PMID- 8430531 TI - Pilot study analysis of the histologic and bacteriologic effects of occlusive dressings in chemosurgical peel using a minipig model. AB - The histologic changes associated with chemosurgery are well documented, but the data concerning the effects of occlusive dressings (adhesive tape, gauze, or ointments) is largely anecdotal. Wide differences of opinion exist as to the best method of phenol application and postpeel wound care regimen. Using a Yucatan minipig as our animal model, we studied the histologic and bacteriologic differences that various commonly used occlusive dressings have upon the initial burn depth and the subsequent healing of peeled skin. We also compared chemical peel with dermabrasion and chemabrasion. Our results showed to statistical difference in peel depth between "wet" versus "moist" phenol application or between occluded versus nonoccluded dressings. Based upon this animal model, we recommend that phenol solutions be applied moist rather than wet and that an occlusive dressing other than adhesive tape be used and maintained for a minimum of four days. PMID- 8430532 TI - Virginal gigantomastia: validity of combined surgical and hormonal treatments. PMID- 8430533 TI - How to deal with abdominoplasty in an abdomen with a scar. AB - Abdominoplasty is a common procedure in plastic surgery. Reviewing 150 patients who underwent abdominoplasty, it has been observed that 72% of the patients already had an abdominal scar. How to deal with abdominoplasty in an abdomen with a previous scar is discussed in this article. PMID- 8430534 TI - Importance of positive interaction in the initial meeting between plastic surgeons and patients: a survey. AB - The aesthetic plastic surgery patient represents a particularly sensitive and highly demanding client within the whole patient population. There is no doubt that a kind and understanding response to his problems and needs, which are often rather complex, contributes decisively to the establishment of a basis of confidence and it predominantly determines the further course of any interpersonal relationship with the surgeon. A kind response, i.e., positive interaction, signifies the complete acceptance of the patient, both verbally and nonverbally. The surgeon must be all ears to the requests and concerns and must attentively concern himself with all the patient's physical impairments that have grown into a problem. Positive interaction also means assessment and understanding of the patient's personality, including his self-image, his view of reality, and his present condition in order to choose correctly the suitable level of communication. Finally, positive interaction means the precise analysis of the patient's rational and irrational fears and his conceptions and expectations. There must be discussion of his wishes and the therapeutic and surgical possibilities in order to map out an acceptable path of treatment. PMID- 8430535 TI - Classification of blepharoplasty. AB - It is well known that one of the most gratifying plastic surgery operations is the correction of baggy eyelids, known as blepharoptosis, blepharochalasis, or a multitude of names given to conditions of the eyelids which mar the beauty of a patient. Even though many techniques have been applied to the variety of conditions that exist in the aging or acquired or hereditarily deformed eyelids, no one has really been able to come up with a definitive classification of deformities of the eyelid because of the many factors involved. Even though we have various names such as blepharoptosis and adiposa cutis laxa, none of these general terms has a good enough definition to give us a complete understanding of what we are to correct on each individual patient. To help classify the complex problem, I try to present a very rough classification of the types of deformity that exist in patients seeking blepharoplasty. The basis of my classification is anatomical factors coupled with the progression of operative techniques from the most simple to the most complex. PMID- 8430536 TI - Sonography of the gravid uterus and placenta: current concepts. AB - Examination of the placenta and gravid uterus is an integral part of any obstetric sonographic study. Fetal well-being and growth depend on an intact uteroplacental vascular supply, and sonography can show most of the macroscopic abnormalities that may adversely affect the placenta or the gravid uterus, and thus compromise the fetus or affect the mode of delivery. The first part of this review will highlight sonography of normal uterine anatomy and pitfalls and review sonographic findings in cases of incompetent cervix, premature labor, and uterine synechiae. The second part will describe some recent advances in sonography of normal placental development and appearance, sonographic and anatomic variations, placental lesions, and implantation abnormalities. PMID- 8430537 TI - Thrombosis and infection caused by thoracic venous catheters: pathogenesis and imaging findings. PMID- 8430538 TI - High-resolution computer display of portable, digital, chest radiographs of adults: suitability for primary interpretation. AB - OBJECTIVE: The suitability of using a high-resolution computer-display system for primary interpretation of adult chest radiographs obtained with portable apparatus and storage phosphor technology was evaluated with receiver operating characteristic analysis and subjective methods. MATERIALS AND METHODS: Sixty portable digital chest radiographs showing abnormalities that approached the resolution limits of our computed radiography system were selected. The original digital data making up the 2140 x 1760 x 10 bit images were transferred to a cathode ray tube (CRT) display system composed of two Megascan monitors. Postprocessing rendered two images, one for each monitor, to emulate the two-on one hard-copy format produced by the computed radiography system. Each image set was interpreted independently by three radiologists experienced with hard-copy format. Limited level and window adjustments were allowed during CRT interpretation. For both CRT and hard-copy display, images were graded on the basis of the interpreter's confidence in the presence of pneumothorax and parenchymal abnormalities. Three types of foreign devices were subjectively analyzed: endotracheal tubes, nasogastric tubes, and temporary epicardial pacer wires. RESULTS: No significant differences were found in detecting pneumothorax or focal infiltrates. One radiologist found the hard copy better for detecting diffuse infiltrates (p = .02); two radiologists favored CRT for visualizing nasogastric tubes (p < .005, p < .02); and one radiologist favored CRT for visualizing temporary epicardial pacer wires (p = .05). CONCLUSION: We conclude that an optimized high-resolution CRT system is quite promising for primary interpretation of digital portable chest radiographs, but further investigation and greater statistical power are necessary to confirm our results. PMID- 8430539 TI - High-resolution CT of the chest: radiation dose. AB - OBJECTIVE: The purpose of this study was to compare the skin radiation dose to the chest produced by high-resolution CT (HRCT) with the radiation dose produced by conventional CT. Previous studies have reported that radiation doses with HRCT are equal to or higher than those with conventional CT. These results, however, were based on the assumption that in HRCT, contiguous sections were scanned without the intersection gaps of 10 or 20 mm that are used clinically. SUBJECTS AND METHODS: We used radiotherapy verification film to measure the skin radiation dose in 56 patients who had chest CT scans. Twenty-two had 1.5-mm collimation HRCT scans at 10-mm intervals, 15 had 1.5-mm collimation HRCT scans at 20-mm intervals, and 19 had 10-mm collimation conventional CT scans at 10-mm intervals. Scan parameters were identical in all cases: 120 kVp, 200 mA, 2 sec. Step wedges were used to generate calibration films with identical beam quality on the CT scanner, and exposure was measured with an ionization chamber. Calibration films and patients' radiotherapy verification films were digitized, and the radiation dose was calculated. RESULTS: Mean skin radiation dose was 4.4 (standard error [SE], 0.2) mGy for 1.5-mm HRCT scans at 10-mm intervals, 2.1 (SE, 0.1) mGy at 20 mm intervals, and 36.3 (SE, 0.9) mGy for conventional 10-mm scans at 10-mm intervals. CONCLUSION: HRCT scanning at 10- and 20-mm intervals produced 12% and 6%, respectively, of the radiation dose associated with conventional CT. This is considerably less radiation than suggested in earlier studies. Combining HRCT scans at 20-mm intervals with low-dose scan (20 mA, 2-sec scans) would result in an average skin dose comparable with the dose administered with chest radiography. PMID- 8430540 TI - A new asymmetric screen-film combination for conventional chest radiography: evaluation in 50 patients. AB - OBJECTIVE: A new asymmetric screen-film combination for conventional chest radiography was evaluated by four thoracic radiologists. MATERIALS AND METHODS: Fifty chest radiographs obtained with a new asymmetric screen-film combination were compared with radiographs obtained in the same patients during the same breath-hold with a conventional system. Patients referred from the oncology service were studied because of the increased prevalence of abnormal findings on chest radiographs in this population. The differences in the quality of the images were assessed by four chest radiologists who used a direct-comparison technique. Eleven anatomic shadows that are normal on chest radiographs were assessed. Fifty abnormal findings also were compared. RESULTS: The image quality of the new asymmetric screen-film combination was judged to be superior to that of the conventional system for normal anatomy and abnormal findings (p < or = .003). CONCLUSION: The new asymmetric film consistently showed more clinically useful detail in the mediastinum and in the lung projected over the diaphragm and heart. The radiation dose was about 30% less with the new screen-film system. PMID- 8430541 TI - Mammographic findings after the removal of breast implants. AB - A recent wave of adverse publicity regarding silicone breast implants has led increasing numbers of women to undergo removal of their implants. In this pictorial essay, we present the spectrum of mammographic findings after implant removal. These range from a nearly normal appearance to architectural distortion and even residual spiculated silicone granulomas that may simulate malignant tumors. Our examples emphasize that comparison with previous mammograms and a detailed surgical history are essential if unnecessary investigations of postsurgical and residual benign abnormalities are to be avoided. PMID- 8430542 TI - How to improve the efficacy of the barium enema examination. PMID- 8430543 TI - Celiac plexus block: efficacy and safety of the anterior approach. AB - OBJECTIVE: A celiac plexus block performed via an anterior approach offers several potential advantages over a posterior approach, including shorter procedure time, less discomfort to the patient, and less risk of neurologic complications. We evaluated the use of an anterior approach to determine its efficacy and safety. MATERIALS AND METHODS: The procedure was performed in 17 consecutive patients referred for treatment of chronic abdominal pain thought clinically to be of celiac ganglion origin. A subjective evaluation of the degree of pain relief was obtained by retrospectively reviewing the notes of physicians and nurses. The degree of pain relief was graded from 1+ (no change) to 4+ (complete relief). An objective evaluation was also obtained by comparing average daily in-hospital analgesic usage before and after the procedure. RESULTS: Ethanol injection was performed successfully in 13 of 14 patients with pancreatic carcinoma and in two of three patients with other causes of pain. Eleven (79%) of the 14 patients with pancreatic carcinoma had some (2+ or greater) relief of pain, and eight of these patients had considerable or complete (3+ or 4+) relief of pain. Of the 10 patients with pancreatic carcinoma for whom complete data on the use of pain medication were available, the mean daily analgesic usage declined from 17% to 100% (mean, 58%) relative to preprocedure doses. Complications, all relatively mild, were encountered in only three of 17 patients, and no patient had neurologic symptoms or long-term sequelae. CONCLUSION: The anterior approach to a celiac plexus block is a safe and effective means of pain control in patients with pancreatic carcinoma. It offers several potential advantages to the posterior approach, and should be considered for all patients with pain caused by pancreatic carcinoma that is refractory to pain medication. PMID- 8430544 TI - Surgical treatment of hepatic metastases: impact of intraoperative sonography. AB - OBJECTIVE: A prospective study was done to determine the influence of intraoperative sonographic findings on surgical decision making in patients with hepatic metastases. SUBJECTS AND METHODS: Thirty-seven consecutive patients with hepatic metastases who underwent surgery (for hepatic resection or intraarterial catheter placement) were prospectively evaluated. For each patient, the resectability of the metastases and the surgical approach were determined preoperatively on the basis of the combined results of sonography, bolus dynamic CT, and CT during arterial portography (CTAP). Those determinations were compared with the decisions made during surgery, which were based on the intraoperative sonographic findings. The surgical procedure that was actually performed was compared with the procedure decided on preoperatively. RESULTS: Eighty-two metastases were surgically and pathologically proved. Preoperatively, 73 (89%) of the 82 metastases were detected with a combination of sonography, bolus dynamic CT, and CTAP. Seventy-nine metastases (96%) were detected with intraoperative sonography. Six metastases in four patients were detected only with intraoperative sonography. Furthermore, in two patients, intraoperative sonography showed four additional metastases, which changed the initial surgical approach decided on preoperatively. CONCLUSION: Our study suggests that intraoperative sonography provides important data that cannot be obtained with preoperative imaging techniques and affect the surgical decision making in patients with hepatic metastases. PMID- 8430545 TI - Mature cystic teratoma of the pancreas: sonographic and CT findings. PMID- 8430546 TI - The role of MR imaging in determining surgical eligibility for pelvic exenteration. AB - OBJECTIVE: The purpose of this study was to evaluate the role of MR imaging in the preoperative assessment of candidates for pelvic exenteration. Specifically, we sought to determine if MR imaging was reliable in selecting patients with pelvic cancer for surgical exenteration. MATERIALS AND METHODS: MR images of the pelvis were retrospectively evaluated in 23 patients with proved pelvic cancer. These images were analyzed for (1) presence and location of the primary or recurrent tumor; (2) tumor extension to the bladder, rectum, or pelvic sidewall; and (3) presence and location of lymphadenopathy. On the basis of the MR findings, we determined suitability for pelvic exenteration by using generally accepted contraindications to surgery (involvement of the pelvic sidewall muscles or metastatic lymphadenopathy). In addition, tumor involvement of the bladder or rectum was evaluated to help determine the type of exenteration indicated. Surgical and/or histologic confirmation was available in all 23 cases. RESULTS: The accuracy of MR imaging in selecting patients was 83% (19 of 23), with a positive predictive value of 56% and a negative predictive value of 100%. In evaluating tumor involvement of the pelvic sidewall and lymph nodes, the negative predictive values were 100% and 95%, respectively. Tumor extension into the pelvic sidewall was overestimated in four patients, in three of whom it was not possible to distinguish radiation changes from tumor on MR images. For assessing extension of these pelvic tumors into the bladder and rectum, MR imaging had an accuracy of 81% and 85%, respectively. CONCLUSION: MR imaging may provide an accurate means of selecting patients considered for pelvic exenteration. MR accurately determined which patients should undergo the surgery, by demonstrating absence of sidewall abnormalities or adenopathy. Radiation changes could not be reliably distinguished from tumor involvement in those patients with sidewall abnormalities, however, especially in the first 6 to 12 months after treatment. PMID- 8430547 TI - Estimating the depth of myometrial involvement by endometrial carcinoma: efficacy of transvaginal sonography vs MR imaging. AB - OBJECTIVE: In this study we compare transvaginal sonography with MR imaging for use in detecting the depth of myometrial involvement by endometrial carcinoma. SUBJECTS AND METHODS: Forty-two consecutive patients with stage I endometrial carcinoma had transvaginal sonography and MR imaging at 0.5 T. All the patients had a hysterectomy within 1-10 days after the imaging studies. The results of histologic examination of the surgical specimen were considered the gold standard of the study. We compared transvaginal sonography and MR imaging for use in assessing myometrial invasion by endometrial carcinoma by means of the staging classification of the International Federation of Gynecology and Obstetrics: stage Ia (tumor limited to endometrium), stage Ib (invasion of less than half the myometrium), stage Ic (invasion of more than half the myometrium). The overdiagnoses and the underdiagnoses for both techniques were calculated. We also evaluated the sensitivity and specificity of the two techniques for assessing the presence of myometrial invasion (stage Ib + stage Ic) and the presence of deep myometrial invasion (stage Ic). The diagnostic indexes evaluated and the differences between them were analyzed by using McNemar's test and 95% confidence intervals. The staging diagnoses based on MR imaging and sonographic findings were compared with staging diagnoses based on histologic examination, and a score was assigned to each diagnosis: these scores were then evaluated with Wilcoxon's signed rank test for paired data. RESULTS: Histologic examination showed that six of the 42 patients had tumor confined to the endometrium (stage Ia), 14 had involvement of the inner half of the myometrium (stage Ib), and 22 had involvement of the outer half of the myometrium (stage Ic). The staging was concordant between the two imaging techniques in 32 cases (concordance, 76%). Among the 10 discordant cases, diagnosis was correct in six cases for MR and four cases for sonography. Overall staging based on sonography was correct with respect to histologic staging in 29 cases (69%; 95% confidence interval, 52-81%). Five tumors (12%) were underdiagnosed and eight (19%) were overdiagnosed. Staging based on MR findings was correct with respect to histologic staging in 31 cases (74%; 95% confidence interval, 58-85%). Five tumors (12%) were underdiagnosed, and six (14%) were overdiagnosed. CONCLUSION: In our experience, there is no difference in the staging diagnoses of transvaginal sonography and MR imaging. Also, concordance with histologic staging diagnoses and sensitivity and specificity indexes did not show statistical differences between the two techniques, although these last results have to be considered with caution because of the low power of the statistical tests. PMID- 8430548 TI - Tubular ectasia of the testicle: sonographic and MR imaging appearance. AB - OBJECTIVE: Ectasia of the seminiferous tubules at the level of the mediastinum is a recently recognized benign condition of the testicles. Although it may have typical sonographic features, the condition can at times be difficult to distinguish from tumors on the basis of sonography. We describe the sonographic and MR appearance of this condition in seven men in whom we were able to distinguish tubular ectasia from tumors of the testicles on the basis of the imaging findings. MATERIALS AND METHODS: Ectasia of the seminiferous tubules was histologically proved in a man who had an intratesticular mass seen on sonograms and MR images. We analyzed the sonographic and MR imaging features in this man and in six others who had similar imaging findings but did not have biopsy proof of tubular ectasia. RESULTS: The first patient was a man with bilateral findings who had a unilateral orchiectomy that revealed ectasia of the seminiferous tubules. Spermatocelectomy was performed in another man whose testis was normal on surgical inspection and on subsequent follow-up. Imaging findings have remained unchanged in one man with 3-year imaging follow-up and in three men with clinical follow-up of 8-22 months. One patient was lost to follow-up. At presentation, most of the men were more than 55 years old. All had a scrotal mass typical of a spermatocele on physical examination, with normal testes when the testes could be palpated. The spermatocele was larger than 4 cm in six of 11 involved epididymides. On imaging, in five of the seven patients, the intratesticular process was bilateral, involved the mediastinum testis, began at the periphery adjacent to the spermatocele, and extended for a variable distance within the testis. On sonograms, the lesion was hypoechoic with coarse internal echoes. MR imaging of six of the seven patients showed characteristic findings and allowed the identification of two additional testicles with tubular ectasia that were missed sonographically. Lesions had a homogeneous signal similar to that of the coexisting spermatocele with all pulse sequences. They were hypointense relative to the testis on T1- and proton density-weighted images and, unlike tumors, were not visible on T2-weighted images. CONCLUSION: Our experience suggests that ectasia of the seminiferous tubules can be distinguished from testicular tumor on the basis of characteristic clinical, sonographic, and MR imaging findings. Thus, orchiectomy is unnecessary to establish the diagnosis and to rule out tumor. PMID- 8430549 TI - Incisional endometrioma involving the rectus abdominis muscle and subcutaneous tissues: CT appearance. PMID- 8430550 TI - Postpartum ovarian vein thrombosis: diagnosis by clot protrusion into the inferior vena cava at sonography. PMID- 8430551 TI - Obstetric and gynecologic radiology: it's time. PMID- 8430552 TI - Diagnosis of meniscal tears of the knee with MR imaging: effect of observer variation and sample size on sensitivity and specificity. AB - OBJECTIVE: A wide range in the efficacy of MR imaging for the diagnosis of meniscal tears of the knee has been reported. To evaluate two possible causes for this variation, we studied how sensitivity and specificity are affected when different observers and sample sizes are used. MATERIALS AND METHODS: Two hundred MR examinations of the knee in patients for whom the results of arthroscopy were available were used for the study. One hundred eight medial meniscal tears and 58 lateral meniscal tears were found at arthroscopy. The sensitivity and specificity for detection of meniscal tears were determined for the original interpretations and retrospective evaluations by three observers. Comparisons were also made between sample sizes of 25 and 100. chi 2 analysis was used for unmatched data sets and McNemar's statistic was used for matched sets. RESULTS: For the 200 examinations, the sensitivity was 0.89-0.93 for medial meniscal tears and 0.79 0.83 for lateral meniscal tears. The specificity was 0.86 for medial meniscal tears and 0.90-0.92 for lateral meniscal tears. Sensitivity and specificity varied widely among different observers and different sample sizes. However, we found no significant difference between any of the comparisons at the p < .05 level. The largest interobserver variation occurred in the detection of lateral meniscal tears, with a sensitivity of 0.71 for one observer and 0.88 for another observer (p = .16). The largest variation between sets of 100 examinations was a change in sensitivity for detection of lateral meniscal tears from 0.74 to 0.88 for the original interpretations (p = .10). For the sample sets of 25 cases, the variation was even larger, with the sensitivity for detection of lateral meniscal tears varying from 0.5 for one set to 1.0 for another. CONCLUSION: We conclude that chance variation related to sample size can cause large but not statistically significant variations in sensitivity and specificity in this setting. These variations are of sufficient magnitude to explain many of the differences in reported sensitivity and specificity for MR imaging in the diagnosis of meniscal tears. We found no significant difference in observer performance. PMID- 8430553 TI - Sonography of the shoulder: evaluation of the subacromial-subdeltoid bursa. AB - The purpose of this essay is to illustrate the sonographic findings in patients with abnormalities of the subacromial-subdeltoid bursa. The anatomy of the subacromial-subdeltoid bursa is complex. This paper illustrates the complexity of the normal bursa and the findings in shoulders with bursal distension. PMID- 8430554 TI - MR imaging of the forefoot: normal anatomic findings. AB - The MR imaging anatomy of the ankle has been well described. The anatomy of the forefoot, however, is not well understood by most radiologists. In many institutions, MR imaging studies are performed by using the head coil with large fields of view so that the appearance of the asymptomatic side can be used for comparison. At our institution, studies of the forefoot are performed with a specialized solenoid coil that allows a field of view of 8 cm with a resultant in plane spatial resolution of approximately 0.3-0.4 mm. In this report, we present the MR imaging anatomy of the normal forefoot. Pertinent osseous, musculotendinous, and neurovascular structures are shown. Particular emphasis is placed on the compartmental anatomy of the foot, which is best imaged in the coronal plane. PMID- 8430555 TI - MR quantification of bone marrow cellularity: use of chemical-shift misregistration artifact. PMID- 8430556 TI - Radiographs of phalangeal fractures: importance of the internally rotated oblique projection for diagnosis. PMID- 8430557 TI - Rectal methohexital for sedation of children during imaging procedures. AB - OBJECTIVE: Brevital (methohexital), administered as a solution per rectum, provides safe, rapid, and effective sedation for induction of surgical anesthesia. This study was undertaken to evaluate rectal Brevital as a sedative for children undergoing imaging procedures. MATERIALS AND METHODS: In a review of patients' records, we found that, during a 1-year period, 190 children from 1 month to 14 years old were sedated for CT or MR imaging. Sedation was required for 94 CT and 96 MR imaging studies. Rectal Brevital was used in 102 patients (mean age, 25 +/- 2 months), and oral chloral hydrate was used in 88 (mean age, 28 +/- 3 months). RESULTS: Sleep was achieved in 81% of patients who received Brevital and in 80% of those who received chloral hydrate. Induction time was shorter (p = .0001) with Brevital (9 +/- 1 min) than with chloral hydrate (28 +/- 2 min). The mean duration of sleep was 46 min with Brevital and 66 min with chloral hydrate (p = .0001). Brevital provided adequate sedation in 89 (87%) of 102 imaging studies, and chloral hydrate did so in 73 (83%) of 88 studies. No cardiorespiratory complications or allergic reactions occurred with either drug. Significantly fewer patients were discharged fully awake and alert after sedation with chloral hydrate than with Brevital (p < .002). Children sedated with chloral hydrate also required a longer period of observation in the radiology department (p < .04). CONCLUSION: We conclude that rectal Brevital produces sedation of adequate duration for most imaging procedures in children. Ease of administration, wide margin of safety, rapid and pleasant induction, and short recovery time make this drug a favorable alternative to other commonly used sedatives. PMID- 8430558 TI - Guidelines for the monitoring and care of children during and after sedation for imaging studies. PMID- 8430559 TI - Normal ovaries in neonates and infants: a sonographic study of 77 patients 1 day to 24 months old. AB - OBJECTIVE: Normal values for ovarian measurements in adults have been revised over the past decade. A recent report stated that ovarian cysts were common in healthy girls 2-13 years old, refuting the findings of a 1984 study. No large sonographic study of normal ovaries in girls 1 day to 24 months old has been performed. We evaluated ovaries in girls in this age group to determine the normal volume and prevalence of ovarian cysts. SUBJECTS AND METHODS: The ovaries of 77 consecutive patients 1 day to 24 months old were evaluated during routine pelvic sonography. Patients were divided into three age groups: 1 day to 3 months old (when gonadotropin levels are highest because of loss of placental hormonal influence), 4-12 months old (an intermediate group), and 13-24 months old (when gonadotropin levels are low). RESULTS: Ninety-eight ovaries were imaged in three dimensions. The mean volume was 1.06 cm3 (range, 0.7-3.6 cm3) among girls up to 3 months old; 1.05 cm3 (range, 0.2-2.7 cm3) among girls 4-12 months old; and 0.67 cm3 (range, 0.1-1.7 cm3) among girls 13-24 months old. We found no significant difference in mean volumes among the three groups. The prevalence of ovarian cysts was similar in all three groups; ovarian cysts were seen in 84% of all imaged ovaries. Macrocysts (cysts larger than 9 mm) were seen in 18% of all cystic ovaries. CONCLUSION: Ovaries of girls 1 day to 24 months old can have volumes greater than 1 cm3. Ovarian cysts are common. Macrocysts can be seen despite claims that they are rare in girls less than 11 years old. PMID- 8430560 TI - Periosteal reaction of the ribs in neonates treated with extracorporeal membrane oxygenation: prevalence and association with soft-tissue swelling. AB - OBJECTIVE: The objectives of the study were to determine the prevalence of periosteal reaction of the ribs in infants treated with extracorporeal membrane oxygenation and to evaluate its association with soft-tissue swelling. MATERIALS AND METHODS: The chest radiographs of 100 consecutive neonates treated with extracorporeal membrane oxygenation were evaluated to determine the maximal soft tissue swelling during therapy and whether periosteal reaction of the ribs developed. The length of extracorporeal membrane oxygenation and the time elapsed before periosteal reaction developed were recorded. The medical records of those with periosteal reaction were reviewed to determine known causes of this condition. The records of a control group of 11 neonates were evaluated in the same manner. RESULTS: Periosteal reaction of the ribs developed in 13 (21%) of the 61 neonates who had less than 11 mm of soft-tissue swelling. In 69% of those with periosteal reaction, the finding first was seen 21-32 days after birth. In the control group, periosteal reaction developed in only one, a neonate who had vibrator chest physiotherapy. CONCLUSION: Periosteal reaction of the ribs in patients treated with extracorporeal membrane oxygenation is associated with soft tissue swelling greater than 11 mm. The periosteal reaction appears to be a self limiting and benign process. PMID- 8430561 TI - The prominent conoid process of the clavicle: a new radiographic sign in Down's syndrome. PMID- 8430562 TI - Assessment of cerebral perfusion by first-pass, dynamic, contrast-enhanced, steady-state free-precession MR imaging: an animal study. AB - OBJECTIVE: The purpose of this study was to determine whether cerebral perfusion could be assessed with a conventional 1.5-T MR imaging system by applying a steady-state free-precession (SSFP) technique during bolus IV injection of contrast material (gadoteridol). Normal and abnormal perfusion states and the effect of the dose of contrast material were studied in cats. MATERIALS AND METHODS: Nine healthy anesthetized cats were imaged after administration of 0.5 mmol/kg (n = 5), 0.25 mmol/kg (n = 2), and 0.1 mmol/kg (n = 2) of gadoteridol. Six cats with an acute infarct of the middle cerebral artery (five cats 10 min after and one cat 1 hr after vessel occlusion) were evaluated at a dose of 0.5 mmol/kg. The middle cerebral artery was ligated in each instance by use of a snare placed around the vessel during surgery, which was performed via a transorbital approach. Each animal was imaged with spin-echo T2-weighted (3000/45,90 [TR/TE]) and T1-weighted (500/10) techniques before contrast material was injected. SSFP images (12/18, 80 degrees tip angle) were acquired sequentially (each with a 1-sec acquisition time and no interimage delay) immediately before and for 45 sec after IV injection of a bolus of gadoteridol. RESULTS: The first-pass effect in both normal gray and white matter was dose dependent, with a greater magnitude of change seen at higher doses of contrast material. A 55% decrease in signal intensity of normal peripheral gray matter was observed during the first pass after bolus injection of 0.5 mmol/kg gadoteridol, compared with a 23% decrease and a 17% decrease at doses of 0.25 and 0.1 mmol/kg, respectively. High temporal (one image per second) and spatial (1.5 x 1.5 x 6.0 mm) resolution was achieved, with sufficient sensitivity that both visual and statistical differentiation of normal and abnormal gray and white matter was possible. Ten minutes after vessel occlusion, the change in signal intensity during the first pass was 45 +/- 5% and 27 +/- 9% for normal central gray and white matter, respectively, as compared with 20 +/- 2% and 11 +/- 5% for ischemic central gray and white matter, respectively. CONCLUSION: Cerebral perfusion can be assessed on conventional 1.5-T MR imaging systems by combining high-dose IV bolus injection of contrast material (in this instance, using gadoteridol) with dynamic SSFP imaging. PMID- 8430563 TI - Aicardi's syndrome: MR appearance of unusual orbital and ventricular cystic lesions. PMID- 8430564 TI - Amyotrophic lateral sclerosis: hyperintensity of the corticospinal tracts on MR images of the spinal cord. PMID- 8430565 TI - Detection of abnormal parathyroid glands in postoperative patients with recurrent hyperparathyroidism: sensitivity of MR imaging. AB - OBJECTIVE: The efficacy of MR imaging in identifying abnormal parathyroid glands in patients with recurrent hyperparathyroidism after surgery was investigated. SUBJECTS AND METHODS: Findings on preoperative T1- and T2-weighted MR images in 44 patients with recurrent hyperparathyroidism were prospectively evaluated and compared with surgical/pathologic results in all patients. A blinded retrospective analysis of the MR findings comparing T1- or T2-weighted images alone and in combination for detection of abnormal parathyroid glands also was performed. RESULTS: Seventy-four percent of surgically proved abnormal parathyroid glands were detected prospectively and 65% were detected retrospectively on MR images. The combination of T1- and T2-weighted images increased the sensitivity for detection. The sensitivity for detection of abnormal glands was 72% in the neck and 86% in the mediastinum. The sensitivities for detecting parathyroid adenomas (80%) and hyperplastic glands (69%) were not significantly different. There was no threshold volume for detection of lesions with MR imaging. Both intrathyroid parathyroid adenomas were missed on MR images. Abnormal glands could not be differentiated from lymph nodes on MR images in three cases. CONCLUSION: MR imaging is a useful technique for detecting abnormal parathyroid glands preoperatively in patients with recurrent hyperparathyroidism after surgery. The combination of T1- and T2-weighted images increases the sensitivity for detection. PMID- 8430566 TI - Intravascular stents: tissue-stent interactions and design considerations. PMID- 8430567 TI - Detection and quantification of carotid artery stenosis: efficacy of various Doppler velocity parameters. AB - OBJECTIVE: The purpose of this study was to evaluate and compare the accuracies of the different Doppler velocity parameters used to grade stenoses of the carotid artery. MATERIALS AND METHODS: Seven velocity parameters determined with Doppler spectra were compared with angiographic findings in 138 carotid bifurcations: the peak systolic and peak end-diastolic velocities in the internal and common carotid arteries, the ratios of peak systolic and peak end-diastolic velocities between the internal and common carotid arteries, and the ratio of peak systolic velocity in the internal carotid artery to peak end-diastolic velocity in the common carotid artery. A receiver-operating-characteristic (ROC) analysis was performed, with and without correction for the bias introduced by preferentially selecting patients for angiography, if the Doppler results indicated a lesion. Multiple regression analysis was performed to predict the percent stenosis and to predict the probability of a 70% or greater stenosis. RESULTS: Of the Doppler parameters, the peak systolic velocity in the internal carotid artery and its ratio to the peak end-diastolic velocity in the common carotid artery were the most accurate and had equivalent test performance (ROC area = 0.94; after correction for verification bias, ROC area = 0.78). In multiple regression analysis, the peak systolic velocity in the internal carotid artery was the most significant parameter, although its ratio to the peak end diastolic velocity in the common carotid artery had incremental value in detecting a 70% or greater stenosis, and the peak systolic velocity in the common carotid artery provided additional information for quantifying the stenosis. CONCLUSION: The peak systolic velocity in the internal carotid artery is the best single velocity parameter for quantifying a stenosis and for detecting a 70% or greater stenosis. PMID- 8430568 TI - Morphologic and hemodynamic findings at sonography before and after creation of a transjugular intrahepatic portosystemic shunt. AB - OBJECTIVE: The purpose of this study was to describe the morphologic and hemodynamic findings in the hepatic vasculature before and immediately after creation of a transjugular intrahepatic portosystemic shunt. SUBJECTS AND METHODS: We used gray-scale, duplex, and color Doppler sonography to prospectively examine 25 patients before and after percutaneous placement of a stent to create a transjugular intrahepatic portosystemic shunt. Patency and direction of flow were determined in the stent and in the main, right, and left portal veins. Flow velocity was measured in the stent and in the main portal vein. RESULTS: In all patients, the stent was easily identified as connecting branches of the portal and hepatic veins. Three thrombosed stents were correctly detected sonographically. One stent that was thought to be thrombosed at sonography was found to be patent at angiography. Flow velocities in the patent stents ranged from 73 to 185 cm/sec (mean, 130 +/- 33 cm/sec). Mean peak velocities in the main portal vein were 20 cm/sec before stent placement and 38 cm/sec after stent placement (p < .002). In 14 patients, flow direction in the left or right portal vein was hepatofugal after the stent was placed. In two of these 14 patients, long-term follow-up showed subsequent conversion of flow in the portal vein branches from hepatofugal to hepatopetal. One of these two patients had a thrombosed stent and the other had a hepatic vein stenosis above the stent. The second patient also had a proven decrease in flow velocity in the stent at the time of stenosis. CONCLUSION: We conclude that high flow velocities are expected in the main portal vein and in the stent immediately after the shunt is created and that flow in portal vein branches is usually hepatofugal. We recommend sonography soon after the shunt is created, so that baseline flow velocity in the stent and flow direction in portal vein branches can be established, because a subsequent decrease in flow velocity in the stent or a change in direction of flow in a portal branch may indicate stent malfunction. PMID- 8430569 TI - Balloon angioplasty above the aortic arch: immediate and long-term results. AB - OBJECTIVE: Angioplasty above the level of the aortic arch is becoming more common, and the indications for it are increasing. We report our experience with this procedure, including life-table analysis of the long-term results. MATERIALS AND METHODS: We dilated 32 lesions in 29 patients. Early in our series, patients were referred primarily because of arm claudication or vertebrobasilar insufficiency. Subsequently, the indications were expanded to include inflow to left internal mammary-coronary artery bypass grafts, inflow to axillobifemoral bypass grafts, and inflow to dialysis fistulas in the upper extremity. A femoral artery approach was used in 18 patients and an axillary approach was used in 11. Clinical follow-up included evaluation of symptoms and bilateral measurements of peripheral pulses and blood pressure. Follow-up angiograms were obtained in nine patients. RESULTS: Eighteen of the lesions dilated were located in the left subclavian artery, eight were in the right subclavian artery, four were in the axillary or proximal brachial artery, and two were in the innominate artery. Interestingly, three of eight right subclavian arteries treated had an anomalous origin from the arch of the aorta. Initial technical success was 100%. All 29 patients had long-term follow-up of 4-88 months (mean, 36 months). In one patient, stenosis recurred 8 months after angioplasty. This patient subsequently had redilatation. Life-table analysis projected a 7.5-year cumulative primary patency rate of 96.6%. No cerebrovascular complications or embolic events occurred. CONCLUSION: Angioplasty of the great vessels is safe and effective, and the long-term results are favorable when compared with results after surgery. As a result, the indications for this procedure should be broadened. PMID- 8430570 TI - Contrast material for combined abdominal and pelvic CT: can cost be reduced by increasing the concentration and decreasing the volume? AB - OBJECTIVE: The purpose of this study was to determine if enhancement provided by a smaller volume of a more concentrated nonionic contrast agent is equivalent to that provided by a larger volume of a less concentrated nonionic agent on dynamic, incremental abdominal and pelvic CT. SUBJECTS AND METHODS: During a 4 month period, 168 patients undergoing dynamic incremental abdominal and pelvic CT received 150 ml iopamidol-300 (45 g iodine). During the following 4 months, 119 patients received 125 ml ioversol-320 (40 g iodine). The same automated injector and scanning parameters were used for both groups. Absolute enhancement of the liver at three levels and of abdominal and pelvic vessels was calculated and analyzed by using Student's t-test. RESULTS: Arterial and venous enhancement in the upper part of the abdomen, at the level of the iliac crest, or in the pelvis was not significantly different with the two contrast agents. Both ioversol and iopamidol provided the same mean enhancement of the hepatic parenchyma at the level of the hepatic veins (45 H) and at the level of the portal vein (49 H). At the level of the gallbladder fossa, enhancement of liver parenchyma with the two contrast agents was significantly different (p = .04): mean enhancement was 45 H for iopamidol and 42 H for ioversol. A retrospective analysis of the liver enhancement profiles from 50 randomly selected patients from each group showed no significant difference in parenchymal enhancement. CONCLUSION: For dynamic abdominal and pelvic CT, no statistically significant difference was found between the mean enhancement of the liver and abdominal vessels after administration of 125 ml of ioversol-320 and that after administration of 150 ml of iopamidol-300. Therefore, 125 ml of ioversol-320 can be used instead of 150 ml of iopamidol-300 without compromising image quality. At current prices, this will result in savings of approximately 18% per patient. PMID- 8430571 TI - Investigation of contrast enhancement in CT of the liver: the need for improved methods. PMID- 8430572 TI - Early contributions of medical students, interns, and residents to the development of radiology. PMID- 8430573 TI - Radiology summit meeting 1992: the role of radiology in health care reform. PMID- 8430574 TI - Severe adverse reaction to iv gadopentetate dimeglumine. PMID- 8430575 TI - Unchained images: another problem for the radiologist. PMID- 8430576 TI - Mammography: positive predictive value and true-positive biopsy rate. PMID- 8430577 TI - AIDS-related lymphoma: an unusual cause of omental caking. PMID- 8430578 TI - Seat-belt injury of the abdominal aorta. PMID- 8430579 TI - Where is the organ of Zuckerkandl? PMID- 8430580 TI - Primary uterine lymphoma: MR imaging. PMID- 8430581 TI - Fetus papyraceus. PMID- 8430582 TI - Tuberculous arthritis of the knee: MR findings. PMID- 8430583 TI - Pachydermoperiostosis involving the skull and spine: MR findings. PMID- 8430584 TI - Infrarenal atherosclerotic aortic web. PMID- 8430585 TI - Large-bore guide catheters facilitate road mapping with microcatheters. PMID- 8430586 TI - Occult glove perforations. PMID- 8430587 TI - Primary care: an idea in search of a paradigm? PMID- 8430588 TI - Family physicians and sex education. PMID- 8430589 TI - Family physicians and sex education. PMID- 8430590 TI - Beyond smoking cessation. PMID- 8430591 TI - This is progress? PMID- 8430592 TI - Current uses of total parenteral nutrition. AB - Total parenteral nutrition has become a well-established intervention for the following indications: to sustain life in patients with short-bowel syndrome; for perioperative use in nutritionally deprived patients; to improve quality of life for patients with inflammatory bowel diseases; to assist the healing of enterocutaneous and pancreatic fistulas; for supportive care in patients with acute pancreatitis; as an adjunct to therapy in patients with acute renal or hepatic failure; for hypermetabolic states such as sepsis, trauma, burns and acquired immunodeficiency syndrome; in neonatal and pediatric patients; in transplantation recipients, including bone marrow, renal, cardiac and liver transplants; for precoronary artery bypass graft myocardial glycogen loading; in the field of obstetrics; to enhance survival in patients with closed head injuries; to treat life-threatening anorexia nervosa; in patients with cystic fibrosis and for nutritional support in home use. PMID- 8430593 TI - Interpreting the mammogram report. AB - The standardization of imaging techniques, interpretation and reporting has become an important issue as the use of mammographic screening has increased. Each mammogram report should indicate whether the breast is fatty or consists of dense glandular tissue. A brief description of abnormalities should be followed by the conclusion and recommendations. Well-circumscribed lesions have a 98 percent benign rate; these lesions generally do not require biopsy but can be followed at six-month intervals for a period of time. The overall rate of malignancy for biopsies prompted by mammography is 20 to 35 percent. Lesions interpreted as highly suspicious are malignant in 75 to 90 percent of cases. Mammographically detected tumors are generally smaller than palpable tumors at the time of diagnosis. In addition, patients who have mammographically detected lesions are more often node-negative and therefore have a better prognosis than patients with palpable lesions. PMID- 8430594 TI - Respiratory distress syndrome in the newborn: innovative therapies. AB - Neonatal respiratory distress syndrome affects 60,000 to 70,000 infants each year in the United States. Although the mortality rate has decreased dramatically over the past 30 years, many infants die or have sequelae from the syndrome. Three innovative techniques are now playing a role in improving the course of neonates with respiratory distress syndrome: surfactant replacement therapy, high frequency ventilation and extracorporeal membrane oxygenation. Surfactant therapy should be considered the standard of care for infants with respiratory distress syndrome who require mechanical ventilation. Further investigation is needed to define the precise roles of high-frequency ventilation and extracorporeal membrane oxygenation in the management of neonates with respiratory distress syndrome. PMID- 8430595 TI - Endovascular surgery for peripheral arterial occlusive disease. AB - Endovascular surgery includes angiography, balloon angioplasty, laser angioplasty, mechanical atherectomy and stent placement. Both diagnostic and therapeutic procedures are possible. The advantages of endovascular techniques include the ability to precisely and noninvasively remove an atherosclerotic lesion without producing damage to the surrounding vascular wall. Endovascular techniques have minimal complications, involve minimal blood loss and can be performed as outpatient procedures. Drawbacks include disappointingly high rates of restenosis, limitations on the type of lesion that can be treated successfully and only partial visualization of an atherosclerotic lesion with some devices. PMID- 8430596 TI - Nonpharmacologic aids in the treatment of depression. AB - While pharmacotherapy is often necessary to effectively treat depression, many depressed patients do not fully respond to, or will not cooperate with, medication trials. Nonpharmacologic interventions such as patient and family education, self-help efforts, cognitive therapy, family involvement and behavioral scheduling may, in various combinations, provide either primary or adjunctive treatment for mild to moderate depression. Family physicians can adapt these techniques to the primary care setting. Recent changes in the economic climate as it affects the availability of psychiatric care have magnified the role of primary care physicians in the treatment of depression. PMID- 8430597 TI - Adult intussusception. AB - Intussusception occurs when one segment of bowel telescopes into an adjacent segment, resulting in obstruction and possible ischemic injury. The disorder is rare in adults. Most cases of adult intussusception have a demonstrable lead point. Benign and malignant tumors are the cause of intussusception in nearly two thirds of adult cases. The diagnosis is often elusive because of the vague, chronic nature of the clinical presentation. Symptoms are usually suggestive of intermittent, partial intestinal obstruction. Barium studies or computed tomographic scans can be helpful in making the diagnosis. Surgery is required because of the high incidence of underlying pathology. PMID- 8430598 TI - Advances in the prevention, diagnosis and treatment of deep venous thrombosis. AB - Deep venous thrombosis of the leg is associated with hospitalization in up to 600,000 Americans each year. Prevention is possible; the preventive strategy varies according to the degree of risk. Noninvasive techniques, especially impedance plethysmography, have revolutionized the diagnosis of deep venous thrombosis and should be the diagnostic methods of first choice. Patients with suspected calf vein thrombi but negative impedance plethysmography studies need not receive anticoagulation therapy as long as serial studies remain negative. Five days of intravenous heparin constitutes adequate treatment, and warfarin can be initiated on the first day of heparin therapy. Intravenous heparin will most likely be replaced by the subcutaneous, low-molecular-weight form once it becomes widely available. Bleeding is the principal side effect of anticoagulation therapy; careful attention to pharmacokinetics and pharmacodynamics can minimize this side effect. Use of the prothrombin time international normalized ratio allows safer, more reproducible anticoagulation with oral agents. PMID- 8430599 TI - Fifth Joint National Committee report on high blood pressure. PMID- 8430600 TI - Pharmacologic characteristics of a new calcium antagonist, manidipine: beneficial effects on renal circulation and vascular changes. AB - The calcium antagonist, manidipine, was developed on the basis of the hypothesis that antihypertensive drugs that act to improve renal hemodynamic alterations will be therapeutically beneficial in hypertensive patients. Manidipine shows long-lasting calcium channel-blocking action in vascular smooth muscle cells and antihypertensive actions in various types of hypertensive models. The drug has high selectivity for resistance vessels, dilates renal vasculature, and inhibits renal vascular constrictions induced by norepinephrine and angiotensin II in spontaneously hypertensive rats. It increases renal blood flow and has a prominent natriuretic action without changing glomerular filtration rate. The coronary dilating effect of the drug is similar to that of nifedipine, but its cardiodepressant effects are less potent than those of other dihydropyridines. Furthermore, manidipine prevents the development of cerebrovascular lesions and inhibits the progression of vascular damage in the brain and kidneys of stroke prone spontaneously hypertensive rats. The drug also inhibits a proliferative response of the intima to balloon catheter-induced injury in the carotid arteries of spontaneously diabetic rats without affecting plasma lipids or blood pressure. These results suggest that manidipine may be useful for the treatment of hypertensive patients with or without vascular complications. PMID- 8430601 TI - Protective effects of calcium antagonists in different organs and tissues. AB - The therapeutic efficacy of calcium antagonists in ischemic disorders of various tissues is attributed to vasodilator and antivasoconstrictor activities. A direct, energy-conserving, antiischemic effect of certain calcium antagonists has been claimed repeatedly by basic scientists. The clinical value of such effects has been doubtful until recently, when the organ-protective activity of certain calcium antagonists was confirmed in a few large-controlled clinical trials. The following evidence has been presented for the protective activity of calcium antagonists: (1) for the heart, beneficial effects of verapamil and diltiazem have been shown on reinfarction and mortality rates, (2) relative to the brain, the beneficial effect of nimodipine has been shown in preventing neurologic deficits after subarachnoidal hemorrhage, and an antimigraine effect of flunarizine has been demonstrated, (3) concerning the blood vessels, israpidine and lacidipine have been demonstrated to have antiatherogenic potency in animal models, and (4) for the kidneys, an antivasoconstrictor effect occurs at the preglomerular level. In addition, verapamil, diltiazem, and nitrendipine may protect against radiocontrast-induced nephrotoxicity, and verapamil counteracts cyclosporine nephrotoxicity. PMID- 8430602 TI - Effects of manidipine and other calcium antagonists on rat renal arcuate arteries. AB - We investigated the effect of 1,4-dihydropyridine calcium antagonists (nifedipine, nisoldipine, and manidipine) on serotonin (5-hydroxytryptamine [5 HT])- and KCl (120 mmol/L)-induced contractions of rat isolated renal arcuate arteries. The preparation showed the well-known biphasic response to KCl-induced depolarization. All three calcium antagonists were more potent in inhibiting the second phase (tonic) compared with the first phase (transient) of the effect. The inhibitory concentration of 50% (pIC50) values were 6.92 +/- 0.24/8.51 +/- 0.08 (nifedipine, n = 32), 7.61 +/- 0.10/9.33 +/- 0.03 (nisoldipine, n = 28), and 7.61 +/- 0.13/9.07 +/- 0.06 (manidipine, n = 32) for the suppression of the first and second phases, respectively. In small coronary and renal arteries maximally activated with KCl solution, nifedipine and manidipine concentrations dependently inhibited the calcium concentration response curves. Manidipine was more potent than nifedipine (pIC50 coronary artery: 9.26 +/- 0.14 vs 7.93 +/- 0.22; pIC50 renal artery: 9.14 +/- 0.14 vs 7.77 +/- 0.21), but both compounds showed the same potency in the two different preparations. Furthermore, the influence of the calcium antagonists on the 5-HT concentration-response curve was investigated. Marked differences were found in the ability of the three compounds to inhibit the 5-HT-induced vasoconstriction of isolated renal arteries. For manidipine, a 93% +/- 3% reduction of the maximal 5-HT-induced contraction was observed, which was a significantly stronger inhibition compared with nifedipine (43% +/- 4.12%) or nisoldipine (26% +/- 0.37%). The pIC50 values were 7.96 +/- 0.15 (nifedipine), 8.17 +/- 0.14 (nisoldipine), and 7.84 +/- 0.12 (manidipine).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430603 TI - Effect of calcium antagonist, manidipine hydrochloride, on renal hemodynamics and tubuloglomerular feedback in spontaneously hypertensive rats. AB - The effects of a calcium antagonist, manidipine, on renal hemodynamics and the tubuloglomerular feedback (TGF) mechanism were examined in 7- to 8-week-old spontaneously hypertensive rats (SHRs) and age-matched normotensive Wistar-Kyoto rats (WKYs). Manidipine, 10 micrograms/kg intravenously, reduced blood pressure only in SHRs. A greater increase in renal plasma flow occurred in SHRs, but effects on GFR were observed in both SHR and WKY rats. Filtration fraction decreased only in SHRs. The TGF response curve in SHRs was shifted to the left compared with that in WKY rats, indicating a more active TGF in hypertensive rats. Manidipine infusion produced a right and upward shift of the feedback curve in SHRs and only an upward shift in WKY rats. We conclude that manidipine corrects hyperactivity of the TGF mechanism in SHRs. PMID- 8430604 TI - Manidipine affects rPDGF-BB-induced gene transcription of low-density lipoprotein receptors and 3-hydroxy-3-methylglutaryl coenzyme A reductase in human mesangial cells. AB - The effects of manidipine, a newly developed Ca2+ channel blocker, on recombinant platelet-derived growth factor BB (rPDGF-BB)-induced transcription of the low density lipoprotein receptor and the 3-hydroxy-3-methylglutaryl coenzyme A reductase genes in human mesangial cells are reported. The transcription of the rPDGF-BB-induced gene of the low-density lipoprotein receptor was enhanced and maintained over a longer period, whereas the transcription of the 3-hydroxy-3 methylglutaryl reductase gene was blocked by manidipine at nanomolar concentrations. The results suggest that aside from the ability to block manidipine's potential-operated Ca2+ channels, manidipine also affects gene transcription of relevant proteins involved in the regulation of cholesterol metabolism at concentrations close to those efficacious for clinical therapies. This may further explain the antiinflammatory and organ-protective activities of the compound. PMID- 8430605 TI - Hypertension and the kidney: determinants of the response to antihypertensive therapy and their implications. AB - Medicine has long recognized an association between hypertension and the kidney. The kidney may be a culprit or a victim in the process. As a culprit, the kidney may be responsible for the pathogenesis of hypertension in many patients, and in virtually all patients the renal response to antihypertensive therapy is a major determinant of its success or failure. In some patients, hypertension can lead to renal injury and even end-stage renal disease. Indeed, 25% of patients entering dialysis or transplant programs in the United States today have hypertension as the primary or sole mechanism, and another 25% have the complex combination of diabetes and hypertension as the cause. Antihypertensive therapy appears to be successful in preventing or arresting the renal response in accelerated hypertension, regardless of the treatment used to reduce blood pressure. However, treatment appears to be less successful in preventing the progression of moderate hypertension to end-stage renal disease. Substantial evidence suggests that angiotensin-converting enzyme inhibition and calcium channel blockade may prevent this progression when other antihypertensive therapy does not. The renal response to an angiotensin-converting enzyme inhibitor or a calcium channel-blocking agent appears to be determined by the pathogenetic features of the hypertension, and this may be an important determinant of the efficacy of the agents selected. Although still indistinct, the guidelines favoring selection of a specific antihypertensive agent are gradually emerging. PMID- 8430606 TI - Studies on the glomerular microcirculatory actions of manidipine and its modulation of the systemic and renal effects of endothelin. AB - We examined the actions of intravenously administered manidipine on systemic and renal microcirculatory hemodynamics and its efficacy in antagonizing endothelin-1 (ET-1)-evoked responses. Manidipine was a potent vasodilator with preferential activity in the renal vasculature. Its administration in optimal doses resulted in decreases in systemic arterial pressures accompanied by increases in renal perfusion and filtration rates. Its primary sites of action in the kidney were at both pre- and postglomerular arteriolar sites. Manidipine was capable of near total reversal of the sustained elevations in arterial pressure and the progressive reductions in renal blood flow and glomerular filtration rates induced by intravenously administered ET-1. In the presence of prolonged calcium channel blockade, subsequent administration of ET-1 led to paradoxic hypotensive responses, which could be profound and blocked by an inhibitor of nitric oxide synthesis. These unexpected vasorelaxant actions of ET-1 in the presence of manidipine were likely caused by the dual effects of antagonism of its own intrinsic vasoconstrictor action (through calcium channel blockade), as well as ET-1-evoked release of the endothelium-derived relaxing factor, nitric oxide. PMID- 8430607 TI - An evaluation of the renal protective effect of manidipine in the uninephrectomized spontaneously hypertensive rat. AB - The effects of calcium antagonism on the development and progression of renal disease are controversial. To address this problem, studies were performed on young, uninephrectomized spontaneously hypertensive rats (SHRs) with the dihydropyridine calcium antagonist, manidipine, to assess its effect on the early pathogenesis of focal glomerulosclerosis. Male SHRs underwent uninephrectomy at age 10 to 11 weeks and were subsequently assigned to no treatment (control), a predetermined subvasodepressor (low) dose of manidipine (2.5 mg/kg body weight), or a predetermined antihypertensive (high) dose of manidipine (20 mg/kg body weight). All animals received a diet containing 0.4% sodium and 23% protein. Serial determinations of body weight, systolic tail cuff pressure, and 24-hour urinary excretion of creatinine, sodium, and protein (UprotV) were made at 1- to 6-week intervals, for a total treatment period of 12 weeks. In final experiments plasma was obtained for creatinine, angiotensin I, and angiotensin II determinations, and renal tissue was harvested for histologic and morphometric analysis. Compared with the untreated control, low-dose manidipine therapy had no effect on body weight, systolic blood pressure, creatinine clearance, UprotV, renal histologic findings, glomerular volume, or plasma angiotensin I or II concentrations. In contrast, high-dose manidipine therapy decreased systolic blood pressure from 194 +/- 3 to 160 +/- 4 mm Hg (p < 0.01). Creatinine clearance and UprotV were unchanged. Although body weight was not different, kidney weight was higher. However, mean glomerular volume was lower. More importantly, the prevalence of mesangial expansion with proliferation was lower: 6.7% (control) versus 2.8% (high-dose manidipine) (p < 0.01). Finally, plasma angiotensin I and angiotensin II concentrations did not differ.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430608 TI - The antiatherosclerotic effect of the calcium antagonists and their implications in hypertension. AB - Calcium-dependent processes involved in atherosclerotic lesion formation include platelet aggregation, monocyte adhesion, release of growth factors, cell proliferation and migration, protein and collagen secretion and synthesis, and endothelial necrosis. In addition, the calcium (Ca2+) component of smooth muscle cell contraction contributes to one of the main risk factors, hypertension. The ability of the calcium channel blockers (CCBs) to interrupt the sequence of events that culminates in the formation of atherosclerotic lesions has been demonstrated in animal models and clinical trials. These studies have involved the short-acting CCBs. The results of this animal study show that manidipine, a new long-acting CCB, produces a dose-dependent reduction in atherosclerotic lesion formation without reducing plasma cholesterol. PMID- 8430609 TI - Efficacy of manidipine in the treatment of hypertension with renal impairment: a multicenter trial. AB - The effects of 5 to 20 mg/day of manidipine, a dihydropyridine-type calcium channel blocker, on blood pressure and renal function were studied in 71 hypertensive patients with renal impairment (serum creatinine levels between 1.4 and 5 mg/dl). Thirty-two patients were followed for more than 48 weeks, and 22 patients remain on the treatment after 24 to 48 weeks. The study was interrupted in 17 patients. In 32 patients who were followed for more than 48 weeks, blood pressure was well controlled in 21 (65.6%) patients. In seven of these patients alpha beta- or beta-blockers were added to manidipine to control blood pressure. Only 1 of 32 patients whose serum creatinine level was below 3.1 mg/dl showed deterioration of renal function during the 48 weeks. Two of the 17 patients in whom the study was interrupted died of cerebral bleeding or pneumonia. Two patients discontinued the study because of complications of myocardial infarction and retinal infarction, six withdrew because of deterioration in renal function, and the other seven patients withdrew because of poor compliance. From these studies, it was concluded that manidipine is well tolerated and effective in hypertensive patients with renal impairment (serum creatinine levels < or = 3 mg/dl). If blood pressure is not well controlled in these patients, combined treatment with manidipine and alpha beta- or beta-blockers is recommended. PMID- 8430610 TI - Efficacy and mode of action of manidipine: a new calcium antagonist. AB - Clinical studies were performed on patients with mild-to-moderate essential hypertension to elucidate the efficacy and mode of action of manidipine. Augmentation of diuresis and natriuresis during the short- and long-term phases of manidipine treatment was found in essential hypertensive patients. Manidipine partly inhibited sympathetic nerve activity and suppressed the mean arterial pressure response to infused norepinephrine. This drug also inhibited aldosterone secretion. Natriuresis and suppression of pressor responses may contribute to the depressor mechanisms of this drug. After manidipine administration, increases in both urinary calcium and uric acid were observed. Both parameters were positively correlated with urinary excretion of sodium, and the inhibition of tubular reabsorption may contribute to this mechanism. The increase in plasma parathyroid hormone may also be involved in the calciuresis produced by manidipine. Patients with lower plasma renin activity or lower plasma ionized calcium levels showed a greater reduction in blood pressure after manidipine administration. Thus the hypotensive action of manidipine was more pronounced in low renin essential hypertension. PMID- 8430611 TI - Calcium antagonists in the treatment of arterial hypertension. AB - Calcium antagonists are widely used antihypertensive agents whose hemodynamic effects consist of a reduction in blood pressure and peripheral vascular resistance that is associated, in case of short-term administration, with a reflex increase in heart rate and cardiac output. These compounds exert several additional positive effects besides blood pressure reduction. Among them, calcium antagonists exert their antihypertensive effect without negatively interfering with both central and reflex neural control of circulation. The only change in baroreflex function observed during the administration of these compounds is a resetting of the baroreflex toward the lower blood pressure values achieved by treatment. New calcium antagonists of the dihydropyridine type are characterized by a greater vascular selectivity, and by the ability to exert a persistent blood pressure reduction throughout the 24 hours when administered in a single oral dose. The latter feature can be properly assessed by means of ambulatory blood pressure monitoring techniques. PMID- 8430612 TI - Trademark similarities can cause problems. PMID- 8430613 TI - Selecting OTC products for coughs and colds. AB - The cold season offers many opportunities for the pharmacist to help patients select appropriate products. Actively exercising this opportunity can bring professional satisfaction and strengthen the pharmacist-patient bond. PMID- 8430614 TI - What you need to know about OBRA '90. PMID- 8430616 TI - Election 1992: what it might mean for pharmacy. PMID- 8430615 TI - Update on otitis media. Part 2. Treatment. AB - Currently the treatment of choice for OM is an oral antimicrobial agent, but selecting a specific agent should include consideration of efficacy, adverse effect profile, compliance, and cost. The use of adjunctive medications like decongestants for specific subtypes of OM has been debated in the literature, but efficacy has not been proven. As knowledge about the pathogenesis of OM is further refined, new treatment modalities for OM will be introduced. Because pharmacists are involved daily with pediatric patients who experience OM, they have an important role in making sure that patients receive appropriate therapy. A patient's profile should be checked for allergies and concurrent medications when a prescription for an antimicrobial agent is presented for a child with OM. The parents should be counseled about the administration, storage, and general product use as well as potential adverse effects, duration of use, and the need for compliance. An administration device for drug delivery like an oral syringe should be provided. Parents need advice from the pharmacist in making sure their children receive the best possible pharmaceutical care. PMID- 8430617 TI - Pharmacoeconomics: an emerging role for pharmacists. PMID- 8430619 TI - Reflections on a pharmacy hot line. PMID- 8430618 TI - New antibacterial agents. AB - These seven agents offer wider choices in drug regimens, and the use of certain agents should improve patient compliance because of less frequent dosing and shorter duration of treatment. Treatment indications can be expected to expand as additional studies are conducted. PMID- 8430621 TI - Implementing a self-care-consulting practice. PMID- 8430620 TI - Use of psychoactive medications in children and adolescents. PMID- 8430622 TI - Primary coronary angioplasty for acute myocardial infarction with contraindication to thrombolysis. AB - Patients with acute myocardial infarction (AMI) and contraindication to thrombolysis have a high mortality and morbidity with conventional medical treatment. Among 226 consecutive patients hospitalized within 6 hours of the onset of Q-wave AMI, 45 (20%) had contraindications to thrombolysis. All were treated by emergent primary angioplasty. Mean age of the 45 patients was 60 +/- 11 years and 8 (18%) were > or = 70 years old; 17 (38%) had multivessel disease and 5 (11%) presented with cardiogenic shock. Successful angioplasty was achieved in 42 of the 45 patients (93%) 52 +/- 27 minutes after admission and 238 +/- 100 minutes after the onset of pain. Overall in-hospital mortality was 9% (4 of 45). Neither major bleeding nor stroke occurred. There was 1 case of early symptomatic reocclusion, treated with emergent repeat angioplasty without reinfarction. Predischarge angiography in 33 patients showed only 1 silent reocclusion (3%). Ejection fraction at discharge was 46 +/- 13%. Repeat catheterization at 6 months in 19 patients showed 4 restenoses (21%) and 4 reocclusions (21%) of the infarct related artery. There were 3 late deaths (2 noncardiac), which gave survival rates of 87 and 85% at 1 and 3 years, respectively, and event-free survival rates of 71 and 69% including in-hospital deaths. There were no cases of late reinfarction. Consequently, in this series, primary coronary angioplasty proved safe and highly effective in rapidly restoring sustained infarct-vessel patency during AMI, and led to a greater improvement in early and late outcomes than that reported in the literature for medically treated subjects in this high-risk subset for which thrombolytic therapy is contraindicated. PMID- 8430623 TI - Results of percutaneous transluminal coronary angioplasty of either the left anterior descending or left circumflex coronary artery in patients with chronic total occlusion of the right coronary artery. AB - The acute and long-term results of percutaneous transluminal coronary angioplasty (PTCA) of the left coronary artery in 106 patients (group 1) with chronic occlusion of the right coronary artery were compared with those of 106 patients matched for sex (92 male) and age (56 +/- 10 years) undergoing left PTCA with a normal right coronary artery (group 2). Before the procedure, group 1 had more unstable angina (42 vs 29%; p < 0.05), more frequent prior myocardial infarction (80 vs 25%; p < 0.001), and a lower left ventricular ejection fraction (56 +/- 10% vs 65 +/- 11%; p < 0.005). Acute results were not different in the 2 groups with respect to primary success (group 1: 93%; and group 2: 89%) and complications (group 1: 2 with emergency coronary surgery, and 4 with periprocedural myocardial infarction and no death; and group 2: 1 with emergency coronary surgery, 1 death, and 3 with periprocedural myocardial infarction). At 6 months, 79 patients in group 1 and 71 patients in group 2 had reangiography; the rate of restenosis was 35% in group 1 and 42% in group 2. In both groups, left ventricular ejection fraction increased significantly in patients without restenosis (58 +/- 12% vs 63 +/- 10%, p < 0.001 [n = 44] in group 1; and 66 +/- 9% vs 70 +/- 10%, p < 0.001 [n = 29] in group 2). In group 1, improvement was significant only for patients without collaterals to the occluded right coronary artery (59 +/- 10% vs 66 +/- 7%; p < 0.003 [n = 24]).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430624 TI - Myocardial infarct artery patency and reocclusion rates after treatment with duteplase at the dose used in the International Study of Infarct Survival-3. Burroughs Wellcome Study Group. AB - Duteplase, 98% double-chain recombinant tissue-type plasminogen activator, was administered intravenously in 488 patients with acute myocardial infarction in a multicenter, open, safety and patency study. Duteplase dosing was based on body weight. Duteplase was administered as a bolus of 0.04 MIU/kg of thrombolytic activity followed by 0.36 MIU/kg over 1 hour and 0.067 MIU/kg/hour for 3 additional hours. The patency rate of the infarct-related artery at 90 minutes was 69% (330 of 478). The reocclusion rate at 3 to 48 hours was 6% (18 of 301). Reinfarction occurred in 7.6% of patients (37 of 488), but 12 reinfarctions occurred after coronary angioplasty. Serious bleeding occurred in 7.6% of patients (37 of 488), predominantly at the catheterization entry site. There were 3 instances of central nervous system bleeding, 1 fatal. Fibrinogen levels declined to 83% of baseline at 24 hours. Weight-based dosing may explain the low incidence of serious bleeding in this study. The in-hospital mortality was 6.6% (32 of 488). This study documents that the dose of duteplase used in the International Study of Infarct Survival-3 results in a 90-minute coronary artery patency rate and safety profile comparable to those reported in published studies on the approved dose of alteplase. PMID- 8430625 TI - Design and baseline results of the Scandinavian Simvastatin Survival Study of patients with stable angina and/or previous myocardial infarction. AB - The Scandinavian Simvastatin Survival Study is a clinical trial of patients with coronary artery disease (CAD) and mild or moderate hypercholesterolemia. The primary objective is to investigate whether long-term treatment with the serum lipid-lowering agent simvastatin in patients with serum total cholesterol levels between 5.5 and 8.0 mmol/liter (212 to 309 mg/dl) will reduce overall mortality. The secondary objective is to investigate whether simvastatin treatment reduces the incidence of major CAD events (fatal and nonfatal myocardial infarction and sudden death). This is a multicenter, randomized, double-blind, placebo controlled clinical trial. Patients of both sexes, aged 35 to 69 years, with stable angina pectoris or previous myocardial infarction were recruited at 94 clinical centers throughout Scandinavia. Dietary advice was given to 7,027 patients who were followed for 2 months. Of these, 4,444 met the eligibility criteria and were subsequently randomized to receive simvastatin or similar placebo tablets. The patients will be followed for a minimum of 3 years and until total mortality reaches 440 deaths. This report presents certain design features of this study such as methods of recruitment and follow-up of patients, adjustment procedures for the test drug dose, sample size and power calculations, and organization of the study. Baseline results are summarized and ethical aspects of the study are also discussed. PMID- 8430626 TI - Detection of viable tissue in healed infarcted myocardium by dipyridamole thallium-201 reinjection and regional wall motion studies. AB - Reinjection imaging with thallium-201 (Tl-201) may provide a convenient method of assessing myocardial viability. Twenty patients with a previous Q-wave healed myocardial infarction were examined to evaluate the detection of viable tissue in infarcted segments. All patients underwent to evaluate the detection of viable tissue in infarcted segments. All patients underwent dipyridamole Tl-201 tomographic imaging with reinjection of 1 mCi of Tl-201 after redistribution. Radionuclide ventriculography was performed before and after administration of 5 mg of dinitrate isosorbide sublingually for regional wall motion analysis. Patients presented with 38 fixed defects, 12 of which demonstrated improved Tl 201 uptake on reinjection; 10 of 12 reinjection-reversible segments were hypokinetic or normal after administration of nitrates, whereas 22 of 26 nonreversible segments remained akinetic or dyskinetic (p < 0.001). Of 20 patients, 9 had reinjection-reversible segments; coronary angiography revealed a patent infarct-related artery or collaterals, or both, in 7 of these patients. The infarct-related artery was patent or collaterals were present, or both, in 4 of 11 patients who did not improve with reinjection. It is concluded that reinjection of Tl-201 during dipyridamole Tl-201 scintigraphy may frequently detect viable tissue in infarcted segments in patients with a Q-wave infarction. Segments with reinjection reversibility usually do not remain dyskinetic or akinetic after administration of nitrates and have some residual flow on coronary angiography. PMID- 8430627 TI - Comparison of the electrophysiologic effects of oral sustained-release and intravenous verapamil in patients with paroxysmal supraventricular tachycardia. AB - The electrophysiologic effects of intravenous verapamil (0.15 mg/kg) and oral sustained-release verapamil (verapamil-SR) (240 mg once daily for 7 days) were studied in 17 patients with paroxysmal supraventricular tachycardia (SVT). Ten patients had atrioventricular (AV) nodal reentrant tachycardia and 7 had AV reciprocating tachycardia involving an accessory AV pathway. Both preparations significantly prolonged anterograde effective refractory period of the AV node and depressed the retrograde AV nodal conduction system. The sinus cycle length, and atrial and ventricular effective refractory periods were prolonged after oral verapamil-SR. Furthermore, oral verapamil-SR depressed retrograde accessory pathway conduction which was not interfered with by intravenous verapamil. Intravenous verapamil and oral verapamil-SR prevented induction of sustained SVT in 12 of 17 (71%) and 10 of 17 (59%) patients, respectively. Follow-up study with oral verapamil-SR 240 mg once daily in 15 patients for 19 +/- 6 months revealed that among the 8 patients without induction of sustained SVT, 7 have been free of symptomatic arrhythmia; only 1 patient had occasional SVT attacks. For the 7 patients with induction of sustained SVT, 3 patients failed to respond to oral verapamil-SR, 1 patient became symptom free, and the remaining 3 patients had less frequent SVT attacks. Thus, immediate intravenous verapamil testing predicts the electrophysiologic results of oral verapamil-SR therapy, and oral verapamil SR once daily may be used for long-term prophylaxis of SVT with better patient compliance. PMID- 8430628 TI - Comparison of left ventricular function in insulin- and non-insulin-dependent diabetes mellitus. AB - Diabetes mellitus has been reported to have controversial effects on left ventricular (LV) function in patients with no evidence of coronary artery disease. In this study, LV function at rest was evaluated in 2 groups of diabetic patients, with insulin-dependent (IDD; n = 16) and non-insulin-dependent (NIDD; n = 23) diabetes mellitus, with no evidence of coronary artery disease. All patients underwent an electrocardiographic stress test, and first-pass and equilibrium radionuclide angiography at rest and during supine exercise. Data in each group of diabetic patients were compared with those obtained from age- and sex-matched normal subjects. In both groups of diabetic patients plasma catecholamine levels were significantly greater than in control subjects. Ejection fraction at rest and during exercise did not differ between each group of diabetic patients and their respective control group. In patients with IDD, peak ejection rate (4 +/- 1 end-diastolic count/s) was significantly greater than in control subjects (2.6 +/- 0.1 end-diastolic count/s; p < 0.001); similarly, peak filling rate (4.3 +/- 1.0 end-diastolic count/s) was significantly greater than in controls (3.0 +/- 0.2 end-diastolic count/s; p < 0.001). Cardiac output and systemic vascular resistances did not differ between patients with IDD and control subjects. In contrast, patients with NIDD had significantly reduced cardiac output compared with that of control subjects (5.7 +/- 0.2 vs 5.9 +/- 0.2 liter/min; p < 0.01), and increased systemic vascular resistances (1,422 +/- 137 vs 1,314 +/- 68 dynes.s.cm-5; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430629 TI - Is atrial pacing needed for determination of coronary flow reserve by parametric imaging? AB - Heart rate changes during determination of coronary flow by parametric imaging may influence the flow measurement. Thus, the question is whether atrial pacing is mandatory for determination of coronary flow reserve (CFR) by this technique. CFR was calculated by digital subtraction angiography (parametric imaging) in 10 patients (8 with coronary artery disease and 2 control subjects) during sinus rhythm and during atrial pacing. Flow measurements were determined in the perfusion region of the left anterior descending and circumflex coronary artery, both at rest and after maximal coronary vasodilation with 10 mg intracoronary papaverine. CFR was defined as coronary flow during hyperemia divided by coronary flow at rest. Spontaneous heart rate was 71 +/- 15 min-1 at baseline, 73 +/- 15 min-1 after papaverine injection and 85 +/- 10 min-1 during atrial pacing. Heart rate variations during coronary arteriography were 4 +/- 3 min-1 at baseline and 5 +/- 4 min-1 after papaverine administration. CFR was 2.61 +/- 1.01 during sinus rhythm and 2.67 +/- 1.05 during atrial pacing. Mean absolute difference in CFR between sinus rhythm and atrial pacing was 0.31 +/- 0.31 (12 +/- 10% of CFR during pacing). Spontaneous heart rate variations during coronary arteriography are not associated with significant changes in CFR. Thus, atrial pacing is not mandatory for the determination of CFR by parametric imaging. PMID- 8430630 TI - Hemodynamic and angiographic comparison of intravenous nitroglycerin and nicardipine mainly in subjects without coronary artery disease. AB - Twenty patients were studied during cardiac catheterization to compare hemodynamic and quantitative angiographic effects of intravenous nicardipine and nitroglycerin. After baseline measurements, nicardipine or nitroglycerin was administered by randomized continuous infusion beginning at 10 micrograms/min titrated to achieve a 10 to 12% reduction in systemic arterial pressure. Hemodynamic measurements and angiography were then repeated. Nicardipine did not change heart rate, and a small decrease (82 +/- 4 vs 75 +/- 4 beats/min) was observed with nitroglycerin, whereas mean arterial pressure decreased similarly ( 11%) in both groups. Nicardipine increased (+13%) and nitroglycerin decreased ( 21%) cardiac output. Although both drugs were associated with significant reductions in pulmonary artery wedge and pulmonary artery pressures, changes were greater with nitroglycerin for pulmonary artery wedge (-49% vs -26%) and pulmonary artery (-39% vs -13%) pressures, whereas only nitroglycerin reduced right atrial pressure significantly. Neither drug altered left ventricular ejection fraction or pulmonary vascular resistance, and only nicardipine decreased systemic vascular resistance significantly. Quantitative coronary angiography (videodensitometry) showed dilation of the left main, proximal, mid and distal anterior descending and circumflex segments by both nitroglycerin and nicardipine. Nicardipine dilated small (< 2 mm2) and large (> 2) arterial segments equally, whereas nitroglycerin showed a proportionately greater effect on small vessels. PMID- 8430631 TI - Strokes, statistics and sophistry in trials of thrombolysis for acute myocardial infarction. PMID- 8430632 TI - Comparison of thrombolysis in myocardial infarction perfusion grades 2 and 3 after anterior wall infarction. PMID- 8430633 TI - Screening for latent coronary artery disease by fluoroscopic detection of calcium in the coronary arteries. PMID- 8430634 TI - Rotational coronary atherectomy of ostial stenoses. PMID- 8430635 TI - Investigational use of the Palmaz-Schatz biliary stent in large saphenous vein grafts. PMID- 8430636 TI - Differences in norepinephrine levels in different vascular beds in congestive heart failure. PMID- 8430637 TI - Frequency of left ventricular dysfunction and other echocardiographic abnormalities in human immunodeficiency virus seronegative intravenous drug users. PMID- 8430638 TI - Endothelin-1 in primary pulmonary hypertension and the Eisenmenger syndrome. PMID- 8430639 TI - Comparison of exercise and adenosine technetium-99m sestamibi myocardial scintigraphy for diagnosis of coronary artery disease in patients with left bundle branch block. PMID- 8430640 TI - The onset of symptomatic atrial fibrillation and paroxysmal supraventricular tachycardia is characterized by different circadian rhythms. PMID- 8430641 TI - Morphologic patterns in patients undergoing reoperation after repair of rheumatic mitral regurgitation. PMID- 8430642 TI - Prevalence of mitral valve prolapse in morbid obesity. PMID- 8430643 TI - Anterograde balloon valvuloplasty of aortic stenosis in children. PMID- 8430644 TI - Accurate detection of elevated left ventricular filling pressure by a simplified bedside application of the Valsalva maneuver. PMID- 8430645 TI - Effect of subadipose tissue on the variables of signal-averaged electrocardiography in healthy subjects. PMID- 8430646 TI - Alcoholic beverage choice and risk of coronary artery disease mortality: do red wine drinkers fare best? PMID- 8430647 TI - On the value of the activated clotting time for monitoring heparin therapy in acute coronary syndromes. PMID- 8430648 TI - Effects of radiofrequency ablation of supraventricular reentrant tachycardia on left ventricular systolic dysfunction. PMID- 8430649 TI - Evaluation of possible long-term adverse consequences of radiofrequency ablation of accessory pathways. PMID- 8430650 TI - Prolonged survival (74 years) in unoperated tetralogy of Fallot with associated mitral valve prolapse. PMID- 8430651 TI - Combined treatment of mitral regurgitation and atrial fibrillation with valvuloplasty and the Maze procedure. PMID- 8430652 TI - Amounts of coronary arterial luminal narrowing and composition of the material causing the narrowing in Buerger's disease. PMID- 8430653 TI - Granular cell tumor of the sinus node. PMID- 8430654 TI - Anterior-inferior myocardial infarction. PMID- 8430655 TI - Myocardial contusion during boxing. PMID- 8430656 TI - Antihypertensives and glucose intolerance. PMID- 8430657 TI - Acute myocardial infarction triggered by emotional stress. PMID- 8430658 TI - Peripheral vascular angioplasty. PMID- 8430659 TI - Normal sinus rhythm. PMID- 8430660 TI - Silent coronary artery disease in patients to undergo carotid endarterectomy. PMID- 8430661 TI - Echocardiography of left ventricular trabeculations, bands and false tendons. PMID- 8430662 TI - Avoid the phrase electrocardiographic "changes". PMID- 8430663 TI - Mental stress and the left ventricular ejection fraction. PMID- 8430664 TI - Reversible cardiomyopathy due to thyrotoxicosis. PMID- 8430665 TI - Death in opera and hereditary prolongation of the Q-T interval. PMID- 8430666 TI - Drainage of pericardial fluid. PMID- 8430667 TI - Lack of uniform hemodynamic changes during exercise in hypertrophic cardiomyopathy. PMID- 8430669 TI - Vitamin C, cholesterol, and the nutritional recommendations. PMID- 8430668 TI - Intravenous amiodarone for conversion of recent-onset atrial fibrillation to sinus rhythm. PMID- 8430670 TI - Adjusting the QT interval for heart rate. PMID- 8430671 TI - Asymptomatic cardiac ischemia pilot study (ACIP). Correction. PMID- 8430672 TI - Malnutrition in hemodialysis patients. AB - Increasing attention has been paid recently to the problem of protein and energy malnutrition and its effects on mortality and morbidity in hemodialysis (HD) patients. Protein deficiency has received more attention than other nutritional problems, largely because its consequences are more easily measured and large population studies have demonstrated the adverse effects of even small decreases in serum albumin on patient's survival. This review discusses these findings and presents other indicators of early malnutrition, which range from static measurements of plasma constituents such as transferrin and insulin-like growth factor 1 (IGF-1), kinetic measurements of protein catabolic rate (PCR) derived from urea kinetic modeling, and noninvasive measurements of body composition. In addition, the predialytic and dialytic factors that influence nutritional status, including the adverse effects of uremia, inadequate dialysis, membrane bioincompatibility, and intercurrent illness requiring hospitalization, as well as socioeconomic factors, are discussed. While some of these are difficult to deal with, the review emphasizes simple interventions that are likely to benefit the patient, including the delivery of optimal dialysis, appropriate choice of medications, and dietary interventions. Once malnutrition is established, parenteral nutrition may reverse the objective evidence of malnutrition, but its effects on survival have not yet been documented. Finally, the review addresses the effects of therapeutic substances such as growth hormone (GH) and erythropoietin (EPO) in combination with nutrients that at present appear to be favorable but are still being evaluated. PMID- 8430673 TI - Serum albumin concentration-related Health Care Financing Administration quality assurance criterion is method-dependent: revision is necessary. AB - The objective of this study was to examine quantitative differences between the two commonly used methods for determining serum albumin concentration, bromcresol green (BCG) and bromcresol purple (BCP), in normal subjects and in 235 unselected dialysis patients in view of recently established Health Care Financing Administration (HCFA) quality assurance review criteria. The mean of normal results by the BCG method was 4.4 g/dL, and 97.5% of values were 3.8 g/dL or higher. The mean of normal results by the BCP method was 3.9 g/dL, and 97.5% of values were 3.3 g/dL or higher. Serum albumin concentrations in samples from the dialysis patients had respectively lower mean values by both methods. For the BCG method, the mean was 3.8 g/dL, and 82% of values were 3.5 g/dL or higher; for the BCP method, the mean was 3.3 g/dL, and 82% of values were 3.0 g/dL or higher. Likewise, for the reference immunonephelometric procedure, the mean value for the dialysis patients was 3.3 g/dL, and 82% of values were 3.0 g/dL or higher. For the samples from the dialysis patients, in comparison with the immunonephelometric method, the BCG method exhibited both constant (intercept = 9.3 g/L) and proportional error (slope = 0.87). The mean albumin value for the BCG method was 3.8 g/dL, 15% higher. In contrast, the BCP method compared closely with the reference method: slope = 1.00, intercept = 0.8 g/L, mean x = 3.3 g/dL, mean y = 3.3 g/dL. The HCFA quality assurance criteria are valid only for the BCG method.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430674 TI - Growth hormone-induced glomerular hyperfiltration is dependent on vasodilating prostanoids. AB - Exogenous growth hormone (GH) and insulin-like growth factor (IGF)-I induce an increase of renal hemodynamics in normal subjects, but the precise mechanism mediating this phenomenon has not been explored in humans. We investigated whether the renal response to exogenous GH requires the presence of vasodilating prostaglandins (PG). In 10 healthy normotensive women with normal renal function, the effect of recombinant human (rh)GH on glomerular filtration rate (GFR) was examined using an intraindividual cross-over design. The subjects were studied under conditions of normal hydration and controlled sodium and protein intake without and with coadministration of indomethacin, 150 mg/d. rhGH, 4.5 IU twice per day, was administered by subcutaneous self-injection for 3 days. GFR was measured as inulin clearance (Cin) in the morning hours in the fasting state in supine position before and after 3 days of rhGH treatment. Baseline GFR was 115.7 +/- 10.1 (SD) mL/min/1.73 m2. Three days of treatment with rhGH caused a 50% increase in serum IGF-I values and GFR increased by 10% to 127.9 +/- 11.7 mL/min/1.73 m2 (P < 0.03). The study was repeated under coadministration of indomethacin, which was started 2 days before application of rhGH. Despite a similar increase in serum IGF-I values, the increase in GFR was completely blocked by indomethacin. Urinary PGE2 excretion was not stimulated by rhGH, but decreased by 50% during indomethacin treatment, as expected. These findings suggest that the increase of GFR during GH treatment in humans is mediated by or requires the presence of vasodilating prostanoids. PMID- 8430675 TI - Kaliuretic response to aldosterone: influence of the content of potassium in the diet. AB - The excretion of potassium (K+) decreased by 50% (30 v 63 mEq/d, P < .01) when subjects consumed a diet that was low in K+ for 3 days. Although part of this conservation of K+ was achieved in part by suppressing the release of aldosterone, nevertheless providing exogenous mineralocorticoids did not lead to a large kaliuresis when there was a modest degree of K+ depletion. Accordingly, the purpose of this study was to evaluate possible mechanisms for this antikaliuretic response to mineralocorticoids. The renal handling of K+ was examined by independent analysis of the two factors that influence its excretion, the driving force to secrete K+ and the urine volume. This driving force is reflected in a noninvasive fashion by the transtubular [K+] gradient (TTKG). Stimuli to increase the rate of excretion of K+ in subjects on a normal and a low K+ diet included the administration of 200 micrograms fludrocortisone (9 alpha F), the induction of a high urine flow rate (9 alpha F+furosemide), the induction of bicarbonaturia (9 alpha F+acetazolamide), and the excretion of Cl(-)-poor urine (< 15 mEq/L). On the low-K+ diet, the peak value for the TTKG 3 to 4 hours after 9 alpha F was less than half that while on the normal diet (6.4 v 14, P < 0.01). In contrast, the TTKG was not significantly different on either diet when there was bicarbonaturia or the excretion of a Cl(-)-poor urine (18 v 17 and 17 v 16, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430676 TI - Clinical correlates of functional status in patients with chronic renal insufficiency. AB - Patients with end-stage renal disease (ESRD) are known to have significantly reduced functional abilities, as measured by the Sickness Impact Profile (SIP). We investigated the clinical correlates with SIP scores in a cohort of patients with lesser degrees of renal dysfunction recruited from an academic general medicine practice (mean calculated creatinine clearance, 25 mL/min). Of 603 eligible patients with chronic renal insufficiency (CRI) defined as a serum creatinine greater than 1.5 mg/dL and a calculated creatinine clearance less than 50 mL/min on two occasions more than 6 months apart, 360 (60%) agreed to participate. These patients were primarily elderly (mean age, 69 years) black (83%), women (69.2%), with an average of 6 years of education and a household income of $400 to $800 per month; 92% had hypertension and 57% had diabetes. The SIP was administered in-home by trained interviewers. Independent variables included demographic data, education, income, and medications (via interviewers), vital signs taken by a renal nurse, and diagnostic test results and diagnoses from patient's computerized records. The total SIP score was the dependent variable, and its physical and psychosocial subscales were also investigated. Variables with univariate correlations with total SIP (P < 0.05) were included in a multiple regression analysis. All variables with a multivariable P value less than 0.10 were included in the final model. The mean SIP score was 24.5 +/- 15.6, higher than that found in patients on dialysis. Significant (P < 0.05) independent correlates with higher SIP scores (greater disability) were lower educational level and income, prior diagnoses of coronary artery disease and stroke, and lower serum albumin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430677 TI - Hypomagnesemic hypocalcemia in chronic renal failure. AB - Hypomagnesemic hypocalcemia in chronic renal disease is a rare finding. Controversy remains regarding the role of decreased magnesium in producing impaired parathyroid hormone (PTH) secretion versus target organ unresponsiveness to PTH. We describe six patients with severe chronic renal disease in whom hypocalcemia and hypomagnesemia were detected. Five patients had chronic interstitial nephropathy; all of them showed renal magnesium wasting. One patient had chronic glomerulonephritis and a malabsorption syndrome and showed a low rate of urinary excretion of magnesium. The administration of magnesium increased calcium levels in all patients. We have found elevated PTH levels in absolute terms, which, however, were inappropriate to correct hypocalcemia; the PTH levels increased in three patients and not in the other three after magnesium replacement. We conclude that in patients with tubulointerstitial nephropathies, chronic renal losses of magnesium can produce hypomagnesemic hypocalcemia. PMID- 8430678 TI - Comparison of imipenem pharmacokinetics in patients with acute or chronic renal failure treated with continuous hemofiltration. AB - The total clearance of imipenem, a carbapenem antibiotic, is reduced from approximately 230 mL/min in patients with normal renal function to approximately 50 mL/min in patients with chronic renal failure. This decline in clearance results not only from the loss of renal clearance, but also from a reduction in the nonrenal clearance from 130 to 50 mL/min. Current dosing recommendations for the administration of imipenem to patients with acute or chronic renal failure are based on this reduced clearance rate. We investigated the pharmacokinetics of imipenem in critically ill patients with acute or chronic renal failure to determine whether published dosing guidelines were applicable to both patient populations. Imipenem pharmacokinetic parameters were determined in 10 anuric patients with renal failure managed by continuous venovenous hemofiltration (CVVH). Seven patients had acute renal failure, while the other three had preexisting chronic renal failure. Imipenem serum concentration data were incorporated into a first-order, single-compartment pharmacokinetic model. Determinations of the area under the serum concentration-time curve were made by the trapezoidal rule. Dosing regimens were calculated from clearance data to achieve a mid-dose imipenem serum concentration of 12 mg/L. The total clearance of imipenem in patients with acute renal failure (108.3 +/- 13.8 mL/min; mean +/- SD) was significantly greater than the total clearance measured in patients with chronic renal failure (64.4 +/- 10.5 mL/min; P < 0.02). This increased clearance resulted from a greater nonrenal clearance of the drug in patients with acute renal failure (95.0 +/- 13.8 v 51.1 +/- 10.5 mL/min; P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430679 TI - Occurrence of pyuria and bacteriuria in asymptomatic hemodialysis patients. AB - Patients with end-stage renal disease on hemodialysis have documented defects in their immune responses, and infections contribute significantly to their morbidity and mortality. This study prospectively detected and quantitated leukocyturia and bacteriuria in asymptomatic hemodialysis patients. Thirty-one percent of asymptomatic hemodialysis patients had significant pyuria (> 10 white blood cells per high-power field) and 25% had bacteriuria of pathologic dimensions, (> 1 x 10(5)/mL of a single microorganism). Pyuria was a good marker for significant bacteriuria in these patients. These results demonstrate that the urinary tract, even in ESRD patients on hemodialysis, may represent a significant reservoir for infection. PMID- 8430680 TI - Effect of continuous ambulatory peritoneal dialysis on blood pressure control. AB - To assess the efficacy of blood pressure control in continuous ambulatory peritoneal dialysis (CAPD), blood pressure was examined sequentially in 63 CAPD patients transferred from hemodialysis (HD), and in 97 patients started de novo on CAPD (NEW), over periods ranging from 3 to 63 months. Blood pressure changes were related to changes in body weight, hematocrit, and treatment with recombinant human erythropoietin (rHu-EPO), as well as to changes in antihypertensive drug requirements. Both groups of patients showed an immediate improvement in blood pressure control at 1 month, as manifested by an absolute decrease in blood pressure in HD patients (-4.3% +/- 2.1% [SEM], P < 0.05) and by a decrease in antihypertensive drug requirements in NEW patients (from 78% to 43.3%). This early improvement in blood pressure appeared to be volume-related, as reflected by changes in body weight. Both groups showed an additional decrement in blood pressure at approximately 6 months (-7.8% +/- 2.6% [SEM], P < 0.05, HD group; -3.4% +/- 2.4% [SEM], P < 0.05, NEW group). Treatment of anemia with rHu-EPO in 22 of the CAPD patients had no effect on blood pressure. CAPD thus appears to be more effective than HD in controlling blood pressure. PMID- 8430681 TI - A controlled, double-blind, randomized trial of verapamil and cyclosporine in cadaver renal transplant patients. AB - Calcium channel blockers have immunomodulating effects in vitro and may be effective in preventing cyclosporine nephrotoxicity. We studied the effect of verapamil following renal transplantation on the incidence of rejection and cyclosporine nephrotoxicity in a double-blind, placebo-controlled trial. Patients were randomly assigned to placebo (n = 28) or verapamil (n = 32) at doses of 80 mg twice a day. There was no difference in the incidence of rejection or cyclosporine toxicity in the two study arms. Recipients randomized to verapamil had lower mean cyclosporine doses at all intervals during a 1-year follow-up. Although cyclosporine doses were lower in the placebo group, the mean cyclosporine levels were equivalent in the two groups. Recipients in the verapamil-treated group had a higher mean serum creatinine at the end of the study--1.7 mg/dL versus 1.4 mg/dL in the placebo group. Actual 1-year graft survival was 89% for the placebo recipients versus 91% in the verapamil-treatment group. When compared with placebo, the concomitant use of low-dose verapamil results in lower cyclosporine doses but equivalent cyclosporine blood levels. Reduction in the incidence of rejection or cyclosporine nephrotoxicity were not observed. PMID- 8430682 TI - Budd-Chiari syndrome in autosomal dominant polycystic kidney disease: a complication of nephrectomy in patients with liver cysts. AB - We report two patients with autosomal dominant polycystic kidney disease (ADPKD) who developed the Budd-Chiari syndrome following bilateral nephrectomy. Both patients had massive cystic enlargement of the liver. Neither had any other identifiable risk factors for the Budd-Chiari syndrome. We suggest that removal of the kidneys may predispose toward anatomic obstruction of the inferior vena cava or hepatic veins by liver cysts. Nephrectomy should be approached cautiously in ADPKD patients with extensive involvement of the liver by cysts. PMID- 8430683 TI - Transient exercise-induced water intoxication and rhabdomyolysis. AB - Water loading only rarely results in adverse effects due to the high efficiency of the kidney in excreting free water. However, when renal diluting ability is impaired, such as in inappropriate vasopressin secretion, water intoxication can occur in otherwise normal individuals. We report the case of a 19-year-old man with acute voluntary water intoxication following exercise, which resulted in a transient defect in renal diluting capability. Hyponatremia was further complicated by rhabdomyolysis. We review the literature regarding other cases of hyponatremia following excessive water intake, and discuss the possible association between hyponatremia and rhabdomyolysis. We conclude that monitoring of muscle enzymes is indicated in acute hyponatremia, to allow for timely intervention intended to prevent rhabdomyolysis-associated acute renal failure. PMID- 8430684 TI - Immune-mediated type A gastritis and glomerulonephritis. AB - The first two cases reported in the literature of patients with immune-mediated type A gastritis with microcarcinoids (as part of a polyglandular syndrome type II in one) in combination with chronic glomerulonephritis are presented. Immune mediated type A gastritis appears to be another immunologic disorder that can be associated with chronic glomerulonephritis. PMID- 8430686 TI - National Kidney Foundation Dialysis Technician Task Force. PMID- 8430685 TI - Resistance to erythropoietin: immunohemolytic anemia induced by residual formaldehyde in dialyzers. AB - Because of inadequate renal synthesis of erythropoietin, the anemia associated with chronic renal failure has been treated successfully in most patients on hemodialysis with recombinant human erythropoietin. Hemolysis due to anti-Nform antibody in dialysis patients with the reused dialyzer may be one of the factors that cause refractoriness to erythropoietin therapy. Patients who do not respond to erythropoietin administration should be screened for anti-Nform antibody. PMID- 8430687 TI - Looking upon the water. Diet Coke floats, but Classic Coke sinks. PMID- 8430688 TI - Human immunodeficiency virus infection and glomerular disease. PMID- 8430689 TI - ESRD treatment incidence versus ESRD incidence. PMID- 8430690 TI - Total body nitrogen by neutron activation in maintenance dialysis. PMID- 8430691 TI - Rubinstein-Taybi syndrome caused by submicroscopic deletions within 16p13.3. AB - The Rubinstein-Taybi syndrome (RTS) is a well-defined complex of congenital malformations characterized by facial abnormalities, broad thumbs and big toes, and mental retardation. The breakpoint of two distinct reciprocal translocations occurring in patients with a clinical diagnosis of RTS was located to the same interval on chromosome 16, between the cosmids N2 and RT1, in band 16p13.3. By using two-color fluorescence in situ hybridization, the signal from RT1 was found to be missing from one chromosome 16 in 6 of 24 patients with RTS. The parents of five of these patients did not show a deletion of RT1, indicating a de novo rearrangement. RTS is caused by submicroscopic interstitial deletions within 16p13.3 in approximately 25% of the patients. The detection of microdeletions will allow the objective conformation of the clinical diagnosis in new patients and provides an excellent tool for the isolation of the gene causally related to the syndrome. PMID- 8430692 TI - Deletion at chromosome 16p13.3 as a cause of Rubinstein-Taybi syndrome: clinical aspects. AB - In the accompanying paper, a chromosomal localization of the Rubinstein-Taybi syndrome by cytogenetic investigations with fluorescence in situ hybridization techniques at chromosome 16p13.3 is described. We investigated 19 of these patients and their parents (a) to ascertain the parental origin of the chromosome with the deletion in families where such a deletion was detected, (b) to disclose whether uniparental disomy plays a role in etiology, and (c) to compare clinical features in patients with a deletion to those in individuals in whom deletions were not detectable. Molecular studies showed a copy of chromosome 16 from each parent in all 19 patients. Uniparental disomy was also excluded for five other chromosome arms known to be imprinted in mice. None of the probes used for determining the origin of the deleted chromosome proved to be informative. The clinical features were essentially the same in patients with and without visible deletion, with a possible exception for the incidence of microcephaly, angulation of thumbs and halluces, and partial duplication of the halluces. A small deletion at 16p13.3 may be found in some patients with Rubinstein-Taybi syndrome. Cytogenetically undetectable deletions, point mutations, mosaicism, heterogeneity, or phenocopy by a nongenetic cause are the most probable explanations for the absence of cytogenetic or molecular abnormalities in other patients with Rubinstein-Taybi syndrome. PMID- 8430693 TI - Match probabilities in racially admixed populations. AB - The calculation of match probabilities is the most contentious issue dividing prosecution and defense experts in the forensic applications of DNA fingerprinting. In particular, defense experts question the applicability of the population genetic laws of Hardy-Weinberg and linkage equilibrium to racially admixed American populations. Linkage equilibrium justifies the product rule for computing match probabilities across loci. The present paper suggests a method of bounding match probabilities that depends on modeling gene descent from ancestral populations to contemporary populations under the assumptions of Hardy-Weinberg and linkage equilibrium only in the ancestral populations. Although these bounds are conservative from the defendant's perspective, they should be small enough in practice to satisfy prosecutors. PMID- 8430694 TI - Linkage localization of X-linked Charcot-Marie-Tooth disease. AB - Charcot-Marie-Tooth disease (CMT), also known as hereditary motor and sensory neuropathy, is a heterogeneous group of slowly progressive, degenerative disorders of peripheral nerve. X-linked CMT (CMTX) (McKusick 302800), a subdivision of type I, or demyelinating, CMT is an X-linked dominant condition with variable penetrance. Previous linkage analysis using RFLPs demonstrated linkage to markers on the proximal long and short arms of the X chromosome, with the more likely localization on the proximal long arm of the X chromosome. Available variable simple-sequence repeats (VSSRs) broaden the possibilities for linkage analysis. This paper presents new linkage data and recombination analysis derived from work with four VSSR markers--AR, PGKP1, DXS453, and DXYS1X--in addition to analysis using RFLP markers described elsewhere. These studies localize the CMTX gene to the proximal Xq segment between PGKP1 (Xq11.2-12) and DXS72 (Xq21.1), with a combined maximum multipoint lod score of 15.3 at DXS453 (theta = 0). PMID- 8430695 TI - Autosomal dominant retinitis pigmentosa: no evidence for nonallelic genetic heterogeneity on 3q. AB - Since the initial report of linkage of autosomal dominant retinitis pigmentosa (adRP) to the long arm of chromosome 3, several mutations in the gene encoding rhodopsin, which also maps to 3q, have been reported in adRP pedigrees. However, there has been some discussion as to the possibility of a second adRP locus on 3q. This suggestion has important diagnostic and research implications and must raise doubts about the usefulness of linked markers for reliable diagnosis of RP patients. In order to address this issue we have performed an admixture test (A test) on 10 D3S47-linked adRP pedigrees and have found a likelihood ratio of heterogeneity versus homogeneity of 4.90. We performed a second A-test, combining the data from all families with known rhodopsin mutations. In this test we obtained a reduced likelihood ratio of heterogeneity versus homogeneity, of 1.0. On the basis of these statistical analyses we have found no significant support for two adRP loci on chromosome 3q. Furthermore, using 40 CEPH families, we have localized the rhodopsin gene to the D3S47-D3S20 interval, with a maximum lod score (Zm) of 20 and have found that the order qter-D3S47-rhodopsin-D3S20-cen is significantly more likely than any other order. In addition, we have mapped (Zm = 30) the microsatellite marker D3S621 relative to other loci in this region of the genome. PMID- 8430696 TI - Distribution of lod scores under uncertain mode of inheritance. AB - We consider probability distributions of alternative lod statistics, differing in their treatment of segregation parameters when mode of inheritance is uncertain. A particular pedigree structure and a dominant genetic system displaying incomplete penetrance are analyzed. Lod scores calculated assuming an incorrect segregation model appear to conform quite well to the chi 2 distribution in the absence of linkage. In the presence of linkage, some power is lost. However, if lod scores are calculated under several different segregation models and the best one is accepted, opportunity for chance occurrence of high lod scores is enhanced. The distribution is still chi 2, but with extra degrees of freedom. These results hold over a wide range of sample sizes and segregation models, including small samples and low levels of penetrance. PMID- 8430697 TI - Asymptotic properties of affected-sib-pair linkage analysis. AB - The likelihood-ratio method for affected-sib-pair analysis, introduced by Risch, is a powerful method for detecting linkage when the marker is not perfectly polymorphic, as is often the case. The power of this method can be improved by restricting maximization to the set of possible haplotype-sharing probabilities- denoted the "possible triangle" method. The asymptotic distributions of the resulting distributions are derived, enabling test criteria to be found for any required test size (i.e., the probability of falsely detecting linkage when none exists) and enabling p values to be assigned to results. The criteria were found to be approximately constant when the PIC of the marker varies, making them applicable to any marker. The asymptotic power approximations were used to investigate the relative performance of pairs with typed parents, relative to those without, by comparing the sample sizes necessary for a given power. Under certain circumstances, typing the parents proved to be inefficient, even when PIC was low. PMID- 8430698 TI - An informative panel of somatic cell hybrids for physical mapping on human chromosome 19q. AB - A panel of 22 somatic cell hybrids divides the q arm of human chromosome 19 into 22 ordered subregions. The panel was characterized with respect to 41 genetic markers. In most cases, a single fragment of chromosome 19 was present in each hybrid. In two cell lines the presence of multiple fragments of the chromosome was demonstrated by segregation of these fragments in subclones. On the basis of the results of marker analysis in this panel, the most likely order of the markers tested is MANB-D19S7-PEPD-D19S9-GPI-C/EBP-TGFB1++ + (CYP2A,BCKDHA,CGM2,NCA)-PSG1-(D19S8, XRCC1)-(ATP1A3,D19S19)-(D19S37,APOC2)-C KM ERCC2-ERCC1-(D19S116,D19S117)- (D19S118,D19S119, D19S63,p36.1,D19S112,D19S62,D19S51,D19S54, D19S55)-pW39-D19S6-(D19S50,TNNT1) D19S2 2-(HRC,CGB,FTL,PRKCG)-qter. This gene order is generally consistent with published physical and genetic mapping orders, although some discrepancies exist. By means of a mapping function that relates the frequency of cosegregation of markers to the distance between them, estimates were made of the sizes, in megabases, of the 19q subregions. The relative physical distances between reference markers were compared with published genetic distances for 19q. Excellent correlation was observed, suggesting that the physical distances calculated by this method are predictive of genetic distances in this region of the genome and, therefore, are just as useful in estimating relative positions of markers. PMID- 8430699 TI - A single major-gene defect underlying cardiac conotruncal malformations interferes with myocardial growth during embryonic development: studies in the CTD line of keeshond dogs. AB - The common forms of isolated congenital heart disease are usually not inherited in a Mendelian pattern, and most are considered multifactorial threshold traits. A large subset consisting of a group of malformations of the ventricular outflow region, termed "conotruncal defects" (CTDs), include subarterial ventricular septal defects, tetralogy of Fallot, and persistent truncus arteriosus. Similar aggregations of CTDs have been reported in human families and in the keeshond breed of dog. The results of our early breeding experiments utilizing noninbred keeshonds were not consistent with any hypothesis of a fully penetrant monogenic inheritance. Here we report a recent series of genetic and embryologic studies conducted after more than 10 generations of selective inbred matings between affected-CTD-line dogs. The results are now consistent with a defect at a single autosomal locus, the Mendelian pattern of transmission having been obscured prior to selective inbreeding by genetic background. On the basis of morphometric embryologic studies, the mutant CTD allele causes conotruncal malformations in homozygous animals by interfering with myocardial growth in the conotruncus during the critical window when the conotruncal cushions fuse to form the conotruncal septum. PMID- 8430700 TI - Refined genetic localization for central core disease. AB - Central core disease (CCO) is an autosomal dominant myopathy clinically distinct from malignant hyperthermia (MHS). In a large kindred in which the gene for CCO is segregating, two-point linkage analysis gave a maximum lod score, between the central core disease locus (CCO) and the ryanodine receptor locus (RYR1), of 11.8, with no recombination. Mutation within RYR1 is responsible for MHS, and RYR1 is also a candidate locus for CCO. A combination of physical mapping using a radiation-induced human-hamster hybrid panel and of multipoint linkage analysis using the Centre d'Etude du Polymorphisme Humain families established the marker order and sex-average map distances (in centimorgans) on the background map as D19S75-(5.2)-D19S9-(3.4)-D19S191-(2.2)-RYR1-(1.7)-D19S190-(1.6)-D19S47-(2.0)- CYP2B. Recombination was observed between CCO and the markers flanking RYR1. These linkage data are consistent with the hypothesis that CCO and RYR1 are allelic. The most likely position for CCO is near RYR1, with a multipoint lod score of 11.4, in 19q13.1 between D19S191 and D19S190, within the same interval as MHS (RYR1). PMID- 8430701 TI - Molecular analyses of a tyrosinase-negative albino family. AB - Sequence analysis of the tyrosinase coding region from an individual with tyrosinase-negative oculocutaneous albinism revealed that the patient was a compound heterozygote. One allele carried a C--> A single-base substitution in codon 355 of exon 3, and the other carried a two-nucleotide deletion in exon 1. The nucleotide substitution caused a putative amino acid change from threonine (ACA) to lysine (AAA), abolishing a signal for N-glycosylation. The two base-pair deletion caused a frameshift, creating a putative premature termination signal at codon 226. The melanocytes from the proband and her affected brother were amelanotic and devoid of measurable tyrosinase activity. Moreover, gel electrophoretic analysis of the immunoprecipitated proband tyrosinase showed that the protein was not processed to the mature glycosylated form, confirming the predicted consequence of the amino acid change. The two-base deletion on the homologous allele was detected only by sequencing genomic DNA. The transcript of this allele was not represented in the cDNA library and could not be detected by PCR mRNA, and the putative truncated protein (approximately 25 kDa) was not present in immunoprecipitates, suggesting that the allele with the missense mutation may be preferentially expressed. PMID- 8430703 TI - The postulated X-inactivation center at Xq27 is most reasonably explained by ascertainment bias: heterozygous expression of recessive mutations is a powerful means of detecting unbalanced X inactivation. PMID- 8430704 TI - Forensic population genetics and the National Research Council (NRC) PMID- 8430702 TI - Occurrence of a 2-bp (AT) deletion allele and a nonsense (G-to-T) mutant allele at the E2 (DBT) locus of six patients with maple syrup urine disease: multiple exon skipping as a secondary effect of the mutations. AB - We have identified two novel mutant alleles in the transacylase (E2) gene of the human branched-chain alpha-keto acid dehydrogenase (BCKAD) complex in 6 of 38 patients with maple syrup urine disease (MSUD). One mutation, a 2-bp (AT) deletion in exon 2 of the E2 gene, causes a frameshift downstream of residue ( 26) in the mitochondrial targeting presequence. The second mutation, a G-to-T transversion in exon 6 of the E2 gene, produces a premature stop codon at Glu-163 (E163*). Transfection of constructs harboring the E163* mutation into an E2 deficient MSUD cell line produced a truncated E2 subunit. However, this mutant E2 chain is unable to assemble into a 24-mer cubic structure and is degraded in the cell. The 2-bp (AT) deletion and the E163* mutant alleles occur in either the homozygous or compound-heterozygous state in the 6 of 38 unrelated MSUD patients studied. Moreover, an array of precise single- and multiple-exon deletions were observed in many amplified E2 mutant cDNAs. The latter results appear to represent secondary effects on RNA processing that are associated with the MSUD mutations at the E2 locus. PMID- 8430705 TI - The transmission probability model is useful to prevent false inference. PMID- 8430706 TI - An exclusion map covering the whole genome: a new challenge for genetic epidemiologists? PMID- 8430707 TI - Are transfusions overrated? Surgical outcome of Jehovah's Witnesses. AB - Physicians as well as their patients are quite familiar with the ever growing list of complications of transfusion. Blood is usually administered by physicians with the nearly unchallenged view that failure to transfuse would have dire consequences. Evidence supporting that view is very difficult to obtain. Although no controlled trial exists, data are collected from 16 reports of the surgical outcome of a series of patients of the Jehovah's Witness faith who were not given transfusion for operations during which transfusion is typically given. Analysis of these data supports the concept that approximately 0.5% to 1.5% of such operations are complicated by anemia resulting in death. This risk of not transfusing patients must be weighed against the cost, morbidity, and mortality that would be expected to accrue had these patients been transfused. These concepts should be employed whenever one is formulating a risk-benefit ratio for patients for whom transfusion is contemplated. PMID- 8430708 TI - Iron-deficiency anemia: a medically treatable chronic anemia as a model for transfusion overuse. AB - PURPOSE: Transfusion practice in patients with iron deficiency was reviewed. PATIENTS AND METHODS: During the study period, records of 265 consecutive patients with an unsaturated iron-binding capacity of greater than 53.7 mumol/L were evaluated for possible iron-deficiency anemia. RESULTS: Two hundred sixty three patients met the study criteria for iron deficiency. Of these patients, 50 received 1 or more units of red blood cells (RBCs). The transfusion therapy of 12 patients could not be justified; physicians used laboratory results rather than the clinical status of the patients to initiate transfusion therapy. As a result, units of RBCs were transfused to raise the hematocrit to an arbitrarily chosen level. Furthermore, iron therapy was not prescribed for 97 of the 263 iron deficient patients, including 11 of the patients for whom transfusion was justifiable and 2 patients for whom transfusion could not be justified. Based on records reviewed, no work-up was initiated to identify the cause of iron deficiency in 13 patients, including 4 patients who received transfusions. CONCLUSION: These findings suggest that the evaluation and treatment of iron deficiency, including transfusion therapy for that condition, may be problematic. In view of the risks of blood transfusion therapy, improvement in transfusion practices for iron deficiency should be emphasized. PMID- 8430710 TI - Underutilization of pneumococcal vaccine in nursing home in Washington State: report of a serotype-specific outbreak and a survey. AB - PURPOSE: To describe an outbreak of pneumococcal disease in a Washington state nursing home and to report a survey of pneumococcal vaccine utilization in Washington nursing homes. PATIENTS AND METHODS: Outbreak. Data were collected from nursing home residents' records. Nasopharyngeal cultures were obtained from residents and staff. Survey. Fifty-four randomly selected Washington nursing homes were surveyed about pneumococcal vaccine utilization and policies. RESULTS: Outbreak. Three confirmed and 4 possible cases of pneumococcal disease occurred over 9 days among 94 residents; 5 patients (71%) died. Cases were identified among 6 of 42 residents on 1 wing, compared with 1 of 52 on the other 2 wings (relative risk 7.4, 95% confidence interval 1.0, 398.5). Streptococcus pneumoniae serotype 9V was cultured from the blood of 3 confirmed case-patients and the nasopharynx of 2 of 73 residents. Only 7% of residents had received pneumococcal vaccine, including one case-patient who had received 14-valent vaccine without serotype 9V. Survey. Only 22% of residents were reported to have received pneumococcal vaccine; vaccination status was unknown for 66%. Physician discretion determined pneumococcal vaccination in 49 (91%) nursing homes; 9 (17%) had a written policy. Two major barriers to pneumococcal vaccination were cited: low priority among physicians (43%) and difficulty in determining residents' vaccine history (37%). CONCLUSIONS: A pneumococcal disease outbreak among undervaccinated nursing home residents probably resulted from person-to-person transmission. Pneumococcal vaccine appears to be underutilized in Washington state nursing homes. PMID- 8430709 TI - Acute tumor lysis syndrome in patients with high-grade non-Hodgkin's lymphoma. AB - PURPOSE: To identify patients with lymphoma at risk for tumor lysis after chemotherapy. PATIENTS AND METHODS: The case records of 102 patients receiving combination chemotherapy for non-Hodgkin's lymphoma (intermediate to high-grade histology) were reviewed. Patients were considered to have "laboratory tumor lysis" if two of the following metabolic changes occurred within 4 days of treatment: a 25% increase in the serum phosphate, potassium, uric acid, or urea nitrogen concentrations, or a 25% decline in the serum calcium concentration. "Clinical tumor lysis" was defined as laboratory tumor lysis plus one of the following: a serum potassium level greater than 6 mmol/L, a creatinine level greater than 221 mumol/L, or a calcium level less than 1.5 mmol/L, the development of a life-threatening arrhythmia, or sudden death. RESULTS: Laboratory tumor lysis occurred in 42% of patients and clinical tumor lysis in 6%. There was no statistical difference in the frequency of either tumor lysis syndrome among lymphoma subgroups. Clinical tumor lysis occurred more frequently in patients with pretreatment renal insufficiency (serum creatinine level greater than 132 mumol/L) than in patients with normal renal function (36% versus 2%; p = 0.01). The development of azotemia correlated with high pretreatment serum lactate dehydrogenase concentrations (p < 0.01; r2 = 0.11). CONCLUSION: Clinically significant tumor lysis is a rare occurrence in patients with lymphoma when they are receiving allopurinol. However, tumor lysis can occur in patients with all types of moderate to high-grade non-Hodgkin's lymphoma. Patients with a high serum lactate dehydrogenase level or renal insufficiency are at increased risk for metabolic complications after chemotherapy and should be closely monitored. PMID- 8430711 TI - Validation of a pneumonia prognostic index using the MedisGroups Comparative Hospital Database. AB - PURPOSE: Our purpose was to validate a previously developed pneumonia-specific prognostic index in a large, multicenter population. PATIENTS AND METHODS: We developed a pneumonia-specific prognostic index in a prospective, multicenter study of 346 patients with clinical and radiographic evidence of pneumonia admitted to 3 Pittsburgh hospitals (the derivation cohort), and validated the index in 14,199 patients with a principal ICD-9-CM diagnosis of pneumonia admitted to 78 hospitals in the 1989 MedisGroups Comparative Hospital Database (the validation cohort). The prognostic index classified patients into five ordered risk classes based on six predictors of mortality: age greater than 65 years, pleuritic chest pain, a vital sign abnormality, altered mental status, neoplastic disease, and high-risk pneumonia etiology. Each patient in the validation cohort was assigned to a risk class by obtaining values for the index's six predictors in the MedisGroups population. The performance of the prognostic index in the derivation and validation cohorts was assessed by comparing hospital mortality rates within each of the index's five prognostic risk classes. RESULTS: The hospital mortality rate was 13.0% in the derivation cohort, and 11.1% in the validation cohort (p = 0.26). The agreement in the risk class-specific mortality rates was striking with the exception of class V: in class I, mortality was 0% in the derivation cohort versus 1% in the validation cohort; in class II, 0% versus 1.1%; class III, 10.9% versus 8.6%; class IV, 21.8% versus 26.2%; and class V, 73.7% versus 37.7%. There were no statistically significant differences in mortality rates within the first four risk classes, which represented the vast majority of patients in the derivation (94%) as well as the validation (98%) cohorts. CONCLUSIONS: These data support the generalizability of a pneumonia-specific prognostic index. This index, which performs exceptionally well in classifying low-risk patients, may help physicians identify patients with community-acquired pneumonia who could safely be managed in the ambulatory setting, or if hospitalized, the patients that could be treated with abbreviated inpatient care. PMID- 8430712 TI - Hyponatremia in hospitalized patients with the acquired immunodeficiency syndrome (AIDS) and the AIDS-related complex. AB - STUDY OBJECTIVE: To determine the frequency, etiology, and clinical association of hyponatremia in patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC). PATIENTS AND METHODS: A prospective analysis of 167 patients with AIDS and 45 patients with ARC admitted on 259 occasions to a large metropolitan teaching hospital during a 3-month period. RESULTS: Eighty three patients (39%) with hyponatremia (serum sodium concentration less than 135 mmol/L) were observed during 99 hospitalizations, for a frequency of 38%. The mean (+/- standard error) of the lowest serum sodium concentration was 128 +/- 1 mmol/L in the hyponatremic patients and 138 +/- 1 mmol/L in the normonatremic patients. Hyponatremia was present on admission during 57 hospitalizations and was associated with gastrointestinal losses and hypovolemia in 43%. When hyponatremia developed during hospitalization, 68% of the patients were clinically euvolemic and had a syndrome consistent with inappropriate secretion of antidiuretic hormone (SIADH). Patients with hyponatremia were hospitalized longer than those with normal serum sodium concentrations (17 +/- 1 versus 9 +/- 1 days, p < 0.001). In addition, the mortality rate in the hyponatremic group was higher than that in the normonatremic group (36.5% versus 19.7%, p < 0.01). CONCLUSION: Hyponatremia is a common electrolyte disorder in patients hospitalized with AIDS or ARC and is frequently associated with gastrointestinal losses or SIADH as well as increased morbidity and mortality. PMID- 8430713 TI - Application of ambulatory blood pressure monitoring in differentiating between antihypertensive agents. AB - PURPOSE: This multicenter, double-blind, parallel group study assessed the usefulness of the ambulatory blood pressure monitoring (ABPM) technique in differentiating between the once-daily administration of the beta blockers bisoprolol (10 to 20 mg) and atenolol (50 to 100 mg) in terms of efficacy and duration of action. PATIENTS AND METHODS: The study population consisted of 659 patients with essential hypertension and an average office diastolic blood pressure (BP) between 95 and 115 mm Hg after 4 weeks of placebo treatment. Office BPs were recorded at the end of the 24-hour dosing interval (trough). ABPM was performed in 11 of the 28 institutions participating in this study in a total of 203 patients. These procedures were performed at the end of the placebo phase and again after 8 weeks of active treatment. RESULTS: With the use of conventionally measured office BPs, the two drugs significantly (p < 0.001) decreased trough systolic and diastolic BPs to a similar extent. By 24-hour monitoring, bisoprolol demonstrated a 33% greater reduction in whole-day average diastolic BP than did atenolol (11.6 +/- 0.7 mm Hg versus 8.7 +/- 0.8 mm Hg, p < 0.01). Significant treatment differences in systolic (p < 0.05) and diastolic (p < 0.01) BPs were also noted for bisoprolol compared with atenolol during the final 4 hours of the dosing interval (-13.2 +/- 1.5/-10.9 +/- 1.0 mm Hg versus -8.9 +/- 1.6/-7.3 +/- 1.1 mm Hg, respectively), and over the time period 6:00 AM to noon (-14.2 +/- 1.3/-11.5 +/- 0.9 mm Hg versus -9.9 +/- 1.4/-7.7 +/- 0.9 mm Hg). CONCLUSIONS: Whereas conventional BP measurements did not detect differences in the antihypertensive effects of the beta blockers bisoprolol and atenolol, ABPM revealed significant treatment differences in both the efficacy and duration of action of these two agents. These findings indicate the power of this technique to discriminate potentially important differences between apparently similar antihypertensive drugs. PMID- 8430714 TI - Can moderate chronic obstructive pulmonary disease be diagnosed by historical and physical findings alone? AB - BACKGROUND: The value of the history and physical examination in diagnosing chronic obstructive pulmonary disease (COPD) is uncertain. This study was undertaken to determine the best clinical predictors of COPD and to define the incremental changes in the ability to diagnose COPD that occur when the physical examination findings and then the peak flowmeter results are added to the pulmonary history. SUBJECTS AND METHODS: Ninety-two outpatients with a self reported history of cigarette smoking or COPD completed a pulmonary history questionnaire and received peak flow and spirometric testing. The subjects were independently examined for 12 physical signs by 4 internists blinded to all other results. Multivariate analyses identified independent predictors of clinically significant, moderate COPD, defined as a forced expiratory volume in 1 second (FEV1) less than 60% of the predicted value or a FEV1/FVC (forced vital capacity) less than 60%. RESULTS: Fifteen subjects (16%) had moderate COPD. Two historical variables from the questionnaire--previous diagnosis of COPD and smoking (70 or more pack-years)--significantly entered a logistic regression model that diagnosed COPD with a sensitivity of 40% and a specificity of 100%. Only the physical sign of diminished breath sounds significantly added to the historical model to yield a mean sensitivity of 67% and a mean specificity of 98%. The peak flow result (best cutoff value was less than 200 L/min) significantly added to the models of only one of the four physicians for a mean final sensitivity of 77% and a specificity of 95%. Subjects with none of the three historical and physical variables had a 3% prevalence of COPD; this prevalence was unchanged by adding the peak flow results. CONCLUSIONS: Diminished breath sounds were the best predictor of moderate COPD. A sequential increase in sensitivity and a minimal decrease in specificity occurred when the quality of breath sounds was added first to the medical history, followed by the peak flow result. The chance of COPD was very unlikely with a normal history and physical examination. PMID- 8430715 TI - Immunologic and psychologic therapy for patients with chronic fatigue syndrome: a double-blind, placebo-controlled trial. AB - PURPOSE: To evaluate the potential benefit of immunologic therapy with dialyzable leukocyte extract and psychologic treatment in the form of cognitive-behavioral therapy (CBT) in patients with chronic fatigue syndrome (CFS). PATIENTS AND METHODS: Immunologic and psychologic treatments were administered to 90 adult patients who fulfilled diagnostic criteria for CFS in a double-blind, randomized, and placebo-controlled study. A four-cell trial design allowed the assessment of benefit from immunologic and psychologic treatment individually or in combination. Outcome was evaluated by measurement of global well-being (visual analogue scales), physical capacity (standardized diaries of daily activities), functional status (Karnofsky performance scale), and psychologic morbidity (Profile of Mood States questionnaire), and cell-mediated immunity was evaluated by peripheral blood T-cell subset analysis and delayed-type hypersensitivity skin testing. RESULTS: Neither dialyzable leukocyte extract nor CBT (alone or in combination) provided greater benefit than the nonspecific treatment regimens. CONCLUSIONS: In this study, patients with CFS did not demonstrate a specific response to immunologic and/or psychologic therapy. The improvement recorded in the group as a whole may reflect both nonspecific treatment effects and a propensity to remission in the natural history of this disorder. PMID- 8430716 TI - Ergolytic drugs in medicine and sports. AB - Just as drugs that enhance exercise capacity and/or athletic performance are often called "ergogenic," drugs that impair these functions can be termed "ergolytic." Today's athletes hear too much about the former and too little about the latter. Ergolytic drugs used today by certain athletes include alcohol, marijuana, smokeless tobacco, cocaine, antihypertensives, eye drops, and diuretics. Some antidepressants, too, can be ergolytic, as well as some antihistamines and other common drugs--even caffeine--in some settings, for some people. Internists can help their fitness-minded patients by educating them about ergolytic drugs and by tailoring their management to foster peak performance at work and play. PMID- 8430717 TI - Acyclovir-induced neurotoxicity: concentration-side effect relationship in acyclovir overdose. AB - PURPOSE: To investigate the concentration-side effect relationship in a patient with severe acyclovir-induced neurotoxicity and to summarize the information available in the literature about central nervous system side effects due to acyclovir. METHODS: Repeated blood samples were drawn in a patient with severe acyclovir overdose who developed coma and nonoliguric renal failure. The acyclovir levels measured by radioimmunoassay were related to the level of consciousness. RESULTS: We measured the highest acyclovir serum levels reported so far (229.9 mumol/L = 51.8 mg/L). Impairment of consciousness developed with a remarkable temporal delay of 24 to 48 hours after occurrence of peak serum concentrations and resolved with a comparable delay after reaching the therapeutic range (anticlockwise hysteresis). Six days after discontinuation of the drug, central nervous system symptoms had resolved, and, 4 days later, renal function returned to pretreatment values. CONCLUSIONS: The observation that neurotoxicity developed with a delay of 24 to 48 hours after acyclovir peak serum concentrations could explain the wide range of acyclovir levels reported in similar cases. Single drug level measurements may therefore be of little diagnostic value. Since toxicity develops with a remarkable delay, early removal of the drug (by hemodialysis) could possibly prevent central nervous toxicity. PMID- 8430718 TI - Duodenal obstruction by abdominal aortic aneurysm. PMID- 8430719 TI - Myelinolysis is due to rapid correction of hyponatremia. PMID- 8430720 TI - Erythromycin ototoxicity: methodology and conclusions. PMID- 8430721 TI - The Cruzan decision. PMID- 8430722 TI - Retinal detachment as a potential hazard in surgical correction of severe myopia with phakic anterior chamber lenses. AB - Phakic anterior chamber lenses have been proposed as an effective refractive surgical procedure for the correction of severe myopias. We managed three cases of retinal detachment that complicated this operation. Two patients had retinal detachment in the immediate postoperative period at the fourth and sixth weeks, respectively. Both patients had preoperative equatorial lattice degeneration, which was prophylactically managed with argon laser in one case. The third patient developed retinal detachment at the eighth postoperative month and was associated with a severe fibrinoid uveitis and a combined exudative and rhegmatogenous retinal detachment. This third patient did not have any previous retinal degenerative lesion. Scleral buckling was successful in two of the patients, whereas the patient with preoperative inflammation required vitreous surgery because of proliferative vitreoretinopathy. The retinas were reattached in all three patients without explanting the phakic anterior chamber lens, but severe loss of visual acuity occurred in one patient. Retinal detachment should be regarded as a potentially important hazard in this type of refractive surgery. PMID- 8430723 TI - Birdshot chorioretinopathy and Lyme borreliosis. AB - Two patients in whom ocular Lyme disease was suspected and who had antibodies to Borrelia burgdorferi developed birdshot chorioretinopathy and carried the HLA-A29 antigen. In a series of 11 patients with birdshot chorioretinopathy who carried the HLA-A29 antigen, three patients had antibodies against B. burgdorferi as determined by either immunofluorescence assay, enzyme-linked immunosorbent assay, Western blot analysis, or a combination of these tests. Further studies will be necessary to evaluate whether this is a false-positive reaction or whether B. burgdorferi has a causative role in the pathogenesis of birdshot chorioretinopathy. PMID- 8430724 TI - Fundus changes associated with congenital hypertrophy of the retinal pigment epithelium. AB - The clinical characteristics and follow-up changes of 64 patients with solitary congenital hypertrophy of the retinal pigment epithelium were studied. Thirty five of the patients were followed up for one to 14 years with serial fundus photography. Progressive increase of the hypopigmented part of the lesion was observed in 29 of the 35 patients who were followed up (82.8%). An enlargement of the lesion was seen in 26 of the 35 patients (74.3%). Two additional changes, that is, pigmented areas adjacent to congenital hypertrophy of the retinal pigment epithelium and linear streaks of the pigment epithelium, were documented. Pathogenetic mechanisms for the development of these changes remain unknown. PMID- 8430725 TI - Hyperhomocysteinemia in retinal artery and retinal vein occlusion. AB - In 19 patients who had retinal vein occlusion or retinal artery occlusion before the age of 50 years, the incidence of hyperhomocysteinemia, as observed in heterozygosity for homocystinuria, was studied by the performance of a standardized, oral methionine-loading test. In four of the 19 patients (21%), two with retinal artery occlusion and two with central retinal vein occlusion, the after-load peak levels of homocysteine exceeded the mean level, established in normal control subjects, by more than two standard deviations and were as well within the ranges established in obligate heterozygotes for homocystinuria. Because the frequency of heterozygosity for homocystinuria in the normal population is one in 70 (1.4%) at the most, we conclude that hyperhomocysteinemia predisposes to the development of premature retinal artery and retinal vein occlusion (P < .01; chi 2 test). PMID- 8430726 TI - Velocity of ophthalmic arterial flow recorded by Doppler ultrasound in normal subjects. AB - Transcranial Doppler ultrasound (2 MHz) was used to measure ophthalmic arterial blood flow velocity in 60 normal subjects whose mean age (+/- standard deviation) was 54.9 +/- 17.3 years (30 women, mean age, 56.3 +/- 17.5 years and 30 men, mean age, 53.5 +/- 17.3 years). Three or more measurements were recorded from each eye at reference depths of 40 to 45 mm. The peak systolic flow velocity was 45.1 +/- 7.8 cm/sec, mean-enveloped flow velocity was 22.6 +/- 5.1 cm/sec, end diastolic flow velocity was 12.0 +/- 3.4 cm/sec, pulsatility index was 1.5 +/- 0.4, and resistivity index was 0.7 +/- 0.1. No significant differences of flow variables were found between genders. Statistically significant age-related losses of mean enveloped flow velocity and end diastolic flow velocity were shown (P = .003 and .038). There were no significant differences of flow velocities between right and left eyes when comparing means. Differences greater than 20% between eyes were found in ten subjects (16.7%) for peak systolic flow velocity, in 18 subjects (30.4%) for mean-enveloped flow velocity, and in 21 subjects (34.8%) for end diastolic flow velocity, but resistivity indexes were comparable in all cases. Ten subjects had flow velocities measured at two different depths separated by 10 mm (40 to 45 mm vs 50 to 55 mm) in the same orbit and showed that peak systolic flow velocity and mean-enveloped flow velocity were significantly higher (P = .006 and .021) at the greater depth. Recognizable differences in shape of the spectrograms obtained from the younger subjects (< or = 30 years) and the older subjects (> or = 70 years) were found. PMID- 8430727 TI - Regression of retinoblastoma after plaque radiotherapy. AB - A review of 400 consecutive patients with retinoblastoma disclosed that 103 tumors in 103 eyes were treated with solitary plaque radiotherapy. The tumors were from 1 to 16 mm (mean, 7 mm) in basal diameter and from 1 to 8 mm (mean, 4 mm) in thickness. Thirty-one tumors were treated with plaque radiotherapy as initial treatment, whereas 72 tumors were treated with plaque radiotherapy as secondary treatment after failure of other methods. Of the 102 tumors on which adequate follow-up data were available, all responded initially to plaque radiotherapy with tumor regression. Over the mean follow-up of 38 months (range, six to 192 months), 89 tumors (87%) showed persistent regression and 13 (13%) showed tumor recurrence. The recurrence occurred at a mean interval of five months (range, one to 11 months) after plaque radiotherapy. A statistical analysis of tumor size, tumor location, tumor proximity to the optic disk and foveola, presence of vitreous seeds, radioactive plaque diameter, plaque shape, radioisotope, and primary or secondary treatment disclosed no important predictors of tumor recurrence. Carefully selected retinoblastoma, even juxtapapillary and macular tumors and those with localized vitreous seeds, can be successfully treated with plaque radiotherapy. PMID- 8430728 TI - A comparison of corneal endothelial changes after use of Healon or Viscoat during phacoemulsification. AB - We conducted a prospective, randomized trial comparing the endothelial protective effects of Healon (Kabi Pharmacia Ophthalmics, Inc., Monrovia, California) and Viscoat (Alcon Surgical, Inc., Ft. Worth, Texas) in 59 eyes of 59 patients undergoing iris-plane or posterior-chamber phacoemulsification with posterior chamber lens implantation. We evaluated postoperative central and superior changes in corneal thickness and corneal endothelial cell density, coefficient of variation in cell size, and percentage of hexagons. In the overall series, at one day postoperatively, corneal thickness increased 17% centrally and superiorly in eyes receiving Healon compared to 12% centrally and 11% superiorly in eyes receiving Viscoat (P < .05). Sixteen weeks postoperatively, superior endothelial cell loss was 11.6% in eyes receiving Healon compared to 2.1% in eyes receiving Viscoat (P < .01). In the iris-plane phacoemulsification group, superior cell loss at week 16 was 13.8% in eyes receiving Healon and 0.5% in eyes receiving Viscoat (P < .04). In the posterior-chamber phacoemulsification group, there were no significant differences between the Healon and Viscoat subgroups. Comparing the surgical techniques, in the Healon group, central cell loss at week 16 was 13.8% in the iris-plane phacoemulsification subgroup and 0.6% in the posterior chamber phacoemulsification subgroup (P < .03), and coefficient of variation in cell size increased 3.7% in the iris-plane subgroup and decreased 6.8% in the posterior-chamber subgroup (P < .04). In the Viscoat group, there were no significant differences between surgical techniques at week 16. Viscoat provided greater corneal endothelial protection than Healon during iris-plane phacoemulsification. In eyes receiving Healon, posterior-chamber phacoemulsification resulted in less corneal endothelial trauma than the iris plane technique. PMID- 8430729 TI - Spontaneous ulcerative keratitis in immunocompromised patients. AB - We studied the occurrence of ulcerative keratitis in five eyes of four patients who were examined at the University of Maryland Hospital ophthalmology clinic over a 12-month period. All were young women who were intravenous drug abusers, with no known predisposing factors for ulcerative keratitis. Two patients had acquired immunodeficiency syndrome (AIDS), one was human immunodeficiency virus (HIV)-positive, and the fourth refused HIV testing. One had a corneoscleral limbus to corneoscleral limbus keratitis; three had inferiorly located corneal ulcers (bilateral in one patient with AIDS). Corneal cultures disclosed Capnocytophaga species in the corneoscleral limbus to corneoscleral limbus keratitis. The remaining ulcers were polymicrobial; cultures of three grew Candida albicans, cultures of two grew alpha-hemolytic streptococci, cultures of two grew Staphylococcus aureus, and culture of one grew Pseudomonas aeruginosa. Treatment with topical fortified antibiotics and antifungal agents resulted in complete healing in all four inferiorly located ulcers. The corneal ulcer became perforated and the eye was eviscerated. Histopathologic analysis of the eviscerated specimen disclosed acute keratitis with necrosis and no microorganisms. PMID- 8430730 TI - Computerized topographic analysis of the healing graft after penetrating keratoplasty for keratoconus. AB - After penetrating keratoplasty, visual rehabilitation can be slow and is largely a function of corneal surface configuration. Computerized topographic analysis allows the detailed study of corneal surface factors that determine the optical function of the graft. We performed a prospective, longitudinal study of eight patients with keratoconus by using computerized topographic analysis to determine the rate and pattern of postoperative surface normalization and stabilization. Study data included Snellen visual acuity, contrast sensitivity function, central keratometry, photokeratoscopy, and computerized topographic analysis. Data were collected preoperatively and at one week, one month, two months, three months, and six months postoperatively. Results demonstrate that the greatest configurational changes both topographically and functionally occur in the first month after keratoplasty. The computer-generated surface asymmetry index and the surface regularity index correlated well with improvement in Snellen visual acuity measurements. Contrast sensitivity function was depressed initially but improved to well above preoperative values by one month postoperatively and paralleled the improvement in the surface indices and visual acuity. The axis of astigmatism stabilized by one month postoperatively. Our data indicate that topographic analysis provides a good indication of the rate and course of optical stabilization during the early healing process after keratoplasty and correlates well with visual function in the otherwise normal eye. PMID- 8430731 TI - Dermatochalasis and dry eye. AB - The medical records of 141 patients with dermatochalasis seen during the 32-month period of January 1989 through August 1991 were reviewed. Patients were classified on the basis of symptoms and mode of treatment and were examined for effectiveness of blepharoplasty in ameliorating these symptoms. Seventy-three patients (51.8%) had symptoms similar to those found in keratoconjunctivitis sicca, including mattering, burning, itching, redness, epiphora, foreign-body sensation, and photophobia. Of these 73 patients, 38 (52.1%) underwent upper eyelid blepharoplasty. Subjective improvement in symptoms was achieved in 33 of these patients (86.8%) postoperatively. Upper eyelid blepharoplasty may represent an effective component in the treatment of patients with dermatochalasis and dry eye symptoms. PMID- 8430732 TI - Picosecond neodymium:yttrium lithium fluoride laser sclerectomy. AB - The picosecond neodymium:yttrium lithium fluoride laser, a high-power, short pulse laser that uses low energy per pulse and has a high repetition rate and a highly coherent energy source of 1,053 nm, was used to perform sclerectomies by an ab externo approach in human cadaver eyes. We evaluated laser settings with regard to full-thickness scleral perforation and thermal damage to surrounding tissue. We studied energy per pulse, depth per burst (a present number of spots), spot and line separation of the pattern (spacing between spots of the laser in length [spot separation] and width [line separation]), and total energy required to perforate the sclera. Efficiency was determined by evaluating which settings required the fewest spots and least total energy to perforate the sclera. We studied histologic sections of the sclerectomy sites to determine thermal damage to the surrounding sclera. The picosecond neodymium:yttrium lithium fluoride laser is effective in performing full-thickness sclerectomy with minimal thermal damage to the surrounding tissue. The anterior chamber could be penetrated with an average total energy of 13.3 +/- 0.4 (SEM) J. The sclerectomy size was 545 +/- 11 microns externally and 163 +/- 4 microns internally. Successful sclerectomies were performed with as little as 3 to 5 microns of thermal damage to the surrounding scleral tissue with 250 microJ per pulse. PMID- 8430733 TI - Short-wavelength color visual fields in glaucoma suspects at risk. AB - Glaucoma suspect eyes were seen during a five-year study on color visual fields that used a 440-nm test on a bright-yellow background (96 normal eyes, 55 suspect eyes, and 110 eyes that developed glaucoma). The predictive ability of the test was assessed in 25 eyes followed up for more than one year, five of which developed glaucoma. These five eyes and those at high risk showed higher mean defect (P < .0001) and number of defective points (P < .0001) than the other suspect groups, which were not significantly different from normal eyes. The mean defects (+/- standard deviations) and average number of defective points were 1.4 +/- 2.3 dB with 8.9 points (low-risk eyes), 1.1 +/- 1.2 dB with 8.0 points (medium-risk eyes), 6.7 +/- 2.8 dB with 27.7 points (high-risk eyes), and 9.3 +/- 1.8 dB with 39.4 points (eyes that developed glaucoma). Normal eyes had an average of 3.4 defective points. These results were similar when all 55 suspect eyes were analyzed. Color visual fields identify early functional loss in eyes at greatest risk for primary open-angle glaucoma. PMID- 8430734 TI - Transient posterior subcapsular lens opacities in diabetes mellitus. AB - In three patients with transient cataracts the lenticular opacities were feathery in nature, and posterior subcapsular in location. They appeared to emanate from a dense central posterior subcapsular plaque. These opacities were examined with the slit lamp and documented photographically. The onset of cataract was abrupt in all three patients, and resolved over a three- to 36-day period. Two patients had bilateral reversible cataracts, and in one of these patients the lenticular opacities were recurrent. Two of the patients had been taking oral corticosteroids. Temporary cataracts have been previously reported in patients with poor diabetic control. Diabetes mellitus had been diagnosed in only one of our patients. Three-hour glucose tolerance testing of the other two patients disclosed mildly increased one-hour blood glucose levels. We believe that reversible lens opacities may occur in subclinical diabetes mellitus with normal or only mildly increased blood glucose levels. PMID- 8430735 TI - Rhabdomyosarcoma manifesting as acquired nasolacrimal duct obstruction. AB - A 5-month-old boy with acquired epiphora developed a right inferonasal lower eyelid mass, which was shown on computed tomography to involve the inferior and medial recti muscles and the nasolacrimal duct. Orbital exploration and excision of the mass disclosed this to be an embryonal rhabdomyosarcoma. This case illustrates the importance of distinguishing acquired nasolacrimal duct obstruction in infancy from true congenital nasolacrimal duct obstruction. PMID- 8430736 TI - Ocular manifestations of the lacrimo-auriculo-dento-digital syndrome. AB - We studied a mother and daughter with an extremely rare constellation of signs and symptoms. One or both had absent lacrimal puncta, nasolacrimal duct obstruction, chronic dacryocystitis, dry eyes, and epiphora. Systemic findings included salivary gland hyposecretion, dental hypoplasia and dysplasia, cup shaped ears with hearing loss, and digital anomalies. These findings are consistent with those of the lacrimo-auriculo-dento-digital syndrome, a genetic disorder. Our study supports the autosomal dominant inheritance of this syndrome, delineates the ophthalmic manifestations, and provides evidence that renal anomalies are part of the disorder. PMID- 8430737 TI - The correction of myopia with phakic intraocular lenses. PMID- 8430738 TI - Polymicrobial keratitis resulting from a dental pick injury. PMID- 8430740 TI - Alcaligenes faecalis corneal ulcer in a patient with cicatricial pemphigoid. PMID- 8430739 TI - Infectious scleritis after a diabetic foot ulcer. PMID- 8430741 TI - Glutaraldehyde keratopathy. PMID- 8430742 TI - Hyperoxia and transient resolution of vascular vasodilation and tortuosity in threshold retinopathy of prematurity. PMID- 8430743 TI - Antibiotic-resistant tuberculous choroiditis. PMID- 8430744 TI - Unilateral optic disk edema and a contralateral temporal fossa mass. PMID- 8430745 TI - Diagnostic misinterpretation of fat suppression orbital magnetic resonance scanning. PMID- 8430746 TI - Management of unsuccessful tarsorrhaphy separation with polytetrafluoroethylene (Gor-Tex) stent. PMID- 8430747 TI - Glove perforations in ophthalmic surgery. PMID- 8430748 TI - Progression of nonproliferative diabetic retinopathy and visual outcome after extracapsular cataract extraction and intraocular lens implantation. PMID- 8430749 TI - Intraocular lens power calculations for multifocal intraocular lenses. PMID- 8430750 TI - Neandertal supralaryngeal vocal tract. AB - Interpretations of skeletal anatomy claiming to show that Neandertals could not have had a similar supralaryngeal vocal apparatus to that of humans are demonstrated to be flawed. Correction of the errors suggests that the Neandertal vocal apparatus need not have differed from that of recent humans. PMID- 8430751 TI - Effects of annular cranial vault modification on the cranial base and face. AB - Artificial modification of the cranial vault was practiced by a number of prehistoric and protohistoric populations, frequently during an infant's first year of life. We test the hypothesis that, in addition to its direct effects on the cranial vault, annular cranial vault modification has a significant indirect effect on cranial base and facial morphology. Two skeletal series from the Pacific Northwest Coast, which include both nonmodified and modified crania, were used: the Kwakiutl (62 nonmodified, 45 modified) and Nootka (28 nonmodified, 20 modified). Three-dimensional coordinates of 53 landmarks were obtained using a diagraph, and 36 landmarks were used to define nine finite elements in the cranial vault, cranial base, and face. Finite element scaling was used to compare average nonmodified and average modified crania, and the significance of the results were evaluated using a bootstrap test. Annular modification of the cranial vault produces significant effects on the morphology of the cranial base and face. Annular modification in the Kwakiutl resulted in restrictions of the cranial vault in the medial-lateral and superior-inferior dimensions and an increase in anterior-posterior growth. Similar dimensional changes are observed in the cranial base. The Kwakiutl face is increased anterior-posteriorly and reduced anterior-laterally to posterior-medially. Similar effects of modification are observed in the Nootka cranial vault and cranial base, though not in the face. These results demonstrate the developmental interdependence of the cranial vault, cranial base, and face. PMID- 8430752 TI - Dermatoglyphic asymmetry and testosterone levels in normal males. AB - Dermatoglyphic prints and salivary samples were taken on a sample of 39 adult males. A statistical relationship between dermatoglyphic asymmetry and adult testosterone levels as measured in saliva was examined for seven dermatoglyphic variables by means of correlation, regression, and analysis of covariance, controlling for age and stature when necessary. The first two types of analyses indicated a significant effect of testosterone level upon the asymmetry of three dermatoglyphic variables: a-b ridge count, palmar pattern intensity, and the combined pattern intensity of palm and digits. Analysis of covariance, which examined the effect of testosterone level as a categorical variable, while holding age or stature constant, demonstrated the asymmetry of five variables to be significantly affected by testosterone level: radial digital count, digital pattern intensity, palmar pattern intensity, total digital ridge count, and the combined palmar and digital intensity. Although there is as yet only associational evidence linking levels of prenatal and secondary testosterone, the results of the present study lend support to the hypothesis that prenatal testosterone levels may have a significant effect on the development of dermatoglyphics. PMID- 8430753 TI - Sex determination of infant and juvenile skeletons: I. Morphognostic features. AB - Ancient cemeteries are often characterized by a considerable number of infants and young children. Sex differences in childhood mortality, however, could rarely be studied up to now, mainly because there were only few proven traits for sexual determination of immature skeletons. Based on a historic sample of sixty-one children of known sex and age from Spitalfields, London (37 boys, 24 girls), sexually distinctive traits in the mandible and ilium are presented for morphognostic diagnosis. Besides other features, boys typically show a more prominent chin, an anteriorly wider dental arcade, and a narrower and deeper sciatic notch than girls. Most of the traits presented in this study allow individuals between birth and five years of age to be successfully allocated to either sex in 70-90% of the cases. PMID- 8430754 TI - Radiographic estimation of long bone cross-sectional geometric properties. AB - Because of their biomechanical significance, cross-sectional geometric properties of long bone diaphyses (areas, second moments of area) have been increasingly used in a number of form/function studies, e.g., to reconstruct body mass or locomotor mode in fossil primates or to elucidate allometric scaling relationships among extant taxa. In the present study, we test whether these biomechanical section properties can be adequately estimated using biplanar radiographs, as compared to calculations of the same properties from computer digitization of cross-sectional images. We are particularly interested in smaller animals, since the limb bone cortices of these animals may not be resolvable using other alternative noninvasive techniques (computed tomography). The test sample includes limb bones of small (25-5,000 g) relatively generalized quadrupedal mammals--mice, six species of squirrels, and Macaca fascicularis. Results indicate that biplanar radiographs are reasonable substitutes for digitized cross-sectional images for deriving areas and second moments of area of midshaft femora and humeri of mammals in this size range. Potential application to a variety of questions relating to mechanical loading patterns in such animals is diverse. PMID- 8430755 TI - Testicle size of orang-utans in relation to body size. AB - Few data are available for assessing the relative testicle size of orang-utans, Pongo pygmaeus, so measures were obtained for 31 individuals of varying age. It was shown that the volume of the testicles, calculated from in situ measures of testicle length and breadth, closely approximates testicle weight when multiplied by the specific gravity of solid tissue. Growth curves for body weight and data published for wild specimens were evaluated to obtain the weight most characteristic of male Pongo, and the ratio of testicle weight to body weight was calculated. The mean ratio for individuals with fully adult stature is 0.034, similar to but smaller than that of humans at about 0.050, and larger than the ratios reported for 5 gorillas at 0.013. The testicles mature faster than the body, however, so the mean ratio for young adult orang-utans is about 0.056 and resembles the ratio for humans more closely than the full adults. The differences between the ratios for a monogamous gibbon species, orang-utans, and humans is accounted for when testicle size relative to the weight of the female is considered. This is consistent with a sperm dilution effect produced by variation in the size of the female reproductive tract. The small relative testicle size of the gorilla is anomalous and requires verification as does the application of female size to scale the testicles. PMID- 8430756 TI - Hominoid heterochromatin: terminal C-bands as a complex genetic trait linking chimpanzee and gorilla. AB - The genetic relations of the apes have been the source of contention throughout the last decade. A potentially useful suite of phylogenetic characters is the distribution of darkly staining material (heterochromatin) in the chromosomes of the apes. While the precise etiology of this character suite remains unclear, it appears to be fairly easily reconciled to hominoid phylogeny in general. The distribution of heterochromatin at the tips of the chromosomes of gorillas and chimpanzees suggests a phylogenetic association between those two taxa exclusive of humans. PMID- 8430757 TI - Premaxilla in African apes: comment on Mooney and Siegel (1991). PMID- 8430758 TI - In memoriam: Alun R. Hughes (1916-1992). PMID- 8430759 TI - Uterine contraction and physiological mechanisms of modulation. AB - Control of the smooth muscle in the uterus (the myometrium), is of vital importance during pregnancy and parturition. It is therefore understandable that several physiological mechanisms (neuronal, hormonal, metabolic, and mechanical) play a role in the control of myometrial activity. As our knowledge of the mechanism of uterine contraction has increased much in recent years, it is now possible to begin to explain, in some detail, how the contractile activity may be modulated. A detailed account of the mechanism of contraction in the uterus is therefore given, followed by examples of modulation of this process for each of the four physiological methods listed above. Examples have been chosen to illustrate either general or particular mechanisms of modulation. The goal of many working in this field is to understand these processes and thus prevent preterm labor and uterine dysfunction in term labor, which are still significant clinical problems. PMID- 8430760 TI - Agonist activation modulates cross-bridge states in single vascular smooth muscle cells. AB - To determine cross-bridge properties during agonist-stimulated contractions, steady-state force and relative steady-state stiffness were recorded at rest (pCa 9) and during both full (pCa 4) and partial (pCa 7) Ca2+ activations of isolated single alpha-toxin permeabilized vascular smooth muscle cells. For pCa 4 and pCa 7, agonist (1 microM histamine) activation resulted in significant (P < 0.05) increases in both force and stiffness. The agonist-induced increase of steady state force was significantly (P < 0.05) greater than that of stiffness; at pCa 4, there was a 48% increase for force vs. 17% for stiffness, and, at pCa 7, there was a 160% increase for force vs. 57% for stiffness. The increase in force and stiffness after agonist prestimulation implies that the number of attached cross bridges has increased. However, after agonist prestimulation, we found that the increase of force was greater (P < 0.05) than that of stiffness, resulting in a greater force at any given level of stiffness. Thus these data indicate that agonist activation, presumably via activation of a G protein, increases the relative force per attached cross bridge, possibly by modulating the kinetics of the actomyosin adenosinetriphosphatase to increase in the relative population of cross bridges in force-producing states [actinomyosin (AM) or AM.ADP]. PMID- 8430761 TI - Dietary n-3 and n-6 fatty acids are equipotent in stimulating volume regulation in Ehrlich ascites tumor cells. AB - This investigation addresses whether enriching cellular phospholipids with n-3 or n-6 fatty acids affects the process of regulatory volume decrease (RVD) in murine Ehrlich ascites tumor cells. Two weeks of dietary n-3-rich fish oil (7.5%, wt/wt) increased the ratio of eicosapentaenoic acid to arachidonic acid in cellular phospholipids compared with an olive oil control diet. Cells grown in mice fed on fish oil had an accelerated RVD response after hypotonic exposure, indicating that the volume-induced K+ conductance was increased. The fish oil diet furthermore resulted in an increased Cl- conductance during RVD, demonstrated as an increased initial rate of cell shrinkage after addition of K+ ionophore to the swollen cells. The initial rate of volume recovery correlated positively with the sum of eicosanoid precursors (arachidonic acid plus eicosapentaenoic acid) (P = 0.007). Diet supplemented with n-6 fatty acids resulted in an enhanced RVD response as well. RVD was inhibited by anti-calmodulin drugs, and exogenous leukotriene D5 and leukotriene D4 were equipotent in attenuating this inhibition. We conclude that dietary polyunsaturated fatty acids result in a more effective RVD response because of an increase in the volume-induced Cl- and K+ conductances. We propose that this is caused by an enhanced volume-induced leukotriene synthesis due to an increase in eicosanoid precursor availability. PMID- 8430762 TI - Amino acid loss during volume regulatory decrease in cultured chick heart cells. AB - Mechanisms of volume regulation in hyposomotically treated cultured chick heart cell preparations were studied using optical, biochemical, and nuclear magnetic resonance methods. This approach afforded the resolution of time-dependent responses that might ordinarily be obscured by the complex morphology of intact cardiac muscle preparations. In hyposmotic solutions, cells swelled to a peak volume within 3 min and slowly regulated toward original volume (regulatory volume decrease, RVD). Upon return of the cells to isosmotic solution following hyposmotic treatment, the cells shrank to a steady-state volume that was substantially less than the initial volume in control solution. A vigorous RVD could also be elicited by hyposmotic swelling under Cl(-)-free conditions. Measurement of both inorganic cation loss via atomic absorption spectroscopy and organic solute loss via 1H-nuclear magnetic resonance and high-pressure liquid chromatographic techniques revealed that the RVD observed following exposure to hyposomotic solutions was mediated in part by a substantial loss of taurine, glutamate, aspartate, and glycine as well as loss of inorganic ions (Na+,K+). The hyposmotically activated transport of amino acids was also associated with the production of glutamate and aspartate. The volume regulatory release and production of amino acids have significant implications for the metabolic and functional integrity of cardiac cells. PMID- 8430763 TI - Adaptation of muscle to creatine depletion: effect on GLUT-4 glucose transporter expression. AB - Feeding rats beta-guanidinopropionic acid (beta-GPA), a creatine analogue, results in depletion of creatine and phosphocreatine and induces increases in mitochondrial oxidative enzymes and hexokinase in skeletal muscle. Comparisons of different muscle types and studies of the adaptation to exercise suggest that 1) the levels of the insulin-responsive glucose transporter (GLUT-4), mitochondrial oxidative enzymes, and hexokinase may be coregulated and 2) GLUT-4 content can determine maximal glucose transport activity in muscle. To further evaluate these possibilities, we examined the effects of feeding rats 1% beta-GPA in their diet for 6 wk on muscle GLUT-4 expression and glucose transport activity. beta-GPA feeding induced 40-50% increases in cytochrome c concentration, citrate synthase activity, and hexokinase activity in plantaris muscle. GLUT-4 protein concentration was increased approximately 50% in plantaris and epitrochlearis muscles, while GLUT-4 mRNA was increased approximately 40% in plantaris muscles of beta-GPA-fed rats. Glucose transport activity maximally stimulated by insulin was increased in parallel with GLUT-4 protein concentration in the epitrochlearis. These results provide evidence that chronic creatine depletion increases GLUT-4 expression by pretranslational mechanisms. They support the hypothesis that the levels of mitochondrial enzymes, hexokinase, and GLUT-4 protein are coregulated in striated muscles. They also support the concept that the GLUT-4 content of a muscle determines its maximal glucose transport activity when the signaling pathways for glucose transport activation are intact. PMID- 8430764 TI - Altering creatine kinase isoenzymes in transgenic mouse muscle by overexpression of the B subunit. AB - To change the levels of expression and isoenzyme distribution of creatine kinase (CK) in muscle, transgenic technology was used to express the B subunit of CK in mouse muscle. Normally, mammalian skeletal muscle contains the MM dimer of CK. The BB dimer and MB heterodimer of CK can be found in brain and heart, respectively. Heterologous genes consisting of skeletal and cardiac muscle specific actin promoters fused to the genomic coding region of the B form of CK were used to create transgenic mice. Lines were established from the three highest expressing founders. Analysis of skeletal muscle extracts revealed that all three lines had an increase in total CK activity measured under maximal velocity conditions. The highest expressing line, 7001, had a CK activity 150% that of control muscle. Nuclear magnetic resonance saturation transfer was used to measure the in vivo rate of the CK reaction. In 7001 hindlimb muscles, the CK catalyzed reaction was 200% that of control muscle. The elevation in CK activity in transgenic muscle was accompanied by significant changes in the composition of the cytosolic isoenzyme ratio of CK. In control, 100% of CK was MM, whereas 7001 had 60 +/- 18% MM, 32 +/- 10% MB, and 8 +/- 2% BB. There were no changes in ATP, phosphocreatine, Pi, or creatine levels in transgenic muscle compared with control. Immunofluorescence of myofibrils isolated from control and transgenic muscle revealed specific association of CK to the M line. Small amounts of MB CK were detected on myofibrils from transgenic mice. Transgenic mice expressing the B subunit of CK in muscle represent a first step toward altering CK isoforms so as to elucidate the specific roles of these isoforms in energy metabolism. PMID- 8430765 TI - Morphological and biochemical analysis of angiotensin II internalization in cultured rat aortic smooth muscle cells. AB - The intracellular pathway and kinetics of angiotensin II (ANG II) internalization are not well understood. We developed a biologically active ANG II-colloidal gold complex to qualitatively examine, by transmission electron microscopy, the ultrastructural details of ANG II binding and internalization in cultured rat aortic vascular smooth muscle cells (VSMC). To quantitatively evaluate ANG II internalization, we analyzed intracellular accumulation of 125I-labeled ANG II. These studies show that ANG II is internalized by VSMC in a time- and temperature dependent fashion with a half time of < 2 min at 37 degrees C. Initially, ANG II binds diffusely over the entire cell surface. After binding, the ANG II receptors aggregate in coated pits that transform into small intracellular vesicles. By 60 min after internalization, gold particles are evident within large lysosome-like vesicles deep within the cell. ANG II-gold binding and internalization were selective: control probe (no ANG II) did not internalize; losartan potassium effectively competed for ANG II-gold binding and internalization. PMID- 8430767 TI - Force-length relation of isometric sarcomeres in fixed-end tetani. AB - The higher force observed in fixed-end tetani relative to sarcomere-isometric tetani is commonly attributed to sarcomere length inhomogeneity; sarcomeres in the end regions of the fiber shorten extensively at the expense of the central sarcomeres. By shortening, these sarcomeres supposedly attain higher force production capacity and can thus account for the extra force. However, the fibers could also contain sarcomeres that stay isometric throughout most of the tetanic force plateau. If such sarcomeres undergo slight shortening before their isometric phase, their force-length relation should be elevated (A. Horowitz, H. P. M Wussling, and G. H. Pollack. Biophys. J. 63: 3-17, 1992). These sarcomeres may therefore account for the higher force in fixed-end tetani. To test this possibility, single frog semitendinosus fibers were tetanized under fixed-end conditions. Sarcomere length change during the tetanus was measured at different locations along the fiber by optical diffraction. Fibers stretched to average sarcomere lengths between 2.2 and 3.2 microns contained sarcomeres that, except for some initial shortening during the early part of the tetanus, remained isometric. These sarcomeres were located between the ends and the central region of the fibers. Their force-length relation was higher than the linear force length relation based on sarcomere length clamps by an average of 14% between sarcomere lengths of 2.4-3.2 microns. Thus slight (1-5%) shortening may explain the relatively higher fixed-end force-length relation. PMID- 8430766 TI - Dual mechanisms for Na-K-Cl cotransport regulation in airway epithelial cells. AB - To investigate cellular mechanisms involved in the regulation of basolateral Na-K Cl cotransport in airway epithelia, we determined saturable basolateral [3H]bumetanide binding, a measure of functioning cotransporters, in primary cultures of canine tracheal and human nasal epithelial cells, including cells from patients with cystic fibrosis (CF). As we previously reported [M. Haas, L. G. Johnson, and R. C. Boucher. Am. J. Physiol. 259 (Cell Physiol. 28): C557-C569, 1990], isoproterenol and hypertonic cell shrinkage produce an equivalent stimulation of [3H]bumetanide binding to dog tracheal cells. We now find that apical ATP and UTP, which stimulate apical Cl channels and Cl secretion in normal and CF airway cells by an adenosine 3',5'-cyclic monophosphate (cAMP)-independent mechanism (S. J. Mason, A. M. Paradiso, and R. C. Boucher. Br. J. Pharmacol. 103: 1649-1656, 1991), increase basolateral [3H]bumetanide binding to dog tracheal cells to the same extent as do isoproterenol and hypertonic shrinkage. The stimulatory effects of ATP and UTP on binding are inhibited by apical addition of a Cl channel blocker, the indanyloxyacetic acid derivative IAA-94 (0.2 mM), or by raising basolateral K concentration ([K]b) from 3.3 to 40 mM, suggesting these effects are secondary to apical Cl efflux via channels. Apical IAA-94 and increased [K]b also inhibit stimulation of binding by isoproterenol by approximately 50%, suggesting that part (but not all) of the effect of the beta agonist on basolateral cotransport is secondary to apical Cl efflux, with an additional component of direct stimulation of cotransport via cAMP. In support of this interpretation, we find that isoproterenol and a membrane-permeable cAMP analogue increase [3H]bumetanide binding to primary cultures of CF nasal epithelial cells, in which significant cAMP-mediated stimulation of apical Cl efflux does not occur. [3H]bumetanide binding to CF nasal cells is also stimulated by apical ATP, and levels of saturable [3H]bumetanide binding to CF cells are 1.3-1.5 times those in non-CF nasal cells under both basal and stimulated conditions. The results suggest that basolateral Na-K-Cl cotransport in airway cells may be upregulated in two distinct ways: 1) directly via a cAMP dependent cascade, and 2) as a secondary response to apical Cl channel activation. Both of these mechanisms appear to be intact in CF. PMID- 8430768 TI - Lateral diffusion of lipids in renal cells: effects of hypoxia and reoxygenation and role of cytoskeleton. AB - The effects of hypoxia and reoxygenation on the lateral mobility of membrane lipids were studied in primary cultures of rat proximal tubule epithelial cells at a subconfluent stage. The lipid lateral diffusion coefficient (DL) of the fluorescent probe 1-acyl-2-(N-4-nitrobenzo-2-oxa-1,3-diazol)-aminocaproyl phosphatidylethanolamine was determined in membranes of attached cells by the technique of fluorescence redistribution after photobleaching, using confocal imaging to differentiate apical from basal surfaces. Fluidity was greater in basolateral membranes than in apical membranes [DL(apical) = 3.15 +/- 0.8 and DL (basolateral) = 6.56 +/- 1.2 x 10(-10) cm2/s]. In apical membranes, 60 min of hypoxia plus 30 min of reoxygenation increased DL to 10.04 +/- 2.1. When cells were pretreated with the antioxidants superoxide dismutase, catalase, or alpha tocopherol, there was no clear-cut effect on the hypoxia-reoxygenation-induced increase in apical membrane DL, although t-butyl hydroperoxide treatment of cells did increase DL. Disruption of the cytoskeleton with cytochalasin D or exposure to Ca(2+)-free medium markedly increased DL. However, when cells were pretreated with phallacidin to stabilize cytoskeletal actin microfilaments, the hypoxia reoxygenation-induced change in lipid lateral mobility was completely prevented. Thus the cytoskeleton is an important regulator of the translational motion of membrane phospholipids. Hypoxia-reoxygenation may have increased DL because of cytoskeletal dysfunction. PMID- 8430769 TI - Mechanisms of ATP conservation during ischemia in slow and fast heart rate hearts. AB - In the present study we compared the quantitatively most important, Pi-activated mechanisms for conserving ATP during ischemia in dog and rat cardiac muscle. Earlier studies by ourselves showed that dog heart, like all slow heart rate mammalian hearts examined, possesses the ability to inhibit its mitochondrial ATPase by binding IF1, the ATPase inhibitor protein, during ischemia. Rat heart, like other fast heart rate mammalian hearts studied, does not. The present study demonstrated that this IF1-mediated ATPase inhibition in ischemic dog heart, as in other slow heart rate hearts, appears to depend on matrix space acidification mediated largely by Pi-H+ symport via the mitochondrial Pi carrier. The present study further confirmed that maximal glycolytic flux rates are five- to sixfold greater in ischemic rat than in ischemic dog heart. Both of these systems are activated by increasing Pi concentration ([Pi]) during ischemia, and both appear to be regulated somewhat differently in dog than in rat heart. Thus intact dog heart mitochondria exhibited a [Pi]-dependent ATPase inhibition at low external pH, whereas rat heart mitochondria did not. The [Pi] required for maximal ATPase inhibition in dog heart mitochondria was approximately 6 mM. Although both dog and rat heart phosphofructokinase were stimulated by Pi, the enzyme in dog heart was maximally activated by approximately 6 mM Pi, whereas the rat heart enzyme required only approximately 3 mM Pi for its maximal stimulation under otherwise identical conditions. The most active nonmitochondrial ATPase in ischemic dog and rat cardiac muscle, the Ca(2+)-activated actomyosin ATPase, accounted for approximately one-half of the total nonmitochondrial ATPase activity in each species.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430770 TI - Adrenergically activated Ca2+ increases in brown fat cells: effects of Ca2+, K+, and K channel block. AB - We measured intracellular calcium concentration ([Ca2+]i) during adrenergic stimulation using fura-2 ratio imaging of individual cultured neonatal rat brown fat cells. One micromolar norepinephrine (NE) increased [Ca2+]i from an average resting value of 105 nM to 555 nM in approximately 30 s. [Ca2+]i remained elevated as long as NE was present but returned to resting levels within 2-3 min after NE removal. The response was half maximal at approximately 50 nM NE and was primarily alpha-adrenergic. The sustained, but not the initial, increase in [Ca2+]i required extracellular calcium. Cells stimulated in high-K media had [Ca2+]i responses like those in 0 Ca2+, suggesting that depolarization abrogates calcium influx. Parallel perforated-patch recordings showed that the increase in [Ca2+]i activates a calcium-activated K conductance. Blocking K channels with moderate concentrations of tetraethylammonium (TEA) had only small effects on NE induced changes in [Ca2+]i, but high concentrations of TEA significantly reduced the response. We conclude that cytoplasmic calcium is modulated by fluxes from both intracellular and extracellular sources and that K channels may not be required for normal short-term [Ca2+]i responses to hormone. PMID- 8430771 TI - Maintenance of contractility in dissociated smooth muscle: low-density cultures in a defined medium. AB - The loss of contractility in long-term cultures of dissociated smooth muscle is such an established observation that the lack of contractility of cultured smooth muscle cells is often not even noted. This report describes methods of dissociating and culturing smooth muscle cells from the avian amnion that maintain contractility for > 1 mo in a defined medium. Because contractility was assessed by monitoring the contractions of individual cells to neurotransmitter related substances, it is clear that these cells maintained both contractility and pharmacological responsiveness. However, when amniotic smooth muscle cells were dissociated with enzymes containing impurities or cultured in the presence of serum, they flattened and lost contractility, as reported for many other types of smooth muscle. PMID- 8430772 TI - Tyrosine kinase regulates epithelial sodium transport in A6 cells. AB - Insulin increases epithelial Na+ reabsorption, and many of its actions involve tyrosine kinase. We used tyrosine kinase inhibitors to examine the role of tyrosine kinase in the action of insulin. Pretreatment of Na+ transporting cells with tyrosine kinase inhibitors attenuates the subsequent action of insulin, suggesting that the action of insulin on epithelial Na+ transport involves tyrosine kinase activity. In addition to their effect on insulin-induced Na+ transport, the tyrosine kinase inhibitors also significantly reduce Na+ transport in Na(+)-transporting epithelial cells, suggesting that there is a significant tonic tyrosine kinase activity that modulates epithelial Na+ transport. Using patch-clamp methods, we found that one inhibitor, genistein, reduces the number of active Na+ channels in cell-attached patches without significantly affecting the open probability of any remaining channels. The effects of the tyrosine kinase inhibitors are not due to inhibition of protein kinase A (PKA), since H89, a PKA inhibitor, does not affect Na+ transport of control cells (as the tyrosine kinase inhibitors do), and the tyrosine kinase inhibitor, genistein or tyrphostin 23, does not alter the stimulation of ion transport by 8-(4 chlorophenylthio)adenosine 3',5'-cyclic monophosphate, a membrane-permeable adenosine 3',5'-cyclic monophosphate analogue (as H89 does). PMID- 8430773 TI - Acute exposure to cholesterol increases arterial nitroprusside- and endothelium mediated relaxation. AB - The effect of cholesterol enrichment on arterial relaxation was studied by evaluating sodium nitroprusside (SNP)- and endothelium-mediated relaxation of isolated rabbit carotid artery. Arterial segments were perfused in vitro (4 h) with cholesterol-rich liposomes consisting of free cholesterol (FC) and phospholipid (PL) in a 2:1 molar ratio. Ring segments from arteries exposed to cholesterol-rich liposomes exhibited a 60% increase (P < 0.01) in FC content without affecting PL content. Cholesterol-enrichment was associated with a twofold increase (r = 0.92, P < 0.05) in acetylcholine- and A23187-induced endothelium-mediated relaxation. Bioassay of endothelium-derived relaxing factor(s) (EDRF) after cholesterol exposure indicated that EDRF half-life and/or release increased (P < 0.05) threefold. A trend (P = 0.07) toward increased smooth muscle cell sensitivity to EDRF after cholesterol enrichment was also observed. Cholesterol enrichment increased (P < 0.05) sensitivity to SNP 12-fold, and this difference was further augmented (P < 0.01) twofold with endothelium removal. Cholesterol enrichment had no effect on relaxation to N2,2'-O dibutyrylguanosine 3',5'-cyclic monophosphate. These data indicate that acute cholesterol enrichment increases EDRF activity from arterial endothelium and increases smooth muscle responses to both EDRF and SNP. PMID- 8430774 TI - Adenosine stimulation of AMP deaminase activity in adult rat cardiac myocytes. AB - Using an in situ assay for analyzing AMP deaminase activity in isolated adult rat ventricular myocytes, we have shown that IMP production is stimulated approximately twofold in cardiac cells incubated with 10 microM adenosine. This effect of adenosine was not blocked by the adenosine A1-receptor antagonist 8 cyclophenyl-1,3-dipropylaxanthine (0.01-1 microM) except at a concentration (100 microM) that may inhibit adenosine transport. Similarly, in situ AMP deaminase activity was not enhanced by treatment with the specific adenosine A1-receptor agonists N6-phenylisopropyl adenosine or cyclopentyladenosine, nor was it sensitive to prior treatment of cells with pertussis toxin. The nucleoside transport blockers S-4-nitrobenzyl-6-thioinosine, dipyridamole, and papaverine inhibited adenosine-induced increases in IMP production by 75-85%, suggesting an intracellular site of action. Modulation of enzyme activity via the transmethylation pathway could not be implicated since incubation of cardiac cells under conditions known to elevate intracellular S-adenosyl-L-homocysteine had no demonstrable effect on AMP deaminase. Furthermore, a direct allosteric effect of adenosine on the partially purified rat cardiac enzyme was not observed. The results indicate that intracellular adenosine modulates rat cardiac AMP deaminase by an unknown mechanism. PMID- 8430775 TI - PDGF-induced mitogenic signaling is not mediated through protein kinase C and c fos pathway in VSM cells. AB - This study examines the role of protein kinase C (PKC) in platelet-derived growth factor (PDGF)-induced vascular smooth muscle (VSM) cell proliferation and initial signaling events. A 24-h pretreatment of VSM cells with 200 nM phorbol 12 myristate 13-acetate (PMA) completely abolished immunologically reactive PKC activity. Depletion of PKC activity from VSM cells did not attenuate PDGF stimulated [3H]thymidine incorporation compared with control cells. Similarly, acute activation of PKC by treatment with 200 nM PMA for 10 min had no effect on PDGF-mediated [3H]thymidine incorporation. Both PMA and PDGF increased c-fos induction to the same magnitude; however, treatment with PMA did not induce DNA synthesis in these cells. In PKC-depleted cells PDGF-mediated c-fos induction was reduced by 50-60%, while DNA synthesis in response to PDGF stimulation was not reduced. PKC depletion did not alter PDGF-stimulated increase in cytosolic calcium levels, 125I-PDGF binding, or receptor autophosphorylation. On the basis of these results, we conclude that PKC activation and c-fos induction do not play a significant role in PDGF-mediated mitogenesis in VSM cells. PMID- 8430776 TI - Immunofluorescent localization of the ubiquitin-activating enzyme, E1, to the nucleus and cytoskeleton. AB - Ubiquitin, a 76-amino acid protein, is covalently attached to abnormal and short lived proteins, thus marking them for ATP-dependent proteolysis in eukaryotic cells. Ubiquitin is found within the cytoplasm, nucleus, microvilli, autophagic vacuoles, and lysosomes. The ubiquitin-activating enzyme, E1, catalyzes the first step in ubiquitin conjugation. To date, very little is known about the subcellular distribution of this enzyme. We have utilized immunofluorescence and immunoblotting to examine the cellular distribution of E1 in several eukaryotic cell lines, including HeLa, smooth muscle A7r5, choriocarcinoma BeWo, Pt K1, and Chinese hamster ovary (CHO) E36. E1 was identified in both cytoplasmic and nuclear compartments in all cell lines examined. However, the relative abundance within these compartments differed markedly between the cell lines. Even within a single cell line, nuclear distribution was not uniform, and certain cells demonstrated an absence of nuclear staining. E1 resides predominantly within the nucleus in BeWo. In contrast, its distribution in CHO and Pt K1 cells is mainly cytoplasmic. Within the cytoplasm, three pools of E1 were identified by double label immunofluorescence. The first of these colocalized with phalloidin, indicating association of E1 with actin filaments. A second cytoplasmic pool colocalized with tubulin and was predominantly perinuclear in its distribution. The third pool associated with intermediate filaments. This suggests that E1 is associated with all three components of the cytoskeleton. The distribution of E1 was unaltered in a mutant line of CHO E36 designated ts20, in which the E1 can be thermally inactivated. The variable distribution of E1 among cell lines, including its apparent cytoskeletal association, suggests pleiotropic functions of this enzyme and the ubiquitin-conjugating system. PMID- 8430777 TI - Multiple metabolic effects of CGRP in conscious rats: role of glycogen synthase and phosphorylase. AB - Calcitonin gene-related peptide (CGRP) is a neuropeptide that is released at the neuromuscular junction in response to nerve excitation. To examine the relationship between plasma CGRP concentration and intracellular glucose metabolism in conscious rats, we performed insulin (22 pmol.kg-1.min-1) clamp studies combined with the infusion of 0, 20, 50, 100, 200, and 500 pmol.kg-1.min 1 CGRP (plasma concentrations ranging from 2 x 10(-11) to 5 x 10(-9) M). CGRP antagonized insulin's suppression of hepatic glucose production at plasma concentrations (approximately 10(-10) M) that are only two- to fivefold its basal portal concentration. Insulin-mediated glucose disposal was decreased by 20-32% when CGRP was infused at 50 pmol.kg-1.min-1 (plasma concentration 3 x 10(-10) M) or more. The impairment in insulin-stimulated glycogen synthesis in skeletal muscle accounted for all of the CGRP-induced decrease in glucose disposal, while whole body glycolysis was increased despite the reduction in total glucose uptake. The muscle glucose 6-phosphate concentration progressively increased during the CGRP infusions. CGRP inhibited insulin-stimulated glycogen synthase in skeletal muscle with a 50% effective dose of 1.9 +/- 0.36 x 10(-10) M. This effect on glycogen synthase was due to a reduction in enzyme affinity for UDP glucose, with no changes in the maximal velocity. In vitro CGRP stimulated both hepatic and skeletal muscle adenylate cyclase in a dose-dependent manner. These data suggest that 1) CGRP is a potent antagonist of insulin at the level of muscle glycogen synthesis and hepatic glucose production; 2) inhibition of glycogen synthase is its major biochemical action in skeletal muscle; and 3) these effects are present at concentrations of the peptide that may be in the physiological range for portal vein and skeletal muscle. These data underscore the potential role of CGRP in the physiological modulation of intracellular glucose metabolism. PMID- 8430778 TI - Regulation of eukaryotic initiation factor-2B activity in muscle of diabetic rats. AB - Peptide-chain initiation is inhibited in fast-twitch skeletal muscle, but not heart, of diabetic rats. We have investigated mechanisms that might maintain eukaryotic initiation factor (eIF)-2B activity, preventing loss of efficiency of protein synthesis in heart of diabetic rats but not in fast-twitch skeletal muscle. There was no change in the amount or phosphorylation state of eIF-2 in skeletal or cardiac muscle during diabetes. In contrast, eIF-2B activity was decreased in fast-twitch but not slow-twitch muscle from diabetic animals. NADP+ inhibited partially purified eIF-2B in vitro, but addition of equimolar NADPH reversed the inhibition. The NADPH-to-NADP+ ratio was unchanged in fast-twitch muscle after induction of diabetes but was increased in heart of diabetic rats, suggesting that NADPH also prevents inhibition of eIF-2B in vivo. The activity of casein kinase II, which can phosphorylate and activate eIF-2B in vitro, was significantly lower in extracts of fast-twitch, but not cardiac muscle, of diabetic rats compared with controls. The results presented here demonstrate that changes in eIF-2 alpha phosphorylation are not responsible for the effect of diabetes on eIF-2B activity in fast-twitch skeletal muscle. Modulation of casein kinase II activity may be a factor in the regulation of protein synthesis in muscle during acute diabetes. The activity of eIF-2B in heart might be maintained by the increased NADPH/NADP+. PMID- 8430779 TI - Splanchnic bed utilization of leucine and phenylalanine in humans. AB - To study the fate of enterally delivered essential amino acids, leucine and phenylalanine, 14 healthy adults were infused in the postabsorptive state with [1 13C]leucine, [5,5,5-2H3]leucine, and [phenyl-2H5]phenylalanine for 7 h in a crossover design by intravenous and nasogastric tube routes. The amount of enterally delivered tracer that was sequestered by the splanchnic bed on the first pass was 21 +/- 1, 17 +/- 3, and 29 +/- 2 for the [13C]leucine, [2H]leucine, and [2H]phenylalanine tracers, respectively. Less than 2% of the nasogastric [1-13C]leucine tracer was oxidized on the first pass. We estimate that 40% of the nasogastric leucine tracer that was sequestered on the first pass was converted to alpha-ketoisocaproate and released, and 50% was incorporated into newly synthesized proteins. Assuming that less phenylalanine is incorporated into protein than leucine because of the lower abundance of phenylalanine in protein compared with leucine, we estimate that 80% of the extracted nasogastric phenylalanine tracer was converted to tyrosine. The study design also indicated a significant effect of duration of tracer infusion on the results, presumably due to recycling of tracer from rapidly turning over protein. PMID- 8430780 TI - Effects of chronic elevation in plasma cortisol on hepatic carbohydrate metabolism. AB - This study was undertaken to investigate the effects of chronic physiological elevations in plasma cortisol on glycogenolysis and gluconeogenesis in conscious, overnight-fasted dogs. Experiments consisted of an 80-min tracer and dye equilibration period and a 40-min sampling period. Infusions of D-[3-3H]glucose, L-[U-14C]alanine, and indocyanine green dye were used to assess glucose production (Ra) and gluconeogenesis using tracer and arteriovenous (a-v) difference techniques. In the cortisol group, (n = 10), a continuous infusion of hydrocortisone (3.5 micrograms.kg-1 x min-1) was begun 5 days before the experiment and continued throughout the sampling period. In the saline group (n = 10), there was no infusion of cortisol. The fivefold elevation in plasma cortisol increased plasma insulin from 12 +/- 2 to 19 +/- 2 microU/ml. Glucose Ra was elevated in the cortisol group (3.5 +/- 0.2 vs. 2.8 +/- 0.2 mg.kg-1 x min-1) but net hepatic glucose output was markedly diminished (1.2 +/- 0.4 vs. 2.7 +/- 0.3 mg.kg-1 x min-1). Gluconeogenic conversion of alanine to glucose was increased slightly by cortisol (0.60 +/- 0.13 to 0.99 +/- 0.12 mumol.kg-1 x min-1), but the gluconeogenic efficiency of the liver was unchanged. Cortisol increased hepatic glycogen content evident at the end of the study greater than twofold (76.4 +/- 7.9 vs. 30.0 +/- 4.7 g/liver). These results suggest that cortisol 1) promotes glucose cycling through glycogen, 2) greatly inhibits nonhepatic glucose utilization, 3) increases hepatic gluconeogenesis in vivo primarily through enhanced substrate delivery to the liver, and 4) raises plasma insulin levels, which restrains intrahepatic gluconeogenesis. PMID- 8430781 TI - Estimation of protein fractional synthetic rate from tracer data. AB - The fractional synthetic rate (FSR) is a key parameter characterizing protein turnover that is estimated from tracer kinetic data. Formulas to estimate this parameter usually assume a precursor-product model. Assuming this model is correct, we discuss these formulas to estimate the FSR in the steady and non steady state both for the radioactive and stable isotope tracer. Then we deal with the non-steady-state case where the FSR becomes time varying and derive formulas for its estimation. A non-steady-state case study on the flooding-dose technique for measuring protein turnover is presented. PMID- 8430782 TI - Measurement of endogenous synthesis of plasma cholesterol in rats and humans using MIDA. AB - We used the mass isotopomer distribution analysis (MIDA) technique to measure endogenous synthesis of plasma cholesterol in vivo in rats and normal human subjects. Sodium [1-13C]- or [2-13C]acetate was infused, and plasma free cholesterol was analyzed by gas chromatography-mass spectrometry. Frequencies of mass isotopomers M0-M4 (mass-to-charge ratio 368-372) were quantified. The enrichment of the true precursor for cholesterol synthesis (acetyl-coenzyme A in contributing tissues) was determined using the MIDA method. This technique remains mathematically valid even if more than one tissue contributes to circulating free cholesterol. The fractional contribution (f) from endogenous synthesis to free cholesterol in normal women (n = 5) was 2.48 +/- 0.39% after 7 h in the postabsorptive state and 1.27 +/- 0.41% after 8 h of refeeding. In ad libitum-fed rats (n = 12), f was 2.89 +/- 0.44% after 12 h, whereas administration of recombinant tumor necrosis factor increased this value fourfold. Next, the rate constant (k) for removal of labeled free cholesterol from plasma was calculated. Higher masses (M2-M4) were followed to avoid the problem of persistent label incorporation. During the 60 h after cessation of [13C]acetate infusions, k was 0.02490 +/- 0.00298/h in humans. Using these values of k and f, absolute cholesterogenesis was 568 +/- 55 mg/day in normal women (follicular menstrual phase), similar to prior estimates based on whole body sterol balances. Women also exhibited a diurnal variation for endogenous cholesterol synthesis (34.6 +/- 5.4 mg/h nighttime vs. 15.9 +/- 5.2 mg/h daytime) consistent with current knowledge about rhythms in cholesterogenesis. Checks on the model were internally consistent (e.g., comparisons among different isotopomers for calculating precursor enrichment). We conclude that fractional and absolute endogenous cholesterol synthesis can be measured using stable isotopes in vivo by the MIDA technique. PMID- 8430783 TI - Studies on mechanisms of hepatic insulin resistance in cafeteria-fed rats. AB - Whether hyperinsulinemia causes insulin resistance or vice versa is controversial. The development of hyperinsulinemia and insulin resistance was tracked in the cafeteria-fed rat to determine which occurred first. After 3 days of cafeteria feeding the rats were obese, manifested a small but significant decrease in fasting glucose levels, and showed no change in fasting insulin levels, basal hepatic glucose production (HGP), insulin binding to hepatic membranes, and glucose utilization during a euglycemic hyperinsulinemic clamp, but the rats did demonstrate an increased glucose disappearance rate associated with an enhanced insulin response to intra-arterial glucose and hepatic insulin resistance during the clamp. After 7 days of cafeteria feeding, the results were similar except that fasting hyperglycemia and hyperinsulinemia, an enhanced basal HGP, and decreased insulin binding developed. After 6 wk of cafeteria feeding, both hepatic and peripheral insulin resistances were present. After 7 days of cafeteria feeding in rats given streptozotocin or etomoxir, an inhibitor of free fatty acid (FFA) oxidation, hepatic insulin resistance persisted despite elimination of hyperinsulinemia and reduction of FFA oxidation. These data do not support a causal role for either hyperinsulinemia or enhanced lipolysis of hypertrophied fat stores and subsequent FFA oxidation in the liver in the development of hepatic insulin resistance in this animal model of obesity. PMID- 8430784 TI - Effects of glucocorticoids on lymphocyte metabolism. AB - The immunosuppressive effect of glucocorticoids has been widely reported; however, the mechanism of action of these hormones on the immune system has not been fully established. In the present study, the effect of glucocorticoids on glucose, glutamine, and pyruvate metabolism in lymph node lymphocytes was investigated. Addition of dexamethasone to the incubation medium did not alter glucose and glutamine metabolism but inhibited pyruvate utilization by 40%. This latter effect took 1 h to occur and remained for up to 6 h, even after removal of dexamethasone from the culture medium. Measurements of the activity of pyruvate dehydrogenase in lymphocytes and the rate of [1-14C]-pyruvate conversion into 14CO2 in incubated lymphocyte mitochondria demonstrated that glucocorticoids decrease pyruvate utilization by inhibiting the activity of this key regulatory enzyme. The effect of such an inhibition of pyruvate utilization on the function of cells of the immune system remains to be clarified. PMID- 8430785 TI - Local cerebral glucose utilization in brains of lean and genetically obese (fa/fa) rats. AB - The local cerebral glucose utilization (LCGU) of brains from Wistar, lean Zucker (FA/FA), and obese Zucker (fa/fa) rats was investigated using the method of Sokoloff et al. (L. Sokoloff, M. Reiwich, C. Kennedy, M.H. Des Rosiers, C.S. Patlak, K.D. Pettigrew, O. Sakurada, and M. Shinohara. J. Neurochem. 28: 897-916, 1977.). The LCGU of obese Zucker (fa/fa) rats was decreased in comparison to the relatively high values obtained for the lean Zucker (FA/FA) rats in all gray matter areas studied, on average to the extent of 50%. When compared with Wistar rats, several brain areas of lean Zucker (FA/FA) animals had a normal glucose uptake. When these normal areas were assessed for common efferent and afferent pathways, it was found that many of these common connections had normal glucose utilizations. In direct comparison to the obese fa/fa rat, the LCGU rates of these areas were decreased, hinting that this would also be the case for their functional activity. Because these areas (limbic, thalamic, hypothalamic, autonomic) have been reported to be potentially relevant for bringing about the behavioral and neuroendocrine alterations known to occur in obese fa/fa rats, it is proposed that they represent dysfunctions that are partly responsible for the obesity syndrome of the fa/fa strain. PMID- 8430786 TI - Effects of thyroparathyroidectomy, parathyroid hormone, and PTHrP on kidneys of ovine fetuses. AB - The fetal parathyroid glands and parathyroid hormone-related protein (PTHrP) have been shown to be important regulators of fetal calcium metabolism through their actions on the placenta and bone. This study examined the effects of fetal thyroparathyroidectomy (with thyroxine replacement) and exogenous infusion of human parathyroid hormone [PTH-(1-34)], PTHrP-(1-34), and PTHrP-(1-141) on the urinary excretion of calcium in chronically cannulated ovine fetuses during the last one-fifth of gestation. Fetal plasma total and ionized calcium concentrations were significantly lower in thyroparathyroidectomized (TxPTx) fetuses when compared with intact fetuses, but there were no significant differences in urinary excretion rates of total calcium. However, TxPTx produced a significant increase in the fractional excretion rate of total calcium and a significant decrease in the excretion of adenosine 3',5'-cyclic monophosphate (cAMP) compared with intact fetuses. Infusions of PTH-(1-34), PTHrP-(1-34), and PTHrP-(1-141) into the jugular vein of TxPTx fetuses (n = 5) at the rate of 1 nmol/h for 2 h, after a 1-nmol loading dose, significantly decreased the excretion rate of total calcium and increased the excretion rate of cAMP in fetal urine. Infusions of all three peptides resulted in significant increases in the concentration of total calcium in fetal plasma but had no effect on the plasma concentrations or urinary excretion rates of phosphate. Infusion of either PTH-(1 34), PTHrP-(1-34), or PTHrP-(1-141) also resulted in an increase in fetal urine osmolality and pH and a decrease in free water clearance in TxPTx fetuses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430787 TI - Stepwise degradation of NT in pars convoluta and recta of rabbit proximal tubules: evidence of axial heterogeneity. AB - Reabsorption and degradation of the neuropeptide neurotensin (NT) in rabbit proximal pars convoluta (PC) and pars recta (PR) nephron segments were characterized. Brush-border membrane vesicle fractions (PC or PR) were incubated with [3H]NT, and the extent and pattern of peptide hydrolysis were determined by reversed-phase high-pressure liquid chromatography (rHPLC). Furthermore, isolated rabbit PC and PR segments were perfused with [3H]NT, reabsorption of [3H]NT was quantified, and the collected perfusate was analyzed by HPLC. Metabolites were characterized. Finally, rabbit proximal tubules were microinfused in vivo with [3H]NT to follow the tubular uptake by electron microscope autoradiography. Degradation increased with time in both vesicle fractions. The main difference was an extensive cleavage of NT in PR, as revealed by a higher proportion of end metabolites. This was also visualized as a higher proportion of the large degradation product in rHPLC fraction 39 [NT-(1-11)] in PC as compared with PR after 30 min of incubation. The isolated perfused proximal tubular segments processed NT with large efficiency. PC segments processed 90% of the perfused amount, and PR processed 88%. Only 13% in PC and 10% in PR of the processed NT were found in the bath and the tubule. The main part of processed NT was in the collected perfusate, and rHLPC profiles revealed that NT-(1-11) was the only metabolite in both PC and PR. Electron microscope autoradiography demonstrated autoradiographic grains over invaginations and over the apical part of the proximal tubule cell in endocytic vesicles and vacuoles 10 min after microinfusion of [3H]NT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430788 TI - Growth hormone response to GRF and insulin-induced hypoglycemia in Yorkshire and Meishan pigs. AB - Plasma glucose and porcine growth hormone (GH) responses to insulin and/or growth hormone-releasing factor (GRF) challenges were determined in Yorkshire (Y) and Meishan (MS) castrated male pigs at 140 days of age. The decline in glucose levels observed during the first 30 min after insulin injection was similar between the two breeds. In Y pigs, GH concentrations increased sharply after insulin injection. The GH response to insulin was much smaller in MS than in Y pigs (101 +/- 82 vs. 1,077 +/- 124 ng.min.ml-1, P < 0.001 after 0.30 U/kg insulin). The GH response to GRF (10 micrograms/kg) did not differ significantly between the two breeds. The GH response was larger after combined insulin (0.20 U/kg) plus GRF than after GRF alone in Y pigs (1,512 +/- 229 vs. 463 +/- 401 ng.min.ml-1, P < 0.05), whereas it did not differ in MS pigs (714 +/- 164 vs. 507 +/- 127 ng.min.ml-1, P > 0.10). The present data demonstrate that the GH response to insulin is dramatically altered in MS pigs. A possible explanation to this result is that somatostatin tone would not be depressed by insulin-induced hypoglycemia in MS pigs. PMID- 8430789 TI - Carbohydrate metabolism during pregnancy in control subjects and women with gestational diabetes. AB - The purpose of this study was to characterize carbohydrate metabolism associated with the development of gestational diabetes. Six control (Ctl) and ten women with gestational diabetes mellitus (GDM) were evaluated using an intravenous glucose tolerance test and hyperinsulinemic-euglycemic clamp with [6,6 2H2]glucose prior to conception (P) and at 12-14 (E), and 34-36 wk of gestation (L). There was an increase (P = 0.0001) in first-phase insulin response in Ctl (P 174 +/- 133, E 388 +/- 120, and L 587 +/- 303 microU/ml) and GDM (P 197 +/- 94, E 267 +/- 77, and L 376 +/- 162 microU/ml) but a significant (P = 0.02) lag in change in GDM with advancing gestation. Basal endogenous glucose production increased during gestation [Ctl: P 2.74 +/- 0.23, E 2.62 +/- 0.38, and L 3.14 +/- 0.36; GDM: P 2.68 +/- 0.51, E 2.78 +/- 0.45, and L 2.98 +/- 0.48 mg.kg fat-free mass (FFM)-1 x min-1; P = 0.02], but there was resistance to suppression by insulin infusion (P = 0.03) in late gestation (GDM: 0.61 +/- 0.44 vs. Ctl: 0.16 +/- 0.17 mg.kg FFM-1 x min-1). Insulin sensitivity decreased during gestation (Ctl: P 10.78 +/- 2.78, E 8.34 +/- 2.36, and L 4.75 +/- 1.22; GDM: P 7.49 +/- 2.13, E 7.40 +/- 1.45, and L 4.21 +/- 1.01 mg.kg FFM-1 x min-1; P = 0.0001) and was primarily decreased (P = 0.04) in GDM compared with Ctl from P through E. These findings closely resemble those of non-insulin-dependent, predominantly insulin-resistant diabetes, which is often a sequel of GDM. PMID- 8430790 TI - Control of electrogenic Na+ absorption in rat late distal colon by nanomolar aldosterone added in vitro. AB - It has been possible to obtain in a mammalian epithelium of dietetically and surgically untreated animals a dose response of in vitro-added aldosterone (Aldo, 10(-10) to 10(-5) M) on electrogenic Na+ absorption (JeNa). JeNa was measured in the Ussing chamber on stripped rat late distal colon 8 h after in vitro addition of Aldo. Submaximal effects were obtained at 3 nM Aldo; after a lag time of 2 h, short-circuit current (Isc) increased to a maximum of 234 +/- 15 microA/cm2 and dropped after 0.1 mM amiloride to -18 +/- 3 microA/cm2, resulting in JeNa of 9.4 +/- 0.6 mumol.h-1 x cm-1. Net Na+ tracer fluxes and Isc exhibited parallel time courses, so that electroneutral Na+ transport was not induced in late distal colon by acute Aldo. A plot of JeNa vs. Na conductance revealed an electromotive force (ENa) of 126 +/- 1 mV for all Aldo concentrations tested. Kinetic data were as follows: Michaelis constant 1.2 nM, maximal velocity (Vmax) 10.5 mumol.h-1 x cm-2, and Hill coefficient 2.1. In contrast to the large effect in late distal colon, 3 nM Aldo caused JeNa of < 1 mumol.h-1 x cm-2 in early distal colon, proximal colon, and cecum. Antimineralocorticoid sensitivity and ENa did not vary with Aldo concentration or time of the experiment, consistent with a unique mechanism during the early and late response up to 8 h, as well as at mineralocorticoid and glucocorticoid Aldo concentrations. Acute Aldo in a range of 0.1-10 nM fully controls JeNa between zero and Vmax in late distal colon.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430791 TI - Platelet-activating factor stimulates resorption by rabbit osteoclasts in vitro. AB - We have shown previously that platelet-activating factor (PAF), a potent inflammatory mediator, acts directly on isolated rat osteoclasts to elevate cytosolic free Ca2+ concentration ([Ca2+]i). The purpose of this study was to examine the effects of PAF on osteoclast function. Osteoclasts were isolated from the long bones of neonatal rabbits and studied in three ways. [Ca2+]i of fura-2 loaded osteoclasts was monitored by microspectrofluorimetry. In 9 out of 16 cells tested, PAF (10-100 nM) caused elevation of [Ca2+]i that peaked then returned to baseline. In contrast, the biologically inactive precursor and metabolite of PAF, lyso-PAF, was without effect. Using time-lapse videomicroscopy, we found that PAF elicited retraction of peripheral pseudopods. Although calcitonin induced sustained retraction and immobility, the response to PAF was transient and, within 30 min, pseudopods reformed. To assess effects of PAF on resorptive activity, osteoclasts were cultured on dentin slices for 48 h in the presence of vehicle, PAF (200 nM), or calcitonin (100 ng/ml). PAF increased the area of individual resorption pits (from control values of 1,660 +/- 110 to 2,240 +/- 200 microns2, P < 0.05) and the total planar area resorbed per unit area of substrate (from 7.6 +/- 1.6 to 14.5 +/- 3.1 x 10(4) microns2/cm2, P < 0.025). As expected, calcitonin significantly decreased resorptive activity. These data indicate that PAF activates osteoclastic resorption. PAF may play a role in mediating the resorption of bone and mineralized cartilage in inflammatory diseases such as rheumatoid arthritis and periodontitis. PMID- 8430792 TI - Thyroxine and triiodothyronine distribution and metabolism in thyroxine-replaced athyreotic dogs and normal humans. AB - Reported parenteral L-thyroxine (T4) replacement doses (10-20 micrograms.kg-1 x day-1) are larger than T4 production rates (2.5 micrograms.kg-1 x day-1) in athyreotic dogs but not humans. Furthermore, initial volumes of 3,5,3' triiodothyronine (T3) tracer distribution exceed those for T4 in both species. To evaluate these discrepancies, serum T4 and T3 tracer kinetic studies from T4 replaced athyreotic dogs (5 micrograms.kg-1 x day-1 sc) and euthyroid humans were analyzed in a three-pool model (rapidly and slowly equilibrating pools with serum). Dogs had lower total T4 (41%) and T3 (31%) and higher free fractions of T4 (432%) and T3 (456%) than humans. Initial T3 distribution volumes were 454% those for T4 in dogs and 149% in humans, 498% of predicted plasma volumes in dogs and 121-138% in humans. Thus plasma volumes were used as time 0 estimates for T3 data analysis. Dogs had higher fractional T4 and T3 transfer rates from serum to the rapid pools (440-451%), total T4 clearance (353%) and production rates (147%), similar total T3 clearance, but lower free T3 clearance (32%) and production rates (45%) than humans. These findings suggest: 1) higher fractional transfer rates of T4 and T3 from serum to tissues and total serum T4 clearance rates in dogs than humans relate to lower canine serum T4 and T3 binding, and 2) parenteral L-T4 replacement doses required to achieve upper-normal serum total T4 concentrations in athyreotic dogs (5 micrograms.kg-1 x day-1) correspond to T4 production rates (6.8 micrograms.kg-1 x day-1). PMID- 8430793 TI - Effects of aging on intestinal lipid absorption. AB - Because of the "graying" of the population there is increasing interest in age related changes in organ physiology. Impairment of lipid absorption, if present, could lead to malnutrition in the elderly while increased uptake of cholesterol could contribute to the rise in serum cholesterol levels seen in older individuals. This review critically analyzes the available information on age related changes in digestive and absorptive physiology of lipids. Overall, the data suggest that lipid digestion and absorption are, in general, well-preserved in aging. However, intercurrent illness or experimental stress may produce impairment in aging animals and humans that are not seen in younger controls. Areas deserving more detailed study are identified in this review and include intestinal motility, adaptation to stress, and assembly and transport of lipoproteins from enterocytes to lymph. PMID- 8430794 TI - Lactoferrin interferes with uptake of iron from transferrin and asialotransferrin by the rat liver. AB - Intravenous injection of bovine or human lactoferrin (6.25 x 10(-2) mumol/100 g body wt) in rats resulted in marked reduction of hepatic iron uptake from transferrin and asialotransferrin. The effect was dose dependent, saturable at approximately 5 mg/100 g body wt, and independent of lactoferrin's iron content. At this dose level, iron uptake from transferrin was reduced by 28% and from asialotransferrin by 43% in experiments lasting 90 min. Bovine lactoperoxidase, another basic protein, was similarly effective. The clearance of asialofetuin and pinocytosis of polyvinylpyrrolidone remained unaffected. Perfusion of isolated rat livers at 4 degrees C showed a strong reduction in asialotransferrin binding in the presence of lactoferrin. Chromatography of hepatic heparan sulfate proteoglycan on immobilized lactoferrin, lactoperoxidase, asialotransferrin, and transferrin showed that it possessed affinity for each of these proteins, more for the first two than the latter two. Heparan sulfate proteoglycan binding and efficacy in reducing hepatic iron uptake were also studied after selective modifications of positively charged amino acids in these proteins. The data obtained are compatible with the hypothesis that lactoferrin and other proteins with similarly high affinity for hepatic heparan sulfate exert their negative effect on iron uptake by preventing transferrin binding to the proteoglycan. The possibility is thus raised that the large number of low-affinity transferrin binding sites reported by earlier investigators for the liver may be heparan sulfate molecules. PMID- 8430795 TI - HCO3- reduces paracellular permeability of guinea pig duodenal mucosa by a Ca2+ (prostaglandin)-dependent action. AB - The mechanism of HCO3(-)-induced decrease in electrical conductance (Gt) of guinea pig duodenal mucosa was investigated in vitro. Gt and unidirectional fluxes of mannitol (M), Na+, and Cl- were straightly correlated. In the presence of HCO3- (20 mM), elevating the bath concentration of Ca2+ from 0 to 1.2 mM caused decreases in Gt and Na+ fluxes by approximately 30%. Smaller reductions were found in the absence of HCO-3. With the addition of Ca2+, Gt and unidirectional fluxes were lower with than without HCO3-. In the latter condition, PM/PNa, PM/PCl, and PNa/PCl (P is permeability) were close or equal to ratios predictable from free solution diffusion coefficients; with HCO3-, ratios became different or more different and PM/PNa was reduced. Straightly correlated were conductivities of six differently composed HCO3(-)-free salines and Gt of tissues bathed therein. This correlation did not embrace HCO3- Ringer. The Gt effect of Ca2+ (HCO3- present) was mimicked by prostaglandin E2 and reduced (by approximately 40%) by Ca2+ channel blockers (diltiazem, gallopamil), cyclooxygenase inhibitors (meclofenamate, diclofenac), cytochalasin D, and trifluoperazine. We conclude that without HCO3-, paracellular solute flow occurs mainly via structures resembling a free-solution shunt; HCO3-, through an action made more efficient by Ca(2+)-mediated prostaglandin synthesis and possibly involving microfilaments, strengthens a discriminatory barrier. PMID- 8430796 TI - ATP-sensitive potassium transport by pancreatic secretory granule membrane. AB - Electrolyte transport pathways in the pancreatic secretory granules may contribute to acini fluid production after fusion with the apical membrane. A component of this granule transport is a K(+)-selective pathway that has been measured indirectly by ionophore-induced lysis of the isolated secretory granules when suspended in a KCl solution. This granule membrane K+ transport was shown to be inhibited by physiological levels of ATP in a dose-dependent manner and was not reversed by ADP. The sulfonylurea tolbutamide (0.5 mM), a recognized inhibitor of ATP-sensitive K+ channels, also reduced the ionophore-dependent lysis by 46%. The ATP sensitivity of the K+ transport was influenced by pH (increased ATP sensitivity with decreasing pH) and KCl concentration (increased ATP sensitivity with increasing KCl). In addition, preincubation with phospholipase A2 (8.3 x 10(-10) g/ml) or lysophospholipids (6.7 x 10(-7) g/ml) produced a significant decrease in the granule K+ transport. However, it is not likely that this inhibition is due to a change in membrane fluidity, because fluidization with arachidonic acid or octanol did not have a comparable effect. The results then support a granule-associated K+ transport in pancreatic acinar cells and suggest that it is ATP and lysophospholipid sensitive. PMID- 8430797 TI - Ischemia-reperfusion in feline small intestine: a role for nitric oxide. AB - The objective of this study was to assess whether nitric oxide synthesis inhibition affects intestinal barrier function after ischemia-reperfusion of the feline small bowel. Local intra-arterial infusion of the nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 25 nmol.ml-1.min-1) was performed in autoperfused segments of cat ileum for 60 min after 90 min of ischemia and 60 min of reperfusion. Epithelial permeability was quantitated by measuring blood-to-lumen clearance of 51Cr-labeled EDTA, and microvascular dysfunction was assessed by measuring the clearance of protein from the vasculature into the interstitium. 125I-labeled albumin clearance from blood to lumen and histology were performed to further characterize the extent of intestinal dysfunction after reperfusion of the postischemic intestine in the presence and absence of L-NAME. Ischemia-reperfusion-induced mucosal and microvascular permeability increases were dramatically augmented by L-NAME infusion, and this effect was reversed by infusion of L-arginine (125 nmol.ml 1.min-1). Initiating L-arginine (but not D-arginine) infusion alone 10 min before reperfusion provided protection against ischemia-reperfusion-induced mucosal barrier dysfunction; however, this was not associated with a reduction in endogenous levels of L-arginine during ischemia-reperfusion. These data suggest that basal nitric oxide production is important in minimizing mucosal and microvascular barrier dysfunction associated with reperfusion of postischemic intestine. PMID- 8430798 TI - Protection against alkali injury to rabbit esophagus by CO2 inhalation. AB - Lye ingestion, a poisoning with no known effective treatment, frequently results in esophageal ulceration and healing by stricture formation. Tissue injury by lye is due to its alkalinity, and so therapy is logically directed at neutralization by acid. Here we describe a novel method, the inhalation of CO2, for the rapid delivery of (carbonic) acid capable of neutralizing tissue and luminal alkalinity. We also show that CO2 inhalation in anesthetized rabbits provides protection to the lye-exposed esophagus against transepithelial necrosis. This method has the potential to protect the human esophagus against lye injury, because it is relatively safe, rapidly effective, and can be administered in the field under emergency circumstances. PMID- 8430799 TI - Lipocytes from fibrotic rat liver have an impaired feedback response to procollagen propeptides. AB - Procollagen propeptides have been previously shown to be taken up by cultured fibroblasts and to inhibit collagen production at translational and transcriptional levels. In hepatic fibrosis, Ito cells are thought to be major contributors to collagen overproduction. We wondered whether an impaired response to procollagen propeptides by Ito cells from fibrotic liver could be a mechanism involved in collagen overproduction in hepatic fibrosis. In the presence of type I procollagen carboxy-terminal propeptide (200 nM), collagen production by Ito cells from normal rats was significantly decreased to 62.0% of control, whereas collagen production by Ito cells from two models of hepatic fibrosis in the rat, bile duct ligation and carbon tetrachloride treatment, was not significantly changed (102.4 and 102.6% of controls, respectively). By measurement of type I procollagen mRNA levels, this difference in response to procollagen carboxy terminal propeptide was determined to occur at a pretranslational level. The rates of uptake, transfer to the nuclear compartment, and degradation of procollagen propeptide were not significantly different in Ito cells from normal and fibrotic liver. PMID- 8430800 TI - Formation, absorption, and biotransformation of delta 6-lithocholenic acid in humans. AB - delta 6-Lithocholenic acid was identified in small amounts in fecal samples in vitro after incubation with ursodeoxycholic acid and in vivo in controls and after chenodeoxycholic and ursodeoxycholic acid ingestion. Fourteen to 45.0% of delta 6-[24-14C]lithocholenic acid was biotransformed in vitro in feces within 30 s. After colonic instillation of delta 6-[24-14C]lithocholenic acid, 50% of the radioactivity appeared in bile acids, most of it in lithocholic acid, within 3 h. Jejunal perfusions with delta 6-[24-14C]lithocholenic acid showed 33-92% absorption. One hour after jejunal instillation of 1 mmol, 4.4-27.5% of the biliary radioactivity was found in ursodeoxycholic, chenodeoxycholic, lithocholic, and 7-ketolithocholic acids. A sulfated glycine conjugate of delta 6 lithocholenic acid was identified in bile. One hour after intravenous injection of delta 6-[24-14C]lithocholenic acid, 40.1-42.6% of biliary radioactivity appeared in 7-ketolithocholic, chenodeoxycholic, lithocholic/isolithocholic, and ursodeoxycholic acids. The studies show that delta 6-lithocholenic acid is 1) formed in colonic lumen from chenodeoxycholic and ursodeoxycholic acids, 2) well absorbed in small intestine, and 3) biotransformed in both the colonic lumen and liver. The studies also identified delta 6-lithocholenic acid as a new intermediate in formation of lithocholic acid. Finally, the studies showed that a small portion of delta 6-lithocholenic acid is excreted as a sulfated glycine conjugate in bile. PMID- 8430801 TI - Regulation of secretion of pancreatic spasmolytic polypeptide from porcine pancreas. AB - We studied the neural and hormonal regulation of the secretion of pancreatic spasmolytic polypeptide (PSP), a potential growth factor, from isolated perfused porcine pancreas and the pancreatic exocrine secretion of PSP in response to a meal in young conscious pigs. PSP concentrations in the pancreatic juice ranged from 1 to 180 micrograms/ml. PSP released to the venous effluent amounted to 0.4 7% of the total output. Thus PSP is predominantly an exocrine product. Electrical vagal nerve stimulation increased PSP output 30-fold. Acetylcholine mimicked the effect of nerve stimulation, which was inhibited but not abolished by atropine. Both vasoactive intestinal polypeptide and gastrin-releasing peptide stimulated PSP secretion. PSP concentration in the juice decreased in response to secretin and increased after cholecystokinin octapeptide (CCK-8), but both increased PSP output. In conscious pigs, pancreatic secretion of protein and PSP increased in parallel. Like pancreatic enzyme secretion, we conclude that PSP secretion is controlled by parasympathetic mechanisms that include both cholinergic and peptidergic pathways and by endocrine mechanisms that may include both secretin and CCK-8. PMID- 8430802 TI - Interleukin-1 beta modulation of norepinephrine release from rat myenteric nerves. AB - We examined the ability of human recombinant interleukin-1 beta (hrIL-1 beta) to alter the release of [3H]norepinephrine ([3H]NE) by KCl or electrical field stimulation in longitudinal muscle-myenteric plexus of rat intestine. The cytokine had no immediate effect on either the basal or evoked release of [3H]NE. However, hrIL-1 beta caused a biphasic time-dependent suppression of evoked [3H]NE release that was delayed in onset. IL-1 beta also stimulated the cycloheximide-sensitive uptake of [35S] methionine uptake by the tissue. The initial suppression of [3H]NE release was observed after 30 min and could not be inhibited by cycloheximide. A delayed peak was observed after 120 min and was inhibited by cycloheximide. The effect of IL-1 beta was maximal at 10 ng/ml and could be prevented by a neutralizing anti-IL-1 beta antibody or by preincubating the tissue with an IL-1-receptor antagonist. These results indicate that IL-1 beta suppresses [3H]NE release from rat myenteric plexus by two mechanisms, one of which is independent of protein synthesis and the other of which is mediated by endogenous IL-1. PMID- 8430803 TI - Na(+)-independent multispecific anion transporter mediates active transport of pravastatin into rat liver. AB - To examine whether the relatively selective inhibition of hepatic cholesterol synthesis by the hydrophilic 3-hydroxyl-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor pravastatin in vivo may be due to the existence of a specific uptake mechanism in the liver, the uptake by isolated rat hepatocytes was investigated. The uptake was composed of a saturable component [Michaelis constant (Km) 29 microM, maximal uptake rate 546 pmol.min-1.mg-1] and nonspecific diffusion (nonspecific uptake clearance 1.6 microliters.min-1.mg-1), inhibited by hypothermia, metabolic inhibitors, sulfhydryl-modifying reagents, and inhibitor of anion exchanger, whereas replacement of Na+ by choline+ or Cl- by gluconate- did not alter the uptake. Competitive inhibition was observed by a more highly lipophilic HMG-CoA reductase inhibitor simvastatin (open acid form), dibromosulfophthalein, cholate, and taurocholate. Pravastatin inhibited Na(+) independent taurocholate uptake with an inhibition constant comparable with the Km value of pravastatin itself. Furthermore, the hepatic permeability clearance in vivo obtained with intact rats was comparable with that in vitro, indicating that the carrier-mediated active transport system we demonstrated in vitro is responsible for the hepatic uptake in vivo. These findings demonstrated that the hepatic uptake of pravastatin occurs via a carrier-mediated active transport mechanism utilizing the so-called multispecific anion transporter, which is common with the Na(+)-independent bile acid uptake system, and that this is one of the mechanisms for its selective inhibition of hepatic cholesterol synthesis in vivo. PMID- 8430804 TI - Preepithelial mucus-HCO-3 layer protects against intracellular acidosis in acid exposed gastric mucosa. AB - The role of the preepithelial mucus-HCO-3 layer in protection against intracellular acidosis was investigated in isolated Necturus gastric antral mucosa exposed to luminal acid by simultaneous measurement of intracellular pH (pH(i)) and extracellular surface pH (pHs) in surface epithelium with microelectrode technique. Acidification of the luminal perfusate to pH 2.5 acidified pH(i) in surface epithelial cells from 7.33 +/- 0.02 to 7.20 +/- 0.04, whereas pHs fell from 6.75 +/- 0.21 to 5.20 +/- 0.25 (P < 0.01; n = 9), followed by a steady state for at least 2 h. Inhibition of epithelial HCO-3 secretion and transport by removal of serosal HCO-3 and CO2 (HEPES and O2 substitution) during acid exposure provoked a progressive acidification of pHs from 5.60 +/- 0.41 to 2.74 +/- 0.14 in 30 min (P < 0.01; n = 9), which was accompanied, after a 5- to 10-min delay, by acidification of pH(i) from 7.21 +/- 0.03 to 5.68 +/- 0.26 (P < 0.01). Digestion of the surface mucus gel by pepsin (5% wt/vol) at pH 2.5 caused a slow acidification of pHs from 5.22 +/- 0.59 to 3.60 +/- 0.46 within 2 h. This was followed by a more rapid acidification to 2.53 +/- 0.38 (P < 0.01; n = 7), with concomitant acidification of pH(i) from 7.19 +/- 0.05 to 6.03 +/- 0.33 (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430805 TI - Selective accumulation of methylene blue by interstitial cells of Cajal in canine colon. AB - The network of interstitial cells of Cajal (ICC) at the submucosal surface of the canine colon was selectively stained by incubation with 15-50 microM methylene blue for 30-45 min. The network was composed of regularly scattered ICC cell bodies interconnected by long processes. Circular muscle cells were unstained. Staining of neurons was limited to one or two axons within bundles. The ICC network had a thickness of a single cell, since no overlapping of ICC cell bodies was observed. The ICC network connected the circular muscle cells at the submucosal surface across the septa which circumferentially divided the circular muscle into lamellae. Methylene blue at 50 microM slightly decreased the resting membrane potential and increased the duration of slow waves, leading to an increase in the force of phasic contractions, with no significant influence on other slow-wave parameters. Methylene blue produced neither electrophysiological nor mechanical effects on circular muscle preparations from which the submuscular ICC network was removed, indicating that the excitatory effects of methylene blue on the full-thickness circular muscle layer were mediated by ICC. In summary, the three-dimensional aspects of the submuscular ICC network can be visualized after selective staining by methylene blue. This staining does not affect physiological characteristics of smooth muscle cells. PMID- 8430806 TI - Release of nitric oxide by activation of nonadrenergic noncholinergic neurons of internal anal sphincter. AB - The purpose of the present study was to investigate the direct release of nitric oxide (NO) in response to the stimulation of nonadrenergic noncholinergic (NANC) nerves. The studies were performed on isolated smooth muscle strips of the opossum (Didelphis virginiana) internal anal sphincter (IAS). Electrical field stimulation (EFS) using the appropriate parameters caused a frequency-dependent fall in the resting tone of the IAS. The release of NO was measured directly by the chemiluminescence method. The stimulation of NANC neurons by EFS and the nicotinic stimulant 1,1-dimethyl-4-phenylpiperazinium (DMPP) caused IAS relaxation with an accompanying release of NO. The release of NO and the fall in the resting tension of IAS in response to lower frequencies of EFS and DMPP were abolished by pretreatment of the smooth muscles with the neurotoxin tetrodotoxin and the NO-synthase inhibitor NG-nitro-L-arginine (L-NNA). The obliteration of the release of NO and the IAS relaxation in the presence of L-NNA reversed to control levels by the addition of the NO precursor L-arginine. The effect of L NNA and L-arginine on NO release and IAS relaxation was stereoselective, since D NNA and D-arginine had no significant effect. Vasoactive intestinal polypeptide also caused release of NO from IAS smooth muscle strips, which was abolished by L NNA. However, isoproterenol and atrial natriuretic factor caused IAS relaxation without any increase in NO release. In conclusion, these studies demonstrate the direct release of NO in response to the stimulation of NANC inhibitory neurons of the gut. PMID- 8430807 TI - Histamine receptors on submucous neurons in guinea pig colon. AB - Intracellular microelectrodes were used to investigate the actions of histamine in the submucous plexus of the distal colon of the guinea pig. Three effects resulted from application of histamine to submucous neurons. The first was membrane depolarization associated with increased input resistance and augmented excitability. The second was presynaptic suppression of acetylcholine release at nicotinic synapses. The third occurred during long-term application and consisted of recurrent trains of action potentials associated with periodic depolarization of membrane potential. Pharmacological analysis, with selective agonists and antagonists, suggested mediation of the first and third response by postsynaptic histamine H2 receptors. The second response was mediated by presynaptic histamine H3 receptors. These actions of histamine represent a mechanism for neuroimmune signaling between mucosal mast cells and submucous neurons in gastrointestinal type 1 hypersensitivity reactions to allergens. PMID- 8430808 TI - Pharmacological basis of contractile effects of peptidoleukotrienes on rabbit colonic muscularis mucosae. AB - The present study was designed to determine the mechanism(s) underlying the excitatory effects of several sulfidopeptide leukotrienes (LTs) on the muscularis mucosae in three regions of the rabbit colon. Proximal colonic muscularis mucosae was refractory to LTs C4, D4, and E4. In addition, it exhibited no responses to prostaglandin (PG) E2 and only a minimal contractile response to PGF2 alpha. Mid and distal colonic muscularis mucosae each responded to LTs C4, D4, and E4 and PGs E2 and F2 alpha with concentration-dependent contractions. In both regions, responses to LTD4 and LTE4 were abolished by indomethacin (10(-6) M) pretreatment. LTC4-induced responses were reduced approximately 50% by this procedure. The residual contraction to LTC4 was resistant to both tetrodotoxin (10(-6) M) and atropine (10(-6) M). In separate experiments, responses to LTC4 were also reduced by approximately 50% if LTC4 conversion to LTD4 and LTE4 was first prevented by L-serine borate (45 mM) in combination with L-cysteine (10 mM). It is concluded that proximal colonic muscularis mucosae lacks the appropriate functional excitatory LT and PG receptors. On mid and distal colonic muscularis mucosae, the actions of LTD4 and LTE4 and, in part, LTC4 are the result of PG production, whereas LTC4 has an additional direct action, possibly mediated through a selective LTC4 receptor. PMID- 8430809 TI - Cholera toxin-sensitive neurons in guinea pig submucosal plexus. AB - Cholera toxin (CT) increases intestinal secretions by direct stimulation of mucosal enterocytes; enteric neurons also may play a role. We tested the latter possibility by retrograde labeling of mucosal terminals in guinea pig small intestine with the B subunit of CT (B-CT) and by intracellular recordings from submucosal neurons during superfusion with CT. All vasoactive intestinal peptide (VIP)-positive neurons, and only VIP-positive neurons, were labeled with B-CT. Fluorogold (FG) was used to retrogradely label nerve terminals in submucosal arterioles in preparations in which B-CT labeled mucosal terminals; colocalization of B-CT with FG was observed in neurons up to 3 mm from the site of FG application. CT selectively depolarized neurons known to contain VIP. We conclude that all VIP-containing neurons, and only VIP neurons, in guinea pig submucosal plexus possess B-CT binding sites and can be activated by CT. Some of these neurons provide a dual innervation to both arterioles and mucosa. We suggest that one functional consequence of CT may be to activate vasodilator nerves, thus increasing vascular perfusion of the mucosa to further stimulate intestinal secretions. PMID- 8430810 TI - Activation of activating protein 1 during hepatic acute phase response. AB - During an acute phase response following inflammatory stimuli, specific changes occur in the synthesis and secretion of many hepatic proteins. Because the expression of differentiated function requires the coordinated regulation of many genes, we investigated the activity of general and tissue-specific transcription factors using a rat liver model of the acute phase response induced by Freund's adjuvant. Nuclear extracts and RNAs were prepared throughout a 48-h posttreatment period. Mobility shift assays revealed increased binding activity by nuclear factor-kappa B, interleukin-6 (IL-6) responsive element binding protein, and activating protein 1 (AP-1). Two AP-1 complexes were induced during the acute phase response, and correlation between their presence and transcription activity was demonstrated by transfection studies. Elevated binding activity of AP-1 also correlated with elevated levels of c-jun, junD, junB, and c-fos mRNAs. Western blots showed elevated hepatic levels of c-Jun but not c-Fos proteins during the acute phase response. In addition, IL-6, tumor necrosis factor-alpha, and IL-1 beta, cytokine regulators of the acute phase response, stimulated expression of an AP-1 responsive reporter gene introduced by DNA-mediated transfection into adult rat hepatocytes in primary culture. These findings demonstrate the complexity of AP-1 hepatic transcription factor responses to humoral regulators with direct hepatocellular effects. PMID- 8430811 TI - Smooth muscle guanine nucleotides and receptor-effector coupling following inhibition of oxidative energy production. AB - We measured total concentrations of guanosine triphosphate (GTP) and guanosine diphosphate (GDP) in rabbit aortic smooth muscle under several different conditions. We computed free [GDP] and free GTP/GDP (using a Keq of 1.0 for the nucleoside diphosphate kinase reduction) under these conditions. At a time when muscle was contracted by 15 microM norepinephrine (NE) for 5 min under normoxia, [GTP], free [GDP], and free GTP/GDP were 0.29 +/- 0.03 mM, 3.5 microM, and 82, respectively. Following rapid inhibition of oxidative energy production during NE evoked maintained force, which is associated with slow decreases in mean tissue [PCr], and [ATP] and force relaxation, [GTP] and free GTP/GDP were decreased at relaxation threshold to 0.22 +/- 0.02 (SE) mM and 43, respectively, and progressively fell further, paralleling decreases in force and [ATP] and [PCr]. There were marked decreases in the sum of GTP + GDP contents under conditions where muscle energy stores were decreased (i.e., low [PCr] + [ATP]). Similar data were obtained during a 50 mM KCl-evoked contracture. Free [GDP] increased from normoxic values of 3.5 microM to values as great as 6.0 microM at low energy store states. Free GDP was equivalent to 6% of total GDP under normoxia and increased to 16-21% of total GDP under conditions of low energy stores. Evidence was obtained that decreases in [GTP] or free GTP/GDP seen under conditions of low total energy stores were not sufficient to inhibit heterotrimeric G protein function and uncouple receptor-effector coupling. PMID- 8430812 TI - Susceptibility to ozone-induced inflammation. I. Genetic control of the response to subacute exposure. AB - We demonstrated previously that C57BL/6J (B6) inbred mice are susceptible and C3H/HeJ (C3) mice are resistant to airway inflammation that is induced by acute (3 h) exposure to 2 parts per million (ppm) ozone (O3). In the present study we tested the hypothesis that B6 and C3 mice are also differentially susceptible to the airway inflammatory responses to subacute (72 h) exposure to environmentally relevant concentrations of O3 (0.12 and 0.30 ppm). Male mice (20-25 g, 5-7 wk) were exposed continuously to 0.12 ppm O3, 0.30 ppm O3, or filtered air (control). Pulmonary inflammation was assessed after 24, 48, and 72 h by differential cell count and total protein in bronchoalveolar lavage (BAL) returns. Exposure to 0.12 ppm O3 caused significant influx of alveolar macrophages, polymorphonuclear leukocytes (PMNs), lymphocytes, and total BAL protein in both strains, but no differences in the magnitude of the responses were found between B6 and C3 mice. In contrast to the effect of 0.12 ppm O3, exposure to 0.30 ppm O3 elicited significantly greater numbers of inflammatory cells and BAL protein concentration in B6 mice relative to C3 mice. The phenotypes of the B6 and C3 mice were termed susceptible and resistant, respectively. To further evaluate the potential genetic contribution to the inflammatory response to 0.30 ppm O3, the F1, F2, and backcross progeny from B6 and C3 progenitors were examined. The ratios of susceptible and resistant phenotypes of these progeny support the hypothesis that a single autosomal recessive gene confers susceptibility to subacute O3-induced inflammation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430813 TI - Susceptibility to ozone-induced inflammation. II. Separate loci control responses to acute and subacute exposures. AB - We demonstrated previously that inbred strains of mice are differentially susceptible to acute (3 h) and subacute (48 h) exposures to 2 parts per million (ppm) ozone (O3) and 0.30 ppm O3, respectively. Genetic studies with O3-resistant C3H/HeJ and O3-susceptible C57BL/6J strains have indicated that susceptibility to each of these O3 exposures is under Mendelian (single gene) control. In the present study, we hypothesized that the same gene controls susceptibility to the airway inflammatory responses to 2 ppm and 0.30 ppm O3 exposures. To test this hypothesis, airway inflammation was induced in 10 BXH and 16 BXD recombinant inbred (RI) strains of mice by acute as well as subacute O3 exposures. Airway inflammation was assessed by counting the number of polymorphonuclear leukocytes (PMNs) in bronchoalveolar lavage (BAL) returns obtained immediately after 48-h subacute exposure to 0.30 ppm O3, or 6 h after 3 h acute exposure to 2 ppm O3. Each RI strain was classified as susceptible or resistant to each exposure, based on a comparison of mean numbers of PMNs with those of the respective progenitor strains. For each RI set, a phenotypic strain distribution pattern (SDP) was thus derived for each exposure regimen, and the SDPs were then compared for concordance. Among the BXH RI strains, 4 of 10 responded discordantly to the two exposures: 3 were susceptible to acute exposure and resistant to subacute exposure, whereas 1 was conversely susceptible. Among the BXD RI strains, 4 of 16 were discordant: 1 was susceptible to acute exposure, and resistant to subacute exposure, whereas 3 were conversely susceptible.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430814 TI - Trafficking of surfactant protein A in fetal rabbit lung in organ culture. AB - Surfactant protein A (SP-A), a major protein component of pulmonary surfactant, is a developmentally and hormonally regulated sialoglycoprotein expressed in type II pneumonocytes. Surfactant proteins and glycerophospholipids are transported to multilamellar structures termed lamellar bodies, which serve to store surfactant lipoprotein until secretion by exocytosis into the alveolar lumen. The cellular mechanism(s) for targeting of SP-A and other surfactant components to lamellar bodies is unknown. In the present study, we have investigated the transport of SP A to lamellar bodies in fetal rabbit lung tissue in organ culture using pulse chase analysis of [35S]-methionine-labeled SP-A protein. SP-A accumulated in lamellar bodies within 1-3 h of synthesis; lamellar body SP-A was found to be endoglycosidase H resistant and represented 30-40% of the radiolabeled SP-A recovered from the tissue for periods of up to 12 h postlabeling. Based on our estimates of lamellar body recovery from tissue homogenates, lamellar body associated SP-A may account for 60-80% of the SP-A present in the fetal lung explants. Treatment of fetal rabbit lung explants with inhibitors of oligosaccharide addition (tunicamycin) and processing (castanospermine), which act within the endoplasmic reticulum, significantly reduced the rate of transport of newly synthesized SP-A to lamellar bodies. An inhibitor of oligosaccharide processing that acts on a processing step that takes place within the Golgi apparatus (swainsonine) reduced the rate of transport of radiolabeled SP-A to lamellar bodies by approximately 50%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430815 TI - Differences in Ca2+ mobilization by muscarinic agonists in tracheal smooth muscle. AB - The muscarinic agonists acetylcholine (ACh) and McN-A-343 activate a homogeneous population of M3 receptors in canine tracheal smooth muscle. However, ACh is much more efficacious than McN-A-343 both at stimulating force development and active shortening and at antagonizing relaxation induced by isoproterenol. In other tissues, the same muscarinic receptor may be coupled to multiple subcellular pathways, but activate different pathways depending on the efficacy of the agonist. The present study investigated mechanisms of excitation-contraction coupling in canine tracheal smooth muscle by muscarinic agonists of different efficacy. ACh was more effective at stimulating inositol phosphate production and elicited a large initial transient increase in intracellular Ca2+ concentration ([Ca2+]i), whereas McN-A-343 elicited only a slow gradual rise in [Ca2+]i. Extracellular Ca2+ influx through voltage-operated channels played a minor role in contractions induced by either agonist. Results suggest that contractions by ACh and McN-A-343 may be mediated by the same subcellular pathways; however, the greater potency of ACh at stimulating those pathways results in very different kinetics of Ca2+ activation. PMID- 8430816 TI - Growth of immature lung transplanted into an adult recipient. AB - Syngeneic (Lewis-to-Lewis) and allogeneic (Brown Norway-to-Lewis) unilateral left lung transplants were performed between immature rats aged 6 wk (donors) and adult animals aged 4 mo (recipients). Transplanted animals were killed either 2 wk or 6 mo after operation. Right and left lungs were analyzed separately by quantitative light microscopic techniques, and findings were compared with control animals matched for age and strain. The immature transplanted left lung continued to grow to achieve its predicted adult number of alveoli. Six months after transplantation the alveoli and airways were larger than controls in allogeneic animals (P < 0.001) but were of normal size in syngeneic animals. After both syngeneic and allogeneic transplantation the recipient contralateral mature native right lung showed an increase in volume after 6 mo (P < 0.001), abnormal in a mature lung, due to an increase in size (P < 0.01 in allogeneic, P < 0.05 in syngeneic) and alveolar number (P < 0.02 in both). This study indicates that in rats, transplanted immature lungs can fulfill their growth potential even when transplanted into mature recipients. PMID- 8430817 TI - ED1-containing cellular fibronectin release into lung lymph during lung vascular injury with postoperative bacteremia. AB - Fibronectin (Fn) exists in both a soluble and insoluble form. Soluble Fn in plasma and lymph is an opsonic molecule that enhances phagocytic host defense. Insoluble Fn in the subendothelial and extracellular matrix is an adhesive molecule that mediates cell adhesion to substratum. The extracellular matrix of tissues such as the lung contains a mixture of both plasma-derived fibronectin (pFn) as well as locally synthesized cellular fibronectin (cFn). cFn is antigenically related to pFn, but cFn has extra domains (ED1 and ED2) that do not exist in liver synthesized pFn. The purpose of this study was to determine whether ED1-Fn was released into lung lymph before an increase in lung vascular permeability following postoperative bacteremia. Male sheep (n = 8) with surgically prepared lung lymph fistulae were infused intravenously with a sublethal dose (5 x 10(8)) of Pseudomonas aeruginosa 2 days following surgery. Lymph flow (QL), lymph-to-plasma (L/P) total protein ratio, lung protein clearance (QL x L/P), and hemodynamics were measured over 48 h following bacterial challenge. The lymph and plasma ED1-Fn concentrations were determined by enzyme-linked immunosorbent assay (ELISA) using a murine monoclonal antibody specific to the ED1 region of human cFn. There was a rapid rise of ED1-Fn flux in lung lymph which was evident 60 min after the start of bacterial infusion, resulting in a maximum three- to fourfold increase (P < 0.05) in this parameter. In contrast, the ED1-Fn concentration in plasma before bacterial infusion was less than lung lymph and it did not increase over the initial 6 h following bacterial infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430818 TI - Tumor necrosis factor-alpha activates pulmonary artery endothelial protein kinase C. AB - We investigated the hypothesis that tumor necrosis factor-alpha (TNF) activates pulmonary endothelial protein kinase C (PKC). Confluent bovine pulmonary artery endothelial monolayers were exposed to recombinant human TNF, and the translocation of PKC, an indicator of enzyme activation, was studied using both slot immunoblotting and immunofluorescence. For slot immunoblot analysis, membrane and cytosol lysate fractions were prepared, and PKC antigen was assessed using MC5 monoclonal anti-PKC antibody. TNF (1,000 U/ml for 15 min) induced translocation of PKC into the membrane. Immunofluorescence analysis with the MC5 antibody was also used. Monolayers treated with culture medium showed diffuse cytoplasmic fluorescence. In contrast, treatment with either TNF (1,000 U/ml for 15 min) or 1,2-dioctanoylglycerol (4 x 10(-5) M for 5 min), a diacylglycerol that activates PKC, resulted in translocation of fluorescence to the cell periphery; fine, punctate PKC-associated fluorescence was localized to the margins of cells. The TNF-induced translocation of PKC was inhibited using either IP-300 polyclonal anti-TNF antibody (indicating that the TNF effect was not due to the vehicle or contaminating endotoxin) or calphostin C (10(-6) M for 15 min), which inhibits PKC activation by interacting with the regulatory diacylglycerol-binding domain. TNF treatment had no effect on either the content of PKC, or of total protein, in the membrane + cytosol, and cycloheximide (40 microM for 5 min) did not alter the translocation of PKC induced by TNF; these results indicate that the effect of TNF on PKC translocation was related to neither de novo membrane synthesis of PKC (as opposed to translocation per se) nor nonspecific augmentation of protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430819 TI - Protein synthesis in pulmonary arteries from rats exposed to hyperoxia. AB - These studies were undertaken to determine the relationship of early changes in the synthesis rates and contents of collagen, elastin, and soluble tissue protein of pulmonary arteries in rats exposed chronically to normobaric hyperoxia. The growth response of pulmonary arteries was characterized by proportionate increases in the contents of the three protein fractions after 7 days (130% of control) and 21 days (194% of control) of exposure. Fractional rates of protein synthesis were assessed both in vivo and in vitro with the use of several radiolabeled amino acids as tracers to minimize uncertainties of the relationships of the specific radioactivities of measured amino acid pools and the precursors for the proteins fractions. Values for fractional synthesis rates of collagen, elastin, and soluble protein in vitro in pulmonary arteries isolated from control rats were 2.2, 1.6, and 19%/day, respectively. Rates of synthesis of collagen and soluble protein in vitro were approximately 20% lower than that determined in control rats in vivo. The fractional synthesis rates of the three protein fractions in isolated arteries from experimental rats were unchanged after 1 day of hyperoxic exposure, decreased marginally after 3 days, and markedly increased after 7 days. At this time the absolute increments in the fractional synthesis rates of collagen (+4.7%/day) and elastin (+5.0%/day) were less than that of soluble tissue protein (+16%/day) and were more comparable to the accumulation rate of proteins in the tissue. The disproportionate increment in the fractional rate of soluble protein synthesis suggests that the fractional rate of degradation of soluble protein was also increased during the growth response in this model of hypertension. PMID- 8430820 TI - Integrin receptors in renal tubular epithelium: new insights into pathophysiology of acute renal failure. AB - This review summarizes the existing evidence implicating disordered adhesion of renal tubular epithelial cells to the basement membrane in the pathophysiology of acute renal failure. The following three major lines of investigation are discussed: 1) exfoliation of renal tubular epithelial cells as a potential mechanism of tubular obstruction, 2) normal distribution of integrin receptors along the tubular apparatus, and 3) redistribution of integrin receptors and remodeling of the cytoskeleton following acute injury to renal tubular epithelium. We advance the hypothesis that the loss of the basolateral expression of integrin receptors is responsible for the exfoliation of viable proximal epithelial cells and that the redistribution of integrin receptors from the basolateral to the apical surface of epithelial cells facilitates adhesion of detached cells to the in situ cells. These two processes culminate in tubular obstruction. PMID- 8430821 TI - Streptozotocin-induced renal hemodynamic changes in isogenic Lewis rats: a kidney transplant study. AB - Streptozotocin (STZ)-induced diabetes mellitus is associated with decreased renal clearances of inulin and p-aminohippurate (PAH). The present experiments were designed to determine whether STZ-induced renal hemodynamic changes are due to the drug per se, rather than to the diabetic state that it induces. Isogenic Lewis rats with native right and transplanted left kidneys were studied. In one group, kidney donors received 50 mg STZ/kg body wt on day 1 and transplantation was performed on day 4 (untreated recipients). On day 29, the inulin and PAH clearances of these nondiabetic recipients were, respectively, 0.94 +/- 0.04 and 2.58 +/- 0.11 ml.min-1 x g-1 for the transplanted left kidney (previously exposed to STZ) and 0.95 +/- 0.07 and 2.54 +/- 0.14 ml.min-1 x g-1 for the native right kidney (never exposed to STZ). In another group, recipients received STZ on day 1 and transplantation was performed on day 4 (untreated donors). On day 29, the inulin and PAH clearances of these diabetic recipients were, respectively, 0.62 +/- 0.04 and 1.46 +/- 0.11 ml.min-1 x g-1 for the transplanted left kidney (never exposed to STZ) and 0.61 +/- 0.05 and 1.42 +/- 0.08 ml.min-1 x g-1 for the native right kidney (previously exposed to STZ). We conclude that the diabetic state, rather than STZ, is responsible for the decreased renal clearances of inulin and PAH in this experimental model. PMID- 8430822 TI - Fibronectin metabolism by human mesangial cells: effects of collagens. AB - In the present study we assessed whether the fibronectin (FN) metabolism of human mesangial cells (HMC) in culture is influenced by the contact of HMC with collagens type I and IV. HMC were grown on collagen gels or on collagen-coated surfaces (collagen films). FN concentrations were measured by enzyme-linked immunosorbent assay; FN synthesis was measured by metabolic labeling and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In addition, the structure of matrix FN was examined by immunofluorescence microscopy. Compared with cells grown on plastic, HMC on collagen gels or collagen films accumulated greater amounts of FN in the cell matrix, and in these cultures, matrix FN was organized into a complex mesh of fibers. FN fiber formation was more prominent in cells adherent to collagen IV than in cells adherent to collagen I, and these fibers were observed as early as day 1 in culture. HMC adherent to plastic deposited matrix FN as patches and only occasionally as FN fibers localized to the periphery of the cell. The accumulation of FN in the matrix of HMC on collagen was not due to an increased rate of FN synthesis. In fact, HMC on collagen gels synthesized less FN than HMC on plastic. The present results indicate that the accumulation of FN in the matrix of HMC on collagen is due to the fact that this FN is less likely to be released into the supernatant than the matrix FN produced by HMC on plastic. The decreased FN synthesis demonstrated by HMC on collagen gels was associated with an overall decrease in protein synthesis but was not associated with a decrease in FN mRNA levels. Finally, FN isolated from HMC on collagen gels contained a unique 90-kDa gelatin-binding FN fragment. In conclusion, collagens have effects on the synthesis, localization, organization, and catabolism of FN produced by HMC in culture. In particular, collagen IV, the collagen normally present in the glomerular mesangium, appears to influence uniquely the organization of mesangial matrix FN. PMID- 8430823 TI - KCl and angiotensin responses in isolated rat renal arterioles: effects of diltiazem and low-calcium medium. AB - Studies in intact renovascular models have shown that calcium entry blockers inhibit angiotensin (ANG II)-induced vasoconstriction in afferent (AA) but not efferent arterioles (EA), suggesting that increases in smooth muscle cell cytosolic calcium, the initiating intracellular message, result from entry through potential-operated channels in AA, but from organelle storage mobilization or entry through nonpotential-operated channels in EA. The present study examined the effects of diltiazem (10(-5) M) on the constrictor responses to KCl (50 mM) and half-maximal constricting concentrations (EC50) of ANG II and the effects of low-calcium bathing medium on EC50 ANG II responses in isolated rat AA and EA. KCl caused slightly greater decreases in lumen diameter in AA than in EA (P < 0.05) that were completely inhibited by diltiazem in both. Vasoconstriction to ANG II was significantly inhibited by diltiazem (29 +/- 12 vs. 67 +/- 31%; P < 0.02) in AA. However, constrictor response to ANG II in EA was unchanged by diltiazem (42 +/- 32 vs. 41 +/- 31%). Constriction to ANG II of AA in low-calcium medium was significantly attenuated (8 +/- 13 vs. 54 +/- 12%; P < 0.01); however, EA constrictor response was not affected (43 +/- 22 vs. 51 +/- 19%). These data indicate that EC50 ANG II-induced AA constriction requires calcium entry primarily through potential-operated channels. While potential operated calcium entry channels can be functionally expressed in EA, intracellular calcium mobilization is the primary mechanism for ANG II-induced constriction. PMID- 8430824 TI - Immunocytochemical characterization of the high-affinity thiazide diuretic receptor in rabbit renal cortex. AB - Thiazide diuretics increase urinary NaCl excretion primarily by inhibiting Na and Cl transport across the apical membrane of cells in the renal distal tubule. Although these diuretics bind to a membrane protein that couples transport of Na and Cl directly, the molecular nature of this transporter and its localization in the mammalian kidney remain controversial. The present experiments were designed to develop monoclonal antibodies to the high-affinity thiazide diuretic receptor to investigate its molecular characteristics and its cellular and subcellular localization in rabbit kidney. Mice were immunized with high-affinity thiazide diuretic receptors that had been partially purified from rabbit kidney cortex. Resulting hybridomas were screened for the ability to immunoprecipitate thiazide diuretic receptors that were labeled with the thiazide-like diuretic [3H]metolazone. A single hybridoma (MAb JM5) produced antibodies capable of immunoprecipitating up to 80% of the labeled thiazide receptors from solubilized renal cortical membranes. MAb JM5 reacted with a 125-kDa protein on Western blots of solubilized renal cortical apical membranes. It stained the apical membrane of cells in the distal convoluted and connecting tubule but did not stain proximal tubules, glomeruli, or interstitial structures. Less intense staining of apical membranes of principal cells in the collecting tubule and a subpopulation of cells in the thick ascending limb were also present. These results indicate that the high-affinity thiazide diuretic receptor comprises a 125-kDa protein that localizes to the apical membrane of cells in the renal distal tubule. PMID- 8430825 TI - Redistribution and dysfunction of integrins in cultured renal epithelial cells exposed to oxidative stress. AB - Tubular obstruction by detached renal tubular epithelial cells is a major cause of oliguria in acute renal failure. Viable renal tubular cells can be recovered from urine of patients with acute tubular necrosis, suggesting a possible defect in cell adhesion to the basement membrane. To study this process of epithelial cell desquamation in vitro, we investigated the effect of nonlethal oxidative stress on the integrin adhesion receptors of the primate kidney epithelial cell line BS-C-1. Morphological and functional studies of cell adhesion properties included the following: interference reflection microscopy, intravital confocal microscopy and immunocytochemistry, flow cytometric analysis of integrin receptor abundance, and cell-matrix attachment assay. High levels of the integrin subunits alpha 3, alpha v, and beta 1 were detected on the cell surface by fluorescence activated cell sorting (FACS) analysis, as well as lower levels of alpha 1, alpha 2, alpha 4, alpha 5, alpha 6, and beta 3. Exposure of BS-C-1 cells to nonlethal oxidative stress resulted in the disruption of focal contacts, disappearance of talin from the basal cell surface, and in the redistribution of integrin alpha 3 subunits from predominantly basal location to the apical cell surface. As measured in a quantitative cell attachment assay, oxidative stress decreased BS-C 1 cell adhesion to type IV collagen, laminin, fibronectin, and vitronectin. Defective adhesion was not associated with a loss of alpha 3-, alpha 4-, or alpha v-integrin subunits from the cell surface.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430826 TI - Role of mesangial cell in glomerular response to volume and angiotensin II. AB - We have examined the physiological role of the mesangial cell in the regulation of glomerular hemodynamics utilizing mesangial cell lysis by the administration of antithymocyte antibody serum (ATS) 24 h before micropuncture evaluation. Plasma volume expansion (PVE) in normal NaCl-depleted rats increased single nephron glomerular filtration rate (SNGFR) by 30% because of increases in single nephron plasma flow (SNPF), whereas glomerular capillary hydrostatic pressure (PG) remained constant. SNGFR did not increase with PVE in NaCl-depleted ATS rats despite increases in SNPF, and PG increased significantly (51 +/- 2 to 67 +/- 3 mmHg) because of afferent arteriolar dilation, whereas efferent resistance remained elevated. Angiotensin II (ANG II) infusion in normal rats decreased SNGFR because of reductions in SNPF and the glomerular ultrafiltration coefficient (LpA), whereas the hydrostatic pressure gradient (delta P) increased. In ATS rats ANG II infusion did not change SNGFR, LpA, or delta P. These in vivo studies suggest that the mesangial cell plays an important role in the regulation of LpA, efferent arteriolar resistance, and the regulation of PG, whereas this cell exerts little effect on the afferent arteriole. PMID- 8430827 TI - Differences in dynamic autoregulation of renal blood flow between SHR and WKY rats. AB - In halothane-anesthetized Wistar-Kyoto (WKY) rats the single-nephron blood flow and the proximal tubule pressure oscillate at a frequency of 35-50 mHz because of the operation of the tubuloglomerular feedback (TGF) mechanism. In spontaneously hypertensive rats (SHR) the oscillations are replaced by chaotic fluctuations. We sought to determine whether this change was associated with a change in the dynamic autoregulation of renal blood flow. In halothane-anesthetized 250- to 320 g SHR and WKY rats, renal blood flow was measured during "white noise" forcing of arterial blood pressure. The frequency response of renal vascular admittance was estimated by the method of autoregressive-moving averages. In the frequency band below 60-70 mHz there was a significant difference in the transfer functions between the two strains of rats. This was due mainly to an increased phase difference, but also to a decreased magnitude of the admittance in SHR at frequencies below 20-30 mHz. Above 70 mHz there was no significant difference in the transfer functions. Because TGF is active in the low frequency band (below approximately 100 mHz), whereas the myogenic mechanism also acts in the higher frequency band, we conclude that the change in the dynamics of TGF leads to a change in the dynamic autoregulation of renal blood flow between SHR and WKY rats. This change results in a more efficient dynamic autoregulation of renal blood flow in the SHR compared with the WKY rats. The functional consequences of this, in terms of the regulation of salt and water excretion, are not presently known. PMID- 8430828 TI - Hypertonicity stimulates transcription of gene for Na(+)-myo-inositol cotransporter in MDCK cells. AB - Myo-inositol is a major compatible osmolyte accumulated in the hypertonic renal medulla and in Madin-Darby canine kidney (MDCK) cells cultured in hypertonic media. Myo-inositol is taken up by MDCK cells on a Na(+)-coupled transporter whose activity increases sixfold 24 h after cells are switched to hypertonic medium. To investigate the mechanism of regulation of the cotransporter by hypertonicity, we used the cDNA encoding the canine Na(+)-myo-inositol cotransporter that we recently cloned to measure the abundance of the mRNA for the cotransporter and its rate of transcription after changes in osmolality. When MDCK cells were switched from isotonic to hypertonic medium, cotransporter mRNA abundance rose 10-fold in 16 h. Transcription of the cotransporter gene also rose and 16 h after the switch reached a peak approximately 15-fold that in isotonic cells. When cells were switched back to isotonic medium, mRNA abundance and transcription of the gene returned to isotonic levels in 8 h and transport rate reached isotonic levels in 48 h. Thus transcription appears to be the primary step in regulation of myo-inositol transport by hypertonicity. PMID- 8430829 TI - Effect of captopril on fluctuations of blood pressure and renal blood flow in rats. AB - Arterial blood pressure and renal blood flow (RBF) fluctuations in rats were studied by autoregressive (AR) and autoregressive-moving average (ARMA) modeling. These estimation procedures provided greater sensitivity and frequency resolution than classic fast Fourier transform (FFT)-based methods and also require shorter observation periods. We estimated the transfer function of RBF autoregulation to test whether inhibition of angiotensin-converting enzyme impairs whole kidney dynamic autoregulation. The transfer function in control animals measured with the ARMA method was similar to transfer functions obtained previously, using FFT methods. Because of better frequency resolution, we also detected an oscillation in RBF at 50 mHz, the same frequency as an oscillation in tubular pressure and glomerular filtration rate that had been attributed to tubuloglomerular feedback (TGF), but that FFT methods had not previously found in whole kidney blood flow. Captopril increased the amplitude of RBF fluctuations and increased the gain of the transfer function at frequencies below 100 mHz, a frequency bandwidth previously associated with TGF. The increased gain indicates that TGF operates less effectively to mediate dynamic autoregulation when angiotensin conversion is inhibited. Gain at frequencies greater than 100 mHz, previously ascribed to the myogenic mechanism, was not affected by captopril. These results show that angiotensin, by modulating TGF, reduces fluctuations of RBF about the mean value. PMID- 8430830 TI - Characterization of neutral endopeptidase in vascular smooth muscle cells of rabbit renal cortex. AB - In addition to biological and clearance receptors for atrial natriuretic factor (ANF), cultured vascular smooth muscle cells (VSMC) from the rabbit renal cortex possess ectoenzymes degrading this hormone. We examined whether neutral endopeptidase (NEP) was implicated in this process. The presence of NEP in VSMC was demonstrated as follows. 1) NEP activity measured from the hydrolysis of a synthetic substrate by intact cells cultured in a medium containing 10% fetal calf serum was 1,609 +/- 65 pmol.min-1 x mg-1 [surface localization of the enzyme was confirmed by low activity (4% of total) in the cytosol; release of NEP activity in the medium was negligible]; 2) a monoclonal antibody directed against rabbit NEP specifically stained VSMC membranes; and 3) mRNA from VSMC hybridized a NEP cDNA probe with a single band as shown by Northern blot analysis. The role of NEP in ANF catabolism was demonstrated by incubating 125I-ANF or unlabeled ANF for increasing periods of time with VSMC in the presence of thiorphan (1-100 microM). Intact hormone estimated by trichloroacetic acid precipitation or radio immunoassay, respectively, increased markedly compared with control in the presence of this specific inhibitor of NEP. NEP activity was stimulated (x1.6) in quiescent VSMC deprived from serum during 3 days. This effect was dose dependent and was not observed with creatine kinase activity measured as control. NEP expression at the cell surface estimated by sorting of immunostained cells was also increased in the absence of serum. Northern blot analysis showed increases in the mRNA band of NEP with increasing periods of serum deprivation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430831 TI - The Os/+ mouse: a genetic animal model of reduced renal mass. AB - The ROP [Ra/+ (ragged), Os/+ (oligosyndactyly), and Pt/+ (pintail)] mouse possessing the gene for oligosyndactylism (Os) was evaluated as a potential genetic animal model of reduced renal mass. Young male ROP mice that were heterozygotes with respect to the Os gene (Os/+) and their normal homozygote litter mates (+/+) were used in the present study. Approximately 50% fewer nephrons were present in the Os/+ mice than in the +/+ mice. Hypertrophic changes were detected in the epithelial cells in proximal convoluted and proximal straight tubules as well as in cortical collecting ducts in the kidneys of the Os/+ mice. Glomerular hypertrophy was also noted in the kidneys of these mice. After unilateral nephrectomy, further hypertrophic changes occurred in both Os/+ and +/+ mice, but the magnitude of compensatory growth was greater in the +/+ mice. From a functional standpoint, the Os/+ mice appeared to be capable of maintaining normal fluid and electrolyte homeostasis, even after unilateral nephrectomy. The findings from the present study indicate that the ROP Os/+ mouse can be a useful animal model to study the effects of reduced renal mass. PMID- 8430832 TI - Renal effects of acute endothelial-derived relaxing factor blockade are not mediated by angiotensin II. AB - The renal responses to acute blockade of the endothelial-derived relaxing factor (EDRF) resemble the renal actions of angiotensin II (ANG II), and the present studies were conducted to establish what role, if any, the endogenous renin angiotensin system plays in mediating the renal response to acute EDRF blockade. These studies were conducted in the conscious chronically catheterized rat. In control experiments we observed that acute blockade of ANG II synthesis with converting-enzyme inhibition (CEI) led to a fall in blood pressure (BP) and a slight renal vasodilation but no significant change in glomerular filtration rate (GFR) or renal plasma flow (RPF). Urine flow and sodium excretion were unchanged by CEI. Use of the nonpeptide ANG II receptor antagonist losartan had no effect on BP, renal vascular resistance (RVR), GFR, or RPF; however, urine flow and sodium excretion did rise significantly. Because of the high specificity of losartan, this suggests that, in the normal conscious rat, endogenous ANG II does not control renal vascular tone but does enhance renal sodium reabsorption. ANG II blockade with either CEI or losartan had little effect on BP and no effect on the renal hemodynamic responses to acute EDRF blockade. The marked natriuretic and diuretic response to acute EDRF blockade persists during concomitant losartan but is abolished by CEI. These studies suggest that in the conscious rat the renal hemodynamic response to EDRF blockade is not mediated by endogenous ANG II. PMID- 8430833 TI - Inhibition of nitric oxide synthesis attenuates pressure-induced natriuretic responses in anesthetized dogs. AB - Inhibition of nitric oxide (NO) synthesis by intrarenal administration of nitro-L arginine (NLA) leads to decreases in urinary sodium excretion (UNaV) in association with the increases in renal vascular resistance (RVR). In the present study, we examined the ability of the kidney to alter its sodium excretion in response to acute changes in renal arterial pressure (RAP) in anesthetized dogs before and during intrarenal infusion of NLA (50 micrograms.kg-1.min-1). NO synthesis inhibition in 11 dogs increased RVR by 32 +/- 4% and decreased renal blood flow (RBF) by 25 +/- 3%, outer cortical blood flow by 25 +/- 6%, urine flow by 37 +/- 14%, UNaV by 71 +/- 5%, and fractional excretion of sodium (FENa) by 71 +/- 4%. Glomerular filtration rate was not significantly changed during NLA infusion. As previously reported, there was suppression of the RBF autoregulation plateau during NO synthesis inhibition. In addition, there was a marked attenuation of urine flow and UNaV responses to reductions in RAP (150 to 75 mmHg), with significant reductions in the slopes of the relationships between RAP vs. UNaV and RAP vs. FENa during NLA infusion. Similar responses were observed in nine other dogs treated with the angiotensin receptor antagonist losartan, indicating that an augmented activity of the renin-angiotensin system is not responsible for attenuation of the slope of the pressure-natriuresis relationship during NLA infusion. These data suggest that NO may participate in the mediation of the pressure-natriuresis response. PMID- 8430834 TI - Immunohistochemical mapping of cellular and subcellular distribution of 5-HT1A receptors in rat and human kidneys. AB - Northern blotting studies have demonstrated mRNA for the serotonin 5-HT1A receptor in human neonatal kidney (B. K. Kobilka, T. Frielle, S. Collins, T. Yang Feng, T. S. Kobilka, U. Francke, R. J. Lefkowitz, and M. G. Caron. Nature Lond. 329: 75-79, 1987). To confirm expression of receptor protein in kidney, we raised antibodies to two peptides derived from the third intracellular loop of the human 5-HT1A receptor. Specific immunoglobulin G (IgG) was purified sequentially on protein A-Sepharose and peptide-Affigel 10 columns. Each IgG was able to: 1) quantitatively immunoprecipitate [3H]8-OH-2-(di-n-propylamino)1,2,3,4 tetrahydronaphthalene ([3H]8-OH-DPAT)-labeled human and rat receptors; 2) immunoblot a new protein in cells transfected with human 5-HT1A receptor DNA; and 3) immunoautoradiographically label areas of rat brain (frontal cortex, hippocampus, and lateral septum) in a highly characteristic pattern similar to that labeled by 125I-Bolton-Hunter-8-methoxy-2-(N-propyl-N-propylamino)Tetralin, a specific 5-HT1A receptor autoradiography ligand. By use of a light microscopic immunoperoxidase labeling technique, incubation of each IgG antibody with sections of rat and human kidney demonstrated an identical pattern of immunoreactivity. Specific labeling of basolateral plasma membranes was detected throughout medullary and cortical thick ascending limbs (TAL), in distal convoluted tubules (DCT), in connecting tubule cells of the connecting tubule, and in principal cells of the initial collecting tubule. There was no labeling in the inner medulla, glomeruli, or blood vessels. The labeling was blocked by preincubation with the corresponding peptide, but not with noncorresponding peptide or carrier protein. There was no labeling with preimmune IgG. Electron microscopic immunoperoxidase labeling confirmed the specific localization of the IgG antibody along the basolateral plasma membrane in all positively staining cells in rat kidney. Radioligand binding studies with the specific 5-HT1A receptor ligand [3H]8-OH-DPAT confirmed the presence of 5-HT1A receptor binding sites in bulk-isolated rat medullary TAL. These studies provide the first evidence that the 5-HT1A receptor is expressed on the basolateral surface of TAL and DCT cells of human and rat kidney. The specific localization to these cells suggests a possible role for the 5-HT1A receptor in the regulation of salt and water transport in mammalian kidney. PMID- 8430835 TI - Glycine protection against hypoxic but not phospholipase A2-induced injury in rat proximal tubules. AB - We studied the effects of glycine (2 mM) on hypoxia-induced changes in phospholipids and fatty acids in isolated rat proximal tubules. In this preparation, 25 min of hypoxia caused cell injury, as reflected by the release of lactate dehydrogenase (LDH) (13.1 +/- 0.8 vs. 43.5 +/- 3.2%; P < 0.01). Hypoxia caused increases in fatty acids and in lysophospholipids. Glycine prevented the hypoxia-induced cell injury (LDH 13.1 +/- 0.8 vs. 11 +/- 0.7%; not significant) but did not attenuate the increases in fatty acids or lysophospholipids. In additional experiments, the effects of glycine on phospholipid changes and cell injury induced by exogenous phospholipase A2 (PLA2) were studied. PLA2 caused dramatic increases in fatty acids and lysophospholipids and mild cell injury; these effects were not influenced by glycine. In contrast, glycine attenuated increases in LDH release induced by exposing the tubules to exogenous arachidonic acid. In conclusion, glycine does not prevent the phospholipid degradation induced by either exogenous PLA2 or hypoxia in isolated proximal tubules and yet affords protection against hypoxia and exogenous arachidonic acid. PMID- 8430837 TI - Atrial contractile performance after cessation of atrial fibrillation. AB - Atrial fibrillation is associated with a fall in cardiac output, and cardioversion to sinus rhythm is frequently attempted. After cardioversion, atrial contractile performance might be depressed. It is, however, unclear whether or not atrial contractile performance is altered following atrial fibrillation periods lasting < 1 wk. Atrial contractile performance after short term paroxysmal atrial fibrillation was examined in seven barbiturate anesthetized, open-chest pigs paced at constant ventricular rate after complete atrioventricular block. Percent left atrial systolic shortening (systolic shortening of left atrial diameter in percent of atrial diameter at onset of atrial contraction, %LASS) increased from 100 to 116.2% (107.7-121.8) (median and 95% confidence interval) immediately after cessation of a fibrillation period of 1 min. A brief phase of atrial hypercontractility (%LASS significantly above control) was also demonstrated after fibrillation periods of 5 and 15 min. A subsequent phase of atrial hypocontractility (%LASS significantly below control) was recorded after atrial fibrillation periods of 5, 15, and 30 min. After the 30 min fibrillation period, atrial hypocontractility was most pronounced and reached a nadir of 86.8% (75.1-93.3). PMID- 8430836 TI - Muscle sympathetic nerve responses to dynamic one-legged exercise: effect of body posture. AB - Previous studies examining muscle sympathetic nerve activity (MSNA) during dynamic exercise have focused on upper extremity exercise. The present study was undertaken to investigate 1) MSNA responses to dynamic one-legged knee extensions (DLE) and 2) the role of the cardiopulmonary baroreflexes in the modulation of MSNA responses to DLE. MSNA was measured during 4 min of DLE at 20 (n = 10) and 30 W (n = 9) and during 3 min of DLE at 40 W (n = 9). DLE was performed in the upright (sitting) position and MSNA was recorded in the contralateral leg (peroneal nerve). DLE elicited significant increases in mean arterial pressure (MAP) and heart rate (HR; P < 0.05). In contrast to previous studies using dynamic arm exercise, MSNA (bursts/min) decreased by 25% (P < 0.05) during the first minute of DLE from resting control and remained suppressed during the remaining 3 min of DLE at 20 and 30 W. During the first minute of DLE at 40 W, MSNA (bursts/min) decreased by 18% (P < 0.05), but returned to control levels during the last minute of exercise. Because dynamic leg exercise in the upright position increases venous return, we postulated that upright DLE might increase cardiac filling pressures and stimulate the cardiopulmonary baroreceptors resulting in suppression of MSNA. To investigate this possibility, we measured MSNA and central venous pressure (CVP) during 4 min of both supine and upright DLE at 30 W. MAP, HR, and CVP increased and MSNA decreased from 30 +/- 3 to 22 +/ 3 bursts/min (mean exercise value; P < 0.05) during upright DLE.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430838 TI - Changes in regional myocardial function and external work in exercising dogs with ischemia. AB - Changes in regional myocardial work of the nonischemic wall and left ventricular (LV) asynchrony of the nonischemic wall during exercise-induced ischemia were examined in seven conscious dogs instrumented with a micromanometer for LV pressure measurement and sonomicrometers for control and ischemic wall thickness and LV external short and long axes. Ischemia was produced during steady-state exercise by a pneumatic constrictor on the left circumflex coronary artery. Time difference between peak thickening of control (anterior) and ischemic (posterior) walls was measured as an index of LV asynchrony. LV pressure-wall thickness loop area of both the control wall (LVP-CW loop) and ischemic wall was calculated as an index of regional myocardial external work. With ischemia during exercise, peak LV pressure decreased by 11%, and time difference of peak thickening in the two walls increased, accompanied by marked deformation of the LVP-CW loop during early relaxation, which was related to protodiastolic thickening of the ischemic wall. Thus, despite a significant increase in percent systolic thickening during exercise, loop area of control wall was not enhanced. These changes of the LVP-CW loop were confirmed by calculation of stress-strain loop areas as an additional index of regional myocardial external work but having true dimensions of work. Stress-strain loop area in the control wall during ischemic exercise showed a similar value to that during control exercise, thereby confirming lack of compensatory increase. Thus, during exercise-induced ischemia, regional myocardial external work in the normal region does not increase despite an increase in systolic wall thickening.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430839 TI - Rapid stimulation of Ins (1,4,5)P3 production in rat aorta by NE: correlation with contractile state. AB - Rapid stimulation of Ins(1,4,5)P3 production in rat aorta by NE: correlation with contractile state. Am. J. Physiol. 264 (Heart Circ. Physiol. 33): H126-H132, 1993.--The isomeric composition of inositol phosphates generated in response to norepinephrine (NE) stimulation and the relationship of inositol phosphate production to release of intracellular Ca2+ as measured by contraction were characterized in rat aorta prelabeled with [3H]inositol. NE stimulated a rapid and transient increase in labeled D-myo-inositol 1,4,5-trisphosphate [Ins (1,4,5)P3] levels. A maximal increase in labeled Ins(1,4,5)P3 occurred within 15 s of stimulation followed by a decline to control levels at 5 min. D-Myo-inositol 1,3,4-trisphosphate [Ins-(1,3,4)P3] and D-myo-inositol 1-monophosphate [Ins(1)P] levels also increased rapidly in response to NE. In contrast to the transient production of Ins(1,4,5)P3, Ins(1,3,4)P3 and Ins(1)P production was maintained in the presence of NE. Half-maximal stimulation of Ins(1,4,5)P3 production and Ca2+ release occurred at 0.3 microM NE, and maximal effects were obtained with 10 microM NE. The concentration-response curve and time course for production of Ins(1,4,5)P3 correlated with the neurotransmitter-induced Ca2+ release from intracellular stores, indicating that the level of Ins(1,4,5)P3 regulated the Ca(2+)-release mechanism. In the continued presence of NE, the intracellular pools did not completely refill with Ca2+ despite the return of Ins-(1,4,5)P3 levels to basal at 5 min. These results demonstrate that NE stimulates a rapid increase in Ins(1,4,5)P3 that correlates with contraction in Ca(2+)-free buffer. The reuptake of Ca2+ into intracellular stores is regulated by a mechanism that may not involve Ins(1,4,5)P3. PMID- 8430840 TI - Small apex-to-base heterogeneity in radius-to-thickness ratio by three dimensional magnetic resonance imaging. AB - Reported large base-to-apex differences in endocardial area ejection fraction may suggest large variability in myocardial function and load. To test ventricular load heterogeneities, we measured the ratio of radius of curvature to wall thickness (R/T), as a stress index reflecting myocardial load. End-diastolic (ED) and end-systolic (ES) magnetic resonance cross-sectional images were obtained in 15 open-chest dogs at 5 levels from base to apex, from which 4 three-dimensional thick disks were generated from adjacent image planes. The average R/T for each disk was calculated by planar and three-dimensional methods, using both midwall and endocardial radii of curvature. R/T was normalized to the apical value to quantify the relative changes in myocardial load. Normalized R/T using the midwall three-dimensional approach was 1.08, 1.11, 1.06, and 1.0 for ED (P = NS) and 1.25, 1.013, 1.08, and 1.0 for ES (P < 0.02), base to apex, respectively, while the other methods yielded higher values. Therefore, R/T calculated by the three-dimensional midwall approach shows only small apex-to base variations at ED (< 11%) and ES (< 25%), which is substantially less than the variability in area ejection fraction (102%). This suggests only small base-to-apex load heterogeneities, in spite of large changes in the area ejection fraction, an index reflecting specific ventricular geometry rather than local myocardial function. PMID- 8430841 TI - Effects of indomethacin on brain blood flow and cerebral metabolism in hypoxic newborn piglets. AB - We tested the hypotheses that in newborn piglets indomethacin (Indo) pretreatment blunts the hyperemic brain blood flow (BF) and alters the cerebral metabolic responses to hypoxia and that these responses are dose dependent. We studied 23 chronically instrumented piglets exposed to graded hypoxia (O2 content: 7.1-0.4 microM O2/ml) after pretreatment with high (5 mg/kg, n = 8)-or low (0.3 mg/kg, n = 6)-dose Indo or placebo (diluent, n = 9). Total and regional brain BF increased significantly with decreasing O2 content values (P < 0.01) in all three groups. However, the rise in the brain BF curves with decreasing O2 content values was significantly (P < 0.05) lower in the high-compared with the low-dose group in all brain regions with the greatest effect in the caudal regions. Furthermore, the BF curves in the placebo-treated animals were similar to the low-dose group. The cerebral metabolic rate of O2 (CMR(O2)) and glucose metabolism were preserved in the three groups over all hypoxic ranges until severe hypoxia (O2 content < or = 1.1 microM O2/ml) was achieved in the high-dose group, when CMR(O2) decreased (P < 0.05), and glucose metabolism increased (P < 0.05). The mean arterial blood pressure in the high-dose group during severe hypoxia was 45 mmHg (P > 0.05). Although coupling of cerebral BF and CMR(O2) was preserved in the three groups, this association was significantly altered with high-dose pretreatment. We conclude that an attenuation in the hypoxia-induced brain perfusion by Indo is dose dependent. Alterations in CMR(O2) and glucose metabolism are observed with high-dose pretreatment during severe hypoxia, and the responses to hypoxia are similar with placebo and low-dose Indo pretreatment. PMID- 8430842 TI - Adenosine protects ischemic and reperfused myocardium by receptor-mediated mechanisms. AB - To evaluate the role of adenosine receptors in the mediation of adenosine-induced protection of the heart during ischemia and reperfusion, isolated rabbit hearts were perfused at constant flow with 1 microM adenosine started before low-flow ischemia followed by reperfusion. Adenosine delayed the time of onset of ischemic contracture [to 28 +/- 19 (SD) min compared with 10 +/- 10 min in control hearts] and decreased the amplitude of ischemic contracture (29 +/- 16 vs. 48 +/- 14 mmHg; P < 0.05 for each compared with controls). This protection was accompanied by an increase in tissue ATP content (1.72 +/- 0.78 vs. 0.96 +/- 0.23 mumol/g; P < 0.05) and stimulation of anaerobic glycolysis (lactate production of 0.78 +/- 0.28 mumol.g-1 x min-1 compared with 0.53 +/- 0.23 mumol.g-1 x min-1; P < 0.05). Functional recovery during reperfusion was enhanced by adenosine (developed pressure 88 +/- 16% compared with 57 +/- 23% of baseline; P < 0.05), and tissue necrosis, assessed by creatine kinase release, was decreased. The potent, nonselective adenosine receptor blocker 8-phenyltheophylline (10 microM) blocked all of the salutary effects of adenosine. Adenosine given only at reperfusion modestly attenuated reperfusion-induced contracture. The results suggest that exogenous adenosine attenuates ischemic injury by receptor-mediated stimulation of anaerobic glycolysis. During reperfusion its protective action is related to vasodilation. PMID- 8430843 TI - Endogenous vasoconstrictor tone in intestine of normal and portal hypertensive rats. AB - The purpose of the present study was to determine the effects of endogenous norepinephrine, vasopressin (AVP), and angiotensin II (ANG II) on normal intestinal microvascular dimensions and to determine whether endogenous vasoconstrictor tone was altered in chronic portal hypertension. The intestine of normal and portal hypertensive rats was prepared for in vivo microscopic observation, and an arteriole (1A, 2A, or 3A) was selected for study. Arteriolar diameter and erythrocyte velocity were continuously monitored and used in the calculation of arteriolar blood flow. Once steady-state conditions were established, specific antagonists to alpha-adrenergic, AVP, or ANG II receptors were applied locally to remove the influences of each of these systems. In normal animals, blockade of alpha-adrenergic receptors produced a 1.3, 1.5, and 14.7% increase in the diameter of 1A, 2A, and 3A, respectively. AVP blockade in normal animals produced an 8.7, 1.6, and 1.5% increase in the diameter of 1A, 2A, and 3A, respectively; ANG II blockade only produced an increase in 3A diameter (5.8%). alpha-Adrenergic blockade produced a smaller increase in portal hypertensive 3A diameter (2.3%) compared with normal rats. AVP and ANG II blockade produced a significantly larger dilation of 3A (AVP, 4.8%) and 1A (ANG II, 3.8%), respectively, compared with control. Plasma AVP and ANG II levels were higher in portal hypertensive (AVP, 9.1 pg/ml; ANG II, 8.6 pg/ml) than in normal rats (AVP, 5.5 pg/ml; ANG II, 6.6 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430844 TI - Effect of norepinephrine on rat basilar artery in vivo. AB - In anesthetized rats, we used a cranial window to examine effects of topical norepinephrine on diameter of the basilar artery in vivo. Topical application of norepinephrine increased the diameter of the basilar artery. NG-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase, inhibited vasodilatation to acetylcholine but did not attenuate dilator responses to norepinephrine. Indomethacin also did not attenuate vasodilatation in response to norepinephrine. Dilatation of the basilar artery to norepinephrine was inhibited by propranolol and the beta 1-antagonist atenolol but not by the beta 2-antagonist butoxamine. Thus dilatation of the basilar artery in response to norepinephrine is produced by activation of beta 1-receptors and is not mediated by endothelium-derived relaxing factor or prostanoids. Glibenclamide, a selective inhibitor of ATP sensitive K+ channels, partially inhibited vasodilatation in response to norepinephrine. Forskolin, a direct activator of adenylate cyclase, also increased the diameter of the basilar artery, and glibenclamide attenuated the dilatation. Thus dilatation of rat basilar artery in response to norepinephrine is mediated, in part, by activation of ATP-sensitive K+ channels, and activation of these K+ channels may be achieved by an adenosine 3',5'-cyclic monophosphate dependent mechanism. PMID- 8430845 TI - Effects of perfusion pressure on intracellular calcium, energetics, and function in perfused rat hearts. AB - Effects of perfusion pressure in a range from 50 to 140 cmH2O on intracellular Ca2+ concentration ([Ca2+]i) were evaluated along with cardiac function, energy metabolism, and left ventricular geometry in a concentration of 2 or 4 mM of extracellular Ca2+ ([Ca2+]o) in isovolumic perfused rat hearts. [Ca2+]i was evaluated with a surface fluorometry technique in hearts loaded with indo-1/AM. The systolic and diastolic values and the amplitude (difference between systolic and diastolic values) of indo-1 fluorescence ratio (an index of [Ca2+]i) were linearly related to perfusion pressure. Changes in the fluorescence ratio were harmonious with rapid changes in left ventricular pressure and stabilized within 30-40 s after changes in perfusion pressure. Developed pressure and O2 consumption were closely, linearly correlated with the fluorescence ratio irrespective of [Ca2+]o. Left ventricular end-diastolic wall thickness, measured by 2-dimensional echocardiography, paralleled perfusion pressure and showed a good correlation with the fluorescence ratio. Diastolic myocardial adenosine 3',5'-cyclic monophosphate significantly decreased only at the lowest perfusion pressure. The ln[phosphocreatine]/[Pi] also changed with altered perfusion pressure. In conclusion, perfusion pressure modulates [Ca2+]i, which in turn regulates myocardial contraction and associated O2 utilization. PMID- 8430846 TI - Modulation of vascular tone in renal microcirculation by erythrocytes: role of EDRF. AB - The effect of erythrocytes (red blood cells, RBC) on vascular tone in the renal microcirculation was examined using the juxtamedullary nephron microvascular preparation perfused in vitro with a physiological salt solution containing 5% albumin. The basal diameters of the arcuate, interlobular, proximal, and distal afferent arterioles averaged 444 +/- 24, 74 +/- 3, 29 +/- 1, and 19 +/- 1 micron, respectively, when perfused with a cell-free solution at a pressure of 80 mmHg. The diameters of the arcuate and interlobular arteries increased by 14 +/- 4 and 13 +/- 4%, respectively, whereas the diameter of the proximal and distal portions of the afferent arterioles decreased by 7 +/- 2% when perfusion pressure was elevated from 80 to 160 mmHg. The addition of RBC to the perfusate reduced the basal diameters of interlobular and afferent arterioles by 11 +/- 4 and 15 +/- 3%, respectively. The maximal vasoconstrictor response was seen after the addition of only 1% RBC to the perfusate. Removal of platelets did not block the vasoconstrictor response to addition of RBC to the perfusate. The role of endothelium-derived relaxing factor (EDRF) in the vasoconstrictor response to RBC was studied by addition of nitric oxide synthase inhibitor, N omega-nitro-L arginine (L-NNA, 100 microM) to the perfusate. L-NNA reduced the basal diameters of interlobular and afferent arterioles by 7 +/- 3 and 9 +/- 3%, respectively, and abolished the vasoconstrictor response to RBC. L-NNA had no effect on the pressure-diameter relationships of the preglomerular vasculature when added to perfusates already containing RBC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430847 TI - Noninvasive quantification of principal strains in normal canine hearts using tagged MRI images in 3-D. AB - Previous studies of myocardial strains have been largely limited to invasive procedures in isolated regions. Utilizing images from tagged magnetic resonance imaging (MRI) in three dimensions (3-D), we noninvasively quantified in vivo endocardial (endo) and epicardial (epi) principal strains (PS) throughout the left ventricle (LV) and tested their uniformity. Seven normal hearts in paced reclosed-chest dogs were studied. Combining long- and short-axis images, 24 myocardial cuboids were tagged at end diastole (ED), imaged at end systole and ED, and reconstructed in 3-D. The cuboids were circumferentially arranged in three parallel approximately 1-cm-thick short-axis slices (8 cuboids/slice). By application of finite strain analysis to each cuboid, the major PS (i.e., magnitude and angle with respect to the circumferential direction of maximal shortening) was calculated for each face. when strains are averaged globally (i.e., using all regions), the average magnitude of endo PS exceeded epi PS approximately twofold: -0.24 +/- 0.07 (SD) vs. -0.11 +/- 0.05 (P < 0.05). On the other hand, the PS angle with respect to the circumferential direction at epi exceeded the angle at endo (P < 0.05) by 33 +/- 36 degrees. Average PS direction at epi, 59 +/- 32 degrees, aligned with the expected fiber direction but was perpendicular to it at endo, 26 +/- 30 degrees. However, significant regional variations were observed from wall to wall and from apex to base. When variations in location were accounted for, the pooled SD for the PS magnitudes dropped to 0.032 and for the direction to only 15 degrees. Furthermore, it was found that the anterior-posterior pair of walls contracted differently (P < 0.05) from the septal-lateral pair of walls. These observations indicate that regional myocardial function is heterogeneous and is location dependent. PMID- 8430848 TI - Postural changes in venous pressure gradients in anesthetized monkeys. AB - We examined the hypothesis that head-up and head-down tilt produce a symmetrical hydrostatic load on the veins. Venous pressure was measured in anesthetized monkeys with a transducer-tipped catheter. Changes in venous pressure gradients during head-up tilt corresponded to changes in hydrostatic load. However, changes in venous pressure gradients during head-down tilt were not symmetrical to those during head-up tilt. During head-down tilt, venous pressure in the superior vena cava rose, venous pressure around the right atrium did not change, and venous pressure in the inferior vena cava on the caudal side of the diaphragm rose considerably. The venous pressure of the inferior vena cava caudal to the renal vein then gradually decreased. The inferior vena cava passes through the central tendon of the diaphragm. Thus, during head-down tilt, the gravitational shift of venous blood is impeded by this anatomic structure, and venous pressure around the hepatic vein increases significantly. These data disproved our hypothesis that head-up and head-down tilt induced symmetrical but opposite influences on vena caval pressures. PMID- 8430849 TI - Role of tachycardia and V wave wall stress in the release of ANF during volume loading. AB - Heart rate is believed to be a primary determinant of atrial natriuretic factor (ANF) release; however, we postulated that V wave wall stress is the main signal for ANF release during volume loading. Conscious dogs were volume loaded with 1,000 ml of saline while the heart rate was allowed to vary and on another day while the heart was paced at 240 beats/min. During volume loading, plasma ANF increased from 58 +/- 10 to 221 +/- 31 pg/ml (P < 0.05), and heart rate increased from 97 +/- 3 to 182 +/- 9 beats/min. During pacing, plasma ANF increased from 42 +/- 8 to 85 +/- 10 pg/ml. A wave atrial pressures were increased during pacing and were fixed due to contraction against a closed atrioventricular valve. Volume loading increased plasma ANF to 180 +/- 25 pg/ml. V wave atrial pressure increased markedly, and V wave atrial wall stress increased from 25 +/- 10 to 131 +/- 44 and from 7 +/- 4 to 116 +/- 25 g/cm2, respectively. A wave pressure and wall stress were not increased by volume loading. V wave wall stress and ANF were significantly correlated. V wave atrial wall stress accounts for the majority of change in plasma ANF (60%), while tachycardia and A wave wall stress account for a smaller fraction (40%) of change. PMID- 8430850 TI - Effects of halothane, enflurane, and isoflurane on skinned rat myocardium activated by Ca2+. AB - The effects of halothane (1.9 mM, 9.4 mM), enflurane (3.3 mM, 16.5 mM), and isoflurane (1.6 mM, 8.1 mM) on maximal Ca(2+)-activated force and Ca2+ sensitivity were studied in rat myocardial preparations rendered permeable by various methods. In preparations permeabilized either by mild homogenization or by saponin (50 micrograms/ml, 30 min), further disruption of the sarcolemma with 2% Triton X-100 resulted in increased maximal force and Ca2+ sensitivity. When membranes were mechanically disrupted or saponized, each vapor agent caused the myocardium to be more sensitive to Ca2+. In these preparations, maximal force was decreased by halothane but was not affected by enflurane or isoflurane. With cellular membranes completely disrupted by Triton, the previously observed increase in Ca2+ sensitivity caused by enflurane was reduced, whereas that caused by halothane and isoflurane was abolished and maximal force was decreased by halothane and isoflurane but was not affected by enflurane. These results indicate that 1) components associated with the cellular membrane systems normally modulate force in mammalian myocardium, and 2) halothane, enflurane, and isoflurane have complex effects on these components. These results therefore can explain some of the differences in inotropic effects that these agents exert on mammalian myocardium. PMID- 8430851 TI - Role of extracellular UTP in the release of uracil from vasoconstricted hindlimb. AB - The source and function of elevated uracil release during vasoconstriction in the perfused rat hindlimb was investigated. The possibility that uracil release derived from the breakdown of released vasoactive uridine 5'-triphosphate (UTP) was examined. Exogenous UTP was found to be a potent vasodilator in the perfused rat hindlimb, opposing norepinephrine and angiotensin-induced increases in vasoconstriction and oxygen consumption. UTP was rapidly catabolized by the hindlimb to uridine 5'-monophosphate (UMP), uridine, and uracil, which were all devoid of vasoactivity. UTP was similarly catabolized by incubated rat aorta. Degradation of exogenous UTP by perfused hindlimb or aorta was inhibited by alpha, beta-methylene-adenosine 5'-diphosphate (AMP-CP), an inhibitor of ectonucleotidases. However, AMP-CP did not decrease uracil and uridine output by the hindlimb during angiotensin-mediated vasoconstriction and increased oxygen consumption. In particular, simultaneous infusion of AMP-CP with angiotensin did not increase efflux of UMP. Although exogenous UTP is a potent vasodilator in the perfused rat hindlimb, it appears not to be released intact during vasoconstriction. Hence, extracellular UTP is unlikely to be the precursor of the uracil release. PMID- 8430852 TI - Effects of thyroid hormones on cardiac development in oculo. AB - Embryonic rat myocardium was grafted into the anterior eye chamber (in oculo) of adult host rats in a series of two experiments that studied the effects of thyroid hormones [triiodothyronine (T3) and thyroxine (T4)] on heart tissue developing without hemodynamic load. In each experiment, surgical sympathectomy of one eye chamber was used to define possible interactions between thyroid hormones and sympathetic innervation to the graft. In the first experiment, propylthiouracil (PTU, 20 mg/kg sc) greatly suppressed growth and beating rate of whole heart grafts, while excess T4 (0.1 mg/kg sc) transiently increased beating rate but not growth. In the second experiment, T3 (5 mg/21 days, slow-release pellet) failed to promote growth in ventricular grafts. However, the size of atrial grafts in surgically sympathectomized eye chambers was larger in T3 treated compared with control rats. T3 administration increased beating rate in ventricular grafts. In both experiments, thyroid hormone treatments were effective in increasing heart weight-to-body weight ratios in the host rats. The data suggest that exposure to normal levels of thyroid hormones may be necessary for optimal cardiac growth. The data also support the hypothesis that a hemodynamic load is required for thyroid hormone-induced cardiac growth. PMID- 8430853 TI - Possible equilibration of portal venous and central venous pressures during circulatory arrest. AB - The mean circulatory filling pressure technique has been used to assess total body venous tone. It involves measuring central venous pressure (CVP) at 5-8 s following circulatory arrest. This study examines if CVP and portal venous pressure (PVP) equilibrate when circulation is stopped by inflating a balloon implanted in the right atrium. CVP and PVP were measured in the control condition and after intravenous bolus injections of norepinephrine (NE, 1.6 microgram/kg), angiotensin II (ANG II, 1.3 microgram/kg), and isoproterenol (Iso, 0.5 microgram/kg) in conscious and pentobarbital-anesthetized rats. In conscious rats, CVP was similar to PVP after circulatory arrest under conditions of normal, elevated, or reduced vascular tone. In anesthetized rats, CVP was similar to PVP in the control condition and after intravenous bolus injection of NE and Iso but was less than PVP after the administration of ANG II. Therefore, mean circulatory filling pressure may not fully reflect total body venous tone in anesthetized, surgically stressed rats. PMID- 8430854 TI - Endothelium increases medial hydraulic conductance of aorta, possibly by release of EDRF. AB - In eight anesthetized New Zealand White rabbits, the aorta was cannulated in situ for measurement of hydraulic conductance (Lp) at different pressures with and without endothelium. De-endothelialization increased Lp at > or = 75 mmHg but not at 50 mmHg. Because endothelium resists transmural water flow, the endothelium must also increase medial Lp at 50 mmHg. To determine whether this effect results from secretion of endothelial-derived relaxing factor (EDRF), Lp was measured in eight rabbits in the presence and absence of NG-nitro-L-arginine methyl ester (L NAME), an inhibitor of EDRF synthesis. At 50 mmHg L-NAME reduced Lp from 6.79 +/- 2.19 to 2.59 +/- 1.41 (SD) x 10(-8) (P < 0.05, paired Student's t test). After L NAME was removed, Lp returned to its control value. At 125 mmHg L-NAME did not significantly change Lp, although endothelial permeability seemed to increase. L NAME did not affect Lp of nine de-endothelialized vessels at either pressure. An additional five experiments showed that the effect of L-NAME at 50 mmHg was reversed by L-arginine. Eleven additional experiments demonstrated that NG-nitro D-arginine methyl ester does not affect Lp at 50 mmHg. These results indicate that EDRF increases Lp of the rabbit aorta at low pressures. PMID- 8430855 TI - An analysis of variability of left ventricular pressure decay. AB - This study evaluated whether the time course of left ventricular (LV) pressure decay is consistent from beat to beat in the normal heart under tightly controlled experimental conditions. We determined the variability of LV isovolumic relaxation and compared it with that of other hemodynamic parameters. Pressure decay was evaluated using a monoexponential time constant (T), a half time (T1/2), and an average rate (Ravg) in nine chronically instrumented dogs. To eliminate physical factors that could lead to variability, the dogs were studied at paced heart rates after autonomic blockade and during apnea. At a heart rate of 160 beats/min the coefficient of variation (SD/mean, expressed as a percent) was higher for T (4.7%, P < 0.005), T1/2 (5.0%, P < 0.005), and Ravg (3.2%, P < 0.005) than for dP/dtmax (1.9%), as well as for end-diastolic volume (1.2%), end systolic volume (1.2%), or end-systolic pressure (1.8%). Similar differences were present at 200 beats/min. Pressure decay was also assessed during major loading shifts induced by rapid caval occlusion. Surprisingly, comparison of first and last beats did not show significant differences for T or T1/2 but did for all standard hemodynamic parameters and for Ravg. While the best correlation with a relaxation parameter and hemodynamic parameters during changing loading conditions was for Ravg, the correlations were not consistent in every case. We conclude that LV pressure decay shows marked variability, unrelated to the algorithm used to assess it. Ravg, a model independent parameter, may be a useful way to quantify LV pressure fall. PMID- 8430856 TI - Repeated reflection of waves in the systemic arterial system. AB - Traditional analysis of pulse-wave propagation and reflection in the arterial system treats measured pressure and flow waves as the sum of a single forward wave (traveling away from the heart) and a single backward wave (traveling toward the heart). The purpose of this study was to develop a more general wave reflection theory that allows repeated reflection of these waves. The arterial system was modeled as a uniform viscoelastic tube terminating in a complex load with reflections occurring at the tube load interface and the heart tube interface. The resulting framework considers the forward wave to be the sum of an initial wave plus a series of antegrade waves. Similarly, the backward wave is the sum of a series of retrograde waves. This repeated reflection theory contains within it the traditional forward/backward wave reflection analysis as a special case. In addition, the individual antegrade and retrograde waves, at the tube entrance, are shown to be independent of the tube length. Aortic pressure and flow data, from dog experiments, were used to illustrate the phenomenon of repeated reflections. Alteration of the arterial system loading conditions, brought about through pharmacological intervention, affected the number and morphology of repeated waves. These results are compared with those found in traditional forward/backward reflection analysis. PMID- 8430857 TI - Regulated secretion of atrial natriuretic factor from cultured ventricular myocytes. AB - We have investigated endothelin (ET)-regulated secretion of atrial natriuretic factor (ANF) from primary neonatal rat ventricular myocytes, where hormone release is thought to be constitutive. In a dose-dependent, nifedipine-sensitive manner, ET acutely enhanced ANF release by two- to fivefold over control cultures within 15 min of agonist exposure, demonstrating that ventricular myocytes display a primary characteristic of a regulated secretory cell type. Unlike atrial cultures, ET enhanced ANF release during the first 30 min of exposure; thereafter, secretion rates returned to control levels. KCl, however, effectively enhanced ANF release only during the first 15 min of exposure. Subcellular fractionation of ventricular culture homogenates did not reveal atrial-type dense secretory granules, and pulse-chase labeling experiments showed that the transit time of newly synthesized ANF was short in ventricular myocytes [time required for half of labeled ANF to be released from cells (t1/2) = 0.5-1.5 h) compared with atrial myocytes (t1/2 = 4 h). These results suggest that, whereas ventricular myocytes possess some of the characteristics of a constitutively secreting cell type (e.g., few, if any, dense secretory granules and rapid transit time for newly synthesized hormone); however, they also display the capacity for regulated secretion of ANF in response to the physiological agonist ET. PMID- 8430858 TI - Sublethal ischemia alters myocardial antioxidant activity in canine heart. AB - We examined antioxidant activity in the pre-conditioned canine myocardium with four 5-min episodes of regional ischemia and reperfusion. Immediately after repetitive brief ischemia, mitochondrial Mn-superoxide dismutase (SOD) activity in the ischemic myocardium significantly increased compared with that in the nonischemic myocardium (18.7 +/- 2.1 vs. 14.9 +/- 1.0 U/mg protein, P < 0.05). Although no difference was seen in the activity between these regions after 3 h of the sublethal ischemia, a significant increase in the activity of the ischemic myocardium reappeared after 24 h compared with that of the nonischemic myocardium (26.7 +/- 0.9 vs. 20.8 +/- 0.9 U/mg protein, P < 0.05). Mn-SOD content increased gradually in the ischemic myocardium after sublethal ischemia, with a peak after 24 h (2.8 +/- 0.1 vs. 2.1 +/- 0.1 microgram/mg protein, P < 0.05). There were no differences in the activity and content of Cu, Zn-SOD between these regions after sublethal ischemia. Activities of glutathione peroxidase and reductase were significantly higher and lower, respectively, in the ischemic myocardium than those of the nonischemic myocardium immediately after repetitive brief ischemia, but no differences between these regions were seen in activities after 3 or 24 h. These results indicate that a brief ischemic insult alters myocardial antioxidant activity not only immediately after but also 24 h after sublethal ischemia. PMID- 8430859 TI - Alterations of mature arterioles associated with chronically reduced blood flow. AB - Adaptive responses of mature arterioles were examined after a 38% reduction in total blood flow to the cremaster muscle produced by unilateral orchidectomy in 12-wk-old rats. Four weeks later, the muscle was smaller than the contralateral cremaster, which did not increase in size during this period. Measured by closed circuit television microscopy, the internal diameters of first- through fourth order arterioles (1A-4A) were smaller, but wall cross-sectional area was reduced only in 3As. The smaller diameter of the 1A in the orchidectomy muscle resulted in unchanged wall shear rate. As determined from the perfusion-fixed, microfilled cremaster muscles, the total length of the arcading arterioles and the number of 3As were not statistically different, but the total number of 4As was significantly reduced on the orchidectomy side. Therefore, chronic load reduction in a mature muscle resulted in reduced blood flow, decreased number of 4As, and smaller arteriolar internal diameters in the absence of net changes in vascular wall cross-sectional area. A local autoregulatory mechanism related to flow induced shear stress is suggested as the mechanism mediating the changes. PMID- 8430860 TI - Differential effects of nitric oxide synthesis inhibitors on vascular resistance and responses to acetylcholine in cats. AB - The effects of dose and the duration of treatment with N omega-nitro-L-arginine (L-NNA) and N omega-nitro-L-arginine methyl ester (L-NAME) on vascular resistance and the vasodilator response to acetylcholine (ACh) were investigated in the hindquarters vascular bed of the cat under constant flow conditions. L-NNA and L NAME increase perfusion pressure and reduce vasodilator responses to ACh in the hindquarters vascular bed; however, the dose and time of exposure required to produce these effects are different. When L-NNA (2.5-5 mg/min) was infused into the hindquarters vascular bed, the increase in perfusion pressure was observed 10 min after onset of the infusion, at which time responses to ACh were not changed. The time of exposure for 50% of the maximal change in hindquarters perfusion pressure was significantly less than the time of exposure for 50% of the maximal decrease in the vasodilator response to ACh during infusion of L-NNA. A similar pattern was observed after the intravenous administration of 3-300 mg/kg L-NAME, while 1 mg/kg L-NAME produced a large but submaximal pressor response and lesser decreases in responses to ACh. The arginine analogues did not completely inhibit the vasodilator response to ACh in the hindquarters vascular bed, with a 30-fold increase in dose producing no additional blockade; however, L-NNA completely inhibited the relaxant response to ACh in the isolated aorta of the cat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430861 TI - Effect of vasopressin on left ventricular performance. AB - We assessed the effect of arginine vasopressin (AVP) on left ventricular (LV) performance in eight conscious dogs. Five minutes after AVP infusion (6 microns.kg-1 x min-1 for 2 min) the plasma AVP was elevated from 3.9 +/- 0.9 to 14.7 +/- 4.6 pg/ml (P < 0.05). With all reflexes intact, AVP caused significant increases in LV end-systolic pressure (P) (112 +/- 8 vs. 122 +/- 7 mmHg, P < 0.05) end-systolic volume (V) (30 +/- 5.8 vs. 38 +/- 7.7 ml, P < 0.05), total systemic resistance (6.2 +/- 1.8 vs. 10.6 +/- 4.0 mmHg.dl-1 x min, P < 0.01) and arterial elastance (Ea) (6.8 +/- 3.0 vs. 8.6 +/- 3.9 mmHg/ml, P < 0.05), while the heart rate (110 +/- 6 vs. 82 +/- 10 beats/min, P < 0.05) and stroke volume (16.5 +/- 4.3 vs. 14.2 +/- 3.9 ml, P < 0.05) were decreased. There was no significant change in the coronary sinus blood flow (82 +/- 19 vs. 78 +/- 22 ml/min, P = not significant). AVP decreased the slopes of LV end-systolic P-V relation (10.7 +/- 1.1 vs. 8.1 +/- 1.9 mmHg/ml, P < 0.05), the maximal first derivative of LV pressure (dP/dtmax)-end-diastolic volume (VED) relation (135.2 +/- 18.7 vs. 63.1 +/- 7.7 mmHg.s-1 x ml-1, P < 0.05), and the stroke work-VED relation (81.1 +/- 4.1 vs. 66.7 +/- 2.8 mmHg, P < 0.05) and shifted the relations to the right, indicating a depression of LV performance. A similar increase in Ea produced by methoxamine did not depress LV performance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430862 TI - Myocardial adenosine, flow, and metabolism during adenosine antagonism and adrenergic stimulation. AB - Relationships between interstitial transudate adenosine and coronary flow and between global adenosine formation and cytosolic metabolism were examined in constant-pressure perfused guinea pig hearts during norepinephrine (NE) stimulation and adenosine antagonism with 10 microM 8-phenyltheophylline. Basal coronary flow was 5.7 ml.min-1 x g-1, and transudate and venous adenosine levels were approximately 0.26 and 0.06 microM, respectively. During 10 min of NE stimulation (15 nM), coronary flow and adenosine levels increased, the phosphocreatine-to-inorganic phosphate ratio ([PCr]/[Pi]) declined, and ATP and pH remained stable. Despite phasic release of adenosine, coronary flow correlated dose dependently with transudate adenosine, and adenosine release was inversely related to [PCr]/[Pi] under all conditions. 8-Phenyltheophylline infusion attenuated functional hyperemia by approximately 40%, enhanced the fall in [PCr]/[Pi], and potentiated elevations in transudate and venous adenosine. Similar results and correlations were obtained in hearts perfused at a constant flow of 5.7 ml.min-1 x g-1, although stimulated adenosine levels and metabolic changes were greater and contractile responses smaller. These data indicate that: 1) endogenous adenosine plays a primary role in functional hyperemia in perfused guinea pig heart; 2) global adenosine formation appears related to phosphorylation status; and 3) adenosine receptor antagonism enhances metabolic disturbances during adrenergic stimulation and markedly potentiates adenosine release, indicating that the functional effects of antagonists may significantly underestimate the dilatory role of endogenous adenosine. PMID- 8430863 TI - Action of C-type natriuretic peptide in isolated canine arteries and veins. AB - C-type natriuretic peptide (CNP) is a hormone that shares structural homology to atrial natriuretic peptide (ANP); however, distinct receptors have been found for each in cultured aortic endothelial and smooth muscle cells. CNP in vivo reduces arterial pressure, atrial pressures, and cardiac output. These actions are consistent with a decrease in cardiac preload. Therefore, the current studies were designed to test the hypothesis that CNP is a vasodilator distinct from ANP. Rings of canine renal and saphenous arteries and renal, saphenous, and femoral veins with and without endothelium were suspended to measure isometric force in an organ chamber. CNP caused significant concentration-dependent relaxations in veins with and without endothelium contracted with phenylephrine (10(-6) log M). In marked contrast, ANP caused no significant relaxation in veins either with or without endothelium. In arterial rings, responses to the peptides were heterogeneous. ANP caused relaxation in renal but not saphenous arteries. CNP induced modest and comparable relaxation in rings of saphenous but not renal arteries with and without endothelium. These results demonstrate that: 1) CNP and not ANP is a relaxing factor of isolated peripheral canine veins, and 2) the responses of arteries to ANP and CNP are heterogeneous. These findings support a distinct biological role for CNP in the regulation of cardiovascular tone. PMID- 8430864 TI - Alpha-adrenergic modulation of transient outward current in hyperthyroid rabbit myocytes. AB - The alpha 1-adrenergic modulation of the transient outward potassium current (I(t)) was studied in single cardiac myocytes obtained from normal (euthyroid) and hyperthyroid rabbits. Rabbits were made hyperthyroid by four or five daily intraperitoneal injections of 0.4 mg/kg body wt thyroxine. Currents were recorded using the whole cell, suction-electrode, voltage-clamp method. It was found that the alpha-adrenergic agonist methoxamine attenuates I(t) in rabbit ventricular cells, as reported earlier for atrial cells. This attenuation is significantly reduced in the hyperthyroid state. For example, 0.2 mM reduces I(t) magnitude (at +20 mV) by close to 40% in euthyroid cells and by only 20% in the hyperthyroid cells. Half-maximal effective concentration values (extrapolated) are close to 0.4 mM in normal and 1 mM in hyperthyroid cells. Preliminary results show similar effects in atrial cells as well. These results may be related to a decrease in the density of membrane alpha-adrenergic receptors in hyperthyroid conditions, or to the induction of a new class of I(t) channels that is less sensitive to alpha agonists. PMID- 8430865 TI - Regional variation in resistance artery diameter responses to alpha-adrenergic stimulation during pregnancy. AB - Whole animal pressor responses are blunted during pregnancy; yet, uterine arteries, paradoxically, become significantly more sensitive to the constrictor effects of phenylephrine (PE). The objectives herein were to investigate 1) the regional variation (uterine vs. mesenteric arteries) in dose-lumen diameter relationship to alpha-adrenergic stimulation during pregnancy, and 2) the selectivity of these sensitivity shifts for this pathway (PE vs. KCl). Lumen diameter was measured in isolated, pressurized (50 mmHg) arterial segments from age-matched virgin (nonpregnant; NP) and late pregnant (LP; days 19-20) Sprague Dawley rats. Uterine arcuate vs. mesenteric arteries from NP rats were equally sensitive to either vasoconstrictor. Arcuate arteries from LP rats, however, were 4.5-fold more sensitive to PE (P < 0.01) compared with those from NP controls. Furthermore, diameter curves became superimposed at [PE] > or = 0.1 microM, even though initial diameter of arcuate arteries from LP rats was significantly larger (P < 0.001). Conversely, mesenteric arteries from LP rats were three-fold less sensitive to PE (P < 0.02), and the diameter curve displayed a corresponding parallel rightward shift. Pregnancy did not affect the sensitivity to KCl depolarization in either arcuate or mesenteric arteries. The percent reduction in lumen diameter to the maximum [KCl] was significantly decreased only in arcuate arteries from LP rats (P < 0.001). Thus, during pregnancy, divergent constrictor responses specific to alpha-adrenergic stimulation occur in resistance arteries from the uterine vs. splanchnic circulations. Consequently, concentrations of PE that are subthreshold in NP uterine arteries can elicit large changes in lumen diameter and thereby have a pronounced effect on uterine vascular resistance in the pregnant state. PMID- 8430867 TI - Regional finite deformations of in situ canine pericardium. AB - The purpose of this study was to determine in situ regional pericardial strains over a wide range of conditions. In five open-chest, anesthetized dogs we examined deformations from biplane cineradiographs of three sets of four 1-mm diameter steel beads glued to basal, midanterior, and apical regions of the pericardium during extremes of pericardial sac sizes (inferior vena caval occlusion, baseline, and tamponade). Finite deformation theory was used to determine the planar components of the Green's strains referenced to the completely unloaded, excised pericardium at the end of each experiment. From the Green's strains the principal components, EI and EII, and the principal direction of strain were determined. The first strain invariant, I1 = EI + EII, in the basal, anterior, and apical regions during caval occlusion (1.27, 0.73, and 0.67) did not differ significantly from those in the baseline state (1.43, 0.86, and 0.76) but increased significantly (P < 0.01) during tamponade to 1.54, 1.30, and 1.08, respectively. Using end systole during inferior vena cava occlusion as a reference, the directions of principal strain in each region during each condition were aligned parallel to the spine pointing toward the tail except at the base during tamponade when there was a 70 degree rotation toward the left limb. The in situ dog pericardium is considerably strained by the underlying heart even during inferior vena cava occlusion, suggesting that a completely unloaded state cannot be achieved in situ. The regional differences in the direction but not the value of principal strain suggest that there are either regional variations in loading or material properties. PMID- 8430866 TI - Role of ATP-sensitive potassium channels in the basilar artery. AB - This study examined the hypothesis that activation of ATP-sensitive potassium channels produces vasodilation and contributes to dilator responses of the basilar artery to acetylcholine in vivo. Diameter of the basilar artery (baseline diam = 245 +/- 14 microns, means +/- SE) was measured through a cranial window in anesthetized rats. RP52891 (1 microM), a direct activator of ATP-sensitive potassium channels, increased the diameter of the basilar artery by 33 +/- 5%. Glibenclamide (1 microM), an inhibitor of ATP-sensitive potassium channels, did not alter baseline diameter but abolished responses of the basilar artery to RP52891. Topical application of acetylcholine (10 microM) for 3 min produced peak dilatation of 33 +/- 6% at 30 s and produced a sustained increase in diameter of 17 +/- 4%. Glibenclamide did not inhibit dilator responses of the basilar artery to acetylcholine. Nitro-L-arginine methyl ester (10 and 100 microM), which inhibits synthesis of endothelium-derived relaxing factor (EDRF), produced concentration-dependent inhibition of dilatation of the basilar artery in response to acetylcholine. Thus ATP-sensitive potassium channels are functional but do not appear to influence basal tone of the basilar artery. Dilator responses of the basilar artery to acetylcholine are dependent on formation of EDRF but not dependent on activity of glibenclamide-sensitive potassium channels. PMID- 8430868 TI - Sympathetic stimulation alters left ventricular relaxation and chamber size. AB - Alterations in left ventricular (LV) contractility, relaxation, and chamber dimensions induced by efferent sympathetic nerve stimulation were investigated in nine anesthetized open-chest dogs in sinus rhythm. Supramaximal stimulation of acutely decentralized left stellate ganglia augmented heart rate, LV systolic pressure, and rate of LV pressure rise (maximum +dP/dt, 1,809 +/- 191 to 6,304 +/ 725 mmHg/s) and fall (maximum -dP/dt, -2,392 +/- 230 to -4,458 +/- 482 mmHg/s). It also reduced the time constant of isovolumic relaxation, tau (36.5 +/- 4.8 to 14.9 +/- 1.1 ms). Simultaneous two-dimensional echocardiography recorded reductions in end-diastolic and end-systolic LV cross-sectional chamber areas (23 and 31%, respectively), an increase in area ejection fraction (32%), and increases in end-diastolic and end-systolic wall thicknesses (14 and 13%, respectively). End-systolic and end-diastolic wall stresses were unchanged by stellate ganglion stimulation (98 +/- 12 to 95 +/- 9 dyn x 10(3)/cm2; 6.4 +/- 2.4 to 2.4 +/- 0.3 dyn x 10(3)/cm2, respectively). Atrial pacing to similar heart rates did not alter monitored indexes of contractility. Dobutamine and isoproterenol induced changes similar to those resulting from sympathetic neuronal stimulation. These data indicate that when the efferent sympathetic nervous system increases left ventricular contractility and relaxation, concomitant reductions in systolic and diastolic dimensions of that chamber occur that are associated with increasing wall thickness such that LV wall stress changes are minimized. PMID- 8430869 TI - Effects of temperature and pH on cardiac myofilament Ca2+ sensitivity in rat and ground squirrel. AB - Chemically skinned papillary muscles from active and hibernating ground squirrels were used to determine whether the enhanced cardiac contractility observed in hibernation is due to a change in myofilament Ca2+ sensitivity. A similar preparation from rats was used to reflect the changes in a nonhibernator. When examined at pH 7.00 in all three groups and under physiological pH with varying temperatures in the ground squirrels, the calcium concentration at which muscle tension is at 50% maximum (pCa2+50) decreased significantly (P < 0.05) with decreasing temperature (25, 15, and 5 degrees C). When hibernating and active ground squirrels were compared, no significant difference in pCa2+50 was observed at 25 degrees C; however, the values at 15 and 5 degrees C were significantly higher (P < 0.05) in the hibernating squirrels. The results indicate that cardiac myofilament Ca2+ sensitivity decreases significantly at low temperature in both active and hibernating ground squirrels; however, the higher Ca2+ sensitivity in the hibernating squirrels at 15 and 5 degrees C could partially contribute to the enhanced cardiac contractility typically seen during hibernation. PMID- 8430870 TI - Effect of beta-endorphin on sympathetic nerve activity to interscapular brown adipose tissue. AB - beta-Endorphin was injected into the third cerebroventricle to investigate its effects on sympathetic nerve activity to interscapular brown adipose tissue (IBAT) in rats. Multiunit discharges of sympathetic nerves to IBAT were recorded electrophysiologically in anesthetized rats. The intracerebroventricular injection of beta-endorphin (125, 250, and 500 pmol/rat in 10 microliters) suppressed sympathetic nerve activity in a dose-related fashion (-23.9 +/- 20.4, 38.7 +/- 7.1, and -66.7 +/- 7.6% 30 min after injection) compared with preinjection baseline. N-acetyl-beta-endorphin (250 pmol) had no effect on sympathetic nerve activity to IBAT. The intraperitoneal injection of naloxone (5.0 mg/rat) did not affect sympathetic nerve activity, but preinjection of naloxone inhibited the suppressive effect of intracerebroventricular injection of beta-endorphin (250 pmol). We conclude that the intracerebroventricular administration of beta-endorphin suppressed the sympathetic nerve activity to IBAT through opioid receptors. The results of this experiment are consistent with the hypothesis that beta-endorphin has a reciprocal effect on food intake and the sympathetic nervous system. PMID- 8430871 TI - Glucagon acts in the liver to control spontaneous meal size in rats. AB - To determine the site of origin of pancreatic glucagon's inhibitory effect on spontaneous feeding in rats, glucagon was infused into either the hepatic portal vein or the inferior vena cava during spontaneous meals late in the dark phase. Hepatic portal infusion of 1.7-13.6 micrograms glucagon/meal reduced spontaneous meal size. In contrast, these doses did not significantly affect meal size when delivered via vena caval catheters that ended near the junction of the hepatic vein. This difference indicates that glucagon receptor sites in the liver initiate the satiating action of glucagon during spontaneous meals. The vagal dependency of glucagon satiety was also tested. Hepatic portal infusion of 13.6 micrograms glucagon/meal reduced the size of spontaneous meals both early and late in the dark in neurally intact rats, but not in hepatic-vagotomized rats. Finally, antagonism of endogenous glucagon with hepatic portal infusion of glucagon antibodies in a dose sufficient to neutralize 1 ng glucagon in vitro increased spontaneous meal size in intact rats, but not in hepatic-vagotomized rats. Thus the satiating effects of both exogenous and endogenous glucagon on spontaneous food intake appear to depend on the hepatic branch of the vagus. Taken together, these results are consistent with the hypothesis that glucagon acts in the liver to produce a satiety signal that is transmitted to the brain by the hepatic branch of the abdominal vagus. PMID- 8430872 TI - The Zucker fatty (fa) gene is not a mutation of corticotropin-releasing factor. AB - Corticotropin-releasing factor (CRF) appears to regulate several physiological systems that display prominent abnormalities in Zucker fatty (fa/fa) rats, including the hypothalamic-pituitary-adrenal axis, the autonomic nervous system, and feeding behavior. Moreover, central administration of CRF ameliorates the obese phenotype. In light of these observations, the gene for CRF is a plausible candidate for the defective gene in the Zucker fatty rat. We report here the use of molecular genetic linkage analysis to test the hypothesis that fa is a mutant allele of the CRF gene. A restriction fragment length polymorphism for CRF between Zucker (13M) and Brown Norway (BN) DNA allowed us to examine segregation of 13M and BN CRF alleles relative to fa in 58 obese (fa/fa) F2 progeny of a 13MBN fa/+F1 intercross. If fa = CRF, all animals homozygous for the fatty mutation should be homozygous for the 13M CRF allele. However, only 10/58 fa/fa animals were homozygous for the 13M CRF allele, indicating that fa and CRF are not allelic. Thus, although CRF may be important in the physiology of Zucker rat obesity, fa is not a CRF mutation. Using a mouse C57BL/6J Spretus F1 x C57BL DBA/2J F1 intercross, we were able to demonstrate that the mouse CRF gene is linked to the carbonic anhydrase II (Car-2) gene on mouse chromosome 3, in a region of synteny-homology with rat chromosome 2. Thus the rat CRF gene is probably located on chromosome 2. PMID- 8430873 TI - Prolactin and testosterone inhibit torpor in Siberian hamsters. AB - Female Siberian hamsters maintained in a winter photoperiod (8 h light/day) ceased to undergo daily torpor during infusion of prolactin (PRL) from osmotic minipumps; winter torpor was reinstated within 3 days of discontinuation of treatment. By contrast, PRL infusion was ineffective in suppressing daily torpor elicited by restricting food intake in female hamsters housed in a summer photoperiod (16 h light/day). Summer daily torpor was, however, completely inhibited in long-day gonadectomized male hamsters treated with testosterone (T). We suggest that the hyperprolactinemia, which in previous studies is characteristic of hamsters that sustain ablation of the suprachiasmatic nucleus, is incompatible with winter torpor. Summer torpor may be controlled by a mechanism less responsive to variations in plasma PRL concentration. Both winter and summer torpor are inhibited by exogenous T; it remains uncertain, however, whether sustained decreases in endogenous T secretion are as essential for the expression of summer as they are for winter torpor. PMID- 8430874 TI - Effects of furosemide or acetazolamide infusion on renal handling of lithium: a micropuncture study in rats. AB - Renal lithium (Li) handling was studied by micropuncture at the late proximal (LPT) and early distal (EDT) tubules in control rats and rats infused with furosemide (FUR) or acetazolamide (ACTZ). In control rats, the tubular fluid-to plasma Li concentration ratio [(T/P)Li] at the LPT exceeded unity (1.05 +/- 0.02, P < 0.05). Some 25% of the filtered load (FL) of Li and water was reabsorbed in proportion between the LPT and the EDT, and consequently the (T/P)Li at the EDT (1.03 +/- 0.03) did not change. FUR inhibited Li reabsorption in the proximal convoluted tubules (PCT), by approximately 7% of the FL. Reabsorption of Li and water in the loop segment was also inhibited, virtually in proportion, by approximately 10% of the FL. These data suggest that FUR-sensitive Li reabsorption in the loop mainly takes place in the pars recta. However, a small increase in the (T/P)Li at the EDT (to 1.10 +/- 0.01) suggested inhibition of some Li transport (approximately 2% of the filtered load of Li) without water, most likely in the thick ascending limb (TAL). In the PCT, ACTZ reduced Li reabsorption by approximately 16% of its FL. Although it is likely that ACTZ also inhibited the pars recta, net Li reabsorption in the loop was not reduced. This suggests that TAL Li reabsorption can compensate for increased delivery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430875 TI - Suppression by central AVP of prostaglandin E1 hyperthermia in one-kidney, one clip Goldblatt hypertensive rats. AB - We have investigated the ability of the one-kidney, one-clip (1K,1C) hypertensive rat to develop a hyperthermic response to intracerebroventricular injection of prostaglandin (PG) E1. Accordingly, core temperature was monitored in response to PGE1 injections both preoperatively and on days 4, 8, 12, and 18 after either unilateral nephrectomy or the induction of hypertension due to nephrectomy plus renal artery clipping. Temperature responses to PGE1 were similar throughout each test day in normotensive, unilaterally nephrectomized control rats. In contrast, 1K,1C rats became hypertensive within 4 days of renal artery clipping, and at this time the hyperthermic response to PGE1 was virtually abolished. A reduced hyperthermic response was also seen at 8 and 12 days after clipping; by 18 days responses were again similar to controls. To determine whether central arginine vasopressin (AVP) was involved in the suppression of the hyperthermic response, we pretreated other hypertensive rats centrally with the V1-AVP antagonist [d(CH2)5Tyr(Me)]AVP before PGE1 injection. In 1K,1C animals thus treated, temperature responses 4-12 days after clipping were indistinguishable from those of similarly treated normotensive control rats. We suggest that the reduced hyperthermic responses to PGE1 seen in the 1K,1C rats during the initial development of hypertension may be due to activation of brain AVP pathways. PMID- 8430876 TI - Effects of intracranial self-stimulation on selected physiological variables in rats. AB - The purpose of this investigation was to characterize selected metabolic, cardiovascular, and hormonal responses to reinforcing intracranial self stimulation (ICSS) of the ventral tegmental area (VTA) in rats. Twenty male Sprague-Dawley rats were stereotaxically implanted with bipolar electrodes aimed at the VTA of the brain. Rats were trained to lever-press for ICSS for 1 wk. While they adapted to the experimental environment by sitting in a metabolic operant chamber, they were connected to the electrode cable but did not lever press. All animals were instrumented with arterial catheters. Rats receiving contingent stimulation (C-St; n = 10) performed 30 min of lever pressing in the metabolic operant chamber for reinforcing brain stimulation. Oxygen consumption (VO2), heart rate (HR), mean arterial pressure (MAP), and rectal temperature (Trec) increased with the onset and continuation of contingent brain stimulation over 30 min (P < 0.05). In addition, plasma norepinephrine (NE), epinephrine (Epi), and corticosterone increased significantly above resting values in C-St rats (P < 0.05). Five animals received investigator-delivered reinforcing brain stimulation (noncontingent stimulation; NC-St), with MAP, HR, VO2, NE, and Epi increasing significantly above resting values (P < 0.05). Trec and corticosterone were not responsive to noncontingent brain stimulation. With the exception of HR, nonstimulated controls (n = 5) did not experience increases above resting values in any of the variables measured. The responses suggest that contingent brain stimulation reward elicits heightened sympathetic arousal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430877 TI - Secretagogue-induced 86Rb+ efflux from bovine parotid is HCO3- dependent. AB - Muscarinic agonist (carbachol)-induced K+ loss from a bovine parotid mince was studied using 86Rb+ as a K+ marker. In contrast to our previous studies with the rat parotid [Am. J. Physiol. 261 (Gastrointest. Liver Physiol. 24): G111-G118, 1991] in which both Cl(-)-dependent and HCO3(-)-dependent components of carbachol induced 86Rb+ efflux were observed, no significant evidence for Cl(-)-dependent 86Rb+ loss was detected in the bovine parotid. HCO3(-)-dependent agonist-induced 86Rb+ loss was blunted by K+ and Cl- channel blockers and by removal of extracellular Ca2+, consistent with the hypothesis that this 86Rb+ loss occurs via a Ca(2+)-activated K+ channel and that this cation loss serves to electrically balance the concomitant loss of HCO3- via an electrically conductive pathway, presumably an apical anion channel. Acetate, formate, and propionate could substitute for HCO3-. Interpreted in terms of current models of salivary fluid secretion, which hypothesize that the production of fluid is secondary to anion secretion accompanied by an electrically coupled K+ loss, these results indicate that salivary production in the bovine parotid is driven almost exclusively by acinar HCO3- secretion. PMID- 8430878 TI - Primary coronary vasodilation associated with pauses in heart rhythm during sleep. AB - We observed 162 episodes of pause in heart rhythm in chronically instrumented dogs primarily during transitions from deep slow-wave sleep to other stages of sleep. These pauses lasted 1.1-8.0 s and were followed by increases in coronary blood flow (CBF) averaging 30% and ranging up to 84%. The postpause surges in CBF do not appear to be mediated by local metabolic factors because the flow surges occurred without significant changes in the heart rate x systolic blood pressure (HRxSBP) product, a standard index of cardiac metabolic activity. Enhanced vagal tone is suggested by the background of marked respiratory sinus arrhythmia, low average heart rates, and the hallmark event, the pause in heart rhythm. In a series of experiments in alpha-chloralose-anesthetized dogs, we demonstrated that direct vagus nerve stimulation can induce both the pause in heart rhythm and the postpause increase in CBF in a pattern similar to that observed during sleep. This response was markedly attenuated after pericoronary denervation. These observations provide suggestive evidence but not definitive proof that enhanced vagal activity may be involved in the increase in CBF after spontaneous pauses in heart rhythm during sleep. PMID- 8430879 TI - Maternal/fetal dehydration: prolonged effects and responses to oral rehydration. AB - Dehydration induces marked alterations in maternal-fetal fluid homeostasis and accompanying fetal endocrine responses. We sought to determine if the increase in fetal plasma arginine vasopressin (AVP) levels during maternal dehydration is mediated by fetal plasma hypovolemia in addition to hyperosmolality and to examine maternal and fetal plasma atrial natriuretic factor (ANF) responses to maternal dehydration and oral rehydration. Seven pregnant ewes (127 +/- 1 day) were water deprived for 72-96 h, and five of these were orally rehydrated. Dehydration induced significant increases in maternal plasma osmolality (pOSM) (300 +/- 2 to 325 +/- 8 mosmol/kg) and AVP (3.0 +/- 0.4 to 18.9 +/- 4.0 pg/ml), and decreases in plasma ANF levels (28.1 +/- 3.1 to 19.7 +/- 3.1 pg/ml). Fetal pOSM (293 +/- 3 to 314 +/- 4 mosmol/kg), AVP (2.5 +/- 0.6 to 8.1 +/- 4.8 pg/ml), and urinary fractional sodium excretion increased significantly, whereas plasma ANF and fetal blood volume did not change. After maternal water access maternal plasma AVP decreased rapidly in comparison to the gradual decrease in maternal pOSM. Fetal plasma AVP levels did not change significantly and fetal pOSM decreased more slowly than maternal pOSM. Fetal plasma ANF increased in association with increased urine flow and glomerular filtration rate after maternal rehydration. These data indicate marked differences in fetal and maternal plasma ANF and AVP responses with dehydration-induced increases in fetal plasma AVP being secondary to plasma hyperosmolality, rather than hypovolemia. Rapid suppression of maternal plasma AVP may contribute to the slower equilibration of fetal pOSM during oral, as compared with intravenous, maternal rehydration. PMID- 8430880 TI - Neuromuscular control of the glottis in a primitive air-breathing fish, Amia calva. AB - The neuromuscular control of the glottis, a muscular sphincter that controls air flow to and from the swim bladder, was investigated using in vitro preparations from bowfin (Amia calva). Stimulation of the ramus intestinalis branch of the vagus nerve caused an increase in isometric tension of the glottal musculature, indicating active closure. The glottis could be actively opened only by direct stimulation of muscle bundles lying lateral to the glottis. In 19 of 24 preparations supramaximal nerve stimulation (20 Hz, 10 V) caused a two-phase increase in muscle tension. Immediately after the onset of stimulation there was a rapid increase in muscle tension. After the end of the train of stimuli, the tension decreased and then again increased briefly followed by a slow return to baseline lasting approximately 60 s. The addition of hyoscine reduced maximum tension of the response by 63 +/- 7% and abolished the second slower element of the response to vagal stimulation. The remaining faster response to nerve stimulation was abolished by tubocurarine. Applied acetylcholine or carbachol mimicked the slow response, causing a slow-onset sustained contraction that was abolished by hyoscine. Hence, the musculature showed physiological characteristics of both skeletal and smooth muscle. Histological examination of the glottis confirmed the physiological results: smooth muscle fibers were found lining the pneumatic duct and lumen of the glottis arranged in a circular fashion around the lateral margins of the glottis. Distinct skeletal muscle bundles were found lateral to the smooth muscle and also arranged in parallel with the glottal lumen, forming a skeletal muscle sphincter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430881 TI - Effects of arterial pressure on drinking and urinary responses to intracerebroventricular angiotensin II. AB - These experiments examined the dipsogenic responses of rats to intracerebroventricularly administered angiotensin II (ANG II) under normotensive and hypotensive conditions. Intravenous infusion of the vasodilator drug minoxidil (25 micrograms.kg-1.min-1), combined with the angiotensin converting enzyme inhibitor captopril (0.33 mg/min), both reduced blood pressure and prevented endogenous ANG II formation. Central infusions with ANG II (4 or 16 ng/h) began 60 min later, and the intravenous and intracerebroventricular infusions ran concurrently for another 90 min. Mean arterial pressure (MAP), water intake, urine volume (UV) and electrolyte excretion were measured throughout. Water intakes to both doses of intracerebroventricular ANG II were increased, and UV and electrolyte excretion were reduced during hypotensive conditions compared with normotensive conditions. Thus the increased water intakes occurred despite increased fluid retention. It is concluded that arterial hypotension enhances the dipsogenic effects of centrally administered ANG II, possibly through baroreceptor-mediated mechanisms. PMID- 8430882 TI - Circadian properties of anticipatory activity to restricted water access in suprachiasmatic-ablated hamsters. AB - This study provides evidence that anticipation of daily water access in hamsters is regulated by nonphotically entrainable circadian oscillators located outside of the suprachiasmatic nuclei (SCN). Intact and SCN-ablated hamsters receiving 2 h/day water access ate large meals (representing 17-55% of daily food intake) during the 2-h access time. Two of nine SCN-intact hamsters, five of five hamsters with partial SCN ablations, and seven of nine hamsters with total SCN ablations showed anticipatory wheel-running rhythms synchronized to water access time. These anticipation rhythms usually disappeared during subsequent ad libitum water access but reappeared when the hamsters were water deprived for 2 days. When the water restriction schedule was shortened to an 18-h interval in six SCN ablated hamsters, an 18-h activity rhythm emerged that usually did not persist during water deprivation. When the schedule was lengthened to 30-h intervals, several hamsters showed 27- to 29-h rhythms that did not stably synchronize to water access time. These results indicate that hamsters, like rats, possess a non SCN-based water- and/or food-entrainable, self-sustaining oscillator with circadian limits to entrainment. PMID- 8430883 TI - Evidence for endothelin-induced renal vasoconstriction independent of ETA receptor activation. AB - Experiments were designed to examine the role of endothelin (ET) receptors, specifically ETA receptors, in mediating the renal vasoconstrictor effects of ET 1 in anesthetized Sprague-Dawley rats. Intravenous infusion of ET-1 at 25 pmol.kg 1 x min-1 for 60 min produced a significant increase in mean arterial pressure (20 +/- 7%) and decreases in renal plasma flow (-60 +/- 6%) and glomerular filtration rate (-47 +/- 6%). Renal vascular resistance was significantly increased from 17 +/- 1 mmHg.ml-1 x min.g kidney wt during control period to 54 +/- 11 mmHg.ml-1 x min.g kidney wt during the experimental period. A second group of rats was infused with both ET-1 and the specific ETA receptor antagonist BQ 123 (0.1 mg.kg-1 x min-1). ET-1-induced increases in mean arterial pressure were completely blocked by BQ-123 (the average change was -7 +/- 4%). However, the renal vasoconstrictor effects of ET-1 were not affected by the antagonist, since renal plasma flow and glomerular filtration rate were again significantly reduced (-54 +/- 4 and -56 +/- 6%, respectively). Once again, renal vascular resistance was significantly increased from 16 +/- 2 mmHg.ml-1 x min.g kidney wt during the control period to 33 +/- 5 mmHg.ml-1 x min.g kidney wt during the experimental period. In a third group, infusion of BQ-123 alone produced a significant decline in mean arterial pressure (-13 +/- 2%), with no significant changes in renal plasma flow or glomerular filtration rate, thus producing a significant decrease in renal vascular resistance (15 +/- 1 vs. 11 +/- 2 mmHg.ml-1 x min.g kidney wt).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430884 TI - Relationship between dietary sodium intake, hemodynamics, and cardiac mass in SHR and WKY rats. AB - To study the effects of sodium intake on circulatory homeostasis and cardiac structure, changes in cardiac mass, systemic hemodynamics, and organ blood flows were determined in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats after 10 wk of controlled dietary intake of low sodium (0.01%), standard sodium (0.44%), and high sodium (2 levels: 1.44 and 4%). Systemic and regional hemodynamics were measured in conscious rats using the radioactive microsphere reference method. The various dietary sodium manipulations did not cause any changes in systemic and regional hemodynamics in the WKY rats. In contrast, the high-sodium diets increased arterial pressure and total peripheral resistance progressively in the SHR rats while decreasing cardiac index, heart rate, and organ blood flows to heart, kidneys, and splanchnic area. The higher sodium intake (4%) increased total and left ventricular mass index in both the SHR and the WKY rats even though hemodynamics of the WKY rats remained unchanged. These data indicate that the high-sodium diet, in addition to producing general vasoconstriction and exacerbation of hypertension, increased cardiac mass further in SHR rats; it also increased cardiac mass in the WKY rats independent of arterial pressure changes, suggesting that high sodium intake may be an independent pathogenetic factor for the development of cardiac hypertrophy. PMID- 8430885 TI - Effects of weight cycling in rats allowed a choice of diet. AB - We examined the effects of weight cycling, produced by bouts of weight loss and regain, on body weight, body composition, dietary fat intake, and energy efficiency. Three groups of adult female Wistar rats were followed for 116 days: control rats (n = 10) were allowed ad libitum access to three mixed diets with protein as a constant proportion of energy and fat provided at 10, 30, and 50% of energy; cycled rats (n = 10) had four bouts of food restriction (50% of baseline intake for 10 days) and refeeding (18-20 days of ad libitum access to the 3 mixed diets); maturity controls (n = 10) were treated identically to controls during the first two cycles and identical to cyclers during the final two weight cycles. At the end of the experiment, we could identify no negative effects of weight cycling on any of the measures taken, and in fact body weight and percentage body fat were lower in cyclers than controls. Dietary fat intake was not altered by weight cycling. In summary, weight cycling did not promote body weight or body fat gain. PMID- 8430886 TI - Differential effects of centrally injected AVP on heart rate, core temperature, and behavior in rats. AB - After intracerebroventricular (icv) injection of arginine-vasopressin (AVP; 0.1, 1, 3, 10, 30 and 100 ng) or artificial cerebrospinal fluid (aCSF), heart rate (HR), core temperature (CT), and gross activity were monitored by a wireless telemetry system in rats in the home cage for a 60-min period. In addition, the simultaneous occurrence of various behaviors was recorded by an observer. Also, two structurally related peptides, oxytocin (OXT) and desglycinamide-arginine vasopressin (DGAVP), were tested (10 and 100 ng). Both the time-effect and dose response relationships of AVP-induced changes in HR and CT were biphasic. Lower doses of AVP produced a tachycardia, whereas injection of higher doses of AVP caused a tachycardia preceded by a significant bradycardia. The concomitant mild rise in CT seen in rats treated with 1 and 3 ng AVP or with aCSF was attenuated in rats given 10 ng AVP; 30 ng AVP resulted in an immediate significant fall in CT, which was restored to control values at 30 min after administration. An inverted U-shaped dose-response relationship was observed for gross activity, locomotion, and rearing behavior, whereas grooming behavior was most marked after the highest dose of AVP. OXT induced a grooming response and cardiac acceleration at the 100-ng dose only, whereas DGAVP produced no effect. To investigate the role of endogenous AVP in the maintenance of tonic ANS activity under resting conditions, rats were treated intracerebroventricularly (icv) with the V1 antagonist d(CH2)5-[Tyr(Me)2]AVP or polyclonal antiserum (W1E) against AVP. During the first 10 min after icv injection of 3 and 10 ng of the antagonist, an increase in HR, CT, and behavioral activation was observed, effects opposite to those produced by the higher dose of AVP. The same variables remained unchanged after administration of 100 ng of the antagonist. W1E injected icv was without effect. In summary, central effects of AVP on autonomic and behavioral activity seem to be mediated by differential neural pathways. In addition, a structure activity relation seems to exist for the AVP-induced effects. Finally, these results suggest that AVP plays but a minor role in the maintenance of tonic activity of the ANS. PMID- 8430887 TI - Cholecystokinin-induced satiety depends on activation of 5-HT1C receptors. AB - To investigate the dependence of the satiating action of cholecystokinin on serotonergic function in rats, we examined the effects of systemic pretreatment with serotonin (5-HT) antagonists of varying selectivity for 5-HT receptor subtypes on suppression of food intake induced by systemic administration of cholecystokinin octapeptide (CCK-8). Mianserin, a 5-HT1C/2-selective antagonist, significantly attenuated the satiating action of CCK-8. Ketanserin, a 5-HT2 antagonist, and three 5-HT3 antagonists, MDL-72222, ICS 205-930, and ondansetron, however, had no effect on the satiating action of CCK-8. These results demonstrate that the satiating action of exogenous CCK depends on activation of 5 HT1 (probably 5-HT1C) receptors and that activation of 5-HT2 or 5-HT3 receptors is not required. PMID- 8430888 TI - Cerebrovascular adaptations to high-altitude hypoxemia in fetal and adult sheep. AB - In the fetus and infant, high-altitude hypoxemia is associated with increased cerebrovascular morbidity. To test the hypothesis that this increased morbidity involves changes in cerebrovascular endothelial and smooth muscle function, we examined middle cerebral, posterior communicating, basilar, and common carotid arteries obtained from 23 normoxic fetuses, 19 hypoxemic fetuses maintained at high altitude (3,820 m) from 30 days gestation to near term (approximately 143 days), 55 normoxic non-pregnant adults, and 24 hypoxemic nonpregnant adults maintained at the same altitude and duration as the hypoxemic fetuses. Long-term hypoxemia was associated with several significant changes in both fetal and adult arteries, including a generalized increase in base-soluble protein (5-50%), a depression of the maximum potassium-induced tensions (16-49%), and a depression of the relaxation responses to S-nitroso-N-acetylpenicillamine (1-11%), which releases nitric oxide into solution upon hydration. Altitude acclimatization significantly enhanced amine-to-potassium ratios (the ratio of tension produced by 10 microM serotonin with 20 microM histamine to that produced by 122 mM potassium) only in adult cerebral arteries (51-87%) and significantly depressed potassium-induced stresses (up to 41%) and serotonin/histamine-induced tensions (20-37%) only in fetuses. Endothelium-dependent relaxations to A23187 were significantly depressed in hypoxemic fetuses (4-11%) but were significantly enhanced in hypoxemic adults (2-14%). We conclude that chronic hypoxemia depresses both vascular smooth muscle and endothelial function to a greater extent in fetal than in adult cerebral arteries and that this effect could contribute to the greater postnatal vulnerability to asphyxic and hypertensive insults seen in hypoxemic neonates. PMID- 8430889 TI - Hypertension in CB57BL/6J mouse model of non-insulin-dependent diabetes mellitus. AB - The C57BL/6J (BL/6) mouse develops non-insulin-dependent diabetes mellitus (NIDDM) when fed a high fat-high simple carbohydrate (HFHSC) diet, whereas A/J mice do not. The purpose of the study was to determine whether hypertension occurred with NIDDM and whether it was sustained by sympathetic nervous system (SNS) hyperactivity. After 3 mo on an HFHSC diet with a low Na content (0.06%), awake, tail-cuff systolic blood pressure (BP) increased 20% above the control diet in BL/6 (138 +/- 3 vs. 115 +/- 4) but not in A/J (115 +/- 6 vs. 113 +/- 2 mmHg) mice. On a normal Na (0.4%)-HFHSC diet, BL/6 mice had a higher BP than on 0.06% Na (149 +/- 3 at 3 mo, 162 +/- 6 at 4.5 mo). After 1 mo on the 0.06% Na HFHSC diet, direct BP of anesthetized BL/6 mice was 18% higher than control. The hypotensive response to interruption of SNS activity by ganglionic blockade (chlorisondamine) increased in the BL/6 mice (50%), whereas the heart rate response increased in both strains (20-30%). Analysis of variance (ANOVA) on glucose detected significant effects of strain and diet and a strain x diet interaction (P = 0.0007). At 1 or 3 mo, HFHSC-fed BL/6 mice were hyperglycemic (> 11 mM) compared with diet or strain controls. The ANOVA on insulin detected strain and diet effects but not a strain x diet interaction (P = 0.3). HFHSC increased insulin above the control of 140-160 pM in A/J and BL/6 strain (20-70% at 1 mo, 400% at 3 mo).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430890 TI - Blood pressure during routine activity, stress, and feeding in black racer snakes (Coluber constrictor). AB - The pressor response to normal daily behaviors and acute stress was studied in black racer snakes (Coluber constrictor) at 30 degrees C. In addition, hematological changes during the stress response were assessed. Mean nighttime systemic arterial blood pressure (SABP) in undisturbed snakes was lower than daytime pressure (26 +/- 3 vs. 32 +/- 9 mmHg, P < 0.001). When snakes were fed mice, SABP increased 3.5- to 4-fold and heart rate increased approximately 3-fold above resting values within approximately 30 s (peak SABP, 99 +/- 18 mmHg; peak heart rate, 99 +/- 12 beats/min). Killing and ingesting the mice required 6-15 min, during which time mean SABP and heart rate were 84 +/- 16 mmHg and 92 +/- 12 beats/min. Pulmonary blood pressure also increased but remained 40-50 mmHg lower than SABP. During stress elicited by tapping the snakes for 5-8 min, heart rate was 94 +/- 6 beats/min but SABP averaged only 44 +/- 11 mmHg. Plasma norepinephrine and epinephrine increased 51- and 26-fold. Plasma glucose increased 58%, hematocrit increased 19%, and plasma volume decreased 19%. It is concluded that blood pressure is markedly affected by behavior and that the sympathetic nervous system appears to play a key role. PMID- 8430891 TI - Effect of fibronectin on permeability of normal and TNF-treated lung endothelial cell monolayers. AB - Fibronectin is found in a soluble form in plasma and lymph and in an insoluble form in the extracellular matrix. Plasma fibronectin can incorporate into the tissue pool of fibronectin where its adhesive properties may influence cell-cell interaction, cell adhesion to a collagenous matrix, and vascular integrity. Elevation of plasma fibronectin can attenuate the increase in lung vascular permeability in sheep during postoperative gram-negative bacteremia, and plasma fibronectin deficiency can magnify the increase in lung vascular permeability with postoperative sepsis. Using pulmonary endothelial monolayers, we determined if exogenous human plasma fibronectin (pFn) would influence the protein permeability of pulmonary endothelial monolayers as determined by transendothelial clearance (microliters/min) of 125I-albumin after they were exposed to human recombinant tumor necrosis factor-alpha. Treatment of endothelial monolayers with tumor necrosis factor (TNF) (200 U/ml) for 18 h resulted in a significant (P < 0.05) increase in protein permeability. Addition of intact purified human plasma fibronectin to normal confluent endothelial monolayers to yield a medium concentration of 300, 600, and 900 micrograms/ml for 18 h had no effect on baseline protein permeability. In contrast, whereas addition of lower amounts of human plasma fibronectin (300 micrograms/ml) did not attenuate the TNF-induced increase in monolayer permeability, the higher concentrations of 600 or 900 micrograms pFn/ml significantly decreased (P < 0.05) protein permeability. The ability of soluble plasma fibronectin to attenuate the TNF-induced increase in endothelial protein permeability required an incubation time of at least 2-3 h, perhaps due to a lag time required for its incorporation into the extracellular matrix.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430892 TI - Food deprivation- and palatability-induced microstructural changes in ingestive behavior. AB - The effects of 17 h food deprivation and stimulation by five concentrations (0.05 0.8 M) of sucrose solutions on the licking behavior of rats were investigated. Food deprivation increased the intake of the three lowest concentrations (0.05, 0.1, and 0.2 M) but had no effect on the volume ingested of the two highest concentrations (0.4 and 0.8 M). Food deprivation had no significant effect on the duration of the meals of any of the sucrose solutions; rather it affected the rate of ingestion. In those cases where food deprivation did affect volume intake, it did so by increasing the initial rate of ingestion. Although food deprivation had no effect on the volume ingested of the two strongest concentrations of sucrose, it nevertheless affected the ingestive behavior by increasing the duration of the sustained periods of bursts of licking and decreasing their number. Deprivation also significantly decreased the rate of licking within these sustained bouts of licking. The results indicate that food deprivation can affect the ingestive behavior of rats in ways that are not revealed by measuring volumetric intake alone. The data also support the view that food deprivation increases the palatability of the test solutions. PMID- 8430893 TI - Forward-scattering degenerate four-wave mixing as a simple sub-attomole-sensitive nonlinear laser analytical spectrometric method. AB - Optical phase conjugation by "forward-scattering" degenerate four-wave mixing in an absorbing liquid analyte solution is reported as a sensitive and simple nonlinear laser spectroscopic method. Since only two input laser beams are used in this nonlinear four-wave mixing setup, it offers important advantages including ease of optical alignment, efficient use of input photon density, low laser power requirements, and high wave-mixing efficiency. In addition, since the phase-conjugate signal is a laser beam, optical signal detection is very efficient and the signal-to-noise is excellent. Important characteristics of this novel nonlinear laser technique, including signal dependence on analyte concentration, individual input beam power, and modulation frequencies, are examined. Excellent detection sensitivity, small detection volume, and convenient sample introduction promise many applications for this nonlinear laser spectroscopic method. Preliminary detection limits of 0.7 amol of eosin B and 45 amol of iodine inside a probe volume of 98 pL are reported using a forward scattering degenerate four-wave mixing setup. PMID- 8430894 TI - Expert system for data acquisition to achieve a constant signal-to-noise ratio: application to imaging of DNA sequencing gels. AB - Normally, data acquisition and processing in chemical measurements are based on equal time (effort) for each data point. This leads to uneven signal-to-noise ratios (S/N) for each point. We present an expert system which decides in real time whether adequate S/N has been achieved for each point. If so, that data point will be omitted in all further acquisition or processing operations, greatly increasing the overall efficiency. The special case of analyzing DNA sequencing gels is tested with this scheme. A factor of 7.6 reduction in effort is demonstrated for a data set of 384 x 250 pixels, which normally would require 6 million sequential operations (64 frames). PMID- 8430895 TI - Median filtering for removal of low-frequency background drift. PMID- 8430896 TI - Long-term effects of anterograde degeneration on astroglial reaction in the rat geniculo-cortical system as revealed by computerized image analysis. AB - Changes in the expression of glial fibrillary acidic protein by astrocytes in the primary visual cortex of adult albino rats were analyzed with immunohistochemistry after unilateral destruction of the dorsal lateral geniculate nucleus. An increase in number of glial fibrillary acidic protein immunoreactive astrocytes could be detected in the visual cortex of the side ipsilateral to the lesion in the short-term survival group (7-11 days post lesion), but this increase was extremely reduced after a postlesional survival time of 150 days. The quantitation of the glial response by image analysis showed, that the initial increase was mainly localized in the cortical layers II IV, where the geniculo-cortical input terminates. The transient nature of this process was revealed by the measurements in the long-term survival group, where differences between experimental and control sides were substantially reduced. We conclude, that the remote glial response in the visual cortex is transient and that is disappearance indicates the end of a postlesional adaptation period in the neuropil. PMID- 8430897 TI - Differences in the fibronectin-dependence of migrating cell populations. AB - In avian embryos, the migration behaviour of several cell populations, melanoblasts, Schwann cells, myogenic cells and axons after application of antibodies directed against the cell-attachment fragment of fibronectin (alpha CAF) was investigated. The migration of the different cell types was influenced in different ways. 1. Epidermal melanoblasts did not colonize areas into which the antibody had been injected, i.e. distal to the grafting site. They frequently spread proximally to the back and neck, sometimes even as far as to the ipsilateral leg. When grafted to the dorsal side of the wing bud, melanoblasts never spread to the ventral side after injection of the antibody. Non-epidermal melanoblasts continued to migrate distally. 2. Grafted Schwann cells and host axons were not noticeably affected by the antibody injections. Both were found proximally and far distally to the grafting site, i.e. also within the injected area. 3. Myogenic cells were immobilized near the grafting site, where they differentiated biochemically, but sometimes only partially underwent fusion into myotubes. They participated in the formation of host muscle blastemas only immediately adjacent to the non-migratory cell population of the graft such as fibroblasts and cartilage. 4. The injected antibody could be localized up to 5 h after the application in the distal third of the limb bud. We conclude that migrating cell populations show differences in their fibronectin-dependence which probably reflect their use of fibronectin during migration. PMID- 8430898 TI - Optic synapses are found in diencephalic neuropils before development of the tectum in Xenopus. AB - The position of the earliest optic synapses in Xenopus and the stage at which they developed were studied with the electron microscope after labelling of optic axons with horseradish peroxidase. In addition, tritiated thymidine autoradiography and bromodeoxyuridine immunohistology were used to identify the birth dates of cells in the regions where the synapses had been found. The earliest mature optic synapses were found in the mid-diencephalic region, where the major diencephalic optic neuropils were beginning to develop. These synapses were seen at stage 35/36, before cells in the tectal precursor region had become postmitotic. In other animals labelling with tritiated thymidine or bromodeoxyuridine showed that cells in the diencephalon, close to where the synapses had been seen, were becoming postmitotic at the time the earliest optic axons arrived. The first optic synapses to form in the developing Xenopus visual system thus appeared to do so in the neuropil of Bellonci and the rostral visual nucleus. PMID- 8430899 TI - The intramural pelvic nerves immunoreactive for calcitonin gene-related peptide in the rectum of normal and aganglionosis rat. AB - The distribution of calcitonin gene-related peptide-like immunoreactive (CGRP-LI) nerves was investigated immunohistochemically in the rectum of normal, capsaicin treated and congenital aganglionosis rats. The rectum of the normal rat was densely supplied with both extrinsic and intrinsic nerves exhibiting CGRP-like immunoreactivity. Numerous CGRP-LI nerve fibres were seen in both the myenteric and submucous plexuses. Intrinsic CGRP-LI nerve cell bodies were sparsely found in both the ganglionated plexuses, while a large inflow of extrinsic CGRP-LI nerves was characteristically observed in the rat rectum. CGRP-like immunoreactive fibres were abundant in the intramural pelvic nerves which ascend proximally in the intermuscular zone and connect with the myenteric plexus of the rat distal bowel. As compared with CGRP-positive fibres, SP- or SK-positive fibres in the intramural pelvic nerves were far less frequent. The treatment with capsaicin in the neonatal period led to a marked depletion of CGRP immunoreactivity in these extrinsic nerves as well as in the most terminal varicose fibres seen in the whole layers of the rectal wall. These findings suggest that the vast majority of CGRP-LI fibres in the intramural pelvic nerves are sensory in nature, and that the positive nerve fibres of extrinsic origin directly innervate each layer of the rat rectum. These CGRP-LI sensory fibres associated with the intramural pelvic nerves, may be of importance in the regulation of rectal and colonic function in normal rats. A dense innervation of CGRP-LI nerve fibres, some of which showed the varicose appearance, was also found in the rectum of congenital aganglionosis rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430900 TI - Embryonic development of the house shrew (Suncus murinus). II. Embryos at stages 11 and 12 with 13 to 29 pairs of somites, showing limb bud formation and closed cephalic neural tube. AB - The embryonic development of the laboratory house shrew (Suncus murinus) was observed during the period from 13 to 29 pairs of somites and was compared with that of other mammalian species. This period ranged from 10 to 12 days after fertilization. Embryos were allocated to stages 11A-C and 12A-C according to somitic count. These embryos were characterized by the following features. 1. The curvature of the body became gradually enhanced, changing from a parenthesis-like to a bracket-like shape. 2. The swelling of the future hindlimb bud appeared at stage 11A, while the forelimb bud became apparent at stage 12A. The latter developed rapidly and had exceeded the former in size by the end of stage 12C. 3. The timing of closure of the cephalic neuropores varied, but the order of closure is constant. The prosencephalic neuropore closed later. The caudal neuropore still existed even at the end of stage 12C. 4. In all of the cranial nerve ganglia except for the auditory one, crest-derived cells seemed to contribute to the initial formation, while placodal cells seemed to be involved later. A different pattern of primordial formation was observed between trigeminal/facial and glossopharyngeal/vagal ganglia. 5. By the end of stage 12C, the eye cup and nasal pit began to form, and the endolymphatic appendage also appeared. 6. In the heart, the sinus valves were well developed, and the atrium and ventricle were being divided by the developing interatrial septum I and interventricular septum, respectively. 7. The thyroid primordium was temporarily everted and projected into the pharynx. The internal structure of this protruding thyroid resembled "tuberculum thyroideum" observed in the human embryo. PMID- 8430901 TI - Dexamethasone induces chondrogenesis in organoid culture of cell mixtures from mouse embryos. AB - The effect of dexamethasone on morphogenesis and differentiation of cells obtained from mouse embryos grown at high density in vitro was investigated. Cells from decapitated mouse embryos of day 10 to day 13 were isolated by enzymatic treatment and grown at high density at the medium/air interface in organoid culture. After 28 days in culture, organoid-like structures such as vesicles, gland-like structures and cell aggregates had developed, dependent on the stage of the embryos. After the addition of 10(-7) M dexamethasone, cartilage had formed in cultures of cells from day-10, -11 and -12 embryos. It was maximal in cultures of day-11 cells and rare in day-10 cells. No cartilage was found in cultures of day-13 cells. Cartilage induction was similar in cultures treated with 10(-6) and 10(-7) M dexamethasone, but clearly less in cultures treated with 10(-8) M. Only minute amounts of cartilage were detectable after dexamethasone treatment of cells obtained from decapitated embryos (day-11 and -12) whose limb buds had been cut off. In organoid cultures of pure limb bud cells, 10(-7) M dexamethasone had no influence on chondrogenesis. The results indicate that the cells inducible to form cartilage by dexamethasone originate from the limb buds. Glucocorticoid induction of chondrogenesis has not been described in vivo. The dependency of both chondrogenesis and expression of glucocorticoid receptor on cell density in vitro may be the cause for this effect. PMID- 8430902 TI - Serotonin and morphogenesis. Transient expression of serotonin uptake and binding protein during craniofacial morphogenesis in the mouse. AB - This study describes the timecourse of expression of low-affinity serotonin uptake sites in the developing craniofacial region of the mouse embryo. Whole mouse embryos were incubated in the presence of various serotonergic compounds followed by immunocytochemical localization of serotonin (5-HT) and its binding protein. In the gestational day 9 embryo (3-5 somites), 5-HT uptake was observed in the myocardium of the heart, the visceral yolk sac and foregut. A specific and transient pattern of 5-HT uptake was observed in the hindbrain neuroepithelium from day 9.5-11, where it was localized in rhombomeres 2-5 in the day 9.5 embryo. By day 10, when rhombomeres were no longer evident, uptake was present in the dorso-lateral neuroepithelium surrounding the fourth ventricle (rhombic lip; cerebellar anlage). Uptake of 5-HT was initially observed in the surface epithelium of the craniofacial region at day 10 (20-25 somites) and was greatly increased at day 11. The invaginating lens, nasal placode epithelium and otocyst also took up 5-HT at day 11. During these stages a 45 kD serotonin-binding protein (SBP) was expressed in craniofacial mesenchyme, and became progressively restricted to regions subjacent to epithelial uptake sites. These staining patterns were shown to be specific for 5-HT and SBP by their absence in embryos stained using preabsorbed antisera. The timecourse of these patterns are correlated with critical events in craniofacial morphogenesis including (1) onset of inductive epithelial-mesenchymal interactions, (2) invagination and fusion of placodal structures, (3) presence of rhombomeres, and (4) regions of low proliferative activity. PMID- 8430903 TI - Presence of chondroid bone on rat mandibular condylar cartilage. An immunohistochemical study. AB - Immunohistochemical techniques were used to examine the locations of type I and type II collagens in the the most anterior and the posterosuperior regions of the mandibular condylar cartilages of young and adult rats. Large ovoid and polygonal cells, which were morphologically different from any of the neighboring cells, e.g., mature or hypertrophied chondrocytes, osteoblasts, or fibroblasts, were observed at the most anterior margin of the young and adult condylar cartilages. In the extracellular matrix (ECM) of this area, an eosinophilic staining pattern similar to that in bone matrix was observed, while the peripheral ECM showed basophilic staining and very weak reactivity to Alcian blue. Immunohistochemical examination showed that the ECM was stained heavily and diffusely for type I collagen, while a staining for type II collagen was faint and limited to the peripheral ECM. Two different staining patterns for type II collagen could be recognized in the ECM: one pattern revealed a very faint and diffuse reaction while the other showed a wak rim-like reaction. These staining patterns were markedly different from those in the cartilaginous cell layer in the posterosuperior area of the condylar secondary cartilage, which showed faint staining for type I collagen and a much more intense staining for type II collagen. These observations reveal the presence of chondroid bone, a tissue intermediate between bone and cartilage tissues, in the mandibular condylar cartilage, and suggest the possibility of osteogenic transdifferentiation of mature chondrocytes. PMID- 8430904 TI - An electron microscopic study of the harderian gland of the Syrian hamster with particular reference to the processes of formation and discharge of the secretory vacuoles. AB - The lipid-secreting cells of the Harderian gland of the Syrian hamster were studied using light, transmission, and scanning electron microscopy. Three morphologically different secretory cell types are identified in the gland: type I and II cells of the male gland and, distinct from either, the female gland cell. In all secretory cell types, lipid droplets in the cytoplasm were surrounded by unit membranes. Ultrastructural evidence of the involvement of the Golgi apparatus in the formation of the secretory vacuoles was obtained. The process of secretion involved the fusion of the boundary unit membrane of the vacuole with the plasma membrane and the release of the vacuolar content alone into the lumen. No evidence of holocrine processes was observed in this study. In addition to lipids, vacuoles contained materials whose solubility properties clearly differed from those of lipids. There appear to be variations in the ultrastructural characteristics of the vacuole content of the different types of secretory cell. PMID- 8430905 TI - Modulation of the Golgi apparatus in stimulated and nonstimulated prolactin cells of female rats. AB - The three-dimensional structure of the Golgi apparatus and its compartments in prolactin cells has been examined in lactating rats in which secretion of prolactin was suppressed by removing the litter or stimulated by allowing the pups to suckle again. As soon as 2 hr after removal of the litter, large irregular progranules and numerous large pale vesicles accumulated in the trans Golgi area together with vesicular or tubular fragments. The cis-tubular network was no longer recognizable on the cis-face of the Golgi ribbon; the saccules of the midcompartment were partitioned by narrow fissures and also became perforated in register by numerous fenestrations of various sizes and irregular contours. The concomitant appearance of numerous vesicles in the cavities thus formed as well as in the surrounding cytoplasm indicated that they probably arose by the progressive cavitation and fragmentation of saccules of the mid compartment. Such a process, which reached a maximum between 4 and 6 hr after removal of the litter from the mother, was no longer observed at 8 and 12 hr, at which time intervals the Golgi apparatus was reduced in size with no cis-tubular elements and progranules on its trans-aspect and few vesicles in its surroundings. When mothers, separated from their litters for a period of 12 hr, were returned to their pups for 20 min, the cis-tubular network reappeared on the cis-aspect of the Golgi stacks and presumably formed by fusion of vesicles and anastomosed tubules located next to the cisternae of the rough endoplasmic reticulum. In addition, the structure of the midsaccules returned to the stimulated condition, and early progranules were again segregated within the trans-most saccules of the Golgi stack. Hence, the Golgi apparatus of prolactin cells was rapidly and deeply modified in the presence or absence of stimulation. PMID- 8430906 TI - Transport of casein submicelles and formation of secretion granules in the Golgi apparatus of epithelial cells of the lactating mammary gland of the rat. AB - Lactating mammary glands fixed by perfusion with 5% glutaraldehyde subsequently were postfixed with potassium ferrocyanide reduced osmium or were treated with tannic acid. Stained thin sections were examined with the electron microscope and stereopairs were prepared. The distribution of casein submicelles was analyzed in the various components of the Golgi apparatus. The Golgi stacks were composed of five or six elements, all of which contained casein submicelles 20 nm in diameter. The cis-tubular network or cis-element, as well as the underlying three or four midsaccules, showed these casein submicelles either attached to their membrane or free in the lumen. The trans-most element of the stacks formed distended prosecretory granules in which both isolated or clustered casein submicelles were suspended in an electron-lucent fluid. These micellar aggregates increased in size and became progressively more compact to form spherical dense bodies or casein micelles, in which the individual 20 nm particles could easily be resolved. Casein micelles were seen in secretory granules in addition to a wispy material of low density. The numerous small spherical vesicles (80 nm or larger) seen on the cis, lateral, or trans aspects of the stacks did not appear to contain free casein submicelles. This raises questions regarding the role of these vesicles in the transport of casein macromolecules through the Golgi stacks. It was noticeable that in this Golgi apparatus a trans-Golgi network was limited to a few small residual tubules free from casein submicelles. It thus appears that the greater part of the trans-most Golgi element gives rise to the large prosecretory granules. After leaving the Golgi region and prior to exocytosis, the secretory granules often fuse to form larger granules before exocytosis. PMID- 8430907 TI - Promotion of muscle regeneration in the toad (Bufo viridis) gastrocnemius muscle by low-energy laser irradiation. AB - The effect of low-energy laser (He-Ne) irradiation on the process of skeletal muscle regeneration after cold injury to the gastrocnemius muscle of the toad (Bufo viridis) was studied using quantitative histological and morphometric methods. The injured zones in the experimental toads were subjected to five direct He-Ne laser (632.8 nm wavelength) irradiations (6.0 mW for 2.3 min) every alternate day starting on the fourth day postinjury. Muscles that were injured as above, and subjected to red-light irradiation, served as a control group. Morphometric analysis was performed on histological sections of injured areas at 9, 14, and 30 days postinjury. At 9 days postinjury, mononucleated cells populated 69.3% +/- 16.8% of the total area of injury. Thereafter, their volume fraction (percent of total injured zone) decreased gradually but more rapidly in the laser-irradiated muscle than in the control. The volume fraction of the myotubes in the laser-irradiated muscles at 9 days of muscle regeneration was significantly higher (7.0% +/- 2.2%) than in the control muscle (1.2% +/- 0.4%). Young myofibers in the laser-irradiated muscles populated 15.5% +/- 7.9% and 65.0% +/- 9.5% of the injured area at 9 and 14 days of muscle regeneration, respectively, while in control muscles these structures were not evident at 9 days and made up only 5.3% +/- 2.9% of the traumatized area at 14 days postinjury. The volume fraction of the young myofibers further increased by 30 days of muscle regeneration making up 75.7% +/- 13.2% of the traumatized area, while in the laser-irradiated muscles most of the injured zone was filled with mature muscle fibers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430908 TI - The physiological cross-sectional area of motor units in the cat tibialis anterior. AB - The physiological cross-sectional area (CSA) of a motor unit (MU), taken as the sum of fiber areas measured on a single section through the approximate midlength of the MU, has been compared with the physiological CSA more strictly defined as the sum of the maximal areas to be found anywhere along the length of each of the MU fibers. The CSA at intervals along the fiber length was measured in fibers selected from four glycogen-depleted, isolated MUs in the cat tibialis anterior (TA), and profiles of the summed areas made. In one MU, measurements were also taken on all the MU's fibers at less frequent intervals. The profiles demonstrate that the summed CSA based on each fiber's maximum CSA may exceed that derived from observation on any single section by as much as 20%. As a consequence, values that have been reported for specific tension (force per unit area) of MUs in the TA and probably other muscles may have been overestimated, especially for those MUs of fast type. Estimates were also made of the share of the MU's total force transmitted directly to the tendons of origin and insertion via endings of the blunt musculotendinous type as distinct from tapering intrafascicular endings acting through in-series connective tissue and non-MU fibers. In two MUs of slow type in which most fibers ran from tendon to tendon, "partial tapering" extending over 1 cm of the fiber length accounted for a third of the total physiological CSA, and indicated yet another mode for relay of the MU's force to the tendon. PMID- 8430909 TI - Effects of estradiol and progesterone on the cytodifferentiation of epithelial cells in the oviduct of the newborn golden hamster. AB - The effects of estradiol and progesterone on the cytodifferentiation of epithelial cells in the oviduct of the newborn golden hamster were investigated by electron microscopy. Consecutive daily injections of estradiol-17 beta (E2) induced various ultrastructural changes in undifferentiated epithelial cells of the neonatal oviduct. Ciliogenesis, formation of some ciliary buds, and ciliation were frequently observed in the oviductal epithelial cells on days 1-4 of consecutive treatments with E2. On days 2 and 3, the remaining cells contained well-developed Golgi apparatus and rough endoplasmic reticulum. Thereafter, a few secretory granules were observed in the cytoplasm of these cells, indicative of differentiation into secretory cells. Occasionally, secretory cells undergoing ciliogenesis or mitosis were found in the epithelium. On day 9, many fully mature ciliated and secretory cells were observed. Quantitative studies clearly showed that E2 induced the differentiation of both ciliated and secretory cells. By contrast, consecutive daily injections of progesterone significantly stimulated the appearance of ciliogenic and ciliated cells but not that of secretory cells. These results indicate that the induction of differentiation of secretory cells is a specific effect of estrogen, whereas the differentiation of ciliated cells may be closely related to effect of progesterone as well as of estrogen. It is suggested that hormonal effects on differentiation differ between ciliated and secretory cells in the oviductal epithelium of the newborn golden hamster. PMID- 8430910 TI - Observations by scanning electron microscopy of oviductal epithelial cells from cows at follicular and luteal phases. AB - The luminal surfaces of epithelial cells in various regions of the bovine oviduct from cows, at the follicular and luteal phases of the estrous cycle, were examined by scanning electron microscopy. Marked cyclic changes were observed on the surface of the epithelium in the fimbriae and ampulla, but few changes were found in the isthmus and uterotubal junction. The epithelium of the fimbriae and ampulla of oviducts in the follicular phase were densely ciliated, and the cilia concealed the apical processes of the nonciliated cells. In the luteal phase, the nonciliated cells predominated in the epithelium and most of the ciliated cells were hidden by the bulbous processes of the nonciliated cells. The epithelium of the ampullar-isthmic junction showed similar changes, but to a lesser extent. In the isthmus and at the utero-tubal junction, the apical surfaces of the nonciliated cells were flat or gently rounded during the estrous cycle. Quantitative examinations by light microscopy showed that the mean percentage of ciliated cells significantly decreased in the fimbriae and ampulla at the luteal phase, but not in the other regions. The height of ciliated cells decreased dramatically in the fimbriae, ampulla, and ampullar-isthmic junction at the luteal phase. By contrast, the height of nonciliated cells decreased significantly in the ampullar-isthmic junction, isthmus, and utero-tubal junction at the luteal phase, but not in the fimbriae and ampullae. The results demonstrate that there are regional variations and cellular differences in the cyclic changes associated with the oviductal epithelial cells in the cow. PMID- 8430911 TI - Nonciliated cells of the rat efferent ducts endocytose testicular sulfated glycoprotein-1 (SGP-1) and synthesize SGP-1 derived saposins. AB - Sertoli cell sulfated glycoprotein-1 (SGP-1) is a heavily glycosylated and sulfated 70 kDa protein that is secreted into the lumen of the seminiferous tubule where it binds to spermatozoa. Recent light and electron microscope immunocytochemistry has suggested that the testicular SGP-1 detaches from the surface of spermatozoa in the lumen of the efferent ducts to be endocytosed within the endocytic apparatus of the epithelial nonciliated cells. The finding of SGP-1 mRNA together with anti-SGP-1 immunogold labeling of the lysosomal compartment suggest that these cells synthesize an efferent duct form of SGP-1. In the present study, a number of different experimental approaches (ligation, tunicamycin treatment and a combination of both) in combination with quantitative electron microscope immunogold labeling and Western blot analysis were performed in order to test this hypothesis. The number of gold particles and the profile area of the early (endosomes, pale multivesicular bodies) and late (dense multivesicular bodies, secondary lysosomes) endocytic apparatus were estimated in each of the experimental groups and expressed as the number of gold particles per micron 2 (labeling densities). The data revealed that ligation produced a significant reduction of anti-SGP-1 immunogold labeling of the early endocytic apparatus but not of the late endocytic apparatus. Tunicamycin treatment on the other hand produced a significant reduction of immunogold labeling of both the early and late endocytic apparatus. The combination of both treatments resulted in a more effective reduction of the labeling densities of these two endocytic compartments. These results thus indicate that the nonciliated cells of the efferent ducts are involved both in the endocytosis of the Sertoli-derived SGP-1 and in the synthesis of an efferent duct form of SGP-1 that is targeted from the Golgi apparatus to secondary lysosomes after its glycosylation. In order to determine the biosynthetic pathway of SGP-1 within the efferent ducts, an I.V. injection of 35S-cysteine followed by immunoprecipitation and SDS-PAGE revealed that SGP-1 was initially biosynthesized as a 55 kDa protein. This protein appears to be post-translationally modified to a 65 kDa form after 1 hour, which preceded the appearance of the 70 kDa form, and smaller peptides of about 15 kDa characteristic of saposins after 3-4 hours. Western blot analysis of ligated efferent ducts showed an increase in the biosynthesis of the 70 kDa form of SGP-1 when compared to untreated controls, however, it has yet to be established if this protein is secreted or retained in an intracellular compartment.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8430912 TI - Preservation of cardiac myocytes subjected to different preconditions: a comparative morphometric study of beating, fibrillating, and cardioplegically arrested canine hearts. AB - This study compares the ultrastructure of beating canine hearts with that of hearts subjected to different clinically common forms of cardiac arrest. The contraction state per test field was ascertained according to a specially developed classification. The volume density of myofibrils and the surface to volume ratio of mitochondria were used as parameters for cellular and mitochondrial swelling. Contraction bands were not found in any of the differently pretreated hearts. Following immersion fixation, contractions as well as over- and hypercontractions in beating, fibrillating, and St. Thomas-arrested hearts are significantly more pronounced than in HTK-arrested hearts. Cellular and mitochondrial volumes were similar in beating and fibrillating hearts. St. Thomas-perfusion significantly decreased cellular and mitochondrial volume compared to beating hearts, but these values were in the same range as in fibrillating hearts. Only HTK-solution actually led to a strong reduction of these compartments. Compared to immersion, perfusion fixation after coronary perfusion with cardioplegic solutions led to comparable cellular volumes, but significantly elevated the percentage of relaxed sarcomeres and significantly reduced mitochondrial swelling. The best structural preservation of myocytes was found after HTK-perfusion and perfusion fixation. Such ultrastructural quantitative and morphometrical parameters are powerful tools since results confirm that the degree of myocardial preservation depends on the method of cardiac arrest. This forms the basis for the choice of preconditions for subsequent ischemia. Furthermore, significant alterations of myocardial ultrastructure depend on a combination of the functional state of the heart, the method of cardioplegia, and the technique of fixation. PMID- 8430913 TI - Development of the coronary arteries and cardiac veins in the dogfish (Scyliorhinus canicula). AB - The development of the coronary system in the Dogfish was studied using light microscopy. The sample examined consisted of 44 embryos and four newborns. The chronology of events occurring during the process was referred to the total length (TL) of the specimens. The nourishment of the developing myocardium first takes place by means of intertrabecular sinusoids. This system is later switched to a circulation through coronary vessels. The cardiac veins develop earlier than the coronary arteries. The earliest evidence of development of heart vessels in the present sample was the appearance of a diverticulum from the sinus venosus in three embryos of 31 mm TL. This diverticulum outlined the future coronary sinus. Both the atrioventricular and conoventricular venous rings were completely developed in an embryo of 36 mm TL. Coronary artery vessels appeared for the first time in embryos of 40 mm TL. In these specimens, two arteries arose from the midventral hypobranchial artery and divide to give rise to the four coronary artery conal trunks. In a 51-mm TL embryo it was already possible to follow the course of the coronary arteries, from the hypobranchial artery to the conoventricular groove. All main coronary vessels were fully developed in embryos of more than 58 mm TL. However, the arteries supplying the atrium were firstly recorded in a newborn of 77 mm TL. Birth usually occurs when the shark reaches about 72-76 mm TL. PMID- 8430914 TI - Immunolocalization of basal lamina components during development of chick otic and optic primordia. AB - Immunolocalization of laminin, fibronectin, and type IV collagen was examined during early morphogenetic shape changes of the avian inner ear and eye. The ear was studied from formation of the otic placode to invagination of the otic pit and the eye from the optic vesicle stage to formation of an optic cup. Distribution and intensity of immunoreactivity were compared in the two organ primordia and in adjacent epithelial layers. Laminin formed a continuous layer at the basal surface of the otic ectoderm and adjacent neural tube at all stages. The basal surfaces of the optic and lens epithelia also were continuously covered with laminin throughout development. The otic placode became attached to the neural ectoderm through a single layer of fibronectin and collagen IV between the layers of laminin. The ring-like attachment between the edges of the optic cup and lens primordium had the same structure. In addition, the central regions of the optic and lens primordia were attached by fibrils containing type IV collagen, whereas finer strands containing fibronectin and laminin also connected the otic epithelium and neural tube. The results are discussed in terms of models of invagination for the two primordia. PMID- 8430915 TI - Eosinophilic granulopoiesis in human fetal liver. AB - Eosinophilic granulopoiesis was investigated in human fetal liver during intrauterine life from 5 to 34 weeks of gestation. Eosinophilic granulocytes were observable for the first time at 5 weeks in the hepatic laminae and were frequently found in the late embryonic period around the large vessels and in the mesenchyme adjacent to the liver. Eosinophilic granulopoiesis increased gradually in the hepatic laminae (P < 0.01) after 20 weeks of gestation and in the portal areas (P < 0.05) after 16 weeks of gestation. The proportions of each cellular differentiation stage were relatively constant during fetal life, but a greater number of mature eosinophils were observed in the portal areas. Eosinophilic granulopoiesis was evident in all the hepatic tissue components, but developed more actively in portal areas than in hepatic laminae during intrauterine life. Eosinophilic granulopoiesis preceded both erythropoiesis and megakaryopoiesis in the human embryonic liver. Although the latter two occurred mainly in the hepatic laminae, eosinophilic granulopoiesis developed more actively in the portal areas, where it exhibited increasing activity along with the development of the component cells. PMID- 8430916 TI - Scanning electron microscopic observations of human fetal kidney maturing in vivo and in serum-free organ culture. AB - A serum-free model has been developed in our laboratory enabling us to maintain human fetal kidney in culture for periods of 5 days or more. In this totally defined system, morphological integrity of these explants was shown to be preserved at both the light and the electron microscopic levels. The present work was undertaken to validate our culture model via scanning electron microscopy, a technique allowing surface observation of micromorphological features overlooked by conventional microscopy. In uncultured kidney, different developmental stages of nephron formation were identified. A sparse population of short microvilli was present on most cell apical membranes. Cell outlines were polygonal and demarcated by longer and densely packed microvilli. In proximal tubules, these microvilli were in the process of forming a brush border. In the majority of cells, one or two cilia with twisted or hooked tips projected into the capsular space or tubule lumen. Microcraters and bleb-like structures characterized the luminal membrane of many cells. The urinary papilla epithelium was composed of some ciliated principal cells but mostly of intercalated cells with either apical microplicae, microvilli, or both. Micro-projections formed zipper-like intercellular junctions. In culture, ultrastructural features, including membrane pits and spherical vesicles, were similar to those in uncultured explants. In summary, these novel observations in cultured fetal kidney indicate that ultrastructural integrity is well preserved in serum-free medium and that the present model is a valuable tool to study human nephrogenesis. PMID- 8430917 TI - Parenchymal cell proliferation and mechanisms for maintenance of granular duct and acinar cell populations in adult male mouse submandibular gland. AB - To evaluate proliferation as a factor in maintenance of parenchymal cell populations in adult male mouse submandibular glands, a variety of surveys were conducted following a pulse with 3H-thymidine. Striated granular duct (SGD) cells had the highest labeling index, followed by intercalated duct (ID) cells, then acinar (AC) cells, and granular duct (GD) cells had the lowest. These cell types showed from 30% to 60% completion of mitosis by 24 hr, with SGD, AC, and GD showing a likely second wave of mitosis sometime between 2 and 7 days after the pulse. About 40% of the pulse-labeled cells still remained as single cells at 42 days after the pulse. Repeat divisions in daughter cells of the primary labeled cells were very rare. A shift in the pattern of labeled cells at the ID-GD junction indicates that ID and SGD cells in this compartment are differentiating to GD cells. Further comparison of the magnitude of this conversion with the amount of noncompartmental GD cell proliferation provided a basis for calculating that approximately 70% of GD cell population maintenance occurs by self proliferation, and the remaining 30% is contributed by differentiation from ID and SGD cells. A similar survey at the ID-acinus junction showed no evidence of conversion of ID cells to AC cells indicating that most, if not all, proliferative activity leading to AC cell population maintenance occurs by self proliferation. Finally, based in part on structural changes at the ID-GD junction during the survey period, a pattern of cell conversion described as "in situ differentiation" is proposed. When this pattern is carried to fruition, this explains several structural features of the secretory complex typical to the male pattern submandibular gland. The proposed mechanism is supported by a three dimensionally reconstructed sequence of likely intermediate structures. PMID- 8430918 TI - Thymoma and chronic illness. PMID- 8430919 TI - Preventive effect and duration of action of disodium cromoglycate and procaterol on exercise-induced asthma in asthmatic children. AB - We evaluated the preventive effect and duration of action of disodium cromoglycate (DSCG) and procaterol nebulizer solutions on exercise-induced asthma (EIA) in 14 asthmatic patients. Disodium cromoglycate solution prevented EIA one hour after inhalation in 11 out of 14 (78.6%), and in some patients after four (36.5%) and eight hours (15.4%). The preventive effect and duration of action of DSCG depended on the severity of EIA in each subject. Procaterol solution had a greater effect than DSCG at any time point in the study. With both drugs, however, the effect decreased four and eight hours after inhaling and was related to the severity of the EIA. PMID- 8430920 TI - Dose ranging study: cetirizine in the treatment of atopic dermatitis in adults. AB - One hundred seventy-eight adults with atopic dermatitis were included in this double-blind, parallel, randomized study where the effects of placebo, and cetirizine, 10, 20, and 40 mg administered daily during 4 weeks were measured. Local rescue therapy, which consisted of emollients and 1% hydrocortisone, was permitted and patients in all four groups used it in the same regular way. Severity of atopic dermatitis was measured via the following parameters: pruritus (visual analog scales used by both the investigator and patients), four point scale (absent, slight, moderate and serious) symptom scores for erythema, vesicles, excoriation, and lichenification in 14 body areas and a final visit assessment of the patient's general condition. The patient's quality of sleep was also measured along with standard blood chemistry tests. Adverse events during the study were recorded as well. In total 127 patients were assessed for efficacy. A statistically significant (P < or = .05) improvement was observed in all therapeutic groups for the following parameters: erythema, excoriation, lichenification, total symptom score, area involved, and pruritus. Cetirizine showed a dose-related improvement in the following parameters measured: erythema, lichenification, total symptom score, area involved, final assessment, and pruritus (measured by the patient at each visit). At 40 mg, cetirizine was significantly (P < or = .05) more effective than placebo for these parameters. At 20 mg, this was true only for pruritus (measured by the patient at each visit).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430921 TI - Behavioral and cognitive effect of theophylline: a dose-response study. AB - The behavioral and cognitive effects of theophylline were studied in 14 asymptomatic asthmatic children. A double-blind crossover design was used with two dosage levels. Conners parent ratings suggest behavioral improvement by the second week of treatment, regardless of dosage or order of administration. No effects were found on cognitive measures. We conclude that the majority of behavior problems associated with theophylline occur during the induction phase, and that for most children behavior and attention problems rapidly return to baseline or improve. PMID- 8430922 TI - Pneumocystis carinii pneumonia presenting as asthma: increased bronchial hyperresponsiveness in Pneumocystis carinii pneumonia. AB - Two male patients presented with clinical and laboratory findings consistent with typical bronchial asthma and subsequently developed Pneumocystis carinii pneumonia (PCP). Only on subsequent questioning did both admit to homosexuality and behavior associated with a high risk of HIV-infection. In order to determine how frequently reversible airway obstruction is seen in patients with PCP, we measured peak expiratory flow rates (PEFR) before and after bronchodilator administration in 37 of these patients. Initial PEFR measurements revealed a significant decrease in PEFR (< 80% predicted) in 84%, with 54% of these exhibiting a significant bronchodilator response (> or = 15% increase). For comparison, peak flow measurements were made in a control group of 31 HIV infected patients without acute PCP, divided between those with asymptomatic HIV infection, AIDS-related complex (ARC), and AIDS, (including patients with previous PCP). Only 23% of these individuals had low PEFR, and only 3% exhibited bronchodilator responses. In order to confirm the existence of bronchial hyperreactivity in patients with PCP, another 16 patients with PCP were tested by methacholine bronchial challenge and 50% were found to have positive responses. These findings suggest that both reversible airway obstruction and airway hyperreactivity are found in association with acute PCP and that as a result some patients with PCP may present with symptoms of asthma. It is important for physicians to have a high degree of suspicion to avoid missing a diagnosis of PCP in a patient presenting with apparent asthma. PMID- 8430923 TI - Double-blind trial of pyridoxine (vitamin B6) in the treatment of steroid dependent asthma. AB - Pyridoxine has been reported to largely correct an abnormality of tryptophan metabolism present in patients with bronchial asthma and to reduce the symptoms of asthma in long-term studies. We enrolled 31 patients requiring steroids (oral or inhaled) for the treatment of their asthma in a double-blind, placebo controlled assessment of 9 weeks' treatment with pyridoxine 300 mg per day (13) or placebo (18). Outcome variables included PEFR, FEV1, asthma symptom scores, 24 hour urinary 5-HIAA, skin test reactivity to histamine and compound 48/80 and blood serotonin levels. Plasma pyridoxine levels indicated overall patient compliance with a mean change from baseline to the end of the study of 82.5 +/- 27.7 ng/mL in patients on pyridoxine and -2.9 +/- 10.3 for those on placebo (P = .0001). Furthermore, patients routinely treated with theophylline had lower (10 +/- 8 ng/mL) plasma pyridoxine levels at baseline than those not on it (19 +/- 6 ng/mL; P = .01), suggesting that theophylline may lower plasma pyridoxine levels. There was no significant difference between the pyridoxine and placebo groups in the change from baseline to the last 2 weeks of treatment phase in any of the outcome variables. We conclude that under the conditions of the study, treatment with oral pyridoxine failed to improve the outcome variables in patients requiring steroids for the treatment of their asthma. The results of this study suggest that prescription or usage of oral pyridoxine for the treatment of asthma cannot be justified in such patients. PMID- 8430924 TI - Effect of inhaled beclomethasone dipropionate on bronchial responsiveness in patients with asthma. AB - We investigated the effect of 300 micrograms of inhaled beclomethasone dipropionate (BDP) daily on bronchial responsiveness to methacholine and pulmonary function of 22 subjects with asthma in a single-blind, crossover study. The severity of bronchial hyperresponsiveness lessened significantly during treatment with BDP (P < .01). No significant changes occurred in FEV1 or in the control value of airway conductance. We conclude that a 300-micrograms total daily dose of BDP is an efficacious treatment for patients with asthma. Because suppression of adrenal function and systemic adverse effects can occur in asthmatic patients treated with inhaled corticosteroids, especially children, long-term treatment with inhaled steroids should employ minimal daily doses necessary. PMID- 8430925 TI - Prolonged bronchodilating effect of formoterol versus procaterol in bronchial asthma. AB - The tolerability and the duration of effect of 12 micrograms of formoterol and 25 micrograms of procaterol administered via metered-dose aerosol to 12 stable asthmatic patients were evaluated in a double-blind, placebo controlled trial. FEV1, pulse rate, and blood pressure were measured at baseline and every two hours after dosing for 12 hours. The bronchodilation peak was observed after two hours for both drugs. Formoterol induced a significant bronchodilating effect for 12 hours compared with both baseline and placebo values. With procaterol, significant bronchodilation occurred for six hours compared with baseline values and four hours compared with placebo. No significant changes were observed in pulse rate and blood pressure with either drug. Four subjects complained of muscle tremor after procaterol administration. We conclude that in subjects with stable asthma, inhaled formoterol at a dose of 12 micrograms maintains significant bronchodilation for 12 hours after dosing and is very well tolerated. Further studies are required to evaluate effectiveness and tolerability of high dose formoterol treatment in acute severe asthma therapy. PMID- 8430926 TI - Cell content and albumin concentration in nasal lavage from patients with rhinitis. AB - Influx of inflammatory cells in the nose was evaluated in 14 patients with rhinitis and 11 healthy subjects. Nasal secretions were obtained by nasal lavages. Total cell count and differential count were carried out with a Neubauer chamber and in cytospin slides, respectively. Cells were classified according to their morphology as epithelial cells without nuclei (degenerated), epithelial nucleated cells, neutrophils, eosinophils, and other. Total protein and albumin concentration were measured by the Lowry method and a nephelometric assay respectively. A statistically significant difference was found in total nucleated epithelial cells (P < .01), total neutrophils (P < .01), and total eosinophils (P < .05) between patients and healthy subjects. A significant correlation was found between albumin/total protein concentration with eosinophil numbers (r = .83, P < .001) in patients with rhinitis. These findings suggest that eosinophils participate in the inflammatory process taking place in rhinitis. Since the cellularity present in the nose of rhinitic patients is similar to that usually found in the bronchial secretions of asthmatic patients obtained by bronchoalveolar lavage, our results also suggest that nasal lavage may be used in the study of the inflammatory cells involved in airway diseases. PMID- 8430927 TI - Cimetidine prevents erythema multiforme. PMID- 8430928 TI - Selection of allergens for skin testing. PMID- 8430929 TI - Differential diagnosis of ocular allergic disorders. PMID- 8430930 TI - Biomechanical study of the effect of coxofemoral positioning on passive hip joint laxity in dogs. AB - Ten coxofemoral joints from 5 dog cadavers were used to study the effect of coxofemoral positioning on passive hip laxity. A material test system was used to measure lateral translation when force was between 20 N of compression and 40 N of distraction. Using the orthogonal coordinate system imposed in this study, neutral position was empirically defined at 15 degrees of extension and 10 degrees of abduction, relative to the plane of the pelvis, and no internal or external rotation of the femur. The hips were mounted in a custom-designed jig that allowed 1 rotational degree of freedom (ie, either flexion/extension, adduction/abduction, or internal/external rotation), while holding the other 2 constant. Lateral translation of the hips was tested at 10 degrees intervals from 30 degrees of flexion to 70 degrees of extension, 40 degrees of adduction to 60 degrees of abduction, and 30 degrees of internal rotation to 40 degrees of external rotation. Lateral displacement was maximal at 10 degrees of extension, 20 degrees of abduction, and 10 degrees of external rotation, approximating the neutral coxofemoral position during stance. As the hips were rotated into extreme positions, the amount of lateral displacement occurring with the same applied load decreased significantly to 32.0 to 65.3% of the maximal displacement. Determining the position of the hip associated with maximal passive laxity in vitro is essential to the design of a precise and accurate clinical stress radiographic method to quantitate joint laxity in dogs. Our results confirm earlier work that passive hip joint laxity is at a maximum with the hip approximately in a neutral weight-bearing position. PMID- 8430931 TI - Comparison of stressed simultaneous urethral pressure profiles between anesthetized continent and incontinent bitches with urethral sphincter mechanism incompetence. AB - The popular urodynamic technique of stressed urethral pressure profilometry used for investigation of genuine stress incontinence in women was adapted and applied to bitches. The aim was to assess the suitability and reproducibility of the technique in the canine species, and to determine whether differences seen in continent and incontinent women were found in bitches. Resting and stressed simultaneous urethral pressure profiles were obtained for 25 continent and 25 incontinent bitches, the latter diagnosed as having urethral sphincter mechanism incompetence. The stressed urethral pressure profiles were produced by ballottement of the abdomen during catheter withdrawal. The degree of stress induced was consistent and had got short-term reproducibility. Highly significant (P < 0.001) differences in the percentage of negative spikes extending below the resting intravesical pressure were found between continent and incontinent bitches. Significant differences were not observed in the pressure transmission profiles between continent and incontinent bitches; both groups had a gradual decrease in pressure transmission from the bladder neck to the external urethral orifice. The distance from the start of the urethral pressure profile to the first negative peak (attributable to respiration or ballottement) on the subtracted profile was compared with the radiographic distance that the bladder neck was positioned with respect to the cranial pubic brim, taking body weight and continence status into account. Body weight and continence status did not have significant effect on the relation in either instance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430932 TI - Isolation of feline eosinophils via peritoneal lavage. AB - Fourteen cats were inoculated orally with 1 of 2 infective doses of Toxocara canis to induce eosinophilia. Cats were subsequently challenge exposed twice via intraperitoneal injection with 1 of 2 T canis antigen preparations. Peritoneal lavage was performed 2 days after antigenic challenge exposure, and eosinophils in the peritoneal lavage fluid were quantified. None of the cats developed clinical signs of disease after infection. All cats developed peripheral eosinophilia after infection. Significant (P < 0.05) difference in mean eosinophil count from the lavage fluid was observed between lavage 1 (prechallenge exposure) and lavages 2 and 3 (postchallenge exposure) in both groups of cats. Significant difference in eosinophil count was not found between cats given different doses of eggs. After initial challenge exposure, significantly (P < 0.05) more eosinophils were obtained from cats given antigen preparation 2 (prep-2) than from those given antigen prep-1. This difference was no longer observed after the second challenge exposure with higher doses of either antigen prep-1 or prep-2. In cats given antigen prep-2, significant difference was not found between lavages 2 and 3. However, in cats given antigen prep-1, eosinophil count was significantly (P = 0.005) greater in fluid obtained from lavage 3, compared with eosinophil count from lavage 2. Mean +/- SEM percentage of eosinophils in the fluid from lavage 3 in all cats was 70.8 +/- 2.2%. Other cell types included macrophages, neutrophils, lymphocytes, and mast cells. Gross postmortem findings were mild. One- to 3-mm nodular white foci of inflammation were observed on the serosal surfaces of the liver, spleen, kidneys, and omentum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430933 TI - Corneal thickness measured by ultrasonic pachymetry in cats. AB - Ultrasonic pachymetry was used to measure central, superior peripheral, and temporal peripheral corneal thickness of 35 cats (70 eyes) with normal corneas, anterior chambers, and intraocular pressures. Mean central corneal thickness for both eyes in 3 locations for 35 cats was 578 +/- 64 microns. Significant differences did not exist between central and peripheral corneal thickness. Corneal thickness increased significantly (P < 0.0001) with age up to 100 months. There was no significant difference in corneal thickness with regard to sex of the cats when adjusted for age. PMID- 8430934 TI - Total and differential leukocyte counts, N-acetyl-beta-D-glucosaminidase activity, and serum albumin content in foremilk and residual milk during endotoxin-induced mastitis in cows. AB - Foremilk, residual milk, and blood samples were studied for 10 days during acute mastitis episodes induced by endotoxin infused via the teat canal. Quarter milk and blood samples were collected frequently for 3 days after the infusion and thereafter once or twice daily. Leukocyte concentration in milk and blood was determined by flow cytometry. Within 2 hours after infusion of the endotoxin, clinical mastitis was observed. Total leukocyte concentration and proportion of neutrophils increased significantly (P < 0.05) by postinfusion hour (PIH) 2 in foremilk and by PIH 4 in residual milk. From PIH 2, serum albumin content and N acetyl-beta-D-glucosaminidase activity were significantly increased in both fractions. Neutrophils were the predominant leukocyte population in both fractions until PIH 59. From PIH 72, lymphocytes were the predominant cell population until PIH 175 in foremilk and until PIH 223 in residual milk. Serum albumin content and N-acetyl-beta-D-glucosaminidase activity in residual milk was significantly lower than in foremilk from PIH 4 to 24 and from PIH 24 to 59, respectively. Regarding total and differential leukocyte counts, values for the 2 fractions followed the same pattern throughout the course of inflammation, probably owing to frequent sample collection. Total and differential cell counts tended to differ between the fractions during some periods, although differences were not statistically significant. When samples were taken less frequently, the total leukocyte concentration in residual milk was higher than that in foremilk. Although sample collections were frequent, clustering of immature neutrophils was not observed in the cytofluorogram of blood leukocytes in this study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430935 TI - Measurement of ragweed-specific IgE in canine serum by use of enzyme-linked immunosorbent assays, containing polyclonal and monoclonal antibodies. AB - Using polyclonal rabbit and monoclonal mouse anti-dog IgE antibodies, we developed ELISA for measurement of ragweed-specific IgE in canine serum. In the ELISA, microtitration plates were coated with ragweed extract and sequentially incubated with canine serum, purified monoclonal or polyclonal anti-dog IgE, and conjugated goat antibody to mouse IgG or rabbit IgG. Serum ragweed-specific IgE values were measured by the 2 ELISA in serum samples from 60 ragweed-allergic dogs and in serum from 10 control dogs. Passive cutaneous anaphylaxis (PCA) tests were performed on these sera to compare results with those of the ELISA. Mean coefficient of variation between assays was 0.20 +/- 0.10 for the assay using the polyclonal antibody and was 0.17 +/- 0.10 for that using monoclonal antibody. Sensitivity was 0.6 U/ml for the ELISA, using polyclonal antibody, and 2.5 U/ml for the ELISA, using monoclonal antibody. Serum ragweed-specific IgE values measured by the 2 ELISA strongly correlated with PCA titers (P < 0.0000), but the ELISA using polyclonal antibody had higher correlation with PCA titer (r = 0.84) than the ELISA using monoclonal antibody (r = 0.59). The geometric mean ragweed specific IgE value measured by the 2 ELISA and by PCA testing, was significantly higher (P < 0.0000). in allergic dogs than in control dogs. The 2 ELISA were specific, sensitive, and reproducible for measurement of ragweed-specific IgE in canine serum. PMID- 8430936 TI - Factors influencing fecal shedding of Campylobacter jejuni in dogs without diarrhea. AB - Rectal swab specimens were collected from 362 apparently healthy dogs of different origin, age, breed, and sex. Specimens were obtained in summer, autumn, and winter. Ninety-five thermophilic Campylobacter spp were isolated: C jejuni biotype I, n = 57, C jejuni biotype II, n = 1, C coli, n = 36, and C laridis, n = 1. Biotypes of C jejuni recovered were the same as those associated with Campylobacter-induced enteritis in human beings. Prevalence of C jejuni was significantly (P < 0.05) greater: in dogs < 6 months old than in adult dogs; in dogs living under high density and cohabitation housing conditions for long periods; and in autumn. PMID- 8430937 TI - Persistence of tissue cysts in edible tissues of cattle fed Toxoplasma gondii oocysts. AB - Four 1-year-old steers were each inoculated orally with 10,000 Toxoplasma gondii oocysts of the GT-1 strain and euthanatized on postinoculation days (PID) 350, 539, 1191, and 1201. Samples (500 g) of tongue, heart, semimembranosus and semitendinosus muscles (roast), intercostal muscles (ribs), longismus muscles (tenderloin), brain, kidneys, liver, and small intestine were bioassayed for T gondii by feeding to cats and examination of cat feces for shedding of oocysts. Toxoplasma gondii was recovered by bioassays in cats for the 3 steers necropsied PID 350, 539, and 1191, but not from the steer euthanatized on PID 1201. Cats shed oocysts after ingesting tongue from 2 steers, heart from 3 steers, liver from 2 steers, and roast, ribs, brain, and intestines from 1 steer each. Toxoplasma gondii was not isolated from any of the other bovine tissues. In addition to tissues bioassayed in cats, homogenates of mesenteric lymph nodes, lungs, spinal cord, spleen, and eyes were bioassayed in mice for T gondii infection. Toxoplasma gondii was not recovered from the 135 mice inoculated with tissue from each of the 4 steers. All 4 inoculated steers developed high T gondii antibody titers (> or = 1:8,000) in the agglutination test, using formalin-fixed whole tachyzoites. In the steer euthanatized on PID 1201, agglutinating T gondii antibody titers decreased from 1:4,000 to 1:320 between 2 and 5 months after inoculation and to 1:20 by 19 months after inoculation. PMID- 8430938 TI - Cardiovascular responses to exogenous platelet-activating factor (PAF) in anesthetized ponies, and the effects of a PAF antagonist, WEB 2086. AB - The effects of exogenous platelet-activating factor (PAF) were determined in anesthetized ponies. Administration of PAF induced a decrease in cardiac index that resulted in systemic hypotension. This was followed by tachycardia, hypertension, and a return of cardiac index to baseline. Pulmonary arterial pressure increased markedly because of pulmonary vasoconstriction. Exogenous PAF also caused leukopenia and thrombocytopenia. The specific PAF receptor antagonist (WEB 2086) blocked all PAF-induced changes. Flunixin meglumine, a cyclooxygenase inhibitor, abolished the pulmonary hypertension and tachycardia, and attenuated the systemic hypotension but did not change the PAF-induced peripheral cellular changes. The PAF antagonist also inhibited platelet aggregation induced by PAF in vitro. The PAF-induced changes are similar to those reported after endotoxin exposure in horses. PMID- 8430939 TI - Effect of topically applied demecarium bromide and echothiophate iodide on intraocular pressure and pupil size in beagles with normotensive eyes and beagles with inherited glaucoma. AB - Topically applied demecarium bromide (0.125 and 0.25%) and echothiophate iodide (0.125 and 0.25%) solutions were evaluated in Beagles with normotensive eyes and Beagles with inherited glaucoma. In single-dose studies, the effects of intraocular pressure (IOP) and pupil size (PS) were measured in eyes before drug treatment and in drug- and nondrug-treated eyes. Both concentrations of the 2 drugs induced long-term miosis and decrease in IOP in normotensive eyes of Beagles and of eyes of Beagles with inherited glaucoma. Demecarium bromide (0.125 and 0.5%) decreased IOP for 49 and 55 hours, respectively. Echothiophate iodide (0.125 and 0.5%) reduced IOP for 25 and 53 hours, respectively. The miosis associated with both concentrations of the 2 drugs generally paralleled the decreases in IOP. PMID- 8430940 TI - Inhibition of lipopolysaccharide-induced macrophage tumor necrosis factor-alpha synthesis by polymyxin B sulfate. AB - The antibiotic polymyxin B sulfate is a cationic polypeptide with a unique cyclical configuration and distinct cationic characteristics. In this investigation, polymyxin B was evaluated to determine its ability to prevent synthesis of lactic acid and tumor necrosis factor-alpha (TNF-alpha) by lipopolysaccharide-stimulated strain RAW 264.7 macrophage-like cell populations. In this context, gradient concentrations of polymyxin B were formulated in the presence of fixed concentrations of lipopolysaccharide fractions from Escherichia coli (B4:0111), E coli (J5), Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella minnesota, and S typhimurium (Re). Quantitation of TNF-alpha was established by the application of a tissue culture-based biological assay system, using the WEHI 164 clone 13 indicator cell line. Investigations also included evaluation of the ability of gradient concentrations of lipopolysaccharide fractions from E coli (B4:0111), E coli (J5), K pneumoniae, P aeruginosa, S minnesota, and S typhimurium (Re) to form a complex with polymyxin B. This was established through application of high-performance thin-layer chromatography techniques. On the basis of the known molecular characteristics of lipopolysaccharide, its lipid A-core subfractions, and polymyxin B, these results imply that cytoprotective properties of polymyxin B are attributable to direct interaction and subsequent complex formation. More specifically, the mechanism by which polymyxin B exerts affinity for lipopolysaccharide fractions is proposed to occur through attractive ionic interactions established between the cationic diaminobutyric acid residues of polymyxin B and the mono- or diphosphate group(s) of the lipid A-core moiety. It is highly probable that this molecular phenomenon is accompanied by hydrophobic interactions established between the terminal methyloctanoyl or methylheptanoyl groups of polymyxin B and the saturated carbon chains of the lipid A-core subfraction of lipopolysaccharide fractions. PMID- 8430941 TI - Effect of hypercapnia on the arrhythmogenic dose of epinephrine in horses anesthetized with guaifenesin, thiamylal sodium, and halothane. AB - The effect of hypercapnia on the arrhythmogenic dose of epinephrine (ADE) was investigated in 14 horses. Anesthesia was induced with guaifenesin and thiamylal sodium and was maintained at an endtidal halothane concentration between 0.86 and 0.92%. Base-apex ECG, cardiac output, and facial artery blood pressure were measured and recorded. The ADE was determined at normocapnia (arterial partial pressure of carbon dioxide [PaCO2] = 35 to 45 mm of Hg), at hypercapnia (PaCO2 = 70 to 80 mm of Hg), and after return to normocapnia. Epinephrine was infused at arithmetically spaced increasing rates (initial rate = 0.25 micrograms/kg of body weight/min) for a maximum of 10 minutes. The ADE was defined as the lowest epinephrine infusion rate, to the nearest 0.25 micrograms/kg/min, at which 4 premature ventricular complexes occurred in a 15-second period. The ADE (mean +/- SD) during hypercapnia (1.04 +/- 0.23 micrograms/kg/min) was significantly (P < 0.05) less than the ADE at normocapnia (1.35 +/- 0.38 micrograms/kg/min), whereas the ADE after return to normocapnia (1.17 +/- 0.22 micrograms/kg/min) was not significantly different from those during normocapnia or hypercapnia. Baseline systolic and diastolic arterial pressures and cardiac output decreased after return to normocapnia. Significant differences were not found in arterial partial pressure of O2 (PaO2) or in base excess during the experiment. Two horses developed ventricular fibrillation and died during normocapnic determinations of ADE. Hypercapnia was associated with an increased risk of developing ventricular arrhythmias in horses anesthetized with guaifenesin, thiamylal sodium, and halothane. PMID- 8430942 TI - Differential study of electrocardiographic intervals in two neonatal crossbred swine. AB - The influence of the QT, TQ, and ST intervals, and heart score on both cardiac cycle duration (RR) and diastole/systole (D/S) quotient were analyzed during the neonatal (1 day and 5 days) pigs belonging to 2 crossbreeds of different rusticity, Landrace x Belgian White (LBW) and Landrace x Duroc Jersey (LDJ). Our findings indicate that the shortening of the RR interval in 5-day-old pigs of both crossbreeds was determined by different variables in each breed. In LDJ pigs, this shortening was only associated with a shortening of ventricular activation, and in each age group, the systole and the diastole contributed equally to the RR value. The D/S quotient did not differ significantly in 1-day old vs 5-day-old pigs, and at both ages, the quotient was only determined by the TQ value. In LBW pigs, the RR, QT, TQ, and ST were shortened, but only the shortening of QT was significant as a result of an acceleration of the ventricular recuperation process. Moreover, differences were found between 1-day old vs 5-day-old pigs with regard to the contribution of the different intervals to the RR duration. In 1-day-old pigs, the RR depended closely on the TQ, whereas in 5-day-old pigs, all intervals contributed significantly to its duration. The D/S quotient was not significantly different in 1-day-old vs 5-day-old pigs, but a different contribution of the variables studied was observed at the 2 ages selected. In 1-day-old pigs, D/S quotient depended on the diastole duration, whereas in 5-day-old pigs, the diastole and systole contributed to its variation. PMID- 8430943 TI - Characterization of cardiac alterations in nonsedated cynomolgus monkeys. AB - Spontaneous variations in ECG and continuous Holter monitor recordings of a colony of 31 male and 31 female cynomolgus monkeys were characterized. Electrocardiograms recorded for approximately 1 minute on 2 occasions in nonsedated monkeys were analyzed, and intervals (PR, QRS, and QT), amplitudes (P, Q, R, and T), and heart rate were determined from lead II of these tracings. In addition, Holter monitor recorders were placed on monkeys by use of carrying jackets for 16 to 24 hours of continuous recording twice during the study, and tapes were analyzed. Mean heart rate and intervals and amplitudes were similar for males and females on the first and the second recordings. Mean heart rate for males and females was 232 and 226 beats/min (bpm), respectively. The PR, QRS, and QT interval measurements, 77, 29, and 165 milliseconds, respectively, were recorded for males and 81, 30, and 162 milliseconds, respectively, were recorded for females. The P, Q, R, and T wave amplitudes were 0.16, 0.11, 0.64, and 0.28, mV respectively, for males and were 0.17, 0.10, 0.79 and 0.24 mV, respectively, for females. In addition, ventricular ectopic beats were observed in ECG from 5 females, but not in ECG from the males. Single ventricular ectopic beats were observed in 3 females for either the first or second tracing. One monkey had ectopic beats in both tracings, but in both instances, the number of ectopic beats was low (3 singles in the first and 1 in the second tracing).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430944 TI - Changes in fluid composition on the serosal surface of jejunum and small colon subjected to venous strangulation obstruction in ponies. AB - In 6 anesthetized ponies, 3 segments of jejunum and 3 segments of small colon were isolated from the peritoneal cavity in plastic bags filled with Hanks' balanced salt solution. One jejunal and 1 small colon segment were subjected to venous strangulation obstruction for 3 hours (VSO-3), venous strangulation obstruction for 6 hours (VSO-6), or a 6-hour sham procedure to control for changes induced by isolation in a plastic bag. Additional segments of jejunum and colon that were not placed in bags served as controls for histologic examination and collagenase measurements. Samples of fluid surrounding the intestine were obtained for chemical analyses, nucleated cell count, aerobic and anaerobic bacteriologic culture, and measurement of collagenase activity. Full-thickness tissue samples were obtained for histologic examination and measurement of collagenase content. Bacteria did not cross the intestinal wall after 3 and 6 hours of VSO, despite severe mucosal lesions in these segments. At 6 hours, PO2 was significantly less and PCO2 was significantly (P < 0.05) greater in the fluid surrounding the VSO-6 jejunal segments, compared with the sham jejunal segments. The pH was significantly (P < 0.05) less in fluid surrounding VSO-6 small colon segments, compared with the sham colon segments at 6 hours. For jejunum and small colon, phosphate and lactate concentrations were significantly (P < 0.05) greater in VSO-6 fluid than in the corresponding sham fluids at 6 hours. Fibrin formed around all VSO segments, although fibrinogen was not detected in the surrounding fluid, indicating possible rapid conversion of fibrinogen to fibrin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430945 TI - Temporal matrix synthesis and histologic features of a chondrocyte-laden porous collagen cartilage analogue. AB - Cartilage resurfacing by chondrocyte transplantation, using porous collagen matrices as a vehicle to secure the cells in cartilage defects, has been used experimentally in animals. This in vitro study evaluated the temporal morphologic features and proteoglycan synthesis of chondrocyte-laden collagen matrices. Forty two porous collagen disks were implanted with a minimum of 6 x 10(6) viable chondrocytes, covered by a polymerized collagen gel layer, and 6 disks were harvested after 0, 3, 7, 10, 14, 18, or 22 days of incubation in supplemented Ham's F12 medium at 37 C and 5% CO2. Histologic and histochemical evaluation of formalin-fixed segments of the cultured disks indicated that the chondrocytes proliferated in the implant, producing small groups and linear segments of cells by day 14. The collagen framework remained intact over the course of the study with thick areas attributable to depositions of matrix material after day 10. Alcian blue-stained matrix was evident in the pericellular region of chondrocytes in sections of disks harvested on days 14, 18, and 22. Glycosaminoglycan (GAG) assay by dimethylmethylene blue dye binding after papain digestion of the disk segments revealed negligible amounts of GAG at day 0. Significant (P < or = 0.0001) increase in total GAG content was observed by day 3 (0.329 micrograms/mg of disk) and further increases were observed until a plateau in GAG quantity was seen on day 14. Mean peak GAG content was 0.553 +/- 0.062 micrograms/mg. Secondary treatment of the papain-digested implants with keratanase and chondroitinase ABC yielded similar trends in chondroitin sulfate (CS) and keratan sulfate (KS) concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430946 TI - From the mouths of babes.... PMID- 8430947 TI - Inspiratory pressures with CO2 stimulation and weaning from mechanical ventilation in children. AB - Maximal transdiaphragmatic (Pdimax) and airway occlusion pressures (PaOmax) have been used to predict weaning from mechanical assisted ventilation in adults, but criteria for weaning are still based on trial and error in infants and young children. Because infants and young children cannot cooperate, crying Pdi and PaOmax against an occlusion have been used, but these may not yield maximal values. We hypothesized that breathing CO2 would achieve better Pdimax and PaOmax values by maximizing respiratory drive and help in establishing weaning criteria. To test this, we measured tidal breathing and occluded Pdi and PaOmax in 27 patients (mean age, 15.0 +/- 31.5 SD months) who required prolonged assisted mechanical ventilation and had failed previous weaning attempts. Measurements were performed while patients were breathing spontaneously 100% O2 and 5% and 7% CO2 in O2. The patients achieved higher Pdimax breathing 5% CO2 (73.2 +/- 24.4 cm H2O) than in O2 (61.6 +/- 24.4 cm H2O; p < 0.0001) or in 7% CO2 (69.1 +/- 23.4 cm H2O; p < 0.0001). They also achieved higher PaOmax in 5% CO2 (81.7 +/- 23.5 cm H2O) than with the other gases (69.9 +/- 25.5 in O2, and 77.5 +/- 24.1 in 7% CO2; p < 0.001); 19 patients (70%) were weaned from assisted ventilation within 3.2 +/ 1.9 wk. In 5% CO2, all patients who were weaned achieved Pdimax > 60 cm H2O and could sustain > 60% Pdimax for more than five successive occluded breaths (100% sensitivity; 100% specificity; p < 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430948 TI - Postischemic hypoperfusion during unilateral lung reperfusion in vivo. AB - The incomplete restoration of blood flow during reperfusion may amplify injury by prolonging ischemia; this "no-reflow" has been studied extensively in systemic organs. Our goal was to examine lung blood flow and microvascular function, specifically to determine whether blood flow is altered during lung reperfusion injury in vivo. In a unilateral lung model of ischemia-reperfusion in awake sheep, we measured pulmonary vascular resistance in each lung by radiolabeled microspheres. Measurements were made before 14 h of ischemia and again 4 h after reperfusion. Vascular resistance in the reperfused lung increased 3-fold (9.64 +/ 0.85 to 27.04 +/- 4.73 cm H2O/L/min) during reperfusion. The increase in vascular resistance in the reperfused lung fully accounted for the small increase in overall pulmonary vascular resistance (4.04 +/- 0.26 to 5.52 +/- 0.70 cm H2O/L/min). Microvascular permeability in the reperfused lung increased 52% more than in the contralateral lung, measured by an improved indicator dilution method with additional markers sensitive to surface area (butanediol). We conclude that changes in vascular resistance and microvascular function occur during lung reperfusion injury in vivo. The demonstration that postischemic hypoperfusion occurs during lung reperfusion in vivo suggests possible new avenues of approach to related clinical disorders. PMID- 8430949 TI - The role of endothelium in hypoxic constriction of human pulmonary artery rings. AB - The aim of the study was to elucidate the mechanism of the contraction produced by hypoxia in human intrapulmonary artery rings. Hypoxia (5 mm Hg) produced a contraction that was greater when the artery rings were precontracted (with endothelin-1) than when recorded under optimal resting force. The contraction was similar in small-diameter (0.38 to 0.68 mm) and in large-diameter (2.2 to 4.5 mm) artery rings under resting force. Removal of the endothelium markedly reduced or abolished the hypoxic contraction in precontracted artery rings (large diameter, 26 +/- 9 to -7 +/- 4 g cm-2) or under optimal resting force. Hypoxia markedly reduced or abolished the acetylcholine-induced relaxation in precontracted artery rings without affecting relaxation produced by sodium nitroprusside. Flurbiprofen caused a slight contraction itself (large diameter, 10 +/- 3 g cm-2) and significantly inhibited the contraction produced by hypoxia both under resting force (8 +/- 2 to 2 +/- 1 g cm-2) and in precontracted artery rings (18 +/- 2 to 1 +/- 1 g cm-2). Verapamil had no significant effect on the hypoxic contraction either under resting force or when precontracted. It is concluded that hypoxic contraction of human pulmonary artery rings depends on the presence of endothelium and is partly due to inhibition of a vasodilator cyclooxygenase product. PMID- 8430950 TI - Elevated release of tumor necrosis factor-alpha and interferon-gamma by bronchoalveolar leukocytes from patients with bronchial asthma. AB - Bronchoalveolar lavage (BAL) leukocyte-secreted cytokines are considered to be important mediators of the inflammatory and allergic reactions in the lung. This study examines quantitative changes in the level of tumor necrosis factor-alpha (TNF alpha) and interferon-gamma (IFN gamma) production in BAL cell cultures derived from patients (n = 11) with bronchial asthma. The secretion of TNF alpha and IFN gamma was determined in intact (unstimulated) and phytohemagglutinin/phorbol myristate acetate (PHA + PMA)-stimulated BAL leukocyte cultures and compared with that in control cultures. In all patients studied, the background and PHA + PMA-induced secretion of TNF alpha and IFN gamma was significantly (p < 0.001) higher than that in parallel control cultures. In contrast to BAL cell preparations, the capacity of TNF alpha and IFN gamma secretion by patients' peripheral blood mononuclear cells (PBMC) did not differ from that of control subjects. High spontaneous release of TNF alpha and IFN gamma by patients' BAL leukocytes, but not PBMC, suggest that in the pathophysiology of bronchial asthma, these cytokines may act as local pathogenic agents in the lung. PMID- 8430951 TI - Bronchial reactivity, lung function, and serum immunoglobulin E in smoking discordant monozygotic twins. AB - Smokers with chronic bronchitis and/or chronic obstructive pulmonary disease (COPD) have been reported to have an increased bronchial reactivity (BR). It has been discussed whether increased BR is a risk factor for the development of COPD in smokers. We studied 10 monozygotic twin pairs who were discordant for tobacco smoking by means of histamine provocation tests, lung function tests, and serum samples for total IgE. The smokers had a mild obstructive ventilatory impairment, with FEV1 significantly lower than that of the partner both when it was determined from the flow-volume loops (3.2 +/- 1.0 L for smokers and 3.4 +/- 0.8 L for nonsmokers) and by the Vitalograph spirometer (3.5 +/- 1.0 L for smokers and 3.8 +/- 0.8 L for nonsmokers). Forced midexpiratory flow (FEF25-75%) and forced expiratory flow at 75 to 85% of vital capacity (FEF75-85%) were both significantly lower in the smokers (p < 0.05). The alveolar plateau phase N2 delta test and lung clearing index in the multibreath nitrogen washout test were both significantly affected in the smokers (p < 0.05 and p < 0.01, respectively). We found no significant difference in histamine reactivity between smokers and nonsmokers and no correlation between differences in reactivity and differences in lung function within pairs. Total serum IgE was significantly higher in the smokers than in their nonsmoking siblings. These data suggest that obstructive ventilatory impairment and raised serum IgE are earlier and more constant manifestations of tobacco smoking than increased bronchial reactivity. Thus, bronchial hyperreactivity does not seem to be a major risk factor for the development of early airways obstruction in smokers. PMID- 8430952 TI - Activated T-lymphocytes and macrophages in bronchial mucosa of subjects with chronic bronchitis. AB - To examine the nature and the degree of leukocyte infiltration and to determine the state of activation of cells in bronchial mucosa of subjects with chronic bronchitis, bronchoscopy was performed in 10 subjects with a history of cigarette smoking and chronic sputum production and in six normal nonsmoking control subjects. Lobar bronchial biopsies were examined using histochemical and immunohistochemical techniques. Subjects with chronic bronchitis had an increased number of total leukocytes (CD45 positive cells), both in the epithelium and in the lamina propria, than did the control subjects (p < 0.05), whereas the numbers of neutrophils, eosinophils, and mast cells were similar in the two groups. There was a significant increase in the numbers of macrophages (p < 0.01) and of T lymphocytes (CD3 positive cells) (p < 0.05) in the lamina propria of chronic bronchitics, whereas the relative proportions of CD4 and CD8 positive cells were similar in the bronchitics and the control subjects. Subjects with chronic bronchitis also had an increased expression of markers of lymphocyte activation, i.e., an increased number of interleukin-2 receptor positive cells (CD25 positive cells) (p < 0.05) and an increased number of very late activation antigen (VLA-1) positive cells (p < 0.05). In conclusion, the present study provides evidence for mononuclear cell infiltration and for T-cell activation in bronchial mucosa of subjects with chronic bronchitis, supporting the involvement of these cells in the pathogenesis of the disease. PMID- 8430953 TI - T cell-mediated induction of airway hyperresponsiveness and altered lung functions in mice are independent of increased vascular permeability and mononuclear cell infiltration. AB - Previously it was demonstrated that during delayed-type hypersensitivity reactions (DTH) to picryl chloride (PCl) in murine lungs, as a model for cellular IgE-independent immunity, tracheal hyperreactivity and increased pulmonary resistance are induced. In the present study it is demonstrated that after pretreatment with 5HT-2 antagonists, such as ketanserin and methysergide, DTH lung reactions to PCl in mice are suppressed. The increase in vascular permeability, detectable at 2 h after intranasal hapten challenge and probably necessary for the development of a classic DTH reaction, as was demonstrated in skin DTH models, as well as the classic late inflammatory component of lung DTH, is inhibited. However, in vitro tracheal hyperreactivity to the cholinergic receptor agonist carbachol and increased pulmonary resistance in vivo, both induced during the development of these inflammatory DTH lung reactions, are not affected by 5HT-2 receptor antagonist pretreatment. These results indicate that the actual presence of increased vascular permeability and mononuclear infiltrates is not a prerequisite for the development of changed lung functions and tracheal hyperresponsiveness. Thus in mice, serotonin-independent mechanisms that appear during T cell-dependent lung immune reactions induce airway hyperresponsiveness and increased pulmonary resistance. PMID- 8430954 TI - Increased lower airways responsiveness associated with sinusitis in a rabbit model. AB - The association between sinusitis and asthma has been clinically recognized, but its precise nature is controversial. We studied the relationship between sinusitis and lower airways function in a rabbit model of sterile maxillary sinusitis induced by the chemotactic complement fragment C5a des arg. Animals kept in a head-up position following experimental sinusitis demonstrated a significant increase in airways responsiveness (AWR) to histamine. In contrast, animals of which the sinuses were injected with a saline diluent and in which no sinus inflammation developed had no increase in AWR. Experiments were subsequently carried out to investigate some of the potential mechanisms for these observations. A group of rabbits in which a distal site of inflammation was induced did not demonstrate increased AWR. Likewise, when sinus inflammation was established but passage of fluid to the lower airways was prevented, either by intubation or by head-down positioning, there was no change in AWR. A fourth experiment was designed to decrease complement factor activity before placing the animals in a head-up position. This led to the same degree of increased AWR. Neither the histology nor the bronchoalveolar lavage data demonstrated significant lower airways inflammation in any group. We conclude that sterile sinusitis can increase lower airways responsiveness to histamine in a rabbit model. The most likely mechanism for this effect is the postnasal dripping of cells or cell products into the lower airway. The role of a nasobronchial reflex or inflammatory mediator absorption could not be demonstrated in this model. PMID- 8430955 TI - Oxygen radicals contribute to antigen-induced airway hyperresponsiveness in conscious sheep. AB - We previously showed that oxygen radicals can induce airway hyperresponsiveness (AHR) in allergic sheep. The purpose of this study was to determine whether antigen challenge results in the generation of free oxygen radicals and if these radicals contribute to antigen-induced AHR. We first determined baseline airway responsiveness in seven Ascaris suum-sensitive sheep by calculating the cumulative provocative concentration of carbachol in breath units (BU; one BU defined as one breath of a 1% wt/vol carbachol solution) that increased specific lung resistance (SRL) 400% over baseline (PC400). On a different day, the sheep underwent inhalation challenge with A. suum antigen, SRL was measured before and immediately after challenge and then hourly for 2 h, at which time SRL had returned to baseline. The postchallenge PC400 was then measured. This procedure was repeated on separate occasions, each at least 14 days apart, except that the sheep were treated with an aerosol of catalase (CAT; 38 mg in 3 ml deionized water), the enzyme that catalyzes the decomposition of hydrogen peroxide (H2O2), at three different times: Trial 1, before antigen and then every 30 min after antigen challenge for 2 h; Trial II, 1 and 2 h after antigen challenge; and Trial III, only at 2 h after antigen challenge. In the control trial, antigen challenge caused a transient (mean +/- SEM) 303 +/- 48% increase in SRL over baseline (p < 0.05), and 2 h later, PC400 was reduced to 11.0 +/- 1.7 BU from a prechallenge value of 24.8 +/- 1.9 BU (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430956 TI - Hypersensitivity pneumonitis-like reaction among workers exposed to diphenylmethane [correction to piphenylmethane] diisocyanate (MDI). AB - Isocyanates are well documented as a cause of occupational asthma. A hypersensitivity pneumonitis type of reaction has also been reported but only in a few isolated cases. We investigated nine subjects who complained of respiratory and general symptoms related to workplace exposure. All the subjects had worked in a plant where a resin based on diphenylmethane diisocyanate (MDI) is used in the manufacture of woodchip boards. They underwent inhalation challenges using the MDI resin for progressively increasing periods of time on separate days. In eight subjects, exposure to subirritant amounts of MDI induced a pattern of reaction consistent with hypersensitivity pneumonitis, i.e., significant falls in both FEV1 and FVC associated with a rise in body temperature (> 38 degrees C) and an increase in blood neutrophils (> +2,500/mm3). Bronchoalveolar lavage, performed in two subjects 24 h after the end of challenge exposure, revealed an increase in lymphocytes and neutrophils. Specific immunoglobulin G (IgG) and IgE antibodies to MDI human serum albumin (HSA) conjugates were present in all subjects. We conclude that the MDI resin caused an hypersensitivity pneumonitis type of reaction in at least eight (4.7%) of the 167 potentially exposed workers employed in the plant. These findings indicate that in some workplaces, a hypersensitivity pneumonitis type of reaction may be a more frequent consequence of isocyanate exposure than is usually thought. PMID- 8430957 TI - Temporal trends in hospital-based episodes of asthma care in a health maintenance organization. AB - Studies reporting increased asthma hospitalizations and mortality in the United States and abroad have heightened concern about the changing epidemiology of asthma. We studied 20-yr patterns of acute asthma care occurring at two large community hospitals among members of a large health maintenance organization. The presentation focuses on the conceptualization and operationalization of an "episode" of asthma care, defined as a collection of encounters (emergency room visits, urgency care visits, and hospital admissions) that cluster in time, as well as on changes in episode rates over time. We found a statistically significant increase in asthma episodes among boys younger than 5 yr of age that continued unabated from 1967 to 1987 despite a drop in asthma hospitalization rates starting in 1985. We hypothesize that this difference may reflect a change in emergency room management practices and not a true change in the underlying epidemiology of asthma. The concept of an episode of acute asthma care has not been studied in the literature and represents a potentially useful methodologic innovation. Particularly in the context of managed health care systems, studies of such episodes may be less sensitive than studies of hospital admissions to changes in the organization and delivery of acute asthma care, and thus may be better suited for studying changes in the epidemiology of asthma. PMID- 8430958 TI - Inhaled aeroallergen and storage mite reactivity in a Wisconsin farmer nested case-control study. AB - A nested case-control study was undertaken to assess the role of antibody (Ab) to a panel of antigens associated with hypersensitivity pneumonitis in the development of lung disease among Wisconsin dairy farmers. Immunologic reactivity to a panel of inhaled allergens was assessed in the Ab+ cases and compared to the Ab+ control, Ab- control, and Ab- blue-collar control subjects by skin tests, RAST assays, and a modified American Thoracic Society questionnaire. The most prevalent allergens among the cases as determined by either skin test or RAST assays were the house dust mites (HDM) (21.6%), storage mites (11.2%), grain smuts (11.2%), Cladosporium (7.5%), Aspergillus (6.0%), and cattle (5.2%). No other allergens appeared to be different from in nonfarming populations. Of the storage mite reactors, IgE to Lepidoglyphus destructor (7 of 8) was the most frequently found, followed by Tyrophagus putrescentiae (6 of 8), Glycyphagus domesticus (5 of 8), Chortoglyphus arcuatus (5 of 8), and Acarus siro (2 of 8). L. destructor was also isolated from the farm of one of the cases. There was no difference in the total IgE levels among the groups. Reactions to HDM, storage mites, and grain smuts were significantly more frequent among the cases (p < 0.05). We conclude from this study that there is a significant increase in reactivity to certain inhaled allergens among those dairy farmers reporting barn associated respiratory symptoms that is unrelated to past exposure to the causative agents of farmer's lung disease. PMID- 8430959 TI - Respiratory symptoms in young adults should not be overlooked. AB - The purpose of this study was to examine the relation between development of respiratory symptoms and the rate of change in ventilatory lung function in young adults during a study period of 8 yr. The study population consisted of 391 subjects who were 15 to 40 yr of age at initial examination, when they underwent spirometry and an interviewer-administered ATS-DLD-78-A questionnaire on respiratory health, and who were reexamined 8 yr later. The association between the development of symptoms and the rate of change in FEV1 over time (delta FEV1, ml/yr) was studied in a linear regression model that included the potential confounders and other determinants of the outcome. The presence of modification by such factors as smoking, childhood exposure to environmental tobacco smoke, gender, or atopy was assessed by the significance of interaction terms between potential modifiers and incident symptoms. Subjects who developed wheezing and dyspnea and in whom a doctor diagnosed asthma had a significantly greater average annual change in FEV1 compared with those without respiratory symptoms or asthma (-12.3 ml/yr, SE 5.0; -16.2 ml/yr, SE 5.5; and -42.6 ml/yr, SE 11.5, respectively). When focusing on subjects without a diagnosis of asthma, the associations with appearance of wheezing and dyspnea remained significant. The associations were in general stronger in never smokers compared with smokers and were strongest in ex-smokers. The presence of atopy was a significant modifier, so that in subjects with atopy there was a stronger negative association between the onset of cough and asthma and delta FEV1 than in those without.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430960 TI - Predictors of the new onset of wheezing among middle-aged and older men. The Normative Aging Study. AB - Characteristics potentially associated with the development of wheeze symptoms were examined in a prospective cohort study of 624 middle-aged and older men who initially denied any history of wheezing or asthma. Initial evaluation included spirometry, methacholine challenge testing, allergy skin testing with common aeroallergens, serum total IgE concentration, blood leukocyte count, blood eosinophil count, and postural heart rate change (standing minus supine). The presence or absence of wheezing symptoms at follow-up 3 yr later was assessed by questionnaire. Multiple logistic regression was used to examine initial characteristics as predictors of subsequent wheezing. Current smoking was the strongest independent predictor of the new onset of wheezing (adjusted OR, 14.3; 95% confidence interval (CI), 3.9 to 52.3). The risk of developing new wheezing also increased with age (adjusted OR, 1.6; 95% CI, 0.9 to 2.9 comparing individual subjects 10 yr apart) and postural heart rate change at the initial examination (adjusted OR, 1.8; 95% CI, 1.1 to 3.0 comparing individual subjects differing by 10 beats/min). A significant association between greater methacholine airway responsiveness (PD20FEV1 < or = 16.8 mumol versus PD20FEV1 > 16.8 mumol) and the subsequent development of wheezing was observed among nonsmokers (adjusted OR, 5.2; 95% CI, 2.0 to 13.6) but not among current smokers. Other baseline variables were not independently related to the risk of developing wheezing symptoms. These data suggest that current smoking, age, nonspecific airway responsiveness, and altered autonomic function are independently related to the risk of developing wheezing symptoms in middle-aged and older men. PMID- 8430961 TI - Pubertal growth curves of ventilatory function: relationship with childhood respiratory symptoms. AB - This study describes longitudinal growth patterns of ventilatory function in relation to the growth of standing height and weight of boys and girls aged 12.5 to 18 yr with or without a positive history of prepubertal respiratory symptoms. Ventilatory function was characterized by FVC, FEV1, peak expiratory flow (PEF) and maximal expiratory flow at 50% of the FVC (MEF50), derived from maximum expiratory flow volume (MEFV) curves. Data on respiratory symptoms and MEFV curves were obtained in a longitudinal survey of 404 children from a Dutch secondary school. Measurements were made at 6-month intervals between 1978 and 1985. The subjects selected for analysis comprised 151 boys and 118 girls for whom between nine and 14 measurements were available. In asymptomatic boys, the average peak growth rate of standing height occurred at about 14 yr, whereas the growth rates of the ventilatory function indices peaked about 0.8 (FVC) to 1.5 (MEF50) yr later. Weight growth paralleled that of FVC and FEV1. In girls, growth rates of all indices decreased over the whole age range. Adolescents with a positive history of prepubertal respiratory symptoms exhibited lung growth parallel to asymptomatic subjects, but at a lower level. In symptomatic boys, and to a lesser extent in girls, we found consistently lower levels of FVC, FEV1, and MEF50. We conclude that adolescents with a positive history of prepubertal respiratory symptoms, even if they lose their symptoms, remain at a disadvantage with respect to their ventilatory function when they reach adulthood. PMID- 8430962 TI - Functional alterations accompanying a rapid decline in ventilatory function. AB - In a study of two groups of healthy males matched for age, smoking habits, and duration of follow-up, but differing in the rapidity of decline of FEV1 and/or vital capacity (VC), we measured lung volumes before and after bronchodilator inhalation, forced expiratory flows, diffusion capacity for CO (DLCO), and total respiratory impedance. A discriminant analysis showed that the separation between the two groups was achieved best by DLCO, weight, and FEV1/VC among the smokers and by body height and DLCO among the nonsmokers. The fact that DLCO turns out to discriminate between people with a rapid and a normal spirographic decline in the present group points to the possibility of using this measurement, in combination with FEV1/VC and weight, as a predictor of rapid decline of lung function in middle-aged healthy male smokers. PMID- 8430963 TI - Preservation of sustainable inspiratory muscle pressure at increased end expiratory lung volume. AB - Previous studies in isolated muscles have shown that decreases in muscle length reduce the loss of force resulting from fatigue in response to repeated maximal stimulations. However, increases in end-expiratory lung volume (EEV), which presumably decrease the length of the inspiratory muscles, appear to make the inspiratory muscles more susceptible to fatigue. To address this paradox, we studied the influence of changes in EEV on inspiratory muscle fatigue resulting from repeated maximal voluntary inspirations for 15 min in normal humans. Tidal volume and breath timing were constant between runs. Fatigue runs were compared with atmospheric, positive or negative pressures applied to the mouth, sufficient to change EEV by approximately +30% or -20% of inspiratory capacity. Although the maximal initial pressure-time product for the inspiratory muscles (PTmus) was reduced by increased EEV, sustainable PTmus was not significantly affected. In contrast, both initial and sustainable pressure-time products for the diaphragm were reduced at elevated EEV. The rate at which the fatigue process developed was also reduced at increased EEV. There were no significant effects of decreased EEV on any measured pressures. We conclude that when EEV is elevated, within a moderate range, sustainable inspiratory muscle pressure is preserved. However, the contribution of the diaphragm to inspiratory pressure development during fatigue may be uniquely compromised by increased EEV. PMID- 8430964 TI - Bronchoconstriction-induced hyperinflation assessed by thoracic area measurement in guinea pigs. AB - The changes in end-expiratory lung volume (EELV) accompanying histamine-induced bronchoconstriction were compared for two routes of drug administration in anesthetized, paralyzed, and mechanically ventilated guinea pigs. Changes in EELV were estimated from measurements of thoracic cross-sectional area, assessed from the voltage induced by an external uniform magnetic field in a pickup coil encircling the rib cage. Increasing doses of histamine were administered as bolus injections in Group 1 (n = 7) and as nebulizations in Group 2 (n = 7). After each bronchial challenge, the maximum change in EELV and the associated intrinsic positive end-expiratory pressure (PEEPi) were measured at the same time. In both groups, bronchoconstriction was accompanied by an increase in EELV, which was related to the degree of bronchoconstriction and reached about 70 to 100% of the basal functional residual capacity. The increases in EELV were linearly related to the PEEPi values (p < 0.001) and did not depend on the route of histamine administration. These results indicate that dynamic hyperinflation is not the only mechanism involved in lung volume response to bronchoconstriction and suggest that gas trapping may have occurred in alveolar spaces. PMID- 8430965 TI - A double-blind study of troleandomycin and methylprednisolone in asthmatic subjects who require daily corticosteroids. AB - A group of 75 subjects with asthma requiring daily corticosteroids for control were enrolled in a 2-yr, double-blind, placebo-controlled study of the use of troleandomycin combined with methylprednisolone, compared with methylprednisolone alone, for the management of their asthma. The primary outcome variables were determination of the lowest stable methylprednisolone dose and assessment of corticosteroid side effects. Methylprednisolone dose was adjusted to maintain optimal control of asthma symptoms. A total of 30 patients receiving TAO and 27 patients receiving placebo completed 1 yr; 17 on TAO and 8 on placebo completed 2 yr of double-blind participation. Control of asthma was equivalent in both groups. The vast majority of patients in both groups achieved alternate-day dosing (29 of 30 on TAO and 23 of 27 on placebo in the first year). The lowest stable doses of methylprednisolone achieved were 10.4 mg/day (placebo) versus 6.3 mg/day (TAO) in the 1-yr group (p = 0.03). However, the baseline dose was also significantly higher in the placebo group (22.8 versus 17.6 mg/day in the TAO group). Therefore, the reductions in methylprednisolone dose were not significantly different between treatment groups. Differences were observed between the two treatment groups in serum IgG, fasting blood sugar, serum cholesterol, and progression of osteoporosis. In each instance the more unfavorable response occurred in those subjects receiving TAO. We conclude that the addition of TAO to methylprednisolone was not accompanied by a reduction in corticosteroid side effects compared with treatment with methylprednisolone alone. Furthermore, no evidence was found for a subset of "TAO responders."(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430966 TI - The structure of large and small airways in nonfatal and fatal asthma. AB - Asthma is characterized by excessive airway narrowing and airway wall inflammation. In cases of fatal asthma, increased thickness of the airway wall is observed and may account for excessive airway narrowing when smooth muscle contracts. This study was undertaken to examine airway dimensions in large and small airways in both fatal and nonfatal cases of asthma. Airway wall areas (total, inner, and outer relative to smooth muscle layer), epithelial integrity, smooth muscle shortening, and the areas of smooth muscle, cartilage, and mucous glands were compared in transverse sections of large and small airways of subjects dying of asthma (fatal asthma, n = 11), those dying suddenly of nonrespiratory diseases and having a definite history of asthma (nonfatal asthma, n = 13), and those dying suddenly without any history of respiratory illness (control, n = 11). Airways were grouped by size using the basement membrane perimeter for comparison. All areas were expressed as areas per millimeter of basement membrane. In cartilaginous airways, the cases of fatal asthma had greater (p < 0.05) total wall, inner wall, outer wall, smooth muscle, mucous gland and cartilage areas than did control and nonfatal cases. The inner wall area was greater in the fatal and nonfatal cases than in the control cases (p < 0.05) in the small cartilaginous airways and membranous bronchioles (MB). In small MB (perimeter < 2 mm), the total and outer wall areas were greater (p < 0.05) in cases of fatal and nonfatal asthma than in control cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8430967 TI - Pertussis is rare in human immunodeficiency virus disease. AB - Many adults are susceptible to pertussis, and Bordetella pertussis has been isolated from five patients with HIV disease. The prevalence of B. pertussis in 60 HIV-infected adults with nasopharyngeal (NP) swab cultures were studied and questionnaires were used that assessed HIV-related risk behaviors and disease status, immunization history, and symptoms of respiratory disease. Although 72% had cough and 33% had cough for > 14 days, no nasopharyngeal (NP) swab cultures were positive for Bordetella species. Of the 44 (73%) patients who had follow-up NP swab cultures at 6 months, all were still negative. On the basis of these data from our HIV-infected population, the estimated population prevalence of pertussis is zero, with an upper 95% confidence limit of 0.00065, or fewer than 6.5 cases of pertussis per 10,000 HIV-infected adults. Given this low prevalence, HIV-infected patients with respiratory symptoms do not appear to be a reservoir for B. pertussis in the community. PMID- 8430968 TI - Diagnosis of primary tuberculosis in children by amplification and detection of mycobacterial DNA. AB - Standard microbiologic techniques were compared with a rapid diagnostic method based on the amplification by polymerase chain reaction (PCR) of a fragment of the IS6110 insertion element (present in multiple copies in the Mycobacterium tuberculosis genome) for the detection of M. tuberculosis in specimens obtained from children diagnosed as having primary tuberculosis on clinical grounds. Two (n = 7) or three (n = 15) gastric aspirates were obtained from the 22 children with primary tuberculosis. All specimens were negative for mycobacteria by acid fast staining and culture. When DNA was purified from the clinical specimens and aliquots of each sample were amplified in duplicate, 15 of 59 (25%) specimens gave at least one positive result. Increasing beyond two the number of times that samples were tested did not appreciably improve sensitivity. Testing multiple samples from the same individual increased the diagnostic yield. Thus, when three different samples from the same subject were tested two times each, two or more positive results were obtained from 9 of 15 children with primary tuberculosis but 0 of 17 control subjects. Samples from children with symptoms, recent contact with patients with active tuberculosis, vesicular tuberculin responses, or abnormal chest radiographs were more frequently positive than those from patients whose only manifestation of tuberculosis was a positive (but not vesicular) tuberculin response. Thus, M. tuberculosis DNA can be detected by PCR in gastric aspirates of many children with primary tuberculosis, despite that specimens from these patients are negative by culture. Multiple samples must be tested to optimize the diagnostic yield. PMID- 8430969 TI - Respiratory control during exercise in patients with cardiovascular disease. AB - The pathophysiologic mechanism for exertional dyspnea, the main symptom of patients with heart failure, has not been fully clarified. To determine the relationship between exercise hyperpnea and the lactic acidosis in patients with heart failure, we evaluated ventilation during incremental exercise both below and above the lactic acidosis threshold in 16 normal subjects and in 48 patients with cardiovascular disease while expired gas was analyzed continuously. The peak oxygen uptake and oxygen uptake at the lactic acidosis threshold decreased significantly as the New York Heart Association (NYHA) functional class severity increased. the slope of the increase in ventilation to the increase in oxygen uptake (delta VE/delta VO2) at work rates below the lactic acidosis threshold did not differ between normal subjects and patients with heart failure. Above the lactic acidosis threshold, however, the slope of delta VE/delta VO2, which was higher than that below the lactic acidosis threshold in each of four groups, was steeper in patients in NYHA Class II (60.8 +/- 17.9) and Class III (66.5 +/- 21.2) when compared with that in the normal subjects (46.6 +/- 13.5) or the patients in NYHA Class I (46.1 +/- 10.3). The lactic acidosis caused by decreased oxygen transport to working muscles accounts for the higher ventilation during exercise in cardiac patients. These data suggest that the increased ventilation during exercise, which must be related to exertional dyspnea, in patients with cardiovascular disease is primarily the consequence of a stimulus to regulate arterial pH. PMID- 8430970 TI - Ultrasound study in unilateral hemithorax opacification. Image comparison with computed tomography. AB - The diagnostic capability of chest ultrasonography was assessed for use in evaluation of patients presenting with opacification of unilateral hemithorax on chest radiography. Hemithorax opacification provided an "ultrasonic window" for ultrasonic wave penetration to detect any underlying diseases. Fifty patients were included over a study period of 24 months. All had received both chest ultrasonography (US) and computed tomography (CT) examinations, and their underlying diseases had been confirmed by various methods. Comparisons between the findings of chest US and of CT were made in three compartments: pleura, parenchyma, and mediastinum. Diagnostic sensitivity and specificity of chest US was defined by using CT as the "gold standard." The ability of US to detect underlying diseases was comparable to that of CT in pleural and parenchymal lesions. But US was inferior to CT for demonstration of mediastinal lesions. The diagnostic sensitivity of US was 95.1% in pleural lesions, 82.8% in parenchymal lesions, and only 30% in mediastinal lesions. US missed 14 lesions demonstrated by CT (seven mediastinal lesions, five parenchymal tumors, and two pleural nodules), but it showed six lesions that CT had failed to detect (four focal pleural thickening and two parenchymal tumors). US-related procedures were performed (thoracentesis in 33 patients, pleural biopsy in 10 patients, and US guided aspiration/cutting biopsy in 11 patients) with a high diagnostic yield and no complications. The conclusion was that chest ultrasonography is useful, particularly as a first-step examination for patients with total or nearly total opacification of the hemithorax. PMID- 8430971 TI - Nasal continuous positive airway pressure in the treatment of tracheobronchomalacia. AB - The effect of nasal continuous positive airway pressure (CPAP) was assessed in three patients with tracheobronchomalacia (TBM) who failed conventional medical management. Using physiologic measures of airflow and fiberoptic bronchoscopy, we evaluated expiratory airflow and airway collapse during the acute administration of nasal CPAP. FVC increased and dynamic airway collapse [slow vital capacity minus forced vital capacity (SVC--FVC)] decreased with increasing levels of CPAP. Notching associated with airway collapse was observed in the baseline spirograms of all three patients, and it disappeared with the addition of nasal CPAP. Fiberoptic bronchoscopy confirmed the severity of TBM in each patient and documented an acute improvement in expiratory airway collapse with the addition of nasal CPAP. Intermittent nasal CPAP was then added to the patients' treatment regimens, improving the course of their disease. Specific treatment outcomes varied from patient to patient, but they included improved sputum production, atelectasis, exercise tolerance, and patient symptoms plus reduced need for medical care. These findings suggest that the addition of intermittent nasal CPAP to routine medical therapy may be of benefit to patients with severe TBM unresponsive to conventional medical management. PMID- 8430972 TI - An amphipathic alpha-helical decapeptide in phosphatidylcholine is an effective synthetic lung surfactant. AB - An idealized model amphipathic alpha-helical decapeptide was synthesized and tested for efficacy as a totally synthetic lung surfactant in simple mixtures with dipalmitoylphosphatidylcholine (DPPC). Quasi-static lung compliance was restored to 92 +/- 3% of the unlavaged value at a pressure of 5 cm H2O in an in vitro lavaged rat lung model. A sustained improvement in gas exchange was also observed when guinea pigs were treated with the synthetic lung surfactant in an in vivo lavaged lung model. DPPC/peptide mixtures rapidly formed low surface tension films in the pulsating bubble surfactometer consistent with a mechanism in which the lipid and peptide mixture spreads rapidly in the lavaged lung to minimize the surface tension at the air/tissue interface. This decapeptide sequence is active in mixtures with DPPC whether the residues are in the all L or all D conformation. However, a peptide with identical sequence, but with alternating D and L amino acid residues, is relatively inactive. Positive charge interactions are not important since a peptide with formylated lysine residues is active. The activity of these decapeptides, with sequences unrelated to any of those in natural lung surfactants, shows that the classic amphipathic alpha helical hypothesis may be useful in designing peptides that will be effective synthetic lung surfactants in binary mixtures with DPPC. The data demonstrate that a small water-soluble synthetic peptide containing an amphipathic alpha helical structure combined solely with the major lipid of natural lung surfactant is effective in restoring lung compliance and gas exchange in surfactant deficient lungs and may be useful in treatment of the respiratory distress syndromes. PMID- 8430973 TI - Airway and pulmonary tissue responses to capsaicin in guinea pigs assessed with the alveolar capsule technique. AB - We studied the effects of capsaicin on airway and lung tissue mechanics in anesthetized and tracheostomized guinea pigs that were mechanically ventilated at constant tidal volume (8 ml/kg) and breathing frequency (60 breaths/min). Dose response curves to intravenously infused capsaicin (1, 10, and 100 micrograms/kg) were performed (five animals for each dose, one dose per animal). We measured airflow, volume (by integration of the flow signal), tracheal pressure, and alveolar pressure with an alveolar capsule. Capsaicin induced a dose-dependent increase in airway resistance, tissue resistance, and dynamic elastance. The relationship between airway pressure and flow was fitted by a quadratic (Rohrer) equation. Airflow became more turbulent after infusion of capsaicin. After infusion of 100 micrograms/kg capsaicin, airway pressure (at flow rates of 10 ml.s-1) increased from 3.03 +/- 0.40 (mean +/- SEM) to 9.58 +/- 1.88 cm H2O, whereas the pressure corresponding to viscoelastic properties of lung tissue increased from 0.92 +/- 0.14 to 8.58 +/- 1.12 cm H2O. We conclude that infusion of capsaicin results in mechanical effects in both airways and pulmonary tissue. PMID- 8430974 TI - Psychologic side effects of therapy with corticosteroids. PMID- 8430975 TI - Respiratory mechanics in infants: physiologic evaluation in health and disease. American Thoracic Society/European Respiratory Society. PMID- 8430976 TI - Tuberculosis in the United States. PMID- 8430977 TI - Diurnal and nocturnal diuresis in OSA. PMID- 8430978 TI - Syndrome of Rochalimaea henselae adenitis suggesting cat scratch disease. AB - OBJECTIVE: To describe a clinical syndrome of cat scratch disease caused by Rochalimaea henselae, including methods for isolation of the organism from tissue and for identification. DESIGN: Case series. SETTING: U.S. Air Force referral hospital infectious diseases clinic. PATIENTS: Two previously healthy patients. MAIN MEASUREMENTS AND RESULTS: Two immunocompetent patients who had handled cats developed unilateral upper-extremity adenitis associated with a distal papular lesion and fever. The adenitis and distal lesions persisted and progressively worsened. Cultures of the involved lymph nodes from both patients grew R. henselae, a recently described organism associated with bacillary angiomatosis and peliosis hepatis in human immunodeficiency virus-infected patients and with bacteremia in immunocompromised and immunocompetent hosts. The organism was characterized as oxidase negative and X-factor dependent and had a characteristic pattern in analysis of whole-cell fatty acids differing from Afipia felis, a bacterium that has been associated with cat scratch disease. The identity of the isolate was confirmed by analysis of whole-cell fatty acids using gas chromatography and by amplification of the citrate synthetase gene sequence and analysis of the polymerase chain reaction-amplified product. The organisms were broadly susceptible to a variety of antimicrobials by broth microdilution; however in-vitro resistance to first-generation cephalosporins correlated with clinical failure of therapy. CONCLUSION: Rochalimaea henselae can be a cause of cat scratch disease in immunocompetent patients. PMID- 8430979 TI - Estrogen protection against bone resorbing effects of parathyroid hormone infusion. Assessment by use of biochemical markers. AB - OBJECTIVE: Because parathyroid hormone (PTH) stimulates bone resorption, resistance to its actions might help maintain bone mass. We tested the hypothesis that the effects of estrogen on bone are accomplished in part by decreasing the sensitivity of the skeleton to the resorbing effects of PTH. STUDY DESIGN: Comparison of response to PTH infusion in untreated and estrogen-treated postmenopausal women with osteoporosis. INTERVENTION: (1-34) human PTH, 0.55 U/(kg.h), was infused intravenously over 20 hours. SETTING: The inpatient clinical research unit of a referral hospital. PATIENTS: Women with primary postmenopausal osteoporosis who were untreated (n = 15) or treated with estrogen (n = 17). MAIN OUTCOME MEASURES: Skeletal turnover indices including hydroxyproline, deoxypyridinoline, pyridinoline, tartrate-resistant acid phosphatase, alkaline phosphatase, bone Gla protein, and insulin-like growth factor-1. RESULTS: All basal indices were higher in untreated than in estrogen treated women, but statistical differences were seen only for deoxypyridinoline and pyridinoline. During the 20-hour infusion, hydroxyproline/creatinine increased 0.023 mumol/mumol in untreated women but only 0.010 mumol/mumol in estrogen-treated women (P < 0.05). Corresponding changes for deoxypyridinoline/creatinine were 14.6 mumol/mumol and 3.5 mumol/mumol (P = 0.06). Tartrate-resistant acid phosphatase and pyridinoline increased only in untreated group. A circadian rhythm in circulating bone Gla protein was seen in both groups without clear PTH-induced effects or differences between groups. Alkaline phosphatase levels decreased and insulin-like growth factor-1 levels increased in both groups with no distinction between untreated and estrogen treated women [corrected]. CONCLUSION: The estrogenized postmenopausal osteoporotic skeleton is less sensitive to the bone resorbing effects of acutely administered PTH. There are no differential effects on bone formation. PMID- 8430980 TI - Restenosis after arterial injury caused by coronary stenting in patients with diabetes mellitus. AB - OBJECTIVE: To determine whether diabetic patients, when compared with nondiabetic patients, have a higher incidence of restenosis after coronary stenting, and, if so, whether restenosis is attributable to lesion or procedural differences or to a greater biologic tendency for late loss of minimum diameter in diabetic patients. DESIGN: Case series. SETTING: Tertiary care referral center. PATIENTS: Two hundred twenty consecutive patients with coronary artery disease who were referred for placement of a Palmaz-Schatz stent in either a native coronary artery or a saphenous vein graft. RESULTS: Based on a traditional dichotomous definition of restenosis (> or = 50% stenosis at follow-up), lesions in diabetic patients had a significantly greater restenosis rate (55%) than lesions in nondiabetic patients (20%; P = 0.001). Vessel size, lesion length, pre-procedure lesion severity, procedural outcome, and acute gain (the difference between minimum lumen diameter before and after the procedure) were similar in the diabetic and nondiabetic groups. However, at follow-up, stents in diabetic patients had a smaller lumen diameter (1.66 +/- 1.18 mm) compared with those in nondiabetic patients (2.24 +/- 0.93 mm; P = 0.004), as well as a greater percent stenosis (49% compared with 32%; P = 0.002). Thus, the increased restenosis rate in stents in diabetic patients (55% compared with 20%; P = 0.001) is secondary to increased late loss of minimum lumen diameter (1.66 +/- 1.28 mm compared with 1.23 +/- 0.97 mm; P = 0.04). CONCLUSIONS: After arterial injury produced by stent placement, diabetic patients have a significantly greater incidence of restenosis because of greater late loss at the treatment site. Because elastic recoil or vasospasm contributes little to stent restenosis, the increased late loss of minimum lumen diameter in diabetic patients suggests that they have a greater predisposition to intimal hyperplasia. PMID- 8430981 TI - Is body fat topography a risk factor for breast cancer? AB - OBJECTIVE: To determine whether body fat distribution is associated with the onset of breast cancer. DESIGN: Case-control study. SETTING: Memorial Sloan Kettering Cancer Center, New York, New York. PATIENTS: Three hundred thirteen healthy, white women, born in the United States. MEASUREMENTS: Waist and hip circumferences were measured on the day before diagnostic breast surgery, and an extensive risk assessment of clinical and family history data was done. After the results of diagnostic breast surgery were obtained, study participants were divided into three groups: women with breast cancer (n = 156); controls (n = 126) with benign tissue at biopsy and an average risk for breast cancer; and high-risk women (n = 31), defined as being at a risk for breast cancer development of 1% per year, based on rigorous histologic or clinical criteria. RESULTS: The waist to-hip ratios (WHR) were identical (mean +/- SD) in case patients (0.80 +/- 0.06), controls (0.80 +/- 0.06), and high-risk women (0.80 +/- 0.08). Further, no trend could be detected between increasing WHR and breast cancer risk; the estimated relative risk for cancer incidence in women with WHR greater than or equal to 0.81 was 0.78 (95% Cl, 0.36 to 1.71), compared with women with WHR of less than 0.73. No difference in WHR was noted between the case patients and controls when analyzed separately according to menopausal status, age, absolute weight, or relative weight. CONCLUSION: In the women studied, body fat topography as defined by WHR was not associated with breast cancer development. PMID- 8430982 TI - Bacillary angiomatosis and bacillary splenitis in immunocompetent adults. PMID- 8430983 TI - Magnetic healing, quackery, and the debate about the health effects of electromagnetic fields. AB - Although the biological effects of low-frequency electromagnetic radiation have been studied since the time of Paracelsus, there is still no consensus on whether these effects are physiologically significant. The recent discovery of deposits of magnetite within the human brain as well as recent, highly publicized tort litigation charging adverse effects after exposure to magnetic fields has rekindled the debate. New data suggest that electromagnetic radiation generated from power lines may lead to physiologic effects with potentially dangerous results. Whether these effects are important enough to produce major epidemiologic consequences remains to be established. The assumption of quackery that has attended this subject since the time of Mesmer's original "animal magnetism" investigations continues to hamper efforts to compile a reliable data base on the health effects of electromagnetic fields. PMID- 8430984 TI - What is internal medicine? PMID- 8430985 TI - Rochalimaea's role in cat scratch disease and bacillary angiomatosis. PMID- 8430986 TI - Pneumococcal disease and HIV infection. PMID- 8430987 TI - Pneumococcal disease and HIV infection. PMID- 8430988 TI - Cotrimoxazole prophylaxis for toxoplasmosis. PMID- 8430989 TI - Mitral regurgitation and MI mortality. PMID- 8430990 TI - Central nervous system infection with Mycobacterium kansasii. PMID- 8430991 TI - Pretraining for international medical graduates. PMID- 8430992 TI - Pretraining for international medical graduates. PMID- 8430993 TI - Pretraining for international medical graduates. PMID- 8430994 TI - Pretraining for international medical graduates. PMID- 8430995 TI - Full-time clinicians as teachers. PMID- 8430997 TI - Blood rheology and 2,3-diphosphoglycerate levels after erythropoietin treatment. AB - Twenty-seven transfusion dependent patients with end-stage renal disease on long term dialysis had blood cell counts, serum chemistries, blood pressure, and whole blood viscosity measured, as well as having transfusion requirements assessed. Three months after the institution of recombinant human erythropoietin (rHU-EPO) (75 u per kg per wk), there was an 88 percent fall in transfusion requirement. After four months, the hematocrit increased from 24 +/- 3.8 to 25.6 +/- 4.2 percent, mean corpuscular volume from 93 +/- 4.9 to 97 +/- 6.6 fl, 2-3 diphosphoglycerate (2,3-DPG) from 13.2 +/- 3.2 to 15.6 +/- 4.3 microM per g of Hb. Whole blood viscosity fell from 14.1 +/- 2.1 to 12.7 +/- 2.3 seconds, and ferritin levels fell from 3282 +/- 3889 to 2131 +/- 2441 ng per ml. In eight patients in whom the dose of rHU-EPO was further increased by up to 50 units per kg three times weekly for three months, the hematocrit rose further to 29.3 +/- 3.0 percent and the rise in hematocrit was accompanied by a further increase in 2,3-DPG to 17.9 +/- 2.8 microM per g of Hb (p < 0.03). There were no major side effects or vascular complications. PMID- 8430996 TI - Long-term oral aluminum administration in rabbits. II. Brain and other organs. AB - Aluminum (Al) was given orally as a citrate salt in either hard or soft water in combination with low or normal dietary calcium intake over the duration of 12 months using 60 healthy, young adult male New Zealand white rabbits, age four to seven months, divided into six groups. Although decreased weight gain was noted, no significant histological changes were found in the central or peripheral nervous system or in multiple other organs except for liver, nor were tissue levels of Al elevated in brain or liver. However, Al in renal tissue was increased after 52 weeks of treatment in Group 1 (which received Al and a low calcium diet), in spleen in Groups 1 and 2 (on Al and a low calcium diet), and in bone in Group 1. Thus, although the mature intestine acts as a relatively impermeable barrier, some Al is, in fact, absorbed and deposited. PMID- 8430998 TI - Alpha-1 antitrypsin protease inhibitor typing in immobilized pH gradients. AB - Alpha-1 antitrypsin deficiency is a cause of liver disease in neonates and emphysema in adults. Protein phenotypes are identified by isoelectric focusing using polyacrylamide gels. The Pharmacia Phastsystem was utilized for electrophoresis in miniature gels to identify heterozygotes for the deficiency. Protein phenotypes were identified by isoelectric focusing in a fixed pH gradient from 4.3 to 5 using the Pharmacia Phastsystem for automated electrophoresis and staining of gels. The gradient is formed with Immobilines to create gels of dimensions 50 x 43 x 0.5 mm. The processing time for 16 specimens is one hour and 45 minutes. This method is a rapid, automated method for the analysis of alpha-1 antitrypsin phenotypes and for establishing the diagnosis of a genetic deficiency of this protein. PMID- 8430999 TI - Alterations in von Willebrand factor antigen in premature infants with respiratory distress syndrome and chronic lung disease. AB - Elevated levels of von Willebrand Factor Antigen (vWF:Ag) may occur in the presence of endothelial injury, a component in the pathology of acute pulmonary insufficiency. The vWF:Ag levels were examined in 13 well infants (controls) and 20 infants with respiratory distress syndrome (RDS), nine of whom developed bronchopulmonary dysplasia (BPD). All infants were very low birth weight (730 to 1500 g) and premature (25 to 34 weeks estimated gestational age). Plasma samples were obtained at birth and weekly through 28 days of age and frozen at -70 degrees C. The vWF:Ag was quantified by the enzyme linked immunosorbent assay (ELISA) method for 138 plasma specimens; in addition, 77 samples were analyzed for multimer pattern by SDS-agarose (1.7 percent) electrophoresis and densitometric scanning. All groups had elevated mean levels of vWF:Ag, compared to adults. Although levels remained stable over the four week period, the group of infants with BPD had a significantly high mean level of vWF:Ag at 21 days than those groups without BPD (p < 0.05). Visual examination of vWF multimer patterns revealed absence of unusually large vWF multimers and triplet patterns suggestive of increased proteolytic degradation of von Willebrand factor. However, densitometer scanning revealed that samples with higher vWF:Ag levels (> 200 percent) had increased amounts of moderate to smaller sized multimers, regardless of presence or absence of BPD. It is our conclusion that von Willebrand factor antigen levels are nonspecifically elevated in premature infants and that chronic lung disease is associated with even higher plasma values, possibly owing to pulmonary endothelial injury. PMID- 8431000 TI - Platelet abnormalities in diabetes mellitus. AB - Patients with diabetes mellitus have an increased risk of thrombosis and accelerated atherogenesis. Increased platelet adhesion and aggregation are noted in vitro. This paper reviews known platelet abnormalities found in patients with diabetes mellitus (DM) and examines the pathophysiology associated with these abnormalities. Four general platelet regions or functional units can be involved in aberrant chemistry, structure and/or function. These include (1) the membrane, (2) granules, (3) intermediary metabolism, and (4) other factors and/or platelet responses to various substances. In regard to the abnormalities of the membrane, there is an increased binding of fibrinogen in diabetic rats and increased membrane rigidity. There are increases in glycoprotein Ib and glycoprotein IIb/IIIa. Related to granule function, increased levels of plasma serotonin, histamine and beta thromboglobulin are found. Alterations of intermediary metabolism involving the prostaglandin pathways, arachidonic acid, Vitamin E, and lipids have been reported. Other factors which are not well characterized include abnormalities of stem cell response to growth factors and thrombopoiesis, as noted indirectly through alterations of platelet volumes. It is proposed that these platelet abnormalities result in increased thrombosis and/or an acceleration of the atherosclerotic process in at least some patients with diabetes mellitus. PMID- 8431001 TI - The effect of vitamins C and E on lipid peroxidation in stored erythrocytes. AB - Vitamins C and E are both naturally occurring free radical scavengers; as such, their presence assists various other mechanisms in decreasing numerous disruptive free radical processes from taking place, including lipid peroxidation (LP). Vitamin C, being water soluble, is an excellent antioxidant in plasma, while lipid soluble vitamin E is effective in cell membranes. In this communication, our study is reported of the effects of oral vitamin C and E supplementation in human volunteers on stored red cell LP. It was found that supplementation with these vitamins for 10 days prior to blood donation significantly decreased LP in stored red cells in both irradiated and non-irradiated samples in comparison to pre-vitamin red cell LP. Plasma potassium levels were also decreased on days 7 and 14 after storage at 4 degrees C, but not after four additional days (day 18) at 37 degrees C. In agreement with prior studies, in which various metal chelators and other antioxidants were shown to decrease LP, this study further supports the suggestion that, in addition to adding various important nutrient solutions to donor blood, as well as the possible in vitro addition of various metal chelators and other antioxidants, the oral supplementation with vitamin free radical scavengers may further improve the longevity and viability of stored red cells. PMID- 8431002 TI - The International Normalized Ratio: a dispassionate view. PMID- 8431004 TI - Therapeutic effect of cefozopran (SCE-2787), a new parenteral cephalosporin, against experimental infections in mice. AB - The therapeutic effect of cefozopran (SCE-2787), a new semisynthetic parenteral cephalosporin, against experimental infections in mice was examined. Cefozopran was more effective than cefpiramide and was as effective as ceftazidime and cefpirome against acute respiratory tract infections caused by Klebsiella pneumoniae DT-S. In the model of chronic respiratory tract infection caused by K. pneumoniae 27, cefozopran was as effective as ceftazidime. The therapeutic effect of cefozopran against urinary tract infections caused by Pseudomonas aeruginosa P9 was superior to that of cefpirome and was equal to those of ceftazidime and cefclidin. In addition, cefozopran was more effective than ceftazidime and was as effective as flomoxef in a thigh muscle infection caused by methicillin-sensitive Staphylococcus aureus 308A-1. Against thigh muscle infections caused by methicillin-resistant S. aureus N133, cefozopran was the most effective agent. The potent therapeutic effect of cefozopran in those experimental infections in mice suggests that it would be effective against respiratory tract, urinary tract, and soft tissue infections caused by a variety of gram-positive and gram negative bacteria in humans. PMID- 8431003 TI - Use of rifampin in nonstaphylococcal, nonmycobacterial disease. AB - Rifampin has very broad antimicrobial properties with in vitro activities against many bacteria, mycobacteria, higher bacteria, chlamydia, fungi, parasites, and viruses (Table 1). The clinical use of rifampin is more limited, in part because of the lack of in vivo human clinical studies demonstrating its efficacy. Investigators have valid concerns regarding the emergence of resistance of mycobacteria if widespread use of rifampin becomes common, although this has not been well documented. Because rifampin obtains therapeutic levels intracellularly and is distributed widely throughout the body, the antibiotic potentially could be used on a broader scale, but more studies will be needed to demonstrate its clinical utility. PMID- 8431005 TI - In vitro activities of nucleoside analog antiviral agents against salmonellae. AB - Zidovudine (ZDV) has antibacterial activity against many members of the family Enterobacteriaceae, including Salmonella species, and may be responsible for a decrease in the frequency of salmonellosis in persons infected with human immunodeficiency virus (HIV). Other nucleoside analogs, such as didanosine (2',3' dideoxyinosine [ddI]) and zalcitabine (2',3'-dideoxycytidine [ddC]), which have undefined anti-salmonella activity, increasingly are being used in the treatment of HIV infection. To evaluate the anti-Salmonella activity of the antiviral agents ZDV, ddI, ddC, and acyclovir (ACV), we determined MICs for 39 nontyphoidal Salmonella blood isolates. ZDV (MIC for 50% of strains tested [MIC50], 0.5 microgram/ml; MIC range, 0.125 to 4 micrograms/ml) and ddI (MIC50, 8 micrograms/ml; MIC range, 2 to 125 micrograms/ml) had concentration-dependent activity. Anti-Salmonella activity was not observed for ddC or ACV. Nine Escherichia coli blood isolates were inhibited by ZDV (MIC50, 0.125 microgram/ml; MIC range, 0.031 to 1 microgram/ml) to a greater degree than they were by ddI (MIC50, 62.5 micrograms/ml; MIC range, 31 to > 62.5 micrograms/ml). Inoculum size affected susceptibility to ZDV and ddI for Salmonella and E. coli isolates. Resistance to ZDV or to ddI could be induced in vitro in Salmonella isolates, but cross-resistance was not observed. These results indicate that at concentrations achieved during the treatment of HIV infection, ZDV has activity against nontyphoidal salmonellae, although resistance can develop. ddI, ddC, and ACV at currently used dosages would not be expected to be effective in the prevention or treatment of Salmonella infections. PMID- 8431006 TI - MICs and MBCs of clarithromycin against Mycobacterium avium within human macrophages. AB - The inhibitory and bactericidal activities of clarithromycin were determined quantitatively against the intracellular populations of five Mycobacterium avium strains growing in monocyte-derived human macrophages. The MICs were 1.0 microgram/ml, and the MBCs ranged from 16.0 to 64.0 micrograms/ml; these values were similar to the MICs and MBCs found in broth cultures at pH 7.4 and were substantially lower than those found in broth cultures at pHs 6.8 and 5.0. Since the intracellular environment has a neutral or even an acidic pH, relatively low MICs and MBCs found in macrophage cultures can be associated with the fact that the drug concentrations in macrophages are substantially higher than those in the medium in which these cells are cultivated. Pretreatment of the macrophages 2 days prior to infection decreased the MICs twofold in comparison with results of experiments in which the drug was added to already infected macrophages. PMID- 8431007 TI - Preclinical evaluation of antiviral activity and toxicity of Abbott A77003, an inhibitor of the human immunodeficiency virus type 1 protease. AB - A synthetic, symmetry-based inhibitor of the human immunodeficiency virus type 1 (HIV-1) protease, A77003, was evaluated for antiviral activity and cytotoxicity in vitro in human peripheral blood lymphocytes or cell lines H9, CEM, and U937. Toxicity and antiviral activity of the HIV-1 protease inhibitor were compared with those of the reverse transcriptase inhibitors zidovudine and 2',3'-dideoxy 2',3'-didehydrothymidine and human recombinant alpha and beta interferons. Production of infectious virus particles, cell-free p24 antigen, and cell associated viral proteins was reduced 50% by the HIV-1 protease inhibitor at concentrations of 0.12 to 0.26 microM (50% effective concentration [EC50]) in acute infection and 0.2 to 1.7 microM (EC50) in persistent infection. Fluorescence-activated cell sorter analysis of U937 cells persistently infected with HIVIIIB using a monoclonal antibody to HIV also showed a reduction of cell associated viral protein in A77003-treated cells. Furthermore, toxicity of A77003 assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay was not observed at greater than 100 times the EC50. A77003 was more effective in persistent HIV-1 infection than alpha and beta interferons (1,000 U/ml), while zidovudine and 2',3'-dideoxy-2',3'-didehydrothymidine were not active. PMID- 8431008 TI - Hyperoxia and prolongation of aminoglycoside-induced postantibiotic effect in Pseudomonas aeruginosa: role of reactive oxygen species. AB - Hyperoxia prolongs the postantibiotic effect (PAE) of the aminoglycoside tobramycin in Pseudomonas aeruginosa. We tested the hypothesis that the PAE is prolonged because hyperoxia increases free radical flux while tobramycin inhibits the induction of antioxidant defenses. Exposure of P. aeruginosa to hyperoxia (100% O2) for 1 h increased superoxide dismutase, catalase, and glutathione levels. In the presence of tobramycin (1x the MIC), the induction of antioxidant defenses by hyperoxia was nearly abrogated. Neither preexposure of P. aeruginosa to hyperoxia nor supplementation with the antioxidants copper(II) (diisopropylsalicylate)2 (superoxide dismutase-like), catalase, or dimethyl sulfoxide abolished prolongation of the PAE of tobramycin induced by hyperoxia. PMID- 8431009 TI - In vitro activities of meropenem, PD 127391, PD 131628, ceftazidime, chloramphenicol, co-trimoxazole, and ciprofloxacin against Pseudomonas cepacia. AB - In a study of 110 Pseudomonas cepacia isolates from patients without cystic fibrosis, the in vitro potencies of three new compounds, meropenem, PD 127391, and PD 131628, were comparable to those of ceftazidime and ciprofloxacin and exceeded those of chloramphenicol and co-trimoxazole. The MICs of ceftazidime, ciprofloxacin, meropenem, and the PD compounds for 90% of strains tested were < or = 4 micrograms/ml, whereas they were 32 micrograms/ml for chloramphenicol and co-trimoxazole. Data for 20 isolates from patients with cystic fibrosis indicated that the isolates were less susceptible to all seven antibiotics tested, with the most active compounds being meropenem and PD 127391. PMID- 8431010 TI - Fluoroquinolone resistance protein NorA of Staphylococcus aureus is a multidrug efflux transporter. AB - The gene of the Staphylococcus aureus fluoroquinolone efflux transporter protein NorA confers resistance to a number of structurally dissimilar drugs, not just to fluoroquinolones, when it is expressed in Bacillus subtilis. NorA provides B. subtilis with resistance to the same drugs and to a similar extent as the B. subtilis multidrug transporter protein Bmr does. NorA and Bmr share 44% sequence similarity. Both the NorA- and Bmr-conferred resistances can be completely reversed by reserpine. PMID- 8431011 TI - In vitro antimicrobial production of beta-lactamases, aminoglycoside-modifying enzymes, and chloramphenicol acetyltransferase by and susceptibility of clinical isolates of Acinetobacter baumannii. AB - Antimicrobial susceptibility testing was performed on 54 epidemiologically unrelated clinical isolates of Acinetobacter baumannii by using a standard agar dilution technique. On the basis of the in vitro activities, imipenem and doxycycline were the most active agents, whereas amikacin, isepamicin, and the new fluorquinolones ciprofloxacin and ofloxacin presented moderate activity. Cephalosporinase activity was found in 98% of the strains, whereas lactamases of TEM type 1 and one with a pI of 7 to 7.5 were present in 16 and 11% of the strains, respectively. Resistance to aminoglycosides was explained by the production of the three classes of aminoglycoside-modifying enzymes, with predominance of aminoglycoside-3'-phosphotransferase VI in 28% of the strains. PMID- 8431013 TI - Evaluation of synergy between carbovir and 3'-azido-2',3'-deoxythymidine for inhibition of human immunodeficiency virus type 1. AB - 3'-Azido-2',3'-deoxythymidine and carbovir [racemic and (-) enantiomer] were evaluated individually and in combination for antiviral activity against human immunodeficiency virus type 1 replication and cytotoxicity in vitro. The combination of these drugs synergistically inhibited human immunodeficiency virus type 1 replication in C3 and Jurkat cells and in human peripheral blood mononuclear cells, although the same combination also produced synergistic cytotoxicity in human peripheral blood mononuclear cells. PMID- 8431012 TI - Susceptibilities of beta-lactamase-producing and -nonproducing ampicillin resistant strains of Haemophilus influenzae to ceftibuten, cefaclor, cefuroxime, cefixime, cefotaxime, and amoxicillin-clavulanic acid. AB - In in vitro studies we evaluated the susceptibilities of beta-lactamase-producing and -nonproducing, ampicillin-resistant strains of Haemophilus influenzae and compared them with those of ampicillin-susceptible strains. Ampicillin, amoxicillin-clavulanic acid, ceftibuten, cefaclor, cefuroxime, cefixime, and cefotaxime were evaluated by broth microdilution tests and disk diffusion tests. The disk diffusion tests accurately categorized beta-lactamase-producing strains and ampicillin-susceptible strains as being susceptible to the study drugs other than ampicillin. Ampicillin-resistant, beta-lactamase-nonproducing strains were relatively resistant to all seven study drugs, but the disk diffusion test did not always predict that resistance. The clinical relevance of the decreased susceptibility to various agents remains unclear, but to be conservative, all ampicillin-resistant, beta-lactamase-nonproducing strains might be assumed to be resistant to other beta-lactams. After excluding that small group of isolates, reliable susceptibility test results were obtained with lots of Haemophilus Test Medium that met quality assurance criteria. PMID- 8431014 TI - Neutralizing antibodies against the peptide antibiotic AS-48: immunocytological studies. AB - Antisera against the broad-spectrum peptide antibiotic AS-48 produced by Enterococcus faecalis were obtained from immunized rabbits. Appreciable antibody titers were obtained only after repeated immunization, suggesting a feeble antigenicity for AS-48. Upon incubation with AS-48, the antisera neutralized its bacteriolytic action on E. faecalis S-47, although the simultaneous addition of AS-48 and serum did not prevent lysis. Crude serum cross-reacted with outer envelope components of enterococci, although specific anti-AS-48 antibodies, purified by affinity chromatography, reacted only with AS-48-treated cells. Labelling with immunofluorescence and colloidal gold particles was carried out on sensitive and resistant bacterial species to determine the interaction of AS-48 with cell structures. PMID- 8431015 TI - High-level mupirocin resistance in Staphylococcus aureus: evidence for two distinct isoleucyl-tRNA synthetases. AB - Mupirocin resistance in Staphylococcus aureus results from changes in the target enzyme, isoleucyl-tRNA synthetase (IRS). Twelve strains of S. aureus comprising four susceptible (MICs < or = 4 micrograms/ml), four intermediate level-resistant (MICs between 8 and 256 micrograms/ml), and four highly resistant (MICs > or = 512 micrograms/ml) isolates were examined for their IRS content and the presence of a gene known to encode high-level mupirocin resistance. Ion-exchange chromatography of cell extracts showed a single IRS active peak in mupirocin susceptible strains, with 50% inhibitory concentrations (IC50s) of 0.7 to 3.0 ng of mupirocin per ml. In strains showing intermediate mupirocin resistance, similar single IRS activity peaks were observed, but these were less sensitive to inhibition, and the mupirocin IC50s for them were 19 to 43 ng/ml. Strains that were highly resistant to mupirocin displayed two distinct peaks; one was similar to that found with susceptible strains (IC50, 0.9 to 2.5 ng/ml), but an additional peak with an IC50 of 7,000 to 10,000 ng/ml was also observed. A strain cured of the plasmid encoding high-level mupirocin resistance lacked the resistant IRS peak. Restriction digests, produced by endonuclease NcoI, of total bacterial DNA isolated from the highly resistant strains hybridized with a mupirocin resistance gene probe, whereas DNA isolated from the intermediate level resistant and susceptible strains did not. These results demonstrate that two different IRS enzymes were present in highly mupirocin-resistant S. aureus strains. In strains expressing intermediate levels of resistance, only a chromosomally encoded IRS which was inhibited less by mupirocin than IRS from fully susceptible strains was detected. PMID- 8431016 TI - Multicenter evaluation of a broth macrodilution antifungal susceptibility test for yeasts. AB - Thirteen laboratories collaborated to optimize interlaboratory agreement of results of a broth macrodilution procedure for testing three classes of antifungal drugs against pathogenic yeasts. The activities of amphotericin B, flucytosine, and ketoconazole were tested against 100 coded isolates of Candida albicans, Candida tropicalis, Candida parapsilosis, Candida lusitaniae, Torulopsis (Candida) glabrata, and Cryptococcus neoformans. Two starting yeast inoculum sizes (5 x 10(4) and 2.5 x 10(3) cells per ml) were compared, and readings were taken after 24 and 48 h of incubation. All other test conditions were standardized. The resultant turbidities in all tubes were estimated visually on a scale from 0 to 4+ turbidity, and MIC-0, MIC-1, and MIC-2 were defined as the lowest drug concentrations that reduced growth to 0, 1+, or 2+ turbidity, respectively. For flucytosine, agreement among laboratories varied between 57 and 87% for different inocula, times of incubation, and end point criteria. Agreement was maximized (85%) when the lower inoculum was incubated for 2 days and the MICs were defined as 1+ turbidity or less. For amphotericin B, variations in test conditions produced much smaller differences in interlaboratory agreement. For ketoconazole, interlaboratory agreement was poorer by all end point criteria. However, MIC-2 endpoints distinguished T. glabrata as resistant compared with the other species. Overall, the studies indicated that readings from the lower inoculum obtained on the second day of reading result in the greatest interlaboratory agreement. In combination with data from previous multicenter studies (National Committee for Clinical Laboratory Standards, Antifungal Susceptibility Testing: Committee Report, Vol. 5, No. 17, 1988; M. A. Pfaller, L. Burmeister, M. S. Bartlett, and M. G. Rinaldi, J. Clin. Microbiol. 26:1437-1441, 1988; M. A. Pfaller, M. G. Rinaldi, J. N. Galgiani, M. S. Bartlett, B.A. Body, A. Espinel-Ingroff, R.A. Fromtling, G.S. Hall, C.E. Hughes, F. C. Odds, and A. M. SUgar, J. Clin. Microbiol. 34:1648-1654, 1990), these findings will be used by the National Committee for Clinical Laboratory Standards to develop a standardized method for in vitro antifungal susceptibility testing for yeasts. PMID- 8431017 TI - Prospective evaluation of effects of broad-spectrum antibiotics on gastrointestinal yeast colonization of humans. AB - This study evaluated the effects of broad-spectrum antibiotics on the gastrointestinal (G.I.) yeast flora of humans and correlated the findings with those obtained from a mouse model of G.I. colonization by Candida albicans. We prospectively studied 46 adult cancer patients who received one of five broad spectrum antibiotics (ceftriaxone, ceftazidime, ticarcillin-clavulanic acid, imipenem-cilastatin, and aztreonam) as therapy for infections. Quantitative examination of yeast colonization of stools was conducted at the baseline, at the end of antibiotic treatment, and 1 week after discontinuation of therapy. Antibiotics with anaerobic activity (ticarcillin-clavulanic acid) or high G.I. concentrations (ceftriaxone) caused a higher and more sustained increase in G.I. colonization by yeasts than did antibiotics with poor anaerobic activity (ceftazidime and aztreonam) or a low G.I. concentration (imipenem-cilastatin). These results were similar to those obtained with a mouse model of G.I. colonization by C. albicans that involved the same antibiotics. Hence, the mouse model may be useful for evaluation of yeast colonization of the human G.I. tract. PMID- 8431018 TI - Pharmacokinetics and protein binding of ceftriaxone during pregnancy. AB - The purpose of the present work was to study the pharmacokinetics and the protein binding (free fraction of the drug) of ceftriaxone (CTX) during pregnancy. Nine pregnant women (ages, 20 to 34 years) whose gestational ages ranged from 28 4/7 to 40 5/7 weeks were included. The diagnosis of infection was established in all cases; i.e., four women had chorioamnionitis and five women had pyelonephritis. The following triple antibiotic therapy was infused with the aim of achieving cure: CTX, 2 g once every 24 h (constant rate over 60 min); tobramycin, 3 mg/kg of body weight once every 24 h; and ornidazole, 1 g/day. Two series of blood samples were collected, i.e., during the first day of treatment (on day 1), to establish the primary pharmacokinetic profile of CTX, and at the plateau (on day 7), to evaluate a possible accumulation of the drug. This was an open, noncompartmental study, with each patient serving as her own control. Concentrations of total and unbound CTX in serum were measured by a high performance liquid chromatographic method. Pharmacokinetic analysis was done by a noncompartmental method. Data were compared by a Wilcoxon t test (a P value of < or = 0.05 was considered significant). Data were also compared with those obtained for healthy subjects who received similar treatments. (i) The tolerance to treatment was excellent, and in all cases patients had a complete remission without premature delivery. (ii) No accumulation of CTX was noted during the treatment, and the profiles of the drug determined at days 1 and 7 were not significantly different.(iii) The pharmacokinetic parameters measured in pregnant patients during the third trimester of pregnancy were similar to those measured in healthy subjects. (iv) Residual concentrations of total and unbound CTX measured at 24 h were greater than the MICs for allegedly susceptible organisms, both on day 1 and at steady state. (v) During the final 3 months of pregnancy, the dosage schedule of CTX (2-g infusion per day) required no particular adjustment (i.e., neither a loading dose nor any increase in the maintenance dose.) PMID- 8431019 TI - In vitro and in vivo antibacterial activities of E1077, a novel parenteral cephalosporin. AB - E1077, a new injectable cephalosporin with a broad antibacterial spectrum and potent antibacterial activity, was evaluated for its in vitro and in vivo antibacterial activities in comparison with those of cefpirome, cefuzonam, ceftazidime, and cefotaxime. E1077 showed broad in vitro antibacterial activity against gram-positive and gram-negative bacteria. Against methicillin-susceptible Staphylococcus aureus, E1077 was as active as cefpirome; the MIC for 90% of strains tested (MIC90) was 1.0 microgram/ml. Against methicillin-resistant S. aureus, E1077 was less active (MIC90, 64 micrograms/ml). For Enterobacter cloacae and Pseudomonas aeruginosa, E1077 was fourfold more active than cefpirome, with MIC90s of 1.0 and 16 micrograms/ml, respectively. For Proteus vulgaris, the MIC90 of E1077 was 32 micrograms/ml, which was fourfold greater than that of cefpirome. Against other gram-negative strains tested, the in vitro activity of E1077 was comparable to that of cefpirome. The broad antibacterial spectrum of E1077 was reflected by its in vivo efficacy against experimental septicemia caused by gram positive and gram-negative bacteria. Against S. aureus 90 and P. aeruginosa E7, E1077 had activity superior to those of the reference compounds; against most other bacterial strains, the efficacy of E1077 was similar to that of cefpirome. Levels of E1077 in plasma and tissue of mice were studied. At 15 min after a single subcutaneous administration, E1077 displayed high peak levels (mean, 31.8 +/- 3.1 micrograms/ml). These results indicate that the in vitro and in vivo efficacies of E1077 are similar to those of cefpirome except against P. aeruginosa and P. vulgaris. PMID- 8431020 TI - In vitro antimicrobial activity of benzoxazinorifamycin, KRM-1648, against Mycobacterium avium complex, determined by the radiometric method. AB - MICs of a newly developed benzoxazinorifamycin derivative, KRM-1648, for Mycobacterium avium complex (MAC) were determined by the BACTEC 460 TB system and compared with those of other known antimicrobial agents. The radiometric method gave a fast, accurate, and reproducible MIC for each antimicrobial agent. MICs of KRM-1648 for 30 strains of MAC (10 strains each of M. avium isolated from AIDS and non-AIDS patients and of Mycobacterium intracellulare isolated from non-AIDS patients) were measured. The MICs, ranging from 0.004 to 0.0625 microgram/ml, were the lowest of all tested drugs, including rifampin, rifabutin, streptomycin, kanamycin, isoniazid, ethambutol, ofloxacin, ciprofloxacin, sparfloxacin, and clarithromycin. The MICs were 2 to 512 and 1 to 32 times lower than those of rifampin and rifabutin, respectively. With rifampin and ethambutol, there were some differences between the MICs for M. avium isolated from AIDS patients (American) and those for M. avium from non-AIDS patients (Japanese). Moreover, appreciable differences between the MICs of some drugs against M. avium and M. intracellulare isolated from non-AIDS patients were found. Many strains of M. avium were more susceptible to ofloxacin than M. intracellulare, but, conversely, M. avium was more resistant to rifampin, streptomycin, ethambutol, and clarithromycin than M. intracellulare. PMID- 8431021 TI - Cloning of a Streptomyces clavuligerus DNA fragment encoding the cephalosporin 7 alpha-hydroxylase and its expression in Streptomyces lividans. AB - A 26-mer DNA probe was designed from N-terminal sequence data for the cephalosporin 7 alpha-hydroxylase (CH) of Streptomyces clavuligerus NRRL 3585 and used to screen a DNA library from this organism. The library was constructed in the lambda GEM-11 phage system. After plaque purification and reprobing, positive recombinant phages were chosen for further analysis. Characterization of the cloned DNA by restriction mapping and Southern hybridization showed that a 1.5-kb SalI fragment hybridized to the probe. Polymerase chain reaction assays using this fragment as a template and the probe as a primer indicated that the fragment carries the entire putative CH gene (cmcI). This was confirmed through the expression of CH enzymatic activity when the fragment was introduced into Streptomyces lividans. A putative beta-lactamase activity was detected in S. lividans. PMID- 8431022 TI - Comparison of population pharmacokinetic models for gentamicin in spinal cord injured and able-bodied patients. AB - Population pharmacokinetic models for gentamicin were developed by using data obtained from 29 spinal cord-injured patients and 11 able-bodied control patients. With a one-compartment model, the population parameters were clearance (CL), volume of distribution (V), and their associated variances. Parameter estimates were found by using the computer program NPEM and by the standard two stage (STS) method. NPEM uses a nonparametric approach incorporating the expectation maximization algorithm to evaluate a joint probability density function at 900 intersections over a bivariate grid. In contrast, the STS method requires conventional assumptions of normality for the underlying distributions. For NPEM, the mean CL was 97.6 ml/h/kg of body weight (coefficient of variation, 33.0% in the spinal cord-injured patients and 67.8 ml/h/kg +/- 28.2% in the able bodied patients; the mean V was 0.31 liter/kg +/- 32.3% in the spinal cord injured patients and 0.23 liter/kg +/- 15.8% in the able-bodied patients. For STS, the mean CL was 101.0 ml/h/kg +/- 37.5% in the spinal cord-injured patients and 65.0 ml/h/kg +/- 33.8% in the able-bodied patients; the mean V was 0.29 liter/kg +/- 34.0% in the spinal cord-injured patients and 0.21 liter/kg +/- 21.0% in the able-bodied patients. Although the means and variances found by NPEM and the STS method were similar, the NPEM analysis revealed that the distributions of CL and V, even after they were linked to weight, were positively skewed and kurtotic. The cumulative distribution functions for CL (P < 0.001) and V (P < 0.001) in spinal cord-injured patients were different from those in able bodied patients. Unique population models are required for the initial dosage selection for spinal cord-injured patients. Future approaches for developing population models should allow the linkage of structural parameters to multiple patient covariates. PMID- 8431023 TI - Universal precautions: providing a basis for HIV infection control guidelines. PMID- 8431024 TI - Humor, health and healing. AB - Research studies in the area of psychoneuroimmunology (PIN) are awakening health care professionals to the importance of positive emotions in aiding the healing process. The tumor movement in health care has led to its promotion in various ways. PMID- 8431025 TI - New insights on Goodpasture's syndrome. AB - Goodpasture's Syndrome is a rare illness that is often difficult to diagnose because of the large number of disease entities that can produce similar symptoms. With the discovery of antiglomerular basement membrane antibodies and antineutrophil cytoplasmic autoantibodies, plus the means to readily test for them, it is now possible to make an accurate and more rapid diagnosis of Goodpasture's Syndrome than has been possible in the past. Characteristics of Goodpasture's Syndrome include diffuse pulmonary hemorrhage, interstitial lung disease, anemia, and glomerulonephritis. Because of the potential for life threatening and rapidly progressive pulmonary hemorrhage, renal failure, or both, early and accurate diagnosis and treatment are imperative. Since the possibility of preserving renal function is minute if the renal disease is far advanced at the time of diagnosis, early intervention is crucial. Nursing care centered around the actual and potential problems that these patients experience is vital for preserving life and function. PMID- 8431026 TI - Technical considerations of therapeutic plasma exchange as a nephrology nursing procedure. AB - In the past, therapeutic plasma exchange (TPE) has had limited appreciation and lacked acceptance as a treatment modality. Jokingly, it has been referred to as a procedure looking for a disease because of seemingly broad historical applications to practice. In current clinical practice, TPE has earned its place as an aggressive therapeutic modality for treating a wide spectrum of diseases and/or syndromes. The acceptance of TPE has coincided with changes in equipment, technology, and the emergence of highly qualified professionals involved in performing the treatments. This article will describe these variables related to nephrology nurses becoming more involved in the use of TPE. PMID- 8431027 TI - Creation of a Spanish nephrological nursing accrediting course. AB - In 1989, the Spanish Association of Nephrological Nursing (Sociedad Espanola de Enfermeria Nefrologica--SEDEN) created a course directed to all graduates in nephrological nursing in Spain to answer a need for further training. This article details the objectives, methodology, and results of the Course for Accrediting Specialized Knowledge in Nephrological Nursing since it was created. PMID- 8431028 TI - Annotated bibliography: grant writing. AB - This is the first in series of annotated bibliographies on research topics that will appear in the ANNA Journal. The bibliographies have been prepared by members of ANNA's Research Special Interest Group. Each bibliography focuses on a particular topic and includes reviews of research books and articles published in nursing and allied health journals in recent years. The series is intended to assist nephrology nurse researchers in locating resources to plan and implement research studies and to communicate and implement research findings. The annotation for each item includes a full citation, a brief summary, and a categorization of the content level. The topic covered in this first bibliography is grant writing. Contributors to the grant writing bibliography were Nancy Hoffart, Janel Parker, and Nancy Seaby. The next installment will cover the research proposal, abstract writing, and the conceptual framework. Topics to be covered in future articles will include: (a) research proposal development and literature review; (b) poster preparation, abstract writing, and collaborative research; (c) instrument references, instrumentation, and reliability and validity; (d) research question, design and methods, and sampling; and (e) statistics and general nursing research texts. The following key was used in rating the content level for each citation: Basic/Introductory--For professionals who have no previous research background. Intermediate--For professionals who possess some knowledge of the research process and terminology, and have participated in some research projects. Advanced--For professionals who possess broad knowledge and experience with research projects. PMID- 8431029 TI - Preoperative peritoneal catheter abdominal marking. PMID- 8431030 TI - Familial hypercholesterolemia treated by plasma exchange and immunoadsorption. AB - IA clearly improved JL's HDL and LDL/HDL ratio because of its specificity, yet the extent of TC and LDL reduction per treatment was not as high as that obtained with TPE. Studies to achieve more efficient and specific extracorporeal lipid removal are in progress to help reduce the risk of CAD in FH patients and others. The continuity of procedural care and supportive needs provided by the nephrology nurses demonstrated a positive influence on J.L.'s acceptance of his familial genetic disorder and the prescribed chronic treatment regimen. PMID- 8431031 TI - Sodium polystyrene sulfonate: a cation exchange resin used in treating hyperkalemia. AB - Sodium polystyrene sulfonate is a cation exchange resin used in the treatment of nonlife-threatening hyperkalemia. Administered orally or rectally, the resin can effectively reduce serum potassium concentrations in the neonate as well as the elderly. Proper administration, assessment of drug effectiveness, and detection and prevention of potential adverse side effects of sodium polystyrene sulfonate are the responsibility of the nephrology nurse. PMID- 8431032 TI - Case management of the anemic patient: epoetin alfa--focus on ventricular function. AB - Chronic anemia frequently causes changes in cardiac function, particularly left ventricular function, that can lead to serious cardiovascular problems. Because Epoetin alfa corrects anemia, it may eliminate some of these problems or decrease their severity. By assessing cardiovascular function and monitoring response to Epoetin alfa, nurses can help patients achieve their optimal level of cardiac function. PMID- 8431033 TI - Primary hemangiopericytoma presenting as a Pancoast tumor. PMID- 8431034 TI - Is coronary reoperation without the pump an advantage? PMID- 8431035 TI - Warm blood cardioplegia: back to square one. PMID- 8431036 TI - Making some sENSE out of thoracoscopy. PMID- 8431037 TI - Valvular disease in the elderly: influence on surgical results. AB - Aortic valve disease in the elderly is primarily calcific stenosis with preservation of left ventricular function. In contrast, mitral valve disease in the elderly often is ischemic in nature with damage occurring to both valve and myocardium. The present study was undertaken to compare results of aortic (AVR) and mitral valve replacement (MVR) in the elderly and to ascertain predictors of poor outcome. Because patients who had concomitant coronary artery bypass grafting (CABG) are included (51% for AVR, 55% for MVR), patients who had isolated CABG were used as a comparison group. Between January 1, 1984, and June 30, 1991, 1,386 patients aged 70 years and older underwent CABG (n = 1,043), AVR (n = 245), or MVR (n = 98). The operative mortality rates were 5.3% for AVR, 20.4% for MVR, and 5.8% for CABG. Late follow-up of patients undergoing operation in 1984 and 1985 was available for 98% (231/237). Overall survival was comparable for all three groups through the first 5 years of follow-up (AVR, 68% +/- 8%; MVR, 73% +/- 8%; CABG, 78% +/- 3%). After 5 years, survival for patients having AVR and MVR was less than that for those having CABG. Patient age, sex, New York Heart Association functional class, concomitant CABG, prosthetic valve type, native valve pathology, and preoperative catheterization data were examined as possible predictors of outcome by multivariate logistic regression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431038 TI - Damus-Kaye-Stansel with cavopulmonary connection for single ventricle and subaortic obstruction. AB - Infants with single ventricle and transposition of the great arteries with or without aortic arch obstruction have a poor prognosis due in large part to the development of systemic outflow obstruction, a frequent consequence of pulmonary artery banding. Thus, the initial palliation and long-term treatment options are critical in terms of surgical choices and timing. We report our experience with 9 patients managed by neonatal pulmonary artery banding and early debanding, a Damus-Kaye-Stansel procedure, and either a modified Glenn shunt or a modified Fontan procedure. Some evidence of subaortic stenosis developed in every patient as manifested by a resting gradient across the systemic outflow tract (21.4 +/- 4.2 mm Hg), a small ventricular septal defect relative to the body surface area (1.57 +/- 0.39 cm2/m2), and a small ventricular septal defect relative to the aortic root cross-sectional area (0.70 +/- 0.04 cm2/m2). There were 1 early death and 1 late death after the Damus-Kaye-Stansel procedure. With the exception of 1 patient, the in-hospital course of the survivors was relatively uncomplicated. Two patients with levotransposition of the great arteries have required pacemakers. None of the survivors have residual systemic outflow obstruction. There is trivial or mild pulmonic insufficiency in 5 patients, which is not progressing. One patient had mild to moderate pulmonic insufficiency but died late presumably of an arrhythmia. We conclude that neonatal pulmonary artery banding coupled with planned early debanding, a Damus-Kaye-Stansel procedure, and cavopulmonary anastomosis is a relatively low-risk course for patients with this complex physiology. PMID- 8431039 TI - Atrioventricular canal defect: two-patch repair and tricuspidization of the mitral valve. AB - Between November 1978 and May 1991, a two-patch repair with tricuspidization of the left atrioventricular valve was performed in 104 patients with complete atrioventricular canal defect. Mean age was 12 months for the 68 patients who underwent primary repair and 22 months for the 36 patients who had previous pulmonary artery banding. Eleven patients died within 30 days of operation and 4 died late. Reoperation was carried out in 2 patients. Eighty-six patients were in sinus rhythm after operation. One patient required a permanent pacemaker for complete heart block. Follow-up data for 1 to 13 years are available in 80 of 89 survivors (90%). Actuarial survival at 13 years is 81% and event-free survival is 92%. Seventy-six patients are in New York Heart Association class I and 4 in class II. Postoperative echocardiogram of these patients showed minimal or no mitral regurgitation. The advantages of this technique are preservation of valve integrity, durable mitral valve repair, and rare reoperation or heart block even in younger patients. PMID- 8431040 TI - Double-lung transplantation in children: a report of 20 cases. The Joint Marseille-Montreal Lung Transplant Program. AB - In the last 3 1/2 years, we have performed 20 double-lung transplantations in children between 7 and 16 years old (mean age, 13 years). One patient had primitive bronchiolitis obliterans and the other 19, cystic fibrosis. Eight patients were operated on in an emergency situation, 7 of them requiring ventilator support before transplantation. The procedures were en bloc double lung transplantation in the first 11 patients with separate bronchial anastomoses in 10, and sequential bilateral lung transplantation in the later 9 patients. There were no operative deaths. Two patients died in the hospital on postoperative days 37 and 73, and there were four late deaths, which were due to infection, rejection, and bronchiolitis obliterans. The acceptable incidence of airway complications, the improvement in lung function of survivors, and the acceptable midterm survival make double-lung transplantation an acceptable alternative to heart-lung transplantation in children. However, in very small children, heart-lung transplantation may be preferable because of the size of the airway anastomoses at risk. PMID- 8431041 TI - Retrograde continuous warm blood cardioplegia: maintenance of myocardial homeostasis in humans. AB - Recent clinical reports have suggested that continuous delivery of oxygenated warm blood cardioplegia through the coronary veins (retrograde cardioplegia) produces good myocardial preservation during aortic cross-clamping. No data exist, however, about actual myocardial metabolism/homeostasis during retrograde warm blood cardioplegia. We studied 100 consecutive patients undergoing coronary artery bypass grafting, aortic valve replacement, or both who received retrograde continuous warm blood cardioplegia (4:1 dilution) during aortic cross-clamping for 54 to 174 minutes. We measured pH, oxygen tension, carbon dioxide tension, HCO3, base excess, and oxygen content of the inflow cardioplegia and the blood egressing from coronary arteries during each arteriotomy for bypass grafting (arteries act as postcapillary veins with retrograde cardioplegia) or the left and right coronary orifices during aortic valve replacement. We also measured these variables from the coronary sinus effluent 1 minute after release of the aortic cross-clamp. Retrograde cardioplegia flow ranged from 50 to 250 mL/min (mean flow, 150 mL/min). All patients were maintained at normothermia during bypass. A total of 460 samples were analyzed (4.6 per patient). Neither the duration of aortic cross-clamping nor the artery sampled affected myocardial blood gases. The pH dropped from 7.41 +/- 0.05 for the inflow cardioplegia to 7.32 +/- 0.1 when sampled from coronary arteries, and the oxygen tension fell from 181 +/- 25 to 28 +/- 5 mm Hg, respectively. Carbon dioxide tension rose from 31.0 +/- 4.1 to 41.4 +/- 9.8 mm Hg. Coronary sinus blood gases 1 minute after cross-clamp removal showed no acidosis or oxygen debt.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431042 TI - Optimal pleurodesis: a comparison study. AB - With the resurgence of thoracoscopy, there is renewed interest in less invasive methods of pleurodesis. We wished to compare in an animal model a variety of methods suggested in reports. The purpose of the study was to rank the effectiveness of each procedure against the standard mechanical pleurodesis. Twenty-five mongrel dogs (weight, 25 to 35 kg) underwent bilateral thoracotomy. Each animal was randomly assigned to receive two of the following methods of pleurodesis: tetracycline, talc, mechanical abrasion, neodymium: yttrium-aluminum garnet (Nd:YAG) laser (Hereus Inc, E. Rutherford, NJ) photocoagulation, and argon beam coagulator (ABC) (Beacon Lab, Bloomfield, CO) electrocoagulation of the parietal pleura. At evaluation at 30 +/- 2 days, the efficacy of pleurodesis was graded on a scale of 0 to 4, with 0 representing a complete absence of pleural symphysis and 4 the adhesion of more than one lobe to both the chest wall and mediastinum. Mean grade and standard deviation of each method were: talc, 3.0 +/- 0.67; mechanical, 3.0 +/- 0.82; tetracycline, 2.3 +/- 1.4; ABC, 1.5 +/- 0.97; and Nd:YAG laser, 0.7 +/- 0.95. Both the talc and mechanical methods were superior to either the Nd:YAG laser or the ABC (p < 0.01). In this study, neither the Nd:YAG laser nor the ABC proved efficacious in producing pleurodesis. Talc poudrage is the only method of pleural symphysis comparable with mechanical abrasion. PMID- 8431043 TI - Intrapleural quinacrine instillation for recurrent pneumothorax or persistent air leak. AB - From 1982 to 1990, 27 patients with recurrent pneumothorax or persistent air leak (28 episodes) underwent pleurodesis with intrapleural administration of quinacrine, according to a standardized scheme. A first evaluation was done about 1 month after the intervention. In August 1990, all patients were invited for a second check-up. In 4 patients quinacrine plasma concentrations were determined. There was one early failure. No late recurrences were observed. Neither serious nor late complications were seen with our low-dose regimen. Transient fever was the only constant side effect. In contrast to other chemicals proposed for pleurodesis, quinacrine did not cause major pain. Only very low quinacrine plasma concentrations (peak, < 10 ng/mL) were found. In conclusion, chemical pleurodesis with quinacrine can be considered a safe and effective treatment. The number of administrations as well as the dosage are important to prevent morbidity and recurrence. PMID- 8431044 TI - Secondary spontaneous pneumothorax. AB - To assess the clinical manifestations and therapy of secondary spontaneous pneumothorax (SSP), 123 episodes of SSP in 67 patients were retrospectively reviewed and were compared with 254 episodes of primary spontaneous pneumothorax in 130 patients. The major underlying lung diseases associated with SSP were emphysema (22 patients) and tuberculosis (21 patients). The average age of patients with SSP was 66.8 years, and the most common symptom was dyspnea. The average arterial oxygen tension at onset of SSP was 61.1 +/- 12.1 mm Hg (mean +/- standard deviation), which was lower than that of patients with primary spontaneous pneumothorax (p < 0.01). The recurrence rate of open thoracotomy with pleural abrasion was 12.5% (3 of 24 episodes), which was not lower than that of thoracostomy tube drainage with chemical pleurodesis using tetracycline (recurrence rate, 18.8%) (p > 0.5). We concluded that considering the high age of the patients, the presence of underlying lung diseases, and the increased operative risk, thoracostomy tube drainage rather than open thoracotomy was preferred as the first choice of therapy for SSP. PMID- 8431045 TI - Continuous intercostal nerve block versus epidural morphine for postthoracotomy analgesia. AB - Twenty patients undergoing elective thoracotomy were randomized into two groups, receiving either lumbar epidural morphine (n = 10) or continuous extrapleural intercostal nerve block (n = 10). Subjective pain relief was assessed on a linear visual analogue scale. Pulmonary function (peak expiratory flow rate, forced expiratory volume in 1 second, and forced vital capacity) was measured on the day before operation and daily for 4 days after operation. Pulse oximetry monitoring was used to determine the incidence of hypoxemia. No significant difference was observed between the groups concerning pain relief (except at 28 hours, in favor of the intercostal nerve block group), respiratory performance, or arterial oxygen saturation. Vomiting, pruritus, and urinary retention occurred only in the epidural group, whereas nausea occurred significantly less frequently in the extrapleural group. We conclude that after thoracotomy continuous extrapleural intercostal nerve block is as effective as lumbar epidural morphine in reducing postoperative pain and restoring pulmonary mechanics. Because of the significantly lower complication rates we favor continuous extrapleural intercostal nerve block for postthoracotomy analgesia. PMID- 8431046 TI - Continuous intercostal analgesia with 0.5% bupivacaine after thoracotomy: a randomized study. AB - This study was undertaken to evaluate the effectiveness of 0.5% bupivacaine (360 mg/day) as a continuous infusion through an indwelling intercostal catheter inserted intraoperatively in the management of pain after thoracotomy. Eighty-six patients were randomized into three groups: group 1 = intercostal bupivacaine, group 2 = intercostal saline solution, and group 3 = fixed-schedule intramuscular buprenorphine. Supplementary buprenorphine was given as required. Pain and pulmonary function were assessed throughout the first 5 days after operation. Pain score was lower in group 1 than in group 2 for the first 8 hours after operation (p < 0.02). During the first 3 postoperative days, mean postoperative pain scores of 5 or more were recorded in 9% of group 1 patients versus 40% of group 2 patients (p < 0.05) and 13% of group 3 patients (not significant). Total doses of buprenorphine were lower in groups 1 and 2 than in group 3 (p < 0.001). No between-group differences in pulmonary function were observed. Respiratory complications occurred in no patients in groups 1 and 3 versus 5 in group 2 (p < 0.05). Continuous intercostal bupivacaine provided similar early pain control as compared with fixed-schedule narcotics but induced better analgesia with fewer complications than on-demand narcotics alone (group 2). PMID- 8431047 TI - Homograft aortic root replacement for destructive prosthetic endocarditis. AB - Prosthetic aortic valve endocarditis with extensive destruction of the aortic root, annular abscess formation, and left ventriculoaortic discontinuity was seen in 3 patients, with aorta to left atrial fistula formation in 2. Homograft aortic root replacement with use of the anterior mitral leaflet of the aortic root to repair the fistula was used successfully in all 3 patients. Their case reports are discussed to highlight the use of the homograft aortic root in these complicated cases, and to report the occurrence of aorto-left atrial fistula in prosthetic valve endocarditis. PMID- 8431048 TI - Regulation of acute phase response after cardiopulmonary bypass by immunomodulation. AB - The object of this prospective, randomized trial was to study the dysregulation effects of cardiopulmonary bypass on the synthesis pattern of interleukin-1, tumor necrosis factor, and interleukin-6, which have been identified as the key mediators of acute phase response. In addition, the counterregulation achieved by administration of indomethacin, which blocks the downregulating mediator prostaglandin E2, or indomethacin combined with thymopentin, which enhances T lymphocytic reactivity, was investigated. Sixty patients who had undergone open heart operations were included in the study. These patients were divided into three groups: group A (n = 20) received both indomethacin and thymopentin, and group C (n = 20) served as control. In control patients interleukin-1 and tumor necrosis factor synthesis were suppressed postoperatively. This effect was significantly counteracted by indomethacin with no further improvement by adding thymopentin. Interleukin-6 synthesis increased in all groups. Although indomethacin treatment alone had little effect on this phenomenon, additional administration of thymopentin significantly reduced elevated interleukin-6 synthesis. Corresponding differences in clinical outcome could not be detected due to small patient numbers. This study was, however, able to demonstrate that an immunomodulatory therapy can influence alterations in immune mechanisms after cardiopulmonary bypass. PMID- 8431050 TI - Hyperbaric oxygenation for arterial air embolism during cardiopulmonary bypass. AB - The incidence of systemic air embolism during cardiopulmonary bypass is estimated to be 0.1%. However, the vast majority of instances are unreported and quietly ignored. The result may be disability or death. The control of air embolism obviously lies in prevention. The definite and specific treatment of this complication is hyperbaric oxygen. We report 6 patients referred to our institute because of air embolism during cardiopulmonary bypass. Of the 4 patients in whom hyperbaric oxygen therapy was delayed for 17 to 20 hours, 2 showed partial neurological improvement, as opposed to the success of hyperbaric oxygen therapy in the 2 patients in whom the delay was minimal. We conclude that as soon as the proposed open heart operation has been completed and there is an indication that air embolism has occurred, the patient should be treated with hyperbaric oxygen as quickly as possible, even before neurologic manifestations of cerebral ischemia appear. PMID- 8431049 TI - Cardiac preconditioning does not require myocardial stunning. AB - Efforts to minimize the deleterious effects of intraoperative myocardial ischemia reperfusion (I/R) injury have been primarily directed at optimizing cardioplegic solutions and altering reperfusion conditions. Classically, myocardial I/R has been associated with cardiac mechanical dysfunction ("stunning"). Recently, we reported an alpha 1-adrenergic receptor-mediated mechanism of paradoxical myocardial protection against I/R insult induced by a prior episode of transient ischemia, a phenomenon known as "ischemic preconditioning." Myocardial stunning resulting from transient ischemia has previously been associated with ischemic preconditioning, prompting intuitively negative bias against the clinical application of this phenomenon. The purpose of this study was to determine whether transient ischemia of insufficient duration to cause prolonged mechanical dysfunction (stunning) can induce favorable cardiac preconditioning. Isolated perfused rat hearts were allowed to equilibrate for 8 minutes and were then subjected to either 2 minutes of global, normothermic transient ischemia or 2 minutes of 50 mumol/L phenylephrine infusion. A stabilization period of perfusion lasting 10 minutes after the termination of transient ischemia or phenylephrine infusion was followed by a standard I/R challenge (20 minutes of global, normothermic ischemia; 40 minutes of reperfusion). Ventricular function (measured as developed pressure in millimeters of mercury) recovered rapidly after transient ischemia such that no impairment was present before the subsequent standard I/R challenge. Phenylephrine treatment was associated with no residual inotropy before I/R challenge. Control hearts were subjected only to the standard I/R challenge after an initial 20-minute equilibration period. After reperfusion control hearts exhibited 54.4% recovery of initial left ventricular developed pressure. Transient ischemia- and phenylephrine-preconditioned hearts recovered 84.4% (p < 0.01) and 82.4% (p < 0.01), respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431051 TI - Noninvasive hemodynamic assessment of the internal mammary artery in myocardial revascularization. AB - Using transthoracic B-mode imaging and Doppler spectrum analysis it was found that the luminal diameter of the internal mammary artery and its hemodynamics were not significantly different among 15 preoperative patients (64 +/- 10 years) who underwent myocardial revascularization using the left internal mammary artery and young and older control groups (25 +/- 3 years and 61 +/- 9 years, respectively). These data indicate that older age does not significantly adversely influence the degree of intimal thickening and compliance in the internal mammary artery. Doppler spectrum analysis of the internal mammary artery in the patients who were operated on revealed conversion from a triphasic systolic waveform preoperatively to a unidirectional combined systolic/diastolic waveform at 1 week and 2 and 6 months postoperatively, characterized by a significant increase in the diastolic blood flow velocity and a significant decrease in the systolic blood flow velocity and the pulsatility and resistance indices. This study indicates that transthoracic B-mode imaging and Doppler spectrum analysis are promising noninvasive techniques in the preoperative assessment of internal mammary artery morphology and physiology. In addition, Doppler spectrum analysis can also be used in the long-term serial assessment of the internal mammary artery conduit after myocardial revascularization. PMID- 8431052 TI - Role of autogenous tissue factors in hemolysis during cardiopulmonary bypass operations. AB - Pericardial fluid has been implicated as a causative factor in hemolysis during cardiopulmonary bypass operations. Preoperative blood samples were obtained from 10 patients undergoing coronary artery bypass grafting for ischemic myocardial disease. Whole blood samples were separately incubated with autogenous pericardial fluid, pericardium, pleura, vein, skeletal muscle, and fat harvested during the operative intervention. The plasma fraction was separated by centrifugation and assayed for serum free hemoglobin. Statistical analysis was accomplished by the Bonferroni technique to adjust for multiple comparisons. Pericardial fluid-induced hemolysis was least (20.7 mg/dL). Pleura and muscle contributed significantly to the serum free hemoglobin level (56.3 and 112.3 mg/dL, respectively; p < 0.05). Pericardium, vein, and fat did not cause significant elevations of the serum free hemoglobin level. Postbypass hemolysis is an important management consideration that may be minimized by delicate tissue manipulation and attention to minimizing tissue trauma. Avoidance of aspiration of pericardial fluid into the autotransfusion system is not supported. PMID- 8431053 TI - Preimplantation alteration of adenine nucleotides in cryopreserved heart valves. AB - To assess the initial metabolic phase of cellular injury from cardiac valve processing, high-energy phosphate concentrations were analyzed in valve leaflets subsequent to critical processing steps. Using a porcine model, valves were processed in a manner identical to human homografts, with 58 randomly assigned to five groups representing distinct preparation phases. Group I (controls) sustained 40 minutes of warm ischemia concluded by liquid nitrogen immersion. Remaining groups similarly endured 40 minutes of ischemia, but were subsequently prepared according to stepwise design: II, warm ischemia + 24 hours of 4 degrees C ischemia; III, warm ischemia + 24 hours of 4 degrees C antibiotic disinfection; IV, warm ischemia + 24 hours at 4 degrees C (without antibiotics) + cryopreservation (-1 degrees C/min cryoprotected freezing); and V, warm ischemia+disinfection+cryopreservation. At each regimen's conclusion leaflet extracts were assayed by high-performance liquid chromatography for high-energy adenine nucleotides (adenosine triphosphate, adenosine diphosphate, adenosine monophosphate) and catabolites. A 47% and 86% decrease in cellular adenosine triphosphate level was observed in group III and group V leaflets, respectively. The level of total adenine nucleotides was maintained up to cryopreservation; thereafter a 74% decrease was noted. Catabolite analysis confirmed incomplete degradation of adenine nucleotides indicating cellular metabolic resilience throughout standard homograft preparation in valves previously exposed to 40 minutes of warm ischemia. PMID- 8431054 TI - Interstitial pH during myocardial preservation: assessment of five methods of myocardial preservation. AB - We investigated changes in myocardial pH during cardioplegic arrest with five methods of preservation at 15 degrees +/- 1 degree C. Twenty-five dogs were subjected to cardiopulmonary bypass for 150 minutes. Group I (control) had hypothermia only. Group II received THAM-buffered blood cardioplegia, group III a bicarbonate-buffered blood cardioplegic solution, group IV infusions of hyperkalemic blood, and group V oxygenated St. Thomas 2 solution. After 120 minutes of ischemia, interstitial pH in group I was markedly depressed (6.4 +/- 0.07; p < 0.01). The pH in groups II and IV was well maintained (7.23 +/- 0.05 and 7.27 +/- 0.07) and differed significantly (p < 0.05) from that of the remaining groups. The pH in groups III and V was less well maintained (7.14 +/- 0.02 and 7.01 +/- 0.05), with no significant difference (p > 0.05) between these two groups. Postreperfusion functional recovery after 45 minutes was 24% +/- 6% in group I, 92% +/- 3% in group II, 82% +/- 5% in group III, 84% +/- 4% in group IV, and 66% +/- 6% in group V. Creatine kinase levels were significantly (p < 0.01) increased and ultrastructural damage was more prominent in group I compared with the remaining groups. Myocardial water content significantly increased in all groups. We conclude that a strongly buffered blood-based cardioplegic solution is more effective in preventing interstitial acidosis during moderate hypothermia and that maintenance of an optimal tissue pH plays an important role in postischemic functional recovery. PMID- 8431055 TI - Autologous vein supported with a biodegradable prosthesis for arterial grafting. AB - To evaluate the potential of a supporting, compliant, biodegradable prosthesis to function as a temporary protective scaffold for autologous vein grafts in the arterial circulation, we implanted vein grafts into the carotid arteries of rabbits, either with (composite grafts) or without (control grafts) such a supporting prosthesis, and evaluated them up to 6 weeks. The control vein grafts showed edema and severe medial disruption with infiltration of polymorphonuclear cells on day 1. Over the study, irregular fibrocyte formation resulted in the formation of a fibrotic vein wall. In contrast, the composite vein grafts showed preservation of smooth muscle cell layers and elastic laminae with a minor inflammatory response. Regular proliferation of fibroblasts, which in some areas were circularly oriented, was observed. We conclude that a supporting, compliant, biodegradable prosthesis can function as a protective scaffold for vein grafts in the arterial circulation, thus reducing damage to the vein graft wall and allowing gradual arterialization. PMID- 8431056 TI - Safe pulmonary preservation for 12 hours with low-potassium-dextran solution. AB - The function of porcine left lung allografts was studied after perfusion with (150 mL/kg) and storage for 12 hours in a 4 degrees to 6 degrees C low-potassium dextran solution (Perfadex; Kabi Pharmacia AB, Uppsala, Sweden). After a left lung transplantation, an artificial lung in the form of venoarterial extracorporeal membrane oxygenation was established. The artificial lung has a "biological" heparin-coated surface (Carmeda AB, Stockholm, Sweden), and there is no need for systemic anticoagulation. Immediately thereafter, pneumonectomy of the normal right lung was done. All the animals were weaned from the artificial lung within 1 hour after the pneumonectomy. Six animals were followed up for 24 hours. They were in good condition throughout the 24-hour observation period with arterial oxygen tensions around 200 mm Hg (inspired oxygen fraction = 0.4) and arterial carbon dioxide tensions around 40 mm Hg. This study demonstrates a reliable method for continuous evaluation of the function of a transplanted lung immediately after transplantation and over the ensuing postoperative period. Safe 12-hour lung preservation can be obtained with the low-potassium-dextran solution Perfadex. PMID- 8431057 TI - Early cardiac allograft rejection is independent of regional myocardial blood flow. AB - Noninvasive telemetric monitoring of canine heterotopic cardiac allograft unipolar peak-to-peak amplitude (UPPA) has permitted prospective surveillance for rejection; moreover, this technique is able to reliably detect rejection before the development of histologic evidence of myocyte necrosis. This study was performed to determine whether early cardiac allograft rejection and the accompanying decline in allograft UPPA were associated with alterations in regional myocardial blood flow (RMBF). Seven heterotopic, intrathoracic canine cardiac transplantations were performed using triple-drug immunosuppression. Native hearts and allografts were instrumented with right ventricular and left ventricular epicardial screw-in electrodes connected to subcutaneous telemeters. Daily measurement of native and graft UPPA was performed; using radioactive microspheres, native and graft RMBF were determined during the control period and when UPPA had declined by 15%, 30%, and 45%. Graft histologic status was determined by endomyocardial biopsy at the time of RMBF determination. Mean duration of the study was 19.7 +/- 3.9 days. Rejection was documented in all animals. The UPPA was stable in native hearts; UPPA declined in the allografts after the onset of rejection. A biphasic change in allograft blood flow was seen. Initially RMBF increased as UPPA declined; a 30% to 45% reduction in UPPA was associated with a 41% increase in RMBF (p = 0.028 versus allograft control). Subsequently, a significant decline in blood flow was observed for reductions in UPPA greater than 45% (0.68 +/- 0.44 versus 1.07 +/- 0.47 mL.g-1 x min-1 for a 30% to 45% decline in UPPA; p = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431058 TI - Plasma endothelin levels and surgically correctable pulmonary hypertension. AB - To know the changes in plasma endothelin of patients with pulmonary hypertension, we studied 32 patients with valvular heart disease. Among them, 22 patients had pulmonary hypertension (group I) and 10 had pulmonary arterial pressures in the normal range (group II). Plasma endothelin-1 concentrations of the patients in group I were significantly greater than those of the patients in group II (p < 0.05). No significant difference in plasma endothelin-3 concentrations existed between the two groups. Cardiac output and pulmonary capillary wedge pressure had a linear correlation with plasma endothelin-1 levels. There was also a significant correlation between plasma endothelin-1 levels and hemodynamic indicators of severity of pulmonary hypertension, such as mean pulmonary arterial pressure and pulmonary vascular resistance (p < 0.05). All patients in this study underwent surgical procedures for the correction of valvular lesions. All patients in group I showed a decrease in pulmonary arterial pressures, and their plasma endothelin-1 levels decreased from 3.84 +/- 0.20 pg/mL to 1.66 +/- 0.07 pg/mL (p < 0.05), whereas the plasma endothelin-3 levels had only slight variation from 0.64 +/- 0.11 pg/mL to 0.75 +/- 0.06 pg/mL (p > 0.05) between the preoperative and the postoperative stages. The results demonstrated that plasma endothelin-1 rather than endothelin-3 had a role in pulmonary hypertension. Several pieces of evidence pointed out that endothelin-1 functioned as a reactive mediator during vasoconstriction in the case of pulmonary hypertension rather than as a triggering factor of pulmonary hypertension. PMID- 8431059 TI - Primary closure for infected dehiscence of the sternum. AB - I propose a new irrigation-suction system to achieve primary closure of the sternum in cases of postoperative infected dehisced sternotomy. Of 16 cases, I had no treatment failures, no recurring infections, and no patient deaths after 1 to 8 years of follow-up. The new system entails retrosternal and superficial sets of tubes, both in double-staggered position, with primary closure of the sternum and of the skin. Skin or muscle flaps are avoided, and the stability of the chest cage is maintained. Hospitalization time is 14 to 18 days. PMID- 8431060 TI - Effect of methylprednisolone and prostacyclin on bronchial perfusion in lung transplantation. AB - In an experimental investigation using modified unilateral lung transplantation in pigs, the effects of systemic administration of methylprednisolone and prostacyclin on bronchial mucosal blood flow were assessed. Laser Doppler velocimetry (LDV) and radioisotope studies using radiolabeled erythrocytes (RI) were employed to measure blood flow at the donor main carina and upper lobe carina after 3 hours of reperfusion. The recipient carina was used as a reference point. Five groups of 6 animals each were studied. Group I served as control. In group II, methylprednisolone (20 mg/kg) was administered to the recipient. In group III, prostacyclin (4 ng.kg-1.min-1) was given to the recipient, and in group IV, prostacyclin (100 micrograms intravenously) was administered to the donor. In group V, prostacyclin was given to the recipient and the donor animals as in groups III and IV, respectively. In group I, bronchial blood flow at the donor main carina was 37.6% +/- 2.2% (LDV) and 44.1% +/- 14.8% (RI) of reference blood flow. No significant differences were found between the controls and groups II, III, and IV. In group V, bronchial blood flow was markedly increased both at the donor main carina (LDV, 39.8% +/- 6.2%, p = 0.12; RI, 55.7% +/- 11.4%, p < 0.2) and the donor upper lobe carina (LDV, 65.8% +/- 5.4%, p < 0.05; RI, 76.8% +/ 21.3%, p < 0.2). We conclude that systemic administration of prostacyclin to the donor and recipient results in marked improvement of bronchial blood flow and may reduce the incidence of bronchial complications after lung transplantation. PMID- 8431061 TI - Pressure-volume relationship of the fetal lamb heart. AB - In contrast to the adult heart, the fetal heart reportedly has little functional reserve. With increased clinical emphasis on fetal cardiac diagnosis, neonatal surgery, and the potential for future fetal cardiac intervention, it is essential that we better understand fetal cardiac function. Therefore, to demonstrate the extent of fetal cardiac preload reserve, we studied 10 fetal lambs using an isolated, isovolumic, blood-perfused heart preparation. We maintained constant afterload, inotropic state, coronary blood flow, heart rate, and perfusate blood gas values. As left ventricular (LV) volume (preload) was incrementally increased, LV end-diastolic pressure and LV peak systolic pressure were recorded. Linear regression analysis demonstrated that increases in LV developed pressures were predicted by the LV volume, demonstrating the presence of the Frank-Starling mechanism in each case. The plateau of the Starling pressure-volume curve occurred at an LV end-diastolic pressure of 12.5 +/- 4.79 mm Hg (95% confidence interval, 9.07 to 15.9 mm Hg), lower than the plateau expected in the adult heart. This implies that, in the management of fetal and immature neonatal hearts, preload reserve plays an important but limited role in cardiac reserve. PMID- 8431062 TI - Surgical management and radiological characteristics of bronchogenic cysts. AB - Forty-two patients with bronchogenic cysts were treated over a 30-year period (1962 to 1991). The location was mediastinal in 37 and intrapulmonary in 5. Cysts were symptomatic in 21 patients (50%) and complications occurred in 11 (26%). The complications included infection in 5 patients, hemorrhage into the cyst in 2 patients, dysphagia due to esophageal compression in 2, adenocarcinoma arising from a bronchogenic cyst in an 8 1/2-year-old girl, and an esophagobronchopleurocutaneous fistula as a result of previous incomplete resection in 1 patient. Magnetic resonance imaging has been found to provide specific diagnostic information about bronchogenic cysts. All but 2 patients were treated with complete excision. One patient was managed by observation and another had drainage of the cyst by mediastinoscopy. Complications of treatment occurred in only 2 patients. One had a minor wound infection and the other had Clostridium difficile enterocolitis. Only 4 patients were lost to follow-up. No late complication or recurrence developed in those patients having complete excision. We recommend complete excision in most instances to confirm the diagnosis, relieve symptoms, and prevent complications. PMID- 8431063 TI - De Vega's semicircular annuloplasty for tricuspid valve regurgitation. AB - Moderate to severe functional tricuspid regurgitation was found in 26% of cardiac surgical patients with mitral or aortic valvular disease at Tri-Service General Hospital in Taiwan. Almost all patients were able to receive de Vega's annuloplasties. After a mean follow-up period of 20 months, none of the 63 patients had moderate or severe tricuspid regurgitation. There was no heart block or right atrial thrombosis; the single late death was not related to the heart disease. De Vega's tricuspid annuloplasty is considered to be a safe, effective, and durable procedure in the treatment of functional tricuspid regurgitation. Compared with tricuspid valve replacement and other types of annuloplasty, the de Vega is the first choice here. PMID- 8431064 TI - Reoperative coronary artery bypass grafting without cardiopulmonary bypass. AB - Between June 1979 and January 1992, 46 men and 13 women aged 35 to 81 years (mean, 58 years) underwent reoperative coronary artery bypass grafting without cardiopulmonary bypass. Isolated reoperative circumflex bypass was performed through a left thoracotomy, and reoperative bypass to the right coronary artery and left anterior descending coronary systems was through a median sternotomy. Complete revascularization was the goal in all patients. Saphenous vein grafts were placed to the right coronary artery (n = 21), circumflex artery (n = 11), and left anterior descending artery (n = 24), and 14 internal thoracic artery to left anterior descending artery bypass grafts were performed. The overall mortality rate was 3.4% (2 deaths). Postoperative morbidity included myocardial infarction in 1 patient and pleuropulmonary complications in 6. No patient was reexplored for hemorrhage, and 19 patients required no blood products. Twenty patients underwent repeat coronary angiography, and 18 of 20 grafts placed without cardiopulmonary bypass were patent. At a mean follow-up interval of 42.2 months 35 of 50 evaluable patients were in functional class I or II. In selected patients, reoperative coronary artery bypass grafting can be performed without cardiopulmonary bypass with a low perioperative morbidity and mortality rate, satisfactory graft patency rates, and good long-term symptomatic improvement. PMID- 8431065 TI - Pentoxifylline decreases cyclosporine-induced renal endothelin release and vasoconstriction. AB - Cyclosporine (CSA) causes an acute vasoconstriction of renal artery and a significant increase in renal endothelin release. Pentoxifylline, a vasodilator, has been suggested to prevent CSA toxicity. To study the effect of pentoxifylline treatment on CSA-related vasoconstriction and endothelin release, a model of renal autoperfusion in the dog was used. Oral pentoxifylline at the dose of 400 mg three times daily for 3 days was given to 15 dogs. Pure powder CSA (10 mg) was injected into the isolated renal artery perfused at constant flow; changes in perfusion pressure reflected variations in vascular resistance. In the pentoxifylline-treated group (15 dogs), the infusion of CSA caused an average increase of 27 +/- 8 mm Hg in renal perfusion pressure, compared with 60 +/- 10 mm Hg in a control group of 8 untreated animals (p < or = 0.05). Plasma concentration of endothelin in the renal vein increased from an average of 1.2 +/ 0.2 pg/mL before to 2.4 +/- 0.5 pg/mL after CSA administration (p < or = 0.05) in the control group, whereas it did not change significantly in the pentoxifylline-treated group. Thus, oral pretreatment with pentoxifylline significantly decreased the renal vasoconstriction and endothelin release due to CSA administration. PMID- 8431066 TI - Dynamic cardiomyoplasty in chronic left ventricular failure: an experimental model. AB - Dynamic cardiomyoplasty continues to attract interest as a therapeutic option in the management of heart failure. In a large animal model of ischemic heart failure, we have compared dynamic cardiomyoplasty with both adynamic cardiomyoplasty and a control group. Heart failure was induced by coronary artery ligation in sheep, and under the same anesthetic dynamic cardiomyoplasty (n = 5), adynamic cardiomyoplasty (n = 4), or no further procedure was performed (n = 5). After recovery the animals were housed for a further 3 months. The dynamic cardiomyoplasty underwent a recognized muscle transformation protocol during this period. At terminal studies, the animals were hemodynamically assessed, both under baseline conditions and after colloid volume loading. The data at baseline were compared with unpaired t tests, and the function curves created by volume loading were compared by analysis of variance. Although the changes at baseline were small, there were highly significant improvements in the function curves in the dynamic cardiomyoplasty group when the stimulators were turned on compared with stimulators off (p = 0.005) for cardiac output; p = 0.035 for left ventricular end-diastolic pressure; p = 0.002 for pulmonary artery capillary wedge pressure; p = 0.004 for stroke volume; and p = 0.003 for cardiac power). There were also significant improvements in indices of cardiac performance when the dynamic cardiomyoplasty group was compared with both the control and adynamic cardiomyoplasty groups. We conclude that there is experimental evidence that cardiomyoplasty augments cardiac function in a model of chronic left ventricular failure. PMID- 8431067 TI - Late results after triple-valve replacement with various substitute valves. AB - The purpose of this study was to determine what influence various combinations of mechanical and bioprosthetic valves in the aortic, mitral, and tricuspid positions had on late morbidity and mortality of 40 hospital survivors of triple valve replacement. At operation the patients ranged in age from 27 to 69 years; 73% were women. The mean postoperative follow-up interval was 8.3 years, with a total follow-up of 331 years (100% complete). At 12 months after operation, functional class decreased from 3.3 to 1.6 (p < 0.05), cardiac index increased from 2.0 to 2.6 L.min-1 x m-2 (p < 0.05), and pulmonary artery pressures decreased from 59/27 to 40/17 mm Hg (p < 0.05). There were no differences in preoperative variables between groups. Actuarial survival for the 40 patients (exclusive of 30-day or in-hospital mortality, which was 31%) was 78% and 74% at 5 and 10 years. At the same milestones, freedom from reoperation was 96% and 54%, freedom from combined thromboembolism and anticoagulant-related hemorrhage was 68% and 56%, and freedom from all late valve-related morbidity and mortality was 64% and 25%. Comparison of the patients with two or more mechanical prostheses with the patients having two or more bioprostheses indicated no significant differences in actuarial freedom from late death, thromboembolic events, or anticoagulant-related hemorrhage. However the actuarial freedom from reoperation in the groups with two or more mechanical valves was lower than that of the groups with two or more bioprosthetic valves (0/10 versus 13/30; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431068 TI - Bilateral intralobar pulmonary sequestration with horseshoe lung. AB - We present an unusual case of a young woman with a several-month history of bronchopulmonary infection, symptomatic on the left side, who underwent complete studies showing bilateral pulmonary sequestration with suspected bridging tunnel. A bilateral resection was performed as a single procedure through a left thoracotomy. PMID- 8431069 TI - Giant hamartoma of the lung with a high production of carbohydrate antigen 19-9. AB - A rare case of a giant pulmonary hamartoma with a high production of carbohydrate antigen (CA) 19-9 is presented. A 43-year-old woman with complaints of cough, fever, and chest pain was diagnosed as having a posterior mediastinal tumor with pneumonia. The serum CA 19-9 level was high. A thoracotomy revealed an intrapulmonary solid mass with a histologic diagnosis of cartilaginous hamartoma with no evidence of malignancy. The CA 19-9 concentration in the mucus of the tumor was high, and postoperatively the serum CA 19-9 level returned to normal. The CA 19-9 could be immunohistochemically demonstrated on the surface of the tumor. PMID- 8431070 TI - Coronary revascularization in a patient with porcelain aorta and calcified great vessels. AB - Calcification of the aorta and great vessels in coronary artery bypass patients remains a challenging dilemma for the surgeon regarding bypass technique, choice of conduit, and available location of proximal anastomotic sites. Internal mammary artery flow may be inadequate, and the risk of systemic emboli from a diseased aorta is substantial. We report a case of a 69-year-old diabetic patient with a porcelain aorta extending into the aortic arch and great vessels who was revascularized using an altered anastomotic technique of right coronary artery endarterectomy for proximal anastomosis of vein grafts. Intraoperative echocardiographic evaluation of the aorta and arch was beneficial in determining extent of calcification. PMID- 8431071 TI - Malignant melanoma metastatic to the esophagus. AB - Malignant melanoma metastatic to the esophagus, as the only evidence of disease, is rare. We present the only known case treated at our institution and review 10 other cases reported in the world's literature. Of 11 patients (including ours) with melanoma metastasizing to the esophagus and no other known disease, no patient survived 1 year. With this dismal prognosis, the goal of therapy in these patients must be palliation of dysphagia. PMID- 8431072 TI - Surgical repair of aorto-right ventricular tunnel in an infant. AB - A rare case of aorta to right ventricle tunnel with associated pulmonary stenosis was corrected on cardiopulmonary bypass in a 3-month-old infant. Both the aortic and ventricular openings were closed with a patch. Although the repair was successful and the child was discharged from the hospital, septicemia developed and she died later. Early repair of this defect is recommended. PMID- 8431073 TI - Sequestration of the left coronary artery from the aorta. AB - A patient with the left coronary artery isolated from the ascending aorta is discussed. This is the seventh case described and the third diagnosed preoperatively. In contrast to other patients she had predominant aortic incompetence and was much older (52 years compared with the other patients, all younger than 25 years). She also had two angiograms demonstrating progressive isolation of the coronary artery with time. The patient was managed by aortic valve replacement. It is our belief that the condition is acquired and resulted from fusion of the free edge of the aortic valve leaflet to the supravalvar ridge secondary to an inflammatory process. PMID- 8431074 TI - Angiosarcoma of the heart causing cardiac rupture: a rare cause of hemopericardium. AB - Cardiac rupture as a complication of primary cardiac tumors has rarely been reported in the literature. The diagnosis is difficult to establish preoperatively, but echocardiography may provide the best assessment of cardiac damage. We found a loculated pericardial effusion on two-dimensional echocardiography, a finding that has been documented in two of the previous four case reports. A case of right atrial rupture is reported with review of other cases from the literature. PMID- 8431075 TI - Postcardiotomy LVAD support and transesophageal echocardiography in a child. AB - A case of postcardiotomy cardiogenic shock after repair of a congenital ventricular septal defect in a 5-year-old boy is reported. Mechanical circulatory support, instituted with a centrifugal left ventricular assist device, adequately supported the patient for 50 hours until recovery of native left ventricular function occurred. Transesophageal echocardiography proved to be useful in assessment of left ventricular function, allowing for timely institution and withdrawal of mechanical circulatory support. PMID- 8431076 TI - Warm heart surgery in patients with cold autoimmune disorders. AB - Continuous warm antegrade delivery of cardioplegia while maintaining systemic normothermia is a new method of performing coronary artery bypass grafting. It can be used to avoid the detrimental effects of hypothermia in patients with cold autoimmune disease. PMID- 8431077 TI - Use of a heat exchanger to prevent hypothermia during thoracic and thoracoabdominal aneurysm repairs. AB - Hypothermia is a common unplanned occurrence in many patients undergoing repair of thoracic and thoracoabdominal aneurysms. Many undesirable side effects of hypothermia have been documented, including decreased cardiac output, conduction abnormalities, and blood coagulopathies. We have developed a simple system that incorporates a Sci-Med Biotherm heat exchanger into our left heart bypass circuit. This provides us with the ability to actively rewarm the patient safely and efficiently. This study looks at 16 consecutive patients undergoing repair of thoracic or thoracoabdominal aneurysms. In the 9 patients in whom the heat exchanger was used, there were no adverse effects related to the heat exchanger. All patients had significantly higher temperatures at the conclusion of the procedure than the 7 patients in whom the heat exchanger was not used. PMID- 8431078 TI - Selective jugular cannulation of safer retrograde cerebral perfusion. AB - Hypothermic retrograde cerebral perfusion is a new technique for protecting the brain. Satisfactory cerebral protection should be possible even for periods of retrograde perfusion greater than 60 minutes. However, there are some concerns that functioning venous valves at the jugular-subclavian junction may impede retrograde flow to the brain and consequently cerebral protection may not be adequate. To overcome this obstacle, we have developed an easy and safe technique of selective jugular cannulation through the right atrium using a central venous catheter and a guidewire. We have employed this technique successfully in 15 patients who underwent operation on the aortic arch. PMID- 8431079 TI - Pericardioperitoneal window. AB - A technique to create a pericardial window is discussed. By creating a communication between the pericardial and peritoneal cavities, adequate drainage is obtained without the need for external draining systems. The technique is simple, easy to learn, and without serious complications. PMID- 8431080 TI - Preparation of autologous fibrin glue from pericardial blood. AB - To salvage patients' blood and improve hemostasis in cardiac operations, autologous fibrin glue was prepared in a new way by means of ethanol from pericardial blood. The yield from 44 mL of blood was 2.1 +/- 0.7 mL (mean +/- standard deviation) of fibrinogen concentrate with a concentration of 25.1 +/- 7.5 mg/mL; 2.7 mL of two-component glue was obtained after the addition of thrombin solution. The glue has the advantages of safety from transmission of viral diseases and from immunologic reactions. PMID- 8431081 TI - Sinus of Valsalva aneurysms and application of surgical science to their repair. PMID- 8431082 TI - Inflammatory response to cardiopulmonary bypass. AB - Cardiac operations with cardiopulmonary bypass cause a systemic inflammatory response, which can lead to organ injury and postoperative morbidity. Causative factors include surgical trauma, contact of blood with the extracorporeal circuit, and lung reperfusion injury on discontinuing bypass. Advances in immunological techniques have allowed measurement of both plasma and intracellular components of this multifaceted perioperative response. This includes activation of the complement, coagulation, fibrinolytic, and kallikrein cascades, activation of neutrophils with degranulation and protease enzyme release, oxygen radical production, and the synthesis of various cytokines from mononuclear cells (including tumor necrosis factor, interleukin-1, and interleukin-6). Advances in our understanding of the interactions between these markers of cellular and humoral responses to cardiopulmonary bypass will enable more effective intervention to reduce the deleterious effects and improve the outlook for patients undergoing cardiac operations beyond the 1990s. PMID- 8431083 TI - Carotid endarterectomy during aortic clamping. PMID- 8431084 TI - Prosthetic mitral valve replacement. PMID- 8431085 TI - Thoracoscopic thymoma resection. PMID- 8431086 TI - Resection of mycotic lung sequestra after invasive aspergillosis. PMID- 8431087 TI - Thoracic aortic dissection and atherosclerotic abdominal aortic aneurysm. PMID- 8431088 TI - Treatment of AIDS-related bronchopleural fistula by pleurectomy. PMID- 8431089 TI - Staged expanding pulmonary artery band. PMID- 8431090 TI - Transthoracic balloon pumps. PMID- 8431091 TI - Pericardioperitoneal shunt for persistent effusions. PMID- 8431092 TI - Embracing the future. PMID- 8431093 TI - John Stanley Coulter Lecture. The usefulness of qualitative methods in rehabilitation: issues of meaning, of context, and of change. PMID- 8431094 TI - Personal assistance: its effect on the long-term health of a rehabilitation hospital population. AB - After discharge from a rehabilitation hospital, persons with severe disabilities may not be able to maintain health effectively without adequate personal assistance with activities of daily living. Techniques of qualitative analysis were used to assess interview results based on the observations of 41 physicians, physical therapists, occupational therapists, social workers, and nurses in five rehabilitation hospitals. A positive relationship was found between the adequacy of personal assistance and the ability of individuals disabled primarily by stroke, spinal cord injury, or traumatic brain injury to maintain good physical and mental health. The most commonly cited health problem was skin breakdown, followed by urinary tract infections, pulmonary infections, and contractures. Inadequate personal assistance also led to extended hospital stays, threats to safety, poor nutrition, and poor personal hygiene. Reliance on family alone for assistance was considered inadequate, common adverse effects including burnout, family role changes, and economic strain. Persons with the best health combined assistance by relatives and unrelated persons. Recommended is the establishment of a comprehensive system capable of coordinating service delivery from home health agencies, independent living centers, and rehabilitation hospitals. PMID- 8431095 TI - Functional assessment scales: a study of persons after stroke. AB - The purpose of this study was to investigate disability in persons after stroke by using combinations of functional assessment item, subscale, domain, and full scale scores, to predict (1) the burden of care measured in minutes of assistance provided per day by another person in the home, and (2) the subject's level of satisfaction with life in general. The Functional Independence Measure (FIM) and the Sickness Impact Profile (SIP) each contributed to prediction of the subject's physical care needs. A change in total FIM score of one point (range, 61 to 126) was equivalent to an average of 2.19 minutes of help from another person per day and a change in one point in the SIP physical dysfunction (SIPPHYS) score (range, 4.0% to 57.4%) was equivalent to an average of 3.32 minutes. Along with the Brief Symptom Inventory and a measure of visual ability, the FIM contributed to predicting the patient's general satisfaction as well. The burden of care and subjective satisfaction with life in general are important standards by which functional assessment instruments may be compared to reflect, in pragmatic terms, the impact of disability on the lives of individuals and on the human and economic resources of the community. PMID- 8431096 TI - Predicting hours of care needed. AB - This study investigated whether the number of hours of care needed by a person with disability could be predicted by his or her score on the Functional Independence Measure (FIM) or the Edinburgh Rehabilitation Status Scale (ERSS). Seventy-five subjects (age range, 19 to 65), from a variety of residential services, with neurological disabilities, were visited by an experienced observer to estimate the number of hours of care per week required, from whatever source, for the subject to manage adequately. A second observer, blind to the observations of the first, assessed the subjects' FIM and ERSS scores by interview with the subjects and their carers. Wide ranges of scores on both scales suggested that subjects with many different dependency levels were surveyed, confirmed by "required care hours" varying between 0 and 168 per week (median 18). Pearson's correlation coefficients were 0.36 for ERSS (p < 0.002) and -0.39 for FIM (p < 0.001). Analysis of the scattergrams identified three aberrant cases. Investigation of these showed they each had a high level of dependency due to supervision rather than physical care; exclusion of these cases resulted in much stronger correlations for the remaining 72 cases (ERSS, 0.61; FIM, -0.76). Both ERSS and FIM correlate well with hours of care required, but their association with hours of supervision is poor. PMID- 8431097 TI - The relationship between constructional and meal preparation skills. AB - The purpose of this descriptive, correlational study was to explore the relationship between constructional abilities and meal preparation skills--a previously unstudied relationship. Fifty-four men with head injury, aged 18 to 52, in long-term rehabilitation programs, were given a battery of constructional, functional, and coordination tests: (1) the WAIS-R Block Design test; (2) a Parquetry Block test; (3) the Rabideau Kitchen Evaluation-Revised (RKE-R); and (4) two subtests of the Jebsen Hand Function Test. Results showed significant associations between constructional abilities and meal preparation skill. Pearson correlations were -0.51 (p = 0.0001) between WAIS-R Block Design test and RKE-R scores, and 0.50 (p = 0.0001) between Parquetry Block test and RKE-R scores. Partial correlations controlling for the effects of coordination also yielded significant correlations between WAIS-R Block Design test and RKE-R scores (r = 0.36, p = 0.05) and between Parquetry Block test and RKE-R scores (r = 0.39, p = 0.03). Constructional abilities, then, may contribute to meal preparation performance. PMID- 8431098 TI - Adaptive device use by older adults with mixed disabilities. AB - A key strategy in rehabilitation with the elderly is the selection and training in the use of adaptive devices to improve the ability to perform self-care and other activities of daily living. Two descriptive pilot studies were conducted to determine home use of equipment from the perspective of older adults with mixed disabilities and home care therapists. The first study examined home equipment use over a three-month period by 13 elderly patients discharged from a hospital rehabilitation unit. The second study surveyed 31 home therapists to evaluate their perceptions of device use by their elderly clients. The findings indicate that older adults and home care therapists share similar perspectives as to why devices are not frequently used. Home care therapists perceived that additional training in a person's home may increase safety, maximize functional performance, and reduce some caregiver responsibilities. The implications of these findings for service delivery are discussed. PMID- 8431099 TI - Effect of methylphenidate on brain injury-related anger. AB - Anger and temper outbursts can be serious clinical problems after brain injury. This study used a randomized, pretest, posttest, placebo control group, single blind design to evaluate the therapeutic usefulness of methylphenidate to control brain-injury-related anger. The 38 subjects in the study were young adult males who had sustained serious brain injuries and who were beyond the period of rapid, spontaneous recovery. The subjects were divided into two groups, one that received 30 mg of methylphenidate per day and the placebo control group. A comparison of the drug group with the placebo group before and at the end of the six-week treatment period on all the anger outcome measures analyzed simultaneously with multivariate analysis indicated a significant drug-by-time interaction effect, F(4.33) = 5.29, p = .002, demonstrating the therapeutic effect of methylphenidate on anger. The study found that drug responders could be predicted by pretreatment level of anger with a .09 probability of misclassification. Methylphenidate also significantly reduced impairment on all of the general psychopathology outcome measures (F[3.31] = 5.42, p < .01). The drug improved memory for those subjects in the treatment response group but did not result in changes on measures of attention, nor did it have an effect on a checklist of subjective side effects, suggesting that it has minimal or absent cognitive toxicity and is likely to be tolerated well by individuals with brain injuries. PMID- 8431100 TI - Motor performance in children after traumatic brain injury. AB - Traumatic brain injury can result in persistent impairments of motor performance that interfere with functional activities. This study compared the gross and fine motor performance of 14 traumatically brain-injured children (five to 15 years old, with loss of consciousness for at least 24 hours) to 14 normal children group matched for age and sex. All subjects had normal intelligence and no prior history of cognitive or motor delays. Subjects were assessed with the Bruininks Oseretsky Test of Motor Proficiency at least 16 months after injury. Results were compared using the Wilcoxon rank sum test. Highly significant differences were found between groups on the Gross Motor Composite. Although no significant differences were found on the Fine Motor Composite, a highly significant difference also was found on one of the fine motor sub-tests, Upper-Limb Speed and Dexterity. Subtest analysis revealed that when speed was a component of either fine or gross motor tasks, a pattern of significant differences was found. This is consistent with previous research in neuropsychology, which has demonstrated problems in speeded motor performance of children with brain injuries. These findings provide direction for further research, clinical assessment, and treatment of this at-risk population. PMID- 8431101 TI - The relationship of lower extremity strength and gait parameters in patients with post-polio syndrome. AB - Relationships between lower extremity strength and stride characteristics were studied in 24 patients with post-polio syndrome. Maximum isometric torques were measured in the ankle plantar flexors, hip and knee extensors, and hip abductors. Gait velocity, stride length, and cadence were recorded during free and fast walking. Step-wise regression analysis was performed to determine which muscle groups best predicted ambulatory function. Plantar flexion torque was the best predictor of velocity (r = .55 free walking and r = .76 fast) and cadence (r = .46 free and r = .58 fast). The combination of plantar flexion and hip abduction torques was the best predictor of fast stride length (r = .78). These findings emphasize the important role of the plantar flexor muscles in gait. Knee extension torque was the poorest predictor for each of the gait parameters. Several patients demonstrated gait deviations that minimized the penalty of quadriceps weakness. Without a contracture or an orthosis, however, no adequate substitution exists for weak plantar flexion. PMID- 8431102 TI - Airway secretion clearance by mechanical exsufflation for post-poliomyelitis ventilator-assisted individuals. AB - Pulmonary complications from impaired airway secretion clearance mechanisms are major causes of morbidity and mortality for post-poliomyelitis individuals. The purpose of this study was to review the long-term use of manually assisted coughing and mechanical insufflation-exsufflation (MI-E) by post-poliomyelitis ventilator-assisted individuals (PVAIs) and to compare the peak cough expiratory flows (PCEF) created during unassisted and assisted coughing. Twenty-four PVAIs who have used noninvasive methods of ventilatory support for an average of 27 years, relied on methods of manually assisted coughing and/or MI-E without complications during intercurrent respiratory tract infections (RTIs). Nine of the 24 individuals were studied for PCEF. They had a mean forced vital capacity (FVC) of 0.54 +/- 0.47L and a mean maximum insufflation capacity achieved by air stacking of ventilator insufflations and glossopharyngeal breathing of 1.7L. The PCEF were as follows: unassisted, 1.78 +/- 1.16L/sec; following a maximum assisted insufflation, 3.75 +/- 0.73L/sec; with manual assistance by abdominal compression following a maximum assisted insufflation, 4.64 +/- 1.42L/sec; and with MI-E, 6.97 +/- 0.89L/sec. We conclude that manually assisted coughing and MI E are effective and safe methods of airway secretion clearance for PVAIs with impaired expiratory muscle function who would otherwise be managed by endotracheal suctioning. Severely decreased maximum insufflation capacity but not vital capacity indicate need for a tracheostomy. PMID- 8431103 TI - Changes in pharyngeal dimensions effected by chin tuck. AB - This study measured the pharyngeal dimensions of 30 subjects when their heads were in an upright neutral position and in the chin-tucked position. Two videoprints of lateral radiographic views of the oral cavity and pharynx were made for each subject: one with the head in neutral position and one with the chin tucked. A 1-cm metal ruler was taped at midline on the front of each patient's neck to account for radiographic magnification of the image. Three angles and three distance measures were made on each videoprint. With the chin tucked, a posterior shift of anterior pharyngeal structures occurred, narrowing the laryngeal entrance and the distance from epiglottis to the pharyngeal wall and the laryngeal entrance, while widening the angle of the epiglottis to the anterior tracheal wall. This posterior shift with the chin tucked improves airway protection. Other clinical implications of these changes in pharyngeal dimensions are discussed. PMID- 8431104 TI - Failure of transcutaneous electrical nerve stimulation in the conventional and burst modes to alter digital skin temperature. AB - The purpose of this study was to determine if transcutaneous electrical nerve stimulation (TENS), when applied using stimulation settings that might be used in clinical practice, produces alterations in skin temperature. Stimulation in the conventional and burst modes was applied to the skin of the forearm overlying the median nerve in a healthy human subject. Skin temperature was measured at the index finger, little finger, and on the volar surface of the forearm in the stimulated limb. TENS applied for 20 minutes in the conventional mode at an intensity sufficient to produce a perceptible though not uncomfortable sensation and a slight muscle contraction of the forearm musculature failed to alter skin temperature at any of the three measurement sites. Stimulation using the same pulse characteristics delivered in the burst mode failed to alter skin temperature of the fingers but produced a significant increase in skin temperature at the forearm. The increase in skin temperature at the forearm persisted for four minutes following the cessation of stimulation after which skin temperature returned to prestimulation levels. We conclude that TENS, as applied in this study, does not influence skin temperature in the peripheral distribution of the nerve stimulated, and hypothesize that the rise in skin temperature at the forearm was a result of increased blood flow in the forearm muscles produced by the stimulation-induced contraction of those muscles. PMID- 8431105 TI - A radiological measure of shoulder subluxation in hemiplegia: its reliability and validity. AB - This study describes the reliability and validity of a new radiological method to measure shoulder subluxation that is based on taking a single x-ray of the affected shoulder in the plane of the scapula. A digitizer and a computer are used to quantify the measurements directly from the x-ray. One single radiological view of the shoulder taken in a standardized position provides four measures of subluxation including a measure of vertical subluxation, horizontal subluxation, a normalized distance sensitive to both vertical and horizontal subluxation, and an angular measure. A total of 72 volunteers with cerebrovascular accidents participated in the study. Thirty-six subjects had a clinical shoulder subluxation and 36 had no clinical subluxation. The construct validity analysis showed significant differences (p < .001) between the mean scores for subluxed and nonsubluxed groups on all four measures of subluxation. The concurrent validity of the x-ray measures in relation to external clinical measures (finger's breadth, measures in centimeters with calipers or a plexiglass jig) was moderate. Three measures were found to be reliable and valid whereas the fourth, a measure of horizontal subluxation has lower reliability. However, it does have clinical significance. The clinical and research implications of this study are presented. PMID- 8431106 TI - Instrumental straight-leg raising: results in healthy subjects. AB - The instrumental performance of Lasegue's test (instrumental straight-leg raising) provides information about the extensibility, elasticity, and electrical activity of hamstrings and back muscles and about pelvic rotation. Because relevant data on these variables are not known in literature, instrumental straight-leg raising was performed in healthy subjects. Using the toe-touch test, three groups of eight subjects were selected: a flexible group, able to touch the ground with their hands flat, a medium group, able to touch the ground with their finger tips, and a stiff group, not able to touch the ground at all. Measurements showed a considerable difference in the extensibility of the hamstrings between the groups with only a slight difference in the extensibility of the back muscles. They also showed clear differences in elasticity of the hamstrings and the back muscles in the subjects within the groups. Between the groups, however, muscle elasticity was not systematically different. Electromyogram activity was most often present in the subjects of the stiff group, predominantly in the hamstrings. It began only after the leg had been raised to a considerable extent, showed a gradual increase with leg raise, and never reached a high level. PMID- 8431107 TI - Cognitive remediation in traumatic brain injury: update and issues. AB - Cognitive Remediation (CR) is a relatively new treatment technique for alleviating residual cognitive deficits following traumatic brain injury. This is a promising yet still changing technique. The future of CR as a rational and systematic endeavor requires the incorporation of important new ideas that have been emerging in allied fields. For example, the emerging field of instructional psychology has contributed relevant concepts such as scaffolding, metacognition, and generalization. It is furthermore argued that the issues of awareness, self concept, and self-efficacy are vital to the process of CR intervention, and an integrative (holistic) approach to the remedial endeavor is thus indicated. PMID- 8431108 TI - Brainstem infarct with pharyngeal dysmotility and paralyzed vocal cord: management with a multidisciplinary approach. AB - An unusual case of right posterior brainstem infarction with isolated deficits of severe dysphagia and ataxia is presented. Neurological examination revealed dysfunction of the pharyngeal and laryngeal branches of cranial nerves IX, X, and a paralyzed right vocal cord. The patient was unable to swallow 1/4 teaspoon of applesauce. Modified barium swallow revealed extremely sluggish pharyngeal peristalsis and absent swallowing reflex. Percutaneous esophageal gastrostomy tube was inserted and an intensive dysphagia rehabilitation program was initiated. Pharyngeal-phase-oriented protocol was used. Results were significantly improved compensatory pharyngeal and laryngeal function with restoration of swallowing and no aspiration. This case illustrates successful management of dysphagia associated with brainstem infarction and the benefits of a coordinated multidisciplinary protocol. PMID- 8431109 TI - Attenuation of facial muscle spasticity with intramuscular phenol neurolysis. AB - Intramuscular phenol neurolysis is a well-known procedure used to decrease spasticity and improve function in patients who have failed to respond to more conservative forms of intervention. Traditionally, this approach has been limited to spasticity reduction in limb muscles, and its use in managing spasticity of the facial muscles has not been described in the literature. This case report describes a new and previously unreported application of intramuscular neurolysis for managing severe unrelenting facial muscle spasticity in a postanoxic encephalopathic patient. Prior to the procedure, hypertonicity in the orbicularis oris muscle was so profound that it limited speech and affected cosmetic, hygienic, and nutritional status. After intramuscular phenol neurolysis of the orbicularis oris muscle, the patient's level of functioning improved. PMID- 8431110 TI - An overhead harness and trolly system for balance and ambulation assessment and training. AB - Safe assessment of standing balance and gait is often jeopardized by the potential for falls, which may have major physical and legal consequences. This article describes the design and use of a system that enhances the safety of the patient and clinician during balance and gait assessment and training. The system consists of an overhead track and moveable trolly that allows the patient, while secured in a simple body harness, the freedom to ambulate, perform functional types of activities, and fall with minimal risk of injury. As a result, a single therapist can more readily assess balance and ambulation, as well as provide training for these skills. In addition, the therapist is free to observe the patient's movements from any position, without direct physical contact. Practically, the system described may allow ambulation training sooner after injury or surgery, permit training in weight-bearing or partial weight-bearing activities with or without assistive devices, and allow the clinician to focus on assessment and training, rather than on patient safety. PMID- 8431111 TI - Use of anticonvulsants in traumatic brain injury. PMID- 8431112 TI - Baboon livers and the human good. PMID- 8431113 TI - General surgery, the general surgical subspecialties, and prerequisite training. AB - Currently, several specialties (cardiothoracic, pediatric, and colorectal) require a full general surgery residency before specialty training. Plastic surgery has, in essence, a de facto requirement since most residents have had at least 5 years of general surgery training before initiation of a plastic surgery residency. Forces within both general surgery and plastic surgery will dictate that such a de facto requirement will not persist in the future. The pressures that compel plastic surgery to modify the traditional role of general surgery as preparatory training for requisite or specialty residency training can be extended by analogy to the other specialties as well. This article will hypothesize that the premises and the conclusions about the relationship between plastic surgery and general surgery apply equally well to the other specialties. If the traditional and historical role of full general surgery residency as prerequisite training for a specialty residency is discarded, careful thought must be given to any substitute system to graduate surgical education. In particular, attention must be directed to the three components of clinical skills to be acquired and to an expectation of operative or technical experience. PMID- 8431114 TI - Papers presented at the 12th Annual Meeting of the Surgical Infection Society. Los Angeles, California, April 9, 1992. PMID- 8431116 TI - Regulation of cytokine mRNA expression in lipopolysaccharide-stimulated human macrophages. AB - One of the responses of the human macrophage to lipopolysaccharide (LPS) is the production of a number of cytokines. The regulation of these cytokines is still not clearly understood. To study this regulation, mRNA levels of interleukin 1 alpha (IL-1 alpha), IL-1 beta, tumor necrosis factor alpha (TNF-alpha), IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-8/neutrophil chemotactic factor were determined in 10-day-old differentiated macrophages following stimulation with a low dose of LPS (0.001 to 10 ng/mL) with use of the polymerase chain reaction. Increased levels of mRNA for IL-8 were detectable after exposure to a very low dose of LPS (0.001 ng/mL) and levels of IL-1 beta and TNF-alpha were detectable only after stimulation with doses of 0.01 ng/mL. The mRNA for IL-8 was detected 30 minutes after the addition of LPS, while those for IL-1 beta and TNF-alpha were only measurable at 1 hour. The mRNAs for IL-1 alpha, IL-6, and GM-CSF were detectable only with a higher dose of lipopolysaccharide and only after a longer exposure time. In addition, the messages for IL-6 and GM-CSF were measurable for a short time, while those of IL 8 and of IL-1 beta were detectable for a longer time. The secretion of TNF-alpha and GM-CSF tightly followed gene activation, and that of IL-6 and IL-8 steadily increased even after the mRNA level of these cytokines returned to baseline. Secretion of IL-1 alpha and IL-1 beta was hardly detected, although their gene activation was obvious. These data indicate that cytokine mRNA levels following lipopolysaccharide stimulation are highly regulated. Individual cytokines show variable patterns of response. These responses are both dose and time dependent and are not necessarily associated with the secretion of protein. PMID- 8431115 TI - Elaboration of interleukin 1-receptor antagonist is not attenuated by glucocorticoids after endotoxemia. AB - The body's response to infection/inflammation is initiated by the elaboration of cytokines, such as tumor necrosis factor, interleukin 1-beta (IL-1-beta), IL-6, and IL-8. Cytokines, in turn, stimulate the pituitary-adrenal axis, and it has been suggested that the corticosteroids elaborated serve as negative feedback signals to diminish inflammatory events. To test this hypothesis, we administered hydrocortisone shortly before endotoxin administration to normal volunteers. Steroids greatly reduced the clinical response to endotoxin and attenuated the appearance of tumor necrosis factor, IL-6, and IL-8 in the circulation. In contrast, IL-1-receptor antagonist, a competitive antagonist of the IL-1 receptor, was unaffected by steroid administration. These data suggest that IL-1 receptor antagonist may act in synergism with corticosteroids to reduce inflammation. Elevation of concentrations of these two factors, corticosteroids and IL-1-receptor antagonist, in plasma appears to be the mechanism used by the body to overcome the effects of inflammatory cytokines. PMID- 8431117 TI - Blood transfusion increases the risk of infection after trauma. AB - To determine whether blood transfusion influences infection after trauma, we analyzed data on 5366 consecutive patients hospitalized for more than 2 days at eight hospitals over a 2-year period. The incidence of infection was significantly related to the mechanism of injury: penetrating injuries, 8.9%; blunt injuries, 12.9%; and low falls, 21.4%. Stepwise logistic regression analyses of infection using the variables age, sex, respiration rate in the emergency department, Glasgow Coma Scale in the emergency department, Injury Severity Score, shock (systolic blood pressure < 90 mm Hg on admission to the emergency department), and log of total amount of blood transfused during hospitalization showed that amount of blood received and Injury Severity Score were the only two variables that were significant predictors of infection across groups. Even when patients were stratified by Injury Severity Score, the infection rate increased significantly with increases in numbers of units of blood. Blood transfusion in the injured patients is an important independent statistical predictor of infection. Its contribution cannot be attributed to age, sex, or the underlying mechanism of severity of injury. PMID- 8431118 TI - Oral prostaglandin E2 prevents gut atrophy during intravenous feeding but not bacterial translocation. AB - The pathophysiologic changes in gut physiology that result in bacterial translocation during intravenous feeding are poorly defined, though believed to be related in part to intestinal atrophy, decreased mesenteric blood flow, and lack of intestinal secretions. This study investigated the hypothesis that pharmacologic preservation of intestinal structure and function by orally administered 16,16-dimethyl-prostaglandin E2 would prevent bacterial translocation in intravenously fed rats. Thirty-five rats were randomized to three groups: group 1 was fed rat chow ad libitum, group 2 received standard parenteral nutrition, and group 3 received parenteral nutrition plus oral 16,16 dimethyl-prostaglandin E2 (150 micrograms/kg twice a day). Rats were fed there respective diets for 5 days and killed. Mesenteric lymph nodes were procured for culture, and the intestine was assessed for weight, DNA, protein values, and histologic character. Results demonstrate that orally administered 16,16-dimethyl prostaglandin E2 potently attenuates the intestinal atrophy associated with parenteral feeding but does not prevent bacterial translocation. Intestinal barrier dysfunction and bacterial translocation during intravenous feeding is related to factors other than the development of gut atrophy. PMID- 8431119 TI - Pneumonia and stress ulceration in severely injured patients. A prospective evaluation of the effects of stress ulcer prophylaxis. AB - Stress ulcer prophylaxis is a routine aspect of the care of critically injured patients. Recent reports have suggested that patients undergoing prophylaxis with histamine antagonists are predisposed to nosocomial pneumonia, and that treatment with sucralfate can prevent this problem. An open, prospective randomized trial of three regimens was conducted with 278 evaluable patients. The patients were assigned to one of three group: the group receiving sucralfate, the group receiving a cimetidine hydrochloride bolus, and the group undergoing continuous infusion with cimetidine. Stress ulceration developed in 8% of patients in the sucralfate group, 13% of patients in the cimetidine bolus group, and 12% of patients in the cimetidine infusion group, while nosocomial pneumonia developed in 29% of patients in the sucralfate group, 32% of patients in the cimetidine bolus group, and 23% of patients in the cimetidine infusion group. Multivariate analysis of risk factors associated with pneumonia demonstrated independent significance for score on the Glasgow Coma Scale, Injury Severity Score, cord injury, shock, and head injury. Only spinal cord injury was associated with stress ulceration. We conclude that sucralfate and cimetidine are both effective for stress ulcer prophylaxis and that there is no association of cimetidine with nosocomial pneumonia. PMID- 8431120 TI - Surgical Infection Society intra-abdominal infection study. Prospective evaluation of management techniques and outcome. AB - This prospective, open, consecutive, nonrandomized trial examined management techniques and outcome in severe peritonitis. A total of 239 patients with surgical infection in the abdomen and an APACHE (acute physiology and chronic health evaluation) II score greater than 10 were studied. Seventy-seven patients (32%) died. Reoperation had a 42% mortality rate (35 of 83 patients died) compared with a 27% mortality rate (42 of 156 died) in patients who did not undergo reoperation. Forty-six patients underwent one reoperation; 15, two reoperations; 10, three reoperations; five, four reoperations; and seven, five reoperations, with mortality rates of 43%, 40%, 30%, 40%, and 57%, respectively. There was no significant difference in mortality between patients treated with a "closed-abdomen technique" (31% mortality) and those treated with variations of the "open-abdomen" technique (44% mortality). Logistic regression analysis showed that a high APACHE II score, low serum albumin level, and high New York Heart Association cardiac function status were significantly and independently associated with death. Low serum albumin level, youth, and high APACHE II score were significantly and independently associated with reoperation. PMID- 8431121 TI - Effects of extrahepatic obstructive jaundice on Kupffer cell clearance capacity. AB - Systemic endotoxemia consistently occurs in jaundiced patients undergoing surgery. Kupffer cell dysfunction is implicated in the development of endotoxemia and its postoperative complications. A novel in situ single-pass hepatic perfusion technique using a fluorescein isothiocyanate-labeled latex probe was developed for measuring Kupffer cell clearance capacity and was applied in an animal model of biliary obstruction. Control rats and rats jaundiced for 1, 2, 3, and 4 weeks' duration were studied. Kupffer cell clearance capacity, plasma bilirubin, endotoxin, and anticore glycolipid concentrations were measured. Maximal hyperbilirubinemia preceded reduced Kupffer cell clearance capacity. Rats jaundiced for greater than 2 weeks had a significantly decreased Kupffer cell clearance capacity but significantly higher endotoxin and anticore glycolipid concentrations. Anticore glycolipid concentrations correlated strongly with systemic endotoxemia and both were inversely correlated with duration of jaundice. Impairment of Kupffer cell clearance capacity may contribute to endotoxemia associated with cholestasis. PMID- 8431122 TI - Adventures in hemostasis. Desmopressin in cardiac surgery. AB - Desmopressin acetate (1-deamino-8-D-arginine vasopressin [DDAVP]) improves hemostasis in hemophilia A and von Willebrand's disease and in some platelet disorders. In complex cardiac operations, excluding simple coronary artery bypass graft procedures, we found that desmopressin reduced blood loss by 40% and the need for transfusion by 34%. Conflicting reports followed. Future trials should emphasize patients with excessive bleeding. A possible post-desmopressin prothrombotic state was studied after hip replacement surgery. The incidence of deep vein thrombosis associated with warfarin sodium therapy was the same as that associated with desmopressin plus warfarin therapy. No desmopressin-induced thrombotic tendency was detected. A trend toward reduced blood loss with desmopressin was not significant. During cardiac catheterization, the plasma von Willebrand factor level was correlated with hemodynamic variables, including pulmonary vascular resistance, pulmonary arterial pressure, and (inversely) with cardiac index. von Willebrand factor concentration was highest in mitral stenosis. The relationship of these factors to the response to desmopressin remains to be defined. PMID- 8431123 TI - Postoperative intra-abdominal sepsis requiring reoperation. Value of a predictive index. AB - In this study we analyze the results of the use of a predictive index to decide whether to perform abdominal reoperation in the event of septic complications. During a 5-year period, a population of 542 critically ill patients received major abdominal surgery. Patients were divided into two groups: (1) the control group, for which the decision to reoperate was made routinely, based on clinical consensus of the medical team; and (2) the Abdominal Reoperation Predictive Index group, for which the decision to reoperate was made with the help of a mathematical index involving eight mainly clinical variables. The use of Abdominal Reoperation Predictive Index enabled mortality among patients undergoing reoperation to be lowered, the time elapsing between the first operation and relaparotomy to be reduced, and the length of stay in the intensive care unit to be shortened. We conclude that the systematic application of an index, without disregarding clinical judgment, allows the quality of attention to be improved, cost to be lowered, and the level of conflicts generated by the difficult decision to perform reoperation to be curtailed. PMID- 8431124 TI - Single-dose ceftriaxone, ornidazole, and povidone-iodine enema in elective left colectomy. A randomized multicenter controlled trial. The French Association for Surgical Research. AB - Patients undergoing elective left colectomy for colonic carcinoma or diverticulosis (n = 341) were randomly assigned to three groups. Patients in groups 1 (102 patients) and 2 (122 patients) had two 5% povidone-iodine enemas whereas those in group 3 (117 patients) had saline enemas. Groups 1 and 3 received 24-hour intravenous cefotaxime sodium and metronidazole hydrochloride. Group 2 received single injections of ceftriaxone sodium (1 g) and ornidazole (1 g). Senna concentrate was administered the evening before surgery. There was no statistically significant difference found between groups 1 and 2 concerning the number of infected patients (eight vs 11), anastomotic leakages (four vs four), extra-abdominal complications (32 vs 29), or infection-related deaths (one vs zero). Despite poorer tolerance, povidone-iodine enema was more effective than saline enemas, as there were less infected patients in group 1 (8%) or groups 1 + 2 (8.5%) than in group 3 (13%). Single-dose ceftriaxone-ornidazole combined with povidone-iodine enemas is effective against infective complications in elective left colonic surgery for carcinoma or diverticular disease. Single-dose antibiotic prophylaxis reduces costs and work for the nursing staff. PMID- 8431125 TI - Laser vs electrosurgery in laparoscopic cholecystectomy. A prospective randomized trial. AB - While much of the clamor over the optimal instrument for dissection of the gallbladder from the liver bed has died, there remain no prospective comparative data concerning this issue. We undertook a prospective randomized trial comparing the contact neodymium:YAG laser with monopolar electrosurgical dissection in 100 patients undergoing laparoscopic cholecystectomy. Electrosurgical dissection was performed with an "L" hook and spatula electrodes at 25 W coagulation current. Neodymium:YAG laser dissection was performed with a 1200-microns contact tip at 15 W continuous beam. Mean (+/- SD) gallbladder dissection time was 19.2 +/- 8.5 minutes with electrosurgery compared with 23.6 +/- 9.6 minutes with the laser. Estimated blood loss was significantly less in the electrosurgery-treated group. In six instances, laser malfunction or fiber fragmentation necessitated completing the dissection with electrosurgery. We conclude that electrosurgery appears to have significant advantages for dissection of the gallbladder during laparoscopic cholecystectomy. PMID- 8431126 TI - Endoscopic procedures of the upper-thoracic sympathetic chain. A review. AB - The upsurge of endoscopic surgical procedures now includes procedures of the thoracic sympathetic chain. The number of articles on this issue is rapidly increasing. This article reviews the indications for as well as the technique, complications, side effects, and results of endoscopic upper-thoracic sympathetic ablation. Since 1977, nearly 900 cases have been described in the literature. The main indication is usually hyperhidrosis. The described techniques vary in detail, but the common denominators are simplicity, expedience, minimal surgical trauma, few complications, and low cost compared with standard methods of open surgery. The results are excellent, durable, and stand well compared with results of previous open techniques. Due to the overwhelming advantages of endoscopic methods, we can foresee an increasing adoption of these techniques and a subsequent relegation of the various open surgical procedures of the upper thoracic sympathetic chain. PMID- 8431127 TI - Effect of combined prednisolone, epidural analgesia, and indomethacin on the systemic response after colonic surgery. PMID- 8431128 TI - Psychopathology in metachromatic leukodystrophy. PMID- 8431129 TI - Brain death. PMID- 8431130 TI - Safety of intravenous immunoglobulin. PMID- 8431131 TI - Acute renal failure resulting from intravenous immunoglobulin therapy. AB - In idiopathic thrombocytopenic purpura, a known immune-mediated disorder, intravenous IgG is the treatment of choice. Success and the lack of side effects of intravenous IgG in the treatment of idiopathic thrombocytopenic purpura have encouraged consideration of its use in the treatment of neurologic disorders of presumed autoimmune pathogenesis. In this report, we describe two patients who developed acute renal failure following intravenous IgG treatment. The first patient had chronic inflammatory demyelinating polyneuropathy and was treated with intravenous IgG instead of prednisone because of preexisting diabetes. The second patient had idiopathic thrombocytopenic purpura and received intravenous IgG treatment as part of standard care. The patient with idiopathic thrombocytopenic purpura had unrelated bilateral high-grade renal artery stenosis. Both patients had a creatinine level of 140 mumol/L (1.6 mg/dL) prior to treatment. Renal biopsies performed during acute renal failure in each patient demonstrated marked swelling and vacuolization of the proximal tubular epithelial cytoplasm typical of high-solute-load-induced damage (similar to that associated with the use of mannitol). This report draws attention to the importance of screening for impaired renal function before intravenous IgG therapy is initiated. The patients we describe received standard doses of intravenous IgG at the recommended infusion rate yet developed oliguric renal failure. Awareness of serious side effects and recognition of predisposing factors provide means of avoiding known life-threatening complications of intravenous IgG therapy. PMID- 8431132 TI - A clinicopathologic study of 100 cases of Parkinson's disease. AB - The clinical details of 100 cases of histologically confirmed Parkinson's disease were examined and correlated with pathologic findings. Age at disease onset (mean, 62.4 years), disease duration (mean, 13.1 years), and age at death (mean, 75.5 years) were similar to those in previous smaller series. Asymmetric, tremulous onset was most common, although 23% of patients had no rest tremor. Motor fluctuations and dyskinesias occurred in 60% of levodopa-treated patients. All patients had clinical parkinsonism; however, 12 had atypical clinical features of Parkinson's disease, including severe early dementia, fluctuating confusional states, no response to levodopa, and early marked autonomic disturbance. Neuropathologic examination found coexistent Alzheimer-type change in 17 cases and striatal abnormality--mainly vascular--in 34 cases. Cortical Lewy bodies were present in all cases, but only four satisfied proposed criteria for diffuse Lewy body disease. Dementia occurred in 44% of cases; 29% had Alzheimer's disease, 10% had numerous cortical Lewy bodies, and 6% had a possible vascular cause; in 55% no definite pathologic cause was found. Nigral cell loss correlated with disease duration and severity. Although the general pattern of disease conformed to traditional descriptions, the findings broaden the present clinical and pathologic spectrum of Parkinson's disease. PMID- 8431133 TI - Parkinson's disease mortality in Italy, 1951 through 1987. Analysis of an increasing trend. AB - Parkinson's disease mortality was analyzed in Italy for the period from 1951 through 1987. The adjusted mortality was 4.27 and 2.77/100,000 population, respectively, for men and women. Adjusted rates increased in both sexes (63% increase in men and 80% in women in 1983 through 1987 vs 1951 through 1952). Age specific mortality increased in subjects aged over 75 years and decreased in those under 64 years. The analysis by birth cohorts demonstrated higher rates in the cohorts born between 1890 and 1910 than in those born before and after that period. Even if these changes in Parkinson's disease mortality might reflect better case ascertainment and the increase of life expectancy of patients with Parkinson's disease, there is some evidence that the temporal variation is associated with the changing experiences of different birth cohorts. PMID- 8431134 TI - Anterior inferior cerebellar artery territory infarcts. Mechanisms and clinical features. AB - Arterial lesions, mechanisms, territory, and clinical features of anterior inferior cerebellar artery (AICA) territory infarcts are only based on necropsy cases. To our knowledge, no large clinical series has been reported. We selected nine consecutive patients with AICA territory infarction confirmed by magnetic resonance imaging and angiography. Atherosclerosis was the only cause and all patients were hypertensive. Patients with pure AICA territory infarcts (n = 4) were diabetic and likely had basilar branch occlusion due to basilar artery plaques that extended into the AICA or microatheroma that blocked the AICA origin. These patients had no or had only recently had (1 day) prodromata. Patients with AICA plus infarct (n = 5) had basilar artery occlusion at the AICA and reconstitution of the distal basilar artery by collaterals through hemispheric anastomoses from the posterior inferior cerebellar arteries and posterior communicating arteries. All these patients except one had prodromata. In seven of nine patients, cranial nerve involvement indicated a lateral pontine lesion in the territory supplied by the AICA. Only two patients had the complete AICA syndrome, and none of the patients had isolated vertigo. The outcome was good in seven of nine patients. Isolated unilateral AICA infarcts should be regarded as most likely due to small artery atherosclerotic disease in diabetic patients. More widespread infarctions that include that AICA territory are due to basilar artery occlusive disease. PMID- 8431135 TI - Risk factors for cerebrovascular disease as correlates of cognitive function in a stroke-free cohort. AB - We investigated the relationship between risk factors for cerebrovascular disease and cognitive function in 249 stroke-free community volunteers (age, 70.8 +/- 6.7 years; education, 12.3 +/- 4.6 years) who were given tests of memory, language, visuospatial, abstract reasoning, and attentional skills. Using logistic regression analyses, we examined hypertension, diabetes mellitus, myocardial infarction, angina, hypercholesterolemia, and cigarette smoking as potential correlates of performance within these cognitive domains. Controlling for demographic factors within the logistic models, diabetes mellitus was a significant independent correlate of abstract reasoning deficits (odds ratio, 10.9; 95% confidence interval, 2.2 to 54.9) and visuospatial dysfunction (odds ratio, 3.5; confidence interval, 1.2 to 10.7), while hypercholesterolemia was a significant independent correlate of memory dysfunction (odds ratio, 3.0; confidence interval, 1.4 to 6.6). Prolonged exposure to vascular risk factors such as diabetes mellitus and hypercholesterolemia may lead to atherosclerotic disease, possibly resulting in "silent" infarctions or impaired cerebral blood flow and a decline in cognitive functioning. PMID- 8431136 TI - Magnetic resonance imaging with gadolinium contrast agent in small deep (lacunar) cerebral infarcts. AB - OBJECTIVE: To assess gadolinium-diethylenetriamine-pentaacetic acid (Gd-DTPA) contrast-enhanced magnetic resonance (MR) imaging as an index of recent symptomatic small deep cerebral infarcts (SDCIs). DESIGN: Prospective case series. SETTINGS: Primary-care center. PATIENTS: Thirty-one consecutive patients presenting with the clinical diagnosis of SDCI in the territory of the perforators of the internal carotid artery or the vertebrobasilar system and confirmed by MR imaging. INTERVENTION: Rapid intravenous infusion of Gd-DTPA 5 to 10 minutes prior to acquisition of T1-weighted images. MAIN OUTCOME MEASURES: Precise clinicotopographic correlation on MR scans. RESULTS: Non-contrast enhanced MR imaging allowed precise clinicotopographic correlation in five (38%) of 13 patients with SDCI symptoms in the internal carotid artery territory. After Gd-DTPA administration, precise clinicotopographic correlation improved in 11 (85%) of 13 patients. In five patients, precise correlation was possible only after Gd-DTPA enhancement. Nonenhanced MR imaging allowed precise clinicotopographic correlation in 15 (83%) of 18 patients with SDCI symptoms in the vertebrobasilar territory. After Gd-DTPA administration, we could establish precise clinicotopographic correlation in all patients with SDCIs in the vertebrobasilar territory. In three patients, precise correlation was possible only after Gd-DTPA contrast enhancement. In seven (23%) of 31 patients, Gd-DTPA failed to enhance symptomatic lesion: in five patients MR scans were performed early (less than 7 days) and in two patients later in the course (greater than 7 days). CONCLUSIONS: Although Gd-DTPA administration is unlikely to improve the sensitivity of MR images in visualizing SDCIs, it significantly improves the rate of precise clinicoanatomic correlation. All enhancing lesions showed precise clinicotopographic correlation. Enhancement may be absent in the acute phase (less than 7 days). PMID- 8431137 TI - Neuroradiological manifestations of focal polymorphic delta activity in children. AB - To examine the neuroradiological and clinical correlations of focal continuous polymorphic delta activity (PDA) in children, we reviewed the records of patients with continuous PDA that was either focal or lateralized to one hemisphere. Of 2571 electroencephalograms (EEGs) performed between July 1, 1988, and December 31, 1990, a total of 125 records from 87 patients revealed continuous PDA. Eighty of these patients had neuroimaging performed either by computed tomographic scan (n = 59) or by magnetic resonance imaging (n = 38) within 8 weeks of the EEG. Twenty-two patients (28%) showed no abnormalities on neuroimaging, 16 patients (20%) showed diffuse abnormalities, and 42 patients (52%) showed focal abnormalities that correlated with the EEG findings. Most (18 of 22) patients with no neuroradiological abnormalities presented to the hospital with seizures from various causes. The presence of focal spikes or additional focal EEG abnormalities did not differ significantly among the three imaging groups. Generalized EEG abnormalities and multifocal spikes were significantly more common among the patients who had generalized abnormalities on neuroimaging. Focal continuous PDA without correlated changes on neuroimaging occurred in 48% of patients, which is much higher than what has been reported in adults. PMID- 8431138 TI - Cerebral morphologic distinctions between Williams and Down syndromes. AB - Neurobehavioral studies of Williams syndrome (WS) and Down syndrome (DS) have revealed distinct profiles of cognitive strengths and weaknesses. In a previous report, we described several gross brain morphologic distinctions on magnetic resonance images between these two disorders. While the observed cerebral hypoplasia was of equal degree in the two groups, cerebellar size was entirely normal in the subjects with WS but dramatically reduced in subjects with DS. In WS, paleocerebellar vermal lobules subtended a smaller area on midsagittal sections, but neocerebellar lobules were actually larger. These results suggested important distinctions between WS and DS in terms of the action and anatomic targets of factors that alter brain development in these syndromes. The present study extends the earlier findings by focusing in detail on the morphologic features of the cerebral hemispheres, particularly cerebral gray matter. The results suggest that some frontal and temporal limbic structures are relatively preserved in WS, while some basal ganglia and diencephalic structures are relatively preserved in DS. PMID- 8431139 TI - Profiles of language impairment in primary progressive aphasia. AB - OBJECTIVE: The profile of language impairment in patients with primary progressive aphasia in comparison with the language impairment in patients with Alzheimer's disease and after stroke. DESIGN: The Western Aphasia Battery and the Mattis Dementia Rating Scale evaluated the language and cognitive impairment. Follow-up studies were done 1 to 5 years after the initial testing in seven of 10 patients with primary progressive aphasia, and a postmortem examination of the brain was done in two patients. SETTING: All 10 patients with primary progressive aphasia were previously healthy, community-dwelling persons when first tested. PATIENTS AND OTHER PARTICIPANTS: All patients with primary progressive aphasia reported at least a 2-year history of slowly progressive aphasia without other signs of global dementia. The initial Western Aphasia Battery results of the 10 patients with primary progressive aphasia were compared with those of a sample of 10 patients with probable Alzheimer's disease and with those of a sample of 10 patients with aphasia due to a left hemispheric stroke. Both reference samples were matched for age and sex; the sample with stroke-caused aphasia was additionally matched for the aphasia type. RESULTS: Expressive language disability with reduced speech fluency and anomia but preserved language comprehension and nonverbal cognition were typical features in early stages of primary progressive aphasia. Spontaneous speech was significantly more impaired in patients with primary progressive aphasia in comparison with those with aphasia after left hemisphere stroke and with language impairment in patients with Alzheimer's disease. Follow-up examinations revealed continuous, often rapid deterioration of language impairment. The neuropathological examination showed Alzheimer's disease in one patient and Pick's disease in the other. CONCLUSION: The profile of aphasia suggests that primary progressive aphasia tends to affect anterior parts of the language-dominant cortex first. PMID- 8431140 TI - Unilateral reduction of head pain and facial vasodilatation after gasserian ganglion lesion. AB - The features of histamine-induced headache and its associated vascular responses were studied in 52 patients with different surgical lesions of the gasserian ganglion and in 12 control subjects. Certain features of headache (eg, intensity, type, and duration) were similar in patients and control subjects. However, the pain was absent on the side of the trigeminal lesion in 26 (50%) of the patients. This unilateral absence of pain was not related to the hypoesthesia that was caused by the operation, and it was associated with a decrease in vascular responses (histamine-induced facial flushing and increase in temperature) on the side operated on. These abnormalities were more prevalent in patients who had undergone thermocoagulation and presented with more severe damage of the trigeminal ganglion than in those who were subjected to trigeminal compression or glycerolization. The trigemino-vascular system seems to control headache of a vascular type and associated craniofacial vasodilatation in human subjects. PMID- 8431141 TI - Clinical, neuroimaging, and environmental risk differences in monozygotic female twins appearing discordant for dementia of the Alzheimer type. AB - OBJECTIVE: The study of monozygotic twins can elucidate possible environmental causes for a disease in genetically identical subjects. To this end, we studied a pair of monozygotic female twins appearing discordant for dementia of the Alzheimer type (DAT). DESIGN: Clinical and neuroimaging findings were compared in terms of potential environmental risk factors. SETTING: University referral center. PARTICIPANTS: An 81-year-old female monozygotic twin pair. OUTCOME MEASURES: Clinical assessments, standardized rating scales, and brain imaging studies, including magnetic resonance imaging, positron emission tomography, and electroencephalography, were performed. Neuropsychological tests were performed initially and after 1 year. RESULTS: Although DAT was confirmed clinically in only one twin, neuropsychological and brain imaging studies suggested that the unaffected twin may be developing the prodrome of DAT. The twins' varied life histories suggest that environmental risk factors may contribute to apparent discordance for DAT and possible delay in disease onset for the currently nondemented twin. CONCLUSIONS: These results suggest that both genetic and nongenetic factors influence disease onset and expression. Moreover, review of previous reports of monozygotic twin pairs concordant or discordant for Alzheimer's disease, with adequate family history data, suggest a pattern indicating interactions among age at dementia onset, sex, and familiarity. Such patterns point to hypotheses regarding neurobiologically meaningful Alzheimer's disease subgroups. PMID- 8431142 TI - Local anesthesia for vitreoretinal surgery. PMID- 8431143 TI - Neuroimaging of the optic nerve after fenestration for management of pseudotumor cerebri. PMID- 8431144 TI - Needle-assisted scleral fixation suture technique for relocating posteriorly dislocated IOLs. PMID- 8431145 TI - Brow-supported spectacle frames for nasal bridge reconstruction and other deformities. PMID- 8431146 TI - Ciliary body adenoma in a 10-year-old girl who had a rhabdomyosarcoma. PMID- 8431147 TI - Refuge blindness. PMID- 8431148 TI - Detection of varicella-zoster virus DNA in disciform keratitis using polymerase chain reaction. PMID- 8431149 TI - Symblepharon associated with cyanoacrylate tissue adhesive. PMID- 8431150 TI - Long-term retention of chromic occlusion suture in glaucoma seton tubes. PMID- 8431151 TI - Pellucid marginal degeneration treated by lamellar and penetrating keratoplasty. PMID- 8431152 TI - Medicare trust funds on shaky ground. PMID- 8431153 TI - Does wavelength matter when photocoagulating eyes with macular degeneration or diabetic retinopathy? PMID- 8431154 TI - Unsuspected glove perforation during ophthalmic surgery. AB - OBJECTIVES: To determine the rate of perforation of surgical gloves after ophthalmic surgery and to identify factors that contribute to the development of perforations. DESIGN: Case-control study of used and unused surgical gloves collected during a 7-month period. SETTING: The ophthalmology surgical suites of a major teaching hospital. MAIN OUTCOME MEASURES: Development of glove perforations as measured by five different techniques. RESULTS: We tested 103 pairs of latex surgical gloves before use and 454 pairs of gloves after use. Of five techniques used to test for pinholes, air inflation with water submersion and compression was found to be the most sensitive, yielding a 6.80% prevalence in control glove pairs and a 21.81% prevalence in study glove pairs (P = .0005). When examined by subspecialty area, the lowest perforation rate (11.39%; P = .00009) occurred in cataract and intraocular lens surgery and the highest rate (41.67%; P = .003) occurred in oculoplastic surgery. Factors that correlated significantly with the development of perforations as determined by multiple logistic regression analysis included pediatric ophthalmology and strabismus surgeries, oculoplastic surgeries, level of training of the surgeon, duration of operation, and larger glove size. The thumb and index fingers of the nondominant hand contained the largest numbers of pinholes. CONCLUSIONS: The rate of surgical glove perforation after ophthalmic surgery is relatively high. Recommendations for reducing the rate of glove perforation are discussed. PMID- 8431155 TI - Autosomal dominant vitreoretinochoroidopathy. Report of the third family. AB - A family composed of 13 affected members in five generations (10 patients from four generations examined) had vitreal and ophthalmoscopic findings characteristic of autosomal dominant vitreoretinochoroidopathy, as described in two previous kindreds. Visual acuity was 20/25 or better in all but one patient. All affected individuals had vitreous liquefaction with or without peripheral vitreal condensations. Peripheral pigmentary changes and choroidal atrophy were characteristic. Six patients developed cataracts in their early 40s that required extraction. One patient had glaucoma, one developed a retinal detachment, and one had a spontaneous vitreous hemorrhage. Autosomal dominant vitreoretinochoroidopathy is a well-defined condition featuring presenile cataracts, vitreal degeneration, characteristic ophthalmoscopic findings, and good visual prognosis. PMID- 8431156 TI - The initial clinical characteristics of Graves' orbitopathy vary with age and sex. AB - A better understanding of the clinical nature of Graves' orbitopathy will aid in the treatment of the disease as well as help to form a basis for clinical and pathophysiologic investigations. We studied the clinical data of 557 consecutive patients who were referred for treatment of Graves' orbitopathy. Clinical indexes were calculated based on ophthalmologic variables measured, grouped in the following categories: soft tissue, proptosis, muscle limitation, increase in intraocular pressure on upgaze, corneal staining, and visual acuity. The mean age at onset of orbital disease was 43.9 years for men and 44.4 years for women, an average of 2.5 years from the onset of thyroid disease. The male-female ratio was 0.29 in all age groups. Women were more likely to present with orbitopathy and hypothyroidism than were men (20% vs 11%) and less likely to be euthyroid (16% vs 34%, P < .01). Patients older than 50 years, compared with their younger counterparts, more often had symptoms of impaired ocular motility (32% vs 12%), signs of soft-tissue involvement (77.5% vs 68.6%), asymmetric soft-tissue involvement (15.6% vs 7.8%), more limited upward duction (22.2 degrees vs 29.4 degrees), and more impaired LogMAR visual acuity (0.092 vs 0.047, P < .01). Men had more limited upward duction than women (24.6 degrees vs 27.1 degrees) and greater increases in intraocular pressure on upgaze (7.80 mm Hg vs 5.78 mm Hg, P < .001). These data show thyroid orbitopathy to be a disease most common in younger women, but more severe, by most indexes, in men and patients older than 50 years. These groups of patients are also more likely to have asymmetric or euthyroid disease. PMID- 8431157 TI - Evaluation of driving performance in patients with juvenile macular dystrophies. AB - The driving performance of 20 subjects with central vision impairment due to either Stargardt disease or cone-rod dystrophy (visual acuity, 20/40 to 20/70) was compared with that of 29 control subjects with normal vision who had similar driving histories. Driving performance was defined by accident involvement based on self-report and state records and by an evaluation of performance on an interactive driving simulator. The proportion of individuals involved in accidents in the central vision loss group was comparable to that of the control group. For 13 of the 20 subjects with central vision loss who did not restrict their driving to daylight hours, there was a greater likelihood of involvement in nighttime accidents than in the control group. Visual function measures and simulator indexes did not predict accident involvement for the central visual loss group, although these subjects showed longer braking response times and a greater number of lane boundary crossings than the control group. These findings are in contrast to our previously published report of subjects with retinitis pigmentosa, who were more likely to have been involved in both daytime and nighttime accidents than a control group and for whom visual field extent was significantly related to accident involvement. PMID- 8431158 TI - Do tinted lenses improve the reading performance of dyslexic children? A cohort study. AB - The use of tinted lenses as a method to improve reading skills in children with dyslexia has been a controversial issue in recent years. The purpose of the present study was to determine if tinted lenses cause a measurable improvement in the reading performance of dyslexic children. Twenty-four children aged 8 to 12 years participated in the study. Dyslexia was diagnosed in all children by psychological evaluation, and these children underwent an ophthalmic evaluation for inclusion into the study. Participants were graded for speed and accuracy as they read through spectacle frames that contained red-, blue-, yellow-, and green tinted lenses, a neutral-density lens, and empty frames. All lenses for each subject were of the same density level, with subjects alternately distributed to one of two densities tested (0.12 or 0.30 log units). Each child was asked to select the lens condition that subjectively improved reading ability at the conclusion of testing. One-way analysis of variance of reading performance showed neither improvement nor deterioration attributable to lens color or density when applied to error rates (F = 1.73, P = .14 for a density of 0.12; F = 0.28, P = .92 for a density of 0.30) or to reading rates (F = 0.98, P = .44 for a density of 0.12; F = 0.81, P = .55 for a density of 0.30). In addition, the lens condition that was subjectively preferred by each child did not correlate with actual reading performance (chi 2 = 3.83, not significant; 11.07 needed for significance at P = .05). PMID- 8431159 TI - Paralysis of downgaze in two patients with clinical-radiologic correlation. AB - Selective downgaze paralysis was correlated with discrete bilateral lesions at the mesencephalic-diencephalic junction in a 9-year-old girl following severe pneumococcal meningitis, and in a 64-year-old man who suffered an embolic infarction. Magnetic resonance imaging demonstrated bilateral lesions in the region of the rostral interstitial nucleus of the medial longitudinal fasciculus. Clinical-radiologic correlation allowed identification of the likely vascular cause in both patients. PMID- 8431160 TI - Acne rosacea with keratitis in childhood. AB - We present three cases of acne rosacea keratitis that developed in childhood. All three children were prepubescent and demonstrated characteristic dermatologic findings involving the nose, cheeks, and/or chin. The patients had complained of ocular irritation for at least 6 months, and in one case symptoms were reported by the family to have occurred intermittently since age 4 years. All three children showed evidence of meibomian gland inflammation; two patients demonstrated bilateral keratitis, the third had only unilateral involvement. In each case, oral tetracycline hydrochloride or doxycycline hyclate was necessary to relieve symptoms. Rosacea keratitis should be considered in the differential diagnosis of chronic keratoconjunctivitis during childhood. PMID- 8431161 TI - Baseline visual field profile of optic neuritis. The experience of the optic neuritis treatment trial. Optic Neuritis Study Group. AB - The purpose of the present study was to determine the baseline visual field characteristics in 448 patients with acute optic neuritis who were entered into the Optic Neuritis Treatment Trial. The severity and pattern of visual field loss in both the affected and fellow eyes were classified. For affected eyes, diffuse visual field loss was present in 48.2% of eyes, central or centrocecal scotoma was present in 8.3% of eyes, altitudinal or other nerve-fiber bundle-type defects were present in 20.1% of eyes, and a variety of other defects were present in 23.4% of eyes. Visual field involvement was present in the fellow eye at baseline in 308 (68.8%) of the 448 patients. Evidence of a chiasmal or retrochiasmal visual field defect was present in 2.9% of the patients. Since a wide variety of visual field defects can occur with an acute attack of optic neuritis, the pattern of visual field loss is of limited utility in distinguishing optic neuritis from ischemic optic neuropathy and other optic nerve disorders. Asymptomatic visual field defects in the fellow eye are common. PMID- 8431162 TI - Congenital zonular cataract. Clinicopathologic correlation with electron microscopy and review of the literature. AB - A whole subluxated lens with a congenital zonular cataract was obtained after intracapsular extraction from an 83-year-old patient for histopathologic examination. The first electron microscopic description of a congenital zonular cataract revealed the presence of many globules ranging in diameter from 0.1 to 2.5 microns, occasionally accompanied by enlarged intercellular spaces and a few multilamellar bodies. Most of the globules were arranged concentrically around the nucleus like a shell, and only a few globules were concentrated in nodular aggregates in the nucleus. Ultrastructural indications of the relationship between globules and lens fiber membranes have substantiated the idea of the transformation from normal lens fibers into cataractous fibers by primary breakdown of the lens fiber membranes and secondary degeneration or liquefaction of the fiber contents. PMID- 8431163 TI - Peripseudophakic membrane. Pathologic features. AB - A 70-yr-old woman underwent anterior segment reconstruction with repeated penetrating keratoplasty for visual rehabilitation. On removal of the failed keratoplasty button, the posterior chamber intraocular lens was found to be encased in a dense fibrous membrane that almost totally obliterated the anterior and posterior chambers of the eye. Anterior segment reconstruction included excision of the fibrous membrane, removal of the intraocular lens, iridoplasty, gonioplasty, anterior vitrectomy, and repeated penetrating keratoplasty. Recognition of fibrous tissue that extended through each of the four positioning holes of the optic of the lens implant and its transection was essential in avoiding complications during removal of the intraocular lens. Histopathologic and ultrastructural examination of the excised membrane revealed areas of metaplastic lens epithelium and fibrous scar tissue. This study, using immunofluorescence, is the first, to our knowledge, to characterize the specific collagenous components of a peripseudophakic membrane. PMID- 8431164 TI - Influence of haptic materials on the adherence of staphylococci to intraocular lenses. AB - A recent case-control study indicated that the insertion of an intraocular lens with polypropylene (Prolene) haptic materials was a significant risk factor for postoperative endophthalmitis (odds ratio = 4.5, P < .01). In the present study, we used quantitative techniques to evaluate adherence of Staphylococcus epidermidis to two intraocular lens types--lenses with polypropylene haptic materials and all-polymethyl methacrylate optic and three-piece all-polymethyl methacrylate lenses--using a quantitative culture method, a radioisotope technique, and scanning electron microscopy. All three methods demonstrated approximately twice as many bacteria adherent to lenses with polypropylene haptic materials as to all-polymethyl methacrylate lenses. Scanning electron microscopy showed preferential bacterial adherence to the polypropylene haptic materials. These data provide a pathogenic mechanism to explain our epidemiologic findings of an increased risk of postoperative endophthalmitis associated with implantation of intraocular lenses with polypropylene haptic materials. PMID- 8431165 TI - Microwave diathermy of the retina and choroid. AB - Microwaves were used to induce chorioretinal scar formation in normal rabbit eyes. We have developed a directional 6.8-gigahertz microwave applicator with a rectangular aperture. It was designed to mimic the shape and function of a T shaped scleral depressor. For treatment, the applicator was placed on the conjunctiva over the sclera. Then, indentation was used to visualize probe placement during indirect ophthalmoscopy. Thermocouple-controlled heating was initiated such that conjunctival temperatures in a range of 51 degrees C to 65 degrees C were induced for 10 seconds per treatment. We found that treatment at temperatures of 51 degrees C or 52 degrees C for 10 seconds produced circular areas of acute retinal whitening. From these microwave-induced lesions, there evolved chorioretinal attenuation with and without evidence of retinal pigment epithelial hyperplasia. No evidence of scleral damage was noted at these thermal doses. PMID- 8431166 TI - Evaluating the reproducibility of topography systems on spherical surfaces. AB - Newly devised software was used to compare the ability of the Topographic Modeling System-1 (Computed Anatomy, New York, NY) and the Corneal Analysis System (EyeSys Laboratories, Houston, Tex) to reproduce power measurements on spherical surfaces. Reproducibility results were compared for spheres of 40.00, 42.50, and 44.00 diopters. The program determines the absolute difference in corneal power at defined keratoscope positions for paired examinations of the same eye. Four examinations of each sphere were obtained with each instrument. Individual points were sampled at specific keratoscope locations at 30 degrees semimeridional intervals. The program compared variability of measurements at four defined ranges of distance from the vertex normal: within 0.60 mm, 0.61 to 1.5 mm, 1.51 to 2.5 mm, and 2.5 mm or greater. The Corneal Analysis System showed significantly greater variability of readings obtained within 0.60 mm of the vertex normal for all three spheres (P = .001 by Duncan's multiple comparison procedure), whereas the Topographic Modeling System-1 showed equally consistent readings within 0.60 mm as it did between 0.61 and 1.5 mm from the vertex normal. PMID- 8431167 TI - Prolonged localized tissue effects from 5-minute exposures to fluorouracil and mitomycin C. AB - Rabbits undergoing full-thickness glaucoma filtering surgery were exposed for 5 minutes to one of three intraoperative treatments: (1) distilled water; (2) fluorouracil, 50 mg/mL; or (3) mitomycin C, 0.4 mg/mL. Tissue samples were taken from the subconjunctival and scleral tissues at the treated area and 90 degrees and 180 degrees from the center of the treated area and the adjacent cornea 2 mm from the limbus, 1 hour, 5 days, and 30 days postoperatively. The biopsy specimens were then placed in tissue culture media and the fibroblast outgrowths measured. Five-minute intraoperative treatments with fluorouracil resulted in a reversible delay of fibroblast outgrowths from treated subconjunctival and scleral tissues of just over 1 week in this model, whereas treatment with mitomycin C, 0.4 mg/mL, resulted in prolonged inhibition of at least 30 days. These effects were localized to the area treated. The many clinical implications of these findings are discussed. PMID- 8431168 TI - Thrombosis of the lateral transverse sinus with papilledema. PMID- 8431169 TI - Benign breast disease. A practical guide. AB - A concise working guide to the syndrome of benign breast disorder is given for the busy general practitioner. An outline of the symptoms, current thoughts on pathophysiology and recommendations for treatment are discussed. PMID- 8431170 TI - Radiology and the breast. AB - Mammography should be able to: Detect a high proportion of breast cancers well in advance of any other alternative currently available, and with good positive and negative predictive values. Provide access to impalpable lesions. Offer valuable information in many cases about the tumour, and useful correlation with clinical and pathological findings. Mammography can not: Find all breast cancers. Up to three per cent of even advanced cancers may be missed, especially those of the invasive lobular type. Offer close pathological correlation where the mammographic appearances are indeterminate or non specific. The role of mammography in benign breast disease or the role of radiological modalities other than mammography in the staging and follow up of diagnosed breast cancer has not been discussed. There is nevertheless a mounting excitement within the radiology community that in the absence of useful preventive measures to control the devastating effects of breast cancer, early and accurate diagnosis is the best we can do. The films must be of excellent quality and must be interpreted by experienced people with common sense, an openness to continuing education and a committed desire to do the best for every woman. PMID- 8431171 TI - Treatment options for breast cancer. AB - Breast cancer management has been made difficult by well meaning experts who, by their breadth of knowledge, have created an exclusive jargon. The sad fact is that no real advance in the treatment of the disease has been made. The guidelines in this article derive from a document written by The South Australian Breast Cancer Study Group and represent the views of the majority of doctors who have a special interest in the diagnosis and treatment of breast cancer. PMID- 8431172 TI - Discovering a breast lump. Management plans and pitfalls. AB - The author aims to help general practitioners assess a palpable breast lump by reinforcing standard procedures. Common pitfalls and difficulties of presentation and investigation are highlighted. PMID- 8431173 TI - Breast cancer. Incidence, mortality and prospects for control. AB - Breast cancer is the commonest cancer affecting women in Australia and in most other countries where adequate data are collected. Although mortality rates from breast cancer have changed little in the past 60 years its incidence is increasing and it therefore remains a significant public health problem. This article summarises epidemiological data and prospects for reducing mortality rates from the disease. PMID- 8431174 TI - Patient education. Gallstones. PMID- 8431176 TI - Milestones. To be read while listening to Vivaldi's Four Seasons. PMID- 8431175 TI - Dr Ian Steven. A scholarly GP. AB - Ian Steven MB, BS (Adelaide), MD, FRACGP, FAFPHM, a general practitioner in Collinswood, South Australia, has an outstanding record in scholarship and research. Apart from achieving an MD in 1984 he has been awarded the Wellcome Prize for Research on two occasions and the F H Faulding Memorial Fellowship on two occasions. He is the Director of the Research and Health Promotion Unit of the RACGP and is a member of several research and medical advisory groups. Another outstanding achievement was his record breaking success on the television programme 'Sale of the Century'. PMID- 8431177 TI - Good grips for reduction of dislocated digits. PMID- 8431178 TI - Intralesional corticosteroids for orf. PMID- 8431179 TI - Homosexual statistics. PMID- 8431180 TI - Measuring 'intangibles'. PMID- 8431181 TI - Reducing deaths from breast cancer. PMID- 8431182 TI - The effects of brace position on injuries sustained in the M1 Boeing 737/400 disaster, January 1989. NLDB Study Group. AB - Of the initial 87 survivors of the East Midlands Boeing 737/400 aircraft, 77 sustained head and facial trauma during the crash, 45 of whom were rendered unconscious. There were 21 who received injuries to the back of their head, including 5 of the 6 severely head-injured adults. Those passengers who adopted the fully flexed "brace" position for crash-landing achieved significant protection against head injury, concussion, and injuries from behind irrespective of local aircraft structural damage. A computer graphics simulation developed by a commercial firm (H. W. Structures, Ltd.) using the predicted crash pulse of the accident has validated these clinical findings and allows theoretical biomechanical modeling for the design of occupant protection systems in the future. Although the major role of structural failure should not be forgotten, bracing maximizes the chance of uninjured survival in the current generation of aircraft and should be demonstrated and practiced as a pre-flight routine. PMID- 8431183 TI - Diazepam as a treatment for nerve agent poisoning in primates. AB - Diazepam is known to decrease organophosphate nerve agent-induced convulsions, neuropathology, and lethality in rhesus monkeys. We report that, when added to the previously fielded treatment regimen (pyridostigmine, atropine, and pralidoxime chloride), diazepam significantly protects the performance of rhesus monkeys trained in an equilibrium task, the Primate Equilibrium Platform (PEP), against deficits induced by the nerve-agent soman. If administered soon enough to minimize the occurrence of convulsions, diazepam should increase the probability of mission accomplishment and eventual complete recovery from nerve agent poisoning. Diazepam was fielded by the United States military services during Operations Desert Shield and Storm for the treatment of possible organophosphate toxicity. PMID- 8431184 TI - Influence of stress on lymphocyte subset distribution--a flow cytometric study in young student pilots. AB - Stressors can induce sizable modifications on immunocompetent cells. Major circulating lymphocyte subsets were quantitated in Italian Air Force student pilots undergoing intensive training and continuous evaluation, a stressful situation both physically and psychologically. Instructor pilots matched for age and assayed in parallel were used as controls. A typical flight training session was not able per se to induce immediate significant modifications of the lymphocyte subset distribution either in the students or instructors, although it did affect plasma levels of stress-related hormones such as growth hormone, prolactin and cortisol in the former. Irrespective of the time of flying, however, the percentage of CD4+ lymphocytes and the CD4/CD8 ratio were lower in students than in instructors, and the absolute number of CD8+ lymphocytes was higher in students than in instructors. In a second series of experiments, 30 student pilots were tested at the beginning and at the end of a flight course (duration 30 days). Although the percentage of CD29+ lymphocytes comprised in the CD8+ subset was reduced at the end of the course in all individuals, such a reduction was more evident in those students who failed to pass the final examination, an additional cause of psychological stress. In light of the functional significance of the lymphocyte subsets investigated, it is suggested that the present stress-induced alterations may have practical implications. PMID- 8431185 TI - Bubble formation and decompression sickness on direct ascent from shallow air saturation diving. AB - To find the minimum supersaturation pressure for detectable bubble formation and for contraction of decompression sickness (DCS), three shallow air saturation dives at the depth of 6 m, 7 m, and 8 m were performed. The ultrasonic M-mode method was used for detecting bubbles. The exposure period was 3 d for all dives. Ten subjects were compressed to both 6 m and 7 m, and nine subjects were compressed to 8 m. One bubble streak was shown in the 6-m dive group. A small number of bubbles were seen in four subjects in the 7-m dive. All subjects in the 8-m dive presented various amounts of bubbles. DCS was not observed in the 6-m and 7-m dives. On the other hand, in the 8-m dive, four subjects suffered from DCS and required recompression treatment. The minimum depth for detectable bubble formation was assessed at around 6 m and the direct ascent from saturation at 8 m seems to have a high risk of DCS. PMID- 8431186 TI - The effects of variations in the anti-G straining maneuver on blood pressure at +Gz acceleration. AB - The increase in blood pressure provided by the standard AGSM is caused by both the contraction of the muscles of the lower body and by an increased intrathoracic pressure due to a respiratory straining (Valsalva) maneuver. This study examined the relative effectiveness and fatigability of the two components at +1 Gz and during +Gz acceleration in a human centrifuge. Brachial arterial pressure was recorded from a pressure-tip transducer in six subjects performing isometric leg presses only and on a separate occasion while performing respiratory straining only. Measurements were made over a range of intensities for the leg press contractions and Valsalva maneuvers and were conducted at +1 Gz and during slow and rapid onset runs up to +5 Gz in a human centrifuge. Blood pressure was also recorded during pulsing or intermittent contractions of the legs. We found it difficult to completely separate the blood pressure response to the leg press component from that of the respiratory straining alone component, since a moderate respiratory straining maneuver usually accompanied forceful contractions of the legs. We conclude, however, that a major portion of the elevation in blood pressure caused by the AGSM can be attributed to contraction of the muscles of the lower body and that this component is less fatiguing than the respiratory straining component. At +1 Gz a pulsing isometric contraction of the legs was no more effective in elevating blood pressure than a constant isometric contraction over the same duration. PMID- 8431187 TI - The effect of G-LOC on psychomotor performance and behavior. AB - Acceleration (+Gz) induced loss of consciousness (G-LOC) and its effect upon cognitive and motor performance were evaluated in seven male volunteers who were exposed to closed-loop acceleration exposures at the Naval Air Warfare Center- Aircraft Division, Warminster (NAWCADWAR) human centrifuge (DFS). The +Gz profile consisted of several aerial combat environment simulations (ACES) of up to +12 Gz. In the event of G-LOC, the DFS was brought down to a base +Gz level. As the subject recovered consciousness, he was required to complete various tasks to regain control of the aircraft. Psychomotor performance was measured before, immediately after, and 20-40 min post-G-LOC. These tasks included: 1) extinguishing master caution signals initiated upon G-LOC by an observer; 2) entering a control code on a head-down display to initiate DFS trim mode; and 3) matching own aircraft altitude, airspeed and heading to that of a displayed target. Absolute (6 +/- 2 s), relative (5 +/- 3 s) and total (12 +/- 3 s) incapacitations were briefer than those reported in the literature. The time intervals to execute the performance tasks tended to be longer for post-G-LOC than for pre-G-LOC. Recovery of psychomotor performance, as measured in this study, occurred approximately 60 s post G-LOC. There were no performance decrements during those tasks assigned 20-40 min after G-LOC. PMID- 8431188 TI - Blood volume reduction counteracts fluid shifts in water immersion. AB - Six healthy men were bled by 15% of their total blood volume (TBV) before 7 h of seated water immersion to test the hypothesis that some of the major physiological responses to an expansion of central blood volume can be counteracted by prior reduction of TBV. Subjects were their own controls under two conditions: seated dry in air and seated immersed to the suprasternal notch in water. Immersion without prior reduction of TBV (WC = Wet Control) caused a statistically significant 22% increase in cardiac output (CO), 368% increase in urine production, and 200% increase in sodium excretion relative to dry control (DC) sessions. When TBV was reduced before immersion, CO was the same as during DC sessions; however there were significant increases above DC in urine flow (+73%) and sodium excretion (+120%), although they were significantly reduced from WC values. Potassium excretion was similar during DC and WC sessions, but was significantly increased (+75%) when subjects were immersed after 15% reduction of TBV. PMID- 8431189 TI - Preliminary analysis of sensory disturbances and behavioral modifications of astronauts in space. AB - Behavioral modifications of astronauts over time spent in microgravity conditions was investigated according to an ethological approach based on video recordings during the Spacelab-1 mission. The method consisted of a description and a quantification of motor activity of a subject (movement and orientation) while performing working tasks. Each period of observation lasted 20 min, on days 1, 2, 3, 4, 7, 9, and 10. This provided a rather consistent frequency for behavioral sampling. The data were correlated with the findings of physiological experiments performed during the same spaceflight. Results revealed an increase in frequencies of certain motor outputs (e.g., yaw head and body movements, hand gripping, feet anchoring) which favored several specific sensory inputs (visual and tactile information). In addition to the appearance of head-down orientations while manipulating floating objects and during periods of body free-floating, the astronaut developed a new representation of the space and the objects around him in microgravity. These behavioral interpretations are discussed in the light of sensorimotor interactions and cognitive events. PMID- 8431190 TI - Study design for microgravity human physiology experiments. AB - In some areas of research, such as microgravity life sciences, both the number of subjects and the opportunity for repeated observation under experimental conditions are limited. Small N study designs are appropriate for these situations since they require few subjects and few observations in the experimental condition. Small N studies compare treatment conditions separately for each subject so that between-subject variability does not obscure treatment effects. Multiple observations are collected for each individual in the baseline condition to ensure a stable reference point for comparison with the smaller number of observations collected under the experimental conditions. Individual differences can be overlooked in large N studies, but in small N studies the focus is on the individual, and differences observed between particular individuals can be suggestive of underlying causal processes. We present a step by-step approach to designing and conducting a small N study. PMID- 8431191 TI - Measuring performance decrements in aviation personnel infected with the human immunodeficiency virus. AB - There is controversy over whether cognitive impairment occurs in early human immunodeficiency virus (HIV) disease. When impairment is reported, findings are typically subclinical, affect only a minority, and their relationship to occupational functioning has not been established. Despite such findings, it has been recommended that HIV-seropositive pilots be disqualified from flying. This paper reviews research relevant to measuring performance decrements in HIV infected aviators. Based upon current data, we conclude that although subtle neurobehavioral dysfunction may occur in some asymptomatic HIV-seropositive individuals, there is no research which has demonstrated associated decrements in aviation-related skills. Thus, it may be premature to recommend medical disqualification of all HIV-seropositive aviators. We propose, instead, that sensitive neurocognitive measures, incorporated into a comprehensive neurodiagnostic evaluation, could be used to evaluate asymptomatic HIV seropositive aviators. Only those who are impaired on evaluation would be disqualified from flying. Concurrently, research investigating the relationship between abnormalities and aviation abilities would be conducted. PMID- 8431192 TI - Lower body negative pressure system for simulation of +Gz-induced physiological strain. AB - Lower body negative pressure (LBNP) can be considered as an experimental substitute for the +Gz stress. In military aviation, pilots assume a near upright position and are subjected to +Gz stress in this position. An LBNP chamber has been developed in which negative pressure can be applied to the subject in the upright seated position. The chamber is easy to fabricate and can be used to assess the tolerance of subjects likely to be exposed to high levels of +Gz stress. PMID- 8431193 TI - You're the flight surgeon. Environmental heat stress. PMID- 8431194 TI - Asymptomatic HIV-1 infection and aviation safety. PMID- 8431195 TI - Neck injuries in aviators flying high performance aircraft. PMID- 8431196 TI - The effects of structural failure on injuries sustained in the M1 Boeing 737 disaster, January 1989. NLDB Study Group. AB - Only 10 occupants escaped uninjured from the wreckage of the East Midlands Boeing 737/400 aircraft accident. The remaining 116 suffered injuries similar in pattern, but ranging in severity from simple bruising to fatal crushing trauma. Overall, the individual's degree of injury and likelihood of death was proportional to the local structural damage of the aircraft. Limb injuries were particularly severe in the forward section of the wreckage where the floor failed. In areas where structural damage appeared to be survivable, a number of passengers suffered disproportionately severe head injuries. Many of these had trauma to the posterior aspect of their head, some of whom died as a result. It is likely that these injuries were caused by falling overhead lockers or unrestrained cabin furniture. The significance of these injuries and their future prevention is discussed. PMID- 8431197 TI - [The occurrence and significance of enterotoxin-producing Clostridium perfringens strains in the intestinal tract of horses]. AB - 100 faecal samples from clinically healthy horses of different age groups and feeding habits, 50 samples of faeces from horses suffering from enteropathy accompanied by diarrhoea and small and/or large intestine from 25 horses that had died after an intestinal disease were examined for the presence of Clostridium (Cl.) perfringens. The frequency with which Cl. perfringens was detected was 22% in clinically healthy horses, 32% in horses with diarrhoea and 52% in the dead horses. In two faecal samples from the horses with diarrhoea the microbial count of Cl. perfringens was ca. 10(6) cfu/g faeces. The occurrence of Cl. perfringens in clinically healthy horses was not influenced by age. In animals fed exclusively on grass silage Cl. perfringens was found more frequently. The enterotoxin of Cl. perfringens was identified in one of 36 faecal samples from horses with diarrhoea. 54 Cl. perfringens strains isolated from material examined were studied for their ability to sporulate and to produce enterotoxin. 98% of the strains formed spores. Enterotoxin production was negative in all cases. Experimental investigations with enterotoxin producing Cl. perfringens strains on four ponies did not show any signs of a possible durable colonization of the intestinal tract by this organism. The results of these investigations do not suggest any pathogenic relevance of enterotoxin producing Cl. perfringens strains to the development of enteropathy in horses. PMID- 8431198 TI - [The concentration of ascorbic acid, total protein, alpha-amino-N, glucose, 3 hydroxybutyrate and cholesterol and the activity of adenosine deaminase in the blood of sheep in five different periods of pregnancy and the content of ascorbic acid in 14 tissues]. AB - Analyses of different compounds in the plasma of healthy sheep before birth were conducted from day 70 to 43 (group 1), 42 to 22 (group 2), 21 to 15 (group 3), 14 to 8 (group 4) and 7 to 1 (group 5). There were significant differences in the concentration of ascorbic acid, total protein, total alpha-Amino-N, glucose, 3 hydroxybutyrate and of adenosine deaminase in the plasma between several groups, their significance is discussed. There was no difference in the concentration of cholesterol in the plasma of the sheep of the 5 groups. The content of ascorbic acid in 14 different tissues of sheep of the age of 6 and 12 months was analysed. There were significant differences between the 2 groups in the levels of ascorbic acid of the cerebrum and cerebellum, the hypophysis, the lungs, the kidneys and the spleen. PMID- 8431199 TI - [Comparison of the career profiles of racehorses over three decades]. AB - To compare the career profiles of thoroughbred racehorses in Germany in different decades all horses which raced for the last time in the years 1966/67, 1976/77 and 1986/87 were selected from the annual report of the German Thoroughbred Racing Association. The number of racing horses increased within decades while the percentage of the horses which raced for the last time was equal in all years. It amounted yearly to about 30%. Most of the horses finished racing at three and four years of age. In 1966, 1967, 1976 and 1977 more than 50% of the horses began their career at the age of two years, while in 1986 and 1987 the rate was below 50%. The duration of the career depended on the age at the first race and the gender. Colts and geldings raced an average of 3.5 and 4.3 years respectively, fillies 2.7 years. The average of races during the career remained constant during each decade at 27 and 35 for the colts and geldings respectively, while for the fillies it decreased from 24 races in 1966/67 to 20 races in 1986/87. PMID- 8431200 TI - [Thiocyanate blood levels in roe deer, red deer, fallow deer and wild boar]. AB - The following serum levels of thiocyanate (SCN-) were found in game: roe 6.6 +/- 4 mg/l, red deer 5.5 +/- 3.2 mg/l, fallow-deer 5.1 +/- 2.8 mg/l, and wild boar 4.8 +/- 4.5 mg/l (variation 0.6-32.6 mg SCN-/l). These levels are distinctly higher than in domestic animals under stall-feeding with exception of mast calves which were fed milk-substitutes. The SCN- serum level of calves, sheep and horses reach at pasturing nearly the level of game. The higher SCN- serum level of cloven-hoof game resp. by pasturing of domestic animals is caused by higher alimentary SCN- intake. PMID- 8431201 TI - [Myopathy due to potassium deficiency in eight cats and a dog]. AB - Eight cats and one dog with signs of cervical ventroflexion, reluctance to walk, a stiff and stilted gait and muscle weakness are introduced. Though blood potassium concentration was very low (< 3.0 mval/l) in one cat and the dog only, a potassium depletion myopathy was assumed as the cause of these symptoms. Two of three cats had elevated values of the urinary fractional potassium excretion compared to ten healthy cats. Blood creatinine values were within normal ranges. Five of seven cats had elevated creatine kinase values. All animals improved after potassium substitution. Causes of potassium depletion are discussed and differential diagnoses of myopathies are briefly mentioned. PMID- 8431202 TI - [The effectiveness of tilmicosin in respiratory diseases of swine]. AB - Within the scope of the clinical evaluation of Tilmicosin in Enzootic Pneumonia of pigs, nasal swabs from 78 animals were taken, before and after oral medication of different doses (0, 100, 200, 300 mg Tilmicosin/kg dry food), and examined bacteriologically for Pasteurella multocida, Bordetella bronchiseptica und Haemophilus parasuis. The bacteria aforementioned were isolated from the nasal secretions of 83% of the pigs, 14 days after crowding without any prophylactic regime. It could be demonstrated, that pigs with clinical symptoms of Enzootic Pneumonia had a 50% higher prevalence-rate of multi-colonization with pneumotropic bacteria than healthy animals. Feeding 300 mg Tilmicosin/kg food for 9 and 14 days respectively, resulted in elimination of Pasteurella spp. and Haemophilus spp. The rate of newly Bordetella bronchiseptica infected pigs was lower than in the placebo-group. Parallel to these bacteriological results improvement of clinical signs and increased daily weight gain were observed. PMID- 8431203 TI - The adhesion molecules of inflammation. PMID- 8431204 TI - Interleukin-1-mediated phospholipid breakdown and arachidonic acid release in human synovial cells. AB - OBJECTIVE: Interleukin-1 (IL-1), an important mediator contributing to joint destruction in rheumatoid arthritis, is known to stimulate the release of arachidonic acid (AA) and prostaglandin E2 (PGE2) from adherent synoviocytes. To study the intracellular pathways involved in these functions, we stimulated cultures of human synovial cells with recombinant IL-1 beta. METHODS: AA liberation was measured after labeling synovial cells with 3H-AA, and PGE2 levels were determined by high performance liquid chromatography or radioimmunoassay. Identification of 3H-AA-labeled phospholipids was performed by thin layer chromatography. Cell-associated phospholipase A2 (PLA2) enzymatic activity was determined by an assay with cell-free systems and exogenous substrates. RESULTS: Stimulation of synovial cells with recombinant IL-1 beta induced a decrease in phosphatidylcholine (PC), phosphatidylinositol (PI), and phosphatidylethanolamine (PE), and a marked increase in cell-associated PLA2 activity as compared with controls. In the presence of either quinacrine, an inhibitor of PLA2 pathway activation, or neomycin, which binds to PI mono- and biphosphate thus blocking their degradation by phospholipases, AA and PGE2 secretion were reduced in a dose dependent manner. Kinetic studies revealed that quinacrine had little blocking activity on the IL-1-mediated AA release after 1 hour of stimulation but completely abolished it after 5 or 8 hours. In contrast, neomycin exerted a partial but significant inhibitory effect from the first hour of stimulation onward. Addition of quinacrine was also demonstrated to abolish the IL-1-induced hydrolysis of PC and PE but not PI, indicating that PC and PE are the preferred substrates for PLA2 enzymatic activity in human synovial cells. CONCLUSION: Our findings strongly suggest that AA and PGE2 production by IL-1-triggered synoviocytes are largely dependent upon PLA2-mediated hydrolysis of PC and PE and to a lesser extent upon the earlier degradation of PI. PMID- 8431205 TI - Proteolytic inactivation of alpha 1-antitrypsin and alpha 1-antichymotrypsin by neutrophils in arthritic joints. AB - OBJECTIVE: In vitro, activated neutrophils create a microenvironment in which proteinase inhibitors are inactivated through the coordinate action of reactive oxygen species and released elastase. We investigated whether such a mechanism may contribute to the destruction of the joint tissues in arthritis. METHODS: We analyzed the state of alpha 1-antitrypsin (alpha 1AT) and alpha 1 antichymotrypsin (alpha 1ACT), the two major inhibitors of the neutrophilic serine proteinases, in synovial fluid (SF) from patients with inflammatory arthropathies (n = 71) and osteoarthritis (OA) (n = 11), and related the results to neutrophil activation in SF. RESULTS: The ratio of functional to antigenic levels of alpha 1AT in SF of patients with inflammatory joint diseases was similar to that of alpha 1AT in normal plasma, whereas that of alpha 1ACT was significantly decreased. Patients with inflammatory arthropathies had significantly higher levels of inactivated alpha 1AT (i alpha 1AT) and inactivated alpha 1ACT (i alpha 1ACT) in SF (as determined with monoclonal antibodies specific for the inactivated [i.e., proteolytically inactivated and/or complexed] forms of these inhibitors) than patients with OA (P < 0.005). Inactivated alpha 1AT and i alpha 1ACT levels corresponded to 0.3-11% and 3-99%, respectively, of the total amount of these inhibitors in SF. Most of the i alpha 1AT in SF had a lower M(r) than that of native alpha 1AT. Inactivated alpha 1ACT in SF had an M(r) identical to that of nonfunctional alpha 1ACT in plasma treated with chymotrypsin. Levels of both i alpha 1AT and i alpha 1ACT correlated significantly with lactoferrin and elastase levels. CONCLUSION: These results suggest that alpha 1AT and alpha 1ACT in arthritic joints are inactivated in part by activated neutrophils, suggesting a role for these cells in impairment of the local balance between proteinases and their inhibitors in arthritis. PMID- 8431207 TI - Phospholipase A2 and arthritis. AB - Over the last 30 years, interest in PLA2 has grown beyond its enzymatic capacity to cleave phospholipids. It has been recognized as the rate-limiting step in the release of arachidonic acid and subsequent formation of prostaglandins, leukotrienes, and other bioactive lipids. Subsequently, PLA2 has not only been found to be present in high concentrations in inflammatory arthritis, but also to induce inflammation when injected into animals. At the same time, investigators into mechanisms of signal transduction demonstrated that a variety of cytokines including IL-1 and TNF, which are found in high concentrations in synovial fluid from patients with RA, stimulate PLA2 activity. These investigations demonstrated further the central role for PLA2 in inflammatory events, especially inflammatory arthritis. Numerous other PLA2 proteins, in addition to the low molecular weight synovial fluid/platelet enzyme, also have been characterized. Their clinical role in arthritis is yet to be elucidated. Human proteins which either inhibit or stimulate PLA2 have also been identified, characterized, and cloned. More recently, exciting investigations, primarily from biotechnology and pharmaceutical companies, into inhibitors of PLA2 have been reported. New PLA2 regulating compounds, which will hopefully move from the laboratory and through clinical trials and then be used to treat patients with arthritis, are on the horizon. PMID- 8431206 TI - Metalloproteinases, tissue inhibitor, and proteoglycan fragments in knee synovial fluid in human osteoarthritis. AB - OBJECTIVE: To determine the concentrations of human stromelysin-1, collagenase, tissue inhibitor of metalloproteinases (TIMP), and proteoglycan fragments in knee synovial fluid in patients with injury to the meniscus or anterior cruciate ligament, posttraumatic osteoarthritis, primary osteoarthritis, or pyrophosphate arthritis. METHODS: Synovial fluid samples were collected from patients with knee disease diagnosed arthroscopically and radiologically. Concentrations of stromelysin-1, collagenase, and TIMP-1 were determined by sandwich immunoassay, using monoclonal and polyclonal antibodies. Fragments of cartilage proteoglycan containing the chondroitin sulfate-binding region were determined by immunoassay with a polyclonal antibody. RESULTS: Average concentrations of metalloproteinases, TIMP, and proteoglycan fragments in joint fluid were significantly elevated in patients from all disease groups as compared with volunteers with healthy knees (reference group). Stromelysin concentrations in disease groups averaged 15-45 times that of the reference group. The molar ratios between stromelysin and collagenase varied between 10 and 150. The molar ratio between total stromelysin and free TIMP was 0.5 in the reference group and between 1.6 and 5.3 in the disease groups. CONCLUSION: Stromelysin concentration in joint fluid is a parameter that distinguishes diseased joints from healthy joints, with a sensitivity of 84% and a specificity of 90%. The high concentrations of metalloproteinase relative to TIMP in joint fluid from patients with the conditions studied may be associated with cartilage matrix degradation in these arthritides. PMID- 8431208 TI - Temporal covariation of soluble interleukin-2 receptor levels, daily stress, and disease activity in rheumatoid arthritis. AB - OBJECTIVE: To examine synchronous changes in soluble interleukin-2 receptor (sIL 2R) levels, daily indicators of emotional stress, joint inflammation, and reported pain in patients with rheumatoid arthritis (RA). METHODS: Fourteen patients were studied on each of 6 occasions, 2 weeks apart. Measures included daily ratings of mood disturbance, undesirable events, and joint pain; clinical examination of joint swelling; and serum assays of sIL-2R. Pooled within-person correlations among these variables were calculated. RESULTS: Consistent with the results of previous research, joint inflammation covaried directly with sIL-2R levels. Changes in mood disturbance were unrelated to changes in joint inflammation, but increases in mood disturbance were linked with decreases in sIL 2R levels and increases in reported joint pain. CONCLUSION: These findings provide preliminary evidence that psychoimmune processes may be implicated in short-term changes in RA disease activity. PMID- 8431209 TI - Stress and the immune system: preliminary observations in rheumatoid arthritis using an in vivo marker of immune activity. PMID- 8431210 TI - Suppression of interleukin-2 and interleukin-2 receptor biosynthesis by gold compounds in in vitro activated human peripheral blood mononuclear cells. AB - OBJECTIVE: To further investigate the mechanism of action of gold compounds by studying their effects on interleukin-2 (IL-2) and IL-2 receptor (IL-2R) biosynthesis. METHODS: We cultured phytohemagglutinin- or anti-CD3 antibody activated normal peripheral blood mononuclear cells (PBMC), as well as the erythroleukemic K562 cell line, in the presence of gold sodium thiomalate or auranofin. Tritiated thymidine incorporation assays, cytotoxicity assays, immunofluorescence analysis, enzyme-linked immunosorbent assay, Northern blot, and RNA dot-blot hybridization were used. RESULTS: Gold compounds, at concentrations attainable in vivo, inhibited the proliferation of normal PBMC, with no evidence of direct cytotoxicity. This inhibitory effect was associated with a dose-dependent suppression of both IL-2 and IL-2R messenger RNA accumulation. In contrast, the same concentrations of gold compounds failed to inhibit the spontaneous proliferation of the IL-2-independent K562 cells. CONCLUSION: Our findings suggest an IL-2/IL-2R-mediated mechanism for suppression of lymphocyte proliferation by gold compounds, which might account for the immunomodulatory effects of gold in patients with rheumatoid arthritis. PMID- 8431211 TI - Divergent T cell receptor gamma repertoires in rheumatoid arthritis monozygotic twins. AB - OBJECTIVE: To determine if the expressed T cell receptor (TCR) gamma repertoire is altered in rheumatoid arthritis (RA). METHODS: Peripheral blood lymphocytes were collected from monozygotic twins who were either concordant or discordant for RA, or from a normal twin pair. TCR gamma-specific complementary DNA libraries were constructed using the anchored polymerase chain reaction. Gene usage was analyzed by plaque hybridization and sequencing. RESULTS: The expressed TCR V gamma repertoires both in RA patients and normal subjects were extremely diverse. Monozygotic twins who were concordant for RA expressed very different frequencies of TCR V gamma genes. CONCLUSION: RA does not lead to a specific clonal expansion or deletion of TCR V gamma genes in peripheral blood. PMID- 8431212 TI - Bone mineral density of the hip and of the anteroposterior and lateral dimensions of the spine in men with rheumatoid arthritis. Effects of low-dose corticosteroids. AB - OBJECTIVE: To assess bone mineral density (BMD) in men with steroid-treated rheumatoid arthritis (RA). METHODS: Dual-energy x-ray absorptiometry (DXA) was used to measure BMD in 40 men with RA, 20 of whom were receiving low-dose corticosteroids (< or = 10 mg prednisolone daily), and in 20 healthy, age-matched male controls. RESULTS: BMD was significantly reduced at the femoral neck and greater trochanter in both groups of RA patients, and at the spine from the anteroposterior dimension in the steroid-treated group. CONCLUSION: Low-dose steroid therapy may induce excess axial osteopenia in men with RA. PMID- 8431214 TI - Effects of hyaluronic acid on the release of proteoglycan from the cell matrix in rabbit chondrocyte cultures in the presence and absence of cytokines. AB - OBJECTIVE: To investigate the effects of hyaluronic acid (HA) on the release of proteoglycan by cultured rabbit chondrocytes. METHODS: Articular cartilage chondrocytes were isolated from the knee joints of New Zealand white rabbits. Proteoglycan synthesis after incubation with HA was determined by measuring 35S sulfate incorporation. Cells incubated with HA were labeled with 3H-glucosamine and applied to a Sepharose CL-2B column. After incubation of confluent cells with 35S-sulfate and then with HA in various concentrations in the presence or absence of cytokines, proteoglycan release from the cell matrix layer was measured. RESULTS: HA (M(r) 3 x 10(5) to 19 x 10(5)), at 10 micrograms/ml to 1 mg/ml, had little effect on the incorporation of 35S-sulfate or 3H-glucosamine into cartilage matrix proteoglycans, or on the hydrodynamic size of proteoglycan monomers, in rabbit chondrocyte cultures. However, at 10-1,000 micrograms/ml, HA suppressed the release of 35S-proteoglycans from the cell matrix layer into the medium in the presence and absence of interleukin-1, tumor necrosis factor alpha, or basic fibroblast growth factor. CONCLUSION: These results suggest that HA is a potent inhibitor of the displacement of matrix proteoglycan into culture medium. PMID- 8431213 TI - Increased production of soluble CD23 in rheumatoid arthritis, and its regulation by interleukin-4. AB - OBJECTIVE: To assess CD23 status in rheumatoid arthritis (RA) patients, as defined by the levels of CD23 expression on peripheral blood mononuclear cells (PBMC), the levels of soluble CD23 (sCD23) in sera, and the production of sCD23 by PBMC cultures and its regulation by interleukin-4 (IL-4). METHODS: CD23 expression as determined by double fluorescence-activated cell sorter analysis and sCD23 production as determined by immunoradiometric assay were investigated in 24 RA patients and 21 controls. Soluble CD23 was measured in sera and supernatants of PBMC, activated with polyclonal activators (pokeweed mitogen [PWM] or Staphylococcus aureus Cowan strain 1, [SAC]) used either alone or in combination with IL-2 or IL-4. RESULTS: The percentage of B cells expressing CD23 and serum levels of sCD23 were increased in patients with RA. IL-4 was a potent inducer of sCD23 production in supernatants, whereas IL-2 was inactive. Costimulation with SAC or PWM did not increase the effect obtained with IL-4 alone. When sCD23 levels in RA and control supernatants were compared, spontaneous production was found to be increased in RA PBMC: This difference from control values was even more pronounced when sCD23 levels in PBMC and purified B cells in response to IL-4, either alone or in combination with SAC or PWM, were tested. In the same supernatants, the increased secretion of sCD23 induced by IL 4 was associated with an inhibitory effect of IL-4 on Ig production, a phenomenon that was more pronounced in RA PBMC than in controls. CONCLUSION: CD23 status in RA is characterized by increased expression of CD23 on B cells, increased production of sCD23 in sera and supernatants, and increased sensitivity of RA PBMC and B cells to IL-4. PMID- 8431215 TI - Induction of autoimmune arthritis in rats by immunization with homologous rat type II collagen is restricted to the RT1av1 haplotype. AB - OBJECTIVE: To test for genetic differences in susceptibility to homologous (rat) type II collagen-induced arthritis (RII-CIA). METHODS: Nine inbred and RT1 congenic rat strains were immunized with native rat type II collagen and evaluated for arthritis and IgG anti-RII serum antibody titers. RESULTS: Only RT1av1 strains developed a high incidence of severe RII-CIA and high titers of IgG anti-RII serum antibody. Rats having RII-CIA-resistant haplotypes, RT1u,n,l (which are known to develop CIA after immunization with heterologous type II collagen), were shown to also be susceptible to passive transfer of CIA with immune serum concentrates. Clinical expression of RII-CIA was down-regulated by non-RT1 genes of BN origin. No strong gender differences in anti-RII autoimmune responses were observed. CONCLUSION: Arthritogenic, autoimmune reactivity to homologous RII is under strict genetic control but occurs readily in RT1av1 rats. PMID- 8431216 TI - Complete heart block and seizures in an adult with systemic lupus erythematosus. A possible pathophysiologic role for anti-SS-A/Ro and anti-SS-B/La autoantibodies. AB - OBJECTIVE: To determine the serum autoantibody profile in an adult patient with systemic lupus erythematosus manifested by complete heart block (CHB) and seizures, and to investigate the source of autoantibodies found in the patient's cerebrospinal fluid (CSF). METHODS: The serum and CSF autoantibody profiles were determined by serologic testing and Western blot studies. An antibody activity index was devised to determine the source of the autoantibodies found in the CSF. RESULTS: The patient's serum contained anti-SS-A (52 kd and 60 kd), anti-SS-B, anti-U1 RNP, and anti-Sm autoantibodies. Studies of her CSF, however, revealed only anti-SS-A and anti-SS-B autoantibodies, with a high antibody activity index. CONCLUSION: The finding of anti-SS-A (52 kd and 60 kd) and anti-SS-B autoantibodies was similar to reported findings in congenital CHB. Intrathecal synthesis of anti-SS-A and anti-SS-B was the source of autoantibodies found in the CSF. This patient's symptoms may be pathophysiologically linked to an immune reaction between the anti-SS-A and anti-SS-B autoantibodies and neural tissue in the brain and heart. PMID- 8431217 TI - Prevention of autoimmune inflammatory polyarthritis in male New Zealand black/KN mice by transplantation of bone marrow cells plus bone (stromal cells). AB - OBJECTIVE: To prevent polyarthritis in male New Zealand black/KN (NZB/KN) mice by transplantation of both bone marrow cells (BMC) and bone (to recruit stromal cells) from normal mice. METHODS: Arthritic lesions in male NZB/KN mice injected intravenously with BMC plus bone from C57Bl/10 mice were compared with those in untreated male NZB/KN mice. RESULTS: Male NZB/KN mice engrafted with BMC plus bone were both radiologically and histopathologically normal, and had decreased production of anti-single-stranded DNA antibodies and rheumatoid factors at 8-12 months of age. CONCLUSION: Bone marrow transplantation prevented polyarthritis in male NZB/KN mice. PMID- 8431218 TI - A unique presentation of multicentric reticulohistiocytosis in pregnancy. AB - We describe a patient with multicentric reticulohistiocytosis who presented, during the second trimester of pregnancy, with symmetric polyarthritis, marked erythematous, pulsatile synovial swelling of the distal interphalangeal joints of both hands, and widespread telangiectasias. She did not have the typical skin manifestations of multicentric reticulohistiocytosis. The erythema and pulsatility of the synovial swellings of the distal interphalangeal joints resolved after delivery, but she continued to have widespread active synovitis, which did not resolve until treatment with low-dose oral methotrexate was instituted. PMID- 8431219 TI - Ossification of the posterior longitudinal ligament in the cervical spine. PMID- 8431220 TI - Appearance of anti-DNA antibodies in patients treated with interferon-alpha. PMID- 8431221 TI - Informed consent in the use of blood samples from healthy children. PMID- 8431222 TI - Proposal for change to address the rheumatology manpower shortage: a community rheumatologist's response to the editorial by Stross. PMID- 8431223 TI - Rheumatology training for rheumatology fellows and nonrheumatologists: comment on the editorial by Stross. PMID- 8431224 TI - Of names and abbreviations. PMID- 8431225 TI - Impaired osteophyte formation and ankylosing hyperostosis in patients with diabetes: comment on the article by Horn et al. PMID- 8431226 TI - The doctor is in. AB - The growing trend toward an overproduction of specialists and an underproduction of generalists (i.e., family physicians, general internists, and general pediatricians) in the United States has prompted many in medicine and academic medicine to endorse the goal that 50% of the United States's physician graduates should be generalists. The author discusses (1) the definition of the term generalist; (2) the number of generalists presently being produced (as estimated by three methods) and why the 50% goal is an informed and reasonable one; (3) changes needed in graduate medical education of the three main categories of generalist physicians; (4) changes needed in medical education; (5) changes needed in the practice environment; and (6) overall implementation strategies and the question of how much the federal government or some central authority should be involved. He concludes by reflecting that the 50% goal is worthwhile, although challenging, and that it is better to have a goal--even if it is not met--then to have no goal at all. PMID- 8431227 TI - Training an appropriate mix of physicians to meet the nation's needs. AB - Although the lack of a national policy on medical manpower has served U.S. medicine well in some ways, it also has created problems, the most important of which is the maldistribution of physicians in the various specialties, with too many specialists and not nearly enough generalists. The author explains why this imbalance is a problem and why it is receiving so much attention, describes three types of forces--economic, practice-related, and scientific--that favor the practice of specialty medicine, and demonstrates that the medical school experience itself may be a critical influence on students' career decisions. He then outlines possible ways to correct the imbalance, both outside and inside academic medicine; for the latter sphere, he proposes five detailed alternative scenarios of how corrective change might come about, which range from doing nothing to making a number of fundamental changes within academic medicine's institutions to having external financial pressures for change brought to bear by the states and the federal government. In conclusion, the author notes that some combination of these scenarios will occur, because spending for medical care in the United States is out of control and cannot be reduced unless the distribution of physicians by specialty is rebalanced to have a much greater percentage of generalists. His hope is that academic medicine will accept this challenge and bring about the best mix of physicians to meet the nation's needs. PMID- 8431228 TI - An approach to training and retaining primary care physicians in rural Appalachia. AB - The West Virginia School of Osteopathic Medicine (WVSOM) educated and retained more primary care physicians for practice in rural Appalachia than did any other U.S. medical school from 1978 through 1990. This article describes the most important methods used at WVSOM to place physicians in rural areas: (1) The school has a focused, achievable mission (to provide primary care physicians who are trained to meet the medical needs of rural Appalachia and to improve the health care of the rural Appalachian population) that is agreed upon by the administration, faculty, and students; (2) it participates in a multistate educational exchange program with a similar mission; (3) it emphasizes personalized and interactive recruiting, admission, and placement processes aimed to attract nontraditional, rural students; (4) it provides early and long-term clinical training in rural sites (both hospitals and physicians' offices); (5) it is dedicated primarily to the education of medical students rather than to research or other goals; and (6) it is a freestanding school in a rural environment. The authors state that although WVSOM is unusual in some respects, at least some of its methods may be useful to other medical schools as they seek to produce more primary care physicians for rural and other underserved areas. PMID- 8431229 TI - Faculty status for clinician-educators: guidelines for evaluation and promotion. PMID- 8431230 TI - Long-term outcomes of innovative curricular tracks used in four countries. PMID- 8431231 TI - Let's say "no" to Canada-bashing. PMID- 8431232 TI - Compressed video for clinical consultation. PMID- 8431233 TI - What our medical students learned when they talked with parents of sick children. PMID- 8431235 TI - A second minority mentorship program. PMID- 8431236 TI - Fostering surgery residents' learning in an ICU rotation. PMID- 8431234 TI - Medical education and the need for greater awareness of Asian Americans' cultural diversity. PMID- 8431237 TI - Influence of candidates' test selection on pass rates on examinations for certification by the Educational Commission for Foreign Medical Graduates. AB - BACKGROUND: Parts I and II of the National Board of Medical Examiners (NBME) examination were first offered to graduates of foreign medical schools in 1989 as an alternative to the Foreign Medical Graduate Examination in the Medical Sciences (FMGEMS). This study was designed to determine whether differences in pass rates and scores were related to differences in the populations selecting one or the other examination. METHOD: (1) Combined pass rates on the FMGEMS and NBME in 1989 and 1990 were compared with pass rates in previous years. (2) The proportion of NBME takers in 1989 was compared with the proportion in 1990. (3) Respective pass rates on the FMGEMS and NBME in the first NBME administration in 1989 were compared with pass rates in 1990. (4) The percentage of repeaters taking the FMGEMS was compared with the percentage taking the NBME in 1989 and 1990. (5) The distribution of repeaters by number of previous takes was compared between the FMGEMS and NBME in 1989 and 1990. RESULTS: (1) Combined pass rates were similar to the pass rates of previous years. (2) The proportion of NBME takers declined in 1990. (3) The pass rates for the FMGEMS were higher in both 1989 and 1990, but the difference in pass rates between the two examinations narrowed in 1990. (4) The percentage of repeaters taking the NBME was high in 1989 and declined in 1990. (5) The number of previous takes among repeaters was higher for the NBME than for the FMGEMS in 1989 and became equal in 1990. CONCLUSIONS: Some students probably opted to take the NBME in 1989 in the belief that it might be easier than the FMGEMS, resulting in lower pass rates for the NBME. The NBME pass rates rose in 1990 after the differential pass rates had become public. PMID- 8431238 TI - Effects of examinee gender, standardized-patient gender, and their interaction on standardized patients' ratings of examinees' interpersonal and communication skills. AB - PURPOSE: To assess the effects of examinee gender, standardized-patient (SP) gender, and, in particular, their interaction on ratings made by SPs of examinees' interpersonal and communication skills in a performance-based examination of clinical competence. METHOD: The examination was administered to four classes of senior medical students (about 70 per class) at Southern Illinois University School of Medicine, 1988-1991. The skill dimensions tested were clarity of communication, thoroughness of explanation, professional manner, personal manner, and overall patient satisfaction. Split-plot analyses of variance were used. RESULTS: There was no interaction of examinee gender and SP gender for any of the five rating scales. There was no main effect of examinee gender for four of the five scales; however, for personal manner, women students were rated slightly higher than men students. There was a main effect of SP gender, but the effect was not consistent from rating scale to rating scale or from class to class. Nevertheless, differences in ratings given by men and women SPs should not be of psychometric concern, since the ratings of men and women examinees are necessarily affected alike. CONCLUSIONS: Except for the women examinee's higher performance in personal manner, the men and women examinees generally performed equally well with respect to interpersonal and communication skills, and they performed equally well regardless of the gender of the SP. PMID- 8431239 TI - Changes in the patterns of specialties selected by high and low academic performers before and after 1980. AB - BACKGROUND: The goal of this study was to examine whether recently observed changes in the distribution of medical school graduates' choices are linked to level of academic achievement, graduation year, or both. METHOD: The authors studied the specialty selections made by two groups of graduates of the University of Kentucky College of Medicine: 319 who were elected to Alpha Omega Alpha and 276 who ranked academically in the bottom 10% of their classes. They also divided the groups into two time frames: 1964-1979 and 1980-1991. Two-way factorial analyses of variance compared the distributions of specialty selections according to time frame and to academic group. RESULTS: Significantly higher percentages of students in the low-achievement group selected primary care specialties (F = 14.76, p < .001), and this difference between the academic groups increased in recent years: 67% versus 41% in 1980-1991 compared with 53% versus 46% in 1964-1979. CONCLUSIONS: The specialty options most readily available to academically low-achieving medical school graduates are narrowing. Low achievers may be funneled into primary care simply because they cannot compete for other specialties. The authors recommend that: (1) recruitment and selection into primary care specialties should be made only after each candidate has been assessed over a broad range of cognitive and noncognitive factors and (2) academically low-ranking graduates should not end up in primary care specialties simply because no other specialty options are available to them. PMID- 8431240 TI - Selection of anesthesiology residents. AB - BACKGROUND: CARCS (computer-assisted resident candidate selection) is a database application developed in 1983 at the Department of Anesthesiology of the Medical University of South Carolina to deal with the greatly increased quantity of applicant information. This article relates a representative sample of CARCS data to the process of selecting residents in general. METHOD AND RESULTS: CARCS files were analyzed for 1985-86, 1986-87, 1990-91, and 1991-92, and data for each year were derived as simple averages and percentages for two groups: (1) the entire pool of residency applicants (approximately 200 per year) and (2) the eight residency candidates per year who actually matched with the program through the National Resident Matching Program, Analyses showed that the standardized test scores, grades, and class ranks of the matched candidates were not significantly higher than those of the applicants; however, the matched candidates' scores for letters of reference and for interviews were consistently higher than those for the applicant pool. CONCLUSIONS: The results support the view of medical educators that the traditional academic criteria are not sufficiently predictive of clinical performance or interpersonal skills. Research relating residents' performances to personality, learning style, and other neuropsychological factors may provide needed alternatives to knowledge testing by developing combined cognitive-noncognitive profiles. The anesthesiology clerkship experience is now almost universal among applicants and could be structured to provide pertinent information about potential residents through direct observation as well as behavioral testing. PMID- 8431241 TI - Changes in residents' self-assessed competences during a two-year family practice program. AB - PURPOSE: To compare changes in self-assessed clinical confidence over a two-year residency between two groups of family practice residents, one starting in a family practice center and the other starting in a hospital. METHOD: All 44 entering residents at the University of Western Ontario in either 1984 or 1985 were eligible. Forty-two participated at baseline, and 24 (57%) provided completed responses after two years. Confidence regarding 177 topics in 19 general topic areas was assessed using self-completed questionnaires administered at baseline and after six, 12, and 24 months. The residents rotated every six months between sites, with approximately half starting in each site. Nonrandom assignment to starting site included consideration of the residents' stated preferences; hence self-selection bias was possible. Mean differences were evaluated using t-tests, and trends over time were assessed using repeated measures analysis of variance. RESULTS: There was no difference between the groups' grand means at any time. In the 19 areas, five statistically significant differences were seen, four at six months and one at 12 months; four involved greater confidence by the center-start group. No difference was seen after two years, and both groups displayed substantial increases in confidence over two years. CONCLUSIONS: The few significant differences in confidence between the two groups suggest that their training might have been deficient if it had omitted one of the settings. However, because these differences had disappeared after the groups had each experienced 12 months in each setting, the initial site of training appears not to affect learning. PMID- 8431242 TI - Physicians' productivity and teaching responsibilities. AB - BACKGROUND: There is considerable concern about the impact of teaching responsibilities on physicians' productivity. Previous research employing independent sample designs has suggested that physicians who teach medical students are less productive then their nonteaching counterparts. METHOD: This study examined the productivity of 15 family practice faculty and third-year resident physicians practicing in the Family Medical Center of the University of Kentucky College of Medicine; in addition to the care of patients, the physicians were assigned to teach third-year medical students participating in an ambulatory primary care clerkship. The productivity of each physician (i.e., number of patients seen per half day) was measured during a four-month period in the spring of 1991. The physicians' levels of productivity with and without medical students were compared through the use of a paired-sample design. RESULTS: No significant difference in productivity levels was observed. CONCLUSION: Ambulatory-care teaching responsibilities may not diminish physicians' productivity in academic teaching practices. PMID- 8431243 TI - Comparison of patients' and their resident physicians' responses regarding smoking-cessation interventions. AB - PURPOSE: To investigate (1) the extent of agreement between what resident physicians and their patients report as having occurred in physician-delivered smoking interventions and (2) the ability of residents to effectively transmit information concerning smoking interventions to their patients. METHODS: A total of 263 patients and 91 residents in internal medicine or family practice completed paper-and-pencil exit interviews after a regularly scheduled clinic appointment between 1986 and 1988 at the University of Massachusetts Medical School; the residents had been trained to deliver counseling interventions. The kappa statistic was used as an index of chance-corrected agreement between the patients' and residents' responses. RESULTS: Agreement was substantial regarding whether a specific plan for the patient to stop or reduce smoking was agreed upon, whether written materials on how to quit smoking were provided, and whether nicotine-containing chewing gum was prescribed. CONCLUSIONS: There was positive agreement between the patients and their resident physicians concerning the residents' delivery of quit-smoking messages and the provision of written materials to assist in stopping. Programs must continue to be designed, for residents and for more senior physicians, so that physicians can be encouraged to incorporate smoking interventions into their practice activities. PMID- 8431244 TI - Consulting-skills training to improve medical students' diagnostic efficiency. PMID- 8431245 TI - First-year medical students' opinions and projected practice behaviors regarding abortion. PMID- 8431246 TI - Usefulness of a data-collection form in learning physical diagnosis. PMID- 8431247 TI - Evaluating the competence of physicians in practice: from peer review to performance assessment. AB - Evaluation of physician competence has traditionally been defined by the medical profession largely through standardized tests and board certifying examinations. However, a level of physician evaluation that takes place outside academic medical centers and certifying boards is rapidly developing. This article describes three programs for such physician evaluation: (1) the program of US Healthcare, a national managed health care company; (2) the DEMPAQ--Developing and Evaluating Methods to Promote Ambulatory Care Quality--project, a joint research effort between Harvard University (Cambridge, Massachusetts) and the State of Maryland's (and District of Columbia's) Peer Review Organization (PRO); and (3) a project initiated by the American College of Physicians (ACP) in Philadelphia, Pennsylvania, to assess both medical competence and technical performance in the hospital setting. The authors argue for the need to inform physicians-in-training about the types of evaluation to which they will be subjected over the courses of their careers. In order to further this goal, the authors advocate increased collaboration between leaders in the academic setting and those spearheading these new programs for assessment of physician performance. PMID- 8431248 TI - Assessment during postgraduate training. AB - The author reviews the traditional process of assessing both undergraduates in medical school and physicians in postgraduate training, contending that this traditional, and still dominant, process is inadequate because of its limitations. It focuses narrowly on end-point evaluation, using predominantly multiple-choice questions, rather than on identifying deficiencies during the training period so that trainees are able to correct these deficiencies before their end-point evaluations. An example of a more valid process of assessment is the set of tests employed by the Royal Australian College of General Practitioners to assess the skills of family practice physicians, by using behavioral ratings. The author concludes that where such tests are used, there may be some difficulty in comparing the performances of undergraduates with those of practicing physicians, in view of the different behaviors being assessed. In any follow-up studies of graduates, attention should be paid to the reliability and validity of the assessment procedures, particularly because differences in the assessment tools may account for some discrepancies between training programs. PMID- 8431249 TI - Relevance of "irrelevant" facts in medical education: the value of basic science teaching for later medical practice. AB - The relationship between performance measures in medical school and in practice is addressed in this article in terms of the relevance to the physician's practice of the facts learned in medical school. It is argued that despite the fact that "relevance" and "irrelevance" are relative terms, medical education should place emphasis on the "core" curriculum on the assumption that core materials have important applications in practice and therefore are more relevant when investigating relationships between performances in medical school and after graduation. Although some of the "relevant" facts may seem "irrelevant" to medical students, medical school faculty and members of curriculum committees should be committed to include relevant facts in the core curriculum based on their professional hindsight and feedback from practicing physicians. PMID- 8431250 TI - Perspectives in assessment. PMID- 8431251 TI - The empirical association between student and resident physician performances. AB - To further the understanding of the relationship between performances in a combined baccalaureate-MD degree program and in residency, the authors subjected their database of 298 study participants from the 1980-1983 entering classes of the University of Missouri-Kansas City School of Medicine to factor analysis and then to distribution-free statistical analyses. Distinct factors were identified among the performance measures from the combined-degree program; only one factor was identified among the measures of residency performance. Analysis of the relationship of performances in the combined-degree program and in residency indicated that almost half of the participants were in the same performance categories as students and as residents. The strongest association emerged between a clinical performance factor derived from performances in the combined degree program and the residency clinical performance factor. However, the knowledge factor derived from performance measures in the combined-degree program was also associated with residency clinical performance. The associations were statistically significant but of limited strength; thus the present results resemble those of other investigators, despite the fact that they are based on distribution-free statistics and on purportedly cleaner and more homogeneous measures of performance. Various technical reasons may have caused this lack of strength, but it is also possible that empirical relationships between undergraduate and postgraduate performances are inherently limited because the performances expected of residents may not be mere extensions of those expected of medical students. PMID- 8431252 TI - Clinical performance-based test sensitivity and specificity in predicting first year residency performance. AB - To assess the use of a standardized-patient-based postclerkship examination (PCX) to predict students' performances in their first year of residency, the authors used data from 202 students of the classes of 1987, 1988, and 1990 at the Southern Illinois University School of Medicine. The PCX was found to be more sensitive than specific in that it identified more correctly those students who received high ratings in their first year of residency than those who received low ratings. Consequently, while the rate of false negatives was low across the three classes, the rate of false positives was relatively high. Analyses of the supervisors' written comments on residents' performances indicated that more than half of the false positives and false negatives resulted mostly from problems found with the supervisors' ratings, rather than from the inaccuracy of the PCX in predicting students' residency performances. The supervisors' ratings did not always match their written comments and did not always represent pure assessments of the residents' cognitive performances. Finally, because of the large number of missing residency performance ratings among the graduates who had performed unsatisfactorily on the PCX, it is expected that the sensitivity of the PCX may be overestimated and its specificity underestimated. Overall, the results suggest that the standardized-patient-based PCX is a useful indicator of students' readiness for and performance in residency. PMID- 8431253 TI - Relationships of interns' performances to their self-assessments of their preparedness for internship and to their academic performances in medical school. AB - This study addressed the questions of whether medical students' cumulative grade point averages (GPAs) correlate with the performance assessments (overall and in specific areas of competency) that they receive as interns from their internship program directors, and whether the students' self-assessments of preparedness for internship correlate with their internship directors' overall assessments. A questionnaire to assess interns' competencies was developed and sent to the directors of the internship programs of the 283 1990 and 1991 graduates of the Medical College of Georgia School of Medicine who consented to participate in the study (82% of the graduates). Eighty percent of the program directors responded. A similar questionnaire was sent to all 342 of the 1990 and 1991 graduates; 38% provided self-assessments of their competencies and also stated their views on how well prepared they were for their internships. Considering the classes as a group, the mean ratings of the interns' overall competencies by the program directors ranged from 3.7 to 4.3 on a five-point Likert scale (1, unsatisfactory, to 5, outstanding), whereas the interns' ratings of how well they were prepared for their internships (that is, their sense of overall competency) were somewhat lower, ranging from 3.4 to 4.0. The correlations of GPAs with the specific areas of competencies ranged from .28 to .51. The correlation between the mean ratings of the program directors and the mean self-ratings of the interns was .58. The data support the conclusions that medical school academic performance relates significantly to performance in internship and that interns do not rate themselves as highly as their program directors do. PMID- 8431254 TI - Validity of NBME Part I and Part II scores for selection of residents in orthopaedic surgery, dermatology, and preventive medicine. AB - This study investigated the relationship between the National Board of Medical Examiners (NBME) Part I and Part II examination scores and subsequent performances on the 1991 certification examinations of the American Boards of Orthopaedic Surgery (ABOS), Dermatology (ABD), and Preventive Medicine (ABPM). There were significant correlations between scores on all specialty board examinations and all NBME scores, with higher correlations for subscores more closely related to specialty content. Both NBME Part I and NBME Part II were useful predictors; however, the relationships with NBME Part II were generally stronger. Strong relationships were observed between specialty board pass-fail outcomes and NBME scores: examinees whose NBME scores were below 400 were at much greater risk for failing their specialty board examinations. PMID- 8431255 TI - Lifelong learning of physicians: contributions of different educational phases to practice performance. AB - This pilot study was designed to find out where and when in their education physicians thought they had acquired the competencies they used in their daily practices five years after completion of their formal training. Specifically, the study sought physicians' views about the relative contributions of seven major phases of medical education (i.e., preclinical, clinical, "practice phases 1 and 2," specialty training, formal continuing education, and independent learning) to their practice performances. In 1991, the authors distributed a questionnaire to 330 physicians participating in a continuing medical education course in Germany, asking them about the relative contributions of these educational phases to their practice performances. A total of 141 (43%) returned questionnaires, of which 114 were suitable for evaluation. Specialty education was believed to have contributed most to the physicians' daily practices, with a median contribution of 20%. Practice-based independent learning, in which 38% participated in groups, contributed, with a median of 18%, and was superior to formal continuing education, with a median of 5%, and to university education, 15%. The frequency distribution of the percentages allotted to the seven phases showed great variation. Thirty-four respondents stated that they had not gained appreciably from preclinical education or formal continuing education but that the other five phases had contributed 50% to 90% of the knowledge and skills they used in their practices. PMID- 8431256 TI - Examination of nonresponse bias in a major residency follow-up study. AB - Nonresponse bias is a potential problem for follow-up studies that track medical school graduates into their residencies. There are two main types of nonresponse: when residents' supervisors do not complete the study evaluation forms and when medical students refuse permission to allow follow-up evaluations during their residencies. The present study discloses the biases that each of these types of nonresponse produced on a set of standard measures of 508 residents from eight 1980s medical school classes at Southern Illinois University. The standard measures (e.g., MCAT scores, grade-point averages, NBME scores) were collected when the residents were medical students. The findings clearly indicate that the scores of the medical students who granted permission for follow-up evaluations had significantly larger means than did the scores on the same measures of those students not granting permission, clearly a source of nonresponse bias. On the other hand, no significant difference in scores (thus negligible bias) was found in cases where supervisors did not complete forms. The authors offer suggestions for medical school policies based on these findings. PMID- 8431257 TI - Measuring and predicting the performances of practicing physicians: an overview of two decades of research at the University of Utah. AB - This paper presents the major findings of research carried out by a team of investigators at the University of Utah School of Medicine in the 1960s and 1970s (1) to better understand the multidimensional and complex aspects of practicing physicians' performances, and (2) to investigate relationships between assessments of students in medical school and physicians' performances. The major research began in the 1960s, and data were assembled from a variety of sources to identify factors of physicians' performances. The original study sampled 507 practicing physicians, classified into four highly diverse and representative groups. The team also investigated to what degree these physicians' medical school performances (measured by grades) were predictors of their practice performances. Factor analysis of the data on the physicians' performances resulted in the identification of 25 to 29 factors within each of the four groups. A representative profile of the performances of each physician studied showed how well the physician performed on each of the factors appropriate to his or her specialty and background. Correlation analysis demonstrated that these physicians' performances in medical school, as measured by grade-point averages (GPAs), were almost completely independent of their later performances in their practices, a disturbing finding and one that the team maintained cannot be dismissed by arguments of "restriction of range." In the teams' later studies, 61 measures of physicians' performances were correlated to medical school GPAs in the two basic science years and the two clinical science years. No association beyond chance was observed, and nonsignificant relationships held up regardless of the physicians' specialties or years of experience.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431259 TI - What have we learned, and where do we go from here? PMID- 8431258 TI - Is the glass half full or half empty? A reexamination of the associations between assessment measures during medical school and clinical competence after graduation. AB - The purpose of this study was to investigate the associations between performances during medical school and in the first year of residency. It was hypothesized that the strength of such associations is a function of several variables, including similarities of the measured concepts, the formats of the assessments, the time interval between the assessments, performance levels, and specialty areas. The total sample consisted of 2,368 graduates of Jefferson Medical College between 1980 through 1990. The performance measures in medical school were grades on objective examinations in basic and clinical sciences, global ratings of clinical competence in junior core clerkships, and scores on the Part I and Part II examinations of the National Board of Medical Examiners (NBME). The postgraduate performance measures were scores on the Part III NBME examination, postgraduate competence ratings, and board certification. The ratings of postgraduate clinical competence (available for 73% of graduates) were made by residency directors at the end of the first year of residency in the areas of data-gathering and processing skills, interpersonal skills and attitudes, and socioeconomic aspects of patient care. Results supported the research hypotheses. It was found that the associations varied for different measures, at different levels of performance, and in different specialties. The authors conclude that the glass is "half full" regarding the associations between assessment measures before and after graduation from medical school. PMID- 8431260 TI - A case of mistaken identity: signal and noise in connecting performance assessments before and after graduation from medical school. AB - The authors examine the assumption that there is continuity from one level of training to another in structured and purposeful professional education. Thus, more advanced levels of training are built upon the foundations laid in the preceding levels. While the connection between performance before and performance after graduation from medical school is theoretically rational, such a connection has not been well documented in empirical studies. The issue has been debated but has not been settled because relevant findings are inconsistent. It is argued that these inconsistencies can stem from contaminating factors and the conceptual and methodologic limitations of empirical studies. Such limitations are described in terms of "noise" that obscures the maximal value of a true relationship (the "signal"). Contaminating factors such as the time interval between testings; institutional factors; specialty choices; conceptual dissimilarities between performance measures in medical school and in practice; methodologic limitations such as the shapes of rating distributions, nonlinearity, heteroscedasticity, restriction of range, multicollinearity, voluntary participation, psychometrics of assessment instruments and differing methods of assessments; and a lack of assessments of personal qualities can produce "noise" that inhibits the strength of the "signal." While suggesting solutions for extricating some of the tangled web of methodologic and conceptual issues, the authors feel that solutions do not exist for all of the problems. They conclude that researchers should be aware of the limitations if they are to avoid underestimating the "signal," which may fade because of background "noise." PMID- 8431261 TI - Diagnosis of carpal tunnel syndrome. The gold standard. PMID- 8431262 TI - Anodal block V anodal stimulation. Fact or fiction. AB - Anodal block and stimulation are poorly documented electrophysiologic phenomenon. Median and superficial radial nerves are examined in a prospective study to explore the significance of anodal block in routine nerve conduction studies. In addition, the anode's ability to stimulate the peripheral nervous system is evaluated. A monopolar stimulation technique is employed to achieve pure anode generated responses. Additionally, a similar monopolar cathode stimulation technique is utilized and found to be equivalent to the traditional bipolar cathode stimulation. Based on the findings in this investigation, anodal block does not appear to occur during routine nerve conduction studies; however, transposition of the anode and cathode is clinically significant because the increased distance between the cathode and recording electrode results in predictably prolonged latencies. With higher levels of stimulus intensity, sensory, motor and F wave responses are generated by anodal stimulation in all cases. The actual mechanism of anodal stimulation remains uncertain and requires further study. Predicated on the results of this investigation, it appears that anodal block is an unlikely occurrence during routine electrodiagnostic medicine evaluations. PMID- 8431263 TI - Silent periods after electromagnetic stimulation of the motor cortex. AB - Electromagnetic stimulation has been used to excite tracts in the human motor cortex, but little has been done to study inhibitory effects. In three normal subjects we have noted that an electromagnetic stimulation applied to the motor cortex during maximum voluntary contraction produces silent periods lasting up to 300 ms in the contralateral abductor pollicis brevis. Duration of the silent period is directly proportional to the intensity of the stimulus. Abductor hallucis has similar silent periods lasting 150 to 200 ms, although proximal upper and lower limb muscles have shorter silent periods. F and H waves are easily elicited during this silent period suggesting that the alpha motoneuron is still excitable. This silent period may result, at least in part, from a synchronous volley of inhibitory postsynaptic potentials induced by the electromagnetic stimulator at the cortical level. This technique may prove useful in further delineating cortical inhibitory function. PMID- 8431264 TI - Transcutaneous oxygen pressure. An effective measure for prosthesis fitting on below-knee amputations. AB - After amputation for arterial occlusive disease of the lower limbs, healing and local adaptation to a prosthesis depend on the oxygen ratio in the tissue. Transcutaneous oxygen tension (TcPO2) is a noninvasive microcirculatory exploration. Forty six below-knee stumps were selected without any prosthetic problem excepting vascular, with a follow-up mean duration of 23 months. They were classified into different prosthetic categories. The first was the worst because it required further amputation on the thigh and the fourth the best, which displayed complete adaptation to a socket contact. These groups were related to their TcPO2 values on the anterior and exterior face of the stumps in both reclined and seated positions. It seems that it is impossible to achieve healing when the TcPO2 value is lower than 15 mm Hg in lying position. However, healing is possible above 20 mm Hg but socket contact is not possible when TcPO2 values are under 40 mm Hg. When TcPO2 values are above 40 mm Hg, a good prosthesis fitting is possible when no problems are encountered other than vascular ones. PMID- 8431265 TI - The Uniform Data System for Medical Rehabilitation report of first admissions for 1991. PMID- 8431266 TI - Sacral reflex latencies in tethered cord syndrome. AB - We performed electrophysiologic evaluation in three adult patients with diagnosis of tethered cord syndrome confirmed by magnetic resonance imaging. In addition to lower motor neuron lesion signs in the lumbar and sacral myomeres we noticed shortened latencies for the H and bulbocavernosus reflexes. H reflex latencies ranged from 23.3 to 26.0 ms; bulbocavernosus reflex latencies ranged from 18.2 to 20.2 ms. The low location of the conus medullaris accounts for the shortening of the monosynaptic H reflex and for a part of the shortening of the polysynaptic bulbocavernosus reflex, anoxia of the conus being probably another important factor. In the absence of previous description of alternative pathology accountable for such a shortening, our observations suggest that shortened sacral reflex latencies might be specific of the tethered cord syndrome. PMID- 8431268 TI - Recommended guidelines for admission of candidates with disabilities to medical school. Developed by the Association of Academic Physiatrists. PMID- 8431267 TI - Hamstring tightness and Scheuermann's disease. Commentary. PMID- 8431269 TI - The role of ethics in rehabilitation medicine. Introduction to a series. PMID- 8431270 TI - Medical economics of PM&R. V. Surviving the complexities of academic medical centers. AB - The mission statements of academic medical centers call on them to accomplish many goals. This often leads to conflicting choices when selecting activities and establishing policies. When individual faculty members are expected to divide work time to meet research, teaching and clinical needs, careful planning and disciplined decisions of action are necessary to avoid a sense of ambiguity and frustration. PMID- 8431271 TI - Scrotal temperature in spinal cord injury. AB - Twenty-five spinal cord-injured (SCI) males and 25 normal volunteers were studied for their scrotal and thigh temperatures by using contact liquid crystal thermography. The initial temperature was recorded after transfer and disrobing which took about 2 minutes. Later temperature was recorded 10 minutes after exposing the genitalia to room air (20-22 degrees C). The initial scrotal and thigh temperatures of SCI subjects were significantly higher than those of normal volunteers (32.8 +/- 0.8 degrees C v 31.6 +/- 0.4 degrees C; 32.9 +/- 0.8 degrees C v 31.7 +/- 0.4 degrees C, respectively, P < 0.001), although their rectal temperatures were not different. The scrotal and thigh hyperthermia of SCI subjects disappeared after 10 minutes of exposure to room air. There was no significant difference between scrotal and thigh temperatures in either the SCI subjects or the normal volunteers in the later temperature reading. Sitting in a wheelchair for 2 hours results in an increase of average 0.8 degrees C of scrotal and thigh temperature in five normal volunteers. Our study suggests that scrotal hyperthermia of SCI subjects is mainly the result of local factors such as a prolonged sitting position, adduction of the thighs, the cushion's insulating effect and infrequent movement of the buttocks. Adequate ventilation of the scrotal area can overcome the impaired scrotal heat dissipation of SCI subjects. Liquid crystal thermography is a useful, noninvasive method for detecting hyperthermia in SCI subjects. PMID- 8431272 TI - Comparison of a formamide-based stripping method with a hot SDS method. PMID- 8431273 TI - A one-hour procedure for the preparation of genomic DNA from frozen tissues. PMID- 8431274 TI - A more robust, rapid alkaline denaturation sequencing method. PMID- 8431275 TI - A rapid procedure for isolation of RNA-free genomic DNA from mammalian cells. PMID- 8431276 TI - A method for obtaining high-quality sequences from the non-biotinylated, free ssDNA remaining after solid-phase sequencing. PMID- 8431277 TI - Use of a support film in Southern hybridizations employing dried agarose gels. PMID- 8431278 TI - Reagent-saving method for incubation and washing of blotting membranes. PMID- 8431279 TI - Use of an autoclavable bottletop dispenser to rapidly pour agar plates. PMID- 8431280 TI - A simple method for isolation of DNA from blood clots suited for use in PCR. AB - We describe a rapid, simple and inexpensive method for the isolation of DNA from blood clots suited for use in PCR. Our method is based on the lysing and nuclease inactivating properties of guanidine thiocyanate together with the nucleic acid binding properties of silica particles. Isolated DNA can be used for in vitro amplification as shown for a retinoblastoma gene PCR system. PMID- 8431281 TI - Effects of blood storage time and temperature on DNA yield and quality. AB - Whole blood is a common source of DNA, especially for genotype diagnostic services. Many laboratories now receive blood samples by mail and/or store blood samples prior to DNA extraction. Therefore, the effects of storage time (number of days from blood collection to DNA extraction) and temperature on DNA yield and quality are important. We compared DNA yield and quality from bovine blood samples exposed to one of sixteen treatment combinations of storage time (3, 7, 14 or 28 days) and temperature (-20 degrees, 4 degrees, 23 degrees or 37 degrees C) to the results obtained when DNA was extracted within 4 h of collection. The highest mean DNA yields, relative to the control samples, were obtained from blood stored at 4 degrees C. Blood stored at 37 degrees C for > or = 3 days or 23 degrees C for > or = 7 days yielded less (P < .05) DNA, compared with blood stored at 4 degrees or -20 degrees C for up to 28 days. DNA was not recovered from three of the samples stored at 23 degrees C and five of the samples stored at 37 degrees C. The genomic DNA obtained was of high molecular weight and suitable for restriction enzyme digestion and PCR amplification, regardless of the treatment. PMID- 8431282 TI - A rapid and inexpensive procedure for separation of high molecular weight DNA. AB - A pulse field gel electrophoresis procedure suitable for a variety of uses is described. The protocol has a run time of four hours. It was developed using field inversion technology and conventional gel boxes and is run at room temperature. This procedure provides a quick and inexpensive alternative for separation of high molecular weight DNA. PMID- 8431283 TI - Biotin-containing protein as a cause of false positive clones in gene probing with streptavidin/biotin. AB - Using a streptavidin/biotin labeling technique, we unintentionally cloned a gene encoding a biotin carboxyl carrier protein, a subunit of biotin-dependent enzymes, from a genomic library of Streptococcus mutans strain UT-041. In colony lifts, the clone reacted positively to the streptavidin-containing detection system but could not be detected in Southern blot analysis. The amino acid sequence of the gene product, deduced from its nucleotide sequence, demonstrated all the features common to biotin carboxyl carrier proteins from other bacteria, indicating that the biotin carboxyl carrier protein in the clone had produced a "false-positive" (DNA probe-independent) reaction by binding to the streptovidin. To circumvent this problem with the detection system in gene probing in the future, we recommend that all positive clones be screened by direct incubation with streptavidin-alkaline phosphatase (SA-AP) in the absence of biotin-labeled probe DNA. Clones binding to SA-AP would be considered false positives. PMID- 8431284 TI - Artifactual variation in randomly amplified polymorphic DNA banding patterns. AB - Randomly amplified polymorphic DNA (RAPD) and arbitrarily primed PCR (AP-PCR) represent novel DNA polymorphism assays that involve the amplification of random DNA segments using PCR and oligonucleotide primers of arbitrary sequence. Products defining the polymorphisms exhibit Mendelian inheritance and thus possess tremendous potential utility as genetic markers in a diverse array of scientific disciplines. Amplification profiles for specific oligonucleotide primers are highly dependent on the specific conditions of the reaction; banding patterns may thus vary extensively because of inconsistencies in a number of reaction parameters. Artifactual variation represents a potential problem in surveys of genetic variation in natural populations and must be discriminated from true polymorphism for the applications of RAPD to be both accurate and reliable. PMID- 8431285 TI - Direct sequencing of PCR products using unlabeled primers. AB - An improved protocol is described for using lambda exonuclease to directly sequence PCR products. It is important not to execute PCR cycles beyond the plateau of amplification. The asymmetric PCR and double-stranded DNA sequencing by a snap-cooling procedure were also performed using the same DNA samples and primers. The improved method was the most reliable and produced the best results. PMID- 8431287 TI - Transformation of Helicobacter pylori by electroporation. AB - A highly efficient method of introducing DNA into an important human pathogen is reported here. Electroporation-mediated transformation of a laboratory-passaged isolate of Helicobacter pylori was successfully used to establish genetic mutants at a transformation frequency of > 10(5)/micrograms DNA. This method should be widely applicable to all isolates of H. pylori and may eliminate the variability reported when natural transformation was used on fresh clinical isolates. PMID- 8431286 TI - SP6 RNA polymerase containing vaccinia virus for rapid expression of cloned genes in tissue culture. AB - A hybrid transient expression system, in which tissue culture cells are infected with a recombinant vaccinia virus encoding bacteriophage DNA-dependent RNA polymerase and transfected with a plasmid containing a cloned gene behind the bacteriophage promoter, allows rapid high-level expression in nearly 100% of the cells. In order to extend this system to clones from libraries containing SP6 promoters, a new vaccinia virus was constructed encoding bacteriophage SP6 RNA polymerase. PMID- 8431288 TI - An autosampler for fermentation. AB - The operation of an autosampler, constructed from a peristatic pump, an interval timer and a fraction collector, for the removal of whole broth fermentation samples is described. The autosampler repetitively removes samples of user determined size at repetitive time intervals. The sampler is intended for use with low containment fermentations. A comparison of the autosampler and the manual sampler of a fermenter showed good correlation of substrate consumption rates when changes were sizeable and superior results were obtained with the autosampler when the changes were subtle during a typical diauxic fermentation of Azotobacter vinelandii. PMID- 8431289 TI - Substitution of DMSO for DMF as a solvent for X-gal. PMID- 8431290 TI - FoLT PCR: a simple PCR protocol for amplifying DNA directly from whole blood. AB - FoLT (formamide low temperature) PCR is a protocol for amplifying DNA directly from whole blood without any preparative steps. Up to 10% (vol/vol) whole blood can be added directly into the tube containing the PCR mixture. There is no need for transfers, centrifugations, pre-boiling or any preparative step. It involves the use of formamide (18% vol/vol) as well as reduced incubation temperatures (cycles of 85 degrees, 40 degrees, 60 degrees C). The type of anticoagulant used was critical: sodium heparin or EDTA being superior to lithium or fluoride heparin. Our studies indicate that FoLT PCR probably works by reducing the amount of protein coagulation and allowing more DNA template to be accessible for amplification. The sensitivity of FoLT PCR is such that a single copy gene from 5.5 nucleated cells in 1 microliter of whole blood can be detected. PMID- 8431291 TI - A vector for facile PCR product cloning and modification generating any desired 4 base 5' overhang: pRPM. AB - A pair of plasmids were developed for cloning PCR products in order to facilitate the preparation of products with 5' overhangs consisting of any desired 4 nucleotide sequence. These vectors allow DNA to be cloned into a unique restriction site by blunt-end ligation or by AT-cloning. The cloned DNA is subsequently excised using class IIS restriction enzyme sites flanking the insert yielding a fragment that is entirely free of vector sequences. These enzymes recognize sequences in the vector but "reach-over" the junction to cut within the insert thereby generating a 4-base 5' overhang sequence determined by the 5' sequences in the insert. Thus, in cases where the insert was originally generated by PCR, the overhangs are specified by the primer. More generally, these vectors offer a unique capability for the reversible cloning of any blunt DNA fragment because excision and fill-in reactions precisely regenerate the original blunt fragment regardless of its sequence. These "reach-over" product modification vectors represent general and flexible tools for the generation of fragments for use in engineering DNA constructs. PMID- 8431292 TI - Selection of an active single chain Fv antibody from a protein linker library prepared by enzymatic inverse PCR. AB - Enzymatic inverse PCR mutagenesis was developed as a simple and reliable method for the construction of large libraries of site-directed mutants. Enzymatic inverse PCR library mutagenesis uses a single PCR fragment and is restriction site independent. The usefulness of the technique was demonstrated by the design of a single chain linker for an antibody Fv fragment without computer modeling. The Fv fragment of an antibody specific for a metal chelate was expressed in active form in the periplasm of E. coli. The light and the heavy chains of the Fv are expressed as a bicistronic mRNA. Enzymatic inverse PCR mutagenesis was used to construct a library of 3 x 10(5) Fv mutants, in which the C-terminus of the light chain was connected to the N-terminus of the heavy chain by a 15-amino acid peptide linker of variable composition. After plating, active mutant colonies were identified by screening colony filter lifts with a radiolabeled hapten, N' (2-hydroxyethyl)-p-thioureidobenzyl EDTA. About 0.2% of the mutants were positive, and a selected sFv clone was shown to have the same affinity as the Fv (9 x 10(9)) and was similar to the whole antibody (11 x 10(9)). This example compares favorably with both of the other approaches to constructing sFv's; namely, molecularly modeled linkers as well as universal linkers, which have often yielded significantly lower affinities than whole antibodies or Fabs. The enzymatic inverse PCR library mutagenesis approach is simple and reliable and can be used to obtain linkers for the great majority of antibodies for which no structural data are available. More generally, it can be used to modify DNA coding for any structural protein or regulatory element. PMID- 8431293 TI - Fractionation of small tryptic phosphopeptides by alkaline PAGE followed by amino acid sequencing. AB - A novel two-step approach for localizing the site(s) of phosphorylation within intact proteins is described. Phosphorylated (32P-labeled) tryptic peptides are first resolved in a high-percentage polyacrylamide gel that has been optimized for the enrichment and separation of small, negatively charged peptides. Then the resolved peptides are located by autoradiography, excised, eluted and immobilized on a positively charged membrane, Immobilon -N, where they can be sequenced directly. The methods have been developed using a small, basic phosphoprotein (histone H1 from Tetrahymena); however, the approach is probably applicable to a wide variety of phosphoproteins. PMID- 8431294 TI - Rapid purification of recombinant baculovirus using fluorescence-activated cell sorting. AB - Expression of foreign proteins in the baculovirus-insect cell expression system has been limited by difficulties in rapid identification and purification of recombinant virus. Although the process of identifying recombinant virus has been greatly facilitated by the introduction of vectors that lead to insect cell co expression of beta-galactosidase with foreign genes of interest, isolation of pure recombinant virus using plaque purification may still take several weeks to months to accomplish. Using a fluorescent beta-galactosidase substrate, we have established that insect cells harboring recombinant virus can be rapidly isolated using fluorescence-activated cell sorting. Pure recombinant virus can then be readily obtained using this cellular fraction, with a pure viral culture generally obtained within 2-3 weeks of insect cell transfection. PMID- 8431295 TI - The GenePrint Light method for Southern transfer and chemiluminescent detection of human genomic DNA. AB - A simple, fast and sensitive method to perform Southern transfer and hybridization with nonradioactive detection of genetic loci is described. With a 10-ng sample of human genomic DNA, alleles of the D2S44 locus can be detected within 7 h of completing gel electrophoresis. PMID- 8431296 TI - Progress in cardio-thoracic surgery: freedom or control and regulations? Presidential address. PMID- 8431297 TI - The role of ultrasound assisted thoracoscopy in the diagnosis of pleural disease. Clinical experience in 687 cases. AB - Ultrasonic examination is an established method used to differentiate between solid and liquid structures in the pleural space. It can estimate the volume of a pleural effusion and demonstrate whether the effusion is associated with loculations or adhesions. It is complementary to thoracoscopy. In the diagnosis of pleural disease ultrasonic-assisted thoracoscopy should only be used when the less invasive methods of diagnosis such as pleural aspiration for cytological, bacteriological and chemical examinations and needle biopsy of the pleura have not yielded a diagnosis. Although thoracoscopy is a relatively invasive procedure, it has the advantages of speed and accuracy in the diagnosis of pleural disease. This procedure is not widely used as it requires specialized instruments and equipment and may be time-consuming. The latter disadvantage may be minimized by the use of prior pleural sonography. The ultrasonic examination will indicate the optimal point of entry of the thoracoscopy to avoid adhesions. In order to evaluate feasibility, complications and clinical results in ultrasonic-assisted thoracoscopy, we investigated 687 patients with pleural diseases from 1987 to 1990. As prior induction of a pneumothorax under X-ray control was not necessary, the 20-30 min required for this procedure was saved in all patients. Very few complications were attributable to ultrasonic-assisted thoracoscopy as it could normally be performed under local anesthesia. A macroscopic diagnosis was made in 80% of malignant diseases and 77% of inflammatory diseases in our total of 687 thoracoscopies. The diagnosis of a malignant pleural effusion was confirmed histologically and cytologically in 95% of those 190 patients in whom it was present.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431298 TI - Atrial fibrillation after coronary artery bypass grafting: a comparison of cardioplegia versus intermittent aortic cross-clamping. AB - Supraventricular tachyarrhythmias following coronary artery bypass grafting are a common cause of postoperative morbidity, with a reported incidence of 10-40%. Two techniques of myocardial protection were assessed to determine their influence on the occurrence of postoperative supraventricular tachyarrhythmias. Group I (n = 82) received cold potassium cardioplegia combined with topical hypothermia and systemic cooling to 28 degrees C. Group II (n = 88) were protected by intermittent aortic cross-clamping with a systemic temperature of 32 degrees C. The overall incidence of atrial fibrillation/flutter was 22.3%. No significant difference was detected in the incidence of clinically important atrial fibrillation/flutter between the two groups [21/82 (25.6%) in group I versus 17/88 (19.3%) in group II, P > 0.25]. There was a positive association with age: in patients over 60 years the incidence of arrhythmias (31.8%) was significantly greater than in those less than 60 years (12.9%), P < 0.01. Sex, cardiopulmonary bypass times, aortic cross-clamp times, number of coronary grafts, end-operative creatine kinase myocardial band isoenzyme, right coronary endarterectomy and perioperative myocardial infarction had no association with the occurrence of postoperative atrial tachyarrhythmias. PMID- 8431299 TI - Changes in coronary vasodilatory reserve induced by pressure overload during post natal development: effects on post-ischemic perfusion. AB - Several congenital heart defects result in increased hemodynamic load on one or both ventricles. We have investigated the effects of left ventricular (LV) pressure overload during post-natal development on the coronary vasodilatory reserve in isolated rat hearts (i) during aerobic perfusion, and (ii) following cardioplegic arrest and hypothermic ischemia. The LV pressure overload was induced in 1-week-old Wistar rats by abdominal aortic constriction (AC), with controls (C) undergoing sham operations. Relative to C, the LV weight/body weight in AC increased by 45% and 100% at 3 and 6 weeks of age, respectively. At these ages, the hearts (n = 8/group) were isolated and Langendorff-perfused. Minimal coronary vascular resistance per gram dry weight (MCVR/g) was measured during maximal vasodilation with adenosine (10 mumol/l) before cardioplegic arrest and hypothermic (15 degrees C) ischemia (210 min) and again after reperfusion (45 min). Before ischemia, MCVR/g was greater in AC than in C both at 3 weeks of age (0.48 +/- 0.03 vs 0.31 +/- 0.01 mmHg/ml per min/g dry wt) and at 6 weeks of age (1.20 +/- 0.05 vs 0.46 +/- 0.01 mmHg/ml per min/g dry wt). In the post-ischemic period, MCVR/g increased in all groups. Post-ischemic MCVR/g was similar in C and AC at 3 weeks of age (0.52 +/- 0.12 and 0.66 +/- 0.05 mmHg/ml per min/g dry wt, respectively) but was significantly greater in AC than in C at 6 weeks of age (2.42 +/- 0.22 vs. 0.54 +/- 0.02 mmHg/ml per min/g dry wt).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431300 TI - Reoperation after mitral valve reconstruction: early and late results. AB - Between 1968 and 1990, 68 patients (33 male, 35 female) with a mean age of 47 years were subjected to reoperation (62 valve replacements, 6 reconstructions) after primary mitral valve reconstruction (mean interval = 81 months). The indication for reoperation was residual valve insufficiency in 51, and stenosis in 17 patients. The average preoperative New York Heart Association (NYHA) class was 3.0. The average follow-up was 63 months. The operative mortality was 8.8% (8 out of 68 patients). The actuarial late survival was 90% after 5, and 73% after 8 years. After a second mitral valve reconstruction 66% (four out of six patients) died (one early, three late). The incidence of second reoperations was 4.4% (3 out of 68 patients), and of thromboembolic complications 11.8% (8 out of 68 patients). The mean NHYHA class improved significantly. The actuarial freedom from second reoperations was 98% and 90%, and from thromboembolic complications 91% and 82% after 5 and 10 years, respectively. Endocarditis did not occur, whereas two patients on Coumadin anticoagulation had non-fatal gastrointestinal bleeding. Late survival was less favorable (P < 0.05) in patients operated on before 1980, in a higher preoperative NYHA class, after a second valve reconstruction, and if pulmonary hypertension or atrial fibrillation was present. Significant independent risk factors were older age and earlier reoperation, pulmonary hypertension or higher NYHA class postoperatively. For the last to years it has been possible to perform reoperations after mitral valve reconstructions with good early and excellent late results. The mortality and complication rates were similar to those for primary mitral valve reconstructions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431301 TI - Use of the right gastroepiploic artery as a pedicled arterial graft for coronary revascularization. AB - Between April 1988 and August 1991, the right gastroepiploic artery (RGEA) was used as a pedicled arterial graft for coronary arterial bypass grafting (CABG) in 44 patients. Their ages ranged from 8 to 72 years (mean: 58.7 years), and body size was small for 21 patients (body surface area < 1.6 m2). The mean number of distal anastomoses was 3.2 +/- 0.7 per patient. The RGEA was anastomosed to the right coronary system in 35 patients and to the left in 9 patients. Perioperative vasospasm of the RGEA occurred in 4 patients, but no vasospasm was seen after intraluminal injection of diluted papaverine hydrochloride was used in the last 9 patients. The size of the RGEA at the site of anastomosis was 1.9 +/- 0.4 mm in diameter. The RGEA was harvested in 48 patients; however, two of the RGEAs were smaller than 1.0 mm in diameter and two showed severe calcification with stenosis of more than 75%. Consequently, those conduits were not used. Indications for the use of the RGEA were: relatively young age for 17, matching size of the coronary artery and the RGEA for 11, poor quality of the internal thoracic artery (ITA) or saphenous vein graft (SVG) for 10, lower leg atherosclerosis in 3, a diseased ascending aorta in 2, and Kawasaki disease in 1. The patency rate of the RGEA for 36 patients was 94.4% and relief of angina 95.5%. An exercise tolerance test performed within 2 months after operation showed improved capacity (mean 7.2 metabolic units).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431302 TI - Extended aortic root replacement with pulmonary autografts. AB - The surgical relief of complex multilevel left ventricular outflow tract obstruction remains a challenging surgical problem. We present a new operation which combines the concepts of aortoventriculoplasty, extended aortic root replacement and the use of a pulmonary autograft. Four patients underwent this operation without mortality and morbidity. All patients were in sinus rhythm and showed excellent function of the autograft valve at early follow-up. This operation might present a more durable or even a definitive solution in the management of complex left ventricular outflow tract obstructions. PMID- 8431303 TI - Sandwich repair with two sheets of equine pericardial patch for acute posterior post-infarction ventricular septal defect. AB - A 74-year-old man, who had posterior post-infarction ventricular septal defect, was treated successfully by early surgical repair with a sandwich technique involving two sheets of equine pericardial patch. In this technique the ventricular septal defect (VSD) was exposed through a trans-infarction approach. The inside patch covered the VSD and ventriculotomy from the inside. The outside patch generously covered the infarcted myocardium. The two patches completely sandwiched the infarcted myocardium including the VSD and ventriculotomy with eighteen interrupted sutures. This technique ensures strong fixation of the VSD, reducing the risk of bleeding and recurrence of VSD, and also maintains the proper shape and size of the left ventricle without the danger of ventricular aneurysm formation. PMID- 8431304 TI - The development of heart and heart-lung transplantation at Stanford. Honored guest's lecture. AB - Transplantation of the heart is now accepted and perhaps even routine therapy for patients near death from heart disease. Better, more specific, less toxic molecules are under investigation for the control of rejection. The Holy Grail of tolerance is not beyond the realm of possibility. The mini-chimera concept almost certainly raises the specter of potentially successful xenografts. If not in this decade, certainly in this generation. Transplantation of the heart and both lungs constituted the first successful lung transplant of any kind. The ultimate division of indications for single lung, sequential bilateral lung, or heart-lung transplantation will be settled only by the accumulation of more clinical data. With respect to pulmonary transplantation, a few technical points have become clear. First, the double lung transplant with a tracheal anastomosis has been abandoned owing to the complications of tracheal stenosis and tracheal dehiscence. Second, there is no need to wrap the bronchial anastomosis with omentum; there is no need to "telescope" the donor bronchus. Finally, simple, continuous polypropylene suture technique should be used for any tracheal (heart lung transplantation) or bronchial anastomosis. PMID- 8431305 TI - Aspergillus prosthetic valve endocarditis. AB - A 66-year-old man developed Aspergillus fumigatus endocarditis, complicated by an aortic root abscess 9 months after his aortic valve replacement with a Carpentier Edwards xenograft. The aortic root was replaced with an antibiotic-treated fresh homograft and anti-fungal chemotherapy commenced 24 hours later. One month after this he developed a retrosternal pseudo-aneurysm of the ascending aorta. At re operation the homograft was heavily infected with fungal growths and the patient was considered inoperable. This case is an example of a rare condition complicating cardiac valve prosthesis which still has a very poor prognosis, despite any surgical and chemotherapeutic efforts. PMID- 8431306 TI - Exact positioning of intra-aortic balloon catheter. AB - The positioning of the intra-aortic balloon catheter in the descending aorta is vital for successful balloon pumping. With transesophageal echocardiography, the catheter could be properly and rapidly positioned in the descending aorta. PMID- 8431307 TI - Diagnosis and treatment of bronchial carcinoid tumors: clinical and pathological review of 120 operated patients. AB - Clinical and pathological review is presented of 120 patients operated on for bronchial carcinoid tumors between 1976 and 1986. The usual oncologic features were analyzed. The Grimelius reaction, immunohistochemical staining for neuron specific enolase (NSE), serotonin and chromogranin, and DNA-analysis by flow cytometry were performed in these tumors and in small cell lung cancers (SCLC). In our experience the usual oncologic criteria--atypia, tumor-size, localization, history and regional lymph node metastasis--fail to give clear information for the prognosis. The Grimelius reaction has no significant differential diagnostic importance. Immunostaining for NSE can aid in distinguishing between neuroendocrine and non-neuroendocrine pulmonary tumors. The carcinoids and SCLCs could be differentiated by immunostaining for chromogranin and by flow cytometry but none of these methods are suitable for differential diagnosis within the carcinoid group. Resection by thoracotomy is the only treatment of choice: it can provide an excellent result (the 5-year survival rate is above 90%) with a low hospital mortality (0.8%). Parenchyma-sparing resections are to be encouraged. PMID- 8431308 TI - Biochemical genetics revisited: the use of mutants to study carbon and nitrogen metabolism in the photosynthetic bacteria. AB - The biochemical genetics approach is defined as the use of mutants, in comparative studies with the wild-type, to obtain information about biochemical and physiological processes in complex metabolic systems. This approach has been used extensively, for example in studies on the bioenergetics of the photosynthetic bacteria, but has been applied less frequently to studies of intermediary carbon and nitrogen metabolism in phototrophic organisms. Several important processes in photosynthetic bacteria--the regulation of nitrogenase synthesis and activity, the control of intracellular redox balance during photoheterotrophic growth, and chemotaxis--have been shown to involve metabolism. However, current understanding of carbon and nitrogen metabolism in these organisms is insufficient to allow a complete understanding of these phenomena. The purpose of the present review is to give an overview of carbon and nitrogen metabolism in the photosynthetic bacteria, with particular emphasis on work carried out with mutants, and to indicate areas in which the biochemical genetics approach could be applied successfully. In particular, it will be argued that, in the case of Rhodobacter capsulatus and Rb. sphaeroides, two species which are fast-growing, possess a versatile metabolism, and have been extensively studied genetically, it should be possible to obtain a complete, integrated description of carbon and nitrogen metabolism, and to undertake a qualitative and quantitative analysis of the flow of carbon and reducing equivalents during photoheterotrophic growth. This would require a systematic biochemical genetic study employing techniques such as HPLC, NMR, and mass spectrometry, which are briefly discussed. The review is concerned mainly with Rb. capsulatus and Rb. sphaeroides, since most studies with mutants have been carried out with these organisms. However, where possible, a comparison is made with other species of purple non-sulphur bacteria and with purple and green sulphur bacteria, and recent literature relevant to these organisms has been cited. PMID- 8431309 TI - Regulation and function of rhizobial nodulation genes. AB - This review focuses on the functions of nodulation (nod) genes in the interaction between rhizobia and legumes. The nod genes are the key bacterial determinants of the signal exchange between the two symbiotic partners. The product of the nodD gene is a transcriptional activator protein that functions as receptor for a flavonoid plant compound. This signaling induces the expression of a set of nod genes that produces several related Nod factors, substituted lipooligosaccharides. The Nod factors are then excreted and serve as signals sent from the bacterium to the plant. The plant responds with the development of a root nodule. The plant-derived flavonoid, as well as the rhizobial signal, must have distinct chemical structures which guarantee that only matching partners are brought together. PMID- 8431310 TI - Molecular biology of xylan degradation. PMID- 8431311 TI - Genetics of Paracoccus denitrificans. AB - In bioenergetic research Paracoccus denitrificans has been used as an interesting model to elucidate the mechanisms of bacterial energy transduction. Genes for protein complexes of the respiratory chain and for proteins which are involved in periplasmic electron transport have been cloned and sequenced. Conjugational gene transfer has allowed the construction of site-specific mutant strains. Complementation experiments did not only open the field for site-directed mutagenesis and investigation of the structure/function relationship of the various electron-transport proteins, but also allowed first insights into processes like oxygen-dependent gene regulation or the assembly of electron transport complexes. Also data will be presented that characterize two restriction-/modification systems, the codon usage and the promoter sequences of Paracoccus. Details will be given about the extrachromosomal localization of a duplicated cytochrome oxidase subunit I gene on one of the Paracoccus megaplasmids. PMID- 8431312 TI - How long should patients fast before surgery? Time for new guidelines. PMID- 8431313 TI - Pain relief for infants undergoing abdominal surgery: comparison of infusions of i.v. morphine and extradural bupivacaine. AB - We have undertaken a prospective, randomized double-blind study to compare extradural bupivacaine infusions with i.v. morphine infusions for postoperative analgesia in 32 infants younger than 4 yr undergoing abdominal surgery. "Sham" extradural or i.v. catheters were used to maintain the blinded nature of the study. Both techniques provided adequate analgesia for most of the 36-h postoperative period; differences in the pattern or quality of the analgesia were not detected. Patients in the i.v. morphine group were significantly more sedated; this was accompanied by slower ventilatory frequencies (26.7 (SD 1.8) b.p.m.) compared with the extradural group (33.6 (1.3) b.p.m.). Similarly, oxygen saturation was significantly less (P < 0.01) in patients receiving morphine (medians and quartiles of 94.0 (93-96)% compared with 96.0 (93-96)%). Mean systolic arterial pressure was similar in the two groups and there were no life threatening complications. The lack of sedation was troublesome in three patients in the extradural group. PMID- 8431314 TI - Prolonged use of isoflurane in a patient with tetanus. AB - We describe a patient with tetanus, who received isoflurane for sedation to facilitate controlled mechanical ventilation. Isoflurane was administered for 34 days, resulting in a sustained serum inorganic fluoride ion concentration in excess of 50 mumol litre-1 and a peak serum inorganic fluoride ion concentration of 87 mumol litre-1. Although these concentrations are potentially nephrotoxic, no toxicity was evident clinically. PMID- 8431315 TI - Pharmacokinetic/pharmacodynamic modelling of atracurium. PMID- 8431316 TI - Aspirin, bleeding time and central neural block. PMID- 8431317 TI - Death certification. PMID- 8431318 TI - Sedation with propofol during regional anaesthesia. PMID- 8431319 TI - Ketorolac postoperative analgesia. PMID- 8431320 TI - Patient-controlled analgesia by proxy. PMID- 8431321 TI - Veterinary use of "Xylocaine" spray. PMID- 8431322 TI - Use of the laryngeal mask and face mask by inexperienced personnel. PMID- 8431323 TI - Changes in haemodynamic variables with thiopentone, methohexitone, propofol and etomidate. PMID- 8431324 TI - Antepartum assessment for anaesthesia. PMID- 8431325 TI - Antepartum assessment for anaesthesia. PMID- 8431326 TI - Extra inspiratory work of breathing imposed by cricothyrotomy devices. AB - Using a lung model for spontaneous ventilation, we have assessed the additional work of inspiration imposed by a variety of cannulae ranging from the 12- and 14 gauge intravascular cannulae to the 8.0-mm i.d. adult tracheostomy tube. Work (W) ranged between 9 and 2262 mJ litre-1 and power (W) between 0.2 and 37.7 mW litre 1 min; the smallest values were obtained with the 8.0-mm i.d. adult tracheostomy tube and the 12- and 14-gauge intravascular cannulae gave the largest values. With any given cannula, W and W were influenced by ventilation (tidal volume and frequency) and ventilatory wave pattern of the analogue lung. The results obtained from the 12- and 14-gauge cannulae represent what is probably an excessive inspiratory workload, whereas the other four devices (Portex MiniTrach, 4.0, 6.0 and 8.0 tracheostomy tubes) may be suitable in the short term for relieving airway obstruction and compatible with spontaneous ventilation. PMID- 8431327 TI - Evidence for dynamic phenomena in residual tracheal tube biofilm. AB - It has been proposed recently that a dynamic physical process occurring in the tracheal tube might account for the dissemination of bacteria and biofilm fragments into the lungs during mechanical ventilation, and the subsequent development of ventilator-associated pneumonia. In this study of tracheal tubes from consecutive adult intensive care patients, biofilms were detected radiographically in 45 of 50 tubes, and were found at the lower end of the tube more often than at the upper end (P < 0.005). In 37 of 50 tracheal tubes, the maximum biofilm thickness was equal to or greater than the 0.5 mm required for gas-liquid interaction in a tube with an i.d. of 8.5 mm. In 23 of 50 tubes, wave like patterns were found. Five tubes had no biofilm inside the bevelled tip and another six showed evidence of biofilm loss for a greater distance from the tip. These observations suggest that the distribution of tracheal tube biofilm is caused at least in part by dynamic phenomena in the tracheal tube. PMID- 8431328 TI - Pressure exerted by the laryngeal mask airway cuff upon the pharyngeal mucosa. AB - Ten patients were studied for each of the sizes 2, 3 and 4 laryngeal mask airways (LMA) in order to calculate the pressure exerted by the cuff upon the pharyngeal mucosa. Using a non-invasive method of comparing intracuff pressures recorded both in vitro and in vivo, the transmitted pharyngeal mucosal pressures were calculated over the clinical range of injection volumes. Cuff inflation with the "normal" injection volumes recommended resulted in the residual volumes of the cuffs being exceeded. The intracuff pressures recorded with the mask in situ at these normal injection volumes were in the range 103-251 mm Hg. The calculated transmitted mucosal pressures were substantial for all three sizes of cuff and potentially exceeded the capillary perfusion pressure of the adjacent pharyngeal mucosa, despite apparent pharyngeal accommodation to the mask. PMID- 8431329 TI - Comparison of alfentanil with suxamethonium in facilitating nasotracheal intubation in day-case anaesthesia. AB - We have performed a prospective study in 100 adults (ASA I or II) undergoing day case dental extraction to compare the conditions for intubation and the postoperative sequelae of suxamethonium and alfentanil as adjuncts to propofol. The patients were allocated randomly to two groups comparable in age, sex and weight. Successful intubation was achieved in 100% of the suxamethonium group and 90% of the alfentanil group. Of the patients who received suxamethonium, 74% developed myalgia on the day after surgery, compared with 20% in the alfentanil group (P < 0.001). The proportion of patients who developed sore throat was also less in the alfentanil group than in the suxamethonium group (P < 0.05). The proportion of patients who complained of nausea in the two groups was not significantly different. We conclude that alfentanil, as an adjunct to propofol to facilitate tracheal intubation, is more acceptable to patients than suxamethonium in anaesthesia for day-case surgery. PMID- 8431330 TI - Effect of age, gender and anaesthetic technique on the pharmacodynamics of atracurium. AB - We have measured in 38 patients the plasma concentration profile of atracurium and its effect on the electromyographic first response of the train-of-four. One of three techniques was used to supplement anaesthesia with 66% nitrous oxide in oxygen, 0.9% isoflurane (end-tidal), 0.5% halothane (end-tidal) or midazolam 3-10 mg. A four-parameter threshold pharmacodynamic model was fitted to the data in each patient. Compared with a group of patients anaesthetized with an i.v. technique, the steady-state plasma concentration producing 50% block (Cpss50) was reduced by halothane, and to a greater extent by isoflurane. The rate constant for exit from the effect compartment (k(eo)) correlated negatively with age and was greater in female patients, but unaffected by anaesthetic technique. The values of gamma, the slope of the concentration-response curve, and of the threshold (Cpss theta) were not affected significantly by age, sex or anaesthetic technique. PMID- 8431331 TI - Postoperative analgesia in children. PMID- 8431332 TI - Midazolam-alfentanil: an anaesthetic? An investigation using the isolated forearm technique. AB - Thirty-two women underwent major gynaecological surgery with a midazolam alfentanil total i.v. anaesthetic regimen. Adequacy of anaesthesia was assessed using a "pressure, rate, sweating and tears" (PRST) scoring system in conjunction with the isolated forearm technique (IFT). The IFT revealed that 72% of patients responded during surgery, but none had spontaneous, unprompted postoperative recall for the event. Three patients, on prompting, provided evidence of recall. The IFT, while indicating which patients are responsive, cannot be used to predict who will have postoperative recall. Lack of explicit postoperative recall does not indicate unconsciousness during surgery. Twenty patients, asked specifically during surgery to indicate the presence or absence of pain, experienced pain at some time during their surgical procedure. The PRST score could not be used to predict when a patient was awake. This low-dose i.v. anaesthetic technique cannot be recommended for general use. PMID- 8431333 TI - Effects of etomidate on the adrenocortical and metabolic adaptation of the neonate. AB - The effects of etomidate on corticosteroid synthesis were compared with those of methohexitone. We studied 40 neonates, 22 delivered by elective and 18 by emergency Caesarean section. Apgar scores, blood sugar and plasma concentrations of cortisol and etomidate were evaluated at birth and 2 and 6 h postpartum. There was no difference in Apgar scores attributable to the induction agent. The median cortisol concentrations in cord blood were small (136 nmol litre-1; range 47-478 nmol litre-1, and 259 nmol litre-1; range 58-1504 nmol litre-1 after elective and emergency sections, respectively). During the study, cortisol concentrations increased in the infants in the methohexitone groups and decreased in those in the etomidate groups; this effect was most evident 2 h after delivery (methohexitone groups 245 nmol litre-1, range 70-959 nmol litre-1; etomidate groups 121 nmol litre-1, range 56-320 nmol litre-1). There was no difference at 6 h postpartum (methohexitone groups 183 nmol litre-1, range 25-756 nmol litre-1; etomidate groups 190 nmol litre-1, range 33-628 nmol litre-1). The concentration changes during the study period differed significantly (P < 0.005) with respect to the induction agent. Blood glucose concentrations were small (mean (SD) in all 40 neonates 2 h postpartum was 2.64 (0.77) mmol litre-1), and did not differ between the groups. There were 17 cases of moderate to severe hypoglycaemia (blood glucose concentrations less than 2.5 mmol litre-1): nine in the etomidate group and eight in the methohexitone group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431334 TI - Nitrous oxide-mediated activation of the EEG during isoflurane anaesthesia in patients. AB - We have studied the effects of nitrous oxide on EEG burst suppression patterns during stable isoflurane anaesthesia in 13 ASA I patients. After induction of anaesthesia with propofol, the concentration of isoflurane was increased with continuous EEG monitoring to burst suppression level (mean end-tidal concentration of isoflurane, 1.7 (SD 0.2)%), and kept constant during the study. During surgery, isoflurane in air and oxygen (FIO2 0.35), or isoflurane in 65% nitrous oxide in oxygen were given to each patient for 30 min, in random order. EEG was recorded and digitized off-line. The proportion of EEG suppression time was measured after a washin or washout period of at least 15 min for nitrous oxide. There was a significant decrease in the proportion of EEG suppression time (from 69.5 to 43.7%) when air was replaced by nitrous oxide. We conclude that the EEG effects of isoflurane and nitrous oxide are not additive and that nitrous oxide opposes the depression of isoflurane on the central nervous system. PMID- 8431335 TI - Comparison of thoracic electrical bioimpedance and thermodilution for the measurement of cardiac index in patients with severe sepsis. AB - Cardiac index was measured using thoracic bioimpedance (CIbi) and thermodilution (CItd) in 19 patients with proven sepsis, undergoing artificial ventilation of the lungs. There was a poor correlation between the techniques (r = 0.36, 242 data sets, regression line CIbi = 0.16 CItd + 2.56 litre min-1 m-2). The overall bias (CItd-CIbi) was 1.69 litre min-1 m-2 with limits of agreement (precision) of +4.17 to -0.79 litre min-1 m-2. In individual patients the bias was from -0.46 to 4.56 litre min-1 m-2 with the limits of agreement from +/- 0.29 to +/- 2.55 litre min-1 m-2 around the bias values. The two techniques cannot be used interchangeably in this group of patients. PMID- 8431336 TI - Preoperative drinking does not affect gastric contents. AB - We have compared the effect of allowing free clear fluids until the time of oral premedication with conventional preoperative fasting. In a prospective, randomized trial, the residual volume and pH of gastric contents after induction of anaesthesia were measured in 100 elective surgical patients allocated randomly to a group in whom the intake of free clear fluids up to the time of premedication was measured (mean 388 ml in 6 h before surgery) or a control group who were fasted for 6 h. Preoperative drinking did not affect either mean (SD) residual gastric volume (22 (21) ml in the study group vs 19 (16) ml in the control group) or pH (study group 2.64 (1.57) vs control group 2.26 (1.45)). The study group experienced less preoperative thirst. Problems with aspiration or regurgitation were not encountered. We believe that allowing elective surgical patients to drink clear fluids until 2 h before anaesthesia may enhance patient comfort without compromising safety. PMID- 8431337 TI - Differential effects of alfentanil, fentanyl, pethidine and lignocaine administered intrathecally on nociceptive responses evoked by low and high frequency stimulation of somatic nerves. AB - We have studied in anaesthetized dogs the effects of alfentanil, fentanyl, pethidine and lignocaine administered intrathecally on nociceptive responses evoked by low and high frequency supramaximal electrical stimulation of the tibial and radial nerves. Doses were selected to abolish both A delta and C fibre somatosympathetic reflexes to single stimuli. Pethidine and lignocaine eliminated reflex pressor and heart rate responses to repeated single stimuli and almost completely abolished responses to train stimulation. The pressor response to single stimuli was abolished by fentanyl and reduced by alfentanil, but these drugs did not reduce significantly this response to train stimulation, suggesting a stimulation rate-dependent effect. Of the opioids, only pethidine had an effect comparable to that of lignocaine. The absence of sympathetic block and antagonism by naloxone imply a lack of significant local anaesthetic effect. We suggest that the greater analgesic efficacy of pethidine is a result of endogenous synergism between a minor local anaesthetic and a major opioid effect. PMID- 8431338 TI - Genetic linkage analysis of chromosome 19 markers in malignant hyperthermia. AB - Previous studies have reported that malignant hyperthermia susceptibility is caused in some families by inherited variation in a gene located on the short arm of chromosome 19 near to, or identical with, the ryanodine receptor gene (RYR1); this is expressed in skeletal muscle as a calcium release channel of the sarcoplasm reticulum. In other families, a gene in this location is excluded, but the locations of the genes involved have not yet been defined. We have analysed DNA samples from members of three large British families in whom in vitro muscle contracture tests for malignant hyperthermia susceptibility have been carried out in accordance with the procedure recommended by the European Malignant Hyperthermia Group. The results presented here strongly suggest that the gene for malignant hyperthermia susceptibility in one or more of these three British families is located in the same region of chromosome 19q, although further work is required to decide whether or not the RYR1 gene itself is causative in these families. As genetic heterogeneity could not be excluded, we cannot yet recommend the use of DNA markers to replace in vitro contracture tests in the diagnosis of malignant hyperthermia susceptibility. PMID- 8431339 TI - In vitro effect of ephedrine, adrenaline, noradrenaline and isoprenaline on halothane-induced contractures in skeletal muscle from patients potentially susceptible to malignant hyperthermia. AB - We have measured the effects of ephedrine, adrenaline, noradrenaline and isoprenaline on halothane-induced contractures in muscle biopsies from patients potentially susceptible to malignant hyperthermia (MH). At concentrations of 4-24 mmol litre-1, ephedrine induced in vitro contractures in halothane 0.44 mmol litre-1-prechallenged muscle, whilst adrenaline, noradrenaline and isoprenaline had no effect. There was a shift of the ephedrine concentration-response curve to the left and an increased maximum muscle contracture in the MH susceptible group compared with the MH negative group (P < 0.001). We conclude that ephedrine increased halothane-induced muscle contractures in vitro either by an unknown pharmacological mechanism or by an adrenergic stimulation which was different from those of the other investigated adrenoceptor agonists. PMID- 8431340 TI - The role of recombinant growth factors in transfusion medicine. PMID- 8431341 TI - Intra-articular morphine for pain relief after anterior cruciate ligament repair. AB - We have performed a randomized, double-blind controlled study in patients undergoing elective anterior cruciate ligament repair, to assess the effect of intra-articular morphine on postoperative pain. The morphine group (n = 11) received morphine 5 mg in saline 25 ml and the control group (n = 9), saline 25 ml intra-articularly. Patients in the morphine group had significantly smaller pain scores throughout the 24-h postoperative period compared with those in the control group (P < 0.05). There was less requirement for supplementary analgesics in the morphine group. PMID- 8431342 TI - Use of alfentanil with propofol for nasotracheal intubation without neuromuscular block. AB - We have investigated the effect of augmentation of propofol with alfentanil for nasotracheal intubation without neuromuscular block in 60 patients undergoing short elective maxillo-facial procedures as outpatients. After administration of glycopyrronium 5 micrograms kg-1 i.v., anaesthesia was induced with propofol 2.5 mg kg-1, or alfentanil 20 micrograms kg-1 and propofol 2.5 mg kg-1. The alfentanil group had improved jaw relaxation (P < 0.001) and vocal cord conditions (P < 0.005). Tracheal intubation was successful in 83% of patients receiving alfentanil, and in 73% of patients receiving propofol only. This difference was not significant. The cardiovascular response to intubation was attenuated in the alfentanil group. PMID- 8431343 TI - Effect of isometric thumb preload on the evoked compound muscle action potential. AB - The effect of thumb preload on adductor pollicis muscle compound action potential (ECAP) was assessed after supramaximal ulnar nerve stimulus during steady isoflurane anaesthesia in 20 ASA I-II patients without neuromuscular block. During thumb preload, the peak-to-peak amplitude of the ECAP increased by 0.9 mV, to 9.5 (SD 2.2) mV (P < 0.01), because of the increased height of the negative half-wave. The positive half-wave amplitude did not change, but its duration was prolonged by 0.7 ms, to 6.4 (0.7) ms (P < 0.05). Consequently, there was a 15.9% increase in the area of the response curve (P < 0.01). Without preload, the first dorsal interosseus muscle peak-to-peak amplitude was 13.0 (4.3) mV. Thus thumb preload may not be the solution to improved monitoring of neuromuscular block by ECAP. PMID- 8431344 TI - Glycopyrronium prolongs topical anaesthesia of oral mucosa and enhances absorption of lignocaine. AB - We have studied the effect of glycopyrronium on the anaesthetic action and absorption of topical lignocaine in 10 healthy, non-smoking volunteers. Lignocaine 100 mg was sprayed on the oral mucosa 15 min after random administration of glycopyrronium 4 micrograms kg-1 or normal saline i.v. Glycopyrronium decreased the mean analgesia score from 2 to 0.1 (2 = baseline; 0 = anaesthesia) at 4 min compared with a change from 2 to 0.5 after normal saline (P < 0.05). All scores returned to baseline by 40 min and 20 min in the glycopyrronium and control groups, respectively. The mean (SD) peak plasma lignocaine concentration was 0.57 (0.29) microgram ml-1 after glycopyrronium and 0.31 (0.10) microgram ml-1 after saline (P < 0.05) and were attained in 17 min (range 10-40 min) and 29 min (range 8-40 min), respectively. Pretreatment with glycopyrronium enhanced absorption and prolonged the analgesic action of topically administered lignocaine. PMID- 8431345 TI - Haemodynamic and metabolic consequences of aortic occlusion during abdominal aortic surgery. AB - We have studied the haemodynamic and metabolic effects of application and removal of the infrarenal aortic crossclamp in 20 patients during aortic reconstructive surgery for repair of aneurysmal or occlusive disease. A highly significant positive correlation was detected between the change in systemic vascular resistance (SVR) associated with application of the aortic crossclamp and the change in base deficit (BD) associated with its removal (r = 0.851; P = 0.001). There was no difference in regression analysis (P = 0.21) or mean change of SVR and BD (P = 0.73) in patients with either aneurysmal or occlusive disease. In addition, the maximum increase in mixed venous serum lactate concentration correlated positively with the duration that the aortic crossclamp was applied (r = 0.717, P = 0.0297). These observations suggest the importance of the collateral circulation in the development of metabolic acidosis during aortic surgery. PMID- 8431346 TI - Propofol decreases random and chemotactic stimulated locomotion of human neutrophils in vitro. AB - We have studied the influence of clinical concentrations of propofol (2,6 diisopropyl phenol), emulsified propofol (Diprivan) and the emulsifier of propofol (Intralipid 10%) on random and chemotactic locomotion of human polymorphonuclear leucocytes in an agarose assay. Random locomotion was decreased (P < 0.001) to a similar extent by the three drugs. Concentrations of propofol 2.5 micrograms ml-1 and greater, and of Diprivan 3.33 micrograms ml-1 and greater, also reduced chemotaxis (P < 0.05) against both zymosan-activated human serum (C5a) and N-formyl-methionyl-leucylphenylalanine (FMLP), used as chemoattractants. Intralipid reduced chemotaxis towards C5a but not towards FMLP. We conclude that propofol in clinically relevant concentrations may adversely affect leucocyte locomotion in vitro. PMID- 8431347 TI - Expanded programme on immunization. Poliomyelitis in 1991. PMID- 8431348 TI - Global health situation. III. Mortality. PMID- 8431349 TI - Rabies. Extension of the raccoon rabies epizootic, 1992. PMID- 8431350 TI - Leishmaniasis epidemic in southern Sudan. PMID- 8431351 TI - Global health situation. IV. Selected infectious and parasitic diseases due to identified organisms. PMID- 8431352 TI - Expanded programme on immunization. Measles outbreak. PMID- 8431353 TI - Apoptosis (the 1992 Frank Rose Memorial Lecture). AB - Apoptosis is a mode of cell death with characteristic structural features. These appear to result from a set of discrete cellular events that are regulated by gene expression. Oncogenesis and oncosuppressor genes are involved in this regulation. The role of c-myc is of particular interest, as it can act as a bivalent regulator, determining either cell proliferation or apoptosis, depending on whether free movement around the cell cycle is supported (by growth factors) or is limited by growth factor deprivation or treatment with other cycle-blocking agents. In vivo, c-myc expression may be associated with a 'high-turnover' state in which cell proliferation and apoptosis co-exist. Certain other oncogenes (e.g. ras, bcl-2) rescue cells from susceptibility to apoptosis and so convert this high-turnover state into rapid population expansion. One role of the oncosuppressor gene p53 may be to initiate apoptosis by causing G 1/S arrest in cells expressing c-myc. Some aspects of resistance and sensitivity to chemotherapeutic agents can be explained on the basis of movement between the population-expansion and the high-turnover states, perhaps through modulation of the expression of these and other genes. PMID- 8431354 TI - Dosage and cycle effects of dacarbazine (DTIC) and fotemustine on O6-alkylguanine DNA alkyltransferase in human peripheral blood mononuclear cells. AB - There is increasing experimental evidence to suggest that endogenous expression of O6-alkylguanine-DNA-alkyltransferase (ATase) is a major factor in cellular resistance to certain chemotherapeutic agents including dacarbazine (DTIC). We have recently shown wide interindividual variation in the depletion and subsequent regeneration of ATase in peripheral blood mononuclear cells (PMCs) following DTIC and this has now been extended to ascertain whether or not depletion is related to dosage of DTIC used and repeated treatment cycles of chemotherapy. ATase levels were measured in three groups of 25 patients (pts) up to 24 h after receiving DTIC at 400 mg m-2, 500 mg m-2 or 800 mg m-2. Each group also received fotemustine (100 mg m-2), 4 h after DTIC. The lowest extent of ATase depletion (highest nadir ATase) was seen in patients receiving 400 mg m-2. The mean nadir ATase, expressed as a percentage of pre-treatment ATase, was respectively 56.3%, 26.4% and 23.9% for 400 mg m-2, 500 mg m-2 and 800 mg m-2. The median nadir of ATase activity for pts receiving 800 mg m-2 pts was at 4-6 h and for pts given lower doses it was at 2-3 h. In addition, repeated measures analysis of variance of observations before chemotherapy, then at 2, 3, 4, 6 and 18 h after chemotherapy provides some evidence that ATase was depleted to a lesser extent after cycle 1 than after subsequent cycles (P = 0.025). It also provides evidence that the change in ATase activity over time varied with dose and cycle. The findings can be interpreted on the basis of a dosage-dependent metabolism of DTIC to an agent capable of methylation of DNA and subsequent depletion of PMC ATase: with higher DTIC doses, the extent of ATase depletion may be limited by the pharmacokinetics of DTIC metabolism. PMC ATase was measured in another group of 8 pts at various times after receiving only fotemustine (100 mg m-2) and in contrast to DTIC, no ATase depletion was seen suggesting that insufficient concentrations of fotemustine and/or its metabolites were available to react with DNA to produce a depletion of PMC ATase activity. PMID- 8431355 TI - The clonogenic growth of advanced breast tumour lesions adds no value to that of established clinical prognosticators for survival. AB - We measured the clonogenic growth of 110 breast cancer samples obtained from 107 patients with advanced disease. We determined clonogenicity under conventional conditions and under conditions supplemented with growth factors and hormones that target breast tissue. After a median follow-up period of 6 years we analyzed our data to determine if and to what degree clonogenic growth of metastatic breast tumours was related to the survival of patients. We found that tumour clonogenicity and patient survival correlated weakly, particularly if compared to the strong correlations of patient survival with either performance status or tumour bulk. Furthermore, an association between tumour clonogenicity and patient survival was visible only for clonogenicity that was determined under hormone supplemented conditions, and only for tumour lesions that formed 50 or more colonies per 500,000 cells cultured. Thus, we conclude that clonogenic growth of breast tumour samples incompletely reflects the tumour features that determine the course of advanced disease. PMID- 8431356 TI - Effects of suramin on cell-cycle kinetics of MCF-7 human breast cancer cells in vitro. AB - The polyanionic compound suramin can inhibit the proliferation of cells of various origin, including from breast cancer. We have studied the effects of suramin on cell cycle kinetics and distribution of MCF-7 human breast cancer cells in vitro. It was found that both under serum-containing and serum-free culture conditions, and in the absence or presence of oestradiol or insulin-like growth factor-1, prolonged exposure (> or = 48 h) to suramin caused an accumulation of surviving cells in the G2/M-phase of the cell cycle. At a concentration of more than 100 micrograms ml-1 suramin significantly inhibited cell proliferation. The observed effects of suramin on breast cancer cells in vitro, i.e. antiproliferative effects and accumulation of cells in the G2/M-phase of the cell cycle, may have beneficial consequences in the application of treatment strategies based on a combination of suramin with cell cycle specific drugs or radiation therapy. PMID- 8431357 TI - Syrian hamster embryo cell lines useful for detecting transforming genes in mouse tumours: detection of transforming genes in X-ray-related mouse tumours. AB - The Syrian hamster embryo cell lines, SHOK and MC-1, were used as recipient cells for DNA transfection assay to detect transforming genes in experimental mouse tumours. A mouse repeat sequence was utilised to check whether each transformed focus included mouse genomic DNA in the Hamster background. We investigated five mouse tumours that are related to X-ray radiation, and detected activated c-K ras, c-mos, and c-cot oncogenes which induced foci of hamster cells. These results show that SHOK and MC-1 cells have unique properties for detecting transforming genes in experimental mouse tumours. PMID- 8431358 TI - Chemotherapeutic efficacy of the protein-doxorubicin conjugates on multidrug resistant rat hepatoma cell line in vitro. AB - In vitro studies were initiated to study the antitumour effect of protein doxorubicin (DXR) conjugate on the growth of the multidrug resistant rat ascites hepatoma cell line, AH66DR. The 50% inhibitory concentration (IC50) for DXR in AH66DR cell line was 16 mumol l-1 (AH66 parental cell line, AH66P, IC50 was 0.08 mumol l-1). Treatment of AH66P and AH66DR cells with various concentrations of DXR or conjugates at equivalent concentrations of DXR was performed. The two types of conjugates used were bovine serum albumin (BSA)-DXR conjugate and immunoglobulin G (IgG)-DXR conjugate. Both of these conjugates showed potent dose dependent inhibition of cell growth against AH66DR cells as compared with the cells treated with DXR or other controls. The IC50 for BSA-DXR and IgG-DXR conjugates in AH66DR cell line was 0.05 (equivalent DXR) mumol l-1 and 0.07 (equivalent DXR) mumol l-1, respectively. These values were similar to that of the AH66P treated with DXR. Cellular uptake and accumulation of DXR or BSA-DXR conjugate was also quantitated in both cell lines. The cellular concentration of DXR in AH66DR cells was 2-fold lower than that of AH66P cells throughout the experiment. In contrast, by the treatment of AH66DR cells with BSA-DXR conjugate, the intracellular drug concentration increased as a function of time up to 24 h (639.1 +/- 41.8, equivalent DXR, ng 10(-5) cells) and reached the same drug level as AH66P cells treated with DXR (617.9 +/- 17.3 ng-5 cells). Ammonium chloride treatment inhibited the effects of the conjugates but did not inhibit the free drugs. Intracellular DXR was effluxed rapidly from AH66DR cells, but BSA-DXR conjugate remained in the cells at relatively high concentration for a long time. These results indicate that by chemically modifying DXR, such as by conjugation of the drug with proteins, it may be possible to overcome multidrug resistance. PMID- 8431359 TI - A recombinant single chain antibody interleukin-2 fusion protein. AB - Recombinant interleukin-2 (rIL-2) therapy has been shown to be of value in the treatment of some cases of melanoma and renal cell carcinoma. However its use can be limited by severe systemic toxicity. Targeting rIL-2 to the tumour should improve the anti-tumour immune response and decrease the systemic toxicity. With this aim we have employed recombinant DNA techniques to construct a single chain antibody interleukin-2 fusion protein (SCA-IL-2). The protein used in this model system comprises the variable domains of the anti-lysozyme antibody D1.3 fused to human IL-2. It has been expressed by secretion from Escherichia coli and the purified product possesses antigen binding specificity and retains the immunostimulatory activities of rIL-2. This approach can be taken to generate SCA IL-2 proteins that bind to appropriate cellular antigens. In vivo administration of a tumour binding SCA-IL-2 should result in a localised high concentration of IL-2 in tumour tissues, maximising the anti-tumour immune response, whilst keeping systemic side effects to a minimum. PMID- 8431360 TI - Metabolism of the bioreductive cytotoxin SR 4233 by tumour cells: enzymatic studies. AB - SR 4233 (3-amino-1,2,4-benzotriazine 1,4-dioxide) is an anti-tumour agent that has a highly selective toxicity to hypoxic cells. In this study we delineate the role of several different bioreductive enzymes in the metabolism of SR 4233 by two tumour cell lines HT 1080 (human fibrosarcoma) and SCCVII (mouse carcinoma). Enzyme kinetics demonstrates similar KM of HT 1080 and SCCVII cell sonicates and differing Vmax. Among all cofactors tested, NADPH was the most important one in reducing SR 4233 by both tumour cell sonicates. NADH was the second most important cofactor while hypoxanthine and N-methylnicotinamide were less involved in the reduction of SR 4233. Carbon monoxide inhibited the reduction by about 60% suggesting that cytochrome P-450 may play a major role in the reduction of SR 4233 under hypoxia in both SCCVII and HT 1080 cells. DT diaphorase is also involved, particularly in HT 1080 cells, in this drug reduction. The level of functional cytochrome P-450, cytochrome P-450 reductase activity and DT diaphorase activity in both cell lines were assayed. These enzyme levels were all higher in SCCVII cells than in HT 1080 cells. This result correlated the higher Vmax of SR 4233 reduction in SCCVII cells than in HT 1080 cells. PMID- 8431361 TI - Completeness of cancer registration in England and Wales: an assessment based on 2,145 patients with Hodgkin's disease independently registered by the British National Lymphoma Investigation. AB - Records of 2,145 cases of Hodgkin's disease in England and Wales treated by the British National Lymphoma Investigation during 1970-84 were sought in the national and regional cancer registers. One thousand eight hundred and eight-six (88%) were recorded in the national register, either as Hodgkin's disease (86%) or as other or unspecified lymphoma (2%) and 2 (0.1%) were recorded as other cancers. A further 69 (3%) cases were registered by regional cancer registries but had not reached the national register. Adjusting for the distribution of the study cases by region of incidence, we estimate completeness of registration of cases of Hodgkin's disease in the national register at 89.7%, and in the regional registers overall at 92.9%. Completeness did not vary appreciably by age or sex or calendar period. There was however, substantial variation in completeness between regional registries. Estimates were made for all regions except North Western; the lowest estimated completeness were under 90% in Wessex, and the Thames registry regions, and the greatest were 95% or more in Northern, Trent, East Anglia, Oxford, South Western, West Midlands and Mersey. Because these results are confined to one malignancy treated by a particular collaborative network of physicians (although a large and widespread one), and because the patients are restricted to those seen in hospitals, caution must be exercised in extrapolation of the findings to cancer registration generally, but other studies and sources of information lead to similar conclusions about completeness of cancer registration nationally and regionally. PMID- 8431362 TI - Thyroid cancer epidemiology in England and Wales: time trends and geographical distribution. AB - Thyroid cancer incidence has been increasing in many countries, whereas mortality has been falling due to better survival. Radiation is the best-established risk factor and there has been concern that recent rises in incidence might be related to fallout radiation from atmospheric nuclear weapon tests. We examined thyroid cancer time trends and geographical distribution in England and Wales and possible interpretations of these. During 1962-84, there were significant increases in incidence (P < 0.001) in each sex at ages under 45. Cohort analysis by single year of birth showed an overall increase in incidence risks in women aged 0-44 born since 1920, with a sudden rise in risk for the birth years 1952-55 followed by a lower risk for the more recent cohorts. In men, there was an overall increase in risk at ages 0-44 in successive birth cohorts, but the pattern was irregular. In each sex, the risk in persons aged 45 and over decreased slightly in successive generations. Geographically, highest incidence risks were in countries in North and Mid Wales, in which the risk was almost twice that in the rest of the country. This pattern was present only at ages 45 and over and was most clear in rural areas. The peak of thyroid cancer risk in women born in 1952-55 is consistent with a carcinogenic effect of fallout radiation, since these women were children in the late 1950s and early 1960s when fallout radiation was greatest in England and Wales. The focus of high thyroid cancer risks in Wales was in areas with high levels of fallout radiation. However, thyroid cancer risks in Wales were not high for more recent cohorts (the ones who were exposed to fallout early in life), and a focus on high risk of benign thyroid diseases was present in Wales well before nuclear weapons existed. The distributions of these benign thyroid diseases, or of factors causing them, seem more likely than fallout to explain the high risk areas for thyroid cancer in the country. PMID- 8431363 TI - A daily diary for quality of life measurement in advanced breast cancer trials. AB - The Qualitator is a daily diary card to measure Quality of Life, developed for use in chemotherapy trials for patients with advanced breast cancer. In a trial at King's College Hospital, 29 patients completed the Qualitator and their scores were compared with scores in the Linear Analogue Self-Assessment and Nottingham Health Profile taken four-weekly. In a separate study at Guy's Hospital, 31 patients completed the diary. The Qualitator offers accurate prognostic data regarding subsequent UICC response and survival and is simple to use. PMID- 8431364 TI - Risk of leukaemia after chemotherapy in a case-control study in Moscow. AB - In a case-control study of second primary cancers in Moscow, there were 165 cases and 294 controls, matched for site of first primary, duration of follow-up since first primary and relapse history. Of the cases, 18 were of acute, non lymphocytic leukaemia (ANLL), with 39 matched controls. Risk of ANLL was assessed with respect to chemotherapy for the first primary tumour. The chemotherapeutic agents investigated were nitrogen mustard, cyclophosphamide, procarbazine, doxorubicin, bleomycin, vinblastine, vincristine, prednisone and combinations. Increased risks were associated with use of nitrogen mustard (odds ratio = 9.94, not significant), doxorubicin (odds ratio = 11.25, 0.1 > P > 0.05) and vincristine (odds ratio = 26.57, P < 0.05). Despite the small number of cases and potential confounding by other agents, these findings, together with those of previous studies, suggest that some non-alkylating agents may predispose to second malignancies. PMID- 8431365 TI - Age, socio-economic status and survival from cancer of cervix in the West of Scotland 1980-87. AB - The outcome of treatment by age and socio-economic status was examined for 1,588 women with invasive cancer of cervix resident in the West of Scotland and diagnosed between 1980 and 1987. There was no difference in prognosis according to either variable once analysis was controlled for stage at presentation, treatment type and tumour grade. Tumour histology, date of treatment and health board of residence had no significant effect on survival independent of other variables. A strong correlation was found between socio-economic status and the incidence of cervical cancer in the West of Scotland. Women aged 45 and over and living in deprived areas were more likely to present with later stage tumours and to survive less well than younger patients from the more affluent parts of the region. Any additional resources which may be made available for cervical cancer screening should be directed more effectively towards those most at risk. PMID- 8431366 TI - Uptake and retention of estramustine and the presence of estramustine binding protein in malignant brain tumours in humans. AB - Estraumustine phosphate (EMP), a cytotoxic drug used in the treatment of prostatic carcinoma, has been shown to exert cytotoxic effects on glioma cells in vitro. The drug uptake is assumed to depend on a specific estramustine binding protein (EMBP). One of the main difficulties in achieving cytotoxic effect in malignant brain tumours is believed to be due to the poor penetration of cytotoxic drugs into tumour tissue. In patients with malignant supratentorial brain tumours we have analysed the uptake of EMP metabolites in tumour tissue after oral administration and demonstrated EMBP in the same tissue specimens. Sixteen patients were given 280 mg EMP orally 14 h prior to surgery. Specimens from brain tumour tissue, cystic fluid, and serum were collected during surgery. Using gas chromatography the metabolites of EMP, estramustine (EaM) and estromustine (EoM), were quantified, EMBP was demonstrated by immunohistochemistry. The mean concentrations of EaM and EoM, expressed in ng g 1, were 60.3 and 38.4 in tumour tissue and 3.5 and 56.3 in serum, respectively. An accumulation of EaM in tumour tissue was found with a mean concentration gradient of 16.1 versus serum, while the gradient for EoM was 0.76. EMBP was demonstrated with a high degree of staining in all but one tumour. The high concentrations of EaM and EoM found in malignant brain tumour tissue correspond to potentially cytotoxic levels. The present results as well as the earlier in vitro demonstrated cytotoxic effects on glioma cells strengthen the possibility of a therapeutic effect of EMP in the treatment of malignant brain tumours. PMID- 8431367 TI - Preclinical, phase I and pharmacokinetic studies with the dimethyl phenyltriazene CB10-277. AB - Decarbazine is an imidazole dimethyltriazene with reproducible activity in patients with metastatic melanoma. CB10-277 is a phenyl dimethyltriazene which, like dacarbazine, requires metabolic activation to its corresponding monomethyl species for antitumour activity. In preclinical models (human melanoma xenografts and transplantable rodent tumours) CB10-277 showed a similar spectrum and level of activity when compared to dacarbazine. Pharmacokinetic studies were performed with CB10-277 in mice treated i.v. at the LD10 (750 mg m-2) and plasma analysed by HPLC. The parent drug area under the plasma concentration vs time curve (AUC) was 142 mM x minutes. Drug metabolism occurred as evidenced by the HPLC identification of the monomethyl species (AUC = 8 mM x minutes) as well as other metabolites. A Phase I trial using a short infusion with doses repeated every 21 days has been performed. Thirty-six patients received 80 courses over a dose range of 80-6,000 mg m-2. The dose limiting toxicity was nausea and vomiting which occurred in 80% of the evaluable courses > or = 900 mg m-2. The only other common side effect was a flushing or warm sensation, which occurred in over 75% of courses at > or = 1,350 mg m-2. There were no hemodynamic consequences. Responses occurred in patients with melanoma (one complete, two partial, one mixed/11), sarcoma (one mixed/6) and carcinoid (one partial/l). Pharmacokinetics were performed in 46 courses. The CB10-277 AUC increased linearly with dose (r = 0.9203, P < 0.001) up to 700 mM x minutes at 6,000 mg m-2). Evidence of CB10-277 metabolism was observed, as in mice, by detection of the monomethyl species and other metabolites. However, the plasma levels of the monomethyl species in patients (1.8 and 3.7 mM x minutes at 6,000 mg m-2) were less than those predicted from studies in mice. Despite this, antitumour activity in dacarbazine sensitive histologies was observed and additional studies with CB10-277 are recommended. PMID- 8431368 TI - Phase I trial with pharmacokinetics of CB10-277 given by 24 hours continuous infusion. AB - The dose limiting toxicities of the short infusion trial of the dacarbazine analog, CB10-277, were nausea and vomiting which appeared to be related to the peak plasma level of the parent drug. In addition, based on mouse studies, these dose limiting toxicities occurred at a less than optimal level of the monomethyl metabolite, the presumed species required for antitumour activity. An alternative schedule that would avoid the parent drug peak plasma levels of short infusion, while possibly allowing an increase in the amount of monomethyl metabolite produced was considered. Thus, a 24 h continuous infusion schedule, repeated every 21 days was explored. Twenty-two patients received 42 courses with a dose range of 4,700-15,000 mg m-2. The dose limiting toxicity was myelosuppression (leucopenia and thrombocytopenia). Although nausea and vomiting also occurred, it was manageable with routine antiemetic therapy. Other toxicities included diarrhoea, hallucinations, malaise, muscle ache, headache and flushing and all were < or = WHO grade 2. Pharmacokinetic studies were performed with 13 courses which included all dose levels. The mean t1/2 of the parent drug was 178 min. Area under the concentration x time curve (AUC) at the highest dose for the parent drug and the monomethyl metabolite were 2,350 and 9 mM x minutes, respectively. This monomethyl metabolite AUC and the associated myelosuppression showed a more favourable comparison to the preclinical data determined in mice than the results from the short infusion trial of CB10-277. Therefore, the recommended Phase II dose and schedule of this drug was 12,000 mg m-2 given by 24 h continuous infusion. PMID- 8431369 TI - Breast cancer prognosis is poor when total plasminogen activator activity is low. AB - Plasminogen activator (PA) is a serine protease which exists in two forms: tissue type (t-PA) and urokinase-type (u-PA). The total PA activity was measured in tumour extracts of 235 breast cancer patients who were followed for a median of 8.5 years after surgery. Patients were initially divided into three groups with low (< 60 units mg-1 protein), intermediate (60-300 unit mg-1 protein), or high (> 300 unit mg-1 protein) total PA activity in tumour extracts. The PA activity was not significantly associated with the recognised prognostic factors of age, menstrual status, tumour size, lymph node involvement, histologic type, grade of anaplasia, and/or vessel involvement. A significant association was found between total PA activity and the oestrogen receptor (ER) or progesterone receptor (PgR) status. Among receptor-positive tumours, a significantly greater proportion of patients had high PA activity in their tumour extracts. Breast cancer patients with low total PA activity had a significantly shorter disease-free and overall survival rate when compared to those with intermediate or high PA activity. In univariate and multivariate analyses, total PA activity (< 60 unit mg-1 vs > or = 60 unit mg-1 protein) was found to be a significant prognostic factor for disease free and overall survival of about the same import as lymph node involvement. Furthermore, the combination of total PA activity and nodal status could be even more precise in predicting survival times and probabilities in individual patients. This retrospective study demonstrates the total PA activity is a valuable prognostic factor in determining prognosis in human breast cancer. PMID- 8431370 TI - Hormonal treatment of pancreatic carcinoma: a phase II study of LHRH agonist goserelin plus hydrocortisone. AB - Eighteen consecutive patients with measurable locally advanced or metastatic pancreatic adenocarcinoma were treated with goserelin (Zoladex) 3.6 mg subcutaneously every 4 weeks. Hydrocortisone 20 milligrams twice daily was commenced with the second injection of goserelin. Objective tumour response was monitored by computerised tomography of the abdomen. There was no objective remission in disease sites. Serial measurements of serum tumour markers showed no reduction in serum CA 19-9 and CA 195 concentrations. The median duration of survival of all cases was 5 months. Administration of goserelin resulted in significant reductions in oestradiol, testosterone, androstenedione in males and reductions in FSH and LH in both males and females. The addition of hydrocortisone resulted in further reductions of androstenedione and testosterone levels in males. Thus goserelin showed no anti-tumour effect, but concentrations required for direct inhibitory effects may be higher than those required to produce effects on hormone suppression. PMID- 8431371 TI - Autologous transplantation in poor risk Hodgkin's disease using high dose melphalan/etoposide conditioning with non-cryopreserved marrow rescue. The Newcastle and Northern Region Lymphoma Group. AB - This study aimed to assess the safety and efficacy of using high dose melphalan and etoposide followed by autologous, non-cryopreserved marrow rescue in advanced Hodgkin's disease (HD). Seventeen patients with poor risk Hodgkin's disease from a single centre underwent autologous bone marrow transplant (ABMT) using high dose melphalan and etopside conditioning. Two patients had primary progressive resistant disease (PD), two were in fourth relapse, six in second or third complete remission (CR), one patient had good partial response (GPR) (> 75% reduction in initial bulk) to primary therapy and six were in first complete remission. The patients transplanted in first CR all has a Scotland and Newcastle Lymphoma Group (SNLG) Prognostic Index (Proctor et al., 1991) which indicated they were in a poor risk prognostic group. Melphalan and etoposide both have a short half life enabling ABMT to be accomplished using unmanipulated marrow stored at 4 degrees C. The marrow was returned to the patient within 56 h of harvest. Complete haematological reconstitution occurred in 16/17 patients, the rate of engraftment reflecting the amount of previous chemotherapy. One patient died of progressive Hodgkin's disease before full engraftment could occur. In patients autografted in first remission, the median number of days with neutropenia (< 0.5 x 10(9) l-1 neutrophils) was 19 (range 9-33) and, in those in subsequent remission, 27 days (range 18-36). The median number of days to 50 x 10(9) l-1 platelets in the same groups were 29 (21-80) and 50 (41-74) respectively. The number of days in hospital post transplant in both groups was similar; median 22 (15-27) and 23 (17-37) respectively. There were no procedural deaths and none of the patients transplanted in first, second or third CR have relapsed (median follow up 21 months). The two patients transplanted with progressive disease showed only temporary responses. The two patients transplanted in fourth relapse went into CR; one is still alive and in CR 15 months post transplant, but the other relapsed 18 months post transplant. This form of intensification therapy with marrow rescue has been shown to be effective and of low toxicity and now forms part of a randomised controlled trial in poor risk Hodgkin's patients as identified by the SNLG index (Proctor et al., 1992). PMID- 8431373 TI - Multiple primary cancers in the Vaud Cancer Registry, Switzerland, 1974-89. AB - Data collected by the Cancer Registry of the Swiss Canton of Vaud (whose population in 1980 was about 530,000 inhabitants) were used to estimate the incidence of second metachronous primary cancers following any specific neoplasm. Among 34,615 cases of incident neoplasms registered between 1974 and 1989 and followed through integrated active follow-up to the end of 1989, for a total of 118,241 person-years at risk, there were 2,185 second primaries (1,280 males, 905 females). For both sexes, the standardised incidence ratios (SIR) were significantly elevated by about 20%. Overall significantly elevated ratios were registered for cancers of the oral cavity and pharynx (SIR = 1.6 for males, 2.0 for females), oesophagus in males (SIR = 1.5), lung in males (SIR = 1.4), skin melanoma (SIR = 1.7 for males, 1.5 for females), non-melanomatous skin cancers (SIR = 1.6 for males, 1.5 for females), female breast (SIR = 1.3), kidney (SIR = 1.5 for males, 1.9 for females), and thyroid in males (SIR = 2.4). When specific first cancer sites were considered, the SIR following a cancer of the oral cavity and pharynx was around 3 in both sexes, mainly on account of a substantial excess of second primaries of the oral cavity, oesophagus, larynx and lung. The overall SIR following laryngeal cancer was 3.0, and significant excesses were observed for oral cavity and pharynx, oesophagus and lung. After lung cancer, the overall SIR was 1.7 for males and 2.6 for females, and significantly elevated SIRs were observed for oral cavity, lung and oesophagus. Following non-melanomatous skin cancers, elevated SIRs were observed in both sexes for skin melanoma and non melanomas. The incidence of any cancer after breast cancer was significantly elevated (SIR = 1.2), mainly on account of an elevated risk of subsequent breast cancer (SIR = 1.7). With reference to cervical cancer, there was a significant excess for any subsequent primary (SIR = 1.6), and for lung cancer (SIR = 7.8). Significantly elevated SIRs were observed for kidney following bladder cancer, and for bladder after kidney cancer. In both sexes, the incidence of cancers of any site was elevated following leukaemias (SIR = 1.7 for males, 2.5 for females), and a significant excess was registered for lung in males and non melanomatous skin cancers in both sexes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8431372 TI - Oral piritrexim, an effective treatment for metastatic urothelial cancer. AB - Piritrexim is a lipid-soluble inhibitor of dihydrofolate reductase (DHFR) that enters tumour cells rapidly by passive diffusion, cannot be polyglutamated, and is as effective as methotrexate in inhibiting DHFR. Bioavailability after oral dosing is approximately 75%. We performed a phase II study with oral piritrexim in non-chemotherapy pretreated patients with metastatic urothelial cancer. Thirty three patients were treated with 25 mg three times daily for 5 consecutive days, repeated weekly, with provision for dose escalation or reduction according to the toxicity observed. Of 29 evaluable patients, one patient achieved a complete response of 19+ weeks duration, and ten patients achieved a partial response with a median duration of 22 weeks (range 16-48), for a total response rate of 38%. Piritrexim was generally well tolerated, with myelosuppression as the major toxicity, that frequently required dose modification. We conclude that piritrexim appears to be an active agent in patients with metastatic urothelial cancer when administered as a 5-day, low-dose oral schedule. It would be attractive to investigate the combination of piritrexim and cisplatin. PMID- 8431374 TI - A phase I study of 1,2-diamminomethyl-cyclobutane-platinum (II)-lactate (D-19466; lobaplatin) administered daily for 5 days. AB - A phase I trial was conducted with lobaplatin (D-19466; 1,2-diamminomethyl cyclobutane-platinum (II)-lactate) i.v. bolus daily for 5 days every 4 weeks. After entering five patients toxicity appeared to be related to renal function, therefore the individual dose (total dose 20-100 mg m-2 over 5 days) of lobaplatin was modified according to creatinine clearance (CRCL) and escalated in patients. Twenty-seven patients with refractory solid tumours received 72 courses. Thrombocytopenia was dose-limiting, its degree was related to dose and CRCL at time of drug administration. With a CRCL of 60-80 ml min-1 the maximum tolerated dose was 40 mg m-2, with a CRCL of 81-100 ml min-1 70 mg m-2, and with a CRCL > 100 ml min-1 it was 85 mg m-2. Platelet and leukocyte nadirs were observed around day 21. The percentual platelet nadir (percentage of day 1 platelet count) correlated with CRCL at different dose levels and could be described by 0.76 x CRCL (ml min-1) - (1.45 x dose (mg m-2) + 43.38. This equation tested in 20 patients (28 courses) produced a correlation between observed and predicted percentual platelet nadir (r = 0.82, P < 0.001). No renal function impairment occurred. Urinary excretion of platinum (by A.A.S) was estimated in six patients and revealed that 91.5% (s.e. +/- 7.9) of the platinum dose was excreted within 4 h. Responses (one PR, one CR) occurred in two patients with ovarian cancer (both pretreated with carboplatin and cisplatin). The recommended dose of lobaplatin i.v. bolus daily for 5 days for phase II studies depends on renal function, namely 30 mg m-2 at CRCL 60-80 ml min-1; 55 mg m-2 at CRCL 81-100 ml min-1; 70 mg m-2 at CRCL > 100 ml min-1. PMID- 8431375 TI - Combination or mild single agent chemotherapy for advanced breast cancer? CMF vs epirubicin measuring quality of life. AB - Forty patients with advanced breast cancer, randomised to receive CMF or weekly low dose Epirubicin, were evaluated by UICC criteria of response and WHO toxicity criteria, in addition to three QoL instruments: the 'Qualitator' daily diary card, 4 weekly Nottingham Health Profile (NHP) and Linear Analogue Self Assessment (LASA). Response rates were 58% for CMF and 29% for epirubicin (chi 2 = 3.51, 1 d.f., P > 0.05). Median time to treatment failure was 24 weeks for CMF, 7 weeks for epirubicin (P < 0.05) but survival was similar in both groups. Survival was better for responders than for non-responders (medians 87 and 30 weeks, P = 0.02). CMF caused more objective alopecia (P < 0.001), nausea and vomiting (P < 0.001) and haematological toxicity (P < 0.02). However, QoL measures only recorded a significant difference in energy and pain, influenced primarily by the non-responders in each treatment group but with no difference in overall global scores. Scores for responders, irrespective of treatment, were better to start with (LASA P = 0.001); at 12 weeks, scores had improved (Qualitator P < 0.05; NHP P < 0.05). Scores in non-responders showed no change. In this small study aggressive chemotherapy gave better response and similar survival without impairing Quality of life overall. Detailed QoL measurement should be integral to all cancer chemotherapy trials. PMID- 8431376 TI - High-dose folinic acid with 5-fluorouracil bolus and continuous infusion in the treatment of advanced gastric and oesophageal adenocarcinoma. PMID- 8431377 TI - [Surfactant therapy]. PMID- 8431378 TI - [Education in pediatric nursing at the Leipzig Pediatric hospital]. PMID- 8431379 TI - [Treatment of umbilical hernias]. PMID- 8431380 TI - [Dangerous Salmonellae]. PMID- 8431381 TI - [Improvement of benefits for the family]. PMID- 8431383 TI - [Nursing aspects in caring for injuries]. PMID- 8431382 TI - [150 years Olga Hospital in Stuttgart, the regal pediatric hospital with tradition]. PMID- 8431384 TI - [Inguinal hernia--guideline for care]. PMID- 8431385 TI - [Aspiration of meconium-containing amniotic fluid]. PMID- 8431386 TI - The British Journal of Industrial Medicine: 50 years on. PMID- 8431388 TI - Markers of early renal changes induced by industrial pollutants. II. Application to workers exposed to lead. AB - The present study has been carried out in the framework of a collaborative research project on the development of new markers of nephrotoxicity. A battery of more than 20 potential indicators of renal changes has been applied to 50 workers exposed to lead (Pb) and 50 control subjects. After application of selection criteria 41 exposed and 41 control workers were eventually retained for the final statistical analysis. The average blood Pb concentration of exposed workers was 480 micrograms/l and their mean duration of exposure was 14 years. The battery of tests included parameters capable of detecting functional deficits (for example, urinary proteins of low or high molecular weight), biochemical alterations (for example, urinary eicosanoids, glycosaminoglycans, sialic acid) or cell damage (for example, urinary tubular antigens or enzymes) at different sites of the nephron or the kidney. The most outstanding effect found in workers exposed to Pb was an interference with the renal synthesis of eicosanoids, resulting in lower urinary excretion of 6-keto-PGF1 alpha and an enhanced excretion of thromboxane (TXB2). The health significance of these biochemical alterations, detectable at low exposure to Pb is unknown. As they were not associated with any sign of renal dysfunction, they may represent reversible biochemical effects or only contribute to the degradation of the renal function from the onset of clinical Pb nephropathy. The urinary excretion of some tubular antigens was also positively associated with duration of exposure to Pb. Another effect of Pb that might deserve further study is a significant increase in urinary sialic acid concentration. PMID- 8431387 TI - Markers of early renal changes induced by industrial pollutants. I. Application to workers exposed to mercury vapour. AB - Several markers of renal changes have been measured in a cohort of 50 workers exposed to elemental mercury (Hg) and in 50 control workers. After application of selection criteria 44 exposed and 49 control workers were retained for the final statistical analysis. Exposed workers excreted on average 22 micrograms Hg/g creatinine and their mean duration of exposure was 11 years. Three types of renal markers were studied--namely, functional markers (creatinine and beta 2 microglobulin in serum, urinary proteins of low or high molecular weight); cytotoxicity markers (tubular antigens and enzymes in urine), and biochemical markers (eicosanoids, thromboxane, fibronectin, kallikrein, sialic acid, glycosaminoglycans in urine, red blood cell membrane negative charges). Several bloodborne indicators of polyclonal activation were also measured to test the hypothesis that an immune mechanism might be involved in the renal toxicity of elemental Hg. The main renal changes associated with exposure to Hg were indicative of tubular cytotoxicity (increased leakage of tubular antigens and enzymes in urine) and biochemical alterations (decreased urinary excretion of some eicosanoids and glycosaminoglycans and lowering of urinary pH). The concentrations of anti-DNA antibodies and total immunoglobulin E in serum were also positively associated with the concentration of Hg in urine and in blood respectively. The renal effects were mainly found in workers excreting more than 50 micrograms Hg/g creatinine, which corroborates our previous estimate of the biological threshold of Hg in urine. As these effects, however, were unrelated to the duration of exposure and not accompanied by functional changes (for example, microproteinuria), they may not necessarily represent clinically significant alterations of renal function. PMID- 8431389 TI - Markers of early renal changes induced by industrial pollutants. III. Application to workers exposed to cadmium. AB - Cadmium (Cd) was the third heavy metal investigated in the European collaborative research project on the development and validation of new markers of nephrotoxicity. Fifty workers exposed to Cd and 50 control workers were examined. After application of selection criteria 37 workers (mean age 43) exposed to Cd for an average of 11.3 years; and 43 age matched referents were retained for final analysis. The average concentrations of Cd in blood (Cd-B) and urine (Cd-U) of exposed workers were 5.5 micrograms Cd/l and 5.4 micrograms Cd/g creatinine respectively. By contrast with lead and mercury, Cd had a broad spectrum of effects on the kidney, producing significant alterations in amounts of almost all potential indicators of nephrotoxicity that were measured in urine--namely, low and high molecular weight proteins, kidney derived antigens or enzymes, prostanoids, and various other biochemical indices such as glycosaminoglycans and sialic acid. An increase in beta 2-microglobulin and a decrease of sialic acid concentration were found in serum. Dose-effect/response relations could be established between most of these markers and Cd-U or Cd-B. The thresholds of Cd U associated with a significantly higher probability of change in these indicators were estimated by logistic regression analysis. Three main groups of thresholds could be identified: one around 2 micrograms Cd/g creatinine mainly associated with biochemical alterations, a second around 4 micrograms Cd/g creatinine for high molecular weight proteins and some tubular antigens or enzymes, and a third one around 10 micrograms Cd/g creatinine for low molecular weight proteins and other indicators. The recent recommendation by the American Conference of Governmental Industrial Hygienists (ACGIH) of 5 micrograms Cd/g creatinine in urine as the biological exposure limit for occupational exposure to Cd appears thus justified, although for most of the effects occurring around this threshold the link with the subsequent development of overt Cd nephropathy is not established. In that respect, the very early interference with production of some prostanoids (threshold 2 micrograms Cd/g creatinine) deserves further investigation; although this effect might contribute to protect the filtration capacity of the kidneys, it might also play a part in the toxicity of Cd on bone. PMID- 8431390 TI - Evaluation of delta-aminolaevulinic acid in blood of workers exposed to lead. AB - Exposure-effect and exposure-response relation between exposure to lead and delta aminolaevulinic acid concentration in blood (ALA-B) were examined in 238 male workers exposed to lead. Concentrations of ALA-B ranged from 26 to 352 micrograms/l and lead concentrations in blood (Pb-B) from 7.1 to 86.0 micrograms/dl. Concentrations of ALA-B correlated closely with concentrations of Pb-B (r = 0.74), and increased ALA-B concentration occurred at Pb-B concentrations of around 30 micrograms/dl. Exposure-response curves indicated that the 50 percentile response doses were roughly 30, 40, and 50 micrograms/dl Pb-B when cut off points of ALA-B were set at 50, 60, and 70 micrograms/l respectively. The sensitivity and specificity of measurements of ALA-B concentrations for health screening were sufficiently high when the health based exposure limits of lead were set at 30-50 micrograms/dl. Moreover, a pronounced increase in ALA-B concentrations occurred when the inhibition rate of erythrocyte ALA dehydratase exceeded 85%. These findings suggest that ALA-B is a useful indicator for assessing the early effects of exposure to lead on haem biosynthesis. PMID- 8431391 TI - Donald Hunter 1898-1978: editor BJIM 1944-50. PMID- 8431392 TI - Toxicokinetics of toluene and urinary excretion of hippuric acid after human exposure to 2H8-toluene. AB - Nine male volunteers were exposed to 2H8-toluene (200 mg/m3 for two hours during a workload of 50 W) via inspiratory air with the aid of a breathing valve and mouthpiece. Labelled toluene was used to differentiate between hippuric acid originating from exposure to toluene and hippuric acid normally excreted in urine. The total uptake of toluene was 2.2 (standard deviation (SD) 0.2) mmol, or 50% of the amount inhaled. Four hours after the end of exposure 1.4 (SD 0.3) mmol or 65% of the total uptake had been excreted in urine as 2H-hippuric acid and 20 hours after the end of exposure the cumulative excretion of 2H-hippuric acid was 1.8 (SD 0.3) mmol, or 78% of the total uptake. By contrast the cumulative excretion of labelled plus unlabelled hippuric acid exceeded the total uptake of toluene already after four hours. The excretion rate of 2H-hippuric acid was highest, about 5 mumol/min, during exposure and the SD between the subjects was low. The background concentrations of unlabelled hippuric acid in urine were high, however, and there were large differences between subjects. These findings confirm earlier indications that for low exposure, urinary hippuric acid concentration cannot be used for biological monitoring of exposure to toluene. PMID- 8431393 TI - Asthma, rhinitis, and dermatitis in workers exposed to reactive dyes. AB - A survey was conducted at 15 textile plants with dyehouses in western Sweden. Employees with a history of work related rhinitis, asthma, or skin symptoms were offered a clinical and immunological investigation including skin prick tests, skin patch tests, and radioallergosorbent tests (RASTs) to detect specific allergy to reactive dyes. Among the 1142 employees, 162 were exposed to reactive dyes and 10 of these (6%) reported work related respiratory or nasal symptoms. An allergy to reactive dyes could be confirmed in five (3%, 95% confidence interval 1-7%). All but one had been exposed to reactive dyes for one year or less before the onset of symptoms. Positive RASTs could be detected in four of the five patients. All of the RAST positive patients were positive to remazol black B, but six out of eight additional remazol dyes also elicited positive results. RAST and RAST inhibition showed a cross reactivity between some of the dyes. Seven persons with work related dermatitis and three with urticaria or Quincke oedema were found. In one patient contact dermatitis to a monoazo dye was shown, but no positive patch test reactions to reactive dyes. IgE-mediated allergy to reactive dyes seems to be an important cause of respiratory and nasal symptoms among dyehouse employees exposed to dust from reactive dyes. PMID- 8431394 TI - Exposure to ethylene glycol ethers and spermatogenic disorders in man: a case control study. AB - A case-control study was conducted among first time patients at a clinic for reproductive disorders. The study group consisted of 1019 cases, defined as patients diagnosed infertile or subfertile on the basis of a spermiogram and 475 controls who were diagnosed as normally fertile by the same procedure. Possible exposure to ethylene glycol ethers was assessed by the presence of the urinary metabolites methoxyacetic acid (MAA) and ethoxyacetic acid (EAA) respectively for 2-methoxyethanol and 2-ethoxyethanol or their acetates. In total, EAA was detected in 39 cases and six controls, with a highly significant odds ratio of 3.11 (p = 0.004). On the other hand, MAA was only found in one case and two controls. The presence of EAA in urine proved to be strongly associated with exposure to preparations containing solvents, especially paint products, and with some groups of occupations, the most important of which were also directly or possibly connected with paint products. The absence of a significant correlation between the concentration of urinary EAA and the various measures of sperm quality could be explained by the expected latent period between exposure and observed effects. Other temporal aspects of the relation between exposure as judged from the presence of urinary EAA and diagnosis are also discussed. PMID- 8431396 TI - Chronic carbon tetrachloride intoxication. 1944. PMID- 8431395 TI - non-Hodgkin's lymphoma and occupation in Sweden: a registry based analysis. AB - Incidence of non-Hodgkin's lymphoma in different employment categories was evaluated from the Swedish Cancer-Environment Registry, which links cancer incidence during 1961 to 1979 with occupational information from the 1960 census. New associations were found for men employed in shoemaking and shoe repair, porcelain and earthenware industries, education, and other white collar occupations. Several findings supported associations found in other countries, including excesses among woodworkers, furniture makers, electric power plant workers, farmers, dairy workers, lorry drivers, and other land transport workers. Risks were not increased among chemists, chemical or rubber manufacturing workers, or petrochemical refinery workers. Caution must be used in drawing causal inferences from these linked registry data because information on exposure and duration of employment is not available. Nevertheless, this study has suggested new clues to possible occupational determinants of non-Hodgkin's lymphoma. PMID- 8431397 TI - Incidence of lung cancer by histological type among asbestos cement workers in Denmark. AB - OBJECTIVE: A significant twofold increased risk of lung cancer was found among 8000 men employed in the Danish asbestos cement industry between 1928 and 1984. The histological pattern of 104 lung cancer cases was studied with the aim of evaluating a relation between specific morphological types, duration of employment, and time since first employment. METHODS: Age, sex, and calendar time specific incidence of morphological subtypes of lung cancer (adenocarcinoma, squamous cell carcinoma, anaplastic carcinoma, and unspecified malignant tumour) for all Danish men were computed from 1943 to 1984, from data routinely collected by the Danish Cancer Registry. Person-years of observation were counted from 15 years after the date of first employment until date of diagnosis of cancer, death, emigration, or the end of follow up on 31 December 1984. Expected numbers of cases were computed by applying person-years at risk to the appropriate incidence rates. Observed numbers were distributed accordingly and the relative risk calculated. RESULTS: The relative risk for adenocarcinoma was 3.31 (observed (O) 24, expected (E) 7.26), for squamous cell carcinoma 1.67 (O, 37, E, 22.12), for anaplastic carcinoma 1.58 (O, 23, E, 14.53), and for unspecified malignant tumour 1.57 (O, 18, E, 11.46). An increased risk by duration of employment and time since first employment was most pronounced for adenocarcinoma. CONCLUSION: The link between adenocarcinoma and asbestos was confirmed in this, the first study of risk of lung cancer by histological category based on incident cancer cases for a whole population during a 50 year period. PMID- 8431398 TI - Asbestos and cancer: history and public policy. PMID- 8431399 TI - Immunohistochemical alterations after muscle trauma. AB - The proteins fibrin, fibrinogen, fibronectin and complement C5b-9 were investigated in mechanically damaged skeletal muscle. An accumulation of fibrin, fibrinogen and fibronectin could be observed immediately after intra-vital trauma in damaged fibre zones, later an accumulation at the torn edges of the fibres. The accumulation of complement C5b-9 began one hour after trauma. After post mortem trauma no positive reactions could be observed for any of the proteins. The degree of expression of these proteins can therefore be used to differentiate between vital and postmortem muscle damage as well as the estimation of wound age in the early antemortem time period. PMID- 8431400 TI - ABO blood grouping of bloodstains by sandwich ELISA using monoclonal antibody specific for human red cell band 3. AB - ABO blood grouping of human bloodstains was performed by a sandwich ELISA using a species-specific monoclonal antibody to the amino-terminal cytoplasmic domain of human red cell membrane band 3. In a blind trial, all A, B and O bloodstains (a 1 cm long thread) and AB bloodstains (a 1.5 cm long thread) were accurately typed by this method. Even when bloodstains were contaminated by other body fluids (e.g., semen and saliva), only the ABO blood group epitopes on band 3 of the red cell membrane were detected. Thus, identification of human blood and ABO blood grouping of bloodstains which were contaminated by other body fluids could be simultaneously performed by this method. PMID- 8431401 TI - Sex determination of forensic samples: co-amplification and simultaneous detection of a Y-specific and an X-specific DNA sequence. AB - The detection of restriction fragment length polymorphisms (RFLP) (1) in DNA extracted from forensic samples remains impossible in a significant number of cases due to deterioration and contamination of the biological material and the extremely low quantities of DNA isolated. The polymerase chain reaction (PCR) is a recent and particularly convenient method for analysing and typing very small amounts (10-20 ng) of degraded human DNA. DNA analysis at the level of a few cells present in forensic samples such as bloodstains, semen stains, vaginal swabs and head hair bulbs now appears possible using DNA amplification. A PCR protocol was adapted to simultaneously amplify a Y-specific DNA repeat sequence from the DYZ1 locus and an X-specific DNA repeat sequence from the DXS424 locus. The co-amplified Y-specific DNA fragment (102 bp) and X-specific DNA fragments (181-199 bp) were visualized on an ethidium bromide-stained 4% agarose gel. The male or female type of the amplified DNA extracted from blood samples, bloodstains, semen stains, vaginal swabs, brain tissue and 1, 2, 5, or 10 head hair bulbs was determined. PMID- 8431402 TI - The immunohistochemical localization of alpha 1-antichymotrypsin and fibronectin and its meaning for the determination of the vitality of human skin wounds. AB - A total of 39 vital human skin wounds (20 cases with short survival times ranging from a few seconds to approximately 30 min and 19 cases with wound ages between 50 min and 13 days) were investigated. Alpha 1-antichymotrypsin (A1-ACT) was visualized by immunohistochemistry. Additionally, fibronectin was localized in 13 of these wounds (8 cases with short and 5 cases with longer survival times). Furthermore, 13 postmortem lesions (stab wounds) were removed from corpses approximately 4 h after infliction and analyzed for A1-ACT and fibronectin. The "vital" reaction previously described for A1-ACT in form of a band-shaped staining pattern at the wound edges was observed in both vital wounds and in most postmortem lesions. A similar reaction was also obtained for fibronectin in wounds inflicted after death, but could be unambiguously distinguished from vital fibronectin staining by morphological criteria. Therefore, it seems questionable that the vitality of skin wounds can be determined by the immunohistochemical detection of A1-ACT and probably other proteinase inhibitors. The meaning of the localization of fibronectin for the determination of the vitality of human skin wounds with a survival time of at least a few minutes could be confirmed. PMID- 8431403 TI - Population data of the HLA DQ alpha locus in Dutch Caucasians. Comparison with other population studies. AB - The HLA DQ alpha amplification and typing kit has been designed to be used by the forensic community for purposes of identity testing. The introduction of any new DNA marker in forensic identity testing requires the establishment of a population database for the relevant population(s). To this end allele and genotype frequencies for the HLA DQ alpha locus were determined in a Dutch Caucasian population sample and compared with 7 other population genetic studies. In our population sample the HLA DQ alpha genotype frequencies did not deviate from Hardy-Weinberg expectations and for this locus the power of discrimination is 0.94. A test for homogeneity of the HLA DQ alpha population data based on the allele frequency counts for 8 Caucasian population samples was performed and significant differences were found (P = 0.007). The differences in the frequency of the HLA DQ alpha 2 and 3 alleles are the major cause of this deviation. No deviation from population homogeneity was observed when we compared the genotype frequency distributions among the 8 Caucasian population samples. Combined with the extensive validation studies from Comey and Budowle and Helmuth et al. this population genetic study will allow HLA DQ alpha typing to be used in forensic identity testing in the Netherlands. PMID- 8431404 TI - Postmortem concentrations of thiopental in tissues: a sudden death case. AB - High-performance liquid chromatography was employed to determine the concentration of thiopental in body fluids and tissues in an individual who had died due to intravenous injection of the clinical dose. The blood concentration of thiopental was 0.6 mg/l. Among the 10 tissues examined, the brain and thymus showed the highest level of the drug; 11.9 mg/kg and 7.66 mg/kg, respectively. The results are discussed in the light of the relevant literature. PMID- 8431406 TI - Survival in the market place. PMID- 8431405 TI - Cerebral intraventricular haemorrhage in a young adult. AB - A case of a 26-year-old man who suffered a fatal intraventricular cerebral haemorrhage following an episode of trauma is described. The initial appearance at necropsy suggested a traumatic subarachnoid haemorrhage and initial investigation was directed towards the anterior neck structures and the vertebral arteries with negative results. Dissection of the fixed brain showed a massive intraventricular bleed with secondary involvement of the subarachnoid space and dissection into the cerebral parenchyma. No bleeding points or natural disease of the cerebral vessels could be identified. The practical aspects of diagnosis and the cautious approach necessary in interpreting subarachnoid bleeding is emphasised. The significance of intraventricular haemorrhage following trauma has become more apparent with the advent of computed tomographic scanning. The implications for this and similar cases are considered. PMID- 8431407 TI - Temporomandibular joint synovial fluid analysis. AB - A method for the estimation of the synovial fluid volume of the temporomandibular joint (TMJ) is described. Patients are administered 1.2 g of aspirin and the concentration of salicylate in plasma and in saline aspirates of the TMJ is measured by a sensitive high performance liquid chromatography assay. The ratio of the concentration of salicylate in the saline aspirate to that in the plasma allows the volume of the synovial fluid to be calculated. The method would also allow the determination of the concentration and the absolute amount of putative mediators of pathology in the upper joint. PMID- 8431408 TI - Temporalis haemangioma presenting as temporomandibular joint pain dysfunction syndrome. AB - Pathology within the infratemporal and temporal fossa is notoriously difficult to diagnose. A rare case of a haemangioma within the temporalis muscle, originally diagnosed as temporomandibular joint dysfunction, illustrates the difficulty of recognising disease within this region when clinical signs are minimal. PMID- 8431409 TI - Mandibular fractures in northern Finland in the 1980s--a 10-year study. AB - A total of 317 mandibular fracture patients treated and diagnosed at the Oulu University Hospital and at the Department of Oral and Maxillofacial Surgery, University of Oulu, Finland, between 1981 and 1990 were analyzed from patient files and radiographs. The mean number of mandibular fracture patients per year was 31.7 (range 21 and 45) and the mean age of the patients 31.3 years (range 4 78 years). The female:male ratio was 1:3.1. There seemed to be a tendency for decrease in the proportion of violence and traffic accidents as causes of mandibular fractures toward the end of the period concerned, reflecting partly the influence of mandatory use of safety belts and partly that the hospital in the northernmost part of Finland, where the consumption of alcohol is higher than in the province of Oulu, could treat all mandibular fractures itself during the last year studied thus decreasing the injuries caused by violence at the Oulu University Hospital. It was also noted that fewer fractures were caused at weekends than on weekdays during the latter years of the decade and that the proportion of male victims decreased except for the last year examined, 1990. PMID- 8431410 TI - Midazolam and somatosensory evoked potentials. AB - The effect of intravenous midazolam on the somatosensory evoked potentials (SEP's) elicited from median nerve stimulation was investigated in a study on 20 volunteers. SEP's were recorded from contralateral scalp before and at 5, 30, and 60 min after drug administration. Relative amplitudes of the early components (N18-N20) were essentially stable, while relative amplitudes of the late components (N50-P90, P90-N160, N160-P250 and P250-N380) were reduced significantly after midazolam administration and had not returned to baseline 60 min after administration. Given the correlation between late SEP amplitude and subjective reports of experimental pain, the data support the possibility that administration of midazolam in conscious sedation doses may have some effect on pain in addition to its better documented sedative and amnesic properties. PMID- 8431411 TI - Short-term outcome of arthroscopic surgery of temporomandibular joint osteoarthrosis and internal derangement: a randomized controlled clinical trial. AB - Various types of treatment have been proposed for patients with temporomandibular joint (TMJ) osteoarthrosis and internal derangement. We examined the suitability of several assessment instruments developed in previous investigations for treatment-evaluation in a clinical trial comparing arthroscopic surgery with non surgical treatment for a specific subgroup of TMJ osteoarthrosis and internal derangement, characterized by joint pain and restricted mobility. Twenty-one patients appeared to obey strict criteria for participation, and were randomly assigned to receive arthroscopic surgery followed by post-operative physical therapy (n = 9), or non-surgical treatment (n = 12). Individual outcome was assessed immediately following treatment and after 6 months based on a priori defined criteria. Patients treated with arthroscopic surgery reported more pain relief and more improvement of mobility than patients treated non-surgically, although clinical assessment results were comparable between the two groups. No major changes were observed regarding general well-being and interference with daily activities. The results of this pilot study indicate that the assessment methods are sufficiently sensitive for changes in pain, mobility, and functional ability. Despite the higher degree of subjective pain relief and appreciation of improvement of mobility in the arthroscopic surgery group, with these more formal assessment instruments this difference could not be confirmed. It is concluded that the preliminary results should be verified in a larger trial with a slightly adjusted design. PMID- 8431412 TI - Neurilemmoma of the head and neck. AB - The neurilemmoma is an uncommon tumour of the oral cavity. In this present series of soft tissue neurilemmomas the majority occurred within or around the mouth. Initially these were provisionally diagnosed on clinical appearances and behaviour as commoner benign lesions, including the fibro-epithelial polyp, mucocele and papilloma. On sampling they were found to have the histological features of a neurilemmoma. This suggests that the solitary neurilemmoma occurs more frequently than previously reported and should be included in the differential diagnosis of these more frequent benign lesions occurring in and around the mouth. PMID- 8431413 TI - Orofacial myiasis. AB - Oral myiasis is rare, particularly in western developed countries. This case report describes the presentation of oral myiasis as an enlarged submandibular lymph node associated with a buccal mass, in a Caucasian male who had recently returned from the Gambia. It highlights the need for increased clinical awareness when dealing with patients who have recently travelled overseas. PMID- 8431414 TI - Extraparotid Warthin's tumours--report of 10 cases. AB - In the period 1970-1990, 10 cases of extraparotid Warthin's tumours were registered at the Free University Hospital in Amsterdam, The Netherlands. In view of the relatively rare occurrence of these lesions, the clinical data of the patients are reported, together with a discussion on the somewhat controversial subject of extraparotid Warthin's tumours. PMID- 8431415 TI - Ewing's sarcoma of the mandible: a case report. AB - The authors report the case of an 8-year-old boy with a Ewing's sarcoma localized to the mandible. The therapeutic modalities consisting of induction chemotherapy, surgical removal of the involved portion of the mandible with reconstruction using a parascapular osteo-cutaneous free flap, and maintenance chemotherapy are described. Emphasis is placed on the importance of performing a wide resection and the use of a multidisciplinary team approach in the treatment of these unusual tumours. PMID- 8431416 TI - Evaluation of a swan's neck osteotome for pterygomaxillary dysjunction in the Le Fort I osteotomy. AB - The incidence of pterygoid plate fractures resulting from pterygomaxillary dysjunction with a swan's neck osteotome has been determined in a study on cadavers. Fractures did occur at the level of the osteotomy cut but were less frequent than found in a previous study using a conventional curved pterygoid chisel. PMID- 8431417 TI - Citation for the presentation of the 1991 Down Surgical Prize to Derek Henderson. PMID- 8431418 TI - p53 expression in oral disease. PMID- 8431419 TI - Mannitol-specific enzyme II of the phosphoenolpyruvate-dependent phosphotransferase system of Escherichia coli: physical size of enzyme IImtl and its domains IIBA and IIC in the active state. AB - The size of enzyme IImtl solubilized in the active state has been determined by size-exclusion chromatography under conditions that favor the association of the enzyme. The contribution of the detergent bound to the enzyme was determined by solubilizing the enzyme and running the TSK250 column in a number of detergents with decreasing micellar sizes. The size, expressed as the equivalent molecular mass of a globular protein, decreased from 315 kDa in decylPEG, to 275 kDa in octylPEG and octyl glucoside, and then to 245 kDa in cholate. Enzyme IImtl is not active in the latter three detergents when at concentrations above their cmc values but still binds mannitol with high affinity without significant loss of sites. This, together with the full reversibility of the inactivation, is taken as evidence that the enzyme does not unfold or dissociate in these detergents. The sizes of the separated domains IIBA and IIC of enzyme IImtl were 38 and 175 kDa, respectively. The cytoplasmic domain, IIBA, was monomeric at high concentration, whereas the membrane-bound domain, IIC, was associated at much lower concentration. Apparently, the sites that interact to keep enzyme IImtl in the associated state are exclusively located in the membrane-bound domain. PMID- 8431420 TI - Molecular cloning of testicular 20 alpha-hydroxysteroid dehydrogenase: identity with aldose reductase. AB - Complementary DNA (cDNA) clones encoding bovine testicular 20 alpha hydroxysteroid dehydrogenase (20 alpha-HSD) have been isolated from a bovine testicular lambda gt11 library using polyclonal antibodies against 20 alpha-HSD and DNA probe hybridization. Nucleotide sequencing of three independently isolated clones was used to establish a composite cDNA sequence that encodes the enzyme. It contains a coding sequence of 921 nucleotides, a stop codon, and a 264 nucleotide 3'-noncoding segment which allowed deduction of the amino acid sequence of the enzyme. A computer homology search of the 20 alpha-HSD cDNA performed against the GenBank DNA sequence database revealed it to be identical with bovine lens aldose reductase (alditol:NADPH oxidoreductase; EC 1.1.1.21), and a literature search reveals the deduced amino acid sequence to be identical with that reported for the bovine enzyme. Sequences obtained from the N-terminus of purified testicular 20 alpha-HSD and from random peptides obtained by treatment with endopeptidase Lys-C are all identical with regions of the deduced amino acid sequence of 20 alpha-HSD and/or the published sequence of aldose reductase. Further, the enzyme purified to homogeneity by following activity with 17-hydroxyprogesterone as a substrate was shown to reduce glucose, glyceraldehyde, and benzaldehyde (all classic aldose reductase substrates). Finally, 17-hydroxyprogesterone inhibited the reduction of benzaldehyde and glyceraldehyde. Because aldose reductase has been implicated in the etiology of diabetic complications, acceptance of steroid substrates may offer new implications for therapy. PMID- 8431421 TI - Hevein: NMR assignment and assessment of solution-state folding for the agglutinin-toxin motif. AB - The first high-resolution solution-state structure of a member of the toxin agglutinin folding motif with the WGA disulfide linkage is presented. The 1H NMR spectrum of hevein has been 100% assigned from residue 2 through residue 43, the C-terminus, using two-dimensional correlation and NOE spectroscopy. During the course of the NOESY analysis, the three-dimensional structural features of hevein were derived, using nonstereospecific distance constraints (with tight bounds) for XPLOR simulated annealing followed by unconstrained relaxation in the CHARMm force field, at two levels of long-range constraint density. In addition, a large number of low-bound-only constraints, corresponding to unobserved NOE's, were used in both refinements. The first structure elucidation employed a total of 180 distance constraints (60 of which were medium or long range, i/i+n with n < or = 2). The second refinement employed 244 (101 medium or long range) constraints: some conformation-insensitive intraresidue constraints were deleted, two misassigned long-range constraints were corrected, and 41 new i/i+n (n > or = 2) constraints were added. The average bounds precisions of the two refinements were comparable (+/- 0.44 A) and significantly tighter than those that result when a universal low bound corresponding to the sum of the van der Waals radii was used. (The more conservative treatment of NOE's gave the same final structure but required a higher constraint density before assignment errors would stand out during the refinement.) Constraint density also has a significant influence on convergence and accuracy using tight constraints. The study demonstrates that convergence within an ensemble of solution structures is not a dependable criterion for either the accuracy or precision of the derived structure. The best fitting conformers from the refinement at the higher constraint density bear a greater similarity to the solid-state structure of the domains of wheat germ agglutinin (0.95 A rmsd over residues 2-32) than to the recently reported 2.8-A X ray structure of hevein (1.25 A rmsd over residues 2-32, 2.83 A rmsd over residues 2-42). The consensus conformer from the solution data is defined to a backbone rmsd of < 0.6 A over the full sequence for which NMR data could be collected.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8431422 TI - Aromatic-histidine interactions in the zinc finger motif: structural inequivalence of phenylalanine and tyrosine in the hydrophobic core. AB - The classical Zn finger (Cys-X2,4-Cys-X3-Phe-X5-Leu-X2-His-X3,4-His contains [corrected] an aromatic-histidine interaction (underlined) in its hydrophobic core whose importance is suggested by the marked destabilization of a Phe-->Leu analogue [Mortishire-Smith, R.J., Lee, M.S., Bolinger, L., & Wright, P.E. (1992) FEBS Lett. 1, 11-15]. In some Zn finger sequences the central Phe is replaced [corrected] by Tyr, and when present, this substitution is generally conserved among species. To investigate whether Tyr would participate in an analogous aromatic-histidine interaction, we have determined the solution structure in a Phe-->Tyr mutant domain. Its global fold (the beta beta alpha motif) is similar to that of the Phe domain. Although the variant Tyr maintains edge-to-face packing against the proximal histidine, the phenolic ring is displaced toward solvent. Such displacement increases the solvent accessibility of the Tyr p-OH group and reduces steric overlap (and possible electrostatic repulsion) between the Tyr O zeta and His pi electrons. The Tyr analogue exhibits reduced dynamic stability (as indicated by more rapid exchange of amide protons in D2O) and may alternate in rapid equilibrium between major and minor conformers. Inequivalent Tyr-His and Phe-His interactions are likely to be general features of Zn finger architecture. Molecular modeling based on the Zif268 cocrystal structure [Pavletich, N.P., & Pabo, C.O. (1991) Science 252, 809-817] suggests that the variant Tyr p-OH group may readily be positioned to contribute a novel hydrogen bond to a DNA phosphate. PMID- 8431423 TI - Dynamics of a monomeric insulin analogue: testing the molten-globule hypothesis. AB - The structure of insulin exhibits local and nonlocal differences among crystal forms and so provides an important model for analysis of protein dynamics. A novel combination of order and disorder has recently been inferred from 2D-NMR studies of the monomeric analogue des-pentapeptide(B26-B30) insulin (DPI) under acidic conditions [the molten-globule hypothesis; Hua, Q.X., Kochoyan, M., & Weiss, M.A. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 2379-2383]. Distance geometry structures are similar in general to crystal structures but differ by rigid-body displacements of alpha-helices; the hydrophobic core is not well ordered due to insufficient long-range restraints. To test whether such informational uncertainty may represent physical disorder, we have performed complementary studies of the thermal unfolding of DPI and its interaction with 1 anilino-8-naphthalenesulfonate (ANS). Experimental design is based on a predicted analogy between DPI and A-state models of protein-folding intermediates (the "molten globule"). Unfolding is monitored by five distinct biophysical probes: photochemical dynamic nuclear polarization (photo-CIDNP), differential scanning calorimetry (DSC), circular dichroism (CD), 1H-NMR chemical shifts, and slowly exchanging amide 1H-NMR resonances in D2O solution. The results provide evidence that DPI adopts a compact partially folded state. Because the 2D-NMR spectrum of an engineered insulin monomer under physiological conditions is similar to that of DPI under acidic conditions [Weiss, M.A., Hua, Q.X., Frank, B.H., Lynch, C., & Shoelson, S.E. (1991) Biochemistry 30, 7373-7389], we propose that the functional form of insulin is a molten globule. PMID- 8431424 TI - Molecular dynamics simulation of HIV-1 protease in a crystalline environment and in solution. AB - Simulations of the unbound form of the human immunodeficiency virus type 1 protease have been carried out to 200 ps in a crystalline environment and in solution. Solution simulations were performed with and without charge-balancing counterions. The results are compared with the 2.8-A crystallographic structure of Wlodawer et al. [(1989) Science 245, 616], and a proposed model for the solution structure which involves local refolding of the flap regions is presented. The simulations suggest the crystal packing environment of the protease dimer stabilizes the flaps in an extended conformation. Solvation of the dimer leads to local refolding of the flaps which contract toward the active site, forming increased overlap and stronger intersubunit hydrogn bonding at the tips. The degree to which the flaps overlap in solution is observed to depend on the charge state of the system. PMID- 8431425 TI - Further characterization of the psbH locus of Synechocystis sp. PCC 6803: inactivation of psbH impairs QA to QB electron transport in photosystem 2. AB - The psbH gene encodes a small protein which copurifies with photosystem 2. In the cyanobacterium Synechocystis sp. PCC 6803, psbH is located upstream of the cytochrome b6-f complex genes petC and petA. In striking contrast, in the genomes of plant chloroplasts, psbH is cotranscribed with petB and petD, encoding the other two major subunits of the cytochrome b6-f complex. We report that in Synechocystis sp. PCC 6803 monocistronic psbH and dicistronic petCA transcripts are probably initiated separately, each from DNA regions bearing some similarity to Escherichia coli sigma 70 promoters. Synechocystis sp. PCC 6803 psbH null mutants were generated by cartridge mutagenesis. Studies using a rapid screening procedure involving in situ complementation showed that the PsbH protein is not absolutely required for the assembly of a functionally active photosystem 2 complex since psbH insertion and deletion strains were able to grow photoautotrophically. The rate of photoautotrophic growth was, however, slower than the wild type, and studies of oxygen evolution, chlorophyll fluorescence, and thermoluminescence indicated that this reduction in growth rate is probably due mainly to an impairment in electron flow from QA to QB. We conclude, therefore, that the PsbH protein is not an absolute requirement for photosystem 2 activity but that it functions to optimize electron flow between the two secondary plastoquinone acceptors by interacting with the QB site on the D1 protein. PMID- 8431426 TI - Lysine 258 in aspartate aminotransferase: enforcer of the Circe effect for amino acid substrates and general-base catalyst for the 1,3-prototropic shift. AB - The replacement of Lys258 by alanine (K258A) in aspartate aminotransferase reduces the rate constant for the central, 1,3-prototropic shift by 10(6)-10(8) fold, confirming the role of Lys258 as the general-base catalyst for this step. The rate constant for the 1,3-prototropic shift interconverting K258A aldimine and ketimine intermediates is pH-independent like that of the wild-type enzyme (WT-AATase). K258A binds amino acid substrates in external aldimine intermediates 10(5)-fold more tightly than does WT-AATase. The excess amino acid binding energy observed in the mutant is sacrificed by the WT-AATase in order to increase the value of kcat. The net result is that the kcat/KM values for amino acid substrates are reduced only 3-100-fold by the mutation. This provides a clear example of the Circe effect propounded by Jencks [Jencks, W. P. (1975) Adv. Enzymol. Rel. Areas Mol. Biol. 43, 219]. Part of the increase in kcat due to the inclusion of Lys258 is accomplished by a 10(4)-10(5)-fold acceleration of external aldimine formation and hydrolysis. This step is partially rate determining for K258A, but not for WT-AATase. A significant consequence of the utilization of amino acid binding energy for catalysis is the raising of the dissociation constants for these substrates to levels near the physiological concentrations of amino acids. The major product of the reaction of K258A with oxalacetate is pyruvate due to decarboxylation of the beta-imine formed in the ketimine intermediate. PMID- 8431427 TI - Continuous-wave quantum yields of various cobalamins are influenced by competition between geminate recombination and cage escape. AB - Quantum yields of photolysis of the cobalt-carbon bond for three cobalamin compounds were measured with a continuous-wave laser at 442 nm under both aerobic and anaerobic conditions. Aerobically, the initial homolysis product, Co(II) cobalamin, is trapped by oxygen to form aquocobalamin. Use of an excess of the radical trapping reagent 2,2,6,6-tetramethyl-1-piperidinyloxyl, under anaerobic conditions, scavenges the carbon radical and allows detection of the cobalt(II) photoproduct. Quantum yields measured under anaerobic conditions for 5' deoxyadenosylcobalamin (phi (Co-C alpha),442 = 0.20 +/- 0.03) and methylcobalamin (phi (Co-C alpha),442 = 0.35 +/- 0.03) are in agreement with the values obtained under aerobic conditions (phi (Co-C alpha),442 = 0.19 +/- 0.04 and phi (Co-C alpha),442 = 0.36 +/- 0.04, respectively). Additionally, the quantum yield values for 5'-deoxyadenosylcobalamin and its base-off derivative (phi (Co-C alpha),442 = 0.045 +/- 0.015) match those obtained on a nanosecond time scale [Chen, E., & Chance, M. R. (1990) J. Biol. Chem. 256, 12987-12994]. A comparison of quantum yields obtained anaerobically for 5'-deoxyadenosylcobalamin and methylcobalamin in H2O versus ethylene glycol shows a 4-fold decrease for the former cobalamin and no change for the latter. These quantum yields are evaluated in terms of time independent radical separation distances. PMID- 8431428 TI - Halothane metabolism: the dihydrolipoamide acetyltransferase subunit of the pyruvate dehydrogenase complex molecularly mimics trifluoroacetyl-protein adducts. AB - Monospecific antibodies (anti-CF3CO antibodies), directed against trifluoroacetyl protein adducts (CF3CO-protein adducts) that are elicited in tissues of experimental animals and humans upon exposure to the anesthetic agent halothane, recognize cross-reactive proteins of 64 and 52 kDa in several tissues of rats and the liver of humans not previously exposed to the drug. These cross-reactive proteins mimic CF3CO-protein adducts. Here, by the use of the anti-CF3CO antibody as an immunoaffinity matrix, the protein of 64 kDa was purified from rat heart microsomal fractions. The amino acid sequence of six internal tryptic peptides exhibited 100% identity with the corresponding deduced amino acid sequences of the dihydrolipoamide acetyltransferase component (E2 subunit) of the rat liver pyruvate dehydrogenase (PDH) complex, as encoded by the cDNA clone pRMIT [Gershwin, M. E., Mackay, I. R., Sturgess, A., & Coppel, R. L. (1987) J. Immunol. 138, 3525-3531]. Lipoic acid, the prosthetic group of the E2 subunit of the PDH complex, exhibited immunochemical properties very similar to those of the hapten derivative N6-trifluoroacetyl-L-lysine (CF3CO-Lys). On immunoblots, free lipoic acid inhibited the recognition of the E2 subunit, of the not yet identified protein of 52 kDa, and of the bulk of CF3CO-protein adducts by anti-CF3CO antibody with half-maximal inhibitory constants of 0.05, 10.0, and 8.5 mM, respectively. Lipoic acid also abolished the precipitation of the native E2 subunit by anti-CF3CO antibody from solubilized rat heart mitochondrial fractions. These data suggest that lipoic acid is involved in the molecular mimicry of CF3CO-protein adduct-related epitopes by the E2 subunit of the PDH complex. PMID- 8431429 TI - Kinetic evaluation of substrate-dependent origin of the lag phase in soybean lipoxygenase-1 catalyzed reactions. AB - We have measured, under identical conditions, the time courses for the native lipoxygenase (Fe2+ form)-catalyzed conversion of linoleic acid into 13 hydroperoxy-9,11-octadecadienoic acid (HPOD) and the oxidation of the Fe2+ form of enzyme to the Fe3+ form (in 0.1 M borate buffer, pH 10.0, at 25 degrees C) using a stopped-flow spectrophoto/fluorometer. The experimental results clearly demonstrate that the time course for the appearance of the reaction product is much shorter than that for the conversion of E-Fe2+ to E-Fe3+; the latter process involves a pronounced lag phase whereas the former does not. This suggests that the Fe2+ form of the enzyme is also catalytically active and that the origin of the lag phase is not intrinsic to the oxidation of the enzyme bound iron cofactor. When the Fe3+ form of the enzyme is utilized to investigate the time course of product formation, the lag phase was observed at substrate concentrations higher than 20 microM. The magnitude of this lag phase increases with the increases with the increase in the initial concentration of the substrate (at least up to the range where substrate is not dimerized) and decreases in the presence of increasing concentrations of HPOD (exogenously added to the reaction mixture). No lag phase is evident at substrate concentrations in the range of 10 microM or less. We have examined the effects of varied concentrations of substrate and product on the initial rates of the lipoxygenase catalyzed reaction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431430 TI - Engineering the zinc binding site of human carbonic anhydrase II: structure of the His-94-->Cys apoenzyme in a new crystalline form. AB - The structure of the His-94-->Cys variant of human carbonic anhydrase II (CAII) has been determined by X-ray crystallographic methods to a resolution of 2.3 A with a final crystallographic R factor of 0.155. This variant of CAII crystallizes in orthorhombic space group P2(1)2(1)2(1) which is the first example of a new crystal form for this important zinc hydrase (the wild-type enzyme crystallizes in monoclinic space group P21 under similar crystallization conditions). Although the overall structure of the enzyme in the orthorhombic crystal form is similar to that of the wild-type protein in the monoclinic crystal form, the rms deviation of C alpha atoms between the two structures is 0.5 A. Larger structural deviations occur in regions of the protein molecule involved in crystal lattice contacts, and significant structural changes are found in the polypeptide strand containing Cys-94. Surprisingly, no electron density corresponding to a zinc ion is found in the active site of crystalline His-94-->Cys CAII, even though the stoichiometry of zinc binding to this variant in solution is confirmed by atomic absorption spectroscopy. However, the KD for zinc dissociation from the variant is increased 10(4)-fold compared with wild type enzyme; furthermore, under the crystallization conditions of high ionic strength (1.75-2.5 M ammonium sulfate), the observed KD is increased further, which leads to zinc dissociation. Spectroscopic analysis of Co(2+)-substituted His-94-->Cys CAII indicates that the metal binds in a tetrahedral geometry with a new thiolate bond.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431431 TI - Protein glycation by ADP-ribose: studies of model conjugates. AB - Protein glycation by hexoses has been implicated in the pathophysiology of a number of diseases as well as the aging process. Studies of ADP-ribose polymer metabolism have shown that free ADP-ribose is generated at high rates in the cell nucleus following DNA damage. Protein glycation by ADP-ribose has been reported although the chemistry is not understood. Described here is the synthesis and characterization of model conjugates for protein glycation of lysine residues by ADP-ribose. Two stable conjugates derived from ADP-ribose and n-butylamine were isolated and characterized. Both conjugates were shown to be ketoamines derived from a Schiff base by an Amadori rearrangement. The chemical stability of the ketamines allowed them to be differentiated from all classes of enzymic protein modification by ADP-ribose. Further, their chemical properties suggest that a previous report of histone H1 modification in carcinogen treated cells was due to glycation by ADP-ribose. PMID- 8431432 TI - Adenosylcobinamide methyl phosphate as a pseudocoenzyme for diol dehydrase. AB - Adenosylcobinamide methyl phosphate, a novel analog of adenosylcobalamin lacking the nucleotide loop moiety, was synthesized. It did not show detectable coenzymic activity but behaved as a strong competitive inhibitor against AdoCbl with relatively high affinity (Ki = 2.5 microM). When apoenzyme was incubated at 37 degrees C with this analog in the presence of substrate, the Co-C bond of the analog was almost completely and irreversibly cleaved within 10 min, forming an enzyme-bound Co(II)-containing species. The cleavage was not observed in the absence of substrate. The Co-C bond cleavage in the presence of substrate was not catalytic but stoichiometric, implying that the Co-C bond of the analog undergoes activation when the analog binds to the active site of the enzyme. 5' Deoxyadenosine was the only product derived from the adenosyl group of the analog upon the Co-C bond cleavage. Apoenzyme did not undergo modification during this process. Therefore, it seems likely that adenosylcobinamide methyl phosphate acts as a pseudocoenzyme or a potent suicide coenzyme. Since adenosylcobinamide neither functions as coenzyme nor binds tightly to apoenzyme, it can be concluded that the phosphodiester moiety of the nucleotide loop of adenosylcobalamin is essential for tight binding to apoenzyme and therefore for subsequent activation of the Co-C bond and catalysis. It is also evident that the nucleotide loop is obligatory for the normal progress of catalytic cycle. PMID- 8431433 TI - Human nucleotide excision nuclease incises synthetic double-stranded DNA containing a pyrimidine dimer at the fourth phosphodiester linkage 3' to the pyrimidine dimer. AB - Linear 75mer double-stranded DNA containing a single pyrimidine dimer at a unique site was used to investigate pyrimidine dimer-dependent endonuclease activities from human cells. HeLaS3 cell extract incised the target DNA at the fourth phosphodiester linkage 3' to the pyrimidine dimer. However, incision of the DNA at 5' side of the pyrimidine dimer was not detected. The incision was also detected in cell extracts prepared from other excision repair-proficient cell lines. Incision was detected only on the DNA strand containing a pyrimidine dimer in the presence of poly(dI-dC)-poly(dI- dC) double strand. The reaction required Mg2+ but not ATP. The extract prepared from excision repair-deficient xeroderma pigmentosum (XP) cells belonging to the complementation group A was unable to incise the DNA. Extracts from the complementation groups C, D, and G incised the DNA very weakly at the third phosphodiester linkage 3' to the pyrimidine dimer, a site different from that incised by normal human cell extract. These results suggest that the observed incision reaction is associated with excision repair in human cells. PMID- 8431434 TI - Use of adenosine (5')polyphospho(5')pyridoxals to study the substrate-binding region of glutathione synthetase from Escherichia coli B. AB - Adenosine(5')polyphospho(5')pyridoxals (APn-PLs, n = 2, 3, 4) were examined for affinity labeling of glutathione synthetase (EC 6.3.2.3) from Escherichia coli B. When the enzyme was incubated with an APn-PL or pyridoxal phosphate in the presence of Mg2+ and then reduced with sodium borohydride, it was most rapidly inactivated by AP4-PL. AP4-PL had a high affinity to the enzyme. The dissociation constant of AP4-PL in the inactivation process was 23 microM. The enzyme was almost completely protected from inactivation by addition of either ATP or gamma glutamylcysteine. Complete inactivation corresponded to the incorporation of 1 mol of AP4-PL/mol of subunit of the tetrameric enzyme. Proteolytic digestion and sequence analysis of the AP4-PL-labeled enzyme revealed that only Lys-18 was modified. In contrast, the less efficient AP3-PL was found attached to Lys-17, Lys-18, Lys-144, and Lys-148. In the three-dimensional structure of the enzyme, Lys-18 is located close to the putative gamma-glutamylcysteine-binding site, but Lys-17, Lys-144, and Lys-148 are in the mouth of the inner-solvent region, at the bottom of which is the active-site cleft. Furthermore, difference Fourier analysis with the AP4-PL-soaked crystal of the enzyme showed that the adenosine moiety of the bound AP4-PL was in the crevice, which is the ATP-binding site of the enzyme. These results demonstrate the bivalent binding of AP4-PL lying across the gamma-glutamylcysteine- and ATP-binding sites. PMID- 8431435 TI - Evidence for a self-associating equilibrium intermediate during folding of human growth hormone. AB - It has been previously shown, by equilibrium denaturation, that human growth hormone (hGH) folds by a cooperative two-state process. This is in contrast to the folding pathways of other nonhuman growth hormones that contain stable monomeric and multimeric equilibrium intermediates. We have reinvestigated the equilibrium denaturation of hGH at higher protein concentrations and found smooth transitions from the native to denatured state, but the calculated free energy for unfolding, delta G, decreases with increasing protein concentration. The effect of protein concentration on the delta G of unfolding is due to the presence of folding intermediates that have a tendency to self-associate. A correlation was found between the equilibrium denaturation data and the observation of precipitation that occurs upon refolding, suggesting that the presence of self-associated folding intermediates leads to precipitation. Direct evidence for the existence of a soluble, associated intermediate was obtained by dynamic light scattering (DLS) and equilibrium analytical ultracentrifugation. Peptide fragments from the third helix of either hGH or bovine growth hormone (bGH) were capable of inhibiting the formation of this aggregated species and prevent precipitation during refolding. The data show that the folding pathway of hGH is similar to that of nonhuman growth hormones except for differences in the tendency for intermediates to self-associate. These findings are relevant to the design and interpretation of equilibrium folding experiments, and may be important to understanding mechanistic details of protein folding and aggregation in vivo. PMID- 8431436 TI - Evidence for the presence of five distinct proteolytic components in the pituitary multicatalytic proteinase complex. Properties of two components cleaving bonds on the carboxyl side of branched chain and small neutral amino acids. AB - Initial studies on the specificity of the multicatalytic proteinase complex (MPC; EC 3.4.99.46) led to the identification of three distinct proteolytic components designated as trypsin-like, chymotrypsin-like, and peptidylglutamyl-peptide hydrolyzing, all sensitive to inactivation by 3,4-dichloroisocoumarin (DCI), a general serine proteinase inhibitor. The three components cleave the peptidyl arylamide bonds in the model synthetic substrates, Z-(D)-Ala-Leu-Arg-2 naphthylamide, Z-Gly-Gly-Leu-p-nitroanilide, and Z-Leu-Leu-Glu-2-naphthylamide, respectively. We report here evidence for the presence in the MPC of two additional distinct components, neither of them capable of cleaving the three model substrates. One of these components cleaves the Leu-Gly and the Leu-Ala bonds in the substrates Cbz-Gly-Pro-Ala-Leu-Gly-p-aminobenzoate and Cbz-Gly-Pro Ala-Leu-Ala-p-aminobenzoate, respectively, and is activated by treatment of the MPC with DCI, N-ethylmaleimide, Mg2+, Ca2+, and low concentrations of sodium dodecyl sulfate and fatty acids. This component is apparently identical with the previously identified DCI-resistant component of the MPC that cleaves preferentially bonds on the carboxyl side of branched chain amino acids in natural peptides including neurotensin and proinsulin [Cardozo, C., Vinitsky, A., Hidalgo, M. C., Michaud, C., & Orlowski, M. (1992) Biochemistry 31, 7373-7380]. It is probably also identical with the component proposed to be the main factor responsible for the caseinolytic activity [Pereira, M. E., Nguyen, T., Wagner, B. J., Margolis, J. W., Yu, B., & Wilk, S. (1992a) J. Biol. Chem. 267, 7949-7955]. The designation "branched chain amino acid preferring" (BrAAP) is proposed for this component. The second component cleaves peptide bonds between the small neutral amino acids Ala-Gly and Gly-Gly in the substrates Cbz-Gly-Pro-Ala-Ala-Gly p-aminobenzoate and Cbz-Gly-Pro-Ala-Gly-Gly-p-aminobenzoate, respectively. This component is sensitive to inactivation by DCI, N-ethylmaleimide, and organic mercurials, but unlike the BrAAP it is significantly activated neither by Mg2+ or Ca2+ nor by fatty acids or sodium dodecyl sulfate. The designation "small neutral amino acid preferring" (SNAAP) is proposed for this component. Both components are sensitive to inhibition by the peptidyl-aldehydes N-acetyl-Leu-Leu norleucinal (Ac-LLnL-CHO; calpain inhibitor I) and N-acetyl-Leu-Leu-methioninal (Ac-LLM-CHO; calpain inhibitor II) but are resistant to inhibition by Z-LLF-CHO, a potent inhibitor of the chymotrypsin-like activity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8431437 TI - Stability analysis of latent and active 72-kDa type IV collagenase: the role of tissue inhibitor of metalloproteinases-2 (TIMP-2). AB - The degradation of extracellular matrix is an important facet of many physiological and pathological processes. The collagenases form a family of matrix degradative enzymes that have similar active site sequences and activation mechanisms and are inhibited by a specific class of proteinase inhibitors referred to as tissue inhibitors of metalloproteinases. Regulation of enzyme activity is a complex process involving control at multiple levels: message transcription and translation, activation of latent proenzymes, inhibition of activity by specific inhibitors, and degradation of activated enzymes. We have examined the role of the proteinase inhibitor tissue inhibitor of metalloproteinases-2 (TIMP-2) on two of these processes: the autoactivation and autodegradation of the human 72-kDa type IV collagenase. We compared the stability of the enzyme in these two processes using three different enzyme preparations: the enzyme-inhibitor complex as isolated from human A2058 melanoma cells, recombinant enzyme free of TIMP-2, and enzyme separated from TIMP-2 by acid denaturation. We have found little evidence to support the hypothesis that the enzyme is able to autoactive, as no autoactivation occurs in the presence of TIMP-2 and only 20% autoactivation occurs in its absence, and then only after 24 h of incubation at 37 degrees C. However, TIMP-2 does appear to inhibit autodegradation, possibly by a mechanism distinct from its ability to inhibit substrate proteolysis. Enzyme isolated via chromatography involving acid mobile phases produces a mixture of cleavage products that is mostly denatured, inactive enzyme fragments. The role of TIMP-2 as an inhibitor of autodegradation suggests that the enzyme may show two physiological phenotypes: the free enzyme having a high level of activity and rapid autodegradation and enzyme-inhibitor complex having a low level of activity resistant to autodegradation. PMID- 8431438 TI - Effects of phosphatidylcholine fatty acyl chain length on calcium binding and other functions of the (Ca(2+)-Mg2+)-ATPase. AB - The ATPase activity of the (Ca(2+)-Mg2+)-ATPase purified from skeletal muscle sarcoplasmic reticulum and reconstituted into phosphatidylcholine bilayers of defined composition depends on the fatty acyl chain length of the surrounding phospholipid. The stoichiometry of Ca2+ binding to the ATPase is also sensitive to fatty acyl chain length, changing from the normal two Ca2+ ions bound per ATPase molecule to one Ca2+ ion bound for the ATPase reconstituted with phosphatidylcholines of chain lengths C12, C14, or C24. For the ATPase reconstituted with mixture of phosphatidylcholines where one phosphatidylcholine supports a Ca2+ binding stoichiometry of two and the other a stoichiometry of one, a highly cooperative change in binding stoichiometry with change in phospholipid composition is observed, suggesting that the effects of phospholipids follow from binding to a large number of sites at the lipid-protein interface of the ATPase. For the ATPase reconstituted with either 1-myristoyl-2 oleoylphosphatidylcholine or 1-oleoyl-2-myristoylphosphatidylcholine, the stoichiometry of Ca2+ binding is the normal two per ATPase molecule. Effects of short-chain phosphatidylcholines on Ca2+ binding stoichiometry and on ATPase activity can be reversed by addition of androstenol, oleic acid, methyl oleate, or oleyl alcohol but these molecules have no effect on the ATPase reconstituted with dinervonylphosphatidylcholine (C24:1). For the ATPase reconstituted with phosphatidylcholines with chain lengths between C16 and C22, release of the two bound Ca2+ ions is sequential, with release of the second Ca2+ being inhibited by high concentrations of Ca2+ in the bathing medium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431439 TI - Magnesium in the active site of Escherichia coli alkaline phosphatase is important for both structural stabilization and catalysis. AB - Site-specific mutagenesis was used to explore the roles of the side chains of residues Lys-328 and Asp-153 in Escherichia coli alkaline phosphatase. The D153H enzyme exhibits a 3.5-fold decrease in activity at pH 8.0 compared to that of the wild-type enzyme, while a double mutant D153H/K328H exhibits a 16-fold decrease in activity under these conditions. However, the Km values for both enzymes, employing the substrate p-nitrophenyl phosphate, are lower than the value for the wild-type enzyme. The Ki for phosphate, which is pH- and Mg(2+)-dependent, is decreased for the D153H enzyme and increased for the D153H/K328H enzyme. Relative to the wild-type enzyme, both mutant enzymes bind Mg2+ more weakly and undergo a time-dependent activation induced by Mg2+. The half-time of the activation process is independent of the Mg2+ concentration, indicating that the activation most probably involves a conformational change. The pH versus activity profiles of both enzymes are altered relative to that of the wild-type enzyme and exhibit greatly enhanced activity, relative to that of the wild-type enzyme, at high pH values. The pre-steady-state kinetics for the D153H and D153H/K328H enzymes exhibit a transient burst of product formation at pH 8.0, under conditions at which the wild-type enzyme exhibits no transient burst, indicating that at pH 8.0 the hydrolysis of the covalent enzyme-phosphate complex is rate-determining and not the release of phosphate from the noncovalent enzyme-phosphate complex as is observed for the wild-type enzyme. Therefore, these mutations are directly influencing catalysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431440 TI - Defining the precision with which a protein structure is determined by NMR. Application to motilin. AB - A simple procedure is introduced for accurately defining the precision with which the Cartesian coordinates of any macromolecular structure are determined by nuclear Overhauser data. The method utilizes an ensemble of structures obtained from an array of independent simulated data sets derived from a final structure. Using the noise-free, back-calculated NOE spectrum as the "true" NOE spectrum, simulated Monte Carlo data sets are created by superimposing onto the "true" spectrum Gaussian distributed noise with a standard deviation equal to that of the residuals. Full relaxation matrix refinements of the simulated data sets provide probability distributions of the Cartesian coordinates for each atom in the model. Molecular dynamics simulations are included to estimate the effect of sparse information on the precision. The procedure is applied here to the 22 residue peptide hormone motilin, and the results are compared to those obtained using the conventional method of analyzing multiple refinements using a single distance constraint set. The average root mean square deviation for alpha-carbon atoms in the central portion (Arg12-Arg18) of the single helix of motilin was determined to be 0.72 A by the Monte Carlo method, compared to 1.3 A determined by an analysis of the 10 best DIANA structures using the same number of constraints between the same atoms. The origin of the bias of the conventional method is discussed. PMID- 8431441 TI - Refined structure for the complex of 1-deoxynojirimycin with glucoamylase from Aspergillus awamori var. X100 to 2.4-A resolution. AB - The three-dimensional structure of the complex of 1-deoxynojirimycin with glucoamylase II-(471) from Aspergillus awamori var. X100 has been determined to 2.4-A resolution. The model includes residues corresponding to residues 1-471 of glucoamylase I from Aspergillus niger, two molecules of bound 1-deoxynojirimycin and 605 sites for water molecules. The crystallographic R factor from refinement is 0.119, and the root-mean-squared deviation in bond distances is 0.012 A. The inhibitor complex confirms the location of the active site in the packing void of the alpha/alpha-barrel as proposed by Aleshin et al. [Aleshin, A., Golubev, A., Firsov, L., & Honzatko, R. B. (1992) J. Biol. Chem. 267, 19291-19298]. One inhibitor molecule is associated with strong electron density and represents the principal site of interaction of 1-deoxynojirimycin with the enzyme. The other 1 deoxynojirimycin molecule is associated with weak electron density and therefore, probably represents a binding site of low affinity. Interactions of 1 deoxynojirimycin with the enzyme at its principal site involve Arg 45, Asp 55, Arg 305, and carbonyl 177. In addition, a water molecule (water 500) hydrogen bonds to Glu 400 and the 6-hydroxyl of 1-deoxynojirimycin and is at an approximate distance of 3.3 A from the "anomeric" carbon of the inhibitor. The structural arrangement of functional groups near the inhibitor molecule suggests that Glu 179 is a catalytic acid, Glu 400 a catalytic base, and water 500 the attacking nucleophile in the hydrolysis of maltooligosaccharides. The relevance of the X-ray work to proposed mechanisms of enzymatic hydrolysis of oligosaccharides is discussed. PMID- 8431442 TI - Evidence for protonation in the human neutrophil formyl peptide receptor binding pocket. AB - We have studied the interaction of a family of fluorescent formyl peptides with their receptor using spectrofluorometric and flow cytometric methods. The peptides contained four (CHO-Met-Leu-Phe-Lys-fluorescein), five (CHO-Met-Leu-Phe Phe-Lys-fluorescein), or six (CHO-Nle-Leu-Phe-Nle-Tyr-Lys- fluorescein) amino acids. As observed in earlier studies, the fluorescent peptides containing four and five amino acids were quenched upon binding to the receptor, while the hexapeptide was not. While the degree of quenching of the bound tetrapeptide was largely unchanged, the quenching of the bound pentapeptide decreased with increasing pH over the range of pH 6.5-9.0. Ligand binding studies have shown that the mole fraction of tetrapeptide or pentapeptide bound in kinetic analysis markedly decreased with increasing pH as a consequence of increasing ligand dissociation rate constant. The dependence of the binding parameters for the hexapeptide on pH was much less pronounced. Over a pH range from pH 7.3 to 9.0, the hexapeptide showed little change in binding affinity, while the tetrapeptide and pentapeptide increased in Kd approximately 2.0- and 2.5-fold, respectively. These results indicate that the formyl peptide receptor binding pocket contains at least two microenvironments. The pH sensitivity of the pentapeptide quenching is consistent with a protonating environment, while the pH-independent quenching of the tetrapeptide may reflect aromatic stacking or a hydrophobic microenvironment. The pH-dependent ligand dissociation also suggests that the protonation in the pocket stabilizes ligand binding, which may indicate an alteration in the binding pocket structure. Protonation or hydrogen bonding of the pentapeptide may lead to even further stabilization of that ligand. PMID- 8431443 TI - Calcium binding and translocation properties of glucagon and its fragments. AB - Earlier studies have indicated that the N- and C-terminal regions of glucagon are functionally and structurally different. We have sought to understand this distinction in terms of the interaction of glucagon and its N- and C-terminal fragments with Ca2+, Mg2+, and Zn2+ in a nonpolar milieu. CD spectral data, in 98% (v/v) trifluoroethanol in water, reveal two binding sites for Ca2+ and Mg2+ and one site for Zn2+ in the intact hormone as well as in the C-terminal 19-29 fragment. The 1-6 fragment did not bind Zn2+ and formed a 2:1 peptide-Ca2+ or Mg2+ complex. With glucagon and the 19-29 fragment, cation binding caused changes in the peptide's helix content. Fluorescence spectral changes involving Trp-25 in the 19-29 fragment and Trp-25 and Tyr-10 and/or Tyr-13 in glucagon were seen on Ca2+ binding to one of the two sites, while Zn2+ binding produced no change in fluorescence. The spectral data suggest that Ca2+ and Zn2+ binding sites (with Kd in the micromolar range in 98% trifluoroethanol) are distinct and are contained in the C-terminal domain of glucagon. Glucagon and the 19-29 fragment, but not the 1-6 fragment, caused an influx of Ca2+ (as monitored by spectral changes in arsenazo III) in unilamellar vesicles made of dimyristoyllecithin. Leakage of vesicle contents induced by the 19-29 fragment was minimal but was significant (approximately 10%) in the case of glucagon. The transport data suggest an interaction of the C-terminal domain of glucagon with Ca2+ at the lipid-water interface.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431444 TI - Assembly of fibronectin molecules with mutations or deletions of the carboxyl terminal type I modules. AB - Fibronectin is a large modular protein that is assembled into fibrils in a stepwise process that involves the binding of soluble fibronectin to the cell surface and formation of fibronectin multimers that are stabilized by disulfides. Fibronectin contains two types of disulfide-containing repeat modules, types I and II. The type I modules form units that mediate binding to assembly sites (I-1 through I-5), mediate binding to gelatin (I-6 through I-9 plus the type II modules), or have no known function other than fibrin binding (I-10 through I 12). All type I modules contain four cysteines that are disulfide-linked in a 1 3, 2-4 arrangement, except for I-12 that contains six cysteines disulfide-bonded in an unknown arrangement. I-12 contains the consensus sequence Cys-Xaa-Yaa-Cys found in a number of proteins involved in disulfide exchange reactions [Holmgren, A. (1985) Annu. Rev. Biochem. 54, 237; Boniface, J. J., & Reichert, L. E., Jr. (1990) Science 247, 61]. We explored the role of I-12 and adjacent type I modules of fibronectin in matrix assembly. We generated mutant fibronectins in which the second and sixth or fifth and sixth cysteine residues in I-12 were changed to serines (CS mutants) or that contained deletions of the 12th (delta 12) or 10th through 12th (delta 10-12) type I modules. Expression of I-12 as a fusion protein with the gelatin binding part of fibronectin indicated that this module folds independently and that the most likely disulfide pairing is 1-4, 2-6, 3 5.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431445 TI - Transitional steps in the solubilization of protein-containing membranes and liposomes by nonionic detergent. AB - Membrane solubilization by dodecyl maltoside was studied, using Ca(2+)-ATPase membranes and liposome preparations as prototypes of biological membranes. In equilibrium dialysis experiments, transition from saturable incorporation of monomeric detergent into the membrane to cooperative binding already occurred at a free detergent concentration about 50% of the cmc. This transition was discontinuous for unilamellar liposomes of dioleoylphosphatidylcholine, but gradual for Ca(2+)-ATPase membranes and multilayered liposomes of sarcoplasmic reticulum lipid. Equilibrium detergent binding by Ca(2+)-ATPase membranes (expressed on the basis of lipid content) was the same as for detergent binding by multilamellar liposomes of sarcoplasmic reticulum lipid. Equilibration involving cooperative binding was considerably delayed (for many days) if detergent was presented gradually to the membranous preparations in nonmicellar form by diffusion across the dialysis membrane, while equilibration of detergent occurred rapidly if detergent in micellar form was added directly to the membrane preparations. In contrast, equilibration was rapid in both directions if detergent was added at levels below that required to initiate cooperative binding. Detergent interaction resulted in a biphasic decrease in light scattering of Ca(2+)-ATPase membranes. The first of these decreases coincided with the onset of cooperative binding, while the second one was associated with a decreased sedimentability during ultracentrifugation, i.e., with usual criteria of solubilization. The concentration at which this occurred corresponded to the level of free detergent at which lipid, after detergent solubilization, segregated from detergent after gel chromatography.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431446 TI - Purification and characterization of a human protein that binds to damaged DNA. AB - Xeroderma pigmentosum (XP) is an inherited disease characterized by defective repair of DNA damaged by ultraviolet (UV) radiation or agents that produce bulky DNA adducts. Human cells contain a factor that is deficient in a subset of patients from XP complementation group E and binds to DNA damaged by UV, cisplatin, or denaturation. This factor, XPE binding factor (XPE-BF), was purified to near homogeneity. The denatured protein migrated as a 125-kDa polypeptide on SDS-PAGE, and the native protein migrated primarily as a monomer on gel filtration and glycerol gradient sedimentation. Sedimentation revealed major peak in binding activity at 6.8 S, corresponding to the monomeric form, and a minor peak at 14.5 S, suggesting a homodimeric form. Binding activity was dependent on unmodified cysteine residues, stimulated by magnesium, and inhibited by zinc. Binding to UV-damaged nucleotides was 500,000-fold greater than for intact nucleotides, explaining how a molecule with an abundance of only 1-2 molecules per megabase can survey the genome for damaged DNA. Binding required a minimal DNA substrate of between 16 and 26 bp, as determined by a novel "shoe size" assay. Consistent with its previously noted versatility, XPE-BF bound to some cyclobutane pyrimidine dimers and at least one other UV-induced lesion. However, it may not bind to a subset of cyclobutane dimers, likely including the thymine dimer. These findings may explain the relatively mild phenotype of XP group E and suggest the existence of at least one other binding protein involved in the XP repair pathway. PMID- 8431447 TI - The antitumor drug nogalamycin forms two different intercalation complexes with d(GCGT).d(ACGC). AB - The structures of the physical complex of d(GCGT).d(ACGC) with the anthracycline antitumor drug nogalamycin were studied in order to determine the sequence specificity and the drug orientation at the symmetric d(C2G3).d(C6G7) binding site of this oligonucleotide. For this purpose, one- and two-dimensional NMR techniques were used in combination with molecular mechanics and molecular dynamics computations. Analysis of the NMR spectra reveals that nogalamycin forms two different intercalation complexes with d(GCGT).d(ACGC). These complexes are called complex I and complex II and are present in a ratio of 0.45:0.55. In both complexes the nogalamycin is intercalated at the d(C2G3).d(C6G7) sequence with the bicyclic and nogalose sugars residing in the major and minor groove, respectively. This results in a buckling of the flanking base pairs and a doubling of the inter-base-pair distances at the intercalation site. In complex I, the aglycon ring of the drug stacks with the C6-G7 bases, and the sugars are directed to the G1.C8 end; while in the case of complex II the anthraquinone ring system is stacked with C2-G3 bases, and the sugars are pointed to the T4.A5 base pair end. The two nogalamycin-d(GCGT).d(ACGC) structures are stabilized by intra- and intermolecular hydrogen bonds, electrostatic interactions, and van der Waals contacts. Comparison of different nogalamycin-oligonucleotide structures reveals a nogalamycin binding specificity to the 3'-side of the cytosine base in cytosine purine sequences in double-stranded DNA. PMID- 8431448 TI - Specific glycosaminoglycans support the inhibition of thrombin by plasminogen activator inhibitor 1. AB - In the absence of accessory components, plasminogen activator inhibitor 1 (PAI-1) rapidly forms equimolar, inactive complexes both with tissue-type (t-PA) and with urokinase-type (u-PA) plamsinogen activator. In the presence of either the glycoprotein vitronectin or the glycosaminoglycan heparin, PAI-1 is endowed with additional, efficient thrombin-inhibitory properties (Ehrlich et al., 1990, 1991a). Here, we have investigated the interaction between PAI-1, thrombin, and glycosaminoglycans in more detail. Inhibition of thrombin by PAI-1 was quantitatively analyzed in the presence of a wide range of concentrations of heparin, heparan sulfate, dermatan sulfate, chondroitin 4-sulfate, chondroitin 6 sulfate, keratan sulfate, and hyaluronic acid by measuring residual amidolytic activity. In addition, a qualitative analysis was performed by determining the formation of SDS-stable, equimolar complexes between thrombin and PAI-1 in the presence of various glycosaminoglycans. Heparin, at concentrations between 0.1 and 1 microgram/mL, significantly promoted thrombin inhibition by PAI-1 as well as SDS-stable complex formation. Suboptimal inhibition was observed with dermatan sulfate, chondroitin 4-sulfate, and heparan sulfate at concentrations that are at least 1 order of magnitude higher than that required for optimal inhibition in the presence of heparin. Virtually no inhibition of thrombin and SDS-stable complex formation was detected with any of the other glycosaminoglycans at concentrations between 0.1 and 1 microgram/mL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431449 TI - Role of phosphate in Fe2+ binding to horse spleen holoferritin. AB - In order to identify the function and location of phosphate associated with the iron core of horse spleen ferritin (HoSF), the phosphate content of native HoSF was altered by two procedures. Adjustment of pH from 7.0 to 10.0 irreversibly released 53% of the phosphate and 10% of the iron, while lowering the pH to 5.0 reversibly released 43% of the phosphate and 35% of the iron. Reversible release of 85% of the initial phosphate (but little iron release) also occurs upon reduction with methyl viologen (MV) or dithionite. Most of the phosphate is released in the early stages of reduction of the iron core, suggesting that the phosphate resides primarily on the mineral core surface. Reduction followed by chelation altered both the iron and phosphate content of the HoSF mineral cores. HoSF iron cores first reconstituted in the absence of phosphate and then incubated with added phosphate did not bind phosphate. However, when HoSF was first reconstituted in the absence of phosphate and then equilibrated anaerobically with both Fe2+ and phosphate, then phosphate was incorporated in amounts similar to native HoSF. Fe2+ binding to native, phosphate altered, and reconstituted HoSF in the presence and absence of phosphate clearly showed that Fe2+ binding to the mineral core depends on the presence of core-bound phosphate. Fe2+ binding to phosphate-depleted mineral cores or to cores reconstituted with 621, 2158, and 3013 Fe/HoSF core in the absence of phosphate bound only eight Fe2+ per entire ferritin molecule, clearly showing that Fe2+ has no measurable affinity for the phosphate-free, reconstituted mineral core.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431450 TI - Characterization of the hydrophobic interaction of steroids with endoplasmic reticulum membranes by quenching of 6,8(14)-bis-dehydro-17 alpha hydroxyprogesterone fluorescence. AB - The fluorescence behaviour of 4,6,8(14)-trien-3-one steroids, which exhibit fluorescence in protic media but no fluorescence in hydrophobic environments, was used to characterize the molecular nature and temperature-sensitivity of steroid hormone-biomembrane interactions. Since 17 alpha-hydroxyprogesterone as the key intermediate is known to accumulate in smooth endoplasmic reticulum membranes in the course of adrenal and testicular steroid hormone biosynthesis, its fluorescent analogue, 6,8(14)-bis-dehydro-17 alpha-hydroxyprogesterone (BDHP), was used as the probe molecule. With rat testis microsomal membranes and liposomes, fluorescence quenching in the presence of membranes (related to fluorescence in aqueous solution) was independent on steroid concentration but was dependent on membrane lipid concentration in terms of a hyperbolic function. Complete fluorescence loss occurred at infinite lipid concentration at 20 degrees C, indicating complete insertion of the steroid probe into the hydrophobic portion of the membrane compartment. The partition coefficient KP increased with increasing temperature as a consequence of increased membrane fluidity. The result that BDHP fluorescence decreased considerably with elevated temperature in both the aqueous and the membrane milieu was interpreted as the consequence of increasing molecular mobility; this effect was much more pronounced in the aqueous than in the membrane environment. On the basis of local BDHP concentrations within the membrane phase (calculated from KP), relative fluorescence quenching was over-proportional at low temperatures; under that condition, hydrophobic interactions with rigid membrane lipid domains are obviously favoured. PMID- 8431451 TI - Characterization of the membrane-associating domain of the sperm adhesive protein, bindin. AB - Bindin is an adhesive protein that mediates the binding of sea urchin sperm to the egg during fertilization. Bindin selectively associates with gel-phase phospholipid vesicles in a peripheral fashion. Bindin interacts specifically with sulfated fucan on the egg's surface, and directly with the phospholipid bilayer of the sperm. Analysis of a series of deletion mutants of recombinant bindin was undertaken to define the membrane associating domain of bindin. Recombinant and sperm bindin display nearly identical binding kinetics to gel-phase phospholipids and have equivalent saturation points of approx. 250 lipid molecules per molecule of bindin. Deletion mutants of bindin which contain residues 75-130 retained specific membrane binding activity. Synthetic peptides corresponding to residues 69-130, and 92-130 also display gel-phase specific membrane association. This region is highly conserved within four different species of bindin molecules. Circular dichroism spectroscopy of synthetic peptides corresponding to residues 92-130 and 69-130 suggests that a distinct change in conformation takes place upon binding liposomes. Taken together, these data indicate that the membrane binding activity of bindin residues within this highly conserved region of the bindin molecule. PMID- 8431452 TI - Effects of alkaline pH on the stimulation of glucose transport in rat skeletal muscle. AB - Alkaline pH has been reported to cause release of Ca2+ from skeletal muscle sarcoplasmic reticulum (SR). Elevation of sarcoplasmic Ca2+ concentration is thought to stimulate glucose transport in skeletal muscle. In this context, we examined the effect of alkaline pH (extracellular pH of 8.6) on 3-O-methylglucose transport in skeletal muscle. Incubation of rat epitrochlearis muscles at pH 8.6 for 45 min resulted in an approx. 3-fold increase in glucose transport activity, which was not affected by reducing Ca2+ concentration in the incubation medium and essentially completely blocked by 25 microM dantrolene, an inhibitor of SR Ca2+ release. In addition to stimulating glucose transport by itself, alkaline pH may partially inhibit the stimulation of sugar transport by insulin hypoxia and contractions, as the combined effect of alkaline pH and the maximal effect of insulin, contractions, or hypoxia on glucose transport are not different from the maximal effects of insulin, hypoxia, or contractions alone. The maximal effects of insulin and contractions, and of insulin and hypoxia, on glucose transport are normally additive in muscle. Alkaline pH completely prevented this additivity. In summary, our results show that alkaline pH stimulates glucose transport activity in skeletal muscle and provide evidence suggesting that this effect is mediated by Ca2+. They further show that alkaline pH blocks the additivity of the maximal effects of insulin and contractions or hypoxia suggesting that alkaline pH may partially inhibit the stimulation of glucose transport by insulin, contraction and hypoxia. PMID- 8431453 TI - Purification of a basic fibroblast growth factor-binding proteoglycan from bovine cardiac plasma membrane. AB - A heparan sulfate proteoglycan (HSPG) from bovine cardiac plasma membrane was purified to homogeneity using either isoelectric focusing or anion-exchange chromatography, followed by affinity chromatography on immobilized basic fibroblast growth factor (bFGF). Fractions were assayed for bFGF-binding activity using 125I-bFGF as a probe. Purified proteoglycan ran as a broad band on SDS PAGE, spanning an apparent molecular mass range of 100-200 kDa, and could be incorporated into liposomes. Digestion of radioiodinated proteoglycan with heparitinase yielded a product of 73 kDa, while digestion with chondroitinase ABC did not change the apparent molecular mass. Monoclonal antibody directed against the ectodomain of another plasma membrane HSPG, syndecan, failed to recognize the purified cardiac proteoglycan on immunoblots. We conclude that adult bovine myocardium contains a membrane-associated bFGF-binding heparan sulfate proteoglycan containing little or no chondroitin sulfate and that this HSPG may be distinct from those of the syndecan family of heparan sulfate proteoglycans. PMID- 8431454 TI - Modulation of the synthesis and glycosylation of the glucose transporter protein by transforming growth factor-beta 1 in Swiss 3T3 fibroblasts. AB - Transforming growth factor-beta 1 (TGF-beta 1) stimulated growth and glucose uptake in Swiss mouse fibroblasts. DNA synthesis was increased 2-3-fold after 48 h incubation of growing 3T3 cells with TGF-beta 1 in calf serum-containing medium. Glucose transport activity in the cells was increased within 3 h after addition of TGF-beta 1 and this stimulation continued during incubation for 48 h. TGF-beta 1 also increased the levels of a brain type-glucose transporter (GLUT1) mRNA and the GLUT1 protein (55 kDa) in the membranes, consistent with the increase in glucose uptake. Furthermore, a longer exposure of TGF-beta 1 for 24 48 h induced a marked increase in the 65 kDa GLUT1 in 3T3 cell membranes. Other growth factors such as epidermal growth factor, fibroblast growth factor, transforming growth factor-alpha, and insulin did not elevate glucose uptake and the levels of 55 and 65 kDa GLUT1 proteins. Adding tunicamycin or deoxymannojirimycin to the TGF-beta 1-treated and untreated cells caused these 55 and 65 kDa glucose transporters to migrate as one band at 40-43 kDa. In addition, treating membrane proteins with glycopeptidase F, which removes N-linked oligosaccharides, also generated a glucose transporter of 40 kDa, suggesting that the 55 and 65 kDa GLUT1 proteins have a similar or identical core polypeptide but with different N-linked oligosaccharides. These results indicate that TGF-beta 1 modulates the synthesis of GLUT1 protein as well as its glycosylation in Swiss 3T3 cells, and that these changes may contribute to the control of cell proliferation by TGF-beta 1. PMID- 8431455 TI - Peptide hormone-membrane interactions. Intervesicular transfer of lipophilic gastrin derivatives to artificial membranes and their bioactivities. AB - Incorporation of di-fatty acylglycerol moieties at the N-terminus of human little gastrin-(2-17) leads to self-aggregation of the resulting lipo-gastrins into stable, most probably fluid vesicles. Net intervesicular transfer of the lipo gastrins to phosphatidyl-choline model bilayers occurs at high rates whereby the chain length of the gastrin lipid moiety was found to affect the transfer rate more decisively than the nature of the acceptor vesicle. Similarly, the bioactivity of the lipo-gastrins is again affected by the nature of the lipid moiety suggesting differentiated interdigitation with the natural bilayer components and thus, different two-dimensional migration rates to the target receptors. Embedment of the lipo-gastrins in phosphatidylcholine bilayers at high lipid/gastrin ratios as mimicry of the cell membrane bound state does not result in onset of ordered structure, but leads to full exposure of the gastrin in essentially randomly coiled form at the water/lipid interface. This may result from the artificial N-terminal anchorage of the gastrin molecules to the bilayers, but also from the relatively tight packing of the phosphatidylcholine vesicles. Nevertheless, this observation might suggest that in the present case membrane-induced conformation and orientation may not represent a pre-requisite for the hormone receptor binding process. However, the results of this study clearly confirm even for the non-amphiphilic hormone gastrin a membrane-bound pathway for receptor recognition and occupancy. PMID- 8431456 TI - Oxidation/isomerization of 5-cholesten-3 beta-ol and 5-cholesten-3-one to 4 cholesten-3-one in pure sterol and mixed phospholipid-containing monolayers by cholesterol oxidase. AB - In this study we have examined the cholesterol oxidase (Streptomyces cinnamomeus) catalyzed conversion of either 5-cholesten-3 beta-ol or 5-cholesten-3-one into 4 cholesten-3-one in pure sterol or mixed phospholipid-containing monolayers at the air/buffer interface. The mean molecular area requirement of 5-cholesten-3-one in a pure monolayer was slightly smaller than the comparable area required by 5 cholesten-3 beta-ol (although the collapse pressure was markedly lower for 5 cholesten-3-one), and both sterols were about equally capable of condensing the lateral packing density of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine at a lateral surface pressure of 20 mN/m. Both sterols were converted by cholesterol oxidase to 4-cholesten-3-one, the reaction being faster with 5-cholesten-3-one as compared to 5-cholesten-3-beta-ol. When the temperature-dependency of the cholesterol oxidase catalyzed conversion of the sterols to 4-cholesten-3-one was examined, the Arrhenius activation energy was calculated to +30 kJ/mol and +27 kJ/mol for 5-cholesten-3 beta-ol and 5-cholesten-3-one, respectively, when the sterols were presented to the enzyme as pure sterol monolayers at a lateral surface pressure of 20 mN/m. With a mixed monolayer containing 40 mol% sterol and 60 mol% EPC, the corresponding activation energies were +107 kJ/mol and +96 kJ/mol for 5-cholesten-3 beta-ol and 5-cholesten-3-one, respectively. With the monolayer system used, it appeared that the over all rate-limiting step in the enzyme-catalyzed conversion of 5-en-sterols to 4-en-3-one was the desorption of the sterol molecules from the monolayer into the active site of the enzyme at the interface. This appeared to be true both with pure sterol monolayers as well as with mixed monolayers containing phosphatidylcholine. PMID- 8431457 TI - Solubilization and functional reconstitution of the human placental taurine transporter. AB - The taurine transporter from purified human placental brush-border membranes was solubilized and reconstituted into proteoliposomes in a functional form. Solubilization was done with 2.5% cholate in the presence of 4 M urea. The proteins in the solubilizate were precipitated with 6% poly(ethylene glycol) and the precipitated proteins were reconstituted into proteoliposomes with an asolectin/protein ratio of 10:1. Under these experimental conditions, the taurine transport activity in the proteoliposomes was maximal. SDS-PAGE analysis of proteins, however, revealed that the proteoliposomes still contained a majority of the proteins originally present in the brush-border membranes. Uptake of taurine in the reconstituted proteoliposomes was obligatorily dependent on the presence of Na+ as well as Cl-. Substitution of Na+ with other monovalent cations such as K+ and Li+ reduced the taurine transport activity drastically. Similarly, substitution of Cl- with other monovalent anions such as SCN-, F-, I- and NO3- could support the transport activity only to a maximum of 30% of the control activity. In the presence of Cl-, the uptake rate was sigmoidally related to Na+ concentration, resulting in a Na+/taurine coupling ratio of 2:1. The apparent dissociation constant for Na+ was about 195 mM. In the presence of Na+, the uptake rate was hyperbolically related to Cl- concentration, indicating a Cl /taurine coupling ratio of 1:1. The apparent dissociation constant for Cl- was about 205 mM. The NaCl-dependent taurine uptake was stimulated by an inside negative membrane potential, showing that the uptake process was electrogenic. The uptake system was specific for beta-amino acids. The affinity of the system for taurine was high with an apparent dissociation constant of 2.7 +/- 0.1 microM. It is concluded that the taurine transporter can be dislodged from the placental brush-border membranes and reconstituted in a catalytically active form in proteoliposomes with no significant change in its characteristics. PMID- 8431458 TI - Expression of liver fatty acid binding protein alters plasma membrane lipid composition and structure in transfected L-cell fibroblasts. AB - Liver fatty acid binding protein, L-FABP, is an abundant protein that binds fatty acids in vitro. The effects of L-FABP on plasma membrane lipid composition, distribution, and physical structure were determined in intact L-cell fibroblasts transfected with cDNA encoding L-FABP. L-FABP expression altered plasma membrane phospholipids by decreasing both phosphatidylethanolamine and esterified oleic acid content, and increasing sphingomyelin. L-FABP also binds sterols and stimulates sterol uptake and esterification. The fluorescent sterol dehydroergosterol was used to examine sterol distribution in the transfected cell plasma membrane. Dehydroergosterol codistributed equally with the cholesterol in both the bulk membrane and the individual bilayer leaflets. The sterol/phospholipid ratio was decreased in the inner leaflet due to sterol depletion. Concomitantly, intermembrane sterol transfer from the rapidly exchangeable lateral sterol domains as measured by exchange of dehydroergosterol, was reduced. The fluidity of the plasma membrane was measured with the fluorescent molecule diphenylhexatriene by multifrequency (1-250 MHz) phase and modulation fluorometry. Both the bulk plasma membrane and the plasma membrane outer leaflet lipids were fluidized in transfected cells. These alterations of plasma membrane structure and composition are consistent with a role for L-FABP in regulating intracellular sterol and fatty acid distribution and thereby membrane lipid domain structure. PMID- 8431459 TI - Amiloride and 5-(N-ethyl-N-isopropyl) amiloride inhibit medium acidification and glucose metabolism by the fission yeast Schizosaccharomyces pombe. AB - We have investigated the mechanism by which amiloride and 5-(N-ethyl-N isopropyl)amiloride (EIPA) inhibit glucose-stimulated medium acidification in the fission yeast Schizosaccharomyces pombe. The addition of glucose to an unbuffered suspension of cells results in the extrusion of acid. This process was inhibited by diethylstilbestrol (DES), an inhibitor of the H(+)-ATPase (IC50 71 microM), and also by amiloride (IC50 824 microM) and EIPA (IC50 203 microM). The presence of 100 mM NaCl reduced the degree of inhibition observed for amiloride and EIPA, but had no effect on inhibition by DES. N-Methylglucosamine partially protected the cells against the effect of amiloride, but choline chloride did not, suggesting that sodium may be important in the action of amiloride. To establish the site of action of amiloride and EIPA, ATP hydrolysis assays were performed on isolated plasma membranes. H(+)-ATPase activity was inhibited by orthovanadate, but not by amiloride or EIPA. However, both amiloride and EIPA were found to inhibit the incorporation of radioactivity from labelled glucose in S. pombe, with IC50 values of 879 and 272 microM for amiloride and EIPA respectively. Again, 100 mM NaCl was found to reduce the effectiveness of inhibition. Amiloride had no effect on the uptake of 2-deoxyglucose under the same conditions, indicating that amiloride does not inhibit the glucose transporter. We propose that amiloride and EIPA disrupt glucose-induced acidification by inhibiting glucose metabolism. PMID- 8431460 TI - Effects of ultrasound on the steady-state transmembrane pH gradient and the permeability of acetic acid through bilayer lipid membranes. AB - The irradiation of bilayer lipid membranes with continuous ultrasound of a frequency of 8.2 MHz and a spacial peak time average (SPTA) intensity of 0.4 W/cm2 reduces the thickness of the unstirred layer up to 40% of its initial value under our conditions. This result was obtained from measurements of the transmembrane potential which appears after the addition of a protonophore in the presence of a gradient of acetic acid. Ultrasound exposure decreases this potential when the pH of the buffer solutions is much higher than the pK of CH3COOH and has no effect at low pH values. The latter can be explained by a simultaneous increase of the permeability of acetic acid and the buffer substances, respectively, due to ultrasound irradiation. PMID- 8431461 TI - Effects of platelet-activating factor and related lipids on dielaidoylphosphatidylethanolamine by DSC, FTIR and NMR. AB - The effect of platelet-activating factor (1-O-hexadecyl-2-acetyl-sn- glycero-3 phosphocholine, PAF) and two related molecules, 1-O-hexadecyl-sn-glycero-3 phosphocholine (LPAF) and 1-palmitoyl-sn-glycero-3- phosphocholine (LPC) on dielaidoylphosphatidylethanolamine (DEPE) lipid structure and polymorphism has been studied by differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) and 31P nuclear magnetic resonance (31P-NMR) spectroscopies. From the interaction of these molecules with DEPE it is concluded that all of them stabilize the lamellar phase with respect to the hexagonal HII phase and this effect is clear even at concentrations of these compounds as low as 1 mol%. It is also shown that, although they perturb the gel to liquid-crystalline phase transition of DEPE up to a similar extent, fluidizing the membrane, PAF but not LPAF or LPC, induces the presence of more than one peak in the calorimetric profile. Moreover, FTIR data indicate that lateral phase separations formed by PAF-rich phases are taking place. Remarkably, delta H of the main transition decreases at concentrations lower than 2 mol% but remains nearly constant up to 30 mol%. 31P-NMR measurements showed that all these molecules were capable of inducing isotropic signals in the spectra produced by molecules associated to membranes before micellization of the vesicles. PMID- 8431462 TI - Effects of 1,2-diacylglycerol and cholesterol on the hydrolysis activity of phospholipase D in egg-yolk phosphatidylcholine bilayers. AB - Effects of cholesterol (Chol) and 1,2-diacylglycerol (DAG) on the hydrolysis activity of phospholipase D (from Streptomyces chromofuscus) were studied in small unilamellar vesicles (SUV) of egg-yolk phosphatidylcholine (PC). 1,2 Diacylglycerol used here is derived from PC. Choline produced in the reaction was monitored by using a choline oxidase-oxygen electrode. Addition of 18.3 mol% Chol into SUV (2 mM PC) led to a small increase in the reaction rate. On the other hand, 18.3 mol% DAG in SUV brought about a 5-6-fold rate of choline production. The apparent maximum velocity, Vmax(app), increased by addition of DAG and Chol in SUV. In PC/Chol-SUV, the effect of increase in Vmax(app) was largely compensated by the increase in the apparent Michaelis constant, Km (app). The Chol and DAG molecules did not have significant effects on the kinetic parameters, when PC was solubilized in the micelles of heptaethylene glycol dodecyl ether. The effects of Chol and DAG are, therefore, not due to specific ones on the enzyme itself, but rather upon the bilayer-organization of the substrate. We discuss the activation of phospholipase D in terms of the influences of DAG and Chol on the structure of hydrophilic region and fluidity of the bilayers. PMID- 8431463 TI - Calorimetric studies of fully hydrated phosphatidylcholines with highly asymmetric acyl chains. AB - We have semi-synthesized 52 molecular species of saturated diacyl mixed-chain phosphatidylcholines. All 52 phosphatidylcholine molecules are highly asymmetrical with delta C/CL values in the range of 0.43-0.63. The aqueous dispersions of these phosphatidylcholines have been studied by the high resolution differential scanning calorimetric (DSC) technique. Upon heating, the lipid dispersions prepared individually from these 52 phosphatidylcholines all exhibit a sharp, single, endothermic peak at a characteristic temperature or Tm, implying that the self-assembled lipid molecules in excess water undergo the mixed interdigitated gel to the liquid-crystalline phase transition. The Tm values obtained from aqueous lipid dispersions prepared from these mixed-chain phospholipids have been analyzed based on the molecular packing model of the mixed interdigitated bilayer, and a linear relationship between the Tm and (delta C)-1 for various phospholipids at a constant value of delta is observed. Based on these linear relationships, empirical equations are derived to predict the Tm values for highly asymmetrical mixed-chain phosphatidylcholines with delta C/CL values in the range of 0.43-0.63. The predictive power of these empirical equations is shown to be very good, since a comparison between the predicted and the experimental data indicates that the largest relative error in Kelvin is only 0.4%. A table containing 81 predicted Tm values for highly asymmetrical mixed chain phosphatidylcholines is presented. The definitions of the various structural parameters such as delta C, CL, delta C/CL and delta are given in the text. PMID- 8431464 TI - Substrate-binding region of cytochrome P-450SCC (P-450 XIA1). Identification and primary structure of the cholesterol binding region in cytochrome P-450SCC. AB - Cytochrome P-450SCC (P-450 XIA1) from bovine adrenocortical mitochondria was investigated using a suicide substrate: [14C]methoxychlor. [14C]Methoxychlor irreversibly abolished the activity of the side-chain cleavage enzyme for cholesterol (P-450SCC) and the inactivation was prevented in the presence of cholesterol. The binding of [14C]methoxychlor and cytochrome P-450SCC occurred in a molar ratio of 1:1 and the cholesterol-induced difference spectrum of cytochrome P-450SCC was similar with the methoxychlor-induced difference spectrum. [14C]Methoxychlor-binding peptides were purified from tryptic-digested cytochrome P-450SCC modified with [14C]methoxychlor. Determination of the sequence of the amino-acid residues of a [14C]methoxychlor-binding peptide allowed identification of the peptide comprising the amino-terminal amino-acid residues 8 to 28. PMID- 8431465 TI - Catalytic properties of the CMP-N-acetylneuraminic acid hydroxylase from the starfish Asterias rubens: comparison with the mammalian enzyme. AB - The biosynthesis of N-glycolylneuraminic acid (Neu5Gc) was investigated in cell free extracts of the starfish Asterias rubens, which is one of the evolutionarily least-advanced species known to possess Neu5Gc-containing glycoconjugates. As in higher animals, Neu5Gc is synthesised in Asterias rubens by the action of a CMP Neu5Ac hydroxylase. Enzyme activity was detected in all starfish tissues tested, the turnover being the greatest in the gonads. The enzyme from this tissue has a temperature optimum between 25 and 33 degrees C and a pH optimum between pH 6.0 and 6.4. This hydroxylase exhibits many characteristics in common with the mammalian enzyme. For example, the enzyme is extracted in a predominantly soluble form. Oxygen and a reduced pyridine nucleotide are necessary for activity, with NADH being the most effective cofactor. Furthermore, the activation of the hydroxylase by exogenously added iron salts and the potent inhibitory effects of several iron ligands point to the involvement of a non-haem iron cofactor. The enzyme has a high affinity for the substrate CMP-Neu5Ac, the apparent Km being 18 microM. In contrast to the mammalian enzyme, the hydroxylase from Asterias rubens is not inhibited by increased ionic strength and cannot be activated by non-ionic detergents. Moreover, the CMP-Neu5Ac turnover increased linearily with increasing protein concentration. In accordance with other enzymes in starfish, seasonal changes in the CMP-Neu5Ac hydroxylase activity were also observed. PMID- 8431466 TI - Purification and properties of multiple molecular forms of yeast peptidyl prolyl cis-trans isomerase. AB - By hydrophobic chromatography on a butyl-Toyopearl 650 M column, yeast peptidyl prolyl cis-trans isomerase (PPIase) was separated into at least three molecular components (PPI-I, PPI-II and PPI-III) in their native forms. On the basis of the result of SDS-PAGE, PPI-II and PPI-III were highly purified and their molecular masses were estimated to be 16.5 and 17.2 kDa, respectively. However, PPI-I was still a mixture of two components with molecular masses of 23.3 and 24.1 kDa. The UV absorption spectrum of PPI-II was slightly different from that of PPI-III. In contrast, the CD spectra of the two proteins were essentially identical in the far-UV region. Upon addition of an immunosuppressant, cyclosporine A (CsA), the absorption spectra of the two highly purified proteins were subtly changed, which was indicative of some alterations in the microenvironments of the aromatic amino acid residues. The two proteins exhibited subtle but clear differences in the kinetic parameters (kc/Km) for the PPIase-catalyzed cis-trans isomerization and in the inhibition constants of CsA for the PPIase activity. These results lead to the conclusions that (1), a family of PPIases exists in one organism and that (2), one member of the family has multiple molecular forms with different substrate specificities and different affinities for the drugs (inhibitors). PMID- 8431467 TI - Isolation, partial characterisation, and amino acid sequence of alpha-lactalbumin from platypus (Ornithorhynchus anatinus) milk. AB - alpha-Lactalbumin was isolated from the whey fraction of platypus (Ornithorhynchus anatinus) milk by successive ion-exchange, hydrophobic interaction and gel-permeation chromatography. The purified protein modified the action of partially-purified galactosyltransferase from platypus milk to promote the synthesis of lactose, but had very little modifier effect on bovine galactosyltransferase. Platypus alpha-lactalbumin has 126 amino-acid residues (molecular mass about 14.3 kDa), including a three-residue insertion not found in other alpha-lactalbumins or c-type lysozymes. It appears to have two sites of post-translational modification, of which at least one is N-glycosylated, to give an apparent molecular mass of 23 kDa on SDS-PAGE. The platypus sequence shows a high degree of positional identity (41-48%) with the alpha-lactalbumins of other species. Although it has no lysozyme activity, platypus alpha-lactalbumin is more similar to mammalian lysozymes than is any eutherian or marsupial alpha lactalbumin, suggesting that this monotreme protein has evolved more slowly than other alpha-lactalbumins. PMID- 8431468 TI - Antibodies to recombinant fragment 212-276 of protein C specifically recognize the intact human molecule. AB - The peptide fragment Pro212-Ile276 of human protein C was produced as a part of a fusion protein in Escherichia coli. The identity of the peptide was confirmed by immunoblotting experiments using specific antibodies to intact protein C. The peptide Pro212-Ile276 was isolated from the fusion protein after mild hydrolysis with formic acid by gel filtration and reverse-phase HPLC. This peptide fragment was used to produce antibodies specific for the heavy chain of protein C which recognized native protein C present in blood plasma. Antibodies to intact protein C reacted also with the Pro212-Ile276 peptide fragment, indicating that this region is immunogenic in intact protein C and may represent a native epitope. PMID- 8431469 TI - Identification of a novel 4 kDa immunoglobulin-A-binding peptide obtained by the limited proteolysis of jacalin. AB - Jacalin, an IgA-binding lectin from jackfruit (Artocarpus heterophyllus) seeds, was isolated by the passage of PBS extracts of seeds over an affinity matrix containing IgA-Sepharose-4B. It was further purified by HPLC. When analyzed by SDS-PAGE under both reducing and nonreducing conditions, the native jacalin was dissociated into two subunits of 12 and 15.4 kDa. Both the subunits could bind IgA. Peptide mapping performed with radioiodinated jacalin indicated that both the subunits were susceptible to proteolysis by Staphylococcus aureus V8 proteinase. One degradation product was a small peptide of 4 kDa. This small proteolytic fragment also bound IgA. The amino-termini of the two major IgA binding subunits, 12 and 15.4 kDa, were identical. The 4 kDa IgA-binding proteolytic fragment of jacalin had a different amino-terminal sequence, suggesting that the region of jacalin which binds IgA does not remain close to the amino-terminus of the peptide. PMID- 8431470 TI - Selective oxidation of Met-192 in bovine alpha-chymotrypsin. Effect on catalytic and inhibitor binding properties. AB - Catalytic and inhibitor binding properties of bovine alpha-chymotrypsin, in which the Met-192 residue has been converted by treatment with chloramine T to the sulfoxide derivative (Met(O)192 alpha-chymotrypsin), have been examined relative to the native enzyme (alpha-chymotrypsin), between pH 4.5 and 8.0 (mu = 0.1), and/or 5.0 degrees C and 40.0 degrees C. Values of kcat, k+2 and/or k+3 for the hydrolysis of all the substrates examined (i.e., tMetAcONp, ZAlaONp, ZLeuONp, ZLysONp and ZTyrONp) catalyzed by native and Met(O)192 alpha-chymotrypsin are similar, as well as values of Km for the hydrolysis of ZLeuONp, ZLysONp and ZTyrONp. On the other hand, Ks and Km values for the hydrolysis of ZAlaONp and tMetAcONp are decreased by about 5-fold. Met-192 oxidation does not affect the kinetic and thermodynamic parameters for the (de)stabilization of the complex formed between the proteinase and the bovine basic pancreatic trypsin inhibitor. On the other hand, the recognition process between between alpha-chymotrypsin and the recombinant proteinase inhibitor eglin c from the leech Hirudo medicinalis is influenced by the oxidation event. Considering known molecular models, the observed catalytic and inhibitor binding properties of native and Met(O)192 alpha chymotrypsin were related to the inferred stereochemistry of the proteinase substrate and proteinase-inhibitor contact region(s). PMID- 8431471 TI - Studies on the subunit structure of textilotoxin, a potent presynaptic neurotoxin from the venom of the Australian common brown snake (Pseudonaja textilis). 3. The complete amino-acid sequences of all the subunits. AB - The complete amino-acid sequences of subunits A, B, C and D of textilotoxin, the presynaptic neurotoxin from the venom of the Australian common brown snake, Pseudonaja textilis, were determined. These confirmed that it is structurally the most complex of any of the known snake venom neurotoxins. Textilotoxin consists of 623 amino-acid residues in five subunits (subunit A, 118 residues; subunit B, 121 residues; subunit C, 118 residues; subunit D, two chains of 133 residues each). All subunits A, B, C and D contain the putative phospholipase A2 active site. Only subunit A showed any lethality on its own (4 mg/kg i.v. in mice). Subunit D contained two identical covalently-linked subunits and was weakly glycosylated. All subunits were necessary for maximum lethality at 1 micrograms/kg mice intraperitoneally. Details of the sequences of the subunits A, B and C are reported and interesting homology with other snake venom phospholipase A2 neurotoxins indicated. PMID- 8431472 TI - Thiamin-triphosphate-synthesizing activity of mutant cytosolic adenylate kinases: significance of Arg-128 for substrate specificity. AB - The thiamin triphosphate (TTP)-synthesizing activity and the ATP-synthesizing activity of two mutant enzymes of chicken cytosolic adenylate kinase whose Arg 128 was substituted by Trp (cAK1(Trp)) or Ala (cAK1(Ala)) were compared to those of the wild-type enzyme. The TTP-synthesizing activity of both the mutant enzymes was higher due to higher affinity to thiamin diphosphate (cAK1(Trp)) or a larger Vmax (cAK1(Ala)). The optimal pH shifted to pH 9.0 from pH 10.5. The ATP synthesizing activity of both the mutant enzymes was, on the other hand, markedly decreased with lower affinity for ADP and lower Vmax. These results suggest that Arg-128 plays an important role in the substrate specificity of the cytosolic adenylate kinase. PMID- 8431473 TI - Physical and conformational properties of staphylokinase in solution. AB - The structure of staphylokinase has been analyzed by solution X-ray scattering, dynamic light scattering, ultracentrifugation and ultraviolet circular dichroism spectroscopy. Staphylokinase has a radius of gyration of 2.3 nm, a Stokes radius of 2.12 nm and a maximum dimension of 10 nm. The sedimentation coefficient is 1.71 S. These physical parameters indicate that the shape of staphylokinase is very elongated. The protein molecule consists of two folded domains of similar size. The mean distance of the centres of gravity of the domains is 3.7 nm. The mutual positions of the two domains are variable in solution. Thus, the molecule is shaped like a flexible dumbbell. About 18% of the amino acids of staphylokinase are organized in helical structures, 30% are incorporated in beta sheets and 20% form turns. PMID- 8431474 TI - Photoaffinity labeling of cytochrome P-45011 beta with methyltrienolone as a probe for the substrate binding region. AB - Methyltrienolone, a synthetic steroid, was used as a photoaffinity ligand for steroid-binding proteins. The enzymatic activity of bovine adrenocortical cytochrome P-450(11) beta was inhibited by methyltrienolone in a competitive manner without exposure to light and cytochrome P-450(11) beta was photolabeled with methyltrienolone after irradiation with UV light. The addition of 11 deoxycorticosterone during photolabeling protected cytochrome P-450(11) beta from photolabeling. Photolabeled cytochrome P-450(11) beta was digested with TPCK treated trypsin and the peptide fragments were separated with a reverse-phase HPLC system. The labeled peptide was analyzed and its amino acid sequence was determined to be Trp428-Leu429-Asp430-Arg431. Alignment of the primary structure of cytochrome P-450(11) beta with that of cytochrome P-450cam revealed that the identified sequence corresponds to the region between the beta 3-sheet and L helix of cytochrome P-450cam. This region of mammalian cytochromes P-450 shows poor homology with that of cytochrome P-450cam, but is well-conserved, especially at Trp-428 and preceding amino acids, as the aromatic region. The present results demonstrate that the labeled sequence contributes in part to the formation of the substrate binding pocket of cytochrome P-450(11) beta which was not expected from the results of the primary sequence alignment with cytochrome P-450cam. PMID- 8431475 TI - Comparison of acceptor protein specificities on the formation of ADP ribose.acceptor adducts by arginine-specific ADP-ribosyltransferase from rabbit skeletal muscle sarcoplasmic reticulum with those of the enzyme from chicken peripheral polymorphonuclear cells. AB - We compared acceptor-protein specificities on the formation of ADP ribose.acceptor adducts by arginine-specific ADP-ribosyltransferase (EC 2.4.2.31) purified from rabbit skeletal muscle sarcoplasmic reticulum (SR) with those of the enzyme purified from chicken peripheral polymorphonuclear cells (heterophils). Major differences are as follows: (1), p33 and beta/gamma-actin, preferential endogenous acceptor proteins for the modification by the heterophil enzyme (Mishima, K., Terashima, M., Obara, S., Yamada, K., Imai, K and Shimoyama, M. (1991) J. Biochem. 110, 388-394 and Terashima, M., Mishima, K., Yamada, K., Tsuchiya, M., Wakutani, T. and Shimoyama, M. (1992) Eur. J. Biochem. 204, 305 311) were not modified by the SR enzyme. (2), The modification of p33 by the heterophil enzyme was enhanced by addition of polyanions such as DNA while the protein did not function as acceptor for modification by the SR enzyme even in the presence of DNA. (3), To ADP-ribosylate endogenous substrate Ca(2+) transporting ATPase (EC 3.6.1.38) of rabbit skeletal muscle SR, the SR ADP ribosyltransferase required polycations such as poly(L-lysine), whereas the heterophil enzyme modified the ATPase in the absence of poly(L-lysine). These results suggest that vertebrate arginine-specific ADP-ribosyltransferase prefers its own acceptor protein for the modification. Some other properties of the SR and the heterophil ADP-ribosyltransferases were also compared. PMID- 8431476 TI - Differential scanning calorimetric study of 5-enolpyruvoyl shikimate-3-phosphate synthase and its complexes with shikimate-3-phosphate and glyphosate: irreversible thermal transitions. AB - The thermal denaturation of native Escherichia coli 5-enolpyruvoyl shikimate-3 phosphate (EPSP) synthase, its binary complex with shikimate-3-phosphate (S3P) and its ternary complex with S3P and glyphosate have been studied using highly sensitive differential scanning calorimetry (DSC). All observed transitions are strongly scanning-rate-dependent and irreversible. Consistent with these observations, the data were better fit by a simple irreversible model than by the controversial reversible model more commonly employed. The results obtained provide additional support for the application of irreversible models to the thermal denaturation of proteins. The calculated parameters, activation energy (Ea), enthalpy of denaturation (delta H) and transition temperature (Tm), obtained from fitting to an irreversible model agree well with values obtained from approximation techniques. Further, the results show that the formation of the ternary complex greatly enhances the thermal stability of the enzyme (delta Tm = 10.6 degrees C), while the binding of S3P alone increases the transition temperature only slightly (delta Tm = 3 degrees C). The heat of binding calculated at the transition temperature also demonstrates the greater stability of the ternary complex (delta H = -70 kcal/mol) versus the binary complex (delta H = -10 kcal/mol). PMID- 8431477 TI - Chemical modification studies of the active site of glucosamine-6-phosphate synthase from baker's yeast. AB - Glucosamine-6-phosphate synthase from baker's yeast has been purified 100-fold with a final recovery of 70%. The purification procedure involved thiol-affinity chromatography. Chemical modification studies of the enzyme revealed the presence of cysteine, Glu/Asp-carboxyl and probably histidine at the glutamine binding site and, on the other hand, arginine and probably another histidine at the D fructose 6-phosphate binding site. A few glutamine analogs, including 6-diazo-5 oxo-L-norleucine (DON), anticapsin and N3-(4-methoxyfumaroyl)-L-2,3 diaminopropanoic acid (FMDP), were shown to inactivate the enzyme in a time- and concentration-dependent manner. Anticapsin, the most active in the series, exhibited an inactivation constant, Kinact, of 9.5.10(-6) M. PMID- 8431478 TI - The differential effects of carbon monoxide and oxygen on the pressure dissociation of Lumbricus terrestris hemoglobin. AB - We have explored the subunit affinities of Lumbricus terrestris hemoglobin (LtHb) under a variety of conditions using high-pressure spectroscopy. While only small changes were observed for LtHb-oxy below 1.0 kbar, higher pressures resulted in a 1000 cm-1 red shift and 2-fold increase in fluorescence intensity with a concomitant 12-fold decrease in scattering intensity, all of which reached completion by approx. 2.2 kbar. In the presence of 1 M MgCl2 or at acidic pH (4.2), the curves shifted by 400 and 1000 bar corresponding to significant destabilization. At pH 9.1, the initial spectral parameters were almost equal to the final endpoints and were unaffected by pressure. While the pressure curve of the CO form was similar to the oxy form at pH 7.2, the midpoints of the other samples were shifted to higher pressures relative to their oxy counterpart, indicating tighter subunit contacts. This stabilization was unexpected based upon the sequence homology to vertebrate hemoglobins, and the minimal structural differences between these two liganded forms of human hemoglobin. These data indicate that the differences are the result of the additive nature of the interactions involved in subunit packing whose effects become significant in larger aggregates. PMID- 8431479 TI - The differential lysis of phosphoester bonds by nuclease P1. AB - The hydrolysis by nuclease P1 of the 16 common deoxydinucleoside monophosphates was examined. The rates of hydrolysis of phosphodiester bond differ by more than two orders of magnitude; dinucleotide monophosphates of the type d(TpN) being most resistant and d(GpN) being next most resistant. The profiles of a mixture of the 16 common dinucleoside monophosphates and of DNA after partial hydrolysis by nuclease P1 and simultaneous treatment with acid phosphatase were compared. The resultant profiles are very similar, except for the appearance of 5 methyldeoxycytidine in the latter. Similar profiles are also obtained from a mixture of dinucleoside monophosphates and from DNA exposed to ionizing radiation beforehand. The 8-hydroxyguanine lesion and a formamido remnant of thymine appear in both profiles as a modified nucleoside and as modified dinucleoside monophosphate respectively. These results suggest that certain radiation induced DNA lesions can be selectively postlabelled based on their resistance to hydrolysis by nuclease P1. The nature of the nuclease P1-substrate interaction is discussed. PMID- 8431480 TI - Characterization of phosphoramidon-sensitive metalloproteinases with endothelin converting enzyme activity in porcine lung membrane. AB - Endothelin-1 (ET-1), a 21 amino-acid potent vasoconstrictor peptide, is produced from the biologically inactive intermediate big ET-1 via an endoproteolytic cleavage between Trp-21 and Val-22 by endothelin converting enzyme (ECE). cDNA sequence analysis predicts that the two other members of the endothelin family, ET-2 and ET-3, are also generated from the corresponding intermediates called big ET-2 and big ET-3, respectively. The metalloproteinase inhibitor phosphoramidon inhibited the conversion of big ET-1 into mature ET-1 both in vivo and in cultured endothelial cells, suggesting that ECE may be a neutral metalloproteinase. In this study, we solubilized and partially purified ECE from the membrane fraction of porcine lung. Using gel filtration chromatography, we separated two distinct ECE activities, designated M1 (apparent molecular mass approx. 300 kDa) and M2 (approx. 65 kDa). Optimum pH for the cleavage of big ET-1 by M1 and M2 was 7.0 and 7.5, respectively. M1 efficiently converted human big ET 1(1-38) to ET-1, but not human big ET-2(1-37) or human big ET-3(1-41)-amide. In contrast, M2 converted both big ET-1 and big ET-2, but not big ET-3. M1 was inhibited by phosphoramidon (IC50 approx. 1 microM) but not by thiorphan or bacitracin. In contrast, M2 was inhibited by much lower concentrations of phosphoramidon (IC50 approx. 0.3 nM), as well as by thiorphan and bacitracin. ECE activity in M1 was able to bind to a concanavalin A-agarose column and was eluted by alpha-methyl-D-glucoside, indicating that the ECE is glycosylated. From these results, M1 and M2 from the porcine lung membrane are similar to the candidate of ECE in endothelial cells and neutral endopeptidase in kidney (EC 3.4.24.11), respectively. Taken in conjunction with the previous finding that neither thiorphan nor bacitracin affected the conversion of endogenously synthesized big ET-1 in cultured endothelial cells, we conclude that physiologically relevant ECE found in the endothelial cells is more similar to M1 than to M2. PMID- 8431481 TI - A model for prosthetogenic enzyme amplification assays. AB - A mathematical model describing the behaviour of a new class of prosthetogenic enzyme amplification assays is described. The predictions of the model are favourably compared with an enzyme amplification assay for alkaline phosphatase. The model is used to kinetically characterise and optimise the enzyme amplification assay. PMID- 8431482 TI - Characterization of two novel subunits of the alpha-class glutathione S transferases of human liver. AB - More than 85% of the complete amino-acid sequence of the alpha-class glutathione S-transferase omega (GST omega) of human liver, described for the first time in this communication, show that GST omega is a heterodimer of two closely related novel alpha-class GST subunits. The sequences of these subunits, omega 1 and omega 2, have over 97% homology between them and are also highly homologous to the two alpha-class subunits characterized previously. Characterization of these two novel alpha-class subunits described in this report would explain the molecular basis for high degree of heterogeneity observed among the alpha-class human GSTs. PMID- 8431483 TI - Bile salt-activated lipase. A multiple function lipolytic enzyme. PMID- 8431484 TI - Effect of chemically modified GM1 and neoglycolipid analogs of GM1 on liposome circulation time: evidence supporting the dysopsonin hypothesis. AB - The sugar group of the ganglioside GM1 has been modified by periodate oxidation, reduction or reductive amination. The negative charge of sialic acid of GM1 has also been removed by methylation or reductive hydrolysis. A series of neoglycolipid analogs of GM1 were synthesized by coupling the GM1 oligosaccharide (GM1OS) to dioleoylphosphatidylethanolamine (DOPE) via different spacer arms. The individual GM1 derivatives were incorporated into egg phosphatidylcholine/cholesterol liposomes and tested in mice in order to see whether they were effective in prolonging liposome circulation. The oxidized GM1 did not show any ability to prolong circulation. However, the lost activity after oxidation was completely recovered by the subsequent reduction step. A series of aminated GM1 derivatives were prepared via oxidation followed by reductive amination with various substituted amines. beta-Alanyl GM1 showed a comparable activity to the native GM1, while other aminated GM1S showed reduced activity in terms of prolonging circulation of liposomes. Blocking the negative charge of sialic acid by methylation did not greatly lessen the activity, and removing the carboxyl group of sialic acid by reductive hydrolysis reduced the activity by only approx. 20%. Among the neoglycolipid analogs of GM1 only GM1OS directly conjugated to DOPE was effective in prolonging the circulation, whereas conjugates with a spacer of various length were not effective. These results emphasize the importance of the molecular structure of GM1 for its functional ability to prolong the liposome circulation. Furthermore, modifications which abolish the cholera toxin-binding activity of GM1 also decrease the ability to prolong the circulation time of the liposomes, and vice versa. Such strong correlation further supports the idea that the specific recognition of GM1 oligosaccharide by putative dysopsonin(s) is responsible for the ability to prolong the liposomes circulation time. PMID- 8431485 TI - Hepatic uptake and metabolism of ingested 24-hydroxycholesterol and 24(S),25 epoxycholesterol. AB - Although two hepatic sterol metabolites, 24(S)-hydroxycholesterol and 24(S),25 epoxycholesterol, are thought to be important regulators of cholesterol biosynthesis, nothing is known of their degradation and disposal in liver, nor of the mechanisms that regulate their levels. As an initial approach to these questions the two sterols were administered intragastrically, as a bolus, to mice and their hepatic accumulation and conversion to more polar compounds were examined as a function of time. These results were compared to those obtained for cholesterol and for the unnatural epimer of one of the oxysterols, 24(R) hydroxycholesterol. Maximum concentrations of the three oxysterols in liver were reached by approx. 4 h and then declined to control levels by 8 h. More polar neutral and acidic metabolites were found in the liver extracts. Radiolabeled oxysterols and their metabolites were found in bile glands. In comparison, the amounts of hepatic free and esterified cholesterol and of acidic products formed from it increased gradually over the measured period of time. Rates of conversion of the two 24-hydroxycholesterol epimers into acidic compounds by a liver mitochondrial fraction in vitro exceeded those of 24(S),25-epoxycholesterol and cholesterol. 24(S)-Hydroxycholesterol did not lower the level of hepatic HMG-CoA reductase activity, consistent with the absence of any significant accumulation of the free sterol. Accumulation of appreciable amounts of free 24(S),25 epoxycholesterol was associated with lowered levels of reductase. The existence of hepatic systems for the rapid inactivation and degradation of the oxysterols is consistent with their postulated role in the regulation of cholesterol synthesis. PMID- 8431486 TI - Responses of purified phospholipases A2 to phospholipase A2 activating protein (PLAP) and melittin. AB - The role of the phospholipase A2 (PLA2) stimulating protein PLAP in the regulation of PLA2 activity was assessed by determination of the effects of PLAP on two purified PLA2s. An approx. 14 kDa enzyme was purified from mouse thymoma cells, EL-4 cells, by cation ion exchange HPLC and immunoaffinity HPLC (with antiserum to the N-terminal sequence of an inflammatory exudate PLA2). An approx. 110 kDa enzyme was purified from mouse mammary carcinoma derived cells by sequential hydrophobic, anion exchange, hydroxyapatite and gel filtration HPLC. Neither PLAP nor melittin, an immunologically related PLA2 stimulating peptide from bee venom, increased the activity of the high molecular weight enzyme. In contrast, there was more than a 20-fold stimulation of the low molecular weight PLA2 by PLAP and an approx. 5-fold stimulation by melittin. The stimulation of enzyme activity by PLAP was observed at a protein to phospholipid ratio of 1:10(6) while the ratio of melittin to phospholipid was 1:3. Thus, PLAP mediated stimulation of PLA2 activity may include an interaction between PLAP and the enzyme, in contrast to melittin stimulation, which involves interactions between melittin and phospholipid. PMID- 8431487 TI - Detection of a point mutation in cholesteryl ester transfer protein gene by polymerase chain reaction-mediated site-directed mutagenesis. AB - We describe a method for the rapid and non-radioactive examination of DNA samples for a mutation of cholesteryl ester transfer protein using a polymerase chain reaction-mediated site-directed mutagenesis. CETP deficiencies were studied in 554 Japanese subjects (370 men, 184 women) aged between 18 and 91 (mean 48.3 years). By this method, we detected one homozygote and 3 heterozygotes of the CETP deficiency. PMID- 8431488 TI - Relationship between the size and phospholipid content of low-density lipoproteins. AB - In studies performed in vivo and in vitro, it has been found that the Stokes' diameter of human low-density lipoproteins (LDL) correlates positively and significantly with the molar ratio of phospholipid/apo B in LDL but not with the LDL molar ratios of either cholesterol/apo B or triacylglycerol/apo B. It has been concluded that the phospholipid content of LDL is an important determinant of LDL size. PMID- 8431489 TI - Apolipoprotein A-I stabilizes phospholipid lamellae and thus prolongs nucleation time in model bile systems: an ultrastructural study. AB - To explore the mechanisms whereby apolipoprotein A-I inhibits the nucleation of cholesterol crystals, we performed an ultrastructural study using supersaturated model bile systems. Vesicles, micelles and phospholipid lamellae were consistently separated by gel permeation chromatography either in the absence or presence of apolipoprotein A-I. Furthermore, apolipoprotein A-I coeluted with phospholipid lamellae. A sequential study using transmission electron microscopy revealed that phospholipid lamellae without apolipoprotein A-I showed a rapid transformation, with formation of multilamellae and fusion followed by microcrystal nucleation. In contrast, lamellae with apolipoprotein A-I showed little transformation. In conclusion, apolipoprotein A-I stabilizes the phospholipid lamellae, thereby inhibiting the nucleation of cholesterol crystals in supersaturated model bile systems. PMID- 8431490 TI - Amphipathic alpha-helical peptides based on surfactant apoprotein SP-A. AB - Three peptides based on the putative amphipathic helical region of the major pulmonary surfactant apoprotein (SP-A) were synthesized by solid-phase techniques, mixed with DPPC and tested for efficacy as lung surfactants in an in vitro adult rat lavaged lung model. The peptides correspond to residues 81-102 (SP-A81-102) and 78-101 (SP-A78-101) of the native human sequence and an analog with increased hydrophobicity, Leu84,90SP-A78-101. Neither native sequence was effective in simple mixtures with DPPC. However, substitution of leucine residues for Asp84 and Thr90 of SP-A81-102 yielded a peptide which was active in mixtures with DPPC, restoring quasi-static lung compliance to 90% of the unlavaged value. In the absence of peptide, DPPC had no effect on the P-V curve of the lavaged lung. The activity of the Leu84,90 analog correlated with an increased amphipathic alpha-helical potential and an improvement in several predictive parameters for lipid-binding. The similarities between this active peptide and other active amphipathic alpha-helical peptides lend support to the hypothesis that amphipathic alpha-helical potential and the size of the hydrophobic face are critical for functional synthetic surfactant peptides in simple mixtures with dipalmitoylphosphatidylcholine. PMID- 8431491 TI - The surface properties of lung 36 kDa Ca(2+)-dependent phospholipid-binding protein. AB - The intrinsic surface activity of a 36 kDa rabbit lung calcium-dependent phospholipid-binding protein (PLBP), a member of the annexin family of such proteins, at the air/water interface has been determined from measurements of surface tension of aqueous solutions, and surface concentration of 14C-labeled PLBP adsorbed from aqueous solution in the absence and presence of Ca2+. It was also possible to spread insoluble monolayers of PLBP to determine surface pressure vs. surface concentration isotherms, as well as surface elasticity and surface viscosity as a function of frequency from electrocapillary wave diffraction measurements. PLBP has been shown to exhibit significant intrinsic surface activity at the air/water interface, comparable to a variety of other hydrophobic proteins known to be quite surface active. In all cases, surface properties were enhanced by the presence of Ca2+, particularly the degree of surface viscoelasticity at close-packing in the monolayer. This is believed to reflect changes in protein conformation at the surface. PMID- 8431492 TI - Occurrence of phosphonotetraglycosyl ceramide in the sea hare Dolabella auricularia. AB - Two kinds of phosphonoglycolipids were isolated from the sea hare Dolabella auricularia. One was phosphonopentaglycosyl ceramide with the same structure as that of the phosphonoglycolipid obtained from the sea hare Aplysia kurodai. The other, phosphonotetraglycosyl ceramide, was discovered in this study. Its structure was determined to be 3-O-Me-Gal alpha 1-3(AEP-6Gal alpha 1-2)Gal beta 1 4Glc beta 1-1-ceramide. The presence of tetraglycosyl and pentaglycosyl ceramides, the backbone structures of phosphonoglycolipids in the neutral glycolipid fraction, indicate that these neutral glycolipids are precursors of the phosphonoglycolipids. PMID- 8431493 TI - The shuttling of dolichol between VLDL and HDL: involvement of a protein factor from lipoprotein-deficient human serum. AB - The occurrence of a dolichol transfer factor in LPDS has been demonstrated using three different transfer assays. Applying a three step purification procedure, the transfer factor could be enriched 4000-5000-fold with a recovery of 1-2%. SDS gel electrophoresis revealed a molecular weight of 64 kDa. Kinetics as well as the influence of a series of effectors were studied. Transfer was not accompanied by a concurrent esterification and the HDL3 subpopulation showed the highest acceptor capacity. The transfer factor also affected liposomal stability based on calcein fluorescence dequenching upon release. The characteristics of this dol-TP are discussed in view of these other plasma LTPs. Dol-TP might play a role in dolichol transfer from VLDL to HDL, observed in vivo. PMID- 8431494 TI - Early effects on mitochondrial and peroxisomal beta-oxidation by the hypolipidemic 3-thia-fatty acids in rat livers. AB - A single administration of 3-thiadicarboxylic and tetradecylthioacetic acids stimulates both mitochondrial and peroxisomal beta-oxidation and lowers plasma triacylglycerol levels. An increased rate of mitochondrial beta-oxidation and carnitine palmitoyl-transferase activity was established after 3 h and this was accompanied by a lowering of plasma triacylglycerol. Peroxisomal beta-oxidation, however, remained unchanged up to 8 h and was significantly increased after 12 h. These results suggest that after a single administration of 3-thia fatty acids mitochondrial beta-oxidation precedes peroxisomal beta-oxidation. Furthermore, they show that the observed tricylglycerol-lowering effect, which is established early (3-4 h) after the administration of 3-thia fatty acids, is initially due to an increased mitochondrial beta-oxidation. PMID- 8431495 TI - Type II phospholipase A2 in human gestational tissues: subcellular distribution of placental immuno- and catalytic activity. AB - The aims of this study were to determine the subcellular distribution of Type II phospholipase A2 immunoactivity (irPLA2) and in vitro net PLA2 catalytic activity in human term placenta and to establish the efficacy of previously utilised homogenisation procedures with respect to the quantitative recovery of Type II PLA2 immunoreactive and in vitro net PLA2 catalytic activity. Type II PLA2 immunoactivity and PLA2 catalytic activity recovered in 900 x g supernates prepared from placental tissue (n = 3) homogenised in low ionic strength media (sucrose 0.32 M Hepes 20 mM; phosphate-buffered saline or phosphate-buffered saline containing 3 mM EGTA) was less than 10% of that recovered following homogenisation in high ionic strength medium (ammonium sulphate 10%, w/v). The subcellular distribution of Type II PLA2 immunoactivity and PLA2 catalytic activity was established by the differential centrifugation (10,000, 20,000 and 100,000 x g) of placental homogenates (n = 3). Although Type II PLA2 immunoactivity was equally distributed throughout the particulate subcellular fractions examined, PLA2 catalytic activity increased by comparison in 100,000 x g particulate material. This apparent dissociation between irType II PLA2 and catalytic activity may indicate the presence of other types of PLA2 in this fraction. The data obtained in this study indicate that previous studies which have utilised low ionic strength extractions of human gestational tissue to characterise PLA2 catalytic activity and subcellular distribution have largely excluded the contribution made by Type II PLA2. Consequently, much of the available published data on the role of PLA2 in human parturition is inadequate. A reappraisal of this enzyme's contribution to the biochemical events associated with human pregnancy and labour is required. PMID- 8431496 TI - Total parenteral nutrition and plasma lipoproteins in the rat: evidence for accelerated clearance of apo-A-I-rich HDL. AB - The effect of total parenteral nutrition (TPN) containing fat on plasma lipoproteins and apo-A-I-rich HDL catabolism was studied in the rat. TPN rats were intravenously infused for 5 days with a nutritive mixture containing amino acids, lipids (Intralipid 20%) and glucose. In spite of similar plasma levels of total cholesterol in TPN and control orally fed rats, density gradient ultracentrifugation of plasma samples gave evidence of marked differences in the lipoprotein profiles. In the density range 1.010-1.040, were found elevated amounts of apo-B-100 and apo-B-48 containing lipoproteins, as well as an increase in free cholesterol and phospholipids, the latter indicating that the plasma of TPN rats contained abnormal lipoprotein-X-like particles. The level of apo-E-rich HDL (density: 1.040-1.063) was not markedly changed, whereas that of typical HDL (d > 1.063) was lowered, with less apo-A-I and apo-A-IV, and low amounts of cholesterol and phospholipids were found in the most dense HDL3 fractions (d > 1.090) containing the bulk of apo-A-I-rich particles. After intravenous infusion of homologous [14C]sucrose-labelled HDL3, the clearance of these particles was 2 fold faster in TPN than in control rats, with a tissue uptake increased in the liver (+40%) and decreased in the small and large intestines (-60%). Because the pool of apo-A-I-rich HDL was dramatically reduced after 5 days of artificial feeding, the absolute catabolic rate of these lipoproteins was similar in the two groups. These data suggest that, in TPN rats lacking of chylomicron coat components as a source for HDL material, the fall in plasma levels of apo-A-I rich HDL resulted mainly from accelerated turnover of these particles, mediated by increased uptake by the liver. Conversely, mucosa atrophy was probably involved in the reduced uptake of apo-A-I-rich HDL by the gastrointestinal tract. PMID- 8431497 TI - Reaction of lecithin: cholesterol acyltransferase with a water soluble substrate: effects of surfactants. AB - The reaction of fatty acid esters of p-nitrophenol, including the butyrate ester (PNPB) with lecithin: cholesterol acyltransferase (LCAT) has already been described (Bonelli, F.S. and Jonas, A. (1989) J. Biol. Chem. 264, 14723-14728) as a means to investigate the events at the active site of LCAT in the absence of interfacial interactions. Since various surfactants at low concentrations are known to affect the reaction of LCAT with particulate substrates, we set out to analyze their effects on the enzyme in solution using the PNPB substrate to monitor enzyme activity. All the surfactants studied by us (sodium dodecyl sulfate (SDS), dodecyltrimethyl ammonium bromide (DTAB), sodium laurate, sodium cholate, Triton X-100, and BIGCHAP) were able to interact with LCAT below their critical micellar concentrations. The ionic detergents caused inhibition of LCAT at concentrations ranging from 10(-4) to 10(-3) M, whereas the two nonionic detergents actually activated the enzyme in a similar concentration range. From the kinetic constants, the patterns of inhibition, and the well documented effects of the detergents on other proteins, we propose that SDS binds cooperatively to LCAT and elicits inhibitory structural changes; laurate and cholate bind to specific sites either in the active site cavity or in negative effector sites elsewhere; and the nonionic detergents may produce a slight interfacial activation of the phospholipase reaction near their critical micellar concentrations. PMID- 8431498 TI - Inhibition of fatty acid synthesis in rat hepatocytes by exogenous polyunsaturated fatty acids is caused by lipid peroxidation. AB - Rat hepatocyte long-term cultures were utilized to investigate the impact of different polyunsaturated fatty acids (PUFA) on the insulin-induced de novo fatty acid synthesis in vitro. The addition of 0.5 mM albumin-complexed oleic, linoleic, columbinic, arachidonic, eicosapentaenoic or docosahexaenoic acid resulted in a marked suppression of fatty acid synthesis. By evaluation of cell viability (determined as the leakage of lactate dehydrogenase (LDH) it turned out, that the antioxidant used (50 microM alpha-tocopherol phosphate) had a low antioxidant activity, resulting in cytotoxic effects by the peroxidized PUFA. Arachidonic acid and eicosapentaenoic acid showed a dose- and time-dependent cytotoxicity. Two other antioxidants: 50 microM alpha-tocopherol acid succinate and 1 microM N,N'-diphenyl-1,4-phenylenediamine, both proved more efficient than alpha-tocopherol phosphate. There was a significant correlation between LDH leakage and inhibition of fatty acid synthesis. Lipid peroxidation, measured as thiobarbituric acid-reactive substances, also showed a significant correlation with the degree of inhibition of fatty acid synthesis. Furthermore, PUFA had no inhibitory effect on fatty acid synthesis when peroxidation was minimized by the use of proper antioxidants. These data indicate that PUFA in vitro inhibit the insulin-induced de novo fatty acid synthesis in hepatocytes from starved rats, due to cytotoxic effects caused by lipid peroxidation. PMID- 8431499 TI - Determination of the HMG-CoA reductase inhibitors simvastatin, lovastatin, and pravastatin in plasma by gas chromatography/chemical ionization mass spectrometry. AB - A general method for the assay of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase inhibitors lovastatin, pravastatin, and simvastatin in plasma has been developed and validated. The analytes are isolated from plasma by a solid phase extraction procedure which separates the lactone and acid forms of the drugs. The lactone is converted to the acid form, which is subsequently derivatized by pentafluorobenzylation of the carboxyl group, and trimethylsilylation of the hydroxyl functions. Derivatized samples of intrinsic and converted acid are assayed by gas chromatography/mass spectrometry using negative chemical ionization mass spectrometry. The method has sufficient sensitivity, precision, accuracy, and selectivity for the analysis of clinical samples containing the drugs administered at therapeutic doses. The method thus permits determination of both the lactone and hydroxy acid forms of lovastatin and simvastatin, and is also applicable to the assay of pravastatin. PMID- 8431500 TI - Mass spectrometric studies of the toxaphene components 2-exo,3-endo,5-exo,6 endo,8,8,10,10-octachlorobornane (T2) and 2-exo,3-endo,5-exo,6-endo,8,8,9,10,10 nonachlorobornane (T12). AB - The electron capture negative ion mass spectra of the title compounds show prominent [M-Cl]- ions, and low-abundance ions formed by further elimination of HCl or Cl2. The electron ionization positive ion mass spectra are complex, but structurally informative fragmentations are observed. In particular, fragmentations involving elimination of C2H2Cl2, and not of C2H4, C2H3Cl, C2HCl3 or C2Cl4, indicate that two chlorines are bound to the C2-C3 and C5-C6 units of a norbornane skeleton. Furthermore, from M+., elimination of HCl is enhanced with respect to Cl., relative to toxicants A and B, which are major components of commercial toxaphene; this result suggests that one chlorine atom is bound to each of carbons 2, 3, 5 and 6. Both compounds have CHCl2 substituents. Several of the fragmentation pathways appear to terminate at ions that may be tropylium analogues. PMID- 8431501 TI - Membrane mass spectrometer inlet for quantitation of nitric oxide. AB - Nitric oxide (NO) is an important physiological and biochemical messenger that may be involved in endogenous carcinogenesis and cell toxicity via formation of N nitroso compounds or direct DNA damage by nitrosating agents arising from the reaction of NO with O2. To study the reaction of NO with O2 in model systems and the formation and disappearance of NO in more physiological systems such as cell cultures, we adapted and optimized a membrane mass spectrometer inlet specifically for such analyses. The inlet consisted of Silastic tubing inserted into a Swagelok 'tee', which was attached to the mass spectrometer via the tuning probe. Kinetics of NO disappearance can be followed under electron impact conditions until NO2 interferes via the formation of NO+ during fragmentation of NO2+. The aqueous NO concentration for minimum detection was determined to be 1.4 microM. The inlet response time to step changes in aqueous NO concentrations was 7.0 s, fast enough to permit real-time measurements of aqueous NO changes upon addition of O2. Finally, the depletion of aqueous NO was observed in the presence of O2. The relative steady state responses of inlets designed for gas or aqueous samples, and their relative response times, are explained by an analysis based on mass transfer theory. PMID- 8431502 TI - Quantification and kinetics of 25-hydroxyvitamin D3 by isotope dilution liquid chromatography/thermospray mass spectrometry. AB - A liquid chromatography/thermospray mass spectrometry method has been developed and used to measure the plasma levels and half-life of 25-hydroxyvitamin D3 in adults. The mean plasma levels of 25-hydroxyvitamin D3 averaged 40 ng ml-1 (n = 4) in summer and 30 ng ml-1 (n = 6) in winter. The method was also used to determine the half-life of serum 25-hydroxyvitamin D3 in subjects maintained on either high or low-fiber diets who had been given an intravenous infusion of (6,19,19-2H3)25-hydroxyvitamin D3 sufficient to label 5% of their estimated body pools. The half-life was determined to be 10.4 days (n = 4), which is approximately 50% of the currently accepted value of 19 days, determined using radiolabeled methods. This difference may be due to kinetic isotope effects arising as a result of the tritiated compounds being labeled at sites that undergo Cyt-P450-catalyzed oxidations. PMID- 8431503 TI - Electrospray mass spectrometry for characterization of lipid A from Enterobacter agglomerans. AB - Negative ion and positive ion electrospray mass spectrometry have been employed to characterize the lipid A mixture produced by hydrolysis of lipopolysaccharides from Enterobacter agglomerans, a Gram-negative bacterium commonly found in field cotton. Neutral monophosphoryl lipid A molecules form stable anions via deprotonation, but adduct formation via cation attachment occurs in low yield. Dephosphorylated lipid A molecules, on the other hand, readily form adducts with Na+, whereas deprotonation occurs in low yield. The mass spectra of lipid A produced by E. agglomerans reveal the presence of lipid A ions which differ in the nature of attached fatty acid side chains. At least two heptaacyl forms of lipid A are present, one of which has a structure which appears to be the same as the structure of heptaacyl lipid A produced by Salmonella minnesota. The second structure differs only by the nature of the side chain at position 3' of the disaccharide backbone where a hydroxymyristoyloxymyristoyl group replaces the myristoyloxymyristoyl substituent. Collisionally activated dissociations prior to mass analysis enable the identification of fragment ions which can be distinguished from at least eight intact deprotonated molecules present in crude lipid A. PMID- 8431504 TI - Analysis of mercapturic acid conjugates of xenobiotic compounds using negative ionization and tandem mass spectrometry. AB - Mass spectra of mercapturic acid conjugates of two xenobiotic products of lipid peroxidation (trans-4-hydroxy-2-hexenal and trans-4-hydroxy-2-nonenal) as well as conjugates of 1,3-dichloropropene, styrene oxide, 1,2-naphthalene oxide and alpha chlorotoluene were obtained using fast atom bombardment or negative chemical ionization. Fragmentation pathways were investigated using linked scan and mass analyzed ion kinetic energy spectrometric techniques. Characteristics of the spectra obtained using different ionization and sample introduction techniques are compared. Deprotonated molecular ions of mercapturic acids gave simple daughter ion spectra, with the dominant mode of decomposition involving cleavage of C-S bonds giving a characteristic neutral loss of 129 Da. Screening for mercapturates in urine samples was performed using neutral loss scanning and yielded limits of detection in the low nanogram per milliliter range. Quantitative analysis of the S-benzyl mercapturic acid at 1 p.p.b. in urine has been demonstrated using combined gas chromatography/electron capture mass spectrometry with d3-S-benzyl mercapturic acid as internal standard. PMID- 8431505 TI - Optimization of sample recovery from the nitrocellulose support used in plasma desorption mass spectrometry and its use for multiple analyses of insulin. AB - The parameters for recovery of sample from the nitrocellulose support used in plasma desorption are optimized. The losses in washing, in situ reactions, and extraction procedures are quantitatively evaluated. At least 80% of the sample can be effectively extracted or transferred to a polyvinyl difluoride membrane with 2-propanol-water mixture in the range 1:1-2:3 v/v. Quantitative losses of insulin during washing procedures vary from 0 to 50% depending on the washing procedure used. The losses in in situ reactions are negligible. Optimization of the procedures allows several successive procedures to be carried out after adsorption of 1 nmol of insulin on the nitrocellulose support. These include in situ reaction, extraction of A and B chains followed by S-alkylation, chain separation by high-performance liquid chromatography, mass spectrometric analysis of the separated chains, and finally automatic sequence after transfer to the sequenator. PMID- 8431506 TI - Fragmentation of parathyroid hormone, a 9.4 kDa polypeptide, in liquid secondary ion mass spectrometry. PMID- 8431507 TI - Enhanced in vitro tumor cell retention and internalization of antibody derivatized with synthetic peptides. AB - The Fab fragments of two antitumor monoclonal antibodies, NR-ML-05 and NR-LU-10, have been covalently derivatized with synthetic peptides designed to provide secondary sites of attachment to enhance their retention on tumor cells. Analogs of the peptide "GALA", an amphipathic peptide previously reported to interact with uncharged lipid bilayers, gave antibody conjugates of different molecular weight and bound peptide stoichiometry when attached to Fab fragments using the heterobifunctional cross-linker sulfo-SMCC. This attached peptide enhanced the retention and internalization of Fab fragments of NR-ML-05 on FEMX human melanoma cells, but not of NR-LU-10 on HT-29 human colon carcinoma cells, indicating that this effect might be specific for individual tumor antigen-antibody systems. This peptide appeared to increase nonspecific interactions of the conjugate with antigen-negative cells. Other membrane-active peptides were also tested. None were as effective as the "GALA" analogs. A synthetic ion channel peptide attached to NR-ML-05 Fab exhibited the greatest enhanced internalization of these tested peptides. PMID- 8431508 TI - Synthesis of protein-reactive (aminostyryl)pyridinium dyes. AB - The synthesis of two protein reactive (aminostyryl)pyridinium fluorescent dyes, N ethyl-N-[4-[2-[4-(1-methylpyridinio)]ethyl]phenyl]glycine chloride N hydroxysuccinimide ester (SuASP, 2) and 4-[4-[2-[4-(N,N- dimethylamino)phenyl]ethenyl]pyridinio]butyrate N-hydroxysuccinimide ester (ASPSu, 3), is reported. Both form amide linkage through the activated succinimidyl ester with primary amines. The two analogues differ by the position of the pyridinium positive change relative to the activated ester. SuASP forms an amide linkage that positions the positive charge distal to the protein surface, while ASPSu places the positive charge proximal. The synthesis of SuASP utilizes a palladium coupling reaction for the arylation of 4-vinylpyridine, while the major connection for ASPSu is accomplished through an aldol condensation between 4-(N,N-dimethylamino)benzaldehyde and picoline. Both reagents are shown to label covalently bovine serum albumin. PMID- 8431509 TI - Influence of carrier on biodistribution and in vitro cytotoxicity of methotrexate branched polypeptide conjugates. AB - Methotrexate (MTX) has been conjugated to various structurally related, synthetic, branched polypeptides containing a poly(L-Lys) backbone by the aid of water-soluble carbodiimide. The average degree of MTX incorporated was found to be dependent on the size of the polymer and on the identity of the terminal amino acid residue of the side chains. Consequently the average molar substitution ratio was in the range of 4.9-72.0 MTX per carrier molecule. CD spectra of conjugates showed significant differences in solution conformation correlating with the identity of the side-chain-terminating amino acid. Polycationic conjugates XAK-MTX (X = Leu or D-Leu) assumed essentially ordered (helical) secondary structure, while the CD spectrum of the amphoteric conjugate (X = Glu) corresponded to only a partially ordered conformation in PBS. The covalent attachment of MTX to branched polypeptides results in a reduction of drug in vitro cytotoxicity influenced by the carrier structure. Conjugation to amphoteric polymers, depending on the configuration and position of glutamic acid (XAK-MTX vs AXK-MTX type conjugates) resulted in a decrease of anti-791T cell activity. However polycationic conjugates bearing L-Leu at the side chain terminal position (LAK-MTX) produced a compound with cytotoxicity only about 60 times less effective than free MTX. The biodistribution in mice has been characterized by blood clearance, whole-body retention, and tissue distribution 24 h after iv administration. Blood clearance of MTX-branched polypeptides could be significantly prolonged by incorporation of glutamic acid into the side chain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431510 TI - Generation of cytotoxic agents by targeted enzymes. PMID- 8431511 TI - Temperature-responsive bioconjugates. 1. Synthesis of temperature-responsive oligomers with reactive end groups and their coupling to biomolecules. AB - Using 3-mercaptopropionic acid (MPA) as a chain-transfer agent, the radical oligomerization of N-isopropylacrylamie (IPAAm) was carried out with varying molar ratios of MPA to IPAAm and DMF. The molecular weight of oligo-IPAAm (OIPAAm) could be controlled by the ratio of MPA to IPAAm. The OIPAAm was confirmed to average one carboxyl end group per chain. All OIPAAms samples were highly water-soluble at lower temperatures and exhibited phase separation near 32 degrees C. The optical transmittance of the OIPAAms aqueous solutions changed drastically at 32 degrees C which was independent of OIPAAms molecular weight. In aqueous solutions of OIPAAm having concentrations higher than 1 wt% and molecular weight of 6100, the oligomers were precipitated and recovered in 85 wt% yield of their original content. Further, OIPAAm was grafted to atelo collagen by activated ester-amine coupling. The OIPAAm-collagen conjugates were able to dissolved in cold water and precipitated at 34 degrees C. Temperature-responsive OIPAAm-collagen conjugates are expected to maintain native collagen functionality in the solution state, react at lower temperatures, and be easily removed from the system with small temperature increases. PMID- 8431512 TI - 1H and 13C NMR of 3-O and 4-O conjugates of dopamine and other catecholamines. AB - Dopamine and its conjugates are widely distributed among biological species and are utilized for a variety of functions. Insects metabolize dopamine for cuticle melanization and sclerotization. Among the most abundant dopamines found in the larval and pupal development stages of Manduca sexta, the tobacco hornworm, are N acetyldopamine and N-beta-alanyldopamine. In addition, glycosylated derivatives of these dopamines are found mainly in the hemolymph just prior to cuticulogenesis. The 1H and 13C NMR resonances of dopamine, its 3-O-methyl, 4-O methyl, N-acetyl, and N-beta-alanyl derivatives, norepinephrine, 4-O-(beta-D glucuronopyranosyl)dopamine, and the glycosylated products of N-beta alanyldopamine and dopamine have largely been assigned. Assignments were based on one- and two-dimensional NMR analyses of the above compounds combined with that of specifically enriched [C7-13C]dopamine. 1H NMR showed that the major glycosylated natural product isolated from M. sexta pupal hemolymph was a 3-O glycosyl derivative of N-beta-alanyldopamine. 13C NMR confirmed that the carbohydrate was D-glucose probably in a beta-linkage. 1H NMR of the aromatic ring protons provided the most definitive method to distinguish 3-O- from 4-O derivatives of dopamine. In addition, the 3-O-glucosyl conjugate of N-beta alanyldopamine had unique chemical shifts and coupling patterns compared to those of 4-O-(beta-D-glucuronosyl)- and 3-O-(beta-D-glucopyranosyl)dopamine. PMID- 8431513 TI - Copolymers of lysine and polyethylene glycol: a new family of functionalized drug carriers. AB - Poly(PEG-Lys), a new, water-soluble poly(ether urethane), derived from L-lysine and poly(ethylene glycol) was investigated as a precursor for the preparation of polymeric drug conjugates. To facilitate a wide variety of coupling chemistries, the pendent carboxyl groups of poly(PEG-Lys) were converted to other reactive functional groups (amino, hydroxyl, active ester, and aldehyde) in high yield. These reactive pendent chains were then used as anchors for the covalent attachment of penicillin V and cephradine, two clinically used antimicrobial agents. Coupling to the carrier was achieved in good yields and the chemical versatility of this system was demonstrated by the preparation of conjugates having antibiotic ligands linked via biostable or biodegradable linkages to the carrier, either directly or via a spacer. Conjugate 4, poly(PEG-Lys-penicillin V ester), was obtained by linking penicillin V to the polymer backbone via hydrolytically labile ester bonds. This conjugate exhibited activity similar to that of the parent drug against three clinically important strains of bacteria. Drug activity coincided with the release of the drug from the carrier. Hydrolytically stable cephradine-containing conjugates were prepared by three different coupling methods but showed no antibiotic activity. 14C-labeled poly(PEG-Lys) was injected into mice and its biodistribution was monitored for 48 h. The carrier showed no preferential uptake by liver, spleen, or kidney. No signs of acute toxicity were evident in mice or rats when poly(PEG-Lys) was administered iv and ip at doses up to 10 g/kg. These results indicate that poly(PEG-Lys) is a promising precursor for the preparation of soluble drug conjugates. PMID- 8431514 TI - Affinity purification and characterization of anti-Tac(Fv)-C3-PE38KDEL: A highly potent cytotoxic agent specific to cells bearing IL-2 receptors. AB - A chimeric, single chain antibody fused immunotoxin, denoted anti-Tac(Fv)-C3 PE38KDEL, was engineered and expressed in Escherichia coli. The microbially expressed anti-Tac(Fv)-C3-PE38KDEL was solubilized from inclusion bodies using guanidine hydrochloride, and subsequently refolded in a redox buffer via thiol/disulfide exchange. The recombinant immunotoxin from the crude extract was purified employing receptor-affinity chromatography, which is based upon biological function and involved the immobilized p55 subunit of human IL-2 receptor. The cytotoxic activity of this immunotoxin was measured by the IL-2 dependent phytohemagglutinin (PHA) blast proliferation inhibition and HUT-102 protein synthesis inhibition assays, in which the IC50 values were 41.5 and 0.8 pM, respectively. The biochemical homogeneity and authenticity of the purified material were determined by gel permeation chromatography, amino acid composition and N-terminal sequence analyses, SDS-PAGE, isoelectric focusing, and Western blotting. The receptor-affinity-purified immunotoxin was shown to be highly effective in specifically killing cells bearing IL-2 receptors. Anti-Tac(Fv)-C3 PE38KDEL is a powerful immunosuppressant which may be a potentially useful therapeutic agent in the prevention of allograft rejection and in the treatment of autoimmune diseases. Another anticipated application of this fusion protein is as a chemotoxin in the treatment of some forms of cancer. PMID- 8431515 TI - Radioiodination of proteins using N-succinimidyl 4-hydroxy-3-iodobenzoate. AB - N-Succinimidyl 4-hydroxy-3-[131I]iodobenzoate ([131I]SHIB) was synthesized from 4 hydroxybenzoic acid in two steps. The overall radiochemical yield was 40-56%. A monoclonal antibody (mAb) was labeled in 10-15% yield by reaction with [131I]SHIB. The specific binding of [131I]SHIB mAb to tumor homogenates in vivo was 78 +/- 3%, compared to 84 +/- 3% for the same mAb labeled using N succinimidyl 3-[125I]iodobenzoate ([125I]SIB). Paired-label studies in normal mice demonstrated similar tissue distributions of 131I and 125I except in thyroid. In thyroid, uptake of the two isotopes was similar on day 1; however, 131I levels increased gradually to 2-3 times those of 125I by day 6. Our results indicate that loss of label in vivo from mAbs labeled using SHIB is somewhat higher than seen with SIB but significantly lower than that observed when direct iodination methods are used. PMID- 8431516 TI - Synthesis and characterization of a trigalactosylated bisacridine compound to target DNA to hepatocytes. AB - We have synthesized three bisacridine intercalators containing a galactose residue(s) to target DNA to cell surface receptors for use in gene-delivery systems. Each of the bisacridines could intercalate into DNA with micromolar dissociation constants. Bisacridines containing a single galactose on either a three- or six-carbon spacer from the secondary amine of spermidine-bisacridine could mediate binding of DNA to the soluble galactose receptor Ricinus communis lectin (RCA I), but not to the asialoglycoprotein receptor on primary hepatocytes. A trigalactosyl dilysyl bisacridine [(Gal-6)3Lys2-bA] compound could mediate the binding of DNA to both the ricin lectin and to primary hepatocytes. Binding of the (Gal-6)3Lys2-bA-DNA to the hepatocytes could be blocked by asialoorosomucoid. On the basis of luciferase expression, (Gal-6)3Lys2-bA did not induce transfection of the hepatocytes when attached to the pCLUC4 plasmid encoding the firefly luciferase gene. PMID- 8431517 TI - Specific recognition of antibody-oligonucleotide conjugates by radiolabeled antisense nucleotides: a novel approach for two-step radioimmunotherapy of cancer. AB - One of the major challenges in radioimmunotherapy is the specific delivery of radioisotopes to tumor cells while minimizing normal tissue radiation. In this respect, the application of two-step pretargeting schemes generally leads to more favorable tumor to normal tissue uptake ratios than direct administration of radioimmunoconjugates. In this study, we present the specific hybridization of complementary DNA fragments as a novel recognition mechanism in pretargeting. Briefly, our strategy involves first administration of antibody-DNA conjugate, followed by targeting with radiolabeled complementary DNA (antisense DNA). Complementary oligodeoxynucleotides (14-mers, Tm = 57 degrees C), in which part of the phosphodiesters has been replaced by methylphosphonates (to ensure stability against nucleases), were prepared on a DNA synthesizer. The oligonucleotides were further derivatized via a uridine moiety at their 5'-end in such a way that radiolabeling or conjugation with antibodies could be accomplished. Both a murine IgG (anti-hCG) and the human anti-tumor IgM 16.88 were conjugated with one to three oligonucleotides via the heterobifunctional cross-linker SMCC. Incubation of these immunoconjugates with the radiolabeled antisense DNA revealed specific hybridization with the antibody-linked oligonucleotides. Antigen binding studies performed with antigen-coated matrices showed that the immunoreactivity of the antibody-DNA conjugate is preserved. Moreover, it is demonstrated that the radiolabeled DNA is still capable of hybridizing selectively with the oligonucleotides of the immunoconjugate, when the latter is bound to its antigen. PMID- 8431518 TI - Order of human hematopoietic growth factor and receptor genes on the long arm of chromosome 5, as determined by fluorescence in situ hybridization. AB - A large number of human hematopoietic growth factor and growth factor receptor genes are localized at the long arm of chromosome 5. In this study we have determined the order of the human interleukin-3 (IL3), IL4, IL5, IL9, granulocyte macrophage-colony stimulating factor (GMCSF), and the MCSF receptor (MCSFR) genes by fluorescence in situ hybridization. Genomic lambda-clones were isolated using polymerase chain reaction (PCR)-generated probes and labeled with biotin and/or digoxigenin. These clones were first individually mapped: IL3, IL4, IL5, IL9, and GMCSF to 5q31 and MCSFR to 5q33. For ordering purposes multiple probe combinations were hybridized to metaphase chromosomes and interphase nuclei. The interphase hybridizations were evaluated by image analysis, which also allowed the measurement of the physical distance between the hybridization spots. These mapping results suggest the gene order 5cen-IL3/GMCSF-IL5-IL4-IL9-MCSFR+ ++-qter. The known genomic distance between the IL4 and IL5 genes allowed the estimation of the physical distances between the 5q31-specific genes, demonstrating that they are all within about 1.5 Mb of DNA. PMID- 8431519 TI - Effects of chemotherapeutic and immunosuppressive drugs on the production of erythropoietin in human hepatoma cultures. AB - The effects of agents used in combination chemotherapy were studied on erythropoietin synthesis in cultures of the human hepatoma cell line, HepG2. Erythropoietin was measured by radioimmunoassay in the culture media after 24-h treatment periods. The RNA synthesis-inhibiting drugs daunorubicin, cyclophosphamide, ifosfamide, and cis-diamine-dichloroplatinum produced a dose dependent decrease of the production of erythropoietin. Inhibition was also induced by the tubulin-binding agents vincristine and colchicine and the immunosuppressive agents azathioprine and cyclosporin A. The DNA synthesis inhibiting drugs methotrexate and cytosine arabinoside, the antimycotics 5 fluorocytosine and amphotericin B, and glucocorticoids did not inhibit. Viability studies showed that the inhibition of erythropoietin production was partly correlated with cytotoxicity. These data could be relevant with respect to recombinant erythropoietin replacement therapy in tumor-associated anemia. PMID- 8431520 TI - Oral idarubicin--an anthracycline derivative with unique properties. AB - Idarubicin belongs to a group of anthracyclines in which the methoxyl group in position 4 of the D ring in the aglycone moiety is replaced by a hydrogen atom. Lipophilicity is increased compared with other anthracyclines; as a result, idarubicin is the first anthracycline that can be administered orally while at the same time retaining its antitumor activity. In addition, the lipophilicity enables the transition of the substance, especially of the metabolite, to the cerebrospinal fluid. The metabolite idarubicinol is formed in high concentrations; this is particularly true with oral administration. Compared with all other anthracyclines, it has a very long half-life. It is the first anthracycline metabolite to have the same cytotoxic activity as the parent compound. The cardiotoxicity of idarubicin, being lower than that of other anthracyclines at equally effective doses, is even more reduced with oral administration. Preclinical and clinical experiences with oral idarubicin are reviewed. PMID- 8431521 TI - Interleukin-9 stimulates the proliferation of enriched human erythroid progenitor cells: additive effect with GM-CSF. AB - In the study we report here we investigated the colony-stimulating activities of interleukin-9 (IL-9). In the presence of erythropoietin, IL-9 was found to stimulate the proliferation of relatively early erythroid progenitor cells (BFU E) from normal human bone marrow cells depleted of mononuclear phagocytes and T lymphocytes. Neutralization experiments demonstrated that the observed BFU-E stimulating effect was not the result of intermediate production of IL-3 or GM CSF by residual accessory cells in response to IL-9. Accordingly, the effects of IL-9 were preserved when cell suspensions were further depleted of accessory cells using CD34 enrichment of progenitor cells. Furthermore, IL-9 did not stimulate bone marrow mononuclear cells to express mRNA for IL-3, GM-CSF, EPA (erythroid-promoting activity), or IL-4, as determined by a cDNA-PCR method. IL-9 is likely to act on a subpopulation of IL-3-responsive erythroid progenitor cells that are not stimulated by GM-CSF, since plateau concentration of IL-9 and GM-CSF had additive effects on BFU-E formation, whereas a combination of IL-9 and IL-3 did not. In addition to its burst-promoting activity, IL-9 was found to have a modest stimulatory activity on myeloid progenitor cells (CFU-GM) in some experiments, suggesting that this effect may be donor related. PMID- 8431522 TI - Thalassemia intermedia: compound heterozygous beta zero/beta(+)-thalassemia and co-inherited heterozygous alpha(+)-thalassemia. AB - The relative excess of alpha- over beta-globin chains in the erythroid precursors is the chief pathophysiological factor of homozygous beta-thalassemia. The clinical picture is usually characterized by a transfusion-dependent dyserythropoietic anemia (thalassemia major). However, some patients present with moderate anemia that does not require regular blood transfusions (thalassemia intermedia). The molecular heterogeneity of beta-thalassemia mutations and changes of alpha- and gamma-globin gene expression play an important role in modifying the clinical phenotype. We report here on a female Greek patient with homozygous beta-thalassemia but normal growth and development, excellent exercise tolerance, and no need of blood transfusions. She is thus mildly affected clinically, although there is marked pallor, jaundice, and hepatosplenomegaly. These signs correspond to her marked hypochromic, microcytic anemia with erythroid hyperplasia of the bone marrow. beta-Globin genotyping shows here to be compound heterozygous for the codon 39 C-->T beta zero-nonsense mutation and for the T-->C beta(+)-mutation at position 6 of the splice consensus at the exon 1/intron 1 junction (CD39 C-->T/IVS1-6 T-->C). alpha-Globin gene mapping demonstrates the presence of a 3.7-kb alpha (+)-thalassemia deletion on one allele (-alpha 3.7/alpha alpha). Taken together, this study identifies a complex interaction of genetic factors that do not significantly alter the clinical phenotype when present alone but ameliorate the course of homozygous beta thalassemia when inherited in combination. PMID- 8431523 TI - Spurious macrocytosis associated with non-Hodgkin's lymphoma: report of two cases. AB - We report two rare cases of spurious macrocytosis (SM) associated with non Hodgkin's lymphoma caused by cold agglutinin. SM was reversed, accompanied by the regression of lymphoma in case 1 but not in case 2, where the lymphoma was refractory to the chemotherapy. It is strongly suggested that lymphoma cells were related to the production of cold agglutinin and the cause of SM. PMID- 8431524 TI - Atypical chronic myelogenous leukemia in a patient with trisomy 8 mosaicism syndrome. AB - A 17-year-old woman was admitted for bone marrow transplantation with the diagnosis of atypical Philadelphia-negative chronic myelogenous leukemia (aCML), cytogenetically characterized by trisomy 8 as the sole chromosome aberration. A striking feature was a congenital opacity of the right cornea. Chromosomal analysis of skin fibroblasts were performed and revealed a mosaic for trisomy 8. Commonly, a distinct clinical picture leads to the diagnosis of trisomy 8 mosaicism syndrome (T8ms), but an extreme phenotypic variability has been observed. To our knowledge the development of an aCML in a patient with T8ms has not been reported. A review of the literature revealed that an association to other hematological disorders had been described in two cases. The question of whether our patient's aCML was a random event or not is discussed. The patient is now 24 months post transplant and shows no evidence of disease. Her Karnofsky score is 100%. We conclude that it might be worthwhile to look for an associated constitutional trisomy 8 mosaicism in all patients with trisomy 8 leukemia. PMID- 8431525 TI - Norwegian case-control study testing the hypothesis that seafood increases the risk of thyroid cancer. AB - The hypothesis that consumption of seafood increases the risk of thyroid cancer has been tested by means of a matched case-control study. Linking the file of the National Health Screening Service (NHSS) containing dietary information about 60,000 Norwegians with the 1955-89 thyroid-cancer file of the Cancer Registry, by means of the 11-digit person-number, resulted in 92 cases--each of whom was matched with five controls with regard to age, gender, and place of residence. Forty-eight cases had answered questions on diet before diagnosis; 44 did so after diagnosis. Exposure data on seafood and seafood-related vitamins were recovered from the NHSS files for all 552 subjects. Odds ratios (OR) were computed by means of conditional logistic regression analysis. Univariate analysis of the 48 sets in which the case had answered the dietary questionnaire prior to the thyroid cancer diagnosis, as well as of all 92 sets, indicate that regular users of cod-liver oil, fish liver, or fish sandwich-spread run a higher risk of thyroid cancer than irregular and nonusers, and people eating more fish dinners per week also run a higher risk of thyroid cancer. Stepwise regression analysis corroborates the study hypothesis by showing that these two seafood variables increase the risk of thyroid cancer significantly. On the other hand, the results of a simultaneous regression analysis of these two seafood variables and a dietary vitamin-D index-variable tend to reduce the tenability of the above mentioned conclusion since none of the OR estimates (all greater than one) reached significance in this part of the statistical analysis. PMID- 8431526 TI - Correlation between the prevalence of gastritis and gastric cancer in Japan. AB - To verify the hypothesis that chronic atrophic gastritis (CAG) is a precancerous lesion for gastric cancer, we investigated the correlation between the prevalence rates for CAG determined by levels of serum pepsinogens (I and II) of randomly selected, healthy, blood donors and the mortality rates for gastric cancer among four prefectures (Akita, Iwate, Miyagi, and Okinawa) in Japan. The prevalence rates for CAG according to a criterion that the level of pepsinogen I is below 70 ng/ml and the pepsinogen I to pepsinogen II ratio is below 3.0, were the highest in Akita for both sexes (38.8 percent in males, 37.8 percent in females) and the lowest in Okinawa (13.9 percent in males, 12.3 percent in females), where mortality rates for gastric cancer are the highest and the lowest in Japan, respectively. The correlation between the prevalence rates for CAG and the standardized mortality ratios for gastric cancer among these four prefectures was statistically significant in males (r = 0.97, P = 0.03), but less significant in females (r = 0.92, P = 0.08). These data strongly support the hypothesis that CAG is a precancerous lesion. The limitations of our cross-sectional study and the advantages of measuring the levels of serum pepsinogens in epidemiologic studies and in mass-screening programs for gastric cancer are discussed. PMID- 8431527 TI - Difficulty becoming pregnant and family history as interactive risk factors for postmenopausal breast cancer: the Iowa Women's Health Study. AB - We recently provided data from a prospective cohort study of postmenopausal women which suggested that a first livebirth at age 30 or older (cf before age 20) was associated with a twofold increased risk of breast cancer in women without a family history, but a 5.8-fold higher risk in women with a positive family history. To address the question of whether these observations reflect difficulty becoming pregnant or maintaining a pregnancy, we performed additional analyses in which the outcome of each pregnancy was considered. During five years of follow up, 620 incident cases of breast cancer were identified in the 37,105 women at risk. There was little evidence for an increased risk associated with a history of spontaneous abortion (relative risk [RR] = 1.1; 95 percent confidence interval [CI] = 0.9-1.4), nor was the risk higher among women who reported two or more spontaneous abortions in consecutive pregnancies (RR = 1.0, CI = 0.7-1.4). Although women who reported that they had tried unsuccessfully to become pregnant had only slightly and nonsignificantly elevated risks of breast cancer (RR = 1.1, CI = 0.9-1.3), a more pronounced and statistically significant association was noted in women with a positive family history (RR = 2.1, CI = 1.4-3.2). There was a strong inverse association between failure to become pregnant and parity (P < 0.0001); nearly 50 percent of the nulliparous married women reported having tried and failed to become pregnant, whereas the frequency was only 6.8 percent among married women with five or more livebirths.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431528 TI - A prospective study of cigarette tar yield and lung cancer. AB - We examined the relationship of cigarette tar yield and other cigarette-usage characteristics in current smokers to the incidence of lung cancer in a study population of 79,946 Kaiser Permanente Medical Care Program members, aged 30-89 years, who completed a detailed, self-administered, smoking-habit questionnaire during the years 1979 through 1985. Mean length of follow-up was 5.6 years. There were 302 incident lung cancers, of which 89 percent occurred in current or former smokers. The tar yield of the current cigarette brand was unassociated with lung cancer incidence (relative risk [RR] = 1.02 per 1 mg tar-yield in men, 95 percent confidence interval [CI] = 0.98-1.05; RR = 0.99, CI = 0.96-1.03 in women). However, in long-term (> 20 years) smokers, the risk of lung cancer was decreased in women who had smoked filtered cigarettes for 20 or more years relative to lifelong smokers of unfiltered cigarettes (RR = 0.36, CI = 0.18-0.75), but not in men who had smoked filtered cigarettes for 20 or more years (RR = 1.04, CI = 0.58 1.87). PMID- 8431529 TI - A hospital-based case-control study of breast-cancer risk factors by estrogen and progesterone receptor status. AB - It has been proposed that breast cancers may differ in their pathogenesis and etiology according to their estrogen receptor (ER) and progesterone receptor (PR) status. This hospital-based case-control study in Japan assessed the relationship between known and suspected breast-cancer risk factors and ER and PR status. Information on risk factors was collected from histologically confirmed breast cancer cases (n = 519) and from cancer-free controls (n = 9,506). Of 160 cases with known ER status, 58 percent were ER-positive; 38 percent of 157 cases with known PR status were PR-positive. No statistically significant differences were found between ER-positive cf ER-negative cases. However, statistically significant differences between PR-positive cf PR-negative cases were observed for number of full-term pregnancies (P = 0.01), menstrual regularity as a teenager (P = 0.024), and occupation as housewife (P = 0.036). Borderline differences were observed for age at menopause (P = 0.074), and age at menarche (P = 0.083). This study provides some evidence that etiologic distinctions may be greater between PR-positive and PR-negative breast cancers than between ER positive and ER-negative breast cancers. PMID- 8431530 TI - Occupational physical activity and risk of cancer of the colon and rectum in New Zealand males. AB - The association between occupational physical activity and risk of colorectal cancer by age and anatomic site was investigated in a study of 2,503 males with colorectal cancer registered with the New Zealand Cancer Registry during 1972-80. Occupational groups that involved high levels of physical activity or were predominantly sedentary were identified prior to analysis of the registry data. Relative to males in high physical activity occupations, males in sedentary occupations had an increased incidence of both cancer of the colon (relative risk [RR] = 1.2; 95 percent confidence interval [CI] = 1.0-1.4) and rectum (RR = 1.3, CI = 1.0-1.5). The RRs for sedentary workers were particularly elevated in the 35 44 and 45-54 year age-groups for colon cancer (RR = 1.8 and 1.5, respectively) and in the 45-54 year age-group for rectal cancer (RR = 1.5), whereas there was no increase in risk for sedentary workers in the 55-64 year age-group for either cancer site. The general increase in colon cancer incidence for New Zealand during the study period was reflected in the sedentary group, but there was no change in incidence among men in occupations involving high or intermediate levels of physical activity. There was no obvious pattern for the increased cancer risk for men in sedentary occupations by anatomic site. Current physiologic hypotheses for the effect of physical activity on colon cancer risk do not adequately explain an association of physical activity with risk of rectal cancer. PMID- 8431531 TI - Childhood leukemia in the vicinity of Canadian nuclear facilities. AB - An ecologic study was conducted to determine whether leukemia rates among children born to mothers residing in the vicinity of Ontario (Canada) nuclear facilities differed from the provincial average. Childhood leukemia mortality and incidence ratios for the period 1950 to 1987 were examined for five regions within 25 km of a nuclear facility. The nuclear facilities included a research development facility, a uranium refinery, a uranium mining and milling facility, and two nuclear-power generating stations. Overall, the observed number of leukemia deaths (O = 54) was slightly greater than expected (E = 46.1) during the period when the facilities operated, but the difference was not statistically significant (O/E = 1.17, 95 percent confidence interval [CI] = 0.88-1.53). There was no indication of a birth cohort effect, as the mortality ratios based on place of birth were not significantly greater than the mortality ratios based on place of death. In the analyses of individual facilities, CIs included the null value and were generally wide because of the small observed and expected numbers; however, in the vicinity of the nuclear generating stations, the observed relative excess of leukemia deaths (O = 36, O/E = 1.40) had a lower confidence limit that was close to the null value. PMID- 8431532 TI - Environmental factors and the etiology of melanoma. AB - In this piece, we have argued that, despite educational programs designed to prevent melanoma, the mortality and incidence rates for the disease have soared steadily. Even on the conventional interpretation of the data, just more than half of the presented cases of melanoma can be explained solely as 'sun-caused.' The conventional interpretation has little to offer by way of explaining the remainder of these cases, some of which, as we discussed earlier, involve melanomas on parts of the body not exposed to the sun. We have argued that the dominant interpretation in which increasing exposures to sunlight account for the increasing incidence of melanomas is a misleading oversimplification. To resolve the melanoma enigma in preventive health terms, it is imperative to acknowledge and to explore the implications of the important associations between the rise in the incidence of melanomas and environmental factors such as our increasing exposure to artificial light, electromagnetic radiation, and photo-sensitizing chemicals added to many processed foods and a range of medicinal drugs. Our argument has been that these environmental factors contribute to the problem either by altering body chemistry to make it more susceptible to the admittedly harmful effects associated with irregular and excessive exposure to the sun, and/or acting directly, as in the case of electromagnetic radiation, as promoters of melanoma. PMID- 8431533 TI - Who has the opportunity to screen for oral cancer? PMID- 8431534 TI - A commentary on gating of the active site of triose phosphate isomerase: Brownian dynamics simulations of flexible peptide loops in the enzyme, by R. C. Wade, M. E. Davis, B. A. Luty, J. D. Madura, and J. A. McCammon. PMID- 8431535 TI - Distribution of type I Fc epsilon-receptors on the surface of mast cells probed by fluorescence resonance energy transfer. AB - The aggregation state of type I Fc epsilon-receptors (Fc epsilon RI) on the surface of single living mast cells was investigated by resonance fluorescence energy transfer. Derivatization of Fc epsilon RI specific ligands, i.e., immunoglobulin E or Fab fragments of a Fc epsilon RI specific monoclonal antibody, with donor and acceptor fluorophores provided a means for measuring receptor clustering through energy transfer between the receptor probes. The efficiency of energy transfer between the ligands carrying distinct fluorophores was determined on single cells in a microscope by analyzing the photobleaching kinetics of the donor fluorophore in the presence and absence of receptor ligands labeled with acceptor fluorophores. To rationalize the energy transfer data, we developed a theoretical model describing the dependence of the energy transfer efficiency on the geometry of the fluorescently labeled macromolecular ligands and their aggregation state on the cell surface. To this end, the transfer process was numerically calculated first for one pair and then for an ensemble of Fc epsilon RI bound ligands on the cell surface. The model stipulates that the aggregation state of the Fc epsilon RI is governed by an attractive lipid-protein mediated interaction potential. The corresponding pair-distribution function characterizes the spatial distribution of the ensemble. Using this approach, the energy transfer efficiency of the ensemble was calculated for different degrees of receptor aggregation. Comparison of the theoretical modeling results with the experimental energy transfer data clearly suggests that the Fc epsilon RI are monovalent, randomly distributed plasma membrane proteins. The method provides a novel approach for determining the aggregation state of cell surface components. PMID- 8431536 TI - Kinetics of pore size during irreversible electrical breakdown of lipid bilayer membranes. AB - The kinetics of pore formation followed by mechanical rupture of lipid bilayer membranes were investigated in detail by using the charge-pulse method. Membranes of various compositions were charged to a sufficiently high voltage to induce mechanical breakdown. The subsequent decrease of membrane voltage was used to calculate the conductance. During mechanical breakdown, which was probably caused by the widening of one single pore, the membrane conductance was a linear and not exponential function of time after the initial starting process. In a large number of experiments using various lipids and electrolytes, the characteristic opening process of the pore turned out to be independent of the actual membrane potential and electrolyte concentration. Our theoretical analysis of the pore formation suggested that the voltage-induced irreversible breakdown is due to a decrease in edge energy when the pore had formed. After initiation of the pore, the electrical contribution to surface tension is negligible. The time course of the increase of pore size shows that our model of the irreversible breakdown is in good agreement with mechanical properties of membranes reported elsewhere. PMID- 8431537 TI - Lipid and water diffusion in bicontinuous cubic phases measured by NMR. AB - Lipid and water diffusion coefficients in bicontinuous cubic liquid crystalline phases have been determined with the NMR pulsed magnetic field gradient technique. In the monoolein-water system, a discontinuity in the variation of the water diffusion coefficient with water content is observed, which coincides with the two-phase region between the two cubic phases in this system. The degree of water association to the lipid has been determined, considering the obstruction factor for diffusion in the cubic phases. The lipid diffusion coefficient increases with increased unsaturation of the lipid, and decreases when larger amphiphile molecules like cholesterol, gramicidin-A, and lyso-oleoyl phosphatidylcholine are solubilized in the cubic phase. In a cubic liquid crystal of monoolein (MO), dioleoylphosphatidylcholine (DOPC), and water, the individual lipid diffusion coefficients have been determined simultaneously in the same sample. The diffusion coefficients of MO and DOPC differ by a factor of two, and both decrease with increasing DOPC content. The results are discussed in relation to probe techniques for measurements of lipid diffusion. PMID- 8431538 TI - Dipyrenylphosphatidylcholines as membrane fluidity probes. Pressure and temperature dependence of the intramolecular excimer formation rate. AB - We have measured the pressure dependence of the intramolecular excimer formation rate, K(p), for di-(1'-pyrenedecanoyl)-phosphatidylcholine (dipy10PC) probes in single-component lipid multilamellar vesicles (MLV) as a function of temperature. Apparent volumes of activation (V(a)) for intramolecular excimer formation are obtained from the slopes of plots of log K(p) versus P. For liquid-crystalline saturated lipid MLV (DMPC and DPPC), these plots are linear and yield a unique V(a) at each temperature, whereas for unsaturated lipids (POPC and DOPC) they are curvilinear and V(a) appears to decrease with pressure. The isothermal pressure induced phase transition is marked by an abrupt drop in the values of K(p). The pressure to temperature equivalence values, dPm/dT, estimated from the midpoint of the transitions, are 47.0, 43.5, and 52.5 bar degree C-1 for DMPC, DPPC, and POPC, respectively. In liquid-crystalline DMPC, V(a) decreases linearly as a function of temperature, with a coefficient -dVa/dT = 0.65 +/- 0.11 ml degree C-1 mol-1. Using a modified free volume model of diffusion, we show that this value corresponds to the thermal expansivity of DMPC. Both the apparent energy and entropy of activation, Ea and delta Sa, increase with pressure in DMPC, whereas both decrease in POPC and DOPC. This difference is attributed to the sensitivity of the dynamics and/or packing of the dipy10PC probes to the location of the cis double bonds in the chains of the unsaturated host phospholipids. Finally, the atmospheric pressure values of Ea and delta Sa for the four host MLV examined are shown to be linearly related. The relevance of this finding with respect to the structure of the excimers formed by the dipy10PC probes is briefly discussed. PMID- 8431539 TI - Electron diffraction studies of molecular ordering and orientation in phospholipid monolayer domains. AB - The molecular order and orientation of phase separated domains in monolayers of DP(Me)PE and DP(Me)2PE were determined by electron diffraction. Dark and bright fluorescent domains at the air-water interface were observed by fluorescence microscopy. The monolayers were transferred to Formvar coated electron microscope grids for electron diffraction studies. The positions of domains on the marker grids were recorded in fluorescence micrographs, which were used as guide maps to locate these domains in the electron microscope. Selected area electron diffraction patterns were obtained from predetermined areas within and outside the dark domains. Sharp hexagonal diffraction patterns were recorded from dark domains, and diffuse diffraction rings from bright areas in between dark domains. The diffraction results indicated that the dark domains and bright areas were comprised of lipid molecules in solid and fluid states, respectively. The orientation of diffraction patterns from adjacent locations within a dark domains changed gradually, indicating a continuous bending of the molecular packing lattice vector within these domains. Orientation directors in U-shaped DP(Me)2PE domains followed the turn of the arm; no vortex nor branching was indicated by electron diffraction. Directors branching from the "stem" of highly invaginated DP(Me)PE domains usually occurred at twinning angles of n pi/3 from the stem director, which would minimize packing defects in the development of thinner branches. Electron diffraction from local areas of individual domains proved that dark fluorescent domains were solid ones, and that pseudo-long range order existed in these solid domains. PMID- 8431540 TI - Comparison between orientational and conformational orders in fluid lipid bilayers. AB - The orientational order as determined by 2H NMR and the infrared frequencies of the C--H stretching modes of the methylene groups have been measured for several systems (POPC, POPC/cholesterol and POPE), all in the fluid phase, and then were compared; this work reveals an unexpected linear correlation between them. This experimental result shows that both measurements are essentially sensitive to a common motion, most likely trans/gauche isomerisation. This new correlation with those already found in the literature suggest that several measurements related to the hydrophobic core of the fluid bilayer describe different aspects of a universal behavior. The correlation presented here does not extend to the lipid in gel phase where slower motions affect the NMR lineshape. PMID- 8431541 TI - Solid state 13C NMR of unlabeled phosphatidylcholine bilayers: spectral assignments and measurement of carbon-phosphorus dipolar couplings and 13C chemical shift anisotropies. AB - The direct measurement of 13C chemical shift anisotropies (CSA) and 31P-13C dipolar splitting in random dispersions of unlabeled L alpha-phase phosphatidylcholine (PC) has traditionally been difficult because of extreme spectral boradening due to anisotropy. In this study, mixtures of dimyristoyl phosphatidylcholine (DMPC) with three different detergents known to promote the magnetic orientation of DMPC were employed to eliminate the powder-pattern nature of signals without totally averaging out spectral anisotropy. The detergents utilized were CHAPSO, Triton X-100, and dihexanoylphosphatidylcholine (DHPC). Using such mixtures, many of the individual 13C resonances from DMPC were resolved and a number of 13C-31P dipolar couplings were evident. In addition, differing line widths were observed for the components of some dipolar doublets, suggestive of dipolar/chemical shift anisotropy (CSA) relaxation interference effects. Oriented sample resonance assignments were made by varying the CHAPSO or DHPC to DMPC ratio to systematically scale overall bilayer order towards the isotropic limit. In this manner, peaks could be identified based upon extrapolation to their isotropic positions, for which assignments have previously been made (Lee, C.W.B., and R.G. Griffin. 1989. Biophys. J. 55:355-358; Forbes, J., J. Bowers, X. Shan, L. Moran, E. Oldfield, and M.A. Moscarello. 1988. J. Chem. Soc., Faraday, Trans. 1 84:3821-3849). It was observed that the plots of CSA or dipolar coupling versus overall bilayer order obtained from DHPC and CHAPSO titrations were linear. Estimates of the intrinsic dipolar couplings and chemical shift anisotropies for pure DMPC bilayers were made by extrapolating shifts and couplings from the detergent titrations to zero detergent. Both detergent titrations led to similar "intrinsic" CSAs and dipolar couplings. Results extracted from an oriented Triton-DMPC mixture also led to similar estimates for the detergent-free DMPC shifts and couplings. The results from these experiments were found to compare favorably with limited measurements made from pure L alpha PC. This detergent-based method for assigning spectra and for determining dipolar couplings and CSA in detergent-free systems should be extendable to other lipid systems. The resulting data set from this study may prove useful in future modeling of the structure and dynamics of DMPC bilayers. In addition, the fact that experiments utilizing each of the three detergents led to similar estimates for the spectral parameters of pure DMPC, and the fact that spectral parameter versus bilayer order plots were linear, indicate that the averaged conformation and dynamics of DMPC in the presence of the three detergents are very similar to those of pure L alpha DMPC. PMID- 8431542 TI - Subsarcomeric distribution of calcium in demembranated fibers of rabbit psoas muscle. AB - Direct measurements were made of the Ca distribution within sarcomeres of glycerinated rabbit psoas muscle fibers in rigor using electron probe x-ray microanalysis. Both analogue raster analysis and digital x-ray imaging were used to quantitate the Ca distribution along thick and thin filaments as a function of the concentration of free Ca2+. Even when corrected for the estimated contribution of Ca bound to thick filaments, the Ca measured in the region of overlap between thick and thin filaments significantly exceeded the Ca in the I band at subsaturating concentrations of free Ca2+. At saturating levels of free Ca2+, the excess Ca in the overlap region was diminished but still statistically significant. The data thus suggest that the formation of rigor linkages exerts multiple effects on the binding of Ca2+ to thin filaments in the overlap region by increasing the affinity of troponin C for Ca2+ and possibly by unmasking additional Ca2+ binding sites. The data also show that the cooperativity invested in the thin filaments is insufficient to permit the effects of rigor cross-bridge formation on Ca2+ binding to propagate far along the thin filaments into the I band. PMID- 8431543 TI - Fluorescence signals from the Mg2+/Ca2+ indicator furaptra in frog skeletal muscle fibers. AB - The fluorescent Mg2+/Ca2+ indicator, furaptra, was injected into single frog skeletal muscle fibers, and the indicator's fluorescence signals were measured and analyzed with particular interest in the free Mg2+ concentration ([Mg2+]) in resting muscle. Based on the fluorescence excitation spectrum of furaptra, the calibrated myoplasmic [Mg2+] level averaged 0.54 mM, if the value of dissociation constant (KD) for Mg2+ obtained in vitro (5.5 mM) was used. However, if the indicator reacts with Mg2+ with a two-fold larger KD in myoplasm, as previously suggested for the furaptra-Ca2+ reaction (M. Konishi, S. Hollingworth, A.B. Harkins, S.M. Baylor. 1991. J. Gen. Physiol. 97:271-301), the calculated [Mg2+] would average 1.1 mM. Thus, the value 1.1 mM probably represents the best estimate from furaptra of [Mg2+] in resting muscle fibers. Extracellular perfusion of muscle fibers with high Mg2+ concentration solution or low Na+ concentration solution did not cause any detectable changes in the [Mg2+]-related furaptra fluorescence within 4 min. The results suggest that the myoplasmic [Mg2+] is highly regulated near the resting level of 1 mM, and that changes only occur with a very slow time course. PMID- 8431544 TI - Deriving the intermediate spectra and photocycle kinetics from time-resolved difference spectra of bacteriorhodopsin. The simpler case of the recombinant D96N protein. AB - The bacteriorhodopsin photocycle contains more than five spectrally distinct intermediates, and the complexity of their interconversions has precluded a rigorous solution of the kinetics. A representation of the photocycle of mutated D96N bacteriorhodopsin near neutral pH was given earlier (Varo, G., and J. K. Lanyi. 1991. Biochemistry. 30:5008-5015) as BRhv-->K<==>L<==>M1-->M2--> BR. Here we have reduced a set of time-resolved difference spectra for this simpler system to three base spectra, each assumed to consist of an unknown mixture of the pure K, L, and M difference spectra represented by a 3 x 3 matrix of concentration values between 0 and 1. After generating all allowed sets of spectra for K, L, and M (i.e., M1 + M2) at a 1:50 resolution of the matrix elements, invalid solutions were eliminated progressively in a search based on what is expected, empirically and from the theory of polyene excited states, for rhodopsin spectra. Significantly, the average matrix values changed little after the first and simplest of the search criteria that disallowed negative absorptions and more than one maximum for the M intermediate. We conclude from the statistics that during the search the solutions strongly converged into a narrow region of the multidimensional space of the concentration matrix. The data at three temperatures between 5 and 25 degrees C yielded a single set of spectra for K, L, and M; their fits are consistent with the earlier derived photocycle model for the D96N protein. PMID- 8431545 TI - Adsorption to ice of fish antifreeze glycopeptides 7 and 8. AB - Experimental results show that fish antifreeze glycopeptides (AFGPs) 8 and 7 (with 4 and 5 repeats respectively of the Ala-Ala-Thr backbone sequence) bond onto ice prism planes aligned along a-axes, and inhibit crystal growth on prism planes and on surfaces close to that orientation. The 9.31-A repeat spacing of the AFGP in the polyproline II helix configuration, deduced from NMR studies, matches twice the repeat spacing of ice in the deduced alignment direction, 9.038 A, within 3%. A specific binding model is proposed for the AFGP and for the alpha helical antifreeze peptide of winter flounder. For AFGP 7-8, two hydroxyl groups of each disaccharide (one disaccharide is attached to each threonine) reside within the ice surface, so that they are shared between the ice crystal and the disaccharide. This provides 24 hydrogen bonds between AFGP 8 and the ice and 30 for AFGP 7, explaining why the chemical adsorption is virtually irreversible and the crystal growth can be stopped virtually completely. The same scheme of sharing polar groups with the ice works well with the alpha-helical antifreeze of winter flounder, for which an amide as well as several hydroxyls are shared. The sharing of polar groups with the ice crystal, rather than hydrogen-bonding to the ice surface, may be a general requirement for adsoprtion-inhibition of freezing. PMID- 8431546 TI - Collagen packing and mineralization. An x-ray scattering investigation of turkey leg tendon. AB - Several recent results are suggesting that the collagen packing in mineralized tissues is much less regular than in the case of other nonmineralizing collagen, e.g., rat tail tendon. To clarify this question we have investigated the molecular arrangement in mineralized and unmineralized turkey leg tendon as a model for the collagen of mineralized tissues. Using a combination of diffuse x ray scattering and computer simulation, it could be shown quantitatively that, although the collagen fibril structure is periodic in the axial direction, it is similar to a two-dimensional fluid in the lateral plane. This has important consequences for the understanding of the mineralization process, which is also discussed. PMID- 8431547 TI - Ultrastructure of the corneal stroma: a comparative study. AB - Using a high intensity synchrotron x-ray source, we have recorded diffraction over a range of angles from the corneas of a wide variety of species. The results show that the interfibrillar Bragg spacing varies from 39 nm to 67 nm, the fibril diameter varies from 24 nm to 43 nm, but in the species studied intermolecular Bragg spacing is constant (1.58 +/- 0.03 nm). Using these data, a number of other structural parameters were calculated including the interfibrillar volume, V, and the surface-to-surface fibril separation, S. Large variations were found, particularly between aquatic and terrestrial animals. We found that the parameter which appears to be most constant throughout the species was the volume fraction, that is, the proportion of the tissue occupied by the hydrated fibrils. Ignoring the volume of the stroma occupied by cells, the tissue fibril volume fraction was (28 +/- 3)% for both aquatic and land animals. The observation of a constant volume fraction led us to propose a simple model in which collagen molecules and interfibrillar glycosaminoglycans occur in a fixed ratio in all the species--thus species with narrow fibrils have fewer interfibrillar glycosaminoglycans and the fibrils are thus more closely spaced, and vice versa. This model agrees with many of the experimental data on corneal composition and on the physical properties of the tissue reported in the literature. PMID- 8431548 TI - A novel method for the observation of membrane transporter dynamics. AB - A new method is proposed for measuring the dynamic properties of a membrane transporter by means of steady-state fluxes. Any voltage-sensitive transporter will give a flow of substrate in the presence of a steady-state periodic membrane potential. The periodic steady-state flow, averaged over one period, is a flux that can be measured by traditional steady-state techniques, such as the radioactive tracer method. The average flux, solely due to the periodic field, is described by a set of Lorentzian functions that depend on the applied periodic field amplitude and frequency. The normal mode amplitudes and frequencies of these Lorentzians are model-independent parameters of the transport mechanism. Measurement of the average flux as a function of the applied periodic frequency permits determination of system relaxation times as the reciprocals of the midpoints of the Lorentzian curves, which in turn can be used to estimate individual rate constants of specific models. It was found by simulation of a six state model of the electrogenic Na+/glucose cotransporter, using published estimates of the model rate constants, that the periodic field effects can be large and rich with measurable details that can be used to study the mechanism thoroughly. The new method serves in this case to complement and expand on the information obtainable by means of the voltage clamp method. It was also found by means of simulations of a nonelectrogenic six-state cotransporter model that experimentally measurable effects are expected and that results can be used to distinguished among alternative kinetic models as well as to estimate individual rate constants. The range of dynamic information available with this method is not accessible by voltage clamp or other pre-steady-state methods presently in use. PMID- 8431549 TI - Detection of hexagonal phase forming propensity in phospholipid bilayers. PMID- 8431550 TI - Effects of time-dependent electric fields on membrane transport. PMID- 8431552 TI - Gating of the active site of triose phosphate isomerase: Brownian dynamics simulations of flexible peptide loops in the enzyme. AB - The enzyme triose phosphate isomerase has flexible peptide loops at its active sites. The loops close over these sites upon substrate binding, suggesting that the dynamics of the loops could be of mechanistic and kinetic importance. To investigate these issues, the loop motions in the dimeric enzyme were simulated by Brownian dynamics. The two loops, one on each monomer, were represented by linear chains of appropriately parameterized spheres, each sphere corresponding to an amino acid residue. The loops moved in the electrostatic field of the rest of the enzyme, which was held rigid in its crystallographically observed conformation. In the absence of substrate, the loops exhibited gating of the active site with a period of about 1 ns and occupied "closed" conformations for about half of the time. As the period of gating is much shorter than the enzyme substrate relaxation time, the motion of the loops does not reduce the rate constant for the approach of substrate from its simple diffusion-controlled value. This suggests that the flexible loops may have evolved to create the appropriate environment for catalysis while, at the same time, minimizing the kinetic penalty for gating the active site. PMID- 8431551 TI - Time courses of calcium and calcium-bound buffers following calcium influx in a model cell. AB - Fixed and diffusible calcium (Ca) buffers shape the spatial and temporal distribution of free Ca following Ca entry through voltage-gated ion channels. This modeling study explores intracellular Ca levels achieved near the membrane and in deeper locations following typical Ca currents obtained with patch clamp experiments. Ca ion diffusion sets an upper limit on the maximal average Ca concentration achieved near the membrane. Fixed buffers restrict Ca elevation spatially to the outermost areas of the cell and slow Ca equilibration. Fixed buffer bound with Ca near the membrane can act as Ca source after termination of Ca influx. The relative contribution of fixed versus diffusible buffers to shaping the Ca transient is determined to a large extent by the binding rate of each buffer, with diffusible buffer dominating at equal binding rates. In the presence of fixed buffers, diffusible buffers speed Ca equilibration throughout the cell. The concentration profile of Ca-bound diffusible buffer differs from the concentration profile of free Ca, reflecting theoretical limits on the temporal resolution which can be achieved with commonly used diffusible Ca indicators. A Ca indicator which is fixed to an intracellular component might more accurately report local Ca concentrations. PMID- 8431553 TI - Generation of somatic cell hybrids capable of proliferating and secreting human monoclonal antibody without any growth factor supplements. AB - A novel cell line called Trioma, which can proliferate and secrete a human monoclonal antibody in the basal medium, was established. Trioma was generated by somatic cell hybridization with human x human hybridoma and A431c, which is a cell line able to grow autonomously in the basal medium. A Trioma called TriH8 has been kept growing in the DMEM/F-12 medium for over 1 year and stably producing stomach cancer-reactive human IgM into culture medium at 10 micrograms/ml. TriH8 has a characteristic cytological phenotype, that is, to diminish cell growth in the presence of epidermal growth factor. PMID- 8431554 TI - Glycosylation of human IgG subclass and mouse IgG2b heavy chains secreted by mouse J558L transfectoma cell lines as chimeric antibodies. AB - Oligosaccharide profiles for monoclonal chimeric mouse-human and mouse IgG2b antibodies produced in the mouse J558L cell line have been determined. These chimeric antibodies share the same mouse light chain and VH region and have a single, complex, oligosaccharide moiety attached to residue 297 of the heavy chain. Since the panel of chimeric antibodies included each of the human IgG subclasses and a set of IgG3 proteins having single residue differences, it was possible to evaluate the contributions of the protein template, the cell line, and the culture conditions to glycosylation. The study shows that the J558L cell line glycosylates human heavy chains with oligosaccharides characteristic of mouse immunoglobulins. This includes a galactose alpha 1-->3 galactose structure not found in human IgG and for which most humans have naturally occurring "anti Gal" antibodies. The extent of galactosylation was very dependent on the culture conditions and was maximal for still culture. The findings have significance for the production of antibodies for in vivo administration. PMID- 8431555 TI - In vitro primary immunization of B lymphocytes for producing human monoclonal antibodies against tumor-associated antigens. AB - The selective cytotoxicity of the lysosomotropic leucine methyl ester and its lysosomal condensation product leucyl-leucine methyl ester have been used to investigate their effect on a range of lymphocyte subsets and on the cellular proliferation and secretion by immunoglobulin-secreting B cells from axillary regional draining lymph nodes of breast cancer patients. CD2+, CD3+, and CD8+ lymphocyte subsets were selectively reduced by the leucyl-leucine methyl ester treatment (CD2: 84.2-67.5%; CD3: 76.1-62.3%; and CD8: 8.0-3.4%), but there was no significant reduction in the CD4+ and CD19+ subsets (CD4: 68.2-64.7%; and CD19: 22.6-33.2%). In the presence of mouse splenic macrophages as antigen-presenting cells, rIL-2, IFN-gamma, and pokeweed mitogen-stimulated lymphocyte supernatant, leucyl-leucine methyl ester-treated lymphocytes showed a significant increase in 3H-thymidine incorporation and in the number of immunoglobulin-secreting B cells following coculture with the breast tumor cell line MCF-7. In this study, we have characterized some of the cellular and cytokine factors that are necessary for in vitro immunization of human B lymphocytes. Hopefully, this will enable human MAbs to be produced in vitro against tumor-associated antigens. PMID- 8431556 TI - The effects of hybridoma growth factor in conditioned media upon the growth, cloning, and antibody production of heterohybridoma cell lines. AB - Interleukin 6 (IL-6)/hybridoma growth factor (HGF) has been shown to be the requirement for growth of murine hybridomas in vivo or in vitro. In this paper, two kinds of conditioned media (CM) from the culture supernatants of a human fibroblast cell line CRL1506 and a cloned Epstein-Barr virus (EBV) transformed human lymphoblastoid cell line (LCL) N23 were found to have IL-6 activity by strongly promoting the growth, antibody secretion (increase of one- to three fold), and cloning efficiencies of heterohybridomas secreting human monoclonal anti-hemorrhagic fever with renal syndrome virus antibodies and LCL. Since these CM contained no detectable IL-2, and IL-4 had no effects on the growth of the cell lines, IL-6 was considered to be the main active component of the CM responsible for promoting hybridoma growth. This effect was further confirmed by IL-6-dependent cell line 7TD1 bioassay (IL-6 activity in the CM ranging from 1,000 to 10,000 units/ml). Moreover, we successfully established four EBV transformed lymphoblastoid cell lines at single-cell level by adding an equal volume of CRL1506-CM to 10% FCS-RPMI1640 in limiting dilution. Finally, it is worth noting that the sensitivity of the heterohybridomas to the two kinds of CM was not the same and was not consistent with that of their parental myeloma cell lines. Thus, it suggests that the CM might contain more than one factor, and the choice of proper conditioned media should be very useful for human monoclonal antibody production. PMID- 8431557 TI - Pilot study of anti-lipopolysaccharide human monoclonal antibody MAB-T88 in patients with gram-negative sepsis. AB - MAB-T88 is a human monoclonal IgM antibody directed at the lipopolysaccharide of gram-negative bacteria. A protocol was designed to identify a group of septic patients with a very high likelihood of gram-negative bacteremia. All 6 patients entered in the protocol had a gram-negative source, and 4 of 6 had gram-negative bacteremia. In this patient population, MAB-T88 was shown to be safe with an effective half-life of 19.1 hours. PMID- 8431558 TI - Activity enhancement of a lung cancer-associated human monoclonal antibody HB4C5 by N-deglycosylation. AB - It has been known that the lung cancer-associated human monoclonal antibody HB4C5 comprises two lambda light chains of 30 and 32 kD and that the 30 kD species is exclusively responsible for the antibody activity. This study demonstrates that the two light chains were both N-glycosylated with glycosyl residues of different sizes, one of which was sensitive to neuraminidase and the other insensitive. Our unpublished data of DNA sequence for the light chain of this monoclonal antibody indicated that the light chain contains only one possible site for N glycosylation, which located in the CDR-1. N-Deglycosylation of this monoclonal antibody under the denaturing condition resulted in the complete conversion of the two light chains into one identical polypeptide chain of 26 kD. Activity of this monoclonal antibody was found to be significantly enhanced by N deglycosylation. All the facts described above consistently indicate that the activity of this monoclonal antibody is interfered with by the attachment of bulky glycosyl residues at the antigen binding site on the light chain. The N deglycosylated antibody was stable under the storage conditions employed, suggesting that the glycosyl residues attached to the light chain do not play any important biological role except for interference with the antibody activity of binding antigen. PMID- 8431559 TI - Autologous platelet-rich plasma in cardiac surgery: aesthetics versus virtue. PMID- 8431560 TI - The effects of propofol compared to high-dose fentanyl anesthesia on rheologic parameters in coronary artery surgery. AB - Propofol has previously been found to decrease hematocrit values. Because hematocrit is an important determinant of blood viscosity, lower hematocrits may cause a decrease in blood viscosity, improving blood flow and oxygen delivery. This phenomenon may be beneficial in certain intraoperative situations. To study the influence of two anesthetic techniques on a variety of rheologic parameters, 32 patients scheduled for coronary artery bypass grafting (CABG) were divided into two groups. Group I (n = 18) was induced with high-dose fentanyl anesthesia (100 micrograms/kg), and group II (n = 16) with a combination of propofol and fentanyl anesthesia (1 to 1.5 mg/kg and 35 to 50 micrograms/kg, respectively). Maintenance anesthesia continued with infusions of the same drugs. Blood and plasma viscosity, hematocrit, erythrocyte aggregation factor, and erythrocyte deformability were measured preoperatively, intraoperatively, and up to 48 hours postoperatively. Whole blood viscosity was corrected to a standard hematocrit of 0.45. The two groups were comparable with respect to age, bypass duration, blood loss, urine output, transfusions, and fluid management. Erythrocyte deformability did not decrease during or after cardiopulmonary bypass (CPB). In both groups, hematocrit and blood and plasma were decreased significantly during and after CPB (P < 0.01) and returned to baseline levels 48 hours after surgery. After induction and before CPB, blood viscosity was only decreased in group II. However, the corrected blood viscosity was significantly elevated at all shear rates in group II compared to group I at 24 and 48 hours postoperatively (P < 0.01). In group II at these sampling times, this parameter was also significantly elevated compared to preoperative values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431561 TI - Pro: one-lung ventilation is best accomplished with the Univent endotracheal tube. AB - Over the years, thoracotomy has changed from a procedure that prompted major concern over cross-contamination caused by infection to pulmonary tumors. Assisting the thoracic surgeon by providing OLV is one of the most specialized skills an anesthesiologist can offer. This must be done in a safe, easy, and efficient manner. The Univent tube appears to be a hybrid, combining the best qualities of both the DLT and the single-lumen endotracheal tube with separate Fogarty-like catheter. The Univent tube is a technical improvement over separate endobronchial blocking catheters because its blocker shaft is attached to the main tube and, therefore, displacement is less likely. In addition, the Univent's axial blocker shaft has a lumen that provides for irrigation, suction, oxygen insufflation, CPAP, and HFV. Though equally as effective as the DLT in treatment of intraoperative hypoxemia, the Univent tube presents a unique advantage in the areas of aspiration prevention, prolonged intubation without tube exchange, and selective blockade of lung segments. The Univent tube is also easier to insert and has fewer associated risks compared to the DLT. Is it my purpose to suggest that because the Univent tube is equal to, or better than, the DLT in many areas, we should abandon the use of DLTs? Definitely not. Double-lumen tubes have performed well in the past and will continue to offer specialized functions, such as postoperative independent lung ventilation in single-lung transplant recipients. As with the acquisition of any new medical skill, the use of the Univent tube has a learning curve. It is worth the time and effort to learn to use the Univent tube.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431562 TI - Con: the Univent tube is not the best method of providing one-lung ventilation. AB - The Univent tube is a new form of bronchial blocker and is an addition to the armamentarium of the anesthesiologist for managing thoracic surgical cases. As with any new equipment/technique it will require time until the exact indications for its use become clear. The preference of anesthesiologists has oscillated between bronchial blockers and DLTs for the past 50 years, and no overall "best" method of providing OLV has yet been found. Anesthesiologists will continue to use, and to need to know how to use, DLTs for the foreseeable future. PMID- 8431563 TI - An unusual chest x-ray. PMID- 8431564 TI - Sick sinus syndrome in a teenager treated with idarubicin. PMID- 8431565 TI - Use of transesophageal echocardiography for placement and testing of an automatic implantable cardiac defibrillator. PMID- 8431566 TI - Inflation of the balloon on a pulmonary artery catheter may facilitate withdrawal. PMID- 8431567 TI - Use of Wallace catheters for central vein cannulation in patients with corrected congenital heart disease. PMID- 8431568 TI - Generalists versus subspecialists. PMID- 8431569 TI - Subspecialty training in anesthesia. PMID- 8431570 TI - Methylprednisolone does not influence endotoxin translocation during cardiopulmonary bypass. AB - This study investigated whether the prophylactic administration of methylprednisolone sodium succinate (MPSS) could prevent an increase in plasma endotoxin levels during cardiac surgery with cardiopulmonary bypass. MPSS (1 g/patient) or saline was given intravenously with induction in the steroid (n = 6) and control (n = 7) groups, respectively. Blood samples were collected preinduction and postinduction, during and after cardiopulmonary bypass, and 1 and 24 hours postoperatively. Plasma endotoxin was determined by a chromogenic Limulus amebocyte lysate assay. There was an intraoperative increase in the level of plasma endotoxin that occurred primarily after initiation of cardiopulmonary bypass and removal of the aortic cross-clamp. Endotoxin at 1 and 24 hours postoperatively was lower than the peak intraoperative levels and approached the preinduction level in both groups. The pump prime and other administered fluids contained low levels of endotoxin that were at or below the preinduction or postinduction level of the patients. MPSS did not prevent or attenuate the degree of endotoxemia during cardiopulmonary bypass. The loss of normal gut mucosal barrier function during cardiopulmonary bypass may result in endotoxemia and/or bacterial translocation, either of which could initiate or contribute to postoperative complications. PMID- 8431571 TI - Diazepam's effect on systemic vascular resistance during cardiopulmonary bypass is not caused by its vehicle (alcohol-propylene glycol). AB - Control of hemodynamic parameters during cardiopulmonary bypass (CPB) is a desirable goal of the anesthesiologist. Diazepam is known to reduce systemic vascular resistance (SVR) during CPB. This study tested the hypothesis that diazepam reduces SVR during CPB through the action of its vehicle, alcohol propylene glycol (APG). The study protocol was approved by the Institution's Human Experimentation Review Board and all patients gave informed consent. Premedication, induction, and maintenance of anesthesia were standardized. Thirty consecutive patients undergoing nonemergent cardiac surgical procedures were randomized to receive a standardized amount of diazepam, diazemuls, or alcohol propylene glycol during stable CPB. SVR in the diazepam group decreased significantly (1,242 to 968 dyne.s.cm-5, P < 0.05) compared to baseline; whereas there was no significant change in SVR in the diazemul group, and a statistically significant increase in SVR (1,217 to 1,537 dyne.s.cm-5, P < 0.05) in the APG group. It is concluded that diazepam reduces SVR during CPB. Diazepam's vehicle does not reduce SVR during CPB, and is in fact associated with an increase in SVR. PMID- 8431572 TI - Comparison of the pharmacokinetics of methohexital during cardiac surgery with cardiopulmonary bypass and vascular surgery. AB - The aim of this study was to assess the pharmacokinetics of methohexital (ME) in major vascular surgery (VASC) and to compare these data with the pharmacokinetics of ME during hypothermic cardiopulmonary bypass (HCPB) (temperature: 28 degrees C) and normothermic cardiopulmonary bypass (NCPB) (temperature: 37 degrees C). An ME bolus (2 mg/kg) was administered to 8 VASC patients at the start of surgery and to 11 HCPB patients and 11 NCPB patients at the start of cardiopulmonary bypass (CPB). Twenty-one arterial blood samples were withdrawn over the following 24 hours for ME assays. All of the patients were given similar anesthesia (fentanyl, diazepam) and muscle relaxation (pancuronium). In the VASC group, ME total body clearance (TBC) was 6 +/- 2 mL/kg/min (mean +/- SD), which is less than in previous studies. When comparing HCPB and NCPB groups, elimination half life (T1/2), TBC, volume of distribution (VD), area under the curve (AUC), and mean residence time (MRT) were similar. When comparing VASC and CPB patients, TBC and VD were greater in CPB patients than in VASC patients; thus, T1/2 (equal to 0.693 x VD/TBC) was similar. AUC was smaller in CPB patients because of hemodilution, but MRT was similar. It is concluded that ME clearance is lower in patients undergoing major vascular surgery than in healthy patients. The temperature and the duration of CPB do not seem to substantially influence the pharmacokinetics of ME when a bolus is administered. Parameters such as AUC, TBC, and VD appear modified by hemodilution during CPB; however, T1/2 and MRT, which allow comparisons between CPB and non-CPB patients, were similar in these patients. PMID- 8431574 TI - Influence of acute preoperative plasmapheresis on platelet function in cardiac surgery. AB - Withdrawal of autologous plasma offers the possibility of improving patients' hemostasis and of reducing homologous blood consumption in cardiac surgery. The influence of acute, preoperatively performed plasmapheresis (APP) on platelet function was investigated in elective aortocoronary bypass patients subjected to APP producing either platelet-poor plasma (PPP; group 1; n = 12) or platelet-rich plasma (PRP; group 2; n = 12). APP-treated patients were randomly compared to patients without APP (control group; n = 12). Platelet aggregation induced by ADP (concentration 0.25, 0.5, 1.0, and 2.0 mumol/L), collagen (4 microL/mL), and epinephrine (25 mumol/L) was determined by the turbidometric method before and after APP, as well as before and after cardiopulmonary bypass (CPB) until the morning of the 1st postoperative day. APP had no negative effects on the patients' aggregation parameters (maximum aggregation and maximum gradient of aggregation). The platelet counts in the withdrawn plasma were 25 +/- 10 x 10(9)/L (PPP-group) and 250 +/- 30 x 10(9)/L (PRP-group). Platelet counts were highest in the PRP-group at the end of the operation (after retransfusion of autologous plasma). After CPB, maximum aggregation and maximum gradient of aggregation were reduced in all groups (ranging from -6% to -25% from baseline values). Retransfusion of autologous plasma improved platelet aggregability significantly only in the PRP-group. By the first postoperative day, maximum aggregation and maximum gradient of aggregation recovered in all groups (including the control group) or even exceeded baseline values (ranging from +8% to +42% from baseline values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431573 TI - Clonidine premedication for coronary artery bypass grafting under high-dose alfentanil anesthesia: intraoperative and postoperative hemodynamic study. AB - The purpose of this study was to assess the efficacy of clonidine in achieving perioperative hemodynamic stability in patients undergoing coronary artery bypass grafting performed under high-dose alfentanil anesthesia. Twenty-four patients with left ventricular ejection fraction greater than 0.5 were prospectively studied in a double-blind manner; those requiring emergency procedures were excluded. They were randomized to receive either oral clonidine or placebo together with their premedication. Induction of anesthesia was achieved with 10 mg of alfentanil infused over 5 minutes followed by a continuous infusion of 60 mg/h during 1 hour, or until sternotomy, and then 30 mg/h until the end of surgery. Hemodynamic responses to noxious stimuli were treated with additional alfentanil boluses and isoflurane when these were unsuccessful. Intraoperative hemodynamic profile analyses showed a continuous increase in systemic vascular resistance and mean arterial pressure in the clonidine group from the time of skin incision until the onset of bypass, whereas the cardiac output profiles remained similar in the two groups. The number of additional alfentanil boluses was similar. Isoflurane requirements (1/11 v 4/13) were not significantly different, but only a few patients required this therapy. The postbypass hemodynamic profiles were similar. Severe hemodynamic impairment occurred in the clonidine group during warming in the postoperative period: this group showed a drop in systemic vascular resistance index (1276 +/- 347 v 1757 +/- 415 dyn.sec.cm-5.m2) that could not be compensated for by an increase in cardiac output despite normal filling pressures, causing hypotension (66 +/- 10 v 79 +/- 16 mmHg). This hemodynamic status led to greater requirements for vasoactive agents and inotropics in this group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431575 TI - Effects of fentanyl on coronary blood flow distribution and myocardial oxygen consumption in the dog. AB - Little data exist on the effects of fentanyl on coronary blood flow (CBF), myocardial oxygen balance, and the regional distribution of blood flow. These studies were designed to determine whether fentanyl had any intrinsic effects on myocardial oxygen consumption (MVO2) and blood flow distribution. In anesthetized dogs, fentanyl was administered in a dose of 50 micrograms/kg and various measurements were made at 5 and 20 minutes. After hemodynamic recovery from the fentanyl, the animals were treated with atropine to block the known vagomimetic effect of fentanyl and challenged with acetylcholine (3.5 micrograms/kg); then fentanyl (50 micrograms/kg) was again administered and measurements made at 5 and 20 minutes. In the untreated dogs at 5 minutes post-fentanyl, heart rate (HR) decreased 30% and at 20 minutes decreased 29%. Treatment with atropine essentially eliminated HR changes at both time periods. Mean arterial pressure (MAP) fell by 20% and 22% at 5 minutes and 20 minutes, respectively, in the untreated group, but when atropine was administered, MAP was observed to be intermediate between baseline and the untreated animals. Left ventricular MVO2 at 5 minutes in the untreated group was modestly but not significantly reduced. However, at 20 minutes post-fentanyl, MVO2 decreased significantly. MVO2 was essentially unchanged after atropine. Regional CBF (measured by radiolabelled microspheres) was unchanged at 5 minutes, but all layers exhibited significant reductions at 20 minutes. In the atropine group, only the LV epicardial area appeared to show decreases in flow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431576 TI - Relaxation responses of the coronary microcirculation after cardiopulmonary bypass and ischemic arrest with cardioplegia: implications for the treatment of postoperative coronary spasm. AB - Coronary arteriolar spasm may occur following cardiopulmonary bypass and ischemic arrest, resulting in impaired cardiac function. Because myocardial perfusion is principally regulated by the microcirculation, the in vitro effects of various clinically used vasodilating drugs on porcine coronary microvessels less than 200 microns in diameter were examined following cardioplegic arrest and reperfusion. After 1 hour of ischemic arrest using either crystalloid or blood cardioplegia solutions followed by 1 hour of reperfusion, microvessels were studied in a pressurized (40 mmHg), no-flow state, and imaged with a video tracking device. Vessels were preconstricted by 30% to 60% of their resting diameter using acetylcholine, and various vasodilatory agents were applied extraluminally. Responses to the beta-adrenergic receptor agonist isoproterenol and the nitrovasodilator sodium nitroprusside were minimally altered by either cardioplegia solution as compared to control. In contrast, relaxation responses to both the calcium channel antagonist nifedipine and nitroglycerin were diminished after ischemic arrest and reperfusion. Relaxation responses were similar with crystalloid or blood cardioplegia for all drugs tested. Despite its somewhat attenuated response, nifedipine remained the most potent vasodilator of those studied. It is concluded that (1) following ischemic arrest with either crystalloid or blood cardioplegia solutions, responses to sodium nitroprusside and isoproterenol were minimally altered, while responses to nifedipine and nitroglycerin were attenuated; (2) relaxation responses of coronary arterioles were not significantly different with either blood or crystalloid cardioplegia; and (3) despite a slightly decreased response after cardioplegia, nifedipine was the most potent vasodilator of coronary arterioles, and may be the best choice for treating postoperative coronary arteriolar spasm. PMID- 8431577 TI - Accuracy of pulse oximetry in children with cyanotic congenital heart disease. AB - The use of a pulse oximeter to monitor arterial oxygen saturation (SaO2) is considered accurate and reliable in the range of 90% to 100%. However, differing reports exist about the accuracy with desaturation. Thus, the suitability of pulse oximetry in desaturated patients was evaluated using a Nellcor N-100 oximeter. In 56 children with cyanotic congenital heart disease, the pulse oximeter reading was compared with the direct measurement of SaO2 by a CO oximeter OSM 3. The influence of high hematocrit values on the accuracy at low saturation was also investigated. All oxygen saturation measurements (two per child) were carried out after induction of anesthesia (ketamine, fentanyl, pancuronium) during a "steady state" before the surgical procedure. The results indicate that at low levels of saturation (SaO2 below 80%), pulse oximetry is not as accurate as at higher saturations, and overestimates the true value. Bias and precision between saturations measured by the pulse oximeter and the CO-oximeter were 5.8 and 4.8 in the group with a saturation below 80%, and 0.5 and 2.5 in the group with a saturation over 90%, respectively. Because the margin of safety for a patient is small when arterial saturation levels are under 80%, it is advisable under this condition to check the SaO2 measurements by a CO-oximeter. High hematocrit levels did not seem to be responsible for impaired accuracy of pulse oximetry at saturation values below 80%. PMID- 8431578 TI - Differences in temperature changes between pediatric and adult patients after cardiopulmonary bypass. AB - Nasopharyngeal (NPT) and rectal (RT) temperatures were continuously monitored in 51 adult or pediatric patients undergoing cardiac surgical procedures until 1 hour after the termination of cardiopulmonary bypass (CPB). The measurement also included the lowest NPT achieved and the dwelling time at that temperature on CPB, the rewarming time, the time on CPB, and the time that the chest remained opened after CPB. After the termination of CPB, the decrease of NPT (afterdrop) was significantly greater in the adult group than in the pediatric group. The mean decrease in adult patients was 1.34 +/- 0.65 degrees C versus 0.63 +/- 0.8 degrees C in pediatric patients. The combination of the NPT at the end of bypass (EndNPT), body weight times the EndNPT, and the dwelling of the lowest temperature times the EndNPT could predict 45% of the afterdrop. It is concluded that afterdrop occurs to a lesser degree in pediatric patients than in adults. This may be due to more efficient supplying of external heat to pediatric patients in whom there is a larger body surface area to weight ratio. PMID- 8431579 TI - Left atrial thrombus following liver resection with veno-venous bypass: use of transesophageal echocardiography to guide resuscitation. PMID- 8431580 TI - Transesophageal echocardiographic detection of left atrial involvement of a lung tumor. PMID- 8431581 TI - Hyperkalemia and myocardial atonia following cardioselective beta-blockade. PMID- 8431582 TI - Spontaneous hemothorax due to subacute aortic dissection. PMID- 8431583 TI - Paraplegia following aortic surgery. PMID- 8431584 TI - Case 1--1993. The role of erythropoietin in Jehovah's Witnesses requiring cardiac surgery. PMID- 8431585 TI - Perspectives on functional assessment: its use for policy making. AB - Functional assessment has the power to decide who receives care, for how much and by whom. Yet, despite its perceived value for setting public policy, these tools are often described as either flawed or formative in their development. Thus, policy-making using functional assessment could be considered premature during a time when cost and quality controls are overdue. Such a dilemma pits consumers, practitioners and researchers against policy-makers and payers as health-care decisions hang in the balance. This article presents the views of key constituencies on the readiness of functional assessment for policy-making. The discussion, focused primarily on setting health-care policy in the United States, is framed against a profile of health-care trends, within the context of the World Health Organization's International Classification of Impairments, Disabilities, and Handicaps, and with reference to the characteristics of selected tools in widespread use. These perspectives may shed light on ways to proceed for building confidence in the tools' viability for policy-making. PMID- 8431586 TI - Coping and confidence among parents of children with diabetes. AB - Sixty-two mothers and 45 fathers of children with diabetes completed questionnaires to assess their confidence to manage the disease and treatment. Implications of parental confidence for attitudes to (1) child-rearing, (2) coping and (3) perceived restrictions of the disease were considered. Mothers and fathers differed in reported child-rearing behaviours and strategies for coping. More confident fathers reported that information was helpful in coping with the disease, while more confident mothers reported that support from the family was more helpful. Predictors of children's locus of control scores differed between mothers and fathers. However, children expressed more external locus of control beliefs where parents believed their children to be more restricted. PMID- 8431587 TI - Measuring functional status of stroke patients with the Sickness Impact Profile. AB - Measuring outcome of stroke treatment has focused mostly on Activities of Daily Living. In our study we investigated the impact of stroke on the patient's daily life and the course of functional status over time. A community-based cohort of stroke patients was examined with the Barthel ADL Index and the Sickness Impact Profile at fixed intervals post-stroke. Data were compared with those of an elderly control group in the community. The scores of the stroke group on all the subscales of the SIP were much worse than in the control group. The differences were greatest for house management, recreation/pastime and mobility. While there was significant improvement of the mean Barthel score between 8 and 26 weeks post stroke, the mean SIP scores at these intervals did not change, with the exception of the subscale house management, which showed some improvement. It would appear that the impact of stroke on daily life is greatest in the fields of house management, recreation/pastime and mobility. PMID- 8431588 TI - Job perspectives in facioscapulohumeral muscular dystrophy. AB - The working career of 138 adult patients with autosomal dominant facioscapulohumeral muscular dystrophy (FSHD) was studied using a mailing questionnaire. Of 126 patients with an occupational history, the average female and male working career was 15 to 30 years, respectively. Of 61 respondents actually holding a job, only nine had adjustments for disease-related handicaps. Reaching above and below shoulder level was required in 24 jobs, although shoulder weakness is a presenting symptom of FSHD. In spite of these physical problems, 52 patients (85%) labelled their job as satisfying. The duration of their working career and the satisfaction with their work despite frequent physical problems warrant a careful vocational guidance of FSHD patients in order to prevent or postpone unemployment. Similar working career studies in patients with other neuromuscular disorders are worthwhile. PMID- 8431589 TI - Accelerated rehabilitation after proximal femoral fracture: a randomized controlled trial. AB - This randomized controlled trial compared accelerated rehabilitation after surgical treatment of proximal femoral fracture with conventional care and was conducted in a general hospital in an outer urban area. Participating were 261 sequentially admitted patients over the age of 50 years who met predetermined inclusion criteria and all were followed up until death or 4 months after fracture. Patients who were treated with the accelerated rehabilitation programme had a 20% reduction in length of hospital stay. Improved physical independence (as measured by Barthel Index) was observed after fracture in accelerated rehabilitation programme patients with limited pre-existing disability. Non nursing-home patients receiving accelerated rehabilitation were also less likely to be discharged to nursing-home care or die in hospital. Accelerated rehabilitation led to a substantial reduction in length of hospital stay with a modest short-term improvement in level of physical independence and accommodation status after discharge. PMID- 8431590 TI - The assessment of disability in patients on an acute medical ward for elderly people. AB - The level of independence in self-care was monitored weekly in 212 patients admitted over 6 months to an acute medical ward for elderly people, and documented on discharge using a standard assessment, the Barthel Index. At discharge from the admitting ward, 39% of patients were independent (Barthel score of 20), 36% were mildly dependent (Barthel 15-19), 15% were moderately dependent (Barthel 10-14), 4% severely dependent (Barthel 5-9) and 6% very severely dependent (Barthel 0-4). Approximately 80% were able to transfer, walk, were continent of urine and could wash their top half, but one-third were unable to dress or use the toilet independently. Over half were unable to bath themselves or climb stairs unaided. It is feasible to assess disability in a busy acute service this way. Information can be provided both to community services on discharge of individual patients, and to managers responsible for planning services for elderly people. PMID- 8431591 TI - Rehabilitation of elderly patients with multiple fractures secondary to falls. AB - Nine patients, 6% of admissions with orthopaedic trauma to a rehabilitation unit for elderly people, had multiple fractures secondary to falls. In our 13-month experience, all cases were female with a mean age of 83 years. The mean length of stay in hospital was 37 days. The majority of people were able to return to their own homes. Thirty per cent of people admitted from their own homes were discharged considerably more dependent. Fractures of the hip and humerus were the most common. Cardiac and nervous system diseases were common. Nervous system disease was the cause of the fall in 30% of the cases. Rehabilitation of these patients is more difficult than for those with single fractures, and a multidisciplinary approach is needed. PMID- 8431593 TI - Albatros: an innovative low-cost wheelchair. AB - A low-cost, comfortable, attractive and ergonomically optimized wheelchair, aimed at the Third-World population, was designed and built. It was field tested and the prototype modified accordingly. PMID- 8431592 TI - A comparative study of orthoplast cock-up splints versus ready-made Droitwich work splints in juvenile chronic arthritis. AB - A comparative study of a purpose-made cock-up orthoplast splint with a ready-made Camp Droitwich splint, was undertaken in 12 children with juvenile chronic arthritis involving the wrists and carpi. The splints were randomly allocated so that in half, the dominant hand received the orthoplast and in half the non dominant. Assessments of joint range, grip strength and functional activities were undertaken at 3 and 6 months after use of the splint; the durability of the splints was also assessed. Overall both splints performed their function adequately, the Camp Droitwich being preferred for comfort, but the orthoplast maintaining a slightly better joint position. PMID- 8431594 TI - Survey methods for the assessment of physical disability among children. AB - Estimates of the prevalence of physical disablement are based on results of population surveys. In investigations of this kind questionnaires are employed directed at the limitations on activities, resulting from long-term health problems including difficulty or an inability to perform activities of daily living, such as walking, dressing, reading and talking. This approach, however, is less appropriate for children, because many inabilities in young age merely indicate normal developmental phenomena. Researchers in several countries have dealt with the problem of how to obtain proper data on disability among children. This article reviews these approaches and concludes that questionnaires should reflect the significant activities which are common for children. Relevant screening items for three age groups (0-2, 3-4 and 5-7 years) are outlined. They show that in screening for disablement with children relatively general indications of disability must be accepted. PMID- 8431595 TI - Pheromone biosynthesis activating neuropeptide: from discovery to current status. AB - Sex pheromone production in females of many species of moths is controlled by a pheromone biosynthesis activating neuropeptide (PBAN), PBAN from Helicoverpa zea (Hez-PBAN) is a 33 amino acid peptide produced in the suboesophageal ganglion of both female and male moths. PBAN-like activity is widespread among Lepidoptera and is also reported from a cockroach and a grasshopper. The C-terminal pentapeptide of Hez-PBAN represents the minimum sequence with pheromonotropic activity. Another pentapeptide fragment of the molecule also has high pheromonotropic activity. Presence of PBAN-like immunoreactivity and biological activity in the corpora cardiaca suggests that it is the possible site of PBAN release. There is evidence that PBAN action on pheromone gland is mediated by a second messenger. Several possible sites of action for PBAN have been suggested in the biosynthetic pathway of pheromones. The gene for Hez-PBAN has been cloned and sequenced. Cloning of a synthetic PBAN gene into a baculovirus has been attempted. Studies to isolate and identify the receptors for PBAN as well as the metabolic fate of PBAN have been initiated. PMID- 8431596 TI - Leads for insect neuropeptide mimetic development. AB - Insect neuropeptides mediate a number of physiological processes critical for insect survival. The numerous neuropeptide sequences that have been reported present an opportunity to decipher the chemical and conformational requirements for neuropeptide-receptor interactions. Chemical and conformational requirements for activity represent a "template" from which agonist/antagonist peptide mimetics, with the potential to disrupt critical insect processes, can be developed. Information on structural requirements is presented for three neuropeptide families: the sulfakinins, pyrokinins, and leucokinin/achetakinins, including active core size, important side chains, peptide superagonists, and new data on pseudopeptide modification of the N- and C-terminal regions. Members of these peptide families have been associated with a variety of physiological activities such as myotropism, pheromonotropism, diapause induction, and diuresis in a number of insects. Spectroscopic data coupled with computer molecular dynamics/graphics studies on conformationally restricted analogs of insect neuropeptides reveal information on the active conformation adopted at the receptor site. Routes to development of peptide-mimetics from neuropeptide templates are discussed. PMID- 8431597 TI - Prospects of using Drosophila for insect neuroendocrine research. AB - Classical and in vitro approaches for the analysis of the molecular components of neuroendocrine systems often disrupt their close interaction with other bodily systems, which is a crucial aspect of their function in vivo. "Genetic dissection" is an alternative, noninvasive approach which involves the systematic generation of mutations in individual genes, followed by in vivo analysis of the phenotypic effects of altering a single protein at a time avoiding extraneous disruptions. Among insects Drosophila melanogaster is the most suitable model for this approach. This paper explores the application of genetic and molecular techniques available in Drosophila for studying its neuroendocrine system with special emphasis on the production of ecdysone and juvenile hormone. Strategies are described for the generation and identification of endocrine mutations, especially those affecting hormone synthesis and regulation. Once identified by a specific mutation, a gene in Drosophila can be cloned either by chromosomal microdissection and "chromosomal walk" or by transposon tagging. Methods for molecular analysis of the structure and function of a cloned gene and of the protein it encodes are available for further study. Alternatively, a gene can be cloned using heterologous DNA probes or oligonucleotides designed according to the amino acid sequence of a protein. Genes may also be cloned via their pattern of expression (using stage- or tissue-specific cDNA libraries or through transposon-mediated "enhancer detection." Anti-sense RNA, the replacement of the gene by in vitro manipulated versions, or mutagenesis of its endogenous copies can then be used for studying its function in vivo. Information about endocrine genes in Drosophila as well as material such as cloned genes and antibodies should be useful for the analysis of endocrine systems in other insects which are not amenable to genetic manipulations. Such information should be helpful in designing novel means for pest control based on the specific intervention with endocrine systems regulating insect development and reproduction. PMID- 8431598 TI - Chitin synthesis and degradation as targets for pesticide action. AB - Various pesticides are being used to destabilize, perturb, or inhibit crucial biochemical and physiological targets related to metabolism, growth, development, nervous communication, or behavior in pestiferous organisms. Chitin is an eukaryotic extracellular aminosugar biopolymer, massively produced by most fungal systems and by invertebrates, notably arthropods. Being an integral supportive component in fungal cell wall, insect cuticle, and nematode egg shell, chitin has been considered as a selective target for pesticide action. Throughout the elaborate processes of chitin formation and deposition, only the polymerization events associated with the cell membrane compartment are so far available for chemical interference. Currently, the actinomycetes-derived nucleoside peptide fungicides such as the polyoxins and the insecticidal benzoylaryl ureas have reached commercial pesticide status. The polyoxins and other structurally-related antibiotics like nikkomycins are strong competitive inhibitors of the polymerizing enzyme chitin synthase. The exact biochemical lesion inflicted by the benzoylaryl ureas is still elusive, but a post-polymerization event, such as translocation of chitin chains across the cell membrane, is suggested. Hydrolytic degradation of the chitin polymer is essential for hyphal growth, branching, and septum formation in fungal systems as well as for the normal molting of arthropods. Recently, insect chitinase activity was strongly and specifically suppressed by allosamidin, an actimomycetes-derived metabolite. In part, the defense mechanism in plants against invasion of pathogens is associated with induced chitinases. Chitin, chitosan, and their oligomers are able to act as elicitors which induce enhanced levels of chitinases in various plants. Lectins which bind to N-acetyl-D-glucosamine strongly interfere with fungal and insect chitin synthases. Plant lectins with similar properties may be involved in plant pathogen interaction inter alia by suppressing fungal invasion. PMID- 8431599 TI - Glutamate receptor inhibitors as potential insecticides. AB - Philanthotoxin (PhTX) is a neurotoxic constituent of the paralytic venom of the digger wasp, Philanthus triangulum. PhTX inhibits glutamate receptors of insect muscles mostly as a channel blocker, thereby producing muscle paralysis. Since glutamate receptor blockers may be of value as selective insect control agents, numerous derivatives of PhTX were synthesized and tested for their potencies as inhibitors of insect skeletal muscle glutamate receptors. Structure-activity relationship studies revealed that shortening the polyamine chain length reduced potency, and quaternarization of the nitrogen destroyed it. The potency was increased by a bulky anchoring group with moderate hydrophobicity at the end of the polyamine chain. The conversion of the tryosyl moiety to 3,5-diiodo-tyrosyl also increased potency and so did lengthening the butyryl chain from 4 to 10 carbons. Not only did PhTXs inhibit different subtypes of glutamate receptors, including the mammalian N-methyl-D-aspartate receptor, but also nicotinic receptors of insects and vertebrates. Because of this low selectively, and the hydrophilicity of the derivatives tested, which interferes with their penetration to the target receptor, these compounds cannot be used as insecticides. Nevertheless, the insect skeletal muscle glutamate receptor is a viable target for selective insecticides and major changes in PhTX structure may possibly produce derivatives that can be potential insecticides. PMID- 8431600 TI - Insect detoxifying enzymes: their importance in pesticide synergism and resistance. AB - Pyrethroid esterases of Trichoplusia ni, Spodoptera littoralis and Bemisia tabaci hydrolyze the trans-isomers of various pyrethroids more extensively than the cis isomers. Profenofos fed to T. ni larvae at a level inhibiting the gut pyrethroid esterases by 65% with trans-permethrin and of 95% with cis-cypermethrin increased the toxicity of topically applied trans-permethrin by fourfold and cis cypermethrin by 20-fold. Similar assays with S. littoralis resulted in an increase of about threefold in the toxicity of both compounds. Monocrotophos, profenofos, acephate, and methidathion inhibited pyrethroid esterase activity in B. tabaci and synergized considerably the toxicity of cypermethrin. The remarkable tolerance of the predator Chrysopa carnea to pyrethroids is attributed to the presence of a high level of pyrethroid esterase activity with a unique specificity for hydrolyzing the cis-isomer. Phenyl saligenin cyclic phosphonate, a potent inhibitor for larval pyrethroid esterases synergized the toxicity of trans-permethrin by 68-fold from an LD50 of 17,000 micrograms/g to 250 micrograms/g. In contrast, oxidase inhibitors such as piperonyl butoxide, SV-1, and MPP synergized considerably the toxicity of pyrethroids in Tribolium castaneum and Musca domestica. Hence the predominant pathway for pyrethroid detoxification in insects, whether hydrolytic or oxidative, depends largely on the insect species. The high toxicity of the recent developed acylureas results from their high retention in the insects. Assays using radiolabeled diflubenzuron and chlorfluazuron applied to fourth instar T. castaneum larvae revealed a rapid elimination of diflubenzuron (T1/2 approximately equal to 7 h) as compared with chlorfluazuron (T1/2 > 100 h). Addition of 100 ppm DEF to the diet increased both the retention time and the toxicity of diflubenzuron in both T. castaneum and S. littoralis, which was due probably to the inhibition of diflubenzuron hydrolase activity. Esterases, hydrolyzing pyrethroids, and acylureas may serve as tools for evaluating potential synergists and for monitoring resistance in various agricultural pests due to increased metabolism. PMID- 8431601 TI - Depressant insect selective neurotoxins from scorpion venom: chemistry, action, and gene cloning. AB - The present study examines the similarity in the symptoms and binding properties between the depressant and excitatory insect-selective neurotoxins, derived from scorpion venom. A comparison of their primary structures and neuromuscular effects is presented. A new depressant toxin (LqhIT2) was purified from the venom of the scorpion Leiurus quinquestriatus hebraeus. The effects of this toxin on a prepupal housefly neuromuscular preparation mimic its effects on the intact insect, i.e, a brief period of repetitive bursts of regular junction potentials (JPs) is followed by reduced amplitude JPs ending with a block of the neuromuscular transmission. "Loose" patch clamp recordings indicate that the repetitive activity has a presynaptic origin (the motor nerve) and resembles the effect of the excitatory toxin AaIT. The final synaptic block is supposed to be the end result of neuronal membrane depolarization. Such an effect is not caused by an excitatory toxin, which induces long "trains" of repetitive firing. The amino acid sequences of three depressant toxins were determined by automatic Edman degradation indicating a high degree of sequence homology. This conservation differs from those of other groups of scorpion toxins. The opposing pharmacological effects of depressant toxins are discussed in light of the above neuromuscular effects and sequence analysis. A genetic approach in the study of the structure-function relationships of the depressant toxins was initiated by isolating cDNA clones encoding the LqhIT2 and BjIT2 toxins. Their sequence analysis revealed the precursor form of these toxins: A 21 amino acid residue signal peptide followed by a 61 amino acid region of the mature toxin, and three additional amino acids at the carboxy terminus. PMID- 8431602 TI - Insect neuropeptides: discovery and application in insect management. AB - New approaches to the development of insect control agents have been revealed through the molecular description of neuropeptides, their biogenesis, action, and degradation. Prerequisite to the exploitation of a neuropeptide as a lead to control agent development is a thorough understanding of the biochemistry of the neuropeptide and appreciation of its physiological impact. Reliable bioassays must be coupled with advanced biochemical and molecular genetic technologies to overcome limitations imposed by the typically low endogenous levels of individual neuropeptides. Purification, amino acid sequencing, and gene cloning provide the molecular tools necessary for studies on neuropeptide synthesis, processing, secretion, receptor binding, and inactivation. Each of these areas consists of a number of amino acid sequence-, and enzyme-dependent steps which may be considered as targets for the development of highly specific control agents. These agents will include antagonist and superagonists, peptidomimetics, recombinant peptides delivered through the baculovirus technology, receptor blockers, and enzyme inhibitors. PMID- 8431603 TI - Morphological study of the effects of intranasal zinc sulfate irrigation on the mouse olfactory epithelium and olfactory bulb. AB - The effects of intranasal zinc sulfate (ZnSO4) irrigation on the morphology of the olfactory epithelium and olfactory bulb were studied in mice with short survival times (as early as 1 day) and with long survival times (up to 593 days) after the irrigation procedure. As in several previous studies, the olfactory epithelium was completely destroyed within a few days after the ZnSO4 treatment. Within 2-4 days, the septum and turbinates were covered by a new, cuboidal epithelium, the cells of which differed significantly from any cells normally seen in the olfactory epithelium. Slowly, over several months, small areas of the olfactory epithelium regenerated in many of the animals. The ultrastructural changes occurring in the olfactory bulb from 1 to 25 days (the reactive stage) were characterized by degenerating olfactory axons and axon terminals, hypertrophy of astroglial cell processes, and proliferation of or extravasation by phagocytic cells. By 25 days after intranasal ZnSO4 irrigation, the number of reactive glial processes and phagocytic cells returned to normal. In some mice with survival times of 150 days or longer, there was reinnervation of small areas of the olfactory bulb by regenerated olfactory axons. These new olfactory axons innervated only superficial glomeruli or the outer portions of deeper glomeruli, but they formed synaptic contacts with mitral/tufted cells and periglomerular cells that did not differ from control animals. These findings were supported by tract-tracing experiments with 3H-amino acids and by behavioral analysis. In summary, the ultrastructural changes observed in the olfactory bulb in this study were not significantly different from those observed after surgical lesions of the olfactory epithelium or nerve.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431604 TI - Tracing neural pathways in snail olfaction: from the tip of the tentacles to the brain and beyond. AB - The anatomical organization of the olfactory system of terrestrial snails and slugs is described in this paper, primarily on the basis of experiments using the African snail Achatina fulica. Behavioral studies demonstrate the functional competence of olfaction in mediating food finding, conspecific attraction, and homing. The neural substrate for olfaction is characterized by an extraordinarily large number of neurons relative to the rest of the nervous system, and by the fact that many of them are unusually small. There exist multiple serial and parallel pathways connecting the olfactory organ, located at the tip of the tentacle, with integrative centers in the central nervous system. Our methods of studying these pathways have relied on the selective neural labels horseradish peroxidase and hexamminecobaltous chloride. One afferent pathway contains synaptic glomeruli whose ultrastructure is similar to that of the glomeruli seen in the mammalian olfactory bulb and the insect olfactory lobe. All of the olfactory neuropils, but especially the tentacle ganglion, contain large numbers of morphologically symmetrical chemical synapses. The procerebrum is a unique region of the snail brain that possesses further features analogous with olfactory areas in other animal groups. Olfactory axons from the tentacle terminate in the procerebrum, but the intrinsic neurons do not project outside of it. An output pathway from the procerebrum to the pedal ganglion has been identified and found to consist of inter-ganglionic dendrites. The major challenge for future studies is to elucidate the pattern of connectivity within, rather than between, the various olfactory neuropils. PMID- 8431605 TI - Cellular organization and growth-related plasticity of the crayfish olfactory midbrain. AB - Little knowledge is available concerning the detailed anatomy of the crusctacean central olfactory pathway. We are using radiolabeling, Golgi and biocytin/neurobiotin tracer methodologies, at the correlated light and electron microscopical levels, to study the olfactory midbrain of the freshwater crayfish. We have found that primary afferent fibers from the antennular olfactory receptor cells branch extensively throughout the length of the glomerular columns within the olfactory lobes in the midbrain. Globuli cells of the lateral cell clusters ramify as dendritic arborizations within both the olfactory and accessory lobes; their axons project out the olfactory-globular tracts to the lateral protocerebrum, often branching to both sides. Developmental plasticity involving the connections made by afferent fibers within the olfactory lobes may permit detailed examination of organizational changes within the midbrain as the animal grows and adds new afferent input from the periphery. PMID- 8431607 TI - Fine structure of transverse tubules and the sarcoplasmic reticulum at the myotendinous junction of stretched muscle fibers of the rat. AB - The transverse (T) tubules and the sarcoplasmic reticulum (SR) at the myotendinous junction of stretched rat skeletal muscle were examined by conventional and intermediate voltage electron microscopy. Stretching induced a large cytoplasmic space devoid of myofibrils at the ends of lengthening fibers. In this space, irregularly running tubular elements were seen. They were connected both with subsarcolemmal caveolae and with T tubules traversing to the A-I junctional level of the preexisting myofibrils. The SR was arranged at regular intervals which were narrower than those of the adult sarcomere. This orderly spacing of the SR seems to indicate that they may play some role(s) in myofibril assembly and/or T tubule arrangement. PMID- 8431606 TI - Synaptic organization and development of the antennal lobe in insects. AB - Many insects possess a highly developed sense of smell. This paper summarizes the cellular and synaptic organization of the antennal (olfactory) lobe of the insect brain and then reviews morphological and fine-structural aspects of the development of the lobe. Visualization of synapses between classes of neurons identified by physiological, morphological, or transmitter-cytochemical properties has provided insights into arrangements of contacts and their possible roles in information processing. Studies of development have revealed the requirement for afferent axons from the antenna for the formation of olfactory glomeruli, where virtually all of the synapses in the lobe occur, and have suggested the possibility that glial cells play a role in the instructive influence of the axons on their target neurons in the lobe. The findings reviewed in this paper are primarily from one representative hemimetabolous insect, the American cockroach, and one representative holometabolous insect, a hawkmoth, and comparisons are made with vertebrate systems when appropriate. PMID- 8431608 TI - Halothane hepatitis in a renal transplant patient previously exposed to isoflurane. PMID- 8431609 TI - Low serum iron and neuroleptic malignant syndrome. PMID- 8431610 TI - Ethambutol-induced ocular toxicity revisited. PMID- 8431611 TI - Comparative studies on the in vitro drug dissolution profiles for hydroxyzine hydrochloride tablets. AB - OBJECTIVE: A significant practical problem in the standardization of dissolution testing is addressed. In vitro releasing characteristics of hydroxyzine hydrochloride tablets are presented to further the documentation of bioequivalency criteria. DESIGN: The assessment model compares the official United States Pharmacopeia disintegration approach for dissolution analysis with that of the Food and Drug Administration's recommended rotating paddle technique for inducing aqueous disruption of the solid oral dosage form. RESULTS: The rationale and significance of the study focuses attention on the variation in release of the active ingredient observed relative to the four formulation strengths. With differences in the extent of dissolution noted and official standards in mind, emphasis is placed on the development of an alternate test protocol. CONCLUSIONS: Dissolution data derived via ultraviolet spectrophotometry revealed statistically significant differences in the amount of hydroxyzine hydrochloride being released from its coated structure, the extent of which was found to be dependent on the acid nature of the simulated gastric dissolution medium used and intensity of mixing action employed. PMID- 8431612 TI - Antibiotic prescribing patterns in Italian hospital inpatients with pneumonia, chronic obstructive pulmonary disease, and urinary tract infections. AB - OBJECTIVE: The primary objective of this study was to describe the antibiotic prescribing patterns in hospital inpatients with pneumonia (PN), exacerbations of chronic obstructive pulmonary disease (COPD), and urinary tract infections (UTIs). A second objective was to verify if some selected variables (i.e., risk factors, patient age, size of hospitals) were affecting the therapeutic choice. DESIGN: Survey was performed on 1609 patients. The data were collected by physicians using a special form, covering a six-month period. SETTING: Twenty-six medical wards and 8 geriatric wards in 24 acute-care hospitals in the Veneto Region in Northern Italy. PATIENTS: A consecutive sample of PN, COPD, and UTI patients treated with antibiotics. MAIN OUTCOME MEASURES: The following information was collected: patient and hospital demographics, risk factors, diagnoses, and antibiotic regimens. RESULTS: Sixty-three antimicrobial agents used, with 2115 administrations, 1227 of which were single-drug therapy. The most frequently used drugs were third-generation cephalosporins (24.6 percent), fluoroquinolones (15.4 percent), aminopenicillins (15.0 percent), and ureidopenicillins (9.7 percent). There is great variability of therapeutic regimens in the various hospitals for the same disease. However, this variability is not explained by the different types of hospitals or by the patients' characteristics (e.g., age, risk factors). CONCLUSIONS: Our results show that the use of broad-spectrum antibiotics probably is excessive. Moreover, the treatment seems to be based more on the opinion of the treating physician and the local habits rather than objective criteria. These factors may have negative repercussions not only in economic terms, but also in terms of alteration of the bacterial ecology. PMID- 8431613 TI - Didanosine-associated eosinophilia with acute thrombocytopenia. AB - OBJECTIVE: To report a case of didanosine (ddI)-induced acute thrombocytopenia and to discuss the incidence of this occurrence. CASE SUMMARY: A 42-year-old man was admitted to the hospital on November 21, 1991, with acute thrombocytopenia. The patient had an AIDS index diagnosis of Kaposi's sarcoma (KS) in 1988 and had been taking zidovudine (ZDV) for three years without any adverse effects. On July 26, 1991, he complained of increasing fatigue and weight loss. At that time, the therapy was changed from ZDV to ddI. Over the next four months the drug therapy was altered from ddI to ZDV and ZDV to ddI because of increasing fatigue and gastrointestinal symptomatology; all of the other chronic medications were maintained at the same dosages and frequency. All laboratory work remained stable and no new active processes were found during this period. The patient developed acute thrombocytopenia upon his last change to ddI and all of the chronic drug therapy was stopped. His platelet count returned to his baseline value three weeks after the discontinuation of ddI and reinstitution of his chronic medications. DISCUSSION: A review of the literature showed two documented cases of thrombocytopenia with ddI on a dosage escalation study. CONCLUSIONS: Close patient monitoring is essential while administering ddI. PMID- 8431614 TI - Where the kidney is concerned, how much mannitol is too much? AB - OBJECTIVE: To report a case of mannitol-induced acute renal failure (ARF). CASE SUMMARY: A 31-year-old woman who had been on long-term warfarin therapy for atrial fibrillation was admitted to the hospital with hemoptysis. Following reversal of her anticoagulation, she had a tonic-clonic seizure nine days after admission. An emergency computed tomography scan revealed cerebral edema, which was initially treated with hyperventilation and steroids. Two days later, a repeat scan showed progression of the cerebral edema with midline shift. Mannitol 550 g was infused over the next 28 hours, precipitating ARF. Despite prompt hemodialysis to reverse the renal failure, the patient died. This case of apparent mannitol-induced ARF illustrates several pathophysiologic effects of this agent. DISCUSSION: Case reports in the literature discussing mannitol induced ARF are reviewed and compared. A relationship between dose and ARF and its reversal with hemodialysis is postulated. CONCLUSIONS: It is likely that sufficient doses of mannitol may lead to ARF. Limitation of dose may prevent and treatment with hemodialysis may reverse ARF in these instances. PMID- 8431615 TI - Meperidine-related seizures associated with patient-controlled analgesia pumps. AB - OBJECTIVE: To report three cases of meperidine-related seizures when meperidine was administered via patient-controlled analgesia pump (PCAP) and to review literature related to meperidine-associated seizures. DATA SOURCES: Case reports and review articles identified by a computerized search (MEDLINE) and manual search (Index Medicus). DATA SYNTHESIS: PCAPs are being used frequently to relieve the pain of sickle cell crisis as well as pain from many other etiologies. We report three cases of meperidine-related seizures associated with its administration via PCAP. Each of the patients received either relatively high doses, long-term therapy, or both. Meperidine has been associated with seizure activity when administered via traditional routes. Previously identified risk factors for the development of meperidine-related seizures include renal failure, high meperidine dosages, and coadministration of hepatic enzyme-inducing medications or phenothiazines. CONCLUSIONS: Meperidine administered via PCAP may be associated with seizures. Optimally, an alternative analgesic should be administered when this route is used. PMID- 8431616 TI - Ceftriaxone-induced acute pancreatitis. AB - OBJECTIVE: To report a case probable ceftriaxone-induced acute pancreatitis. CASE SUMMARY: A patient with a history of short-bowel syndrome on home total parenteral nutrition developed fever, chills, and right flank pain. She was diagnosed with gram-negative catheter sepsis and prescribed antibiotic therapy to be administered for four weeks. After completion of the first week of therapy, the antibiotic regimen was changed to intravenous injections of ceftriaxone to be given daily at home. Prior to discharge the patient developed acute abdominal pain, leukocytosis, jaundice, and markedly elevated lipase and amylase concentrations consistent with acute pancreatitis. The patient's condition improved upon discontinuation of the ceftriaxone and the remainder of her stay was uneventful. DISCUSSION: There is only one other case report in the literature of probable ceftriaxone-induced pancreatitis. Multiple other medications have been implicated in causing acute pancreatitis. The exact mechanism of this uncommon adverse effect of ceftriaxone is unknown. CONCLUSIONS: There was a temporal relationship between the development of this patient's signs and symptoms and the administration of ceftriaxone. We could not identify any other factors that may have been responsible for the development of her acute pancreatitis. Ceftriaxone should be considered as a possible etiologic agent in patients who present with acute abdominal pain and elevated lipase and amylase concentrations. PMID- 8431617 TI - High-dose ciprofloxacin in the treatment of a renal cyst infection. AB - OBJECTIVE: To report a case of renal cyst infection successfully treated with ciprofloxacin. CASE SUMMARY: The clinical course of a 33-year-old woman with radiologic and symptomatic evidence of a renal cyst infection continued to worsen after 7 days of apparently adequate antibiotic therapy for Escherichia coli isolated from her urine. Antibiotic therapy with intravenous ciprofloxacin 600 mg every 12 hours was administered for 7 days and then given as oral therapy (750 mg q12h) for another 14 days. The patient's clinical condition rapidly improved on ciprofloxacin and follow-up 28 days later showed no evidence of infection. DISCUSSION: Renal cyst infections are a serious complication of polycystic kidney disease and are often refractory to standard antimicrobial therapy. Ciprofloxacin has the chemical properties and antimicrobial activity needed to treat these infections. Previously reported concentrations of ciprofloxacin in renal cyst fluid are therapeutic for the common pathogens associated with renal cyst infections. CONCLUSIONS: Ciprofloxacin appears to be a safe and effective option for treating renal cyst infections. Further controlled studies evaluating its clinical efficacy are warranted. PMID- 8431618 TI - Maternal noncompliance with antibiotics during breastfeeding. AB - OBJECTIVE: To determine the incidence of antibiotic prescription failure in breastfeeding women, and to characterize breastfeeding patterns during antibiotic therapy. DESIGN: Prospective cohort study by telephone follow-up of 203 breastfeeding women who were prescribed antibiotics as monotherapy. SETTING: A teratogen/drug information service (the Motherisk Program) in a tertiary care, pediatric hospital in Toronto, Canada. MAIN OUTCOME MEASURES: Number of breastfeeding women who did not initiate the antimicrobial therapy, and breastfeeding patterns during therapy in women who started it. RESULTS: Of 203 breastfeeding women who consulted the Motherisk Program for information about the safety of antimicrobials during breastfeeding, 125 (62 percent) were followed within 32 weeks (median 11). Nineteen of the 125 (15 percent) did not initiate the antimicrobial therapy. Of the remaining 106 women, 7 (7 percent) stopped breastfeeding during therapy. Despite reassuring advice, 1 in 5 women either did not initiate therapy or did not continue breastfeeding. CONCLUSIONS: Physicians should be aware of the substantial rate of noncompliance with drug regimens among nursing women and the potential negative impact of drug therapy on breastfeeding. PMID- 8431619 TI - Gastric ulcer perforation associated with the use of injectable ketorolac. AB - OBJECTIVE: To report a case of a perforated gastric ulcer associated with the use of injectable ketorolac tromethamine. DATA SYNTHESIS: A 77-year-old woman with no previous history of peptic ulcer disease developed a perforated gastric ulcer after four days of treatment with ketorolac. To date, six other cases of gastrointestinal (GI) perforation associated with the use of ketorolac have been reported to the manufacturer. CONCLUSIONS: Although ketorolac is an effective analgesic, it is a nonsteroidal antiinflammatory agent and thus has the propensity for causing GI ulceration. Caution should be used when administering this drug and patients should be monitored for GI adverse effects. PMID- 8431620 TI - Use of cyclosporine in rheumatoid arthritis. PMID- 8431621 TI - Flumazenil in the treatment of hepatic encephalopathy. PMID- 8431622 TI - Antenatal phenobarbital to prevent or minimize intraventricular hemorrhage in the low-birthweight neonate. AB - OBJECTIVE: To review the evidence that antenatal phenobarbital can reduce the incidence or severity of periventricular-intraventricular hemorrhage (PIVH) in low-birthweight neonates. DATA SOURCES: MEDLINE searches were conducted with fan searches of all papers. STUDY SELECTION: Emphasis was placed on human data supplemented by relevant animal data. DATA SYNTHESIS: The barbiturates have been used to reduce hypoxic-ischemic cerebral events. Giving phenobarbital to high risk pregnant women allows the drug to be in therapeutic concentrations during the critical period when PIVH occurs in low-birthweight infants. Current data suggest that antenatal phenobarbital can decrease the severity of PIVH; fewer data are available stating that it can decrease the incidence of PIVH. CONCLUSIONS: Evidence supports the hypothesis that antenatal phenobarbital is effective in decreasing the severity of PIVH in low-birthweight neonates. Further data are necessary regarding the incidence of low Apgar scores and respiratory depression in neonates given antenatal phenobarbital. PMID- 8431623 TI - Antifungal prophylaxis in immunocompromised hosts. AB - OBJECTIVE: To review the literature on the efficacy and safety of antifungal agents for prophylaxis of fungal infections in populations of immunocompromised hosts (key words: hematology-oncology, surgical, solid organ transplant, HIV infection), and to develop guidelines and recommendations regarding safe and effective drug regimens for antifungal prophylaxis in this patient population. DATA EXTRACTION: Comprehensive review of clinical trials of antifungal prophylaxis published in the English literature, with an emphasis on controlled trials, and discussion of key clinical trials illustrating efficacy and safety of agents for antifungal prophylaxis in immunocompromised patients. RESULTS: Much of the clinical data evaluating the efficacy and safety of antifungal prophylaxis has been generated in cancer patients. The choice of antifungal agent for prophylaxis in this population remains controversial. However, azole compounds such as clotrimazole, ketoconazole and fluconazole appear to be more effective and better tolerated than nystatin suspension. Although ketoconazole has been shown to reduce fungal colonization in surgical patients, current data do not support the routine use of antifungal prophylaxis in this population. In renal transplant recipients, clotrimazole troches have been shown to be more effective than placebo or nystatin suspension. Selective bowel decontamination with nonabsorbable antibiotics and nystatin may be useful in reducing Candida colonization in liver transplant patients but no definitive recommendations may be made at this time regarding optimal antifungal prophylaxis in these patients. In patients with advanced HIV disease or history of prior fungal disease prophylaxis for oropharyngeal candidiasis is indicated, although the agent of choice remains controversial. Fluconazole is the drug of choice for prevention of relapse of cryptococcal meningitis in patients with AIDS. Finally, only limited data exist assessing the relationship between local colonization and systemic fungal infection. Adverse effects associated with antifungal prophylaxis, generally limited to nausea and vomiting and transient elevations in hepatic transaminases, occur with similar frequency among available oral or topical agents. However, the incidence of nausea and vomiting with resultant poor patient tolerance and compliance is usually higher with nystatin. CONCLUSIONS: Based on available data from controlled clinical trials, azole agents are currently the most effective and best-tolerated drugs for antifungal prophylaxis in immunocompromised hosts. Choice of one agent in this group over another may be dictated by cost. As new antifungal treatments are released onto the market, these drugs should be compared with existing agents in controlled clinical trials. Future studies should be designed to evaluate the relationship between local colonization and disseminated infection. PMID- 8431624 TI - Calcium-channel antagonists for prevention of atherosclerosis. AB - OBJECTIVE: To critically evaluate the current literature regarding the role of calcium-channel antagonists in preventing atherosclerosis. DATA SOURCES: English language clinical studies, abstracts, conference proceedings, and review articles pertaining to calcium-channel antagonists and atherosclerosis. STUDY SELECTION: Relevant animal and human studies examining the role of calcium-channel antagonists in atherosclerosis prevention and treatment. DATA EXTRACTION: Potential mechanisms for the development of atherosclerosis and the use of calcium antagonists for preventing and treating coronary artery disease are discussed. Animal studies are summarized; next, significant data from human clinical studies are presented. DATA SYNTHESIS: Available studies are described and discussed. CONCLUSIONS: Results from animal and clinical trials in humans suggest that calcium antagonists may retard the development and progression of atherosclerosis. However, most clinical trials to date have been conducted in patients with proven atherosclerotic plaques. Further studies examining the role of calcium-channel antagonists in preventing and treating atherosclerosis are needed, but may be difficult to conduct because of the large numbers of patients required, long trial duration, and associated costs. PMID- 8431625 TI - Assessing the quality of pharmaceutical care. I. One perspective of quality. AB - OBJECTIVE: To evaluate the concept of pharmaceutical care (PC) as a standard of quality care for ambulatory pharmacy practice. DATA SOURCES: Donabedian's article on the seven pillars or characteristics of quality provides a framework for a discussion of the merits of PC as a definition of quality. A MEDLINE search augmented by a manual review of International Pharmacy Abstracts was also used to identify pertinent English-language pharmacy literature; indexing terms included quality, community pharmacy services, ambulatory, pharmacy services, and pharmacist(s). STUDY SELECTION: Representative articles and studies promoting PC were considered. DATA EXTRACTION: The literature was independently reviewed by the primary author. DATA SYNTHESIS: An interpretation of the principles of Donabedian's article was applied to PC. PC appears to be consistent with the quality characteristics of efficacy and acceptability. The effectiveness, cost effectiveness, and efficiency of PC should be firmly established by its practitioners as barriers are eliminated and/or overcome. The pillars of optimality, equity, and legitimacy seem to be overlooked under the current definition of PC. This article contends that PC assumes an individualist definition of quality, by definition, because of its covenantal relationship with the patient. CONCLUSIONS: Quality is defined in terms of the values of individuals and society. For now, PC appears to be the appropriate standard for defining quality in pharmacy because of the importance of individual maximal benefits within our society. PMID- 8431626 TI - Hepatic drug metabolism in cystic fibrosis: recent developments and future directions. AB - OBJECTIVE: To review the most current information pertaining to hepatic drug metabolism in patients with cystic fibrosis (CF) and to explore the possible association between CF and specific pathways for the hepatic biotransformation of xenobiotics. DATA SOURCES: A MEDLINE search (key terms: cystic fibrosis, pharmacokinetics, metabolism, pharmacogenetics) was used to identify pertinent literature, including reviews. Research findings from the author's laboratory are also presented. STUDY SELECTION: Only recently reported (from 1988 to present), controlled, clinical investigations of hepatic drug metabolism in patients with CF are included. These investigations examined a mechanistic basis for altered drug biotransformation. Although uncontrolled clinical trials, case reports, and review articles are not included in the discussion, appropriate reference citations are made to these works. DATA EXTRACTION: Data from well-designed, controlled, clinical and basic investigations of altered hepatic drug biotransformation in patients with CF are summarized and discussed. New data from an ongoing study concerning the renal excretion of antipyrine metabolites in these patients are presented. DATA SYNTHESIS: In vivo studies of the formation clearance for metabolites of fleroxacin, sulfamethoxazole, and theophylline clearly demonstrate increased activity for important P-450 isoenzymes. These data are supported by an in vitro study that confirmed increased microsomal metabolism of theophylline to 1-methylxanthine, 3-methylxanthine, and 1,3-dimethyluric acid in a liver specimen from a patient with CF. These findings not only substantiate disease-specific increases in hepatic phase I biotransformation in patients with CF, but also verify the premise of substrate specificity for this pharmacogenetic phenomenon. Likewise, pharmacokinetic studies of drugs that undergo significant hepatic phase II biotransformation (e.g., furosemide, lorazepam, ibuprofen) appear to support increased hepatic drug clearance in patients with CF. This assertion has also been confirmed by a study of acetaminophen disposition, which demonstrated significantly increased formation clearance of the sulfate and glucuronide conjugates of the drug. Finally, the marked increase in the plasma clearance of indocyanine green, a pharmacologic probe for the biliary uptake and excretion of drugs, lends credence to the assertion that increased hepatic clearance of drugs in the presence of CF may be the consequence of disease specific changes in both enzyme activity and/or drug transport within the liver. CONCLUSIONS: Investigations of drug biotransformation in CF have revealed disease specific increases in the formation of drug metabolites. Future application of techniques in molecular biology and biochemical pharmacology will need to characterize the mechanistic basis for altered drug metabolism in CF and expand our knowledge of the relationship between drug metabolism phenotype and genotype; the impact of growth, development, and disease severity on drug metabolism; the potential role of CF gene products (i.e., CFTR) on intrahepatic drug transport and biotransformation; and the pharmacogenetic determinants of substrate specificity for hepatic drug metabolism in CF. PMID- 8431627 TI - Impact of pharmacist interventions on medication management by the elderly: a review of the literature. AB - OBJECTIVE: To review the impact of pharmacist interventions designed to assist older people in managing their medication regimens. DATA SOURCES: A computer search of literature published between 1975 and 1990 was conducted using MEDLINE. References were also identified from the bibliographies of pertinent articles. STUDY SELECTION: Studies included in the review were those evaluating pharmacist interventions that were designed to assist in medication management by people over 65 years of age. Only nine studies were identified by these criteria. Interventions that have not been evaluated are discussed briefly. The studies included were chosen by consensus of the authors. DATA EXTRACTION: A data extraction form was used to summarize the information in each study. RESULTS: This was a qualitative review. Some studies evaluating the effects of short verbal medication counseling episodes showed positive benefits; others showed no benefit. Written medication information, some memory devices, and audiovisual techniques have also been found to be of limited use. Self-medication programs for hospitalized elderly people need to be evaluated. CONCLUSIONS: This review identified the lack of published evaluations of pharmacist interventions in medication management by elderly people. Well-designed studies need to be performed to determine the effects of individualized advice and counseling. The cost-effectiveness of such interventions should be assessed, with consideration of long-term outcomes, such as readmission rates to the hospital and cost savings accruing from increased duration of independent living. PMID- 8431628 TI - Adverse reactions to human serum albumin. AB - OBJECTIVE: To describe the adverse effects associated with human serum albumin (HSA) administration. DATA SOURCES: A MEDLINE search and bibliography scanning were used to identify pertinent review articles, clinical studies, and case reports. STUDY SELECTION: Emphasis was placed on reporting the results of human studies with the primary objective of investigating adverse effects attributable to HSA administration. Clinical trials that reported the occurrence of adverse effects possibly associated with HSA were also reviewed. Animal data were included where pertinent. DATA EXTRACTION: Although isolated case reports were reviewed, data were primarily extracted from human studies involving large series of patients or studies that were randomized and prospective in nature. DATA SYNTHESIS: Alterations in coagulation, renal, cardiovascular, and pulmonary functions were identified as potential adverse effects following the administration of HSA. Occurrences of hypersensitivity reactions, trace metal loading, and serum amino acid alterations associated with these infusions were also noted and are described here. Pulmonary and cardiovascular systems appear to be particularly prone to complications from excessive HSA administration. Adverse effects such as HSA-induced hypersensitivity reactions may be severe, but occur infrequently. CONCLUSIONS: Controlled studies involving large numbers of patients are not currently available for an accurate assessment of the incidence of adverse effects attributable to HSA administration. Many of the reported reactions appear to be extensions of albumin's pharmacologic activities and would be expected to worsen following large doses of HSA. PMID- 8431629 TI - Using memory for pain in analgesic research. AB - OBJECTIVE: To determine the validity of pain intensity recall at 24 and 48 hours as a substitute for hourly pain assessments in repeated-dose analgesic studies. SETTING: Orthopedic unit of an acute care teaching hospital. PARTICIPANTS: Eighty four patients undergoing arthroscopic reconstruction of the anterior cruciate ligament, using the patellar tendon, who were participating in a randomized, double-blind, parallel-group analgesic study. INTERVENTIONS: Patients rated their pain intensity every hour (while awake) for 48 hours and their recall of worst, least, and usual pain intensity at 24 and 48 hours using a visual analog scale (VAS). MAIN OUTCOME MEASURES: This study examined the relationship between recall of worst, least, and usual pain intensity at 24 and 48 hours and the experienced maximum, minimum, and mean pain intensity VAS scores obtained from hourly assessments over the 0-24- and 0-48-hour periods, respectively. The significance of differences between recalled and experienced pain intensity variables was assessed. RESULTS: Worst, least, and usual pain recall at 24 and 48 hours were highly correlated with experienced maximum, minimum, and mean pain from hourly reports, respectively, over the 0-24- and 0-48-hour periods (Pearson correlation coefficients, r = 0.80-0.89, p < 0.0001). Among the three pain recall variables, usual pain showed the highest correlation with hourly measurements. There were no significant differences between recalled pain and the corresponding measures of pain from the hourly VAS scores, except in the case of 48-hour recall of worst pain (Student's t-test, p = 0.001). CONCLUSIONS: The close agreement between actual pain experience and recall of pain provides support for the use of pain recall in assessing analgesic efficacy in clinical trials. PMID- 8431630 TI - Retreat or charge on SI units? PMID- 8431631 TI - SI units--are we leaders or followers? PMID- 8431632 TI - SI units: is it pass the mass but hold the mole. PMID- 8431633 TI - Subregional physical mapping of an alpha B-crystallin sequence and of a new expressed sequence D11S877E to human 11q. AB - We report the regional assignment on Chromosome (Chr) 11q of two cDNA clones selected as sequences expressed in mature kidney and not expressed in Wilms' tumor. Clone T70 was identified as an alpha B-crystallin sequence (CRYA2). CRYA2 has previously been mapped to 11q22.3-23.1 by in situ hybridization. Clone 6.2 represents a new gene expressed in adult and fetal kidney, pancreas, and liver. In order to map sequences corresponding to clone 6.2 and to physically define the boundaries of the localization of CRYA2, we used somatic cell hybrids carrying either different human chromosomes or Chr 11 segments and a cell line established from a patient with an interstitial deletion of region 11q14.3-q22.1. We showed that CRYA2 lies proximal to the 11q23.2 breakpoint defined by the constitutional t(11;22) and distal to the 11q22.1 breakpoint (between D11S388 and D11S35) of a constitutional interstitial deletion. This is in agreement with previous data obtained by in situ hybridization and provides proximal and distal physical benchmarks for this localization. Clone 6.2-related sequence (D11S877E) was assigned to region 11q23.2-q24.2 defined by the breakpoints of the constitutional t(11;22) and of the Ewing's sarcoma neuroepithelioma t(11;22). PMID- 8431634 TI - The identification of Y chromosome-linked markers with random sequence oligonucleotide primers. AB - The polymerase chain reaction (PCR)-based technique of random amplification of polymorphic DNA (RAPD) is extremely useful for developing DNA-based markers. We previously identified a linkage group of eight unmapped RAPD markers that distinguish C57BL/6J and DBA/2J mice (Mammalian Genome 3: Woodward et al., 73-78, 1992). In this study, we report that all eight markers are Y Chromosome (Chr) linked. One additional Y-linked RAPD was discovered serendipitously during the screening of a C3H/HeJ x (C3H/HeJ x SJL/J)F1 BC1 population. The segregation of all nine markers was analyzed with a panel of 14 independent inbred strains of male mice. The nine markers could be divided into three distinct groups: (1) DYByu2, DYByu5, DYByu6, and DYByu8 identify both the M.m. musculus and M.m. domesticus type Y Chr; (2) DYByu1, DYByu3, DYByu4, and DYByu7 are specific for the M.m. musculus type; and (3) DYByu9 is specific for the M.m. domesticus type. The results clearly indicate that the RAPD technique can be used to identify Y Chr-linked, DNA-based markers in mammalian species. PMID- 8431635 TI - Order of bovine DRB3, DYA, and PRL determined by sperm typing. AB - The order and recombination fractions (theta) between the bovine major histocompatibility complex DRB3, DYA, and prolactin (PRL) genes were determined by typing of 254 sperm from a triply heterozygous bull. A recently developed method, primer extension preamplification (PEP), was used to amplify the bovine sperm genome prior to amplification of specific loci by the polymerase chain reaction (PCR). At least 28 copies of the DRB3, PRL, or DYA gene were obtained from 50 cycles of PEP. For sperm typing, alleles of each locus were discriminated by restriction endonuclease cleavage of PCR products and polyacrylamide gel electrophoresis of the restriction fragments. The most likely gene order is PRL DRB3-DYA, with theta = 0.025 (+/- 0.012) and theta = 0.150 (+/- 0.024), respectively. The odds are 128:1 in favor of this order in comparison with the second most likely order DRB3-PRL-DYA. Our results demonstrate the power of sperm typing in concert with PEP for multilocus gene mapping. PMID- 8431637 TI - Chromosomal localization of human homologs of the Drosophila heterochromatin protein 1 (HP1) gene. PMID- 8431636 TI - Partial inversion of gene order within a homologous segment on the X chromosome. AB - The locus for the erthyroid transcription factor, GATA1, has been positioned in the small interval between DXS255 and TIMP on the proximal short arm of the human X Chromosome (Chr) by use of a partial human cDNA clone and a well-characterized somatic cell hybrid panel. Analysis of selected recombinants from 108 Mus musculus x Mus spretus backcross progeny with the same clone confirmed that the homologous murine locus (Gf-1) lies between Otc and the centromere of the mouse X Chr. These data imply that a partial inversion of gene order has occurred within the conserved segment that represents Xp21.1-Xp11.23 in human (CYBB-GATA1) and the proximal 6 cM of the mouse X Chr (Gf-1-Timp). Furthermore, they indicate that the mouse mutant scurfy and the human genetic disorder Wiskott-Aldrich syndrome, which have been mapped to the same regions as GATA1/Gf-1 in both species, may indeed be homologous disorders. PMID- 8431638 TI - The B-HLH protein encoding the M-twist gene is located by in situ hybridization on murine chromosome 12. PMID- 8431639 TI - Sulfated glycoprotein-2 (Sgp-2) maps to mouse chromosome 14. PMID- 8431640 TI - Genomic mapping of intracisternal A-particle proviral elements. AB - Intracisternal A-particle (IAP) proviral elements are moderately reiterated and widely dispersed in the mouse genome. Oligonucleotide probes have been derived from three distinctive IAP element subfamilies (LS elements) that are transcriptionally active in normal mouse B- and T-cells. In HindIII digests, LS element-specific oligonucleotides each react with a limited number of restriction fragments that represent junctions between proviral and flanking DNA. These fragments have characteristic strain distribution patterns (SDPs) which are polymorphic in the DNAs of different mouse strains. We have established chromosomal assignments for 44 LS proviral loci by comparing their SDPs with those of known genetic markers in the BXD set of RI mouse strains. Some of the loci have also been scored in the CXB RI set. The IAP LS loci can provide a significant number of markers with a recognized genetic organization to the mouse genome map. PMID- 8431641 TI - Mapping of the human homologs of the murine paired-box-containing genes. AB - Mutations in paired-box-containing (Pax) genes have recently been found to be the primary lesions underlying human genetic disorders such as Waardenburg's Syndrome type 1 and mouse developmental mutants such as undulated (un), splotch (Sp), and small eye (Sey). In addition, PAX-6 is a strong candidate gene for aniridia in man. Eight independent Pax genes have been isolated in the mouse. All eight map to distinct regions of the mouse genome; they do not appear to be clustered in the same way as some groups of homeobox-containing genes. We have now mapped the human homologs of all eight of these genes; PAX genes are found on human Chromosomes (Chr) 1, 2, 7, 9, 10, 11, and 20. PMID- 8431642 TI - Map of seven polymorphic markers on rat chromosome 14: linkage conservation with human chromosome 4. AB - Seven polymorphic markers identified by polymerase chain reaction (PCR) amplification, including markers for six genes--DRD1L (dopamine receptor, D1-like 2), GLUKA (glucokinase), PF4 (platelet factor 4), ALB (albumin), AFP (alpha fetoprotein), and BSP (bone sialoprotein)--and one anonymous locus (D14N52), were mapped to a single 67-cM linkage group with F2 intercross progeny of F344/N and LEW/N inbred rat strains. Two of these markers, ALB and AFP, have previously been assigned to rat Chromosome (Chr) 14, allowing assignment of this entire linkage group. Five of the markers--DRD1L, PF4, ALB, AFP, and BSP--have been physically mapped to a large region of human Chr 4 encompassing the p arm and the q arm to band q28. Homologs of two of the markers, ALB and AFP, have been mapped to Chr 5 in the mouse. Comparison of human Chr 4 with the homologous regions on Chr 14 of the rat and Chr 5 of the mouse indicated that linkage conservation with human Chr 4 extends over a greater region in the rat than in the mouse. The markers described here were found to be highly polymorphic in twelve inbred strains (F344/N, LEW/N, ACI/N, BUF/N, BN/SsN, LOU/MN, MNR/N, MR/N, SHR/N, WBB1/N, WBB2/N, and WKY/N). These polymorphic markers should be useful in genetic linkage studies of important phenotypes in rats. PMID- 8431644 TI - Reduction of structured population models to threshold-type delay equations and functional differential equations: a case study. AB - It is shown by way of a simple example that certain structured population models lead naturally to differential delay equations of the threshold type and that these equations can be transformed in a natural way to functional differential equations. The model examined can be viewed as a model of competition between adults and juveniles of a single population. The results indicate the possibility that this competition leads to instability. PMID- 8431643 TI - The alpha 2(XI) collagen gene lies within 8 kb of Pb in the proximal portion of the murine major histocompatibility complex. AB - A number of serious hereditary disorders are now known to be associated with defective expression of collagen genes, and these findings have underscored the important and varied roles that the collagen family of genes must play during normal mammalian development. Although the activities of genes encoding the quantitatively major types of collagen are fairly well characterized, functions of the many minor types of collagen remain a matter of speculation. As a first step toward a functional analysis of type XI collagen, a member of this class of poorly understand "minor" collagen proteins which is expressed primarily in hyaline cartilage, we have used human probes for the gene encoding the protein's alpha 2-subunit (COL11A2) to isolate and map homologous murine DNA sequences. Our results demonstrate that Col11a-2 is embedded within the major histocompatibility complex (MHC), within 8.4 kb of the class II pseudogene locus, Pb, and confirm that human and murine alpha 2(XI) collagen genes are located in very similar genomic environments. The conserved location of these genes raises the possibility that type XI collagen genes may contribute to one or more of the diverse hereditary disorders known to be linked to the MHC in mouse and human. PMID- 8431645 TI - A stochastic model of the HIV epidemic and the HIV infection distribution in a homosexual population. AB - In this paper we develop a stochastic model for the HIV epidemic in a homosexual population and use the model to characterize the HIV infection distribution and seroconversion distribution. Through computer-generated infection distributions and seroconversion distributions, we assess the effects of various risk factors on these distributions. The fitting of some data sets generated by computer suggests that the three-parameter generalized log-logistic distribution should be assumed as the infection distribution for the proposed stochastic model of HIV epidemics. PMID- 8431646 TI - The probability of permanence. AB - Numerical experiments suggest that cooperation is a very rare phenomenon in autocatalytic networks with more than about five interacting species. There is strong evidence that the probability for cooperative behavior in random networks decreases at least exponentially and at most as an2 with the number n of interacting species. The evolution of larger persistent networks by subsequent incorporation of additional species into a cooperative network is shown to be even less probable. This leads to the conclusion that hypercycle-type interactions alone are not sufficient to maintain the genetic information of more than a few interacting species in a pure RNA world. PMID- 8431647 TI - A stochastic model of radiation carcinogenesis: latent time distributions and their properties. AB - A stochastic model of radiation carcinogenesis is proposed that has much in common with the ideas suggested by M. Pike as early as 1966. The model allows us to obtain a parametric family of substochastic-type distributions for the time of tumor latency that provides a description of the rate of tumor development and the number of affected individuals. With this model it is possible to interpret data on tumor incidence in terms of promotion and progression processes. The basic model is developed for a prolonged irradiation at a constant dose rate and includes short-term irradiation as a special case. A limiting form of the latent time distribution for short-term irradiation at high doses is obtained. This distribution arises in the extreme value theory within the random minima framework. An estimate for the rate of convergence to a limiting distribution is given. Based on the proposed latent time distributions, long-term predictions of carcinogenic risk do not call for information about irradiation dose. As shown by computer simulation studies and real data analysis, the parametric estimation of carcinogenic risk appears to be robust to the loss of statistical information caused by the right-hand censoring of time-to-tumor observations. It seems likely that this property, although revealed by means of a purely empirical procedure, may be useful in selecting a model for the practical purpose of risk prediction. PMID- 8431648 TI - A qualitative analysis of some models of tissue growth. AB - Using maximum principles for parabolic and elliptic operators, we examine, in a general way, some models of tissue growth. These typically consist of a model mechanism for the diffusion of a mitotic inhibitor (growth inhibitory factor, GIF) throughout the tissue. Central to the modeling is the inclusion of a source function that models the production of GIF throughout the tissue. We examine the effect this term has on the resulting distribution of GIF in the tissue and comment on the appropriateness of different source functions, in particular a uniform production rate or a nonuniform production rate of inhibitor. Given that it is more appropriate to infer from the patterns of mitosis that are observed experimentally in various tissues the GIF concentration profile rather than the source function profile, it may be more appropriate to use these types of models to determine the qualitative form of the source term rather than proposing this function a priori. PMID- 8431649 TI - Chaos in a periodically forced predator-prey ecosystem model. AB - We subject to periodic forcing the classical Volterra predator-prey ecosystem model, which in its unforced state has a globally stable focus as its equilibrium. The periodic forcing is effected by assuming a periodic variation in the intrinsic growth rate of the prey. In nondimensional form the forced system contains four control parameters, including the forcing amplitude and forcing frequency. Numerical experiments carried out over sections of the parameter space reveal an abundance of steady-state chaotic solutions. We graph Poincare maps and calculate Lyapunov exponents and fractal dimensions for a representative selection of strange attractors. The transitions to chaos were found to be either via a Feigenbaum cascade of period-doubling bifurcations or via frequency locking. PMID- 8431650 TI - Spreading of excitation in 3-D models of the anisotropic cardiac tissue. I. Validation of the eikonal model. AB - In this work we investigate, by means of numerical simulations, the performance of two mathematical models describing the spread of excitation in a three dimensional block representing anisotropic cardiac tissue. The first model is characterized by a reaction-diffusion system in the transmembrane and extracellular potentials v and u. The second model is derived from the first by means of a perturbation technique. It is characterized by an eikonal equation, nonlinear and elliptic in the activation time psi(x). The level surfaces psi(x) = t represent the wave-front positions. The numerical procedures based on the two models were applied to test functions and to excitation processes elicited by local stimulations in a relatively small block. The results are in excellent agreement, and for the same problem the computation time required by the eikonal equation is a small fraction of that needed for the reaction-diffusion system. Thus we have strong evidence that the eikonal equation provides a reliable and numerically efficient model of the excitation process. Moreover, numerical simulations have been performed to validate an approximate model for the extracellular potential based on knowledge of the excitation sequence. The features of the extracellular potential distribution affected by the anisotropic conductivity of the medium were investigated. PMID- 8431651 TI - Extending the multiple indicator dilution method to include slow intracellular diffusion. AB - The traditional multiple indicator dilution (MID) method is extended to incorporate cytoplasmic concentration gradients due to slow intracellular diffusion of the permeable molecule. The new model is governed by a system of partial differential equations that are solved using Laplace transformation. An analysis of the transformed solution shows that the traditional MID method is a special case of the extended model. We then use simulation analysis to show that the traditional MID model and the new diffusion model generate similar outflow curves. However, when the traditional MID equations were used to analyze outflow curves generated using a system in which intracellular diffusion is slow compared to other transport processes, the recovered rate constants for the transmembrane and excretion processes were incorrect. The diffusion model permits estimation of the rate of intracellular transport of amphipathic molecules from suitable indicator dilution data. PMID- 8431652 TI - Global behavior of n-dimensional Lotka-Volterra systems. AB - The behavior of Lotka-Volterra systems is studied using as tools the results from positivity and auxiliary functions that decrease along the trajectories. One typical result is that if a decomposition of the interaction matrix into a product of a symmetric and an off-diagonal nonnegative matrix is possible, then all the trajectories either go to equilibria or cannot remain in any compact set of the interior of the positive orthant. PMID- 8431653 TI - On nonaxisymmetric entry flow at very low Reynolds numbers. AB - The eigensolution of nonaxisymmetric entry flow of a Newtonian viscous fluid with very small Reynolds number in a semiinfinite rigid circular pipe is obtained. Leading eigenvalues are computed for steady flow and two periodic cases. The result shows that the entry length for nonaxisymmetric flows should be longer than the entry length for axisymmetric flows. PMID- 8431654 TI - The selection of plastic materials for blood bags. AB - The procedures used in the preparation of blood components together with the processes used in the manufacture of multiple blood bag systems impose a unique combination of requirements that severely limits the selection of plastics. Plasticized PVC, the plastic used in the first blood bags introduced by Carl Walter over 40 years ago, remains the material of choice today. Blood bag material research has focused on two areas: (1) the development of containers with increased gas permeability for the storage of platelet concentrates; and (2) the reduction or elimination of plasticizer contamination of stored blood components. This research has led to the development of several second-generation containers that have improved the quality and extended the allowable storage period of platelet transfusion products. Plastics virtually free of extractives are available for the storage of platelets and plasma, but elimination of plasticizers from RBC products has not yet been achieved. PMID- 8431655 TI - Bone marrow donor registries and international cooperation. PMID- 8431656 TI - Prestorage leukocyte depletion of blood products in a closed system. PMID- 8431657 TI - HLA homozygosity and the risk of related-donor transfusion-associated graft versus-host disease. AB - Based on the prevailing interpretation of recent data implicating donor homozygosity for an HLA haplotype shared with a heterozygous recipient, it is our conclusion that the risk of TA-GVHD for a sibling of the blood donor is about half that of a parent or a child, and the risk for a grandparent, a grandchild, or a blood-related aunt, uncle, niece, or nephew is about the same as the risk for the donor's sibling. Consequently, the current recommendation and the practice of irradiating cellular blood products for transfusion to first-degree relatives but not for transfusion to more distant relatives is insufficient. We believe that the recommendation for prophylactic irradiation of cellular blood products, based on the current understanding of its apparent safety, should be extended at least to include transfusion to the donor's grandparents, grandchildren, and blood-related aunts, uncles, nieces, and nephews. PMID- 8431658 TI - Inactivation of viruses in blood and plasma products. PMID- 8431660 TI - Role of natural killer cells in controlling local tumor formation and metastatic manifestation of different 3LL Lewis lung carcinoma cell clones. AB - Using two cell clones derived from 3LL Lewis carcinoma; an NK-resistant (designated A6) and an NK-susceptible (designated F2) clone, we investigated the effect of the NK system on local tumor growth and metastasis. Both clones generated local tumors at the inoculation site somewhat faster in NK-deficient (bg/bg) than in normal mice. In addition, these tumors grew slightly faster in the bg/bg mice. However, the effect of the NK system on the metastatic spread of these clones was much more prominent. The F2 cells were profoundly less metastatic than the A6 cells when inoculated into normal mice, whereas in the NK deficient mice, both clones were highly metastatic. Thus, the NK system appears to be effective primarily in controlling the metastatic spread of the 3LL cells and has a lesser effect on their local tumor formation. PMID- 8431659 TI - Generation of natural killer cells from long-term cultures of mouse bone marrow. AB - The features of a mouse long-term bone marrow culture (LTBMC) system that produces natural killer (NK) cell activity are described. Over a 4-week period in the NK-LTBMC, cellularity dropped from approximately 2.5 x 10(7) to 8 x 10(5) cells/25-cm2 flask. About 3 x 10(5) of these cells were loosely adherent. The cultures at this time contained about one-third the spleen colony forming units, one-tenth the granulocyte macrophage colony forming units and about one-third the transplantable NK progenitor activity of fresh bone marrow (BM), and no detectable NK cell activity. In the 4-week NK-LTBMC, IL-2-responsive precursor cells appeared to be selectively maintained and gave an 8-fold higher activity after culture with human recombinant IL-2 (rIL-2) than did fresh BM. The addition of 50-5,000 IU/ml of rIL-2 resulted, after a minimal 3-day lag, in progressively increased cellularity for as long as 13 days. The percentage and staining intensity of NK-1.1+ cells increased with time after addition of rIL-2. CD3 epsilon + cells were occasionally seen and B220+ cells were present in low numbers at day 7 and slowly increased through day 13. The stroma was necessary for IL-2-dependent development of NK activity. PMID- 8431661 TI - Secretion of two different flowing masses by lymphokine-activated killer cells. AB - When grown on mesenchyme-fibroblastoid monolayers made of 16-day-old embryos, lymphokine-activated killer (LAK) cells in clones derived from nude mouse lymph node cells are signaled to synthesize and secrete two mucoid masses. The first is made of chondroitin sulfate, as determined by the degradation of 35S- and [3H]glucosamine-labeled macromolecules in the extracellular matrix, by hyaluronidase, and by chondroitin sulfate lyase AC. This determination correlates with the distinctive blue staining by periodic acid-Schiff/alcian blue (PAS-Ab) at pH 1.0. In the present study, two different masses were identified when methanol-fixed and dried LAK cells and their secretions were examined prior to staining. The chondroitin-sulfate-containing mass appeared as an optically bright structure. It also produced a positive fluorescence with rabbit anti-mouse perforin. The second structure, which appeared as a flowing material or as filling holes in the first, could be identified by its high optical density. However, it was not stained by PAS-Ab and was not blackened by osmium tetroxide. The biochemical nature of the second mass has yet to be determined. Both masses seemed eventually to mix, producing pools, in lacunae, or to spread into the culture space. PMID- 8431662 TI - Kinetics of cortisol, interleukin-2 and interleukin-3-like activity levels following surgical intervention. AB - Cortisol, interleukin(IL)-2 and IL-3-like activity (IL-3-LA) levels were examined in two groups of patients before and after surgery. One group consisting of 11 patients underwent cholecystectomy; the other comprising 17 patients with malignant diseases of the gastrointestinal tract underwent a removal of the tumor. In both groups there were similar fluctuations in cortisol levels after surgery, i.e. a statistically significant increase at day 2 after operation with a decrease to normal values at day 14. The levels of IL-2 and IL-3-LA production in the two groups followed a different pattern. In patients with cholecystectomy the IL-2 and IL-3-LA levels showed a marked decrease at day 2 with a gradual increase on the following days. In cancer patients IL-2 was at its lowest level before surgery and started to increase gradually till day 14 after surgery. The lowest level of IL-3-LA was at day 2 after surgery and it increased gradually from day 7 to 14. It is suggested that the fluctuations of these two cytokines after surgery are related to the levels of corticosteroids which have been shown to inhibit the production of IL-2 and IL-3-LA in vitro. The observed increase of cortisol level with a concomitant decrease of IL-2 and IL-3-LA after surgery may further explain the immunosuppression observed after operation. PMID- 8431664 TI - Mannitol: potential for rebound intracranial hypertension? PMID- 8431663 TI - Comparison of immune parameters in patients with one or two primary malignant neoplasms. AB - The purpose of this study was to correlate cellular immune responses and cytokine production in vitro between patients with one or two primary malignant neoplasms. One hundred and ninety-three patients (110 patients with one primary malignant neoplasm (group I), and 83 patients with two primary tumors (group II), entered this study. Mononuclear cells isolated from peripheral blood were tested in the following tests: (a) proliferative responses in the autologous and allogeneic mixed lymphocyte reaction (auto- and allo-MLR respectively): (b) natural killer cell activity; (c) production of interleukin-2 during the allo-MLR, and (d) interleukin-1 beta production by lipopolysaccharide-stimulated monocytes. All these parameters were found to be decreased in cancer patients as compared to normal donors (p < 10(-3)). In addition, we were able to detect significant differences between the values obtained from patients in groups I and II (p < 10( 2)). These data suggest a further impairment in cancer patients' immune status after the diagnosis of a second malignancy. PMID- 8431665 TI - Enalapril premedication attenuates the blood pressure response to tracheal intubation and stabilizes postoperative blood pressure after controlled hypotension with sodium nitroprusside in neurovascular patients. AB - Oral premedication with enalapril, 0.1 mg/kg was compared with placebo in 22 patients subjected to craniotomy and ligation of an intracranial aneurysm or extirpation of an arteriovenous malformation. Balanced hypotensive anesthesia was used with sodium nitroprusside (SNP) as the main hypotensive agent. The hypertensive response to laryngoscopy and tracheal intubation was significantly attenuated by enalapril (p = 0.020). The mean blood pressure was lower and more stable in the intensive care unit after enalapril than after placebo (p = 0.044). The median SNP dose rate tended to be lower in the enalapril-pretreated patients [0.6 (range of 0-3.5) micrograms/kg/min] compared to the placebo group [1.4 (0.4 5.8) micrograms/kg/min] (p = 0.12). Concentrations of plasma catecholamines, vasopressin, and endothelin as well as serum osmolality, arterial blood gases, and plasma electrolytes and level of consciousness were repeatedly measured. Enalapril had no significant effects on these variables. Plasma renin activity was increased and serum angiotensin converting enzyme (ACE) activity was reduced in the expected manner by enalapril. We found premedication with an ACE inhibitor favorable for hypotensive anesthesia in neurovascular patients as assessed by the circulatory responses. PMID- 8431666 TI - The past, present, and future of research in neuroanesthesia. PMID- 8431667 TI - Alfentanil administered prior to endotracheal suctioning reduces cerebral perfusion pressure. AB - The effects of i.v. alfentanil on the intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were prospectively evaluated during endotracheal suctioning of head-injured adults. Seven subjects underwent trials of saline and alfentanil at 15 and 30 micrograms/kg prior to a stereotypic stimulus of endotracheal suctioning. Investigators and medical personnel were blinded with respect to the intravenous substance administered. The ICP, mean arterial pressure (MAP), heart rate (HR), peak and plateau inspiratory pressures, and Glasgow Coma Scores were recorded. By analysis of variance with repeated measures, data demonstrated that the alfentanil trials were associated with a decline in the CPP relative to control. The CPP was significantly reduced (p < 0.05) in the alfentanil dosage trials 5 min after i.v. alfentanil injection. There was no evidence of alteration of chest wall compliance to explain apparent elevations in the ICP or reductions in the MAP. These findings suggest caution in the use of alfentanil in the neurotrauma patient. Potential mechanisms of reduction in cerebral perfusion will require further evaluation. Formal assessment of other synthetic opiates with respect to efficacy and safety in the neurotrauma patient is advised. PMID- 8431668 TI - Pharmacokinetics and effects of mannitol on hemodynamics, blood and cerebrospinal fluid electrolytes, and osmolality during intracranial surgery. AB - Fifteen patients who underwent surgery for intracranial tumors under general anesthesia were given mannitol (1 g/kg of body weight) over 30 min. Measurements of mannitol concentration, osmolality, and electrolytes were determined in blood and cerebrospinal fluid (CSF) samples collected over an 8-h period. Seven sets of hemodynamic observations and four sets of intracranial pressure (ICP) measurements were also made. Mannitol disappeared from plasma in a biexponential manner. The mean maximal plasma concentration was 5.91 mg/ml at the end of mannitol infusion and decreased to 0.58 mg/ml after 8 h. The plasma half-life for the distribution phase was 0.16 h and for the elimination phase was 2.44 h. The distribution volume was 17.0 L and total plasma clearance 87.4 ml/min. There were marked interindividual variations of mannitol concentration in the CSF. The mean CSF concentration at 8 h was 97.1 micrograms/ml, started to decline earlier in 10 of 12 patients, and never exceeded 12% of that in plasma. Osmolality in serum increased with a maximum at the end of mannitol infusion (from 292 +/- 7 mOsmol/kg to 310 +/- 14 mOsmol/kg; p < 0.01), whereas CSF osmolality was unchanged, thus giving rise to a positive blood-CSF osmotic gradient of at least 10 mOsmol/kg for about 30 min. At the end of the mannitol infusion, cardiac output and pulmonary capillary wedge pressure increased significantly, whereas the hematocrit decreased. ICP was observed in five patients for 45 min, and mannitol induced a mean reduction from 11 +/- 4 to 4 +/- 2 mm Hg (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431669 TI - Brain eicosanoid levels during temporary focal cerebral ischemia in rats: a microdialysis study. AB - After transient cerebral ischemia, the brain is vulnerable to additional injury via hypoperfusion deficits. Eicosanoids with vasoconstrictor properties, such as thromboxane A2 (TxA2), may worsen postischemic hypoperfusion. The effect of temporary middle cerebral artery occlusion (MCAo) on brain TxB2 (the stable metabolite of TxA2) was evaluated in isoflurane-anesthetized rats. Microdialysis probes were placed in the caudate nucleus and temporal cortex. Each rat underwent one of the following ischemic regimens: groups I, II, and III--MCAo was maintained for 60, 120, and 180 min, respectively, followed by 120 min of reperfusion; group IV--a sham group in which MCAo and reperfusion were simulated; group V--7 h of MCAo only. Dialysate was measured for TxB2 by radioimmunoassay. Brain levels of TxB2 did not deviate from baseline during MCAo (or in the sham group). In contrast, during reperfusion, there was a significant increase in TxB2 following 180 min of MCAo but not after 60 or 120 min or MCAo (p < 0.05). These data indicate that, in this model of cerebral ischemia, TxB2 does not increase during MCAo. However, following a threshold duration of MCAo (180 min), the vasoconstrictor TxB2 may modulate postischemic hypoperfusion. These findings may have implications in the pharmacologic treatment of postischemic hypoperfusion and reperfusion brain injury. PMID- 8431670 TI - Repair of two unruptured intracranial aneurysms in the presence of coarctation of the aorta-anesthetic implications and management. AB - A case of two incidental familial intracranial aneurysms associated with asymptomatic coarctation of the aorta is reported. Priority was assigned to aneurysm surgery, which was accomplished by means of two distinct procedures, both requiring moderate, deliberate hypotension. Invasive monitoring always included radial and femoral as well as pulmonary artery pressures, together with mixed venous oximetry and thermodilution cardiac outputs. Spinal somatosensory evoked potentials were also continuously registered, to prevent spinal cord ischemia. In fact, even moderate hypotension may critically reduce perfusion in the lower, already hypotensive district, because of coarctation. PMID- 8431671 TI - Cerebral injury: are manipulations of carbon dioxide beneficial? PMID- 8431672 TI - Hyperventilation as a therapeutic intervention: do the potential benefits outweigh the known risks? PMID- 8431673 TI - Lead and the terminal mitochondrial enzymes of haem biosynthesis. AB - Lead exposure causes increases in urinary coproporphyrin excretion and the accumulation of zinc protoporphyrin in red cells. In the conventional view of the effect of lead on haem biosynthesis, the accumulation of these metabolites results from lead inhibition of two of the mitochondrial enzymes of haem biosynthesis, coproporphyrinogen oxidase (EC 1.3.3.3) and ferrochelatase (EC 4.99.1.1). This review critically assesses the evidence for the inhibition of these enzymes. We consider this evidence to be inconclusive and alternative explanations for the increased concentrations of coproporphyrin and zinc protoporphyrin are proposed. PMID- 8431674 TI - Simple determination of hydrochlorothiazide in human plasma and urine by high performance liquid chromatography. AB - The diuretic drug hydrochlorothiazide (HCT) is used mainly for treatment of mild to moderate hypertension and is usually administered with other drugs. An assay for the determination of HCT in human plasma and urine by high performance liquid chromatography (HPLC) has been developed. Samples were purified by solvent extraction and analysed by reversed phase HPLC with ultraviolet detection, using hydroflumethiazide as the internal standard; plasma was eluted using gradient elution and urine was analysed isocratically. The method is simple to perform, is sensitive (detection limit 0.01 micrograms/mL in plasma and 0.2 micrograms/mL for urine); it showed good reproducibility (3-8%). A great number of drugs did not interfere with the assay and the method was used for pharmacokinetic studies in healthy subjects, but samples from patients can also be analysed with high selectivity. PMID- 8431675 TI - Biodegradation of a carbamate pesticide, Propoxur, in rat tissues. AB - Propoxur (Baygon, 2-isopropoxyphenyl N-methylcarbamate) is a carbamate pesticide commonly used against house insects. When the insecticide was administered intramuscularly in rats it was converted to a new metabolite which was found to be present in the serum, liver, kidney and brain 6 h after the administration of the pesticide. The metabolite was purified by high performance liquid to chromatography and comparison of the infrared spectra of Propoxur and the metabolite showed that a deamination reaction was responsible for the formation of the metabolite from the parent pesticide. The pesticide also induced haematological changes such as an increased level of total bilubrin, amylase and glutamic-oxalacetic transaminase and decrease of cholinesterase activity, indicating damage of the liver and nervous system in rats. PMID- 8431676 TI - Measurement of terbutaline and salbutamol in plasma by high performance liquid chromatography with fluorescence detection. AB - A method is described for the determination of terbutaline and salbutamol in plasma from patients given maximal therapy for brittle asthma. The analytes were isolated by solid phase extraction on alkali-treated Bond-Elut, unmodified, silica columns and measured by high performance liquid chromatography with fluorescence detection (excitation wavelength 200 nm). The limits of detection for a 1 mL sample containing salbutamol and terbutaline were 1 microgram/L and 2.5 micrograms/L, respectively. The intra-assay precision (CV) for samples containing 25 micrograms/L was 3.6 and 5.0% respectively. This method was applied to the measurement of terbutaline in samples from patients given continuous infusions of the drug to assess whether this treatment might result in toxicity. PMID- 8431677 TI - Simultaneous determination of salbutamol and terbutaline at overdose levels in human plasma by high performance liquid chromatography with electrochemical detection. AB - A multidimensional column chromatographic method involving electrochemical detection using a carbon fibre microelectrode flow cell was optimized and successfully applied to the simultaneous determination of salbutamol and terbutaline in plasma at overdose levels. This method performs, in a single step, an efficient extraction and clean-up of salbutamol and terbutaline from human plasma. The calibration graphs over three days were linear over the calibration range 20-100 ng/mL plasma with a limit of detection of 1 ng and 0.8 ng/mL plasma for salbutamol and terbutaline, respectively. The intra- and inter-assay coefficients of variation were less than 8% and the recoveries ranged from 94 to 96%. The accuracy of the assay, which was defined as the percentage difference between the mean concentration found and the theoretical concentration, was 7% or better. The proposed method combines the advantages of being simple, reproducible and selective in the presence of other sympathomimetic and commonly ingested drugs and is suitable for routine analyses to obtain valuable information about the clinical effects and treatment of overdose with these drugs. The whole procedure takes ca. 10 min and compares favourably with detection at a conventional glassy carbon electrode. PMID- 8431678 TI - Analysis of morphine and its 3- and 6-glucuronides by high performance liquid chromatography with fluorimetric detection following solid phase extraction from neonatal plasma. AB - A rapid, sensitive and simple to operate high performance liquid chromatographic method for the simultaneous determination of morphine, morphine-3-glucuronide and morphine-6-glucuronide in plasma is described. The drug and its metabolites were extracted from plasma using commercially available reversed phase octylsilane bonded silica columns (1 mL Bond Elut C8, 50 mg). Chromatographic separation of morphine and its metabolites was achieved using a mobile phase, consisting of 2 mM sodium dodecyl sulphate in 0.05% phosphoric acid:acetonitrile (71.5:28.5 by volume), at a flow-rate of 1.2 mL/min, in conjunction with a Waters Nova-Pak C18 column (300 x 3.9 mm). The analytical column was used in combination with a Guard Pak module containing a Nova-Pak C18 Guard-Pak insert. Using fluorescence detection (excitation 245 nm, emission 335 nm), plasma levels in the region of 5 10 micrograms/L for the drug and its metabolites can be detected with only 200 microL of plasma. The method has been applied to studies of the disposition of morphine and its metabolites in premature neonates requiring mechanical ventilation who were receiving the drug intravenously; preliminary findings in patients at steady state are presented. PMID- 8431679 TI - Determination of 1,5-anhydroglucitol in urine by high performance liquid chromatography and an enzyme sensor. AB - A simple high performance liquid chromatographic method combined with an enzyme sensor has been developed to measure 1,5-anhydroglucitol in urine. The enzyme sensor consists of a hydrogen peroxide electrode and a chitosan membrane of an immobilized pyranose oxidase. As the system does not resist interfering substances, urine samples are first purified by passing them through a two-layer column packed with (1) strongly basic anion (OH- form, the upper layer) and (2) strongly acidic cation (H+ form, the lower layer) exchange resins. 1,5 Anhydroglucitol is efficiently recovered in the flow-through fraction of the column. In this system, the minimum detectable concentration of 1,5 anhydroglucitol is 0.1 mg/L, and the measurable range extends from 0.1 to 60 mg/L. The coefficient of variation values of the within-day and day-to-day precisions are 3.0-6.5% and and 4.4-6.7% respectively, and there is good agreement between the results measured by our method and those obtained by the gas-liquid chromatographic/mass spectrometric method (r = 0.994). The method we have described here has been successfully used to elucidate a mechanism for the reducing 1,5-anhydroglucitol level in the serum and plasma of patients. PMID- 8431680 TI - Determination of 5,10,15,20-tetra-(m-hydroxyphenyl)chlorin in human plasma by high performance liquid chromatography. AB - A high performance liquid chromatographic method for the determination of the photodynamic chemotherapeutic agent 5,10,15,20-tetra(m-hydroxyphenyl)chlorin (m THPC) in human plasma following intravenous infusion is described. The procedure involves extraction of the drug in plasma with methanol/dimethyl sulphoxide (4:1 v/v) containing 5,10,15,20-tetra(p-hydroxyphenyl)chlorin as the internal standard and separation on a C18 reversed phase column with acetonitrile:0.1% trifluoroacetic acid (77:23 v/v) as the mobile phase. The drug was detected specifically and sensitively at its absorption maximum of 423 nm with a detection limit of 15 ng/mL (signal-to-noise ratio of 5). The intra- and inter-assay coefficients of variation (CV) on analysis of a plasma spiked with m-THPC (1 micrograms/mL) were 2.3 and 3.4% (n = 6), respectively. PMID- 8431681 TI - Hydrophobic interaction chromatography of fibroblast proteoglycans. AB - We have investigated the hydrophobic properties of human skin fibroblast proteoglycans and related material by affinity chromatography on Octyl-Sepharose CL-4B in 4 M guanidinium hydrochloride (GdnHCl). Proteoglycans and related material could be separated into non-, medium and highly hydrophobic forms by elution with gradients of Triton X-100 in 4 M Gdn HCl. The non-hydrophobic material included endogenously produced glycosaminoglycan chains and oligosaccharides as well as an HS-proteoglycan with a 35 kDa core. The 65-70 kDa core (glypican-related) proteoglycans appeared among the highly hydrophobic ones, but variable proportions were seen both in the medium and the non-hydrophobic material. Other membrane-bound proteoglycans, like fibroglycan (45 kDa core) and the HS-proteoglycans with 90 and 130 kDa cores, as well as the CS/DS-proteoglycan with a 90 kDa core, were all of high hydrophobicity. There were also indications of a highly hydrophobic CS/DS-proteoglycan with a 45 kDa core. The extracellular proteoglycans, PG-L, PG-S1 and PG-S2, and the HS-proteoglycans with 350 and 250 kDa cores were all of medium hydrophobicity. These proteoglycans emerged in distinct positions when the column was eluted with a gradient of 3-[(3 cholamidopropyl)dimethylammonio]propanesulphonate. PMID- 8431682 TI - Synthesis of novel fluorogenic Edman reagents, 7-N,N-dimethylaminosulphonyl- 4 (2,1,3-benzoxadiazolyl)isothiocyanate (DBD-NCS) and 7-aminosulphonyl-4-(2,1,3 benzoxadiazolyl)isothiocyanate (ABD-NCS). AB - Novel fluorogenic Edman reagents, 7-N,N-dimethylaminosulphonyl-4- (2,1,3 benzoxadiazolyl)isothiocyanate (DBD-NCS) and 7-aminosulphonyl-4-(2,1,3 benzoxadiazolyl)isothiocyanate (ABD-NCS) having no fluorescence themselves were synthesized. The derivatives of amino acids with DBD-NCS fluorescence at 505 nm with excitation at 385 nm. They were separated on a reversed-phase HPLC column and detected at the sub-picomol level. Ala-Phe derivatized with DBD-NCS was cleaved by acid to generate DBD-thiocarbamyl-Ala. PMID- 8431683 TI - Esophageal perforations masked by steroids. AB - Esophageal perforation is usually an acute, life-threatening event, and its diagnosis can be established on the basis of obvious clinical and radiographic findings. This article describes two cases whereby symptoms of esophageal perforations were masked by concomitant administration of steroids, thus causing marked delay in diagnosis and treatment. Esophageal rupture should be considered when patients receiving steroids develop unexplained fever with pleural effusion or pneumomediastinum, particularly following instrumentation or forceful retching. PMID- 8431684 TI - Mucocele of the surgically isolated esophagus. AB - A large esophageal mucocele causing chest pain developed in a 26-year-old woman who had undergone esophageal bypass surgery and gastric interposition because of involvement by scleroderma. Computed tomographic (CT) scans showed the mucocele as an elongated mediastinal mass which spontaneously reduced in size during conservative management. The clinical and radiological features of this unusual postsurgical complication are herein reviewed. PMID- 8431685 TI - Angiographic findings of Meckel's diverticulum: the characteristic appearance of the vitelline artery. AB - Angiographic findings of the vitelline artery in five patients with surgically proven Meckel's diverticulum were reviewed retrospectively. Superselective vitelline arteriography was performed in two patients and superior mesenteric arteriography in three. Arteriography showed the elongated artery without branching originating from the distal ileal artery and a group of tortuous vessels at the distal portion of this artery in all patients. A dense capillary staining of the vitelline artery was exclusively shown in patients with ectopic gastric mucosa. In one patient, injection of methylene blue intraoperatively through a previously placed angiographic catheter into the vitelline artery stained only the vitelline artery and Meckel's diverticulum in blue but neither the mesentery nor the ileum. Demonstration of a nonbranching artery from the ileal artery and a group of dilated tortuous vessels at the distal portion of this artery should suggest the possibility of Meckel's diverticulum and can be confirmed by selective injection of the artery. It should be emphasized that angiography can detect Meckel's diverticulum even in the absence of acute bleeding. PMID- 8431686 TI - Gastrointestinal radiology: current indications and referral patterns. AB - To determine the current indications and referral patterns for routine gastrointestinal radiology examinations, 1000 consecutive patients were prospectively analyzed. The following specialties were the largest sources of referral: general internal medicine (38%), gastroenterology (21%), and general and colorectal surgery (17%). Referrals from gastroenterologists were weighted toward areas not well evaluated by endoscopy, such as suspected small bowel disease. The major indications for upper gastrointestinal (GI) examinations were dysphagia and swallowing disorders (32%), hiatus hernia/reflux (14%), and ulcer (14%). Small bowel series were predominantly performed for inflammatory bowel disease (37%), obstruction (25%), and occult blood loss (18%). The majority of combined upper GI/small bowel studies were performed for indications primarily relating to the small bowel. Forty percent of barium enemas were performed for detection of neoplasms and polyps, with pain/irritable colon (14%) and exclusion of leak (14%) the next most common indications. Traditional indications, such as peptic ulcer disease and neoplastic disease, continue to be sources of referral for gastrointestinal radiology. However, more specialized applications, particularly in areas not well suited to endoscopy, such as swallowing disorders, inflammatory disease of the small bowel, and evaluation of surgical anastomoses, are also being commonly used. The changing indications, along with the previously documented decreased volume of gastrointestinal radiologic procedures, should be kept in mind when planning a radiology resident educational curriculum. PMID- 8431687 TI - Direct invasion of the transverse colon by a cecal tumor. AB - Direct invasion of the transverse colon is known to result from noncontiguous primary tumors spreading along ligamentous attachments or from direct extension of metastatic disease involving the greater omentum. The resultant desmoplastic reaction produces characteristic findings on barium enema. However, to our knowledge, these findings have not been reported to result from extension of a cecal tumor to the transverse colon via the pericolonic fat. We present such a case and discuss the radiographic findings. PMID- 8431688 TI - Sonographic features of tuberculous peritonitis. AB - In order to determine the spectrum of possible sonographic abnormalities in tuberculous peritonitis (TBP), the sonograms of patients with proven disease were compared retrospectively with surgical or laparoscopic findings. The sensitivity of ultrasound for the detection of the various pathologic features of TBP was calculated. Free or loculated intraabdominal fluid, intraabdominal abscess, ileocecal mass, and retroperitoneal lymph node enlargement were most frequently detected by ultrasound. Mesenteric thickening, adherent loops of bowel, and omental thickening may also be seen, but are infrequently detected and should be actively sought in patients in whom the diagnosis is entertained. PMID- 8431689 TI - Intestinal lymphangiectasia: ultrasound evaluation of a case simulating appendicitis. AB - Intestinal lymphangiectasia is a disorder of the lymphatics of the gastrointestinal system that usually manifests itself with protein-losing enteropathy, malabsorption, and ascites. We report an adult patient with this disorder with an unusual presentation simulating an acute abdomen. PMID- 8431690 TI - Endoscopic ultrasound exploration of a choledochal cyst. AB - A 41-year-old man presented with recurrent episodes of pancreatitis in association with a choledochal cyst. Endoscopic ultrasound contributed in making the diagnosis of choledochal cyst. It also revealed the presence of a long common channel, an anomaly involved in the genesis of this congenital malformation of the biliary tree. PMID- 8431691 TI - Focal nodular hyperplasia of the liver: radiologic findings. AB - A retrospective analysis of the results of ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) of 24 cases (28 lesions) of proven focal nodular hyperplasia (FNH) is presented. While US exhibited nonspecific features, CT frequently showed characteristic features: hypodensity on precontrast scans (69%), transient immediate enhancement after bolus injection (96%), and homogeneity (85%). A scar was noted in 31% of the cases. The typical MR triad of isointensity on T1- and/or T2-weighted (T2-WI), homogeneity, and a scar which shows hyperintensity on T2-WI was seen in only 12% of our cases. The most common finding was homogeneity (94%). In two cases the scar was hypointense on T2-WI. To our knowledge, this finding has not been described before. We conclude that the features of FNH, although fairly constant, are at times indistinguishable from those of other hepatic tumors, such as hepatic adenoma (HA), fibrolamellar hepatocellular carcinoma (FLHCC), small hepatocellular carcinoma, and a hyperplastic nodule. Therefore, a multimodality approach is essential for the correct diagnosis in order to prevent unnecessary surgery. PMID- 8431692 TI - Focal periportal liver steatosis. AB - Focal steatosis of the liver may have various appearances on ultrasonography (US) and computed tomography (CT). An unusual case with a macroscopically periportal location is presented and the etiology and differential diagnosis of the condition is discussed. PMID- 8431693 TI - Periportal halo: a CT sign of liver disease. AB - Periportal halos are defined as circumferential zones of decreased attenuation identified around the peripheral or subsegmental portal venous branches on contrast-enhanced computed tomography (CT). These halos probably represent fluid or dilated lymphatics in the loose areolar zone around the portal triad structures. While this CT finding is nonspecific, it is abnormal and should prompt close scrutiny of the liver in search of an underlying etiology. Periportal halos which may be due to blood are commonly seen in patients with liver trauma. Periportal edema may cause this sign in patients with congestive heart failure and secondary liver congesion, hepatitis, or enlarged lymph nodes and tumors in the porta hepatis which obstruct lymphatic drainage. This CT sign has also been observed in liver transplants (probably secondary to disruption and engorgement of lymphatic channels) and in recipients of bone marrow transplants who might develop liver edema from microvenous occlusive disease. While the precise pathophysiologic basis of periportal tracking has not been proven, it represents a potentially important CT sign of occult liver disease. PMID- 8431694 TI - Hookwire localizer as an aid for ultrasonic detection of small liver nodules. AB - We applied a V-shaped localizer and evaluated its clinical usefulness in nine patients with small hepatic nodules less than 2 cm in diameter. A small hepatic nodule was punctured with a 21-gauge localization needle under ultrasonic guidance, and the V-shaped localizer was pushed into the nodule with a wire. The localizer could be observed as a strong echo line by ultrasonography and as a high-density bar by computed tomography (CT). By this method, it was possible to precisely localize the nodule. Intraoperative ultrasonography became less time consuming, and resection of the nodules could be confirmed with low-kilovoltage radiography. PMID- 8431695 TI - Liver lesion detection: comparison between excitation-spoiling fat suppression and regular spin-echo at 1.5T. AB - The role of excitation-spoiling fat suppression (fatsat) imaging in the detection of liver lesions was assessed comparing short TR/TE and lont TR/TE spin-echo (SE) sequences with and without excitation-spoiling fat suppression in 25 patients at 1.5T. The study included patients with liver metastases (n = 21), primary liver cancer (n = 3), and hepatic adenoma (n = 1). Liver lesion detection and lesion liver signal-to-noise ratios (SNR) were determined for the various imaging sequences in a prospective fashion. Liver lesion-liver SNR were highest for long TR/TE (2000-2500/70-80) fatsat images (12.7 +/- 4.8) compared to long TR/TE regular SE (2000-2500/70-80) images (8.8 +/- 5.6) [(p = ns) (not significant)], short TR/TE (200-400/15-20) fatsat images (-6.2 +/- 4.8) (p = 0.05), and short TR/TE regular SE images (-4.9 +/- 3.2) (p < 0.01). Lesion detection was greatest for long TR/TE fatsat (86) followed by long TR/TE regular SE (78) (p = 0.05), short TR/TE fatsat (65) (p < 0.01), and short TR/TE regular SE (60) (p < 0.01). The results of this study suggest that excitation-spoiling fat suppression may improve liver lesion detection and conspicuity. PMID- 8431696 TI - Hepatic arterial resistive indices: correlation with the severity of cirrhosis. AB - Forty-three patients who were scheduled to undergo a percutaneous liver biopsy were evaluated with Doppler sonography to determine the hepatic arterial resistive index (RI). The histologic specimens were graded by a pathologist regarding cirrhosis and inflammation. The specimens demonstrated no cirrhosis in 12 of 43 (28%) patients, early cirrhosis in 10 of 43 (23%), and established cirrhosis in 21 of 43 (49%). Analysis also revealed that inflammation was absent in three of 43 (7%) patients, minimal in seven of 43 (16%), mild in 17 of 43 (40%), moderate in 13 of 43 (30%), and severe in three of 43 (7%). Hepatic artery RIs (without correction for heart rate) ranged from 0.64 +/- 0.06 in patients with early cirrhosis to 0.68 +/- 0.09 in patients with severe inflammation. There was no significant correlation between the degree of cirrhosis and/or inflammation and hepatic artery RI (with or without correction for heart rate). We conclude that Doppler determination of hepatic artery RIs is not a reliable method of predicting the severity of hepatic cirrhosis and/or inflammation. PMID- 8431697 TI - Achalasia associated with hiatal hernia: prevalence and potential implications. AB - Although hiatal hernia is reported with a 40-50% frequency in the general population, its occurrence and potential implications in achalasia are less well known. We reviewed the medical records and radiographic examinations of 120 patients with achalasia to assess the prevalence of hiatal hernia and its importance in evaluation and management of this motility disorder. Hiatal hernia was present in only 10 (8.3%) patients. Age, sex distribution, prevalence of dysphagia and regurgitation, and lower esophageal sphincter pressure measured manometrically were not significantly different in patients having hiatal hernia compared to those without hernia. Most patients (88%) underwent pneumatic dilatation and five esophageal perforations occurred, but all in patients without hiatal hernia. In conclusion, hiatal hernia is uncommon in patients with achalasia for reasons not known. Age, sex, symptoms, and results of esophageal manometry were not significantly different in those with hiatal hernia. Finally, the presence of hiatal hernia is not a contraindication to treatment of achalasia by pneumatic dilatation. PMID- 8431698 TI - Thorotrast-induced ruptured hepatic angiosarcoma. AB - The use of Thorotrast as a contrast medium is now of historical interest. Thorotrast-induced angiosarcoma, though rare, still generates considerable clinical interest because of the characteristic opacification of the liver, spleen, and lymph nodes, and the long latency period between exposure and the onset of the tumor. We present a case of hepatic angiosarcoma which developed 37 years after the administration of Thorotrast. PMID- 8431699 TI - Computed tomography of pyonephrosis. AB - Computed tomographic (CT) findings of 17 pyonephrotic and 20 uninfected hydronephrotic kidneys were reviewed. Parameters evaluated included: renal pelvic wall thickness (none; grade 1, < or = 2 mm; grade 2, 3-5 mm; and grade 3, > 5 mm), renal pelvic contents, parenchymal, and perirenal findings. All patients underwent subsequent percutaneous nephrostomy within 1 week of CT. Common CT findings suggesting pyonephrosis include increased pelvic wall thickness and more severe perirenal fat changes than are seen in uninfected hydronephrosis. However, for any one patient, these findings are often not diagnostic. The presence of clinical signs of infection with hydronephrosis on CT is a more sensitive indicator of pyonephrosis than most CT findings. PMID- 8431700 TI - Metastatic disease of the ureter: patterns of tumoral spread and radiologic findings. AB - The radiographic and sectional imaging features (ultrasound [US], computed tomography [CT], and magnetic resonance imaging [MRI]) of ureteral obstruction due to metastatic disease are reviewed. The radiologic findings depend on the pattern of the tumoral spread: hematogenous submucosal/mucosal metastasis, hematogenous adventitia metastases spreading along periureteral vessels, scirrhous metastatic spread along periureteral vessels, or metastatic spread into lymph nodes with perinodal desmoplastic reaction. Solitary or multiple extraluminal obstructions without substantial displacement of the ureter are characteristic. CT is the examination of choice for morphological analysis. Together with the patient's history and clinical data, a presumptive diagnosis of ureteral obstruction caused by metastatic disease can be made. PMID- 8431701 TI - MR imaging of adrenal lymphoma. AB - A case of lymphoma of the adrenal glands is presented. Both computed tomography (CT) and magnetic resonance imaging (MRI) demonstrated large bilateral adrenal masses with no other associated abdominal abnormalities. MR was better able to demonstrate inferior vena caval patency than CT, and effectively exclude pheochromocytoma as a differential diagnostic consideration due to signal characteristics of the masses. PMID- 8431702 TI - Magnetic resonance imaging of bladder hemangioma. AB - An 18-year-old woman with a bladder hemangioma is described. The tumor had a low signal intensity with multilocular pattern on T1-weighted magnetic resonance (MR) images and high signal intensity on T2-weighted MR images. MR images were useful in evaluating tumor character and its extent. PMID- 8431703 TI - Terminal and intermediate segment lengths in neuronal trees with finite length. AB - A basic but neglected property of neuronal trees is their finite length. This finite length restricts the length of a segment to a certain maximum. The implications of the finite length of the tree with respect to the segment length distributions of terminal and intermediate segments are shown by means of a stochastic model. In the model it is assumed that branching is governed by a Poisson process. The model shows that terminal segments are expected to be longer than intermediate segments. Terminal and intermediate segments are expected to decrease in length with increasing centrifugal order. The results are compared with data from in vivo pyramidal cells from rat brain and tissue cultured ganglion cells from chicken. A good agreement between data and model was found. PMID- 8431704 TI - The differential aspects of the linear isobole in the study of combined action of agents. AB - Although the isobologram is presently the most widely used method of analysis for combined effects of agents, there are several different interpretations of the linear isobole in regard to its use as a criterion of interaction. An investigation of the differential aspects of the linear isobole relation may cast some light in this regard. By conceptual extension of the present single effect level (i.e. effect-point) relation of the linear isobole to an effect neighbourhood relation in which the linear isobole holds over a small continuous range of effect levels, the mathematical differential of the linear isobole can be developed and investigated. This differential aspect provides some useful insights into the implication and interpretation of the linear isobole relation when used as a general criterion in agent interaction studies. It can also serve as the mathematical basis for the formulation of analytic schemes in which the linear isobole relation is applicable over a continuous range of effect levels. PMID- 8431705 TI - Calcium wave propagation by calcium-induced calcium release: an unusual excitable system. AB - We discuss in detail the behaviour of a model, proposed by Goldbeter et al. (1990. Proc. natn. Acad. Sci. 87, 1461-1465), for intracellular calcium wave propagation by calcium-induced calcium release, focusing our attention on excitability and the propagation of waves in one spatial dimension. The model with no diffusion behaves like a generic excitable system, and threshold behaviour, excitability and oscillations can be understood within this general framework. However, when diffusion is included, the model no longer behaves like a generic excitable system; the fast and slow variables are not distinct and previous results on excitable systems do not necessarily apply. We consider a piecewise linear simplification of the model, and construct travelling pulse and periodic plane wave solutions to the simplified model. The analogous behaviour in the full model is studied numerically. Goldbeter's model for calcium-induced calcium release is an excitable system of a type not previously studied in detail. PMID- 8431706 TI - Antibody response to a two-dose regimen of influenza vaccine in allogeneic T cell depleted and autologous BMT recipients. AB - Induction of protective hemagglutination-inhibition (HI) antibodies in response to influenza virus vaccine and the effectiveness of two doses versus a single dose of vaccine were studied in 48 BMT recipients. The patients were 1-50 years old (median 21 years), 33 with malignant and 15 with non-malignant disease. Thirty-five of the patients underwent allogeneic, T lymphocyte-depleted, BMT and 13, autologous BMT. Nine patients had GVHD at initial immunization. The time interval from BMT to influenza vaccination ranged from 2 to 82 months (median 14.5 months). Two doses of vaccine, administered 1 month apart, consisted of trivalent influenza subunit inactivated vaccine with the following strains: A/Singapore/6/86 (H1N1), A/Sichuan/2/87 (H3N2), and B/Beijing/1/87. There was a statistically significant association between development of protective antibody level (> or = 1:40) and the time interval between BMT and initial vaccination (p < or = 0.001). Regression analysis revealed that longer time interval between the BMT and immunization was positively correlated with seroconversion (a fourfold or greater rise in titers). In the presence of GVHD, there was reduced seroconversion to H1N1, but not to H3N2 or B strains. Influenza vaccination within the first 6 months following BMT was totally ineffective. The efficacy of the vaccine was similar to that described in non-immunocompromised hosts initiated 2 years following BMT. As, overall, specific response was only marginally enhanced by the second dose of vaccine, its indication is questionable. PMID- 8431707 TI - Transjugular liver biopsy in BMT. AB - With the aim of evaluating liver disturbances after BMT in 76 patients, the hepatic venous pressure gradient was measured and a transvenous liver biopsy was performed through the jugular vein. Catheterization was successful in 71 patients (93%). In 11 cases the procedure was performed twice, yielding a total number of 82 studies. In five (6%) liver biopsies were non-evaluable. Complications were rare (7%), minor and reversible. As a result of this procedure, the diagnosis was modified in 45%, with both the diagnosis and treatment being modified in 30% of patients. Veno-occlusive disease (VOD) was histologically demonstrated in 15 out of 26 patients (58%) in whom this complication was suspected and in two out of 33 (6%) in whom it was not. Acute GVHD of the liver was confirmed in 15 out of the 35 patients (43%) in whom this complication was suspected and in four of 24 (17%) in whom it was not. The hepatic venous pressure gradient was significantly higher in VOD than in liver GVHD. Whereas 14/17 (82%) patients with VOD had a gradient pressure higher than 9 mmHg, no patient with GVHD had a gradient above this value. We conclude that transjugular liver biopsy is an effective, safe, and useful technique to evaluate BMT related liver dysfunction. PMID- 8431708 TI - Mixed chimerism after sex-mismatched allogeneic BMT: evaluation of two molecular techniques. AB - Two different molecular techniques were used to monitor chimerism following 17 non-T cell-depleted BMTs from female donors to male recipients: pHY10, a Y chromosome-specific probe (Southern or slot blots), and a set of primers for Y chromosome sequence-specific amplification by the polymerase chain reaction (PCR). On Southern blots, male DNA was detectable at a level less than 1% of 10 micrograms DNA while cross-reactivity with autosomal sequences was avoided. On slot blots, male DNA was reliably detectable at levels less than 0.5%, even in small sample (0.5 microgram DNA). With the PCR technique, male DNA was detectable at levels of 1:10(6) to 1:10(7) of 0.5 microgram DNA. Slot blot and PCR results were concordant in 19 of 23 samples. Both techniques demonstrated a constant small mixed chimerism during the first year after BMT and in four of nine patients, this chimerism persisted even longer (up to 29 months after BMT). PMID- 8431709 TI - Anti-pan T lymphocyte ricin A chain immunotoxin (H65-RTA) and methylprednisolone for acute GVHD prophylaxis following allogeneic BMT from HLA-identical sibling donors. AB - Six patients (five children < or = 12 years old and one young adult) underwent allogeneic BMT (not T lymphocyte-depleted) from sex-matched HLA-identical siblings. GVHD prophylaxis consisted of methylprednisolone (30 mg/m2) and anti pan T lymphocyte ricin A chain immunotoxin (H65-RTA) (0.1 mg/kg) administered daily for 12 consecutive doses. H65-RTA was initiated at day +5 (n = 4) or day +2 (n = 2). All patients engrafted. Despite receiving the planned GVHD prophylaxis, all patients developed moderate to severe acute GVHD; five patients developed Grade III/IV GVHD. Four patients died 34 to 78 days post-transplant; GVHD was a contributory cause of death in each case. H65-RTA as used in this study was ineffective for the prophylaxis of acute GVHD. PMID- 8431710 TI - Use of cytosine arabinoside and total body irradiation as conditioning for allogeneic marrow transplantation in patients with acute lymphoblastic leukemia: a multicenter survey. AB - We report the experience of 14 centers which have used the combination of cytosine arabinoside (ara-C; 24-36 g/m2) and total body irradiation (TBI) to prepare 213 patients with acute lymphoblastic leukemia (ALL) for allogeneic BMT. The overall 3-year disease-free survival (DFS) probability is 38% (95% CI: 31 45%); 75 patients died of complications and 51 relapsed. Multivariate analysis identified three factors independently associated with outcome: age, remission/relapse status and patient-donor relationship. The 3-year DFS probability is 52% (41-63%) for the 106 patients aged 0-11 and 25% (16-33%) for the 104 aged 11+ years; the DFS probability was 54% (34-74%), 41% (32-49%) and 19% (5-33%) for those in first remission, later remissions and relapse respectively. Older patients suffered both more toxic deaths and more relapses than young ones. No other covariate was found to predict for outcome. The results using ara-C-TBI are similar to those achieved using cyclophosphamide plus TBI to prepare ALL patients for BMT, perhaps because a seemingly lower relapse rate is offset by more toxic deaths particularly in older patients. Therapeutic trials should focus on reducing toxicity while maximizing antileukemic efficacy, and should stratify for patient and disease-related factors. PMID- 8431711 TI - Thrombotic complications of BMT: association with protein C deficiency. AB - A decrease in levels of circulating anticoagulant protein C has been shown to occur following autologous BMT, and this deficiency may contribute to a hypercoagulable state placing patients at risk for thromboembolic events. We report four patients who suffered a variety of thrombotic complications following BMT (non-bacterial thrombotic endocarditis, superior vena cava thrombosis, thrombotic stroke, purpura fulminans, small bowel infarction secondary to diffuse microvascular thrombosis), which were preceded by or temporally related to decreased levels of protein C. Treatment with fresh frozen plasma (FFP) led to slight, temporary increases in protein C levels but infusions of FFP did not prevent either death or extension of the thrombus in these four cases, suggesting the need for higher protein C doses and/or concomitant anticoagulation. Though no direct causal relationship between these thrombotic complications and the protein C deficiency can be proved, a generalized hypercoagulable state caused by protein C deficiency may have contributed to the development, severity or progression of these complications. PMID- 8431712 TI - Rebound thymic hyperplasia following high dose chemotherapy and allogeneic BMT. AB - We describe a child with acute lymphoblastic leukemia who showed mediastinal widening 8 months after allogeneic BMT. Total thymectomy was carried out by the transcervical approach. Histologic examination showed only thymic hyperplasia. The immunohistologic investigation revealed a normal distribution of thymic cell elements, without evidence of clonal proliferation of lymphocytic subpopulations. This case supports the hypothesis that thymic hyperplasia following chemotherapy may be merely a rebound phenomenon. The patient had an uneventful postoperative recovery and remains in remission more than 1 year after BMT. PMID- 8431713 TI - Immune reconstitution after BMT in children. AB - Serial assessment of peripheral blood T and B cell recovery and serum immunoglobulins was performed in 19 children for the first year following BMT and compared with normal values established from healthy children. Immunophenotypic analysis on bone marrow was performed in selected cases by Southern blotting of the immunoglobulin heavy chain (IgH) gene. We found no significant differences between T cell-replete or depleted allogeneic bone marrow transplants. Lymphocyte numbers were low until 9 months post-BMT. T cell numbers (CD2, CD3, CD5) were also low until 12 months but B cell numbers (CD19) became normal at 3 months. Both CD4+ and CD8+ T cell subsets were low post-BMT with depression of CD4+ greater and more prolonged than that of CD8+. No overshoot of CD8+ was seen. The principal effect of GVHD or its treatment was further depression of CD4+ cells but with no increase in CD8+; recovery of B cells was also delayed. Recovery of IgG was slow with only six of 11 children reaching an age-adjusted normal level by 1 year, whereas there was more rapid recovery of IgM and IgA. Several children had an increase in lymphocytes of immature appearance in their bone marrow at varying times post-BMT with increased cells of phenotype CD19+, CD10+, HLA-DR+ and TdT+. In each case Southern blotting showed a germline pattern of the IgH indicating a polyclonal early B cell regenerative population. PMID- 8431714 TI - Fanconi's syndrome due to ifosfamide. AB - Although renal wasting of phosphate is relatively common, Fanconi's syndrome following ifosfamide chemotherapy is rare. This case illustrates the possibility of developing Fanconi's syndrome despite the apparent lack of toxicity during previous ifosfamide exposure. As the use of high-dose ifosfamide-containing regimens prior to BMT increases, the occurrence of this adverse effect may become more frequent. Morbidity due to Fanconi's syndrome can be decreased by close monitoring and aggressive management of fluid and electrolytes. PMID- 8431715 TI - Total lymphoid irradiation for treatment of drug resistant chronic GVHD. AB - We report our experience with total lymphoid irradiation (TLI) in three patients with GVHD which had failed to respond to standard drug treatment. The clinical manifestations of GVHD markedly improved with TLI treatment. PMID- 8431716 TI - Successful second unrelated donor BMT in a child with juvenile chronic myeloid leukaemia: documentation of chimaerism using the polymerase chain reaction. AB - A 3-year old child with juvenile chronic myeloid leukaemia received a T cell depleted BMT from a male unrelated donor. There was early graft failure associated with increasing splenomegaly and hypersplenism. Splenectomy was performed 53 days post-transplant and was followed by autologous marrow recovery with return of leukaemia. A second unrelated donor BMT was performed 9 months later using T cell-replete marrow from a similarly matched female donor. Grade 2 GVHD involving the skin and gut responded to treatment with steroids. Chimaerism was assessed using Y-specific polymerase chain reaction (PCR) and microsatellites. Samples taken at the time of splenectomy showed no donor marrow engraftment but there was significant engraftment in the spleen. Following the second transplant, donor-type haematopoiesis was documented using a panel of microsatellite probes. The patient remains well 6 months after transplant. Splenectomy should be considered prior to transplant in patients with significant splenomegaly and hypersplenism. Partial chimaerism in the spleen, but not bone marrow, post-BMT, has not previously been documented. PCR technology is a useful and highly sensitive way to assess chimaerism post-BMT and is informative in sex matched cases, whilst the small amount of material required is advantageous in paediatric patients. PMID- 8431717 TI - Mixed leukocyte culture reactivity, HLA-DP typing and GVHD. PMID- 8431718 TI - High dose chemotherapy for children with brain tumours. PMID- 8431719 TI - The health of the nation. Coronary heart disease and stroke. PMID- 8431720 TI - The health of the nation. Cancers. PMID- 8431721 TI - The health of the nation. Mental illness. PMID- 8431722 TI - The health of a nation. Accidents. PMID- 8431723 TI - The health of the nation. HIV/AIDS and sexual health. PMID- 8431724 TI - Pathophysiology of muscular dystrophy. AB - The inevitable and remorseless clinical decline in a patient with Duchenne muscular dystrophy (DMD) evokes a special sense of impotent desperation, which was, until recently, exacerbated by lack of obvious progress in its treatment. However, identification of the culpable gene has provided insight into the pathogenesis of DMD and glimmerings of hope for its treatment. PMID- 8431725 TI - Radiological diagnosis and staging of primary bronchogenic carcinoma. AB - Bronchogenic carcinoma remains the commonest fatal malignancy worldwide. In this paper we discuss the various imaging modalities available to aid diagnosis and staging, presenting these techniques in a clinical sequence. We also consider some of their limitations. PMID- 8431726 TI - Drug use in pregnancy. AB - Drug use is on the increase and it impinges on many areas of clinical practice, posing complex management problems. It often provokes strong reactions--and never more so than when it involves pregnant women, with consequent implications for fetal wellbeing. In this emotive area we must objectively identify the real problems and distinguish clearly between medicine and morality. PMID- 8431727 TI - Clozapine. AB - Clozapine is an atypical agent for intractable schizophrenia which was introduced into the UK at the beginning of 1990. Its lack of extrapyramidal side effects and its action on negative symptoms single it out from conventional neuroleptics. This article describes the drug's development/special monitoring and dispensing arrangements, and gives advice on how it can best be utilized. PMID- 8431728 TI - Decision making in surgery: management of a leaking gastrointestinal anastomosis. AB - A leaking anastomosis is a rare though important complication of abdominal surgery, but when it occurs a series of important decisions have to be made to ensure successful treatment. Surgery forms only a small part of its management and the trainee must understand the principles involved in the care of such a case. PMID- 8431729 TI - Government gnaws at NHS core. PMID- 8431730 TI - Doctors feel sharp end of media scalpel. PMID- 8431731 TI - Problems encountered by women GPs. PMID- 8431732 TI - Problems encountered by women GPs. PMID- 8431734 TI - The health of the nation. Overview. PMID- 8431733 TI - Psychiatric disorders in Parkinson's disease. PMID- 8431735 TI - A morbidity review of children with complete unilateral cleft lip nose at 10 +/- 1 years of age. AB - A retrospective study of morbidity due to primary radical nasal correction was undertaken on 33 consecutive cases of complete unilateral cleft lip and palate within one year of their 10th birthday. Primary surgery was performed by one surgeon (RWP) using the Alar Leapfrog technique. Morbidity was assessed by the number of manoeuvres required for revisional surgery up to the age of 10 and was derived from the case notes. A total of 12 patients required no revision. The number of revisional manoeuvres was 39 in 27 anaesthetic sessions. Cleft lip noses treated by a technique of primary radical nasal correction (Alar Leapfrog) required a significant number of secondary manoeuvres to produce an acceptable result. This must be balanced against reduced teasing due to improved symmetry over this period. PMID- 8431736 TI - A comparison of computer versus panel assessment of two groups of patients with cleft lip and palate. AB - A computer-based system of assessing asymmetry was used to compare standardised photographs of primarily corrected cleft noses, uncorrected cleft noses and control (normal) noses. A significant difference was found between control and cleft groups for both upper nasal perimeter (p < 0.001) and nostril outline (p = 0.001), and between uncorrected and corrected noses for upper nasal perimeter (p = 0.03) but not for nostril outline (p = 0.99). Comparing the results achieved by panel assessment (Cussons et al., 1992) with this of the same patients revealed some discordance related to the influence of extraneous factors on panel decisions. Panel assessment is needed in the evaluation of overall appearance, whilst the computer method is able to assess the results of different techniques, and from different centres, on specific features where symmetry is a major objective of surgical technique. PMID- 8431737 TI - The pursuit of function and cosmesis in managing oral cancer. PMID- 8431738 TI - Reconstruction of the cervical trachea with a free forearm flap. AB - With the aim of voice restoration after repair of a total defect or obstruction of the cervical trachea, we developed a new method of total cervical tracheal reconstruction with a free forearm flap. The forearm flap is inverted to form a tube and then interposed between the subglottic trachea and an adjacent cutaneous fistula created at the upper portion of the tracheostoma. A permanent tracheostoma is preserved, and an L-shaped silicone tube is inserted in the reconstructed cervical trachea and the tracheostoma as a stent. In two patients, both became able to speak. PMID- 8431739 TI - Orbital neurofibromatosis with enophthalmos. AB - Two patients with orbital neurofibromatosis associated with enophthalmos are presented. Assessment using 3D-CT scan shows an increase in the size of the orbital cavity and an enlargement of the inferior orbital fissure, which allows orbital fat to prolapse into the infratemporal fossa, causing enophthalmos. PMID- 8431740 TI - Progressive hemifacial atrophy (Romberg's disease): skeletal involvement and treatment. AB - Progressive hemifacial atrophy (Romberg's disease) manifests variable involvement of the skin, soft tissue and underlying cranio-facial skeleton. Significant bony deformation has been identified in those patients with early onset disease, the result of factors both intrinsic to the disease process and secondary to the abnormal environment in which the skeleton develops (functional matrix). Treatment demands combined osteotomy and augmentation of the skeleton in concert with conventional approaches to soft tissue correction. PMID- 8431741 TI - Secondary vascularised hair-bearing island flaps for eyebrow reconstruction. AB - Reconstruction of the eyebrows using a vascularised hair-bearing island flap is presented. The quality, density and direction of growth of hair for reconstruction of the eyebrows can be selected by using free vascular bundle transfer to prepare a secondary vascularised island flap. PMID- 8431742 TI - An experimental study of delay of flow-through venous flaps. AB - A delayed procedure was performed in flow-through venous flaps made in rabbits' ears. Compared with undelayed venous flaps, the delayed flaps at 7, 14 and 21 days after delay showed a distinct increase of survival area. This effect increased with the delay period. PMID- 8431743 TI - The arterialised venous flap: experimental studies and a clinical case. AB - It is accepted that small arterialised venous flaps (AVF) can survive on a recipient bed with poor blood supply but survival of larger flaps is not always satisfactory. Possible reasons for this include the flap anatomy, particularly the pattern of the venous network, or factors at the recipient site. To investigate the possible factors in the flap design and the recipient site of an arterialised venous flap, we studied the relationship between (1) size of the artery used to arterialise the flap at the recipient site and the survival rate and (2) the number of draining veins and the survival rate, using rabbit ear skin flap models. Our results suggest that AVFs may become necrotic in the presence of a relative excess of arterial blood inflow, and that two exit veins are more effective than one. We also report a case where a 10 x 15 cm sized free AVF harvested from the lower extremity survived on the forearm. PMID- 8431744 TI - The pedicled venous flap. Clinical applications. AB - Experimental findings of survival of pedicled venous flaps were clinically applied in seven cases for traumatic skin defects on digits. Five flaps which were transferred to or on digits other than the thumb survived, but two flaps from the index to the thumb developed partial necrosis. In order to prevent flap necrosis, the draining vein should be short. PMID- 8431745 TI - A panel based assessment of early versus no nasal correction of the cleft lip nose. AB - There is a need to be able to assess the overall result in a significant series of cases of a method of management of the cleft lip and nose deformity in order to avoid "best case" reporting often used to introduce new techniques. The present study was performed by a panel placing standardised base view photographs in rank order. The photographs were of 10-year-old subjects of whom 15 were normal controls, 22 were from the Rikshospitalet, Oslo, all of whom had no primary nasal correction and 25 from Frenchay Hospital, Bristol, who all had radical primary nasal correction. Ranking was performed for upper nasal perimeter symmetry, nostril outline symmetry and for overall aesthetic appearance. Analysis of the results showed a significant difference between the three groups, with the corrected noses showing better symmetry. Inter and intraobserver correlations were very close. The limitations of a ranking and marking method of panel assessment are discussed, and a computerised method is presented in subsequent papers. PMID- 8431746 TI - Cutaneous melanoma: pathological certainties and uncertainties. AB - A historical review is given of the role of histopathology as a prognostic guide to the behaviour of cutaneous melanomas. Problems in the assessment of some of the current parameters are outlined in an attempt to explain the difficulties faced by histopathologists with some types of melanoma. PMID- 8431747 TI - Pain-temperature relation in the application of local anaesthesia. AB - One hundred and thirty-six patients attending for local anaesthetic procedures in the trigeminal area were assigned to four groups. Each group was injected with the anaesthetic solution at temperatures 10 degrees C, 18 degrees C, 37 degrees C and 42 degrees C, respectively. Measurement of pain during injection was made on a numeric scale. The results show a strong relationship between the temperature of the anaesthetic solution and the pain of the injection (p << 0.001). This demonstrates that warming the anaesthetic solution significantly reduces the pain felt by the patient during injection, especially at 42 degrees C. PMID- 8431748 TI - Comparing DuoDERM E with scarlet red in the treatment of split skin graft donor sites. AB - A prospective, randomised, controlled study compared DuoDERM E (DE) with scarlet red (SR) in the treatment of split skin graft donor areas in 60 patients. Healing and donor site comfort were significantly better in the DE group. There was no clinical infection in either group. The wound leakage rate was higher in the DE group, requiring an average of 0.8 replacement dressings per donor site as compared with an average of 0.04 for the SR group. An estimate of the cost per donor site for the first ten days of dressing is given. PMID- 8431749 TI - A comparison of Zenoderm with DuoDERM E in the treatment of split skin graft donor sites. AB - A prospective, randomised, controlled study compared Zenoderm (ZM) with DuoDERM E (DE) in the treatment of split skin graft donor areas in 64 patients. The donor site comfort was similar in the two groups. DE usage resulted in significantly faster healing but also a higher leakage rate than ZM. Two patients in the ZM group developed infection in their donor sites. The cost is significantly less with ZM than DE. PMID- 8431750 TI - Chondrosarcoma following free fibula transfer for non-union of the tibia. PMID- 8431751 TI - Bilateral heel pad hypertrophy. PMID- 8431752 TI - Volumetric analysis of the telencephalon and tectum during metamorphosis in a flatfish, the turbot Scophthalmus maximus. AB - The telencephalic hemispheres and the optic tectum of the turbot Scophthalmus maximus were analysed volumetrically during metamorphosis. Both brain regions develop an asymmetry coordinated chronologically with metamorphic events that produce asymmetry in the rest of the animal. Furthermore, the brain asymmetries are correlated with, and may be determined by, the side of origin of their primary afferent inputs, such that the more voluminous side of the brain receives these inputs from the zenithal side. After metamorphosis, the telencephalon remains asymmetric, whereas the optic tectum recovers its bilateral symmetry. PMID- 8431753 TI - Sound detection and processing by fish: critical review and major research questions. AB - The literature on fish hearing has increased significantly since our last critical review in 1973. The purpose of the current paper is to review the more recent literature and to identify those questions that need to be asked to develop a fuller understanding of the auditory capabilities and processing mechanisms of fishes. We conclude that while our understanding of fish hearing has increased substantially in the past years, there are still major gaps in what we know. In particular, the comparative functional literature is extremely limited, and we do not yet know whether different species, and particularly hearing specialists as compared to hearing nonspecialists, have fundamentally different auditory capabilities and mechanisms. PMID- 8431754 TI - The role of the cerebellum in motor control and perception. AB - The cerebellum has an important role in control and coordination of movements, but in some species, notably weakly electric fish of the family Mormyridae, anatomical, electrophysiological and behavioural evidence indicates that parts of cerebellar cortex are concerned with tracking movements of objects around the animal, rather than with controlling movements of the animal itself. The existence of such anomalies suggests that the cerebellum may not be exclusively, or even primarily, a structure for motor control. Evidence reviewed in this paper shows that the cerebellum is associated with sensory systems used for tracking movements of targets in the environment, as well as movements made by the animal itself, in all vertebrates, not just in a few isolated cases. The evidence indicates that the standard theory that the function of the cerebellum is control and coordination of movements only partially characterises cerebellar function. The cerebellum may be better characterised as a tracking system, with an important role in control and coordination of movements which arises because of an animal's need to track moving objects, to track its own movements, and to analyse the sensory consequences of movements in order to control movements. This theory not only predicts the known motor consequences of cerebellar dysfunction, it also predicts a specific kind of perceptual deficit caused by cerebellar dysfunction, namely an inability to accurately follow and predict trajectories of objects moving in the environment. A variety of behavioural and perceptual tasks in addition to motor control and movement tracking may require dynamical state estimation, and therefore may involve the cerebellum. PMID- 8431755 TI - Wally Welker: a career in relating brains, behaviors, and evolutions. PMID- 8431756 TI - A morphological study of the principal and accessory abducens nuclei in the caspian terrapin (Mauremys caspica). AB - The location of principal and accessory motoneurons and principal interneurons of the nucleus abducens was determined in the caspian terrapin (Mauremys caspica) by means of horseradish peroxidase histochemical tracing. Enzyme injections were made into the ipsilateral lateral rectus and retractor bulbi muscles and into the contralateral oculomotor nucleus. Labeled principal abducens motoneurons formed a cluster of cells in the rhombencephalon, under the IVth ventricle and adjacent to the medial longitudinal fascicle. The accessory abducens motoneurons were located more deeply in the rhombencephalon and more ventrolaterally than the principal motoneurons forming a compact aggregation of neurons. The principal interneurons of abducens nucleus were arranged as a cluster of cells under the floor of the IVth ventricle and more lateral than the principal motoneurons, with no intermingling. PMID- 8431757 TI - Neurons located in the trigeminal sensory complex and the lateral pontine tegmentum project to the oculomotor nucleus in the rabbit. AB - Neurons located in the trigeminal sensory complex (TSC) and the lateral pontine tegmentum (LPT) have been reported to project to both the accessory abducens and the facial nuclei, which innervate the retractor bulbi and orbicularis oculi muscles respectively, in order to control the nictitating membrane (NM) and eyelid defensive reflex. Since muscles innervated by the oculomotor nucleus (OCM) also appear to be involved in this reflex, retrograde and anterograde tracers were used in this study to determine whether there are projections from the TSC and LPT to the OCM in the rabbit. Injections of horseradish peroxidase (HRP) in the OCM nucleus labeled neurons in the LPT surrounding the trigeminal motor nucleus dorsally, laterally and ventrally. Only a few scattered neurons were found in the principal and spinal trigeminal nuclei. Injection of biocytin in the LPT area containing most of the HRP-labeled neurons caused anterograde labeling of fibers that crossed the midline and ascended just dorsal to the contralateral medial lemniscus. A proportion of these fibers coursed in a dorsal direction to enter and terminate within the OCM contralateral to the injection site. The location of the motoneuronal groups innervating the different extraocular muscles was studied by retrograde transport of HRP, and compared with the distribution of biocytin-labeled terminals. It was found that the terminals were located in the superior rectus and the levator palpebrae zone of the nucleus. We discuss the functional significance of this projection for the eyelid and NM response. PMID- 8431758 TI - Origin of intracellular Ca2+ elevation induced by in vitro ischemia-like condition in hippocampal slices. AB - Microfluorometry was used to investigate the origin of intracellular Ca2+ ([Ca2+]i) elevation in field CA1 of gerbil hippocampal slices perfused with a glucose-free physiological medium equilibrated with a 95% N2/5% CO2 gas mixture (standard in vitro ischemia-like condition). Large [Ca2+]i elevation was detected about 4 min after the beginning of standard in vitro ischemia-like condition, which was accompanied with a negative shift of extracellular DC potential. When slices were perfused with Ca(2+)-free in vitro ischemia-like medium, large [Ca2+]i elevation was observed about 3.5 min after the beginning of Ca(2+)-free in vitro ischemia-like condition, however, the increase in [Ca2+]i was more gradual and of a lesser extent compared with that detected in the slices perfused with the standard in vitro ischemia-like medium that contained Ca2+. When slices were perfused with the Ca(2+)-free in vitro ischemia-like medium that contained dantrolene (50 microM) which is known to prevent Ca(2+)-induced Ca2+ release from intracellular Ca2+ stores, the increase in [Ca2+]i was more gradual and of a lesser extent compared with that detected in the slices perfused with the Ca(2+) free in vitro ischemia-like medium that did not contain dantrolene. These results indicate that large [Ca2+]i elevation induced by in vitro ischemia-like condition in field CA1 of the hippocampus was caused by both Ca2+ influx from extracellular space and Ca2+ release from intracellular Ca2+ stores, and that a part of the Ca2+ release was due to Ca(2+)-induced Ca2+ release from intracellular Ca2+ stores. PMID- 8431759 TI - Decreased heterosynaptic and homosynaptic paired pulse inhibition in the rat hippocampus as a chronic sequela to limbic status epilepticus. AB - We studied a rat model of chronic epilepsy that shares key features with certain patients with temporal lobe epilepsy. This model relies on a previous period of limbic system status epilepticus established by focal stimulation to one hippocampus. Animals were examined 1 month after recovery from such status epilepticus and compared to unstimulated controls and to animals that received stimulation but did not develop status epilepticus. Two experimental procedures were employed to study changes in paired pulse inhibition of population spike (PS) discharges elicited in CA1 pyramidal cells. One procedure (homosynaptic) delivered two identical stimuli to the CA3 region contralateral to the recording site; the other procedure (heterosynaptic) delivered a conditioning stimulus to the ipsilateral angular bundle and a separate test stimulus to the contralateral CA3. For both procedures, influences of stimulus intensities and of interpulse intervals on the potency of paired pulse inhibition were determined. Based on the results, standardized protocols that assayed the maximal amount of paired pulse inhibition were developed. With the homosynaptic protocol, there was one period of inhibition (interpulse intervals up to 300 ms). Animals that previously experienced limbic status epilepticus had markedly less paired pulse inhibition under these conditions than did controls. The stimulated, non-status epilepticus animals were not different from controls. For the heterosynaptic protocol, there were 2 phases of paired pulse inhibition, early (< 50 ms) and late (> 300 ms), separated by a period of paired pulse facilitation. After status epilepticus there were, compared to controls, decreases in both early and late phases of inhibition. The stimulated, non-status epilepticus animals were not different from controls. For the paired pulse facilitation, there was no difference between the animals that experienced status epilepticus and controls. These findings indicate a profound and enduring disturbance of GABA-mediated inhibition in this model. The heterosynaptic paired pulse protocol deals with a number of confounding issues associated with the homosynaptic protocol in this regard. Furthermore, the results suggest the inhibitory disturbance is diffuse, affecting various inhibitory circuits in the hippocampus. PMID- 8431760 TI - Distribution of guanine nucleotide-binding protein in the brain of the reeler mutant mouse. AB - The localization of a GTP-binding protein (G(o)) in the cerebellar and cerebral cortex and hippocampus of the normal and reeler mutant mouse was immunohistochemically examined using affinity-purified antibody raised against the alpha subunit of G(o). Although the general distribution pattern of G(o) immunoreactive products in the brain of the normal mouse, i.e., abundant in the neuropil but absent from neuronal cell bodies, is also seen in the reeler brain, some differences are present, as described below. Strong G(o)-immunoreactive products are found in the molecular layer of the cerebellar cortex of the normal mouse. In the reeler cerebellum, in addition to the strong G(o)-immunoreactivity of the thin molecular layer, moderate G(o)-immunoreactivities are also found in the granular cell layer and the central cerebellar mass. G(o)-immunoreactive products are distributed throughout all layers of the cerebral cortex of the normal and reeler mouse. However, layer I of the normal cerebral cortex is more strongly stained with this antibody than the underlying layers, whereas the upper third of the reeler cerebral cortex is more strongly stained than the lower two thirds. In the hippocampus of the normal mouse, G(o)-immunoreactive products are localized in the neuropil of the stratum oriens, stratum radiatum and stratum lacunosum-moleculare, but absent from the cell bodies of the pyramidal cells and their apical dendritic shafts. Such a distribution pattern of G(o)-immunoreactive products is also seen in the hippocampus of the reeler mouse, except that G(o) immunonegative pyramidal cells split into 2 or 3 laminae.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431761 TI - Cysteine proteinases in rat dorsal root ganglion and spinal cord, with special reference to the co-localization of these enzymes with calcitonin gene-related peptide in lysosomes. AB - To examine the localization of lysosomal cysteine proteinases, cathepsins B, H, and L, and their correlation with a neuropeptide, calcitonin gene-related peptide (CGRP) in nerve cells, immunocytochemistry was applied to rat dorsal root ganglion (DRG) and spinal cord (SC) of lumbar segments. By light microscopy, granular immunodeposits for cathepsins B and L were localized in small and large nerve cells in DRG and SC. The cathepsin B- and L-positive smaller nerve cells in DRG and large nerve cells in the ventral horn of SC were also immunostained by anti-CGRP. By electron microscopy, nerve cells in DRG and SC contained lysosomes labeled by immunogold particles indicating cathepsins B and L, while immunogold particles for cathepsin L labeled lysosomes of glial cells. Double immunostaining co-localized immunogold particles for cathepsin B or L and CGRP in lysosomes of small nerve cells in DRG and motoneurons in SC. Moreover, cathepsin H was immunocytochemically demonstrated in lysosomes of satellite cells in DRG, while lysosomes of perivascular microglia-like cells were labeled by immunogold particles for cathepsins B, H, and L. The results suggest the possibility that lysosomes in nerve cells participate in regulation of intraneuronal CGRP level by degrading CGRP. PMID- 8431762 TI - Binding of secreted human neuroblastoma proteoglycans to the Alzheimer's amyloid A4 peptide. AB - Proteoglycans (PGs) may play a fundamental role in all forms of amyloidosis. In Alzheimer's disease, proteoglycans are found deposited in senile plaques and in neurofibrillary tangles. However, the cellular source of these deposited PGs and their role in amyloidosis in Alzheimer's disease is unknown. Proteoglycans were purified from conditioned medium of human neuroblastoma cells (SKNSH-SY 5Y). Two species of proteoglycans were identified by enzyme susceptibility including a heparan sulfate proteoglycan and a dermatan sulfate proteoglycan. A monoclonal antibody to the protein core of a vascular basement membrane heparan sulfate proteoglycan found in senile plaques in Alzheimer's disease cross-reacted with the proteoglycans secreted by human neuroblastoma cells. Binding between 35SO4 labelled neuroblastoma proteoglycans and the Alzheimer amyloid (A4) peptide was demonstrated by affinity chromatography. Specificity studies demonstrated that binding of human neuroblastoma proteoglycans to the amyloid peptide was specific for a heparan sulfate glycosaminoglycan, with some binding to a dermatan sulfate proteoglycan. Binding to A4 was also demonstrated by a chemically deglycosylated protein core preparation. No significant binding of neuroblastoma proteoglycans was found to two other basic peptides derived from the extracellular domain of the beta-amyloid precursor, demonstrating the specificity of proteoglycan binding to the A4 peptide. Human neuroblastoma proteoglycans may bind to the-Alzheimer amyloid A4 peptide in a region with a heparin binding consensus sequence [VHHQKL] which also contains the cleavage site of the beta-amyloid precursor protein. Neuronal proteoglycans may either regulate the secretion of the amyloid protein precursor or modify the binding of the amyloid protein precursor to other cellular adhesion molecules. Alterations in this binding may be related to the pathogenesis of amyloid deposition in Alzheimer's disease. PMID- 8431763 TI - Lack of the carboxyl terminal sequence of tau in ghost tangles of Alzheimer's disease. AB - Using seven independent antibodies against the amino terminal to the carboxyl terminal sequence of tau, we biochemically analyzed and compared the neuropathogenesis of two Alzheimer's disease brains from the viewpoint of abnormal processing on tau, the major constituent of paired helical filaments. One showed typical Alzheimer's disease with senile plaques and intracellular neurofibrillary tangles. The other showed advanced Alzheimer's disease with senile plaques and virtually the sole of ghost tangles without intracellular neurofibrillary tangles. We confirmed the previous observation that the carboxyl thirds of tau are tightly associated with paired helical filaments isolated in the presence of SDS. We found that biochemically, ghost tangles were abnormally phosphorylated and lacked the final carboxyl terminal sequence as well as the amino half of tau, unlike intracellular tangles. From these biochemical results taken together with the current evidence for ubiquitin in ghost tangles, we concluded that ghost tangles were extensively processed and irreversibly transformed into highly insoluble extracellular deposits. PMID- 8431764 TI - Temporal profile of the induction of heat shock protein 70 and heat shock cognate protein 70 mRNAs after transient ischemia in gerbil brain. AB - Distributions of heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 mRNAs after 2, 5 and 15 min of transient global ischemia in gerbil forebrain were investigated by in situ hybridization using cloned cDNA probes selective for each mRNA species. Morphological studies were also performed at the dorsal hippocampal level of coronal sections from the identical brains until 7 days after the reperfusion. Following 2 min of ischemia, HSP70 and HSC70 mRNAs were induced together in hippocampal dentate granule cells at 1 and 3 h of the reperfusion. No histological change was observed in brain cells. Following 5 min of ischemia, HSP70 and HSC70 mRNAs were induced in all hippocampal cells. The induction of HSP70 mRNA in hippocampal CA1 cells sustained until 2 days, while that of HSC70 mRNA declined gradually. Only CA1 cells were lost at 7 days of the reperfusion. Following 15 min of ischemia, the mRNAs were induced in more extensive brain regions including neocortex and thalamic nuclei. In hippocampal CA1 cells, inductions of HSP70 and HSC70 mRNAs diminished by 2 days corresponding with the neuronal damage. HSC70 mRNA induction was not so much as HSP70 mRNA induction especially in hippocampal CA1 and thalamic cells. Our results showed that HSP70 and HSC70 mRNAs were generally induced together after transient ischemia, but that the inductions were spatially and chronologically different after different periods of ischemia. The dissociation of the induction was also found in cells severely injured after 5 and 15 min of ischemia. PMID- 8431765 TI - Monoamine concentrations in rat prefrontal cortex and other mesolimbocortical structures in response to partial neonatal lesions of the medial prefrontal cortex. AB - In an earlier study it was found that partial neonatal lesions of the medial prefrontal cortex (mPFC) resulted in an increased dopaminergic innervation in the remaining part of mPFC along with functional sparing. The present study assessed whether this response is restricted to this part of the cortex or whether also other structures of the mesolimbocortical system are involved. Furthermore, it was investigated whether the other monoaminergic systems were affected by neonatal mPFC lesions. In 6-day-old rats, the mPFC was partially ablated or a sham operation was made. The concentrations of dopamine (DA) and its metabolites increased to 250-350% in the remaining part of the mPFC compared to the sham operated controls. The response was most prominent in this part of the cortex; no other mesolimbocortical structure showed such major changes of DA and its metabolites. In addition, a small increase in the concentrations of noradrenaline, serotonin and their metabolites was also spotted in the remaining mPFC and some other mesolimbocortical structures of the lesioned animals. The present data support the suggested involvement of DA in the neural mechanism of sparing of function, and this DA response seems to be most prominent in the remaining mPFC. However, the responses of the noradrenergic and serotonergic systems may also be important for sparing of function to occur. PMID- 8431766 TI - Female sexual behavior following intracerebral infusion of the 5-HT1A agonist, 8 OH-DPAT, into the medial preoptic area. AB - The effects of intracerebral infusions of the 5-HT1A agonist, 8-hydroxy-2-(di-n propylamino)tetralin (8-OH-DPAT), on sexual behaviors of intact, proestrous rats were examined. When administered into either the rostral or the caudal portions of the medial preoptic area (mPOA), bilateral infusions of 200, 500, or 2,000 ng of 8-OH-DPAT reduced lordosis behavior (e.g. the lordosis/mount ratio; L/M) and increased the female's resistance to the male's attempts to mount. Infusions within the mid-rostrocaudal mPOA failed to suppress lordosis behavior but were as effective as the rostral or caudal infusions in the elicitation of resistive behavior. A reduction in the L/M ratio was usually accompanied by a slight decline in the quality of the lordosis reflex; proceptivity, as evidenced by the occurrence of hopping and darting behavior, was not consistently reduced by 8-OH DPAT. In fact, 4 out of 7 rats that received mid-rostrocaudal infusions of 8-OH DPAT showed a "frenzied" accentuation of hopping and darting behavior. These results suggest that 5-HT1A receptors in the mPOA play an important role in several components of female sexual behavior. The identification of a rostral and caudal location of mPOA sites where 8-OH-DPAT suppressed lordosis behavior is consistent with the organization of 5-HT fibers in the mPOA and with ventromedial hypothalamic (VMN) input into the mPOA. PMID- 8431767 TI - Long-lasting decrease in dopamine uptake sites following repeated administration of methamphetamine in the rat striatum. AB - We investigated the effects of repeated administration of methamphetamine on dopamine (DA) uptake sites in the rat striatum by using an increasing dose paradigm of methamphetamine (2.5 mg/kg on day 1; 5 on day 3; 7.5 on day 5 and 10 on day 7), each being given twice on the indicated day by s.c. injection. It has been established that this administration paradigm produces distinct sensitization in methamphetamine-induced behavior. A 36% reduction in specific [3H]DA uptake, and a 29% reduction in specific [3H]GBR12935 binding in the striatum were demonstrated in rats sacrificed 7 days after the last methamphetamine administration. A similar reduction in striatal [3H]GBR12935 binding sites was observed even 30 days after discontinuation of the drug. These data indicate that this treatment regimen of gradually escalating doses of methamphetamine induces a long-lasting decrease of DA uptake sites in rat striatum. PMID- 8431768 TI - Cultures of ensheathing cells from neonatal rat olfactory bulbs. AB - We have derived highly enriched populations of ensheathing cells (ECs) from the olfactory nerve layer of neonatal rat olfactory bulbs. Contaminating cells, such as fibroblasts, were eliminated from EC cultures by cytosine arabinoside and immunoadsorption with antiserum to Thy-1.1. At the same time, ECs were stimulated to divide by the addition of bovine pituitary extract into the culture media. Confluent cultures containing 96-99% ECs, were comprised of either spindly bipolar cells or cells bearing multiple processes oriented on opposite poles. The ECs immunostained positively for GFAP, S-100 protein, N-CAMs and Neu 5, and were negative for the presence of neurofilaments. Scanning and transmission electron microscopy showed that the ultrastructure of the ECs resembled that in vivo. The nucleus was irregular in shape, intermediate filaments were usually scattered throughout the cytoplasm instead of being grouped into bundles, and rough endoplasmic reticulum existed as isolated expanded profiles. PMID- 8431769 TI - Differential development of cholinergic nerve terminal markers in rat brain regions: implications for nerve terminal density, impulse activity and specific gene expression. AB - During critical developmental periods, cholinergic activity plays a key role in programming the development of target cells. In the current study, ontogeny of cholinergic terminals and their activity were contrasted in 4 brain regions of the fetal and neonatal rat using choline acetyltransferase activity, which is unresponsive to changes in impulse flow, and [3H]hemicholinium-3 binding, which labels the high-affinity choline transporter that upregulates in response to increased neuronal stimulation. In all 4 regions (cerebral cortex, midbrain + brainstem, striatum, hippocampus) choline acetyltransferase activity increased markedly from late gestation through young adulthood, but generally did so in parallel with the expansion of total membrane protein, reflective of axonal outgrowth and synaptic proliferation. In contrast, [3H]hemicholinium-3 binding was extremely high in late gestation and immediately after birth, declined in the first postnatal week and then rose again into young adulthood. The ontogenetic changes reflected alterations primarily in the number of binding sites (Bmax) and not in binding affinity. Only the latter phase of development of [3H]hemicholinium-3 binding corresponded to the ontogenetic changes in choline acetyltransferase activity; in the hippocampus, there were disparities even in young adulthood, where [3H]hemicholinium-3 binding showed a spike of activity centered around the 5th to 6th postnatal week, whereas choline acetyltransferase did not. Correction of binding for membrane protein development did not eliminate any of the major differences in developmental patterns between the two markers. These results suggest that development of the choline transporter binding site is regulated independently of the outgrowth of the bulk of cholinergic nerve terminals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431770 TI - Naloxone stimulates comparable release of luteinizing hormone-releasing hormone from tissue fragments from ovariectomized, estrogen-treated young and middle-aged female rats. AB - Endogenous opioids play a role in the regulation of LH-RH neurosecretion throughout the estrous cycle and during the preovulatory LH surge on proestrus. Experimental evidence suggests that opioid influence may be altered with age, and it has been hypothesized that these alterations may contribute to the loss of regular estrous cyclicity in aging female rats. The present study utilizes an in vitro perifusion paradigm to compare the ability of opiate receptor blockade with naloxone to stimulate LH-RH release from tissue fragments from ovariectomized, estrogen-treated young and middle-aged females. Naloxone stimulated a greater than 50% increase in LH-RH release from most fragments that contained primarily LH-RH axons and terminals and from all tissue fragments that contained the majority of LH-RH cell bodies as well as axons and terminals. The LH-RH response to naloxone administration was qualitatively, quantitatively and temporally comparable in tissue fragments from young and middle-aged animals. These data suggest that LH-RH neurosecretion in ovx, estrogen-primed middle-aged female rats remains under the inhibitory influence of endogenous opioid peptides. Although in vitro LH-RH release did not differ in response to naloxone, age-related differences in naloxone's ability to increase serum LH levels in vivo were observed. The data are discussed with regard to potential age-related differences in pituitary responsiveness to LH-RH and in other systems that enhance pituitary responsiveness to LH-RH as well as alterations in excitatory or inhibitory influences that may have been eliminated in the in vitro protocol. PMID- 8431771 TI - Responses of neurons in the rostral ventrolateral medulla of the cat to natural vestibular stimulation. AB - To investigate the neural substrate of vestibulo-sympathetic reflexes, we studied the responses of neurons in the rostral ventrolateral medulla (RVLM) of decerebrate cats to natural stimulation of the labyrinth in vertical and horizontal planes. The RVLM is a major source of excitatory inputs to sympathetic preganglionic neurons. The animals used in these studies were baroreceptor denervated and vagotomized and had a cervical spinal transection so that inputs from tilt-sensitive receptors outside of the labyrinth did not influence the units we recorded. Of the 38 neurons whose type of vertical vestibular inputs could be classified, the majority (27) received signals mainly from otolith organs. Only 4 of the neurons received inputs predominantly from vertical semicircular canals, and 7 were classified as having convergent inputs from otoliths and canals that were spatially aligned (2 cells) or misaligned (5 cells). In addition, only 2 of 68 neurons tested responded to sinusoidal horizontal rotations in a manner typical of brainstem neurons that receive inputs from the horizontal semicircular canals. Thus, the vestibular inputs to the RVLM appear to come mainly from otolith receptors. In labyrinthectomized cats, we were unable to locate neurons with responses to tilt similar to those of cells recorded in labyrinth-intact cats, confirming that the responses attributed to vertical vestibular inputs were produced by signals from the labyrinth. In animals whose semicircular canals had been rendered dysfunctional by plugging, we only recorded responses similar to those of neurons classified as having mainly otolith inputs in canal-intact animals, indicating that the dynamic behavior of these cells does not depend upon canal inputs. The presence of otolith inputs to the RVLM is consistent with the hypothesis that this region mediates vestibulo sympathetic reflexes involved in correcting posturally-related changes in blood pressure. PMID- 8431772 TI - Long-term potentiation in rat piriform cortex following discrimination learning. AB - The behavioral conditions for induction of long-term potentiation (LTP) elicited by unilateral patterned electrical stimulation of the lateral olfactory tract (LOT) was studied in piriform cortex. A group of animals was trained to discriminate two natural odors while another group was trained to discriminate a patterned stimulation (bursts of 4 pulses at 100 Hz repeated at 160-ms intervals) used as an olfactory cue, versus a natural odor. Both groups were successful in the discrimination and no statistical significant difference was observed in behavioral data between these two groups on series of 5 successive daily training sessions. With animals trained to perform the task with the artificial cue, monosynaptic responses evoked by single pulse stimulation of the LOT were collected, prior to and just after each of the successive training sessions. Comparisons with behavioral data collected at the beginning and the end of a training session revealed that the population synaptic responses increased with the percentage of correct responses performed by the animals. This increase (LTP) was progressive and present only when significant discrimination between the two cues was observed. A positive correlation was found between the increase in monosynaptic responses and the level of performance. Responses elicited by control electrodes were slightly depressed at the end of the discrimination learning series. In addition, when a group of naive animals was pseudoconditioned, giving the patterned electrical stimulation for the same number of sessions but without any olfactory training, no LTP was recorded.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431773 TI - Induction of brain cytochrome P-450IIE1 by chronic ethanol treatment. AB - Cytochrome P-450 mediated metabolism is potentially involved in the expression of the pharmacological and/or toxicological effects of a wide variety of drugs and environmental chemicals upon tissues which contain this metabolic system. In the present investigation, the presence of cytochrome P-450IIE1 and associated mono oxygenase activities in brain and the effect of chronic ethanol treatment on brain cytochrome P-450 (P-450) were studied. Aniline hydroxylase, N-nitroso dimethylamine N-demethylase and p-nitrophenol hydroxylase activities (known to be mediated by P-450IIE1) were detectable in brain microsomes from untreated rats and were about 5%, 125% and 8.3%, respectively, of the corresponding hepatic levels. Chronic ethanol treatment resulted in induction of the above enzyme activities in brain microsomes by 243%, 496% and 155%, respectively. Intake of ethanol for a prolonged period also resulted in the induction of total P-450 in the brain (150% of the control). Addition of the antisera raised against rat liver cytochrome P-450IIE1 markedly inhibited brain microsomal p-nitrophenol hydroxylase activity. Immunoblot analysis of rat brain microsomes using the above antisera also revealed the induction of brain cytochrome P-450IIE1 following chronic ethanol administration. Immunocytochemical localization of cytochrome P 450IIE1 using the above antisera, revealed the preferential localization of the enzyme in the neuronal cell bodies in the cortex, hippocampus, basal ganglia, hypothalamic nuclei and reticular nuclei in the brainstem of rats treated chronically with ethanol. Based upon these studies, it is conceivable that chronic alcohol ingestion could enhance the sensitivity of certain regions of the brain to environmental chemicals that are metabolized to more toxic derivatives by the P-450 system. PMID- 8431774 TI - Tail-pinch induced analgesia and immobility: altered responses to noxious tail pinch by prior pinch of the neck. AB - Noxious pinch to the scruff of the neck using a metal clip produces profound immobility and analgesia. Noxious pinch delivered to the tail fails to induce immobility and results in nociceptive behavior directed at the pinched tail. However, when administered shortly after neck-clip removal, noxious tail-pinch reinstated immobility without any nociceptive response. Prior neck-clip also enhanced the antinociception induced by the tail-pinch as measured by nociceptive response to a leg pinch. Immobility, as well as antinociception, decreased as the time interval between neck-clip removal and the tail-pinch application increased. Pharmacological manipulations which reduce nociception produced a similar alteration in the response to tail-pinch. Thus, following local injections antinociceptive doses of lidocaine to the base of the tail and systemic morphine administration tail-pinch produced marked immobility. Transection of the brain at the intercollicular level provides evidence for supraspinal involvement in post neck pinch effects. Not only was the ability of prior neck-pinch to confer antinociceptive properties on tail-pinch abolished, but increased responsiveness to noxious tail-pinch was seen. We, therefore, propose that prior neck-pinch confers new stimulus properties on noxious pinch of other body regions resulting in an enhanced antinociceptive effect, which affects both remote regions and the site of stimulation, and the ability to induce immobility. PMID- 8431775 TI - Corticotropin-releasing factor enhances noradrenaline release in the rat hypothalamus assessed by intracerebral microdialysis. AB - Corticotropin-releasing factor (CRF) at a dose of 3 micrograms administered intracerebroventricularly (i.c.v.) elicited increases in noradrenaline (NA) release, which was assessed by intracerebral microdialysis in the anterior hypothalamus of conscious rats. These increases persisted until 140 min after infusion of CRF. These results indicate that CRF enhances NA release in the hypothalamus, an effect which may underlie the 'stress-like' properties of CRF. PMID- 8431776 TI - Autoradiographic analyses of the effects of estradiol benzoate on [3H]paroxetine binding in the cerebral cortex and dorsal hippocampus of gonadectomized male and female rats. AB - Effects of estradiol benzoate (EB) on [3H]paroxetine binding in dorsal hippocampus and cerebral cortex of gonadectomized male and female rats were evaluated by quantitative autoradiography. EB significantly decreased [3H]paroxetine binding in male and female rats in the oriens layers of CA1-CA4, and in the radiata/lacunosum moleculare layers of CA2 and CA3. Sex differences were also noted, with binding of [3H]paroxetine being significantly lower in female rats in the radiata/lacunosum moleculare layers of CA2 and CA4, and in the suprapyramidal dentate. No significant effects of either EB or sex were noted in the cortex. PMID- 8431777 TI - Melatonin synthesis and circadian tryptophan hydroxylase activity in chicken retina following destruction of serotonin immunoreactive amacrine and bipolar cells by kainic acid. AB - The neurotoxic excitatory amino acid analog, kainic acid, was used to destroy serotonin-immunoreactive inner retinal neurons, bipolar cells and amacrine cells, in retinas of chickens. Tryptophan hydroxylase activity and melatonin content were examined in the kainic acid-lesioned retinas. Tryptophan hydroxylase activity was present in kainic acid-lesioned retinas and displayed a circadian rhythm. Nocturnal levels of activity in lesioned and control retinas were similar. Melatonin synthesis occurred in kainic acid-lesioned retinas in a diurnal cycle as in normal retinas. Dark-phase melatonin content of kainic acid lesioned retinas exceeded that of controls. We conclude that most, if not all, circadian tryptophan hydroxylase activity and melatonin synthesis occurs in cells other than the cells that contain most of the serotonin in retina, serotonin immunoreactive bipolar and amacrine cells. PMID- 8431778 TI - Diencephalic projections to the retinae in two species of flatfishes (Scophthalmus maximus and Pleuronectes platessa). PMID- 8431779 TI - The neurotoxicity of sulfur-containing amino acids in energy-deprived rat hippocampal slices. AB - The rat hippocampal slice preparation and its electrophysiology were used to assess the toxicity of two sulfur-containing amino acids, L-cysteate (CA) and L cysteine (CYS). Both compounds were innocuous under normal conditions but became toxic in energy-deprived (lack of oxygen or glucose) slices. CA and CYS toxicity was apparent as both reduced the number of slices that normally recover their neuronal function (evoked CA1 population spike) after a standardized period of hypoxia or glucose deprivation (GD). The competitive N-methyl-D-aspartate (NMDA) antagonist DL-2-amino-5-phosphonovalerate blocked the toxicity of both CA and CYS in hypoxic slices, but it was effective only against CYS toxicity in glucose deprived slices. The glycine antagonist 7-chlorokynurenate blocked CA and CYS toxicity in hypoxic slices but was unable to block their toxicity in glucose deprived tissue. Perfusing slices with medium containing a high magnesium concentration blocked the toxicity of CA in both hypoxic and glucose-deprived slices, a treatment that was ineffective against CYS toxicity under either condition. Calcium depletion from the perfusion medium completely blocked the damaging effect of both amino acids in hypoxic slices, but it only partially blocked the toxicity of CA and did not block that of CYS in glucose-deprived slices. These results suggest that CA and CYS activate different NMDA receptor subsets and other glutamate receptor subtypes. Moreover, the results indicate a possible difference between the mechanism that lead to hypoxic neuronal damage and the one that lead to hypoglycemic neuronal damage. PMID- 8431780 TI - Effect of amplitude-modulated radio frequency radiation on cholinergic system of developing rats. AB - We examined the effect of long-term exposure to radio frequency radiation 147 MHz and its sub-harmonics 73.5 and 36.75 MHz amplitude modulated at 16 and 76 Hz (30 35 days, 3 h per day) on cholinergic systems in developing rat brain. A significant decrease in acetylcholine esterase activity was found in exposed rats as compared to the control. Decrease in acetylcholine esterase (AChE) activity was independent of carrier wave frequencies. A short-term exposure did not have any significant effect on AChE activity. PMID- 8431781 TI - Detection and measurement of an endogenous clonidine-displacing substance in human cerebrospinal fluid. AB - Clonidine-displacing substance (CDS) is a novel endogenous ligand for clonidine receptors previously detected in bovine brain and human serum. We examined for the first time whether CDS can be detected and measured in human cerebrospinal fluid (CSF). Using the [3H]clonidine displacement assay, we found that CDS could be identified and quantified in each of the CSF samples obtained from 81 patients with various neurological disorders. Mean level of CDS in CSF was 4.66 units/ml. Exceedingly high levels were observed in the CSF of patients with neoplastic meningitis (mean, 36.75 units/ml) and stroke (mean, 19.5 units/ml) (P < 0.0001). No correlation was found between CDS levels in CSF and age, gender, CSF protein or number of cells. CDS levels in CSF were higher than those in the serum (P < 0.01). We conclude that CDS is present and can be measured in human CSF. High CDS levels in CSF from patients with leptomeningeal metastases may serve as a tumor marker for malignant infiltration of the meninges. Additional studies in stroke patients will determine whether this endogenous ligand plays a role in the pathogenesis of cerebral ischemia. PMID- 8431782 TI - Nerve growth factor increases cortical choline acetyltransferase-positive fiber staining without affecting cortical cholinergic neurons. AB - Lesions of the nucleus basalis magnocellularis (NBM) increased the number of neurons in the frontal neocortex staining for choline acetyltransferase (ChAT). Intracerebroventricular treatment with nerve growth factor (NGF; 10 micrograms per day for 6 weeks) did not further increase this number. NGF increased the size of NBM neurons [Brain Res., 584 (1992) 55-63], but not those in the neocortex. However, NGF increased the area of ChAT-positive fiber staining in the neocortex. These data suggest that NGF enhances cholinergic innervation to the neocortex by affecting residual NBM neurons, rather than cortical cholinergic neurons. PMID- 8431783 TI - Repeated stressful experiences differently affect the time-dependent responses of the mesolimbic dopamine system to the stressor. AB - The increase in mesolimbic dopamine (DA) release observed during the first 40 min of 120 min restraint in naive rats is not evident in repeatedly stressed animals (daily 60 min restraint, for 5 days). However, repeatedly stressed rats show a significant decrease in DA release from 80 min of restraint onwards which is not observable in naive rats. These results indicate that repeated stressful experiences do not produce habituation but alter the response of mesolimbic DA system to the stressor. Moreover, they point to a possible neuronal mechanism underlying stress-induced depression. PMID- 8431784 TI - Gender- and handedness-related differences of forebrain oxygenation and hemodynamics. AB - To elucidate gender- and handedness-related differences between the hemispheres of the brain in their metabolisms and hemodynamics, simultaneous monitoring by near-infrared (NIR) spectrophotometry of hemoglobin (Hb) in both hemispheres of the forebrain during the mirror drawing task (MDT) was performed. Bilaterally simultaneous increases of oxygenated Hb and decreases of deoxygenated Hb in forebrain occurred symmetrically in all cases of volunteer subjects except for two. There were gender- and handedness-related differences of hemodynamics between the hemispheres of the brain; NIR results showed that a large majority of women used both sides of the brain when concentrating on carrying out the MDT, whilst most men, especially left-handers, reacted mainly using the hemisphere which was 'dominant' according to handedness. PMID- 8431785 TI - Sprouting of peripheral nerve axons in the spinal cord of monkeys. AB - It has been previously suggested that two conditions must be met in order for sprouting to occur in the dorsal horn of the spinal cord: afferent fibers must be stimulated to grow and alternate synaptic sites must be made available. We show that reversibly deactivating peripheral nerve axons by nerve crush alone, which produces little or no additional available synaptic sites, results in expansion of the peripheral nerve inputs in the spinal cord in both adult and infant macaque monkeys. PMID- 8431786 TI - Alterations of serotonin receptor binding in the hypothalamus following acute denervation. AB - Quantitative autoradiography was used to determine the effect of acute serotonergic denervation with 5,7-dihydroxytryptamine (5,7-DHT) or serotonin 5HT1a and 5-HT1b receptors in male rats. Seven days after intrahypothalamic 5,7 DHT injection there was a significant increase in the density of 5HT1a receptors in the ventromedial and dorsomedial hypothalamic nuclei (VMN and DMN) of male rats. In adjacent sections. 5-HT1b receptors were significantly increased only in the VMN. No changes in receptor density were observed in the lateral hypothalamic area or hippocampus even though binding of [3H]paroxetine, which labels the presynaptic transporter site, was significantly decreased in all evaluated brain regions in 5,7-DHT-treated animals. In addition to demonstrating that 5-HT1a and 5-HT1b receptors are differentially regulated in different brain areas, these results show that in the brain regions examined both 5-HT1a and 5-HT1b receptors are primarily post-synaptic. PMID- 8431787 TI - Climbing fiber representation of the renal afferent nerve in the vermal cortex of the cat cerebellum. AB - In order to understand how the cerebellum may participate in various autonomic functions, it is necessary to first determine the occurrence and distribution of the various visceral inputs in the cerebellar cortex and their relation to other cerebellar afferents. This study examines the organization of climbing fiber responses (complex spikes) of Purkinje cells elicited by electrical stimulation of the renal afferent nerve and their relationship to climbing fiber responses representing the body surface. Visceral and somatic afferent responses were mapped in the lateral vermal cortex of lobules V to VII in chloralose anesthetized cats. Extracellular single-unit recordings were made from 628 Purkinje cells, of which 14% had climbing fiber responses induced by renal afferent nerve stimulation. Except for one Purkinje cell, the renal climbing fiber input converged with somatic induced climbing fiber input. Tactile stimulation also elicited 54% of cells, which were unresponsive to the renal afferent nerve stimulation. The occurrence and distribution of the climbing fiber responses elicited by renal afferent nerve stimulation varied between lobules V, VI, and VII for the proportion of responsive units, the onset latencies, and topological organization. More renal responsive units were encountered in lobules V (18%) and VII (17%) than in lobule VI (6%), the average latency of renal climbing fiber responses was significantly longer in lobule VII than in lobules V and VI, and the latencies were also different among various parasagittal planes in lobules V and VII. The proportional representation of various body areas for cells with renal and somatic convergent input was different than for cells with only somatic representation. Proportionally, the forelimb had the greatest representation in lobule V, split receptive fields were frequently represented in lobule VI, and the face was well represented in lobule VII. The results of this study, in conjunction with studies showing climbing fiber representation of the vagal and splanchnic nerves, further substantiate role of the cerebellum in autonomic functions. PMID- 8431788 TI - Local cerebral glucose utilization in the interictal state of the spontaneously epileptic rat (SER). AB - Local cerebral glucose utilization (LCGU) in spontaneously epileptic rats (SER) and in their parent strains, zitter (ZI) and Kyoto-Wistar (KW) rats was studied by autoradiography with [14C]2-deoxyglucose. Compared to the LCGU in age-matched KW rats, LCGU in 8-week-old SERs, which had not yet exhibited epileptic seizures, was low in all brain regions examined, and there were no significant differences among the regions. Moreover, there were no differences in LCGU among all regions examined in both SERs and in ZI rats. By contrast, the interictal LCGU in 13-week old SERs, which did exhibit epileptic seizures, was generally lower than in the other two strains, particularly in the hippocampus and amygdala. These findings suggest that the epileptogenic focus in SERs may lie in the hippocampus and amygdala. PMID- 8431789 TI - Synthetic Alzheimer amyloid beta/A4 peptides enhance production of complement C3 component by cultured microglial cells. AB - Primary microglial cultures prepared from newborn mice showed the production and release of the third component of complement (C3). Newly synthesized [35S]methionine-labelled C3 was purified by immunoprecipitation using anti-C3 antibody. C3 was detected by SDS-PAGE and fluoroaraphy of the immunoprecipitated protein from cell lysates as a 195 kDa band, and from the supernatants of cultures as two major bands corresponding to the C3 alpha-chain (125 kDa) and beta-chain (75 kDa), consistent with known C3 characteristics. Increased biosynthesis of C3 was elicited by endotoxin lipopolysaccharide (LPS). Further, the synthesis of C3 was increased 5-10-fold in response to various synthetic peptides corresponding to the amyloid beta/A4 protein, which is the main constituent of extracellular amyloid deposits in Alzheimer's disease (AD). The increased synthesis of C3 was shown to be dose dependent at concentrations of beta/A4 peptide ranging from 10 micrograms/ml to 50 micrograms/ml. These results suggest that complement components found previously in amyloid deposits may be partly derived from reactive microglia preferentially associated with senile plaques in AD brain. PMID- 8431790 TI - Review of thrombolytic use in acute myocardial infarction, pulmonary embolism, and cerebral thrombosis. PMID- 8431791 TI - Transplantation: a review of immunosuppressive agents. PMID- 8431792 TI - Current trends in antimicrobial therapy for the critically ill patient. PMID- 8431793 TI - Trends in agents used for the management of sepsis. PMID- 8431794 TI - The anesthetic management of the trauma patient. PMID- 8431795 TI - Neuromuscular blockade: nursing interventions and case studies from infancy to adulthood. PMID- 8431796 TI - The role of analgesics and sedatives in the management of pain and agitation during weaning from mechanical ventilation. PMID- 8431797 TI - Pharmacologic management of cerebral vasospasm. PMID- 8431798 TI - Immunomodulating effects of intestinal absorbed maternal colostral leukocytes by neonatal pigs. AB - Intestinal absorption of fluorescein isothiocyanate-labelled maternal colostral leukocytes (FITC-CL) was studied in 49 neonatal colostrum-deprived (CD) pigs from nine Minnesota miniature sows. Within 2 h postfeeding (pf), maternal FITC-CL were absorbed from the sibling's digestive tract and migrated into blood. The peak appearance of FITC-CL in blood occurred in samples at 5 and 7 h pf. By 24 h pf, cells were detected in liver, lung, lymph nodes, spleen and gastrointestinal tissues. To confirm intercellular migration of FITC-CL, gastrointestinal explant cultures from neonatal CD pigs were used. Maternal FITC-CL were observed to intercellularly migrate in 24 to 48 h pf between duodenal- and jejunal-epithelial cells to lamina propria cells and submucosal spaces. Fluorescein isothiocyanate labelled maternal colostral leukocytes were not absorbed via ileal explant cultures. Unlike FITC-CL, maternal FITC-peripheral blood mononuclear leukocytes (FITC-PBL) were not absorbed either in vivo or in vitro by gastrointestinal tissues. When maternal FITC-PBL were intravenously administered to siblings they were distributed in blood and organs similar to FITC-CL. Following exposure to FITC-labelled cells, treated- and mock (untreated)-pigs were compared on the basis of PBL proliferative responses to phytomitogens. Sibling CD-pigs fed maternal FITC-CL showed higher PBL T-cell responses to phytohemagglutinin (PHA) and concanavalin A (ConA), and a significant stimulation (p < or = 0.01) of B cell responses to pokeweed mitogen (PWM). Pigs fed FITC-PBL showed little PBL responses to PHA, ConA and PWM over PBL from mock pigs. Similarly, the influence of noncellular constituents of colostrum were also assessed by proliferative studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431799 TI - The influence of the swine major histocompatibility genes on antibody and cell mediated immune responses to immunization with an aromatic-dependent mutant of Salmonella typhimurium. AB - Eighty-two major histocompatibility complex (MHC) swine leukocyte antigen (SLA) defined miniature pigs from 16 litters were examined for serum agglutinating antibody titer and O-polysaccharide (O-ps) specific peripheral blood lymphocyte blastogenesis following two parenteral vaccinations with 1 x 10(8) aromatic dependent (aroA) Salmonella typhimurium and following oral challenge with 1 x 10(12) virulent parent S. typhimurium. Least mean squares analysis allowed separate determinations of the effects of MHC genotype, dam, sire and litter. In most cases only litter significantly influenced both lymphocyte blastogenesis and antibody titer before and after vaccination and following challenge. However, pig SLA haplotype significantly influenced the degree of O-ps specific lymphocyte proliferation six days after the second vaccination (p < 0.004). Lymphocyte proliferation and serum agglutinating antibody response six days after primary vaccination were negatively correlated (r2 = -0.68, p < 0.001). In most cases, "dd" and "gg" homozygous and "dg" heterozygous pigs, having the same MHC class II region, behaved immunologically as a group distinct from the other genotypes. PMID- 8431800 TI - A sandwich enzyme-linked immunosorbent assay for the detection of Streptococcus suis. AB - A double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) was developed for the detection and the identification of Streptococcus suis capsular types 1, 2, 1/2, 3 and 22. The specificity of this test was first evaluated using reference strains of S. suis capsular types 1 to 28 and 1/2 as well as 15 different bacterial species susceptible to be isolated from swine. The ELISA developed was very specific for capsular types 1, 3 and 22 but it could not discriminate between capsular types 2 and 1/2. In a second study, S. suis isolates from 328, 493, 368 and 76 diseased pigs were used to detect capsular types 1, 2 or 1/2, 3 and 22 respectively. The relative specificity and sensitivity varied between 98% and 100%. The ELISA results were in excellent agreement with the standard techniques (biochemical tests, coagglutination and capsular reaction tests) in detecting both positive and negative strains. Kappa values were 0.80, 0.99, 0.97 and 1.00 for detecting S. suis capsular types 1, 2 or 1/2, 3, and 22 respectively. To evaluate the relative-sensitivity of the test, primary cultures from 73 diseased pigs and tissue samples from 67 diseased pigs were used directly for detecting these capsular types. With primary cultures, the relative specificity and sensitivity (95.9% and 91.6% respectively) remained high and the test was very suitable (Kappa = 0.87). The ELISA using tissue samples gave a good specificity (97.6%), a moderate sensitivity (62.5%) and a low agreement with standard tests (Kappa = 0.64).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431801 TI - Abnormal modelling of trabecular bone in calves. AB - Lesions due to abnormal modelling of trabecular bone were identified in the femurs of 26 of 55 prenatal and neonatal calves at postmortem examination. Abnormalities included growth retardation lines and lattices, focal retention of primary spongiosa and persistence of secondary spongiosa. The possible cause and pathogenesis of these lesions is discussed. The normal radiographic and histological appearance of the developing bovine femur, during the last four months of gestation, is also described. PMID- 8431802 TI - Evaluation of rapid gross visual appraisal of swine lungs at slaughter as a diagnostic screen for enzootic pneumonia. AB - A rapid gross visual appraisal of enzootic pneumonia lesions was made of 87 lungs at a local abattoir and the lungs were then set aside and examined in more detail. A sample of pulmonary tissue was taken from each lung and submitted for bacterial and histological examination. The principal investigator who had performed the gross and detailed lung scores was then used to assess the agreement of two inspectors who were scoring lung lesions in the abattoir. The Pearson's correlation coefficient between grossly scored lungs and scores derived from a detailed examination was 0.94. Using histological examination as the gold standard, rapid gross examination had a sensitivity of 76% and a specificity of 71%. Using bacterial recovery as a gold standard yielded a sensitivity of 77% and a specificity of 51%. The sensitivity and specificity of inspectors 1 and 2 compared to the principal investigator were: sensitivity = 97.5% and specificity = 97.4% for inspector 1, and 97% and 98% for inspector 2. The kappa values for both of the inspectors compared to the principal investigator were 0.95 suggesting that designated lay inspectors consistently agreed with the principal investigator. PMID- 8431803 TI - The effect of exploratory laparotomy on the serum and peritoneal haptoglobin concentrations of the pony. AB - Serum haptoglobin concentration was used as an indicator of the acute phase response in ponies undergoing exploratory laparotomy. Preoperative, 1 h intraoperative, 3 h, 6 h, 12 h and 24 h postoperative blood samples and 48 h postoperative peritoneal fluid samples were obtained for haptoglobin analysis. A spectrophotometric assay based on cyanmethemoglobin binding capacity (CyanBC) was used to determine haptoglobin concentrations. The preoperative reference range for serum haptoglobin concentrations in these ponies was 25-60 mg CyanBC/dL. Intraoperative and 3 h postoperative blood samples had decreased haptoglobin concentrations when compared to preoperative values. Serum haptoglobin concentrations began to rise by the 6 h postoperative sample and were generally elevated above preoperative values by the 24 h postoperative sample. Two of the ten ponies had mild signs of postoperative colic which were associated with twofold elevations in serum haptoglobin concentrations and fivefold elevations in peritoneal fluid haptoglobin concentrations. PMID- 8431804 TI - Sensitive and specific polymerase chain reaction detection of Toxoplasma gondii for veterinary and medical diagnosis. AB - A polymerase chain reaction (PCR) method was developed for the detection of Toxoplasma gondii. A universal- and a T. gondii-specific primer was used to amplify a region of the small subunit ribosomal RNA gene. This approach allows for a theoretical detection limit of 0.01 zoite of T. gondii per sample assayed. Experiments showed that this PCR method could detect 0.1 pg of T. gondii DNA, which represents about one organism. Polymerase chain reaction tests using DNAs of cat, dog, swine, cattle, human, Sarcocystis cruzi, Eimeria ahsata, E. vermiformis, and Escherichia coli indicated no cross-reaction with nucleic acids of hosts, related coccidia, or bacteria. Data on the sensitivity and specificity suggest that this PCR assay could be extremely useful for the diagnosis of toxoplasmosis in human and veterinary medicine, as well as for food safety surveys. PMID- 8431805 TI - Production of capsular material by Streptococcus suis serotype 2 under different growth conditions. AB - The procedure currently used for the production of Streptococcus suis antigen is very long and includes several subcultures. The aim of the present work was to study the in vitro production of capsular material by S. suis serotype 2 after each of these subcultures. The amount of capsular material produced was evaluated by electron microscopy using bacterial cells grown on blood-agar plates and in Todd-Hewitt broth (THB) or THB supplemented with serum. In addition, the production of antibodies in rabbits with antigens produced using different growth conditions was compared. Antigens produced after only three subcultures possessed as much capsular material as cells obtained after the complete procedure and induced a similar antibody response. The use of serum as a supplement to the broth did not assure a higher production of capsule; in addition, antibody titers obtained with antigens produced in THB were as high as those obtained with antigens produced in THB supplemented with serum. We recommend the use of three subcultures in nonsupplemented broth for the production of immunogens. This revised protocol offers two main advantages: it is less time-consuming because of the limited number of subcultures and is also less expensive since nonsupplemented broths are used. PMID- 8431806 TI - Alterations of fluid and electrolyte balance in thoroughbred racehorses following strenuous exercise during training. AB - Alterations of acid-base status, and fluid and electrolyte balance subsequent to exercise in Thoroughbred racehorses in North America have not been well characterized. Des-cribed here are the results of an observational study conducted to characterize changes in fluid and electrolytes following strenuous exercise of 16 Thoroughbreds under routine training conditions. Changes following strenuous exercise were determined for the following variables: serum concentrations of sodium (Na), potassium (K), chloride (Cl) and protein; pH of blood; osmolality of plasma and urine; body weight; and, fractional urinary excretion (FE) of Na, K and Cl. The following changes occurred during exercise: increased concentration of Na in blood; increased FE of Na; decreased concentration of Cl in blood; decreased FE of Cl; increased urinary and plasmal osmolality; weight-loss; decreased pH of blood; and, increased concentration of lactic acid. The concurrent decreased concentration of chloride in plasma and acidemia in these horses differed from the hypochloremic, metabolic alkalosis previously described among endurance horses. Acidemia was attributed to production of lactic acid by anaerobic glycolysis. PMID- 8431807 TI - Physicians and the pharmaceutical industry. PMID- 8431808 TI - Physicians and the pharmaceutical industry. PMID- 8431809 TI - Confidentiality and research. PMID- 8431810 TI - Patients' right to records. PMID- 8431811 TI - Nasogastric tube placement. PMID- 8431812 TI - Clinical practice guidelines for treatment of diabetes mellitus. PMID- 8431813 TI - Understanding the transition from head nurse to nurse manager. PMID- 8431814 TI - Initiating, conducting and maintaining guidelines development programs. PMID- 8431815 TI - Periodic health examination, 1993 update: 2. Lowering the blood total cholesterol level to prevent coronary heart disease. Canadian Task Force on the Periodic Health Examination. PMID- 8431816 TI - Evaluation of inactivated hepatitis A vaccine in Canadians 40 years of age or more. AB - OBJECTIVE: To assess the side effects and immune responses after three serial doses of a new inactivated hepatitis A vaccine in people 40 years of age or more. DESIGN: Open, noncomparative trial. SETTING: A hospital, a regional laboratory and public health units in British Columbia. PARTICIPANTS: A volunteer sample of 64 healthy adults aged 40 to 61 years who were seronegative for hepatitis A virus (HAV). All were staff or associates of the health facilities. Exclusion criteria included elevated serum alanine and aspartate aminotransferase levels, a history of liver disease and recent travel to areas of high risk for HAV infection. INTERVENTION: A formalin-inactivated, alum-adsorbed vaccine containing 720 ELISA (enzyme-linked immunosorbent assay) units of antigen from HAV strain HM175 per 1.0-mL dose was injected intramuscularly into the delgoid area. The second and third doses were given 1 and 6 months later respectively. MAIN OUTCOME MEASURES: A detailed diary of any adverse effects for 3 days after each dose. HAV antibody levels in blood samples taken before and 30 days after each dose. RESULTS: All subjects completed the planned series of vaccinations and blood tests; symptom diaries were returned after 190 (99%) of 192 vaccinations. Local symptoms, most often soreness, were reported after 46% of the vaccinations but were mild and usually resolved within 24 hours. A temperature of more than 38.0 degrees C was never reported. Seroconversion occurred in all cases after the two primary doses, and the subjects were still seropositive at 6 months. After the booster dose the geometric mean titre was 2380 mIU/mL, all values being 200 mIU/mL or greater. CONCLUSION: In healthy adults 40 years of age or more the HAV vaccine was well tolerated and highly immunogenic. Final antibody levels were much higher than reported in people passively immunized against HAV with immune serum globulin. PMID- 8431817 TI - [Interobserver reliability of a portable tympanometer, the MicroTymp]. AB - OBJECTIVE: To determine the interobserver reliability of tympanograms obtained with the MicroTymp, a portable tympanometer. SETTING: Family medicine teaching unit in a tertiary care hospital. PATIENTS: Thirty-three patients who presented to the ear, nose and throat clinic in August 1990 for an ear problem. INTERVENTION: Three residents in family medicine independently attempted to record with the MicroTymp one tympanogram for the 66 ears. We excluded the results for seven ears for which tympanograms could not be obtained. MAIN OUTCOME MEASURE: Using objective criteria, two family physicians and two residents in family medicine independently classified the 177 tympanograms into five categories (normal, possible effusion, possible perforation, possible tympano ossicular dysfunction and unclassifiable). Reliability was estimated by means of the kappa (kappa) coefficient on 161 tympanograms from 59 ears for which the interpretation of the three tympanograms agreed. MAIN RESULTS: The interpretation of the three tympanograms agreed for 34 of the 59 ears (0.58) (kappa = 0.52, 95% confidence limits 0.45 and 0.59). There was no significant difference in interobserver reliability between pairs of observers or between symptomatic and asymptomatic ears. CONCLUSIONS: The interobserver reliability of the MicroTymp is moderate. The tympanograms obtained with the instrument should be interpreted in the context of the clinical findings. PMID- 8431818 TI - Trends in coronary artery bypass grafting in Ontario from 1981 to 1989. AB - OBJECTIVES: To determine the trends in overall and age-specific rates of coronary artery bypass grafting (CABG) in Ontario from 1981 to 1989 and to assess whether relative resource scarcity, as manifested in waiting lists, resulted in obvious age-related or sex-related changes in utilization. DESIGN: Computerized compilation of hospital discharge abstracts from the Hospital Medical Records Institute. All separations for every other year from Apr. 1, 1981, to Mar. 31, 1990, were included. Procedures rather than patients were the unit of analysis (repeat procedures were double-counted if associated with separate hospital admissions). SETTING: Ontario acute care hospitals offering CABG. PATIENTS: People aged 20 years and over who underwent one or more CABG procedures. RESULTS: The overall rate of CABG increased by 31% in the study period, plateauing only between 1983 and 1985. By 1989-90 the rate was 66.03 per 100,000. The highest annual increase in the rate was among people aged 65 to 74 years, at 17.61 procedures per 100,000, as compared with 4.64 per 100,000 among people 75 years and over. In 1989-90 those aged 65 and over represented 37% of the total caseload. The overall male:female ratio did not change significantly throughout the study period. CONCLUSIONS: Since the CABG utilization rate continues to increase in Ontario, recent waiting lists must be due to a disproportionate growth in demand. There was no convincing evidence of age-related or sex-related discrimination in allocating this limited resource. Supply-demand mismatch was driven above all by the continued increase in CABG use among elderly people. PMID- 8431819 TI - Disseminated cutaneous infection due to Mycobacterium tuberculosis in a person with AIDS. PMID- 8431820 TI - Familial defective apolipoprotein B-100: a cause of hypercholesterolemia and early coronary heart disease. PMID- 8431821 TI - Symposium on fats in human nutrition. 1957. PMID- 8431822 TI - Insects and entomologists become police tools in murder investigations. Interview by Anne Tempelman-Kluit. PMID- 8431823 TI - HIV and Canada's hemophiliacs: looking back at a tragedy. PMID- 8431824 TI - Menopause comes out of the closet. PMID- 8431825 TI - "Smart-drug, smart-food" fad winning converts despite scientists' scepticism. PMID- 8431826 TI - US resistance to Canadian mammogram study not only about data. PMID- 8431827 TI - Too many specialists, not enough GPs: Poland seeks change in wake of East Bloc collapse. PMID- 8431828 TI - Supreme Court decision may have major impact on drug industry. PMID- 8431829 TI - When science and passion meet: the impact of AIDS on research. PMID- 8431830 TI - Who are the elderly? A profile of older patients. AB - The graying of America will change the health care system and how health professionals view the quality of care and life for older citizens. In this article, the demographics of US society are explored with comments on forecasted changes in the next 30 years. Understanding the needs of the geriatric population will help the clinician provide an opportunity to plan for the future to ensure a meaningful life for those golden years. PMID- 8431831 TI - Heel pain in the older patient. AB - Older Americans are the fastest growing segment of the US population. For this group, mobility is a significant factor in individual well-being. Heel pain is primarily a symptom found in adults, and like most health problems, increased age has a compounding effect on most disease processes. If heel pain becomes the cause of immobility in an older patient, significant consequences may arise. The true prevalence of heel pain in older individuals is not known precisely. The frequency may lie between 12.5% and 15% on the basis of reports in the literature. The scientific basis of these figures, however, is open to question. No one method of organizing heel pain according to a causative agent or condition is accepted universally. A review of the literature, however, reveals that most reporters ultimately include the same elements in whatever schema they use. In general terms, management of heel pain, regardless of the cause, can be organized according to noninvasive to invasive treatment methods. The authors have found the categories of mechanical, pharmacologic, and surgical to be useful. Selection of a therapeutic method is based on the patient's specific physical circumstance and social situation. PMID- 8431832 TI - Nonsurgical management of disorders of the forefoot. AB - This article reviews some of the conservative methods used by many podiatric physicians to manage common forefoot pathologic conditions identified in the geriatric population. It is essential that the podiatric physician take an accurate history and perform a comprehensive physical to determine the exact nature of the pathologic condition. Treatment should be directed at the causative factor(s) and be realistic, with all treatment having concern for the patient's well-being. Reasonable treatment goals must be established for the individual, with the ultimate goal being maintenance of ambulatory status. PMID- 8431833 TI - Podiatric surgical considerations in the older patient. AB - The goal of podiatric surgery in the older patient should be pain management with the highest degree of functional restoration. Thorough preoperative analysis, meticulous surgical technique, and careful postoperative planning are necessary to ensure a favorable surgical result. Each planned procedure must coincide with the specific needs of the individual patient while conforming to the body's physical limitations. A complete medical examination with laboratory studies is indicated due to the elderly patient's inherent diminished physical status. When the patient is deemed a proper candidate for surgery, the medical team, family, and friends should be consulted regarding immediate and long-term postoperative care. Strict adherence to these principles is in the best interest of both the practitioner and the older patient. PMID- 8431834 TI - Joint diseases associated with aging. AB - A realistic assessment of the nature, severity, and prognosis of arthritic disorders, appropriate patient education, allaying unrealistic patient fears and minimizing realistic ones, and maintaining the patient's functional independence should be prime considerations in the management of the older patient. Appropriate management of arthritic disorders will alleviate pain, increase functional capacities, and prolong independence. This article considers the diagnosis, presentation, and treatment of specific joint disorders found in the older population, including osteoarthritis, rheumatoid arthritis, gout, and other frequently seen rheumatic disorders. PMID- 8431835 TI - Neurologic manifestations in the lower extremity in elderly persons. AB - According to the US Census Bureau, by the 21st century, approximately 20% of the US population will be over age 65. With the continued emphasis upon primary care, it is imperative that we devise a methodical approach in the assessment of patient problems as well as in the provision of optimal podiatric care in the geriatric community. The distinction between normal physiologic and pathologic neurologic aging processes was discussed in this article from both a diagnostic and prognostic standpoint. Degenerative and neurovascular causative conditions afflicting the lower extremity were discussed in greater detail with regard to clinical, diagnostic, pathologic, therapeutic, and prognostic aspects. It has been the authors' intent to enlighten the readers by providing measures that will secure more timely diagnoses and therapeutic regimens for age-related neuropathologic disorders affecting the foot. PMID- 8431836 TI - General concepts of geriatric medicine. AB - To ensure the maximum quality of life for the elderly, practitioners must be precise in their evaluations. Physiologic aging decreases the reserve of the geriatric patient, making him or her more susceptible to the stress associated with illness, drugs, and surgery. Medications must be prescribed in reduced dosages to compensate for altered pharmacokinetics and pharmacodynamics in the elderly. Musculoskeletal problems, cardiovascular diseases, malignancies, and visual and hearing impairments are seen frequently in this population. Cognitive failure, depression, gait instability and falling, and urinary incontinence may be caused by acute or chronic problems. A comprehensive assessment directed at medical, mental, social, and functional status problems is imperative. PMID- 8431837 TI - Ethical considerations in podiatric care of the older patient. AB - Ethical issues are constantly changing. Today, there is a greater consideration of the social issues as they relate to medical care. The questions of comfort are of greater concern for as we deal with increasing numbers of aging patients and chronic disease, cure may not always be possible; thus, patient management is a key issue. There are greater concerns for the rights of patients, their privacy, and the relationships that need to be maintained between doctors and their patients. There is a greater focus on the quality of life and not just saving a life. There are new questions posed in relation to the termination of treatment, particularly in relation to aging and at what point is there harm and not good from treatment. There is also the issue of public rights and whether the system should be permitted to develop without a freedom of choice or restrictions on podiatric care that are not imposed on any other professional service. Ethics and bioethics in itself is more than a statutory issue, it is more than policy. It also must be an educational issue that considers societal issues in the changing delivery of health care. It must now deal with professional liability and cost containment because now there are mechanisms for the rationing of care based on costs alone. Ethics must be based on respect, obligation, professional responsibility, as well as care issues. It must be an issue of moral relevance. Ethics must continue to deal with conduct, professional relationships, and human dignity. It must deal with improved knowledge and skills. It must consider and maintain the highest possible level of professional judgement. Ethics must also consider professional responsibility and obligation beyond what might be required to meet the legal basis of practice. Simply being "this side of legal" is not adequate in both an ethical and moral sense. If we recognize that it is the public that ultimately will determine our future health care system, partly on a preconceived need, partly on cost, partly on opinion, and partly on political impression, then we in podiatric medicine must assume a greater responsibility in protecting and promoting quality care, ethical conduct, and serving as a moving force in the changes that will take place in our health care delivery system in the future. Foot care is both basic and needed. Our state practice acts and laws and regulations have established this fact and demonstrated a public need for podiatry. Our obligation is to protect that need with integrity. PMID- 8431838 TI - Assessment of the geriatric patient. AB - In its final report, the 1981 White House Conference on Aging recommended that "Comprehensive foot care be provided for the elderly in a manner equal to care provided for other parts of the human body, to permit patients to remain ambulatory: IMPLEMENTATION: Remove current Medicare exclusions which preclude comprehensive foot care." The ability to ambulate requires appropriate foot health as a catalyst. Keeping patients walking is a goal that needs to be met if older persons are to maintain a high degree of quality in their lives. Given the high prevalence of foot problems in elderly persons, especially in those patients with chronic diseases and mental health problems, foot care needs are essential. Foot health, care, and foot health promotion should be part of comprehensive health care for older Americans. The ability to remain active and ambulatory is one means of assuring dignity and self-esteem for the elderly. PMID- 8431839 TI - Onychial disorders in the older patient. AB - Toenail disorders are a common source of discomfort in the older patient. Changes also contribute to potential and significant morbidity when complicated by systemic diseases. Onychodystrophies, infections, the residual of trauma, changes in relation to age, and manifestations of systemic diseases are identified and explored in this article. Key to proper management is the recognition that diseases and disorders of the toenails are not "routine" and that in the older patients they can limit mobility and significantly increase health care costs when complications ensue. PMID- 8431840 TI - Management of hyperkeratotic lesions in the elderly patient. AB - Many factors contribute in the development of hyperkeratotic lesions in the elderly patient. The internal and external causes render the elderly foot more susceptible to limited ambulation, increased incidence of infection, ulceration, and eventual loss of the limb. Once the lesion is classified and the causes identified, a beneficial treatment plan can evolve. Reduction of the lesion(s), appropriate padding, shielding, splinting, accommodative orthoses, insoles, emollients, and mild keratolytics on regular treatment intervals are helpful in maintaining comfort and allowing function of the elderly foot. If the bony abnormalities or abnormal position of the foot do not respond to conservative measures, then surgical intervention should be considered based on the medical and vascular status of the patient. The evaluation of the elderly patient's presenting footwear, and patient education on the need for proper shoe gear size, shape, and materials cannot be overemphasized. Proper footwear and fitting is essential for the elderly in managing hyperkeratotic lesions. When regular footwear is not beneficial special shoes should be considered to accommodate the foot and treatment plan (e.g., accommodative orthoses, and so forth). The Extra Depth Inlay Thermold, Ambulator, Bunion last and Keystone last are options. If special shoes are too heavy for the elderly patient, there is a wide variety of athletic shoes that are shock absorbent and lightweight. Success in management includes a proper identification of the problem, relief of the symptoms, regular follow-up care, and periodic review of footwear to ascertain the need for repair or modification. PMID- 8431841 TI - Age-related changes in elderly individuals. AB - The aging patient has many physiologic and pathologic changes that may require evaluation. The practicing podiatrist should be aware of what is considered normal and what is considered abnormal and be willing to work with the patient to find a health care provider who is willing to address these unique issues. The podiatrist, along with other primary care practitioners, is in a unique position to observe and intervene initially in health care issues that could be life threatening if left untreated. It is important to be alert to these changes and be willing to intervene whenever necessary. PMID- 8431842 TI - Common dermatologic manifestations in the older patient. AB - In the next decade, corporate and medical research funds need to be combined to study geriatric dermatoses a step further. Nutritionally, research on the effect of vitamins and nutrients on the skin is lacking. Geriatric dermatology is fascinating to study because of the multitude of presenting conditions. This article underscores the importance of making a correct diagnosis early in the data-gathering stage of obtaining a patient's history. PMID- 8431843 TI - Radiologic aspects of aging in the foot. AB - This article discusses technical and radiologic aspects that should be considered when evaluating the geriatric population. Potential errors and accidents will be reduced and the office will function more efficiently by advance preparation. The interpreter must be aware of anatomic variations that could potentially be misdiagnosed as a pathologic condition. Finally, the radiographic presentation of disease may differ from that presenting in younger age groups. PMID- 8431844 TI - Preoperative in vitro chemosensitivity test of esophageal cancer with endoscopic specimens. AB - BACKGROUND: From January 1990 to June 1991, the authors tested in vitro chemosensitivity before surgery with endoscopic biopsy specimens from 23 patients with intrathoracic esophageal cancer. METHODS: The authors tested eight anticancer agents using the dye exclusion method, and all 23 patients received chemotherapy with the most sensitive three drugs according to the results of the chemosensitivity test. RESULTS: Ten patients (43.5%) had a tumor reduction of more than 50% on radiologic studies, and 4 patients (17.4%) had a good histologic effect. CONCLUSIONS: The chemosensitivity test is useful in selecting preoperative chemotherapeutic agents for patients with esophageal cancer. PMID- 8431845 TI - MDR1 gene expression and its clinical relevance in primary gastric carcinomas. AB - BACKGROUND: Drug resistance remains a major problem in gastric carcinomas. To evaluate the mechanisms involved in this resistance, the authors determined the expression of the MDR1 gene, a multidrug resistance gene, in primary gastric carcinomas. METHODS: MDR1 RNA levels of gastric carcinoma specimens (n = 22) were determined by slot blot analysis. An MDR1 cDNA (probe 5A) was used for the hybridization. RESULTS: MDR1 RNA was detected in 41% of the gastric carcinomas, with high levels in 18% of the specimens. No expression of the MDR3 gene was observed in these tumors. MDR1 gene expression was independent of patient age, tumor localization, and lymph node involvement. However, MDR1 RNA expression was less frequent in locally advanced tumors and was absent in the primary tumors of all six patients who had distant metastases. CONCLUSIONS: The data indicate that multidrug-resistant cells are present in primary gastric carcinomas and suggest that multidrug resistance might contribute to the clinical drug resistance of these tumors. PMID- 8431846 TI - Multiple polyps of esophagus, stomach, colon, and rectum accompanying rectal cancer in a patient with constitutional chromosomal inversion. AB - BACKGROUND: It has been reported that colorectal carcinomas are caused by a multistage process. In patients with familial adenomatous polyposis, carcinoma of the colorectum frequently develops and occasionally polyps develop in the upper gastrointestinal tract. Chromosomal deletion often is found for chromosomes 5, 17, and 18, on which tumor suppressor genes are located. Furthermore, loss of the alleles of loci on chromosome 3 has been reported in renal cell carcinoma, small cell lung carcinoma, and mixed salivary gland tumor in hereditary and sporadic cases. These data support the concept of a recessive mechanism for the development of human tumors. PATIENTS AND RESULTS: The authors report the case of a 48-year-old woman with rectal cancer accompanied by multiple polyps in the esophagus, stomach, and colorectum. Histologically, the polypoid lesions in the esophagus, stomach, and colorectum showed a thickened mucosa, hyperplastic polyps, and mixed hyperplastic adenomatous polyps, respectively. Karyotype analysis showed 46, xx, inv(3)(p12.2q25.3) in all 20 inspected peripheral lymphocytes. By Southern blot with a c-raf probe, one allele of the c-raf-1 gene, which has been mapped on chromosome 3p25, was deleted from the rearranged chromosome 3 in the peripheral lymphocytes, intact colonic mucosa, and cancer tissue. CONCLUSIONS: These results suggest that the development of hyperplastic polyps and carcinoma of the rectum results from the allelic loss in chromosome 3p, as has been reported for solid tumors at other sites. PMID- 8431847 TI - Extracolonic cancer in hereditary nonpolyposis colorectal cancer. AB - BACKGROUND: It has been hypothesized that in some but not all families with hereditary nonpolyposis colorectal cancer (HNPCC) there is a high risk of certain cancers other than colon cancer. METHODS: The authors compared the observed frequency of cancer at specific sites in more than 1300 high-risk members of 23 kindreds with HNPCC with expectations based on general population incidence and evaluated the hypothesis that there was heterogeneity in cancer frequency among families. RESULTS: The authors observed significantly increased numbers of cancers of the stomach, small intestine, upper urologic tract (renal pelvis and ureter), and ovary. No excess was seen in other cancer types that have been associated previously with HNPCC, including cancer of the breast, pancreas, and urinary bladder. Significant heterogeneity among families was observed in the frequencies of endometrial, ovarian, and upper urologic system cancer. CONCLUSION: In addition to early onset cancers of the colorectum, HNPCC family members are at increased risk for cancers of other gastrointestinal tract organs, and, especially in some families, cancers of the upper urologic and female genital tract. PMID- 8431848 TI - A comparison of flow cytometric and absorption cytometric DNA values as prognostic indicators for pancreatic carcinoma. AB - BACKGROUND: The DNA content of 30 adenocarcinomas of the head of the pancreas was measured by flow and absorption cytometric analysis. METHODS: Each of the patients in this study had curative pancreatoduodenectomy. The absorption cytometric measurements were done in a research laboratory, and the flow cytometric measurements were performed in a commercial laboratory. The DNA measurements were done on nuclei disaggregated from pancreatic cancer tissue blocks without the examiner knowing whether the patient had survived. RESULTS: Twenty-one of the 30 cancers were found to be aneuploid by absorption cytometric analysis, whereas only 1 of the 30 cancers was aneuploid by flow cytometric analysis. This difference was statistically significant (P < 0.001). CONCLUSIONS: Univariate and multivariate analyses showed that the absorption cytometric DNA measurements were stronger prognostic determinants for patient survival than were the flow cytometric DNA measurements, indicating that some caution may be warranted in the interpretation of commercially obtained DNA distributions of pancreatic carcinomas. PMID- 8431849 TI - CA 242 is a new tumor marker for pancreatic cancer. AB - BACKGROUND: The tremendous progress in imaging techniques over the past few years has not resulted in an earlier diagnosis of pancreatic cancer (PC). The search for a noninvasive diagnostic tool, capable of early diagnosis, led to the development of a series of tumor markers. This article discusses the evaluation of the latest one--CA 242--and its comparison with established markers such as CA 19.9, CA 50, and carcinoembryonic antigen (CEA). METHODS: The markers were tested in preoperative serum samples collected from 300 patients and 30 healthy controls between April 1986 and May 1991. There were 68 patients with ductal carcinoma of the pancreas, 24 with other pancreatic tumors, 57 with acute pancreatitis, 29 with chronic pancreatitis (CP), 90 with benign disease of the upper gastrointestinal tract, and 32 with malignant disease. The test for CA 242 consisted of a DELFIA research kit (WALLAC OY, Turku, Finland) with a cutoff level of 20 U/ml. The other markers were tested with commercially available kits. RESULTS: Sensitivities for PC in this population, with other malignant neoplasms accounting for 16% of the group, were 66.2%, 70.6%, and 70.6% for CA 242, CA 19.9, and CA 50, respectively (90% specificity level). The best results were achieved with the combination of CA 242 and CA 50, reaching a sensitivity of 75.0%. The differential diagnosis between PC and CP could be made with a sensitivity of 64.7%, 79.4%, and 77.9%, respectively, for the three markers. CONCLUSIONS: The authors conclude that, on its own, CA 242 does not improve the sensitivities reached with CA 19.9 and CA 50, but the combination does achieve both a higher sensitivity and specificity. PMID- 8431850 TI - Primary T-cell lymphoma of the gastrointestinal tract associated with human T cell lymphotropic virus type I. An analysis using in situ hybridization and polymerase chain reaction. AB - BACKGROUND: During a population-based local cancer registry, a peculiar type of T cell lymphoma restricted to the gastrointestinal tract was found in patients living in southwestern Japan. METHODS: Five cases of gastrointestinal (GI) tract T-cell lymphoma were analyzed with immunohistologic examination, ultrastructural analysis, in situ hybridization (ISH), and polymerase chain reaction (PCR). RESULTS: All cases satisfied the criteria of primary GI tract lymphoma at presentation or operation. Four showed a close relationship to human T-cell lymphotropic virus type I (HTLV-I). Those four had positive results for anti-HTLV I antibody and positive surface markers for CD4, positive hybridization signals by ISH, and HTLV-I gene products by PCR, but they had no lymphoma cells in peripheral blood or bone marrow. The fifth case showed negative signals by ISH and PCR. CONCLUSIONS: These findings suggest that some of the putative adult T cell leukemia/lymphoma (ATLL) types can be further classified as GI-tract-type lymphoma. The prognosis for the GI tract type is as poor as it is for conventional ATLL. PMID- 8431851 TI - Primary pulmonary plasmacytoma. AB - BACKGROUND: A patient was diagnosed with an extramedullary plasmacytoma of the lung after complete resection of the mass at thoracotomy. Immunoperoxidase staining of the mass revealed monoclonal lambda chains. Screening for multiple myeloma identified a small amount of M-protein in the blood, but no other evidence of multiple myeloma was found. METHODS: A literature search was conducted to determine the prognosis and the best way to manage the patient. RESULTS: Nineteen cases of primary pulmonary plasmacytoma were found in the literature. The age range was 3-79 years. Most of these cases were diagnosed at thoracotomy and treated by surgical excision. Immunohistochemical evaluation of the lesion is essential for diagnosis but was done in only three cases. CONCLUSIONS: Surgery and radiation therapy seem to be equally effective forms of treatment. The role of adjuvant chemotherapy is unknown. Local recurrences are rare. Follow-up data were inadequate to determine disease-free survival, progression to multiple myeloma, and overall survival in primary pulmonary plasmacytoma. Close follow-up is needed to detect progression. PMID- 8431852 TI - Solid variant of aneurysmal bone cyst. AB - BACKGROUND AND METHODS: Of the 200 cases of ABC in the Rizzoli Institute files, 15 had solid features on both gross and histologic examination. Inasmuch as fibrous proliferation with giant cell and bone production along with fibromyxoid areas and small aneurysmal spaces were found in the solid parts of the aneurysmal bone cyst, a grossly solid and radiographically osteolytic bone lesion with these microscopic features was called a solid aneurysmal bone cyst. Some authors call the same lesion extragnathic giant cell reparative granuloma. RESULTS: Sixty percent of the patients were female. The metaphysis was the preferred location in the long bones (8/11). Radiographic appearance was not specific, and sometimes a malignant lesion was very difficult to rule out. In seven patients, the lesion was considered radiographically "aggressive." Intralesional excision (curettage) in 12 patients and marginal resection in 3 patients with diaphyseal location was effective in controlling the lesion. No recurrence was detected after a mean follow-up of 59 months. CONCLUSIONS: High proliferative activity of the benign appearing proliferative spindle cells, often with fairly abundant mitoses, associated with benign giant cells and immature bone production are the features of this pseudosarcomatous hyperplastic lesion. It is sometimes is mistaken for a malignant tumor. PMID- 8431853 TI - Chordoma of the mobile spine. A clinicopathologic analysis of 40 patients. AB - BACKGROUND: Chordomas are lobulated neoplasms composed of physaliphorous cells and their precursors; some have atypical, epithelioid, or spindle cell features. Fewer than one-sixth of chordomas arise in the mobile (cervical, thoracic, or lumbar) spine. Forty-eight percent originate in the sacrococcygeal region and 39% in the sphenoocciput. METHODS: The study included 40 patients, 27 men and 13 women (2:1), with chordoma of the mobile spine. Their clinical and histopathologic features are described. RESULTS: Nineteen tumors (48%) were located in the cervical spine, 7 (17%) in the thoracic spine, and 14 (35%) in the lumbar area. Most patients underwent subtotal removal of the tumor and postoperative irradiation. Variations in histologic appearance, including an occasional chondroid background, did not affect biologic behavior. Twenty-three patients (58%) were alive 5 years after surgery. Eventually, 25 patients (63%) died of tumor. Metastasis developed in two patients (5%). In contrast to some other studies metastasis was a rare occurrence. CONCLUSION: Chordoma of the mobile spine is a slow-growing, recurring neoplasm of low metastatic potential that incapacitates by locally aggressive growth. PMID- 8431854 TI - Evidence of clonal progression in a case of Richter syndrome. AB - BACKGROUND: The debate continues as to whether Richter syndrome should be defined as non-Hodgkin lymphoma (NHL) because of a more malignant clone of neoplastic cells superimposed on preexisting chronic lymphocytic leukemia (CLL) or as the chance occurrence of two unrelated tumors. The cellular characteristics of the neoplastic clone involved in the CLL phase and the subsequent NHL were investigated in a patient in whom Richter syndrome developed. METHODS: Cell analysis was performed with immunofluorescence, histologic analysis, DNA extraction, and Southern blot analysis. RESULTS: The separated CLL and NHL B cells from blood and bone marrow, as well as the neoplastic cells in autopsy specimens of the organs affected by NHL, particularly the brain, were found to express the same light chain of surface immunoglobulin (SIg). The change MD-->M in the SIg heavy-chain expression and the appearance of cytoplasmic IgMk suggested isotype switching simulating that observed on the final phases of primary B-cell differentiation. This hypothesis was confirmed by Southern blot analysis of DNA from blood cells in the CLL phase and in Richter transformation, which showed that the two cell populations had identical Ig gene rearrangement. CONCLUSIONS: The NHL in the patient in this study represented a malignant progression of CLL, not a second lymphoid malignancy. PMID- 8431855 TI - Pernicious anemia and subsequent cancer. A population-based cohort study. AB - BACKGROUND: Elevated risk of cancers of the stomach, colon, and buccal cavity, as well as of lymphoma and leukemia, have been reported for patients with pernicious anemia in case reports and hospital-based and cross-sectional studies. METHODS: A cohort of 2021 men and 2496 women living in the Uppsala health care region in Sweden, discharged with a hospital diagnosis of pernicious anemia from 1965 to 1983, was followed for 20 years for subsequent risk of cancer. RESULTS: A total of 553 cancers were diagnosed among these patients, significantly more than expected based on cancer standardized incidence rates (SIRs) in the general population (SIR = 1.4; 95% confidence interval [CI], 1.2-1.5). Most prominent were excesses for cancer of the stomach (SIR = 2.9; 95% CI, 2.4-3.5), esophagus (SIR = 3.2; 95% CI, 1.8-5.2), and pancreas (SIR = 1.7; 95% CI, 1.2-2.4) among men and women; myeloid leukemia among men (SIR = 4.4; 95% CI, 1.8-5.2); and multiple myeloma among women (SIR = 2.5; 95% CI, 1.1-4.9). An excess of gastric carcinoid tumors also was evident in this cohort. The risk of stomach cancer was highest in the first year after diagnosis of pernicious anemia (SIR = 7.4; 95% CI, 5.3 10.1), but an increased risk persisted throughout the follow-up period. The risk of esophageal cancer also remained elevated throughout the study period, although the risk of pancreatic cancer dropped off after 5 years. CONCLUSIONS: This study confirms the excess risk of gastric carcinoma and carcinoid tumors associated with pernicious anemia, and suggests that the susceptibility state may extend to esophageal and other cancers. PMID- 8431856 TI - Cutaneous malignant melanoma of the head and neck. Analysis of treatment results and prognostic factors in 581 patients: a report from the Swedish Melanoma Study Group. AB - BACKGROUND: Results of surgical treatment of cutaneous malignant melanoma (CMM) have been highly variable, probably because of patient selection. Therefore, a study of representative patients with this disease was performed. METHODS: In a defined area of Sweden, 581 patients were analyzed. Clinical records and histopathologic findings were reviewed. The minimum follow-up time was 7 years. Prognostic factors were evaluated by the Cox proportional hazards model. RESULTS: Evaluation of sex distribution, age, and anatomic site of the primary tumor showed that the patients were representative of all Swedish patients with CMM of the head and neck. The mean patient age at diagnosis was 64 years for both sexes. Fifty-three percent of the patients were women. Female patients had more tumors of the face than did male patients, whereas male patients were overrepresented among patients with tumors of the auricle-external ear canal and scalp-neck area. Localization to the face was observed in 68%, which is an overrepresentation of three to four times when skin surface is taken into consideration. Twenty-four percent of the patients had lentigo maligna melanoma. Only 33% of the patients had superficial spreading melanoma. In univariate analyses, sex, anatomic site of the primary tumor, histogenetic type, Clark level of invasion, and tumor thickness had prognostic power. In a multivariate analysis, tumor thickness, anatomic site of the primary tumor, and sex of the patient were independent prognostic factors. CONCLUSIONS: In representative patients with CMM of the head and neck, tumor thickness, anatomic site of the primary tumor, and sex of the patients were independent prognostic factors. PMID- 8431857 TI - Localization and invasion by a soft tissue tumor induced by pellets made of hydroxypropylcellulose mixed with 20-methylcholanthrene in the femur of rats. AB - BACKGROUND: Pellets made of a carcinogenic substance, methylcholanthrene, admixed with a high molecular weight substance, hydroxypropylcellulose, were implanted into the thigh of 90 rats (three groups, 30 rats each). METHODS: In Group 1, the pellets were placed at the window made in the cortex of the femur; in Group 2, into the space between the dorsal femoral cortex and periosteum; and in Group 3, into the pouch created outside of the dorsal periosteum. RESULTS: Twenty weeks after implantation, rhabdomyosarcoma developed in 28 rats in Group 1, 27 in Group 2, and 21 in Group 3. Tumor invasions into the marrow of the femur were seen in 14 rats in Group 1 and 5 in Group 2. In Group 3, however, tumor invasion was not observed. There were significant differences in the invasion rate of tumor between Groups 1 and 2 (P < 0.01) and between Groups 2 and 3 (P < 0.05). At implant sites, Group 2 showed thinning out of the periosteum, whereas in Group 3 thickening of both cortex and periosteum was found. CONCLUSION: These experimental results are interpreted to mean that the periosteum provides an important barrier around the bone against tumor invasion into the bone. PMID- 8431858 TI - Malignant epithelioid hemangioendothelioma arising in an intramuscular lipoma. AB - BACKGROUND: A malignant epithelioid hemangioendothelioma (EH) developed within a peripheral intramuscular lipoma. It was seen as a painful calf mass. At the time of biopsy and en bloc resection, lung metastases were observed. METHODS: Radiologic, histologic, immunohistochemical, and ultrastructural features of the neoplasm are described, and the literature pertaining to EH is reviewed. RESULTS: The features of this tumor permitted its classification as a malignant EH. CONCLUSIONS: This case illustrates the potential for aggressive behavior in an EH, often considered to be a low-grade malignant neoplasm. Because such tumors can metastasize, they should be removed with wide margins whenever possible. This malignant neoplasm was located within a benign intramuscular lipoma, demonstrating the diagnostic problem that may exist in such a complex lesion. PMID- 8431859 TI - Recent trends in the incidence of in situ and invasive breast cancer in the Detroit metropolitan area (1975-1988). AB - BACKGROUND: Over the past two decades, breast cancer incidence rates have increased dramatically for women in all age groups. METHODS: Breast cancer incidence trends were evaluated in a population-based study of data from the Metropolitan Detroit Cancer Surveillance System, a participant in the Surveillance Epidemiology and End Results Program of the National Cancer Institute. Incidence rates from 1975 through 1988 were evaluated, based on tumor size, age at diagnosis, and race. RESULTS: Age-adjusted rates for all breast cancers have increased since 1975, with the largest change occurring since 1983. Age-adjusted incidence rates for ductal carcinoma in situ (DCIS) and cancers smaller than 2.0 cm were higher in white women than black women, whereas age adjusted incidence rates for larger tumors (> or = 2.0 cm) have been higher in black women since 1985. The rate of increase in incidence as measured by the average interval percentage change was highest for DCIS and small invasive tumors (< 1.0 cm) for all age groups of women. CONCLUSIONS: The more rapid increase in incidence of early breast cancer in the population suggests that the observed increase in breast cancer incidence over the last 2 decades may have resulted, at least in part, from a screening effect. PMID- 8431860 TI - Establishment and characterization of carcinosarcoma cell line of the human uterus. AB - BACKGROUND: The histogenesis of carcinosarcoma is still unknown. METHODS: A new human uterine cell line, EMTOKA, derived from a carcinosarcoma of the uterus, has been passed successfully in cell culture for more than 2 years. The cell line was established on April 11, 1989, in a uterine tumor of a 64-year-old Japanese woman who had a simple hysterectomy. The pathologic examination of the cultured material showed papillary and tubular adenocarcinoma (carcinomatous elements) and spindle-shaped fiber cells and chondrosarcoma (sarcomatous element). RESULTS: The cultured cells showed a cell-to-cell variability and at least five cell types, which included columnar cell, small epithelial cell, moderately sized or large epithelial-like cell, malignant tumor giant cell, and spindle cell types. The EMTOKA cells were transplantable to nude mice and produced tumors that consisted of the same carcinomatous and sarcomatous elements as those observed in the original tumor. The double labeling analysis of vimentin and cytokeratin showed that a large number of cultured cells had positive results for vimentin and a small number of cells had positive results for cytokeratin. Only a very small number of EMTOKA cells stained for vimentin and cytokeratin. The number of cells that expressed neither vimentin nor cytokeratin was very low. CONCLUSIONS: These findings may support the hypothesis that a uterine carcinosarcoma may be derived from a single stem cell that does not express both of the intermediate filaments. PMID- 8431861 TI - Prognostic factors in well-differentiated early-stage epithelial ovarian cancer. AB - BACKGROUND: The prognosis of patients with early ovarian cancer is good as compared with that of patients with advanced disease. However, there are no methods for predicting prognosis of early ovarian cancer, on which treatment decisions can be based. METHODS: The prognostic significance of DNA flow cytometric and morphometric analysis was evaluated in 64 surgically treated patients with well-differentiated early-stage (International Federation of Gynecology and Obstetrics [FIGO] Stage IA, IB, IC, and IIA) epithelial ovarian cancer. The extent of the well-defined staging procedure was assessed strictly in every patient. RESULTS: Only five patients died of recurrent ovarian cancer; all of these patients belonged to the inaccurately staged group. No significant relationship was found between clinicopathologic characteristics, such as menopausal status, FIGO stage, histologic cell type, and 5-year disease-free survival rate. Forty-two of the tumors had a mitotic activity index (MAI) of less than 30, and 43 of the tumors showed a volume percentage epithelium (VPE) of less than 65. Neither as a single parameter nor in combination did MAI and VPE correlate significantly with disease-free survival. Thirty-two tumors (50%) were DNA diploid, 15 were considered wide-CV-diploid, and 17 were aneuploid. Nearly 90% of the tumors showed DNA indices (DI) of 1.40 or less. The 5-year disease free survival rate was significantly lower (61%) for patients with DI greater than 1.40 than for those with DI of 1.40 or less (96%) (P < 0.005). From the total number of five patients who died of their disease, three had tumors with DI in the tetraploid range. PMID- 8431862 TI - Cytogenetic analysis of uveal melanoma. Consistent occurrence of monosomy 3 and trisomy 8q. AB - BACKGROUND: The genetic alterations associated with the pathogenesis of uveal melanoma have not been determined. To address this issue, the authors performed a prospective cytogenetic study of 35 uveal melanomas, including 23 primary untreated tumors and 12 tumors that were removed after local radiation therapy. METHODS: Representative tumor tissue was processed by established methods for histopathologic and cytogenetic studies. Tumor cells were disaggregated and established in short-term culture; metaphases were prepared by standard methods for karyotypic analysis. RESULTS: Successful analyses were achieved in 27 of the tumor specimens, including 20 of 23 tumors not exposed to radiation and 7 of 12 tumors exposed to radiation. All of the tumors had an abnormal karyotype. Recurrent chromosomal abnormalities detected in the tumors not exposed to radiation included monosomy 3 (13 of 20), trisomy 8 or 8q (11 of 20), loss of a sex chromosome (10 of 20), and loss of 6q (8 of 20). The tumors previously exposed to radiation were characterized by more complex changes, with monosomy 3 and trisomy 8q detected in three cases each. CONCLUSIONS: Uveal melanoma is characterized by monosomy 3 and trisomy 8q in most cases. These findings, which are supported by data from other investigators, provide compelling evidence that loss of gene sequences on chromosome 3 and duplication of gene sequences on chromosome 8 are implicated in the genetic alterations associated with uveal melanoma and offer a basis for additional molecular genetic investigations. PMID- 8431863 TI - Paragangliomas. Static cytometric studies of nuclear DNA patterns. AB - BACKGROUND: The biologic behavior of most paragangliomas cannot be predicted from their histologic appearance. Recently, cytometric studies have found an association between an aggressive clinical behavior and the presence of a hyperdiploid or tetraploid range in the DNA nuclear content. METHODS: The authors have studied morphometric (nuclear area and nuclear form factor) and DNA densitometric (integral optical density and DNA ploidy) features of 23 cases of paraganglioma by means of slide cytophotometry with the microTICAS system (University of Chicago, Chicago, IL). The samples were selected from paraffin embedded tissue, and representative sections were stained with the Feulgen technique. The differences between groups (cervical versus extracervical paragangliomas) were investigated with the Mann-Whitney test and Fisher discriminant linear function. RESULTS: The densitometric study showed aneuploid cell lines in 15 of 16 noncervical paragangliomas (with a DNA index within the tetraploid range), whereas 3 of 7 cervical paragangliomas were aneuploid and only 1 case did not have not a diploid cell line (with a DNA index within the peridiploid range). Mean ploidy (4.33 arbitrary units [AU] and 2.72 AU, respectively), nuclear area (58.74 microns 2 and 32.08 microns 2, respectively), the minor and major DNA indices (1.09-1.24 and 1.83-1.96, respectively), and DNA content variability (2c deviation indices [2cDI] of 8.62 and 1.88 AU, respectively) were higher in noncervical paragangliomas. With Fisher linear discriminant function, mean nuclear area (P = 0.0008), 2cDI (P = 0.0030), and the minor DNA index of each cell proliferation were correlated with location. None of the variables established statistically significant differences in comparisons of malignant and benign paragangliomas. CONCLUSIONS: Karyometric and DNA densitometric parameters have limited value in determining the prognosis of paragangliomas, although they are correlated with tumoral location, which is still an indicator in establishing the prognosis of these neoplasms. PMID- 8431864 TI - A panel of biomarkers of carcinogenesis of the upper aerodigestive tract as potential intermediate endpoints in chemoprevention trials. AB - BACKGROUND: Patients with squamous cell carcinoma of the head and neck have a 10 30% risk of developing a second primary tumor. The concept of "field cancerization" assumes that the whole upper aerodigestive tract is affected and prone to malignant transformation. This study was undertaken to investigate the value of a panel of monoclonal antibodies to identify biomarkers in oral mucosa associated with cancer risk. Such biomarkers may be suitable candidates to serve as intermediate endpoints in cancer chemoprevention trials. METHODS: As a model, the expression of antigens was assessed in cytologic preparations obtained from macroscopically normal oral mucosa of patients with tongue carcinoma and of controls. The panel consisted of antibodies against cytokeratin 8, 10, 13, and 19 and the monoclonal antibodies designated K931, K984, E48, Ki-67, and UM-A9. RESULTS: Oral mucosa of cancer patients had a more than threefold increased expression of cytokeratin 19 as compared with controls (36.0 versus 11.3%; P < 0.01). CONCLUSION: Cytokeratin 19 is a potential intermediate endpoint in head and neck cancer chemopreventive trials. PMID- 8431865 TI - Peripheral T-cell lymphoma with unique immunologic features. AB - BACKGROUND: The autologous mixed lymphocyte reaction (AMLR) is an important immunoregulatory phenomenon in human immune disorders. The authors have determined the phenotype and assessed the response of malignant lymph node T cells, from histologically and immunologically proven cases of peripheral T-cell lymphoma, in AMLR and allogeneic mixed lymphocyte reaction (MLR) and studied the secretion of lymphokines. METHODS: The proliferative response, tritiated 3H thymidine incorporation assay, was used to determine the AMLR and allogeneic MLR of the responding T-cells. An interleukin-2 (IL-2)-dependent T-cell line (CTLL) was used for the production of IL-2 by phytohemagglutinin-stimulated T-cells in a cytotoxic assay. B-cell growth and differentiation factor activity of T-cells was studied by enzyme-linked immunosorbent assay. RESULTS: The AMLR of malignant lymph node T-cells was increased characteristically in 12 of the 14 lymphoma cases studied; however, that of the blood T-cells was decreased. The allogeneic MLR of the malignant lymph node T-cells and blood-purified T-cells of the eight cases investigated was decreased. Expression or deficiency of CD2 and CD3 antigens on malignant T-cells did not show any difference in the AMLR assay. CONCLUSIONS: This study demonstrates an important tendency of malignant T-cells from patients with peripheral T-cell lymphoma to proliferate in AMLR. The highly augmented AMLR but deficient allogeneic MLR observed in these malignant T-cells indicate that autologous recognitive events may play an important role in the immunopathogenesis of this human disease. PMID- 8431866 TI - Cancer screening. Knowledge, recommendations, and practices of physicians. AB - BACKGROUND: Americans visit their primary care physicians several times a year. These visits provide physicians with many opportunities to reduce cancer risk in their patients by recommending periodic cancer screening. There is evidence of noncompliance among primary care physicians and their patients with regard to periodic cancer screening. Barriers to screening may be perceived by physicians and patients. RESULTS: The authors found that when physicians recommended cancer screening tests, the compliance among patients was relatively high. CONCLUSION: Primary care physicians can take the opportunity to recommend cancer screening tests during routine patient visits, and this strategy may well increase cancer screening rates in the population. PMID- 8431867 TI - Pharmacologic effects of cisplatin microspheres on peritoneal carcinomatosis in rodents. AB - BACKGROUND: A new drug-delivery formulation of cisplatin, whereby cisplatin was incorporated in lactic acid oligomer microspheres (CDDP-MS), has been developed in dosage form for peritoneal carcinomatosis and has been designed to release 70% of the incorporated cisplatin slowly during a period of 3 weeks. In this study, its pharmacologic effects were examined in rodents. METHODS: CDDP-MS was tested to determine (1) tissue distribution of cisplatin after intraperitoneal administration of cisplatin at 3.0 mg/kg body weight to rats, (2) acute toxicity in mice when injected intraperitoneally, and (3) therapeutic effects on peritoneal carcinomatosis induced by transplantable M5076 tumors in mice. RESULTS: These experiments revealed the following: (1) CDDP-MS resulted in a higher cisplatin concentration in tissues adjacent to the peritoneum for a longer period, and the concentration of cisplatin measured in the rest of the body was lower than that delivered by the cisplatin aqueous solution; (2) the 50% lethal dose value, determined by the Litchfield-Wilcoxon method, was 23.8 mg/kg body weight in CDDP-MS in terms of cisplatin, whereas in the cisplatin aqueous solution it was 13.5 mg/kg body weight; (3) CDDP-MS enhanced therapeutic effects when compared with the same toxicity dosage of cisplatin aqueous solution. CONCLUSIONS: Intraperitoneal CDDP-MS releases cisplatin into the peritoneal cavity for a long time, and it results in less systemic toxicity and greater therapeutic effects on peritoneal carcinomatosis than does cisplatin aqueous solution. PMID- 8431868 TI - Immune-mediated thrombocytopenia secondary to suramin. AB - The authors report a case of suramin-induced immune-mediated thrombocytopenia occurring in a patient on a Phase II protocol for treatment of metastatic renal cell carcinoma. On withdrawal of suramin, the acute and severe thrombocytopenia did not respond initially to plasmapheresis; subsequently, it resolved promptly and dramatically during the administration of intravenous gamma globulin, also coinciding with a decline in suramin blood levels. Results of immunologic and coagulation studies are reported and clinical implications discussed. PMID- 8431869 TI - Oncocytic variant of choroid plexus papilloma. Evolution from benign to malignant "oncocytoma". AB - BACKGROUND: The case of a left temporoparietal choroid plexus papilloma in a 12 year-old girl, which recurred 12 months after subtotal resection and apparent full recovery, is described. METHODS: The two consecutive surgical specimens were studied by light and electron microscopy. RESULTS: The first surgical specimen showed a tumor composed of cells with distended cytoplasm packed with numerous mitochondria characteristic of "oncocytic" change. Thus, tumor was the rare benign oncocytic variant of choroid plexus papilloma. A repeat histologic study of the recurrent tumor 12 months later showed evidence of malignant evolution in the form of multinucleated cells with frequent, often bizarre, mitotic figures. CONCLUSION: A rarely described oncocytic variant of choroid plexus papilloma that showed evidence of evolution from benign to malignant "oncocytoma" is discussed. PMID- 8431870 TI - Association of Langerhans cell histiocytosis with malignant neoplasms. AB - BACKGROUND: The association of Langerhans cell histiocytosis (LCH) with a malignant neoplasm is rare and generally has been the subject of isolated case reports. METHODS: A recent case of LCH seen at the University of Minnesota in combination with acute lymphoblastic leukemia led the authors to review their own charts from 1960 onward, in addition to the literature for other reported associations of LCH and malignant neoplasms. RESULTS: In addition to the presented case and 3 cases from the files of the authors, the literature contained 87 reported cases. Of the 91 patients, 39 had LCH with malignant lymphoma (ML); 25 of these cases were Hodgkin disease. In 11 of these 39 patients, the LCH was diagnosed from 12 months to 33 years after the ML was diagnosed. In 62% of the patients with LCH-ML (24 patients), the diagnosis was made concurrently and the Langerhans cells were found in the same lymph nodes. In the remaining four patients, the diagnosis of LCH preceded that of ML by 6-24 months. In 22 patients, including 2 patients in the files of the authors, LCH was reported in association with leukemia; 16 (73%) of these cases were associated with acute nonlymphoblastic leukemia. In two cases the leukemia preceded the LCH. In 6 patients both diagnoses were made concurrently, and in 14 patients (64%) the diagnosis of LCH preceded the diagnosis of leukemia by 8 months to 17 years. In the remaining 30 patients, LCH was associated with a variety of solid tumors, including a lung carcinoma in 12 patients. In all of these 12 cases the LCH was confined to the lung, and in 75% (9 of 12) of patients the diagnoses were made concurrently. In the 16 patients in whom the LCH preceded the solid tumor, the malignant diseases in 69% (11 of 16) developed within the radiation field used for the treatment of the LCH. CONCLUSIONS: The intimate and simultaneous association of LCH with ML and lung carcinomas suggests strongly that the process that leads to the association is a reactive one. However, in the patients with leukemia and the other solid tumors, the latency of the malignant neoplasm after the diagnosis of LCH is suggestive of a therapy-related process. PMID- 8431871 TI - Mental neuropathy (numb chin syndrome): a harbinger of tumor progression or relapse. PMID- 8431872 TI - A randomized trial of intrahepatic infusion of fluorodeoxyuridine with dexamethasone versus fluorodeoxyuridine alone in the treatment of metastatic colorectal cancer. PMID- 8431873 TI - Past pregnancy is associated with axillary node involvement in women with breast cancer. PMID- 8431874 TI - The past, the present, the future. AB - Lung cancer in women has replaced uterine cancer among the cancers causing the highest mortality in women. However, breast cancer remains a leading cause of death because of increasing incidence. Potential causes for the increase in both these diseases in women will be explored. An exciting development in recent years has been the clarification of the role of oncogenes in carcinogenesis. It appears that some cancers require multiple sequential mutations for malignant transformation to occur. This may be the model for the study of carcinogenesis. These developments in molecular genetics have important implications in screening, diagnosis, prevention, and in treatment strategies. We may be witnessing the beginning of the era of cell differentiation therapy. Retinoids have a potential for impacting on the treatment of neoplasms such as promyelocytic leukemia and oropharyngeal cancers. Understanding of the mechanism of cell differentiation may be forthcoming although molecular genetic studies. PMID- 8431875 TI - An overview of screening and early detection of gynecologic malignancies. AB - Reducing the toll of gynecologic cancer not only requires improving treatment, but also incorporating cancer prevention and detection strategies into clinical practice. Reviewing vulvar, cervical, endometrial, and ovarian cancer--their associated risk factors, mean of prevention and early detection, and signs and symptoms--alerts patients to the potential risks and the detection methods available. Discussing what behaviors, personal characteristics, family history, and exposures increase their risk; what behaviors reduce their risk; and what self-examinations and professional examinations may improve early detection permits health care professionals to write prescriptions for health. Neither major expenditure nor reorganization is required to incorporate cancer prevention and detection into existing clinical practice. Health care professionals who follow screening and detection recommendations appropriate in their own lives issue a consistent message and help bring patients into an active and responsibility-sharing partnership for better health. PMID- 8431876 TI - Radical hysterectomy for invasive cervical cancer. A 25-year prospective experience with the Miami technique. AB - BACKGROUND: The Miami modification of the traditional Wertheim-Meigs radical hysterectomy was used to treat Stage IB-IIA cervical cancer in a 25-year prospective study involving 978 patients. METHODS: The modifications included: vaginal reconstruction and closure using bladder and rectosigmoid serosa, retroperitoneal drainage through abdominal suction catheters, and suspension of the denuded ureters with the ipsilateral obliterated hypogastric artery. RESULTS: The overall corrected 5-year survival rate was 90.1%, with a surgical mortality rate of 1.4% and an overall urinary fistula rate of 1.4%. This fistula rate was significantly better than a 4.4% incidence rate in a literature survey. Although not measured, the Miami modification appeared to lengthen the vagina. CONCLUSIONS: Therefore, it was concluded that radical hysterectomy with the Miami modifications can be done safely in most patients with Stage IB-IIA cervical cancer. PMID- 8431877 TI - Radiation therapy of cervical cancer. New developments. AB - BACKGROUND: Invasive carcinoma of the cervix will be diagnosed in 13,500 women in the USA in 1992, of which a significant number will require radiation therapy. METHODS: Based on available information one can define optimal workup and staging, optimal radiation therapy, and the possibilities of interaction of radiation with surgery and chemotherapy in these cases. RESULTS: The pelvic tumor control rates achieved with radiation therapy can reach close to 100% in subclinical tumor (Stage IA), range from 91-98% in Stage IB, but can be as low as 25-34% in Stage IVA. Survival is affected by the presence of metastatic tumor deposits outside the pelvis, which when present in the inguinal or para-aortic nodal regions can be controlled with irradiation. The 5-year survival can be as high as 92% for carcinoma of the cervix Stage I and as low as 28% in Stage III. CONCLUSIONS: Radiation therapy can control the tumor in the pelvis in approximately 90% of patients with Stage I carcinoma of the cervix, but in only approximately 25% in patients with Stage IV disease. To increase tumor control, research is being conducted combining irradiation with chemotherapy, radiation sensitizers, hyperthermia, and new modalities such as neutron irradiation. Prophylactic para-aortic node irradiation is justified in some stages of the disease. PMID- 8431878 TI - Chemotherapy in advanced and recurrent cervical cancer. A review. AB - BACKGROUND: Despite the success of cytologic techniques in the diagnosis of neoplastic changes in the epithelium of the uterine cervix and the resultant decrease in the incidence of cervical invasive malignancies, 4440 women in this country will die of cervical cancer in 1992. Although radiation therapy and surgery form the basis for treatment of disease limited to the pelvis, those who have advanced disease or recurrences after locoregional therapy depend on systemic treatment for any hope of disease control. METHOD: Patients with advanced disease (not curable by surgery and/or irradiation) and recurrent cervical cancer have received single and combination cytotoxic chemotherapeutic regimens. RESULTS: Thirty-eight cytotoxic agents alone and in combination have been reported. Although none have produced a significant number of cures, several have shown moderate activity. Of particular interest, because of the relatively high response rates and carefully done trials, are cisplatin, ifosfamide, and dibromodulcitol with partial and complete response rates of 23%, 22%, and 22%, respectively. Currently, no combinations have been shown to be better than single agents. CONCLUSIONS: No chemotherapy for advanced or recurrent carcinoma of the cervix is more effective than single-agent cisplatin. The major thrust of current and future investigation seeks to identify additional active agents and to develop combinations that offer greater patient benefit. PMID- 8431879 TI - New approaches to high-risk cervical cancer. Advanced cervical cancer. AB - BACKGROUND: The role of chemotherapy in the surgical management of high-risk cervical cancer has not yet been defined. Based on the ability of numerous cytotoxic agents to induce regressions in advanced and recurrent cervical cancer, there is now a trend toward early use of these drugs. The efficacy of cisplatin containing regimens in particular suggests that new strategies combining chemotherapy and surgery may result in improved survival rates in patients with high-risk cervical cancer. METHODS: In this review of the literature, two groups of patients who may benefit from this approach to therapy are discussed. In the first group are patients with local or regionally advanced cervical carcinoma who receive chemotherapy (neoadjuvant) with the goal of reducing tumor bulk and thus allowing surgical treatment in normally inoperable cases. The second group consist of patients with identifiable adverse risk factors after radical hysterectomy and pelvic lymphadenectomy who receive postoperative chemotherapy (adjuvant) in an effort to decrease local and distant recurrences. RESULTS: The administration of neoadjuvant chemotherapy to patients with local and locally advanced cervical cancer allows radical surgery to be performed in many patients who otherwise would be considered inoperable. In these patients, there also appears to be a decrease in the incidence of pelvic and distant recurrences and possibly an improvement in survival rates. Adjuvant chemotherapy after radical surgery for patients at high risk for recurrence appears to provide a survival advantage in some high-risk patients. CONCLUSIONS: Preliminary results in the new approaches to therapy that combine chemotherapy with surgery in patients with high-risk cervical cancer are encouraging. Randomized prospective trials are warranted to identify the most active chemotherapeutic regimens and to determine the patient selection criteria most likely to result in improved survival rates. PMID- 8431880 TI - International Federation of Gynecology and Obstetrics staging of endometrial cancer 1988. AB - In 1988, the International Federation of Gynecology and Obstetrics (FIGO) Cancer Committee changed the staging of endometrial carcinoma from a clinical one to a surgicopathologic one. The emphasis in the new FIGO system was changed to the pathologic findings in the uterus, cervix, adnexa, and pelvic and/or periaortic nodes, and peritoneal cytologic findings. The major changes in this staging system were (1) the use of the depth of myometrial invasion and (2) the identification of tumor cells in peritoneal cytologic examination and of invasion in the retroperitoneal lymph nodes. Preoperative endocervical curettage was no longer necessary. Currently, the high level of operability of patients with endometrial carcinoma makes this staging system a viable one, which will provide information about the need for additional treatment. The use of the grading system for the tumor also was refined to upgrade nuclear changes that were inappropriate for the architectural grade. In serous adenocarcinomas, clear cell adenocarcinomas, and squamous cell carcinomas, nuclear grading took precedence. Adenocarcinomas with squamous differentiation were graded according to the nuclear grade of the glandular component. PMID- 8431881 TI - Virulence factors in endometrial cancer. AB - The majority of endometrial cancers are relatively benign and curable; there is a subset of virulent tumors that demands recognition. Factors that must be evaluated include: tumor grade, ploidy, steroid receptors, myometrial invasion, lymph node status, extrauterine disease or positive peritoneal fluid, and certain special tumors. These tumors of special virulence include: papillary adenocarcinoma, papillary serous adenocarcinoma, adenosquamous carcinoma, and clear cell carcinoma. Virulent tumors (approximately 20%) require special consideration and special treatment. PMID- 8431882 TI - Prognostic significance of hormone receptors in endometrial cancer. AB - BACKGROUND: Endometrial carcinoma is the most common female pelvic genital malignancy. Many studies suggest that approximately 75% of all endometrial cancers are clinical Stage I. More than 50% of cancer deaths are in patients with clinical Stage I disease. As a result, prognostic factors have been evaluated in an attempt to identify those patients with presumed early stage disease who will be at high risk for recurrence. Recently, hormone receptor status (estrogen [ER], progesterone [PR]) in endometrial cancer has been suggested to be a prognostic factor. METHODS: Two hundred seventeen patients with Stage I and II endometrial cancers were evaluated for cytoplasmic steroid-receptor status. These results were compared with other prognostic factors in both univariant and multivariant analysis. RESULTS: When ER and PR and combined ER/PR status were analyzed separately, patients with receptor-positive lesions had significantly better disease-free survival than those with receptor-negative lesions. The receptor status was also a significant independent prognostic factor when evaluated by stepwise proportional hazards regression analysis. CONCLUSIONS: Hormone receptor status in endometrial cancer appears to be an important prognostic factor. PMID- 8431883 TI - Endometrial carcinoma. Influence of prognostic factors on radiation management. AB - The earliest intracavitary radium treatment for uterine cancer was reported in 1908. Refinements reported during the next 20 years, using an intrauterine tube and colpostats or radium capsules, established a treatment philosophy of preoperatively irradiating uterine and parauterine tissues. Thus, preoperative intracavitary irradiation became entrenched as therapy for all endometrial cancers for the better part of four decades. In the 1950s and 1960s, the ability of external irradiation to eradicate cancer in regional lymphatic vessels prompted the use of pelvic field irradiation in Stage II and III and recurrent disease. The results of surgical exploratory studies in the 1970s established more refined criteria for preoperative or postoperative external pelvic irradiation in high-grade infiltrating Stage I cancers. In the 1980s, it became apparent that, for tumors with lymphovascular invasion, clear cell, and serous papillary histologic types, the disease spread to the upper abdomen and the paraaortic nodes might benefit from extended field and/or whole abdominal irradiation, with or without systemic bolus or concomitant continuous-infusion chemotherapy. In the 1980s, a subset of patients was identified with high-grade lymphovascular invasion clear cell and papillary serous histologic types or with positive peritoneal cytologic findings who were at high risk of failing in the paraaortic nodes and/or the upper abdomen for whom extended field or whole abdominal irradiation have been advocated. Given the fraction and dose limitation for a large abdominal field, the addition of systemic concomitant bolus or continuous infusion of chemotherapy currently is proposed to improve the control of intraabdominal failure in these high-risk patients. PMID- 8431884 TI - Epidemiology of breast cancer. Findings from the nurses' health study. AB - BACKGROUND: The epidemiology of breast cancer was reviewed in the context of hormonal, hereditary, histologic, and dietary risk factors. METHODS: Literature review. RESULTS: Late age at menarche and early age at first birth decrease the risk of breast cancer as does an early age at menopause. These risk factors relate to the lifetime exposure of the breast tissue to ovarian hormones. Although an early first birth is associated with a transient increase in the risk of breast cancer, perhaps as a result of the breast's exposure to high levels of hormones before terminal differentiation, in older women, parity is associated with a decreased risk of breast cancer. Among postmenopausal women, obesity is associated with higher levels of estrogens and an increased risk of breast cancer. Within the strata of breast cancer stages at diagnosis, obesity is associated with increased mortality, again supporting the influence of endogenous estrogens on this disease's incidence, recurrence, and survival rates. Consistent with these relationships, current use of estrogen therapy among postmenopausal women is associated with an increased risk of breast cancer. A family history of breast cancer is associated with approximately a two-fold increase in the risk of breast cancer, and this risk is greater if the diagnosis was made when the woman's mother was young, although even a diagnosis in an older mother is associated with an increased risk in her daughters. The follow-up of women with a history of benign breast biopsy results shows that atypical hyperplasia is associated with a fourfold increase in risk compared with a biopsy specimen without proliferative changes. Atypia doubles the risk. These data support the concept of atypia as a precursor lesion for breast cancer and may warrant its use as a marker in further studies. Consistent data from retrospective and prospective studies show a positive association between moderate alcohol intake and the risk of breast cancer. This may reflect the increase in estrogen levels observed among women who consume alcohol. Data from prospective studies do not support a relationship between dietary fat intake and the risk of breast cancer either in premenopausal or postmenopausal women. CONCLUSIONS: Few of these associations offer the potential for intervention to reduce the breast cancer risk. PMID- 8431885 TI - Hormone-replacement therapy in patients with breast cancer. A reappraisal. AB - BACKGROUND: It has been common practice to prohibit hormone-replacement therapy (HRT) in patients with breast cancer. A reappraisal of this practice is necessary because hundreds of reports have established the benefits of HRT in coronary artery disease, osteoporosis, the serum lipid profile, and quality of life. METHODS: An argument is presented to support the safety of HRT use in such patients in the absence of a prospective randomized study addressing these issues. This argument relies primarily on historical data. RESULTS: There is no direct evidence that the use of HRT adversely affects patients who have previously been afflicted with breast cancer. CONCLUSIONS: A prospective randomized study is essential to resolve this issue. In the meantime, patients should be counseled regarding the theoretical adverse effects of HRT versus the proven beneficial effects and the final decision for its use rests with the patient. PMID- 8431886 TI - The estrogenic activity of synthetic progestins used in oral contraceptives. AB - BACKGROUND: Oral contraceptives (OC) contain an orally active estrogen in combination with an orally active synthetic progestin derived from 19 nortestosterone. OC have had an enormous positive impact on public health for the past three decades, and in the main, there has been a remarkably low incidence of troublesome side effects. Although estrogens are implicated in an increased incidence of breast and endometrial cancer, epidemiologic studies have not provided convincing evidence to support a direct correlation between OC use and an increase in breast cancer incidence. By contrast, OC do cause a decrease in the incidence of endometrial and ovarian carcinoma. During the past decade, several isolated reports have linked an increased incidence of breast cancer with the use of synthetic progestins. No mechanism for the proliferative potential of progestins has been offered. Therefore, the authors investigated this problem to formulate a hypothesis, based on laboratory data, that might be evaluated in populations at risk. METHODS: The synthetic progestins (19-nortestosterone derivatives) chosen for the study were norethynodrel, norethindrone, norgestrel (levonorgestrel), and gestodene. These were compared with the actions of medroxyprogesterone acetate (MPA). To determine whether the progestins produced their effects via the ER, the cells were transfected with a chloramphenicol acetyl transferase (CAT) reporter gene containing an estrogen response element only activated by ER. RESULTS: The 19-nortestosterone derivatives all stimulated the growth of estrogen receptor (ER)-positive but not ER-negative breast cancer cells in culture. Antiestrogens, but not the antiprogestin mifepristone (also known as RU 486), inhibited progestin-stimulated cell proliferation. MPA did not stimulate cell proliferation. All the synthetic progestins that increased replication also activated CAT. Activation was blocked by antiestrogens but not by mifepristone; the synthetic progestin MPA was inactive. CONCLUSIONS: These studies provided direct evidence that some synthetic progestins exert estrogenic effects through the ER. The results demonstrated that progestins can have a dual effect on estrogen target tissues either to stimulate or differentiate cells. The results suggest that some beneficial estrogen-like effects could be produced by synthetic progestins (e.g., bone preservation), but epidemiologic studies of OC use should focus of the "total estrogen" content to establish whether some formulations place some groups of women at greater risk of having breast cancer. PMID- 8431887 TI - Age-specific differences in the relationship between oral contraceptive use and breast cancer. AB - BACKGROUND: Nearly all studies have suggested that the use of oral contraceptives (OC) is not associated with the aggregate risk of breast cancer diagnosed in women aged 20-54 years. Because of age-specific differences in the breast cancer parity relationship and because of age-specific differences in other breast cancer risk factors, the Centers for Disease Control reexamined data from the Cancer and Steroid Hormone Study (CASH) to assess whether OC use has different effects on the risk of breast cancer at different ages of diagnosis. METHODS: This population-based case-control study was designed to examine the relationship between the use of OC and the risk of breast, ovarian, and endometrial cancer. CASH was conducted in eight geographic areas in the United States during 1980 1982. All participants were interviewed at home with a pretested standardized questionnaire including a calendar of life events and a photograph book of all pills marketed in the United States. RESULTS: We found that the relationship between the risk of breast cancer and OC use appeared to vary by the age at diagnosis. Among women aged 20-34 years at diagnosis or interview, those who had ever used OC had a slightly increased risk of breast cancer (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.0-2.1) compared with women of the same ages who had never used OC. Among these women, there were no trends of increasing or decreasing risk with any measure of OC use. Among women aged 35-44 years, there was no association between OC use and breast cancer. Among women aged 45-54 years, those who used OC had a slightly decreased risk of breast cancer (OR, 0.9; 95% CI, 0.8-1.0). Among these women, risk estimates decreased significantly with increasing time since first and last use. CONCLUSIONS: Although the slightly increased risk estimates for the youngest women were compatible with findings by other investigators, the decreased risk estimates for the oldest women have not been described in as many studies. Available data provide no reasons to change prescribing practices or the use of OC that are related to the breast cancer risk. PMID- 8431888 TI - Breast cancer. Challenge and responsibility. AB - The diagnosis and treatment of breast cancer has changed dramatically during the last quarter century, a fact perhaps not fully appreciated by many primary care physicians. Breast cancer presents a number of challenges for the obstetrician/gynecologist. The disease is common and the mortality rate is second only to lung cancer. The appropriate role for the obstetrician/gynecologist is one of surveillance, including taking a history and physical examination and selected diagnostic studies, and as a resource for patients, including a discussion of risk factors and treatment alternatives. Because of the increasing involvement of obstetrics and gynecology in molecular genetics and hormone interactions, basic research in genetic alterations and hormonal therapy directed toward decreasing morbidity from cardiovascular disease and osteoporosis is recommended. PMID- 8431889 TI - Ovarian cancer screening. AB - BACKGROUND: Despite advances in evaluation and treatment, ovarian cancer mortality has decreased minimally during the past two decades. Most patients have advanced-stage disease at diagnosis, and the prognosis is poor. As a result, there has been increasing interest in the development of methods for the early detection of ovarian cancer. To benefit from screening, a disease should (1) be a significant cause of mortality, (2) have a high prevalence in the screened population, (3) have a preclinical phase that can be detected by screening, and (4) be amenable to therapy, such that the survival rate of patients with early stage disease is significantly higher than that of patients with advanced-stage disease. Ovarian cancer fulfils all of these criteria. METHODS: An optimal screening method should be safe, easy to do, time efficient, and acceptable to the patients being screened. Most importantly, it should have a high sensitivity and specificity. RESULTS: Currently, the most effective screening methods for ovarian cancer are serum CA 125 levels and transvaginal sonography (TVS). In screening studies, the serum CA 125 level has had a reasonably high specificity but a low sensitivity. Currently, approximately 8000 asymptomatic women have been screened with TVS. Ten primary ovarian cancers were detected, and all were Stage I lesions. Patients whose tumors were detected by TVS all have been cured by conventional treatment. TVS screening has resulted in a significant reduction in stage at detection and in the case-specific death rate from ovarian cancer. In these studies, TVS has had a high sensitivity but only a moderate specificity. CA 125 level, Doppler flow sonography, and the use of a morphology index are being evaluated as methods to increase the specificity of TVS. CONCLUSIONS: A large multiinstitutional study is indicated to determine if annual TVS screening will cause a significant decrease in site-specific mortality from ovarian cancer. PMID- 8431890 TI - Prophylaxis in ovarian cancer. AB - The only prophylaxis for ovarian cancer is oophorectomy, except in the very rare case when an ovarian cancer appears to arise from the mesothelial tissue of the abdominal cavity. It has been shown that women who have taken the oral contraceptive pill for 4 or 5 years decreases the incidence of ovarian cancer by approximately 40%. It is estimated that the oral contraceptive pill can prevent approximately 1500 ovarian cancers each year. The postmenopausal palpable ovary syndrome is simply the palpation of what is interpreted as a normal-sized ovary in the premenopausal woman represents an ovarian tumor in the postmenopausal woman. It addresses the size and consistency and has nothing to do with the small cysts reported by the sonographer. A patient who has two first-degree blood relatives or a mother, sister, or daughter who has developed ovarian cancer premenopausally is at high risk to develop ovarian cancer. Because ovarian cancer is the leading cause of death from gynecologic cancer, it is important to explore all options for prophylaxis in the prevention of ovarian cancer. PMID- 8431891 TI - Surgical staging and cytoreductive surgery of epithelial ovarian cancer. AB - BACKGROUND: Surgery remains the cornerstone of the treatment for epithelial ovarian cancer. In early ovarian cancer, the initial operation is a complete assessment of the spread of disease. In this staging operation, 33% of patients thought to have either Stage I or II tumors will be found to have advanced-stage disease. The correct diagnosis of advanced disease prevents improper treatment of patients originally thought to have early disease. For patients with advanced disease, the initial cytoreductive operation reduces tumor bulk and produces increased sensitivity to chemotherapy for the remaining tumor. The principles of cellular kinetics provide good theoretic evidence for the benefit of cytoreductive surgery. METHODS: Current studies relating to primary and secondary surgical cytoreduction of epithelial ovarian cancer were reviewed. RESULTS: Current indirect evidence indicates a significant survival benefit for patients with epithelial ovarian cancer who undergo successful surgical cytoreduction. Several recent studies also have shown the importance of the biology of the tumor, the extent of tumor spread, the location of the tumor, the cell type, the histologic grade, and the age of the patient. Although the literature contains fewer reports of secondary cytoreductive surgery than of primary cytoreductive surgery at the time of second-look, surgical reassessment appears to provide a survival benefit. CONCLUSIONS: The potential benefit of secondary cytoreduction will be increasingly important as new salvage therapies become available. PMID- 8431892 TI - Primary treatment of epithelial ovarian malignancies. PMID- 8431893 TI - Second-look operation in ovarian cancer. AB - BACKGROUND: Although second-look laparotomy (SLL) remains the hallmark method for determining disease status after completion of adjuvant therapy, the inclusion of reassessment surgery in the treatment scheme of ovarian carcinoma has been challenged. Given the absence of prospective analyses addressing this issue, justification for continued use of SLL must demonstrate benefits regardless of the outcome of the procedure. RESULTS: In the absence of residual disease, either the recurrence rate after SLL should be acceptably low or the outcome should permit identification of specific groups that would benefit from consolidation therapy. The characteristics associated with a significant risk for recurrence after a negative SLL include patient age, histologic grade, and the amount of residual disease after the primary cytoreduction operation. The postoperative benefits of positive SLL findings must be manifested in enhanced survival rates after secondary cytoreduction surgery, salvage therapy, or both. Recent evidence suggests that tumor reduction during SLL and contemporary salvage methods favorably influence specific subgroups of patients. CONCLUSIONS: The criteria for continued use of SLL in advanced epithelial ovarian cancer should include the availability of (and preferably prospective clinical trials for) both consolidation and salvage therapy to which all patients with ovarian cancer optimally would be afforded access. PMID- 8431894 TI - Intraperitoneal chemotherapy in the management of ovarian cancer. AB - During the past decade, intraperitoneal therapy of ovarian cancer has evolved from a pharmacologic model into an established treatment technique for women with this malignancy. Approximately 40% of patients with small-volume residual ovarian cancer (microscopic disease or macroscopic tumor, < or = 0.5 cm in maximum tumor diameter), after an objective response to initial organoplatinum-based systemic chemotherapy, may have a surgically documented complete response to platinum based intraperitoneal chemotherapy. Patients who have not responded to systemic platinum administration rarely will respond to the drug given intraperitoneally, despite the presence of only small-volume residual disease when this regional treatment strategy is used. Other agents with antineoplastic activity after intraperitoneal administration in women with ovarian cancer include mitoxantrone, taxol, alpha-interferon and gamma-interferon, and interleukin-2. Although intraperitoneal therapy currently is being examined as a component of the initial chemotherapeutic program for patients with ovarian cancer, a precise role for regional drug delivery in this clinical setting remains to be defined. PMID- 8431895 TI - Cell growth regulation in epithelial ovarian cancer. AB - BACKGROUND: As in the case of other epithelial neoplasms, most ovarian cancers arise from single clones of cells that have undergone multiple genetic alterations. A comparison of normal and malignant ovarian epithelium has identified several differences in growth regulation by peptide growth factors, protooncogenes, and tumor suppressor genes. METHODS: Recent articles and abstracts have been reviewed. RESULTS: The malignant ovarian epithelial phenotype has been associated with (1) autocrine growth stimulation by transforming growth factor-alpha, (2) loss of autocrine growth inhibition by transforming growth factor-beta, (3) mutation or amplification of ras in 2-12% of cases, (4) amplification of myc in 23% of specimens, (5) expression of fms in 56% of cases with potential autocrine stimulation by macrophage colony stimulating factor, (6) paracrine stimulation by macrophage products including interleukin-1, interleukin 6 and tumor necrosis factor, (7) overexpression of c-erbB-2 (HER-2/neu) in 30% of cases, and (8) mutation with consequent overexpression of p53 in 50% of advanced ovarian cancers. A poor clinical prognosis is associated with expression or overexpression of the epidermal growth factor receptor, fms, and HER-2/neu. Antibodies against the extracellular domain of the HER-2/neu gene product p185 inhibit the growth of tumor cells that overexpress HER-2/neu and are associated with marked decreases in diacylglycerol levels. The intracellular kinase domain is required for growth inhibition. Antibodies that inhibit growth stimulate phosphorylation of intracellular substrates. Ricin A chain monoclonal antibody conjugates that react with p185 also inhibit the growth of tumor cells that overexpress p185. The intracellular kinase region is not required for immunotoxin mediated killing. Coexpression of HER-2/neu and the epidermal growth factor receptor has been observed in 65% of epithelial ovarian cancers and in a limited number of normal tissue from a fraction of donors. CONCLUSIONS: Multiple alterations in growth factors, protooncogenes and growth factors have been detected in different epithelial ovarian cancers. Inappropriate signalling from receptor tyrosine kinases may be particularly important for ovarian oncogenesis. Drugs that affect tyrosine kinase and phosphatase activity deserve attention as potential therapeutic agents for ovarian cancer. The extracellular domains of the HER-2/neu gene product p185 and the epidermal growth factor receptor may provide useful targets for serotherapy. PMID- 8431896 TI - Monoclonal antibodies in the management of ovarian cancer. A clinical perspective. AB - Despite recent advances in the conventional management of ovarian cancer, this disease remains the leading cause of death among the gynecologic malignancies, killing more American women each year than all other gynecologic cancers combined. As a tumor arising from a nonessential organ that remains primarily confined to the peritoneal cavity, ovarian cancer makes an attractive target for monoclonal antibodies (MoAb). Several MoAb have been developed that have actual or potential clinical use in the management of ovarian cancer. Serum assays using a MoAb against an ovarian cancer-associated antigen (CA 125) are currently in routine clinical use for monitoring the course of disease in women with known ovarian cancer. Such assays may play a role in multitechnique screening programs. Radiolabeled antibodies are under study for use in external imaging or intraoperative detection of ovarian cancer. Isotope-labeled antibodies also are being evaluated in the treatment of ovarian cancer as are antibodies coupled to drugs or biologic toxins. Some antibodies may have direct antitumor effects through binding to biologically active receptors or through immune effector functions. The use of antibody fragments, chimeric antibodies, human antibodies, and genetically engineered antibodies is under active investigation. MoAb have important potential for improving the diagnosis, monitoring of response to therapy, and treatment of ovarian cancer. PMID- 8431897 TI - Chemosensitivity testing in ovarian cancer. AB - Most patients with ovarian cancer currently are treated primarily with surgery and chemotherapy. Drug selection usually is not based on individualized in vitro sensitivity studies but on reported response rates of clinical trials. Attempts to include in vitro chemosensitivity testing into the management of ovarian cancer have been disappointing to clinicians. Tumor cells from fresh human ovarian cancer do not grow well under artificial in vitro growth conditions. The selection of cells that happen to proliferate in vitro (e.g., human tumor clonogenic assay) has resulted in low plating efficiencies (0.001-0.1% of plated cells). The vigorous mechanical and enzymatic tumor disaggregation, done to obtain a single-cell suspension, further reduces the number of cells that grow in vitro, resulting in low overall evaluability rates of 40-70% for the human tumor clonogenic assay. At the University of Miami, a new in vitro chemosensitivity assay was developed that detected the decrease in total tumor cell viability by measuring intracellular adenosine triphosphate as a function of in vitro drug response. Preliminary data on 31 tumor tissues from patients, which was evaluated with this method, showed a sensitivity of 92% and a specificity of 100%. Since these initial studies, data were gathered on more than 150 fresh gynecologic tumor specimens to evaluate single drugs and drug combinations at five concentrations (range, 10-500% of reported peak plasma concentrations). The evaluability rate for ovarian tumors was more than 90%. Some tumors showed almost complete cell kill at the lowest drug concentration; others had only a limited response at the highest level. Drug-response patterns also were variable for combined drug exposure. These findings underscore the heterogeneity of drug response in morphologically similar tumors and the importance of characterizing individual chemosensitivity profiles for patients before drug treatment. PMID- 8431898 TI - Flow cytometric evaluation of ovarian cancer. AB - BACKGROUND: Despite recent advances in the treatment of ovarian cancer, the long term prognosis for patients with this malignancy appears to depend more on tumor prognostic factors than on treatment regimens. The traditionally used prognostic factors are often subjective and, currently, have not been sufficient to determine individual patient prognosis. METHODS: Newer techniques of quantitative cytologic testing, including flow cytometry, facilitate the objective evaluation of tumor cell heterogeneity and the identification of additional prognostic factors. RESULTS: There is good evidence, mainly from retrospective studies, that DNA ploidy is a valuable prognostic indicator in patients with both early-stage and late-stage ovarian cancer. Most of the recent flow cytometric studies have identified ploidy as an independent prognostic factor, with aneuploidy predicting a significantly shorter survival time, even in patients with borderline malignant tumors. Flow cytometric determination of cell cycle information (e.g., S-phase fraction or proliferative index) may represent additional prognostic information and may be used to predict the early tumor response to treatment. CONCLUSIONS: Although additional prospective studies are needed to establish the exact value of flow cytometric evaluation for ovarian cancer and other gynecologic malignancies, there is little doubt that the prognostic value of this information will influence clinical management of patients with these malignancies in the near future. PMID- 8431899 TI - National survey of ovarian carcinoma. I. A patient care evaluation study of the American College of Surgeons. AB - BACKGROUND: The Commission on Cancer of the American College of Surgeons recently finished a national survey of patients with ovarian cancer patients. The goal was to compare the patterns of care over a 5-year period. METHODS: Data were collected from 25 consecutive patients whose disease was diagnosed first at 904 hospitals with cancer programs in 1983 and 1988. RESULTS: There was a total of 12,316 patients, of whom 80% were 45-85 years old. Contrary to popular belief, only 8.2% of patients were nulliparous; 85% of patients had one to five children. Of significance, 18.2% of patients with ovarian cancer had undergone a previous hysterectomy with ovarian preservation. Primary surgical treatment was used in 94.9% of patients and consisted of: oophorectomy, 81.9%; hysterectomy, 55.1%; and omentectomy, 59.0%. However, only 12-25% of patients had biopsies of the diaphragm, paracolic gutters, colon, small bowel, pelvic and paraaortic lymph nodes, and cul-de-sac to permit adequate surgical staging. The primary surgeons were: gynecologic oncologists, 21%; obstetrician-gynecologists, 45%; general surgeons, 21%; and others, 13%. CONCLUSIONS: These data indicate that additional resources are needed to improve the care of patients with ovarian cancer. PMID- 8431900 TI - Imaging in gynecologic malignancies. AB - Cross-sectional imaging is often a useful complement to clinical examination in patients with gynecologic malignancies. Patients with ovarian cancer will benefit less from the use of computed tomography and magnetic resonance imaging (MRI); however, extensive intraperitoneal disease may be evaluated and followed with either technology. Endometrial cancer is best approached by staging with contrast enhanced MRI. The more advanced the disease is, the more information should be available from MRI imaging. By contrast, patients with cervical cancer are assessed best using noncontrast-enhanced MRI as far as imaging of the primary tumor is concerned. Extracervical extension is defined better with contrast enhancement and varied pulse sequences. Radiation changes and tumor response also can be assessed with MRI imaging as a complement to clinical examination. PMID- 8431901 TI - New advances in radiation oncology for gynecologic cancer. AB - In 1992, the American Cancer Society anticipates that there will be 1,130,000 new cases of invasive cancer diagnosed in the United States. About 66,500 will be invasive cancers of the cervix, uterus, and ovary. About 22,400 patients will die during 1992, with 50-60% of those deaths being due to persistent local regional disease. Data are available to suggest that a reduction in local failure will be reflected by an increase in survival free of disease. In 1992, major efforts are being made to reduce the incidence of local failure. Three areas in this regard are innovative uses of brachytherapy, intraarterial chemotherapy and radiation therapy, and continuous infusion chemotherapy and radiation therapy. These new techniques show significant reduction in local failure with associated improvement in survival. The data will be presented to illustrate the impact of these techniques. PMID- 8431902 TI - Neovaginal reconstruction. AB - Formation of a neovagina is an important step in restoring a normal self-image for the woman who has had treatment for gynecologic cancer. There are several techniques that the surgeon may select based on the amount of tissue removed or damaged, the surrounding anatomy, and the condition of the patient. The indications, techniques, and results of these procedures will be described in this article. PMID- 8431903 TI - Low colorectal anastomosis and reconstruction after gynecologic cancer. AB - Radical en bloc resection of pelvic tissue remains an important part of the armamentarium of the gynecologic oncologist despite significant advances in radiation oncology and chemotherapy. Total pelvic exenteration can be the only hope of women who have not responded to more conservative therapy. The time has come where it is appropriate to use contemporary techniques in the discipline of reconstructive surgery to restore these women to an acceptable quality of life. It may be the next challenge for the pelvic surgeon to participate in such surgical reconstruction. This challenge is becoming an active part of the oncologic surgical practice in head and neck and breast surgery. This article reviews the techniques that are available in the reconstruction of a functional rectum with elimination of colostomy. PMID- 8431904 TI - Functional characteristics and follow-up of the continent ileal colonic urinary reservoir. Miami pouch. PMID- 8431905 TI - Conservative management of early vulvar cancer. AB - There is a definite trend toward vulvar conservation and individualized management of patients with early vulvar cancer. This approach initially was used only for patients with T1 disease, but with increasing experience with conservative surgery and the integration of postoperative adjuvant radiation when appropriate, some investigators have broadened the indications to include carefully selected patients with T2 lesions. A recent literature review suggests that the local invasive recurrence rate for T1 disease is 7.2% (12 of 165) after radical local excision compared with 6.3% (23 of 365) after radical vulvectomy (P = 0.85). Surgical margins must be at least 1 cm, and the rest of the vulva must be healthy if an increased local recurrence rate is to be avoided. Local recurrences usually can be treated successfully if diagnosed early, but recurrence in the groin is usually fatal. Inguinal-femoral lymphadenectomy should be done on all patients if the primary tumor is more than 2 cm in diameter and in patients with T1 disease in whom the depth of invasion is greater than 1 mm. Separate groin incisions may be used, but pelvic and groin irradiation should be given if there is at least one large node replaced with tumor or multiple nodes containing micrometastases. Careful patient selection is critical if modified operations are used, or an increased rate of recurrence will follow. PMID- 8431906 TI - Predicting sexual and psychologic morbidity and improving the quality of life for women with gynecologic cancer. AB - The research progress made in the 1980s on understanding psychologic outcomes after gynecologic cancer has continued since the 1986 conference. To facilitate future intervention research, a model for predicting the risk for psychologic and behavioral morbidity is provided. This model clarifies psychologic, behavioral, and medical routes leading to a reduced quality of life. Although few intervention studies have been conducted with gynecologic patients, studies in other patients with cancer suggest that psychologic interventions can reduce emotional distress, enhance coping, and improve general adjustment and sexual functioning, in particular. The final section of this article discusses future research directions and challenges institutions and study groups to support quality-of-life research for women with gynecologic cancer. PMID- 8431907 TI - Gynecologic Oncology Group randomized trials of combined technique therapy for vulvar cancer. AB - The Gynecologic Oncology Group (GOG) did a surgicopathologic study of vulvar cancer in which various prognostic factors in the primary lesion were evaluated and compared with the pathologic status of the lymph nodes in the groin dissections. In total, 558 patients were entered into this study (GOG Protocol 36) from November 1977 to February 1984. The 203 patients with positive groin nodes were eligible for a second study in which they were assigned randomly to receive either pelvic lymph node dissection or pelvic and groin irradiation (Protocol 37). One hundred fourteen patients were randomized to this study, and 53 of 59 patients in each treatment arm actually underwent the prescribed treatment. Acute and late toxicities were similar in both treatment arms. There was a significant difference in survival rate that favored the pelvic radiation treatment (P = 0.03). The largest difference in survival rates occurred in those patients with either of the poor prognostic findings (clinically suspicious fixed ulcerated nodes or two or more positive nodes). The 2-year survival rate was 68% for the radiation treatment arm and 54% for the surgical program. Pelvic radiation therapy has become the standard treatment for patients with positive groin nodes, especially if they are fixed or multiple. Based on these results, a subsequent study was designed to test whether radiation therapy could substitute for bilateral groin node dissection in patients with vulvar cancer (Protocol 88). Fifty-eight patients were enrolled in the study before entry was suspended on April 30, 1991, and the study was closed on November 1, 1991. In the first 49 evaluable patients, there were five groin recurrences in the irradiated patients, although there were no groin failures in the operated group. The radiation program used in this study may not have provided an adequate dose to the depth where the lymph nodes were located because the prescription called for dose calculations at a depth of 3 cm. Unless demonstrated in another study, groin irradiation cannot be used as an equivalent option to groin dissection. Aggressive preoperative chemoradiation treatment currently is being studied for patients with T3 lesions not amenable to standard radical vulvectomy. Surgical dissection of residual tumor plus bilateral groin dissections are to be done if the postradiation biopsy findings are positive. Patients with unresectable Stage T2 or T3 groin nodes are also eligible for this study (Protocol 101). PMID- 8431908 TI - Carcinoma of the cervix treated with chemotherapy and radiation therapy. Cooperative studies in the Gynecologic Oncology Group. AB - Since its inception in 1970, the Gynecologic Oncology Group (GOG) has pursued a series of Phase II and III cooperative clinical investigations of the combination of cytotoxic chemotherapy and radiation therapy for patients with locally advanced carcinoma of the cervix. After an initial randomized trial indicated that hydroxyurea was superior to placebo, subsequent studies have evaluated whether the hypoxic sensitizer, misonidazole, or the combination of cisplatin with infusional 5-fluorouracil were superior to hydroxyurea. Other studies have evaluated concurrent chemotherapy with extended field radiation for patients with metastatic disease in their paraaortic nodes. The GOG will continue to attempt to identify and develop superior adjuncts to radiation therapy for this patient population. PMID- 8431909 TI - Integrating radiation therapy into the management of ovarian cancer. AB - Several studies during the last 15 years have elucidated the role of postoperative external beam radiation therapy as curative management of some subsets of patients with ovarian cancer. Despite this, the use of radiation therapy in patients with ovarian cancer has remained a controversial subject. Substantially improved cure rates have not been realized during the past decade despite the early promise of high response rates to cisplatin chemotherapy. Thus, it is important that all currently effective therapies be used for maximum therapeutic gain. This article will review the evidence that radiation therapy is curative in ovarian cancer and highlight the criteria, including stage and grade of disease and tumor residuum, by which patients suitable for such therapy are selected. The rationale for the use of whole abdominopelvic irradiation rather than pelvic or lower abdominal treatment will be discussed, as will the optimal radiation technique and its attendant morbidity. Limited data pertinent to the controversy over the use of radiation therapy versus chemotherapy in early disease, will be reviewed. The possible benefits of consolidation abdominopelvic radiation therapy after chemotherapy in highly selected patients with well differentiated microscopic residual disease at second-look laparotomy or with no residual disease but high a risk for relapse will be considered. PMID- 8431910 TI - Translocation (X;1) in papillary renal cell carcinoma. A new cytogenetic subtype. AB - We report a consistent t(X;1)(p11.2;q21) that was observed in four cases of papillary renal tumors. In one of the cases, two cells showed the cytogenetic abnormality as the only change, whereas the other cases showed additional chromosomal anomalies particularly involving chromosomes 7 and 17. One identical t(X;1) has been reported previously in a papillary renal cell carcinoma. To date, all of the patients carrying this translocation have been males. PMID- 8431911 TI - Analysis of karyotype, SCE, and point mutation of RAS oncogene in Indian MDS patients. AB - Thirty Indian patients diagnosed as having primary myelodysplastic syndrome as per the French-American-British classification were investigated, on admission, for the frequencies of nonrandom karyotype abnormalities, sister chromatid exchange, and point mutations of the RAS oncogene. Successful karyotype analysis was possible in 24 patients, of whom 9 (37.5%) showed nonrandom karyotypic changes. Anomalies of chromosomes 5, 7, and 8 were detected in their bone marrow (BM). In addition, two new anomalies, del(8)(q22) and +19, were observed for the first time in our series. Six MDS patients were studied for SCE in either BM or peripheral blood. These data revealed a normal SCE incidence. Of the 10 MDS patients studied for point mutations of NRAS 12 and 61 and KRAS 12 and 61, one patient exhibited a base substitution at position 1 of the 12th codon of the KRAS gene. These data, gathered for the first time on the Indian patients, throw some light on the nature of genetic changes in MDS of our country. PMID- 8431912 TI - Clonal chromosomal aberrations in a leiomyosarcoma of the sinonasal tract. AB - We report the first cytogenetic analysis of a leiomyosarcoma of the sinonasal tract, a rare neoplasm. Karyotypic analysis showed near-triploid and near tetraploid modal chromosome numbers with extensive structural and numerical aberrations. Three consistent structural changes, including i(6p), der(10)ins(10;1)(q26;q23q44), and der(12)t(1;12)(q11;q24) were observed in most cells. A der(11)t(11;?)(p15;?) was observed in 14 of 20 cells. Clonal structural rearrangements, including i(1q), del(2)(q37), der(3)t(3;?)(p25;?), del(4)(q31), del(7)(q32), der(12)t(12;?)(p12;?), der(15), del(21)(q22), and der(X) were each observed in a few cells. Numerical changes, including trisomies for chromosomes 2 5, 7, 9, 11, 15, 17, 18, and 20 and monosomies 10 and 12 were observed. Comparison of our findings to those of leiomyosarcomas at different sites showed trisomies 7 and 20 and rearrangements of 11p12-p15 and 21q22. PMID- 8431913 TI - Clinical detection of BCR-abl fusion by in situ hybridization in chronic myelogenous leukemia. AB - We describe the use of the fluorescence in situ hybridization (FISH) technique to detect residual Philadelphia chromosome-positive (Ph+) cells in a patient with blastic phase chronic myelogenous leukemia (CML) after aggressive cytoreductive treatment. The analysis was made in interphase nuclei because of the very small number of recognizable metaphases in leukemic patients. FISH was a reliable tool for the detection of chromosome translocations in interphase nuclei as compared with conventional cytogenetic and polymerase chain reaction (PCR) techniques. PMID- 8431914 TI - Cytogenetic findings in 111 ovarian cancer patients: therapy-related chromosome aberrations and heterochromatic variants. AB - The chromosomes of 111 ovarian cancer patients were studied in G- and C-banded slides from peripheral blood lymphocyte (PBL) cultures for chromosome damage caused by chemotherapy and radiotherapy and for asymmetry of the constitutive heterochromatin of chromosomes 1, 9, and 16. We also monitored the survival of these patients to determine whether any secondary neoplasia induced by the therapy and report the findings of our investigations. Melphalan (MEL) was the only drug used in single-drug chemotherapy. The incidence of chromosome abnormalities in melphalan-treated cells (25%) was higher than in the control group (17%). The incidence of structural changes was also higher (10.5%) in the MEL-treated group than in controls (6%). After treatments with combinations of drugs, the incidence of structural changes remained at the same level (11%). In the patients receiving combined treatment with MEL and radiation, the rate of structural changes increased dramatically (24%). The overall rate of chromosome aberrations in this group was also higher (50%). Combination of two or more drugs and radiation produced only 14% structural chromosome changes. The overall rate of chromosome aberrations was also low (20%) in this group. Of 111 patients studied, only 33 were alive 6 years after initiation of the study. Of the surviving patients, eight had rearranged chromosomes in the first analysis. After 5 years, new blood samples were collected from these patients and chromosome analyses showed abnormal karyotypes in all eight patients. All chromosome abnormalities in the second analysis were completely unrelated to those in the first analysis, however. Whether the chromosome changes in the second analysis were due to therapy or to other unknown factors could not be determined. Data on C-banding and the distribution of inversions indicated that 91% of the patients had C-band heteromorphisms of chromosomes 1, 91% had heteromorphisms of chromosome 9, and 69% had heteromorphisms of chromosome 16. Furthermore, inversions were observed in chromosome 1 (41% of patients), chromosome 9 (28% of patients), and chromosome 16 (5% of patients). PMID- 8431915 TI - Chromosome abnormalities in bone marrow of Fanconi anemia patients. AB - We report the clonal chromosome abnormalities of five patients with Fanconi anemia (FA). In one with myelodysplastic syndrome (MDS), an abnormal clone was present in the bone marrow (BM): 47,XY,trp(1)(q32q44), + mar. Two had acute myeloblastic leukemia (AML), one with monosomy 7 and the other with 46,XY,add(1)(p34),del(7)(p13). In the two others without signs of MDS or AML, pseudodiploidy with 46,XX,-5, +8 and 46,XX, +5, -21 were present, respectively. The significance of these abnormalities is discussed. PMID- 8431916 TI - Consistent interstitial chromosomal deletions in myeloid malignancies and their correlation with fragile sites. AB - Chromosomal deletions occurring in myeloid malignancies have sometimes been reported either with no breakpoints or as terminal deletions. It is of importance to deduce whether these deletions are actually terminal or interstitial because this has implications for their biologic consequences and the mechanism of their development. Chromosomal deletions have been observed in 38 patients with myeloid malignancies. Two or more deletions occurred in six cases, and in seven cases this was part of a complex abnormality. In all, 45 deletions were observed. In all cases analyzed, the deletions consistently were interstitial. Of the 38 cases, 16 were myelodysplastic syndromes (MDS) [refractory anemia (RA), three; RA with ringed sideroblasts (RARS) three; RA with excess of blasts (RAEB) eight; RAEB in transformation (RAEB-t) one; and unclassified, one], 11 cases were acute nonlymphocytic leukemia (ANLL), and 11 were other myeloproliferative disorders [polycythemia rubra vera (PRV) seven; essential thrombocytopenia (ET), three; unclassified, one]. In general, no uniformity of breakpoints could be identified other than del(9)(q13q22.2) most of which occurred with t(8;21) and del(20)(q11.2q13.3 or 13.1). The breakpoints corresponded to or were adjacent to fragile sites in 49% (proximal 64%, distal 33%). These data emphasize that chromosomal deletions in myeloid malignancies are interstitial. The uniformity of breakpoints in del 9q and del 20q supports the concept that in some instances the exact breakpoints may be important through juxtaposition of genes rather than loss of critical regions. The data also suggest that there may be different mechanisms for the development of proximal and distal breakpoints. PMID- 8431917 TI - A method for recovery of high-molecular-weight DNA suitable for field-inversion gel electrophoresis from frozen tumor cells. AB - We describe a simple method for isolation of high-molecular-weight (high-mol-wt, > 800 kilobases) DNA from tumor cell lines frozen without dimethylsulfoxide (DMSO) or other protective agents. This method should be applicable to most frozen tissues and useful for molecular genetic studies such as field-inversion gel electrophoresis (FIGE), or cloning procedures that require access to intact, high-mol-wt DNA. PMID- 8431918 TI - t(5;12)(q31;p12). A clinical entity with features of both myeloid leukemia and chronic myelomonocytic leukemia. AB - We report two patients with a myeloproliferative disorder (Philadelphia chromosome-negative chronic myeloid leukemia) and t(5;12)(q31;p12). Until now, only three cases of a translocation (5;12)(q31;p12) have been reported. All investigators had problems classifying their patient's disease into one of the well-defined entities of either MPD or myelodysplastic disorders. We postulate that this translocation may represent a subgroup of patients with features of both chronic myeloid leukemia and chronic myelomonocytic leukemia (CMMoL). PMID- 8431919 TI - Translocation (8;13) and T-cell lymphoma. A case report. AB - A patient with a myeloproliferative disorder is described with an eosinophilia together with T-cell lymphoma. A unique translocation t(8;13)(p11.2;q12) was present in all bone marrow cells examined at presentation. No evidence of this translocation was found in a peripheral blood lymphocyte culture. Chromosome analysis after 9 months revealed this same translocation as well as an extra chromosome 21 in all cells; 4.5% of cells also had an additional chromosome 9. The morphologic diagnosis at this stage was chronic myelomonocytic leukemia. Immunophenotyping 3 months later was consistent with a stem-cell leukemia. PMID- 8431920 TI - Near-octaploidy in essential thrombocythemia. AB - We report a case of essential thrombocythemia which on cytogenetic analysis showed an abnormal clone with near-octaploidy. Such hyperploidy is extremely unusual in clonal hematologic abnormalities. The possible significance of this finding is discussed. PMID- 8431921 TI - Translocation (12;14)(q13;q32) in myelodysplastic syndrome. AB - We report a patient diagnosed with refractory anemia with excess blasts in transformation (RAEB-t) who underwent an evolution to a nonlymphocytic acute leukemia (ANLL-M5a). Initial cytogenetic study showed a diploid karyotype; however, when ANLL-M5a was diagnosed, the bone marrow (BM) cells showed a t(12;14)(q13;q32), which to our knowledge has not been described previously in a myelodysplastic syndrome (MDS). PMID- 8431922 TI - Isochromosome 1q as the sole karyotypic abnormality in a Sertoli cell tumor of the ovary. AB - Sertoli cell tumors are rare low-grade malignancies occurring in the testis and the ovary. No chromosome studies of this tumor type have yet been reported. We observed an extra i(1q) as the sole chromosome anomaly in an ovarian Sertoli cell tumor. PMID- 8431923 TI - Chromosomal rearrangement, t(12;22)(p13;q13), in acute myelomegakaryoblastic leukemia. PMID- 8431924 TI - Regional chemotherapy for malignant melanoma. PMID- 8431925 TI - Chemotherapy of carcinoma of the stomach. PMID- 8431926 TI - Clinical and preclinical activity of 2',2'-difluorodeoxycytidine (gemcitabine). PMID- 8431927 TI - Strategies for prevention of anthracycline cardiotoxicity. PMID- 8431928 TI - Osteoclast inhibition for the treatment of bone metastases. PMID- 8431929 TI - Knowledge in cancer beliefs: obstacles to care? PMID- 8431930 TI - Syntheses of modified 2-chloro-4-nitrophenyl beta-maltopentaosides as useful substrates for assay of human alpha amylase. AB - Twenty-three novel 2-chloro-4-nitrophenyl beta-D-maltopentaosides modified at the 6(5) and/or 4(5) position were synthesized as substrates for human alpha amylase. Two human alpha amylases hydrolyzed 6(5)-deoxy-6(5)-, 6(5)-O-, and 4(5),6(5)-di-O substituted derivatives at essentially a single D-glucosidic linkage, but 4(5),6(5)-O-bridged and 4(5)-O-substituted derivatives were hydrolyzed at two or more linkages. The amylases displayed smaller Km values for the compounds having hydrophobic modifications. In these derivatives, 2-chloro-4-nitrophenyl O-(6 bromo-6-deoxy-alpha-D-glucopyranosyl)-(1-->4)-tris[O-alpha-D- glucopyranosyl-(1- >4)]-beta-D-glucopyranoside (10), 2-chloro-4-nitrophenyl O-(6-azido-6-deoxy-alpha D-glucopyranosyl)-(1-->4)- tris[O-alpha-D-glucopyranosyl-(1-->4)]-beta-D glucopyranoside (19), and 2-chloro-4-nitrophenyl O-[6-O-(N-isopropyl)carbamoyl alpha-D-glucopyranosyl]-(1-->4)- tris[O-alpha-D-glucopyranosyl-(1-->4)]-beta-D glucopyranoside (30), which were rapidly hydrolyzed by the two amylases at a limited position at an approximately equal rate, were shown to be very useful blocked-type substrates for assay of human alpha amylase. PMID- 8431931 TI - Synthesis of a selectively protected trisaccharide building block that is part of xylose-containing carbohydrate chains from N-glycoproteins. AB - The synthesis is reported of ethyl 4-O-[3-O-allyl-4,6-O-isopropylidene-2-O-(2,3,4 tri-O-acetyl-beta-D- xylopyranosyl)-beta-D-mannopyranosyl]-3,6-di-O-benzyl-2 deoxy-2-phthalim ido-1 - thio-beta-D-glucopyranoside (16), a key intermediate in the synthesis of xylose-containing carbohydrate chains from N-glycoproteins. Condensation of ethyl 3,6-di-O-benzyl-2-deoxy-2-phthalimido-1-thio-beta-D- glucopyranoside (5) with 2,4,6-tri-O-acetyl-3-O-allyl-alpha-D-glucopyranosyl bromide, using silver triflate as a promoter, gave the beta-linked disaccharide derivative 8 (84%). O-Deacetylation of 8 and then isopropylidenation afforded 10, which was converted via oxidation-reduction into ethyl 4-O-(3-O-allyl-4,6-O isopropylidene-beta-D-mannopyranosyl)-3,6-di-O-benz yl-2- deoxy-2-phthalimido-1 thio-beta-D-glucopyranoside (12). Silver triflate-promoted condensation of 12 with 2,3,4-tri-O-acetyl-alpha-D-xylopyranosyl bromide gave 16 (71%). The Xylp unit in 16 and in de-isopropylidenated 16 (17) existed in the 1C4(D) conformation, but that in O-deacetylated 17 (18) existed in the 4C1(D) conformation. PMID- 8431932 TI - Synthesis of 5-deoxy-5-fluoro- and 5-deoxy-5,5-difluoro-netilmicin. AB - 5-Deoxy-5-fluoro- (9) and 5-deoxy-5,5-difluoro-netilmicin (27) have been prepared from the corresponding 5-epi and 5-oxo derivatives of netilmicin by treatment with DAST. Structures of the fluorinated by-products (10, 11, and 12) obtained in one of the synthesis of 9 were determined. 5-Epi-netilmicin (13) and 5-epi-6'-N methyl-netilmicin (21) have also been prepared. PMID- 8431933 TI - Syntheses of subtractively modified 2-chloro-4-nitrophenyl beta-maltopentaosides and their application to the differential assay of human alpha-amylases. AB - Three novel maltopentaosides, 2-chloro-4-nitrophenyl O-(6-deoxy-alpha-D-xylo-hex 5-enopyranosyl)-(1-->4)-tris[O-alpha-D - glucopyranosyl-(1-->4)]-beta-D glucopyranoside (3), 2-chloro-4-nitrophenyl O-(6-deoxy-alpha-D-glucopyranosyl)-(1 ->4)-tris[O- alpha-D-glucopyranosyl-(1-->4)]-beta-D-glucopyranoside (10), and 2 chloro-4-nitrophenyl O-(3,6-anhydro-alpha-D-glucopyranosyl)-(1-->4)-tris[O-alpha D-glucopyran osyl- (1-->4)]-beta-D-glucopyranoside (26) were synthesized by chemical and enzymatic reactions. Two human alpha-amylases, salivary alpha amylase (HSA) and pancreatic alpha-amylase (HPA), hydrolyzed 3 and 10 with the same specificity, almost entirely at a single D-glucosidic linkage, but had no hydrolytic activity for 26. Compound 3 was hydrolyzed by each of these amylases at an approximately equal rate, while 10 was hydrolyzed by HSA 4-fold faster than by HPA. Taking advantage of the difference in the hydrolytic rate of 10, we developed a new method for the differential assay of these two human alpha amylases. PMID- 8431934 TI - Synthesis of alpha,alpha-trehalose 2,3- and 2,3'-diesters with palmitic and stearic acid: potential immunoreactants for the serodiagnosis of tuberculosis. AB - Regioselective monoacylation, by the stannylation method, of 4,6:4',6'-di-O benzylidene-alpha,alpha-trehalose with palmitoyl or stearoyl chloride afforded the 2-palmitate and 2-stearate of the diacetal, whereas partial diacylation led to the corresponding 2,3'-dipalmitate and 2,3'-distearate. Protection of the monoesters in the 2',3' positions by cyclizing silylation with 1,3-dichloro 1,1,3,3-tetraisopropyldisiloxane, followed by acylation of the silyl ethers, gave the fully protected 2,3-dipalmitate, 2,3-distearate, and 2-palmitate-3-stearate. Small proportions of other isomers and triesters were also produced in these reactions. Desilylation and debenzylidenation of the diesters finally furnished 2,3- and 2,3'-di-O-palmitoyl-2,3- and 2,3'-di-O-stearoyl-, and 2-O-palmitoyl-3-O stearoyl-alpha,alpha-trehalose. PMID- 8431935 TI - Determination of the structures of cystocarpic carrageenans from Gigartina skottsbergii by methylation analysis and NMR spectroscopy. AB - The combined use of methylation analysis and high-field 1H and 13C NMR spectroscopy allows the determination of the fine structure of the carrageenans produced by the cystocarpic stage of Gigartina skottsbergii. PMID- 8431936 TI - The gum exudate of Encephalartos longifolius Lehm. (female): further hydrolytic studies. AB - Sequential, acid hydrolysis of the gum exudate from Encephalartos longifolius cones gave the neutral disaccharides beta-Gal-(1-->3)-Ara (1), beta-Gal-(1-->3) Gal, and beta-Gal-(1-->6)-Gal; the triouronic acid beta-GlcA-(1-->6)-beta-Gal-(1- >3)-Ara (2); and the biouronic acids described earlier, namely, beta-GlcA-(1-->6) Gal (3), beta-4-O-MeGlcA-(1-->6)-Gal, and beta-GlcA-(1-->2)-Man (4). Oligomers up to the tetramer of beta-GlcA-(1-->2)-Man alpha-linked through O-4 of GlcA characterised the inner, core region of the complex acidic polysaccharide. Alternating GlcA and Man residues were indicated by FABMS of methylated, acid degraded gum. The presence of the constituent sugar units was confirmed by methylation of the gum and partition chromatography of the products of acid hydrolysis. Partial hydrolysis gave fractions containing terminal and in-chain GlcA attached to Gal and Man. Base-catalysed degradation of the methylated products showed Rha to be exterior to GlcA in the periphery. PMID- 8431937 TI - Alpha-D-glucopyranosyl 1,3-anhydro-beta-D-xylo-hexulofuranoside: an intermediate in the alkaline hydrolysis of alpha-D-glucopyranosyl 3,4-anhydro-beta-D-lyxo hexulofuranoside. PMID- 8431938 TI - The use of a synthetic dideoxygenated pentasaccharide as a specific acceptor for N-acetylglucosaminyltransferase-III. PMID- 8431939 TI - A Monte Carlo method for conformational analysis of saccharides. AB - A Metropolis Monte Carlo (MMC) algorithm was applied to explore conformational spaces spanned by the exocyclic dihedral angles of four disaccharides alpha-D Man(1-->3)-alpha-D-Man(1-->O)Me (1), alpha-D-Man(1-->2)-alpha-D-Man(1-->O)Me (2), methyl beta-cellobioside (3), and methyl beta-maltoside (4). The simulation method uses the HSEA force field and randomly samples the conformational space with an automatic preference for low-energy states. In comparison to a systematic grid search, MMC offers a much more convenient and efficient protocol for the computation of ensemble average values of experimentally accessible NMR parameters such as NOE effects or 3J coupling constants. Energy barriers of a few kcal/mol were found to be surmounted easily when running the simulations with the temperature parameter set at room temperature, whereas passing significantly higher barriers required elevated temperature parameters. Ensemble average NOE values were calculated using the MMC technique and a conventional systematic grid search showing that the MMC method adequately samples the conformational spaces of 1-4. Theoretical NOEs derived for global or local minimum conformations are different from ensemble average values, and it is shown that averaged NOEs agree significantly better with experimental data. Ensemble average NOEs for 1 derived from MMC/HSEA, and previously reported MM2CARB and AMBER calculations all showed good agreement with experimental data, with MMC/HSEA giving the closest fit. PMID- 8431940 TI - Preparation, isolation, and characterization of novel heterogeneous branched cyclomalto-oligosaccharides having beta-D-galactosyl residue(s) on the side chain. AB - Transgalactosylated products of branched cyclodextrins (glucosyl-alpha CD, -beta CD, -gamma CD, and maltosyl-alpha CD, -beta CD, -gamma CD) were synthesized by beta-D-galactosidases from Bacillus circulans and Penicillium multicolor using lactose as a donor substrate and branched CDs as acceptors. Eighteen beta-D galactosylated branched CDs were isolated and purified by HPLC. Their structures were elucidated by FABMS and 13C NMR spectroscopies, and methylation analysis. The chromatographic behavior of these novel heterogeneous branched CDs on three HPLC columns of different separation modes was compared. PMID- 8431941 TI - Yeast genetics and the fall of the classical view of meiosis. PMID- 8431942 TI - Nucleosome displacement in transcription. PMID- 8431943 TI - Elimination of self-reactive B lymphocytes proceeds in two stages: arrested development and cell death. AB - In transgenic mice, self-reactive B lymphocytes are eliminated if they encounter membrane-bound self antigens during their development within the bone marrow. We show here that two separate and sequential events, arrested development and cell death, bring about B cell elimination. Developmental arrest is an early outcome of antigen binding in immature B cells, blocks acquisition of adhesion molecules and receptors important for B cell migration and activation, and is rapidly reversible by removal of antigen. Death of the arrested B cells occurs within 1 to 3 days and can be delayed by expression of a bcl-2 transgene, which results in escape of large numbers of self-reactive B cells from the bone marrow but fails to override the developmental arrest. These findings define a novel pathway for B cell elimination, involving an initial stage vulnerable to breakdown in autoimmune disease. PMID- 8431944 TI - Independent domains of the Sdc-3 protein control sex determination and dosage compensation in C. elegans. AB - sdc-3 is an early-acting regulatory gene that controls both sex determination and X chromosome dosage compensation in C. elegans. It is unique among sdc genes in that its sex determination and dosage compensation functions act independently. The molecular analysis reported here demonstrates that separate domains of the Sdc-3 protein control these two developmental processes. Sequence analysis of 16 sdc-3 alleles reveals that the dosage compensation mutations specifically eliminate a pair of zinc finger motifs at the carboxyl terminus of Sdc-3, while the sex determination mutations after a region with limited homology to the ATP binding domain of myosin. Null mutations, which disrupt both processes, abort translation of Sdc-3 prior to both domains. Analysis of site-directed changes confirms the functional significance of the two separate regions in sex determination and dosage compensation and reveals that an additional region, undetected by genetic analysis, is also required for proper dosage compensation. PMID- 8431945 TI - The eyes absent gene: genetic control of cell survival and differentiation in the developing Drosophila eye. AB - The eyes absent (eya) gene is required at an early stage in development of the D. melanogaster compound eye. In eya mutants, progenitor cells in the eye disc undergo programmed cell death anterior to the morphogenetic furrow, rather than proceeding into the pathway of retinal differentiation. A low level of cell death normally occurs at this stage, suggesting that eya activity influences the distribution of cells between differentiation and death. Molecular analysis identifies a nuclear protein expressed in progenitor cells prior to differentiation. Transformation with the cDNA prevents progenitor cell death and allows the events that generate the eye to proceed. eya activity is required for the survival of eye progenitor cells at a critical stage in morphogenesis. PMID- 8431946 TI - CTR1, a negative regulator of the ethylene response pathway in Arabidopsis, encodes a member of the raf family of protein kinases. AB - We isolated a recessive Arabidopsis mutant, ctr1, that constitutively exhibits seedling and adult phenotypes observed in plants treated with the plant hormone ethylene. The ctr1 adult morphology can be phenocopied by treatment of wild-type plants with exogenous ethylene and is due, at least in part, to inhibition of cell elongation. Seedlings and adult ctr1 plants show constitutive expression of ethylene-regulated genes. The epistasis of ctr1 and other ethylene response mutants has defined the position of CTR1 in the ethylene signal transduction pathway. The CTR1 gene has been cloned, and the DNA sequences of four mutant alleles were determined. The gene encodes a putative serine/threonine protein kinase that is most closely related to the Raf protein kinase family. PMID- 8431947 TI - Temperature-sensitive mutations demonstrate roles for yeast fibrillarin in pre rRNA processing, pre-rRNA methylation, and ribosome assembly. AB - We have generated temperature-sensitive lethal point mutations in the small nucleolar RNA-associated protein fibrillarin (encoded by the NOP1 gene in yeast) and analyzed their effects on ribosome synthesis. The five alleles tested all prevent synthesis of normal ribosomes, but in dramatically different ways. At the non-permissive temperature, the nop1.2 and nop1.5 alleles prevent synthesis of both 18S and 25S rRNA and all pre-rRNA species except the 35S primary transcript. In contrast, the nop1.3, nop1.4, and nop1.7 alleles do not strongly impair processing. In nop1.3 strains, nucleolar methylation of pre-rRNA is strongly inhibited; late, cytoplasmic methylation of 18S rRNA and tRNA methylation continue. The nop1.4 and nop1.7 alleles result in the synthesis of cytoplasmic 60S ribosomal subunits with strongly aberrant mobilities on sucrose gradients even at the permissive temperature, owing to the impairment of a late step in ribosome assembly. Thus, all major posttranscriptional activities in ribosome synthesis, pre-rRNA processing, pre-rRNA modification, and ribosome assembly are dependent on fibrillarin. PMID- 8431948 TI - Transcript cleavage factors from E. coli. AB - Two transcription elongation factors (GreA and GreB) related in primary sequence were isolated from E. coli. Each factor induced cleavage of the nascent transcript in artificially halted elongation complexes followed by the loss of the 3' proximal fragment and resumption of elongation from the new 3' terminus. GreA induced cleavages 2 or 3 nt behind the terminus while GreB released longer oligonucleotides up to 9 nt in length. The pattern of cleavages characteristically changed as the transcription complex advanced, supporting the "inchworm" model of RNA polymerase propagation. In addition to attacking artificially halted complexes, both factors antagonized the action of natural elongation-arresting sites that occasionally trap the advancing complex. GreB rescued the arrested complexes via the transcript cleavage and restart pathway while GreA acted by an unknown mechanism, preventing the arrest only if added before the polymerase reached the arresting site. PMID- 8431949 TI - High affinity DNA-binding Myc analogs: recognition by an alpha helix. AB - Myc and other basic-helix-loop-helix-leucine zipper (b-HLH-ZIP) proteins bind the sequence CACGTG. Exhaustive mutagenesis in the basic domain identified four amino acids critical for DNA binding with spacing suggestive of an alpha-helical face. Surprisingly, two highly conserved amino acids were nonessential for DNA binding. Circular dichroism demonstrated a DNA-induced alpha-helical transition. A series of analogs were constructed with multiple simultaneous alanine substitutions at nonessential positions and a critical lysine for arginine substitution. In this way 35-fold higher specific affinity for CACGTG was obtained as compared with the basic domain of c-Myc. These b-HLH-ZIP proteins appear to bind the same palindromic sequence and may compete for common sites in vivo. Additionally, a C terminal basic region clamp motif was identified that was also identifiable in crystal structures from several different families of DNA-binding factors. PMID- 8431950 TI - Identification of a Saccharomyces cerevisiae mutation that allows cells to grow without chitin synthase 1 or 2. AB - Chitin is a component of the yeast cell wall which is localized to the septum between mother and daughter cells. Previous work in Saccharomyces cerevisiae has shown that this organism possesses three chitin synthases, 1, 2, and 3. Disruption experiments have shown that loss of chitin synthase 2 has a more profound effect on cell viability than loss of either of the other two and is lethal in complete media. We report here the finding of an S. cerevisiae strain which does not require the chitin synthase 2 structural gene for viability. We present evidence that there is a gene in this strain which suppresses the lethality of disruption of the chitin synthase 2 structural gene and is genetically distinct from the structural genes for chitin synthase 1 and chitin synthase 2. We show that an S. cerevisiae mutant containing the suppressor and lacking both structural genes for chitin synthase 1 and 2 has normal amounts of chitin in its cell wall. We hypothesize that the suppressor gene encodes or controls the expression of chitin synthase 3. PMID- 8431951 TI - Characterization of the Trichoderma reesei cbh2 promoter. AB - A 613-bp fragment of the 5' upstream region of the Trichoderma reesei cbh2 gene (coding for the cellulolytic enzyme cellobiohydrolase II) has been isolated and sequenced. Fusion of this fragment to the E. coli uidA gene (coding for beta glucuronidase) leads to--albeit low--expression of beta-glucuronidase activity in the presence of cellulose and upon the addition of low molecular weight inducers (sophorose, lactose) of cellobiohydrolase II. It also governed the formation of beta-glucuronidase activity during sporulation and its transport to the conidial surface. However, despite the presence of a signal peptide in the cbh2:uidA fusion, beta-glucuronidase was not secreted in T. reesei. Defined fragments of the 613-bp promoter region were isolated and used to identify areas involved in the regulation of cbh2 expression by protein-DNA binding assays. At least two binding areas--between -443/-363 and -363/-173, respectively--were identified. In both areas, the DNA-protein complex observed was appreciably larger when cell free extracts from sophorose-induced mycelia were used. This suggests that at least one of the proteins regulating cbh2 transcription is itself induced by cellulose. PMID- 8431952 TI - Disruption of the 3' phosphoglycerate kinase (pgk) gene in Aspergillus nidulans. AB - We report the isolation of a pgk- mutant strain of Aspergillus nidulans by means of a gene disruption strategy, and demonstrate that the pgk gene is located on chromosome VIII. The pgk- mutant conidiates poorly, will only grow on media supplemented with both a glycolytic and a gluconeogenic carbon source, and is inhibited by hexoses. PMID- 8431953 TI - Pleiotropic and differential phenotypic expression of two sn (snowflake) mutant alleles of Neurospora crassa: analysis in homokaryotic and heterokaryotic cells. AB - Mutations sn (snowflake) JL301 and C136, in the centromere region of linkage group I in Neurospora crassa, are at 0.6-3.0 map units to the left of the os-4 locus. Strains carrying snJL301 produce very short aerial hyphae and only arthroconidia, and do not grow in high salt media. snC136 strains produce aerial hyphae, with abnormally large and rounded blastoconidia, at the top of the agar slant cultures, and revert to wild-type growth in high salt media. Studies with forced primary heterokaryons indicate that snJL301 is recessive while snC136 is a semi-dominant and gene-dose dependent allele, with respect to the wild-type. Taken together the results show that: (1) the sn mutations are allelic with a differential pleiotropic phenotype, and (2) snC136 may code for a partially functioning gene product while snJL301 appears to be a null allele. PMID- 8431954 TI - Cloning and sequencing of the 3-phosphoglycerate kinase (PGK) gene from Penicillium citrinum and its application to heterologous gene expression. AB - The gene coding for 3-phosphoglycerate kinase (PGK) in ML-236B (compactin) producing Penicillium citrinum was isolated from the recombinant phage lambda library using the corresponding Aspergillus nidulans pgk gene as a probe. The P. citrinum pgk gene has an open reading frame of 1,254 bp, encoding a protein of 417 amino acids with a predicted molecular weight of 44,079 daltons. The position of the two introns, 59 and 60 bp respectively, was deduced from an homology comparison with the sequence of the A. nidulans pgk gene. The PGK protein of P. citrinum shows extensive high homology to the PGKs of four other fungi: P. chrysogenum (93%), A. nidulans (84%), Trichoderma reesei (78%) and Saccharomyces cerevisiae (68%). Almost total conservation is found in P. citrinum of residues thought to be important for the structure and function of the yeast enzyme. The strong codon preference found has greater similarity to that in other filamentous fungi than in yeast. A DNA fragment encompassing the pgk gene was shown to hybridize a 1.35-kb poly(A)+RNA, sufficient to encode the PGK polypeptide. A fused gene, pgk-hpt, containing the putative pgk promoter and the open reading frame of the Escherichia coli hygromycin B phosphotransferase (hpt) gene was constructed, and was successfully used to transform P. citrinum to a hygromycin B (HmB)-resistant phenotype. PMID- 8431955 TI - Titration of replication activity by increasing ARS dosage in yeast plasmids. AB - The rep1 region of the yeast mitochondrial genome, a putative replication origin, contains a weak autonomously replicating sequence (ARS). Nucleotide-sequence and deletion analyses have identified two 11-base pair ARS consensus sequences, numerous near matches to the ARS core, and a region of curvature that may contribute to ARS function. Based on the amplified nature of petite-derivative mitochondrial DNA encompassing this locus, we have constructed plasmids containing an increasing dosage of ARS elements. The rep1 ARS element can have an additive effect on plasmid stability when present either as a tandem dimer or as an unlinked pair. However, the presence of a third ARS copy does not further enhance plasmid stability. These results indicate that measurable dosage effects can be defined only in circumstances where weak ARS elements are employed, and that plasmid maintenance within yeast cells is saturable and varies among the different sequences promoting replication. PMID- 8431956 TI - Characterization of the Brassica campestris mitochondrial gene for subunit six of NADH dehydrogenase: nad6 is present in the mitochondrion of a wide range of flowering plants. AB - We have isolated the Brassica campestris mitochondrial gene nad6, coding for subunit six of NADH dehydrogenase. The deduced amino-acid sequence of this gene shows considerable similarity to mitochondrially encoded NAD6 proteins of other organisms as well as to NAD6 proteins coded for by plant chloroplast DNAs. The B. campestris nad6 gene appears to lack introns and produces an abundant transcript which is comparable in size to a previously described, unidentified transcript (#18) mapped to the B. campestris mitochondrial genome. An alignment of NAD6 proteins (deduced from DNA sequences) suggests that B. campestris nad6 transcripts are edited. Southern-blot hybridization indicates that nad6 is present in the mitochondrial genome of all of a wide range of flowering plant species examined. PMID- 8431957 TI - RNA editing of a chimeric maize mitochondrial gene transcript is sequence specific. AB - RNA editing was analysed in the mitochondrial ATPase complex subunit 6 gene (atp6) transcripts of the C male-sterile cytoplasm (cms-C) of maize. The only copy of atp6 in cms-C, designated C-atp6, is a triple gene fusion product comprised of DNA sequences derived from atp9, atp6, and an unknown origin. Sequences of cDNAs revealed 19 C to U alterations resulting in 16 amino acid residue changes compared to the genomic sequence. The only C to U edit in the 39 nucleotide sequence similar to atp9 was comparable to a change in the complete atp9 mRNAs of Petunia, Oenothera, wheat, and sorghum. The 442 nucleotides of unknown origin were not edited. The 18 editing events within the atp6 homologous region were similar to those in the atp6 transcripts of sorghum. RNA editing in maize C-atp6 transcripts introduces a translational stop codon at the same position where it is created by editing in sorghum and Oenothera atp6 mRNAs and is already present in atp6 open reading frames of most other plant and non-plant organisms. Our results, along with other reports on editing in chimeric transcripts, indicate that RNA editing is not influenced by rearrangements but instead is sequence specific. PMID- 8431958 TI - Structural alterations of the chloroplast genome found in grasses are not common in monocots. AB - The distribution of structural rearrangements of the chloroplast genome found in grass cpDNA in comparison to that of tobacco was systematically checked in the cpDNAs of representative monocots. The physical map of lily cpDNA, which shares a key position in the diversity of monocotyledonous plants, was constructed to assess whether three inversions found in grass cpDNA are common in monocots. Specific probes for the detection of (1) intron loss in the rpoC1 gene, (2) insertional sequence gain in rpoC2, (3) deletion of ORF2280 in the inverted repeats, (4) non-reciprocal translocation of rpl23, and (5) rearrangements of ORF512, were hybridized to cpDNAs of lily, onion, spiderwort, two turf grasses, and wheat. The existence of intervening sequences in the rpoC1 and rpoC2 genes was also confirmed by PCR analysis. All markers used in the study revealed that structural rearrangements of the chloroplast genome were restricted to grasses, indicating that drastic structural alterations of the chloroplast genome had occurred in the ancestor(s) of grasses. These results also suggest that structural analysis of the chloroplast genome is applicable to the phylogenetic reconstruction of related plants. PMID- 8431959 TI - The smt-0 mutation which abolishes mating-type switching in fission yeast is a deletion. AB - Mating-type switching in the fission yeast, S. pombe, is initiated by a DNA double-strand break (DSB) between the mat1 cassette and the H1 homology box. The mat1-cis-acting mutant, smt-0, abolishes mating-type switching and is shown here to be a 263-bp deletion. This deletion starts in the middle of the H1 homology box, 31 bp from the site of the DSB, and extends into the flanking region distal to mat1. The sequence of the region distal to H1 in the wild-type is also presented. In this region we observe a bias in the distribution of purine residues between the two DNA strands. PMID- 8431960 TI - Molecular cloning of the yeast OPI3 gene as a high copy number suppressor of the cho2 mutation. AB - By functional complementation of the auxotrophic requirements for choline of a cdg1, cho2 double-mutant, by transformation with a genomic DNA library in a high copy number plasmid, two different types of complementing DNA inserts were identified. One type of insert was earlier shown to represent the CHO2 structural gene. In this report we describe the molecular and biochemical chemical characterization of the second type of complementing activity. The transcript encoded by the cloned gene was about 1000-nt in length and was regulated in response to the soluble phospholipid precursors, inositol and choline. A gene disruption resulted in no obvious growth phenotype at 23 degrees C or 30 degrees C, but in a lack of growth at 37 degrees C in the presence of monomethylethanolamine. Null-mutants exhibited an inositol-secretion phenotype, indicative of mutations in the lipid biosynthetic pathway. Complementation analysis, biochemical analysis of the phospholipid methylation pathway in vivo, and comparison of the restriction pattern of the cloned gene to published sequences, unequivocally identified the cloned gene as the OPI3 gene, encoding phospholipid-N-methyltransferase in yeast. When present in multiple copies the OPI3 gene efficiently suppresses the phospholipid methylation defect of a cho2 mutation. As a result of impaired synthesis of phosphatidylcholine, the INO1 deregulation phenotype is abolished in cho2 mutants transformed with the OPI3 gene on a high copy number plasmid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431961 TI - Products formed from the in vitro reaction of metabolites of 3-aminochrysene with calf thymus DNA. AB - 3-Aminochrysene, a mutagenic geometric isomer of the mutagenic and carcinogenic aromatic amine 6-aminochrysene, has been synthesized and its metabolic activation studied by characterization of the products formed from the reaction of metabolites with calf thymus DNA. DNA adducts produced by 3-aminochrysene via N oxidation were examined by preparing 3-nitrosochrysene and incubating the nitroso derivative with calf thymus DNA in the presence of ascorbic acid (to generate the N-hydroxy derivative) at pH 5. The major adduct, as determined by 1H-NMR and thermospray-mass spectrometry of the modified nucleoside obtained after enzymatic hydrolysis of the modified DNA, was N-(deoxyguanosin-8-yl)-3-aminochrysene. Thus, the reaction of N-hydroxy-3-aminochrysene with DNA differs from that of N-hydroxy 6-aminochrysene, which had previously been shown to generate N-(deoxyguanosin-8 yl)-6-aminochrysene, 5-(deoxyguanosin-N2-yl)-6-aminochrysene and N-(deoxyinosin-8 yl)-6- aminochrysene as major adducts. 32P-Postlabeling analysis of DNA treated with 3-aminochrysene in the presence of liver microsomes from rats pretreated with phenobarbital indicated an adduct pattern identical to that seen with DNA that had been treated with 3-nitrosochrysene and ascorbic acid. However, DNA treated with 3-aminochrysene (3-AC) in the presence of liver microsomes from rats pretreated with 3-methylcholanthrene contained a major adduct that was chromatographically distinct from N-(deoxyguanosin-8-yl)-3-aminochrysene. PMID- 8431962 TI - Studies of the potency of protein kinase inhibitors on ATPase activities. AB - Tyrosine as well as serine/threonine protein kinase inhibitors have potentially two sites of interaction with their targets: the protein-substrate binding site and the ATP binding site. The latter could be modelized by measuring the capacity of protein kinase inhibitors to inhibit ATPase activities. In order to do so, we assess a novel, highly sensitive HPLC method based on hydrophilic separation of [gamma-32P]ATP and [32P]Pi. The novel assay is presented. Furthermore, the potency of 13 protein kinase inhibitors was tested on two types of ATPase, namely: apyrase and partially purified liver mitochondria F1-ATPase. The method described for the assay of ATPase can be used with almost any type of enzyme catalyzing this activity. Only cibacron blue and suramin show interesting capacities in inhibiting these ATPase activities pointing out that several widely used protein kinase inhibitors are at least somewhat specific in that they do not inhibit these two ATPases. PMID- 8431963 TI - Mass spectrometric investigation of the presence of 7-methyl ring-opened guanine derivatives in urine. AB - The involvement of chemical alkylating agents in tumorigenesis and chemotherapy is well established and it was shown that one of the main sites of alkylation is the N-7 of guanine in DNA. Though excision of damaged bases is regarded as one of the repair mechanisms in damaged DNA there is a scarcity of information concerning the excised final metabolites in body fluids. This study attempts to demonstrate the usefulness of CAD MS/MS for the detection of the final metabolite deformylated ring-opened 7 alkylguanine in urine. Such mass spectrometric methods can be used in biomedical studies. PMID- 8431964 TI - Mutagenicity of formaldehyde in Chinese hamster lung fibroblasts: synergy with ionizing radiation and N-nitroso-N-methylurea. AB - Cultured Chinese hamster V79 cells, a widely utilized model system in risk assessment of environmental agents, have been utilized to measure toxicity and mutagenicity of formaldehyde with or without previous exposure to either the alkylating agent N-nitroso-N-methylurea or to ionizing radiation. Each of these agents caused a dose-dependent decrease in colony forming efficiency and a parallel increase in 6-thioguanine resistant colonies. Significant mutant frequencies were induced by 0.3 up to 1 mM formaldehyde, 2 and 4 Gy of radiation and 0.2 and 0.5 mM N-nitroso-N-methylurea. Exposure of cells to ionizing radiation or N-nitroso-N-methylurea followed by submutagenic concentrations of formaldehyde potentiated both the cytotoxicity and the mutagenicity as compared with the corresponding separate effects caused by each of these agents. Taken together, these studies clearly demonstrate genotoxic effects in vitro of three recognized carcinogens, i.e. formaldehyde, N-nitroso-N-methylurea and ionizing radiation. Moreover, the synergies now demonstrated in regards to cytopathic consequences indicate interactive effects between formaldehyde and these agents, representing both a chemical and a physical carcinogen. PMID- 8431965 TI - Effects of acute sodium arsenite administration on the pulmonary chemical metabolizing enzymes, cytochrome P-450 monooxygenase, NAD(P)H:quinone acceptor oxidoreductase and glutathione S-transferase in guinea pig: comparison with effects in liver and kidney. AB - Tissue specific changes in the cytochrome P-450 (P-450) monooxygenase system were observed following a single subcutaneous dose of sodium arsenite (75 mumol/kg), a known inducer of stress proteins. P-450 monooxygenase activities were assayed with several isozyme selective substrates; 7-ethoxyresorufin, 7-pentoxyresorufin, 4-aminobiphenyl and erythromycin. Both tissue selective and isozyme selective changes in monooxygenase activity were noted. For example, the rate of 4 aminobiphenyl N-hydroxylation (ABH) was increased by arsenite administration in lung but not in liver. Arsenite inhibited 7-ethoxyresorufin O-deethylation (ERF) in all tissues of control animals, but to a lesser extent in lung. However, increases of ERF activity occurred after arsenite treatment in lung of beta naphthoflavone (beta NF)-treated guinea pigs whereas arsenite decreased ERF activities in the kidney and liver of these animals. These complex effects on ERF activity may in part be modulated by induction of heme oxygenase, whose activity was increased 2.5-3.5-fold in these organs by arsenite. The highest heme oxygenase activity was found in kidney with lower activities being present in liver and lung, respectively. These data are consistent with the decreased P-450 content observed in kidney and liver microsomes of arsenite treated guinea pigs. On the other hand there was either no change or a slight increase (about 2-fold) in the pulmonary microsomal P-450 content of these animals. A complex pattern of induction for the non-heme, Ah locus associated enzyme, NAD(P)H:quinone acceptor oxidoreductase (QOR) was also observed. With menadione as substrate arsenite treatment increased QOR activity in all tissues studied. However, with dichlorophenolindophenol (DCPIP) as substrate a significant arsenite effect was observed only in the kidney. Significant differences between the QOR substrates were also observed in beta NF-treated guinea pigs and control animals. Our results are consistent with the presence of more than one form of QOR in the guinea pig. Arsenite treatment also caused an increase in glutathione S transferase activity, with 2,4-dinitro-1-chlorobenzene (DNCB) as substrate, of guinea pig kidney but not liver or lung. PMID- 8431966 TI - Prevention of singlet oxygen-induced DNA damage by lipoate. AB - Among the several biologically and pharmacologically active sulfur compounds examined, only lipoic acid and dihydrolipoic acid provided protection to plasmid DNA against singlet molecular oxygen (1O2). 1O2 was generated in phosphate buffer by the thermal dissociation of the endoperoxide of 3,3'-(1,4-naphthylidene) dipropionate (NDPO2). The protecting effect of lipoic acid was time- and pH dependent and significant protection was seen even at 50 microM. The antioxidant effect was adversely affected by temperatures above 45 degrees C. Superoxide dismutase and catalase marginally enhanced this effect. Metal chelation with EDTA decreased the protection by lipoate, indicating that metal ions may be involved. The protective effect was diminished when the disulfide was added after single strand breaks were induced by 1O2. The formation of 8-oxoguanosine from guanosine upon exposure to NDPO2 was not altered by lipoate. PMID- 8431967 TI - Modulation of drug cytotoxicity in wild-type and multidrug-resistant tumor cells by stereoisomeric series of C-20'-vinblastine congeners that lack antimicrotubule activity. AB - Seven binary vinca alkaloid congeners were newly synthesized as the C14' or C16'(20') or C14'16'(20') stereoisomers of C20'-modified VBL. These congeners lacked detectable antimicrotubule activity in assays of polymerization of purified microtubule protein and of mitotic arrest induction. The compounds modulated the cytotoxicity of VBL, VCR, and DOX in sarcoma and colon-tumor cell lines. In wild-type cell lines, each congener elicited a concentration-dependent enhancement of cytotoxicity that was drug- and cell-type-selective. For example, C20'-deoxy C14'16'20'-epi VBL sensitized sarcoma S180 cells 19-fold to DOX and 11 fold to VCR but had no effect on VBL cytotoxicity. In the rat colon-cancer cell lines there was preferential enhancement of VCR cytotoxicity by most congeners. In two MDR cell strains of S180, the modulation potency of each congener was independent of specific drug or of resistance level. As a result, the amount of modulator (concentration) required for reversal was proportional to the drug resistance level. Such properties were not displayed by the monomeric vinca alkaloid modulator vindoline. The potency of drug modulation in both wild-type and MDR cells strains was dependent on the stereoisomeric form of the congener and its C20'-substituents. PMID- 8431968 TI - Pharmacokinetics of etoposide: correlation of pharmacokinetic parameters with clinical conditions. AB - The pharmacokinetic parameters of etoposide were established in 35 patients receiving the drug parenterally within the framework of different polychemotherapy protocols. A total of 62 data for 24-h kinetics were analysed. After sample extraction and high-performance liquid chromatography (HPLC) or thin layer chromatographic (TLC) separation, etoposide was measured by means of [252Cf]-plasma desorption mass spectrometry (PDMS). This highly specific detection system proved to be very practicable and reproducible. The present study comprised two parts that were absolutely comparable in terms of clinical and pharmacokinetic parameters. In part II of the study, sensitivity was improved by modifying the analytical technique. After the exclusion of patients who had previously been given cisplatin or who exhibited renal impairment and of one patient who showed extremely high levels of alkaline phosphatase, gamma-GT and SGPT, the mean values calculated for the pharmacokinetic parameters evaluated were: beta-elimination half-life (t 1/2 beta), 4.9 +/- 1.2 h; mean residence time (MRT), 6.7 +/- 1.4 h; area under the concentration-time curve (AUC), 5.43 +/- 1.74 mg min ml-1; volume of distribution at steady state (Vdss), 6.8 +/- 2.7 l/m2; and clearance (Cl), 18.8 +/- 5.3 ml min-1 m-2. The pharmacokinetic parameters were correlated with 12 different demographic or biochemical conditions. Impaired renal function, previous application of cisplatin and the age of patients were found to influence etoposide disposition to a statistically significant extent. We suggest that the dose of etoposide should be reduced in elderly patients and/or in individuals with impaired renal function, especially in those exhibiting general risk factors such as reduced liver function with regard to the polychemotherapy. PMID- 8431969 TI - Phase I study using desferrioxamine and iron sorbitol citrate in an attempt to modulate the iron status of tumor cells to enhance doxorubicin activity. AB - A novel approach to enhance the activity of doxorubicin is to increase the availability of cellular "chelatable" iron to participate in doxorubicin-mediated free-radical generation. To achieve this, we designed a regimen consisting of desferrioxamine (DFO, 50 mg/kg daily given as an i.v. infusion over 72 h) to increase cellular iron uptake. Thereafter, the combination of iron sorbitol citrate (ISC) and doxorubicin (as a single agent or as part of the CHOP regimen) was given. In a phase I study we investigated the toxicity of this regimen in nine patients with refractory malignant disease. Severe but reversible ocular toxicity (i.e., acute maculopathy) was observed in two patients. As these patients were the only ones who were pretreated with cisplatin, we caution against the use of DFO in cisplatin-pretreated patients. Severe phlebitis was encountered in five of nine patients. A partial remission was observed in two of four patients with refractory Non-Hodgkin's lymphoma who were treated with DFO, ISC, and doxorubicin as part of the CHOP regimen. We conclude that pretreatment with DFO and iron sorbitol citrate may be of benefit in the treatment of malignancies with doxorubicin-containing regimens, but ocular toxicity and severe phlebitis limits the use of DFO in this approach. The attachment of DFO to biocompatible polymers may be a method of overcoming the observed toxicity and warrants further study. PMID- 8431970 TI - Effects of verapamil on the pharmacokinetics and metabolism of epirubicin. AB - Experimental data suggest that multidrug resistance in cancer may be overcome by using an increased dose of anticancer agent(s) in combination with a resistance modifying agent (RMA). We studied the pharmacokinetics and metabolism of both epirubicin (EPI) and verapamil (VPL) to explore the possible pharmacokinetic interactions between these two drugs. Ten patients with advanced breast cancer were given EPI (40 mg/m2 in a daily i.v. bolus for 3 consecutive days), and five of them also received VPL (4 x 120 mg/daily p.o. for 4 consecutive days). The data indicated a significant interaction between these two drugs that affected their metabolism. The areas under the concentration-time curves (AUC) obtained for epirubicin glucuronide, epirubicinol glucuronide, and both of the 7-deoxy aglycones were higher in the EPI + VPL group as compared with the EPI group. The AUC, terminal half-life, mean residence time, volume of distribution at steady state, and plasma clearance of EPI alone as compared with EPI + VPL did not differ significantly. These results suggest either an induction of enzymes necessary for drug metabolism or an increase in the liver blood flow, resulting in an enhanced generation of metabolites with time or in an inhibition of excretion processes. Comparisons of the AUC values obtained for EPI and its metabolites after the first, second, and third injections of EPI revealed a cumulative effect for the metabolites that was more pronounced in the EPI + VPL group, being significant (P < 0.05) for epirubicin glucuronide in both treatment groups and for epirubicinol glucuronide in the EPI + VPL group. Maximal concentrations of VPL and nor-VPL reached 705 +/- 473 and 308 +/- 122 ng/ml, respectively, with the steady-state concentrations being 265 +/- 42 ng/ml for VPL and 180 +/- 12 ng/ml for nor-VPL. PMID- 8431971 TI - Development of a model of melphalan-induced gastrointestinal toxicity in mice. AB - The tolerated dose of melphalan is limited by bone marrow suppression; when this complication is ameliorated by bone marrow transplantation, the dose-limiting toxicity becomes gastrointestinal mucositis. No intervention to date has been successful in modulating this life-threatening complication of melphalan. We conducted studies to develop a murine model of melphalan-induced gastrointestinal toxicity to facilitate the preclinical identification of effective strategies for reducing this toxicity. Melphalan given at the 90% lethal dosage produced severe gastrointestinal mucositis and mortality (13 of 23 treated mice). Syngeneic bone marrow transplantation, effective in preventing the myeloablation produced by total-body irradiation, was ineffective in preventing melphalan-induced mortality (16 of 23 treated mice), indicating that gastrointestinal mucositis was the dose limiting toxicity. On the basis of the results of previous studies, which revealed that depletion of glutathione enhances the antineoplastic activity of melphalan and that glutathione is required for murine intestinal function, we attempted to modulate melphalan-induced gastrointestinal toxicity by the administration of glutathione (8-10 mmol/kg given in 1 ml sterile water by gavage at 12-h intervals for 4-8 doses). Glutathione therapy failed to produce a significant increase in mucosal glutathione content in animals treated with melphalan plus glutathione gavage as compared with those receiving melphalan alone (P > 0.05), and histologic mucosal injury secondary to melphalan was not reduced. The administration of glutathione in the presence or absence of concomitant bone marrow transplantation did not decrease melphalan-induced mortality (melphalan alone, 16/26 deaths; melphalan plus glutathione, 14/25 deaths; melphalan plus glutathione plus bone marrow transplantation, 20/26 deaths). Studies using a reduced melphalan dose (50% lethal dosage) produced similar results, with no survival benefit being seen following glutathione administration. Our studies suggest that melphalan-induced mucositis can be studied in a mouse model in which this complication is dose-limiting. Although glutathione administration at the dose and schedules initially studied is not effective in reducing this damage, other therapeutic strategies such as the use of alternative glutathione regimens or other thiols can be effectively studied in this system. PMID- 8431972 TI - Cytotoxicity, DNA cross-linking, and DNA single-strand breaks induced by cyclophosphamide in a rat leukemia in vivo. AB - A study of cyclophosphamide (CP)-induced DNA damage and repair occurring in vivo was conducted in the brown Norway rat myelocytic leukemia (BNML) model. DNA single-strand breaks (SSB), DNA-DNA interstrand cross-links (DIC), DNA-protein cross-links (DPC), and DNA double-strand breaks (DSB) were measured by alkaline and neutral elution. After i.p. injection of 50 mg/kg CP, DIC were detectable at 1 h and peaked at 8 h. DPC were detectable at 2 h and peaked at 6 h. Both DIC and DPC persisted at a relatively high level until 28 h. Dose-response curves for both DIC and DPC were determined at 4 h after CP injection over the dose range of 25-150 mg/kg. These doses ranged from the minimally effective dose to doses curative for rats bearing this leukemia (1- to 9-log kill of leukemia cells). No SSB or DSB was observed at 4 h after CP injection over the dose range of 15-250 mg/kg, but a low level of SSB was observed at 18-28 h after CP treatment. These data suggest that the cytotoxic effect of CP in vivo is mediated mostly by DIC and DPC. SSB appearing late after CP injection in vivo may be a reflection of repair of DIC and DPC and an indication of the optimal timing for administration of DNA-repair inhibitors. This observation is of interest since our earlier work demonstrated that hydroxyurea can potentiate the therapeutic benefit of CP in this model when it is given over the 4-day period immediately after CP treatment. PMID- 8431973 TI - Determination of the urinary excretion of ifosfamide and its phosphorated metabolites by phosphorus-31 nuclear magnetic resonance spectroscopy. AB - Phosphorus-31 nuclear magnetic resonance spectroscopy was used to analyze urine samples obtained from patients treated with ifosfamide (IF). This technique allows the individual assay of all phosphorated metabolites of IF in a single analysis without the need for prior extraction. In addition to the classic IF metabolites 2-dechloroethylifosfamide (2DEC1IF), 3-dechloroethylifosfamide (3DEC1IF), carboxyifosfamide (CARBOXYIF), and isophosphoramide mustard (IPM), several signals corresponding to unknown phosphorated compounds were observed. Four of them were identified: one is alcoifosfamide (ALCOIF), two come from the degradation of 2,3-didechloroethylifosfamide (2,3-DEC1IF), and one results from the decomposition of 2DEC1IF. The total cumulative drug excretion as measured over 24 h in nine patients was 51% of the injected IF dose; 18% of the dose was recovered as unchanged IF. The major urinary metabolites were the dechloroethylated compounds, with 3DEC1IF excretion (11% of the injected dose) always being superior to 2DEC1IF elimination (4% of the injected dose). Degradation compounds of 2DEC1IF and 2,3DEC1IF represented 0.4% of the injected dose. The metabolites of the dechloroethylation pathway always predominated over those of the activation pathway (CARBOXYIF, ALCOIF, and IPM, representing 3%, 0.8%, and 0.2% of the injected dose, respectively). In all, 14% of the injected dose was excreted as unknown phosphorated compounds. The interpatient variation in levels of IF metabolites was obvious and involved all of the metabolites. Renal excretion was not complete at 24 h, since 11% of the injected dose was recovered in the 24- to 48-h urine samples. PMID- 8431974 TI - Phase I clinical study of LL-D49194 alpha 1 with retrospective pharmacokinetic investigations in mice and humans. The EORTC ECTG. AB - LL-D49194 alpha 1 is a new cytotoxic antibiotic selected for clinical phase I study because of its impressive pre-clinical anti-tumour activity and its low toxicity profile in experimental animals. A total of 15 patients were treated in centres in Glasgow and Amsterdam at doses ranging from 0.25 to 4 mg/m2. One minor response was noted in a patient with colonic carcinoma. The study was suspended following the discovery of unexpected cardiotoxicity. As this toxicity was not consistent with the standard (EORTC) European Organisation for Research and Treatment of Cancer toxicology profile, we chose to investigate the pharmacokinetics of LL-D49194 alpha 1 in mice and humans in more detail to try to explain this phenomenon. A major difference in plasma protein binding was discovered between mice and patients, with a suggestion of non-linear kinetics being noted at higher doses in humans. It is likely that these differences in drug handling account for the unexpected and serious toxicity encountered in this trial. PMID- 8431975 TI - 1-dehydro-melengestrol acetate inhibits the growth and protein kinase C activity of androgen-independent Dunning rat prostatic tumors. AB - Androgen-independent Dunning R3327-AT3 rat prostate tumors are considered an appropriate model of advanced prostate cancer in humans. We recently reported that the progestational steroid melengestrol acetate (MGA) inhibited growth of these tumors on oral administration but also induced a marked involution of adrenals and androgen target organs (prostate, seminal vesicles, and testes). We report herein that the 1-dehydro derivative of melengestrol acetate (dMGA) fed to rats for 21 days also inhibited the growth of Dunning AT3 tumors by approximately 55% without causing a significant regression of adrenals or androgen-dependent tissues. Thus, tumor-growth inhibition was induced by dMGA in the absence of glucocorticoid activity. Cytosolic AT3 tumor fractions obtained by diethylaminoethyl (DEAE)-Sephacel batch chromatography were assayed for lipid- and Ca(2+)-dependent (PKC) and -independent protein kinase activities. Prostatic cytosols had equivalent activity levels of both types of kinases (approximately 2 nmol gamma-[32P]-adenosine 5'-triphosphate (ATP) incorporated mg protein-1 min-1. The PKC activity recovered from the cytosol of untreated AT3 tumors was approximately 4 times higher. Oral administration of dMGA reduced this activity by > 95%. The relationship between protein-kinase activity levels and dMGA induced growth inhibition of androgen-independent tumors in this animal model is discussed. PMID- 8431976 TI - Targeting chemosensitizing doses of toremifene based on protein binding. AB - Toremifene is currently being evaluated as a chemosensitizing agent in doxorubicin-resistant patients. Although concentrations of > 2 microM reverse resistance in vitro, target concentrations required to reverse multidrug resistance (MDR) in vivo may be highly influenced by variables such as protein binding in serum. We examined the effects of high serum concentrations on the cellular accumulation of toremifene in an MDR MDA-MB-A-1 human breast-cancer cell line. We then examined the cellular accumulation of doxorubicin at various toremifene concentrations in 5% - 100% serum. We also measured the concentrations of toremifene and its major metabolites in plasma specimens obtained from two patients receiving 360 mg/day for 5 days in a phase I study. Our results show that (1) high serum concentrations decrease toremifene accumulation, (2) toremifene concentrations of < or = 2.5 microM enhance doxorubicin accumulation, and (3) patients achieve plasma toremifene concentrations of 10-15 microM following doses of 360 mg/day x 5 days. Our findings suggest that in vivo toremifene concentrations well above those used to reverse resistance in vitro are required to overcome the effect of high serum-protein binding. PMID- 8431977 TI - Prohibitive toxicity of a dose-intense regime for metastatic neuroblastoma containing ifosfamide, doxorubicin and cisplatin. AB - Three patients with stage 4 neuroblastoma were treated with a schedule comprising alternating modules of myelosuppressive (ifosfamide, etoposide, doxorubicin) and less myelosuppressive (vincristine, cisplatin) drugs given every 10 days regardless of the neutrophil count. A partial response was seen in two patients, and a very good partial response, in one patient. Extensive blood-component support was required. Non-haemopoietic toxicity was severe and led to treatment delays in two patients. Ifosfamide-related encephalopathy was seen in one patient and nephrotoxicity, in two patients. Mucositis was severe in two patients, may have contributed to the high rate of sepsis observed, and precluded the use of doxorubicin in one patient. As ifosfamide and doxorubicin were felt to be responsible for much of the toxicity, a subsequent schedule did not include these agents. PMID- 8431978 TI - Phase II trial of the novel sulphonylurea sulofenur in advanced breast cancer. AB - A total of 18 women with advanced breast cancer were treated with sulofenur [LY186641; N-(5-indanylsulfonyl)-N'-(4-chlorophenyl)-urea], a diarylsulfonylurea that has broad-spectrum activity against a number of murine mammary tumour xenografts. The dosage chosen on the basis of pre-clinical and phase I studies was 700 mg/m2 given orally once daily for 14 days, with treatments being repeated every 3 weeks. There was no response. All patients experienced at least grade 1 anaemia, and two patients developed symptomatic methaemoglobinaemia. Two patients developed grade 4 rises in serum liver-function values along with histological changes consistent with drug-induced toxicity. The mean plasma concentrations of 176 micrograms/ml were lower than the levels required to exert anti-tumour effect in the mouse model. PMID- 8431979 TI - The effect of exchanger inhibitory peptide (XIP) on sodium-calcium exchange current in guinea pig ventricular cells. AB - We investigated the effect of exchanger inhibitory peptide (XIP) on Na-Ca exchange current (INa-Ca) in guinea pig ventricular cells. Cells were voltage clamped with microelectrodes containing 20 mM Na+ and 14.0 mM EGTA ([Ca]i = 100 nM). An outward putative exchange current was stimulated when extracellular Na+ was reduced from 144 mM to zero (Li+ replaced Na+). This outward current showed a significant dependence on extracellular Ca2+. When Na+ removal was delayed for up to 40 minutes (in the absence of extracellular K+ or the presence of 3.0 mM ouabain to block the Na+ pump), outward INa-Ca increased presumably because [Na]i increased. Time-dependent increases of outward current in the absence of K+ could be abolished by reapplication of K+, which presumably reactivates the Na+ pump and reduces intracellular Na+. This effect is blocked in the presence of 3.0 mM ouabain. The dependence of this current on extracellular Ca2+, its dependence on intracellular Na+, and activation by extracellular Na+ reduction, together with its resistance to ouabain all suggest that it is a Na-Ca exchange current. After dialyzing the cell with 10 microM XIP, outward INa-Ca was largely abolished. This indicates that XIP, which is a rather large molecule, can enter the heart cell via the microelectrode in sufficient quantities to inhibit exchange. Inward INa Ca was blocked secondary to the blockade of outward INa-Ca. L-type Ca2+ current (ICa) was not measurably affected by XIP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431980 TI - Heterogeneity of ATP receptors in aortic endothelial cells. Involvement of P2y and P2u receptors in inositol phosphate response. AB - Extracellular ATP plays an important role in the regulation of prostacyclin and nitric oxide release from vascular endothelial cells. These cellular responses to ATP are generally attributed to the stimulation of the P2y subtype of P2 purinergic receptors. However, it has recently been suggested that two types of ATP receptors might coexist on endothelial cells. To evaluate this hypothesis, we examined the effects of P2y receptor agonists 2-methylthioadenosine 5' triphosphate (2MeSATP) and 2'- and 3'-O-(4-benzoylbenzoyl)adenosine 5' triphosphate (BzATP) and of UTP on the accumulation of inositol phosphates in bovine aortic endothelial cells. BzATP, 2MeSATP, and UTP produced a smaller maximal effect than ATP. The effects of 2MeSATP and UTP were additive, whereas the effects of ATP and either UTP or 2MeSATP were not. Prior exposure to UTP reduced the subsequent response to UTP to 12% of the control response, whereas the response to 2MeSATP was decreased to 61%. Reciprocally, preincubation with 2MeSATP reduced the subsequent response to 2MeSATP to 23% of the control response, whereas the response to UTP was reduced to 73%. Pertussis toxin pretreatment decreased the response to both ATP and UTP (65% and 70% inhibition, respectively), whereas the response to 2MeSATP was not modified. Our data support the hypothesis that two classes of receptors recognizing ATP are expressed on bovine aortic endothelial cells. PMID- 8431981 TI - Inhibition of nitric oxide formation in the nucleus tractus solitarius increases renal sympathetic nerve activity in rabbits. AB - It has been shown that nitric oxide (NO) is synthesized in the central nervous system as well as in vascular endothelial cells. However, the physiological role of NO in cardiovascular regulation by the central nervous system remains unclear. This objective of this study was to examine the possibility that NO plays a role in neural transmission in the nucleus tractus solitarius (NTS) and thus contributes to control of sympathetic nerve activity in rabbits. We examined the effects of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of the formation of NO from L-arginine, microinjected into the NTS on arterial pressure (AP), heart rate (HR), and renal sympathetic nerve activity (RSNA). L-NMMA increased AP and RSNA in rabbits with intact as well as denervated sinoaortic baroreceptors and vagi. L NMMA increased HR only in rabbits with sinoaortic denervation and vagotomy. Pretreatment with L-arginine microinjected into the NTS, which did not alter baseline AP, HR, and RSNA, prevented the increases in AP and RSNA evoked with subsequent L-NMMA. Pretreatment with D-arginine did not alter the effects of subsequent L-NMMA injections into the NTS. The gain of arterial baroreflex control of RSNA assessed by the slope of the regression line relating changes in AP and those in RSNA caused by intravenous phenylephrine or nitroglycerin did not differ before and after microinjections of L-NMMA. L-NMMA microinjected into the area postrema did not alter AP, HR, or RSNA. These results suggest that in rabbits NO is involved in the mechanism in the NTS that mediates tonic inhibition of RSNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431982 TI - Acetylcholine reversal of isoproterenol-stimulated sodium currents in rabbit ventricular myocytes. AB - We have recently shown that beta-adrenergic agonists enhance the cardiac sodium current (INa) in rabbits through dual G-protein regulatory pathways. To determine if muscarinic cholinergic receptor stimulation can also modulate INa, we studied the effects of acetylcholine (ACh) and carbachol on INa in enzymatically dispersed rabbit ventricular myocytes. Whole-cell patch-clamp experiments done at room temperature using 20 mM [Na+]o showed that 100 nM isoproterenol increased INa and accelerated current decay as previously described. ACh (1 microM) or carbachol (1 microM) significantly reversed the stimulatory isoproterenol effects at test potentials throughout the INa activation range and at holding potentials negative to -80 mV. This effect was completely inhibited by atropine (1 microM) and was confirmed by studying single-channel INa from cell-attached patches. When INa was stimulated by forskolin (1 microM), carbachol (1 microM) significantly reversed the effect. The muscarinic-mediated inhibition of INa was inhibited by pertussis toxin (0.1 or 1.0 microgram/ml) incubation (12-15 hours), suggesting that the effect was inhibitory G-protein dependent. Further investigation of the ACh inhibitory mechanism revealed that ACh alone had no effect on INa and that when cells were dialyzed with cAMP (5 microM), ACh failed to inhibit INa. Furthermore, cGMP failed to inhibit the effect of isoproterenol on INa. These data suggest that ACh acts at or proximal to adenylate cyclase stimulation. Thus, rabbit cardiac Na+ channels are regulated by muscarinic agonists in a fashion similar to cardiac Ca2+ channels. PMID- 8431983 TI - Hepatorenal reflex plays an important role in natriuresis after high-NaCl food intake in conscious dogs. AB - Responses of renal nerve activity and urinary Na+ and Cl- excretion were examined in chronically instrumented conscious dogs through feedings of boiled rice with or without NaCl. The boiled rice (20 g/kg body wt) without NaCl did not influence plasma Na+ and Cl- concentrations, renal nerve activity, or urinary Na+ excretion but decreased urinary Cl- excretion. On the other hand, boiled rice containing NaCl (0.4 g/kg body wt) increased plasma Na+ (+3.8 +/- 0.7 meq/l) and Cl- (+3.0 +/- 1.5 meq/l) concentrations, then decreased renal nerve activity by 61 +/- 4%, and increased urinary Na+ and Cl- excretions. In dogs with hepatic denervation, a decrease in renal nerve activity, which was observed in intact dogs in response to the high-NaCl food intake, was completely abolished along with significant attenuation of postprandial natriuresis. That is, only 9 +/- 5% of the loaded Na+ and 7 +/- 3% of the loaded Cl- were excreted during 4 consecutive hours in hepatic-denervated dogs, whereas 36 +/- 5% of the loaded Na+ and 36 +/- 4% of the loaded Cl- were excreted in intact dogs. In dogs with renal denervation, postprandial natriuresis was also attenuated. These results indicate that the high-NaCl food intake elicits a decrease in renal nerve activity, the decrease is predominantly mediated by the hepatic nerves, and the decrease in renal nerve activity plays an important role in augmentation of urinary Na+ and Cl- excretion. Thus, the hepatorenal reflex may play an important role in controlling extracellular fluid homeostasis during food intake. PMID- 8431984 TI - Dissociation between cellular K+ loss, reduction in repolarization time, and tissue ATP levels during myocardial hypoxia and ischemia. AB - The mechanisms underlying the marked increase in [K+]o in response to ischemia are not fully understood. Accordingly, the present study was performed to assess the contribution of ATP-regulated K+ channels by using simultaneous measurements of cellular K+ efflux, [K+]o, transmembrane action potentials, and tissue ATP, ADP, phosphocreatine, and creatine content in a unique isolated, blood-perfused papillary muscle preparation during hypoxia compared with ischemia. During 15 minutes of hypoxic perfusion (PO2, 6.1 +/- 0.9 mm Hg) with normal [K+]o of 4.1 +/ 0.1 mM, action potential duration (APD) was not altered even though tissue ATP levels decreased markedly from 33.5 +/- 1.8 to 14.7 +/- 2.0 nmol.mg protein-1 (p < 0.01). Net cellular K+ efflux, based on measured differences of [K+] between the venous effluent and the perfusate, was 13.23 +/- 0.79 mumol.g wet wt-1 during hypoxia. In contrast, after 15 minutes of zero-flow ischemia, APD at 80% of repolarization (APD80) decreased by 47% from 171 +/- 5 to 92 +/- 5 msec (p < 0.01), but integrated net cellular K+ efflux over 15 minutes of ischemia was 8.4 fold less (1.57 +/- 0.13 mumol.g wet wt-1) than during hypoxia. Tissue ATP levels, however, decreased by only 35.2% to 21.7 +/- 2.1 nmol.mg protein-1, which was significantly less than that induced by 15 minutes of hypoxia. Perfusion with hypoxic blood containing high [K+]o of 10.3 +/- 0.3 mM resulted in APD shortening similar to that observed during ischemia. Cellular K+ loss, however, was inhibited markedly by high [K+]o perfusion (only 4.51 +/- 0.28 mumol.g wet wt-1). Pretreatment with glibenclamide (5 microM), a drug that has been reported to inhibit ATP-regulated K+ channels and accelerate glycolysis in normoxic tissue, partially inhibited cellular K+ efflux during hypoxic perfusion with normal [K+]o (7.35 +/- 0.71 versus 13.23 +/- 0.79 mumol.g wet wt-1, p < 0.01) but had no significant influence on repolarization time or tissue ATP levels. Although glibenclamide partially prevented action potential shortening induced by hypoxic perfusion in the presence of elevated [K+]o, the proportion of cellular K+ efflux reduced by glibenclamide was less (23%) than that observed with glibenclamide in hypoxic perfusion with normal [K+]o (44%).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8431985 TI - Coronary pressure-flow relation in left ventricular hypertrophy. Importance of changes in back pressure versus changes in minimum resistance. AB - Perfusion abnormalities in the pressure-overloaded hypertrophied left ventricle could result from an increase in minimum coronary resistance or an increase in effective back pressure due to increased extravascular compressive forces. Since the pressure-flow relation of the maximally vasodilated coronary bed allows dissociation of minimum resistance (inverse slope [1/alpha PF]) and back pressure (pressure at zero flow [Pf = 0]), the present study was undertaken to examine the coronary pressure-flow relation in left ventricular hypertrophy (LVH). Ascending aortic banding in eight dogs at 6-8 weeks of age (LVH group) increased the left ventricular to body weight ratio to 8.7 +/- 0.6 g/kg as compared with 4.8 +/- 0.2 g/kg in nine normal dogs (p < 0.05). Maximum coronary vasodilation was produced by infusion of adenosine (1 mg/kg per minute i.v.). The slope of the coronary pressure-flow relation (alpha PF) was 5.8 +/- 0.5 10(-2) (ml/min per gram)/mm Hg in the LVH group and 9.3 +/- 0.6 10(-2) (ml/min per gram)/mm Hg in the normal group (p < 0.05). alpha PF was significantly correlated with the left ventricular to body weight ratio but not with coronary pressure, suggesting that the degree of hypertrophy and not exposure to high coronary pressure was responsible for the observed decrease in alpha PF. Pf = 0 was 24.1 +/- 2.6 mm Hg in the LVH group and 11.7 +/- 1.2 mm Hg in the normal group (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431986 TI - Fetal ductus arteriosus ligation. Pulmonary vascular smooth muscle biochemical and mechanical changes. AB - To evaluate the smooth muscle mechanical and biochemical changes associated with persistent pulmonary hypertension syndrome of the newborn, we studied 31 fetal sheep in which the ductus arteriosus was ligated at 125 days of gestation. Sixty one noninstrumented and six sham-operated fetuses served as controls. All animals were delivered by cesarean section at 137-140 days of gestation, and the experimental group had the ductus arteriosus ligated for 12 +/- 3 days. The ligated group demonstrated a higher mean (+/- SEM) pulmonary artery pressure (72.3 +/- 3.8 versus 54.1 +/- 2 mm Hg, p < 0.01) and right ventricular mean free wall weight (12.5 +/- 0.7 versus 6.8 +/- 0.3 g, p < 0.01) as compared with the sham-operated group. Significant changes in the pulmonary vascular smooth muscle of the ligated group were observed. The myosin content of vessels from the second through fifth generation demonstrated a significant increase in actin and myosin content (p < 0.01), but given their disproportional changes, the noninstrumented group demonstrated a lower actin/myosin ratio than the experimental group (p < 0.01). Changes in the myosin heavy chain isoform stoichiometry, characterized by an increase in both the mean high/low myosin heavy chain isoform ratio (1.8 +/- 0.3 versus 1.0 +/- 0.1, p < 0.05) and the nonmuscle isoform as a percentage of the total myosin heavy chain (12.4 +/- 0.7% versus 2.7 +/- 0.9%, p < 0.01), were also observed in the ligated as compared with the noninstrumented animals. In addition, the muscle Mg-ATPase activity was significantly (p < 0.05) reduced in the experimental group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431987 TI - Effects of the positive inotropic agent Org 30029 on developed force and aequorin light transients in intact canine ventricular myocardium. AB - The action of a novel cardiotonic agent N-hydroxy-5,6-dimethoxy-benzo[b]thiophene 2-carboximide hydrochloride (Org 30029) on intracellular aequorin light transients and isometric contractions was investigated in isolated canine ventricular trabeculae. The positive inotropic effect of Org 30029 (30 microM-3 mM) was consistently associated with prolongation of the duration of contraction and an increase in the amplitude of the intracellular Ca2+ transients. The maximum inotropic response to Org 30029 was approximately 150% of the maximum response to isoproterenol, whereas the maximum increase in the amplitude of Ca2+ transients produced by Org 30029 was only 20% of the isoproterenol-induced maximum. The duration of isometric contractions was prolonged by Org 30029, with no change in the duration of the light transients. The concentration-response curve for the positive inotropic effect of Org 30029 was shifted by carbamylcholine chloride (carbachol, 3 microM) to the right and downward, but the maximum response to Org 30029 was greater than that to isoproterenol even in the presence of carbachol. Carbachol abolished the increase in light transients and cAMP accumulation induced by Org 30029 (1 mM), whereas it only partially attenuated the positive inotropic effect of Org 30029. In the presence of carbachol (3 microM), Org 30029 increased the force of contraction in a concentration-dependent manner without augmenting the aequorin light transients. These results are compatible with the hypothesis that Org 30029 increases cardiac contractility by increasing myofilament Ca2+ responsiveness. PMID- 8431988 TI - Coronary venular responses to flow and pressure. AB - In previous studies, we demonstrated that both endothelium-dependent flow-induced vasodilation and endothelium-independent myogenic responses occur in porcine coronary arterioles. However, it was not established whether these responses are present in the coronary venular microcirculation. The aim of this study was to test the hypotheses that 1) coronary venules, like arterioles, exhibit flow induced dilation and myogenic responsiveness, and 2) venular flow-induced dilation is endothelium-dependent and is mediated by the release of a nitrovasodilator. Experiments were performed in porcine subepicardial coronary venules, 80-120 microns in diameter, by using cannulated isolated vessel techniques to allow intraluminal pressure and flow to be independently controlled. Flow was initiated by simultaneously moving two perfusion reservoirs connected to the cannulating pipettes in equal amounts but in opposite directions. In the absence of flow, i.e., zero pressure gradient (delta P) between the two reservoirs, venules developed spontaneous tone to 75-80% of maximum diameter at 10 cm H2O intraluminal pressure. Venules gradually dilated in response to stepwise increases in flow (i.e., delta P). The threshold for the flow-induced dilation occurred at delta P = 1 cm H2O (flow = 3.5 nl/sec), and the maximal response (dilation to 93 +/- 2% of maximum diameter) occurred when delta P was elevated to > or = 6 cm H2O (flow = 21 nl/sec at delta P = 6 cm H2O). Flow induced dilation was abolished after the endothelium was damaged by perfusion of an air bolus through the lumen. Vasoconstriction was observed when denuded venules were subjected to relatively high luminal flows (> or = 21 nl/sec).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431989 TI - Spiral waves of excitation underlie reentrant activity in isolated cardiac muscle. AB - The mechanism of reentrant ventricular tachycardia was studied in computer simulations and in thin (approximately 20 x 20 x 0.5-mm) slices of dog and sheep ventricular epicardial muscle. A two-dimensional matrix consisting of 96 x 96 electrically coupled cells modeled by the FitzHugh-Nagumo equations was used to analyze the dynamics of self-sustaining reentrant activity in the form of elliptical spiral waves induced by premature stimulation. In homogeneous anisotropic media, spirals are stationary and may last indefinitely. However, the presence of small parameter gradients may lead to drifting and eventual termination of the spiral at the boundary of the medium. On the other hand, spirals may anchor and rotate around small discontinuities within the matrix. Similar results were obtained experimentally in 10 preparations whose electrical activity was monitored by means of a potentiometric dye and high-resolution optical mapping techniques; premature stimulation triggered reproducible episodes of sustained or nonsustained reentrant tachycardia in the form of spiral waves. As a rule, the spirals were elongated, with the major hemiaxis parallel to the longitudinal axis of the cells. The period of rotation (183 +/- 68 msec [mean +/- SD]) was longer than the refractory period (131 +/- 38 msec) and appeared to be determined by the size of the spiral's core, which was measured using a newly devised "frame-stack" plot. Drifting of spiral waves was also observed experimentally. Drift velocity was 9.8% of the velocity of wave propagation. In some cases, the core became stationary by anchoring to small arteries or other heterogeneities, and the spiral rotated rhythmically for prolonged periods of time. Yet, when drift occurred, spatiotemporal variations in the excitation period were manifested as a result of a Doppler effect, with the excitation period ahead of the core being 20 +/- 6% shorter than the excitation period behind the core. As a result of these coexisting frequencies, a pseudoelectrocardiogram of the activity in the presence of a drifting spiral wave exhibited "QRS complexes" with an undulating axis, which resembled those observed in patients with torsade de pointes. The overall results show that spiral wave activity is a property of cardiac muscle and suggest that such activity may be the common mechanism of a number of monomorphic and polymorphic tachycardias. PMID- 8431990 TI - Ionic bases for electrophysiological distinctions among epicardial, midmyocardial, and endocardial myocytes from the free wall of the canine left ventricle. AB - Recent studies from our laboratory involving syncytial preparations have delineated electrophysiological distinctions between epicardium, endocardium, and a unique population of cells in the deep subepicardial to midmyocardial layers (M region) of the canine ventricle. In the present study, we used standard microelectrode, single microelectrode switch voltage-clamp, and whole-cell patch clamp techniques to examine transmembrane action potentials, steady-state current voltage relations, and the 4-aminopyridine-sensitive transient outward current (Ito1) in myocytes enzymatically dissociated from discrete layers of the free wall of the canine left ventricle. Action potential characteristics of myocytes isolated from the epicardium, M region, and endocardium were very similar to those previously observed in syncytial preparations isolated from the respective regions of the ventricular wall. A prominent spike and dome was apparent in myocytes from epicardium and the M region but not in myocytes from endocardium. Action potential duration-rate relations were considerably more pronounced in cells isolated from the M region. Current-voltage relations recorded from cells of epicardial, M region, and endocardial origin all displayed an N-shaped configuration with a prominent negative slope-conductance region. The magnitude of the inward rectifier K+ current (IK1) was 392 +/- 86, 289 +/- 65, and 348 +/- 115 pA in epicardial, M region, and endocardial myocytes, respectively, when defined as steady-state current blocked by 10 mM Cs+. Similar levels were obtained when IK1 was defined as the steady-state difference current measured in the presence (6 mM) and absence of extracellular K+. Ito1 was significantly greater in epicardial and M region myocytes than in endocardial myocytes. At a test potential of +70 mV (holding potential, -80 mV), Ito1 amplitude was 4,203 +/ 2,370, 3,638 +/- 1,135, and 714 +/- 286 pA in epicardial, M region, and endocardial cells, respectively. No significant differences were observed in the voltage dependence of inactivation of Ito1 in the three cell types. The time course of reactivation of Ito1 was slower in cells from the M region compared with either epicardial or endocardial cells. Our data suggest that prominent heterogeneity exists in the electrophysiology of cells spanning the canine ventricular wall and that differences in the intensity of the transient outward current contribute importantly, but not exclusively, to this heterogeneity. These findings should advance our understanding of basic heart function and the ionic bases for the electrocardiographic J wave, T wave, U wave, and long QT intervals as well as improve our understanding of some of the complex factors contributing to the development of cardiac arrhythmias. PMID- 8431991 TI - Gene injection into canine myocardium as a useful model for studying gene expression in the heart of large mammals. AB - We have investigated the regulated expression of genes injected into the heart of large mammals in situ. Reporter constructs using the chloramphenicol acetyltransferase gene under the control of muscle-specific beta-myosin heavy chain (beta-MHC) or promiscuous (mouse sarcoma virus) promoters were injected into the canine myocardium. There was a linear dose-response relation between the level of gene expression and the quantity of plasmid DNA injected between 10 and 200 micrograms per injection site. The level of reporter gene expression did not correlate with the amount of injury imposed on the cardiac tissue. There was no regional variation in expression of injected reporter genes throughout the left ventricular wall. By use of both the mouse sarcoma virus and a muscle-specific beta-MHC promoter, reporter gene expression was one to two orders of magnitude greater in the heart than in skeletal muscle. Expression in the left ventricle was threefold higher than in the right ventricle. Chloramphenicol acetyltransferase activity was detected at 3, 7, 14, and 21 days after injection, with maximal expression at 7 days after injection. Statistical analysis of coinjection experiments revealed that coinjection of a second gene construct (Rous sarcoma virus-luciferase) is useful in the control of transfection efficiency in vivo. Furthermore, using reporter constructs containing serial deletions of the 5' flanking region of the beta-MHC gene, we performed a series of experiments that demonstrate the utility of this model in mapping promoter regions and identifying important regulatory gene sequences in vivo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431992 TI - Isoprenaline stimulates gene transcription of the inhibitory G protein alpha subunit Gi alpha-2 in rat heart. AB - In vitro transcription reactions were performed with isolated ventricular nuclei of adult rats to investigate whether increased mRNA levels of the inhibitory G protein alpha-subunit Gi alpha-2 after prolonged in vivo stimulation with the beta-adrenoceptor agonist isoprenaline are caused by increased transcription. Rats were treated by a 4-day subcutaneous infusion of isoprenaline (2.4 mg/kg per day) or 0.9% NaCl as control. To avoid the influence of developmental expression patterns, adult rats were chosen for all experiments. Signals for Gi alpha-2 and the stimulatory G protein alpha-subunit Gs alpha were specific and due to hybridization of nascent mRNA transcripts. In the isoprenaline group the transcriptional activity of Gi alpha-2 gene increased to 140% of the control value, whereas gene specific hybridization for Gs alpha remained unchanged. These results show that increased Gi alpha-2 mRNA levels after stimulation with isoprenaline are at least partially caused by enhanced transcription of Gi alpha 2 mRNA. PMID- 8431993 TI - Phosphatidic acid stimulates inositol 1,4,5-trisphosphate production in adult cardiac myocytes. AB - The cellular content of phosphatidic acid can increase in response to several agonists either by phosphorylation of diacylglycerol after phospholipase C catalyzed hydrolysis of phospholipids or directly through activation of phospholipase D. Although previous findings indicated that the generation of phosphatidic acid was exclusively a means of regulation of the cellular concentration of diacylglycerol, more recent studies have indicated that phosphatidic acid may also directly regulate several cellular functions. Accordingly, the present study was performed to assess whether phosphatidic acid could stimulate cardiac phospholipase C in intact adult rabbit ventricular myocytes. The mass of inositol 1,4,5-trisphosphate [Ins (1,4,5)P3] was determined by a specific and sensitive binding protein assay and by direct mass measurement using anion exchange chromatography for separation of selected inositol phosphates and gas chromatography and mass spectrometry for quantification of inositol monophosphate (IP1), inositol bisphosphate (IP2), inositol trisphosphate (IP3), and inositol tetrakisphosphate (IP4). Phosphatidic acid (10(-9)-10(-6) M) elicited a rapid concentration-dependent increase in Ins (1,4,5)P3 accumulation, with the peak fourfold to fivefold increase at 30 seconds of stimulation; the concentration required for 50% of maximal stimulation was 4.4 x 10(-8) M. The time course of individual inositol phosphates indicated a successive increase in the mass of IP3, IP4, IP2, and IP1 in response to stimulation with phosphatidic acid. The production of Ins (1,4,5)P3 in response to phosphatidic acid was not altered in the absence of extracellular calcium or in the presence of extracellular EGTA (10(-3) M). Thus, these findings indicate that phosphatidic acid is a potent activator of inositol phosphate production in adult ventricular myocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8431994 TI - Identification of a specific radioligand for the cardiac rapidly activating delayed rectifier K+ channel. AB - Class III antiarrhythmic drugs show promise as effective treatments for the suppression of potentially lethal cardiac arrhythmias. Dofetilide (UK-68,798), is a potent class III antiarrhythmic agent that is presently under clinical investigation. The objective of this study was to determine whether [3H]dofetilide could be used as a specific radioligand for the rapidly activating delayed rectifier K+ channel of the heart. We find that [3H]dofetilide binds to high-affinity sites on guinea pig cardiac myocytes. Competition studies using unlabeled dofetilide indicate that binding is characterized by an IC50 of 100 +/- 30 nM (mean +/- SD, n = 13). Scatchard analyses of binding indicate a Kd of 70 +/ 6 nM and a maximal binding capacity of 0.30 +/- 0.02 pmol/mg protein. [3H]Dofetilide is displaced from guinea pig myocytes by dofetilide, clofilium, quinidine, sotalol, and sematilide with a rank order of potency that correlates with functional blockade of the rapidly activating delayed rectifier K+ current (correlation coefficient, 0.951; slope, 0.99 +/- 0.19; p = 0.014). High-affinity [3H]dofetilide binding is not detected in rat myocytes, which are devoid of delayed rectifier K+ current. We conclude that [3H]dofetilide specifically binds to sites associated with the rapidly activating delayed rectifier K+ channel of guinea pig myocardium. PMID- 8431995 TI - Ovarian estrogen acts to feminize the female rat's corpus callosum. AB - The rat corpus callosum (CC) is sexually dimorphic, with the male CC being larger. Ovariectomy (Ovx) on day 12 has been shown to eliminate this sex difference, with callosal values of Ovx females approaching those of male controls. This suggested that postnatal ovarian estrogen affects the size of the female CC. In the present experiment, one group of female rats received Ovx on day 12, and a second group received Ovx followed by chronic implantation of a silastic tube containing beta-estradiol on day 25. Unmanipulated males and sham females served as controls. Examination of the CC at 110 days confirmed our prior findings that males have larger callosa than females and that the Ovx group had increased CC's compared to sham controls. Our new finding was that estrogen treatment was capable of reversing the effects of Ovx. Ovx+estrogen-treated females had decreased CC size as compared to Ovx alone. Indeed, they also had smaller CC values than control females. These findings indicate that ovarian estrogen plays a role in determining CC morphology and that estrogen in the female acts to inhibit overall callosal growth as measured by changes in gross callosal size. PMID- 8431996 TI - NCAM immunoreactivity during major developmental events in the rat maxillary nerve-whisker system. AB - The distribution of immunoreactivity for neural cell adhesion molecule (NCAM) has been characterized during the formation of the trigeminal ganglion and during the process of axon outgrowth and target differentiation in the maxillary nerve whisker system, in rat fetuses of known gestational age. Proliferating cells within the trigeminal placode are NCAM immunoreactive when first observed on embryonic day (E) 10. NCAM immunoreactivity is lost from placode-derived cells as they migrate to the trigeminal ganglion. It re-appears on ganglion cell somata and on centrally and peripherally projecting axons at the time of neurite outgrowth. NCAM-immunoreactive centrally projecting axons reach the developing brain stem two days before peripheral axons encounter the presumptive whisker pad. NCAM immunoreactivity on axons and somata is down regulated after P0, following target contact and whisker follicle differentiation. The presumptive dermis of the whisker pad at E13 appears as a sheet-like condensation of intensely NCAM immunostained cells. Discrete infraorbital row nerves can be identified on E13. These form in the subdermal region which contains only low levels of NCAM immunoreactivity. Condensations of NCAM immunostained mesenchyme replace the dermal sheet on E14 and each condensation is associated with a plexus of infraorbital nerve fibers. The epithelium overlying each condensation grows downward on E15. Focal epithelial regions become NCAM immunoreactive by E18. NCAM immunostaining within epithelial components of the whisker follicle is temporally correlated with contact by NCAM-immunoreactive infraorbital nerve fibers. The site restricted expression of NCAM immunoreactivity during trigeminal embryogenesis is consistent with the idea that NCAM plays an integral role in critical aspects of pattern formation in the maxillary nerve-whisker system, particularly in the organization of placode and non-placode derived trigeminal neuroblasts, axon outgrowth and in the differentiation of the vibrissae follicles. PMID- 8431997 TI - Parallel development of acetylcholinesterase in vivo and in primary neuron surface culture. AB - The development of acetylcholinesterase (AChE) activity in primary surface cultures of mouse cortical neurons and in mouse brain was examined. The specific activity of AChE in culture increased over 600% during a 3 week period and closely paralleled the development of AChE observed in vivo. The results obtained in this study show that a developmental increase in AChE can be obtained in primary surface neuron cultures, and that the high degree of cellular organization previously deemed necessary for this development in vitro is not as important as previously thought. PMID- 8431998 TI - Age of donor influences ability of suprachiasmatic nucleus grafts to restore circadian rhythmicity. AB - Previous studies have shown a high (80-90%) rate of restoration of circadian rhythmicity in suprachiasmatic nucleus (SCN)-lesioned adult hamsters given anterior hypothalamic tissue containing the SCN taken from fetal day 13-15 donors. In the present experiments we explored the influence of age of donor on morphological and functional characteristics of the SCN graft, using tissue taken from animals at postnatal day 1, 3, 5, 7 and 10. Grafts taken from older donors tend to reach a smaller overall final size than those from younger donors, and are more likely to contain isolated, medium sized NP-positive neurons. The rate of restoration of locomotor rhythmicity following transplantation of postnatal day (PN) 1 grafts is as high as that of embryonic grafts. By PN 3, the rate of restoration falls to about 50%, and grafts of PN 7 and 10 do not restore function. As in the case of fetal grafts, there is a strong correlation between the ability of a graft to restore locomotor rhythmicity, and the presence of a cluster of vasoactive intestinal peptide (VIP) and neurophysin (NP) cells characteristic of the intact SCN within the graft. Since the period of neurogenesis for the hamster SCN occurs between day 10.5 and day 13 postfertilization, the results indicate that the SCN can be transplanted successfully well beyond the period of neurogenesis. PMID- 8431999 TI - Correlations between developmental ornithine decarboxylase gene expression and enzyme activity in the rat brain. AB - The rise and decline in cerebral ODC activity during specific stages of development has been attributed to cytoplasmic intermediates which regulate ornithine decarboxylase activity. Here we examine whether transcriptional regulation contributes to the production of the developmental profiles of ODC activity. Postnatal cerebellar and neocortical tissue were obtained from Long Evans hooded rats at postnatal days (PND) 5, 10, 15, 20, 25, 30, 90 and probed for ODC and actin gene expression, by Northern analysis. Our results indicate that ODC gene expression in the cerebellum was elevated at PND 5 and 10 followed by a gradual drop to the adult low levels by PND 20. By contrast, high levels of ODC gene expression in the neocortex were seen at PND 5 with an abrupt decrease at day 10 to low adult levels. The expression of the ODC gene in the neocortex follows closely the pattern for the ODC enzyme activity; however, it tends to remain elevated longer in the cerebellum. The levels of actin gene expression exhibited a distinct developmental profile in the postnatally developing cerebellum. However, actin mRNA levels remained unchanged in the neocortex, consistent with the prenatal development of this region. Our findings suggest that ODC gene expression may play an important role in the production of the ontogenetic patterns of ODC activity. PMID- 8432000 TI - Increase in size of the caudate nucleus of the cat after a prenatal neocortical lesion. AB - In order to study the influence of prenatal developmental factors upon reaction of the brain to injury, fetal kittens (E43-48) were lesioned in the frontal or parietal cortex unilaterally and maintained into young adulthood. The animals were sacrificed by perfusion with an aldehyde fixative or by an overdose of pentobarbital. Frozen sections were cut and stained with thionin. These sections were used for calculation of caudate nuclei volumes and for measurements of neuronal and glial cell packing density and neuronal cell body size. Island and matrix compartments were sampled separately. We found that the volume of the ipsilateral caudate nucleus had significantly increased as compared to (a) the volume of the corresponding nucleus in intact cats (mean, 15%) and (b) the nucleus contralateral to the lesion (mean, 7.6%). The latter nucleus also tended to a volume increase (mean, 8.1%). The cytoarchitecture of the caudate nuclei was essentially unchanged with two exceptions. The neuronal cell packing density in the matrix compartment of the contralateral side was decreased (mean, 14.9%) while the size of neuronal cell bodies in the island compartment of the nucleus ipsilateral to the lesion was smaller (mean, 5%) relative to controls. These findings suggest that the number of neurons in the caudate of lesioned animals was larger than in intact controls, particularly on the lesioned side of the brain. This might be due to a reduction of naturally occurring cell death during development. PMID- 8432001 TI - Induction of agenesis of the corpus callosum by the destruction of anlage of the olfactory bulb using fetal laser surgery exo utero in mice. AB - It has long been discussed why some congenital anomalies were often involved with abnormalities in other organs, for example, brain anomalies accompanied by limb anomalies or cleft palate. The mechanism of combined abnormalities has been mysterious, and usually explained as pleiotropism. A combination between agenesis of the olfactory bulb and agenesis of the corpus callosum has been reported. In the present experiments, it has been suggested that non-attachment of the olfactory nerve to the rostro-ventral tip of the telencephalon blocked the induction of the olfactory bulbs from the telencephalon in genetic arhinencephalic mouse embryos. It was shown that the destruction of the olfactory bulb anlage using fetal laser surgery exo utero becomes a trigger of agenesis of the corpus callosum and irregular connection of the anterior commissure in later morphogenesis of the mouse brain. We believe that a fetal surgical experiment like this will make clear the morphogenetic mechanism of the combined abnormalities that have been previously explained as pleiotropism. PMID- 8432002 TI - Developmental changes in rat adrenal enkephalin precursor: peptide ratio. AB - Developmental changes in rat adrenal [Met5]enkephalin (ME) immunoreactivity and [Met5]enkephalinargininephenylalanine (MERF) immunoreactivity (which presumably reflects proenkephalin) were examined. The concentration of MERF appeared highest at the end of the first week postnatally and decreased fourfold to near adult values by day 21, while ME levels decreased only about twofold. This indicates a fall in the adrenal proenkephalin:ME ratio during the transition from the suckling to the weanling period in the rat. The elevated MERF levels during the suckling period may result from deficient processing of proenkephalin to free ME. An increase in the activity of the processing enzyme carboxypeptidase E was observed at day 15, which may contribute to the developmental fall in the adrenal proenkephalin to free ME ratio. Mimicking sympathetic activity by nicotine treatment (3 mg/kg i.p. twice daily from birth) produced a precocious decrease in the MERF:ME ratio at day 8, and also increased the activity of the processing enzyme. Denervation at day 10 markedly decreased adrenal ME and produced a three fold increase in MERF:ME ratio when measured at day 30. Adrenal carboxypeptidase E activity was also decreased after denervation. In summary, these results suggest that increasing preganglionic sympathetic nerve activity during the third week postnatally stimulates proenkephalin processing and leads to the developmental decrease in MERF:ME ratio in the rat adrenal. PMID- 8432003 TI - Structural modifications associated with synaptic development in area CA1 of rat hippocampal organotypic cultures. AB - Using morphological techniques, we characterized the developmental reorganization that takes place during the first weeks after explanation in area CA1 of organotypic hippocampal cultures maintained at the interface between medium and a CO2-enriched atmosphere. Pyramidal neurones redistributed from a vertical into an horizontal cell layer in the middle of a three-dimensional culture, with apical dendrites running above the pyramidal layer. Glial cells redistributed into a thin layer at the bottom of the culture, forming an interface between tissue and culture medium. Astrocytes were identified as the most numerous non neuronal cells. No sign of glial proliferation could be observed, except for a transient increase during the first days after explanation. The density of synaptic contacts in the stratum radiatum decreased immediately after explanation and then increased by about 20-fold to reach values in the proximal part of the apical layer after 4 weeks in culture which were only slightly smaller than those measured in 1-month-old rats. The synaptic density in the most distal part of the dendritic layer which receives connections extrinsic to the hippocampus remained significantly lower than in vivo. The ratio of spine to shaft contacts was comparable to that found in vivo. These results indicate that interface type of organotypic cultures can be used as an interesting model for studies of synaptic development in vitro. PMID- 8432004 TI - Time course of synaptic development in hippocampal organotypic cultures. AB - Using electrophysiological recordings of field potentials, we investigated the time course of synapse formation and maturation in organotypic cultures prepared from neonate animals of different ages. Following explanation, the size of the maximal synaptic responses elicited in area CA1 by stimulation of a small group of CA3 neurons increased progressively during the first three weeks in culture in a way that corresponded to the changes observed in synaptic contact density. Growth of synaptic responses was found to occur much more rapidly in cultures prepared from 8-day-old as compared with 2-day-old rats. Development of synaptic connections between CA3 and CA1 neurones was also faster than between granule cells and CA3 neurones. Acquisition of mature synaptic properties occurred in vitro as indicated by changes in degree of paired-pulse facilitation and the onset of long-term potentiation (LTP) after a few days in culture. The onset of LTP was much faster in cultures prepared from 8-day-old as compared with 2-day old neonates and corresponded approximately to the 12-14th postnatal day. It is concluded that development proceeds in the cultures with a time course that resembles the in situ situation. PMID- 8432005 TI - FDA ignores CLIA and moves to regulate clinical laboratories. PMID- 8432006 TI - Quantitative analyses of the interaction between calcium ions and human serum albumin. AB - We examined the suitability of nine organic buffers for studying calcium binding to albumin by equilibrium dialysis. Results obtained with defatted human serum albumin showed that 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) and 2-([tris(hydroxymethyl)methyl] amino)ethanesulfonic acid were superior. Scatchard analysis of the experimental data from an extensive study performed in HEPES at pH 7.4 and 20 degrees C revealed (putting n(i) = 1, i = 1-4) k1 = 367 L/mol, k2 = 314 L/mol, k3 = 291 L/mol, and k4 = 179 L/mol. The very weak binding was characterized as n5 = 10 and k5 = 40 L/mol. The results were also analyzed in terms of stoichiometric association constants. The constants K1 and K2 were calculated to be 1513 and 647 L/mol, respectively, whereas the other constants were considered undeterminable. pH studies showed that in the interval 6.8-7.4, binding was not influenced by changes in acidity. Increasing pH to above the physiological value resulted in increased binding. At pH 8.0, k1 was increased almost fourfold, whereas k2 and k3 were approximately doubled. These findings indicate that the neutral to basic transition is important for the calcium binding properties of albumin. The transition is a reversible, gradual conformational change of the protein at pH 6-9. PMID- 8432007 TI - Coronary artery disease risk predicted by plasma concentrations of high-density lipoprotein cholesterol, apolipoprotein AI, apolipoprotein B, and lipoprotein(a) in a general Chinese population. AB - We measured lipid and lipoprotein concentrations in blood samples from control subjects and patients with coronary artery disease (CAD) in Taiwan. We found significant differences (P < 0.01) in the concentrations of high-density lipoprotein cholesterol (HDLC), apolipoprotein AI (ApoAI), apolipoprotein B (ApoB), and lipoprotein(a) [Lp(a)]. Concentrations of HDLC < 350 mg/L, ApoAI < 900 mg/L, ApoB > 800 mg/L, and Lp(a) > 200 mg/L occurred, respectively, 2.8, 5.2, 1.7, and 2.3 times more frequently in the patients than in the control group. If one considers HDLC at < 350 mg/L, ApoAI at < 900 mg/L, ApoB at > 800 mg/L, and Lp(a) at > 200 mg/L as separate risk factors for CAD, the ratio of individual patients to control subjects having 4, 3, 2, 1, or 0 risk factors was [symbol: see text] 9.4, 2.1, 0.2, 0.2, respectively. Individuals displaying three or more risk factors were found 15 times more frequently in the CAD group than in the control group. These risk factors may be used clinically for the prediction and prevention of CAD in the general population. PMID- 8432008 TI - Distribution of cyclosporin G (NVa2 cyclosporin) in blood and plasma. AB - We report here on the distribution of cyclosporin G (CsG), an analog of cyclosporin A, in whole blood. CsG has a temperature-dependent distribution between erythrocytes (RBCs) and plasma. After 30 min at 37 degrees C, the plasma/whole blood and plasma/RBC ratios were relatively constant (0.7-0.8) up to CsG at 1000 micrograms/L. At 5000 micrograms/L, this ratio increased to 1.0-1.1 for plasma/whole blood and 1.7 for plasma/RBC. The primary CsG metabolites GM1 and GM9 were sequestered within RBCs to a greater extent than was the parent drug. In whole blood, approximately 2% of CsG was bound to granulocytes, 6% to lymphocytes, and 50-55% to RBC, and 35-40% was found in the plasma fraction. The free fraction of the drug as determined by ultracentrifugation was 5-6% and 13 17% of total drug at 37 and 4 degrees C, respectively. In plasma the drug was primarily associated with high-density lipoprotein (50-60%) and to a lesser degree with low-density (20-30%) and very-low-density (10%) lipoproteins. PMID- 8432009 TI - Hepatic and lipoprotein lipases selectively assayed in postheparin plasma. AB - Sensitive, reliable procedures are reported for the selective assay of lipoprotein lipase (LPL) and hepatic lipase (HL) in postheparin plasma samples. LPL is inhibited in the HL assay by inclusion of 0.76 mol/L sodium chloride in the substrate. In the LPL assay, specificity is attained by pretreating the sample with sodium dodecyl sulfate, which selectively denatures HL. This LPL method was validated by direct comparison with a procedure in which HL is inactivated by an antiserum to human HL. We used the described assays to quantify LPL and HL activity in 32 normal adults, demonstrating a clear sex difference for both enzymes. On average, the men displayed higher HL and lower LPL activities than did the women. PMID- 8432010 TI - Modifying an enzyme immunoassay of immunoreactive trypsinogen to use time resolved fluorescence. AB - A coated microtiter-well, enzyme-linked immunometric assay for quantifying immunoreactive trypsinogen in dried blood spots was modified to use time-resolved fluorescence of europium in place of end-point enzymatic color development as the quantification step. The streptavidin-horseradish peroxidase and color development solutions supplied as packaged reagents were replaced by europium labeled avidin, and the signal was developed with commercially available enhancement solution and read by time-resolved fluorescence. The change of label from enzyme to europium increased the dynamic range of the assay by about 5-fold, reduced the detection limit 10-fold, and halved the intra- and interassay imprecision. The improved analytical precision and stability of the modified assay resulted in a more precise description of the population distribution of immunoreactive trypsinogen values in newborns, showing less variance in the upper centiles. This effect is of paramount importance when using this assay for neonatal screening for cystic fibrosis. PMID- 8432011 TI - Does tumor-derived human chorionic gonadotropin act as a thyroid stimulator in vivo? AB - To evaluate in vivo the proposed intrinsic thyroid-stimulating hormone (TSH) activity (TSA) of human chorionic gonadotropin (hCG), we monitored over 0.5-1 years the thyroid status of eight patients with hCG-producing non-seminomatous testicular cancer. The patients' sera were analyzed for concentrations of hCG, free thyroxine (fT4), hTSH, and thyroxine-binding globulin (TBG). All patients had excessively high concentrations of hCG (1 x 10(5)-5 x 10(8) ng/L, mean: 1 x 10(7) ng/L) before polychemotherapy, which decreased under successful therapy to physiological values (< 240 ng/L). Although the serum concentrations of hCG varied by more than six orders of magnitude, we saw no changes and no correlation (P > 0.05) between the concentrations of hCG and the concentrations of fT4 and hTSH. Not even when hCG concentrations were greatest (> 5 x 10(7) ng/L) were any signs of hyperthyroidism observed: fT4 (3.5-13 ng/L) and hTSH (9-700 ng/L) were in the physiological range in all patients and remained so during chemotherapy. The results of this longitudinal study were confirmed in analyzing the data for all eight patients (total: 82 samples) cross-sectionally. Again, we found no correlation (P > 0.05) between the concentrations of hCG and fT4 or hCG and hTSH. We conclude that even excessive amounts of testicular tumor-derived hCG do not display any TSH-like activity in vivo. PMID- 8432012 TI - Nonradioactive, colorimetric microplate hybridization assay for detecting amplified human immunodeficiency virus DNA. AB - A nonradioactive, colorimetric microplate hybridization procedure was used to assay human immunodeficiency virus (HIV) DNA, amplified by the polymerase chain reaction (PCR). Under the PCR conditions used, four proviral copies per 150,000 cells were detected by amplifying a series of DNA mixtures that contained various copy numbers of HIV. Assays of PCR-amplified DNA from peripheral blood mononuclear cells of seronegative individuals yielded negative results (104 of 104), whereas samples from seropositive individuals yielded > 99% positive results (141 of 142). Similar results were obtained in a chemiluminescent assay with an acridinium ester-labeled probe and in a solution hybridization assay in which a 32P-labeled probe was used. PMID- 8432013 TI - Isocratic HPLC assay with electrochemical detection of free gamma-aminobutyric acid in cerebrospinal fluid. AB - A method for measuring gamma-aminobutyric acid (GABA) in human cerebrospinal fluid (CSF) by isocratic HPLC with electrochemical detection is described. The method is based on precolumn derivatization of GABA with o-phthaldialdehyde (OPA) and tert-butylthiol (t-BT), separation of the GABA-OPA complex on a reversed phase column, and quantitation by means of a Coulochem electrochemical detector. The method is highly sensitive and specific for GABA. In three samples of human CSF containing low, medium, and high amounts of GABA, the coefficients of variation between and within runs were 4.5% and 3.6%, respectively. The concentration of GABA in 10 neurologically intact subjects was 92.5 +/- 9.4 nmol/L of CSF. PMID- 8432014 TI - Multiwavelength photometry of thermochromic indicator solutions for temperature determination in multicuvettes. AB - If buffer/indicator systems are used as optical thermometers in multicuvettes, the temperature resolution is limited by errors of optical measurements produced mainly by variations of pathlength and blank transmittance of the wells. Theoretical and practical approaches show that, in multicuvettes, a between-well temperature resolution of < 0.05 degrees C can be achieved by multiwavelength photometry with use of the Tris/cresol red indicator system. Using up to three absorbances (A0, A1, A2) measured in the same well at different wavelengths for calculation of differences, quotients, and quotients of differences, we found the optimum temperature signal to be In(A1/A2), with equal-ranking absorbances changing with temperature in opposite directions. We have used the method successfully to measure the temperature profiles and temporal dynamics of temperatures at all positions in two types of multicuvettes under controlled conditions, or not controlled thermostatically. PMID- 8432015 TI - Homocysteine and other thiols in plasma and urine: automated determination and sample stability. AB - We have developed a modified version of our fully automated column-switching HPLC method for determining total plasma homocysteine based on single-column (reversed phase) separation. Homocysteine, cysteine, and cysteinylglycine in plasma (total concentrations), acid-precipitated plasma (non-protein-bound concentrations), and urine can be determined. The derivatization and chromatography were performed automatically by a sample processor. The successful separation of all thiol species (within 15 min) was accomplished by accurate adjustment of the pH of the mobile phase to 3.65 (plasma) or 3.50 (acid-precipitated plasma, urine). Maximal fluorescence yield of cysteine, cysteinylglycine, and, to a lesser degree, homocysteine was dependent on optimal concentrations of EDTA and dithioerythritol during reduction (with NaBH4) and derivatization (with monobromobimane). The method is sensitive (detection limit approximately 0.05 pmol) and has a high degree of precision (CV < 5%). The sample output is approximately 70 samples in 24 h. Serum and heparin plasma can also be analyzed. Hemolysis up to approximately 2.0 g/L of hemoglobin did not interfere with the analytical recovery of homocysteine or cysteine. Collection of blood, separation of plasma from whole blood, and acid precipitation must be standardized to obtain reproducible thiol results. Our modifications and the standardization of blood sampling procedures have substantially improved the method and broadened its applications. PMID- 8432016 TI - Multicenter evaluation of Reflotron direct dry-chemistry assay of high-density lipoprotein cholesterol in venous and fingerstick specimens. AB - The Reflotron HDL Cholesterol test (Boehringer Mannheim GmbH) directly separates and analyzes high-density lipoprotein (HDL) cholesterol in plasma collected with EDTA in an integrated dry-reagent system suitable for alternative site testing of lipoproteins. We describe a multicenter evaluation of this test by two US and six European laboratories experienced in lipid analysis. Each laboratory compared the Reflotron with the same conventional wet-chemistry method, Boehringer phosphotungstate-Mg2+ precipitation with enzymatic cholesterol assay. Imprecision was within accepted guidelines, with CVs of < or = 8% for fresh and frozen plasmas (median CV 1.7-3.9%) and for lyophilized sera (median CV 3.8-4.7%), similar to those of the conventional method. Results of linear-regression analysis were as follows: Reflotron HDL Cholesterol = 1.03 conventional - 3.9 mg/L, r = 0.987. The Reflotron results were somewhat low in the two US laboratories, demonstrating the need for general standardization of methods for measuring HDL cholesterol. Results from capillary fingerstick plasma agreed well with those from venous-derived plasma; capillary = 1.04 venous + 4.5 mg/L, r = 0.967. The system is relatively insensitive to interference from hemoglobin (< or = 0.75 g/L), ascorbic acid (< or = 0.3 g/L), bilirubin (< or = 50 mg/L), cholesterol (< or = 3.5 g/L), and triglycerides (< or = 4 g/L). The relative ease of operation and the rapid availability of results (within 90 s for plasma collected in EDTA) make the method appropriate for use by well-trained, but not necessarily technical, operators in the physician's office or other alternative sites. PMID- 8432017 TI - Selective removal of beta 2-microglobulin from plasma specimens of long-term hemodialysis patients by high-performance immunoaffinity chromatography. AB - We examined the suitability of high-performance immunoaffinity chromatography (HPIAC) for removing beta 2-microglobulin (beta 2-MG) from plasma of patients (n = 26) undergoing long-term hemodialysis. We used immobilized antibody to beta 2 MG to prepare an immunoaffinity column with a 0.5-mL bed volume. Plasma samples of 0.5 mL were chromatographed at a flow rate of 0.5 mL/min and pressures < 7 kg/cm2. Although only a small amount of beta 2-MG can be removed with a conventional dialyzer, 92.1% +/- 0.4% of the globulin could be removed by HPIAC. The column could be reused after acid elution. After 50 cycles the efficiency of beta 2-MG trapping was 73% of the original efficiency. PMID- 8432018 TI - Laboratory diagnosis of medium-chain acyl-coenzyme A dehydrogenase deficiency by the amplification refractory mutation system. AB - We used the amplification refractory mutation system (ARMS)--a polymerase-chain reaction-based method--to detect the 985 A-to-G mutation of the gene coding for the enzyme medium-chain acyl-CoA dehydrogenase (MCAD). The 985 A-to-G allele is thought to account for approximately 89% of the mutant alleles in this disorder and at least one copy was reported to be present in 98% of affected individuals. ARMS provided a simple and robust method that reliably identified the 985 A-to-G mutant allele in patients either homozygous or heterozygous for this allele. Combined with organic acid analysis, ARMS can provide definitive diagnosis for the great majority of the patients with MCAD deficiency. The method, therefore, should be useful in clinical laboratories involved with the diagnosis of inborn errors of metabolism. PMID- 8432019 TI - Evaluation of a novel point-of-care system, the i-STAT portable clinical analyzer. AB - We evaluated a novel system designed for rapid, point-of-care measurement of sodium, potassium, chloride, urea nitrogen, glucose, and hematocrit. The i-STAT Portable Clinical Analyzer (PCA) system is composed of a hand-held analyzer and disposable cartridges. Sample analysis takes place in the cartridge, which contains a series of thin-film electrodes microfabricated on silicon chips. The PCA was evaluated for precision, accuracy, and utility in emergency department and stat laboratory settings. Precision did not differ significantly between these two locations, the CVs being as follows: sodium, 0.46-0.89%; potassium, 1.06-1.45%; chloride, 0.69-2.76%; urea nitrogen, 2.54-6.12%; and glucose, 4.39 5.19%. The assessment of accuracy was based on comparison of patients' sample values analyzed by the PCA and the Kodak Ektachem 700 (or the Coulter ST for hematocrit). Regression statistics were acceptable for all analytes except chloride, for which the regression data were influenced by the limited range of results. A difference plot of the chloride comparison showed that the bias rarely exceeded 5 mmol/L. Mean hematocrit values significantly differed between the PCA and the Coulter ST, apparently because of different calibration procedures. PMID- 8432020 TI - Total error assessment of five methods for cholesterol screening. AB - We report the accuracy, imprecision, total analytical errors, and patient misclassification errors for cholesterol measured from capillary whole blood, venous whole blood, and venous plasma samples by five devices used in public cholesterol screening environments: Reflotron, Vision, Ektachem DT-60, QuickRead, and Liposcan. None of the methods met the National Cholesterol Education Program (NCEP) performance recommendations of 3% CV with 3% bias. The Vision and Reflotron methods used with venous samples gave individual results with total errors consistent with a combined CV and bias in the 4-5% range; capillary blood samples had total errors > 5% (combined CV and bias criteria). The DT-60 performance was near the 5% total error criterion for capillary samples and was > 5% for venous samples. Misclassification of individuals into desirable or referral groups for venous samples was as great as 5.1% for the DT-60, 5.7% for the Vision, and 7.1% for the Reflotron. Misclassifications for capillary blood samples were as great as 6.7%, 18.3%, and 14.1% for DT-60, Vision, and Reflotron, respectively. The QuickRead and Liposcan results were substantially poorer than those obtained by the other methods. PMID- 8432021 TI - Time-resolved immunofluorometric assay of complement C3: application to cerebrospinal fluid. AB - Complement components have a role in various neurological disorders. Complement C3 can be measured by immunochemical methods, but only radioimmunoassays and electroimmunodiffusion assays (EIDs) are sufficiently sensitive to be applied to biological fluids in which the C3 concentration is low, especially cerebrospinal fluid (CSF). We report a sandwich-type time-resolved immunofluorometric assay (TR IFMA) for C3 in CSF. The linearity (0.7-3650 micrograms/L) and intra- (CV < 4.8%) and inter-assay (CV < 10.9%) precision were satisfactory and the results agreed with those of EID. The assay is extremely sensitive (< 1 microgram/L) and its analytical range is large and well suited to clinical applications. This simple TR-IFMA is thus a nonisotopic alternative to radioimmunoassay for the quantification of complement C3 in CSF. PMID- 8432022 TI - Tissue-specific promoters regulate aromatase cytochrome P450 expression. AB - In humans, estrogen biosynthesis occurs in several tissue sites, including ovary, placenta, adipose, and brain. Recent work from our laboratory indicates that tissue-specific expression of aromatase cytochrome P450 (P450arom), the enzyme responsible for estrogen biosynthesis, is determined, in part, by the use of tissue-specific promoters. Thus, the expression of P450arom in human ovary appears to utilize a promoter proximal to the translation start site. This promoter is not utilized in placenta; instead, the promoter used to drive aromatase expression in placenta is > or = 40 kb upstream from the translational start site. In addition, a minor promoter used in the expression of a small proportion of placental transcripts is 9 kb upstream from the start of translation. Transcripts from these promoters are also expressed in other fetal tissues, including placenta-related cells such as JEG-3 choriocarcinoma cells and hydatidiform moles and other fetal tissues such as fetal liver. In adipose tissue, on the other hand, expression of P450arom may be achieved by yet another, adipose-specific promoter. The various 5'-untranslated exons unique for expression driven by each of these promoters are spliced into a common intron/exon boundary upstream from the translational start site. This means that the protein expressed in each of the various tissue-specific sites of estrogen biosynthesis is identical. PMID- 8432023 TI - Assessment of the role of G proteins and inositol phosphate production in the action of gonadotropin-releasing hormone. AB - The first step in gonadotropin-releasing hormone (GnRH) action involves the binding of GnRH to a plasma membrane receptor. Calcium has been implicated as a second messenger molecule. More recently, it has been suggested that the products of phosphoinositide metabolism may act as a second messenger for GnRH-stimulated release of luteinizing hormone (LH). To be considered a second messenger, however, a candidate molecule must meet three requirements: in the second messenger's presence, (a) GnRH should stimulate increased production of inositol phosphate; (b) inositol phosphate production, stimulated by any means, should provoke LH release; and (c) inhibition of inositol phosphate production should block GnRH-stimulated release of LH. PMID- 8432024 TI - Transcriptional regulation of human genes for steroidogenic enzymes. AB - Steroid hormones are synthesized from cholesterol in the adrenals, gonads, and placenta by a complex series of reactions. The human genes encoding each of these biosynthetic enzymes have been cloned, permitting study of their regulation. Tropic hormones, such as corticotropin and the gonadotropins, exert their chronic effects on steroidogenesis by increasing the amounts of steroidogenic enzymes; this in turn occurs primarily through increased gene transcription. Our studies have emphasized the cholesterol side-chain cleavage enzyme P450scc, which catalyzes the first and rate-limiting step in steroidogenesis, and P450c17, which determines what class of steroids is synthesized. By fusing the promoters of the genes for these enzymes to readily assayed reporter genes and transiently transfecting cultured cells with these constructions, we have identified the regions of each promoter that confer basal expression, induction by cAMP, and repression by activators of protein kinase C. Different segments of the P450scc promoter are used for each of these purposes in different cell types, indicating that the regulation of this gene is very complex. Transcription is not the only level at which steroidogenesis is regulated. The abundance of mRNA for adrenodoxin reductase, a flavoprotein needed for P450scc activity, is post transcriptionally regulated by cAMP. PMID- 8432025 TI - Transcriptional activation of the estrogen receptor. AB - Almost all breast cancer tumors progress to a hormone-resistant state. Evidence is presented that the existence of mutant estrogen receptors may explain some hormone-resistant phenotypes. Breast tumor cells bearing a mutant receptor that is constitutively active and does not bind hormone would have unregulated cell growth and thus appear to be hormone-independent. Alternatively, breast cancer cells may contain estrogen receptors that are transcriptionally inactive but when co-expressed with wild-type receptors render normal estrogen receptors inactive. These cells would be considered estrogen receptor-positive but would be hormone resistant. The hormone-resistant phenotype could be further complicated by the finding that other nonreceptor proteins may also modulate the transcriptional activity of estrogen receptors. These findings, if substantiated in vivo, could add to the complexity of the hormone-resistant phenotype. Different strategies of treatment will need to be developed to effectively treat the various subtypes of hormone-resistant breast tumors. PMID- 8432026 TI - Production of recombinant androgen receptor in a heterologous expression system. AB - To facilitate detailed studies of androgen receptor, we have produced a full length receptor protein and some of its deletion mutants in Spodoptera frugiperda (Sf9) insect cells, using the baculovirus expression system. Recombinant baculovirus DNA-infected Sf9 cells expressed these proteins in very high quantities, which represented as much as 30-40% of total insect cell protein at 72 h after infection. Only < 1% of the recombinant protein was soluble in low salt buffers; the majority formed electron-dense cytoplasmic aggregates 30-40 nm in diameter. These aggregates could be solubilized in 6 mol/L guanidine HCl, and biologically active receptor was generated by diluting the guanidine HCl preparation 20- to 50-fold. The full-length receptor, expressed either in a soluble or aggregated form, had characteristics typical of a native receptor: it bound steroids with high affinity and specificity, interacted with DNA in a sequence-specific fashion, and was recognized by domain-specific receptor antibodies. Androgen-receptor protein purified to homogeneity in guanidine HCl required the presence of Zn2+ ions during the refolding to reconstitute its DNA binding form; ZnCl2 was not, however, needed to restore the receptor's steroid binding activity. PMID- 8432027 TI - c-myc oncogene expression in estrogen-dependent and -independent breast cancer. AB - We demonstrate that c-myc gene expression is essential for growth of breast cancer cells. It also plays an important role in the progression of human breast cancer. c-myc gene amplification may be important for cancer cell invasion, but perhaps not essential for nodal metastasis. We also provide compelling evidence that the c-myc oncogene is an estrogen target gene in hormone-responsive breast cancer. Hormonal progression of breast cancer could be brought about by the enhanced expression of the c-myc gene, with gene amplification and enhanced c-myc mRNA stability being two major mechanisms involved. PMID- 8432028 TI - Programming events in the regulation of cell proliferation and death. AB - In developing new and more successful therapies for preventing and treating cancer, it is critical to understand what normally regulates cell proliferation and cell death and what are the specific dysfunctions associated with these regulations in individual cancers. Here we review the programmed series of molecular, cellular, and biochemical events required for a cell's entrance and progression through the proliferative vs death processes as a starting point for such approaches to new therapies. PMID- 8432029 TI - A rapid, automated method for glycohemoglobin. PMID- 8432030 TI - Hitachi 736 chloride bias with abnormal bicarbonate. PMID- 8432031 TI - 1,3-Dichloropropanol-(2) as an indicator of exposure to epichlorohydrine. PMID- 8432032 TI - Nifedipine may cause falsely increased spectrophotometric values of urinary vanillymandelic acid. PMID- 8432033 TI - Free triiodothyromine as a prognostic indicator. PMID- 8432035 TI - Multianalyte testing. PMID- 8432034 TI - The reference range as a control. PMID- 8432036 TI - Analytical interferences from calcium dobesilate in five serum assays. PMID- 8432037 TI - A possible interpretation for difference in neostigmine-induced changes of spontaneous activities and evoked muscle potentials between rat medial gastrocnemius and soleus muscles. AB - 1. Under urethane-anaesthesia, changes of spontaneous activities and evoked muscle potentials in rat medial gastrocnemius (MG) and soleus (SOL) muscles induced by the injection of neostigmine were investigated. 2. Before the administration of neostigmine, spontaneous activities were rarely observed and muscle potentials evoked by single shocks were simply biphasic in both MG and SOL muscles. When the anti-cholinesterase drug was applied, spontaneous discharges of motor units were often observed in bursts in the MG muscles, in contrast to single spikes in the SOL muscles. The biphasic wave of evoked potentials in the MG muscles was followed by one or more oscillations, which were scarcely observed in the SOL muscles. These burst discharges and oscillations in the MG muscles [corrected] also occurred even after transection of the sciatic nerve proximal to the stimulating site. 3. A late component with a small amplitude could be observed in the evoked potentials of MG and SOL muscles. It was potentiated in amplitude after the administration of the drug. 4. Prolonged action of acetylcholine (ACh) has been known to occur in the presence of anticholinesterase drugs, and this was taken into account for the mechanism of the phenomena proposed in the present study. Contrasting changes between MG and SOL muscles were observed, which may be explained by different modes of ACh release in the MG and SOL muscles. PMID- 8432038 TI - Sensitivity of propranolol elimination to hypoxia in the isolated perfused rat liver preparation. AB - 1. The relationship between the hepatic elimination of propranolol and hepatic oxygen delivery was examined in the single-pass isolated perfused rat liver preparation. Varying rates of oxygen delivery were produced (1.35-8.10 mumol/min per g liver) by equilibrating the perfusate with O2/N2 mixtures. 2. In two experiments, in which the rate of oxygen delivery was increased or decreased within the hypoxic range (< 4-5 mumol/min per g liver) every 5 min for 120 min, propranolol clearance responded very rapidly in the same direction as the change in oxygen delivery. 3. In five experiments, propranolol clearance, measured at steady state during an initial 30 min normoxia phase and three subsequent 30 min hypoxia phases (oxygen delivery in the range 1.35-5.89 mumol/min per g liver), was linearly related to hepatic oxygen delivery and consumption (r = 0.92 +/- 0.07). 4. These data, combined with those from six further experiments that used one normoxia phase followed by one hypoxia phase, showed that there was a threshold for oxygen delivery of about 6 mumol/min per g liver, below which propranolol clearance decreased with decreasing oxygenation. 5. This study shows that in the intact liver propranolol elimination is very sensitive to hepatic oxygen supply, with impairment in clearance occurring at the lower limit of what is considered normal hepatic oxygenation in the rat. PMID- 8432039 TI - Renin and prorenin in reproductive tissues during gestation in pigs and cattle. AB - 1. High concentrations of prorenin and active renin were previously found in ovarian follicular fluid from cattle but not from pigs. In the present study female reproductive tissues and fluids from cattle and pigs during gestation were investigated to clarify a possible species difference in active renin and prorenin concentrations. 2. Very high concentrations of active renin but no prorenin were found in corpus luteum from both species. 3. Relatively low concentrations of active renin, in the same order as in maternal blood plasma, were found in myometrium, endometrium, placenta and fetal membranes from both species. Prorenin was undetectable in these tissues except for bovine myometrium and porcine endometrium in some animals. 4. The concentrations of active renin and prorenin in amnionic fluid from both species were below the maternal plasma values. In allantoic fluid the concentrations were higher than in amnionic fluid. 5. The plasma concentrations of active renin and prorenin did not change during gestation in pigs. This finding is in contrast to the observations in humans and does not support a systemic effect of prorenin during gestation. 6. The presence of renin in the reproductive tissues, especially the very high concentrations in the corpus luteum, indicates a local function of the renin-angiotensin system during gestation. PMID- 8432040 TI - Effects of anaesthesia on the removal from plasma of intravenously injected chylomicron-like lipid emulsions in rats and mice. AB - 1. In order to find an anaesthesia with minimum perturbation to the metabolism of chylomicrons, the effects of seven different anaesthetic agents on clearance from plasma of chylomicron-like emulsions were compared. 2. Avertin, urethane, fentanyl, and a ketamine/xylazine mixture all slowed the removal from plasma of emulsion triolein and cholesteryl oleate. The steroid anaesthetic althesin slowed the clearance of emulsion cholesteryl oleate without affecting the removal from plasma of emulsion triolein. Nembutal when injected intravenously at a hypnotic dose did not affect the clearance of emulsion triolein or cholesteryl oleate, whereas at the anaesthetic dose, nembutal slowed the clearance rate of both labelled lipids. 3. Except for althesin, which did not affect the plasma clearance of triolein, fractional clearance rates of emulsion triolein and cholesteryl oleate calculated from blood samples taken during 12 min after injection were significantly slower in the anaesthetized groups compared with controls. However, with avertin, althesin, nembutal and ketamine/xylazine, amounts of radiolabelled triolein and cholesteryl oleate remaining in plasma 25 and 30 min after injection were comparable with the control. Radioactive lipids in plasma remained much higher in rats treated with urethane and fentanyl fluanisonium even 30 min after injection. 4. Avertin was simple to administer and produced a suitable depth of anaesthesia for minor surgery, tail vein injections and blood sampling, whereas althesin and the ketamine/xylazine mixture required supplementary doses to maintain anaesthesia towards the end of the experiment. We concluded that anaesthesia is best avoided for studies of chylomicron clearance. Avertin is the preferred agent if anaesthesia must be used, for example in newborn rats or in mice. PMID- 8432041 TI - Analgesic activity of certain flavone derivatives: a structure-activity study. AB - 1. Flavone, its methoxy derivatives and flavanone were synthesized by standard methods and were tested for analgesic activity in mice by employing acetic acid writhing and tail flick methods. 2. All the tested compounds except flavanone exhibited significant dose-dependent analgesic activity in both the assay models. Some of the compounds were found to involve opioid mechanisms in their analgesic effect. 3. A definite structure-activity relationship was observed in the analgesic activity of flavone derivatives as well as in their mechanism of action. PMID- 8432042 TI - A simple method for estimating 24 h urinary sodium and potassium excretion from second morning voiding urine specimen in adults. AB - 1. An assessment was made of the extent sodium (Na) and potassium (K) intake can be estimated from Na, K and creatinine (Cr) content of a second morning voiding urine (SMU) specimen collected within 4 h after the first voiding upon awakening but before breakfast in 159 clinically healthy, free-living individuals (20-79 years). The SMU and the rest of 24 h urine specimens for a 3-5 day period were collected. 2. The following equations for estimating 24 h urinary Na (24HUNaV) and K (24HUKV) excretions were developed, and the accuracy and the reliability of these equations were evaluated. Estimated value of 24HUNaV (mEq/day) = 16.3 square root of XNa; estimated value of 24HUKV (mEq/day) = 7.2 square root of XK, where XNa (or XK) = SMUNa (or SMUK)/SMUCr x predicted 24 h urinary Cr excretion. 3. Highly statistically significant correlations were detected between the values estimated and measured for both Na (r = 0.728, P < 0.001, n = 159) and K (r = 0.780, P < 0.001, n = 159). 4. These equations were applied to Group 1 subjects, who collected the urine for a single day, and to Group 2, for 3 days. The correlation coefficients between the values estimated and measured for Na and K were 0.531 and 0.443 in Group 1, and 0.821 and 0.590 in Group 2, respectively. No statistically significant differences were observed. 5. The SMU specimens provide a satisfactory alternative to both 24HUNaV and 24HUKV in adults for extensive epidemiological surveys but also for clinical application. PMID- 8432043 TI - Cyclosporine, tolerance, and autoimmunity. AB - A large number of studies have documented the effects of CsA on immunologic tolerance. Initially, these studies concentrated on the ability of CsA to induce tolerance to allografts, particularly in rats. However, it has become apparent that CsA can sometimes block the induction of tolerance, and provoke or aggravate specific autoimmune diseases in several species (Table 1). CsA can inhibit at least three processes thought to contribute to tolerance (Table 2). In the thymus, CsA has been reported by some investigators to block negative selection, but surprisingly, large numbers of undeleted or "forbidden" T-cells are rarely observed in the periphery. In mature T-cells (extrathymic), CsA can block the induction of anergy which occurs after immunization with superantigens, and in vitro this drug can block anergy induction in Th1 clones which occurs when antigenic peptides are presented by metabolically inactive (treated with a fixative) antigen-presenting cells. However, CsA can also enhance the deletion of peripheral superantigen-reactive T-cells, when the drug is administered at high doses. Thus, responses to superantigens can be either enhanced or inhibited depending on the protocol of CsA administration. Whether or not these phenomena apply to conventional antigens has not been determined. Numerous studies demonstrate that CsA treatment can either enhance or depress suppressor T-cell function in various experimental models. The interpretation of data on suppressor cells is complicated by the current poor understanding of the function of the cells. In CsA-induced syngeneic (or autologous) GVHD, CsA may inhibit both T-cell anergy induction and the generation and/or function of suppressor cells. CsA can alter Th1/Th2 antagonism, such that DTH responses are enhanced. Enhanced Th1 activity could explain the deterioration that CsA sometimes provokes in autoimmune diseases where DTH is important, e.g., collagen-induced arthritis and EAE. CsA can prevent the development of neonatal tolerance. The latter effect may account, at least in part, for the induction of organ-specific autoimmunity observed after treating mice with CsA during the neonatal period. However, in all the situations mentioned the effects of CsA on tolerance cannot be easily explained by a single mechanism. There is redundancy in the immune tolerance mechanism, such that clonal deletion, clonal anergy, and suppressor cells may all be capable of maintaining tolerance to similar antigens. Thus, it is likely that CsA must inhibit more than one of these mechanisms for autoimmunity to occur.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8432044 TI - Immunologic detection of phosphatidylserine externalization during thrombin induced platelet activation. AB - The antiphospholipid antibody syndrome is characterized by circulating antiphospholipid antibodies against cardiolipin (CL) and phosphatidylserine (PS) and clinically associated with a high risk of spontaneous thrombosis. Three monoclonal antibodies that differentiate between CL or PS were tested against resting and thrombin-activated platelets by flow cytometry. Each antibody reacted differently with CL and PS; 3SB9b reacted with PS, D11A4 reacted with CL, and BA3B5C4 reacted with both CL and PS. Activated platelets bound BA3B5C4 and 3SB9b, but not D11A4. The BA3B5C4-reactive epitope appeared earlier during activation than the epitope reactive with 3SB9b. These data suggest that antibodies against PS are reactive with activated platelets and that two immunoreactive forms of PS are sequentially expressed on platelets during activation. PMID- 8432045 TI - Hairy cells from hairy cell leukemia patients presenting with pronounced polyclonal hypergammaglobulinemia secrete a factor enhancing IgG synthesis. AB - We studied the immunological function of hairy cells from hairy cell leukemia (HCL) patients presenting with pronounced polyclonal hypergammaglobulinemia (PPH). Hairy cell conditioned medium (HCCM) obtained from HCL patients with PPH augmented IgG production by normal peripheral blood mononuclear cells in a dose dependent fashion, while HCCM from patients without PPH had no effect on IgG production. HCCM from the patients with PPH failed to enhance IgG synthesis by T cell-depleted mononuclear cells. Separation of T and B cells by a 0.4-microns membrane as well as monoclonal antibodies to HLA-DR and CD3 molecules prevented HCCM-dependent IgG synthesis. No B cell growth factor activity, interleukin-1, or interleukin-6 was detected in the HCCM. On examination by fractionation of the HCCM, IgG-inducing activity was detected in the fractions of 5000 to 8000 Da. These results indicate that hairy cells from HCL patients with PPH secrete a factor inducing IgG synthesis, and that the induction of IgG synthesis by the factor requires T-B cell interactions involving T cell receptor/CD3 complex and MHC class II antigens. This factor may play an important role in the development of PPH. PMID- 8432046 TI - Control of IgE responses. III. IL-6 and IFN-alpha are isotype-specific regulators of peak BPO-specific IgE antibody-forming cell responses in mice. AB - The ability of cytokines (IL-4, IL-5, IL-6, IFN-alpha, IFN-gamma, TNF-alpha, GmCSF) to regulate peak benzylpenicilloyl (BPO)-specific IgE antibody-forming cell (AFC) responses was investigated. These responses were induced in BALB/c mice by ip injection of BPO-keyhole limpet hemocyanin (BPO-KLH; 10 micrograms) in aluminum hydroxide gel on Days 0, 21, and 42. On Day 44, or on Days 43, 44, and 45, mice were injected sc with varying doses of cytokine or anti-cytokine antibody. On Day 46, the numbers of BPO-specific AFC (IgM, IgG1, IgE and IgA) in spleen were determined ex vivo in enzyme-linked immunosorbent spot assay. Among the cytokines tested, only IL-6 suppressed BPO-specific IgE AFC responses in an isotype-specific fashion (60-90%). However, treatment of mice with anti-IL-6 also suppressed these responses, suggesting that IL-6 can either suppress or increase peak antigen specific IgE responses, depending upon its concentration. Among the cytokines tested, only IFN-alpha increased BPO-specific IgE AFC responses in an isotype-specific fashion. Since treatment with anti-IFN-alpha suppressed these responses, it appears that IFN-alpha is required to maintain peak antigen specific IgE AFC responses. IL-4 or IFN-gamma nonspecifically suppressed responses of all isotypes. Treatment with anti-IL-4 also suppressed IgE responses, suggesting that this cytokine is required to maintain peak antigen specific IgE responses. Treatment with anti-IFN-gamma increased IgE responses, indicating that IFN-gamma suppresses peak antigen-specific IgE responses. PMID- 8432047 TI - Elevation of cerebrospinal fluid interleukin-6 activity in patients with vasculitides and central nervous system involvement. AB - The pathogenesis of central nervous system (CNS) involvement in vasculitides remains unclear. We evaluated cerebrospinal fluid (CSF) interleukin-6 (IL-6) activity in relation to the CNS disease activity in vasculitides. Three patients with vasculitides of different categories who showed CNS manifestations were studied, including polyarteritis nodosa, temporal arteritis, and Behcet's disease. All three patients showed marked elevation of CSF IL-6 activity in parallel with the CNS disease activity. In one of the three patients, cerebral vasculitis was demonstrated histologically. All these patients also showed elevation of serum IL-6 activity in parallel with systemic symptoms, such as fever and/or elevation of C-reactive protein and erythrocyte sedimentation rate. These results strongly suggest that elevation of CSF IL-6 activity may underly the common pathogenetic mechanism of CNS involvement of vasculitides irrespective of their category. Taken together with the histopathological findings in one patient, the data also suggest that inflammation might not be restricted within the CNS blood vessels, but rather be extended to brain parenchyma to promote IL-6 production presumably by glial cells. PMID- 8432048 TI - Genetic susceptibility to the induction of murine experimental autoimmune orchitis (EAO) without adjuvant. I. Comparison of pathology, delayed type hypersensitivity, and antibody. AB - In the present study, it was demonstrated that there were marked strain differences in susceptibility to the induction of our new murine model of experimental autoimmune orchitis (EAO; definite orchitis with hypospermatogenesis) induced by two or three sc injections with viable syngeneic testicular germ cells (TC) without any adjuvants. Among 12 inbred strains of mice examined, the A/J (H-2a), C3H/He (H-2k), and C3H/HeN (H-2k) strains were highly susceptible, whereas the C57BL/6N (H-2b), C57BL/10Sn (H-2b), BALB/cAnN (H-2d), AKR/N (H-2k), CBA/JN (H-2k), C3H/HeJ (H-2k), and MRL/lpr (H-2k) strains were low susceptible, and the DBA/2N (H-2d) as well as C3H/BiKi (H-2k) strains were resistant. In particular, mice of the H-2k haplotype demonstrated varying degrees of susceptibility, from highly to totally resistant, to the induction of EAO. Disease susceptibility to this type of EAO does not seem to be associated with a particular H-2 haplotype. All mice of the highly susceptible strains that received two injections of TC (TC x 2) developed a significant increase in both levels of delayed footpad reaction (DFR) to TC and anti-TC antibodies measured by ELISA. In the low susceptible and the resistant strains receiving TC x 2 or TC x 3, there was no correlation between the immune responses and the susceptibility to disease in these strains, with the exception of the BALB/cAnN mice receiving TC x 3. The low susceptible and the resistant mice that received TC x 2 were classified into four groups based on the DFR and antibody response: the C57BL/6N, BALB/cAnN, CBA/JN, and C3H/HeJ strains were both positive, and the C57BL/10Sn and AKR/N strains were both negative or very low; the DBA/2N and MRL/lpr strains showed negative DFR and positive antibody response, and the C3H/BiKi strain showed quite the opposite. Almost all mice of the 12 inbred strains that received TC x 3 showed positive antibody response, although its level varied. There seems to be no linkage between the cell-mediated and humoral immune responses and the H 2 locus in our new EAO model. PMID- 8432049 TI - Genetic susceptibility to the induction of murine experimental autoimmune orchitis (EAO) without adjuvant. II. Analysis on susceptibility to EAO induction using F1 hybrid mice and adoptive transfer system. AB - In our novel murine model of experimental autoimmune orchitis (EAO) induced by two or three injections of viable syngeneic testicular germ cells (TC) alone, significant differences in susceptibility to the induction of EAO were found, and the disease susceptibility did not seem to be associated with a particular H-2 haplotype. The H-2 identical background disparate (highly susceptible x low susceptible)F1 hybrids, (C3H/He x C3H/HeJ)F1 and (C3H/HeJ x C3H/He)F1 mice, were highly susceptible to the induction of EAO. The H-2 identical background disparate (highly susceptible x resistant)F1 hybrids, (C3H/He x C3H/BiKi)F1 and (C3H/BiKi x C3H/He)F1 mice, were low susceptible to the induction of EAO. Both the H-2 and background disparate (highly susceptible x resistant)F1 hybrids, (C3H/He x DBA/2N)F1 and (DBA/2N x C3H/He)F1 mice, were equally resistant to EAO induction. In the susceptible hybrids, both delayed footpad reaction (DFR) and antibody responses to TC increased. On the other hand, in the resistant hybrids, the levels of anti-TC antibodies were elevated but the DFR to TC remains depressed. This suggests that the antibody production and induction of DFR may be under different genetic controls and that cellular immunity plays an important role in this EAO induction. In order to search for the mechanistic basis for low susceptible C3H/HeJ and resistant C3H/BiKi mice, these mice received orchitis inducible spleen cells (SPCs) from C3H/He mice. C3H/HeJ mice were highly susceptible to passive EAO. In contrast, disease-resistant C3H/BiKi mice failed to develop passive EAO. In addition, we examined whether or not regulatory cells capable of preventing the disease induction were generated in low susceptible C3H/HeJ and resistant C3H/BiKi mice immunized with TC. Transfer of SPCs from TC immunized C3H/HeJ and C3H/BiKi mice into C3H/He mice before the EAO challenge had no suppressive effect on subsequent disease induction. PMID- 8432050 TI - Marked improvement in left ventricular systolic function 3 months after cessation of excess alcohol intake. AB - Excessive alcohol ingestion is a recognized cause of reversible dilated cardiomyopathy. A case is reported of dilated cardiomyopathy associated with excessive alcohol consumption that was remarkable with respect to the rapidity and extent of normalization in left ventricular systolic function after cessation of alcohol consumption. PMID- 8432051 TI - Tc-99m HMPAO cerebral scintigraphy. A reliable, noninvasive method for determination of brain death. AB - To determine the usefulness of cerebral blood flow imaging for the diagnosis of brain death, 4 female and 12 male patients, aged 19 to 69 years and suffering from various intracranial lesions, were studied. In addition to neurologic examination, electroencephalographic recording, and cerebral angiography, tomographic brain scintigraphy was performed using a SPECT system with a LEAP collimator after the intravenous administration of 555 MBq Tc-99m HMPAO. The radioisotopic scanning procedure revealed no intracranial perfusion in 14 of the 16 patients. Only minimal cerebellar blood flow was seen in one patient. In another, residual right-sided supratentorial flow was initially present but absent in a follow-up HMPAO SPECT. Carotid angiography (four-vessel contrast media angiography) confirmed the above results without exception. Because HMPAO is taken up by normal brain tissue with no significant redistribution for several hours, the tracer is particularly helpful in cases of suspected brain death. The quality of the tracer must be established by chromatography. Interpretation of the SPECT images produces reliable and reproducible results. In conclusion, cerebral blood flow imaging with HMPAO is a safe, noninvasive procedure for the determination of brain death, that produces fast, reliable, reproducible, and easy-to-interpret results. PMID- 8432052 TI - Using the radionuclide salivagram to detect pulmonary aspiration and esophageal dysmotility. AB - That the radionuclide "milk" scan is insensitive for aspiration has been demonstrated. Here the authors review their experience with the radionuclide salivagram in its ability to detect aspiration in children. Tc-99m sulfur colloid, 0.5 to 1.0 mCi in less than 1 mL, is instilled into the mouth and sequential supine posterior images of the thorax are obtained for an hour with delayed images until the oropharynx is cleared of radiotracer. Fourteen studies have been performed in 13 patients aged 1 month to 6.5 years. There are scintigraphic findings consistent with aspiration in 4 of 14 studies (28%); dysmotility (prolonged retention of activity in the esophagus) in 7 of 14 studies (50%); and normal studies in 3 of 13 patients (22%). Eight of 13 patients had milk scans; all were negative for aspiration. One patient studied twice had aspiration on the first examination, and dysmotility on the second study. It is concluded that the salivagram can detect aspiration of oral secretions, is superior to the milk scan in detecting aspiration, and can demonstrate esophageal dysmotility. PMID- 8432053 TI - Extensive salivary contamination due to concurrent use of chewing tobacco during I-131 radioablative therapy. AB - Although multiple authors have reported on various causes of external I-131 contamination after administration of radioiodine, to the authors' knowledge there have been no reported cases of external contamination from salivary secretions due to expectoration of chewing tobacco. A case of extensive I-131 contamination of a hospital room, furniture, and plumbing due to indiscriminate use of chewing tobacco during an inpatient I-131 radioablative therapy is presented. PMID- 8432054 TI - Ga-67 scintigraphy in pulmonary blastoma in a child. AB - Pulmonary blastoma is a rare primary malignancy of the lung with a small number of cases reported in children. The primary treatment is surgery, however radiotherapy and chemotherapy are also used. The ability to determine whether the tumor has been fully removed and when recurrence occurs is important for appropriate treatment and prognosis. A case of a 7-year-old girl with pulmonary blastoma is reported in which the primary tumor is extremely Ga-67-avid and in which the gallium scans were helpful in determining early recurrence and metastatic disease to the brain. PMID- 8432055 TI - Pulmonary alveolar proteinosis. Xe-133 scintigraphic findings before and after bronchopulmonary lavage. AB - A 44-year-old woman with pulmonary alveolar proteinosis was treated by repeated unilateral bronchopulmonary lavages over 6.5 years. The effectiveness of the treatment was assessed by Xe-133 scintigraphy as well as lung function tests and chest roentgenograms. Xe-133 scintigraphy clearly demonstrated improvement of regional ventilation and perfusion, and equalization of the ventilation and perfusion ratio. Therefore, Xe-133 scintigraphy was found to be useful in the analysis of changes in regional aeration, ventilation, and perfusion before and after bronchopulmonary lavage in pulmonary alveolar proteinosis. PMID- 8432056 TI - Ga-67 scintigraphy after bone marrow harvest. Significance of "sacroiliac" asymmetry in the lymphoma patient. AB - The importance of recognizing asymmetric Ga-67 citrate uptake in the sacroiliac region after bone marrow harvest and transplant is discussed in a case of non Hodgkin's lymphoma. The patient underwent chemotherapy, irradiation, and autologous bone marrow transplant for stage IV disease. Ga-67 scintigraphy revealed sacroiliac asymmetry suggesting medial iliac reparative changes after bone marrow harvest. Iliac bone marrow biopsy showed no evidence of infection or of recurrent tumor. Subsequent follow-up imaging and open biopsy demonstrated lymphomatous invasion of adjacent soft tissue where initial findings were thought to represent benign, postharvest changes. PMID- 8432057 TI - Diagnosis of diabetic gastroparesis on Tc-99m hepatobiliary scintigraphy. AB - Diabetic gastroparesis is a common problem in diabetics, especially insulin dependent diabetics. The diagnosis usually is suggested on plain radiographs and confirmed on either upper gastrointestinal barium series or radionuclide gastric emptying studies. The clinical diagnosis is not always easy and some patients may present atypically with right upper quadrant pain simulating acute cholecystitis. In these patients, hepatobiliary scintigraphy may be the initial investigation performed and may first demonstrate unsuspected gastroparesis. Therefore, it is useful for the nuclear medicine physician to be aware of this entity to ensure early diagnosis and prompt treatment. The authors report one such case of diabetic gastroparesis that was diagnosed initially on a Tc-99m hepatobiliary scan. PMID- 8432058 TI - Bone scan findings in craniometaphyseal dysplasia. AB - Craniometaphyseal dysplasia is a rare genetic bone disorder characterized by undertubulation of the long bones, especially in the lower extremities, and sclerosis of the skull base. Differentiation from other sclerosing bone dysplasias, including metaphyseal dysplasia (Pyle's disease), craniodiaphyseal dysplasia, and diaphyseal dysplasia is based largely on characteristic radiographic findings. Radionuclide bone scans usually are not necessary for diagnosis, but are helpful in demonstrating the abnormal bone metabolism. The authors report the first whole-body bone images in a patient with craniometaphyseal dysplasia, demonstrating the abnormal bone activity over time. PMID- 8432059 TI - Splenic and partial hepatic necrosis after vascular occlusion. AB - A 74-year-old woman underwent two operations to correct an aortoduodenal fistula and to have an axillofemoral bypass graft inserted; these required temporary vascular occlusion. Her hepatic function test results began deteriorating. Initial and follow-up Tc-99m sulfur colloid studies revealed activity in the kidneys, consistent with disseminated intravascular coagulation. There was significant radiocolloid in the bone marrow and lungs, suggesting severe hepatic dysfunction. The spleen was not demonstrable on dynamic images or static views. In addition, there was a significant lateral hepatic defect, with a "lung overlap." The splenic lack of function and the hepatic lesion were due to necrosis (demonstrable on CT imaging), likely related to the prior vascular clamping. PMID- 8432060 TI - Tc-99m isonitrile uptake in a brain metastatic lesion. Comparison with Tc-99m DTPA using planar and SPECT imaging. AB - Tc-99m isonitrile uptake in a metastatic brain tumor is demonstrated using planar and SPECT imaging. Comparison with Tc-99m DTPA shows a different distribution pattern and uptake intensity, suggesting a different mechanism for both tracers. It is possible that Tc-99m CPI could reflect metabolic activity of the tumor cells and might be useful to evaluate the grade of malignancy as well as the recurrence of brain tumors. PMID- 8432061 TI - Pseudodislocation of the glenohumeral joint diagnosed by bone scintigraphy. PMID- 8432062 TI - Marked bladder displacement by dilated rectosigmoid colon. PMID- 8432063 TI - Complications of laparoscopic cholecystectomy. PMID- 8432064 TI - Abnormal bone scintigraphy before clinical symptoms in a patient with defective phagocyte function. PMID- 8432065 TI - Gallium scintigraphy in hemodialysis access graft infection. PMID- 8432066 TI - The use of Xenon-133 ventilation scan performed immediately after Tc-99m MAA perfusion scan. PMID- 8432067 TI - A false positive space-occupying lesion appearance in colloid liver scintigraphy due to Chilaiditi's syndrome. PMID- 8432068 TI - Thyroid hemiagenesis by I-123 thyroid scan with high-resolution real-time ultrasound confirmation. PMID- 8432069 TI - A case of extraosseous uptake with bone scintigraphy of angiolipoma masses. PMID- 8432070 TI - Malignant pheochromocytoma. Diffuse skeletal metastases manifested by I-123 metaiodobenzylguanidine scintigraphy. PMID- 8432071 TI - Pulmonary edema in an infant following passive inhalation of free-base ("crack") cocaine. PMID- 8432072 TI - Neuropsychiatric toxicity of phenytoin. Importance of monitoring phenytoin levels. PMID- 8432073 TI - Newborn identification. Compliance with AAP guidelines for perinatal care. PMID- 8432074 TI - Clinical predictors of catheter use following implantation of intravenous access devices in cystic fibrosis patients. PMID- 8432075 TI - Bone lesions in Langerhans cell histiocytosis. PMID- 8432076 TI - Elevated phenylalanine concentrations in benign hyperphenylalaninemia from evaporated milk feedings. PMID- 8432077 TI - Pathologic laughter in children. PMID- 8432078 TI - Pneumocystis carinii pneumonia preceding childhood lymphoma. PMID- 8432079 TI - Recurrent parotitis in childhood. PMID- 8432080 TI - Dorsal penile root anesthesia for circumcision. PMID- 8432081 TI - Physicians' attitudes toward the diagnosis and management of fever in children 3 months to 2 years of age. AB - Ninety-seven primary-care physicians, including 73 family physicians and 24 pediatricians, were surveyed in order to ascertain their knowledge and attitudes regarding fever in children 3 months to 2 years of age. A rectal temperature between 37.0 degrees C and 37.9 degrees C was considered to indicate fever by 35% of physicians. Only 17% believed there was no danger from fever, while 12% believed that fever could cause brain damage. Seizures were considered a principal danger of fever by 49% of physicians, and 22% believed that brain damage could result from typical febrile seizures. While 70% chose relief of discomfort as the main purpose of antipyretic treatment, 30% would use temperature alone as an indication for antipyretics. It is concluded that although many physicians have an acceptable attitude toward the diagnosis and management of fever, a significant number still have exaggerated concerns. PMID- 8432082 TI - Family experiences, attitudes, and household safety practices regarding firearms. AB - To assess families' experiences with shootings and firearm ownership and attitudes, 208 children aged 5 to 12 years were interviewed and 242 parents filled out a questionnaire, all at an urban hospital. Forty-three percent of the parents and 25% of the children had personal knowledge of shootings. Of the parents, 10% owned guns, of which only 21% were stored safely. Gun ownership was more common in homes with resident adult males (14%) than in those with no adult males (3%). Most children (81%) played with guns, and 20% to 25% preferred violent TV shows, games, and toys. Parents' and children's attitudes toward firearms and children's gun play did not differ by level of mother's education; method of payment for, or site of, health care; income; or exposure to shootings. Children with personal knowledge of shootings more often expressed fears of being shot than did other children (52% vs 31%). The children in our study population were similar in their gun play and attitudes about gun use despite disparate socioeconomic backgrounds and exposure to shootings. PMID- 8432083 TI - Evaluation of cavernous transformation of the portal vein by magnetic resonance imaging. AB - We describe two children who underwent magnetic resonance imaging (MRI) as part of the evaluation of isolated splenomegaly after Doppler ultrasound was unable to identify the portal vein. The diagnosis of cavernous transformation of the portal vein and the normalcy of the biliary tract and hepatic architecture were confirmed by MRI. Because of the risks associated with computed tomography (CT) and angiographic evaluation of such patients, the use of MRI, a noninvasive modality, in the evaluation of pediatric patients requires further consideration. PMID- 8432084 TI - Indications and application of epidural anesthesia in a pediatric population outside the perioperative period. AB - The techniques of spinal and epidural anesthesia have been key components of anesthetic care for the past 100 years. Although commonly used in the operating room, their use in children outside the perioperative period has been limited. The author presents his experience with the use of epidural anesthesia to provide analgesia in five children when parenteral narcotics were ineffective in treating pain associated with burns, sickle cell crisis, trauma, and malignancies. Additionally, the principles and adverse effects of epidural anesthesia are discussed. PMID- 8432085 TI - Reevaluating the impact of video games. AB - The evolution of the video game phenomenon is reviewed and contemporary data are presented. A survey assessing frequency and location of play and game preference was completed by 357 seventh- and eighth-grade students. In this middle-class sample, about two thirds of girls played video games at least one to two hours per week at home, but only 20% played in arcades. About 90% of boys played in the home and about 50% in arcades. Approximately half of preferred games were from one of two categories of violent games, while 2% of preferred games were educational. Parent education about the influence of the media should include recommendations to monitor game playing and influence game selection. PMID- 8432086 TI - Prevalence and characteristics of Blastocystis hominis infection in children. AB - Blastocystis hominis, a protozoan whose pathogenicity has been questioned, is sometimes found in the human gastrointestinal tract. We sought to determine the prevalence of Blastocystis in stool and to characterize clinical features of infection with Blastocystis in children. Forty-six (3%) of 1,736 patients undergoing fecal microscopy at Children's Hospital of Pittsburgh between January 1, 1985, and December 31, 1988, harbored Blastocystis. Of these 46 children, 75% had exposure to well water or had been in developing countries. Thirty-nine of the 46 (85%) experienced gastrointestinal symptoms, such as abdominal pain, diarrhea, vomiting, and weight loss. Blastocystis was the only parasite found in 35 of those 39 symptomatic children. Symptoms resolved within one month in 90% of patients receiving antiparasitic pharmacotherapy, but in only 58% (P < .04) of those receiving no therapy. We conclude that children infected with Blastocystis often experience gastrointestinal symptoms and that treatment increases the rate of symptomatic improvement. We speculate that Blastocystis is a human pathogen. PMID- 8432087 TI - Keeping ahead of childhood asthma. PMID- 8432088 TI - 94th Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics. Honolulu, Hawaii, March 24-26, 1993. Abstracts. PMID- 8432089 TI - Children are in control. AB - We argue on the basis of recent experimental results that modular principles of universal grammar (UG) play a continuous role in the first language acquisition of control. Our results involve both comprehension and production data from 108 3 to 8-year old children who are acquiring English. The results provide evidence against the hypothesis that there is a "stage" at which children do not know fundamental grammatical principles of control, or fail to apply the basic structural analysis relevant to control. We suggest that previous proposals for this hypothesis have been misled by (1) attention to only one aspect of the knowledge of control, namely choice of antecedent in comprehension of the embedded null subject in these structures and (2) misinterpretation of the nature of the principle by which children overgeneralize the choice of object as antecedent in control structures. Although the new results do replicate delay in acquisition with the unique subject-control verb "promise", they suggest that this delay is caused by a need to integrate modular principles of UG with language-specific principles by which the lexicon and syntax (constituent structure and case) are related. The overgeneralization of choice of object as antecedent is shown to reflect a continuous principle of syntactic minimality. PMID- 8432090 TI - Negative evidence in language acquisition. AB - Whether children require "negative evidence" (i.e., information about which strings of words are not grammatical sentences) to eliminate their ungrammatical utterances is a central question in language acquisition because, lacking negative evidence, a child would require internal mechanisms to unlearn grammatical errors. Several recent studies argue that parents provide noisy feedback, that is, certain discourse patterns that differ in frequency depending on the grammaticality of children's utterances. However, no one has explicitly discussed how children could use noisy feedback, and I show that noisy feedback is unlikely to be necessary for language learning because (a) if noisy feedback exists it is too weak: a child would have to repeat a given sentence verbatim at least 85 times to decide with reasonable certainty that it is ungrammatical; (b) no kind of noisy feedback is provided to all children at all ages for all types of errors; and (c) noisy feedback may be an artifact of defining parental reply categories relative to the child's utterance. For example, because nearly all parental speech is grammatical, exact repetitions (verbatim repetitions of child utterances) necessarily follow more of children's grammatical utterances than their ungrammatical utterances. There is no evidence that noisy feedback is required for language learning, or even that noisy feedback exists. Thus internal mechanisms are necessary to account for the unlearning of ungrammatical utterances. PMID- 8432091 TI - On theories of belief bias in syllogistic reasoning. PMID- 8432092 TI - Reconstructive remembering of the scientific literature. AB - In this paper we investigate the role of reconstructive memory in citation errors that occur in the scientific literature. We focus on the case of de Groot's (1946) studies of the memory for chess positions by chess experts. Previous work has shown that this research is very often cited incorrectly. In Experiment 1 we show that free recall of this work by research psychologists replicates most of the errors found in the published literature. Experiment 2 shows that undergraduates reading a correct account of the de Groot study also make the same set of errors in recall. We interpret these findings as showing that consistent errors in secondary accounts of experimental findings are frequently reconstructive memory errors due to source confusion and schema-based processes. Analysis of a number of other examples of scientific literature that have been frequently cited incorrectly add additional support to the reconstructive account. We conclude that scientists should be aware of the tendency of reconstructive memory errors to cause violations of the scientific norm of accurate reporting of the scientific literature. PMID- 8432093 TI - When reading is acquired but phonemic awareness is not: a study of literacy in Down's syndrome. AB - The concept of phonological awareness (PA) has loomed large in recent discussions of the acquisition of literacy in alphabetic orthographies (Bryant & Goswami, 1987). The term is usually taken to imply overt knowledge of how spoken words can be analysed into their constituent sounds ("phones"). This awareness is assessed by such tasks as requiring the child to produce (or recognize) rhymes, to indicate how many sounds there are in a particular word, or to delete a constituent (phone or syllable) of a word and pronounce the remainder. It has been asserted that these skills play a causal role in the development of reading ability (Bradley & Bryant, 1983). We provide evidence against the position that such skills are essential prerequisites for reading (and any other hypothesis that claims necessary causal links between reading and PA). It is shown that some children with Down's syndrome can learn to read despite their failure on a set of tasks conventionally employed to assess PA. The pedagogic implication is that reading should be taught by teaching reading skills (including letter-sound correspondences), not phonological awareness skills. PMID- 8432094 TI - Visual imagery and visual-spatial language: enhanced imagery abilities in deaf and hearing ASL signers. AB - The ability to generate visual mental images, to maintain them, and to rotate them was studied in deaf signers of American Sign Language (ASL), hearing signers who have deaf parents, and hearing non-signers. These abilities are hypothesized to be integral to the production and comprehension of ASL. Results indicate that both deaf and hearing ASL signers have an enhanced ability to generate relatively complex images and to detect mirror image reversals. In contrast, there were no group differences in ability to maintain information in images for brief periods or to imagine objects rotating. Signers' enhanced visual imagery abilities may be tied to specific linguistic requirements of ASL (referent visualization, topological classifiers, perspective shift, and reversals during sign perception). PMID- 8432095 TI - Null subjects: comments on Valian (1990) AB - In this paper, I do not claim that any particular parameter-setting approach is correct, or even provide a characterization of subjectless sentences in children's speech. The only point of this paper is to show that Valian's argument that single-value solutions for setting the null subject parameter have insoluble problems is incorrect. Valian is correct that being able to analyze and interpret triggering data is a prerequisite for setting parameters, but a single-value solution of the sort described in this paper (and implicitly assumed in parameter setting acquisition theories) is sufficient to do so; there is no need to invoke the dual-value solution that Valian argues is necessary. Furthermore, I argue that the single-value solution should be preferred on the grounds that (i) the mechanism I propose maintains many of the niceties of idealized parameter-setting acquisition theories whereas Valian's approach explicitly gives up on these attractive features of standard parameter-setting models, and (ii) it follows from dual-value theories but not single-value theories (depending on the nature of parameters and how many parameters there are) that parsing and speech production involve over-whelmingly difficult computations for children. PMID- 8432096 TI - Determinants of variation in dental caries experience in primary teeth of Hong Kong children aged 6-8 years. AB - A representative sample of Hong Kong children aged 6-8 yr was examined for dental caries, and data on possible explanatory variables for dmft were obtained from questionnaires. Variation in dmft was partially accounted for by the effect of some demographic variables and other variables having a socioeconomic base. Girls had a lower dmft index than boys, and being born in Hong Kong rather than elsewhere (that is, China) was also associated with a lower dmft index. Better dental status was strongly associated with increasing educational level of the mother, monthly household income, and with an increasingly positive perception of the questionnaire respondent's own dental status. Preschool dental visits and enrollment in the School Dental Care Service were associated with higher dmft indices. Altogether, 22.5% of the variance in dmft was explained. It was concluded that: 1) demographic and socioeconomic factors significantly affect dmft variation in Hong Kong. 2) the mother's role in determining the dental status of her child is probably important, and 3) further elucidation of the variation in dmft will depend on the analysis of data pertaining to dietary and oral hygiene practices during the preschool years and to an analysis of tooth morphology, fluoride exposure, and microbiologic, salivary, and genetic factors. PMID- 8432097 TI - Prevalence of dental caries and gingivitis in a population of Mexican schoolchildren. AB - The prevalence of dental caries and gingivitis was assessed in schoolchildren of the Tlalpan region in Mexico City. A total of 700 children (age range: 11-17 yr) of both sexes were examined. The sample population included children attending the Middle-School System, where two shifts are run (A.M. and P.M.). Decayed, missing and filled surfaces (DMFS), and Gingival Index (GI) were recorded for all existing teeth. Analysis of the data showed that mean DMFS scores increased with chronological age in both genders, were higher in the P.M. session, and more elevated in females. Similarly the mean GI scores also increased with age, and were higher in the P.M. session. In contrast to the DMFS scores, males presented higher GI scores than females at all age intervals. The results of our study indicated a distinctively high prevalence of caries and gingivitis in Mexican schoolchildren. PMID- 8432098 TI - Prevalence and severity of dental fluorosis in primary schoolchildren in Nairobi, Kenya. AB - The purpose of this study was to assess the prevalence and severity of dental fluorosis in 513 primary school children in Nairobi. The clinical examination was performed in a room with natural daylight using Thylstrup & Fejerskov's index (TFI). Overall, 18% of 6-8-yr-olds had dental fluorosis in the primary dentition and 76% of 13-15-yr-olds in the permanent dentition. There was no significant sex difference (P > 0.05) in either the prevalence or the severity of fluorosis. In children with mixed dentition, the prevalence and severity of fluorosis was higher in the permanent teeth. In the permanent dentition, no clear difference was demonstrable in the severity between the anterior and the posterior teeth. The degree of fluorosis in most of the children in the area served with river water (0.2-0.4 ppm F-) was of a very mild form. However, in the area served with borehole waters, 48% of the children and 40% of the teeth were found to have TFI scores > or = 5. Measures to reduce dental fluorosis are necessary in the latter area. PMID- 8432099 TI - Simulation study of methods to detect periodontal associations when they are inconsistent among subjects. AB - Most statistical methods used to evaluate associations between indices of clinical periodontal diseases and purported prognostic markers test for effects across subjects. If associations exist within only a subset of subjects, however, associations may be masked, particularly in small studies. This issue was explored by using simulation to study four methods for detecting periodontal associations. Built into the simulations was the possible biological reality that a non-zero association between the two variables of interest (squared correlation coefficients, rho 2, ranged from 0.1 to 0.9 depending on simulation), measured at 16 sites per subject, did not exist in all of 10 hypothetical subjects. The four methods for testing the null hypothesis that rho = 0, or a related hypothesis; were: (1) Sites, analysis based on 160 sites incorrectly considered independent observations; (2) Subjects, analysis based on one score for each of 10 subjects; (3) Each subject, separate analyses based on sites within each of 10 subjects, family-wise type I (alpha) error corrected for multiplicity, and (4) the Each Subject method where P-levels were estimated using permutation procedures rather than t-distributions. Each Subject methods were found to have greater relative power (although there are differences in null hypotheses) under conditions of heterogeneity in rho and are considered to be particularly relevant in exploratory periodontal research when the primary interest is establishing the existence of a relationship, even if in only a subset of subjects. PMID- 8432100 TI - An investigation into the use of a voice operated data input system. AB - The aim of this study was to evaluate a voice operated data collection system intended for use in epidemiological surveys. Three groups of 45 adolescents, with similar caries experience, were examined by one examiner in schools. The caries data resulting from these examinations were collected in three ways; keyboard activated input to a portable computer, paper chart recording followed by manual input on return to base and examiner voice activated input direct to the computer. Maximum levels of accuracy were found with all three methods. The quickest method of collection in the field was by paper chart with a mean collection time per subject of 2.59 min, followed by 3.15 min for the manual keyboard method and 4.07 min for the voice activated method. When all the factors affecting time were taken into consideration it was found that overall the manual keyboard method was significantly faster than both the paper chart method and the voice activated method. PMID- 8432101 TI - A radiographic study of dental health in adult patients with dental anxiety. AB - The objective of this study was to compare the dental health in a group of 90 patients with severe dental fear (FP), aged 20-41, with that of a matched control group of ordinary dental patients (OP). All registrations were made from radiographic intraoral full mouth surveys. Mean number of missing teeth among FP and OP patients was 4.4 and 2.5, respectively. On average, FP patients had 19.5 decayed surfaces compared to 7.9 in OP patients. Mean number of filled surfaces was 13.1 and 8.1 in OP and FP patients, respectively. FP patients, on average, had significantly more periradicular bone lesions as well as pronounced marginal bone loss than OP patients. This study showed that dental fear patients in general have a substantially deteriorated dental health compared to ordinary dental patients. Moreover, different dental care habits were evident between FP and OP patients. A progressive severity in dental disease pattern was found among FP patients. PMID- 8432102 TI - Attitudes and perceptions of adults towards orthodontic treatment in an Asian community. AB - A retrospective survey of 358 local Chinese adult orthodontic patients was undertaken to determine the motivating factors behind orthodontic treatment and the discomfort caused by fixed orthodontic appliances. From the completed questionnaires of 203 patients, the principal conclusions were that the improvement in dento-facial aesthetics following orthodontic treatment enhanced their self-confidence and self-esteem in a majority of patients; discomfort in oral soft tissues and teeth were transient and did not exceed 7 days; transient pain from teeth was experienced by 91% of patients and in 39% of these patients the discomfort to teeth was experienced with each new archwire or elastic force application. These results may be useful in relating discomfort levels to prospective orthodontic patients. It was also evident in the study that several cross-cultural differences existed in the attitudes of our patients compared to those reported in Caucasians. PMID- 8432103 TI - A panoramatomographic study of the teeth and jaws of Finnish university students. AB - A random sample of panoramic radiographs was taken of 1027 (386 male and 641 female) university students. All the students were born between 1965 and 1971. The following were examined: caries, apical radiolucencies, endodontically treated teeth, marginal and vertical bone loss, third molars, supernumerary, missing, and persisting teeth, bone structure, condyles, maxillary sinuses and soft tissue calcifications. In the inter- (of two examiners) and intra-examiner variation Kappa indices varied between 0.15 and 1.00, and agreement percentages from 52, to 100. Kappa index was poor (0.15) in evaluation of the bone structure. The mean DMFT index for the students was 8.4. A sound dentition was found in 6.6%, and 48.4% of the students were free of caries. The mean number of carious lesions was 1.1. There were 50 retained roots (49 from primary teeth). 76.6% of the students had one or more unerupted wisdom teeth and 22.7% had radiologic changes typical of pericoronitis in the region of the mandibular third molars. 16.2% of the students had at least one missing wisdom tooth. Bone structure was normal in 92.4% of the students, idiopathic osteosclerosis being the most common divergence (3.5%). Arthrotic changes in the condyles were found in 9% of the students. In eight cases there was erosion of the condyles, which was diagnosed as arthritis. Styloid ligament calcifications were found in 21.5% of the students. In the maxillary sinuses, male students exhibited changes 1.7 times more often than female students (26.3% in males and 15.1% in females). PMID- 8432104 TI - Dental health habits of 3-year-old Finnish children. AB - The aim was to study whether 3-yr-old children's toothbrushing habits are associated with the child's other dental health habits and whether the mother's background influences the child's toothbrushing frequency. The survey used stratified randomized cluster sampling, confidential questionnaires and clinical dental examinations. A random sample of 1443 (91.2%) of a Finnish province's 1582 primiparous women participated in the study at the onset of their pregnancy. Dental health care clinics of the public health care system carried out dental examinations in 1018 (83.5%) 3-yr-old children born of these pregnancies. The variables used in the study included consumption of juice at night and sugar at the age of 1.5 yr and the use of fluoride tablets and sweets at the age of 3. The mother's background factors included age, basic education and occupation. Daily toothbrushing was practised by 78.2% of the children. Addition of sugar to the diet and frequent use of sweets at the age 3 were more common in those who brushed their teeth only occasionally, whereas the use of fluoride tablets was less frequent in them than in those brushing their teeth every day. Of the mothers' background factors, age was the most significant. The youngest mothers paid the least attention to their children's toothbrushing habits. The proportion of those brushing their teeth was 67.9% in rural areas, 78.6% in semi-urban population centers and 80.1% in towns (P = 0.02). The results indicate that the health education provided by dental health care clinics should be focussed on young mothers and rural families.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8432105 TI - Number of amalgam fillings in relation to cardiovascular disease, diabetes, cancer and early death in Swedish women. AB - Altogether 1462 women aged 38, 46, 50, 54 and 60 yr were initially examined in 1968-69 in a combined medical and dental population study in Gothenburg, Sweden. Number of tooth surfaces restored with amalgam fillings was assessed. The incidences of myocardial infarction, stroke, diabetes, cancer and overall mortality were determined during a 20-yr follow-up period. Women with few amalgam tooth fillings had increased incidence of myocardial infarction, stroke, diabetes and early death compared with women with a large number of fillings. However, the significant inverse correlations between number of amalgam tooth fillings and the endpoints studied disappeared when number of teeth and socioeconomic group were included in a multivariate analysis. The study thus did not provide any evidence for a correlation between amalgam fillings and cardiovascular disease, diabetes, cancer or early death. PMID- 8432106 TI - Long-term evaluation and rerestoration of amalgam restorations. AB - In this study, 1544 class-II amalgam restorations were made and evaluated for 10 yr and the reasons for rerestoration were registered. Two categories of failure could be established: failures due to poor restorative technique (true failures) and those not due to poor restorative technique (false failures). After 10 yr, 1415 restorations were evaluated. Only 120 restorations (8.5%) had been replaced, most of these replacements being true failures (105 = 87.5%), which could be divided into: isthmus fracture (37), fracture of the enamel cusp (25), recurrent caries (16), partial fracture of the restoration (9), severe marginal breakdown (5), pulpal pathology (7) and others (6). The false failures (15) could only be classified into: caries elsewhere in the tooth (15). Origins of the true failures were the operator, the material (amalgam) and the type and size of the restoration. In this study, there were significantly more replacements of larger restorations than of smaller ones and more replacements in molars than in premolars. There is also a significant difference among the replacements by the various operators but not between the various types of amalgam. Origins of the false failures seem to be more related to patient factors like caries activity, caries susceptibility and oral hygiene, but chewing habits (bruxism) may also play a role. PMID- 8432107 TI - Oral health problems and needs of nursing home residents. AB - The problem of dental neglect and high levels of unmet dental needs among elderly residents of long term care facilities has been widely documented in literature. A survey was conducted of 1063 residents in 31 nursing homes throughout Washington (representing 11% of all facilities in the state). The greatest single need among dentate elderly was for routine oral hygiene (72%), while for denture wearers adjustment of loose dentures was the primary need (46.4%). Periodontal problems were slightly more prevalent than root caries (43% and 36% respectively) among dentate elderly. Dry mouth was found in 10% of residents. Oral conditions were worse in larger facilities located in rural and moderate size communities, and those under a proprietary corporation. These results suggest that daily oral hygiene and regular check-ups by a dental professional are most needed by frail elderly, especially in large, proprietary homes in rural and moderate size communities. Education of nursing home staff and the elderly themselves in the importance and methods of home care are also critical needs. PMID- 8432108 TI - Oral health status of a group of elderly Canadian Inuit (Eskimo). AB - Fifty-four Inuit elders, representing 90% of the individuals 60 yr of age and older in three communities in the Keewatin region of the Canadian Northwest Territories, were examined for dental caries, periodontal disease, levels of edentulism, and the fit and quality of denture prostheses. These elders had a mean of 2.8 +/- 3.5 decayed teeth and a DMFT of 26 +/- 13 which reflected significant tooth loss. The Root Caries Index for subjects with gingival recession was 19%. Periodontal pocket assessments revealed that 86% of the individuals examined had CPITN readings of either 3 or 4. Over one third of the elders were totally edentulous, most of them female. Only 47% of these individuals wore complete dentures. Denture fit assessment revealed that 36% of the complete maxillary dentures and 42% of the complete mandibular dentures fit poorly. The overall oral health findings for these Inuit elders differed from those found in other older populations; however, the present findings may be the norm for a population undergoing a cultural transition. PMID- 8432109 TI - The clinician's ability to identify caries risk subjects without saliva tests--a pilot study. AB - The average clinician's ability to identify caries risk children without any saliva tests was studied in field conditions. The results suggest that a clinician can reach a high level in prediction of future caries occurrence through the use of clinical and sociodemographic information routinely available at annual clinical examinations. PMID- 8432110 TI - CT diagnosis of emphysema. It may be accurate, but is it relevant? PMID- 8432111 TI - Environmental tobacco smoke and asthma. PMID- 8432112 TI - Mitral stenosis and left atrial thrombus. Role of transesophageal echocardiography. PMID- 8432113 TI - A catastrophe is brewing. PMID- 8432114 TI - Gene analysis of pulmonary pseudolymphoma. AB - The value of gene analysis was assessed in patients with pulmonary pseudolymphoma. Two patients with histopathologic evidence of pseudolymphoma took part in the study. High molecular weight DNA was extracted from resected specimens and digested with restriction enzymes, followed by southern blotting. Gene rearrangement of immunoglobulins and T-cell receptors was investigated using DNA probes against heavy chain (H chain), kappa chain, and lambda chain of immunoglobulin genes and that against the beta-chain of T-cell receptor genes. Both patients with pseudolymphoma showed rearranged bands for the H chain; B-cell lymphoma was diagnosed from the gene analysis. Gene analysis is a valuable method when it is difficult to judge whether the tumor cells are of T-cell origin or B cell origin in phenotype analysis by immunohistologic studies and when it should be judged whether or not the lymphoid hyperplasia is tumor related. PMID- 8432115 TI - Room-temperature thermodilution cardiac output. Central venous vs side port. AB - OBJECTIVE: To assess the accuracy of room-temperature thermodilution cardiac output measurements from the side port (SP) of the introducer catheter through which the pulmonary artery flotation catheter is inserted. DESIGN: Central venous port (CVP) cardiac output measurements were compared with SP cardiac output measurements using the same right-heart catheter. SETTING: The general intensive care unit of the Hospital for Joint Diseases, Orthopedic Institute, New York. PATIENTS: Thirty one orthopedic patients with 31 different right-heart catheters placed in the right internal jugular or right subclavian position were evaluated. INTERVENTION: Four injections of 10 ml of normal saline solution at room temperature were made through each port; the results of the last three injections were averaged. Cardiac output determinations from both ports were completed in less than 10 min. The order of port injection was random. RESULTS: A significant difference was noted between cardiac output determinations from the two ports (p < 0.001, paired Student's t test) with the SP slightly overestimating thermodilution cardiac outputs by 6.34 +/- 8.38 percent compared to the CVP. A significant correlation was noted between both ports (r = 0.97, p < 0.001) with the linear regression line starting at the origin (y intercept not significantly different from zero) with a slope (1.07) significantly greater than 1. CONCLUSION: If the proximal CVP becomes nonfunctional, room-temperature thermodilution cardiac outputs from the SP can be used with the understanding that a slight overestimation of cardiac output will occur. PMID- 8432116 TI - Pneumothorax. Results of thoracoscopy and pleurodesis with talc poudrage and thoracotomy. AB - A retrospective study was performed of the evaluable data in 710 patients with a spontaneous pneumothorax. The male:female ratio was 3.4:1. A thoracoscopy was performed in 622 patients. The two main therapeutic strategies were pleurodesis with talc poudrage (n = 356) and thoracotomy (n = 248). The success rate of talc poudrage was 88 percent, and in the group failures who have undergone surgery afterwards, we found unexpected bullous structures in 20 of 37 patients. The success rate of operation (bullectomy, pleurectomy, or resection) was 97 percent. Our conclusion is that aggressive therapy in spontaneous pneumothorax is acceptable, with a high success rate with very few complications. The diagnostic thoracoscopic evaluation needs to be in experienced hands, especially to inspect the apical lobes with the Valsalva maneuver. PMID- 8432117 TI - Left atrial thrombus and spontaneous echo-contrast in nonanticoagulated mitral stenosis. A transesophageal echocardiographic study. AB - OBJECTIVE: The aim of the study was to investigate if evidence at transthoracic echocardiography (TTE) of left atrial (LA) thrombus and LA spontaneous echo contrast (LA SEC), which are potential precursors of embolization, can be predicted by clinical and TTE variables in nonanticoagulated mitral valve stenosis (MS). DESIGN: Clinical (age, NYHA class, rhythm, previous embolization) and TTE variables were related to transesophageal echocardiography (TEE) evidence of LA thrombus and/or LA SEC. SETTING: Nonanticoagulated MS was the setting. PATIENTS: Fifty-nine patients had MS, and they were not receiving anticoagulant or antiplatelet therapy (24 in sinus rhythm and 35 in atrial fibrillation). Previous arterial embolization had occurred in 12 patients (20.3 percent). MEASUREMENTS: The following TTE variables were analyzed: mitral orifice area (pressure half-time method), mitral gradient (Bernouilli's equation), LA end systolic area, and mitral regurgitation (color Doppler grading). LA thrombus and LA SEC were analyzed by monoplane TEE. RESULTS: LA thrombus was found by TEE in 12 patients (20.3 percent). Of these 12, 11 (91.6 percent) were in atrial fibrillation. LA SEC was found by TTE in 2 patients (3.5 percent) and by TEE in 40 (67.8 percent) (p < 0.001). Previous embolization had occurred only in patients with LA SEC, of whom 5 had and 7 did not have LA thrombus. Patients with LA SEC, compared with those without LA SEC, were characterized by more frequent advanced NYHA class, atrial fibrillation, smaller mitral valve area, and larger LA size. By multivariate regression analysis, atrial fibrillation and LA end systolic area were factors related to both LA thrombus and LA SEC, whereas mitral area was related only to LA SEC. However, whereas LA SEC was accurately predicted by the presence of atrial fibrillation (sensitivity: 87.5 percent; specificity: 100 percent) and a LA area > or = 30 cm2 (sensitivity: 72.5 percent; specificity: 89.5 percent), among patients with LA SEC no clinical or TTE variable accurately identified those with actual LA thrombus. CONCLUSIONS: TEE is not necessary in many patients with MS in order to recognize LA SEC. However, when actual LA thrombus detection is necessary for clinical decision making, TEE should be performed. PMID- 8432118 TI - Effects of a bronchoprovocation challenge test with cigarette sidestream smoke on sensitive and healthy adults. AB - In order to study the acute effects of environmental tobacco smoke on lung function, a cigarette sidestream smoke provocation test (analogous to a nonspecific bronchial provocation test) was performed. Ten persons with airways hyperreactive to methacholine and ten normoreactive persons were tested. A dose response relationship was found for symptoms. The lung function of the normoreactive persons was not altered by short-time inhalation of sidestream smoke. The hyperreactive subjects, however, experienced significant decreases in FEV1, FVC, and MEF50. The decrease was most pronounced after the lowest dose of 2 ppm smoke-induced CO, leading to a mean fall of 6.3 percent in FEV1. Five of ten subjects with hyperreactive airways showed a decrease in FEV1 of more than 10 percent during the sidestream smoke provocation, one of them a decrease of over 20 percent after inhalation of 16 ppm CO sidestream smoke. We conclude that even short exposure to low concentrations of cigarette sidestream smoke causes significant impairment of lung function in sensitive persons. PMID- 8432119 TI - Repeated tuberculin testing in patients with active pulmonary tuberculosis. AB - OBJECTIVE: The proportion of tuberculin reactors in a population and the intensity of tuberculin reactions have been shown to increase with increasing exposure to mycobacterial infection, eg, repeated BCG immunization. These observations suggested that tuberculin reactivity would become uniformly high in individuals with a high mycobacterial load who did not have a known cause of anergy. Since tuberculin reactivity has been measured to evaluate the possible genetic regulation of responses to mycobacteria in humans, it is important to study its behavior under conditions of ongoing, maximal exposure to mycobacteria. In the present study, we determined the mean size of tuberculin reactivity in BCG immunized and unimmunized patients with pulmonary tuberculosis of recent onset, and the stability of tuberculin reactions during and after treatment of pulmonary tuberculosis. METHOD: Serial tuberculin testing was performed on patients with newly diagnosed active pulmonary tuberculosis diagnosed over a period of 2 years at the National Institute for Respiratory Diseases in Santiago, Chile. The first tuberculin test was performed at the time of diagnosis in 58 patients. Repeated tuberculin testing was performed 2 weeks later in 15 patients with initial reaction sizes < 15 mm. Four additional tuberculin tests were performed, one each at 3-months intervals in 42 patients regardless of the size of the initial tuberculin reaction. RESULTS: Tuberculin reactions at entry had a unimodal distribution in patients both with and without BCG scars (14.8 +/- 5.0 mm and 16.5 +/- 5.2 mm, respectively). A second tuberculin test in patients with initial reaction sizes < 15 mm showed a moderate, statistically significant increase in the mean reaction size (PPD1: 10.1 +/- 3.2 mm; PPD2: 11.9 +/- 4.8 mm). Repeated tuberculin testing over 1 year revealed no significant changes in reaction size. The mean reaction sizes were 15.8 +/- 5.0 mm at entry, 15.5 +/- 5.4 mm at 3 months, 17.2 +/- 5.2 mm at 6 months, 17.0 +/- 5.1 mm at 9 months, and 16.7 +/- 54 mm at 12 months. The standard deviation of a random observation within patients was 5.3 mm. The largest variations due to increased reactivity after 6 months of treatment were observed in patients with reaction < 15 mm at entry compared with hyperergic patients, and in BCG-immunized patients compared to unimmunized patients. CONCLUSIONS: In the presence of an ongoing mycobacterial infection, patients without anergizing conditions express a tuberculin reactivity that is relatively constant during and after treatment of pulmonary tuberculosis. The size and stability of the reactions seem to be determined by individual conditions that include the tuberculin reactivity at the time of diagnosis and the BCG immunization status. PMID- 8432120 TI - A rapid tuberculosis screening program for new mothers who have had no prenatal care. AB - We developed a Rapid Tuberculosis Screening Program for use in women who have not had prenatal care. All patients who presented for delivery without a documented tuberculin skin test (TBN-ST) were given a symptom questionnaire. Those who had a positive response to any of the questions received a chest roentgenogram to rule out active disease. All patients with a negative questionnaire had a TBN-ST soon after admission. The test was read at the time of discharge, whether or not 48 h had elapsed, and individuals who had 5 mm or more of induration at before 48 h and 10 mm or more induration at 48 to 72 h were considered reactors. Of 1,412 patients who received a TBN-ST, 259 were reactors. One case of active disease was diagnosed. Approximately 75 percent of "true" tuberculin reactors will be detected by this method. We suggest that by using the TBN-ST concurrently with a questionnaire, most patients infected with Mycobacterium tuberculosis can be identified. PMID- 8432121 TI - Bronchial hypersensitivity in asthmatics in long-term symptom-free state. AB - Improvement of asthmatic symptoms was shown to be closely associated with a decrease in bronchial hypersensitivity to histamine inhalation. Thus, the patients' clinical backgrounds were compared between 26 long-term cases whose symptom-free state lasted more than 1 year and 15 short-term cases whose symptom free state ceased within 1 year. Among backgrounds, only the intrinsic type of asthma was significantly higher in number in the long-term group than in short term group (65 percent vs 27 percent). The histamine threshold after the patients became symptom-free was significantly higher in the long-term group. In the short term group, the values of PC20 just before the termination of the symptom-free state were all less than 5,000 mg/L of histamine. However, in the long-term group, the values of the PC20 for the final test were mostly over 5,000 mg/L. Decrease in bronchial hypersensitivity is considered to be a very important aim of therapy in bronchial asthma. PMID- 8432122 TI - Risk factors for ventilatory impairment among middle-aged and elderly men. The Normative Aging Study. AB - To evaluate the relationship of atopy and inflammation to the occurrence of ventilatory impairment, we studied 1,301 middle-aged and older men participating in the Normative Aging Study at the time of their 1984 to 1987 examination. Screening at entry to the study in the 1960s had excluded subjects with asthma and other chronic diseases at that time. After adjustment for smoking status and pack-years in this cross-sectional analysis, a weak inverse relationship between FEV1 and blood eosinophil count was not statistically significant, and FEV1 showed no relationship to blood eosinophil count as a percentage of total leukocytes. A weak inverse relationship between FEV1 and serum total IgE concentration was not statistically significant. Cutaneous immediate hypersensitivity to one or more common aeroallergens was not related to FEV1. A significant inverse relationship between FEV1 and blood total leukocyte count was observed in never and former smokers. FEV1 was significantly lower in subjects reporting usual phlegm production. These findings suggest that ventilatory impairment is not related to atopic status among middle-aged and older men without a history of asthma. The inverse relationship between total leukocyte count and FEV1 in this sample supports the hypothesis that nonallergic inflammation plays a role in the pathogenesis of chronic airflow obstruction in this group. PMID- 8432123 TI - Prospective evaluation of the incidence of bacteremia after protected specimen brushing in ICU patients with and without pneumonia. AB - To test the hypothesis that the use of protected specimen brushing (PSB) via flexible bronchoscopy does not predispose to bacteremia in ICU patients, we prospectively performed aerobic and anaerobic blood cultures immediately following bronchoscopy with PSB. A total of 123 episodes in 68 consecutive patients with suspected pneumonia were analyzed. Blood cultures were negative in 110 cases (89 percent) and positive in 13 cases (11 percent) (p < 0.001). Twelve of these 13 patients with positive blood cultures had quantitative PSB specimen cultures showing nonsignificant growth (< 10(3) CFU/ml). In nine patients, the bacteria recovered from blood cultures (coagulase-negative staphylococci or sarcina) were considered nonpathogenic according to conventional criteria. Blood cultures grew a Staphylococcus aureus in two patients with previously documented staphylococcal septicemia. In one patient with no identifiable site of infection, the blood culture yielded Enterococcus faecalis. The only patient with both a positive blood culture and PSB culture results indicating pneumonia had different organisms recovered from the two samples. Blood cultures taken after PSB in the 17 other episodes of pneumonia (PSB specimen cultures > or = 10(3) CFU/ml) were negative. At the time of brushing and blood sampling for culture, none of these patients was receiving antibiotics active on the organisms found. In conclusion, the incidence of bacteremia after PSB in ICU patients seems very low even in patients with documented pneumonia. Substantial savings would result from not performing routine blood cultures after PSB. PMID- 8432124 TI - Comparative efficacy of bronchoalveolar lavage and telescoping plugged catheter in the diagnosis of pneumonia in mechanically ventilated patients. AB - The relative efficacy of telescoping plugged catheter (TPC) and bronchoalveolar lavage (BAL) in the diagnosis of pneumonia in mechanically ventilated patients has been compared in 45 subjects suspected of having pneumonia because of the presence of clinical and radiographic criteria. Diagnosis of pneumonia was strongly suggested in 25 of the 45 patients, and definitely confirmed in 10 of them. The diagnostic threshold to assess a quantitative bacterial culture as positive was a growth on BAL of > or = 10(5) cfu/ml and on TPC of > or = 10(3) cfu/ml. The BAL specimen cultures established the diagnosis in 19 cases (76 percent). In the remaining six patients, this technique did not permit the assessment of the diagnosis, which was established by other procedures (TPC, blood cultures, clinical outcome, or autopsy). False-positive results were not found. Sensitivity and specificity for BAL cultures were 76 percent and 100 percent, respectively. Telescoping plugged catheter established the presence of pneumonia in 16 patients (64 percent). Combining both techniques, the sensitivity increased up to 88 percent, maintaining specificity of 100 percent. In summary, BAL has a greater sensitivity than TPC in the diagnosis of pneumonias in mechanically ventilated patients. However, they are procedures that can complement each other. PMID- 8432125 TI - Early and late exercise testing. Usefulness after percutaneous transluminal coronary angioplasty. AB - Seventy-five patients 36 to 68 years of age were studied after undergoing successful single-vessel percutaneous transluminal coronary angioplasty (PTCA). In all cases exercise tests (ETs) were made prior to the procedure and 2 to 4 days and 6 months thereafter. Angiographic controls were performed on patients with positive ET. Both early and late ET carried out after dilatation lasted significantly longer. Patients were able to tolerate greater work loads and their heart rates and arterial blood pressures also were higher. The ETs conducted prior to PTCA were positive in 62 patients. After dilatation, the early test was positive in 18 and the late test, in 10. Angiographic controls revealed restenosis in 75 percent of patients with single-vessel disease and positive ET. Thus, the results of ETs in patients with single-vessel disease tend to become negative after successful PTCA. Early and late positive ETs are associated with restenosis, while negative ETs indicate a good prognosis. PMID- 8432126 TI - Control of ventilation, respiratory muscle strength, and granulomatous involvement of skeletal muscle in patients with sarcoidosis. AB - Granulomatous involvement of skeletal muscle occurs in 50 to 80 percent of patients with sarcoidosis. How this may affect respiratory muscle function in sarcoidosis is not known. To attempt to answer this question, we compared respiratory function and muscle force generation, and control of ventilation in 12 untreated patients with 12 healthy, nonsmoking subjects. While seated, room air breathing, measurements included expiratory reserve volume (ERV), components of breathing pattern, and occlusion pressure at 1 s (P0.1). Three of nine patients who consented to muscle biopsy demonstrated granulomatous involvement on histologic examination, and Pmax values less than the group mean; however, some patients without muscle granulomas also demonstrated low Pmax values. Breathing pattern in the sarcoid patients was rapid and shallow, but not related to the degree of radiographic infiltration or respiratory elastance. Mean inspiratory flow (VT/TI), minute ventilation, and P0.1 were, in general, greater than in the control subjects, indicating an increase in central drive. There was a significant inverse correlation between FVC and P0.1, and a weak inverse relationship between ERV and P0.1. With no significant difference between group "effective impedances" (P0.1/(VT/TI)), findings indicate that in the sarcoidosis group, decreased muscle force generation was compensated for by an increase in central drive. Granulomatous infiltration may be one of many factors contributing to respiratory muscle weakness in sarcoidosis. PMID- 8432127 TI - Specificity and sensitivity of distinctive chest radiographic and/or 67Ga images in the noninvasive diagnosis of sarcoidosis. AB - An analysis of gallium-67 (67Ga) uptake in the lacrimal and salivary glands and intrathoracic lymph nodes was made in 162 patients with sarcoidosis, consisting of a large number with chronic "fibrotic" disease, and 167 HIV-positive patients (most of whom have/had AIDS). This study was designed to further assess the diagnostic sensitivity and to fully evaluate the diagnostic specificity of chest radiographic and/or 67Ga uptake findings found to be characteristic of sarcoidosis. A lambda 67Ga uptake image or a panda 67Ga uptake image with associated bilateral, symmetrical hilar lymphadenopathy (BSHL) or bilateral, symmetrical parenchymal infiltration indicative of pulmonary fibrosis on chest radiograph (BSIF) was commonly present in sarcoidosis. These distinctive 67Ga uptake images were frequently observed in patients with normal chest radiographs (stage 0 [33 percent]), as well as in patients with BSHL on chest radiograph whether the disease was in an "early" stage, ie, stages I (74 percent) and II (90 percent) or a chronic "fibrotic" stage, ie, IVa (71 percent). A panda 67Ga uptake image was observed in 8 percent of HIV-positive patients; however, a lambda 67Ga uptake image alone or any of the other chest radiographic and/or 67Ga uptake patterns distinctive for sarcoidosis were not observed in any of 167 HIV-positive patients. We conclude that (1) a lambda 67Ga thoracic image (usually associated with a panda 67Ga uptake image) or a panda 67Ga uptake image together with BSHL or BSIF on chest radiograph represent distinctive patterns that are highly specific and sensitive for the noninvasive diagnosis of the majority of sarcoidosis patients, and (2) the finding of a panda 67Ga uptake image, not associated with BSHL or BSIF on chest radiograph, should suggest, in addition to a limited number of readily diagnosable disorders, the presence of a positive HIV status. PMID- 8432128 TI - Lung cancer in patients with immunodeficiency syndrome. AB - We report adenocarcinoma of the lung in seven patients with human immunodeficiency virus (HIV) infection. We compared age, clinical findings and survival data with a sex-matched control group of HIV-negative patients with adenocarcinoma of the lung. Median age of HIV-infected patients with lung cancer was lower than in control patients with lung cancer. The HIV-infected patients had more systemic symptoms and abnormal physical findings than control subjects. Both groups had smoking histories. Laboratory data were similar but control subjects had lower blood oxygen tensions than did HIV patients; HIV patients had more abnormalities on chest roentgenograms and computed tomography scans than did control subjects. All HIV-infected patients were stage IV. Median survival was 4 weeks. For control patients, 50 percent had stage IV disease; median survival was 25.5 weeks. Thus, patients with HIV infection develop lung cancer at a younger age than sex-matched control subjects and undergo a more fulminant course with shortened survivals. PMID- 8432129 TI - Lack of efficacy of intrapleural bupivacaine for postoperative analgesia following thoracotomy. AB - Intrapleural bupivacaine has been reported to be effective for analgesia following cholecystectomy and thoracic surgery. Twenty patients who had a posterolateral thoracotomy were studied in a randomized, double-blind, placebo controlled fashion. Patients were assigned to receive intrapleural administration of either 0.5 percent bupivacaine or saline solution every 4 h for 12 doses postoperatively, as well as narcotic analgesics as needed for additional pain control. Pain was assessed using a visual analogue scale. Narcotic analgesic use, duration of hospitalization, and the development of complications were recorded. There were nine evaluable patients who received bupivacaine, and ten patients who received placebo. The age, sex, and type of operation were similar in the two groups, and the procedures were performed by the same two surgeons. The mean pain score at 24 h postoperatively was 5.8 +/- 0.8 in the bupivacaine group and 6.0 +/ 0.6 in the placebo group. At 48 h, the scores were 4.6 +/- 0.8 in the bupivacaine group and 5.1 +/- 0.9 in the placebo group. The mean dose of morphine sulfate or equianalgesic dose of meperidine during the first 24 h was 13.9 +/- 3.7 mg in the bupivacaine group and 12.6 +/- 1.8 mg in the placebo group, and during the next 24 h it was 40.0 +/- 13.4 mg in the bupivacaine group and 38.0 +/ 9.2 mg in the placebo group. The mean duration of hospitalization was 12.8 +/- 3.2 days in the bupivacaine group and 12.1 +/- 2.9 days in the placebo group. Two patients who received bupivacaine and three patients who received placebo had development of pneumonia or atelectasis postoperatively. There was no statistically significant difference in any parameter between those who received bupivacaine and those who received placebo. Thus, there was no subjective or objective clinical benefit of this method of postoperative analgesia compared with placebo following posterolateral thoracotomy. PMID- 8432130 TI - Etiologic factors of chronic bronchitis in dairy farmers. Case control study in the Doubs region of France. AB - Relationships were investigated between chronic bronchitis and plant dust exposure assessed by quantification of barn threshing and cattle foddering and chronic bronchitis and acute respiratory syndromes after plant mold dust exposure. Two groups of male dairy farmers were studied in the Doubs region, France: 197 with chronic bronchitis and 163 control subjects without chronic bronchitis. There was no relationship between chronic bronchitis and exposure. Thirty-three chronic bronchitis patients had semidelayed respiratory syndromes (SDRS) vs two control subjects. Twenty-seven times out of 33 (16 of 17 in the nonsmokers), the SDRS preceded chronic bronchitis. Past history of acute respiratory syndromes during barn threshing (RSBT) was more frequent in chronic bronchitis; RSBT always preceded chronic bronchitis. It is concluded that host factors are important in chronic bronchitis and that acute effects after exposure may be predisposing factors to chronic bronchitis. PMID- 8432131 TI - Hypoxemia during altitude exposure. A meta-analysis of chronic obstructive pulmonary disease. AB - A previous study identified spirometric testing as a useful adjunct for estimating PaO2 during altitude exposure in patients with chronic obstructive pulmonary disease (COPD). We sought to examine the validity of this finding by quantitative analysis of recent published reports. We analyzed acute hypoxic exposures from five prior studies involving 71 patients. Across all studies, the change in arterial oxygen tension per unit change in inspired oxygen partial pressure (linear slope, dPaO2/dP1O2) correlated with the preexposure forced expiratory volume in 1 s (FEV1, p < 0.01). The correlation with FEV1 held for values weighted or unweighted by sample size, with rotating deletion of each study from analysis one at a time, and with semilog slope as the dependent variable. A formula derived from the semilog slope relationship with FEV1 gave accurate description of the mean hypoxic response in each prior study and individual responses from one study (n = 18): ln (PaO2alt/PaO2g) = Kn.(PIO2alt PIO2g). We found that FEV1 modulated the values of kn in this study. We conclude, based on analysis of prior studies, that preexposure arterial oxygen tension and FEV1 both influence the prediction of PaO2 during hypoxic exposures in patients with COPD. PMID- 8432132 TI - Increased Pneumocystis carinii recovery from the upper lobes in Pneumocystis pneumonia. The effect of aerosol pentamidine prophylaxis. AB - STUDY OBJECTIVE: To determine the relative distribution of Pneumocystis carinii in the lungs of patients with P carinii pneumonia and to see the effect of aerosol pentamidine prophylaxis on this distribution. DESIGN: A prospective study of all human immunodeficiency virus-infected patients with pulmonary symptoms over a nine-month period. Patients were followed up for at least six weeks after bronchoscopy. SETTING: Inpatient and outpatient service at one referral center. PATIENTS: Human immunodeficiency virus-infected patients with pulmonary symptoms were referred for evaluation. Those patients subsequently found to have P carinii pneumonia were studied. INTERVENTION: Bronchoalveolar lavage was performed in the middle lobe (or lingula) and the apical segment of the same lung. MEASUREMENTS AND RESULTS: The aspirated fluids were kept separate and modified Wright-Giemsa stained cytocentrifuge-prepared slides were made from each area, and the number of P carinii clusters per 500 nucleated cells was counted. Fifty patients were studied: 27 receiving pentamidine prophylaxis and 23 receiving no aerosol therapy. There was no significant difference in the amount of fluid retrieved by lavage from the middle or upper lobe for either group. Both groups had significantly lower numbers of P carinii clusters per 500 cells in the middle lobe (receiving pentamidine: 10 +/- 15.8 [SD]; not receiving pentamidine: 15 +/- 12.3) than in the upper lobe (receiving pentamidine: 22 +/- 19.8; not receiving pentamidine: 24 +/- 21.5; p < 0.02). In six patients, there were no P carinii organisms seen in the middle lobe lavage specimen. CONCLUSION: Pneumocystis carinii has a preference for the upper lobes which may be apparent even in patients not receiving aerosol pentamidine. In addition, yield for P carinii may be increased by performing lavage in the apical segment. PMID- 8432133 TI - Nonsmoking, non-alpha 1-antitrypsin deficiency-induced emphysema in nonsmokers with healed spontaneous pneumothorax, identified by computed tomography of the lungs. AB - This case-control study is based on an investigation of 27 nonsmoking patients with radiologically verified spontaneous pneumothorax (SP) and ten healthy never smoker control subjects. The posteroanterior and lateral radiographs of patients and control subjects were normal. They were all submitted to the same clinical, laboratory, and radiologic examinations, including computed tomography (CT) of the lungs, with the aim of detecting any parenchymatous lung changes. Emphysema like changes (ELCs) were detected on CT in 22 (81 percent) of the 27 patients, and if the ELC cases detected during interventional surgery are added, the frequency increases to 24/27 (89 percent). In 20 patients with unilateral SP, at least one ELC was found in 13 of the 20 SP-affected lungs, but only in five of the 20 lungs that were not diagnosed as having SP (p < 0.05). ELCs were found more frequently in the upper than in the lower lung regions (p < 0.05) and more frequently in the radiologically peripheral than in central regions (p < 0.001). No ELC was detected in the control group on CT. No alpha 1-antitrypsin deficiency was found in the 27 nonsmoking patients with radiologically verified SP who had ELCs despite the absence of these known promoters of emphysema. PMID- 8432134 TI - Graft position and pulmonary function after single lung transplantation for obstructive lung disease. AB - Single lung transplantation (SLT) has become a therapeutic option for the treatment of end-stage obstructive lung disease. Between January 1989 and June 1990, there were 14 patients with end-stage obstructive lung disease who underwent SLT. Eleven of these patients were surviving at 1 year following transplantation. Three of the patients had received left-sided SLT, and eight had received right-sided SLT. In the patients receiving left-sided SLT, the native right lung radiographically appeared to compress the left lung graft. In the patients receiving right-sided SLT, the native left lung did not appear to compress the right lung graft. We hypothesized that right SLT may provide a functional advantage over left SLT for patients with obstructive lung disease. We compared pulmonary function test results before and after transplantation (approximately 3 and 12 months) and compared quantitative ventilation-perfusion lung scan results between the patients with left SLT and those with right SLT. Additionally, we compared graded-exercise test results at 3 and 12 months after transplant between the two groups. Our data revealed no statistical difference in pulmonary function test results or graded-exercise test results between the two groups, although patients undergoing right SLT showed greater increases in FEV1 and forced vital capacity than those undergoing left SLT. Quantitative ventilation and perfusion were greater to the graft in patients receiving right sided SLT than in patients receiving left-sided SLT, most likely due to the larger size of the right lung. We conclude that there is no functional difference between patients undergoing left or right SLT for end-stage obstructive lung disease. PMID- 8432135 TI - Serum neopterin after lung transplantation. AB - OBJECTIVE: Neopterin (N), a marker for activated cell-mediated immunity, was assayed in the sera of 44 lung recipients early and late after transplantation. The study was a prospective, blind clinical trial designed to evaluate the following: (1) the daily dynamics of the serum neopterin/creatinine (N/C) ratio during the first 3 weeks after transplantation; (2) the correlation between changes in the serum N/C ratio and episodes of rejection or infection; (3) the correlation between the serum N/C ratio and the concentration of serum soluble interleukin 2 receptor (sIL-2R), a marker of T-cell activation; and (4) the potential value of monitoring the serum N/C ratio during noninvasive long-term follow-up of lung recipients. METHODS: Sera from lung recipients were collected every day or every 2 days for the first 3 weeks after transplantation (22 patients) and before fiberoptic bronchoscopy and routine consultation (44 patients). The N concentrations were determined by radioimmunoassay and sIL-2R levels were measured using a sandwich enzyme immunoassay. RESULTS: Serum N/C is an early and sensitive marker of immune activation in the 21 days following transplantation. The N/C ratios during early rejections (815 +/- 182 mumol/mol) and infections (677 +/- 75 mumol/mol) were higher than those in patients with no complications (160 +/- 32 mumol/mol). In contrast, the N/C ratio did not increase during rejection later after transplantation. More than 3 weeks after transplantation, an increase in the N/C ratio was specifically correlated with infections, mainly those due to cytomegalovirus (CMV) (control subjects, 132 +/- 12 mumol/mol; rejections, 163 +/- 25 mumol/mol; CMV pneumonia, 786 +/- 103 mumol/mol, p < 0.001). The N/C ratio correlated with sIL-2R serum levels (r = 0.625, p < 0.001). CONCLUSIONS: Our results indicate that more than 3 weeks after transplantation, the serum N/C ratio increases only in cases of infection, mostly CMV pneumonia. In contrast, both rejection and infectious complications are associated with an increased N production in the early postoperative period. PMID- 8432136 TI - Knowledge and attitude of healthy high school students toward bronchial asthma and asthmatic pupils. AB - One hundred sixteen healthy high school pupils were interviewed and completed a questionnaire concerning their knowledge about asthma and their attitude towards asthmatic peers. They were compared with 35 asthmatic pupils studying at the same school. The level of knowledge was quite satisfactory, with the knowledge of the asthmatic pupils being somewhat higher than that of the healthy pupils, but without statistical significance. There was a correlation with the age of the pupils in both groups (p < 0.0001). The source of pupils' knowledge came principally from the media (television and newspapers), the family (talking with parents), treating physicians, and school nurses. The healthy pupils displayed less tolerance toward the asthmatic disease and its limitations on activity than that displayed by the asthmatic pupils (p < 0.001). A correlation was found between the level of knowledge and attitude, with an increased level of knowledge implying a more tolerant attitude. A correlation was also found between tolerant attitudes and increasing age, increasing parental education, and the pupils' behavior marks. The recommendation of the survey is to improve the instruction regarding bronchial asthmatic diseases with classes taught by physicians or nurses. By increasing the knowledge of the healthy pupils at school, their attitudes will be more tolerant and positive toward the asthmatic pupils. PMID- 8432137 TI - Diagnosis of tuberculous pleurisy using the biologic parameters adenosine deaminase, lysozyme, and interferon gamma. AB - We compared the parameters pleural adenosine deaminase (PADA, determined in 405 patients), the PADA/serum ADA ratio (P/SADA; 276 cases), pleural lysozyme (PLYS, 276 cases), the PLYS/serum LYS ratio (P/SLYS; 276 cases), and pleural interferon gamma (IFN, 145 cases) regarding their ability to differentiate tuberculous pleural effusions from others. The 405 pleural effusions were classified by previously established criteria as tuberculous (91), neoplastic (110), parapneumonic (58), empyemas (10), transudates (88), or miscellaneous (48). The intermean differences between the tuberculous group and each of the others were statistically significant for all five parameters (p < 0.01 for PLYS and P/SLYS with respect to the empyema group; p < 0.001 otherwise), except for PADA and P/SADA with respect to the empyema group. All the tuberculous pleurisy cases had PADA values of 47 U/L or more, as compared to only 5 percent of the other cases (sensitivity, 100 percent; specificity, 95 percent). P/SADA was above 1.5 in 85.7 percent of tuberculous effusions and 11 percent of the others (sensitivity, 85.7 percent; specificity, 89 percent). PLYS, with a diagnostic threshold of 15 g/ml, had a sensitivity of 85.7 percent and a specificity of 61.6 percent; P/SLYS, with a threshold of 1.1, had a sensitivity of 67.3 percent and a specificity of 90.3 percent; and IFN, with a threshold of 140 pg/ml, had a sensitivity of 94.2 percent and a specificity of 91.8 percent. The lowest misclassification rate was achieved by PADA, with statistically significant differences (p < 0.001) with respect to P/SADA, PLYS, and P/SLYS, but not with respect to IFN. The only significant pairwise correlations among these parameters were between P/SLYS and PADA and between P/SLYS and P/SADA. We conclude that PADA and IFN are useful parameters for early diagnosis of tuberculous pleurisy, and that the other parameters considered have no advantages over PADA and IFN for this purpose (though the high specificity of P/SLYS may be noted). PMID- 8432138 TI - Cryosurgery in bronchoscopic treatment of tracheobronchial stenosis. Indications, limits, personal experience. AB - Cryosurgery is one of the techniques available for bronchoscopic treatment of malignant and nonmalignant tracheobronchial stenosis; other techniques are electrosurgery, laser therapy, and endobronchial brachytherapy. Our experience began in 1976 and includes more than 300 patients treated with bronchoscopic cryosurgery either for malignant (the majority) or for nonmalignant tracheobronchial lesions. This study was performed on 234 patients treated in the years 1979 to 1988 subdivided as follows: 183 malignant tumors, 44 benign tumors, and 7 tumors of uncertain prognosis (adeno). The study demonstrated satisfying results in both (palliative in the first case, almost radical in the second one). The aim of our work was to report our personal data and to compare advantages and limits of this technique to others. PMID- 8432139 TI - High concentrations of eosinophil cationic protein and eosinophil protein X in eosinophilic pleural effusions. AB - To analyze the association of the eosinophil granulocyte with pleural effusions, we measured the concentrations of two eosinophil proteins, eosinophil cationic protein (ECP) and eosinophil protein X (EPX), in pleural fluid and serum of 92 patients with pleural effusions of various causes. We observed significantly higher ECP and EPX concentrations in eosinophilic than in noneosinophilic pleural effusions (p < 0.001 and p < 0.05, respectively) and a positive correlation between the concentrations of both eosinophil proteins in pleural fluid and the total number of eosinophils in pleural fluid (ECP: r = 0.66, p < 0.0001; and EPX: r = 0.62, p < 0.0001). There was a positive correlation between the concentrations of ECP in pleural fluid and serum (r = 0.74, p < 0.0001) and between the concentrations of EPX in pleural fluid and serum (r = 0.41, p < 0.001). High ECP and EPX concentrations in pleural fluid indicated nonspecific etiology and not tuberculosis as the cause of the effusion. Our results suggest that eosinophils in pleural effusions release eosinophil proteins and probably actively participate in the local inflammatory reaction. PMID- 8432140 TI - Release of tumor necrosis factor-alpha from human alveolar macrophages is decreased in smokers. AB - It is known that smoking affects the development and maintenance of certain types of granulomatous lung diseases. To explore this mechanism(s), we measured tumor necrosis factor (TNF)-alpha concentrations in the culture supernatants of lipopolysaccharide (LPS)-stimulated alveolar macrophages (AMs) in 13 healthy nonsmokers, 13 healthy smokers, 13 nonsmoking sarcoid patients, and 16 smoking sarcoid patients. We found that the capacity of smokers' AMs to release TNF-alpha was significantly decreased both in the normal and sarcoid groups. We also confirmed the previous observation that there was an exaggerated TNF release in patients with pulmonary sarcoidosis. These results indicate a significant role of TNF-alpha in the pathogenetic mechanisms of pulmonary sarcoidosis and suggest the possible involvement of TNF in the mechanisms by which smoking modulates local immune phenomena. PMID- 8432141 TI - Effect of inhaled amiloride on the bronchial response to methacholine and cold air hyperventilation challenges. AB - Inhaled amiloride has been recently demonstrated to have an effect on the decline of pulmonary function in patients with cystic fibrosis. Other diuretics have been demonstrated to provide protection against bronchoconstriction in asthmatic subjects. We report on the effect of inhaled amiloride on cold air hyperventilation challenge (CAHC) and methacholine challenge in asthmatics. We studied nine subjects with mild-moderate asthma in a double-blind, placebo controlled, crossover study. Our results showed amiloride did not significantly protect against the bronchoconstriction induced by CAHC. Inhaled amiloride did not affect FEV1 in the hour after inhalation, and there was no significant difference between placebo or amiloride on the dose of methacholine causing a 20 percent fall in FEV1. Inhaled amiloride appears not to have a profile of action as previously seen with inhaled furosemide. PMID- 8432142 TI - The acute effect of ipratropium bromide bronchodilator therapy on cough clearance in COPD. AB - Using radiolabeled, monodispersed aerosols (99mTc-iron oxide) and gamma camera analysis, we measured the efficacy of cough for clearing mucus from the airways of the lung following inhalation of the bronchodilator ipratropium bromide (IB) (Atrovent, Boehringer Ingelheim, Inc), a drug that has been shown to have no effect on mucociliary clearance in COPD. Clearance of radiolabeled aerosol was studied over a 2.5-h period on three separate days, a control day with no coughing, and two study days during which the patient performed controlled cough maneuvers over the course of clearance measurements following IB or placebo therapy (double blind, crossover). Fifteen patients, age > 45 years, with stable moderate-to-severe airway obstruction (mean FEV1/FVC = 0.45) were studied. IB diminished the effectiveness of cough for clearing the radiolabeled particles from the airways. This effect of IB on cough clearance may be due to (1) changes in the airflow dynamics induced by bronchodilation or (2) altered rheology or depth of airway secretions. PMID- 8432143 TI - Surfactant protein-A concentration in bronchoalveolar lavage fluids of patients with pulmonary alveolar proteinosis. AB - Pulmonary alveolar proteinosis (PAP) is characterized by accumulation of large quantities of lipoproteinaceous materials in alveoli. Surfactant protein A (SP-A) is the predominant phospholipid-associated glycoprotein in pulmonary surfactant and is specific to the lung. The contents of SP-A in bronchoalveolar lavage (BAL) fluids of patients with PAP were measured with an enzyme-linked immunosorbent assay using two monoclonal antibodies to human SP-A to evaluate its usefulness for diagnosis. Concentration of SP-A in BAL fluid in PAP was significantly increased in comparison with that of normal volunteers. The ratio of SP-A to protein in BAL fluid of PAP was at almost the same level as in normal subjects, while the ratio of SP-A to phospholipid in PAP was significantly higher. These results indicate that measurement of BAL fluid SP-A is of clinical value for diagnosis of PAP and should be used as a biochemical diagnostic tool in the clinical laboratory. PMID- 8432145 TI - Pulmonary function at diagnosis of amyotrophic lateral sclerosis. Rate of deterioration. AB - The purpose of this study was to determine the degree of respiratory muscle impairment in patients with newly diagnosed amyotrophic lateral sclerosis (ALS) and the subsequent rate of decline of respiratory function. Thirty-one of 36 patients had respiratory muscle weakness at presentation, although only 7 complained of any respiratory symptoms. Vital capacity (percent predicted) was significantly lower in the symptomatic group (55.9 +/- 20.3) compared with the asymptomatic group (76.4 +/- 21.0). Respiratory muscle impairment as measured by vital capacity (percent predicted) was related to stage of disease at presentation. Rate of decline of respiratory muscle strength as measured by VC ( 3.5 percent/month), negative inspiratory pressure (NIF) (+2.9 cm H2O/month), and positive expiratory pressure (PEP) (-3.4 cm H2O/month) tended to be linear with a great deal of interpatient variability. It is concluded that early measurement of respiratory muscle strength in ALS with subsequent follow-up studies may be useful in determining overall prognosis and in decision making. PMID- 8432144 TI - Mechanisms of impaired arterial oxygenation in patients with liver cirrhosis and severe respiratory insufficiency. Effects of indomethacin. AB - The mechanisms of impaired arterial oxygenation that occur in certain patients with chronic liver cirrhosis are still debated. In the present study, we investigated nine cirrhotic patients with severe respiratory disability (mean PaO2, 64 +/- 5 mm Hg), using the inert gas elimination technique to assess the distribution of ventilation-perfusion (VA/Q) ratios. We also determined shunt fraction during pure oxygen breathing, both in supine and sitting positions. To test the hypothesis that vasodilating prostaglandins could contribute to alter gas exchange in such patients with cirrhosis, we examined the hemodynamic and gasometric responses to indomethacin, 50 mg IV, in six of them. During baseline conditions, patients had high cardiac index (CI, 4.9 +/- 0.2 L/min/m2), and low pulmonary (PVR, 1.78 +/- 0.37 mm Hg/L/min/m2) or systemic (SVR, 17.7 +/- 1.15 mm Hg/L/min/m2) vascular resistances. Large intrapulmonary shunt fraction was documented in each patient with a mean value of 19.6 +/- 2.7 percent. Small perfusion in low VA/Q areas was associated with shunt in only three patients (2.5 to 5.3 percent of blood flow). Arterial PO2 was negatively related to shunt (p < 0.01) and to the dispersion of blood flow distribution (p < 0.02). There was no difference between measured and predicted PaO2. Shunt estimates from the inert gas and the 100 percent O2 breathing techniques were, respectively, 19.6 +/- 2.7 percent and 21.7 +/- 3.0 percent. During 100 percent oxygen breathing, changing from supine to sitting position decreased PaO2 from 401 +/- 50 to 333 +/- 64 mm Hg (p < 0.02), while O2 shunt remained unchanged, arteriovenous difference widened, and mixed venous PO2 decreased, from 61 +/- 3 to 47 +/- 4 mm Hg (p < 0.001). Indomethacin did not improve gas exchange or VA/Q distribution and did not affect systemic or pulmonary hemodynamics. The results show that in cirrhotic patients with severe respiratory disability, intrapulmonary shunting is the main determinant of impaired gas exchange, with no evidence of a defect in oxygen diffusion or an extrapulmonary shunt. Vasodilating prostaglandins do not appear to contribute to these alterations. PMID- 8432146 TI - Overshoot in mixed venous oxygen saturation during recovery from supine bicycle exercise in patients with recent myocardial infarction. AB - During recovery from dynamic exercise, systemic oxygen extraction rapidly decreases below the resting level in patients with heart failure, which leads to a subsequent increase in mixed venous oxygen saturation (SvO2) above its resting value (postexercise SvO2 overshoot). To evaluate the pathophysiologic basis of this phenomenon, postexercise SvO2 overshoot was evaluated in relation to hemodynamic, metabolic, and neurohumoral responses during recovery from maximal supine bicycle exercise in 22 patients with recent myocardial infarction. Postexercise SvO2 overshoot closely correlated with increased systemic vascular resistance (r = 0.79, p < 0.001) and reduced cardiac output (r = -0.74, p < 0.001), suggesting that SvO2 overshoot is primarily due to increased peripheral arteriovenous shunting caused by an enhanced peripheral vasoconstriction in the setting of reduced cardiac output. Postexercise SvO2 overshoot and systemic vascular resistance were significantly higher and cardiac output was significantly lower in New York Heart Association functional class 3 and 4 (8 patients) compared with class 1 and 2 (14 patients), whereas systemic arterial blood pressure was maintained at normal levels in both groups. Thus, postexercise SvO2 overshoot and, hence, decreased systemic oxygen extraction during recovery represent a compensatory response of an enhanced peripheral vascular tone that maintains systemic arterial blood pressure in the setting of reduced cardiac output by linking central and peripheral blood flow. PMID- 8432147 TI - The effect of venous occlusion with tourniquets on peripheral blood pooling and ventricular function. AB - Rotating tourniquets were once part of the traditional treatment of acute pulmonary edema. Their effectiveness has been questioned and vasodilator therapy has replaced them, but early favorable results suggested that they may play a beneficial role. A radioisotope technique was used to evaluate blood volume increments in the leg after venous occlusion at 60 mm Hg in 26 patients with left ventricular dysfunction following myocardial infarction. Mean radionuclide counts (reflecting the blood volume distal to the occlusion) increased from the preocclusion value. Thus, satisfactory trapping of blood is achieved. However, mean left ventricular ejection fraction (EF) decreased slightly but significantly and this decrease in EF was observed in 18 of 26 patients. Left ventricular end diastolic and end-systolic volume equivalents tended to decrease slightly but not in all patients. Mean stroke volume and cardiac output equivalents were reduced by 14 percent while peripheral resistance increased significantly. The present study thus fails to support the hypothesis that preload reduction by tourniquets improves left ventricular function; the exact opposite effect may occur because of increased afterload. PMID- 8432148 TI - Interatrial right-to-left shunting developing after pulmonary resection in the absence of elevated right-sided heart pressures. Review of the literature. AB - Considering the literature, a symptomatic right-to-left (R-L) shunt through a persistent foramen ovale (PFO), developing after a pulmonary resection, can occur without elevated right-sided heart pressures, but its frequency seems to be very low. However, considering the high frequency of a PFO in the normal population (20 percent) and the high frequency of pulmonary resections carried out today, it might be possible that this kind of complication is occurring more frequently, possibly in a more "benign" form, in which it is more difficult to recognize, especially if one is unaware of the possibility of this kind of complication. This R-L shunt seems to occur more frequently after a right-sided pneumonectomy. Important clinical clues suggestive for this complication are as follows: first, a relatively symptomless interval of a few months between the operation and the onset of symptoms; second, the posture dependency of the dyspnea, ie, the dyspnea becoming worse in the upright position (platypnea); and third, the volume dependency of the R-L shunt, ie, the shunt becoming worse in a dehydrated state. PMID- 8432149 TI - Occupational asthma induced by inhaled egg lysozyme. AB - A 26-year-old man employed in a company which manufactured hen egg white derived lysozyme for use in the pharmaceutical industry was evaluated for occupational asthma. The worker began to experience immediate-onset asthmatic symptoms two months after starting to work with egg lysozyme powder. The work process involved the production of approximately 1,000 kg of purified dried lysozyme powder per week. Prick skin testing was positive to egg lysozyme (50 mg/ml) and other egg protein components, but negative to whole egg white and egg yolk reagents. Serum specific IgE to egg lysozyme was documented. Decrements in serial peak expiratory flow rates were associated with lysozyme exposure at work. A specific bronchoprovocation challenge to lysozyme powder was positive demonstrating an isolated immediate asthmatic response (48 percent decrease from baseline FEV1). This is the first reported case of lysozyme-induced asthma specifically caused by inhalational exposure to egg lysozyme. PMID- 8432150 TI - The effect of pulmonary impairment on all-cause mortality in a national cohort. AB - The association between pulmonary impairment and all-cause mortality was investigated among white subjects in a follow-up study of a large national cohort. Pulmonary function was measured during the National Health and Nutrition Examination Survey (NHANESI) (1971 to 1975); subsequent mortality information was obtained from the 1987 NHANES I Epidemiologic Follow-up Study (1982 to 1987). Of 4,764 white sample persons, ages 25 to 74 years examined during NHANES I, 658 (13.8 percent) were identified as having pulmonary impairment defined as a FEV1/FVC < or = 69 percent. A total of 743 (15.6 percent) sample persons died during the follow-up period. The association between pulmonary impairment and all cause mortality was examined for male and female subjects separately using the Cox proportional hazards model controlling for age, smoking, educational level, body mass index, and respiratory diseases. The analysis suggests that reduced FEV1 percent predicted was a significant risk factor for mortality among both sexes, and the FEV1/FVC ratio was significantly associated with all-cause mortality among male subjects only. PMID- 8432151 TI - The effect of antibiotic therapy on recovery of intracellular bacteria from bronchoalveolar lavage in suspected ventilator-associated nosocomial pneumonia. AB - Intracellular bacteria (ICB) within recovered cells (> 7 percent) obtained via bronchoalveolar lavage (BAL) have been described as predictive of subsequent positive quantitative protected specimen brush (PSB) cultures in patients not receiving antibiotics. To determine the effect of prior or current antibiotic therapy on ICB relative to subsequent PSB culture, we prospectively evaluated 49 consecutive episodes of clinically suspected ventilator-associated pneumonia in 36 patients. Three patient groups were defined based on antibiotic administration: group 1 (current antibiotics), n = 31, samples obtained from patients currently receiving antibiotics; group 2 (recent antibiotics), n = 5, samples obtained from patients who received antibiotics > 48 h but < 72 h prior to sampling; and group 3 (no antibiotics), n = 13, samples from patients receiving no previous antibiotics within 7 days prior to sampling. Overall, PSB cultures (> or = 10(3) cfu/ml) were positive in 14 of 49 (29 percent) samples. In group 1, 2 of 31 (6 percent) samples were positive while 5 of 5 (100 percent) samples in group 2, and 7 of 13 (54 percent) in group 3 were positive. The presence or absence of ICB accurately predicted both positive and negative PSB cultures in 43 of 49 episodes. Of 43 correct predictions, 34 were negative predictions (negative ICB, negative PSB culture). The vast majority of these (29) were obtained from group 1, patients currently receiving antibiotics. In contrast, of nine positive predictions (+ICB, +PSB) virtually all (seven) occurred in group 3, patients receiving no antibiotics. In group 3, 13 of 13 PSB cultures were accurately predicted, either positive or negative, by the presence or absence of ICB. Of seven positive PSB cultures in groups 1 and 2, only 2 (28 percent) were accurately predicted by ICB. From both samples, the cultured organism was resistant to all administered antibiotics. These data suggest both prior and current antibiotic therapy reduces recovery of ICB from BAL and reduces predictive accuracy of ICB for subsequent positive PSB cultures. However, negative prediction by ICB for subsequent negative PSB cultures was good. In contrast, ICB obtained from patients not receiving antibiotics are highly predictive of subsequent PSB culture results, both positive and negative. We do not recommend BAL for evaluation of ICB in patients currently receiving antibiotics or with a recent history of antibiotic use. PMID- 8432152 TI - Evaluation of clinical judgment in the identification and treatment of nosocomial pneumonia in ventilated patients. AB - To evaluate the accuracy of clinical judgment in the diagnosis and treatment of nosocomial pneumonia in ventilated patients, we studied 84 patients suspected of having nosocomial pneumonia because of the presence of a new pulmonary infiltrate and purulent tracheal secretions. We prospectively evaluated the accuracy of diagnostic predictions and therapeutic plans independently formulated by a team of physicians aware of all clinical, radiologic and laboratory data, including the results of Gram-stained bronchial aspirates. Definite (n = 51) or probable (n = 33) diagnoses could be established in all patients by strict histopathologic and/or bacteriologic criteria. Only 27/84 patients were diagnosed as having pneumonia. Organisms responsible for pneumonias were identified by quantitative cultures of samples obtained using a protected specimen brush or pleural fluid cultures. Four hundred eight predictions were made for the 84 studied patients. Clinical diagnoses for patients subsequently diagnosed as having pneumonia were accurate in 81/131 cases (62 percent). Furthermore, only 43/131 (33 percent) therapeutic plans proposed for these patients represented effective therapy. Common causes of inappropriate treatment included failure to diagnose pneumonia (50 plans), failure to effectively treat highly resistant organisms (21 plans), and failure to treat all organisms in cases of polymicrobial pneumonia (14 plans). Therapeutic plans formulated for patients without pneumonia included the unnecessary use of antibiotics in 45/277 cases (16 percent). These findings indicate that the use of clinical criteria alone does not permit the accurate diagnosis of nosocomial pneumonia in ventilated patients, and commonly results in inappropriate or inadequate antibiotic therapy for these patients. PMID- 8432153 TI - Rate of decay or increment of PaO2 following a change in supplemental oxygen in mechanically ventilated patients with diffuse pneumonia. AB - It has been shown that patients with COPD require as long as 20 min for equilibration of oxygen tension to occur after changing the fraction of inspired oxygen (FIO2). To date, there have been no studies to determine the equilibration time for the PaO2 in mechanically ventilated patients with diffuse pneumonia. We studied seven patients (five males, two females) with radiographic evidence of diffuse pneumonia. All patients required mechanical ventilation. After introducing a change in FIO2, arterial blood gas values were measured at 5-min intervals for 30 min. Four patients achieved maximal change in PaO2 after 5 min, while four patients required 10 min. These results are similar to those found in patients with left ventricular failure who experience equilibration rapidly; however, patients with COPD experience it at a much slower pace. These observations have clinical importance when managing unstable patients where time is a critical element. PMID- 8432154 TI - Propofol vs midazolam in short-, medium-, and long-term sedation of critically ill patients. A cost-benefit analysis. AB - The purpose of this study was to evaluate and compare the clinical effects, safety, and economic cost of propofol and midazolam in the sedation of patients undergoing mechanical ventilation in the ICU. Eighty-eight critically ill patients were studied and randomly allocated to receive short-term (less than 24 h), medium-term (24 h to 7 days), and prolonged (more than 7 days) continuous sedation with propofol (n = 46) or midazolam (n = 42). Mean doses required were 2.36 mg/kg/h for propofol and 0.17 mg/kg/h for midazolam. Patients in the group receiving propofol showed a percentage of hours of sedation at the desired level (grade 2, 3, 4, or 5 on the Ramsay scale) of 93 percent, compared with 82 percent (p < 0.05) in the group receiving midazolam. Both agents were considered safe with respect to the induction of adverse reactions during their use in prolonged sedation. Recovery after interrupting sedation was significantly faster in patients treated with propofol than in those sedated with midazolam (p < 0.05). Recovery of total consciousness was predictable according to sedation time in propofol-treated subgroups (r = 0.98, 0.88, and 0.92, respectively), while this correlation was not observed in the midazolam-treated group. In the subgroup with sedation of less than 24 h, propofol provided a cost savings of approximately 2,000 pesetas (pts) per patient, due to shorter stays in the ICU. We conclude that propofol is a sedative agent with the same safety, higher clinical effectiveness, and a better cost-benefit ratio than midazolam in the continuous sedation of critically ill patients. PMID- 8432155 TI - Serum cytokine levels in human septic shock. Relation to multiple-system organ failure and mortality. AB - PURPOSE: Cytokines have been associated with the development of sepsis and diffuse tissue injury following septic or endotoxic challenges in humans. Furthermore, relative organ-system dysfunction, not specific organ dysfunction, appears to predict outcome from critical illness. We hypothesized that persistence of inflammatory cytokines within the circulation, reflecting a generalized systemic inflammatory response, is associated with multiple-system organ failure (MSOF) and death from critical illness. In addition, since hepatic function is central to host-defense homeostasis, we further reasoned that critically ill patients with hepatic cirrhosis would have an increased incidence of MSOF and death following sepsis associated with a persistence of cytokines in the blood. PATIENTS AND METHODS: We measured serum levels of tumor necrosis factor (TNF), interleukin (IL) 1, IL-2, IL-6, and interferon gamma (IFG) serially for the first 48 h following the onset of hypotension (systolic blood pressure < 90 mm Hg) thought likely to be due to sepsis in all patients presenting to one ICU. These data were correlated with initial severity of shock and retrospective determination of septic or nonseptic origin, preexistent hepatic cirrhosis, subsequent development of MSOF, and outcome. RESULTS: Fifty-three specific episodes of shock in 52 patients were recorded (35 septic and 18 nonseptic episodes). Mortality was higher in septic patients (41 vs 17 percent, p < 0.01), as was the development of MSOF (29 vs 6 percent, p < 0.001), incidence of cirrhosis (21 vs 0 percent, p < 0.01), and TNF levels over the study interval (p < 0.01). Nonseptic patients also had an initial elevation in TNF over 48-h levels (p < 0.05) that were higher than serum levels reported for normal subjects (chi 2, p < 0.05). There was no relation between peak TNF level and outcome. Sixty seven percent of the cirrhotic patients had development of MSOF and died, while only 30 percent of the noncirrhotic patients had development of MSOF or died (p < 0.05). The TNF and IL-6 levels in patients who had MSOF or who died were both elevated and did not decrease over time independent of presence or absence of sepsis (p < 0.01). Similarly, IL-6 levels after 12 h were higher in cirrhotic patients than in noncirrhotic septic patients (p < 0.05). No elevation in IL-1, IL-2, or IFG was seen in any patient subpopulation. CONCLUSIONS: TNF and IL-6 serum levels are higher in septic than in nonseptic shock, but the persistence of TNF and IL-6 in the serum rather than peak levels of cytokines predicts a poor outcome in patients with shock. PMID- 8432156 TI - Organophosphates and the heart. PMID- 8432157 TI - Multiple bilateral upper lobe cavitary lesions in a patient with inguinal diffuse large cell lymphoma. PMID- 8432158 TI - Lymphoma, neutropenia, and wheezing in a 70-year-old man. PMID- 8432159 TI - The effects of ventilator working pressure during pressure support ventilation. AB - The purpose of this study was to examine the consequences of altering ventilator working pressure on airway pressure and flow characteristics during pressure support ventilation (PSV). A ventilator (Siemens Servo 900C) and single lung simulator were used, and graphic read outs, in triplicate, were taken at a variety of combinations of PSV, working pressure, lung compliance, and airway resistance. The graphic read outs were then analyzed for a number of "dependent variables," and multiple regression analyses were performed using working pressure, PSV level, compliance, and resistance as "independent variables." The results show that the relative impact of working pressure on airway pressure and flow will vary with other lung and airway characteristics; also, excessive working pressure results in significantly greater flow rates at 40 ms after onset of inspiratory flow and at maximum flow, greater ringing or overshoot in the circuit, reduced tidal volume and inspiratory time, and reduced area under the airway pressure curve. In conclusion, adjusting ventilator working pressure will significantly affect lung-ventilator interaction in a quantifiable fashion. Further, these findings support clinical evidence that working pressure and/or initial flow rate need to be individualized to ensure optimal airway flow and pressure characteristics. PMID- 8432160 TI - Development of a new balloon catheter for management of hemoptysis with bronchofiberscopes. PMID- 8432161 TI - A revised system for analysis of abnormal pulmonary images. PMID- 8432162 TI - Diuretic-induced severe hyponatremia. Review and analysis of 129 reported patients. AB - Thiazides were responsible for severe diuretic-induced hyponatremia (serum sodium level < 115 mEq/L) in 94 percent of 129 cases reported in the literature between 1962 and 1990. The hyponatremia developed within 14 days in most of the patients receiving thiazides but in none of the patients who were treated with furosemide. Diuretic-induced hyponatremia was four times more common in women than in men. Advanced age was not associated with a higher tendency for hyponatremia. In the majority of the patients who received thiazides, excess antidiuretic hormone activity, hypokalemia, and excess water intake were accompanying findings which, singly or together, appeared to contribute to the development of hyponatremia. In 12 patients, mortality was directly related to hyponatremia. Rapid average correction of hyponatremia and a relatively high total correction (over 20 mEq/L) in the first 24 h were significantly associated with higher mortality or demyelinating syndrome. The presence of neurologic signs is an indication for active sodium replacement. The onset of thiazide-induced hyponatremia may in some cases occur within 1 day and therefore needs to be corrected rapidly, but within a total elevation of 20 mEq/L in the first 24 h. Where the onset is judged to have been slow (over several days), the level should be corrected at a slow rate, up to a total of 12 to 15 mEq/L in 24 h. PMID- 8432163 TI - Pathogenesis of hyponatremic encephalopathy. Current concepts. PMID- 8432164 TI - Cardiac rehabilitation in Switzerland. Efficacy of the residential approach following bypass surgery. AB - BACKGROUND: The traditional central European approach to cardiac rehabilitation involves sending patients to an idyllic setting, where they reside for a specified period following a cardiac event. Favorable results have been demonstrated using this approach in Germany, but to our knowledge no data have been reported from Switzerland, where these programs tend to be short (4 weeks) and exercise training is concentrated (2 h daily, 6 days per week). METHODS AND RESULTS: Seventeen patients (aged 58 +/- 6 years) who resided in a rehabilitation center for 4 weeks were compared with 11 patients (aged 54 +/- 7 years) given usual community care beginning approximately 6 weeks after coronary artery bypass surgery (CABS). Exercise training consisted of 1 h of group walking twice daily, with the intensity stratified into 4 levels based on clinical status and initial exercise capacity. All patients underwent pulmonary function testing and maximal ramp exercise testing on a cycle ergometer with continuous ventilatory gas exchange and lactate analysis before and after the study period. Patients receiving beta-blockers and those with cardiomyopathy or valvular heart disease were excluded. Medication status was not changed during the study period. Although maximal oxygen uptake increased by approximately 12 percent within both groups, the change was not significant between groups. Analysis of variance demonstrated that mean lactate levels were reduced throughout exercise within both groups (p < 0.001); however, there were no differences between groups. Oxygen uptake at the lactate threshold was not different in either group after the study period. CONCLUSIONS: Similar changes occur in the functional status of post-CABS patients regardless of their participation in the short but concentrated rehabilitation programs common in Switzerland, suggesting that these programs either begin too soon after CABS or are too short to achieve training benefits. PMID- 8432165 TI - Cholelithoptysis. A complication following laparoscopic cholecystectomy. AB - A 59-year-old woman who underwent laparoscopic cholecystectomy for symptomatic cholecystitis presented four months later with fever, malaise, anorexia, hemoptysis and lithoptysis. Chemical analysis of the expectorated lithes revealed them to be gallstones. Ultrasound studies of the right upper quadrant demonstrated both supradiaphragmatic and subdiaphragmatic fluid collections containing echogenic fragments. ERCP failed to demonstrate retained ductal stones or fistula formation. To our knowledge, this is the first reported case of cholelithoptysis and demonstrates an unusual complication of gallstone retention following laparoscopic cholecystectomy. PMID- 8432166 TI - Early diagnosis of traumatic thoracic aortic rupture by transesophageal echocardiography. AB - Traumatic aorta rupture survival depends on early diagnosis requiring aortography. Aortography is the "gold standard" method, but it is time-consuming and may be dangerous in trauma patients with multiple organ injuries. Transesophageal echocardiography is a noninvasive technology that can be performed at the bedside. We report two cases in which transesophageal echocardiography enabled us to make the early diagnosis of thoracic descending aorta rupture. PMID- 8432167 TI - Chronic brucella empyema. AB - Brucellosis rates have decreased in developed countries in recent years, but the pathologic condition still occurs in developing countries and well-known endemic areas such as the Mediterranean and Middle Eastern countries. A Portuguese patient presented in Switzerland with long-term pleural empyema, which was later diagnosed as Brucella empyema through positive cultures of Brucella melitensis. Brucellosis should be considered in patients who have traveled to Middle Eastern countries or any other areas where brucellosis is more frequently encountered. PMID- 8432168 TI - Tracheal occlusion from an intrathoracic stomach. AB - A patient presented with recurrent respiratory failure following esophagectomy. Systematic evaluation detected a previously unreported process causing this problem. Simple therapeutic measures were effective once the diagnosis was established. PMID- 8432169 TI - Levitating lung lesions due to bronchiolitis obliterans organizing pneumonia. AB - A 68-year-old man developed symmetrical bibasal infiltrates. Transbronchial lung biopsy specimen demonstrated abnormalities consistent with bronchiolitis obliterans organizing pneumonia (BOOP). The infiltrates appeared to migrate cephalad over a period of months, gradually disappearing after reaching the pulmonary apices. PMID- 8432170 TI - Fortuitous esophageal intubation. AB - Esophageal malposition is a potentially disastrous complication of attempted airway intubation. We report an unusual case in which a promptly recognized esophageal intubation aided detection of a perforated gastric ulcer. After the endotracheal tube was repositioned and the ulcer was surgically repaired, our patient had an excellent outcome. PMID- 8432171 TI - Retrieval of an aspirated bullet fragment by flexible bronchoscopy in a mechanically ventilated patient. AB - We report the case of a 28-year-old man who aspirated a bullet fragment following a gunshot. Review of the literature indicates this to be a rare finding. Bedside flexible bronchoscopy provided visualization of the foreign body and facilitated its removal while the patient was on a ventilator. The benefits of flexible bronchoscopy in similar conditions are discussed. PMID- 8432173 TI - MR and CT diagnosis of carcinoid heart disease. AB - This report describes findings present on magnetic resonance (MR) imaging and computed tomography (CT) in a patient with carcinoid heart disease. Major abnormalities included thickening and immobility of the tricuspid valve leaflets and disturbed flow patterns indicative of tricuspid stenosis and regurgitation demonstrated with cine MR. While echocardiography is usually the initial imaging modality in patients with carcinoid heart disease, other modalities such as MR and CT may provide correlative or supplemental information. PMID- 8432172 TI - Bleeding varices due to portal hypertension in sarcoidosis. Favorable effect of propranolol and prednisone. AB - A 58-year-old white man had bleeding varices in the gastric fundus due to portal hypertension attributable to histologically proven hepatic sarcoid involvement with a giant splenomegaly and with an angiographically demonstrated significant flow toward the liver. Treatment with corticosteroids and beta-blockade (30 mg propranolol daily) resulted in no rebleeding for over one year follow-up. PMID- 8432174 TI - Farmer's fever. Systemic manifestation of farmer's lung without lung involvement. AB - A 35-year-old dairy farmer presented with recurrent febrile episodes over more than three years. Fever up to 39 degrees C occurred only if he was in contact with the dairy barn and typically appeared at 4 to 8 h after an otherwise usual barn exposure. He had no dyspnea and throughout this period repeated physical examinations, chest roentgenograms, and lung functions remained normal. He was bronchoscoped and lavaged on three occasions, a lymphocytic alveolitis was always present and once, immediately after an acute episode, an important increase in lavage neutrophils was also found (47 percent). Transbronchial lung biopsy specimens showed a moderate cellular infiltrate but no granuloma or fibrosis. Three other persons who worked at the same farm had no similar manifestations or respiratory illnesses. The patient therefore had typical systemic manifestations of acute farmer's lung, but without the lung involvement required to confirm that diagnosis. Furthermore, his disease does not fit the entities known as grain fever and organic dust toxic syndrome. We believe that this patient presented a different entity that we coined "farmer's fever." PMID- 8432175 TI - Pulmonary hemorrhage in association with autoimmune chronic active hepatitis. AB - Extrahepatic manifestations have been reported in a majority of patients with ACAH. We describe an 11-year-old girl with CAH who developed life-threatening AH and was successfully managed with mechanical ventilation and high-dose steroids. Although a number of pulmonary manifestations have been described in association with AICAH, this article is the first showing its association with AH. PMID- 8432176 TI - Pneumoblastoma in neurofibromatosis. AB - Pneumoblastoma is a rare tumor composed of two histologic cell types, arising from epithelium and stroma. Patients with von Recklinghausen's disease are known to develop certain types of tumors. A rare, and possibly first case of pneumoblastoma arising in a patient with neurofibromatosis is described. PMID- 8432177 TI - Idiopathic hemothorax. AB - Development of spontaneous hemothorax without predisposing conditions is extremely rare. We report a young man with a history of a seizure disorder who presented to the emergency department with spontaneous hemothorax. Exploratory thoracotomy evacuated 2,000 ml of old blood. No source of hemorrhage was identified. To our knowledge, this is the first report of spontaneous hemothorax proved by thoracotomy. PMID- 8432178 TI - Cardiac abscess following percutaneous transluminal coronary angioplasty. AB - We report the first case of myocardial abscess directly related to percutaneous transluminal angioplasty (PTCA). Infectious complications of PTCA are very rare and limited to a few cases of groin infection and septic endarteritis most often after repeated procedures. In our patient, a problematic and repeated procedure probably led to a direct colonization and subsequent infection of an intimal dissection of the right coronary artery. Standard aseptic techniques can be inadequate in the case of early repuncture or if there is an indwelling line. Prophylactic antibiotic treatment should be considered in this case, although its usefulness has not been yet formally demonstrated. PMID- 8432179 TI - Cardiac tamponade due to Nocardia asteroides. AB - Pericarditis with hemodynamic compromise is a rare manifestation of infection with Nocardia asteroides. To our knowledge, only six cases have been reported previously. In contrast to other cases of pericardial disease due to Nocardia, culture of the pericardial fluid in our case was negative while culture of pericardial tissue led to the diagnosis. Surgical intervention and appropriate antibiotic therapy are essential in the treatment of Nocardia pericarditis. PMID- 8432180 TI - Pulmonary hypertension secondary to thrombocytosis in a patient with myeloid metaplasia. AB - A 72-year-old physician with myeloid metaplasia developed marked thrombocytosis, pulmonary hypertension, and right heart failure following splenectomy. No cause for the pulmonary hypertension could be found. The pulmonary hypertension and right heart failure returned to normal when hydroxyurea therapy corrected the thrombocythemia. It is concluded that thrombocytosis may cause pulmonary hypertension, mediated by pulmonary capillary obstruction from cellular components, involving platelet aggregation, microthrombosis, and stasis, and possible vasoconstrictor effects. PMID- 8432181 TI - Focal pulmonary embolism presenting as diffuse pulmonary edema. AB - We report the unique occurrence of bilateral pulmonary edema in a patient with a small focal pulmonary embolus without evidence of underlying cardiac or pulmonary disease. The most likely mechanism for this involves the release of humoral factors leading to extravasation of fluid across pulmonary capillary membranes. This case illustrates that pulmonary emboli should always be considered in the differential diagnosis of pulmonary edema. PMID- 8432182 TI - Concurrent catamenial hemothorax and hemopneumothorax. AB - We describe a case of catamenial hemothorax and hemopneumothorax occurring on both sides simultaneously; the patient responded remarkably with danazol therapy. To our knowledge, this is previously unreported in the literature. PMID- 8432183 TI - Acquired immunodeficiency syndrome-related visceral leishmaniasis presenting in a pleural effusion. AB - Visceral leishmaniasis is increasingly reported in immunocompromised patients, including patients with AIDS. We report a case of visceral leishmaniasis in an AIDS patient who presented with pulmonary symptoms and bilateral pleural effusions. Histologic evaluation of pleural fluid and bone marrow revealed histiocytes with intracellular Leishmania amastigotes. Visceral leishmaniasis should be considered in AIDS patients with a significant travel history who present with unexplained pulmonary symptoms. PMID- 8432184 TI - Radiotherapy: an effective treatment of cerebral involvement by lymphomatoid granulomatosis. AB - We report the case of a 40-year-old woman who presented with neurologic complications of lymphomatoid granulomatosis after an initial pulmonary presentation. After treatment failure with immunosuppressive therapy, she responded dramatically to cranial radiation therapy without prior surgery. PMID- 8432185 TI - Sleep studies in OSA patients before CPAP treatment. One night or two? PMID- 8432186 TI - Boa constrictor. PMID- 8432187 TI - Cervical injury causing widening of the mediastinum. PMID- 8432188 TI - Small-volume nebulizers versus metered-dose inhalers. PMID- 8432189 TI - Chylous transport of amiodarone. PMID- 8432190 TI - Definitions for sepsis and organ failure. The ACCP/SCCM Consensus Conference Committee Report. PMID- 8432191 TI - Meiotic analysis by FISH of a human male 46,XY,t(15;20)(q11.2;q11.2) translocation heterozygote: quadrivalent configuration, orientation and first meiotic segregation. AB - Understanding the segregational behaviour of reciprocal translocations in man is of both theoretical and clinical importance. Generally, information for genetic counselling is obtained from empirical data although knowledge of gametic output can now be obtained by karyotyping individual human spermatozoa. However, neither empirical studies nor sperm karyotyping data provide detailed information on how the combinations of normal, balanced and unbalanced gametes arise. For this knowledge of quadrivalent orientation and first meiotic segregation is required. We have used dual colour fluorescence in situ hybridisation (FISH) to identify normal and derived chromosomes during meiosis in testicular biopsy material from a 46,XY,t(15;20)(q11.2;q11.2) heterozygote. We were able to determine the frequencies of different quadrivalent structures at first metaphase (MI) and the proportion of first meiotic divisions subject to interstitial chiasmata. Having identified all 2:2, 3:1 and 4:0 segregation products at second metaphase, it was possible to correlate segregation categories with the various forms of MI quadrivalent possibly indicating their modes of orientation. Finally the ratios of normal:balanced:unbalanced gametes expected to be produced by this translocation heterozygote were calculated. PMID- 8432192 TI - Molecular characterization of a pericentric inversion in mouse chromosome 8 implicates telomeres as promoters of meiotic recombination. AB - A "hot spot" of meiotic recombination has been found in males on murine chromosome 8 using nonisotopic hybridization of a series of probes to mitotic and meiotic chromosomes. The sequences responsible for this enhanced recombination are the telomeric repeats. Mice both normal and hetero- or homozygous for a pericentric inversion, In(8)1 Rl, were analyzed. The inversion subdivides chromosome 8 into three discreet regions: (1) a fraction of the micro "short arm" that contains 30-150 kb of telomeric sequences and only about one-fifth of the contiguous minor-satellite sequences (approximately 200 kb); (2) the inverted region; and (3) the noninverted distal two-thirds of the chromosome. In 70 spermatocytes from inversion heterozygotes, examined by electron microscopy, synapsis of the inverted region was complete but entirely nonhomologous. Nonhomologous synapsis persists from initiation of synaptonemal complex formation in zygonema/early pachynema until dissolution in late pachynema. This nonhomologous synapsis also suppresses crossing over within the inverted segment. The opportunity for proximal homologous recombination is thus restricted to the roughly 250 kb segment located between the short-arm break and the end of the bivalent. Nonetheless, an extreme proximal chiasma was observed in 11% of the heterozygous chromosome-8 bivalents, 34% of the normal 8 bivalents and 35% of the homozygous inversion 8 bivalents from spermatocyte preparations. Since in the normal chromosomes all minor satellite sequences are adjacent to the telomere, while in the inversion chromosomes most of these sequences are transposed to an interstitial position without a corresponding shift in chiasma position, the minor-satellite sequences can be ruled out as promoters of recombination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8432193 TI - Telomeric structure in cells with chromosome end associations. AB - End-to-end associations of metaphase chromosomes have been observed in a variety of human tumors, ageing cells, and several chromosome instability syndromes. Since telomeres of tumor cells and ageing tissues are often reduced in length, it has been suggested that chromosome end associations may be due to loss of telomeric repeats. We report the molecular structure of telomeres of two human tumor cell lines with frequent end-to-end associations of metaphase chromosomes. These telomeres were shown to be severely reduced compared with most other human cells with functional telomeres. However, we also describe two cell lines with severely shortened telomeres that are not detectably compromised in their function. We suggest that telomeric length is not the only determinant of the fusigenic behavior of human telomeres in tumor cells. PMID- 8432194 TI - The replication behavior of Saccharomyces cerevisiae DNA in human cells. AB - We studied the replication of random genomic DNA fragments from Saccharomyces cerevisiae in a long-term assay in human cells. Plasmids carrying large yeast DNA fragments were able to replicate autonomously in human cells. Efficiency of replication of yeast DNA fragments was comparable to that of similarly sized human DNA fragments and better than that of bacterial DNA. This result suggests that yeast genomic DNA contains sequence information needed for replication in human cells. To examine whether DNA replication in human cells would initiate specifically at a yeast origin of replication, we monitored initiation on a plasmid containing the yeast 2-micron autonomously replicating sequence (ARS) in yeast and human cells. We found that while replication initiates at the 2-micron ARS in yeast, it does not preferentially initiate at the ARS in human cells. This result suggests that the sequences that direct site specific replication initiation in yeast do not function in the same way in human cells, which initiate replication at a broader range of sequences. PMID- 8432195 TI - Electron microscope tomography of Balbiani Ring hnRNP substructure. AB - Three-dimensional (3-D) reconstructions, by electron microscope tomography, of selectively stained, contrast enhanced Balbiani Ring (BR) hnRNP granules reveal a complex spatial arrangement of RNA-rich domains. This particulate substructure was examined by volume rendering computer graphics. Modeling the arrangement of RNA-rich domains is made difficult by apparent structural flexibility and/or heterogeneity of composition. Formulation of a consensus 3-D arrangement of RNA rich domains will require an expanded data base of reconstructed BR granules and the development of new image manipulation and analysis techniques. This study demonstrates the potential for ultrastructural cell biology of combining several new techniques: selective nucleic acid staining, electron spectroscopic imaging to enhance contrast, electron microscope tomography and volume rendering computer graphics. PMID- 8432197 TI - Effect of random abnormal cell proportion on specimen classifier performance. AB - A series of papers had analyzed a simplified model of an automated cytology prescreening configuration consisting of a two-class cell classifier followed by a two-class specimen classifier. This has shown, among other things, that the proportion (p) of abnormal cells on an abnormal specimen dictates the number (N) of cells that must be classified before the specimen can be classified with specified accuracy (Anal Quant Cytol, 2:117-122, 1980). It has also shown that if a system designed assuming one fixed value, po, encounters a specimen with a different fixed value, p, then the specimen classifier false negative rate will deviate significantly from the design value, increasing for p < po and vice versa (Cytometry, 2: 155-158, 1981). Using a Gaussian approximation, Timmers and Gelsema (Cytometry, 6:22-25, 1985) extended this to the case where p is a Beta distributed random variable. They showed that N increases dramatically with the width (coefficient of variation) of the distribution of p. They also concluded that the randomness of p imposes a fundamental lower limit on the specimen false negative rate below which it is impossible to go, even with an error-free cell classifier. In this paper we also extend the basic model to cover the case of random p, but by using an asymptotic expansion (rather than the Gaussian approximation), to develop an expression for N. We show that the limit cited by Timmers and Gelsema is not real, but is actually an artifact of the breakdown of the Gaussian approximation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8432196 TI - Sex chromosomes, recombination, and chromatin conformation. AB - We review what is known about the transcriptional inactivation and condensation of heteromorphic sex chromosomes in contrast to the activation of homomorphic sex chromosomes during meiotic prephase in animals. We relate these cytological and transcriptional features to the recombination status of the sex chromosomes. We propose that sex chromosome condensation is a meiotic adaptation to prevent the initiation of potentially damaging recombination events in nonhomologous regions of the X and Y chromosome. PMID- 8432198 TI - Microscopic analysis of interactions between HIV particles and living leukocytes. AB - Video-enhanced/-intensified optical microscopy has been used to study the interaction of non-infectious HIV8E5 particles with living cells. The purified particles retained gp120 antigenic sites. Fluorescent lipids were intercalated into the particles' envelopes. When incubated with CD4+ cell lines, roughly 90% of the cells bound HIV8E5 particles. The extent of fusion and endocytosis varied among the cell lines tested. CD4- control cells did not significantly bind, fuse, or internalize particles. To control for non-specific exchange of the fluorescent label, HIV8E5 were bound to CD4- murine WEHI cells using concanavalin A; no apparent fusion or internalization took place. We suggest that both fusion and internalization are important mechanisms of virion-cell interaction. Adherent human peripheral blood mononuclear cells were much less efficient in binding HIV8E5 than non-adherent mononuclear cells. Both endocytosis and apparent fusion were observed for lymphocytes. Our results indicate that cells interact with HIV8E5 by multiple pathways and that these pathways are strongly affected by cell type (lymphocyte or monocyte) and origin (normal or transformed). These methods may be useful in characterizing viral entry and in anti-viral drug screening. PMID- 8432199 TI - Flow cytometric titration of retroviral expression vectors: comparison of methods for analysis of immunofluorescence histograms derived from cells expressing low antigen levels. AB - Few quantitative studies addressing immunofluorescence histogram analysis have been published. One study by Overton (Cytometry 9:619-626, 1988) has shown threshold and histogram subtraction methods to be accurate for analysis of well separated immunofluorescence distributions of positive and negative cells. An evaluation of methods to analyze immunofluorescence histograms when positive and negative immunofluorescence distributions overlap has not, to our knowledge, been reported. In this paper, data obtained from flow cytometry of immunofluorescently stained cells infected with recombinant retroviruses that produce a range of simian virus 40 large T antigen levels were analyzed by threshold, histogram subtraction, and distribution modeling methods. This analysis showed that as the separation between the immunofluorescence distributions of positive and negative cell populations decrease the best methods for histogram analysis are modeling followed, in order, by histogram subtraction, and threshold analysis. PMID- 8432200 TI - Flow cytometric quantitation of nucleoside transporter sites on human leukemic cells. AB - Quantitation of equilibrative, nitrobenzylthioinosine (NBMPR) sensitive (es) nucleoside transporters on blast cells isolated from patients with acute myeloblastic leukemia is useful in predicting intracellular accumulation of the antileukemic nucleoside drug, cytosine arabinoside. We previously reported the synthesis of a fluorescein-labeled ligand for the es nucleoside transporter, 5 (SAENTA-x2)-fluorescein. This paper reports the synthesis of 5-(SAENTA-x8) fluorescein in which the linkage between fluorescein and nucleoside ligand has been increased from 2 atoms to 8 atoms. This new ligand had a sixfold increase in affinity (Kd 0.9 +/- 0.1 nM) as well as an 86% increase in the cell associated fluorescence output compared to its prototype 5-(SAENTA-x2)-fluorescein. The fluorescence signal arising from 5-(SAENTA-x8)-fluorescein specifically bound to freshly isolated and cultured leukemic myeloblasts was converted to molecules of equivalent soluble fluorescein (MESF) using standardized fluorescein microbeads and compared with the number of es nucleoside transporter sites assayed concurrently by [3H]NBMPR equilibrium binding analysis. A high correlation between the two assays was observed (r = 0.98), which enabled the cell-bound fluorescence output of 5-(SAENTA-x8)-fluorescein to be expressed in numbers of es nucleoside transporter sites per cell. The improved properties of 5-(SAENTA-x8) fluorescein over those of its prototype molecule make it a suitable reagent for flow cytometric quantitation of nucleoside transporter expression on leukemic cells isolated from patient samples. PMID- 8432201 TI - Cytofluorometric assay for the determination of thymidine uptake and phosphorylation in living cells. AB - Thymidine kinase is a key enzyme for the application of drugs in chemotherapy and for diagnosis. Although of great interest, its regulation during cell cycle and differentiation is difficult to study, as current techniques for isolation of cells in different phases of growth are unsatisfactory. An assay that allows the determination of enzymatic activity in situ in single cells would be much faster than present methods and would elegantly avoid synchronization procedures. We synthesized different analogues of thymidine with the 5-methyl group substituted by a fluorochrome. At least three of these compounds were phosphorylated by thymidine kinase in cell free extracts and were taken up and phosphorylated by cells in culture. The cytofluorometric signal of the accumulated fluorochrome in any given cell reflected the thymidine kinase activity of this cell. Simultaneous measurement of cell-cycle dependent parameters allowed the correlation of thymidine kinase activity with the phase of growth in mixed cell populations. PMID- 8432202 TI - Expression of silver-stained nucleolar organizer regions is coupled to cell cycle in rat thymic cells. AB - To directly analyze the relationship between the expression of silver-stained nucleolar organizer regions (AgNORs) and cell proliferation, thymic cells from newborn rats were separately sorted at the G0-G1-phase and early-mid and late-mid S-phase of the cell cycle according to their DNA content. Different AgNOR-derived parameters (mean area and numbers of AgNORs per cell and mean AgNOR-particle area) were evaluated after silver staining of cytospins. A linear correlation was observed between the mean area and numbers of AgNORs per cell, both parameters increasing progressively from G0-G1-phase to early-mid and late-mid S-phase. An increase of the mean AgNOR-particle area was also seen between G0-G1 and S-phase but this was not significant along the S-phase. A bias on the selection of S phase cells linked to intrathymic maturation can be ruled out as S-phase cells labeled with bromodeoxyuridine were found throughout the thymus, and, moreover, the analysis of the frequency distribution of nuclear area did not show a bimodal pattern. It is concluded that the expression of AgNORs--evaluated as AgNOR area/cell or AgNOR numbers/cell--is causally or indirectly coupled to DNA synthesis and, thus, AgNORs can be considered as a cell proliferation marker. PMID- 8432203 TI - Increased sensitivity of damaged DNA to digestion with nuclease S1 as assessed in single cells by flow cytometry. AB - DNA sensitivity to digestion with nuclease S1 was investigated in cells irradiated with gamma rays, or treated with the antitumor drug adriamycin (Adr). The nuclease-resistant DNA fraction was determined by propidium iodide staining. Treated cells were found to be more sensitive to nuclease digestion than the undamaged controls. Gamma ray-induced strand breaks were detectable at doses up to 10 Gy; an increase in the reaction temperature, from 37 degrees to 63 degrees C, was necessary in order to detect higher levels of damage. Nuclease S1 sensitivity in Adr-treated cells showed a single-peak, concentration-dependent relationship, in agreement with the known self-inhibitory effect exerted by high drug doses. Determination of DNA digestion could be performed in combination with other cellular parameters (e.g., protein content). Detection of drug-resistant cells in a heterogeneous population of small-cell lung carcinoma was achieved on the basis of the different sensitivity of the cells to enzymatic digestion. These results indicate that nuclease S1 may be a useful probe for studying in single cells DNA alterations induced by drugs or radiation. PMID- 8432204 TI - Flow cytometric analysis of altered mononuclear cell transmembrane potential induced by cyclosporin. AB - Immunosuppression by the fungal metabolite cyclosporin A (CsA) is characterized by functional inhibition, rather than destruction of cells. Because activation of immune cells involves intracellular signalling events associated with modulations of cell transmembrane potential (TMP), we tested the ability of cyclosporin A (CsA) to modulate immune mononuclear cell TMP in vitro using a TMP sensitive cationic dye, dihexyloxacarbocyanine (DIOC6(3)). All analyses were performed by flow cytometry. CsA increased TMP in monocytes and lymphocytes isolated from the blood of healthy human volunteers. CsA-induced hyperpolarization was time and concentration dependent in monocytes while the lymphocyte hyperpolarization, although time dependent, was evident over the entire range of CsA concentrations tested. CsA-induced hyperpolarization of lymphocytes was dependent on potassium ion (K+) efflux as indicated by the absence of hyperpolarization in 154 mM KCl or with pretreatment with 100 microM quinine (an inhibitor of K+ channels). Monocyte hyperpolarization by CsA was not inhibited in either system. Dihydrocyclosporin C (DH-CsC), an immunosuppressive analog of CsA, also hyperpolarized mononuclear cells. The anionic TMP sensitive dye bis oxonal (diBA-C4) indicated that CsA treatment depolarized mononuclear cell plasma membranes. The mitochondrial poison carbonyl cyanide p-trifluoromethoxy-phenyl-hydrazine (FCCP) eliminated CsA induced hyperpolarization and also indicated that CsA caused plasma membrane depolarization. We conclude that brief in vitro exposure to cyclosporin alters the transmembrane electrical potential of human lymphocytes and monocytes. PMID- 8432205 TI - Rhodamine 123 fluorescence of immortal hybridoma cell lines as a function of glucose concentration. AB - The fluorescence of rhodamine 123 stained cells has been described to specifically reflect the activity of mitochondria. Changes in the intensity of fluorescence observed in stimulated lymphocytes were attributed to an increased glycolytic activity of cells due to increased growth rates. Previously reported changes in mitochondrial activity observed in batch cultures were likewise attributed to changed growth rates. In this study we report that the Rh123 fluorescence of hybridoma cell lines in batch culture more closely correlates to the glucose concentration in the culture supernatant than to growth rates. When cells are transferred into glutamine free medium with defined glucose concentrations ranging from 0 to 3,000 mg/L the mean Rh123 fluorescence adapts to the respective glucose concentration within 6 hours and gives a linear correlation. This can be explained by the previously described dependence of specific glucose consumption rates on glucose availability in the medium. The importance of controlling glucose availability, especially in large scale fermentations, is discussed. PMID- 8432206 TI - Neural Network Analysis of DNA flow cytometry histograms. AB - A pattern recognition system based on Neural Network Analysis, a form of artificial intelligence, was used to search DNA flow cytometry histograms for features that correlated with breast cancer patients' risk of relapse. DNA flow cytometry histograms and clinical follow-up information from 796 breast cancer patients were used to train a Neural Network to predict the clinical outcome of patients in a separate independent set of 794 patients. Median follow-up in this patient data base was short, 23 months. Neural Network Analysis resulted in a model that evaluated DNA flow cytometry histograms differently than conventional analysis, which categorizes the histograms by ploidy and S-phase fraction. Neural Network Analysis appeared to identify low risk and high risk subsets of patients as accurately as conventional analysis. Neural Network Analysis placed heavy emphasis on the region to the right of the diploid G2/M peak, where a subpopulation of nuclei with high DNA content is seen even in many histograms scored as diploid by conventional techniques. The number of nuclei in this region was found to be a powerful predictor of patient outcome, and multivariate analysis showed that the number of nuclei in this region and the S-phase fraction both were independently predictive of relapse. This pilot study suggests that conventional analysis (based on a mechanistic interpretation of regions in flow cytometry histograms) might be used in conjunction with and improved by pattern recognition systems or insights derived from them. PMID- 8432207 TI - Cytometric analysis of blood cells from malaria-infected patients and in vitro infected blood. AB - Blood samples from malaria-infected patients and from in vitro culture were analyzed using the H*1 hematology analyzer. An attempt to find a hematologic parameter for detecting the malaria infection and to characterize the pathophysiological changes of red cells was made. The study included 18 malaria infected patients (10 with Plasmodium falciparum and 8 with Plasmodium vivax) and 52 normal, healthy volunteers. Increased young large lymphocyte or large unstained cell count (LUC over 3%) in the peripheral blood of malaria-infected patients was evidence for malaria infection. Increased population dispersions of red cell volume (red cell distribution width: RDW) and intraerythrocytic hemoglobin concentration (hemoglobin distribution width: HDW) were demonstrated both in clinical samples and cultured blood. The increased RDW correlated with an increased percentage of macrocytes (r = 0.64, P = 0.004). Comparison of HDW and percentage of hypochromic red cells between the clinical specimen and the cultured blood supports the finding that changes in red cell hemoglobin concentration were mainly due to the response of the patient to malaria infection and partly due to the effect of malaria parasites on the red cells. PMID- 8432208 TI - Quantification of fluorescence properties of lymphocytes in peripheral blood mononuclear cell suspensions using a latent class model. AB - Lymphocytes, monocytes, granulocytes, and other blood cells can be distinguished on the basis of their forward (FSC) and sideward (SSC) light scatter properties and their expression of CD45 and CD14. A FSC,SSC gate can be set to include > 95% of the lymphocytes using a "back gating" procedure on the CD45+, CD14- cells. However, nonlymphoid cells such as monocytes have light scattering properties similar to lymphocytes. This problem occurs particularly in patient populations where the light scattering properties of lymphocyte subsets have changed (e.g., due to activation) and are similar to those of the monocytes. Thus, immunophenotyping using antibodies specific for other markers than CD45 and CD14 does not allow a direct assessment of the percentage of all lymphocytes positive for those markers. In order to optimize immunophenotyping we have developed analytic model in which the FSC,SSC dot plot is partitioned into six nonoverlapping light scatter regions. Each light scatter region contains a mixture population of different cell types, i.e., lymphocytes, monocytes, granulocytes, and other cells. The proportions of each cell type are known from the CD45,CD14 expression within each light scatter region. Under the assumption of independence of fluorescence and scatter properties conditional on cell type, the expression of markers other than CD45 or CD14 are derived from the cell type composition and the fluorescence properties on the other markers of each light scatter region. The underlying statistical model is a latent class model, and maximum likelihood estimates are computed using the expectation-maximization (EM) algorithm. The application of the model for immunophenotyping of lymphocytes of healthy individuals and cancer patients receiving immunotherapy is shown. PMID- 8432209 TI - Detection of male cells in mixtures containing varying proportions of male and female cells by fluorescence in situ hybridization and G-banding. AB - The efficiency and sensitivity of fluorescence in situ hybridization (FISH) and G banding for the detection of male cells in mixtures of male and female cells derived from peripheral blood (PB) and bone marrow (BM) are compared. Zero false positive and negative rates were obtained with G-banding in all studies. False positive rates obtained with FISH were low (0-2.5%) in both PB and BM. False negative rates varied from 0-13.3%. Variations due to differences in fluorescent counterstain or scorers were not significant and in some cases the percentage of Y-positive cells as determined by FISH agreed more closely with the estimated frequency of male cells than that obtained by G-banding. The minimum limits of detection for FISH were 5% male cells on counting 500 PB or BM interphases; 10% male cells on counting 100 PB metaphases; and 20% male cells on counting 50 BM metaphases. This is in agreement with the theoretical limits of detection [95% confidence limit (CL)]. However, minimum levels of detection for female cells were below the 95% CL. It was not possible to reliably distinguish 95% female cells from 100% on counting 500 PB or BM interphases; 90% from 100% on counting 100 PB metaphases; or 80% from 100% on counting 50 BM metaphases. PMID- 8432210 TI - Chromatid contamination can impair the purity of flow-sorted metaphase chromosomes. AB - We describe a phenomenon where a second flow karyotype is superimposed on the normal metaphase flow karyotype of human lymphoblastoid chromosomes. The events of this second flow karyotype contain half the DNA content of corresponding events in the normal flow karyotype and, when sorted, show the morphology of single chromatids. DNA amplified by degenerate oligonucleotide-primed PCR of 300 chromatids sorted from a single peak and hybridized onto normal metaphase spreads painted the entire length of the corresponding chromosome type. In retrospect, we could observe this phenomenon at a low level in 37% of randomly selected, previously analyzed flow karyotypes and in several published flow karyotypes from other laboratories. Experimentally, chromatid frequency was shown to vary with the colcemid blocking conditions as well as with the cell line used. At the extreme, we obtained a 4:10 ratio of chromatids to metaphase chromosomes, whereas this could be reduced tenfold by altering the colcemid blocking conditions in the same cell line. The presence of chromatids in chromosome preparations has important implications for the purity of isolated fractions used for generating libraries and in PCR analysis. PMID- 8432212 TI - Effect of cold remedies on metabolic control of NIDDM. AB - OBJECTIVE: To compare the effects of two cough syrup formulations (one with sugar and alcohol and one without) on the metabolic control of NIDDM. RESEARCH DESIGN AND METHODS: A prospective, blinded cross-over study was performed at the Endocrinology Clinic of a U.S. Army Medical Center on 20 volunteers with NIDDM, treated with diet alone or diet plus an oral hypoglycemic agent. After a 7-day lead-in period, patients took 3-day courses of each cough syrup (10 ml 4 times/day) with an intervening 4-day wash-out period. Fasting and postprandial blood glucose and lipids before and immediately after each course were compared. RESULTS: No differences in pretherapy and posttherapy values were found with either formula. Values taken after the sugar- and alcohol-containing formula were not different from those taken after the alcohol- and sugar-free formula. CONCLUSIONS: We conclude that patients with NIDDM can take standard daytime cough formulas, in short courses of standard doses, without adverse effect on blood glucose or lipids. PMID- 8432211 TI - The relationship of physical fitness to lipid and lipoprotein(a) levels in adolescents with IDDM. AB - OBJECTIVE--Increased physical activity and physical fitness are recommended therapeutic modalities in addition to insulin and diet in the management of children with IDDM. The aim of this study was to assess the fitness levels of adolescents with IDDM compared with healthy control subjects and to evaluate the relationship between physical fitness and metabolic control. RESEARCH DESIGN AND METHODS--We studied 59 patients with IDDM, 28 boys and 31 girls, age 15.6 +/- 2.5 yr, duration of diabetes 7.6 +/- 3.5 yr, HbA1 10.6 +/- 2.1% (mean +/- SD), and compared them with 18 healthy, nondiabetic control subjects, 9 boys and 9 girls, matched for age, BMI, and Tanner stage. Physical fitness was measured by VO2max during progressive bicycle ergometry. HbA1 was used to determine glycemic control. Lipid profile included fasting total cholesterol, HDL, LDL, Lp(a), and TG levels. RESULTS--Patients with IDDM had lower VO2max levels than control subjects (33.7 +/- 7.0 vs. 41.0 +/- 10.4 ml.kg-1.min-1, P = 0.001). Males with IDDM had lower VO2max than male control subjects, but diabetic and control females showed no difference. In IDDM patients, VO2max correlated inversely with HbA1, insulin dose, cholesterol, LDL, TGs, and Lp(a), but did not correlate with HDL, which correlated inversely with BMI. CONCLUSIONS--We conclude that the state of physical fitness is an important correlate of lipid levels and Lp(a) in adolescents with IDDM. We speculate that higher physical fitness levels in adolescents with IDDM may decrease the risk of CVD through modulating lipid levels. PMID- 8432213 TI - HLA-DQ associations distinguish insulin-resistant and insulin-sensitive variants of NIDDM in black Americans. AB - OBJECTIVE: NIDDM in black Americans exists as two variants: one with a primary defect in insulin action (insulin-resistant variant) and the other with normal insulin action and a primary defect in insulin secretion (insulin-sensitive variant). The objective of this study was to determine whether these two variants were genetically distinct from each other and from normal control subjects as determined by HLA typing. RESEARCH DESIGN AND METHODS: Insulin action was measured with the euglycemic insulin clamp with a 1 mU.kg-1.min-1 insulin infusion with [3-3H]glucose. A glucose disposal of < 278 mumol.kg-1.min-1 was considered insulin resistant, and a value greater than this was considered insulin sensitive. The study population consisted of 21 insulin-resistant and 25 insulin-sensitive black NIDDM patients and 89 normal, nondiabetic black control subjects from an urban hospital. HLA typing was performed with serological methods. RESULTS: The frequency of HLA-DQW7 in the insulin-resistant population (76%) was significantly greater than that in the insulin-sensitive population (32%, corrected P < 0.018) and the normal control population (21%, corrected P < 0.001). The frequency of HLA-DQW6 was increased in the insulin-sensitive population (76%), corrected P < 0.023, as compared with the normal control subjects (33%). The relative risk of HLA-DQW7 in identifying insulin-resistant NIDDM patients compared with control subjects was 7. CONCLUSIONS: At least one component that differentiates insulin-resistant and insulin-sensitive NIDDM in black Americans is under different genetic control. One or more loci responsible for insulin-resistant and insulin-sensitive NIDDM are likely to be in linkage disequilibrium with the DQ locus of the human MHC region of chromosome 6. PMID- 8432214 TI - Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. AB - OBJECTIVE: To assess predictors of CVD mortality among men with and without diabetes and to assess the independent effect of diabetes on the risk of CVD death. RESEARCH DESIGN AND METHODS: Participants in this cohort study were screened from 1973 to 1975; vital status has been ascertained over an average of 12 yr of follow-up (range 11-13 yr). Participants were 347,978 men aged 35-57 yr, screened in 20 centers for MRFIT. The outcome measure was CVD mortality. RESULTS: Among 5163 men who reported taking medication for diabetes, 1092 deaths (603 CVD deaths) occurred in an average of 12 yr of follow-up. Among 342,815 men not taking medication for diabetes, 20,867 deaths were identified, 8965 ascribed to CVD. Absolute risk of CVD death was much higher for diabetic than nondiabetic men of every age stratum, ethnic background, and risk factor level--overall three times higher, with adjustment for age, race, income, serum cholesterol level, sBP, and reported number of cigarettes/day (P < 0.0001). For men both with and without diabetes, serum cholesterol level, sBP, and cigarette smoking were significant predictors of CVD mortality. For diabetic men with higher values for each risk factor and their combinations, absolute risk of CVD death increased more steeply than for nondiabetic men, so that absolute excess risk for diabetic men was progressively greater than for nondiabetic men with higher risk factor levels. CONCLUSIONS: These findings emphasize the importance of rigorous sustained intervention in people with diabetes to control blood pressure, lower serum cholesterol, and abolish cigarette smoking, and the importance of considering nutritional-hygienic approaches on a mass scale to prevent diabetes. PMID- 8432215 TI - Plasma C3d levels and ischemic heart disease in type II diabetes. AB - OBJECTIVE--To test the hypothesis that the complement system may be activated in patients with type II diabetes and CAD. RESEARCH DESIGN AND METHODS--The plasma C3d concentration was measured in 106 type II diabetic patients and 25 nondiabetic control subjects. The patient group was subdivided according to AER, and the groups were adjusted for age, sex, and known duration of diabetes. For the assignment to a given subgroup, normoalbuminuria was defined as AER < 15 microns/min, microalbuminuria as AER 16-250 micrograms/min, and macroalbuminuria as AER > 250 micrograms/min. The presence or absence of coronary disease was assessed through clinical examination, ECG, and coronary angiography. An RIA system was used for measurement of urinary albumin levels, and the plasma C3d concentrations were measured by ELISA. RESULTS--Within each of the AER-defined subgroups, the plasma C3d levels were significantly higher in patients with IHD than in those without. Thus, in the normoalbuminuric group, plasma C3d levels were 16.3 AU/ml (95% CI 13.9-19) in patients with IHD vs. 11.6 AU/ml (95% CI 10.5 12.7) in those without (P < 0.001). The corresponding data for the microalbuminuric and macroalbuminuric groups were 21.8 (95% CI 18.1-26.3) vs. 13.6 (95% CI 12.3-15.1) and 31.6 (95% CI 24.9-40) vs. 17.5 (13.6-22.6) AU/ml (P < 0.01), respectively. Patients with IHD also had significantly higher plasma C3d levels than normal control subjects, regardless of AER subgroup. A multiple logistic regression analysis demonstrated an association between the plasma C3d concentration and IHD and AER. CONCLUSIONS--Activation of the complement system may play a role in the development of macrovascular disease in type II diabetes. PMID- 8432217 TI - Prevalence of neuropathy in IDDM patients in Piemonte, Italy. The Neuropathy Study Group of the Italian Society for the Study of Diabetes, Piemonte Affiliate. AB - OBJECTIVE: In view of the scarce data available in Italy, to assess the prevalence of neuropathy in various subgroups of IDDM patients living in the Piemonte region of Italy and to develop, based on existing guidelines, and test the practicality of a standardized assessment of diabetic neuropathy. RESEARCH DESIGN AND METHODS: All IDDM patients (766) attending 23 outpatient clinics, evenly distributed in the region, were stratified into 3 age-groups (15-29, 30 44, and 45-59 yr) and into 3 groups of diabetes duration (1-7, 8-14, and > or = 15 yr). A random sample of 467 patients was selected; 81% of whom participated in the studies (196 men and 183 women). The following data were collected: personal and clinical data, structured questionnaire (SQ), neurological examination (NE), vibration sensation (tuning fork) (VS), and two cardiovascular tests (CTs). Patients were classified as follows: stage 0, (no neuropathy) < 2 abnormalities among SQ, NE, VS, and CT; stage 1, (asymptomatic neuropathy) > 1 abnormality among NE, VS, and CT; stage 2, (symptomatic neuropathy) abnormalities in SQ and in NE, and/or VS, and/or CT. RESULTS: The prevalence rates were as follows: stage 0 = 71.5%, stage 1 = 7.2%, and stage 2 = 21.3% and all had a 95% CI. No difference was found between men and women. The prevalence of neuropathy (stages 1 and 2) was higher (P < 0.01) in groups of longer diabetes duration or older age. CONCLUSIONS: Polyneuropathy is a frequent complication in a north Italian IDDM population. Our results suggest that IDDM patients > 30 yr of age, with diabetes of > 15 yr duration, and who complain of symptoms suggestive of neuropathy, should be promptly assessed for the presence of diabetic polyneuropathy. PMID- 8432216 TI - The impact of preconception counseling on pregnancy outcomes. The experience of the Maine Diabetes in Pregnancy Program. AB - OBJECTIVE: To determine if a noncentralized, statewide program could be established to educate health-care providers and women with pregestational diabetes on available strategies to prevent adverse outcomes in pregnancies complicated by diabetes. Characteristics of women who participated in the program and the outcomes of their pregnancies are evaluated. RESEARCH DESIGN AND METHODS: A network of regional providers caring for pregnant women with diabetes was developed. Continuing education sessions were delivered to both providers and women with existing diabetes on the importance of preconception counseling. RESULTS: Maine health-care providers collaborated on the development and adoption of three patient-care guidelines that address preconception counseling, prenatal care, and contraception for women with established diabetes. A total of 185 pregnancies among 160 women with pregestational diabetes reporting estimated delivery dates between 1 January 1987 and 31 December 1990 were identified. Of the total pregnancies, 62 (34%) occurred in women who received preconception counseling: among these 62 pregnancies were one major congenital defect (1.6%) and four fetal or neonatal deaths (6.4%). Among the 123 (66%) pregnancies occurring in women that had not received preconception counseling, 8 (6.5%) infants were born with congenital abnormalities, and 26 (21.1%) fetal or neonatal deaths were documented. CONCLUSIONS: A program promoting preconception counseling can be implemented on a statewide basis by using various health-care providers to deliver the program. Participation in such a program appears to be related to improved pregnancy outcomes among women with pregestational diabetes. PMID- 8432218 TI - Regional cerebral blood flow and cerebrovascular reactivity in IDDM. AB - OBJECTIVE: To investigate both rCBF and cerebrovascular reactivity, evaluated as pre- and post-ACZ rCBF differences in a group of IDDM patients with differences in duration of disease and severity of complications. RESEARCH DESIGN AND METHODS: rCBF was measured by the 133Xenon inhalation method in 20 IDDM patients and in 15 healthy control subjects before and after an intravenous injection of ACZ, a carbonic anhydrase inhibitor commonly used to assess cerebrovascular reactivity. RESULTS: Basal global CBF (the mean of 32 regional values) was within the normal range in all patients but 1, who showed slight hyperperfusion; moreover, in 3 patients with long-lasting disease, some hypoperfused regions were found. ANOVA showed an inverse correlation between basal global CBF (P < 0.01) and duration of diabetes, but no correlation with Hb, MABP, serum glucose concentration, or GHb. Compared with control subjects, the percentage of global CBF increment after ACZ administration was significantly impaired in 4 patients and gave a borderline response in 2 patients; 4 of these poor ACZ responders had retinopathy, and 1 had suffered from a TIA. Duration of diabetes, Hb, MABP, serum glucose concentration, and GHb did not correlate with the percentage of post-ACZ global CBF changes, and did not differ among the 6 poor ACZ responders and the other diabetic patients or control subjects. CONCLUSIONS: These results confirm that global CBF is within the normal range in most IDDM patients, although it is significantly influenced by the duration of diabetes; pathophysiological correlates of the altered cerebrovascular reactivity need to be further investigated. rCBF measurements, before and after ACZ administration, seem to represent a safe and reliable tool for assessing cerebrovascular function in IDDM. PMID- 8432219 TI - Lipoprotein abnormalities in well-treated type II diabetic patients. AB - OBJECTIVE: To investigate lipoprotein levels and composition in well-treated type II diabetic patients. RESEARCH DESIGN AND METHODS: Cholesterol and triglyceride levels were measured in plasma, VLDL, LDL, and HDL in 120 type II diabetic patients in good to fair metabolic control (HbA1c, 7.2 +/- 1.6%) and in 30 normal control subjects. ApoAI, AII, B, CII, CIII, and E levels in plasma were also determined. RESULTS: The diabetic patients have significantly higher levels of mean plasma cholesterol (5.85 vs. 5.43 mM, P = 0.03), LDL triglycerides (0.41 vs. 0.31 mM, P = 0.003), and HDL triglycerides (0.24 vs. 0.19 mM, P = 0.02), whereas total triglycerides, VLDL cholesterol and triglycerides, LDL cholesterol, and HDL cholesterol are not significantly different from normal control subjects. ApoB (150 vs. 135 mg/dl, P = 0.02) and apoCIII (10.6 vs. 8.4 mg/dl, P = 0.01) are significantly higher in diabetic patients compared with control subjects. No significant differences are observed in all the parameters among diabetic patients treated with diet only, sulphonylurea, sulphonylurea plus biguanides, or insulin. Body weight is significantly related to VLDL lipids. The VLDL triglycerides are inversely related to the HDL cholesterol in both diabetic patients and control subjects. The VLDL triglycerides are directly related to the HDL triglycerides only in diabetic patients. No other lipid or lipoprotein parameters are significantly related to body weight or metabolic control. CONCLUSIONS: Type II diabetic patients in good to fair metabolic control are characterized by minor alterations of the plasma lipids, but LDL and HDL triglycerides, apoB, and apoCIII are increased, thus indicating that the lipoprotein composition is altered, possibly because of an abnormal triglyceride metabolism and/or lipid transfer activity. PMID- 8432220 TI - Cerebral and ophthalmic artery hemodynamic responses in diabetes mellitus. AB - OBJECTIVE: To address whether hemodynamic responses in the cerebral arteries and OAs may be altered in patients with diabetic retinopathy. We used TCD to evaluate the effects of changes in BP, posture, and exercise on MCA and OA blood flow velocities. RESEARCH DESIGN AND METHODS: We evaluated 13 patients with BDR, 19 with PDR, and 11 control subjects. Each was tested while supine, breathing 100% oxygen, sitting, and during exercise. RESULTS: Control subjects exhibited linear increases in velocity in the MCA and OA with increases in BP. Those with BDR had higher baseline sBP than control subjects. The MCA velocity response to BP in the BDR group was parallel to, but differed significantly from, the response in control subjects in compensation for the level of BP (ANCOVA F1,53 = 10.1, P = 0.003). The OA velocity response to BP was indistinguishable between the control subjects and the group with BDR. The group with PDR had more elevated BP than control subjects, and those with BDR had more advanced autonomic neuropathy. The PDR group had heterogenous velocity responses in the MCA and OA with respect to BP. None of the control subjects and 3 of 13 of the BDR group had abnormal autoregulatory velocity responses in the MCA or OA to 100% oxygen breathing, whereas 12 of 19 PDR patients were abnormal (P < 0.01). Of those with PDR, 4 had elevated MCA and 3 had elevated OA velocities while supine at rest. CONCLUSIONS: Patients with PDR demonstrated abnormal hemodynamic responses of the cerebral and ophthalmic circulation both at rest and with exercise. PMID- 8432222 TI - Proposed strategies for reducing user error in capillary blood glucose monitoring. The National Steering Committee for Quality Assurance in Capillary Blood Glucose Monitoring. AB - For individuals with diabetes mellitus, CBGM provides a more accurate picture of daily glucose fluctuation than urine glucose testing (1-9). As a result, CBGM is the preferred method to assess short-term glucose control and provide data for management decisions and insulin adjustment (10-16). Moreover, the wide availability of glucose monitoring systems designed for patient use has made SMBG the standard of care in diabetes management for all capable persons with insulin requiring diabetes and an appropriate management tool for persons with non insulin-requiring diabetes (13-20). In spite of the relative accuracy of current CBGM systems in measuring blood glucose levels, a recent study by the FDA suggests that user-procedural errors can cause inaccurate results (21). Inaccurate data affect patients efforts to achieve good metabolic control and, if used as the basis for regimen adjustment, may endanger health (21-42). Therefore, until reliable, technique-free systems are available, the accuracy of data with this technology must be improved through reduction of user error. This article presents strategies to accomplish this goal recommended by a national group of experts, the NSCQA in CBGM. PMID- 8432221 TI - Long-term effects of protein-restricted diet on albuminuria and renal function in IDDM patients without clinical nephropathy and hypertension. AB - OBJECTIVE: To determine the long-term effects of an LPD on albuminuria and renal hemodynamics in IDDM patients without nephropathy. RESEARCH DESIGN AND METHODS: We selected 31 patients with overnight albuminuria between 10 and 200 g/min and without hypertension from a referral-based diabetic clinic. One participant dropped out. A 2-yr randomized prospective study was conducted on 14 patients assigned to an LPD (0.6 g.kg-1.day-1) and 16 patients assigned to continue their UPD. Protein intake was assessed by using urinary urea excretion. Albuminuria (three overnight collections) was measured at baseline and on seven occasions thereafter. GFR and ERPF were measured annually using [125I]iothalamate and [131I]hippuran, respectively. RESULTS: In the LPD group, protein intake decreased from 1.05 +/- 0.32 to 0.79 +/- 0.16 g.kg-1.day-1 (P < 0.005), but only seven participants consumed < 0.8 g.kg-1.day-1. Protein intake was unaltered in the UPD group (P < 0.001 vs. LPD). Baseline albuminuria and renal hemodynamics were not different in the groups. In the LPD group albuminuria decreased from 36 (95% CI, 16-83) to 30 micrograms/min (95% CI, 14-67) (P < 0.05). After adjustment for MAP and diabetes duration, the decrease in albuminuria in the LPD group was 26% (95% CI, 13-36) (P < 0.001), which was significantly different from the 5% (95% CI, 10-22) change in the UPD group (P < 0.005 vs. LPD). Multiple regression analysis showed the actual decrease in protein intake lessened (P < 0.005), whereas prevailing MAP accelerated albuminuria (P < 0.001). Low-protein intake independently reduced ERPF (P = 0.009) and GFR (indirectly via ERPF, P < 0.001) after 1 yr. Only minor changes in renal hemodynamics occurred in the second yr. CONCLUSIONS: This study suggests that long-term dietary protein restriction beneficially reduces albuminuria and renal hemodynamics in IDDM patients with mildly elevated albuminuria. Systemic BP counteracts these effects even in the absence of hypertension. Suboptimal compliance limits diet efficacy. PMID- 8432224 TI - Influencing the attitudes of medical students toward diabetes. Results of a controlled study. AB - OBJECTIVE: To determine the effect of two educational interventions on the diabetes-related attitudes of medical students. RESEARCH DESIGN AND METHODS: We studied 67 junior and senior medical students who were participating in the University of Michigan Medical School's Family Practice elective clerkship. Students were assigned to one of two interventions. The first was a 1-wk living with-diabetes behavioral simulation that involved injections, blood glucose monitoring, diet, exercise, and record keeping. The second intervention involved reading an autobiography about living with diabetes and viewing a videotape about the psychosocial impact of diabetes. RESULTS: No differential impact was found between the two interventions. However, both interventions were followed by a modest positive change in the attitudes of the medical students (which were very positive to begin with) toward the importance of patient autonomy and the value of the team approach to diabetes care. The attitude gains persisted at follow-up for patient autonomy but returned to baseline for team care. CONCLUSIONS: This study suggests that these two educational interventions resulted in modest increases in the already positive attitudes of medical students toward the importance of patient autonomy and team care in diabetes. However, because the study did not include a group that received no treatment, we cannot be certain on this point. The attitude gain related to team care did not persist at follow-up. These findings are consistent with classical attitude research, which suggests that attitudes are sensitive to influences such as these interventions, but that attitude changes may not persist when those influences are changed or withdrawn. We were not able to find a differential impact between the two interventions and suspect that the general nature of the DAS used as the dependent measure may not have been sensitive enough to capture such a differential impact. PMID- 8432223 TI - Low-dose acarbose improves glycemic control in NIDDM patients without changes in insulin sensitivity. AB - OBJECTIVE: To examine the impact on metabolic control in NIDDM patients of the alpha-glucosidase inhibitor, acarbose, when administered at a low dose in powdered form. RESEARCH DESIGN AND METHODS: Six subjects were recruited for a double-blind cross-over trial using 25 mg powdered acarbose and a placebo 3 times a day with meals for 3 mo. In addition to parameters of diabetes control and body weight, glucose turnover and insulin sensitivity were measured with the hyperinsulinemic/euglycemic clamp technique combined with tracer kinetics. RESULTS: None of the subjects showed significant changes in FPG levels or body weight either on the 3-mo course of acarbose or placebo. HbA1c fell significantly from 10.6 +/- 1.0 to 9.4 +/- 1.3% (P = 0.05) during treatment with acarbose but failed to change on placebo (10.1 +/- 1.0 to 11.1 +/- 2.0%; P = 0.36). Basal HGP and glucose utilization were unchanged during either of the treatment periods, and hyperinsulinemia produced a similar degree of suppression of HGP before and after each treatment. At a physiological concentration, insulin failed to stimulate glucose clearance in these diabetic patients, and no improvement was seen with acarbose treatment. No changes in plasma lipids or lipoprotein profiles were demonstrated after 3 mo on acarbose. In acute studies, it was shown that administration of acarbose at a dose of 25 mg powder per meal significantly decreased the postprandial glycemic excursion. CONCLUSIONS: When administered in the powdered form at the low dose of 25 mg 3 times/day with meals over 3 mo, acarbose was well tolerated by the NIDDM patients and was without side effects. It improved glycemic control by reducing postprandial hyperglycemia, but had no effect on glucose turnover, insulin sensitivity, or lipid profile. PMID- 8432225 TI - Patients' attitudes toward screening for gestational diabetes mellitus in the Illawarra area, Australia. AB - OBJECTIVE: To examine the attitudes toward screening of a group of women who have had GDM compared with a group who were screened but did not have GDM. RESEARCH DESIGN AND METHODS: We surveyed 90 women with GDM and 100 control women with a postal questionnaire. They were asked to mark on a six-point Likert scale their responses to statements about certain aspects of screening for diabetes in pregnancy. RESULTS: No significant differences were found in mean responses between the two groups. The method of screening was found to be convenient (GDM group, 5.02; control group, 4.77). A strong belief that all women should be screened in pregnancy (GDM group, 5.76; control group, 5.66) and a personal desire for screening in any future pregnancy (GDM group, 5.73; control group, 5.62) were expressed. CONCLUSIONS: Both groups of women surveyed in this study were extremely positive about the convenience of the screening method used, the need for all women to be screened in pregnancy, and their desire for screening in future pregnancies. PMID- 8432226 TI - Designing medical and educational intervention studies. A review of some alternatives to conventional randomized controlled trials. AB - The advantages and limitations of RCT designs are discussed, and a range of alternative designs for medical and educational intervention studies considered. Designs selected are those that address the much neglected psychological issues involved in the recruitment of patients and allocation of patients to treatments within trials. Designs include Zelen's (18) randomized consent design, Brewin and Bradley's (20) partially randomized patient-centered design, and Korn and Baumrind's (21) partially randomized clinician-centered design. The possibilities of combining features from each of the last two designs are illustrated, and the advantages of adopting a more flexible and clinically relevant approach to the design of clinical trials are discussed. PMID- 8432227 TI - Perceived symptoms in the recognition of hypoglycemia. AB - For people with diabetes, detection of hypoglycemic symptoms is a critical tool for the recognition and treatment of hypoglycemia. This is not a simple process involving only the occurrence of a hypoglycemic-relevant physiological event, such as sweating. We propose a four-step biological and psychological model that leads to the accurate recognition of hypoglycemia through symptoms. The model illustrates both the chronic and transient modifiers that can enhance and interfere with recognition of hypoglycemia. Three common methods are used to investigate the occurrence and utility of hypoglycemic symptoms that relate to this model. This article reviews the advantages and disadvantages of these methods, providing previously unpublished illustrative data. The field study hit/false alarm approach was shown to be the most useful method. The relevance of this model and data to the concept of hypoglycemic awareness/unawareness and blood glucose awareness training is discussed. PMID- 8432228 TI - Counting diabetes in the next millennium. Application of capture-recapture technology. AB - Monitoring diabetes is critical for our understanding of the etiology and natural history of disease and for public health actions. However, traditional methods for monitoring are either too expensive (e.g., IDDM registries, NIDDM-OGTT prevalence surveys) or too inaccurate (routinely collected data or passive surveillance) for broad accurate, national programs for monitoring the incidence and prevalence of disease. We suggest that one technology called capture recapture would considerably increase our ability to "count" diabetes, both nationally and globally. Implementation of this approach could lead to accurate inter- and intracountry data on rates of disease. Moreover, such tracking of diabetes could serve as the model for the monitoring of all disease in the 21st century and beyond. PMID- 8432229 TI - In vivo glucose monitoring: sense and sensorbility. PMID- 8432230 TI - Diabetes and hypertension: not the final chapter. PMID- 8432231 TI - [The programming of the pulse amplitude: the effect on the longevity of cardiac pacemakers with high and low inhibition currents]. AB - Recently developed rate-responsive cardiac pacemakers are smaller than conventional ones because of their smaller battery capacity. The influence of programming pulse amplitude on battery current was investigated in 13 patients (six women, seven men; mean age 66 +/- 11 years), seven with a small pacemaker (1.2 Ah battery capacity) and six with a conventional model (1.65 Ah battery capacity), 3-12 months after pacemaker implantation. The telemetrically measured battery current of the conventional pacemaker was significantly greater than that of the smaller one. While stimulation currents were the same, the conventional model had a higher inhibition current (22 +/- 0 microA) than the rate-responsive one (7.1 +/- 0.1 microA). At 5 V impulse amplitude the calculated period of functioning was 5.8 years for the conventional pacemaker and 8.2 years for the rate-responsive one. Programming for 2.5 V increased the calculated period of functioning by 1.5 for the conventional and by 5.1 years for the rate-responsive pacemaker. The smaller, rate-responsive pacemaker thus has a longer period of functioning, at least 7 years, because of its superior circuitry. By programming the impulse amplitude at 2.5 V the period is increased to more than 10 years. PMID- 8432232 TI - [Pulsatile insulin secretion into the portal vein in liver cirrhosis]. AB - To characterize the pulsatile liberation of pancreatic hormones, blood was taken from the portal vein of four patients (three men, one woman; aged 65-71 years) with alcoholic (n = 3) or posthepatitic (n = 1) liver cirrhosis. The concentrations of glucose, insulin, C-peptide and glucagon were measured within one minute. The concentrations of insulin, C-peptide and glucagon varied considerably in intervals of 4.1-6.5 min. The swings in insulin concentration ranged between 17 and 163.5 microU/ml. Oral glucose loading with 100 g increased the insulin and C-peptide swings, but not their periodicity. This indicates that pulsatile insulin secretion is amplitude not rate driven. PMID- 8432233 TI - [Nontuberculous mycobacteriosis as a complication of the Swyer-James syndrome]. AB - The chest radiograph of a 35-year-old man with fatigue, exertional dyspnoea and haemoptyses revealed a cavity in the left upper lobe and a shrunken left lung with radiolucency greater than that on the right. Acid-fast rods in sputum were identified as Mycobacterium kansasii on culture. Scintigraphy showed a 9% residual perfusion on the left and abnormal ventilation, compatible with Swyer James syndrome. This had favoured the development of a mycobacterial infection. There was also a decrease in ciliary function (rate of 4-7 Hz, normal: 10-11). Treatment, begun when tuberculosis had been suspected, was after sensitivity tests changed to a combination of rifampicin (600 mg), ethambutol (1600 mg) and protionamide (500 mg) daily. There was marked regression of the findings within 4 weeks, but treatment was prematurely stopped after 11 months. Two years later there was a recurrence which again responded well to the same drug regimen with additional sulphamethoxazole (1600 mg/d). PMID- 8432234 TI - [Foreign body aspiration]. PMID- 8432235 TI - [Bleeding from the small and large intestines. Its radiological diagnosis and therapy]. PMID- 8432236 TI - [The observations and reflections of a pharmacologist]. PMID- 8432237 TI - [Oral anticoagulation]. PMID- 8432238 TI - [The HBs antigen in asymptomatic chronic hepatitis B]. PMID- 8432239 TI - [Polymyalgia rheumatica and influenza vaccination]. PMID- 8432240 TI - [Human insulin and severe hypoglycemias]. PMID- 8432241 TI - [Table salt and blood pressure]. PMID- 8432242 TI - Prehospital care. AB - To improve patient outcome and reduce time at the scene, treatment protocols for specific injuries and rapid transport should be established with individual systems. These standards should be based on such parameters as history, mechanism of injury, physiologic status of the patient on arrival, triage criteria, and predicted transport times. Ensuring airway patency and stability is a vital function that must be rapidly and carefully performed. Any patient at risk for neck or back trauma needs to be immobilized quickly using a rigid cervical collar with head immobilizer and long backboard. Initiation of IV fluids is acceptable if this skill can be accomplished within several minutes and does not significantly postpone transport. When prolonged or delayed transport times are encountered, aeromedical evacuation should be considered. Medical direction by a qualified physician with an interest in prehospital care and emergency medical services is an essential component in any successful system. The medical director should be strategically involved with protocol development, training and continuing education, and continuous quality improvement. Intensive supervised training in trauma management for EMTs and paramedics will help to reduce the amount of time spent at the scene of an accident. Emergency medical services have certainly come a long way over the past century. Indeed, more research is necessary in order to confirm, perfect, or dispute the many traditional theories that have been a part of prehospital technology. As the field of emergency medicine continues to develop and expand, so too will the specialty of prehospital medicine. Napoleon would be proud! PMID- 8432243 TI - Blunt abdominal trauma. AB - The management of the patient with blunt abdominal trauma remains in continuous flux. The emergency physician cannot place undue reliance on physical examination, and plain radiography of the abdomen rarely adds to patient care. Laboratory tests, particularly elevated liver function tests or a large base deficit, may increase our suspicion for intraabdominal trauma. However, normal blood tests should never prevent further investigation as warranted by mechanism of injury or clinical picture. Ultrasound and laparoscopy are two diagnostic interventions that have been more extensively studied abroad than in the United States. With the advent of large clinical trials in our own country they should play a growing role in the diagnosis and management of abdominal trauma in the coming decade. DPL revolutionized the diagnosis of intraabdominal injury. It has an astoundingly impressive track record of 97% accuracy that is rivaled by few other tests in medicine. It has been criticized at times for being overly sensitive to trivial injuries, leading to nontherapeutic laparotomies. CT has the advantage of being relatively noninvasive and theoretically has the potential for decreasing nontherapeutic laparotomies, but is very reader-dependent and in many studies not as sensitive as peritoneal lavage. Both CT and DPL may miss critical intraabdominal injuries, but this is much less likely with lavage. Perhaps the greatest risk of CT is the delay it adds to performing a needed laparotomy. CT provides an excellent modality to screen for abdominal injury in the stable patient. However, the more critically injured a patient is, the greater the danger of delays introduced by CT. In these patients, greater emphasis should be placed on immediate DPL or direct transport to the operating room. The challenge in the 1990s will be to refine the diagnosis of intraabdominal trauma to allow for swift recognition of those injuries that require surgical intervention. PMID- 8432244 TI - Penetrating abdominal trauma. AB - Penetrating trauma of the abdomen no longer warrants automatic laparotomy. Reasonably accurate clinical predictors of the need for operation should first be employed. Patients who do not meet these clinical criteria undergo a selective diagnostic approach on the basis of mechanism and site of injury and the experience and expertise of the respective institution. The desire to avoid unnecessary laparotomy is laudable. Nevertheless marked morbidity or mortality caused by failure to conduct laparotomy in a timely manner can be a dreaded consequence. When clinical and diagnostic studies are unable to resolve the presence or severity of injury, laparotomy is often more prudent than expectant observation. PMID- 8432245 TI - Genitourinary trauma. AB - Evaluation of genitourinary trauma can be confusing. This article discusses identifying the significant injuries, those patients at risk for developing these injuries, and the radiographic procedures that will effectively stage these injuries so that appropriate management can be proposed. PMID- 8432246 TI - Pelvic fractures. AB - Extensive knowledge of pelvic fractures is a must for emergency physicians. The emergency physician must be able to distinguish the minor fracture from one that is more severe, one that may have associated injuries, and one that is quite possibly life threatening. PMID- 8432247 TI - Scoring systems and triage from the field. AB - No single system exists that will guarantee triage success. Familiarity with anatomic and physiologic indicators along with an awareness of the significance of injury mechanism and existing comorbid factors is mandatory for all who participate in trauma care. Moreover, there are unique demands of the prehospital environment. Until further refinements are made, a prehospital trauma triage system should minimize undertriage and its unnecessary morbidity and mortality. PMID- 8432248 TI - Head trauma. AB - An estimated 60,000 patients with severe head injury reach the Emergency Department alive each year; 50% of these patients have significant elevations in intracranial pressure at or shortly after arrival. Aggressive emergency department management with particular attention to airway management, control of intracranial pressure, and proper use of radiographic studies is crucial to successful neurologic recovery. PMID- 8432249 TI - Pediatric trauma. AB - Injured children require an organized, properly equipped, team approach to management. The emergency physician must be aware of the anatomic and physiologic differences that predispose the child to certain injuries. Aggressive airway and hemodynamic resuscitation are essential in the critically injured child. A network of pediatric trauma consultants should be identified in your region for early consultation and referral. Continued research and the ongoing epidemiologic studies from the National Pediatric Trauma Registry will improve our understanding and management of the injured child. It is essential for each of us to become a strong injury prevention advocate in our own community. PMID- 8432250 TI - Trauma in pregnancy, what if ...? AB - Pregnancy produces unique physical and physiologic changes. These changes alter, sometimes significantly, the presentation of trauma pathology. This article examines some of the unusual findings and controversies surrounding injury during pregnancy. PMID- 8432251 TI - Alcohol and trauma. AB - Alcohol usage is an integral causal factor in all types of trauma. Additionally, both the acute and to a much greater extent chronic usage of alcohol impair the body's normal physiologic responses to injury. Emergency physicians are painfully aware of the relationship between alcohol and trauma. However, we occasionally fail to appreciate the body's altered response and physical state due to alcohol. We frequently fail to use this opportunity to confront patients with the fact that they have a problem and refer them appropriately to rehabilitation programs. PMID- 8432252 TI - The cost of injury. AB - The public health problem of injury has an enormous impact on individuals and society, both as a health and economic issue. Prior to the last decade, little attention has been paid to the costs generated by injury, much of which is preventable. By looking at aggregate economic costs for different injuries and population groups, the physician can understand where the problems occur that need to be addressed to curb this staggering burden on society. PMID- 8432253 TI - Injury control. A crucial aspect of emergency medicine. AB - We have briefly described the theoretic and strategic concepts of injury control and suggested ways for emergency medicine to be more broadly involved. It is not enough for emergency physicians to be active solely in the acute management of injured patients. Emergency physicians need to "look upstream" and balance their focus on the acute management of injuries with a focus on the prevention of injuries. PMID- 8432254 TI - Management of multiple trauma. AB - Multiple trauma management requires organization, teamwork, and rapid clinical intervention. The physician in both the trauma center and the community hospital should have a system for evaluation, treatment, and referral. Certain patients may have uncharacteristic responses to shock and stress, and one must be prepared to re-evaluate treatment plans. Finally, caring for trauma victims also includes knowledge of organ donation and survivor death counseling. PMID- 8432255 TI - Airway management. AB - The approach to airway management in the multiple trauma patient has changed significantly over the past decade. A number of central controversies have been identified, and the debates continue. This article identifies the major controversies in trauma airway management, reviews and summarizes relevant literature, and presents specific recommendations and supporting arguments. Particular emphasis is placed upon the role of endotracheal intubation, use of neuromuscular blocking agents, and the issue of neuromuscular blockade versus rapid tranquilization of the combative trauma patient. PMID- 8432256 TI - Prehospital fluid resuscitation of the trauma patient. An update on the controversies. AB - The most efficacious means of prehospital volume resuscitation of the trauma patient has been debated for many years; more recent discussion has questioned the indications for any prehospital resuscitation. This article reviews the various viewpoints active in each of these areas, summarizes the current status of the disputed issues, and offers suggested directions for further research. PMID- 8432257 TI - Blunt neck injury. AB - Emergency physicians must diagnose or exclude cervical spine trauma in daily practice. This is a complicated task, as the presentation may be subtle and the manifestations obscured, and no imaging modality is completely sensitive or specific. The research of the past two decades serves as a guide as to which types of patients require cervical radiologic evaluation and which modalities of evaluation are appropriate. PMID- 8432258 TI - Blunt chest trauma. AB - The spectrum of injuries after blunt chest trauma presents a challenging problem to the emergency physician. The clinician must select among a number of diagnostic tests and therapeutic options after the initial history and physical examination has been performed. Nine clinical entities are discussed: sternal fracture, flail chest, pulmonary contusion, tracheobronchial injuries, myocardial contusion, myocardial rupture, aortic disruption, esophageal perforation, and diaphragm rupture. Emphasis is placed on newer diagnostic modalities available for these conditions. PMID- 8432259 TI - Penetrating chest trauma. AB - Penetrating chest trauma causes a broad spectrum of injury that requires a variety of diagnostic and resuscitative skills. Prompt resuscitation and decisive action are mandatory for patients who present in extremis, whereas a thorough diagnostic evaluation and appropriate observation are indicated in less compelling circumstances. Clinical skill and judgment along with plain radiographs provide the basis for treatment in most cases. More sophisticated imaging techniques, with the exception of angiography, are of limited value. A systematic approach based on wound location, be it central, peripheral, or proximate to the diaphragm, should result in timely resuscitation and sound diagnostic evaluation. PMID- 8432260 TI - Risk factors for lung cancer among nonsmoking Illinois residents. AB - The purpose of this study was to examine possible risk factors for lung cancer among nonsmokers. The Illinois State Cancer Registry was used to identify all nonsmoking lung cancer cases diagnosed between 1985 and 1987. Subjects were classified as nonsmokers only if their medical record specifically stated that they had never smoked during their lifetime. These cases were compared with nonsmoking colon cancer cases. White male nonsmoking lung cancer cases were more likely to have worked in the construction industry than controls [odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.2-2.3] and to have worked in the bus service and urban transit industry (OR = 2.6, 95% CI = 1.0-6.9), in the trucking service industry (OR = 2.1, 95% CI = 1.3-3.6), and in blast furnaces, steelworks, and rolling and finishing mills (OR = 1.9, 95% CI = 1.0-3.6). White female cases were more likely to have worked as registered nurses than were the controls (OR = 1.9, 95% CI = 1.0-3.5). Negative associations between lung cancer and farming were found in both white males (OR = 0.6, 95% CI = 0.5-0.7) and white females (OR = 0.1, 95% CI = 0.01-0.6). Several other less plausible associations between employment and lung cancer were also found. To determine whether urban residence and associated air pollution increased the risk of lung cancer for nonsmokers, rates among nonsmokers in Cook County were compared with those in the remainder of Illinois. Cook County rates of nonsmoking lung cancer were elevated among white females and nonwhite females, but not among males. Residences of the white female and nonwhite female lung cancer cases were mapped to determine whether clustering within Chicago had occurred. The absence of observable clustering suggests that the excess of female lung cancer cases in Cook County is not attributable to pollution. PMID- 8432261 TI - Factors influencing the assessment and control of occupational hazards in developing countries. AB - The principles of occupational health may be the same in the developed and developing countries. However, there can be a wide diversity in practice. The exposure to chemicals at the workplace in developing countries is usually of a different nature, and the level of exposure is generally of a higher magnitude. The leading occupational diseases in developing countries are also very different to those reported in industrialized nations. For hazard evaluation in developing countries, more factors need to be considered. Problems are usually more complicated as most workplaces are subjected to many factors which typify small scale industries. Low capital investment often culminates in cutbacks on necessary expenses, especially on occupational or environmental health activities. Thus the health, safety, and welfare of the workers are usually overlooked. This situation helps only to promote greater risks to the workers. Furthermore, many workers in the developing countries suffer from poor nutrition, endemic diseases, and other debilitating conditions. For these reasons, it is possible that currently recommended occupational exposure limits could allow injury to workers in the developing nations. When carrying out health assessment, careful attention must be paid to cultural practices, genetic components, working conditions, and other predisposing factors. This paper reviews some of the current techniques commonly used for the monitoring of toxic substances and an in depth discussion on various problems facing the developing countries concerning the usage of these techniques. PMID- 8432262 TI - Studies on production of anticollagen antibodies in silicosis. AB - Silicosis is characterized by pulmonary fibrotic changes which consist primarily of an increase in collagen. In this study, anticollagen antibodies in the serum of 134 silicosis patients versus 40 normal subjects were examined and their relationship with immunoglobulin, autoantibodies, and procollagen III peptide (PIIIP) was investigated by enzyme-linked immunosorbent assay (ELISA). The mean levels of anti-human type I collagen (HI) and anti-human type III collagen (HIII) antibodies were significantly higher in the silicosis patients versus the normal subjects (P < 0.001). However, no differences were observed in the mean levels of anti-human type IV collagen (HIV) antibodies in the silicosis patients versus the normal subjects. Anticollagen antibodies in the sera of silicosis patients appear to be formed at an early stage of the disease. We observed a correlation between anticollagen antibodies and immunoglobulin. There was a tendency toward high values of anticollagen antibodies in the sera of patients positive for antinuclear antibodies (ANA) and rheumatoid factor (RF), both of which are autoantibodies. However, no correlation was observed between serum PIIIP and anticollagen antibodies. These observations suggest that, in silicosis, there is a relationship between anticollagen antibodies and immunoglobulins, as well as between anticollagen antibodies and autoantibodies. Measurement of anticollagen antibodies in the sera of silicosis patients offers a useful index for evaluating the prognosis of pulmonary fibrosis and autoimmune abnormality in silicosis. PMID- 8432263 TI - Neuropsychological effects of chronic exposure to environmental dioxins and furans. AB - The environmental contamination by dioxins and furans (PCDD/PCDF) of a local area in southwest Germany due to pyrolytic processes led to a survey of health consequences in the exposed population. 2,3,7,8-TCDD (8000 ng/kg TE (ppt)) was found in the soil and up to 585000 ng/kg TE in attic dust in private homes. In a randomized study group of definitively exposed persons, a neuropsychological test battery was applied and its value as a diagnostic tool investigated. A total group of 19 persons participated in a standard neuropsychological examination including common procedures to evaluate mnestic and attentional performance and psychomotor speed (e.g., WAIS, WMS-R, TMT, and symptom and mood checklists). The range of PCDD/PCDF between 16 and 80 (mean 31) ppt did not vary substantially from blood fat values in a national sample. Results of neuropsychological testing showed only slight deviations from the expected range. Nevertheless, in a high level exposure group, a reduction of verbal conceptualization, mnestic organization of verbal and visual stimuli, and psychomotor slowing was found. Among other correlations visual exploration speed (TMT) was most directly related to TE. Affective symptoms (such as irritability and emotional instability) were also related to exposure. Results indicate that standard neuropsychological testing can be recommended for the routine evaluation of chronic dioxin exposure. PMID- 8432264 TI - Relationship between subjective sleep rating and objective sleep parameters: a case study. AB - The subjective sleep of a male subject was related to 22 objective polygraphic sleep parameters on 39 experimental nights. Subjective sleep was rated by the sleeper himself as "good," "moderate," or "poor" upon arising, for 10, 24, and 5 nights, respectively. Differences in the 22 sleep parameters for these three ratings were examined, and poor sleep showed a significant increase in stage W (waking), an elongation of sleep latency, a decrease in mean sleep depth during the night and 2 hr after going to bed, a decrease in integrated value of sleep depth during the night, an increase in the gradient and decrease in the intercept of regression line of sleep depth against time, and a shortening of total sleep time. The average delta wave percentage per epoch was greater for a subjective rating of "moderate" than for the other groups. Canonical discriminant analysis was conducted using 16 sleep parameters, and the overall correct identification rate of three subjective sleep ratings by the objective sleep parameters was 89.7%. Variables of the first or second axis with large standard coefficients were stages 1, 2, REM (rapid eye movement), integrated voltage of electromyogram, and sleep latency. From the above two sets of analyses, sleep latency was the most useful parameter for predicting subjective sleep. PMID- 8432265 TI - Vibrotactile threshold testing in occupational health: a review of current issues and limitations. AB - Quantitative cutaneous vibrotactile threshold measurement has been proposed as a useful method for assessing peripheral nervous system function in occupational and environmental neuroepidemiology. It allows rapid, quantitative, and nonaversive assessment of peripheral nervous system function. Acceptance of this method is currently limited, however, because of poor standardization of methods, the lack of data regarding the effects of age, gender, and other covariates, and minimal demonstration of association between vibrotactile threshold and conventional measures of peripheral nerve function. Data from a series of validation studies intended to address some of these problems are presented and relevant literature is discussed. Specifically, results of studies in which reliability and time efficiency of testing protocols were measured, the effects of covariates on measurement of vibrotactile threshold were estimated, and vibrotactile thresholds were compared to physical examination and electrophysiologic evaluation are discussed. Recommendations are made regarding choice and standardization of testing protocol, covariates, and issues for future research. PMID- 8432266 TI - Synergic lung changes in rats receiving combined exposure to paraquat and ionizing radiation. AB - Experiment was carried out on a total of 160 male Wistar rats. Paraquat was instilled per os intragastrically by a metal probe, in aqueous solution, at a daily dose of 0.46 mg/kg body wt given five times a week for 4 months. Directly upon termination of paraquat intake the animals received a single external whole body exposure to 4 Gy of ionizing radiation. Changes in the parameters studied were recorded on Post-treatment Days 1, 5, 10, and 30. In bronchoalveolar lavage fluid (BALF), paraquat treatment alone was found to elevate lactate dehydrogenase (LDH) activity and content of thiobarbituric acid (TBA) reactants; lung homogenate from this treatment group showed diminution in superoxide dismutase (SOD) and catalase (CAT) activities and in content of nonprotein sulfhydryl groups (NPSH) on Days 1 and 5. Irradiation alone produced less substantial changes. With combined exposure to paraquat and radiation, there was more marked and more prolonged depression of the three parameters (SOD, CAT, and NPSH) of lung antioxidant defense and synergic increase in BALF content of TBA reactants and LDH activity. PMID- 8432267 TI - The use of behavioral and psychophysiological methods in the monitoring of health at the worksite. AB - The paper discusses the possibility of identifying and preventing certain occupational health hazards by assessing and evaluating a number of behavioral and psychophysiological responses induced by exposure to unfavorable environmental conditions at work. The main aspects of the research strategies and measurement methods used in this field of research are described to provide a background for the establishment of a policy of health promotion based on the monitoring of early behavioral and psychophysiological indices of functional CNS changes at the worksite. PMID- 8432268 TI - Neurotoxic syndromes and occupational exposure to solvents. AB - Neurotoxic syndromes due to occupational solvent exposure present a worldwide health problem, the magnitude of which varies from country to country. Apart from the relatively clear-cut exposure-effect relationships in acute solvent intoxications, those caused by long-term, low-level occupational exposure to solvents are more difficult to detect. Controversial opinions and even debate are frequently encountered in literature on this matter. This is partly due to differences in neurobehavioral methods used, partly to difficulties in obtaining accurate information about exposure. These effects can be studied in humans using biochemical, clinical, and epidemiological methods. It is thus quite conceivable that direct comparison of the results obtained by different methods is not always possible. Moreover, exposure to a variable mixture of solvents is frequent in an occupational setting which is problematic from the toxicological point of view. The clinical pictures of "chronic" occupational solvent intoxications are, with few exceptions, quite nonspecific in nature and share several common features regardless of the underlying chemical exposure. The development of manifest disease is insidious and high interindividual variation of symptoms and signs exists. Some solvents cause primarily peripheral neuropathy. Deterioration in many psychological and neurophysiological functions can be seen. The most common subjective symptoms of solvent intoxication are headache, tiredness, memory disturbances, and dizziness. Clinical findings comprise signs of the central nervous system depression (psychoorganic syndrome, tiredness), dizziness, disturbances in coordination, and general neurasthenic signs. From the clinical point of view, it is important to define the criteria for a diagnosis. In different countries the diagnostic criteria for solvent intoxication may vary considerably, which provides additional difficulties in interpreting the results of studies in this field. PMID- 8432269 TI - Suxamethonium and atracurium: sequential and simultaneous administration. AB - The interaction between suxamethonium and atracurium was investigated during anaesthesia with thiopentone, fentanyl, enflurane and nitrous oxide in oxygen with controlled ventilation. Electromyographic data (Relaxograph, Datex) from 30 patients in three, equal groups were analyzed. Group 1 received atracurium 0.23 mg kg-1. Group 2 received suxamethonium 1 mg kg-1 followed by atracurium 0.23 mg kg-1 when the EMG had recovered to 20% of its control value: a sequence intended to be representative of clinical practice. Group 3 received suxamethonium 1 mg kg 1 and atracurium 0.23 mg kg-1 in rapid succession. Plasma cholinesterase concentrations and Dibucaine and fluoride numbers were within normal limits in all patients. Suxamethonium given for endotracheal intubation (group 2) neither potentiated the subsequent atracurium blockade nor delayed spontaneous recovery. When suxamethonium and atracurium were given in rapid succession (group 3), the duration of suxamethonium blockade was reduced considerably but the recovery from the atracurium component of the blockade was not significantly different from groups 1 and 2. Although the intubation score at 60s was no worse in group 3, the duration of profound blockade suitable for intubation was reduced to such an extent that the simultaneous administration of suxamethonium and atracurium cannot be recommended in clinical practice when there is a requirement for rapid endotracheal intubation. PMID- 8432270 TI - A training simulator for detecting equipment failure in the anaesthetic machine. AB - Simulation is often used for training personnel in activities where the consequences of inappropriate actions are serious. We report a realistic training simulator, which can reproduce practically all potential malfunctions in the anaesthetic machine. Using actual standard equipment (Dameca 10750), the interior of the anaesthetic machine has been profoundly modified, whereas the external appearance remains virtually unchanged. The concealed alterations allow 20 different pre-set technical faults to be activated selectively from a mobile control unit. While assisted by an instructor, the trainee performs hands-on interactive experimentation with the simulator, while being exposed to 'unexpected' machine faults, which prompt for interpretation of error symptoms. Alternatively, the trainee can personally activate the simulated symptoms of different component failures, to enhance learning of the functional principles of the apparatus. The latter approach also allows a systematic presentation of defects to be identified by each step in a formal safety checklist for anaesthetic machines. PMID- 8432271 TI - Anaesthesia and radiofrequency endometrial ablation. AB - Radiofrequency endometrial ablation is a new technique for the treatment of functional menorrhagia. A conductive probe is placed in the uterine cavity which selectively destroys the endometrium by heating, using radiofrequency energy. Hence the patient is charged with a high density electric field. ECG electrodes need to be applied with care and patient-metal contact must be avoided to prevent radiofrequency burns. Monitors may require additional filters. PMID- 8432272 TI - French obstetric anaesthetists and acid aspiration prophylaxis. AB - In 1988, a confidential postal questionnaire was prepared in order to assess the techniques used routinely in France for prophylaxis of aspiration of gastric contents in obstetrics. Of the 297 anaesthetists who responded, 81% (237) worked almost always and 19% worked occasionally in obstetric anaesthesia. Although obstetric anaesthesia is considered to carry a particular risk of aspiration of gastric contents (88.5% of responders), only 23% used in every case a complete set of prophylactic measures. The use of antacids has recently increased in France. Particulate antacids are no longer used whereas sodium citrate, cimetidine and ranitidine are prescribed by about 30%, 50% and 15% respectively of practitioners. Among the users of cricoid pressure, 52% were able to describe precisely the technique. Tracheal intubation is considered mandatory when general anaesthesia is performed for Caesarean section but not for uterine revision or instrumental manoeuvre. 74% of obstetric anaesthetists believe that regional anaesthesia is the best anaesthetic technique for Caesarean section. This survey has shown both positive results indicating that continuing medical education of French anaesthetists follows at least in part the 'state of the art' and insufficiencies indicating that training continues to be necessary to reduce the mortality related to aspiration of gastric contents. PMID- 8432273 TI - Blindness following bilateral neck dissection. PMID- 8432274 TI - Delayed asystole during spinal anaesthesia for transurethral resection of the prostate. PMID- 8432275 TI - Intubation with propofol: evaluation of pre-treatment with alfentanil or lignocaine. AB - The effect of lignocaine or alfentanil pre-treatment on conditions at orotracheal intubation following induction with propofol, but without the use of muscle relaxants, were compared in a prospective, controlled, double-blind study. Forty five healthy patients undergoing elective surgery were randomly allocated to receive either 0.9% saline (control), alfentanil 20 micrograms/kg-1, or lignocaine 1.5 mg kg-1 prior to induction with propofol 2.5 mg kg-1. Ease of intubation was scored on a four point scale from 'excellent' = 1 to 'not possible' = 4. Alfentanil pre-treatment allowed intubation in 93% of patients compared to 60% in each of the groups pre-treated with lignocaine or saline. Intubation scores of 1 or 2 were obtained in 14 out of 15 patients (93%) in the alfentanil group and this was significantly better than the lignocaine group (33%) or control group (20%). No difference was detected between the scores of the latter two groups. PMID- 8432276 TI - Myocardial hypertrophy and hyperplasia. A narrative of past, present and future. PMID- 8432277 TI - Deleterious effect of exogenous angiotensin-I on the extent of regional ischaemia and its inhibition by captopril. AB - The endogenous activity of the local renin-angiotensin system (RAS) and the anti ischaemic properties of captopril were investigated in electrically driven rabbit Langendorff hearts (constant pressure: 70 cmH2O, Tyrode solution, Ca2+ 1.8 mmol.l 1). Cumulative concentration-response curves showed no significant difference (P > 0.05) between the reduction of the global coronary flow (CF) by exogenous angiotensin-I or angiotensin-II (EC50 = 10(-10) mol.l-1). It is concluded that the local RAS in isolated rabbit hearts is highly sensitive, whereas its endogenous activity is very low due to very low endogenous angiotensin-I content. Myocardial ischaemia (MI) was induced by the occlusion of a left coronary artery branch and MI was quantified from NADH surface fluorescence photography. MI was significantly enlarged (+35%) (P < 0.05) by exogenous angiotensin-I (6 x 10(-9) mol.l-1). The reduction in CF and the increment in MI by angiotensin-I could be completely prevented by adding captopril at a low concentration (10(-6) mol.l-1) to the perfusion buffer. In the absence of exogenous angiotensin-I, captopril alone (10(-6) mol.l-1) neither significantly enhanced CF (P > 0.05), nor diminished MI (P > 0.05), supporting the finding of very low endogenous activity of the local RAS in this model. We, moreover, conclude that at a low concentration (10(-6) mol.l-1) captopril does not possess direct cardioprotective properties independent of its ACE inhibiting action. PMID- 8432278 TI - Elderly hypertensives and quality of life: some methodological considerations. AB - Management of mild hypertension in the elderly aims at symptom relief and a change in the natural history of hypertension. This is often difficult, since mild hypertension is generally symptomless but drug therapy may have serious quality of life sequelae. Therefore, aspects of patient well-being, including physical, emotional, and social status, should become important treatment considerations, which can be achieved by a patient-specific approach. Quality of life claims for specific drugs appeal to the desire of the prescriber to use the best drug in real-life situations. Physicians generally are guided in their selection of a particular drug for a particular patient by results of clinical trials. This is still difficult to achieve with quality of life studies pertaining to drug management of mild hypertension in the elderly. Few studies have been done, and some do not yield clear results. One needs to study carefully the duration of the trial, the validation of the instruments used, the approach to confounding factors such as inclusion and stratification of elderly by decade of life, inclusion of females in requisite numbers and prior symptoms of patients who, more likely than not, suffer from a host of intercurrent diseases and have been placed on multiple drugs. PMID- 8432279 TI - Rheumatic heart disease in the developing world: prevalence, prevention, and control. AB - Rheumatic heart disease (RHD) continues to be a common health problem in the developing world, causing morbidity and mortality among both children and adults. Although little longitudinal data are available, evidence suggests that there has been little if any decline in the occurrence of RHD over the past few decades. Recent reports from the developing world have documented rheumatic fever (RF) incidence rates as high as 206/100,000 and RHD prevalence rates as high as 18.6/1000. The high frequency of RHD in the developing world necessitates aggressive prevention and control measures. The major interventions for prevention and control include: (1) reduction of exposure to group A streptococci, (2) primary prophylaxis to prevent initial episodes of RF, and (3) secondary prophylaxis to prevent recurrent episodes of RF. Because recurrent episodes of RF cause increasingly severe cardiac complications, secondary prophylaxis is the most crucial feature of an effective RHD programme. For some impoverished countries, secondary prophylaxis may be the only intervention that can realistically be implemented. In addition to this intervention, however, financial and human resources must be committed, and all of these elements must be integrated into existing primary health care systems. Because RHD continues to be a common health problem in the developing world, greater emphasis needs to be placed on the simple and cost-effective prevention and control measures that are currently available to combat this disabling disease. PMID- 8432280 TI - Anomalous origin of the left anterior descending coronary artery from the right sinus of Valsalva associated with effort angina pectoris. AB - A 54-year-old man suffering from effort angina pectoris had an anomalous origin of the left anterior descending coronary artery (LAD) from the right sinus of Valsalva (RSV). The anomalous LAD with a small ostium and without other significant narrowing initially ran into the interventricular septum and subsequently the anterior interventricular groove. Coronary angiography during the anginal attack induced by ergometer exercise testing revealed neither an enhanced narrowing of the LAD ostium, nor myocardial squeezing of the LAD at the interventricular septum level, nor coronary vasospasm. Myocardial ischaemia associated with an anomalous aortic origin of the LAD from the RSV is extremely rare, especially when the vessel runs a septal course. In the present case, the ostial stenosis of the anomalous LAD, probably due to developed atherosclerosis, seemed to be the most likely cause of the exertional angina. PMID- 8432281 TI - Demonstration of the inner structure of a right atrial myxoma by transoesophageal echocardiography. AB - We report a case of a large right atrial myxoma. With the use of transoesophageal echocardiography, several cysts were identified within the tumour and necrotic tissue was differentiated from myxomatous tissue according to its echo-level. Transoesophageal echocardiography was very useful for the precise diagnosis of cardiac tumour and demonstration of the inner structure. PMID- 8432282 TI - Infected right atrial thrombus--an important but rare complication of central venous lines. AB - A case of infected right atrial thrombus is described. Right atrial thrombus is difficult to diagnose and is associated with a high mortality. When it is additionally infected, antibiotics alone are not sufficient treatment and the thrombus should be surgically removed. PMID- 8432283 TI - Polycystic disease of the kidneys complicating the diagnosis of myocardial echinococcosis. AB - The case of a 30-year-old woman with polycystic disease of the kidneys and a large cyst in the interventricular septum is presented. The hypothesis of an echinococcal disease or of a cardiac manifestation of a polycystic disease was raised. The patient's history, serologic data, and the morphological aspect of the cyst did not give evidence for echinococcal disease before surgery. However, the postoperative pathological evaluation confirmed the diagnosis of a single echinococcal cyst. The presented case shows that even in cases without proven diagnosis of echinococcal disease and preexisting hereditary cysts in other organ systems, care should be taken during surgery to avoid anaphylaxis and preoperative spread of the parasite throughout the body. PMID- 8432284 TI - Characteristics of the "Metabolic Syndrome X" in a cardiovascular low risk population in Crete. PMID- 8432285 TI - Systemic embolism. PMID- 8432286 TI - Residual myocardial ischaemia in first non-Q versus Q wave infarction: maximal exercise testing and ambulatory ST-segment monitoring. AB - In a prospective study of 123 consecutive survivors of a first myocardial infarction (43 non-Q wave, 80 Q wave), we determined the total residual ischaemic burden by use of pre-discharge maximal exercise testing and post-discharge 36 h ambulatory ST-segment monitoring initiated 11 +/- 5 days after the infarction. The prevalence of exercise-induced ischaemic manifestations in the infarct types was similar: chest pain 14% vs 16% and ST-segment depression 54% vs 54%. The ischaemic threshold did not differ either (heart rate at 1 mm of ST-segment depression 120 +/- 27 vs 119 +/- 25 beats.min-1). During early post-discharge daily activities, more patients with non-Q wave infarction demonstrated transient episodes of ST-segment depression: 28% vs 14% (ns). Furthermore, ischaemic episodes were significantly longer (42.5 +/- 50.1 vs 22.0 +/- 20.6 min; P < 0.001), and the ischaemic threshold was significantly lower in non-Q wave infarction (heart rate at onset of ST-segment depression 84 +/- 11 vs 88 +/- 9 beats.min-1; P < 0.05). During 3.5 +/- 0.9 years of follow-up the proportion of patients with > or = 1 ischaemic event (non-fatal reinfarction, angina pectoris, revascularization) was significantly higher in non-Q wave infarction (51%) as compared to Q wave infarction (31%) (P < 0.05). In both infarct types the presence of ST-segment depression on ambulatory recording and exercise testing significantly predicted the development of future angina pectoris, whereas patients at increased risk for subsequent non-fatal reinfarction or cardiac death were not identified. PMID- 8432287 TI - Evidence for biventricular involvement in acromegaly: a Doppler echocardiographic study. AB - To investigate left and right ventricular involvement in acromegaly, 20 patients were studied by Doppler echocardiography. Nine of them had systemic hypertension. Right ventricular free wall thickness was significantly increased in acromegalic patients (8 +/- 2 vs 4 +/- 1 mm; P < 0.001). Left ventricular mass index was augmented both in the whole group and in the subgroup of normotensive acromegalics, as compared with normals (134 +/- 33 and 115 +/- 20 vs 80 +/- 18 g.m-2; P < 0.01). Ejection phase indices were normal in the patient group, while impaired left and right ventricular diastolic filling was found. In fact isovolumic relaxation time was prolonged (118 +/- 21 vs 78 +/- 12 ms; P < 0.001), ratio of early to late mitral (0.9 +/- 0.3 vs 1.8 +/- 0.5; P < 0.001) and tricuspid (1.0 +/- 0.2 vs 1.4 +/- 0.3; P < 0.001) flow velocities were significantly decreased as compared with controls. Superior vena cava flowmetry was also abnormal showing a marked decrease of diastolic filling wave and, consequently, of the ratio between peak diastolic and peak systolic flow velocity. No significant differences were observed between normotensive and hypertensive acromegalics, except for left ventricular mass index (115 +/- 20 vs 156 +/- 31 g.m-2; P < 0.01). These findings indicate that abnormal diastolic filling patterns of transmitral, transtricuspid, and superior vena cava flowmetry suggesting 'impaired relaxation' associated with increased left and right ventricular mass, frequently occur in acromegaly. PMID- 8432288 TI - Paradoxical decrease in circulating neuropeptide Y-like immunoreactivity during mild orthostatic stress in subjects with and without congestive heart failure. AB - Neuropeptide Y (NPY) is thought to be co-released with catecholamines in response to major cardiovascular stresses, but its relation to the release of catecholamines in response to minor stresses has been less well described. We therefore studied the response of plasma NPY-like immunoreactivity (NPY-Li) levels to standing (10 min) in eight normal subjects and 11 patients with congestive heart failure, and to short-term (6h) vasodilator therapy in 13 patients with congestive heart failure. In both normal and heart failure patients, NPY-Li-decreased (296 +/- 73 to 233 +/- 63 pg.ml-1 and 652 +/- 36 to 516 +/- 25 pg.ml-1 (P < 0.01) respectively) in response to standing, whereas catecholamines increased in both groups (norepinephrine 203 +/- 73 to 507 +/- 165 pg.ml-1 and 493 +/- 197 to 813 +/- 336 pg.ml-1 (P < 0.001) respectively and epinephrine 23 +/- 12 to 38 +/- 12 pg.ml-1 and 46 +/- 19 to 62 +/- 28 pg.ml-1 (P < 0.001) respectively). Both basal circulating NPY-Li and catecholamine levels were markedly increased in congestive heart failure patients, but catecholamines and NPY-Li did not correlate with each other. After 6 h of nitroglycerin infusion, mean arterial pressure was decreased, but circulating neurohumoral levels remained unchanged and NPY-Li levels decreased (653 +/- 37 to 517 +/- 26 pg.ml-1, P < 0.01). It is concluded that basal circulating NPY-Li and catecholamine levels are increased in congestive heart failure and that this neurohormone could play a concomitant role in the increase in peripheral resistance in these patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8432289 TI - ST segment depression in a VL: a sensitive marker for acute inferior myocardial infarction. AB - In a substantial percentage of patients with acute myocardial infarction, especially in those with inferior wall involvement, no ST elevation is detected on the electrocardiogram. In many of them, ST depression is found in leads oriented to remote segments of the heart. The importance of those reciprocal changes for early diagnosis of acute inferior myocardial infarction in patients without ST elevation has not been stressed. In order to find the prevalence of reciprocal ST depression, we evaluated the admission electrocardiograms of 107 consecutive patients with evolving first acute inferior myocardial infarction. Ninety-three patients had ST elevation of at least 0.1 mV in at least one of the inferior leads: II, III or aVF (group A) and in 14 patients ST displacement did not reach 0.1 mV in any of these leads (group B). In both groups, reciprocal ST depression occurred more frequently in aVL than in any other lead. Only three patients had no ST depression in aVL. In eight patients (7.5%) ST depression in aVL was the sole early electrocardiographic sign of the inferior infarction. aVL is the only lead that is facing the superior part of the left ventricle and thus is the only lead that is truly opponent to the inferior wall. It seems that ST depression in aVL, by contrast to that in the precordial leads, is found in the majority of patients with evolving inferior wall myocardial infarction and is not influenced by extension of the infarction to the right ventricle or to the posterior wall.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8432290 TI - Hypertrophy or hyperplasia in cardiac muscle. Post-mortem human morphometric study. AB - In 103 hearts with various forms of cardiac muscle hypertrophy the following parameters were estimated: diameter, length, volume, density and number of myocytes, and density of myocyte nuclei. The values of all histometric parameters correlated well with left ventricular (LV) weight up to 350 g. In heavier hearts these parameters remained approximately of the same magnitude. The number of myocytes was significantly higher in hearts with LV weight above 250 g. The influence on LV weight of age, coronary artery diameters, degree of atherosclerosis, weight and percent of fibrous tissue was also evaluated. On the basis of a linear discriminant function, hearts were divided into three classes: (1) LV weight < or = 250 g (absence of hyperplasia, hypertrophy only); (2) LV weight 251-350 g (hypertrophy+signs of hyperplasia); (3) LV weight > 350 g (marked signs of hyperplasia). The percent of fibrosis increased proportionally to LV weight. Where LV weight was above 250 g there was a subsequent increase in the mean percent of fibrosis (approx. 26%). This phenomenon (plateau of percent fibrosis) is the result of an increased number of myocytes (myocyte hyperplasia). We suggest that, independent of aetiology, in all hearts above 350 g (patients with congestive heart failure) hyperplasia phenomenon exists. PMID- 8432291 TI - High-dose dipyridamole echocardiography test in coronary artery disease after heart transplantation. AB - In order to evaluate the usefulness of the high-dose dipyridamole echocardiography test (DET) for the detection of coronary artery disease (CAD) after heart transplant and for the assessment of prognosis, 80 heart transplant patients underwent this test within 48 h of the scheduled yearly coronary angiography. Coronary angiography showed normal coronary arteries in 55 patients and CAD in 25, eight of whom had > 50% luminal narrowing. Segmental hypokinesis on baseline echocardiography was present in 27 patients, 19 of whom had CAD (sensitivity = 76%; specificity = 85%). DET was negative in all the patients with normal coronary arteries (specificity = 100%). Out of 25 patients with CAD, eight had a positive DET and 17 a negative DET (sensitivity 32%), but DET was positive in seven of the eight patients with coronary artery stenosis > 50% (sensitivity 87%). During follow-up (9.8 +/- 4.5 months) seven cardiac events occurred in seven patients, all with CAD and wall motion hypokinesis (six on baseline echocardiogram and four after dipyridamole infusion). In our experience, DET does not seem adequate for the screening of post-transplant CAD, but useful in identifying patients with severe lesions (> 50%). Wall motion abnormalities on baseline echocardiogram or after dipyridamole infusion might identify patients who require closer surveillance. A longer experience is needed to confirm these results. PMID- 8432292 TI - Dipyridamole thallium-201 scintigraphy for improved detection of left anterior descending coronary artery stenosis in patients with left bundle branch block. AB - In patients with left bundle branch block (LBBB) undergoing thallium-201 exercise scintigraphy septal perfusion defects are frequently observed irrespective of the presence or absence of coronary artery disease. Consequently, in these patients the specificity for detecting stenoses in the left anterior descending coronary artery (LAD) by thallium-201 scintigraphy is relatively low. It has been hypothesized that pharmacological vasodilation would result in higher specificity than conventional exercise thallium-201 scintigraphy because of a more uniform exploitation of coronary flow reserve. Twenty-five consecutive patients with LBBB underwent dipyridamole thallium-201 imaging and coronary arteriography within 3 months. The prevalence of coronary artery disease was estimated at 48 +/- 19%. Sensitivity for detection of LAD lesions was 100% and specificity was 88%. The positive predictive accuracy and the negative predictive accuracy were 80% and 100% respectively. The 'false positive' septal defects were of the non-reversible type. The appearance of septal perfusion defects was not dependent on changes in heart rate during dipyridamole infusion. This study indicates the value of dipyridamole thallium-201 imaging for non-invasive detection of LAD stenosis in patients with LBBB. PMID- 8432293 TI - Temperature-controlled radiofrequency catheter ablation of AV conduction: first clinical experience. AB - A new technique for catheter ablation of atrioventricular (AV) conduction, using temperature-controlled radiofrequency energy and a bipolar asymmetrical electrode configuration, was applied to 12 patients (mean age, 48 +/- 15 years; range, 18 69 years) with medically refractory atrioventricular nodal reentrant tachycardia (AVNRT) or rapid atrial rhythms. The energy source was a 500 kHz generator with automatic power regulation to a preselected temperature of 80 degrees C. A specially designed 7 F bipolar asymmetric thermo-catheter was used for ablation in all cases. The endpoints of the procedure were: first-degree AV block in patients with AVNRT and third-degree block in patients with atrial fibrillation or flutter. Energy was applied over a range of 1-14 times per patient. After a mean follow-up of 8 +/- 4 months, third- or first-degree AV block persisted in eight patients. In comparison to constant-power radiofrequency ablation, where impedance rises are commonly observed, no impedance rise or coating of the electrode occurred during any of the 97 energy applications in this study. Variable wall contact of the electrode was identified in 20 of 97 applications by a slow temperature rise or a drop in temperature and frequent power adjustments. Thus, monitoring temperature and automatic power regulation may help to reduce the total delivered energy. Temperature control during radiofrequency energy avoids coagulum formation and consequently the associated potential hazards of constant-power application. PMID- 8432294 TI - Coronary angioplasty in cardiac transplant recipients. AB - Accelerated coronary artery disease following cardiac transplantation remains an important obstacle to long-term survival and the correct management strategy remains unclear. This observational, prospective study was designed to examine the feasibility of using percutaneous transluminal coronary angioplasty (PTCA) in the treatment of post-transplant coronary disease. Thirteen consecutive patients were selected from the total population of 276 transplant recipients who underwent routine coronary angiography between 1987 and 1990. Selection of patients was on angiographic criteria alone and PTCA was performed to all accessible stenoses with more than 80% luminal narrowing. PTCA was performed using standard angioplasty equipment and procedure as considered appropriate for the individual lesion. A successful PTCA was defined as more than 30% reduction in luminal narrowing and a residual narrowing of less than 50%. Restenosis was defined as a loss of 50% or more of the gain achieved at the time of successful PTCA or more than a 30% increase in narrowing at the site of stenosis. A total of 31 lesions were dilated in this group and a successful result was achieved in 29 of these (93%) and in 12 of the 13 patients. The one patient with failed PTCA underwent later successful coronary artery bypass grafting to complete revascularization. Four of the 13 patients have had two angioplasty procedures, two for restenosis and two for disease progression in other sites. One patient died 15 months after the initial PTCA and the remaining 12 were asymptomatic with good exercise tolerance and ventricular function at a mean of 19 months (range 1 39 months) following first PTCA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8432295 TI - Intra-aortic balloon counterpulsation improves survival in cardiogenic shock complicating acute myocardial infarction. AB - The impact of intra-aortic balloon counterpulsation (IABC) on survival of patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) has been evaluated in this study of 85 patients. IABC was available for the 24 group A patients (and used in 20 patients). IABC was not available for the 21 group B patients who presented simultaneously with similar clinical characteristics and received identical pharmacological treatment. In-hospital and one year survival was significantly higher in group A (46% and 38% vs 19% and 10%, P < 0.001). Sixteen out of the 20 (group A1) IABC patients received early coronary revascularization. During 1980-1984, 35 patients with AMI and CS received IABC (group C) but none underwent early revascularization. There was no difference in in-hospital or one-year survival between group A1 (50% and 40%) and group C (45% and 40%). We conclude that early IABC improves survival of patients with AMI complicated by CS. PMID- 8432296 TI - Cost effectiveness of thrombolytic treatment for myocardial infarction: comparison of anistreplase, alteplase and streptokinase in 270 patients treated within 4 hours. AB - Two hundred and seventy patients, under 71 years of age and suffering from a less than 4 h infarction diagnosed according to clinical and electrocardiographic criteria, were included: two 90-patient groups were randomized and then treated with either anistreplase (30 mg iv over 5 min) or alteplase (10 mg bolus injection + 5000 IU heparin bolus injection, followed by 90 mg alteplase over 3 h), and compared with a consecutive control series of 90 patients treated with streptokinase (1.5 million U over 1 h). Intravenous heparin and aspirin (250 mg day-1) were then prescribed routinely. The three groups were comparable as regards age (55.2 +/- 10 years), male/female ratio (10.4), the site of the infarction (42% anterior, 55% inferior) and initial clinical seriousness (Killip I = 90%, II = 8%, III = 2%). The patients were thrombolysed in 17 community hospitals, and then referred to a university hospital with catheterization facilities. An efficacy score was determined, based on four parameters: two obtained from coronary angiography and left ventriculography performed on day 6 +/- 2 (N = 252) (asynergic score and patency of the infarct-related artery), one from Tl-tomography performed at rest (infarct size) and one from radionuclide angiography (global left ventricular ejection fraction) performed between day 15 and day 21 (N = 242). The score (range: 0-24 per patient) was 17.8 +/- 6.4 for alteplase, 17.7 +/- 6.0 for anistreplase and 18.1 +/- 6.0 for streptokinase respectively (NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8432297 TI - ECAT angina pectoris study: baseline associations of haemostatic factors with extent of coronary arteriosclerosis and other coronary risk factors in 3000 patients with angina pectoris undergoing coronary angiography. AB - The ECAT Angina Pectoris Study is a European multicentre study investigating the pathogenetic and possibly predictive role of the haemostatic system in the progress of coronary heart disease. In this paper we report the cross-sectional analysis of haemostatic factors in 3043 patients, who underwent coronary angiography due to angina pectoris. Fibrinogen levels were higher in patients with one or more coronary stenoses of at least 50% than in patients without, by an average of 0.16 g.l-1 (P < 0.0001). Depressed fibrinolytic activity due to higher levels of PAI was also associated with the presence of coronary stenoses. There was no association with the extent of coronary arteriosclerosis, as assessed by the number of involved arteries, except that patients who had more vessels with total occlusions had higher fibrinogen levels. Depressed fibrinolytic activity was also clearly associated with diabetes, obesity, higher triglyceride levels, smoking and impaired cardiac pump function as assessed by ejection fraction. Cholesterol levels were particularly correlated with protein C and plasminogen. PMID- 8432298 TI - Raised levels of antistreptokinase antibody and neutralization titres from 4 days to 54 months after administration of streptokinase or anistreplase. AB - Streptokinase and anistreplase are antigenic and their administration often leads to antibody formation. These can cause allergic reactions and/or neutralization of streptokinase with resulting suboptimal treatment. Currently, streptokinase re administration is considered appropriate for up to 5 days and from 1 year after a previous dose. Antistreptokinase antibody and neutralization titres (NT) were measured in three groups of patients to determine if this practice is appropriate: 1. (early)--36 patients whose titres were measured for at least 5 days after thrombolysis; 2. (late)--57 patients who received thrombolysis 12-54 months previously; 3. (controls)--182 consecutive suspected myocardial infarction patients (without previous exposure to thrombolysis). Results were as follows (mean +/- SEM): 1. (early)--the antibody and/or NT were raised by day 4 in 19.4% of the patients. One patient could have neutralized 1.97 million units (MU) of streptokinase by day 4. (Day 4--antibody 1:39 +/- 11, NT 0.19 +/- 0.05 MU; day 5- 1:136 +/- 41 and NT 0.7 +/- 0.43 MU respectively.) 2. (late)--23 patients (40%) had either antibody titres > or = 1:160 and/or NT > 1.5 MU. (12-23 months- antibody 1:243 +/- 43, NT 0.63 +/- 0.15 MU; 24-35 months--1:98 +/- 31 and 0.69 +/ 0.22 MU; 36-54 months--1:87 +/- 14 and 0.54 +/- 0.12 MU.) All titres were significantly higher than the controls (antibody 1:25 +/- 3, NT 0.14 +/- 0.01 MU, P < 0.01). After streptokinase or antistreplase, antibodies are raised from 4 days to at least 54 months. It would seem prudent to avoid their re administration during this time interval. PMID- 8432299 TI - Early administration of captopril and nitroglycerin in combination after acute myocardial infarction: an invasive haemodynamic study. AB - The combination of captopril and nitroglycerin early after acute myocardial infarction (AMI) could lead to a dangerous decrease in blood pressure coronary perfusion. To evaluate the safety aspects and haemodynamic effects of this combination, we studied 36 first 'Q wave' thrombolysed anterior wall AMI patients during the 24 h following the onset of symptoms. Afterwards, thrombolysis patients received a continuous infusion of nitroglycerin and were submitted to pulmonary artery catheterization. Those patients with mean arterial pressure (MAP) > or = 70 mmHg, cardiac index > or = 2.2 l.min-1.m-2, and wedge pressure > or = 10 mmHg were included and randomized to receive 6.25 mg of captopril every 6 h on the first day and 12.5 mg qid on the second if MAP > or = 70 mmHg (group 1). A second group (group 2) received a placebo. Haemodynamic parameters were determined after 1, 6 and then every 6 h up to 48 h after basal measurements. Significant differences were observed only for the MAP and the rate-pressure product (reduction in group 1 values, P < 0.05). However, MAP was maintained within acceptable limits. Our data support the fact that the combination of captopril and nitroglycerin in the early hours of a non-complicated anterior wall AMI is safe, and could guarantee its use in large clinical trials to determine the effects on left ventricle remodelling and survival after AMI. PMID- 8432300 TI - A mechanism of cardiac pain suppression by spinal cord stimulation: implications for patients with angina pectoris. AB - Clinical reports show that electrical stimulation of the spinal cord reduces symptoms of angina pectoris, but so far have not provided evidence on the mechanisms involved. The hypothesis for this study was that inhibition of spinothalamic tract transmission may account for this result. Extracellular potentials of 28 spinothalamic tract neurons were recorded in anaesthetized monkeys, and the effects of dorsal column stimulation were determined on activity evoked by cardiac and somatic stimuli. Dorsal column stimulation reduced the number of cell potentials evoked by electrical stimulation of cardiopulmonary sympathetic afferent fibres in 11 spinothalamic tract cells tested. Activity evoked by intracardiac injection of bradykinin was decreased by dorsal column stimulation in six of seven neurons that responded to chemical stimulation of afferents. Differential effects of dorsal column stimulation were correlated to the cell responses to somatic field stimulation. Dorsal column stimulation inhibited activity in 12 of 12 neurons which were excited only by noxious pinch of somatic fields, whereas eight of 16 neurons which were excited by innocuous brushing of somatic fields were unaffected or excited. Transection of the dorsal column showed that the pathway transmitting inhibitory impulses descended from the stimulation site to the spinothalamic tract neurons examined. Results of this study are consistent with the concept that spinal cord stimulation reduces pain by decreasing the firing of spinothalamic tract cells which are activated by small fibre afferents. The paresthesias associated with nerve stimulation techniques may result from activation of spinothalamic tract cells which are excited by large fibre afferents. The clinical decision to employ spinal cord stimulation in patients with angina should balance the obvious benefit of pain relief against the risk of depriving the patient of an important warning signal while active myocardial ischaemia is in progress. PMID- 8432301 TI - Examining the instructional contexts of students with learning disabilities. AB - This review of the literature examines how instructional contexts for elementary and secondary level students with learning disabilities have been studied in the past 10 years through a variety of methodological approaches and observation instruments. These studies employed some direct measure of classroom ecology, as well as some measure of the teacher or students' classroom behavior. Information included the time that students were engaged in different activities in different settings, interactions between teachers and students, and students' classroom behavior. PMID- 8432302 TI - Factors influencing the social status of children with mild academic disabilities in regular classrooms. AB - This article discusses the development and evaluation of a model of social status which has implications for students both with and without mild academic disabilities in integrated classrooms. Behavioral data relating to peer social status were collected from peers, teachers, and independent observers for 97 students with disabilities and 97 without disabilities from the same regular elementary school classes. Path analysis indicated that teachers' attitudes toward integration were not related to the social status of the students with disabilities. However, teacher perceptions of academic behavior, peer perceptions of academic behavior, and peer perceptions of disruptive behavior were found to be related to social status for both groups of students. PMID- 8432303 TI - Group evaluation: a collaborative, peer-mediated behavior management system. AB - The efficacy of a consensus based group-evaluation system was examined using a reversal design. Two groups of students with disabilities served as subjects. The group-evaluation system involved: (a) dividing the groups into teams; (b) having each team agree on a common rating for the group's behavior during a specified time period; (c) comparing each team's rating to the teacher's rating; and (d) delivering reinforcement to each team based on the group's behavior and the team's accuracy in rating the group's behavior. Results indicated that the group evaluation system was an effective strategy for modifying classroom behavior. PMID- 8432304 TI - Educational services for children with chronic illnesses: perspectives of educators and families. AB - Two parallel studies examined schools' and families' perceptions of the needs of children with chronic illnesses. Samples of 80 California school districts and 72 families were interviewed regarding types of chronic illnesses and school services, perceptions of and barriers to services, strategies for overcoming barriers, and fears and concerns of children with chronic illnesses. Most students were served in regular classes or at home. The most common barriers named by districts were funding and lack of public and staff awareness. Barriers named by families included teachers' misunderstanding of the child's needs and misinformation about the illness. Families focused on social-emotional issues and the impact of illness on their child's life; districts emphasized school absences and falling behind in schoolwork. PMID- 8432305 TI - Adult adjustment among high school graduates with mild disabilities. AB - This study investigated the adult adjustment of a statewide random sample of 737 young adults with learning disabilities, 59 labeled behaviorally disordered, and 142 labeled mentally disabled, all graduates of special education resource teacher programs. Results are reported in terms of (a) general status information, such as marital status and living arrangements; (b) information about those competitively employed, such as wages, hours worked per week, and percentage of living expenses paid; and (c) comparison of competitively employed versus unemployed individuals, in terms of high school vocational training and work experiences. Information is also provided on postsecondary education and overall "successful" adult adjustment. Data are compared across disability groups and across gender, where relevant. PMID- 8432306 TI - Learning disabilities and social competence: a social ecological perspective. AB - To explore the relationship between learning disabilities (LD) and social competence, various indexes of social and academic competence were collected from a sample of students with LD, as well as a matched sample of children without disabilities, in Grades 3-6. Measures included academic grades, teacher perceptions, peer perceptions, self-perceptions, social network outside of school, and direct observation of social interactions. Results suggest that children with LD differ from children without disabilities on virtually all indexes of academic competence, regardless of social status. In the social domain, children with LD had higher self-concept scores than did children without disabilities. Most social differences were linked to the child's peer status, independent of disability. PMID- 8432307 TI - Relationships among states' fiscal and demographic data and the implementation of P.L. 94-142. AB - This study examined the relationships between state-level fiscal and demographic variables and identification rates and cumulative placement rates for certain categories of special education students in 1976, 1980, and 1983. The study explored the feasibility of using extant national data to study implementation of special education programs. Identification rates for students with learning disabilities and emotional disturbance were associated with level of state per capita income and proportion of rural school-age population. States with higher per-capita income tended to have higher cumulative placement rates in special classes and all more restrictive settings. PMID- 8432308 TI - Role of protein kinase C in bradykinin-induced prostaglandin formation in osteoblasts. AB - Bradykinin (1 microM, 5 min) induced translocation of protein kinase C (PKC) to the plasma membrane fraction in osteoblastic MC3T3-E1 cells. Bradykinin also enhanced the binding of phorbol 12,13-dibutyrate (PDBu) to intact cells, a measure of PKC activation. Addition of bradykinin (1 microM) to cells preincubated with [3H]PDBu (10 nM, 20 min) caused an increase in specific PDBu binding that was maximal after 5-10 min. The bradykinin-induced enhancement of PDBu binding was seen at 1 nM and was maximal at 10 nM. The bradykinin B1 receptor agonist des-Arg9-bradykinin (1 microM) did not enhance specific PDBu binding to intact MC3T3-E1 cells. PDBu at and above 3 nM stimulated the formation of prostaglandin E2 (PGE2) in MC3T3-EI cells. This stimulatory effect was seen after 15-20 min incubation. The Ca2+ ionophore A23187 at and above 1 microM induced a rapid (within seconds) burst of PGE2 formation in MC3T3-E1 cells. The effect of PDBu and A23187 on PGE2 formation was synergistic. The PKC inhibitor staurosporine (200 nM) inhibited basal as well as bradykinin-induced prostaglandin-formation in MC3T3-E1 cells. IN CONCLUSION: bradykinin enhances PKC activation in osteoblastic MC3T3-E1 cells. This kinase activation may be involved in bradykinin-induced prostaglandin formation. PMID- 8432310 TI - Enhancement by captopril of bradykinin-induced calcium transients in cultured endothelial cells of the bovine aorta. AB - Using microscopic fluorometry and fura-2-loaded cultured bovine aortic endothelial cells, we determined the effects of captopril, an angiotensin converting enzyme (ACE) inhibitor, on bradykinin-induced Ca2+ transients in endothelial cells. In the presence of extracellular Ca2+, 10(-9) M bradykinin induced an early rise in the transients followed by sustained elevations of cytosolic calcium concentration ([Ca2+]i). Bradykinin concentration-dependently increased [Ca2+]i (EC50 6.7 x 10(-9) M). Captopril, 10(-5) M, enhanced and prolonged the bradykinin-induced Ca2+ transients and shifted the concentration response curve to the left (EC50 8.5 x 10(-10) M). In porcine coronary aterial strips with intact endothelium, cumulative applications of bradykinin induced an endothelium-dependent relaxation during prostaglandin F2 alpha-induced contraction (EC50 = 2.0 x 10(-9) M). Treatment with 10(-5) M captopril enhanced the bradykinin-induced relaxation and shifted the concentration-response curve to the left (EC50 = 7.6 x 10(-10) M). Thus, captopril enhances the bradykinin induced relaxation by mechanisms mainly dependent on the endothelium, namely the inhibition of ACE. PMID- 8432309 TI - Differences between rat dorsal and ventral hippocampus in muscarinic receptor agonist binding and interaction with phospholipase C. AB - Carbachol, a full muscarinic receptor agonist, stimulated [3H]inositol phosphate accumulation in both the ventral and dorsal hippocampus, but its efficacy and affinity were higher in the former area. The partial agonist oxotremorine had a weak stimulatory effect in both regions. The affinity profiles of pirenzepine and AF-DX 116 in antagonizing carbachol-stimulated [3H]inositol phosphate accumulation indicated that M1 and M3 receptors contributed equally to the response in either region. On the other hand, there were no differences in the receptor density, or in the distribution of muscarinic receptor subtypes between the two regions of the hippocampus which could account for the effect as determined in binding experiments with selective antagonists. Analysis of carbachol binding curves did, instead, indicate a difference in the way the agonist interacted with the receptors within the hippocampus, i.e., carbachol recognized three agonist affinity states (superhigh, high and low) in the ventral hippocampus, and only two (high and low) in the dorsal part. The findings thus suggested that the regional diversity in the efficacy of carbachol in stimulating phosphoinositide turnover was related to the complexity with which it bound to muscarinic receptors. Transduction processes that intervene between changes in the muscarinic receptors' conformation and activation of phospholipase C might be relevant to these differences. PMID- 8432311 TI - Ca2+ channel blocking activity of lacidipine and amlodipine in A7r5 vascular smooth muscle cells. AB - Inhibition of the K(+)-stimulated increase in cytosolic free Ca2+ by a series of 1,4-dihydropyridines was evaluated in A7r5 vascular smooth muscle cells loaded with the fluorescent Ca2+ indicator fura-2 acetoxymethyl ester. The IC50 of the drugs, added to suspended cells 3 min before 150 mM KCl, gave the following order of potency: lacidipine (2.76 nM) > nitrendipine (3.81 nM) > amlodipine (4.56 nM) > nifedipine (10.08 nM). A7r5 cells were also exposed to the 1,4 dihydropyridines, at their IC50, for 25 min, and then repeated washout cycles were performed before adding KCl. The Ca2+ channel blocking activity of nifedipine and nitrendipine gradually diminished, disappearing after four washout cycles 25, 55, 115 and 175 min after drug treatment. Amlodipine and lacidipine displayed slow onset and offset of antagonism, their activity becoming stronger with time, in spite of the repeated washes. [3H]Lacidipine was avidly and promptly entrapped in A7r5 cells and was not removed by washout. However, its potency as a Ca2+ channel blocker was not directly related to the amount of drug locked in the cell since it increased with time, indicating that lacidipine binds to the lipid bilayer of the cell membrane and then gradually diffuses towards a specific binding site. This model can, therefore, predict the Ca2+ blocking properties of 1,4-dihydropyridines with slow onset and offset of antagonism and could be employed to evaluate compounds selective for vascular smooth muscle. PMID- 8432312 TI - Studies on the effects of several pentamidine analogues on the NMDA receptor. AB - We have investigated the interactions of six analogues of pentamidine with the N methyl-D-aspartate (NMDA) receptor complex. All six compounds were effective NMDA receptor antagonists based upon their ability to inhibit [3H]dizocilpine binding to rat brain membranes. IC50 values ranged from 2 to 18 microM, and all compounds had Hill coefficients in excess of 1 suggesting a non-competitive interaction with [3H]dizocilpine. All compounds also inhibited NMDA- and glycine-induced intracellular Ca2+ changes measured in cultured rat forebrain neurons using the fluorescent indicator, fura-2. IC50 values in this assay ranged from 0.4 to 4.7 microM. Whereas pentamidine is directly toxic to cultured neurons, this was not a consistent finding with the pentamidine analogues tested, indicating that the toxic effects are not related to NMDA receptor antagonism. Finally, all of the agents tested were also effective in protecting neurons from NMDA-induced neurotoxicity. These data emphasize the possible utility of pentamidine-like drugs as neuroprotective agents and suggest that it is possible to generate compounds with a wider margin of safety than pentamidine itself. PMID- 8432313 TI - A prospective study of exposure to verotoxin-producing Escherichia coli among Canadian children with haemolytic uraemic syndrome. The CPKDRC co-investigators. AB - Haemolytic uraemic syndrome (HUS) is a leading cause of acute renal failure in childhood. Although infection with Escherichia coli O 157. H7 has been associated with HUS in North America and Europe, only a limited number of studies have examined the role of other verotoxin-producing E. coli (VTEC) serotypes in this condition. To address this issue, we conducted a comprehensive, prospective microbiological study of patients treated for HUS at eight Canadian hospitals in the summer of 1990. Of the 34 consecutive patients with HUS enrolled over 4 months, E. coli O 157. H7 was isolated from the stools of 26, and other E. coli serotypes were isolated from four patients. In four subjects no pathogenic E. coli serotypes were identified on stool culture. Using oligonucleotide probes specific for VT-1 and VT-2, verotoxin genes were detected in the stool isolates of all patients with E. coli O 157. H7, and from two with other E. coli serotypes. Two other patients had at least a fourfold rise in anti-verotoxin antibodies. Strong evidence of exposure to a verotoxin was present in 30/34 (88%). Patients with E. coli O 157. H7 infection were more likely to develop an antibody response to VT-2 than to VT-1 (22/22 vs 12/22; P = 0.002). These results further strengthen the association of HUS with verotoxin-producing E. coli in North America, and confirm that E. coli serotypes other than O 157.H7 are isolated in a small proportion of summertime HUS episodes. PMID- 8432314 TI - Outbreak of Legionnaires' disease at University Hospital, Nottingham. Epidemiology, microbiology and control. AB - Twelve patients in a large teaching hospital contracted Legionnaires' disease over a period of 11 months. The source was a domestic hot water system in one of the hospital blocks, which was run at a temperature of 43 degrees C. Five different subtypes of Legionella pneumophila serogroup 1 have been isolated from water in different parts of the hospital, over a period of time. Only one subtype, Benidorm RFLP 14, was implicated in disease. Circumstantial evidence suggested that the outbreak may have been due to recent colonization of the hot water system with a virulent strain of Legionella pneumophila. The outbreak was controlled by raising the hot water temperature to 60 degrees C, but careful surveillance uncovered two further cases in the following 30 months. Persistent low numbers of Legionella pneumophila were isolated from the domestic hot water of wards where Legionnaires' disease had been contracted, until an electrolytic unit was installed releasing silver and copper ions into this supply. PMID- 8432315 TI - Molecular epidemiology of the plasmid-encoded TEM-1 beta-lactamase in Scotland. AB - A survey of the beta-lactamases responsible for ampicillin resistance in urinary Escherichia coli isolated in central Scotland has been performed. The TEM-1 beta lactamase was found to be most prevalent occurring in 88.2% of ampicillin resistant isolates tested. Forty-six percent of the TEM-1 producing strains were able to transfer this resistance to E. coli J62-2 at 37 degrees C. Analysis of the resulting transconjugants revealed that the degree of resistance to amoxycillin and amoxycillin in combination with clavulanic acid was related to the specific activity of the TEM-1 beta-lactamase. The variation in specific activity was shown to be related to plasmid type as determined by restriction analysis. No obvious relationship between beta-lactamase specific activity and resistance to amoxycillin and amoxycillin plus clavulanic acid could be demonstrated in the original plasmid donor strains. PMID- 8432316 TI - Maternal prevalence of Toxoplasma antibody based on anonymous neonatal serosurvey: a geographical analysis. AB - A total of 12,902 neonatal samples collected on absorbent paper for routine metabolic screening were tested anonymously for antibodies to toxoplasma. Seroprevalence varied from 19.5% in inner London, to 11.6% in suburban London, and 7.6% in non-metropolitan districts. Much of this variation appeared to be associated with the proportions of livebirths in each district to women born outside the UK. However, additional geographical variation remained and seroprevalence in UK-born women was estimated to be 12.7% in inner London, 7.5% in suburban London, and 5.5% in non-metropolitan areas. These estimates are considerably lower than any previously reported in antenatal sera in the UK. The wide geographical variation highlights a need for further research to determine the relative importance of different routes of transmission. PMID- 8432317 TI - Occurrence of oocysts of Cryptosporidium sp. in Larus spp. gulls. AB - Between November 1990 and February 1991 101 gull faecal samples, collected in central Scotland, and 50 cloacal lavages, from gulls captured at two refuse tips near Durham, England were examined for the presence of Cryptosporidium sp. oocysts. Five of 101 (c 5%) of faecal samples and 11 of 50 (22%) of cloacal lavages contained oocysts, of which 64% and 83%, respectively were considered viable when examined with propidium iodide and 4'-6-diamidino-2-phenylindole. Since there is insufficient evidence to ascribe these oocysts to a recognized species they are therefore referred to as Cryptosporidium sp. oocysts. There were significant differences in the occurrence of oocysts between gulls captured at the different refuse tips (P < or = 0.01), but no significant difference between the distribution of oocysts in two species of gull, Larus argentatus (Herring Gull) and L. ridibundus (Black-head Gull). The differences may be explained by different food sources and feeding habits. The contribution of gulls to environmental contamination with Cryptosporidium sp. oocysts is probably generally small, but may be more significant when large numbers roost on surface waters. PMID- 8432318 TI - Acute respiratory illness in the community. Frequency of illness and the agents involved. AB - Investigations of respiratory illnesses and infections in Tecumseh, Michigan, USA, were carried out in two phases, together covering 11 years. During the second phase, there were 5363 person-years of observation. Respiratory illness rates in both males and females peaked in the 1-2 year age group and fell thereafter. Adult females had more frequent illnesses than adult males; illnesses were less common in working women than in women not working outside the home. Isolation of viruses fell with increasing age; rhinoviruses were the most common isolate. Influenza infection rates, determined serologically, suggested relative sparing of young children from infection with type A (H1N1) and type B. Infection rates were highest in adult age groups for type A (H3N2). The isolation and serological infection rates were used to estimate the extent to which laboratory procedures underestimated the proportion of respiratory illnesses caused by each infectious agent; data from other studies were also used in this estimation. Severity of respiratory illnesses was assessed by the proportion of such illnesses that resulted in consultation of a physician. Rhinoviruses produced the greatest number of consultations. Overall, physician consultations were associated with 25.4% of respiratory illnesses. PMID- 8432319 TI - A comparison of Salmonella enteritidis phage types from egg-associated outbreaks and implicated laying flocks. AB - Infections due to Salmonella enteritidis are increasing worldwide. In the United States, between 1985 and 1989, 78% of the S. enteritidis outbreaks in which a food vehicle was identified implicated a food containing raw or lightly cooked shell eggs. Under a US Department of Agriculture regulation published in 1990, eggs implicated in human food-borne S. enteritidis outbreaks were traced back to the source flock. The flock environment and the internal organs of a sample of hens were tested for S. enteritidis. We compared the S. enteritidis phage types of isolates from 18 human, egg-associated outbreaks and the 15 flocks implicated through traceback of these outbreaks. The predominant human outbreak phage type was recovered from the environment in 100% of implicated flocks and from the internal organs of hens in 88% of implicated flocks we tested. The results support the use of phage typing as a tool to identify flocks involved in human S. enteritidis outbreaks. PMID- 8432320 TI - Vaccination against hepatitis B: comparison of intradermal and intramuscular administration of plasma derived and recombinant vaccines. AB - A retrospective analysis of levels of antibody to hepatitis B surface antigen in 1419 health care workers was carried out to compare the efficacy of intramuscular and intradermal administration of plasma derived and recombinant hepatitis B vaccines. No significant difference was detected between the response to intradermal and intramuscular plasma derived vaccine. However of those who received intramuscular recombinant vaccine 81.6%, 13.8% and 4.7% were good (> or = 100 miu/ml), low (10-99 miu/ml) and non-responders (< 10 miu/ml) respectively, compared with 51.1%, 29.8% and 19.2% of the intradermal group (P < 0.0001). Low dose intradermal administration of recombinant vaccine did not produce satisfactory levels of antibody to hepatitis B surface antigen. PMID- 8432321 TI - A large salmonellosis outbreak associated with a frequently penalized restaurant. AB - Between January and June 1990, Restaurant A in Greenville, South Carolina repeatedly failed local health department inspection and was repeatedly sanctioned. In September 1990, two persons, hospitalized with salmonellosis after attending a convention catered by Restaurant A, contacted the South Carolina Department of Health and Environmental Control. We inspected Restaurant A, interviewed food handlers, and surveyed by telephone persons from every sixth business attending the convention. Of 398 persons interviewed, 135 (34%) reported gastroenteritis. Nine had culture-confirmed salmonella infection. People who ate turkey were 4.6 times more likely to become ill than those who did not eat turkey (95% confidence interval 2.0, 10.6). We estimate that of 2430 attendees, 824 became ill. Sanitarians judged Restaurant A's kitchen too small to prepare over 500 meals safely. The cooked turkey was unrefrigerated for several hours, incompletely rewarmed, and rinsed with water to reduce its offensive odour prior to serving. Stronger sanctions may be needed against restaurants that repeatedly fail local health department inspection. PMID- 8432322 TI - Iron restriction and the growth of Salmonella enteritidis. AB - Strains of Salmonella enteritidis were examined for their ability to remove ferric-ions from the iron chelating agents ovotransferrin, Desferal and EDDA. Growth of S. enteritidis phage type (PT) 4 (SE4) in trypticase soy broth containing ovotransferrin resulted in the expression of iron regulated outer membrane proteins (OMPs) of 74, 78 and 81 kDa, and unexpectedly the repression of expression of OMP C. The 38 MDa 'mouse virulence' plasmid was not required for the expression of the iron-regulated OMPs (IROMPs). SE4 was able to obtain iron bound to the iron chelator Desferal and EDDA without expressing a high-affinity iron uptake system. Strains of S. enteritidis belonging to PTs 7, 8, 13a, 23, 24 and 30 were also able to remove ferric ions from Desferal and EDDA without expressing a high-affinity iron uptake system. We conclude that strains of SE4 possess a high-affinity iron sequestering mechanism that can readily remove iron from ovotransferrin. It is likely that iron limitation, and not iron restriction, is responsible for the bacteriostatic properties of fresh egg whites. PMID- 8432323 TI - Salmonella enteritidis outbreak in a restaurant chain: the continuing challenges of prevention. AB - In 1990, a Salmonella enteritidis (SE) outbreak occurred in a restaurant chain in Pennsylvania. To determine its cause(s), we conducted a case-control study and a cohort study at one restaurant, and a survey of restaurants. Egg dishes were associated with illness (P = 0.03). Guests from one hotel eating at the restaurant had a diarrhoeal attack rate of 14%, 4.7-fold higher than among those not eating there (P = 0.04). There were no differences in egg handling between affected and unaffected restaurants. Eggs supplied to affected restaurants were medium grade AA eggs from a single farm, and were reportedly refrigerated during distribution. Human and hen SE isolates were phage type 8 and had similar plasmid profiles and antibiograms. We estimate the prevalence of infected eggs during the outbreak to be as high as 1 in 12. Typical restaurant egg-handling practices and refrigeration during distribution appear to be insufficient by themselves to prevent similar outbreaks. PMID- 8432324 TI - Epidemiology of typhoid fever in Singapore. AB - A total of 1452 cases of typhoid fever was notified in Singapore from 1980-9. The morbidity rates of indigenous cases showed a steady decline from 5.9 per 100,000 population in 1980 to 1.2 per 100,000 population in 1989. The mean case fatality was 0.8%. Children, adolescents and young adults were most susceptible to typhoid fever. There was no significant difference in morbidity rates between the major ethnic groups. The vast majority of indigenous cases were sporadic while outbreaks accounted for almost one third of them. Food was the main vehicle of transmission. The commonest indigenous phage types were B1, D1 and A. Antimicrobial resistance was infrequently seen. The proportion of imported cases rose from 32% in 1980 to 72% in 1989. Almost half (48.5%) of all imported cases were local residents who contracted typhoid fever while travelling in endemic countries. As imported cases assume greater importance in the epidemiology of typhoid fever in Singapore, further drop in typhoid fever incidence would require reduction of travel-related cases through greater awareness of food hygiene and effective vaccination. PMID- 8432325 TI - The carriage of Streptococcus suis type 2 by pigs in Papua New Guinea. AB - An indirect fluorescent antibody test was used to detect the presence of Streptococcus suis type 2 in nasal and pharyngeal swabs taken from pigs in Papua New Guinea. The rate of carriage for the two sites in domesticated indigenous village pigs was 0.5 and 2.5% respectively, compared to 39 and 43% for intensively reared pigs. These findings were supported by the results of a serological survey, using an enzyme linked immunosorbent assay, in which 87% of intensively reared pigs but only 8% of village pigs were seropositive to S. suis type 2. It is proposed that in intensive piggeries S. suis type 2 is continually cycled between pigs. In village pigs, the low population density and harsh environmental conditions prevents this cycle of infection. PMID- 8432326 TI - Crystal violet reactions of Staphylococcus aureus strains colonizing infants in the first six weeks. AB - Nasal colonization with Staphylococcus aureus occurred in 18% of babies leaving a maternity unit and had risen to 40% by 6 weeks after birth. S. aureus was first acquired by 34.5% of babies after discharge. Female infants were more likely to be colonized than males. Colonization was not significantly different between babies receiving standard postnatal care and those nursed on the Special Care Baby Unit. Crystal violet (CV) tests showed that purple-reacting isolates accounted for approximately 60% of strains, whether first detected at hospital discharge or subsequently acquired. Purple-reacting strains, once acquired, were significantly better able to persist than non purple-reacting strains and formed a cumulatively higher proportion of the strains isolated at 6 weeks after birth than at hospital discharge. CV purple-reactions were significantly associated with lysis by phages of groups III and I and non-purple-reactions were significantly associated with lysis by phages of group II and/or 94/96. Maternity units remain a significant route whereby strains of S. aureus with some characteristics associated with a hospital origin gain access to the community. PMID- 8432327 TI - Sialic acid content and surface hydrophobicity of group B streptococci. AB - The sialic acid content and the cell-surface hydrophobicity index of 40 group B streptococci (GBS) strains were assessed. GBS isolated from invasive infections (virulent strains) presented an increased level of sialic acid content (1.4%) when compared with GBS isolated from asymptomatic patients (0.53%). Treatment of GBS strain 85634 with neuraminidase resulted in a decrease (about 25%) in the net negative surface charge as assessed by cell electrophoresis. This finding suggests that sialic acid residues are important anionogenic groups exposed on GBS cell surface. N-acetylneuraminic acid was the only sialic acid derivative characterized in the strain 85634 as evaluated by gas-liquid chromatography. GBS from different serotypes presented a hydrophobic index mean value of 0.9. Even though the sialic acid contributed effectively to the negative charge on GBS cell surface, no difference was observed in the hydrophobic index when virulent and avirulent strains were compared. PMID- 8432328 TI - Diarrhoea in close contacts as a risk factor for childhood haemolytic uraemic syndrome. The CPKDRC co-investigators. AB - To determine whether the risk factors for childhood haemolytic uraemic syndrome (HUS) are similar to risk factors previously reported for Escherichia coli O 157. H7 gastroenteritis, we conducted a case-control study at eight paediatric hospitals in the summer of 1990. Thirty-four consecutive children with HUS were prospectively enrolled; all had diarrhoea and 88% had laboratory evidence of exposure to verotoxin-producing E. coli (VTEC). The 102 controls were otherwise healthy children with minor acute injuries. Parents of all subjects responded to a questionnaire about each child's exposure to various foods, methods of food preparation, sources of water, travel, and individuals with diarrhoea. Children with HUS were significantly more likely than controls to have had close contact with an individual with diarrhoea in the 2 weeks before the onset of illness (74 v. 29%, P < 0.00001; odds ratio 7.0, 95% CI 2.7-18.5). The onset of diarrhoea in the contacts occurred a median of 6 days (range, 1- > 14 days) before the onset of diarrhoea in the HUS patients. Exposure to undercooked ground meat was not significantly more common in the patients with HUS (15 v. 8%; P = 0.05). These data provide evidence consistent with person-to-person transmission of VTEC in a substantial proportion of episodes of childhood HUS. PMID- 8432329 TI - Detection of Cowdria ruminantium by means of a DNA probe, pCS20 in infected bont ticks, Amblyomma hebraeum, the major vector of heartwater in southern Africa. AB - A DNA probe, pCS20, previously described for use in detection of Cowdria ruminantium infections in Amblyomma variegatum (the principal vector of heartwater) hybridized with C. ruminantium DNA in organs of laboratory-infected A. hebraeum adult ticks (the major southern African vector of heartwater). The probe hybridized with C. ruminantium DNA in 46/49 midguts from male ticks and 26/29 from females, thus indicating infection. Corresponding salivary glands were less heavily infected, but infections were more numerous in glands from males. Infection in ticks was confirmed by transmission of the disease to susceptible goats. The probe did not hybridize with DNA from uninfected ticks or with DNA from a spotted fever group rickettsia commonly associated with A. hebraeum in Zimbabwe. The C. ruminantium specific pCS20 DNA probe can be applied to determine accurately the infection rates in the two major vectors of heartwater and the risk of exposure of ruminants in endemic areas. PMID- 8432330 TI - Chemical modification of alpha crystallin. AB - Calf lens alpha-crystallin was isolated and the lysine residues were extensively modified with a variety of chemical agents. The effect of these modifications on elastase inhibitor activity, apparent molecular size, antibody reactivity and solubility were determined. The addition of either a methyl group or a threose residue did not alter the charge on the lysine residues and had little or no effect on either inhibitor activity or apparent molecular size. The introduction of a negative charge by either carboxymethylation or citraconylation caused a marked decrease in size and an almost complete loss of inhibitor activity. The introduction of a hydrophobic residue by reaction with either a trinitrobenzenesulfonic acid or Bolton Hunter reagent caused a slight increase in size, but a 70% increase in elastase inhibitor activity. Reaction with fluorescamine resulted in the dissociation of alpha-crystallin in a 200-kDa species, yet caused a two to four-fold increase in elastase inhibitor activity, which was similar to the activity of the water-insoluble fraction isolated from aged human lens and cataract. Several of these modified alpha-crystallins were compared for reactivity with a polyclonal alpha-crystallin antiserum using a quantitative slot blot assay. Charge neutral modifications resulted in a two to three-fold loss of antibody recognition, whereas the other preparations showed an almost complete loss of antigenic activity. None of the modifications caused the alpha-crystallin to precipitate at higher salt concentrations (0.3 M) with the exception of threose which caused a 30% decrease in soluble protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8432331 TI - The altricial pigeon is born blind with a transient glycogen cataract. AB - The lens nucleus of altricial birds contains a large amount of glycogen. It is not known why glycogen in such concentration does not cause a trace of lens opalescence. Here we report that the altricial pigeon is born with a dense nuclear opacity; this opacity has practically disappeared by 4 weeks of age. Thin section electron microscopy revealed that the opacity was specifically associated with an enormous number of large glycogen aggregates in nuclear fiber cells. These aggregates of various sizes (up to approximately 5 microns) were composed of smaller individual 35-nm beta glycogen particles. In contrast, glycogen aggregates were not seen in nuclear fiber cells of all transparent older lenses. The glycogen aggregates have gradually dissociated into a homogeneous distribution of individual beta particles in the entire cytoplasm of nuclear fibers which accompanies the development of lens transparency. This study suggests that an extensive accumulation of glycogen aggregates in the lens nucleus is the cause of light scattering and opacification. The transparency of the altricial pigeon lens during normal development is therefore regulated by two different forms of glycogen. Precocial birds such as chick have no lens glycogen, therefore never develop a glycogen cataract and have excellent visual acuity upon hatching. PMID- 8432332 TI - Efflux and hydrolysis of phosphorylethanolamine and phosphorylcholine in stressed cultured rat lenses. AB - Phosphorylcholine (P-choline), and phosphorylethanolamine (P-ethanolamine) are among the organic phosphate compounds that decrease in concentration in some cataracts and in lenses that have been subjected to cataractogenic osmotic or oxidative stresses. Decreases in the lenticular concentrations of these compounds could be caused by decreased synthesis, increased utilization or hydrolysis, or increased efflux, or by a combination of these mechanisms. To distinguish between these possibilities, the P-choline and P-ethanolamine pools of intact cultured rat lenses were radiolabeled with [3H]choline or [3H]ethanolamine, and the lenses were then subjected to oxidative or osmotic stress. The efflux and hydrolysis of P-[3H]choline and P-[3H]ethanolamine were then followed for up to 48 hr. Osmotic stress induced by incubation with 30 mM xylose caused increased P-choline and P ethanolamine efflux from the lenses, but had little effect on the rate of hydrolysis of these compounds. For example, xylose-treated lenses lost 26% of their initial P-[3H]ethanolamine content into the medium during a 24 hr incubation, compared with only 6% for control lenses. Oxidative stress from singlet oxygen (generated by rose bengal and light) also increased lenticular P choline efflux three to four-fold, with minimal effects on hydrolysis, and the increased efflux was accompanied by a decrease in the P-choline concentration. Permeability increases also were observed in lenses oxidatively stressed by H2O2 or by riboflavin and light. These results show that a variety of cataractogenic stresses, both oxidative and osmotic, cause increased permeability of rat lenses to organic phosphate compounds, including P-choline and P-ethanolamine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8432333 TI - Sugar alcohols in the lens epithelium of age-related cataract. AB - We have measured the levels of glucose and sugar alcohols in the lens epithelium of 24 non-diabetic and 21 diabetic patients undergoing extracapsular cataract extraction for age-related cataract. Lens status was assessed preoperatively according to the Lens Opacities Classification System II. In comparison to non diabetics, the lens epithelia of diabetic patients have increased levels of glucose and sorbitol, and lower content of myo-inositol. Both myo-inositol decrease and sorbitol accumulation are strictly related to the fasting blood sugar level. No correlation or trend was detected in diabetic subjects between myo-inositol or sorbitol level and cataract type. In non-diabetic patients nuclear opacification was associated with a significant increase of myo-inositol level in lens epithelium. PMID- 8432334 TI - A simple technique to determine glutathione (GSH) levels and synthesis in ocular tissues as GSH-bimane adduct: application to normal and galactosemic guinea-pigs. AB - A fluorimetric technique previously described for other tissues has been applied to determine levels of glutathione and its synthetic rates in ocular tissues of Hartley guinea-pigs. Monochlorobimane forms a stable, fluorescent adduct with glutathione in a reaction catalyzed by glutathione-S-transferase. The fluorescent signal recorded over time is directly proportional to the synthetic rate of glutathione. Lens, cornea and retina were homogenized and cytosolic fractions dialyzed overnight to deplete endogeneous glutathione. Glutathione synthetic rates were determined from a mixture of glutathione precursors and co-factors, viz. cysteine+dithiothreitol, glutamate+glycine, ATP and Mg++ in the presence of monochlorobimane. The mixture was supplemented with glutathione-S-transferase to catalyze the formation of the fluorescent adduct. Glutathione synthetic rates were determined in the absence and presence of buthionine sulfoximine, an inhibitor of gamma-glutamyl cysteine synthetase. The difference in fluorescence change over time in the presence and absence of buthionine sulfoximine was used to estimate glutathione synthesis. Basal levels of glutathione in pre-dialyzed cytosolic fractions of the lens, cornea, and retina were 21.8 +/- 2.2, 36.5 +/- 4.1 and 38.6 +/- 2.8 nmol mg-1 protein, respectively. The maximal glutathione synthetic rates in these tissues were 0.52 +/- 0.04, 2.25 +/- 0.67 and 3.35 +/- 0.65 nmol min-1 mg-1 protein, respectively. When gamma-glutamyl cysteine is used as a precursor instead of cysteine, the glutathione synthetase activities from lenses and retinas were 0.19 +/- 0.08 and 1.54 +/- 0.76 nmol-1 min mg-1 protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8432335 TI - X-ray microanalysis of ocular melanin in pigs maintained on normal and low zinc diets. AB - Retinal-choroidal tissues were collected from older sows that were fed either control (100% Zn), intermediate zinc (59% Zn) or low zinc (21% Zn) diets for a 6 month period. The tissues were prepared for elemental energy dispersive X-ray analysis and examined by scanning transmission electron microscopy. Melanosomes of the retinal pigment epithelium and choroidal melanocytes were specifically analysed. The elemental spectra of a specific type of melanosome within a sample region were consistently similar. The elemental spectra of choroidal melanosomes differed slightly from that of RPE melanosomes, having greater levels of calcium, iron and zinc. Changes of the elemental content of both types of melanosomes were observed in the animals that were maintained on low zinc nutrition. Iron and zinc decreased in level, while copper increased. Calcium decreased in the RPE melanosomes of intermediate and low zinc diet animals. However, calcium only decreased in choroidal melanosomes of the low zinc-fed sows, having increased substantially in the intermediate zinc-fed group. Abnormal melanosomes were concomitantly seen in the melanocytes of both the intermediate and low zinc groups. PMID- 8432336 TI - Genetic control of ocular morphogenesis: defective lens development associated with ocular anomalies in C57BL/6 mice. AB - Congenital ocular defects, including microphthalmia, anophthalmia and cataracts appear in a small proportion (5-15%) of the C57BL/6 inbred strain of laboratory mice. Previous work from this laboratory utilizing C57BL/6 in equilibrium with DBA/2 allophenic (mosaic) mice suggested that the underlying cause of these defects may be a deficiency in C57BL/6 lens development. In these C57BL/6 in equilibrium with DBA/2 allophenic animals, the major proportion of the lens cells were of the DBA/2 strain, in contrast to the other ocular and non-ocular tissues examined where no strain-specific competition was evident. Results presented here reinforce the notion that C57BL/6 lens cells are developmentally retarded. In allophenic combination with another strain, A/J, cells of the C57BL/6 strain were, again, markedly underrepresented in the mosaic lens, whereas no such genotypic specificity was evident in any of the other ocular and non-ocular tissues. Thus, the previous observation of a C57BL/6 deficiency in mosaic lens is more likely a consequence of low C57BL/6 competitiveness rather than some peculiar hyperactivity of the cells of the partner strains. Histological examination of C57BL/6, DBA/2 and A/J pure strain embryos indicated marked differences in the lens development of C57BL/6 embryos compared to the other two strains. For the first 3 days after lens invagination, the cross-sectional areas of DBA/2 lenses were two- to three-fold larger than those of C57BL/6 lenses at comparable stages of development, whereas no comparable difference was noted in the optic cup development in these two strains. This leads to a much higher lens/optic cup size ratio in DBA/2 embryos than C57BL/6 embryos. Scanning electron microscopy also revealed that lens invagination is much less extensive in the C57BL/6 embryos than the A/J embryos. The smaller C57BL/6 lens vesicle also remains deeper in the optic cup than those of the DBA/2 or A/J embryos of comparable developmental age. This is likely to result in the occasional complete envelopment of the entire lens vesicle by the optic cup and lead to arrested ocular development. PMID- 8432337 TI - Amelioration of retinal photic injury by a combination of flunarizine and dimethylthiourea. AB - Free radical scavengers and a calcium overload blocker have been demonstrated separately to ameliorate light-induced retinal degeneration, suggesting that both free radical formation and increased intracellular calcium levels are involved in the pathologic changes of this disease process. To understand the relationship between these two mechanisms, we studied the ameliorative effects of combined treatment with flunarizine and dimethylthiourea as well as individual treatment with either drug in a rat model of light-induced retinal degeneration. At 6 hr and 6 and 14 days after light exposure, morphologic and morphometric studies of the retinas from the rats receiving the combined treatment demonstrated better preserved retinal pigment epithelial cells, photoreceptor elements, and nuclei than did retinas from rats receiving treatment with either flunarizine or dimethylthiourea alone. Rhodopsin level measurements at 6 and 14 days further substantiated the results of the protective effects on the photoreceptor outer segments. Because we used a saturating dose for dimethylthiourea, the enhanced ameliorative effect of the combination treatment suggested that free radical formation and elevated intracellular calcium levels were two separate mechanisms in light-induced retinal degeneration. PMID- 8432338 TI - Correlative study of the morphology and central connections of ipsilaterally projecting retinal ganglion cells in the albino rat. AB - Injection of Evans Blue (EB) and 4',6-diamidino-2-phenylindole dihydrochloride (DAPI), fluorescent dyes, into the dorsal nucleus of the lateral geniculate body (dLGN) and the ipsilateral superior colliculus (SC) of albino rats, retrogradely labelled retinal ganglion cells (RGCs). We classified these cells into three categories: (1) double-labelled, geniculate and collicular-projecting RGCs; (2) single-labelled, geniculate-projecting RGCs; and (3) single-labelled, collicular projecting RGCs. Cell soma sizes were measured and the soma size histogram of each category was compared with the others as well as with that of the corresponding category in the contralateral retina. The mean soma size of the ipsilaterally projecting double-labelled RGCs was larger, and their soma size histogram was significantly different in comparison with those of the other two categories. On the contralateral side, the mean soma size of the RGCs labelled only from the SC was smaller, and also their soma size histogram was significantly different from those of the other two categories. On comparing both sides, only the ipsilaterally-projecting double-labelled cells had a significantly different soma size histogram and larger soma size. PMID- 8432339 TI - Oxygen free radicals adversely affect the regulation of vascular tone by nitric oxide in the rabbit retina under high intraocular pressure. AB - Flash electroretinograms (ERG) were recorded in the rabbit eye submitted to high intraocular pressure (HIOP) induced by the suction-cup method. When intraocular pressure rose to 100 mmHg, ERG was suppressed but rapidly recovered even under HIOP when animals were pre-treated either intravitreously with a nitric oxide donor, sodium nitroprusside, or intravenously with free radical scavengers, superoxide dismutase (SOD)+catalase. In contrast, injection of a nitric oxide synthesis inhibitor, nitro-L-arginine, into the vitreous cavity inhibited the protective effect of SOD+catalase during HIOP-induced ERG extinction. These results suggest that nitric oxide could play a role in the regulation of ocular vessel tone and that severe ischemia can impede this effect through oxygen derived free radical generation. PMID- 8432340 TI - Developmental change of distribution of beta-galactoside alpha 2,6 sialyltransferase mRNA in rat retina. AB - A substantial change in the glycoconjugates of the rat interphotoreceptor matrix (IPM) has recently been shown to occur between post-natal day (P) 14 and P16 in rat retinas using lectin histochemistry. This suggests that the sialic acid content on the terminus of N-glycoside linked carbohydrate chains of the IPM increases between P14 and P16. In the present study, to test this hypothesis, we examined the developmental change of distribution of beta-galactoside alpha 2,6 sialyltransferase mRNA in rat retina using in situ hybridization histochemistry. C-DNA of rat alpha 2,6-sialyltransferase was isolated by PCR and cloned into the polylinker site of Bluescript KS (+). Antisense and sense RNA probes were labelled with digoxigenin-UTP by in vitro transcription with T3 and T7 RNA polymerases, respectively. Paraffin sections of rat retinas between P12 and P42 were incubated with the antisense or sense RNA probes. Specific labelling with the antisense probe was observed strongly in the cytoplasm of all ganglion cells and weakly in partial cells of the inner nuclear layers throughout the examined postnatal days. A remarkable change was observed in the photoreceptor cells between P14 and P16. Hybridization signals of the outer nuclear layer was observed from P14, while those of the inner segments were detected on P16 and thereafter. The alpha 2,6-sialyltransferase newly expressed in the inner segments on P16 appears to sialylate the Gal beta 1, 4GlcNAc residue of N-glycosidically linked glycoconjugates of the IPM, resulting in the change of lectin staining profiles. PMID- 8432341 TI - Normalization of striatal proenkephalin and preprotachykinin mRNA expression by fetal substantia nigra grafts. AB - The expression of striatal proenkephalin and preprotachykinin mRNA was studied in Wistar rats following unilateral injections of 6-hydroxydopamine into the nigrostriatal pathway and after grafting dopaminergic fetal cell suspensions into the dopamine-depleted striatum. Striatal dopaminergic deafferentation resulted in an amphetamine-induced rotational asymmetry, an increase in ipsilateral striatal proenkephalin mRNA, and a decrease in preprotachykinin mRNA expression. Twelve months following grafting, proenkephalin and preprotachykinin mRNA returned to near-normal levels in contrast to control nongrafted lesioned animals. In addition, reversal of the rotational asymmetry was routinely observed. This study has demonstrated long-term graft-induced functional recovery coincident with normalization of striatal proenkephalin and preprotachykinin mRNA expression. PMID- 8432342 TI - Functional alterations induced by prenatal malnutrition in callosal connections and interhemispheric asymmetry as revealed by transcallosal and visual evoked responses in the rat. AB - It is known that nutritional restriction during gestation affects the growth of the corpus callosum. The present study was designed to evaluate whether prenatal malnutrition may alter, in the rat, the normal pattern of functional callosal interhemispheric connections of the visual cortex. Since callosal development has been associated with brain lateralization, the effect of malnutrition during gestation on the normal asymmetry of visual cortical evoked responses was also studied. Prenatal malnutrition was induced by restricting food consumption by pregnant rats (10 g daily) from Day 8 post-conception to parturition. Results of experiments performed on 45- to 50-day-old offspring showed that the starvation treatment (i) reduced both the peak-to-peak amplitude and the extent of the projecting field of transcallosal evoked responses, and (ii) abolished the normal brain interhemispheric asymmetry of visual evoked responses. These effects are discussed in relationship to regressive events occurring during synaptogenesis, which are known to play key roles in establishing the adult structure and functional properties of the corpus callosum. PMID- 8432343 TI - Expression of c-fos mRNA following seizures evoked from an epileptogenic site in the deep prepiriform cortex: regional distribution in brain as shown by in situ hybridization. AB - Using in situ hybridization histochemistry for the detection of c-fos mRNA, we examined the pathways activated by seizures evoked by a focal application of bicuculline into a highly discrete epileptogenic site in the deep prepiriform cortex, the area tempestas (AT). Thirty minutes after the initiation of limbic motor seizures evoked by bicuculline in AT, a marked increase in c-fos mRNA was detected in the hippocampal formation, amygdala, olfactory bulb, piriform cortex, and entorhinal cortex. The increase of c-fos mRNA was strictly dependent upon the infusion of the drug in AT. Infusions of bicuculline in the same dose outside the AT did not increase c-fos mRNA levels. The extent to which the mapping pattern of c-fos mRNA expression was specific to limbic seizures was evaluated by examining another focally evoked seizure model involving the application of bicuculline bilaterally into the inferior colliculus. The absence of any detectable c-fos induction in the limbic system after explosive running-bouncing clonic seizures evoked by bicuculline injected into the inferior colliculus indicates that the pattern of activation that we found in the AT-evoked seizure model is not common to all forms of convulsive activity. Furthermore these observations suggest that the pattern of activation we have observed is seizure dependent and not stress induced. Our results indicate that c-fos mRNA expression is useful in the functional mapping of pathways involved in seizure propagation and that the anatomic pattern of activation is selectively related to the type of seizure evoked. PMID- 8432344 TI - Atrophy and degeneration of ganglion cells in central retina following loss of postsynaptic target neurons in the dorsal lateral geniculate nucleus of the adult cat. AB - Selective degeneration of neurons in the dorsal lateral geniculate nucleus (dLGN) of the adult cat was produced by in situ injection of kainic acid. This rapid degeneration mimics the loss of lateral geniculate neurons seen after neonatal visual cortex ablation. Following survivals of 2, 4, or 6 months, the geniculate was injected with horseradish peroxidase (HRP) and the retinas were examined for the presence of retrogradely labeled, as well as unlabeled, cells. Total ganglion cell density in central nasal retina was not different from that of controls at 2 or 4 months, but by 6 months had decreased to 68% of control values. The proportion of cells labeled with HRP did not change at 2 months, but decreased from 84% in controls to less than 1% by 4 months, and none were labeled at 6 months. Surviving ganglion cells in central retina showed atrophy of the cell body, a finding not apparent in data from the retinal periphery. Shrinkage occurred in the few cells labeled with HRP surviving at 4 months, as well as among the unlabeled cells surviving at 4 and 6 months. These results show that the survival of central retinal ganglion cells in the cat continues to depend on intact target neurons beyond the period of development. Mature ganglion cells in central retina respond to loss of appropriate targets first by axon terminal retraction and then by atrophy and cell death. However, when compared to the response of cells located in far peripheral retina following dLGN neuron loss, central ganglion cells take longer to undergo axonal retraction and a greater proportion of the central ganglion cells, although atrophied, survive after 6 months. PMID- 8432345 TI - Retrograde transneuronal degeneration in a basal ganglia target, the lateral spiriform nucleus, induced by anterograde transneuronal degeneration following eye removal in the chicken. AB - The chicken lateral spiriform nucleus (Spl) receives its major input from the paleostriatum primitivum of the forebrain, projects almost exclusively upon the optic tectum, but receives no projections from the tectum. In the present study we show that not only do tectal ablations reduce the volume of the Spl, the cross sectional area, and the number of Spl neurons, but eye removal also produces a statistically significant reduction in Spl volume, cross-sectional area, and neuron number. Because the retina does not project upon the Spl directly, and because both the retina and the Spl project upon the optic tectum, we propose that the retina produces its effects upon the Spl by an anterograde transneuronally induced retrograde transneuronal mechanism. PMID- 8432346 TI - Selective vulnerability and early progression of hippocampal CA1 pyramidal cell degeneration and GFAP-positive astrocyte reactivity in the rat four-vessel occlusion model of transient global ischemia. AB - Selective, delayed-onset vulnerability of hippocampal CA1 pyramidal cells has been reported as a unique phenomenon in man and the rat four-vessel occlusion (4 VO) model of global ischemia. This has become of great interest for clarification of CA1 pathophysiology and pharmacological intervention after global ischemia. Studies of pathophysiology and pharmacotherapy appear to be impeded by variability in specific criteria and duration of 4-VO ischemia for producing selective CA1 and differential CA1-CA3 damage. The goals of this study were to: (1) develop specific criteria for 4-VO ischemia to ensure selective, bilaterally symmetrical CA1 pyramidal cell damage, (2) examine the effects of 15 min of ischemia on concomitant CA1 cell necrosis and presence of remaining and/or "viable" neurons postischemia, (3) compare 15 and 30 min of ischemia on differential vulnerability of CA1-CA3 subfields, and (4) evaluate the effects of 15 min of ischemia on CA1 pyramidal cell necrosis and glial fibrillary acidic protein (GFAP)-positive astrocyte reactivity in CA1. After 15 min of ischemia, hippocampal pyramidal cell damage was well delineated, with CA1 severely damaged, but leaving CA3 virtually intact. In contrast, 30 min of ischemia produced severe CA1 and less severe CA3 necrosis. Histological evaluations across Days 1, 3, 6, and 14 indicated a significant delayed onset of CA1-CA3 cell necrosis by Day 3. Counting of remaining cells indicated a detectable loss of some large pyramidal neurons even 1 day after ischemia. Compared to controls, there was a differential increase in GFAP-positive astrocytes in CA1-CA3 after ischemia. The results provided quantitative data on the effects of specific 4-VO criteria and durations on: (1) selective CA1 cell necrosis, (2) differential CA1-CA3 cell vulnerability, (3) presence of postischemic remaining and/or viable neurons, and (4) prospect of a "therapeutic window" for pharmacological treatment of CA1 neuronal injury. PMID- 8432347 TI - Interaction of hypoxia and hypothermia on dorsal column conduction in adult rat spinal cord in vitro. AB - Trauma reduces both action potential amplitudes and conduction velocities, as well as the ability of axons to follow high-frequency stimulation, in spinal cord dorsal columns. Since white matter blood flow falls after spinal cord injury, hypoxia may play a role in post-traumatic axonal dysfunction. We examined the effects of hypoxia on action potential conduction in isolated adult rat dorsal columns under normothermic (37 degrees C) and hypothermic (25 degrees C) conditions. After stabilization in oxygenated Ringer's solution (95% O2 and 5% CO2), the isolated dorsal columns were superfused with hypoxic Ringer's solution (95% N2 and 5% CO2) for 120 min, followed by 90 min of reoxygenation. At 37 degrees C, hypoxia markedly depressed response amplitudes to 25 +/- 9% (mean +/- SEM, n = 7) of prehypoxic levels but paradoxically increased population conduction velocity to 133 +/- 6%. Reoxygenation restored response amplitudes to 57 +/- 11% and population conduction velocities returned to prehypoxic levels. At 25 degrees C, the dorsal columns were significantly less sensitive to hypoxia. Response amplitudes fell to 50 +/- 6% (n = 7) after hypoxia and recovered to 77 +/- 6% after reoxygenation. Normothermic dorsal columns responded to 500-Hz stimuli with minimal amplitude changes before (-9 +/- 3%, n = 7) and after hypoxia (-13 +/- 2%). In hypothermic preparations, 500-Hz stimulation depressed response amplitudes before (-40 +/- 8%, n = 7) and after hypoxia (-56 +/- 8%); they were not significantly different from each other.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8432348 TI - Temporal and spatial patterns of expression of c-fos, zif/268, c-jun and jun-B mRNAs in rat brain following seizures evoked focally from the deep prepiriform cortex. AB - Using in situ hybridization, we previously investigated (17) the regional pattern of c-fos mRNA increases in the brain following convulsive seizures elicited from a highly circumscribed epileptogenic site located in the deep prepiriform cortex. In this paper, we focus on the hippocampus and examine mRNAs encoding other immediate early genes (IEGs), namely c-jun, jun-B, and zif/268, for changes following the focally evoked seizures. Although the anatomic distribution of increases in each IEG mRNA was qualitatively comparable, the temporal analysis indicated that increases in zif/268 mRNA appeared prior to the other genes studied. Each of the mRNAs reached a maximum increase by 30 min and declined to basal levels within 3 h following seizure initiation. The data indicate that these four IEGs respond in a coordinated fashion to propagated seizure activity with increases in mRNA and, furthermore, that increased expression of all four genes appears to occur in the same cell types in the hippocampus. PMID- 8432349 TI - Altered gene expression after optic nerve transection: reduced neurofilament expression as a general response to axonal injury. AB - Previous studies have shown that axonal injury (axotomy) in neurons of the mammalian peripheral nervous system (PNS) results in a recapitulation of the developmental program for cytoskeletal gene expression; these changes include the increased expression of a developmentally regulated isotype of beta-tubulin (class II) and reduced neurofilament (NF) expression. In the present study we examined the abundance of mRNAs encoding the low-molecular-weight NF protein (NF L) and class II beta-tubulin in RNA purified from the retinae of newborn rats, from the retinae of adult rats at 2, 7, and 14 days after intracranial transection of the ipsilateral optic nerve, and from contralateral control retinae. In order to facilitate comparison with representative PNS neurons, parallel analyses were carried out in axotomized dorsal root ganglion (DRG) sensory neurons. Since NF-L and class II beta-tubulin are neuron-specific proteins, axotomy-induced alterations in the levels of retinal mRNAs encoding these proteins largely reflect corresponding changes in expression by retinal ganglion cell neurons. Comparison of retinal RNA from newborn and adult (70-day old) animals demonstrated a postnatal increase in NF-L and a decline in class II beta-tubulin mRNAs comparable to those previously described in DRG neurons. Reductions in NF-L mRNA levels were noted in retina at 2, 7, and 14 days after axotomy and in DRG neurons at 7 and 14 days after axotomy. The abundance of class II beta-tubulin mRNAs increased after axotomy in DRG neurons, but not in retina.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8432350 TI - Neurotropism of nerve growth factor for adult rat septal cholinergic axons in vivo. AB - Nerve growth factor (NGF) can induce sprouting of axotomized adult rat medial septum cholinergic neurons and promote their regeneration into septohippocampal nerve grafts and hippocampal formation. This study investigated the potential neurotropic (chemotactic/attracting) action of NGF in the adult rat cholinergic septohippocampal regeneration model. (i) Some animals received sciatic nerve grafts between the disconnected septum and hippocampal formations on each side. A 4-week infusion with NGF into the rostral portion of the lateral ventricle induced sprouting of cholinergic fibers in the dorsolateral septum with a gradient toward the lateral ventricle. However, the number of cholinergic axons entering the nerve bridge was only one-third that observed in vehicle-infused animals, suggesting that NGF had diverted many of the regrowing axons away from the nerve toward the ventricle. (ii) In animals implanted with nerves for 2 weeks and concurrently infused with NGF into the fornix, proximal to the lesion and grafts, cholinergic sprouting occurred in the mediodorsal septum, i.e., was oriented toward the infused fornix. Essentially no fibers had entered the nerve bridge, suggesting that all regrowing fibers had remained near the NGF source. (iii) When animals with a unilateral fimbria-fornix transection (but no nerve graft) were infused with NGF into the lateral ventricle on the opposite side, cholinergic sprouting was oriented toward the midline of the septum. (iv) Infusion of low doses of NGF directly into the (lesioned) septum induced a sprouting response localized around the infusion site. (v) No sprouting occurred when intraventricular NGF infusion was applied to normal (nonlesioned) animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8432351 TI - Excitotoxin lesions in primates as a model for Huntington's disease: histopathologic and neurochemical characterization. AB - Excitotoxin lesions induced by quinolinic acid (QA) were made unilaterally in the caudate nucleus and putamen of 12 rhesus monkeys. Both acute (2-3 weeks) and chronic (4-6 months) effects were evaluated. Excitotoxin striatal lesions were characterized by a central zone of intense astrogliosis and marked neuronal depletion, which was surrounded by a transition zone in which there was partial neuronal sparing throughout the entire lesioned side. Immunocytochemical and enzyme histochemical markers for both large and medium-sized aspiny- and spiny striatal neurons clearly demonstrated a selective pattern of neuronal vulnerability to the excitotoxic effects of QA within lesioned striata. Medium sized spiny neurons containing calbindin Dk28, enkephalin, and substance P were disproportionately lost, while aspiny neuronal subpopulations containing NADPH diaphorase (NADPH-d) and choline acetyltransferase activity (ChAT) were relatively spared. Combined labeling by NADPH-d enzyme histochemistry and Nissl staining, as well as NADPH-d histochemistry and calbindin Dk28 immunocytochemistry, demonstrated significant increases in the ratio of aspiny to spiny neurons within the lesioned striata. Neurochemical measurements confirmed a loss of GABA and substance P-like immunoreactivity yet no significant depletion of somatostatin-like immunoreactivity, neuropeptide Y-like immunoreactivity, or ChAT were seen. The striatal patch-matrix pattern persisted, as demonstrated by acetylcholinesterase activity. The pattern was altered, however, in the chronic animals, such that the matrix zone was significantly reduced, while the total area of patches remained within normal limits. Ultrastructural analysis confirmed axon sparing lesions with neuronal loss and astrogliosis. Pretreatment of 3 monkeys with MK-801, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist, blocked striatal QA neurotoxicity. The present results provide an experimental primate model which closely resembles the neuropathologic and neurochemical features of Huntington's disease. These findings further strengthen the possibility that an NMDA receptor-mediated excitotoxic process plays a role in the pathogenesis of this disorder. PMID- 8432352 TI - Differential actions of neurotrophins in the locus coeruleus and basal forebrain. AB - The neurotrophin gene family, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and NT-4/NT-5, supports the survival of distinct peripheral neurons, however, actions upon central neurons are relatively undefined. In this study we have compared different neurotrophins in the regulation of neuronal survival and function using dissociated embryonic cell cultures from two brain regions, the basal forebrain (BF) and locus coeruleus (LC). In the BF, NGF increased choline acetyl transferase (ChAT) activity, but did not influence cholinergic cell survival. In contrast to NGF, BDNF, NT-3, and the novel neurotrophin, NT-4, all increased ChAT activity and cholinergic cell survival. We also examined embryonic LC neurons in culture. LC neurons are unresponsive to NGF. In contrast, NT-3 and NT-4 elicited significant increases in survival of noradrenergic LC neurons, the first demonstration of trophic effects in this critical brain region. Identification of factors supporting coeruleal and basal forebrain neuronal survival may provide insight into mechanisms mediating degeneration of these disparate structures in clinical disorders. PMID- 8432353 TI - Pre- and postsynaptic neurotoxic effects of dopamine demonstrated by intrastriatal injection. AB - Considerable evidence indicates that dopamine (DA) may play a neurotoxic role in brain in certain pathologic circumstances. To investigate this issue, dopamine (1000 nmol/1 microliter) was directly injected into the striatum of anesthetized Sprague-Dawley rats. Control animals received equal-volume injections of gamma aminobutyric acid (GABA) or NaCl at identical concentrations (diluted in distilled H2O, pH 7.0-7.7). Brains were removed 7 to 9 days later and frozen or fixed and sectioned for histologic and autoradiographic analysis. Dopamine injection resulted in a small-volume (3.3-mm3) lesion in comparison to control GABA and NaCl injections which produced only a needle track < 0.6 mm3 in volume (P < 0.01). Dose dependency of DA toxicity was demonstrated, with substantial parenchymal damage requiring an injection of 500 nmol/1 microliter. Within the lesion, marked neuronal loss, macrophage invasion, and capillary and glial proliferation were present. Acetylcholinesterase staining and D1 receptor binding were markedly reduced as well. [3H]RO5-4864 binding to peripheral benzodiazepine receptors (on astrocytes) was increased in the periphery of the lesion. The binding of 1-[3H]benzo[b]cyclohexylthiophenylpiperidine to dopamine uptake sites was also reduced, but over a wider striatal area in comparison to local parenchymal damage. Prior interruption of the dopaminergic nigrostriatal pathway (by injection of 6-hydroxydopamine) appeared to potentiate the toxicity of intrastriatal dopamine injection. The findings indicate that local injection of dopamine produces both post- and presynaptic damage to nigrostriatal structures, and support the contention that dopamine may act as a low-potency neurotoxin. PMID- 8432354 TI - The microstructure of cortical neuropil before and after decompression in experimental infantile hydrocephalus. AB - Hydrocephalus is a common clinical disorder and responsible for many pediatric neurological deficits. Relatively little is known about the cellular mechanisms of this disorder and less is known about reconstitution of connectivity following ventricular shunt procedures. In the present studies experimental infantile hydrocephalus produced by kaolin injection was studied in a neonate kitten model. The neuropil of the cerebral cortex was examined in hydrocephalic animals and animals which received a ventriculoperitoneal shunt to reduce ventriculomegaly. The brains were processed for Golgi silver impregnation and electron microscopy to study the detailed dendritic and synaptic architecture. The periventricular region of the hydrocephalic animals exhibited increased extracellular space and signs of neuronal degeneration. Components of the deep neuropil (laminae V-VI) were in disarray and surrounded by edematous extracellular spaces. The superficial neuropil (laminae I-IV), in contrast, appeared intact, but detailed examination showed indications of dendritic degeneration. Shunt procedures successfully restored the cortical mantle to near normal thickness. However, Golgi light microscopy and electron microscopy revealed that dendritic appendage morphology was altered. The results are discussed in regard to development of neuronal connectivity following shunt procedures. PMID- 8432355 TI - Functional projection of regenerated rat sural nerve axons to the hindpaw skin after sciatic nerve lesions. AB - The functional regeneration of polymodal C-fibers and low-threshold mechanoreceptive axons in the rat sural nerve was evaluated 3 months after a sciatic nerve crush lesion or neurotomy and suture. The distribution of polymodal C-fibers was tested through stimulation-induced extravasation of Evans blue albumin in the foot skin. As judged from the area of stained skin, the polymodal sural C-fibers regenerated efficiently after both lesion types. In regenerates, though, the borders of the stained domain were less clearly defined than in controls, and there were minor territorial abnormalities. The Evans blue-stained area on the unoperated side in neurotomy/suture cases was significantly smaller than in normal control animals. The area covered by low-threshold mechanoreceptors in the foot skin was tested through gentle mechanical stimulation with a blunt probe and electrophysiological recording from the sural nerve. In regenerates the foot skin area covered by functional low-threshold mechanoreceptors turned out to be reduced on the operated side compared to controls, particularly after neurotomy/suture. We conclude that sural nerve regeneration is accompanied by a spatially more complete reestablishment of functional C-fiber-related cutaneous polymodal nociceptors than of functional cutaneous low-threshold mechanoreceptors. PMID- 8432356 TI - Retrograde horseradish peroxidase transport in motor axons after Nd:YAG laser irradiation of the tibial nerve in rats. AB - We have recently demonstrated that the number of small sensory neurons of the A delta- and C-fiber group in lumbar dorsal root ganglia labeled with horseradish peroxidase (HRP) is selectively decreased 7 days after Nd:YAG laser irradiation of the tibial nerve in the rat. In contrast, the number of large diameter sensory neurons was not affected by laser application. In an attempt to clarify the fate of motoneurons after laser irradiation of their peripheral axons, the numbers of lumbar motoneurons retrogradely labeled with HRP 7 days after Nd:YAG laser irradiation of the tibial nerve have been determined in rats. Our results show that the number of HRP-labeled motoneurons in lumbar segments L6 to L3 is not altered to a significant extent after laser irradiation of their peripheral axons (laser-treated side, 767 +/- 10 cells vs control side, 808 +/- 19; n = 5, mean +/ SEM). In addition, no difference was detected in the mean value or the distribution of soma cross-sectional areas of labeled motoneurons on the laser treated side and the control side. Specifically, the numbers of HRP-labeled small diameter motoneurons, which are presumably gamma in type and have a conduction velocity similar to sensory neurons of the A-delta group, were not affected by laser application. Possible mechanisms of the differential vulnerability of sensory neurons as compared to motoneurons of similar size are discussed. PMID- 8432357 TI - Methods to assess the development and recovery of locomotor function after spinal cord injury in rats. AB - The ability to assess recovery of function after spinal cord injury is a very important part of spinal cord injury research. Recent progress has been made in a number of avenues of treatment designed to ameliorate the consequences of spinal cord injury and enhance recovery of function. This potential for intervention to modify the sequellae of spinal cord injury requires stringent criteria for methods used to evaluate the effects of injury and subsequent recovery of function. Methods which rely on composite ratings of an animal's overall performance, while appropriate for screening groups of animals with spinal cord injury, are not sufficient to demonstrate whether a particular treatment has had a specific effect on motor function or the degree to which function is affected. We have designed a series of sensitive quantitative methods to assess the recovery of locomotor function in rats. The methods examine specific reflex responses and specific components of motor behavior and are sensitive to subtle differences in the pattern of locomotion and individual limb movements. Several of the tests can be used to assess the development of locomotor function as well as the mature response. Postural reflex testing and locomotor function under conditions of graded difficulty are examined and the motor capacity of individual limbs is assessed. Animals are trained to cross runways, to walk on a treadmill, and to climb onto a platform. The animals' performance is videotaped for subsequent quantitative analysis. The pattern of overground and treadmill locomotion is also examined by footprint analysis. Spinal cord injury alters an animal's reflex responses and deficits are evident in locomotor function. Examples are given of the quantitative measurements obtained from analysis of the animals' performance on each of the tests. No single test is sufficient to assess recovery of function after spinal cord injury. Rather, a combination of tests, each examining particular components of normal and recovered motor function, is required. The methods used to assess recovery of locomotor function are specific, are sensitive, and allow individual limb movements to be isolated. Such specific methods allow one to begin to address the mechanisms underlying recovery of function following spinal cord injury. PMID- 8432358 TI - Nerve growth factor facilitates regeneration across nerve gaps: morphological and behavioral studies in rat sciatic nerve. AB - The rat sciatic nerve does not possess a high potential for regeneration through silastic tubes when the interstump nerve gap is greater than 10 mm. In this study, the effect of NGF treatment on regeneration of the rat sciatic nerve in 10 and 15-mm silastic chambers was compared. In addition, regeneration in 15-mm silastic chambers was compared to regeneration in 15-mm semipermeable chambers. Sections of tubing were implanted and filled with NGF or a control solution of cytochrome C (Cyt. C). Tube implants were removed at various postoperative times and regeneration was assessed histologically and behaviorally. NGF treatment promoted regeneration success rate. It enhanced the initial outgrowth of nonneuronal cells and neuronal fibers into the chamber producing more cellular, organized regenerates. At 2 weeks, in 10-mm chambers, NGF-treated regenerates had fourfold more unmyelinated fibers than controls. At 3 weeks, NGF-treated regenerates possessed threefold more myelinated fibers than controls. After 4 weeks all regenerates had similar numbers of myelinated nerves at the chamber's midpoint. This initial "head start" was sustained peripherally as indicated by the earlier return of sensory function (response to a noxious temperature stimulus) in NGF-treated animals. Finally, regeneration success rate in 15-mm semipermeable tubes is greater than that in 15-mm silastic chambers (NGF and Cyt. C). However, regenerates in silastic chambers possessed twofold more myelinated fibers than regenerates in semipermeable chambers. The positive effects of NGF on neural regeneration and recovery of sensory function provide support for the potential use of NGF in treating peripheral nerve injuries. PMID- 8432359 TI - Lead blocks LTP by an action not at NMDA receptors. AB - Exposure of children to low levels of lead results in a reduction in cognitive ability and a series of behavioral deficits. We have studied the effects of PbCl2 on long-term potentiation (LTP), the best available electrophysiologic model of learning and memory, in a rat piriform cortex brain slice preparation in order to test the hypothesis that lead neurotoxicity is a result of actions on LTP. With changes in the composition of the Krebs-Ringer solution normally used in brain slices, it is possible to keep the Pb2+ in solution at concentrations up to 10 microM. In this concentration range, Pb2+ has no effect on the synaptic response elicited in piriform cortex pyramidal neurons upon stimulation of the lateral olfactory tract. We find that Pb2+ blocks LTP by about 75% at 5 microM and completely at 10 microM. At these concentrations, Pb2+ has no effect on posttetanic potentiation. Since it has been reported that Pb2+ blocks N-methyl-D aspartate (NMDA) responses, and NMDA blockade is known at many sites to block LTP, we studied the effects of Pb2+ on NMDA responses. In the concentration range studied there was no effect of Pb2+ on NMDA responses. The mechanism whereby Pb2+ blocks LTP remains to be determined. While the concentration of Pb2+ found to block LTP in these studies is high relative to concentrations of Pb2+ in blood that are associated with causing cognitive and behavioral effects in children, the sensitivity to Pb2+ may be greater in young animals. PMID- 8432360 TI - Noncompetitive and competitive NMDA antagonists exert anticonvulsant effects by actions on different sites within the neuronal network for audiogenic seizures. AB - Excitant amino acids are implicated in audiogenic seizure (AGS) susceptibility in the genetically epilepsy-prone rat (GEPR). In the present study systemic administration of NMDA receptor antagonists significantly decreased AGS severity in the GEPR. Systemic administration of the competitive NMDA antagonists 3-((+-) 2-carboxypiperazin-4-yl)-propyl-1-phosphonate (CPP) and 2-amino-7 phosphonoheptanoic acid and the non-competitive antagonist dizocilpine (MK-801) were effectively anticonvulsant in the GEPR. The inferior colliculus is the most critical nucleus for AGS initiation in the GEPR and an excitant amino acid is implicated as an important excitatory transmitter in inferior colliculus neurons. Systemically administered CPP significantly reduced inferior colliculus neuronal firing in the normal behaving rat and the GEPR concurrently with blockade of AGS and this effect occurred at nearly all sound intensities tested. Systemic administration of MK-801, while effective in blocking AGS, produced no consistent change in inferior colliculus neuronal firing, which is consistent with its very low potency in blocking AGS with bilateral microinjection into the inferior colliculus. These findings suggest that an important action of competitive, but not noncompetitive, NMDA antagonists is on brain stem auditory nuclei, especially the inferior colliculus, that are critical to AGS. MK-801 appears to exert its anticonvulsant effects in AGS network sites beyond the inferior colliculus. These findings and recent inferior colliculus slice studies suggest that NMDA receptors in inferior colliculus may have quantitatively different properties from those in other brain regions. These differences in NMDA receptor function in inferior colliculus may reflect NMDA receptor heterogeneity observed in binding studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8432361 TI - Involvement of neurons sensitive to angiotensin II in the median preoptic nucleus in the drinking response induced by angiotensin II activation of the subfornical organ in rats. AB - The involvement of neurons sensitive to angiotensin II (ANG II) in the median preoptic nucleus (MnPO) in mediating the drinking response caused by administration of ANG II either directly into the subfornical organ (SFO) or intravenously was examined in the conscious rat. In all rats (n = 16) having correct injector placement in both of these brain sites, injections of ANG II (10(-12) M) into the SFO elicited drinking. Previous injections of saralasin (10( 10) M), a specific ANG II antagonist, but not saline vehicle, into the MnPO significantly attenuated the drinking response to ANG II administration directly into the SFO. Intravenous infusions of ANG II (75 ng/kg) produced a drinking response in 12 of the 16 rats, and the response was significantly reduced by pretreatment with saralasin (10(-10) M), but not by saline, in the SFO. These results show the importance of MnPO neurons responsible for ANG II in mediating the dipsogenic response to ANG II acting at the SFO and suggest that the response may be implicated in angiotensinergic neural circuits from the SFO to the MnPO. PMID- 8432362 TI - The heavy neurofilament protein is expressed in regenerating adult but not embryonic mammalian optic fibers in vitro. AB - Axonal neurofilaments are composed of light (NF-L), medium (NF-M), and heavy (NF H) subunits which are sequentially expressed during axonal development. In retina, NF-L and NF-M appear prenatally, followed postnatally by NF-H which occurs at about the time axons are reaching their target tissue. Phosphorylation of the NF-H protein occurs after it has first appeared in the axon. Phosphorylated NF-H is also downregulated in regenerating peripheral nerves. These observations lead to the hypothesis that NF-H stabilizes axons, thereby inhibiting their ability to grow. We have previously shown that adult mouse retinal ganglion cells (RGCs) can extend neurites in vitro and that these neurites reexpress the developmental protein GAP-43. Here we ask whether the expression of neurofilament proteins in the growing adult RGC axons involves the recapitulation of development. Adult mice which had a priming lesion of the optic nerve and Embryonic Day 15 mouse retinas were explanted onto laminin substrates and grown in culture. After 2-4 days the growing neurites were stained with a battery of monoclonal antibodies against differentially phosphorylated versions of the neurofilament subunits. Both adult and embryonic neurites were highly immunoreactive for NF-L and NF-M. Only the adult neurites stained with antibodies against phosphorylated NF-H. There was no immunoreactivity in the embryonic explants. This indicates that regrowing adult RGC axons maintain their adult cytoskeletal properties and can nevertheless regenerate. PMID- 8432363 TI - A comparison of YM-14673, U-50488H, and nalmefene after spinal cord injury in the rat. AB - A reproducible spinal cord injury model was used to compare the efficacy of three compounds previously shown to improve neurologic recovery after injury in rats: The thyrotropin releasing hormone (TRH) analogue, YM-14673; the specific kappa opioid agonist, U-50488H; and the opioid antagonist, nalmefene, which has increased activity at kappa-receptors. A moderate injury in rats that results in recovery of uncoordinated gross locomotion was made at spinal T9 by rapid displacement (1.1. mm) of the cord. Compounds (or vehicle) were given either by intravenous bolus or by continuous mini-osmotic pump over 7 days, beginning 30 min after the injury as follows: controls (saline), YM-14673 (1 mg/kg bolus), U 50488H (10 mg/kg bolus), U-50488H (0.425 mg/kg/h continuous infusion x 7 days); nalmefene (0.1 mg/kg bolus); and nalmefene (0.021 mg/kg/h continuous infusion x 7 days). Neurologic recovery was assessed for 4 weeks by open-field walking, inclined plane, grid walking, and footprint analysis. The percentage of white matter spared was determined at the lesion epicenter. Only those groups given a bolus of YM14673, U-50488H, and nalmefene had open-field performance better than the scores of controls. Animals that received a bolus of YM-14673 also scored better than controls on the inclined plane and were more likely than controls to recover sufficiently to be tested by both grid walking and footprint analysis. Improved behavioral recovery was not found in groups that received chronic drug infusion. Histology demonstrated significant sparing of white matter for the YM 14673-treated group compared with controls; groups given a U-50488H and nalmefene bolus showed a trend for greater sparing of white matter. The results confirm a beneficial effect for these compounds and suggest that they may be useful in treatment of clinical spinal cord injury. PMID- 8432364 TI - Effect of rat subarachnoid hemorrhage on serotonin innervation of the cerebral ventricular wall and serotonin neurons of the ventral surface of the brain stem: an immunohistochemical study. AB - The effect of subarachnoid hemorrhage on serotonin (5-HT) innervation of the cerebral ventricles and on 5-HT neurons in the ventral surface of the brain stem was studied immunohistochemically in the rat. Subarachnoid hemorrhage (SAH) was induced by injection of autologous arterial blood into the cisterna magna. In normal and sham-operated animals, the entire ependyma of the ventricles was supplied with 5-HT-immunoreactive supraependymal nerves. The ependyma in the dorsal third ventricle received the most dense innervation. 5-HT neurons on the surface of the brain stem were found in the median fissure and on the ventral surface of the pyramidal tract. A marked reduction in supraependymal 5-HT immunostaining was observed in animals sacrificed as early as 6 h post-SAH and this change continued until 14 days and recovered by 28 days following SAH. 5-HT neurons on the ventral surface of the brain stem were visible even in the rat with SAH. The results suggest that SAH caused a transient depletion of 5-HT immunoreactivity in the supraependymal nerves but 5-HT neurons on the ventral surface of the brain stem were unchanged. Depletion of 5-HT immunoreactive nerves on the cerebral ventricular wall might be involved in the pathophysiology after SAH. PMID- 8432365 TI - Explosive autotomy induced by simultaneous dorsal column lesion and limb denervation: a possible model for acute deafferentation pain. AB - We report on a new "explosive" form of self-mutilation behavior (autotomy) characterized by rapid onset (1-2 days), short duration (1-2 days), and unpredictable progression. The possible neural mechanism(s) underlying this novel behavior were examined in rats by combining at varying time intervals one leg denervation with a lesion to the dorsal columns (DC lesion) or to a dorsolateral funiculus (DLF lesion). DC lesion, followed immediately by leg denervation, resulted in explosive autotomy in 62% of the rats and regular autotomy in 25% of the rats. Regular autotomy was characterized by slow onset (2-3 weeks), prolonged duration (2-3 weeks), and stereotyped progression from distal to proximal parts of the leg. DC lesion, followed 1 week later by leg denervation, resulted in regular autotomy in 71% of the rats which was not different from autotomy resulting from denervation alone. DC lesion preceded 1 week earlier by leg denervation resulted in slightly accelerated regular autotomy in 77% of the rats. Simultaneous DC lesion and leg denervation immediately preceded by application of a local anesthetic (4% procaine) for 30 or 60 min to the exposed lumbar spinal cord resulted in regular autotomy in all rats. All rats in a sham group, in which the procaine was replaced by normal saline, exhibited explosive autotomy. DLF lesion, followed immediately by leg denervation, resulted in accelerated regular autotomy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8432366 TI - The role of previous nociceptive input in development of autotomy following cordotomy. AB - Intractable pains have been described after surgical or accidental lesions in the peripheral or central nervous system. The possible contribution of antecedent injury to the appearance of these pains was examined in an animal model for chronic pain which involved observing self-mutilation or autotomy behavior in rats. Various combinations of previous injury, selective spinal cut, and peripheral denervation were carried out on rats. Injuries ranged from mild to moderate and were produced by nociceptive stimuli from formaldehyde injection, induced local arthritis, or hot water application. Selective spinal cuts included either a dorsal column (DC), a dorsal quadrant which included a DC and a dorsolateral funiculus, an anterolateral column (ALC), or a hemisection. In rats without prior exposure to injury the various types of spinal cuts were not associated with any autotomy. In rats with prior exposure to formaldehyde injection, autotomy was associated only with spinal cuts that involved the ALC. In an otherwise similar group of rats but with prior induction of local arthritis, a stronger association of ALC lesion and autotomy was observed. In an earlier study, rats with ALC lesion prior to denervation showed reduced autotomy. In this study, we demonstrated that in rats with previous exposure to heat injury, an ALC lesion was strongly associated with autotomy. Autotomy was absent, however, in rats with heat injury only. These findings strongly suggest that pain resulting from previous exposure to injury produces a memory trace in the central nervous system which can account for the phantom pains encountered in various clinical conditions. PMID- 8432367 TI - Abnormal excitability of hippocampal CA3 pyramidal neurons of spontaneously epileptic rats (SER), a double mutant. AB - The spontaneously epileptic rat (SER:zi/zi, tm/tm), a double mutant, shows both tonic convulsions and absence-like seizures characterized by low-voltage fast waves and by 5-7 Hz spike and wave-like complexes in the cerebral cortical and hippocampal EEG, respectively. Characteristics of hippocampal CA3 pyramidal neurons were examined to determine whether these neurons are abnormally excitable. When a single stimulus was given to the mossy fiber, there was repetitive firing and a depolarization shift in neurons of mature SER (over 12 weeks old), in which epileptic seizures had fully developed. However, in young SER (7-8 weeks old) and littermates (zi/zi, tm/+), which did not show any seizures, only a single spike was elicited with each single stimulation of the mossy fiber. Intracellular recording showed that the resting membrane potential was not significantly different among young and mature SER and littermates, but a long-lasting (100-200 ms) depolarizing shift accompanied by repetitive firing was observed following a single stimulation of the mossy fiber in half of the CA3 neurons of mature SER. Furthermore, the input impedance of the CA3 neurons in mature SER was lower than that in young SER and in littermates. These results indicate that SER hippocampal CA3 neurons become abnormally excitable in conjunction with the development of epileptic seizures. PMID- 8432368 TI - Expression of GAD (M(r) 67,000) and its messenger RNA in basal ganglia and cerebral cortex after ischemic cortical lesions in rats. AB - Glutamic acid decarboxylase (GAD) is present in most efferent neurons of the striatum and in interneurons both in the striatum and the cerebral cortex. We have examined the effects of unilateral lesions of the frontoparietal cortex by thermocoagulation of pial vessels in adult rats on GAD expression in the basal ganglia and in the contralateral cerebral cortex. Levels of GAD were measured in the striatum and its target areas (pallidum and substantia nigra) with radioimmunohistochemistry and an antibody specific for GAD (M(r) 67,000: GAD67); levels of the corresponding mRNA were measured at the single-cell level by in situ hybridization histochemistry with a [35S]RNA probe. Five days after surgery, GAD67 immunoreactivity was markedly increased in striatal target areas on the side of the lesion. In the striatum, increases in immunoreactivity were small at 5 days, larger at 3 weeks, and accompanied by an increase in mRNA levels lasting up to 3 months after surgery. In contrast, in the frontal cortex contralateral to the lesion, levels of labeling for GAD67 mRNA per neuron were decreased 3 weeks and 3 months after surgery. The results suggest that local ischemic lesions of cerebral cortex in adult rats lead to prolonged and opposite alterations in GAD67 synthesis in basal ganglia and contralateral cortex. PMID- 8432370 TI - 25th Annual Meeting of the Swiss Societies for Experimental Biology. Lausanne, March 25-26, 1993. Abstracts. PMID- 8432369 TI - Effects of nimodipine on two neurologic measures sensitive to sensorimotor cortex damage. AB - Seventeen rats with lesions involving the sensorimotor forepaw and hindpaw regions were tested for the ability to run along a narrow bridge without slipping and to hold on to a small-diameter dowel suspended above the ground. Nine of the animals received the calcium channel blocker, nimodipine, once per day for the first 2 weeks after surgery, while the remaining eight rats received vehicle alone. Repeated measurements over the first 3 postoperative weeks showed deficits among the rats with lesions on both tasks. The animals treated with nimodipine, however, showed much better recovery, especially after the initial testing sessions. PMID- 8432371 TI - The effects of school-based health clinics in St. Paul on school-wide birthrates. AB - School-based clinics in St. Paul have provided comprehensive health services, including reproductive health care, for almost two decades. This study examines the effects of those clinics on the birthrates in their respective schools, using a newly developed methodology with numerous advantages over previous methods for estimating student birthrates. Confidentially matching the names of female students from school records with the names of mothers on birth records at the Department of Health provided birthrates for each of the St. Paul public high schools with clinics for each year between 1971 and 1986. The results show that birthrates fluctuated dramatically from one year to the next, but school-wide birthrates were not significantly lower in the years immediately following the opening of a clinic than in the years preceding it. PMID- 8432372 TI - Oral contraceptives and reproductive cancers: weighing the risks and benefits. AB - The hypothetical incidence of reproductive cancers resulting from oral contraceptive use was estimated in several models comparing the cumulative lifetime incidence of cancer of the breast, cervix, ovary and endometrium expected in pill users with the incidence expected in nonusers. The potential number of cancer-free days that would be gained or lost by pill users was compared with similar estimates among nonusers. If five years or more of pill use were associated with a 20% increase in the risk of breast cancer being diagnosed before age 50, a 20% increase in cervical cancer risk and a 50% reduction in the risks of ovarian and endometrial cancers, then every 100,000 pill users would experience 44 fewer reproductive cancers during their lifetime than would nonusers, and would gain one more day free of cancer. If higher estimates of the five-year pill-associated risks of breast and cervical cancer are used--a 50% increased risk of each, for example--then pill users would experience more reproductive cancers than nonusers and would have 11 fewer cancer-free days of life. PMID- 8432373 TI - Adolescent males' orientation toward paternity and contraception. AB - Data from a nationally representative sample of 1,880 young men aged 15-19 reveal that neighborhood quality, parental education, race or ethnicity, and attitudes about male gender roles are related to young men's attitudes toward an unplanned pregnancy and to their contraceptive experiences. Young men who live in poor neighborhoods are more likely to be pleased about an unplanned pregnancy than those who have better living conditions (12% vs. 2%) and are also more likely to view impregnating a woman as enhancing their masculinity (8% vs. 3%). Among men with average living conditions, 12% of black adolescents view fathering a child as enhancing their masculinity, compared with 6% of white adolescents; among those with very good living conditions, these proportions were 10% and 2%, respectively. Young men whose parents had less education and those who held traditional male gender role attitudes were also more likely than their counterparts to view fathering a child as enhancing their masculinity. Regarding contraceptive behavior, sexually active black men and Hispanic men were more likely than white men to have discussed contraception with their last partner; black men were more likely to have used an effective contraceptive method the last time they had intercourse; and black men were more likely to have used a condom at last intercourse. However, young men who were aware that they had been responsible for a previous pregnancy were less likely than those who reported no pregnancies to have used an effective contraceptive the last time they had intercourse. These same young men were also more likely to report that fathering a child would please them and enhance their masculinity. PMID- 8432374 TI - Obstacles to prenatal care following implementation of a community-based program to reduce financial barriers. AB - A study of women who gave birth in a rural Oregon county during 1988-1990 found that despite the establishment of a program to provide prenatal care to low income women who could not afford it, the most common reasons cited for inadequate prenatal care were financial obstacles. All 13 financial, personal and organizational barriers studied were reported more frequently by the 236 women who received inadequate or no care than by the 246 women who received adequate care. Among the reasons most frequently cited by women who received inadequate care were difficulty paying for prenatal care (70%), difficulty with medical insurance (55%), ambivalence or fear about the pregnancy (46%) and transportation problems (42%). In a logistic regression analysis that controlled for social and demographic characteristics, six barriers were significant predictors of inadequate care: The odds of receiving inadequate care were 7.9 among women who had a poor understanding of or attached a low value to prenatal care compared with those who did not cite this barrier, 3.4 among those who cited financial difficulties, 3.4 among those who said they had difficulty scheduling appointments, 3.0 among those who suffered excessive physical or psychological stress, 2.7 among those who said they did not know where to go for prenatal care, and 1.8 among those who felt ambivalence or fear regarding the pregnancy. PMID- 8432375 TI - Injectable hormones and regulatory controversy: an end to the long-running story? PMID- 8432376 TI - The influence of community characteristics on the practice of effective contraception. AB - An analysis combining individual-level data from the National Survey of Family Growth with aggregate-level information provides evidence that the characteristics of communities influence the contraceptive decisions of currently married white women in the United States. The analysis examined the relationship between the average effectiveness level of the contraceptive methods that a woman used over a three-and-a-half-year period and community characteristics such as employment opportunities, the availability of contraceptive and abortion information and services, and the level of religious adherence in communities. Community characteristics associated with higher levels of contraceptive effectiveness were rapid population growth, high rates of unemployment, elevated levels of religious affiliation, high socioeconomic status, and ready access to family planning information and services. Community liberality was negatively associated with effective contraceptive use. The results support arguments that various community characteristics affect a woman's contraceptive choices by increasing or decreasing the costs of an unintended pregnancy. PMID- 8432377 TI - Gluconeogenesis in hepatocytes determined with [2-13C]acetate and quantitative 13C NMR spectroscopy. AB - 1. In the present study the major metabolic pathways of glucose metabolism were determined in isolated liver cells using [2-13C]acetate and 13C magnetic resonance spectroscopy. 2. The relative reaction rates of glucose synthesis to the TCA cycle were determined from the 13C distribution in glucose where the overall 13C enrichment of glucose was 6.41 +/- 1.94% (mean +/- SD; n = 6) and the mean 13C enrichment of C1, C2, C5, C6 to C3, C4 was 2.63 +/- 0.30. 3. Since the distribution of tracer in glucose is a function of the relative entry rates of pyruvate to acetyl-CoA into the oxaloacetate pool this was calculated to be 0.32 +/- 0.15 and the factor for carbon exchange (1/P) between the gluconeogenic pathway and the TCA cycle was calculated to be 1.03 +/- 0.20. 4. With this carbon exchange factor and the approximated 13C enrichment of acetyl-CoA the intramitochondrial 13C enrichment of phosphoenolpyruvate was calculated and the "true" rate of hepatic gluconeogenesis from phosphoenolpyruvate estimated. 5. Since acetate was metabolized solely in liver cells the 13C enrichment of acetyl CoA could be approximated from that of 3-hydroxybutyrate. 6. The carbon 13 enrichment of 3-hydroxybutyrate and phosphoenolpyruvate was 5.89 +/- 0.90% and 5.96 +/- 1.67%, respectively. 7. The per cent gluconeogenesis from phosphoenolpyruvate calculated as the ratio of the 13C enrichment of glucose to that of 3-hydroxybutyrate times 1/P was 107 +/- 8%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8432378 TI - Decomposition of hydrogen peroxide by metmyoglobin: a cyclic formation of the ferryl intermediate. AB - 1. Metmyoglobin reacted with H2O2 to form ferryl-myoglobin, which reverted back spontaneously to the met-form. 2. Through this cyclic reaction of myoglobin between metMb(III) and ferryl-Mb(IV), we proposed that H2O2, one of the potent oxidants in vivo, can be decomposed continuously in cardiac and skeletal muscle tissues in the absence of catalase and peroxidase. PMID- 8432380 TI - An increase in phosphatidic acid in the absence of changes in diacylglycerol in human platelets stimulated with ADP. AB - 1. ADP caused an increase in radioactivity of phosphatidic acid but not diacylglycerol in human platelets labelled with [3H]arachidonic acid. 2. The radioactivity of phosphatidic acid was significantly increased 10 sec after adding 10 microM ADP and this increase did not depend on production of thromboxane A2. 3. Thrombin (1 U/ml) caused an increase in both diacylglycerol and phosphatidic acid, the latter being much greater than that caused by ADP. 4. The results confirm that ADP stimulates phosphatidic acid production and suggest that a weak stimulus of the phosphatidyl inositol cycle, such as ADP, does not cause accumulation of diacylglycerol. PMID- 8432379 TI - Evaluation on the hydrolysis of methylumbelliferyl-tetra-N-acetylchitotetraoside by various glucosidases. A comparative study. AB - 1. In human plasma, an enzyme is present which hydrolyzes 4-methylumbelliferyl tetra-N-acetylchitotetraoside. The function of this enzyme is unknown. 2. We have examined whether hyaluronidase, neutral endoglucosaminidase, N-acetyl-beta-D hexosaminidase, aspartylglucosaminidase, beta-D-glucosidase, and chitobiase could hydrolyze MU-TACT. The results obtained are detailed below. 3. A purified commercial preparation of hyaluronidase does not hydrolyze MU-TACT. 4. Substrate specificity requirements, pH optimum and subcellular localization indicate that neutral endoglucosaminidase is distinguishable from MU-TACT hydrolase. Also commercial neutral endoglucosaminidase D and H have no affinity towards MU-TACT. 5. N-Acetyl-beta-D-hexosaminidase is different from MU-TACT hydrolase for the following reasons: (a) a purified enzyme preparation does not hydrolyze MU-TACT; (b) there is no correlation in the activity of the enzymes; (c) MU-TACT hydrolase is not deficient in cells of a patient with a deficiency of total N-acetyl-beta-D glucosaminidase; and (d) the 2 enzymes have very different chromatographic characteristics and Con A binding properties. 6. Enzyme characteristics, substrate structural requirements and a lack of correlation with MU-TACT hydrolase activity suggest that aspartylglucosaminidase, beta-D-glucosidase, and chitobiase are not involved in the hydrolysis of MU-TACT. 7. None of the enzymes which we have considered corresponds to MU-TACT hydrolase. The exact nature and the function of the enzyme remains an enigma. PMID- 8432381 TI - HMG-2 protein in developing rat brain cells. AB - 1. The distribution of HMG-2 protein was followed in unfractionated rat brain cells at different stages of development. Its amount gradually decreased and reached the lowest level in the terminally differentiated and non-proliferating cells. 2. In isolated oligodendrocyte nuclei the changes in the content of HMG-2 followed the same pattern of distribution which corresponded to their stage of development and proliferative activity, while in the terminally differentiated and non-proliferating cortical neurons a substantial amount of HMG-2 protein was present up to the twenty-eighth postnatal day. 3. In the presence of anti-HMG-2 antibodies the DNA synthetic activity of oligodendrocyte nuclei in vitro was significantly decreased. The treatment with antibodies affected mainly the DNA replicative activity of the nuclei, while their DNA repair activity remained unchanged. PMID- 8432382 TI - The interaction of cytosolic epoxide hydrolase with chiral epoxides. AB - 1. The kinetic parameters of the cytosolic epoxide hydrolase were examined with two sets of spectrophotometric substrates. The (2S,3S)- and (2R,3R)-enantiomers of 4-nitrophenyl trans-2,3-epoxy-3-phenylpropyl carbonate had a KM of 33 and 68 microns and a Vmax of 16 and 27 mumol/min/mg, respectively. With the (2S,3S)- and (2R,3R)-enantiomers of 4-nitrophenyl trans-2,3-epoxy-3-(4-nitrophenyl)propyl carbonate, cytosolic epoxide hydrolase had a KM of 8.0 and 15 microM and a Vmax of 7.8 and 5.0 mumol/min/mg, respectively. 2. Glycidyl 4-nitrobenzoate had the lowest I50 of the compounds tested in the glycidyl 4-nitrobenzoate series (I50 = 140 microM). The I50 of the (2R)-enantiomer was 3.7-fold higher. The inhibitor with the lowest I50 in the glycidol series, and the lowest I50 of any compound tested, was (2S,3S)-3-(4-nitrophenyl)glycidol (I50 = 13.0 microM). It also showed the greatest difference in I50 between the enantiomers (330-fold). 3. All enantiomers of glycidyl 4-nitrobenzoates and trans-3-phenylglycidols gave differential inhibition of cytosolic epoxide hydrolase. However, neither the (S,S)-/(S)- or (R,R)-/(R)-enantiomer always had the lower I50. 4. Addition of one or more methyl groups to either enantiomer of glycidyl 4-nitrobenzoate resulted in increased I50. However, addition of a methyl group to C2 of either enantiomer of 3-phenylglycidol resulted in a decreased I50. Finally, when the hydroxyl group of trans-3-(4-nitrophenyl)glycidol was esterified the I50 of the (2S,3S)- but not the (2R,3R)-enantiomer increased. PMID- 8432383 TI - Horse-liver glutathione reductase: purification and characterization. AB - 1. Purification of horse-liver glutathione reductase was obtained by affinity chromatography on N6-(6-aminohexyl)-adenosine-1'5'-bisphosphate Sepharose (N6 2'5'-ADP-Sepharose) and Reactive Red-120-Agarose, and chromatography on DEAE Sephadex and Sephacryl S-300. 2. The final preparation had 248 U/mg specific activity after 11,174-fold purification with 47% final recovery, and was homogeneous by SDS-electrophoresis. It showed charge heterogeneity in non denaturing electrophoresis and chromatofocusing, with several peaks of pI between 5.7 and 6.7. 3. The enzyme was homodimeric (107,000 native MW), with S20w = 6.31 S, and 41.22 A of hydrodynamic radius. It showed absorption peaks at 270, 370 and 462 nm, a characteristic of flavoproteins. 4. When NADPH was substituted by deamino-NADPH or NADH the enzyme showed 69 and 8.5% activity, respectively, while with glutathione-CoA mixed disulfide the enzyme had 23% of the activity shown with GSSG. Apparent Km values of 8.8, 680, 59, and 560 microM were measured for NADPH, NADH, GSSG and ferricyanide, respectively. PMID- 8432384 TI - Physicochemical property of bovine brain 73-kDa stress protein. AB - 1. An approximately 70-kDa protein was purified from bovine brain using an ATP Sepharose column. 2. The protein sample was found to contain two proteins (major 73 kDa and minor 72 kDa) on two-dimensional gel electrophoresis. 3. Antibodies raised against the 73- and 72-kDa proteins cross-reacted with stress-induced HSP73 and HSP72 from HeLa cells, respectively. 4. Heparin-binding peptides were obtained from trypsin digests of HSP73. PMID- 8432385 TI - Small membrane-associated GTP-binding proteins of catecholamine-secreting cells. AB - 1. Four GTP-binding proteins (23-27 kDa) were identified in membranes from PC12 cells by [alpha 32P]GTP binding to nitrocellulose blots of SDS-polyacrylamide gels. 2. The GTP-binding proteins remained associated with membranes during stimulation of intact cells by K(+)-depolarization or even after addition of Ca2+ to digitonin-permeabilized cells. 3. By two-dimensional gel electrophoresis, six GTP-binding proteins were resolved and based on their mobility, their phosphorylation state appeared independent of Ca2+. 4. Fractionation of PC12 membranes showed that these GTP-binding proteins were broadly distributed in post nuclear membranes with the plasma membranes containing the highest specific GTP binding activity. 5. Membrane fractions from bovine adrenal medulla contain similar GTP-binding proteins with GTP-binding intensity also being highest in the plasma membrane. 6. The GTP-binding proteins could be concentrated in the detergent-rich fraction upon Triton X-114 phase separation. PMID- 8432386 TI - Localization of HSP90 in rat brain. AB - 1. In rats, HSP90 (90-kDa heat shock protein) was abundant in the brain compared with the liver and kidney. Immunohistochemical studies showed the presence of HSP90 in almost all neurons in the brain. 2. On immunoblotting using an anti HSP90 antibody, HSP90 was present in a lower amount in the medulla oblongata and spinal cord. 3. In the pituitary gland, some of superficial cells of the anterior lobe adjacent to the middle lobe was specifically stained with anti-HSP90 antibody. PMID- 8432387 TI - Minimum tissue size required for hydra regeneration. AB - Small tissue pieces were excised from wild-type polyps of Hydra magnipapillata, allowed to regenerate, and the size-dependent characteristics of head regeneration were examined. The excised tissue piece was initially a square flat sheet. This piece gradually rounded up and, within 24 hr after excision, turned into a "spherical shell" which had a continuous ectodermal layer outside, a continuous endodermal layer inside, and an empty cavity at the center. The smallest spherical shell that could be produced had a diameter of 0.2 mm and contained 270-300 epithelial cells. A tissue piece too small to form a spherical shell always disintegrated, presumably due to lack of an osmotic barrier between the tissue and the environment. Of the spherical shells with a diameter of 0.2 mm, about half (47%) regenerated a head in about 5.5 days, while the rest remained as spherical shells or disintegrated. With an increase in diameter, the regeneration percentage increased, and regeneration time decreased. Similar size dependent characteristics were also observed in a computer simulation study of regeneration based on the reaction-diffusion mechanism (Gierer and Meinhardt, Kybernetik 12, 30-39, 1972). These observations are consistent with the view that two independent factors are involved in determining the minimum tissue size for regeneration. One is the amount of tissue required to form a spherical shell. A tissue piece too small to form a spherical shell cannot survive and, hence, cannot regenerate. The other may be the reaction-diffusion mechanism. A pattern might not be formed below a critical limit size set by this mechanism. PMID- 8432388 TI - Regulation of maternal messenger RNA translation during oogenesis and embryogenesis in Urechis caupo. AB - We have tested the hypothesis that the selective translation of mRNAs in oocytes and embryos is controlled by when during oogenesis individual maternal mRNAs are synthesized. In an earlier paper we described the isolation of cDNA probes to 21 maternal mRNAs which accumulate with different patterns during oogenesis in Urechis caupo (E. T. Rosenthal and F. H. Wilt, 1986, Dev. Biol. 117, 55-62). Many of these probes have now been used to analyze the translation of the maternal mRNAs in growing oocytes, full-grown oocytes, and embryos. The translation of all of the mRNAs studied changes dramatically when full-grown Urechis oocytes are fertilized. Our data do not support the idea that the translation of the different maternal mRNAs depends on when they were synthesized during oogenesis. This strongly suggests that, at some level, the ability of the cell's translational machinery to distinguish between different maternal mRNAs must reside directly, or indirectly, in the mRNA sequences. We have also found that in Urechis, as in Xenopus, the selective translation of maternal mRNAs is correlated with their selective adenylation. Consequently, we have sequenced the 3' ends of 16 translationally controlled maternal mRNAs in an effort to detect consensus sequences that might regulate adenylation. No such consensus sequences have been found, suggesting that the mRNA characteristics involved in the regulation of polyadenylation may reside in a wide variety of sequences or in more subtle features, such as secondary structure. PMID- 8432389 TI - Embigin, a member of the immunoglobulin superfamily expressed in embryonic cells, enhances cell-substratum adhesion. AB - Embigin is a glycoprotein belonging to the immunoglobulin superfamily, and is preferentially expressed before 10 days of gestation during mouse embryogenesis. To study its function, an embigin cDNA under the control of beta-actin promoter and Rous sarcoma virus enhancer was introduced into L cells. Transfectants expressing embigin were found to have enhanced cell-substratum adhesion activity, which was evident by microscopic observation and could be determined quantitatively by culturing cells on plastic dishes in serum-free medium containing 0.05% bovine serum albumin. After 6 hr of culture about 50% of the transfected cells adhered to the dish, whereas parental cells scarcely adhered. The enhanced cell-substratum adhesion was Ca2+ dependent and inhibited by an arginine-glycine-aspartic acid peptide, which competitively inhibits integrins, and also by anti-integrin antiserum. Thus, one role of embigin appears to be promotion of integrin-mediated cell-substratum adhesion. PMID- 8432390 TI - Actin is a major structural and functional element of the egg cortex of giant silkmoths during oogenesis. AB - The cortex and subcortical regions of the developing follicles and eggs of silkmoths are rich in cytoskeletal elements, particularly actin. In situ analysis using [3H]-polyuridylic acid and biotinylated oligo d(T) reveals a pattern of changes in poly(A)+ RNA distribution during oogenesis. The developing pattern of distribution of actin filaments in the ooplasm closely resembles that of poly(A)+ RNA. RNA polymerase II is also associated with the cortical cytoskeleton. Destruction of the actin filaments in the developing oocytes by cytochalasin D randomizes the distribution of mRNA and causes the displacement of RNA polymerase II from the cortex. Rhodamine-conjugated phalloidin and a monoclonal antibody against cytoskeletal actin were used in combination with laser scanning confocal microscopy to examine the details of actin distribution in the oocytes. RNA polymerase II was located in developing oocytes using both anti-Drosophila RNA polymerase II antibody and fluorescein-conjugated amanitin. PMID- 8432391 TI - CD44 positive macrophages take up hyaluronan during lung development. AB - In the present study, we examined the expression and distribution of both hyaluronan and its cell-surface receptor (CD44) during lung development in the mouse. Hyaluronan was detected by a specific binding probe, termed b-PG, which is a biotinylated mixture of proteoglycan and link protein from cartilage. Using this probe in an enzyme-linked assay, the amount of hyaluronan in relation to protein content was found to decrease as lung development progressed. In addition, histochemical staining of the embryonic lungs revealed that during early stages, relatively large amounts of hyaluronan were present in the interstitium. However, as development progressed, much of this was lost, and in the adult, hyaluronan was restricted to the regions surrounding the major blood vessels, bronchi, and bronchioles. In contrast to hyaluronan, the amount of CD44 increased as a function of development, as determined by the rat monoclonal antibody, KM-201. Histochemical staining with this antibody showed that the receptor was primarily associated with macrophages and to a lesser extent with adult bronchial and bronchiolar epithelium, vascular smooth muscle, and endothelial cells. As development progressed, the macrophages expressing CD44 increased in number, and this increase was temporarily correlated with the decrease in hyaluronan content. In addition, histochemical staining revealed that some of these macrophages contained hyaluronan in their cytoplasm, suggesting that macrophages had internalized hyaluronan from the extracellular matrix. This possibility was further supported by the fact that when newborn mice were injected with the KM-201 monoclonal antibody, which blocks the interaction between hyaluronan and the receptor, the number of hyaluronan-containing macrophages in the lungs decreased while the concentration of hyaluronan increased. Taken together, these results suggest that macrophages can internalize hyaluronan during lung development and could possibly play a significant role in its removal. PMID- 8432393 TI - Developmental expression of the rabbit 55-kDa zona pellucida protein and messenger RNA in ovarian follicles. AB - The events associated with the early stages of oocyte activation and granulosa cell (GC) differentiation during ovarian follicular development have been investigated using immunological and cDNA probes. Because zona pellucida (ZP) proteins provide excellent markers for oocyte activation during early stages of ovarian development, a cDNA encoding a full-length ZP protein with calculated molecular weight of 57,185 (rc55) and a specific antibody to the corresponding native rabbit ZP protein (R55) were developed. Immunohistochemical analysis of ovaries demonstrated that R55 was localized in follicles of animals 2 weeks and older. R55 was localized in the oocytes of primordial follicles and the oocytes and GCs of primary follicles but was undetectable in the GCs of large antral follicles. GCs were isolated from 6-week-old rabbit ovaries and cultured in defined media to demonstrate expression of rabbit ZP proteins by GCs in vitro. Rabbit ZP proteins were localized in the cytoplasm of cultured GCs if these cells were treated with monensin, a compound that blocks glycoprotein secretion. Northern blot analysis with the cDNA probe rc55 revealed that cultured GCs contained a mRNA for R55 and that there is stage-specific expression of the R55 mRNA in developing rabbit ovaries. Immunoblot analysis demonstrated that R55 is detectable at 4 weeks and accumulates in 6-, 8-, and 12-week ovaries which contain developing primary and secondary follicles. Collectively, these data illustrate developmental expression of R55 in oocytes and GCs of rabbit ovarian follicles. PMID- 8432392 TI - XLPOU-60, a Xenopus POU-domain mRNA, is oocyte-specific from very early stages of oogenesis, and localised to presumptive mesoderm and ectoderm in the blastula. AB - POU-domain proteins are a large family of transcriptional regulatory proteins, related to the homeodomain proteins, many of which are implicated in the control of gene expression during early development. We describe here the isolation of a cDNA encoding a Xenopus POU-domain protein, XLPOU-60. The predicted protein sequence of this cDNA is most closely related to the mouse germ line-specific transcription factor Oct-3/4. The XLPOU-60 gene is specifically expressed in oocytes of newly metamorphosed frogs, from the earliest stages at which transcription is known to occur. The mRNA is concentrated in the animal half of fully grown oocytes and is inherited maternally by the embryo, where it remains localised to animal cap and marginal zone cells of the blastula. Transcripts decline abruptly to a low level during gastrulation, but remain detectable throughout larval stages. However, unlike Oct-3/4, the transcript is not detectable in primordial germ cells, and XLPOU-60 is therefore probably not the functional homologue of the murine gene. We suggest that XLPOU-60 is one of the earliest genes to be transcribed in oocyte development, and that the XLPOU-60 protein may therefore be involved in initiating oocyte-specific patterns of transcription. Localisation of the transcript in the embryo may indicate that XLPOU-60 is also required for the initiation of mesoderm- and ectoderm-specific patterns of transcription in the embryo. PMID- 8432394 TI - Temporal embryonic expression of the sea urchin early H1 gene is controlled by sequences immediately upstream and downstream of the TATA element. AB - The sea urchin early histone H1 gene is expressed only during a very short interval in the life cycle of the organism. In addition to a pool of stored maternal transcripts, the gene is active from the 16-cell stage to the early blastula stage of development, at which time the gene is transcriptionally repressed. We have defined the minimal sequences required for the proper temporal expression of this gene during early embryogenesis. These sequences from -65 to +39 include the TATA element, a conserved sequence CCCACGTACGCAA (part of USE 0) just upstream of the TATA element, an Inr element at the transcription start site, and an internal sequence in the leader region of the H1 transcript. Surprisingly, we could find no role for two highly conserved elements, a GC box (USE I) and an H1-specific element (USE II), that are important in the expression of vertebrate H1 genes. The internal element functions as a positive regulator when three copies are ectopically placed upstream of an early histone H3 TATA box. A temporal regulator is localized within the USE 0 sequence CCCACGTACGCAA, and it apparently plays a role in activation and probably repression of the gene. PMID- 8432395 TI - Cell migration in cultured cerebral cortical slices. AB - In order to investigate the cellular mechanisms of migration and lamination in the mammalian cerebral cortex, we have cultured living slices of the developing telencephalon and tracked the migration of newly generated cortical neurons. Slice cultures made from neonatal ferret cortex were maintained in roller tubes and survived well for several weeks in vitro. Cells generated on Postnatal Day (P) 0 or 1 were labeled with the thymidine analog 5-bromo-2-deoxy-uridine (BrdU), and their movements were tracked during the subsequent culture period. At the beginning of the culture period, labeled cells were found almost exclusively in the proliferative zones of the cerebral wall, the ventricular and subventricular zones. Over the first week in culture, there was a dramatic movement of labeled cells out of the proliferative zones and into the cortical plate, the final destination of neocortical neurons. Comparison of the patterns of cell movement in cultured slices with that in intact littermate controls revealed that the initial migration of labeled cells into the cortical plate is similar in cultured slices and normal animals. The primary difference between migration in slice cultures and in vivo is that after longer times in culture, cells that migrate into the cortical plate fail to form the tightly clustered laminae characteristic of cells in the intact brain. Labeled cells are instead distributed more widely throughout the cortical plate and other regions of the cerebral wall. Thus, at least during the initial period of migration, cultured slices provide an experimentally manipulable system in which cell migration can be directly observed in a histotypically normal environment. PMID- 8432396 TI - A novel murine zinc finger gene mapped within the tw18 deletion region expresses in germ cells and embryonic nervous system. AB - A novel zinc finger gene, designated NT fin12, belonging to the C2H2-Kruppel-type gene family was isolated from a newborn mouse testis cDNA library by using zinc finger consensus motif probes. Northern blot analyses showed that NT fin12 mRNA was expressed during the meiotic prophase of spermatogenesis and in embryogenesis. Transcripts were localized by in situ hybridization in spermatogonia and in early spermatocytes, and in testis cords in the genital ridge as well as in oocytes and follicle cells in the ovary. In midgestational embryos at 8.5-13.5 days postcoitum, transcripts were present in the neuroectoderm, and they were progressively restricted to peripheral ganglia derived from neural crest cells and neural placodes and to the motor nerve cells in the central nervous system. Taken together these results indicate that NT fin12 functions during germ cell development and also plays a role in the specification of a subpopulation of neuroectodermal cells. Genetic linkage analyses revealed that the NT fin12 locus mapped to the deletion region of the tw18 haplotype on mouse chromosome 17. PMID- 8432397 TI - Unique expression pattern of the FGF receptor 3 gene during mouse organogenesis. AB - The actions of fibroblast growth factors (FGFs) are mediated via a family of four closely related FGF receptor genes (FGFRs 1-4). FGFR1, FGFR2, and FGFR4 have unique patterns of expression during embryogenesis suggesting that these receptors mediate different functions of FGFs during development. In the present study, we used in situ hybridization analysis to show that FGFR3 also has a unique pattern of expression during organogenesis. Like FGFR1 and FGFR2, FGFR3 was expressed in the germinal epithelium of the neural tube (9.5-16.5 days pc). However, at 1 day postpartum and in the adult brain, FGFR3 was expressed diffusely and localized in cells with morphologic characteristics of glia, a pattern distinctly different from the discrete neuronal expression of FGFR1. FGFR3 was also expressed at high levels in differentiating hair cells of the cochlear duct, but was not detected in other sensory epithelia. Outside the nervous system, the highest level of FGFR3 expression was found in the cartilage rudiments of developing bone. During endochondral ossification, FGFR3 was expressed exclusively in resting cartilage, a pattern distinct from FGFR1 and FGFR2 which are also expressed during this process. Unlike FGFR1 and FGFR2, FGFR3 was not detected in most other epithelial or mesenchymal tissues during these stages of organogenesis. The unique expression pattern of FGFR3 compared with the other FGF receptors strongly suggests that FGFR3 performs specific functions during organogenesis. PMID- 8432398 TI - Urokinase production by embryonic endocardial-derived cells: regulation by substrate composition. AB - Early events in cardiovascular morphogenesis are characterized by cell migrations and extensive tissue remodeling. We are interested in the role played by the extracellular serine protease urokinase in these events. Elevated urokinase activity and mRNA levels have been shown to be associated with the onset of ventricular trabeculation and mesenchymal cell migration in the endocardial cushion tissues of the atrioventricular canal and the outflow tract of the quail embryo. In this study, urokinase production by isolated endocardial-derived cells was found to be affected by the composition of the matrix to which the cells were exposed. Interaction of cells with a 45-kDa gelatin-binding fragment of fibronectin upregulated the production of urokinase by nearly threefold. This increase in urokinase activity had profound influences on cell motility and spreading. PMID- 8432399 TI - Expression of chimeric human transferrin-chloramphenicol acetyltransferase genes in liver and brain of transgenic mice during development. AB - Transferrin (TF) gene expression is tissue specific and is regulated during development. Transgenic mice have been developed which carry 1.2 or 0.67 kb of the TF 5' flanking region of the human TF gene fused to the bacterial chloramphenicol acetyltransferase (CAT) gene. The onset of expression of the chimeric human TF-CAT transgenes in liver and brain during development has been studied in these transgenic mice. In brain, the TF(0.67)CAT transgene began to express between 5 and 10 days after birth; in liver, the TF(0.67)CAT transgene was turned on between 10 and 20 days after birth. Endogenous mouse TF mRNA levels in liver and brain have also been measured during development by Northern analysis. In brain, the developmental expression pattern of the TF(0.67)CAT transgene is the same as the mouse endogenous TF gene; in liver, the transgene is turned on later than the endogenous mouse TF gene. DNA-protein mobility shift assays and DNase I footprinting analyses were conducted in the region of -621 to 409 bp of the human TF gene by using TF-CAT expressing liver nuclear extract from 27-day-old mice and nonexpressing liver nuclear extract from 7-day-old mice. The level of protein-DNA complex formation is several times higher in the expressing extracts, and the region from -481 to -463 bp of human TF gene is protected by the expressing extract but not the nonexpressing extracts. As demonstrated by this and other studies, the transgenic mouse model furnishes a unique opportunity to analyze developmental regulation of human transgenes. PMID- 8432400 TI - Expression of platelet-derived growth factor (PDGF) and PDGF alpha- and beta receptors in the peripheral nervous system: an analysis of sciatic nerve and dorsal root ganglia. AB - Previous studies have shown that cultured Schwann cells secrete platelet-derived growth factor (PDGF) and express PDGF receptors which transmit a mitogenic response particularly when their levels are upregulated by elevation of intracellular cAMP. In this study the expression of PDGF and PDGF alpha- and beta receptors in the peripheral nervous system (PNS) has been examined by studying dorsal root ganglia and sciatic nerve. Using the monoclonal anti-PDGF antibody, PGF-007, relatively high levels of PDGF were detected in cells of the neonatal rat dorsal root ganglia and sciatic nerve. The location and morphology of these cells indicated that they were Schwann cells while neurons of the dorsal root ganglia were less strongly labeled. The levels in Schwann cells declined during the first postnatal weeks. In the adult rat, low levels of PDGF were detected on myelinated nerve fibers while unmyelinated fibers continued to express higher levels of PDGF. Antisera specific for the PDGF alpha- and beta-receptor revealed high levels of both receptors in the neonatal rat PNS. In the adult rat peripheral nerve both receptors were detectable in unmyelinated nerve fibers. The PDGF beta-receptor, but not the alpha-receptor, was detected at low levels on myelinated nerve fibers. Teased nerve preparations, as well as freshly dissociated sciatic nerve cells, were used to substantiate the findings in frozen tissue sections. Neurons of the dorsal root ganglion expressed PDGF and PDGF alpha- and beta-receptors in all the stages of postnatal development examined. These results indicate that PDGF might play a role in the development of the PNS and in maintenance of peripheral neurons. PMID- 8432401 TI - Mechanochemical interactions between striated muscle cells of jellyfish and grafted extracellular matrix can induce and inhibit DNA replication and transdifferentiation in vitro. AB - Striated muscle tissue of jellyfish was isolated with its adhering extracellular matrix (ECM) and cultured. Without further treatment the cultured muscle cells maintain their differentiated state. If, however, the isolated tissues are combined with cell-free ECM from the jellyfish or its polyp, DNA replication and proteolytic activity are induced followed by transdifferentiation into RF-amide positive nerve cells. Changes in the mechanochemical interactions between the cells and the grafted ECM seem to induce the signals which lead to transdifferentiation. If the isolates are combined with small floating pieces of ECM most cells will leave their own ECM and overgrow the ECM graft. All cells in the combinations will then transdifferentiate. If the isolates are grafted onto large pieces of ECM kept permanently stretched on glass, a majority of cells will migrate onto the grafted ECM where they form a flat monolayer. In this case, however, DNA replication and transdifferentiation occurs mainly in those cells which have remained on or near their own ECM. Labeling experiments with [3H] thymidine demonstrate that initiation of DNA replication occurs first in those cells which bridge from the native ECM to the grafted ECM. On the other hand inhibition of DNA replication and transdifferentiation is generally suppressed whenever tissues are allowed to form a monolayer of well-stretched cells. From these observations we conclude that mechanochemical interactions between the muscle cells and their substrate are responsible for both activation and inhibition of DNA replication and transdifferentiation. PMID- 8432402 TI - Leukemia inhibitory factor and ciliary neurotrophic factor regulate expression of muscarinic receptors in cultured sympathetic neurons. AB - Regulation of muscarinic receptor expression was studied in cultured sympathetic neurons of the neonatal rat superior cervical ganglion (SCG). Leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF), both previously shown to regulate neurotransmitter development in cultured SCG neurons (Yamamori et al., 1989; Saadat et al., 1989), were examined for effects on receptor expression. Exposure of SCG neurons to LIF or CNTF (5 ng/ml) prevented the normal developmental increase in muscarinic receptors as measured by whole cell binding of N-methyl[3H]scopolamine. Reduction in receptor binding was detected within 2 to 4 days of treatment, with a 65-80% reduction after 16 days. Scatchard analysis demonstrated a reduction in total receptor number (Bmax) with no significant change in receptor affinity (Kd). Concentrations of 1 ng/ml of either factor reduced receptor expression with near-maximal effectiveness at doses of 10 ng/ml. The decrease in muscarinic receptors was not blocked by atropine, indicating that it was not agonist induced. Treatment with LIF or CNTF did not affect the survival of cultured neurons. Further, effects on receptor expression were reversible after discontinuance of treatment. Finally, treatment with either factor increased overall protein synthesis, indicating the integrity of cellular metabolism of cultures and hence the specificity of the decrease in muscarinic receptor number. LIF and CNTF thus regulate receptor as well as neurotransmitter development and could therefore play a role during synaptogenesis in the developing nervous system. PMID- 8432403 TI - Temporal regulation of Drosophila imaginal disc morphogenesis: a hierarchy of primary and secondary 20-hydroxyecdysone-responsive loci. AB - The release of 20-hydroxyecdysone at the end of the third larval instar provides a temporal signal that triggers specific developmental programs in hormone target tissues in Drosophila at metamorphosis. Imaginal discs respond to the steroid hormone by initiating morphogenesis leading to the formation of the adult head structures, appendages, and thoracic epidermis. The cellular events of morphogenesis are preceded and accompanied by 20-hydroxyecdysone-dependent activation of a set of genes encoding Inducible Membrane-bound Polysomal transcripts, the IMP-genes. Analysis of expression characteristics in imaginal discs cultured in vitro reveals that the IMP-E1 gene is expressed within 15-30 min after exposure to 20-hydroxyecdysone while the expression of the IMP-L1 gene is delayed 6-8 hr. Induction studies in the presence of cycloheximide establish that IMP-E1 is a primary response locus while IMP-L1 transcription is a secondary response. These genes are regulated at the level of transcription initiation. Differences between the induction characteristics of IMP-E1 and the early 20 hydroxyecdysone-responsive gene E74 lead us to propose an addition to the Ashburner model for the 20-hydroxyecdysone regulatory hierarchy. We suggest that the sequential temporal expression of steroid hormone-responsive genes in imaginal discs is important in organizing cellular mechanisms involved in morphogenesis of the epithelium. PMID- 8432404 TI - Distribution of microtubule-associated proteins (MAPs) in adult and embryonic mouse retinal explants: presence of the embryonic map, MAP5/1B, in regenerating adult retinal axons. AB - Microtubule-associated proteins (MAPs) are developmentally regulated proteins involved in microtubule polymerization and stabilization. We have asked whether MAPs in regenerating adult mouse retinal ganglion cell axons recapitulate the pattern of MAPs seen during development. Adult and Embryonic Day 15 (E15) mouse retinal segments were explanted onto laminin-coated coverslips and allowed to extend neurites in serum-free medium. Using a variety of monoclonal antibodies (Mabs), we stained adult and E15 explant cultures for early (MAP5) and late (MAP1, MAP2, MAP2a+b, tau) MAPs. Optic neurites growing from E15 explants were strongly immunoreactive for MAP5. Labeling was absent for MAP1 and MAP2a+b. Mabs to MAP2 and tau lightly stained axons and cell bodies, probably due to MAP2c and juvenile tau which are found in developing neurons. In adult explant cultures, both perikarya and axons were immunoreactive for MAP1. MAP2 and MAP2a+b labeled perikarya and fibers within the explant, and tau stained axons on the substrate. MAP5 immunoreactivity was intense in the adult explant cultures, labeling axons extending over the substrate and perikarya and dendrites in the explant in a pattern similar to that seen in E15 explants. In summary, adult retinal explants maintain their adult complement of MAPs, in showing high levels of MAP1, tau immunoreactivity restricted to neurites on the substrate, and MAP2 segregated into neurites and perikarya within the explant. The exception is MAP5 for which the pattern of immunoreactivity is similar in adult and E15 retinal explants. PMID- 8432405 TI - Structure, expression, and hormonal control of genes from the mosquito, Aedes aegypti, which encode proteins similar to the vitelline membrane proteins of Drosophila melanogaster. AB - Genomic and cDNA clones of a gene expressed after a blood meal in the mosquito, Aedes aegypti, were identified as having significant similarity to the vitelline membrane protein genes of Drosophila melanogaster. The predicted protein had unusually high contents of alanine, histidine, and proline and contained a region of hydrophobic amino acids that was highly conserved in the predicted protein of the D. melanogaster vitelline membrane protein genes. The 15a gene was expressed from 5 to 40 hr after a blood meal. It was expressed only in the follicle cells of the ovary, particularly in the cells surrounding the oocyte. The 15a gene was expressed in ovaries of the blood-fed, decapitated female in response to an injection of 20-hydroxyecdysone, and in ovaries from non-blood-fed females incubated with the hormone, even in the presence of cycloheximide. A second gene, with weaker homology to 15a, is presumably another member of a family of related genes, as is the case with D. melanogaster vitelline membrane protein genes. This second gene contained a coding sequence similar to a decapeptide recently isolated from mosquito ovaries as an "oostatic factor" (Borovsky et al., FASEB J. 4, 3015-3020, 1990). PMID- 8432406 TI - Amplification of insulin secretion by lipid messengers. AB - D-glucose induces a rise in pancreatic islet beta-cell cytosolic [Ca2+] by processes requiring both glucose metabolism and Ca2+ entry from the extracellular space, and this Ca2+ signal is thought to be critical to the induction of insulin secretion. Insulin secretagogues also induce phospholipid hydrolysis and accumulation of phospholipid-derived mediators in islets, including the lipid messengers DAG, nonesterified arachidonic acid, and arachidonate 12-LO products. This study offers the following viewpoints on potential roles of these lipid messengers in insulin secretion as working hypotheses: 1) the Ca2+ signal provided to the beta-cell by D-glucose induces insulin secretion only in the context of amplifying background signals provided by the beta-cell content of messengers including DAG; 2) muscarinic receptor agonists amplify glucose-induced insulin secretion in part by altering the beta-cell content of DAG; 3) the Ca2+ signal provided by metabolism of D-glucose is amplified by the level of nonesterified arachidonic acid in beta-cell membranes, which acts to facilitate Ca2+ entry; 4) metabolism of glucose induces accumulation of nonesterified arachidonate in beta-cells via activation of a recently identified ASCI-PLA2 enzyme, which may be a component of the beta-cell fuel sensor apparatus; and 5) arachidonate 12-LO metabolites are potential candidates as adjunctive modulators of beta-cell K(+)-channel activity. PMID- 8432407 TI - Muscle sympathetic nerve activity is reduced in IDDM before overt autonomic neuropathy. AB - Studies of heart-rate variability have demonstrated that abnormal cardiac parasympathetic activity in individuals with IDDM precedes the development of other signs or symptoms of diabetic autonomic neuropathy. To determine whether IDDM patients have impaired sympathetic activity compared with normal control subjects before the onset of overt neuropathy, we directly recorded MSNA. We also examined the effects of changes in plasma glucose and insulin on sympathetic function in each group. MSNA was recorded by using microneurographic techniques in 10 IDDM patients without clinically evident diabetic complications and 10 control subjects. MSNA was compared during a 15-min fasting baseline period and during insulin infusion (120 mU.m-2.min-1) with 30 min of euglycemia. A cold pressor test was performed at the end of euglycemia. Power spectral analysis of 24-h RR variability was used to assess cardiac autonomic function. IDDM patients had lower MSNA than control subjects at baseline (8 +/- 1 vs. 18 +/- 3 burst/min, P < 0.02). MSNA increased in both groups with insulin infusion (P < 0.01) but remained lower in IDDM patients (20 +/- 3 vs. 28 +/- 3 burst/min, P < 0.01). In the IDDM group, we found no relationships between MSNA and plasma glucose, insulin, or HbA1c concentrations. BP levels did not differ at rest or during insulin. Heart-rate variability and the MSNA response to cold pressor testing in IDDM patients did not differ from those in healthy control subjects. IDDM patients had reduced MSNA at rest and in response to insulin. The lower MSNA is not attributable to differences in plasma glucose or insulin, but, rather, is most likely an early manifestation of diabetic autonomic neuropathy that precedes impaired cardiac parasympathetic control. PMID- 8432408 TI - Incidence of gross proteinuria in older-onset diabetes. A population-based perspective. AB - A few population-based studies describe the incidence of gross proteinuria in people with diabetes. We performed a population-based study in southern Wisconsin of diabetic individuals diagnosed at > or = 30 yr of age either taking insulin (n = 398) or not taking insulin (n = 441). The presence of gross proteinuria (> or = 0.3 g/L) was determined by means of a reagent strip. The incidence of proteinuria in the 4-yr interval was 17.3% (95% CI 13.6-21.0) in those taking insulin and 10.7% (95% CI 7.8-13.6) in those not taking insulin. The relative risk of developing proteinuria for those in the highest level of total pack-yr smoked compared with those who had never smoked was 2.0 (95% CI 1.2-3.3) for those taking insulin and 2.5 (95% CI 1.3-4.5) for those not taking insulin. After controlling for other risk variables, the incidence of gross proteinuria was also associated with higher GHb. These data suggest that smoking and glycemic control, both potentially modifiable factors, are significant risk factors for the development of gross proteinuria. PMID- 8432409 TI - CD8+ T-cells are required for adoptive transfer of the BB rat diabetic syndrome. AB - LGLs with NK activity account for the majority of BB rat PBLs expressing CD8, and it has been suggested that these LGL/NK cells are involved in the pathogenesis of the BB rat diabetic syndrome. By using a recently developed mouse MoAb, 3.2.3, specific for rat LGL, we demonstrate that BB and WF rat LGLs are phenotypically and functionally similar. To directly assess the role of LGLs in the development of diabetes in vivo, an adoptive transfer of T-cells to young LGL/NK cell depleted diabetes-prone BB rats was performed. CD4+8- and CD4-8+ T-cells (> 98.5% pure), isolated from diabetic BB rats, were activated in vitro and injected into 30-day-old diabetes-prone BB rats. Recipients were either chronically injected with 3.2.3 (n = 15) or received an isotype-matched irrelevant MoAB (n = 14). Secondary lymphoid organs of 3.2.3-treated recipients contained < 0.1% 3.2.3+ lymphocytes, and this depletion was associated with a major decrease in the NK activity of their splenocytes. Despite this, the incidence of diabetes in 3.2.3 treated animals (40%) was not significantly different from that observed in control recipients (57%). Thus, the BB rat diabetic syndrome can be adoptively transferred in the absence of LGL/NK cells, suggesting that BB rat CD8+ T-cells are involved in the diabetogenic process. To assess the pathogenic role of CD8+ T cells, we compared the incidence of diabetes in three groups of diabetes-prone BB recipients after injection of T-cells isolated from diabetic donors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8432410 TI - Prevention of autoimmune diabetes with lymphotoxin in NOD mice. AB - We have reported previously that chronic and systemic administration of a streptococcal preparation (OK-432), an inducer of TNF, or of recombinant hTNF prevented the development of IDDM in the two animal models of IDDM-NOD mice and BB rats. In this study, we examined the effect of LT, which is structurally and functionally related to TNF, on NOD mice with diabetes. The cumulative incidence of diabetes at 30 wk of age was 22 of 40 (55%) in nontreated female NOD mice and was 4 of 8 (50%; NS), 3 of 29 (10%; P < 0.001), and 0 of 8 (0%; P < 0.001) in female mice treated three times a week from 4 to 30 wk of age with 5, 50, or 500 U of recombinant hLT, respectively. Intensity of insulitis was slightly reduced in the long-term LT-treated mice. LT productivity by ConA-stimulated spleen cells was examined in vitro. Although no significant difference was found between NOD mice and the other mouse strains, female NOD mice were slightly but significantly (P < 0.01) lower producers of LT immunoreactivity than male NOD mice, the diabetes incidence of which is lower than that of females. The SMLR as a marker of normal immune response, which was reported to be impaired in autoimmune animals including NOD mice, was significantly lower in female than male NOD mice. However, the low SMLR in female NOD mice was significantly increased by the administration of LT, and the increase was mediated by the responder cells of the LT-treated mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8432411 TI - Impact of obesity on insulin action in NIDDM. AB - Although a strong clinical association exists between obesity and NIDDM, previous studies have failed to confirm a significant relationship between the degree of obesity and the insulin resistance of NIDDM. We examined the impact of obesity on insulin-mediated glucose metabolism in 25 patients with NIDDM, whose BMI ranged from 20.8 to 36.9 kg/m2, during insulin infusions of 0.4, 1.0, and 10 microU/kg min using the glucose clamp technique. Rates of glucose disposal and HGP were compared in 14 of the diabetic patients with 19 nondiabetic control subjects of similar sex, age, and weight distribution. We found an inverse correlation between BMI and the glucose infusion rate necessary to maintain euglycemia during the first two of three insulin infusions (r = -0.63, P < 0.001, r = -0.57, P < 0.01, and r = -0.36, P = 0.08). Glucose disposal was correlated with BMI during the 1.0 mU/kg min insulin infusion (r = -0.57, P < 0.05), and glucose production was correlated at the 0.4 mU/kg min infusion (r = 0.69, P < 0.01). We concluded that obesity diminishes the insulin sensitivity of both hepatic and peripheral tissues in patients with NIDDM. The exacerbation of the insulin resistance of NIDDM by obesity indicates why weight reduction is an effective treatment for the obese NIDDM patient. PMID- 8432412 TI - Diabetes and embryonic malformations. Role of substrate-induced free-oxygen radical production for dysmorphogenesis in cultured rat embryos. AB - The aim of this study was to evaluate the role of free-oxygen radicals in the embryonic maldevelopment of diabetic pregnancy. Rat embryos cultured in vitro during early organogenesis showed growth retardation and severe malformations after exposure to 50 mM glucose, 3 mM PYR, 10 mM HBT, or 3 mM KIC. Combinations of 25 mM glucose, 2.5 mM HBT, and 1 mM KIC also elicited embryonic growth retardation and malformations. The deleterious effects on embryonic development by all agents were alleviated by addition of SOD to the culture media, which yielded increased enzyme activity in the embryos and their membranes. The endogenous SOD activity also increased in embryos subjected to a high concentration of glucose or PYR in the culture medium. Addition of the mitochondrial PYR transport inhibitor CHC to the culture media blocked the dysmorphogenesis caused by glucose and PYR, but was without effect on the teratogenic actions of HBT and KIC. These findings implicate the embryonic mitochondria as a likely site for enhanced substrate-induced production of free oxygen radicals mediating the teratogenic effect of a diabetic environment. In particular, the teratogenic process in diabetic pregnancy may depend on an increased production of free-oxygen radicals in immature embryonic mitochondria in response to a metabolic overload. This notion implies that every oxidative substrate entering the mitochondrial metabolism in excess may induce embryonic malformations and emphasizes the need for an extended metabolic surveillance of pregnant diabetic women. Consequently, optimal metabolic control should aim at normalizing the maternal serum concentrations of all possible oxidative substrates. PMID- 8432413 TI - Prevention of high- and low-dose STZ-induced diabetes with D-glucose and 5-thio-D glucose. AB - To induce hyperglycemia in mice by administration of STZ, two experimental protocols that involve different pathogenic pathways are being used. First, the intraperitoneal injection of a single high dose (HD-STZ) exerts direct toxicity on beta-cells, which results in necrosis within 48-72 h and overt permanent hyperglycemia. Second, injections of multiple low doses of STZ (LD-STZ), administered intraperitoneally on 5 consecutive days, induce both beta-cytotoxic effects and STZ-specific T-cell-dependent immune reactions. In LD-STZ models, only a combination of toxic and immunological effects result in gradually increasing hyperglycemia, provided male mice of susceptible strains are being used. In this study, we found that 5-T-G, a glucose analogue that has sulfur for oxygen in the pyranose ring, prevented, in a dose-dependent way, both HD-STZ- and LD-STZ-induced hyperglycemia and that D-G, which was only tested in the LD-STZ system, was also protective, albeit somewhat less so than 5-T-G. This protective effect was achieved by intraperitoneally injecting 5-T-G and D-G, respectively, right before each STZ injection. Protection against hyperglycemia was already achieved with a total of 3 injections of 5-T-G, 1 injection each given before the first 3 of 5 LD-STZ injections. By means of OGTT, it was determined that pretreatment with 5-T-G afforded protection from substantial beta-cell damage in vivo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8432414 TI - Methionine for valine substitution in exon 17 of the insulin receptor gene in a pedigree with familial NIDDM. AB - INSR gene mutations have been described in multiple individuals with extreme insulin resistance, but the INSR gene has not been implicated in familial NIDDM. We previously have screened members of 18 familial NIDDM pedigrees for mutations in exons encoding the tyrosine kinase domain of the INSR gene (exons 13-21) by SSCP. That analysis initially detected only patterns consistent with silent polymorphisms, but on direct sequence analysis of exon 17 we detected a Met-for Val substitution at position 985 in 1/18 pedigrees. We confirmed the substitution by sequence analysis of subcloned, PCR-amplified DNA from two pedigree members and by hybridization to labeled primers for the normal and mutant sequences. We did not find the mutation in any other individuals. Pedigree members were typed for presence or absence of the Met985 substitution by hybridization of PCR amplified exon 17 DNA to allele-specific oligonucleotide probes, and typing was confirmed by segregation of INSR haplotypes and by SSCP analysis. The substitution was present in 3 NIDDM individuals in 3 generations, including a lean individual with onset at age 24. The substitution was present in only 50% of NIDDM siblings in generation 2, however. To determine the clinical effect of the Met985 substitution, we compared the 5 nondiabetic pedigree members who carried the mutation with the 9 nondiabetic pedigree members without the mutation and with 266 members of other pedigrees. Fasting and 1-h postglucose insulin levels were not different between carriers and noncarriers (fasting, 71.4 pM vs. 74.5 pM; 1-h, 381 pM vs. 354 pM), even after correction for age, sex, and BMI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8432415 TI - Do blacks with NIDDM have an insulin-resistance syndrome? AB - NIDDM has been postulated to be a component of a more generalized metabolic syndrome, Syndrome X, caused by insulin resistance. Although the components of the syndrome include glucose intolerance, hypertension, increased TG, and decreased HDL cholesterol, their relationship to insulin resistance and/or hyperinsulinemia is controversial. Recent investigations have shown racial differences in the relationship between insulin resistance and BP in nondiabetic populations. We assessed the relationship between insulin resistance and the other components of the syndrome in 37 black men and 53 black women with NIDDM. Insulin sensitivity was determined by measuring glucose disposal with the euglycemic insulin clamp technique with a 1 mU.kg-1.min-1 insulin infusion. We also determined fasting lipid profiles and BP. In this group of black men and women with NIDDM, 30% were insulin sensitive, and 70% were insulin resistant. No correlation existed between insulin sensitivity and sBP or dBP in either sex. Fasting serum TGs were inversely correlated with insulin sensitivity for both men (r = -0.401, P = 0.02) and women (r = -0.366, P = 0.008). Serum HDL cholesterol was highly correlated with insulin sensitivity for men (r = 0.421, P = 0.01) but not for women (r = 0.071, P = 0.62). Fasting serum TG levels and serum HDL cholesterol levels were highly correlated in an inverse relationship in men (r = 0.368, P = 0.03), but not women (r = -0.199, P = 0.17). In summary, BP does not correlate with insulin resistance in blacks with NIDDM. Normal insulin sensitivity occurs in 33% of black men and 25% of black women with NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8432416 TI - Syndromes of insulin resistance in the rat. Inducement by diet and amelioration with benfluorex. AB - Insulin resistance, mainly in skeletal muscle, is linked to a cluster of prevalent diseases including NIDDM, dyslipidemias, hypertension, and cardiovascular disease. To determine if an oversupply of lipid is associated with the development of skeletal muscle insulin resistance, we examined the effect of the hypolipidemic agent benfluorex in dietary models of insulin resistance. Adult, male Wistar rats were divided into six groups and maintained for 4 wk on diets high in complex carbohydrate, fructose or fat, with or without 50 mg.kg 1.day-1 of benfluorex, given orally. Insulin action was assessed using a hyperinsulinemic (approximately 100 mU/L) euglycemic clamp, with 2-deoxyglucose tracer for individual tissue evaluation, in chronically cannulated conscious animals. Compared with starch feeding, fructose and fat feeding significantly impaired insulin action at the whole-body level (-46% and -41%, respectively, both P < 0.001), as well as in individual skeletal muscles. Fructose feeding increased circulating TGs (by 80%, P < 0.01) but not skeletal muscle TGs; whereas, fat feeding increased skeletal muscle TGs (by 59%, P < 0.01) but not circulating TGs. With benfluorex, however, diet had no effect on circulating and storage TGs; and development of skeletal muscle insulin resistance in the two diet groups was prevented. Feeding fructose but not fat significantly increased mean arterial BP (by 13%, P < 0.05), an effect prevented by benfluorex. These effects support the hypothesis that the development of muscle insulin resistance in these models is linked to local or systemic oversupply of lipid. These diet models--and the parallel effect of benfluorex on insulin resistance, lipids, and hypertension--may prove useful in the search for the mechanisms that underlie the human disorders associated with insulin resistance. PMID- 8432417 TI - An insulin-like growth factor I-resistant state in cartilage of diabetic rats is ameliorated by hypophysectomy. Possible role of metabolism. AB - This study investigated the effect of IDDM on cartilage anabolic activity in rats. Rats were injected with STZ to induce IDDM, were hypophysectomized, or were injected with STZ and hypophysectomized. After 14 days, control (intact and sham Hx) and Hx rats were normoglycemic, whereas the rats with IDDM exhibited hyperglycemia and glycosuria. The HxDb rats, however, had normal blood glucose levels and no glycosuria. Both growth, serum levels of IGF-I, and basal cartilage 35SO4 incorporation measured in vitro were decreased in the Hx, IDDM, and HxDb groups. IGF-I added in vitro significantly stimulated 35SO4 incorporation by cartilage explants from control and Hx animals, whereas explants from the animals with IDDM were unresponsive. Explants from the HxDb rats, however, were stimulated by IGF-I in a dose-related manner. Because Hx corrected the glycemic status of the IDDM rats and restored cartilage responsiveness to IGF-I, a second set of experiments was undertaken to further investigate the relationship between cellular metabolism and anabolic activity in cartilage. Cartilage explants from rats fasted for 48 h showed significantly decreased basal 35SO4 incorporation, which was as low as that in explants from rats with severe IDDM. Whereas explants from the IDDM rats were completely unresponsive, those from the fasted rats (and fed rats) were significantly stimulated by the added IGF-I. However, incubation in the presence of 2-D-G, which causes intracellular glucopenia, or in the absence of glucose, completely blocked the anabolic response to IGF-I in otherwise responsive tissues. In conclusion, an important component of diabetic growth inhibition appears to be tissue resistance to the anabolic action of IGF I, a condition that is correctable by Hx and that may be a result of metabolic impairment at the tissue level. PMID- 8432418 TI - Reduced insulin secretion by repeated low doses of STZ impairs glucose effectiveness but does not induce insulin resistance in dogs. AB - To investigate the longitudinal relationship between progressive beta-cell dysfunction and other parameters of glucose tolerance, we administered repeated low doses of STZ (10 mg/kg body wt) to dogs at 14-day intervals. STZ was discontinued after 10 doses (n = 4), the onset of fasting hyperglycemia (n = 1), or death (n = 1). Before the initial drug dose and 8 days after each treatment, an insulin-modified frequently sampled intravenous glucose tolerance test was performed to determine the integrated insulin response to glucose (0-19 min), insulin sensitivity, glucose effectiveness, and glucose tolerance. The integrated insulin response to glucose reached a nadir equal to 8% of pretreatment values by completion of the study. Despite this significant reduction in the insulin secretory response to glucose (P = 0.02), fasting plasma insulin, fasting plasma glucose, and insulin sensitivity remained constant throughout the study (P = 0.15, P = 0.71, and P = 0.5, respectively). SG, however, declined significantly below the pre-STZ treatment level in animals that received more than seven STZ doses (> 70 mg/kg STZ cumulatively, P < 0.03). In summary, when fasting normoglycemia is maintained, a 92% reduction in insulin secretory capacity and repeated low doses of STZ may alter glucose effectiveness but does not directly affect insulin sensitivity. PMID- 8432419 TI - Differential expression of glutamic acid decarboxylase in rat and human islets. AB - The GABA synthesizing enzyme GAD is a prominent islet cell autoantigen in type I diabetes. The two forms of GAD (GAD64 and GAD67) are encoded by different genes in both rats and humans. By in situ hybridization analysis of rat and human pancreases, expression of both genes was detected in rat islets, whereas only GAD64 mRNA was detected in human islets. Immunocytochemical analysis of rat and human pancreatic sections or isolated islets with antibodies to GAD64 and GAD67 in combination with antibodies to insulin, glucagon, or SRIF confirmed that a GAD64 and GAD67 expression were beta-cell specific in rat islets. In contrast, only GAD64 was detected in human islets and was, in addition to beta-cells, also surprisingly localized to some alpha-cells, delta-cells, and PP-cells. In long term (4 wk) monolayer cultures of newborn rat islet cells, GAD64 expression remained beta-cell specific as observed in vivo, whereas GAD67 was localized not only to the beta-cells but also in the alpha-cells and delta-cells. A small but distinct fraction of GAD positive cells in these monolayer cultures did not accumulate GABA immunoreactivity, which may indicate cellular heterogeneity with respect to GABA catabolism or GAD enzyme activity. In a rat insulinoma cell line (NHI-6F) producing both glucagon and insulin depending on the culture conditions, GAD64 expression was detected only in cultures in which the insulin producing phenotype dominated. In conclusion, these data demonstrate that the two GAD isoforms are differentially expressed in rat and human islets but also that the expression differs according to culture conditions. These findings emphasize the need to consider both the species and culture conditions of islets. PMID- 8432420 TI - Islet cell DNA is a target of inflammatory attack by nitric oxide. AB - NO has been identified recently as the prime islet-toxic product of inflammatory macrophages. The adverse effects of IL-1 on isolated islets also have been reported to involve NO. We now show that exposure of an islet cell suspension to the NO donor nitroprusside or to activated macrophages leads to DNA strand breaks. Macrophages did not induce DNA damage in the presence of the NO synthase inhibitor NG-methyl-L-arginine. DNA strand breaks were demonstrated at the level of single cells by a modified nick-translation procedure and confirmed by analysis of DNA fragmentation by gel electrophoresis. DNA strand breaks occurred within 1 h and preceded islet cell lysis. DNA damage could not be prevented by inhibitors of endogenous endonucleases. We conclude that islet cell DNA is an early target of NO action. PMID- 8432421 TI - Quantitative analysis of neuronal damage induced by tri-ortho-cresyl phosphate in Wistar rats. AB - A quantitative analysis of neuronal damage was performed on the fasciculus gracilis (FG) of the cervical spinal cord in male Wistar rats that received orally a single dose of tri-ortho-cresyl phosphate (TOCP) at 1500 mg/kg. FG tissues were sampled at 1, 2, and 3 weeks after treatment and examined histopathologically. Wallerian degeneration of myelinated nerve fibers was observed in FG at 2 weeks. Morphological changes were most evident at 3 weeks after treatment and the number of fibers was reduced. Ultrastructurally, axonal swelling due to the accumulation of cytoplasmic contents was observed near the node of Ranvier in the affected animals, indicating paranodal degeneration. Axonal atrophy and swelling in organophosphorus-induced delayed neuropathy (OPIDN) were evaluated quantitatively using a computer-assisted image analyzer. Morphometric examinations on semi-thin sections and frozen sections stained with Nauta's method were demonstrated to be useful for objective evaluation of OPIDN in the rat. PMID- 8432422 TI - Assessment of the reproductive toxic potential of dermally applied 2-hydroxy-4 methoxybenzophenone to male B6C3F1 mice. AB - The potential of 2-hydroxy-4-methoxybenzophenone (HMB) to cause male reproductive toxicity was assessed in B6C3F1 mice. HMB was administered topically for 13 weeks (5 days/week) to groups of 10 mice each at dosages of 0, 10, 20, 100, or 400 mg/kg/day. Additional high dosage and control mice were also included and euthanized at interim time points to characterize the time course of any effects. After 91 days (or at interim periods) mice were euthanized and reproductive organ weights, cauda epididymal sperm concentration and proportion of motile and abnormal sperm, and testicular spermatid concentration were determined. Testicular histology was evaluated in fixed tissue. HMB treatment had no effect on body weight gain or any of the male reproductive parameters assessed at any time point. These results indicate that topically applied HMB has no reproductive toxic potential in male B6C3F1 mice at dosages as high as 400 mg/kg/day. PMID- 8432423 TI - Comparative ability of various PCBs, PCDFs, and TCDD to induce cytochrome P450 1A1 and 1A2 activity following 4 weeks of treatment. AB - Toxic equivalency factors (TEFs) have been proposed for dibenzo-p-dioxins, dibenzofurans, and polyhalogenated biphenyls. The proposed toxic equivalency factors (TEFs), which are presently being evaluated in our laboratory, are currently used to estimate the potential health risk associated with exposure to complex mixtures containing these chemicals. In preliminary studies, equally potent doses, based on the published TEFs and relative enzyme-inducing potency, of 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD), 2,3,7,8-tetrachlorodibenzofuran, 1,2,3,7,8-pentachlorodibenzofuran, 1,2,3,4,6,7,8,9-octachloro-dibenzofuran, 3,4,3',4'-tetrachlorobiphenyl, 2,3,4,3',4'-pentachlorobiphenyl, 3,4,5,3',4' pentachlorobiphenyl, 2,3,4,3',4',5'-hexachlorobiphenyl, 2,3,4,5,3',4' hexachlorobiphenyl, and 3,4,5,3',4',5'-hexachlorobiphenyl were administered to female B6C3F1 mice 5 days a week over a 4-week period. Hepatic, skin, and lung cytochrome P450 1A1 and hepatic 1A2 activities were determined for all chemicals tested and compared to those from TCDD-treated mice. These initial studies indicate that the present TEFs do not reliably predict induction potency for many of the chemicals. Furthermore, our data suggest that the relative inductive potency of these chemicals may be tissue specific and that estimates of TEFs based on hepatic ethoxyresorufin O-de-ethylase activity may not accurately reflect the potency of these chemicals in nonhepatic tissue. The TEFs proposed for the "dioxin-like" polychlorinated biphenyls (PCBs) overestimate the potency of these compounds by factors of 10-1000. The present study indicates that more experimental data are required before TEFs for PCBs should be used in regulatory decision making. PMID- 8432424 TI - The effects of feed restriction on reproductive function in Swiss CD-1 mice. AB - Many test compounds used in toxicity studies produce a "systemic" toxicity manifested as reduced body weight gain. While it is known that reduced weight gain during juvenile growth reduces or delays reproductive competence, the effects of adult-onset feed restriction (FR) and inhibited weight gain on the reproductive system of mice are poorly known. To gain some information on the effects of graded body weight reduction, or reduced body weight gain, on commonly used reproductive endpoints, the studies reported below were conducted at two laboratories, using adult mice that were maintained at 90, 80, and 70% of concurrent control body weight (CBW) for up to 21 weeks. Estrous cyclicity and fertility in the females were significantly affected. While male fertility was variably affected, there was a significant decrease in the number of epididymal sperm and in the number of testicular spermatids in the 70% CBW groups. Testis weight was conserved in both studies; relative testis weight increased in all FR groups. These data can improve the interpretation of future studies by helping to separate chemically induced changes from those produced by reduced body weight gain. PMID- 8432425 TI - The effects of feed restriction on reproductive function in Sprague-Dawley rats. AB - Although it is known that severe feed restriction (FR) and weight reduction (to 50-60% of control values) will sharply impair rat reproduction, few data exist on the effects of less severe body weight reduction. In the present studies, adult Sprague-Dawley rats were feed restricted and maintained at 90, 80, and 70% of control body weight (CBW) for up to 17 weeks. In females, this treatment had no effect on fertility or total number of implants per dam, but transiently increased the length of the estrous cycle and decreased by 20% the number of corpora lutea in the 70% CBW females. Ovary weight at necropsy was decreased only in the 70% CBW group. Liver and kidney weights varied with body weight. In males, fertility was not affected when they were mated to nonrestricted females. While prostate and seminal vesicles weight varied with body weight, testis and epididymis weights were unchanged by any degree of FR, as were the number of sperm in the cauda epididymis and the number of homogenization-resistant spermatids in the testis. The percentage motile sperm was slightly decreased at all levels of FR. These data show that the Sprague-Dawley rat is largely resistant to adverse reproductive changes caused by feed restriction to 70% CBW. These data should be of use in interpreting changes seen in toxicity studies that produce weight-reduce Sprague-Dawley rats. PMID- 8432426 TI - Immunotoxic effects of the color additive caramel color III: immune function studies in rats. AB - Administration of the color additive caramel color III (AC) may cause a reduction in total white blood cell counts in rats due to reduced lymphocyte counts. Beside lymphopenia, several other effects in rat have been described. The effects are caused by the imidazole derivative 2-acetyl-4(5)-(1,2,3,4 tetrahydroxybutyl)imidazole (THI) and occur in rats fed a diet low in vitamin B6. In the present paper, immune function studies on AC and THI with rats fed a diet low, but not deficient in vitamin B6 are presented and discussed. Rats were exposed to 0.4 or 4% AC or to 5.72 ppm THI in drinking water during and for 28 days prior to the start of immune function assays. Resistance to Trichinella spiralis was examined in an oral infection model and clearance of Listeria monocytogenes upon an intravenous infection was studied. In addition, natural cell-mediated cytotoxicity of splenic and nonadherent peritoneal cells and the antibody response to sheep red blood cells were studied. From the results it is concluded that exposure of rats to AC or THI influenced various immune function parameters. Thymus-dependent immunity was suppressed, while parameters of the nonspecific resistance were also affected, as shown by a decreased natural cell mediated cytotoxicity in the spleen and an enhanced clearance of L. monocytogenes. PMID- 8432427 TI - Persistent dysregulation of IgA production and IgA nephropathy in the B6C3F1 mouse following withdrawal of dietary vomitoxin (deoxynivalenol). AB - To assess whether vomitoxin-induced dysregulation of IgA production and IgA nephropathy are reversible, relevant immunologic parameters were compared among experimental groups of B6C3F1 mice that were fed: (1) 25 ppm vomitoxin in AIN-76A semipurified diet for 24 weeks (treatment group), (2) 25 ppm vomitoxin for 8 weeks and then control diet for 16 weeks (withdrawal group), and (3) control diet for 24 weeks (control group). Levels of serum IgA and microhematuria index in the treatment group were elevated after 4 to 8 weeks and continued to increase with further vomitoxin exposure. IgA immune complexes and mesangial IgA deposition, as quantitated by interactive laser cytometer image analysis, were also increased with toxin exposure at Weeks 8, 16, and 24, whereas IgM, IgG, and complement component C3 deposition were unaffected or depressed. Serum IgA, microhematuria index, and mesangial IgA deposition in withdrawal mice remained elevated over those of the controls at Weeks 16 and 24 but were less than those of the treatment group. Cell recovery from Peyer's patches (PP) as well as the percentages of IgA+ and CD4+ cells in PP and spleen at Weeks 16 and 24 were greater in treatment mice than in controls, but only the percentage of IgA+ cells in PP was elevated in the withdrawal mice at these the same time points. When IgA secretion by unstimulated and LPS-stimulated splenic lymphocytes was used as the measure of systemic production, it was elevated in both treatment and withdrawal mice at Weeks 16 and 24. The results indicated that experimental dysregulation of IgA production and IgA nephropathy persisted up to 4 months after a discrete period of dietary vomitoxin exposure, but that the severity of these effects did not increase in a progressive fashion. PMID- 8432428 TI - Percutaneous absorption of pentachlorophenol from soil. AB - Pentachlorophenol (PCP) is one of the most heavily used pesticides. About 80% of PCP is used for wood preservation, whereas the remainder is used as an herbicide, fungicide, and disinfectant. PCP is a probable human carcinogen, based on animal studies. Illness and death have been reported where PCP is in direct contact with skin. PCP is the most ubiquitous compound found when the general population is screened for pesticide residue. PCP is found in soil as well as other environmental sources. Our objective was to determine the skin bioavailability of PCP from soil and from the control vehicle acetone. In vivo in the Rhesus monkey, percutaneous absorption of PCP was 24.4 +/- 6.4% of applied dose from soil and 29.2 +/- 5.8% of applied dose from acetone vehicle for a 24-hr exposure period. This amount of absorption makes PCP one of the more extensively absorbed compounds to date. Additionally, the 14C half-life was 4.5 days following both intravenous and skin administration of [14C]PCP. These data suggest high bioavailability and an extended biological interaction period with the long half life. In vitro percutaneous absorption with human cadaver skin and human plasma receptor fluid underestimated the in vivo absorption. Receptor fluid accumulation was 0.6 +/- 0.09% and 1.5 +/- 0.2% for two skin sources for PCP in acetone vehicle and 0.01 +/- 0.00% and 0.00 +/- 0.08% for two skin sources with soil vehicle. Skin content after skin surface wash ranged from 2.6 to 3.7% for acetone vehicle and 0.07-0.11% for soil vehicle. Overall accountability for in vitro dose ranged from 81 to 96%. PMID- 8432429 TI - Hepatic CYP1A1 induction in rainbow trout by continuous flowthrough exposure to beta-naphthoflavone. AB - In order to assess the usefulness of CYP1A1 mRNA measurement as an environmental biomarker it was necessary to determine if hepatic P450 CYP1A1 mRNA induction is sustained during constant exposure to hepatic monooxygenase inducers. To accomplish this, rainbow trout (Oncorhynchus mykiss) were exposed, under flowthrough conditions, to beta-naphthoflavone (beta-NF), a known CYP1A1 inducer in fish. Trout were exposed to a beta-NF concentration of 1.0 mg beta-NF/liter, using dimethylformamide as carrier, for 1, 2, 4, and 8 days, followed by depuration in clean water for 1, 8, 14, and 35 days. In a second experiment, trout were exposed to beta-NF concentrations of 0.05, 0.10, and 0.50 mg beta NF/liter, using dimethylformamide as carrier, for 1, 3, 7, and 14 days, followed by depuration for 7 and 28 days. At the 1.0-mg beta-NF/liter concentration, ethoxyresorufin-O-deethylase (EROD) activity was significantly decreased by 4 days of exposure when compared to controls. At beta-NF concentrations of 0.05 to 0.50 mg beta-NF/liter EROD activity was increased compared to controls but was inversely related to the beta-NF concentration. Hybridizable CYP1A1 mRNA was increased approximately 40-fold over control levels at concentrations of 0.05 to 0.50 mg beta-NF/liter for 1, 3, and 7 days of exposure. In a third experiment, trout exposed to 0.05 mg beta-NF/liter for 2, 6, 12, 24, 32, 40, and 48 hr had increased (45- to 167-fold) EROD activity by 18 and 48 hr, respectively. Immunoreactive CYP1A1 protein was increased 46-fold at 48 hr and CYP1A1 mRNA was increased 29-fold at 48 hr of continuous beta-NF exposure. This is in contrast to previous experiments using intraperitoneal injection of beta-NF in which the induced CYP1A1 mRNA decreased to near control levels by 48 hr after injection. These data indicate that both CYP1A1 catalytic activity and immunoreactive protein are decreased at high inducer concentrations while mRNA levels remain elevated and continue to increase over time during continuous exposure. In a fourth experiment trout were continuously exposed to concentrations of 0.625, 1.25, 2.5, 5.0, and 10.0 micrograms beta-NF/liter, using dimethylformamide as carrier, for 1, 3, 7, 14, and 21 days, followed by clean water depuration for 1, 3, 7, 14, and 21 days EROD activity was significantly increased in a concentration-dependent manner over control by Day 1 of exposure with concentrations of 2.5, 5.0, and 10.0 micrograms beta-NF/liter.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8432430 TI - Application of microencapsulation for toxicology studies. III. Bioavailability of microencapsulated cinnamaldehyde. AB - The bioavailability of microencapsulated cinnamaldehyde (CNMA) was investigated in male F344 rats. Rats were gavaged with CNMA in corn oil using either microencapsulated or the neat chemical at doses of 50, 250, and 500 mg/kg. No differences between the two formulations at any of the doses were found in either CNMA blood concentration profiles or in the rate of urinary hippuric acid excretion. Both formulations showed a low bioavailability (< 20%) at 250 and 500 mg/kg. Regardless of the formulation used, oral gavage of CNMA significantly increased the urinary excretion of hippuric acid. About 75% of the dose of CNMA was metabolized to hippuric acid and recovered in the urine. The total amount of hippuric acid recovered in a 50-hr urinary collection correlated well with the CNMA dose. The data suggest that there was complete release of CNMA from the microcapsules and that microencapsulation of CNMA does not affect its bioavailability or its metabolism. Since CNMA microcapsules are stable in rodent diet, the microencapsulation of CNMA, and perhaps other labile chemicals, will prevent degradation and facilitate the testing of such compounds in toxicology studies. PMID- 8432431 TI - Near-lifetime exposure of the rat to a simulated urban profile of nitrogen dioxide: pulmonary function evaluation. AB - To investigate the potential for up to a near-lifetime exposure to high-ambient levels of nitrogen dioxide (NO2) to induce functional lung damage, groups of rats were exposed to air or a simulated urban profile of NO2 (0.5 ppm background, 1.5 ppm peak) for 1, 3, 13, 52, or 78 weeks. The dynamic, static, and diffusional characteristics of the lung were evaluated postexposure in anesthetized rats. Furthermore, for the 13-, 52-, and 78-week groups, additional animals were tested after a 6-, 26-, or 17-week period in filtered air, respectively. No significant NO2 differences between exposed and control animals were found for the nitrogen washout, compliance, lung volume, or diffusion capacity of carbon monoxide measurements. At 78 weeks, however, a reduction in delta FEF25%, an estimate of convexity in the later portion of the forced expiratory flow volume curve, was observed. Breathing patterns and mechanisms were also assessed postexposure in a parallel group of similarly exposed unanesthetized rats. These rats were examined during a filtered air, 4 and 8% carbon dioxide (CO2) challenge. In the unanesthetized rat, frequency of breathing was significantly decreased and tidal volume, expiratory resistance, and inspiratory and expiratory times tended to increase. For several of these variables, the largest response also occurred at 78 weeks and seemed to be exacerbated by CO2 challenge.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8432432 TI - The toxicologic and oncogenic potential of JP-4 jet fuel vapors in rats and mice: 12-month intermittent inhalation exposures. AB - Three-hundred Fischer 344 rats and 300 C57BL/6 mice of each sex were divided into three treatment groups and exposed intermittently (6 hr/day, 5 days/week) to JP-4 jet fuel vapors at concentrations of 0, 1000, and 5000 mg/m3 for 12 months. At exposure termination, 10% of the animals were killed and those remaining were held for a 12-month postexposure tumorigenesis observation period. Pathologic findings in male rats revealed treatment-related renal toxicity and neoplasia consistent with the male rat unique alpha 2 mu-globulin nephropathy syndrome. Distinct JP-4-induced respiratory toxicity was not observed, and pulmonary neoplasms were not significantly increased in any treatment group. Benign hepatocellular adenomas were slightly increased in high-dose female mice, but the trend was reversed in male mice. Other pathologic findings were regarded as equivocal or compatible with expected biologic variation. The study did not demonstrate target organ toxicity or carcinogenesis which could be extrapolated to other species. PMID- 8432433 TI - Did you say 'sarcopenia'? PMID- 8432434 TI - HMOs: medicine, American style. PMID- 8432435 TI - Community-acquired pneumonia: diagnosis and therapy of older adults. AB - Community-acquired pneumonia is a common problem in older adults and is associated with substantial morbidity and mortality. Diagnosis may be difficult, because signs of respiratory involvement may be absent and either constitutional or CNS symptoms may predominate. Elevated respiratory rate may be an important diagnostic clue. No specific pathogen is identified, and therefore empiric therapy is indicated in up to 50% of patients. The decision to hospitalize those over age 65 for parenteral antibiotic therapy is individualized. After 3 to 5 days of i.v. antibiotics oral therapy can be initiated upon favorable clinical response in the absence of proven metastatic foci of infection. Lack of response should prompt reassessment. Immunization with both the pneumococcal and viral influenza vaccines is indicated for most older patients. Discontinuation of smoking should also be encouraged. PMID- 8432436 TI - Anxiety in the older patient: differential diagnosis and treatment. AB - Anxiety in older patients is more often a symptom of an underlying mental or physical disorder than a primary diagnosis. Its various forms include situational anxiety, adjustment disorder, and phobias. A search for underlying organic causes is important, as age-related diseases, drug side effects, and substance abuse/withdrawal may have etiologic significance. Anxiety may also mask primary psychiatric disorders such as depression or delirium. Therapy requires treating any underlying psychiatric illness and seeking psychosocial intervention for functional causes. If medical therapy is indicated, short-acting benzodiazepines are the first choice, but patients should be followed closely for possible side effects. PMID- 8432437 TI - Ocular vascular disease: in-office primary care diagnosis. AB - Central retinal artery occlusion occurs most commonly between the ages of 50 and 70 years, and nearly one-half (45%) of patients also have carotid artery disease. Other causes of vision-threatening vascular disease include atherosclerosis, embolism, hypertension, diabetes mellitus, and valvular disease. Symptoms vary, depending on the ocular structures involved. The patient's symptoms are an important clue to the diagnosis of peripheral or posterior retinal vascular occlusion, macular blood vessel disease, intravitreal hemorrhage, optic nerve ischemia, and ocular ischemic syndrome. The patient's ocular symptoms should lead to investigation for clinical signs of ocular vascular disease (eg, hemorrhage, "hard" or "soft" exudates, neovascularization, retinal edema, pallor, emboli, vessel narrowing, or atriovenous crossing changes). PMID- 8432438 TI - Microvascular abnormalities in the mucosal prolapse syndrome. AB - Twenty two cases of colorectal mucosal prolapse from a variety of clinical situations were examined histologically to identify changes in the microvasculature which may predispose to ulceration. The findings were compared with 10 tubular adenomas and 10 hyperplastic polyps. Fibrin insudation into vessel walls and thickened mucosal vessels were significantly associated with the presence of ulceration. Possible mechanisms of ulceration are discussed, and an hypothesis based on a microvascular pathogenesis is presented. PMID- 8432439 TI - Role of intragastric and intraoesophageal alkalinisation in the genesis of complications in Barrett's columnar lined lower oesophagus. AB - Patients with Barrett's columnar lined lower oesophagus have severe acid gastrooesophageal reflux and may develop complications, including ulceration, stricture, and carcinoma. The aim of this study was to establish if a relationship exists between the pH profile in the oesophagus and stomach and the development of complications in patients with Barrett's columnar lined lower oesophagus. Twenty four hour ambulatory oesophageal pH monitoring was performed in 26 patients with Barrett's columnar lined lower oesophagus and combined with 24 hour ambulatory gastric pH monitoring in 16. Ten of the 26 with Barrett's columnar lined lower oesophagus had complications including stricture (eight), deep ulceration (one), and carcinoma (one). Oesophageal acid exposure (% time < pH 4) was similar in patients with or without complications (19.2% v 19.3% p > 0.05). Oesophageal alkaline exposure (% time > pH 7) was greater in patients with complications (24.2% v 8.4% p > 0.05). Of the 16 patients who underwent gastric pH monitoring there was a clear relationship between gastric and oesophageal alkalinisation in 13. These results support the hypothesis that complications in Barrett's columnar lined lower oesophagus develop in association with increased exposure of the oesophagus to an alkaline environment which appears to be secondary to duodenogastric reflux. The routine use of 24 hour ambulatory gastric pH monitoring in conjunction with oesophageal pH monitoring can help identify those patients at risk. PMID- 8432440 TI - Effect of phospholipids and their molecular species on cholesterol solubility and nucleation in human and model biles. AB - Much research in the pathophysiology of gall stones has been devoted to various molecular species of bile salts. Recent findings have shown the importance of phospholipids in biliary pathophysiology. In the present study the addition of increasing doses of egg lecithin to human and model biles progressively prolonged the nucleation time. Concurrently biliary cholesterol was shifted from the vesicular to the non-vesicular carrier(s) while the cholesterol/phospholipid ratio of the remaining vesicles was progressively lowered. Model bile solutions of identical lipid concentration were prepared using phosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine as the only phospholipid. With phosphatidylethanolamine most of the cholesterol was shifted to the vesicular carrier while phosphatidylserine shifted most of the cholesterol to the non vesicular carrier(s). With phosphatidylcholine the cholesterol was distributed in both carriers. Phosphatidyl choline species composed of various acyl fatty acids in the sn-1 and sn-2 positions were used as the sole phospholipid in otherwise identical model bile solutions. With palmitic acid in the sn-1 position and arachidonic acid in the sn-2 position most of the cholesterol was found in the non-vesicular carrier. When stearic acid was used in sn-2 position instead of arachidonic acid most of the cholesterol was found in the vesicular carrier. These and other variations in phospholipid molecular species shifted cholesterol among its carriers and also modified the nucleation time of model biles. Most of these effects were also found upon addition of the various phospholipid species to human biles. These findings show the importance of phospholipid species in biliary pathophysiology and may be useful when trying to manipulate cholesterol carriers and solubility in bile. PMID- 8432441 TI - A laparoscopic technique for full thickness intestinal biopsy and feeding jejunostomy. AB - A laparoscopic technique is described, suitable for both full thickness intestinal biopsy and placement of a feeding jejunostomy tube. Its application in three cases is reported. The method is simple, permits full laparoscopic examination of the abdominal contents and being minimally invasive, facilitates early patients recovery. PMID- 8432442 TI - Double blind trial of oral fluticasone propionate v prednisolone in the treatment of active ulcerative colitis. AB - Fluticasone propionate is a corticosteroid with the potential for topical treatment of ulcerative colitis because of low systemic bioavailability. The drug was compared with prednisolone in the management of active left sided or total ulcerative colitis. Two hundred and five patients were studied in the multicentre four week double blind study. Prednisolone was given in a dose of 40 mg daily orally, reducing over four weeks to 10 or 20 mg. Fluticasone propionate was given in an oral daily dose of 20 mg. The primary end point was the investigator's overall assessment of response. Patient's assessment, sigmoidoscopic appearance, and histology were also studied. Patients improved more rapidly with prednisolone. Differences between the two groups were significant at two weeks. At four weeks differences were not significant, but there was a trend in favour of prednisolone. Corticosteroid side effects were minimal in the fluticasone propionate group, and there was minimal suppression of the hypothalamic pituitary adrenal axis. Fluticasone propionate 20 mg daily is not as effective in the treatment of active ulcerative colitis as prednisolone tapering from 40 mg daily to 10 or 20 mg. The complete absence of suppression of the corticoadrenal axis by fluticasone propionate was encouraging, however, and a higher dosage schedule should be assessed. PMID- 8432443 TI - Contractile activity of the human colon: lessons from 24 hour studies. AB - The motor function of the colon is probably the least understood of the various hollow viscera of the human body. This is partly because of the marked variability of colonic motor function and the short recording periods usually used, generally not exceeding three hours. Most of the data available on human colonic motility originate from investigations conducted in the most distal portions of the viscus, because of technical difficulties in reaching its proximal portions. Although attempts have been made to solve these problems through the ingestion of radiotelemetric pressure sensors, these efforts have been hampered by intermittent signal loss and the inability to control the location of the capsule within the gastrointestinal tract. To overcome these problems, techniques have recently been developed that permit prolonged recordings (24 hours or more) of myoelectrical and contractile activity of the human colon, with both perfused and solid-state manometric systems. The present paper reviews the current experience in 24 hour recording from the human colon, with a primary emphasis on the more forceful propulsive contractile activity associated with the so called mass movements. PMID- 8432444 TI - Perforation from endoscopic small bowel biopsy. AB - Two patients, having undergone an apparently straightforward endoscopy with small bowel biopsy, developed a perforation. One, who proved to have normal small bowel mucosa, needed laparotomy and suturing of the duodenal perforation. The other, who had coeliac disease, settled with conservative management. PMID- 8432445 TI - Familial primary gastric lymphoma. AB - Familial lymphoma is uncommon and is usually associated with various forms of hereditary immunodeficiencies. Primary gastric lymphomas that occurred in three adults from the same family, who had no overt immunodeficiency or cancer of non lymphomatous origin, are reported. Two sisters presented with a low grade lymphoma of the mucosa associated lymphoid tissue type. Their father presented with a high grade form of later onset. All lymphomas have been phenotypically characterised as being of B cell origin. Epstein-Bar virus DNA was detected by polymerase chain reaction in the biopsy specimen of the high grade lymphoma but bcl-2/JH protooncogene rearrangement, t (14:18), was not identified in either the low or high grade lymphoma specimens tested. PMID- 8432446 TI - Location of the lower oesophageal sphincter and the squamous columnar mucosal junction in 109 healthy controls and 778 patients with different degrees of endoscopic oesophagitis. AB - In this study the location of the lower oesophageal sphincter measured by manometry and the location of the squamous columnar junction measured by endoscopy were determined in 109 healthy controls and 778 patients with different degrees of endoscopic oesophagitis. No significant differences in the prevalence and severity of the heartburn and regurgitation were observed when different degrees of oesophagitis were compared but dysphagia was more common and severe in patients with complicated Barrett's oesophagus (p < 0.001). This group also showed a male predominance and older age compared with other groups. The total length of the oesophagus, measured by the location of the distal end of the lower oesophageal sphincter was similar in all patients; however, the location of the squamous columnar junction extended more proximally and was related to the increasing severity of endoscopic oesophagitis. The manometric defects at the cardia were more frequent in severe oesophagitis (p < 0.001). These results suggest that, during the course of oesophagitis, the squamous columnar junction is displaced proximally. This displacement is limited to the mucosa, however, and does not involve the muscular layer, because the lower oesophageal sphincter undergoes no dislocation. PMID- 8432447 TI - Gastroscopic follow up of pernicious anaemia patients. AB - To assess the value of gastroscopic cancer surveillance of patients with pernicious anaemia, 56 patients were re-endoscoped and biopsied after three years. In addition, changes in the density of fundic mucosal endocrine cells were evaluated morphometrically. Two cases (3.6%) of early gastric cancer and two cases of small gastric carcinoid tumours (3.6%) were detected in addition to the five carcinoids that had been found at the initial endoscopic screening. Nodular argyrophil cell hyperplasia and morphometric density of argyrophil cells were not stable phenomena: nodular hyperplasias regressed in five patients, remained similar in six, and progressed to a small carcinoid tumour in one. Serum gastrin concentrations did not correlate well with changes in the endocrine cell density. Regular endoscopic surveillance for gastric cancer may be beneficial and realistic in young patients with pernicious anaemia while the importance of fundic endocrine cell hyperplasia and that of small gastric carcinoids need further study. PMID- 8432448 TI - Cholecystokinin octapeptide stimulates phasic and tonic pyloric motility in healthy humans. AB - Stimulation of localised pyloric contractions may be an important mechanism in the slowing of gastric emptying by cholecystokinin infusion. The effect of cholecystokinin octapeptide on fasting pyloric motility was investigated in 14 healthy volunteers. Antral, pyloric, and duodenal pressure responses to normal saline and graded injections of cholecystokinin octapeptide (5, 10, and 20 ng/kg) were measured. Injections were given double blind and in randomised order. All doses of cholecystokinin octapeptide initially stimulated (p < 0.05 cf saline) phasic pressure waves localised to the pylorus--the median number of pyloric pressure waves in the 5 minutes after injection being 0, 3.5, 6, and 7 for the saline and the 5, 10, 20 ng/kg cholecystokinin octapeptide injections respectively. The phasic pyloric motor response to 20 ng/kg cholecystokinin octapeptide injection was greater than that to 5 ng/kg (p < 0.05). Basal pyloric pressure increased after 20 ng/kg (1.0 v 0.2 mm Hg, p < 0.05 cf saline). Antral and duodenal pressure waves were suppressed initially by all doses of cholecystokinin (p < 0.05 cf saline). Subsequently, 20 of the 42 cholecystokinin octapeptide, injections but none of the saline injections, were followed by antropyloric pressure waves. Atropine, 15 micrograms/kg iv as a bolus, and then 4 micrograms/kg/hour iv as an infusion, had no effect on the stimulation of localised phasic pyloric pressure waves by cholecystokinin octapeptide 10 ng/kg. It is concluded that stimulation of pyloric contractions and suppression of antral and proximal duodenal motility may contribute to the slowing of gastric emptying produced by cholecystokinin. PMID- 8432449 TI - Impaired IgA response to Giardia heat shock antigen in children with persistent diarrhoea and giardiasis. AB - The serum antibody response in Gambian children with persistent diarrhoea and giardiasis has been studied. Total serum IgG, IgA, and IgM concentrations were increased in these patients as compared with controls from the same area. Determination of the concentrations of Giardia specific antibodies by enzyme linked immuno adsorbent assay (ELISA), however, revealed that only IgM was raised while those of IgA and IgG were similar to the controls. Analysis of the antigenic determinants of the IgG and IgA responses by immunoblotting showed that patients with chronic infection unlike those who clear the infection have no IgA response to a 57 kDa Giardia heat shock antigen. The association of high concentrations of Giardia specific IgM, low concentrations of Giardia specific IgA and IgG and inability to clear the infection suggests that the switch from an IgM to an IgG or IgA response is inefficient. PMID- 8432450 TI - Ischaemic colitis: two distinct patterns of severity. PMID- 8432451 TI - Serum antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease are mainly associated with ulcerative colitis. A correlation study between perinuclear antineutrophil cytoplasmic autoantibodies and clinical parameters, medical, and surgical treatment. AB - Perinuclear antineutrophil cytoplasmic antibodies have recently been demonstrated in the sera of patients with inflammatory bowel disease. Three hundred and sixty six sera obtained from 120 patients with ulcerative colitis, 105 patients suffering from Crohn's disease and 49 non-inflammatory bowel disease controls were tested in two laboratories, using an indirect immunofluorescence assay. In addition, a fixed-neutrophil enzyme linked immunoadsorbent assay (ELISA) was evaluated in one of the two laboratories. The results in the immunofluorescence test showed a high degree of correlation between the two laboratories (Kappa coefficient = 0.8). Ninety five of the 120 (79%) ulcerative colitis patients had a positive test whereas only 14 of the 105 (13%) patients with Crohn's disease were positive. Sera from four patients suffering from primary sclerosing cholangitis were positive as well as four of the 45 control sera (9%). The sensitivity of the perinuclear antineutrophil cytoplasmic antibody immunofluorescence test for the diagnosis of ulcerative colitis was 0.75 with a specificity of 0.88 and a positive predictive value of 0.88 (all sera). In the ELISA technique 37 of 94 ulcerative colitis sera and one of the 68 Crohn's disease sera were positive. In the control group only one of the patients suffering from primary sclerosing cholangitis reacted positively (32 non inflammatory bowel disease sera tested). The ELISA technique had a high specificity (0.97), but a low sensitivity (0.39). There was no relation of perinuclear antineutrophil cytoplasmic antibodies in ulcerative colitis patients or in Crohn's disease patients with disease activity, duration of illness, localisation, extent of disease, previous bowel operations or medical treatment. The clinical significance of perinuclear antineutrophil cytoplasmic antibody positive and negative subsets in both groups of patients thus remains unexplained. Our study confirms that determination of serum antineutrophil cytoplasmatic antibodies in patients with inflammatory bowel disease may differentiate ulcerative colitis from Crohn's disease. Further immunological studies are needed to explain the absence of these antibodies in a subset of ulcerative colitis patients and their role in the pathogenesis of the disease. PMID- 8432452 TI - Adsorbents as antiendotoxin agents in experimental colitis. AB - The intestinal mucosa protects the body from a large reservoir of intraluminal pathogenic bacteria and endotoxins. This mucosal barrier is disrupted by the inflammation and ulceration of inflammatory bowel disease and may permit the absorption of toxic bacterial products. Systemic endotoxaemia has been demonstrated in ulcerative colitis and Crohn's disease and correlates with the extent and activity of disease. In this study the efficacy of absorbents as antiendotoxin agents in a hapten induced rat model of colitis is investigated. Induction of colitis was associated with systemic endotoxaemia. Enteral administration of terra fullonica and kaolin, but not of charcoal, significantly reduced systemic endotoxaemia (terra fullonica 4.2 (1.40) pg/ml; kaolin 5.29 (1.86) pg/ml; charcoal 32.7 (16.6) pg/ml; water 39.8 (12.6) pg/ml). Data expressed as mean (SE). With increasing severity of colitis, there was a decreasing ability of adsorbent therapy (terra fullonica) to control systemic endotoxaemia. Enteral administration of adsorbents controls gut derived systemic endotoxaemia in experimental colitis in animals and may be a useful antiendotoxin treatment in patients with inflammatory bowel disease. PMID- 8432453 TI - Anti-lactoferrin antibodies and other types of ANCA in ulcerative colitis, primary sclerosing cholangitis, and Crohn's disease. AB - Fifty two serum samples from patients with Crohn's disease, 24 from patients with ulcerative colitis, and 12 from patients with primary sclerosing cholangitis were analysed for the presence of anti-neutrophil cytoplasm antibodies (ANCA) of IgG and IgA class by means of enzyme linked immunosorbent assays using lactoferrin, myeloperoxidase, and antigen extracted from azurophil granules, 'alpha antigen' (that is, an antigen preparation containing proteinase 3) as substrates. A high frequency of positive tests for IgG anti-lactoferrin antibodies was found in sera from patients with ulcerative colitis (50%) and primary sclerosing cholangitis (50%). In Crohn's disease only 4 of 52 (8%) sera had anti-lactoferrin antibodies- in all four instances the sera belonged to patients with disease involving the colon. All patients with sclerosing cholangitis and positive tests for anti lactoferrin had ulcerative colitis. Low levels of IgG antibodies against myeloperoxidase or alpha antigen were also found occasionally in sera from patients with ulcerative colitis and primary sclerosing cholangitis. IgA antibodies directed against lactoferrin and alpha antigen (but not myeloperoxidase) were seen in all three conditions. PMID- 8432454 TI - Adhesive and hydrophobic properties of Escherichia coli from the rectal mucosa of patients with ulcerative colitis. AB - The adherent properties and hydrophobicity of Escherichia coli isolates have been compared from the rectal mucosa of patients with active and inactive ulcerative colitis and from a control patient group. Patients with active colitis were colonised less frequently and with lower numbers of E coli than were control patients. Mannose resistant adhesion to HEp-2 cells was determined for 124 isolates of E coli and surface hydrophobicity was estimated by salt agglutination in 96 of these isolates. There was no significant difference in the distribution of adherent strains between the colitis patient groups or with disease activity. E coli from the control patients were marginally less adhesive than those from colitics. The hydrophobicity of isolates did not differ significantly between colitic and control groups nor were there significant differences correlated with disease activity. Furthermore, for these mucosal E coli isolates, hydrophobicity and mannose resistant adhesion were unrelated characteristics. PMID- 8432455 TI - Quantification of disease activity in Crohn's disease by computer analysis of Tc 99m hexamethyl propylene amine oxime (HMPAO) labelled leucocyte images. AB - The reliability and clinical applications of computerised image analysis measurement of bowel uptake of Tc-99m HMPAO labelled leucocytes has been examined as a measure of disease activity in Crohn's disease. In 54 studies carried out on 33 patients with established Crohn's disease, the mean 'scan score', a quantitative assessment of image intensity, was 82.1 SEM (13.6), in patients with clinically active disease compared to 24.7 (7.0) in those with quiescent disease, p < or = 0.0005. A significant correlation was found between the scan score and Crohn's Disease Activity Index (rs = 0.52, p < 0.0001), and Harvey and Bradshaw Simple Index (rs = 0.4, p < 0.004). A low scan score correctly identified seven patients whose raised Crohn's Disease Activity Index incorrectly indicated active disease because symptoms used in calculation of the index were not caused by active inflammation. Of the laboratory measurements, the scan score correlated with the haemoglobin (rs = 0.66, p < 0.0001), albumin level (rs = -0.6, p < 0.0001), C-reactive protein (rs = 0.7, p < 0.0001), alpha-acid glycoprotein (rs = 0.57, p < 0.001), and platelet count (rs = 0.47, p < or = 0.006), but not with the erythrocyte sedimentation rate (rs = 0.2, p < or = 0.25). The scan score was raised in all patients who had clinically active disease but normal laboratory tests. The results of this study indicate that the scan score provides an objective indicator of disease activity in Crohn's disease which may be superior to clinical indices, and also to laboratory tests which although objective are often normal in the presence of active disease. PMID- 8432456 TI - Complications and limitations of injection sclerotherapy in portal hypertension. AB - Injection sclerotherapy is now the accepted first line treatment for bleeding oesophageal varices, although it is associated with an impressive list of rare complications. The main problem concerns the strategy for uncontrollable or recurrent bleeding. Patients with uncontrolled bleeding may be referred for surgery after considerable blood loss and are then extremely difficult to assess. The effects of blood loss on liver function can lead to an unduly pessimistic assessment of liver status. An effective choice of emergency surgical procedure may require considerable surgical expertise. Oesophageal transection and devascularisation are satisfactory for many patients with oesophageal varices secondary to cirrhosis and should nearly always control bleeding. Difficulties arise in patients who are grossly obese and in those who have undergone extensive surgery in the upper abdomen. Problems may also be encountered in those treated by repeated sclerotherapy, which may have caused severe inflammatory change and thickening around the lower oesophagus and upper stomach. We believe that an emergency mesocaval shunt using either a vein graft or a synthetic material such as polytetrafluoroethylene is the procedure of choice for this difficult group of very sick patients. The surgical exposure is satisfactory and not unduly prolonged in even the largest patients and the technique does not interfere with any subsequent transplant operation. There is a greater choice in the management of the patient with less urgent bleeding from recurrent varices after sclerotherapy. Repeat sclerotherapy may be effective for small oesophageal varices while liver transplantation may be indicated in the patient with deteriorating liver function. A selective distal splenorenal shunt should be considered for patients with intact splenic and left renal veins and a mesocaval vein graft for the remainder. We would therefore suggest that surgery should still be considered for the management of portal hypertension, particularly in the following circumstances: (1) Uncontrollable bleeding during the initial course of sclerotherapy; (2) Life threatening haemorrhage from recurrent varices; (3) Bleeding from ectopic varices not accessible to sclerotherapy; (4) Uncontrollable bleeding from oesophageal ulceration secondary to injection sclerotherapy; (5) Severe, symptomatic hypersplenism; (6) For patients who live in communities remote from blood transfusion facilities and adequate medical care. The management of the complications of portal hypertension continues to pose problems. We believe that the best results should come from a combined management approach using injection sclerotherapy as primary treatment and surgery for complications and for haemorrhage from unusual anatomical sites. PMID- 8432457 TI - Plasminogen activators in normal tissue and carcinomas of the human oesophagus and stomach. AB - Carcinogenesis in the human colon is associated with a marked increase of urokinase type plasminogen activator and a decrease of tissue type plasminogen activator. This study was performed to determine the concentrations of urokinase type plasminogen activator and tissue type plasminogen activator in normal tissue and carcinomas along the upper part of the gastrointestinal tract. Activity and antigen levels of both activators were determined in homogenates of endoscopically obtained biopsies from normal and carcinomatous tissues. Although the concentrations of tissue type plasminogen activator and urokinase type plasminogen activator in normal squamous epithelium of the oesophagus were low compared with those in columnar epithelium from the stomach, the urokinase type plasminogen activator/tissue type plasminogen activator antigen ratio of the different locations showed hardly any difference. Significant but heterogeneous increases were found in urokinase type plasminogen activator concentrations of biopsy specimens originating from carcinomas of both epithelial cell types. A decrease in tissue type plasminogen activator concentrations, as found in human colon carcinomas, could only be shown in carcinomas of columnar epithelium origin but not in squamous cell carcinomas of the oesophagus. The increase of urokinase type plasminogen activator and urokinase type plasminogen activator/tissue type plasminogen activator antigen ratio and the decrease of tissue type plasminogen activator in the carcinomas did not show a significant correlation with known prognostic determinants as differentiation grade, TNM classification, intestinal metaplasia, inflammation, and ulceration. The heterogeneous increase of urokinase type plasminogen activator in oesophageal and stomach carcinomas, together with the recently described association of urokinase type plasminogen activator in tissue extracts of breast carcinomas with aggressiveness and prognosis, may be relevance to prognostic studies, may be of relevance to prognostic studies in oesophageal and gastric cancer. PMID- 8432458 TI - Electron microscopic study of intercellular junctions in human gastric mucosa with special reference to their relationship to gastric ulcer. AB - The development of gap junctions in the human gastric mucosa has been examined to see if there is any relation to gastric ulcer. Freeze fracture replicas were prepared from the endoscopic biopsy specimens of 20 patients with gastric ulcer (15 men and five women, aged 49 (13) years) and seven healthy volunteers (four men and three women, aged 41 (19) years). Large fractured areas of lateral cell membranes of surface mucous cells were observed randomly at a direct magnification of 15,000 using electron microscopy. Small gap junctions were observed between gastric surface mucous cells in all healthy volunteers. Gap junctions in the patients with gastric ulcer were significantly fewer than in the healthy volunteers. In addition, gap junctions in patients with recurrent ulcer were significantly fewer than in those with first onset ulcer. There was no obvious relationship between age and the development of gap junctions in patients with gastric ulcer or in healthy volunteers. In areas of intestinal metaplasia, gap junctions were occasionally seen between absorptive cells of the villi, but not in the lateral membranes of goblet cells. These findings suggest that loss of intercellular communication via gap junctions is associated with gastric ulcer formation. PMID- 8432459 TI - Identification of progastrin derived peptides in colorectal carcinoma extracts. AB - The possible production of gastrin by colorectal carcinomas has been studied. Extracts of 44 tumours and adjacent macroscopically normal tissue were examined in radioimmunoassay using the following antibodies: (i) L289 raised to a C terminal fragment of progastrin which shows specificity for intact progastrin, but not the extreme C-terminal tryptic peptide; (ii) LW60 raised to a C-terminal fragment of progastrin which reacts with progastrin and its C-terminal tryptic peptide; (iii) 109-21 which was raised to, and reacts with, Gly-extended forms of heptadecapeptide gastrin--that is, biosynthetic intermediates on the pathway producing active gastrin; and (iv) L2 which reacts with amidated, biologically active gastrins. All samples contained detectable material in assays using LW60; in general, concentrations measured with this antibody were higher than with the other antibodies, and in particular there were higher concentrations in tumour compared with normal tissue extracts. Tumour extracts also contained higher concentrations of immunoreactivity compared with normal tissue, in assays using antibodies L289 and 109-21. In contrast, amidated gastrins were found in similar concentrations in tumour and normal tissue, and concentrations were the lowest of those recorded in the four assays. Separation on Sephadex G50 revealed peaks compatible with progastrin and its C-terminal flanking peptide, and two other peaks that are so far unidentified. In conclusion most colorectal carcinomas contain peptides derived from the gastrin precursor, progastrin, but for the most part these tumours do not convert progastrin into biologically active products. PMID- 8432460 TI - Feasibility of family based screening for colorectal neoplasia: experience in one general surgical practice. AB - Relatives of patients with colorectal cancer have on average a two to threefold increased risk for developing bowel neoplasia although in some families the risk is much higher. This study examined the compliance for endoscopic screening and faecal occult blood testing among first degree relatives of patients with colorectal cancer to determine the feasibility of offering a screening service in a surgical practice. The endoscopic method (flexible sigmoidoscopy or colonoscopy) offered depended upon the extent of family history. Spouses of patients were offered flexible sigmoidoscopy as a group for comparison. Compliance in first degree relatives was significantly higher than in spouses (69% v 47%, p < 0.01) and among those relatives of patients who had died recently from colorectal cancer but time since diagnosis in the index case had no effect. Adenomas were found in 14 of 92 (15%) relatives and three of 30 (10%) spouses. It is estimated that, under our screening guidelines, every 100 patients with colorectal cancer would generate a list of 35-40 relatives who would be screened once by flexible sigmoidoscopy and perhaps 75, who because of their young age, might be screened twice in their lifetime. Also, from this same 100 patients, about 12-15 relatives would merit entry in a colonoscopic screening programme because of their more extensive family history. These results indicate that endoscopic screening of relatives of patients with colorectal cancer is feasible within a practice. PMID- 8432461 TI - Molecular biology and gastric carcinoma. PMID- 8432462 TI - Achalasia cardia: dilatation or operation? PMID- 8432463 TI - Clinical and pathological spectrum of coeliac disease--active, silent, latent, potential. PMID- 8432464 TI - Oesophagitis is as important as oesophageal stricture diameter in determining dysphagia. AB - It is a common observation that stricture patients with severe dysphagia may have a wide lumen, while others with a narrow stricture have few swallowing complaints. In 64 patients with benign oesophageal stricture the dysphagia score (determined by questionnaire and by a test meal both based on nine different items of food scored according to their solidity) was compared with the diameter of the stricture measured radiologically by premeasured barium spheres. There was evidence of an association, but the correlation coefficient (r) was 0.544 (p = 0.0001), suggesting that the diameter of the stricture is an important, although not the sole, determinant of dysphagia. Stricture diameter explains 29.6% (r2) of variation in dysphagia score. The patients (mean dysphagia score 71 of a maximum possible 90) were divided into three groups according to the severity of oesophagitis (19 patients had minimal, 22 moderate and 23 severe oesophagitis). Analysis revealed the mean dysphagia score to be 83, 73, 59 in each group respectively. Dysphagia score of each group was significantly different from the others (Kruskal-Wallis test). Relating the dysphagia score to stricture diameter for each group gives correlation coefficient r = 0.379 (p = 0.110) in the minimal oesophagitis group, r = 0.651 (p = 0.001) in the moderate group, r = 0.583 (p = 0.004) in the severe group. If both diameter and severity of oesophagitis are included then 66.0% of the variation can be explained. It is concluded that the degree of oesophagitis is as important as luminal diameter in determining swallowing ability. PMID- 8432465 TI - Glutathione prevents ethanol induced gastric mucosal damage and depletion of sulfhydryl compounds in humans. AB - Whether parenteral administration of reduced glutathione prevented ethanol induced damage to and depletion of sulfhydryl compounds in the human gastric mucosa was investigated. Ten healthy volunteers underwent endoscopy on three separate occasions. Gastric mucosal damage was induced by spraying 80% ethanol on to the gastric mucosa through the biopsy channel of the endoscope. The gastric mucosal score, total sulfhydryls, glutathione, and cysteine were evaluated in basal conditions and after ethanol administration with and without pretreatment with parenteral glutathione. Glutathione significantly decreased the extent of ethanol induced macroscopic injury to the mucosa of the gastric body and antrum. Glutathione's protective effect is associated with appreciable inhibition of ethanol induced depletion of gastric sulfhydryl compounds. This is the first report of protection against ethanol induced gastric mucosal damage by a sulfhydryl containing agent in humans. PMID- 8432466 TI - Erythromycin effects on gastric emptying, antral motility and plasma motilin and pancreatic polypeptide concentrations in anorexia nervosa. AB - In primary anorexia nervosa, gastric motility is often impaired and ensuing symptoms further discourage eating. Prokinetic agents have been shown to accelerate gastric emptying in affected patients. This study investigated whether emptying of a radiolabelled semisolid 1168 kJ meal and antral contractility were enhanced by intravenous erythromycin. Eight women and two men with anorexia nervosa (21-46 years, 50-75% of ideal body weight) received 200 mg erythromycin or placebo under crossover double blind conditions. Gastric emptying and antral contractility were recorded scintigraphically for 90 minutes. In addition, plasma motilin and pancreatic polypeptide concentrations were determined. With placebo, antral contractions were of regular 3 cycles/minute frequency. With erythromycin, less frequent and partly arrhythmic long duration contractions set in and emptying was accelerated: after 90 minutes, the activity remaining in the stomach was markedly less than with placebo in all patients (Sign test, p < 0.002). Basal motilin and pancreatic polypeptide concentrations were normal and showed a normal response to the meal in all patients. Motilin concentrations decreased slightly more and pancreatic polypeptide concentrations increased markedly more with erythromycin than with placebo, possibly because the meal reached the intestine earlier. In conclusion, erythromycin accelerated emptying markedly and in most patients induced an antral motor activity characterised by long duration contractions occurring at often irregular intervals. PMID- 8432467 TI - Real time ultrasonography of the gastric antrum. AB - This study aimed to evaluate whether serial ultrasound measurements of antral volumes are reproducible and, if so, whether they are representative of the entire gastric contents and reliably measure gastric emptying. The antral volume was measured in man after oral and intragastric administration of known amounts of 5% glucose solutions, and on two separate occasions in the same subjects, after the ingestion of a standardised solid-liquid meal (1050 kcal). Antral volume measurements were performed in both supine and upright positions; inter- and intraobserver measurement errors were also assessed. After ingestion or intragastric administration of equal amounts of liquid, antral volumes determined by ultrasound showed a wide intersubject variability. In each individual subject, however, a linear trend was found between the antral volume and amount of ingested or administered liquid. Intrasubject variability of antral volume measurements was at its minimum in fasting conditions and 300 minutes after ingestion of the solid-liquid meal. Intra- and interobserver variations and whether the patient was erect or supine did not affect measurements of antral volumes. These results support the use of real time ultrasound in determining the gastric emptying time. Results at fasting and 300 minutes after a solid-liquid meal are stable end points of measurement. PMID- 8432468 TI - Conjugation of 1-naphthol in human gastric epithelial cells. AB - The biotransformation of xenobiotics is essential to the maintenance of the body's integrity. Mucosal biotransformation has been well documented in the small and large intestine of animals and humans but whether the gastric mucosa plays a role in detoxifying ingested compounds remains largely unknown. The conjugation of the model phenolic compounds, 1-naphthol, by human gastric epithelial cells was assessed in vitro. Freshly isolated and cultured epithelial cells were prepared from surgical specimens obtained from patients undergoing total gastrectomy for cancer. Cell preparations were incubated with 1- 14C-naphthol over 1 hour and the glucuronide and sulphate conjugates formed were separated by thin-layer chromatography. Conjugation of 1-naphthol was observed with both freshly isolated and cultured cells. In freshly isolated cells, the 1 hour turnover of 1 microM 1-naphthol to its glucuronide and sulphate conjugates averaged 19% and 10% respectively. At higher 1-naphthol concentrations, both types of conjugate were formed at about the same rate, up to saturation (apparent Vmax = 0.07 nmol/mg protein/minute, and apparent Km = 40 microM). In cultured cells, the 1 hour turnover of 1 microM 1-naphthol to its glucuronide and sulphate conjugates averaged 35% and 8% respectively. These results suggest that the human gastric mucosa is a detoxifying organ, and that its role with regard to chemical carcinogenesis and drug first pass metabolism deserves further assessment. PMID- 8432469 TI - Development of a 14C-urea breath test in ferrets colonised with Helicobacter mustelae: effects of treatment with bismuth, antibiotics, and urease inhibitors. AB - A 14C-urea breath test analogous to its clinical counterpart is described for use in ferrets naturally or experimentally infected with Helicobacter mustelae. The test is performed within a sealed glass metabolism chamber through which air is drawn at a constant rate and expired breath collected into sodium hydroxide. Peak 14CO2 production occurred approximately 1 hour after substrate administration. Both inter- and intra-animal responses were highly reproducible, with mean coefficients of variation less than 10%. Other than enhancing peak 14CO2 levels very slightly, fasting had little influence on the response. In infant animals challenged with H mustelae, breath test activity increased linearly with the total count of culturable bacteria isolated from the antrum. Treatment of established infections with colloidal bismuth subcitrate (DeNol) for 4 weeks resulted in clearance of all detectable bacteria but retention of some breath test activity. Subsequent regrowth of bacteria was parallelled by an increase in the breath test response. Inclusion of amoxycillin and metronidazole in the treatment regimen, however, eradicated all the bacteria and almost totally eliminated 14CO2 production. This response parallels the clinically observed suppressive effect on H pylori achieved with bismuth alone relative to the total eradication seen with triple therapy. A single oral dose of the urease inhibitor, flurofamide, inhibited over 90% of the response for at least 24 hours. Acetohydroxamic acid was less effective. These findings suggest that in the ferret H mustelae model, breath test analysis can be a useful, non-invasive alternative to endoscopy for evaluation of agents affecting either growth of the organism or urease activity. PMID- 8432470 TI - Improving the selection of patients for upper gastrointestinal endoscopy. AB - A retrospective study was undertaken to investigate how endoscopies yielding positive findings differ a priori from those yielding negative findings: and how those judged 'helpful' (in the sense of influencing management) differ a priori from those judged 'unhelpful'. A total of 483 patients undergoing endoscopy was sampled and a wide range of data abstracted, including 48 patient characteristics available to the gastroenterologist at the time of the decision to perform endoscopy. Sixty nine per cent of endoscopies were positive. Multivariate statistical analysis identified four variables which taken together were strongly predictive of a positive endoscopy. The resulting mathematical formula correctly predicted the outcome of 76% of endoscopies. Eighty two per cent of the endoscopies were retrospectively classified by the gastroenterologists as helpful. Six variables were strongly predictive of a helpful endoscopy. The corresponding formula correctly predicted the finding of 84% of endoscopies. Comparison of the two analyses shows that the two sets of predictions differ substantially. Thus it is important that decision tools should be based not on the crude distinction between positive and negative, but on the more useful distinction between helpful and unhelpful in influencing management. PMID- 8432471 TI - Culture negative cytotoxin positive stools in community acquired diarrhoea. AB - In a significant proportion of cases of community acquired diarrhoea no recognised pathogen is detected. Verocytotoxin producing Escherichia coli (VTEC) are associated with haemorrhagic colitis and the haemolytic uraemic syndrome but their role in community acquired diarrhoea is not fully understood. Using a method of toxin enhancement in mixed faecal culture, 175 stools negative on culture for recognised pathogens were tested for the presence of cytotoxin and 28% were found to be positive. Nine were neutralised by anti-VT1, 29 by anti-VT2, and eight by neither. No control stool samples yielded any cytotoxin. VTEC should be considered as a causative agent in sporadic community acquired diarrhoea. PMID- 8432472 TI - Concentrations of interleukin 6 and tumour necrosis factor in serum and stools of children with Shigella dysenteriae 1 infection. AB - Serum interleukin 6 (IL-6) and tumour necrosis factor (TNF) were measured in children with dysentery during an epidemic caused by Shigella dysenteriae 1. IL-6 and TNF were also measured in fresh stool filtrates from children with acute gastroenteritis. The median serum IL-6 concentration was raised significantly in the children with complications (haemolytic uraemic syndrome, leukemoid reaction, thrombocytopenia, thrombocytosis, and severe colitis lasting more than one week) during the first week (n = 18, 9-7728 pg/ml; median 107) and in the second week (n = 13, 5-312 pg/ml; median 77), compared with convalescent sera (n = 10, < 3-85 pg/ml; median 39; p < 0.02 and < 0.05 respectively). The median IL-6 concentration during the first week was significantly higher in the group with complicated disease than in those with no complications (n = 8, < 3-37 pg/ml; median 5; p < 0.001). Although serum TNF concentrations were significantly raised in the complicated group during the first and second weeks of the illness and in the uncomplicated group compared with convalescence, there was no significant difference in the TNF concentrations between the complicated and uncomplicated groups. IL-6 was detectable in stool filtrates from eight of 13 children with S dysenteriae 1 infection and four of eight children with S flexneri infection. It was not detectable in Cryptosporidia, rotavirus, or adenovirus infections, those with pathogen-negative acute diarrhoea or controls. Seven of 13 children with S dysenteriae 1 and three of nine children with S flexneri infections had TNF detectable in stools. None of the children with Salmonella, Cryptosporidia, rotavirus of children with pathogen-negative diarrhoea and controls had detectable TNF in stool filtrates. It is postulated that the local and generalised vasculitis observed in shigellosis may be related to a direct effect of Shiga toxin on endothelial cells or caused by cytokine production stimulated by endotoxin, or both. PMID- 8432473 TI - Antineutrophil antibody: a test for autoimmune primary sclerosing cholangitis in childhood? AB - The detection of an antineutrophil antibody which is highly sensitive and specific for adult primary sclerosing cholangitis using indirect immunoalkaline phosphatase has been previously described. In this study, the diagnostic potential of this method in childhood primary sclerosing cholangitis is described. A range of 72 blinded children's sera (36 boys), aged six months to 21 years (10 primary sclerosing cholangitis, eight autoimmune chronic active hepatitis, 10 alpha-1 antitrypsin deficiency, 12 extrahepatic bile duct atresia, 11 ulcerative colitis and 21 normal subjects) was assayed. Eight of the 10 primary sclerosing cholangitis patients were correctly identified. Three patients with chronic active hepatitis also showed the characteristic primary sclerosing cholangitis pattern of staining. No ulcerative colitis patients or any other patients showed this pattern of staining. All normal subjects were negative. As in adult primary sclerosing cholangitis, there is a specific antineutrophil antibody in childhood primary sclerosing cholangitis and this provides further evidence towards an autoimmune aetiology of this condition. The test may have diagnostic potential. PMID- 8432474 TI - Transfer of cow's milk beta-lactoglobulin to human serum after a milk load: a pilot study. AB - A sensitive and specific enzyme linked immunosorbent assay (ELISA) was developed for the quantification of cow's milk beta-lactoglobulin in human serum. The assay had a sensitivity of 80 pg/ml (2 standard deviations from zero) and did not cross react significantly with any other tested milk proteins. The absorption of cow's milk beta-lactoglobulin and beta-lactoglobulin immunoglobulin G antibody levels after a milk load was investigated in eight healthy non-allergic individuals. There was a significant variation in the circulating beta-lactoglobulin antigen levels during the six hour period after feeding (p < 0.01) for the combined data. A biphasic absorption pattern was seen in all subjects except one subject who had undetectable levels. No significant variation with time was observed for the beta lactoglobulin IgG antibody levels and no correlation was found between the beta lactoglobulin antigen levels and the beta-lactoglobulin IgG antibody levels. This pilot study offered information on the quantity of immunogenic cows' milk protein transferred to the blood after a milk load in non-allergic healthy adults and confirmed a biphasic profile of antigen transfer. The sensitivity of the assay used has shown that transfer of food antigen does occur in the majority of healthy nonallergic subjects. PMID- 8432475 TI - Numbers of T cell receptor (TCR) alpha beta+ but not of TcR gamma delta+ intraepithelial lymphocytes correlate with the grade of villous atrophy in coeliac patients on a long term normal diet. AB - Numbers of T cell receptor (TcR) gamma delta+ and alpha beta+ intestinal lymphocytes were studied in 34 coeliac patients in respect of their diet and the grade of villous atrophy. Particular attention was given to a group of 21 patients with coeliac disease according to ESPGAN criteria who were on a well tolerated long term normal diet and in nine of whom the mucosa had returned to normal or nearly normal. A significant increase in TcR gamma delta+ cells was observed in the gut epithelium of coeliac patients compared with age matched controls, and this did not correlate with either the presence of gluten in the diet or with the grade of villous atrophy. Thus, numbers of TcR gamma delta+ intraepithelial lymphocytes (IEL) were considerably above the normal range in four of seven patients on a gluten free diet and in four of nine patients who had recovered a normal or nearly normal mucosa in spite of a normal diet. In contrast, numbers of intestinal TcR alpha beta+ cells varied with the stage of the disease. Their number was high in the epithelium of patients with active coeliac disease (n = 18) but significantly less in patients whose mucosa had returned to normal or nearly normal either after gluten free diet (n = 7) or in spite of a normal diet (n = 9). Immunohistochemical markers of intestinal mononuclear cell activation detected in active coeliac disease were either weakly expressed or absent in the latter patients. It is suggested that TcR alpha beta+ but not TcR gamma delta+ IEL are sensitised to gliadin in coeliac disease, and that only the former cells play a direct part in the pathogenesis of the villous atrophy. The normal counts of TcR alpha beta+ IEL and the absence of detectable mononuclear activation in the biopsy specimens of a few patients who have recovered clinical and histological tolerance to gluten sustains this hypothesis and also suggests that immunological tolerance to gluten may be acquired in a subgroup of coeliac patients. Hte appreciable increase in TcR gamma delta+ IEL observed in some of the latter patients, however, is similar to that observed in latent coeliac disease urging for their careful and prolonged follow up until the role of TcR gamma delta+ IEL in the pathogenesis of coeliac disease is elucidated. PMID- 8432476 TI - Abnormal visceral autonomic innervation in neurogenic faecal incontinence. AB - Changes of denervation in the anal sphincter striated and smooth muscle in patients with neurogenic faecal incontinence are well established. This study aimed to determine if there is also a more proximal visceral autonomic abnormality. Thirty women with purely neurogenic faecal incontinence (prolonged pudendal nerve latencies and an intact sphincter ring) and 12 patients with neuropathic changes together with an anatomical disruption were studied. Two control groups consisted of 18 healthy volunteer women and 17 women with normal innervation but an anatomically disrupted sphincter. Rectal sensation was assessed using balloon distension and electrical mucosal stimulation, and anal sensation by electrical stimulation. Rectal compliance was studied to determine whether sensory changes were primary or caused by altered rectal wall viscoelastic properties. Anal canal pressure changes in response to both rectal distension and rectal electrical stimulation were measured to assess the intrinsic innervation of the internal anal sphincter. Patients with neurogenic incontinence alone had impaired rectal sensation to distension (53.1 v 31.5 ml, p < 0.05, neurogenic v controls) and to electrical stimulation (24.4 v 14.8 mA, p < 0.005). Patients with neurogenic incontinence and sphincter disruption also showed impaired sensation compared with healthy controls (55.8 ml v 31.5 ml, p < 0.05 and 22.9 mA v 14.8 mA, p < 0.05). Patients with only a disrupted sphincter had normal visceral sensation to both types of testing. Both rectal compliance and the response of the internal anal sphincter to rectal distension and electrical stimulation were normal in all patient groups. This study suggests that there is a visceral sensory abnormality in patients with neurogenic incontinence which is not caused by altered rectal compliance. As evaluated in this study the intrinsic innervation of the internal anal sphincter is not affected in this process. PMID- 8432477 TI - Does the ileocolonic junction differentiate between solids and liquids? AB - Previous observations from our laboratory have suggested that colonic filling from the ileum is characterised by a series of bolus movements. The present experiments were designed to test the hypothesis that bolus transit of ileal contents into the colon would not distinguish between solids and liquids. After a manometric infusion assembly was positioned by mouth into the ileum of 13 healthy volunteers, a mixture of nutrients (75 kcal), incorporating a solid phase radiolabel (111In labeled resin pellets) and a liquid phase marker (99mTc-DTPA), was infused into the ileum. Transit of both labels from the ileum to colon was quantified scintigraphically and ileal motility was also recorded. When markers were infused into the proximal ileum, 100 cm proximal to the ileocolonic junction (six), there were clear cut examples of discriminant transit, when liquids moved more rapidly from the small to the large bowel than did solids. When isotopes were instilled into the distal ileum, less than 50 cm from the ileocolonic junction, no separate transit of the solid and liquid phases was observed. No specific motor pattern of the ileum was regularly associated with bolus filling of the colon. These results support the hypothesis that the distal ileum can discriminate between solids and liquids but that the ileocecal junction cannot. PMID- 8432478 TI - Haemoccult does not reduce the need for colonoscopy in surveillance after curative resection for colorectal cancer. AB - Patients who had undergone curative resection for colorectal cancer were studied to compare the efficacy of faecal occult blood detection (Haemoccult test) with colonoscopy in the detection of metachronous tumours. Fifty nine patients were studied and both Haemoccult testing and colonoscopy were successfully completed in 54 patients. In 37 patients, both tests were negative. One patient with a positive Haemoccult test had no colonoscopic abnormality and remains alive and well two years later. There were, however, 16 patients with negative Haemoccult tests in whom an abnormality was found on colonoscopy. In four patients, one Dukes's A cancer and seven tubulovillous adenomas were found--all neoplastic lesions that would have been missed if surveillance had been by Haemoccult alone. PMID- 8432479 TI - DNA ploidy in early gastric carcinoma (T1): a flow cytometric study of 100 European cases. AB - DNA ploidy of 100 early gastric carcinomas (T1) was analysed by flow cytometry on archival material from five European centres and was correlated to morphological features and clinical behaviour. Tumours were classified according to the macroscopic appearance, histological type, and growth pattern. Aneuploidy was observed in 39% of tumours. Aneuploidy was more frequent in submucosal than in mucosal tumours (p = 0.04), in raised than in flat or ulcerated lesions (p = 0.001), and in the intestinal histological than in the diffuse types (p = 0.016). The presence of lymph node metastasis in 10 cases had no obvious relation to DNA ploidy. Five related deaths occurred during the follow up (6 months--16 years) of 84 patients. These results are similar to those reported in a large Japanese series suggesting no major differences between the two populations. Although follow up data were insufficient to relate DNA ploidy to tumour behaviour in this study, the Japanese experience shows that particular attention should be paid to early direction and complete surgical excision of raised intestinal type T1 carcinomas that have a Pen A growth pattern and are aneuploid. PMID- 8432480 TI - Evaluation of a proposed technique to assess unscheduled DNA synthesis and genotoxicity. AB - Results from a recent, new assay suggest that omeprazole, a potent inhibitor of gastric acid secretion, is genotoxic. The principle of this assay is that the non proliferating zone of surface gastric epithelial cells can be selectively removed by controlled digestion so that any incorporation of tritiated thymidine into these cells represents unscheduled DNA synthesis. Parietal cells (which are located below the uppermost proliferating cells) and proliferating cells in semiconservative, regular DNA synthesis could always be shown in the digested fraction, and as regular DNA synthesis takes up a thousand fold more thymidine than unscheduled DNA synthesis, any signal from unscheduled synthesis would therefore be swamped. The digestion process was also uneven, as histological analysis showed denuded patches of mucosa, and gland like structures were seen in the digest. Quantification of the number of silver grains over the nuclei showed no increase in low level labelling after omeprazole administration, indicating that there was no unscheduled DNA synthesis. The labelling index of undigested gastric tissue from omeprazole treated rats was not significantly different from that of the control group, despite an increase in the plasma gastrin value. PMID- 8432481 TI - Ulcerative colitis disease activity following treatment of associated primary sclerosing cholangitis with cyclosporin. AB - Thirty five adult patients with precirrhotic primary sclerosing cholangitis were randomly allocated to treatment for at least one year with low dose (4.1 mg/kg/day) cyclosporin or placebo in a double blind trial. Thirty patients had coexisting ulcerative colitis, including three who had previously undergone colectomy and one who discontinued treatment after three months. Of the remaining 26 patients, 16 received cyclosporin and 10 received placebo. Endoscopy was performed at entry to confirm the diagnosis of inflammatory bowel disease. The ulcerative colitis disease activity was prospectively classified annually as remission/mild, moderate, or severe using the Truelove and Witt's criteria. Before treatment there were no differences between the cyclosporin and placebo groups in the number of patients with remission/mild colitis, 14/16 (88%) v 9/10 (90%), and moderate colitis, 2/16 (12%) v 1/10 (10%). During treatment, a remission/mild disease course was present in 15/16 (94%) v 6/10 (60%), p = 0.05 and a moderate disease course in 1/16 (6%) v 4/10 (40%), p = 0.05. It is concluded that patients treated with cyclosporin for primary sclerosing cholangitis who have coexisting ulcerative colitis have a more benign course of colitis resulting both from improvement of moderately active colitis and from fewer flares of remission/mildly active colitis. These findings suggest that cyclosporin may be of benefit to the colon in patients with ulcerative colitis who are being treated with cyclosporin for primary sclerosing cholangitis. PMID- 8432482 TI - Thromboembolism in inflammatory bowel disease: role of platelets. AB - Patients with inflammatory bowel disease are susceptible to thromboembolism and recently small vessel thrombosis has been implicated as an aetiological factor in Crohn's disease. This study therefore investigated platelet function in 104 patients with inflammatory bowel disease of whom eight had previous thromboembolism. Thirty five patients had reproducible spontaneous platelet aggregation of more than 30% (0 in controls) (p < 0.0001). A further 20 patients showed hypersensitivity of platelets to low concentrations of aggregating agents (p < 0.001). Plasma thromboxane B2 and beta thromboglobulin levels were significantly higher than controls (p < 0.001 and p < 0.001), but platelet lifespan studies were normal. There was no correlation with disease activity. Patients with inflammatory bowel disease have abnormal platelet activity, which may contribute to the inflammatory process. PMID- 8432483 TI - Human colonic intraepithelial lymphocytes suppress in vitro immunoglobulin synthesis by autologous peripheral blood lymphocytes and lamina propria lymphocytes. AB - Human colonic intraepithelial lymphocytes have been shown to suppress the proliferation of autologous lamina propria lymphocytes and allogeneic peripheral blood mononuclear cells. This study has shown that, in vitro, intraepithelial lymphocytes suppress IgA and total immunoglobulin synthesis (but not IgG or IgM production) by autologous peripheral blood and lamina propria lymphocytes. This down regulation of IgA production is mediated by a soluble factor secreted by the intraepithelial lymphocytes. There is no difference in immunoglobulin down regulation by intraepithelial lymphocytes of control subjects and patients with inflammatory bowel disease. PMID- 8432484 TI - Effect of octreotide on gall stone prevalence and gall bladder motility in acromegaly. AB - Octreotide therapy in acromegaly is associated with an increased prevalence of gall stones, which may be the result of an inhibition of gall bladder motility. Gall stone prevalence in untreated acromegalic patients relative to the general population is unknown, however, and the presence of gall stones and gall bladder motility in these patients and in acromegalic patients receiving octreotide was therefore examined. Thirty four percent of 39 patients who had taken octreotide for a mean of 20 months had gall stones compared with 16% of 38 patients who had not been treated with octreotide (p < 0.005). In a subgroup of 21 patients studied prospectively over 4 to 18 months, two patients developed stones. No patient had symptoms referrable to their gall stones. In 31 untreated acromegalic patients, the mean fasting gall bladder volume was similar to that in normal subjects. Maximal percentage emptying, however, was impaired (34 v 64%, p < 0.001) and the mean postprandial residual gall bladder volume increased (21.7 v 9.0 ml, p < 0.001). Treatment with octreotide increased the mean postprandial residual volume further to 36.8 ml (p < 0.001). Gall bladder emptying in untreated acromegalic subjects is impaired. Octreotide further increases postprandial residual gall bladder volume and this may be a factor in the increased gall stone prevalence seen in these patients. PMID- 8432485 TI - Results of extracorporeal shock wave lithotripsy of gall bladder stones in 693 patients: a plea for restriction to solitary radiolucent stones. AB - During a period of 24 months 693 consecutive patients with symptomatic gall bladder stones (526 males, 167 females; mean age 51 years, range 18-89) were treated by extracorporeal shock wave lithotripsy with a Piezolith 2300. The procedure was carried out on an out-patient basis without analgesics or sedatives. Concomitant chemolitholytic treatment (ursodeoxycholic and chenodeoxycholic acid 7.5 mg/kg/day each) was administered until three months after total fragment clearance for a maximum therapy period of 1.5 years. In 601 patients with radiolucent stones complete clearance of all fragments was obtained after three, six, 12, and 18 months in respectively 20, 41, 64, and 78%. Actuarial analysis of the subgroups according to the stone mass (size and number) selected an ideal patient population with solitary stones less than 20 mm diameter (84% stone free after one year). The results are significantly less good when the greater the number of stones or their maximal diameter increases. Treatment was interrupted in 3.6% of the patients. In 90 sludge or fragments remain present. Twenty five patients were lost to follow up for non-biliary reasons. Stone recurrence was 5.7% at one year and was observed both in patients with solitary and multiple stones. A cost effectiveness analysis suggests that laparoscopic cholecystectomy is the most effective and economic solution, although extracorporeal shock wave lithotripsy for solitary radiolucent stones less than 2 cm is cheaper than conventional cholecystectomy. Extracorporeal shock wave lithotripsy for multiple stones is the most expensive and least effective option. PMID- 8432486 TI - Familial visceral myopathy associated with a mitochondrial myopathy. AB - A 27 year old man with intestinal pseudo-obstruction who developed parenteral nutrition induced hyperlipidaemia and who also had ophthalmoplegia and an undifferentiated myopathy is described. Histological examination of biopsy specimens and molecular analysis show that this patient had both familial visceral myopathy and a mitochondrial myopathy, suggesting that a mitochondrial DNA mutation is the molecular lesion in familial visceral myopathy. PMID- 8432487 TI - Consultant staffing and career prospects in gastroenterology for England and Wales. Royal College of Physicians Committee for Gastroenterology and Clinical Services Committee of the British Society of Gastroenterology. PMID- 8432488 TI - von Willebrand factor in upper gastrointestinal tract inflammation. PMID- 8432489 TI - Nasal oxygen during endoscopy. PMID- 8432490 TI - A call to advocacy. PMID- 8432491 TI - Managing psychotic symptoms when the diagnosis is unclear. PMID- 8432492 TI - Smoking deterrence using silver acetate. PMID- 8432493 TI - Monitoring plasma level of haloperidol in schizophrenia. PMID- 8432494 TI - Criteria for hospital admission. PMID- 8432495 TI - Pharmacological and behavioral treatments for aggressive psychiatric inpatients. AB - OBJECTIVE: Because aggressive behaviors of psychiatric patients may be caused by environmental or biological factors, treatment plans that incorporate medication and behavior therapies are the most effective. The authors review research on pharmacological and behavioral treatments for aggressive patients and present a decision tree for use on behavioral units to direct treatment of such patients. METHODS: The empirical literature was searched for studies of pharmacological and behavioral interventions that have been shown to have some value for treating this problem. RESULTS AND CONCLUSIONS: Psychiatrists must proceed cautiously because no medication has been approved by the Food and Drug Administration specifically for treatment of aggression. Antipsychotics, lithium, antidepressants, sedatives, anxiolytics, anticonvulsants, opiate antagonists, and beta blockers have been used, often depending on the etiology of the aggression, such as head injury or dementia. Although some drugs such as buspirone and propranolol show promise; side effects must be monitored. Three behavioral strategies have effectively reduced aggression in the inpatient milieu. The token economy is perhaps the most comprehensive behavioral tool for producing a well structured milieu. Aggression replacement strategies help patients learn alternative responses. Decelerative techniques teach strategies that enable the patient to reduce aggression quickly. The authors describe a decision tree to guide decisions about pharmacological and behavioral treatments of aggression depending on where in the course of the disorder patients exhibit difficulty. PMID- 8432496 TI - Diagnostic issues in self-mutilation. AB - OBJECTIVE: Pathological self-mutilation--the deliberate alteration or destruction of body tissue without conscious suicidal intent--was examined both as a symptom of mental disorders and as a distinct syndrome. METHODS: Data from more than 250 articles and books were reviewed, as well as data obtained by the authors from their extensive clinical experience in treating self-mutilating patients. RESULTS AND CONCLUSIONS: The diverse behaviors that constitute pathological self mutilation can be categorized into three basic types: major--infrequent acts that result in significant tissue damage, usually associated with psychoses and acute intoxications; stereotypic--fixed, rhythmic behavior seemingly devoid of symbolism, commonly associated with mental retardation; and superficial or moderate--behavior such as skin cutting, burning, and scratching associated with a variety of mental disorders. The authors propose that a syndrome of repetitive superficial or moderate self-mutilation should be regarded as an axis I impulse disorder. In most cases, the syndrome coexists with character pathology. PMID- 8432497 TI - Treating revolving-door patients who have "hospitalphilia": compassion, coercion, and common sense. AB - Treatments applicable to the frequently rehospitalized psychiatric patient--the so-called revolving-door patient--have been poorly delineated. One subgroup of these patients includes those for whom recidivism has become a way of life; they may be said to suffer from "hospitalphilia." Neither refractoriness to treatment nor noncompliance with medications explains their frequent admissions. The author presents ten clinical principles to guide treatment planning for this subgroup of patients. The principles emphasize cooperation between the patient and the treatment agencies in creating a comprehensive, consistent, and enforceable plan to reduce unnecessary hospitalizations. Four treatment strategies based on the principles are outlined: unlimited access to hospitalization, a chit or voucher system, a rationing system, and an approach centered on the patient's expressed ability to avoid hospitalization. PMID- 8432498 TI - Therapeutic use of conservatorship in the treatment of gravely disabled psychiatric patients. AB - In California conservatorship is a legal mechanism that allows an individual or agency (the conservator) to act on behalf of a gravely disabled mentally ill person (the conservatee) to determine what arrangements are necessary to provide adequate food, clothing, shelter, and treatment, including hospitalization when indicated. Conservatorship can play an important role in clinical management and treatment, particularly if the gravely disabled person does not have close family involvement and support, as case histories indicate. The benefits of conservatorship can be greatly enhanced by combining it with case management. When family members are appointed as conservators, skilled clinical staff can help them use the leverage of conservatorship therapeutically. By giving up some of their freedom, many conservatees who would ordinarily need to be hospitalized for long periods are able to retain most of their independence and their community status. PMID- 8432499 TI - The cost of accreditation: one hospital's experience. AB - OBJECTIVE: The 1989 survey conducted by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) at the UCLA Neuropsychiatric Hospital was the hospital's first using standards outlined in the 1989 edition of JCAHO's Accreditation Manual for Hospitals. The authors' goal was to calculate the cost of preparing for and undergoing the 1989 survey. METHODS: Costs associated with planning for the survey and conducting a mock survey and the actual survey were based on records of staff time spent on those activities, fees for consultant services, and fees for the actual survey. Costs associated with follow-up of the mock survey, preparation for the actual survey, and additional staff time spent in record keeping and treatment planning to meet accreditation standards were based on staff estimates of time spent in these activities. RESULTS: Documented and estimated costs for the survey process totaled $326,784, which represented about 1 percent of the hospital's operating budget for 1989. CONCLUSIONS: Although the hospital had a successful survey outcome and received accreditation with few contingencies, the authors question whether quality of care was improved by the survey process and whether the high cost of the survey constitutes an appropriate use of resources. PMID- 8432500 TI - Patient dumping, COBRA, and the public psychiatric hospital. AB - Serious clinical and risk management problems arise when indigent patients with acute medical conditions are transferred from general medical hospitals or emergency departments to public psychiatric hospitals that are ill equipped to provide medical care. To combat such practices, referred to as dumping, Congress included measures in the Consolidated Omnibus Budget Reconciliation Act of 1985 (COBRA) prohibiting such transfers. Because physicians and administrators in public psychiatric hospitals are generally not aware of the potential usefulness of COBRA in reducing dumping, this paper describes its important provisions. The key to preventing dumping is to educate referral sources to limitations on the medical care available at the receiving hospital and to discourage negligent patient transfers by enforcing COBRA. Public hospital staff and legal counsel who become familiar with COBRA's provisions can develop an antidumping strategy. PMID- 8432501 TI - Personality disorders diagnosed at intake at a public psychiatric facility. AB - OBJECTIVE: The purpose of the study was to determine the prevalence of personality disorders among a large population of persons seeking treatment in a public psychiatric facility and to examine the role of personality disorders in the clinical conditions of persons frequenting such facilities. METHODS: Clinical and demographic data were retrospectively examined for 18,179 adults who visited a walk-in clinic of a public psychiatric facility between 1983 and 1989. Patients who received a diagnosis of personality disorder were compared with those who did not. RESULTS: A total of 2,344 patients (12.9 percent) were diagnosed as having a personality disorder, a lower prevalence rate than generally found in treatment populations. The most frequent diagnoses were atypical, antisocial, and borderline personality disorders. Compared with other subjects, those with a personality disorder were significantly more likely to be men, to be 35 years old or younger, to have a higher level of social impairment, and to have more symptoms and more severe symptoms. CONCLUSIONS: The relatively low prevalence rate was attributed in part to underdiagnosis, largely due to the need for making rapid assessments in a public intake setting. The authors conclude that clinicians in such facilities may be likely to diagnose personality disorders when patients with certain axis I disorders such as substance use, affective, and adjustment disorders present with an overall greater level of symptomatology and social impairment. PMID- 8432502 TI - Resilience in adversity among long-term survivors of AIDS. AB - OBJECTIVE: This study evaluated psychological and behavioral aspects of quality of life and medical care utilization in a population of gay men whose intake records at a New York City agency indicated the presence of an AIDS-defining opportunistic infection at least three years before entry into the study. METHODS: Fifty-three men participated in a standardized psychiatric assessment of current mood disorders, psychiatric distress, future outlook, quality of life, and physical functioning using several clinician- and self-rated scales and a semistructured interview. RESULTS: Almost all of the men had experienced more than one episode of life-threatening illness, and many had been led to believe that they had only months to live. Nevertheless, low rates of current syndromal mood disorders and psychiatric distress were found. Degree of physical impairment was unrelated to psychiatric distress or life satisfaction, although men with more limited physical function were less optimistic about the future. CONCLUSIONS: Nearly all study participants displayed an extraordinary psychological resiliency and shared the conviction that good times lay ahead and that life continued to be worthwhile. PMID- 8432503 TI - Changes in health and job attitudes of case managers providing intensive services. AB - OBJECTIVE: The health, personal life, and attitudes of case managers providing intensive services to severely mentally ill clients were evaluated to see how the managers changed over their first 18 months on the job. The authors report here on changes on major variables related to health status and job attitudes. METHODS: A cohort of 82 case managers newly hired during the first year of New York State's intensive case management program was followed for 18 months. A battery of measures of health, life events, life satisfaction, social support, job situation, and job attitude was administered by mail questionnaire at job entry and at three, 12, and 18 months to case managers who remained employed in the program. RESULTS: Approximately 80 percent of the eligible (still-employed) case managers responded at each time point; 64 were still employed at the end of the study. Over time they experienced increasing amounts of job stress and emotional exhaustion, depersonalized clients more, and reported significantly more stress-related physical symptoms and depressive symptoms. However, their sense of personal accomplishment and their job satisfaction remained stable. CONCLUSIONS: Case managers appeared able to overcome job pressures and persevere in their professional commitment. What difficulties they had appeared to level off after one year, at least among those who continued in their positions. Although the findings do not indicate that case managers need intensive help, early support and preventive intervention for job difficulties would be helpful. PMID- 8432504 TI - Cocaine use by schizophrenic outpatients who receive depot neuroleptic medication. PMID- 8432505 TI - Criminal activity by psychiatric clients after hospital discharge. PMID- 8432506 TI - An in-home crisis intervention program for children and their families. PMID- 8432507 TI - Polydipsia and hyponatremia. PMID- 8432508 TI - AIDS and child sexual abuse. PMID- 8432509 TI - Pathogenic significance of interleukin-6 in angioimmunoblastic lymphadenopathy type T-cell lymphoma. AB - Patients with angioimmunoblastic lymphadenopathy (AILD)-type T-cell lymphoma may develop hypergammaglobulinemia. Among four cases of AILD-type T-cell lymphoma that we have studied, we detected a correlation between the number of plasma cells in tissue and the extent of interleukin-6 (IL-6) expression in lymphoma cells. We did not detect IL-6 in three patients who had no hypergammaglobulinemia and whose tissues showed only minimal plasma cell infiltration. In the fourth patient we observed an abundant IL-6 production by lymphoma cells, which accounted for a B-cell plasmacytic tissue response and for hypergammaglobulinemia. The pathogenic significance of IL-6 was substantiated by a concomitant decrease in the serum IL-6 level, measurable tumor mass, and immunoglobulin levels, as well as by a decline in the proportion of plasmacytoid cells in peripheral blood promptly on administration of chemotherapy. Plasmacytoid B cells could be maintained in culture in the presence of IL-6, but viability was lost on co-incubation with anti-IL-6. Interleukin-1 and tumor necrosis factor were not produced by T lymphoma cells and were incapable of sustaining plasmacytoid B-cell viability in vitro. Small amounts of IL-4 were noted in T lymphoma cells. Thus, in this case of AILD-type T-cell lymphoma, tumor cells with a T-cell phenotype produced IL-6 in large quantities, explaining the accompanying B-cell and plasmacytic histologic changes and humoral disease manifestations, including marked hypergammaglobulinemia. Although not all cases of AILD-type T-cell lymphoma have an accompanying plasma cell proliferation and hypergammaglobulinemia, and although the cytokine network in these patients may be more complex than has been recognized, this case with IL-6 expression serves to illustrate the utility of cytokine assays in the analysis of the histopathologic and clinical heterogeneities of peripheral T-cell lymphomas. PMID- 8432510 TI - Morphometric differentiation between responsive tumor cells and mesothelial hyperplasia in second-look operations for ovarian cancer. AB - We developed a procedure based on computerized image analysis to establish objective criteria for the differential diagnosis between mesothelial hyperplasia and cancer in peritoneal tissue samples obtained at second-look operations for ovarian cancer. The tumor tissue after chemotherapy was classified as "nonresponsive" if it was found by histologic criteria to be roughly similar to the tumor before chemotherapy and as "responsive" if it was found to be different (small clusters of bland-looking cells with no mitotic activity). Eighty-five samples of tissue had been classified previously by a pathologist into one of the four following groups: ovarian tumor prior to chemotherapy, "responsive" tumor, "nonresponsive" tumor, or mesothelial hyperplasia. Cell profiles of the tissue samples were studied by computerized image analysis using 21 morphometric descriptors derived from the manual tracings of tumor nuclei, including nuclear perimeter, nuclear area, maximal chord, circularity factor, and standard deviations of these descriptors. Size distribution curves of nuclear areas and maximal chords were included in the analysis. A multivariate discriminant analysis confirmed the separation into the four diagnostic groups, accomplished with consideration of the physical descriptors alone, except for some overlapping between groups 1 and 3. The separation between carcinoma and mesothelial hyperplasia was clear in all cases. PMID- 8432511 TI - Pathology of the pancreas in bone marrow transplant patients. AB - Review of 51 autopsy cases of patients receiving high-dose chemotherapy followed by bone marrow transplantation revealed a high prevalence of pancreatic ductal and acinar changes compared with control groups. Forty-five percent (23 of 51) of bone marrow transplant cases had squamous metaplasia of the pancreatic ducts compared with 10% of randomly selected control cases. Although squamous metaplasia was more common in bone marrow transplant patients receiving chemotherapy, it was not associated with whole body radiation, allogeneic transplantation, or specific drugs. Squamous metaplasia was more common in patients dying 30 days or more after transplantation. Dilatation of the pancreatic acini was present in 78.4% of transplant cases, 35.0% of control cases, and 50.0% of a group of 12 breast cancer patients treated with conventional doses of chemotherapy without bone marrow transplantation. This lesion was associated with uremia. Oncocytic change of the acinar epithelium was present in 52.9% of transplant cases, no control cases, and 41.7% of breast cancer cases. Squamous metaplasia of the pancreas is common in bone marrow transplant patients receiving high-dose chemotherapy and may be a late manifestation of toxic injury to the ducts. A high prevalence of acinar dilatation was associated with terminal uremia. Oncocytic change of acinar epithelium was associated with chemotherapy. PMID- 8432512 TI - The vascular pathology of human hepatic allografts. AB - Studies of hepatic transplant vasculopathy (TV) have described arterial lesions in selected cases but have not sought to establish the relative prevalence of various arterial and venous lesions. We examined 20 unselected liver allografts and 12 controls to establish the spectrum and distribution of transplant-related arterial and venous lesions. Sections of 1,175 arteries and 936 portal and hepatic veins were reviewed and several histologic parameters were tabulated. Fibrotic (18 cases: 184 arteries and 17 veins) and cellular (10 cases: 353 arteries and 33 veins) lesions were seen. Three allografts had evidence of severe TV with abundant foam cell, myointimal, and mixed fibrocellular lesions in the intima of arteries. These three grafts also had foam cells in portal veins. Allografts with TV had more stenotic arteries (P < .05) and more intimal cellular proliferation (P < .05) compared with non-TV allografts and with controls. Foam cells often demonstrated immunoperoxidase staining for actin, lysozyme, or UCHL 1. Two of the TV cases had marked paucity of bile ducts and required retransplantation. PMID- 8432513 TI - Pathologic features of the ureteroileal anastomosis in ileal conduits in childhood. AB - Ileal conduit urinary diversions are associated with a high incidence of late complications often requiring major revision surgery. Although the etiology of the late complications is not always clear, there may be unilateral or bilateral hydroureteronephrosis, with the conduits showing narrowing and stricture formation with villous atrophy, chronic inflammation, and fibrosis. Histologic review of 20 ureteroileal anastomoses from 12 patients showed variable degrees of chronic changes. In addition, cystically dilated intestinal glands were noted in six anastomoses, transitional epithelial-lined cysts were noted in nine, aggregated pools of mucus were noted in four, mixed transitional and intestinal epithelial-lined cysts were noted in two, and polypoid lesions with mucus pools or cysts projecting into the lumen were noted in five. Twelve cysts measured over 1 mm in diameter; six measured over 2 mm. These histologic features may result from overgrowth of intestinal glands by transitional epithelium, with subsequent gland dilatation, rupture, and mucus pooling. It is possible that the larger "cysts" and "polyps" may have contributed to the ureteroileal obstruction, a finding that may have bearing on other types of urinary tract reconstructions using bowel segments. PMID- 8432514 TI - Autopsy findings and clinical diagnoses: a review of 1,000 cases. AB - The protocols of 1,000 consecutive adult patients autopsied during the period June 1983 to December 1988 were retrospectively analyzed and the findings were compared with clinical diagnoses. The autopsy rates during this period ranged between 23% and 27% of hospital deaths. Eighty-seven percent of the autopsied patients were between 15 and 59 years of age. Major discrepancies between the autopsy reports and the clinical diagnoses were present in 31.7% of all autopsy reports reviewed. Infectious diseases were the most common cause of death (46.8%), followed by cardiovascular diseases (17.1%) and neoplastic diseases (14.3%). Infections were clinically recognized in 66.7% of cases and were missed or found to be incorrect in 33.3% of cases. Tuberculosis comprised 33.8% of the major bacterial infections and was clinically diagnosed in 82% of cases. Eighty nine percent of the major fungal infections were not suspected clinically. Rheumatic heart disease (43.8%) was the most common cardiovascular disorder and was clinically diagnosed in 93.3% of cases. Pulmonary vascular episodes were the least common cause of death and were not suspected clinically in 62.9% of cases. Malignancies were incorrectly diagnosed in 25.8% of cases. We conclude from this study that routine autopsies revealed major unexpected findings that are of clinical importance, and that a continued emphasis on autopsy evaluation is necessary for the improvement of the quality of patient care. PMID- 8432515 TI - Association of Sjogren's syndrome with pulmonary hypertension: report of two cases and review of the literature. AB - We report two autopsy cases of Sjogren's syndrome associated with pulmonary hypertension. The pulmonary muscular arteries of both cases showed concentric fibrocellular intimal proliferation, medial hypertrophy, and plexiform lesions. To determine the significance and pathogenesis of this rare association, we carried out morphometric and immunofluorescent studies and reviewed the seven similar cases reported in the literature. Depositions of immunoglobulin G, Clq, C3c, C4, and C5 were observed in the pulmonary arterial walls of both of our cases. Morphometric studies revealed increased medial thickness to radius ratios and intimal thickness to radius ratios of the pulmonary muscular arteries in both cases. Previously reported patients were all female, and those cases were frequently associated with Raynaud's phenomenon. This report provides additional and convincing evidence for an association of Sjogren's syndrome and plexogenic pulmonary hypertension based on a detailed study of two cases and a review of the literature. The significance and pathogenesis of this association were examined, but not clarified. However, our studies add to the accumulating data suggesting a link between autoimmune diseases and chronic pulmonary hypertension. PMID- 8432516 TI - The correlation of two argyrophilic nucleolar organizer region counting methods with bromodeoxyuridine-labeling index: a study of metastatic tumors of the brain. AB - Bromodeoxyuridine (BrdU) is a thymidine analog that is incorporated into cellular DNA in the synthetic phase. The BrdU-labeling index (BLI) thus reflects the S phase fraction. The argyrophilic nucleolar organizer regions (AgNORs) are silver stained granules that have been correlated with ploidy and/or S-phase fraction. Two AgNOR counting methods have been proposed to distinguish between ploidy and S phase fraction: the mean AgNOR (mAgNOR) count (the mean number of AgNOR granules in 100 cells), which is believed to reflect ploidy, and the AgNOR proliferative index (pAgNOR) (the percentage of cells exhibiting five or more AgNOR granules per nucleus), which is believed to reflect S-phase fraction. To evaluate the latter hypothesis we studied 19 tumors metastatic to the brain in patients who had received preoperative low-dose BrdU injections. Formalin-fixed, paraffin embedded sections of the resected tumors were stained using the indirect immunoperoxidase technique and a monoclonal antibody to BrdU. The BLI was determined by counting 1,000 tumor cells in each case; AgNOR silver staining was performed on sections of the same blocks studied for BLI. The correlation between pAgNOR counts and BLI was statistically significant (r = .649, P = .003). No statistically significant correlation could be obtained between mAgNOR counts and BLI (r = .421, P = .17). We conclude that the pAgNOR count can reliably reflect the proliferative activity of cells. The method can prove beneficial in situations in which cell kinetic analysis is needed and in which invasive procedures, such as BrdU injection, are not feasible or are contraindicated. PMID- 8432517 TI - The morphologic features of diversion colitis: studies of a pediatric population with no other disease of the intestinal mucosa. AB - Studies of diversion colitis have not shown a consistent pattern of histopathologic features, and many descriptions are difficult to interpret because of the presence of underlying intestinal mucosal disease. To define the histologic changes in patients free of other mucosal inflammatory disease, we studied the resected segments of bypassed colorectum from 37 patients with Hirschsprung's disease treated by a two-stage procedure, using rectal biopsy specimens taken for initial diagnosis and trimmings from proximal to the stoma as controls. Biopsy specimens from a further 14 patients of similar age but without colorectal mucosal disease were used as additional controls. The histology of the bypassed segment was abnormal in all patients. Twenty-six had diversion colitis characterized by diffuse follicular lymphoid hyperplasia; lamina propria expansion by plasma cells, lymphocytes, and some neutrophils; cryptitis; reactive epithelium; and mucin depletion. Crypt abscesses, aphthous ulcers, mild architectural distortion, and Paneth cell metaplasia were noted in more severe cases. The remaining 11 patients had mild follicular lymphoid hyperplasia and an increase in lymphoplasmacytic infiltrates, with absence of neutrophils, epithelial injury, and other changes seen in diversion colitis, a pattern we term "diversion reaction." Diversion colitis is common in children with a bypassed colorectum. It can be distinguished histologically from other mucosal diseases in most cases. We hypothesize that diversion reaction may be an inevitable consequence of colonocyte nutrient deficiency and that diversion colitis may be superimposed by a second insult, such as a low-grade pathogen. PMID- 8432518 TI - Comparison of microscopic vascularity in benign and malignant prostate tissue. AB - A variety of malignant neoplasms have been shown to induce capillary neovascularization, and in some cases the degree of vascularization appears to correlate with aggressive behavior and risk of metastasis. We hypothesized that carcinoma of the prostate also induces the formation of new capillaries, and we developed a method to quantify the relative density of microscopic vessels in carcinoma of the prostate compared with benign prostatic glandular tissue. The number of microvessel profiles in tissue sections was quantified by marking the vascular endothelial cells with antibodies to factor VIII-related antigen using standard immunohistochemistry techniques and comparing fields of adenocarcinoma with benign glandular tissue in 15 radical prostatectomy specimens. The analysis was facilitated by using the Optimas computerized image analysis system (Bioscan, Seattle, WA) with software written for this investigation. Fourteen of the 15 cases demonstrated significantly higher vascular density in the areas of carcinoma than in the benign tissues. Overall, the ratio of vessels per unit area in sections of carcinoma versus benign tissue was approximately double (ratio = 2.02; P < .001). In benign tissues the capillaries are restricted for the most part to the periglandular stroma immediately adjacent to the epithelium, whereas the distribution in carcinoma appears to be more random. The data demonstrate the increased density of capillaries in prostatic carcinoma when compared with benign prostate tissue. PMID- 8432519 TI - Lentoids within sacrococcygeal teratoma: origin by transdifferentiation? AB - Within a teratoma removed surgically from the sacrococcygeal region of a female newborn, clusters of lens-like cells (lentoids) surrounded by the immature tissue of the neural retina were revealed by routine histologic analysis. Comparison of the cytologic and microtopographic characteristics of lentoids that develop in experimental embryo-derived teratomas suggests that the lentoids within the sacrococcygeal teratoma originate by transdifferentiation (cell-type conversion, metaplasia) of cells of the immature neural retina or the pigmented retinal epithelium. The embryonic origin of sacrococcygeal teratomas is discussed in the context of complex morphogenetic features at the posterior end of the early embryo. PMID- 8432520 TI - Genomics: stock-taking after 5 years. PMID- 8432521 TI - Fine mapping and narrowing of the genetic interval of the spinal muscular atrophy region by linkage studies. AB - The gene for autosomal recessive proximal spinal muscular atrophy (SMA) has recently been mapped to chromosome 5q12.2-q13, within a genetic distance of about 6 cM, and is proximally flanked by the locus D5S6 and distally by D5S112. Here, we report linkage analyses in 64 SMA families with nine polymorphic markers closely linked to the SMA gene, which allowed us to narrow the SMA region to about 4 cM and to define a new proximal genetic border by the locus D5S125 (EF(TG/AG)n. Based on haplotype analysis and specific recombination events, the following order of the loci was determined: 5cen-D5S76-D5S6-D5S125-SMA-(5'MAP-1B 3'MAP- 1B)/D5S112-JK53CA1/2-(D5S39-D5S127)-5qter. The location of the SMA gene between D5S125 and MAP-1B is further supported by multipoint linkage analysis. PMID- 8432522 TI - Abnormal segregation of alleles in CEPH pedigree DNAs arising from allele loss in lymphoblastoid DNA. AB - Somatic events that result in the reduction to hemi- or homozygosity at all loci affected by the event have been identified in lymphoblastoid DNA from mothers of two CEPH families. Using suitably informative probes, the allele deficiencies were detected by the abnormal transmission of alleles from grandparents to grandchildren, with the apparent absence of the alleles from the parent. Undetected somatic deficiencies in family DNAs could result in misscoring of recombination events and consequently introduce errors into linkage analysis. PMID- 8432523 TI - The topographic organization of repetitive DNA in the human nucleolus. AB - The nucleolus is a highly specialized nuclear domain where ribosomal DNA (rDNA) is transcribed and preribosomes are assembled. We investigated the molecular organization of the human lymphocyte nucleolus by fluorescence in situ hybridization and confocal laser scanning microscopy and found that transcribed rDNA and nontranscribed ribosomal intergenic spacer (IGS) sequences colocalized to discrete regions frequently on the nucleolar periphery of phytohemagglutinin stimulated cells. The 5S rDNA gene cluster located on the long arm of chromosome 1 was not regularly associated with the nucleolus. Short interspersed (SINE) Alu elements detected by BLUR 11 were distributed diffusely throughout the nucleus but were severely underrepresented in the nucleolus, whereas an Alu element subcloned from the IGS detected sequences enriched in the nucleolus but sparsely represented in the remainder of the nucleus. In contrast, long interspersed (LINE) Kpn elements, which were located at the nucleolus, were not found in rDNA but were identified outside the ribosomal gene complex on the short arm of at least one acrocentric chromosome. A human chromosome 21-derived alphoid sequence that hybridized to the centromere was localized outside but near the nucleolus, and nonribosomal DNA consisting of a tandemly repeated simple sequence cluster derived from the short arm of chromosome 15 was organized in a compact fashion in the nucleolus. Our study provides new insight into the content and structure of the human nucleolus and illustrates that the unique organization of repetitive DNA on the acrocentric chromosome short arms is reflected in the topographic organization of the nucleolus. PMID- 8432524 TI - Characterization and chromosomal assignment of a human cDNA encoding a protein related to the murine 102-kDa cadherin-associated protein (alpha-catenin). AB - We report the characterization of a human cDNA encompassing the complete coding region of a 945-residue putative protein (CAP-R) 80% identical to the recently described murine 102-kDa alpha-catenin (CAP102). The CAP-R protein mostly differs from CAP102 by the presence of a 48-residue insert. This insert exhibits similarity with a segment of the type 1 neurofibromatosis gene product. The analysis of a publicly available human "expressed sequence tag" collection revealed the existence of another human cDNA more closely related (89% identical) to CAP102. This strongly suggests that CAP-R is not the human homologue of the murine 102-kDa alpha-catenin but a new closely related gene of the vinculin family. This is further supported by the computed mutation rates falling outside the range observed for mammalian orthologous genes. Using in situ hybridization, the CAP-R gene could be mapped to the p11.1-p12 region of human chromosome 2 and to the homologous B3-D region of mouse chromosome 6. PMID- 8432525 TI - Fluorescence in situ hybridization mapping of human chromosome 19: cytogenetic band location of 540 cosmids and 70 genes or DNA markers. AB - We report here the band location of 540 cosmids mapped to chromosome 19. The cosmids were mapped by fluorescence in situ hybridization (FISH) relative to chromosomal bands produced by DAPI/actinomycin staining. The cosmids are distributed throughout the chromosome, with a sampling bias for the q-arm. A detailed analysis of the distribution of three different subtelomeric and 22 pericentromeric chromosome 19 cosmids on other chromosomes is also reported. Colony hybridization identified 142 cosmids that contain sequences representing genes or DNA markers that map to chromosome 19. FISH mapping of these cosmids sublocalizes a total of 70 genes and DNA markers on chromosome 19, revises the previously published map assignments of 2 genes, and narrows the location of over 20 markers. PMID- 8432526 TI - The human decorin gene: intron-exon organization, discovery of two alternatively spliced exons in the 5' untranslated region, and mapping of the gene to chromosome 12q23. AB - Decorin is a chondroitin/dermatan sulfate proteoglycan expressed by most vascular and avascular connective tissues and, because of its ability to interact with collagen and growth factors, has been implicated in the control of matrix assembly and cellular growth. To understand the molecular mechanisms involved in regulating its tissue expression, we have isolated a number of genomic clones encoding the complete decorin gene. The human decorin gene spans over 38 kb of continuous DNA sequence and contains eight exons and very large introns, two of which are 5.4 and > 13.2 kb. We have discovered two alternatively spliced leader exons, exons Ia and Ib, in the 5' untranslated region. These exons were identified by cloning and sequencing cDNAs obtained by polymerase chain reaction amplification of a fibroblast cDNA library. Using Northern blotting or reverse transcriptase PCR, we detected the two leader exons in a variety of mRNAs isolated from human cell lines and tissues. Interestingly, sequences highly (74 87%) homologous to exons Ia and Ib are found in the 5' untranslated region of avian and bovine decorin, respectively. This high degree of conservation among species suggests regulatory functions for these leader exons. In the 3' untranslated region there are several polyadenylation sites, and at least two of these sites could give rise to the transcripts of approximately 1.6 and approximately 1.9 kb, typically detected in a variety of tissues and cells. Using a genomic clone as the labeled probe and in situ hybridization of human metaphase chromosomes, we have mapped the decorin gene to the discrete region of human chromosome 12q23. This study provides the molecular basis for discerning the transcriptional control of the decorin gene and offers the opportunity to investigate genetic disorders linked to this important human gene. PMID- 8432527 TI - Human decorin gene: intron-exon junctions and chromosomal localization. AB - All of the protein-encoding exons and the 3' flanking region of the human decorin gene have been cloned and partially sequenced. The locations of the intron-exon junctions within the coding portion of the gene were identical to those found for the homologous human gene, biglycan. The sizes of the introns in the decorin gene, however, were substantially larger than those of the same introns of the biglycan gene. Portions of introns 1, 2, and 3 as well as exon 1 were not found during our extensive screening process. The 5' end of intron 2 was found to have an AG-rich region followed immediately by a CT-rich region. Furthermore, the 5' end of intron 3 was very rich in thymidine, whereas the 3' end of intron 7 was rich in adenosine. Several cDNA clones constructed from cultured human bone cell mRNA were found to contain a different sequence at the 5' end compared to that previously published for mRNA from a human embryonic fibroblast cell line. We were also unable to find the alternate 3' flanking region of the previously published cDNA sequence. We have mapped the human decorin gene by in situ methods to chromosome 12q21.3. PMID- 8432528 TI - Human carbonyl reductase (CBR) localized to band 21q22.1 by high-resolution fluorescence in situ hybridization displays gene dosage effects in trisomy 21 cells. AB - Human carbonyl reductase (CBR) belongs to a group of NADPH-dependent enzymes called aldo-keto reductases. The enzyme can function as an aldo-keto reductase or as a quinone reductase with potential for modulating quinone-mediated oxygen free radicals. The CBR gene was mapped by high-resolution fluorescence in situ hybridization to band 21q22.12, very close to the SOD1 locus at position 21q22.11. CBR displayed gene dosage effects in trisomy 21 human lymphoblasts at the DNA and mRNA levels. Lymphoblasts with increasing chromosome 21 ploidy also showed increased aldo-keto reductase activity and increased quinone reductase activity. Both aldo-keto reductase activity and quinone reductase activity have been shown to be associated with carbonyl reductase. The location of CBR near SOD1 and the increased enzyme activity and potential for free radical modulation in trisomy 21 cells implicate CBR as a candidate for contributing to the pathology of certain diseases such as Down syndrome and Alzheimer disease. PMID- 8432529 TI - The human interleukin-1 receptor antagonist (IL1RN) gene is located in the chromosome 2q14 region. AB - The gene for human interleukin-1 receptor antagonist (IL1RN) has been assigned to chromosome 2 on the basis of Southern blot analysis of a series of human-Chinese hamster cell hybrids. Using a yeast artificial chromosome containing the IL1RN gene as a probe, the human IL1RN gene was localized to the long arm of chromosome 2 at band 2q14.2 by fluorescence in situ hybridization. This site is near the positions of genes for human IL-1 alpha, IL-1 beta, and types I and II IL-1 receptors, as reported by other laboratories. PMID- 8432530 TI - Molecular and cytogenetic characterization of a Chinese hamster/human hybrid cell line containing a der (21)t(Ypter-->cenY::cen21-->21qter) chromosome. AB - Human/rodent somatic cell hybrids have been exceedingly useful in assigning human genes and DNA sequences to specific human chromosomes. As new technologies for analyzing the human chromosome complement of such human/rodent hybrid cells become available, it is of critical importance that these be applied to enhance characterization of existing hybrids. This is particularly important since human chromosomes in such hybrids have been observed to rearrange with time. We report here the use of fluorescence in situ hybridization of DNA probes to metaphase chromosomes to analyze one hybrid designated 72532X6. This analysis shows that the chromosome suspected to be a normal human chromosome 21 in this hybrid is actually a translocation chromosome containing Yp and 21q. In addition, the hybrid contains a fragment of human chromosome 9 translocated to a Chinese hamster chromosome. Analysis of the chromosomes from the human donor indicates that his chromosomes are normal. Thus, this translocation chromosome appears to have arisen after formation of the hybrid. PMID- 8432531 TI - Chromosomal localization of mouse bullous pemphigoid antigens. BPAG1 and BPAG2: identification of a new region of homology between mouse and human chromosomes. AB - Two bullous pemphigoid antigens, BPAG1 and BPAG2, have been recently cloned and mapped to human chromosomes 6p12-p11 and 10q24.3, respectively. In this study, we localized the corresponding mouse genes by interspecific backcross analysis. Bpag 1 mapped to the proximal region of mouse chromosome 1, identifying a new region of homology between human chromosome 6 and mouse chromosome 1. Bpag-2 mapped to the distal end of mouse chromosome 19 in a region of homology to human chromosome 10q. These assignments confirm and extend the relationships between the human and the mouse chromosomes. PMID- 8432532 TI - The genes for the lipopolysaccharide binding protein (LBP) and the bactericidal permeability increasing protein (BPI) are encoded in the same region of human chromosome 20. AB - The lipopolysaccharide binding protein is an acute-phase reactant produced during gram-negative bacterial infections. The bactericidal/permeability increasing protein is associated with human neutrophil granules and has bactericidal activity on gram-negative organisms. In addition to their functional relationship, both proteins share extensive structural similarity. This article demonstrates that the genes for both proteins are in the same region of human chromosome 20, between q11.23 and q12. PMID- 8432533 TI - Mapping of a liver phosphorylase kinase alpha-subunit gene on the mouse X chromosome. AB - Phosphorylase kinase (PHK) is a regulatory enzyme of the glycogenolytic pathway composed of a complex of four subunits. We recently mapped the muscle alpha subunit gene (Phka) to the mouse X chromosome in a region syntenic with the proximal long arm of the human X chromosome and containing the human homologue of this gene, PHKA. We now report the mapping of the liver alpha-subunit gene to the telomeric end of the mouse X chromosome. This mapping position would suggest a location for the human liver alpha-subunit gene on the proximal short arm of the X chromosome, a region recently implicated in X-linked liver glycogenosis (XLG). PMID- 8432534 TI - Localization of human cell cycle regulatory genes CDC25C to 5q31 and WEE1 to 11p15.3-11p15.1 by fluorescence in situ hybridization. AB - The cell cycle control genes are highly conserved during evolution since they play a key role in the regulation of cell division. We have localized CDC25C and WEE1 respectively at 5q31 and 11p15.3-11p15.1 using fluorescent in situ hybridization of cDNA probes on human chromosomes. This shows that genes acting through a regulatory phosphorylation cascade are not clustered on the same chromosome. Furthermore, they appear to map on chromosomal regions involved in tumorigenesis. The 5q23-q31 region of chromosome 5 is deleted in some hematologic disorders, and the p15 region of chromosome 11 is involved in development of embryonic tumors. PMID- 8432535 TI - Localization of the murine activating transcription factor 4 gene to mouse chromosome 15. AB - Restriction fragment length variant analysis employing a mouse cDNA probe was used to localize the gene encoding murine activating transcription factor 4 (ATF 4) to mouse chromosome 15 in close proximity to Sis (the cellular homolog of the simian sarcoma virus oncoprotein). Previous studies suggest that conserved linkage relationships exist between this region of mouse chromosome 15 and human chromosome 22q. The chromosomal locations of genes encoding most members of the ATF and cyclic AMP response element binding protein (CREB) subfamily of b-zip proteins have not been determined. This study demonstrates that the location of the gene for murine ATF-4 is not linked to the genes for JUN family members, CREB1 and CREB2. Further mapping of individual ATF/CREB subfamily members in the mouse will provide insight into the evolution of this multigene family. PMID- 8432536 TI - The pituitary hormones arginine vasopressin-neurophysin II and oxytocin neurophysin I show close linkage with interleukin-1 on mouse chromosome 2. AB - Arginine vasopressin (AVP) and oxytocin (OXT) are posterior pituitary hormones. AVP is involved in fluid homeostasis, while OXT is involved in lactation and parturition. AVP is derived from a larger precursor, pre-pro-arginine-vasopressin neurophysin II (prepro-AVP-NP II; AVP), and is physically linked to prepro oxytocin-neurophysin I (prepro-OXT-NP I; OXT). The genes for AVP and OXT are separated by only 12 kb of DNA in humans, whereas in the mouse 3.5 kb of intergenic sequence lies between Avp and Oxt. Interspecific backcross analysis has now been used to map the Avp/Oxt complex to chromosome 2 in the mouse. This map position confirms and extends the known region of linkage conservation between mouse chromosome 2 and human chromosome 20. PMID- 8432537 TI - Identification of six new Gaucher disease mutations. AB - The four most common mutations account for 97% of the Gaucher disease-producing alleles in Jewish patients and 75% of the alleles in non-Jewish patients. Although at least 15 other mutations and some examples of gene conversion and/or fusion genes have been described, a number of mutations remain unidentified. We have now identified six new mutations, a deletion of a C at the 72 position of the cDNA, a 481C-->T mutation (122Pro-->Ser), a 751T-->C (212Tyr-->His), a 1549G- >A (478Gly-->Ser), a 1604G-->A (496Arg-->His), and a 55-bp deletion. All but one of these were found in single families. The 1604A mutation, however, was observed in four unrelated individuals. PMID- 8432538 TI - Localization of the human poly(A)-binding protein gene (PAB1) to chromosomal regions 3q22-q25, 12q13-q14, and 13q12-q13 by in situ hybridization. AB - A cDNA clone encoding the human polyadenylate-binding protein (PABP) was isolated and mapped to the genome by in situ hybridization. The cDNA was found to bind preferentially to chromosomal regions 3q22-q25, 12q13-q14, and 13q12-q13. In addition, Southern blot analysis of genomic DNA using a PABP cDNA probe revealed a complex pattern of bands. The results indicate that PABP belongs to a multigene family of related sequences. PMID- 8432539 TI - Evidence for further genetic heterogeneity in autosomal dominant retinitis pigmentosa. AB - We have investigated the possible involvement of further genetic heterogeneity in autosomal dominant retinitis pigmentosa using a previously unreported large Irish family with the disease. We have utilized polymorphic microsatellite markers to exclude the disease gene segregating in this family from 3q, 6p, and the pericentric region of 8, that is, each of the three chromosomal regions to which adRP loci are known to map. Hence, we provide definitive evidence for the involvement of a fourth locus in autosomal dominant retinitis pigmentosa. PMID- 8432540 TI - Mapping on human and mouse chromosomes of the gene for the beta-galactoside binding protein, an autocrine-negative growth factor. AB - The structural gene for beta-galactoside-binding protein (Lgals-1), a cell growth regulatory molecule and cystostatic factor, is assigned to the E-region of mouse chromosome 15 and to the region q12-q13.1 of human chromosome 22. The evolutionary conservation of these two regions has been previously suggested from comparative mapping of several loci. These include the murine SIS oncogene (Pdgfb) and its human homolog, the platelet-derived growth factor-beta polypeptide, PDGFB. The findings presented here extend the genetic homology of the two regions. PMID- 8432541 TI - Human PCK1 encoding phosphoenolpyruvate carboxykinase is located on chromosome 20q13.2. AB - Cytoplasmic liver phosphoenolpyruvate carboxykinase (GTP) (PEPCK) catalyzes a rate-limiting step in gluconeogenesis. Primers derived from the rat liver PEPCK sequence were used to amplify a portion of the human liver cDNA and to screen a YAC library of human genomic DNA. The sequences of human and rat PEPCK cDNA differed at 16% of the nucleotides compared (45/291). Analysis of a human/rodent hybrid mapping panel demonstrated concordant segregation of PCK1 with chromosome 20. Fluorescence in situ hybridization with YAC DNA further localized PCK1 to subband 20q13.2. PMID- 8432542 TI - The chromosomal localization of the human follicle-stimulating hormone receptor gene (FSHR) on 2p21-p16 is similar to that of the luteinizing hormone receptor gene. AB - Two cDNA probes (5' and 3' region) corresponding to the human follicle stimulating hormone receptor gene (FSHR) were used for chromosomal localization by in situ hybridization. The localization obtained on chromosome 2p21-p16 is similar to that of the luteinizing hormone/choriogonadotropin (LH/CG) receptor gene. PMID- 8432543 TI - Genetic and physical map of 11 short tandem repeat polymorphisms on human chromosome 6. AB - A linkage map of 11 short tandem repeat polymorphisms was constructed for human chromosome 6. The order from p to qter was F13A1-D6S105-D6S254-D6S251-D6S252 D6S24 9-(ARG1-D6S87)-D6S250-D6S255-D6S253. For the region spanned by the 6q markers, the male map distance was less than half the female map distance (58 and 126.3 cM, respectively). Two-point linkage analysis was also used to position the markers relative to markers in the CEPH public database. Physical mapping of these markers was completed using a somatic cell hybrid panel that contained varying segments of chromosome 6. Two of the markers mapped to the short arm of chromosome 6; the remainder were spaced over 86.5 cM of the long arm from 6q13 to 6qter. The linkage and physical maps were completely consistent. PMID- 8432544 TI - Cloning and characterization of EagI YACs from human chromosome 21. AB - Yeast artificial chromosomes (YACs) were made from a total EagI digest of DNA from a mouse-human chromosome 21 hybrid cell line. Approximately 3750 YACs, corresponding to 75-125 human YACs, with an average size of approximately 100 kb were recovered. Southern hybridization indicates that the chimera frequency in this library may be less than 3%. Thirty-four of the human EagI YACs were regionally assigned by a number of methods. Some YACs were regionally assigned to one of six chromosome regions by hybridization of Alu-PCR products from the YAC against Alu-PCR-amplified DNA from a panel of hybrid cell lines that contain various parts of chromosome 21. Additional YACs were regionally assigned by fluorescence in situ hybridization using either biotinylated Alu-PCR products or yeast genomic DNA from the YAC-containing strains as probes. The regionally assigned EagI YACs are located preferentially in two regions of the chromosome: near the q telomere and in the p-arm ribosomal gene region. PMID- 8432545 TI - The amyloid precursor-like protein (APLP) gene maps to the long arm of human chromosome 19. PMID- 8432546 TI - The IPP gene is assigned to human chromosome 1p32-1p22. PMID- 8432547 TI - Sublocalization of seven human simple sequence repeat polymorphic markers: D5S349, D5S351, and D5S355 to 5q11.2-q13.1, D5S350 to 5p13.1-p14, D5S352 to 5q31.2-q33.1, D5S353 to 5q33.2-qter, and D5S354 to 5q13.2-q15. PMID- 8432548 TI - Localization of a potassium channel gene (KCNE1) to 21q22.1-q22.2 by in situ hybridization and somatic cell hybridization. PMID- 8432549 TI - In situ localization of the genetic locus encoding the lysosomal acid lipase/cholesteryl esterase (LIPA) deficient in Wolman disease to chromosome 10q23.2-q23.3. PMID- 8432550 TI - An extended genetic linkage map and an "index" map for human chromosome 17. AB - Our previous genetic map for chromosome 17 has been expanded to include 72 loci defined by 90 RFLP markers and four microsatellite markers assayed by the polymerase chain reaction. Forty-one of these loci were ordered with odds greater than 1000:1 against local inversion, and the other 31 were ordered within 95% confidence limits. From the set of 41 unambiguously mapped loci, 14 well-spaced "index markers" can be extracted for efficient genetic studies. The complete map spans 173 cM (136 cM in males and 214 cM in females); average spacing between markers is 4.2 cM. PMID- 8432551 TI - Twelve new polymorphic microsatellites on human chromosome 22. AB - A strategy directed at constructing polymorphic STSs from human chromosome 22 has yielded 15 poly(TG) microsatellite markers. A short insert plasmid library containing flow-sorted chromosome 22 DNA was screened with a labeled poly(AC) probe. A combination of sequencing techniques was used to identify the poly(TG) targets, primers were designed to flank these targets, and PCR screening was carried out on a panel of genomic and hybrid DNAs to determine heterozygosity and regional localization on chromosome 22. Twelve of the STSs are polymorphic. Markers with high heterozygosity have been localized to three subregions of 22q, with seven in the Giemsa-dark 22q12 band. The new chromosome 22 loci will be useful for mapping disease loci, for linkage analysis, and for PCR-based contig construction in the ongoing effort to map human chromosome 22. PMID- 8432552 TI - The structure of the human intron-containing S8 ribosomal protein gene and determination of its chromosomal location at 1p32-p34.1. AB - The intron-containing gene encoding human ribosomal protein S8 (RPS8) has been cloned and characterized, and its chromosomal position determined. Using a PCR based cloning strategy, we have isolated the intron-containing gene in the presence of its many processed pseudogenes and determined the DNA sequence of the entire gene and its upstream and downstream flanking regions. The human RPS8 gene is 3161 bp in length and comprises six exons. Despite lacking a consensus TATA box, primer extension analysis indicates that the start of transcription is precisely located at a C residue within an 11-bp oligopyrimidine tract. The first exon, which contains the ATG start codon, is just 27 bp in length. The DNA sequence 5' to the RPS8 gene and within the first exon and intron shows several features of a CpG island. A combination of Southern blotting, PCR, and fluorescence in situ hybridization analyses has enabled the chromosomal location of the human RPS8 gene to be determined as 1p32-p34.1. PMID- 8432553 TI - A microsatellite genetic linkage map of human chromosome 13. AB - We have characterized 21 polymorphic (CA)n microsatellites for the development of a genetic map of chromosome 13. Fifteen markers were isolated from a flow-sorted chromosome 13 library, four CA repeats were derived from NotI-containing cosmid clones, and two polymorphic markers were described previously (J. L. Weber, A. E. Kwitek, and P. E. May, 1990, Nucleic Acids Res. 18: 4638; L. Warnich, I. Groenwald, L. Laubscher, and A. E. Retief, 1991, Am. J. Hum. Genet. 49(Suppl.): 372 (Abstract)). Regional localization for all of the markers was performed by amplification of DNA from five somatic cell hybrids containing different deletions of chromosome 13. Genetic markers were shown to be distributed throughout 6 of the 11 resolvable chromosomal subregions. Using data from nine families provided by the Centre d'Etude du Polymorphisme Humain (CEPH), a framework map of 12 of these 21 markers was developed. Six of the 12 markers form three pairs, with each two members of a pair being tightly linked, such that nine systems of markers can be distinguished. The average heterozygosity of these 12 markers is 0.75. The total length of the sex-averaged map is 65.4 cM (Kosambi), with an average distance of 8.2 cM between systems of markers (eight intervals). Seven remaining markers were placed provisionally into the framework map. PMID- 8432554 TI - Linkage studies of the esterase D and retinoblastoma genes to canine copper toxicosis: a model for Wilson disease. AB - Canine copper toxicosis, an autosomal recessive disorder, is prevalent among certain dog breeds. It results in liver disease from copper accumulation and toxicity similar to the human autosomal recessive disorder, Wilson disease. The Wilson disease locus has been mapped to 13q and is closely linked to the esterase D and retinoblastoma genes. We developed informative polymorphic systems in the dog using the human cDNA clones of the esterase D and retinoblastoma loci as probes. We investigated the linkage relationship of these two loci to the copper toxicosis locus, and to each other in the dog. Our results indicate that none of the loci are closely linked in the dog. Linkage of copper toxicosis to the retinoblastoma locus can be excluded up to 13% recombination, and to esterase D up to 5% recombination. Furthermore, esterase D and retinoblastoma, tightly linked in the mouse and human genomes, are not found to be closely linked in the canine genome. PMID- 8432555 TI - Evidence for locus heterogeneity in autosomal dominant torsion dystonia. AB - Idiopathic torsion dystonia (ITD) is most commonly an autosomal dominant disorder with reduced penetrance and variable expression. A locus on the distal long arm of chromosome 9 has been identified in one large non-Jewish and several Jewish families in the United States. Linkage analysis in a large Australian kindred with ITD, also containing two patients with Wilson's disease, excludes a locus for ITD in chromosome 9q34 or the region of chromosome 13 containing the Wilson disease gene. This study provides evidence for locus heterogeneity in autosomal dominant ITD and also gives additional information on gene order in chromosome 9q. PMID- 8432556 TI - DNA polymorphisms in the 3' untranslated region of genes on human chromosome 21. AB - DNA polymorphisms can be used to place loci and phenotypes on the linkage maps of human chromosomes. In an effort to localize genes on the linkage map of human chromosome 21 better, we examined their 3' untranslated (3'UT) regions for the presence of polymorphisms. We amplified the 3'UT region of 17 genes of chromosome 21 by the polymerase chain reaction and subjected the product to single-stranded conformation analysis (SSCA). We have found eight polymorphisms in the 3'UT region of genes. The total area examined was 8144 nucleotides and therefore the variability detected by this method was 1 in 1018 nucleotides. This is not different from the estimated variability of DNA sequences based on restriction analysis. Sequence analysis revealed that all polymorphisms found are due to single nucleotide substitutions. Additional polymorphisms were identified in the last intron of BCEI gene and in the 3'-flanking region of the S100B gene. We conclude that the 3'UT region of genes is a relatively rich source of polymorphisms and that SSCA is an effective method of detecting the normal sequence variation in the human genome. PMID- 8432557 TI - Pregnenolone metabolism in rodent embryonic neurons and astrocytes. AB - The rat CNS has been previously shown to synthesize pregnenolone (PREG) and to convert it into progesterone (PROG) and some of its 5 alpha-reduced metabolites. However, the brain cell types involved in the metabolic conversions of PREG are poorly known. Selective conditions were used to obtain purified cultures of neurons and astrocytes from mouse or rat fetal striatum and cerebral cortex. Neurons converted PREG to only one identified metabolite, 20 alpha-dihydro PREG, whereas astrocytes converted PREG also to PROG, 5 alpha-dihydro PROG, and 3 alpha (3 beta)-5 alpha-tetrahydro PROG. Therefore, astrocytes can convert the neurosteroid PREG into the steroid hormone PROG and the neuromodulatory steroid 3 alpha, 5 alpha-tetrahydro PROG, whereas neurons lack the delta 5-3 beta hydroxysteroid dehydrogenase isomerase activity (and cholesterol side-chain cleavage activity), necessary for the biosynthesis of PROG. Provision of steroid substrates is another example of cross-talk between glial cells and neurons. PMID- 8432558 TI - Stimulation of astrocyte proliferation by purine and pyrimidine nucleotides and nucleosides. AB - Proliferation of brain astrocytes as a result of cell death has been well documented in vivo. Dying cells release purine and pyrimidine nucleosides and nucleotides and their deoxy derivatives both from soluble intracellular pools and from DNA and RNA. Previously, we have observed that purine nucleosides and nucleotides stimulate chick astrocyte proliferation in vitro. To further our analysis, we questioned whether pyrimidines or the deoxy derivatives of purine nucleosides and nucleotides might also be astrocyte mitogens. Pyrimidine nucleosides, nucleotides, and their deoxynucleotide derivatives were uniformly inactive. In contrast, deoxyguanosine, deoxyadenosine, and their mono-, di-, and triphosphates stimulated thymidine incorporation into astrocytes at concentrations similar to those at which their ribonucleoside and ribonucleotide analogues were active. Inosine, IMP, ITP, and hypoxanthine were active, whereas xanthine and xanthosine were not. However, XMP, XDP, and XTP stimulated thymidine incorporation. The effects of the nucleosides and deoxynucleosides were inhibited by antagonists of adenosine A2 receptors. These data indicate that most purine nucleosides, deoxynucleosides, and their 5' mono, di-, and triphosphate derivatives released from damaged cells are capable of stimulating astrocyte proliferation in vitro and may contribute to astrocyte proliferation in vivo following injury to the CNS. PMID- 8432559 TI - Detection of lysosomal cysteine proteinases in microglia: flow cytometric measurement and histochemical localization of cathepsin B and L. AB - The activation and differentiation of microglia is a prominent pathophysiological process in numerous inflammatory and demyelinating diseases of the central nervous system, including Alzheimer's disease and the AIDS encephalopathy. The tissue damage during these diseases has partly been attributed to lipid peroxidating reactive oxygen intermediates for which activated microglia are a major source. The destruction of tissue may also involve the release of proteolytic enzymes, such as the lysosomal cysteine proteinases cathepsin B and L, which are present notably in phagocytic cells. The cathepsins B and L are endopeptidases with a substrate specificity including important proteins, like myelin basic protein, extracellular matrix components, or the class II major histocompatibility complex. Because of this pathophysiological relevance the cathepsins B and L were chosen for histochemical demonstration in isolated and cultured rat microglia and measurement by a new flow cytometric method. Cathepsin B/L activity was measured flow cytometrically in single viable cells by the intracellular cleavage of non-fluorescent (Z-Phe-Arg)2-rhodamine 110 to the green fluorescent monoamide Z-Phe-Arg-rhodamine 110 and rhodamine 110. In microglia we measured a cathepsin B/L activity that was 2.5 times higher than in thioglycolate elicited, i.e., inflammatory peritoneal rat macrophages. In elicited peritoneal macrophages the formation of fluorescent product was 6.2 times higher than in unstimulated resident peritoneal macrophages, demonstrating that the activation and differentiation of mononuclear phagocytes is accompanied by an increased cathepsin B/L enzyme activity. The subcellular localization of cathepsin B/L activity in plated viable microglia was demonstrated histochemically by the use of Z-Ala-Arg-Arg-4-methoxy-2-naphthylamide. Its blue fluorescent cleavage product 4-methoxy-2-naphthylamide was found in lysosomes. Our study shows that activated microglia are an important potential source of cathepsin B/L. This is particularly interesting as enzymatically active cathepsins have recently been found extracellularly at high levels in the senile plaques of Alzheimer's disease, which are known to contain many activated microglia. The release of proteinases by microglia may play a crucial role in the pathomechanism of tissue destructing diseases in the brain. PMID- 8432560 TI - Pleural macrophages differentially alter mesothelial cell growth and collagen production. AB - Intrapleural tetracycline (TCN) results in pleural macrophage influx and pleural fibrosis; intrapleural carrageenan (CAR) induces macrophage influx without fibrosis. Because macrophage products can modulate mesothelial cell activity, we investigated the role of TCN- and CAR-induced pleural macrophages on mesothelial cell growth can collagen production. Rabbit pleural macrophages, isolated by plastic adherence 72 h after 20 mg/kg TCN or 10 mg CAR instilled intrapleurally, were cultured for 20 h. Macrophage-conditioned media (MCM) from TCN-or CAR-induce pleural macrophages (TCN MCM, CAR MCM, respectively), were added to non-confluent or confluent rat visceral pleural mesothelial cells and compared to the effects of TCN and CAR. Nonconfluent mesothelial cells were harvested 72 h later for hemacytometry cell counts. A 20-h pulse of [3H] proline (1 mu Ci, 30 Ci/mM) preceded 72-h-cell harvesting of confluent cells. Collagen content was determined in the cell fraction and cell media separately after bacterial collagenase exposure. Mesothelial cells exposed to TCN MCM were found to have decreased numbers when compared to all groups (P < 0.05) except CAR. Cell media collagen content was increased in all macrophage-conditioned-media and chemical-exposed groups compared with control, with TCN MCM having a larger increase than TCN alone (P < 0.05). We conclude that stimulated pleural macrophages release a factor(s) that alters mesothelial cell growth and collagen production and that TCN- and CAR-stimulated pleural macrophages are functionally different. These in vitro mesothelial cell alterations may be important in the genesis of TCN pleurodesis. PMID- 8432561 TI - Alpha 1-acid glycoprotein expression in human leukocytes: possible correlation between alpha 1-acid glycoprotein and inflammatory cytokines in rheumatoid arthritis. AB - alpha 1-Acid glycoprotein is an acute-phase reactant that becomes markedly elevated in serum during inflammation and has an immunosuppressive effect on lymphocyte functions. Patients with collagen diseases had significant increases of alpha 1-acid glycoprotein in their serum and on the surface of peripheral leukocytes compared with controls. The levels from patients with rheumatoid arthritis were higher than those from patients with systemic lupus erythematosus, mixed connective tissue disease, and Behcet's disease. In patients with rheumatoid arthritis, the value of serum alpha 1-acid glycoprotein correlated with disease activity. Among leukocyte subpopulations, monocytes showed more alpha 1-acid glycoprotein on their surface than polymorphonuclear leukocytes and lymphocytes. The cell surface expression of alpha 1-acid glycoprotein on cultured monocytes surface peaked after 48 h. Interleukin-1 beta and tumor necrosis factor alpha stimulated the production of alpha 1-acid glycoprotein RNA message in peripheral blood mononuclear cells over 18-24 h during cell culture. The results show that serum alpha 1-acid glycoprotein reflects systemic disease activity in rheumatoid arthritis. Furthermore, monocytes may serve as a source of production of alpha 1-acid glycoprotein. PMID- 8432562 TI - Differential binding of bacterial lipopolysaccharide to bovine peripheral-blood leukocytes. AB - The response of mammalian monocytes and macrophages to bacterial lipopolysaccharide (LPS) may be influenced by serum factors that increase or decrease the propensity of LPS to bind to cell surfaces. We used fluorescence flow cytometric analysis to investigate the capability of bovine peripheral-blood leukocytes to bind LPS in the presence or absence of bovine serum. At all concentrations of FITC-LPS tested (LPS from E. coli 0111:B4; 10 ng/ml, 100 ng/ml, 1 micrograms/ml), monocytes, lymphocytes, and granulocytes bound more FITC-LPS in the presence of 10% bovine serum than in serum-free conditions (P < 0.01). At the intermediate concentration tested (100 ng/ml), monocytes displayed a relative fluorescence intensity (RFI) of 2.27 +/- 1.24 units without serum and 17.48 +/- 8.05 with 10% serum. Values for granulocytes were similar to those of monocytes, 3.55 +/- 1.31 without and 19.24 +/- 6.93 with serum, and values for lymphocytes were 1.89 +/- 0.47 RFI units without serum and 6.27 +/- 2.61 RFI units with serum. At 10 ng/ml and 1 microgram/ml FITC-LPS the RFI of monocytes and granulocytes were also similar and not significantly different, and both bound significantly more LPS than lymphocytes (P < 0.01). When 100 ng/ml FITC-LPS was coincubated with leukocytes, 10% serum, and a 100-fold excess of unlabeled LPS, the amount of FITC-LPS bound to monocytes was reduced from 23.99 to 7.23 RFI units (P < 0.01), reduced from 22.00 to 7.30 RFI units with granulocytes (P < 0.05), and reduced from 7.51 to 2.29 RFI units (P < 0.10) with lymphocytes. These data demonstrate that factors in bovine serum significantly amplify the association of LPS with peripheral-blood leukocytes and that increased binding of LPS is greatest with monocytes and granulocytes. PMID- 8432563 TI - Direct and indirect effects of E. coli lipopolysaccharide on isolated human polymorphonuclear granulocytes and mixed leukocytes. AB - Polymorphonuclear neutrophil granulocytes (PMN) may contribute to the lung injury induced by nonpulmonary infections with gram-negative bacteria. The direct effect of E. coli lipopolysaccharide (LPS) on isolated human PMN or mixed leukocytes (ML), as well as the priming effect of preincubating cells with LPS, was examined in assays measuring the maximal rate of oxygen consumption (OC), cell chemiluminescence (CHML), and aggregation (AGG). LPS, 1-10 micrograms/ml, caused no acute response in PMN or ML suspended in Fisher's-HEPES medium with BSA (FHA), but increased both CHML and AGG of cells suspended in autologous plasma. Preincubation in FHA with LPS, 1 microgram/ml, for more than 15 min increased the OC of PMN activated with zymosan-activated plasma (ZAP) or n-formyl-methionyl-leu cyl-phenylalanine (FMLP) by more than 100%. A similar increase in the CHML of such cells was seen after FMLP, but not after ZAP. ZAP, however, primed the CHML response of the cells to subsequent activation with FMLP more than did preincubation with LPS. Previous exposure to both agents had an additive effect. Preincubation of PMN with LPS decreased the time interval from addition of phorbol myristate acetate (PMA) to peak OC response, but less so than previous activation with FMLP. Neither agent affected the maximal rate of OC after addition of PMA. LPS also increased the PMN aggregation induced by ZAP and FMLP, but not by PMA. Cells preincubated with LPS, 0.01 microgram/ml, increased their CHML in response to FMLP if suspended in Krebs-Ringer balanced salt solution, but not if suspended in FHA. Such preincubation had no effect on OC of similarly activated cells in any of the media. PMID- 8432565 TI - Pedestrian accidents on Merseyside: the case for criminalization of jaywalking. AB - During a 12-month review within Merseyside, 85 serious pedestrian accidents (ISS > 15 or death), were identified. Analysis of police accident statistics showed that 17 per cent of these cases had not been recorded. Children and the elderly made up 64 per cent of those injured. Accidents were more common in the afternoon and evening and evenly spread throughout the week. There was a low rate of alcohol testing among casualties who died and involved drivers. The majority of accidents occurred in good visibility and weather; 90 per cent were due to pedestrian behaviour. PMID- 8432564 TI - Role of oxygen intermediates in cytotoxicity: studies in chronic granulomatous disease. AB - The ability of human neutrophils to lyse various target cells was investigated using cells from normal individuals and from patients with chronic granulomatous disease (CGD) whose cells lack the ability to form reactive oxygen intermediates (ROI). Cytolysis was stimulated by phorbol myristate acetate (PMA), rabbit antiserum, and a heteroantibody that binds to both the FcRII receptor of neutrophils and to the target. The PMA-activated CGD neutrophils were deficient compared to controls in killing both tumor and chicken erythrocyte (CRBC) targets at all effector-target ratios in 18-h assays. When CRBC were sensitized with rabbit antiserum, the normal cells still killed slightly more. When killing of CRBC was mediated by the heteroantibody, however, cytotoxicity of CGD neutrophils exceeded that of normal cells. CGD mononuclear cells (MNC) killed tumor cell targets as well as or better than normal MNC. Thus, PMA-mediated cytolysis appears to depend primarily upon the ability of the cell to generate ROI whereas antibody-mediated cytotoxicity and MNC-mediated lysis of tumor cells do not require ROI formation. PMID- 8432566 TI - Scoring multitrauma patients: which scoring system? AB - Two methods of estimating the severity of injury and evaluating outcome, the Injury Severity Score (ISS) and the Polytrauma-Schlussel (PTS), were evaluated. The records of 37 victims of multiple injuries were assessed retrospectively by nine trauma surgeons using both methods of scoring. The agreement among the users was calculated by standard deviation. The standard deviation (SD) among users was smaller for the PTS (4.1) than for the ISS (6.2). Each method of scoring comprises six components contributing to the total score. The three highest scoring components of the ISS were first squared and then summated, the sum being the total ISS score. All the PTS categories were summated. Comparison of the SD for each of the components was not possible. However, the category or categories which mostly influenced the standard deviation could be indicated. For the ISS these were the circulation and central nervous system and for PTS, the limbs. We prefer the Polytrauma-Schlussel method because this takes account of age, needs revision of only one category and gives more consistent results among users. PMID- 8432567 TI - Contribution of preoperative investigations to the anaesthetic management of adult trauma patients. AB - In a prospective study of 50 adult trauma patients, the effects of a protocol calling for eight rapidly available special investigations and 11 laboratory, electrocardiographic and radiological investigations were assessed as to their influence on anaesthetic management. The only investigation which gave information additional to that obtained by the clinical examination was the arterial blood gas, especially the pH, arterial oxygen tension and arterial carbon dioxide tension. Other contributory investigations were the protocol haemoglobin and protocol blood sugar estimation. The protocol electrolytes and clotting profile as well as the laboratory full blood count, urea and electrolytes, electrocardiograph and chest radiograph did not make a contribution to the assessment and anaesthetic management of this patient group. PMID- 8432568 TI - Rupture of the ulnar collateral ligament of the metacarpophalangeal joint of the thumb. AB - The results after operations for rupture of the ulnar collateral ligament of the metacarpophalangeal joint of the thumb are reported to be good. Few authors describe the measurements used to assess the postoperative function of the thumb. We review the results of 15 patients, who underwent surgery between 1982 and 1987. We found that the number of patients satisfied with the operation was consistent with that reported in the literature. On the other hand, we found poor agreement between the subjective complaints and the objective findings. We therefore propose and describe a scoring system to assess subjective impressions of the result and the objective findings. Surgical procedures are not discussed. However, the duration of immobilization of the thumb should, perhaps, be reconsidered. Further studies may show that a shorter period of immobilization in plaster, the use of dynamic bandaging, or early starting of physiotherapy produce better results. PMID- 8432569 TI - Severe blunt assault injuries at Auckland Hospital. AB - The incidence and nature of severe blunt assault injury in the Auckland region was assessed by a retrospective review over a 2-year period. Approximately 14,000 charges of assault (excluding paediatric and sexual assault) were laid during this period. A total of 1035 people were admitted to hospital. Of 331 patients admitted to one hospital, 35 patients were admitted via the resuscitation room after severe assault; of these, two died. Of these patients, 33 were male and 19 of 21 ethanol levels measured were greater than 17 mmol/l. Head and facial injuries were the most frequent. PMID- 8432570 TI - Hip dislocation without fracture: traction or mobilization after reduction? AB - In all, 41 patients with traumatic dislocation of the hip, without associated acetabular or femoral fracture, were treated by two different methods after closed reduction, performed on average 2 h after injury. Patients in group A (N = 20) were subjected to skeletal traction for 2 weeks, followed by non-weight bearing for 3 months. Those in group B (N = 21) were mobilized a few days (average 9 days) after injury and allowed partial weight bearing. They were fully weight bearing at 3 months. The 31 patients were followed up for an average of 7.6 years and showed comparable long-term results in both groups. No early complications occurred in group B. There were no cases of avascular necrosis in either group. There were three cases of post-traumatic arthritis in group A and one in group B, and two cases each of heterotopic ossification. Early mobilization was concluded to be a safe and more comfortable method of after treatment. Earlier return to work was a significant benefit in Group B. PMID- 8432571 TI - Septic arthritis of the hand. PMID- 8432572 TI - Functional outcome after intertrochanteric fractures of the femur: does the implant matter? A prospective study of 100 consecutive cases. AB - In a randomized study of 100 consecutive patients with an intertrochanteric fracture of the femur fixed internally either with a sliding hip screw or with a McLaughlin nail-plate, the functional outcome of the 6 months survivors has been analysed. There was no statistically significant difference between the two treatment groups with regard to the rehabilitation progress and recovery to the prefracture walking ability, pain and gait at 6 months. Of the 6 months survivors, 55 per cent whose fractures were unstable and 76 per cent whose fractures were stable regained 90 per cent or more of their individual prefracture walking ability. The incidence of failure by 'cutting-out', the reoperation rate and the mortality at 6 months were not statistically different in the two treatment groups. PMID- 8432573 TI - Intra-articular fractures of the distal tibia: surgical management by limited internal fixation and articulated distraction. AB - A series of 12 patients with severe intra-articular (pilon) fractures of the distal tibia were treated by open reduction and internal fixation of the principal articular fragments. Tibial length was restored and maintained by an articulated external fixator which allowed early mobilization of the joint, and associated fibular fractures were fixed internally. Of the patients, nine have been followed up for an average of 33 months (range 18-60 months); three are still undergoing active treatment. Results have been assessed using the scoring system devised by Karlsson and Peterson. Four patients had scores > 80, four had scores between 50 and 79, and one had a score < 50. This technique is less invasive than conventional open procedures that require the use of a tibial plate and may be of particular value in the management of open fractures. PMID- 8432574 TI - Treatment of ipsilateral femoral shaft fractures and hip fractures. AB - Ipsilateral femoral shaft fractures and hip fractures are difficult to treat. The treatment protocols are diversified. We report the results of treating 16 such fractures. The diaphyseal fractures are fixed with intramedullary locked nails and the hip fractures with cannulated lag screws. The average follow-up period is 21.8 months. The results show that all diaphyseal fractures healed, one proximal fracture had delayed union. Functionally, 14 (87.5 per cent) patients had good results and two (12.5 per cent) had fair results; additional procedures may be necessary if the treatment of fractures is delayed. It is concluded that the present treatment protocol gives predictable good results for these fractures. The use of the newly available long gamma nail is also discussed and illustrated. PMID- 8432575 TI - The simple fix: external fixation of displaced isolated tibial fractures. AB - Eleven patients with an isolated and displaced tibial fracture were treated by external fixation with a simple device to provide mobile traction. Anatomical results were good and all fractures healed uneventfully with minimal morbidity. PMID- 8432576 TI - A new solid unreamed tibial nail for shaft fractures with severe soft tissue injury. AB - In a prospective study, 51 tibial shaft fractures with severe open or closed soft tissue damage were treated with a new, thin (8 mm or 9 mm) solid locking nail, inserted without reaming. At 6 months or more after trauma, 43 cases were reviewed. Fractures were classified according to Muller with six type A, 25 type B, and 12 type C fractures. In 13 cases there was group II (n = 8) or group III (n = 5) closed soft tissue damage (Tscherne). Of 30 open fractures, 16 were group OII, six were group OIIIA and eight were group OIIIB (Gustilo). Postoperative treatment in 42 of 44 cases was possible without additional cast or brace. Full weight bearing was achieved in 26 cases within 12 weeks, and in 42 cases within 26 weeks. In 43 cases, fracture healing occurred with a mean of 21.9 weeks (range 12-40 weeks). There was one case with valgus of 6 degrees and three cases with anterecurvatum deformities of 5 degrees to 10 degrees. In four cases there was an external rotation malalignment between 10 degrees and 20 degrees. In three cases we found an internal rotation deformity of 10 degrees to 20 degrees. Shortening between 0.5 and 1.0 cm was found in five cases, and in one case shortening was 1.5 cm. None of the patients had an osteomyelitis. PMID- 8432577 TI - The Victoria bomb: a report from the Westminster Hospital. AB - On 18 February 1991 a bomb exploded on Victoria station, London. A total of 51 people were injured including one fatally. Of the most seriously wounded, 30 were treated at The Westminster Hospital. The majority of injuries were to the lower limbs, but serious wounds were also sustained to the chest, abdomen, forearm, orbit and cranium. Almost all injuries were caused by shrapnel. The low incidence of infection was attributed to thorough early surgical debridement. The administration of antibiotics was varied and uncoordinated, reflecting a lack of a common policy. The exhaustion of common external fixators necessitated the use of equipment unfamiliar to the surgeons and underlined the need for the rapid transfer of equipment between hospitals at the time of major incidents. PMID- 8432578 TI - Classification and treatment of volar Barton fractures. AB - Results of treatment in 78 patients with volar Barton's fractures have been analysed. On radiological assessment these fractures were divided into three distinct categories and this classification is related to the results of closed manipulation. Results are best when this fracture is treated with open reduction and internal fixation. In non-operatively treated cases results are much better if the articular step is less than 2 mm. PMID- 8432579 TI - Liposuction for drainage of large haematoma. PMID- 8432580 TI - Femoral nerve palsy following a subperiosteal haematoma. PMID- 8432581 TI - Jejunal perforation in a football player. PMID- 8432582 TI - Gastric rupture from blunt trauma: two unusual presentations. PMID- 8432583 TI - Arterialized venous flap for covering and revascularizing finger injury. PMID- 8432584 TI - Escherichia coli heat-labile toxin subunit B fusions with Streptococcus sobrinus antigens expressed by Salmonella typhimurium oral vaccine strains: importance of the linker for antigenicity and biological activities of the hybrid proteins. AB - A set of vectors possessing the genes for aspartate semialdehyde dehydrogenase (asd) and the B subunit of the heat-labile enterotoxin of Escherichia coli (LT-B) has been developed. These vectors allow operon or gene fusions of foreign gene epitopes at the C-terminal end of LT-B. Two groups of vectors have been constructed with and without leader sequences to facilitate placing of the foreign antigen in different cell compartments. Two Streptococcus sobrinus genes coding for principal colonization factors, surface protein antigen A (SpaA), and dextranase (Dex), have been fused into the 3' end of the LT-B gene. Resulting protein fusions of approximately 120 to 130 kDa are extremely well recognized by antibodies directed against both SpaA and Dex as well as against LT-B domains and retain the enzymatic activity of dextranase and the biological activity of LT-B in that they bind to GM1 gangliosides. Maximum antigenicity was obtained with the vector possessing an intervening linker of at least six amino acids with two proline residues. Some of the fusion proteins also exhibited another property of LT-B in that they were exported into the periplasm where they oligomerized. LT-B SpaA and LT-B-Dex hybrid proteins are expressed stably and at a high level in avirulent Salmonella typhimurium vaccine strains which are being used to investigate their immunogenicity and types of induced immune responses. The fusion vectors will also be useful for production and purification of LT-B fusion antigens to be used and evaluated in other vaccine compositions. PMID- 8432585 TI - Laboratory and clinical evaluation of conjugate vaccines composed of Staphylococcus aureus type 5 and type 8 capsular polysaccharides bound to Pseudomonas aeruginosa recombinant exoprotein A. AB - The synthesis, standardization, and immunogenicity in young outbred mice and clinical evaluation in adult volunteers of investigational vaccines designed to induce serum antibodies to the type 5 and type 8 capsular polysaccharides (CPs) of Staphylococcus aureus are described. Conjugates composed of the type 5 CP and a sonicated preparation of a high-molecular-weight type 8 CP bound to a nontoxic recombinant protein derived from Pseudomonas aeruginosa exotoxin A (rEPA) were synthesized. The conjugates were nontoxic and elicited serum CP antibodies after two subcutaneous injections into young outbred mice; a third injection elicited a booster response. The lower-molecular-weight type 8 CP was not immunogenic in the mice, and the high-molecular-weight type 8 CP elicited low levels of antibodies without a booster effect. In the volunteers, neither the conjugates nor the type 8 CP alone caused significant local reactions or fever. The conjugates elicited type-specific antibodies of both the immunoglobulin M (IgM) and IgG classes after the first injection; a second injection 6 weeks later did not stimulate a booster effect. The high-molecular-weight type 8 CP alone, injected once only, elicited levels of IgG and IgM type-specific antibodies similar to those of the conjugate. The vaccine-induced CP antibodies were mostly of the IgG1 and IgG2 subclasses and had opsonophagocytic activity. The conjugates elicited IgG antibodies to the native exotoxin A with neutralizing activity. In summary, the type 5 and type 8 conjugates were safe and elicited biologically active antibodies to both the CP and rEPA components. PMID- 8432586 TI - Lipopolysaccharide-binding proteins of Limulus amebocyte lysate. AB - Limulus amebocyte lysate, obtained from horseshoe crab (Limulus polyphemus) blood cells, contains a coagulation system which is activated by bacterial lipopolysaccharide (LPS). A chromatographic fraction of Limulus lysate, containing the endotoxin-sensitive factor(s) which initiates the coagulation cascade, was studied. We utilized a photoreactive, cleavable, radiolabeled derivative of Salmonella minnesota LPS, LPS-(p-azidosalicylamido)-1,3' dithiopropionamide (LPS-ASD), to identify LPS-binding proteins. The lysate fraction was incubated with LPS-ASD, and LPS-binding proteins were identified by autoradiography of sodium dodecyl sulfate-polyacrylamide gels. An 82-kDa protein, a major protein component of this fraction from Limulus lysate, was identified as a LPS-binding protein in a majority of lysates. Incubation of whole Limulus lysate with antiserum to this protein resulted in enhanced sensitivity of the lysate to LPS, suggesting that this 82-kDa protein is a negative regulator of coagulation. A minor 50-kDa protein component of lysate also was identified as a LPS-binding protein and is a candidate for the LPS-sensitive coagulation protein in L. polyphemus. PMID- 8432587 TI - Localization of myosin heavy chain A in the human pathogen Entamoeba histolytica. AB - To recognize myosin II in trophozoites of the human pathogen Entamoeba histolytica, a specific antimyosin polyclonal serum was raised against a fusion protein consisting of a 146-amino-acid fragment of the myosin II heavy chain A of E. histolytica (MhcA) fused with beta-galactosidase. The hybrid protein was encoded by a chimera gene formed by a DNA fragment, from the mhcA gene, amplified by polymerase chain reaction and fused with the lacZ gene of Escherichia coli. Polymerase chain reaction-amplified DNA is located within the region encoding the tail domain of myosin. This antibody recognized a 250-kDa protein in extracts of E. histolytica trophozoites. Confocal microscope analysis of antibody-labelled trophozoites indicated that MhcA localizes at the posterior pole of locomoting cells and concentrates within the uroid. These results might indicate that MhcA is involved in movement and in the uroid formation which help amoebas to escape the host immune response. These data are the first evidence indicating that myosin exists in E. histolytica. In addition, two other peptides were found in myosin-enriched extracts of amoebas, indicating that other myosins may be present in this parasite. PMID- 8432588 TI - Leishmania donovani-reactive Th1- and Th2-like T-cell clones from individuals who have recovered from visceral leishmaniasis. AB - Infections in humans by Leishmania donovani parasites can result in a fatal disease, visceral leishmaniasis (VL), or in a self-limiting asymptomatic infection. In murine models of the infection employing Leishmania major, the course of the disease can be directed into a VL-like syndrome by interleukin-4 (IL-4)-producing Th2 cells, or cure may result by Th1 cells secreting gamma interferon (IFN-gamma). The present study examined the potential of human T cells to generate Th1 or Th2 responses to L. donovani. The profiles of IFN-gamma, IL-4, and lymphotoxin secretion after antigen stimulation were analyzed in a panel of L. donovani-reactive CD4+ human T-cell clones generated from individuals who had recovered from VL after antimonial treatment. Two of the T-cell clones produced large amounts of IL-4 without production of IFN-gamma, seven clones produced both IFN-gamma and IL-4, and eight produced only IFN-gamma. This is the first report of a Th1- and Th2-type response in human leishmaniasis. These results suggest that in analogy with murine models, there is a dichotomy in the human T-cell response to L. donovani infections. Preferential activation of IL-4-producing Th2 like cells may be involved in the exacerbation of human VL, whereas activation of IFN-gamma-producing Th1 cells may protect the host from severe disease. Identification of leishmanial antigens activating one or the other type of T cells will be important in the development of vaccines against leishmaniasis. PMID- 8432589 TI - Nucleotide sequence analysis and serologic characterization of a 27-kilodalton Mycobacterium intracellulare lipoprotein. AB - Disseminated mycobacteremia resulting from Mycobacterium avium-Mycobacterium intracellulare complex (MAC) infections frequently contribute to the morbidity and mortality seen in AIDS patients. To better understand the immunopathology of MAC disease and to identify molecules that may have potential diagnostic and vaccine utility, an immunoreactive M. intracellulare protein (MI43) and the gene encoding this antigen were characterized. Southern blot hybridizations demonstrated that MI43 gene probes reacted only with genomic DNA from M. intracellulare, M. avium, and Mycobacterium asiaticum and not with DNA isolated from 11 other mycobacterial species. Nucleotide sequence analysis showed that the MI43 gene encodes a 27-kDa protein which contains a consensus bacterial lipoprotein processing sequence. Detergent-phase separations and metabolic labeling with [3H]palmitate also suggested that MI43 is a lipoprotein. Serological assays demonstrated that recombinant MI43 fusion proteins react with sera from M. avium-infected mice, sera from patients with MAC disease, and sera from patients with active tuberculosis. These results further suggest that mycobacterial lipoproteins are important immunogens that should be considered in the development of improved mycobacterial vaccines and diagnostic reagents. PMID- 8432590 TI - Effects of Clostridium difficile toxin B on human monocytes and macrophages: possible relationship with cytoskeletal rearrangement. AB - Toxin B from Clostridium difficile is cytopathic in vitro for various types of cells, including polymorphonuclear cells, lymphocytes, and monocytes. Since intestine lamina propria is rich in macrophages, we studied the effect of toxin B on human monocytes and on human macrophages generated in vitro by long-term culture of purified circulating blood monocytes. Upon addition of toxin B, human monocytes exhibited few modifications whereas macrophages adopted a stellate morphology, with rounding up of the perikaryon. Toxin B made microfilaments of actin disappear and induced an important reorganization of vimentin and a redistribution of tubulin. Membrane area increased by approximately 16%. Toxin B did not affect the viability of human mononuclear phagocytes and did not exert any significant lytic effect. It profoundly altered the phagocytic function of macrophages. When activated by gamma interferon in the presence of toxin B, monocytes were more cytotoxic for U-937 target cells than control monocytes activated in absence of toxin. Finally, the combined treatment of monocytes with gamma interferon and toxin B increased significantly the secretion of tumor necrosis factor alpha, whereas toxin B alone was unable to induce tumor necrosis factor production. These results suggest that morphological and functional alterations induced in human mononuclear phagocytes by toxin B from C. difficile are due to the disorganization of the cytoskeleton and the resulting impairment of the membrane traffic equilibrium. PMID- 8432591 TI - Genetic conservation of hlyA determinants and serological conservation of HlyA: basis for developing a broadly cross-reactive subunit Escherichia coli alpha hemolysin vaccine. AB - The HlyA determinant among Escherichia coli isolates from patients with symptomatic urinary tract infection was compared in this report with a prototype HlyA encoded by pSF4000 by DNA-DNA hybridization tests with 20-base synthetic oligonucleotides and monoclonal antibody binding and neutralization assays. Hybridization results demonstrated that 349 (98%) of 357 definitive reactions among 54 hemolytic strains shared homology with seven DNA probes spanning many HlyA regions corresponding to residues (R) 41 to 47, 55 to 61, 248 to 254, 306 to 312, 336 to 343, 402 to 408, and 929 to 935. Genetic divergence was identified by lack of hybridization signals among 17 to 76% of the hemolytic strains within the distal portion of a predicted hydrophobic region corresponding to R491 to 319 and within a predicted hydrophilic region corresponding to R491 to 497 and R532 to 538. Serological studies demonstrated that 26 (81%) culture supernatants of 32 hemolytic strains were bound by all 12 monoclonal anti-HlyA antibodies. Among five of six remaining strains, the culture supernatants were bound by 3 to 11 monoclonal antibody preparations. There was only one hemolytic culture supernatant that failed to be bound by any monoclonal antibody, although the strain hybridized with nine hemolysin DNA probes. In addition, hemolytic activity of all 24 different culture supernatants tested was reduced by at least twofold by one monoclonal antibody specific for R2-161. These data extend and support previous views that the HlyA determinant is conserved among E. coli strains and suggest that a broadly cross-reactive HlyA subunit vaccine can be developed. PMID- 8432592 TI - Comparison of Shiga-like toxin I B-subunit expression and localization in Escherichia coli and Vibrio cholerae by using trc or iron-regulated promoter systems. AB - Shiga-like toxin I (SLT-I) B-subunit expression was examined by using the trc promoter in two different constructs, pSBC32 and pSBC54, in which 710 bp of DNA downstream of the B subunit in pSBC32 was deleted. The trc promoter in pSBC54 was replaced also with the SLT-I iron-regulated promoter to create a third plasmid, pSBC61. SLT-I B-subunit expression was examined from all three plasmids following transfer into Escherichia coli JM105 and the cholera toxin A-subunit gene deletion mutant Vibrio cholerae 0395-N1. The SLT-I B subunit was expressed from all constructs. pSBC61 was regulated by elemental iron and produced equivalent amounts of SLT-I B subunit from both E. coli and V. cholerae. In contrast to the cholera toxin B subunit, virtually all released into the medium, the SLT-I B subunit was predominantly cell associated in the pSBC61 constructs. Both pSBC32 and pSBC54 were inducible with isopropyl-beta-D-thiogalactopyranoside (IPTG) in the E. coli background but not the V. cholerae background; however, when E. coli cultures were allowed to grow for 24 h, the yield of SLT-I B subunit was not increased by IPTG induction. Both pSBC32 and -54 expressed more SLT-I B subunit in the V. cholerae host than in the E. coli host. Scale-up to a 9.9-liter fermentor culture of V. cholerae 0395 N1 (pSBC32) resulted in the isolation of 220 mg of SLT-I B. The purified B subunit was identical, in terms of binding to Vero cells, stoichiometry after chemical cross-linking, and ability to inhibit cytotoxicity of intact Shiga toxin, to native SLT-I B subunit from E. coli O157:H7. PMID- 8432593 TI - Listeria monocytogenes infection in beta 2 microglobulin-deficient mice. AB - beta 2 microglobulin-deficient mice, in which the beta 2m gene has been disrupted by homologous recombination, lack functional CD8 T cells and are able to contain but not resolve an intravenous immunizing inoculum of Listeria monocytogenes. We present evidence that compensatory immunity in such immunodeficient mice was mediated by a population of gamma delta T-cell receptor-positive cells; in contrast, neither CD4 cells nor natural killer cells appeared to play any part in this process. These data further support the emerging hypothesis that immune cells other than those bearing the alpha beta T-cell receptor type can also play an important role in acquired resistance to listeriosis. PMID- 8432594 TI - Cloning and expression of the multiple sugar metabolism (msm) operon of Streptococcus mutans in heterologous streptococcal hosts. AB - The multiple sugar metabolism (msm) operon of Streptococcus mutans is responsible for the uptake and metabolism of a variety of sugars. In order to further characterize the substrate specificities of the transport system, a 12-kb region of DNA containing the entire msm operon was cloned, via a novel two-step integration strategy, into the chromosomes of two heterologous streptococcal strains, Streptococcus gordonii Challis and Streptococcus anginosus Is57, as well as the chromosome of a natural isolate of S. mutans with a deletion of the msm region. These strains are unable to transport or ferment melibiose, raffinose, or isomaltosaccharides, but the newly constructed recombinants gained the ability to ferment all of these sugars. The S. gordonii Challis construct containing msm was shown to transport radiolabelled melibiose, raffinose, isomaltotriose, and isomaltotetraose, and the transport function was also subjected to induction by raffinose, an inducer of the msm operon in S. mutans. The results confirm the role of the msm operon in the transport and metabolism of melibiose, raffinose, and isomaltosaccharides. PMID- 8432595 TI - Molecular cloning, expression, and DNA sequence analysis of the gene that encodes the 16-kilodalton outer membrane lipoprotein of Serpulina hyodysenteriae. AB - The gene (smpA) that encodes the 16-kDa outer membrane lipoprotein of Serpulina hyodysenteriae was cloned in Escherichia coli, and its primary structure was determined by nucleotide sequencing. The putative open reading frame encodes a prolipoprotein of 16.8 kDa which in its fully acylated and cleaved form is 15.1 kDa. Analysis of the N-terminal amino acid sequence derived from the DNA sequence revealed the presence of a signal sequence and a putative acylation and signal peptidase II cleavage site (Phe-Ala-Val-Ser-Cys). In E. coli, processing of the prolipoprotein was less efficient than that observed in S. hyodysenteriae, and globomycin, an inhibitor of signal peptidase II, inhibited cleavage of the lipoprotein expressed in E. coli but did not inhibit cleavage in S. hyodysenteriae. PMID- 8432596 TI - Induction of bradyzoite-specific Toxoplasma gondii antigens in gamma interferon treated mouse macrophages. AB - By using stage-specific monoclonal antibodies, an in vitro model has been developed to analyze the kinetics of expression of stage-specific antigens during the conversion process between tachyzoites and bradyzoites of Toxoplasma gondii. Following infection of murine macrophages with bradyzoites, the expression of bradyzoite-specific antigens declined, whereas the expression of tachyzoite specific antigens increased during the first 72 h postinfection. Conversely, in gamma interferon-treated murine macrophages infected with tachyzoites, the inhibitory effect of gamma interferon on replication of parasites was accompanied by the induction of bradyzoite-specific antigens. PMID- 8432597 TI - Safety and immunogenicity of Salmonella typhi Ty21a vaccine in young Thai children. AB - Salmonella typhi Ty21a vaccine in a liquid formulation was evaluated in 634 Thai children 2 to 6 years of age. The seroconversion rate was 69% for those who received vaccine versus 14% for those who received placebo (P < 0.005). The immune responses among vaccine recipients ranged from 60% in 3-year-olds to 81% for 6-year-olds. PMID- 8432598 TI - Attaching-effacing lesions and intracellular penetration in HeLa cells and human duodenal mucosa by two Escherichia coli strains not belonging to the classical enteropathogenic E. coli serogroups. AB - In the present study, we compared two strains of serotypes O88:H25 and O145:H45 with an enteropathogenic Escherichia coli (EPEC) adherence factor-positive (EAF+) strain of the classic enteropathogenic E. coli serotype O111ab:H2 for their association with HeLa cells and with biopsies of human duodenal mucosa. Both strains not belonging to the classic EPEC serotype showed virulence properties similar to those of the serotype O111ab:H2 strain, i.e., the production of attaching-effacing lesions and intracellular penetration in both systems. These virulence properties associated with the relatively high frequency at which the two serotypes had been detected in infant diarrhea in Sao Paulo, Brazil (T. A. T. Gomes, M. A. M. Vieira, I. K. Wachsmuth, P. A. Blake, and L. R. Trabulsi, J. Infect. Dis. 160:131-135, 1989) allowed us to suggest that strains of serotypes O88:H25 and O145:H45 should be included in the EAF+ EPEC category. PMID- 8432599 TI - Immunolocalization of superoxide dismutase in Dirofilaria immitis adult worms. AB - Superoxide dismutase (SOD) may not only perform a housekeeping role in filarial worms but also assist in defense against oxidants generated by host immune cells. Both Dirofilaria and Onchocerca adult filariae and microfilariae contain relatively high activities of the antioxidant enzyme SOD; adult Dirofilaria worms also secrete SOD in vitro. In addition, superoxide radicals are relatively impotent against Dirofilaria and Onchocerca microfilariae in vitro. In assessing the role of SOD, we determined the anatomic localization of SOD in D. immitis adult worms by immunolocalization at the light-microscopic level. We found that anti-D. immitis SOD did not stain parasite tissues homogeneously, in support of the hypothesis that SOD does not have only a housekeeping role and that the pattern of staining may suggest another role(s) for SOD. PMID- 8432600 TI - Toxicity of recombinant toxic shock syndrome toxin 1 and mutant toxins produced by Staphylococcus aureus in a rabbit infection model of toxic shock syndrome. AB - Menstrually associated toxic shock syndrome (TSS) is attributed primarily to the effects of staphylococcal exotoxin toxic shock syndrome toxin 1 (TSST-1). A region of the 194-amino-acid toxin spanning residues 115 through 144 constitutes a biologically active site. Several point mutations in the TSST-1 gene in that region result in gene products with reduced mitogenic activity for murine T cells. In this study we evaluated the toxicity of recombinant TSST-1 and several mutants of TSST-1 made by transformed Staphylococcus aureus during in vivo growth in a rabbit infection model of TSS. The toxicities of the transformed strains of S. aureus for rabbits correlated with the mitogenic activities of the recombinant toxins. An isolate originally obtained from a patient with a confirmed case of TSS (S. aureus 587) implanted in a subcutaneous chamber served as a positive control. TSST-1 produced in vivo led to lethal shock within 48 h, and a TSST-1 neutralizing antibody (monoclonal antibody 8-5-7) administered to rabbits challenged with S. aureus 587 prevented fatal illness. Rabbits infected with transformed S. aureus RN4220 expressing wild-type toxin (p17) or mutant toxins retaining mitogenic activity for T cells succumbed within a similar time frame. Blood chemistries of samples obtained from infected animals before death indicated abnormalities in renal and hepatic functions similar to those induced by parenteral injection of purified staphylococcal TSST-1. Mutant toxin 135 (histidine modified to alanine at residue 135) possessed only 5 to 10% of the mitogenic activity of wild-type toxin. Rabbits challenged with transformed S. aureus RN4220 expressing mutant toxin 135 exhibited only mild transient illness. Mutant toxin 135 retained reactivity with monoclonal antibody 8-5-7 and by several criteria was conformationally intact. Toxin from a double mutant, 141.144, with alanine substitutions at residues 141 (histidine) and 144 (tyrosine), also was devoid of mitogenic activity. In this case, antibody recognition was lost. Mutant toxins 115 and 141 were found to possess approximately half-maximal mitogenic activity. Rabbits challenged with S. aureus RN4220 expressing either 115 or 141 toxin succumbed to lethal shock. We conclude that the ability of TSST-1 to activate murine T cells in vitro and its expression of toxicity leading to lethal shock in rabbits are related phenomena. PMID- 8432601 TI - Characterization of environmental regulators of Bordetella pertussis. AB - Bordetella pertussis suppresses transcription of its virulence genes in response to specific environmental conditions, a response called modulation. The organism responds to high concentrations of SO4 and CIO4 ions, nicotinic acid, and nicotinic acid analogs in vitro; however, the in vivo modulator has not been identified. We investigated which chemical structures of the nicotinic acid molecule are important for modulation by testing various analogs for their ability to modulate. The ring nitrogen of nicotinic acid was not required, since benzoic acid was a modulator. In contrast, the carboxyl group was required, since derivatives like ethylnicotinate, 3-pyridylcarbinol, 3-acetyl pyridine, and 6 chloronicotinamide with altered carboxyl groups were not modulators. The planar ring structure or resonance in the ring was required for modulation, since nipecotic acid failed to modulate. The most potent modulators were nicotinic acid derivatives with electron-withdrawing substituents in the meta or para position relative to the carboxyl group. Relative hydrophilicity of substituents did not appear to contribute to modulation. Although these modulators elicited a clear biological response, the mechanism of modulation remains unclear, because no binding of the modulator 35SO4 or [14C]4-chlorobenzoic acid to whole B. pertussis was detected. However, modulation appears to involve a charge-charge interaction, since the response was blocked by chlorine ions. PMID- 8432602 TI - Possible origin of sequence divergence in the P1 cytadhesin gene of Mycoplasma pneumoniae. AB - Specific regions of the P1 adhesin structural gene of Mycoplasma pneumoniae hybridize to various parts of the mycoplasma genome, indicating their multiple copy nature. In addition, restriction fragment length polymorphisms and sequence divergence have been observed in the P1 gene, permitting the classification of clinical isolates of M. pneumoniae into two groups, I and II. These data suggest that the observed P1 gene diversity may be explained by homologous recombination between similar but not identical multicopy P1-related sequences and the P1 structural gene. We used oligonucleotide probes specific to the diverged regions of the group I and group II P1 structural genes to clone and sequence multicopy P1-related DNA segments. We detected sequences in group I M. pneumoniae isolates that were homologous not only to the group I P1 structural gene but also to the diverged regions of the group II P1 structural gene. Likewise, sequences in group II clinical isolates that were homologous both to the group II P1 structural gene and the diverged regions of the group I P1 structural gene were detected. PMID- 8432603 TI - T-cell-independent resistance to infection and generation of immunity to Francisella tularensis. AB - The intraperitoneal 50% lethal dose (LD50) for Francisella tularensis LVS in both normal control heterozygote BALB/c nu/+ mice and BALB/c nu/nu mice was 2 x 10(0). Both nu/+ and nu/nu mice given 10(7) LVS bacteria or more intradermally (i.d.) died, with a mean time to death of about 7 to 8 days. On the other hand, nu/+ mice given 10(6) LVS bacteria or less survived for more than 60 days and cleared systemic bacteria, while nu/nu mice given 10(6) LVS bacteria or less survived for more than 10 days but died between days 25 and 30. Thus, the short-term (i.e., < 10-day) i.d. LD50 of both nu/nu and nu/+ mice was 3 x 10(6), but the long-term (i.e., > 10-day) i.d. LD50 of nu/nu mice was less than 7 x 10(0). The short-term survival of i.d. infection was dependent on tumor necrosis factor and gamma interferon: treatment of nu/nu mice with anti-tumor necrosis factor or anti-gamma interferon at the time of i.d. infection resulted in death from infection 7 to 8 days later, whereas control infected nu/nu mice survived for 26 days. nu/nu mice infected with LVS i.d. generated LVS-specific serum antibodies, which were predominantly immunoglobulin M: titers peaked 7 days after i.d. infection but declined sharply by day 21, after which mice died. Surprisingly, nu/nu mice given 10(3) LVS bacteria i.d. became resistant to a lethal challenge (5,000 LD50s) of LVS intraperitoneally within 2 days after i.d. infection; nu/nu mice similarly infected with LVS i.d. and challenged with Salmonella typhimurium (10 LD50s) were not protected. nu/nu mice given nu/+ spleen cells intravenously as a source of mature T cells survived i.d. infection for more than 60 days and cleared bacteria. Taken together, these studies demonstrate that i.d. infection of nu/nu mice with LVS rapidly generates T-cell-independent, short-term, specific protective immunity against lethal challenge, but T lymphocytes are essential for long-term survival. PMID- 8432604 TI - Specificity of a protective memory immune response against Mycobacterium tuberculosis. AB - We have investigated the memory T-cell immune response to Mycobacterium tuberculosis infection. C57BL/6J mice infected with M. tuberculosis were found to generate long-lived memory immunity which provided a heightened state of acquired resistance to a secondary infection. The T-cell response of memory immune mice was directed to all parts of the bacilli, i.e., both secreted and somatic proteins. Major parts of the memory T-cell repertoire were maintained in a highly responsive state by cross-reactive restimulation with antigens present in the normal microbiological environment of the animals. A resting non-cross-reactive part of the memory repertoire was restimulated early during a secondary infection to expand and produce large amounts of gamma interferon. The molecular target of these T cells was identified as a secreted mycobacterial protein with a molecular mass of 3 to 9 kDa. PMID- 8432605 TI - C1q binding and activation of the complement classical pathway by Klebsiella pneumoniae outer membrane proteins. AB - The mechanisms of killing of Klebsiella pneumoniae serum-sensitive strains in nonimmune serum by the complement classical pathway have been studied. The bacterial cell surface components that bind C1q more efficiently were identified as two major outer membrane proteins, presumably the porins of this bacterial species. These two outer membrane proteins were isolated from a representative serum-sensitive strain. We have demonstrated that in their purified form, they bind C1q and activate the classical pathway in an antibody-independent manner, with the subsequent consumption of C4 and reduction of the serum total hemolytic activity. Activation of the classical pathway has been observed in human nonimmune serum and agammaglobulinemic serum (both depleted in factor D). Binding of C1q to other components of the bacterial outer membrane, in particular the rough lipopolysaccharide, could not be demonstrated. Activation of the classical pathway by this lipopolysaccharide was also much less efficient than activation by the two outer membrane proteins. The antibody-independent binding of C1q to serum-sensitive strains was independent of the presence of capsular polysaccharide, while strains possessing lipopolysaccharide O antigen bind less C1q and are resistant to complement-mediated killing. PMID- 8432606 TI - In vitro killing of Ehrlichia risticii by activated and immune mouse peritoneal macrophages. AB - Normal resident murine peritoneal macrophages inoculated in vitro with Ehrlichia risticii readily phagocytized the organism but were unable to suppress ehrlichial replication as determined by indirect fluorescent-antibody staining of the inoculated cells. In contrast, macrophages from Corynebacterium parvum-inoculated and E. risticii-recovered mice rapidly eliminated the ehrlichiae. Macrophages from E. risticii-recovered mice were as effective as the C. parvum-activated cells in phagocytizing and eliminating the organism. Opsonization of E. risticii with homologous antiserum prior to inoculation of macrophage cultures resulted in enhancement of phagocytosis and greater suppression of E. risticii replication in all macrophage groups. These findings indicate that the pathogenesis of E. risticii infection centers on the ability of the organism to enter and replicate within the macrophage with avoidance of macrophage antimicrobial effects. An immune response results in macrophage activation with enhancement of the macrophage's ability to eliminate E. risticii. Opsonization of E. risticii with anti-E. risticii serum renders E. risticii more susceptible to macrophage destruction. PMID- 8432607 TI - Murine peritoneal macrophages activated by the mycobacterial 65-kilodalton heat shock protein express enhanced microbicidal activity in vitro. AB - After an intraperitoneal (i.p.) injection of purified protein derivative, peritoneal macrophages from mice infected with Mycobacterium bovis bacillus Calmette-Guerin (BCG) show an enhanced respiratory burst, inhibit the intracellular proliferation of Toxoplasma gondii, and kill Listeria monocytogenes more efficiently than peritoneal macrophages from normal mice. One of the immunodominant antigens of Mycobacterium spp. is the 65-kDa heat shock protein (Hsp 65), and in the present study, we determined whether injection of this protein into mice leads to activation of their peritoneal macrophages. After an i.p. injection of Hsp 65, peritoneal macrophages from BCG-infected CBA/J mice also released more H2O2, inhibited the proliferation of T. gondii, and killed L. monocytogenes faster than peritoneal macrophages from normal mice, although Hsp 65 was less effective than purified protein derivative. When normal mice were injected with Hsp 65 suspended in saline after a booster injection with Hsp 65, their macrophages did not display enhanced antimicrobial activity, indicating that an adjuvant was required for a cellular immune response against Hsp 65. In the present study, the adjuvant dimethyl dioctadecylammonium bromide (DDA) was preferred because it contains no endotoxin or mycobacterial antigens and because it has been reported that DDA does not induce the production of gamma interferon. Peritoneal macrophages from C57BL/6 and CBA/J mice that had received a subcutaneous injection of Hsp 65 suspended in DDA followed by an i.p. booster injection of Hsp 65 suspended in saline were activated, as indicated by the enhanced production of H2O2, inhibition of the intracellular proliferation of T. gondii, and increased rate of intracellular killing of L. monocytogenes in vitro relative to that by resident peritoneal macrophages and peritoneal macrophages obtained from mice that had received ovalbumin instead of Hsp 65. The rate of phagocytosis of L. monocytogenes was not affected by Hsp 65 treatment. Despite the in vitro expression of enhanced microbicidal activity of peritoneal macrophages, no difference in the growth of L. monocytogenes in the liver and spleen between Hsp 65-treated and control mice was found. PMID- 8432608 TI - In vitro model of adhesion and invasion by Bacillus piliformis. AB - An in vitro model of Bacillus piliformis infection was developed to investigate the mechanisms of adhesion and internalization of this obligate intracellular bacterium. Adhesion and internalization events were examined by electron microscopic evaluation of infected Caco-2 cell monolayers. A few bacteria were identified in apical surface invaginations and in vacuoles subjacent to the apical surface, whereas the majority of bacteria were observed free within the cytoplasm, suggesting that B. piliformis entered epithelial cells via a phagocytic process and rapidly escaped the phagosome. To confirm that host cell phagocytosis was involved in entry of B. piliformis into mammalian cells, Intestine 407 cells were treated with the phagocytic inhibitor cytochalasin D, infected with B. piliformis, and evaluated for bacterial internalization by double-fluorescence labeling. The results showed decreased intracellular bacteria, suggesting that internalization was dependent on host cell microfilament function. To examine the role of B. piliformis in internalization, growth of live and Formalin-killed bacteria was compared. Dead bacteria were not internalized, suggesting that B. piliformis actively participates in internalization. B. piliformis appears to enter host cells by a bacterially directed phagocytic process. The in vitro system described should prove invaluable in further investigations of B. piliformis pathogenic mechanisms. PMID- 8432609 TI - Conservation of antigen components from two recombinant hybrid proteins protective against malaria. AB - Recently, we have shown that two hybrid proteins carrying partial sequences of the blood-stage antigens SERP, HRPII, and MSAI from Plasmodium falciparum confer protective immunity on Aotus monkeys against an experimental parasite infection (B. Knapp, E. Hundt, B. Enders, and H. A. Kupper, Infect. Immun. 60:2397-2401, 1992). The malarial components of the hybrid proteins consist of amino acid residues 630 to 892 of SERP, amino acid residues 146 to 260 of MSAI, and the 189 C-terminal residues of HRPII. We have studied the diversity of these protein regions in field isolates of P. falciparum. Genomic DNA was extracted from the blood of six donors from two different areas where malaria is endemic. The gene regions of SERP and MSAI coding for the corresponding sequences of the protective hybrid proteins and the exon II region of the HRPII gene were amplified by polymerase chain reaction and sequenced. All three regions were found to be highly conserved. In the 262-amino-acid fragment of SERP, one single conservative amino acid substitution was found. The exon II region of HRPII showed only a slight variability in number and arrangement of the repeat units. The 115-amino acid fragment of MSAI which is located within an N-terminal region known to be conserved among different parasite strains was shown to be the most variable among the vaccine components: amino acid substitutions were found in 14 different positions of this MSAI region when both laboratory strains and field isolates were compared. PMID- 8432610 TI - Molecular cloning of a member of the gene family that encodes pMGA, a hemagglutinin of Mycoplasma gallisepticum. AB - A hemagglutinin with an M(r) of 67,000 (pMGA) from Mycoplasma gallisepticum S6 was purified by using monoclonal antibody affinity chromatography. Purified pMGA was treated with a number of enzymes, the resultant peptides were purified, and their amino acid sequence was determined by using an Applied Biosystems (model 471A) protein sequencer. The DNA sequence encoding two peptides was used to dictate the sequences of synthetic oligonucleotides which were used to screen a library of EcoRI-cut M. gallisepticum DNA in pUC18. A clone reactive to both probes was isolated and found to contain a recombinant insert of 10 kb. The clone was mapped by using restriction endonucleases and fragments subcloned into pUC18 for DNA sequencing. Analysis of part of the DNA sequence revealed an open reading frame containing 1,941 nucleotides which encoded 647 amino acids. The amino terminus was preceded by a putative leader sequence of 25 amino acids. A promoter region preceding the putative start codon GUG was also located. This gene would encode a mature protein of 67,660 Da. There were a number of differences between the predicted amino acid sequence and that determined by direct peptide sequencing. Also, two tryptic peptides of pMGA were not found in the DNA sequence. This suggested that the cloned gene did not encode pMGA but did encode a homolog (pMGA1.2). Furthermore, downstream of pMGA1.2 was a region of DNA encoding a leader sequence followed by an amino acid sequence with high homology to that encoded by the pMGA1.2 gene. The presence within M. gallisepticum of a family of pMGA genes is inferred from the DNA sequence and Southern transfer data. A possible role for this gene family in immune evasion is discussed. PMID- 8432611 TI - Characterization of specific binding of a human immunoglobulin M monoclonal antibody to lipopolysaccharide and its lipid A domain. AB - The human immunoglobulin M monoclonal antibody HA-1A was first described as an antibody which bound specifically to the lipid A region of lipopolysaccharide (LPS) (N. N. H. Teng, H. S. Kaplan, J. M. Herbert, C. Moore, H. Douglas, A. Wunderlich, and A. Braude, Proc. Natl. Acad. Sci. USA 82:1790-1794, 1985) and provided significant protection when administered to patients with gram-negative bacteremia and shock (E. J. Ziegler, C. J. Fisher, Jr., C. L. Sprung, R. C. Straube, J. C. Sadoff, G. E. Foulke, C. H. Wortel, M. P. Fink, R. P. Dellinger, N. N. H. Teng, I. E. Allen, H. J. Berger, G. L. Knatterud, A. F. LoBuglio, C. R. Smith, and the HA-1A Sepsis Study Group, New Engl. J. Med. 324:429-436, 1992). Since that original report, questions have arisen in the scientific literature concerning the specificity of this antibody in LPS and/or lipid A binding. Experiments have, therefore, been carried out with a variety of assay formats to determine the capacity of this HA-1A antibody to bind to lipid A and LPS. Direct binding experiments with a sensitive enzyme-linked immunosorbent assay (ELISA) system have established that HA-1A will bind to purified lipid A from both Escherichia coli and Salmonella spp. These results have been confirmed by using a fluid-phase antigen-antibody competitive inhibition assay with purified lipid A and an antibody-antibody competitive inhibition assay with a monoclonal antibody with known specificity for lipid A. The HA-1A monoclonal antibody has also been shown to bind to a panel of R-chemotype LPS by ELISA and, unlike many other previously reported anti-lipid A antibodies, binding of HA-1A to R-chemotype LPS and lipid A is comparable. Although binding of HA-1A to S-LPS (smooth, wild-type LPS) could not be detected by direct ELISA, competitive inhibition experiments with some preparations of S-LPS have been able to show specific HA-1A binding. Collectively, these data confirm the binding specificity of HA-1A for the lipid A component of LPS and provide evidence that this monoclonal antibody manifests a relatively uncommon profile in its capacity to bind lipid A and R-chemotype LPS as well as some preparations of S-LPS. PMID- 8432612 TI - Phenotypic characterization of xpr, a global regulator of extracellular virulence factors in Staphylococcus aureus. AB - We recently described a Tn551 insertion in the chromosome of Staphylococcus aureus S6C that resulted in drastically reduced expression of extracellular lipase (M. S. Smeltzer, S. R. Gill, and J. J. Iandolo, J. Bacteriol. 174:4000 4006, 1992). The insertion was localized to a chromosomal site (designated omega 1058) distinct from the lipase structural gene (geh) and the accessory gene regulator (agr), both of which were structurally intact in the lipase-negative (Lip-) mutants. In this report, we describe a phenotypic comparison between strains S6C, a hyperproducer of enterotoxin B; KSI9051, a derivative of S6C carrying the Tn551 insertion at omega 1058; ISP546, an 8325-4 strain that carries a Tn551 insertion in the agr locus; and ISP479C, the parent strain of ISP546 cured of the Tn551 delivery plasmid pI258repA36. Compared with their respective parent strains, ISP546 and KSI9051 produced greatly reduced amounts of lipase, alpha-toxin, delta-toxin, protease, and nuclease. KSI9051 also produced reduced amounts of staphylococcal enterotoxin B. Coagulase production was increased in ISP546 but not in KSI9051. Using a mouse model, we also demonstrated that ISP546 and KSI9051 were far less virulent than ISP479C and S6C. We have designated the genetic element defined by the Tn551 insertion at omega 1058 xpr to denote its role as a regulator of extracellular protein synthesis. We conclude that xpr and agr are similar and possibly interactive regulatory genes that play an important role in pathogenesis of staphylococcal disease. PMID- 8432613 TI - The interleukin-1 receptor antagonist can either reduce or enhance the lethality of Klebsiella pneumoniae sepsis in newborn rats. AB - Klebsiella pneumoniae, a worldwide cause of nosocomial infections, is one of the most common causes of death in newborns in nurseries. In this study, we investigated the role of interleukin-1 (IL-1) in an experimental animal model of neonatal sepsis, using a natural antagonist of IL-1 receptors, the IL-1 receptor antagonist (IL-1Ra), to block IL-1's effects in neonatal Klebsiella sepsis in the absence of antibiotic treatment. Newborn Wistar-Kyoto rats were injected intraperitoneally with a single dose (10 mg/kg) of either IL-1Ra (n = 43) or human serum albumin as a control (n = 40). At the same time, a 50% lethal dose of K. pneumoniae was injected subcutaneously. No antibiotics were given at any time. After 10 days, survival was 60% for the albumin group and 80% for the IL-1Ra group (P < 0.01). IL-1Ra treatment also afforded protection when the dose of bacteria was increased sixfold (P < 0.01). There were two episodes of leukopenia in the control group, which were suppressed by IL-1Ra (P < 0.01 and P < 0.001). IL-1 and IL-6 levels were lower in the IL-1Ra-treated group (P < 0.05 and P < 0.001, respectively). No differences between the two groups were observed in the number of bacteria in cultures of the blood, lungs, liver, or spleen. When IL-1Ra (10 mg/kg) was given both at time zero and 24 h after bacterial challenge, lethality was significantly increased (P < 0.01). Single doses of IL-1Ra of from 20 to 40 mg/kg progressively increased lethality compared with controls (P < 0.01) in both Wistar-Kyoto and Sprague-Dawley strain rats. In the same model, low doses of IL-1 itself (0.4 ng per rat), given 24 h prior to bacterial challenge, afforded protection (P < 0.001). These studies suggest that, in the absence of antibiotics, partial blockade of IL-1 receptors improves survival, whereas a longer or greater blockade increases lethality in newborn rats infected with K. pneumoniae. PMID- 8432614 TI - Experimental gastritis induced by Helicobacter pylori in Japanese monkeys. AB - We used Japanese monkeys (Macaca fuscata) to establish an experimental model in order to clarify the pathogenicity of Helicobacter pylori in gastric and duodenal disorders. A suspension (5 ml; 10(9) CFU/ml) of H. pylori cells isolated from humans was sprayed around the antrum of the stomach of each of 12 of 17 animals with an endoscope. The remaining five animals were not inoculated; they served as a control group. On days 7, 14, and 28 after inoculation, the gastric mucosa samples were examined grossly and were biopsied for microscopic examination with an endoscope. H. pylori was recovered from 7 of the 12 inoculated animals (58%), and infiltration by neutrophils and monocytes was observed histologically. Macroscopic gastritis with erythema and erosions were noted for five of these animals. On day 28 after inoculation, five animals in the infected group were treated with ampicillin. In two infected but untreated animals, the bacteria persisted for more than 6 months. The result of the gastritis scoring of the antral mucosa and the ammonia concentration in the gastric secretion were significantly higher (P < 0.01 to 0.001) for the infected group than for the control group; however, these values decreased to levels comparable to those for the control group after treatment with ampicillin. Urease activity was positive in gastric biopsy specimens from five of the seven animals in the infected group after 7 days and from four of these animals after 14 days but was negative in all specimens from animals in the control group. The level of antibody (immunoglobulin G) in serum for the infected group was elevated but changed very little for the control group. These results suggest that this M. fuscata model can be used to study H. pylori infection and that H. pylori can induce gastritis. PMID- 8432615 TI - Cloning and characterization of the Actinobacillus pleuropneumoniae-RTX-toxin III (ApxIII) gene. AB - To study the role of Actinobacillus pleuropneumoniae-RTX-toxin III (ApxIII) in the pathogenesis of porcine pleuropneumonia, we cloned and characterized the gene encoding this toxin. For that purpose, we screened an expression library of genomic DNA of serotype 8 with an ApxIII-specific monoclonal antibody and isolated a 425-bp fragment of an immunoreactive clone. Using this fragment as a probe, we identified and cloned an overlapping chromosomal NsiI restriction fragment of 5.0 kbp. Escherichia coli cells that contained this fragment produced a protein similar to ApxIII. Like ApxIII, the protein had a molecular mass of approximately 120 kDa, was recognized by an ApxIII-specific antibody, killed porcine lung macrophages, and was not lytic for sheep erythrocytes. We concluded from these data that the 5.0-kbp NsiI fragment contained the ApxIII-coding gene. Nucleotide sequence analysis of the 5.0-kbp NsiI fragment revealed the presence of two genes, apxIIIC and apxIIIA. These genes coded for proteins ApxIIIC and ApxIIIA, respectively, which were 53 and 50% identical to the prototypic RTX proteins HlyC and HlyA of E. coli. We assumed that the apxIIIA gene coded for the structural RTX toxin and that the apxIIIC gene coded for its activator. In addition, we found that ApxIII could be secreted from E. coli by the heterologous RTX transporter proteins HlyB and HlyD. The deduced amino acid sequence of ApxIIIA was 50% identical to that of ApxIA and 41% identical to that of ApxIIA. We concluded that, beside ApxI and ApxII, ApxIII is the third RTX toxin produced by A. pleuropneumoniae. PMID- 8432616 TI - Characterization of bovine neutrophil antibacterial polypeptides which bind to Escherichia coli. AB - Bovine neutrophils contain several cationic polypeptides which exert potent microbicidal effects in vitro. To better characterize the repertoire of these polypeptides, we have incubated extracts of bovine neutrophils or neutrophil granules at pH 4 or 7 with either a smooth strain of Escherichia coli or a rough one. Only a few polypeptides interacted with the bacterial surface and were subsequently desorbed with 200 mM MgCl2, as revealed by gel electrophoresis and analysis of Western blots (immunoblots) with appropriate antibodies. Two of the main proteins appearing in Coomassie blue-stained gels have molecular masses of 53 and 15 kDa and correspond to the heavy and light chains of myeloperoxidase. Another prevailing protein band with a molecular mass of 31 kDa was purified and shown to be 87% identical to human azurocidin/CAP37 in its 22-amino-acid N terminal sequence. Proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and blotted to nitrocellulose did not react with an antiserum to human bactericidal/permeability-increasing protein. Conversely, immunoglobulin G against Bac7 or Bac5, two members of the antimicrobial proline- and arginine rich polypeptide family, recognized in Western blots both the inactive precursor molecules, proBac7 and proBac5, and the mature polypeptides. PMID- 8432617 TI - Endogenous and exogenous glucocorticoids have different roles in modulating endotoxin lethality in D-galactosamine-sensitized mice. AB - Endotoxin sensitivity and dexamethasone protection have been assessed in mice that were adrenalectomized and also treated with D-galactosamine at the time of endotoxin challenge. Our data establish that adrenalectomy did not detectably alter the magnitude of the increased sensitivity induced by D-galactosamine alone. Furthermore, protection provided by acute exogenous glucocorticoid treatment was still demonstrable in these mice and was not influenced by chronic experimentally induced glucocorticoid deficiency. Our data confirm that the adrenalectomized mouse model of endotoxin lethality is characterized by increased sensitivity to endotoxin and establish that the magnitude of this sensitizing effect is more than 100-fold. We also show for the first time that adrenalectomy causes an appreciable kinetic shift in the endotoxic crisis and that dexamethasone, given at the time of endotoxin challenge, will significantly reverse the increased sensitivity to lethality. Our results indicate that the protective effects of corticosteroids may involve important chronic as well as acute responses. In particular, we conclude that endogenous glucocorticoid need not always increase host resistance to endotoxin, nor does such a circumstance eliminate the possibility for exogenous glucocorticoid-mediated protective effects. PMID- 8432618 TI - Cloning of the Streptococcus gordonii PK488 gene, encoding an adhesin which mediates coaggregation with Actinomyces naeslundii PK606. AB - Coaggregation between Streptococcus gordonii PK488 and Actinomyces naeslundii PK606 is mediated by a 38-kDa streptococcal protein, designated ScaA. The gene, scaA, which encodes this protein has been cloned into Escherichia coli. A genomic S. gordonii PK488 library (in Lambda ZAP II) was screened with anti-S. gordonii immunoglobulin G absorbed with S. gordonii PK1804, an isogenic coaggregation defective mutant of strain PK488. A positive recombinant phage was isolated, and a phagemid designated pRA1 was obtained which contained a 6.6-kb insert. Expression of scaA from pRA1 and from a subcloned internal 2.1-kb fragment was observed. The absorbed antiserum cross-reacted with a 34.7-kDa protein, SsaB, from S. sanguis 12, also a coaggregation partner of A. naeslundii PK606. Absorbed antiserum to S. gordonii PK488 and antiserum to SsaB both reacted with 38-kDa proteins in supernatants from mildly sonicated preparations from 11 other coaggregation partners of A. naeslundii PK606. Putative adhesin genes were identified in each of these coaggregation partners by Southern analysis of their genomic DNA with the cloned 2.1-kb fragment as a probe. A 30-base oligonucleotide probe based on the sequence of ssaB of S. sanguis 12 hybridized in an identical manner. These data extend the notion that most of the viridans streptococci that coaggregate with actinomyces are capable of expressing ScaA-related proteins. PMID- 8432619 TI - Plasmodium falciparum-specific immunoglobulin G (IgG), IgM, and IgE antibodies in paired maternal-cord sera from east Sepik Province, Papua New Guinea. AB - Enzyme-linked immunosorbent assay (ELISA) and Western blot (immunoblot) serological analyses for immunoglobulin G (IgG), IgM, and IgE antibodies to Plasmodium falciparum were made from 46 maternal-cord serum pairs obtained from parturient East Sepik (Papua New Guinea) women and their newborn. Concurrent study of these women had shown that placental parasitemia rates were related to parity with the highest rate (41%) in the primiparous group and the lowest rate (3%) in the women who had given birth more than three times (> 3 parity group). Overall ELISA positivity rates for antimalarial IgG, IgM, and IgE antibodies in the maternal sera were 54.3, 28.2, and 8.3%, respectively, while those for the cord sera were 36.9, 0, and 16.6% respectively. Seropositivity rates were not related to maternal parity group, except for maternal IgE, in which there was a higher rate, of borderline significance, in the > 3 parity group than in the primiparous group. Cord IgE positivity was largely independent of maternal positivity and vice versa. Cord and maternal IgG immunoblot pairs showed near homology. IgG antibodies to the P. falciparum antigens of sizes < 36 kDa were either weak or absent in parity group 1 and 2 maternal-cord serum pairs. Neither ELISA or immunoblot revealed IgM antibody in the cord serum samples. Maternal IgM antibodies showed a heterogeneity of responses both between paired IgG immunoblots and between different serum samples. The IgE immunoblots exhibited a similar diversity, albeit of less complexity. The presence of P. falciparum specific IgE in the cord sera would indicate that prenatal immune hypersensitization of the fetus to malaria had occurred. PMID- 8432620 TI - PMA inhibits NK cell generation, cytotoxic activity and NK-1.1 expression. AB - We investigated the role of protein kinase C activator phorbol 12-myristate 13 acetate (PMA) on IL-2-driven NK cell differentiation, by using an in vitro model previously set up by our laboratory. Bone marrow precursor cells, from mice treated with 5-fluorouracil (FUBM), when cultured with IL-2, generated mature NK cells. The biochemical system involved in this process has not yet been defined. We investigated the possible mechanism by analyzing the effect of PCK activator PMA on NK cell differentiation and lytic activity of mature NK cells. We now report that: (1) PMA inhibited the IL-2-induced NK cell differentiation and induced development of cells which lyse the NK-resistant target P815. (2) PMA inhibited the lytic ability of mature NK cells against NK-sensitive target YAC-1. We evaluated the effects of PMA using the expression of NK-associated antigen NK 1.1 and the ability to lyse YAC target as parameters of NK cell differentiation. PMA down-regulated both these parameters, reducing their expression during the differentiation process of NK cells and inducing down-modulation of these in mature NK cells. The results suggest that PKC regulatory control could be under the process of differentiation and activation of NK cells. PMID- 8432621 TI - The beta 2-adrenergic agonist terbutaline suppresses acute passive transfer experimental autoimmune myasthenia gravis (EAMG). AB - Treatment of Lewis rats with the beta 2-adrenergic agonist terbutaline suppressed clinical symptoms of acute passive transfer EAMG induced with monoclonal anti acetylcholine receptor antibody and accelerated clinical recovery in affected animals. Electrophysiological studies showed that the amplitude of the first compound muscle action potential was significantly larger in terbutaline-treated rats as compared to controls. In both groups, a comparable number of inflammatory cells at the muscle endplates was seen. PMID- 8432622 TI - Stimulating effect of DEODAN (an oral preparation from Lactobacillus bulgaricus "LB51") on monocytes/macrophages and host resistance to experimental infections. AB - DEODAN is a lysozyme lysate from Lactobacillus bulgaricus for oral administration which has shown antitumor activity in mice and humans. The effects of this preparation on some functions of monocytes/macrophages and on host resistance to experimental infections were examined. The oral administration to mice of DEODAN 150 mg/kg daily (the recommended dose in humans) caused an increase of the spreading ability and phagocytic activity of peritoneal macrophages, which showed morphological signs of cell activation. The level of Interleukin-1 (IL-1) secreted in the culture supernatant of peritoneal macrophages of DEODAN-treated mice was found to be slightly increased only when the mice were treated with 150 mg/kg DEODAN for 10 days. However, the in vitro incubation of human blood monocytes with DEODAN resulted in induction of membrane-bound and cytoplasmic IL 1 and Tumor Necrosis Factor (TNF)-alpha. The oral treatment of mice with DEODAN also caused a decrease in mortality after experimental infections with Klebsiella pneumoniae and Listeria monocytogenes. These results indicate that DEODAN activates the phagocytic and secretory functions of mononuclear cells and increases host resistance to bacterial infections. PMID- 8432623 TI - Aci-reductones enhance interleukin-2-induced lymphocyte cytotoxicity. AB - Arachidonic acid (AA) metabolites and reactive oxygen species (ROS) are implicated in the suppression of interleukin-2 (IL-2) activity. We investigated the effects of aci-reductones, compounds that function both as inhibitors of AA metabolism and as scavengers of ROS, on the generation of IL-2-induced, lymphokine activated killer (LAK) activity. Aci-reductones belonging to the 4 aryl-2-hydroxytetronic acid system improved the in vitro generation of LAK activity from IL-2-treated human peripheral blood mononuclear cells (PBMC) approximately 4-fold. Those aci-reductones belonging to the 3,4 dihydroxyhenzofuranone class were less effective. LAK activity improvement was comparable to that produced by indomethacin with superoxide dismutase plus catalase and comparable to the improvement produced by depleting PBMC of monocytes. Aci-reductones completely suppressed the production of prostaglandin E2 from PBMC in response to IL-2 and partially suppressed superoxide anion production. Daudi cell and lymphocyte subset proliferation and monocyte viability were not affected. Less improvement in LAK activation was observed when PBMC depleted of monocytes were exposed to IL-2 and aci-reductones. We conclude that aci-reductones improve LAK generation from PBMC in vitro. This property may be mediated via effects on monocyte AA and ROS metabolism. PMID- 8432624 TI - Characterization of the inhibition of renal translation in the Sprague-Dawley rat following in vivo cyclosporin A. AB - "Run-off" translation assays in microsomes isolated from Sprague-Dawley rats were used to examine the capacity of cyclosporin A (CsA) to alter translation elongation. CsA added in vitro in concentrations of up to 100 micrograms/ml did not reduce "run-off" translation measured as 3H-L-leucine incorporation in microsomes isolated from the rat kidney or thymus. In contrast, the oral administration of CsA at 50 mg/kg/day for 6 days resulted in reductions in 3H-L leucine incorporation by microsomes isolated from rat kidneys and unstimulated thymus to 21.6 and 83.0% of control values, respectively. In cross-over experiments between renal microsomal and cytoplasmic fractions, 3H-L-leucine incorporation was inhibited following the addition of renal cytoplasm from CsA treated rats to renal microsomal fractions from control vehicle treated rats. Translation inhibition was still observed when renal cytoplasm from CsA treated rats was added along with renal cytoplasm from control rats to renal microsomes isolated from rats treated with control vehicle. Reductions in renal 3H-L-leucine incorporation were not due to a stimulation of renal protease activity. Experiments varying the concentration of individual components of the microsomal translation assays suggested that renal microsomes from CsA treated animals were saturated with substrate or cofactor at lower concentrations than control microsomes. Time course experiments showed a marked reduction in the duration and extent of 3H-L-leucine incorporation by renal microsomes from CsA treated animals compared to controls. Sucrose density gradient analysis of microsomes from CsA treated animals confirmed that elongation was inhibited. These findings suggest that the in vivo administration of CsA results in the formation of a direct acting inhibitor of renal translation rather than reducing translation by producing changes in renal transcription. The observation that renal translation is inhibited only after in vivo CsA suggests that a CsA metabolite formed in, or taken up by, the kidney produces translation inhibition, or that a cellular product involved in translation or translation regulation is formed or induced. We propose that the CsA induced inhibition of renal translation elongation accounts, at least in part, for CsA-induced nephrotoxicity. PMID- 8432625 TI - Cocaine suppresses proliferation of phytohemagglutinin-activated human peripheral blood T-cells. AB - Cocaine has been reported to modulate the immune system of experimental animals. Also, we observed that the drug suppresses the phytohemagglutinin (PHA)-induced proliferation of human peripheral blood mononuclear cells (PBMCs) but at concentrations extremely high relative to those seen in the blood of drug abusers. This suggested that cocaine had a relatively weak effect when tested under conditions of optimum proliferation. We, therefore, decided to examine the effect of lower concentrations of cocaine on suboptimum PHA-induced proliferation. At 0.09-12 microM, cocaine had no effect on the proliferation of PBMC in response to 0.2 micrograms/ml PHA. However, depleting the population of B cells and monocytes resulted in a drug-induced suppression of the residual T cells. Maximum suppression by cocaine was observed at 3 microM with both higher and lower concentrations of the drug causing less suppression. Suppression of proliferation was not influenced by either the age or sex of the peripheral blood lymphocytes (PBL) donors. The suppression of T-cell-enriched PBLs induced by cocaine could be eliminated by increasing the dose of the mitogen but was enhanced by preincubating the cells with the drug for 24 h. Also, the drug suppressed cytosolic free calcium mobilization in Fura 2/AM loaded enriched T cell populations. These results show that cocaine moderately but consistently suppresses PHA-induced proliferation of T-cells from random blood donors at drug concentrations observed in drug abusers. The suppression is only evident under conditions of suboptimum proliferation and is accompanied by a corresponding decrease in the mobilization of cytosolic free calcium. It is suggested that the weak suppressive effect of cocaine is reversed by either helper factors produced by accessory cells or increasing concentrations of mitogen. These factors when present possibly overcome a drug-induced reduction in calcium mobilization and lymphocyte activation. PMID- 8432626 TI - Patients benefit if cancer specialists, family physicians communicate. AB - Cancer patients often have needs the specialist can't fill. This oncologist discusses the special role family physicians can play when their patients are undergoing treatment for cancer. PMID- 8432627 TI - Cancer rates and treatment options both increase for Iowans. PMID- 8432628 TI - Scott County was willing to accept small sacrifice. PMID- 8432629 TI - Primary cancer of the head and neck. AB - One hundred and seventy-eight cases of squamous cell carcinoma of the head and neck were reviewed. The incidence of second malignant neoplasms was 15%. The authors conclude that environmental and life-style factors contributed to the development of a second malignancy. PMID- 8432630 TI - A patient with 56 primary malignancies. AB - This very unusual case involves a 70-year-old white male who was within 50 miles of atomic bomb testing in the Mohave Desert and had 56 primary malignancies from 1946 to 1992. Major cytogenetic abnormalities sometimes found in patients with apparent genetic susceptibility for developing solid tumors are reviewed. PMID- 8432631 TI - When to transfer from acute to skilled. PMID- 8432632 TI - Medical informatics and continuing education. PMID- 8432633 TI - Argyll and Clyde general practitioners' attitudes to standard setting in hypertension. AB - A questionnaire was sent to a one in five sample (68 GPs) of General Practitioners (GPs) in Argyll and Clyde Health Board to determine attitudes to standard setting in hypertension and the response rate was 80.7% (55 GPs). Thirty six GPs (65.4%) stated that they would be interested in sharing care with a consultant who had an interest in the subject and 27 GPs (49.1%) stated that they would be interested in taking part in an educational audit of their hypertensive patients. The results of the study suggest that it would be possible to obtain broad agreement among GPs on standards for diagnosis, treatment and appropriate indications for hospital referral in the management of hypertension but in order to develop consensus further it would be necessary to carry out a more detailed study using a larger cohort of GPs. PMID- 8432634 TI - A busy urban geriatric day hospital: analysis of one year's activity. AB - Lightburn Geriatric Day Hospital is a 30-place unit sited adjacent to Geriatric Assessment and Rehabilitation wards and three miles from the local district general hospital in east Glasgow. The service serves an urban population of 25,000 persons aged 65 or more. During 1991 a data capture form was used to prospectively record Day Hospital referral patterns and activity. There were 731 new patient referrals, accounting for a total of 5,780 patient attendances. Thirty-eight per cent of new patients attended without prior screening (unscreened General Practitioner (GP) referrals). Booked occupancy was 85.5%, actual occupancy 76%. The average period of attendance was three weeks (median number of attendances: 7) and 18% of attenders required in-patient care. Specific after-care arrangements were made for 85% of patients on discharge from day hospital. Low rates for re-attendance (within three months of day hospital discharge) and chronic attendance (more than three months) as well as favourable responses from surveys of both GPs and patients suggest effective use of the Day Hospital resource, but more direct measures of Day Hospital effectiveness are required. PMID- 8432635 TI - Using the Community Health Index, general practitioner records and the National Health Service Central Registry for a 14 year follow-up of a middle-aged cohort in the west of Scotland. AB - Record linkage provides an opportunity for relatively inexpensive follow-up in cohort studies. Most studies have used hospital records. However, the Community Health Index, which is a computer-held list of all patients registered with General Practitioners (GPs), now offers opportunities for measuring morbidity at the primary care level. Searching for patients individually on this computer-held Index, we identified 96% of a middle-aged cohort recruited 14 years earlier in a longitudinal study in the West of Scotland. Of these, information was obtained for 78% through direct postal survey and for 87% through contact with GPs. In total, follow-up information was obtained on 903 (92%) of those thought to be alive. The National Health Service Central Registry records data and cause of death and will pass this information to special studies which have 'flagged' individuals' records. Seven per cent of the deaths in this sample had been missed by this process. This may need to be taken into account in previous studies of mortality for this cohort. New studies could expect successful long-term follow up through record linkage to the Index or the Registry, and automatic record linkage with the Index would be worth investigating. PMID- 8432636 TI - Models of accreditation in health care. AB - Models of accreditation in health care and their origins are briefly described. Current approaches to Quality Management systems used in the United Kingdom are discussed, and a recommendation is made for professional leadership in the independent accreditation of health services. PMID- 8432637 TI - Use of a community-based touch-screen public-access health information system. AB - Meeting the demands of patients and the public for health information is now a recognised aim. Healthpoint is a community-based touch-screen public-access health information system which aims to make health information easily accessible by the public and to provide feedback information on this demand. We have assessed Healthpoint in an experiment in three parts. Part one was a survey of 13 Healthpoints for several weeks in various community sites in Glasgow, such as a shopping centre, supermarket, library, and pub, as well as health service sites such as out-patient department and general practice. The number of users and the topics chosen were recorded by the systems. Part two was a survey of ten Healthpoints in one town (Clydebank) over five months, which examined routine information recorded by the system, and interviews with an opportunistic sample of 300 weekday shoppers in the street and a random sample of 271 by telephone. Part three was a survey of one Healthpoint in a general practice for 36 weeks using routine recording by the system and a postal survey of a systematic sample of 250 attenders. Seventy five (25%) out of 300 in the street survey and 45 (22%) of the telephone sample who had visited a site where there was a Healthpoint had used it. Overall, 17% of the telephone sample had used it. Seventy three (27%) out of 200 general practice attenders had used Healthpoint.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8432638 TI - A review of Fife's food and health policy. AB - Fife Health Board published its food and health policy in May 1986, introduced a board-wide food and health strategy in 1987, and carried out a comprehensive review of its implementation in 1990. Other health boards currently considering their strategies may benefit by learning from Fife's experience. A number of base line studies were carried out between 1987 and 1989 before the policy was implemented. Further surveys have monitored progress. Positive features of the programme included the introduction of a comprehensive food and health policy throughout the health board, the establishment of base-line measurements for future outcome evaluation, and the enthusiastic support of a wide range of people. Negative features included some opposition from a number of health service staff to its introduction, lukewarm support from public leaders for its proposed public launch, and a patchy response from the education sector. Although it is still too early to be confident of the success of policy in terms of outcome measures, there is some evidence that the first phase of its introduction may have had some success within the health service. Alternative strategies are now required to tackle some of the areas where the introduction was less successful. PMID- 8432639 TI - Out of hours emergency dental service provision in Scotland--a survey of Health Boards. AB - Dental practitioners are a source of out of hours emergency dental care, but Health Boards in Scotland have been encouraged to make certain additional provision. A survey carried out in July 1991 has shown that ten of the 15 Scottish Health Boards operate a centralised, out of hours emergency dental service. The areas without such a service are mainly rural and with a small population, where setting up a scheme would be expensive and difficult. Only one Health Board operates a weekday service, but all of the Boards which provide a service operate it at weekends and on public holidays. There is considerable variation in the extent and use of the services provided by the different health boards. The greatest use of emergency dental services is in areas where the dentist:population ratio is good. PMID- 8432640 TI - Voluntary agency support for people with mental health problems: a survey of consumer attitudes. PMID- 8432641 TI - Survey of four day care facilities at the Royal Edinburgh Hospital. AB - A survey is described which compared patients' rehabilitation status, activities, needs and reasons for attending at four different psychiatric day care units attached to one hospital. The views of staff and patients were also examined. PMID- 8432642 TI - Public reaction to radiation: fear, anxiety, or phobia? AB - Public fear reactions to ionizing radiation are discussed in a social psychological context. The common use of the terms fear, anxiety, panic, and phobia is related to their clinical meanings, and the authors stress the importance of caution when using certain psychiatric terms for interpreting public reactions to radiation. Differences related to existing knowledge and belief structures, trust, and preferences, create obstacles to effective communication; however, the study of such differences also offers explanations to different reactions and different viewpoints. More information and communication on radiation, clear behavioral guidelines in situations of increased radiation levels, and respect for citizens' concerns about radiation protection would counterbalance lay people's fears and feelings of vulnerability. Such measures may enhance familiarity with radiation, increase perceived personal control in anxiety-creating situations, and develop trust in authorities and their expertise. PMID- 8432643 TI - ECOSYS-87: a dynamic model for assessing radiological consequences of nuclear accidents. AB - The time-dependent radioecological simulation model ECOSYS-87 has been developed to assess the radiological consequences of short-term depositions of radionuclides. Internal exposure via inhalation and ingestion, as well as external exposure from the passing cloud and from radioactivity deposited on the ground, are included in the model. The site-specific parameter values of the model are representative of Southern German agricultural conditions; however, the model design facilitates adaption to other situations. The ingestion dose is calculated as a function of time considering 18 plant species, 11 animal food products, and 18 processed products. The ingestion and inhalation exposure is estimated for six age groups using age-dependent consumption and inhalation rates and age-dependent dose factors. Results demonstrate a pronounced influence regarding the time of year (season) of deposition on the ingestion dose and on the relative importance of the exposure pathways. Model results compare well with activities in foods measured after the Chernobyl accident. PMID- 8432644 TI - Skeletal 210Pb levels and lung cancer among radon-exposed tin miners in southern China. AB - A preliminary case-control study of 19 lung cancer cases older than 55 y and 141 age-matched controls was carried out among a group of underground miners in Southern China who were exposed to 222Rn and its decay products. 210Pb activity levels were measured in the skull to estimate radon exposure. Radon exposure was also estimated in working level months, based on work histories and available industrial hygiene data. There was a smooth gradient of lung cancer risk with categories of skeletal 210Pb level at time of last radon exposure; relative risks of 1.0, 2.9, 3.2, and 4.7 for categories < 51.8, 51.8-77.7, 77.8-107.3, and > or = 107.4 Bq (< 1,400, 1,400-2,099, 2,100-2,899, and > or = 2,900 pCi), respectively. Relative risks were unaffected by adjustment for exposure to arsenic in the mine or by adjustment for working level months. Risks also increased with cumulative working level month exposure, but the gradient of risk lessened after adjustment for exposure to arsenic. 210Pb, at the time of last radon exposure (p = 0.13) and at the current 210Pb level (p = 0.01), was not highly correlated with the working level month estimate. Data were sparse but smoking had minimal effect on risk gradient with level of skeletal 210Pb activity. This study suggests measured 210Pb level may be a more precise predictor of lung cancer risk than working level month. PMID- 8432645 TI - An elementary method for implementing complex biokinetic models. AB - Recent efforts to incorporate greater anatomical and physiological realism into biokinetic models have resulted in many cases in mathematically complex formulations that limit routine application of the models. This paper describes an elementary, computer-efficient technique for implementing complex compartmental models, with attention focused primarily on biokinetic models involving time-dependent transfer rates and recycling. The technique applies, in particular, to the physiologically based, age-specific biokinetic models recommended in Publication No. 56 of the International Commission on Radiological Protection, Age-Dependent Doses to Members of the Public from Intake of Radionuclides. PMID- 8432646 TI - Calculated stopping powers of low-energy electrons in some materials of interest in radiation protection. AB - Stopping powers of low-energy (< 10 keV) electrons in aluminum, copper, cesium, barium, lead, lithium, and uranium were calculated using an analytic method. The interaction of the electrons with the materials were characterized in terms of three cross sections for total ionization and total scattering. Experimental cross section data were collated, where available, for the materials. The expressions were then fitted to the data to obtain the values of the relevant constants in the expressions. This enabled the basic equation of stopping powers of electrons to be evaluated for the materials. Comparison of the results obtained with those of other workers was affected. PMID- 8432647 TI - Statistical uncertainties associated with multiplexed sampling with a continuous radon monitor. AB - One common type of continuous radon monitor is a flow-through device that counts alpha emissions from a gas sample as it passes through a scintillation cell. To improve the ability of this type of continuous radon monitor to track time varying radon concentrations, a forward-marching data analysis procedure that considers the production, deposition, and decay of radon progeny as a function of time had been previously developed. This paper examines some of the statistical issues associated with using such a monitor and applying the forward-marching analysis procedure to the problem of multiplexed radon concentration samples. It uses Monte Carlo simulations, together with limited experimental data, to perform: 1) an examination of the potential bias of the forward-marching analysis technique; 2) an examination of a simplified methodology for evaluating concentration-measurement uncertainty for various radon concentration histories; and 3) an analysis of an example application of the simplified uncertainty analysis to multiplexing of soil-gas samples. The results of these analyses indicate: 1) that the forward-marching analysis technique is relatively unbiased, at least at concentrations > 148 Bq m-3 for time steps longer than 120 s; 2) that a simplified uncertainty analysis procedure based upon Poisson statistics and no error correlation between intervals provides generally acceptable estimates of measurement uncertainty; and 3) that such a monitor and analysis technique can be successfully employed to measure multiplexed soil-gas samples, but is not appropriate for multiplexing of most building concentrations. PMID- 8432648 TI - Radium needle used to calibrate germanium gamma-ray detector. AB - A standard platinum-iridium needle that contains 374 MBq 226Ra was tested as a source for calibrating a portable germanium detector used with a gamma-ray spectrometer for environmental radioactivity measurements. The counting efficiencies of the 11 most intense gamma rays emitted by 226Ra and its short lived radioactive progeny at energies between 186 and 2,448 keV were determined, at the full energy peaks, to construct a curve of counting efficiency vs. energy. The curve was compared to another curve between 43 and 1,596 keV obtained with a NIST mixed-radionuclide standard. It was also compared to the results of a Monte Carlo simulation. The 226Ra source results were consistent with the NIST standard between 248 and 1,596 keV. The Monte Carlo simulation gave a curve parallel to the curve for the combined radium and NIST standard data between 250 and 2,000 keV, but at higher efficiency. PMID- 8432649 TI - Measuring additional dose rate contributed by nuclear plants. AB - Monitoring systems have been constructed to measure the net additional dose rate contributed by a nuclear plant. These systems compensate for the higher dose rate due to an increase in the natural background during rainfall or from formation of an inversion layer. The systems are simple, consisting of only four instruments; a NaI detector, a dose-rate-conversion unit to convert the distribution of pulse heights to dose rate, and two single-channel analyzers. These systems, called NaITSCA systems, have three outputs: one dose rate and two counting rates. These outputs are used to judge if the dose rate increase is due to a nuclear plant and to estimate the net additional dose rate. The Fukui Prefecture Environmental Radiation Remote Monitoring Systems are equipped with these instruments. These systems provide information every 10 min. The detection limit sensitivity of the net additional dose rate is about 5 nGy h-1. PMID- 8432650 TI - Measurement of activity in anthropomorphic organ phantoms. AB - This paper describes two nondestructive measurement techniques for determining the radioactivity in a homogeneous organ phantom with an acceptable error and the capability of being traceable to the National Institute of Standards and Technology. These two techniques are based on a method developed by Robley D. Evans in 1937 for measuring the amount of radium deposited in a living person. There are two significant improvements in the new techniques: 1) the radially dependent error is eliminated, and 2) the effect of self absorption in the unknown body is measured and taken into account. The first assay method is a single-source technique involving four measurements and requiring only one standard source, the second one is a double-source technique involving six measurements and requiring two unequal standard sources. Three pairs of lung phantoms radiolabeled with 241Am, 137Cs, and 154Eu were measured with both the single- and double-source techniques. The results imply that the self-attenuation of photons within the organ phantom cannot be neglected, especially at low energies. Finally, potential applications (other than the calibration of bioassay phantoms of the single- and double-source techniques) and their limitations are discussed. PMID- 8432651 TI - Lethal acute whole-body dose and civil defense. PMID- 8432653 TI - Health physics curriculums. PMID- 8432652 TI - Should ICRP have prescribed an averaging period for the occupational dose limit in its basic general recommendations? PMID- 8432654 TI - Role of the conventional analytical methods in the variation of reported uranium concentrations. PMID- 8432655 TI - 201Tl concentration in breast milk. PMID- 8432656 TI - A note on certain inconsistencies in ICRP-60. PMID- 8432658 TI - Generalized source term for the multiphase radon transport equation. PMID- 8432657 TI - Chalk River beta quartz fiber electroscope. PMID- 8432659 TI - Experimental host-induced selection in Schistosoma mansoni strains from Guadeloupe and comparison with natural observations. AB - Allelic frequency variation at the malate dehydrogenase (E.C.1.1.1.37) polymorphic locus (Mdh-1) was analysed during several successive generations in four strains of Schistosoma mansoni from Guadeloupe, maintained experimentally on mice. A rapid evolution of the frequency of the Mdh-1a allele is interpreted as being the result of an interaction between experimental drift and selection induced by the murine laboratory host. These experimental results are compared to the genetic structures observed among the corresponding natural populations of S. mansoni in Guadeloupe (West Indies). They strengthen the hypothesis of a natural host-induced selection by the murine host (Rattus rattus), which, in Guadeloupe, plays the role of host reservoir for this human schistosome. PMID- 8432660 TI - The effect of periodic bottlenecks on the competitive ability of Drosophila pseudoobscura lines. AB - Competition experiments between several Drosophila pseudoobscura strains that were previously subjected to periodic bottlenecks of different sizes and D. willistoni have been carried out. Contrary to previous results with these two species, where stable coexistence was detected, populations of D. pseudoobscura displaced D. willistoni in a few generations. By using a relative fitness measure, the control lines (that had not gone through bottlenecks) outcompeted D. willistoni faster than bottlenecked lines. One of these, corresponding to the minimum possible bottleneck size of one pair, also shows significantly lower relative fitness than the other strains. These results are discussed in relation to the effect of periodic bottlenecks in reducing genetic variability and its incidence on the competitive ability of these lines. PMID- 8432661 TI - Selective screen to recover pairs of deletion-tandem duplications. AB - A method of selecting pairs of deletion-tandem duplications in an autosome arm of Drosophila has been developed. Males containing autosome 2 and the right and left free arms of this autosome produce gametes with the metacentric and the free arm through meiotic non-disjunction. Unequal exchanges induced in such gametes give deletions and tandem duplications within the left or right chromosomal arms. This approach removes the necessity of using markers to identify deletions in the chromosome region. PMID- 8432662 TI - Analysis of cell ploidy in histological sections of mouse tissues by DNA-DNA in situ hybridization with digoxigenin-labelled probes. AB - DNA-DNA in situ hybridization, with two digoxigenin-labelled, chromosome-specific DNA probes, was used to determine the number of copies of a given chromosome in interphase nuclei and so identify putatively polyploid nuclei in histological sections of several mouse tissues. One hybridization site per diploid genome was expected for tissues with hemizygous markers: male mice hybridized with a Y chromosome probe (pY353/B) or hemizygous transgenic mice hybridized with a beta globin probe (pM beta delta 2). Nuclei with more than one hybridization site were considered putative polyploids. Three groups of experiments were undertaken: (1) evaluation of the method, using mouse liver sections; (2) studies of tissues already known to contain polyploid nuclei, and (3) studies that resulted in the discovery that the mouse ovary contains polyploid nuclei. First, control studies showed that the ability to detect the target DNA sequences was affected by section thickness. Studies of nuclear ploidy in the developing mouse liver revealed a pattern similar to that established by previous studies using DNA content as a criterion for ploidy. At birth, only about 5% of the liver nuclei were polyploid; this increased to 10-15% by 10-20 days and was followed by a sharp increase in the frequency of tetraploid nuclei between 20 and 40 days (to about 35%) and a more gradual increase in higher order polyploid nuclei. Secondly, this technique was used to confirm that polyploid (mostly tetraploid) nuclei were present in the bladder epithelium, heart, uterine decidua and placental trophoblast. Higher order polyploidy was seen in large bone marrow cells (megakaryocytes) but not in the even larger trophoblast giant cells of the placenta, thus confirming previous claims that these cells are polytene rather than polyploid. Thirdly, putatively tetraploid nuclei were found in the ovarian follicle and corpus luteum. As far as we are aware, this is the first time polyploid nuclei have been reported for the mouse ovary. PMID- 8432663 TI - Histochemical localization of oxidized glutathione-catalysing enzymes in human term placenta. AB - This paper reports a new cytochemical affinity technique for detecting oxidized glutathione-binding enzymes by light microscopy and for carrying out fine structural analyses by means of oxidized glutathione labelled with colloidal gold. Albumin-colloidal gold particles were prepared. Oxidized glutathione, added to the solution, replaced albumin on the surface of the gold, thus forming a new histochemical reagent. In human placenta, oxidized-glutathione-catalysing activity was detected on the brush border of the placental villi, over the foldings of endothelial membranes, and in the ground substance of connective tissue in the villous core. Every process of the cell membrane demonstrated enhanced oxidized-glutathione-catalysing activity. This new reagent is a unique example of a low-molecular-weight compound labelled with colloidal gold, and it permits direct measurement of oxidized-glutathione-binding activity in tissue sections. PMID- 8432664 TI - In situ detection of human Ig light-chain mRNA on formalin-fixed and paraffin embedded tissue sections using digoxigenin-labelled RNA probes. AB - Digoxigenin-labelled RNA probes complementary to human immunoglobulin (Ig) kappa and lambda light-chain mRNAs were produced by in vitro transcription. Using these probes, several existing in situ hybridization protocols were studied. By modifying and optimizing pretreatment procedures, which include hybridization, stringency washings and probe detection, a simplified non-radioactive in situ hybridization method for Ig light-chain mRNAs was developed. The light-chain signals were consistently identified in plasma cells, germinal centrocytes, centroblasts and immunoblasts in formalin-fixed and paraffin-embedded sections of lymphoid tissues. Monotypic light-chain mRNA was demonstrated in archival cases of kappa or lambda light-chain-restricted B-cell lymphoma. Background staining was found to be negligible in all the tissues tested. These results indicate that the in situ hybridization methodology described in this study is specific and sensitive for the detection of Ig light-chain mRNAs and has practical value in routine histology. PMID- 8432665 TI - Thiamine pyrophosphatase activity in secretory cells of the lateral prostate and seminal vesicle of normal and castrated guinea pigs and castrates treated with oestradiol. AB - Ultrastructural localization of thiamine pyrophosphatase (TPPase) activity was studied in secretory cells of the lateral prostate and seminal vesicle of normal and castrated guinea pigs and castrates treated with 17 beta-oestradiol benzoate. The present study has demonstrated that TPPase reaction product is consistently localized in the three to four trans cisternae of Golgi complexes in both the lateral prostate and the seminal vesicle. The reaction was intense and the reaction product often filled the cisternae completely. After castration there was a decrease in TPPase activity in both glands as revealed by the reduction in the amount of the reaction product which was found mainly in one to two trans cisternae of the regressed Golgi complex. The reaction product changed from a dense to a more particulate or granular pattern or to discrete deposits of high electron-density. Administration of 17 beta-oestradiol benzoate to the castrates caused changes in the localization and patterns of distribution of TPPase. In the lateral prostate there was an apparent increase in TPPase activity. The reaction product was found in two to four trans cisternae and occasionally in the trans most cisternae of the dilated Golgi complex. The reaction product appeared as discrete, dense coarse precipitates. In the seminal vesicle TPPase reaction product was consistently found in one to two trans cisternae in cells with larger Golgi complexes. However, almost all cisternae of the smaller Golgi complexes were TPPase-positive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8432666 TI - A quantitative histochemical procedure for the demonstration of purine nucleoside phosphorylase activity in rat and human liver using Tetranitro BT and xanthine oxidase as auxiliary enzyme. AB - A quantitative histochemical procedure was developed for the demonstration of purine nucleoside phosphorylase in rat liver using unfixed cryostat sections and the auxiliary enzyme xanthine oxidase. The optimum incubation medium contained 18% (w/v) poly(vinyl alcohol), 100 mM phosphate buffer, pH 8.0, 0.5 mM inosine, 0.47 mM methoxyphenazine methosulphate and 1 mM Tetranitro BT. An enzyme film consisting of xanthine oxidase was brought onto the object slides before the section wa allowed to adhere. The specificity of the reaction was proven by the low amount of final reaction product generated when incubating in the absence of inosine. Moreover, 1 mM p-chloromercuribenzoic acid, a non-specific inhibitor of purine nucleoside phosphorylase, inhibited the specific reaction by 90%. The specific reaction defined as the test reaction, in the presence of substrate, minus the control reaction, in the absence of substrate was linear with incubation time at least up to 30 min as measured cytophotometrically. A high activity was observed in endothelial cells and Kupffer cells of rat liver and a lower activity in liver parenchymal cells. Pericentral hepatocytes showed an activity higher than that of periportal hepatocytes. In human liver, purine nucleoside phosphorylase activity was also high in endothelial cells and Kupffer cells, but the activity in liver parenchymal cells was only slightly lower than it was in non-parenchymal cells. The localization of the enzyme is in agreement with earlier ultrastructural findings using fixed liver tissue and the lead salt procedure. PMID- 8432667 TI - Cell therapy is being tested in the fight against the acquired immunodeficiency syndrome. PMID- 8432668 TI - Progress in scientifically proving the benefits of OMT in treating symptoms of dysmenorrhea. PMID- 8432669 TI - Efficacy of high-velocity low-amplitude manipulative technique in subjects with low-back pain during menstrual cramping. AB - Previous studies have shown that dysmenorrhea produces low-back pain and an electromyographic (EMG) pattern typical of trauma-induced low-back pain. To determine the effects of high-velocity low-amplitude osteopathic manipulative treatment (OMT) on this type of low-back pain, 12 dysmenorrheic subjects were assigned to a group receiving OMT or to a group not receiving OMT (or both). Eight subjects participated in both groups, the other four being equally distributed between groups. Osteopathic manipulative treatment significantly decreased EMG activity during extension of the lumbar spinae erector muscles and abolished the spontaneous EMG activity. These EMG changes coincided with the patient's report of alleviated low-back pain and menstrual cramping. Osteopathic manipulative treatment did not change the creatinine kinase, lactate dehydrogenase or lactate-dehydrogenase isoenzyme activity, or myoglobin concentration. PMID- 8432670 TI - Skin manifestations of human immunodeficiency virus (HIV): Part 2. Noninfectious skin manifestations. AB - The incidence of the acquired immunodeficiency syndrome (AIDS) is rising at an alarming rate. Usually, the first clue that a patient has human immunodeficiency (HIV) infection is the emergence of a skin disease. Early diagnosis and aggressive therapy are vital in the management of these conditions. In Part 1 of this article, the author discussed AIDS-related infectious diseases of the skin. In Part 2, he discusses noninfectious inflammatory diseases, malignant cutaneous neoplasms, and nonclassified skin changes found in HIV-infected individuals, as well as their optimal management. PMID- 8432671 TI - Clinical teaching in the ambulatory care setting: how to capture the teachable moment. AB - As more instruction takes place in an outpatient setting, clinicians must become adept at teaching in this ambulatory care setting. This article suggests ways in which instructors can "seize the moment" by taking advantage of learning opportunities inherent in such an environment. PMID- 8432672 TI - Rheumatoid arthritis, relapsing polychondritis, and pyoderma gangrenosum evolving into non-Hodgkin's lymphoma. AB - In human beings, the function of the immune system and of inflammation is to protect the individual against invading organisms such as bacteria, viruses, parasites, and fungi as well as thermal and mechanical injuries. The inflammatory process, initiated to destroy foreign organisms or an inappropriate immune response/target tissue, may lead to injury, the destruction of host tissue, and the development of the disease process. This article describes the history of a patient with four disorders of unknown cause, all of which may have evolved from one immunologic aberration. PMID- 8432673 TI - Delayed splenic rupture: an unusual cause of the acute surgical abdomen. AB - The diagnosis of delayed rupture of the spleen may be difficult to make because of the presumed triviality of the precipitating injury, an unpredictable time lag between the injury and the development of symptoms, and the possibility of atypical signs and symptoms remote from the bleeding spleen. The clinician may confuse the signs and symptoms with those of acute appendicitis or with some other cause. The authors present two case histories to illustrate the diagnostic difficulties caused by delayed rupture of the spleen. Whenever the acute surgical abdomen is present with concomitant anemia, the diagnosis of delayed rupture of the spleen should be considered. PMID- 8432674 TI - Malignant lymphoma of the maxillary sinus. AB - Cancer of the paranasal sinuses and nasal cavity is an uncommon disease accounting for less than 0.2% of all malignancies. Lymphoma of the paranasal sinuses is a rare clinical entity representing less than 100 cases a year. In most cases, tumors arising in the paranasal sinuses are of the non-Hodgkin's variety. Most of these tumors are asymptomatic in the early stages and are diagnosed only after invasion of adjacent structures with local bone destruction. Computed tomography is essential for staging. The prognosis and treatment of lymphoma of the paranasal sinuses are based on the anatomic staging and histologic subtype. The prognosis is favorable for patients with localized disease. The authors describe a malignant lymphoma of the maxillary sinus in a 44 year-old man. PMID- 8432675 TI - Evoked potentials in neurotoxicology. PMID- 8432676 TI - Effects of occupational exposure to mercury and lead on brainstem auditory evoked potentials. AB - A study was performed to examine the effects of industrial exposures to lead and mercury on the brainstem auditory pathway by recording brainstem auditory evoked potentials (BAEPs). BAEPs were recorded from 22 workers exposed to lead, from eight exposed to mercury and from two control groups of age- and sex-matched subjects never exposed to neurotoxic substances. The time between BAEP peaks I and V were evaluated. The mean durations of exposure were 9.3 and 11.7 years for lead and mercury, respectively. Blood lead concentration (PbBc) on the morning of the test day was 47.5 micrograms/dl, whereas urinary mercury content at the end of the previous work day was 325 micrograms/g creatinine. Both mercury and lead exposed workers showed a significant prolongation of wave I-V time. In addition, the interwave time was longer in a lead subgroup with the greatest mean level of lead in blood. These results are consistent with other studies and show that BAEPs may provide a sensitive tool for detecting subclinical central neurotoxicity caused by lead and mercury. PMID- 8432677 TI - Acute effects of ethanol on pattern reversal and flash-evoked potentials in rats and the relationship to body temperature. AB - The effects of acute ethanol treatment on flash and pattern reversal visual evoked potentials (FEPs and PREPs, respectively) were examined in three experiments using Long-Evans rats. The relationships of evoked potential parameters with blood ethanol concentration and body temperature were examined. In Experiment 1, rats were treated i.p. with vehicle or 0.5, 1.0 or 2.0 g ethanol/kg body weight, and tested 30 min later. The 2.0 g/kg group had prolonged latencies of PREP peaks, no changes in PREP peak-to-peak amplitudes, and lower body temperatures than saline-treated controls. The peak latency shifts were significantly correlated with both blood ethanol concentration and body temperature, and were of a magnitude to be expected from similar changes in body temperature alone. Experiment 2 measured both PREPs and paired-flash FEPs in rats 30 min after injection of either 0, 0.5 or 2.0 g/kg ethanol. PREP changes were found following treatment with the high dose which were similar to those of Experiment 1. Some FEP peak latencies were prolonged and peak-to-peak amplitudes were reduced by both doses of ethanol, despite the fact that body temperatures were reduced at only the high dose. At 2.0 g/kg ethanol, the FEP changes in latency, but not amplitude, were in accordance with what would be expected from body temperature changes alone. The third study attempted to investigate the role of reduced body temperature in producing the visual evoked potential changes by testing at room temperatures of 22 or 30 degrees C. Contrary to expectations, the rats receiving 2 g/kg ethanol were approx. 1 degree C cooler than controls at both room temperatures. Evoked potential latencies were greater in ethanol treated rats than controls at both room temperatures. There were no significant effects of ethanol on FEP amplitudes. Overall, the effects of low doses of ethanol were independent of temperature changes, but the effects of higher doses of ethanol (2.0 g/kg) could not be distinguished from those produced by differences in body temperature alone. PMID- 8432678 TI - Sensory-evoked potentials as indices of neurotoxicity in the rat: effect of 4 tert-butyltoluene. AB - The use of evoked potentials to measure neurotoxicity was evaluated using 4-tert butyltoluene (TBT) as a test compound. Male Wistar rats were habituated to the recordings of auditory- and flash-evoked potentials until the combined waveform of the evoked potentials reached a steady state. The rats were then divided into three groups and exposed to 0, 50 and 150 ppm TBT for 6 h, and the auditory- and flash-evoked potentials were measured for up to 288 h after exposure. Event related potentials specifically associated with the temporal pairing of auditory and visual stimuli were not apparent in the recordings. The peak-to-peak values of selected components, integrated amplitude and power spectra of the waveforms in exposed rats were significantly different from control values for at least 288 h in the group exposed to 150 ppm TBT and for 120 h in the group exposed to 50 ppm TBT. It is concluded that evoked potentials may be used for detection and characterization of minor neurofunctional changes due to low-dose exposure to chemicals. PMID- 8432679 TI - Combined effects of solvents on the rat's auditory system: styrene and trichloroethylene. AB - Because exposures to toxic agents typically involve more than one substance, it is necessary to know if combined exposures pose different risks than those to single agents. Many solvents have been implicated in central nervous disorders and some of them are known to produce hearing loss, probably mediated by damage to cochlear hair cells. Hearing loss was studied by recording the brainstem auditory evoked response (BAER) in male Long Evans rats exposed 8 h/day for 5 days to mixtures of styrene (STY) and trichloroethylene (TCE). Dose groups included air or solvent pairs (STY/TCE) in the following concentrations (ppm): (0:3000), (250:2250), (500:1500), (750:750) and (1000:0). Decreased BAER amplitude, indicative of hearing loss, was correlated with blood levels of total solvent. The effects were as predicted by a linear dose-addition model, indicating neither synergistic nor antagonistic interactions at the concentrations studied. PMID- 8432680 TI - Neurotoxicity screening methods are sensitive to experimental history. AB - Toxicity studies commonly include unavoidable environmental differences (experimental history) among test groups, such as chemical taste, odor and irritation. The influence of environmental variables on USEPA guideline neurotoxicity tests was evaluated using an environmental enrichment model. 6-week old male Fischer 344 rats were housed for 13 weeks in pairs with access to an exercise wheel, trained to run on a rotating rod and handled frequently. Control animals were housed singly, lacked the exercise wheel and rotating rod training, and had only routine interaction with caretakers. At the end of 13 weeks, flash evoked potentials (FEPs), somatosensory evoked potentials (SEPs), auditory brainstem responses (ABRs), grip performance, motor activity (MA), elements of the functional observational battery (activity and reactivity to handling/restraint) and brain histopathology with glial fibrillary acidic protein immunohistochemistry (GFAP IHC) were evaluated. Animals from the enriched group demonstrated changes (P < 0.05) in FEPs, SEPs and grip performance. Enriched animals were more active and reactive to their surroundings, and were highly reactive to physical restraint. Control (unenriched) animals showed little to no exploratory behavior and were more tolerant of restraint. Differences in experimental history can be detected using elements of standard guideline tests and may confound interpretation of such data if not taken into consideration. PMID- 8432681 TI - Effect of intertrial intervals on recovery and amplitude of electrodermal reactions. AB - Convincing findings have been published about the importance of prior activity on electrodermal recovery. However, these studies mainly used tone tasks as an experimental paradigm. The present research investigated the influence of prior activity by changing the intertrial intervals (ITI) in cognitive and reaction time tasks. Results indicated that ITI had no effect on amplitude but had a significant effect on recovery time, a longer ITI period producing a longer recovery curve. No correlation was found between recovery and amplitude. Analysis also indicated that variable intervals should not be recommended between the tasks. These observations emphasize the importance of prior activity on electrodermal recovery in more complex tasks. PMID- 8432682 TI - Laboratory reactivity assessment: effects of casual blood pressure status and choice of task difficulty. AB - In a study of 60 healthy young men, 26 with high and 34 with normal casual systolic pressure, blood pressure and its underlying hemodynamic determinants were measured at rest and during exposure to a series of laboratory tasks. Subjects were given a choice of performing either a difficult or an easy version of a mental arithmetic task, and then offered a similar choice of an easy or difficult stimulated public speaking task. All subjects were given the same tasks, regardless of choice, but led to believe the tasks were the ones they had chosen. During all tasks, subjects with high casual systolic pressure showed greater blood pressure, cardiac output, heart rate and myocardial contractility increases than subjects with normal casual pressure. Within the high casual pressure group, subjects who chose difficult for the mental arithmetic task exhibited greater increases in systolic pressure and heart rate during that task than subjects who chose easy. This subgroup maintained their greater responses during a subsequent mental arithmetic task in which all subjects were told that the difficulty level was the reverse of what they had initially chosen. Choosing difficult on the speaking task was associated with greater increases in cardiac output during performance on that task. Differences in cardiovascular responses associated with choice of difficulty were not evident during performance on tasks which did not pertain to the choice. For mental arithmetic, choice of difficulty was also associated with the psychological trait, fear of failure. These findings are relevant to the development of cardiovascular reactivity assessment procedures, which should attempt to detect psychological as well as physiological determinants of individual differences. PMID- 8432683 TI - Working with psychotic patients. AB - I have discussed a model of the psyche comprising two different modes of thinking, one non-psychotic and the other psychotic. I have related these modes of thinking to our modern myth of Jekyll and Hyde, the study of which could in my opinion give us some insight into their nature. In my view a non-psychotic state of mind belongs to a person who has a history, with particular parents, a particular development, particular conflicts, and operates in the depressive position. A psychotic state of mind belongs to a person who lives in a still and timeless present, with no origin, no development and no conflict, and operates in the paranoid-schizoid position. On the basis of this model I have subsequently described the life history of a psychotic patient and an analytic session in detail, showing how psychotic and non-psychotic states alternate and interact with each other within the same individual and between patient and therapist. The use of my countertransference, moving from a concrete to a symbolic position, has enabled me to make an interpretation. The result of this interpretation has been double, leading to a negative therapeutic reaction. An upsurge of psychotic fury was followed by increased patient/therapist communication, with a small movement from the paranoid-schizoid to the depressive position. PMID- 8432684 TI - Borderline states. Incest and adolescence. PMID- 8432685 TI - Borderline states: disorders of the self. PMID- 8432686 TI - Localization of the GM1 ganglioside in the vestibular system using cholera toxin. AB - Cholera toxin is an ubiquitous activator of intracellular adenylate cyclase and is divided in two major components: A and B. The B-component consists of several subunits that specifically bind to the external cell membrane. The receptor for the toxin, the GM1 ganglioside, is concentrated in nervous tissues. The B subunit of the cholera toxin, conjugated to different molecules (i.e., choleragenoid) is therefore a sensitive anatomical tracer and has been used to detect the presence of GM1 in mammalian tissues. Using choleragenoid, unlabeled and labeled with FITC, we have determined the distribution of the GM1 ganglioside in the vestibular system of the chinchilla. Vestibular tissues were fixed in 4% paraformaldehyde in phosphate buffer, decalcified in 10% EDTA and prepared as either whole-mount, surface-preparations, or for radial cryosections. Positive control tissue consisted of binding to normal brain tissues. Negative controls consisted of several treatments: masking of the GM1 receptors with unlabeled choleragenoid, tissue extraction of GM1 using ethanol, and preabsorbing the choleragenoid with bovine GM1. In addition, to exclude staining of glycoproteins that may have a carbohydrate structure similar to GM1, tissues were digested with trypsin prior to choleragenoid exposure. In the vestibular system, a strongly positive reaction was observed in: the sensory stereocilia and supporting cells of the maculae and cristae, epithelial cells of the planum semilunatum, and polygonal cells of the semicircular canal. Positive but less strong reactivity was observed in the sensory cell body of maculae and cristae, nerve fibers, epithelial cells of utricle and ampulla walls and flattened epithelial cells of the semicircular canals. No reactivity was present in the supporting connective tissue cells and fibrils, blood vessels, gelatinous cupula of the cristae ampullaris and statoconial membranes. Brain tissue showed strong choleragenoid reactivity. The negative controls showed no or greatly reduced reactivity to choleragenoid. Trypsin digestion did not decrease reactivity to choleragenoid. PMID- 8432687 TI - Damage and regeneration of hair cell ciliary bundles in a fish ear following treatment with gentamicin. AB - Sensory hair cells in the striolar regions of the utricle and lagena of a teleost fish, the oscar (Astronotus ocellatus), were damaged following intramuscular injections of gentamicin sulfate. In order to determine whether fish can regenerate hair cells, the time course of damage and recovery was followed over a period of four weeks by scanning electron microscopy. Maximum loss of ciliary bundles occurred at about day 10 after the first of four daily injections of gentamicin (20 mg/kg) in 4-6 cm long fish. The striolar regions were almost totally denuded of ciliary bundles, and there was evidence of considerable hair cell loss. The time course for damage was longer in larger fish, but the recovery of the ciliary bundles appeared to be complete about 10 days after maximal damage was seen in both the smaller and larger fish. These data indicate that Astronotus is able to repair damage to hair cells for an extended period of time post embryonically. PMID- 8432688 TI - Structural variability of the sub-surface cisternae in intact, isolated outer hair cells shown by fluorescent labelling of intracellular membranes and freeze fracture. AB - The intracellular membrane systems in intact, isolated outer hair cells were visualised using the fluorescent membrane probe 3,3'-dihexyloxacarbocyanine iodide (DiOC6) and by freeze-fracture, and f-actin distribution was examined with rhodamine-phalloidin. DiOC6 stained the sub-surface cisternal membranes in the lateral wall and revealed a membrane system running in the centre of the cell from the nucleus to the sub-cuticular region. In optical sections of the lateral wall of fluorescently labelled cells, obtained by scanning laser confocal microscopy, the sub-surface membrane appeared as a fenestrated sheet or a fine network of tubules. Freeze-fracture replicas of rapidly-frozen, unfixed outer hair cells also showed the sub-surface membrane as a fenestrated sheet in some cells or as a network of tubules in others. These combined studies indicate that the interruptions within the cisternal membranes as seen in normal thin sections of outer hair cells are not fixation artefacts but may reflect the dynamic and plastic properties of this membrane system. Double staining of cells with rhodamine-phalloidin and DiOC6 showed substantial co-localisation of intracellular membranes and f-actin. The results suggest there may be a continuous, dynamic endoplasmic reticulum system, forming a core in the centre of the cell, broadening in the subcuticular region and extending down the lateral wall, that may have a role in the turnover and distribution of cytoskeletal assemblies within the outer hair cell. PMID- 8432689 TI - Patterns of innervation of outer hair cells in a chimpanzee: I. Afferent and reciprocal synapses. AB - Three varieties of synaptic specialization, afferent, efferent, and reciprocal, have been demonstrated at the base of outer hair cells of one chimpanzee. The purpose of the present study was to investigate the innervation density of afferent and reciprocal synapses in the three rows and three turns of the organ of Corti. The data presented is based on light and electron microscopy from one aged chimpanzee using serial section electron microscopy. Afferent fibers make contact with outer hair cells as either terminal swellings or en passant contacts. In addition to membrane specialization, presynaptic bodles were present at the majority of afferent synapses. The mean innervation density of afferent endings was highest in the middle turn. Reciprocal endings were found on 74% of all outer hair cells. The average number of reciprocal endings increased from the base to apex and, except in the apical turn, from the first to third row of outer hair cells. On the basis of morphological criteria, endings with a reciprocal synapses were more similar to afferent than to efferent endings. PMID- 8432690 TI - Partial amino acid sequences of organ of Corti proteins OCP1 and OCP2: a progress report. AB - Progress in amino acid sequencing of two low-molecular weight acidic proteins of unknown function which are present at high concentrations in the organ of Corti is reported. These two proteins, provisionally termed OCP1 and OCP2, were originally demonstrated by two-dimensional polyacrylamide gel electrophoresis; their presence at high concentrations in the inner ear sensory epithelia strongly suggests that OCP1 and OCP2 serve some important function in the ear. In the present paper, extension of the amino-terminal sequence of OCP2 to 71 residues is described. In addition, the first results on sequencing of OCP1 are presented. Computer algorithms are used to predict important structural features, and the sequences are analyzed for probable phosphorylation, glycosylation, and Ca binding sites. Projected further studies in immunochemistry and molecular biology of OCP1 and OCP2 based on the amino acid sequencing data are discussed. PMID- 8432691 TI - Tissue specific levels of glucocorticoid receptor within the rat inner ear. AB - Individual, rat inner ear tissues were isolated and processed for determination of levels of glucocorticoid (GR) receptor by an Enzyme Linked Immuno-Sorbant Assay (ELISA). Differing levels of GR receptor between seven sampled inner ear regions were measured. Levels of GR receptors in the spiral ligament tissues were found to be significantly higher compared to all other tissue samples. GR levels in the tissues of stria vascularis and organ of Corti were different from one another but both were statistically higher than those detected in the vestibular tissue samples (dark cell regions, cristae ampullares and maculae utriculi), which had the lowest GR receptor levels measured. Intermediate levels of GR receptor were found in the endolymphatic sac region. It is suggested that the varying levels of inner ear GR receptors may be indicative of differing biological responses among the given tissues, as well as differences in the magnitudes of such responses to circulating glucocorticoids. PMID- 8432692 TI - Two types of sensory hair cell in the saccule of a teleost fish. AB - Previous investigations have demonstrated significant ultrastructural differences in hair cells located in various regions of the utricle of the oscar, Astronotus ocellatus. In this study, we used TEM and SEM to examine cells from the central and marginal regions of the saccule to determine if similar hair cell ultrastructural differences exist in this endorgan. Based upon ultrastructural characteristics, central saccular cells closely resemble utricular striolar cells while marginal cells are intermediate in ultrastructure between striolar and extrastriolar cells of the utricle. PMID- 8432693 TI - Patterns of innervation of outer hair cells in a chimpanzee: II. Efferent endings. AB - A morphometric analysis of the efferent innervation of the outer hair cells in the organ of Corti of one chimpanzee was performed. There was a wide variability in the size of efferent endings which ranged from approximately 0.1 to 4.5 microns 3 in volume. Based on the size distribution of endings, a volume of 1.0 microns 3 was chosen to divide efferent endings into two groups, 'large' and 'small'. The incidence of large efferent fibers decreased from base to apex and from the first to third row of each turn, whereas the incidence of small efferents increased from base to apex and from the first to third row in each turn. This data was interpreted to suggest that at least two types of efferent endings may exist at the base of outer hair cells of the organ of Corti in the chimpanzee. PMID- 8432694 TI - Regulation of the pAD1-encoded sex pheromone response in Enterococcus faecalis: expression of the positive regulator TraE1. AB - pAD1 is a conjugative, 60-kb, hemolysin-bacteriocin plasmid in Enterococcus faecalis that encodes a mating response to a small peptide sex pheromone, cAD1, secreted by potential recipient bacteria. The response is regulated by a cluster of genes that includes a positive regulatory determinant, traE1, able to activate key structural genes involved in the conjugative process. A negative regulatory determinant, traA, affects the expression of traE1 and is sensitive to the pheromone signal. Between the two determinants is a gene, iad, which encodes a small peptide, iAD1, a competitive inhibitor of cAD1. The determinants (traE1-iad traA) are oriented such that iad and traE1 are transcribed in the same direction, opposite that of traA. Transcription of iad and traA starts between these determinants and moves outward in each case. A recent report from our laboratory, dealing with transcriptional fusions in the traE1-iad region (L. T. Pontius and D. B. Clewell, J. Bacteriol. 174:3152-3160, 1992), indicated that traE1 expression may be dependent on transcriptional read-through of a terminator(s) between iad and traE1. The present report provides direct analyses of relevant RNA species before and during induction and shows that indeed transcriptional read-through from iad is important in the initial expression of traE1. However, the data show that once traE1 is activated, it can then be expressed independently, probably because of TraE1 activating its own promoter. This view is also supported by genetic complementation studies. In addition, DNA binding studies with TraA showed that the protein binds to the promoter of iad. Binding of TraA to the region between iad and traE1 could not be detected; however, the involvement of TraA in influencing transcription termination in this region is still not ruled out, since additional factors could be involved. A model for the regulation of the pheromone response is presented. PMID- 8432695 TI - Specific binding of Thiobacillus ferrooxidans RbcR to the intergenic sequence between the rbc operon and the rbcR gene. AB - The presence of two sets (rbcL1-rbcS1 and rbcL2-rbcS2) of rbc operons has been demonstrated in Thiobacillus ferrooxidans Fe1 (T. Kusano, T. Takeshima, C. Inoue, and K. Sugawara, J. Bacteriol. 173:7313-7323, 1991). A possible regulatory gene, rbcR, 930 bp long and possibly translated into a 309-amino-acid protein, was found upstream from the rbcL1 gene as a single copy. The gene is located divergently to rbcL1 with a 144-bp intergenic sequence. As in the cases of the Chromatium vinosum RbcR and Alcaligenes eutrophus CfxR, T. ferrooxidans RbcR is thought to be a new member of the LysR family, and these proteins share 46.5 and 42.8% identity, respectively. Gel mobility shift assays showed that T. ferrooxidans RbcR, produced in Escherichia coli, binds specifically to the intergenic sequence between rbcL1 and rbcR. Footprinting and site-directed mutagenesis experiments further demonstrated that RbcR binds to overlapping promoter elements of the rbcR and rbcL1 genes. The above data strongly support the participation of RbcR in regulation of the rbcL1-rbcS1 operon and the rbcR gene in T. ferrooxidans. PMID- 8432696 TI - Molecular cloning, sequencing, and mapping of the gene encoding protease I and characterization of proteinase and proteinase-defective Escherichia coli mutants. AB - Clones carrying the gene encoding a proteinase were isolated from Clarke and Carbon's collection, using a chromogenic substrate, N-benzyloxycarbonyl-L phenylalanine beta-naphthyl ester. The three clones isolated, pLC6-33, pLC13-1, and pLC36-46, shared the same chromosomal DNA region. A 0.9-kb Sau3AI fragment within this region was found to be responsible for the overproduction of the proteinase, and the nucleotide sequence of the region was then determined. The proteinase was purified to homogeneity from the soluble fraction of an overproducing strain possessing the cloned gene. N-terminal amino acid sequencing of the purified protein revealed that the cloned gene is the structural gene for the protein, with the protein being synthesized in precursor form with a signal peptide. On the basis of its molecular mass (20 kDa), periplasmic localization, and substrate specificity, we conclude this protein to be protease I. By using the gene cloned on a plasmid, a deletion mutant was constructed in which the gene was replaced by the kanamycin resistance gene (Kmr) on the chromosome. The Kmr gene was mapped at 11.8 min, the gene order being dnaZ-adk-ush-Kmr-purE, which is consistent with the map position of apeA, the gene encoding protease I in Salmonella typhimurium. Therefore, the gene was named apeA. Deletion of the apeA gene, either with or without deletion of other proteinases (protease IV and aminopeptidase N), did not have any effect on cell growth in the various media tested. PMID- 8432697 TI - The missing link in phage lysis of gram-positive bacteria: gene 14 of Bacillus subtilis phage phi 29 encodes the functional homolog of lambda S protein. AB - In most bacteriophages of gram-negative bacteria, the phage endolysin is released to its murein substrate through a lesion in the inner membrane. The lesion is brought about by a second phage-encoded lysis function. For the first time, we present evidence that the same strategy is elaborated by a phage of a gram positive bacterium. Thus, there appears to be an evolutionarily conserved lysis pathway for most phages whether their host bacterium is gram negative or gram positive. Phage phi 29 gene 14, the product of which is required for efficient lysis of Bacillus subtilis, was cloned in Escherichia coli. Production of protein 14 in E. coli resulted in cell death, whereas production of protein 14 concomitantly with the phi 29 lysozyme or unrelated murein-degrading enzymes led to lysis, suggesting that membrane-bound protein 14 induces a nonspecific lesion in the cytoplasmic membrane. PMID- 8432698 TI - A complete physical map of a Bacillus thuringiensis chromosome. AB - Bacillus thuringiensis is the source of the most widely used biological pesticide, through its production of insecticidal toxins. The toxin genes are often localized on plasmids. We have constructed a physical map of a Bacillus thuringiensis chromosome by aligning 16 fragments obtained by digestion with the restriction enzyme NotI. The fragments ranged from 15 to 1,350 kb. The size of the chromosome was 5.4 Mb. The NotI DNA fingerprint patterns of 12 different B. thuringiensis strains showed marked variation. The cryIA-type toxin gene was present on the chromosome in four strains, was extrachromosomal in four strains, and was both chromosomal and extrachromosomal in two strains. A Tn4430 transposon probe hybridized to 5 of the 10 cryIA-positive chromosomal fragments, while cryIA and the transposon often hybridized to different extrachromosomal bands. Ten of the strains were hemolytic when grown on agar plates containing human erythrocytes. Nine of the strains were positive when assayed for the presence of Bacillus cereus enterotoxin. We conclude that B. thuringiensis is very closely related to B. cereus and that the distinction between B. cereus and B. thuringiensis should be reconsidered. PMID- 8432699 TI - Analysis of feedback-resistant anthranilate synthases from Saccharomyces cerevisiae. AB - The initial step of tryptophan biosynthesis is catalyzed by the enzyme anthranilate synthase, which in most microorganisms is subject to feedback inhibition by the end product of the pathway. We have characterized the TRP2 gene from a mutant Saccharomyces cerevisiae strain coding for an anthranilate synthase that is unresponsive to tryptophan. Sequence analysis of this TRP2(Fbr) (feedback resistant) allele revealed numerous differences from a previously published TRP2 sequence. However, TRP2(Fbr) was found to differ in only one single-point mutation from its own parent wild type, a C-to-T transition resulting in a serine 76-to-leucine 76 amino acid substitution. Therefore, serine 76 is a crucial amino acid for proper regulation of the yeast enzyme. We constructed additional feedback-resistant enzyme forms of the yeast anthranilate synthase by site directed mutagenesis of the conserved LLES sequence in the TRP2 gene. From analysis of these variants, we propose an extended sequence, LLESX10S, as the regulatory element in tryptophan-responsive anthranilate synthases from prokaryotic and eukaryotic organisms. PMID- 8432700 TI - Organization and transcription of the principal sigma gene (rpoDA) of Pseudomonas aeruginosa PAO1: involvement of a sigma 32-like RNA polymerase in rpoDA gene expression. AB - S1 nuclease mapping and Northern (RNA) hybridization revealed that the rpoDA gene encoding the principal sigma subunit of Pseudomonas aeruginosa PAO1 is transcribed as a monocistronic mRNA of 2 kb and that the transcription from the rpoDA promoter (PC) starts 32 bases upstream from the first nucleotide of the initiation codon during the steady-state growth condition at a low temperature (30 degrees C). The transcript terminates 31 bases downstream from the last nucleotide of the termination codon. When the growth temperature was shifted to 42 degrees C, the synthesis of rpoDA mRNA from a heat shock promoter was transiently induced, although transcription was still occurring from PC during the heat shock period. The transcription initiation site of the heat shock promoter (PHS) is located about 220 bases upstream of the initiation codon of rpoDA. In addition, both promoters were utilized in vitro by RNA polymerase partially purified from heat-shocked cells of P. aeruginosa PAO1. When the rpoDA was introduced into Escherichia coli, the transcription patterns of rpoDA at 30 and 42 degrees C were similar to those observed for P. aeruginosa. These results suggested that the transcription of rpoDA in P. aeruginosa is regulated by the principal RNA polymerase and the heat shock RNA polymerase in response to the environmental temperature. PMID- 8432701 TI - Uptake of 4-toluene sulfonate by Comamonas testosteroni T-2. AB - The mechanism of transport of the xenobiotic 4-toluene sulfonate (TS) in Comamonas testosteroni T-2 was investigated. Rapid uptake of TS was observed only in cells grown with TS or 4-methylbenzoate as a carbon and energy source. Initial uptake rates under aerobic conditions showed substrate saturation kinetics, with an apparent affinity constant (Kt) of 88 microM and a maximal velocity (Vmax) of 26.5 nmol/min/mg of protein. Uptake of TS was inhibited completely by uncouplers and only marginally by ATPase inhibitors and the phosphate analogs arsenate and vanadate. TS uptake was also studied under anaerobic conditions, which prevented intracellular TS metabolism. TS was accumulated under anaerobic conditions in TS grown cells upon imposition of an artificial transmembrane pH gradient (delta pH, inside alkaline). Uptake of TS was inhibited by structurally related methylated and chlorinated benzenesulfonates and benzoates. The results provide evidence that the first step in the degradation of TS by C. testosteroni T-2 is uptake by an inducible secondary proton symport system. PMID- 8432702 TI - Glycerol kinase of Escherichia coli is activated by interaction with the glycerol facilitator. AB - Glycerol transport is commonly cited as the only example of facilitated diffusion across the Escherichia coli cytoplasmic membrane. Two proteins, the glycerol facilitator and glycerol kinase, are involved in the entry of external glycerol into cellular metabolism. The glycerol facilitator is thought to act as a carrier or to form a selective pore in the cytoplasmic membrane, whereas the kinase traps the glycerol inside the cell as sn-glycerol-3-phosphate. We found that the kinetics of glycerol uptake in a facilitator-minus strain are significantly different from the kinetics of glycerol uptake in the wild type. Free glycerol was not observed inside wild-type cells transporting glycerol, and diffusion of glycerol across the cytoplasmic membrane was not the rate-limiting step for phosphorylation in facilitator-minus mutants. Therefore, the kinetics of glycerol phosphorylation are different, depending on the presence or absence of the facilitator protein. We conclude that there is an interaction between the glycerol facilitator protein and glycerol kinase that stimulates kinase activity, analogous to the hexokinase- and glycerol kinase-porin interactions in mitochondria. PMID- 8432703 TI - Cloning, sequencing, and genetic characterization of regulatory genes, rinA and rinB, required for the activation of staphylococcal phage phi 11 int expression. AB - The int gene of staphylococcal bacteriophage phi 11 is the only viral gene responsible for the integrative recombination of phi 11. To study the regulation of int gene expression, we determined the 5' end of the transcript by S1 mapping. The presumed promoter is located just 22 nucleotides upstream of the int open reading frame in a region which is conserved between phi 11 and a closely related staphylococcal phage, L54a. To clone the possible regulatory gene, a vector which contained the reporter gene, xylE, of Pseudomonas putida under the control of the phi 11 int promoter was constructed. Subsequently, a 2-kb DNA fragment from the phi 11 genome, which mapped distal to the int gene, was shown to increase the XylE activity from the int promoter. Sequencing and subsequent deletion analysis of the 2-kb fragment revealed that two phi 11 regulatory genes, rinA and rinB, were both required to activate expression of the int gene. Northern (RNA) analysis suggested that the activation was, at least partly, at the transcriptional level. In addition, one of these regulatory genes, rinA, was capable of activating L54a int gene transcription. PMID- 8432704 TI - The oxygen sensor FixL of Rhizobium meliloti is a membrane protein containing four possible transmembrane segments. AB - Regulation of nitrogen fixation genes in Rhizobium meliloti is mediated by two proteins, FixL and FixJ, in response to oxygen availability. FixL is an oxygen binding hemoprotein with kinase and phosphatase activities that is thought to sense oxygen levels directly and to transmit this signal to FixJ via phosphorylation-dephosphorylation reactions. FixJ controls the expression of other regulatory genes, including nifA, that regulate the transcription of genes required for symbiotic nitrogen fixation. We have been studying the structural and functional features of FixL that are required for oxygen sensing. We constructed mutant derivatives and confirmed that FixL consists of 505 amino acids instead of 464, as originally reported. Hydropathy plots of the full-length protein, together with TnphoA insertional analysis, lead us to propose that FixL is likely to be a polytopic integral membrane protein containing four membrane spanning segments. We have also constructed an N-terminal deletion of the FixL protein whose in vivo activity indicates that the hydrophobic membrane-spanning regions are not absolutely required for oxygen sensing in vivo. We also report that FixL shares homology in its N terminus with other sensor proteins, including KinA from Bacillus subtilis and NtrB from Bradyrhizobium parasponia. The region of homology comprises a 70-amino-acid residue stretch that is also conserved in two oxygenases, P-450 and isopenicillin synthase. PMID- 8432705 TI - Mutations affecting the ability of Escherichia coli Lrp to bind DNA, activate transcription, or respond to leucine. AB - Lrp is a regulatory protein in Escherichia coli that increases expression of some operons and decreases expression of others. Mutations in Lrp were isolated on the basis of their effects on ilvIH, one of the operons regulated positively by Lrp. The ilvIH operon encodes an enzyme involved in the biosynthesis of leucine, valine, and isoleucine, and expression of this operon is repressed when cells are grown in the presence of leucine. Three groups of mutants were isolated. Mutant strains that were resistant to the repressive effects of leucine were termed leucine response mutants. These mutants had changes in the Lrp amino acid sequence between amino acid residues 108 and 149. Mutant strains having low expression of ilvIH in vivo were identified as colonies having reduced expression of a reporter gene. For some of these mutants, called DNA-binding mutants, binding to ilvIH DNA in vitro was markedly reduced. The mutations in these strains caused changes in Lrp between amino acids 16 and 70. Six of ten of these mutations were within a region having a putative helix-turn-helix motif. A third group of mutants had low ilvIH expression in vivo but apparently normal DNA binding in vitro. These mutants were called activation mutants since they affected the ability of Lrp to activate expression. Lrp from these strains had changes in amino acids between residues 76 and 125. This study suggests that Lrp has separate domains responsible for binding DNA, activating transcription, and responding to leucine. PMID- 8432706 TI - Cell division inhibitors SulA and MinCD prevent formation of the FtsZ ring. AB - Immunoelectron microscopy was used to assess the effects of inhibitors of cell division on formation of the FtsZ ring in Escherichia coli. Induction of the cell division inhibitor SulA, a component of the SOS response, or the inhibitor MinCD, a component of the min system, blocked formation of the FtsZ ring and led to filamentation. Reversal of SulA inhibition by blocking protein synthesis in SulA induced filaments led to a resumption of FtsZ ring formation and division. These results suggested that these inhibitors block cell division by preventing FtsZ localization into the ring structure. In addition, analysis of min mutants demonstrated that FtsZ ring formation was also associated with minicell formation, indicating that all septation events in E. coli involve the FtsZ ring. PMID- 8432707 TI - Transferable Streptomyces DNA amplification and coamplification of foreign DNA sequences. AB - The 8.8-kb amplifiable unit of DNA of Streptomyces achromogenes subsp. rubradiris, AUD-Sar 1, which carries 0.8-kb terminal direct repeats and a spectinomycin resistance determinant, can mediate high-level amplification of an AUD-Sar 1-derived 8.0-kb DNA sequence not only in S. achromogenes but also in the heterologous host Streptomyces lividans. This was seen upon introduction of AUD Sar 1 into chloramphenicol-sensitive strains of S. lividans via the temperature sensitive (39 degrees C) plasmid pMT660, which contains the thiostrepton resistance gene tsr. Following the cultivation of transformants at 39 degrees C on media containing spectinomycin, a number of strains which were unable to grow on thiostrepton and which carried the amplified 8.0-kb DNA sequence as arrays of 200 to 300 copies of tandem 8.0-kb repeats were found. Chloramphenicol-resistant strains of S. lividans did not yield amplified sequences under similar conditions. Studies with plasmids carrying inserted antibiotic resistance genes at two sites of AUD-Sar 1 yielded coamplified sequences which contain the inserted DNA. Transformation with a plasmid carrying a 1.0-kb deletion in AUD-Sar 1 followed by growth under similar conditions yielded a 7.0-kb repeated DNA sequence. Southern analysis revealed the absence of vector sequences located on the right side of AUD-Sar 1 in the input plasmids in all examined DNA samples of amplified strains. In contrast, a majority of the samples revealed the presence at unit copy level of AUD-Sar 1 left-adjacent sequences which are part of the input plasmids and in several samples the presence of certain vector sequences located near them. The results suggest input plasmid integration into the S. lividans chromosome prior to the generation of the amplified sequences and the deletion of AUD-Sar 1 adjacent sequences. PMID- 8432708 TI - Characterization of a locus determining the mucoid status of Pseudomonas aeruginosa: AlgU shows sequence similarities with a Bacillus sigma factor. AB - Overproduction of the exopolysaccharide alginate by Pseudomonas aeruginosa results in mucoid colony morphology and is an important virulence determinant expressed by this organism in cystic fibrosis. Mucoidy is transcriptionally regulated by signal transduction systems and histone-like elements. One point of convergence of regulatory elements controlling mucoidy is the algD promoter. A newly described genetic locus required for algD transcription was characterized in this study. This DNA region, cloned from a nonmucoid PAO strain, was initially isolated on the basis of its ability to suppress mucoidy when present on a plasmid. The suppressing activity was observed in several mucoid PAO derivatives, including strain PAO568, in which the mapped muc-2 mutation is responsible for its mucoid phenotype, and in close to 40% of cystic fibrosis strains tested. Protein expression studies detected two polypeptides with apparent molecular masses of 27.5 and 20 kDa encoded by the region required for the suppression activity. The gene encoding the polypeptide with an apparent molecular mass of 27.5 kDa, termed algU, was further characterized. A functional chromosomal copy of algU was found to be necessary for the expression of mucoidy. Insertional inactivation of algU on the chromosome of the mucoid strain PAO568 abrogated alginate production and algD transcription. DNA sequence analysis revealed sequence similarity of the predicted algU gene product with sigma H (Spo0H), a sigma factor involved in the control of sporulation and competence in Bacillus spp. Physical mapping revealed that algU resided on the same SpeI fragment (F) as did the pruAB locus, known to be tightly linked with genetic determinants (muc) which can confer mucoidy in genetic crosses. When the chromosomal algU copy was tagged with a Tcr cassette (algU::Tcr), a tight genetic linkage of algU with pruAB was demonstrated by F116L-mediated generalized transduction. Moreover, algU::Tcr derivatives of PAO568 (originally carrying the muc-2 marker) lost the ability to transfer mucoidy in genetic crosses. These results suggest that algU, a regulator of algD transcription showing sequence similarity to an alternative sigma factor, and the genes immediately downstream of algU may be associated with a locus participating in the differentiation into the mucoid phenotype. PMID- 8432709 TI - Identification of the regulatory sequence of anaerobically expressed locus aeg 46.5. AB - A newly identified anaerobically expressed locus, aeg-46.5, which is located at min 46.5 on Escherichia coli linkage map, was cloned and analyzed. The phenotype of this gene was studied by using a lacZ operon fusion. aeg-46.5 is induced anaerobically in the presence of nitrate in wild-type and narL cells. It is repressed by the narL gene product, as it showed derepressed anaerobic expression in narL mutant cells. We postulate that aeg-46.5 is subject to multiple regulatory systems, activation as a result of anaerobiosis, narL-independent nitrate-dependent activation, and narL-mediated repression. The regulatory region of aeg-46.5 was identified. A 304-bp DNA sequence which includes the regulatory elements was obtained, and the 5' end of aeg-46.5 mRNA was identified. It was verified that the anaerobic regulation of aeg-46.5 expression is controlled on the transcriptional level. Computer analysis predicted possible control sites for the NarL and FNR proteins. The proposed NarL site was found in a perfect-symmetry element. The aeg-46.5 regulatory elements are adjacent to, but divergent from, those of the eco gene. PMID- 8432710 TI - A dominant sulfhydryl-containing protein in the outer membrane of Neisseria gonorrhoeae. AB - By using a method that labels sulfhydryl-containing proteins in situ, we have detected a major outer membrane protein of Neisseria gonorrhoeae at 41 kDa. A protein of this molecular mass has not previously been shown to be a major outer membrane protein in gonococci. In addition, a minor protein rich in cysteinyl residues was detected at 31.5 kDa. PMID- 8432711 TI - Proteins induced by sulfate limitation in Escherichia coli, Pseudomonas putida, or Staphylococcus aureus. AB - Two-dimensional gel electrophoresis of proteins from Escherichia coli, Pseudomonas putida, and Staphylococcus aureus, grown with methionine or one of a variety of organosulfates and organosulfonates as the sole source of sulfur, showed expression of specific sets of 7 to 14 proteins which were not observed during growth with sulfate or cysteine for all three species or with thiocyanate for P. putida and S. aureus. Under the same conditions, arylsulfatase activity in P. putida and S. aureus was seen to increase by up to 140-fold, suggesting that the proteins induced under these conditions may be involved in sulfur metabolism. We propose that these proteins are members of a sulfate starvation-induced stimulon. PMID- 8432712 TI - Freeze-fracture planes of methanogen membranes correlate with the content of tetraether lipids. AB - Methanospirillum hungatei GP1 contained 50% of its ether core lipids (polar lipids less head groups) as tetraether lipids, and its plasma membrane failed to fracture along its hydrophobic domain during freeze-etching. The membrane of Methanosaeta ("Methanothrix") concilii did not contain tetraether lipids and easily fractured to reveal typical intramembranous particles. Methanococcus jannaschii grown at 50 degrees C contained 20% tetraether core lipids, which increased to 45% when cells were grown at 70 degrees C. The frequency of membrane fracture was reduced as the membrane-spanning tetraether lipids approached 45%. As the tetraether lipid content increased, and while fracture was still possible, the particle density in the membrane increased; these added particles could be tetraether lipid complexes torn from the opposing membrane face. The diether membrane (no tetraether lipid) of Methanococcus voltae easily fractured, and the intramembranous particle density was low. Protein-free liposomes containing tetraether core lipids (ca. 45%) also did not fracture, whereas those made up exclusively of diether lipids did split, indicating that tetraether lipids add considerable vertical stability to the membrane. At tetraether lipid concentrations below 45%, liposome bilayers fractured to reveal small intramembranous particles which we interpret to be tetraether lipid complexes. PMID- 8432713 TI - Function of periplasmic copper-zinc superoxide dismutase in Caulobacter crescentus. AB - Caulobacter crescentus is one of a small number of bacterial species that contain a periplasmic copper-zinc superoxide dismutase (CuZnSOD). A C. crescentus mutant, with the CuZnSOD gene interrupted by a promoterless cat gene, was constructed and characterized to analyze CuZnSOD function. Periplasmic SOD does not protect against oxyradical damage in the cytosol or play a major role in maintaining the integrity of the cell envelope. Studies of the effect of sodium citrate on plating efficiency suggest that CuZnSOD protects a periplasmic or membrane function(s) requiring magnesium or calcium. PMID- 8432714 TI - Identification of the Escherichia coli lytB gene, which is involved in penicillin tolerance and control of the stringent response. AB - The Escherichia coli lytB gene, which is involved in penicillin tolerance and control of the stringent response, was identified as a previously described open reading frame designated orf316 located in the ileS-lsp operon (0.4 min on the linkage map). PMID- 8432715 TI - Noninducible Tet repressor mutations map from the operator binding motif to the C terminus. AB - We have developed a new genetic selection system for Tet repressor mutations with a noninducible phenotype for tetracycline (TetRs). Extensive chemical mutagenesis of tetR yielded 93 single-site Tet repressor mutations. They map from residue 23 preceding the alpha-helix-turn-alpha-helix operator binding motif to residue 196 close to the C terminus of the repressor. Thirty-three of the mutations are clustered between residues 95 and 117, and another 27 are clustered between residues 131 to 158. Several of the mutants were characterized quantitatively in vivo for induction by tetracycline and anhydrotetracycline. While all of these are severely reduced in tetracycline-mediated induction, only some of them are affected for anhydrotetracycline-mediated induction. PMID- 8432716 TI - Accumulation of the F plasmid TraJ protein in cpx mutants of Escherichia coli. AB - We report here studies of the cellular control of F plasmid TraJ protein levels, focusing on the effects of chromosomal cpx mutations. The principal conclusion from our results is that the cpx mutations impair accumulation of the TraJ protein, thereby reducing tra gene expression. We measured TraJ activity in vivo by expression of a traY'-'lacZ fusion gene and TraJ protein by immuno-overlay blot. In strains with normal TraJ levels, traY expression and donor-related functions were reduced in cells carrying any of four cpxA mutations. In the strain background used to isolate cpx mutants, these reductions were especially evident in cells grown to high density, when traY expression and donor activity both increased in cpx+ cells. In each of the four cpxA mutants tested, TraJ levels were lower than in the otherwise isogenic cpxA+ strain. In cells grown to high density, the differences ranged from 4-fold in the cpxA6 strain to > 10-fold in the cpxA2, cpxA5, and cpxA9 strains. The cpxA2 mutation had little or no effect on traY expression or on donor-related functions when TraJ was present in excess of its limiting level in F' or Hfr cells or on a mutant traY promoter whose expression in vivo was independent of TraJ. PMID- 8432717 TI - Participation of RAP1 protein in expression of the Saccharomyces cerevisiae arginase (CAR1) gene. AB - Regulated expression of the inducible arginase (CAR1) gene of Saccharomyces cerevisiae has been shown to require three upstream activation sequences (UASs) and an upstream repression sequence, URS1. Two of the UAS elements, UASC1 and UASC2, operate in an inducer-independent manner, while the third, UASI, is inducer dependent. UASC1 and UASC2 were previously shown to contain ABF-1 binding sites that were required for normal transcription. In this work, we demonstrate that UASC1 and UASC2 also contain two and three sites, respectively, that are able to bind RAP1 protein. RAP1 binding to these sites, however, is significantly weaker than that to sites in TEF2 and HMRE. The effects of mutating the sites individually or in combination suggest that at least three of them, two in UASC1 and one in UASC2, probably participate in CAR1 expression. PMID- 8432718 TI - Motility, chemokinesis, and methylation-independent chemotaxis in Azospirillum brasilense. AB - Observations of free-swimming and antibody-tethered Azospirillum brasilense cells showed that their polar flagella could rotate in both clockwise and counterclockwise directions. Rotation in a counterclockwise direction caused forward movement of free-swimming cells, whereas the occasional change in the direction of rotation to clockwise caused a brief reversal in swimming direction. The addition of a metabolizable chemoattractant, e.g., malate or proline, had two distinct effects on the swimming behavior of the bacteria: (i) a short-term decrease in reversal frequency from 0.33 to 0.17 s-1 and (ii) a long-term increase in the mean population swimming speed from 13 to 23 microns s-1. A. brasilense therefore shows both chemotaxis and chemokinesis in response to temporal gradients of some chemoeffectors. Chemokinesis was dependent on the growth state of the cells and may depend on an increase in the electrochemical proton gradient above a saturation threshold. Analysis of behavior of a methionine auxotroph, assays of in vivo methylation, and the use of specific antibodies raised against the sensory transducer protein Tar of Escherichia coli all failed to demonstrate the methylation-dependent pathway for chemotaxis in A. brasilense. The range of chemicals to which A. brasilense shows chemotaxis and the lack of true repellents indicate an alternative chemosensory pathway probably based on metabolism of chemoeffectors. PMID- 8432719 TI - Role of serine 352 in the allosteric response of Serratia marcescens aspartokinase I-homoserine dehydrogenase I analyzed by using site-directed mutagenesis. AB - Aspartokinase I and homoserine dehydrogenase I (AKI-HDI) from Serratia marcescens Sr41 are encoded by the thrA gene as a single polypeptide chain. Previously, a single amino acid substitution of Ser-352 with Phe was shown to produce an AKI HDI enzyme that is not subject to threonine-mediated feedback inhibition. To determine the role of Ser-352 in the allosteric response, the thrA gene was modified by using site-directed mutagenesis so that Ser-352 of the wild-type AKI HDI was replaced by Ala, Arg, Asn, Gln, Glu, His, Leu, Met, Pro, Thr, Trp, Tyr, or Val. The Thr-352 and Pro-352 replacements rendered AKIs sensitive to threonine. The Tyr-352 and Asn-352 substitutions led to activation, rather than inhibition, of AKI by threonine. The other replacements conferred threonine insensitivity on AKI. The threonine sensitivity of HDI was also changed by the amino acid substitutions at Ser-352. The HDI carried by the Tyr-352 mutant AKI HDI was activated by threonine. Single amino acid replacements at Ser-352 by Ala, Asn, Gln, His, Phe, Pro, Thr, or Tyr were introduced into truncated AKI-HDIs containing the AKI and the central regions. The AKI activity of the truncated AKI HDI containing the first 468 amino acid residues was sensitive to threonine, and introduction of the amino acid replacements did not alter the threonine sensitivity of the AKI. Another truncated AKI-HDI containing the first 462 amino acid residues possessed threonine-resistant AKI, whereas the substitutions of Ser 352 with Ala and Pro rendered AKI sensitive to threonine. The replacement of GIn 351 with Phe activated AK1 of the truncated AKI-HDI in the presence of L threonine. These findings suggest that Ser-352 of the central region of AKI-HDI is possibly a key residue involved with the allosteric regulation of both AKI and HDI activities. PMID- 8432720 TI - Paracrystalline inclusions of a novel ferritin containing nonheme iron, produced by the human gastric pathogen Helicobacter pylori: evidence for a third class of ferritins. AB - An abundant 19.3-kDa Helicobacter pylori protein has been cloned, and the sequence is homologous with a ferritin-like protein produced by Escherichia coli K-12. Homologies are also present with a number of eucaryotic ferritins, as well as with the heme group-containing bacterioferritins. All amino acids involved in chelation of inorganic iron by ferritins from humans and other higher species are conserved in the H. pylori protein. Consistent with the structural data indicating an iron-binding function, E. coli overexpressing the H. pylori ferritin-like protein accumulates almost 10 times more nonheme iron than vector controls, and the iron-binding activity copurifies with the 19.3-kDa protein. Immunoelectron microscopy of H. pylori, as well as of E. coli overexpressing the H. pylori gene, demonstrates that the gene product has a cytoplasmic location where it forms paracrystalline inclusions. On the basis of these structural and functional data, we propose that the H. pylori gene product (termed Pfr) forms the basis for a second class of bacterial ferritins designed to store nonheme iron. PMID- 8432721 TI - Structural genes for thiamine biosynthetic enzymes (thiCEFGH) in Escherichia coli K-12. AB - Escherichia coli K-12 synthesizes thiamine pyrophosphate (vitamin B1) de novo. Two precursors [4-methyl-5-(beta-hydroxyethyl)thiazole monophosphate and 4-amino 5-hydroxymethyl-2-methylpyrimidine pyrophosphate] are coupled to form thiamine monophosphate, which is then phosphorylated to make thiamine pyrophosphate. Previous studies have identified two classes of thi mutations, clustered at 90 min on the genetic map, which result in requirements for the thiazole or the hydroxymethylpryimidine. We report here our initial molecular genetic analysis of the thi cluster. We cloned the thi cluster genes and examined their organization, structure, and function by a combination of phenotypic testing, complementation analysis, polypeptide expression, and DNA sequencing. We found five tightly linked genes, designated thiCEFGH. The thiC gene product is required for the synthesis of the hydroxymethylpyrimidine. The thiE, thiF, thiG, and thiH gene products are required for synthesis of the thiazole. These mutants did not respond to 1-deoxy-D-threo-2-pentulose, indicating that they are blocked in the conversion of this precursor compound to the thiazole itself. PMID- 8432722 TI - The Escherichia coli fmt gene, encoding methionyl-tRNA(fMet) formyltransferase, escapes metabolic control. AB - The genetic organization near the recently cloned fmt gene, encoding Escherichia coli methionyl-tRNA(fMet) formyltransferase (J. M. Guillon, Y. Mechulam, J. M. Schmitter, S. Blanquet, and G. Fayat, J. Bacteriol. 174:4294-4301, 1992), has been studied. The fmt gene, which starts at a GUG codon, is cotranscribed with another gene, fms, and the transcription start site of this operon has been precisely mapped. Moreover, the nucleotide sequence of a 1,379-bp fragment upstream from fmt reveals two additional open reading frames, in the opposite polarity. In the range of 0.3 to 2 doublings per h, the intracellular methionyl tRNA(fMet) formyltransferase concentration remains constant, providing, to our knowledge, the first example of a gene component of the protein synthesis apparatus escaping metabolic control. When the gene fusion technique was used for probing, no effect on fmt expression of the concentrations of methionyl tRNA(fMet) formyltransferase or tRNA(fMet) could be found. The possibility that the fmt gene, the product of which is present in excess to ensure full N acylation of methionyl-tRNA(fMet), could be expressed in a constitutive manner is discussed. PMID- 8432723 TI - Oxidized low density lipoprotein inhibits the migration of aortic endothelial cells in vitro. AB - Endothelial cell (EC) migration is a critical and initiating event in the formation of new blood vessels and in the repair of injured vessels. Compelling evidence suggests that oxidized low density lipoprotein (LDL) is present in atherosclerotic lesions, but its role in lesion formation has not been defined. We have examined the role of oxidized LDL in regulating the wound-healing response of vascular EC in vitro. Confluent cultures of bovine aortic EC were "wounded" with a razor, and migration was measured after 18 to 24 h as the number of cells moving into the wounded area and the mean distance of cells from the wound edge. Oxidized LDL markedly reduced migration in a concentration- and oxidation-dependent manner. Native LDL or oxidized LDL with a thiobarbituric acid (TBA) reactivity < 5 nmol malondialdehyde equivalents/mg cholesterol was not inhibitory; however, oxidized LDL with a TBA reactivity of 8-12 inhibited migration by 75-100%. Inhibition was half-maximal at 250-300 micrograms cholesterol/ml and nearly complete at 350-400 micrograms/ml. The antimigratory activity was not due to cell death since it was completely reversed 16 h after removal of the lipoprotein. The inhibitor molecule was shown to be a lipid; organic solvent extracts of oxidized LDL inhibited migration to nearly the same extent as the intact particle. When LDL was variably oxidized by dialysis against FeSO4 or CuSO4, or by UV irradiation, the inhibitory activity correlated with TBA reactivity and total lipid peroxides, but not with electrophoretic mobility or fluorescence (360 ex/430 em). This indicates that a lipid hydroperoxide may be the active species. These results suggest the possibility that oxidized LDL may limit the healing response of the endothelium after injury. PMID- 8432724 TI - Alpha IIb beta 3 integrin dissociation induced by EDTA results in morphological changes of the platelet surface-connected canalicular system with differential location of the two separate subunits. AB - Treatment of human platelets by EDTA (5 mM at 37 degrees C and pH 7.4 for 30 min) induces ultrastructural morphological changes of the surface-connected canalicular system (SCCS). The first consists in dilations of some portions of the channels, whereas the second is represented by collapse of parts of the canaliculi. The collapsed elements of the EDTA treated SCCS are made up of two parallel limiting membranes and a central striated zone. Some of the EDTA treated platelets form microaggregates, the cohesion of which is apparently due to the appearance of pentalaminar interplatelet structures. EDTA treatment is known to induce an irreversible loss of platelet aggregability which is due to irreversible dissociation of the membrane GPIIb-IIIa complexes. In the present study, we looked for involvement of GPIIb-IIIa in the formation of these pentalaminar structures, and were able to demonstrate that the morphological changes described are in fact directly dependent on the EDTA induced dissociation of GPIIb-IIIa complexes. Indeed, we observed that these changes (a) cannot be induced in type I Glanzmann's thrombasthenia, where GPIIb-IIIa complexes are absent, (b) do not appear when human platelets are preincubated with monoclonal anti-GPIIb-IIIa complex-dependent (CD41a) antibodies, which protect the complex from EDTA induced dissociation, (c) appear only at alkaline pH and at 37 degrees C, which corresponds to the range of pH and temperature where EDTA can dissociate GPIIb-IIIa complexes, (d) are accompanied by the disappearance in fluorescence flow cytometry of the heterodimer complex-dependent epitopes, when using anti CD41a antibodies and (e) do not appear in rat platelets, where GPIIb-IIIa does not dissociate after EDTA treatment. Furthermore, using gold-labeled mAbs concomitantly with the addition of EDTA, we observed that almost only GPIIb was present in the collapsed regions of the canaliculi. Using double labeling studies with polyclonal anti-GPIIb antibodies coupled to 10 nm gold particles and polyclonal anti-GPIIIa antibodies coupled to 20 nm gold particles, we observed that while both 10 and 20 nm particles were present in the dilated portions of the canaliculi almost only the small particles, coupled to the anti-GPIIb antibodies, labeled the collapsed portions of the SCCS. On Lowicryl thin sections, polyclonal antibodies against GPIIb labeled the central striated zone while both GPIIb and GPIIIa were found in the dilated portions of the SCCS. All these observations lead us to suggest that homopolymers of GPIIb could be responsible for "zipping" of the SCCS. PMID- 8432725 TI - Dominant negative mutation in cell surface beta 1,4-galactosyltransferase inhibits cell-cell and cell-matrix interactions. AB - In addition to its traditional location within the Golgi complex, beta 1,4 galactosyltransferase (GalTase) is also present on the cell surface, where it is thought to function as a cell adhesion molecule by binding to extracellular oligosaccharide ligands. Recent studies suggest that cells contain two forms of GalTase with distinct cytoplasmic domains. The longer form of GalTase contains a 13-amino acid cytoplasmic extension and is preferentially targeted to the plasma membrane, relative to the shorter GalTase protein that is confined primarily to the Golgi compartment. In this study, we created a dominant negative mutation that interferes with the function of cell surface GalTase by transfecting into cells cDNAs encoding truncated versions of the long form of GalTase containing the complete cytoplasmic and transmembrane domains, but devoid of the catalytic domain. In both F9 embryonal carcinoma cells and Swiss 3T3 fibroblasts, overexpressing the truncated long GalTase (TLGT) protein displaced the endogenous cell surface GalTase from its association with the cytoskeleton, resulting in a loss of intercellular adhesion and cell spreading specifically on matrices that use GalTase as a cell surface receptor. In contrast, overexpressing the analogous truncated short GalTase (TSGT) protein did not affect cell morphology or GalTase activity. In control assays, inducing the TLGT protein had no effect on cell interactions with fibronectin (which is independent of GalTase), or on the cytoskeleton attachment of another matrix receptor (beta 1 integrin), or on overall glycoprotein synthesis, thus eliminating nonspecific effects of the TLGT protein on cellular adhesion and metabolism. These results represent the first molecular manipulation of cell surface GalTase expression and confirm its function as a cell adhesion molecule. These studies further suggest that the cytoskeleton contains a defined, saturable number of binding sites for GalTase, which enables it to function as an adhesion molecule. PMID- 8432726 TI - Identification and characterization of thrombospondin-4, a new member of the thrombospondin gene family. AB - A new member of the thrombospondin gene family, designated thrombospondin-4, has been identified in the Xenopus laevis genome. The predicted amino acid sequence indicates that the protein is similar to the other members of this gene family in the structure of the type 3 repeats and the COOH-terminal domain. Thrombospondin 4 contains four type 2 repeats and lacks the type 1 repeats that are found in thrombospondin-1 and 2. The amino-terminal domain of thrombospondin-4 has no significant homology with the other members of the thrombospondin gene family or with other proteins in the database. RNAse protection analysis establishes that the initial expression of Xenopus thrombospondin-4 is observed during neurulation. Levels of mRNA expression increase twofold during tailbud stages but decrease by the feeding tadpole stage. The size of the thrombospondin-4 message is 3.3 Kb and 3.4 Kb in the frog and human, respectively. Northern blot analysis of human tissues reveals high levels of thrombospondin-4 expression in heart and skeletal muscle, low levels in brain, lung and pancreas and undetectable levels in the placenta, liver and kidney. These data establish the existence of a new member of the thrombospondin gene family that may participate in the genesis and function of cardiac and skeletal muscle. PMID- 8432727 TI - Cytosolic Sec13p complex is required for vesicle formation from the endoplasmic reticulum in vitro. AB - The SEC13 gene of Saccharomyces cerevisiae is required in vesicle biogenesis at a step before or concurrent with the release of transport vesicles from the ER membrane. SEC13 encodes a 33-kD protein with sequence homology to a series of conserved internal repeat motifs found in beta subunits of heterotrimeric G proteins. The product of this gene, Sec13p, is a cytosolic protein peripherally associated with membranes. We developed a cell-free Sec13p-dependent vesicle formation reaction. Sec13p-depleted membranes and cytosol fractions were generated by urea treatment of membranes and affinity depletion of a Sec13p dihydrofolate reductase fusion protein, respectively. These fractions were unable to support vesicle formation from the ER unless cytosol containing Sec13p was added. Cytosolic Sec13p fractionated by gel filtration as a large complex of about 700 kD. Fractions containing the Sec13p complex restored activity to the Sec13p- dependent vesicle formation reaction. Expression of SEC13 on a multicopy plasmid resulted in overproduction of a monomeric form of Sec13p, suggesting that another member of the complex becomes limiting when Sec13p is overproduced. Overproduced, monomeric Sec13p was inactive in the Sec13p-dependent vesicle formation assay. PMID- 8432728 TI - Transient translocation of the cytoplasmic (endo) domain of a type I membrane glycoprotein into cellular membranes. AB - The E2 glycoprotein of the alphavirus Sindbis is a typical type I membrane protein with a single membrane spanning domain and a cytoplasmic tail (endo domain) containing 33 amino acids. The carboxyl terminal domain of the tail has been implicated as (a) attachment site for nucleocapsid protein, and (b) signal sequence for integration of the other alpha-virus membrane proteins 6K and E1. These two functions require that the carboxyl terminus be exposed in the cell cytoplasm (a) and exposed in the lumen of the endoplasmic reticulum (b). We have investigated the orientation of this glycoprotein domain with respect to cell membranes by substituting a tyrosine for the normally occurring serine, four amino acids upstream of the carboxyl terminus. Using radioiodination of this tyrosine as an indication of the exposure of the glycoprotein tail, we have provided evidence that this domain is initially translocated into a membrane and is returned to the cytoplasm after export from the ER. This is the first demonstration of such a transient translocation of a single domain of an integral membrane protein and this rearrangement explains some important aspects of alphavirus assembly. PMID- 8432729 TI - Granzymes A and B are targeted to the lytic granules of lymphocytes by the mannose-6-phosphate receptor. AB - To investigate the question of whether lytic granules share a common biogenesis with lysosomes, cloned cytolytic T cell lines were derived from a patient with I cell disease. The targeting of two soluble lytic granule components, granzymes A and B, was studied in these cells which lack a functional mannose-6-phosphate (Man-6-P) receptor-mediated pathway to lysosomes. Using antibodies and enzymatic substrates to detect the lytic proteins, I-cells were found to constitutively secrete granzymes A and B in contrast to normal cells in which these proteins were stored for regulated secretion. These results suggest that granzymes A and B are normally targeted to the lytic granules of activated lymphocytes by the Man-6 P receptor. In normal cells, the granzymes bear Man-6-P residues, since the oligosaccharide side chains of granzymes A and B, as well as radioactive phosphate on granzyme A from labeled cells, were removed by endoglycosidase H (Endo H). However, in I-cells, granzymes cannot bear Man-6-P and granzyme B acquires complex glycans, becoming Endo H resistant. Although the levels of granzymes A and B in cytolytic I-cell lymphocytes are < 30% of the normal levels, immunolocalization and cell fractionation of granzyme A demonstrated that this reduced amount is correctly localized in the lytic granules. Therefore, a Man-6-P receptor-independent pathway to the lytic granules must also exist. Cathepsin B colocalizes with granzyme A in both normal and I-cells indicating that lysosomal proteins can also use the Man-6-P receptor-independent pathway in these cells. The complete overlap of these lysosomal and lytic markers implies that the lytic granules perform both lysosomal and secretory roles in cytolytic lymphocytes. The secretory role of lytic granules formed by the Man-6-P receptor-independent pathway is intact as assessed by the ability of I-cell lymphocytes to lyse target cells by regulated secretion. PMID- 8432730 TI - The differential degradation of two cytosolic proteins as a tool to monitor autophagy in hepatocytes by immunocytochemistry. AB - The major pathway for cytosolic constituents to enter lysosomes is by autophagy. We used two cytosolic proteins, CuZn superoxide dismutase (SOD) and carbonic anhydrase III (CAIII), as autophagic markers in male rat hepatocytes. We took advantage of the differential presence of the two proteins in autophagic vacuoles because of the high resistance of SOD to lysosomal degradation as compared with CAIII. This allows us to determine the sequence of autophagic vacuole formation. We have double immunogold-labeled SOD and CAIII in cryosections of fasted rat liver and calculated the ratios of SOD over CAIII labeling densities (SOD/CAIII) in autophagic vacuoles (AV), as compared with the cytoplasm. Different classes of AV were defined according to their SOD/CAIII, their morphology, and their additional immunolabeling for the lysosomal markers lgp120 and cathepsin D. Of all AV, 15% exhibited a cytosol-like SOD/CAIII, indicating that degradation had not yet begun. Most of these initial AV (AVi) showed two enveloping membranes. The formation of AVi was prevented by 3-methyladenine, a potent inhibitor of autophagy. Of all AV, 85% showed a SOD/CAIII that exceeded the cytosolic ratio. These single membrane-bound vacuoles were called degradative AV (AVd). Labeling for lysosomal markers allowed the characterization of AV that shared features with both AVi and AVd. These AVi/d had a cytosol-like SOD/CAIII and a double membrane, but showed some labeling for lysosomal markers. Probably these AVi/d represent the recipient compartment for lysosomal components. AVd were positive for cathepsin D and lgp120. We discerned two AVd subclasses. Early AVd with cytosol-like SOD labeling density while CAIII labeling density was consistently lower than in the cytosol. Their size was similar to AVi and AVi/d. Late AVd contained higher SOD concentrations and were mostly larger. Our findings suggest that AV acquire lysosomal constituents by fusion with small nonautophagic structures and that after subsequent elimination of the inner membrane of AVi, degradation starts resulting in the formation of early AVd and late AVd. PMID- 8432732 TI - Flexural rigidity of microtubules and actin filaments measured from thermal fluctuations in shape. AB - Microtubules are long, proteinaceous filaments that perform structural functions in eukaryotic cells by defining cellular shape and serving as tracks for intracellular motor proteins. We report the first accurate measurements of the flexural rigidity of microtubules. By analyzing the thermally driven fluctuations in their shape, we estimated the mean flexural rigidity of taxol-stabilized microtubules to be 2.2 x 10(-23) Nm2 (with 6.4% uncertainty) for seven unlabeled microtubules and 2.1 x 10(-23) Nm2 (with 4.7% uncertainty) for eight rhodamine labeled microtubules. These values are similar to earlier, less precise estimates of microtubule bending stiffness obtained by modeling flagellar motion. A similar analysis on seven rhodamine-phalloidin-labeled actin filaments gave a flexural rigidity of 7.3 x 10(-26) Nm2 (with 6% uncertainty), consistent with previously reported results. The flexural rigidity of these microtubules corresponds to a persistence length of 5,200 microns showing that a microtubule is rigid over cellular dimensions. By contrast, the persistence length of an actin filament is only approximately 17.7 microns, perhaps explaining why actin filaments within cells are usually cross-linked into bundles. The greater flexural rigidity of a microtubule compared to an actin filament mainly derives from the former's larger cross-section. If tubulin were homogeneous and isotropic, then the microtubule's Young's modulus would be approximately 1.2 GPa, similar to Plexiglas and rigid plastics. Microtubules are expected to be almost inextensible: the compliance of cells is due primarily to filament bending or sliding between filaments rather than the stretching of the filaments themselves. PMID- 8432731 TI - The integral membrane protein, ponticulin, acts as a monomer in nucleating actin assembly. AB - Ponticulin, an F-actin binding transmembrane glycoprotein in Dictyostelium plasma membranes, was isolated by detergent extraction from cytoskeletons and purified to homogeneity. Ponticulin is an abundant membrane protein, averaging approximately 10(6) copies/cell, with an estimated surface density of approximately 300 per microns2. Ponticulin solubilized in octylglucoside exhibited hydrodynamic properties consistent with a ponticulin monomer in a spherical or slightly ellipsoidal detergent micelle with a total molecular mass of 56 +/- 6 kD. Purified ponticulin nucleated actin polymerization when reconstituted into Dictyostelium lipid vesicles, but not when a number of commercially available lipids and lipid mixtures were substituted for the endogenous lipid. The specific activity was consistent with that expected for a protein comprising 0.7 +/- 0.4%, by mass, of the plasma membrane protein. Ponticulin in octylglucoside micelles bound F-actin but did not nucleate actin assembly. Thus, ponticulin-mediated nucleation activity was sensitive to the lipid environment, a result frequently observed with transmembrane proteins. At most concentrations of Dictyostelium lipid, nucleation activity increased linearly with increasing amounts of ponticulin, suggesting that the nucleating species is a ponticulin monomer. Consistent with previous observations of lateral interactions between actin filaments and Dictyostelium plasma membranes, both ends of ponticulin-nucleated actin filaments appeared to be free for monomer assembly and disassembly. Our results indicate that ponticulin is a major membrane protein in Dictyostelium and that, in the proper lipid matrix, it is sufficient for lateral nucleation of actin assembly. To date, ponticulin is the only integral membrane protein known to directly nucleate actin polymerization. PMID- 8432733 TI - Observation and quantification of individual microtubule behavior in vivo: microtubule dynamics are cell-type specific. AB - Recent experiments have demonstrated that the behavior of the interphase microtubule array is cell-type specific: microtubules in epithelial cells are less dynamic than microtubules in fibroblasts (Pepper-kok et al., 1990; Wadsworth and McGrail, 1990). To determine which parameters of microtubule dynamic instability behavior are responsible for this difference, we have examined the behavior of individual microtubules in both cell types after injection with rhodamine-labeled tubulin subunits. Individual microtubules in both cell types were observed to grow, shorten, and pause, as expected. The average amount of time microtubules remained within the lamellae of CHO fibroblasts, measured from images acquired at 10-s intervals, was significantly shorter than the average amount of time microtubules remained within lamellae of PtK1 epithelial cells. Further analysis of individual microtubule behavior from images acquired at 2-s intervals reveals that microtubules in PtK1 cells undergo multiple brief episodes of growth and shortening, resulting in little overall change in the microtubule network. In contrast, microtubules in lamellae of CHO fibroblasts are observed to undergo fewer transitions which are of longer average duration, resulting in substantial changes in the microtubule network over time. A small subset of more stable microtubules was also detected in CHO fibroblasts. Quantification of the various parameters of dynamic instability behavior from these sequences demonstrates that the average rates of both growth and shortening are significantly greater for the majority of microtubules in fibroblasts than for microtubules in epithelial cells (19.8 +/- 10.8 microns/min, 32.2 +/- 17.7 microns/min, 11.9 +/- 6.5 microns/min, and 19.7 +/- 8.1 microns/min, respectively). The frequency of catastrophe events (1/interval between catastrophe events) was similar in both cell types, but the frequency of rescue events (1/time spent shrinking) was significantly higher in PtK1 cells. Thus, individual microtubules in PtK1 lamellae undergo frequent excursions of short duration and extent, whereas most microtubules in CHO lamellae undergo more extensive excursions often resulting in the appearance or disappearance of microtubules within the field of view. These observations provide the first direct demonstration of cell-type specific behavior of individual microtubules in living cells, and indicate that these differences can be brought about by modulation of the frequency of rescue. These results directly support the view that microtubule dynamic instability behavior is regulated in a cell-type specific manner. PMID- 8432734 TI - NuMA is required for the proper completion of mitosis. AB - NuMA is a 236-kD intranuclear protein that during mitosis is distributed into each daughter cell by association with the pericentrosomal domain of the spindle apparatus. The NuMA polypeptide consists of globular head and tail domains separated by a discontinuous 1500 amino acid coiled-coil spacer. Expression of human NuMA lacking its globular head domain results in cells that fail to undergo cytokinesis and assemble multiple small nuclei (micronuclei) in the subsequent interphase despite the appropriate localization of the truncated NuMA to both the nucleus and spindle poles. This dominant phenotype is morphologically identical to that of the tsBN2 cell line that carries a temperature-sensitive mutation in the chromatin-binding protein RCC1. At the restrictive temperature, these cells end mitosis without completing cytokinesis followed by micronucleation in the subsequent interphase. We demonstrate that the wild-type NuMA is degraded in the latest mitotic stages in these mutant cells and that NuMA is excluded from the micronuclei that assemble post-mitotically. Elevation of NuMA levels in these mutant cells by forcing the expression of wild-type NuMA is sufficient to restore post-mitotic assembly of a single normal-sized nucleus. Expression of human NuMA lacking its globular tail domain results in NuMA that fails both to target to interphase nuclei and to bind to the mitotic spindle. In the presence of this mutant, cells transit through mitosis normally, but assemble micronuclei in each daughter cell. The sum of these findings demonstrate that NuMA function is required during mitosis for the terminal phases of chromosome separation and/or nuclear reassembly. PMID- 8432735 TI - BIMA, a TPR-containing protein required for mitosis, localizes to the spindle pole body in Aspergillus nidulans. AB - The Aspergillus nidulans bimA gene is required for mitosis. Loss of function mutations in bimA cause cells to arrest growth with condensed chromatin and a short, metaphaselike mitotic spindle. bimA is a member of a gene family defined by a repeated motif called the Tetratrico Peptide Repeat (TPR), which is found in genes from bacteria, yeast and insects. Several yeast TPR genes are also required for mitosis, including Saccharomyces cerevisiae CDC27 and Schizosaccharomyces pombe nuc2+, which appear to be functional homologs of bimA. We have developed antisera specific to the bimA protein (BIMA) and have characterized BIMA by western blot and immunocytochemical analyses. BIMA is heterogeneous in apparent molecular weight, consisting of a major 90-kD species and at least two minor species of approximately 105 kD. The results of BIMA localization by immunofluorescence microscopy depend on the level of BIMA expression. Overexpression of BIMA, which had no deleterious affect on growth or mitosis, resulted in localization of BIMA on or throughout most nuclei. Nuclear staining was granular, and overlapped but was not completely coincident with DNA staining by DAPI. In contrast, when expressed at normal levels, BIMA colocalized with the spindle pole body (SPB). BIMA localized to the SPB in a cell cycle independent manner. These results show that BIMA is either associated with or is a component of the SPB, and they suggest that BIMA functions at the spindle poles to promote the onset of anaphase. PMID- 8432736 TI - Role of the latent TGF-beta binding protein in the activation of latent TGF-beta by co-cultures of endothelial and smooth muscle cells. AB - Transforming growth factor beta (TGF-beta) is released from cells in a latent form consisting of the mature growth factor associated with an aminoterminal propeptide and latent TGF-beta binding protein (LTBP). The endogenous activation of latent TGF-beta has been described in co-cultures of endothelial and smooth muscle cells. However, the mechanism of this activation remains unknown. Antibodies to native platelet LTBP and to a peptide fragment of LTBP inhibit in a dose-dependent manner the activation of latent TGF-beta normally observed when endothelial cells are cocultured with smooth muscle cells. Inhibition of latent TGF-beta activation was also observed when cells were co-cultured in the presence of an excess of free LTBP. These data represent the first demonstration of a function for the LTBP in the extracellular regulation of TGF-beta activity and indicate that LTBP participates in the activation of latent TGF-beta, perhaps by concentrating the latent growth factor on the cell surface where activation occurs. PMID- 8432737 TI - Signal transduction in bacteria. Prospects symposium. PMID- 8432738 TI - Low fluences of ultraviolet irradiation stimulate HeLa cell surface aminopeptidase and candidate "TGF alpha ase" activity. AB - Several forms of perturbation result in the release of bioactive molecules into the microenvironment of injured cells to mediate the inflammatory or reparative reactions which restore normal tissue structure and function. Amongst other products, ultraviolet irradiation (UV) causes the release of the growth factor TGF alpha from a variety of epithelial cell sources, apparently by a post translational mechanism. Here we have explored the hypothesis that UV results in the activation of cell surface proteases which may then be capable of excising mature TGF alpha from its plasma membrane-bound precursor. Using a recently described, sensitive assay of peptidase activity tailored to the substrate requirements for cleavage of the scissile bonds in proTGF alpha, we have found that nonlethal fluences of UV (< 12 Jm-2) to HeLa cell cultures are followed by large increases in cell surface proteolytic activities. Amongst these, endopeptidase activity produces a similar product profile from the nonapeptide substrate to that of human leukocyte elastase, an enzyme previously shown to be capable of releasing a bioactive, mature form of TGF alpha from its cell-bound precursor. However, in addition to this candidate "TGFase" activity, cell surface aminopeptidase activity was also very significantly increased. The increase in the two classes of peptidase function differed in the timing of their responses. Aminopeptidase activation occurred immediately following UV, peaking after some 15-20 h, whereas the increase in endopeptidase activity lagged 6 h behind, cresting after 20-24 h. No evidence for a role for aminopeptidase in the activation of the endopeptidase could be found. Also, there was no increase in the total proteolytic activity demonstratable in cell extracts following UV. Attempts to interrupt the UV peptidase activation by inhibiting protein synthesis with cycloheximide were unsuccessful; rather, the inhibitor itself caused an increase in both classes of peptidase activity during the first 20 h. Unlike the UV response, both the aminopeptidase and endopeptidase ectoactivities increased simultaneously within a few hours of introducing cycloheximide into the medium of unirradiated cultures. The cycloheximide induced activity peaked after 20 h. Interestingly, cycloheximide alone has previously been shown to potentiate TGF alpha release from a cell line producing its precursor constitutively. These data suggest that both UV and cycloheximide can initiate reactions in HeLa cells which result in ectopeptidase activation of a global nature. Since both agents result in rapid interruption of DNA synthesis, it is possible that this cell surface proteolytic response may be analogous to, or part of, the "mammalian genetic stress response".(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8432739 TI - The role of phosphorylation of HPr, a phosphocarrier protein of the phosphotransferase system, in the regulation of carbon metabolism in gram positive bacteria. AB - HPr of the Gram-positive bacterial phosphotransferase system (PTS) can be phosphorylated by an ATP-dependent protein kinase on a serine residue or by PEP dependent Enzyme 1 on a histidyl residue. Both phosphorylation events appear to influence the metabolism of non-PTS carbon sources. Catabolite repression of the gluconate (gnt) operon of B. subtilis appears to be regulated by the former phosphorylation event, while glycerol kinase appears to be regulated by the latter phosphorylation reaction. The extent of our understanding of these processes will be described. PMID- 8432740 TI - Catabolite repression in the gram-positive bacteria: generation of negative regulators of transcription. AB - Operons subject to catabolite repression (CR) in the gram-positive bacteria appear to be transcriptionally regulated by negative acting catabolite repressors. Cis elements within the promoter regions of a few CR operons have been identified as the target sequences for these repressors. It has also been proposed that sequences internal to the transcriptional unit may represent targets for recognition of the operons as catabolite repressible. The precise mechanism(s) of regulation have yet to be worked out. PMID- 8432741 TI - Eukaryotic-like protein serine/threonine kinases in Myxococcus xanthus, a developmental bacterium exhibiting social behavior. AB - Myxococcus xanthus, a gram-negative bacterium exhibits a spectacular life cycle and social behavior. Its developmental cycle and multicellular morphogenesis resemble those of eukaryotic slime molds such as Dictyostelium discoideum. On the basis of this resemblance, we explored the existence of eukaryotic-like protein serine/threonine kinases which are known to play important roles in signal transduction during development of D. discoideum. It was indeed found that M. xanthus contains a large family of protein serine/threonine kinases related to the eukaryotic enzymes. This is the first unambiguous demonstration of eukaryotic like serine/threonine kinases in the prokaryotes. PMID- 8432742 TI - Gene regulation by phosphate in enteric bacteria. AB - The Escherichia coli phosphate (PHO) regulon includes 31 (or more) genes arranged in eight separate operons. All are coregulated by environmental (extra-cellular) phosphate and are probably involved in phosphorus assimilation. Pi control of these genes requires the sensor PhoR, the response regulator PhoB, the binding protein-dependent Pi-specific transporter Pst, and the accessory protein PhoU. During Pi limitation, PhoR turns on genes of the PHO regulon by phosphorylating PhoB that in turn activates transcription by binding to promoters that share an 18-base consensus PHO Box. When Pi is in excess, PhoR, Pst, and PhoU together turn off the PHO regulon, presumably by dephosphorylating PhoB. In addition, two Pi-independent controls that may be forms of cross regulation turn on the PHO regulon in the absence of PhoR. The sensor CreC, formerly called PhoM, phosphorylates PhoB in response to some (unknown) catabolite, while acetyl phosphate may directly phosphorylate PhoB. Cross regulation of the PHO regulon by CreC and acetyl phosphate may be examples of underlying control mechanisms important for the general (global) control of cell growth and metabolism. PMID- 8432743 TI - The phosphorelay signal transduction pathway in the initiation of Bacillus subtilis sporulation. AB - The formation of spores in Bacillus subtilis is a developmental process under genetic control. The decision to either divide or sporulate is regulated by the state of phosphorylation of the SpoOA transcription factor. Phosphorylated SpoOA (SpoOA approximately P) is both a repressor and an activator of transcription depending on the promoter it is affecting. SpoOA approximately P is the end product of the phosphorelay, a signal transduction system linking environmental information to the activation of sporulation. Activation or deinhibition of two ATP-dependent kinases, KinA and KinB, to phosphorylate the SpoOF secondary messenger initiates the phosphorelay. SpoOF approximately P is the substrate for the SpoOB protein, a phosphoprotein phosphotransferase which transfers the phosphate group to SpoOA. The SpoOA approximately P formed from this pathway orchestrates transcription events during the initial stage of spore development through direct effects on a variety of promoters and through the use of other transcription factors, termed transition state regulators, whose activity it controls. Because commitment to sporulation has serious cellular programming consequences and is not undertaken capriciously, the phosphorelay is subject to a variety of complex controls on the flow of phosphate through its components. PMID- 8432744 TI - Regulatory interactions involving the proteins of the phosphotransferase system in enteric bacteria. AB - Sugar uptake and cytoplasmic inducer generation as well as cyclic AMP synthesis are regulated by the phosphoenolpyruvate:sugar phosphotransferase system (PTS) in Gram-negative enteric bacteria. In these organisms, the free form of the glucose specific Enzyme IIA (IIAglc) of the PTS, which can be phosphorylated on a histidyl residue by PEP and the PTS energy coupling proteins, inhibits the activities of non-PTS carbohydrate permeases and catabolic enzymes. By contrast, the phosphorylated form of IIAglc appears to activate adenylate cyclase, the cyclic AMP biosynthetic enzyme. What is known of the molecular details of these regulatory interactions will be summarized, and a novel regulatory mechanism involving the fructose repressor, FruR, which controls the transcription of genes encoding enzymes which catalyze reactions in central pathways of carbon metabolism, will be presented. PMID- 8432745 TI - Signal transduction in chemotaxis mediated by the bacterial phosphotransferase system. AB - Gram-negative bacteria are able to respond chemotactically to carbohydrates which are substrates of the bacterial phosphoenolpyruvate:sugar phosphotransferase system (PTS). The mechanism of signal transduction in PTS-mediated chemotaxis is different from the well-studied mechanism involving methyl-accepting chemotaxis proteins (MCPs). In PTS-mediated chemotaxis, carbohydrate transport is required, and phosphorylation seems to be involved in both excitation and adaptation. In this review the roles of the components of the PTS in chemotactic signal transduction are discussed. PMID- 8432746 TI - ATP-dependent protein kinases in bacteria. AB - Protein phosphorylation has been shown to occur in over fifty different bacterial species and, therefore, seems to be a universal device among prokaryotes. Most of the protein kinases responsible for this modification of proteins share the common property of using adenosine triphosphate as phosphoryl donor. However, they differ from one another in a number of structural and functional aspects. Namely, they exhibit a varying acceptor amino acid specificity and can be classified, on this basis, in three main groups: protein-histidine kinases, protein-serine/threonine kinases and protein-tyrosine kinases. PMID- 8432747 TI - Three-dimensional structures of the central regulatory proteins of the bacterial phosphotransferase system, HPr and enzyme IIAglc. AB - Enzyme IIA and HPr are central regulatory proteins of the bacterial phosphoenolpyruvate:sugar phosphotransferase (PTS) system. Three-dimensional structures of the glucose enzyme IIA domain (IIAglc) and HPr of Bacillus subtilis and Escherichia coli have been studied by both X-ray crystallography and Nuclear Magnetic Resonance (NMR) Spectroscopy. Phosphorylation of HPr of B. subtilis and IIAglc of E. coli have also been characterized by NMR spectroscopy. In addition, the binding interfaces of B. subtilis HPr and IIAglc have been identified from backbone chemical shift changes. This paper reviews these recent advances in the understanding of the three-dimensional structures of HPr and IIAglc and their interaction with each other. PMID- 8432748 TI - The physiology of cancer cells. PMID- 8432749 TI - The hypercoagulable states. AB - In most cases, acute venous thrombosis has a straightforward etiology--for example, the patient who has had prolonged bed rest with a broken leg and received no heparin. A significant minority of patients, however, have an inherited biochemical deficiency or an acquired disorder that increases the risk of thrombosis. Some general guidelines suggest when to suspect such defects and what tests to apply. PMID- 8432750 TI - Why segregation now? PMID- 8432751 TI - Dvorak arrangement. PMID- 8432752 TI - Guardians of the planet? PMID- 8432753 TI - Growth mechanisms and cancer progression. AB - In the final stages of malignant progression, tumor cell growth mechanisms become self-contained, making the cells impervious to attempts at growth control by physicians or the host. Such tactics might work better in the early stages of metastasis, when these cells are still responsive to outside influences. PMID- 8432754 TI - Weight loss and ichthyosis in an elderly patient. PMID- 8432755 TI - Nonsurgical management of peripheral arterial disease. PMID- 8432756 TI - The evaluation of recurrent meningitis. PMID- 8432757 TI - Gonorrhea: clinical and public health issues. PMID- 8432758 TI - Evaluation of culture-negative endocarditis. PMID- 8432759 TI - Diagnostic dilemmas in obstructive airway disease. PMID- 8432760 TI - Some lessons of lung transplantation. PMID- 8432761 TI - Acute neurologic deficit in a battered woman. PMID- 8432762 TI - Rapid detection of cymbidium mosaic virus by the polymerase chain reaction (PCR). AB - A direct, simple and sensitive method was developed for the detection of cymbidium mosaic virus (CyMV), based on the polymerase chain reaction (PCR). Two oligonucleotide primers were selected from regions that are homologous to potexviruses and CyMV, and used to hybridize with purified viral RNA and particles. This resulted in the amplification of a 313 bp fragment after 30 cycles of PCR in all samples. A less prominent fragment of 227 bp was also obtained due to mispriming of the second primer. The amplified fragments were easily seen in an agarose gel when stained with ethidium bromide. As little as 1 fg of viral RNA (about 200 target copies) or 10 fg of purified virus (approximately 130 viral particles) were detectable. For CyMV infected orchid leaf tissues, 10 microliters aliquots of 1 mm3 tissue homogenate in 1 ml could be detected routinely. All reverse transcription and amplification reactions were carried out in a single tube and results can be obtained within 5 h. PMID- 8432763 TI - New HIV plaque titration; application to the assay of neutralizing antibody. AB - A simple, sensitive and accurate plaque assay was developed using HPB-Ma, a variant of the human T-cell line HPB-ALL, which becomes adherent to the substratum after infection with an amphotropic murine sarcoma virus (MSVa). The simplicity of this novel plaque assay allowed us to examine a large number of serum samples from patients with HIV infection for neutralizing antibody activity against two human immunodeficiency virus type-1 (HIV-1) strains. During the progression of clinical disease, the neutralizing activity in the sera from two individual patients remained unchanged or increased. A patient with a known time of HIV infection produced cross-neutralizing antibody at 25-34 weeks. The neutralizing activity in the sera from 17 asymptomatic carriers, four patients with AIDS-related complex and four AIDS patients was also examined and was found to be unrelated to the clinical stage. PMID- 8432764 TI - Intertypic differentiation and detection of intratypic variants among canine and phocid morbillivirus isolates by kinetic neutralization using a novel immunoplaque assay. AB - Intertypic antigenic differences and the intratypic variability of the closely related canine (CVD) and phocid distemper viruses (PDV) were examined using a molecular (monoclonal antibodies specific for the H- and F-glycoproteins) and a functional (kinetic neutralization, KN) approach. KN studies were carried out using a novel immunoplaque technique which combined conventional plaque assay and antigen-specific enzyme-immunostaining techniques. Morbillivirus isolates of canine and phocid origin clearly formed two separate groups. Minor antigenic differences were also evident within each cluster. A distemper isolate of mustelid origin was distinguishable from both CDV- and PDV-like prototype viruses by kinetic neutralization. PMID- 8432765 TI - A polymerase chain reaction method adapted for selective amplification and cloning of 3' sequences of potyviral genomes: application to dasheen mosaic virus. AB - 'Universal' degenerate oligonucleotide primers were used to amplify cDNA sequences containing the 3' untranslated region (3' UTR) and a portion of the coat protein gene sequence of dasheen mosaic potyvirus (DMV). These primers were based on the conserved WCIEN and QMKAAA 'boxes' of the potyviral coat protein and the poly-A tail found at the 3' end of the genome. The forward genome-sense primers were designed taking into consideration the codon degeneracy of the WCIEN and QMKAAA residues for several potyviruses. The anti-sense reverse primer has 21 T residues followed by either A, C or G at the 3' end to ensure specific priming at the end of the 3' UTR and beginning of the poly-A tail. The specificity of amplification was verified using the known potyviruses (watermelon mosaic 2 and soybean mosaic viruses). To demonstrate the applicability of this method, the 3' UTR of the unsequenced DMV was amplified, cloned and sequenced. Sequence comparisons with other potyviral 3' UTRs revealed DMV to be quite distinct: nucleotide sequence similarities of only 34% to 44% were found with sequenced viruses indicating no close affinities with any other potyvirus. The potyvirus 3' sequence amplification procedure is simple and rapid, is potentially useful in developing virus specific probes and may be used to differentiate strains and species of potyviruses on the basis of the 3' UTR sequences. PMID- 8432766 TI - Clinical review 42: Hypoglycemias. PMID- 8432767 TI - Sex hormone-binding globulin: a marker for hyperinsulinemia and/or insulin resistance? PMID- 8432768 TI - Level of sex hormone-binding globulin is positively correlated with insulin sensitivity in men with type 2 diabetes. AB - The level of sex hormone-binding globulin (SHBG) is associated with glucose metabolism in nondiabetic women and men, and the finding of low SHBG levels is suggested to be a predictor of the development of type 2 (noninsulin-dependent) diabetes mellitus. To further assess the relationship between SHBG levels and glucose metabolism, we measured serum concentrations of sex hormones and SHBG in 23 well characterized diabetic men, and studied the relationship between these variables and parameters of glucose and lipid metabolism. Insulin sensitivity was estimated using the hyperinsulinemic euglycemic glucose clamp technique. There was a strong positive correlation between the level of SHBG and the sensitivity to insulin in these individuals (r = 0.74; P < 0.001), which was independent of obesity and abdominal fat accumulation. Controlling for the effect of fasting C peptide and insulin levels did not change the correlation coefficient significantly. SHBG levels did not correlate with levels of free testosterone (F T), free estradiol (F-E2), or F-T/F-E2 ratio. F-E2 was positively correlated with levels of diastolic blood pressure and triglycerides (r = 0.44; P < 0.05 and r = 0.62; P < 0.001, respectively). These findings support earlier observations that associate insulin resistance with levels of SHBG, and for the first time demonstrate a direct correlation between sensitivity to insulin and SHBG levels in men with type 2 diabetes. PMID- 8432769 TI - Relationship of insulin secretory pulses to sex hormone-binding globulin in normal men. AB - Insulin has emerged as a regulator of sex hormone-binding globulin (SHBG) production in vitro and in vivo. A role for insulin in regulating SHBG exists in insulin resistant states such as obesity and polycystic ovary syndrome. The relationship of in vivo insulin secretion rates to SHBG levels in healthy normal men is less well documented. Hepatic synthesis of SHBG may be influenced by quantitative insulin exposure as well as qualitative characteristics such as frequency and amplitude of insulin secretory pulses. The present study was undertaken to assess these relationships in 10 normal men. Adiposity was determined by the body mass index and fat distribution by the waist hip ratio. Peripheral insulin sensitivity was determined by the euglycemic clamp technique at an insulin infusion rate of 287 pmol/min.m2. SHBG levels were determined in the fasting state by RIA. Arterialized venous samples for C-peptide were obtained every 2 min for 90 min in the basal state. Individual C-peptide kinetics were derived after a bolus injection of biosynthetic human C-peptide and a previously validated two compartmental model. Insulin secretion rates at each time point were calculated using the plasma C-peptide values and the C-peptide kinetics. Insulin secretion rates were unrelated to SHBG concentrations (r = -0.29, P > 0.05). The insulin secretory pulse interval had a significant positive association with SHBG levels (r = 0.86, P < 0.05). Insulin secretory pulse amplitude, body mass index, waist hip ratio, and peripheral insulin sensitivity were not associated with SHBG concentrations in a regression analysis. We postulate that insulin secretory pulse frequency may be an important determinant of SHBG synthesis in normal man. PMID- 8432770 TI - Interrelation between plasma sex hormone-binding globulin and plasma insulin in healthy adult women: the telecom study. AB - In order to study the relationship between plasma sex-hormone-binding globulin (SHBG) and insulin levels in healthy women, we investigated the association between plasma SHBG and insulin in an occupational sample of 786 nonhormone-using women. Levels of plasma SHBG showed a stepwise decrease with increasing fasting plasma insulin in premenopausal as well as in postmenopausal women. In these cross-sectional data, this significant negative relationship between SHBG and insulin was shown to be independent of age, body mass index, subscapular skinfold, fasting and 2-h plasma glucose in both groups. The etiology and the consequences of this inverse association between SHBG and insulin are unclear. Prospective and clinical studies in women will be necessary to determine the direction and causal nature of the association between SHBG and insulin, as well as its mechanism and its physiological and/or pathophysiological consequences. PMID- 8432771 TI - Predicting relapse after transsphenoidal surgery for Cushing's disease. AB - Although selective transsphenoidal surgery is an effective treatment for pituitary-dependent Cushing's syndrome the definition of cure as distinct from improvement is unclear. Complete tumor removal should be associated with very low serum cortisol levels because of long-term suppression of normal corticotrophs but the optimum timing of this investigation after surgery has not been established. Eleven consecutive patients with surgical and histological confirmation of a corticotroph adenoma removed at transsphenoidal surgery for proven Cushing's disease were studied with 0900 h serum cortisol levels at 5-14 days and 6-12 weeks postoperatively. Patients were maintained on hydrocortisone 10 mg three times daily (final dose at 1800 h) pending recovery of the hypothalamic-pituitary axis which was assessed by periodic short tetracosactrin tests and continued remission of the condition was confirmed by low dose dexamethasone suppression testing. All patients achieved clinical resolution of their disease but four subsequently developed biochemical evidence of recurrence with incomplete suppression on low dose dexamethasone testing at 2-48 months after surgery. These patients had 0900 h serum cortisol levels of 124, 95, 186, and 265 nmol/L at 5-14 days and 334, 52, 130, and 240 nmol/L at 6-12 weeks postoperatively. The remaining seven patients, who are in remission after 8-83 (median 24) months of follow-up, demonstrated 0900 h serum cortisol levels of 30 75 (median 31) nmol/L at 5-14 days but lower levels at 6-12 weeks (< 20 nmol/L in three patients and 22, 30, 30, and 33 nmol/L in the remainder). In this series, serum cortisol measurements at 6-12 weeks after transsphenoidal surgery for Cushing's disease are lower than levels obtained within 2 weeks of surgery and appear to give better discrimination of continuing remission; levels less than 35 nmol/L suggest a favorable long-term outcome. PMID- 8432772 TI - Regulation of growth hormone binding protein in man: comparison of gel chromatography and immunoprecipitation methods. AB - GH circulates in part bound to a high affinity binding protein (GHBP). Gel chromatography is the established method for measuring GH binding activity in plasma, but is slow and tedious. The separation of bound from free GH by immunoprecipitation using a monoclonal antibody to the GH receptor may be a more practical alternative. We have examined the effects of GH and estrogen status on GHBP measured in 24-h pool samples and compared results obtained from gel filtration and immunoprecipitation. GHBP activity (percent specific binding of [125I]GH) was measured in normal, GH-deficient, and acromegalic subjects; and in two groups of postmenopausal women before and after oral (ethinyl estradiol 20 micrograms daily) or transdermal (17 beta-estradiol 100 micrograms daily) estrogen therapy. GHBP activity was not significantly different between normal, GH-deficient, and acromegalic subjects matched for age and sex. Neither GH administration to GH-deficient and normal subjects, nor octreotide treatment of patients with acromegaly, significantly altered GHBP activity. Oral estrogen treatment significantly increased GHBP activity. This change was associated with an increase in binding capacity (P = 0.001) but not affinity, as revealed by Scatchard analysis. GHBP activity did not change significantly with transdermal estrogen therapy. GHBP activity obtained by the two methods was significantly correlated (n = 70, r = 0.92, P = 0.001) although values for the antibody method were 25% higher. Similarly, capacity estimates were highly correlated (r = 0.90, P = 0.0001), with values by immunoprecipitation being 40% higher. We conclude that GH secretory status is not a determinant of GHBP. Oral estrogens increase GHBP activity through an increase in capacity and not affinity. The estrogen effect is route dependent and the oral response is likely to reflect a first pass hepatic effect. The higher binding activity and capacity estimated from immunoprecipitation are likely to reflect a more rapid separation process thereby minimizing dissociation of GHBP complex. Immunoprecipitation offers the advantages of simplicity, convenience, and accuracy for the measurement of GH binding activity and GHBP concentrations in serum. PMID- 8432773 TI - Treatment of adults with growth hormone (GH) deficiency with recombinant human GH. AB - In a double blind, cross-over placebo-controlled trial, we studied the effects of 26 weeks of replacement therapy with recombinant human GH on body composition, metabolic parameters, and well-being in 10 patients with adult-onset GH deficiency (GHD). All patients received appropriate thyroid, adrenal, and gonadal replacement therapy. The dose of recombinant human GH was 0.25-0.5 U/kg.week (0.013-0.026 mg/kg.day) and was administered sc daily at bedtime. One patient was withdrawn from the study because of edema and atrial fibrillation. Body composition was estimated with three independent methods: computed tomography, bioelectric impedance, and total body potassium combined with total body water assessments. The Comprehensive Psychological Rating Scale and the Symptom Check List-90 were used to assess any change in psychopathology. After 26 weeks of treatment, adipose tissue (AT) mass decreased 4.7 kg (P < 0.001). Subcutaneous AT decreased by an average of 13%, whereas visceral AT was reduced by 30%. Muscle volume increased by 2.5 kg (5%; P < 0.05). According to the four-compartment model derived from assessments of total body potassium and total body water, body cell mass and extracellular fluid volume increased significantly by 1.6 and 3.0 kg, whereas body fat decreased by 6.1 kg. Results obtained by the bioelectric impedance technique were similar. The mean (+/- SD) concentrations of insulin like growth factor-I increased from 0.26 (0.06) at baseline to 2.56 (1.55) and 2.09 (1.03) kU/L after 6 and 26 weeks of treatment. Calcium and serum phosphate, osteocalcin, and procollagen-III concentrations were significantly higher, and intact PTH concentrations were reduced after 6 and 26 weeks of treatment, respectively. Total and free T3 concentrations were significantly increased after 6 and 26 weeks of treatment, whereas free T4 concentrations were reduced at 6 weeks, but after 26 weeks, free T4 concentrations had returned to pretreatment values. Finally, after 26 weeks of treatment, there was a decrease in the Comprehensive Psychological Rating Scale score (P < 0.05). The results show that GH replacement in GHD adults results in marked alterations in body composition, fat distribution, and bone and mineral metabolism and reduces psychiatric symptoms. Finally, we conclude that the observed beneficial effects of replacement therapy with GH are of sufficient magnitude to consider treatment of GHD adults. PMID- 8432774 TI - A furan fatty acid and indoxyl sulfate are the putative inhibitors of thyroxine hepatocyte transport in uremia. AB - We studied the effects of 3-carboxy-4-methyl-5-propyl-2-furan-propanoic acid (CMPF), indoxyl sulfate, and hippuric acid on iodide production by rat hepatocytes in primary cultures. We questioned whether these substances could explain the alteration of serum thyroid hormone parameters observed in renal failure. Iodide production from [125I]T4 by rat hepatocytes was significantly inhibited in the presence of serum from uremic patients. Serum concentrations of CMPF, indoxyl sulfate, and hippuric acid were markedly elevated in uremic patients. The minimum concentration that inhibited iodide production, when expressed as a molar ratio of the inhibitor to BSA, was 0.13 for CMPF, 0.53 for indoxyl sulfate, and 1.33 for hippuric acid. This molar ratio was lower than the corresponding mean molar ratio in uremic sera for CMPF (0.38) and indoxyl sulfate (0.63), while it was higher than that found for hippuric acid (0.85). The inhibition was reproduced when the inhibitors were added to normal human serum. The decreased iodide production was not due to the inhibition of deiodinase activity. The deiodination of rT3 by rat liver microsomes was unaffected by these inhibitors. Charcoal adsorption of uremic serum normalized the iodide production by hepatocytes. This normalization coincided with almost complete removal of CMPF and indoxyl sulfate, with a concomitant reduction of the free T4 fraction. Dialysis of uremic serum only partially restored iodide production. Even though indoxyl sulfate and hippuric acid were no longer detectable, a high concentration of CMPF remained in the serum. The serum free T4 fraction remained elevated in uremic patients after dialysis. Our studies indicate that CMPF and indoxyl sulfate in concentrations normally present in the serum of uremic patients inhibit cellular transport and subsequent deiodination of T4. These substances may account for the low total T3 level in uremic patients. PMID- 8432775 TI - Impact of sleep on the circadian excursions in the pituitary gonadotropin responsiveness of early follicular phase women. AB - Whereas the nocturnal slowing of the LH pulse frequencies in the early follicular phase (EFP) of the menstrual cycle may be attributed to a sleep-associated increase in opioidergic activity, the concomitant augmentation of LH pulse amplitudes remains unexplained. We reasoned whether alterations in the pituitary gonadotropin responsiveness during the 24-hour rest-activity cycle may account for these enhanced LH pulse amplitudes during sleep. Accordingly, 12 EFP women (cycle days 3-5) were studied on 2 consecutive days during three occasions: a day time between 1000 and 1400 h (day studies), at night between 2200 and 0200 h, while the women were awake (night studies), and finally, during identical night hours, while the women were asleep (sleep studies). At all occasions, blood was collected at 10-min intervals for 4 h, while GnRH (25 micrograms) was administered twice within 2 h. During the day studies, prompt and sustained LH and FSH releases were noted in response to the first and second GnRH stimulations. However, the LH and FSH release after both the first and second GnRH challenges was markedly (P < 0.01) blunted during the night studies. By contrast, this decrease in LH, but not FSH response during the night was completely prevented, when GnRH was administered during sleep. Independent of the time at which GnRH had been administered, the second GnRH stimulations provoked much greater (P < 0.05 or less) LH and FSH releases than the first. Thus, a marked attenuation of the gonadotroph responsiveness is observed in EFP women during the night, and nocturnal sleep may eliminate this decline. Further, the priming actions on the gonadotrophs by repetitive GnRH stimulations are unaffected by the time of GnRH administrations. Collectively, these observations permit us to infer that the increased LH pulse amplitudes observed during sleep in EFP women may not be attributed to increased pituitary responsiveness. PMID- 8432776 TI - The effect of alpha human atrial natriuretic peptide on plasma volume and vascular permeability in normotensive subjects. AB - Low dose infusion of alpha human atrial natriuretic peptide (ANP) has been shown to cause a shift of intravascular fluid to the interstitial space. No studies have been reported on the effect of ANP on capillary permeability to plasma proteins. We studied the effect of low dose ANP (2.5 pmol/kg.min) or equal volume of saline control when infused over 90 min, on plasma volume, transcapillary escape rate of intravascular albumin, and the rate of reentry of albumin to the vascular space in eight normal subjects. Intravenous injection of 125I-human serum albumin was used for measurement of plasma volume and intravascular albumin escape rate. A significant ANP-induced fall in plasma volume (P < 0.01) was observed. Transcapillary escape rate of intravascular albumin when corrected for concurrent plasma volume changes showed a significantly greater escape during ANP infusion than during saline control (P < 0.05). The mean +/- SEM changes in plasma albumin concentration were +0.36 +/- 0.22 g/L.h during ANP infusion and 0.46 +/- 0.50 g/L.h during placebo. Plasma sodium, red cell volume, and urinary albumin and radioactivity remained unchanged. The mass of albumin reentering the circulation per hour showed no significant difference between the 2 days. In summary, low dose ANP infusion in healthy subjects caused a shift of plasma water and electrolytes from the circulation, with albumin escape as a secondary phenomenon. PMID- 8432777 TI - Effect of variations in dietary fat and carbohydrate intake on postprandial lipemia in patients with noninsulin dependent diabetes mellitus. AB - The effect of dietary composition on concentrations of postprandial lipoproteins was studied in eight sulfonylurea-treated patients with noninsulin dependent diabetes mellitus. Two diets were consumed by each patient for 2 weeks in random order, one contained (as percent of total calories) 15% protein, 40% fat, and 45% carbohydrate (CHO), whereas the other consisted of 15% protein, 25% fat, and 60% CHO. At the end of each dietary period, patients were given Vitamin A (60,000 U/m2) with their noon meal, and the concentration of triglyceride (TG) and retinyl esters in plasma and two lipoprotein fractions (Sf > 400 and Sf 20-400) determined over the next 12 h. The results indicated that both postprandial TG and retinyl ester concentrations were higher in plasma (Sf > 400, and Sf 20-400 lipoproteins), when patients ate the 25% fat/60% CHO diet. Thus, replacing saturated fat with CHO accentuates the magnitude of postprandial lipemia. Since TG-rich lipoproteins may be atherogenic, appropriate dietary advice for patients with type 2 diabetes may deserve reappraisal. PMID- 8432778 TI - Endocrine and morphological study of a clinically silent somatotroph adenoma of the human pituitary. AB - Silent somatotroph adenomas are defined as tumors showing morphological features consistent with GH production, but no clinical evidence of GH excess. We report here the case of a 46-yr-old woman with a large pituitary macroadenoma, slightly elevated serum GH levels, high serum insulin-like growth factor-I levels, and abnormal GH dynamics, but no acromegaly. The endocrinological abnormalities receded after transphenoidal surgery despite tumor persistence, as shown by neuroimaging. The reverse hemolytic plaque assay, performed for the first time in a silent GH cell adenoma, demonstrated that the number of GH cells releasing GH and the amount of GH discharged from individual cells were less than those in clinically functioning somatotroph adenomas. Thus, it is conceivable that this tumor secreted only small quantities of GH and for only short periods, providing an explanation for the lack of acromegaly. It appears that silent somatotroph adenomas do not represent a distinct entity. It is more likely that there is a continuous spectrum from clinically functioning, sparsely granulated somatotroph adenomas with high serum GH levels to silent somatotroph adenomas with normal serum GH levels. The cause of the lack of GH oversecretion in silent GH cell adenomas has yet to be elucidated. PMID- 8432779 TI - Multiple hormone deficiencies in children with hemochromatosis. AB - Patients with thalassemia major require multiple blood transfusions leading to hemochromatosis. These patients often have pubertal delay and growth failure, the etiology of which has not been fully elucidated. We performed an extensive endocrine evaluation which included measurements of spontaneous and stimulated levels of gonadotropins, GH, thyroid hormone, and adrenal hormones in 17 patients between the ages of 12 and 18 yr with hemochromatosis receiving desferoxamine therapy. All of the 17 patients had at least one endocrine abnormality, and 12 had more than one abnormality. Abnormalities of the hypothalamic-pituitary gonadal axis were the most common. Six patients had clinical evidence of delayed puberty with spontaneous and stimulated gonadotropin and sex steroid levels appropriate for their delayed pubertal stage. All 14 children in puberty LH pulsatility index below the mean for pubertal stage compared to normal children. Six of the 14 had LH pulsatility index more than 2 SD below the mean for pubertal stage. This may be an indicator of abnormal pituitary function. Six patients failed either the provocative GH tests (peak GH < 7 micrograms/L) or had a mean spontaneous GH less than 1 microgram/L. The 4 patients who failed provocative tests had growth velocities more than 2 SD below the mean for bone age. Three patients had evidence of primary hypothyroidism. We conclude that all patients with hemochromatosis need periodic careful endocrine evaluations because the incidence of endocrine dysfunction is substantial and they may benefit from hormonal therapy. PMID- 8432780 TI - Maturation of gonadotropin and sex steroid responses to gonadotropin-releasing hormone agonist in males. AB - We have previously demonstrated that a single dose of the GnRH agonist nafarelin stimulates both gonadotropin and sex steroid secretion in adult men and women. In order to define the maturational steps involved in this response, we tested the effect of nafarelin on LH, FSH, testosterone (T), and estradiol (E2) secretion over 24 h in four groups of males: prepubertal (P1; n = 4), early pubertal (P2; n = 8), and midpubertal boys (P3; n = 4) with variations in the timing of puberty, and normal young adult males (P4; n = 10). Nafarelin stimulated rapid gonadotropin release in all groups, but the pattern of LH response varied. In prepubertal and pubertal boys, LH levels peaked 3-4 h after nafarelin and declined by 50% or more at 24 h post nafarelin. By contrast, adults reached an initial LH peak at 1 h, and LH secretion was sustained with levels 24 h post nafarelin equivalent to those during the early response phase. Nafarelin stimulated T secretion in all groups, but the response was greatest in groups P3 and P4; the maximal incremental rise (delta) in T was 1.2 +/- 0.5, 4.4 +/- 1.0, 18.8 +/- 5.4, and 15.3 +/- 1.4 nmol/L in P1, P2, P3, and P4 males, respectively (analysis of variance: F = 14.4, P < 0.001). E2 concentrations increased much more in adults than in the other groups post nafarelin: delta E2 was 5.5 +/- 1.1, 22.1 +/- 14.7, 83.9 +/- 47.5, and 323.8 +/- 14.7 pmol/L in the P1, P2, P3, and P4 groups, respectively (F = 71.1, P < 0.001). Similarly, the delta E2/delta T ratio was significantly greater in adult males than in less mature males. This developmental pattern of response to nafarelin suggests that male pubertal maturation involves increase of the gonadotrope LH readily releasable and reserve pools. The dissociation of E2 from T responses to nafarelin during puberty suggests that aromatase activity does not fully mature in males until puberty is complete. These findings indicate that a single dose of the GnRH agonist nafarelin is a promising means of assessing the maturation of the pituitary gonadal axis in males. PMID- 8432781 TI - Pyridostigmine potentiates growth hormone (GH)-releasing hormone-induced GH release in both men and women. AB - It has been recently reported that pyridostigmine (PD), an indirect cholinergic agonist, probably acting via inhibition of hypothalamic somatostatin, potentiates the GH-releasing hormone (GHRH)-induced GH rise in men, but not in women. The aim of this study was to verify the sex-related, if any, GH response to GHRH (1 microgram/kg, i.v., as a bolus) both alone and preceded by two different doses of PD (120 mg, group A, and 60 mg, group B, given orally 60 min before GHRH) in a large group of volunteers (36 women, aged 18-35 yr, and 48 men, aged 18-35 yrs). In group A, 120 mg oral PD potentiated the GH response to GHRH in both men [area under the curve (AUC), 2579.3 +/- 264.5 vs. 806.2 +/- 99.7 micrograms/L.h; P < 0.00001] and women (AUC, 2273.2 +/- 248.7 vs. 792.6 +/- 72.7 micrograms/L.h; P < 0.00001). Similarly, in the group B, 60 mg oral PD potentiated the GH response to GHRH in both men (AUC, 1929.6 +/- 157.2 vs. 568.2 +/- 81.3 micrograms/L.h; P < 0.01) and in women (AUC, 1655.9 +/- 146.9 vs. 738.2 +/- 105.7 micrograms/L.h; P < 0.01). The GH responses to GHRH, both alone and after 120 and 60 mg oral PD, did not significantly differ in men and women. No sex-related difference was observed in the cholinergic side-effects (mild abdominal pain and muscle fasciculations) that occurred in nearly 30% of the subjects. In conclusion, our results clearly show that there is no sex-related difference in the potentiating effect of PD on GHRH-induced GH release, ruling out the suggestion that women have increased cholinergic activity, leading to reduced somatostatinergic tone. PMID- 8432782 TI - Predominance of stimulatory effects of interleukin-1 beta on isolated human pancreatic islets. AB - The aim of the present study was to characterize the effects of human recombinant interleukin-1 beta (rIL-1 beta) on human pancreatic islets. For this purpose, islets isolated from adult cadaveric donors were exposed to rIL-1 beta (1 or 3 ng/mL) for different periods of time. In some experiments, rat pancreatic islets were exposed in parallel to the cytokine. After 48 h of culture in the presence of rIL-1 beta, the human islets showed an increased insulin release during short term incubations in the presence of 1.7 or 16.7 mM glucose. There was also a 3- to 4-fold increase in insulin accumulation into the culture medium, but rIL-1 beta did not affect human islet glucose metabolism. These stimulatory effects of rIL-1 beta on human islets were already present after an acute (2-h) exposure to the cytokine, and this functional stimulation was blocked by an IL-1 receptor antagonist protein. After exposure of human islets to rIL-1 beta for 6 days, there was no effect of the cytokine on either glucose metabolism or insulin release compared to those in control islets. Rat islets exposed for 48 h in culture to the same concentrations of rIL-1 beta, however, showed a 40-60% decrease in insulin accumulation into the medium, glucose-induced insulin release, and glucose oxidation. Moreover, while there was no effect of rIL-1 beta on nitrite production by human islets, there was a 7- to 11-fold increase in nitrite production by rat islets. Nitrite is an end product of the highly reactive radical nitric oxide (NO), and there are data to suggest that NO is an important mediator of the suppressive and cytotoxic actions of IL-1 on rat islets. The present observations suggest that human islets are less sensitive to the inhibitory effects of human rIL-1 beta than rat islets, and that this is due to a lack of induction of NO synthesis by the cytokine in human islet cells. PMID- 8432783 TI - Inflammatory mediators regulate interleukin-8 production by cultured gestational tissues: evidence for a cytokine network at the chorio-decidual interface. AB - The physiology of parturition, and the pathophysiology of preterm labor, is incompletely understood. Infection of gestational tissues may account for a significant proportion of women who experience preterm labor. Interleukin-8 (IL 8), or neutrophil-activating protein (NAP-1), is a potent chemotactic and activating factor for neutrophils and has been implicated in the pathogenesis of inflammatory injury to skin and lung, but has yet to be described in gestational tissues. Cultured chorion and decidual cells obtained from normal human pregnancies were used to evaluate whether these tissues produce IL-8 basally and in response to inflammatory cytokines. As measured by specific IL-8 RIA, chorion and decidual cells produce IL-8 constitutively and in response to IL-1 beta and tumor necrosis factor. Cotreatment of chorion cells or decidual cells with IL-1 beta and actinomycin D or cycloheximide abrogated IL-8 production. Northern blot analysis confirmed that IL-1 beta stimulation of chorion and decidual cells resulted in increased IL-8 messenger RNA expression. Our data support the concept that a complex cytokine network between maternal and fetal gestational tissues exists, and that activation of inflammatory cytokine production in these tissues, including IL-8, likely contributes to the pathophysiology of infection-induced preterm labor. PMID- 8432784 TI - Percutaneous ultrasound-guided ethanol injection: a new treatment of toxic autonomously functioning thyroid nodules? AB - Twenty autonomously functioning thyroid nodules were treated with ultrasound guided percutaneous ethanol injection (PEI) and followed for 12 months. PEI was performed on symptomatic and biochemically proven thyrotoxic patients by injecting 2.0-4.0 mL sterile ethanol and was repeated 3-8 times, depending on nodule size. Serum thyroglobulin increased immediately after PEI, peaked at 6-10 h, and declined thereafter. Free T4 progressed slowly during the first 24 h. Free T3 showed a delayed and not significant increase. By the end of the treatment (4 weeks), PEI had produced clinical improvement and hormonal normalization. Three months later, serum TSH was detectable and responsive to TRH in 17 of the 20 patients. All nodules had a significant shrinkage at ultrasound evaluation. The previous hot thyroid areas manifested hypofunction at technetium-99 m pertechnetate scintiscan, and the surrounding parenchyma returned to normal function in all but the 3 cases with still suppressed TSH. The histological features of a nodule that had been operated upon and the fine needle aspiration biopsy patterns obtained after PEI showed coagulative necrosis, with scanty follicles, some fibroblasts, but no lymphocytic infiltration. The procedure was generally well tolerated, but in 1 case it induced temporary dysphonia, and in another patient, it caused a transient exacerbation of thyrotoxicosis. PMID- 8432785 TI - Protein kinase-C stimulatory activity in human amnion cytosol. AB - Cytosolic preparations from human amnions at term were tested for the presence of endogenous modulators of protein kinase-C (PKC) activity. Tissues were obtained from 14 patients undergoing cesarean section (CS) and 14 patients after spontaneous delivery (SL). PKC activity was significantly greater in cytosols from CS than SL amnion (1.65 +/- 0.04 vs 0.73 +/- 0.2 pmol/min, respectively; mean +/- SE; n = 14 CS; n = 14 SL; P < 0.05). When amnion cytosols were mixed with a control preparation of PKC (rat brain cytosol partially purified on diethylaminoethyl), PKC activity was significantly increased compared to the control value (control, 12.81 +/- 2.1; control + CS, 22.19 +/- 1.5; control + SL, 21.98 +/- 0.7 pmol/min). The stimulation of PKC was dose dependent. The PKC stimulatory factor in amnion cytosol was stable to heat treatment at 80-90 C for 2 min (control + heat-treated CS, 23.20 +/- 1.2; control + heat-treated SL, 24.49 +/- 1.0 pmol/min) and substituted for phosphatidylserine and diacylglycerol in the PKC assay (control, no lipids, 0.05 +/- 0.04 pmol/min; control + amnion cytosol, no lipids, 9.60 +/- 1.06 pmol/min). The PKC stimulatory factor was calcium dependent, was not extractable in organic solvents, and was greater then 100,000 mol wt. Thus, the human amnion contains a PKC stimulatory factor which may modify or mediate the cellular response to extracellular stimulators of the PKC pathway. PMID- 8432786 TI - Comparison of plasma androgen glucuronide levels after percutaneous or peroral androgen treatment in men: evidence for important splanchnic contribution to plasma 17 beta-hydroxyandrogen glucuronides. AB - To investigate whether glucuronides of 17 beta-hydroxyandrogens are formed mainly in peripheral tissues or in splanchnic tissues, we compared androstanediol (AD) glucuronide (ADG) and dihydrotestosterone (DHT) glucuronide (DHTG) levels as well as the ratios of glucuronides over free steroids after transcutaneous DHT gel administration to levels and ratios found after oral administration of testosterone undecanoate. Whereas DHT and AD plasma levels were much higher after transcutaneous DHT gel administration, ADG and DHTG levels as well as glucuronide/free androgen ratios were an order of a magnitude higher after oral TU. This indicates that 17 beta-hydroxyandrogen glucuronides cannot be considered specific metabolites of androgen target tissues and are formed to a large extent in the splanchnic circulation. PMID- 8432787 TI - Serum bioactive gonadotropins during male puberty: a longitudinal study. AB - To evaluate the relative changes in serum bioactive (B) and immunoreactive (I) plasma gonadotropin concentrations during pubertal maturation, 28 healthy boys were enrolled at Tanner stage I and followed at 6-month intervals until achievement of Tanner stage V of pubertal maturation. At each visit, a careful interview, complete physical examination, sexual maturation staging, and bone age x-ray study were done, and a blood sample was obtained. Serum concentrations of PRL, dehydroepiandrosterone, and its sulfate, delta 4-androstenedione, estrone, estradiol, and testosterone (T) were determined by RIA. Samples from 20 boys were assayed for I-LH by RIA and for B-LH by the rat interstitial cell testosterone production assay, using 2 standards [Second International Reference Preparation Human Menopausal Gonadotropin (2nd IRP-hMG) and LER 960]. Samples from 11 boys (3 from LH group and 8 others) were assayed for I-FSH by RIA and B-FSH by the rat Sertoli cell aromatase induction assay. The results were analyzed by regression analysis for B and I LH and FSH by Tanner stages of puberty, and by correlation of B to I LH and FSH as well as B and I LH and FSH to T. The results from both LH standards correlated well to each other (r = 0.967 and 0.882 for B- and I-LH, respectively), and the data are presented for 2nd IRP-hMG standard. In both groups of boys serum T concentrations increased progressively with pubertal development (P < 0.001). The boys bone age, testicular volume, serum T, dehydroepiandrosterone sulfate, dehydroepiandrosterone, delta 4-androstenedione, estrone concentrations correlated well with pubertal maturation, similar to previously published data and indicate that this group of boys had progressed through puberty in the expected normal manner. Mean serum I-LH concentrations increased progressively from Tanner stage I to V of puberty (P < 0.001), and serum B-LH exceeded the increase in serum I-LH levels. Mean serum I-LH concentrations were 2.0 +/- 0.1, 2.9 +/- 0.2, 4.7 +/- 0.4, 6.7 +/- 0.7, and 10.4 +/- 2.0 IU/L 2nd IRP-hMG whereas mean serum B-LH concentrations were 0.8 +/- 0.1, 2.2 +/- 0.2, 5.9 +/- 0.2, 10.3 +/- 1.2, and 22.3 +/- 3.8 IU/L 2nd IRP-hMG for Tanner stages I-V of puberty, respectively. This resulted in a progressive increase of LH B/I ratio with advancing pubertal maturation (P < 0.001).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8432788 TI - Augmented induction by dexamethasone of metallothionein IIa messenger ribonucleic acid in fibroblasts from a patient with cortisol hyperreactive syndrome. AB - Northern blot analysis was used to investigate the effect of dexamethasone (Dex) or zinc on messenger RNA (mRNA) levels of metallothionein-IIa (MT-IIa) in fibroblasts from a patient with cortisol hyperreactive syndrome and from three normal subjects. Dex was seen to increase MT-IIa mRNA levels and brought them to a maximum after 12 h. Zinc also increased the levels of MT-IIa mRNA and brought them to a maximum at 8 h after the addition. Dex as well as zinc caused a dose related increase in MT-IIa mRNA levels. Dex had a maximal inductive effect on MT IIa at a concentration of 10(-6) mol/L and zinc at a concentration of 10(-4) mol/L. There was no significant difference in the levels of basal expression of the MT-IIa gene between the patient's and normal fibroblasts. But in three separate experiments induction of MT-IIa gene by Dex obtained for the patient's fibroblasts was almost twice as much as that for normal fibroblasts. On the other hand, there were no significant difference in induction by zinc between the patient's and normal fibroblasts. These data indicated that the patient's cells were hyperreactive to glucocorticoids as seen from the effect of Dex on the MT IIa mRNA levels. PMID- 8432789 TI - Elevated 1,25-dihydroxyvitamin D levels in patients with chronic obstructive pulmonary disease treated with prednisone. AB - Glucocorticoid administration is a well established cause of osteopenia. Mechanisms underlying the deleterious effect of glucocorticoids on bone may include direct inhibition of bone formation as well as indirect effects through changes in intestinal calcium absorption, renal calcium excretion, and/or levels of the calciotropic hormones. To further examine the potential role of the calciotropic hormones we measured serum levels of PTH and 1,25 dihydroxyvitamin D [1,25(OH)2D], as well as serum and urine levels of calcium and vertebral bone density in patients with chronic obstructive pulmonary disease being managed with or without prednisone. Patients treated with prednisone had lower spinal bone density (53 vs. 106 mg/cm3) and higher serum calcium (2.40 vs. 2.33 mmol/l), urine calcium (6.9 vs. 2.7 mmol/24h), and 1,25(OH)2D levels (147 vs. 95 pmol/L). Compared to the patients not treated with glucocorticoids. PTH levels also tended to be higher (33 vs. 26 microliters-eq/ml), but the difference was not significant. Serum and urine calcium levels correlated positively with 1,25(OH)2D levels, but none of these measurements correlated with PTH levels. Our results suggest that prednisone treatment alters the regulation of 1,25(OH)2D production, and this may contribute to the loss of bone mineral induced by prednisone. PMID- 8432790 TI - Influence of plasma glucose rate of decrease on hierarchy of responses to hypoglycemia. AB - To test the hypothesis that the rate of decrease in plasma glucose concentration may affect the hierarchy of responses to hypoglycemia, we compared plasma couterregulatory hormone concentrations, autonomic and neuroglycopenic symptom scores, and cognitive function test performance in 10 normal volunteers whose plasma glucose concentration was either rapidly (over 30 min) decreased to 3.7 mmol (66 mg/dL) or was slowly decreased in a stepwise manner to plateaus of 4.3 mmol (78 mg/dL), 3.7 mmol (66 mg/dL), 3.0 mmol (54 mg/dL), and 2.3 mmol (42 mg/dL). Comparable plasma counterregulatory hormone concentrations and autonomic symptom scores were observed in both sets of experiments during the 3.7 mmol (66 mg/dL) plateaus. In the stepwise decrement experiments, significant increases in neuroglycopenic symptom scores and deterioration in cognitive performance occurred only during the last glycemic plateau (2.3 mmol, 42 mg/dL). In the rapid decrement experiments, no increase in neuroglycopenic symptom score or deterioration in cognitive performance was observed during the 3.7 mmol (66 mg/dL) plateau. We, therefore, conclude that in normal volunteers the rate of decrease in plasma glucose concentration does not affect the hierarchy of responses to hypoglycemia. PMID- 8432791 TI - Iodine-induced hypothyroidism: a clinical and histological study of 28 patients. AB - Thirty-three thyroid specimens obtained from 28 patients with clinically and laboratory-proven iodine-induced hypothyroidism were examined clinically, histologically, immunohistochemically, and ultrastructurally. Twenty-eight specimens obtained during the hypothyroid phase showed common histological changes in the thyroid thought to be specific for this disease; hyperplastic change in the follicles with some papillary folding, cuboidal to columnar change of follicular cells with clear and vesicular cytoplasm, scanty or absent colloid material in the large distended follicles, and occasional dilatation of capillary vessels. Lymphocytic infiltration was present in about half of the specimens. No specimens showed either stromal fibrosis or parenchymal atrophy. Immunohistochemical and electron microscopic examination revealed that severe interference with thyroid hormone biosynthesis occurs in the follicular cells. In two patients who had a follow-up biopsy in the recovery (euthyroid) phase after iodine restriction, the histological involvement seen in the hypothyroid phase was no longer present. The histological changes in the thyroid gland seen in patients with iodine-induced hypothyroidism are characteristic. This disease can be diagnosed from laboratory tests, but thyroid biopsy is also a useful tool to differentiate this condition from other diseases causing hypothyroidism. Not only clinicians, but also pathologists, must pay attention to this type of hypothyroidism, because thyroid function may revert to normal by iodine restriction alone. PMID- 8432792 TI - Hormone replacement therapy alters insulin sensitivity in young women with premature ovarian failure. AB - In this study, we report the effects of cyclic hormone replacement therapy on carbohydrate metabolism in six women with premature ovarian failure. Using tolbutamide-modified iv glucose tolerance tests patients were evaluated during three different intervals of their second treatment cycle: no hormone replacement, estradiol-only (E2-only) replacement, and E2-plus medroxyprogesterone acetate (MPA) replacement. Insulin sensitivity and glucose effectiveness were derived using insulin and glucose levels obtained from tolbutamide-modified iv glucose tolerance tests and analyzed with the minimal model computer program. The mean insulin sensitivity (x 10(-4)/min/microU.ml) significantly decreased from 4.0 +/- 0.8 during no hormone replacement and 3.8 +/ 0.8 during E2-only replacement to 2.6 +/- 0.5 (x 10(-4)/min/microU/ml) during E2 plus-MPA replacement (P < 0.005). Glucose effectiveness did not change as a function of the phase of hormone replacement therapy. These findings indicate a significant decrease in sensitivity to insulin associated with MPA treatment but no observable change in insulin sensitivity during the E2-only phase of cyclic steroid replacement therapy in young women. Our results support the hypothesis that impairment of insulin-mediated glucose uptake during the luteal phase of the menstrual cycle is due to increased progesterone secretion. PMID- 8432793 TI - Multiple molecular weight forms of immunoreactive alpha-inhibin in human seminal plasma. AB - The purpose of these studies was to determine whether the total immunoreactive alpha-inhibin protein concentration in seminal plasma correlated with serum gonadotropin levels or semen characteristics and to identify the forms of alpha inhibin present in seminal plasma. Thirty-eight serum samples from men being evaluated for infertility were selected for study based on their serum hormone profiles and semen parameters. Serum LH and testosterone levels were normal, but FSH levels ranged from normal to hypergonadotropic (> 20 IU/L). Most semen parameters were within normal ranges, but germ cell numbers ranged from normal to azoospermic. Thus, seminal plasma from these men provided a unique opportunity to examine the antigenic forms of alpha-inhibin in individuals in whom strong correlations between inhibin and FSH levels might be predicted because of the observed ranges of FSH levels and germ cell numbers. Seminal plasma alpha-inhibin was characterized by RIA or Western blotting, using an antiserum directed against the N-terminal of the alpha-subunit of mature [32,000 mol wt (M(r))] inhibin. The antiserum recognized the alpha-subunit of dimeric inhibin as well as free alpha inhibin and alpha-inhibin precursor proteins. Total immunoreactive alpha-inhibin ranged from 8.21-43.99 nmol/L in seminal plasma. However, alpha-inhibin levels were not statistically correlated with serum FSH levels or any of the measured semen parameters (including germ cell number). In contrast, the immunoreactive alpha-inhibin concentration in seminal plasma was negatively correlated (P < 0.01) with the serum LH level. Western blot analyses revealed that multiple forms of immunoreactive alpha-inhibin are present in seminal plasma. The majority of immunoreactivity was associated with monomeric proteins (ranging from 58,000 95,000 M(r)) that were larger than the alpha-subunit (21,000 M(r)) predicted for mature dimeric human inhibin (32,000 M(r)). The relative amounts of individual forms of immunoreactive alpha-inhibin varied among the patients studied, but could not be correlated with other serum or seminal parameters measured. Our observations demonstrate that various monomeric alpha-inhibin proteins are present in human seminal plasma. It is unlikely that these proteins alone or combined with inhibin beta-subunit proteins have identical biological activities. Thus, until assays specific for each of the various forms of immunoreactive alpha inhibin are developed, their role as well as that of inhibin in the endocrine or local modulation of testicular function cannot be deduced from RIA data alone. PMID- 8432794 TI - Long term therapy of patients with macroprolactinoma using repeatable injectable bromocriptine. AB - The efficacy and tolerability of a long term treatment (21-53 months; mean, 36) with a new injectable form of bromocriptine (Parlodel LAR, Sandoz) was assessed in 13 patients (9 males and 4 females, aged 14-68 yr) with macroprolactinoma. Parlodel LAR was administered deeply im once monthly, with 50 mg as the first dose. Depending on the patient's tolerability to the drug and the PRL levels, the dose was individually progressively increased to 100 mg (2 patients), 150 mg (3 patients), or 250 mg (4 patients). Persistently normal PRL levels were recorded in 4 patients even after the first injection and in 5 other patients treated with higher doses of Parlodel LAR (2 patients with 100 mg/month; 3 patients with 150 mg/month). The remaining 4 patients who were treated with 250 mg/month had a marked reduction of PRL levels (72-94%), but did not reach normalization. Two patients treated with 150 mg/month maintained normoprolactinemia in spite of subsequent dose reduction of Parlodel LAR to 50-100 mg/month. In 1 patient PRL plasma concentrations remained within normal range for 3 months after the transitory discontinuation of Parlodel LAR at the end of the first year of therapy. Regular menses were resumed in 1 of 3, and galactorrhea disappeared in 2 of 3 women. All male patients had a return of libido and potency; gynecomastia disappeared in both male patients, and galactorrhea disappeared in 1 of 2 male patients. Visual fields improved in all 5 patients; complete normalization occurred in 2 of them. A consistent shrinkage of the macroadenoma (23-100%) at different times after therapy was shown by magnetic resonance imaging and/or computed tomography in 12 of 13 patients. Six patients reported mild/moderate side-effects (nausea, vomiting, orthostatic hypotension, or dizziness) within 24 h after the first injection. In 2 of these patients, mild side-effects persisted for 1-2 days after the first 3-6 injections, and in one patient, mild nausea was reported after each injection. In conclusion, in patients with macroprolactinoma, Parlodel LAR is an effective and well tolerated preparation of bromocriptine when administered once a month. PMID- 8432795 TI - Reduced postprandial cholecystokinin (CCK) secretion in patients with noninsulin dependent diabetes mellitus: evidence for a role for CCK in regulating postprandial hyperglycemia. AB - The plasma cholecystokinin (CCK) response to a test meal was studied in 16 control subjects and 15 patients with noninsulin-dependent diabetes mellitus (NIDDM). Basal CCK levels were approximately 1 pmol in both groups. However, after the test meal, plasma CCK levels were 2-fold greater in the controls when compared to the diabetics. In controls, CCK levels maximally increased by 5.6 +/- 0.8 pmol (mean +/- SEM) 10 min after feeding, whereas in the NIDDM patients this value was 1.9 +/- 0.6 pmol (P < 0.001). After the test meal, the normal subjects showed no postprandial rise in blood glucose, whereas the diabetic patient showed a rise of 2.6 +/- 0.7 mmol. To determine whether the decreased CCK levels may have been related to the postprandial hyperglycemia, 7 diabetic subjects were infused with CCK. With this CCK infusion, postprandial glucose levels did not rise. These data suggest, therefore: 1) a role for cholecystokinin in regulating postprandial hyperglycemia in man, 2) abnormalities in CCK secretion occur in NIDDM and may contribute to the hyperglycemia seen in this disease. PMID- 8432796 TI - Thyrotropin (TSH)-releasing hormone stimulation test responses employing third and fourth generation TSH assays. AB - TRH stimulation tests (n = 1109) were performed on 1061 ambulatory and 43 hospitalized patients with varying thyroid status, using a TSH immunochemiluminometric assay with third and fourth generation sensitivity characteristics (functional sensitivity, 0.01 and 0.001 mU/L, respectively). TRH test results were analyzed as both absolute (stimulated minus basal TSH) and fold (stimulated/basal TSH) responses. The absolute TRH response varied 8-fold across the physiological TSH range, whereas the mean fold response remained almost constant (mean +/- SEM, 8.5 +/- 0.2). The fold response became progressively attenuated as basal TSH values declined below physiological levels, becoming essentially absent in clinically thyrotoxic patients with markedly depressed basal serum TSH levels (0.007 +/- 0.002 mU/L). Progressive attenuation also occurred at hypothyroid TSH levels; a markedly impaired fold response (2.5 +/- 0.4) was characteristic of primary hypothyroid patients with basal TSH values greater than 50 mU/L. In untreated central hypothyroid patients with near-normal basal TSH levels, the TRH fold response was impaired (1.7 +/- 0.2), whereas in T4 replaced central hypothyroid patients, fold responses were near normal (5.6 +/- 1.2). Neither nonthyroidal illness, age, or sex appeared to influence the pattern of fold TRH response in the populations evaluated. When using third and fourth generation TSH methodology, the TRH-stimulated TSH fold response is more diagnostically useful than the absolute TRH response. However, if patients have an intact hypothalamic-pituitary axis, there appears to be no diagnostic advantage gained by TRH testing over an accurately measured basal TSH value. PMID- 8432797 TI - Regression of uterine leiomyomata in response to the antiprogesterone RU 486. AB - Uterine leiomyomata are steroid hormone dependent tumors which possess receptors for estrogen (ER) and progesterone (PR). We reasoned that an antiprogesterone (RU 486) may induce regression of leiomyomata by withdrawal of progesterone action and/or by its interference of estrogen action. Accordingly, we examined the effects of daily administration of RU 486 (50 mg) for a period of 3 months in 10 patients with uterine leiomyomata and regular menstrual cycles. Baseline ultrasound examinations were obtained and repeated monthly during treatment as a measure of leiomyomata volume. Hormonal parameters were monitored by blood samples obtained prior to treatment and daily for 7 days, weekly for 4 weeks and monthly for the duration of therapy. Myomectomy or hysterectomy was performed in 6 of 10 patients at the end of treatment. Leiomyomata and myometrial tissue was obtained for immunocytochemical analysis of ER and PR protein. Amenorrhea was induced in all patients during treatment. Leiomyomata volume (mean +/- SE) decreased 21.9 +/- 4.8% after 4 weeks, 39.5 +/- 6.6% (P < 0.001) after 8 weeks, and 49.0 +/- 9.2% (P < 0.001) after 12 weeks of treatment compared to pretreatment measurements. Serum LH levels (P < 0.005), but not FSH levels, more than doubled during the first 3 weeks of treatment with a concomitant increase in serum androstenedione (P < 0.006) and testosterone (P < 0.0001) levels. These elevated hormonal levels returned to baseline at 4 weeks without further changes during the remainder of treatment. A significant rise in serum dehydroepiandrosterone sulfate (P < 0.0001) and cortisol (P < 0.01) was seen at 12 weeks, suggesting an antiglucocorticoid effect of RU 486 has occurred. Serum estradiol, estrone, progesterone, sex hormone binding protein, thyroid stimulating hormone, and PRL were unchanged from early follicular phase values. PR but not ER immunoreactivity was significantly reduced in both leiomyomata and myometrium after RU 486 treatment compared with tissues from untreated patients, suggesting that regression of tumors may be attained through a direct antiprogesterone effect. However, an alteration in ER functionality cannot be excluded. We conclude that RU 486 is well tolerated, safe, and effective; thus, it may prove to be a novel mode of management for uterine leiomyomata. PMID- 8432798 TI - Regulation of plasminogen activator inhibitor-1 and -2 messenger ribonucleic acid levels in human cumulus and granulosa-luteal cells. AB - Plasminogen activators and their inhibitors have been implicated in the process of fibrinolysis, tissue remodeling, and ovulation. Epidermal growth factor (EGF), a paracrine hormone found in the human ovary, increases plasminogen activator (PA) activity and the gene expression of PA and plasminogen activator inhibitor (PAI) in human endothelial cells and human cell lines. Gonadotropins also increase PA activity and gene expression in rat preovulatory granulosa cells. We have now analyzed the gene expression of PAI-1 and PAI-2 in uncultured human cumulus cells (CC), uncultured granulosa-luteal cells (GLC), and cultured GLC obtained from preovulatory follicles of patients undergoing assisted reproductive technologies. We also studied the effects of hCG and EGF on PAI-1 and PAI-2 mRNA levels in cultured GLC; GLC were cultured in serum-free medium for various times within 24 h with or without hCG and for 6 h with or without hCG, EGF, or EGF plus hCG. Total RNAs from CC and GLC were extracted, and blot hybridizations with 32P labeled PAI-1, PAI-2, or 28S ribosomal RNA cDNA probes were performed. Both CC and GLC expressed PAI-1 and PAI-2 genes. In GLC, steady state levels of PAI-1 mRNA levels steadily increased within 24 h of culture, whereas PAI-2 levels peaked at 6 h of culture. PAI-1 mRNA levels were not affected by hCG or EGF at 6 h of culture, but PAI-2 mRNA levels were significantly increased by EGF at 6 h of culture. These studies demonstrate that human GLC PAI-1 and PAI-2 mRNA levels are differentially regulated and suggest that EGF may be involved in modulation of the human ovarian PA system during the periovulatory period. PMID- 8432799 TI - Thyrotropin-secreting pituitary carcinoma. AB - Pituitary tumors rarely metastasize outside the central nervous system. Of the more than 100 reported TSH-secreting adenomas, we now describe the first carcinoma. A 40-yr-old woman had transsphenoidal surgery for a large TSH secreting pituitary adenoma in 1984. She had increased thyroid hormone levels with a TSH that varied from 16-31 microU/mL, and an unusually high alpha-subunit that ranged from 125-150 ng/mL. Because of residual tumor, she had a left craniotomy in 1985 followed by radiation. Despite these therapies, she had a residual tumor that remained stable until January 1989 when her tumor nearly doubled in size. She received radiation therapy and octreotide with marked diminution of the tumor and clinical improvement. In August 1989, she presented with leg weakness, and magnetic resonance imaging revealed a large sacral mass. A biopsy confirmed that the sacral mass was a metastasis from the pituitary tumor. Due to additional metastases in the lung, she received 5-fluorouracil, cytoxan, and adriamycin, with marked decrease in her lesions. Further substantiation of the metastatic pituitary tumor was made when the patient returned in December 1989 with a pleural effusion containing pituitary tumor cells. Of all the reported cases of TSH-secreting adenomas, this case had the highest alpha-subunit portending future metastases. Furthermore, the apparent response to octreotide and response to chemotherapy are encouraging and suggest that new therapies should be explored. Finally, since TSH-secreting adenomas tend to be more invasive than other pituitary tumors, this case underscores the need for early diagnosis and aggressive treatment of these tumors. PMID- 8432800 TI - Molecular epidemiology of plasmid spread among extended broad-spectrum beta lactamase-producing Klebsiella pneumoniae isolates in a pediatric hospital. AB - Over a 12-month period, 43 children in eight different wards of our hospital (Hopital Robert Debre) were infected or colonized with Klebsiella pneumoniae strains producing extended broad-spectrum beta-lactamases. The epidemiology of the outbreak was studied by a molecular approach including the determination of the beta-lactamase physicochemical parameters and plasmid profiles, as well as analysis of the restriction fragment length polymorphisms of the rDNA regions (ribotyping). The last approach produced 12 and 5 different patterns with EcoRI and HindIII, respectively, thus identifying 15 different ribotypes among the 43 clinical K. pneumoniae strains. However, 60% of the strains in six wards belonged to only two ribotypes, whereas nine ribotypes were observed only once. Twelve isolates from different wards that were representative of the eight most common ribotypes showed four different beta-lactamase isoelectric focusing patterns and seven different plasmid profiles by direct analysis or after EcoRI digestion. Thus, at least two genetically unrelated strains in the same ward were found to have the same plasmid content. Our results show the complexity of the outbreak, which was associated with patient-to-patient cross-contamination with several epidemic strains with different plasmid contents, interspersed sporadic cases with nonepidemic strains, and the possible spread of a plasmid. The combination of plasmid profile analysis and ribotyping therefore seems to be powerful at deciphering the details of such outbreaks. PMID- 8432801 TI - Identification of clinical yeast isolates by using the Microring YT. AB - The Microring YT (MYT; Medical Wire & Equipment Co., Victory Gardens, N.J.) is a system for the rapid (24 to 48 h) identification of yeasts. The MYT system was evaluated and compared with the API20C (Analytab Products, Plainview, N.Y.) system for its ability to identify 677 clinical yeast isolates. Only 458 isolates (68%) were correctly identified by the MYT system, and the accuracy of the system varied considerably (0 to 96%), depending on the species. While MYT was less expensive and convenient to use and results were available 24 h sooner, it is inadequate for identification of many commonly isolated yeasts and is not designed for the identification of Cryptococcus species. PMID- 8432802 TI - Cryptosporidiosis: multiattribute evaluation of six diagnostic methods. AB - Six diagnostic methods (Giemsa staining, Ziehl-Neelsen staining, auramine rhodamine staining, Sheather's sugar flotation, an indirect immunofluorescence procedure, and a modified concentration-sugar flotation method) for the detection of Cryptosporidium spp. in stool specimens were compared on the following attributes: diagnostic yield, cost to perform each test, ease of handling, and ability to process large numbers of specimens for screening purposes by batching. A rank ordering from least desirable to most desirable was then established for each method by using the study attributes. The process of decision analysis with respect to the laboratory diagnosis of cryptosporidiosis is discussed through the application of multiattribute utility theory to the rank ordering of the study criteria. Within a specific health care setting, a diagnostic facility will be able to calculate its own utility scores for our study attributes. Multiattribute evaluation and analysis are potentially powerful tools in the allocation of resources in the laboratory. PMID- 8432803 TI - Detection of the pathogenic parasite Toxoplasma gondii by specific amplification of ribosomal sequences using comultiplex polymerase chain reaction. AB - Amplification of DNA sequences from ribosomal DNA (rDNA) was tested as a specific and sensitive method for the detection of small numbers of Toxoplasma gondii tachyzoite cells. We applied the polymerase chain reaction (PCR) on the basis of detection of the 110-fold repetitive rDNA as a target by using (i) DNA sequences within the small ribosomal subunit known to be universal and conserved in all eukaryotes and (ii) small ribosomal subunit and intergenic spacer rDNA sequences known to be T. gondii species specific. The level of sensitivity obtained from a crude cell lysate allowed the detection of as few as one parasite visualized directly as a specific PCR product in agarose gels. By using a combination of universal and T. gondii species-specific primers, we propose a comultiplex-based PCR approach as a new diagnostic tool. The combination of sensitivity, specificity, and built-in positive and negative PCR controls should make detection of the rDNA sequences by comultiplex PCR a useful clinical test for the diagnosis of toxoplasmosis and for epidemiological studies. Finally, the idea of a built-in positive control to support or counter the T. gondii-specific PCR result is novel and is a notable advance. PMID- 8432804 TI - Comparison of polymerase chain reaction with culture and serology for diagnosis of murine experimental Lyme borreliosis. AB - After the intradermal inoculation of mice with Borrelia burgdorferi, the antibody response, culture, and histology of blood and target organs were assessed and compared with results of a nested polymerase chain reaction (PCR) assay. Of 247 specimens of heart, brain, bladder, and blood, the tested concordance between the PCR and culture was 72%. In the 69 instances of discordance, the PCR was positive in 51 and the culture was positive in 18; thus, the PCR was concordant or more sensitive in 93% of the tested organs. In mice infected with 10 spirochetes, serology confirmed by Western blotting (immunoblotting) was more sensitive than either culture or PCR of brain, bladder, or heart specimens. The organs most commonly culture or PCR positive were the heart and bladder; the brain was infected in only 26% of the animals. DNA hybridization was helpful in confirming the PCR product as being specific and, in some cases, in demonstrating a positive product in the face of negative agarose gels. PCR was less sensitive than culture in detecting the presence of spirochetes in blood specimens, possibly because of the presence of blood inhibitors. We thus found a nested PCR assay, using primers from a genomic sequence, to be a valuable adjunct to serology and culture in the study of murine Lyme borreliosis. The assay confirmed that, after small numbers of spirochetes are injected intradermally, the heart and bladder, and less frequently the brain, are sites of persistence of the spirochetes. PMID- 8432805 TI - Epidemiological analysis of Candida albicans strains by multilocus enzyme electrophoresis. AB - Genotypic diversity in a collection of 98 isolates of Candida albicans was assessed by multilocus enzyme electrophoresis. Four of the 10 enzyme loci studied were polymorphic. The electrophoretic patterns observed were compatible with those expected for a diploid organism. The 98 isolates were assigned to 14 electrophoretic types, each of which was represented by from 1 to 21 isolates. Samples from various clinical sites of seven bone marrow transplant patients treated in the same unit within a 13-month period were obtained repeatedly. Three patients were found to be colonized with more than one strain. In one patient, flucytosine-resistant strains were isolated after systemic antifungal treatment was started. These isolates had electrophoretic types different from those of the strains that colonized the patient before treatment. There was no evidence that cross-infection between these patients occurred in the hospital. The population structure of C. albicans is discussed in regard to the multilocus genotype data. PMID- 8432806 TI - Detection of Pneumocystis carinii DNA in sputum and bronchoalveolar lavage samples by polymerase chain reaction. AB - A polymerase chain reaction (PCR)-based assay was developed for the detection of Pneumocystis carinii DNA in induced sputum and bronchoscopic alveolar lavage samples. The primer pair was selected from the published sequence of the thymidylate synthase gene of P. carinii derived from infected rats. The amplified DNA fragment of 403 bp was detected by agarose gel electrophoresis and by Southern and slot blot hybridization. No positive reaction was seen with DNA from different microorganisms typically found in the respiratory tract. P. carinii DNA was demonstrated in 30 of 42 sputum samples from immunosuppressed patients, whereas 21 of 42 sputum samples were positive by indirect immunofluorescence (IFL). Among the 42 patients, 14 were receiving prophylactic chemotherapy. In that group, PCR detected P. carinii in nine sputum samples, whereas IFL detected P. carinii in only four sputum samples. A positive PCR result was also seen in 5 of 43 IFL-negative bronchoscopic alveolar lavage samples from patients with respiratory symptoms. The PCR assay detected 10 copies of the target DNA, which corresponds to 10(-18) g of the specific P. carinii sequence. The results indicate that PCR amplification in combination with DNA hybridization is specific and is a more sensitive diagnostic method than IFL for the detection of P. carinii. PMID- 8432807 TI - Typing of Staphylococcus aureus by pulsed-field gel electrophoresis, zymotyping, capsular typing, and phage typing: resolution of clonal relationships. AB - Sixty-nine Staphylococcus aureus isolates from two epidemiologically unrelated sources were typed by pulsed-field gel electrophoresis after SmaI digestion of chromosomal DNA (genome typing), and the results were compared with those obtained by other typing methods: phage typing with the international set of phages, capsular serotyping with monoclonal antibodies against capsular polysaccharides type 5 and 8, and zymotyping by polyacrylamide agarose electrophoresis for esterase polymorphism. A good correlation of S. aureus types was found by these four typing methods. Differentiation increased in the order capsular typing < zymotyping < phage typing < genome typing, yielding 2, 10, 20, and 26 different S. aureus types, respectively. Five of the 26 genome types were further divided into several subtypes revealing clonal relationships. When 36 French S. aureus isolates were compared with 33 German S. aureus isolates, 3 strains representing clonal populations were identical in both groups. S. aureus isolates from patients with cystic fibrosis were also typed at the beginning and the end of a 4-week summer camp for these patients. The results suggested a possible strain transmission during the summer camp. We conclude that genome typing by pulsed-field gel electrophoresis is a powerful tool not only for strain identification but also for the resolution of the clonal relationships of S. aureus strains. PMID- 8432808 TI - Use of ribotyping for characterization of Salmonella serotypes. AB - Forty-five isolates of Salmonella serotype reading, 20 isolates of Salmonella serotype senftenberg, and 56 isolates of Salmonella serotype typhimurium from domestic and wild animals were characterized genotypically to differentiate within serotypes for epidemiologic studies. The genotypic method of characterization used was ribotyping, a method for highlighting highly conserved rRNA genes and associated sequences. Isolates were obtained from diverse geographic sources (farms located in Fresno, Sonoma, Stanislaus, and Yolo counties) as well as different hosts (avian, equine, bovine, murine, and environmental) during a period of 8 months. Within a given serotype, ribotying was able to establish subclassifications (ribotypes) that grouped isolates by a common source regardless of host or geographic origin. There were four distinct ribosomal banding patterns observed for Salmonella serotype reading, six were observed for Salmonella serotype senftenberg, and two were observed for Salmonella serotype typhimurium. PMID- 8432809 TI - Molecular characterization of a novel repetitive element from Pneumocystis carinii from rats. AB - A repetitive DNA sequence, Rp-alpha, was isolated from rat-derived Pneumocystis carinii. The genome of rat-derived P. carinii contained 10 to 15 copies of Rp alpha, which were located on most chromosomes, but no Rp-alpha could be detected in P. carinii derived from either humans or mice. Sequence analysis of two copies of the repeat showed them to be related but distinct. Each of them contained several copies of the 9-base sequence TAACCCTAA, arranged as direct repeats. Oligonucleotides consisting of multimers of this 9mer hybridized to the same set of chromosomes recognized by cloned copies of the Rp-alpha repeat. When used in DNA fingerprinting, the Rp-alpha repeat was capable of distinguishing between different isolates of rat-derived P. carinii. PMID- 8432810 TI - Comparison of DNA fingerprinting and serotyping for identification of avian Pasteurella multocida isolates. AB - The DNA fingerprint profiles and serotypes of 63 avian Pasteurella multocida field isolates, 13 attenuated vaccine isolates (propagated from vaccines manufactured by five companies), and 16 somatic reference strains were compared. DNA fingerprinting established the relationship of isolates that could not be distinguished by serotyping. Of the 76 isolates, 28 DNA fingerprint profiles and 12 somatic types were recognized. One isolate was nonreactive with 16 reference somatic and 5 reference capsule-type antisera. Thirty-one field isolates and seven vaccine isolates were identified as capsule type A. Twenty-nine field isolates and six vaccine isolates were nonencapsulated. Three field isolates were capsule type F. Isolates of capsule types B, D, and E were not found. One field isolate, identified as somatic type 7, had a DNA fingerprint identical to that of the somatic reference type 6 profile. Twelve field isolates had profiles identical to the somatic reference type 3 strain profile; 11 of these were identified as somatic type 3, 4, and 1 was identified as somatic type 3. The DNA fingerprint profiles of 50 field isolates and 13 attenuated vaccine isolates did not match profiles of the 16 somatic type reference strains. Twenty-five DNA fingerprint profiles were recognized from 30 of these field isolates. The DNA fingerprint profiles of 20 field isolates and 13 attenuated vaccine isolates were identical. Three somatic types (3; 3,4; and 4,16) were identified from the field isolates, and two somatic types (3 and 3,4) were identified from the attenuated vaccine isolates. DNA fingerprinting is useful for accurate identification and epidemiologic study of P. multocida isolates. PMID- 8432811 TI - Evaluation of an immunoblot assay for serological confirmation and differentiation of human T-cell lymphotropic virus types I and II. AB - The confirmation of infection with human T-cell lymphotropic virus type I (HTLV I) and type II (HTLV-II) currently involves multiple assays. These include Western blot (immunoblot) (WB) and/or radioimmunoprecipitation assay for detection of antibodies to HTLV-specific viral proteins and polymerase chain reaction and/or peptide-based enzyme immunoassays for differentiating between the two viruses. We undertook an evaluation of a modified WB assay that includes native HTLV-I viral proteins from MT-2 cells spiked with an HTLV-I transmembrane glycoprotein (recombinant p21e) and the HTLV-I- and HTLV-II-specific recombinant proteins MTA-1 and K55. The test panel consisted of well-characterized sera from U.S. blood donors, American Indians, intravenous drug users, and patients seen in sexually transmitted disease clinics. Of 158 HTLV-I/II-seropositive serum specimens tested, 156 (98.7%) were confirmed and typed as HTLV-I or HTLV-II. Of 82 HTLV-I/II-seroindeterminate or -seronegative serum specimens, only 1 was classified as HTLV-II positive: the sample had weak gag p19 and strong gag p24 and env p21e reactivity and was radioimmunoprecipitation assay negative for env gp61/68 but polymerase chain reaction positive for HTLV-II. The specificity of the modified WB for confirming and typing serum samples was therefore 100%. We conclude that this WB assay is useful for confirming and typing HTLV infection and can help simplify HTLV-I/II testing algorithms. PMID- 8432812 TI - An OspA antigen-capture enzyme-linked immunosorbent assay for detecting North American isolates of Borrelia burgdorferi in larval and nymphal Ixodes dammini. AB - An antigen-capture enzyme-linked immunosorbent assay (ELISA) was developed for detecting North American isolates of Borrelia burgdorferi in larval, nymphal, and adult ticks. The assay uses an anti-OspA monoclonal antibody (H5332) for antigen capture and biotin-labelled polyclonal sera with streptavidinhorseradish peroxidase for signal generation. The assay recognized 15 of 15 North American B. burgdorferi isolates and did not cross-react with spirochete antigens of Borrelia hermsii, Borrelia turicatae, Borrelia coriaceae, or Borrelia parkeri, or with tick antigens of Ixodes dammini, Ixodes scapularis, Ixodes pacificus, Ixodes cookei, Ixodes angustus, or Ambylomma americanum. The assay, with a sensitivity of less than 150 spirochetes, can detect infections in larval, nymphal, and adult ticks. In addition to fresh ticks, B. burgdorferi infections in ticks stored frozen, dried, or in 70% ethanol can be determined with the assay. PMID- 8432813 TI - Enzymatic reactions of Clostridium difficile in aerobic and anaerobic environments with the RapID-ANA II identification system. AB - The RapID-ANA II anaerobic identification system (Innovative Diagnostic Systems, Inc., Atlanta, Ga.) was used to determine whether the incubation environment affects enzyme detection. Twenty strains of Clostridium difficile were tested in aerobic, anaerobic, and low-CO2 anaerobic incubation environments. The percentages of enzymes detected in reactions with the following substrates were noted in the three incubation environments: phenylalanine-beta-naphthylamide, aerobic, 0%; anaerobic, 35%; low-CO2 anaerobic, 35%; arginine-beta-naphthylamide, aerobic, 5%; anaerobic, 55%; low-CO2 anaerobic, 75%; pyrrolidonyl-beta naphthylamide, aerobic, 5%; anaerobic, 65%; low-CO2 anaerobic, 65%. When the aerobic incubation environment was compared with either the anaerobic or the low CO2 anaerobic incubation environments, the results were statistically different with respect to enzyme detection in reactions with the substrates listed above. The results for the anaerobic and low-CO2 anaerobic environments were not statistically different. The study was repeated twice. Statistical comparisons between the three environments were consistent with the results presented above, with the following exceptions. The aerobic and the anaerobic environments were not different in a reaction with phenylalanine-beta-naphthylamide in one of the runs, and there was no significant difference between the three environments in a reaction with arginine-beta-naphthylamide in another run. These results suggest that some of the enzymes used in the identification of clinical anaerobes appear to be inactive in an environment containing oxygen. PMID- 8432814 TI - Improved isolation of Chlamydia trachomatis from a low-prevalence population by using polyethylene glycol. AB - The effect of polyethylene glycol (PEG) on the isolation of Chlamydia trachomatis was evaluated in our laboratory. Initial range-finding experiments demonstrated that the number of chlamydial inclusion bodies increased with increasing PEG concentrations. However, PEG concentrations above 10.5% became progressively more toxic to the McCoy cell monolayers. When 50 frozen clinical Chlamydia isolates were inoculated onto McCoy cell cultures with and without 7% PEG, the PEG-treated cultures produced three- to fivefold more chlamydial inclusions than cultures without PEG. This enhancement was also observed when 1,144 fresh clinical specimens from a low-prevalence population were tested. With fresh clinical specimens, PEG-treated cultures produced two- to sixfold more inclusions than standard cultures. The addition of 7% PEG to the chlamydial overlay medium significantly increased the number of inclusions in each culture, improved the sensitivity of the culture, and decreased the probability of missing a weakly positive specimen. PMID- 8432816 TI - Comparison of four decontamination methods for recovery of Mycobacterium avium complex from stools. AB - The presence of Mycobacterium avium complex (MAC) in stool specimens may be a predictor of disseminated MAC infection, yet the methods for decontaminating stools have not been evaluated for their usefulness in recovering MAC organisms. In the present study, four decontamination methods commonly used to recover acid fast bacteria from respiratory specimens were compared for their utility in recovering MAC from stool specimens. Ten strains of MAC were used at a level of 10(4) to 10(6) CFU to seed the stool specimens. Specimens were divided into four portions and were decontaminated by using the following treatments: (i) N-acetyl L-cysteine-sodium hydroxide (NALC-NaOH), (ii) cetylpyridinium chloride-sodium chloride (CPC-NaCl), (iii) oxalic acid, or (iv) benzalkonium chloride-trisodium phosphate (BC-TSP). The specimens were then plated onto a total of five pieces of selective and nonselective egg- and agar-based media. The oxalic acid method yielded the greatest number of MAC CFU from seeded stool samples; this was followed by NALC-NaOH, BC-TSP, and CPC-NaCl. The difference between the oxalic acid method and each of the other methods was statistically significant (analysis of variance at the 95% significance level). Although more MAC CFU was recovered from seeded stool samples by using oxalic acid than NALC-NaOH, no difference in culture positivity rates was observed when the two methods were used to test 368 clinical stool specimens processed with either oxalic acid (164 specimens) or NALC-NaOH (204 specimens) (P = 0.07) or 67 specimens processed by both methods (P = 0.77). The oxalic acid and NALC-NaOH decontamination methods both appear to be useful for the recovery of MAC organisms from stool specimens. PMID- 8432815 TI - Identification of a clone of Escherichia coli O103:H2 as a potential agent of hemolytic-uremic syndrome in France. AB - In a French multicenter study, six verocytotoxin-producing Escherichia coli strains were isolated from the stools of 6 of 69 children suffering from hemolytic-uremic syndrome. All strains belonged to serotype O103:H2, a serotype commonly associated with diarrhea in weaned rabbits in France. To determine whether the strains from humans and rabbits were genetically related, they were compared by analyzing their esterase electropherotypes and the restriction fragment length polymorphisms of the ribosomal DNA regions. A common clonal origin of these pathogenic strains was suggested by their identical esterase electropherotypes and their identical ribotypes, in addition to their identical serotypes. However, strains from humans, which are cytotoxic for HeLa cells through the production of verocytotoxin type 1, do not show adhesion in vitro to HeLa 229 cells and cannot infect rabbits. On the other hand, strains from rabbits do not carry the verocytotoxin type 1 gene, are not cytotoxic for Hela cells, and adhere to ileal villi and HeLa 229 cells because of the expression of their 32 kDa adhesin. Our results therefore identify a clone of verocytotoxin-producing E. coli O103:H2 as a potential agent of hemolytic uremic syndrome in France. They further suggest that clones from humans and rabbits probably have a common origin but that adaptation to the two species occurred by different mechanisms. Thus, they eliminate the hypothesis that the species is horizontally transmitted between rabbits and humans. PMID- 8432817 TI - Mammalian epithelial cell line kit for detection of Clostridium difficile toxin. AB - The performance characteristics of a mammalian epithelial (MEP) cell line kit (Cytotoxi Test; Advanced Clinical Diagnostics, Toledo, Ohio) for the detection of Clostridium difficile toxin was compared with that of conventional tissue culture assays with human embryonic lung (HEL) cells in shell vials and human foreskin fibroblasts (HFFs) in test tubes. One hundred forty-nine stool samples were tested. The MEP cells were at least as sensitive as the HEL cells for use in C. difficile toxin detection. Results for the MEP cells were also obtained considerably more rapidly than those for HEL cells when the cells were examined at 4 and 24 h and then every 24 h for up to 5 days. Approximately one-third of all positive MEP cells were detected at 4 h and 95% were detected by 48 h. In comparison, in the HEL shell vial monolayers, only 6% of the positive cells were detectable at 4 h and 76% were detectable at 48 h. The times for C. difficile toxin-induced cytotoxicity in HFF cells were similar to those in HEL cells. Shell vials carrying HEL cell monolayers (ViroMed Laboratories Inc., Minnetonka, Minn.) are a sensitive and reliable commercial source for the detection of C. difficile toxin, although they cannot detect C. difficile as rapidly as the Cytotoxi test with the MEP cell monolayers. PMID- 8432818 TI - Serologic analysis of white-tailed deer sera for antibodies to Borrelia burgdorferi by enzyme-linked immunosorbent assay and western immunoblotting. AB - White-tailed deer serum samples were collected in the Minneapolis-St. Paul, Minn., metropolitan area during the fall and winter months from 1989 to 1992 and analyzed for antibodies to Borrelia burgdorferi, the etiologic agent of Lyme borreliosis. Ninety-eight percent of the serum samples were collected from regions where currently the vector tick, Ixodes dammini, is nonexistent. Antibodies to B. burgdorferi were detected in 2.2% of 508 samples by enzyme linked immunosorbent assay, and their presence was confirmed by Western immunoblot analysis. Western immunoblotting yielded mean numbers of reactive bands of 0.1 and 6.0 for samples that were negative and positive for antibodies by enzyme-linked immunosorbent assay, respectively. The molecular weights of the antigens in many of the reactive bands from positive samples were similar to the molecular weights of antigens reactive with samples from humans with Lyme borreliosis. An antibody response to the major outer surface proteins A and B was not detected. Serologic analysis of deer sera may provide a valuable method for surveillance programs designed to monitor the spread of B. burgdorferi in nature. PMID- 8432819 TI - Detection of parvovirus B19 in donated blood: a model system for screening by polymerase chain reaction. AB - A highly sensitive and rapid method for routinely screening large numbers of donated blood units for parvovirus B19 by the polymerase chain reaction (PCR) was developed. Over a 3-month trial period in Edinburgh, B19 DNA was detected in 6 of 20,000 consecutive units of blood (0.03%), in concentrations ranging from 2.4 x 10(4) to 5 x 10(10) copies of viral DNA per ml. Seroconversion for B19-specific immunoglobulin M and immunoglobulin G and disappearance of circulating B19 DNA occurred in the interval between donation and recall in four of the five implicated donors who could be recalled. B19 DNA was detected in 18 of 27 separate batches of non-heat-treated factor VIII and IX concentrate manufactured from donated plasma unscreened for B19 DNA. Dry-heat treatment at 80 degrees C for 72 h reduced but did not always eliminate detectable B19 from factor VIII concentrates, consistent with recent observations that current methods for virus inactivation during blood product manufacture are insufficient to entirely eliminate B19 infectivity. The methods developed in this study for PCR screening could be applied routinely to prevent transfusion of B19 in blood and blood products and could play an important role in the prevention of iatrogenic transmission of infection. PCR screening could also be used for detection and exclusion of a range of other transmission-associated viruses for which current serological detection methods are only partially effective. PMID- 8432820 TI - Purification of the 115-kilodalton exoantigen of Cryptococcus neoformans and its recognition by immune sera. AB - A 115-kDa exoantigen produced by Cryptococcus neoformans recognized by the previously described murine monoclonal antibody 7C9 has been purified from culture filtrate by a combination of membrane ultrafiltration, isoelectric focusing, and preparative gel electrophoresis. It is produced in late-log-phase cultures and is present in greater amounts in cultures grown at 25 degrees C than in those grown at 37 degrees C. Recognition of the antigen by 7C9 on immunoblots is abolished by the proteolytic enzymes papain and trypsin. The antigen is a glycoprotein bearing N-linked oligosaccharides, of which mannose is an important constituent. It does not appear to have proteolytic activity and is acidic, with a pI of 3 to 3.2. Its relationship to previously described C. neoformans mannoprotein is unclear since 7C9 shows only very weak cross-reactivity with a purified sample of the latter. Sera from patients infected with C. neoformans exhibited strong recognition of the glycoprotein as shown by immunoenzyme development of Western immunoblots, indicating its possible significance as a marker of disease. PMID- 8432821 TI - An OspA serotyping system for Borrelia burgdorferi based on reactivity with monoclonal antibodies and OspA sequence analysis. AB - A total of 136 Borrelia burgdorferi sensu latu strains from various biological sources (ticks, human skin, and cerebrospinal fluid) and geographical sources (Europe and North America) were investigated by Western blot (immunoblot) with eight monoclonal antibodies against different epitopes of the outer surface protein A (OspA). On the basis of the differential reactivities of these monoclonal antibodies, seven OspA serotypes were defined. As determined by 16S rRNA sequence analysis, these serotypes correlated well with recently delineated genospecies: serotype 1 corresponds to B. burgdorferi sensu strictu, serotype 2 corresponds to group VS461, and serotypes 3 to 7 correspond to Borrelia garinii sp. nov. (G. Baranton, D. Postic, I. Saint Girons, P. Boerlin, J.-C. Piffaretti, M. Assous, and P. A. D. Grimont, Int. J. Syst. Bacteriol. 42:378-383, 1992). Antigenic differences were confirmed by partial sequence analysis of OspA of representatives of each serotype. Comparative sequence analysis suggested that serotype 5 OspA resulted from genetic recombination of serotype 4 and 6 ospA genes. Serotype 2 (group VS461) was most prevalent among European skin isolates (49 of 62 isolates). Among all B. garinii strains included in this study, serotype 6 was most frequently found in ticks and only rarely in human skin and cerebrospinal fluid, whereas serotypes 4 and 5 were isolated from patients but never from ticks. Our data suggest different pathogenic potentials and organotropisms of distinct OspA serotypes and raise the question of true antigenic variation among B. garinii strains. PMID- 8432822 TI - Colonization by enteroaggregative Escherichia coli in travelers with and without diarrhea. AB - Enteroaggregative Escherichia coli (EAggEC) has been found to be associated with pediatric diarrhea in developing countries. In order to determine the role of EAggEC as an agent of traveler's diarrhea, we used a sensitive and specific DNA probe for EAggEC to screen bacterial colony blots from 278 volunteers before and after travel. Colonization with EAggEC was infrequent (2.5%) prior to travel but rose to 27 to 33% after travel in volunteers who took either placebo or trimethoprim-sulfamethoxazole. Travelers who took trimethoprimsulfamethoxazole were colonized with organisms that were uniformly resistant to that antimicrobial agent; when volunteers received ciprofloxacin, colonization with EAggEC was prevented (2.0%). Although colonization rates were high in the placebo and trimethoprim-sulfamethoxazole groups, only a minority of travelers who were colonized with EAggEC experienced diarrhea. On the basis of our data, we suggest that colonization with EAggEC alone is not sufficient to cause traveler's diarrhea. PMID- 8432823 TI - Serotyping of Cryptococcus neoformans by using a monoclonal antibody specific for capsular polysaccharide. AB - The importance of epidemiological studies of cryptococcosis has increased since the beginning of the AIDS epidemic. Cryptococcus neoformans exists in two varieties defining four serotypes, Cryptococcus neoformans var. neoformans (serotypes A and D) and Cryptococcus neoformans var. gattii (serotypes B and C). The varieties are easy to distinguish by their differences of growth on diagnostic media. We propose here an easy serotyping method combining diagnostic media and a direct immunofluorescence assay with one monoclonal antibody (E1) specific for cryptococcal polysaccharide. The method was validated by the blinded testing of four to five reference strains of each serotype. Immunofluorescence patterns were characteristic of a given serotype provided that the variety of the strain had been defined before. For C. neoformans var. neoformans, a bright, homogeneous staining with several cell aggregates was characteristics of serotype A, whereas only a few serotype D cells were positive. For C. neoformans var. gattii, a completely negative isolate was serotype C, whereas the population of serotype B included a majority of negative cells but also included positive cells with a speckled pattern. The method was then used to serotype 156 clinical isolates from France and isolates from areas where C. neoformans var. gattii was endemic before the AIDS epidemic (13 strains from Rwanda and Zaire and 5 strains from Australia). The specificity of E1 was defined by its reactivity with various Cryptococcus spp. and analyzed according to the described cryptococcal antigenic factors. We conclude from this study that E1 provides a rapid and reliable means to serotype multiple isolates of C. neoformans. PMID- 8432824 TI - Comparison of isolation methods for the recovery of Bordetella bronchiseptica and Pasteurella multocida from the nasal cavities of piglets. AB - Nasal swabs from 241 piglets from 12 herds with clinical atrophic rhinitis and 283 piglets from 14 herds without clinical atrophic rhinitis were examined for the presence of Bordetella bronchiseptica and/or Pasteurella multocida. For B. bronchiseptica, swabs were streaked on three selective media. Blood agar supplemented with cephalexin was the most satisfactory selective culture medium for the isolation of B. bronchiseptica. For P. multocida, swabs were also streaked on three selective media. Mice were also used for isolation of P. multocida from the nasal cavities of pigs. The mouse inoculation test was not found to be the definitive test for the isolation of P. multocida. A significant number of P. multocida strains were avirulent in the mouse model. The modified Knight medium (without potassium tellurite) was the best single method for isolating P. multocida. However, a combination of mouse passage and direct culture on selective media increased the rate of isolation. There was no marked difference in the prevalence of B. bronchiseptica or P. multocida in swine herds with or without clinical atrophic rhinitis. Both capsular types A and D were present in the nasal cavities of the pigs with or without clinical atrophic rhinitis. PMID- 8432825 TI - Improved primary immunodiagnosis of alveolar echinococcosis in humans by an enzyme-linked immunosorbent assay using the Em2plus antigen. AB - Alveolar echinococcosis (AE) in humans is generally a fatal disease when not diagnosed early enough to provide curative treatment such as radical surgery. Immunodiagnosis for early detection of AE was improved by the isolation of an affinity-purified metacestode Em2 antigen and by the synthesis of recombinant Echinococcus multilocularis antigen II/3-10. Both antigens were individually assessed by enzyme-linked immunosorbent assay (ELISA) and demonstrated high specificities and diagnostic sensitivities, although both missed approximately 4 to 11% of diagnostic cases of AE. To provide an optimal serodiagnostic test, we investigated the two purified antigens by using a test employing a mixture of both purified antigens (designated Em2plus antigen) in one assay. For comparative purposes, crude E. multilocularis and Echinococcus granulosus metacestode antigens were investigated as well. The Em2plus ELISA proved to be the optimal diagnostic test with the highest diagnostic sensitivity, 97%, in serum samples from 140 patients with AE and an overall specificity of 99% for infections due to other Echinococcus and non-Echinococcus parasites. The new test combination (Em2plus ELISA) is suggested for the serodiagnosis of AE in patients and for seroepidemiological surveys. PMID- 8432826 TI - Cultivation of Mycobacterium paratuberculosis from bovine fecal samples by using elements of the Roche MB Check system. AB - Components of a commercially available, nonradiometric, biphasic (liquid medium then solid medium) system for the detection of Mycobacterial species, Roche MB Check, were adapted for the isolation of Mycobacterium paratuberculosis from bovine fecal specimens. A two-stage culture procedure was developed in which processed fecal samples were incubated in modified commercial liquid medium and then subcultured onto Herrold's egg yolk medium with mycobactin. By using known culture-positive samples and/or samples from animals clinically affected with paratuberculosis, it was found that visible colonial growth on solid media could be obtained after 4 weeks of incubation in liquid medium containing egg yolk and mycobactin followed by 8 weeks of incubation on Herrold's egg yolk medium. In the second part of the study, conventional fecal culture (sample sedimentation in hexadecylcetylpyridinium chloride followed by incubation on Herrold's egg yolk medium) was compared with the two-stage system using a two-step centrifugation technique for sample preparation. One hundred fecal samples from clinically normal but absorbed-enzyme immunoassay-positive cattle were used for the comparison. Conventional culture yielded a sensitivity of 16.5%, whereas the sensitivity of the two-stage system was 29.4%. When used in parallel, the tests detected 36.5% of the samples. There was no significant difference between the two methods in the time taken to obtain visible colonies. These results indicate that the two-stage method is a sensitive method for isolation of M. paratuberculosis from fecal samples obtained from cattle with clinical paratuberculosis. In addition, the two-stage system is more sensitive than conventional culture for the isolation of M. paratuberculosis from subclinically infected cattle. PMID- 8432827 TI - Comparison of Rambach agar, SM-ID medium, and Hektoen Enteric agar for primary isolation of non-typhi salmonellae from stool samples. AB - Stool samples (n = 504) were streaked simultaneously onto Rambach agar (R agar; E. Merck, Darmstadt, Germany), SM-ID medium (bioMerieux S.A., Montalieu-Vercieu, France), and Hektoen Enteric (HE) agar (BBL Becton-Dickinson, Baltimore, Md.) in order to evaluate the performances of the first two media in comparison with that of the well-established HE agar. Following overnight cultivation at 37 degrees C, 29 samples (5.8%) were positive for non-typhi salmonellae on at least one of the three media. Sensitivities and specificities were 69 and 98%, 79 and 85%, and 100 and 79% for R, SM-ID, and HE agars, respectively. On the basis of the poor sensitivities, R and SM-ID agars are not recommended as primary plating media when screening for non-typhi salmonellae. However, the high specificity of R agar may help to reduce the work load when this medium is used for plating after enrichment. PMID- 8432828 TI - Typing of Clostridium difficile by western immunoblotting with 10 different antisera. AB - Western blotting (immunoblotting) with antisera against each of 10 reference serogroups was evaluated as a means of typing Clostridium difficile. A total of 164 clinical isolates of C. difficile were tested. Variations in band profiles in each serogroup were used to type isolates into subserogroups. This technique was useful for an epidemiological investigation. PMID- 8432829 TI - Evaluation of Gen-Probe's Histoplasma capsulatum and Cryptococcus neoformans AccuProbes. AB - Gen-Probe's DNA probes were evaluated for use in the identification of clinical isolates of Histoplasma capsulatum var. capsulatum and Cryptococcus neoformans. Ninety-five mould-phase fungi were probed, including 41 isolates of H. capsulatum var. capsulatum. Similarly, 98 yeasts, including 42 C. neoformans isolates, were examined by using the C. neoformans DNA probe. In the study, both probes demonstrated 100% specificity and 100% sensitivity. Their use in the clinical laboratory may significantly reduce the time required for definitive identification of fungi. PMID- 8432830 TI - Cervical adenitis caused by Staphylococcus epidermidis. AB - Staphylococcus epidermidis, a human commensal, is a common cause of bacteremia in immunocompromised patients with indwelling medical devices. We report a case of isolated cervical adenitis caused by S. epidermidis in an immunocompetent patient and comment on the presumed pathogenesis. PMID- 8432831 TI - Effect of gamma irradiation on reactivity of rinderpest virus antigen with bovine immune serum in enzyme-linked immunosorbent assays and virus neutralization and indirect fluorescent-antibody tests. AB - Gamma irradiation effectively inactivated gradient-purified rinderpest virus. Irradiated antigen and sera remained functional in enzyme-linked immunosorbent assays, virus neutralization tests, and indirect fluorescent-antibody tests. Irradiation, however, led to a dose-dependent decrease in reactivity, particularly significant (P < 0.05) when both reagents were irradiated. To avoid false-positive reactions, only one reagent (serum or antigen) may be irradiated. PMID- 8432832 TI - Evaluation of the Vitek EPS enteric pathogen screen card for detecting Salmonella, Shigella, and Yersinia spp. AB - We evaluated the Vitek EPS card as a screen for the enteric pathogens Salmonella spp., Shigella spp., and Yersinia enterocolitica. Salmonella spp., Shigella spp., and Y. enterocolitica (125, 54, and 5 isolates, respectively) and 81 nonenteric pathogens that might be selected for screening from primary plates (non-lactose fermenters) were tested. The EPS card correctly identified 183 of 184 pathogens tested (sensitivity, 99.5%). Of 81 nonenteric pathogens screened with the EPS card, 8 were identified as possible enteric pathogens (specificity, 90.1%). We reviewed our stool culture records over the past 1.5 years and analyzed the specificities of TSI-urea screens for 300 stool cultures that had suspicious colonies. From 55 of 300 stool cultures, either Salmonella spp. or Shigella spp. were isolated, and from 245 stool cultures, no pathogen was isolated. Of the 245 negative cultures, 166 gave false-positive screening-test results that resulted in further biochemical identification procedures (Analytab Products or Vitek identification). Thus, the specificity of the TSI-urea screen in our experience was 32.2%. The Vitek EPS card was shown to be a more cost-effective screening procedure than the TSI-urea screen. PMID- 8432833 TI - Incidental finding of a microsporidian parasite from an AIDS patient. AB - Light microscopic examination of feces from a human immunodeficiency virus positive patient with chronic diarrhea, anorexia, and lethargy revealed the presence of numerous refractile bodies resembling microsporidian spores. They were subsequently identified as belonging to the genus Nosema on the basis of their ultrastructural characteristics. However, the microsporidia were enclosed within striated muscle cells, suggesting that they were probably ingested in food; thus, this represented an incidental finding rather than a true infection. PMID- 8432834 TI - Protein and antigenic analysis of Borrelia burgdorferi isolated in northern Italy: computerized analysis of phenotypic characteristics. AB - Four Borrelia burgdorferi strains isolated in the same restricted geographic area share different protein patterns on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The use of polyclonal rabbit antisera and a battery of monoclonal antibodies directed toward the immunodominant proteins OspA, OspB, and pC also revealed different epitope distributions and specificities of these antigens on the strains examined. For the first time, a computerized analysis of these phenotypic characters was done mainly by cluster analysis. The computerized analysis revealed the levels of similarities among the strains and indicated, on a quantitative basis, that one of them is much closer to the American strain B31 than to the other strains. PMID- 8432835 TI - Fatal pneumonia due to Serratia proteamaculans subsp. quinovora. AB - Serratia proteamaculans subsp. quinovora was isolated from several samples (blood cultures, tracheal aspirates, pleural effusion) from a patient with pneumonia. This is the first clinical isolate and the first documented human infection caused by this organism. PMID- 8432836 TI - Genus-specific polymerase chain reaction for the mycobacterial dnaJ gene and species-specific oligonucleotide probes. AB - Identification of tuberculous and nontuberculous mycobacteria by biochemical methods is a long-term process that takes up to 8 weeks for completion and requires expertise to interpret the results. In order to detect and differentiate the major pathogenic mycobacterial species, we developed genus-specific primers that amplify the dnaJ gene from the broad spectrum of mycobacterial species and determined the nucleotide sequences within the dnaJ genes from 19 mycobacterial species (Mycobacterium tuberculosis, M. bovis, M. bovis BCG, M. africanum, M. microti, M. kansasii, M. marinum, M. gastri, M. simiae, M. scrofulaceum, M. szulgai, M. gordonae, M. avium, M. intracellulare, M. xenopi, M. fortuitum, M. chelonei, M. haemophilum, and M. paratuberculosis). On the basis of the dnaJ gene sequences, we developed dot blot hybridization analysis with species-specific oligonucleotide probes for the M. tuberculosis complex. M. avium, M. intracellulare, and M. kansaii, allowing a rapid identification of these species following polymerase chain reaction for the dnaJ gene. We conclude that polymerase chain reaction with the genus-specific primer that amplifies the dnaJ genes and subsequent dot blot analysis with species-specific oligonucleotide probes are most useful for differential diagnosis of tuberculosis and nontuberculous mycobacterial infections. PMID- 8432837 TI - Evaluation of the PACE 2 Neisseria gonorrhoeae assay by three public health laboratories. AB - The Gen-Probe PACE 2 DNA probe assay for Neisseria gonorrhoeae was compared with conventional culture techniques in three Florida public health laboratories with 436 patients (271 females and 165 males). The prevalence rates based on culture were 19.9, 55.8, and 33.5% for females, for males, and overall, respectively. Twenty-seven probe-positive specimens gave negative culture results. Twenty of these specimens were resolved as true positives after retesting with a probe competition assay. The resolved sensitivity, specificity, positive predictive value, and negative predictive value were 99.4, 99.6, 99.4, and 99.6%, respectively. PMID- 8432838 TI - Immune response against lipopolysaccharide and invasion plasmid-coded antigens of shigellae in Vietnamese and Swedish dysenteric patients. AB - The peripheral immune responses of adult Vietnamese patients infected with Shigella dysenteriae 1 and Shigella flexneri 1b and 2a and those of S. flexneri infected Swedish patients were studied against various lipopolysaccharide and invasion plasmid-coded antigens (Ipa-s) and compared with the titers for the corresponding local healthy populations. Both Vietnamese and Swedish patients reacted with significant (P, < 0.05) titer increases in the immunoglobulin A and G classes against the homologous lipopolysaccharide antigen. However, significant titer responses against the Ipa-s were seen among only the Swedish patients. We surmise that the weak-to-moderate responses against the Ipa-s in Vietnamese patients are due to the fact that the high level of titers induced by previous infections in the local population could not be considerably increased further by a recent infection. PMID- 8432839 TI - Mixed-morphotype broth microdilution susceptibility testing of Pseudomonas aeruginosa from cystic fibrosis patients. AB - Multiple morphotypes of Pseudomonas aeruginosa isolated from 50 respiratory specimens of cystic fibrosis patients were tested for correlation of broth microdilution susceptibility results of a mixed-morphotype inoculum with a predicted antibiogram of the individual isolates. The overall correlation was 96.0%, with only 1.6% very major or major errors. PMID- 8432840 TI - Fast DNA isolation from Histoplasma capsulatum: methodology for arbitrary primer polymerase chain reaction-based epidemiological and clinical studies. AB - The arbitrary primer polymerase chain reaction (also called random amplified polymorphic DNA, or RAPD) is a DNA fingerprinting method that provides an efficient, sensitive way of discriminating between independent isolates of Histoplasma capsulatum, but its widespread application has been hampered by the arduous 2-day procedure traditionally used to extract DNA from H. capsulatum. We present here a quick (approximately 2-h) extraction method and show that the resultant DNA is suitable for sensitive and reproducible identification of individual strains of this pathogenic fungus. PMID- 8432841 TI - Type 5 and 8 capsular polysaccharides are expressed by Staphylococcus aureus isolates from rabbits, poultry, pigs, and horses. AB - A total of 103 Staphylococcus aureus isolates from rabbits (n = 37), poultry (n = 33), pigs (n = 27), and horses (n = 6) and 14 Staphylococcus intermedius isolates from wild animals were serotyped for capsular polysaccharide types 5 and 8 by an enzyme-linked immunosorbent assay using polyclonal rabbit antibodies. About 98% of the S. aureus isolates were typeable. Type 5 was predominant in the poultry (75.8%) and pig (66.7%) isolates, whereas type 8 was more frequent among the isolates from rabbits (59.5%) and horses (83.3%). By contrast, none of the 14 S. intermedius isolates was typeable. PMID- 8432842 TI - Origin of HEp-2 cells used for culture of chlamydiae. PMID- 8432843 TI - Nucleic acid sequence citations: need for more-specific guidelines. PMID- 8432844 TI - Anoxia? Don't get excited! PMID- 8432845 TI - Intravenous IgG: supertherapy for superantigens? PMID- 8432846 TI - Prolongation of survival of rat cardiac allografts by T cell vaccination. AB - Administration of attenuated, activated autoimmune T lymphocytes to syngeneic mice and rats has been shown to prevent or induce remission of experimental autoimmune diseases specific for the autoimmune T cells. The process has been termed "T cell vaccination." In a recent study, T cell vaccination was done using T cells sensitized to rat alloantigens. The procedure produced a significant reduction of the mixed lymphocyte reaction (MLR) against allogeneic cells. The reduction in MLR was not specific: Vaccination with T cells specific for stimulator cells of one allotype led to a reduced MLR stimulated by cells of another allotype. The present study was undertaken to examine whether T cell vaccination can induce tolerance to transplantation antigens in vivo. We used the model of heterotopic cardiac transplantation in rats. We now report that vaccinating rats with syngeneic, activated, alloantigen-primed T lymphocytes significantly prolonged survival of rat cardiac allografts. The effect of T cell vaccination was most evident when the T cells had been obtained from rats specifically sensitized against the donor rats: Brown-Norway (BN) allografts in control Wistar rats survived 8.5 +/- 0.4 d while BN allografts survived 29.2 +/- 7.1 d in Wistar rats that had been vaccinated with Wistar anti-BN cells. Vaccination of Wistar rats with Wistar anti-hooded T cells prolonged survival of BN heart allografts to a lesser but significant degree (13.0 +/- 1.1 d). Thus, T cell vaccination of recipients can prolong survival of allografts. PMID- 8432847 TI - Elevated plasma concentrations of lipoprotein(a) in patients with end-stage renal disease are not related to the size polymorphism of apolipoprotein(a). AB - Patients with terminal renal insufficiency suffer from an increased incidence of atherosclerotic diseases. Elevated plasma concentrations of lipoprotein(a) [Lp(a)] have been established as a genetically controlled risk factor for these diseases. Variable alleles at the apo(a) gene locus determine to a large extent the Lp(a) concentration in the general population. In addition, other genetic and nongenetic factors also contribute to the plasma concentrations of Lp(a). We therefore investigated Apo(a) phenotypes and Lp(a) plasma concentrations in a large group of patients with end-stage renal disease (ESRD) and in a control group. Lp(a) concentrations were significantly elevated in ESRD patients (20.1 +/ 20.3 mg/dl) as compared with the controls (12.1 +/- 15.5 mg/dl, P < 0.001). However, no difference was found in apo(a) isoform frequency between the ESRD group and the controls. Interestingly, only patients with large size apo(a) isoforms exhibited two- to fourfold elevated levels of Lp(a), whereas the small size isoforms had similar concentrations in ESRD patients and controls. Beside elevated Lp(a) concentrations, ESRD patients had lower levels of plasma cholesterol and apolipoprotein B. These results show that elevated Lp(a) plasma levels might significantly contribute to the risk for atherosclerotic diseases in ESRD. They further indicate that nongenetic factors related to renal insufficiency or other genes beside the apo(a) structural gene locus must be responsible for the high Lp(a) levels. PMID- 8432848 TI - Independently derived murine glomerular immune deposit-forming anti-DNA antibodies are encoded by near-identical VH gene sequences. AB - To examine the influence of variable region sequences on the capacity of individual lupus autoantibodies (autoAb) to form glomerular immune deposits, the complete VH and VL region sequences of three anti-DNA mAb that produced morphologically similar immune deposits after administration to normal mice were determined. The Ig were independently derived from 1-mo-old (H238, IgM), 3-mo-old (H8, IgG2a), and 6-mo-old (H161, IgG3) MRL-lpr/lpr mice, and they all produced subendothelial and mesangial immune deposits after passive transfer to normal mice. In addition, H238 and H161 produced granular deposits in small extraglomerular vessels. The mAb had nearly identical VH gene sequences; H8 differed from H238 and H161 by a single nucleotide in FR1 that resulted in a histidine for glutamine substitution. This VH gene sequence was also > 99% homologous to another anti-DNA Ab (termed H241), that we previously reported to produce glomerular immune deposits in a similar morphologic pattern. H161 and H238 were encoded by DFL16 and JH2 genes, whereas H8 was encoded by a JH4 gene. Different Vk family genes were used to encode the three mAb, however H161 and H238 both used a Jk5 gene. The results indicate that an identical or highly related VH gene is used to encode a subgroup of murine lupus autoAb that share immune deposit forming properties. Furthermore, they raise the possibility that amino acid residues independent from those encoded by VH genes may be influential in immune deposit formation at extraglomerular sites. PMID- 8432849 TI - Inhibition of human erythroid colony-forming units by tumor necrosis factor requires beta interferon. AB - We have previously reported that inhibition of human CFU-erythroid (E) colony formation by tumor necrosis factor (TNF) is an indirect effect mediated by a soluble factor released from a fraction of marrow accessory cells which are predominantly stromal elements (Means, R. T., Jr., E. N. Dessypris, and S. B. Krantz. 1990. J. Clin. Invest. 86:538-541). Further studies reported here identify a mediator of this effect. The inhibitory effect of recombinant TNF on marrow CFU-E is ablated by neutralizing antibodies to human beta IFN, but not by antibodies to gamma IFN or IL-1. Anti-beta IFN also neutralizes the inhibitory effect of conditioned medium prepared from marrow cells exposed to TNF. Human beta IFN inhibits colony formation by unpurified marrow CFU-E as well as highly purified CFU-E generated from peripheral blood progenitors, and limiting dilution analysis shows that this is a direct inhibitory effect. TNF has been implicated in the pathogenesis of the anemia of chronic diseases since blood TNF levels are elevated in many patients with this syndrome, and since exposure to TNF produces a similar anemia in either humans or mice. The present study demonstrates that beta IFN is a required mediator of this inhibitory effect on erythropoiesis. PMID- 8432850 TI - 31P-magnetic resonance spectroscopy assessment of subnormal oxidative metabolism in skeletal muscle of renal failure patients. AB - In hemodialysis patients, erythropoietin increases hemoglobin, but often the corresponding increase in peak oxygen uptake is low. The disproportionality may be caused by impaired energy metabolism. 31P-magnetic resonance spectroscopy was used to study muscle energy metabolism in 11 hemodialysis patients, 11 renal transplant recipients, and 9 controls. Measurements were obtained during rest, static hand-grip, and rhythmic hand-grip; recoveries were followed to baseline. During static hand-grip, there were no between-group differences in phosphocreatine (PCr), inorganic phosphate (Pi), or PCr/(PCr + Pi), although intracellular pH was higher in hemodialysis patients than transplant recipients. During rhythmic hand-grip, hemodialysis patients exhibited greater fatigue than transplant recipients or controls, and more reduction in PCr/(PCr + Pi) than transplant recipients. Intracellular pH was higher in controls than either hemodialysis patients or transplant recipients. Recoveries from both exercises were similar in all groups, indicating that subnormal oxidative metabolism was not caused by inability to make ATP. The rhythmic data suggest transplantation normalizes PCr/(PCr + Pi), but not pH. In hemodialysis patients, subnormal oxidative metabolism is apparently caused by limited exchange of metabolites between blood and muscle, rather than intrinsic oxidative defects in skeletal muscle. PMID- 8432851 TI - Androgen regulation of epidermal growth factor receptor binding activity during fetal rabbit lung development. AB - Fetal lung development progresses in a sex-specific manner with male fetuses exhibiting delayed maturation. Androgens, both exogenous and endogenous, inhibit while epidermal growth factor (EGF) enhances fetal lung development. We hypothesized that one mechanism responsible for the delay in male fetal lung development is an androgen-induced delay in EGF receptor binding activity. We measured EGF binding in sex-specific fetal rabbit lung plasma membranes isolated from control fetuses (days 21, 23, 25, 27, 29, and 30 of gestation) and from androgen-treated fetuses (days 21, 23, and 27 of gestation) that had been continuously exposed in vivo to exogenous 5 alpha-dihydrotestosterone from day 12 through 27 of gestation. Specific binding of EGF was significantly lower in male than in female fetal lung tissue isolated from controls at day 21 of gestation. Scatchard analysis revealed that this decrease in EGF binding was associated with decreased EGF receptor density without any significant change in affinity. Prenatal exogenous androgen treatment led to decreased EGF binding in fetal rabbit lung tissue from both sexes secondary to a decrease in EGF receptor density. These findings suggest that one mechanism responsible for the delay in male fetal lung maturation is an androgen-induced delay in EGF receptor binding activity during fetal lung development. PMID- 8432852 TI - Interference of glycogenolysis with glycolysis in pancreatic islets from glucose infused rats. AB - When pancreatic islets isolated from rats infused for 48-72 h with a hypertonic solution of D-glucose were incubated for two successive periods of 10 min each, in the presence first of 16.7 mM and then 2.8 mM D-[U-14C]glucose, the total output of L-lactic acid during the second incubation was as high as that recorded during the first incubation, while the specific radioactivity of L-lactic acid dramatically decreased during the second incubation. In islets from normoglycemic rats, however, the total output of L-lactic acid decreased and its specific radioactivity modestly increased as the concentration of D-glucose was lowered from 16.7 to 2.8 mM. Such contrasting results indicate that in the glycogen-rich islets isolated from glucose-infused rats, the fall in extracellular D-glucose concentration was not accompanied by a parallel fall in glycolytic flux, the decreased utilization of exogenous D-[U-14C]glucose coinciding with stimulation of glycogenolysis. This unusual metabolic situation also coincided with a transient and paradoxical stimulation of insulin release in response to the decrease in extracellular D-glucose concentration. It is proposed, therefore, that the interference of glycogenolysis with glycolysis in pancreatic islets from glucose-infused rats participates in the paradoxical changes in insulin output which represent a typical feature of B-cell glucotoxicity. PMID- 8432853 TI - Variation in lipoprotein(a) concentrations among individuals with the same apolipoprotein (a) isoform is determined by the rate of lipoprotein(a) production. AB - Lipoprotein(a) [Lp(a)] is an atherogenic lipoprotein which is similar in structure to, but metabolically distinct from, LDL. Factors regulating plasma concentrations of Lp(a) are poorly understood. Apo(a), the protein that distinguishes Lp(a) from LDL, is highly polymorphic, and apo(a) size is inversely correlated with plasma Lp(a) level. Even within the same apo(a) isoform class, however, plasma Lp(a) concentrations vary widely. A series of in vivo kinetic studies were performed using purified radiolabeled Lp(a) in individuals with the same apo(a) isoform but different Lp(a) levels. In a group of seven subjects with a single S4-apo(a) isoform and Lp(a) levels ranging from 1 to 13.2 mg/dl, the fractional catabolic rate (FCR) of 131I-labeled S2-Lp(a) (mean 0.328 day-1) was not correlated with the plasma Lp(a) level (r = -0.346, P = 0.45). In two S4 apo(a) subjects with a 10-fold difference in Lp(a) level, the FCR's of 125I labeled S4-Lp(a) were very similar in both subjects and not substantially different from the FCRs of 131I-S2-Lp(a) in the same subjects. In four subjects with a single S2-apo(a) isoform and Lp(a) levels ranging from 9.4 to 91 mg/dl, Lp(a) concentration was highly correlated with Lp(a) production rate (r = 0.993, P = 0.007), but poorly correlated with Lp(a) FCR (mean 0.304 day-1). Analysis of Lp(a) kinetic parameters in all 11 subjects revealed no significant correlation of Lp(a) level with Lp(a) FCR (r = -0.53, P = 0.09) and a strong correlation with Lp(a) production rate (r = 0.99, P < 0.0001). We conclude that the substantial variation in Lp(a) levels among individuals with the same apo(a) phenotype is caused primarily by differences in Lp(a) production rate. PMID- 8432854 TI - Heterozygous lipoprotein lipase deficiency due to a missense mutation as the cause of impaired triglyceride tolerance with multiple lipoprotein abnormalities. AB - In 16 members of two Austrian families affected by a missense mutation at codon 188 of the lipoprotein lipase (LPL) gene (8 heterozygous and 8 normal subjects), carrier status for the mutation as determined by DNA analysis was related to LPL activity in postheparin plasma, to the magnitude of postprandial lipemia, and to concentration, composition, and size of the major lipoprotein classes of postabsorptive plasma. Carriers exhibited clearly reduced LPL activity, normal fasting triglycerides, but pronounced postprandial lipemia. The carriers' impaired triglyceride tolerance, as evident in the postprandial state of challenge only, was associated with a fasting lipoprotein constellation characterized by (a) enrichment of HDL2 with triglycerides, (b) reduced HDL2 cholesterol, (c) enrichment of VLDL and intermediate density lipoprotein (IDL) with cholesteryl esters, (d) elevated IDL levels, and (e) small-sized LDL. Within any given individual, the degrees of expression of these characteristics were quantitatively and continuously related with each other as well as with the magnitude of lipemia and with LPL activity. PMID- 8432855 TI - Time course and mechanism of oxidative stress and tissue damage in rat liver subjected to in vivo ischemia-reperfusion. AB - The time course of oxidative stress and tissue damage in zonal liver ischemia reperfusion in rat liver in vivo was evaluated. After 180 min of ischemia, surface chemiluminescence decreased to zero, state 3 mitochondrial respiration decreased by 70-80%, and xanthine oxidase activity increased by 26% without change in the water content and in the activities of superoxide dismutase, catalase, and glutathione peroxidase. After reperfusion, marked increases in oxyradical production and tissue damage were detected. Mitochondrial oxygen uptake in state 3 and respiratory control as well as the activities of superoxide dismutase, catalase, and glutathione peroxidase and the level of nonenzymatic antioxidants (evaluated by the hydroperoxide-initiated chemiluminescence) were decreased. The severity of the post-reperfusion changes correlated with the time of ischemia. Morphologically, hepatocytes appeared swollen with zonal cord disarrangement which ranged from mild to severe for the tissue reperfused after 60-180 min of ischemia. Neutrophil infiltration was observed after 180 min of ischemia and 30 min of reperfusion. Mitochondria appear as the major source of hydrogen peroxide in control and in reperfused liver, as indicated by the almost complete inhibition of hydrogen peroxide production exerted by the uncoupler carbonylcyanide p-(trifluoromethoxy) phenylhydrazone. Additionally, inhibition of mitochondrial electron transfer by antimycin in liver slices reproduced the inhibition of state 3 mitochondrial respiration and the increase in hydrogen peroxide steady-state concentration found in reperfused liver. Increased rates of oxyradical production by inhibited mitochondria appear as the initial cause of oxidative stress and liver damage during early reperfusion in rat liver. PMID- 8432856 TI - Tumor necrosis factor stimulates amino acid transport in plasma membrane vesicles from rat liver. AB - Severe infection is characterized by a translocation of amino acids from the periphery to the liver, an event that is mediated in part by cytokines such as tumor necrosis factor-alpha (TNF). We investigated the activities of Na(+) dependent transport systems A, ASC, and N in hepatic plasma membrane vesicles (HPMVs) prepared from rats treated with TNF in vivo. TNF did not alter sodium uptake but resulted in time- and dose-dependent fivefold and 50% maximal increases in system A and system N activity, respectively, in HPMVs secondary to an increase in the transport Vmax. Maximal increases in transport were observed 4 h after exposure to TNF and had returned to basal levels within 24 h. Similarly, system ASC activity was stimulated 80% in HPMVs from rats treated with TNF. Incubation of HPMVs from normal rats in vitro with TNF did not alter transport activity. Pretreatment of animals with the glucocorticoid receptor antagonist RU 38486 attenuated the TNF-induced enhancement in transport activity by 50%. The marked increase in Na(+)-dependent amino acid transport activity by TNF is mediated in part by the glucocorticoid hormones and represents an important mechanism underlying the accelerated hepatic amino acid uptake that occurs during critical illness. PMID- 8432857 TI - Characterization of cellular defects of insulin action in type 2 (non-insulin dependent) diabetes mellitus. AB - Seven non-insulin-dependent diabetes mellitus (NIDDM) patients participated in three clamp studies performed with [3-3H]- and [U-14C]glucose and indirect calorimetry: study I, euglycemic (5.2 +/- 0.1 mM) insulin (269 +/- 39 pM) clamp; study II, hyperglycemic (14.9 +/- 1.2 mM) insulin (259 +/- 19 pM) clamp; study III, euglycemic (5.5 +/- 0.3 mM) hyperinsulinemic (1650 +/- 529 pM) clamp. Seven control subjects received a euglycemic (5.1 +/- 0.2 mM) insulin (258 +/- 24 pM) clamp. Glycolysis and glucose oxidation were quantitated from the rate of appearance of 3H2O and 14CO2; glycogen synthesis was calculated as the difference between body glucose disposal and glycolysis. In study I, glucose uptake was decreased by 54% in NIDDM vs. controls. Glycolysis, glycogen synthesis, and glucose oxidation were reduced in NIDDM patients (P < 0.05-0.001). Nonoxidative glycolysis and lipid oxidation were higher. In studies II and III, glucose uptake in NIDDM was equal to controls (40.7 +/- 2.1 and 40.7 +/- 1.7 mumol/min.kg fat free mass, respectively). In study II, glycolysis, but not glucose oxidation, was normal (P < 0.01 vs. controls). Nonoxidative glycolysis remained higher (P < 0.05). Glycogen deposition increased (P < 0.05 vs. study I), and lipid oxidation remained higher (P < 0.01). In study III, hyperinsulinemia normalized glycogen formation, glycolysis, and lipid oxidation but did not normalize the elevated nonoxidative glycolysis or the decreased glucose oxidation. Lipid oxidation and glycolysis (r = -0.65; P < 0.01), and glucose oxidation (r = -0.75; P < 0.01) were inversely correlated. In conclusion, in NIDDM: (a) insulin resistance involves glycolysis, glycogen synthesis, and glucose oxidation; (b) hyperglycemia and hyperinsulinemia can normalize total body glucose uptake; (c) marked hyperinsulinemia normalizes glycogen synthesis and total flux through glycolysis, but does not restore a normal distribution between oxidation and nonoxidative glycolysis; (d) hyperglycemia cannot overcome the defects in glucose oxidation and nonoxidative glycolysis; (e) lipid oxidation is elevated and is suppressed only with hyperinsulinemia. PMID- 8432858 TI - Tolerance of rats to hyperoxia. Lung antioxidant enzyme gene expression. AB - Tolerance to hyperoxia usually requires an increase of lung antioxidant enzyme (AOE) activity. We used rats with different degrees of tolerance to > 95% O2 to evaluate the importance of individual AOEs for tolerance; we also explored the regulation of AOE gene expression. During exposure of adult rats to > 95% O2, lung manganese superoxide dismutase (MnSOD) activity fell approximately 50% despite a threefold increase of MnSOD mRNA concentration; addition of a reducing agent to lung extracts from O2-exposed rats partially restored MnSOD activity. Endotoxin induced tolerance to O2 (a) without elevating Cu,Zn superoxide dismutase activity, (b) with increases of catalase and glutathione peroxidase (GP) activity of the same magnitude as occurred in O2-saline rats, but (c) with MnSOD activity 1.5-1.9-fold higher than in air-saline rats and 1.4-3.6-fold higher than in O2-saline rats. Endotoxin elevated the concentration of MnSOD and GP mRNAs without increasing their stability. O2 elevated MnSOD mRNA concentration, and increased its stability. O2 plus endotoxin increased the concentration and stability of MnSOD, catalase, and GP mRNAs. These data suggest that in adult rats tolerance to hyperoxia requires increased MnSOD activity; the data show gene expression and regulation vary among the AOEs, and that increased stability of the AOEs' mRNAs plays an important role in AOE gene expression and in tolerance to hyperoxia. PMID- 8432859 TI - Abnormal regulation of ribosomal protein S6 kinase by insulin in skeletal muscle of insulin-resistant humans. AB - Insulin resistance in Pima Indians appears to result from a post-receptor impairment of insulin signal transduction that affects only some responses to insulin. To identify the primary lesion responsible for insulin resistance, we investigated the influence of insulin on ribosomal protein S6 kinase activities in skeletal muscle of insulin-sensitive and insulin-resistant nondiabetic Pima Indians during a 2-h hyperinsulinemic, euglycemic clamp. In sensitive subjects, S6 kinase activity was transiently activated fivefold over basal activity by 45 min of insulin infusion. Although basal activities in the two groups were similar, the response to insulin was delayed and restricted to about threefold over basal in subjects resistant to insulin. Two major S6 kinase activities in extracts of human muscle were resolved by chromatography on Mono Q. Peak 1, which accounted for basal activity owes to an enzyme antigenically related to the 90-kD S6 kinase II, a member of the rsk gene family. The major insulin-stimulated S6 kinase eluted as peak 2 and is antigenically related to a 70-kD S6 kinase. Our results show that insulin resistance impairs signaling to the 70-kD S6 kinase. PMID- 8432860 TI - Effect of insulin on system A amino acid transport in human skeletal muscle. AB - Transmembrane transport of neutral amino acids in skeletal muscle is mediated by at least four different systems (system A, ASC, L, and Nm), and may be an important target for insulin's effects on amino acid and protein metabolism. We have measured net amino acid exchanges and fractional rates of inward (k(in), min 1) and outward (kout, min-1) transmembrane transport of 2-methylaminoisobutyric acid (MeAIB, a nonmetabolizable amino acid analogue, specific for system A amino acid transport) in forearm deep tissues (skeletal muscle), by combining the forearm perfusion technique and a novel dual tracer ([1-H3]-D-mannitol and 2-[1 14C]-methylaminoisobutyric acid) approach for measuring in vivo the activity of system A amino acid transport. Seven healthy lean subjects were studied. After a baseline period, insulin was infused into the brachial artery to achieve local physiologic hyperinsulinemia (76 +/- 8 microU/ml vs 6.4 +/- 1.6 microU/ml in the basal period, P < 0.01) without affecting systemic hormone and substrate concentrations. Insulin switched forearm amino acid exchange from a net output ( 2,630 +/- 1,100 nmol/min per kig of forearm tissue) to a net uptake (1,610 +/- 600 nmol/min per kg, P < 0.01 vs baseline). Phenylalanine and tyrosine balances simultaneously shifted from a net output (-146 +/- 47 and -173 +/- 34 nmol/min per kg, respectively) to a zero balance (16.3 +/- 51 for phenylalanine and 15.5 +/- 14.3 nmol/min per kg for tyrosine, P < 0.01 vs baseline for both), showing that protein synthesis and breakdown were in equilibrium during hyperinsulinemia. Net negative balances of alanine, methionine, glycine, threonine and asparagine (typical substrates for system A amino acid transport) also were decreased by insulin, whereas serine (another substrate for system A transport) shifted from a zero balance to net uptake. Insulin increased k(in) of MeAIB from a basal value of 11.8.10(-2) +/- 1.7.10(-2).min-1 to 13.7.10(-2) +/- 2.2.10(-2).min-1 (P < 0.02 vs the postabsorptive value), whereas kout was unchanged. We conclude that physiologic hyperinsulinemia stimulates the activity of system A amino acid transport in human skeletal muscle, and that this effect may play a role in determining the overall concomitant response of muscle amino acid/protein metabolism to insulin. PMID- 8432861 TI - Characterization of apolipoprotein A-I- and A-II-containing lipoproteins in a new case of high density lipoprotein deficiency resembling Tangier disease and their effects on intracellular cholesterol efflux. AB - A 48-yr-old Caucasian female of central European origin (subject IM) with low plasma cholesterol and normal plasma triglyceride (TG) had extremely low apo A-I (6 mg/dl), A-II (5 mg/dl), and HDL cholesterol (2 mg/dl) levels. She had most of the clinical symptoms typically associated with Tangier disease, including early corneal opacities, yellow-streaked tonsils, hepatomegaly, and variable degrees of peripheral neuropathy, but had no splenomegaly. She had a myocardial infarction at age 46. Since HDL are postulated to be involved in the transport of excess cholesterol from peripheral tissues to the liver for degradation, and the ability of an HDL particle to promote cellular cholesterol efflux appears to be related to its density, size, and apo A-I and A-II contents, we isolated and characterized the HDL particles of this patient and all her first degree relatives (mother, a brother, and two children). The plasma A-I, A-II, and HDL cholesterol levels of all five relatives were either normal or high. Using anti-A I and anti-A-II immunosorbents, we found three populations of particles in IM: one contained both apo A-I and A-II, Lp(AI w AII); one contained apo A-I but no A II, Lp(AI w/o AII); and the third (an unusual one) contained apo A-II but no A-I, Lp(AII). Two-thirds of her plasma A-I and A-II existed in separate HDL particles, i.e., in Lp(AI w/o AII) and Lp(AII), respectively. Only Lp(AI w AII) and Lp(AI w/o AII) were present in the plasma of the relatives. All three populations of the patient's HDL particles had a normal core/surface lipid ratio, but the cores were enriched with TG. The apo A-I-containing particles, however, were considerably smaller and contained much less lipid than Lp(AII). Despite these unusual physicochemical characteristics, the apo A-I-containing particles and Lp(AII) were effective suppressors of intracellular cholesterol esterification in cholesterol-loaded human skin fibroblast. The patient's plasma apo D and lecithin cholesterol acyltransferase levels were reduced, with an increased proportion located in non-HDL plasma fractions. These findings are discussed in light of Tangier disease and other known HDL-deficiency cases, and the role of HDL in the maintenance of cell cholesterol homeostasis. PMID- 8432862 TI - Ontogeny of type 1 angiotensin II receptor gene expression in the rat. AB - To determine whether the expression of the type 1 angiotensin II receptor (AT1) gene is developmentally regulated and whether the regulation is tissue specific, AT1 mRNA levels were determined by Northern blot analysis in livers and kidneys from fetal, newborn, and adult rats, using a 1133-bp rat AT1 cDNA. In the liver, AT1 mRNA levels increased fivefold from 15 d gestation to 5 d of age. Liver AT1 mRNA levels at 5 d of age were similar to those of adult rats. In the kidney, AT1 mRNA levels were higher in immature than in adult animals. The intrarenal distribution of AT1 mRNA was assessed by in situ hybridization to a 35S-labeled 24 residues oligonucleotide complementary to rat AT1 mRNA. In the adult, AT1 mRNA was present in glomeruli, arteries, and vasa recta, whereas in the newborn AT1 mRNA was observed also over the nephrogenic area of the cortex. We conclude that: (a) fetal kidney and liver express the AT1 gene; (b) the AT1 gene expression is developmentally regulated in a tissue-specific manner; (c) during maturation, localization of AT1 mRNA in the kidney shifts from a widespread distribution in the nephrogenic cortex to specific sites in glomeruli, arteries, and vasa recta, suggesting a role for the angiotensin receptor in nephron growth and development. PMID- 8432863 TI - Agonist-mediated tissue factor expression in cultured vascular smooth muscle cells. Role of Ca2+ mobilization and protein kinase C activation. AB - Tissue factor (TF) is a low molecular weight glycoprotein that initiates the clotting cascade and is considered to be a major regulator of coagulation, hemostasis, and thrombosis. TF is not expressed in the intima or media of normal adult blood vessels. Accordingly, it has been hypothesized that the initiation of intravascular coagulation may require the "induced" expression of TF in the vessel wall. We report that TF mRNA and protein are rapidly and markedly induced in early and late passaged vascular smooth muscle cells (VSMC) by growth factors (serum, platelet-derived growth factor, epidermal growth factor), vasoactive agonists (angiotensin II), and a clotting factor (alpha-thrombin). The induction of TF mRNA by these agents is dependent upon mobilization of intracellular Ca2+ and is blocked by Ca2+ chelation. In contrast to other growth factor-responsive genes, such as KC and c-fos, downregulation of protein kinase C activity by prolonged treatment with phorbol esters fails to block agonist-mediated TF induction. This raises the possibility that protein kinase C activation may not be necessary for TF mRNA induction in VSMC. VSMC may play a role in the generation or propagation of thrombus through the induction of TF, particularly in settings, such as those associated with acute vessel injury, where the endothelium is denuded and the VSMC are exposed to circulating blood. PMID- 8432864 TI - Neointimal macrophages colocalize with extracellular matrix gene expression in human atherosclerotic pulmonary arteries. AB - Vascular remodeling in adult atherosclerotic pulmonary arteries is characterized by discrete areas of neointimal extracellular matrix gene expression, suggesting regulation by local factors. Though the factors responsible for inducing matrix gene expression in atherosclerotic lesions are largely unknown, several observations suggest macrophages may be a focal source of those factors. Immunohistochemistry confirmed the presence of macrophages in the neointima of atherosclerotic elastic pulmonary arteries from patients with unexplained pulmonary hypertension. Areas of neointima containing dense clusters of macrophages were separated by sparsely populated areas. Foamy macrophages resided more deeply within the neointima than nonfoamy macrophages, which were found more often subjacent to the endothelium or within the lumenal one-third of the neointima. Combined immunohistochemistry-in situ hybridization indicated neointimal fibronectin and type I procollagen gene expression was intimately associated only with nonfoamy neointimal macrophages. These observations suggest that: (a) nonfoamy neointimal macrophages participate in the local regulation of extracellular matrix gene expression in atherosclerotic pulmonary arteries; (b) foamy macrophages, which are not associated with matrix gene expression, have undergone modulation of their secretory phenotype. PMID- 8432865 TI - Intravenous immunoglobulin contains specific antibodies inhibitory to activation of T cells by staphylococcal toxin superantigens [see comment]. AB - Superantigens are products of bacteria with dual affinity for HLA-DR and the variable region of the beta chain of the T cell receptor, leading to the stimulation of large numbers of T cells. Because there is evidence for the involvement of superantigens in various disease conditions in which intravenous IgG (IVIgG) is used as therapy, the purpose of the present study was to determine if IVIgG contains antibodies inhibitory to T cell stimulation by the superantigens. ELISA and Western assays revealed high concentrations of antibodies in the pooled IgG against eight different staphylococcal toxin (Staph toxin) superantigens. The IVIgG inhibited in vitro stimulation of human peripheral blood T cells by the Staph-toxins, but did not inhibit responses elicited by phytohemagglutinin or anti-CD3. Inhibition was mediated by Staph toxin-specific antibodies as shown by affinity adsorption depletion studies. The antibodies functioned by inhibiting the binding and/or presentation of Staph toxins by DR+ accessory cells. In conclusion, this report is the first to show that normal pooled IgG contains antibodies against a major group of the superantigens, the Staph-toxins, and that the antibodies can inhibit Staph-toxin elicited T cell activation, suggesting a possible immunoregulatory role for the antibodies in vivo. PMID- 8432866 TI - Influence of the high-affinity growth hormone (GH)-binding protein on plasma profiles of free and bound GH and on the apparent half-life of GH. Modeling analysis and clinical applications. AB - The discovery of a specific high-affinity growth hormone (GH) binding protein (GH BP) in plasma adds complexity to the dynamics of GH secretion and clearance. Intuitive predictions are that such a protein would damp sharp oscillations in GH concentrations otherwise caused by bursts of GH secretion into the blood volume, prolong the apparent half-life of circulating GH, and contribute a reservoir function. To test these implicit considerations, we formulated an explicit mathematical model of pulsatile GH secretion and clearance in the presence of absence of a specific high-affinity GH-BP. Simulation experiments revealed that the pulsatile mode of physiological GH secretion creates a highly dynamic (nonequilibrium) system, in which the half-life of free GH, its instantaneous secretion rate, and the GH-BP affinity and capacity all contribute to defining momentary levels of free, bound, and total GH, the percentage of GH bound to protein, and the percentage occupancy of GH-BP [corrected]. In contrast, the amount of free GH at equilibrium is specified only by the GH distribution volume and secretion rate and the half-life of free hormone. We conclude that the in vivo dynamics of GH secretion, trapping, and clearance from the circulation offer a variety of regulatory loci at which the time structure of free, bound, and total GH delivery to target tissues can be controlled physiologically. PMID- 8432867 TI - Effects of oleate-rich and linoleate-rich diets on the susceptibility of low density lipoprotein to oxidative modification in mildly hypercholesterolemic subjects. AB - We report the results of feeding oleate- or linoleate-enriched diets for 8 wk to mildly hypercholesterolemic subjects and the resulting alterations in composition and functional properties of their plasma LDL and HDL. LDL isolated from subjects on oleate-enriched diets was less susceptible to copper-mediated oxidation, as measured by conjugated diene and lipid peroxide formation, and less susceptible to LDL-protein modification, as evidenced by reduced LDL macrophage degradation after copper- or endothelial cell-induced oxidation. For all subjects, the percentage of 18:2 in LDL correlated strongly with the extent of conjugated diene formation (r = 0.89, P < 0.01) and macrophage degradation (r = 0.71, P < 0.01). Oxidation of LDL led to initial rapid depletion of unsaturated fatty acids in phospholipids followed by extensive loss of unsaturated fatty acids in cholesteryl esters and triglycerides. Changes in HDL fatty acid composition also occurred. However, HDL from both dietary groups retained its ability to inhibit oxidative modification of LDL. This study demonstrates that alterations in dietary fatty acid composition can effectively alter the fatty acid distribution of LDL and HDL in hypercholesterolemic subjects and that susceptibility to LDL oxidation is altered by these changes. Substitution of monounsaturated (rather than polyunsaturated) fatty acids for saturated fatty acids in the diet might be preferable for the prevention of atherosclerosis. PMID- 8432868 TI - Genetic and phenotypic heterogeneity in familial lecithin: cholesterol acyltransferase (LCAT) deficiency. Six newly identified defective alleles further contribute to the structural heterogeneity in this disease. AB - The presence of lecithin:cholesterol acyltransferase (LCAT) deficiency in six probands from five families originating from four different countries was confirmed by the absence or near absence of LCAT activity. Also, other invariate symptoms of LCAT deficiency, a significant increase of unesterified cholesterol in plasma lipoproteins and the reduction of plasma HDL-cholesterol to levels below one-tenth of normal, were present in all probands. In the probands from two families, no mass was detectable, while in others reduced amounts of LCAT mass indicated the presence of a functionally inactive protein. Sequence analysis identified homozygous missense or nonsense mutations in four probands. Two probands from one family both were found to be compound heterozygotes for a missense mutation and for a single base insertion causing a reading frame-shift. Subsequent family analyses were carried out using mutagenic primers for carrier identification. LCAT activity and LCAT mass in 23 genotypic heterozygotes were approximately half normal and clearly distinct from those of 20 unaffected family members. In the homozygous patients no obvious relationship between residual LCAT activity and the clinical phenotype was seen. The observation that the molecular defects in LCAT deficiency are dispersed in different regions of the enzyme suggests the existence of several functionally important structural domains in this enzyme. PMID- 8432869 TI - Lack of HLA class I antigen expression by melanoma cells SK-MEL-33 caused by a reading frameshift in beta 2-microglobulin messenger RNA. AB - The lack of HLA class I antigen expression by the melanoma cell line SK-MEL-33 is caused by a unique lesion in beta 2-microglobulin (beta 2-mu). Sequencing of beta 2-mu mRNA detected a guanosine deletion at position 323 in codon 76 that causes a frameshift with a subsequent introduction of a stop codon at a position 54 base upstream of the normal position of the stop codon in the message. The loss of 18 amino acids and the change of 6 amino acids, including a cysteine at position 80 in the carboxy terminus of beta 2-mu, are likely to cause marked changes in the structure of the polypeptide. The latter may account for the inability of beta 2 mu to associate with HLA class I heavy chains and for its lack of reactivity with the anti-beta 2-mu mAb tested. HLA class I antigen expression on SK-MEL-33 cells was reconstituted after transfection with a wild-type B2m gene, therefore indicating that the abnormality of endogenous B2m gene is the only mechanism underlying lack of HLA class I antigen expression by SK-MEL-33 cells. The guanosine deletion in B2m gene was detected also in the melanoma tissue from which SK-MEL-33 cells had originated. Therefore, the molecular lesion identified in the SK-MEL-33 melanoma cell line is not caused by a mutation acquired during growth in vitro but is likely to reflect a somatic mutation during tumor progression. PMID- 8432870 TI - Inorganic iron effects on in vitro hypoxic proximal renal tubular cell injury. AB - Iron-dependent free radical reactions and renal ischemia are believed to be critical mediators of myohemoglobinuric acute renal failure. Thus, this study assessed whether catalytic iron exacerbates O2 deprivation-induced proximal tubular injury, thereby providing an insight into this form of renal failure. Isolated rat proximal tubular segments (PTS) were subjected to either hypoxia/reoxygenation (H/R: 27:15 min), "chemical anoxia" (antimycin A; 7.5 microM x 45 min), or continuous oxygenated incubation +/- ferrous (Fe2+) or ferric (Fe3+) iron addition. Cell injury (% lactic dehydrogenase [LDH] release), lipid peroxidation (malondialdehyde, [MDA]), and ATP depletion were assessed. Under oxygenated conditions, Fe2+ and Fe3+ each raised MDA (approximately 7-10x) and decreased ATP (approximately 25%). Fe2+, but not Fe3+, caused LDH release (31 +/- 2%). During hypoxia, Fe2+ and Fe3+ worsened ATP depletion; however, each decreased LDH release (approximately 31 to approximately 22%; P < 0.01). Fe(2+) mediated protection was negated during reoxygenation because Fe2+ exerted its intrinsic cytotoxic effect (LDH release: Fe2+ alone, 31 +/- 2%; H/R 36 +/- 2%; H/R + Fe2+, 41 +/- 2%). However, Fe(3+)-mediated protection persisted throughout reoxygenation because it induced no direct cytotoxicity (H/R, 39 +/- 2%; H/R + Fe3+, 25 +/- 2%; P < 0.002). Fe3+ also decreased antimycin toxicity (41 +/- 4 vs. 25 +/- 3%; P < 0.001) despite inducing marked lipid peroxidation and without affecting ATP. These results indicate that catalytic iron can mitigate, rather than exacerbate, O2 deprivation/reoxygenation PTS injury. PMID- 8432871 TI - Transgenic mice expressing a partially deleted gene for type I procollagen (COL1A1). A breeding line with a phenotype of spontaneous fractures and decreased bone collagen and mineral. AB - A line of transgenic mice was prepared that expressed moderate levels of an internally deleted human gene for the pro alpha 1(I) chain of type I procollagen. The gene construct was modeled after a sporadic in-frame deletion of the human gene that produced a lethal variant of osteogenesis imperfecta by causing biosynthesis of shortened pro alpha 1(I) chains. 89 transgenic mice from the line were examined. About 6% had a lethal phenotype with extensive fractures at birth, and 33% had fractures but were viable. The remaining 61% of the transgenic mice had no apparent fractures as assessed by x ray examination on the day of birth. Brother-sister matings produced eight litters in which approximately 40% of the mice had the lethal phenotype, an observation indicating that expression of the exogenous gene was more lethal in putative homozygous mice from the line. Examination of femurs from the transgenic mice indicated that the bones were significantly shorter in length and had a decrease in wet weight, mineral content, and collagen content. However, there was no statistically significant change in the mineral to collagen ratio. Biomechanical measurements on femurs from the mice at 6 wk indicated a decrease in force and energy to failure. There was also a decrease in strain to failure and an increase in Young's modulus of elasticity, observations indicating increased brittleness of bone matrix. The results suggested that the transgenic mice may be an appropriate model for testing potential therapies for osteogenesis imperfecta. They may also be a useful model for studying osteoporosis. PMID- 8432872 TI - Major cytoplasmic membrane protein of Legionella pneumophila, a genus common antigen and member of the hsp 60 family of heat shock proteins, induces protective immunity in a guinea pig model of Legionnaires' disease. AB - We have examined the capacity of the major cytoplasmic membrane protein (MCMP) of Legionella pneumophila, a genus common antigen and member of the hsp 60 family of heat shock proteins, to induce protective immunity in a guinea pig model of Legionnaires' disease. We purified MCMP to homogeneity from L. pneumophila by buffer extraction, ion-exchange chromatography, and molecular sieve chromatography. Guinea pigs immunized with MCMP developed a strong cell-mediated immune response to the immunogen manifest by marked cutaneous delayed-type hypersensitivity. Guinea pigs immunized with MCMP and then challenged with a lethal aerosol dose of L. pneumophila exhibited a high level of protective immunity. Altogether, in four independent experiments, 55 of 64 (86%) animals immunized three times with 0.6-40 micrograms MCMP including 11 of 11 (100%) animals immunized three times with 40 micrograms MCMP survived aerosol challenge with L. pneumophila compared with 1 of 29 (3%) sham-immunized control animals (P < 0.0001, Cochran-Mantel-Haenszel X2 statistic for pooled data). To our knowledge, MCMP is the first member of the hsp 60 family of proteins shown to induce protective immunity to a microbial pathogen. MCMP has potential as a vaccine against Legionnaires' disease. Since MCMP is a genus common antigen, vaccination with a combination of MCMPs derived from different Legionella species has the potential of inducing protective immunity against all the major Legionella species causing human disease. PMID- 8432873 TI - Prevention of smooth muscle cell outgrowth from human atherosclerotic plaque by a recombinant cytotoxin specific for the epidermal growth factor receptor. AB - Smooth muscle cell proliferation in the intima of arteries is a principal event associated with vascular narrowing after balloon angioplasty and bypass surgery. Techniques for limiting smooth muscle cell proliferation, however, have not as yet yielded any therapeutic benefit for these conditions. This may reflect the present lack of sufficiently potent and specific inhibitors of smooth muscle cell proliferation. DAB389 EGF is a genetically engineered fusion protein in which the receptor-binding domain of diphtheria toxin has been replaced by human epidermal growth factor. We evaluated the effect of this fusion toxin on human vascular smooth muscle cells in culture. Incubation of proliferating cells with DAB389 EGF yielded a dose-dependent inhibition of protein synthesis, as assessed by uptake of [3H]leucine, with an IC50 of 40 pM. The cytotoxic effect was inhibited in the presence of excess EGF or with monoclonal antibody to the EGF receptor. We further studied the effect of the fusion toxin on smooth muscle cell outgrowth from human atherosclerotic plaque. Outgrowth was markedly inhibited after as little as 1 h of exposure to the fusion protein. Furthermore, complete inhibition of proliferation of cells within the plaque could be attained. These results demonstrate that DAB389 EGF is highly cytotoxic to human smooth muscle cells proliferating in culture and can prevent smooth muscle cell outgrowth from "growth-stimulated" human atherosclerotic plaque. DAB389 EGF may therefore be of therapeutic value in vascular diseases characterized by smooth muscle cell accumulation. PMID- 8432874 TI - Effects of parental adjustment on the adaptation of children with congenital or acquired limb deficiencies. AB - Maternal and paternal depression, anxiety, and marital discord were investigated as predictors of depression, anxiety, and self-esteem in 54 children with congenital or acquired limb deficiencies. Higher paternal depression predicted higher child depression and higher anxiety. Higher paternal anxiety predicted higher child depression and anxiety and lower self-esteem. Higher marital discord predicted higher child depression and anxiety and lower self-esteem. Maternal depression and anxiety did not predict child psychological adaptation. Family support had a positive effect on child adaptation, as did parent, classmate, teacher, and friend social support. The findings are discussed in terms of the risk and protective effects of parental distress, marital discord, and social support on the psychological adaptation of children with visible chronic physical disorders. J Dev Behav Pediatr 14:13-20, 1993. Index terms: limb deficiencies, children, adjustment, social support, parental distress, family functioning, marital discord. PMID- 8432875 TI - Language development in low birth weight infants: the first two years of life. AB - The four main aims of this cohort study were to (1) determine the number of consecutively referred low birth weight (LBW) infants presenting with delayed language at 12 and 24 months of age, (2) examine language profiles by measuring both functional and spontaneous language ability in 24-month-olds, (3) examine the relationship between perinatal medical history and language status at 12 and 24 months, and (4) examine the clinical validity of the Early Language Milestone (ELM) scale, a brief language screening instrument. Only infants without serious sensory impairment or mental handicap were included in the final sample. Seventy one LBW infants (36 12-month-olds, 35 24-month-olds) were seen for developmental and language assessments. The findings suggest that within the first 2 years of life, low to moderate rates of language delay are evident in LBW infants who have already been screened for serious sensory or mental handicap. At 12 months of age, 8.3% of the infants had delayed expressive language; none had delayed receptive language. At 24 months of age, 28% of the infants had delayed expressive language; 5.7% had delayed receptive language. Furthermore, only 32% of those with normal expressive language and sufficient language sample had a mean length of response within the normal range. Language status was not related to a specific perinatal medical variable. Additional study into the clinical validity of the ELM as a screening measure for the LBW population is warranted. The ELM specificity for both receptive and expressive language domains was good at both ages (80 to 100%), but sensitivity was low to moderate (0 to 68%). PMID- 8432876 TI - Research on children's behavior after hospitalization: a review and synthesis. AB - Despite the presence of considerable research on techniques for reducing distress associated with childhood hospitalization, few studies have examined the more basic issue of whether the event negatively affects children after discharge. A meta-analysis was conducted of studies using the Posthospital Behavior Questionnaire (the most commonly used method of examining posthospital behavior) to determine whether hospitalization results in negative behavioral change, the duration of this reaction, if detected, and factors potentially related to its strength. The mean weighted effect size was +.29 (Confidence interval .95 = +/- .07). Thus, in the absence of interventions, negative behavior tends to increase significantly after discharge (z = +3.99; p < .00006). However, this response diminishes with time and has largely disappeared after 2 weeks. Contrary to expectations, neither age of subjects nor their medical condition was related to their degree of upset. Subjects hospitalized for periods of 2 to 3 days exhibited more behavioral distress than did those hospitalized for either shorter or longer periods. PMID- 8432877 TI - Research on the effect of experimental interventions on children's behavior after hospitalization: a review and synthesis. AB - Despite continued interest in ameliorating the posthospital psychological effects of hospitalization on children, there have been no analytic reviews of the research on this topic. The present study synthesized all known research that evaluated experimental interventions through the use of the Posthospital Behavior Questionnaire (PHBQ), by far the most commonly used method of examining posthospital behavior. The mean weighted effect size (ES) was +.44, Confidence Interval (CI).95 = +/- .10. Thus, on the average, children who received experimental interventions tended to change their behavior in the direction of psychological upset less than children who did not (z = +4.81; p < .00006). Analyses of ES moderators indicated significant variations (p < .05) associated with (1) the year of the report, (2) questionnaire format, (3) study design, (4) variations in experimental treatment, (5) subject's age, and (6) length of hospitalization. Psychoeducational preparation was not effective with younger children. The benefits of experimental interventions persisted up to 4 weeks after discharge. PMID- 8432878 TI - Children and hospitalization: putting the new reviews in methodological context. PMID- 8432879 TI - Children in hospitals. PMID- 8432880 TI - Recurrent otitis media and parenting stress in mothers of two-year-old children. PMID- 8432881 TI - Child, parent, and physician perceived satisfaction with pediatric outpatient visits. AB - Patient satisfaction has been linked empirically to a variety of health care outcomes (e.g., treatment adherence). Unfortunately, there is a paucity of data regarding the assessment of children's satisfaction with pediatric care. This lack of instrumentation was the impetus for the development and preliminary validation of the Metro Assessment of Child Satisfaction (MACS). Findings indicated the MACS is internally consistent and easily administered and understood by children as young as 6 years of age. Factor analysis yielded four distinct factors that appear to be statistically valid and clinically meaningful. Findings are discussed in relation to maternal ratings of satisfaction and physician perceptions of patient and parent satisfaction. PMID- 8432882 TI - ACP Broadsheet 135: January 1993. Isolation and identification methods for Escherichia coli O157 and other Vero cytotoxin producing strains. PMID- 8432884 TI - Guidelines for screening for Cryptosporidium in stools: report of a joint working group. PMID- 8432883 TI - Cathepsin B expression in tumour cells and laminin distribution in pulmonary adenocarcinoma. AB - AIMS: To determine the correlation between cathepsin B expression and laminin distribution in pulmonary adenocarcinoma tissue. METHODS: The distribution of cathepsin B and laminin was examined in 28 formalin fixed, paraffin wax embedded specimens of pulmonary adenocarcinoma tissue, using a double immunostaining technique with commercially available antibodies to cathepsin B and laminin, respectively. RESULTS: Tumour cells in 23 (82%) cases reacted to cathepsin B: 13 cases were weakly positive and 10 were strongly positive. Laminin in tumour associated basement membrane produced various staining patterns: two cases had an almost continuous distribution of laminin in tumour associated basement membrane in the tumour tissues, while a moderately discontinuous laminin distribution pattern was found in 12 cases, and a highly fragmented pattern was found in 14 cases. The degree of cathepsin B expression in tumour cells was significantly correlated with the break up of laminin staining. In some cases a discontinuous pattern of tumour associated laminin was frequently observed adjacent to cathepsin B positive tumour cell nests. CONCLUSIONS: Considering that cathepsin B has the capacity to degrade basement membrane components, including laminin, the inverse correlation shown in this study between the increase in cathepsin B expression by tumour cells and the diminution of laminin in tumour associated basement membrane could reflect local progression and spread by pulmonary adenocarcinoma. PMID- 8432885 TI - Intramural platelet deposition in cerebral vasculopathy of systemic lupus erythematosus. AB - AIMS: To test the hypothesis that fragments of platelet thrombi and vascular endothelium are incorporated into the walls of small cerebral vessels in systemic lupus erythematosus (SLE). METHODS: Six varied necropsy cases of central nervous system (CNS) SLE and 15 controls were studied. The controls were selected to represent a wide range of diseases in which the cerebral circulation is compromised. Tissue sections were stained by standard histochemical and immunocytochemical methods, the latter using antibodies to platelet membrane glycoprotein IIIa (CD61), and vascular endothelium (CD31). RESULTS: In four of six cases of CNS SLE characterised by small vessel hyalinization and thickening, fragments of platelet membrane were found in the walls of small cortical and meningeal vessels. Similar findings were not evident in two other SLE cases that were characterised by relatively short clinical histories and an acute vasculitis. One control case of severe polyarteritis nodosa showed platelet fragment deposition in arteries larger than the vessels so affected in SLE. CONCLUSIONS: Previous studies have suggested that neuropsychiatric symptoms in SLE may be related to repeated episodes of vasculitis in small cerebral vessels that are triggered by antiphospholipid antibodies. Concurrent thrombus formation might facilitate the incorporation of platelet fragments into small vessel walls. This process contributes to the thickening and irregularity of small vessels, a major feature of longstanding cases of CNS SLE. PMID- 8432886 TI - Effects of azathioprine on response of renal anaemia to subcutaneous recombinant human erythropoietin. AB - AIMS: To determine the effect of concomitant azathioprine treatment on the response of patients with renal failure to treatment with subcutaneous recombinant human erythropoietin (r-HuEPO). METHODS: Two groups of patients with renal failure not receiving haemodialysis were studied. One comprised seven patients receiving erythropoietin alone, the second consisted of nine patients who were also treated with azathioprine. The haematological changes were monitored, and the functional erythropoietic response was studied by two different ferrokinetic models. One analysed the initial, the other the extended plasma iron clearance. Studies were performed before r-HuEPO treatment on all 16 patients, and repeated on 11 of these when the target haemoglobin (10-11 g/dl) was achieved and stabilised. Total erythropoiesis was determined using both techniques. Analysis of the extended plasma iron clearance also permitted calculation of both effective and ineffective erythroid activity. RESULTS: The haematological response to r-HuEPO was the same for both patient groups. Measurement of total erythropoiesis by both ferrokinetic methods showed good correlation. For those receiving long term azathioprine, the percentage ineffective erythropoiesis was high compared with that of the other patients, and remained so for as long as they continued with azathioprine. For those uncomplicated by azathioprine treatment, r-HuEPO increased levels of both effective and ineffective erythropoiesis by the same degree. A substantial reduction in ineffective erythropoiesis was shown only by those patients who either discontinued or reduced their azathioprine once they started r-HuEPO treatment. CONCLUSIONS: Azathioprine increases ineffective erythropoiesis. In this study, the r-HuEPO dose was sufficient to overcome this effect and promoted effective erythropoiesis so that the anaemia lessened. Measurement of total erythropoiesis provided limited information on the functional changes involved, differentiation of effective from ineffective erythropoiesis being necessary to define the changes after azathioprine reduction or withdrawal. PMID- 8432887 TI - High incidence of type II autoantibodies in pernicious anaemia. AB - AIMS: To investigate the incidence of type II autoantibodies to intrinsic factor in pernicious anaemia. METHODS: Three hundred and forty four serum samples submitted for intrinsic factor antibody (IFAB) analysis on clinical or laboratory grounds were tested by an established radioassay and a new enzyme linked immunosorbent assay (ELISA) method for type I and total IFAB, respectively. Sixty of these were found to be positive by ELISA; this method was used to test further, 40 samples of adequate volume for types I and II antibodies. RESULTS: Type II antibodies were detected in 39 of the 40 sera tested. A comparative analysis indicated that seven samples contained pure type II antibody, being positive for total and type II by ELISA, but negative for type I by both the ELISA and radioassay technique. CONCLUSIONS: The occurrence of type II antibody, both alone and in combination with type I, seems to be more common than has previously been recognised, and emphasises the advantage of using a technique which will detect both types of antibody. PMID- 8432888 TI - Out of Africa: observations on the histopathology of Mycobacterium ulcerans infection. PMID- 8432889 TI - Histopathological findings in oesophageal carcinoma with and without preoperative chemotherapy. AB - AIMS: To investigate the pathological effects of preoperative chemotherapy on oesophageal carcinoma. METHODS: Qualitative and quantitative changes in oesophageal carcinoma after preoperative chemotherapy were assessed by examination of biopsy specimens before treatment and resected specimens. RESULTS: Of 13 patients with adenocarcinoma treated with 5-fluorouracil, adriamycin, and mitomycin (FAM), nine showed minor histological changes compared with 14 control cases. All 12 patients with squamous carcinoma treated with preoperative mitomycin, ifosfamide, and cisplatin (MIC) showed noticeable histological changes when compared with the 13 control cases. Changes included complete ablation (n = 1) and partial regression (n = 5) of the tumour. A quantitative estimate of the proportion of tumour to stroma showed no difference between control adenocarcinomas and those treated with chemotherapy. There was, however, a significant reduction (p < 0.01) in the proportion of tumour to stroma in the treated squamous group compared with the controls. There was no relation between the degree of response in squamous carcinomas and the degree of differentiation of the tumour. Patients in which squamous carcinomas responded well, as assessed quantitatively, showed a tendency to better survival at one year. CONCLUSIONS: Histopathological changes attributable to chemotherapy can be observed in oesophageal carcinoma. The response of squamous carcinoma to MIC is histologically more evident than that of adenocarcinoma to FAM. A quantitative technique may be useful in assessing the effect of chemotherapy in oesophageal squamous carcinoma. PMID- 8432890 TI - Inverted hyperplastic polyposis of the colon. AB - AIMS: To describe and evaluate two apparently unique cases of inverted hyperplastic (metaplastic) polyposis of the colon. METHODS: The cases were analysed by standard histopathological, histochemical, and immunohistochemical techniques and the findings compared with those of regular hyperplastic polyps of the colorectum. RESULTS: Both patients were middle-aged men with concurrent adenocarcinoma of the proximal large intestine. The inverted polyps numbered 18 and 12, measured between 0.4 and 2.5 cm in diameter, and all were present in the proximal ascending colon. The polyps had characteristic macroscopic features: they were positioned on the apex of mucosal folds and demonstrated surface pitting and mucus hypersecretion. Histologically, inversion and misplacement of hyperplastic epithelium was related to lymphoglandular complexes. The polyps showed all the histochemical and immunohistochemical features of regular hyperplastic polyps. CONCLUSIONS: Inverted hyperplastic polyps are an unusual but distinctive polyp of the proximal colon, may be multiple, and share the phenotypic changes of regular hyperplastic polyps. The pathogenesis of epithelial inversion probably relates to misplacement of epithelium through anatomical defects in the muscularis mucosae due to mechanical forces. The polyps may mimic both adenomas and carcinomas. The neoplastic potential of inverted hyperplastic polyposis is likely to be very low: one polyp only showed adenomatous change. PMID- 8432891 TI - What is marrow fibrosis after treatment of neuroblastoma? AB - AIMS: To test the hypothesis that the abnormal fibrous stroma of bone marrow found after treatment of disseminated neuroblastoma represents traumatic scarring. METHODS: Twenty six restaging bone marrow biopsy specimens from 14 children with disseminated neuroblastoma were compared with 37 from 37 children with acute lymphoblastic leukaemia. They were assessed independently by two observers for the presence of abnormal fibrous stroma. All biopsies were performed 23 to 50 days after the initial diagnostic biopsy, and from the same iliac crest. A further nine restaging bone marrow biopsy specimens from previously unbiopsied iliac crests from four children with neuroblastoma were examined and the appearances of the diagnostic bone marrow specimens in those with neuroblastoma recorded. Between diagnostic and restaging biopsies, the children received combination chemotherapy regimens. RESULTS: In neuroblastoma abnormal stromal material was observed in 17 of 26 rebiopsied iliac crests as opposed to only 9 of 37 of those with acute lymphoblastic leukaemia (p < 0.005). In addition, four of nine restaging biopsy specimens taken from previously unbiopsied crests in patients with neuroblastoma contained abnormal stroma. All 11 children with neuroblastoma whose restaging specimens contained abnormal stroma had similar abnormalities in one or more biopsy specimens at diagnosis. CONCLUSIONS: Abnormal fibrous stromal material in restaging marrow biopsy specimens of previously biopsied iliac crests occurs much more frequently in neuroblastoma than in acute lymphoblastic leukaemia. We suggest that factors other than traumatic scarring are responsible. This is supported by finding similar abnormalities in previously unbiopsied iliac crests and in the diagnostic biopsy specimens of children with neuroblastoma. PMID- 8432892 TI - Effect of the choice of WHO International Reference Preparation for thromboplastin on International Normalised Ratios. AB - AIMS: To compare the International Normalised Ratio (INR) obtained directly with the two types of WHO plain International Reference Preparation for thromboplastin in patients treated with coumarin. METHODS: Prothrombin times were performed in parallel at four centres using WHO human plain IRP (BCT/253) and rabbit plain IRP (RBT/79). Sixty patients and 20 normal controls were tested at each centre. Differences in INR among the centres were assessed by one factor, analysis of variance. The bias for each centre was assessed by the t test. RESULTS: At all four centres higher INRs were consistently found with the rabbit plain reagent. Two of the centres showed significantly greater bias. CONCLUSIONS: There was a small but significant difference in INR results obtained directly with these two reference reagents at all four centres (mean 7.35%). This in part may result from the different responsiveness of the two IRP to the coumarin defect or to imprecision of the original ISI calibrations of the two plain WHO IRP. The findings support the adoption of a single master IRP, in accord with WHO recommendations, which would resolve the present anomalous situation. PMID- 8432893 TI - Audit of start of anticoagulation treatment in inpatients. AB - AIMS: To develop a method for evaluating the start of anticoagulation treatment in inpatients. METHODS: One hundred case notes were audited using a proforma based on local guidelines in accordance with British Society for Haematology recommendations. RESULTS: Confirmatory investigations were done in 93% and 79% of patients with symptomatic deep venous thrombosis and pulmonary embolism, respectively. Identification of patients' risk factors for anticoagulation by history taking and laboratory tests was often inadequate: baseline coagulation screen, platelet count, liver function and renal function tests were done in 52%, 95%, 70% and 87% of cases, respectively. There was a tendency to undertreat patients: 33% of the activated partial thromboplastin times (APTT) and 58% of the International Normalised Ratios (INR) were subtherapeutic. The heparin-warfarin crossover period was particularly problematic: 37% stopped heparin without an INR that day, or had an INR of less than 2. Microscopic haematuria was monitored occasionally. Of the 62 patients continuing anticoagulation, 72% were discharged with the final INR in the therapeutic range. At discharge, only 74% of patients had documented appointments for the anticoagulant Clinic, the period between discharge and appointment ranging from 0 to 12 days. Of the 25 cases with an appointment exceeding four days after discharge, only six (24%) had arrangements for an interim INR check. CONCLUSIONS: The experience allowed the proforma to become streamlined to a more practical, reliable, and valid tool for use elsewhere. Findings will be fed back to the hospital staff to promote practice improvements before closing the audit loop by re-evaluating practice. Further studies are in progress to identify barriers experienced by doctors in implementing the guidelines and problems in the process of referral to the anticoagulant clinic. PMID- 8432894 TI - Foreign body giant cell reactions and ossification associated with benign melanocytic naevi. AB - AIMS: To assess the incidence of foreign body giant cell reactions and ossification in benign/melanocytic naevi; and to examine their pathological features to gain an insight into their pathogenesis. METHODS: Intradermal (n = 185) and compound naevi (n = 110) from a routine histology service, together with 60 naevi submitted to an ophthalmic pathologist, were examined for foreign body reactions and ossification. Additional cases were identified prospectively in the course of routine reporting. The clinical and pathological features of positive cases were assessed. RESULTS: Foreign body reactions were identified in nine (4.9%) intradermal and four (3.6%) compound naevi, but in none of the naevi from around the eye. One intradermal naevus showed ossification. A further 11 naevi showing foreign body reaction and five showing ossification alone were identified prospectively. The 24 naevi showing a foreign body reaction had a similar age and sex distribution to controls but were more likely to occur on the head and neck. The reaction usually occurred deep to the naevus, sometimes in relation to a hair follicle, and fragments of hair or keratin were identified in most. Osteoid or bone was present within the reaction in five. In six other naevi, all from the head and neck of women, osteoid or mature bone was present deep to the naevus in the absence of a giant cell reaction. CONCLUSIONS: Foreign body giant cell reactions occur not uncommonly in relation to benign naevi, as a result of follicular damage, possibly due to trauma. The similar siting of foci of bone suggests that ossification occurs as a secondary phenomenon in these cases. PMID- 8432895 TI - Ammonium metabolism and protection from urease mediated destruction in Helicobacter pylori infection. AB - AIM: To investigate further the intracellular ammonium metabolism of Helicobacter pylori and the mechanism of its urease mediated destruction. METHODS: The mechanism of the in vitro destruction of H pylori was investigated by incubating it in buffer solutions, at pH 6.0, containing isocitrate or alpha ketoglutarate in addition to urea concentrations which had previously been shown to destroy H pylori. RESULTS: The median (range) 5 minute survival of H pylori in 0.2 mol/l citrate buffer (pH 6.0) in the absence of urea was 88% (18-184%) and was similar to its survival in 0.2 mol/l isocitrate buffer in the absence of urea, median 88% (15-274%). In the presence of 50 mmol/l urea the survival of H pylori in the citrate buffer was reduced, 9.9% (0-146%), compared with its survival in isocitrate buffer with the same concentration of urea 37% (0-274%) (p < 0.01). A 72 hour preincubation of the organism with 10 mmol/l alpha ketoglutarate also increased the 5 minute survival of the organism in 0.2 mol/l citrate buffer containing 50 mmol/l urea to 36% (9-145%) compared with its survival in the same buffer but without preincubation with alpha ketoglutarate 0% (0-62%). CONCLUSION: The protection of H pylori from rapid destruction by the supply of compounds used in the intracellular metabolism of the ammonium shows that the urease mediated destruction of H pylori can be explained by intracellular depletion of alpha ketoglutarate as a result of over production of ammonium by uncontrolled urease activity. PMID- 8432896 TI - Evaluation of new streptococcal latex grouping kit. AB - AIMS: To evaluate a new streptococcal latex grouping kit (Shield Diagnostics Ltd) and compare it against an established latex agglutination method (Streptex; Wellcome Diagnostics). METHODS: Two hundred and forty seven strains of streptococci and enterococci were tested with each kit by one operator and according to the manufacturer's instructions. Strains failing to group or giving discordant results were identified to species level. RESULTS: Two discrepant grouping results were observed and 13 non-beta haemolytic streptococci failed to group with either product. The Shield kit successfully identified 232 isolates at 15 minutes of enzyme extraction incubation compared with 224 and 233 on short (15 minutes) and long (1 hour) incubations, respectively, for Streptex (p > 0.23 for both comparisons). On short incubation only, the Shield kit detected significantly more strains of Enterococcus faecium (p = 0.007). The reaction strengths were similar for both kits (p > 0.16). No cross-reactions were observed but the Streptex kit produced significantly fewer tests with visible granularity (p < 0.003). CONCLUSIONS: Although the Shield product appeared to detect group D antigen more readily, overall no important differences in performance were observed. Prospective users of the new method should first become familiar with its characteristics. PMID- 8432897 TI - Electron microscopic and immunohistochemical findings in a case of olfactory neuroblastoma. AB - A case of olfactory neuroblastoma is reported. Light microscopic examination showed various arrangements of poorly differentiated tumour cells forming either uniform sheets or convoluted cords of multiple cell layers orientated toward a richly vascular stroma. Electron microscopic examination showed the presence of abundant cytoplasmic filaments and processes, and dense core endocrine vesicles ranging from 100-160 nm in diameter in both the perinuclear region and tumour cell processes. Immunohistochemical staining was positive in most of the tumour cells for neuron specific enolase, and in a few cells for S-100 protein, vimentin, and serotonin, but staining for desmin and keratin produced no reaction. PMID- 8432898 TI - Mast cell numbers in melanocytic naevi and cutaneous neurofibromas. AB - This study aimed to determine the diagnostic utility of mast cell densities in distinguishing neurotised ("neural") melanocytic naevi from neurofibromas. Three groups of lesions were studied: neurofibromas, neural naevi, and naevi showing no neural change (control naevi). A Giemsa stain was used to demonstrate mast cells. The median mast cell density in the neurotised naevus group was significantly higher (p < 0.005) than that of both the neurofibroma and control naevus groups, but the distributions of the individual density counts overlapped considerably. The sensitivity and specificity of the mast cell density as a potential discriminator between neurotised naevi and neurofibromas, determined in relation to the optimal discrimination value obtained using Bayes' minimum cost decision rule, were low. It is concluded that mast cell density on its own is of little use as a classification tool but could be of value in the context of a multivariate decision rule. PMID- 8432899 TI - Xanthogranulomatous gastritis: association with xanthogranulomatous cholecystitis. AB - A case of xanthogranulomatous inflammation of the gastric wall is reported. The lesion was associated with adherent xanthogranulomatous cholecystitis and simulated, clinically, a malignant neoplasm. Histologically, foamy histiocytes, multi-nucleated giant cells, other inflammatory cells, fibrous reaction with spindle cells and cholesterol clefts were found. PMID- 8432901 TI - Origin of non-dialysable urinary glucoconjugates. AB - A Gel exclusion chromatographic method was used to determine the molecular weight distribution, and therefore, the origin, of non-dialysable urinary glucoconjugates in normal men. The results showed a mixture of glucoconjugates with molecular weight ranges of 1605 to 141,000. It is suggested that the high molecular weight forms originally constitute the glucoconjugates, and that they are probably post-glomerular in origin. These may be degraded in vivo by glucosylhydrolases to produce the low molecular weight forms. The activities of the urinary enzymes may be reduced in male type 1 diabetic patients, and this may be responsible for the reported increase in their excretion of non-dialysable urinary glucoconjugates. PMID- 8432900 TI - Florid vascular proliferation in repeated intussusception mimicking primary angiomatous lesion. AB - A case of recurrent intussusception in a 76 year old man associated with vascular proliferation is reported. The initial biopsy specimen showed that ulceration and inflammation were not features. The proliferation was so florid as to point to an angiomatous lesion. At this stage a diagnosis of intussusception was not considered. The clinical impression was that of a caecal mass associated with a filling defect visible on barium enema and a fleshy "suspicious" lesion on colonoscopy. This case illustrates the possibility of misinterpreting the importance of florid vascular proliferation in biopsy material where other features indicative of a reparative process are absent. PMID- 8432902 TI - Developmental expression of the prothoracicotropic hormone in the CNS of the tobacco hornworm Manduca sexta. AB - The prothoracicotropic hormone is an insect neuropeptide released into the hemolymph to signal molting and metamorphosis through its stimulation of steroidogenesis. The only known source of the prothoracicotropic hormone in the tobacco hornworm, Manduca sexta, has been a group of lateral cerebral neurosecretory cells, the L-NSC III. In this study, the developmental and spatial distribution of the prothoracicotropic hormone was examined throughout the life cycle of Manduca. In common with many vertebrates and invertebrates in which neuropeptides are located in several regions within the central nervous system (CNS), the prothoracicotropic hormone phenotype in Manduca is expressed by CNS neurons in addition to the L-NSC III. These neurons are located in the brain, frontal ganglion, and subesophageal ganglion. One cerebral neurosecretory cell group, the ventromedial neurons, expresses the prothoracicotropic hormone phenotype and the behavioral neurohormone, eclosion hormone. Whereas the L-NSC III and the ventromedial neurons express the peptide phenotype throughout the life cycle, the other neurons express the peptide only during the embryonic and larval stages. This precise spatial and temporal expression of the prothoracicotropic hormone by different groups of neurosecretory cells raises the possibility that in Manduca the peptide may, in addition to its known neuroendocrine function, play other physiological roles in different ways at different stages of the life cycle. PMID- 8432903 TI - Estrogen receptors in the avian brain: survey reveals general distribution and forebrain areas unique to songbirds. AB - Estrogens play an important role in the control and differentiation of species typical behavior and in endocrine homeostasis of birds, but the distribution and evolution of cells that contain estrogen receptors in the avian brain are poorly understood. This study therefore surveys 26 species in the avian orders Anseriformes (1 species), Galliformes (2), Columbiformes (3), Psittaciformes (1), Apodiformes (2), and Passeriformes (3 suboscines, 14 oscines). Indirect immunocytochemistry with the estrogen receptor (ER) antibody H222Spy revealed a general pattern of ER-antibody-immunoreactive cells (ER-IRC) in all 26 species, with ER-IRC in consistent, well-defined locations in the limbic forebrain, the midbrain striatum, the hippocampus, the hindbrain, and especially in the preoptic area and the tuberal hypothalamus. For some species, the microdistribution of ER IRC in some of these general areas differed, such as in the hippocampus and the anterior hypothalamus of suboscine species and in the preoptic area of the Japanese quail. Brains of oscine songbirds of both sexes, unlike brains of nonsongbirds, had ER-IRC in three specific structures of the nonlimbic forebrain: in the area surrounding the nucleus robustus archistriatalis; in the rostral forebrain; and, for all individuals, in the caudale neostriatum, including the nucleus hyperstriatalis ventrale, pars caudale (HVc). Among songbird families or subfamilies, adult males of the Estrildinae had much lower numbers of ER-IRC in HVc than did adult males of the Fringillidae, Paridae, Sturnidae, and Ploceinae. Differences occurred, too, among closely related species: the songbird canary (Serinus canaria) had an ER-IRC area in the rostral forebrain that was lacking in all other songbird species, including other cardueline finches. The cells with ER that are found only in the songbird forebrain but not in reptiles, nonpasserine birds, and nonoscine passerine birds very likely coevolved with steroid-dependent differentiation of vocal control areas. The songbird-specific expression of ER in the forebrain could be an example in which taxon-specific behavior is due to taxon specific neurochemical properties of the brain. PMID- 8432904 TI - Characterization of microglial reaction after middle cerebral artery occlusion in rat brain. AB - We have studied the microglial reaction that accompanies cortical infarction induced by middle cerebral artery occlusion (MCAO). Lectin histochemistry with the B4-isolectin from Griffonia simplicifolia as well as immunocytochemistry with a panel of monoclonal antibodies directed against major histocompatibility complex (MHC) and lymphocytic antigens were performed. Principal attention was focused on neocortical and thalamic regions, representative of primary and secondary ischemic damage, respectively. With the lectin procedure, activated microglial cells were abundant in the neocortex 24 hours after MCAO. In contrast, microglial activation in the thalamus was not apparent until day 2 after MCAO. On day 5, MHC class II antigen was expressed by reactive microglia in fiber tracts traversing the striatum, but was absent from activated microglia in the primary cortical infarction area. MHC class I and lymphocytic antigens were expressed differentially on microglia with class I antigens appearing early and lymphocytic antigens appearing late in the time course after focal ischemia. The findings are compatible with previous studies during global ischemia and confirm the early activation and the progressive nature of immunomolecule expression on activated microglia after an ischemic insult. In addition to neocortical and thalamic sites, our results showed an early microglial activation to be present also in forebrain regions outside of the middle cerebral artery (MCA) territory, such as the contralateral cortex and hippocampus. A unilateral microglial reaction was also detectable after long-term survival (> or = 4 weeks) in the pyramidal tracts, as well as in the corticospinal tracts at cervical but not lumbar spinal cord levels. Ischemia-induced neuronal damage, as evaluated by Nissl staining, was found only in cortical and thalamic regions. We conclude that the demonstration of reactive microglia indicates not only imminent ischemic neuronal damage within MCA territory but can also delineate extra-focal disturbances, possibly reflecting subtle and transitory changes in neuronal activity. PMID- 8432905 TI - Development of the dorsal root ganglion in a teleost, Oreochromis mossambicus (Peters). AB - The precursor crest cells of the spinal dorsal root ganglia (DRG) in the tilapia, Oreochromis mossambicus, were analysed by HNK-1 antibody staining, scanning electron microscopy, and DiI labeling techniques. The ontogeny of the DRG was followed in the embryos and young fry of the fish. Neural crest cells which contribute to the formation of the DRG were observed to commence their migration in the trunk region after 40 hours postfertilization. They do not penetrate the somites but travel through the space between the neural tube and the somite. Crest cells destined to become the DRG accumulate at the midsomitic region where the ventral root exits. At 50 to 80 hours postfertilization, they differentiate and become bipolar sensory cells. The DRG continues to grow and develop right through hatching at 115 hours. During the early larval stages, crest cells accumulate around the ventral root and the DRG eventually fuses with the motor root, giving rise to a situation in which the DRG contains not only the sensory cells but also motor fibres. The mixed nature of the DRG was confirmed by HRP retrograde labeling. We believe that this is the first report in describing the formation of the DRG in a teleost. PMID- 8432906 TI - Central projections of auditory nerve fibers of differing spontaneous rate, II: Posteroventral and dorsal cochlear nuclei. AB - Response properties of auditory nerve fibers (ANFs), including threshold sensitivity, vary systematically with spontaneous discharge rate (SR) (Liberman, M.C.: J. Acoust. Soc Amer. 63:442-455, 1978). Thus, an understanding of the mechanisms underlying signal transformation in the cochlear nucleus (CN) must include a description of any SR-based difference in ANF projections. This study is the second of a pair describing the CN projections of intracellularly labeled ANFs of known SR, the first of which summarized projection to the anteroventral CN (Liberman, M.C.: J. Comp. Neurol. 313:240-258, 1991). For each swelling from each labeled fiber, the position (within CN subdivisions), the size, and the type of cell contacted (if determinable) was noted: roughly one in four labeled swellings appeared in intimate contact with the soma or proximal dendrites of a CN cell. In all such cases, cell size and swelling size were measured. As reported for auteroventral cochlear nucleus, the ANF innervation of the small cell regions of posteroventral CN (PVCN) was almost exclusively by low- and medium-SR fibers. Other significant SR-based trends in ANF projections included 1) a tendency for high-SR fibers to contact larger cells in PVCN, 2) a meager projection of low- and medium-SR fibers to octopus cells, and 3) a tendency in the dorsal CN (DCN) for low-SR terminals to end closer to the fusiform cell layer than high-SR terminals. There were no significant SR-based difference in ANF swelling sizes in any subdivision. A consideration of the average cell sizes, ANF swelling sizes and estimated numbers of ANFs of different CF and SR converging on each CN cell help explain some of the differences in response transformation associated with different cell types in the CN. PMID- 8432907 TI - Two distinct phases characterize maturation of neurons in the nucleus of the tractus solitarius during early development: morphological and electrophysiological evidence. AB - We have used electrophysiology and light microscopy of intracellularly labeled neurons in the nucleus of the tractus solitarius (nTS) in brainstem slices of the newborn rat (P0 to P6) to examine the functional and morphological correlation of their development. Three-dimensional reconstruction of neurons injected intracellularly with biocytin, following electrophysiological recording, revealed a close correspondence between morphological immaturity (appearing as polarization of the dendritic tree) and the absence of a ramp-like voltage trajectory at the offset of hyperpolarizing current injections-IA negativity (8 of the 8 cells examined showed this correlation). These morphologically polarized IA negative neurons showed preferential dendritic sprouting in two diametrically opposite poles of the perikaryon. The orientation of the polarity differed according to the rostrocaudal location of the neuron. The appearance of a polarized dendritic tree during the first (immature) phase was transient and closely coincident with IA negativity. Following the development of adult-like electrophysiological characteristics, i.e., IA positivity, nucleus of the tractus solitarius neurons showed remarkably different morphological features (9 of 10 cells). These included a wide-spread branching of the dendritic tree in all directions, giving it a bushy appearance (cell body to dendrite ratio of 1:40). Numerous dendritic spines, growth cones on both dendrites and axons, and axon collateralization were present during both phases and indicate that nTS neurons during the two phases of early development demonstrate dynamic features of growth and maturation. The development of adult-like electrophysiological characteristics, i.e., IA positivity, progressively increased in the postnatal period. During the later part of the first postnatal week, twice as many neurons showed IA positivity in days P3 to P6 as compared with days P0 to P2. These results reveal the dynamic nature of neurons in the nTS during early development and illustrate the close link between morphology and functional characteristics in this region. We suggest that the establishment of adult-like morphology can be modified by appropriate environmental clues provided to nTS neurons during the initial (immature) phase of early postnatal development. PMID- 8432908 TI - Cholinergic innervation of the mediodorsal thalamic nucleus in the monkey: ultrastructural evidence supportive of functional diversity. AB - The ultrastructural organization of association nuclei in the primate thalamus is largely unexplored. In the present study we have combined electron microscopy with immunocytochemistry for the acetylcholine synthesizing enzyme choline acetyltransferase (ChAT) to assess the cholinergic synaptic organization of the mediodorsal (MD) nucleus in macaque monkeys. The cholinergic innervation of the MD nucleus showed striking regional variations with the greatest density of immunoreactive axons and varicosities found within the parvicellular division. Electron microscopic examination revealed that these ChAT immunoreactive (ChAT IR) axons were primarily small and unmyelinated. The majority of immunoreactive synaptic profiles were found within the extraglomerular neuropil (80.5%), with the remainder present in glomerular regions. Within the glomerular and extra glomerular neuropil ChAT-IR profiles made contact with both conventional, presumably relay cell dendrites (CD), as well as with synaptic vesicle containing dendrites (SVCD) of local circuit neurons. In the glomeruli the frequency of synapses was approximately equal for CDs and SVCDs while in the extraglomerular areas 75% of the synaptic contacts were with CDs. ChAT-IR synaptic profiles had a diversity of junctional complex morphologies. Within glomeruli they made symmetric synapses with CDs and predominantly asymmetric with SVCDs. The majority of extraglomerular contacts (60%) were classified as asymmetric and these as well as the smaller number of symmetric synapses contacted both CDs and SVCDs. In accord with results of physiological studies, these anatomical data indicate that cholinergic input to thalamic nuclei influences relay cell activity both directly and indirectly via local circuit neurons. PMID- 8432909 TI - A quantitative dendritic analysis of Wernicke's area in humans. I. Lifespan changes. AB - Age-related increases and decreases have been described in cortical dendritic neuropil. Here, we examine age-related changes in the basilar dendrites of supragranular pyramidal cells in human superior temporal gyrus (i.e., Wernicke's area) of left and right hemispheres. Tissue was obtained from 20 neurologically normal right-handers from 18-79 years: 10 males (Mage = 52.2 years; SDage = 17.4) and 10 females (Mage = 47.8; SDage = 20.5). In tissue prepared by a modified rapid Golgi technique, ten pyramidal cells were sampled from each hemisphere and evaluated according to the following parameters: total dendritic length, mean dendritic length, and dendritic segment count. Despite considerable interindividual variation, the data exhibited significant dendritic degeneration with aging. There was an age-related decrease in total dendritic length (r[20] = 0.44; P < 0.05) and especially in mean dendritic length (r[20] = -0.69; P < 0.001) with increasing age. Age-mean dendritic length correlations were negative for all segment orders and revealed a progressive decrease in segment length in more distal branches. The number of dendritic segments remained relatively stable across the age span sampled. The data also indicated that interhemispheric dendritic asymmetries decreased with age. Individuals under 50 years of age had significantly greater total dendritic length values in the left hemisphere. Interhemispheric dendritic differences were not significant in individuals over 50. PMID- 8432910 TI - A quantitative dendritic analysis of Wernicke's area in humans. II. Gender, hemispheric, and environmental factors. AB - This quantitative Golgi study extends our investigation of relationships between cortical dendrite systems in humans and higher cognitive functions. Here we examine the relationship between the basilar dendrites of supragranular pyramidal cells in Wernicke's area and selected intrinsic (i.e., gender and hemisphere) and extrinsic (i.e., education and personal history) variables. Tissue was obtained from 20 neurologically normal right-handers: 10 males (Mage = 52.2) and 10 females (Mage = 47.8). Several independent variables were investigated: GENDER (male, female), HEMISPHERE (left, right), and EDUCATION (less than high school, high school, and university). These were evaluated according to Total Dendritic Length, Mean Dendritic Length, and Dendritic Segment Count. A distinction was made between proximal (1st, 2nd, and 3rd order) and ontogenetically later developing distal (4th order and above) branches. There was significant interindividual variation in dendritic measurements, which roughly reflected individuals' personal backgrounds. Females exhibited slightly greater dendritic values and variability than males across the age range examined. On the whole, the left hemisphere maintained a slight advantage over the right hemisphere for all dendritic measures when all subjects were pooled, but these differences were not in a consistent direction across individuals. Education had a consistent and substantial effect such that dendritic measures increased as educational levels increased. Dendritic differences between independent variable levels were most clearly illustrated in the total dendritic length of 3rd and 4th order branches. Distal dendritic branches appeared to exhibit greater epigenetic flexibility than proximal dendrites. The present findings concur with environmental enrichment research results in animals and suggest that dendritic systems in humans function as a sensitive indicator of an individual's (a)vocational activities. PMID- 8432911 TI - Cutaneous markers of internal malignancy. II. Paraneoplastic dermatoses and environmental carcinogens. AB - A variety of cutaneous disorders may reflect the presence of an internal disease. The ability to recognize those that may indicate an underlying malignancy is of particular importance. In part I of this series malignant involvement of the skin, either direct or metastatic, and the genodermatoses with malignant potential were reviewed. In this portion, we describe the paraneoplastic dermatoses as well as the cutaneous effects of some environmental carcinogens associated with internal malignancy. In addition, several uncommon and controversial associations between benign dermatoses and internal malignant disease will be discussed. PMID- 8432912 TI - Clinical features of inflammatory dermatoses in human immunodeficiency virus type 1 disease and their correlation with Walter Reed stage. Military Medical Consortium for Applied Retroviral Research. AB - BACKGROUND: As part of a military study of the natural history of human immunodeficiency virus type 1 (HIV-1) disease, all patients entered in the study were examined for cutaneous changes associated with HIV-1 infection. OBJECTIVE: Our purpose was to characterize and record the types of inflammatory dermatoses in a large number of HIV-1-infected patients to determine whether there was a correlation with the stage of disease. METHODS: The clinical findings in each case were compared with the results of cultures and biopsy specimens and correlated with Walter Reed stage. RESULTS: Most of the inflammatory dermatoses were maculopapular eruptions often with prominent follicular involvement, and in some there was a lichenoid component. With increasing Walter Reed stage, many eruptions become papulosquamous, some with psoriasiform scale and some with a hypertrophic lichenoid appearance. CONCLUSION: Although most of the inflammatory eruptions were nonspecific clinically, most cases showed features resembling those in graft-versus-host disease. PMID- 8432913 TI - Histopathologic and immunohistochemical findings associated with inflammatory dermatoses in human immunodeficiency virus type 1 disease and their correlation with Walter Reed stage. Military Medical Consortium for Applied Retroviral Research. AB - BACKGROUND: Cutaneous lesions are common in patients with human immunodeficiency virus type 1 (HIV-1) infection. In many cases they are nonspecific inflammatory dermatoses. OBJECTIVE: Our goal was to determine whether features of these inflammatory dermatoses were characteristic of HIV-1 infection and whether the changes correlated with the stage of disease. METHODS: Biopsy specimens of inflammatory dermatoses from 176 HIV-1-infected patients in all Walter Reed stages were reviewed and the changes were compared with each WR stage. RESULTS: The changes found were nonspecific but were suggestive of features described in graft-versus-host disease and became more prominent in late-stage disease. CONCLUSION: A correlation was found between the changes and the stage of disease, and the findings add support to prior reports that at least some of the changes in HIV-1 infection may be autoimmune in origin. PMID- 8432914 TI - HLA antigens in anti-Ro(SS-A)-positive patients with recurrent annular erythema. AB - BACKGROUND: Recurrent annular erythema associated with the anti-Ro(SS-A) antibody response has recently been reported in Orientals. The association is assumed to represent a distinct clinical entity. OBJECTIVE: Our purpose was to extend knowledge on the immunogenetic spectrum of the disease. METHODS: Sixteen anti Ro(SS-A)-positive Japanese patients with recurrent annular erythema and Sjogren's syndrome were studied. The standard complement-dependent microcytotoxicity assay was used to type the HLA-A, -B, -C, -DR, and -DQ, as well as the HLA-DRw52 and DRw53 antigens. RESULTS: All 16 patients were positive for HLA-DRw52 antigens as compared with 52% of control subjects (p < 0.01 relative risk 14.8). No significant deviations were noted in the phenotype frequencies for HLA-A, -B, -C, and -DQ antigens. CONCLUSION: HLA-DRw52 is closely related to annular erythema in anti-Ro(SS-A)-positive Japanese patients with Sjogren's syndrome. PMID- 8432915 TI - Recombinant interferon gamma therapy for atopic dermatitis. AB - BACKGROUND: Atopic dermatitis is characterized by immunologic abnormalities including evidence for reduced interferon gamma production. Therapeutic options for treatment of atopic dermatitis are limited and unsatisfactory. Previous open trials have suggested efficacy for recombinant interferon-gamma (rIFN-gamma) in treatment of severe atopic dermatitis. We describe the results of treatment with rIFN-gamma, assessing clinical, immunologic, and laboratory safety parameters in 83 patients with moderate to severe atopic dermatitis. OBJECTIVE: Our purpose was to determine in a randomized, placebo-controlled, double-blind multicenter study the effects of recombinant human interferon gamma therapy in patients with atopic dermatitis. METHODS: Patients received 50 micrograms/m2 rIFN-gamma (n = 40) or placebo (n = 43) by daily subcutaneous injection for 12 weeks. Seventy-eight patients completed the treatment course; two patients receiving rIFN-gamma (one because of constitutional side effects) and three receiving placebo discontinued treatment before completion. Physician and patient overall response evaluations, clinical severity scores, body surface area involvement, and laboratory parameters were monitored throughout the trial. RESULTS: Patients in both treatment groups were similar except that the rIFN-gamma group was older and had a longer disease duration. Forty-five percent of rIFN-gamma-treated patients and 21% of placebo-treated patients achieved greater than 50% improvement in physicians' overall response evaluations (p = 0.016). As estimated by patients, responses also showed significant improvement in the rIFN-gamma group compared with the placebo group (53% vs 21%, p = 0.002). Significant reductions in erythema (p = 0.035) and in excoriations or erosions (p = 0.045) occurred in rIFN gamma-treated patients. Other atopic symptoms such as conjunctivitis (p < 0.002) were also reduced in the rIFN-gamma group. Occasional headaches, myalgias, or chills occurred in 30% to 60% of rIFN-gamma-treated patients but were effectively prevented by pretreatment acetaminophen and by dosing at bedtime. Grade II granulocytopenia occurred in five rIFN-gamma patients but normalized with continued treatment. Reduction to alternate-day dosing was necessary for six patients in the rIFN-gamma group and two in the placebo group. Seven had mild elevations of hepatic transaminase levels that did not affect therapy. The mean eosinophil count was significantly reduced (p = 0.003), whereas a nonsignificant increase in serum IgE levels occurred in the active treatment group. CONCLUSION: This study demonstrated that rIFN-gamma given by daily subcutaneous injection over a 12-week period was safe, well accepted, and effective in reducing inflammation, clinical symptoms, and eosinophilia in severe atopic dermatitis. PMID- 8432916 TI - Diagnostic significance of nailfold bleeding in scleroderma spectrum disorders. AB - BACKGROUND: The early detection of scleroderma spectrum disorders (SSD) is important. OBJECTIVE: Our purpose was to determine the prevalence of nailfold bleeding in SSD. METHODS: We examined patients for nailfold bleeding in the following three groups: (1) 81 patients with SSD including 50 patients with scleroderma, 10 with mixed connective tissue disease, and 21 with Raynaud's phenomenon having specific antinuclear antibody (ANA); (2) 99 patients with other connective tissue diseases or primary Raynaud's phenomenon; and (3) 200 patients with common skin diseases. RESULTS: The frequency of nailfold bleeding was significantly higher in SSD (75.3%) than in other connective tissue diseases (12.1%) and in controls (3.0%). The presence of nailfold bleeding in two or more fingers showed a 98.3% specificity for SSD. Among the patients with SSD, the incidence of nailfold bleeding in scleroderma, mixed connective tissue disease, and Raynaud's phenomenon with specific ANA was similar. Nailfold bleeding strongly correlated with the presence of anticentromere antibody. CONCLUSION: The presence of nailfold bleeding is useful for the early detection of SSD. PMID- 8432917 TI - Tanning facility compliance with state and federal regulations in North Carolina: a poor performance. AB - BACKGROUND: Little is known about the compliance of commercial tanning facilities with regulations governing their operation. We inspected some tanning parlors to assess the degree to which they follow federal and North Carolina state regulations. METHODS: An inspection of 32 tanning facilities was conducted between March and May 1991 as part of an ongoing effort to educate tanning parlor operators and proprietors about UV light safety. Compliance with each of 21 distinct state and federal requirements was recorded for each facility. RESULTS: Only 1 of 32 facilities was in complete compliance with both state and federal regulations. The number of infractions ranged from none to 21 (mean [+/- SD] 7.1 +/- 4.1). Nineteen percent of facilities had timers that were not within the required +/- 10% accuracy level. Twenty-two percent also had timers that did not meet Code of Federal Regulations standards. The estimated proportion of the total light output in the UVB spectrum ranged from 0.5% to 5.0% (mean 4.25% +/- 0.95%). CONCLUSIONS: These limited data suggest that many commercial tanning establishments are not uniformly compliant with regulations. Although we cannot extrapolate these findings to other states, we anticipate that facilities in states with less rigorous regulations than North Carolina have similar or inferior safety profiles. PMID- 8432918 TI - Quantitative and qualitative assessment of plasma von Willebrand factor in classic Kaposi's sarcoma. AB - BACKGROUND: von Willebrand factor (vWF) is synthesized almost exclusively by endothelial cells and is stored there as ultra-high-molecular-weight multimers. The vWF multimers that are detected in the plasma are smaller than those stored within the endothelium. In two previous studies, comprising small series of cases with classic Kaposi's sarcoma (KS), an endothelium-derived tumor, increased levels of plasma von Willebrand factor antigen (VWF:Ag, the antigenic structure) were reported, suggesting that vWF:Ag may be a marker of endothelium proliferation. OBJECTIVE: Our purpose was to investigate the quantitative as well as qualitative alterations of plasma vWF in a large series of patients with classic KS at various stages of the disease. METHODS: Levels of plasma vWF:Ag were studied in 38 patients with classic KS confined to the skin at various stages of the disease and compared with a control group. Thirty-three patients had active KS (i.e., with skin lesions) and five were in remission. In five patients with active KS multimeric analysis of plasma vWF was also performed. RESULTS: The levels of vWF:Ag were significantly higher among KS patients than in the control group (n = 29, p < 0.01). Levels of vWF:Ag were also significantly higher in patients with active disease as compared with those in remission (p < 0.05). No correlation was found between vWF:Ag levels and the extent of KS. Analysis of the multimeric pattern of plasma vWF showed enhanced staining of all bands, particularly the intermediate and high molecular weight forms, which resemble the endothelial forms as opposed to normal circulating vWF multimers. CONCLUSION: Quantitative as well as qualitative alterations in plasma vWF were found in patients with KS, which may reflect the destruction or activation of endothelial cells within the lesions. vWF:Ag may serve as a marker of disease activity in classic KS; however, it is not a good marker for the extent of the disease. PMID- 8432919 TI - Immunohistochemical and immunoelectron microscopic demonstration of chromogranin A in formalin-fixed tissue of Merkel cell carcinoma. AB - BACKGROUND: Chromogranin A (CGA) is the major protein of neurosecretory granules (NSG) of cells of the diffuse neuroendocrine system, and the amount of CGA corresponds to the number of NSGs. OBJECTIVE: Because formalin fixation may destroy NSGs, a study was performed to examine the presence of CGA in Merkel cell carcinoma (MCC) to determine whether CGA depends on the presence of intact NSGs. METHODS: Formalin-fixed, paraffin-embedded tissue of 15 MCCs was investigated by immunohistochemistry and immunoelectron microscopy for the presence of CGA and NSGs. RESULTS: CGA was demonstrated in 12 of 15 MCCs by immunochemistry and in 6 of 10 MCCs by immunoelectron microscopy although intact NSGs could not be discerned in all cases. CONCLUSION: CGA remains demonstrable even when no morphologically intact NSGs are present, which suggests that CGA is not exclusively responsible for the electron density of NSGs. PMID- 8432920 TI - Narrow-band UVB (311 nm) versus conventional broad-band UVB with and without dithranol in phototherapy for psoriasis. AB - BACKGROUND: A narrow-band UVB lamp (Philips TL 01) emitting a peak of approximately 311 nm was developed to improve the phototherapy for psoriasis. Only a few studies have been performed with promising results. OBJECTIVE: The therapeutic efficacy of the Philips TL 01 lamp in a new 100 W version was compared with conventional broad-band lamps (Sylvania UV 6) in a controlled trial. METHODS: Twenty-three patients with psoriasis were treated with half-body exposures from the different UVB sources. The rate of clearing was monitored by estimation of the Psoriasis Area and Severity Index. All patients used emollients; excessive scaling was removed with salicylic acid in yellow petrolatum. In 13 patients dithranol in a modified Ingram regimen was added. In most cases the study was discontinued once a difference between the two sides was evident. RESULTS: In 20 of 23 cases the TL 01 lamp proved to be significantly more effective than the conventional source. Application of dithranol provided a substantial additional therapeutic effect. With the high-intensity TL 01/100W bulbs, exposure times were comparable to broad-band UVB phototherapy. CONCLUSION: The therapeutic efficacy of Philips TL 01/100W and its practicability for psoriasis phototherapy have been demonstrated. PMID- 8432921 TI - A novel therapy for atopic dermatitis with allergen-antibody complexes: a double blind, placebo-controlled study. AB - BACKGROUND: Exposure to airborne allergens exacerbates symptoms of atopic dermatitis (AD) in hypersensitive patients. OBJECTIVE: Our purpose was to determine whether the administration of allergen-antibody complexes would improve the symptoms of AD. METHODS: Twenty-four adults with AD and hypersensitivity to Dermatophagoides pteronyssinus (Dpt) were treated in a double-blind, placebo controlled trial by intradermal injections of complexes containing autologous specific antibodies and Dpt allergens. After 4 months, placebo-treated patients started receiving active treatment. All patients were treated for a full year. Clinical status and Dpt-specific IgG and IgE antibody levels were monitored. RESULTS: Symptoms of AD subsided within a few weeks after starting therapy, with significant reduction after 4 months in treated patients only. After 1 year, 82% of the patients exhibited a mean improvement of 83%, associated with reduction of Dpt-specific IgG antibodies. CONCLUSION: The treatment of Dpt-sensitive patients with AD by injections of allergen-antibody complexes is safe and effective in a majority of patients. PMID- 8432922 TI - Chronic actinic dermatitis. AB - Chronic actinic dermatitis (CAD) is one of the most frequently encountered photodermatoses in patients older than 50 years of age. It is characterized by persistent redness of the face and other exposed areas. CAD can become so severe that even nonexposed parts of the body develop eczematous lesions and the disease persists during winter. The diagnosis must be confirmed by phototests that show a broad action spectrum with low threshold doses. CAD must be differentiated from photocontact allergy and airborne dermatitis. The histopathologic features in the early stages are comparable to contact dermatitis, whereas in the later stages they may be those of pseudolymphoma. The most popular treatments are azathioprine and PUVA. PMID- 8432923 TI - Hyperpigmentation and secondary hemochromatosis: a novel treatment with extracorporeal chelation. PMID- 8432924 TI - Cutaneous myiasis. PMID- 8432925 TI - Eczema herpeticum in association with familial benign chronic pemphigus. PMID- 8432926 TI - Persistent allergic contact dermatitis from squaric acid dibutyl ester. PMID- 8432927 TI - Furuncular cutaneous myiasis caused by Cuterebra larva. PMID- 8432928 TI - Pseudomelanoma after dermabrasion. PMID- 8432929 TI - Acute pustular eruption: an unusual clinical feature of disseminated mycobacterial infection in patients with acquired immunodeficiency syndrome. PMID- 8432930 TI - Giant lipoma: case report and review of the literature. PMID- 8432931 TI - A caution in the evaluation of scar revision. PMID- 8432932 TI - Thalidomide: treatment of choice for aphthous ulcers in patients seropositive for human immunodeficiency virus. PMID- 8432933 TI - Posttraumatic nevus comedonicus. PMID- 8432934 TI - Dermatopathia pigmentosa reticularis. PMID- 8432935 TI - Pool palms. PMID- 8432936 TI - Prognostic factors for local recurrence, metastases, and survival rates in squamous cell carcinoma of the skin, ear, and lip. PMID- 8432937 TI - Pseudoxanthoma elasticum-like papillary dermal elastolysis. PMID- 8432938 TI - Tretinoin emollient cream. PMID- 8432939 TI - Adolescent turmoil. PMID- 8432940 TI - Oral cleanliness of dentally anxious schoolchildren and their need for periodontal treatment. AB - The aim of this study was to examine the relationship between self-reported dental anxiety and the oral cleanliness and periodontal treatment need in Scottish secondary schoolchildren. One thousand one hundred and three children participated in the study, mean age 14 years (sd 0.35 years), and the prevalence of high dental anxiety was 7.1 percent (95 percent CI = 5.6 percent, 8.6 percent). In examining the hypothesis that anxious children are more likely to have 'cleaner' mouths in an attempt to avoid future dental treatment, it was found that children with high dental anxiety or general fear had similar overall oral cleanliness (mean debris score and CPITN) to their contemporaries. However, dentally anxious children have less contact with the dental team; that is, they were more likely to defer or cancel dental appointments. Gender and social class were more significant variables in the presence and absence of disease with regard to CPITN than were either dental or general anxiety. It is concluded that no difference could be detected regarding the periodontal treatment needs between those children who have or have not a self reported high dental anxiety. In addition the periodontal needs of the majority of this age-group (64 percent) and those with high dental anxiety (74 percent) can be treated with simple non invasive dental procedures, which can be carried outside the context of a dental surgery. PMID- 8432941 TI - A child's sleeping habit as a cause of nursing caries. AB - A survey was conducted to determine the relationship between infant bottle drinking patterns and "nursing caries". The sleeping habits of the child, the contents of the bottle, the age at which the child was weaned from the bottle, and the age at which toothbrushing commenced were evaluated. Information was obtained through a parental questionnaire and a clinical examination. The results indicate that children who fell asleep while feeding from the bottle had significantly more cases of "nursing caries" than did children who discarded the bottle before falling asleep. Children who discarded the bottle before falling asleep, however, had significantly more cases of "nursing caries" than did children who were not given the bottle at all at bedtime. All other factors were not significant in increasing or decreasing the incidence of "nursing caries". PMID- 8432942 TI - Local treatment of minor aphthous ulceration in children. AB - Pain is commonly associated with minor aphthous ulceration in children. It results mostly from secondary infection and lasts from eighteen hours to three days. The use of a cyanoacrylate adhesive provides a symptomatic relief within minutes and shortens the healing time. PMID- 8432943 TI - Impaction and malformation of a maxillary central incisor: sequelae of trauma. PMID- 8432944 TI - Parental education leads to preventive dental treatment for patients under the age of four. AB - Records from a pediatric dentist's practice, for selected periods of time over a twenty-three-year span (1966-1988), were reviewed to determine the number of patients under four years of age seen for initial dental visits and the reason for the first visit. Reasons given by parents seeking dental care for their children were categorized thus: preventive services, oral injuries, dental caries, and "other" conditions. A parental education system that stressed the benefits of a home-care program and early dental visits resulted in a 36.7 percent increase in children under the age of four seen for preventive services. Special note was taken of the influence of this program on the parents' decision to seek early preventive care for younger siblings of patients already in the practice. PMID- 8432945 TI - Problems your pediatric patients may face. AB - Children are more that "just" pediatric dental patients. They may be the product of single parent families, families in economic difficulties, families that have experienced divorce and alcoholism. The children may have been subjected to neglect and/or abuse or may have required the services of mental health programs. A review is provided of the magnitude of these problems, which can and do affect the patients and the dental services that are provided. PMID- 8432946 TI - Trends in the perceived need for dental care for children: 1982-1990. AB - A review is provided of the national surveys of parents and guardians on the dental status and associated difficulties of their children. Although fewer in number, complaints of acute dental problems in children continue to be made. PMID- 8432947 TI - The composite resin restoration: a literature review. Part I. Proper cavity preparation and placement techniques. AB - Interest in nonalloy restorations have increased the usage of composite resins for Class II posterior lesions. Modifications of G.V. Black's original cavity design are discussed, to familiarize the practitioner with successful techniques that have increased the longevity of these restorations. The usage of bonding agents, and placement of the filled resin materials are also described. PMID- 8432948 TI - The composite resin restoration: a literature review. Part II. Comparisons between composite and alloy restorations. AB - Composite resin restorations have been advocated as a posterior restoration for Class II lesions, due to their esthetic quality and lack of mercury content. This report investigates early studies that compared amalgam and composite restorations, and cites their advantages and disadvantages. The various methods previous investigators implemented to assess the longevity of the restorations are also described. PMID- 8432949 TI - The composite resin restoration: a literature review, Part III. What the future holds. AB - This article discusses the evolution of composite resins as a posterior restoration and describes recent advances in both unfilled and filled resin materials. The future of today's composite material as an amalgam alternative is also described. PMID- 8432950 TI - Behavior management of a patient with Mobius syndrome: report of case. AB - A twelve-year old Mobius syndrome patient was successfully examined as an outpatient, using patience, tactile desensitization, and cooperative interaction. Restoration of carious teeth was accomplished, using general anesthesia. Behavioral intervention was successful, thus avoiding an unnecessary hospitalization for examination only. PMID- 8432951 TI - Enamel pearls in the primary dentition: report of two cases. AB - Two cases of enamel pearls present in the furcation area of primary mandibular second molars are reported. Clinical and histologic examination revealed that the pearls were composite enamel pearls. Complications arising from this uncommon entity may include delayed exfoliation of the primary tooth and/or deviation of the succedaneous tooth. Radiographic interpretation and detection of the enamel pearl may be complicated by the superimposition of the developing permanent tooth, and their incidence may be higher than reported. PMID- 8432952 TI - Neurofibroma of the gingiva in a child: report of case. AB - A rare case of neurofibroma in a two-year-old boy is reported, with details of light microscopy and immunohistochemistry. Microscopically, the tumor was composed of large spindle cells and small round cells. Immunohistochemically, moderative positivity for S-100, S-100 alpha and NSE was seen in the large spindle cells, but only weak positivity was evident in the small round cells. The large spindle cells were thought to be more differentiated than the small ones, because S-100 beta, a marker of well-differentiated nerve tumors, was identified only in the spindle cells. The large spindle cells may be derived from Schwann cells, and the small round cells from the perineurium cells. The literature on neurofibroma in children was reviewed and discussed. PMID- 8432953 TI - Vapor heat treatment for zucchini infested with Bactrocera cucumis (Diptera: Tephritidae). AB - Zucchini, Cucurbita pepo L., infested with 22-h-old eggs of Bactrocera cucumis (French) were completely disinfested using a vapor heat treatment of 45 degrees C with > 94% RH for 30 min. An estimated total of 178,219 eggs (22 h old) was treated without survivors, thus achieving probit 9 mortality. Twenty-two-h-old eggs were significantly more tolerant of heat than first, second, or third instars. All treatments were done in a Sanshu model EHK-1000B vapor heat treatment system. PMID- 8432954 TI - Therapist individuality in the diagnosis and treatment of depression. AB - The influence of physician variables on the diagnosis and treatment of depression was analysed by presenting a trained pseudo-patient to four physicians each with different professional backgrounds. Although all physicians had earlier given their informed consent to the study design, they thought that they were treating a real patient during regular practice hours. All physicians assessed the acute psychopathology almost completely except for suicidal thoughts. Despite similar information about the case, four different diagnoses/pathogenetic concepts and four different treatments were chosen. Medical decision processes and their results can be related to the professional background and personal attitudes of physicians. PMID- 8432955 TI - Concordance between clinical and self-report depression scales during the acute phase and after treatment. AB - The concordance between self-report and clinical rating scales of depression increases during progress from the acute depressive episode to recovery or improvement of symptoms. We investigated this convergence in a group of 52 outpatients with DSM-III major depression disorders using three widely employed depression scales and their parallel formats (i.e., alternative modes of administering the scales). The six instruments were applied at admission and after 12 and 24 weeks' treatment. The results indicate that the increase in the global concordance between scales may be a statistical effect deriving from broadening of the range of scores. PMID- 8432956 TI - Outpatient utilization of antidepressants: a prescription database analysis. AB - A prescription database analysis was conducted to describe the users of antidepressants outside hospitals in the Odense area (207,000 inhabitants) during one year. In total, 1.62% (N = 3360) of the population used antidepressants. Women and users aged over 70 years constituted a disproportionately large part. Seventy-five percent of the patients used tricyclic antidepressants. The estimated daily doses for the tricyclic antidepressants were generally low, the third quartile being less than 100 mg daily. The low doses may be due to antidepressants being used on other indications than depression or that a considerable number of the patients are not given a sufficient dose. PMID- 8432957 TI - Effects of tricyclic antidepressant treatment on tyramine-O-sulfate excretion in depressed patients. AB - The urinary excretion of tyramine-O-sulfate following an oral load of tyramine (Tyramine Challenge Test, 'TCT') was measured in a group of fourteen inpatients with unipolar and bipolar major depressive episode. TCT was done both during a pretreatment baseline period and following four weeks of treatment with tricyclic antidepressants. The change in TCT values after treatment correlated with improvement in depression. The previously described ability of TCT to discriminate between endogenous and nonendogenous depressed patients was confirmed at baseline. However, following tricyclic antidepressant treatment, TCT values were not significantly different between endogenous and nonendogenous patients. PMID- 8432958 TI - Features associated with suicide attempts in depression: a partial replication. AB - Clinical and symptomatic features were examined in relation to suicide attempts in a heterogenous group of depressed patients. Depressed patients who had attempted suicide had had their first episode of affective disorder at a significantly earlier age, had had significantly more episodes of affective disorder, and more of them had bipolar disorder. However, there was only one significant difference for baseline symptoms scores on four affective symptom rating scales. A family history of suicide was associated with a history of a violent suicide attempt. PMID- 8432959 TI - A comparison of sleep EEGs in patients with primary major depression and major depression secondary to alcoholism. AB - Polygraphic sleep recordings were compared between patients with primary major depression (MDD), patients with primary alcoholism and secondary MDD, and normals. Patients differed significantly from normals on the following measures: both patient groups showed short REM latency, and REM latency corrected, along with prolonged sleep latency. Secondary depressives differed from controls on several other measures: sleep onset time, total sleep time, delta sleep, REM percent, stage one sleep, stage three sleep, non-REM sleep, stage three and delta sleep in the first non-REM period. Prior research has shown a decrease in non-REM sleep and total sleep time in alcoholic patients who are not currently depressed, and short REM latency in patients with MDD. Thus, our findings suggest an additive effect of two disorders known to affect sleep: alcoholism and depression. PMID- 8432960 TI - Spouse concordance for depressive disorders in a community sample. AB - This article describes an analysis of spouse concordance for major depression and for other depressive experiences. Respondents to a community survey of married men and women (N = 586 couples) completed a modified version of the Diagnostic Interview Schedule from which diagnoses of major depression and dysthymia were derived. Subclinical depressive episodes were also identified. A cross-tabulation of husbands' and wives' diagnoses revealed weak concordance for lifetime prevalence of major depression. In contrast, concordance for the experience of depressive episodes, regardless of associated symptomatology, is statistically significant. Contrary to earlier suggestions, concordance does not increase over the length of the marriage, nor is it stronger among divorced couples. PMID- 8432961 TI - Alterations in brain phosphorous metabolism in bipolar disorder detected by in vivo 31P and 7Li magnetic resonance spectroscopy. AB - Phosphorus-31 magnetic resonance spectroscopy (MRS), able to detect membrane metabolism and intracellular pH as well as energy metabolism in vivo, was applied to 17 bipolar patients in the manic state and the euthymic state. In nine of these patients, brain lithium concentration was simultaneously determined by means of lithium-7 MRS in order to clarify the effect of treatment with lithium on brain phosphorous metabolism. Both phosphomonoester (PME) peak area and intracellular pH were found to be higher in the manic state than in the euthymic state. These values in the euthymic state were lower than those in normal controls whose ages and sexes were matched with the patients. However, PME and intracellular pH did not correlate to brain lithium concentration. These findings coincide with a hypothesis that patients with bipolar disorder may have membrane abnormality in their euthymic state and state-dependent alteration of catecholaminergic activity may be a secondary phenomenon. PMID- 8432962 TI - Detection of Borna disease virus-reactive antibodies from patients with affective disorders by western immunoblot technique. AB - Borna disease (BD) virus is a partially characterized neurotropic agent with a predilection for neurons and astrocytes in the limbic system and cerebrum of infected hosts. Although it usually causes a fatal encephalitis, some laboratory animals which have been experimentally inoculated can develop a persistent non fatal infection characterized by a neuro-behavioral syndrome akin to human manic depression. Using immunofluorescent techniques, we previously observed BD virus specific antibodies in the sera of 4.5% of affectively ill patients, with the highest titers present in bipolar patients. More recently, we have developed a sensitive Western blot assay for the detection of anti-BD virus antibodies to a 38/40 kDa and 24 kDa protein in human serum. In the present study, we screened 138 affectively ill patients and 117 healthy controls and observed a significantly great proportion of patients with antibodies to the 38/40 kDa protein (P < 0.0001), the 24 kDa protein (P < 0.05) and both the 38/40 kDa and 24 kDa proteins (P < 0.025). These data extend prior reports on the presence of BD virus-specific antibodies in psychiatric patients, and suggest that a BD virus like agent may be associated with affective illness in humans. PMID- 8432963 TI - Greek philosophy, medical ethics, and the influenza vaccine. PMID- 8432964 TI - Attitude of healthcare personnel regarding influenza immunization. AB - OBJECTIVES: To survey the attitudes of healthcare personnel regarding influenza immunization. DESIGN: A questionnaire was given to all hospital employees. SETTING: A 650-bed community teaching hospital. INTERVENTION: Employees were offered an in-service regarding influenza immunization in October 1991. Influenza immunization was given free of charge by Employee Health Services from October to December 1991. One thousand fifty-six employees (30.2%) received influenza vaccines. Survey forms were distributed with paychecks to all employees during the second half of January 1992. Completed survey forms were returned during the next 2 weeks. RESULTS: One thousand two hundred three of the 3501 (34.3%) questionnaires were returned. Some of the survey forms were not completely filled out. A total of 28.1% of male employees (202/717) and 35.4% of female employees (987/2783) (p < .01) responded. Mean years employed were 11.35 +/- 7.57 for respondents and 9.30 +/- 7.39 for all employees (p < .001). Four hundred sixty one respondents (38.4%) received the influenza vaccine and 734 (61.4%) did not. Among the respondents, employees who were older or working full time were more likely to receive the vaccine. Proportionally, more respondents who received the vaccine attended the in-service, although only 8.7% of those immunized attributed their receiving influenza vaccine to the in-service. More physician respondents were vaccinated. The respondents who received influenza vaccine were more likely to have received the vaccine during the past 2 years (p < .001). The major reasons given for not receiving the vaccine were "bad side effects" and "do not like shots." The major side effect of influenza immunization was a "sore arm." Multivariate analysis suggested that the in-service was not associated with obtaining the vaccine. CONCLUSIONS: The in-service regarding influenza immunization seemed to have a negligible influence. Most employees who received the vaccine had previous influenza immunization. There were no major side effects of influenza immunization. "Bad side effects" and "do not like shots" were major reasons given for not receiving influenza vaccine. PMID- 8432966 TI - Inactivation of Clostridium difficile spores by disinfectants. AB - OBJECTIVE: The current study was designed to evaluate the activity of glutaraldehyde-based disinfectants against Clostridium difficile using the Association of Official Analytical Chemists' (AOAC) sporicidal test. This study was undertaken because gastrointestinal endoscopes that may be contaminated with C difficile spores are most commonly disinfected between patients using glutaraldehyde-based disinfectants. DESIGN: Using the AOAC test, the following disinfectants were tested: 2% alkaline glutaraldehyde, 2% acid glutaraldehyde, a 1:16 dilution of a 2% glutaraldehyde-7.05% phenol-1.20% sodium phenate, and a 1:20 dilution of a 10% glutaraldehyde-0.5% phenylphenol-0.1% amylphenol. RESULTS: Test results of the four disinfectants against C difficile spores at exposure times of 10, 20, and 60 minutes were as follows (number of positive penicylinders per 30 replicates): 0, 0, and 0 for 2% alkaline glutaraldehyde; 6, 3, and 0 for 2% acid glutaraldehyde; 30, 29, and 30 for a 1:16 dilution of glutaraldehyde 7.05% phenol-1.20% sodium phenate; and 30, 30, and 30 for a 1:20 dilution of glutaraldehyde-0.5% phenylphenol-0.1% amylphenol. CONCLUSIONS: C difficile spores are more susceptible to inactivation by glutaraldehyde-based disinfectants than the spore-forming organisms recommended in the AOAC sporicidal test (i.e., Bacillus subtilis and Clostridium sporogenes). Diluting glutaraldehyde-based disinfectants below 2% led to the inability to inactivate spores of C difficile using exposure times commonly employed to disinfect semicritical items such as gastrointestinal endoscopes. PMID- 8432965 TI - Electronic surveillance of antibiotic exposure and coded discharge diagnoses as indicators of postoperative infection and other quality assurance measures. AB - OBJECTIVES: To assess postoperative exposure to parenteral antibiotics and coded discharge diagnoses of infection as markers of nosocomial infection, postoperative morbidity, and potentially inappropriate antibiotic use after cesarean section. DESIGN: Retrospective cohort study to compare automated markers with the criterion of record review. SETTING: Tertiary care hospital. PATIENTS: Women admitted to a large teaching hospital after April 15, 1987, and discharged before October 1, 1989, who underwent a nonrepeat, nonelective cesarean section and had received prophylaxis with a cephalosporin. METHODS: Antibiotic exposure and discharge diagnosis codes were obtained from a large electronic hospital data base. A sample of charts was reviewed to determine the presence of infection, other postoperative complications, and postoperative antibiotic exposure. RESULTS: A total of 2,197 women who had undergone a nonrepeat nonelective cesarean section were included in the study cohort. These women were assigned to 6 subgroups based on postoperative antibiotic exposure status and discharge codes suggesting endometritis, other postoperative infection, or no infection. Review of 457 records indicated that the overall infection rate was 9%. Eight percent of all the patients had a coded diagnosis for infection, and 16% received some parenteral antibiotics after the first postoperative day. Exposure to at least 2 days of parenteral postoperative antibiotics was the best marker by which to discriminate between infected and uninfected patients, with a sensitivity of 81%, a specificity of 95%, and a positive predictive value of 61% for detecting infection. The corresponding figures for coded diagnoses for infection had rates of 65%, 97%, and 74%, respectively. The combination of discharge codes and exposure to parenteral postoperative antibiotics resulted in a more accurate but less sensitive marker for nosocomial infections, with a positive predictive value of 94% and a sensitivity of 59%. The groups with discordant parenteral postoperative antibiotics exposure and discharge codes for infection were enriched for errors in coding, noninfectious morbidity, and unexplained antibiotic use. Less than 1% of the entire cohort had > or = to 2 days of parenteral postoperative antibiotics without any reason apparent in the medical record. CONCLUSIONS: Parenteral postoperative antibiotic exposure determined from automated pharmacy records correlated with the results of the more labor intensive manual review of medical records for the identification of nosocomial infection. In addition, information on antibiotic exposure combined with coded discharge diagnoses provided a rapid screen to identify subgroups of patients with higher rates of infectious and noninfectious morbidity, unexplained antibiotic use, and errors in discharge coding. Information derived from electronic data bases created for administrative purposes may be useful as a marker for infectious complications, inappropriate antibiotic prescribing, and other issues related to total quality hospital monitoring. PMID- 8432967 TI - Infection control in long-term care facilities: the hospital-based practitioner's role. PMID- 8432968 TI - Utility of epidemiologic training in long-term care settings. PMID- 8432969 TI - Dustbowls, disease, and the new deal: The Farm Security Administration migrant health programs, 1935-1947. PMID- 8432970 TI - Justin's madness: weak-mindedness or organic psychosis? PMID- 8432971 TI - The origins of the term "extrapyramidal" within the context of late nineteenth- and early twentieth-century neurology, neurophysiology and neuropathology. PMID- 8432972 TI - The history of the disease called lupus. PMID- 8432973 TI - A novel cytokine-responsive cell surface glycoprotein defines a subset of medullary thymic epithelium in situ. AB - A hamster mAb (10.1.1), raised against long term cultures of uncloned thymic stromal cells, selectively labeled a subpopulation of medullary stromal cells in situ. By ultrastructural and phenotypic criteria, the stromal cells labeled by this mAb were judged to be epithelial. Although some of the 10.1.1+ epithelial cells were reticular, others were globular and some were associated with structures resembling Hassal's bodies. Ultrastructural immunohistochemistry suggested that 10.1.1 labeling of some of the epithelial cells was preferentially associated at areas of epithelial cell contact with adjacent thymocytes. Reactivity of thymic stromal cells with this antibody was developmentally regulated. A few scattered 10.1.1+ cells were observed at day 14 of gestation, and there were progressive increases in both the extent and intensity of 10.1.1 labeling evident through birth. One thymic stromal cell line, Z210.1, exhibited low levels of constitutive reactivity with this antibody. Exposure to IL-1 resulted in enhanced 10.1.1 reactivity of this cell line, with little, if any, additional response to TNF-alpha or IFN-gamma. Under the same conditions, ICAM-1 expression by this cell line was elevated in response to IL-1, TNF-alpha, or INF gamma. Immunoprecipitation of detergent lysates prepared from Z210.1.7 cells exposed to IL-1 24 h before cell surface iodination identified a cell surface protein with a molecular mass of about 92 kDa under nonreducing conditions and about 95 kDa under reducing conditions. Digestion of 10.1.1 immunoprecipitates with N-glyconase resulted in a small (5 kDa) reduction in molecular mass. The molecule recognized by the 10.1.1 mAb was distinct from ICAM-1, which possessed a molecular mass of 100 kDa (nonreduced) and 110 kDa (reduced), and also displayed a smaller N-glyconase-resistant molecular mass (65 to 85 kDa). PMID- 8432974 TI - Antigen-independent processes in antigen-specific immunity. A role for alpha 4 integrin. AB - It has been proposed that the migration of immune T cells out of blood vessels through connective tissue to the site of antigenic challenge is facilitated by the interaction of VLA integrins on lymphocytes with endothelial cell adhesion molecules and matrix proteins. Indeed, we have recently demonstrated that peptides derived from sequences in fibronectin abrogate the T cell-mediated contact hypersensitivity (CHS) reactions in vivo. These peptides blocked the interaction of the integrins VLA-4 and VLA-5 with fibronectin (FN), and our results suggested that by preventing the interaction of T cell integrins with FN, we successfully prevented the migration of T cells to sites of antigenic challenge. To further explore the role of integrins in T cell migration, we have used an antibody (R1-2) specific for the alpha-chain of alpha 4 integrins. Our data show that this antibody stains more than 90% of CD3+ T cells, and this percentage does not change after the mice have been immunized with a contact sensitizer. We also show that this antibody blocks the interaction of cells with immobilized FN and vascular cell adhesion molecule-1 on activated endothelial cells. Although R1-2 identifies alpha 4 integrin on a large number of T cells, it does not discriminate between activated and resting forms of this integrin, because very few T cells from immune or nonimmune mice actually bind FN or activated endothelium. In vivo, antibody R1-2 effectively blocks Ag-specific CHS, but has little effect on the non-Ag-specific cells that localize to the site of antigenic challenge. The population of cells that adoptively transfer CHS exits with the population of cells that bind to FN or to activated endothelial cells. Our data demonstrate that a small number of Ag-specific T cells use alpha 4 integrin to enter sites of inflammation and mediate effector immune responses. Ag independent accumulation of T cells near sites of inflammation does not appear to be mediated by alpha 4 integrin. PMID- 8432975 TI - Inhibition of phorbol ester-induced T cell proliferation by bryostatin is associated with rapid degradation of protein kinase C. AB - The bryostatins (Bryo) represent a group of immunomodulators that counteract the tumor-promoting effects of PMA. In contrast to the mitogenic effect of PMA on human peripheral blood T lymphocytes, Bryo was nonmitogenic and, furthermore, it inhibited PMA-induced T cell proliferation in a dose-dependent manner when added up to 2 days after PMA. Because both Bryo and PMA bind to, and activate, protein kinase C (PKC), we compared their effects on PKC expression and activity in human PBL or leukemic T cells (Jurkat). After treatment for 5 to 60 min, both Bryo and PMA were found to: a) activate PKC in vitro with similar dose-response curves; b) induce a nearly complete cytosol-to-membrane translocation of enzymatically active, Ca(2+)-dependent PKC and of distinct immunoreactive PKC isoforms in intact PBL; and c) stimulate similar patterns of protein phosphorylation. After a longer, 20-h treatment with PMA (20 nM), a considerable portion of PKC was still membrane-associated, and the total amount of immunoreactive PKC was not reduced considerably. In contrast, Bryo induced a marked loss of cellular immunoreactive PKC, including PKC-alpha and -beta. These results were paralleled by measurements of total cytosol- or membrane-associated PKC enzymatic activity. Thus, substantial PKC activity was associated with the particulate fraction of PMA-, but not Bryo-stimulated PBL. Furthermore, inhibition of PMA-induced T cell proliferation by Bryo also correlated with a reduction in the amount of cytosolic and membrane-bound immunoreactive PKC and enzymatic activity, demonstrating the dominance of Bryo over PMA. We propose that Bryo inhibits PMA-induced T cell proliferation by causing rapid degradation of PKC, reflecting a requirement of persistent PKC stimulation (lasting approximately 48 h) for the activation of human T cells and progression through the cell cycle. PMID- 8432976 TI - IL-1 and tumor necrosis factor-alpha each up-regulate both the expression of IFN gamma receptors and enhance IFN-gamma-induced HLA-DR expression on human monocytes and a human monocytic cell line (THP-1). AB - Stimulation of human blood monocytes (adherent mononuclear cells) and the monocytic cell line, THP-1, by IL-1 or TNF-alpha leads to the up-regulation of IFN-gamma receptors. Scatchard analysis using 125I-IFN-gamma revealed a twofold increase in the number of IFN-gamma receptors on THP-1 cells without an alteration in the affinity of the receptor. The potential functional significance of this induction of IFN-gamma receptors on monocytes and THP-1 cells was investigated by examining the effect of IFN-gamma on MHC class II Ag expression by these cells. Both IL-1 and TNF-alpha enhanced the IFN-gamma-induced HLA-DR expression (> twofold) and this effect was inhibited by antibody to IFN-gamma. In the case of human monocytes, IL-1 or TNF-alpha, each by themselves also increased HLA-DR expression, which was also abrogated by antibody to IFN-gamma. The data suggest that the immunopotentiating effects of IL-1 and TNF-alpha are mediated in part by enhancing IFN-gamma receptor expression on monocytes and macrophages. This presumably would increase the capacity of IFN-gamma to activate macrophages, enabling them to express HLA-DR and present Ag more effectively. PMID- 8432977 TI - B lymphocyte development and activation independent of MHC class II expression. AB - A murine model of MHC class II deficiency created by targeted gene disruption was used to investigate whether class II expression influences B cell maturation and function. There appeared to be fewer total B cell precursors, a higher proportion of which were in a very early stage of maturation, in class II-deficient vs control bone marrow; however, the differences did not reach statistical significance. Mature B cells were unaffected; IgM, IgD, B220, and CD5 surface expression were similar in class II-deficient and control animals. Serum Ig determinations revealed that the class II-deficient animals had elevated IgM but decreased IgG1 (and, variably, IgE) compared to control. The antibody response against thymic-independent Ag was intact in class II-animals, as was the in vitro response of small resting B cells from class II deficient animals to stimulation with polyclonal B cell activators. Preactivated T cells were able to induce differentiation and proliferation of class II-deficient, small resting B cells. Together, these data indicate that B cell development, T cell-independent, and T cell-dependent B-cell activation, can occur independently of class II MHC expression. PMID- 8432978 TI - An evaluation of mechanisms by which tolerance to organ-specific antigens is lost using a transgenic mouse model. AB - Patients with type I diabetes lose immunologic tolerance to beta cell Ag and produce anti-self (beta cell) antibodies. We have examined mechanisms by which this self tolerance is lost using transgenic mice in which islet cells express human CD4. These mice are immunologically tolerant to this human protein; the tolerance appears to be characterized by the presence of self reactive B cells and nonresponsive T cells. Autoantibodies can be induced by immunization with CD4 in CFA; this autoantibody response is accompanied by minor peri-islet inflammation but diabetes is not induced. Tolerance can also be broken by provision of an independent covalently linked T cell epitope. Although this mimic can lead to the appearance of an autoantibody response, the autoimmune response can not be maintained by the endogenous Ag. We have also demonstrated that an inflammatory lesion leading to death of the CD4-containing beta cells may not be sufficient to break tolerance. These results have implications for potential mechanisms relating to the appearance of autoantibodies in patients with type I diabetes. PMID- 8432979 TI - Recombinase activating gene expression in thymic subpopulations. A transitional cell type has lost RAG-2 but not RAG-1. AB - We have used a highly sensitive Northern blot probing technique to examine RAG-1 and RAG-2 mRNA expression in unmanipulated murine thymocytes of various developmental phenotypes sorted by flow cytometry. We have found that neither RAG 1 nor RAG-2 are down-regulated until thymocytes reach the TCRhi stage. TCRhi, CD8+CD4+ cells have lost RAG-2 mRNA but continue to express significant levels of RAG-1 mRNA, providing molecular evidence that this cell type is transitional between the TCRlo, CD4+CD8+ and the TCRhi, CD4+CD8-, or CD4-CD8+ phenotypes. PMID- 8432981 TI - Molecular analysis of double isotype expression in IgA switching. AB - In this and previous studies we have shown that during the course of B cell isotype differentiation occurring in the CH12.LX B cell line, small numbers of cells appear that bear both membrane (m)IgM and membrane IgA. We have cloned relatively stable populations of such dual-bearing cells and have performed studies to determine their molecular status. In the study of one such subclone (CH12.LX.7.10), we show by primer extension that both mu and alpha mRNA contain identical VHDJH gene segments. In complementary studies of another such subclone (CH12.LX.7.13), we show using DNA restriction fragment analysis, that the C mu gene segment, but not the C alpha gene segment, is associated with the JH gene segment. Additionally, Northern blot analysis of productive message of this clone shows that both mu and alpha mRNA cohybridize to the same VH region-specific probe. Taken together, these data suggest that CH12.LX mIgM/mIgA dual-bearing cells occur in the absence of C mu gene segment deletion and that the mu and alpha mRNA transcripts are derived using an alternative mechanism such as transplicing or alternative splicing of a long RNA transcript. On the assumption that these clones are representative of mIgM/mIgA dual-bearing cells appearing during CH12.LX IgM to IgA isotype differentiation, these data support the idea that B cells simultaneously produce mu and alpha mRNA transcripts during one stage of IgA isotype switching. PMID- 8432980 TI - Clonal analysis of a human antibody response. II. Sequences of the VH genes of human IgM, IgG, and IgA to rabies virus reveal preferential utilization of VHIII segments and somatic hypermutation. AB - The construction of mAb-producing cell lines has been instrumental in dissecting the fine specificities and genetic makeup of murine antibodies to exogenous and self Ag. The analysis of the genetic composition of human antibody responses has been hampered by the difficulty in generating human mAb of predetermined class and specificity. Using B lymphocytes from three healthy subjects vaccinated with inactivated rabies virus vaccine, we generated nine human mAb binding to rabies virus and analyzed the genes encoding their VH regions. Six mAb (five IgG1 and one IgA1) were monoreactive and displayed high affinities for rabies virus Ag. The remaining three mAb (IgM) were polyreactive and displayed lower affinities for rabies virus Ag. Seven mAb (3 IgG1, the IgA1, and the three IgM) utilized VH gene segments of the VHIII family. The remaining two IgG1 mAb utilized gene segments of the VHI and VHIV families. Of the seven expressed VHIII family genes, three were similar to the germline VH26c gene, two to the germline 22-2B gene, one to the germline H11 gene, and one to the germline 8-1B gene. The expressed VHI and VHIV genes displayed sequences similar to those of the germline hv1263 and V71-4 genes, respectively. The VH genes of all but one mAb (mAb55) resembled those that are predominantly expressed by C mu + clones in human fetal liver libraries. When compared with known germline sequences, the VH genes of the rabies virus-binding mAb displayed variable numbers of nucleotide differences. That such differences resulted from a process of somatic hypermutation was formally demonstrated (by analyzing DNA from polymorphonuclear neutrophil of the same subject whose B lymphocytes were used for the mAb generation) in the case of the VH gene of the high affinity (anti-rabies virus glycoprotein) IgG1 mAb57 that has been shown to efficiently neutralize the virus in vitro and in vivo. The distribution, mainly within the complementarity determining regions, and the high replacement-to-silent ratio of the mutations, were consistent with the hypothesis that the mAb57-producing cell clone underwent a process of Ag-driven affinity maturation through clonal selection. The D gene segments of the rabies virus selected mAb were heterogeneous and, in most cases, flanked by significant N segment additions. The JH segment utilization was unbalanced and reminiscent of those of the adult and fetus. Four mAb utilized JH4, two JH6, two JH3, and one JH5; no mAb utilized JH1 or JH2 genes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8432982 TI - Purified beta-chain of MHC class II binds to CD4 molecules on transfected HeLa cells. AB - The initial event triggering the activation of Th cells occurs when the TCR interacts with antigenic peptide in the context of the MHC II on APC. Various T cell accessory molecules including CD4, CD28, and LFA-1 participate and facilitate the activation event. Although some evidence for the interaction of MHC II and CD4 is available, the site of MHC class II (alpha-chain, beta-chain, or both chains) for CD4 interaction has not yet been clearly defined. Results from different laboratories had indicated the involvement of alpha 1, beta 1, and beta 2 domains of MHC class II molecules in CD4 interaction. Recently, a conserved site of DR beta 2 domain has been identified that involves CD4 interaction that is analogous to MHC class I binding site for CD8 molecule. In this report, direct binding of affinity-purified HLA-DR2 dimer and its isolated alpha- and beta-chains to CD4 was studied using a CD4-transfected HeLa cell line. Preferential binding of the beta-chain and intact MHC II dimer to the CD4 transfected cells was observed and found to be specifically inhibited by anti-CD4 mAb. In contrast, the isolated alpha-chain of HLA DR2 did not show significant binding to CD4-transfected cells. Complexes of radiolabeled DR2 dimer or beta chain alone with an immunodominant epitope from myelin basic protein (83-102) did not show any further increase in binding of these molecules. Binding of the beta chain to CD4+ cells was markedly inhibited by a DR beta 1 peptide (35-46) and was partially inhibited by a DR beta 2 peptide (134-148) of MHC class II molecule. These results suggest the involvement of at least two conserved regions of the beta polypeptide chain of MHC class II in CD4 interaction. Because in our experiments transfected cells lack TCR molecules and the binding of DR2 to the CD4-transfected cells was unaffected by added antigenic peptide, it is possible that the interaction of MHC class II to CD4 is independent of TCR occupancy. PMID- 8432983 TI - V region diversity in human anti-insulin antibodies. Preferential use of a VHIII gene subset. AB - Data on structures used by human antibody repertoires are derived principally from lymphoid malignancies and from autoantibodies that often express VH genes from the developmentally regulated fetal repertoire. To determine whether human immune responses generated by exogenous Ag use a pool of VH genes distinct from the fetal repertoire, nucleotide and predicted amino acid sequences were determined for five anti-insulin B cell clones from a type I diabetic patient treated with human insulin. The data show that a set of VHIII genes is preferentially used by human anti-insulin B cells. Structural features indicate that these expressed VH are derived from germ-line genes that are not frequent in fetal repertoires and these genes have undergone Ag-driven somatic mutation. The preferential use of related VH segments contrasts with the BALB/c anti-insulin response, which uses multiple V genes elements largely unmutated from germ-line sequences. In addition, long CDRH3 structures in human anti-insulin mAb are generated by complex gene interaction mechanisms that are not seen in murine anti insulin mAb. Interestingly, similar potential insulin-binding structures are used by antibodies from both species. These findings suggest that human responses to exogenous insulin may express a limited number of VH genes and depend upon somatic mutation and complex D gene interactions in CDRH3 to expand the repertoire. Although these antibodies bind autologous insulin, VH gene usage and structural features that predominate in the response are not characteristic of the fetal repertoire. PMID- 8432984 TI - The rabbit neutrophil N-formyl peptide receptor. cDNA cloning, expression, and structure/function implications. AB - The rabbit neutrophil N-formyl peptide receptor (FPR) has been well studied for its ligand binding properties. Recent gene cloning experiments have established the existence of a subfamily of G protein-coupled receptors that share extensive sequence homology with the FPR, yet lack the capability of high affinity binding to FMLP. These findings prompted us to identify the structural requirement for formyl peptide ligand binding by delineation of the primary structure of the rabbit FPR. A rabbit neutrophil cDNA library was screened with a cloned human FPR cDNA probe and the insert of one positive isolate (B6) was sequenced. The 1268-bp cDNA insert encodes a peptide of 352 amino acids. Stably transfected L cell fibroblasts expressing the rabbit cDNA displayed specific binding of the ligand fMet-Leu-[3H]Phe with two affinities (Kd = 0.31 and 7.5 nM). Addition of the nonhydrolyzable guanosine triphosphate analogue, GTP gamma S, converted > or = 85% of the high affinity sites to the low affinity sites. FMLP induced mobilization of intracellular calcium in the transfected cells (EC50 = 0.5 nM), a response sensitive to pertussis toxin. FMLP stimulation desensitized the receptor such that subsequent stimulation with the same ligand produced a significantly reduced signal. These results indicate that the cloned rabbit receptor represents a high affinity FPR, and that FPR-mediated early signal transduction events can be fully reconstituted in transfected mammalian cells. The rabbit FPR sequence is 78% identical to that of the human FPR, and 68% identical to FPR2, a homologue of FPR with a low binding affinity (Kd > or = 400 nM) for FMLP. Analysis of the aligned sequences of these three proteins revealed that: 1) the amino termini and the second extracellular loops have the lowest sequence homology; 2) sequence in the intracellular domains that couple to G protein are highly conserved; and 3) the first and the third extracellular loops and their adjacent transmembrane domains of the FPR may contain residues essential for the high affinity binding of FMLP. PMID- 8432985 TI - Cytokine production in BALB/c mice immunized with radiation attenuated third stage larvae of the filarial nematode, Brugia pahangi. AB - BALB/c mice immunized with radiation attenuated third stage larvae of the filarial nematode Brugia pahangi are strongly immune to challenge infection. Investigation of the profile of cytokines secreted by spleen cells from immune mice stimulated in vitro with either parasite Ag or with Con A revealed high levels of IL-5 and IL-9 and moderate levels of IL-4. In contrast, secretion of IFN-gamma by spleen cells from immune animals was negligible. Spleen cells from control mice secreted low levels of all cytokines assayed. Levels of parasite specific IgE were significantly elevated in immune animals and a peripheral blood eosinophilia was observed, which exhibited a biphasic distribution. Our results are consistent with the preferential expansion of Th2 cells in immune animals and provide the basis for dissecting the means by which radiation attenuated larvae of filarial nematodes stimulate immunity. PMID- 8432986 TI - MHC class I expression on tumor targets inhibits natural killer cell-mediated cytotoxicity without interfering with target recognition. AB - NK cell-mediated killing is inversely proportional to the amount of MHC class I expression on certain tumor targets. Two hypotheses have been proposed to explain why class I-bearing targets are more resistant to NK cell-mediated lysis: 1) the presence of class I prevents NK cell recognition of a triggering molecule on the target cell surface, or 2) class I recognition transmits a separate inhibitory signal to the NK cell. To differentiate between these potential mechanisms, we have used cloned human CD16+/CD3- NK cells, the class I-deficient cell line C1R, and C1R cells expressing high levels of transfected HLA class I gene products. If class I expression blocks NK cell recognition of the targets, then proximal cell signaling events such as phospholipase C-mediated hydrolysis of membrane phosphoinositides should be decreased in the NK cells interacting with the class I transfectants. However, we found that increases in the level of target cell class I expressions did not decrease phosphoinositide turnover or calcium signaling in NK cells. We also examined the effect of treating HLA-transfected C1R cells with mAb specific for the transfected MHC class I gene product. If class I expression has a negative regulatory influence on NK cell activation, then treating the targets with anti-HLA mAb should block the transmission of this negative signal. Consistent with this notion, addition of anti-HLA mAb (either whole Ig or F(ab')2 fragments) led to increased lysis of the class I-transfected targets. In contrast, addition of isotype-matched mAb specific for other cell surface markers did not alter sensitivity to lysis. All of these results suggest that MHC class I expression on target cells can initiate inhibitory signals in NK cells without blocking access to target structures. PMID- 8432987 TI - Isolation from Trypanosoma cruzi-infected mice of CD8+, MHC-restricted cytotoxic T cells that lyse parasite-infected target cells. AB - Recent in vivo depletion studies in mice demonstrated that CD8+ T cells play a critical role in acute resistance to experimental Trypanosoma cruzi infections. As part of efforts to characterize these protective CD8+ T cell effector populations, we report here that splenic lymphocytes from mice chronically infected with T. cruzi can be induced to express high levels of cytolytic activity after stimulation in vitro with irradiated T. cruzi-infected macrophages. Cytolytic activity can either be detected using a nonspecific lectin dependent 51Cr-release assay or using 51Cr-labeled T. cruzi-infected target cells. Fresh splenocytes from chronically infected mice stimulated with T. cruzi infected macrophages exhibit relatively "promiscuous" killing activity inasmuch as significant lysis of both T. cruzi-infected and uninfected syngeneic and allogeneic cells is detected. However, subsequent rounds of in vitro stimulation lead to the expression of lytic activity that is T. cruzi Ag-specific and MHC restricted. Several short term in vitro maintained cytolytic T cell lines were shown to have mixed phenotypes by FACS analysis; approximately 50% to 75% of the cells in these populations were CD4-, CD8+, whereas 20% to 40% were CD4-, CD8-. Experiments in which effector cells were positively selected by adherence to anti CD8 mAb-treated plates confirmed that CD8+ T cell could exhibit Ag-specific cytolytic activity against T. cruzi-infected target cells. Efforts are under way to clone these CTL to test their in vivo function and to determine their Ag specificity. PMID- 8432988 TI - Antimetastatic vaccination of tumor-bearing mice with two types of IFN-gamma gene inserted tumor cells. AB - IFN-gamma genes were introduced through retroviral vectors into the high metastatic, low H-2Kb class I expressor, and poorly immunogenic 3LL-D122 clone. Two types of IFN-gamma infectants were isolated: IFN-gamma high secretors (128 to 256 IU/ml) and IFN-gamma non- or very low secretors (< 2 IU/ml). Both manifested high expression of MHC class I Ag. IFN-gamma secretors showed significant decrease in tumorigenicity and metastatic growth, whereas IFN-gamma nonsecretors retain tumorigenicity and were more metastatic than parental D122 cells. However, both groups, when inoculated in an irradiated form, induced similar high levels of CTL and protected mice to the same degree against a subsequent graft of parental cells. This indicates that enhanced expression of MHC class I and related genes caused by IFN-gamma is the major participant in CTL induction. Immunization of mice carrying an established tumor of parental D122 cells with IFN-gamma infectants is capable of almost completely preventing lung metastasis. Immunotherapy of tumor-bearing hosts is more effective when IFN-gamma secreting cells are used as immunogens, indicating that mechanisms, in addition to CTL, are stimulated by secreted IFN-gamma. Moreover, immunization with IFN-gamma high secretors of postoperative mice, carrying established micrometastases, almost completely cured these mice. Support for the participation of non-T cell effectors in the response to IFN-gamma secretors derives from the reduced tumorigenicity of these cells in CD1 nude mice. These data provide a rationale for the use of IFN-gamma gene-transferred tumor cells as a modality for cancer therapy. PMID- 8432989 TI - Catecholamines stimulate MHC class I, class II, and invariant chain gene expression in brain endothelium through different mechanisms. AB - Bovine brain microvessel endothelial cells in primary culture retain a differentiated phenotype reminiscent of the in vivo blood-brain barrier endothelium. The IFN-gamma-induced surface expression of MHC class II molecules on those cells is stimulated by catecholamines through a cAMP-independent mechanism. We report that both the induction of MHC class II molecule expression by IFN-gamma and its potentiation by isoproterenol, a catecholamine analog, are preceded by increases of steady-state levels of the corresponding mRNA. Similar results were obtained for the regulation of invariant chain expression. In addition, isoproterenol alone is able to increase class I mRNA levels, but, in contrast to what is observed for class II expression, this effect appears to be mainly mediated by cAMP. These studies demonstrate that, in bovine brain microvessel endothelial cells, catecholamines up-regulate MHC class I and class II Ag, as well as invariant chain with different kinetics and through different mechanisms and suggest that these regulatory effects occur at the transcriptional level. PMID- 8432990 TI - Induction of leukemia inhibitory factor in human synovial fibroblasts by IL-1 and tumor necrosis factor-alpha. AB - The cytokines, IL-1 alpha and TNF-alpha, induced a dose-dependent production of leukemia inhibitory factor (LIF) in cultured human synovial fibroblast-like cells, as measured by a radioreceptor competition assay. Significant levels of LIF were first detected in cell supernatants between 2 and 4 h after cytokine addition. Increases were also observed in LIF mRNA steady-state expression. Evidence is presented for down-regulation of the IL-1-induced LIF activity by an endogenous cyclo-oxygenase product(s); the glucocorticoid, dexamethasone, lowered the IL-1-induced LIF activity and mRNA expression. A synergistic effect was noted between the actions of IL-1 alpha and TNF-alpha, and between IL-1 and transforming growth factor-beta. IFN-gamma could not induce LIF formation in the synovial cells but inhibited the stimulatory effect of IL-1. These results suggest that cytokine-stimulated synovial fibroblasts may be a major source of intraarticular LIF production in the joints of patients with inflammatory arthritis. Synoviocyte-derived LIF may activate monocyte/macrophages in the lesions and may contribute to the bone changes and certain systemic manifestations in patients with inflammatory joint disease. PMID- 8432991 TI - Activation of human peripheral blood mononuclear cells by nitric oxide-generating compounds. AB - Recent work in this laboratory has identified immune-stimulatory properties of the oxidant hemin. In this study, we examined whether the nitrogen-based oxidant nitric oxide (NO) had inductive effects on human lymphocytes. We found that the NO-generating compounds sodium nitroprusside and S-nitroso-N-acetylpenicillamine rapidly enhanced the rate of glucose transport in resting human PBMC. In addition, NF-kappa B binding activity was induced by these agents as was the secretion of TNF-alpha. The data suggest that a cGMP-independent mechanism is involved as the cell permeant cGMP analogue, 8-Br-cGMP, had no effect in eliciting these inductive events. Activation of lymphocytes by these NO generating compounds may be mediated through the protein tyrosine phosphorylation signal transduction pathway. We found that membrane-associated protein tyrosine phosphatase activity was enhanced in PBMC treated with sodium nitroprusside or S nitroso-N-acetylpenicillamine and that the src family protein tyrosine kinase p56lck was activated in these cells. Inasmuch as p56lck activity is negatively controlled by tyrosine phosphorylation, its activation may be related to the enhancement of protein tyrosine phosphatase activity. 8-Br-cGMP had no effect on these enzymes. Taken together, these data suggest that NO may have immune stimulatory properties and may signal through a hitherto undescribed cGMP independent pathway. PMID- 8432992 TI - In vitro production of IL-6, IL-1 beta, and tumor necrosis factor-alpha by human embryonic microglial and neural cells. AB - The abilities of the different cells from human central nervous system (CNS) to produce IL-6, IL-1 beta, and TNF-alpha were tested in vitro using either cultures enriched in human embryonic microglial cells or primary cultures of human embryonic CNS cells. High amounts of IL-6, low amounts of IL-1 beta but no TNF alpha were detected in supernatants of microglial cells, kept either in FCS-free conditions or in FCS-containing medium. Moreover, IL-6 mRNA was also present in 45 to 55% of microglial cells cultured in the presence of FCS as visualized by in situ hybridization, whereas IL-1 beta mRNA remained undetectable. After prestimulation of microglial cells with LPS or IL-1 alpha, the percentage of cells labeled with an antisense IL-6 mRNA probe increased to 70% and hybridization with an antisense IL-1 beta mRNA probe became detectable. In contrast to this dyscoordinate production of cytokines by microglial cells, human monocytes, freshly isolated from blood and kept in the same culture conditions, produced high levels of the three cytokines tested. In primary cultures of human embryonic CNS cells, IL-6, IL-1 beta, and TNF-alpha were produced mostly or only by microglial cells because no IL-1 beta mRNA or IL-6 mRNA were detected in astrocytes, even after prestimulation with LPS or IL-1 alpha. Finally, IL-1 was the main inducer of IL-6 production because IL-1 alpha, but not LPS, induced a significant increase in IL-6 synthesis in cultures kept in FCS-free medium. However, in presence of FCS, LPS appeared to initiate a cascade reaction involving the production of IL-1 by microglial cells, acting as an autocrine loop to trigger IL-6 synthesis. PMID- 8432993 TI - IL-1 induces expression of monocyte chemoattractant JE in clonal mouse osteoblastic cell line MC3T3-E1. AB - Recent studies demonstrated that platelet-derived growth factor-inducible JE is an inflammatory cytokine that directs chemotaxis of monocytes, and is a homolog of monocyte chemoattractant protein-1, which is a human monocyte chemotactic factor. Migration and accumulation of monocyte lineage cells in bone tissue sites are very important for the recruitment of multinucleate osteoclasts, because the origin of osteoclasts is derived from monocyte lineage cells in hemopoietic cells. Because IL-1 is a potent regulator in bone remodeling, we examined whether IL-1 beta induces JE expression in a clonal mouse osteoblastic cell line, MC3T3 E1. Significant chemotactic activity for human monocytes was detected in conditioned medium of the cells at 6 h after initiation of IL-1 beta treatment, and the chemotactic activity increased in both a culture time- and dose-dependent manner. The peak of the chemotactic activity in the conditioned medium was observed in fractions corresponding to a m.w. of 26 kDa when the conditioned medium was fractionated by gel filtration. The chemotactic activity in the peak fraction was completely neutralized by antiserum specific for JE protein. And the JE gene product in the conditioned medium was detected as a microheterogeneous protein with a m.w. of 21 to 33 kDa by immunoprecipitation with the specific antiserum. IL-1 beta induced a maximal JE gene expression in the cells at 3 h after initiation of the cytokine treatment. This significant expression was observed when IL-1 beta was used at a concentration of 10 U/ml, and the expression was dose dependent. The run-on assay showed that the cytokine-induced JE gene expression increased at the transcriptional level. IL-1 beta and TNF alpha acted synergistically to stimulate JE gene expression in the cells. Expression and product of the JE gene were also observed in an osteoblast enriched cell population prepared from mouse calvariae. These results suggest the possibility that osteoblastic cells can participate in osteoclast recruitment via the JE gene product. PMID- 8432994 TI - Overlap of the anti-Sm and anti-DNA responses of MRL/Mp-lpr/lpr mice. AB - Autoantibodies specific for the Sm ribonucleoprotein are spontaneously produced in patients with SLE and in mice of the MRL mouse strains. We have previously reported the characterization of the clonality and V region gene use of 41 MRL/Mp lpr/lpr (MRL/lpr)-derived B cell hybridomas selected for Sm binding. In this report, we show that many of the expressed V genes of these hybridomas are also expressed by anti-DNA hybridomas of MRL/lpr mice. Moreover, the anti-Sm hybridomas from nine clonal groups produce antibodies that bind ssDNA, and those of five clones produce antibodies that also bind dsDNA. Sm/DNA-specific hybridomas, but not Sm-only-specific hybridomas, have a higher than expected content of arginine residues in CDR3 of the H chain, similar to MRL/lpr hybridomas selected on the basis of DNA binding. One clone displays intraclonal differences in DNA binding, inasmuch as the most extensively mutated members produce antibodies that are able to bind dsDNA and have a higher affinity for ssDNA than the least mutated members of this clone. Thus, DNA appears to be a selecting Ag in this response. These data indicate an overlap in the anti-Sm and anti-DNA autoimmune responses in MRL mice that may have implications for the activation of anti-Sm B cells, and for defining the spectrum of Ag targeted in SLE. PMID- 8432996 TI - Antibodies to Trypanosoma cruzi express idiotypic patterns that can differentiate between patients with asymptomatic or severe Chagas' disease. AB - Immunization of rabbits with pools of immunoaffinity-purified anti-Trypanosoma cruzi epimastigote antibodies derived from patients with different clinical forms of Chagas' disease induces antiidiotypic sera that can distinguish between anti epimastigote antibodies from patients with asymptomatic (indeterminate (IND)) or severe (cardiac (CARD)) Chagas' disease. These idiotypically different anti-EPI antibodies from patients with the different clinical forms do not differ in their anti-epimastigote activities or isotypes. Analysis of immunoaffinity purified antibodies from individual chagasic patients by specific competitive ELISA generally confirms that Id-specific rabbit antisera can differentiate the clinical forms of the source of the antibodies. Based on these data, immunoaffinity-purified antibodies from patients share many Id with those from IND patients, although antibodies from IND patients express much lower levels of the distinctive Id characteristic of CARD patients. Reduction and alkylation of antibodies from IND patients reduces somewhat, but does not abolish, the ability of their Id to be recognized idiotypically, and to effectively inhibit in competitive ELISA. In contrast, reduction and alkylation of antibodies from CARD patients almost completely eliminates the ability of their predominant Id to be either recognized by, or inhibit, the appropriate systems. These data imply that the expression of the major Id that define CARD patients by these serologic anti Id systems is largely dependent on the tertiary conformation of the Ig molecule. This agrees with our earlier studies on the respective differential abilities of CARD vs IND Id to stimulate anti-Id T cells by direct stimulation vs processing and presentation mechanisms. PMID- 8432995 TI - V region gene analysis of anti-Sm hybridomas from MRL/Mp-lpr/lpr mice. AB - Anti-Sm autoantibodies are unique to SLE, but are present in only 25% of patients with this disease. This response also occurs at a similar frequency in mice of the autoimmune MRL strains. Previous analyses of the anti-Sm response in these mice indicate that its occurrence is controlled by stochastic events, and suggest that Sm is the driving Ag. To further elucidate the role of Ag in this response, and to test the hypothesis that the 25% incidence is due to a requirement for particular Ig gene rearrangements or somatic mutations, we have analyzed the specificity and V-region gene sequences of 41 anti-Sm B cell hybridomas derived from nine anti-Sm-positive MRL/Mp-lpr/lpr mice. The majority of hybridomas are specific for the D peptide of the Sm particle. Hybridomas of independent origin express unique VH/V kappa combinations with diverse junctional sequences and are variable in the extent of somatic mutation. Thus, the response does not appear to be dependent upon the occurrence of a rare Ig gene rearrangement or specific somatic mutation. The response exhibits restriction in JH and VH gene use, and in individual mice is oligoclonal, suggestive of Ag selection. In the few B cells for which mutations can be identified, the evidence for selection of mutant B lymphocytes, based on patterns of mutation, is ambiguous. However, there is remarkably little intraclonal diversity, suggesting that the overall mutation rates in these clones are low. PMID- 8432997 TI - Anti-CD3:anti-IL-2 receptor bispecific monoclonal antibody. Targeting of activated T cells in vitro. AB - T cells are major mediators of graft rejection and many autoimmune diseases. During the Ag recognition process, T cells often become activated. We tested the hypothesis that an anti-CD3:anti-CD25 (CD3,25) bispecific mAb (BSMAB) can effectively and selectively target activated T cells. By flow cytometric analysis, the CD3,25 BSMAB was shown to bind avidly to activated T cells that coexpress CD3 and CD25 (p55 chain of the IL-2R), achieving higher levels than the parent anti-CD3 and anti-CD25 mAb. It bound only weakly to unstimulated T cells. The CD3,25 BSMAB effectively redirected CTL to lyse CD25-bearing PHA-stimulated T lymphoblasts and the IL2-dependent CTLL tumor cell line in chromium release assays. It was highly effective in blocking MLR as shown by inhibition of [3H]TdR incorporation. However, the CD3,25 BSMAB has a low potential to activate resting T cells, as it induced only minimal [3H]TdR incorporation even in the presence of exogenous IL-2. In the absence of exogenous IL-2, the CD3,25 BSMAB was unable to induce [3H]TdR incorporation. In contrast, the parent anti-CD3 mAb induced a high degree of incorporation. In summary, the CD3,25 BSMAB selectively targets activated CD25-expressing T cells and lymphomas although maintaining a low activation potential for unstimulated T cells, potentially advantageous properties that can be exploited for immunotherapy. PMID- 8432998 TI - Pigmentation genes: the tyrosinase gene family and the pmel 17 gene family. AB - We propose that at least two families of genes regulate the melanin biosynthesis. The first is the tyrosinase gene family, which is comprised of tyrosinase (c locus), gp75 (b locus) and DOPAchrome tautomerase (slt locus). The second is the pmel 17 gene family, which is composed of pmel 17 (putative si locus) and chicken melanosomal matrix protein (MMP) 115. It appears that the tyrosinase gene family regulates melanin synthesis in the proximal steps of the melanin biosynthetic pathway and the pmel 17 gene family might be important at distal steps of the pathway. PMID- 8432999 TI - Expression of tyrosinase gene in transgenic mice: programmed versus non programmed expression. AB - The transgenic experiment is a useful tool for the study of cell type-specific expression of genes during embryogenesis. We constructed a minigene, mg-Tyrs-J, by fusing a tyrosinase cDNA, Tyrs-J, with the 5' upstream region of genomic deoxyribonucleic acid (DNA) clone, G3L, and microinjected this minigene into fertilized eggs from albino BALB/c mice. It was expected that a melanin pigment would be produced and deposited in the melanosomes of melanocytes of BALB/c mice if the mg-Tyrs-J was expressed in a cell type-specific manner. In the transgenic mice, melanin pigments were observed only in melanocytes and in hair shafts of hair follicles, and in the choroid and pigmented epithelium of the eyes. However, Southern blot analysis of the genomic DNA of the transgenic mice showed that the transgene was present in all tissues examined. These results apparently indicate that the introduced transgene is integrated into a chromosome(s) and distributed among somatic cells, whereas the gene is expressed exclusively in melanocytes, i.e., the transgene is expressed in a cell type-specific manner. Some founder mice were crossed with BALB/c albino mice to establish transgenic lines. Each line and subline shows inherited characteristic phenotypes; in particular, offsprings from two founders exhibited a patched phenotype. The possible mechanism of this interesting expression of these transgenes is discussed in comparison with the results of other investigators who observed both programmed and non-programmed expression of the tyrosinase gene in transgenic mice. PMID- 8433000 TI - Functional analysis of the tyrosinase gene and brown-locus protein gene promoters. AB - Tyrosinase is a rate-limiting enzyme of melanin biosynthesis and the brown (b) locus protein is responsible for the formation of black melanin rather than brown. To identify the cis-acting element(s) required for pigment cell-specific gene transcription, we analyzed the promoter function of two pigment cell specific genes encoding mouse tyrosinase and b-locus protein using a cell-free transcription system prepared from mouse melanoma cells. Functional and structural analysis of both gene promoters reveals that three elements are conserved in both genes at equivalent positions, suggesting that these elements may be responsible for pigment cell-specific transcription. We discuss possible mechanisms for pigment cell-specific expression of the tyrosinase and b-locus protein genes. PMID- 8433001 TI - Tyrosinase gene transcription and its control by melanogenic inhibitors. AB - The levels of tyrosinase mRNA and tyrosinase activity were analyzed in two amelanotic melanoma cell lines, D1(178) (hamster) and G-361 (human). Neither tyrosinase mRNA nor tyrosinase activity were detected in D1(178) cells. On the other hand, both tyrosinase mRNA and weak tyrosinase activity were detected in G 361 cells. Assuming that the different types of melanogenic inhibitors affected melanogenesis in these two amelanotic melanoma cells in different manners, we performed a screening of melanogenic inhibitors in these two cell lines. As an isolated tyrosinase suppressive melanogenic inhibitor, ascorbic acid and glutathione were identified from D1(178) cells and G-361 cells, respectively. Furthermore, lactic acid was identified from D1(178) cells as an isolated tyrosinase non-suppressive melanogenic inhibitor. B-16 mouse melanotic melanoma cells were depigmented by treatment with lactic acid. The melanogenesis suppression by lactic acid in B-16 cells was found to be due to inhibition of tyrosinase gene expression. PMID- 8433002 TI - Regulatory mechanisms of melanogenesis: beyond the tyrosinase concept. AB - The last decade has witnessed a quantum jump in our knowledge of the chemistry of melanogenesis and the emergence of some understanding as to how the chemical and enzymatic activities are integrated and regulated at cellular level. To an unusual extent, most of these advances stemmed from a molecular approach involving direct analysis of natural melanins coupled with studies of the chemical reactivity of the putative intermediates under biologically relevant conditions. Thus, bit by bit it has been possible to reconstruct in vitro the overall chemical activity of melanocytes, and to identify a number of regulatory factors other than tyrosinase. This and other approaches, especially the molecular biology of the pigment-related genes, have radically changed and expanded the traditional concept of melanogenesis far beyond the boundaries of the Raper-Mason pathway. Recently, I suggested an improved scheme of melanogenesis accounting for the formation of melanins and related products of melanocyte activity. The present contribution surveys some verifications of the predictions, and certain new break-throughs that have been made in the understanding of the regulatory steps after the dopaquinone stage. It also aims to provide an overview of what is presently known about the structure of the melanin polymers, and to draw attention to some problems pertaining to the definition and classification of the various types of pigments that can be found in epidermal tissues. PMID- 8433003 TI - Dynamics of melanogenesis intermediates. AB - The course of melanogenesis in (malignant) melanocytes is determined by several relatively independent metabolic processes such as tyrosine uptake and compartmentation, the activity of tyrosinase, and the capacity of melanosomes to produce and store melanin. There is experimental evidence that tyrosine is transported across the cell membrane with a Na(+)-independent L transport system. Tyrosine designated for melanogenesis is probably localized in compartments different from those for protein synthesis. The maturation and subsequent activation of tyrosinase occurs primarily in the Golgi-associated endoplasmatic reticulum and coated vesicles. In these locations, the interaction between tyrosine and tyrosinase has some limitations because no melanin polymer can be detected in these structures. Nevertheless, the coated vesicles were shown to contain unpolymerized monomeric indols. Individual skin types differ in their ability to produce mature, fully pigmented, melanosomes. Whereas eumelanin content in melanocytes corresponds to the phenotypic appearance of the skin, the formation of pheomelanin varies considerably. Precursors of pheomelanin, such as glutathione and cysteine, are responsible for scavenging potentially toxic quinoid products of melanogenesis that escape from melanogenic compartments. Pheomelanogenesis can therefore be considered as one of the protective mechanisms of melanocytes. Significant leakage of reactive intermediates of melanogenesis may occur from aberrant melanosomes and explain the frequent incidence of necrosis in melanoma tissue. The presence of O-methylated derivatives of 5,6 dihydroxyindole (5,6DHI) and 5,6-dihydroxyindole-2-carboxylic acid (5,6DHI2C) in medium of melanoma cell cultures gives evidence of intracellular O-methylating ability. The O-methylation of o-dihydroxyphenols and indols by catechol-O methyltransferase localized in microsomes and cytoplasma prevents their oxidation to reactive quinones. It is suggested, however, that this protective mechanism can be unreliable because catechol-O-methyltransferase can be inactivated by its oxidated substrates. PMID- 8433004 TI - High-performance liquid chromatography (HPLC) analysis of eu- and pheomelanin in melanogenesis control. AB - Two types of melanogenesis, eumelanogenesis and pheomelanogenesis, can be switched from one type to another under certain physiologic or pathologic conditions. To study the regulation of melanogenesis, we developed a high performance liquid chromatography method to analyze quantitatively the contents of eu- and pheomelanin in tissue samples without any isolation procedures. The rationale is that permanganate oxidation of eumelanin yields pyrrole-2,3,5 tricarboxylic acid, which may serve as a quantitatively significant indicator of eumelanin, whereas hydriodic acid hydrolysis of pheomelanin yields aminohydroxyphenylalanine as a specific indicator of pheomelanin. The method has been successfully applied to the analysis of eu- and pheomelanin not only in synthetic melanins, melanosomes, hair, feathers, and melanomas, but also in human epidermis and cultured melanocytes. These studies indicate that there exists an inverse relationship between the contents of eu- and pheomelanin. We propose that the switching between the two types of melanogenesis is mainly controlled by the level of tyrosinase activity: higher activity leads to eumelanogenesis and lower activity leads to pheomelanogenesis. When tyrosinase activity is low, dopaquinone, a reactive intermediate in melanogenesis, is quantitatively converted to glutathionyldopa, which gives rise exclusively to pheomelanin. When tyrosinase activity is high, an excess of dopaquinone is produced, which results in the inactivation of glutathione reductase and gamma-glutamyl transpeptidase, enzymes essential for pheomelanogenesis. These biochemical events eventually leads to eumelanogenesis. PMID- 8433005 TI - Detection of eumelanogenic and pheomelanogenic melanosomes in the same normal human melanocyte. AB - Ellipsoid and spheroid melanosomes similar to those found in the hair matrix melanocytes of eumelanic C57BL mice and pheomelanic Ay mice, respectively, have been shown to coexist in the same human melanocyte. The difference in the three dimensional ultrastructure of these melanosomes of the human hair matrix melanocyte has been determined by high-voltage transmission electron microscopy using a goniometer. By energy-dispersive X-ray spectroscopy, sulfur, one of the main characteristic chemical properties of pheomelanin, is detected in a significant amount in each spheroid melanosome, but is absent in ellipsoid melanosomes. Furthermore, the internal structure of the spheroid melanosomes is dissolved by treatment with 0.5 N NaOH solution, whereas the ellipsoid melanosomes are not affected. We proposed that in normal human melanocytes pheo- and eumelanogenesis occurs in spheroid and ellipsoid melanosomes, respectively. PMID- 8433006 TI - White mutants in mice shedding light on humans. AB - In this article we describe the rapid advances made in the molecular genetics of three inherited pigmentation disorders: albinism, piebaldism, and vitiligo, all of which throw light on normal pigment cell function. The focus is on studies in mice, with comparison of data in humans. The critical role of tyrosinase (c-locus or human tyrosinase protein) in normal pigmentation and albinism has been reinforced by the cloning and identification of mutations in tyrosinase and two other melanocyte-specific oxidoreductases structurally related to but functionally different from tyrosinase: the (b) brown-locus protein/gp75/catalase B and dopachrome tautomerase. Each possesses a distinct enzyme activity and yet the three share homology in strategic regions. Most of the point mutations that reduce or abrogate the respective enzyme activities are located in those regions. Tyrosinase-negative albinism is caused only by defects in tyrosinase. A locus for human tyrosinase-positive albinism has been recently mapped to chromosome 15q11.2 ->q12, at a gene identified in mice as pink-eyed dilution. On the other hand, several genes encoding proteins critical for the proliferation of melanocytes are known to control the piebald phenotype. So far identified are two membrane receptor tyrosine kinases, c-Kit and PDGF-R/alpha, and the ligand for c-kit, MGF (mast-cell growth factor, also known as stem-cell factor, c-Kit-ligand, or steel factor). Mutations in W/c-kit (white spotting), Ph/Pdgfr/a (patch), and Sl/MGF (steel), lead to a reduction in receptor kinase activity and failure of melanocytes to thrive and reach the skin during embryogenesis. Finally, mouse mutant models suggest at least two possible causes for vitiligo, a progressive loss of pigmentation that occurs after birth. In one mutant, the Blt (light) mouse, the cyclic death of hair melanocytes may be due to the toxicity of intermediates and byproducts of melanogenesis in the presence of a dysfunctional b-locus protein. In the other model, the "vitiligo mouse," in which the allele vit has been assigned to the microphthalmia (mi) locus, the loss of melanocytes may be caused by defective signal transduction, because in addition to vitiligo mivit/mivit mice have extensive piebaldism. PMID- 8433007 TI - Tyrosinase gene mutations causing oculocutaneous albinisms. AB - Since the first report of a mutation in the tyrosinase gene that causes tyrosinase-negative oculocutaneous albinism (OCA), more than 25 alleles with a different mutation in patients with three types of OCA, i.e., tyrosinase-negative OCA (type IA), yellow-mutant OCA (type IB), and temperature sensitive OCA (type ITS), have been found in several laboratories. The mutated alleles are presently classified into three types. The first and the second group of alleles, termed t- and y, produce tyrosinases with no enzyme activity and with very low activity, respectively. The third, termed ts, produces temperature-sensitive tyrosinase with very low activity at 35 degrees C, but with no activity at temperatures greater than 35 degrees C. Various combinations of these alleles result in tyrosinase-negative (t-/t-), yellow mutant (y/y, y/t-, y/ts), or temperature sensitive (ts/t-, ts/ts) OCA. PMID- 8433008 TI - Selective increase of the alpha subspecies of protein kinase C and inhibition of melanogenesis induced by retinoic acid in melanoma cells. AB - Retinoic acid (RA) has been shown to inhibit melanogenesis in B16 mouse melanoma cells (B16 cells). On the other hand, it has been reported that RA increases protein kinase C (PKC) activity in these cells. Further investigation was carried out to identify the PKC subspecies expressed in B16 cells and to examine the changes in the level of each PKC subspecies by RA treatment. Hydroxyapatite column chromatography, immunoblot analysis, and kinetic analysis have shown that B16 cells express the alpha subspecies of PKC. Northern blot analysis has indicated that these cells normally express mRNA for the alpha, delta, epsilon, and zeta subspecies. Upon treatment of B16 cells with 1 microM RA for 48 h, both the activity of the alpha-subspecies and the level of mRNA for the alpha subspecies were increased, resulting in the decrease of melanin polymer formation and tyrosinase activity. Neither the enzyme activities nor mRNA for the beta and gamma subspecies were detected in either the RA-treated or untreated cells. The levels of mRNA for the delta, epsilon, and zeta subspecies were not altered by RA treatment. The demonstration of a selective increase of the alpha subspecies of PKC is a unique finding. PMID- 8433009 TI - Hydrogen peroxide as an inducer of elevated tyrosinase level in melanoma cells. AB - The effects of systems generating active oxygen species (superoxide anion, hydrogen peroxide, hydroxyl radical) on tyrosinase have been studied in cultured human melanoma cells. Tyrosinase activity was determined by measuring the quantity of 5-S-L-cysteinyl-L-dopa (5-S-CD) formed in the presence of D,L-dopa and L-cysteine. In some experiments, the enzyme protein was determined by radio immunoassay [RIA]. Exposure of cells to xanthine/xanthine oxidase or glucose/glucose oxidase resulted in a dose-related elevation of tyrosinase. Catalase, but not superoxide dismutase, prevented this increase indicating that hydrogen peroxide may be the agent responsible for the action, whereas superoxide anion is not involved. Hydroxyl radicals formed by the Haber-Weiss or Fenton type reactions were not found to produce elevation of tyrosinase. Catalase determinations showed no enzyme in the medium but a high concentration in the cells. Inhibition of intracellular catalase by 3-amino-1,2,4-triazole caused an increase in the tyrosinase level. The effects of dopac, xanthine/xanthine oxidase, and glucose/glucose oxidase all producing hydrogen peroxide, and increasing tyrosinase, were enhanced by the inhibition of catalase. It is concluded that hydrogen peroxide, formed by the systems, accounts for the elevation of tyrosinase level. When tyrosinase activities determined by 5-S-CD formation were compared to enzyme amounts found by RIA, the ratios of these values were always constant. This fact indicates that the increase in the tyrosinase activities was not due to an activation of the enzyme, but mirrored the quantities of enzyme protein present in the samples. On the basis of our findings, it is assumed that hydrogen peroxide is a regulator of tyrosinase in normal melanocytes and melanoma cells. PMID- 8433010 TI - Appearance of tumorous phenotypes in goldfish erythrophores transfected with ras, src, and myc oncogenes and spontaneous differentiation of the transformants in vitro. AB - When goldfish erythrophores isolated from the skin by tissue digestion and centrifugation in a Percoll density gradient were transfected in a monolayer culture with v-Ha-ras or v-src oncogene either singly or in combination with v myc by means of calcium phosphate-DNA co-precipitation, there appeared a certain number of transformants manifesting a chromatoblast-like profile and tumorous phenotypes as seen in the capability for unlimited growth, and piling-up in a monolayer-culture or colony formation in semi-solid soft agar. After successive growth in vitro for longer than one month which was scarcely observed with the erythrophores, the vast majority of such transformants began to differentiate into erythrophores and ceased proliferation spontaneously. The onset of their differentiation was ascertained by the deposition of marker pteridine pigments. None of the transformants differentiated into melanophores or iridophores or other neural crest derivatives as seen in goldfish erythrophoroma cells. Little difference was observed in their transforming efficiency (0.2-0.3 transformants/micrograms DNA) between the combinations of oncogenes applied but a tendency was noted that cells transfected with ras or src in combination with myc developed the capacity to grow for a longer period and differentiated at a later stage than those transfected solely with ras or src. One cell line (ESM-1) derived from the erythrophores transfected with src/myc grew successively over nine months, indicating its acquisition of immortality. The expression of the transfected oncogenes in this cell line was examined in comparison with the erythrophoroma cells by Western and Northern blot analyses. PMID- 8433011 TI - Differences in subcellular distribution of catechol-O-methyltransferase and tyrosinase in malignant melanoma. AB - The activities of catechol-O-methyltransferase (COMT) and tyrosinase were measured in subcellular fractions obtained from transplantable melanotic and amelanotic hamster melanoma. The results showed that there was a substantial difference between the localization of these enzymes. Whereas tyrosinase was localized mainly in the large granule fraction, the highest COMT activity was found to be in fractions abundant in microsomal structures. As expected, subcellular fractions obtained from amelanotic melanoma contained low or undetectable tyrosinase activity. On the other hand, the same fractions exhibited higher COMT activity than those from the pigmented tumor. Relatively low specific activity of COMT in fractions containing coated vesicles does not support the idea that this enzyme could be responsible for the inhibition of melanin polymerization in these structures. Because melanogenic intermediates, such as 5,6-dihydroxyindole and 5,6-dihydroxyindole-2-carboxylic acid, are compartmentalized within membraneous structures, the preferential localization of COMT in cytosol and cytosolic membrane network might be advantageous for a detoxification role in (melanotic) melanocytes that produce dihydroxyindoles. PMID- 8433012 TI - Abnormalities in HLA class I antigen expression by melanoma cells: structural characterization and functional implications. PMID- 8433013 TI - Exploitation of pigment biosynthesis pathway as a selective chemotherapeutic approach for malignant melanoma. AB - Human malignant melanoma represents a difficult therapeutic challenge to both medical scientists and practicing physicians. However, the biologic uniqueness of the tumor may provide opportunities for exploitation in therapeutics. This study proposed to undertake a systemic approach to the chemotherapy of malignant melanoma based upon the uniqueness of pigment-cell metabolic pathway pertaining to conversion of tyrosine and dopa with subsequent formation of melanin by tyrosinase and its related enzymes. The sulphur homologue of tyrosine, cysteinylphenol (CP), its amine derivative, cysteaminylphenol (CAP), and their N acetyl and alpha-methyl derivatives have been synthesized and tested in in vivo and in vitro melanocytotoxicity and antimelanoma effects. These phenolic thioethers (PTEs) and phenolic thioether amine (amides) (PTEAs), which are substrates of tyrosinase, showed significant cytotoxicity that is selective to melanocytes and melanoma cells. Most previous attempts to impair the melanin pathway as a therapeutic strategy have been of limited success because they have been directed to catecholic compounds that are unstable and insufficient in lethality at physiologically tolerable doses. By contrast, our approach relies on phenolic compounds, PTEs and PTEAs, which are more stable than catechols and become toxic only after oxidation by tyrosinase. We found PTEA as the most promising agent for the future development of chemotherapeutic agents. The possible biologic, chemical, and pharmacologic reactions of these synthetic compounds within the melanoma cells are studied and discussed. PMID- 8433014 TI - The role of interferon-gamma in the treatment of visceral and diffuse cutaneous leishmaniasis. AB - Traditionally, the mainstay of visceral and diffuse cutaneous leishmaniasis therapy has been pentavalent antimony, with pentamidine and amphotericin B reserved for refractory cases. Interferon-gamma (IFN-gamma) in combination with pentavalent antimony has been used successfully in treating patients refractory to pentavalent antimony and in patients with previously untreated visceral leishmaniasis (39 total). In addition, 6 patients with diffuse cutaneous leishmaniasis have been treated with combination IFN-gamma and antimony therapy. Preliminary experience with these patients indicates that IFN-gamma is a useful adjunct therapy for severe or refractory cases of visceral leishmaniasis; however, the potential of IFN-gamma in treating diffuse cutaneous leishmaniasis cannot be assessed as current clinical experience is too limited. PMID- 8433015 TI - Recent advances in cytokine therapy in leprosy. AB - Lepromatous leprosy is characterized by a selective anergy to Mycobacterium leprae and its antigens. The inadequate immune response and the resulting reduced interferon-gamma (IFN-gamma) production lead to a lack of macrophage activation and unrestricted bacterial growth. Purified protein derivative of tuberculin induced a normal local immune response in many lepromatous leprosy patients. Interleukin-2 induced an accelerated equivalent of an antigen response in the skin. In both, monocytes and T cells were recruited, and changes in keratinocytes, including expression of major histocompatibility complex class II antigens, were induced. Skin macrophages appeared to be activated and bacteria were eliminated. Similar effects were generated by IFN-gamma, a more distal molecule in the immune response. Cytokine treatment induced large amounts of tumor necrosis factor-alpha, which is toxic in this context but can be selectively down-regulated by thalidomide without interfering with other monocyte cytokines necessary for normal immune function. PMID- 8433016 TI - How cytokines signal messages within cells. AB - The intracellular signaling pathways used by cytokines to modulate the activity of immune effector cells have been the focus of intensive research. Cytokines interact with specific receptors on the plasma membrane, and this information is transduced into internal signals, often involving a cascade of kinases. These signals activate substrate proteins that serve as effectors within the cell. A number of protein kinase C substrates have been characterized. The function of one of these substrates, known as MARCKS (myristoylated alanine-rich C kinase substrate), appears to be important to the control of macrophage and neutrophil motility and may partially explain the modes of action of tumor necrosis factor and interleukin-8. PMID- 8433017 TI - Modulation of host defenses with interferon-gamma in pediatrics. AB - One of the most consistent defects in the neonate's host defense system is in the ability of polymorphonuclear leukocytes (PMNL) to move in a unidirectional fashion towards a chemotactic stimulus. Such impaired chemotaxis can be an important contributor to life-threatening neonatal infection. In vitro studies suggest that preincubation of PMNL from neonates with recombinant human interferon-gamma (rIFN-gamma) can enhance chemotactic responses. No other recombinant human cytokine except granulocyte colony-stimulating factor improved chemotaxis of PMNL from neonates. Similarly, pretreatment with rIFN-gamma has been shown to improve in vitro neutrophil chemotaxis in cells obtained from patients with hyperimmunoglobulinemia E (Job's) syndrome. These results suggest the need for controlled trials of rIFN-gamma in pediatric patients who are uniquely susceptible to tissue and pulmonary infections. PMID- 8433018 TI - Conventional versus interferon-gamma therapy in chronic granulomatous disease. AB - Chronic granulomatous disease is a rare, genetically heterogeneous group of disorders in which NADPH oxidase deficiency severely hampers the ability of phagocytes to kill ingested microorganisms. Characterized by recurrent pyogenic infections with granuloma and abscess formation, the disease appears in childhood and may be fatal. Conventional therapy consists of prophylactic trimethoprim sulfamethoxazole and aggressive infection control measures. Interferon-gamma (IFN gamma) has been shown in vitro and in vivo to correct alterations of oxidative metabolism. In the most recent multicenter study, IFN-gamma was efficacious in reducing the frequency of severe infections; however, at odds with previous results, this effect appeared to be due to some mechanism other than improvement in respiratory burst function. Although further studies are needed to elucidate the mechanisms of IFN-gamma's action, it appears to have potential application in many infectious diseases. PMID- 8433019 TI - Evaluation of CT images, tumour response and prognosis after thermoradiotherapy for deep-seated tumours. AB - Thermoradiotherapy was applied for the treatment of deep-seated tumours in 41 patients. Low-density area (LDA) on CT images which appeared or expanded within the tumour after treatment was evaluated. Derived conclusions are as follows: (1) of 41 patients, LDA newly appeared or expanded in 24; (2) change of density was related closely with size of a tumour, histological characteristics of the tumour and heating condition; (3) histologically, LDA consisted of coagulation necrosis and tumour cells at the peripheral wall were highly degenerated; (4) a greater extent of LDA indicated the increasing possibility of local control; (5) probability of survival for patients with an increase of LDA was significantly superior to those without changes of LDA; (6) LDA may be a good landmark for judgement of the prognosis of a patient treated by thermoradiotherapy; and (7) new criteria of treatment effectiveness including density changes were proposed. PMID- 8433020 TI - Effects of hyperthermia on the metabolism of 5-fluorouracil in vitro. AB - The effects of hyperthermia (38-42 degrees C) on the metabolism of 5-fluorouracil (5-FU) were examined using Ehrlich tumour cells (E-cells) and Sarcoma-180 cells (S-180 cells) in vitro. A temperature-dependent elevation of the intracellular concentration of 5-FU was observed in both types of tumour cell after incubation with 5-FU. The levels of 5-fluorouridine (FUR) and 5-fluoro-2'-deoxyuridine (FdUR), which are active metabolites of 5-FU, increased significantly after treatment of cells with 5-FU and hyperthermia. The highest concentrations of these active metabolites were found when the cells were incubated at 39 degrees C. The levels of alpha-fluoro-beta-ureido-propionic acid (FUPA) and F-beta alanine, which are inactive catabolic metabolites of 5-FU, also increased when the cells were incubated at 39 degrees C. The percentage inhibition of thymidilate synthetase (TS) activity remained high (about 60-70%) at 39 degrees C for 240 min. These results suggest that the optimal temperature for potentiating the intracellular metabolism of 5-FU, in terms of both activation and inactivation, is 39 degrees C in vitro. PMID- 8433021 TI - Cytoskeletal thermotolerance in NRK cells. AB - We investigated the effect of heat shock on the cytoskeletons (actin stress fibres, intermediate filaments and microtubules) and the relation between thermotolerance of cytoskeletons and thermotolerance as defined by clonogenic survival in normal rat kidney (NRK) cells. Upon heating at 45 degrees C for 15 min, almost all actin stress fibres were disrupted. During the recovery period after heat shock the stress fibres were reorganized rapidly and returned to their preheated state by 16 h. When the cells were heated again at 45 degrees C for 15 min, the disruption of stress fibres was less severe, indicating thermotolerant state of stress fibres. However, the thermotolerant state of stress fibres induced by prior treatment with sodium arsenite or by heating at 42 degrees C for 2 h was less evident than that induced by prior heat shock at 45 degrees C. The intermediate filaments in NRK cells were very heat-resistant; no apparent changes were observed even after heat shock at 45 degrees C for 60 min, and prior conditioning treatments could not induce thermotolerance of microtubules. All prior conditioning treatments could induce heat shock proteins and thermotolerance as defined by clonogenic survival. From these results it is suggested that there is no correlation between cytoskeletal thermotolerance and either heat shock protein level or thermotolerance as defined by clonogenic survival in NRK cells. PMID- 8433022 TI - Heat-induced unresponsiveness of heat shock gene expression is regulated at the transcriptional level. AB - The induction kinetics of the heat shock proteins hsp68, hsp70 and hsp84 were studied. Studies on hsp mRNA levels and protein synthetic rates, with or without the presence of actinomycin D, showed that regulation took place at the transcriptional level. Hsp mRNA induction was followed by a transient state of unresponsiveness. At the time point where the induced hsp mRNAs were decreasing again, hsp68, hsp70 and hsp84 mRNA could not be induced by a second, identical, heat shock. Hsp68 mRNA could be induced again 12-16 h after the first heat shock. Apparently, this state really seems to be a state of reduced sensitivity, since a higher heat dose could partially overcome this unresponsiveness. PMID- 8433023 TI - Temperature-dependency of the expression of heat shock proteins in rat hepatoma cells with a different degree of heat sensitivity. AB - Of two rat hepatoma cell lines, Reuber H35 and HTC, with a different degree of differentiation and heat sensitivity, treated at 41-44 degrees C for various periods of time, the expression of thermotolerance, recovery of protein synthesis and rate of hsp synthesis were studied in relation to heat-induced cell killing. The temperature dependency of the induction of thermotolerance, either chronic or acute, was different between the cell lines; tolerance of H35 cells being induced at lower temperature than that of HTC cells. Induction of thermotolerance was related to survival decrement and the correlation was similar for both cell lines. Protein syntheses of H35 and HTC cells are equally sensitive for incubation at increased temperature, but recovery of protein synthesis after heat treatment was slightly different between the cell lines; H35 being more delayed than HTC. A strong but different correlation between total amount of protein synthesized after heat treatment and cell survival was found for the two cell lines. The increased heat sensitivity of H35 cells parallels the increased capacity of selective hsp synthesis as compared with that of HTC cells. PMID- 8433024 TI - Combination preoperative radiation and endocavitary hyperthermia for rectal cancer: long-term results of 44 patients. AB - Long-term results of 122 patients with advanced rectal cancer who were randomly treated with three different methods from July 1984 to July 1986. Of 122 patients, 44 were treated with endocavitary 915 MHz microwave applicators combined with 10 MeV X-ray or 60CO followed by surgery (group A), 38 with preoperative radiation (group B) and 40 with surgery (group C) as a control group. The temperature on the surface of the applicator touching the middle of the caudad to cephaladic extent of disease was 45-50 degrees C for 45 min twice a week for 6-8 sessions. Radiation dose was 30 Gy or 40 Gy/4 weeks. Of cases with stages 0 and A, 45.5% (20/44) were in group A, 23.7% (9/38) in group B and 12.5% (5/40) in group C (chi 2 test p < 0.05 and p < 0.01, respectively). Five-year survival rate was 66.7% (24/36) in group A, 50% (14/28) in group B and 40.5% (15/37) in group C. Percentage of survival at 5 years was 73.7% (14/19) for 40 Gy plus heat, 57.1% (8/14) for 40 Gy alone, 58.8% (10/17) for 30 Gy plus heat, and 42.9% (6/14) for 30 Gy alone. Data suggest a survival advantage for patients treated with preoperative radiation combined with endocavitary hyperthermia. PMID- 8433025 TI - Modelling aperture antennas in the near- and far-field regions using subarrays of equivalent uniformly illuminated apertures. AB - This paper develops and presents an application of Huygen's principle herein referred to as the equivalent uniformly illuminated aperture method (EUAM). This method is used to predict the E-field patterns of aperture antennas in both the near- and far-field regions. In applying this method the radiating aperture is mathematically replaced by an array of smaller, uniformly illuminated aperture sources. Thus the true aperture field is approximated in a step-wise manner by the individual sub-apertures that are uniformly illuminated by the field at the point on the aperture where the sub-aperture is located. This method is suitable for analysing any antenna if its aperture fields are known. Comparisons are made between this method, an equivalent dipole method, and experimental measurements. These calculations and measurements show that the EUAM is more accurate (especially in the near-field region), is much simpler to implement, and requires less execution time than the equivalent dipole method. PMID- 8433026 TI - Inductive heating of ferrimagnetic particles and magnetic fluids: physical evaluation of their potential for hyperthermia. AB - The potential of colloidal subdomain ferrite particle suspensions (SDP) ('magnetic fluids'), exposed to an alternating magnetic field, is evaluated for hyperthermia. Power absorption measurements of different magnetic fluids are presented in comparison to multidomain ferrite particles (MDP). Variations with frequency as well as magnetic field strength have been investigated. The experimental results clearly indicate a definite superiority of even non optimized magnetic fluids over MDP ferrites regarding their specific absorption rate (SAR). Based on the work of Shliomis et al. (1990) and Hanson (1991), a solid-state physical model is applied to explain the specific properties of magnetic fluids with respect to a possible use in hyperthermia. The experimentally determined SAR data on magnetic fluids are used to estimate the heating capabilities of a magnetic induction heating technique assuming typical human dimensions and tissue parameters. It is considered that for a moderate concentration of 5 mg ferrite per gram tumour (i.e. 0.5% w/w) and clinically acceptable magnetic fields, intratumoral power absorption is comparable to RF heating with local applicators and superior to regional RF heating (by comparison with clinical SAR measurements from regional and local hyperthermia treatments). Owing to the high particle density per volume, inductive heating by magnetic fluids can improve temperature distributions in critical regions. Furthermore, localized application of magnetic fluids in a tumour might be easier and less traumatic than interstitial implantation techniques. PMID- 8433027 TI - Effects of hyperthermia on bone. I. Heating rate patterns induced by microwave irradiation in bone and muscle phantoms. AB - We describe the initial heating rate patterns generated by microwave irradiation of 915 MHz, with constant power output, in muscle-equivalent phantoms containing a freshly excised bone, and compared with those in phantoms consisting of muscle equivalent gel only. At 1 cm depth the muscle was cooler in the centre of the field when bone was present underneath. Also, the orientation of the bone in the field had a pronounced effect on the heating rate profiles in the overlying muscle: when the long axis of the bone was parallel to E field, a hot area in the centre of the field was observed; after rotation of the applicator by 90 degrees so that the long axis of the bone was perpendicular to the E field, more homogeneous heating was obtained along most of the field. In contrast, the heating patterns obtained in the cortex of the bone at similar depth (1.3 cm) were not substantially influenced by its orientation in the field. Depending on field location, the heating rate of the cortical bone closest to the applicator was within 50-75% of the SAR in muscle at the same depth. We believe that these data may be useful for the extension of such measurements in vivo, to permit the effective application of hyperthermia, with or without radiation, in the treatment of bone lesions. PMID- 8433028 TI - Effects of hyperthermia on bone. II. Heating of bone in vivo and stimulation of bone growth. AB - Previous studies in vitro have shown that it is possible to achieve comparable temperature distribution in bone and the adjacent soft tissues, under appropriate experimental conditions. The objective of the present work was to determine the effects of hyperthermia on bone in vivo. In order to obtain direct temperature measurements in bone, catheters were surgically installed on top of and inside the medullary cavity of the femur of normal rabbits. The thighs were irradiated with 915 MHz microwaves for 45 min, once or twice a week. The temperatures on and inside the bone were maintained between 42.5 and 44.0 degrees C; the resulting temperatures in the muscle were within 1.0 degrees C at depths equidistant from the applicator. After four to six treatments the femora were excised for histopathological examination. New trabecular bone was deposited around the catheters; most bone components including periosteum, osteoid, and fully calcified matrix could be seen. Large numbers of osteoblasts and osteoclasts lined the trabecular surfaces, and numerous cement lines were visible, running in all directions, indicating extensive bone deposition and remodelling. In contrast, control bones (catheters installed--no hyperthermia) showed much less ossification, with many areas of thin incomplete osteoid. Further, bones treated with hyperthermia only (no surgical trauma) showed no such changes. Thus, it appears that following an initial insult, hyperthermia promotes bone deposition. PMID- 8433029 TI - Association of HSP72 with the nuclear (TX-100-insoluble) fraction upon heating tolerant and non-tolerant HeLa S3 cells. AB - HSP72 levels in the cellular and the nuclear (TX-insoluble) fraction before and after heating of heat- and sodium arsenite-induced thermotolerant and non tolerant HeLa S3 cells have been investigated by 1D- and 2D-electrophoresis, followed by Western blotting and immunostaining, using a newly developed monoclonal antibody that specifically detects HSP72 (Heine et al. 1991). HSP72 was constitutively expressed in HeLa S3 cells and elevated upon heat or arsenite stress. Immediate association of HSP72 with the nuclear fraction was induced by heat but not arsenite. However, at the time of maximal thermotolerance, elevated levels of HSP72 were found associated with nuclei isolated from both heat- and arsenite-induced thermotolerant cells. After (test) heat treatments (0-60 min at 45 degrees C) translocation of HSP72 to the nuclear fraction in all cells was observed, albeit with different kinetics and to different plateau values. When tolerant and non-tolerant cells were allowed to recover from a heat stress (at 37 degrees C) before isolation of the nuclei, no dissociation of HSP72 from the nuclear fraction was observed within a 5 h time period. Our data indicate that association/dissociation of HSP72 with/from the nuclear fraction is not related to the recovery from heat-induced intranuclear protein aggregation (Kampinga et al. 1992), nor to the extent of thermotolerance in the human HeLa S3 cell line. PMID- 8433030 TI - Predictive value of intracellular ATP level for cell viability after heating in malignant cells. AB - An adenosine triphosphate (ATP) assay is known to be a useful chemosensitivity test, which correctly reflects cell viability. We investigated the usefulness of ATP assay as a thermosensitivity test by comparing two world-wide accepted assays which included a succinate dehydrogenase (SD) assay and a colony assay. We exposed KSE-1 and KSE-2 cell lines to various degrees of hyperthermia at 42, 43 and 44 degrees C for 0.5, 1, 2, 3 and 4 h, respectively. The ATP activity for the KSE-1 and KSE-2 cell lines was 2.0 and 0.7% in change of cell viability after heating at 44 degrees C for 4 h, respectively. Colony formation rates in the KSE 1 and KSE-2 cell lines were 0.9 and 0%, respectively, whereas the SD activity of each cell line was 24.1 and 22.8%. As a whole, the ATP assay showed a closer correlation to the colony assay than the SD assay because the latter revealed a more than 20% pseudo-viability due to the response between the base and residual enzyme even after the cells had died. Thus, the ATP assay was judged to be more sensitive than the SD assay; it was also quicker than the colony assay in evaluating cell viability after heating. We propose that the ATP assay should be included as another useful thermosensitivity test for malignant cells. PMID- 8433031 TI - Cytokine networks and the pathogenesis of glomerulonephritis. PMID- 8433032 TI - Holocrine secretion of calprotectin: a neutrophil-mediated defense against Candida albicans? PMID- 8433033 TI - Mechanisms of drug-induced lung disease. PMID- 8433034 TI - Glycine and cytopreservation: disappointments and promises. PMID- 8433035 TI - Sulfated polysaccharides in inflammation. PMID- 8433036 TI - Biocompatibility: the need for a systems approach. PMID- 8433037 TI - Clusterin: an enigmatic protein recruited by diverse stimuli. PMID- 8433038 TI - Serum concentration and localization in tumor cells of proteasomes in patients with hematologic malignancy and their pathophysiologic significance. AB - The pathophysiologic significance of proteasomes in hematologic malignancies was examined by comparison of the proteasome levels in normal subjects and patients with benign liver diseases. The serum proteasome level measured by enzyme-linked immunosorbent assay was found to be positively correlated with the tumor burden of the patients with hematologic malignancies such as acute leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, and myeloma. Immunohistochemical staining showed that proteasomes were strongly expressed in these tumor cells, especially in the nuclei. These data suggest that the elevated levels of serum proteasomes in these patients are derived from tumor cells, reflect the tumor burden, and so provide prognostic information. However, in patients with benign liver diseases, serum proteasome levels correlated with serum alanine aminotransferase activities, suggesting that in hematologic malignancies associated with liver injury some of the serum proteasomes may originate from hepatocytes. The marked production of proteasomes by malignant blood cells may be involved in transformation and proliferation of these cells. PMID- 8433039 TI - Inhibition of pseudohyphal growth as a neutrophil-mediated host defense mechanism against experimental deep Candida albicans infections in mice. AB - Neutrophils have recently been found to have microbistatic activity in addition to their well-described microbicidal mechanisms; therefore, a murine model of deep candidiasis was used to evaluate the possibility that both antimicrobial activities might participate in the host defense against this type of infection. In nonleukopenic animals, subcutaneous injection of Candida albicans yeast cells produced local abscesses and early metastatic spread of the infection to the kidneys. Although completely isolated within a dense neutrophilic infiltrate, a significant proportion of the fungal cells in the subcutaneous abscesses of these animals remained viable for at least 6 to 10 days after inoculation; the infections at this site were observed to resolve after spontaneous rupture of the abscesses. Growth of the organisms appeared to be suppressed at later time points in these animals, as evidenced by the markedly reduced proportions of multicelled pseudohyphae (representing organisms that had undergone cell division) observed in their abscess exudates as compared with those in samples from leukopenic animals. In addition, at 10 days after inoculation, very few multicelled pseudohyphae were observed histologically in the subcutaneous infections of nonleukopenic animals, whereas masses of these forms were found in leukopenic ones. Fluids from the abscesses of the nonleukopenic animals appeared to contain growth-inhibiting activity for C. albicans, in that the organisms could not grow in them unless additional zinc were to be added to the medium. This type of zinc reversibility is a characteristic of neutrophil microbistatic activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433040 TI - Infusion of glycine does not attenuate in vivo ischemic acute renal failure in the rat. AB - Recent in vitro studies have demonstrated that the amino acid glycine affords profound protection against hypoxic injury in isolated rat proximal tubules and the isolated perfused rat kidney. In the present study we have examined the in vivo effect of glycine in a rat model of ischemic acute renal failure. Acute renal failure was induced in rats by right uninephrectomy and clamping of the left renal artery for 45 or 60 minutes. Glycine infusion was initiated 60 minutes before renal artery clamping at a rate to increase serum glycine levels above 2.0 mmol/L. Control rats received a 5% dextrose infusion. In the control rats, both 45 minutes and 60 minutes of clamping resulted in reversible acute renal failure and a serum creatinine level after 24 hours averaging 2.1 +/- 0.3 mg/dl (mean +/- SEM) and 3.3 +/- 0.4 mg/dl, respectively. Glycine treatment did not attenuate the decrease of renal function in the 45-minute and 60-minute models, with serum creatinine averaging 2.1 +/- 0.4 mg/dl and 3.4 +/- 0.5 mg/dl, respectively. Histologic examination also did not reveal any differences between control and glycine-treated rats. Therefore, we conclude that infusion of glycine does not afford in vivo protection against acute ischemic renal injury in the rat. The in vitro protective effects of glycine therefore cannot be extrapolated to the in vivo situation. PMID- 8433041 TI - Biocompatibility of hemodialysis membranes: evaluation in an ovine model. AB - We studied the cardiopulmonary, hematologic, and inflammatory response to hemodialysis with seven different membranes in sheep. We also compared acetate dialysate with bicarbonate dialysate and evaluated the role of thromboxane in mediating these responses to dialysis with Cuprophan membranes (Baxter Healthcare Corp., Renal Division, Deerfield, Ill.) in sheep. The data generated in these studies indicate that dialyzer membranes can be divided into three major categories, defined by propensity to activate complement. High complement activators such as Cuprophan (low surface-area CF-1511 and high surface-area ST 25 dialyzers) produced dramatic neutropenia and hypoxemia and significant (p < 0.01) increases in the plasma concentration of thromboxane and in mean pulmonary artery blood pressure. The magnitude of these effects appeared to be surface area related. The low-flux Fresenius F-6 polysulfone membrane (Fresenius USA Inc., Concord, Calif.) also resulted in the generation of significant levels of C3a. In contrast, low complement activators such as polyacrylonitrile (AN-69; Gambro Hospal, Inc., Lakewood, Colo.) and cellulose triacetate (CT-110G; Baxter) produced little or no neutropenia, small transient increases in thromboxane, and no rise in mean pulmonary artery pressure. Dialyzers with intermediate complement activating potential such as cellulose acetate (CA-110; Baxter) and Hemophan (HT 100; Baxter) produced small to moderate degrees of neutropenia and small increases in thromboxane and mean pulmonary artery pressure. Treatment of sheep with sodium ibuprofen before dialysis with Cuprophan CF-1511 membranes prevented the initial increases in mean pulmonary arterial pressure and thromboxane generation and the decrease in arterial oxygen tension, but did not affect the degree of complement activation or neutropenia. In sheep undergoing Cuprophan dialysis, bicarbonate dialysate did not prevent the increase in circulating complement and the associated neutropenia otherwise seen during the early portions of dialysis with acetate dialysate. Bicarbonate dialysate did, however, reduce (not prevent) the initial increases in thromboxane and mean pulmonary arterial pressure, and the magnitude of the hypoxemia seen with the use of acetate dialysate. The results of these experiments therefore indicate that (1) reactions in sheep correlate well with data collected in human beings and the model can be an effective means for comparing novel dialysis membranes and pharmacologic interventions during dialysis and (2) although complement appears to be the transducer of the hematologic and immunologic response, thromboxane appears to be the final effector of the cardiovascular responses to hemodialysis with Cuprophan membranes. PMID- 8433042 TI - Left ventricular myocardial blood flow, metabolism, and effects of treatment with enalapril: further insights into the mechanisms of canine experimental pacing induced heart failure. AB - Left ventricular myocardial blood flow and metabolic parameters were studied in dogs with severe heart failure induced by rapid ventricular pacing. The impact of early administration of enalapril was also evaluated. Seventeen dogs were randomly assigned in a blinded fashion to receive enalapril at a dose of 10 mg orally per day or a matching placebo commencing 1 week after initiation of pacing. Six dogs underwent sham operations and served as a control for the myocardial blood flow and metabolic studies. In general, there was no significant difference in myocardial blood flow among the control dogs, the placebo-treated, and the enalapril-treated, paced dogs. However, tissue adenosine triphosphate was markedly reduced in both the enalapril-treated, paced dogs (2.43 +/- 0.55 mumol/gm wet weight, mean +/- SD) and the placebo-treated, paced dogs (2.79 +/- 0.39 mumol/gm) compared with the level in control dogs (4.77 +/- 0.88 mumol/gm, both p < 0.01). Tissue glycogen and lactate levels were similar in the three groups. The time to development of severe heart failure tended to be longer in the enalapril-treated dogs (33 +/- 12 days) than in the placebo-treated dogs (24 +/- 10 days, p = 0.07). In pacing-induced heart failure, therefore, an imbalance between energy supply and demand may contribute to the left ventricular dysfunction, myocardial ischemia does not play a major role, and early treatment with enalapril may prolong the time to development of severe heart failure. PMID- 8433043 TI - Use of metabolic inhibitors to study H2 consumption by human feces: evidence for a pathway other than methanogenesis and sulfate reduction. AB - Human fecal bacteria produce and consume hydrogen, and consumption rate is a critical determinant of the volume of H2 liberated into the colonic lumen. Two bacterial reactions that have been reported to be major consumers of H2 are methanogenesis and sulfate reduction. To determine the importance of each of these reactions, we measured the disappearance of exogenous H2 during incubation with human fecal homogenates treated with 20 mmol/L 2-bromoethanesulphonic acid (BES), an inhibitor of methanogenesis, and/or 20 mmol/L sodium molybdate (Mo), an inhibitor of sulfate reduction. Four methanogenic and four nonmethanogenic samples consumed an average of 99% and 85%, respectively, of the initial H2 during 22 hours of incubation. With methanogenic homogenates, 36% of the H2 consumption persisted despite inhibition of methanogenesis. Inhibition of sulfate reduction had no effect on the rate of H2 consumption by these eight fecal specimens. The importance of fecal sulfate availability was determined in fecal samples obtained from an additional 14 randomly selected volunteers. Incubation after supplementation with 20 mmol/L sulfate was associated with an increase in sulfide production in four of the samples, and three of these four samples also demonstrated an increased rate of H2 consumption. No such evidence of sulfate reduction was observed in the other 10 homogenates. We conclude that a bacterial reaction other than methanogenesis and sulfate reduction, perhaps the recently described reduction of CO2 to acetate, represents a major metabolic route of H2 disposal in nonmethanogenic feces and a minor, but appreciable, pathway in methanogenic feces. PMID- 8433044 TI - Agonist-induced activation of phospholipase D in bovine pulmonary artery endothelial cells: regulation by protein kinase C and calcium. AB - Regulation of phospholipase D (PLD) activity was investigated in cultured monolayers of bovine pulmonary artery endothelial cells (BPAECs). Agonists such as bradykinin, histamine, vasopressin, alpha-thrombin, and adenosine triphosphate (ATP) stimulated up to 15-fold accumulation of phosphatidylethanol (PEt) in the presence of ethanol through PLD-catalyzed phosphatidyltransferase activity. To examine mechanisms of PLD regulation, we investigated the role of protein kinase C (PKC) and Ca2+ fluxes in agonist-induced PLD activation. The PKC activator 12-O tetradecanoylphorbol-13-acetate (TPA, 100 nmol/L) produced up to a 25-fold increase in PEt formation in a time- and dose-dependent manner. PEt production was also stimulated by other cell-permeant PKC activators such as 1,2 dioctanoylglycerol and 1-oleyl-2-acetylglycerol, whereas inactive phorbol derivatives 4-alpha-phorbol-12,13-didecanoate and 4-beta-phorbol showed no effect. The effect of TPA on PEt accumulation was inhibited by the PKC inhibitors staurosporine (5 mumol/L, 95% inhibition) and sphingosine (10 mumol/L, 50% inhibition). TPA-induced PEt accumulation was almost completely abolished (> 95% inhibition) by PKC down-regulation accomplished by long-term treatment with 100 nmol/L TPA. In contrast, bradykinin- or ATP-induced phosphorus 32-labeled PA and [32P]-labeled PEt formation was only partially blocked (70% inhibition) by either staurosporine (10 mumol/L) or PKC down-regulation, suggesting that part of agonist-stimulated PLD activity may occur in the absence of PKC activation. An increase in Cai2+ appears to be involved in agonist-induced PLD activation as bradykinin-, ATP-, or Ca2+ ionophore-induced [32P]. PEt production was attenuated by either depletion of extra-cellular Ca2+ with EGTA or chelation of intracellular Ca2+ by BAPTA. TPA-mediated PEt accumulation was not affected by EGTA treatment, whereas BAPTA reduced TPA-mediated PEt formation by 50%. These results suggest that direct PKC activation is a potent stimulus for PLD activity and that the major pathway for agonist-induced PLD activation involves PKC activation and is dependent on an increase in intracellular Ca2+. Further, these studies suggest that agonist-induced PLD activation may also involve a PKC independent mechanism. PMID- 8433045 TI - Comparison of glomerular injury in juvenile versus mature rats in a remnant kidney model. AB - Glomerular compensatory hypertrophy and hypertension (HT) are two factors that have been implicated in the progression of renal disease after nephron loss. Because glomerular compensatory hypertrophy is different in young and mature animals, we studied the effects of 5/6 nephrectomy (RK) in juvenile (5 to 7 weeks of age) and mature (15 to 16 weeks) male Wistar-Kyoto rats to separate the effects of HT from normal growth and glomerular compensatory hypertrophy. The kidneys were perfusion fixed, glomerular pathology was documented, and glomerular diameter and capillary dimensions were determined by standard morphometry. Both groups developed comparable degrees of proteinuria and elevated serum creatinine level when compared with the sham operated controls (SHAM). Although the Wistar Kyoto rat is "resistant" to the development of HT, 18 of 30 juvenile RK and 3 of 12 mature RK rats developed systolic HT (> or = 150 mm Hg). Acute glomerular necrosis was seen only in the HT rats (9 of 18 juvenile and 2 of 3 mature), whereas glomerular sclerosis was seen in both HT (18 of 18 juvenile and 3 of 3 mature) and normotensive rats (4 of 9 juvenile and 3 of 9 mature). Glomerular diameter was greater in the SHAM mature than SHAM juvenile rats (165 +/- 7 microns vs 142 +/- 12 microns, p < 0.05), but the proportional increase in glomerular diameter after RK was comparable in the juvenile (20%) and mature (19%) RK rats. Increased capillary volume resulting from normal glomerular growth (compare SHAM juvenile with SHAM mature) was due to increased glomerular capillary length (LCP).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433046 TI - Laying clinical ethics open. PMID- 8433047 TI - The priesthood of bioethics and the return of casuistry. AB - Several recent attempts to develop models of moral reasoning have attempted to use some form of casuistry as a way to resolve the moral controversies of clinical ethics. One of the best known models of casuistry is that of Jonsen and Toulmin who attempt to transpose a particular model of casuistry, that of Roman Catholic confessional practice, to contemporary moral disputes. This attempt is flawed in that it fails to understand both the history of the model it seeks to transpose and the morally pluralistic context of secular, postmodern society. The practice of casuistry which Jonsen and Toulmin wish to revive is a practice set in the context of a community with a shared set of moral values and structures of moral authority. Without a set of common moral values and rankings, and a moral authority to interpret cases the casuistry of the postmodern age will be pluralistic, that is, there will be many casuistries not just one. PMID- 8433048 TI - Is care a virtue for health care professionals? AB - Care is widely thought to be a role virtue for health care professionals (HCPs). It is thought that in their professional capacity, HCPs should not only take care of their patients, but should also care for their patients. I argue against this thesis. First I show that the character trait of care causes serious problems both for caring HCPs and for cared-for patients. Then I show that benevolence plus caring action causes fewer and less serious problems. My surprising conclusion is that care is a vice rather than a virtue for HCPs. In their professional capacity HCPs should not care for their patients. Instead HCPs should be benevolent and act in a caring manner toward their patients. PMID- 8433049 TI - Clinical ethics and happiness. AB - Most contemporary accounts of clinical ethics do not explain why clinicians should be ethical. Those few that do attempt an explanation usually claim that clinicians should be ethical because ethical behavior provides an important good for the patient--better care. Both these approaches ignore the customary traditional reason for being ethical, namely, the good of the moral agent. This good was commonly called 'happiness'. The following article shows how the personal happiness of the moral agent provided a major reason for being ethical in the ancient philosophical and biblical traditions and how it continues to play a role in the more modern rights-based, Kantian and utilitarian theories. This history suggests that the personal happiness of the clinician, rightly understood, is a legitimate and important goal of clinical ethics. PMID- 8433050 TI - Voices and time: the venture of clinical ethics. AB - Four prominent views of the nature and methods of clinical ethics (especially in consultation forums) are reviewed; each is then submitted to a criticism intended to show both weaknesses and strengths. It is argued that clinical ethics needs to be responsive to the specific complexities of clinical situations. For this, the need for an expanded notion of practical reason within unique situations is emphasized, one whose aim is to facilitate decision-making on the part of those directly responsible for them and consonant with their own respective moral frameworks and conceptions of what is most worthwhile. PMID- 8433051 TI - The concept of medically indicated treatment. AB - The following article examines critically Robert Veatch's argument that respect for patient autonomy invalidates the concept of medically indicated treatment. I contend that when judgments of medically indicated treatment are distinguished from what ought to be done in a given case, all things considered, they are compatible with patient autonomy. Yet there remains a significant danger, which needs to be guarded against, that physicians will use these judgments to dominate their interactions with patients. Medicine would be impoverished, however, if physicians were barred from using clinical judgment to recommend medically indicated treatment. PMID- 8433052 TI - Regression of ECG signs of myocardial infarction related to infarct size and left ventricular function. AB - Quantitative and qualitative analyses of Q waves and QRS scores were performed on 69 patients during the early phase of first myocardial infarction (MI) and 6 months subsequently. The regression of ECG signs of MI were compared with the enzymatically estimated size of MI, the location of MI, and with the changes of global ejection fraction (GEF) assessed by radionuclide ventriculography. Among 57 patients with Q wave MI a complete disappearance of ECG signs of MI was found in 9 (15.7%). Patients with MI of inferior location showed a significantly higher reduction of Q waves (p < 0.001) and QRS scores (p < 0.001) than the anterior MI group. In the group of 12 patients with non Q wave MI, 11 demonstrated complete regression of MI signs. Among all Q wave and non Q wave MIs, the authors found no significant difference in the size of MI between patients with and without complete regression of ECG signs of MI. The median of the percent of change of the QRS score was significantly higher (p = 0.04) in the group of patients with improved GEFs than in the group of patients with decreased or unchanged GEFs 6 months following acute MI. The sensitivity, specificity, and predictive values for improved left ventricular function according to the change of Q waves and ECG scores were 91%, 32%, and 62%; for changes of Q waves, 81%, 40%, and 63%; and for changes of ECG scores, 91%, 36%, and 64%, respectively. In the group of patients with non Q wave MI these values were 100%, 50%, and 91% as a result of ST-T disappearance. PMID- 8433053 TI - Correlation between various parameters derived from body surface maps and ejection fraction in patients with anterior myocardial infarction. AB - To determine the best map parameter to predict cardiac function, various map parameters were correlated with the left ventricular ejection fraction (EF) in patients with a previous (between 3 months and 1 year) anterior myocardial infarction, but without overt congestive heart failure or ventricular dyssynergy. From 300 consecutive patients with a previous myocardial infarction, 82 patients with only an anterior infarction and who underwent cardiac catheterization and body surface mapping were selected for this study. The maps from 100 healthy subjects were used as normal controls. Body surface maps using 87 unipolar electrodes were recorded and various parameters were derived from the Q map, the QRS departure maps, the QRS isointegral (IQRS) map, and the QRST isointegral (IQRST) maps. They were compared with the angiographically determined EF. The EF was correlated with nQ (r = -0.72), four parameters derived from the QRS departure map (r ranged from -0.73 to -0.79), two parameters derived from the IQRS map (r = -0.90 and -0.86), and two parameters derived from the IQRST map (r = -0.84 and -0.85). Some parameters derived from body surface maps were found to have a very high correlation with the EF in patients who had a previous anterior myocardial infarction. PMID- 8433054 TI - ECG body surface potential mapping many years after successful surgery for coarctation of the aorta. AB - Patients with coarctation of the aorta (CoA) who previously underwent successful surgery are often diagnosed on standard electrocardiograms as having partial right bundle branch block. After surgery 24 patients with CoA had body surface potential mapping (BSPM) with the Case Western Reserve University 180 electrode system; of these 7 had additional aortic stenosis and none had ever had intracardiac communication. The average age at the initial surgery for CoA was 4.0 +/- 3.3 years and at the time of the BSPM it was 12.7 +/- 5.9 years. For the 17 patients with CoA without aortic stenosis the average age at the initial surgery was 5.0 +/- 3.4 years and at the time of the BSPM it was 14.2 +/- 6.0 years. In 11 of the 24 patients, a cardiac catheterization was performed, and each patient demonstrated normal pulmonary artery and right ventricular systolic pressure except for one child with 40 mmHg systolic. In the others all indications were that right ventricular pressure was normal. In 11 of the 24 patients, congestive heart failure had been present in infancy. All 24 cases had evidence for epicardial right ventricular breakthrough on the BSPM, a finding believed to indicate right ventricular activation from endocardium to epicardium via the normal Purkinje system. There were no findings on the BSPM suggesting that right bundle branch block was present. Right ventricular hypertrophy with or without terminal right conduction delay was present on the BSPM in 19 of the 24 patients (9 with additional left ventricular hypertrophy--left ventricular hypertrophy alone in 5). Right ventricular hypertrophy could be considered in 6 of 19 patients in the electrocardiogram, and in 11 of 19 in the vectorcardiogram. The mechanism for the persistent electrocardiographic right ventricular hypertrophy is postulated to involve right ventricular hyperplasia in utero or in early neonatal life, which never disappears. PMID- 8433055 TI - Body surface potential mapping of ST-segment shift in patients undergoing percutaneous transluminal coronary angioplasty. Correlations with the ECG and vectorcardiogram. AB - The purpose of this study was to investigate the thoracic patterns of ST-segment shift induced by the occlusion of different coronary arteries during percutaneous transluminal coronary angioplasty. Body surface potential maps were recorded with 63 leads during sinus rhythm before, during, and after balloon inflation in 20 patients. Two patients underwent dilatation of both the right and circumflex coronary arteries. A 12-lead scalar electrocardiogram and a Frank vectorcardiogram with orthogonal leads X, Y, and Z were obtained with the body surface potential maps. The body surface potential maps at 40 ms during the ST segment showed patterns that were specific to the dilated vessel. The left anterior descending coronary artery (n = 10) was associated with the largest ST segment shifts with a precordial maximum and negative potentials over the back; for the right coronary artery (n = 7), negative potentials covered the upper left torso with a left mid-axillary minimum and positive potentials over the rest of the torso; for the left circumflex coronary artery (n = 5), negative potentials covered the anterior torso with a precordial minimum and positive potentials over the back. These changes dissipated rapidly after balloon deflation. ST levels measured on orthogonal leads showed values greater than standard electrocardiographic leads for circumflex and right coronary arteries. In conclusion, body surface potential mapping provides a comprehensive approach for the evaluation of electrocardiographic changes and the development of optimal leads for the detection of acute occlusion of a coronary artery. PMID- 8433056 TI - Automated interpretation of cardiac arrhythmias. Design and evaluation of a computerized model. AB - Historically, the development of computerized models that utilize the deductive methods used by clinicians for the interpretation of cardiac arrhythmias have been limited by the absence of a consistently reliable means of detecting atrial activation. In this study, a theoretical model was developed with a hierarchical organization of problem-solving strategies utilizing automated analysis of atrial activation from a commercially available esophageal pill electrode and ventricular activation from a simultaneously recorded surface electrocardiographic lead. The theoretical model was then tested in 21 patients with 1 or more of 28 distinct supraventricular and ventricular arrhythmias. Of the 641 individual cardiac cycles analyzed, 636 (99.2%) were correctly identified. The accuracy of a contextual, that is, more comprehensive, interpretation of consecutive cardiac cycles was 638/641 (99.5%). The following cardiac arrhythmias were identified: sinus rhythm, sinus bradycardia, atrial premature depolarizations, atrial flutter, and supraventricular tachycardias with normal and aberrant ventricular conduction, first-degree and second-degree heart block; junctional escape, junctional rhythm, idioventricular rhythm, ventricular premature depolarization, and ventricular tachycardia with and without retrograde activation; atrial bigeminy, atrial trigeminy, atrial couplets, ventricular bigeminy, ventricular trigeminy, and ventricular couplets. This study represents the first computerized model ever developed to incorporate the morphology and timing of atrial activation with the morphology and timing of ventricular activation for arrhythmia diagnosis. Such modeling appears to be capable of achieving accurate interpretation of spontaneous, complex clinical cardiac arrhythmias and atrioventricular relationships. PMID- 8433057 TI - The "giant R waves" ECG pattern of hyperacute phase of myocardial infarction. A case report. AB - The author describes a rarely appreciated electrocardiographic (ECG) pattern of the hyperacute phase of myocardial infarction, characterized by the transient development of very tall R waves merging with maximally elevated ST-segments, and the reduction of the depth, or complete disappearance of S waves. Similar ECG findings are frequently recorded in epicardial and precordial tracings in the animal laboratory, immediately following experimental occlusion of a coronary artery. In patients with acute myocardial infarction, the "giant R waves" ECG pattern is seen very early in the clinical course. Often the ECG appearances described above are missed either because patients suffering a myocardial infarction do not present to the hospital shortly after the inception of symptoms, or are attributed to conduction abnormalities of the classic variety or to ventricular tachycardia. The incidence of the giant R waves ECG pattern in the setting of clinical acute myocardial infarction is not known. Also its pathophysiologic, clinical, and prognostic correlates remain to be defined by appropriately designed research protocols. PMID- 8433058 TI - Atrioventricular junctional and orthodromic atrioventricular reentrant tachycardia in Wolff-Parkinson-White syndrome. AB - The existence of two or more types of reentrant tachycardias in the same patient with Wolff-Parkinson-White syndrome has been emphasized, and the occurrence of orthodromic atrioventricular (AV) reentrant tachycardia and AV junctional reentrant tachycardia have been well documented. This report describes a patient with Wolff-Parkinson-White syndrome in whom the phenomena of spontaneous transition from AV reentry to AV junctional reentry and adenosine-induced conversion from AV junctional reentry to AV reentry were observed. PMID- 8433059 TI - The presence of small q waves and decreased precordial r waves indicates a small amount of fibrosis of the anterior myocardial wall. AB - Biopsy specimens were obtained from the anterior wall of the left ventricle during aortocoronary bypass surgery in 79 patients with critical narrowing or occlusion of the left anterior descending artery. The percent of fibrous replacement on histological analysis was calculated using the point-count method and compared with electrocardiographic findings in the precordial leads. In specimens from 19 patients with abnormal Q waves, the percent of fibrosis ranged between 38% and 100% (mean, 61 +/- 17%). Fifteen patients had small q waves or decreased r waves, and the percent of fibrosis in these patients ranged between 20% and 45% (mean, 38 +/- 10%). Specimens from 45 patients with normal QRS complexes had between 3% and 27% (mean, 11 +/- 5%) fibrosis of the entire thickness of the anterior wall. Thus, small q waves or decreased r wave amplitude in the precordial leads indicates a lesser degree of myocardial loss than the presence of abnormal Q waves. PMID- 8433060 TI - Acute pulmonary embolism as the cause of global T wave inversion and QT prolongation. A case report. AB - A 57-year-old man without prior history of organic heart disease was admitted with a diagnosis of unstable angina because of chest pain and new electrocardiographic (ECG) changes of global T wave inversion and QT interval prolongation. Left and right heart catheterization with coronary angiography, pulmonary angiography, ventilation-perfusion scintigraphy, and echocardiography showed absence of coronary artery disease but unequivocally acute pulmonary embolism. Within days following anticoagulant therapy, the lengthened QT interval became normalized while the global T wave inversion persisted. A follow-up ECG 15 months later revealed complete resolution of the T wave inversion. The possible pathophysiologic mechanism of the ECG changes is discussed. PMID- 8433061 TI - The temporal organization of behavior on periodic food schedules. AB - Various theories of temporal control and schedule induction imply that periodic schedules temporally modulate an organism's motivational states within interreinforcement intervals. This speculation has been fueled by frequently observed multimodal activity distributions created by averaging across interreinforcement intervals. We tested this hypothesis by manipulating the cost associated with schedule-induced activities and the availability of other activities to determine the degree to which (a) the temporal distributions of activities within the interreinforcement interval are fixed or can be temporally displaced, (b) rats can reallocate activities across different interreinforcement intervals, and (c) noninduced activities can substitute for schedule-induced activities. Obtained multimodal activity distributions created by averaging across interreinforcement intervals were not representative of the transitions occurring within individual intervals, so the averaged multimodal distributions should not be assumed to represent changes in the subject's motivational states within the interval. Rather, the multimodal distributions often result from averaging across interreinforcement intervals in which only a single activity occurs. A direct influence of the periodic schedule on the motivational states implies that drinking and running should occur at different periods within the interval, but in three experiments the starting times of drinking and running within interreinforcement intervals were equal. Thus, the sequential pattern of drinking and running on periodic schedules does not result from temporal modulation of motivational states within interreinforcement intervals. PMID- 8433062 TI - Auditory successive conditional discrimination and auditory stimulus equivalence classes. AB - This paper describes an experimental demonstration of stimulus equivalence classes consisting entirely of auditory stimuli. Stimuli were digitized arbitrary syllables (e.g., "cug," "vek") presented via microcomputer. Training and testing were conducted with a two-choice auditory successive conditional discrimination procedure. On each trial, auditory samples and comparisons were presented successively. As each comparison was presented, a response location (a rectangle) appeared on the computer screen. After all stimuli for a trial were presented, subjects selected one of the response locations. Six subjects acquired the conditional discrimination baseline, 4 subjects demonstrated the formation of three-member auditory equivalence classes resulting from sample-S+ relations, and 1 subject demonstrated equivalence classes resulting from sample-S- relations. Four subjects received additional training and subsequently demonstrated expansion of the three-member classes to four members each. PMID- 8433063 TI - Molar versus local reinforcement probability as determinants of stimulus value. AB - During one component of a multiple schedule, pigeons were trained on a discrete trial concurrent variable-interval variable-interval schedule in which one alternative had a high scheduled rate of reinforcement and the other a low scheduled rate of reinforcement. When the choice proportion between the alternatives matched their respective relative reinforcement frequencies, the obtained probabilities of reinforcement (reinforcer per peck) were approximately equal. In alternate components of the multiple schedule, a single response alternative was presented with an intermediate scheduled rate of reinforcement. During probe trials, each alternative of the concurrent schedule was paired with the constant alternative. The stimulus correlated with the high reinforcement rate was preferred over that with the intermediate rate, whereas the stimulus correlated with the intermediate rate of reinforcement was preferred over that correlated with the low rate of reinforcement. Preference on probe tests was thus determined by the scheduled rate of reinforcement. Other subjects were presented all three alternatives individually, but with a distribution of trial frequency and reinforcement probability similar to that produced by the choice patterns of the original subjects. Here, preferences on probe tests were determined by the obtained probabilities of reinforcement. Comparison of the two sets of results indicates that the availability of a choice alternative, even when not responded to, affects the preference for that alternative. The results imply that models of choice that invoke only obtained probability of reinforcement as the controlling variable (e.g., melioration) are inadequate. PMID- 8433064 TI - Verbal self-reports about matching to sample: effects of the number of elements in a compound sample stimulus. AB - Adults' self-reports about their choices in a delayed matching-to-sample task were studied as a function of the number of elements (one, two, or three) in a compound sample stimulus. Signal-detection analyses were used to examine control of self-reports by the number of sample elements, by the speed and accuracy of choices reported about, and by several events contingent on self-reports. On each matching-to-sample trial, a sample element appeared as one of two comparison stimuli. Choice of the matching element, if made within 500 ms of the onset of the comparison stimuli, produced points worth money or chances in a drawing for money, depending on the subject. After each choice, subjects pressed either a "yes" or "no" button to answer a computer-generated query about whether the choice met the point contingency. The number of sample elements in the matching to-sample task varied across trials, and events contingent on self-reports varied across experimental conditions. In Experiment 1, the conditions were defined by different combinations of feedback messages and point consequences contingent on self-reports, but self-reports were systematically influenced only by the sample stimulus manipulation. Self-report errors increased with the number of sample elements. False alarms (inaccurate reports of success) were far more common than misses (inaccurate reports of failure), and false alarms were especially likely after choices that were correct but too slow to meet the point contingency. Sensitivity (A') of self-reports decreases as the number of sample elements increased. In addition, self-reports were more sensitive to choice accuracy than to choice speed. All subjects showed a pronounced bias (B'H) for reporting successful responses, although the bias was reduced as the number of sample elements increased and successful choices became less frequent. Experiment 2 demonstrated that the failure of point contingencies to influence self-reports in the first experiment was not due to a general ineffectiveness of the point consequences. Rates of inaccurate self-reports decreased when they resulted in point losses and increased when they resulted in point gains. PMID- 8433065 TI - Tests for control by exclusion and negative stimulus relations of arbitrary matching to sample in a "symmetry-emergent" chimpanzee. AB - In the present experiments, controlling relations in arbitrary matching-to-sample performance were tested in a 9-year-old female chimpanzee who showed statistically significant emergence of symmetry in previous two-choice conditional discrimination experiments. In Experiment 1, a novel (undefined) sample stimulus was followed by a pair of trained (defined) and undefined comparison stimuli to assess the control by exclusion in arbitrary matching. The chimpanzee selected the undefined shape comparison, excluding the defined one, in color-sample-to-shape-comparison probe trials, although stimulus preferences were relatively stronger than control by exclusion in shape-sample trials. An additional test for control by relations of the sample to the positive comparison (S+ control) showed that her behavior was also under the control of relations of the sample to the positive comparison. In Experiment 2, a defined sample was followed by a pair of negatively defined and undefined comparisons to test control by the relations of the sample to the negative comparison. (S- control). The subject selected undefined comparisons in both color-shape and shape-color test trials. These results clearly indicate that the conditional discrimination behavior of this "symmetry-emergent" chimpanzee was under both S+ and S- control. Furthermore, her performance was also under control by exclusion in color-shape arbitrary matching, unlike other chimpanzees who showed no evidence of symmetry but only S+ control of arbitrary matching. PMID- 8433066 TI - Determinants of human performance on concurrent schedules. AB - Six experiments, each with 5 human adults, were conducted to investigate the determinants of human performance on multiple concurrent variable-interval schedules. A two-key procedure was employed in which subjects' key presses produced points exchangeable for money. Variables manipulated across experiments were (a) changeover delay (Experiments 2, 4, and 6), (b) ordinal cues related to scheduled reinforcement frequencies (Experiments 3 and 4), and (c) instructions describing the ordinal relations between schedule-correlated stimuli and scheduled reinforcement frequency (Experiments 5 and 6). The performances of only 13 of the 30 subjects could be described by the generalized matching equation and were within a range of values typical of those reported in the animal literature. Eight subjects showed indifference, 9 undermatched, 7 approximated matching, 3 overmatched, and a further 3 responded exclusively to the richer component of the concurrent schedules. These differing modes of responding were closely related to the different types of performance rules reported by subjects in postexperimental questionnaires. The results are in good agreement with those from studies of human performance on single schedules, suggesting that rule-governed behavior, in interaction with contingencies, may be an important determinant of human choice. PMID- 8433067 TI - Assessing control by elements of complex stimuli in delayed matching to sample. AB - A series of six experiments examined delayed identity matching-to-sample performances of subjects with mental retardation. The stimuli were either one or two simultaneously displayed forms. When the reinforcement contingencies required that only one form exert discriminative control, all subjects achieved high accuracy scores. However, accuracy scores were substantially lower when the contingencies required discriminative control by two forms, suggesting restricted stimulus control. The decline in matching accuracy appeared to reflect selective losses of conditional control by sample stimuli and shifts in control to features of the comparison stimulus displays. The experiments suggest improved techniques for assessing control by complex stimuli and for evaluating the effects of procedures that seek to broaden restricted stimulus control. The results challenge interpretations based on stimulus-generalization decrement or shared attention. PMID- 8433068 TI - The cytokine network. PMID- 8433069 TI - Opportunistic infections of the oesophagus in AIDS patients: clinical and therapeutic problems. AB - The gastrointestinal tract is frequently involved in the acquired immunodeficiency syndrome. One of the most common digestive manifestations is dysphagia/odynophagia which constitutes the presenting feature of the syndrome in a number of patients and occurs in many others during the subsequent phases of the illness. In the majority of cases it is due to an oesophageal infection by opportunistic pathogens (fungi or viruses or both) and may be successfully treated, at least temporarily, by specific antimicrobials. The present article examines the most recent acquisitions in terms of diagnosis and treatment of such common clinical problem. PMID- 8433070 TI - Hallucinogenic mushroom use by Danish students: pattern of consumption. AB - A survey among Danish students revealed that 33 (7.2%) of the respondents had experience with hallucinogenic mushrooms (HM). Afterwards these students answered an extended questionnaire about habits and pattern of consumption. It seems that mushroom use is experimental and may be due to risk-seeking behaviour but is mostly recreational and restricted to a few events. Age over 25 years and male sex were statistically related to a higher lifetime consumption rate of HM. The age of first time users was significantly lower for marijuana than for HM. Only 15 of the respondents wanted to continue use. Most of them were males and they had significantly more friends with HM experience than those who would not continue. We recommend that surveys of drug abuse include questions concerning HM to monitor the trends and extent of HM abuse. PMID- 8433071 TI - Moclobemide overdose. AB - Moclobemide is a recently introduced short-acting, selective and reversible monoamine oxidase inhibitor, type A, with few and mild side-effects at therapeutic doses. Fifteen reported cases of moclobemide overdose were studied in detail and are presented here. While pure mechanism overdosage seems benign, a combination with tricyclic antidepressants may result in serious poisoning even when the moclobemide overdose is modest. PMID- 8433073 TI - Day and night variation in ambulatory blood pressure in type 1 diabetes mellitus with nephropathy and autonomic neuropathy. AB - The objective was to study ambulatory blood pressure and heart rate variability between day and night in patients with type 1 (insulin-dependent) diabetes mellitus with different degrees of diabetic nephropathy, and to evaluate the influence of autonomic neuropathy and type of antihypertensive treatment. Twenty type 1 diabetic patients with diabetic nephropathy and antihypertensive treatment were studied with 24-h ambulatory blood pressure monitoring using an oscillometric method. They were compared with eight insulin-treated diabetic patients with short duration of diabetes (1-5 years) and with 10 apparently healthy subjects. The degree of autonomic neuropathy was evaluated by measuring the RR-interval during deep breathing and uprising. The 24-h blood pressure was generally higher in patients with diabetic nephropathy compared to those other two groups. These patients also had a lower ratio between day and night in diastolic blood pressure compared to the control subjects (1.15 +/- 0.12 vs. 1.25 +/- 0.76, P < 0.05) and heart rate compared to the diabetic patients without nephropathy, as well as the control subjects (1.15 +/- 0.08 vs. 1.26 +/- 0.09 vs. 1.27 +/- 0.08, P < 0.01, respectively). All patients with diabetic nephropathy had clinical signs of autonomic neuropathy as judged by RR-interval measurements during deep breathing and uprising. PMID- 8433072 TI - Elevated level of erythropoietin in congestive heart failure relationship to renal perfusion and plasma renin. AB - BACKGROUND: In animal experiments reduction of renal perfusion can stimulate erythropoietin production. The relationship between renal haemodynamics and erythropoietin production is unknown in congestive heart failure. OBJECTIVE: The aim was to study the relationship between serum erythropoietin and renal haemodynamics, plasma renin activity and haematocrit in patients with congestive heart failure and in healthy control subjects. PATIENTS AND METHODS: Serum erythropoietin, renal plasma flow, glomerular filtration rate and plasma renin activity were determined in 14 patients with acyanotic congestive heart failure, and 36 healthy controls. RESULTS: Serum erythropoietin was significantly elevated in congestive heart failure 26.6 U l-1 (median) compared with controls 17.0 U l-1 despite a normal haematocrit, and increased with the severity of congestive heart failure (New York Heart Association class II: 17 U l-1 [n = 4]; class III: 30 U l 1 [n = 5]; class IV: 45 U l-1 [n = 5]). Significant inverse correlations between serum erythropoietin and renal plasma flow (r = -0.60, P < 0.03), and between serum erythropoietin and glomerular filtration rate, were found in congestive heart failure but not in the control subjects. A significant positive correlation (r = 0.71, P < 0.03) was demonstrated between serum erythropoietin and plasma renin activity in congestive heart failure. CONCLUSION: A severe reduction in renal perfusion in congestive heart failure appears to cause an increase in serum erythropoietin. PMID- 8433074 TI - Left ventricular thrombosis and arterial embolism in acute anterior myocardial infarction. AB - To study left ventricular thrombus (LVT) formation and arterial embolism (AE), 106 consecutive patients with a first acute anterior myocardial infarction (AAMI) underwent two-dimensional echocardiography before discharge. Repeated assessments for detection of AE were performed. Patients were non-randomly allocated to either no heparin, low-dose heparin or high-dose heparin. LVT was found in 25 (26.9%) of 93 patients with technically satisfactory echocardiograms. Left ventricular (LV) wall motion impairment (P = 0.0017) and treatment with either heparin or low-dose heparin (P = 0.0019) were independent predictors of LVT formation. AE, all strokes, occurred in 10 patients (9.4%) and was strongly associated with high age (P = 0.0013). In conclusion, LVT and AE are frequent complications to AAMI. LV wall motion impairment predisposes for LVT and low-dose heparin seems not to prevent these complications. PMID- 8433075 TI - Fructose and insulin sensitivity in patients with type 2 diabetes. AB - The effect of dietary fructose (20% of carbohydrate calories, 45-65 g day-1 for 4 weeks) on glycaemic control, serum lipid, lipoprotein and apoprotein A-I and A-II concentrations and on insulin sensitivity was studied in 10 type 2 diabetic patients. The study was done in a randomized, double-blind fashion with crystalline fructose or placebo administered evenly during 4 meals or snacks per day. The patients were hospitalized throughout the study periods. The fasting plasma glucose concentration decreased during the fructose (from 10.7 +/- 1.4 mmol l-1 to 8.0 +/- 0.8 mmol l-1, P < 0.02) and the control diet (from 10.1 +/- 0.9 mmol l-1 to 8.0 +/- 0.7 mmol l-1, P < 0.05). The mean diurnal blood glucose concentration also fell both during the fructose (from 10.8 +/- 0.5 mmol l-1 to 8.4 +/- 0.3 mmol l-1, P < 0.001) and the control diet (from 10.3 +/- 0.3 mmol l-1 to 8.8 +/- 0.9 mmol l-1, P < 0.01). The HbA1 concentration improved (P < 0.02) only during the fructose diet. Insulin sensitivity increased by 34% (P < 0.05) during the fructose diet, but remained unchanged during the control period. Serum insulin, triglyceride, apoprotein A-I and A-II concentrations, body weight, blood pressure and blood lactate remained unchanged during both diets. In conclusion, substitution of moderate amounts of fructose for complex carbohydrates can improve glycaemic control and insulin sensitivity in patients with type 2 diabetes. PMID- 8433076 TI - Stroke morbidity in patients treated for hypertension--The Skaraborg Hypertension Project. AB - Stroke incidence was analysed in a Swedish cohort of male (n = 1428) and female (n = 1812) hypertensive patients in comparison with age- and sex-matched population controls (1:1) and with normotensive untreated subjects (1249 men and 1247 women). Mean follow-up was 8.3 years. Patients were aged 40-69 at the start of follow-up in 1977-1981. Relative risks (95% confidence interval [CI]) for stroke morbidity were 1.63 (1.16, 2.29) for men and 1.40 (0.94, 2.09) for women compared to population controls. Corresponding figures for stroke mortality were 1.96 (1.01-3.82) and 1.48 (0.71-3.06). Compared to the normotensive sample with adjustment for smoking and body mass index relative risks for stroke morbidity were 3.07 (1.96-4.80) for men and 2.56 (1.46-4.51) for women. The prognosis of treated hypertension with respect to stroke is better than anticipated from previous studies, a fact that should be considered when treatment guidelines are developed. PMID- 8433077 TI - Hepatic cytosolic oestrogen receptors in patients with liver disease. AB - Patients with liver disease present many of the features of 'feminized' hepatic metabolism. Oestrogens exert their effects through interaction with specific cellular high-affinity receptors (ER). We measured hepatic ER in 102 needle biopsies from patients with chronic alcoholic and non-alcoholic liver disease using an enzyme immunoassay. Fifteen patients with no or minimal changes in liver histology served as controls. The hepatic ER concentrations were significantly (P = 0.05) lower in the 44 men (median 13 fmol mg-1 protein, interquartile range 7 17 fmol mg-1 protein) compared to the 58 women (median 15 fmol mg-1 protein, interquartile range 10-21 fmol mg-1 protein). Patients with alcoholic liver disease (n = 63) had significantly (P < 0.05) lower ER concentrations than controls (n = 15) (median 13 fmol mg-1 protein, interquartile range 7-17 fmol mg 1 protein vs. median 16 fmol mg-1 protein, interquartile range 10-26 fmol mg-1 protein), and compared with patients with non-alcoholic liver disease (n = 24) (P < 0.05, median 20 fmol mg-1 protein, interquartile range 11-24 fmol mg-1 protein). ER concentrations were significantly lower (P < 0.05) in patients with alcoholic liver disease and alcoholic hepatitis (n = 21) compared to those without alcoholic hepatitis (n = 42) (medians 10 vs. 14 fmol mg-1 protein, interquartile ranges 6-15 fmol mg-1 protein vs. 9-18 fmol mg-1 protein), while ER concentrations did not differ significantly (P > 0.05) between actively drinking (median 13 fmol mg-1 protein, interquartile range 7-17 fmol mg-1 protein) and abstaining alcoholic patients (median 13 fmol mg-1 protein. interquartile range 7 18 fmol mg-1 protein). In summary, the small but significant variation in hepatic ER concentrations reflects variation in liver function rather than an effect of ethanol. PMID- 8433078 TI - Apolipoprotein E phenotypes in familial hypercholesterolaemia: importance for expression of disease and response to therapy. AB - To study the possible importance of variation at the apolipoprotein (apo) E gene locus for the clinical expression of heterozygous familial hypercholesterolaemia (FH), we determined apo E phenotype and serum lipoprotein pattern in 120 patients with FH. The allele frequency of the patients studies were: epsilon 2 0.033, epsilon 3 0.733, and epsilon 4 0.233. There was no influence of apo E phenotype on the serum concentrations of total. VLDL, LDL or HDL cholesterol, triglycerides, or of apo AI, B or (a). Serum concentrations of apo E were significantly higher in patients with the apo E 3/3 phenotype compared to those with apo E 4/3 or 4/4, and the highest concentrations were found in patients carrying the epsilon 2-allele. The cholesterol-lowering response to therapy with cholestyramine or pravastatin was not related to apo E phenotype. It is concluded that variation at the apo E gene locus is not of major importance for the expression of heterozygous FH. PMID- 8433079 TI - Serum cholesterol and high density lipoprotein cholesterol distributions in patients with acute myocardial infarction and in the general population of Kuopio province, eastern Finland. AB - As part of the FINMONICA project, serum total cholesterol (TC) and high density lipoprotein cholesterol (HDLC) concentrations were determined in 1216 AMI patients (937 men, 279 women) aged 35-64 years in the province of Kuopio in eastern Finland during the 5-year period 1983-87. The distributions were compared with the corresponding distributions in a representative sample of the general population of the same area (1026 men, 1021 women). The mean serum TC levels did not differ between the AMI patients and the normal population. Only the prevalence of a very high serum TC level (> 8.0 mmol l-1) among women was significantly higher in the AMI group than in the population sample. On the other hand, in both sexes the age-adjusted mean HDLC was significantly lower in the AMI group than in the population sample. Our findings emphasize the importance of HDLC measurement as a part of the assessment of the lipid risk factor profile in patients with AMI. PMID- 8433080 TI - The prevalence of coronary heart disease in the multi-ethnic and high diabetes prevalence population of Mauritius. AB - The prevalence of coronary heart disease (CHD) was determined in a population survey in Mauritius where the prevalence of non-insulin dependent diabetes and mortality from CHD are amongst the highest in the world. Men and women aged 35-74 years of all major ethnic groups were included: Asian Indians (Hindus and Muslims), Creoles and Chinese. ECG abnormalities suggesting either 'probable CHD' or 'possible CHD' were defined using standard criteria. The overall prevalence of probable CHD was 2.7% in men and 0.9% in women, and that of probable or possible CHD together 17.8% in men and 33.3% in women. The prevalence of CHD did not vary significantly between the four ethnic groups. In the multivariate analyses, age and high blood pressure were the most important independent predictors of ECG abnormalities. Neither diabetes nor serum insulin seemed to contribute independently to the prevalence of CHD. This survey confirmed the high ranking of Mauritius in international mortality statistics. The high rates of CHD seen in Asian Indians, African-origin Creoles and Chinese in the rapidly developing country of Mauritius may be a pointer to future problems in their regions of origin. PMID- 8433081 TI - Sixteen years of plasma exchange in a homozygote for familial hypercholesterolaemia. AB - This report describes 16 years of plasma exchange in a female familial hypercholesterolaemia homozygote. During childhood she had values for total serum cholesterol of 25-30 mmol l-1. She developed tendon and skin xanthomas before the age of 12 months. Because her total serum cholesterol level was not satisfactorily changed by lipid lowering drugs, plasma exchange was started in 1976. Since then she has had plasma exchange every 3 weeks. She has now reached the age of 42. Her pre-exchange values for serum cholesterol have been 11.1 mmol l-1 (6.79-28.8), while her post-exchange values have been 4.17 mmol l-1 (1.65 10.47). There has been a considerable regression of her xanthomas, and her xanthelasmas have disappeared. No side-effects have been observed during the 16 years of plasma exchange. PMID- 8433082 TI - The acute-phase response and associated lipoprotein abnormalities accompanying lymphoma. AB - Lipoprotein abnormalities seen in patients with inflammatory diseases are thought to develop secondary to circulating cytokines and the accompanying acute-phase response. Patient's with lymphoma may develop similar lipoprotein abnormalities but the mechanism is unclear. We report a patient with B-cell lymphoma who presented with an HDL cholesterol level of 3 mg dl-1, an ApoA level of 17.4 mg dl 1, elevated triglyceride level (272 mg dl-1) and an elevated ApoB level of 156 mg dl-1. Density gradient analysis of the patient's lipoproteins demonstrated a virtual absence of an identifiable HDL particle. Serum amyloid A and C-reactive protein were also elevated. All of the lipoprotein abnormalities resolved with chemotherapy and resolution of the acute-phase response. The acute-phase response may be associated with striking lipoprotein abnormalities in a subset of patients with lymphoma. Lymphoma should be included in the differential diagnosis of patients with hypertriglyceridaemia and low HDL cholesterol. PMID- 8433083 TI - Hypercalcaemia and elevated levels of parathyroid hormone-related protein in cutaneous squamous/basal cell carcinoma. AB - A patient with mixed squamous/basal cell carcinoma of the skin presented with hypercalcaemia and elevated serum levels of parathyroid hormone-related protein (PTH-rP). The tumour was resected, PTH-rP levels declined and the patient became normocalcaemic. This is the first case to associate squamous cell carcinoma of the skin with hypercalcaemia and significant levels of PTH-rP. PMID- 8433084 TI - Phonologic and semantic processing in reading-disabled and nondisabled males at two age levels. AB - The purpose of the following study was to replicate the confusability paradigm of Byrne and Shea (1979) by examining phonologic and semantic performances of good and poor readers. This study added an older age group and a phonological awareness task to examine other aspects of phonological processing across age. The confusability tasks included a pseudoword recognition task with only phonological information available for coding and a word recognition task with both phonetic and semantic information available for coding. Forty poor readers and 40 good readers were divided into two separate age groups (8-10 years, 14-16 years). Rhyming, semantic, control, and general errors were recorded. On the pseudoword task poor readers' rhyming versus control errors increased whereas good readers' rhyming versus control errors decreased with age. On the word task poor readers made more errors on semantic than rhyming trials while good readers made more rhyming than semantic errors. Poor readers made significantly more errors on the phonological awareness task than good readers. The combined results suggest, as did Byrne and Shea, that poor readers have a weak-functioning phonological system which they rely upon less when semantic information is available for coding. PMID- 8433085 TI - Competition of Li(I) and Mg(II) for ATP binding: a 31P NMR study. AB - We have examined the changes in the 31P NMR chemical shifts of ATP in aqueous solution, upon addition of NaCl and LiCl at ambient temperature. NaCl and LiCl cause qualitatively similar downfield changes, although the effect of LiCl is somewhat larger. For a 2:1 mixture of Na-ATP or tris-ATP and MgCl2 at 0 degrees C, separate beta-P peaks are observed for uncomplexed ATP and ATP complexed with Mg(II) at 121.6 MHz. Addition of LiCl slightly shifts the uncomplexed Na-ATP or tris-ATP peak downfield but does not measurably shift the Mg-ATP peak or change relative intensities. Thus, Li behaves more like Na than Mg in its ATP complexation behavior, making this system a poor model for competition between Li and Mg for macromolecular binding. PMID- 8433086 TI - Lactobionic and gluconic acid complexes of FeII and FeIII; control of oxidation pathways by an organ transplantation preservant. AB - Lactobionic acid, [4-beta-(galactosido)-D-gluconic acid] = LBA, is the major component of the Wisconsin organ transplantation preservant fluid and may suppress oxygen radical-induced tissue damage upon reperfusion by the control of FeII autoxidation. FeII and FeIII complexes of LBA and the related gluconic acid (GLC) have been studied herein by titrimetric, infrared, and electrochemical methods (CV; DPP). FeII(GLC) forms quickly at pH 7, but FeII(LBA) reacts in two steps, the second requiring 4 hr. The initial complex lacks coordination of the LBA carboxylate (C-1) and is bound by the "2,3,5" hydroxyl groups. The slow rearrangement forms a "1,2,3,6" chelate which FeII(LBA) shares in common with the donor set of the FeIII(LBA) complex. Titration data shows the removal of three protons from LBA through pH 5 and an additional proton from pH 6 to 9 which is indicative of the [FeIII(LBA)(OH)(H2O)]- formulation with LBA donating at the "1,2,3,6" positions. The more stable, second form of FeII(LBA) has been investigated in its oxidation mechanisms with H2O2 and O2 using selected trapping agents for HO. and ferryl intermediates. Eighty-six percent of the oxidation events of FeII(LBA)/H2O2 occurs in steps involving formation and reduction of freely diffusible HO.. These pathways are altered by the known HO. traps t butanol, dmso, ethanol, and methanol in the manner predictable for beta-oxidizing radicals (from t-butanol or dmso) and alpha-reducing radicals (from ethanol and methanol). Fourteen percent of the FeII(LBA)/H2O2 reaction occurs via FeIVO intermediates not trapped by t-butanol or dmso, but intercepted by primary and secondary alcohols. The HO. generating pathways are responsible for a competitive LBA ligand oxidation at the C-2 position via HO., formed from FeII(LBA) and H2O2 within the original reaction cage. Competitive ligand oxidation at C-2 is absent for the FeII(LBA)/O2 autoxidation, indicative of a different redox mechanism. The FeII(LBA)/O2 reaction rate is first-order in each component and is insensitive to the presence of t-butanol as an HO. trap. These observations support a ferryl intermediate in the autoxidation pathway and the absence of HO. or free H2O2 during autoxidation. Although chelation of FeII by hard ligand donors such as edta4-, Cl-, or HPO4(2-) accelerate the rate of autoxidation of FeII, chelation of carboxylate, alkoxy, and hydroxyl donors of LBA does not accelerate autoxidation. The implications of these findings, and the absence of an inner sphere coordination role of the 4-beta-(galactosido) functionality toward the action of LBA in organ preservant fluids, are discussed. PMID- 8433087 TI - Binding of lead to a metallothionein-like protein in human erythrocytes. AB - We have studied the erythrocytes from 24 workers occupationally exposed to inorganic lead, one asymptomatic lead worker showing exceptionally high exposure, and eight control subjects (blood lead 300-750, 1800, and < 100 micrograms/L, respectively). High performance protein chromatography, electrophoresis, and trace metal analysis have identified a low M.Wt., copper, and zinc-containing protein in all cases. This protein (designated protein M) bound lead on in vitro incubation with buffered lead nitrate. Purified samples of protein M were found to show characteristics consistent with metallothionein (M.Wt. approximately 6500, low pI, and greater UV absorbance at 254 nm). Amino acid analysis found a composition of 33% cysteine but no aromatic amino acids. The highly exposed subject showed endogenous lead binding to protein M, which on further purification by ion exchange was found to be associated with one particular constituent (protein M5). Protein M5 was present in much lower quantities in control subjects. These findings suggest the existence of a metallothionein-like protein in erythrocytes which binds lead, sequestering it into a nonbioavailable form and hence protects against lead toxicity. PMID- 8433088 TI - Effects of metallothionein on the observed copper distribution in cell extracts. AB - Systematic studies have been undertaken to compare the effects of cell lysis and chromatography conditions on the observed distribution of Cu amongst Cu-binding proteins in cultured cells. The variables included rate of centrifugation, presence or absence of non-ionic detergent, and presence or absence of dithiothreitol. The application of an improved FPLC gel filtration system has permitted us to examine the effects of the addition of exogenous metallothionein (MT) to cell extracts. When the cell extract contains low levels of endogenous MT, the addition of MT in the presence of dithiothreitol causes a shift of copper to the MT peak. High levels of MT can therefore remove copper from other Cu binding ligands during cell homogenization, hence producing artifactual Cu distribution results. The use of an anaerobic buffer system has greatly reduced the observed level of Cu exchange, and has allowed comparison of Cu distribution in normal cells and cells from patients with Menkes' disease. PMID- 8433089 TI - Composition and biological activity of chromium-pyridine carboxylate complexes. AB - Coordination complexes of chromium (Cr) and two pyridine carboxylate isomers, nicotinate (nic) and picolinate (pic) were synthesized and analyzed. Cr mono and dinicotinate complexes were formed with 1:1 and 1:2 ratios of Cr3+ and nic at pH 7.5. Cr dinicotinate was the only complex formed from a 1:3 ratio of Cr3+ and nic. Mono, di, and tri picolinate complexes were formed with 1:1, 1:2, and 1:3 ratios of Cr3+ and pic at pH 7.5. Cr is coordinated with nic through the carboxyl carbon while Cr is coordinated with pic through both the pyridine nitrogen and the carboxyl carbon. Cr dinicotinate enhanced insulin activity in isolated adipose tissue. None of the other complexes were active in this assay system. In contrast, Cr tripicolinate, which is lipophilic, increased glucose uptake by skeletal muscle cultures but none of the other complexes were effective. In addition, dietary supplements of Cr tripicolinate increased rate of lean body mass development in humans and decreased hemoglobin glycation in aging rats. None of the other complexes was effective in these in vivo assays. The results of this investigation prove that the chemical properties of Cr nic and Cr pic complexes differ markedly. The chemical differences result in a vast difference in the biological action of the complexes. PMID- 8433090 TI - Dinuclear complexes of platinum having anticancer properties. DNA-binding studies and biological activity of bis(4,4'-dipyrazolylmethane-N,N')- bis[dichloroplatinum(II)] and related complexes. AB - Some DNA-binding experiments employing a selected number of novel dinuclear platinum complexes with the 4,4'-dipyrazolylmethane (dpzm) ligand are reported. A DNA-cleavage assay using Eco RI and Bam HI restriction endonucleases to probe the binding of the complexes at or near their unique restriction sequences of pUC9 DNA has been examined. The complex beta-[Cl2Pt(dpzm)2PtCl2] has a greater affinity for DNA at the Eco RI restriction sequence over the Bam HI site. To our knowledge, the preferential inhibition of Eco RI activity is unprecedented for any platinum species reported to date. Further, the dinuclear complexes beta [Cl2Pt(dpzm)2PtCl2], beta-[Cl4Pt(dpzm)2PtCl4] x 0.5dmf x 0.5H2O and [Cl4Pt(dpzm)2PtCl2] are capable of inhibiting Eco RI activity to a far greater extent than the platinum anticancer drug cis-[PtCl2(NH3)2] (cisplatin). The in vivo and in vitro anticancer properties of some of the platinum complexes are also described. The complexes alpha-[Cl2Pt(dpzm)2PtCl2] x 0.5dmf and beta [Cl2Pt(dpzm)2PtCl2] display significant activity against P388 lymphocytic leukemia in mice. PMID- 8433091 TI - Positron emission tomographic (PET) studies in dementia. AB - Positron emission tomographic (PET) studies of regional cerebral glucose metabolism were performed in patients with various types of dementia, patients with Parkinson's disease but without dementia, and healthy normal controls. Patients with Alzheimer-type dementia showed significant decreases in glucose metabolism in frontal, temporal, parietal, sensory-motor and striatal regions. Patients with Pick's disease revealed decreased glucose metabolism in frontal and temporal regions. Parkinsonian patients with dementia had significant reductions of glucose metabolism in frontal, temporal, parietal, occipital, sensory-motor and striatal regions. Patients with Huntington's disease revealed decreased glucose metabolism in frontal, parietal and striatal regions. Patients with Creutzfeldt-Jakob's disease showed marked decreases in glucose metabolism throughout all brain regions. On the other hand, patients with Parkinson's disease but without dementia exhibited no reductions of cerebral glucose metabolism. Cerebral glucose hypometabolism in these various types of dementia might reflect neuronal dysfunction and cell death. PMID- 8433092 TI - Developmental studies of dystrophin-positive fibers in mdx, and DRP localization. AB - Dystrophin positive fibers (DPFs) were observed in about 1% of the total muscle fibers in 1-year-old mice. Some of these fibers were found to have positive staining with all six antibodies, while others showed a negative reaction with specific antibodies. These results suggest that the most likely mechanism giving rise to these DPFs is a second site mutation which prepares in-frame deletion. A study of the frequency of DPF during development showed single and scattered DPFs in younger mice, which gradually increased in number and began to form small groups with age. DRP was observed constantly on the neuromuscular junctions in both control and mdx muscle, and surface membrane of immature muscle fibers such as regenerating fibers in mdx and newborn muscle during 2 weeks of age in control and mdx. PMID- 8433093 TI - Selective damage of hippocampal neurons in murine cerebral malaria prevented by pentoxifylline. AB - The effect of pentoxifylline, a phosphodiesterase inhibitor, was investigated on the development of cerebral malaria in Plasmodium berghei K 173 infected C57/B16 mice. No significant differences occurred in the course of parasitemia and survival time after infection between control mice and pentoxifylline treated mice. Moreover, no differences were observed between the groups with respect to the occurrence of cerebral malaria. The only striking difference was that pentoxifylline treatment selectively prevented neuronal cell damage in the sector CA1 of the hippocampus. These findings are in contrast to previous studies, where pentoxifylline prevented cerebral malaria in P. berghei ANKA infected CBA/Ca mice, another widely used model of cerebral malaria. Obvious differences exist between these models. PMID- 8433094 TI - Functional cortical interaction patterns in visual perception and visuospatial problem solving. AB - To explore the integration of functional neuronal interactions in human higher cortical functions, we applied multivariate mathematical techniques to regional cerebral blood flow (rCBF) increases induced by mental activity. rCBF was measured using the intravenous xenon-133 clearance technique with 32 bihemispheric detectors in 84 normal volunteers at rest and during both a visuoperceptual accuracy task and a visuospatial problem solving task. Both paradigms activated rCBF in bilateral premotor, motor and postcentral regions. Bilateral prefrontal activation occurred during problem solving but not during the perceptual accuracy task. Partial correlations coefficients and factor analysis identified significant interactions between numerous cortex regions in both tasks. There were highly ordered and integrated patterns of functional interaction patterns between cortex areas subserving elementary subfunctions of complex behavior. Cortical interaction analysis by such techniques is a useful tool to describe the functional anatomy of large-scale neurocognitive networks in the intact human brain. Imaging functional interactions between active cortex areas are complementary to other experimental neurophysiologic methods to explore brain-behavior relationships in health and disease. PMID- 8433095 TI - Post-ischemic brain tissue alkalosis suppressed by U74006F. AB - We monitored chronically (for 1 week) the effect of the 21-aminosteroid U74006F, a potent lipid peroxidation inhibitor, on the pH profile of the rat brain following transient forebrain ischemia. Eight rats were treated initially with 3 mg/kg i.v. of U74006F 1 min after reperfusion. A second dose of 1.5 mg/kg i.v. was given 60 min after reperfusion. A vehicle group (n = 9) was treated in the same manner, using the same volume of the vehicle solution, 20 mM citric acid, 3 mM sodium citrate, and 8 mM NaCl. Statistically significant interaction between group and time (P = 0.003) was detected for pH. Brain pH of the vehicle treated animals were significantly higher than the U74006F treated group at 24 h (P = 0.009) and 48 h (P = 0.009) of reperfusion. Chronic post-ischemic brain tissue alkalosis at 24 h (pH 7.22 +/- 0.12) and 48 h (pH 7.25 +/- 0.11) post-ischemia, observed among the vehicle treated animals (and untreated animals), was suppressed by treatment with U74006F. These results suggest a coupling between post-ischemic brain tissue alkalosis and free radical induced lipid peroxidation. PMID- 8433096 TI - Glucose metabolism in the brain of patients with essential tremor. AB - Using positron emission tomography with [18F]fluoro-2-deoxyglucose, we determined the regional cerebral metabolic rate of glucose utilization at rest in 8 medication-free patients with essential tremor and in 10 normal subjects. Taking the metabolic values of regions of interest as ratios to the mean hemispheric metabolism, the patients showed significant glucose hypermetabolism of the medulla and thalami, but not of the cerebellar cortex. This study lends support to earlier suggestions that circuits involving the inferior olivary nuclei in the medulla and the thalmus are involved in the generation of essential tremor. PMID- 8433097 TI - Serum and CSF anti-GM1 antibodies in patients with Guillain-Barre syndrome and chronic inflammatory demyelinating polyneuropathy. AB - High titers of antibodies directed against gangliosides, especially GM1, are found in the serum of patients with a variety of polyneuropathies, including those of the inflammatory type. We assayed anti-GM1 IgG and IgM levels in the serum and cerebrospinal fluid (CSF) of 23 patients with Guillain-Barre syndrome (GBS) and 10 with chronic inflammatory demyelinating polyneuropathy (CIDP) to investigate whether this immune response may also be localized within the intrathecal compartment and correlate with clinical parameters such as time interval since disease onset, disability score, preceding infectious episodes, and GM1 therapy. When compared to the control group, anti-GM1 IgG was increased in the serum of 39% of GBS and 10% of CIDP patients, whereas anti-GM1 IgM was elevated in 17% of GBS and none of the CIDP patients. In both patient groups, however, anti-GM1 antibody levels were more frequently elevated in CSF than paired sera: they belonged to the IgG class in 48% of GBS and 50% of CIDP patients, and to the IgM class in 48% of GBS and 55% of CIDP patients. In the GBS group, anti-GM1 IgM serum levels inversely correlated with time elapsed between sample collection and onset of disease (P < 0.05), whereas serum anti-GM1 IgG levels positively correlated with the loss of functional ability (P < 0.005). Increased anti-GM1 antibodies in GBS serum were not associated with clinical or serological evidence of infectious antecedents nor with previous GM1 treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433098 TI - Abnormalities of sympathetic sudomotor function in experimental acrylamide neuropathy. AB - The possible involvement of sympathetic sudomotor function by acrylamide intoxication was investigated in the mouse, and compared with nerve conduction studies and global motor tests. Acrylamide (40 mg/kg, 3 days per week, 8 weeks) was given per os to a group of mice (A1). Their motor ability to stand on the rotarod was impaired from day 11, reaching a minimum between 46 and 60 days. The number of pilocarpine reactive sweat glands (SG), evaluated by the silicone mold technique, was similar to controls at 40 days and slightly decreased at 54 days. Another group of mice (A2), given acrylamide at a higher dose (50 mg/kg, 5 days per week, 5 weeks), showed abnormalities on the rotarod by 11 days, a progressive decrease of muscle action potential (CMAP) amplitude, and significantly decreased number of reactive SG from 15 days, with respect to controls. Comparatively, sudomotor dysfunction was milder and appeared later in time than alphamotor involvement, being noticeable only after severe poisoning. The decrease in SG response is attributable to damage by acrylamide intoxication of postganglionic sudomotor nerve fibers, which are unmyelinated sympathetic efferents. PMID- 8433099 TI - Interferon-gamma promotes proliferation of rat skeletal muscle cells in vitro and alters their AChR distribution. AB - Recombinant interferon-gamma (IFN-gamma) caused a dose-dependent increase in the proliferation of myoblasts in cultures of rat skeletal muscles as determined by bromodeoxyuridine incorporation. As a result of this proliferation the number of myotubes increased in the cultures, while the fusion index was unchanged. In myotubes exposed to IFN-gamma there was a change in the distribution of nicotinic acetylcholine receptors (nAChR) as detected by binding of FITC-conjugated alpha bungarotoxin with a significant decrease in the number of linear aggregates and an increase in diffusely distributed receptors. PMID- 8433100 TI - Disruption of sleep-wake rhythmicity and daytime sleepiness in myotonic dystrophy. AB - Ten patients with myotonic dystrophy (MyD) and excessive daytime sleepiness (EDS) were studied. Daytime sleepiness was assessed by means of a subjective alertness rating scale, multiple sleep latency tests and auditory event-related potentials. In addition, the diurnal pattern of daytime sleepiness and ultradian rhythm characteristics of nocturnal sleep were assessed. The multiple sleep latency tests and the P300 component of the auditory event-related potentials gave evidence of EDS, whereas the subjective alertness ratings did not. However, the alertness ratings showed a significantly reduced circadian periodicity as compared with controls. Consistent with this, no time-of-day effect was observed for the multiple sleep latency test outcomes. The ultradian rhythm characteristics of nocturnal sleep indicated a prolonged mean cycle duration and decreased stability of NREM/REM cycle. Moreover, the temporal structure of REM sleep showed a pattern similar to that of subjects who develop free-running rhythms when living in temporal isolation. These findings suggest that EDS in MyD reflects a complex and wide-spread malfunction of the circadian and ultradian timing system. PMID- 8433101 TI - A semiquantative rating scale for the assessment of signal hyperintensities on magnetic resonance imaging. AB - Differences in grading signal hyperintensities on magnetic resonance imaging may explain earlier reported conflicting results in studies of normal aging and dementia. We designed a new rating scale in which periventricular and white matter signal hyperintensities as well as basal ganglia and infratentorial signal hyperintensities are rated separately in a semiquantative way. In this study we compared the inter- and intra-observer agreements of this scale to the widely used rating scale of Fazekas. We confirmed the poor to reasonable intra- and inter-observer agreements of the Fazekas scale. The new scale, although more elaborate, provided good agreements with respect to the white matter, basal ganglia and infratentorial signal hyperintensities. In rating periventricular hyperintensities this scale yielded no advantage. It is concluded that this scale may be of use in studies especially focussing on deep white matter pathology on MRI, because it provides more detailed information, with good intra- and inter observer reliability. PMID- 8433102 TI - Sodium is elevated in mdx muscles: ionic interactions in dystrophic cells. AB - Recent evidence suggests that cellular sodium regulation may be abnormal in muscular dystrophy. We have measured intracellular sodium concentration (Nai) in muscles of mdx mice (a model of Duchenne muscular dystrophy) using two techniques. Nai in isolated diaphragm (measured using a microelectrode) was 13.0 +/- 0.3 mM and 23.5 +/- 0.7 mM (mean +/- SE) in the control and mdx mice respectively. Nai in gastrocnemius muscle (calculated from extra- and intracellular volumes using serum and whole-muscle sodium concentrations) was 13 +/- 3 mM and 24 +/- 2 mM (mean +/- SE) in control and mdx, respectively. We argue that this abnormality in mdx tissues could reflect a reduced flux through the Na/K ATPase, although a contribution from increased Na leak cannot be ruled out. We also discuss possible consequences of an increased Nai: for example, raised Nai may lead to defective cell volume control in Duchenne dystrophy and the mdx mouse. PMID- 8433103 TI - Dominant inherited distal spinal muscular atrophy with atrophic and hypertrophic calves. AB - The clinical, electrophysiological, radiological and morphological data of 3 members of a family with autosomal dominant distal spinal muscular atrophy (DSMA) are reported. One patient has the clinical picture of peroneal muscular atrophy with atrophic calves. His father and sister suffer from cramps and fasciculations of the calves with true neurogenic muscular hypertrophy of the calves. The electromyogram and the biopsy specimen are conclusive for motor neuron disease in this family. These findings suggest that the DSMA variant as described by D'Alessandro et al. (Arch. Neurol. (1982) 39: 657-660), concerning benign spinal muscular atrophy with hypertrophy of the calves, has to be considered as a mild manifestation of DSMA. PMID- 8433104 TI - Developmental studies of the expression of myosin heavy chain isoforms in cultured human muscle aneurally and innervated with fetal rat spinal cord. AB - To study the influence of innervation of human muscle fiber type differentiation, we performed immunohistochemical studies using three monoclonal antibodies (McAbs) to myosin heavy chain (MHC) on cultured human muscles at different developmental stages. McAbs QM 355 (McAb-1), E 35-3 (McAb-2) and SM 1-11-2 (McAb 3) bound to fiber types I, IIA, IIB and IIC, types IIA, IIB and IIC, and type I, respectively. At the mononucleated cell stage the majority was immunonegative to the three McAbs; however, a few myoblasts were immunopositive to the McAb-1. They were also weakly stained with McAb-2 but not with McAb-3. In aneurally cultured myotubes (AMs), all myotubes were stained with the McAb-1 and 92.1% of AMs were positive to the McAb-2, whereas only a few (0.9%) AMs were immunopositive to the McAb-3. In contracting muscle fibers in an innervated area (CMis), which were co cultured with fetal rat spinal cord explants, the percentage of the McAb-3 positive CMis was significantly increased (8.3%; P < 0.01) compared with that of AMs (0.9%). The double staining with the McAbs-2 and -3 clearly showed that slow MHC-positive muscle fibers without fast MHC only appeared in CMis. This is the first report of the neuronal influence on the expression of human adult slow MHC isoform derived from adult human satellite cells in vitro. PMID- 8433105 TI - Age-related changes in maturation of regenerated motor innervation. AB - The dependence of spontaneous transmitter release by regenerated nerve endings on age was studied in rat extensor digitorum longus muscle after sciatic nerve crush during the first year of life. Intracellular recordings were carried out at different times after denervation in muscles of 1.5-, 3- or 12-month-old animals. The frequency of miniature endplate potentials was detected. In order to determine the percentage of multiple innervation, nerve-evoked endplate potentials were recorded. The time course of the percentage of polyinnervated muscle cells was similar in the three groups of animals, but mepp frequency increased more slowly with increasing age. Moreover, by extrapolating the intercept of linear regression for mepp frequency vs days from denervation, a conventional initial time of reinnervation may be computed: the results are consistent with a decrease in the nerve regeneration rate during the first year of life. PMID- 8433106 TI - Vasectomy, serum assays, and coronary heart disease symptoms and risk factors. AB - We compared three serum assays (two antisperm antibody assays and one assay for circulating immune complexes) and a number of CHD-related variables in 69 vasectomized (V) and 126 non-vasectomized (NV) participants in the Portland Center for the Multiple Risk Factor Intervention Trial. Significant differences between the V and NV men were found in sperm agglutination (SA) and sperm immobilization (SI) titers, as well as in several CHD risk factors, symptoms, and treatments; men in the V group had higher titers for SA and SI, smoked more, and had lower diastolic and systolic blood pressure than men in the NV group. Differences between V and NV in SA and SI activity remained even after we controlled for any effects that CHD risk factors, symptoms, and treatments may have had on the serum assays. Antibody development tended to decrease with age-at vasectomy and increase with time-post-vasectomy. In the case of SA the antibodies clearly increased with time-post-vasectomy. PMID- 8433107 TI - Procrustean frameworks. PMID- 8433108 TI - An equilibrium model of drug utilization. AB - We propose an equilibrium model to assess the dispensing pattern of non-steroidal anti-inflammatory drugs (NSAIDs) among members of a health maintenance organization. The model incorporates observed patterns of patient switching among NSAIDs and identifies an implicit equilibrium distribution of drug dispensing, which may be used both to identify aberrations in prescription practice and to forecast the expected utilization of newly introduced drugs. NSAID dispensing patterns were stable for most quarters from 1987 to 1990. Introduction of two new NSAIDs and initiation of a pharmacy co-payment coincided with transient perturbation of the patterns. Dispensings of recently introduced NSAIDs achieved their equilibrium values in less than 2 years. PMID- 8433109 TI - The use of statistical methods in the analysis of clinical studies. AB - It is "standard" to analyze data from a clinical trial using a narrowly defined probabilistic mathematical model. This paper examines the ways in which mathematical models, in general, can be used in clinical research, the meaning of probability in the examination of clinical trials, and the philosophical flaws in the current "standard" method. An alternative formulation is proposed which is more flexible and which comes closer to meeting the needs of medical science. In this alternative formulation, significance tests are applied to the data from a study only as a first step to determine whether the data are worth further examination. After that, clinically relevant questions are answered with 50 and 95% confidence bounds. The initial significance test is tailored to be directed at a narrow class of hypotheses that, in turn, are dictated by clinical expectations. PMID- 8433110 TI - Qualitative inquiry in medical research. PMID- 8433111 TI - Do optometrists see what ophthalmologists see when they look you in the eye? PMID- 8433112 TI - Race and gender influences on the survival of patients with mouth cancer. AB - Previous studies have shown that race and gender are important correlates of survival among patients with cancer of certain sites. Since race and gender influence the stage of disease at diagnosis and the choice of therapy it has been argued that survival differentials may not be real but instead, they represent secondary associations with clinical variables. Therefore, verification of the true prognostic effects of race and gender requires proper controlling for potential confounders, such as stage and treatment. We have studied the 15-year survival experience of a hospital-based cohort of 4527 patients diagnosed with cancer of the mouth over a 28-year period in Brazil. Race and gender were strong predictors of stage and treatment. The odds ratios for no treatment were 1.35 (95% confidence limits [CL]: 1.09, 1.66) for females and 1.63 (CL: 1.29, 2.06) for non-white patients even after adjustment by stage, presumably a key criterion to define treatment. Survival differentials were found for lip cancer, with respect to race, and for cancers of the gum, floor of mouth, and other oral subsites, with respect to gender. Non-whites experienced 2.1 times the risk of lip cancer recurrence (CL: 1.20, 3.61) and 2.3 times the risk of dying from it (CL: 1.29, 4.09) as compared to whites. However, controlling for stage and treatment modality variables by proportional hazards regression reduced the same risk ratios to 1.01 (CL: 0.57, 1.78) and 1.17 (CL: 0.65, 2.13), respectively. The survival advantage experienced by females (17% lower risk of recurrences and 29% lower risk of cancer deaths) regarding other oral sites was independent from the effect of clinical factors. PMID- 8433113 TI - Hospitalizations due to poisonings in Finland. AB - Poisonings constitute an important category of causes for admission of patients to the emergency room. The annual incidence of hospitalized poisonings in Finland over 2 years (1987-1988) was 11.7 for a population of 10,000 according to the Hospital Discharge Register; it was 8.7/10,000 for drugs and 3.0/10,000 for non drugs. Children under 6 years of age were most frequently hospitalized because of poisoning (16.9/10,000), followed by adults aged 25-44 years (14.8/10,000). The leading causes of poisoning or chemical injury in children were undefined non drug poisonings; plants, berries and mushrooms mistaken for edible food, and corrosives. In patients aged 6 years or more, mainly adults, the leading causes were psychotropic drugs, ethanol, and cardiovascular drugs. The pattern of poisoning has changed markedly during the 1980s; the rate of psychotropic and sedative drug poisoning admissions have increased from 35 to 47%, and poisonings due to analgesics have also increased significantly. Conversely, poisonings caused by cardiovascular drugs and antibiotics, solvent poisonings and incidents caused by corrosives have decreased significantly (p < 0.001). PMID- 8433114 TI - Patient outcomes with co-managed post-operative care after cataract surgery. AB - This study examined the practice of co-managed post-operative care and the visual acuity outcomes and complications associated with co-managed services. Data on service utilization and medical outcomes were collected for 2822 cataract surgery procedures performed in 5 ambulatory eye centers between January and July 1988. Average age of patients was 72.8 (SD = 10.4) and 63% were female. Eighty-seven percent of eyes were co-managed. Average number of post-operative visits within 90 days was 4.7 and 6.2 for co-managed cases with and without complications, respectively. Successful visual acuity outcomes (< 20/40) were experienced by 86% of all co-managed patients. There was evidence that patients with pre-existing ocular conditions (e.g. glaucoma, macular degeneration) and serious post-surgical complications were not referred for co-management. For co-managed patients without pre-existing medical or ocular conditions, 92% had successful vision outcomes, while 77-90% with these conditions had successful outcomes. Ninety three percent of co-managed cases had no post-operative complications, and the rate of specific types of complications ranged from 0.04 to 2.0%. Using physician evaluations as the standard, sensitivity of optometrist detection of complications was 59% and specificity was 99.6%. Optometrists located in separate offices demonstrated 95.8% accuracy in assessing patients for post-operative complications. PMID- 8433115 TI - Bias due to non-differential misclassification of polytomous confounders. AB - This paper addresses potential effects of non-differential misclassification of polytomous confounders on adjusted exposure-disease associations. Although the degree of confounder-misclassification bias heavily depends on the relative distribution of the confounding variable among the compared exposure groups and the misclassification pattern, in most cases the bias is in the same direction (though to a lesser degree) than the confounding, i.e. the observed adjusted measures lie between the crude and the fully adjusted measures. In some instances, however, the confounder misclassification bias may be in the opposite direction. This is in contrast to previous understanding that non-differential confounder misclassification always tends to bias adjusted effect estimates towards the crude estimates and that the extent of this bias has a stable relationship to the degree of misclassification. Consequently, conclusions on the potential effects of non-differential misclassification of a polytomous confounder in any given study should only be made after careful sensitivity analyses which consider plausible ranges of misclassification rates. PMID- 8433116 TI - Social support, adversities and emotional distress in an Italian community sample. AB - The association of social support with emotional distress in relation to adversities such as social problems, physical health and undesirable life events was assessed in an Italian community sample of 222 men and 224 women. Univariate comparisons and logistic regression analyses showed that neither the quality of a confiding core relationship nor social support from kin confidants was related to adversities. In women only, social support from friend confidants exerted a statistically significant independent main effect together with social problems and undesirable life events in producing a greater probability of emotional distress. The implications of these findings are discussed considering the socio cultural characteristics of Italian families and individual coping strategies. PMID- 8433117 TI - Framing and labelling effects in health descriptions: quality adjusted life years for treatment of breast cancer. AB - At present there is a growing interest in the use of cost-utility analysis (CUA) to a point where it merits serious consideration by health care decision makers. However, there remain a number of theoretical and practical issues to be resolved including the way in which quality of life information is presented and described to subjects. Two potential sources of influence in the construction of the quality adjusted life year (QALY) values elicited for a recent Australian CUA of mammography screening have been investigated. 180 subjects were randomly allocated to nine different presentations of two breast cancer health descriptions to investigate the impact of some framing and labelling effects. No statistically significant differences were found in the valuations placed on these descriptions when framing and labelling effects were taken into account, either as separate framing and labelling factors or as interactions with one another. A significant difference was found in the particular values of descriptions that were written in the third person that differed in terms of whether the word "cancer" was used. The main contribution of these data is to the robustness of the health descriptions used in the cost-utility analysis of mammography screening. PMID- 8433118 TI - Likelihood ratios for continuous test results--making the clinicians' job easier or harder? AB - Clinicians' paradigms for considering diagnostic test results require decisions based on the actual test value. However, when the test result is reported on a continuous scale each possible outcome may not result in unique actions. To simplify decision making, clinicians often break down the continuous scale into dichotomous or ordered outcomes. Likelihood ratios, reported with the test outcome, help summarize the impact of diagnostic tests. Although commonly applied to dichotomous outcomes, likelihood ratios can also be applied to ordinal or continuous results. This application allows investigators to consider the effect of clinically simplifying continuous data into dichotomous or ordinal categories. The parameters of a simple logistic regression equation summarize continuous likelihood ratios, evaluate covariates, generate likelihood ratio lines, and help assess the statistical significance of more complex models. Having visually inspected likelihood ratio lines and considered statistical differences, the investigator should choose the test report format that best accounts the realities driving clinical decisions. PMID- 8433119 TI - Mortality associated with nosocomial infections: analysis of multiple cause-of death data. AB - Nosocomial infection mortality is an important problem, with estimates of magnitude placing it among the 10 leading causes of death in the United States. This is a preliminary study to determine the potential usefulness of death certificate data in providing information about the frequency of nosocomial infections and their association with other conditions listed as underlying or contributing causes of death. Multiple cause-of-death data were examined for 1988, to identify the number and characteristics of persons dying with nosocomial infections. The mortality rate associated with nosocomial infections found on death certificates was 3.83 per 100,000 person-years. This method needs to be validated by further work. Because nosocomial infections are a contributing rather than an underlying cause of death, multiple-cause mortality data may provide another way to estimate the magnitude of this problem. PMID- 8433120 TI - Patients' learning priorities for reoperative coronary artery bypass surgery. AB - This study describes the perceived learning priorities of patients undergoing reoperative coronary artery bypass surgery (CABS). The study also examines whether reoperative CABS patients' learning priorities are different from those of patients undergoing initial CABS. Data were collected by means of a 40-item questionnaire from 16 reoperative and 20 initial CABS patients during the postintensive care hospital period and again 3 months after discharge. Reoperative patients most frequently rated most items as "very important" to learn about. Few of the 40 items were rated differently by reoperative and initial CABS patients. Inhospital, reoperative patients more frequently rated "knowing who all the doctors and nurses are" as very important. After discharge, reoperative patients more frequently rated "waiting before surgery" and "sharing a room with others" as very important while less frequently rating "coping with stress" as very important. The results suggest that reoperative CABS patients rate learning as very important and that reoperative CABS patients have learning priorities similar to those of initial CABS patients. PMID- 8433121 TI - Hypertrophic cardiomyopathy: medical, surgical, and nursing management. AB - Hypertrophic cardiomyopathy (HCM) has been intriguing health care professionals for years. It is a disease of the cardiac muscle characterized by hypertrophy with or without left ventricular outflow tract obstruction. It affects people of all ages and is commonly associated with sudden death. The clinical presentation and treatment of HCM varies widely with the individual and therefore offers the cardiovascular nurse a unique challenge. This article assists the nurse in providing care to these patients by reviewing the cause and prognosis, pathophysiology, clinical manifestations, surgical and medical therapy, and the nursing care following surgical intervention for HCM. PMID- 8433122 TI - Complications of epicardial pacing wire removal. AB - Epicardial pacing wire removal (EPWR) is a procedure performed on postoperative cardiac surgery patients. Nurses who assist with or perform this procedure need to be aware of its possible complications; these include bleeding, pericardial or mediastinal tamponade, ventricular dysrhythmias, wire fragment migration, and infection secondary to retained wire fragments. Patients undergoing EPWR should be monitored for signs of complications; appropriate emergency equipment should be readily available, and nurses should educate patients on possible problems and interventions. PMID- 8433123 TI - Neurologic complications of open heart surgery. AB - Although infrequent, neurologic complications incurred following cardiac surgery represent significant morbidity. This article presents probable mechanisms of nervous system injury and discusses assessment techniques to identify the stated dysfunctions. Diagnoses for problems amenable to nursing interventions are also presented. PMID- 8433124 TI - Penetrating cardiac trauma: surgical and nursing management. AB - Penetrating cardiac injuries occur not only in military settings, but also in the civilian arena. This article focuses on the incidence, etiology, and pathophysiology of gunshot wounds and stabbing injuries. Diagnosis, treatment, and surgical approaches of penetrating cardiac injuries are presented. A clinical case study of a left ventricular stabbing injury is described and relevant nursing interventions and follow-up care addressed. PMID- 8433125 TI - Surgical intervention for tricuspid valve endocarditis: vegetectomy, valve excision, or valve replacement? AB - Illegal drug use predisposes the intravenous drug abuser to bacterial endocarditis, primarily of the tricuspid valve. The prevalence and clinical symptomatology of tricuspid valve endocarditis is reviewed, as are surgical options available to these patients. Nursing care issues that are discussed include postoperative hemodynamic monitoring, fluid resuscitation, and the psychosocial elements surrounding these patients. PMID- 8433126 TI - The pediatric cardiovascular surgery patient: a case study. AB - The pediatric cardiovascular surgery patient has many needs, based not only on the complexity of the surgical procedure, but also on anatomic, physiologic, and emotional differences. These differences have implications for nursing care in the postoperative period. This article focuses on the special needs of a child who required correction of a congenital heart defect. The specialized knowledge required by the pediatric critical care nurse to make accurate assessments of the child's status and to intervene appropriately are emphasized. Issues surrounding the care of the family of the child who experiences cardiac surgery are highlighted. PMID- 8433127 TI - Research connections. AB - Sleep pattern disturbance is a recognized phenomenon during the postoperative period of hospitalized adult cardiac surgical patients. Sleep disturbances may decrease healing and tissue repair and delay recovery. The nursing research study reviewed and critiqued in this column investigated the effect of a specific intervention (taped ocean sounds) on sleep in hospitalized postoperative coronary artery bypass graft patients. Implications for clinical practice and further research are discussed. PMID- 8433128 TI - Analysis of object motion in the ventral part of the medial superior temporal area of the macaque visual cortex. AB - 1. The medial superior temporal area (MST) is an extrastriate area of the macaque visual cortex. Cells in MST have large receptive fields and respond to moving stimuli with directional selectivity. We previously suggested that the dorsal part of MST is mainly involved in analysis of field motion caused by movements of the animal itself, because most cells in the dorsal part preferentially responded to movements of a wide textured field rather than to movements of a small stimulus. To determine whether the remaining ventral part of MST differs in function from the dorsal part, we examined properties of cells in the ventral part in comparison with those of cells in the dorsal part, using anesthetized and paralyzed preparation. 2. Most cells in the ventral part preferably responded to movements of a small stimulus rather than to movements of a wide textured field. 3. Although the cells in the ventral part did not respond to movements of a textured field over a large window, many of them began to respond when a small stationary object was introduced in front of the moving field. The direction to which the cells responded in this stimulus configuration was opposite to the direction in which they responded to movements of an object on a stationary background. Activities of these cells thus represented the direction of relative movement of an object on a background, irrespective of whether the image of the object or the background moved on the retina. 4. We conclude that the ventral part of MST is distinctive from the dorsal part of MST and is mainly involved in the analysis of object movements in external space. PMID- 8433129 TI - Responses of trigeminal brain stem neurons and the digastric muscle to tooth-pulp stimulation in awake cats. AB - 1. Cats were prepared for chronic recording from neurons in pars oralis and pars interpolaris of the trigeminal spinal nucleus. Electrodes were implanted into canine teeth for electrical stimulation and the digastric muscle for recording electromyograms. 2. Recordings were made from the animals when they were awake and unrestrained as well as when they were lightly anesthetized. Some neurons were studied under both conditions. 3. In an awake animal, single tooth-pulp stimuli of 0.1 ms duration and < or = 1 mA intensity produced no aversive behavior. 4. The response of trigeminal brain stem neurons in the awake animal to such stimuli consisted of short (approximately 3 ms)- and long (approximately 25 ms)-latency discharges whose thresholds suggested that they were both due to inputs from fast conducting primary afferent fibers. 5. Light anesthesia reduced the number of impulses in both components and in most cases completely abolished the long-latency component evoked by low-intensity stimuli. The threshold of the short-latency component was little affected by light anesthesia. It is postulated that the short-latency component is mediated by a monosynaptic input from primary afferent fibers and the long-latency component by a polysynaptic input from these same fibers. 6. All neurons that responded to tooth-pulp stimulation had inputs from other orofacial sites both in the awake and lightly anesthetized states. After light anesthesia, these receptive fields were altered in only 3 out of 15 neurons. 7. The majority of neurons (18 out of 20) were not spontaneously active in the awake animal. Spontaneous activity in the other two was reduced by light anesthesia. 8. The threshold of the digastric reflex evoked by tooth-pulp stimulation was not altered by light anesthesia, but the size of the response was reduced. 9. The effects of changing the level of anesthesia from deep to light (i.e., without and with reflex withdrawal to squeezing a paw) on the responses to tooth-pulp stimulation were also studied. Decreasing the anesthetic depth tended to decrease the thresholds and increase the magnitude of both the short- and long latency neuronal responses and the short-latency digastric response. PMID- 8433130 TI - Premotor cortex of monkeys: set- and movement-related activity reflecting amplitude and direction of wrist movements. AB - 1. Neuronal activity was recorded from the premotor cortex (PM) of Japanese monkeys while they performed hand movements with different amplitudes and directions. On each behavioral trial, two instructions were given sequentially: 1) an amplitude instruction (large or small) and 2) a direction instruction (flexion or extension). The onset of movement was triggered by a visual signal after a delay period. 2. Among various kinds of task-related neuronal activity recorded in the PM, two types were selected for study: 1) set-related activity, sustained activity change during the delay period that followed presentation of instruction signals (IS); and 2) movement-related activity, activity change immediately before and during movement, which followed the trigger signal (TS) presentation. 3. Thirty-two of 101 set-related neurons showed activity change after presentation of the first IS (Delay 1 set-related activity), when they were instructed in either amplitude or direction, but not both. All of the set-related neurons showed activity modulation after presentation of the second IS (Delay 2 set-related activity). When neurons showed both Delay 1 and Delay 2 set-related activity, they were usually more active during Delay 2, i.e., when the monkeys had received both amplitude and directional ISs. A majority of neurons with Delay 2 set-related activity (64%) showed relation to both movement amplitude and direction. Twenty-eight percent of the neurons showed relation to either amplitude or direction, but not both. These findings seem consistent with a view that serial, rather than parallel, processes of motor programming operate in preparation of intended movements. 4. A majority of PM neurons with movement related activity (51%) showed activity change related to both the direction and amplitude of movement. Forty-two percent showed selective relation to either direction or amplitude. These findings support a view that PM contributes to the control of limb movements. 5. Histological reconstruction showed that a vast majority of PM set-related neurons were located in the dorsal aspect of the PM (PMd), medial to the arcuate spur and lateral to the superior precentral sulcus. In contrast, movement-related neurons were distributed in two distinct foci: one in the ventral aspect of the PM (PMv), immediately caudal to the genu of the arcuate sulcus and lateral to the spur of the sulcus; and the other in the PMd, overlap;ing the location of set-related neurons.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8433131 TI - Speed and direction selectivity of macaque middle temporal neurons. AB - 1. We tested quantitatively the responses of 147 middle temporal (MT) cells to light and dark bars moving at different speeds ranging over a 1,000-fold range (0.5-512 deg/s). 2. We derived the following quantities from the speed-response (SR) curves obtained for opposite directions of motion. Speed selectivity was characterized by the maximum response, optimum speed, upper cutoff speed, response to slow movement, and tuning width. Direction selectivity was characterized by the direction index (DI) averaged over speeds yielding significant responses (MDI) and by the direction index at optimal speed (PDI). 3. There was an excellent correlation between speed characteristics for light and dark bars. These correlations were stronger than the correlations between direction indexes. The strongest correlations were obtained for maximum response and upper cutoff. 4. SR curves were classified into three groups: low pass (25%), tuned (43%), and broadband (28%), leaving 4% unclassified. 5. In the majority (75%) of MT cells, there was an agreement between the typology of speed selectivity for light and dark bars. Cells were classified as tuned (33%), low pass (22%), broadband (19%), and mixed (22%), leaving 4% unclassified. In addition to differences in speed characteristics, these groups also differed in response level, direction selectivity, and distribution of preferred directions. 6. For tuned cells, there was a very tight correlation of most speed characteristics for light and dark bars. 7. Direction selectivity depended on stimulus speed in most neurons, yielding a tuned average speed-DI curve. 8. Speed characteristics, proportions of speed selectivity types, and direction selectivity indexes showed little dependence on laminar position. 9. Speed characteristics and direction selectivity indexes were not dependent on eccentricity. Proportion of speed selectivity types however, changed dramatically with eccentricity: low-pass cells dominated foveally, tuned cells parafoveally, and broadband cells peripherally. 10. There were also small eccentricity effects on the range of optimal speeds shown by tuned cells and on the speed at which direction selectivity decreases in the slow speed range. PMID- 8433132 TI - Cat hindlimb muscles exert substantial torques outside the sagittal plane. AB - 1. We studied the contributions of several hindlimb muscles to ankle torque in adult cats deeply anesthetized with pentobarbital sodium. Isometric torques were measured with a multiaxis, force-moment sensor connected to the plantar surface of the foot. 2. Individual muscle torques were provoked by using a combination of muscle nerve stimulation and selective denervations and tenotomies. Torques were represented by three orthogonal components; defined as dorsiflexion/plantarflexion, inversion/eversion (rotation about the long axis of the foot), and toe-in/toe-out (rotation about the axis of the tibia). 3. Most of the muscles tested exerted substantial torques about more than one of the orthogonal axes, each of which shared a common origin centered midway between the medial and lateral malleoli. The lateral and especially the medial head of the gastrocnemius muscle exhibited large toe-out torques and eversion torques as well as the classical plantarflexion components. 4. The torque exerted by tibialis anterior was seen to oppose that of both medial and lateral gastrocnemius in each of the three directions. The toe-in and inversion torques exerted by tibialis posterior was opposed in these directions by both peroneus brevis and peroneus longus. Flexor hallucis longus exerted approximately 10 times more plantarflexion torque than did flexor digitorum longus; therefore, these two muscles cannot be considered pure synergists. 5. The major plantarflexors and dorsiflexor of the cat ankle joint contribute substantial torques outside the sagittal plane. Their opposing torques lead to increased joint stiffness; the net effect of coactivation of these muscles causes ground reaction forces oriented so as to maintain stability during quadrupedal stance. PMID- 8433133 TI - Functional imaging of human motor cortex at high magnetic field. AB - 1. We used conventional gradient echo magnetic resonance imaging (MRI) at high field strength (4 Tesla) to functionally image the right motor cortex in six normal human subjects during the performance of a sequence of self-paced thumb to digit oppositions with the left hand (contralateral task), the right hand (ipsilateral task), and both hands (bilateral task). 2. A localized increase in activity in the lateral motor cortex was observed in all subjects during the task. The area of activation was similar in the contralateral and bilateral tasks but 20 times smaller in the ipsilateral task. The intensity of activation was 2.3 times greater in the contralateral than the ipsilateral task. PMID- 8433134 TI - Output organization of intermediate cerebellum of the monkey. AB - 1. The goal of this study was to investigate the motor organization of monkey nucleus interpositus (NI) and neighboring regions of the lateral nucleus (NL) by correlating discharge of single neurons with active movements. Neurons were surveyed during free-form movements as well as during operation of six devices that required movement about specific forelimb joints. The paradigm allowed us to test the hypothesis that discharge of individual cells relates to movements about individual joints. 2. One hundred sixty-two isolated nuclear neurons from two monkeys were studied. Eighty-three percent showed large increases in discharge (an average of 3 times resting rate for forelimb neurons) during movement of one body part, either forelimb, hindlimb, mouth/face, or eyes. 3. Anterior interpositus contains neurons related to hindlimb movement in anterior regions and neurons related to forelimb movement in posterior regions. A mouth/face related area exists in the dorsal-posterior regions and is continuous with a mouth/face area in the dorsal regions of NL. Posterior interpositus (NIP) showed no clear separation between forelimb and hindlimb neurons: forelimb neurons were encountered throughout the nucleus, and hindlimb neurons were encountered in the medial-anterior two thirds. A distinct eye movement area exists in lateral, posterior, and ventral regions of NIP. This area borders regions of NL that also contain eye movement-related neurons. 4. Forelimb interpositus neurons discharged strongly during reach and grasp; discharge rates were recorded for 41 neurons during a stereotyped reach and the average depth of modulation was 149 imp/s. Nineteen neurons that modulated during device tracking were also tested during reaching, and the depth of modulation was much greater during reaching. 5. Fifty nine forelimb neurons were tested with device tracking. Twenty-seven (46%) produced no audible modulation, regardless of the joint being exercised. The remaining 32 neurons modulated during movement on at least one device (mean depth of modulation = 84 imp/s). Comparison of discharge during use of different devices revealed no strong evidence for device-specific discharge. 6. Discharge modulations during device tracking were phasic, preceded movement, and, for a small number of cells, showed consistent parametric relations to duration, amplitude, and velocity of movement. 7. Despite a clear somatotopy within NI and NL, there is no finer mapping based on active movements about individual joints within forelimb regions. Discharge modulation depends on movements involving the whole limb. Progress in understanding the function of intermediate cerebellum depends on determining the variables required to elicit consistent and high modulation of neural discharge.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8433135 TI - Movement-related inputs to intermediate cerebellum of the monkey. AB - 1. The primary goal of this study was to characterize the information about single-joint forelimb movements supplied to intermediate cerebellar cortex by mossy fibers. Discharge of mossy fibers and Golgi cells was studied while monkeys operated six devices that required movements about specific joints. Additional control experiments in anesthetized cats and monkeys established criteria for identification of mossy fibers and Golgi cells. 2. The control experiments demonstrate that mossy fibers can be distinguished from Purkinje and Golgi cells by the waveshapes of their action potentials. Asynaptic activation from the inferior cerebellar peduncle, in combination with histological localization of recording sites in granular layer or subcortical white matter, verified that mossy fibers produce a variety of waveshapes that are characterized by brief initial phases and relatively small amplitudes. The same waveshapes were observed for the mossy fiber recordings from awake monkeys, and many identified mossy fibers had sensory properties similar to those found in the awake animals. From these combined criteria, we conclude that the recordings in the awake animals were from mossy fibers. Golgi cells, recorded exclusively in the granular layer of cerebellar cortex, were characterized by action potentials of longer duration and larger amplitude as compared with mossy fibers, and none were asynaptically activated from the inferior cerebellar peduncle. 3. Units were isolated while the monkeys made free-form and tracking movements. We studied movement-related discharge of 80 mossy fibers and 12 Golgi cells. Mossy fibers showed high modulations during use of at least one of the six manipulanda and had clear preferences for movement about a specific joint, although they often showed consistent but weaker firing during movement about a neighboring joint. Separation of movements by more than one joint produced a large reduction in discharge: shoulder units never fired well to movements of the finger, and finger units never fired well to movement of the shoulder. 4. The tracking task required maintenance of fixed limb positions (a static phase) as well as movements between these positions (a dynamic phase). Of 80 mossy fibers, 18% had purely tonic discharge patterns, 63% were phasic-tonic, and 20% were purely phasic. Discharge patterns were reciprocal (45%), bidirectional (42%), or unidirectional (13%). 5. Eighty percent of the mossy fibers exhibited tonic discharge that was significantly (P < 0.01) correlated with joint angle (r = 0.65 +/- 0.19, mean +/- SD), and about one third had phasic components that were significantly correlated with movement velocity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8433136 TI - An investigation of the coupling between respiration, mastication, and swallowing in the awake rabbit. AB - 1. The interrelationships between respiration, mastication, and swallowing were studied in awake rabbits previously prepared for the chronic recording of jaw movements and the electromyographic activity of jaw and throat muscles. These signals were recorded before, during, and after the mastication of rabbit chow, together with respiratory movements. 2. The onset of activity in the thyrohyoid muscle was used as a marker for swallowing. Measurements were made of cycle duration, and the phase relationship between the masticatory and respiratory rhythms was calculated. Deviations in masticatory and respiratory movements during swallowing were detected; the phases of the masticatory and respiratory cycles in which the deviations occurred were determined, and the intervals between the deviations and the swallowing marker were calculated. 3. Two characteristic swallowing patterns were observed that were called Interposed and Terminal swallows. Interposed swallows occurred within a masticatory sequence, while Terminal swallows ended the sequence. 4. In most rabbits, respiratory rate slowed during mastication. This brought the average frequency of the two movements closer together, and there was a weak but significant correlation between the masticatory and respiratory rates. However, respiration and mastication were not linked on a cycle-by-cycle basis, and the change in respiratory rate was found to be unrelated to masticatory rate. Further, there was no tendency for the masticatory and respiratory rhythms to adopt any particular phase relationship as swallowing was approached. Some weak and transient phase coupling of the two systems occurred after swallowing. 5. During swallowing, respiration was most often inhibited soon after the start of the inspiratory phase. Swallows within a masticatory sequence occurred most frequently during the early opening phase of the masticatory cycle, and swallows after the end of a sequence occurred with the jaw in the resting position. There was a strong tendency for the durations of the masticatory and respiratory cycles containing deviations to be longer than preceding control cycles, and the effect on respiration lasted several cycles. 6. For both Interposed and Terminal swallows, a tight temporal relationship was observed between deviations in respiration and the swallowing marker: most deviations tended to occur before swallowing. In contrast, the time of deviations in mastication relative to the swallowing marker depended on swallow type and was more variable. Finally, there was no link between the start of the pauses in the two rhythms. 7. We conclude that respiratory and masticatory processes are not strongly coupled.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8433137 TI - Improving the outcome of severe head injury with the oxygen radical scavenger polyethylene glycol-conjugated superoxide dismutase: a phase II trial. AB - Formation of the oxygen radical superoxide anion is one of the final events of several metabolic pathways in the cascade that leads to delayed neuronal death after traumatic or ischemic brain injury. In the laboratory, scavenging of the superoxide anion with native superoxide dismutase (SOD) or polyethylene glycol (PEG)-conjugated SOD (PEG-SOD) has been shown to be beneficial in several types of traumatic and ischemic injury. Accordingly, PEG-SOD was utilized in a randomized controlled Phase II trial to evaluate its safety and efficacy in severely head-injured patients with a Glasgow Coma Scale score of 8 or less. At two institutions, 104 patients were randomly assigned to receive either placebo or PEG-SOD (2000, 5000, or 10,000 U/kg) intravenously as a bolus, an average of 4 hours after injury. Prognostic factors were evenly distributed in the four groups, except for mean age which was significantly higher in the group receiving 10,000 U/kg than in the placebo group (mean age 34 years vs. 25 years). No complications attributed to the study medication were noted. The average intracranial pressure (ICP) was similar in the four groups, but the percentage of time during which ICP was above 20 mm Hg was less in the groups receiving 5000 or 10,000 U/kg of PEG-SOD. Patients in the group receiving 10,000 U/kg also required less mannitol for ICP control than the placebo group. Outcome was assessed using the Glasgow Outcome Scale at 3 and 6 months postinjury in 91 and 93 patients, respectively, by blinded observers not involved in the clinical management of the patients. At 3 months, 44% of patients in the placebo group were vegetative or had died, while only 20% of patients in the group receiving 10,000 U/kg of PEG SOD were in these outcome categories (p < 0.03, multiple logistic regression test); at 6 months, these figures were 36% and 21%, respectively (p = 0.04). Differences in outcome between the placebo group and either of the other two dosage groups were not statistically significant. It is concluded that PEG-SOD was generally well tolerated and appears promising in improving outcome after severe head injury. A larger, multicenter, Phase III trial, using a higher dose (20,000 U/kg) compared to placebo and to 10,000 U/kg of PEG-SOD is planned. PMID- 8433138 TI - The perioperative use of corticosteroids and bupivacaine in the management of lumbar disc disease. AB - The introduction of microdiscectomy to lumbar spine surgery has resulted in a significant decrease in postoperative pain and length of hospital stay. Intraoperative application of long-acting local anesthetic agents has been used for many general and neurosurgical procedures for the management of postoperative pain. In addition, many surgeons routinely use intraoperative corticosteroids during lumbar discectomy to reduce traumatic nerve root inflammation. However, the efficacy of intraoperative long-acting local anesthetic agents and corticosteroids for reduction of postoperative discomfort has not been reported for lumbar discectomy. This study evaluated 32 patients at a university-based Veterans Administration hospital undergoing lumbar microdiscectomy. All 32 patients presented with radicular symptoms and had radiographic confirmation of a herniated nucleus pulposus. These patients were divided into three groups. Group 1 (12 patients) received 160 mg intramuscular Depo-Medrol (methylprednisolone acetate) and 250 mg intravenous Solu-Medrol (methyl-prednisolone sodium succinate) at the start of the operation. A macerated fat graft soaked in 80 mg Depo-Medrol was placed over the affected nerve root following discectomy. In addition, 30 ml of 0.25% bupivacaine was infiltrated into the paraspinal musculature at skin incision and during closure. Group 2 (10 patients) received 30 ml of 0.25% bupivacaine infiltrated into the paraspinal musculature at skin incision and at closure. In this group of patients, a saline-soaked fat graft was placed over the affected nerve root. Group 3 (10 patients) acted as a control group, undergoing lumbar microdiscectomy without corticosteroids or bupivacaine. Patients receiving bupivacaine and corticosteroids (Group 1) had a statistically significantly shorter hospital stay (1.4 days) compared to the control group (4.0 days) (p = 0.0004, Mann-Whitney U-test). Patients in Group 1 required less postoperative narcotic analgesia than the other groups. Finally, a larger percentage of patients in Group 1 reported complete relief of back and radicular pain on postoperative Day 1 compared to other groups. Postoperative complications and functional outcome were not different between the groups. These results indicate that the combination of long-acting anesthetic agents and corticosteroids can reduce postoperative discomfort and subsequently the length of postoperative hospital stay. PMID- 8433139 TI - Sclerosteosis: neurosurgical experience with 14 cases. AB - Fourteen cases of sclerosteosis seen during a 14-year period have been reviewed. Sclerosteosis is a craniotubular bone modeling disorder and presents with cranial nerve palsies and raised intracranial pressure; sudden death may occur without neurosurgical intervention. Experience gained from the management of these patients suggests that bifrontal decompressive craniotomy followed by a posterior fossa decompression should be performed in all cases, preferably in the second decade of life. Cerebrospinal fluid diversion procedures to reduce elevated intracranial pressure are unsatisfactory. Patients should be followed closely since the regrowth of bone may necessitate repeated decompressive procedures. Technical problems related to the surgical management are discussed. PMID- 8433140 TI - Chronic motor cortex stimulation in patients with thalamic pain. AB - Analysis of the authors' experience over the last 10 years has indicated that excellent pain control has rarely been obtained by thalamic relay nucleus stimulation in patients with thalamic pain. In the present study, 11 patients with thalamic pain were treated by chronic stimulation of the precentral gyrus. In eight patients (73%), the stimulation system was internalized since excellent pain control was achieved during a 1-week test period of precentral gyrus stimulation. In contrast, no clear effect was noted or the original pain was even exacerbated by postcentral gyrus stimulation. The effect of precentral stimulation was unchanged in five patients (45%) for follow-up periods of more than 2 years. In the remaining three patients, the effect decreased gradually over several months. This outcome was significantly better than that obtained in an earlier series tested by the authors with thalamic relay nucleus stimulation (p < 0.05). The pain inhibition usually occurred at intensities below the threshold for production of muscle contraction (pulse duration 0.1 to 0.5 msec, intensity 3 to 8 V). When good pain inhibition was achieved, the patients reported a slight tingling or mild vibration sensation during stimulation projected in the same area of distribution as their pain. The authors discuss the possibility that, in deafferentation pain, sensory neurons below the level of deafferentation cannot exert their normal inhibitory influences toward deafferented nociceptive neurons because of the development of aberrant connections. Thus, while stimulation of the first- to third-order sensory neurons at the level of the thalamic relay nucleus or below cannot bring about good pain inhibition in patients with thalamic pain, activation of hypothetical fourth order sensory neurons through precentral stimulation may be able to inhibit deafferented nociceptive neurons within the cortex. None of the patients developed either observable or electroencephalographic seizure activity. PMID- 8433141 TI - Differentiating solitary small cysticercus granulomas and tuberculomas in patients with epilepsy. Clinical and computerized tomographic criteria. AB - It is commonly believed that differentiating solitary small cysticercus granulomas and small tuberculomas in patients with seizures is difficult without resorting to an excision biopsy. The aim of this study was to formulate clinical and computerized tomography (CT) criteria to distinguish these two entities in patients with epilepsy. Toward this end, clinical and CT data from six consecutive patients with histologically proven small solitary tuberculomas and 25 consecutive patients with histologically proven solitary cysticercus granulomas were compared. Evidence of raised intracranial tension and a progressive focal neurological deficit was seen only in patients with tuberculomas (two of six cases). All tuberculomas were greater than 20 mm in size and five of the six were irregular in outline. Only tuberculomas were associated with a midline shift on CT (four of six cases). All cysticercus granulomas were less than 20 mm in size and 24 (96%) of the 25 were regular in outline, conforming to one of two characteristic patterns. No cysticercus granuloma was associated with a midline shift. Based on the above clinical findings (evidence of raised intracranial tension and a progressive neurological deficit) and CT criteria (size, shape, and association with a midline shift), it is possible to separate these two entities in a majority of patients with seizures and with a single small lesion on CT. PMID- 8433142 TI - Brain-stem glioma growth patterns. AB - During the last decade, several authors have reported that certain brain-stem gliomas may be associated with a better prognosis than others. In this paper, retrospective correlations between the pathological findings and the magnetic resonance (MR) imaging appearance of 88 brain-stem gliomas are established. The authors propose an anatomical hypothesis that helps identify glioma growth patterns in general and that clarifies why cervicomedullary, dorsally exophytic, and focal tumors have a more favorable prognosis. According to this hypothesis, growth of benign gliomas of the brain stem is guided by secondary structures such as the pia, fiber tracts, and the ependyma, which in turn leads to stereotypical growth patterns that are clearly identified on MR images. The authors believe that this hypothesis, in conjunction with clinical data, may help establish selection criteria for the surgical treatment of specific brain-stem lesions. PMID- 8433143 TI - Conventional radiation therapy of intracranial arteriovenous malformations: long term results. AB - Conventional radiation therapy has been used in the treatment of arteriovenous malformations (AVM's) for many years, but there are limited data pertaining to specific treatment parameters, long-term results, and complications. Between 1955 and 1985, 15 patients with AVM's deemed inoperable or incompletely obliterated using surgical or endovascular techniques were treated at the University of Western Ontario. There were nine males and six females, aged 15 to 48 years (mean 29 years). Presenting symptoms included hemorrhage in nine patients, seizures in four, and focal neurological deficits in two. There were three infratentorial and 12 supratentorial AVM's, ranging in size from 1.5 to 6.5 cm. Therapy prior to irradiation consisted of incomplete surgical removal in four cases and subtotal embolization in four. One patient received 2000 cGy of irradiation, while 4000 to 5000 cGy were delivered in the remaining patients to fields ranging in size from 4 x 4 to 14 x 14 cm in 15 to 28 fractions. The 15 patients have been followed for 1 1/2 to 21 years since undergoing radiotherapy (mean 8.1 years). Angiography in 12 patients at 1 to 21 years following irradiation demonstrated no significant change in seven patients, a slight reduction in AVM size in two, near-complete obliteration in one, and complete obliteration in two. One patient with an AVM measuring 6.5 cm refused angiography but underwent magnetic resonance imaging at 5 years which showed no evidence of residual AVM. There were four hemorrhages in 122 patient-years of follow-up study, indicating a hemorrhage rate of 3.3% per year. The authors conclude that conventional irradiation is successful in obliterating AVM's in only about 20% of cases. PMID- 8433144 TI - Intracranial complications of hypervolemic therapy in patients with a delayed ischemic deficit attributed to vasospasm. AB - This investigation has revealed the frequency of various intracranial complications that may result from hypervolemic therapy for a delayed ischemic deficit following subarachnoid hemorrhage (SAH). Among 323 patients with SAH, 112 patients developed a delayed ischemic deficit, 94 of whom underwent hypervolemic therapy. Infarction due to vasospasm was found ultimately in 43 of these 94 patients. Twenty-six patients (28%) developed an intracranial complication during hypervolemic therapy: cerebral edema was aggravated in 18, and a hemorrhagic infarction developed in eight. In 13 of 18 patients with aggravation of edema, delayed ischemic deficit developed within 6 days after the SAH; at that time, a massive new infarction was found in four and edema in 10 patients. After hypervolemic therapy, the 18 patients with aggravation of edema deteriorated rapidly, and 14 of them died. In every case in which hemorrhagic infarction followed hypervolemic therapy, a new infarct was found on computerized tomography (CT) when the delayed ischemic deficit became apparent. Hemorrhagic infarction developed as the delayed ischemic deficit resolved, with one exception. In patients who sustained no complication from hypervolemia, the incidence of both massive new infarction and edema at the time when the delayed ischemic deficit was manifested was only 1%. In 44 of 68 patients who sustained no complication from hypervolemia, the delayed ischemic deficit was manifested on or after the 7th day following the SAH. This study suggests that hypervolemic therapy is contraindicated in a patient who is found to have a massive abnormality on CT at the time when a delayed ischemic deficit is manifested, especially when it occurs within 6 days after the SAH. To avoid hemorrhagic infarction, it is important to discontinue hypervolemic therapy as soon as the delayed ischemic deficit resolves. PMID- 8433145 TI - Prospective study on the prevention of cerebral vasospasm by intrathecal fibrinolytic therapy with tissue-type plasminogen activator. AB - The authors have evaluated the efficacy of postoperative intrathecal injections of tissue-type plasminogen activator (tPA) in preventing cerebral vasospasm in patients with a diffuse thick subarachnoid hemorrhage (SAH). The present study examined 105 patients who underwent direct surgery within 48 hours of SAH and whose computerized tomography (CT) findings were classified as Fisher CT Group 3. Patients showing diffuse thick subarachnoid blood clots on CT with greater than 75 Hounsfield units (HU) were included in the tPA therapy group and those with below 75 HU comprised the control group. The surgical method was the same in both groups, and both groups had cisternal drainage instituted. On the day following the operation, the tPA group was given an intrathecal injection of tPA (2 mg), and this was continued for several days until all of the cisterns exhibited low density on CT scans. Follow-up angiography showed that 26 cases (87%) in the tPA group had no vasospasm, three (10%) had moderate vasospasm, and one (3%) had severe vasospasm. All four patients showing spasm on angiography were asymptomatic, and there were no cases of delayed ischemic neurological deficits (DIND). In contrast, there were 11 cases (15%) with DIND in the control group. In the tPA group, there was one case of SAH caused by drainage catheter removal, one with a small epidural hematoma, and one with subgaleal fluid accumulation; all of these were treated conservatively with favorable results. Overall, there were no infectious complications related to cisternal drainage and intrathecal injection of tPA. These results indicate that multiple intrathecal injections of small doses of tPA are effective and safe in preventing vasospasm. On the basis of this experience, the authors conclude that injection of 2 mg of tPA daily for 5 days (a total of 10 mg) is effective in preventing the development of vasospasm. PMID- 8433146 TI - Therapeutic alternatives for vein of Galen vascular malformations. AB - From September, 1986, to March, 1990, the authors treated 28 children harboring a vein of Galen vascular malformation. Eleven (39.3%) of the patients were neonates, 13 (46.4%) were 1 to 2 years old, and four (14.3%) were more than 2 years old. Fifteen patients (53.6%) presented with severe congestive heart failure, six (21.4%) had seizures, four (14.3%) had hydrocephalus, and three (10.7%) presented with intraventricular hemorrhage. Based on the Yasargil classification of malformations, 10 lesions (35.7%) were Type I, seven (25%) were Type II, eight (28.6%) were Type III, and three (10.7%) were Type IV. In 11 patients (39.3%), a combined transfemoral, transarterial, and transvenous embolization of the vein of Galen malformation was performed. A pure transtorcular approach was utilized in eight patients (28.6%), and postembolization surgical clipping of arterial feeders was performed in two cases with intractable congestive heart failure. Complete anatomical occlusion of the galenic malformation was achieved in 13 patients (46.4%). An immediate postembolization improvement in the patient's clinical status was obtained in 23 (82.1%) of 28 patients and a good long-term clinical outcome was seen in 17 patients (60.7%). Five deaths (17.9%) occurred in this series of 28 patients; three (10.7%) were related to a transtorcular embolization and two (7.1%) to the unchanged natural history of the disease. PMID- 8433147 TI - Surgical resection of intramedullary spinal cord cavernous malformations. AB - Cavernous malformations are being increasingly well recognized throughout the central nervous system, where they compose approximately 1% of all vascular lesions and 15% of all vascular malformations. These malformations are uncommon in the spinal column and rarely found within the spinal cord. There have been only a few isolated reports of surgical resection of intramedullary spinal cord cavernous malformations. A series of six patients with intramedullary spinal cord cavernous malformations is described; all were treated by complete surgical excision, and all had a good or excellent outcome with partial or complete relief of neurological symptoms. There were no surgical complications, although transient postoperative neurological worsening was common. The clinical, radiological, and surgical features of these patients are discussed. It is concluded that intramedullary spinal cord cavernous malformations are an uncommon cause of progressive myelopathy that can be safely and effectively treated by surgical excision. PMID- 8433148 TI - Drilling the posterior wall of the petrous pyramid: a microneurosurgical anatomical study. AB - Posterior approaches to the petroclival area requiring extensive drilling of the posterior pyramidal wall have been described in the last 10 years. If hearing is to be preserved, damage to the inner-ear structures must be avoided; however, the fine points of this pyramidal drilling technique have never been reported in detail. A microneurosurgical anatomical study was undertaken in 15 cadavers to determine the relationships between bone landmarks and labyrinthine structures that could be used to give some practical drilling guidelines. Drilling of the posterior pyramidal wall is facilitated on identification of the intersection of the petrous ridge with the most anterior portion of the bone ledge covering the sigmoid sinus (petrosigmoid intersection), the bony operculum of the endolymphatic sac, and the petrous ridge. Drilling may proceed rather safely at a minimum depth of 2.5 mm in an area 0.9 cm anterior and 1 cm inferior to the petrosigmoid intersection and petrous ridge, respectively. From there, identification of the vestibular aqueduct, genu, and horizontal portion is necessary to safely open the posterior wall of the internal auditory canal. The vestibular aqueduct represents the lateral and superior limits of drilling. The bone between these areas may then be safely drilled to a depth of at least 2.5 mm. A microneurosurgical dissection of the posterior pyramidal wall conducted in cadaveric material according to these guidelines did not violate any inner-ear structures. PMID- 8433149 TI - Expression of androgen and progesterone receptors in primary human meningiomas. AB - Meningiomas are common brain tumors that show a predilection for females and become more aggressive during pregnancy and menses. The existence of gender specific hormone receptors in meningiomas has long been a matter of controversy; the recent cloning of androgen, estrogen, and progesterone receptors has facilitated their direct evaluation. The authors have demonstrated the expression of androgen and progesterone receptor messenger ribonucleic acid and protein product in nine primary human meningiomas by Northern blot analysis. Cellular localization was achieved by in situ hybridization analysis. Estrogen receptor expression was not detected. Normal adult meninges were shown to express very low levels of both androgen and progesterone receptors. PMID- 8433150 TI - Inhibitory effect of trapidil on human meningioma cell proliferation via interruption of autocrine growth stimulation. AB - In a previous study, the authors demonstrated that meningioma cells secrete platelet-derived growth factor (PDGF)-like molecules that stimulate their own growth in an autocrine manner. Based on that finding, a study was undertaken to examine the effect of trapidil, a drug known to have an antagonistic action against PDGF, on cell proliferation of human meningiomas in culture. Trapidil showed a dose-dependent inhibition of meningioma cell proliferation in the absence of any exogenous mitogenic stimulation. The maximum effect was observed at a concentration of 100 micrograms/ml, with the decrease in cell growth ranging from 16% to 54% compared to control samples. Trapidil similarly inhibited the basal deoxyribonucleic acid (DNA) synthesis assessed by [3H]-thymidine incorporation in three of seven meningiomas. While the conditioned medium generated from meningioma cells remarkably stimulated the proliferation of meningioma cells (166% to 277% of control), this effect was strikingly inhibited by the addition of trapidil. Trapidil also inhibited conditioned medium stimulated DNA synthesis, even when there was no effect on basal DNA synthesis. Furthermore, trapidil significantly inhibited the epidermal growth factor (EGF) stimulated proliferation of meningioma cells. This inhibitory effect on EGF stimulated cell proliferation was also observed in nontumorous fibroblasts, demonstrating that trapidil is not an antagonist specific to PDGF. The addition of trapidil (30 micrograms/ml) in combination with bromocriptine (1 microM) showed an additive inhibitory effect on the meningioma cell growth compared to trapidil or bromocriptine alone. The overall results suggest that trapidil exhibits an inhibitory effect on meningioma cell proliferation through blocking the mitogenic stimulation induced by autocrine or exogenous growth factors, and may be considered as a possible new approach to the medical treatment of meningiomas. PMID- 8433151 TI - Inhibition of angiogenesis and growth of human nerve-sheath tumors by AGM-1470. AB - The effectiveness of AGM-1470, a potent, fungal-derived inhibitor of angiogenesis, in suppressing the neovascularization and growth of human Schwann cell tumors was tested in six schwannomas, seven neurofibromas, and one neurofibrosarcoma. Tumor fragments from surgical specimens were implanted into the subrenal capsule of 348 nude mice (nu/nu). Seven days after implantation, the tumors were measured and vascularity was graded. The animals were then randomly assigned to one of two groups, to receive either saline (control group) or systemic AGM-1470 treatment. After 2 to 6 weeks of treatment, tumor size and degree of vascularity were recorded. In the six different schwannomas implanted into 138 mice, the average vascular grade in the control group after 2 weeks of treatment increased from 2.2 to 3.2 (+1.0), while in the AGM-1470-treated group it decreased from 2.2 to 1.7 (-0.5) (p < 0.01). In the seven different neurofibromas implanted into 158 mice, the change in the average vascular grade in control and AGM-1470-treated animals was +0.5 and -1.0, respectively (p < 0.01). In the one neurofibrosarcoma implanted into 52 mice, the change in average vascular grade in each group during the 6-week treatment period was +1.9 and 1.0, respectively (p < 0.01). Neurofibrosarcoma growth after 6 weeks of AGM-1470 treatment was only 8.5% of the growth found in the control animals (p < 0.01). This study determined that AGM-1470 is effective in inhibiting angiogenesis and the growth of human nerve-sheath tumors. PMID- 8433152 TI - Use of the excimer laser in high-flow bypass surgery of the brain. AB - The technique of laser-assisted anastomosis for high-flow bypass surgery using the excimer laser is described in 15 rabbits and in one patient. The left common carotid artery of the rabbits was excised and, with two anastomoses, connected to the right common carotid artery. An end-to-side anastomosis technique was used that obviated the temporary occlusion of the recipient artery. The end of the donor artery was connected for its full circumference with the exterior of the recipient artery and, with the aid of an excimer laser catheter (introduced via an artificial side branch of the donor artery), the wall of the recipient artery was evaporated. In two animals only, occlusion of the anastomosis sites occurred. In the remaining 13 animals both anastomosis sites were proven to be patent by inspection at different times, followed by scanning electron microscopy in six animals. In a patient with hypoperfusion of the brain caused by bilateral internal carotid artery occlusion, revascularization of the right hemisphere was obtained by placing a shunt between the proximal superficial temporal artery and the intracranial portion of the internal carotid artery, using a free transplant of the right inferior epigastric artery. The anastomosis with the internal carotid artery was created using the excimer laser-assisted technique without occlusion of the recipient artery. PMID- 8433153 TI - Histological studies of intracranial vessels in primates following transluminal angioplasty for vasospasm. AB - Percutaneous transluminal angioplasty for treatment of cerebral vasospasm was performed in primates. Chronic cerebral vasospasm was induced by placement of an autologous blood clot over the right internal carotid artery (ICA), middle cerebral artery (MCA), and anterior cerebral artery (ACA). Cerebral angiography on Day 7 showed that the diameters of the ICA, MCA, and ACA were reduced to 55.7% +/- 1.3%, 55.3% +/- 2.6%, and 59.6% +/- 1.3%, respectively, of baseline. The angioplasty was carried out with a silicone microballoon attached to a microcatheter under somatosensory evoked potential (SEP) monitoring on Day 7. The angioplasty for ICA was performed satisfactorily; however, the balloon could not be advanced to the spastic M1 or A1 portions of the cerebral artery. Following angioplasty, the diameters of the ICA, the M1 segment, and the A1 segment were 79.6% +/- 2.9% (p < 0.001), 67.6% +/- 4.3% (p < 0.05), and 61.7% +/- 2.2% (not significant), respectively, of baseline. Histological studies demonstrated that the vessels were well dilated and patent without endothelial cell damage. PMID- 8433154 TI - Experimental evaluation of bilayered human collagen as a dural substitute. AB - Many substances have been tried as possible dural substitutes, and different tissues and materials have been evaluated for use in dural repair; however, an entirely satisfactory solution still remains to be found. The authors report an experimental study involving the closure of dural defects in dogs with a new biomaterial, resorbable bilayered human placental collagen, using two types of collagen material. These include a collagen bilayered dural substitute made of oxidized type III + I collagen layer covered by a type IV oxidized collagen film (collagen dural substitute I) and a collagen bilayered dural substitute made of oxidized type III + I collagen layer covered by a type III + I collagen film (collagen dural substitute II). Macroscopic and histological examination, performed over a period of between 15 and 180 days after implantation, showed the resorption of collagen graft and formation of a neomembrane that looked like a neodura within 3 months. No infection and no cerebrospinal fluid fistulae were noticed. Nevertheless, one slight cerebromembranous adhesion was found with collagen dural substitute II. The authors suggest that human resorbable collagen biomaterial could be used as a very satisfactory dural substitute. PMID- 8433155 TI - Spontaneous temporal encephalocele. Case report. AB - The authors report a 36-year-old woman with a 23-year history of simple and complex partial seizures who was treated surgically for an anteroinferior temporal encephalocele, with resolution of the seizure disorder. This patient's presentation, findings, and response to treatment are typical of those associated with anteroinferior temporal encephalocele, and different from the clinical patterns of four other types of spontaneous temporal encephalocele. PMID- 8433156 TI - External carotid artery fistula due to microcompression of the gasserian ganglion for relief of trigeminal neuralgia. Case report. AB - Vascular complications after percutaneous injection procedures for relief of trigeminal neuralgia are varied, ranging from puncture of arterial or venous structures to carotid-cavernous fistulas. The authors present a patient in whom an external carotid artery fistula occurred after a microcompression procedure for the treatment of a left-sided trigeminal neuralgia. This is believed to be the first case of this complication secondary to a percutaneous injection procedure for relief of facial pain. PMID- 8433157 TI - Transient and repetitive rises in blood pressure synchronized with plasma catecholamine increases after head injury. Report of two cases. AB - The authors report two patients with repetitive episodes of acute transient rise in blood pressure synchronized with increases in plasma catecholamine after severe head injury. In both cases, the paroxysmal hypertension occurred suddenly on the 2nd day posttrauma, and its frequency declined gradually, disappearing with time. The pathophysiological basis of this peculiar clinical manifestation is discussed. PMID- 8433158 TI - The plated bayonet: a new instrument to facilitate surgery for intra-axial neoplasms of the spinal cord and brain stem. Technical note. AB - A new instrument for use in surgically treating intra-axial neoplasms of the spinal cord and brain stem is described. The plated bayonet allows neoplastic tissue in the spinal cord to be separated from functioning neural elements without perforating the adjacent spinal cord. In addition, the plated bayonet facilitates exposure through the very small incision necessary to remove tumors of the brain stem without damaging cranial nerves or other vital structures. PMID- 8433159 TI - Posterior fossa craniotomy for lesions of the cerebellopontine angle. Technical note. AB - A safe technique is described for performing a lateral posterior fossa craniotomy to gain access to the cerebellopontine angle. The method makes use of currently available high-speed air drills. Thus, it is possible to replace the removed bone at the conclusion of the procedure and to re-establish normal tissue planes while providing rigid protection to the posterior fossa. PMID- 8433160 TI - Intraoperative localization using an armless, frameless stereotactic wand. Technical note. AB - A technique of "frameless" stereotaxy that allows real-time intraoperative neurosurgical localization is described. The system is composed of four components: a hand-held probe containing two ultrasonic emitters, a microphone array that is rigidly affixed to the operating table in proximity to the surgical field, hardware to control and detect timing of signal production and reception, and a color graphics computer workstation with software to calculate and present the location of the probe tip on reconstructed neuroimaging studies. Unlike previously reported mechanical or sonic navigational devices, this system is adaptable to a wide array of neurosurgical instruments, allows free movement of the operating table and conventional patient draping, and has accuracy in the hostile operating room environment that rivals that of frame stereotaxy. In the operating room environment, using four pulse pairs with the wand positioned optimally, reproducibility of a point in space is +/- 0.6 mm. The wand has a broad range of orientations that maintain error at or below 1.0 mm. The mean error when measuring distances within a 1000-cu cm cube is 1.1 +/- 1.0 mm (1.0% +/- 0.7%). The ability to localize a fourth point (a target) in space is typically within 1.5 mm (using computerized tomography scans with a 1-mm slice thickness) but is dependent on several variables. This technology provides a powerful yet flexible tool in the neurosurgical operating room. PMID- 8433161 TI - Brain ischemia in head injury. PMID- 8433162 TI - Neurovascular compression for CNS abnormalities. PMID- 8433163 TI - Transnasal stereotactic biopsy. PMID- 8433164 TI - Facial reanimation. PMID- 8433165 TI - Multiloculated chronic subdural hematomas. PMID- 8433166 TI - Teaching caring to the nurse administrator. AB - Theories of caring have been espoused in nursing for more than a decade. This article focuses attention on teaching caring to nurse administrators. Management and nursing literature define philosophies and ideals that can lead to enactment of caring by nursing leaders. In this way, the environment for nursing practice can reflect caring at all levels in the organization. PMID- 8433167 TI - Demystifying organizational empowerment. AB - The definition, implementation, and integration of empowerment concepts and principles is something of an enigma in healthcare organizations. As our structures become less hierarchical and more interactive, relying on vision, knowledge, performance, and example to achieve our missions, nurse executives must know not only why empowerment is essential, but how it can be used to transform their organizations from traditional into futuristic structures and systems. PMID- 8433168 TI - Organizational empowerment through self-governed teams. An application in long term care. AB - In the previous article, Barbara Tebbitt presented a framework for demystifying organizational empowerment. The authors of this manuscript discuss the application of Tebbitt's work in their long-term care facility. PMID- 8433169 TI - The impact of case management in preventive services. AB - The success of case management in increasing the use of community-based services among a variety of chronically ill and medically fragile populations and in decreasing the frequency and length of stay of hospitalization is well documented. Less well established is its impact in preventive services and cost effectiveness, and the effect on health outcomes. The author discusses evidence of the effectiveness and cost effectiveness of case management in preventive services and other healthcare contexts. Finally, the author asks an important question, that is, what differentiates the context in which case management is effective from others? The author suggests that nurse case managers are the crucial determinant of successful case management. PMID- 8433170 TI - Decision making in case management of home healthcare clients. AB - Public health nurses face ethical decision-making dilemmas in their everyday practice, but how well are they prepared to make these decisions? This research study examined the decision-making capabilities of nurses in case management in regard to terminating and maintaining services in difficult client situations. The results showed that nurses varied in their decision-making capabilities and that their beliefs about case management were not always carried out in actual practice. PMID- 8433171 TI - "Running the vicious cycle backward" and other systems solutions to nursing problems. AB - Peter Senge's book, The Fifth Discipline: The Art and Practice of the Learning Organization, is a business bestseller. The fifth discipline refers to systems thinking, a conceptual framework for making the full pattern of complex, interrelated actions clearer and helping people see how to change them. This article summarizes selected key concepts from Senge's work and explains how nurse executives can use systems thinking to gain a deeper understanding of the forces operating in recurrent situations and identify opportunities for leverage to benefit patients, staff, and healthcare organizations. PMID- 8433172 TI - Relocation stress syndrome. A patient and staff approach. AB - Administrative articles addressing hospital mergers, renovations, and unit or departmental relocations can be found in nursing and healthcare literature. However, there is a paucity of information regarding the patients' needs, both before and after relocation, especially the integration of these needs in a comprehensive relocation plan. The authors present a successfully implemented relocation plan, highlighting the need for awareness of relocation stress syndrome. PMID- 8433173 TI - 1989 Immigration Nursing Relief Act. PMID- 8433174 TI - The Albrecht Nursing Model for Home Healthcare. Predictors of satisfaction with a self-care intervention program. AB - Satisfaction with a self-care intervention program was evaluated through this quantitative study of arthritis clients at home. The results indicate that the clients were highly satisfied with the intervention. In this era of consumer satisfaction with their care, nurse administrator's knowledge of which interventions are satisfying is important for staff development and case management in the community. PMID- 8433175 TI - Implementation of a salaried compensation program for registered nurses. AB - Compensation is a key variable in recruitment and retention of registered nurses. A 6-month trial of an exempt/salaried wage program for registered nurses, based on normative change theory, was implemented in the adult critical care division of a 491-bed community hospital. A total of 58 registered nurses participated in the trial. At the end of 6 months on salary, 94% (53) of the nurses voted to remain salaried. The staff perceived that the new wage program increased flexibility in work schedules and promoted teamwork and professional autonomy. PMID- 8433176 TI - Comparing case management styles. PMID- 8433177 TI - Nurse managers' perspectives of their work. Connection and relationship. AB - Practicing hospital nurse managers were asked what they find meaningful in the performance of their roles. Three major role perspectives that make up nurse manager identity in the workplace were identified. Additionally, listening to their stories revealed a pattern of connection and relationship. Implications for how nurse manager development is viewed and facilitated and what constitutes a supportive work environment are discussed. PMID- 8433178 TI - Optimizing the use of nursing pool resources. AB - The use of per diem staff is a popular method of meeting staffing deficiencies related to fluctuations in volume and intensity of nursing service. The authors describe the reorganization of a nursing pool. This restructuring resulted in an increase of available pool hours, a decrease in overtime and agency use, and significant savings related to orientation costs. PMID- 8433179 TI - Male nurses in obstetrics. PMID- 8433180 TI - The new era nurse executive: centerpiece characteristics. PMID- 8433182 TI - Promoting smoking cessation at the workplace. Results of a randomized controlled intervention study. AB - This paper presents results from a preliminary short-term work-site intervention study aimed at smoking cessation. The 3-month intervention included consultation for employers on the adoption of a nonsmoking policy, training for nonsmokers to provide assistance to smokers attempting to quit, and cessation classes for smokers. Eight work sites from Bloomington, Minnesota were recruited to the study and randomly assigned to an intervention or comparison condition after a baseline survey of all employees. To assess the effect of the intervention, smokers were surveyed 1 and 6 months after the intervention was completed. At the 1-month follow-up, the overall quit rate in the intervention group was 12% compared to 5% in the control group (P < .05). At the 6-month follow-up, 12% of smokers in the intervention group reported quitting, compared to 9% in the control group (P < .05). Co-worker support for quitting was higher in the intervention group compared to the comparison group. Cessation was highest overall among smokers whose co-workers frequently asked them not to smoke and among those who worked with a high proportion of nonsmokers. These results indicate that a short-term, multifaceted smoking cessation program implemented in work sites can affect smoking cessation rates as well as the work-site norms about smoking. PMID- 8433181 TI - The Back Injury Prevention Project pilot study. Assessing the effectiveness of back attack, an injury prevention program among nurses, aides, and orderlies. AB - The Back Injury Prevention Project was a pilot study of "Back Attack," an educational program designed to prevent back injuries among nurses, nurses' aides, and orderlies. The pilot tested program feasibility, developed and tested instruments, and generated preliminary data measuring program effectiveness. Fifty-five nurses, aides, and orderlies on two medical/surgical units at two Kaiser Permanente medical centers in Portland, Oregon participated in the study. Intervention group scores on the composite back pain and composite fatigue scales decreased relative to the control group, but this did not reach statistical significance. A 19% improvement in scores for quality of patient transfer was observed for the intervention group (P < .0003), while the control group did not show any significant improvement during the same time period. Results of the pilot suggest that the Back Attack program changes behavior at least in the short term. Further study will be necessary to determine if the behavior change persists and back pain and injury rates are subsequently reduced. PMID- 8433183 TI - Assessment of potential violence in the paranoid worker. AB - Violence in the workplace is sometimes a manifestation of an untreated psychiatric disorder. Paranoid personality disorder, paranoid schizophrenia, and delusional (paranoid) disorder are three psychiatric syndromes in which paranoid ideation is a prominent feature. While the vast majority of people with these conditions are not violent, paranoid workers can exhibit violent behavior as a reaction to beliefs that co-workers or supervisors are threatening or persecuting them. Three cases are described to illustrate the clinical presentation of these disorders and their management in an occupational setting. PMID- 8433184 TI - Returning to work after a unilateral hand fracture. AB - We complied a case series involving 556 employed patients who sustained unilateral hand fractures requiring open reduction and internal fixation and a modification of their normal work activities and schedules. Time from injury to limited duty averaged 5 days, with 62% of the patients returning to work 1 day after surgery. Time from injury to resuming regular duty averaged 56 days. Both sexes averaged a return to work on limited duty after 5 days, but women returned to regular duty an average 5 days later than men. Patients with workers' compensation injuries, joint fractures, multiple fractures, tendon and/or nerve disruptions, and fractures requiring metal fixation rather than periosteal sutures required longer periods on off-duty and limited-duty statuses. PMID- 8433185 TI - Polychlorinated biphenyl exposure and human disease. AB - Polychlorinated biphenyls (PCBs) continue to be of great environmental and occupational health interest. This review summarizes the major clinical findings reported in individuals incurring the greatest PCB exposure--those persons working in the manufacture or repair of electrical capacitors or transformers. The potential target organs addressed in the studies reviewed include the liver, lungs, skin, cardiovascular system, nervous system, certain endocrine systems, the blood/immune system, and the gastrointestinal and urinary tracts. After careful analysis, the weight of evidence suggests the only adverse health effects attributable to high, occupational PCB exposures are dermal. This review confirms and extends the observations of others, ie, that the collective occupational experience with PCB fluids provides no evidence for adverse PCB effects on any other organ systems. PMID- 8433186 TI - Diesel asthma. Reactive airways disease following overexposure to locomotive exhaust. AB - While some of the gaseous and particulate components of diesel exhaust can cause pulmonary irritation and bronchial hyperreactivity, diesel exhaust exposure has not been shown to cause asthma. Three railroad workers developed asthma following excessive exposure to locomotive emissions while riding immediately behind the lead engines of caboose-less trains. Asthma diagnosis was based on symptoms, pulmonary function tests, and measurement of airways hyperreactivity to methacholine or exercise. One individual's peak expiratory flow rates fell in a work-related pattern when riding immediately behind the lead diesel engine. None had a previous history of asthma or other respiratory disease and none were current smokers. All three developed persistent asthma. In two cases, physiologic abnormalities suggesting reversible restriction were observed. This is the first report implicating diesel exhaust as a cause of reactive airways disease. PMID- 8433187 TI - Patients with suspected solvent-induced encephalopathy examined with cerebral computed tomography. AB - The aim of this study was to investigate the relationship between organic solvent exposure and brain atrophy among 85 patients referred to a department of occupational medicine and who underwent cerebral computed tomography. On average, the patients had been heavily exposed to a mixture of organic solvents for 22.9 years. Diseases which may be associated with brain atrophy or high alcohol consumption was observed among 31% of the subjects. Among these subjects the prevalence of brain atrophy was 58%. The prevalence of brain atrophy was 20% among the men without such conditions. None of the eight female patients appeared to have atrophy. The quantitative assessment showed no correlation between the duration of exposure and atrophy-related parameters. However, the width of the third ventricle, bifrontal ratio, and bicaudate ratio were correlated with age. PMID- 8433188 TI - Occupational exposures and diseases among medical inpatients. Prevalence, association, and recognition. AB - The purpose of this study was to identify the prevalence of occupational exposures, their potential contribution to the development of chronic diseases among medical inpatients, and their recognition by house officers. Occupational histories were obtained from 101 medical inpatients and their charts were reviewed. Sixty-six percent of patients had diseases for which an occupational etiology merited consideration. A relevant occupational exposure was discovered in 68% of patients with a disease potentially attributable to occupation. Specific disease/exposure pairs were associated with each other (P = .001). Senior house staff recognized fewer relevant exposures (17%) than did interns (55%) (P < .001). Relevant occupational exposures are common among medical inpatients, but frequently go unrecognized because of an inadequate fund of knowledge in occupational medicine among physicians. PMID- 8433189 TI - Silicon and silicone: comment on occupational medicine forum's answer on trichloroethane and connective tissue disorders. PMID- 8433190 TI - Mate de coca equals cocaine. PMID- 8433191 TI - Possible chromate-associated urticaria. PMID- 8433192 TI - CMA epidemiology guidelines. PMID- 8433193 TI - Functional outcome following surgical excision of heterotopic ossification in patients with traumatic brain injury. AB - Increased osteogenesis, both in fracture healing and heterotopically, occurs in a significant percentage of patients with traumatic brain injury. Periarticular heterotopic ossification, especially in the hip and elbow joint, can cause functional loss of motion in patients with traumatic brain injury and interfere with activities of daily living. Seventeen patients with traumatic brain injury had periarticular heterotopic ossification resected in 20 joints (13 hips and seven elbows). Each joint was ankylosed prior to surgical resection (Brooker IV). In the immediate postoperative period, the average arc of motion was 85 degrees in the hips and 65 degrees in the elbows. At the final follow-up observation (average, 23 months), 17 of the 20 heterotopic ossification resected joints had maintained functional range of motion. Three joints in two patients reankylosed. Two additional patients had significant complications. In summary, surgical excision of periarticular heterotopic ossification in patients with traumatic brain injury can give satisfactory results, provided appropriate preoperative selection is done. PMID- 8433194 TI - Limb fracture pattern in different pediatric age groups: a study of 3,350 children. AB - The fracture patterns of 3,350 children with 3,413 limb fractures admitted to one center from 1986 to 1990 were analyzed retrospectively. The overall boy-to-girl ratio was 2.7:1, rising to 5.5:1 in the adolescent group. Distal radius fracture was the most common fracture (19.87%), followed by supracondylar fracture of the humerus (16.64%) and forearm shaft fracture (13.36%). Specific age group breakdown showed that supracondylar fracture of the humerus was the most common fracture occurring in the age groups 0 to 3 years and 4 to 7 years, accounting for 28.94 and 31.18% of all limb fractures, respectively. Fracture of the distal radius occurred in 27.06% of the 8 to 11 year age group and 23.31% of the 12 to 16 year group. Open fractures were uncommon (2.17%), and greenstick fractures were found only in 5.27% of this hospital series. The nondominant arm was found to have more fractures although the number was not statistically significant. Seasonal variation in incidence occurred, with more cases in the summer and autumn months. The open reduction rate in the treatment varied from 10.15% in the 0 to 3 year age group to 33.95% in the 12 to 16 year group. Forty-five percent of the 0 to 3 year age group were discharged from hospital within 24 h, contrasting with 30% in the other age groups. Overall incidence of fractures requiring hospital treatment was estimated to range from 35 per 10,000 in the 0 to 3 year age group to 62, 60, and 57 per 10,000 in the 4 to 7, 8 to 11, and 12 to 16 year groups, respectively. PMID- 8433195 TI - Unrecognized posterior dislocation of the hip associated with transverse and T type fractures of the acetabulum. AB - Five patients who had displaced transverse or T-type fractures of the acetabulum and who were transferred 3-5 days after their injury with an unrecognized posterior dislocation of the hip are reported. On the anteroposterior pelvis radiograph, central displacement of the acetabular fragment dominated the radiographic appearance; however, superior displacement of the femoral head with superimposition on the intact acetabular roof was a consistent finding. The typical radiographic findings of adduction and internal rotation of the femur were not present. Oblique views of the pelvis, and/or a computed tomography scan made the diagnosis obvious. Appropriate initial radiographic evaluation is imperative in all patients with acetabular fractures. Failure to recognize the posterior hip dislocation in this group of patients may have led to an increased incidence of avascular necrosis of the femoral head, nerve palsy, and femoral head articular cartilage damage. We recommend either closed reduction with the patient under anesthesia followed by skeletal traction and delayed open reduction/internal fixation, or immediate open reduction/internal fixation if the reduction is not stable. PMID- 8433196 TI - Surgical treatment of displaced acetabular fractures: results of 50 consecutive cases. AB - Results of the surgical treatment of 50 consecutive displaced acetabular fractures were reviewed after a minimum of 2 years and a maximum of 6 years. Twenty-five fractures were complex, and 15 were treated at > or = 3 weeks postinjury. The quality of the reduction was anatomic in 74% of the patients. The rate of osteonecrosis of the femoral head was 10%. Heterotopic bone appeared in 24% of the patients, but function was impaired in only three. Excellent and good results were noted in 76% of the patients. Fractures operated on at > or = 3 weeks (delayed) had a failure rate of 40% compared with 17% for fresh fractures. The failure rate of delayed fractures was negatively influenced by nonoperative treatment initiated before surgery in other centers. Surgical treatment is considered the method of choice for displaced acetabular fractures, provided it is performed by knowledgeable and proficient surgeons. PMID- 8433197 TI - The effect of indomethacin on heterotopic ossification following acetabular fracture surgery. AB - Sixty-six patients with acetabular fractures requiring a posterior or extensile surgical approach were treated using a uniform protocol that was begun in July 1984. In 1987, prophylactic Indomethacin was added to the protocol to study its effects on the prevention of heterotopic ossification. Forty-six patients were operated on prior to and 20 after the initiation of the Indomethacin treatment program. Patients were observed for at least 6 months and the incidence in severity of heterotopic ossification between groups was compared using the Brooker classification. Patients' were also evaluated for associated risk factors. Statistical analysis revealed that the male sex and the extensile approach were the significant risk factors (p < 0.01). Evaluation of drug treatment revealed that while Indomethacin was not effective in completely eliminating heterotopic ossification, the occurrence of severe heterotopic ossification (Brooker Class III and Class IV) was significantly reduced (p < 0.05). PMID- 8433199 TI - Blood transfusions in hip fracture patients: implications for blood conservation programs. AB - To address the potential role of innovative blood conservation interventions in nonelective surgery, we reviewed blood transfusions and blood losses during hospitalization of patients undergoing open reduction internal fixation of an intratrochanteric hip fracture. Sixty-four orthopaedic patients consecutively admitted over a 3-year interval were analyzed for transfusion needs by calculating red blood cell (RBC) volume lost during hospitalization. Overall, 39 (61%) patients received blood. We found that the "transfusion-trigger" was higher for females compared to males. Fifteen (23%) of 64 patients were identified to have been transfused with RBC volumes in excess of RBC volumes lost. The remaining 49 patients determined to be untransfused or to be transfused appropriately received 1.4 +/- 2.1 blood units (M +/- SD). Of these, 30 (60%) received < or = 1 U. We found no evidence that patients who received blood transfusions in excess of blood losses benefited compared to those whose blood replacement was less than blood lost. We conclude that innovative blood conservation interventions such as recombinant human erythropoietin (EPO) therapy can be incorporated into this nonelective surgical setting and may permit a significant percentage of hip fracture patients to avoid homologous blood transfusion. An algorithm for physician education programs that can address blood transfusion practices is provided so that patients can benefit from new blood conservation approaches. PMID- 8433198 TI - Muscle strength testing following surgery for acetabular fractures. AB - A retrospective clinical analysis was performed on 30 patients who underwent surgery for acetabular fractures. In addition to clinical and radiographic evaluations, muscle strength was tested using an isokinetic dynamometer. Average follow-up time was 21 months. Joint surface and congruency were restored within 3 mm in 29 of 30 cases. The average hip score was 83. Eight patients had an unsatisfactory result. Only 14 patients had a normal gait, while seven patients had a Trendelenburg gait. The overall strength deficit was 27%. This mean strength deficit was highly correlated with the hip-rating score. The greatest loss of strength was in abduction, where the average deficit was 50%. The loss of abduction strength was significantly greater for patients operated on through posterior approaches. Among patients operated on through a Kocher-Langenbeck approach, those with transverse fractures had significantly larger losses of abduction strength than those with posterior wall fractures. PMID- 8433200 TI - Hip fractures: an increasing health care cost. AB - Studies in several countries have indicated that there is likely to be a dramatic increase in the number of hip fractures in the early part of the 21st century. At a time when health care costs are coming under close scrutiny internationally, the added financial burden of the increasing number of fractures is of concern. This study analyzes the cost of treating hip fractures in New Zealand in 1990 and projects forward the costs of treatment and the percentage of that portion of the government's health budget for the years 2001 and 2011. PMID- 8433201 TI - Pudendal nerve palsy after femoral intramedullary nailing. AB - Pudendal nerve palsy after femoral intramedullary (IM) nailing was retrospectively reviewed in 65 nailings performed on 63 patients. Ten pudendal nerve palsies (15%) were noted in eight male patients and two female patients. Three male patients had autonomic involvement affecting erections. All palsies were transient (3-173 days), and occurred in patients done in the supine position as opposed to the lateral position. A possible etiology is the smaller perineal post used in the supine position that may penetrate the pelvis deeper, compressing the pudendal nerve. Other factors may be operating time and amount of traction. As prevention, the perineal post must always be adequately padded, and the operating time and amount of traction should be minimized to decrease the incidence of pudendal nerve palsy. Because pudendal nerve palsy appears to be a common complication in femoral IM nailing, the patient must be informed of this possibility. PMID- 8433202 TI - Anterior margin articular fractures of the distal radius. AB - Twenty anterior articular margin distal radial fractures were treated in an 11 year period. The size of the articular fragment was determined by the lateral radiograph to be either < or > 50% of the articular surface. Seventeen patients were > 60 years of age, range: 40 to 78; average age: 67. Seven were initially treated by closed manipulation, but four lost position and were internally stabilized. The remaining 13 were primarily stabilized by application of an anterior plate. Twelve patients were followed > 2 years and eight > 5 years, with an average follow-up of 3.8 years. The greater loss of wrist extension in the smaller articular fragment group was statistically significant. All patients treated by plate stabilization returned to their prefracture activities. In this fracture, the T-plate proved to be a satisfactory stabilizing implant. PMID- 8433203 TI - The use of resonant frequency measurements for the noninvasive assessment of mechanical stiffness of the healing tibia. AB - A study was performed to assess the usefulness of measuring the resonant frequency of vibration of the tibia as a determinant of its flexural rigidity in fracture healing. The measurement system consisted of an electronic tapper that struck the anteromedial distal surface of the tibia and an accelerometer, held against the proximal surface, that received the response. Custom software displayed the frequency spectrum from which the first mode bending frequency of the tibia could be pinpointed. We have found that resonant frequency was highly correlated to the log of tibial flexural rigidity, with an exponent of 0.582 (r2 = 0.815). In human volunteers, a series of four tests at monthly intervals showed a reproducibility of approximately 3% (95% confidence interval) with no significant variability between right and left legs. In 14 patients with healing tibial fractures, resonant frequency ratio (healing/injured leg) was correlated to time ratio (time of test/time healed) by a second-order polynomial fit (r2 = 0.58). PMID- 8433204 TI - Effect of axial load and ankle position on ankle stability. AB - The range of motion of 10 fresh cadaveric ankle specimens was measured for flexion, anterior-posterior drawer, inversion-eversion, and internal-external rotation under conditions that simulated normal weight-bearing. At a 70 kg load, range of motion significantly diminished in all directions (p < 0.005). Plantar flexion was diminished to a greater degree than dorsiflexion. For anterior posterior drawer in the loaded state, ankle flexion did not play a significant role in determining stability. Factors such as ligamentous attachments may be more critical than mortise geometry in determining anterior-posterior translation. For torsion and version, stability was greatest in dorsiflexion. That ankle stability is related to articular congruity with increased load bearing emphasizes the importance of anatomical restoration of the ankle mortise in the injury state. PMID- 8433205 TI - Fractures of the shaft of the radius after treatment of Colles fractures with pins and plaster or external fixation. AB - Refracture of the radius through a pin site after the removal of pins and plaster or an external fixator for Colles fracture is rarely mentioned in the literature. We present the details of three such cases and review two others reported in the literature. Our aim is to alert orthopedists to the potential for this complication. Patients with superficial or deep pin tract infections appear to be at greater risk. PMID- 8433206 TI - A type IV Monteggia injury with a distal diaphyseal radius fracture in a child. PMID- 8433207 TI - Distal humeral replacement after failed continuous passive motion in a T-condylar fracture. AB - Comminuted osteoporotic intercondylar fractures of the distal humerus are a treatment dilemma. We report the case of an elderly patient with a type C3 T condylar fracture initially treated with continuous passive motion. This treatment resulted in a loss of medial stability. Pain relief and adequate function were achieved with a custom distal humeral replacement and repair of the medial collateral ligament. PMID- 8433208 TI - Fracture of the shaft of the humerus secondary to muscular violence. AB - Fractures of a normal humeral shaft secondary to muscular violence have been uncommonly reported in the literature since the early 1900s. These injuries have been associated with throwing javelins, hand grenades, and baseballs. We report a case of a similar injury occurring in a healthy young amateur baseball pitcher. Pertinent anatomy, pathomechanics, and electromyographic study results are discussed. PMID- 8433209 TI - Isolated fracture of the medial cuneiform. AB - We report a case of a 21-year-old man who sustained an isolated fracture of the medial cuneiform in a motorcycle accident. To our knowledge, this is the first report of such an injury. We describe his treatment, which included anatomical fixation of the fracture. PMID- 8433210 TI - Pathology and the nine ages of rheumatism. Advances in knowledge of the connective tissue diseases. PMID- 8433211 TI - The relationship between wall tension, lamellar thickness, and intercellular junctions in the fetal and adult aorta: its relevance to the pathology of dissecting aneurysm. AB - It is known that the distribution of stress and strain in the vessel wall is not uniform. We believe that this explains the location of the plane of dissection in dissecting aneurysms of large elastic arteries. We have investigated the effects of non-uniformity of stress and strain on the thickness of each elastic lamella and on the distribution of intercellular junctions in the media of developing and adult rats, to seek evidence to support this hypothesis. Intercellular junctions were identified by transmission electron microscopy of whole wall sections. A morphometric study of elastic tissue distribution was made on an image analysis computer. Differences were analysed using one-way analysis of variance. There are between six and eight elastic lamellae in the aorta of rats. In the fetus, only the internal elastic lamella is complete; the others were not fully formed by term. In the adult, the inner five elastic lamellae were thicker than the remaining two or three, and smooth muscle cells in the thicker lamellar units had more cell-cell contacts of all types examined. These data support the concept of a difference in stress-resisting properties of the aortic wall on the junctions between the inner two-thirds and the outer third of the media. The findings indicate that, as proposed in theoretical models the innermost lamellae support the high tension. In the adult aorta, the structure is modified to enhance the capacity to resist stress in the internal two-thirds of the media.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433212 TI - Immunohistochemical analysis of p53 protein overexpression in normal, premalignant, and malignant tissues of the cervix uteri. AB - Two hundred and thirty-eight cervical lesions ranging from normal to malignant were examined for overexpression of p53 protein. Whereas p53 protein was identified in 62 per cent of invasive squamous cell carcinomas, 11 per cent of invasive adenocarcinomas, and 7 per cent of squamous cell carcinomas in situ, no staining was found in adenocarcinoma in situ, dysplastic tissue, condyloma, and normal tissue. In 9 per cent of the positive cases of invasive squamous cell carcinomas, 5-50 per cent of the tumour cells were immunoreactive for p53 protein, whereas the other positive specimens were characterized by only rare p53 positive cells. We conclude that in invasive cervical carcinomas widespread overexpression of p53 protein is unusual, but occasional positive nuclei can be found frequently. Furthermore, our results indicate that altered expression of p53 protein may be involved in the progression of cervical carcinomas. PMID- 8433213 TI - Immunohistochemical analysis of the p53 oncoprotein on paraffin sections using a series of novel monoclonal antibodies. AB - Alterations of the p53 tumour suppressor gene are considered critical events in multistage carcinogenesis of a wide range of human cancers. In an attempt to elucidate the role of various p53 mutations in tumorigenesis and to investigate their relationship to the p53 protein accumulation and subcellular localization, we have raised a new series of 21 mouse monoclonal antibodies (MAbs) to human recombinant p53. The new MAbs (designated the Bp53 series) appear to recognize mainly denaturation-resistant epitopes in immunoblotting and the majority of them are suitable for immunostaining of p53 in cultured cells and frozen sections. Furthermore, at least three MAbs (Bp53-11, Bp53-12, and Bp53-28) proved to be reliable reagents for immunohistochemistry on paraffin-embedded specimens. The immunohistochemical analysis of paraffin sections from 118 human tumours of various histogeneses with Bp53-11 and Bp53-12 showed nuclear accumulation of the p53 protein in variable proportion of tumour cells in 76 cases (64 per cent). The influence of three parameters of tissue processing (type of fixative, period of fixation, and duration of autolysis) on p53 protein detection was also investigated. The results of this study provide the necessary basis for wider application of these novel MAbs as tools in both routine histopathology and functional analyses of the p53 oncoprotein. PMID- 8433214 TI - Detection of calcitonin and calcitonin gene-related peptide mRNA in human medullary thyroid carcinoma. A retrospective study. AB - In situ hybridization finds many applications in modern pathology. In many cases, special attention is paid to the processing of the tissues prior to in situ hybridization. In order to investigate the value of RNA in situ hybridization (RISH) in retrospective studies, we performed RISH for calcitonin and calcitonin gene-related peptide (CGRP)-I and -II mRNA in eight medullary thyroid carcinomas processed in 1981-1983. RISH was successful with radioactive calcitonin and CGRP I probes. With biotinylated probes, only calcitonin-specific probes gave adequate results. The concentrations of CGRP mRNA were probably too low to be detected by non-radioactive RISH. The results of RISH were correlated with the immunohistochemical localization of the polypeptides. The results matched in all cases except one, where hybridization for calcitonin mRNA was found, but no immunoreactive calcitonin polypeptide. We conclude that RISH can be successfully used for retrospective analysis, even after long storage of tissue embedded in paraffin. PMID- 8433215 TI - In situ correlation of synthesis and storage of parathormone in parathyroid gland disease. AB - The distribution and expression of parathyroid hormone (PTH) were investigated in normal and abnormal parathyroid tissue. PTH was detected using a monoclonal antibody with specificity for the 44-68 region of the PTH molecule. Prominent reactivity for PTH was seen in normal parathyroid with a granular pattern of staining. Active parathyroid tissue (adenoma and hyperplasia) showed much less reactivity for PTH, although there was prominent reactivity in the normal tissue around adenomas. Comparison of expression of PTH with that of parathormone mRNA showed a reciprocal pattern in normal tissue and, to a less marked extent, in abnormal tissue. Parathyroid carcinoma in particular had coinciding areas of PTH and PTH mRNA expression. Oxyphil cells had little or no PTH expression, except in the associated 'colloid' in some cases. The findings indicate an inverse relationship between storage and cellular synthesis of PTH, this being more marked in physiological than in pathological conditions of the parathyroid. PMID- 8433216 TI - Localization of plasminogen activator inhibitor-1 production in inflamed appendix by in situ mRNA hybridization. AB - The peritoneum has been shown to possess fibrinolytic activity which is thought to play a role in the prevention of intra-abdominal adhesion formation. Recently inflamed peritoneal tissue has been shown to have reduced fibrinolytic activity secondary to increased levels of plasminogen activator inhibitor-1 (PAI-1). The aim of this study was to localize the production of PAI-1 in appendix tissue using in situ mRNA hybridization. Sections of normal and inflamed appendix were hybridized with a digoxigenin-labelled cDNA probe. PAI-1 production was localized to both mesothelium and serosal blood vessel endothelium in all inflamed appendix samples. Cell identities were confirmed using immunohistochemistry directed against mesothelial and endothelial cell markers. Staining was not seen on 1 probe following ribonuclease digestion). The identification of the cells expressing the PAI-1 gene in peritoneum increases our understanding of the pathophysiological changes in fibrinolytic activity which occur in inflammation and may lead to adhesion formation. PMID- 8433217 TI - Gastric intestinal metaplasia type III cases are classified as low-grade dysplasia on the basis of morphometry. AB - The aim of this study was to try to place gastric intestinal metaplasia, type III (type III IM) in the stepwise chain of events from atrophic gastritis to cancer. A number of dysplastic, periulcer regenerative, and type III IM lesions were qualitatively diagnosed (and graded) blindly and independently by several pathologists. These lesions were further analysed by means of quantitative parameters, with the aim of differentiating dysplastic from regenerative changes. Inconsistencies between the qualitative and quantitative classification (about 7 per cent of cases) were eliminated and homogeneous groups (low-grade dysplasia, high-grade dysplasia, regenerative changes) were obtained. These cases were taken as the gold standard against which type III IM was compared. The results indicate that the great majority (91.4 per cent) of cases of type III IM fulfil the nuclear and architectural criteria for low-grade dysplasia. PMID- 8433218 TI - Electron microscopy of rectal biopsies in HIV-positive individuals. AB - A series of 83 rectal biopsies was examined by electron microscopy (EM), 78 from HIV-seropositive patients (64 with diarrhoea, 9 with weight loss, and 5 asymptomatic) and 5 from controls without risk factors for HIV infection. Although EM identified the likely cause of the diarrhoea in only nine cases, the majority of symptomatic HIV-seropositive patients had abnormal biopsies including the presence of tubuloreticular structures, loss of microvilli, and oedema and disruption of autonomic nerves. Neuronal abnormalities were particularly common in patients with cryptosporidiosis, but no ultrastructural marker was specific to 'pathogen-negative' diarrhoea. PMID- 8433219 TI - Ultrastructural aspects of tumour invasion in the central nervous system. AB - Tumour invasion in the central nervous system (CNS) was studied using a mouse melanoma cell model. Attention was concentrated on the third ventricle as this site is distant from any implantation artefact. Transmission electron microscopy (TEM) revealed the formation of tumour cell aggregates within the ventricle. Underlying ependymal cells showed loss of cilia and microvilli. Progressive thinning of the ependymal cells took place until continuity of the ependyma was lost through ependymal retraction. Tumour cells were then in direct contact with sub-ependymal neuroglial processes. Further invasion was then accomplished by penetration between neuropil processes, followed by tumour cell infiltration along the intact basement membrane of cerebral capillaries with displacement of astrocyte foot processes from the capillary basement membrane. PMID- 8433220 TI - Experimental adriamycin nephropathy. Fine structure, morphometry, glomerular polyanion, and cell membrane antigens. AB - Two doses of adriamycin (2 mg/kg i.v.) were administered to young adult rats with a 22-day interval and the kidneys were examined 51, 79, and 107 days after the first injection. Light microscopy showed early prominent intraglomerular microcystic spaces and progressive, though not severe, segmental glomerulosclerosis with focal interstitial scarring and round-cell infiltration. The main features of the ultrastructure were widespread fusion of foot processes, focal cytoplasmic rarefaction of podocytes, and non-specific sclerosis of the mesangium without signs of severe degenerative changes or mesangiolysis. The segmental microcystic structures corresponded to agglomerated intrapodocytic vacuoles. The scatter of glomerular polyanion sites visualized by polyethylenimine-phosphotungstic acid resembled that of control animals but the quantitative assessment revealed a significant reduction. CD4-positive cells were the predominant element of the interstitial infiltrates. Most of the infiltrating cells expressed Ia antigens, whereas Ia-positive intraglomerular resident mononuclear cells were depleted. The adriamycin lesion resembles the post-five sixths nephrectomy ablation nephropathy in the subpopulations of the interstitial infiltrate but differs from it in the reduction of intraglomerular resident macrophages, the absence of destructive mesangial damage, and reduced segmental glomerulosclerosis. The main feature is the prolonged damage of podocytes, especially of their cytoskeletal system. PMID- 8433221 TI - Disruption effects of carbon tetrachloride on rat liver microsomes. AB - Lipid fluidity in rat liver microsomes was assessed by the steady state fluorescence polarization of stearic acid labelled at positions 2, 7 or 12 with 9 anthroyl groups. Oxygen solubility and/or mobility was determined by measuring the quenching rate of different pyrene derivatives containing an aromatic group separated from the microsome surface by 1, 4 or 11 methylene groups. The fluorescence of these compounds, as well as that from methylpyrene and benzo(alpha)pyrene, was quenched by carbon tetrachloride. The effect of the latter compound and of n-heptanol on the fluorescence polarization of the anthracene derivatives and the quenching rate by oxygen was also determined. The results obtained indicate that the lipid order decreases and the solubility and/or mobility of oxygen increases towards the bilayer core. The addition of carbon tetrachloride decreases the order of the membrane and increases the rate of fluorescence quenching by oxygen. The largest effect of the additive on the fluorescence quenching rate by oxygen is observed at intermediate positions in the bilayer. n-Heptanol addition decreases the membrane order and increases the rate of fluorescence quenching by oxygen or carbon tetrachloride, the maximum effect being observed at the microsomal surface. The differences between the effects of the two additives are discussed in terms of their different localizations. Fluorescence quenching by oxygen is considerably more affected by carbon tetrachloride than fluorescence depolarization. In addition, the maximum effect takes place at different positions in the membrane.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433222 TI - Photoproducts of benzydamine and azapropazone: demonstration of their phototoxicity in vitro. AB - Red blood cell lysis, photosensitized by the products of the aerobic photolysis of benzydamine (1) and azapropazone (4), was investigated. Irradiation of a methanol solution of 1 and 4 under oxygen produces the photoproducts 3-hydroxy benzydamine, (2), 2-(3-dimethylaminopropyl)-1-benzylindazolin-3-one (3) and 3 dimethylamino-7-methyl-1,2,4-benzotriazine (5). The mechanism of the photodegradation of 1 was examined. Photoproducts 3 and 5 produce singlet oxygen as demonstrated by trapping with 2,5-dimethylfuran. The photohemolysis rate for the photoproducts 3 and 5 was enhanced by deuterium oxide and oxygen. No change was observed in the presence of reduced glutathione. The photohemolysis rate was low under anaerobic conditions. PMID- 8433223 TI - UmuC product contributes to the inhibition of dimer excision produced by thymine less-amino acid-less pretreatment in UV-irradiated Escherichia coli. AB - In UV-irradiated Escherichia coli, predamaged by thymine-amino acid starvation or a UV predose, a large amount of dimers may remain unexcised and may be tolerated by an error-free mechanism, which requires the function of uvr, recA and lexA genes. A possible role of the umuC gene in both the inhibition of dimer excision and the toleration of unexcised dimers is investigated. Data suggest that the UmuC gene product is not absolutely necessary for the inhibition of dimer excision in UV-irradiated thymine-less-amino acid-less pretreated cells, but that it contributes to it. However, the UmuC product does not seem to be involved in the toleration of unexcised dimers which is dependent on uvr, recA and lexA. PMID- 8433224 TI - Fe2+ ions and reduced glutathione--chemical activators of psoralen-sensitized photohaemolysis. AB - The influence of Fe2+ ions and reduced glutathione (GSH) on the haemolysis of erythrocytes photosensitized (366 nm) by psoralen (PUVA haemolysis) was investigated. PUVA haemolysis was induced by the low fluence rate (24 W m-2) and high fluence (greater than 150 W m-2) of UV-A irradiation. It has been shown that Fe2+ ions and GSH activated PUVA haemolysis at both fluence rates of irradiation. PUVA haemolysis activation by Fe2+ ions was more pronounced than that by GSH. It is supposed that activation caused by Fe2+ ions and GSH is connected with their ability to reduce lipid peroxides or psoralen peroxides with the subsequent formation of free radicals. The regeneration of endogenous Fe2+ by reduced glutathione is also possible. PMID- 8433225 TI - In vitro photosensitized lysis of red blood cells by an antifungal drug griseofulvin. AB - Human red blood cells (RBCs) were lysed by in vitro irradiation in the presence of the antifungal drug griseofulvin (GF). Effects of UVA fluence and GF concentration on photohaemolysis were examined under aerobic conditions. The photohaemolysis occurred at much lower fluence than that necessary for oxidation of the membrane lipids. UVA-irradiated solution of GF did not cause haemolysis. The photohaemolysis was colloid osmotic in nature because it was preceded by K+ leakage from the cells and was delayed in the presence of 30 mM sucrose in the medium. Even under anaerobic conditions, RBCs were lysed by irradiation with higher fluence than that required for aerobic photohaemolysis. Therefore, some phototoxic mechanism other than photosensitized oxidation is also involved in the photohaemolysis. PMID- 8433226 TI - On the feasibility of the modified mechanism of photodynamic therapy proposed by Leupold and Freyer. PMID- 8433227 TI - Another look at cow milk in the second 6 months of life. PMID- 8433228 TI - Changes in hepatic vitamin K1 levels after prophylactic administration to the newborn. AB - We undertook a study of hepatic concentrations of vitamin K (vitamin K1 or phylloquinone, vitamin K1-epoxide, and menaquinones) in 18 infants, ages 1-8 days, with or without vitamin K1 supplementation. The infants who had no supplementation had a total hepatic storage ranging between 0.1 and 0.9 micrograms. Also, hepatic storage of phylloquinone was poor (< 1 microgram) when compared with daily requirements. Moreover, we did not detect any menaquinone in the livers of these infants in our study. The prophylaxis applied to the other infants was very efficient. Hepatic vitamin K1 concentrations, obtained < 24 h after administration, were very high (62.8-93.5 micrograms/g). Vitamin K1-epoxide concentrations were high, which proved the efficiency of the vitamin K cycle. In contrast, the decrease in vitamin K1 concentrations was also very rapid, since the median value after 48 h was 8.4 micrograms/g and only 2.9 micrograms/g 5 days after administration. However, hepatic total storage after 5 days in one infant with vitamin K1 supplementation was much higher (112 micrograms) than in infants who had not received supplementation. In conclusion, hepatic phylloquinone storage at birth was poor (< 1 microgram). The newborn infant might be in a situation of potential deficiency. After prophylactic oral administration of phylloquinone, uptake by the liver was quite satisfactory, but concentrations dropped quickly. However, phylloquinone hepatic storage remained elevated (112 micrograms) after 5 days. PMID- 8433229 TI - Fecal chymotrypsin in infants fed different diets. PMID- 8433230 TI - Magnesium acetate vs. magnesium gluconate supplementation in short bowel syndrome. PMID- 8433231 TI - Sorting out the role of viral infections in autoimmune hepatitis. PMID- 8433232 TI - How thick is the jejunal unstirred water layer? PMID- 8433233 TI - To be HBV, or not to be; non-A, non-B is in question. PMID- 8433234 TI - Hormonal regulation of the mRNA for cysteine-rich intestinal protein in rat jejunum during maturation. AB - Cysteine-rich intestinal protein (CRIP) has been implicated as an important zinc binding protein in the rat intestine. However, its specific role remains undefined. As an approach to the ultimate elucidation of the function of CRIP, we have explored the role of glucocorticoids and L-thyroxine (T4) in the increase of CRIP mRNA that occurs during postnatal development. Hydrocortisone administration on day 10 elicited a precocious increase of CRIP mRNA. The response to hydrocortisone was readily detectable 12 h after injection. Lack of endogenous glucocorticoids in rat pups adrenalectomized on day 9 impeded but did not prevent the normal rise of CRIP mRNA. Furthermore, injections of dexamethasone (DEX) on days 10, 16, and 18 led to a loss of responsiveness of CRIP mRNA as the pups matured. The administration of T4 alone resulted in a small increase of CRIP mRNA, whereas when combined, T4 and DEX synergistically raised the concentration of CRIP mRNA. All of these patterns of response to hormone manipulation indicate the possibility that CRIP is a mediator of glucocorticoid action on the developing intestine. They do not appear to support the hypothesis that CRIP plays a role in zinc transport during the postnatal period. The potent effects of glucocorticoids and T4 on CRIP mRNA levels should provide useful tools for further investigations in this area. PMID- 8433235 TI - A randomized double-blind clinical trial of a maltodextrin-containing oral rehydration solution in acute infantile diarrhea. AB - A double-blind, randomized controlled study was used to compare the efficacy and safety of an oral rehydration solution either with minimally hydrolyzed maltodextrins or the standard recommended glucose. One hundred twenty pediatric patients with acute watery diarrhea (60 in each group) were studied, but only 116 patients were included in the final analysis. After rehydration, outcome variables did not differ significantly at p < 0.05. Mean duration of diarrhea was 52.5 +/- 32.2 h for the control group (median, 50.8 h) and 57.2 +/- hours for the study group (median, 45.3 hours). Comparisons of the mean stool output, weight gain, and ORS intake on the 24th h and from admission to discharge were not statistically significant. Differences in laboratory parameters consisting of mean serum sodium, potassium, total CO2, hematocrit, plasma total solids, urine specific gravity, and random blood sugar were likewise not significant. Differences in stool pH and reducing sugars were statistically significant; however, the observed values were still within normal range. All laboratory values improved upon rehydration. Replacement of glucose with maltodextrins did not offer added advantages in reducing the duration and severity of diarrhea. PMID- 8433236 TI - Rotavirus induces alpha-interferon release in children with gastroenteritis. AB - alpha-Interferon (IFN) blood levels were studied in 38 children hospitalized for rotavirus gastroenteritis. During rotavirus infection, a peak of systemic alpha IFN was observed within 2 days of onset of symptoms. There was a significant positive correlation between alpha-IFN levels and the number of vomiting episodes (p = 0.0003) but not with duration of vomiting, maximal temperature, and duration of fever. alpha-IFN levels were higher in children with peripheral cyanosis compared with children without peripheral cyanosis (p = 0.005) and tended to be higher in children with diarrhea of < 3 days' duration compared with those with diarrhea lasting > 4 days (p = 0.06). alpha-IFN could be partly responsible for the severity of such initial symptoms as vomiting and peripheral cyanosis in rotavirus gastroenteritis and could play a role in recovery from diarrhea. PMID- 8433237 TI - Rectal histopathology in endemic Shigella and Salmonella diarrhea. AB - Rectal histopathology was evaluated in 34 cases (2 months-12 yrs old) of endemic "invasive diarrhea" [> 20 WBCs per high-power field on stool microscopy with (RBC positive) or without (RBC negative) associated RBCs] where S. dysenteriae (n = 9), S. flexneri (n = 11), and nontyphoidal Salmonella were isolated as the sole identifiable enteropathogens. Persistent diarrhea (> 14 days duration) was more common with Salmonella infection whereas RBC-positive "invasive diarrhea" was more frequent with Shigella, particularly S. dysenteriae (all cases) infection. The histopathological profile was comparable to the earlier descriptions of infective colitis to a large extent and the nature of the infecting organism could not be determined on the basis of rectal histology alone. The other noteworthy features were as follows: (i) mild crypt distortion (26%) and branching (21%) in both Shigella and Salmonella infection; in Salmonella infection, dilation of the glands was significantly greater with persistent diarrhea; (ii) presence of chronic inflammatory cells either alone or in combination with neutrophils in 62%; a predominant neutrophilic response was significantly higher with S. dysenteriae infection and an acute presentation; (iii) pseudomembrane formation (six subjects; 18%) especially in S. dysenteriae (four cases); and (iv) a significant association of neutrophilic response, edema, and neutrophils within the vessels in the lamina propria and mucin depletion in the glands with RBC-positive "invasive diarrhea." PMID- 8433238 TI - Apple juice malabsorption: fructose or sorbitol? AB - Carbohydrate malabsorption after apple juice ingestion may produce abdominal symptoms and diarrhea, especially in children. The carbohydrates suggested to play roles in this process are fructose, as it is present in excess of glucose, and sorbitol. Absorption of the carbohydrates in apple juice was investigated in 17 children and 12 adults by means of the hydrogen breath test. Apple juice was given at a dose of 15 ml/kg body weight, with a maximum of 375 ml. Fructose (0.6 g/kg) and sorbitol (0.06 g/kg), alone and in combination, were administered in amounts similar to their contents in apple juice (fructose as excess over glucose content). Apple juice malabsorption, as judged by a peak breath H2 excretion of > or = 20 ppm, was found in 11 children (65%) and 4 adults (33%). Of those malabsorbing apple juice, 7 of 11 children malabsorbed fructose, 1 of 11 sorbitol, and 4 of 11 the combination; the four adults absorbed all test solutions completely. We could not find an additive effect of sorbitol on breath H2 excretion after fructose ingestion. Peak breath H2 concentrations after apple juice ingestion (mean +/- SEM: 43 +/- 7 ppm) were higher than those with fructose (23 +/- 5 ppm; p < 0.05) or the fructose-sorbitol combination (20 +/- 5 ppm; p < 0.05). Fructose, and not sorbitol, is the sugar responsible for the increase in breath H2 after apple juice consumption and therefore for the diarrhea accompanying excessive apple juice consumption in toddlers. PMID- 8433239 TI - Gastrointestinal blood loss in older infants: impact of cow milk versus formula. AB - Concerns that consumption of whole cow milk (WCM) by older infants may result in excessive gastrointestinal blood loss and subsequent iron deficiency led us to perform a prospective, randomized study in 104 infants. Infants were assigned to receive WCM beginning at 6 months or one of three formulas beginning at 4-6 months of age and followed until 12 months of age. Gastrointestinal blood loss was similar for all groups, as determined by both qualitative (Hemoccult II) and quantitative testing (HemoQuant). There was no association between concentration of fecal hemoglobin and volume of WCM consumed or iron status by 12 months of age. Of eight infants (seven WCM, one formula) who became iron-depleted, none had excessive fecal hemoglobin excretion. When pooled and analyzed regardless of feeding group, fecal hemoglobin increased with age and was greater at 11 and 12 months than at younger ages. We conclude that although infants fed WCM are at increased risk of developing iron depletion, the iron insufficiency is not due to gastrointestinal blood loss. We further conclude, based on our sample of normal infants age 4-12 months, that fecal hemoglobin concentrations of 0.5-0.8 mg/g stool correspond to the upper limits of normal, values much lower than in adults. PMID- 8433240 TI - Characterisation of the local inflammatory response in appendicitis. AB - In this study we have characterised the local inflammatory response in acute suppurative appendicitis (S), focal appendicitis (F), and normal appendices (C). Enumeration of lymphocyte subpopulations, cells expressing IL-2 receptor, natural killer (NK) cells, monocytes and plasma cell isotypes and subclasses infiltrating the lamina propria was carried out on all specimens using immunoperoxidase staining procedures. Total T cells were significantly increased in both acute suppurative appendicitis and focal appendicitis compared with controls (p < 0.001). Cells infiltrating the lamina propria expressed IL-2 receptor in all appendiceal specimens but were significantly increased in both acute and focal appendicitis (p < 0.01). IgG and IgA plasma cell isotypes were significantly increased in all S and F appendiceal specimens (p < 0.001). Monocyte and NK cell numbers, however, were only increased in acute suppurative appendiceal specimens. The increased lymphocyte and plasma cell isotypes seen in focal appendicitis occurred throughout the entire organ even through the inflammatory focus was confined to only three to seven serial sections. These results clearly show a differential pattern of cellular infiltration in focal appendicitis from that seen in acute suppurative appendicitis. The selective lymphocyte and plasma cell nature of the cellular infiltrate in the lamina propria of focal appendicitis may reflect the presence of a specific immune response to an as yet unidentified luminal antigen as a possible cause of appendicitis. PMID- 8433241 TI - The pathogenesis of biliary atresia: a morphological study of the hepatobiliary system and the hepatic artery. AB - Specimens of the extrahepatic biliary trees and wedge liver biopsies were studied in 11 cases of biliary atresia. The hepatic arteries at the porta hepatis were examined with ultrasound in five of the 11 cases. The basic histopathological features were found to be epithelial damage and an inflammatory, sclerosing change of both the intrahepatic and the extrahepatic biliary trees, combined with an arteriopathy manifesting as hyperplasia and hypertrophy of the hepatic arteries in all cases. Based on the results of ultrasonography and histological examination, this arteriopathy was thought to affect the arteries from the trunk of the common hepatic artery to its peripheral branches supplying the entire biliary tree. To determine whether these morphologically abnormal hepatic arteries are related to the pathogenesis of biliary atresia in association with abnormal blood flow and pressure requires further investigation. PMID- 8433242 TI - Indocyanine green test is a reliable indicator of postoperative liver function in biliary atresia. AB - In order to evaluate liver function in postoperative biliary atresia (BA) patients, the indocyanine green (ICG) clearance test was performed. Nineteen patients, ranging in age from 2 to 9 years, were classified into three groups. Group I were those who had no jaundice throughout the postoperative period (n = 9), Group II were those who had recurrent or intermittent jaundice (n = 7), and Group III were those who had persistent jaundice after hepatic portojejunostomy (n = 3). Forty-four volunteers of comparative age and sex served as controls to establish a normal range of ICG-K values in infants and children. The normal minimal ICG-K value in those 2-9 years of age was defined as 0.19. ICG-K values in BA patients were 0.262 +/- 0.073 (Group I), 0.150 +/- 0.060 (Group II), and 0.054 +/- 0.011 (Group III). All nine patients with ICG-K below the normal level had esophageal varices, and seven of nine had a history of gastrointestinal hemorrhage. Two patients with ICG-K values within the normal range had esophageal varices, and none had a history of gastrointestinal hemorrhage. Five of nine patients with ICG-K values below normal had low serum albumin levels, and all had low prealbumin levels. Of those with ICG-K within the normal range, none had low serum albumin or prealbumin levels. On the other hand, serum bilirubin and other liver function tests did not accurately reflect clinical findings. In conclusion, the ICG test using the ICG-K value was confirmed to be a reliable indicator of postoperative liver function in BA patients. PMID- 8433243 TI - Horizontal transmission of hepatitis B virus in children. AB - Horizontal transmission of hepatitis B virus (HBV) is responsible for about half of the hepatitis B surface antigen (HBsAg) carriers in Taiwan. To investigate the routes and risk factors of horizontal HBV transmission, 131 HBsAg carrier children of HBsAg seronegative mothers were compared with 98 age-matched children seronegative for all hepatitis B markers. Possible factors influencing transmission of HBV, including family size, age at attending kindergarten, frequency of intramuscular injection during infancy and at the toddler stage, contact with HBsAg carriers, and HBV status of parents, siblings and caretakers were studied by questionnaire survey. Intramuscular injection frequency during infancy and at the toddler stage and prevalence of HBsAg positivity among siblings were significantly higher in carrier children than in the control group. Other factors studied were not different in these two groups. The results indicated that unsterilized, multiple intramuscular injections and intrafamilial spread among siblings might be the major routes of horizontal HBV transmission in children in Taiwan. PMID- 8433244 TI - Ingestion of caustic alkali farm products. AB - Since the Poison Prevention Packaging Act took effect, the number of ingestions of caustic alkali from household products has been significantly reduced. Commercial caustic alkalis used on farms, however, were not included in this legislation. Fourteen children over a 5 year period were seen after ingestion of commercial caustic alkalis used on farms. Seven of the children had ingested liquid pipeline cleaners and seven had ingested solid agents used for a variety of reasons. Six of seven children ingesting liquid agents did so from nonoriginal containers into which the caustic had been transferred for convenience. All seven children ingesting solid agents did so from the original container. Eight of the 14 children were found to have second-degree or worse esophageal involvement. Both solid and liquid caustic agents used commercially on farms can cause significant morbidity. Development of a child-resistant container for daily transfer of liquid pipeline agents could be helpful in preventing injuries from liquid pipeline cleaners. Pediatric gastroenterologists as well as primary care physicians in rural areas should be familiar with this type of injury and should take an active role in instructing parents of children living on farms to prevent such injuries. Extension of the Poison Prevention Packaging Act to caustic alkalis used on farms needs to be considered. PMID- 8433245 TI - Intracranial hemorrhage due to vitamin K deficiency in breast-fed infants with cholestasis. PMID- 8433246 TI - Arterioportal fistula in infancy. PMID- 8433247 TI - Acquired colonic atresia: a rare sequela of necrotizing enterocolitis. PMID- 8433248 TI - Congenital esophageal stenosis treated by balloon dilation. PMID- 8433249 TI - A comparison of polylactic acid granules and decalcified freeze-dried bone allograft in human periodontal osseous defects. AB - The purpose of this study was to compare the effectiveness of polylactic acid (PLA) granules as an alloplastic grafting material to that of decalcified freeze dried bone allograft (DFDBA) and a flap procedure for debridement without graft (FPD) when treating periodontal intrabony defects. Ten patients presenting with advanced adult periodontitis, including at least 3 similar periodontal osseous defects (2- and 3-walled), comprised the study group. After completion of a hygienic phase of treatment, measurements were made with calibrated periodontal probes and stents to determine soft tissue recession, probing pocket depths, and probing attachment levels. Each defect was surgically exposed and hard tissue measurements were obtained. Defects were treated with one of the 3 methods above chosen randomly prior to the surgical appointment. Six months postsurgery, soft tissue measurements were repeated and all sites were surgically reentered to obtain hard tissue measurements. All surgical sites healed without clinical complication. The initial pocket depths and initial depth of osseous defects were compared between the groups using ANOVA and no significant differences were found. A mean osseous defect fill of 0.4 mm (11.2%) occurred with the flap procedure for debridement, 3.0 mm (65%) with DFDBA, and 0.1 mm (2.2%) with PLA. Mean crestal bone loss was 1.30 mm for FPD, 0.60 mm for DFDBA, and 1.55 mm for PLA. No statistically significant differences were found in soft tissue recession between groups or in the osseous defect measurement between PLA and FPD. A statistically significant improvement (P < 0.001) was found in the fill of the osseous defects when using DFDBA compared to the initial defect depth and to the other 2 groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433250 TI - Immunohistochemical distribution of extracellular matrix proteins as a diagnostic parameter in healthy and diseased gingiva. AB - This study showed histopathological findings of the extracellular matrix in healthy, inflamed, and hyperplastic human gingiva with immunohistochemical techniques. The distribution of collagen types V and VI, as well as of glycoprotein fibronectin, shows that they are extracellular matrix structural components which differentiate the tissue pathology. The orientation of the collagen fibers, the intensity of the fluorescent staining, the thickness of the fibrillar component, and the topographical localization of the connective tissue proteins are important parameters for tissue morphology. Therefore, bacterial deposits and the pharmacodynamic properties of drugs associated with gingival hyperplasia lead to an alteration of the matrix compared to the healthy tissues. This may be important in the tissue pathology in cases when the medical history of the patient is not known, as well as in forensic medicine. PMID- 8433251 TI - In situ characterization of gingival mononuclear cells in rapidly progressive periodontitis. AB - Rapidly progressive periodontitis (RPP) has been suggested as a distinct clinical entity within the spectrum of early onset periodontitis. Immunological mechanisms have been considered in the pathogenesis of RPP. This study was designed to evaluate the distribution and phenotypic properties of the lymphocyte populations within the affected gingival tissue of patients with RPP. Biopsies were obtained from 16 patients between 22 and 33 years of age. The tissue samples were processed for both histopathological and immunohistochemical examinations. Gingival tissue T lymphocytes (CD3+), helper T cells (CD4+), suppressor-cytotoxic T cells (CD8+), and cells positive for HLA-DR antigen were identified using monoclonal antibodies with an immunoperoxidase technique. Intracytoplasmic immunoglobulin-containing cells were also stained immunohistochemically with polyclonal antibodies. CD3+ cells were mainly located beneath the pocket epithelium. CD4+ and CD8+ cells were evenly distributed within this T-cell infiltrate with a CD4+/CD8+ ratio of 1:12. Numerous HLA-DR+ cells were also observed in the lymphocytic infiltrates. The majority of mononuclear cells located throughout the stroma were IgG+ plasma cells. Our results indicate that RPP patients present an IgG-bearing plasma cell dominated lesion with equal participation of both T-cell subpopulations. These findings suggest that activation and proliferation of B-cells play an important role in the pathogenesis of periodontal diseases. PMID- 8433252 TI - Cryopreserved cancellous bone allograft in periodontal intraosseous defects. AB - The purpose of this study was to evaluate the potential of cryopreserved cancellous bone allograft (CCBA) in the treatment of intraosseous periodontal defects compared to surgical debridement alone (DEBR). Cancellous bone was procured from femur heads that had been extracted for hip prosthesis procedures and cryopreserved in liquid nitrogen (-196 degrees C) in a tissue bank. Ten patients without systemic disorders and advanced periodontal disease (at least 2 intraosseous defects) participated in this investigation. Measurements from the cemento-enamel junction were made after initial therapy for clinical attachment level; also gingival recession, probing pocket depth, plaque index, and gingival index and, at the time of surgery, alveolar crest height and osseous defect depth were measured. All measurements were repeated at 1 year-reentry. Sixteen defects were debrided and grafted (test sites) and 13 defects were debrided only (control sites). Soft tissue measurements showed no statistical differences between the 2 groups. Defect fill was significantly greater with CCBA (1.75 mm) than with DEBR (0.56 mm). Defect depth reduction was 2.06 mm for CCBA and 0.78 mm for DEBR. These values correspond to a percent-defect resolution of 60% for CCBA and 29% for DEBR. Hard tissue measurements showed significant differences between the 2 groups. CCBA seems to be effective in the short-term treatment of intraosseous periodontal defects. PMID- 8433253 TI - Clinical evaluation of the effect of tetracycline root preparation on guided tissue regeneration in the treatment of Class II furcation defects. AB - The purpose of this clinical trial was to evaluate the effect of tetracycline root preparation on guided tissue regeneration in the treatment of Class II furcation defects. Nine pairs of defects with horizontal clinical attachment level value > or = 5 mm comprised the study group. Measurements were made to determine presence of plaque, gingival condition, probing depth, and vertical and horizontal clinical attachment level. Defects from each pair were randomly assigned for treatment with an expanded polytetrafluoroethylene membrane (e-PTFE) and tetracycline root conditioning (100 mg/ml) or the membrane alone. The membranes were removed 4 to 6 weeks postsurgery. Patients were then seen monthly for the duration of the study. Six months postsurgery, all clinical measurements were repeated. Following either treatment, improvement was observed in all clinical parameters, particularly in horizontal clinical attachment level. However, there was not a statistically significant difference in the improvement observed between sites treated with guided tissue regeneration in conjunction with tetracycline as compared to membrane placement alone. Further studies are needed to fully evaluate tetracycline root preparation in conjunction with regenerative therapy. PMID- 8433254 TI - Retention of antimicrobial activity by human root surfaces after in situ subgingival irrigation with tetracycline HCl or chlorhexidine. AB - Substantivity of tetracycline HCl and chlorhexidine digluconate was assessed in extracted teeth. Fifty periodontally compromised teeth scheduled for extraction with probing depths ranging between 6 and 12 mm were root planed and then irrigated in situ with 1 of 4 solutions: tetracycline HCl at concentrations of 10 or 50 mg/ml, 0.12% chlorhexidine digluconate, or 0.9% sterile saline. Each tooth was exposed to 150 ml of the respective irrigation solution. Following extractions, the teeth were transferred to tris buffered saline and incubated at room temperature for 22 days. Incubation solutions were replaced at 24-hour intervals. Removed solutions were examined for desorbed antimicrobial activity using a microtiter assay in which bacterial growth was evaluated by optical density readings. Tetracycline HCl 50 mg/ml exhibited significantly greater antimicrobial activity than chlorhexidine digluconate for 12 days and greater than saline for 16 days. Tetracycline HCl 10 mg/ml exhibited significantly greater antimicrobial activity than chlorhexidine digluconate and saline for 4 days. Chlorhexidine digluconate did not exhibit any significant antimicrobial activity at any time point. Our findings demonstrate long-lasting substantivity of tetracycline HCl, but not chlorhexidine digluconate, by teeth exposed to a single episode of pocket irrigation of their periodontally-exposed roots. The amount of antimicrobial activity retained is proportional to the concentration of tetracycline HCl used for irrigation. PMID- 8433255 TI - Mitogenic effects of growth factors on human periodontal ligament cells in vitro. AB - Periodontal regeneration is thought to require the migration and proliferation of periodontal ligament cells. Evidence suggests that the polypeptide growth factors PDGF, IL-1, and TGF-beta are mediators of these cellular events in wound healing. The purpose of this study was to determine the effects of these growth factors on human periodontal ligament (PDL) cell mitogenesis, and to identify the regulatory influences of TGF-beta on the response to PDGF and IL-1. Confluent, quiescent human PDL cells were cultured in vitro and treated with the polypeptide growth factors PDGF-AA and -BB, IL-1 beta, and TGF-beta in both a dose and time dependent manner. Mitogenic activity, as a measure of proliferative potential, was determined by the quantitation of 3H-thymidine incorporation during DNA synthesis. The results of this study demonstrated that both PDGF-AA and -BB enhance mitogenic activity in a dose-dependent manner over a concentration range of 1.0 to 50.0 ng/ml. IL-1 beta (0.01 to 1.0 pM) resulted in no mitogenic enhancement, and at high concentrations (10.0 to 100.0 pM) demonstrated an inhibitory effect. TGF-beta produced a significant increase (P < 0.01) in mitogenic activity (although relatively much less than PDGF) in a delayed, bimodal, dose-dependent manner over a concentration range of 0.01 to 20.0 ng/ml, with a maximal response at a concentration of 1.0 ng/ml. Additionally, incubation with TGF-beta at 1.0 ng/ml prior to the addition of PDGF significantly enhanced (P < 0.01) the mitogenic response to both PDGF-AA and PDGF-BB.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433256 TI - Occurrence and resolution of focal epithelial hyperplasia in two siblings with leukocyte adhesion deficiency. AB - Focal epithelial hyperplasia is an uncommon disorder characterized by formation of multiple asymptomatic oral mucosal papular and/or nodular lesions. This article relates the occurrence and clinical course of FEH in 2 adolescent siblings with leukocyte adhesion deficiency. Histological findings are described and insights into potential causes are discussed. PMID- 8433257 TI - Tetracycline inhibition and the cellular source of collagenase in gingival crevicular fluid in different periodontal diseases. A review article. AB - Tetracyclines have recently been shown to inhibit the activity of some but not all mammalian matrix metalloproteinases believed to mediate periodontal destruction. However, the specificity of this effect, which could have significant therapeutic implications for different periodontal diseases, has not been examined in detail. Doxycycline and 4-de-dimethylaminotetracycline (CMT-1) have been tested in vitro for their ability to inhibit human neutrophil and fibroblast interstitial collagenases and collagenase in human gingival crevicular fluid (GCF). The GCF samples were obtained from systemically healthy and insulin dependent diabetic adult periodontitis patients and from localized juvenile periodontitis (LJP) patients. The concentrations of these 2 tetracyclines required to inhibit 50% of the collagenase activity (IC50) were found to be 15 to 30 microM for human neutrophil collagenase and for collagenase in GCF of systemically healthy and diabetic adult periodontitis patients. These concentrations approximate the tetracycline levels observed in vivo during treatment with these drugs. In contrast, human fibroblast collagenase and GCF collagenase from LJP patients were both relatively resistant to tetracycline inhibition; the IC50 for doxycycline and CMT-1 for these 2 sources of collagenase were 280 and 500 microM, respectively. Based on these and other findings, we propose the following: 1) that systemic levels of tetracycline may inhibit connective tissue breakdown by inhibiting neutrophil collagenase; 2) that tetracyclines do not inhibit fibroblast-type collagenase, which may help explain their lack of effect on normal connective tissue remodeling; 3) that tetracycline inhibition of collagenases may serve to identify the cellular origin of the enzyme; and 4) that tetracyclines can also prevent the oxidative activation of latent human procollagenases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433258 TI - Development of the murine periodontium. I. Role of basement membrane in formation of a mineralized tissue on the developing root dentin surface. AB - The presence of basement membrane components on the forming root surface suggests a role for this structure during cementoblast differentiation. The purpose of this study was to investigate the role of root-associated basement membrane (RBM) in murine cementogenesis using tissue separation and recombination techniques. Root dentin specimens, with or without RBM, were combined with dental sac tissue, cultured for 2 weeks, harvested, and examined by light, immunofluorescence, and electron microscopy. Recombinations in which RBM was preserved on the root dentin surface were characterized by formation of an adherent mineralized tissue resembling acellular cementum; recombinations in which RBM was excluded were characterized by formation of mineralized tissue which did not adhere to the root dentin surface. These results suggest that formation of an adherent mineralized tissue on the developing root dentin surface is dependent upon the presence of indigenous basement membrane components. PMID- 8433259 TI - The diagnosis and assessment of depression, mania, and psychosis by self-report. AB - We examined the usefulness of the Minnesota Multiphasic Personality Inventory (MMPI), the original and revised versions of the Millon Clinical Multiaxial Inventory (MCMI and MCMI-II), and the Symptom Checklist-90-R (SCL-90-R) for the diagnosis and assessment of depression, mania, and psychosis in a heterogeneous group of 272 psychiatric inpatients. We examined the following: diagnostic efficiency of single scales at specified cutoff scores for these conditions, multidimensional test profiles, MMPI high-point codes, and associated MCMI and MCMI-II personality disorders. The reported findings are discussed in terms of how these tests may and may not be used to answer particular assessment questions and what the self-report vantage contributes to the entire clinical assessment process. PMID- 8433260 TI - MMPI-2 profiles of battered women in transition. AB - Domestic violence is a widespread problem in our society that has not been extensively studied using psychological assessment tools. In this investigation, the psychological functioning of battered women in transition was examined through the use of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Thirty-one women (M age = 30 years, M education = 11.5 years) were evaluated as residents in a confidential shelter operated by Women Against Abuse. All subjects were asked to complete the MMPI-2 as well as information on their history of length, severity, and types of abuse (i.e., physical and/or psychological). Results indicated elevated MMPI-2 profiles in 90% of the subjects with the most frequent code type being a combination of Scales F, 4, 6, and 8. Scales 2 and 7, which are often associated with depression, anxiety, and other forms of subjective distress, were not consistently elevated. Supplementary MMPI-2 scales revealed elevations on scales MAC-R, Mt, PK, and PS. Regression analysis indicated significant relationships between length and severity of psychological forms of abuse and overall levels of psychological distress (i.e., F scale and average clinical T-score). Age and physical forms of abuse were not related to MMPI indices of psychological disturbance. Theoretical issues of domestic violence, intervention strategies with battered women, and the dangers of misdiagnosis are discussed. PMID- 8433261 TI - Differentiating neuropathology from psychopathology with longitudinal and retrospective data: report of a case. AB - This case study report of diagnostic psychological testing considers the implications of a 53-point verbal-performance IQ differential, with the benefit of neuropsychological and neuroradiologic imaging studies, a 6-month follow-up Wechsler Adult Intelligence Scale-Revised (WAIS-R; Wechsler, 1981) evaluation, and retrospective examination of early school records and test findings. The approach highlights the limitations of cross-sectional clinical studies in differential diagnosis, particularly when both psychodynamic and neuropsychological factors are at issue. This report demonstrates how an early acquired neurodevelopmentally based deficit can alter or restructure the appearance of adult cognitive-perceptual functions. Further, early neurodevelopmental impairment is considered from the standpoint of its influence on compromised autonomous ego functions. PMID- 8433262 TI - Integrating the Rorschach and the MMPI in clinical assessment: conceptual and methodological issues. AB - The Rorschach and Minnesota Multiphasic Personality Inventory (MMPI) are among the most widely used personality assessment tools. However, there is little guidance in the literature about their combined use. In this article, I discuss conceptual and methodological issue of combining these widely used psychological tests, including the use of the test battery and the necessity of rationales for test utilization. Methodological approaches to integrating the test findings are discussed, including score, construct, test by test, and theory-based integrative approaches. The value of a person-centered interpretive and integrative focus is affirmed. PMID- 8433263 TI - Combining the Rorschach and the MMPI in the assessment of adolescents. AB - We examined empirical findings related to the integration of the Rorschach and the MMPI in assessing adolescents. Intercorrelations between 50 Rorschach variables and the 13 MMPI basic scales are reported for a clinical sample of 197 adolescents. Significant correlations only slightly exceeded the number expected by chance. A review of six additional studies of adolescent samples also generally revealed either very modest or nonsignificant relationships between the Rorschach and the MMPI. These findings leave open the possibility that combining data from the two instruments may increase incremental validity, an issue that should be assessed by using multivariate analyses. Guidelines for integrating Rorschach and MMPI data in clinical practices with adolescents are provided. PMID- 8433264 TI - A strategy for integrating a normal MMPI-2 and dysfunctional Rorschach in a severely compromised patient. AB - Effective assessment practice is dependent on synthesizing data from multiple sources. Our standard literature and experimental data base does not supply all the information practitioners need to provide assessment services. Practitioners must engage in a variety of novel operations to generate an acceptable assessment product. The role of the practitioner may be conceptualized as an independent contributor to the knowledge base underlying assessment. In this article, I articulate a series of stages serving as a guideline in integrating discrepant data from a Minnesota Multiphasic Personality Inventory-2 (MMPI-2) and Rorschach for a disturbed patient. The integrated data provides a more precise understanding of the patient than either data set by itself. PMID- 8433265 TI - The impact of response frequency on the Rorschach constellation indices and on their validity with diagnostic and MMPI-2 criteria. AB - I first examined the effects of response frequency (R) on the Comprehensive System's constellation indices (Exner, 1991). R is significantly associated with 26 of the 29 constellation criteria that are based on raw numbers and significantly correlated with total scores on each of the constellations. I then examined how R impacts the external validity of the constellations. The ability of the Schizophrenia Index and the Suicide Constellation to discriminate diagnostic groups appears to be impaired when protocols deviate from average length, whereas the Hypervigilance Index (HVI) appears most diagnostic of a paranoid condition when it is relatively elevated in brief records. R also clearly mediates the relationship between the Rorschach and Minnesota Multiphasic Personality Inventory-2 (MMPI-2) criteria. In lengthy protocols, many of the cross-method convergent correlations between appropriate MMPI-2 scales and the Depression Index, Obsessive Style Index, and HVI are quite high and approach the maximum found in personality research. In brief protocols, there are strong negative correlations between these constellations and self-reports of depression and interpersonal distress. Implications from these findings for the integration of assessment methods are discussed. PMID- 8433266 TI - Sex differences, sex roles, and projection on the TAT: matching stimulus to examinee gender. AB - We examined the assumption that on the Thematic Apperception Test (TAT) examinees identify more with stimulus characters of the same sex as themselves and therefore produce more projective material when tested with these gender matched cards. Repeated measures analyses of variance and t tests showed no increase in projection as a result of matching gender or sex role of subject to card stimulus. Results do not support the clinical utility of the separate male and female sets of TAT cards. PMID- 8433267 TI - Parental and relationship representations and experiences of depression in college students. AB - Young adults' descriptions of their parents and their relationships with their parents were used to reexamine the relations between object representation and depressive experience. One hundred eight students completed (a) four open-ended descriptions, including two written descriptions of the parents (mother and father, separately), and two written descriptions of the relationships with the parents; and (b) the Depressive Experience Questionnaire. Each of the four open ended descriptions was rated on seven scales. Factor analysis yielded four distinct factors from the 28 dimensions of the descriptions. These factors were related to: (a) the degree of elaboration and investment, (b) the structural level of the descriptions, (c) the affective tone of the description of the father, and (d) the affective tone of the description of the mother. Significant differences and interactions were found regarding the interplay between the specific significant other represented (father or mother) and the specific framework of representation (parent description or relationship description). Measures derived from parents' and relationship descriptions significantly predicted depressive experiences of self-criticism and dependency. The results indicate the advantages of a joint exploration of the representation of distinct significant others (mother and father) and the use of two modes of relatedness (describe parent and describe relationship with parent) in the process of personality assessment. PMID- 8433268 TI - Measuring the impostor phenomenon: a comparison of Clance's IP Scale and Harvey's I-P Scale. AB - Many of the discrepancies reported to date in empirical investigations of the impostor phenomenon (IP) may be due in part to (a) the use of different methods for identifying individuals suffering from this syndrome (impostors), (b) the common use of a median split procedure to classify subjects and (c) the fact that subjects in many studies were drawn from impostor-prone samples. In this study, we compared the scores of independently identified impostors and nonimpostors on two instruments designed to measure the IP: Harvey's I-P Scale and Clance's IP Scale. The results suggest that Clance's scale may be the more sensitive and reliable instrument. Cutoff score suggestions for both instruments are offered. PMID- 8433269 TI - Toward a conceptual understanding of the deviant response in the Comprehensive Rorschach System. AB - We examined the scoring criteria, subtypes, and interpretative nuances of the deviant response (DR) special score of the Comprehensive Rorschach System. To augment the usual understanding of the DR score, we review the concepts of fabulizing and confabulation in Rorschach literature and discuss the traditional meaning of and the confusion surrounding these terms. By equating a subtype of DR, the excessively embellished DR response, with Rapaport's (Rapaport, Gill, & Schafer, 1968) "affect-laden fantasy" type of confabulation response, we set the stage for an examination of the unique clinical diagnostic implications of this special subtype of DR. We conclude by recommending slight modifications to some of the special scores categories (DR in particular) of the Comprehensive System so that these scores can not only be assigned with more internal consistency and precision but also become more useful in identifying a broader range of unusual Rorschach responses. PMID- 8433270 TI - Attitude accessibility as a moderator of autonomic reactivity during decision making. AB - Attitude functionality was assessed in 2 experiments examining attitude accessibility as a moderator of physiological responses during decision making. In Study 1, experimental Ss but not controls rehearsed attitudes toward novel objects (abstract paintings). Subsequently, all Ss made rapid preference judgments for pairs of the paintings. In Study 2, attitudes were rehearsed by all Ss toward 1 of 2 mutually exclusive sets of abstract paintings. During the subsequent decision-making task, half the Ss made rapid pairwise preference judgments for rehearsed abstract paintings and half for pairs from the unrehearsed set. Autonomic measures were recorded continuously throughout both experiments. As predicted, in both experiments less autonomic reactivity was evident during the criterion pairwise preference task for groups for whom attitude rehearsal was relevant to the criterion task. PMID- 8433271 TI - Emotional expression and the reduction of motivated cognitive bias: evidence from cognitive dissonance and distancing from victims' paradigms. AB - Two experiments tested whether expression of emotions from which motivated cognitive biases presumably provide protection would reduce the extent of such biases. In Study I, we hypothesized that expressing any tension produced by writing a counterattitudinal essay would reduce the extent of dissonance-reducing attitude change. To test this hypothesis, Ss were induced to write an essay arguing for higher tuition. High-choice Ss were either encouraged to express their emotions, to suppress them, or to do neither. As expected, high-choice express Ss exhibited the least attitude change. Study 2 tested the hypothesis that expressing fear of cancer would reduce the extent of defensive distancing from cancer patients, but expressing sympathy would not. Although control Ss clearly distanced from cancer patients, fear-expression Ss did not. Implications for understanding the role of affect in defense are discussed. PMID- 8433272 TI - Pluralistic ignorance and alcohol use on campus: some consequences of misperceiving the social norm. AB - Four studies examined the relation between college students' own attitudes toward alcohol use and their estimates of the attitudes of their peers. All studies found widespread evidence of pluralistic ignorance: Students believed that they were more uncomfortable with campus alcohol practices than was the average student. Study 2 demonstrated this perceived self-other difference also with respect to one's friends. Study 3 traced attitudes toward drinking over the course of a semester and found gender differences in response to perceived deviance: Male students shifted their attitudes over time in the direction of what they mistakenly believed to be the norm, whereas female students showed no such attitude change. Study 4 found that students' perceived deviance correlated with various measures of campus alienation, even though that deviance was illusory. The implications of these results for general issues of norm estimation and responses to perceived deviance are discussed. PMID- 8433273 TI - Delayed costs of suppressed pain. AB - The study demonstrates that the rebound effect of thought suppression (Wegner, 1989) has an analog in the experience of somatic discomfort. During a cold pressor pain induction, 63 Ss were instructed either to concentrate on their room at home (distraction), to pay close attention to their hand sensations (monitoring), or to remove awareness of those sensations from mind (suppression). Two min of postpressor pain ratings showed that monitoring produced the most rapid recovery from the pain and that suppression produced the slowest. Suppression also contaminated the interpretation of a subsequent somatic stimulation; later in the experimental hour, Ss who had suppressed their cold pressor discomfort rated an innocuous vibration as more unpleasant than did other Ss. The strategies are discussed for their necessarily distinct processes of goal evaluation and their possibly differential drain on perceived coping capacities. PMID- 8433274 TI - Effects of talking about a stressful event on arousal: does what we talk about make a difference? AB - In Study 1, 30 male and 30 female undergraduates viewed an affect-neutral stimulus and a stress-inducing stimulus. Ss then talked about either their emotional reactions to the stressful stimulus (emotion condition), the sequence of events within it (fact condition), or the sequence of events within the neutral stimulus (distraction condition). Emotion-condition Ss were more autonomically aroused during a 2nd exposure to the stressful stimulus than were fact-condition Ss. In Study 2, 48 hr separated Ss' talking about their 1st exposure to the stressful stimulus from their 2nd exposure to it. Emotion condition Ss had lower levels of autonomic arousal while viewing the stimulus again and reported more positive affect after watching it than did fact-condition Ss. These results are discussed in the context of cognitive appraisal, perceptual motor, and self-disclosure views of emotion. PMID- 8433275 TI - Maintaining perceptions of control: finding perceived control in low-control circumstances. AB - Three questions about the role of perceived control in coping with a major life stressor were addressed in a sample of 71 cancer patients. As expected, those with greater perceptions of control were less depressed, even when physical functioning, marital satisfaction, and negative affectivity were controlled for. Consistent with a compensatory model of control, it was more important for patients to believe that they could control daily emotional reactions and physical symptoms than the course of the disease. Patients who endorsed irrational beliefs had lower overall perceptions of control. The results indicated that even patients who were physically or psychosocially worse off were better adjusted if they had higher perceptions of control. PMID- 8433276 TI - Simian immunodeficiency virus infection via amniotic fluid: a model to study fetal immunopathogenesis and prophylaxis. AB - The rising prevalence of infection with the human immunodeficiency virus type 1 (HIV-1) in young women will increase the number of infected children worldwide. Because HIV-1 seems to be transmitted mostly intrapartum, fetal infection probably occurs mainly via skin or mucous membrane exposure. A model for this route of fetal infection has been established in primates. After injecting the simian immunodeficiency virus (SIV) into amniotic fluid during late gestation, six of seven rhesus monkeys were born infected. All infected neonates were viable and showed signs of disease, such as low birth weights, lymphadenopathy, and rashes. Cytotoxic T-cell responses to SIV were absent in neonates, but present in mothers. The high fetal infection rate allows studies of lentiviral immunopathogenesis during ontogeny and the development of strategies to prevent maternal HIV-1 transmission. PMID- 8433277 TI - Comparative evaluation of six rapid serological tests for HIV-1 antibody. AB - Six commercial rapid test kits for HIV-1 antibody were evaluated. Four laboratory technologists tested sera from four groups of U.S. military personnel or dependents: 202 subjects positive for HIV-1 antibody by Western blot, 200 seronegative voluntary blood donors, 199 seronegative obstetrics/gynecology patients, and 99 subjects with sera reactive by ELISA but negative by recombinant protein EIA and indeterminate by Western blot. The three tests using solid-phase immunoassay technology demonstrated the highest mean sensitivity (> 99%) and specificity (> 91%) for all groups tested, including sera indeterminate by Western blot. Two dot-immunoblot assays were less specific, possibly due to indistinct reaction end points, and a latex agglutination assay was also less specific because of difficulty distinguishing reactive results from the granular background. In an "ease-of-use" assessment, solid-phase capture immunoassays required less time and equipment and were easier to interpret than other testing methods. Solid-phase capture immunoassays for HIV-1 antibody may be suitable for use in emergency situations and in developing countries because they are highly sensitive and specific and are rapidly performed with minimal laboratory equipment. PMID- 8433278 TI - Effect of zidovudine on human placental trophoblast and Hofbauer cell functions. AB - We have optimized a procedure to isolate placental trophoblasts and Hofbauer cells simultaneously in a quantity sufficient for short-term cultures and then used these placental cells to investigate the effects of zidovudine (ZDV) on trophoblast and Hofbauer cell functions. Of more than 10 term placentas tested, ZDV inhibits DNA synthesis of trophoblasts in a concentration-dependent manner with half the maximal inhibitory concentration (IC50) of 9.88 +/- 1.35 microM. Of the hormones evaluated, production of progesterone by trophoblasts is most sensitive to ZDV (IC50 = 3.65 +/- 0.29 microM). The inhibitory effect of ZDV on the secretion of placental lactogen and choriogonadotropin by the trophoblasts was detected only at a much higher concentration (> or = 60 microM). ZDV does not affect trophoblast or Hofbauer cell protein synthesis. Collectively, our results indicate that at clinically relevant concentrations (< or = 10 microM), ZDV significantly inhibits both the DNA synthesis of placental trophoblasts and their production of progesterone, while having a minimal effect on protein synthesis of both types of placental cells. PMID- 8433279 TI - T cell homeostasis in HIV infection: part of the solution, or part of the problem? PMID- 8433280 TI - HIV protease inhibitors: their anti-HIV activity and potential role in treatment. AB - Researchers are continuing to uncover important new information about the life cycle of the human immunodeficiency virus (HIV) and are further elucidating the products of the viral genome in their efforts to develop anti-retroviral therapies that are more effective and safer than those currently available. Although much attention has been focused on inhibiting proviral DNA synthesis with nucleoside analogues, other classes of agents are being explored that may enable clinicians to inhibit HIV transmission in vivo by targeting other stages of the viral life cycle. Among the novel approaches under investigation is inhibition of HIV protease, the proteolytic enzyme that is responsible for the cleavage of large precursor proteins in the budding virion. Preclinical studies indicate that protease inhibitors prevent the maturation of immature viral particles into infectious virions and thereby limit the spread of HIV in cell cultures. Laboratory data have also shown that these agents have good toxic effect profiles, and recent improvements have resulted in compounds that are more bioavailable. As phase I studies of this modality are undertaken, clinical researchers will be carefully monitoring them to determine whether these favorable in vitro characteristics of protease inhibitors will be evident in the clinical arena as well. PMID- 8433281 TI - Detection of HIV-1 provirus in bronchoalveolar lavage cells by polymerase chain reaction. AB - This study was undertaken to evaluate whether HIV-seropositive individuals harbor HIV provirus in cells obtained by bronchoalveolar lavage (BAL). BAL cells were obtained from 14 HIV-positive patients undergoing bronchoscopy for evaluation of acute pulmonary symptoms. Cells were fractionated into macrophage-enriched and lymphocyte-enriched populations. The quantity of HIV-1 proviral DNA in the unfractionated BAL cells and in each population of fractionated cells was determined following polymerase chain reaction (PCR) amplification. Detectable quantities (3-90 copies/100,000 cells) of HIV-1 proviral DNA were found in unfractionated BAL cells in 12 of 14 patients. In the other two patients, provirus was detected after a sevenfold enrichment of lymphocytes. Provirus was also detected in BAL macrophages from 8/14 patients although proviral content was significantly higher in the lymphocyte fraction (133 +/- 72 vs. 35 +/- 22 proviral copies, p = 0.03). No correlation was seen with the ability to detect provirus in lymphocyte- or macrophage-enriched fractions and clinical diagnosis (e.g., Pneumocystis carinii pneumonia). The data suggest that lymphocytes are the predominant cells that contain provirus found in the lungs, although macrophages may be infected in some patients. PMID- 8433282 TI - Decision making for clinical trials and prevention research: commentary on the model of Paltiel and Kaplan. PMID- 8433283 TI - The epidemiological and economic consequences of AIDS clinical trials. AB - The Food and Drug Administration (FDA) must manage the delicate balance between speed and safety in the evaluation and approval of new drugs. To explore how these competing obligations might be formalized with respect to the AIDS epidemic, we present a simple decision-theoretic optimization model of the clinical trials process against a backdrop of HIV transmission. Our framework sheds light on such issues as the economic consequences of decisions, the potential savings of a new therapy, the costs to society of delay, the value of better information, and how and when to undertake a clinical trial. We believe that this article represents a first effort to unravel the tangled web of epidemiological, economic, and statistical considerations that plague this policy issue. PMID- 8433284 TI - Seasonal migration: a risk factor for HIV infection in rural Senegal. AB - Sociodemographic and epidemiological data collected on a rural population of the Ziguinchor region of Senegal showed that a large part of the adult population, 80% of women between 15 and 24 years old and 82% of men between 20 and 40 years old, move each year on seasonal labor migrations to the main cities of Senegal or the Gambia or their proximity. In October 1990, an exhaustive seroprevalence survey of the population aged 20 years or older (3,230 persons tested) showed that 0.8% was HIV-2 and 0.1% HIV-1 seropositive. Interviews of 91 persons (24 seropositive persons and 67 seronegative controls) revealed that seropositivity was associated with a history of blood transfusions, injections, sexually transmitted diseases, and seasonal migration. Our findings suggest that in the rural area under study, beside a few cases of transmission by blood transfusion or injection, HIV-2 and HIV-1 are mainly transmitted first to adult men through sexual contacts with infected women met during their seasonal migration and second to their wives or regular partners once they are back home. PMID- 8433285 TI - Antibody avidity measurement and immune complex dissociation for serological diagnosis of vertically acquired HIV-1 infection. AB - Differences in avidity between HIV-1 antibodies transmitted passively and antibodies synthesized by children born to HIV-1-positive mothers can be measured using a commercially available competitive enzyme immunoassay kit. The avidity determination method is based on the competition between an anti-HIV-1-peroxidase labeled antibody at a stable and known concentration and the anti-HIV-1 antibodies (IgA, IgG, IgM) present in the child's serum at various and increasing dilutions. The shift in the competition/dilution curves between serum samples taken at the third and the sixth month of the child's life showed either the loss or the synthesis of anti-HIV-1 antibodies. The antibody avidity determination combined with a test detecting free or complexed p24 antigen is a workable and inexpensive serological method for the follow-up of children born to seropositive mothers. Combining these two complementary methods, HIV-1 infection has been established at 6 months of age in 13 of 13 infants, and positive results were confirmed by coculture and by PCR. An HIV-1 infection was excluded at 6 months of age in 17 of 17 infants, results otherwise confirmed by virological and clinical follow-up. These new and convenient approaches to the diagnosis of vertically acquired HIV-1 could be used worldwide, including in developing countries. PMID- 8433286 TI - Epidemiology of HIV infection in St. Petersburg, Russia. AB - Overall HIV-1 prevalence in St. Petersburg (Leningrad) is extremely low (0.002%). HIV-2 infection has not been detected. The possible mode of virus entry was through sexual contacts with infected foreigners, the earliest documented date being prior to 1982. Among 25 seropositive males, 18 are homosexual and five are bisexual, suggesting that the virus is circulating within resident population of homo/bisexual males. The total incidence of new infections has not shown the type of dramatic increase noted in US gay/bisexual men in early 1980s. Information on lifestyle characterization of this indigenous population require further study to determine the future potential for spread. Among the non-Soviet population the rate is 0.01%. Highest rates occur among persons from HIV endemic areas of Africa, with rates as high as 5% and 3% among persons from Uganda and Rwanda, respectively. Rates among new entrants from Africa are lower, possibly reflecting the impact of prescreening of applicants prior to arrival in Russia. Further monitoring of high-risk populations and studies to define behavior risk pattern are planned. PMID- 8433287 TI - HTLV-I-associated neurologic manifestations in four generations of a Brazilian family. AB - From an index case of tropical spastic paraparesis (TSP), four generations of a Brazilian family of African descent were investigated for human T-lymphotropic virus type I (HTLV-I) infection and its association with neurologic manifestations, as well as the possible routes of transmission. Thirty-two individuals were studied. Polymerase chain reaction (PCR) was used for confirmation of infection. HTLV-I infection was demonstrated in eight subjects (the index case, 6 of 24 blood relatives, and 1 of 7 spouses). The index case and two blood relatives had TSP, whereas subclinical neurologic disturbances were present in three other blood relatives and one spouse. Another member of the family, who had died before this study, had had diagnoses of spastic paraparesis of unknown etiology and small-cell lymphoma. Only 1 of 8 infected individuals was neurologically intact. Of 5 vertically infected individuals, 4 had been breast fed for long periods (1-2 years). These are the first reported cases of PCR proved HTLV-I-associated spastic paraparesis in Brazil. PMID- 8433288 TI - Inactivation of human immunodeficiency virus-1 at short time intervals using undiluted bleach. PMID- 8433289 TI - The hand-arm vibration syndrome--diagnosis, assessment and objective tests: a review. PMID- 8433290 TI - Amyand's hernia. PMID- 8433291 TI - The Isle-Brewers conjoined twins of 1680. PMID- 8433292 TI - Cutaneous infection caused by Mycobacterium malmoense in a patient with myelodysplastic syndrome. PMID- 8433293 TI - Liver transplantation in cystic fibrosis. PMID- 8433294 TI - Medial rectus rupture; a rare condition with an unusual presentation. PMID- 8433295 TI - Spontaneous regression of metastatic renal cell carcinoma. PMID- 8433296 TI - Opiate abuse manifesting as hyperkalaemic cardiac arrest. PMID- 8433297 TI - Hypertrophic obstructive cardiomyopathy with LEOPARD (Moynihan's) syndrome: surgical treatment. PMID- 8433298 TI - Metastatic Ewing's sarcoma of the kidney. PMID- 8433299 TI - Therapeutic success in severe iatrogenic osteoporosis in a young woman. PMID- 8433300 TI - Food sensitivity and epilepsy. PMID- 8433301 TI - Herbal teas and allergy. PMID- 8433302 TI - A first clinical trial of neural transplantation? PMID- 8433303 TI - Otitis media. PMID- 8433304 TI - Mongolian spots and GM1 gangliosidosis type one. PMID- 8433305 TI - Measurement of apolipoproteins in the diabetic clinic. PMID- 8433307 TI - An approach to breast reconstruction. PMID- 8433306 TI - Air pollution: should we be concerned about it? PMID- 8433308 TI - The role of pathology in surgery. PMID- 8433309 TI - The portrayal of the physician in non-medical literature--the physician who dislikes his trade. PMID- 8433310 TI - Genital lichen sclerosus (lichen sclerosus et atrophicus) in childhood and adolescence. PMID- 8433311 TI - Organization of day-case adenoidectomy in the management of chronic otitis media with effusion--preliminary results. AB - We report our initial findings of adenoidectomy performed in Leicester as a day case on 149 children between the ages of 3 and 9 years, who have been assessed for suitability for day-case surgery according to specific medical and social criteria. The selection a paediatric community nurse. All of the surgical procedures have been performed by experienced medical staff and the various anaesthetic techniques used by consultants or senior registrars have been documented. Six children were admitted postoperatively for overnight observation, three of whom had suffered a primary haemorrhage. No patients have been returned to theatre because of haemorrhage and there have been no re-admissions after discharge. A strict entry protocol has been observed to ensure the safety of this type of surgery and to date the acceptability of such a scheme and its organization has been widespread amongst those children and their parents who have participated. PMID- 8433312 TI - Evaluating the breast screening programme: the need for surgical audit. AB - It is to be anticipated that a reduction in population mortality attributable to mammographic screening would be heralded by an increasing proportion of breast cancer cases diagnosed at earlier stages and by an improvement in case fatality. Few cancer registers routinely produce incidence or survival data by stage at diagnosis and thus improvement in these will be the harder to assess. By thorough casenote review and follow up, this study has determined the usual presentation and survival of breast cancer in Northern Ireland in 1986 before the introduction of screening. Overall, 85% of cases were Manchester stage I or II, figures which accord with other British studies. Five-year survival ranged from 77.8% for stage I (95% confidence limits 71.7%, 82.7%) to 35.7% for stage IV (95% confidence limits 13.0%, 59.4%). Forty-three per cent of cases treated in non-teaching hospitals could not be pathologically staged, more than twice the figure for teaching hospitals (Chi-squared = 15.7, df = 1, P < 0.001). Since many tumours not detected by screening will be treated outside teaching centres, this difference will reduce the statistical power to detect the true shift in stage distribution and improvement in survival from screening. Comprehensive surgical audit would help to resolve the inadequacies in existing data collection and improve the ability to evaluate the outcome of the screening programme. PMID- 8433313 TI - Trends in urban violence: a comparison of accident department and police records. AB - Police crime statistics and crime survey data are known to be poor indicators of levels of violence in society. Longitudinal investigations of assault injury have not been carried out in accident and emergency departments hitherto, but may provide an accurate perspective of trends in violence. The attendance of assault patients at a city centre accident and emergency department was compared with 'wounding against the person' recorded by the police between 1973 and 1990. Woundings recorded by the police increased consistently throughout the study period whereas the number of assault patients did not increase between 1977 and 1987. From 1975 to 1990, police statistics showed a 9-fold and accident and emergency data a 6-fold increase. Both data sets showed substantial overall increases in violence after 1987, and a decrease in 1979. Further epidemiological studies of violence are necessary. PMID- 8433314 TI - Assault as a public health problem: discussion paper. AB - Formal collaboration between epidemiologists, A & E doctors, family practitioners, criminologists and the police is necessary so that criminal justice and public health approaches to the causes and prevention of interpersonal violence can be co-ordinated. Computerized record keeping in A & E departments, incorporating programmes dedicated to assaultive and accidental injury, is an important starting point and this needs to be organized in a systematic way so that comparisons with data collected by police and in national crime surveys can be made. Research is necessary to identify risk groups and to draw causal inferences. Criminal injury is an increasing cause of temporary and permanent handicap and death in many countries and it merits formal epidemiological research, funded by national and international health agencies. This should include the evaluation of primary and secondary prevention programmes in A & E departments and in the community. On the 10th anniversary of the publication of the Black report on inequalities in health, it is apposite to consider that high rates of intentional injury as well as illness are closely linked to poverty and that violence leaves permanent physical and psychological scars. A deprived young urban male may suffer 60 years of incapacity as a result of injury and subsequent further reductions in quality of life and self-esteem. In comparison with child abuse, the causes, identification, prevention and management of assault involving adults are not yet established as a community health issue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433315 TI - Music and Alzheimer's disease--assessment and therapy: discussion paper. PMID- 8433316 TI - Implications of selection and hybridization studies on the mode of inheritance of photoperiodically induced developmental diapause in laboratory strains of the lone star tick (Acari: Ixodidae). AB - Selection of lone star ticks, Amblyomma americanum (L.), that were reared in the laboratory under short-day photoperiods of 10:14 (L:D) h resulted in third generation (F3) diapause versus F3 nondiapause strain replete nymphs having significantly different mean molting times (days from detachment to ecdysis) of 100.9 versus 54.7 d, respectively; whereas, the F7 unselected laboratory control strain had an even smaller, significantly different mean molting time of 49.5 d. Two hybrid crosses of F2 nondiapause male with F2 diapause female ticks and F2 nondiapause female with F2 diapause male ticks yielded intermediate replete nymphal mean molting times of 62.0 and 68.9 d, respectively. All strains retained the ability to develop rapidly under long-day photoperiodic conditions of 14:10 (L:D) h, although F3 nondiapause strain ticks also exhibited reduced fitness, especially when exposed to the long-day stimuli. Analyses of molting times used as phenotypic values indicate that this diapause trait is incompletely dominant, and these and other observations indicate that inheritance of photoperiodically induced prolonged replete nymphal molting times is polygenic in this species. PMID- 8433317 TI - Reduction of nymphal Ixodes dammini (Acari: Ixodidae) in a residential suburban landscape by area application of insecticides. AB - Seven formulations of three commercially available insecticides were evaluated for their ability to reduce the density of nymphal deer ticks (Ixodes dammini Spielman, Clifford, Piesman & Corwin) in a suburban residential area endemic for Lyme disease. In total, 101 residential properties in Mount Kisco, Westchester County, NY, were treated with one of the following: carbaryl emulsifiable concentrate (EC) at 0.6 or 1.1 kg AI/ha, carbaryl granular (GR) at 4.5 kg AI/ha, chlorpyrifos wettable powder (WP) at 0.6 or 1.1 kg AI/ha, chlorpyrifos GR at 1.1 kg AI/ha, or cyfluthrin EC at 0.1 kg AI/ha. All three chemicals were found to reduce the density of nymphs on treated properties significantly compared with untreated controls. Percentage of reduction of nymphs ranged from 67.9% for carbaryl EC 1.1 kg AI/ha to 97.4% for chlorpyrifos WP 1.1 kg AI/ha. There was no difference in the amount of reduction provided by each formulation of the same chemical, but carbaryl formulations were significantly less effective than chlorpyrifos or cyfluthrin. Nymphal densities after treatment remained low throughout the course of the study, indicating that a single well-timed spring application is sufficient to provide significant reduction of nymphs for an entire transmission season. PMID- 8433318 TI - Ecological studies on the brown dog tick Rhipicephalus sanguineus (Acari: Ixodidae) in southern Israel and its relationship to spotted fever group rickettsiae. AB - An outbreak of spotted fever group rickettsiae (SFGR) was investigated by studying free-living and parasitic stages of ticks in two settlements of equal size and population located 20 km apart in the Negev Desert. Although high morbidity from SFGR was found in one of the settlements (Kibbutz Ze'elim), no clinical cases were observed in the second (Kibbutz Re'im). Using flagging and CO2-trapping, approximately 9 times more ticks were collected in Ze'elim than in Re'im. Rhipicephalus sanguineus (Latreille) was the dominant species in Ze'elim, whereas in Re'im R. turanicus Pomerantzev was the most abundant species. Several physical factors that may account for these differences were investigated. Significantly higher maximum soil temperature as well as ambient temperature above the soil were found in Ze'elim. Differences in soil composition in the two sites were also observed. Tick numbers were especially high during April through October in Ze'elim, whereas in Re'im, ticks were found mainly from April to July. A significant positive correlation was found between temperature and tick population size in Ze'elim. Dogs, sheep, goats, Mus musculus, and Meriones crassus, were more heavily infested with ticks in Ze'elim than in Re'im. The percentage of mice and dogs seropositive to SFGR was the same in both sites. In Ze'elim, 7.1% of dog owners acquired Mediterranean spotted fever during the period 1984-1989 compared with only 1.4% of people without dogs. PMID- 8433319 TI - Sex ratio and phoretic mites of fleas (Siphonaptera: Pulicidae and Hystrichopsyllidae) on the Nile grass rat (Arvicanthis niloticus) in Kenya. AB - The sex ratio of fleas and their phoretic mites associated with the Nile grass rat, Arvicanthis niloticus (Desmarest), were studied during 14 mo in a grassland community of Lake Nakuru National Park, Kenya. Females of the fleas Dinopsyllus lypusus Jordan & Rothschild, Ctenophthalmus calceatus cabirus Jordan & Rothschild, and Xenopsylla cheopis bantorum Jordan infested more grass rats and in greater numbers than did males. Phoretic hypopi (hetermorphic deutonymphs) of two species of mites, Psylloglyphus uilenbergi Fain and Paraceroglyphus xenopsylla Fain & Schwan, varied seasonally in their abundance on fleas and utilized female fleas over male fleas for their major source of transport. Additionally, the mites were very host specific with nearly 100% of those identified on D. lypusus and C. calceatus cabirus being P. uilenbergi and 89% of the mites identified on X. cheopis bantorum being P. xenopsylla. This level of specificity suggests that these mite-flea associations are highly evolved. The importance of female fleas as hosts for transporting mites also suggests that female-biased sex ratios of fleas on their hosts may be caused, in part, by females being more important as dispersers within flea populations. PMID- 8433320 TI - Experiments on the relationship between feeding of the tick Amblyomma variegatum (Acari: Ixodidae) and dermatophilosis skin disease in sheep. AB - Experiments on the systemic effect of feeding adult Amblyomma variegatum (F.) on dermatophilosis caused by Dermatophilus congolenis in six sheep were performed by feeding ticks at sites separate from sites of experimental infection with D. congolensis. Comparisons were made with D. congolensis infections on six control sheep without ticks. Tick-infested sheep developed chronic dermatophilosis lesions; tick-free sheep healed rapidly. On two tick-infested and two control sheep a chronological sequence of D. congolensis infection sites were made for histological comparisons. Dermatophilosis lesions on tick-infested sheep were characterized by chronic cellular infiltration and accumulation of plasma cells. Lesions on control sheep healed in association with transient cellular infiltration including plasma cells. In neither test nor control sheep was there evidence of effective phagocytosis of D. congolensis. It was concluded that feeding of these ticks had a systemic effect on the host such that dermatophilosis was aggravated via an effect on immunological reactions in the skin. Control of dermatophilosis by tick control is advocated. PMID- 8433321 TI - Reduced abundance of immature Ixodes dammini (Acari: Ixodidae) following incremental removal of deer. AB - The abundance of immature Ixodes dammini Spielman, Clifford, Piesman & Corwin was monitored for 9 yr (1983-1991) before and during the controlled, limited hunting of white-tailed deer, Odocoileus virginianus (Zimmerman), at a coastal Massachusetts site. Deer abundance was reduced from an estimated 350 during 1985 to approximately 60 during 1991. Although annual fluctuations were large, mean larval I. dammini abundance declined from 20.8 per white-footed mouse, Peromyscus leucopus (Rafinesque), during 1983-1986 before deer reduction to 10.3 per mouse following deer reduction (1987-1991). Similarly, mean nymphal I. dammini abundance declined from 2.7 per mouse before intervention to 1.6 per mouse after intervention. Immature I. dammini population fluctuations were not associated with those of P. leucopus. The total population of larvae infesting P. leucopus declined from 3,596 ticks before intervention to 1,535 ticks after intervention. Concurrently, the total nymphal population declined from 417 ticks before intervention to 187 ticks after intervention. The number of feeding adult female I. dammini on deer increased as deer density decreased. PMID- 8433322 TI - Effect of temperature on the transmission of western equine encephalomyelitis and St. Louis encephalitis viruses by Culex tarsalis (Diptera: Culicidae). AB - The extrinsic incubation rate (inverse of the time in days from infection to median transmission) of western equine encephalomyelitis (WEE) and St. Louis encephalitis (SLE) viruses by laboratory strains of Culex tarsalis Coquillett increased as a linear function of incubation temperatures from 10 to 30 degrees C. The estimated temperatures for zero transmission thresholds (intercept of the X axis) were 10.9 and 14.9 degrees C, and the number of degree days above these thresholds required for median transmission (inverse of the slope) was 67.6 and 115.2, respectively. Although the bodies of most Cx. tarsalis females remained infected and the WEE viral titer did not decrease significantly throughout the incubation periods at all temperatures, transmission rates by females incubated at 20 to 30 degrees C decreased markedly after peaking at 7-10 d after infection. In contrast, midgut escape and salivary gland infection barriers limited the transmission rates of SLE virus at all temperatures, but these rates did not decrease markedly as a function of incubation time, indicating that virus modulation did not occur. Degree-day models were used to calculate monthly changes in the duration of the extrinsic incubation period for WEE and SLE viruses in the San Joaquin and Coachella valleys based on mosquito temperatures estimated by combining nocturnal air and diurnal resting site temperatures. Temperatures in the San Joaquin Valley averaged 5 degrees C cooler than in the Coachella Valley, proportionately shortening the duration of the potential transmission season for WEE virus from 10 to 8 mo and for SLE virus from 8 to 5 mo, respectively. PMID- 8433323 TI - Systematic review of genera and subgenera of Rhopalopsyllinae (Siphonaptera: Rhopalopsyllidae) by phenetic and cladistic methods. AB - A systematic review of genera and subgenera of Siphonaptera Rhopalopsyllinae comprising nine operating taxonomic units is presented based on phenetic and cladistic analysis. Twenty-seven characters of adults were analyzed and the character states were determined for each character by the out-group method. Phenogram and cladograms indicated two tribes, each with two subtribes. Systematic changes proposed as a result of this study include the raising of the subgeneric status of Gephyropsylla, Hechteilla, and Ayeshaepsylla to independent genera; the recognition of a new genus, Neotropsylla, to include Polygenis guimaraesi Linardi; the division of the genus Polygenis Jordan into two subgenera: Neopolygenis subgen. n., to include species of the atopus group, and Polygenis s. str., for remaining species. PMID- 8433324 TI - Canine exposure to Borrelia burgdorferi and prevalence of Ixodes dammini (Acari: Ixodidae) on deer as a measure of Lyme disease risk in the northeastern United States. AB - Surveillance programs that identify areas where both the vector (Ixodes dammini) and etiologic agent (Borrelia burgdorferi) are present may identify the risk of Lyme disease and its spread earlier and more accurately than do programs relying on any single method, particularly human case reports. Hunter-killed deer (n = 1,204) from 22 counties in Maryland, Massachusetts, New Hampshire, New York, and Pennsylvania were examined in fall 1989 and all ectoparasites were identified. The following spring, canine sera (n = 884) were obtained from these sites, which included known endemic areas and those where Lyme disease is uncommon, and tested by enzyme-linked immunosorbent assay. Regression analysis of canine seroprevalence versus tick prevalence on deer from the same counties demonstrate a significant positive linear relationship. Sites were designated as low-, moderate-, or high-risk counties based upon their position on the regression curve. The geographic distribution of the sites correlated well with the distribution of known Lyme disease endemic and nonendemic areas. Locations were also identified where Lyme disease may be emerging. The positive relationship between measures of vector and pathogen abundance determined in this study permits public health workers to identify endemic and potentially endemic areas independently of human case reports. PMID- 8433325 TI - Formation and composition of the peritrophic membrane in the sand fly, Phlebotomus perniciosus (Diptera: Psychodidae). AB - The secretion, morphology, and chemical composition of the peritrophic membrane was studied in the sand fly, Phlebotomus perniciosus Newstead. The membrane was secreted from the entire midgut epithelium. An electron-dense fine granular secretion, possibly chitin, was present along the length of the microvilli immediately until 24 h after feeding. From 12-48 h, an electron-lucid coarse granular component, possibly protein, was also secreted from the microvillar surface. By light microscopy, the mature 36-h membrane characteristically consisted of a dark anterior cap and posterior open ring, with a transparent intervening membrane and anterior plug. Ultrastructure of the fully formed membrane at 24-48 h was highly variable. Undifferentiated membranes appeared as a single electron-lucid layer; differentiated membranes were more complex, sometimes two-layered, containing electron-lucid and -dense fibers and granules. Results of binding to succinylated wheat germ agglutinin, histochemistry, and amino acid analysis indicated that the membrane was composed of chitin, glycoprotein, and protein. Eighteen amino acids were identified in membrane proteins; aspartic-glutamic acids (and amides), serine, glycine, and lysine (45% by weight) may be important in cross-linking membrane components. PMID- 8433326 TI - Standard system for infecting ticks (Acari: Ixodidae) with the Lyme disease spirochete, Borrelia burgdorferi. AB - A standard system for infecting ticks with the Lyme disease spirochete Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner is defined. Rodents infected via tick feeding or inoculation of tick homogenates were more infectious to ticks than rodents infected with culture-derived spirochetes. White laboratory mice were more infectious than hamsters. Three strains of B. burgdorferi (JD1, B31, and WI210) produced batches of infected ticks with > 80% infection when mice were infected with tick-derived material. Ixodes dammini Spielman, Clifford, Piesman & Corwin were 3.6x more efficient than I. pacificus Cooley & Kohls in acquiring and maintaining infection with two California strains of B. burgdorferi, originally isolated from I. pacificus. PMID- 8433327 TI - Plague (Yersinia pestis) in cats: description of experimentally induced disease. AB - Sixteen healthy cats were fed a 6-wk-old laboratory mouse that had died of experimentally induced Yersinia pestis infection (strain NM77-538), to simulate oral exposure to plague. The cats were closely monitored after ingestion. Physical exams were performed and vital signs were recorded daily. Plague antibody titers and cultures of blood, throat, and oral cavity were performed daily. Complete blood counts and biochemistry panels were performed every 3 d. Complete necropsies were performed on any cats that died. Cats exhibited one of three responses following ingestion of one plague-infected mouse; they either died (6/16 or 38%), developed transient illness and recovered (7/16 or 44%) or showed no signs of illness (3/16 or 19%). A continual fever greater > 40 degrees C was associated with a poor prognosis. The highest antibody titers developed in the group that shed the plague bacillus over an extended period of time. Blood, throat, and oral cavity cultures were positive in 100% of the fatal cases. Throat cultures were positive in 75% of the exposed cats. In contrast to other carnivores, cats infected with Y. pestis exhibit bubo formation and pneumonic lesions similar to those seen in people with plague. Because of the potential transmission of Y. pestis from cats to people, development of a plague vaccine for cats may be warranted. PMID- 8433328 TI - Effect of Yersinia pestis infection on temperature preference and movement of the Oriental rat flea (Xenopsylla cheopis) (Siphonaptera: Pulicidae). AB - Previous laboratory studies have shown that inoculation of bacterial endotoxin into the hemocoel of some arthropods, or natural infection by a number of pathogens, causes them to seek out a higher ambient temperature. This phenomenon has been called behavioral fever. Yersinia pestis is an endotoxin-producing bacterium that relies on infection of fleas for transmission. Behavioral fever in fleas might enhance the transmission of plague if infected fleas were induced to seek out a warm-bodied host after the death of an infected host. Our study indicates that in thermal gradient Y. pestis infected Oriental rat fleas (Xenopsylla cheopis) do not exhibit behavioral fever and in one experiment sought out a significantly lower temperature. PMID- 8433329 TI - Reservoir competence of white-footed mice for Babesia microti. AB - Although the white-footed mouse, Peromyscus leucopus Rafinesque, has been incriminated as the main reservoir of the agent of human babesiosis, Babesia microti Franca, a quantitative demonstration of reservoir competence has not been presented. Mice captured within an intensely zoonotic site served as host for laboratory-reared larval Ixodes dammini Spielman, Clifford, Piesman, and Corwin, and the resulting nymphal ticks were assayed for evidence of salivary gland infection by the piroplasm. Solely 25% of the mice were patently parasitemic on thin blood smears, but virtually all mice infected ticks with B. microti. Thus, smear positivity correlates poorly with infectivity. Infection in smear-negative mice, however, was demonstrated by the use of the polymerase chain reaction. White-footed mice may be chronically infected by the piroplasm with parasitemias detectable only by the most sensitive methods, yet efficiently serve as a source of infection. We conclude that P. leucopus serves to maintain B. microti in the northeastern United States, as it does the spirochetal agent of Lyme disease. PMID- 8433330 TI - Polymerase chain reaction approaches to Culicoides (Diptera: Ceratopogonidae) identification. AB - Molecular genetic approaches such as polymerase chain amplification (PCR) of target genomic sequences are finding wide application in systematic and taxonomic studies of arthropods. PCR-based techniques that preclude the need for target DNA sequence information of the species of interest facilitate molecular taxonomic studies. Two such techniques, tDNA-PCR (DNA encoding tRNAs is the analyte) and RAPD-PCR (randomly amplified polymorphic DNA) were investigated for their ability to differentiate certain North American Culicoides spp. larvae and adults. PMID- 8433331 TI - Susceptibility parameters of Aedes albopictus to per oral infection with eastern equine encephalitis virus. AB - Aedes albopictus (Skuse) mosquitoes were fed on snowy egrets, Egretta thula (Thayer and Bangs), that had been infected by subcutaneous inoculation of eastern equine encephalitis (EEE) virus. Freshly fed mosquitoes were frozen and tested to determine how much virus they had ingested. Other fed mosquitoes from the same lots were incubated for 7 d at 27 degrees C before testing. Seven lots of Ae. albopictus fed on viremic birds. Based on average amounts of virus ingested and day 7 virus infection rates in mosquitoes from the same lots, the amount of virus required to infect 50% of the mosquitoes was calculated to be 10(2.8) Vero cell plaque-forming units (PFU). The infection threshold (i.e., the amount of virus required to infect from 1 to 5% of mosquitoes) was determined to be < or = 10 PFU per blood meal. These parameters indicate that Ae. albopictus is sufficiently susceptible to infection with EEE virus to enable it to acquire infectious doses from a wide variety of viremic birds and possibly from equines. PMID- 8433333 TI - Notes on the geographical distribution and host preferences in the order Siphonaptera. Part 8. New taxa described between 1984 and 1990, with a current classification of the order. AB - An inventory of all new taxa erected in the order Siphonaptera between 1 January 1984 and 31 December 1990 is presented. This includes one subfamily, five tribes, one genus, five subgenera, and 158 species and subspecies. Taxon accounts include the names of authors and publication sources, as well as collection data. Where known, the depository of the primary type is also included. An extensive bibliography is given as well as an updated supraspecific classification for the entire order based on studies published during the last decade. PMID- 8433332 TI - Ecology of porcupines (Erethizon dorsatum) and Colorado tick fever virus in Rocky Mountain National Park, 1975-1977. AB - The involvement of porcupines, Erethizon dorsatum (L.), in the ecology of Colorado tick fever (CTF) virus in Rocky Mountain National Park was investigated from 1975 to 1977. Porcupine dens and feeding activity were found mostly on rocky knolls or on south-facing slopes within open stands of the montane coniferous forest, and 20 adult porcupines were trapped or captured by hand at those locations. An average of 24.6 +/- 5.4 adult Dermacentor andersoni Stiles ticks were found per animal (annual range, 17.5-31.4 ticks). The minimum CTF virus infection rate of the ticks removed from porcupines varied from 129 to 257, whereas for questing adult D. andersoni ticks from the same geographic area was 205 in 1976. No virus was isolated from the 20 animals, but 85% had neutralizing antibody against CTF virus. Porcupines utilize the same habitats described for the CTF ecosystem in Rocky Mountain National Park and appear to be an important host for adult D. andersoni. PMID- 8433334 TI - Arbovirus surveillance in northern Colorado, 1987 and 1991. AB - Arbovirus surveillance was conducted during an epizootic of western equine encephalitis (WEE) during 1987 and during a nonepizootic year, 1991, in the same area in northern Colorado. Mosquitoes were collected in Larimer County, CO, during weeks 33-37 (10 August to 7 September) in 1987 and during weeks 26-35 (24 June to 26 August) in 1991. In total, 13,099 mosquitoes in 694 pools collected during 1987 and 8,672 mosquitoes in 242 pools collected during 1991 were tested for virus. WEE virus was isolated in both years from Culex tarsalis Coquillett and from Cx. pipiens L. in 1987. Infection rates and population levels of Cx. tarsalis were not significantly different in the 2 yr during weeks 33, 34, and 35 (12-26 August). St. Louis encephalitis virus was isolated in 1987 from Cx. tarsalis. Other viruses isolated included Hart Park, Turlock, and Jerry Slough, a variety of Jamestown Canyon virus. PMID- 8433335 TI - Differential recognition of saliva antigens from the ixodid tick Amblyomma hebraeum (Acari: Ixodidae) by sera from infested and immunized rabbits. AB - We determined the protein composition and antigenic content of saliva from Amblyomma hebraeum female ticks of different weight classes. The mean protein concentration of saliva of small partially fed ticks (< 100 mg) was 333 +/- 83 micrograms/ml and that of large partially fed ticks (150-420 mg) was 59 +/- 14 micrograms/ml. The reduction in concentration mostly was caused by the significantly higher fluid volume per minute secreted by large ticks. Polypeptide analysis of saliva indicated the presence of a protein (14 kilodaltons [kD]) only in ticks weighing < 60 mg. Other saliva proteins of 21 and 26 kD were present only in ticks weighing < 150 mg, whereas 68-kD protein was absent or very faint in ticks > 100 mg. Immunoblot analysis indicated that sera from rabbits infested with ticks recognized 13 saliva antigens ranging in size from 23 to 200 kD. The antigens were present in detectable quantities in the saliva of small ticks only. In contrast, the sera from rabbits immunized with tick saliva recognized only four antigens from 63 to 200 kD. The 63-kD antigen was not present in the saliva of large ticks. These data indicate that the saliva of A. hebraeum from small ticks is antigenically more complex than that of large ticks and that the route of immunization influences the humoral immune response of the host to the saliva antigens. PMID- 8433336 TI - Host-feeding patterns of Aedes albopictus (Diptera: Culicidae) at a temperate North American site. AB - Precipitin tests and ELISA were used to investigate host-feeding patterns of 172 blood-fed Aedes albopictus (Skuse) collected at Potosi, MO, during the summers of 1989 and 1990. One hundred ten (64.0%) mosquitoes had fed on mammals, 29 (16.9%) on birds, and none on turtles or snakes. Thirty-three (19.2%) mosquitoes failed to react in all tests. Eighty-six (78.2%) of the 110 mammalian feeds were positive for lower taxa as follows: rabbit, 24.5%; deer, 14.5%; dog, 13.6%; human, 8.2%; squirrel, 7.3%; opossum, 4.5%; myomorph rodents other than Rattus, 3.6%; raccoon, 0.9%; and bovine, 0.9%. Positive feeds were not detected for the following mammals: cat (n = 99); horse (n = 95); Rattus (n = 84); and swine (n = 84). Fourteen (48.3%) of the 29 avian feeds were positive for lower taxa as follows: Passeriformes, 24.1%; Columbiformes, 17.2%; Ciconiiformes, 3.4%; and quail, 3.4%. These data, the first on host-feeding patterns for Ae. albopictus populations in the New World, indicate that Ae. albopictus is an opportunistic feeder that utilizes a wide variety of hosts and, therefore, has the potential to become involved in the transmission cycles of indigenous arboviruses. PMID- 8433337 TI - Maintenance by hares of European Borrelia burgdorferi in ecosystems without rodents. AB - During May-October 1991 shrews (Sorex spp.), small rodents (Apodemus spp., Clethrionomys glareolus [Schreber]), and hares (Lepus spp.) were sampled near Stockholm, Sweden. Nymphal Ixodes ricinus (L.) derived from blood-engorged larvae collected from these mammals were investigated by phase-contrast microscopy and immunofluorescence assay (IFA) using the monoclonal antibody H6831 directed against the OspB protein of Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner. Three rodent species, previously known as vertebrate reservoirs for B. burgdorferi in Switzerland, are competent reservoirs of Lyme borreliosis also in Sweden. The first data are presented showing Lyme disease reservoir competency of European insectivores (Sorex araneus L., S. minutus L.) and lagomorphs (Lepus europaeus Pallas, L. timidus L.). Lagomorphs are the only European vertebrates known to be both competent reservoirs for B. burgdorferi and a source of blood for all stages of I. ricinus. We propose that Lyme borreliosis can be maintained for prolonged periods on islands, without rodents and insectivores, if lagomorphs are present; and, in such ecosystems, fluctuations of lagomorph population levels may influence the numbers of B. burgdorferi-infected ticks and hence the risk of human Lyme disease infection. PMID- 8433338 TI - Occurrence and distribution in Rhode Island of Hunterellus hookeri (Hymenoptera: Encyrtidae), a wasp parasitoid of Ixodes dammini. AB - The wasp Hunterellus hookeri Howard parasitizes several species of ixodid ticks including Ixodes dammini Spielman, Clifford, Piesman & Corwin, the vector of Lyme disease spirochetes, Borrelia burgdorferi, in the northeastern United States. We detected the occurrence and evaluated the distribution of this wasp parasitoid in populations of I. dammini in Rhode Island. There has been no intentional introduction of a tick parasitoid recorded anywhere in Rhode Island; yet, we found this wasp at one of the six study sites (Prudence Island), where it parasitized 21 (n = 243) and 17% (n = 284) of nymphal I. dammini collected during 1988 and 1989, respectively. The proportion of nymphs parasitized was greatest during May (46%) and was less in June (18%), July (18%), and August (11%). In Rhode Island, the wasp was only found parasitizing ticks at the site with the highest (by a factor of 2) tick population, confirming similar observations in Massachusetts and New York. It is suggested that establishment as well as the distribution of H. hookeri depends upon a super abundant deer tick population. The usefulness of this parasitoid as a biological control agent is yet unknown. PMID- 8433339 TI - Laboratory transmission of eastern equine encephalomyelitis virus to chickens by chicken mites (Acari: Dermanyssidae). AB - Pools of adult female chicken mites, Dermanyssus gallinae (De Geer), were allowed to feed on chicks that had been inoculated with eastern equine encephalomyelitis (EEE) virus and that had a viremia level of 10(6.2)-10(6.6) plaque-forming units per milliliter of blood. Virus remained detectable by plaque assay in samples of these mites for 30 d after the infectious blood meal. Virus was not recovered from any of 151 progeny of virus-exposed female mites. Mites that had fed on viremic chicks were allowed to feed on naive chicks 3, 7, 11, 15, or 30 d later. EEE virus was transmitted to chicks by these mites on days 3 (one transmission in four trials) and 7 (one transmission in four trials). Both transmissions were confirmed by the presence of virus in chick blood 24-72 h after mites had fed, and by plaque-reduction neutralization assays of 21-d convalescent chick sera against the original viral strain. PMID- 8433340 TI - Effects of temperature on fecundity and viral replication in Amblyomma cajennense (Arachnida: Ixodidae) infected with Venezuelan equine encephalomyelitis virus. AB - To assess how temperature affects fecundity and Venezuelan equine encephalomyelitis (VEE) viral replication in VEE-infected Amblyomma cajennense (F.), adult ticks were inoculated intracoelomically with either VEE virus (I-A variant) or diluent. Ticks were held at 19, 26, or 33 degrees C and tested for VEE virus over 20 d. Up to 10 pairs of ticks (1 female:1 male) from each temperature group were allowed to feed on guinea pigs on day 8 after inoculation. Maximum titers did not differ significantly among infected ticks held at 19, 26, or 330 degrees C (P = 0.59), and ticks maintained high viral titers throughout the sampling period. Likewise, there was no significant difference in the number of eggs oviposited between ticks inoculated with virus or diluent and held at the same temperature, or among groups held at different temperatures (P = 0.48). The percentage of viable eggs from virus-inoculated or diluent-inoculated adults also was not significantly different (P > or = 0.14). PMID- 8433341 TI - Fleas (Siphonaptera) infesting giant kangaroo rats (Dipodomys ingens) on the Elkhorn and Carrizo Plains, San Luis Obispo County, California. AB - The giant kangaroo rat, Dipodomys ingens (Merriam), has a limited distribution in the San Joaquin Valley, CA. Because of reductions in its geographic range, largely resulting from humans, the species was listed as an endangered species in 1980 by the California Fish and Game Commission. As part of a study of the community ecology of southern California endangered species, including D. ingens, we were able to make flea collections from the rats when they were trapped and marked for population studies. All but one of the fleas collected from the D. ingens in this study were Hoplopsyllus anomalus, a flea normally associated with ground squirrels (Sciuridae). It has been suggested that giant kangaroo rats fill the ground squirrel niche within their range. Our data indicate that this role includes a normal association with Hoplopsyllus anomalus. PMID- 8433342 TI - Efficient transmission of tick-borne encephalitis virus between cofeeding ticks. AB - Most of the data on oral infections of ticks with tick-borne encephalitis virus have been derived from experiments using animals infected by syringe inoculation. To mimic the natural conditions of virus transmission, tick-borne encephalitis virus-infected Ixodes ricinus (Linnaeus) or Rhipicephalus appendiculatus Neumann adults (donors) were cofed with uninfected nymphs (recipients) of either tick species on uninfected guinea pigs. Two tick-retaining cells were attached to each guinea pig: cell 1 contained uninfected nymphs and virus-infected adults, and cell 2 contained uninfected nymphs. Following engorgement, 55% of I. ricinus nymphs and 65% of R. appendiculatus nymphs were shown to have acquired the virus while cofeeding with I. ricinus donor ticks. Similarly, 66% of R. appendiculatus recipient nymphs that cofed with R. appendiculatus virus-infected adults were infected. Some of the guinea pigs on which the ticks cofed were apparently nonviremic. The results indicate that efficient transmission of tick-borne encephalitis virus can occur between cofeeding ticks even when the host on which they feed does not develop a detectable viremia. PMID- 8433343 TI - Allan Marion Barnes: an overview of his life and a selected bibliography. PMID- 8433344 TI - Review of the species of Rallicola (Phthiraptera: Philopteridae) from the woodcreepers (Passeriformes: Dendrocolaptinae). AB - Sixteen species of chewing lice in the genus Rallicola are recognized and described from members of the passerine subfamily Dendrocolaptinae. These include 12 previously described species and 4 new ones: R. keymerae from Dendrocolaptes picumnus, R. lyali from Xiphocolaptes major, R. harveyi from Deconychura longicauda, and R. palmai from Campylorhamphus trochilirostris. New synonymies include R. guttata and R. pyriglena, both of which are junior synonyms of R. chunchotambo, and R. certhia microgenitalia, which is a junior synonym of R. colombiana. A key is provided for identification of the species treated herein. PMID- 8433345 TI - Distribution and seasonal and diurnal activity patterns of Eutrombicula alfreddugesi (Acari: Trombiculidae) in a forest edge ecosystem. AB - Microclimatic and vegetative effects on the population size and activity patterns of larval Eutrombicula alfreddugesi Oudemans, 1910 (Acari: Trombiculidae), were investigated in Nebraska between latitude 40 degrees 0'0" N and 40 degrees 1'21" N. Larval population densities along a forest edge were greatest in areas of high relative humidity, moderate temperature, low incident sunlight, and increasing substrate vegetation. Although chigger populations existed throughout the forest edge, larger populations concentrated in short- to tall-grass transition zones. Chiggers were rarely found in the undergrowth beneath the tree canopy. Chigger activity correlated with a microclimatically driven diurnal rhythm. Activity was greatest during the late afternoon-early evening, between 1530 and 1930 hours (CDST). Larval activity dropped to low levels and remained so until sunrise; this period of reduced activity occurred between 1930 and 0530 hours. Small increases in larval activity occurred around sunrise (approximately 0600-0700 hours). Between about 0700 and 1530 hours, larval E. alfreddugesi were inactive and did not respond to normal sampling stimuli. Larval populations appeared in late April through early May, peaked in abundance in late June and early July, diminished through late summer, and disappeared in midautumn as the ground began to freeze. PMID- 8433346 TI - Conspecificity of the ticks Ixodes scapularis and I. dammini (Acari: Ixodidae). AB - Reciprocal crosses between Ixodes dammini Spielman, Clifford, Piesman & Corwin from Massachusetts and Ixodes scapularis Say from Georgia produced offspring through the F3 generation when the experiment was discontinued. Reciprocal I. dammini x Ixodes pacificus Cooley & Kohls (California) and I. scapularis x I. pacificus crosses produced F1 progeny; however, all progeny were sterile. Assortative mating experiments between I. dammini and I. scapularis indicated that males and females of both species mated with the opposite sex of heterospecific or conspecific ticks when there was a choice. Conventional discriminant analysis of morphometric measurements of ticks from Georgia, North Carolina, Maryland, Massachusetts, and two populations of F1 hybrids indicated that there were recognizable differences. However, size-free (sheared) discriminant analysis indicated that these differences were largely size dependent, with much overlap of the four eastern and two hybrid populations but no overlap with I. pacificus from California. Analysis of chromosomes (morphology and C band) indicated no differences between the Georgia and Massachusetts populations but showed a difference between them and the California population of I. pacificus. Analysis of isozymes showed that the genetic identity value for the Georgia and Massachusetts populations was within the normal range for conspecific populations, whereas the California population indicated congeneric but not conspecific relatedness to the Georgia and Massachusetts populations. Life cycle data collected under similar laboratory conditions showed no differences in length of feeding and molting periods among Georgia, Massachusetts, and California populations. These data and results of the work of other authors on tick host preferences and vector competence indicate that I. dammini is not a valid species separate from I. scapularis. Because the name Ixodes scapularis Say, 1821, has priority over the name Ixodes dammini Spielman, Clifford, Piesman & Corwin, 1979, I. dammini is relegated to a junior subjective synonym of I. scapularis (based on Article 23 of the International Code of Zoological Nomenclature). PMID- 8433347 TI - Checklist of the valid genus-group names in the Siphonaptera, 1758-1991. AB - A complete inventory of the 307 currently valid genus-group names in the insect order Siphonaptera is given, along with their place of publication and type species. PMID- 8433348 TI - Efficiency of transovarial transmission of the Lyme disease spirochete, Borrelia burgdorferi, in the western blacklegged tick, Ixodes pacificus (Acari: Ixodidae). AB - The efficiency of transovarial transmission of Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner was evaluated in Ixodes pacificus Cooley & Kohls collected from two areas of northern California where Lyme disease is endemic. In total, 132 (8.8%) of 1,499 replete females examined by direct immunofluorescence were demonstrated to be infected with B. burgdorferi. Larvae or eggs from 119 of these females were examined for the presence of spirochetes by direct immunofluorescence, placing them in culture, or both; none was found to contain B. burgdorferi. The fecundity of 20 midgut-infected (mean = 874.2) and 20 uninfected (mean = 1,048.3) I. pacificus females did not differ statistically. Likewise, the fertility of infected (mean = 87.0%) and uninfected (mean = 89.9%) females and the mean engorged weights of both groups (infected, 120.8 mg versus uninfected, 132.7 mg), were comparable. The fecundity, fertility, and mean weights of six replete females having ovarian infections, six females having midgut-restricted infections, and six uninfected females were also similar. We conclude that transovarial transmission is not efficient for maintaining B. burgdorferi in populations of I. pacificus, a known vector of that pathogen. Infection with the spirochete does not appear to affect either feeding or reproductive success adversely in females of this tick. PMID- 8433349 TI - Role of the eastern chipmunk as a host for immature Ixodes dammini (Acari: Ixodidae) in northwestern Illinois. AB - Infestation of the eastern chipmunk, Tamias striatus L., by immature Ixodes dammini Spielman, Clifford, Piesman and Corwin was studied in Castle Rock State Park in northwestern Illinois during June-October 1991. Mean larval density peaked in August, while nymphal density declined steadily through the study period. Prevalence of tick infestation was high throughout the trapping period. Tick distribution on chipmunks was aggregated in most of the sampling periods. Levels of I. dammini infestation recorded on chipmunks in this survey are higher than previous results recorded in the northeastern and midwestern United States. Chipmunks had significantly higher levels of nymphal I. dammini infestation than white-footed mice (Peromyscus leucopus Rafinesque). A major role of the eastern chipmunk as a host for immature I. dammini in upland forest habitat in northwestern Illinois can be established. In bottomland and ecotone habitats where chipmunks were scarce, P. leucopus contributed most to the feeding of larval ticks. PMID- 8433350 TI - Detection of multiple blood feeding in Aedes aegypti (Diptera: Culicidae) during a single gonotrophic cycle using a histologic technique. AB - We evaluated a histologic technique for its usefulness in detecting multiple blood feeding by Aedes aegypti (L.) in a single gonotrophic cycle. To standardize the procedure, we carried out a laboratory study in which 166 mosquitoes imbibed two blood meals at known intervals. Eighty percent (78/98) of the multiple meals were detected when the interval between meals was from 1 to < to = 24 h and the time from the second meal to fixation ranged from 0 to 12 hr. At intervals outside this range, only 34% (23/68) of the multiple meals were detected. Overall, 61% (101/166) of the double meals were detected. Examination of 96 engorged Ae. aegypti collected by aspiration from inside houses in San Juan, Puerto Rico, indicated that 50% had imbibed multiple meals. Most wild-caught mosquitoes took their last meal the day before capture, and most multiple feeders fed twice on consecutive days. A dark line of digested blood, or heme, around the first meal and a physical separation between meals were the most useful histologic parameters for detecting multiple feeding in wild Ae. aegypti. An association of multiple feeding with advanced stages of oocyte development suggests that, at the time of collection, most Ae. aegypti from the study site had fed twice in each gonotrophic cycle. We conclude that, although it is labor intensive, histologic examination is an appropriate technique for a longitudinal, community-wide survey of multiple feeding by Ae. aegypti. PMID- 8433351 TI - Substrate and inhibitor specificity of the lactate carrier of human neutrophils. AB - The substrate and inhibitor specificity of the lactic acid (Lac) transport system of human neutrophils was investigated. The ability of a variety of compounds to inhibit the influx of [14C]lactate, presumably reflecting competition by substrate analogues for binding at the external translocation site, was taken as an index of affinity for the Lac carrier. pH-state techniques were utilized to assess transportability. Results indicate a relatively low order of selectivity, the neutrophil H+(+)lactate- cotransport system demonstrating a broad acceptance of short-chain unsubstituted and substituted alkyl monocarboxylates as well as aromatic monocarboxylates. There was a slight preference for oxo, Cl, and OH substituents over other groups at the two-position of short chain alkyl fatty acids: all were readily transported across the plasma membrane at rates approaching that of L-lactate itself. Aromatic acids were not transported inward by the carrier although these compounds did permeate via simple nonionic diffusion. The neutrophil Lac carrier can be blocked by a number of cyanocinnamate derivatives, the classical inhibitors of monocarboxylate transport in mitochondria, and by dithiol compounds and sulfhydryl-reactive agents. This constellation of biochemical properties is similar to the features that characterize other well described H+(+)lactate- cotransport systems in red blood cells, Ehrlich ascites tumor cells, hepatocytes, and cardiac sarcolemmal vesicles, although significant differences exist when comparisons are made to the Na(+)-dependent lactate transporter of the kidney proximal tubule. PMID- 8433352 TI - Relation between cytoskeleton, hypo-osmotic treatment and volume regulation in Ehrlich ascites tumor cells. AB - Pretreatment with cytochalasin B, which is known to disrupt microfilaments, significantly inhibits regulatory volume decrease (RVD) in Ehrlich ascites tumor cells, suggesting that an intact microfilament network is a prerequisite for a normal RVD response. Colchicine, which is known to disrupt microtubules, has no significant effect on RVD. Ehrlich cells have a cortical three-dimensional, orthogonal F-actin filament network which makes the cells look completely black in light microscopy following immunogold/silver staining using anti-actin antibodies. After addition of cytochalasin B, the stained cells get lighter with black dots localized to the plasma membrane and appearance of multiple knobby protrusions at cell periphery. Also, a significant decrease in the staining of the cells is seen after 15 min of RVD in hypotonic medium. This microfilament reorganization appears during RVD in the presence of external Ca2+ or Ca(2+) ionophore A23187. It is, however, abolished in the absence of extracellular calcium, with or without prior depletion of intracellular Ca2+ stores. An effect of increased calcium influx might therefore be considered. The microfilament reorganization during RVD is abolished by the calmodulin antagonists pimozide and trifluoperazine, suggesting the involvement of calmodulin in the process. The microfilament reorganization is also prevented by addition of quinine. This quinine inhibition is overcome by addition of the K+ ionophore valinomycin. PMID- 8433353 TI - Membrane stretch activates a high-conductance K+ channel in G292 osteoblastic like cells. AB - A high-conductance K(+)-selective ion channel was studied in excised membrane patches from human G292 osteoblast-like osteosarcoma cells. Channel conductance averaged approximately 170 pS in symmetric solutions of 153 mM KCl, and approximately 135 pS when the pipette was filled with standard saline (150 mM NaCl). The probability of the channel being in an open state (Popen) increased with membrane potential, internal calcium, and applied negative pressure. At pCa7, channel activity was observed at membrane potentials greater than approximately 60 mV, while at pCa3, channel activity was seen at approximately 10 mV. Likewise, in the absence of applied pressure, channel openings were rare (Popen = 0.02), whereas with -3 cm Hg applied pressure, Popen increased to approximately 0.40. In each case, i.e., voltage, calcium concentration, and pressure, the increase in Popen resulted from a decrease in the duration of long closed (interburst) intervals and an increase in the duration of long-open (burst) intervals. Whole-cell responses were consistent with these findings. Hypotonic shock produced an increase in the amplitude and conductance of the outward macroscopic current and a decrease in its rise time, and both single channel and whole-cell currents were blocked by barium. It is suggested that the voltage-gated, calcium dependent maxi-K+ channel in G292 osteoblastic cells is sensitive to membrane stretch and may be directly involved in osmoregulation of these cells. Further, stretch sensitivity of the maxi-K+ channel in osteotrophic cells may represent an adaptation to stresses associated with mechanical loading of mineralized tissues. PMID- 8433354 TI - Affective and cognitive responses to disease detection and health promotion behaviors. AB - In this set of studies an attempt was made to distinguish between disease detection and health promotion behaviors. Disease detection behaviors were defined as behaviors designed to detect physical pathology (e.g., cholesterol check) and health promotion behaviors were defined as behaviors that may directly improve health (e.g., eating a low-fat diet). It was proposed that the decision to engage in detection behaviors is associated more with affect and that the decision to engage in promotion behaviors is associated more with cognition. Two studies were conducted to test this hypothesis. In Study 1 participants' affective and cognitive responses to five detection behaviors and five promotion behaviors were measured. Consistent with our hypothesis, detection behaviors were associated with more affective responses. Study 2 used a different procedure to measure affect and cognition and replicated the findings of Study 1. In addition, Study 2 examined how promotion and detection behaviors respond to information and emotional persuasive messages. PMID- 8433355 TI - Self-efficacy and the maintenance of exercise participation in older adults. AB - The role played by exercise self-efficacy in the maintenance of exercise participation of previously sedentary middle-aged adults 4 months after the termination of a formal exercise program is reported. Correlational and multiple regression analyses examined the influence of self-efficacy, physiological (aerobic capacity, sex, body composition), and behavioral (past exercise frequency and intensity) parameters in the maintenance of exercise participation. Self-efficacy significantly predicted exercise behavior at follow-up when controlling for biological and behavioral influences. Aerobic capacity, exercise efficacy, and exercise behavior in combination were significantly related to current energy expenditure in aerobic physical activity. The discussion focuses on the need to examine the impact of different correlates of exercise behavior at different stages of the exercise process. PMID- 8433356 TI - The relative importance of dispositional optimism and control appraisals in quality of life after coronary artery bypass surgery. AB - Similar mechanisms have been proposed to explain the stress-buffering effects of both dispositional optimism and perceived control. Yet dispositional optimism as a personal resource should function independently of situational control appraisals. To evaluate the unique and additive contributions to adaptation of control appraisals and optimism, we followed 49 individuals scheduled for coronary artery bypass surgery. One month before surgery dispositional optimism was associated with neither health locus of control nor specific expectancies about the outcomes of surgery. Dispositional optimism, however, was associated with perceived control over the course of the illness and with quality of life appraisals. Although presurgery optimism predicted life quality 8 months after surgery, this was not the case when general and specific control appraisals and specific expectancies were included in the prediction. These findings are discussed as they relate to current conceptions of trait optimism. PMID- 8433357 TI - Emotional support as a moderator of adjustment and compliance after coronary artery bypass surgery: a longitudinal study. AB - The independent relationships of emotional support and marital status with posthospital adjustments following coronary artery bypass surgery (CABS) were examined longitudinally with an intake sample of 85 male patients. Follow-ups occurred at 1, 4, and 13 months after hospital release. Demographic characteristics (age, education) and cardiac status at the time of surgery (wall motion abnormalities) were controlled statistically. As anticipated, married patients were higher in emotional support throughout the follow-up period than were their unmarried counterparts, and both groups reported decreased support with time. Of more interest, higher support was significantly and independently predictive of better emotional status (lower anxiety, depression), perceived quality of life, and compliance with recommended behaviors (ambulating and not smoking). Support did not predict cardiac health (angina episodes, doctor visits for cardiac problems) during follow-up, however. There was no evidence that marital status, independent of emotional support, was related significantly to outcomes. PMID- 8433358 TI - Cognitive distraction and relaxation training for the control of side effects due to cancer chemotherapy. AB - Sixty cancer chemotherapy patients were randomly assigned to one of six conditions formed by a 3(cognitive distraction, relaxation training, no intervention) x 2(high anxiety, low anxiety) factorial design. All patients were followed for five consecutive chemotherapy sessions. Outcome measures included patient reports, nurse observations, and physiological indices. Results indicated that distraction patients reported less nausea prior to chemotherapy and lower systolic blood pressures after chemotherapy than controls. Relaxation training patients reported less nausea prior to chemotherapy and exhibited lower systolic and diastolic blood pressures after chemotherapy than control patients. There were no significant differences between distraction and relaxation training patients on any measure. Patients with high initial levels of anxiety exhibited continually elevated levels of distress throughout the chemotherapy experience; however, anxiety level did not interact with the effectiveness of the treatment interventions. Overall, the data support the use of both cognitive distraction and relaxation training for reducing the distress of chemotherapy with both high and low-anxiety patients and suggest that at least some of the effects of relaxation training can be achieved with distraction alone. PMID- 8433359 TI - The pattern of influence of perceived behavioral control upon exercising behavior: an application of Ajzen's theory of planned behavior. AB - The aim of the present studies was to verify the basic assumptions underlying the theory of planned behavior for the prediction of exercising intentions and behavior among adults of the general population (study 1) and a group of pregnant women (study 2). In both studies, baseline data were collected at home with trained interviewers and with the use of paper-and-pencil questionnaires. The self-report on behavior was obtained 6 months (study 1) and between 8 and 9 months (study 2) after baseline data collection. In study 1, perceived behavioral control influenced behavior only through intention. In study 2, none of the Ajzen model variables was associated to exercising behavior. Nonetheless, intention was influenced by attitude, habit, and perceived behavioral control. The results of the present studies suggest that perceived behavioral control contributes to the understanding of intentions to exercise but not to the prediction of exercising behavior. PMID- 8433360 TI - Metal-induced conformational changes in transferrins. AB - Recent studies on iron-loaded transferrins have revealed a conformational change upon binding iron due to a domain closure. It has been suggested that the domain closure may be the key for the receptor recognition of the metal loaded transferrin (Grossmann et al., 1992). Small angle X-ray scattering has been used to provide direct structural information on the conformational changes that may take place upon the binding and release of different metals to the transferrins in solution. The data show that In3+ and Cu2+ induce the same domain closure as Fe3+; Al3+ causes a conformational change of somewhat smaller magnitude while Hf4+ does not induce any conformational change. The results are discussed in terms of the molecular recognition of metal loaded transferrin by the receptor. PMID- 8433361 TI - Conformation of complementarity determining region L1 loop in murine IgG lambda light chain extends the repertoire of canonical forms. AB - The refined structure of Se155-4 Fab fragment, the first murine antibody with the lambda light chain, reveals a novel conformation of the light chain complementarity determining region L1. This conformation extends the repertoire of canonical structures. The main determinant of this conformation is the packing of the Val27c side-chain into a hydrophobic pocket formed by the side-chains of Ala33, Leu66, Ala71 and Leu90. The framework L-FR3 loop, encompassing residues 66 to 72, which packs next to the L1 loop, bends significantly more toward the exterior of the molecule than in other Fab fragments. Sequence analysis suggests that the conformations of the L1 and L-FR3 loops observed in Se155-4 are adopted by a majority of murine lambda light chains. PMID- 8433362 TI - Non-random distribution of amino acids in the transmembrane segments of human type I single span membrane proteins. AB - The distribution of amino acids in the transmembrane segments and flanking regions of 115 human type I single span (amino terminus extracellular and carboxyl terminus cytosolic) plasma membrane proteins was found to be non-random. In this sample, Ile was preferentially localized to the amino-terminal region of the hydrophobic transmembrane segments, followed by Val, while Leu predominated in the carboxyl-terminal half of the segment. Although Gly residues were preferentially located in the transmembrane segment, this residue was excluded from the carboxyl-terminal and adjacent boundary regions. Aromatic residues (Tyr, Trp and Phe) occurred preferentially at the cytoplasmic boundary, with Trp also favored at the extracellular boundary. The extracellular flanking sequence amino terminal to the transmembrane segment was enriched in residues predicted to initiate helix formation (Pro, Asn and Ser), while Arg and Lys were enriched in the cytoplasmic flank where they may function as topological determinants. The positional preferences of these particular amino acids within the transmembrane segment and flanking regions suggests that, in addition to lipid-protein interactions, these residues may participate in specific protein-protein interactions. A consensus sequence motif for type I membrane proteins is proposed and its role in the biosynthesis, folding, assembly and function of these segments is discussed. PMID- 8433363 TI - Negative supercoiling and nucleosome cores. I. The effect of negative supercoiling on the efficiency of nucleosome core formation in vitro. AB - The efficiency of nucleosome core formation in vitro as a function of DNA topology was investigated. We show that the reconstitution of nucleosome cores by urea/salt dialysis on both negatively supercoiled and linearized plasmid proceed co-operatively, and that negatively supercoiled molecules are reconstituted significantly more efficiently compared with linearized molecules. The free energy of supercoiling, related to the square of the linking deficit, is further shown to be sufficient to account for this difference, which is particularly pronounced at low molar reconstitution ratios of octamer: DNA. At these low molar ratios the average number of cores formed per negatively supercoiled molecule is equal to the input ratio of octamer: DNA, in contrast to linearized molecules, where few if any cores are reconstituted under identical experimental conditions. The possible contribution of supercoil-stabilized non-B-DNA structural transitions to differences in core-DNA interactions on supercoiled and linearized DNA was also investigated. We show that the change in the nuclease susceptibility of a d(A-G).d(C-T) run in the free and reconstituted supercoiled plasmid is consistent with the reversion of the poly(purine).poly(pyrimidine) stretch from an H-DNA form to a B-DNA form following reconstitution of the negatively supercoiled plasmid into nucleosome cores. The biological significance of the supercoil-dependent efficiency of core formation is discussed, and the results related to other work. PMID- 8433364 TI - Negative supercoiling and nucleosome cores. II. The effect of negative supercoiling on the positioning of nucleosome cores in vitro. AB - The influence of unrestrained negative superhelical stress on nucleosome core positioning was investigated in vitro for a core located on a section of the early H1-H4 histone gene spacer of Psammechinus miliaris. We show that the position of this core on a reconstituted molecule occupied by 11 nucleosome cores is identical on a linear DNA molecule and a circular DNA molecule in the absence of unrestrained negative superhelical stress. This position is also identical to that previously found on a 337 base-pair fragment of corresponding sequence. We conclude that the core position is determined primarily by the DNA sequence, and is not influenced by core-core interactions or spatial constraints imposed by an altered geometry of the DNA molecule. This finding is supported by the identical positions assumed by the nucleosome core after altering the angular orientation of the DNA molecule, and presumably that of adjacent cores, on either one or both sides of the test core. It is further demonstrated that the core on the histone spacer region assumes identical positions on circular DNA molecules in both the presence and absence of excess negative superhelical stress equivalent to sigma = -0.03. This result indicates that conservative levels of negative supercoiling do not induce a shift in the positions of nucleosome cores. The biological implications of the experimental results are discussed and related to the findings of other workers. PMID- 8433365 TI - Role of DNA-protein interactions in bacteriophage phi X174 DNA injection. AB - Like most bacteriophages, phi X174 transfers its DNA through the cell wall, leaving an empty capsid on the cell surface. The process begins with ejection of the genome at its host-receptor site. The rate of this event can be measured, so detailed structure/function analysis of the mechanism is possible now that an atomic structure of the phi X174 protein shell has been obtained. Amino acid substitutions at two arginine residues near the DNA-binding pocket of F capsid protein decrease the eclipse rate, while deletion of 27 bases from the J-F non coding region increases the rate. An alanine to serine change in the N-terminal region of the phi X174 H "spike" protein has suppressor activity in that this mutation also increases the eclipse rate when the complete genome is present within both mutant and wild-type F capsids. These results suggest that a portion of H protein is inside the capsid, and disruption of DNA-protein interactions is involved in the ejection mechanism. PMID- 8433366 TI - Requirements of a group I intron for reactions at the 3' splice site. AB - Structural elements of the Tetrahymena group I intron have been implicated in directing the exon-ligation transesterification reaction (the second step of self splicing) to the correct 3' splice site. The 3' splice site also serves as the reaction site in a distinct transesterification reaction known as G-exchange and in a specific hydrolysis reaction. The dependence of the reactions on the internal guide sequence (IGS), an exon-binding element, was examined. Hydrolysis did not require the IGS, while G-exchange did, suggesting that one of the guanosine-binding sites employed during G-exchange requires the IGS. For the exon ligation reaction, the specification of the 3' splice site is thought to be influenced by the 3' exon-IGS pairing P10 and three structural elements in the intron: the universally conserved guanosine residue preceding the 3' splice site, the long-range pairing P9.0, and the triple stem-loop region composed of P9, P9.1 and P9.2. A systematic mutational study of the three structural elements was performed in order to clarify the mechanism of the specification of the 3' splice site for the reactions. For both transesterification reactions, the elements are important, with some superfluity in function. The specific hydrolysis reaction, however, shows even more dependence on the individual elements, especially the conserved guanosine. The results are discussed in terms of models for the mechanism of self-splicing. PMID- 8433367 TI - Solution structure of a variant of human pancreatic secretory trypsin inhibitor determined by nuclear magnetic resonance spectroscopy. AB - The structure of a variant of human pancreatic secretory trypsin inhibitor (PSTI) has been determined by 1H nuclear magnetic resonance (n.m.r.) spectroscopy and a combination of distance geometry and molecular dynamics simulations. After complete assignment of the 1H signals, the nuclear Overhauser data imply the existence of a rather well-determined tertiary structure stabilized by a central alpha-helix and a short three-stranded beta-sheet. The tertiary structure of the amino terminus and of the loop 11-17 could not be defined by n.m.r. data, suggesting a high flexibility in these areas. As the crystal structures of two complexes of human PSTI variants and that of an uncomplexed variant are also known a comparison of the PSTI tertiary structure in solution and in the crystal is now possible. PMID- 8433368 TI - Refined solution structures of the Escherichia coli trp holo- and aporepressor. AB - The solution structures of the trp-repressor from Escherichia coli in both the liganded (holo-) and unliganded (apo-) form, have been refined by restrained molecular dynamics with simulated annealing using the program XPLOR and additional experimental constraints. The ensemble of refined holorepressor structures have a root-mean-square deviation (r.m.s.d.) of 0.8 A relative to the average structure for the backbone of the dimer core (helices A, B, C, A', B', C') and 2.5 A for the helix-turn-helix DNA-binding domain (helices D and E). The corresponding values for the aporepressor are 0.9 A for the backbone of the ABC dimer core and 3.2 A for the DE helix-turn-helix. The r.m.s.d. of the average structures from the corresponding crystal structures are 2.3 A for the holorepressor ABC core and 4.2 A for its DE region; 2.3 A for the aporepressor core and 5.5 A for its DE region. The relative disorder of the DNA-binding domain is reflected in a number of experimental parameters including substantially more rapid backbone proton exchange rates, exchange-limited relaxation times and crystallographic B-factors. The stabilizing effect of the L-Trp ligand is evident in these measurements, as it is in the higher precision of the holorepressor structure. PMID- 8433369 TI - Similar hydrophobic replacements of Leu99 and Phe153 within the core of T4 lysozyme have different structural and thermodynamic consequences. AB - Two bulky amino acids within the core of phage T4 lysozyme have each been replaced in turn with a series of hydrophobic amino acids. In one set of experiments, Leu99 was replaced with Phe, Met, Ile, Val and Ala. In the second series, Phe153 was replaced with Leu, Met, Ile, Val and Ala. The double mutant in which both Leu99 and Phe153 were replaced with alanine was also constructed. The change in stability of the protein associated with each substitution and the crystal structure of each variant have been determined. In the case of replacements at position 99 the protein behaves in a relatively rigid manner, and changes very little in response to substitutions. In contrast, the protein is more flexible and adjusts much more in response to substitutions of Phe153. In both cases there is a roughly linear dependence between the stability of the mutant protein relative to wild-type (delta delta G) and the difference in the hydrophobic strength of the amino acids involved in the substitution based on solvent transfer measurements (delta delta Gtr). The change in delta delta G is, however, much greater than delta delta Gtr. For the Phe153 replacements the discrepancy is about 1.9-fold, while for the Leu99 series it is about 2.6-fold. Mutants such as Leu99-->Ala, for which the protein remains essentially rigid, tend to create larger cavities and so incur a larger energy of destabilization. Mutants such as Phe153-->Ala, for which the protein structure tends to relax, result in smaller cavities and so are less destabilized. Mutants L99I and L99V are less stable than expected from considerations of transfer free energy and cavity formation due to introduced strain caused by the replacement of Leu99 with a residue of different shape. Mutant F153L is more stable than the reference wild type, even though the transfer free energy of Leu is less than that of Phe. The increase in stability is apparently due to torsional strain in the side-chain of Phe153 that is present in wild-type lysozyme, but is relieved in the mutant structure. PMID- 8433370 TI - Functional interactions among the His40, Glu58 and His92 catalysts of ribonuclease T1 as studied by double and triple mutants. AB - We report on the functional interplay between the His40, Glu58 and His92 catalysts of ribonuclease T1. The kinetic properties of the single His40Ala, Glu58Ala and His92Gln mutants have been compared with those of the corresponding double and triple mutants. When His40, Glu58 and His92 are mutated separately or together, we observe large effects on turnover but only minor effects on substrate binding. The free energy barriers to kcat introduced by the single His40Ala, Glu58Ala and His92Gln mutations are non-additive in the corresponding His40Ala + Glu58Ala, Glu58Ala + His92Gln and His40Ala + His92Gln double mutants; a significant dependence of the pairwise interactions on the third residue has been observed. Using a pair of related triple mutant boxes, we were able to divide the apparent coupling energies as calculated from the kinetic parameters of the various mutants either quantitatively or qualitatively into terms that measure intrinsic interaction energies between His40, Glu58 and His92 in wild type enzyme and terms that account for a change in reaction mechanism that is associated with the Glu58Ala single mutation. In most cases, non-additivity may be explained by changes in enzyme mechanism. Apart from this change in mechanism, functional interactions have to be considered between His40 and Glu58, Glu58 and His92 as well as between His40 and His92 to explain non-additivity in all double mutant cycles. It is concluded that the collaborative effects of His40, Glu58 and His92 decrease the energetic barrier to kcat by 6.8 kcal/mol. The overall effect caused by the triple mutation is smaller than that expected from the product of the fractional kcat values resulting from the individual mutations (11.0 kcal/mol), illustrating the limitations of using single mutants to probe the energetics of a catalytic group whose function is dependent upon interactions with others. PMID- 8433371 TI - Crystallization and preliminary X-ray analysis of an NAD(+)-dependent alcohol dehydrogenase from the extreme thermophilic archaebacterium Sulfolobus solfataricus. AB - An NAD(+)-dependent alcohol dehydrogenase from the extreme thermophilic archaebacterium Sulfolobus solfataricus has been crystallized in the holo-enzyme and apo-enzyme forms. Crystals of the holo-enzyme grow from 2-methyl-2,4 pentanediol at pH 8.4 with the addition of NADH and at pH 7.0 with the addition of NADH and dimethyl sulphoxide. Crystals of the apo-enzyme grow at pH 6.3 from a mixture of polyethylene glycol 4000 and propan-2-ol. The holo-enzyme crystallizes in C2 with a dimer in the asymmetric unit, however the crystals are twinned and unsuitable for data collection. The apo-enzyme crystallizes in I4(1)22 (a = 126.82 A, b = 118.95 A) with a monomer in the asymmetric unit, and the single crystals diffract to 2.8 A. PMID- 8433372 TI - Preliminary investigation of crystals of lipase I from Rhizopus niveus. AB - Lipase I from Rhizopus niveus consists of two polypeptide chains bound non covalently. Lipase I has been crystallized in a form suitable for X-ray diffraction analysis using the hanging drop method of vapour diffusion at 20 degrees C. The crystals grew at pH 6.0 to 7.0 using 14 to 16% polyethylene glycol 8000 as the precipitant. The crystals are tetragonal with space group P4(1) (or P4(3)) and cell dimensions of a = b = 83.7 A, c = 137.9 A. There are two protein molecules in the asymmetric unit. The diffraction pattern extends to at least 2.5 A resolution. PMID- 8433373 TI - Crystallization of F1-ATPase from bovine heart mitochondria. AB - Crystals of the F1-ATPase sector of the ATP synthase complex from bovine heart mitochondria have been grown from solutions containing polyethylene glycol 6000. The crystals diffract to 2.9 A resolution on a laboratory X-ray source. They are orthorhombic and belong to the space group P2(1)2(1)2(1). The unit cell axes are a = 285 A, b = 108 A, c = 140 A. There is one molecule of F1-ATPase in the asymmetric unit. PMID- 8433374 TI - Crystallization and preliminary X-ray analysis of the periplasmic fragment of CyoA-a subunit of the Escherichia coli cytochrome o complex. AB - CyoA, an integral membrane protein, is a subunit of the Escherichia coli cytochrome o quinol oxidase complex. The C-terminal periplasmic domain of CyoA has been expressed in E. coli, purified and crystallized. Crystals were grown using ammonium sulphate as a precipitant. They have space group I222 or I2(1)2(1)2(1) and diffract X-rays to 2.3 A resolution. PMID- 8433375 TI - Characterization of a multigene family encoding an exopolygalacturonase in maize. AB - Genes coding for exopolygalacturonase in plants are abundantly expressed during the development of the male gametophyte (pollen). We have analysed genomic and cDNA clones for several representatives of the small multigene family encoding exopolygalacturonase from Zea mays. Structures for both actively transcribed genes and non-transcribed pseudogenes are reported. Comparisons of the nucleotide sequences for coding and flanking regions of different members of the gene family reveal surprisingly few base substitutions, suggesting that the exopolygalacturonase gene family of maize arose through very recent multiple duplication events. The pseudogenes are shown to possess an 80 bp insertion within the coding region, which may represent a relictual intron that has been lost in the active genes. We estimate that 12 exopolygalacturonase genes exist in maize. None appear to be expressed at a detectable level in tissue other than those associated with pollen development. PMID- 8433376 TI - The evolutionary relationship of avian and mammalian myosin heavy-chain genes. AB - Sequence comparisons of avian and mammalian skeletal and cardiac myosin heavy chain isoforms are used to examine the evolutionary relationships of sarcomeric myosin multigene families. Mammalian fast-myosin heavy-chain isoforms from different species, with comparable developmental expression, are more similar to each other than they are to other fast isoforms within the same genome. In contrast, the developmentally regulated chicken fast isoforms are more similar to each other than they are to myosin heavy-chain isoforms in other species. Extensive regions of nucleotide identity among the chicken fast myosin heavy chains and in the mouse and rat alpha- and beta-cardiac myosin heavy-chain sequences suggest that gene-conversion-like mechanisms have played a major role in the concerted evolution of these gene families. We also conclude that the chicken fast myosin heavy-chain multigene family has undergone recent expansion subsequent to the divergence of birds and mammals and that both the developmental regulation and the specialization of myosin isoforms have likely developed independently in birds and mammals. PMID- 8433377 TI - Region-specific rates of molecular evolution: a fourfold reduction in the rate of accumulation of "silent" mutations in transcribed versus nontranscribed regions of homologous DNA fragments derived from two closely related mouse species. AB - We have sequenced homologous DNA fragments of 2.7 and 2.8 kbp derived from the closely related mouse species Mus musculus domesticus (M. domesticus) and Mus musculus musculus (M. musculus), respectively. These two species diverged approximately 1 million years ago. Each DNA fragment contains 1.35 kbp of the 3' end of the constitutively expressed 2.2-kbp aprt (adenine phosphoribosyltransferase) gene and a similarly sized nontranscribed region downstream of the aprt gene. The aprt gene region contains protein coding sequences (0.35 kbp), intronic sequences (0.75 kbp), and a 3' nontranslated sequence (0.25 kbp). Both the M. domesticus and M. musculus downstream regions share three partial copies of the B1 repetitive element with the M. musculus downstream region containing an additional complete copy of this element. A comparison of the 2.7- and 2.8-kbp DNA fragments revealed a total of 63 molecular alterations (i.e., mutations) that were approximately fourfold more abundant in the nontranscribed downstream region than in the transcribed aprt gene. Of the 11 mutations observed in the transcribed region, 7 were found in introns, 3 in the 3' untranslated sequence, and 1 was a synonymous change in an exon. A comparison of the human and M. domesticus aprt genes has previously revealed no homology in either the intronic or 3' nontranslated regions with the exception of a 26-bp sequence in intron 3 and sequences at the exon/intron boundaries necessary for correct mRNA splicing (Broderick et al., Proc. Natl. Acad. Sci. USA, 84:3349, 1987). Therefore, there does not appear to be selective pressure for sequences within these regions. We conclude that there is a lower rate of accumulation of "silent" mutations in the transcribed mouse aprt gene than in a contiguous nontranscribed downstream region. A possible molecular mechanism involving preferential DNA repair for the transcribed region is discussed. PMID- 8433378 TI - Evolution of protein complexity: the blue copper-containing oxidases and related proteins. AB - The blue copper proteins and their relatives have been compared by sequence alignments, by comparison of three-dimensional structures, and by construction of phylogenetic trees. The group contains proteins varying in size from 100 residues to over 2,300 residues in a single chain, containing from zero to nine copper atoms, and with a broad variation in function ranging from electron carrier proteins and oxidases to the blood coagulation factors V and VIII. Difference matrices show the sequence difference to be over 90% for many pairs in the group, yet alignment scores and other evidence suggest that they all evolved from a common ancestor. We have attempted to delineate how this evolution took place and in particular to define the mechanisms by which these proteins acquired an ever increasing complexity in structure and function. We find evidence for six such mechanisms in this group of proteins: domain enlargement, in which a single domain increases in size from about 100 residues up to 210; domain duplication, which allows for a size increase from about 170 to about 1,000 residues; segment elongation, in which a small segment undergoes multiple successive duplications that can increase the chain size 50-fold; domain recruitment, in which a domain coded elsewhere in the genome is added on to the peptide chain; subunit formation, to form multisubunit proteins; and glycosylation, which in some cases doubles the size of the protein molecule. Size increase allows for the evolution of new catalytic properties, in particular the oxidase function, and for the formation of coagulation factors with multiple interaction sites and regulatory properties. The blood coagulation system is examined as an example in which a system of interacting proteins evolved by successive duplications of larger parts of the genome. The evolution of size, functionality, and diversity is compared with the general question of increase in size and complexity in biology. PMID- 8433379 TI - The evolution of proteins from random amino acid sequences. I. Evidence from the lengthwise distribution of amino acids in modern protein sequences. AB - We examine in this paper one of the expected consequences of the hypothesis that modern proteins evolved from random heteropeptide sequences. Specifically, we investigate the lengthwise distributions of amino acids in a set of 1,789 protein sequences with little sequence identify using the run test statistic (ro) of Mood (1940, Ann. Math. Stat. 11, 367-392). The probability density of ro for a collection of random sequences has mean = 0 and variance = 1 [the N(0,1) distribution] and can be used to measure the tendency of amino acids of a given type to cluster together in a sequence relative to that of a random sequence. We implement the run test using binary representations of protein sequences in which the amino acids of interest are assigned a value of 1 and all others a value of 0. We consider individual amino acids and sets of various combinations of them based upon hydrophobicity (4 sets), charge (3 sets), volume (4 sets), and secondary structure propensity (3 sets). We find that any sequence chosen randomly has a 90% or greater chance of having a lengthwise distribution of amino acids that is indistinguishable from the random expectation regardless of amino acid type. We regard this as strong support for the random-origin hypothesis. However, we do observe significant deviations from the random expectation as might be expected after billions years of evolution. Two important global trends are found: (1) Amino acids with a strong alpha-helix propensity show a strong tendency to cluster whereas those with beta-sheet or reverse-turn propensity do not. (2) Clustered rather than evenly distributed patterns tend to be preferred by the individual amino acids and this is particularly so for methionine. Finally, we consider the problem of reconciling the random nature of protein sequences with structurally meaningful periodic "patterns" that can be detected by sliding-window, autocorrelation, and Fourier analyses. Two examples, rhodopsin and bacteriorhodopsin, show that such patterns are a natural feature of random sequences. PMID- 8433381 TI - Unbiased estimation of the rates of synonymous and nonsynonymous substitution. AB - The current convention in estimating the number of substitutions per synonymous site (KS) and per nonsynonymous site (KA) between two protein-coding genes is to count each twofold degenerate site as one-third synonymous and two-thirds nonsynonymous because one of the three possible changes at such a site is synonymous and the other two are nonsynonymous. This counting rule can considerably overestimate the KS value because transitional mutations tend to occur more often than transversional mutations and because most transitional mutations at twofold degenerate sites are synonymous. A new method that gives unbiased estimates is proposed. An application of the new and the old method to 14 pairs of mouse and rat genes shows that the new method gives a KS value very close to the number of substitutions per four-fold degenerate site whereas the old method gives a value 30% higher. Both methods give a KA value close to the number of substitutions per nondegenerate site. PMID- 8433380 TI - The evolution of long interspersed repeated DNA (L1, LINE 1) as revealed by the analysis of an ancient rodent L1 DNA family. AB - All modern mammals contain a distinctive, highly repeated (> or = 50,000 members) family of long interspersed repeated DNA called the L1 (LINE 1) family. While the modern L1 families were derived from a common ancestor that predated the mammalian radiation approximately 80 million years ago, most of the members of these families were generated within the last 5 million years. However, recently we demonstrated that modern murine (Old World rats and mice) genomes share an older long interspersed repeated DNA family that we called Lx. Here we report our analysis of the DNA sequence of Lx family members and the relationship of this family to the modern L1 families in mouse and rat. The extent of DNA sequence divergence between Lx members indicates that the Lx amplification occurred about 12 million years ago, around the time of the murine radiation. Parsimony analysis revealed that Lx elements were ancestral to both the modern rat and mouse L1 families. However, we found that few if any of the evolutionary intermediates between the Lx and the modern L1 families were extensively amplified. Because the modern L1 families have evolved under selective pressure, the evolutionary intermediates must have been capable of replication. Therefore, replication competent L1 elements can reside in genomes without undergoing extensive amplification. We discuss the bearing of our findings on the evolution of L1 DNA elements and the mammalian genome. PMID- 8433382 TI - Accumulation of adenine and thymine in a groE-homologous operon of an intracellular symbiont. AB - As a result of the nucleotide sequence analysis of an aphid endosymbiont's operon homologous to the Escherichia coli groE, we noted that directional base substitutions tending toward an increase of A + T content represent an obvious evolutionary trend in this prokaryotic operon, housed for a long period by an eukaryotic cell. This result, when taken together with previous reports, raised the possibility that genomic DNA of prokaryotes residing in an eukaryotic cell is subject to A/T-biased directional mutation pressure and/or both negative and positive selection operating under conditions specific to the intracellular environments. PMID- 8433383 TI - Molecular evolution of the intergenic spacer in the nuclear ribosomal RNA genes of cucurbitaceae. AB - The intergenic spacer (IGS) of a 10-kbp repeat (clone pRZ7D) of the nuclear 18S, 5.8S, and 25S ribosomal RNA genes of Cucurbita pepo (zucchini) was sequenced and compared to the IGS sequences of two other Cucurbitaceae, Curcurbita maxima (squash), and Cucumis sativus (cucumber). The nucleotide sequence and the structural organization of the IGS of C. pepo and C. maxima are rather similar (between 75 and 100% sequence similarity depending on the region compared). The IGS are mainly composed of three different repeated elements interspersed into unique sequences: GC-rich clusters, a 422-bp AT-rich element including the transcription initiation site (TIS) for RNA polymerase I, and 260-bp repeats in the 5' external transcribed spacer (D repeats). The TIS is duplicated in the 10 kbp repeat class of C. pepo, as it is also described for the 11.5-kbp rDNA repeat of C. maxima. The IGS of Cucumis sativus is also composed of different repeated elements; however, obvious sequence identity to the Cucurbita species only occurs around the TIS and the preceding AT-rich region. GC-rich clusters with different primary sequences are present in the IGS of all three plants. Remarkably, the repeated elements in the 5'ETS accumulate TpG and TpNpG motifs, whereas CpG and CpNpG motifs less frequently occur. This accumulation might be caused by the transition of methylated cytosines (in mCpG or mCpNpG motifs) into thymidine via deamination in a previously GC-rich ancestor. The following singular region exhibits 50% G + C in C. pepo, 53% G+C in C. maxima, and 63% G + C in C. sativus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433384 TI - Divergence pattern and selective mode in protein evolution: the example of vertebrate myoglobins and hemoglobin chains. AB - The evolutionary relation of vertebrate myoglobin and the hemoglobin chains including the agnathan hemoglobin chain is investigated on the basis of a new view of amino acid changes that is developed by canonical discriminant analysis of amino acid residues at individual sites. In contrast to the clear discrimination of amino acid residues between myoglobin, hemoglobin alpha chain, and hemoglobin beta chain in warm-blood vertebrates, the three types of globins in the lower class of vertebrates show so much variation that they are not well discriminated. This is seen particularly at the sites that are ascertained in mammals to carry the amino acid residues participating in stabilizing the monomeric structure in myoglobin and the residues forming the subunit contacts in hemoglobin. At these sites, agnathan hemoglobin chains are evaluated to be intermediate between the myoglobin and hemoglobin chains of gnathostomes. The variation in the phylogenetically lower class of globins is also seen in the internal region; there the amino acid residues of myoglobin and hemoglobin chains in the phylogenetically higher class exhibit an example of parallel evolution at the molecular level. New quantities, the distance of sequence property between discriminated groups and the variation within each group, are derived from the values of discriminant functions along the peptide chain, and this set of quantities simply describes an overall feature of globins such that the distinction between the three types of globins has been clearer as the vertebrates have evolved to become jawed, landed, and warm-blooded. This result strongly suggests that the functional constraint on the amino acid sequence of a protein is changed by living conditions and that severe conditions constitute a driving force that creates a distinctive protein from a less-constrained protein. PMID- 8433385 TI - TRK-a expression in neuroblastomas: a new prognostic marker with biological and clinical significance. PMID- 8433386 TI - ACS keeps mammography guidelines for women under 50. PMID- 8433387 TI - Europeans say screen only women age 50 and older. PMID- 8433388 TI - Vasectomy linked to increased risk for prostate cancer. PMID- 8433389 TI - Oral contraceptives and breast cancer. PMID- 8433390 TI - The European Organization for Research and Treatment of Cancer QLQ-C30: a quality of-life instrument for use in international clinical trials in oncology. AB - BACKGROUND: In 1986, the European Organization for Research and Treatment of Cancer (EORTC) initiated a research program to develop an integrated, modular approach for evaluating the quality of life of patients participating in international clinical trials. PURPOSE: We report here the results of an international field study of the practicality, reliability, and validity of the EORTC QLQ-C30, the current core questionnaire. The QLQ-C30 incorporates nine multi-item scales: five functional scales (physical, role, cognitive, emotional, and social); three symptom scales (fatigue, pain, and nausea and vomiting); and a global health and quality-of-life scale. Several single-item symptom measures are also included. METHODS: The questionnaire was administered before treatment and once during treatment to 305 patients with nonresectable lung cancer from centers in 13 countries. Clinical variables assessed included disease stage, weight loss, performance status, and treatment toxicity. RESULTS: The average time required to complete the questionnaire was approximately 11 minutes, and most patients required no assistance. The data supported the hypothesized scale structure of the questionnaire with the exception of role functioning (work and household activities), which was also the only multi-item scale that failed to meet the minimal standards for reliability (Cronbach's alpha coefficient > or = .70) either before or during treatment. Validity was shown by three findings. First, while all interscale correlations were statistically significant, the correlation was moderate, indicating that the scales were assessing distinct components of the quality-of-life construct. Second, most of the functional and symptom measures discriminated clearly between patients differing in clinical status as defined by the Eastern Cooperative Oncology Group performance status scale, weight loss, and treatment toxicity. Third, there were statistically significant changes, in the expected direction, in physical and role functioning, global quality of life, fatigue, and nausea and vomiting, for patients whose performance status had improved or worsened during treatment. The reliability and validity of the questionnaire were highly consistent across the three language-cultural groups studied: patients from English-speaking countries, Northern Europe, and Southern Europe. CONCLUSIONS: These results support the EORTC QLQ-C30 as a reliable and valid measure of the quality of life of cancer patients in multicultural clinical research settings. Work is ongoing to examine the performance of the questionnaire among more heterogenous patient samples and in phase II and phase III clinical trials. PMID- 8433391 TI - Lack of high-affinity nerve growth factor receptors in aggressive neuroblastomas. AB - BACKGROUND: Neuroblastoma is a malignancy of the sympathetic nervous system. Nerve growth factor, which has a major role in development of the sympathetic nervous system, has high-affinity (gp140TRK-A) and low-affinity (gp75NGFR) cell surface receptors. We recently reported preliminary study results showing a lack of gp140TRK-A receptors and rapid disease progression in neuroblastomas, particularly those with amplification of the N-myc (also known as MYCN) proto oncogene. PURPOSE: This retrospective study was designed to determine if expression of nerve growth factor receptor messenger RNA (mRNA) was associated with biologic and clinical parameters and with survival in neuroblastoma. METHODS: We obtained 80 untreated primary neuroblastomas that had been snap frozen and stored after surgical excision. To determine expression of gp140TRK-A and gp75NGFR, we performed Northern blot analyses on total RNA from the specimens. Samples from the same specimens were examined for N-myc proto-oncogene amplification, RNA expression, and histologic differentiation, and clinical stage at diagnosis and survival were determined. RESULTS: Of the 80 neuroblastomas, 65 (81%) expressed gp140TRK-A RNA. However, three (27%) of the 11 tumors with genomic amplification and high expression of N-myc RNA and 62 (90%) of the 69 without genomic amplification or detectable N-myc RNA expressed gp140TRK-A mRNA. The inverse relationship between gp140TRK-A mRNA and N-myc expression had high statistical significance (P < .0001). Of the 67 tumors assessable for histologic differentiation, the 13 lacking gp140TRK-A mRNA were histologically undifferentiated, whereas 19 (35%) of the 54 expressing it were differentiated (P = .041). Only 10 (53%) of the 19 metastatic (stage IV) tumors expressed gp140TRK A mRNA, compared with 90% for other stages (P = .0003). Survival 2 years after diagnosis was 92%, 78%, and 14% for patients whose tumors expressed high, intermediate, and no gp140TRK-A mRNA, respectively (P < .0001). Univariate and multivariate analyses demonstrated that N-myc and gp140TRK-A expression of mRNA and clinical staging were independent predictors of survival. Expression of gp75NGFR mRNA did not correlate with gp140TRK-A mRNA expression, histologic differentiation, stage, or survival. CONCLUSIONS: The expression of gp140TRK-A mRNA correlates with distinct biologic and clinical subsets of neuroblastoma, which suggests a role for the high-affinity nerve growth factor receptors in determining the phenotype of neuroblastoma. The absence of gp140TRK-A mRNA expression, whether or not the N-myc proto-oncogene is amplified, is associated with tumor progression. PMID- 8433392 TI - Xenografts of primary human prostatic carcinoma. AB - BACKGROUND: Prostatic carcinoma is both the most common invasive cancer and the second most common cause of cancer deaths in men in the United States. Before 1991, attempts to propagate prostatic carcinoma from primary tumors for periods longer than 3 months were unsuccessful in vivo and in vitro with rare exceptions. In 1991, we reported establishment of slowly growing tumors for six of 10 human primary prostatic carcinomas approximately 2-6 months after transplantation. However, none of the tumors were larger than 5 mm or serially transplantable. PURPOSE: Our purpose in this study was to determine whether human primary prostatic carcinoma could be grown as serially transplantable xenografts. METHODS: Cells from primary prostatic carcinomas obtained from transurethral prostatic resections or total prostatectomies in 20 patients were injected subcutaneously into male nude mice on the day of surgery. Sustained-release testosterone pellets were placed subcutaneously in the mice 2-24 days before transplantation of tumors and at intervals of 10-12 weeks. Serial transplantations in subsequent generations of mice were carried out by similar methods. Chromosome analysis was performed on six tumors. RESULTS: Six of 20 primary prostatic carcinomas have grown sufficiently to permit serial transplantation into second mice; four have been documented histopathologically in the second mouse and serially transplanted into three or more successive mice. When a single primary tumor was injected into several mice by the same procedure, tumors failed to grow in some recipients but became serially transplantable in others. Growth of these tumors is slow and irregular, with frequent regressions. Short-term cultures of 10 tumors, eight of which were injected into mice in parallel, were initiated on the day of surgery; CWR31, which was successfully transplanted serially, exhibited only aberrant metaphases and showed clonal, chromosomal changes in culture. Including CWR31, three of the six tumors for which chromosomal analysis was successful contained clonal aberrations. Preliminary studies of SCID (severe combined immunodeficient) mice suggest that they are not superior to nude mice for establishment of serially transplantable prostatic carcinoma xenografts. CONCLUSIONS: A proportion of human primary prostatic carcinomas can be grown as xenografts. Four new serially transplantable xenografts (CWR21, CWR31, CWR91, and CWR22) are currently propagated in our laboratory, a resource that was not previously available. IMPLICATIONS: Our experience suggests that the most important factor in serial transplantation is the collaboration of urologists and pathologists in expediting placement of the tumor in cold saline, examination of the frozen section, and transplantation. PMID- 8433394 TI - Protein kinase C: a novel target for inhibiting gastric cancer cell invasion. AB - BACKGROUND: Gastric adenocarcinoma is a common neoplasm worldwide. Patients with completely resected disease often have locoregional recurrence, and adjuvant chemotherapy has failed to reduce the common occurrence of metastases. Protein kinase C (PKC) is thought to be important in tumor cell invasion, but its relationship to gastric cancer cell invasion, and thus metastases, remains unexplored. We recently identified and established invasive and noninvasive human gastric adenocarcinoma cell lines, which can now be used to test agents for inhibition of tumor cell invasion by inhibition of PKC activity. PURPOSE: The objectives were (a) to test threo-dihydrosphingosine (SPC100221), a specific inhibitor of PKC at its regulatory site, and staurosporine, a potent but nonspecific inhibitor of PKC at its catalytic site, for their effects on gastric cancer cell invasion in vitro and (b) to determine whether the expression of PKC isoforms can distinguish invasive from noninvasive gastric cancer cells. METHODS: Gastric cancer cell invasion through Matrigel-coated Nuclepore filters in the Boyden chamber assay was analyzed in the presence of graded concentrations of SPC100221 and staurosporine. The invasive SK-GT-1 and SK-GT-5 cell lines and the noninvasive SK-GT-2 and SK-GT-4 cell lines were used. PKC isoform expression was determined by reverse transcription of messenger RNAs to complementary DNA and subsequent amplification by the polymerase chain reaction. RESULTS: The effects of staurosporine and SPC100221 on tumor cell invasion were tested at drug concentrations that did not inhibit cell proliferation, as evidenced by [3H]thymidine uptake. Staurosporine and SPC100221 at subtoxic doses inhibited human gastric cancer cell invasion by 50% at 5 x 10(-9) M and 2 x 10(-7) M, respectively. The expression of PKC beta was observed in the invasive but not the noninvasive gastric cancer cells. Both types of cells, however, expressed the PKC alpha and PKC gamma isoforms. CONCLUSIONS: Gastric cancer cell invasion can be inhibited by PKC inhibitors, and expression of PKC beta may be a marker of invasiveness in gastric cancer. IMPLICATIONS: PKC appears to represent a new target for inhibition of gastric cancer cell invasion, and SPC100221, in view of its PKC specificity, may provide a model for future drug development in this area. Moreover, PKC beta may have a fundamental role in the development of invasive potential in gastric cancer. PMID- 8433393 TI - Prognostic significance of the 67-kilodalton laminin receptor expression in human breast carcinomas. AB - BACKGROUND: The 67-kd laminin receptor is a cell-surface protein that binds laminin with high affinity. In vitro studies suggest that this protein is involved in the progression of human tumors to invasive cancers (metastasis), but there have been few in vivo studies. Identification of such proteins would allow development of therapies aimed at interfering with their mechanisms of action. PURPOSE: This large retrospective study was designed to investigate the association of expression of this laminin receptor molecule with established prognostic factors and overall survival in breast carcinoma patients. METHODS: We immunohistochemically stained archival paraffin-embedded sections of 1160 primary breast carcinomas, using an immunoperoxidase technique and the MLuC5 monoclonal antibody, which is specific for the 67-kd laminin receptor. Specimens were obtained from consecutive surgeries performed from January 1968 through December 1971. Patients with negative lymph nodes or involved regional nodes had been treated with surgery alone; those with positive axillary nodes had received surgery and radiotherapy. No chemotherapy had been administered until disease recurrence. The statistical analysis was carried out using the logrank method for the survival curves and the actuarial life table to calculate survival rates according to the different prognostic variables. RESULTS: We found statistically significant associations between laminin receptor expression and young age (P < .001), premenopausal status (P = .001), positive axillary lymph nodes (P = .01), peritumoral lymphatic invasion (P = .02), and the diameter of the tumor (P = .05). Moreover, the association of expression of the receptor protein with poor prognosis, as indicated by survival curves, was statistically significant (P < .01). For patients with receptor-negative tumors, the survival rate was 50% at 20 years; for those with receptor-positive tumors, the survival rate was 50% at 13 years. Multivariate analysis showed the laminin receptor to be an independent prognostic factor (P = .005), indicating its predictive value in relation to overall survival. CONCLUSIONS: Our data suggest that the 67-kd laminin receptor is associated with the metastatic process. IMPLICATIONS: These preliminary findings also suggest that hormones may have a regulatory role in the in vivo expression of the 67-kd laminin receptor, which supports the hypothesis that hormone therapy might inhibit expression of the receptor. Studies of expression of this receptor in tumors of patients with extremely different sex hormone levels (e.g., men and pregnant women) are in progress. PMID- 8433395 TI - Phase II study of interferon-gamma and interleukin-2: tachyphylaxis of toxicity to the liver during increasing immune enhancement. PMID- 8433396 TI - Differential effects of triphenylphosphite and diisopropyl phosphorofluoridate on catecholamine secretion from bovine adrenomedullary chromaffin cells. AB - Types I and II organophosphorus compound-induced delayed neurotoxicity (OPIDN) is characterized by axonal degeneration. Type II compounds, however, uniquely cause cell body damage. Primary cultures of bovine adrenomedullary chromaffin cells were used to investigate and assess biochemically the cell body effects of the Type II compound triphenyl phosphite (TPP). Exocytotic secretion of neurotransmitter was measured to determine whether the cytotoxic action of TPP compromised synaptic events. TPP inhibited catecholamine secretion in both a time and dose-dependent manner. By 4 h, TPP had inhibited nicotine-induced secretion by about 85%. TPP inhibited catecholamine secretion by about 35% as early as 15 min. The IC50 for TPP was about 45 microM. TPP inhibited secretion regardless of the secretagogue used, although nicotine-induced secretion was inhibited to the greatest extent. The Type I OPIDN diisopropyl phosphorofluoridate (DFP) and the nondelayed-type neurotoxic organophosphorus compound O,O-diethyl-O-4-nitrophenyl phosphate (paraoxon) did not inhibit catecholamine secretion from these cells. In contrast, when high potassium was used to induce secretion, significant stimulation was observed in the presence of DFP and paraoxon. Since Ca2+ homeostasis plays a key role in both exocytosis and neuronal necrosis, its uptake into the cells was measured radiometrically in the presence of TPP or DFP. Incubation with 100 microM TPP for 4 h resulted in the inhibition of 45Ca2+ uptake evoked either by nicotine or K+. No significant inhibition of 45Ca2+ uptake was observed in the presence of DFP. TPP and DFP produced 95% and 88% inhibition, respectively, of the activity of the neurotoxic esterase enzyme (NTE), a putative target for OPIDN. Results suggest that these changes in the secretory mechanisms of the cell may be involved in the TPP-induced pathological alterations in chromaffin cells. PMID- 8433397 TI - Cadmium-109 metabolism in mice. I. Organ retention in mice fed a nutritionally sufficient diet during successive rounds of gestation and lactation. AB - Organ retention of 109Cd was studied in multiparous and virgin female mice provided tracer amounts of 109Cd in drinking water and stable Cd appropriate for the itai-itai experience in an otherwise nutrient replete solid diet. Breeder females maximally experienced 6 consecutive, 42-d rounds of gestation/lactation. On a round-by-round basis, breeder organ 109Cd content and concentration values were compared with those from their time-matched virgin controls. By the end of round 5, the 109Cd contents of some organs appeared to have plateaued in consecutive breeders. Comparing breeder with control values at that point, the following increases were observed: whole body (minus gastrointestinal tract), 4.7 fold; mammary tissue, 14.1-fold; liver, 5.9-fold; and kidney, 3.8-fold. For 109Cd concentrations, analogous increases were mammary tissue, 15.3-fold; liver, 4.0 fold; and kidney, 2.4-fold. Through the six rounds, a temporal shift in fractional 109Cd distribution was noted for breeder tissues where transfer occurred from those of the mammaries, remaining carcass, and liver to the kidneys. In spite of this shift, at the end of round 6 109Cd content in hepatic tissue still exceeded that in renal tissue; however, 109Cd concentration was 3.3 fold greater in the kidneys. For virgin female mice over the same period, a relatively smaller shift was observed from remaining carcass to kidneys. Unlike breeders, 109Cd content was identical in hepatic and renal tissues, while 109Cd concentration was 4.6-fold greater in the kidneys. With respect to renal 109Cd increases, the larger portion of these shifts had occurred by the end of round 2 for virgin mice and by the end of round 6 for breeder mice. Comparison of content and concentration measures for a single, time-matched, virgin male group with those from a virgin female group at the end of round 6 revealed distinguishable differences only for the mammary tissues; by either measure these were about threefold higher in the female one. PMID- 8433398 TI - Cadmium-109 metabolism in mice. II. Organ retention in mice fed a nutritionally deficient diet during successive rounds of gestation and lactation. AB - Organ retention of 109Cd was studied in multiparous and virgin female mice provided trace amounts of 109Cd in drinking water and stable Cd as well as certain nutrient minerals, vitamins, and fat all apportioned in solid diet in amounts appropriate for the itai-itai experience. Breeder females maximally experienced 4 nonconsecutive rounds of gestation/lactation in a total of 5 such 42-d periods. On a round-by-round basis, breeder organ 109Cd content and concentration values were compared with those from their time-matched virgin controls. By the end of round 5, most organ 109Cd content values in breeders were still increasing. Relative to control values at that point, the following increases were observed: whole body (minus gastrointestinal tract), 4.7-fold; mammary tissue, 12.5-fold; liver, 4.7-fold; and kidney, 4.8-fold. Analogous increases in 109Cd concentration values were mammary tissue, 9.8-fold; liver, 2.8 fold; and kidney, 2.9-fold. Through the five rounds, a temporal shift in fractional Cd distribution was noted for breeder tissues where transfer occurred from those of the mammaries and remaining carcass to kidneys. Although by the end of the period 109Cd content in the liver still exceeded that in the kidneys, 109Cd concentration was 4.7-fold greater in renal tissues--an increase not matched by other breeder females consuming nutrient-replete rather than nutrient deficient (itai-itai) diet. For virgin female mice over the same period, a shift of similar magnitude was observed from remaining carcass to kidneys. Not unlike the breeders, hepatic 109Cd content again exceeded that in renal tissues, while 109Cd concentration was 4.5-fold greater in the kidneys. With respect to renal 109Cd increases, the greater portion of these shifts had occurred by the end of round 3 for both breeder and virgin mice. Comparison of both content and concentration measures for a single, time-matched, virgin male group with those from a virgin female one at the end of round 3 showed only those for mammary tissues to be distinguishable, and by either measure were about fourfold higher in the female group. PMID- 8433399 TI - Cadmium-109 metabolism in mice. III. Organ retention in mice ovariectomized after experiencing multiple rounds of gestation and lactation. AB - Organ retention of 109Cd was studied in multiparous female mice 6 wk after ovariectomy or sham-control surgery. Females previously had experienced from three to five rounds of gestation/lactation during a maximum of 5 successive, 42 d reproductive periods. Throughout the experiment, mice were provided with tracer amounts of 109Cd in drinking water as well as stable Cd appropriate for the itai itai experience in solid diets otherwise sufficient or deficient in nutrient quality. For sufficient-diet females, organ 109Cd content and concentration values were somewhat lower in the ovariectomized group compared to the sham control group. For deficient-diet females, the opposite trend occurred. When ovariectomized groups were compared with round 5 breeder groups of the same dietary experience, in almost all instances organ 109Cd content and concentration values were lower in the ovariectomized animals. Exceptions to this trend occurred in hepatic and especially renal tissues, where 109Cd concentrations were higher in the deficient-diet, ovariectomized group. Finally, when the deficient diet, ovariectomized group was compared with its sufficient-diet counterpart, significantly higher 109Cd content values were found for liver, kidneys, and whole body (minus GI tract) in the former group. Conversely, when the same tissue content values were compared between the sham-control groups, differences without exception proved to be nonsignificant. PMID- 8433400 TI - Effects of inorganic and organic mercury on intracellular calcium levels in rat T lymphocytes. AB - The importance of cytosolic free calcium level ([Ca2+]i) in lymphocyte activation prompted us to investigate changes in [Ca2+]i in T cells caused by mercury compounds, which have been shown to have immunomodulatory and immunotoxic properties. Using fura-2 as fluorescent Ca2+ indicator, we found that both methyl mercury (MeHg; 0.02-2 microM) and inorganic mercury (HgCl2; 0.01-1 microM) increased [Ca2+]i in lymphocytes from rat spleen in a concentration-dependent manner. The effect of MeHg was rapid and the increase of Ca2+ level was sustained in time, while HgCl2 caused a slow rise in [Ca2+]i. The effects of mercury compounds did not appear to be associated with alterations of membrane integrity, since there was no significant difference in the extent of MnCl2 quench between control and mercury-treated cells. However, HgCl2 (1 microM) and MeHg (2 microM) appeared to cause membrane damage at longer incubation times (15 min). When cells were incubated in Ca(2+)-free medium (in the presence of 1 mM EDTA) MeHg still increased [Ca2+]i, though to a lesser extent, while HgCl2 had no effect. Heparin, an inhibitor of inositol 1,4,5-trisphosphate-induced Ca2+ mobilization partially blocked this rise of [Ca2+]i, while carbonyl cyanide m-chlorophenylhydraxone (CCCP), an inhibitor of mitochondrial function, had a lesser effect. When added together, heparin and CCCP almost completely block the response to MeHg. These results suggest that MeHg and HgCl2 exert their effects of [Ca2+]i in different ways: MeHg-induced increases in [Ca2+]i are due to influx from outside the cells as well as to mobilization from intracellular stores, possibly the endoplasmic reticulum, and, to a minor extent, the mitochondria; on the other hand, HgCl2 causes only Ca2+ influx from the extracellular medium. PMID- 8433401 TI - Protective effects of selenium on cadmium toxicity in rats: role of altered toxicokinetics and metallothionein. AB - Selenium prevents the toxicity of the carcinogenic metal cadmium through undefined mechanisms. In this study, we determined the effects of selenium on cadmium toxicokinetics and on the ability of cadmium to induce metallothionein, a metal-binding protein that is thought to confer tolerance to cadmium toxicity. To assess the acute protective effects of selenium, male Wistar (WF/NCr) rats were given selenium (as SeO2; 10 mumol/kg, sc) at -24, 0, and +24 h relative to cadmium (as CdCl2; 45 mumol/kg, sc). Over a 14-d period this dose of cadmium killed 6 out of 10 rats, while 100% of the cadmium-treated rats given concurrent selenium treatments survived. The acute increases in testicular weight that were seen with cadmium, indicative of edematous damage, were also prevented by concurrent selenium treatments. Further studies assessed the distribution and excretion of cadmium and its ability to induce metallothionein in rats given 40 mumol Cd/kg, sc, at time 0 and selenium (10 mumol/kg, sc) at -24 and 0 h. Selenium treatments enhanced cadmium accumulation at 24 h in the liver (23%), testes (145%), and epididymis (35%) but reduced renal accumulation by more than half. Urine samples, collected at 0-3, 3-6, and 6-24 h following cadmium administration, indicated a markedly reduced excretion of cadmium in selenium treated rats during all time periods. The synthesis of metallothionein was stimulated to a much lesser extent by cadmium in selenium-treated rat kidney (41% decrease) but was unaffected in liver. The levels of cadmium-binding proteins within the testes were markedly reduced by cadmium treatment, an effect unmodified by selenium treatments. These results suggest selenium prevents acute cadmium toxicity through a mechanism that does not involve induction of metallothionein and in spite of a markedly enhanced retention of cadmium. PMID- 8433402 TI - A review of mycotoxins in indoor air. AB - Mycotoxins are chemical compounds, produced by a variety of fungi, that can cause illness in humans and animals. This paper is a review of literature on mycotoxins with emphasis on mycotoxins in indoor air. Consideration is given to specific mycotoxins identified in indoor air, indoor sources of the mycotoxins, factors affecting mycotoxin production, potential health effects indicated by animal laboratory studies, and case studies of possible human inhalation health effects of these mycotoxins. Historically, mycotoxicoses have been associated with consumption of moldy grain. In recent years, some attention has been given to mycotoxins in dust from agricultural environments, but relatively few studies have examined mycotoxins or mycotoxin-producing molds in indoor environments. The few indoor studies suggest that mycotoxicoses may occur in some indoor environments. More studies are needed to understand the potential for mycotoxin occurrence and significance in indoor environments. PMID- 8433403 TI - Insecticide synergists: role, importance, and perspectives. AB - Synergists have been used commercially for about 50 years and have contributed significantly to improve the efficacy of insecticides, particularly when problems of resistance have arisen. In the current article we review the nature, mode of action, role in resistance management, natural occurrence, and significance in research of insecticide synergists. These natural or synthetic chemicals, which increase the lethality and effectiveness of currently available insecticides, are by themselves considered nontoxic. The mode of action of the majority of synergists is to block the metabolic systems that would otherwise break down insecticide molecules. They interfere with the detoxication of insecticides through their action on polysubstrate monooxygenases (PSMOs) and other enzyme systems. The role of synergists in resistance management is related directly to an enzyme-inhibiting action, restoring the susceptibility of insects to the chemical, which would otherwise require higher levels of the toxicant for their control. For this reason synergists are considered straightforward tools for overcoming metabolic resistance, and can also delay the manifestation of resistance. However, the full potential of these compounds may not have been realized in resistance management. Synergists have an important role to play in the ongoing investigation of insecticide toxicity and mode of action and the nature of resistance mechanism. They also can be used in understanding the effects of other xenobiotics in non-target organisms. The search for and the need of new molecules capable of synergizing existing or new pesticides has reactivated the identification and characterization of secondary plant compounds possessing such activity. Plants do possess and utilize synergists to overcome the damage produced by phytophages. This has to be exploited in pest management programs. Hopefully, it will lead to a new perspective on the nature and significance of synergism. PMID- 8433404 TI - Ciguatera. AB - Ciguatera is a type of marine food poisoning produced by the consumption of ciguatoxic reef fish. The disease is of significant concern in many tropical areas where it has been known for centuries. Although mortality from ciguatera is low, morbidity is high and symptoms may be debilitating and prolonged. Ciguatera produces characteristic gastrointestinal, neurological, and to a lesser extent, cardiovascular symptoms. Though the symptoms are relatively well documented, the disease often goes unreported or misdiagnosed. The toxins responsible for ciguatera are produced by marine dinoflagellates associated with coral reefs. The toxins are ingested by and accumulate in the fishes which when consumed by man ultimately cause ciguatera. Recent advances in toxin pharmacology have identified ciguatoxin as a sodium channel agonist and have begun to address other aspects of ciguatera on the molecular level. Treatment with mannitol relieves the symptoms; the precise mechanism or mechanisms of action have not been proven. Immunoassays are being developed for detecting even negligible amounts of toxins in suspect fish flesh. PMID- 8433405 TI - Computed tomography in fetal methylmercury poisoning. AB - Cerebral computed tomography was studied in eight patients with fetal methylmercury poisoning. All patients had evidence of prenatal exposure to methylmercury and showed psychomotor retardation. All of them had abnormal computed tomography findings. The most common finding was sulcal and ventricular enlargement, with or without cisternal enlargement. These findings indicated generalized cortical and subcortical maldevelopment. The distribution of sulcal and fissural enlargement did not show specific dominance in central sulcus, calcarine fissure or cerebellum. This distribution contrasts with the location of focal atrophy present in adult methylmercury poisoning. The computed tomography findings were relatively mild compared with the clinical features and were not distinct from those in cerebral palsy. PMID- 8433406 TI - Wisteria toxicity. AB - A 50 year-old female ingested 10 seeds from the pods of the Wisteria plant due to curiosity and the perception that they were edible beans. Subsequent toxic effects included headache, gastroenteritis, hematemesis, dizziness, confusion, diaphoresis, and a syncopal episode. She continued to feel tired and complained of being dizzy 5 to 7 days after the ingestion. Despite the abundant references in the literature supporting the toxicity of this plant and the cases cited by Lampe and McCann (1), a literature search identified only one additional case report involving two youths in Italy who ingested at least 5-6 seeds each (2). The three events were sufficiently similar in the onset of the gastrointestinal symptoms and the effects on the central nervous system as to characterize a Wisteria syndrome. PMID- 8433407 TI - Iodoquinol associated seizures and radiopacity. AB - This case report describes seizures and encephalopathy in a nine year-old boy treated with iodoquinol for amebiasis. The toxicity of iodoquinol and other 8 hydroxyquinolines is discussed. The radiopacity of this medication, used worldwide for the treatment of diarrheal illnesses and dermatitis, may be diagnostically useful. PMID- 8433408 TI - Prolonged QT interval and torsade de pointes following astemizole overdose. AB - A 26 year-old woman was admitted to the hospital two hours after astemizole overdose. Electrocardiograph showed a prolonged QT interval. Torsade de pointes occurred 13 h after ingestion. Plasma levels of astemizole plus hydroxylated metabolites showed an apparent plasma half-life of 17 h. The possible occurrence of torsade de pointes in astemizole overdose, and the long elimination time of astemizole and hydroxylated metabolites, makes it necessary to maintain ECG monitoring until QT interval has returned to normal. PMID- 8433409 TI - Infantile chorea following abrupt withdrawal of diazepam and pentobarbital therapy. AB - The acute onset of chorea was seen in a ten week-old male following abrupt cessation of a seven-day course of sedation with diazepam and pentobarbital. These movements slowly resolved over a six-day period and the infant was without neurologic sequelae one week after his chorea resolved. A cerebral MRI was normal. We speculate that the mechanism by which chorea may occur as a withdrawal phenomenon to benzodiazepine/barbiturate treatment is by a functional overactivity of the dopaminergic system in the basal ganglia. PMID- 8433410 TI - A near lethal case of combined strychnine and aconitine poisoning. AB - The successful supportive management of an acute combined strychnine and aconitine poisoning is described. The clinical features including initially resistant ventricular fibrillation and biochemical findings are reported. Occurrence, signs, symptoms, mechanisms of action of both strychnine and aconitine and treatment particularly with regard to the life-threatening arrhythmia induced by aconitine are briefly reviewed. PMID- 8433411 TI - Role of free radicals in toxic hepatic injury. I. Free radical biochemistry. PMID- 8433412 TI - Role of free radicals in toxic hepatic injury. II. Are free radicals the cause of toxin-induced liver injury? PMID- 8433413 TI - Intermediate syndrome: prolonged cholinesterase inhibition. PMID- 8433414 TI - The ocular effects of spitting cobras: I. The ringhals cobra (Hemachatus haemachatus) venom-induced corneal opacification syndrome. AB - Venom from the ringhals cobra (H. haemachatus) caused extensive chemosis, prolonged corneal edema and marked miosis when applied locally to the eyes of two strains of rabbits: Buskat (albino) and Chinchilla (pigmented). In the pigmented rabbits, the corneal edema progressed to complete corneal opacification with corneal and conjunctival neovascularization that remained unchanged until the end of the experiment (70 d). In the albino rabbits the corneal cloudiness and conjunctivitis cleared within three weeks of venom instillation. Treatment with heparin and tetracycline markedly improved the corneal opacification syndrome, while treatment with specific antivenom resulted only in partial improvement. It is postulated that the venom owes its ocular effects to its cardiotoxin, the only venom fraction capable of inducing the corneal opacification syndrome. The protective effect of heparin is probably through its electrostatic binding to the cardiotoxin in the venom. Tetracycline could form ionic bonding at several sites in the strongly basic cardiotoxin. The corneal opacification syndrome was associated with the ability of the snakes to spit since venoms from the other non spitting cobras were devoid of this activity. PMID- 8433415 TI - The ocular effects of spitting cobras: II. Evidence that cardiotoxins are responsible for the corneal opacification syndrome. AB - Fractionation of H. haemachatus, N. nigricollis, N. nivea and N. melanoleuca venoms using Amberlite CG-50 and (NH4)HCO3 elution gradient chromatography yielded 11-13 fractions for each venom. One fraction, F X, from H. haemachatus, two fractions, F X and F XI, from N. nigricollis and one fraction, F VIII, from N. melanoleuca venoms possessed the whole of ocular activity of the venoms. The fractions were the only venom fractions that caused cardiac depressant activity; their effect was reversed by raising Ca++ concentration in the physiological solution; they did not influence the twitches of the phrenic nerve hemidiaphragm and guinea-pig ileum preparations. Further purification of the fractions on Sephadex G-50 followed by fractionation on Amberlite CG-50 yielded fractions free from phospholipase A2 activity but possessing the same ocular effects. Similarly, the cardiotoxin from commercial N. nigricollis venom caused the same ocular effects as the crude venom and its purified cardiotoxic fractions. All cardiotoxic fractions as well as N. nigricollis cardiotoxin, caused extensive chemosis, blepharitis and corneal opacification with corneal and subconjunctival neovascularization. On a weight basis, the cardiotoxins were weaker in their oculotoxic activity than the corresponding parent crude venoms possibly because of the potentiating effect of phospholipase A2 in the crude venoms. It is postulated that in spitting cobras the cardiotoxins are responsible for the corneal opacification syndrome. In other cobra venoms the stable binding of cardiotoxins with acidic proteins limits their possible ocular effects. Only in the venoms of the spitting species are the cardiotoxins present in an appropriately free form to cause the ocular opacification syndrome. PMID- 8433416 TI - Kinetics of amatoxins in human poisoning: therapeutic implications. AB - The kinetics of alpha and beta amanitin were studied in 45 patients intoxicated with Amanita Phalloides. The amatoxins were analyzed by high performance liquid chromatography in plasma (43 cases), urine (35 cases), gastroduodenal fluid (12 cases), feces (12 cases) and tissues (4 cases). All patients had gastrointestinal symptoms and 43 developed an acute hepatitis. Two patients underwent successful liver transplantation. Eight patients, of whom three were children, died. The detection of amatoxins in the biological fluids was time dependent. The first sample was obtained at an average of 37.9 h post ingestion in the patients with positive results and at 70.6 h in the samples without detectable amatoxins. Plasma amatoxins were detected in 11 cases at 8 to 190 ng/mL for alpha and between 23.5 to 162 ng/mL for beta. In 23 cases amatoxins were detected in urine with a mean excretion per hour of 32.18 micrograms for alpha and 80.15 micrograms for beta. In 10 patients the total amounts eliminated in the feces (time variable) ranged between 8.4 and 152 micrograms for alpha amanitin and between 4.2 and 6270 micrograms for beta amanitin. In three of four cases amatoxins were still present in the liver and the kidney after day 5. Amatoxins were usually detectable in plasma before 36 h but were present in the urine until day 4. The rapid clearance indicates that enhanced elimination of amatoxins requires early treatment. Clearance of circulating amatoxins by day 4 spares the transplanted liver. PMID- 8433417 TI - Osmol gaps revisited: normal values and limitations. AB - A study was designed to define the osmol gap in patients whose serum ethanol concentrations are known, to reevaluate several accepted equations for calculating osmolarity, and to apply the results to the theoretical clinical scenario of a toxic alcohol ingestion. The design for the study used consecutive, prospective enrollment of all patients presenting to a large inner city hospital who clinically required determination of their serum ethanol and electrolytes. Three hundred and twenty one consecutive adult patients were enrolled in the study, sixteen were excluded from the final analysis. A stepwise multiple linear regression analysis was performed to determine the best coefficients for sodium, blood urea nitrogen, and ethanol from the data set. Osmolarity was then calculated using these coefficients and traditional models. The osmol gap (measured osmolality minus calculated osmolarity [2*Na + BUN/2.8 + Glu/18 + Etoh/4.6]) was -2 +/- 6 mOsm. Although different equations produced different osmol gaps (ranging from -5 to + 15 mOsm) the standard deviations and correlation coefficients were similar. Large variations exist in the range of osmol gaps. Absolute values are very dependent on the equations used to calculate osmolarity. Because of the larger range of values, small osmol gaps should not be used to eliminate the possibility of toxic alcohol ingestion. PMID- 8433418 TI - Successful donation and transplantation of multiple organs from a victim of cyanide poisoning. AB - Demand for viable human organs for transplantation continues to exceed the supply. To expand supply, the criteria for identification and management of suitable donors must continue to evolve. Poisoned patients are often excluded as potential organ donors due to perceived risks of transmittable agents and/or physiologically compromised organs. In this report, a patient succumbed after an intentional ingestion of cyanide and multiple pharmaceuticals. Donor organ viability was determined by lack of significant injury beyond the central nervous system. Following standard procurement procedures, the heart, liver, corneas, 16 skin grafts and 16 bone grafts were deemed suitable and successfully transplanted. All organ recipients were doing well eight months post transplantation. The focus of procurement personnel should be on tissue injury and not on the mere presence of clinical effect of a toxic agent. With the paucity of organs available, poison centers need to be cognizant of this dilemma when faced with a toxicologically compromised potential organ donor. PMID- 8433419 TI - Vascular surgeons--are they for sale? PMID- 8433420 TI - Crescendo transient ischemic attacks: a surgical imperative. Veterans Affairs trialists. AB - PURPOSE: In a randomized, prospective, multicenter trial at 16 medical centers, 189 of 5000 patients screened with cerebrovascular disease were identified as having angiographic internal carotid artery stenosis (> 50%) corresponding to presenting symptoms of transient ischemic attacks (TIAs), transient monocular blindness, or recent, minor completed stroke. METHODS: Patients were randomly assigned to carotid endarterectomy plus the best medical care (n = 91) versus the best medical care alone (n = 98). RESULTS: After 1 year there was a significant reduction in stroke or crescendo attacks in the 91 patients who received carotid endarterectomy (7.7%) compared with 98 patients who did not undergo operation (19.4%) (p = 0.011). Twelve (12%) of the 98 patients with symptomatic carotid stenosis treated medically had crescendo TIAs, four had minor strokes, and three had major strokes. Crescendo TIAs were defined as disabling, recurrent transient cerebral or retinal ischemia characterized by an increased frequency, duration, or severity of events. The average time from randomization until the onset of crescendo TIAs was 2 months. Seven of the 12 patients in whom crescendo TIAs developed had stenosis greater than 90%, one had greater than 80% stenosis, and four had between 70% and 80% stenosis, with one of these four having contralateral occlusion. Another three patients had 50% or greater contralateral occlusion. Patients with crescendo TIAs were offered carotid endarterectomy, and all 12 had an uncomplicated, urgent procedure. On follow-up the 12 patients were symptom free at the study conclusion. CONCLUSIONS: Crescendo TIAs are disabling symptoms that occur in patients with high-grade carotid stenoses often within 3 months of the initial symptoms of ischemic cerebrovascular disease. The 12% of medically treated patients in whom crescendo TIAs developed had carotid endarterectomy, which abolished symptoms on follow-up. PMID- 8433421 TI - Influence of aspirin in the management of asymptomatic carotid artery stenosis. VA Cooperative Study Group on Asymptomatic Carotid Stenosis. AB - PURPOSE: Aspirin therapy is recommended commonly for symptomatic extracranial carotid artery occlusive disease. However, its role in the management of asymptomatic carotid artery stenosis has not been reported previously. METHODS: In 11 clinical centers during the period 1983 to 1991, 444 adult male patients with significant asymptomatic carotid artery stenosis (> or = 50% arteriographically) were randomized to receive optimal medical management including aspirin plus carotid endarterectomy (n = 211) or optimal medical management alone (n = 233). At the conclusion of the study (mean follow-up time 47.9 months), at the time of a patient's death, or at occurrence of a neurologic end point, 16% of patients (n = 72) were not taking any aspirin, 51% (n = 226) had been converted to receiving enteric-coated aspirin, and only 33% (n = 146) were taking plain aspirin (27% at reduced dosage). Among patients from the medical group, 37 (16%) of 233 were not taking any aspirin and formed the basis for this retrospective analysis of the group for which no control population was available. RESULTS: Mortality rates in this group were not significantly different for patients not taking aspirin as compared with the rates for those taking aspirin, although patients not taking aspirin had a higher incidence of myocardial infarction (27%) as compared with patients taking aspirin (8%), p < 0.05. The incidence of ipsilateral neurologic events for patients not taking aspirin as compared with that for patients who were taking aspirin, respectively, was as follows: stroke, 13.5% and 8.7%, p > 0.05; stroke and transient ischemic attack, 37.8% and 17.3%, p < 0.05. No significant differences were observed in stroke severity scores for patients taking or not taking aspirin. CONCLUSION: These data suggest that patients with significant asymptomatic carotid artery stenosis who are intolerant of aspirin have a higher incidence of neurologic events than those patients able to tolerate the drug. PMID- 8433422 TI - Vascular laboratory cost analysis and the impact of the Resource-Based Relative Value Scale payment system. AB - PURPOSE: This study compares the actual cost of performing noninvasive laboratory studies with reimbursement under the previous Medicare Part B system and under current resource-based relative value scale (RBRVS) guidelines. METHODS: We calculated the cost to operate our own laboratory and estimated national costs for small- and large-model laboratories. Reimbursement under Medicare Part B was calculated for each Current Procedural Terminology code from average Medicare reimbursement allowances and national case volumes in 1990, which were obtained from the Health Care Financing Administration. All data were expressed as dollars per hour of study time to allow universal comparison of costs and reimbursement among tests that require differing lengths of time for completion. RESULTS: Technical costs for laboratory time ranged from $143 to $173 per study hour. The largest components of laboratory expenses were fixed costs, including personnel (37% to 46%), equipment (30% to 42%), and facilities (6% to 8%). Variable costs such as billing (9% to 10%) accounted for most of the remainder. More efficient allocation of equipment resulted in lower costs in large laboratories, whereas continued use of depreciated equipment resulted in lower costs in our own laboratory ($127/hr). CONCLUSIONS: We project that technical reimbursement under RBRVS will be $82/hr nationally and $80/hr locally, whereas global reimbursement (technical plus professional) will be $116/hr and $110/hr, respectively. On the basis of 1990 case volumes, the RBRVS system will decrease national global reimbursement by at least 35% compared with the previous Medicare Part B system. Under the new system, technical reimbursement will decrease by an estimated 27% nationally, whereas professional reimbursement will decrease by 52%. Revenue under RBRVS will not meet the cost to perform studies either nationally or locally. Technical reimbursement is 37% to 54% below actual technical costs, and even global reimbursement is 13% to 34% less than technical costs. Our analysis revealed that costs will exceed reimbursement despite maximization of operating efficiency. This analysis applies to outpatients only. A case mix including inpatients will further reduce reimbursement, because only the professional component is allowed. By setting reimbursement of vascular laboratories below actual costs, the new RBRVS system may ultimately reduce the availability of noninvasive vascular testing for elderly patients. PMID- 8433423 TI - Captopril renal scintigraphy: a new standard for predicting outcome after renal revascularization. AB - PURPOSE: Captopril renal scintigraphy (CRS) is a nuclear medicine technique for evaluating each kidney independently for changes in glomerular filtration rate and perfusion induced by captopril-associated alterations in vascular tone. This study was undertaken to determine the role of CRS in predicting the response to renal revascularization. METHODS: The study group consisted of all patients who underwent preintervention CRS and arteriography, followed by renal revascularization performed between December 1987 and February 1992. After cessation of administration of angiotensin-converting enzyme inhibitors for 48 hours, a standard renogram was obtained, a 50 mg dose of captopril was given, and a second renogram was obtained. A captopril-induced change in the renogram was present when a normal pre-captopril renogram became abnormal after captopril administration. An abnormal baseline scan by definition cannot have a captopril induced change. Blood pressure before revascularization was compared with blood pressure at 3 to 6 months after the procedure according to American Heart Association criteria for hypertension response. RESULTS: Fifty patients received renal revascularization by operation (28 patients) or balloon angioplasty (22 patients). Preoperative captopril-induced changes were present in 29 of the 50 patients. Among the 29 patients with captopril-induced changes, hypertension was cured or improved in 26. When captopril-induced changes were not present, only one of 21 patients improved (p < 0.00001). CONCLUSION: On the basis of these data, CRS appears to reliably predict hypertension response to revascularization in patients with renovascular disease. PMID- 8433424 TI - Ancrod versus heparin for anticoagulation during vascular surgical procedures. AB - PURPOSE: The purpose of this study was to compare the conduct and early results of infrainguinal vascular reconstructions with use of ancrod or heparin for anticoagulation. METHODS: To test the hypothesis that ancrod was an effective alternative to heparin, 28 patients requiring infrainguinal bypass surgery were randomized to receive heparin during operation or ancrod before operation over a period of 12 hours to deplete circulating fibrinogen (0.2 to 0.5 gm/L). RESULTS: No clotting of blood within the grafts or native vessels was noted during the conduct of the surgical procedures in either group. No excessive bleeding was detected during operation in either group. The operative procedure, complication rate, and hospital course were also indistinguishable; patency at 1 month was also equal. CONCLUSION: Fibrinogen depletion with ancrod provides anticoagulation for the conduct of infrainguinal vascular reconstructions that is as effective as heparin. When heparin is contraindicated ancrod is an effective and safe alternative. PMID- 8433425 TI - Interruption of vascular thrombosis by bolus anti-platelet glycoprotein IIb/IIIa monoclonal antibodies in baboons. AB - PURPOSE: Because the platelet membrane receptor glycoprotein IIb/IIIa plays a central role in the recruitment of platelets into forming thrombus, therapeutic inhibition of this receptor complex may be particularly useful to prevent thrombosis after small vessel arterial manipulation. METHODS: The relative hemostatic safety and antithrombotic efficacy for thrombus formation at sites of endarterectomy and implanted prosthetic vascular graft of a murine monoclonal antibody (LJ-CP8) against platelet glycoprotein IIb/IIIa have been determined in baboons after bolus injections in doses (10 mg/kg) that block platelet receptor function for fibrinogen and other adhesive glycoproteins (absent platelet aggregation and bleeding times > 30 minutes without affecting circulating platelet counts). RESULTS: Thrombus formation was eliminated by LJ-CP8 at sites of surgical endarterectomy in fresh segments of homologous aorta incorporated into chronic exteriorized arteriovenous femoral shunts (accumulation of indium 111-labeled platelets fell from 4.40 +/- 0.89 x 10(9) platelets/cm in control animals [n = 6] to 0.23 +/- 0.01 x 10(9) platelets/cm in treated animals [n = 4]; p < 0.005). The formation of thrombus was also abolished by LJ-CP8 at sites of 1 cm prosthetic vascular grafts (4 mm inner diameter polytetrafluoroethylene grafts) interposed into common carotid arteries (deposition of indium 111-labeled platelets decreased from 2.57 +/- 0.43 x 10(9) platelets/cm [n = 5] to 0.16 +/- 0.06 x 10(9) platelets/cm, [n = 4]; p = 0.004). However, LJ-CP8 injections produced substantial bleeding in the surgical wound during the first few hours after operation. Thirty days after operation all four graft implants were patent in JJ-CP8-treated animals compared with two of five in control animals (p = 0.06). CONCLUSIONS: We conclude that profound inhibition of platelet glycoprotein IIb/IIIa receptor function by single bolus injection of LJ-CP8 monoclonal antibody transiently abolishes platelet hemostatic function, eliminates acute thrombus formation at sites of endarterectomy and prosthetic vascular graft implants, and may improve vascular patency. PMID- 8433426 TI - Evaluation of a new treatment strategy for Paget-Schroetter syndrome: spontaneous thrombosis of the axillary-subclavian vein. AB - PURPOSE: The purpose of this study was to evaluate the efficacy of a staged, multimodal algorithm of therapy for durable correction of Paget-Schroetter syndrome. METHODS: Fifty consecutive patients were entered into a sequential treatment program for spontaneous axillary-subclavian vein thrombosis. Forty three had initial thrombolytic or anticoagulant treatment followed by longer-term warfarin sodium therapy. Thirty-six (72%) underwent surgical correction of the underlying structural abnormality, and nine patients had postoperative balloon angioplasty. RESULTS: At the time of final evaluation, 93% of patients with a patent vein and 64% of those with an occluded vein were essentially free of symptoms. After surgical correction there were no episodes of recurrent thrombosis in a mean follow-up period of 3.1 years. Urokinase was the most effective pharmacologic agent for clot lysis (p = 0.003), and restoration of initial patency was the most significant factor in establishing final venous patency determined venographically (p = 0.0003). CONCLUSIONS: It was concluded that a staged, multimodal approach to the Paget-Schroetter syndrome can effectively restore venous patency, reduce rethrombosis, and return normal function. The most effective sequence included transcatheter thrombolytic therapy, 3 months of anticoagulation therapy with warfarin sodium, and transaxillary first rib resection and decompression, followed by balloon angioplasty in cases of residual stricture. PMID- 8433427 TI - Heparin prevents postischemic endothelial cell dysfunction by a mechanism independent of its anticoagulant activity. AB - PURPOSE: Heparin may have protective effects on postischemic vascular endothelial cell function that are distinct from its anticoagulant, antiplatelet, or anticomplement activity. We tested this hypothesis in isolated rat hindlimbs. METHODS: Isolated rat hindlimbs underwent 60 minutes of normothermic ischemia and 10 minutes of reperfusion. Potential heparin interaction with plasma-based proteins or cells was eliminated by perfusion of the hindlimbs with a nonrecirculated albumin-enriched crystalloid buffer. Endothelial function was assessed by measurement of endothelium-derived relaxing factor (EDRF) activity. Limbs perfused at constant pressure were subjected to increasing log dose infusions of acetylcholine and nitroprusside to measure endothelial-dependent (EDRF-mediated) and endothelial-independent vasoreactivity, respectively. Fifty limbs were divided into seven groups: two nonischemic groups (one with heparin) and five ischemia/reperfusion groups treated with increasing doses of heparin (0 to 1.0 U/ml perfusate). RESULTS: The nontreated ischemia/reperfusion group (n = 12) had a 46.2% reduction in endothelial-dependent vasodilation of the rat hindlimb when compared with the nonischemic control (n = 7, p < 0.05). Treatment with heparin 0.5 U/ml (n = 6) nearly abolished this attenuation of endothelial dependent vasodilation (4.3% reduction, p = not significant vs nonischemic control). The endothelial protective effect of heparin was dose-dependent: groups treated with 0.25 U/ml (n = 6) and 0.1 U/ml heparin (n = 7) showed progressive impairment in postischemic EDRF-mediated vasodilation. Endothelial-independent vasodilation induced by nitroprusside was unchanged by ischemia/reperfusion or heparin treatment, which confirmed that the postischemic damage and its protection by heparin were specific to the endothelium. CONCLUSIONS: Heparin prevented postischemic endothelial cell dysfunction by a mechanism independent of its interactions with plasma-based proteins or cells. This nonanticoagulant protective effect may contribute to the salutary effects of heparinization during acute ischemic events. PMID- 8433428 TI - After the blue toe: prognosis of noncardiac arterial embolization in the lower extremities. AB - PURPOSE: To better understand the prognosis of atheroembolic disease, we reviewed the outcomes of 41 patients with embolization to the viscera and lower extremities. METHODS AND RESULTS: All cases involved emboli that originated from a radiographically identified proximal arterial source. There were 30 men and 11 women (mean age 65 years; mean follow-up time 2 years), and all had been first treated for this condition within the past 6 years. The overall mortality rate was 17% (7/41) and the rate of recurrent embolization 15% (6/41). To compare outcomes associated with supradiaphragmatic versus subdiaphragmatic disease, we defined two groups: group 1 comprised patients (n = 5) in whom the identified embolic source extended above the diaphragm, and group 2 comprised patients (n = 36) in whom the source remained below the diaphragm. The mortality rates in groups 1 and 2 were 60% (3/5) and 11% (4/36), respectively (p < 0.05). Recurrent embolization was also significantly higher in group 1 (60% vs 8%, p < 0.025). There were two amputations in group 1 and six in group 2 (p = not significant). Group 2 patients were then divided into two subgroups: those with limited disease (n = 19) in which the emboli had a single, radiographically identified source (i.e., aneurysm or single area of ulcerated plaque) and those with diffuse disease (n = 17) in which the emboli had multiple, radiographically identified potential sources. In the subgroup of patients with limited disease, no deaths or episodes of recurrent embolization occurred, whereas four deaths and three episodes of recurrent embolization occurred in the subgroup of patients with diffuse disease. The differences in these outcomes, however, were not statistically significant. Thirty selected patients (one from group 1 and 29 from group 2) underwent operation on or bypass of the imputed lesion. Only one (7%) of these 30 patients had recurrent embolization. In contrast, recurrent embolization was noted in four (36%) of the 11 patients who did not have an operation directed at the lesion (p < 0.025). No significant difference in mortality was found between patients who underwent operation and those who did not. CONCLUSIONS: Patients with atheroemboli have a substantial mortality rate and risk of recurrent embolization, especially if the disease process extends above the diaphragm; but in selected patients, operation may decrease the frequency of recurrence without increasing mortality. PMID- 8433429 TI - Descending thoracic aorta-to-femoral artery bypass: ten years' experience with a durable procedure. AB - PURPOSE: Arterial bypass from the descending thoracic aorta to the femoral system provides successful perfusion when an approach to the abdominal aorta is undesirable. This review of a large series with a decade of experience was conducted to better define patency data and the natural history of patients after this operation. METHODS: During a 10-year period, 21 patients, 18 men and 3 women (mean age 57 years), underwent descending thoracic aorta to left femoral artery bypass with femorofemoral bypass. These were placed to convert axillopopliteal or axillofemoral grafts (12 patients) to a more permanent inflow source. The axillary bypasses had been previously placed to allow removal of infected aortic grafts and had undergone a total of 14 revisions or thrombectomies before conversion. In addition, patients had this procedure after multiple failed attempts (at least two) at intraabdominal aortic repair (five patients) or to avoid exploration of the abdomen after extensive retroperitoneal dissection or radiation (four patients). Surgical technique involved a seventh interspace thoracotomy with a transdiaphragmatic retroperitoneal anterior axillary line tunnel to the left groin. RESULTS: There was no perioperative mortality. The mean hospital visit was 15.1 days and intensive care stay 4.3 days. There was no perioperative myocardial infarction, stroke, or renal failure that necessitated dialysis. With a follow-up period of 1 to 121 months (mean 44), the 4-year patency rate was 100%. A single graft failed at 49 months but was renewed by thrombectomy and femorofemoral bypass. Thus the extended patency rate was 86%, but the secondary patency rate remained 100% throughout. Since the thoracic operations, patients have required five femoropopliteal, three femorotibial, two profunda, and two femorofemoral operations. CONCLUSIONS: Descending thoracic aorta-to-femoral artery grafting is a safe, extremely durable arterial bypass configuration. It is an excellent reconstruction for survivors of aortic graft infection, those who have had multiple failures of aortic grafts, and patients for whom abdominal exploration would be hazardous. PMID- 8433430 TI - In situ allograft replacement of infected infrarenal aortic prosthetic grafts: results in forty-three patients. AB - PURPOSE: Dissatisfaction with conventional methods of treatment of infected infrarenal aortic prosthetic grafts and excellent long-term results reported by heart surgeons after allograft replacement for management of infections involving the ascending aorta have prompted us to investigate allograft replacement in the management of arterial infections. METHODS: From October 1988 to April 1992, 43 consecutive patients with infected infrarenal aortic prosthetic grafts underwent in situ replacement with preserved allografts obtained from cadavers as part of a program to retrieve multiorgan transplant tissue. Thirty-four patients had isolated prosthetic infections, whereas nine had aortoenteric fistulas. One patient had a concomitant below-knee amputation for septic arthritis of the ankle as a result of septic emboli. Nineteen patients had nonvascular-associated procedures, including 17 intestinal procedures. RESULTS: Five patients (12%) died after operation: four of general causes and one of rupture of the native aorta as a result of persistent infection. Three patients successfully underwent repeat operation for allograft-related complications (one case each of occlusion, septic rupture, and graft-enteric fistula). All surviving patients were discharged after control angiography showed patent allografts. Two patients were unavailable for follow-up. The other 36 patients have been monitored with serial duplex and computed tomography scanning for a mean follow-up of 13.8 months (range 1 to 42 months). There were four late deaths: three were unrelated to the vascular operation, and one may have been caused by late persistent or recurrent infection. Nine patients (26%) have had pathologic changes in the allograft, with three (9%) requiring repeat operation. There were no early or late postoperative amputations in the entire series. CONCLUSIONS: Although complete protection against persistent or recurrent infection has not been achieved and late deterioration may be expected, in situ allograft replacement seems to be a major advance in the management of infected infrarenal aortic prosthetic grafts. PMID- 8433431 TI - Experience with 1509 patients undergoing thoracoabdominal aortic operations. AB - PURPOSE: The purpose of this study was to retrospectively identify variables associated with early death and postoperative complications in patients undergoing thoracoabdominal aortic operations. METHODS: The data on 1509 patients who underwent 1679 thoracoabdominal aortic repairs between 1960 and 1991 were retrospectively reviewed. The median age was 66 years (range 1.5 years to 86 years), and aortic dissection was present in 276 (18%) patients. The extent of the first repair performed included 378 (25%) type I (proximal descending to upper abdominal aorta), 442 (29%) type II (proximal descending aorta to below the renal arteries), 343 (23%) type III (distal descending and abdominal aorta), and 346 (23%) type IV (most of the abdominal aorta). The median total aortic clamp time was 43 minutes. RESULTS: The 30-day survival rate was 92% (1386/1509) for the 30-year period. On multivariate analysis the preoperative and operative variables associated with death included (p < 0.05) increasing age, preoperative creatinine level, concurrent proximal aortic aneurysms, coronary artery disease, chronic lung disease, and total aortic clamp time. When the postoperative variables were also included in the stepwise logistic regression model, then in addition, cardiac complications, stroke, kidney failure, and gastrointestinal hemorrhage became significant (p < 0.05). The overall incidence of paraplegia or paraparesis was 16% (234/1509). By use of stepwise logistic regression analysis, the significant predictors (p < 0.05) of paraplegia or paraparesis developing were total aortic clamp time, extent of aorta repaired, aortic rupture, patient age, proximal aortic aneurysm, and history of renal dysfunction. Kidney failure (postoperative creatinine level > 3 mg/dl or dialysis) occurred in 18% (269/1509) of patients; dialysis was required in 9% (136/1509). Gastrointestinal complications manifested in 7% (101/1509) of patients. CONCLUSION: Although the survival rate has improved, paraplegia/paraparesis and kidney failure continue to be vexing problems that require further research. PMID- 8433432 TI - Adventitial elastolysis is a primary event in aneurysm formation. AB - PURPOSE: Adventitial elastin degradation is a hallmark of abdominal aortic aneurysm (AAA) formation in human beings, although the quantitative relationship between elastin loss and AAA formation and growth is unknown. This study was undertaken to quantitate the reduction of adventitial elastin for small AAA, to determine whether the loss of this structural component parallels aneurysm growth, and to examine the ultrastructure of the remaining elastin elements. METHODS: Longitudinal strips of anterior aneurysm wall were taken from 12 patients having elective repair of small (diameter < 5 cm, n = 4), moderate (diameter < 5 to 7 cm, n = 4), or large (diameter > 7 cm, n = 4) AAA and from six normal control subjects at autopsy. Specimens were prepared with elastin and collagen stains for histologic examination or formic acid for scanning electron microscopic evaluation of elastin architecture. Adventitial elastin content of aneurysmal and control aortas was quantitated with video microscopy and compared by aneurysm diameter. RESULTS: The inner portion of adventitia of normal aortic wall was composed of densely compacted alternating lamellae of elastin and collagen, which were grossly disrupted in all aneurysms. The remaining elastin fibers were disorganized and tortuous. There was an 81.6% +/- 2.1% reduction in elastin lamellae and an 85.7% +/- 4.2% reduction in fibers per lamellae compared with the number in control aortas (p < 0.001). Size of the aneurysm made no difference in adventitial elastin content. CONCLUSION: These data strongly suggest that elastolysis is a primary event in AAA formation that occurs before over loss of adventitial structural integrity and the development of small aneurysms. PMID- 8433433 TI - Comparison of angioscopy and angiography for monitoring infrainguinal bypass vein grafts: results of a prospective randomized trial. AB - PURPOSE: This study was designed to determine whether, in primary infrainguinal bypass grafts in which only saphenous vein is used as the graft conduit, routine monitoring with intraoperative angioscopy can improve early graft patency as compared with standard monitoring with intraoperative completion angiography; and to delineate the advantages and disadvantages of these two modalities and their respective roles for the routine monitoring of the infrainguinal bypass graft. METHODS: A total of 293 patients undergoing primary saphenous vein infrainguinal bypass grafting were prospectively randomized and monitored with either completion angioscopy or completion angiography. Clinical parameters, indications for operation, graft anatomy, and configuration were evenly matched in both groups. Forty-three bypasses were excluded from the study after randomization, including 12 veins randomized to angiogram, deemed inferior, and prepared with angioscopy. RESULTS: In the 250 bypass grafts (angioscopy 128, angiography 122) there were 39 interventions (conduit, 29; anastomosis, 8; distal artery, 2), 32 with angioscopy and 7 with angiography (p < 0.0001). Twelve (4.8%) of the 250 grafts failed in less than 30 days, four (3.1%) of 128 in the angioscopy group and eight (6.6%) of 122 in the angiography group (p = 0.11 by one-sided hypothesis test). CONCLUSION: Although no statistical improvement in the proportions of failures in primary saphenous vein bypass grafts routinely monitored with completion angioscopy rather than the standard completion angiogram was demonstrated, the study delineates a trend that favors completion angioscopy for routine vein graft monitoring and demonstrates the advantages of angioscopy in preparing the optimal vein conduit. PMID- 8433434 TI - Complications of missed arterial injuries. AB - PURPOSE: The natural history of untreated major injuries is not well known, although serious complications are seen. The follow-up of patients who have trauma is often incomplete, and this study was undertaken to evaluate the nature of these wounds. METHODS: Thirty-one patients with missed major arterial wounds were examined and treated according to the pathologic condition encountered. All had been seen at other hospitals, some on more than one occasion, and then sought assistance for continued problems. RESULTS: There were 16 aneurysms in 31 patients: 4 arteriovenous fistulas, 4 dissections, 3 thromboemboli, and 1 stenosis. The arteries included the following: carotid 12, aorta 5, femoropopliteal 8, subclavian 2, axillary 1, innominate 1, iliac 1, and tibial 1. Three patients had a stroke, one had a transient ischemic attack, two had leg ischemia, and one had a gangrenous foot. Operation was required in 27 patients; there were no deaths. CONCLUSIONS: Transmural traumatic arterial wounds of major vessels can result in serious delayed complications, months or even years after the injury. False aneurysms, dissections, occlusions, and fistulas in the extremities may not be lethal, but they cause significant disability. Such lesions in the neck or trunk are more dangerous. Despite the inconvenience and expense, patients with injuries of major arteries are best served by early repair of the wound. PMID- 8433435 TI - Isolated limb perfusion with urokinase for acute ischemia. AB - PURPOSE: Isolated limb perfusion with urokinase was used to salvage an acutely ischemic lower limb. METHODS: Isolated limb perfusion with urokinase over a 90 minute period was used in the treatment of a 69-year-old female patient with acute ischemia of the left leg after thrombosis of a femoral artery bypass graft. Previous balloon embolectomy and heparin therapy had failed. The flow rate was able to be increased progressively without rise in the line pressure during the course of the perfusion, indicating an increase in capacity of the peripheral arterial bed. Fibrinogen and plasminogen levels in the isolated circulation remained low throughout the perfusion. The concentration of cross-linked fibrin degradation particles (d. dimer) rose progressively in the isolated circulation but remained at normal levels in the systemic circulation during perfusion. RESULTS: Completion angiography demonstrated clearance of thrombus in the popliteal artery and appearance of arteries not seen on preperfusion films. Clinical improvement paralleled the angiographic appearances, with restoration of limb viability. CONCLUSION: We concluded that isolated limb perfusion with use of urokinase is safe and worthy of further investigation. PMID- 8433436 TI - The relation of venous ulceration with ambulatory venous pressure measurements. AB - Two hundred thirty-six limbs of 220 unselected patients who were admitted with venous problems (83 with ulcers) were studied with continuous-wave Doppler ultrasonography, duplex scanning, and ambulatory venous pressure measurements. Patients with evidence of deep venous disease because of reflux or obstruction in the deep veins on Doppler and duplex ultrasonic examination or with an ambulatory venous pressure greater than 45 mm Hg despite the ankle cuff had venography. One hundred fifty-three limbs had superficial venous disease (reflux in the superficial veins with competent popliteal valves), and 83 limbs had deep venous disease (popliteal reflux on duplex examination or deep venous obstruction on venography). No ulceration occurred in limbs with ambulatory venous pressure < 30 mm Hg, and there was a 100% incidence with ambulatory venous pressure > 90 mm Hg. A linear increase occurred from 14% in limbs with ambulatory venous pressure between 31 and 40 mm Hg to 100% in limbs with ambulatory venous pressure greater than 90 mm Hg (r = 0.79). In the groups studied, an increased incidence of ulceration was associated with an increase in ambulatory venous pressure irrespective of whether the venous problem was the result of superficial or deep venous disease. Ambulatory venous pressure has both diagnostic and prognostic significance in patients with venous disease. PMID- 8433437 TI - Ruptured mesenteric artery aneurysm in a patient with alpha 1-antitrypsin deficiency: etiologic implications. AB - Clinical observations suggest that some aneurysms may be manifestations of intrinsic tissue abnormalities or systemic disease. Several investigators have reported reduced elastin content and increased elastase activity in infrarenal aortic aneurysms. Alpha 1-antitrypsin is the primary serum protease inhibitor modulating elastase activity. Elevated elastase activity caused by reduced alpha 1-antitrypsin inhibition, theoretically, could contribute to aneurysm formation. We report a case of ruptured middle colic artery aneurysm in a patient with multiple visceral artery aneurysms and profound alpha 1-antitrypsin deficiency. Reported middle colic artery aneurysms are reviewed, and etiologic implications are discussed. PMID- 8433438 TI - The 5th Annual Meeting of the American Venous Forum. Orlando, Florida, February 24-26, 1993. Abstracts. PMID- 8433439 TI - Ruptured abdominal aortic aneurysms: should repair ever be denied? PMID- 8433440 TI - Primary venous leiomyosarcoma: a rare but lethal disease. PMID- 8433441 TI - Pathologic confirmation of the principles of the thromboexclusion operation for descending aortic dissection. PMID- 8433442 TI - Inferior vena cava leiomyosarcoma. PMID- 8433443 TI - Cryopreserved saphenous vein allogeneic homografts. PMID- 8433444 TI - Protecting boxers who won't quit. PMID- 8433445 TI - Magnetic resonance spectroscopy may offer early look at HIV disease-mediated changes in brain. PMID- 8433446 TI - Obtaining drug for AIDS-related toxoplasmosis. PMID- 8433447 TI - With fetal tissue moratorium lifted, applications begin reaching National Institutes of Health. PMID- 8433448 TI - From the Centers for Disease Control and Prevention. Preliminary report: foodborne outbreak of Escherichia coli O157:H7 infections from hamburgers- Western United States, 1993. PMID- 8433449 TI - From the Centers for Disease Control and Prevention. Emergency public health surveillance in response to food and energy shortages--Armenia, 1992. PMID- 8433450 TI - From the Centers for Disease Control and Prevention. Influenza activity--United States, 1992-93. PMID- 8433451 TI - From the Centers for Disease Control and Prevention. Gang-related outbreak of penicillinase-producing Neisseria gonorrhoeae and other sexually transmitted diseases--Colorado Springs, Colorado. PMID- 8433452 TI - From the Centers for Disease Control and Prevention. Differences between anonymous and confidential registrants for HIV testing--Seattle, 1986-1992. PMID- 8433453 TI - From the Centers for Disease Control and Prevention. Approaches to improving adherence to antituberculosis therapy. PMID- 8433454 TI - From the Centers for Disease Control and Prevention. Coccidioidomycosis--United States, 1991-1992. PMID- 8433455 TI - Promoting primary care: where to start? PMID- 8433456 TI - Promoting primary care: where to start? PMID- 8433457 TI - Promoting primary care: where to start? PMID- 8433458 TI - Is justification of animal research necessary? PMID- 8433460 TI - Is justification of animal research necessary? PMID- 8433459 TI - Is justification of animal research necessary? PMID- 8433461 TI - Is justification of animal research necessary? PMID- 8433462 TI - Mandatory testing for HIV. PMID- 8433463 TI - Mandatory testing for HIV. PMID- 8433464 TI - Mandatory testing for HIV. PMID- 8433465 TI - Weight cycling and mortality: support from animal studies. PMID- 8433466 TI - Staging procedures, clinical management, and survival outcome for ovarian carcinoma. AB - OBJECTIVE: To evaluate the relationship between survival and patterns of clinical management for ovarian carcinoma. DESIGN: Retrospective analysis of cancer registry data including follow-up, operative reports, and pathology reports. SETTING: Seventy-seven Illinois hospitals with active cancer registries. PATIENTS: A total of 2669 women with newly diagnosed ovarian carcinoma from 1983 through 1988. MAIN OUTCOME MEASURES: Frequency of use of specific staging procedures and treatment options. Survival was estimated using the Kaplan-Meier product-limit method. RESULTS: Thirty percent of 632 stage I patients, 31% of 233 stage II patients, and 45% of 516 stage III patients underwent hysterectomy, bilateral salpingo-oophorectomy, omentectomy, sampled peritoneal washings, and node biopsy. Five-year survival for those receiving this extensive surgery (who were therefore pathologically staged) was as follows: stage I, 80%; stage II, 63%; and stage III, 28%. For those not receiving this extensive surgery (who were therefore clinically staged), the 5-year survival at these stages was 76%, 62%, and 21%, respectively. The overall survival curves were not significantly different between those who were pathologically staged and those who were clinically staged for stage I patients (P = .27) or stage II patients (P = .47), but were for stage III patients (P = .01). Platinum-based combination chemotherapy was given to 76% of 221 patients with pathological stage III disease. Their 5-year survival--50% for the group with no residual disease and 20% for the group with residual disease--was better than for those receiving regimens without platinum--37% and 5%, respectively, for the two groups--and the overall survival curves were significantly better for those receiving platinum (P < .0005 for both groups). The groups receiving platinum had younger patients. CONCLUSIONS: Extensive surgery for pathological staging was not usually done for management of ovarian cancer, while platinum-based chemotherapy was commonly used. Failure to undergo extensive surgery had little impact on survival for stage I and II patients. However, use of extensive surgery and platinum-based chemotherapy improved survival for stage III patients. The improved survival for this group receiving platinum-based chemotherapy may be explained in part by selection of younger patients for this treatment. PMID- 8433467 TI - Prospective study of serum CA-125 levels as markers of ovarian cancer. AB - OBJECTIVE: To evaluate prospectively the sensitivity and specificity of serum CA 125 levels for the detection of ovarian cancer. DESIGN: Case-control study nested within a cohort of women who donated blood to a community-based serum bank established in 1974. SETTING: Washington County, Maryland. POPULATION: Cases consisted of 37 women who developed ovarian cancer from 1975 through 1989. Controls consisted of 73 women, matched on age and time since last menstrual period, and free of cancer until the cases' diagnoses. STUDY VARIABLE: Serum CA 125 levels. OUTCOME MEASURE: Histologically confirmed ovarian cancer. RESULTS: Levels of serum CA-125 among cases were higher than among controls for each 3 year interval up to 12 years prior to the time of the cases' diagnoses. The median level for cases diagnosed within the first 3 years of follow-up was 35.4 U/mL compared with 9.0 U/mL for controls (P = .002). The sensitivity of a serum CA-125 level greater than 35 U/mL within the first 3 years was 57% (95% confidence interval, 20% to 88%) and the specificity was 100% (95% confidence interval lower limit, 73%). Sensitivity and specificity decreased with increasing time to diagnosis. CONCLUSIONS: Measurement of serum CA-125 levels, particularly at a reference value of 35 U/mL, is not sufficiently sensitive to be used alone as a screening test for the detection of ovarian cancer. Lower CA-125 reference values could identify women at higher risk of developing ovarian cancer, but CA 125 measurement cannot be recommended for this purpose because of the high proportion of women who would be falsely classified as being at high risk for developing ovarian cancer. PMID- 8433468 TI - Decision rules for the use of radiography in acute ankle injuries. Refinement and prospective validation. AB - OBJECTIVE: To validate and refine previously derived clinical decision rules that aid the efficient use of radiography in acute ankle injuries. DESIGN: Survey prospectively administered in two stages: validation and refinement of the original rules (first stage) and validation of the refined rules (second stage). SETTING: Emergency departments of two university hospitals. PATIENTS: Convenience sample of adults with acute ankle injuries: 1032 of 1130 eligible patients in the first stage and 453 of 530 eligible patients in the second stage. MAIN OUTCOME MEASURES: Attending emergency physicians assessed each patient for standardized clinical variables and classified the need for radiography according to the original (first stage) and the refined (second stage) decision rules. The decision rules were assessed for their ability to correctly identify the criterion standard of fractures on ankle and foot radiographic series. The original decision rules were refined by univariate and recursive partitioning analyses. MAIN RESULTS: In the first stage, the original decision rules were found to have sensitivities of 1.0 (95% confidence interval [CI], 0.97 to 1.0) for detecting 121 maleolar zone fractures, and 0.98 (95% CI, 0.88 to 1.0) for detecting 49 midfoot zone fractures. For interpretation of the rules in 116 patients, kappa values were 0.56 for the ankle series rule and 0.69 for the foot series rule. Recursive partitioning of 20 predictor variables yielded refined decision rules for ankle and foot radiographic series. In the second stage, the refined rules proved to have sensitivities of 1.0 (95% CI, 0.93 to 1.0) for 50 malleolar zone fractures, and 1.0 (95% CI, 0.83 to 1.0) for 19 midfoot zone fractures. The potential reduction in radiography is estimated to be 34% for the ankle series and 30% for the foot series. The probability of fracture, if the corresponding decision rule were "negative," is estimated to be 0% (95% CI, 0% to 0.8%) in the ankle series, and 0% (95% CI, 0% to 0.4%) in the foot series. CONCLUSION: Refinement and validation have shown the Ottawa ankle rules to be 100% sensitive for fractures, to be reliable, and to have the potential to allow physicians to safely reduce the number of radiographs ordered in patients with ankle injuries by one third. Field trials will assess the feasibility of implementing these rules into clinical practice. PMID- 8433469 TI - Clinical utility and cost-effectiveness of an air suspension bed in the prevention of pressure ulcers. AB - OBJECTIVE: To determine, in critically ill patients at risk, both the clinical utility and cost-effectiveness of using an air suspension bed in the prevention of pressure ulcers. DESIGN: Randomized, parallel group, controlled clinical trial with accompanying cost-effectiveness analysis. SETTING: 30-bed multidisciplinary intensive care unit. PATIENTS: 100 consecutive patients at risk for the development of pressure ulcers randomly assigned to receive treatment on either an air suspension bed or a standard intensive care unit bed. Patients considered at risk were those at least 17 years of age with an Acute Physiology and Chronic Health Evaluation II (APACHE II) score greater than 15 who had an expected intensive care unit stay of at least 3 days. MAIN OUTCOME MEASURES: The development of pressure ulcers by site and severity and the costs associated with each of the two programs. RESULTS: The air suspension bed was associated with fewer patients developing single, multiple, or severe pressure ulcers. In patients at risk, the use of an air suspension bed in the prevention of pressure ulcers was a cost-effective therapy. CONCLUSIONS: Despite intense nursing care, pressure ulcers are more prevalent in the critically ill patient population than in the general hospital population. Air suspension therapy provides a clinically effective means of preventing pressure ulcers in these patients. In patients at risk, air suspension therapy was a cost-effective means of managing pressure ulcers compared with the standard hospital bed. PMID- 8433470 TI - Preventive health care for adults with HIV infection. AB - OBJECTIVE: To assess the level of evidence for preventive health interventions for adults with human immunodeficiency virus (HIV) infection. DATA SOURCES: A MEDLINE literature search for each intervention, supplemented by reviewing conference proceedings and the recommendations of experts. STUDY SELECTION: English-language studies of interventions that contribute to one of the following goals were reviewed: (1) prevention of complications of HIV infection; (2) early detection of complications, before symptoms develop, at a stage in which early treatment could lead to improved outcome; (3) slowing of HIV disease progression; (4) reduction in the risk of transmission of infectious agents, such as HIV itself; and (5) prevention of psychological distress and improvement in the quality of life. DATA EXTRACTION: The importance of interventions and quality of supporting evidence were evaluated using criteria modified from the US Preventive Services Task Force. DATA SYNTHESIS: Existing evidence strongly supports the efficacy of some preventive measures: primary and secondary Pneumocystis carinii pneumonia prophylaxis; secondary prophylaxis of Cryptococcus, Toxoplasma, and cytomegalovirus infections; tuberculin testing, with chemotherapy for individuals with positive test results; syphilis screening; Papanicolaou tests; educational measures to reduce the transmission of HIV and other infections; T-lymphocyte monitoring; and antiretroviral therapy in selected patients. Recommended measures of possible, but less certain, effectiveness include vaccines to prevent influenza, Haemophilus influenzae, pneumococcal, and hepatitis B infections; prophylaxis for recurrent esophageal and vaginal candidiasis; primary prophylaxis of Mycobacterium avium complex; tuberculosis prophylaxis for anergic, high-risk individuals; routine physical examination; screening for gonorrhea and Chlamydia in high-risk women; monitoring Toxoplasma titers, complete blood cell counts, and serum chemistry values; attempting to maintain weight through nutritional interventions; and exercise. Mental health and substance abuse interventions are probably very important, but documentation of their benefits is limited. Some measures require further study before they can routinely be recommended, including vitamin and mineral supplementation; specific nutritional diets; and laboratory tests, other than CD4 counts, for monitoring disease progression. CONCLUSIONS: Persons with HIV infection have different stage-specific health maintenance needs that form an important part of comprehensive care for people in all stages of infection. PMID- 8433471 TI - Clinical heterogeneity among patients with Gaucher's disease. PMID- 8433472 TI - The metamorphosis of medical ethics. A 30-year retrospective. PMID- 8433473 TI - Ovarian cancer. PMID- 8433474 TI - A new partnership for change. PMID- 8433475 TI - Acting for patients. PMID- 8433476 TI - Choosing a specialty: a guide for students. PMID- 8433477 TI - It's not the end of the world. PMID- 8433478 TI - A piece of my mind. Jerico Springs, Missouri. PMID- 8433479 TI - [Intraoperative delayed pneumothorax after subclavian vein catheterization]. AB - Intraoperative delayed pneumothorax occurred in five patients. It took several attempts to insert a subclavian vein catheter in four of the patients. The first chest X-ray films after the insertion of the catheter in the five patients were not indicative of pneumothorax. Pulse oximetry could detect the initial sign of pneumothorax prior to hemodynamic instability in three patients. In case of positive pressure ventilation and nitrous oxide administration for general anesthesia, this complication may be life threatening. It is necessary to take great care not to overlook intraoperative delayed pneumothorax in a patient with subclavian vein catheterization. PMID- 8433480 TI - [Two cases of anaphylactoid reactions after intravenous methylprednisolone sodium succinate administration]. AB - We have experienced two cases of anaphylactoid reactions following intravenous methylprednisolone sodium succinate administration. They had neither asthmatic nor other allergic histories. The first case was a 45-yr-old man. In addition to the antigenicity of hydrocortisone itself, it is suggested that administration speed was so fast that its side effects were intensified. The second case was a 10-yr old girl. Succinate ester was thought to be the cause of her allergic reaction (urticaria). It is also possible that her hypersensitivity to steroids was dose-dependent. PMID- 8433481 TI - [A critical patient relieved from status asthmaticus with isoflurane inhalation therapy]. AB - In cases of life-threatening status asthmaticus which are refractory to drug therapy, the administration of inhalation anesthetics can be life-saving as they help alleviate bronchial spasm. We had an 11-year-old female patient suffering from status asthmaticus who was moribund from severe CO2 narcosis and was not responding to any of the conventional therapies. She finally fell into ventricular fibrillation. After cardiopulmonary resuscitation, we administered 2.0% isoflurane in oxygen. Within half an hour, her high inspiratory pressure was dramatically decreased, and then the isoflurane concentration was maintained at 1.0%. After 14 hours of isoflurane anesthesia, PaCO2 decreased to the normal level and the isoflurane treatment was discontinued. The endotracheal tube was removed 4 hours later. She had an uneventful recovery and was discharged from the hospital 11 days later. With its low metabolic rate and therefore low organ toxicity, as well as its low arrhythmogenicity with remarkable bronchodilating activity, we feel isoflurane may well be superior to other inhalation anesthetics in the treatment of status asthmaticus. PMID- 8433482 TI - [Effect of the prone position on ICG excretion during normotensive or hypotensive isoflurane anesthesia]. AB - We evaluated the effect of prone position on ICG excretion during normotensive and hypotensive isoflurane anesthesia. In supine position, either normotensive or hypotensive anesthesia produced no significant prolongation in ICG excretion. In prone position, however, both normotensive and hypotensive anesthesia caused a significant prolongation in the excretion. The results suggest that prone position decreases the hepatic blood flow or hepatic function during isoflurane anesthesia. PMID- 8433483 TI - [Postoperative apnea in preterm infants after inguinal herniorrhaphy]. AB - Preterm infants may become apneic during immediate postoperative period. We studied prospectively postoperative apneic attack in 167 preterm infants after inguinal herniorrhaphy with nitrous oxide-halothane anesthesia. Their mean gestational age was 30 +/- 3 weeks. The mean postnatal age at operation was 14 weeks. The post-conceptual age varied between 36 and 56 weeks. The mean birth weight was 1351 +/- 395 kg. Although many of them had a risk factor of postoperative apneic attack, i.e.a young post-conceptual age (less than 41 weeks), a light weight at operation (below 3000g), only one infant who had received emergency operation had an episode of apneic attack up to 2 postoperative days. For preventing postoperative apneic attack in preterm infants after inguinal hernia, we recommend the use of halothane anesthesia and the attention until a complete awakening. PMID- 8433484 TI - [A case of radiculitis induced by spinal cord electrical stimulation by a percutaneously inserted needle]. AB - Spinal cord electrical stimulation was performed by a percutaneously inserted needle for causalgia of the right upper limb. The end of electrode was positioned along a line extending down the 5th vertebral body in the vicinity of the right 6th cervical nerve root, after which it was permanently implanted following confirmation of desensitizing effects. Although the patient later returned to normal life without requiring any ancillary medication, beginning after a period of roughly six months, the pain suddenly began to increase when stimulated. When stimulated by extracting the electrode 1 cm under fluoroscopic guide, the irritation was relieved somewhat. As radiculitis of 6th cervical nerve was suspected, selective radicular block of 6th cervical nerve was performed. After selective radicular block, the patient's complaint diminished. Based on the above findings, we consider that the physical stimulation caused by the electrode in contact with the nerve root brought about inflammation of the 6th cervical nerve root. This patient was then treated by removing the causative stimulation and selective radicular block of affected nerve, the details of which are reported. PMID- 8433485 TI - [Utilization of Lotus 1-2-3 for on-line data logging system from clinical monitors]. AB - We contrived to obtain digital output data from clinical monitors using "Lotus 1 2-3" and its on-line data logging add-in software "1-2-3 DataLogger". Easy macroprogramming of Lotus 1-2-3 enabled us to obtain digital data automatically into the worksheet of Lotus 1-2-3 from the monitors. Data taken up into the worksheet could be analysed readily using graphic function or calculation of Lotus 1-2-3. PMID- 8433486 TI - [Evaluation of the efficacy of a leukocyte depletion filter]. AB - We evaluated the efficacy of a leukocyte depletion filter (Pall RC 100) during operation. Clinically necessary blood was transfused to replace blood loss during the operation. Kinds of transfused blood and speed of transfusion were selected by clinical need. One leukocyte depletion filter was used at most for 4 units of transfused pack (200 ml). Blood samples were taken before and after the filtration to measure white blood cell (WBC), red blood cell (RBC), platelet and hematocrit. Blood samples before filtration and after filtration with white blood cell excluded, were examined by automated hematology analyzer (Coulter counter). White blood cell after filtration was counted by the hemacytometer method using Hauser chamber. The method of multiple linear regression was applied in order to estimate the removal rate of WBC and recovery rate of RBC. The independent variables were categorized in the following 3 sets: the age of transfused blood (day), duration of transfusion (min) and transfused volume (ml). Removal rates of WBC when 1, 2, 3 or 4 units were passed per filter, were 99.99% +/- 0.028%, 99.89% +/- 0.224%, 99.12% +/- 1.519% and 97.81% +/- 2. 866%, respectively. Removal rate of WBC when 4 units were passed per filter, was significantly lower compared with the rate when fewer units were passed. Recovery rates of RBC when 1, 2, 3, or 4 units were passed per filter, were over 99.5%, and there were no significant differences among 4 examined points. Only three variables, the age of transfused blood, duration of transfusion and transfused volume, showed a significant correlation with the removal rate of WBC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433487 TI - [Can ozone administration activate the tissue metabolism?--A study on brain metabolism during hypoxic hypoxia]. AB - As it was thought that the tissue metabolism could be activated by administration of ozone, the influence of ozone on cerebral metabolism was studied under hypoxic condition. Ozone 1.5% was obtained from an ozonizer which separates the ozone from oxygen. Objects were 30 mature rabbits and they inhaled 3% oxygen in 97% nitrogen (PaO2 17-19 mmHg) by spontaneous respiration through a tracheostomy cannula. Objects were divided into three groups. Control rabbits inhaled only anoxic gases without ozone administration. Although the oxygen group also inhaled anoxic gases, pure oxygen was administered through an A-V shunt, previously made on femoral artery and vein, with an oxygenator, named Nichidai style (counter current-exchange method). Similarly, the ozone group was given ozone with the oxygenator via A-V shunt. In each group, survival time as well as ATP, ADP, AMP and lactic acid lipo-peroxide in brain were examined. After the administration of ozone, survival time was prolonged significantly, compared with the control group (P < 0.005). Equally, ATP and energy charge in the brain were well maintained (P < 0.005) and the lactate production was inhibited significantly (P < 0.005). These results indicate that oxidizing effect of ozone will be beneficial to maintain energy charge in brain tissue during hypoxia. Further, ozone might activate the energy metabolism in animal tissues. PMID- 8433488 TI - [Effect of succinylcholine on serum potassium concentration in children with chronic renal failure]. AB - Serum potassium (K+) levels were measured after intravenous injection of succinylcholine (SCh) in 10 children with chronic renal failure, 10 normal children aged 1 to 10 years and 10 children with chronic renal failure after pretreatment with pancuronium prior to SCh. Arterial blood gas was maintained within normal ranges. The serum K+ level increased significantly during 10 minutes after SCh in normal children. There was no significant difference between serum K+ levels in normal children and those in children with chronic renal failure. Administration of pancuronium in small doses (20 micrograms.kg-1) prior to SCh (1 mg.kg-1) was not effective to prevent serum K+ elevation completely. Our results indicate that the administration of SCh in children with chronic renal failure might be possible without increasing serum potassium level. PMID- 8433489 TI - [A microelectrode study of the antagonism of d-tubocurarine induced neuromuscular blockade by edrophonium and neostigmine]. AB - It has been reported clinically that edrophonium (EDR) has a more potent antagonistic effect on the fade of twitch tension and a less potent antagonistic effect on the depressed single twitch force induced by muscle relaxants than does neostigmine (NST). However, the details of the mechanism have not yet been clarified. In this experiment, to compare the antagonistic effect of EDR and NST on the neuromuscular blocking effect of dTc, the recovery from dTc induced neuromuscular blocking effect on both the postjunctional membrane and the motor nerve terminal with EDR or NST was studied using intracellular recording techniques in rat phrenic nerve-hemidiaphragm preparations. The preparation was constantly perfused with physiological saline solution at room temperature. To determine the ACh sensitivity of the postjunctional membrane, ACh potentials were elicited and recorded. To determine the quantum release of ACh from the motor nerve terminal and its rundown, endplate potentials (EPPs) were elicited at 2Hz and recorded. ACh sensitivity was increased with EDR and NST in a dose dependent manner. The extent of increased ACh sensitivity with EDR 10(-6)M was almost equal to that with NST 10(-7)M. In this experiment, these concentrations were used to compare the antagonistic effect of EDR and NST on the effect of dTc 10(-6)M. The depressed ACh sensitivity with dTc was reversed with EDR and NST. The extent of restoration with NST was about three times that with EDR. The quantum release of ACh was increased and rundown was depressed with EDR, but NST had no effect. After pretreatment with dTc, neither EDR nor NST increased the decreased quantum release of ACh nor reversed the enhanced rundown induced by dTc. But under the same condition, both EDR and NST reversed the ACh sensitivity depressed with dTc. These results demonstrate that neither EDR nor NST were able to affect the decreased quantum release of ACh nor the enhanced rundown induced by dTc. The results also suggest that the reversal of fade of twitch tension with EDR and NST does not always result from recovery of rundown of EPP amplitude. PMID- 8433490 TI - [The effect of isoflurane or sevoflurane on circulating blood volume--study under spontaneous breathing]. AB - Changes in circulating blood volume during isoflurane or sevoflurane anesthesia under spontaneous breathing were investigated by the dual indicator dilution method in 13 mongrel dogs. The animals were randomly divided into three groups; control (C) group n = 5, isoflurane (I) group n = 5, and sevoflurane (S) group n = 5. Changes in circulating blood volume (ml.kg-1) at 0, 0.5, 1.0 MAC were 87.7 +/- 8.2-->88.7 +/- 5.0-->91.0 +/- 5.9 in the I group and 84.4 +/- 7.0-->91.4 +/- 7.7-->91.4 +/- 10.2 in the S group, respectively. In the S group, circulating blood volume and plasma volume increased significantly, while in the I group the volumes tended merely to increase. Arterial carbon dioxide tension (PaCO2) in the I and S groups increased significantly at 0.5 and 1.0 MAC, but similar changes were also noted (not significantly) in the C group. Mean arterial pressure, mean pulmonary arterial pressure, and pulmonary capillary wedge pressure tended to increase at 0.5 and 1.0 MAC in the C and I groups, but tended to decrease in the S group. The results suggest that the increase in vascular compliance with sevoflurane under spontaneous breathing has resulted in the increase in plasma volume and circulating blood volume. PMID- 8433491 TI - [Comparison of sevoflurane and halothane in pediatric anesthesia]. AB - In the present study we compared sevoflurane (group S) and halothane (group F) as used in pediatric endotracheal anesthesia. The subjects consisted of 100 pediatric patients, each 50 in group S and F, most of whom underwent otorhinolaryngological surgery. Anesthesia was induced with nitrous oxide-oxygen sevoflurane (GOS) (S 3-5%) or nitrous oxide-oxygen-halothane (GOF) (F 1.5-2.5%), and maintained with GOS (S 2-3%) or GOF (F 1.0-1.5%). In comparing the groups with respect to anesthetic induction, group S required 2.1 min for the loss of consciousness, 6.1 min for ocular fixation and 9.7 min for completion of intubation, while in group F the time intervals for the above items were 2.4, 4.9 and 10.2 min, respectively. No significant differences were found between the two groups except in the loss of consciousness and ocular fixation. Comparison of the groups during maintenance of anesthesia revealed no significant differences, although pulse rate and diastolic blood pressure increased in both groups. When the groups were compared for awakening from anesthesia, group S required 10.1 min for awakening and 11.9 min for extubation, while in group F the time was 13.0 min and 15.4 min, respectively. These values were significantly different. The present study demonstrated that sevoflurane anesthesia is rapid in both induction and awakening as compared with halothane anesthesia, and that GOS inhalation anesthesia with single use of sevoflurane can be usefully applied to pediatric endotracheal anesthesia. PMID- 8433492 TI - [The changes of intraocular pressure during sevoflurane anesthesia in children]. AB - We investigated the intraocular pressure (IOP) during sevoflurane anesthesia in 20 children. We measured IOP, mean blood pressure and heart rate at 7 points in each subject. IOP was measured first after induction, then after vecuronium administration, immediately after intubation, and 5, 10, 15, 30 min after intubation. There were no significant changes in IOP and hemodynamics during sevoflurane anesthesia. We consider that the optimal time for IOP measurement is 5 or 10 min after intubation and the normal range of IOP is within the mean +/- 2 standard deviation. The peak values of IOP were 19.2 and 18.8 mmHg at 5 and 10 min after intubation. The results suggest that normal range of IOP is below 20 mmHg during sevoflurane anesthesia in children. PMID- 8433493 TI - [Effect of combined spinal and epidural anesthesia on blood loss during total hip replacement]. AB - Ninety total hip replacements (THRs) performed by one surgeon were reviewed to compare the effects of different anesthetic techniques on the perioperative bleeding. Half of the THRs were performed under either combined spinal and epidural (CSE) anesthesia with lidocaine or general anesthesia with N2O/O2, vecuronium, enflurane or isoflurane. Deliberate hypotensive technique was not employed in any THR. All patients were female and had suffered from osteoarthritis of the hip joints. The patients in the two anesthesia groups were similar as to age, body weight, height, perioperative hemoglobin level, duration of anesthesia and operation, and blood transfusion requirement. A positive linear correlation existed between total operative blood loss and operation time in each group (P < 0.01). The rate of operative blood loss was significantly higher in the CSE anesthesia (6.2 +/- 3.0 ml.min-1) than in the general anesthesia (5.1 +/- 2.0 ml.min-1), while the amount of blood loss itself was without statistical difference. A significant increase in total volume of perioperative blood loss was also observed in the group with CSE anesthesia (1520 +/- 90 ml) compared with the general anesthesia group (1279 +/- 58 ml). These results show that spinal and/or epidural anesthesia can not always lead to reductions in operative blood loss during THR. PMID- 8433494 TI - [Relation between fingertip temperature pattern and epidural puncture site during epidural anesthesia combined with general anesthesia]. AB - We are employing fingertip temperature monitoring to estimate the spread of epidural anesthesia in patients who received combined epidural and general anesthesia. In this study we examined the relation between fingertip temperature pattern and epidural puncture site. One hundred patients scheduled for elective digestive tract surgery were studied. They were divided into three groups according to the epidural puncture sites as follow; Group 1, T7-9 (n = 26); group 2, T9-12 (n = 48); and group 3, T12-L5 (n = 26). Fingertip temperature was determined by Anritsu thermocouples. These probes were attached to the thumb and the big toe (hand and foot fingertip). The changes of these temperatures were classified to four types. In type 1, the hand fingertip temperatures were elevated after administration of the local anesthetics. In type 2, both hand and foot fingertip temperatures were elevated. In type 3, the foot fingertip temperature was elevated. In type 4, the hand and foot fingertip temperatures were unchanged. In group 1, we found 10 cases of type 1, 13 cases of type 2 and 3 cases of type 3. In group 2; 15, 22, 11 cases respectively. In group 3; 1, 16 cases respectively and 1 case in type 4. In group 1 and 2, the type 1 temperature pattern was observed more than in group 3 (P < 0.01). And in group 3, the type 3 temperature pattern was observed more than in group 1 and 2 (P < 0.01). We found no intergroup difference in type 2 pattern. But there were some exceptions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433495 TI - [Hemodynamic and endocrine responses to prostaglandin E1 induced hypotension during enflurane anesthesia in surgical patients--evaluation by transesophageal echocardiography]. AB - This study was undertaken to find a relationship between cardiac function indices and endocrine functions during prostaglandin E1 induced hypotension in surgical patients. Thirteen patients who underwent either orthopedic or gynecologic surgery were the subjects of the study. Systolic blood pressure decreased to 80 torr with prostaglandin E1 infusion (0.5-2 micrograms.kg-1 x min-1) under enflurane-N2O anesthesia. The cardiac function were judged by transesophageal echo-cardiography. Plasma ANP and ADH levels were measured by radioimmunoassay. Significant reductions in the left atrial diameter and A/R and significant increases in cardiac output were observed, but there were no significant changes in fractional shortening and pulmonary vein flow. Plasma ANP concentrations decreased significantly from 45.3 +/- 5.1 pg.ml-1 (mean +/- SE) of pre hypotension to 32.6 +/- 2.2 pg.ml-1 of control, but plasma ADH levels increased significantly during hypotension (P < 0.05). We could not find any significant correlation between the cardiac function indices and plasma hormone levels. Transesophageal echocardiography is an excellent monitor during induced hypotension. It is difficult to predict the ANP and ADH levels by measuring cardiac function as judged by TEE. PMID- 8433496 TI - [The influence of normovolemic hemodilution on myocardial blood flow]. AB - Normovolemic hemodilution was carried out in adult mongrel dogs by using SALIN HES, and myocardial blood flow was measured by hydrogen clearance method. Moreover, distribution of the blood flow against cardiac output was calculated. The hematocrit levels before hemodilution was 40%. The hematocrit level by hemodilution (at 4 stages) were 26% at S1, 19% at S2, 9% at S3 and 5% at S4. Total of 4 localized myocardial blood flows in the outer and inner layer areas in both left and right cardiac ventricles were measured. All myocardial blood flows from S1 to S4 were significantly elevated by hemodilution and particularly the maximum level was observed at S3. The increase of the myocardial blood flow by hemodilution was larger in the left ventricle area than that in the right ventricle area. The distribution of the blood flow against cardiac output in the left ventricle area was elevated at S1 and S2, while no significant change was observed at S3 and S4. No significant change in the right ventricle area was observed from S1 to S4. The higher the degree of hemodilution, the higher was the decrease of blood flow ratio of the inner layer area/outer layer area in the left ventricle, but no change was observed in the right ventricle area. PMID- 8433497 TI - [Effects of intravenous infusion of isosorbide dinitrate on hemodynamics during anesthesia and surgery]. AB - Ninety nine patients with ischemic changes of the heart on preoperative and intraoperative ECG tracings were studied to evaluate effects of intravenous infusion of isosorbide dinitrate on hemodynamics during anesthesia and surgery. These patients ranging in ages from 24 to 80 years were administered intravenous isosorbide dinitrate at a rate of either 0.5 or 1 microgram.kg-1 x min-1 during anesthesia and surgery. Arterial blood pressure was not influenced with intravenous isosorbide dinitrate at the speed of 0.5 microgram.kg-1 x min-1 during anesthesia and surgery. The arterial pressure of the patients decreased slightly but significantly 30 min after the start of 1 microgram.kg-1 x min-1 of isosorbide dinitrate infusion, but it recovered to the control level at the end of administration of isosorbide dinitrate. Heart rate was unchanged with intravenous isosorbide dinitrate during anesthesia and surgery in both groups, except a mild increase at the end of isosorbide dinitrate infusion of 1 microgram.kg-1 x min-1. Arterial blood oxygen tension showed no decrease during the administration of isosorbide dinitrate and no adverse reactions associated with administration of the drug was detected in this study. Significant improvement of ischemic changes on ECG tracings were observed in about 25% of the patients who received 1 micrograms.kg-1 x min-1 of intravenous isosorbide dinitrate. PMID- 8433498 TI - [Adequate hepatic circulation during induced hypotension]. AB - The effects of prostaglandin E1 (PGE1) on the hepatic circulation was investigated in an extreme situation during acute hemorrhagic hypotension. Eighteen mongrel dogs were divided into two groups of those who received intravenous injection of PGE1 (PGE1 group, n = 9) and those who received control solution (non-PGE1 group n = 9). After anesthetizing dogs with 50% nitrous oxide in oxygen and 0.5% halothane, surgical procedure was carried out. Mean arterial pressure decreased to 50 mmHg by acute exsanguination, and this pressure was maintained by either saline (2.4 ml.kg-1 x h-1) or PGE1 (0.2 microgram.kg-1 x min 1) infused continuously for 2 hours. In dogs, PGE1 maintained the total hepatic blood flow with increased cardiac index and decreased splanchnic vascular resistance, in spite of the decreased mean arterial blood pressure during hemorrhagic hypotension. The result suggests that, in a hypotensive condition PGE1 may be useful in maintaining adequate hepatic circulation. PMID- 8433499 TI - [Volatile anesthetics suppress cardiac function in man; an investigation based on systolic time intervals]. AB - Hemodynamic changes and left ventricular performance were investigated by simplified mechanocardiography using finger plethysmography instead of carotid artery pulse tracing in patients who received 4 volatile anesthetics with or without nitrous oxide. Systolic blood pressure (Ps), diastolic blood pressure (Pd), heart rate (HR), pre-ejection period (PEP), left ventricular ejection time (LVET), isovolemic contraction time (ICP), PEP/LVET, Pd/ICT, and 1/PEP2 were selected as indices which represent hemodynamics and systolic time intervals. Enflurane 0.6 and 1.2MAC prolonged PEP, and shortened 1/PEP2 and Pd/ICT significantly. Addition of nitrous oxide caused more depression. Halothane 0.6MAC prolonged PEP, and shortened 1/PEP2 and Pd/ICT. Sevoflurane 1.2MAC shortened only 1/PEP2. Addition of nitrous oxide prolonged PEP and PEP/LVET, and shortened Pd/ICT. Isoflurane 1.2MAC lowered Ps and increased HR. The results indicate that cardiac performance was depressed by volatile anesthetics in the order of enflurane, halothane, sevoflurane and isoflurane. PMID- 8433500 TI - [Hemodynamic changes during pneumonectomy especially changes of right ventricular ejection fraction]. AB - Hemodynamic changes were studied in 14 patients during pneumonectomy using a rapid computerized thermodilution catheter, which is capable of measuring right ventricular ejection fraction (RVEF). Measurements were also performed during perioperative period. Ten minutes after clamping pulmonary artery, RVEF, pulmonary artery resistance index (PVRI) and stroke volume index (SVI) showed an increased right ventricular afterload. The RVEF is a useful and fast responding monitor of right ventricular afterload. It has been suggested that the PVRI may be a reliable safety index to decide the indication of pneumonectomy. We conclude that the right ventricular ejection fraction measured by a rapid computerized thermodilution catheter, can be helpful in hemodynamic monitoring during perioperative period of pneumonectomy. PMID- 8433501 TI - [An application of a linear statistical model in clinical anesthesia practice]. AB - One of the important topics in clinical practice of anesthesia, is "prediction". We have to predict what will happen next after obtaining some imperfect data about the patient. The standard and most popularized method is the one utilizing a linear statistical model. This linear model in prediction is based, in part, on the information theory, which says that the volume of information is the linear combination of its components. One of the characteristic models is linear regression analysis. In this paper, basic structure of linear statistical model and its application are discussed. In particular, problems and pitfalls in its application are demonstrated, focusing on variable selection, multi-colinearity and model checking, which will, I believe, lead us to have an access to this clinically important subject "prediction". PMID- 8433502 TI - [Morphological aspects on disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, and hemolytic-uremic syndrome]. PMID- 8433503 TI - [Red cell fragmentation and hemolysis in thrombotic thrombocytopenic purpura (TTP)]. AB - Thrombotic thrombocytopenic purpura (TTP) is an uncommon, life-threatening disorder associated with multiple causes and occurring mainly in adults with multiorgan microvascular thrombosis. The high mortality of this disease needs rapid diagnosis and immediate therapy including plasmapheresis, plasma infusions, corticosteroids and immunosuppressive therapy, which have been improved survival rates of this disorder. Red cell fragmentation due to microangiopathic hemolytic anemia (MAHA) is one of the most characteristic findings in TTP. Identification of red cell fragments and hemolysis is, therefore, important for its rapid diagnosis. It is thought that hemolytic anemia is a consequence of mechanical damage to erythrocytes by fibrin strands, as they traverse peripheral microvessels. However, little is known of the mechanisms of red cell fragmentation and its relation to pathogenesis of TTP. We reviewed red cell deformity and its association to hemolysis by the points of physiologic, chemical and clinical aspects of erythrocytes. PMID- 8433504 TI - [Platelets-morphology, shape changing factor, and platelet agglutinating factor. TTP Research Group]. AB - The morphology of circulating platelets in thrombotic thrombocytopenic purpura (TTP) was studied, and basic mechanism of the characteristic shape abnormality found in TTP was investigated in in vitro condition. The platelet shape was spineless sphere (spherical platelets without pseudopods), and shape change persisted 2 months after remission. This type of platelets were produced by long term of activation of normal resting platelets by several agonists except ADP, and induced by dysfunction of both microtubules and microfilaments. These suggest that the shape change in TTP is not specific, but a good parameter for the activity of TTP. PAF activity by the method of Kelton et al. (1984) was detected in only 1 out of 30 samples from 10 patients. PSCF activity was found in 9 out of 29 samples from 10 patients independently from disease activity. Both activities does not reflect the activity of TTP. PMID- 8433505 TI - [Changes in molecular markers in patients with thrombotic thrombocytopenic purpura]. AB - Hemostatic studies found in the patients with Thrombotic thrombocytopenic purpura were discussed. Most of them showed normal routine hemostatic studies; normal prothrombin time, activated partial thromboplastin time, plasma level of fibrinogen. Fibrin degradation products are more consistently abnormal, with approximately to 70% having slight elevations, but less than 25% of titers are greater than 25 micrograms/ml. Although some cases concerning of complication of disseminated intravascular coagulation in the patient with TTP are found in the literature, laboratory and clinical finding suggest that TTP and DIC are separate entities. PMID- 8433506 TI - [Vascular endothelial cell injury as the initial event in thrombotic thrombocytopenic purpura]. AB - It is an important argument whether vascular endothelial injury is the initial event or not in TTP. There is many possible triggers to vascular endothelial injury: Endotoxins, immune complex, and drugs et al. In these conditions, some cytokines (TNF, IL-1 etc.) induce the activation of endothelial cell. Then, neutrophil can adhere to endothelial cells through adhesion molecules. Endothelial cells were injured, by the activation and the adhesion of neutrophil. The injury of the endothelial cells causes the exposure of subendothelial tissues, and then induce the platelet adhesion on these surface for the initial event of platelet aggregates. Although heterogenous triggers and pathophisiological events are recognized in TTP, endothelial cell injury is the initial event or the essential event. PMID- 8433507 TI - [Prostacyclin stability in thrombotic thrombocytopenic purpura. Japan Working Group on TTP]. AB - We investigated changes in prostacyclin stabilization activity of the plasma of 13 patients with TTP, by measurement of PGI2 inhibitory activity attenuation on normal platelet aggregation, induced by ADP (4 x 10(-5)M). PGI2 stabilizing activity of plasma was expressed as the half life (half time) in the time course of attenuation of the inhibitory effect of PGI2 on platelet aggregation. The half time was 16.7 +/- 5.8 min in the plasma of 10 healthy subjects. The half time in 10 plasma samples from patients in the acute state of TTP was significantly (p < 0.05) shorter than that of normal plasma. The half time become longer in 8 plasma samples after plasma exchange and increased to normal plasma level, in remission. There was no relationship between the concentration of plasma lipoprotein A1 and the half time of PGI2 stabization activity of plasma. PMID- 8433508 TI - [Multimeric composition of von Willebrand factor in thrombotic thrombocytopenic purpura. Japanese TTP Study Group]. AB - Thrombotic thrombocytopenic purpura (TTP) is an uncommon disorder. Several hypotheses have been reported up to now but, the pathogenesis is not yet clear. On the other hand, von Willebrand factor (vWf) plays a role in platelet agglutination in initial hemostasis. Moake and other investigators suggested plasma vWf abnormalities. In this paper, we analysed vWf antigen, ristocetin cofactor (RCof) and multimeric composition of vWf in 16 patients with TTP. It was found that vWf antigen and RCof ranged from very low to very high levels, but RCof was lower than vWf antigen except in two cases. Decrease of large multimer of vWf was seen in 11 patients (69%). These abnormalities were corrected at remission by therapy. PMID- 8433509 TI - [Disseminated intravascular coagulation--pathophysiology]. AB - The main cause of DIC (disseminated intravascular syndrome) is contact of tissue factor with circulating blood. The main symptoms of DIC are bleeding diathesis caused by consumption coagulopathy and organ dysfunction related to circulatory disturbances due to multiple thrombi. However, the symptoms of DIC differ according to degree of fibrinolysis which is characterized by causal disease of DIC. Usually, enhanced fibrinolysis does not cause organ failure but hemorrhagic diathesis, while impaired fibrinolysis does not cause severe bleeding but organ dysfunction. In almost all cases of acute leukemia and in some cases of solid cancer with DIC, hyperfibrinolysis is common. In cases of severe infection with DIC, impaired fibrinolysis due to abnormal elevation of plasminogen activator inhibitor-1 is frequently seen. PMID- 8433510 TI - [Immunological studies of thrombotic thrombocytopenic purpura]. AB - We studied the immunological changes in eight cases of thrombotic thrombocytopenic purpura (TTP). At autopsy, one case showed IgM deposition in the walls of the capillaries of heart and spleen. Coombs' test was negative in all cases and rheumatic factor was positive in four of eight cases. Anti-nuclear factor was positive in three cases including one case showed positive only during remission. One case, who was diagnosed as TTP complicated with systemic lupus erythematosus (SLE) showed some serological abnormalities for LE test, anti streptkinase, anti-DNA antibodies, platelet bound IgG, and serum level of IgG by renal biopsy. There were little changes in complements levels. Platelet associated IgG (PAIgG) was positive in four of six cases, and this seemed to be the only abnormality associated with remission and relapses of TTP. PMID- 8433511 TI - [Histopathology of thrombotic thrombocytopenic purpura]. AB - The most striking lesions of thrombotic thrombocytopenic purpura (TTP) are the subendothelial hyaline deposits and multiple occlusive thrombi. They are found in the small arteries, arterioles, and capillaries of many organs, especially the heart, brain, kidneys, and adrenal glands. Immunohistochemical examination demonstrates that the thrombi in TTP are strongly positive for von Willebrand factor (vWF) antigen, but only weakly for fibrinogen/fibrin. Electronmicroscopically, the thrombi in TTP were composed of tightly packed platelets, showing varying degrees of cytoplasmic alteration and degranulation with a small amount of interspersed fibrin and amorphous materials. Many etiological factors causing intravascular platelet aggregation have been postulated, including unusually large vWF multimers, platelet agglutinating proteins and immune abnormalities. All the lesions in TTP are strongly positive for vWF antigen. This result suggests that vWF multimers may play an important role in the pathogenesis of TTP. PMID- 8433512 TI - [Clinical manifestations and laboratory findings of thrombotic thrombocytopenic purpura]. AB - Clinical manifestations and laboratory findings in 40 patients with thrombotic thrombocytopenic purpura (TTP) in Japan are reviewed. The most common clinical features were central neurological sings. jaundice, fever, hemorrhagic tendency, and renal abnormalities. Laboratory tests showed anemia, thrombocytopenia, hyperbilirubinemia, high serum LDH levels, and low serum haptoglobin levels. BUN and serum creatinine levels were elevated only in about 15% of the patients, although microscopic hematuria and proteinuria were observed more frequently (about 70%). Autoantibodies, such as antinuclear antibody and rheumatoid factor, were also observed in 4% to 9% of the patients. Coagulation and fibrinolysis studies showed normal values in the majority of the patients, suggesting intravascular generation of thrombin and plasmin was minimal in TTP. PMID- 8433513 TI - [Three cases of chronic relapsing thrombotic thrombocytopenic purpura]. AB - We experienced three cases of thrombotic thrombocytopenic purpura (TTP) with repeated relapse and remission, in which the relapse was improved by plasma infusion. One case has continued remission after one relapse. The second case went into remission after several relapses, which were induced by viral infection and pregnancy. The third case has shown repeated chronic relapses over 7 years without any inducing factors. The course of TTP relapse commenced with thrombocytopenia accompanied by microangiopathic hemolytic anemia and neurological disturbances developed over 1-4 weeks. The volume plasma needed for recovery gradually increased with time from the start of relapse. These relapses were unable to be prevented by oral administration of antiplatelet agents (aspirin and dipyridamole). PMID- 8433514 TI - [Upshaw-Schulman syndrome]. AB - Upshaw-Schulman syndrome is a rare congenital disease, with thrombocytopenia and microangiopathic hemolytic anemia, which can be temporarily and repeatedly corrected by the transfusions of plasma from normal donors. Although the pathogenesis of this congenital disorder remains unknown, it appears that patients with this syndrome lack an unidentified plasma factor, which is normally present in plasma and is genetically determined. PMID- 8433515 TI - [Treatment of thrombotic thrombocytopenic purpura--retrospective analysis on Japanese patients and review. Japan TTP Research Group]. AB - Thrombotic thrombocytopenic purpura (TTP), uncommon and still unclarified in pathogenesis, has been treated by various methods, including antiplatelet drugs, steroids, heparin and recently, plasma infusion, and plasma exchange. To evaluate the effectiveness of each therapy or its combination, we analyzed the data of 56 patients with TTP in Japan by a questionnaire. The mortality was 26.8%. Plasma exchange and infusion usually combined with other drugs (steroids, antiplatelet drugs etc.) seemed more effective than therapies without exchange or infusion. We employed a scoring method to express the severity of TTP, using platelet count, hemoglobin level and serum lactate dehydrogenase, creatinine and bilirubin levels as parameters. This scoring method showed objectively the effectiveness of antiplatelet drugs, steroids, or plasma exchange or infusion, and especially, the effectiveness of the latter two (singly or combined) in seven patients who did not respond to other therapies. In conclusion, plasma exchange and infusion are suggested for the treatment of TTP, especially, the severe type. Combination of antiplatelet drugs and/or steroids remains to be evaluated. PMID- 8433516 TI - [Changes and progress in the treatment of TTP--protocols of therapeutic plasma infusion and plasma exchange--therapeutic results by the Japanese and Canadian Study Groups]. AB - Plasma exchange (PE) and plasma infusion (PI) are effective in the treatment of TTP (thrombotic thrombocytopenic purpura). Comparison of PE and PI in the treatment of TTP was carried out by the Canadian Apheresis Study Group, which reported that PE was superior to PI. The Japanese TTP Study Group made a therapeutic protocol in which a smaller volume of Fresh frozen plasma (FFP) was used in the treatment with PI. The efficacy of PE and PI was similar. The results suggest that the volume of FFP necessary for effective treatment is not very large. PMID- 8433517 TI - [Hemolytic uremic syndrome (HUS): pathophysiology--with reference to the differentiation between HUS and thrombotic thrombocytopenic purpura]. AB - HUS and TTP have the same fundamental pathologic lesion, thrombotic microangiopathy, induced by many possible causes, all of which initially induce endothelial cell damage. This damage triggers a cascade of biochemical events that ultimately leads to the formation of thrombi in the microcirculation. HUS and TTP share hematologic and vascular abnormalities and are sometimes similar in their clinical manifestations, some authors believe they should be considered a single condition and be termed HUS/TTP. On the contrary, others consider that HUS could be defined as a disorder marked by microvascular lesions limited to the kidney, whereas TTP has generalized lesions. The causative factor(s) resulting in either HUS or TTP have not been completely elucidated, and further studies are required for precise differentiation between HUS and TTP. PMID- 8433518 TI - [Hemolytic-uremic syndrome]. AB - Hemolytic uremic syndrome (HUS) occurs most commonly in sporadic or epidemic form in otherwise healthy infants or children. The most common agent is Escherichia coli-producing verotoxin (VTEC) in classical HUS. In this paper, the cause or pathogenesis of HUS associated with verotoxin, Shigellosis, streptococcus pneumoniae was described referring to current literature. In addition, this paper also refers to the relationship of HUS with bone marrow transplantation, cancer and renal transplantation. The conclusions were that two syndromes of HUS and TTP may occupy the opposite ends of a continuum with overlap in some cases; the gestalt of a typical case of HUS is quite different from that of a typical case of TTP. Precise definition must await the development of further information concerning the cause and mechanism that produce the subsets or variant forms of HUS. PMID- 8433519 TI - [Hemolytic uremic syndrome associated with entero-hemorrhagic Escherichia coli]. AB - In 1983, Karmali et al. reported the association between idiopathic HUS with verotoxin producing Escherichia coli (VTEC), and their findings have now been confirmed by numerous other investigators. Recently developed serodiagnosis for VTEC infection is quite useful, and we found that out of 71 patients with HUS, 40 were positive for the antibody against O157 E. coli LPS. 0111 and 026 E. coli were also implicated as etiologic agents in HUS of Japan. PMID- 8433520 TI - [The classification of disseminated intravascular coagulation and the clinical features]. AB - Disseminated intravascular coagulation (DIC) is an acquired disorder, in which activation of the coagulation-fibrinolysis system takes place. DIC has a very varied pathological state that is dependent on several factors, such as, underlying disorders, trigger of DIC and activation of intravascular coagulation. Accurate diagnosis of DIC is therefore needed to confirm the presence of an underlying disorder and clinical manifestations and to investigate blood coagulation and fibrinolytic activities. Rapid diagnosis and adequate therapy produce a successful recovery. In this paper, the variety of DIC is summarized. PMID- 8433521 TI - [Diagnosis and clinical features of hemolytic uremic syndrome]. AB - The hemolytic-uremic syndrome (HUS) is an acute disorder, characterized by the triad of microangiopathic hemolytic anemia, nephropathy and thrombocytopenia. The great majority of patients are children, usually under 4 years of age, although adults can be affected. The onset is abrupt and usually follows gastroenteritis or upper respiratory infection. Later, clinical manifestations based on the triad, such as pallor, jaundice, edema, hypertension and purpura soon develop. The urinary output is reduced and the urine may appear dark yellow or tea colored. Laboratory tests of peripheral blood show severe hemolytic anemia associated with fragmented red blood cells and thrombocytopenia, usually below 50,000/microliters. The blood urea nitrogen, serum creatinine and lactate dehydrogenase concentrations are elevated. Proteinuria and microscopic hematuria, which are indicative of active glomerular damage are also seen. Profound understanding of these manifestations is sufficient to permit an early diagnosis of HUS. PMID- 8433522 TI - [Genetic conversion of neurotransmitter phenotype in transgenic mice]. AB - The mammalian central and sympathetic nervous systems contain three kinds of catecholaminergic neuron (dopamine, norepinephrine and epinephrine neurons). Adrenal medulla also consists of cells producing either norepinephrine or epinephrine as hormones. To switch of catecholamine phenotype in the nervous and endocrine systems, we generated a line of transgenic mice carrying a chimeric gene containing human phenylethanolamine N-methyltransferase (PNMT) cDNA fused to the 4-kb fragment of the human dopamine beta-hydroxylase (DBH) gene promoter. Analysis of transgenic mice indicated that the additional expression of human PNMT in norepinephrine-producing cells can convert these cells to the epinephrine phenotype, and suggested that norepinephrine-producing cells normally possess the fundamental machinery required for the synthesis of epinephrine except for the PNMT expression. PMID- 8433523 TI - [Thromboxane A2 receptor; structure, function and tissue distribution]. AB - Thromboxane A2 is an unstable, yet quite potent metabolite of arachidonic acid. Analysis of cDNAs of human and mouse thromboxane A2 receptors revealed important information in regard to the function of thromboxane A2 and its regulation. Examination of amino acid sequences of the receptors provides some information how the ligand binds to the receptor and how desensitization of the receptor occurs. mRNA of the thromboxane A2 receptor is abundantly expressed in the thymus, lung and spleen, and suggests novel function of thromboxane A2. Further progress on understanding of thromboxane A2 and development of effective drugs may be made on the basis of these findings. PMID- 8433524 TI - [Multiple organ failure related to disseminated intravascular coagulation]. AB - This paper describes the main pathophysiological events leading to multiple organ failure (MOF) related to disseminated intravascular coagulation (DIC), caused by circulatory failure or infection. The main mechanisms responsible for the development of MOF in DIC are discussed, as are both the organ ischemia due to stasis and/or obstruction and the close interrelated reactions between inflammatory reaction, immune system and coagulation systems, especially focused on the close connection between the endothelium and superimposed mediators. PMID- 8433525 TI - [Pathology of disseminated intravascular coagulation]. AB - We reviewed the histopathologic characteristics of DIC in autopsy cases. Typical hyaline microthrombi preferentially occurred in renal glomeruli, pulmonary microvasculature, splenic sinuses, adrenocortical capillaries and others, occasionally associated with degenerative or necrotic changes of parenchymal cells of respective organs partly due to ischemic effects of microthrombi and thromboemboli. Investigating the pathogenesis of microthrombi in hepatic sinusoids of rats intravenously injected with LPS (5 mg/kg B.W.) using double immunohistochemical reactions for LPS and fibrinogen, and electron microscopic observations, fibrin thrombi were largely formed around small necrotic foci of hepatocytes 1 hr after injection, which occurred in the very close vicinity to Kupffer cells phagocytizing LPS, and on the cytoplasmic surface of swollen Kupffer cells lading LPS 3 hr after injection. Neutrophils always aggregated in the necrotic foci. Thus, activated Kupffer cells by LPS seemed to play a central role in the development of fibrin thrombi in hepatic sinusoids of endotoxemic rats, through the activation of coagulation system probably via the expression of tissue factor by activated Kupffer cells. PMID- 8433526 TI - [New useful parameters or makers in diagnosis and condition. Analysis of disseminated intravascular coagulation--mainly molecular markers]. AB - New assays for thrombin-antithrombin III complex, plasmin-alpha 2-plasmin inhibitor complex, FDP-D-dimer, t-PA/PAI-1 complex and prothrombin fragment F1+2 are reviewed as molecular markers for disseminated intravascular coagulation (DIC). These are sensitive to early stage indication of DIC. Fluctuation of their levels was also relative to the state of DIC. It is therefore believed that they will play an important role in the diagnosis of DIC, as solid members of its parameter. On the other hand, t-PA/PAI-1 complex is suggested to be the complication marker of DIC, such as multiple organ failure (MOF), as its level was thought to reflect endothelial cell stimulation during DIC. PMID- 8433528 TI - [Thrombotic microangiopathy (DIC,TTP and HUS)--recent advances in pathogenesis and management]. PMID- 8433527 TI - [Progress in diagnosis of disseminated intravascular coagulation (DIC)- diagnostic criteria of DIC]. AB - DIC is an acquired disorder in which intravascular coagulation may lead to microvascular fibrin formation and a hemorrhagic diathesis. If DIC is acute and severe, fibrin formation may lead to microvascular thrombosis, and consumption of coagulation factors and platelets may result in a hemorrhagic diathesis. Secondary to or simultaneously with coagulation, the fibrinolytic system may be activated, accentuating the bleeding tendency. All the systems involved in DIC, such as coagulation, fibrinolysis, kallikrein-kinin, complement, and possibly other systems are regulated. Coagulation is the central event of DIC. The different coagulation factor derivatives may be generated that can be determined and used as markers for the degree of DIC and for effective control of therapy. Some of the procoagulant and anticoagulant factors are converted in the course of coagulation to their active forms and activation peptides. The active factor is subsequently neutralized by forming a complex with an inhibitor. Hemostatic molecular markers, D-dimer of cross-linked fibrin degradation products (D-dimer), thrombin-antithrombin III complex (TAT), and plasmin-alpha 2-plasmin inhibitor complex (PIC) have all been used for the diagnosis of DIC. PMID- 8433529 TI - [Recent advances in diagnosis of disseminated intravascular coagulation in obstetrics and gynecology]. AB - Since obstetrical DIC is an acute serious situation, complicated time-consuming tests do not help to make a prompt diagnosis of DIC. Lowered ESR, prolonged bleeding time and defective patterns of thrombelastography are the suggestive findings of DIC, which are available at the bed-side. Obstetrics-specific DIC scoring system, in which high scores were given for clinical items, rather than laboratory tests, showed a good correlation with the regular DIC score in Japan. Since blood samples obtained from pregnant or parturient women showed different patterns of coagulation and fibrinolysis from the nonpregnant condition, attention should be paid to diagnose obstetrical DIC as accurately as possible. PMID- 8433530 TI - [New approach to the diagnosis of disseminated intravascular coagulation in childhood]. AB - The peak incidence of DIC in the pediatric age group is in the neonatal period. The newborn infant is particularly susceptible to DIC because of several handicaps, such as physiological hypofunction of anticoagulant and fibrinolytic systems, an underdeveloped capacity in the reticuloendothelial system and a tendency to develop acidosis, hypothermia, hypoxia and shock. Although some criteria have been reported for the diagnosis of DIC in adults, based on clinical and laboratory findings, these are not necessarily applicable to the diagnosis of DIC in newborn infants. This is because a large blood sample is required, a long period of time is necessary for assay and difference in several coagulation and fibrinolysis factors exist between newborn infants and adults. We therefore established a criteria for the diagnosis of DIC in newborn infants, based on data obtained from newborn infants with DIC. Diagnostic procedures of many molecular markers of hemostasis have been developed from this. Some of them, such as FDP-D dimer are valuable for the diagnosis in children but others are not necessarily useful because of the susceptibility to the venipuncture technique. Our criteria for the diagnosis of DIC in newborn infants must be modified in the diagnosis of DIC in very low birth weight infants. PMID- 8433531 TI - [Diagnosis of predictive state of disseminated intravascular coagulation]. AB - The early stage of the state in which coagulation or fibrinolytic pathway is activated has been difficult to be estimated. Recently, it has become possible to detect an early stage of DIC (pre-DIC) due to the development of highly sensitive methods which quantitate so called "molecular markers". Molecular markers can be classified into three groups: 1) activation fragments of coagulation proteins (e.g. F1+2); 2) protease and its inhibitor complex (e.g. TAT, IXa-AT-III, Xa-AT III and PIC); 3) degradation products (e.g. FPA, FPB beta, SFMC and D-dimer). Among them, F1+2, TAT, FPA and SFMC reflect in vivo thrombin generation, while PIC, FPB beta and D-dimer reflect in vivo plasmin generation. IXa-AT-III and Xa AT-III may be useful markers to detect hypercoagulable states in an earlier stage of underlying various disorders. Measurement of circulating levels of the zymogens and protease inhibitors is unable to detect small changes caused by low grade DIC or localized thrombotic events. Monitoring plasma levels of molecular markers, however, gives us more specific and accurate information regarding the onset and time course of hypercoagulable states and enable us to diagnose DIC at an early stage and to evaluate the effect of treatment for patients with DIC, specifically. PMID- 8433532 TI - [Synthetic protease inhibitors in the treatment of disseminated intravascular coagulation]. AB - Anticoagulant therapy, correction of the hypercoagulable state underlying DIC (disseminated intravascular coagulation), can help the treatment of DIC. Synthetic protease inhibitors, which can block serine proteases, such as thrombin and plasmin, in the coagulative-fibrinolytic system, could prevent activation of coagulation factors and development of DIC, if administered properly. Clinically applicated protease inhibitors at present, such as gabexate mesilate (FOY), nafamostat mesilate (FUTHAN), urinastatin (MIRACLID), do not have the same spectrum of action, but the common characteristics are as follows. These inhibitors may be superior to heparin and do not require antithrombin III for their activities because of the competitive inhibitors to coagulative enzymes. The half time of these agents in human circulating blood is within several minutes and shorter than that of heparin. PMID- 8433534 TI - [Evaluation of lidocaine metabolite (monoethylglycinexylidide) as a liver function test]. AB - In order to determine whether or not the lidocaine metabolism, monoethylglycinexylidide (MEGX) formation, could be used as a liver function test, we measured the serum levels of MEGX in 38 patients. There were significant correlations between values of MEGX (MEGX15, MEGX30, AUC15-30, AUC0-180) and conventional liver function tests (ICG R15, AT III, T. Bil). It appeared that value of MEGX 30 had maximum factor loading on conventional liver function tests by using principal component analysis. The advantage of adapting the MEGX formation as a liver function test of drug metabolism is simplicity of the method. MEGX formation could be useful index of the total liver function. PMID- 8433533 TI - [Antiinflammatory effects of the betamethasone sodium phosphate enema on carrageenan induced colitis in the rabbit]. AB - The effect of the betamethasone sodium phosphate (BSP) enema on the colonic mucosal lesions in the carrageenan induced colitis (rabbit) was examined laboratory and histologically. The effect of drugs were evaluated by the changes of body weight, fecal occult blood, blood analysis, and histological examinations. Fecal occult blood were highly positive in the physiological saline treated but less positive in the BSP groups. In the blood analysis, anemia was not detected in both groups. Histological findings such as the defect of superficial epithelium, crypt abscess, inflammatory cell infiltration, atrophic changes, defect of muscularis mucosae, goblet cell depletion, goblet cell depletion, ulcer formation, and edematous change were scored to evaluate the colonic mucosal lesions. These scores (Mean +/- S.D.) were 4.4 +/- 1.96, 7.7 +/- 3.67 for BSP, physiological saline groups respectively. From these results, BSP enema showed an antiulcerative effect on the entire colonic lesions in the carrageenan induced colitis in the rabbit. PMID- 8433535 TI - [Comparison of hepatic tissue extraction rates of cytotoxic anticancer drugs during hepatic arterial chemotherapy--evaluation using direct hemoperfusion under hepatic venous isolation]. AB - Hepatic extraction rates (ER) of anticancer drugs during hepatic arterial infusion were investigated with the aid of direct hemoperfusion (DHP) under hepatic venous isolation (HVI). Using mongrel dogs (n = 6), adriamycin (ADR), mitomycin C (MMC) and cisplatin (CDDP) were simultaneously administered to the hepatic artery at each dosage of 1 mg/kg in 10 minutes under HVI.DHP. Hepatic venous flow and plasma concentrations of each drug at the carotid artery, the inlet and outlet sides of DHP were periodically determined during HVI.DHP. Based on these data, drug adsorption and removal rates were estimated. In addition, hepatic tissue uptakes of each drug were calculated from the amounts of drug administered and leaked in the hepatic effluent. Subsequently, the percentage of tissue uptake of each drug to the amount of drug administered was determined as ER of each drug. Drug adsorption rates during the first 10 minutes after infusion showed no significant difference among three drugs. Drug removal rate of CDDP tended to be higher than those of other two drugs. ER of CDDP (54.8 +/- 18.3%) were significantly lower (p < 0.01) as compared to ADR (84.4 +/- 16.2%) and MMC (83.1 +/- 15.7%). These results indicate that ER of each drug should be taken into consideration to determine appropriate drug for hepatic arterial chemotherapy. PMID- 8433536 TI - [The evaluation of portal venous invasion of pancreatic cancer by endoscopic ultrasonography]. AB - Thirty-six cases of pancreatic cancer including 27 cases of so-called mucin producing cancer of the pancreas, examined with endoscopic ultrasonography (EUS) and treated with surgery, were reviewed to evaluate the usefulness of EUS in the diagnosis of portal venous (PV) invasion. The detection rate of pancreatic tumors cancer by EUS was 92% in 36 cases. The detection rate of PV invasion by EUS was compared with histological results in each case. Judgement of the correlation between the tumor and the PV wall was possible in 30 cases (83%), and the overall accuracy of EUS in the diagnosis of PV invasion was 73%. It is concluded that EUS is a very useful method for diagnosis of PV invasion in cases of pancreatic cancer. PMID- 8433537 TI - [A case of amebic liver abscess with colonic carcinoma]. PMID- 8433538 TI - [A case of Budd-Chiari syndrome due to diffuse thrombosis of hepatic veins without involvement of inferior vena cava]. PMID- 8433539 TI - [Immunohistochemical examination of gap junctions in human gastric mucosa with gastric disease]. PMID- 8433540 TI - [Effect of prostaglandin E2 on the proliferation of cultured guinea pig gastric mucous cells]. AB - To understand the mechanism by which prostaglandins (PGs) preserve gastric mucosal integrity, we established a primary cultured monolayer of guinea pig gastric mucous cells, and by using this culture system, we studied whether endogenously released PGE2 could influence the proliferation of the mucous cells. By the histochemical and morphological analysis at 24h of the culture periods, the cells were recognized to contain PAS-positive mucous granules with only 3% of them being parietal cells. Although the cells which were simultaneously labeled with [3H] arachidonic acid in 0.5% serum-containing medium synthesized and released radiolabeled PGE2, PGI2 and PGA2, the release of PGE2 was more markedly observed and was partially dependent upon arachidonic acid added to the culture medium. By radioimmunoassay of the culture media, the mucous cells were found to release PGE2 in a time-dependent manner in response to 10% serum. Pretreatment of the cells with 10(-4)M indomethacin not only inhibited PGE2 release but also inhibited increase in cell number. However, the addition of PGE2 dose-dependently restored the indomethacin-induced inhibition of cell growth with the maximal increase almost to the control level at 10(-6)M PGE2. These results suggest that PGE2 endogenously released from the cells may exert a proliferative effect on gastric mucous cells. PMID- 8433541 TI - Dr. Schloesser receives Eliot Award. PMID- 8433542 TI - Prolonged QT interval and 2:1 atrioventricular block. PMID- 8433543 TI - Perinatal transmission of hepatitis B in Kansas. PMID- 8433545 TI - The genie. PMID- 8433544 TI - Limits of APTT for monitoring heparin. PMID- 8433546 TI - Managed competition: answer to the health care dilemma? PMID- 8433547 TI - Is a chiropractor a physician? PMID- 8433548 TI - Polycystic kidney disease: primary extracellular matrix abnormality or defective cellular differentiation? AB - Polycystic kidney disease (PKD) is inherited as a dominant or recessive trait or can be provoked by environmental factors. The disease is characterized by the growth of large epithelial-lined cysts derived from the nephrons and collecting ducts of affected kidneys. Cysts are thought to initiate as small dilations in renal tubules, which then expand into fluid-filled cavities of relatively large size. Cyst formation appears to involve increased cell proliferation, reversal of tubular epithelial polarity, and epithelial fluid secretion. In addition, a number of pronounced extracellular matrix changes have been found in the cystic kidneys of several animal models and in human autosomal dominant PKD. These abnormalities include thickened, laminated basement membrane, increased expression of alpha 1 type IV collagen and laminins B1 and B2, and changes in heparan sulfate proteoglycan and fibronectin. Some of these changes can also be seen in vitro, reflecting intrinsic abnormalities, and may be associated with abnormal tubular morphogenesis early in cyst formation as well as later in cyst expansion. We have been investigating gene expression in the C57BL/6J-cpk mouse, which has an autosomal recessive form of PKD, to determine the genetic basis of the abnormal tubule cell growth and morphology manifested during cyst formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433549 TI - The glomerular mesangium in diabetes mellitus. AB - Like the renal glomerular mesangium in patients with diabetic nephropathy, glomerular mesangial cell cultures grown in 30 mM glucose accumulate increased amounts of the extracellular matrix (ECM) proteins fibronectin, laminin, and type IV collagen. This is due to increased ECM protein synthesis and mRNA levels. Similar to other cells types that are affected by the diabetic state (such as, vascular cells and peripheral nerve), mesangial cells transport glucose by an insulin-independent, facilitated diffusion transport system. Kinetic studies reveal that intracellular glucose levels may reach the ambient glucose concentrations achieved in diabetes. Growth studies reveal that glucose does not exert its effect on mesangial cell ECM accumulation by affecting cell growth, but rather it causes an increase in diacylglycerol (DAG) mass and activates protein kinase C. Agents such as phorbol myristate acetate (PMA) and the cell permeable DAG analogue, oleoyl acetyl glycerol (OAG) which activate protein kinase C also increase ECM mRNAs. These results implicate protein kinase C activation in the increased ECM accumulation observed in mesangial cell cultures grown in high glucose. PMID- 8433550 TI - Renal tubular basement membrane and collagen type IV in diabetes mellitus. AB - The pathogenesis of the multiple structural lesions in diabetic nephropathy remains debated, and likely is multifactorial. The uniform thickening of the renal basement membranes lining the glomerular and tubular elements appears to be a consequence of the metabolic perturbations which are directly related to hyperglycemia. While most investigations have focused on the increased accumulation of extracellular matrix in the glomerular basement membrane and the mesangium, and their relation to derangements in glomerular function, little is known regarding the pathogenesis and the significance of the tubulointerstitial changes and the thickened tubular basement membrane (TBM). It is possible that these latter changes are causally related to the cellular hypertrophy of the renal tubular epithelium that lines the TBM. It has been postulated that in the earlier stages of the disease, hyperglycemia induces renal tubular hypertrophy and stimulates the synthesis of the various matrix components which are normal constituents of the TBM. Later, the structural composition of the TBM is susceptible to further modifications by non-enzymatic glycation, and this aberrant process may impart a relative resistance to matrix degradation leading to a slow turnover. In vitro investigations on murine proximal tubule cells in culture have provided evidence that elevated ambient glucose is a sufficient stimulus for cellular hypertrophy and increased biosynthesis of collagen type IV, the predominant constituent of TBM. High glucose levels increase steady-state collagen IV mRNA, partly due to transcriptional activation of cis-acting elements of the gene which are controlled by putative glucose-responsive trans-acting proteins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433551 TI - Expression of type I collagen mRNA in glomeruli of rats with passive Heymann nephritis. AB - In passive Heymann nephritis (PHN) glomeruli exhibit marked basement membrane expansion around subepithelial immune deposits but they fail to show any change in mRNA levels of type IV collagen, laminin or fibronectin by Northern and slot blot analysis, or in the amount or distribution of type IV collagen or laminin by immunohistology for up to 12 weeks after disease onset. On the other hand, in situ hybridization (ISH) revealed the appearance of positive cells exhibiting mRNA for the alpha 1 chain of rat type I collagen two to three weeks after the onset of PHN in all glomeruli of all rats. Positive cells persisted for at least eight weeks. In many glomeruli, the location of the clusters of silver grains suggested that they were in visceral epithelial cells. In controls injected with normal sheep IgG, and in early PHN (< 11 days after sheep anti-Fx1A), glomeruli were negative but cells in the renal capsule and adventitia of vessels showed strong ISH and served as positive controls. RNAse pre-treatment and the "sense" probe gave appropriately negative results. RNA from PHN glomeruli contained an alpha 1 type I collagen transcript of the same size as that from rat fibroblasts. These results show that the evolution of glomerular basement membrane expansion in rat membranous nephropathy coincides with the induction of a matrix gene that is not normally expressed in glomerular cells. Further, they suggest that the intercalation of ectopically-expressed matrix molecules may contribute to the production of a disorganized basement membrane. PMID- 8433552 TI - Immune modulation of biologic systems in renal somatic cells. AB - The various theories discussed here suggest that somatic renal cells are susceptible to biologic modulation by the immune system independent of an inflammatory effect. (1) The mode of repression of type IV collagen synthesis by novel, soluble antigen-binding proteins, the down-regulation of class II MHC expression with interruption of antigen presentation to epithelia after selective gene regulation by antibody, and the diverse interactions of antibody with renal glomerular cells producing functional disturbances in endocytosis and permselectivity; (2) modification of surface-antigen composition; (3) alteration of matrix deposition, remodeling and composition; (4) biophysical perturbation of cytoskeletal and cell membrane components; (5) and lastly, alterations in cell adhesion through cell-surface alterations, all lend testimony to the richness of the signal transduction pathways in somatic cells. Although the preceding examples represent only a small fraction of those which may take place within the glomerular and tubular microenvironments, these paradigms may nevertheless serve as new models upon which one can consider the multitude of potential communications between disparate biologic systems that connect in complex organisms. PMID- 8433553 TI - Biological functions of entactin. AB - Entactin is a sulfated multidomain glycoprotein component of basement membranes. The molecule consists of 1217 amino acids which are organized into two terminal globular domains linked by a rod-like structure largely composed of four EGF- and one thyroglobulin-like cysteine-rich homology repeats. Entactin binds to laminin, collagen IV, fibrinogen, and fibronectin. In the parietal endoderm M1536-B3 cell line, the laminin-entactin complex is formed intracellularly and transported in membrane enclosed vesicles to the extracellular compartment. Transfection of human choriocarcinoma JAR cells, which do not synthesize entactin, with entactin cDNA results in the synthesis and insertion of entactin into the extracellular matrix where it becomes associated with laminin and collagen IV. Indirect immunofluorescent staining also reveals that entactin co-localizes with fibronectin in the extracellular matrix of the embryonal carcinoma-derived 4CQ cell line. These observations suggest that entactin plays an important role in the assembly and properties of diverse extracellular matrices. In addition, entactin binds to immobilized fibrinogen, and more specifically, to the A alpha and B beta chains. The binding of radiolabeled entactin to immobilized fibrinogen is not dependent on metal ions, and is inhibited by antibodies against either fibrinogen or entactin, soluble fibrinogen, and unlabeled entactin. This interaction combined with the chemotactic and phagocytic promoting activities of entactin may be important in hemostasis and would healing. PMID- 8433554 TI - Role of a basement membrane glycoprotein in anti-tubular basement membrane nephritis. AB - Tubulointerstitial nephritis antigen (TIN antigen) is a basement membrane component which is recognized by human autoantibodies in TIN and has been shown to induce TIN in Brown Norway (BN) rats. Detectable by immunofluorescent microscopy, TIN antigen reacts with monoclonal, polyclonal, and human autoantibodies in basement membranes of kidney cortex, small intestine, skin and cornea. Specific sites of TIN antigen within kidney cortex include basement membranes of proximal tubules, distal tubules, Bowman's capsule and peritubular capillaries, with highest concentration in proximal tubular basement membrane (TBM). TIN antigen is also present in interstitium between tubules and in the periarterial sheath, but not in glomerular basement membrane or mesangial matrix. Immunoblotting of TIN antigen isolated from rabbit TBM reveals a major 58 kDa component with minor components of 300 kDa, 175 kDa, 160 kDa, 100 kDa and 50 kDa. Partial protein sequence analysis indicates that 58 kDa TIN antigen represents a newly defined glycoprotein. The structural relationships between various molecular weight forms are currently being investigated. High molecular weight (HMW) forms of TIN antigen, consisting of a mixture of 300 kDa, 175 kDa and 160 kDa forms, are more efficient than low molecular weight (LMW) forms (58 kDa and 50 kDa forms) in inducing TIN in BN rats. The resultant antibody specificity of rats injected with either HMW TIN antigen or LMW TIN antigen is identical as determined by immunofluorescent microscopy and Western analysis. Higher antibody titers and greater amounts of kidney-bound IgG are found in the HMW TIN antigen immunized animals. TIN antigen is the primary target of anti-TBM antibodies in human and experimental immunologically-mediated anti-TBM nephritis. PMID- 8433555 TI - Human 92 kDa type IV collagenase: functional analysis of fibronectin and carboxyl end domains. AB - Two closely related secreted metalloproteases 72 and 92 kDa type IV collagenases (72- and 92T4Cl) consist of several structural domains, the functions of which are poorly understood. Both metalloproteases can bind to gelatin as well as form complexes with specific inhibitors in the proenzyme form. The biologic role of the proenzyme-inhibitor complex formation remained unclear. Here we summarize results demonstrating that the fibronectin-like domain of 92T4Cl mediates gelatin binding of the proenzyme, while the hemopexin like carboxy-terminal domain is essential for the complex formation of the proenzyme with TIMP. The formation of a 92T4Cl proenzyme complex with TIMP prevents dimerization, formation of the novel complex with ClI proenzyme, and activation of the 92T4Cl by stromelysin. Conversely, formation of the covalent 92T4Cl homodimer excludes the formation of a proenzyme-TIMP complex, thus allowing this form of enzyme to enter into the proteolytic cascade of activation. Both components of the 92T4Cl-ClI complex can be activated in a fashion similar to that of free enzymes, yielding a complex active against both gelatin and fibrillar collagen. PMID- 8433556 TI - Cellular activation of the 72 kDa type IV procollagenase/TIMP-2 complex. AB - Members of the collagenase family of enzymes have been implicated as central mediators of a number of both physiologic and pathologic processes. The 72-kDa type IV collagenase is secreted as a latent proenzyme, complexed with tissue inhibitor of metalloproteinase-2 (TIMP-2). Like other members of the collagenase family, this enzyme complex must be converted to a catalytically active form for proteolytic remodeling of extracellular matrix to occur. In the current study we demonstrate an inducible cell-mediated activation of the 72-kDa type IV procollagenase/TIMP-2 complex. Isolation of the 62 kDa activated enzyme/TIMP-2 complex from conditioned media of concanavalin A treated WI-38 fibroblasts demonstrated that the cell activated species was proteolytically active and amino terminal sequencing gave the sequence YNFF. This is identical to that of the 62 kDa species generated following organomercurial activation of purified 72-kDa type IV procollagenase/TIMP-2 complex. We have also isolated biosynthetically 35S labeled 72-kDa type IV procollagenase/TIMP-2 complex and used this to further study the cellular activation process. In cell lines tested the activator was retained in the residual cell fraction following lysis in the presence of 0.2% (wt/vol) Brij-35. Inhibitor studies demonstrated that processing and activation of 72-kDa type IV procollagenase/TIMP-2 complex by the residual fraction was inhibited by 5 mM ethylenediaminetetraacetic acid and 0.5 mM 1,10-phenanthroline demonstrating a metal atom dependence. The species responsible for activation could be partially recovered in soluble form with 0.5% (vol/vol) Triton X-100 and 0.25% (wt/vol) CHAPS but was not salt extractable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433557 TI - Remembering Homer Smith. PMID- 8433558 TI - Response of genetic hypercalciuric rats to a low calcium diet. AB - A fundamental mechanism for hypercalciuria in genetic hypercalciuric rats appears due to a primary increase in intestinal calcium absorption. However previous studies could not exclude additional mechanisms to account for the hypercalciuria. To determine if enhanced bone mineral dissolution either as a primary abnormality or secondary to a defect in renal tubule calcium reabsorption is responsible for a component of the augmented calcium excretion we studied rats continually inbred for hypercalciuria. Nineteenth generation adult female idiopathic hypercalciuric (IH) and non-inbred control (Ctl) rats were fed 13 g/day of a normal calcium diet (0.6% calcium, NCD) for 10 days. Urine calcium excretion over the last seven days was greater in IH (34 +/- 2 mg/7 day) than in Ctl (2.9 +/- 0.3, P < 0.01) rats. Some rats in each group were continued on the same diet while others were fed a low calcium diet (0.02% calcium, LCD) for an additional 10 days; balance measurements were made over the final seven days. With LCD, urine calcium excretion was approximately 8-fold higher in IH compared to Ctl (13 +/- 2 mg/7 day vs. 1.6 +/- 0.1, IH vs. Ctl, respectively, P < 0.01). In IH rats percent calcium absorption was greater (59 +/- 3% vs. 45 +/- 3, IH vs. Ctl, P < 0.01), however calcium retention was negative (-1.9 +/- 2.0 mg/7 day vs. 6.5 +/- 0.5, IH vs. Ctl, P < 0.01) compared to Ctl rats. The fall in urine calcium excretion when IH rats are fed LCD indicates that enhanced intestinal calcium absorption is a primary mechanism of the hypercalciuria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433559 TI - Laminin variants: why, where and when? AB - Laminin is a member of a family of proteins that are composed of three subunits, one heavy chain and two light chains. Five subunits in the laminin family have been cloned and sequenced so far. These include two heavy chains, the laminin A chain and the merosin M chain, and three light chains, B1, B2, and S. These five subunits can form four different laminin variants: A-B1-B2, A-S-B2, M-B1-B2, and M-S-B2, all having the B2 chain in common. Major basement membranes in tissues contain at least one of the four laminin variants. For example, the adult muscle and nerve basement membranes contain M-B1-B2, smooth muscle contains A-B1-B2, the myotendinous junction and the trophoblast basement membrane in the placenta contain M-S-B2, and blood vessels contain A-B1-B2 and/or A-S-B2. In the brain, the merosin M chain is present in association with neuronal fibers. The four members of the laminin family interact with cells in a similar manner. Thus, they promote outgrowth of neurites from neuronal cells and promote attachment and spreading of non-neuronal cells. The interaction of cells with laminins is mediated largely by integrin type receptors, including integrins alpha 1 beta 1, alpha 2 beta 1, alpha 3 beta 1, and alpha 6 beta 1. The expression of the different laminin-like proteins is developmentally regulated. The laminin A chain is the first heavy chain expressed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433560 TI - Role of laminin in endothelial cell recognition and differentiation. AB - The vascular endothelium normally is maintained in a quiescent state, but under certain conditions it is induced to undergo marked changes in behavior and form new vascular structures. A complex interaction among various growth and differentiation factors and the extracellular milieu regulates this behavior. One series of signals affecting endothelial behavior is provided by laminin, a major structural protein of basement membrane. These signals have been studied using Matrigel, a reconstituted basement membrane preparation from the murine Englebreth-Holm-Swarm sarcoma, in an in vitro assay of endothelial cell differentiation. Three biologically-active sequences from the laminin molecule have been evaluated. Synthetic peptides that include the sequences -RGD-, -YIGSR , and -SIKVAV- mediate, respectively, cell binding to Matrigel, alterations in cell morphology, and induction of migration and collagenase activity. Preliminary data indicate that observations made with this system may be relevant to endothelial function in vivo. Endothelial cell differentiation on Matrigel may thus be a useful in vitro model for the study of certain steps in angiogenesis. PMID- 8433561 TI - Effect of insulin-plus-glucose infusion with or without epinephrine on fasting hyperkalemia. AB - Extrarenal potassium disposal is an important defense against hyperkalemia in patients with end-stage renal disease. Both insulin and epinephrine are important modulators of this process. Hemodialysis patients are prone to developing hyperkalemia during fasting. We tested the hypothesis that the infusion of physiologic doses of insulin prevents fasting hyperkalemia in hemodialysis patients, both by a direct stimulation of extrarenal potassium disposal, as well as by augmenting the potassium-lowering effect of epinephrine. Ten stable, nondiabetic maintenance hemodialysis patients were studied prospectively in a Clinical Research Center. They were fasted for 18 hours, followed by an acute infusion of epinephrine at 0.01 microgram/kg/min, in the absence or presence of prior beta-blockade with propranolol. Serial measurements of plasma potassium, insulin and glucose were obtained. The patients were restudied under the same experimental protocols, while receiving a continuous infusion of insulin with dextrose. The plasma potassium increased by 0.58 +/- 0.13 mmol/liter (P = 0.002) after 18 hours of fasting. Administration of insulin with dextrose at a dose that doubled the plasma insulin levels within the physiologic range (9.3 +/- 1.1 vs. 20.2 +/- 2.3 mU/liter, P < 0.002), completely prevented the rise in plasma potassium (+0.06 +/- 0.13 mmol/liter, P = 0.64). Epinephrine did not significantly change the plasma potassium during fasting alone (+0.05 +/- 0.09 mmol/liter, P = 0.59), whereas it lowered the potassium significantly (-0.16 +/- 0.04 mmol/liter, P = 0.003) when the subjects were receiving insulin with glucose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433562 TI - LDL stimulates mesangial fibronectin production and chemoattractant expression. AB - Hyperlipidemia has been associated with glomerulosclerosis and a glomerular monocyte infiltrate in models of progressive renal insufficiency. The pathogenesis of hyperlipidemia-induced renal injury remains unknown. We postulated that the effect of hyperlipidemia may be mediated through LDL-induced activation of mesangial cells, which have recently been shown to possess LDL receptors. To test this hypothesis, cultured human mesangial cells were co incubated with human LDL. Monolayers treated with LDL demonstrated a greater level of tissue culture supernatant fibronectin than control mesangial cells. This correlated with enhanced expression of fibronectin mRNA in LDL-treated mesangial cells. Additionally, LDL conditioning of mesangial cells caused a dose- and time-dependent increase in the expression of monocyte chemoattractant protein 1 mRNA, a monocyte specific chemotactic factor, as well as an increase in the monocyte chemotactic activity of mesangial supernatants. Thus, the deleterious effects of hyperlipidemia on the kidney may be mediated by the mesangial cell through an increase in production of mesangial matrix and recruitment of inflammatory cells to the glomerulus. PMID- 8433563 TI - Human peritoneal mesothelial cells synthesize interleukin-6: induction by IL-1 beta and TNF alpha. AB - Recent studies have demonstrated increased levels of IL-6 in the peritoneal cavity during CAPD peritonitis. The current investigation was initiated (i) to examine the human peritoneal mesothelial cell (HPMC) as a possible source of this secreted IL-6 and (ii) to characterize the released product and examine its regulation by other cytokines. Unstimulated HPMC under growth arrested conditions released IL-6 in a time dependent manner. After 24-hour HPMC IL-6 release (mean +/- SEM, N = 13) (expressed as pg/micrograms cell protein) was 1.67 +/- 0.33. Stimulation of HPMC with IL-1 beta or TNF alpha resulted in a time (increasing up to 48 hr) and dose dependent IL-6 generation. After 24 hours the levels induced by IL-1 beta and TNF alpha (both at 1000 pg/ml) were (mean +/- SEM, N = 13) 19.08 +/- 2.98 and 6.62 +/- 1.72, respectively. Stimulation with combinations of IL-1 beta and TNF alpha resulted in additive increases in IL-6 release. This release could be inhibited by co-incubation with anti-IL-1 beta and/or anti-TNF alpha antibodies. The level of released HPMC IL-6 measured by immunometric assay (ELISA) correlated directly with that detected in the 7TD1 IL-6 bioassay (r = 0.63; P < 0.001). Western blot analysis of concentrated HPMC supernatants using specific anti-IL-6 antibody demonstrated immunoreactive bands at 23 and 28 Kd following IL-1 beta or TNF alpha treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433564 TI - NMR spectroscopy as a novel approach to the monitoring of renal transplant function. AB - High field 1H NMR spectroscopy was used for the rapid multicomponent analysis of low molecular wt compounds in urine in order to investigate the patterns of metabolic changes associated with early renal allograft dysfunction. Urine samples were collected daily for 14 days from 33 patients who underwent primary renal allograft transplantation, and analyzed by 500 and/or 600 MHz 1H NMR spectroscopy. All patients received 20 mg prednisolone and 5 mg/kg b.d. oral cyclosporin A (CsA) solution. In this study no patient showed clinical or histopathological evidence of CsA nephrotoxicity. For each patient the NMR generated metabolite data were correlated with the clinical observations, graft biopsy pathology, and data from conventional laboratory techniques for assessing renal function. The NMR spectra of urine from patients with immediate functioning grafts were similar with respect to their patterns of amino acids, organic acids and organic amines, whereas the patients with delayed or non-functioning grafts showed significantly different metabolite excretion patterns. In longitudinal studies on individual patients there were increased urinary levels of trimethylamine-N-oxide (TMAO), dimethylamine (DMA), lactate, acetate, succinate, glycine and alanine during episodes of graft dysfunction. However, only the urinary concentration of TMAO was statistically significantly higher (P < 0.025) in the urine collected from patients during episodes of graft dysfunction (410 +/ 102 microM TMAO/mM creatinine) than in patients with good graft function (91 +/- 18 microM TMAO/mM creatinine) or healthy control subjects (100 +/- 50 microM TMAO/mM creatinine). These findings suggest that graft dysfunction is associated with damage to the renal medulla which causes the release of TMAO into the urine from the damaged renal medullary cells. This provides a possible novel urinary marker for post-transplant graft dysfunction. This study shows that NMR spectroscopy of biofluids, when used in combination with conventional laboratory techniques, is a valuable aid to renal transplant monitoring. PMID- 8433565 TI - Growth factors in glomerulonephritis. PMID- 8433566 TI - Adhesion and activation of human neutrophils on basement membrane molecules. AB - In a previous study, we found that type I collagen activates human polymorphonuclear neutrophils by binding to a membrane integrin [3]. The activation depends on two sequences, both contained in the alpha 1 (I) CB6 peptide, one is RGD, starting at residue 915, and the second is DGGRYY, starting at residue 1034 of the alpha 1(I) chain. We checked the effect of several other types of collagens, principally type IV collagen from several origins. The basement membrane from bovine lens as well as type IV collagen prepared from it by tartaric acid extraction did not activate the human neutrophils. In contrast, when neutrophils had been previously in contact with type IV collagen their activation by type I or the alpha 1(I) CB6 peptide, or the bacterial peptide N formyl-methionyl-leucyl-phenylalanine, was inhibited. This effect was abolished when type IV collagen had been previously treated by pepsin. On the other hand, the fractions of type IV collagen that resisted digestion by bacterial collagenase still exhibited this inhibiting effect. This effect probably explains the physiological property of neutrophils to cross vascular walls without being activated. PMID- 8433567 TI - Interaction between the 67 kilodalton metastasis-associated laminin receptor and laminin. AB - Normal and neoplastic cells interact with laminin via a variety of cell surface proteins. The specific binding sites on laminin for each particular cell surface laminin-binding protein have not yet been identified. In this study, the interaction between laminin and the high affinity metastasis-associated 67 kD laminin receptor (67 LR) was investigated by electron microscopy using the rotary shadowing technique. Laminin receptor that was purified from human colon carcinoma metastases appeared as a globular structure with a diameter of 5.2 +/- 0.8 nm. The 67 LR specifically bound to laminin on its long arm close to the intersection of the long and the short arms. There was no specific interaction of bovine serum albumin with laminin. Biochemical confirmation of the rotary shadowing experiments included slot blot solid phase assays in which [I125] labeled 67 LR bound in a dose dependent manner to laminin as well as to the chymotrypsin resistant (C1) fragment of laminin that contains a short piece of the long arm. [I125]-labeled 67 LR did not bind to the pepsin resistant (P1) fragment of laminin that did not contain that segment on the long arm. This study therefore identifies the binding site on laminin for the 67 kD metastasis associated laminin receptor as a region on the long arm of laminin close to the intersection of the four arms. PMID- 8433568 TI - Molecular genetics of Alport syndrome. AB - Alport syndrome is a progressive hereditary kidney disease characterized by hematuria, sensorineural hearing loss and ocular lesions with structural defects in the glomerular basement membrane (GBM). The gene frequency has been estimated to be 1:5000. The disease is primarily X chromosome-linked, but autosomal forms have also been reported. The X-linked form has been shown to be caused by mutations in a recently identified alpha 5(IV) collagen chain gene (COL4A5). We have isolated cDNA clones for providing the entire primary structure of the human alpha 5(IV) chain. The gene has been located to the Xq22 region. Using antibodies against synthetic peptides, the alpha 5(IV) chain was shown to be located in the kidney only in the glomerular basement membrane. Thus far, the exon-intron structure has been determined for a large portion of the gene which probably has a size of over 200 kb. Numerous different mutations have been identified in the COL4A5 gene. The mutations include single base mutations, large deletions and other major rearrangements such as inversion and duplication. The consequences of the mutations observed can be considered sufficient to cause structural and functional defects in the type IV collagen molecule and, therefore, also the GBM network. This, in turn can explain the disruption of the GBM and hematuria occurring in these Alport patients. Alport syndrome is the first genetic basement membrane and kidney disease whose gene has been cloned. These recent results have enabled the development of antibodies and DNA probes for accurate diagnosis of Alport syndrome. PMID- 8433569 TI - Perlecan, the large low-density proteoglycan of basement membranes: structure and variant forms. AB - The complete primary structure of perlecan, the large low-density proteoglycan of basement membranes, has been deduced by cDNA cloning for the mouse and more recently the human gene products. Mouse perlecan contains a 396 kDa core protein with five distinct domains: a heparan sulfate attachment domain, a LDL receptor like domain, two different laminin-like domains and an N-CAM-like domain. These domains are conserved to a striking degree between mouse and human, including alternate splicing of the N-CAM domain to generate variations of perlecan. These variant sequences also appear to be highly conserved between mouse and human. The strong conservation of these domains, including highly repetitive elements and potential alternative splices, suggest they have vital functions. PMID- 8433570 TI - Endothelial integrins and their role in maintaining the integrity of the vessel wall. PMID- 8433571 TI - Role of laminin carbohydrates on cellular interactions. AB - Laminins, a family of large multidomain glycoproteins of the basal lamina, have been implicated in the development and maintenance of cellular and tissue organization. Considerable interest has arisen concerning the ways in which laminin carries out its biological functions. Previously these biologic responses have been primarily attributed to the peptide sequences of laminin, however, newer studies suggest that laminin carbohydrates may also participate in such cellular activities. Recently, a subpopulation of laminin molecules purified from EHS sarcoma by lectin affinity chromatography has been shown to contain about 25 to 30% carbohydrate. Most of the carbohydrates present are complex-type asparagine-linked oligosaccharides encompassing many different structures, some of which are unique to laminin. To date, the biological function of the carbohydrates of laminin remains somewhat unclear. They do not appear to be needed for heparin binding or to enhance proteinase stability, however, current evidence suggests they are important in cellular spreading and neurite outgrowth. It is our hypothesis that in the covalently-linked carbohydrate moieties of laminin will ultimately prove to be involved in information transfer to responsive cells. It is the purpose of this review to delineate current concepts of the structure and function of this unique glycoprotein's sugar chains. PMID- 8433572 TI - Nidogen mediates the formation of ternary complexes of basement membrane components. AB - Using a recombinant nidogen we have probed the calcium binding potential of various nidogen domains, examined the binding of nidogen to various basement membrane proteins and assessed the ability of nidogen to mediate the formation of ternary complexes between laminin and heparan sulfate proteoglycan and collagen IV and laminin. The results of these experiments indicate that the Ca+2 binding is on the rod-like domain with additional binding observed on the N-terminal G1 domain. With regard to the role of nidogen in mediating complex formation among basement membrane components it was demonstrated that nidogen effectively promotes the formation of a ternary complex between laminin and collagen IV, with both of these components interacting independently with nidogen. Similarly, nidogen mediates a ternary complex formation between laminin and proteoglycan. Interestingly, the interaction between proteoglycan and nidogen is through the protein core of the proteoglycan. We have localized the major interaction sites on nidogen with the proteoglycan core and collagen IV to a region on the globular G2 domain while the C-terminal globe G3 binds to laminin. Ca+2 binding does not appear to be important in either of the binary or ternary complex formations. The data reported allow us to hypothesize that, via the multiple interactions of nidogen with other basement membrane components, nidogen plays a crucial structural role in basement membrane organization and stabilization. PMID- 8433573 TI - Laminin distribution in developing glomerular basement membranes. AB - The renal glomerular basement membrane (GMB) separates two distinctly different cell layers: the vascular endothelium, and visceral epithelial podocytes. When initial vascularization of the forming glomerulus takes place during nephrogenesis, the early GBM forms by fusion of a dual basement membrane between endothelial cells and podocytes. As glomerular capillary loops blossom, newly synthesized basement membrane segments derived from podocytes are then inserted or spliced into the fused GBM. The molecular processes accounting for either basement membrane fusion or splicing are unresolved. Using monoclonal anti-mouse laminin antibodies (mAbs) against the end of the laminin long arm (5D3), we have shown in adult mice that peripheral loop GBM is only weakly immunoreactive but the mesangial matrix and tubular basement membrane (TBM) is intensely positive. In contrast, mAbs against domains in the center of the laminin cross only label TBMs and mesangial matrices of mature mice and GBMs are negative. Immunofluorescence microscopy of neonatal mouse kidneys showed, however, that anti-laminin mAbs brightly labeled developing GBMs of glomeruli undergoing initial vascularization and capillary loop formation. Post-fusion GBMs of maturing stage glomeruli became unreactive for most anti-laminin mAbs but remained positive for 5D3. Our results therefore show that some GBM laminin epitopes are transiently expressed during glomerular development. These changes in GBM immunoreactivities may reflect proteolytic processing during basement membrane fusion and splicing, or temporally controlled synthesis of different laminin isoforms. PMID- 8433574 TI - Basement membrane proteoglycans and development. AB - Basement membranes contain distinct collagen, glycoprotein and proteoglycan species, and these exhibit considerable heterogeneity in isoform or type when different tissue types are compared. Additionally, many components are differentially expressed in organogenesis. We have considered the distributions in glomerulogenesis of two distinct basement membrane proteoglycans, a small heparan sulfate proteoglycan and a chondroitin sulfate proteoglycan (BM-CSPG). While the former was present in all kidney basement membranes through development, the latter was apparently regulated in distribution. BM-CSPG was only strongly expressed in the vasculature invading late comma stage glomeruli, and later in presumptive and mature Bowman's capsule. Over the first six to eight weeks, the capillary basement membranes contained BM-CSPG, but in gradually decreasing amounts until it became completely undetectable. The basement membrane of the adult rat glomerulus is unique in its lack of BM-CSPG. However, in diabetic rats, BM-CSPG is apparently re-expressed in the glomerular basement membrane, a potential marker for pathological changes in glomerular structure. While its function awaits elucidation, BM-CSPG may be essential for basement membrane integrity or stability and have important roles in kidney development. PMID- 8433575 TI - Explaining urban-rural differences in the use of skilled nursing facility benefit. AB - Recent closings of rural hospitals, anecdotal evidence of rural elderly persons having difficulty gaining access to health services, and the large and growing number of elderly persons living in rural areas has renewed concern about access to care for the rural elderly. In this study, 1987 Medicare skilled nursing Facility (SNF) bills were used to examine differences in urban and rural use of the SNF benefit. Using multivariate techniques, the analysis found that Medicare enrollees living in rural and large metropolitan areas used the SNF benefit at a rate 20% and 17% higher than enrollees living in small and medium-sized metropolitan areas, respectively. However, in rural areas the swing-bed program plays a major role in assuring access to the SNF benefit. Without the swing-bed program, rural enrollees would use the SNF benefit at a rate comparable to that of enrollees in small and medium-sized metropolitan areas. The importance of the swing-bed program cannot be underscored, because relative to urban enrollees, rural enrollees disproportionately live in nursing home markets that are not amenable to serving Medicare patients. PMID- 8433576 TI - Rural hospital closures. Determinants of conversion to an alternative health care facility. AB - Conversion of closed hospitals to alternative health care facilities is often suggested as a way of maintaining the availability of medical services in rural areas. This study investigates the factors that influence whether or not a closed rural hospital will convert to an alternative health care facility. The study uses primary data collected from a survey of rural hospitals in Texas that closed during the years 1985 through 1990. Regression results indicate that conversion was more likely when the local economy was healthier and when there were fewer substitute forms of health services. Ownership also played a role: government operated hospitals that closed were less likely to convert than were private not for-profit providers. The results of the study will be useful for evaluating programs designed to encourage alternative ways to provide health care services in rural areas. PMID- 8433577 TI - The importance of co-existent disease in the occurrence of postoperative complications and one-year recovery in patients undergoing total hip replacement. Comorbidity and outcomes after hip replacement. AB - Co-existent or comorbid diseases are appreciated as prognostic factors in studies of quality and effectiveness of care when mortality is the end point. The need to measure and adjust for comorbidity in studies of postoperative hospital complications or long-term recovery from surgery has not been documented. In this study, we determined the impact of co-existent disease on post-operative complications and 1-year health-related quality of life in patients hospitalized for a total hip replacement. The study population consisted of a cohort of 356 patients who were hospitalized in four teaching hospitals in California and Massachusetts for a total hip replacement. Patients' medical records were reviewed to collect information regarding severity of illness, co-existent disease, and postoperative complications. The kind and amount of baseline preoperative co-existent disease was measured from medical record information at admission using a four level Index of co-existent Disease (ICED). Approximately 12 months after hospital discharge, 283 (80%) of the patients were surveyed by questionnaire. The presence and amount of co-existent disease were significant predictors of postoperative complications. The complication rates ranged from 3% to 41% between the lowest and highest levels of the ICED. Patients treated at the four study hospitals differed in functional outcomes 1 year after surgery. Functional outcomes were strongly related to ICED scores: patients in Level 4 ICED scored 26.8 points lower in instrumental activities of daily living than patients in Level 1. After controlling for gender, age, education, and marital status, ICED remained a significant predictor of functional status at 1 year. Furthermore, differences among hospitals in functional outcomes disappeared when the ICED was included in the model to adjust for patient characteristics at the time of surgery. A measure of co-existent disease was crucial in explaining differences among hospitals in recovery from total hip replacement patients. PMID- 8433578 TI - Effect of prenatal and infancy nurse home visitation on government spending. AB - A completed series of reports on a randomized trial (N = 400) indicated that, in contrast to comparison services, prenatal and infancy nurse home visitation improved a wide range of maternal and child health outcomes among poor, unmarried, and teenaged women bearing first children in a semirural county in upstate New York. Eighty-nine percent of the sample was white, and all analyses focused on this group. In this article, an analysis of the net cost of the home visitation program from the perspective of government spending is presented. The average per-family cost of the program in 1980 dollars was $3,246 for the sample as a whole, and $3,133 for low-income families. Treatment differences in government expenditures for Aid to Families with Dependent Children, Food Stamps, Medicaid, and Child Protective Services, minus tax revenues due to maternal employment (also expressed in 1980 dollars), were conceived as government savings. By the time the children were 4 years of age, government savings were $1,772 (95% confidence interval [CI]: -$557, $4,102) for the sample as a whole, and $3,498 (95% CI: $569, $6,427) for low-income families. Within 2 years after the program ended, after discounting, the net cost of the program (program costs minus savings) for the sample as a whole was $1,582 per family. For low-income families, the cost of the program was recovered with a dividend of $180 per family. PMID- 8433579 TI - Strategies to increase mammography utilization among community health center visitors. Improving awareness, accessibility, and affordability. PMID- 8433581 TI - Ambulatory testing for capitation and fee-for-service patients in the same practice setting: relationship to outcomes. PMID- 8433580 TI - Factors associated with patient satisfaction among symptomatic HIV-infected persons. PMID- 8433582 TI - The effect of insurance benefit changes on use of child and adolescent outpatient mental health services. AB - Use of outpatient mental health services by dependent children younger than 18 years of age enrolled in the Blue Cross and Blue Shield Federal Employees Plan (FEP) is examined in 1978 and 1983 focusing on a cut in benefits and a shift from high- to low-option plan enrollment between those years. While use rates increased from 2.13% to 2.76% by 1983, the average number of visits decreased from 18.9 to 12.8. High-option plan use exceeded low-option plan use in both years--2.26% versus 0.81% in 1978 and 3.58% versus 1.93% in 1983. In addition to benefit plan, ethnicity, parent's education, type of provider, and type of treatment setting also significantly predicted amount of use. Despite the strong evidence of the effects of benefit coverage, it is likely that need exceeded use even in this insured population of children and adolescents. Implications of the findings are discussed in the context of recent dramatic changes in mental service delivery including privatization, managed care initiatives to cut costs, and growing pressures for national health insurance. PMID- 8433583 TI - [Consumption of drugs in diabetes mellitus II. Utilization and loss of insulin: epidemiologic and socioeconomic implications. Study Group for Diabetes in Tarragona (GEDT)]. AB - BACKGROUND: With the aim of evaluating the real consumption on insulin an analysis of its loss with use in clinical practice was carried out. The influence of this loss was investigated in the calculations of prevalence of diabetes (DM) initiating from the consumption of medication, the presumable repercussion in public health costs and possible alternatives. METHODS: Revision and analysis of the recipients used by a group of 58 insulin treated diabetics was carried out during a mean period of one month. The theoretic consumption, real consumption and the mean loss per each injection according to visual accuracy and the system employed were evaluated. A deduction was made of the autonomy by storing of insulin. A previous calculation concerning the prevalence of DM in Tarragona (548,900 inhabitants) according to consumption was corrected and an economic estimation of the loss demonstrated over public health costs of insulin during 1991 was made. RESULTS: The mean dose prescribed was 39.7 IU/day supplied in 2.4 injections/patient/day. At 30 days (27-35) 310 recipients were evaluated (115 vials/195 boxes). The mean real dose consumed was 53.3 IU/day and the mean loss per injection was 5.6 (25.5% of all the insulin supplied, 4.5% as remnants at the bottom of the recipient). A greater loss was observed by injection a) in patients with reduced sight (6.4 +/- 7.3 IU/5.5 +/- 4.5; NS) and b) in the users of syringes with dead space (5.8 +/- 4.7) with respect to those using an injector insulin pen (4.4 +/- 2.9; p < 0.01). The autonomy by domiciliary storage of insulin was of 103.7 days/patient (prescribed doses) and 78.6 (real consumption). A total of 7 diabetics (12%) had unused expired recipients. The prevalence of insulin treated DM in Tarragona was estimated as around 4.3-4.8/1,000 (2,360 2,635 inhabitants). The expense of loss was 36 million pesetas/year; 6.4 as depreciated remnants of insulin in the bottom of recipients. CONCLUSIONS: There is a great loss of insulin in clinical practice which may be avoidable and which influences the public health costs for diabetes. An adequate educative strategy and system of injection independent of user ability would reduce the costs. PMID- 8433584 TI - [Loss of potential life years through AIDS in Spain 1981-1990]. AB - BACKGROUND: To know the importance of AIDS in premature mortality in Spain in relation to the remaining causes of deaths. METHODS: Deaths of patients with AIDS were obtained from the National AIDS Registry and deaths from other causes from the official mortality statistics. The potential years of life lost (PYLL) were compared from birth until the age of 65 in AIDS patients between 1981-1990 with those observed as the principal causes of premature death in 1980-1988. Similar comparisons were carried out for the three Autonomic Communities with the greatest incidence of AIDS (Catalonia, Madrid and the Basque Country). RESULTS: In 1988, there were 670 deaths (21,987 PYLL) in patients with AIDS and in 1990 this number almost doubled with 1312 (42,543 PYLL). In 1988 the PYLL in AIDS cases were situated at the ninth level for cause of premature death (eight in males) and in 1990 it was estimated to be in the eight place, near lung cancer, hepatic cirrhosis and cerebrovascular disease. In 1988, Madrid which has the highest rate adjusted by age of PYLL in AIDS cases, was placed in sixth place and was expected to reach second place in 1990. CONCLUSIONS: Death by AIDS has rapidly increased while death by the remaining cases has remained much more stable with AIDS nearing the level of the main causes of premature death. The need to consider AIDS as one of the health problems which takes priority is confirmed. PMID- 8433585 TI - [Value of the transcranial Doppler examination in the diagnosis of brain death]. AB - BACKGROUND: Transcranial Doppler examination (TCD) is a non invasive method capable of detecting the interruption of cerebral flow in patients with criteria of brain death. Its recognition as an alternative to isoelectric EEG for the diagnosis of brain death requires previous validation. METHODS: Twenty-six patients in profound coma were examined by TCD. Of 23 patients with technically adequate study 13 manifested clinical criteria and EEG of brain death. Of these patients 9 had received barbiturate treatment and 4 had not. RESULTS: Changes in the flow waves of the TCD were observed in the form of diastolic reflux or systolic points of slight amplitude without diastolic flow in at least 2 arteries in 12 of 13 patients with criteria of brain death (sensitivity = 92%) and in none of the 10 patients without criteria of brain death (specificity = 100%). The use of barbiturates did not modify the normal anterograde flow detected by TCD in the absence of criteria of brain death. CONCLUSIONS: Transcranial Doppler is a good method for confirming the clinical diagnosis of brain death, fundamentally in patients undergoing treatment with drugs depressing the central nervous system. PMID- 8433586 TI - [Drugs predicting hepatic function]. PMID- 8433587 TI - [Errors and problems in the administration of insulin]. PMID- 8433588 TI - [Analysis and commentary on the Abril Martorell report]. PMID- 8433589 TI - [Advantages of oxygen therapy by a transtracheal catheter]. PMID- 8433590 TI - [Regenerative nodular hepatic hyperplasia and scleroderma]. PMID- 8433591 TI - [Infraorbital neuropathy as a manifestation of cancer]. PMID- 8433592 TI - [Oral administration of pancreatic enzymes in the treatment of ascites and pancreatic pleural effusion]. PMID- 8433593 TI - [Arthritis caused by calcium pyrophosphate and articular infection. An exceptional association?]. PMID- 8433594 TI - [Neurology and informatics]. PMID- 8433595 TI - [Leiomyosarcoma of the extremities]. PMID- 8433596 TI - [Ambulatory registration of arterial tension; towards a logical terminology]. PMID- 8433597 TI - [Complete guidelines concerning the sternal syndrome]. PMID- 8433598 TI - [Thoughts during nicotine withdrawal]. PMID- 8433599 TI - [Scant instructions reduce the value of a proposal for a drunk driving law]. PMID- 8433600 TI - [Vitamin K prevention and cancer]. PMID- 8433601 TI - [Limited supply of organs. The great problem of transplantation activities]. PMID- 8433603 TI - [Diagnoses in patients deceased during respirator therapy]. PMID- 8433602 TI - [Organs from deceased persons for transplantation. Increase in demand but not in the number of donors]. PMID- 8433604 TI - [The smoking gun of cardiovascular diseases? The great interest in Lp(a) lipoprotein]. AB - A highly significant association (p < 0.001) was found in 1971-1972 between pre beta-1 lipoprotein and coronary heart disease. Later, pre-beta-1 lipoprotein was in fasting serum samples found to be equivalent to Lp(a) lipoprotein. Continuing structural and clinical studies further documented the high atherogenicity of Lp(a) and revealed probable pathogenetic mechanisms. Interest in Lp(a) has increased tremendously during the last few years due to the recent overwhelming support for an independent association between Lp(a) and atherosclerotic disorders and the revelations of its fascinating structure. The structure of Lp(a), its association with clinical disorders and probable pathogenetic mechanisms are exemplified and discussed in relation to type of developed atheromas, their susceptibility to disruption and the importance of inherited high Lp(a) levels for the thrombotic complications. PMID- 8433605 TI - [A mattress cover relieves mite allergy]. PMID- 8433606 TI - [Smoking and disease. Food can influence the risk]. PMID- 8433607 TI - [Infantile spinal muscular atrophy. An unusual disease with various differential diagnoses]. PMID- 8433608 TI - [The gene of spinal muscular atrophy localized. Possibilities for prenatal diagnosis]. PMID- 8433609 TI - [The men behind the syndrome: Werdnig and Hoffmann. They classified spinal muscular atrophies]. PMID- 8433610 TI - [Torsion of the gallbladder]. PMID- 8433611 TI - [Torsion of a healthy fallopian tube]. PMID- 8433612 TI - [Attitude to animal experiments is seldom directed by facts. The views are more nuanced than in the mass media]. PMID- 8433613 TI - [Medical ethics and religion. Should euthanasia and assisted suicide be permitted?]. PMID- 8433614 TI - [Sick-listing of women. Occupational environment is the cause of substantial increase]. PMID- 8433615 TI - [Good care in stroke demands a well-organized care chain]. PMID- 8433616 TI - [Social psychiatry is destroyed by investigations. Regression to a purely biomedical psychiatry]. PMID- 8433617 TI - [A prescription for better psychiatry]. PMID- 8433618 TI - [It is not about the psychiatric outpatient clinics]. PMID- 8433619 TI - [Peroperative cholangiography is important also in laparoscopic cholecystectomy]. PMID- 8433620 TI - [6,366 pages of unread information]. PMID- 8433621 TI - [Yes, to the system of family physicians!]. PMID- 8433622 TI - [Limited right to change preparations]. PMID- 8433623 TI - [Hand disinfection against nosocomial infections. Important preventive measure]. PMID- 8433624 TI - [A multiresistant hospital bacteria. Measures for prevention of transmission in hospitals]. PMID- 8433625 TI - [Methicillin resistant Staph aureus. Outbreaks prove vulnerability of health care]. PMID- 8433626 TI - [Spinal fractures in Bechterew's disease. Injuries most likely underdiagnosed]. PMID- 8433627 TI - [Postoperative analgesia. Simple methods for improvements exist]. PMID- 8433628 TI - [Follow the prescription! A well-considered choice of drugs is good economy]. PMID- 8433629 TI - [Group therapy for male sex offenders. No recurrence is reported in a follow-up]. PMID- 8433630 TI - [It is not necessary to weigh newborn infants daily at the maternity wards]. PMID- 8433631 TI - Making medical decision making more user-friendly. PMID- 8433632 TI - Reanalysis: recalibration versus replication. PMID- 8433633 TI - Diagnostic reasoning of high- and low-domain-knowledge clinicians: a reanalysis. AB - Thinking-aloud protocols provided by Joseph and Patel were reanalyzed to determine the extent to which their conclusions could be replicated by independently developed coding schemes. The data set consisted of protocols from four cardiologists (low domain knowledge = LDK) and four endocrinologists (high domain knowledge = HDK), individually working on a diagnostic problem in endocrinology. The two analyses agree that the HDK physicians related data to potential diagnoses more than did the LDK group and were more focused on the correct diagnostic components. However, the reanalysis found no meaningful difference between the groups in diagnostic accuracy, speed of diagnosis, or the breadth of the search space used to seek a solution. In the reanalysis, the HDK physicians employed more single-cue inference and less multiple-cue inference. The generalizability of results of protocol-analysis studies can be assessed by using several complementary coding schemes. PMID- 8433634 TI - Developing prediction rules and evaluating observation patterns using categorical clinical markers: two complementary procedures. AB - Substantial uncertainty often remains at the time that important diagnostic or therapeutic decisions must be made, despite the availability of multiple clinical indicators. Multiple indicators may be used to define observation patterns that are associated with the presence or absence of disease. Clinical prediction rules based on groups of observation patterns have been used to quantify probabilities and reduce error rates for some medical problems, but efficient use of multiple indicators remains a major challenge in medical practice. Medical outcomes and clinical observations are frequently categorical. Two statistical techniques appropriate for generating prediction rules from categorical data are logit analysis (LA) and recursive partitioning analysis (RPA). LA and RPA were compared in evaluating observation patterns for fractures among 666 upper-extremity injuries in children, and in developing prediction rules for selective radiographic assessment. Fracture estimates and error reductions provided by RPA and LA were very similar. Each technique generated a set of prediction rules with a range of misclassification probabilities, and evaluated the probabilities of fracture for all observation patterns. LA used more information than RPA in observation pattern evaluations, however, and provided fracture estimates specific to each pattern. With currently available statistical software, RPA output provides better statistical guidance in generating prediction rules, whereas LA provides more statistical information of use in evaluating observation patterns. LA warrants attention similar to that conferred on RPA. It appears that complementary use of LA and RPA would be valuable in developing clinical guidelines. PMID- 8433635 TI - Should Canada and the United States universally vaccinate infants against hepatitis B? A cost-effectiveness analysis. AB - This paper examines the economic attractiveness of universal vaccination of infants with hepatitis B virus (HBV) vaccine by calculating the incremental cost effectiveness of this strategy when compared with the currently recommended strategy of screening all pregnant women and vaccinating only infants born to HBsAg+ mothers. A decision-analytic model involving a Markov process to model the long-term sequelae of HBV infection was constructed to estimate the expected costs and life expectancies for a cohort of newborns under two strategies: the current screening policy (SELECTIVE), which involves active and passive vaccination of infants born to carrier mothers, and a policy that combines the current screening strategy (including active and passive vaccination of infants born to carriers) with active vaccination alone for children of non-carriers (UNIVERSAL). A hypothetical cohort of children born in either Canada or the United States in 1991 was examined. Cost estimates were derived for Ontario. From a societal perspective, the incremental cost required to achieve one extra life year was found to be $30,347, comparable to the cost-effectiveness of other health care strategies commonly used in North America. The result is sensitive to the duration of vaccine effectiveness and particularly to the price of the vaccine. Universal vaccination results in net cost saving at a vaccine price of approximately $7 per dose, from a societal perspective. It is concluded that universal vaccination against HBV in infancy is economically attractive, comparable in cost-effectiveness to existing health care interventions. Lower vaccine prices would substantially improve the attractiveness of such a program. Implementation of universal vaccination should be considered in North America, contingent on vaccine price reduction. A monitoring program to ensure the long term efficacy of the vaccine should be part of such a program. PMID- 8433636 TI - A prototype decision support system for differential diagnosis of psychotic, mood, and organic mental disorders. AB - The authors designed a decision support system to assist mental health professionals to perform differential diagnoses of psychotic, mood, and organic mental disorders in accordance with the American Psychiatric Association's revised third edition of the Diagnostic and Statistical Manual of Mental Disorders. A prototype system arrived at through a rigorous methodology illustrates a style of development that attempts to ensure system maintainability, correctness, and consistency of deduction and promotes high quality in software. PMID- 8433637 TI - Validation of probabilistic predictions. AB - Current advances in high-speed computing and increased availability of statistical software have led to widespread use of statistical methods for the development of computerized protocols predictive of binary health outcomes. If these predictive algorithms are to be used in settings other than those for which they were developed, e.g., applied in a different geographic setting or extrapolated for use in a slightly different population, then they should be carefully validated to ensure appropriate application. Miller et al. (Stat Med. 1991) provided a comprehensive methodology for external validation of logistic prediction models, and applied these methods in a temporal validation setting. In this article, the authors emphasize how these methods can be applied to general forms of probabilistic predictions and provide several SAS macros for computation of the desired statistics. PMID- 8433638 TI - Patients' and physicians' interpretations of graphic data displays. AB - To assess how patients' and physicians' treatment preferences are influenced by graphic data displays (five-year survival curves), a cross-sectional survey of patients, physicians, and medical students was done in a university-based Department of Veterans Affairs Medical Center. Participants in the study were 119 patients seen in a general medicine clinic, 43 physicians, and 67 medical students. Three five-year survival graphs were used. Each graph contained survival curves for two alternative unidentified treatments for an unidentified medical condition. Graph 1 was a baseline graph used in previous studies of framing effects. Graph 2 contained one survival curve having an area under the curve that was 24% greater than that in graph 1. Graph 3 contained one survival curve that had an area under the curve that was 42% greater than that in graph 1. Respondents were asked to indicate which treatment they preferred for each graph and which aspects of the five-year survival curves most influenced their choices. Respondents did not receive numerical data about the difference between the areas under the two curves. Most patients did not change their preferences across the three graphs. A significantly larger (p < or = 0.0001) proportion of physicians and medical students than of patients changed their preferences across the three graphs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433639 TI - Development of an index of maternal transport. AB - The authors used a decision-analytic approach to develop a Maternal Transport Index (MTI) from ACOG guidelines for maternal transport. Data were obtained from three questionnaires administered to five perinatologists, practicing in facilities with various casemixes. Each questionnaire was based on a given level of hospital and contained scenarios describing indications for maternal transport. The MTIs, ratios of the logs of the proportions with given outcomes in Level III hospitals relative to Level I (or II) hospitals, ranged from 1.0 to 26.3 for newborn outcomes. They were greater for Level I hospitals (than Level II) and when newborn outcomes included severe disability as well as death. Within gestational age categories, the MTI was generally greatest for active preterm labor and, within complication categories, for 24-26 or 27-31 weeks' gestation. It was large for maternal outcomes only for two rare acute medical conditions. The MTI has potential use in setting priorities for maternal transport. PMID- 8433640 TI - The effect of context on visual representational momentum. AB - Effects of background context on representational momentum were examined in six experiments. In each experiment, three orientations of a target rectangle undergoing implied rotation (i.e., the inducing stimuli) were presented, and subjects judged whether the orientation of a fourth rectangle (i.e., the probe) was the same as or different from that of the third inducing stimulus. Target rectangles were enclosed within a larger square frame context during induction (i.e., presentation of the inducing stimuli), judgment (i.e., presentation of the probe), or both induction and judgment. If context during induction moved in the same direction as the inducing stimuli or if context during judgment was rotated slightly forward from the orientation of the final inducing stimulus, representational momentum was increased. If context during induction moved in the direction opposite to the inducing stimuli or if context during judgment was rotated slightly backward from the orientation of the final inducing stimulus, representational momentum was decreased or reversed. If context was present during both induction and judgment, direction of representational momentum was biased toward the context at judgment. Implications of context for accounts of representational momentum are discussed, and a tentative model is proposed. PMID- 8433641 TI - Articulatory rehearsal and phonological storage in working memory. AB - The theoretical distinction between an articulatory control process and a short term phonological store was supported in five experiments on immediate serial recall. In Experiment 1, articulatory suppression during the presentation and recall of auditory material abolished the word length effect but not the phonemic similarity effect. In Experiment 2, the two latter effects were found to be independent with auditory presentation. In Experiment 3, the effects of irrelevant speech and word length were found to be independent with visual presentation. In Experiment 4, articulatory suppression during the presentation and recall of auditory material abolished the phonemic similarity effect with a slow presentation rate. Nevertheless, in Experiment 5, articulatory suppression with a conventional presentation rate did not reduce the effect of phonemic similarity, even when a 10-sec interval was interposed between presentation and recall. These results indicate that the encoding, maintenance, and retrieval of spoken material within the phonological store do not depend on a process of articulatory rehearsal. PMID- 8433642 TI - Working memory and strategies in syllogistic-reasoning tasks. AB - It has often been asserted that working-memory limitations are a major factor contributing to problem difficulty; for example, Johnson-Laird's (1983) mental models theory appeals to working-memory limitations to explain the difficulty of syllogistic reasoning. However, few studies have directly explored working memory in problem solving in general or syllogistic reasoning in particular. This paper reports two studies. In the first, working-memory load was varied by presenting syllogistic tasks either verbally or visually (so that the premises were continuously available for inspection). A significant effect of memory load was obtained. In the second study, premises were presented visually for a subject determined time. Dual-task methods were used to assess the role of working-memory components, as identified in Baddeley's (1986) model. Syllogistic performance was disrupted by concurrent random-number generation but not by concurrent articulatory suppression or by concurrent tapping in a preset pattern. Furthermore, the concurrent syllogism task interfered with random generation and to a lesser extent with articulatory suppression, but not with tapping. We conclude that while the central-executive component of working memory played a major role in the syllogistic-task performance reported here, the articulatory loop had a lesser role, and the visuospatial scratch pad was not involved. PMID- 8433643 TI - Associative priming in perceptual identification: effects of prime-processing requirements. AB - Three experiments assessed the effects of prime-processing instructions on associative priming in word identification and episodic memory for primes. In Experiment 1, groups instructed to read the prime silently or generate silently an associate of the prime showed a larger accuracy benefit for related over unrelated targets than did a group that decided whether an asterisk was to the right or left of the prime. The asterisk-search group showed a weaker repetition effect on a subsequent identification test of primes, indicating that the weaker priming in this group was a result of poorer perceptual processing. On a cued recall test for primes, the generate group was superior to the other groups. In Experiment 2, we found that with weak prime-target associations, priming was comparable for read and generate groups and stronger than estimated for a guessing strategy, on the basis of single predictions made from each prime by an additional group. In Experiment 3, we demonstrated that the read and generate instructions produced similar mispriming and inhibitory effects. The results suggest that the depths of prime-processing manipulations do not have parallel effects on priming and episodic memory, and that associative priming in word identification, as in other tasks, may involve an expectancy process. PMID- 8433644 TI - Mental image reversal and verbal recoding: when ducks become rabbits. AB - A recent debate has concerned whether classical bistable configurations (e.g., duck/rabbit) can be reinterpreted using mental imagery. Research in this field indicates that image reversal is possible only when subjects change their specification of orientation. In a series of four experiments, we demonstrate that mental reversal of classical bistable configurations (CBCs) is impeded by verbally recoding the visual pattern at the time of input. When subjects were prevented from verbally recording visual stimuli in short-term memory, they fared systematically better in mentally reversing the CBC, even when they received no instructions to change their reference frame or specification of orientation. On this basis, we suggest a model of image reversal that takes into account the interaction between memory codes and provides a new perspective on verbal recording, verbal overshadowing, and mental discoveries. PMID- 8433645 TI - Design controversies and the generation effect: support for an item-order hypothesis. AB - We performed three experiments to investigate an earlier finding of Nairne, Riegler, and Serra (1991) that item generation disrupts the long-term retention of serial order. Experiment 1 demonstrated a clear advantage of reading over generating on a reconstruction test when reading and generating occurred in pure, but not mixed, lists. Experiment 2 showed that the standard generate advantage is seen in free recall of mixed, but not pure, lists, even when recall is immediately followed by reconstruction of serial order of the same items. Experiment 3 replicated Experiment 1, but with the use of an incidental learning procedure. The results of all three experiments are consistent with the claim that generation has dissociative effects on item and order memory; moreover, these dissociative effects help to explain design controversies in the generation effect literature. PMID- 8433646 TI - Part-instance association in the categorization of acts. AB - Rips and Conrad (1989) found a kind-part reciprocal effect in models of the mind, in that one mental activity is part of another if the second is a kind of the first, and vice versa. In the present paper, we hypothesize that a formally analogous effect occurs at the level of activity instances. In particular, we hypothesize that an act is judged to be an instance of an act category referred to by an activity verb if the activity is judged to be an important part of the act, and vice versa. Empirical support for this hypothesis is found in three studies with activity verbs. The converse part-instance relation is further noted to parallel the part-instance association for a specific type of metonymically defined categories. Rips and Conrad's kind-part reciprocal effect is shown to be a logical consequence of the converse part-instance relation. PMID- 8433647 TI - Hypermnesia in free recall and cued recall. AB - In three experiments, categorized lists and both free recall and cued recall tests were used to examine hypermnesia. In Experiment 1, materials were drawn from obvious and nonobvious categories in an attempt to vary the amount of relational processing at encoding. The study materials in Experiment 2 consisted of a long word list that comprised several exemplars from each of a number of common categories. In Experiment 3, a single exemplar was drawn from each of 45 categories. In each experiment, similar magnitudes of hypermnesia were obtained on free and cued recall tests. Examination of the specific items recalled across tests indicated that similar processes underlie the hypermnesic effect for both test conditions. Implications of the results for extant accounts of the hypermnesic effect are discussed. It is concluded that the dynamics of retrieval processes change in a systematic fashion across repeated tests and the retention interval following study and that an adequate account of the nature of these changes in retrieval dynamics is essential to our understanding of hypermnesia and related phenomena. PMID- 8433648 TI - Examining a processing tradeoff explanation of proactive interference. AB - Burns (1989) claims that proactive interference effects occur in paired-associate learning because of tradeoffs in relational and response-specific processing. Consistent with this claim, Burns demonstrated that free recall of critical-list responses is better in the interference condition than in the control condition. Burns's processing tradeoff explanation predicts that the occurrence of this reverse-interference effect should be positively correlated with the occurrence of traditional interference effects. We present several experiments whose results are inconsistent with this prediction. We hypothesize that the reverse interference effect is a list-length effect. The results of a final experiment, contrasting the predictions of the list-length and processing tradeoff explanations, support the list-length explanation. PMID- 8433649 TI - Limits of the processing view in accounting for dissociations among memory measures in a clinical population. AB - In three experiments, we examined the performance of patients with schizophrenia on implicit and explicit memory tests that have been shown to involve predominantly data-driven or predominantly conceptually driven processes. In Experiment 1, we compared the implicit tests of category production (conceptually driven) and word identification (data driven) and found that schizophrenic patients' performance on these tests did not differ from that of normal subjects. In Experiment 2, a comparison of the category-production and explicit cued-recall tests, both of which involve conceptual processes, showed that schizophrenic patients were impaired on the cued-recall test but not on the category-production test. In Experiment 3, a comparison of the word-identification and explicit graphemic cued-recall tests, both of which involve data-driven processes, showed that patients were impaired on the cued-recall test but not on the word identification test. The results of both Experiments 2 and 3 revealed a dissociation between implicit and explicit test performance under conditions in which the two tests involve similar types of processes. These results support theoretical views that distinguish implicit from explicit modes of retrieval. PMID- 8433650 TI - Age differences in implicit memory: more apparent than real. AB - Elderly subjects and a group of young subjects identified fragmented picture sequences under conditions of focused attention. Two other groups of young subjects carried out this task under divided-attention conditions. Implicit memory, as measured by item-specific savings, was found in all groups, but this effect was smaller in the elderly group. The young subjects, but not elderly subjects, performed better on new items. The divided-attention conditions equated recall and recognition by the young and the elderly, but only the young subjects showed greater savings for recalled items. The elderly subjects' reduced implicit memory therefore stemmed from their inability to facilitate implicit memory with explicit memory. A second experiment, involving only young subjects tested after delay, produced findings similar to those for the young divided-attention subjects. Implicit memory, as measured by savings in picture completion, does not show an age-related change when the role of explicit memory is considered. Age does, however, reduce skill learning. PMID- 8433651 TI - Perceptual grouping in visual word recognition. AB - Four experiments are presented in which printed texts are read for their meaning. Some of the texts were mutilated by altering the size of selected letters. In Experiments 1, 2, and 3, the number of words mutilated per passage and the number of letters changed per word were both manipulated. In all three experiments, reading was slowed as a function of the number of words changed per passage, while the number of letters changed per word had a much smaller effect. The interaction between the number of words and number of letters changed was not significant in any of the experiments. It is difficult to explain these results merely in terms of changes in the discriminability of letters. In Experiment 2 all uppercase text was used, which argues against an explanation in terms of supraletter features such as word envelope. We propose an explanation in terms of visual attention and the perceptual grouping required prior to feature recognition. The last experiment supports this explanation through the counterintuitive finding that adding letters of intermediate size can improve legibility by allowing grouping processes to associate large and small letters as belonging to the same word object. PMID- 8433653 TI - The changing medical profession: implications for medical education. A world conference. PMID- 8433652 TI - Remembering and knowing: two means of access to the personal past. AB - The nature of recollective experience was examined in a recognition memory task. Subjects gave "remember" judgments to recognized items that were accompanied by conscious recollection and "know" judgments to items that were recognized on some other basis. Although a levels-of-processing effect (Experiment 1) and a picture superiority effect (Experiment 2) were obtained for overall recognition, these effects occurred only for "remember" judgments, and were reversed for "know" judgments. In Experiment 3, targets and lures were either preceded by a masked repetition of their own presentation (thought to increase perceptual fluency) or of an unrelated word. The effect of perceptual fluency was obtained for overall recognition and "know" judgments but not for "remember" judgments. The data obtained for confidence judgments using the same design (Experiment 4) indicated that "remember"/"know" judgments are not made solely on the basis of confidence. These data support the two-factor theories of recognition memory by dissociating two forms of recognition, and shed light on the nature of conscious recollection. PMID- 8433654 TI - Experiences with a method for obtaining feedback on a medical curriculum undergoing change. AB - Successful innovation and change in the way medical students are prepared are notoriously difficult. The relationship between the administrative structures of the medical school and its teaching hospitals, other responsibilities of its teachers and administrators, and the intricacies of the curriculum as a system of interrelated components, mean that any real change has wide repercussions. An opportunity for evaluation of a curriculum undergoing change was presented at the University of New South Wales, when the Faculty of Medicine introduced a new 6 year medical curriculum in 1988. The change was made to address a number of problems experienced with the old 5-year curriculum. The Course Evaluation Committee was in a unique position to conduct an ongoing evaluation of the new curriculum, year by year, as it was being introduced. A method for obtaining feedback from both staff and students on a medical curriculum undergoing change, is described. While some sample results are presented, the paper concentrates on the advantages and disadvantages of, and our experiences with, this method. Advantages include the specificity and timing of the information collected, and the high response rate. One disadvantage was the repeated use of the same cohort of students. Some staff still perceived the evaluation process as a threat, or were sceptical about the value and validity of student feedback. Whether staff acknowledged ownership of the new curriculum also affected the use of feedback. PMID- 8433655 TI - Student selection: are the school-leaving A-level grades in biology and chemistry important? AB - This study determined the relationships of grades in A-level biology and chemistry with examination success or failure during the medical course. By inspection of medical student records, A-level grades at entry to medical school and examination performance were obtained for 128 (91%) of the students who sat their final MBBCh examination at the University of Wales College of Medicine in June 1988. The majority, 92 (72%), completed their medical school careers with no professional examination failures; 15 failed examinations just in the period up to 2nd MB; 11 failed examinations in the clinical period only and 10 failed examinations in both periods. Whereas grade achieved in A-level chemistry was not associated with undergraduate examination performance, students with a grade A or B in A-level biology were less likely to have problems than the others (21% compared with 47%; the difference of 26% has a 95% confidence interval of 7% to 44%). Specifically, there appears to be a strong relationship between a low grade in biology and difficulties in the preclinical examinations. Moreover, for those who have difficulties at this stage, this association continues later in the course. PMID- 8433657 TI - Medical education in a multilingual and multicultural world. PMID- 8433656 TI - The moral development of medical students: a pilot study of the possible influence of medical education. AB - Medicine endorses a code of ethics and encourages a high moral character among doctors. This study examines the influence of medical education on the moral reasoning and development of medical students. Kohlberg's Moral Judgment Interview was given to a sample of 20 medical students (41.7% of students in that class). The students were tested at the beginning and at the end of their medical course to determine whether their moral reasoning scores had increased to the same extent as other people who extend their formal education. It was found that normally expected increases in moral reasoning scores did not occur over the 4 years of medical education for these students, suggesting that their educational experience somehow inhibited their moral reasoning ability rather than facilitating it. With a range of moral reasoning scores between 315 and 482, the finding of a mean increase from first year to fourth year of 18.5 points was not statistically significant at the P < or = 0.05 level. Statistical analysis revealed no significant correlations at the P < or = 0.05 level between the moral reasoning scores and age, gender, Medical College Admission Test scores, or grade point average scores. Along with a brief description of Kohlberg's cognitive moral development theory, some interpretations and explanations are given for the findings of the study. PMID- 8433658 TI - How ambulatory care is different: a paradigm for teaching and practice. AB - This paper reviews the issues regarding an increased emphasis on medical education and practice in the ambulatory care setting. A paradigm for ambulatory medicine is offered which combines the elements of 'traditional' medical care and teaching with the more 'distinctive' elements representative of the ambulatory setting. The former includes aetiology, history, physical examination, laboratory tests and therapy; while the latter includes continuity, context, health education, economics and responsibility. The paradigm is illustrated in relation to the problem of hypertension. The ambulatory medicine paradigm is further discussed with respect to potential barriers to its acceptance. These include: (1) the assumption that 'traditional' medical education does teach all 10 elements of the paradigm; (2) the axiom that if one learns to care for the sickest patients, the less ill ones should be manageable; (3) the intuitive aspects of the 'art' of practising ambulatory medicine; (4) the recognition that this teaching will require a longitudinal experience; and (5) perception that the five distinctive elements are not 'hard' science and objectively measurable. Nevertheless, the changing face of medical practice requires the adoption of an ambulatory medicine paradigm in medical education. PMID- 8433659 TI - Subjective and behavioural evaluation of the teaching of patient interview skills. AB - One aim of the course in general practice and public health medicine during the final year at the University of Sheffield is to help students to develop further their interpersonal communication skills with particular reference to their skills in interviewing patients. During the course students meet twice in small groups with a tutor in order to review audiotape recordings of interviews with patients seen during their general practice attachments. The main activity during these tutorials is group discussion of the interviewer's behavioural options at significant points during the interview. Students also listen individually with a tutor to an interview that they have recorded, discuss this interview and assess it against a set of explicit criteria as part of their summative course assessment. In response to an anonymous end-of-course questionnaire, 85% of students felt that their interview skills had been improved by the teaching and 68% that listening to their own recordings had been the most helpful aspect. During interviews with simulated patients recorded at the end of the course, students asked more open questions, fewer questions referring to physical symptoms, more questions referring to feelings, beliefs or behaviour and fewer questions of a check-list type than during interviews recorded at the start. A number of students also requested examples of specific events during the end-of course interviews although none had done so at the beginning of the course. All of these changes were statistically significant and were in directions that were consistent with the teaching in the small-group tutorials. PMID- 8433660 TI - Clinical tutor evaluation: a 5-year study by students on an in-patient service and residents in an ambulatory care clinic. AB - Medical students on an in-patient service and residents working in an ambulatory care clinic have regularly evaluated their clinical tutors over the 5 years 1985 1989. Both groups of raters reliably and predictably evaluated their tutors and both emphasize between-tutor comparisons more than actual rating values for individual tutors. Tutors active in both contexts regularly receive higher ratings from the medical students than from the residents. Mid-course feedback to tutors in the medical course had no impact on end-of-course ratings. In neither context did tutor ratings improve from one evaluation to the next. Both groups reliably discriminate between the teaching skills and the personality traits of individual tutors. PMID- 8433661 TI - Residents' perceptions of their teachers: facilitative behaviour and the learning value of rotations. AB - Despite changes in modern medicine the role of the clinical teacher remains central to medical residents' education and rotations continue to be their dominant educational context. Residents have strong positive feelings for clinical teachers who are perceived as interested in teaching and for those rotations that provide a balance of educational opportunities and patient care responsibilities. Research in residency education has focused on teacher behaviours used to teach medical residents clinical information or patient care skills but has neglected teacher behaviours used to facilitate effective learning relationships with residents. To explore the impact of clinical teachers' use of facilitative behaviours on residents' educational experience, we use concepts stemming from the psychologist Carl Rogers' work previously shown to be associated with positive learning outcomes--empathy, unconditional positive regard, and congruence. These constructs are measured by the use of the four scales of the Barrett-Lennard Relationship Inventory (BLRI)--level of regard, unconditionality of regard, congruence and empathy. Our study measures the correlation between residents' perceptions of clinical teachers' use of facilitative behaviours and residents' evaluation of the learning value of rotations. Thirty-three residents completed the BLRI on a different clinical teacher for each of six monthly rotations. A total of 158 surveys were returned. There were strong positive correlations between three of the BLRI variables and residents' perception of the learning value of rotations. Potential uses of these findings are discussed. PMID- 8433662 TI - Medical training and English language proficiency. AB - Concern is often expressed about the English language proficiency (ELP) of students engaged in professional training. This report assesses the ELP of the 1990 and 1991 intakes into medicine at the University of Sydney. A quick screening test and individual in-depth tests were used in a two-stage design. Admission to the course is highly competitive and most students are selected from the top 0.75% of Higher School Certificate results but 15% and 19% of the year cohorts were found to be below average in ELP. English proficiency was found to be consistently correlated with first- and second-year university results. Initiatives taken to support students with language disadvantages and to ensure that graduates will be able to communicate effectively with patients are outlined. PMID- 8433663 TI - A model for clinical teaching and learning. AB - A set of criteria to observe clinical teaching was developed and used to describe and evaluate the teaching behaviour of 24 tutors of medical students in their initial clinical skill term. The tutors had no previous instruction in teaching techniques, nor had their teaching been previously evaluated. The criteria used focus on six basic dimensions: the teaching/learning environment; the degree of intellectual challenge; the degree of interaction; the logical structure of teaching sessions; the quality of teaching skills; and the modelling of professional skills and attitudes. A continuum of teaching behaviour was observed in each dimension, with most tutors demonstrating adequate levels of performance in each. The tutors all strongly supported the evaluation and the feedback they received. Their subsequent teaching behaviour will be reviewed to assess the impact of this feedback. PMID- 8433664 TI - Two models of primary health care training. AB - In 1991, the Fiji School of Medicine restructured the training of its medical students, dividing the 7-year course into two phases. Students now undertake a 3 year community-oriented primary care practitioners course, after which they may elect to continue practice in a primary health care role, or to undertake further hospital-based training to complete their medical degree. The course responds to the health needs of the South Pacific, and the local patterns of morbidity and mortality, rather than measuring itself against the curricular demands of its more developed neighbours, Australia and New Zealand. At the same time, the Tropical Health Program of the University of Queensland Medical School responded to demands from the Aboriginal and Torres Strait Islander community to develop primary health care training at degree level. This was intended to complement other strategies undertaken by the Aboriginal and Torres Strait Islander Studies Unit such as the recruitment and support of indigenous students through mainstream health professional education. There was a need to address health priorities that are very different to those of the Australian population as a whole, as well as the sociopolitical and cultural context as it affects both students themselves and health issues in their communities. Both institutions have chosen problem-based teaching/learning as appropriate to their courses, and content is also similar, though with emphases that reflect the differing contexts. The two courses are examples of innovative responses by centres with university medical faculties to specific issues in health education. PMID- 8433665 TI - Training immigrant doctors: issues and responses. AB - An unprecedented wave of immigration of doctors to Israel, mainly from the former Soviet Union, posed for Israeli health leaders the problem of bringing them to a common and accepted Western level of performance. Stemming from the deep commitment which Israel has towards the immigrants, the state offers them a training opportunity to enhance their chances of being licensed and finding jobs in their profession. A 6-month programme was launched by Ben-Gurion University, later adopted by other medical schools and supported by the Government of Israel. The programme was designed to provide effective responses to the specific problems of the immigrant population, which are: lack of knowledge of local language, both everyday and professional; overspecialization in too narrow specialties; possession of clinical specialties which do not exist in the new country; insufficient updating in medical sciences and technology; unawareness of economic implications of health care; difficulty in originating new solutions to clinical problems, and lack of skill in answering objective test items. The programme is characterized by a protective environment, problem-oriented learning, small-group activities and emphasis on learning languages. The clinical problems are designed to emphasize the general practitioner's point of view of both common and emergency situations. The programme has achieved its goals, as judged by the success rate of its graduates in the National Licensing Examination as compared with the success of immigrant doctors who chose not to participate in the training.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433666 TI - An educational model for medical appointments. AB - A model of planned appointments to the training and consultant grades in the National Health Service is proposed. Contracts in each grade would begin and end at fixed dates. The aim of the model is to provide a coherent educational and career plan for each doctor with minimal disruption of the clinical service. It is proposed that a phased introduction of the scheme would allow the process of change to be acceptable and the model to be evaluated before a commitment to its full introduction is made. PMID- 8433667 TI - Improving the quality and ease of tracking invasive procedures. AB - Documentation of the decision-making process leading up to an outcome of procedures is essential for assessing quality of patient care, supporting reimbursement, determination of appropriate utilization, and discernment of practitioner competence. Currently, doctors document interventions conducted outside the operating room in narratives within the daily progress notes. The free-form narrative typically includes the practitioner directly involved, procedure performed, technique used and outcomes. While hospitals encourage conformity to these documentation standards, the quality and content of the narratives vary greatly by practitioner, frequently leaving significant information missing. Therefore, to improve both quality of documentation in procedure notes and ease of monitoring non-operating room procedures, we developed a multicopy standardized procedure note. The form contains lines for recording the type, location, indication, anaesthesia, findings, and complications of the procedure, plus the persons performing, supervising and undergoing the procedure. Practitioners complete the multicopy note instead of the usual narrative note. We encode all the information from the standardized note into a data base that accumulates information on all procedures done throughout the hospital. The data base is used to generate summary reports to provide feedback to residents, residency directors and practitioners on procedural proficiency. The major advantage of this system is that it simultaneously improves the quality of documentation and ease of tracking non operating room procedures at our hospitals. In addition, the system collects the information needed for reimbursement coding, hospital quality assurance and utilization review, and practitioner and resident credentialling purposes. PMID- 8433668 TI - The use of hypertext: demonstration of the methods for investigating an epidemic of meningitis. AB - The Meningitis Hypertext Case Study is a computer-assisted learning module developed by the Liverpool Epidemiology Programme as part of a comprehensive set of modules and case studies to assist health workers to learn epidemiology. The objectives of the case study are to highlight important concepts in diagnosing an epidemic of meningitis. It has been developed using hypertext software (LINKWAY) which allows interactions with other epidemiological software (EPI INFO) for the analysis of the data. The case study makes extended use of graphical displays, has a 'user-friendly' presentation and can be used by individuals and groups. Our initial experience indicates that this form of computer-assisted learning has considerable potential by providing users with an organized path through a series of problems set in a realistic environment. This could prove to be potentially useful in developing countries where up-to-date learning materials are often unavailable. PMID- 8433669 TI - An early 'clinical trial' as a teaching exercise: the Book of Daniel 1.1-15 (1.1 20). AB - This article discusses a very early clinical trial from the Old Testament. One of Daniel's and his companions' tribulations in Babylonia is explicated within the framework of the modern clinical trial. Even if many, or maybe even most, guidelines for good clinical trial practice are violated (it can even be argued that this is not really a clinical trial), a discussion of this biblico historical episode in, for example, a problem-based course in (clinical) epidemiology or a course in the critical appraisal of the literature, can be a useful (and possibly entertaining) exercise. PMID- 8433670 TI - [Ethics committees]. PMID- 8433671 TI - [Fungal infections of man. Part 6: Mycoses in infancy and early childhood]. PMID- 8433672 TI - [Malignant hyperthermia. Physiologic and genetic principles]. PMID- 8433673 TI - [Eosinophilic granulocyte-associated diseases. Current aspects of pathogenesis and therapy]. PMID- 8433674 TI - Choice of cholesterol-lowering drugs. PMID- 8433675 TI - Effective multi-agent chemotherapy for advanced abdominal lymphoma and FAB L3 leukemia of childhood. AB - Between June 1981 and May 1988, 51 children with diffuse undifferentiated, advanced (Murphy Stage III and IV) intra-abdominal non-Hodgkin's lymphoma were treated on an intensive multi-drug chemotherapy protocol without irradiation to the primary tumour. Therapy was completed for Stage III disease at one year, but Stage IV patients continued with a further year of therapy until January 1986, when it was reduced to one year. Central nervous system (CNS) prophylaxis consisted of eight doses of intrathecal MTX for all children, and 24 Gy cranial irradiation for Stage IV patients only. There were 42 patients with Stage III disease (III A n = 29 and III B n = 13) and nine patients with Stage IV disease, of whom eight had extensive bone marrow and extramedullary disease (FAB L3 ALL). No patient had CNS disease at presentation. Forty-eight of 51 children (94%) achieved a complete remission. Two children died during remission induction therapy and eleven children relapsed, mostly within eight months of diagnosis. All patients have completed therapy. Failure free survival is 76% for Stage III and 67% for Stage IV patients, with a median followup of 90 and 64 months, respectively. Subdividing Stage III patients into Stage III A and III B did not show significantly different survival (P = 0.9), but the number of patients in Stage III B is small. These results compare favourably with the most effective published protocols, and toxicity has been manageable. PMID- 8433676 TI - Multifocal synchronous osteosarcoma: the Scottish Bone Tumour Registry experience. AB - We report 3 cases of multifocal synchronous osteosarcoma constituting 1% of osteosarcoma cases in the Scottish Bone Tumour Registry over 30 years. All were children and had a median age of 10 years. They all presented with multiple bony lesions in the absence of demonstrable pulmonary metastases. Treatment was with palliative radiotherapy in two and combination chemotherapy and radiotherapy in the most recent case. Survival was poor in all cases, with a median of 7 months. A proposal is made for genetic studies in future cases to help elucidate the origin of these tumours. The multicentric and metastatic hypotheses are discussed. PMID- 8433677 TI - Prophylactic cranial irradiation increases the risk of testicular damage in adult males surviving ALL in childhood. AB - By combining three series of Scandinavian patients, we were able to compare the late testicular sequelae in 41 adult males whose therapy had included chemotherapy alone or chemotherapy with cranial irradiation without other radiotherapy for ALL in childhood. In multivariate analysis, cranial irradiation was associated with a decrease of 5.7 (95% confidence limits 1.5-9.9) cm (P = 0.010) in height, and a decrease of 4.8 (0.3-9.2) ml (P = 0.036) in testicle size. Cyclophosphamide was associated with increases of 8.2 (-0.5-16.9) (P = 0.065) and 3.9 (0.3-7.4) U/L (P = 0.036) in serum FSH and LH concentrations, respectively. Of the 12 patients who had received both cranial irradiation and cyclophosphamide therapy, 4 (33%) had delayed pubertal development as compared with 1 (3.5%) of the other 29 patients (P = 0.008). Patients 12-16 years of age at diagnosis had larger testicles (P = 0.051) and higher testosterone concentrations (P = 0.026) than others. Neither sexual activity nor semen findings correlated with the preceding treatment. Our data indicate that prophylactic cranial irradiation may be associated with impaired growth and pubertal development in boys with ALL. PMID- 8433678 TI - Granulocytic sarcoma. PMID- 8433679 TI - Ewing's sarcoma in a child with human immunodeficiency virus (type 1) infection. AB - A male child with vertically transmitted human immunodeficiency virus type 1 (HIV) infection developed a Ewing's sarcoma of the left fibula at 6.1 years of age. We report the antitumour chemotherapy given and the response of the tumour. Six months after tumour diagnosis the child died of probable HIV encephalopathy. This is the first reported case of Ewing's sarcoma in an HIV-infected child. PMID- 8433680 TI - Intracerebral recurrence of primary intrathoracic rhabdomyosarcoma. AB - We present two cases of intracerebral recurrence of primary intrathoracic rhabdomyosarcoma, occurring within 2 months of each other. Both had embryonal histological features. One (case 1) almost certainly arose within the lung adjacent to a developmental cyst; the intrathoracic site of origin of the other (case 2) was difficult to ascertain. Both were treated on SIOP MMT protocols. The intracerebral deposits became clinically apparent soon after completing chemotherapy. They were removed surgically and second-line chemotherapy was given both systemically and intrathecally. Neither received radiotherapy. The disease recurred in both children whilst on therapy and they died as a consequence of raised intracranial pressure. PMID- 8433681 TI - Recurrent neuroendocrine (Merkel cell) carcinoma of the skin presenting as marrow failure in a man with systemic lupus erythematosus. AB - Neuroendocrine carcinoma of the skin, Merkel cell carcinoma, is an aggressive malignancy with a high incidence of local recurrence and metastasis. We describe a case of neuroendocrine carcinoma of the skin with unusual metastatic spread to the bone marrow in a 55-year-old man with systemic lupus erythematosus. Following resection of a left temporal subcutaneous nodule and complete left parotidectomy and radical lymph node dissection, the patient presented with pancytopenia. Although focal bony metastatic disease was not identified, his bone marrow was diffusely replaced by metastatic carcinoma. High-dose chemotherapy allowed a brief remission; however, the patient subsequently died with central nervous system metastases. PMID- 8433682 TI - Cutaneous squamous cell carcinoma following treatment for acute lymphoblastic leukaemia. AB - The importance of second malignant neoplasms following successful treatment of childhood malignancy is of concern to all professionals involved with the care of these patients. We present an 18 year old patient with a squamous cell carcinoma of his lower lip following prolonged treatment for acute lymphoblastic leukaemia in childhood. The rarity of this tumor in this age group and the aetiological factors involved in developing the second malignancy are discussed. PMID- 8433683 TI - Alveolar rhabdomyosarcoma with the t(2;13): cytogenetic findings and clinicopathologic correlations. AB - We describe here the clinical and pathologic features associated with a specific translocation, t(2;13), in alveolar rhabdomyosarcoma. Tumor specimens from 14 patients with a t(2;13)-positive alveolar rhabdomyosarcoma were studied for cytogenetic-clinicopathologic correlations. Three patients had occult primary tumors; nine patients had primary tumors of the trunk (mediastinal, pelvic, or rectal). The presence of the t(2;13) was ascertained from examination of tumor involved bone marrow in ten patients who had widespread metastatic disease at the time of diagnosis. Marrow involvement was so extensive in three cases that they were initially diagnosed as acute leukemia. Response to therapy was poor, with only five patients achieving a complete response. Twelve patients have died of their disease at a median survival time of 6 months from diagnosis and one is living with recurrent disease; only one patient survives free of disease. PMID- 8433684 TI - Local failure in childhood rhabdomyosarcoma and undifferentiated sarcoma: prognostic factors and implications for curative therapy. AB - In this retrospective review, the risk factors for local failure in childhood rhabdomyosarcoma and undifferentiated sarcoma were assessed in 49 patients managed by a multi-disciplinary team at the Prince of Wales Children's Hospital, Sydney, between 1970 and 1988. Average follow-up time was 6.1 years. Sixteen of 49 patients experienced local failure defined as local recurrence after complete excision (5/20) or progressive local disease following incomplete resection (11/29). Fourteen of 16 patients who experienced local failure have died. Using logrank analysis of time to local failure, we found significantly increased risk with "non-embryonal" histology (P = 0.032), residual tumour (P = 0.052, higher IRS group (P = 0.088), "inadequate radiotherapy" for residual tumour (P = 0.001), delay in definitive local treatment (P = 0.038) and Adriamycin-containing chemotherapy (P = 0.017). When these factors were examined by multivariate analysis (Cox regression), only the presence of residual tumour after resection, "inadequate radiotherapy" for residual tumour (P < 0.001), and delay in definitive local therapy (P < 0.037) were shown to have independent significant association with local failure. We conclude that local failure may be avoided by prompt local treatment by either complete surgical resection or adequate radiotherapy. PMID- 8433685 TI - Neuroblastoma: a 32-year population-based study--implications for screening. AB - This paper describes a retrospective population-based study of neuroblastoma in the West Midlands Health Authority Region--childhood population 1.12 million (OPCS, census 1981)--in which 239 cases were diagnosed between 1st January 1957 and 31st December 1988. The age standardised rate of tumour incidence has remained constant at 7.2 cases per million children per year. The median age at diagnosis was 2 years with 18% of children presenting before the age of 6 months. Fifty children (21%) presented before the age of one year, and for this group of children, the prognosis has improved significantly over the 32-year period (10 year survival increasing from 63% in 1957-67 to 87% in 1978-88), whereas for the 189 (79%) children who presented after one year of age, the prognosis has remained very poor during the study period (10 year survival 1957-67 = 9.5%, 1978 88 = 8.5%). This study supports the need for a prospective study of mass screening at several intervals rather than only at 6 months of age. PMID- 8433686 TI - The favor. PMID- 8433688 TI - Deficits in AIDS/HIV knowledge among physicians and nurses at a Minnesota public teaching hospital. AB - We administered a questionnaire pertaining to recent gains in knowledge about HIV/AIDS treatment and natural history in mid-1990 to all physicians and nurses at a 455-bed public teaching hospital. Surveys were returned by 127 physicians (46%) and 541 nurses (77%). Responses indicated that only 37% of physicians and 18% of nurses knew that the risk for an AIDS-related opportunistic infection becomes significant when the T-helper cell count falls below 200 cells per cubic millimeter. One-fourth of physicians (23%) and more than one-half of nurses (55%) were not aware that the HIV enzyme immunoassay test alone is insufficient to properly determine a patient's HIV serostatus. The survey results revealed a broad deficit in knowledge about the natural history and treatment of HIV infection and demonstrated the need for a clinically relevant core HIV/AIDS knowledge curriculum and for strategies to better educate health care providers to improve care given to HIV-infected patients. PMID- 8433687 TI - State 'laboratories' test health care reform solutions. AB - Widely recognized by the states as a pressing policy issue, health care reform appears to have moved up on the national policy agenda as well. President Clinton has promised to address the issue during his first 100 days in office. Previously, however, the federal government has been deadlocked on health care reform, leaving the states to become the laboratories for developing and testing proposed solutions to our health care crisis. By passing MinnesotaCare in last year's legislative session, Minnesota joined the growing number of states attempting to provide access to affordable, quality health care to their citizens. PMID- 8433689 TI - Clinics without walls. Alternative practice structures for physicians in independent practice. AB - Clinics Without Walls will function as integrated medical practice business organizations for the purpose of carrying out ventures approved by their boards of directors, including the delivery of patient care services under contract to managed care organizations or others. The networks will be responsible for receiving revenue for contracted services and for paying expenses. Patient care should be enhanced by this structure, which will result in improved communications and information exchange among participating physicians and greater patient access to convenient, decentralized medical facilities. Patients and physicians will likely benefit from the expanded services made available through shared network resources. As mentioned above, the MMA and the Hennepin and Ramsey county medical societies are currently developing a detailed Clinics Without Walls prototype that will be made available for implementation during the first half of 1993. PMID- 8433690 TI - The organization of clinics without walls. Legal considerations. PMID- 8433691 TI - Workers' compensation system gets needed overhaul. But will it be enough? PMID- 8433692 TI - Physicians find good retirement plans attract better employees. PMID- 8433693 TI - Medical care accountability. Should physicians be immune? PMID- 8433694 TI - House of medicine must unite to shape health care reform. PMID- 8433695 TI - Live virus shows promise as AIDS vaccine. PMID- 8433696 TI - Cookbook medicine invites malpractice suits. PMID- 8433697 TI - Working together to improve rural EMS. PMID- 8433698 TI - National health care reform tops AMA agenda. PMID- 8433699 TI - Congenital diaphragmatic hernia: Part I. AB - The infant with a congenital diaphragmatic hernia presents many challenges to those caring for him. A thorough understanding of both anatomic and physiologic components can enable the caregiver to accurately assess the patient and employ interventions which will minimize complications. This article discusses the incidence, mortality, embryology, diagnosis, pathophysiology, and conventional management. Part II will discuss alternatives to conventional management, outcome predictors, current research, and follow-up of the infant with a congenital diaphragmatic hernia. PMID- 8433700 TI - The benefits of home care for sick premature infants. AB - The care of sick premature infants at home is evaluated in terms of the benefits related to the health outcome of infants. The home care was provided by trained pediatric nurses through a service-oriented community agency. Pediatric nurses delivered home care 24 hours or less to sick very low birth weight infants discharged from the neonatal intensive care unit in lieu of continued hospitalization. Nursing care at home is described along with a sample nursing care plan for an infant with bronchopulmonary dysplasia. The efficacy of home care on medical utilization indicated that there were less hospitalizations, emergency room visits, and visits to the specialty clinics than previously reported in the literature. Home visitation appeared to improve the health of high-risk premature infants, is cost effective, and may be less stressful for parents. PMID- 8433701 TI - Enhancing regional perinatal care: a clinical traineeship for perinatal nurses in a predominantly rural area. AB - This article describes the objectives, content, teaching strategies, and evaluation methods for the Rural Perinatal Traineeship Program (RPTP). The RPTP is a five-day outreach education program sponsored by The Children's Hospital, Denver for perinatal RNs in the Rocky Mountain, western Great Plains region. The program emphasizes nursing assessment, recognition, stabilization, and transport of the high-risk pregnant woman and sick newborn. The goal is to enhance the nursing care of pregnant women and newborns provided by community hospital RNs by increasing knowledge, reviewing equipment, and updating care practices/skills. To assess effectiveness of the RPTP, participants took a pre, post, and follow-up test. Additionally, follow-up questionnaires, which identified changes in care practices and equipment acquisition, were sent at three different intervals to 299 nurses who participated from 1980-89 and their nursing directors. Overall, 105 participants (36 percent) and 110 of the 127 nursing directors (86 percent) responded to the questionnaire. Results from 86 participants who took all three tests indicated an increase in pre- to post-test scores from 76 percent to 89 percent (p < .001). Follow-up test scores averaged 85 percent (p .001). According to the nursing directors, participants suggested changes in 136 care practices, with 77 percent implemented; and 68 pieces of equipment of which 90 percent were acquired. Suggestions from past participants and nursing directors continue to influence the RPTP in the 1990s. PMID- 8433702 TI - Back transport: exploration of parents' feelings regarding the transition. AB - The purpose of this qualitative study was to explore parents' perceptions and the concepts involved in their preterm infant's back transport from a tertiary neonatal intensive care unit to their home community hospital. A convenience sample of fourteen parents were interviewed five to seven days after the back transport. Following data collection, the analysis of the parents' perceptions regarding the back transport of their premature infant identified a crisis theme that was influenced by several concepts. The subject's positive or negative meaning of the back transport during the pre-crisis phase defined the extent of the crisis during a three day transition period which led to an acceptance of events in the resolution phase. The subjects' perceptions of the previous events of hospitalization and communication of information regarding back transport influenced the meaning of the back transport for them. The extent of crisis during the transition phase was influenced by subjects' perceptions of medical complications, caretaking practice changes, environmental changes, feelings of powerlessness or empowerment, personal coping resources, and support systems available. Resolution in all cases occurred with an acceptance of events. Implications for practice and future research can be identified such as developing and testing education programs to prepare parents for the transition and strengthening the relationship between tertiary and community hospitals. PMID- 8433703 TI - Periventricular-intraventricular hemorrhage in the very low birth weight infant. AB - Although survival of very low birth weight infants has improved with advancements in technology and neonatal care, the risk of periventricular-intraventricular hemorrhage (PV-IVH) may be as high as 61 to 70 percent for this vulnerable population. Nursing can play an important role in reducing risk factors that contribute to PV-IVH, particularly during the first week of life, when a germinal matrix hemorrhage and its extension is most likely to occur. The pathophysiology of PV-IVH and a table of nursing interventions are presented to aid nurses in the assessment and planning of care for these tiny patients, who are at greatest risk for PV-IVH. PMID- 8433704 TI - Monoclonal antibodies to HIV-1 p24 core protein include pairs which exhibit synergistic binding. AB - Gamma and kappa chain cDNAs from four mouse monoclonal antibodies (mAbs) which bind three different sites on the core antigen (p24) of HIV-1 have been cloned and their V-region sequences determined. These mAbs are part of a larger group of seven anti-p24 mAbs analyzed in simultaneous competition assays with HIV-1 lysate as antigen and in protein blotting experiments using 10 carboxy-terminal truncations of a p24 fusion protein. One mAb, BB128, recognizes the p24 loop sequence EAAEWDRVHP and enhances the binding of two other mAbs (BI1777 and BI1279) when tested pairwise in simultaneous competition assays. The two monoclonals enhanced by BB128 recognize different antigenic sites on p24, with BI1777 binding to carboxy-terminal sequences and BI1279 to amino-terminal residues. In the pairwise assays, mAb BI1279 also acts as enhancing antibody for BI1777, as does mAb BB328, which recognizes residues in the central region of p24. Since aggregated p24 monomers form the HIV-1 capsid, p24 is a multivalent antigen in HIV-1 lysate. It seems likely, therefore, that synergistic binding of mAb pairs to p24 is effected by bivalent binding of the enhancing mAb stabilizing a conformation favorable for bivalent binding of the enhanced mAb. PMID- 8433705 TI - Interactions of cell-surface galactosyltransferase with immunoglobulins. AB - Detection of the activity of beta-1,4-galactosyltransferase (beta-1,4-GT) in suspensions of viable mouse hepatocytes, the human hepatoma cell line Hep G2, the human colonic adenocarcinoma cell line HT-29, the monocyte-like cell line U937, and human splenic B and T lymphocytes suggested the presence of beta-1,4-GT, in an enzymatically active form, on plasma membranes. The presence of beta-1,4-GT on cell surfaces was also indicated from the effect of trypsinization of live cells, which significantly reduced cell surface beta-1,4-GT activity, but did not affect the activity associated with cytoplasmic membranes. Furthermore, the presence of beta-1,4-GT on the cell surface was demonstrated by indirect immunofluorescence staining of cells with anti-beta-1,4-GT antibody. The detection of radioactivity in immunoglobulins (Ig) and their component chains after incubation with suspensions of intact cells in the presence of Mn2+ and UDP-[3H]-galactose, indicated that Ig molecules were galactosylated. In the absence of UDP-[3H] galactose, beta-1,4-GT on cell surfaces, or immobilized on Sepharose-4B, formed stable complexes with galactose acceptors, including Ig. The efficiency of binding decreased in the order: J chain > alpha chain > mu chain > polymeric IgA2 > monomeric/polymeric IgA1 > IgM > IgG. Thus, beta-1,4-GT could act as a cell surface receptor for Ig through a cation-dependent, lectin-like association of the beta-1,4-GT with the carbohydrate moieties of the Ig. This was confirmed by indirect surface immunofluorescence and radiolabeled ligand binding assays. The binding was inhibitable by EDTA, alpha-lactalbumin (in the presence of glucose), GlcNAc, or uridine 3',5'dialdehyde. At 37 degrees C, the apparent affinity constants and association rate constants of interaction between cell surface beta 1,4-GT on glutaraldehyde-fixed HT-29 and U937 cells and alpha 2 chain or monomeric IgA1 were in the range from 7.1 x 10(7) to 4.6 x 10(8) M-1 and from 1 x 10(5) to 3 x 10(6) M-1 s-1, respectively. The dissociation rate constants and half time of dissociation calculated from these data were in the range from 2.1 x 10(-2) to 5.0 x 10(-4) s-1 and from 33 to 1380 s, respectively. The number of alpha 2 or IgA1 molecules bound per HT-29 and U937 cell were in the range from 1.9 x 10(5) to 1.3 x 10(6). The binding of IgA by the cell surface beta-1,4-GT was not associated with internalization or the catabolic degradation of the ligand. PMID- 8433706 TI - Interactions of galactosyltransferase with serum and secretory immunoglobulins and their component chains. AB - Assay of the activity of beta-1,4-galactosyltransferase (beta-1,4-GT) revealed that in addition to serum, milk, colostrum, amniotic and cerebrospinal fluids and malignant effusions, this enzyme is present also in tears and saliva. Molecular sieve chromatography of human colostral whey and serum and subsequent assay of beta-1,4-GT activity have shown that beta-1,4-GT was present as a free enzyme (55 kDa) and associated with components of larger molar mass. The elution pattern did not change when the chromatography was carried out in a buffer devoid of, or enriched with, Mn2+, a cofactor of beta-1,4-GT activity. However, the activity associated with the large molar mass components was absent when the chromatography was carried out in the presence of a chelating agent (EDTA). Analyses of the eluted material by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE), and by immunodiffusion indicated that the major colostral component in beta-1,4-GT activity-containing fractions was secretory IgA (S-IgA); in addition, the beta-1,4-GT activity was detected in fractions that contained lactoferrin and alpha-lactalbumin. Interactions of beta 1,4-GT with S-IgA and lactoferrin in colostrum were also demonstrated by the detection of radioactivity in precipitin lines obtained by immunoelectrophoresis and autoradiography of the colostral whey after it had been incubated with UDP [3H]-galactose. Furthermore, radioactively labeled S-IgA and alpha-chain were detected when colostral whey incubated with UDP-[3H]-galactose was analyzed by SDS-PAGE under non-reducing and reducing conditions, respectively. In serum, the beta-1,4-GT-binding components identified in fractions after molecular-sieve chromatography were IgG, IgA, IgM and transferrin. The binding of beta-1,4-GT to immunoglobulins (Ig) was also demonstrated by assaying the beta-1,4-GT activity associated with Sepharose-4B-immobilized Ig of various isotypes and molecular forms, which were incubated with colostral beta-1,4-GT in the presence of Mn2+. Beta-1,4-GT measured by enzyme activity was bound to these Ig in order: polymeric IgA2 > monomeric IgA1 = polymeric IgA1 = secretory IgA = pentameric IgM > IgG. Immobilized component chains, namely alpha, mu and J chains, bound beta-1,4-GT more effectively than native Ig. Incubation of the IgA1 myeloma protein with crude human colostral galactosyltransferase in the presence of UDP[3H]-galactose and Mn2+ resulted in galactosylation of both N- and O-linked carbohydrate side chains.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8433707 TI - Serological and molecular characterization of mouse anti-idiotypic monoclonal antibodies elicited with the syngeneic anti-HLA-A2,28 monoclonal antibody CR11 351. AB - The molecular basis of the differential specificity of seven mouse anti-id mAb elicited with the syngeneic anti-HLA-A2,28 mAb CR11-351 was analyzed by comparing their specificity with their heavy and light chain variable region sequences. Of the six mAb recognizing idiotopes within the antigen combining site of mAb CR11 351, mAb T10-352, T10-440 and T10-505 recognize the same (or spatially close) idiotope(s) since they cross-inhibit each other in their binding to mAb CR11-351 and elicit syngeneic anti-anti-id antibodies with similar specificity. On the other hand, mAb T10-421, T10-649 and T10-938 appear to recognize spatially close but distinct idiotopes since they cross-inhibit each other, but elicit anti-anti id antibodies which inhibit only the binding of the respective immunizing anti-id mAb to mAb CR11-351. mAb T8-203 is the only anti-id mAb which recognizes an idiotope outside the antigen combining site of mAb CR11-351 since it does not inhibit the binding of the latter to target cells and binds to mAb CR11-351 coated B lymphoid cells. In addition, mAb T8-203 defines an idiotope which is shared by seven anti-HLA mAb, while the remaining six anti-id mAb recognize idiotopes which are not detectable on the panel of anti-HLA mAb. mAb T10-352, T10 440 and T10-505 are highly homologous in their VH and VL regions and in their V(D)J junctions suggesting that they may be clonally related. On the other hand, mAb T8-203, T10-649 and T10-938 share some degree of homology in their VH region as all of them use J558 VH genes but differ considerably in their VL regions. Finally, mAb T10-421 is the most unrelated mAb as it utilizes VH, D, JH, VK and JK gene segments different from those of all the other anti-id mAb. These findings indicate that in the HLA-A antigenic system defined by mAb CR11-351 the main mechanism underlying the differential target specificity of syngeneic anti id mAb is the combinatorial diversity together with the differential pairing of heavy and light chains. PMID- 8433708 TI - Mechanism of interferon-gamma down-regulation of the interleukin 4-induced CD23/Fc epsilon RII expression in human B cells: post-transcriptional modulation by interferon-gamma. AB - It has been reported that the interleukin 4 (IL-4) specific induction of cell surface CD23 (Fc epsilon RII) is down-regulated by interferon-gamma (IFN-gamma) in monocytes and B cells. However, the molecular level at which the inhibition occurs seems to vary depending on the cell types. In normal human B cells, IFN gamma inhibits the IL-4 induced de novo synthesis of CD23 at the level of gene expression. Analysis of inhibition kinetics suggested a rapid signal transmission by IFN-gamma. Yet the inhibitory action of IFN-gamma on CD23 mRNA accumulation appeared as a secondary response requiring a new protein synthesis. Through nuclear run-on transcription and mRNA stability studies, we further demonstrate that the IL-4 induced CD23 gene expression is down-regulated by IFN-gamma mainly at post-transcriptional levels by decreasing mRNA stability. PMID- 8433709 TI - High molecular weight non-immunoglobulin salivary agglutinins (NIA) bind C1Q globular heads and have the potential to activate the first complement component. AB - Non-Immunoglobulin Salivary Agglutinins (NIA) which directly bind to microbes [including HIV] were studied for their potential to activate the first complement component (C1). It was determined that NIA had the same specific activity as heat aggregated IgG in binding to C1q and in activating C1. In order to determine the region of C1q which bound to NIA, C1q globular heads and C1q stems (collagen-like regions) were prepared and separated via a Western blot procedure. NIA bound principally to the globular heads of C1q and weakly to the collagen-like stem region. NIA were also studied for their potential to activate native C1 in normal human serum. Heat-aggregated IgG and cardiolipin served as positive controls. It was observed that incubation of isolated NIA with fresh normal human serum resulted in the formation of sodium dodecyl sulfate (SDS)-irreversible complexes of activated C1r-C1 inhibitor and activated C1s-C1 inhibitor and in activated C1s mediated C4 conversion. This indicated that isolated NIA had the potential to directly and effectively mediate classical complement pathway activation. Preincubation of NIA with C1q, blocked NIA mediated C1r and C1s activation and C4 conversion. The concn of NIA required to activate C1r and C1s was similar to that of heat-aggregated human IgG. In kinetic ELISA, NIA or aggregated IgG (positive controls) were first immobilized on microtiter plates, blocked with gelatin then incubated with fresh human serum as a source of complement. Depositions of C4b, C3b and iC3b substantiated that the complement system was effectively activated by immobilized NIA. The optimal relative NaCl concn for C4b deposition was 0.11 M. While pre-incubation of NIA with C1q blocked the subsequent C1 fixing potential of NIA, pre-incubation of NIA with rgp160 [HIV-1] or fibronectin did not interfere with the potential of NIA to fix C1. PMID- 8433710 TI - The N-linked oligosaccharides of the Fc epsilon receptors of rat basophilic leukemia cells. AB - This study was undertaken to investigate the nature and microheterogeneity of the carbohydrate moiety of the Fc epsilon receptors of RBL-CA10 and RBL-CA10.7 cells. Treatment using the glycosylation processing inhibitors, castanospermine (CN), 1 deoxymannojirimycin (DMJ), and swainsonine (SW) resulted in a decrease of the relative molecular mass (M(r)) of both the alpha-chain of the high affinity receptor for IgE, Fc epsilon RI(alpha), and the low affinity receptor for IgE, Fc epsilon RL. Exposure to DMJ had the greatest effect on the M(r), while CN seemed to lead to a decreased cell surface expression of Fc epsilon RI. Both receptors are largely resistant to endoglycosidase H as their M(r) decreased only by approximately 2 kDa. These results suggest that both receptors are composed primarily of complex oligosaccharides with a single high mannose, N-glycosylated site. Both Fc epsilon receptors become endoglycosidase H sensitive if first exposed to DMJ which indicates that the carbohydrate composition is indeed altered by this processing inhibitor presumably by blocking the formation of complex structures. When the Fc epsilon receptors were reduced and hydrolyzed by N-glycanase, the M(r) values for Fc epsilon RI(alpha) and Fc epsilon RL decreased to approximately 28 and 34-38 kDa respectively. In the case of Fc epsilon RI(alpha), this implies the presence of only a small amount of O-linked oligosaccharides. PMID- 8433711 TI - Characterisation of a family of multi-copy genes encoding rhoptry protein homologues in Babesia bovis, Babesia ovis and Babesia canis. AB - A monoclonal antibody that had been raised against a protease-containing fraction of Babesia bovis, and shown to bind to a protein located in the rhoptries, was used to screen a B. bovis cDNA expression library. The sequence of the protein encoded by a positive clone was almost identical to the equivalent region of a previously described B. bovis 60-kDa rhoptry protein (Bv60). A tandem repeat of the gene encoding Bv60 was identified in all Australian isolates of B. bovis examined. Genes encoding homologous of Bv60 were cloned from Babesia ovis and Babesia canis. In B. ovis, 5 closely linked genes were identified. Four of these genes appeared to encode very similar proteins (Bo60.1-4). The protein (Bo60.5) encoded by the fifth B. ovis gene had 72% amino acid identity to Bo60.1-4 in the amino-terminal 306 amino acids, but no significant similarities in the carboxy terminal region. In B. canis one gene (Bc60.2) was sequenced and a second closely linked gene was identified. A further member of the family, p58, has also been described previously from Babesia bigemina. Tandemly repeated genes subject to extensive gene conversion appear to be a feature of this family of babesial rhoptry protein homologous. No proteins significantly related to any members of the gene family were identified in a search of translated DNA and protein sequence databases. Thus the function of this family of proteins remains a matter for speculation. PMID- 8433712 TI - Cloning of the gene encoding a Schistosoma mansoni antigen homologous to human Ro/SS-A autoantigen. AB - A cDNA library was constructed from the mRNA of adult worms of Schistomsoma mansoni in the expression vector lambda gt11 and screened with a rabbit antiserum raised against a 60-65-kDa electroeluted adult worm fraction. Two overlapping clones were selected and a partial nucleotide sequence was deduced (1172 bp). The full-length sequence was obtained by the amplification of the 5' end of first strand cDNA using PCR. The overall mRNA size was 1335 nt including a 25 nt 5' non coding region and a 131 nt untranslated region with the poly(A) tail. The predicted amino acid sequence of 393 aa (45 kDa) has 52% identity with the human Ro/SS-A autoantigen, which is considered to be the human calreticulin. As for the human Ro/SS-A, the protein encoded by the cDNA described here contains a hydrophobic leader sequence and a carboxyl terminal sequence, HDEL consensus signal sequence for retention in the ER. An antiserum raised against the fusion protein of one clone recognized a 58-kDa antigen in homogenates of cercariae and of adult worms. The expression of the protein in the pGEX-2T fusion system allowed us to show the presence of specific antibodies in S. mansoni infected patients' sera and in the sera of patients with systemic lupus erythematosus, reflecting a cross-immunoreactivity between the S. mansoni protein and the human calreticulin autoantigen. PMID- 8433713 TI - Identification, isolation, and characterization of naturally-occurring Trypanosoma cruzi variants. AB - Naturally occurring DNA variants of the single-cell-derived Y-02 stock of Trypanosoma cruzi were discovered during a routine assay of the stock. Three DNA variant types were isolated. One type was indistinguishable from the parental Y 02 stock on the basis of total DNA cell-1. The other two types contained approximately 30% and 70% more DNA cell-1 than the parental Y-02 stock. Both the nucleus and kinetoplast were involved in the DNA content differences. The increase in DNA cell-1 was not G-C- or A-T-specific and was unrelated to the developmental stage of the parasite. Epimastigote population doubling times, isoenzymes, and schizodeme analyses could not differentiate the variant stocks. However, marked karyotype polymorphisms were observed by pulse-field gel electrophoresis, and restriction-fragment-length-polymorphisms were detected in hybridizations of some endonuclease-restricted samples to the spliced leader probe. We postulate that the Y-02 variants are genetic homologs. The ability to form viable hybrids or aneuploids provides T. cruzi with a mechanism to survive environmental stress, promote intra-specific heterogeneity and generate the diversity observed in the presentation and course of Chagas' disease. PMID- 8433714 TI - Identification of a tRNA-like molecule that copurifies with the 7SL RNA of Trypanosoma brucei. AB - During the purification of Trypanosoma brucei 7SL RNA, we detected a small RNA, 76 nucleotide-long (sRNA-76), that copurified with the 7SL RNP through several different separation steps. In this study, a partial RNA sequence of sRNA-76 was obtained and a complementary oligonucleotide to the RNA sequence was used to clone the corresponding gene. sRNA-76 is very similar to a tRNA molecule and is encoded by a single copy gene. The gene is located next to a tRNA(Val) which has 75.3% homology to T. brucei tRNA(Val) that exists in a different chromosomal locus. The highest homology of sRNA-76 is to mouse and rat tRNA(Asp) (69%), to mouse tRNA(Gly) (68.1%) and to yeast suppressor tRNA(Gly) (69.5%). However, sRNA 76 is neither a tRNA(Asp) nor a tRNA(Gly), since it has a Leu anticodon. In addition, sRNA-76 deviates from the canonical tRNA structure in 3 positions. A potential for base pairing between sRNA-76 and 7SL RNA was found in the 100 nt region of 7SL RNA, which is a highly conserved region in all 7SL RNAs. PMID- 8433715 TI - Control of G1 to S cell cycle progression of Trypanosoma brucei S427cl1 organisms under axenic conditions. AB - Trypanosoma brucei S427cl1 organisms made 6 divisions in modified minimal essential medium (BMEM) supplemented with fetal bovine serum (FBS)-low or high density lipoprotein (LDL, HDL) and fatty acid-free bovine serum albumin (FAF BSA). Omission of lipoproteins or FAF-BSA from the medium caused the parasites to accumulate in G1 of the cell cycle and to lose the ability to replicate at 37 degrees C. Proteinase K-treated LDL or HDL, which did not have detectable apolipoprotein, supported the G1 to S cell cycle transition of T. brucei S427cl1 organisms in BMEM supplemented with FAF-BSA. Addition of C6:0, C7:0 or fatty C8:0 fatty acid (1 mol fatty acid mol-1 FAF-BSA in the incubation mixture) to serum free medium supplemented with LDL or HDL and FAF-BSA prevented T. brucei S427cl1 organisms from progressing through G1 into S of the cell cycle. T. brucei S427cl1 organisms became stumpy-like forms during plateau phase growth under axenic conditions. Stumpy-like T. brucei S427cl1 organisms were mainly in G1 of the cell cycle, expressed raised levels of NAD diaphorase activity, were unable to replicate at 37 degrees C, but were able to differentiate to replicating procyclic organisms. Medium collected from plateau phase cultures of T. brucei S427cl1 did not support the G1 to S cell cycle transition of exponentially growing T. brucei organisms. The capacity of plateau phase medium to support G1 to S transition of T. brucei S427cl1 organisms was restored by addition of FAF BSA and its capacity to support 4 cycles of replication of the parasites was restored by addition of FAF-BSA and LDL or HDL. PMID- 8433716 TI - Identification, purification and separation of different isozymes of NADP specific malic enzyme from Tritrichomonas foetus. AB - Tritrichomonas foetus was found to contain NADP-specific malic enzyme. The activity was present in the cytosolic fraction and was about 5-fold higher in extracts of a metronidazole-resistant strain (KV1-1MR-100) than of the parent strain (KVc1). Electrophoresis under non-denaturing conditions and activity staining indicated the existence of 3 isozymes termed I, II and III in order of increasing electrophoretic mobility. Isozymes I and II were much less active than isozyme III in the parent strain, whereas all three isozymes had comparable activities in the resistant strain. NADP-malic enzymes were purified from the cytosolic fraction of the resistant strain to apparent homogeneity and were identified by SDS-PAGE as polypeptides of 41.5 kDa (I), 40.5 kDa (III) and as a mixture of both in equal amounts (II). The molecular mass of the three holoenzymes was about 180 kDa, as determined by gel-filtration on Sephacryl S-300 HR, indicating a tetrameric structure. Isozyme III was also purified from parent strain and shown to consist of the 40.5-kDa polypeptide. Km values for malate were 0.31, 0.65 and 1.35 mM for isozyme I, II and III, respectively. From these results we conclude that T. foetus+, which is required for the formation of ethanol by alcohol dehydrogenase, an NADP-specific enzyme in this species. This is particularly important for the resistant strain, in which ethanol is the major end-product of glucose metabolism. PMID- 8433717 TI - RNA virus-like particles in pathogenic plant trypanosomatids. AB - A double-stranded RNA (ds RNA) with an approximate size of 4.7 kb was found in 6 Phytomonas isolates specifically associated with plant pathogenicity in coconut trees ("Hartrot" disease) and oil palm ("Marchitez sorpressiva" disease). This ds RNA was not detected in 10 non-pathogenic Phytomonas isolates from different lactiferous plants or in the insect trypanosomatids Crithidia and Herpetomonas. Analysis by electron microscopy of a sucrose gradient fraction containing this ds RNA revealed virus-like particles. PMID- 8433718 TI - Biogenesis of rhoptry organelles in Plasmodium falciparum. AB - Biogenesis of the rhoptry organelle of Plasmodium falciparum was studied by examining the synthesis and assembly of rhoptry proteins at different stages of intraerythrocytic development. Rhoptry proteins examined in this study were those of the high molecular weight complex of 140/130/110 kDa and referred to as Rhop H1,2,3 and the low molecular weight complex of 80 and 42 kDa referred to as Rhop L1,2. Co-ordinate, stage-specific expression of three proteins, Rhop-H3, Rhop-L1 and Rhop-L2, was observed; maximum levels of mRNA at the 8 nucleus stage correlated with the onset of protein synthesis. In contrast, mRNA levels for DNA polymerase-alpha, a marker for DNA replication during schizogony, was maximum just prior to the onset of the first nuclear division, indicating that rhoptry biogenesis is not co-ordinate with nuclear division. The assembly of newly synthesized rhoptry proteins was followed by subcellular fractionation of schizonts at different stages of development. At the four-nucleus stage a vesicle could be isolated by sucrose gradient fractionation which had a peak density of 1.12 g ml-1 and contained only Rhop-H2 and Rhop-H3 proteins. This vesicle could represent an intermediate or pre-rhoptry compartment. At the 8-nucleus stage, the Rhop-L1 protein was also detected in a vesicle of low density. At the 16-nucleus stage, the proteins were present in vesicles having a significantly greater density in sucrose, 1.16 g ml-1, similar to that of the mature organelle. The study suggested that the rhoptry proteins first accumulate in a low density vesicle and that assembly into this compartment is staggered. Immunoelectronmicroscopy studies indicated that the Rhop-H3 protein is first present in small granular compartments that becomes more electron dense and enlarges due to the stage-dependent incorporation of proteins. PMID- 8433719 TI - Lipophosphoglycan-like glycoconjugate of Tritrichomonas foetus and Trichomonas vaginalis. AB - Lipophosphoglycan-like glycoconjugates were isolated, purified and partially characterized from Tritrichomonas foetus and Trichomonas vaginalis. Cell surface radiolabeling of both trichomonads by the galactose oxidase/NaB[3H]4 technique indicated that the glycoconjugate was located on the cell surface of the parasites. The glycoconjugates were extracted from the delipidated residue fraction with the solvent, water/ethanol/diethylether/pyridine/NH4OH (15:15:5:1:0.017) and were purified to homogeneity by Sepharose CL-4B followed by octyl-Sepharose chromatography and methanol precipitation. The glycoconjugates migrated as broad bands upon SDS-PAGE. The T. foetus glycoconjugate contained large amounts of fucose along with some mannose, galactose, glucosamine and glucose and trace amounts of galactosamine and inositol. The T. vaginalis glycoconjugate appeared to contain large amounts of glucosamine and galactose along with some glucose, mannose and traces of galactosamine and inositol. The surface-labeled glycoconjugates from both parasites was found to be deaminated with nitrous acid and susceptible to phosphatidylinositol-specific phospholipase C, indicating the presence of a phospholipid anchor. Furthermore, these glycoconjugate were found to contain phosphate and were labile to hydrolysis by mild acid, strongly suggesting that the intact molecule is related to Leishmania lipophosphoglycans (LPG). The most striking and the unique features of these glycoconjugate molecules are the presence of large amounts of fucose in T. foetus and glucosamine in T. vaginalis along with the presence of galactosamine in both parasites. These results indicate that these glycoconjugates are new types of LPG like molecules expressed on the trichomonad cell surface and are structurally distinct from Leishmania LPG. PMID- 8433720 TI - Insertion of the promoter for a variant surface glycoprotein gene expression site in an RNA polymerase II transcription unit of procyclic Trypanosoma brucei. AB - The variant-specific surface glycoprotein (VSG) genes of Trypanosoma brucei are invariably expressed near the ends of chromosomes (telomeres). We have targeted a VSG gene expression site (ES) promoter driving a selectable marker gene (neomycin phosphotransferase) into a chromosome-internal transcription unit, the tubulin gene array of procyclic trypanosomes. To avoid read through transcription of the marker gene from the tubulin promoter, we targeted the ES promoter in inverse orientation relative to tubulin gene transcription. The only correctly targeted transformant obtained contained the marker gene close to the border of the tubulin gene array, and expression of this gene was relatively low. Possible reasons for the low targeting efficiency and expression level are discussed. PMID- 8433721 TI - A ribosomal S12-like gene of Trypanosoma brucei. PMID- 8433722 TI - A cDNA encoding repeating units of the ABA-1 allergen of Ascaris. PMID- 8433723 TI - Plasmodium chabaudi-parasitized erythrocytes: phosphatidylcholine species of parasites and host cell membranes. PMID- 8433724 TI - The filarial antigens Av33/Ov33-3 show striking similarities to the major pepsin inhibitor from Ascaris suum. PMID- 8433725 TI - A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. The Primary Angioplasty in Myocardial Infarction Study Group. AB - BACKGROUND: The success of thrombolytic therapy for acute myocardial infarction is limited by bleeding complications, the impossibility of reperfusing all occluded coronary arteries, recurrent myocardial ischemia, and the relatively small number of patients who are appropriate candidates for this therapy. We hypothesized that these problems could be overcome by the use of immediate percutaneous transluminal coronary angioplasty (PTCA), without previous thrombolytic therapy. METHODS: At 12 clinical centers, 395 patients who presented within 12 hours of the onset of myocardial infarction were treated with intravenous heparin and aspirin and then randomly assigned to undergo immediate PTCA (without previous thrombolytic therapy, 195 patients) or to receive intravenous tissue plasminogen activator (t-PA, 200 patients) followed by conservative care. Radionuclide ventriculography was performed to assess ventricular function within 24 hours and at six weeks. RESULTS: Among the patients randomly assigned to PTCA, 90 percent underwent the procedure; the success rate was 97 percent, and no patient required emergency coronary-artery bypass surgery. The in-hospital mortality rates in the t-PA and PTCA groups were 6.5 and 2.6 percent, respectively (P = 0.06). In a post hoc analysis, the mortality rates in the subgroups classified as "not low risk" were 10.4 and 2.0 percent, respectively (P = 0.01). Reinfarction or death in the hospital occurred in 12.0 percent of the patients treated with t-PA and 5.1 percent of those treated with PTCA (P = 0.02). Intracranial bleeding occurred more frequently among patients who received t-PA than among those who underwent PTCA (2.0 vs. 0 percent, P = 0.05). The mean (+/- SD) ejection fractions at rest (53 +/- 13 vs. 53 +/- 13 percent) and during exercise (56 +/- 13 vs. 56 +/- 14 percent) were similar in the t-PA and PTCA groups at six weeks. By six months, reinfarction or death had occurred in 32 patients who received t-PA (16.8 percent) and 16 treated with PTCA (8.5 percent, P = 0.02). CONCLUSIONS: As compared with t-PA therapy for acute myocardial infarction, immediate PTCA reduced the combined occurrence of nonfatal reinfarction or death, was associated with a lower rate of intracranial hemorrhage, and resulted in similar left ventricular systolic function. PMID- 8433726 TI - A comparison of immediate coronary angioplasty with intravenous streptokinase in acute myocardial infarction. AB - BACKGROUND: Despite the widespread use of intravenous thrombolytic therapy and of immediate percutaneous transluminal coronary angioplasty for the treatment of acute myocardial infarction, randomized comparisons of the two approaches to reperfusion are lacking. We report the results of a prospective, randomized trial comparing immediate coronary angioplasty (without previous thrombolytic therapy) with intravenous streptokinase treatment. METHODS: A total of 142 patients with acute myocardial infarction were randomly assigned to receive one of the two treatments. The left ventricular ejection fraction was measured by radionuclide scanning before hospital discharge. Quantitative coronary angiography was performed to assess the degree of residual stenosis in the infarct-related arteries. RESULTS: A total of 72 patients were assigned to receive streptokinase and 70 patients to undergo immediate angioplasty. Angioplasty was technically successful in 64 of the 65 patients who underwent the procedure. Infarction recurred in nine patients assigned to receive streptokinase, but in none of those assigned to receive angioplasty (P = 0.003). Fourteen patients in the streptokinase group had unstable angina after their infarction, but only four in the angioplasty group (P = 0.02). The mean (+/- SD) left ventricular ejection fraction as measured before discharge was 45 +/- 12 percent in the streptokinase group and 51 +/- 11 percent in the angioplasty group (P = 0.004). The infarct related artery was patent in 68 percent of the patients in the streptokinase group and 91 percent of those in the angioplasty group (P = 0.001). Quantitative coronary angiography revealed stenosis of 36 +/- 20 percent of the luminal diameter in the angioplasty group, as compared with 76 +/- 19 percent in the streptokinase group (P < 0.001). CONCLUSIONS: Immediate angioplasty after acute myocardial infarction was associated with a higher rate of patency of the infarct related artery, a less severe residual stenotic lesion, better left ventricular function, and less recurrent myocardial ischemia and infarction than was intravenous streptokinase. PMID- 8433727 TI - Immediate angioplasty compared with the administration of a thrombolytic agent followed by conservative treatment for myocardial infarction. The Mayo Coronary Care Unit and Catheterization Laboratory Groups. AB - BACKGROUND: Immediate angioplasty and the administration of a thrombolytic agent followed by conservative treatment are two approaches to the management of acute myocardial infarction, but these methods have not been compared prospectively. METHODS: We enrolled 108 patients with acute myocardial infarction in a randomized trial designed to test the hypothesis that immediate angioplasty (without previous thrombolytic therapy) may result in greater myocardial salvage than the administration of a thrombolytic agent followed by conservative treatment. The primary end point was the change in the size of the perfusion defect as assessed at admission and discharge by tomographic imaging with technetium-99m sestamibi, a myocardial perfusion agent that can measure myocardium at risk and final infarct size. RESULTS: End-point data were available for 56 patients randomly assigned to receive tissue plasminogen activator (mean [+/- SD] time to start of infusion, 232 +/- 174 minutes after the onset of chest pain) and 47 patients randomly assigned to receive angioplasty (first balloon inflation at 277 +/- 144 minutes). In the case of anterior infarction, myocardial salvage as assessed by imaging with technetium-99m sestamibi was 27 +/- 21 percent of the left ventricle for 22 patients in the thrombolysis group, as compared with 31 +/- 21 percent for 15 patients in the angioplasty group. For infarcts in all other locations, myocardial salvage was 7 +/- 13 percent for 34 patients in the thrombolysis group and 5 +/- 10 percent for 32 patients in the angioplasty group. After adjustment for infarct location, the difference in mean salvage between groups was 0 (P = 0.98), with a 95 percent confidence interval of +/- 6 percent of the left ventricle. CONCLUSIONS: In patients with acute myocardial infarction, immediate angioplasty does not appear to result in greater myocardial salvage than the administration of a thrombolytic agent followed by conservative treatment, although a small difference between these two therapeutic approaches cannot be excluded. PMID- 8433728 TI - Diagnostic value of blood sampling in fetuses with growth retardation. AB - BACKGROUND: Fetuses with intrauterine growth retardation are delivered if they have evidence of distress, as manifested by abnormalities in the fetal heart rate and umbilical-artery blood flow. We studied whether umbilical-blood sampling might provide further information useful for management. METHODS: We measured hemoglobin and lactate concentrations, oxygen content, pH, blood gas levels, and base deficit in umbilical-vein blood and correlated these measurements with the heart rate and umbilical-artery wave forms recorded by Doppler velocimetry in 56 fetuses with growth retardation. Twenty-one fetuses had normal heart rates and normal results of velocimetry, 24 had normal heart rates and abnormal results of velocimetry (indicative of decreased diastolic flow), and 11 had abnormal heart rates and abnormal results of velocimetry. RESULTS: None of the 21 fetuses with normal heart rates and velocimetry had hypoxia or acidemia. Of the 24 fetuses with normal heart rates and abnormal velocimetry, 4 (17 percent) had moderate lactic acidosis, 1 (4 percent) had a low pH value, and 3 (12 percent) had hypoxia. Of the 11 fetuses with abnormal heart rates and velocimetry, 7 (64 percent) had lactic acidosis, low blood oxygen content, and low pH values. The absence of end-diastolic flow increased the risk of hypoxia and acidemia. The proportion of fetuses with elevated hemoglobin concentrations was similar among the three groups. CONCLUSIONS: Assessment of fetal oxygenation and acid-base balance is not indicated in fetuses with growth retardation if their heart rates and the results of velocimetry are normal. If the results of velocimetry are abnormal, fetal-blood sampling can distinguish fetuses that have growth retardation alone from those that also have hypoxia and acidosis, and thus may aid in determining the optimal time of delivery. PMID- 8433729 TI - Familial hyperglycemia due to mutations in glucokinase. Definition of a subtype of diabetes mellitus. AB - BACKGROUND AND METHODS: Non-insulin-dependent diabetes mellitus (NIDDM) is a genetically heterogeneous disorder. Maturity-onset diabetes of the young, a form of NIDDM with an early age of onset and autosomal dominant inheritance, can result from mutations in glucokinase, a key enzyme of glucose metabolism in beta cells and the liver. We studied 32 French families with maturity-onset diabetes of the young as well as 21 families with late-onset NIDDM to determine the frequency and clinical features of mutations of glucokinase. Fasting plasma glucose concentrations and oral glucose-tolerance tests were used to determine metabolic status. DNA was isolated from lymphocytes, and DNA polymorphisms in the glucokinase gene were tested for linkage with diabetes. Individual exons of the glucokinase gene from one affected member in each family were amplified by the polymerase chain reaction and screened for mutations by analysis of the conformation-dependent polymorphisms of single-stranded DNA and by DNA sequencing. RESULTS: We found substantial evidence of linkage between the glucokinase locus and maturity-onset diabetes of the young but not between this locus and late-onset NIDDM: Sixteen mutations were identified in 18 of the 32 families with maturity-onset diabetes of the young, but none were found in families with late-onset NIDDM: They included 10 mutations that resulted in an amino acid substitution, 3 that resulted in the synthesis of a truncated protein, and 3 that affected RNA processing. The affected subjects with glucokinase mutations usually had mild hyperglycemia that began during childhood, whereas in subjects with maturity-onset diabetes of the young not due to glucokinase mutations, hyperglycemia usually appeared after puberty. CONCLUSIONS: Mutations in glucokinase are the primary cause of hyperglycemia in a substantial fraction of French patients with maturity-onset diabetes of the young and result in a relatively mild form of NIDDM that can be diagnosed in childhood. PMID- 8433730 TI - Brief report: trimethoprim-induced hyperkalemia in a patient with AIDS. PMID- 8433731 TI - Magnetic resonance imaging (1). PMID- 8433732 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 10-1993. A 67-year-old man with mitral regurgitation and an abrupt onset of ataxia and fever. PMID- 8433733 TI - Immediate angioplasty for acute myocardial infarction. PMID- 8433734 TI - Cordocentesis and fetuses that are small for gestational age. PMID- 8433735 TI - A defective beta-cell glucose sensor as a cause of diabetes. PMID- 8433736 TI - The breast-implant controversy. PMID- 8433737 TI - The breast-implant controversy. PMID- 8433738 TI - The breast-implant controversy. PMID- 8433739 TI - The breast-implant controversy. PMID- 8433740 TI - The breast-implant controversy. PMID- 8433741 TI - High-dose epinephrine in cardiopulmonary resuscitation. PMID- 8433742 TI - Telling the diagnosis of Alzheimer's disease. PMID- 8433743 TI - Some more costs of managed care. PMID- 8433744 TI - Compensating egg donors: equal pay for equal time? PMID- 8433746 TI - The ministry of caring, Part 3. PMID- 8433745 TI - Taking shape. Environmental art in health care. PMID- 8433747 TI - Drama in the medical school classroom. The actor as patient. PMID- 8433748 TI - The role of the arts in physician stress management. PMID- 8433749 TI - The risks of HIV infection. PMID- 8433750 TI - Upper respiratory disease in asthmatics. PMID- 8433751 TI - Two support "up front" fees. PMID- 8433752 TI - The role of somatic education in dance medicine and rehabilitation. PMID- 8433753 TI - Medicine in the vocal arts. PMID- 8433754 TI - Prostate cancer. PMID- 8433755 TI - Music therapy in medical settings. PMID- 8433756 TI - Medicine and literature. PMID- 8433757 TI - [From the frying pan into the fire]. PMID- 8433758 TI - [Surgical correction in urinary incontinence and (or) symptoms of prolapse]. PMID- 8433759 TI - [The mirror and the boomerang; observations on the effects of aid to developing countries]. PMID- 8433760 TI - [Computerized tomography following arthrography in instability of the shoulder joint]. PMID- 8433761 TI - [Results and complications of vaginal correction of vaginal and uterine prolapse with or without urinary incontinence; a prospective study]. AB - Between 1985 and 1987, 191 consecutive patients with a genital prolapse combined in 50% of the cases with urinary incontinence, underwent a vaginal repair with or without hysterectomy in the Ikazia hospital, Rotterdam. In a prospective study design, results and complications were assessed 4 and 12 months after the procedure. Mortality was 1%, morbidity was low; bladder or bowel injury did not occur. Vaginal prolapse recurred after 4 and 12 months in 4 and 6% of the patients, respectively. Of patients with involuntary loss of urine 31% still complained of incontinence 4 months after the operation; after one year this percentage was 49. Dyspareunia was a frequent complaint (41%), probably as a result of the posterior vaginal repair which was performed in all patients. We conclude that vaginal repair, with or without hysterectomy, allows successful treatment of genital prolapse, but is less satisfactory for the treatment of urinary incontinence, and a frequent cause of dyspareunia. PMID- 8433762 TI - [Consensus diagnosis pulmonary embolism]. AB - Pulmonary embolism is a frequent occurrence and requires adequate diagnosis and treatment to avoid unnecessary mortality and complications. However, until recently, the optimal diagnostic management was not determined. This prompted the organisation of a consensus meeting. The advised diagnostic strategy was derived from available data in the literature, a cost-effectiveness analysis, and the discussions which took place at the meeting. The preferred diagnostic strategy consists of a combination of perfusion-ventilation lung scintigraphy, ultrasonography of the legs, and finally pulmonary angiography. Perfusion scintigraphy is performed first. If a normal perfusion is seen further anticoagulant therapy may be withheld. Ventilation scintigraphy is performed if a segmental or larger perfusion defect is found. If a normal ventilation scan is obtained (mismatch) the diagnosis of pulmonary embolism is sufficiently certain to warrant institution of long-term anticoagulant therapy. In all other lung scan findings (non-conclusive or non-diagnostic) the meeting advised to perform ultrasonography of the legs. If deep venous thrombosis is detected the patient requires long-term anticoagulant therapy. If a normal ultrasound result is found, pulmonary angiography is required as the final test in the diagnostic strategy. PMID- 8433763 TI - [Risk of hemorrhage with the use of fluoxetine (Prozac) or fluvoxamine (Fevarin)]. AB - Fluoxetine (Prozac) and fluvoxamine (Fevarin) are nontricyclic serotonin (5 hydroxytryptamine) reuptake inhibitors prescribed for the treatment of depression. Since these drugs block serotonin reuptake in platelets also, they might under certain conditions lead to clinically significant platelet dysfunction. Four patients are described who developed bleeding during treatment with either fluoxetine or fluvoxamine. PMID- 8433764 TI - [Anniversary Save the Children]. PMID- 8433765 TI - [Evaluation of screening for cervix carcinoma]. PMID- 8433766 TI - [Evaluation of screening for cervix carcinoma]. PMID- 8433767 TI - [Evaluation of screening for cervix carcinoma]. PMID- 8433768 TI - [Are long-term results of venous aortocoronary bypass surgery really that poor? A 13-year prospective study in 428 patients]. PMID- 8433769 TI - [Long-lasting abdominal symptoms and ascites: remember also tuberculous peritonitis!]. PMID- 8433770 TI - [The value of vaccination against abdominal typhus using current vaccines is still controversial]. PMID- 8433771 TI - [Decompression sickness]. PMID- 8433772 TI - [Current viewpoints and hypotheses concerning in vivo blood coagulation]. PMID- 8433773 TI - [Indications for magnesium determination]. PMID- 8433774 TI - [Abdominal typhus and paratyphoid fever in 2 academic hospitals: 1984-1990]. AB - A diagnosis of blood culture-positive typhoid (TF; n = 39) or paratyphoid (PTF; n = 17) fever was made in 56 patients admitted to two Dutch university hospitals in the period 1984-1990. The group of TF patients constituted 9% of the reported national total during those years. A retrospective analysis of available clinical, laboratory and epidemiological data was carried out. Without exception, infections were contracted during travel abroad, especially to India and Indonesia. The clinical features and the response to antimicrobial treatment of TF and PTF proved essentially the same. Fever, headache and anorexia were important symptoms; rose spots and splenomegaly were found in 18/38 and 10/39 with S. typhi respectively. Most patients had a normal white blood cell count; less than half of the patients had thrombocytopenia. A positive Widal-test was found in 15/24 patients with S. typhi. 18/39 patients with S. typhi had been vaccinated; 10 did not know. Amoxycillin was the preferred antimicrobial agent in 69% of cases. Median defervescence time was 5 days in TF and 4 days in PTF. Relapse occurred in 3 TF cases. The recurrence rate after amoxycillin treatment was 7.6%. Profuse intestinal bleeding (1x), septic shock (1x) and cholangitis plus ARDS (1x) were major complications, seen in TF patients only. All patients recovered fully. None of the isolated strains of S. typhi or S. paratyphi proved multiresistant. Surveillance data from the Dutch National Institute of Public Health and Environmental Protection suggest that multidrug-resistance of S. typhi is increasing, especially in strains imported from countries such as India and Pakistan.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433775 TI - [Thyroid metastases as cause of thyroid swelling]. AB - In the period 1983-1991 16 patients with metastases to the thyroid gland were selected with the aim to compare the treatment results with those reported in literature and eventually arrive at a recommendation on treatment. There were 11 women and 5 men with a mean age of 62 years at diagnosis. The type of the primary tumour varied widely without clear predominance of any histology. The interval between the diagnosis of the primary tumour and the appearance of the thyroid metastasis varied from 0 to 9 years. Three patients were treated with chemotherapy, 3 with radiotherapy, 6 by surgery, 2 with a combination of surgery and postoperative radiotherapy and 2 patients were not treated at all. The median overall survival after treatment was 9 months. All patients eventually showed evidence of disease somewhere in their body. The local control until death or the last follow up visit was complete in case of surgery or a combination of surgery and radiotherapy. Chemotherapy resulted in 2 partial remissions and 1 stable disease. If there is fast systemic progression of disease with evident metastasis elsewhere or a short disease-free period an expectant policy is advocated. In case of (threatening) airway obstruction, a solitary metastasis or a long disease free period individualised treatment is indicated with the aim of lengthening the disease-free period. PMID- 8433776 TI - [Underreporting of first-week mortality in premature childbirth in the National Obstetrics Register]. AB - The reliability of the perinatal mortality as recorded in the Perinatal Database of the Netherlands (LVR), was studied over 1983. For this year is was possible to make a comparison between preterm infants in the LVR and the same infants recorded by paediatricians in the database of the Project on Preterm and Small for Gestational Age Infants in the Netherlands 1983 (POPS). The comparison between the recorded mortality of the same infants in these two anonymous databases was realised by a simple matching procedure. For the premature infants a 30% lower first week mortality was found in the LVR than in the POPS-group, which means that 10% of the total perinatal mortality (stillbirths and first-week deaths together) has not been registered in the LVR for this group, due to lack of adaptation of data after later deaths. The mortality in the LVR should be interpreted with caution while it is not yet possible to match the obstetric data to the data of the National Neonatology Registration. PMID- 8433777 TI - [Acute psychosis in a patient with a combination of sickle cell disease and hemoglobin-C disease]. AB - A 35-year-old negroid patient, known to have sickle cell-haemoglobin C disease, after heavy exercise developed an acute thrombotic crisis localised mainly in the brain. The clinical manifestations were those of an acute psychosis with severe confusion, aggressiveness, unco-operative behaviour and incontinence for faeces and urine. With adequate therapy he recovered after a few days. This so-called cerebral sickle cell crisis, confirmed by multiple small encephalomalacia lesions on the MRI which are typical of this disease, is a rare complication and difficult to diagnose. PMID- 8433778 TI - [Number of admissions for Reiter's disease (ICD-9-code 099.3) in Dutch hospitals in 1981-1987]. AB - The number of hospitalisations of male patients for Reiter's syndrome in the Netherlands declined over the period 1981 to 1987 by almost 40%. This decline is probably connected with a change in sexual behaviour, associated with the fear of AIDS. The number of admissions of female patients is considerably smaller than that of male patients, possibly due to underdiagnosis of the disease. PMID- 8433779 TI - [Risk of an unwanted pregnancy following a single unprotected coitus; observations concerning the current hormonal postcoital contraceptive methods]. PMID- 8433780 TI - [Risk of an unwanted pregnancy after a single unprotected coitus; observations on the current hormonal postcoital contraceptive methods]. PMID- 8433781 TI - [Risk of an unwanted pregnancy following a single unprotected coitus; observations concerning the current hormonal postcoital contraceptive methods]. PMID- 8433782 TI - Prenatal brain atrophy due to a giant vein of Galen malformation. AB - We report a full-term newborn girl with a giant vein of Galen malformation and extreme cerebral atrophy of prenatal origin. She presented on the 3rd day of life with intractable congestive heart failure. The diagnosis of the vascular malformation was confirmed by ultrasound and magnetic resonance imaging. PMID- 8433783 TI - CT demonstration of intracranial haemorrhage in term newborn following vacuum extractor delivery. AB - Ten term newborns underwent CT of the brain 12-24 h following vacuum extractor delivery. Haemorrhage in the area of the tentorium was demonstrated in all of them, with similar findings in all cases. CT 1 week later demonstrated reabsorption of the blood without demonstrating any other brain pathology. Clinical and CT examination a year after delivery did not reveal any abnormality. The haemorrhage appears to be a benign condition. PMID- 8433784 TI - Morphological studies of the corpus callosum by MRI in children with malformative syndromes. AB - A morphological analysis of the corpus callosum has been carried out in an MRI study of 34 children with malformative syndromes and 35 normal children. We used a new morphometric method based on measurement of five specific angles. Values outside the range of normality have been found in patients with malformations of the skull, including turricephaly, acrocephaly and frontonasal dysplasia. The results have confirmed the reliability of this method for study of the conformation of the corpus callosum and of its topographical relations with the other cerebral structures. PMID- 8433785 TI - Posterior cranial fossa dimensions in the Chiari I malformation: relation to pathogenesis and clinical presentation. AB - Skull dimensions were measured on lateral skull radiographs in 33 adult patients with MRI-verified Chiari I malformations and in 40 controls. The posterior cranial fossa was significantly smaller and shallower in patients than in controls. In the patients, there was a positive correlation between posterior fossa size and the degree of the cerebellar ectopia, which might indicate that a posterior cranial fossa which was originally too small had been expanded by the herniation of hindbrain structures at an early stage. Pyramidal signs and cerebellar symptoms and signs, which may be due to compression of neural structures, were associated with a large degree of ectopia and a relatively large posterior cranial fossa. Syringomyelia and headache, which may be due to the valve action of the herniated cerebellar tissue, were not associated with a particularly large posterior fossa or herniation. No special clinical presentation was associated with a very small posterior cranial fossa, which may indicate that a small posterior cranial fossa per se has little or no clinical significance, although it may be the primary developmental anomaly. PMID- 8433786 TI - Age distribution and iron dependency of the T2 relaxation time in the globus pallidus and putamen. AB - Heavily T2-weighted spin echo sequences of the brain show age-dependent low signal intensity in many extrapyramidal nuclei. Although it has been suggested that this low intensity results from non-haem iron, the specific influence of non haem iron on the T2 relaxation time has not been quantified and remains controversial. The T2 relaxation times of the globus pallidus and putamen were measured from MRI at 1.5T in 27 healthy patients, by using a mathematical model. They were then plotted as a function of age and compared to the curve of age dependent iron concentration determined post mortem. The curves of T2 relaxation time in the basal ganglia are congruent with published curves of iron concentration, indicating a high probability that the changes in T2 relaxation times and the low signal in the basal ganglia result from the local, age dependent iron deposition. Individual measurements of T2 relaxation time show less variation before than after 45 years of age, indicating the influence of a second, more individual factor. PMID- 8433787 TI - Periventricular hyperintensity on magnetic resonance imaging correlated with brain ageing and atrophy. AB - Fifty-two patients with cerebrovascular risk factors without neurological abnormalities were reviewed with respect to periventricular hyperintensity (PVH) on T2-weighted magnetic resonance imaging (MRI); brain atrophy was also assessed by CT and T1-weighted MRI. Extensive PVH showed a stronger correlation with age related atrophy than mild or absent PVH. The relative volume of brain affected by PVH, calculated by computer, also correlated with brain atrophy, especially ventricular enlargement. The effects of PVH on brain ageing and atrophy is discussed. PMID- 8433788 TI - Magnetic resonance imaging of the brain in Wilson's disease. AB - Eight patients with Wilson's disease (WD) were studied by magnetic resonance imaging (MRI) of the brain; seven also underwent X-ray computed tomography (CT) of the brain. We describe the changes in the brain and try to correlate them with the clinical manifestations and progress of the disease. Six patients were symptomatic, with predominantly neurological problems. Two were asymptomatic, diagnosed upon screening siblings of index cases. Of the six symptomatic patients, five had basal ganglia lesions, combined in four with brain stem changes; in one with only brain stem abnormalities, clinical findings were minimal despite pronounced MRI changes. In three patients MRI abnormalities regressed following chelating therapy. MRI can contribute to documentation of early neurological involvement in WD, especially in patients with no abnormalities on CT. However, MRI changes may not correlate with clinical presentation or response to therapy. PMID- 8433789 TI - Magnetic resonance imaging of the brain in Wilson's disease. AB - Fifteen patients with Wilson's disease were examined, using spin-echo (SE) and gradient-echo (GE) sequences with 0.5 T and 1.5 T magnetic resonance (MR) imagers. They fell into three groups: groups 1 and 2 were examined retrospectively after 3-18 years of treatment, while group 3 was examined prospectively from the start of treatment, after recommencement of treatment, or inadequate treatment. MRI was sensitive to changes in the basal ganglia at sites typical of Wilson's disease and was useful for documenting the effects of treatment. It was found necessary to estimate the relaxation times T1 and T2, to better assess improvement or transient worsening of the disease in the prospective group. Residual cavitation and gliosis could be distinguished in the retrospective group using a subtraction technique. PMID- 8433790 TI - Gadolinium-enhanced MRI in central nervous system Behcet's disease. AB - Two cases of central nervous system Behcet's disease, studied by gadolinium enhanced MRI, are presented. In one patient, whose clinical picture was dominated by a brain syndrome, the gadolinium enhancement resolved with clinical improvement, although the hyperintense areas in the mesencephalon on T2-weighted images persisted. In the second, who had a pseudobulbar palsy and a mild right hemiparesis, there were many abnormal areas, but an enhancing focus in the posterior limb of the left internal capsule was probably the lesion responsible for the hemiparesis. PMID- 8433791 TI - Behcet's disease presenting as a cerebral tumour. PMID- 8433792 TI - Neurosarcoidosis with unusual MRI findings. AB - This 53-year-old white male presented with a 4-month-history of weakness and pain. Despite an initial partial response to steroid therapy, his neurologic deterioration progressed culminating in paraparesis, paresthesias, urinary incontinence, altered mentation and a 20 lb weight loss. A gadolinium-enhanced MRI study showed a pattern suggestive of perivascular involvement. A subsequent cerebral biopsy was diagnostic for neurosarcoidosis. PMID- 8433793 TI - Unilocular orbital, cerebral and intraventricular hydatid cysts: CT diagnosis. AB - A 10-year-old girl with surgically proven unilocular hydatid cysts within the frontal horn of the right lateral ventricle, in the right orbit and another the left frontal region is reported. The intraventricular cyst was diagnosed on CT examination with intrathecal contrast medium injected via lumbar puncture. PMID- 8433794 TI - Incidental high-intensity foci in white matter on T2-weighted magnetic resonance imaging. Frequency and clinical significance in symptom-free adults. AB - The clinical significance of high-intensity foci in the white matter on magnetic resonance images of the brain was studied in 351 adults. The foci frequently occurred in the corona radiata and centrum semiovale. The frequency and extent of the foci were closely related to age and to a previous history of cerebrovascular disease. Patients without such a history but with risk factors for cerebrovascular disease tended to have these foci more frequently than those without risk factors. PMID- 8433795 TI - Detection of optic nerve lesions in optic neuritis using frequency-selective fat saturation sequences. AB - MRI was performed on seven patients with acute optic neuritis, using two sequences which suppress the signal from orbital fat: frequency-selective fat saturation and inversion recovery with a short inversion time. Lesions were seen on both sequences in all the symptomatic optic nerves studied. PMID- 8433796 TI - Local intra-arterial fibrinolytic therapy in patients with stroke: urokinase versus recombinant tissue plasminogen activator (r-TPA). AB - A group of 59 patients with stroke due to acute vertebrobasilar or carotid territory occlusion have been treated by local intra-arterial fibrinolysis (LIF). A high recanalisation rate was accomplished with either urokinase or recombinant tissue plasminogen activator (r-TPA). However, with either substance, even if a high dose was used, recanalisation was a time-consuming process which usually took 120 min. A reasonable explanation for the lack of effectiveness of these plasminogen-activating substances might be a deficit of substrate, e.g. plasminogen, in aged thrombus. LIF was capable of improving clinical outcome in acute vertebrobasilar artery occlusion, reducing mortality to 50% in patients fulfilling inclusion criteria. In the carotid territory multiple occlusions had a poor prognosis while good clinical results could be achieved in occlusions of the proximal middle cerebral artery or single branches. PMID- 8433797 TI - Decreased signal intensity of the putamen and the caudate nucleus in Wilson disease of the brain. PMID- 8433798 TI - The Lucien Appel Prize. PMID- 8433799 TI - Early diagnosis of perinatal cerebral lesions in apparently normal full-term newborns by ultrasound of the brain. AB - The brains of 1000 consecutive, clinically normal, full-term neonate without signs of perinatal distress were examined by ultrasound 3 days postpartum. We found 35 cases of intracranial haemorrhage (periventricular, choroid plexus and intraventricular); 34 possible sequelae of bleeding (subependymal and choroid plexus pseudocysts; local dilatation of the lateral ventricles) and 21 morphological aberrations. Most of these 90 abnormalities were checked several times. Four children with intracranial haemorrhage developed symptoms (3 hemipareses, 1 infantile spasm) within a year of birth. No child without sonographic abnormalities has so far been recognized as developing a clinical deficit. PMID- 8433800 TI - Infantile panthalamic infarct with a striking sonographic finding: the "bright thalamus". AB - A "bright thalamus" is not uncommonly observed in cranial sonograms of asphyxiated neonates, but not those of older infants. Three infants, aged 9-14 months, developed acute onset of seizures and disturbance of consciousness after a minor prodromal illness. Bilateral thalamic infarcts were demonstrated by ultrasonography and CT. One patient expired from causes not directly related to the infarcts; the other two survived with severe neurological sequelae. PMID- 8433801 TI - Magnetic resonance angiography of cerebral developmental venous anomalies: its role in differential diagnosis. AB - CT, MRI and contrast angiography of 20 patients with 21 developmental venous anomalies (DVAs), so-called venous angiomas, were compared with magnetic resonance angiography employing a two-dimensional time-of-flight technique (2D MRA). MRA was diagnostic in 17 DVAs, when both the primary 2D slices and the maximum-intensity-projection images were read. Contrast angiography still provides the best visualization of both DVA components: dilated medullary veins and transcerebral draining vein; however, it is an invasive procedure and delivers no information about brain parenchyma. We regard MRI as necessary in cases with a suspected DVA because of the high rate of association with cavernomas: 33% in this study. Acute neurological symptoms were caused by haemorrhage from an associated cavernoma and not from the DVA in 4 such cases. Thus MRA combined with MRI obviates angiography in most cases and offers a noninvasive diagnostic strategy adequate for DVAs. PMID- 8433802 TI - Glutathione peroxidase, glial cells and Parkinson's disease. AB - Hyperoxidation phenomena are suspected to be involved in dopaminergic cell death in Parkinson's disease, which affects preferentially the neuromelanin-containing dopaminergic neurons of the substantia nigra. Glutathione peroxidase is the major protective enzyme against hydrogen peroxide toxicity. The distribution of glutathione peroxidase-containing cells was investigated by immunohistochemistry in the midbrain of four control subjects and four patients with Parkinson's disease. (1) Glutathione peroxidase-like immunoreactivity was detected exclusively in glial cells. (2) In control brains, the density of glutathione peroxidase-positive cells was higher in the vicinity of the dopaminergic cell groups known to be resistant to the pathological process of Parkinson's disease. (3) In Parkinson's disease, an increased density of glutathione peroxidase immunostained cells was observed, surrounding the surviving dopaminergic neurons. The increase in glutathione peroxidase-containing cells was correlated with the severity in dopaminergic cell loss in the respective cell groups. The data suggest that in control brains, a low density of glutathione peroxidase-positive cells surround the dopaminergic neurons the most vulnerable to Parkinson's disease, and that in parkinsonian brains, the increased number of glutathione peroxidase-positive cells may contribute to protect neurons against pathological death. Thus, the amount of glutathione peroxidase protein-containing cells may be critical for a protective effect against oxidative stress, although it cannot be excluded that the level of the enzyme activity remains the crucial factor. PMID- 8433803 TI - Up-regulation of dopamine receptors in the brain of the spontaneously hypertensive rat: an autoradiographic analysis. AB - Recent evidence points to a dysfunction of brain dopaminergic mechanisms in the spontaneously hypertensive rat. Using in vitro receptor autoradiography, we assessed the density of D1 and D2 dopamine receptors in the brain of spontaneously hypertensive rats and their normotensive controls the Wistar-Kyoto rat. Brain sections from five- and 15-week-old rats were incubated with 1 nM [3H]SCH 23390 (D1 receptor antagonist) or 15 nM [3H]sulpiride (D2 receptor antagonist), and exposed along with radioactive standards to 3H-Hyperfilm. The binding density of selected brain regions (anteromedial prefrontal cortex, cingulate cortex, lateral septal nucleus, nucleus accumbens, caudate-putamen, globus pallidus, amygdaloid complex) were quantified using computer-assisted densitometry. These experiments showed a significant increase in the binding density of [3H]SCH 23390 in the nucleus accumbens and caudate-putamen of five- and 15-week-old spontaneously hypertensive rats. The binding density of [3H]SCH 23390 was increased in the lateral septal nucleus of five-week-old and globus pallidus of 15-week-old spontaneously hypertensive rats. The binding density of [3H]sulpiride was also greater in the nucleus accumbens of five-week-old spontaneously hypertensive rats. The present investigation demonstrates an up regulation of D1 dopamine receptors in spontaneously hypertensive rats with established hypertension. More importantly, up-regulation of D1 and D2 dopamine receptors in the striatum of young prehypertensive spontaneously hypertensive rats suggests that dopamine may be involved in the pathogenesis of hypertension in this strain of genetically hypertensive rats. PMID- 8433804 TI - The distribution of excitatory amino acid receptors on acutely dissociated dorsal horn neurons from postnatal rats. AB - Excitatory amino acid receptor distribution was mapped on acutely dissociated neurons from postnatal rat spinal cord dorsal horn. N-methyl D-aspartate, quisqualate and kainate were applied to multiple locations along the somal and dendritic surfaces of voltage-clamped neurons by means of a pressure application system. To partially compensate for the decrement of response amplitude due to current loss between the site of activation on the dendrite and the recording electrode at the soma, a solution containing 0.15 M KCl was applied on the cell bodies and dendrites of some cells to estimate an empirical length constant. In the majority of the cells tested, the dendritic membrane had regions of higher sensitivity to excitatory amino acid agonists than the somatic membrane, with dendritic response amplitudes reaching more than seven times those at the cell body. A comparison of the relative changes in sensitivity between each combination of two of the three excitatory amino acid agonists along the same dendrite showed different patterns of agonist sensitivity along the dendrite in the majority of the cells. These data were obtained from dorsal horn neurons that had developed and formed synaptic connections in vivo. They demonstrate that in contrast to observations made on ventral horn neurons, receptor density for all the excitatory amino acid receptors on dorsal horn neurons, including the N methyl-D-aspartate receptor, are generally higher on the dendrites than on the soma. Further, these results are similar to those obtained from dorsal horn neurons grown in culture. PMID- 8433805 TI - The substantia innominata complex and the peripeduncular nucleus in orofacial dyskinesia: a pharmacological and anatomical study in cats. AB - It has been shown that orofacial dyskinesia, i.e. a syndrome of abnormal involuntary movements of the facial muscles, can be elicited from the sub commissural part of the globus pallidus and the adjoining dorsal parts of the extended amygdala in cats. Until now it is unknown whether the peripeduncular nucleus, which receives input from these structures according to anterograde tracing studies, plays a role in the funneling of orofacial dyskinesia to lower output stations. In the present study the connection of the subcommissural part of the globus pallidus and dorsal parts of the extended amygdala with the peripeduncular nucleus was investigated anatomically, using cholera toxin subunit B as a retrograde tracer, and functionally, using intracerebral injections of GABAergic compounds. The anatomical data show that the sub-commissural part of the globus pallidus and dorsal parts of the extended amygdala were marked by cholera toxin sub-unit B-immunoreactive cells following injections of this retrograde tracer into the peripeduncular nucleus. Thus, it could be confirmed that the peripeduncular nucleus receives input from the sub-commissural part of the globus pallidus and dorsal parts of the extended amygdala. Still, the orofacial dyskinesia elicited by local injections of the GABA antagonist picrotoxin (500 ng/0.5 microliters) into the sub-commissural part of the globus pallidus and dorsal extended amygdala was only in part attenuated by local injections of the GABA agonist muscimol (100 ng/l microliters) into the peripeduncular nucleus. Only the number of tongue protrusions was significantly attenuated, but not that of the ear and cheek movements. Furthermore, tongue protrusions, but no additional oral movements, were elicited by picrotoxin injections (375-500 ng) into the peripeduncular nucleus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433806 TI - Increase in the number of intrafusal muscle fibres in rat muscles after neonatal motor denervation. AB - Rat muscle spindles disintegrate after total neonatal muscle denervation in which both sensory and motor axons are cut, but develop almost normally during the first three weeks after neonatal de-efferentation, attaining the usual complement of four intrafusal fibres, two bag and two chain fibres. Thereafter additional intrafusal fibres differentiate in most of the de-efferented spindles. We have examined the development of supernumerary fibres in muscle spindles of the rat hind limb muscles one to four months after neonatal de-efferentation using transmission electron microscopy. Additional intrafusal fibres originate both from activated intrafusal myosatellites and by different forms of fibre division. In a sample of 27 muscle spindles examined along the A zone five weeks after de efferentation, the mean number of intrafusal fibre profiles increased almost two fold to 7.9 +/- 3.3 (S.D.). Up to 20 intrafusal fibre profiles per spindle cross section were found in muscles de-efferented for four months. The supernumerary fibres were apparently derived from all three intrafusal fibre types, but predominantly from the chain fibres. It is noteworthy that de-efferentation which causes wasting of extrafusal muscle initiates myogenesis and maintains additional intrafusal fibres within the spindle capsules. PMID- 8433807 TI - Fusimotor-free spindles in reinnervated muscles of neonatal rats treated with nerve growth factor. AB - Crushing the nerve to the medial gastrocnemius muscle in newborn rats and administering nerve growth factor afterwards results in a reinnervated muscle containing supernumerary muscle spindles. The structure and innervation of 88 spindles in the reinnervated muscles were reconstructed from serial thick and thin transverse sections at 30-35 days after the nerve crush, and compared to those of five control spindles. The spindles consisted of one to four small diameter encapsulated fibers with features of nuclear chain intrafusal fibers, or infrequently a nuclear bag intrafusal fiber. Some of the spindles were located within a capsule that also contained an extrafusal fiber. Each spindle was innervated by an afferent with features of the primary afferent. The density of secondary afferents was lower in reinnervated muscles than in controls. Endplates were observed on extrafusal fibers in the experimental muscles, attesting to restoration of skeletomotor (alpha) innervation after the nerve crush. However, 78% of the experimental spindles were entirely devoid of efferent innervation. The remainder received either one or two fusimotor (gamma) axons or a skeletofusimotor (beta) axon, compared to the six to eight motor axons that innervated control spindles. The presence of supernumerary spindles composed of fibers that resemble normal intrafusal fibers in the absence of motor innervation suggests that afferents alone can induce the formation and subsequent differentiation of intrafusal fibers in nerve-crushed muscles of neonatal rats. In addition, the paucity of gamma innervation in nerve-crushed muscles suggests that immature gamma neurons are more susceptible than spindle afferents or alpha efferents to cell death after axotomy at birth. PMID- 8433808 TI - MK-801 protects against neuronal injury induced by electrical stimulation. AB - The ability of MK-801, a non-competitive N-methyl-D-aspartate receptor antagonist, to protect neurons in the cerebral cortex from injury induced by prolonged electrical stimulation was assessed in cats. Platinum disc electrodes 8.0 mm in diameter and with a surface area of 0.5 cm2 were implanted in the subdural space over the parietal cortex. Ten days after implantation of the electrodes, all animals received continuous stimulation for 7 h using charge balanced, cathodic-first, controlled current pulses with a charge density of 20 microC/cm2 and a charge/phase of 10 microC/phase. They received either no MK-801, or 0.33 or 5.0 mg/kg (i.v.) administered intravenously, just before the start of the stimulation. Immediately following the stimulation, the animals were perfused and the cerebral cortex examined by light microscopy at eight sites beneath the electrodes. Neuronal damage in the form of shrunken, hyperchromic neurons and perineuronal halos was present only beneath the stimulating electrodes; damage was moderate to severe in stimulated animals that had not received MK-801, slight in animals receiving 0.33 mg/kg, and none to slight in animals receiving 5.0 mg/kg. These results indicate that MK-801, in an apparently dose-dependent fashion, provides substantial but not complete protection against neuronal injury induced by prolonged electrical stimulation. Thus prolonged electrical stimulation can be added to the list of neuropathologic conditions which involve glutamate-induced excitotoxic damage via the N-methyl-D-aspartate receptor. The results also support the hypothesis of neuronal hyperactivity as a principal cause of electrically-induced injury in the central nervous system. The implications for design of protocols for functional electrical stimulation are discussed. PMID- 8433809 TI - Optical monitoring of early appearance of spontaneous membrane potential changes in the embryonic chick medulla oblongata using a voltage-sensitive dye. AB - Using a voltage-sensitive merocyanine-rhodamine dye (NK2761) and a 12 x 12 element photodiode matrix array, we recorded optically spontaneous membrane potential changes in a slice preparation from the embryonic chick brain stem during early development. The spontaneous optical signals, related to membrane potential changes, showed a simple monophasic shape with a relatively long duration, and they were synchronized among the different regions in the medulla oblongata. The spontaneous signals were first detected from seven-day-old embryos, and were not present in six-day-old embryos. The spontaneous signals appeared sporadically, and their frequency was very low. Three modes of optical signals termed "singlet-mode", "doublet-mode", and "triplet-mode" were observed. In the doublet- and triplet-modes, the spatial pattern of the first signal was primarily similar to that of the singlet-mode signal, whereas the signal size and spatial extent of the second and third signals appeared to decay. PMID- 8433810 TI - Developing a stable bilateral model of parkinsonism in rhesus monkeys. AB - The non-human primate models of Parkinson's disease which have been developed using the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine) have proven to be either unstable or variable, or to display only a limited subset of parkinsonian features. The present study examined a new two-stage lesion approach in which MPTP was administered via the carotid arteries. The first infusion through one artery produced a hemiparkinsonian state and was followed several months later by a second MPTP infusion into the contralateral carotid artery to induce bilateral parkinsonism. Animals receiving lesions were evaluated using a battery of tests which included a monkey parkinsonism rating scale, a movement time-task and continuous monitoring of home cage activity. All animals monitored showed significant decreases in activity levels of up to 95% following the second lesion. These decreased activity levels remained stable throughout the observation period of up to 12 months postlesion. In addition to the decreased home cage activity, bilaterally lesioned animals displayed bilateral parkinsonian features including akinesia, bradykinesia, rigidity, tremor and balance and gait disturbances which were stable, following an acute period of up to 45 days, for the remainder of the study. Administration of levodopa increased activity levels and reduced motor dysfunctions. Thus, a two-stage bilateral lesion approach, utilizing the neurotoxin MPTP, appears to provide a less variable and relatively stable model of bilateral Parkinson's disease in nonhuman primates. Treated animals display the cardinal features of parkinsonism and respond appropriately to the standard antiparkinsonian drug, levodopa. PMID- 8433811 TI - GABA responses and their partial occlusion by glycine in cultured rat medullary neurons. AB - Whole-cell current responses to bath application of GABA and glycine were studied in medullary neurons cultured from embryonic rats. Two current components were seen in the responses to bath application of GABA, one component which desensitized and another which did not. These two current components have different dose-response characteristics for GABA, with the nondesensitizing component being activated more effectively and reaching its peak amplitude at lower agonist concentrations than the desensitizing one. The agonist concentrations producing half of the maximum responses are 2.8 +/- 0.3 (+/- S.E.M., n = 9) and 14.7 +/- 2.7 (n = 5) microM for the nondesensitizing and desensitizing components, respectively. The two current components for GABA are differentially affected by the antagonists, picrotoxin and bicuculline. The antagonist concentrations which block 50% of the control desensitizing and nondesensitizing responses to GABA are 33 and 320 microM for picrotoxin, and 3 and 50 microM for bicuculline, respectively. Thus, the characteristics of the GABA responses are analogous to those described previously for glycine in that there are two components which are differentially sensitive to agonist concentration [Lewis et al. (1991) J. Neurophysiol, 40, 1178-1187]. We now find there is occlusion between the responses to GABA and glycine, indicating that they share a population of receptors or channels. The occlusion was incomplete (< 80%) in half of the cells, suggesting that both agonists also activate unique receptors. Furthermore, the current responses to 35 microM GABA are blocked by the glycinergic antagonist, strychnine, with half-maximal blocking concentrations equal to 2 and 30 microM for the desensitizing and nondesensitizing components, respectively. This strychnine sensitivity is less than that for the glycine receptor. At the same time, the current responses to 100 microM glycine are sensitive to the GABAergic antagonists, picrotoxin and bicuculline. The half maximal blocking concentrations are 36 and 120 microM picrotoxin, and 120 and 500 microM bicuculline, for the desensitizing and nondesensitizing components of the glycine response, respectively. Consequently, these results suggest that these cultured cells have at least three types of inhibitory receptors: glycine receptors, GABA receptors and GABA/glycine receptors, with all three receptors sensitive to block by strychnine, bicuculline and picrotoxin. The GABA/glycine receptor may be an immature form of the inhibitory receptor. Alternatively, some GABA and glycine receptors may have common ionophores. PMID- 8433812 TI - Phototherapeutic keratectomy. PMID- 8433813 TI - Hypercorrection of hypotropia in Graves ophthalmopathy. PMID- 8433814 TI - Prognosis for keratoplasty in Acanthamoeba keratitis. AB - STUDY: Penetrating keratoplasty (PK) was undertaken between 1985-1991 at Moorfields Eye Hospital in 13 eyes (19 PKs) of 11 patients who developed Acanthamoeba keratitis. Infection was ultimately controlled in all cases. Retrospective analysis was undertaken to establish risk factors for PK. Six eyes were quiet and 7 had uncontrolled infection at the time of keratoplasty. The outcome for these was compared. COMPLICATIONS: Complications included cataract in 50% of quiet eyes and 100% of inflamed eyes. Intumescent cataract resulted in glaucoma requiring drainage surgery in 4 eyes. Graft rejection episodes occurred in 50% of quiet eyes, but were treated aggressively and did not cause graft failure. RESULTS: Graft survival was excellent for quiet eyes, but was compromised by recurrent infection in inflamed eyes and 6 patients were regrafted. Survival compared poorly with grafting for active herpetic or bacterial keratitis, indicating that early diagnosis and treatment are essential for adequate control of this disease. PMID- 8433815 TI - Laser photocoagulation of experimental corneal stromal vascularization. Efficacy and histopathology. AB - BACKGROUND: Conventional treatment of corneal stromal vascularization is often inadequate. The authors developed a rabbit model of corneal stromal vascularization, treated it with laser photocoagulation, and then studied the histopathology. METHODS: A reproducible model of corneal stromal vascularization was developed in albino rabbits by injecting sodium hydroxide into the corneal stroma. Corneal stromal vascularization was produced in both eyes of 13 rabbits, and treated after stabilization at 5 weeks with 577-nm yellow dye laser in 1 eye of each rabbit. Seven rabbits were followed for 6 months with corneal angiography and photography, and the corneal stromal vascularization quantified with a grid. The other 6 rabbits were killed at 1, 4, 8, 24, 48 hours, and 6 days after laser photocoagulation and examined by light and transmission electron microscopy. RESULTS: Stable corneal stromal vascularization was observed in the anterior and midstroma for at least 6 months in the model. Laser photocoagulation reduced corneal stromal vascularization significantly compared with the controls (P < or = 0.05), resulting in 40.7% +/- 5.0%, 45.3% +/- 3.3%, and 34.9% +/- 5.2% (mean +/ standard error of the mean) reduction at 2, 4, and 6 months, respectively. Maximum inflammatory cell infiltrates were detected at 8 hours after laser photocoagulation, which diminished markedly at 6 days. The stroma of unlasered eyes showed no inflammatory cells and considerably more patent blood vessels than the lasered eyes. In the lasered eyes, transmission electron microscopy showed damaged vascular endothelial cells, extravasated erythrocytes, haphazardly arranged collagen fibrils, thrombus formation, and ghost vessels in the stroma. No damage was observed in the deep corneal stroma or endothelium in the lasered eyes. CONCLUSION: Laser photocoagulation is effective in reducing corneal stromal vascularization in this model for at least 6 months. It does not damage the deeper stroma or endothelium. PMID- 8433816 TI - Changes in keratometric astigmatism after suture removal more than one year after penetrating keratoplasty. AB - BACKGROUND/PURPOSE: Selective removal of interrupted sutures and adjustment of a running suture can minimize astigmatism after penetrating keratoplasty, but the long-term effects of early suture manipulations remain largely unknown. The authors tested the hypothesis that the cornea becomes "fixed" more than 1 year after keratoplasty so that desirable refractive results will remain when all sutures are eventually removed. METHODS: The authors reviewed retrospectively the changes in astigmatism that occurred when all remaining sutures were removed from 162 eyes 1 to 6 years after penetrating keratoplasty. Single-running sutures were used in 130 eyes, double-running sutures in 20 eyes, and a combination of interrupted and running sutures in 12 eyes. RESULTS: Removal of single-running sutures caused an average decrease in astigmatism of 0.52 diopters (D) from 6.10 +/- 4.41 D to 5.57 +/- 3.14 D. However, the astigmatism in 62% of eyes changed 2 or more D (range, 11.94 to -17.87 D), and the range changed more than 20 degrees in 55% of eyes. The average vectorial change was 6.5 +/- 4.3 D (range, 0.59 to 19.8 D). There was no decrease in the amount of astigmatic change with increasing time between surgery and suture removal. Graft size and diagnosis had no effect on the amount of astigmatic change. Astigmatic errors became stable, with less than 1 D of change between successive examinations within 6 months after suture removal. Similar results were obtained for eyes with double-running and interrupted-running sutures. CONCLUSIONS: Corneal astigmatism may change unpredictably and by large amounts when all remaining sutures are removed 1 to 6 years after penetrating keratoplasty. PMID- 8433818 TI - Fusion after surgical alignment of longstanding strabismus in adults. AB - BACKGROUND: Fusion and the development of the monofixation syndrome are well recognized after surgical alignment of congenital esotropia to within 8 delta of orthotropia. However, in adults with longstanding strabismus and a history of congenital esotropia who are not surgically aligned within the first few years of life, the prognosis for the development of fusion is believed to be poor. METHODS AND RESULTS: Twenty-four adults, 12 with a history of congenital esotropia (onset before 6 months age), 1 of congenital exotropia, and 11 with the onset of esotropia between 6 months and 2 years, were included in this study. All patients had longstanding strabismus, and none had been surgically aligned within the first 2 years of life. No patient had visual acuity worse than 20/30 in the worse eye. Preoperatively, no patient demonstrated fusion with the red glass test, Worth four-dot, or Titmus test. Postoperatively, all were aligned to within 8 delta of orthotropia, and all demonstrated peripheral fusion with the Worth four dot at near. Twelve patients (50%), 8 of whom were in the congenital group, achieved stereopsis of 200 seconds of arc or better using the Titmus stereo test. CONCLUSION: These findings suggest that surgery in this group of patients not only eliminates the ocular alignment deformity but can confer the functional benefits of fusion and increased field of binocular vision. PMID- 8433817 TI - Corneal topographic alterations in normal contact lens wearers. AB - PURPOSE: The purpose of this study is to investigate the corneal topography of visually normal asymptomatic eyes that wore rigid and soft contact lenses compared with visually normal eyes that had never worn contact lenses. METHODS: Thirty-seven normal corneas and 74 corneas in asymptomatic eyes that wore rigid (12 polymethylmethacrylate and 23 gas-permeable) and soft (26 daily-wear and 13 extended-wear) contact lenses for refractive correction underwent slit-lamp examination, keratometry, computer-assisted topographic analysis, refraction, and rigid contact lens over-refraction. RESULTS: Topographic abnormalities tended to be more common and more severe in corneas that wore rigid contact lenses, but significant changes were noted in some eyes that wore daily-wear or extended-wear soft contact lenses. A number of eyes in the rigid polymethylmethacrylate (9 of 12) and rigid gas-permeable (6 of 23) contact lens groups had a correlation between the most frequent resting position of the contact lens and the corneal topography, with relative flattening of the corneal contour beneath a decentered lens. A total of 10 eyes in the rigid contact lens groups had a 1-line decrease in best spectacle-corrected visual acuity attributable to contact lens-induced topographic abnormalities. CONCLUSIONS: Corneal topographic alterations are common in asymptomatic contact lens wearers and are frequently detectable only with computer-assisted topographic analysis. It is important that topographic abnormalities be excluded in contact lens wearing eyes before refractive surgical procedures. PMID- 8433819 TI - Olivopontocerebellar atrophy with retinal degeneration. An electroretinographic and histopathologic investigation. AB - BACKGROUND: Olivopontocerebellar atrophy is an uncommon disorder with variable clinical manifestations that affects the cerebellum, the spinocerebellar tracts, and other structures of the brainstem. A deficiency of glutamate dehydrogenase, which results in an excess of glutamate, has been suggested to play a role in the pathogenesis of olivopontocerebellar atrophy. In experimental animals, toxic levels of glutamate are known to cause a selective loss of the b-wave on electroretinographic (ERG) testing and a degeneration of the inner retinal layers. One of the subtypes of olivopontocerebellar atrophy, type II, according to Harding's classification, is associated with retinal degeneration. METHODS: The authors describe the ophthalmologic and ERG findings in a family with olivopontocerebellar atrophy type II. Histopathologic study of an eye from a 6 year-old family member who died of severe neurologic deterioration secondary to olivopontocerebellar atrophy type II was performed. RESULTS: Electroretinographic changes may be present in affected family members who are entirely asymptomatic and have a normal ophthalmologic evaluation. The changes on the ERG in one patient suggest that cone dysfunction is one of the subtle changes that may be seen in olivopontocerebellar atrophy type II. Our ERG results did not show a selective loss of the b-wave but instead showed a loss of both the a-wave and b wave in affected family members. Results of light and electron microscopic examination showed diffuse and extensive degeneration of the photoreceptors involving both rods and cones, the most prominent changes being present in the macula. An amorphous debris, presumably degenerated photoreceptors, was noted between the outer nuclear layer and retinal pigment epithelium. CONCLUSION: Patients with olivopontocerebellar atrophy type II have photoreceptor abnormalities as revealed in abnormal ERGs seen in many patients and histopathologic study of an autopsy eye from an affected 6-year-old boy. Our results do not support the hypothesis that glutamate toxicity may be responsible for the development of retinal degeneration in this condition. PMID- 8433820 TI - Central retinal vein occlusion associated with retinal arteriovenous malformation. AB - PURPOSE/BACKGROUND: Retinal arteriovenous malformations can be seen in a variety of ways and have multiple, associated, ocular changes that can affect vision. The authors report two cases of retinal arteriovenous malformation. In each case, a central retinal vein occlusion developed. METHODS: Each patient underwent clinical examination and fluorescein angiography. One patient was followed over a long period of time. CONCLUSION: The authors propose that a turbulent flow, high intravascular volume, and arteriolar pressure in the venous side of the retinal arteriovenous malformation may lead to vessel wall damage, thrombosis, and occlusion. They also suggest that compression of the central retinal vein by the mass effect of the arteriovenous malformation on the optic nerve further leads to turbulence and thrombosis. PMID- 8433821 TI - Additional failures after filtering with 5-FU. PMID- 8433822 TI - Fish-hook injuries. PMID- 8433823 TI - Fish-hook injuries. PMID- 8433824 TI - Asymmetric distribution of arteriovenous crossings in the normal retina. AB - BACKGROUND: Recently, there has been renewed interest in the orientation of the crossing retinal vessels at arteriovenous intersections, particularly as it relates to the risk of branch vein occlusion. Little is known about the distribution of the two types of crossings in the normal retina. METHODS: The authors studied standard fundus photographs of 51 subjects without retinal disease. Arteriovenous crossings were analyzed for fundus location and relative orientation of the crossing vessels (vein-posterior or vein-anterior). FINDINGS: In the superotemporal quadrant, crossings were distributed closer to the optic disc (P < 0.001), and a greater proportion of crossings were vein-posterior (P = 0.01) than in the inferotemporal quadrant. As a result, within a 3-disc diameter (DD) radius of the optic disc, there were significantly more vein-posterior crossings in the superotemporal than in the inferotemporal quadrant (P < 0.001). CONCLUSION: These findings further define normal retinal vascular anatomy and may explain the predilection for branch retinal vein occlusions to occur in the superotemporal quadrant. PMID- 8433825 TI - Pathologic findings in the retinal pigment epitheliopathy associated with the amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam. AB - BACKGROUND: A pigment epitheliopathy that resembles ophthalmomyiasis interna occurs in approximately 10% of a large sample of the Chamorro population of Guam age 39 years or older; the rate is approximately 50% among those who have amyotrophic lateral sclerosis or Parkinsonism-dementia complex (lytico bodig). METHODS: Since publication of an earlier clinical report of affected patients, several of them have died of their neurologic disease, and their eyes were obtained for pathologic study. This is the first pathologic report of the retinal pigment epitheliopathy seen in the setting of amyotrophic lateral sclerosis/Parkinsonism-dementia complex of Guam and is based on examination of 13 eyes from 7 patients. RESULTS/CONCLUSION: Focal areas of attenuation of the retinal pigment epithelium in association with a reduced amount of intracellular pigment correlated with the funduscopic and gross appearance. No larvae were seen, and there was no evidence of inflammation. The pathogenesis of this pigment epitheliopathy remains undetermined. PMID- 8433826 TI - Correlation between lipids extracted from Bruch's membrane and age. AB - BACKGROUND: There is increasing circumstantial evidence that the chemical composition of the deposits in Bruch's membrane influences the clinical outcome in age-related macular disease. In particular, it has been postulated that deposition of neutral lipids in Bruch's membrane may cause hydrophobicity and predispose to detachment of the retinal pigment epithelium and cause functional loss. METHODS: Analysis of the lipid extracted from Bruch's membrane of eye bank eyes from donors of different ages has been undertaken using thin layer and gas chromatography. No clinical information was available concerning any previous eye disease. RESULTS: It is shown that the lipid extracted increases with the age of the donor, and that the total quantity and ratio of neutral fats to phospholipids varies widely from one specimen to another from donors older than 60 years of age. The ratios of the different phospholipids imply that they are not derived from blood. CONCLUSION: The results are compatible with the concept of hydrophobicity developing with age in Bruch's membrane. PMID- 8433827 TI - Clinical disc biometry in early glaucoma. AB - PURPOSE: To assess the potential of a clinical method of optic disc measurement in the detection of early neuroretinal rim loss in glaucoma. METHODS: A method of disc biometry based on indirect ophthalmoscopy was used to estimate disc and neuroretinal rim areas in 81 ocular hypertensive eyes of 43 patients and in 28 fellow eyes with normal visual fields of patients with unilateral visual field loss from primary open-angle glaucoma. The results were compared with those from age-matched visually normal patients. RESULTS: Neuroretinal rim area was significantly smaller in both hypertensive and fellow eye groups compared with controls (P < 0.0001; P = 0.0009). Disc area also was smaller in both groups (P = 0.0034; P = 0.046); however, this was inadequate to explain the differences in rim area, which, when corrected for disc size, were still highly significant (P < 0.0001; P = 0.0001). CONCLUSION: The differences in neuroretinal rim area observed are likely to indicate that a proportion of the eyes studied had suffered a reduction of neuroretinal rim area, which was measurable by this method at a stage before the development of demonstrable visual field loss. PMID- 8433828 TI - Confocal laser scanning ophthalmoscope. Reproducibility of optic nerve head topographic measurements with the confocal laser scanning ophthalmoscope. AB - BACKGROUND: Glaucoma is an optic neuropathy in which changes in the appearance of both the optic nerve head and the surrounding tissues are important in both diagnosing its presence and progression. Accurate methods to objectively document the appearance of the optic nerve are necessary. The confocal laser scanning ophthalmoscope (Zeiss) is a new prototype instrument that may have the capability to accurately perform this function. METHODS: The authors performed a prospective pilot study evaluating the ability of the confocal laser scanning ophthalmoscope to reproduce three-dimensional optic nerve images. Each retinal image contained 600,000 bytes of information. Thirty discrete images of the right optic nerves of 19 visually normal volunteers were obtained. Depth measurements were compared from the same 100 x 100 micron areas (neighborhoods). RESULTS: Image comparisons found the variability of depth measurements for the entire image were within 102 microns (95% confidence interval). Sixty percent of the depth measurements were reproducible within 100 microns. Variability of the depth measurements was greatest where the neuroretinal rim sloped at the edge of the optic cup and lowest in the peripapillary area. CONCLUSION: The confocal laser scanning ophthalmoscope has the potential to be a safe, rapid, and reproducible method of imaging ocular structures. PMID- 8433829 TI - Pattern of glaucomatous neuroretinal rim loss. AB - BACKGROUND: In advancing glaucomatous optic nerve damage, the area of the neuroretinal rim progressively diminishes, and its form continuously changes. This cross-sectional study was undertaken to establish a set pattern behind glaucomatous rim loss. METHODS: The authors evaluated morphometrically stereo color optic disc photographs of 801 glaucomatous eyes and 496 visually normal eyes. RESULTS: Compared with the visually normal eyes, glaucomatous neuroretinal rim loss occurred in all sectors of the optic disc with regional preferences depending on the stage of the disease. In the eyes with modest glaucomatous damage, rim loss was usually most pronounced in the inferotemporal disc region. In the eyes with moderately progressed glaucomatous changes, rim was decreased most markedly in the superotemporal sector, then in the temporal horizontal area, the nasal inferior region, and finally in the superior nasal sector. In very advanced glaucoma, rim remnants usually were present only in the nasal disc region. At that stage, they were significantly larger in the superior nasal region than in the nasal inferior area. CONCLUSION: Other than occurring in a diffuse way, glaucomatous neuroretinal rim loss took place in a sequence of sectors. Generally, it began in the inferotemporal disc region and then progressed to the superotemporal, the temporal horizontal, the inferior nasal, and finally the superior nasal sectors. This correlates with the progression of visual field defects and the morphology of the lamina cribrosa. This finding may be important for "early" glaucoma diagnosis. PMID- 8433830 TI - Sectorization of the central 30 degrees visual field in glaucoma. AB - PURPOSE: To determine an optimal sector pattern of the central 30 degrees visual field in glaucoma by mathematically analyzing the visual field data of primary open-angle glaucoma (POAG) without any assumption such as the retinal nerve fiber layer anatomy. METHODS: One hundred three visual fields of the 30-2 program of the Humphrey Field Analyzer obtained from 103 POAG patients of early to moderately advanced stage were included. Based on the interpoint correlation of deviation of the measured threshold value from the age-corrected normal reference value (total deviation, STATPAC), test points of the 30-2 program were mathematically clustered using the VARCLUS procedure, a new clustering algorithm developed by the SAS Institute. The sector value, which summarizes the visual field performance of the clustered test points (sector), also was calculated. RESULTS: The 30 degrees central visual field was divided into 15 sectors consisting of at least 3 points. The distribution of sectors was compatible with the projection of nerve fiber layers. There was no sector extending over the horizontal meridian, but the sector pattern was not completely symmetrical around it. Linear regression analysis of the sector values against the mean deviation (STATPAC) suggested that the index is useful in following visual field performance of each sector. CONCLUSION: The sector pattern and sector values obtained were considered useful in studying the visual field data of glaucoma. PMID- 8433831 TI - Bibliographies and abstracts. PMID- 8433832 TI - Effect of intermittent versus continuous patient monitoring on reliability indices during automated perimetry. AB - PURPOSE: This prospective, randomized study was undertaken to determine the effect of intermittent versus continuous patient monitoring on reliability indices (fixation losses, false-positive errors, and false-negative errors) during automated static perimetry. METHODS: A practice Humphrey Program C30-2 visual field was administered to 169 subjects (mean age +/- standard deviation, 56 +/- 18 years) for 1.5 minutes, during which time trained technicians continuously monitored all subjects and assessed patient fixation as noted on the eye monitor. The computer-generated reliability indices during the 1.5 minute practice test were recorded. After completion of the practice test, the 169 eyes were randomized to either intermittent or continuous monitor for the permanent C30-2 test. During intermittent monitoring, the technician returned periodically to the examination room to assess the subject's performance. For continuous monitoring, the technician continually assessed the subject's performance while remaining in the examination room throughout the test duration. RESULTS: The mean number of visits per visual field test during intermittent monitoring was 4.0, and mean test duration was 15.8 minutes. There was no difference in the mean deviation, pattern standard deviation, and short-term fluctuation (P = 0.85, 0.98, and 0.41, respectively) of the visual fields for intermittent and continuous monitoring, suggesting similar diffuse depression and localized defects in the visual fields for each group. The mean fixation losses (6.9%), false-positive errors (1.8%), and false-negative errors (5.8%) for the intermittently monitored group were not different from the mean fixation losses (7.8%), false-positive errors, (3.1%) and false-negative errors (5.0%) for the continuously monitored group (P = 0.40, 0.24, and 0.36, respectively). CONCLUSION: Although recommended, continuous monitoring does not appear necessary for all patients undergoing automated perimetry. Error-free reliability indices combined with the technician's judgment of patient reliability during the first 1.5 minutes of C30-2 testing may be a guideline for choosing intermittent monitoring. PMID- 8433833 TI - Prevention of early hypotony associated with Molteno implants by a new occluding stent technique. AB - BACKGROUND: A major complication of unvalved drainage tube implants is hypotony. Occluding stents to internally block the tube, but which lie exposed in the inferior fornix, have been described. The authors report modifications of this technique. METHODS: A nonexposed 3-0 Supramid suture is used to internally block the tube, with the end placed subconjunctivally. Small venting slits are made in the extrascleral portion of the tube to provide early control of intraocular pressure. Molteno implants were placed in 32 eyes of 29 patients using these modifications. RESULTS: Mean preoperative intraocular pressure was 30.3 mmHg on an average of 2.6 medications. The stent was pulled without difficulty in the office treatment room a mean of 26 days postoperatively. Intraocular pressure from postoperative day 2 until the day of stent removal ranged from 2 to 26 mmHg, with 72% of eyes having intraocular pressure between 5 and 19 mmHg. There were 3 (9.4%) minor complications in the 32 eyes, with 1 case of early anterior chamber shallowing and 2 cases of moderate choroidal detachments, which settled spontaneously. With an average follow-up of 10.2 months, mean intraocular pressure at the final visit was 13.4 mmHg on an average of 1 medication. CONCLUSION: The "occluding stent" described here can be a helpful adjunct to unvalved drainage tube surgery in preventing early postoperative hypotony. PMID- 8433834 TI - Food and Drug Administration study update. One-year results from 671 patients with the 3M multifocal intraocular lens. AB - PURPOSE/BACKGROUND: The clinical evaluation of the Food and Drug Administration study of the 3M diffractive multifocal intraocular lens (IOL) is presented here to demonstrate the results of 1-year postoperative data accumulated for 671 patients, the first of whom received the implant in 1987. METHODS: Patients were selected for study if they had absence of preoperative pathology, were at least 60 years of age, and had a reasonable postoperative prognosis. Extensive evaluations took place at 4 to 6 months and 12 to 14 months after surgery, including five different visual acuity measurements and contrast sensitivity. All testing was completed on both eyes. Data from the fellow eye served as a control when implanted with a monofocal IOL. RESULTS: Overall uncorrected distance visual acuity at 1 year after surgery shows 57% patients with 20/40 or better acuity. In this same group, 78% achieved J3 or better near vision, which improved to 82% in the best case group. Uncorrected visual acuity of 20/40 or better and J3 or better was achieved by 50% of best case multifocal IOL patients, compared with 26% of the monofocal best case comparison group. Measurements of contrast sensitivity consistently document a small loss, which is considered clinically insignificant. Statistical analysis of satisfaction ratings shows that predictors of satisfaction include uncorrected distance acuity, final near acuity, and fellow eye spherical equivalent. CONCLUSION: This multifocal lens appears to work very well for most patients, with more than half having functional uncorrected distance and near vision. The study showed several considerations that are important for optimizing clinical performance and patient satisfaction: patient selection, realistic expectations, accurate biometry, and adequate control of surgical procedures. PMID- 8433835 TI - Cell-mediated immunity in trachomatous scarring. Evidence from a leprosy population. AB - BACKGROUND: There is limited understanding of the mechanisms that mediate immunity after infection by Chlamydia trachomatis. Since it is known that the clinical course of leprosy is related to cell-mediated immunity and that such immunity contributes to the development of trachomatous conjunctival scarring, the authors examined patients to determine if there might be an association between leprosy status and trachomatous conjunctival scarring. METHODS: Leprosy patients registered at Shashemane Hospital were interviewed, examined, and patients with siblings residing in the vicinity were asked to return for further clinical examination. A subsample of sibships was selected for laboratory evaluation of cell-mediated immunity, measured by lymphocyte proliferative responses in vitro to stimulation by mycobacterial antigens. RESULTS: Conjunctival scarring was less severe in multibacillary leprosy patients (with suppressed cell-mediated immunity) than in their healthy siblings and more severe in paucibacillary leprosy patients (with enhanced cell-mediated immunity) than in their healthy siblings. The mean lymphocyte proliferative responses to mycobacterial antigens were greater in the sibling (whether leprous or healthy) with more severe conjunctival scarring, regardless of type of leprosy. CONCLUSION: The specific cellular immune responses to Mycobacterium leprae and p65 antigen in patients with increased conjunctival scarring provide evidence that early in the course of infection with C. trachomatis, factors related to an individual's cellular response are crucial to the development of conjunctival scarring. A delayed-type hypersensitivity reaction ("reversal reaction") found in paucibacillary leprosy patients could contribute to the increased trachomatous conjunctival scarring in these patients. PMID- 8433836 TI - Responses of Bacillus subtilis spores to space environment: results from experiments in space. AB - Onboard of several spacecrafts (Apollo 16, Spacelab 1, LDEF), spores of Bacillus subtilis were exposed to selected parameters of space, such as space vacuum, different spectral ranges of solar UV-radiation and cosmic rays, applied separately or in combination, and we have studied their survival and genetic changes after retrieval. The spores survive extended periods of time in space--up to several years--, if protected against the high influx of solar UV-radiation. Water desorption caused by the space vacuum leads to structural changes of the DNA; the consequences are an increased mutation frequency and altered photobiological properties of the spores. UV-effects, such as killing and mutagenesis, are augmented, if the spores are in space vacuum during irradiation. Vacuum-specific photoproducts which are different from the 'spore photoproduct' may cause the synergistic response of spores to the simultaneous action of UV and vacuum. The experiments provide an experimental test of certain steps of the panspermia hypothesis. PMID- 8433837 TI - Effects of solar radiation on the skin. AB - Solar ultraviolet radiation produces profound changes in human skin. Acute exposure results in inflammatory erythema, injury-response pigmentation, and immunologic alterations. Chronic exposure is responsible for deleterious changes in cutaneous structure and function as well as for neogenesis of the most common human malignancies. PMID- 8433838 TI - Genetic syndromes associated with skin cancer. AB - Most skin cancers are amenable to cure with early diagnosis and appropriate treatment; however, skin cancers associated with genetic syndromes may give rise to some of the most relentless, deforming, and ultimately lethal skin cancers clinicians will ever encounter. This article reviews the commonly accepted genetic syndromes associated with skin cancer, details their clinical pictures and key points of recognition and diagnosis, considers associated relevant clinical concerns, and discusses therapeutic options and dangers. PMID- 8433839 TI - Sunscreens and photoprotection. AB - This article discusses various forms of photoprotection. Mechanisms of action of chemical sunscreens, determination of sunscreen effectiveness, and adverse effects are detailed. Attention is also given to alternative methods of photoprotection and special recommendations for children. PMID- 8433840 TI - Actinic keratosis. A premalignant skin lesion. AB - The actinic keratotic lesion appearing on the sun-exposed skin of the middle-aged and elderly is a common premalignant lesion that infrequently becomes squamous cell carcinoma. Generally, superficially destructive measures provide adequate therapy for this epidermal dysplastic growth. Because of the rare threat of squamous cell carcinoma, a therapeutic dilemma results. If the physician detects any signs of malignancy, such as palpability, induration, or bleeding, a biopsy is mandatory for confirmation. PMID- 8433841 TI - Differentiation of basal cell carcinoma. AB - Basal cell carcinoma is undoubtedly the most common malignancy in light-skinned people. Because of the high incidence of this type of carcinoma, physicians should be familiar with its many clinical presentations. An understanding of the behavior, multiple histologic variations, and available therapeutic modalities is of great value in the diagnosis and treatment of this tumor. PMID- 8433842 TI - Cutaneous squamous carcinoma and related lesions. AB - The epidemiologic, etiologic, and prognostic factors in cutaneous squamous carcinoma depend heavily upon the status of the immune systems of the skin and body. Because UV radiation is both mutagenic and immunosuppressive, exposure to it will ultimately set the stage for the development of cutaneous carcinoma. If other immunobiologic-altering factors are added to UV radiation exposure, then both a susceptibility to invasion by oncogenic viruses and the development of squamous cell disorders, including squamous cell carcinoma, will exist. Although these factors are not totally controllable, a better understanding of them will allow the physician to more effectively tailor preventive care, treatment decisions, and counseling advice. PMID- 8433843 TI - Malignant melanoma of the head and neck. AB - The incidence of cutaneous malignant melanoma is increasing in the United States and throughout the world at an alarmingly rapid rate. Melanoma, however, is a highly curable cancer when diagnosed and treated appropriately at an early stage. This article provides current information about the epidemiology, risk factors, and the principles as well as the controversies associated with the diagnostic evaluation and treatment of patients with this neoplasia. PMID- 8433845 TI - Celebrate leadership 1903-1993. PMID- 8433844 TI - Adnexal carcinomas of the skin. AB - Adnexal carcinomas of the skin are a rare, highly malignant, and extremely diverse group of neoplasms. This article reviews skin adnexal tumors of nervous, vascular, and fibrous tissue of the head and neck. These tumors pose a significant diagnostic and therapeutic challenge, requiring close cooperation between the head and neck surgeon and the dermatopathologist. PMID- 8433846 TI - Autonomy for nursing education threatened. PMID- 8433847 TI - Your life, your health. The greatest love all--teach your children to value themselves. PMID- 8433848 TI - Gentle nursing massage. PMID- 8433849 TI - Who gets the kids if I die? PMID- 8433850 TI - IgE and protective immunity to helminth infections. PMID- 8433851 TI - The role of reactive nitrogen intermediates in modulation of gametocyte infectivity of rodent malaria parasites. AB - Direct feeding of Anopheles stephensi mosquitoes on mice infected with Plasmodium vinckei petteri showed that, during the periods of schizogony in the blood, the infectivity of gametocytes was markedly reduced. This could be prevented by prior injection of the L-arginine analogue, Nw-nitro-L-arginine (NwNLA) showing that the altered infectivity was due to reactive nitrogen intermediates (RNI). Similar effects on transmission of P. yoelii nigeriensis were demonstrated in vitro by membrane feeding of the mosquitoes. The in vitro reduction in infectivity could be reversed by injecting the L-arginine analogue either into the infected mouse donor of serum, or into the membrane feeding chamber. Elevated levels of TNF and IL-6 were demonstrated during the course of infection but did not correlate well with nitrogen radical activity. Similarly, direct measurements of NO2- and NO3- did not reflect the nitrogen radical activity revealed by addition of the specific L-arginine analogue. PMID- 8433852 TI - The detection of autoantibodies to IgE in plasma of individuals infected with hookworm (Necator americanus) and the demonstration of a predominant IgG1 anti IgE autoantibody response. AB - In this study we have demonstrated significantly elevated levels of circulating IgG autoanti-IgE antibody in hookworm infected individuals from Kebasob village on Karkar Island, Papua New Guinea. Although anti-IgE activity was demonstrable in IgG1, IgG3 and IgG4, IgG1 was by far the most important subclass of IgG anti IgE in terms of frequency of detection (34/39; 87.2%) and magnitude of increase (P = 0.0000); with IgG3 (16/39; 41.0%) and IgG4 (15/39; 38.5%) antibodies being considerably less prevalent. Plasma levels of IgG1 anti-IgE (P = 0.0019) and IgG3 anti-IgE (P = 0.0034) showed significant correlations with total IgE concentrations, but not with IgE specific to excretory-secretory worm products; thus suggesting that anti-IgE synthesis is more related to polyclonal hyper IgE production than to antigen-specific IgE stimulation. No correlation was seen between IgG subclass anti-IgE levels and faecal egg counts or worm burden. Given that our data failed to show a negative or a positive correlation between anti IgE and the degree of infection with hookworm, it is tempting to speculate that the main role of autoanti-IgE is to provide the host with protection against immune complex- and IgE-mediated hypersensitivity reactions to parasitic antigens. PMID- 8433853 TI - Immunity to helminths: is too much IgE parasite--rather than host-protective? PMID- 8433854 TI - Effect of group B streptococcal sepsis on diaphragmatic function in young piglets. AB - Recent studies indicate that diaphragmatic pressure generation (Pdi) is impaired by bacterial infection. However, group B streptococcus (GBS) had no effect on Pdi when infused into 4-wk-old piglets. As responsiveness to GBS is age-dependent, we therefore studied the acute effect of GBS infusion on Pdi, using a younger, 2-wk old piglet model. Using trans-Pdi with phrenic nerve stimulation, we studied the effect of continuous GBS infusion in seven anesthetized, spontaneously breathing 2-wk-old piglets. Pdi was measured under baseline conditions (50% O2/50% N2) and at 1, 2, and 4 h of GBS infusion. GBS was infused at a rate which caused a doubling of the pulmonary artery pressure but which avoided hypotension or acidosis--both of which can decrease Pdi. In addition, the piglets were kept hyperoxic [PaO2 > 13.3 kPa (100 torr)], and no piglet with hypercapnia [PaCO2 > 8.7 kPa (65 torr)] was included, as hypoxia and hypercapnia can also cause respiratory muscle dysfunction. For the GBS group, diaphragmatic contractility declined significantly by 1 h at 30-, 50-, and 100-Hz stimulation frequency and, by 2 h, was significantly decreased at all frequencies. We conclude that 2-wk-old piglets, in contrast to 4-wk-old piglets, demonstrate a decline in Pdi during GBS infusion. These data demonstrate an age-related response to GBS in the piglet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433855 TI - In vitro comparison of multinucleated giant cell formation from human umbilical cord and adult peripheral blood mononuclear phagocytes. AB - The fetus and newborn infant are highly susceptible to infection by pathogens that are capable of intracellular survival. The invasion of these microbes usually stimulates a granulomatous host defense response in the fetus or neonate. Multinucleated giant cells (MGC) are the predominant cells composing the granuloma and represent the terminally differentiated state of activated macrophages. Because macrophages derived from human umbilical cord blood monocytes demonstrate some deficiencies in activated functions, we tested the ability of these cells to form MGC in vitro. Mononuclear cells from umbilical cord blood and adult peripheral blood were isolated and cultured for 7, 14, or 21 d before stimulation with phorbol myristate acetate (PMA), an agent known to stimulate MGC from mononuclear phagocytes in vitro. Spontaneous MGC formation occurred in both cord and adult blood mononuclear cell cultures by d 7 of incubation, although significantly fewer MGC formed in the cord blood cultures. PMA treatment of adult blood mononuclear cells resulted in a significant increase in MGC formation after 7, 14, or 21 d of culture, but PMA did not significantly increase MGC formation in cord blood cultures until 14 or 21 d of culture. Pretreatment of cord and adult blood mononuclear cells with 1,25-dihydroxyvitamin D3 inhibited PMA-induced MGC formation. However, when a purified population of cord blood, monocyte-derived macrophages were pretreated with 1,25 dihydroxyvitamin D3, PMA significantly increased MGC formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433856 TI - Diminished actin polymerization by neutrophils from newborn infants. AB - During the newborn period, abnormalities of neutrophil (PMN) function predispose infants to serious bacterial disease. Actin is a major contributor to PMN shape change and motile behavior. To determine the mechanism underlying defects in newborn granulocyte polarity and chemotaxis, we investigated actin polymerization by cord blood PMN from healthy term infants and adult controls. F-actin (filamentous) content was quantified in the resting state and after stimulation by fluorescence-activated cell-sorter analysis of nitrobenzoxadiazole-phallacidin stained cells. PMN from newborn infants demonstrated similar basal F-actin levels when compared with adults. N-formyl methionyl leucyl phenylalanine induced a marked increase in actin polymerization that was maximal at 30 s in both neonates and adults and that then declined slowly (depolymerization) over the following 10 min. However, the F-actin content of PMN from newborn infants was significantly diminished when compared with adults at 30 and 60 s after N-formyl methionyl leucyl phenylalanine stimulation (p < 0.05). Both the rate and dose response of N formyl methionyl leucyl phenylalanine-induced actin polymerization were similar for adult and neonatal PMN. PMN from newborn infants also demonstrated significantly diminished actin polymerization when compared with adults 60 s after stimulation with platelet-activating factor (p < 0.05). Decreased concentrations of F-actin may help explain the observed abnormalities of PMN polarity and chemotaxis in healthy newborn infants. PMID- 8433857 TI - In vitro effect of indomethacin on polymorphonuclear leukocyte function in preterm infants. AB - Random motility and chemotaxis of polymorphonuclear leukocytes (PMN) was evaluated after in vitro exposure to 0, 300, 600, and 900 ng/mL (0.84, 1.68, and 2.52 mumol/L) of indomethacin. PMN were obtained from cord blood of 22 preterm infants of less than 37 wk gestation. For comparison, PMN were obtained from cord blood of seven healthy full-term infants and from venous blood of 10 normal adults. In preterm infants, a significant decrease of random motility and chemotaxis of PMN was noted at all three drug concentrations; impairment of PMN function was dose dependent in the three groups (p < 0.0001), with the greatest effect seen at 900 ng/mL (2.52 mumol/L). Significant impairment of random motility was noted in full-term infants when compared with adults at all indomethacin concentrations and in chemotaxis at 300 and 600 ng/mL (0.84 and 1.68 mumol/L). The study indicates that indomethacin has an adverse effect on PMN random motility and chemotaxis, which is more pronounced in preterm infants. PMID- 8433858 TI - Evolution of sequence divergence among human immunodeficiency virus type 1 isolates derived from a blood donor and a recipient. AB - Four neonates who were infected with a single unit of blood from a human immunodeficiency virus-1 (HIV-1)-infected adult (patient 1) were studied. Two of the infected children (patients II and III) developed symptomatic HIV-1 disease and died within the first 3 y of life. One child (patient IV) died at 8 mo of age of clinical problems that may have been HIV-related. In contrast, one child (patient V) has remained asymptomatic for 7.5 y and has exhibited a very gradual decline in CD4+ cell number. A previous study had shown very limited sequence diversity of isolates from patients I, II, and III (McNearney T et al.: Proc Natl Acad Sci USA 87:1917-1921, 1990). The current study examined additional HIV-1 sequences encoding the principal neutralizing V3 loop of the surface envelope protein of isolates from patients I and V. Amplified sequences were obtained using the polymerase chain reaction from a cultured isolate and uncultured peripheral blood leukocytes, and nucleotide sequences were determined for 13 clones from patient I and 19 clones from patient V. Clones derived from the cultured isolate exhibited less predicted amino acid sequence diversity on average (0-5.2%) than did sequences from uncultured leukocytes (0-19.8% differences). All clones were more closely related to those from patients II and III (0-19.8% amino acid differences) than to other North American or European isolates (18.8-27.0% amino acid differences) or African isolates (41.0-48.0% amino acid differences). Substitutions occurred at sites predicted to modulate host cell tropism and proteolytic cleavage of the V3 loop.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433859 TI - Proteins associated with cardiac neural crest in the pharyngeal region of early chick embryos. AB - Normal septation and alignment of the outflow tract of the heart depends on ectomesenchymal cells derived from the cardiac neural crest. Removal of the premigratory cardiac neural crest results in a variety of cardiac anomalies. The sequence of events leading to these cardiac anomalies in the absence of the cardiac neural crest cell population is not fully understood. This study is the first in a series directed at understanding the role of the neural crest in cardiovascular development at the molecular level. We have begun by distinguishing proteins uniquely expressed by, or responding to the presence of, cardiac neural crest cells in the pharyngeal apparatus, as well as proteins that are seen in the absence of cardiac neural crest cells. Cardiac neural crest was removed by microcautery from stage 9 to 10 embryos. At stages 14, 18, and 21, the protein patterns in the pharyngeal regions of experimental and sham-operated embryos were compared using isoelectric focusing followed by SDS-polyacrylamide gel electrophoresis. Five proteins were found in sham-operated embryos at stages 14 and 18 that could not be seen in embryos with neural crest ablations. Four proteins were found in embryos with neural crest ablation at stages 14 and 18 that were not seen in sham-operated embryos. By stage 21, the protein patterns of both sham-operated and experimental embryos were identical. These results indicate that there may be a compensatory response to neural crest ablation as development proceeds. PMID- 8433860 TI - Haemophilus influenzae type B impairment of pial vessel autoregulation in rats. AB - To examine the mechanisms of autoregulatory impairment in meningitis, we studied the effects of Haemophilus influenzae type b (Hib) on pial vessels during hemorrhagic hypotension in rats, using a cranial window technique. We prepared cranial windows in barbiturate-anesthetized, mechanically ventilated rats. Artificial cerebrospinal fluid or 10(5) Hib in cerebrospinal fluid (n = 7 each group) was suffused over the pial surface. Pial arteriolar diameter was measured hourly for 4 h. Autoregulation was assessed as the ability of pial arterioles to dilate in response to graded hemorrhagic hypotension at 2 and 4 h. Pial arterioles exposed to Hib dilated progressively to 149 +/- 27% of baseline at 4 h. Vessel diameter in the Hib group was significantly greater than in the control group beginning at 2 h. Autoregulation was progressively impaired in Hib-exposed rats compared with control rats [-5.85 +/- 1.38 versus -8.02 +/- 2.02 and -3.82 +/- 1.57 versus -8.53 +/- 1.72% dilation/kPa fall in mean arterial blood pressure at 2 and 4 h, respectively (p < 0.05)]. These data suggest that autoregulation is impaired in pial arterioles exposed to Hib because involved vessels have a finite dilatory capacity and are close to maximal dilation before hypotensive challenge. PMID- 8433861 TI - Estimation of cerebral venous saturation in newborn infants by near infrared spectroscopy. AB - The purpose of the study was to evaluate the near infrared spectroscopy technique for determination of the cerebral venous oxygen saturation. By tilting the patient's head down 15 degrees, changes in OD may be caused by changes in cerebral blood volume. On the assumption that increases in cerebral blood volume consist of venous blood only, cerebral venous oxygen saturation can be calculated as the measured change in oxygenated Hb divided by the change in total Hb. Two groups of mechanically ventilated, newborn infants were investigated: 10 asphyxiated, term infants and another 22 preterm infants with respiratory distress syndrome. All were monitored by near infrared spectroscopy during tilting, and cerebral blood flow was estimated by the 133Xe clearance technique immediately before tilting. Cerebral venous oxygen saturation could not be calculated in 13 preterm infants, as the blood volume remained constant during tilting. In the remaining 19, cerebral venous oxygen saturation averaged 0.67 (SD = 0.09) in asphyxiated infants and 0.53 (SD = 0.15) in preterm infants (p = 0.03). The corresponding values of cerebral blood flow were closely and inversely related to oxygen extraction calculated from cerebral venous saturation as estimated by near infrared spectroscopy. PMID- 8433862 TI - Comparison between near infrared spectroscopy and 133Xenon clearance for estimation of cerebral blood flow in critically ill preterm infants. AB - Estimations of cerebral blood flow were performed by both near infrared spectroscopy and 133xenon clearance on 12 occasions in nine critically ill premature infants (26-29 gestational wk) who required mechanical ventilation and supplemental oxygen. For each study, one determination of cerebral blood flow by 133xenon was compared with the mean of two to five measurements by near infrared done within 1-19 (median 5) h. 133Xenon measurements ranged from 9.6-16.9 mL/100 g/min, and mean near infrared measurements ranged from 8.6-25.0 mL/100 g/min. There was a significant correlation between the two sets of measurements (r = 0.80, p < 0.001). The mean difference between the methods was 1.6 mL/100 g/min, and the 95% limits of agreement were -0.5-3.8 mL/100 g/min. This study showed that cerebral blood flow can be measured noninvasively in critically ill premature infants at the cotside by near infrared spectroscopy and by the 133xenon clearance technique. The methods give comparable results. PMID- 8433863 TI - Frequent episodes of brief ischemia sensitize the fetal sheep brain to neuronal loss and induce striatal injury. AB - We examined the neuronal consequences of repeated brief episodes of in utero cerebral hypoxia-ischemia. Chronically instrumented fetal sheep were subjected to three 10-min episodes of reversible cerebral ischemia, repeated at either 1-h (n = 8) or 5-h (n = 5) intervals. Four fetuses were subjected to a single 10-min of ischemia and 17 fetuses to a single 30-min of ischemia. Repeated insults altered the distribution of damage with relatively marked striatal injury compared with isolated episodes of ischemia (p < 0.01). Frequent insults were associated with greater neuronal loss (p < 0.01) and a failure to restore electrocorticographic activity and resolve cortical cytotoxic edema between insults. Intermittent cortical hyperexcitability developed after repeated insults irrespective of the interval between insults. These findings emphasize that repeated brief episodes of ischemia alter the distribution of damage and sensitize the fetal brain to neuronal injury, particularly if the episodes are frequent. Striatal damage may be a feature of multiple but not single insults. PMID- 8433864 TI - Lipogenesis from lactate in fetal rat brain during late gestation. AB - Much evidence suggests that lactate may play a relevant role as a metabolic substrate for the brain immediately after delivery. In this work, the rate of lactate, glucose, and 3-hydroxybutyrate incorporation into CO2, phospholipids, and sterols was studied in fetal rat brain slices during the last 3 d of gestation. Lactate was the best substrate for the brain during the late gestation, not only as a source of energy, but also as precursor of brain phospholipids and sterols. The rates of oxidation and lipogenesis from glucose and 3-hydroxybutyrate showed a progressive decrease during the late gestation (10 15% reduction on d 20.5, p < 0.05, and 22-33% on d 21.5, p < 0.01, for oxidation; 14-18% on d 20.5, p < 0.05, and 20-22% on d 21.5, p < 0.05, for lipogenesis), whereas lactate maintained its rate of utilization in the same circumstances. The main phospholipid synthesized throughout the late gestation was phosphatidylcholine. The synthesis of phosphatidylcholine and phosphatidylethanolamine from lactate, glucose, and 3-hydroxybutyrate decreased during late gestation. Under these circumstances, however, the rate of phosphatidylserine synthesis from glucose was unchanged; it decreased from 3 hydroxybutyrate and increased from lactate. The rate of desmosterol synthesis was about 3- to 4-fold higher than those of cholesterol and lanosterol. Our results suggest that the capacity of fetal brain for lactate utilization remains high during late gestation, but the capacities for the utilization of glucose and 3 hydroxybutyrate decrease until term. This may indicate that lactate is an important substrate for brain development during late gestation. PMID- 8433865 TI - Reversal of the adverse chronic effects of the unsaturated derivative of valproic acid--2-n-propyl-4-pentenoic acid--on ketogenesis and liver coenzyme A metabolism by a single injection of pantothenate, carnitine, and acetylcysteine in developing mice. AB - Like treatment with the parent compound valproic acid (VPA), acute and/or chronic treatment with the unsaturated derivative, 2-n-propyl-4-pentenoic acid (4-en VPA), decreased ketogenesis and lowered free CoA, acetyl CoA, and free carnitine levels in the livers of normal developing mice. Concomitantly, there were manifold increases in the content of medium-chain acyl CoA esters (4-en-VPA CoA and 4-en-VPA CoA metabolites). Acute cotreatment of 4-en-VPA-treated animals with pantothenate, carnitine, and acetylcysteine caused significant amelioration of these metabolic aberrations. In animals chronically treated with 4-en-VPA, a single injection of pantothenate, carnitine, and acetylcysteine returned the 4-en VPA-depressed levels of beta-hydroxybutyrate in plasma and free CoA and acetyl CoA in liver to normal. These findings support the hypothesis that VPA- and 4-en VPA-induced hepatic dysfunction is produced by CoA sequestration rather than by irreversible inhibition by alkylation of the enzymes of fatty acid beta-oxidation by reactive intermediates. The findings also support the important but little known role of carnitine in CoA metabolism--carnitine relieves the inhibition of pantothenate kinase, the rate-controlling first enzyme in the pathway of CoA synthesis by its product, free CoA, and by CoA esters. PMID- 8433866 TI - Magnetic resonance spectroscopy shows increased brain glutamine in ornithine carbamoyl transferase deficiency. AB - We have performed localized in vivo proton magnetic resonance spectroscopy on two females with ornithine carbamoyl transferase deficiency during episodes of acute hyperammonemic encephalopathy with focal neurologic abnormalities. Spectra obtained from 2 x 2 x 2 cm cubic volumes at relatively long (135-ms) echo times contain additional signals that are characteristic of glutamine and indicate that glutamine is present in very high concentrations in the brain. The findings are consistent with the hypothesis that intracerebral accumulation of glutamine contributes to the encephalopathy associated with hyperammonemia. In one of the children, spectra obtained after treatment showed a marked decrease in the glutamine signals. PMID- 8433867 TI - Role of lipid peroxidation in metalloporphyrin-mediated phototoxic reactions in neonatal rats. AB - Our group previously demonstrated dose-dependent mortality in neonatal rats treated with tin protoporphyrin and light. We hypothesize that lipid peroxidation may be responsible for the toxic effects of photosensitizing metalloporphyrins. Neonatal rat blood samples with or without metalloporphyrins (40 mM) were exposed to cool white light (20 microW/cm2/nm) for 30 min at 37 degrees C. In the in vivo model, neonatal rat pups were given injections of 40 mumol of either tin protoporphyrin (4 mM), zinc protoporphyrin/kg body weight, or saline and placed over cool white light. The control animals were similarly treated but kept in the dark. After 3 h, the animals were killed, and their tissues were analyzed for malondialdehyde, conjugated dienes, and disappearance of polyunsaturated fatty acids as indices of lipid peroxidation. In all cases, the known photosensitizer tin protoporphyrin was associated with increased conjugated dienes in the liver and disappearance of polyunsaturated fatty acids and increased malondialdehyde in the liver and brain when animals were exposed to light. Zinc protoporphyrin was not associated with increased lipid peroxidation in the light except in the case of blood in vitro where malondialdehyde levels increased. We conclude that lipid peroxidation plays a role in metalloporphyrin-mediated phototoxicity in neonatal rat tissues. PMID- 8433868 TI - Calcium kinetics in the hyperprostaglandin E syndrome. AB - Metabolic investigations, including the use of stable isotopes of calcium, were used to study calcium kinetics in three children with the hyperprostaglandin E syndrome. The studies were performed both during indomethacin treatment and in the absence of therapy. Off therapy, each child had hypercalciuria (mean urinary calcium excretion 0.478 mM/kg/d), hyperprostaglandinuria, and elevated serum calcitriol concentration. All had diminished bone density and were euparathyroid. Indomethacin treatment was associated with a marked reduction in serum calcitriol concentration, as well as decreased prostaglandin E excretion. Mean urinary calcium excretion fell to 0.135 mM/kg/d. The stable isotope studies defined two components to the hypercalciuria of this disease: an indomethacin-sensitive dietary contribution and a relatively indomethacin-resistant bone resorptive element. Bone densitometry confirmed the presence of the resorptive element by demonstrating skeletal demineralization. PMID- 8433869 TI - Transmembrane signaling and T-cell immunodeficiency. AB - Activation of T cells after ligation of the antigen-specific T-cell receptor initiates a cascade of metabolic and biochemical alterations that culminate in cell proliferation. The major changes include a series of phosphorylation reactions on numerous protein substrates, phosphatidylinositol hydrolysis, intracellular Ca2+ accumulation, gene activation, lymphokine receptor expression, and lymphokine secretion. Despite a great deal of work unraveling the structure of the T-cell receptor complex and the many biochemical events triggered by ligation of the T-cell receptor, the exact link between the various responses is not entirely defined. Nevertheless, abnormalities in any of these initial events may be presumed to have an impact on signal transduction, thereby resulting in a T-cell immunodeficiency. Such defects may be restricted to certain T-cell subsets or functions or represent more global defects. PMID- 8433870 TI - New and old immunodeficiencies. AB - Yesterday's immunodeficiencies emphasized the clinical and familial associations of the syndromes and date from the 1920s (ataxia-telangiectasia, chronic mucocutaneous candidiasis), the 1930s (Wiskott-Aldrich syndrome), skipping the 1940s, but blossoming in the 15-y period from 1950 to 1965. In this period, primary immunodeficiencies affecting all the major limbs of the immune system were first described (1950: severe combined immunodeficiency; 1952: X-linked agammaglobulinemia; 1957: chronic granulomatous disease; 1965: C2 deficiency). Today's immunodeficiencies, as detailed in Stiehm's Immunologic Disorders in Infants and Children (Edition 1, 1973; Edition 2, 1980; and Edition 3, 1989) emphasize the immunologic and genetic aspects of immunodeficiency. These increased from 43 syndromes in the 1973 edition (34 primary, nine secondary) to 94 syndromes in the 1989 edition (66 primary, 28 secondary). This means that about two primary and one secondary immunodeficiencies have been uncovered annually. Tomorrow's immunodeficiencies, to be covered in Edition 4, will include new clinical and immunologic observations and molecular and biochemical studies that characterize some unique immunodeficiencies. These include the following six groups of defects: 1) neutropenic syndromes with hypogammaglobulinemia, including the WHIM syndrome; 2) phenotypic genetic syndromes with immunodeficiency including Bloom's syndrome and Schimke's immuno-osseous dysplasia; 3) natural killer cell defects associated with a) other primary immunodeficiencies, b) other nonimmunologic illness, and c) primary natural killer defects; 4) T-cell membrane defects; 5) IL defects; and 6) miscellaneous phagocytic illnesses including periodontitis and the asplenia syndrome. PMID- 8433871 TI - Severe combined immunodeficiency with selective T-cell cytokine genes. AB - A 4-y-old female with severe combined immunodeficiency disease had normal numbers of T cells in her circulation and normal T-cell subsets. However, her T cells proliferated poorly to mitogens and did not proliferate to antigens or to anti CD3 MAb. IL-2 receptor expression was normal, but IL-2 synthesis was undetectable. The addition of recombinant IL-2 to a mitogen-stimulated culture resulted in normalization of the proliferative response. Northern blot analysis of total RNA derived from the patient's T cells revealed a weak or absent expression of mRNA coding for IL-2, IL-3, IL-4, and IL-5. In contrast, there were normal amounts of mRNA coding for granulocyte-macrophage colony-stimulating factor. Tumor necrosis factor and IL-6 production were also normal. Nuclear run on transcriptional assays revealed markedly decreased levels of newly initiated nuclear transcripts coding for IL-2, IL-3, IL-4, and IL-5 and normal levels of granulocyte-macrophage colony-stimulating factor transcripts in the patient relative to control lymphocytes. Gel retardation assays suggest that the NFAT-1 nuclear transcription complex is abnormal in this patient. These results indicate that the patient suffers from a defect that affects the transcription of multiple T-cell lymphokines and suggest that abnormalities affecting the production of T cell lymphokines may underlie some of the primary immunodeficiency diseases. PMID- 8433872 TI - Prenatal diagnosis and genetic analysis of X-linked immunodeficiency disorders. AB - Several congenital immunodeficiency diseases can exhibit X-linked inheritance, including agammaglobulinemia, severe combined immunodeficiency, Wiskott-Aldrich syndrome, X-linked lymphoproliferative syndrome, and X-linked hyper-IgM syndrome. To date, the gene defects causing each of these X-linked immunodeficiencies have not been identified, and the pathogenic mechanisms whereby mutations in these genes result in immunodeficiency are obscure. Although rare, all are associated with severe infections from early life and high morbidity and mortality. Regional localization of each of these gene defects on the X chromosome has made possible carrier detection and prenatal diagnosis by linkage with polymorphic X chromosome markers in pedigrees demonstrating clear X-linked recessive inheritance. However, without a positive family history, it may not be possible to distinguish clinically between X-linked and autosomal forms. As a partial solution to this problem, it has now been established that female carriers of X-linked agammaglobulinemia, X-severe combined immunodeficiency, and Wiskott-Aldrich syndrome can be identified by the pattern of X chromosome inactivation in cell lineages targeted by each gene defect. As more families are offered the opportunity to use carrier detection and prenatal diagnosis, their decisions will reflect not only their personal experience with affected children with immunodeficiency, but also the clinical advances in bone marrow transplantation and immunomodulation. PMID- 8433873 TI - Overview of biochemical abnormalities and molecular genetics of adenosine deaminase deficiency. AB - Approximately 20 years ago, Giblett and coworkers serendipitously discovered that in some patients with the syndrome of severe combined immunodeficiency, the disease is due to an inherited deficiency of the enzyme adenosine deaminase (ADA). This then led to the discovery that inherited deficiency of the next enzyme in the same pathway for purine salvage, purine nucleoside phosphorylase, results in a profound defect in cell-mediated immunity. These two disorders, sometimes termed "purinergic immunodeficiency disorders," were the first of the inherited immunodeficiency disorders in which the specific molecular basis was determined. Although both are rare diseases, they are of importance for several reasons. First, they are among the few inherited disorders of which some children can be cured by a single treatment; second, they are ideally suited for gene therapy; and third, the pathologic mechanisms can tell us more about the nature of the immune system and have already allowed development of chemotherapy for some malignancies of the immune system. Knowledge of the specific defects has also facilitated diagnosis, counseling of families, and development of new approaches to therapy. This article focuses on ADA deficiency, briefly reviews the clinical and biochemical findings to provide a background for the next two articles in this supplement issue, and details work in progress with respect to several aspects of the specific molecular defects in different patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433874 TI - Enzyme replacement therapy with polyethylene glycol-adenosine deaminase in adenosine deaminase deficiency: overview and case reports of three patients, including two now receiving gene therapy. AB - During the past 6 y, 29 adenosine deaminase (ADA)-deficient patients with combined immunodeficiency have been treated with polyethylene glycol (PEG) modified bovine ADA (PEG-ADA). We have monitored plasma ADA activity, metabolic effects of treatment, and the evolution of antibody to PEG-ADA in these patients, in collaboration with immunologists and clinicians in North America, Europe, and Australia, who have monitored immune function and clinical response to treatment. This article summarizes the current status of PEG-ADA therapy and provides recommendations for its use. Recovery of specific immune function during treatment with PEG-ADA is illustrated for three patients, who represent early, delayed, these patients have entered a trial of gene therapy, but continue to receive enzyme replacement. PMID- 8433875 TI - Development of gene therapy for immunodeficiency: adenosine deaminase deficiency. AB - Deficiency of adenosine deaminase (ADA) results in severe combined immunodeficiency. Clinical cure has been observed in several ADA-severe combined immunodeficiency patients after bone marrow transplantation in which only donor T cells were engrafted, suggesting that T-cell correction alone is sufficient for full immune reconstitution. Children without an HLA-matched donor have been treated with polyethylene glycol-ADA as enzyme replacement therapy, resulting in varying degrees of immunologic and clinical improvement. In September 1990, we began treating a 4-y-old girl with periodic infusions of autologous culture expanded T cells genetically corrected by insertion of a normal ADA gene using retroviral-mediated gene transfer with the LASN vector. After 2 y of polyethylene glycol-ADA treatment and before gene therapy, she continued to experience recurrent infections, was anergic and lymphopenic, and was deficient in isohemagglutinins. After seven infusions totaling 7 x 10(10) T cells, she has demonstrated a substantial increase in the number of circulating T cells (571/microL pre-gene therapy versus a mean of 1995/microL with gene therapy infusions every 6-8 wk) and the ADA activity in her peripheral blood T cells has increased > 10-fold. The increase in T-cell numbers and ADA activity has been associated with the development of positive delayed-type hypersensitivity skin tests, a significant increase in the level of isohemagglutinins, the regrowth of tonsils, and a decreased number of infectious illnesses. This improvement has persisted during suspension of treatment for more than 6 mo. A second patient treated since February 1991 has shown similar improvement in immune status.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433876 TI - Mechanisms controlling the human immunoglobulin E response: new directions in the therapy of allergic diseases. AB - The IgE response plays a critical role in the pathogenesis of human allergic diseases. A detailed understanding of the mechanisms underlying the regulation of IgE synthesis is thus important in the development of new treatments for allergic diseases. It is now well established that the induction of IgE synthesis in human B cells requires two signals. The first signal is delivered by IL-4, which induces Ig gene switching to the epsilon locus. The second signal can be delivered by a number of B-cell activators which, in combination with IL-4, cause the expression of productive epsilon mRNA transcripts and the synthesis of IgE protein. These second signals include contact-mediated signals delivered by T cells via cognate or noncognate interactions. Epstein-Barr virus infection, hydrocortisone, and MAb to the B-cell antigen CD40. Cytokines such as IL-5 and IL 6 significantly amplify IgE synthesis, whereas interferon gamma (IFN-gamma) inhibits IL-4-induced IgE synthesis. The production of cytokines is frequently compartmentalized to specific T-cell subsets: TH1, but not TH2, cells produce IL 2, IFN-gamma and lymphotoxin, whereas TH2 but not TH1 cells produce IL-4, IL-5, IL-6, and IL-10. These two T-cell subsets therefore produce cytokines that functionally antagonize each other, e.g. IFN-gamma inhibits proliferation of TH2 cells. Recent studies indicate that severe allergic diseases such as atopic dermatitis are associated with expansion of TH2 cells. These observations provide a rationale for the use of agents that interfere with IL-4 production or action, or alternatively, the use of IFN-gamma in the treatment of severe allergic diseases. PMID- 8433877 TI - Features of human immunodeficiency virus infection and disease. AB - Characteristics of human immunodeficiency virus (HIV) strains and the host immune response against the virus are major determinants in the pathogenesis of AIDS. HIV isolates can be distinguished by their ability to infect and replicate to high titers in cells, to kill those cells, and to down-modulate the CD4 protein on the cell surface. In addition, their sensitivity to serum neutralization or enhancement of infection can be appreciated. The genetic sequences associated with these biologic and serologic properties have been localized and could eventually be helpful for antiviral therapy. These variations in properties of HIV strains appear to correlate with induction of neurologic and gastrointestinal disease by certain strains. In some cases, HIV can establish a silent, latent infection. The mechanisms involved are not well defined, but one concept involves the nef gene, which with some strains, can suppress virus replication. An important finding is that viruses recovered from individuals as they advance to disease have many properties in vitro of presumed virulence in the host, such as a wide cellular host range, cytopathicity, and resistance to the antiviral effect of Nef. The host immune response can control virus spread through antiviral antibodies or cellular immune responses. Neutralizing antibodies are not commonly found in infected individuals, suggesting that viruses "escape" this immune response. Instead, in some symptomatic patients, antibodies that enhance virus infection can be detected. The difference in sensitivity of a virus appears related to its envelope proteins. Cellular immune responses offer some promise in maintaining or eliminating virus infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433878 TI - Abnormalities of immune regulation in human immunodeficiency virus infection. AB - The severe depletion of CD4+ T cells is the most obvious and dramatic immunologic event that occurs in individuals infected with the human immunodeficiency virus (HIV) type 1 during development to AIDS. Nevertheless, a complex and sequential pattern of loss of T-helper cell (TH) function can occur years before development of AIDS symptoms. Such suppression could be due to immunosuppressive factors that are either products of HIV, such as gp120 and tat, or HIV-induced immunoregulatory cytokines such as transforming growth factor-beta and IL-10. Recent data suggest that multiple and independent immunosuppressive factors, including gp120-induced suppression and IL-10, are responsible for the loss of TH function seen in HIV-infected individuals before development of symptoms. The same TH functional abnormalities observed in adult patients are also seen in pediatric cases. Pediatric cases of HIV infection present some unique problems, however, in that one needs to be able to distinguish between HIV-induced suppression of TH function and the absence of TH function that is due to lack of maturation or immunologic priming. PMID- 8433879 TI - Maternofetal transmission of human immunodeficiency virus-1: the role of antibodies to the V3 primary neutralizing domain. AB - The increase in the number of human immunodeficiency virus-1 (HIV-1)-infected children is a direct consequence of the heterosexual spread of the disease to women and the growing number of HIV-positive i.v. drug users. It is not known how the majority of infants born to HIV-1-infected women escape HIV-1 infection, and, for those infected, the timing of HIV-1 transmission has yet to be determined. In addition, the role of maternal antibodies in the prevention of HIV-1 transmission to the fetus is unclear. We have previously demonstrated a correlation between vertical transmission and the absence of high-affinity/avidity antibodies to a peptide, KRI-HIGPGRAFYT, which corresponds to a region of the primary neutralizing domain of the gp120 V3 loop of HIVMN (MN-PND). The present study examines the correlation between the presence of these high affinity antibodies in women completing a pregnancy or undergoing an elective abortion and the detection of HIV-1 infection in their aborted fetuses. In several instances, transmission occurred despite high-affinity antibodies to the MN-PND. We have, therefore, evaluated the reactivity of sera to different MN-PND variants. In one infant born to a mother with high-affinity/avidity antibodies to KRI-HIGPGRAFYT (classic MN-PND), the infected baby developed antibodies to an MN-PND variant peptide against which his mother did not mount a humoral immune response during pregnancy. This finding indicates that fetal infection with MN-PND escape mutants arising during pregnancy may occur during a period when the mother is serologically negative. PMID- 8433880 TI - Intravenous immune globulin for the prevention of infections in children with symptomatic human immunodeficiency virus infection. AB - Infection with human immunodeficiency virus (HIV) causes a progressive immunodeficiency, often manifested in adults by the development of infections with relatively rare, opportunistic organisms. However, in HIV-infected children, recurrent serious infections with common encapsulated bacteria, as well as recurrent minor bacterial and viral infections, may be early and frequent manifestations of HIV disease. The use of i.v. immune globulin (IVIG) has been shown to prevent infections in patients with primary immunodeficiency and in uncontrolled studies of HIV-infected children. This article reviews the problem of and immunologic predisposition for recurrent infections in pediatric HIV infection and reports on the use of IVIG for prophylaxis. Updated analysis from the National Institute of Child Health and Human Development IVIG Clinical Trial, a multicenter, double-blind, placebo-controlled trial of the safety and efficacy of IVIG for the prevention of infections in children with symptomatic HIV infection, is presented. Between March 1988 and January 1991, 376 children with clinical or immunologic evidence of HIV disease who were randomized to receive IVIG or albumin placebo were enrolled in this trial. In children with an entry CD4+ count of 200/mm3 or higher, IVIG significantly increased the time free from serious bacterial infections and significantly decreased the rates of minor bacterial infections and viral infections. PMID- 8433881 TI - Molecular dissection of lymphocyte signal transduction pathways. AB - The earliest biochemical changes in lymphocyte activation include the accumulation of phosphotyrosine-containing proteins. This accumulation, catalyzed by specific protein tyrosine kinases, is required for subsequent cell activation. Experimental manipulation of these protein tyrosine kinases results in improved or decreased transit through the activation sequence. Analysis of transgenic animals bearing altered kinase genes permits assembly of a model for signal transduction from the T-cell antigen receptor. PMID- 8433882 TI - Treatment of autoimmune neuromuscular diseases with high-dose intravenous immune globulin. AB - The majority of autoimmune neuromuscular diseases fall into three groups: 1) The autoimmune neuropathies, which include the acute inflammatory demyelinating polyneuropathy (Guillain-Barre syndrome), the chronic inflammatory demyelinating polyneuropathy, the paraproteinemic polyneuropathies, and the anti-GM1-associated motor neuropathies with conduction block; 2) the inflammatory myopathies, which include the dermatomyositis and polymyositis complex; and 3) the autoimmune neuromuscular junction defects, which include myasthenia gravis, and the Lambert Eaton myasthenic syndrome. Laboratory and clinical evidence suggests that circulating antibodies or sensitized lymphocytes are operating in the pathogenesis of these conditions. Current immunotherapies include treatment with plasmapheresis, high-dose steroids, or immunosuppressive drugs. Although all of these therapies are effective in a number of patients and for some period of time, they often result in serious side effects that necessitate their discontinuation. The need for safer and more effective therapies in the treatment of these conditions prompted the use of high-dose i.v. immune globulin (IVIG). A number of small trials and a few reports suggest that IVIG is safe and effective in the treatment of patients with autoimmune neuropathies, inflammatory myopathies, and myasthenia gravis unresponsive to conventional therapies. We will present current experience with IVIG in the above-mentioned autoimmune neuromuscular diseases, and we will stress the need for long-term controlled studies. The possible immunomodulatory action of IVIG in these conditions will also be discussed. PMID- 8433883 TI - Decreased glucose oxidation in preterm infants fed a formula containing medium chain triglycerides. AB - Several formulas for preterm infants contain medium-chain triglycerides (MCT) to enhance fat absorption. Although fat absorption with MCT was slightly higher in several studies in preterm infants, a beneficial effect on growth has only been reported in one publication. We hypothesized that when part of the fat blend of preterm formula is substituted by MCT oil, this might lead to a different metabolic pattern in which, due to the preferential oxidation of MCT, an increase in lipogenesis from glucose could lead to an increase in metabolic rate. To study the impact of MCT on glucose metabolism, 18 preterm infants were randomized to receive either an MCT or an LCT formula containing 38- and 6%-by-weight medium chain fatty acids, respectively, in their fat blend. At 4 wk of age, the metabolic rate, substrate utilization, glucose kinetics, and oxidation were measured by indirect respiratory calorimetry in combination with a constant-rate oral infusion of [U-13C]glucose. The "true" rate of appearance of glucose (Ra "true") was measured from the dilution of the uniformly labeled (m + 6) species of infused tracer, whereas "apparent" rate of appearance of glucose (Ra "apparent") was measured from the dilution of infused tracer C (carbon). The latter was measured by an on-line combustion method using a gas chromatograph isotope ratio mass spectrometer. At a carbohydrate intake of 8.4 mg.kg-1.min-1, total utilization of carbohydrate was equal in both groups at 7.6 mg.kg-1.min 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433885 TI - Effect of the quality of infused energy on substrate utilization in the newborn receiving total parenteral nutrition. AB - Newborn infants (n = 26), subdivided into three groups in which only the nonprotein energy was manipulated, were studied during continuously administered total parenteral nutrition. Nonprotein energy intake was provided as a glucose/fat mixture, and fat energy represented 18% (group A), 29% (group B), and 40% (group C). Energy expenditure and substrate utilization were measured by indirect calorimetry during a 6-h period. Other analyses included 24-h urinary nitrogen excretion, glycemia, and lipid profile. The results showed that glucose oxidation increased with increasing total glucose intake (p < 0.05). Net fat oxidation was observed in all groups and increased with increasing percentage of energy infused as fat. The maximal oxidative glucose disposal rate observed was in group A (11.2 g/kg/d). Maximal fat oxidation observed was in group C (2 g/kg/d), in which energy delivered by fat represented 40%. This group was more energy efficient than the others. Oxygen consumption was not affected by modification of the source of energy, but carbon dioxide production was higher in group A (p < 0.05), as was the nonprotein respiratory quotient (p < 0.05). Despite differences in carbon dioxide production, arterial capillary PCO2 was not affected and, together with the higher (p < 0.05) minute ventilation, suggests that adequate pulmonary compensation occurred during the low-fat regimen. Arterial capillary PO2 was lower during the high-fat regimen (p < 0.05). Protein oxidation was greater in group A (1.14 +/- 0.32 g/kg/d) than in group B (0.70 +/- 0.21 g/kg/d) or group C (0.78 +/- 0.28 g/kg/d).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433884 TI - Effect of intravenous amino acids on protein metabolism of preterm infants during the first three days of life. AB - Twenty-three preterm infants with respiratory distress syndrome (mean birth weight 1.07 kg, SD 0.24 kg) were randomly assigned to receive glucose alone or glucose with amino acids (1.5 g.kg-1.d-1) i.v. beginning on the 1st d of life. Blood ammonia and serum urea, CO2 content, sodium, potassium, chloride, and ionized calcium concentrations were normal and did not differ between treatment groups. Nitrogen balance was significantly greater in the group that received amino acids [88 (SD 54) versus -135 (SD 45) mg.kg-1.d-1]. In 12 infants (seven, glucose-only; five, glucose and amino acids), leucine kinetic studies were also performed on the 3rd d of life. These 12 infants received a 4-h primed constant infusion of L-[1-13C]leucine. Blood and breath were collected and analyzed for [1 13C]ketoisocaproate and 13CO2, respectively. Leucine turnover and oxidation were calculated. Both leucine turnover and oxidation were significantly higher in the group receiving amino acids than in the glucose-only group [241 (SD 38) versus 164 (SD 25) mumol.kg-1.h-1 and 71 (SD 22) versus 40 (SD 17) mumol.kg-1.h-1, respectively]. In addition, the calculated rate of protein synthesis was higher in the group receiving amino acids [6.9 (SD 1.1) versus 5.0 (SD 1.2) g.kg-1.d-1]. These data indicate that the i.v. administration of amino acids (1.5 g.kg-1.d-1) to ill preterm infants beginning on the 1st d of life improves whole-body protein balance as a result of increased protein synthesis. PMID- 8433886 TI - Alterations in intestinal uptake and compartmentalization of zinc in response to short-term dexamethasone therapy or excess dietary zinc in piglets. AB - Premature infants receive high dietary zinc and often glucocorticoids as a treatment for chronic lung disease. A piglet model was developed to investigate intestinal zinc transport and distribution of tissue zinc in response to treatment with short-term (5 d) glucocorticoid therapy or a high zinc diet. Piglets (13-15 d old; n = 21) were randomly allocated to: 1) dexamethasone (DEX) therapy (1.5 mg/kg intramuscularly twice a day), 2) high zinc diet (15.3 mmol/kg), or 3) control group (0.3 mmol dietary zinc/kg and saline intramuscularly twice a day). Pig weight, formula intake, urine volume, and blood glucose were monitored. At necropsy, tissue samples were obtained to measure zinc in plasma and zinc and metallothionein in liver and small intestinal mucosa. Velocity of zinc uptake by intestinal brush border membrane vesicles was measured using 65Zn tracer. Maximum uptake rate and Km for zinc uptake by brush border membrane vesicles were significantly greater (p < 0.05) in DEX compared with control and high zinc groups. DEX-treated piglets had a significantly lower (p < 0.05) zinc efflux rate across brush border membrane vesicles compared with that of the control. The high zinc group had a higher liver (p < 0.05) and mucosal (p < 0.05) zinc content and higher liver metallothionein concentration (p < 0.001) compared with the control and DEX groups. Weight gain over 5 d was not different among groups. Daily blood glucose was higher (p < 0.05) in DEX versus control and high zinc groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433887 TI - Catalytic activity of tetrahydrobiopterin in dihydropteridine reductase deficiency and indications for treatment. AB - It is now widely accepted that tetrahydrobiopterin (BH4), the natural cofactor of aromatic amino acid hydroxylases, in the absence of its regenerating enzyme dihydropteridine reductase (DHPR), will function only stoichiometrically in the phenylalanine (Phe) hydroxylating system. This has limited the use of pterin cofactor in diagnosis and treatment of patients suffering from inherited DHPR deficiency, one of the most common forms of hyperphenylalaninemia caused by BH4 deficiency. This is despite the observation of a dramatic fall in serum Phe concentration after BH4 loading in such patients. In this study, quantitation of this phenomenon was obtained by comparing the kinetics of serum Phe after either a simple Phe or a combined Phe plus BH4 oral loading in patients with Phe hydroxylase or with DHPR deficiency. Only in the latter was the total body clearance of Phe enhanced up to 5 times by the cofactor administration, resulting in the molar equivalent of Phe hydroxylated/mol of BH4 ranging from at least 6 to 10, against the postulated 1. As a consequence, BH4 administration should be attempted therapeutically in DHPR-deficient patients, thus avoiding a lifelong Phe-restricted diet. Preliminary experience with such treatment is given with two cases. PMID- 8433888 TI - Multiple acyl-coenzyme A dehydrogenation disorder responsive to riboflavin: substrate oxidation, flavin metabolism, and flavoenzyme activities in fibroblasts. AB - Multiple acyl-CoA dehydrogenation disorders result from generalized defects in intramitochondrial acyl-CoA dehydrogenation. Fibroblasts from a riboflavin responsive multiple acyl-CoA dehydrogenation disorder patient catabolized 14C butyrate, -octanoate, and -leucine normally after culture in riboflavin supplemented medium (2 mg/L). After culture in riboflavin-depleted medium (< or = 1.4 micrograms/L), his cells oxidized the same substrates poorly at 20 to 33% of control (p < 0.05). Patient cells incubated in a wide range of D-[2 14C]riboflavin concentrations (3, 31.4, and 100 micrograms/L) synthesized 14C flavin mononucleotide and 14C-flavin adenine dinucleotide (FAD) normally and had normal cytosolic 14C-flavin mononucleotide and 14C-FAD contents, which argues against defects in cellular riboflavin uptake and conversion to flavin mononucleotide and FAD. After culture in 31.4 micrograms 14C-riboflavin/L for 2 wk, 14C-FAD specific radioactivities plateaued and were similar in patient and control cells. However, culturing these uniformly labeled cells in riboflavin depleted medium for 2 wk lowered the patient's cellular 14C-FAD content to only 23% of control levels. Similarly, after incubation in low 14C-riboflavin concentrations (4.4 micrograms/L), the patient's mitochondrial 14C-FAD content was only 51% of control after 1 h and 29% of control at 4 h. After a 4-h incubation in a high physiologic concentration of 14C-riboflavin (31.4 micrograms/L), which raised the patient's cellular 14C-FAD levels 3- to 4-fold, his mitochondrial 14C-FAD content rose to normal; control values did not change. We also investigated possible defective FAD binding to flavoenzymes essential for acyl-CoA dehydrogenation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433889 TI - Developmental expression of vasopressin in the human hypothalamus: double labeling with in situ hybridization and immunocytochemistry. AB - The developmental expression of arginine vasopressin (VP) and VP mRNA in human hypothalamus was studied using combined immunocytochemistry (ICC) for VP neurophysin II and in situ hybridization (ISH) for VP mRNA. Routine formalin fixed autopsy material was used from 22 cases ranging in age from 18 wk of gestation to 21 yr. VP-neurophysin II immunoreactive cells were detected in the supraoptic, accessory supraoptic, and paraventricular nuclei of all brains examined. The average size of the immunocytochemically labeled cells increased until birth and remained constant thereafter. VP mRNA was first detected in cells at 21 wk gestation; 3 wk after the first detectable VP by ICC. After 27 wk of gestation, consistent and strong signals were obtained from the specimens that were double-labeled for both immunoreactive VP-neurophysin II and VP mRNA. Three populations of double-labeled cells were identified: type 1, intensely positive for both ISH and ICC (most magnocellular neurons); type 2, positive for ISH and weak or negative for ICC (rare and generally found in younger fetuses), and type 3, positive for ICC and weak or negative for ISH (mostly scattered in accessory nuclei). Thus, double-labeling techniques can be routinely used on frozen or paraffin sections of human autopsy material for the simultaneous assessment of both message and peptide. In the human fetus, the relatively late appearance of adult-like levels of VP mRNA in the magnocellular neuroendocrine cells suggests an association with the development of functional synaptic interactions in this system. PMID- 8433890 TI - Development of the sleep and wakefulness rhythm in preterm infants discharged from a neonatal care unit. AB - The purpose of this study was to investigate the effect of constant light in a neonatal care unit on the development of the sleep-and-wakefulness rhythm in preterm infants. Two groups of infants (57 preterm infants without other complications and 58 healthy term infants) were prospectively studied over infancy by a day-by-day plot method, by which sleep-and-wakefulness states were recorded at home for more than 14 d to compare developmental courses of the sleep and-wakefulness rhythm between the two groups at corrected and postnatal ages. In the two groups, there were no significant differences in distribution of emergence of periodicity of sleep states and wakeful states, total sleep time, nocturnal sleep time, diurnal sleep time, longest sustained sleep period, and longest sustained wakeful period at the same corrected ages. Moreover, the SD of the time of onset of the longest sustained sleep period of each subject diminished with increase in postconceptional weeks. The results suggest that the development of the sleep-and-wakefulness rhythm in preterm infants is not necessarily retarded if they are discharged from the neonatal care unit under constant light before an infant's innate biologic clock is mature enough to respond to an environmental cycle; rather it depends on their corrected ages. PMID- 8433891 TI - Negative regulation of antioxidant enzyme gene expression in the developing fetal rat lung by prenatal hormonal treatments. AB - Prenatal administration of thyrotropin-releasing hormone (TRH) or TRH plus dexamethasone (DEX) to pregnant rats accelerates lung surfactant system development in late gestation, but paradoxically depresses the normal late gestational elevation in fetal lung antioxidant enzyme (AOE) activities (Pediatr Res 30:522, 1991). In these present studies, we tested whether both prenatal hormonal treatments act to depress normal fetal lung AOE development by negative regulation of AOE gene expression. We used solution hybridization to quantitate the concentration of AOE mRNA. Results of the developmental studies revealed significantly decreased lung mRNA concentrations of copper-zinc superoxide dismutase, manganese superoxide dismutase, catalase, and glutathione peroxidase in late gestation as a result of prenatal TRH treatment. The addition of DEX administration did not reverse the lowered expression of lung AOE genes due to TRH treatment, but instead resulted in significant additional decreases in pulmonary AOE mRNA levels at both 21 and 22 d of gestation. The tested AOE mRNA half-lives (stabilities) revealed no significant differences between controls (8.0-10.5 h) and TRH-treated (8.2-9.5 h) and TRH-plus-DEX treatment (7.8-10.7 h) groups. These findings suggest that prenatal treatment with TRH and with TRH plus DEX acts to depress the normal late fetal lung AOE activity elevations by (direct) negative regulation of AOE gene expression, and the decreased AOE expression is likely regulated at the level of gene transcription rather than posttranscriptionally. PMID- 8433892 TI - Antioxidant enzyme responses to hyperoxia in preterm and term rats after prenatal dexamethasone administration. AB - Although prenatal steroid therapy is known to enhance in utero maturation of the surfactant and antioxidant enzyme systems, little is known about the effects of steroids on the antioxidant system after birth. We measured activities of the antioxidant enzymes, catalase, superoxide dismutase, and glutathione peroxidase, in lung homogenates from both preterm and term rat pups after prenatal dexamethasone treatment. Enzyme activities were measured at birth and after exposure to > 98% oxygen. Dexamethasone treatment resulted in significantly higher survival of the preterm pups at 24 h (91.3% for dexamethasone versus 57% for saline). In preterm pups, the activities of catalase and superoxide dismutase at birth were higher after dexamethasone treatment (p < 0.05). However, after 24 h of hyperoxic exposure, there were no differences in activities of any of the antioxidant enzymes between the dexamethasone and control groups of prematurely born pups. In term pups, antioxidant enzyme activities did not differ significantly at birth; nor did they differ after 24 to 72 h of hyperoxic exposure in the dexamethasone and control treatment groups. Our results indicate that although prenatal dexamethasone treatment augments survival and catalase and superoxide dismutase activities at birth in preterm rat pups, dexamethasone does not result in altered early postnatal antioxidant enzyme activities after exposure to hyperoxia. PMID- 8433893 TI - The effect of adenosine transport inhibition on cardiovascular function and survival after severe asphyxia in fetal lambs. AB - When the energy demand exceeds the energy supply, anaerobic metabolism takes over and the ATP catabolite adenosine is generated. Adenosine acts as a coronary vasodilator, thereby increasing the oxygen supply to the heart. Its potential, however, is poorly exploited due to extensive catabolism. R-75231 inhibits transport of adenosine into endothelial cells, where it is catabolized, resulting in an elevation of interstitial adenosine concentrations. In 14 fetal lambs (3 to 5 d after surgery, gestational age 124.1 +/- 1.1 d), seven fetuses were pretreated with R-75231 (0.1 mg/kg estimated fetal weight as a bolus injection in the inferior vena cava), whereas the other seven served as controls. After 1 h of severe asphyxia, induced by restriction of uterine blood flow, those fetuses treated with R-75231 showed a faster normalization of aortal pH and, in contrast to the control group, did not develop tachycardia. The percentage increase in myocardial blood flow during asphyxia, measured with radioactive microspheres, was significantly higher in the R-75231-treated group compared with the control group (437 and 284%, respectively). In the control group, only three fetuses recovered and survived, whereas in the R-75231 group, all seven animals recovered after severe asphyxia. It is concluded that fetal lambs pretreated with R-75231 before the onset of severe asphyxia have an enhanced increase in myocardial blood flow during asphyxia, recover faster, and survive longer. PMID- 8433894 TI - The circulatory effects of epinephrine infusion in the anesthesized piglet. AB - There are few published data regarding the circulatory effects of systemic epinephrine infusions in newborn subjects. We therefore instrumented six piglets aged 5 to 10 d while they were under pentobarbitone anesthesia for determination of cardiac output, left anterior descending coronary artery flow, systemic and pulmonary pressures, and mixed venous, arterial and coronary sinus gases. Systemic, coronary, and pulmonary vascular resistances, coronary oxygen consumption, and myocardial oxygen extraction ratio were calculated. Epinephrine was infused at doses from 0.2 to 3.2 micrograms/kg/min doubling at 15-min intervals, and measurements were taken after stability had been obtained. Cardiac output increased at the lowest dose investigated, i.e. 0.2 micrograms/kg/min, and progressively increased as the dose was advanced up to 1.6 micrograms/kg/min, decreasing significantly at 3.2 micrograms/kg/min. Blood pressure increased progressively, being significantly above baseline at 0.8, 1.6, and 3.2 micrograms/kg/min and having increased by approximately 81% at the highest dose investigated. Pulmonary arterial pressures were also increased at 1.6 and 3.2 micrograms/kg/min, but only by 35% at the highest dose of 3.2 micrograms/kg/min. Systemic and pulmonary vascular resistances both decreased at the three lower doses investigated and then began to increase progressively; however, the systemic vascular resistance increased to a significantly greater degree than pulmonary vascular resistance. Coronary oxygen consumption increased progressively as the epinephrine dose was increased; however, coronary blood flow and coronary oxygen delivery increased more than oxygen consumption, leading to a progressive reduction in myocardial oxygen extraction ratio and a progressive increase in coronary sinus oxygen content. Whole-body oxygen consumption was increased, but to a lesser extent than systemic oxygen transport.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433895 TI - Selection of metalloporphyrin heme oxygenase inhibitors based on potency and photoreactivity. AB - The heme oxygenase inhibitor, tin protoporphyrin, is being studied for the prevention of neonatal jaundice. This potential drug, however, is also a photosensitizer that could cause serious and unknown side effects when administered to newborns. Therefore, we have developed in vitro and in vivo procedures for the screening and further characterization of potentially safe heme oxygenase inhibitors. The ideal inhibitor: 1) contains a biocompatible metal, 2) is not degraded in tissues, 3) is a highly potent inhibitor of heme oxygenase, and 4) does not participate in photochemical reactions. Proto- and mesoporphyrin derivatives with the tin, zinc, manganese, chromium, nickel, and magnesium were screened in vitro for suitability. Chromium protoporphyrin and mesoporphyrin were further studied in vitro and in vivo and were found to meet the ideal criteria. Chromium mesoporphyrin appeared to be the most potent in vitro inhibitor of adult Wistar rat tissue heme oxygenase. Four mumol of chromium protoporphyrin or chromium mesoporphyrin/kg body weight, administered intraperitoneally to adult male Wistar rats given a heme load through intraperitoneal administration of 30 mumol heme/kg body weight, caused significant suppression of hemolysis-induced increase in carbon monoxide production to 72 and 44% of control, respectively, 5.5 h after treatment. At t = 6 h, the tissue heme oxygenase activity, measured in vitro, was significantly reduced to 33 and < 5% in liver and to 22 and < 5% in spleen after the administration of chromium protoporphyrin and mesoporphyrin, respectively, but was not reduced in brain. The results show that there exist effective metalloporphyrin heme oxygenase inhibitors without photosensitizing properties. PMID- 8433896 TI - Prenatal diagnosis of X-linked centronuclear myopathy by linkage analysis. AB - The X-linked recessive centronuclear/myotubular myopathy (XLR-CNM/MTM1), a severe neonatal disorder characterized by generalized hypotonia, muscle weakness, and primary asphyxia, has recently been mapped to Xq28. This report presents the first four prenatal diagnoses of XLR-CNM using DNA markers of the Xq28 region. The analyses of one female and three male fetuses revealed maternal transmission of the XLR-CNM-associated alleles in all four cases. Two of the male fetuses have been aborted, and the pregnancies of the third male and the female fetuses have been continued. The diagnosis of XLR-CNM at the birth of the third boy, as well as the pathologic findings in the muscle of one of the aborted fetuses, confirmed the linkage results of the prenatal analyses. Our findings prove the DNA markers St14, cpX67, DX13, and pSt35-691 to be useful in prenatal diagnosis of XLR-CNM and present the possibility to confirm the diagnosis by histologic examination of the first-trimester abortus. This permits an indirect prenatal diagnosis of XLR CNM in chorionic villus biopsies at 9 to 12 wk gestation, using DNA-based linkage analyses allowing early termination of an affected pregnancy. PMID- 8433897 TI - Interspecific plasmid transfer and modification of heat-stable enterotoxin expression by Klebsiella pneumoniae from infants with diarrhea. AB - We have previously described two heat-stable enterotoxins (ST) produced by Citrobacter freundii and by Klebsiella pneumoniae. To see whether transfer of toxigenic ability may occur between different bacterial species, conjugal mating experiments were performed using strains isolated from children. Donors and recipients were incubated together. ST production by the recipients was tested by the suckling mouse assay, which is the standard biologic method for detecting ST, and also by an ELISA test. The latter is based on MAb directed to Escherichia coli 18- or 19-amino acid toxin. Citrobacter and E. coli strains producing an ELISA-positive ST were used as plasmid donors. Recipients were E. coli, Klebsiella P89, and Klebsiella AL55. The latter had been previously shown to be capable of producing an ELISA-negative ST, but had spontaneously lost this ability. After conjugation, all strains gave positive results in the suckling mouse assay. However, E. coli and Klebsiella P89 ST were positive in the ELISA test, whereas Klebsiella AL55 ST was negative. The same three strains were transformed by inserting the plasmid pSLM004 encoding an ELISA-positive ST. Klebsiella P89 and E. coli became capable of producing an ELISA-positive ST, whereas Klebsiella AL55 cells were positive in the suckling mouse assay but negative in the ELISA. To assess whether the toxigenicity acquired was itself transmissible, the new ST-producing strains were incubated with a nontoxigenic Citrobacter strain. The latter became capable of producing an ELISA-positive ST in all cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8433898 TI - Glucose production rate in extremely immature neonates (< 28 weeks) studied by use of deuterated glucose. AB - Neonatal hypoglycemia is a frequent complication in immature infants. This may be due to small substrate stores, a high brain:body weight ratio, and immature enzyme systems. The purpose of the present study was to investigate the rate of glucose production in newborn infants with gestational ages of less than 28 wk. The subjects were 10 newborn infants delivered after 25 to 26 gestational wk. Their mean birth weight was 772 g (range 588-1000 g), and their mean postnatal age at the time of the study was 15 h (range 4-24 h). An isotopic compound (D-6,6 2H2-glucose) was given as a constant-rate i.v. infusion. In addition to dideuteroglucose, eight of the infants also received an i.v. infusion of unlabeled glucose at a rate of 1.4-2.6 mg.kg-1.min-1. Blood samples for determination of the concentration and isotopic enrichment of plasma glucose were obtained every 15 min in a 2-h period. Isotopic enrichment, measured by gas chromatography/mass spectrometry, was used for calculating the glucose production rate. The mean glucose production rate related to body weight (+/- SD) was 6.1 +/ 1.5 mg.kg-1.min-1. The results show that infants born at < 28 gestational wk have a capacity to produce glucose on their 1st d of life at rates close to or even exceeding those reported in term infants. PMID- 8433899 TI - Visual and somesthetic influences on postural orientation in the median plane. AB - We investigated optic and somesthetic contributions to perceived body orientation in the pitch dimension. In a within-subject factorial design, each of 12 subjects attempted to set his/her body erect or 45 degrees back from erect while restrained in a movable bed surrounded by an adjustable box. The box provided a visual environment consisting of either a grid pattern, two luminous lines, or complete darkness. Both the grid pattern and the luminous lines were effective at biasing settings of body position when the box was pitched; the pitched grid was more effective than the pitched lines. Although the pitch of the box influenced orientation to both goals, the effect was greater for the diagonal goal than for the erect goal. We present a model of postural orientation in the median plane that involves vestibular, somatosensory, and visual inputs. PMID- 8433900 TI - The object-line inferiority effect in pigeons. AB - Eight pigeons (Columba livia) were trained to discriminate between diagonal lines presented alone or embedded in a redundant L-shape right-angle form. The stimuli were white and were presented in an environment that was otherwise totally dark. Numerous experiments done with human observers have shown a strong superiority effect when the diagonal lines are embedded in redundant contexts. However, in Experiment 1 of the present study, the pigeons discriminated significantly better between the two diagonal lines when presented alone than when they were embedded in the right-angle context. In order to check on the possibility that these results were restricted to the semi-Ganzfeld condition of Experiment 1, a second experiment was done with black stimuli presented on a white background. Results of Experiment 2 also showed a strong distractor effect. The results of the present experiments confirmed the predictions of the Heinemann and Chase model of pattern recognition by pigeons. PMID- 8433901 TI - Modeling perceived relationships between melody, harmony, and key. AB - Perceptual relationships between four-voice harmonic sequences and single voices were examined in three experiments. In Experiment 1, listeners rated the extent to which single voices were musically consistent with harmonic sequences. When harmonic sequences did not change key, judgments were influenced by three sources of congruency: melody (whether the single voice was the same as the soprano voice of the harmonic sequence), chord progression (whether the single voice could be harmonized to give rise to the chord progression of the harmonic sequence), and key structure (whether or not the single voice implied modulation). When key changes occurred, sensitivity to sources of congruency was reduced. In Experiment 2, another interpretation of the results was examined: that consistency ratings were based on congruency in well-formedness. Listeners provided well-formedness ratings of the single voices and harmonic sequences. A multiple regression analysis suggested that consistency ratings were based not merely on well formedness but on congruency in melody, chord progression, and key structure. In Experiment 3, listeners rated the extent of modulation in harmonic sequences and in each voice of the sequences. Discrimination between modulation conditions was greater for single voices than for harmonic sequences, suggesting that abstraction of key from melody may occur without reference to implied harmony. A partially hierarchical system for processing melody, harmony, and key is proposed. PMID- 8433902 TI - Motion structure in five-dot patterns as a determinant of perceptual grouping. AB - The effect of basic motion structures on perceptual grouping was studied with five-dot motion patterns. Four basic motion structures were identified in terms of proximal common and relative motion vectors. In a forced-choice situation, the observers had to decide to which of two pairs of dots a fifth critical dot seemed to belong. Thus, one of two possible three-dot units was chosen by the observers. The two possible three-dot units defined different motion structures, and the chosen motion structure was considered to have stronger grouping power than the alternative structure had. It was found that parallel common motions (perceived translation in the plane) had the strongest grouping power; these were followed by circular common motions (perceived rotation in the plane), concurrent relative motions (perceived translation in depth), and, finally, parallel relative motions (perceived rotation in depth). The results also suggested effects of proximity and orientation of axis of rotation. It is further argued that the relative grouping power of the motion structures could not solely be interpreted in terms of changes of directions and distances between the dots. Instead it is suggested that vector analysis is a fundamental perceptual activity and that basic motion structures determine grouping power. PMID- 8433903 TI - Reproduction of musical rhythms by children, adult musicians, and adult nonmusicians. AB - Many sequential events, musical rhythms in particular, can be described by a hierarchical structure, with lower order events recursively combining to form higher levels. This study investigated factors influencing the ease of reproduction of short musical rhythms that reflect various organizational principles. For adults and children, reproduction was better for rhythms with the following characteristics: (1) binary rather than ternary subdivision, (2) two rather than three different durations, (3) the ability to be segmented into two shorter rhythms of identical duration, and (4) intensity accents on important hierarchical positions. These findings suggest that a prototypical temporal structure--that is, a regular beat with binary subdivisions--is functional in childhood. The ability to process complex hierarchical structure appeared to be influenced more by musical training than by passive acculturation. PMID- 8433904 TI - Context influence on the perception of figures as conditional upon perceptual organization strategies. AB - Two experiments tested the effect of context on figure perception. Subjects were shown rapid sequences of three figures: a prime, a whole, and a part. They were asked to decide if the third figure was a part of the second (Experiment 1) or if the second and third figures were the same or different with respect to a particular angle (Experiment 2). The prime served to establish a context for stimuli that followed to be compared. Priming had influence on the part-whole comparison in Experiment 1, but not on the local comparison in Experiment 2. The results of Experiment 1 were interpreted as evidence for a role of prior information in perceptual organization. Experiment 2 showed that the task must require an integrative perceptual organization strategy for the priming effects to occur. PMID- 8433905 TI - Tactile pattern recognition by graphic display: importance of 3-D information for haptic perception of familiar objects. AB - Haptic recognition of familiar objects by the early blind, the late blind, and the sighted was investigated with two-dimensional (2-D) and three-dimensional (3 D) stimuli produced by small tactor-pins. The 2-D stimulus was an outline of an object that was depicted by raising tactor-pins to 1.5 mm. The 3-D stimulus was a relief that was produced by raising the tactors up to 10 mm, corresponding to the height of the object. Mean recognition times for correct answers to the 3-D stimuli were faster than those for the 2-D stimuli, in all three subject groups. No statistically significant differences in percentage of correct responses between the 2-D and the 3-D stimuli were found for the late-blind and sighted groups, but the early-blind group demonstrated a significant difference. In addition, the haptic legibility for the quality of depiction of the object, without regard to whether or not the stimulus was understood, was measured. The haptic legibility of the 3-D stimuli was significantly higher than that of the 2 D stimuli for all the groups. These results suggest that 3-D presentation seems to promise a way to overcome the limitations of 2-D graphic display. PMID- 8433906 TI - Comparing decision bound and exemplar models of categorization. AB - The performance of a decision bound model of categorization (Ashby, 1992a; Ashby & Maddox, in press) is compared with the performance of two exemplar models. The first is the generalized context model (e.g., Nosofsky, 1986, 1992) and the second is a recently proposed deterministic exemplar model (Ashby & Maddox, in press), which contains the generalized context model as a special case. When the exemplars from each category were normally distributed and the optimal decision bound was linear, the deterministic exemplar model and the decision bound model provided roughly equivalent accounts of the data. When the optimal decision bound was non-linear, the decision bound model provided a more accurate account of the data than did either exemplar model. When applied to categorization data collected by Nosofsky (1986, 1989), in which the category exemplars are not normally distributed, the decision bound model provided excellent accounts of the data, in many cases significantly outperforming the exemplar models. The decision bound model was found to be especially successful when (1) single subject analyses were performed, (2) each subject was given relatively extensive training, and (3) the subject's performance was characterized by complex suboptimalities. These results support the hypothesis that the decision bound is of fundamental importance in predicting asymptotic categorization performance and that the decision bound models provide a viable alternative to the currently popular exemplar models of categorization. PMID- 8433907 TI - Shape from stereo: a systematic approach using quadratic surfaces. AB - We used quadratic shapes in several psychophysical shape-from-stereo tasks. The shapes were elegantly represented in a 2-D parameter space by the scale independent shape index and the scale-dependent curvedness. Using random-dot stereograms to depict the surfaces, we found that the shape of hyperbolic surfaces is slightly more difficult to recognize than the shape of elliptic surfaces. We found that curvedness (and indirectly, scale) has little or no influence on shape recognition. PMID- 8433908 TI - Vertical-horizontal illusion: one eye is better than two. AB - The vertical-horizontal illusion is the tendency for observers to overestimate the length of a vertical line relative to a horizontal line that has the same length. One explanation of this illusion is that the visual field is elongated in the horizontal direction, and that the vertical-horizontal illusion is a kind of framing effect (Kunnapas, 1957a, 1957b, 1957c). Since the monocular visual field is less asymmetric than the combined visual field, this theory predicts that the illusion should be reduced with monocular presentation. This prediction was tested in five experiments, in which the vertical-horizontal illusion was examined in a variety of situations--including observers seated upright versus reclined 90 degrees, monocular presentation with the dominant versus the nondominant eye, viewing in the dark versus in the light, and viewing with asymmetrical frames of reference. The illusion was reliably reduced with monocular presentation under conditions that affected the asymmetry of the phenomenal visual field. PMID- 8433909 TI - Effects of good form and spatial frequency on global precedence. AB - Does the global precedence effect depend on the goodness of the global form and low spatial frequencies? In Experiments 1 and 2, under a variety of attentional and task conditions, a global advantage in response time (RT) occurred in "good," many-element compound patterns but not in "poor," few-element patterns (unless the local elements were too small to be easily recognized). Symmetric interference effects were found in all patterns, however, suggesting that global and local information were encoded in parallel and that the global advantage in RT involved some postperceptual processes. Experiments 3A and 3B showed that the global advantage in RT and perceived pattern goodness depend on low spatial frequencies: Lowpass-filtered patterns rated as "good" showed the usual global advantage in RT, but highpass-filtered, many-element forms rated as "poor" did not. These findings suggest that a global advantage in RT requires an unambiguous global form conveyed by low spatial frequencies. PMID- 8433910 TI - The perceptual segregation of simultaneous vowels with harmonic, shifted, or random components. AB - This experiment was an investigation of the ability of listeners to identify the constituents of double vowels (pairs of synthetic vowels, presented concurrently and binaurally). Three variables were manipulated: (1) the size of the difference in F0 between the constituents (0, 1/2, and 6 semitones); (2) the frequency relations among the sinusoids making up the constituents: harmonic, shifted (spaced equally in frequency but not integer multiples of the F0), and random; and (3) the relationship between the F0 contours imposed on the constituents: steady state, gliding in parallel, or gliding in opposite directions. It was assumed that, in the case of the gliding contours, the harmonics of each vowel would "trace out" their spectral envelope and potentially improve the definition of the formant locations. It was also assumed that the application of different F0 contours would introduce differences in the direction of harmonic movement (common fate), thus aiding the perceptual segregation of the two vowels. The major findings were the following: (1) For harmonic constituents, a difference in F0 leads to improved identification performance. Neither tracing nor common-fate differences add to the effect of pitch differences. (2) For shifted constituents, a difference between the spacing of the constituents also leads to improved performance. Formant tracing and common fate contribute some further improvement. (3) For random constituents, tracing does not contribute, but common fate does. PMID- 8433911 TI - Attentional distribution in the visual field during same-different judgments as assessed by response competition. AB - Judgments of same and different on a comparison task have been found to be subject to response competition if an irrelevant stimulus is presented in the display along with the target stimuli. For example, the reaction time for judging two letters the same is markedly increased if a different but irrelevant letter is also present in the display (C. W. Eriksen, O'Hara, & B. [A.] Eriksen, 1982). We have made use of this competition effect to map the visual attentional field in two dimensions. In two experiments, we varied the size of the attended area by varying the separation of the comparison stimuli. The boundaries of the attended area were mapped by varying the location of a response-competitive irrelevant noise letter. On this task, the attended area was found to be elliptical in shape, with the location of the target stimuli defining the major axis. The minor axis of the ellipse increased in direct proportion to increases in the major axis. Rather than interpret these field effects in terms of areas of enhanced processing, we propose that instead they represent the limits or failures in inhibition of competing stimulation. PMID- 8433913 TI - Color stereopsis: a model for depth reversals based on border contrast. AB - Color stereopsis refers to the effect of stimulus color on perceived depth of stimuli viewed binocularly. It is well established and well understood that the wavelength of a stimulus affects its perceived depth in color stereopsis by prismatic effects in human optics, with long-wavelength stimuli normally seen in front of short-wavelength stimuli. It is less well known, and not well understood, that the background of the stimulus affects depth order as well. We demonstrate experimentally, using a long-wavelength orange stimulus and a short wavelength blue stimulus, that a change from black to white in the background at the border (a change in border contrast) of the stimulus changes the perceived depth order from orange in front of blue to blue in front of orange (a color reversal). We present a descriptive model to explain reversals in color stereopsis when stimuli are displayed on a white background and suggest that it may account for instances of color reversals that are currently unexplained or questionably explained by other models. PMID- 8433912 TI - Effects of spatial filtering and lack of effects of visual imagery on pattern contingent color aftereffects. AB - Checkerboards contain fundamental two-dimensional Fourier components oriented 45 degrees from the edges of individual checks. Previous studies have shown that contingent color aftereffects following adaptation to chromatic checkerboard stimuli were associated with the fundamental components rather than the edges. In the present experiments, we measured contingent color aftereffects, using the method of constant stimuli, after subjects adapted to unfiltered checkerboards and checkerboards with the fundamental Fourier components removed. The adaptation stimuli were magenta (or green) squares and green (or magenta) diamonds; the test stimuli were vertical or oblique sine-wave gratings with different saturations. After adaptation to unfiltered checkerboards, aftereffects contingent on the fundamental components were obtained. In contrast, after adaptation to filtered stimuli, aftereffects of smaller magnitude were found to be aligned with the edges. The data support the previous findings of spatial-frequency-contingent color aftereffects with checkerboard adaptation stimuli and indicate that the aftereffects can be associated with edges if the fundamental components of adaptation stimuli are removed by spatial filtering. We reexamined the possibility of color aftereffects induced by imagery of checkerboards. Contrary to the previous reports, no significant aftereffects were obtained. PMID- 8433914 TI - Processing interactions between segmental and suprasegmental information in native speakers of English and Mandarin Chinese. AB - The processing interactions between segmental and suprasegmental information in native speakers of English and Mandarin Chinese were investigated in a speeded classification task. Since in Chinese, unlike in English, tones convey lexically meaningful information, native speakers of these languages may process combinations of segmental and suprasegmental information differently. Subjects heard consonant-vowel syllables varying on a consonantal (segmental) dimension and either a Mandarin Chinese or constant-pitch (non-Mandarin) suprasegmental dimension. The English listeners showed mutual integrality with the Mandarin Chinese stimuli, but not the constant-pitch stimuli. The native Chinese listeners processed these dimensions with mutual integrality for both the Mandarin Chinese and the constant-pitch stimuli. These results were interpreted in terms of the linguistic function and the structure of suprasegmental information in Chinese and English. The results suggest that the way listeners perceive speech depends on the interaction between the structure of the signal and the processing strategies of the listener. PMID- 8433915 TI - Perceptual versus postperceptual mediation of visual context effects: evidence from the letter-superiority effect. AB - Two experiments demonstrated letter-context effects that cannot easily be accounted for by postperceptual theories based on structural redundancy, figural goodness, or memory advantage. In Experiment 1, subjects identified the color of a letter fragment more accurately in letter than in nonletter contexts. In Experiment 2, subjects identified the feature presented in a precued color more accurately in letters than in nonletters. We argue that these effects result from top-down perceptual processing. PMID- 8433916 TI - An experimental evaluation of three theories of auditory stream segregation. AB - Three theories of auditory stream segregation were evaluated. In two-part trials, subjects heard an induction sequence, whose effects upon an immediately subsequent test sequence were measured. The rhythm and total duration of Induction Sequence tones were varied in two experiments. The similarity between induction and test sequences aided segregation, but rhythmic predictability and longer tone durations did not. Frequency alternation during the induction sequence was not necessary to induce segregation in the test sequence. Furthermore, peripheral processes inadequately account for the segregation effects found. The data suggest that, once a distinct percept emerges from an auditory scene, properties derived from the percept (particularly changes) are fed back to control the ongoing analysis of that auditory scene. A neural adaptation to stimuli with constant properties may form part of this analysis. PMID- 8433917 TI - Infant use of relative motion as information for form: evidence for spatiotemporal integration of complex motion displays. AB - Previous studies of infants' ability to integrate and to utilize relative motion as information for form in the absence of structural cues have primarily involved motions that are uniform in rate, direction, and path within the form to be constructed. In the present study, we examined infants' ability to integrate relative motion information from motions that are nonuniform along these dimensions, and from this integrative process to construct a coherently rotating two-dimensional form. Infants' ability to integrate nonuniform motion was measured with regard to their ability to discriminate the rotating form from a noncoherent control display containing the same absolute motions. The results showed that discrimination of the coherent and incoherent displays was not demonstrated until 7 months of age. Two additional experiments were conducted to rule out the possibility that this discrimination was based on the detection of local regions of coherence, rather than the perception of the global rotating form. In both experiments, the results did not support discrimination based exclusively on local cues alone. From the combined results of all three experiments, we conclude that infants demonstrate the capacity to integrate the information contained within nonuniform trajectories into a coherent structure by 7 months of age. PMID- 8433918 TI - Preattentive and cognitive effects on perceptual completion at the blind spot. AB - Our findings indicate that preattentive processes, such as the filling in of homogeneously colored areas, discrete dots, or bars across the blind spot, take into account both the color and the form that stimulate the retina around the optic disk. Perceptual completion of the "junction" of two opposite colors facing each other on opposite sides of the blind spot was resolved by simultaneous segregation of the two colors at the location of a filled-in perpendicular line that suggested a boundary separating the two colors. Orientation preference and relative salience of one color versus the other determined which color was perceptually completed in a forced-choice situation that involved perceptual completion at the intersection of a cross formed by bars of opposite colors. A 1 min exposure to these stimuli presented an ambiguous situation for perceptual completion of either color within the blind spot, and resulted in a perceptual "flip-flop" from one color to the other, much like the phenomenon that occurs in figure reversal. Instructions to speed up this reversal process led to a fivefold reduction in latency to first reversal. PMID- 8433919 TI - Lateral information transfer across saccadic eye movements. AB - Our perception of the visual world remains stable and continuous despite the disruptions caused by retinal image displacements during saccadic eye movements. The problem of visual stability is closely related to the question of whether information is transferred across such eye movements--and if so, what sort of information is transferred. We report experiments carried out to investigate how presaccadic signals at the location of the saccade goal influence the visibility of postsaccadic test signals presented at the fovea. The signals were Landolt rings of different orientations. If the orientations of pre- and postsaccadic Landolt rings were different, the thresholds of the test signals were elevated by about 20%-25% relative to those at the static control condition. When the orientations were identical, no such elevation occurred. This selective threshold elevation effect proved to be a phenomenon different from ordinary saccadic suppression, although it was closely related to the execution of the saccadic eye movement. The consequences for visual stability are discussed. PMID- 8433920 TI - The spatial distribution of attention following an exogenous cue. AB - Three target-discrimination experiments were conducted to explore the spatial distribution of covert visual attention following an exogenous cue. On each trial, a brief peripheral onset was followed by a target stimulus in an otherwise empty visual field at one of eight (Experiment 1) or one of four (Experiments 2 and 3) possible locations centered at the fixation point. The spatial relation between the cue and the target was manipulated. The main results were that (1) performance was better at the cued location than at another nearby location in the same visual quadrant; (2) performance was not affected by the major horizontal and vertical visual meridians; and (3) performance was affected by the spatial distance between the cued and target locations. Together, the results suggest that the spatial distribution of exogenously oriented attention can be most easily integrated with a simple gradient model. PMID- 8433921 TI - The logic of misperceived distance (or location) theories of the Poggendorff illusion. AB - For the Poggendorff display (transversal interrupted by parallel lines), the typical distance-misperception theory postulates that a particular linear distance extending across the empty space between parallels is underestimated; examples are the intertransversal slant distance defined by the closest ends of the transversal segments (a "wings-in Muller-Lyer like" underestimation) or the perpendicular distance between parallels (parallels "attract"). Distance misperception by itself, however, can neither establish that perceived transversal misalignment exists for a Poggendorff display nor specify the perceived-location condition(s) that will produce perceptual collinearity. The perceptual displacement vector is introduced as a means of specifying fully the perceptual mislocation (displacement) of one transversal segment with respect to the other. Given this vector information (direction as well as distance), the logical soundness of theories postulating distance or location misperception were evaluated, and they were compared on the basis of extant data. Such vector information can be used to evaluate other classes of theories as well. PMID- 8433922 TI - The evolution of black nursing associations. PMID- 8433923 TI - New Jersey State Nurses' Association history. What is past is prologue. PMID- 8433924 TI - Needle exchange project recommended for New Jersey. PMID- 8433925 TI - Initiatives in gerontological nursing education: the role of the American Nurses Association's council on gerontological nursing. PMID- 8433926 TI - National League for Nursing: initiatives in gerontological nursing education. PMID- 8433927 TI - National consensus conference on gerontologic nursing competencies. PMID- 8433928 TI - Enhancing gerontological nursing knowledge through curriculum and collaboration. PMID- 8433929 TI - Southern Regional Education Board teaching gerontological nursing project. PMID- 8433930 TI - The community college-nursing home partnership. PMID- 8433931 TI - Model gerontological clinical sites project. PMID- 8433932 TI - Partners in care in a retirement community. PMID- 8433933 TI - Setting the agenda for gerontological nursing education. PMID- 8433934 TI - Gerontological nursing issues and opportunities for twenty-first century "not for the weak of heart: the politics of long-term care". PMID- 8433935 TI - Issues and opportunities for the twenty-first century: the search for a definition of quality in long-term care settings. PMID- 8433936 TI - New practice models in long-term care. PMID- 8433937 TI - The nursing home clinical: new horizons for capitalizing on a caring experience. PMID- 8433938 TI - Relationships in clinical teaching: the faculty role revisited. PMID- 8433939 TI - Gerontologic nursing competency development: Associate Degree in Nursing & Bachelor of Science in Nursing: history--commonalities--differences. PMID- 8433941 TI - About anger and power. PMID- 8433940 TI - Facilitating student learning: effective teaching strategies for baccalaureate education. PMID- 8433942 TI - A symphony of caring: shared visions and eloquent futures for nursing education and practice. PMID- 8433943 TI - [Why should we defend the Scandinavian languages?]. PMID- 8433944 TI - [The Anders Annual Prize for young researchers 1992. Identification of genes in human diseases]. AB - The localisation and identification of the genes for human diseases are most important aspects of human gene mapping. The identification of a disease gene immediately defines the function of the respective chromosomal region. In other words, the identification and characterisation of morbid mutations provide a short-cut to the definition of specific functions of certain parts of the human genome. Professor Leena Peltonen Palotie has been awarded the Anders Jahre prize for young scientists for her basic research into hereditary diseases, particularly the Marfan syndrome and aspartyl-glucosaminuria. PMID- 8433945 TI - [Treatment of psoriasis]. AB - About two per cent of the Scandinavian population have manifest psoriasis, which may vary in distribution and duration. With a chronic progressive disease such as psoriasis, it is especially important to weigh the effect of treatment against its tolerance by the patient and the risk of side effects. Recent advances in pharmacology have markedly increased the range of treatment available in severe cases of psoriasis, and the recent introduction of local treatment with vitamin D has resulted in a broader range of treatment for patients with mild or moderate psoriasis. However, no curative treatment is yet within sight. PMID- 8433947 TI - [Educational team work in Scandinavian Sports medicine]. PMID- 8433946 TI - [Service for rape victims in Oslo]. AB - The article presents the medical rape trauma service in Oslo, Norway. The rape trauma service was established in 1986 at the Emergency Hospital and serves all population in Oslo. The patient is offered a medical examination, a medico-legal documentation and evidence collection, crisis counselling, a stay at the observational ward, a victims lawyer, help to report to the police, a medical follow-up and a psycho-social follow-up. All treatment is free and the patient's choice. There is no obligation to report to the police. The number of rape victims being medically examined has increased four times compared to the average number of rape victims before the trauma service opened. PMID- 8433948 TI - [Calcitonin as medication in pain?]. AB - An antinociceptive effect of calcitonin has been reported in numerous studies on both animals and humans. In the present article, we review the controlled clinical studies in which calcitonin has been used to relieve skeletal pain (cancer metastases, osteoporotic fractures) as well as extraskeletal pain (phantom limb pain, neurogenic claudication, reflex sympathetic dystrophy, migraine). To date, a positive effect of calcitonin is well documented against placebo in short-term treatment of skeletal pain. However, for long-term treatment of skeletal pain, and for the treatment of extraskeletal pain, the present documentation is insufficient. No controlled trials against conventional analgesic treatment is published. Thus, further studies are required before the place of calcitonin in pain therapy can be established. PMID- 8433949 TI - [Reliability of Norwegian suicide statistics]. AB - New laws have radically changed the registration procedure of suicides in Norway, and a new Death Certificate Form makes it more difficult for doctors to cover up a suicide. The changes in the registration procedure may be responsible for a substantial part of the alarming rise in the Norwegian suicide rate from the 60's to the 80's. The Norwegian and the Danish suicide rates from the early 60's are not at all comparable. Neither are the Norwegian rates of the 60's comparable to those of the 80's. A comparison between suicide rates in different countries is near to worthless without an intimate knowledge of the basis for the diagnosis of suicide in the countries concerned. PMID- 8433950 TI - [How can we understand each other better in Scandinavia!]. PMID- 8433951 TI - AIDS and the gastrointestinal tract. AB - Gastrointestinal disease in AIDS most often affects three major areas: the bowel, the esophagus, and the liver. Investigation should be tailored to identify treatable causes of disease, bearing in mind that multiple infections, superinfection, and untreatable diseases are common. Clinical decisions must be made regarding both the level of investigation necessary and the best testing procedures to use. Treatment is often only symptomatic, but in some cases a specific pathogen can be targeted. PMID- 8433952 TI - When your obese patient can't lose weight. AB - "I can't lose weight" is a frequent refrain among obese patients. Even though a patient desires to lose extra pounds and apparently is complying with his or her physician's recommendations, the expected weight loss often does not occur. To achieve a more successful outcome in obese patients, the authors suggest that physicians become active rather than passive participants in the weight loss regimen. PMID- 8433953 TI - Food allergy. Manifestations, evaluation, and management. AB - Allergic reactions to food are more common among infants and children but occur in adults as well. Foods that are most often implicated in allergic reactions are eggs, cow's milk, nuts, wheat, soy products, whitefish, and crustacea. Gastrointestinal, respiratory tract, and dermatologic symptoms, as well as systemic anaphylaxis, may develop. In addition to history taking and physical examination, the workup may include skin testing, the radioallergosorbent test, and double-blind oral food challenge. Avoidance of offending antigens is the most important aspect of treatment. If exposure occurs, antihistamines and epinephrine may be needed for treatment of an acute reaction. PMID- 8433954 TI - Alcoholism in the elderly. Uncovering a hidden problem. AB - Currently, about 12% of people in the United States are elderly, and this age group is one of the most rapidly expanding segments of the population. The incidence of alcoholism in older persons is increasing, and diagnosis can be difficult. Because of age-related physiologic changes, the effects of alcohol are more pronounced in older persons. Furthermore, alcoholism may mimic the effects of aging and many conditions prevalent in this age-group. A high index of suspicion, together with thorough history taking and recognition of the clinical features of alcoholism in the elderly, can aid early detection and appropriate management. PMID- 8433955 TI - A preview of more government. The latest in the OSHA saga. PMID- 8433956 TI - Changes in healthcare financing. PMID- 8433957 TI - OSHA breaks a rule. PMID- 8433958 TI - OSHA breaks a rule. PMID- 8433959 TI - Abnormal uterine bleeding. Finding and treating the cause. AB - Abnormal vaginal bleeding is a common presenting symptom with an extensive list of potential causes. In evaluating abnormal bleeding, nonuterine causes and pregnancy should first be excluded; after that, it is important to differentiate between ovulatory and anovulatory bleeding (dysfunctional uterine bleeding). Initial laboratory tests, in addition to a sensitive pregnancy test, include hemoglobin and hematocrit determinations, platelet count, and occasionally coagulation studies. An endometrial biopsy or dilation and curettage may be necessary to rule out endometrial hyperplasia or other pathology associated with the long-term unopposed estrogen stimulation experienced by anovulatory patients. In evaluating abnormal ovulatory bleeding, hysteroscopy with selected biopsy or curettage is superior to routine dilation and curettage. Anovulatory patients should be treated with an oral progestin, an oral contraceptive, or, if pregnancy is desired, an ovulation stimulant. Treatment options for patients having ovulatory cycles include an oral contraceptive, an oral progestin, danazol (Danocrine), a gonadotropin-releasing hormone agonist, mefenamic acid (Ponstel), and surgery. PMID- 8433960 TI - Pelvic inflammatory disease. Current diagnostic criteria and treatment guidelines. AB - Pelvic inflammatory disease (PID) is a common infection in women of reproductive age. PID is actually a spectrum of disease, beginning with cervicitis and progressing to endometritis and eventually salpingitis. Sequelae include ectopic pregnancy, infertility, chronic pelvic pain, hydrosalpinx, and tubo-ovarian abscess. Neisseria gonorrhoeae and Chlamydia trachomatis are the primary causes of PID. Chlamydial infection may be asymptomatic, and the resulting salpingitis is often referred to as "silent PID." Polymicrobial infection with other organisms (eg, anaerobes, facultative aerobes) may be initiated by gonorrhea, chlamydial infection, or both. Early recognition of infection, prompt institution of appropriate antibiotic therapy, and proper follow-up are important to prevent the sequelae of PID. Patient education is essential to reduce the incidence of PID. PMID- 8433961 TI - Treating hypertensive emergencies. Controlled reduction of blood pressure and protection of target organs. AB - Diastolic blood pressure of 120 mm Hg or more is often cited as identifying a hypertensive crisis. However, the absolute level of blood pressure may not be as important as the rate of increase. One important feature that distinguishes hypertensive emergency from hypertensive "urgency" is the ongoing vascular damage that occurs with hypertensive emergency. When this is present, therapy should be initiated as soon as possible. The initial goal is to reduce mean arterial pressure about 15% to 25% within the first 48 hours. Overzealous or uncontrolled reduction in blood pressure may result in coma, stroke, myocardial infarction, acute renal failure, or death. Thus, a drug with titratable dosing (eg, intravenous nitroprusside sodium [Nipride, Nitropress]) is preferred in most situations. Patients with hypertensive urgency do not have evidence of vascular damage. Usually, they are asymptomatic, have no retinal lesions, and have a marked elevation in diastolic blood pressure. Hypertensive urgency does not require immediate normalization of blood pressure, but initiation of therapy and careful follow-up are critical. PMID- 8433962 TI - Unraveling the mechanism of protein folding: new tricks for an old problem. PMID- 8433963 TI - Restructuring an interdomain linker in the dihydrolipoamide acetyltransferase component of the pyruvate dehydrogenase complex of Escherichia coli. AB - The lipoyl, subunit-binding and catalytic domains of the dihydrolipoamide acetyltransferase subunits (E2p) of the Escherichia coli pyruvate dehydrogenase complex are connected by linker sequences which are characteristically rich in alanine and proline residues. By facilitating domain movement these linkers are thought to promote interactions between the three types of active site that participate in the catalytic cycle of the complex. To investigate functional constraints associated with linker composition and sequence, the natural linker of an E2p subunit containing one lipoyl domain was replaced by shorter sequences containing: mixtures of alanine plus proline residues; mainly alanine; mainly proline; and mainly charged residues. Each artificial linker possessed a central histidine residue for assessing linker flexibility by 1H-NMR spectroscopy. The resultant complexes exhibited 181% (proline), 74-79% (alanine plus proline), 63% (alanine) and 7% (charged residues) of parental activity compared with a value of 75% expected for a complex with a comparably shortened linker. The 1H-NMR spectra showed that the alanine plus proline linkers are flexible but the alanine linker and the proline linker are relatively inflexible. Substantial variations in linker sequence and composition were tolerated without loss of function, and the enhanced activity conferred by the proline linker was attributed to the combined effects of length and relative inflexibility. PMID- 8433964 TI - The random peptide library-assisted engineering of a C-terminal affinity peptide, useful for the detection and purification of a functional Ig Fv fragment. AB - The facile detection and purification of a recombinant protein without detailed knowledge about its individual biochemical properties constitutes a problem of general interest in protein engineering. The use of a novel kind of random peptide library for the stepwise engineering of a C-terminal fusion peptide which confers binding activity towards streptavidin is described in this study. Because of its widespread use as part of a variety of conjugates and other affinity reagents, streptavidin constitutes the binding partner of choice both for detection and purification purposes. The streptavidin-affinity tag was engineered at the C-terminus of the VH domain as part of the D1.3 Fv fragment which was functionally expressed in Escherichia coli. Irrespective of whether it was displayed by the VH or the VL domain, the optimized version of the affinity peptide termed 'Strep-tag' allowed the detection of the Fv fragment both on Western blots and in ELISAs by a streptavidin-alkaline phosphatase conjugate. In addition, the one-step purification of the intact Fv fragment carrying a single Strep-tag at the C-terminus of only one of its domains was achieved by affinity chromatography with streptavidin-agarose using very mild elution conditions. PMID- 8433965 TI - A catalytically-impaired class A beta-lactamase: 2 A crystal structure and kinetics of the Bacillus licheniformis E166A mutant. AB - In the beta-lactamase (penicillinase) of Bacillus licheniformis 749/C, site specific mutation of Glu166 to Ala caused a million-fold reduction of catalytic activity towards both penicillin and cephalosporin substrates and resulted in the stoichiometric accumulation of the acyl enzyme. The rate of deacylation generally slowed by as much as 10(-7) compared to the wild type. The acyl enzyme intermediate was observed by HPLC, but not by X-ray diffraction. The mutant was crystallized from methoxyPEG 5000 at pH 6.2 in space group P2(1) with Z = 4. Molecular replacement based on the wild type structure followed by refinement produced an R factor of 17.2% for 25,800 3 sigma data from 10 to 2 A. Deviations from bond and angle ideals are 0.005 A and 1.5 degrees respectively. The mutant differs very little from the wild type structure, with only 0.25 A (r.m.s.) differences in backbone atoms; the CD spectra and thermal stabilities of the two enzymes are identical. Changes in the positions of the reactive Ser70 and conserved Lys73 are not significant, suggesting that the proposed salt linkage to Glu166 in the wild type enzyme is weak or non-existent. The calculated solvent exposure of Ser70 and Lys73 increases slightly and a buried water molecule is now positioned near Lys73. The hydrolytic water seen in the native active site shifts markedly by 1.6 A, but is held in the active site by Asn170, which possibly becomes an ineffective substitute for Glu166 in activating the water for deacylation. PMID- 8433966 TI - Overproduction and purification of the regulatory subunit of Escherichia coli aspartate transcarbamoylase. AB - An Escherichia coli strain/plasmid system has been developed for the overexpression of the regulatory subunit of E. coli aspartate transcarbamoylase (ATCase). Production of large quantities of regulatory subunit, by the method described here, should facilitate future experiments, such as X-ray crystallography, NMR and hybridization experiments, aimed at understanding the heterotropic mechanism that regulates the activity of ATCase. The plasmid used for the over-expression carries the gene for the regulatory subunit, pyrI, downstream from the strong pyrB promoter. The host strain, EK1104 [Nowlan, S.F. and Kantrowitz, E.R. (1985) J. Biol. Chem., 260, 14712-14716] carries a deletion in the pyrBI region of the chromosome, as well as a leaky pyrF allele. When this strain/plasmid system is grown under limiting pyrimidine levels, large quantities of the regulatory subunit of ATCase are produced without any trace of catalytic subunit or holoenzyme. A procedure for the purification of the regulatory subunit from cell extracts has also been developed yielding approximately 50 mg of purified regulatory subunit per liter of initial culture. The regulatory subunit produced in this fashion is fully competent in reassociation experiments with the native catalytic subunit. Furthermore, the reassociated holoenzyme exhibits kinetic properties identical to those of the wild type enzyme. In addition, we report the construction of a pUC119 based plasmid which carries a unique NdeI site at the fMet of the pyrB gene of ATCase. This plasmid, which was used in the construction of the system for the overexpression of the regulatory subunit of ATCase, has been shown to be of general use for the expression of foreign proteins in E. coli. PMID- 8433967 TI - Molecular dynamics simulation of winter flounder antifreeze protein variants in solution: correlation between side chain spacing and ice lattice. AB - The solution structure of the 38 amino acid C-terminal region of the precursor for the HPLC-6 antifreeze protein from winter flounder has been investigated with molecular dynamics using the AMBER software. The simulation for the peptide in aqueous solution was carried out at a constant temperature of 0 degree C and at atmospheric pressure. The simulation covered 120 ps and the results were analyzed based on data sampled upon reaching a stable equilibrium phase. Information has been obtained on the quality of constant temperature and pressure simulations, the solution structure and dynamics, the hydrogen bonding network, the helix stabilizing role of terminal charges and the interaction with the surrounding water molecules. The Lys18-Glu22 interactions and the terminal charged residues are found to stabilize a helical structure with the side chains of Thr2, Thr13, Thr24 and Thr35 equally spaced on one side of the helix. The spacing between oxygen atoms in the hydroxyl group of the threonine side chains exhibits fluctuations of the order of 2-3 A during the 120 ps of simulation, but values simultaneously close to the repeat distance of 16.6 A between oxygen atoms along the [0112] direction in ice are observed. Furthermore, two engineered variants were studied using the same simulation protocol. PMID- 8433968 TI - The prediction and characterization of metal binding sites in proteins. AB - The rational engineering of novel functions into proteins can only be attempted when the underlying structural scaffold on which the new function is displayed and the structure of the target protein are both well understood. To introduce functions mediated by metals it is therefore necessary to identify the principal liganding residues for the chosen metal, the required architecture of the metal ligand complex and sites within the target protein that could accommodate such sites. Here we present a method that applies structural information from the protein data bank to the ab initio design and characterization of novel metal binding sites. The prediction method has been tested on 28 metalloprotein structures from the Brookhaven Protein Data Bank. It successfully identified > 90% of the metal binding sites. In addition, we have used the method to design and characterize zinc binding sites in two antibody structures. Metal binding studies on one of these putative metalloantibodies showed metal binding, confirming the predictive power of the method. PMID- 8433969 TI - ALSCRIPT: a tool to format multiple sequence alignments. PMID- 8433970 TI - Proposed structure for the DNA-binding domain of the helix-loop-helix family of eukaryotic gene regulatory proteins. AB - A modelled tertiary structure for the dimeric HLH domain of the E47 protein is presented. Structural information was obtained from the aligned sequences of > 40 members of the HLH family. The information was used to model each monomer as an alpha-helical hairpin, with knobs-into-holes packing of side-chains as found in antiparallel coiled-coil. The dimer forms a four-helix bundle with additional knobs-into-holes packing at the dimer interface. The size and electrostatic properties of core-forming residues are all accounted for in the model. The model does not violate any known properties of protein structure. The monomers are related by two-fold rotational symmetry, in agreement with the observed DNA binding sites which are imperfect inverted repeats. The N-terminal basic region, in which DNA binding and base specificity reside, forms the first part of helix 1. A prediction based on the model structure is that the HLH domains do not bind to DNA in its B form but require a partially unwound conformation in order to enter the major groove. PMID- 8433971 TI - Molecular modeling of coiled-coil alpha-tropomyosin: analysis of staggered and in register helix-helix interactions. AB - In register and staggered models of tropomyosin coiled-coil were built from X-ray C alpha coordinates and refined via molecular dynamics. The two models show similar structural features with the X-ray structure of GCN4 leucine zipper. Empirical energetic methods used to compare the in register and staggered models indicate that both are equally probable. The two models have similar profiles of solvation free energy of folding for residues at positions a and d of the repeating heptad, indicating that residues at these positions are as well buried in an in register structure as in a staggered one. Neither the in register nor the 14 residues staggered structure can be ruled out based on hydrophobic or e-g' (g-e') electrostatic interactions which are not able to distinguish between the two models and are therefore not selective. However, the eg-b'c' electrostatic interactions, although smaller in magnitude, are in favor of the in register model. Furthermore, analysis of hydrophobic and electrostatic interactions along the tropomyosin sequence shows that bulky residues in positions a and d prevent the formation of inter-chain salt bridges. PMID- 8433972 TI - Functional roles and subsite locations of Leu177, Trp178 and Asn182 of Aspergillus awamori glucoamylase determined by site-directed mutagenesis. AB - Fungal glucoamylases contain four conserved regions. One region from the Aspergillus niger enzyme contains three key carboxylic acid residues, the general acid catalytic group, Glu179, along with Asp176 and Glu180. Three site-directed mutations, Leu177-->His, Trp178-->Arg and Asn182-->Ala, were constructed near these acidic groups to reveal the function of other conserved residues in this region. Leu177 and Trp178 are strictly conserved among fungal glucoamylases, while an amide, predominantly Asn, always occurs at position 182. Substitutions of Leu177 or Trp178 cause significant decreases in kcat with the substrates tested. Similar increases in activation energies obtained with Leu177-->His with both alpha-(1,4)- and alpha-(1,6)-linked substrates indicate Leu177 is located in subsite 1. KM values obtained with the Trp178-->Arg mutation increase for an alpha-(1,6)-linked substrate, but not for alpha-(1,4)-linked substrates. Calculated differences in activation energy between substrates indicate Trp178 interacts specifically with subsite 2. The Asn182-->Ala mutation did not change kcat or KM values, indicating that Asn182 is not crucial for activity. These results support a mechanism for glucoamylase catalytic activity consisting of a fast substrate binding step followed by a conformational change at subsite 1 to stabilize the transition state complex. PMID- 8433973 TI - Comparative stability of dihydrofolate reductase mutants in vitro and in vivo. AB - Dihydrofolate reductase mutants with amino acid replacements in the active center (Thr35-->Asp mutant, Arg57-->His mutant and the mutant with triple replacement Thr35-->Asp, Asn37-->Ser, Arg57-->His) were obtained by site-directed mutagenesis. The stabilization effect of trimethoprim and NADP.H on the protein tertiary structure in vitro has been investigated. In the case of mutants with a 'weak' tertiary structure (Thr35-->Asp35 and the triple mutant) the separate addition of ligands does not affect their stability. The simultaneous addition of these ligands to Thr35-->Asp35 and the triple mutant leads to the large increase in their stability. A distinct correlation was found between the in vitro studied stability of the mutant proteins to the urea- or heat-induced denaturation and the level of proteolytic degradation of these mutants previously observed in vivo. PMID- 8433974 TI - Site-directed mutagenesis study on the roles of evolutionally conserved aspartic acid residues in human glutathione S-transferase P1-1. AB - The evolutionally conserved aspartyl residues (Asp57, Asp98 and Asp152) in human glutathione S-transferase P1-1 were replaced with alanine by site-directed mutagenesis to obtain the mutants (D57A, D98A and D152A). The replacement of Asp98 with alanine resulted in a decrease of the affinity for S-hexyl-GSH agarose, a 5.5-fold increase of the KmGSH and a 2.9-fold increase of the I50 of S hexyl-GSH for GSH-CDNB conjugation. Asp98 seems to participate in the binding of GSH through hydrogen bonding with the alpha-carboxylate of the gamma-glutamyl residue of GSH. The kcat of D98A was 2.6-fold smaller than that of the wild-type, and the pKa of the thiol group of GSH bound in D98A was approximately 0.8 pK units higher than those in the wild-type. Asp98 also seems to contribute to the activation of GSH to some extent. On the other hand, most of the kinetic parameters of D57A and D152A were similar to those of the wild-type. However, the thermostabilities of D57A and D152A were significantly lower than that of the wild-type. Asp57 and Asp152 seem to be important for maintaining the proper conformation of the enzyme. PMID- 8433975 TI - Supramolecular effects and molecular discrimination by macrocyclic hosts embedded in synthetic bilayer membranes. AB - Hybrid assemblies were prepared in combinations of a synthetic lipid, involving an L-alanine residue interposed between an anionic head group and a hydrophobic double-chain segment, with cage-type cyclophanes having a three-dimensionally extended hydrophobic cavity. Incorporation behavior of the cage-type hosts into the multi- and single-walled vesicules was characterized by highly sensitive differential scanning calorimetry and dynamic light-scattering measurements as well as by gel-filtration chromatography and electronic absorption spectroscopy. Both hosts were found to be completely incorporated into a relatively polar domain close to the vesicular surface. Anionic guest molecules, such as naphthol yellow S, dimethylsulfonazo III, bromopyrogallol red, and orange G, were effectively incorporated into the hydrophobic cavities provided by the cage-type cyclophanes embedded in the single-walled bilayer membrane, as confirmed by circular dichroism spectroscopy; the formation constants for 1:1 host-guest complexes were in the order of 10(4)-10(5) mol.dm-3. This means that the binding affinities of the cage-type hosts are largely retained even when the hosts are incorporated into the vesicle. Moreover, the pyridinium moieties bound to the chiral L-valine residues in the bridging components of the hosts underwent conformational changes upon inclusion of the guest, as confirmed by circular dichroism spectroscopy and molecular mechanics and dynamics calculations. PMID- 8433976 TI - Molecular recognition analyzed by docking simulations: the aspartate receptor and isocitrate dehydrogenase from Escherichia coli. AB - Protein docking protocols are used for the prediction of both small molecule binding to DNA and protein macromolecules and of complexes between macromolecules. These protocols are becoming increasingly automated and powerful tools for computer-aided drug design. We review the basic methodologies and strategies used for analyzing molecular recognition by computer docking algorithms and discuss recent experiments in which (i) substrate and substrate analogues are docked to the active site of isocitrate dehydrogenase and (ii) maltose binding protein is docked to the extracellular domain of the receptor, which signals maltose chemotaxis. PMID- 8433977 TI - Design of a metallo-bZIP protein that discriminates between CRE and AP1 target sites: selection against AP1. AB - The bZIP class of dimeric DNA binding proteins is characterized by a motif containing two discrete domains: a DNA contact domain defined by conserved basic and hydrophobic residues (basic domain), and a dimerization domain identified by a heptad repeat of leucine residues (zipper domain). Molecules are constructed in which the GCN4 dimerization domain is replaced by a series of stereochemically defined metal ion complexes that alter systematically the relative orientation of the basic domain peptides. Both the affinity and the specificity of DNA binding are modulated by seemingly small changes in metal complex stereochemistry. Although GCN4 binds CRE (ATGACGTCAT) and AP1 (ATGACTCAT) target sites with comparable affinity, one metallo-bZIP peptide ([G29Ts]2Fe) prefers the CRE by 4 kcal.mol-1 (1 cal = 4.184 J). Competition experiments performed with several DNAs demonstrate that discrimination between CRE and AP1 is dominated by selection against the AP1 site. PMID- 8433978 TI - Two light-transducing membrane proteins: bacteriorhodopsin and the mammalian rhodopsin. AB - Site-directed mutagenesis has provided insight into the mechanisms of action of bacteriorhodopsin and rhodopsin. These studies are summarized here. PMID- 8433979 TI - Toward an estimation of binding constants in aqueous solution: studies of associations of vancomycin group antibiotics. AB - An approach toward the estimation of binding constants for organic molecules in aqueous solution is presented, based upon a partitioning of the free energy of binding. Consideration is given to polar and hydrophobic contributions and to the entropic cost of rotor restrictions and bimolecular associations. Several parameters (derived from an analysis of entropy changes upon the melting of crystals and from the binding of cell wall peptide analogues to the antibiotic ristocetin A) which may be useful guides to a crude understanding of binding phenomena are presented: (i) amide-amide hydrogen bond strengths of -(1 to 7) +/- 2 kJ.mol-1, (ii) a hydrophobic effect of -0.2 +/- 0.05 kJ.mol-1.A-2 of hydrocarbon removed from exposure to water in the binding process, and (iii) free energy costs for rotor restrictions of 3.5-5.0 kJ.mol-1. The validity of the parameters for hydrogen bond strengths is dependent on the validity of the other two parameters. The phenomenon of entropy/enthalpy compensation is considered, with the conclusion that enthalpic barriers to dissociations will result in larger losses in translational and rotational entropy in the association step. The dimerization of some vancomycin group antibiotics is strongly exothermic (-36 to -51 kJ.mol-1) and is promoted by a factor of 50-100 by a disaccharide attached to ring 4 (in vancomycin and eremomycin) and by a factor of ca. 1000 by an amino sugar attached to the benzylic position of ring 6 in eremomycin. The dimerization process (which, as required for an exothermic association, appears to be costly in entropy) may be relevant to the mode of action of the antibiotics. PMID- 8433980 TI - Energetics of cooperative binding of oligonucleotides with discrete dimerization domains to DNA by triple helix formation. AB - Cooperativity in oligonucleotide-directed sequence-specific recognition of DNA by triple helix formation can be enhanced by the addition of discrete dimerization domains. The equilibrium association constants for cooperative binding of oligonucleotides that dimerize by Watson-Crick hydrogen bonds and occupy adjacent sites on double helical DNA by triple helix formation have been measured by quantitative affinity cleavage titration. For two oligonucleotides that bind unique neighboring 11-bp and 15-bp sites on double helical DNA, and dimerize by formation of an 8-bp Watson-Crick mini-helix, the free energy of binding is -8.0 and -9.7 kcal.mol-1, respectively, and the cooperative energy of interaction is 2.3 kcal.mol-1 (1 kcal = 4.18 kJ). The energetics of this artificial nucleic acid cooperative intermolecular assembly can mimic naturally occurring cooperative protein-DNA systems, such as the phage lambda repressor. PMID- 8433981 TI - Chemically bonded stationary phases that use synthetic hosts containing aromatic binding clefts: HPLC analysis of nitro-substituted polycyclic aromatic hydrocarbons. AB - The synthesis of hosts with improved binding affinities for nitroaromatic guests is described. Association constants for several host-guest complexes were measured in chloroform solution and ranged over three orders of magnitude. Two hosts were covalently linked to silica gel to produce chemically bonded stationary phases for HPLC. The use of these phases for HPLC analysis of nitro substituted polycyclic aromatic hydrocarbons is discussed. PMID- 8433982 TI - Histidine residue in the zinc-binding motif of aminopeptidase A is critical for enzymatic activity. AB - The murine BP-1 antigen (also called 6C3) is a homodimeric, phosphorylated cell surface glycoprotein that is expressed on immature B-lineage cells, bone marrow stromal cell lines, thymic cortical epithelial cells, endothelial cells, enterocytes, and renal proximal tubular cells. The amino acid sequence deduced from a BP-1 cDNA predicted a type II integral membrane protein with a zinc binding motif (His-Glu-Xaa-Xaa-His) found in zinc-dependent metallopeptidases, and functional analysis suggested that BP-1 is aminopeptidase A [APA; L-alpha aspartyl(L-alpha-glutamyl)-peptide hydrolase, EC 3.4.11.7]. Here we constructed an expression vector in which the BP-1 cDNA was placed downstream from the SR alpha promoter and used this construct to transfect COS-7 and Ltk- cells. Both transfectants expressed the BP-1 antigen on the cell surface and APA activity. The enzymatic activity of recombinant APA was increased by Ca2+ and inhibited by Zn2+, consistent with previous reports with purified APA. Point mutation of one of the histidine residues in the zinc-binding motif to phenylalanine completely abolished APA enzymatic activity, suggesting the structure of the zinc-binding motif of APA is critical for catalytic activity. Both wild-type and mutant BP-1 were glycosylated, transported to the cell surface, and possessed molecular weights similar to native BP-1 molecules on the murine 18.81 pre-B-cell line. The successful expression of both wild-type and mutant APA should allow more precise analysis of the diverse physiological roles of this ectoenzyme. PMID- 8433983 TI - Identification of two distinct properties of class II major histocompatibility complex-associated peptides. AB - We have examined the interactions of various peptides with the mouse class II major histocompatibility complex molecule I-Ak. The peptides were derived from the model protein hen egg white lysozyme (HEL). The immunodominant peptide of HEL is a 10-mer, residues 52-61. Our previous work established that this sequence contains the key residues for binding and presentation to T cells. Now we show that the binding of this 10-mer sequence resulted in complexes of I-Ak and peptide that, in SDS/PAGE (without boiling the protein), rapidly dissociated from the component alpha and beta chains. The binding interactions were studied in vitro, by incubating purified I-Ak and radiolabeled peptide, or ex vivo, by using antigen-presenting cells incubated with peptides. Peptides with additional residues at either the amino or carboxyl terminus behaved dramatically differently. Complexes of I-Ak with the longer peptides were stable to SDS/PAGE. Very few amino acid additions result in the change from unstable to stable complexes. The important issue here is that when cultured with HEL, antigen presenting cells selected the HEL peptides containing the 52-61 sequences that favored stability [Nelson, C. A., Roof, R. W., McCourt, D. W. & Unanue, E. R. (1992) Proc. Natl., Acad. Sci. USA 89, 7380-7383]. Also, from other studies, such sequences correlate with a high immunogenicity of the peptide. We conclude that there are structural features of peptides that change the stability of the class II molecule and that are independent of the "core" peptide seen by the T cells. PMID- 8433984 TI - Stimulation of Mn peroxidase activity: a possible role for oxalate in lignin biodegradation. AB - Oxalate is produced by numerous wood-degrading fungi. Our studies here show that the white-rot fungus Phanerochaete chrysosporium produces extracellular oxalate under conditions that induce synthesis of the ligninolytic system. Little or no oxalate was detected in cultures grown under high nutrient nitrogen or carbon. This extracellular oxalate was identified and quantitated by HPLC. Its identity was further substantiated by its decomposition by the enzyme oxalate oxidase. The oxalate content of the extracellular fluid (peaking at 60 microM) paralleled the extracellular activity of the lignin-degrading enzyme, Mn peroxidase. Significantly, we demonstrated that oxalate, at physiological concentrations, substantially stimulated Mn peroxidase-catalyzed phenol red oxidation, presumably by its ability to chelate Mn. Stopped flow studies also indicate that oxalate accelerates the turnover of Mn peroxidase. Furthermore, we discovered that oxalate can support Mn peroxidase-catalyzed oxidations in the absence of exogenous H2O2 and in the presence of dioxygen. These results allow us to propose an important role for oxalate, a ubiquitous compound produced by wood-destroying fungi, in lignin biodegradation. PMID- 8433985 TI - Daidzin: a potent, selective inhibitor of human mitochondrial aldehyde dehydrogenase. AB - Human mitochondrial aldehyde dehydrogenase (ALDH-I) is potently, reversibly, and selectively inhibited by an isoflavone isolated from Radix puerariae and identified as daidzin, the 7-glucoside of 4',7-dihydroxyisoflavone. Kinetic analysis with formaldehyde as substrate reveals that daidzin inhibits ALDH-I competitively with respect to formaldehyde with a Ki of 40 nM, and uncompetitively with respect to the coenzyme NAD+. The human cytosolic aldehyde dehydrogenase isozyme (ALDH-II) is nearly 3 orders of magnitude less sensitive to daidzin inhibition. Daidzin does not inhibit human class I, II, or III alcohol dehydrogenases, nor does it have any significant effect on biological systems that are known to be affected by other isoflavones. Among more than 40 structurally related compounds surveyed, 12 inhibit ALDH-I, but only prunetin and 5-hydroxydaidzin (genistin) combine high selectivity and potency, although they are 7- to 15-fold less potent than daidzin. Structure-function relationships have established a basis for the design and synthesis of additional ALDH inhibitors that could both be yet more potent and specific. PMID- 8433986 TI - Characterization of PDH beta 1, the structural gene for the pyruvate dehydrogenase beta subunit from Saccharomyces cerevisiae. AB - The gene encoding the pyruvate dehydrogenase (PDH) beta subunit (E1 beta) of the PDH complex from Saccharomyces cerevisiae has been cloned, sequenced, disrupted, and expressed. Two overlapping DNA fragments were generated from a yeast genomic DNA library by the polymerase chain reaction with synthetic oligonucleotide primers based on amino acid sequences of the yeast and human E1 beta subunits. The DNA fragments were subcloned and sequenced. The composite sequence has an open reading frame of 1098 nucleotides encoding a putative presequence of 33 amino acid residues and a mature protein of 333 residues with a calculated M(r) = 36,486. Yeast and human E1 beta exhibit 62% sequence identity. The size of the mRNA is approximately 1.5 kilobases. Hybridization analysis showed that the E1 beta gene (PDH beta 1) is localized to chromosome II. Disruption of PDH beta 1 is not lethal under vegetative growth conditions. The null mutant transformed with PDH beta 1 on a unit-copy plasmid produced mature E1 beta and a functional PDH complex. PMID- 8433987 TI - Autoantibodies to the GLUT-2 glucose transporter of beta cells in insulin dependent diabetes mellitus of recent onset. AB - Purified immunoglobulin G (IgG) from the serum of patients with insulin-dependent diabetes mellitus (IDDM) of recent onset inhibits high-Km uptake of 3-O-methyl beta-D-glucose by rat pancreatic islets. To determine if the inhibition is the result of antibodies against GLUT-2, the high-Km glucose transporter of beta cells, we incubated IDDM sera with rat islet cells and with AtT-20ins cells transfected to express GLUT-2. IDDM sera inhibited glucose uptake in islet cells and in GLUT-2-expressing AtT-20ins cells but not in AtT-20ins cells transfected to express the low-Km isoform, GLUT-1. In 24 of 30 (77%) patients with newly diagnosed IDDM, IgG binding as measured by immunofluorescence and flow cytometry of the cells transfected to express GLUT-2 was > 2 standard deviations from the mean of the nondiabetic population; 29 of 31 (96%) of nondiabetic children were negative (P < 0.0001). Increased IgG binding could be removed by absorption with GLUT-2-expressing cells but not with GLUT-1-expressing cells. We conclude that most patients with IDDM of recent onset have autoantibodies to GLUT-2. PMID- 8433988 TI - A specific membrane binding protein for progesterone in rat brain: sex differences and induction by estrogen. AB - Progesterone conjugated to bovine serum albumin (BSA) was used as a probe to study sex differences and the effects of hormonal status on binding of progesterone to crude synaptosomal membrane preparations (P2) derived from the mediobasal hypothalamic-anterior hypothalamic-preoptic area or the corpus striatum. Binding of 125I-labeled BSA linked to progesterone at the 11 position of the steroid (P-11-BSA) was decreased by competition with unlabeled P-11-BSA or P-3-BSA (in which progesterone is bound to BSA at the 3 position). P-3-BSA displayed higher affinity than P-11-BSA. Hypothalamic and striatal preparations from adult females show high specific binding (60-80%) to the progesterone-BSA conjugate. Specific binding was reduced more than 80% 14 days after ovariectomy. Estrogen treatment (10 micrograms per rat for 4 days) of 14-day ovariectomized rats restored specific binding to levels equivalent to intact females. In contrast, adult males displayed drastically reduced or no specific binding in either tissue. No specific binding was detected after orchidectomy. Estrogen treatment of orchidectomized animals induced specific binding sites similar to those in intact females. Additionally, an affinity probe was developed by linking primary amines on the P-3-BSA conjugate to agarose activated aldehydes in an AminoLink column. A digitoxin-solubilized fraction from female rat P2 cerebellum preparations yielded a single major band after affinity purification with an estimated molecular mass of 40-50 kDa in an SDS/PAGE system after silver stain. These results show a reversible sex difference in the specific binding of progesterone to synaptosomal membrane sites in the central nervous system of male and female rats which is dependent on estrogen. PMID- 8433989 TI - Stimulus-induced association of Ca(2+)-binding proteins with the plasma membrane detected in situ by photolabeling of intact chromaffin and PC12 cells. AB - To investigate the involvement of cytosolic proteins in exocytosis, a system with high temporal and spatial resolution has been developed that allows us to detect the interaction of Ca(2+)- and membrane-binding proteins with the plasma membrane during stimulation of intact chromaffin and PC12 (rat pheochromocytoma) cells. We used 5-iodonaphthalene-1-azide (INA), a hydrophobic label that rapidly partitions into the lipid bilayer of biological membranes. Upon photolysis the label covalently attaches to membrane-embedded domains of proteins. Cells, preincubated with INA in the dark, were stimulated by either 300 microM carbamoylcholine or 60 mM K+ and irradiated (20 s) at various time intervals after stimulation. Subsequently, the cytosolic Ca(2+)- and membrane-binding proteins were isolated in the presence of EGTA (EGTA extract). Of the approximately 40 proteins in the EGTA extract, 15 (15-100 kDa) are labeled in both cell types. Upon stimulation, labeling is increased up to 3-fold in some of the proteins compared to cells labeled under basal conditions. In the absence of external Ca2+, no increase is observed. The rate of label incorporation is similar to the rate of exocytosis in several of these proteins. These results indicate that in the event of triggered exocytosis some of the Ca(2+)-binding proteins interact with the plasma membrane and temporarily embed in the lipid bilayer. Our findings support the hypothesis according to which stimulus-induced alterations in the structure of the Ca(2+) binding proteins lead to their transient insertion into the membrane and thereby to membrane fusion. PMID- 8433990 TI - RuvA and RuvB proteins of Escherichia coli exhibit DNA helicase activity in vitro. AB - The SOS-inducible ruvA and ruvB gene products of Escherichia coli are required for normal levels of genetic recombination and DNA repair. In vitro, RuvA protein interacts specifically with Holliday junctions and, together with RuvB (an ATPase), promotes their movement along DNA. This process, known as branch migration, is important for the formation of heteroduplex DNA. In this paper, we show that the RuvA and RuvB proteins promote the unwinding of partially duplex DNA. Using single-stranded circular DNA substrates with annealed fragments (52 558 nucleotides in length), we show that RuvA and RuvB promote strand displacement with a 5'-->3' polarity. The reaction is ATP-dependent and its efficiency is inversely related to the length of the duplex DNA. These results show that the ruvA and ruvB genes encode a DNA helicase that specifically recognizes Holliday junctions and promotes branch migration. PMID- 8433991 TI - Genetic characterization of six parasitic protozoa: parity between random-primer DNA typing and multilocus enzyme electrophoresis. AB - We have assayed genetic polymorphisms in several species of parasitic protozoa by means of random amplified polymorphic DNA (RAPD). One goal was to ascertain the suitability of RAPD markers for investigating genetic and evolutionary problems, particularly in organisms, such as the parasitic protozoa, unsuitable for traditional methods of genetic analysis. Another goal was to test certain hypotheses concerning Trypanosoma cruzi, and other protozoa, that have been established by multilocus enzyme electrophoresis. The RAPD results corroborate the hypothesis that the population structure of T. cruzi is clonal and yield a phylogeny of the clonal lineages in agreement with the one obtained by enzyme electrophoresis. This parity between the two sets of results confirms that RAPD markers are reliable genetic markers. The RAPD markers are also suitable for reconstructing species phylogenies and as diagnostic characters of species and subspecific lineages. The number of DNA polymorphisms that can be detected by the RAPD method seems virtually unlimited, since the number of primers can be increased effectively at will. The RAPD method is well suited for investigating genetic and evolutionary questions in certain organisms, because it is cost effective and demands no previous genetic knowledge about the organism. PMID- 8433992 TI - ATP-modulated K+ channels sensitive to antidiabetic sulfonylureas are present in adenohypophysis and are involved in growth hormone release. AB - The adenohypophysis contains high-affinity binding sites for antidiabetic sulfonylureas that are specific blockers of ATP-sensitive K+ channels. The binding protein has a M(r) of 145,000 +/- 5000. The presence of ATP-sensitive K+ channels (26 pS) has been demonstrated by electrophysiological techniques. Intracellular perfusion of adenohypophysis cells with an ATP-free medium to activate ATP-sensitive K+ channels induces a large hyperpolarization (approximately 30 mV) that is antagonized by antidiabetic sulfonylureas. Diazoxide opens ATP-sensitive K+ channels in adenohypophysis cells as it does in pancreatic beta cells and also induces a hyperpolarization (approximately 30 mV) that is also suppressed by antidiabetic sulfonylureas. As in pancreatic beta cells, glucose and antidiabetic sulfonylureas depolarize the adenohypophysis cells and thereby indirectly increase Ca2+ influx through L-type Ca2+ channels. The K+ channel opener diazoxide has an opposite effect. Opening ATP-sensitive K+ channels inhibits growth hormone secretion and this inhibition is eliminated by antidiabetic sulfonylureas. PMID- 8433993 TI - Squalamine: an aminosterol antibiotic from the shark. AB - In recent years, a variety of low molecular weight antibiotics have been isolated from diverse animal species. These agents, which include peptides, lipids, and alkaloids, exhibit antibiotic activity against environmental microbes and are thought to play a role in innate immunity. We report here the discovery of a broad-spectrum steroidal antibiotic isolated from tissues of the dogfish shark Squalus acanthias. This water-soluble antibiotic, which we have named squalamine, exhibits potent bactericidal activity against both Gram-negative and Gram positive bacteria. In addition, squalamine is fungicidal and induces osmotic lysis of protozoa. The chemical structure of the antibiotic 3 beta-N-1-(N-[3-(4 aminobutyl)]- 1,3-diaminopropane)-7 alpha,24 zeta-dihydroxy-5 alpha-cholestane 24 sulfate has been determined by fast atom bombardment mass spectroscopy and NMR. Squalamine is a cationic steroid characterized by a condensation of an anionic bile salt intermediate with spermidine. The discovery of squalamine in the shark implicates a steroid as a potential host-defense agent in vertebrates and provides insights into the chemical design of a family of broad-spectrum antibiotics. PMID- 8433994 TI - Evidence for functional interaction between elongation factor Tu and 16S ribosomal RNA. AB - Translation of the genetic code requires the accurate selection of elongation factor (EF)-Tu.GTP.tRNA ternary complexes at the ribosomal acceptor site, or A site. Several independent lines of evidence have implicated the universally conserved 530 loop of 16S rRNA in this process; yet its precise role has not been identified. Using an allele-specific chemical probing strategy, we have examined the functional defect caused by a dominant lethal G-->A substitution at position 530. We find that mutant ribosomes are impaired in EF-Tu-dependent binding of aminoacyl-tRNA in vitro; in contrast, nonenzymatic binding of tRNA to the A and P sites is unaffected, indicating that the defect involves an EF-Tu-related function rather than tRNA-ribosome interactions per se. In vivo, the mutant ribosomes are found in polysomes at low levels and contain reduced amounts of A site-bound tRNA, but normal levels of P-site tRNA, in agreement with the in vitro results; thus the dominant lethal phenotype of mutations at G530 can be explained by impaired interaction of mutant ribosomes with ternary complex. These results provide evidence for a newly defined function of 16S rRNA--namely, modulation of EF-Tu activity during translation. PMID- 8433995 TI - Three-dimensional profiles from residue-pair preferences: identification of sequences with beta/alpha-barrel fold. AB - The three-dimensional profile method expresses the three-dimensional structure of a protein as a table, the profile, which represents the local environment of each residue. The score of an amino acid sequence, aligned with the three-dimensional profile, reflects its compatibility with the profiled structure. In the original implementation, each local environment was characterized by its polarity, the area buried of its side chain, and its secondary structure. Here we describe a modified three-dimensional profile algorithm that characterizes the local environment in terms of the statistical preferences of the profiled residue for neighbors of specific residue types, main-chain conformations, or secondary structure. Combined profiles of the original and the three new types were tested on beta/alpha-barrel protein structures. The method identified the following enzymes of unknown three-dimensional structure as probable beta/alpha-barrels, all of which catalyze reactions in the biosynthesis of aromatic amino acids: anthranilate phosphoribosyltransferase (trpD), glutamine amidotransferase (trpG), and phosphoribosylformimino-5-aminoimidazole carboxamide ribotide isomerase (hisA). PMID- 8433996 TI - Assembly of avian mixed-species flocks in Amazonia. AB - Diamond's "assembly rules" model posits that competitive interactions among species govern the composition of avifaunas. Although originally applied to islands in archipelagoes, this controversial set of hypotheses is difficult to test because islands differ in habitat and resource availability, colonization history, and stochastic effects. Permanent mixed-species flocks of Amazonian birds are a model system for testing the assembly rules hypothesis because flocks occur in relatively homogeneous tracts of rain forest and because resident species are potentially interactive from minute to minute. To analyze cooccurrence patterns of species in flocks, we used null models that incorporate realistic autecological colonization parameters. Potentially competing pairs of congeneric species with similar ecologies cooccur in flocks less often than expected by chance, resulting in perfect checkerboard distributions. Interactions among more distantly related species, however, appear to have little effect on the assembly of mixed-species flocks. Checkerboard distributions enhance local species diversity within habitats by generating different combinations of species in different flocks. This process may have contributed to the immense species richness of the Amazonian avifauna. PMID- 8433997 TI - Formation of large deletions by illegitimate recombination in the HPRT gene of primary human fibroblasts. AB - HPRT gene mutants were isolated from untreated and x-irradiated cultures of primary human fibroblasts, and mutants carrying large deletions were identified. The breakpoints of the deletions were mapped by methods based on the polymerase chain reaction, and the deletion junctions of four different mutants were sequenced. Alu repeats were associated with one end of three of these junctions, but in each case repeat sequences were not found at the other end. Sequence features found at the deletion breakpoints included in particular short direct and inverted repeats, which may mispair to promote illegitimate recombination. One mutant had additional bases inserted at the deletion junction; these bases formed a direct repeat with a sequence immediately adjacent to the junction, suggesting a mechanism of templated repair of broken DNA in deletion formation. PMID- 8433998 TI - Sequence conversion during postreplicative adenovirus overlap recombination. AB - Sequence conversion efficiently transfers genetic information in high yield during postreplicative adenovirus overlap recombination. This process is intrinsically nonreciprocal, depends on adenovirus-specific strand-displacement replication by both partner molecules, and requires that complementary sequences on displaced strands must exceed a minimal length to form a heteroduplex intermediate. PMID- 8433999 TI - Correlation between Src family member regulation by the protein-tyrosine phosphatase CD45 and transmembrane signaling through the T-cell receptor. AB - Stimulation of tyrosine phosphorylation is an early and important event in antigen-induced T-cell activation. T-cell clones deficient in expression of CD45, a transmembrane protein-tyrosine-phosphatase (protein-tyrosine-phosphate phosphohydrolase, EC 3.1.3.48), are impaired in their ability to respond to either antigen or T-cell receptor cross-linking. Analysis of the CD45-deficient CD8+ T-cell clone L3M-93 demonstrates that the Src family members p56lck and p59fyn show increased immunoreactivity with anti-phosphotyrosine antibody and exhibit decreased kinase activity. The site of increased tyrosine phosphorylation in Src family members was identified by comparison of cyanogen bromide peptide maps. Phosphorylation of the C-terminal phosphopeptide, containing the negative regulatory site of tyrosine phosphorylation, from the CD45-deficient cells was increased 8-fold for p56lck and 2-fold for p59fyn. These data suggest that CD45 dephosphorylates the negative regulatory site of multiple Src family members in the cytotoxic T-lymphocyte clone L3 and show a correlation between the ability to respond efficiently to antigen and the dephosphorylation of Src family members by CD45. PMID- 8434000 TI - Telomere-like DNA polymorphisms associated with genetic predisposition to acute myeloid leukemia in irradiated CBA mice. AB - There is evidence that interstitial telomere (TTAGGG)n-like sequences at chromosome 2 fragile sites play an important role in the somatic events that characterize the earliest phases of radiation-induced acute myeloid leukemia in the CBA/H mouse. Here we show that the highly inbred CBA/H colony unexpectedly contains four genotypic variants for telomere-like sequence arrays and that almost all induced myeloid leukemias derive from one of the variant subpopulations that constitutes approximately 20% of the colony. Preliminary evidence on the irregular inheritance patterns for these variant sequences is discussed together with the proposal that one form of these telomere sequence arrays either represents or is closely linked to a locus that influences chromosome 2 breakage patterns in hemopoietic cells following irradiation and, through this, susceptibility to induced myeloid leukemia. PMID- 8434001 TI - Combined use of an immunotoxin and cyclosporine to prevent both activated and quiescent peripheral blood T cells from producing type 1 human immunodeficiency virus. AB - Two different populations of infected T cells are present in human immunodeficiency virus (HIV)-infected individuals: activated cells that produce virions and quiescent cells that harbor the viral genome but are unable to produce virus unless they are activated. Using an in vitro model of acute HIV infection, we have evaluated the effect of depleting activated T cells with an immunotoxin and subsequently inhibiting activation of quiescent T cells with an immunosuppressive agent. CD25 (Tac, p55), the alpha chain of the interleukin 2 receptor, is expressed on activated, but not quiescent, T cells. An anti-CD25 ricin A chain immunotoxin eliminated activated, CD25+ HIV-infected cells and, thereby, inhibited viral production by these cells. Subsequent addition of cyclosporine to the residual CD25- cells prevented their activation and thereby suppressed their ability to produce virus and to propagate the infection to uninfected T cells. PMID- 8434002 TI - Calcium binding proteins distinguish large and small cells of the ventral posterior and lateral geniculate nuclei of the prosimian galago and the tree shrew (Tupaia belangeri). AB - Two different cell types were identified in the thalamus of galago and Tupaia by using antibodies to two calcium binding proteins, calbindin and parvalbumin. In each species studied, the lateral geniculate nucleus consists of six layers, two of which have smaller relay cells. Previous studies have shown that the small cell layers receive fibers from the superior colliculus and project to the superficial layers of the striate cortex. These are the only geniculate layers that react to a calbindin antibody but not parvalbumin. The ventral posterior nucleus was included in the study and the results for both nuclei show that calbindin is a marker for thalamic cells that receive small fibers and project to superficial layers of koniocortex. PMID- 8434003 TI - Nervous system distribution of the serotonin 5-HT3 receptor mRNA. AB - The serotonin 5-HT3 receptor subtype has been implicated in many brain functions. Antagonists of this receptor have anxiolytic and antiemetic effects in humans and in animal models. To determine with cellular resolution the distribution of 5-HT3 receptor mRNA, in situ hybridization was performed in sections of mouse brain and dorsal root ganglia. Scattered labeled cells were observed throughout cortical regions, with highest densities in the piriform, cingulate, and entorhinal areas. Strong hybridization signals were seen in the hippocampal formation, where expression appeared primarily in interneurons. Labeled cells were most abundant in the posteroventral hippocampal region, particularly in the lacunosum moleculare layer of CA1. This distribution suggests that 5-HT3 receptors may mediate the known serotonergic inhibition of pyramidal cell populations via excitation of inhibitory interneurons. Labeled cells were also observed in the major subdivisions of the amygdaloid complex, the olfactory bulb, the trochlear nerve nucleus, the dorsal tegmental region, the facial nerve nucleus, the nucleus of the spinal tract of the trigeminal nerve, and the spinal cord dorsal horn. In the periphery, intense hybridization signals were seen in a subpopulation of cells in dorsal root ganglia. The data correlate generally with physiological, behavioral, and receptor autoradiographic studies, provide cellular resolution, and reveal regions of receptor expression not previously observed. The distribution of 5-HT3 receptor mRNA is consistent with roles for the receptor in cognition and affect and in the modulation of sensory input. PMID- 8434004 TI - Effects of genetic replacements of charged and H-bonding residues in the retinal pocket on Ca2+ binding to deionized bacteriorhodopsin. AB - Metal cations are known to be required for proton pumping by bacteriorhodopsin (bR). Previous studies found that bR has two high-affinity and four to six low affinity Ca(2+)-binding sites. In our efforts to find the location of these Ca2+ sites, the effects of replacing charged (Asp-85, Asp-212, and Arg-82) and H bonding (Tyr-185) residues in the retinal pocket on the color control and binding affinity of Ca2+ ions in Ca(2+)-regenerated bR were examined. The important results are as follows: (i) The removal of Ca2+ from recombinant bR in which charged residues were replaced by neutral ones shifted the retinal absorption to the blue, opposite to that observed in wild-type bR or in recombinant bR in which the H-bonding residue, Tyr-185, was replaced by a non-H-bonding amino acid (Phe). (ii) Similar to the observation in wild-type bR, the binding of Ca2+ to the second site gave the observed color change in the recombinant bR samples in which charged residues were replaced by neutral ones. (iii) The residue replacements had no effect on the affinity constants of the four to six weakly bound Ca2+. (iv) The two high-affinity sites exhibited reduced affinity with substitutions; while the extent of the reduction depended on the specific substitution, each site was reduced by the same factor for each of the charged residue substitutions but by different factors for the mutant where Tyr-185 was replaced with Phe(Y185F). The above results suggest that the two Ca2+ ions in the two high affinity sites are within interaction distance with one another and with the charged residues in the retinal pocket. The results further suggest that, while the interaction between Tyr-185 and the high-affinity Ca2+ ions is relatively short range and specific (with more coupling to the Ca2+ ion in the second affinity site), between the charged residues and Ca2+ ions it seems to be of the electrostatic (e.g., ion-ion) long range, nonspecific type. Although neither Asp 85, Asp-212, nor Arg-82 is individually directly involved in the binding of Ca2+ in these two sites, they might all participate in it. Together with the protonated Schiff base, the charged residues along with Tyr-185 and one or two Ca2+ ions (and probably a few water molecules) seem to form an electrostatically coupled system that is part of a cavity that controls the color and function of bR. PMID- 8434005 TI - Functional specificity of the homeodomain protein fushi tarazu: the role of DNA binding specificity in vivo. AB - The mechanisms determining the functional specificity of Drosophila homeodomain proteins are largely unknown. Here, the role of DNA-binding specificity for the in vivo function of the homeodomain protein fushi tarazu (ftz) is analyzed. We find that specific DNA binding is an important but not sufficient determinant of the functional specificity of ftz in vivo: The ftz DNA-binding specificity mutant ftzQ50K retains partial ftz wild-type activity in gene activation and phenotypic rescue assays. Furthermore, specificity mutations in a ftz-in vivo binding site only partially reduce enhancer activity as compared to null mutations of this site. Despite bicoid-like DNA-binding specificity ftzQ50K does not activate natural or artificial bcd target genes in the realms of ftz. These results are discussed in the light of recent observations on the mechanism of action of the yeast homeodomain protein alpha 2. PMID- 8434006 TI - Identification of C-terminal amino acid residues of cauliflower mosaic virus open reading frame III protein responsible for its DNA binding activity. AB - We cloned in Escherichia coli truncated versions of the protein p15 encoded by open reading frame III of cauliflower mosaic virus. We then compared the ability of the wild-type p15 (129 amino acids) and the deleted p15 to bind viral double stranded DNA genome. Deletions of > 11 amino acids in the C-terminal proline-rich region resulted in loss of DNA binding activity of wild-type p15. Moreover, a point mutation of the proline at position 118 sharply reduced the interaction between the viral protein and DNA. These results suggest that cauliflower mosaic virus p15 belongs to the family of DNA binding proteins having a proline-rich motif involved in interaction with double-stranded DNA. PMID- 8434007 TI - Crystal structure of Escherichia coli L-asparaginase, an enzyme used in cancer therapy. AB - The crystal structure of Escherichia coli asparaginase II (EC 3.5.1.1), a drug (Elspar) used for the treatment of acute lymphoblastic leukemia, has been determined at 2.3 A resolution by using data from a single heavy atom derivative in combination with molecular replacement. The atomic model was refined to an R factor of 0.143. This enzyme, active as a homotetramer with 222 symmetry, belongs to the class of alpha/beta proteins. Each subunit has two domains with unique topological features. On the basis of present structural evidence consistent with previous biochemical studies, we propose locations for the active sites between the N- and C-terminal domains belonging to different subunits and postulate a catalytic role for Thr-89. PMID- 8434008 TI - cDNA cloning of a human mRNA preferentially expressed in hematopoietic cells and with homology to a GDP-dissociation inhibitor for the rho GTP-binding proteins. AB - We have identified the mRNA for a human gene, denoted D4, which is expressed at very high levels in hematopoietic cell lines and in normal cells of lymphoid and myeloid origin. The 1.5-kb transcript is absent or detectable only at low levels in nonhematopoietic tissues. D4 encodes a 201-amino acid protein with homology to rhoGDI, an inhibitor of GDP dissociation for the ras-homologous protein rho. D4 might function also as a regulator of guanine nucleotide exchange for small GTP binding proteins. A homologous transcript of similar size is also preferentially expressed in murine hematopoietic tissues. When totipotent murine embryonic stem cells develop in vitro into hematopoietic cells, the gene is activated with the onset of hematopoiesis. When hematopoietic cell lines are induced to differentiate, the expression of D4 is modulated. Thus, D4 appears to be a developmentally regulated gene. Its preferential expression in hematopoietic cells indicates that D4 likely plays some significant role in the growth and differentiation processes of hematopoietic cells. This significance is underscored by increasing evidence for the involvement of regulators of G proteins in clinical diseases. PMID- 8434009 TI - Using three-color chromosome painting to test chromosome aberration models. AB - Ionizing radiation induces DNA double-strand breaks (DSB), which interact pairwise to produce chromosome aberrations. There have long been two main competing theories of such pairwise DSB-DSB interactions. The "classical" theory asserts that an unrepaired DSB makes two ends that separate within the cell nucleus, with each end subsequently able to join any similar (nontelomeric) end. The "exchange" theory asserts that at a DSB the chromatin does not separate completely; rather the DSB ends remain associated until repair, or an illegitimate recombination involving another DSB, occurs. The DSB-DSB interaction mechanism was tested by using three-color fluorescence in situ hybridization to paint chromosomes and observe "three-color triplets": three broken and misrejoined chromosomes having cyclically permuted colors. We observed 18 "three color triplets" in 2000 cells after 2.25 Gy of gamma-irradiation. On the exchange model in its standard form such three-color triplets cannot occur, so this model is inconsistent with the observations. On the classical model, formalized as a discrete time Markov chain embedded at the transitions of a continuous time Markov chain, the frequency of occurrence of three-color triplets can be computed by Monte Carlo simulations. The number of three-color triplets predicted mathematically by the classical model was found to be slightly larger than the observed number. Thus our data, together with our computer simulations, exclude the standard form of the exchange model but are compatible with the classical model. The results are also compatible with other, more complicated models. PMID- 8434010 TI - Identification of a nonprocessive telomerase activity from mouse cells. AB - Telomerase activity was identified in extracts from several different mouse cell lines. Addition of telomeric TTAGGG repeats was specific to telomeric oligonucleotide primers and sensitive to pretreatment with RNase A. In contrast to the hundreds of repeats synthesized by the human and Tetrahymena telomerase enzymes in vitro, mouse telomerase synthesized only one or two TTAGGG repeats onto telomeric primers. The products observed after elongation of primers with circularly permuted (TTAGGG)3 sequences and after chain termination with ddATP or ddTTP indicated that mouse telomerase pauses after the addition of the first dG residue in the sequence TTAGGG. The short length of the products synthesized by mouse telomerase was not due to a diffusible inhibitor in the mouse extract, because the human telomerase continued to synthesize long products when mixed with mouse fractions. Primer challenge experiments showed that the human enzyme synthesized long TTAGGG repeats processively in vitro, whereas the mouse telomerase appeared to be much less processive. The identification of short telomerase reaction products in mouse extracts suggests that extracts from other organisms may also generate only short products. This knowledge may aid in the identification of telomerase activity in organisms where activity has not yet been detected. PMID- 8434011 TI - Characterization of a host protein associated with brome mosaic virus RNA dependent RNA polymerase. AB - The association of host proteins with viral RNA replication proteins has been reported for a number of (+)-strand RNA viruses. However, little is known about the identity or function of these host proteins in viral replication. In this paper we report the characterization of a host protein associated with the RNA dependent RNA polymerase (RdRp) from brome mosaic virus (BMV)-infected barley. A host protein was specifically and proportionally enriched with BMV RdRp activity through several purification steps. This RdRp-associated host protein reacted with an antiserum prepared against wheat germ eukaryotic translation initiation factor 3 (eIF-3). The RdRp-associated host protein, the p41 subunit of wheat germ eIF-3, and an antigenically related protein from rabbit reticulocyte lysates were all found to bind with high affinity and specificity to BMV-encoded protein 2a, which is involved in viral RNA replication. Moreover, addition of wheat germ eIF 3 or the p41 subunit from wheat germ to BMV RdRp gave a specific and reproducible 3-fold stimulation of (-)-strand RNA synthesis in vivo. These results suggest that the barley analog of eIF-3 subunit p41, or a closely related protein, associates with BMV RdRp in vivo and is involved in BMV RNA replication. This observation and the established role of translation factors in bacteriophage Q beta RdRp suggest that association with translation factors may be a general feature of RNA replication by (+)-strand RNA viruses. PMID- 8434012 TI - Perivascular and intravenous administration of basic fibroblast growth factor: vascular and solid organ deposition. AB - The in vivo mitogenicity of basic fibroblast growth factor (bFGF) for arterial smooth muscle cells relies on the removal of endothelium, raising the question of whether the endothelium serves as a mechanical barrier preventing contact of circulating bFGF with underlying smooth muscle cells or as a biochemical barrier that produces a local inhibitor of bFGF activity. To better define the role of the intact endothelium in modulating the vascular and tissue deposition of bFGF, we compared the fate of intravenous injections of 125I-labeled bFGF with perivascular controlled growth factor release. Peak serum bFGF levels were detected within 1 min of injection, and the growth factor was cleared thereafter with a serum half-life of almost 3 min. Polymeric controlled release devices delivered bFGF to the extravascular space without transendothelial transport. Deposition within the blood vessel wall was rapidly distributed circumferentially and was substantially greater than that observed following intravenous injection. The amount of bFGF deposited in arteries adjacent to the release devices was 40 times that deposited in similar arteries in animals who received a single intravenous bolus of bFGF. Endothelial denudation had a minimal effect on deposition following perivascular release, and it increased deposition following intravenous delivery 2-fold. The presence of intimal hyperplasia increased deposition of perivascularly released bFGF 2.4-fold but decreased the deposition of intravenously injected bFGF by 67%. In contrast, bFGF was 5- to 30-fold more abundant in solid organs after intravenous injection than it was following perivascular release. Deposition was greatest in the kidney, liver, and spleen and was substantially lower in the heart and lung. Thus, bFGF is rapidly cleared following intravenous injection and is deposited within both solid organs and the walls of blood vessels. Unlike the mitogenic potential of bFGF within blood vessels, vascular deposition is virtually independent of the presence of endothelium. Perivascular delivery is far more efficient than intravenous delivery at depositing bFGF within the arterial wall, and an increased neointima may provide added substrate for potential bFGF deposition but has limited contact with intravascular growth factor as a result of dilutional and flow-mediated effects. PMID- 8434013 TI - The short form of the CheA protein restores kinase activity and chemotactic ability to kinase-deficient mutants. AB - Escherichia coli expresses two forms of the chemotaxis-associated CheA protein, CheAL and CheAS, as the result of translational initiation at two distinct, in frame initiation sites in the gene cheA. The long form, CheAL, plays a crucial role in the chemotactic signal transduction mechanism by phosphorylating two other chemotaxis proteins: CheY and CheB. CheAL must first autophosphorylate at amino acid His-48 before transferring its phosphono group to these other signal transduction proteins. The short form, CheAS, lacks the N-terminal 97 amino acids of CheAL and, therefore, does not possess the site of autophosphorylation. Here we demonstrate that although it lacks the ability to autophosphorylate, CheAS can mediate phosphorylation of kinase-deficient variants of CheAL each of which retains a functional autophosphorylation site. This transphosphorylation enables these kinase-deficient CheAL variants to phosphorylate CheY. Because it mediates this activity, CheAS can restore to kinase-deficient E. coli cells the ability to tumble and, thus, to perform chemotaxis in swarm plate assays. PMID- 8434014 TI - Pigment epithelium-derived factor: neurotrophic activity and identification as a member of the serine protease inhibitor gene family. AB - Cultured pigment epithelial cells of the fetal human retina secrete a protein, pigment epithelium-derived factor (PEDF), that induces a neuronal phenotype in cultured human retinoblastoma cells. Morphological changes include the induction of an extensive neurite meshwork and the establishment of corona-like cellular aggregates surrounding a central lumen. The differentiated cells also show increases in the expression of neuron-specific enolase and the 200-kDa neurofilament subunit. Amino acid and DNA sequence data demonstrate that PEDF belongs to the serine protease inhibitor (serpin) family. The PEDF gene contains a typical signal-peptide sequence, initiator methionine codon, and polyadenylylation signal and matches the size of other members of the serpin superfamily (e.g., alpha 1-antitrypsin). It lacks homology, however, at the putative serpin reactive center. Thus, PEDF could exert a paracrine effect in the embryonic retina, influencing neuronal differentiation by a mechanism that does not involve classic inhibition of serine protease activity. PMID- 8434015 TI - A Drosophila photoreceptor cell-specific protein, calphotin, binds calcium and contains a leucine zipper. AB - The calphotin protein, encoded by the calphotin (cap) gene, is expressed in the soma and axons of all Drosophila photoreceptor cells. It is expressed early in photo-receptor cell development, at the time when cell-type decisions are being made. Expression of calphotin is not altered by the glass mutation, which blocks photoreceptor cell development. The calphotin protein binds calcium and contains a long C-terminal leucine zipper. Potential implications of these properties are discussed. PMID- 8434016 TI - Three unusual modifications, a D-arabinosyl, an N-methyl, and a carbamoyl group, are present on the Nod factors of Azorhizobium caulinodans strain ORS571. AB - Azorhizobium caulinodans strain ORS571 is a symbiont of the tropical legume Sesbania rostrata. Upon nod gene induction with naringenin, strain ORS571 secretes into the culture medium Nod factors that morphologically change the host plant--in particular, deformed root hairs (Hai/Had) and meristematic foci are formed at the basis of lateral roots. The latter infrequently develop further into nodule-like structures. The azorhizobial Nod factors are chitin tetramers or pentamers, N-acylated at the nonreducing-end glucosamine with either vaccenic acid (C18:1) or stearic acid (C18:0). They, thus, resemble the previously described Nod factors from (brady)rhizobia. The backbone lipooligosaccharide is substituted with unusual modifications, presumably involved in host-specificity determination. There is a D-arabinose branch on the reducing end and an N-methyl and O-carbamoyl substitution on the nonreducing end of the oligosaccharide chain. The previously identified nod gene nolK may be involved in the synthesis of a D arabinose derivative. The nodS gene product is probably responsible for the N methylation of Nod factors. PMID- 8434017 TI - 5' sequences are important positive and negative determinants of the longevity of Chlamydomonas chloroplast gene transcripts. AB - We have found that sequences in the 5' leader of the Chlamydomonas chloroplast rbcL gene, when fused 5' to foreign genes, destabilize transcripts of these chimeric genes in the chloroplast of transgenic Chlamydomonas but that 5' sequences of the rbcL structural gene prevent this destabilization. Transcripts of the chloroplast rbcL gene are about equally abundant at all times in Chlamydomonas reinhardtii growing on an alternating 12-h light/12-h dark cycle. However, Chlamydomonas chloroplast transformants, harboring chimeric genes containing the same rbcL promoter with 63 or 92 bp of the rbcL 5' leader sequence fused upstream of the Escherichia coli uidA (beta-glucuronidase, GUS) gene, accumulated GUS transcripts only in the dark. Transcripts disappeared rapidly upon illumination of the cells. The same phenomenon was exhibited by transcripts of chimeric genes in which the GUS gene coding sequence was replaced by other unrelated genes. The precipitous light-induced drop in GUS transcript abundance was found to be due to an approximately 16-fold increase in the rate of degradation of GUS transcripts in light rather than to a decrease in the rate of transcription of the GUS gene. Transcripts of a chimeric rbcL-GUS construct in which the leader sequence of the rbcL gene was replaced by 103 bp of the leader sequence of the atpB gene were stable in illuminated cells. The destabilizing effect of the rbcL 5' leader sequence was reversed by adding 257 bp of the 5' coding region of the rbcL gene. The results show that chloroplast transcript levels in illuminated Chlamydomonas cells--and perhaps in other cases--can be determined, at least to some extent, by sequences and interactions of sequences transcribed from the 5' ends of genes. PMID- 8434018 TI - The sulfolipid sulfoquinovosyldiacylglycerol is not required for photosynthetic electron transport in Rhodobacter sphaeroides but enhances growth under phosphate limitation. AB - All photosynthetic organisms, with the exception of several species of photosynthetic bacteria, are thought to contain the sulfolipid 6-sulfo-alpha-D quinovosyldiacylglycerol. The association of this lipid with photosynthetic membranes has led to the assumption that it plays some role in photosynthesis. Stable null mutants of the photosynthetic bacterium Rhodobacter sphaeroides completely lacking sulfolipid were obtained by disruption of the sqdB gene. The ratios of the various components of the photosynthetic electron transport chain, as well as the electron transfer rates during cyclic electron transport, were not altered in the mutants, when grown under optimal conditions. Growth rates of wild type and mutants were identical under a variety of growth conditions, with the exception of phosphate limitation, which resulted in reduced growth of the mutants. Phosphate limitation of the wild type caused a significant reduction in the amount of all phospholipids and an increased amount of sulfolipid. By contrast, the sulfolipid-deficient mutant had reduced levels of phosphatidylcholine and phosphatidylethanolamine but maintained a normal level of phosphatidylglycerol. In addition, two unidentified lipids lacking phosphorus accumulated in the membranes of both wild-type and mutant strains under phosphate limitation. We conclude that sulfolipid plays no significant unique role in photoheterotrophic growth or photosynthetic electron transport in R. sphaeroides but may function as a surrogate for phospholipids, particularly phosphatidylglycerol, under phosphate-limiting conditions. PMID- 8434019 TI - Electrostatic interactions modulate the RNA-binding and transactivation specificities of the human immunodeficiency virus and simian immunodeficiency virus Tat proteins. AB - The transcriptional activating (Tat) proteins from human immunodeficiency virus and simian immunodeficiency virus are sequence-specific RNA-binding proteins. In human immunodeficiency virus Tat, a single arginine residue, flanked on each side by three to four basic amino acids, mediates specific binding to a bulge region in trans-acting responsive element (TAR) RNA. We have systematically mutated the flanking charged residues and found that, in addition to the position of the sequence-specific arginine, the particular arrangement of nonspecific electrostatic interactions is an important determinant of RNA-binding specificity and transactivation activity. These additional electrostatic contacts may help stabilize the structure of TAR RNA when bound to arginine. One critical electrostatic interaction, located two residues N-terminal to the arginine, is absent in the simian immunodeficiency virus Tat protein and accounts for the difference in promoter specificities of the human and simian immunodeficiency viral proteins. PMID- 8434020 TI - In vitro selection of optimal DNA substrates for T4 RNA ligase. AB - We have used in vitro selection techniques to characterize DNA sequences that are ligated efficiently by T4 RNA ligase. We find that the ensemble of selected sequences ligated about 10 times as efficiently as the random mixture of sequences used as the input for selection. Surprisingly, the majority of the selected sequences approximated a well-defined consensus sequence. PMID- 8434021 TI - The activation domain of transcription factor PU.1 binds the retinoblastoma (RB) protein and the transcription factor TFIID in vitro: RB shows sequence similarity to TFIID and TFIIB. AB - The retinoblastoma (RB) tumor suppressor protein and the TATA-box-binding protein TFIID form contacts with a number of viral transactivator proteins. One of these, the adenovirus E1A protein, can bind to both proteins. Here we present evidence that the cellular transcription factor PU.1 can bind to both RB and TFIID. Like E1A, PU.1 binds to the conserved C-terminal domain of TFIID and to the RB "pocket" domain. The PU.1 sequences required to bind either protein lie within a 75-amino acid region which functions as an independent activation domain in vivo. The ability of PU.1 to contact directly both RB and TFIID through the same 75 residue domain prompted us to look for sequence similarity between these two proteins. We find that the previously defined domain A of the RB pocket shows sequence similarity to the conserved C terminus of TFIID, whereas domain B shows sequence similarity to a second general transcription factor, TFIIB. The potential for RB to influence transcription by using TFIID- and TFIIB-related functions is discussed. PMID- 8434023 TI - Oscillatory flow in the cochlea visualized by a magnetic resonance imaging technique. AB - We report a magnetic resonance imaging technique that directly measures motion of cochlear fluids. It uses oscillating magnetic field gradients phase-locked to an external stimulus to selectively visualize and quantify oscillatory fluid motion. It is not invasive, and it does not require optical line-of-sight access to the inner ear. It permits the detection of displacements far smaller than the spatial resolution. The method is demonstrated on a phantom and on living rats. It is projected to have applications for auditory research, for the visualization of vocal tract dynamics during speech and singing, and for determination of the spatial distribution of mechanical relaxations in materials. PMID- 8434022 TI - Regulation of peptide-calmodulin complexes by protein kinase C in vivo. AB - We used the freshwater protozoan Paramecium tetraurelia to investigate the potential regulation by protein kinase C of calmodulin interactions with binding peptides in intact cells. In these organisms, an action potential results in membrane depolarization and a period of backward swimming; repolarization and a return to forward swimming requires the presence of normal calmodulin. We postulated that injection of high-affinity calmodulin binding peptides might interfere with repolarization and thus prolong the period of membrane depolarization. Synthetic peptides spanning the protein kinase C phosphorylation site/calmodulin-binding domains of the myristoylated alanine-rich C-kinase substrate (MARCKS) and the MARCKS-related protein (also known as F52 or MacMARCKS) were injected into cells; these caused a 2- to 3-fold increase in the duration of backward swimming. Similar changes were seen with two other calmodulin-binding peptides. This behavioral response could be prevented by coinjecting calmodulin. Activation of Paramecium protein kinase C with an active phorbol ester completely reversed (within 3 min) the behavioral effects of the normal MARCKS and MARCKS-related protein peptides. Injection of a nonphosphorylatable peptide, in which alanines were substituted for serines, resulted in the usual behavioral response; however, this was not reversed by phorbol ester treatment. The corresponding aspartate-substituted peptide, which has a 10-fold lower affinity for calmodulin, did not prolong backward swimming. These data suggest that these peptides can form complexes with calmodulin at the calcium concentrations that prevail in intact Paramecium cells and that such complexes can be disrupted by protein kinase C phosphorylation of the peptides. PMID- 8434024 TI - Stimulation of human thyroid growth via the inhibitory guanine nucleotide binding (G) protein Gi: constitutive expression of the G-protein alpha subunit Gi alpha-1 in autonomous adenoma. AB - The alpha subunits of the stimulatory and inhibitory G proteins, Gs alpha and Gi alpha, activate transmembrane-signaling systems involved in the control of cell proliferation. We have investigated the pattern of expression of Gi alpha subtypes and Gi alpha-mediated proliferative responses in the human thyroid. Human thyroid membranes contain two subtypes of Gi alpha, Gi alpha-1 and Gi alpha 2, as assessed by using specific antibodies. The expression of Gi alpha-1 is under tight control by thyrotropin in vivo and in primary cultures of thyroid epithelial cells. In contrast, Gi alpha-1 is expressed in the absence of thyrotropin in thyroid autonomous adenoma, an endocrine-active tumor, and its levels are not regulated by thyrotropin in thyroid epithelial cells prepared from these tumors. If thyroid epithelial cells are treated with pertussis toxin to block signal transduction via Gi, the mitogenic response to serum factors is reduced. These observations demonstrate that Gi subtypes transmit growth stimuli in the human thyroid. The constitutive expression of Gi alpha-1 in autonomous adenoma may allow for the unregulated stimulation of thyroid cell proliferation by a yet unidentified signaling pathway and, thus, be causally related to autonomous growth of thyroid cells. PMID- 8434025 TI - DNA repair and aging in basal cell carcinoma: a molecular epidemiology study. AB - This molecular epidemiology study examines the DNA-repair capacities (DRCs) of basal cell carcinoma (BCC) skin cancer patients (88) and their controls (135) by using a plasmid/host-cell reactivation assay. In this assay UV-damaged expression vector plasmid is transfected into peripheral blood T lymphocytes from the subjects. The host-cellular repair enzymes repair the photochemical damage in the plasmid, and 40 hr later the plasmid-encoded reporter chloramphenicol acetyltransferase is measured. An age-related decline in this DRC, amounting to approximately 0.61% per yr occurred in the controls from 20 to 60 yr of age. Reduced DRC was a particularly important risk factor for young individuals with BCC and for those individuals with a family history of skin cancer. Young individuals with BCC repaired DNA damage poorly when compared with controls. As the BCC patients aged, however, differences between cases and controls gradually disappeared. The normal decline in DNA repair with increased age may account for the increased risk of skin cancer that begins in middle age, suggesting that the occurrence of skin cancer in the young may represent precocious aging. Patients with reduced DRCs and overexposure to sunlight had an estimated risk of BCC > 5 fold greater than the control group. Such a risk was even greater (10-fold) in female subjects. PMID- 8434026 TI - Increased resistance to oxidative stress in transgenic plants that overexpress chloroplastic Cu/Zn superoxide dismutase. AB - Transgenic tobacco plants that express a chimeric gene that encodes chloroplast localized Cu/Zn superoxide dismutase (SOD) from pea have been developed. To investigate whether increased expression of chloroplast-targeted SOD could alter the resistance of photosynthesis to environmental stress, these plants were subjected to chilling temperatures and moderate (500 mumol of quanta per m2 per s) or high (1500 mumol of quanta per m2 per s) light intensity. During exposure to moderate stress, transgenic SOD plants retained rates of photosynthesis approximately 20% higher than untransformed tobacco plants, implicating active oxygen species in the reduction of photosynthesis during chilling. Unlike untransformed plants, transgenic SOD plants were capable of maintaining nearly 90% of their photosynthetic capacity (determined by their photosynthetic rates at 25 degrees C) following exposure to chilling at high light intensity for 4 hr. These plants also showed reduced levels of light-mediated cellular damage from the superoxide-generating herbicide methyl viologen. These results demonstrate that SOD is a critical component of the active-oxygen-scavenging system of plant chloroplasts and indicate that modification of SOD expression in transgenic plants can improve plant stress tolerance. PMID- 8434027 TI - Characterization of bovine ovary angiotensin II receptors using subtype-selective antagonists. AB - Angiotensin-II (AII) receptors have been classified as AT1 and AT2 subtypes based on selective antagonists. AII binding sites in bovine ovary membranes were characterized using the radiolabeled AII antagonist, [125I]Sar1,Ile8-AII ([125I]SIA). The binding was specific and saturable with dissociation constant (Kd) and maximum binding (Bmax) of 0.18 +/- 0.08 nmol/l and 32.5 +/- 1.3 fmol/mg, respectively. Pretreatment of ovarian membranes with dithiothreitol (10 mumol/l) doubled the specific binding of [125I]SIA twofold to 63.5 +/- 2.8 fmol/mg. Guanine nucleotide had no significant effect on the affinity of agonist (AII) to compete for [125I]SIA binding. AII and a series of AII-related analogs were used in competition binding experiments, and the data were compared with those obtained with membranes prepared from bovine adrenal cortex and bovine cerebellum. The membranes from ovary and cerebellum showed similar binding characteristics, but they differed from those of adrenal cortex. CGP42112A and WL 19, AT2-subtype selective antagonists, inhibited [125I]SIA binding to ovarian membrane with IC50 values of 28 +/- 4 and 26.7 +/- 2.8 nmol/l, respectively. SK&F 108566 and DuP 753, AT1-subtype-selective antagonists, had very little effect on [125I]SIA binding to ovarian membranes. These data directly demonstrate that bovine ovary membranes have predominantly AT2-subtype AII receptors. PMID- 8434028 TI - RG 12561 (dalvastatin): a novel synthetic inhibitor of HMG-CoA reductase and cholesterol-lowering agent. AB - RG 12561 (dalvastatin) is a prodrug which converts to its open hydroxyacid form in the body. The Na salt of RG 12561 (RG 12561-Na) is a potent inhibitor of 3 hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in the cholesterol biosynthetic pathway. It competitively inhibits rat liver HMG-CoA reductase with an IC50 value of 3.4 nmol/l. In the same assay, the IC50 values for other potent HMG-CoA reductase inhibitors, lovastatin-Na and pravastatin, were 2.3 and 8.9 nmol/l, respectively. In Hep G2 liver cells, RG 12561-Na, lovastatin-Na and pravastatin inhibited cholesterol biosynthesis from radiolabeled octanoate with IC50 values of 4 and 5 nmol/l and 1.1 mumol/l, respectively. In a rat ex vivo assay, orally administered RG 12561, lovastatin and pravastatin inhibited cholesterol biosynthesis in liver slices with ED50 values of 0.9, 0.5 and 12 mg/kg, respectively. In cholestyramine-fed hamsters, RG 12561 (0.1% in food for 18 days) reduced LDL cholesterol, whereas HDL was slightly increased. The reductions in the LDL/HDL ratio for RG 12561, RG 12561 Na, lovastatin and lovastatin-Na were 35, 76, 88 and 88%, respectively. At a higher dose, RG 12561 (0.4% in food) reduced serum cholesterol, LDL and LDL/HDL by 84, 97 and 91%, respectively. In WHHL rabbits, RG 12561 and lovastatin (5 mg/kg, b.i.d., 12 days) reduced serum cholesterol by 17 and 16%, respectively. These results demonstrate that RG 12561 is a potent cholesterol-lowering agent. PMID- 8434029 TI - Absence of relationship between antiarrhythmic effects of antidepressant drugs and lipid peroxidation. AB - Tricyclic antidepressant drugs may affect the cardiovascular system, principally in patients with preexisting cardiac disease. The present study was undertaken to compare the effects of amitriptyline and mianserin with those of tianeptine, an atypical tricyclic antidepressant drug, in rat isolated working heart subjected to a local myocardial ischemia. Coronary, aortic and cardiac flows, and heart rate remained stable during the whole preischemic period in control hearts. Ligation of the left main coronary artery induced a 50% decrease in coronary, aortic and cardiac flow without any change in heart rate. Reperfusion was characterized by the occurrence of ventricular arrhythmias (ventricular tachycardia and ventricular fibrillation) and by a marked reduction in cardiodynamic parameters. Amitriptyline (1 and 10 mumol/l) and mianserin (1 and 10 mumol/l) exhibited an antiarrhythmic activity against reperfusion arrhythmias. Tianeptine (1 and 10 mumol/l) was not able to reduce the incidence of reperfusion arrhythmias. Although tianeptine did not change heart rate, mianserin and amitriptyline induced a bradycardia. Mianserin and amitriptyline improved the cardiac recovery of cardiac function during reperfusion. The cardiodynamic parameters (coronary, aortic and cardiac flows) were not altered by tianeptine during the preischemic period. Furthermore, these parameters were similar to those observed in the control group both during ischemia and reperfusion. The beneficial effects of amitriptyline and mianserin observed in the setting of myocardial reperfusion were not associated with a reduced lipoperoxidation investigated by using an in vitro model in the presence or absence of a free radical-generating system. The results of the present study indicate that the pronounced antiarrhythmic activities of mianserin and amitriptyline cannot be explained by an antiperoxidative action of these drugs. PMID- 8434030 TI - Carnitine action on neuromuscular disturbances in the fasting rat: potentiation by L-lysine. AB - L-Carnitine (oral route) significantly corrects the muscle hypocontractility and hypoexcitability induced in the rat after 5 consecutive days of fasting. This effect is interpreted on the basis of the dual role of L-carnitine as cofactor in the transport of long-chain fatty acids into the mitochondria and as a detoxifying agent of intracellular acyl-CoA. The activity of L-carnitine is increased with the concomitant administration (oral route) of an equimolar dose of L-lysine. In the present experimental conditions, there is a threefold potentiation by comparison with L-carnitine alone. This result is discussed on the basis of the combined effects of an exogenous supply of L-carnitine and endogenous synthesis of L-carnitine from the L-lysine administered at the same time. PMID- 8434031 TI - Iterative stimulation of pancreatic islets by glipizide. AB - Iterative administrations of glipizide (2 mumol/l) for 10 min each to perifused rat pancreatic islets provoked at low glucose concentration (2.8 mmol/l) rapid and rapidly reversible decreases in 86Rb outflow, rapid and rapidly reversible increases in 45Ca outflow and modest stimulations of insulin release. In the presence of Ca2+, the reascension in 86Rb outflow was preceded by a transient fall in effluent radioactivity upon withdrawal of the sulfonylurea. At a higher concentration of D-glucose (8.3 mmol/l), glipizide provoked, each time, biphasic and rapidly reversible increases in both 86Rb and 45Ca outflow, as well as in insulin release. These results are compatible with the view that glipizide decreases K+ conductance, leading to depolarization of the B-cell plasma membrane and gating of voltage-sensitive Ca2+ channels. In the presence of 8.3 mmol/l D glucose, however, the inhibitory effect of glipizide on effluent K+ permeability may be masked by activation of Ca(2+)-sensitive K+ channels. The present data also indicate that glipizide is able to evoke, at the occasion of iterative administrations, biphasic ionic and secretory responses, without evidence of tachyphylaxis. PMID- 8434033 TI - Crumbs of one man's life: Dr. Dolittle remembered. PMID- 8434034 TI - Notes from the pit: two vignettes. PMID- 8434032 TI - Effect of age and cinnarizine treatment on brain dopamine receptors. AB - The density and distribution of dopamine D1 and D2 receptors visualized by in vitro autoradiography were investigated in adult and senescent BL C57 mice. A significant decrease was observed in regions of the basal ganglia of senescent animals, which was more pronounced for the D1 subtype. Chronic treatment with cinnarizine, an organic Ca2+ channel antagonist, alters both D1 and D2 receptor densities, with a higher sensitivity of the D1 subtype. These results could indicate that the interactions between dopamine receptor subtypes may be necessary for the full expression of behavioral events mediated by the D2 receptors. PMID- 8434035 TI - Chaos in health care. PMID- 8434036 TI - Transplantation and the end-stage renal disease program. PMID- 8434037 TI - An early call for health care reform: the committee of 430 physicians. PMID- 8434038 TI - The mind-body problem in the twentieth century, and La Mettrie. PMID- 8434039 TI - Laughing at breast cancer: a commentary. PMID- 8434041 TI - Dear doctor. PMID- 8434040 TI - Handle with care: is it really child abuse? PMID- 8434042 TI - Health care concerns: a call for action. PMID- 8434043 TI - Questions and reflections. One life saved. PMID- 8434044 TI - Thoughts about IT. PMID- 8434045 TI - Past and present. Closing the circle on the right to die. PMID- 8434046 TI - Altruism in medicine: prescription for the nineties. PMID- 8434047 TI - Ginsenoside Rg1 prevents histaminergic modulation of rat adaptive behavior from elevation of ambient temperature. AB - Effects of ginsenoside Rg1 (Rg1) on histaminergic modulation of both adaptive behavior and thermoregulation were investigated at high ambient temperature. Continuous infusion of Rg1 using an osmotic minipump into the rat third cerebroventricle attenuated anorexia induced by elevation of ambient temperature from 21 degrees C to 31 degrees C. Intraperitoneal injection of alpha fluoromethylhistidine (FMH), a specific suicide inhibitor of a histamine synthesizing decarboxylase enzyme, also prevented the anorexia induced by elevated temperature. The ratio of water intake to food intake, which showed no change on the first day after elevation of room temperature, was not influenced by treatment of either FMH or Rg1. Rectal temperature, which was normally maintained at a constant level even after shifting ambient temperature from 21 degrees C to 31 degrees C, elevated after FMH treatment. The Rg1 infusion, however, maintained rectal temperature normally at 31 degrees C. Hypothalamic histamine content increased in response to elevation of ambient temperature. The Rg1 infusion maintained constant histamine level against elevation of environmental temperature. Under the heated condition FMH reduced hypothalamic histamine. These findings suggest that Rg1 may modulate rat adaptive behavior by blockade of temperature-related information into the hypothalamic histamine neurons. PMID- 8434048 TI - Self-selection of ascorbic acid in coloured foods by heat-stressed broiler chicks. AB - Female broiler chicks were given red and green supplemented (200 mg ascorbic acid (AA)/kg) and unsupplemented foods on alternate days for 8 days under heat stressed and unstressed conditions. After this training period, the birds were given access to both foods, and the intake of each was monitored. In both heated treatments the intake of the supplemented food was significantly higher (p < 0.05) than of the unsupplemented food (800 vs. 518 g/14 days), although in the unheated groups significantly more of the unsupplemented food was eaten (756 vs. 639 g/14 days). Birds were unable to select for AA when neither food was coloured, even when they were presented continuously in the same positions in the cage. It is concluded that chicks can learn to associate the colour of the food with its AA content and that they select proportions of supplemented and unsupplemented foods appropriate for their needs, as influenced by environmental temperature. PMID- 8434049 TI - Effect of the TRH analogue, CG 3703, on prolactin secretion in the pseudopregnant rat. AB - The effect of the TRH analogue, CG 3703 (AG), on secretion of prolactin (Prl) was studied in pseudopregnant rats. AG stimulated Prl secretion of incubated pituitary glands in the presence of 5.10(-8) M dopamine (DA) but not in the presence of 0 or 10(-6) M DA. AG did not inhibit the in vitro secretion of Prl. AG postponed the peaks of Prl which were generated between 0100 and 1200 h (delay after 500 micrograms AG: 3-4 h); the height of these nocturnal Prl peaks was not affected by AG. AG did not induce Prl secretion during the phase of low Prl secretion (the interphase) between 2000 and 0100 h. The DA-release blocking drug, HA 966, induced peaks of Prl during the interphase. These peaks were as high as spontaneous nocturnal Prl peaks and were blocked by AG. The results show that AG has two opposite effects on Prl secretion: a direct, stimulating effect, which is modulated by DA, and an indirect inhibitory effect, which is probably executed by DA, released by AG from the tuberoinfundibular DA neurons. PMID- 8434050 TI - P300, habituation, and response mode. AB - The P3(00) event-related brain potential (ERP) was elicited with an auditory discrimination paradigm under two response task conditions in which the probability of the target tone was always 0.20. Subjects either counted the occurrence of each target tone or pressed a button to the target in different conditions. No response was made to the standard tone. Consecutive blocks of trials were obtained to assess habituation of P3 amplitude. The count task demonstrated less habituation than the button-press task, with a strong interaction obtained between response mode and trial block for all electrode sites. The findings suggest that habituation of P3 amplitude is sensitive to the amount of attentional resources allocated to the processing of a target stimulus, with more resources required for a count task compared to fewer needed for a button-press response. PMID- 8434051 TI - Circadian rhythms during gradually delaying and advancing sleep and light schedules. AB - The circadian rhythms of the night shift worker show very little phase shift in response to the daytime sleep and night work schedule. One strategy for producing circadian adaptation may be to use appropriately timed exposure to high-intensity light. We attempted to shift the circadian temperature rhythms of seven normal subjects while they followed a sleep schedule that gradually delayed (2 h per day) until sleep occurred during the daytime, as is customary for workers during the night shift. After 5 days, the sleep schedule was gradually advanced back to baseline. High illuminance light (2 h per day) and the attenuation or avoidance of sunlight were timed to facilitate temperature rhythm phase shifts. In general, the temperature rhythm did not shift along with the sleep-wake schedule, but appeared either to free run or remain entrained to the natural 24-h zeitgebers. This study showed how difficult it can be to shift human circadian rhythms in the field, when subjects are exposed to competing 24-hr zeitgebers. PMID- 8434052 TI - Central and peripheral prostaglandins are involved in sickness behavior in birds. AB - Many of the behavioral manifestations of mammals and birds following infection are now recognized as important mechanisms for maintaining homeostasis and promoting recovery. To investigate the role of prostaglandins (PGs) in the behavioral and physiological effects of lipopolysaccharide (LPS) in birds, chickens were injected with indomethacin (Ind) peripherally (IP, 5 mg) or centrally (ICV, 100 micrograms) and their behavior and body temperature following a challenge IP injection of LPS (2.5 mg) were assessed at 1 and 2 h, respectively. Pretreatment with Ind IP or ICV completely inhibited the hyperthermia caused by LPS. Ind injected IP but not ICV significantly attenuated the LPS-induced anorexia. The drowsiness caused by LPS was completely inhibited by Ind injected IP and partially inhibited by Ind administered ICV. These results are interpreted to indicate that LPS induces hyperthermia in the chicken by activating a PG system in the brain. Peripheral PGs appear to be involved in the anorectic response to LPS, whereas drowsiness caused by LPS may involve both peripheral and central PGs. These data are consistent with the hypothesis that multiple PG systems are activated during the acute-phase response, which may explain the dissociation between mechanisms controlling the behavioral and physiological responses to infection. PMID- 8434053 TI - Restrained and nonrestrained eaters' orienting responses to food and nonfood odors. AB - Dietary restraint was assessed by Stunkard and Messick's (1985) three-factor eating questionnaire, using the restraint subfactor score only in normal-weight college students (n = 41). The subjects were than assessed for skin conductance orienting responses (ORs) to food and nonfood odors when hungry and sated (after a standard breakfast and after an overnight fast). Subjects also rated their hunger and each odorant for pleasantness on separate 7-point scales. Results indicated that restrained eaters oriented less to odors than did nonrestrained subjects. Food deprivation did not differentially affect the ORs in restrained and nonrestrained eaters. The ORs, however, tended to be decreased in all of subjects who had had breakfast. Finally, nonrestrained subjects rated food and nonfood odors approximately equal in pleasantness, while the restrained eaters rated food odors as more pleasant than the nonfood odors. These results suggest that restrained eaters must certainly process odor stimuli related to foods, but also suggests that orienting to these salient (informative) cues is restricted. Perhaps in defense of the diet, restrained eaters learn methods/responses (cognitive strategies, instructional sets) to block orienting to food related cues such as odors. PMID- 8434054 TI - Visual memory and visual spatial functions in the rat following parietal and temporal cortex injuries. AB - Adult rats were prepared with either posterior parietal, temporal, or sham neocortical lesions, and after assessing gross locomotor functions, trained in cognitive visual tasks. Training was conducted in a modified circular water maze wherein the water was made opaque with a white nontoxic powder paint. The order of the tasks was counterbalanced within groups. One task was a visual matching-to sample problem with an intertrial interval of 20 s. The second task was a visual spatial conditional problem in which visual stimuli (white or gray cards) cued spatial choices in a T maze that was inserted into the tank. After completing these tasks, the animals were trained on a simple visual pattern discrimination and a simple position habit. Both lesion groups demonstrated significant deficits on both cognitive tasks. Since gross visual perceptual, spatial, and motor abilities were found to be unaffected by the lesions, it is suggested that a generalized retardation in cognitive functions follows injuries in these sites. Also, qualitative evidence supported the conclusion that posterior parietal cortex plays an important role in integrating visuospatial stimuli with motor responses. PMID- 8434055 TI - Effects of illumination on human nocturnal serum melatonin levels and performance. AB - In humans, exposure to bright light at night suppresses the normal nocturnal elevation in circulating melatonin. Oral administration of pharmacological doses of melatonin during the day, when melatonin levels are normally minimal, induces fatigue. To examine the relationship between illumination, human pineal function, and behavior, we monitored the overnight serum melatonin profiles and behavioral performance of 24 healthy male subjects. On each of three separate occasions subjects participated in 13.5 h (1630-0800 h) testing sessions. Each subject was assigned to an individually illuminated workstation that was maintained throughout the night at an illumination level of approximately 300, 1500, or 3000 lux. Melatonin levels were significantly diminished by light treatment, F(2, 36) = 12.77, p < 0.001, in a dose-dependent manner. Performance on vigilance, reaction time, and other tasks deteriorated throughout the night, consistent with known circadian variations in these parameters, but independent of ambient light intensity and circulating melatonin levels. PMID- 8434056 TI - Further evidence that prolactin secretion in adult female rats is differently modified after neonatal estrogenization or androgenization: responses to methysergide, quipazine, and pizotifen. AB - The role of the serotoninergic system in the control of prolactin secretion was investigated in adult female rats treated on the first day of life with estradiol benzoate (EB) (100 micrograms), testosterone propionate (TP) (25 or 100 micrograms), or olive oil. Blood of rats was obtained through a chronic intraatrial cannula at 0, 30, 60, 90, and 120 min after the IP administration of the serotoninergic blockers methysergide (0.75, 2.5, and 7.5 mg/kg) or pizotifen (2 mg/kg), the agonist quipazine (3 or 30 mg/kg), or saline. We have found that 1) the anovulatory syndrome induced by EB or 100 micrograms injection of TP was associated with hyperprolactinaemia, whereas normal prolactin concentrations in plasma were observed in females injected with 25 micrograms of TP; 2) methysergide administration increased plasma prolactin concentrations in control and androgenized females but not in the estrogenized ones. This different response may be related to the antidopaminergic action of methysergide, because both estrogenized and androgenized females responded similarly after pizotifen injection; 3) after quipazine injection, an initial stimulation was observed in females injected with estradiol or 100 micrograms of TP, but not in other groups, whereas a delayed inhibition occurred in androgenized females. These results suggest that the effects of estrogenization and androgenization on both the dopaminergic and serotoninergic control of prolactin secretion are qualitatively different. PMID- 8434057 TI - Early onset of reduced morphine analgesia by ingestion of sweet solutions. AB - Morphine analgesia can be reduced by prior exposure to food and flavored fluids. The early onset of reduced morphine-induced analgesia (RMA) was studied in 82 male Wistar rats after allowing them access to either a dextrose-saccharin solution or unflavored tap water for 6 or 3 h (Experiment 1, n = 40) or for 3 h, 90, or 45 min (Experiment 2, n = 42). Morphine (4 mg/kg) was injected subcutaneously at the end of the drinking period, and after 25 min a series of tail flick tests was conducted. Morphine produced strong analgesia in all rats that drank unflavored tap water; however, in rats that drank the flavored solution, the analgesic effect of morphine was significantly attenuated following exposures of 6 or 3 h, but not following exposures of 90 or 45 min. Similar quantities of flavored fluid were consumed by groups at all exposure durations; thus, RMA was determined by duration of exposure and not amount consumed. No analgesia attributable to flavor consumption per se was observed. The results suggest that RMA is mediated by endogenous opioid activity in the gustatory and analgesic systems by a mechanism akin to tolerance that requires about 3 h to operate. PMID- 8434058 TI - Olfactory dysfunction in diabetes mellitus. AB - Olfactory dysfunction has been reported in individuals with diabetes mellitus, but the etiology is unknown. Diabetes is often complicated by serious medical conditions which could be related to the development of decreased olfactory ability. Overall, our 111 subjects with diabetes showed deficiencies in their ability to identify odorants measured with the Odorant Confusion Matrix (mean = 67.8% correct). The presence of macrovascular disease was found to be associated with olfactory dysfunction. Glycemic control as well as the type and duration of diabetes were not related to olfactory ability. Also, there was no distinct association with the presence of neuropathy, retinopathy, nephropathy, hypertension, or impotence. Consistent with previous studies utilizing measures of odorant identification, performance decreased with increased age, females were somewhat superior to males, and smoking had a deleterious effect. Other nondiabetes-related medical conditions and medications had no apparent effect on the olfactory ability of our subjects. These results suggest that the sequelae associated with macrovascular disease, such as perhaps, ischemia, to the olfactory area, impact negatively on olfactory ability. PMID- 8434059 TI - Effects of cerebellectomy on motivation-related behavior: a time-course study. AB - The open field behavior and learning capacity of male rats of the Wistar strain was studied 1, 2, and 6 months after cerebellectomy (CBX). The results show a decrease in locomotor activity 1 month after CBX and thereafter a slow recovery. Grooming behavior was still normal after 1 month, but it decreased 2 months after CBX. Learning capacity, as assessed by the shuttle-box test, was remarkably decreased in cerebellectomized animals 1 month after operation. A significant impairment of memory capacity was also observed in rats tested for passive avoidance behavior 2 months after CBX. A partial recovery of this parameter was present 6 months after operation. These results support the hypothesis of a possible influence of cerebellum on motivation-related behaviors, independently of its modulatory role on motricity. PMID- 8434060 TI - Scheduled feeding caused activation of dopamine metabolism in the striatum of rats. AB - The effects of a time-restricted feeding schedule on dopamine (DA) release and its metabolites output in the striatum of freely moving rats were studied. Rats had access to food for only 2 h daily for 7 successive days. On the 1st or 7th day, the extracellular concentrations of DA, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the ventrolateral striatum were measured by in vivo brain microdialysis during 2 h of exposure to food-related stimuli followed by 2 h of access to food. Extracellular concentrations of DA and its metabolites did not change during the period of exposure to food-related stimuli or during feeding on the 1st day. On the 7th day, extracellular DOPAC and HVA concentrations increased significantly during 2 h of feeding, but not during exposure to food-related stimuli, compared with basal levels. Extracellular DA concentration did not change significantly. These results indicate that scheduled feeding caused activation of DA metabolism in the ventrolateral striatum and facilitate feeding-related motor activity in feeding behavior. PMID- 8434061 TI - Responses to isolation in Japanese quail genetically selected for high or low sociality. AB - The adrenocortical, behavioral, and leucocytic responses to isolation, for 1, 3, or 72 h, of 7-10-day-old Japanese quail chicks, of lines selected for high (HSR) or low (LSR) levels of social reinstatement (SR) behavior, were studied. Isolation had no effect on plasma corticosterone levels of heterophil/lymphocyte measures in LSR line chicks. Conversely, circulating corticosterone levels were increased after 1 h of isolation in the HSR line, although they fell to control levels thereafter. Heterophil/lymphocyte ratios of HSR line chicks were also increased after 3 h of isolation but decreased to control levels thereafter. Isolated HSR line chicks were consistently more active and showed more peeping and jumping than LSR line chicks in which sitting and lying were more frequent. However, no such behavioral divergence was observed when HSR and LSR line chicks were housed in same-line groups. These results indicate that selection for SR behavior has influenced both underlying social motivation and responses to short term isolation. Social separation appeared to be more stressful for HSR than LSR line chicks. PMID- 8434062 TI - Visual-spatial functions persist following temporal and posterior parietal cortex lesions in rat. AB - Adult rats were prepared with either posterior parietal, temporal, or sham neocortical lesions. Gross kinetic functions and equilibrium were assessed on alternate days for 12 days following surgery by placing the animal on an elevated rod (3.5 cm diameter) oriented 20 degrees to horizontal and rating locomotor functions. Although all groups improved with experience and time postsurgery, rats with posterior parietal lesions exhibited a greater kinetic disturbance throughout the testing period. After a 3-week recovery period, the animals were trained on a visual-spatial task in which a visual stimulus located at the choice point cued whether the escape platform was located in the left or right arm of a T-maze. Animals were trained at a rate of 20 trials per day until a criterion of 18 correct responses in a series of 20 trials was observed. This task differed from that used in a similar previous study in this laboratory (1) in that stimulus saliency was increased and rats were punished for errors by confinement to the incorrect alley for 15 s when errors were made. All rats learned the task, and although there were subtle differences in the rate of acquisition between the groups, there were no gross differences on any of several measures of learning and performance. It is concluded that, under appropriate conditions, rats with injuries in these posterior association regions can learn and perform a task requiring the execution of different spatial responses on the basis of visual landmark cues that are spatially discontiguous from the escape site. PMID- 8434063 TI - Individual, phase, and weekly variations in daily cycles of wrist activity in freeliving humans. AB - Wrist activity was monitored in 17 college students for 11-15 days each. Records of individuals had distinctive patterns, like fingerprints. The subjects all exhibited daily cycles in their activity with activity during the daytime and with period lengths close to 24 h. There was individual variation in average phase (onset 5.3 h, offset 4.5 h, acrophase 6.1 h). Individual subjects all showed 7-day oscillations in their activity patterns associated with the weekly work-leisure schedules. During the leisure weekends, the subjects as a group had a 2.1-h delay in onset, a 1.5-h delay in acrophase, and a 0.8-h shortening in alpha. PMID- 8434064 TI - A method for third ventricular cannulation of small passerine birds. AB - This paper describes a method for chronically cannulating the third ventricle of the white-crowned sparrow, a small passerine bird, without damaging the midsagittal sinus. The method is reliable and chronic over at least 1 month. The technique was verified by assessing the effects of angiotensin II (ANG II) on inducing drinking behavior. All birds rapidly recovered from the surgery and tolerated repeated injections spaced over 1 month. Animals were injected with saline or 0.01, 0.5, 1.0, and 10.0 micrograms of ANG II, respectively. The intermediate dose of 1.0 microgram was maximally effective and caused a significant increase of water intake over the test hour. Lower and higher doses were less effective. This method for cannulating the third ventricle of small passerine birds should prove beneficial in future neurobiological applications. PMID- 8434065 TI - Circadian activity rhythms in SHR and WKY rats: strain differences and effects of clonidine. AB - The spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) inbred rat strains have been subjected to extensive behavioral and neurochemical characterization. The present study examined free-running circadian activity rhythms in these two strains. Because previous studies indicated that free running rhythms are altered during chronic clonidine administration, and that SHRs and WKYs may respond differentially to clonidine, the effects of this agent on rhythmicity were compared in the two strains. SHRs were hyperactive and showed shorter free-running periods than did WKYs. Clonidine administration altered free running rhythms similarly in the two strains, but reduced activity levels only in the relatively hyperactive SHRs. These results are consistent with the hypothesis that central noradrenergic systems influence circadian locomotor activity rhythms. PMID- 8434066 TI - Forestomach motility and behavior of bull calves according to changes in regimen. AB - Six 23-week-old bull calves were randomly assigned to a crossover design to study the effects of hay and concentrates given separately (A), silage and concentrates given in complete mixed ration (B), or given separately (C) on reticulo-ruminal motility and eating and resting behaviors after an adaptation period of 14 days (day 14). The effects of a change from one treatment to another on the same variables were also investigated (day 1). The differences observed between day 1 and day 14 indicate that a change in regimen, even not drastic, seems to affect reticulo-ruminal motility, rumination pattern, ruminal inactivity, and resting behavior. As expected, the number of triphasic and biphasic reticular spike bursts, as well as eating and resting behaviors, were affected by the type of forage ingested (A vs. C) on day 14 (p < or = 0.05). Moreover, the mode of distribution of concentrates affected also the variables measured (p < or = 0.05). Although the length of particles in complete mixed ration (B) was the same than in silage and concentrates given separately (C), the effect of regimen B on many variables was similar to that of regimen A or intermediate between A and C. The effect of regimens B and C was similar only for the rumination pattern, even though the number of boluses regurgitated for rumination differed (p < or = 0.05). PMID- 8434067 TI - Divergent effect of dehydroepiandrosterone on energy intakes of Zucker rats. AB - Oral dehydroepiandrosterone (DHEA) causes weight loss in the obese Zucker rat. To study this process, we fed lean and obese female Zucker rats either control chow diets alone or diets containing 0.6% DHEA for 4 weeks. DHEA treatment led to a significant increase in the caloric intake of lean-treatment rats and a significant decrease in obese-treatment rats compared to their respective controls. These phenotype-specific divergent effects began acutely and were sustained. The energy intake changes with DHEA treatment were significant after correcting for body weight. Divergent effects of DHEA were also observed in body weight changes and in the food efficiency ratios of the animals; DHEA affected obese rats but not lean ones. The results of the present study suggest that the appetite component of DHEA's antiobesity effect in the Zucker fatty rat cannot be discounted. PMID- 8434068 TI - Effect of destruction of dentate granule cells on kindling induced by stimulation of the perforant path. AB - Bilateral destruction of dentate granule cells in both the dorsal and ventral hippocampal formation had no effect on the threshold for hippocampal afterdischarge before or after kindling. Neither did it affect the number of stimulations required to attain kindling. However, the duration of afterdischarge was significantly longer in colchicine-lesioned animals compared to those receiving artificial cerebrospinal fluid. This was true for the threshold for afterdischarge as well as at the first and last kindling trials. These results suggest that dentate granule cells may inhibit the duration of afterdischarge induced by perforant path stimulation or that other postlesion changes occur which result in a prolongation of hippocampal afterdischarge. PMID- 8434069 TI - Ameliorative effects of the centrally active cholinesterase inhibitor, NIK-247, on impairment of working memory in rats. AB - Using a three-panel runway task, the effects of NIK-247 on impairment of working memory produced by scopolamine, hippocampal lesions, and cerebral ischemia were investigated in rats; these effects were compared with those of the well-known cholinesterase inhibitors, tetrahydroaminoacridine (THA) and physostigmine. Intraperitoneal injection of scopolamine (0.56 mg/kg) significantly increased the number of errors (pushes made on the two incorrect panels of the three-panel gates located at four choice points). NIK-247 (3.2-18 mg/kg PO), THA (1-10 mg/kg PO), and physostigmine (0.1 and 0.32 mg/kg IP) dose-dependently reduced the increase in errors induced by scopolamine. NIK-247 (32 mg/kg) was also effective in reducing the increase in errors produced by lesions of the dorsal hippocampus. A 5-min period of cerebral ischemia markedly increased the number of errors. NIK 247 (3.2 and 10 mg/kg), given immediately after blood flow recirculation and again 20 min before the runway test carried out 24 h after ischemia, significantly reduced the increase in errors expected to occur after ischemia. Tetrahydroaminoacridine (3.2 mg/kg) and physostigmine (0.1 mg/kg) similarly reversed the increased errors in ischemic rats. These results suggest that NIK 247 alleviates the impairment of working memory produced by scopolamine, hippocampal lesions, and cerebral ischemia, possibly through activation of the central cholinergic system. PMID- 8434070 TI - Learned control of meal size in spontaneously obese and nonobese bonnet macaque monkeys. AB - Ten pairs of obese and nonobese monkeys, matched for age and sex, received one liquid test meal a day for 4 days. Testing was conducted during the middle of a 6 h period of food deprivation. At all other times the monkeys were freely fed on maintenance chow biscuits. The first test meal of grape and orange flavor drinks familiarized them with fluids containing an intermediate level of added carbohydrate (CHO) (27.5%); equal volumes of grape and orange flavors were presented. During testing, the positions of the two flavors were switched three times, thus forcing the monkey to make four choices during the meal. On days 2 and 3, four pairs of monkeys received low-energy liquid meals (10% CHO), and six pairs received high-energy meals (45% CHO); half of the pairs in each group had orange flavor, half grape. On day 2, meal volumes did not differ between the 10% and 45% CHO groups; rather, the size of the meal (regardless of CHO composition) correlated with mean daily chow intake. On day 3, the volume consumed of the 10% CHO solution increased and the volume of the 45% CHO solution decreased, generating a difference between groups that indicated one-trial learning of control of meal size. On day 4, each monkey was given a test meal of repeated choices between samples of grape and orange flavor, both containing the intermediate 27.5% CHO.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8434071 TI - Hypophagic rats with dorsomedial hypothalamic lesions produce lighter and smaller pups with a lower survival rate at weaning than offspring of sham-operated controls. AB - Weanling and mature rats with dorsomedial hypothalamic nucleus lesions (DMNL rats) show reduced ponderal and linear growth and hypophagia and hypodipsia in the presence of normal body composition and anabolic hormone levels. The present study was conducted to assess their reproductive/parenting capacity and some offspring parameters. Four groups were used: DMNL mothers and fathers, DMNL mothers and control (SCON) fathers, SCON mothers and DMNL fathers, and SCON mothers and SCON fathers. The constituent rats of each group were bred to yield between 14 and 22 litters. The smallest litter size, litter weight, mean pup weight, percent of live-born and percent of weaned pups and greatest percentage of still-born pups were recorded when both parents were DMNL rats. The latter parents also cannibalized the majority of litters. The above parameters improved when only one parent was a DMNL rat, but this was still significantly below the offspring of SCON x SCON parents. The DMN is not part of the classical hypophysiotropic area (HTA), but earlier findings indicate hyperprolactinemia in DMNL rats. Therefore, the lesion-induced hypophagia during gestation and the postpartum neuroendocrine profile of the DMNL mothers may be the cause of the observed litter deficiencies and poor survival. PMID- 8434072 TI - Loss and recovery of sodium-salt taste following bilateral chorda tympani nerve crush. AB - The ability of the gustatory system to recover following peripheral nerve injury was investigated in adult hamsters. A conditioned taste aversion paradigm was utilized to test sodium salt-taste function after bilateral crush of the chorda tympani nerve and after nerve regeneration. Bilateral chorda tympani crush abolished expression of a previously learned conditioned taste aversion to 0.1 M NaCl. At 10 to 16 weeks following surgery, the hamsters were reconditioned three times to 0.1 M NaCl. The hamsters were able to relearn the conditioned taste aversion and by 16 weeks, the crush and sham groups showed equally strong and specific aversions to 0.1 M NaCl. A second surgery to cut the regenerated chorda tympani nerves resulted, again, in the loss of expression of the conditioned taste aversion. Thus, regenerated chorda tympani nerves are capable of carrying the information needed to form a conditioned taste aversion specific for sodium salts in the adult hamster. PMID- 8434073 TI - Differential resource use, growth, and the ontogeny of social relationships in the green iguana. AB - Growth rates, resource use, and ontogeny of behavior patterns were examined in captive groups of juvenile green iguanas (Iguana iguana). Four groups were housed in large arenas where supplemental heat and perch sites were limited, whereas two control groups were housed in similar arenas without limited resources. Growth, frequency and types of displays, behavioral interactions, and the use of resources were monitored. By 35-70 days of age, male hatchlings in arenas with limited resources could be classified into two groups: rapid growing dominant individuals and slow growing subordinate individuals. Growth and dominance were not correlated with size of individuals at hatching. Digestive efficiency of males was related to dominance and access to limited resources, but all lizards exhibited a similar digestive efficiency when maintained at a constant ambient temperature. Dominant males used the resources, especially supplemental heat sources, twice as often as subordinate males. The dominant/subordinate relationships and accompanying skew in body size were not evident in the control groups, or in females of any group. At 105 days, control groups were introduced to conditions with limited resources, resulting in increased aggressive interactions and divergence in growth rates. Onset of adult behavioral patterns was related to body size, and the species-specific signature display was observed in dominant males up to several months before subordinate males. These results indicate that male green iguanas establish a dominance hierarchy immediately posthatching when resources are limited, and as a consequence, both physiological and behavioral maturation are delayed in subordinate individuals. PMID- 8434074 TI - Assessing olfactory performance in a New World primate, Saimiri sciureus. AB - Using a task designed to simulate olfactory-guided foraging behavior, this study demonstrates for the first time that olfactory performance can be reliably assessed in squirrel monkeys. Small flip-top vials were fixed in random order to the arms of a climbing frame and equipped with odorized strips signalling either that they contained a peanut food reward (S+) or that they did not (S-), and three adult female monkeys were allowed 1 min to harvest as many baited nuts from this tree as possible. Given five 1-min trials per day, animals took between 15 and 25 days to reach the criterion of 80% correct choices, could readily transfer to new S+ or S- stimuli, and could remember the task even after a 1-month break. The precision and consistency of the monkeys' performance in tests of discrimination ability and sensitivity demonstrate the suitability of this paradigm for assessing olfactory function, and a first test of human subjects using the same cups and odorants showed that it may also be used to directly compare olfactory performance in human and nonhuman primates. PMID- 8434075 TI - Effects of salt intake on blood pressure and heart rate responses to footshock stress in SHR, BHR, and WKY rats. AB - The SHR shows chronic elevations in blood pressure in response to stress or a high salt diet, at least in some studies. Stress and salt have also been combined in studies in the SHR. Tonic levels of blood pressure are not clearly elevated by superimposing acute stress on top of a chronic high salt diet. The BHR is a new model with lower resting blood pressure and marked sensitivity to environmental stressors such as stress and dietary salt intake. In the present study, SHR, BHR, or WKY were placed on a normal or high salt (8% in chow) diet. During the 8th week of the appropriate diet, blood pressure and heart rate were monitored during rest and footshock stress. Salt elevated the resting blood pressure in all three strains, but only marginally in the WKY. Stress did not further elevate the effect seen with salt, although it had a differential effect on heart rate in the three strains. In SHR, the salt group had a higher heart rate, although in BHR it was no different, and in WKY it was lower, than that seen in same-strain normal diet groups. The results are discussed in terms of the ability of the combination of stress and chronic high salt intake to alter baroreflex function in SHR, although only marginally affecting it in BHR. WKY, on the other hand, do not show evidence of altered baroreflex function when an acute stressor is superimposed on a high-salt diet. PMID- 8434076 TI - Blood pressure during sustained inhibitory breathing in the natural environment. AB - Previous studies reported that breathing frequency of laboratory dogs decreased preceding the onset of an avoidance task and that this decrease was accompanied by increases in blood pressure and decreases in heart rate. Low frequency/normal tidal volume breathing has also been observed in ambulatory humans, but the cardiovascular concomitants of this inhibitory breathing pattern remain to be determined. The present study recorded blood pressure and heart rate in humans during periods of inhibitory breathing in the natural environment. Systolic and mean pressure were higher during inhibitory breathing than at other times, but no differences in diastolic pressure or heart rate were observed. Inhibitory breathing was differentially associated with the workplace and with social situations. Thus, major components of a physiological pattern that predisposes laboratory animals to sodium-sensitive experimental hypertension have now been observed to covary in ambulatory humans. Whether inhibitory breathing in the natural environment is a correlate or a cause of elevated blood pressure remains to be determined. PMID- 8434077 TI - Age-related differences in the timing of stimulus and response processes during visual selective attention: performance and psychophysiological analyses. AB - In this study, age-related differences in the selection of visual information were investigated. Two groups of younger and older subjects performed focused- and divided-attention (i.e., visual search) tasks. In the focused-attention task, centrally presented target letters could be flanked by compatible or incompatible noise letters. In the visual-search task, targets could be cued or uncued, and target locations could be spatially compatible or incompatible with the responding hand. P3 latency, lateralized readiness potentials, the electromyogram, and reaction times were used to detect possible age-related differences in the timing of stimulus- and response-related processes during selective processing of information. In the focused-attention task, performance of older subjects showed greater interference by incompatible flankers than did that of younger subjects because of stronger response competition caused by partial activation of the incorrect response channel by the incompatible flankers. No evidence was found of specific age-related differences in the efficiency of visual search in a divided-attention task. Furthermore, in both tasks, younger subjects showed an earlier start of response execution (in the electromyogram) relative to the onset of response preparation (lateralized readiness potential) and a higher percentage of incorrect electromyographic activity than did older subjects. PMID- 8434078 TI - Blood pressure responses and incentive appraisals as a function of perceived ability and objective task demand. AB - This experiment examined the role perceptions of ability may play in determining the impact of task demand on cardiovascular responses indicative of active coping. Subjects first performed a scanning task and received feedback indicating that they had either low or high scanning ability. They then were presented with the opportunity to earn one of two incentives by attaining either an objectively low or objectively high standard of performance on a second scanning task. Immediately prior to and during the 1-min performance period, systolic and diastolic blood pressure responses were greater in the difficult standard condition than in the easy standard condition for those who received high-ability feedback but were somewhat diminished in the difficult standard condition as compared with the easy standard condition for those who received low-ability feedback. Whereas high-ability subjects tended to have less pronounced pressor responses than did low-ability subjects when the second task was objectively easy, they had more pronounced pressor responses than low-ability subjects when the second task was objectively difficult. Analysis of goal attractiveness ratings obtained just prior to task performance showed a general correspondence between subjects' anticipatory blood pressure responses and their appraisals of the incentives. Implications for several lines of investigation are discussed. PMID- 8434079 TI - Electrophysiological evidence for task effects on semantic priming in auditory word processing. AB - Event-related brain potentials (ERPs) associated with semantic relatedness were recorded in two auditory word recognition tasks. In the Memorize task, subjects listened to a list of words in anticipation of a subsequent recognition test. In the Count Nonwords task, subjects silently counted the number of nonwords occurring within a list of words. Within each list, target words were either semantically related or unrelated to the immediately preceding word. As in comparable visual tasks, the amplitude of a negative ERP component (N400) was significantly attenuated when targets were preceded by semantically related primes. This attenuation was greater in the Memorize than in the Count Nonwords task. These data are consistent with the view that the sensitivity of N400 amplitude to semantic relatedness is modulated by task variables that manipulate depth of processing. PMID- 8434080 TI - Monitoring retrieval from long-term memory by slow event-related brain potentials. AB - Slow event-related brain potentials of nine subjects were recorded in an experimentally controlled long-term memory retrieval task (the Fan paradigm) from electrode sites F3, Fz, F4, Cz, P3, Pz, and P4. In all retrieval conditions, a very pronounced DC-like negative potential appeared over the left frontal cortex. This negativity was switched on with the presentation of the probe stimuli and prevailed in some conditions throughout the total recording epoch of 14 s. Particular retrieval conditions became manifest in distinct slow wave effects. The amplitude of a bilaterally distributed frontal negative slow wave increased when a more diversified associative structure had to be searched. The amplitude of another negative slow wave, which peaked bilaterally over parietal areas, was affected by the type of concepts that had to be retrieved. The amplitude was larger with general concepts (category labels) and smaller with specific concepts (category exemplars). These results suggest that distinct strategies are invoked when subjects are required to draw conclusions about different contents stored permanently in an associative network. PMID- 8434081 TI - Respiratory sinus arrhythmia: autonomic origins, physiological mechanisms, and psychophysiological implications. AB - Respiratory sinus arrhythmia (RSA) is being used increasingly in psychophysiological studies as an index of vagal control of the heart and may be among the most selective noninvasive indices of parasympathetic control of cardiac functions. A comprehensive understanding of RSA, however, requires an appreciation of its multiple autonomic and physiological origins. We review the physiological bases of RSA and show that RSA arises from multiple tonic and phasic processes of both central and peripheral origin. These underlying mechanisms are at least partially differentiated, have distinct dynamics and consequences, and may be differentially sensitive to behavioral and cognitive events. These multiple mechanisms are relevant for psychophysiological studies of RSA, and a thorough understanding of RSA can only be achieved through an appreciation of the dynamics of its underlying origins. There is a distinction between the psychophysiological and neurophysiological domains, and conceptual and empirical bridges between these domains are needed. PMID- 8434082 TI - Temporal stability of task-induced cardiovascular, adrenergic, and psychological responses: the effects of race and hypertension. AB - This study examined the test-retest reliability of task-induced responses of blood pressure, heart rate, norepinephrine, epinephrine, anger, and anxiety in 98 black and white normotensive and hypertensive individuals. Subjects completed three laboratory tasks (standing, mental arithmetic, and cold pressor) on two occasions 10 days apart. For all subjects, all baseline and test-retest correlation coefficients were significant (rs = .23-.71; median = .58). Baseline adjusted (residual scores) reactivity test-retest correlation coefficients were consistently smaller (rs = .02-.55; median = .36). In contrast to the white hypertensives, white normotensives, and black normotensives, the black hypertensives showed no significant baseline-adjusted test-retest correlation coefficients (rs = -.21-.40; median = .12). Epinephrine responses revealed a significant session by race interaction; blacks had 20% higher mean values and whites had 10% lower mean values upon retesting. The data suggest that race and hypertension may interact to affect the temporal stability of task-induced responses to stressors. PMID- 8434083 TI - The effects of between-source discriminability on attended and unattended auditory ERPs. AB - Event-related potentials (ERPs) for tone pips from attended and unattended sources, which varied on discriminability, were compared with ERPs for the same stimuli recorded during performance of a visual task. This comparison revealed that Nd, the negative shift of attended relative to unattended ERPs, consisted of three components: a negativity in the attended ERP from 100 to 270 ms, a positivity in the unattended ERP from 170 ms to the end of the epoch, and a second negativity in the attended ERP from 270 to 700 ms. In general, the later onset of early Nd with more difficult between-source discriminations could be attributed to the later onset of the positivity in unattended ERPs. A number of hypotheses were advanced for the origin of the unattended positivity: the suppression of the later of two negative components in the 100-220-ms range, an enhanced P2 component, an endogenous positivity, or the resolution of a protracted negativity elicited by preceding attended stimuli. PMID- 8434084 TI - The dimensions of an epidemic of violence. PMID- 8434085 TI - Tobacco use prevention and cessation programs in the U.S. Navy. AB - A representative sample of 406 U.S. Navy commands, including all medical treatment facilities, was surveyed in 1990 about their activities and programs to prevent the use of tobacco and promote smoking cessation during the preceding year. The vast majority of Navy commands (86 percent) provided some type of tobacco cessation educational materials or programs. However, the most common activities typically were rated as only "somewhat useful" in helping to curb tobacco use. Almost one-half of all commands offered psychological or behavioral cessation programs. Survey respondents estimated that approximately one-third of those persons who attended such a program stopped their tobacco use and nearly one-half reduced their tobacco use as a result of the program. Over-the-counter smoking cessation aids were not widely available at Navy exchange stores, individual commands, or medical treatment facilities. Furthermore, only 61 percent of all commands reported that they had a written policy or instruction regarding tobacco use. Only about one-third of medical treatment facilities had a routine system for identifying tobacco users by glancing at their medical records. However, it was estimated that 80 percent of medical treatment facility physicians routinely asked their patients about their tobacco use. The authors discuss the need for a more active Navy approach in prevention and cessation efforts and a routine system for identifying tobacco users from their medical records. In addition, inequities in cessation efforts were found among command subgroups. PMID- 8434086 TI - Survey of leadership skills needed for state and territorial health officers, United States, 1988. AB - As part of efforts to develop training and career development experiences to enhance leadership skills among public health officials, the Public Health Foundation, Association of State and Territorial Health Officials, National Association of County Health Officials, United States Conference of Local Health Officers, and Public Health Practice Program Office, Centers for Disease Control and Prevention, conducted a training needs assessment survey in 1988. Fifty-five State and territorial health officers were asked about potential knowledge, skills, and abilities (KSAs) that a prospective or new health officer might require in performing his or her job. Thirty-eight health officers returned completed questionnaires, a 69 percent response rate. For each KSA, respondents assigned scores from 1 (low) to 5 (high) to three different variables: the KSA's importance to job, as an initial ability of a new health officer, and as a desired ability for someone in that job. Of 78 KSAs, those scoring in the top 25 percent for importance to job were identified, and individual composite scores were calculated using the formula: (importance to job) x (desired ability minus initial ability). The top 10 mean composite scores ranged from 7.55 to 10.40 and were in five competence areas: public image (working with the community) (3 KSAs); policy development and program planning (3 KSAs); interpersonal skills (2 KSAs); agency management (1 KSA); and legal issues (1 KSA). These skills are not commonly acquired in schools of medicine or public health. Public health agencies should develop programs to assure that persons with leadership potential are identified early and given guided experiences and mentors, as well as specific training and education. Additional studies of public health officers are needed to develop and strengthen leadership KSAs among new health officers. PMID- 8434087 TI - A study of clients returning for counseling after HIV testing: implications for improving rates of return. AB - Pretest and posttest counseling have become standard components of prevention oriented human immunodeficiency virus (HIV) antibody testing programs. However, not all persons who receive pretest counseling and testing return for posttest counseling. Records of 557,967 clients from January through December 1990, representing more than 40 percent of all publicly funded HIV counseling and testing, were analyzed to determine variables independently associated with returning for HIV posttest counseling. On average, 63 percent of clients returned for posttest counseling. The rate varied by self-reported risk behavior, sex, race or ethnicity, age, site of counseling and testing, reason for visit, and HIV serostatus. In multivariate logistic models, persons who were young, African American, and pretest counseled in sexually transmitted disease (STD) clinics or family planning clinics were least likely to return for posttest counseling. Those clients who consider themselves to be at risk for HIV infection may be more likely to act on that perception and to follow through with posttest counseling than those who do not perceive risk. Counselors should make special efforts during pretest counseling to encourage adolescents, members of racial or ethnic minorities, and persons seen in STD and family planning clinics to return for posttest counseling by helping them understand and accept their own personal risk of HIV infection. Counselors need to establish, with the client's participation, a specific plan for receiving test results and posttest counseling. PMID- 8434088 TI - Strategies of a successful campaign to promote the use of equestrian helmets. AB - Although the risk of serious head injury for horse riders is higher than for most other sports, few equestrians regularly wear protective headgear. This study indicates that riders are well informed about the need for helmets and that the main reason for nonuse is inadequate helmet design. In particular, riders perceive that existing helmets are uncomfortable, expensive, and inappropriate for some riding styles. Based on these findings, the authors developed strategies to increase usage and incorporated them into a successful program. These strategies included working with manufacturers to develop a low-cost, versatile helmet; efficiently distributing educational literature among the horse riding community; and encouraging individual clubs and equestrian organizations to mandate a helmet policy. PMID- 8434089 TI - Need for HIV education among public health personnel in Michigan. AB - Knowledge and attitudes related to human immunodeficiency virus (HIV) and the use of the universal precautions recommended by the Centers for Disease Control and Prevention were investigated among 807 State and 2,797 local public health personnel in Michigan in September 1989. Survey results indicated that the majority of respondents were well-informed regarding the major routes of HIV transmission, but many respondents hold misconceptions regarding nonviable routes of transmission and about policies on HIV counseling and testing. Respondents reporting occupational exposure to blood or semen reported inconsistent use of universal precautions. Most respondents believed in providing the same quality of care for those with HIV infection as for noninfected persons. However, 32.4 percent believed that they should have the right to refuse treatment, and 9.4 percent reported that they would not be willing to provide routine public health services to an HIV-infected client. The results of this research suggest that in Michigan, public health personnel are in need of HIV education that focuses on the correction of misconceptions about HIV transmission, counseling, and testing policies; the development of appropriate attitudes toward persons infected with HIV; and the appropriate use of universal precautions. Findings also suggest that inadequate protective equipment is an important barrier to the consistent use of universal precautions. PMID- 8434090 TI - Should mammography screening be promoted if quality assurance is lacking? PMID- 8434091 TI - Taking exception to chronic fatigue syndrome prevalence findings by Price, et al. PMID- 8434092 TI - Illinois picks "Dracula" to symbolize AIDS threat to young people. PMID- 8434093 TI - Case study of the integration of a local health department and a community health center. AB - As rural communities struggle to sustain health services locally, innovative alternatives to traditional programs are being developed. A significant adaptation is the rural health network or alliance that links local health departments and community health centers. The authors describe how a rural local health department and community health center, the core organizations in publicly sponsored primary care, came to share a building and administrative and service activities. Both the details of this alliance and its development are examined. The case history reveals that circumstance and State involvement were the catalysts for service integration, more so than the need for or the benefits of the arrangement. The closure of a county-owned hospital created a situation in which State officials were able to broker a cooperative agreement between the two agencies. This case study suggests two hypotheses: that need for integrated services alone may not be sufficient to catalyze the development of primary care alliances and that strong policy support may override any local and internal resistance to integration. PMID- 8434094 TI - Physical, addictive, and psychiatric disorders among homeless veterans and nonveterans. AB - A cross-sectional survey of 1,431 homeless adults was conducted during the winter of 1989-90 at three shelters in Santa Clara County, CA, with a 98 percent response rate. Of the 1,008 U.S.-born men, 423, or 42 percent, were veterans, including 173 combat-exposed veterans and 250 noncombat-exposed veterans. There were 585 nonveterans. Both combat and noncombat-exposed veterans were significantly more likely to report excessive alcohol consumption before their initial loss of shelter than were nonveterans. Combat-exposed veterans had the highest prevalences of psychiatric hospitalizations and physical injuries before homelessness, 1.5 to 2 times higher than nonveterans and noncombat-exposed veterans. The length of time between military discharge and initial loss of shelter was longer than a decade for 76 percent of combat-exposed veterans and 50 percent of noncombat-exposed veterans. The extended time from discharge to homelessness suggests that higher prevalences of alcohol consumption, psychiatric hospitalization, and physical injury among veterans, especially those exposed to combat, may not have arisen from military service. It is possible, however, that such disorders may be considerably delayed before becoming serious enough to impact one's family, work, and the availability of shelter. PMID- 8434095 TI - The costs of a pediatric hospice program. AB - The recent literature on economic issues of hospice care leaves several questions unanswered. The most important issue concerns how this type of care can be made financially attractive to patients and families for whom it is a medical option. A major study of a home-based pediatric hospice program permitted a more careful analysis than was previously feasible of the charges for hospice care and how those charges are paid. Data on provider utilization and duration in the program were obtained retrospectively on 177 patients. Costs of incidental expenditures and indirect costs were obtained prospectively from the families of 27 patients. A cost model was developed which is general enough to be used by other hospitals that might contemplate establishing a similar hospice program. Our findings are that insurance coverage, especially for publicly funded patients, is likely to be a major impediment for families deciding whether or not to use a hospice program at home. PMID- 8434096 TI - States' responses to Title II of the Ryan White CARE Act. AB - Title II of the Ryan White Comprehensive AIDS Resources Emergency (CARE) Act of 1990 provides formula-based grants to States to help them improve the quality, availability, and organization of health care and support services for people with human immunodeficiency virus (HIV) infection. This article reviews State expenditures during the first year of CARE Act funding (April 1991-March 1992) within the context of Title II guidelines and the federally funded grant programs that preceded and helped shape Title II. The authors also discuss future challenges that require development of resources, the assessment of program impact, and the evaluation of the quality and appropriateness of HIV-related services. Ninety-one percent of the $77.5 million awarded to States during fiscal year 1991 went for the provision of medical and support services through HIV care consortia, drug reimbursement programs, home and community-based care programs, and health insurance initiatives. The remaining monies were used for planning, evaluation, and program administration. Forty States allocated $38.9 million for the establishment of HIV care consortia to assess service needs and to develop comprehensive continuums of health and support services in the areas most affected by HIV disease. Fifty States allocated an additional $28.3 million for the continuation or expansion of FDA-approved drug therapies for low-income people with HIV infection. Twenty-five States allocated $2.2 million for the provision of home- and community-based health services, and 16 States allocated $1.3 million for programs that help low-income people with HIV infection to purchase or maintain health insurance coverage. PMID- 8434097 TI - Project LEAN--lessons learned from a national social marketing campaign. AB - The Henry J. Kaiser Family Foundation initiated a social marketing campaign in 1987 to reduce the nation's risk for heart disease and some cancers. Consensus on recommendations for dietary change have stimulated the development of a variety of social marketing campaigns to promote behavior change. Project LEAN (Low-Fat Eating for America Now) is a national campaign whose goal is to reduce dietary fat consumption to 30 percent of total calories through public service advertising, publicity, and point-of-purchase programs in restaurants, supermarkets, and school and worksite cafeterias. The public service advertising reached 50 percent of the television viewing audience and the print publicity, more than 35 million readers. The toll-free hotline received more than 300,000 calls. Thirty-four organizations joined the foundation in partnership and raised $350,000 for collaborative activities. Thirteen States implemented local campaigns. Lessons have been learned about the use of the media, market segmentation, effective spokespersons, and successful partnerships. These lessons will be valuable to others planning social marketing campaigns on nutrition and other preventive behaviors. PMID- 8434098 TI - Food and Drug Administration surveillance of the role of foreign objects in foodborne injuries. AB - As part of its effort to assure a safe food supply, the Food and Drug Administration maintains a passive surveillance system for the reporting and followup of complaints related to food items. This surveillance system, called the Complaint Reporting System, records and investigates consumer complaints about the quality of a specific food item, its packaging, or unexpected effects following consumption of the food. This study, relying on data gathered from the 2,726 reports of discovery of a foreign object in a food item during fiscal year 1989, develops a profile of consumer complaints, focusing on those associated with resultant injury or illness. Fourteen percent of all reported cases of foreign object exposure cited resultant illness or injury. The most common foreign object reported in food is glass, and the most common injury is a laceration or abrasion of soft tissues of the perioral area, including the throat. There was a disproportionate representation of children younger than age 3 years with documented illness or injury. Only 3 percent of the complaints came from attending health professionals; 82 percent were self-reported. Practitioner awareness of the system is limited primarily because literature in this area is scant. The collection and investigation of reports of foreign objects in food are important because such reports provide early warnings of potential problems with manufacturers' food items. Although data suggest that severe injury from foreign object ingestion is rare, continued monitoring is warranted. Health professionals are encouraged to report such injuries through the existing system. PMID- 8434099 TI - Insurance coverage of special foods needed in the treatment of phenylketonuria. AB - Optimal medical management of phenylketonuria (PKU) requires the use of special low-phenylalanine foods for many years. For women with PKU, elevated maternal blood levels of phenylalanine even at conception can lead to fetal damage. Despite this need, private health insurance, Medicaid, and other public health programs often exclude the cost of these foods from their benefits. The New York State Department of Health conducted a survey of metabolic disorders treatment centers to elucidate the problems PKU patients have obtaining and paying for the special foods essential to their care. Payment for special foods was denied to nearly half of those with private health insurance policies and was covered for only 10 percent of Medicaid-eligibles. A public program for children with special health care needs covered these food costs in upstate New York but not in New York City. There is no program of assistance for adults who are not eligible for Medicaid and who do not have private insurance coverage of special foods. At present, many private health insurance policies and public programs do not cover the costs of low-phenylalanine foods other than infant formula. Payment for this essential part of the management of PKU should be mandated for all public programs for persons with chronic illnesses, public medical assistance (Medicaid) programs, and private health insurance. There is a need for a public program to assist adults with PKU who are not eligible for Medicaid and who do not have health insurance that covers these costs. PMID- 8434100 TI - Epidemiology of deaths from asthma in Pennsylvania, 1978-87. AB - Asthma affects an estimated 10 percent of the U.S. population and is the most common chronic disease among children. To determine one component of the public health burden of asthma in Pennsylvania, death certificates were reviewed of persons younger than 35 years who died from asthma during the period 1978-87. Blacks had nearly a sevenfold greater risk of death from asthma than whites. The highest death rates were found among black males and residents of the State's two largest urban areas, Philadelphia County and Allegheny County. A total of 67 percent of asthma deaths occurred outside of the health care system or in a hospital emergency department. Although reasons for excess deaths among black urban residents are not well understood, inadequate access to health care may play a role. Deaths from asthma are uncommon, but they are largely preventable. Intensified public health, preventive, and curative strategies regarding asthma need to be directed to the black urban population. PMID- 8434101 TI - Prevalence of artificial hip implants and use of health services by recipients. AB - Data from the 1988 Medical Device Implant Supplement to the National Health Interview Survey are used to summarize information about the prevalence of artificial hips among adults in the United States. The 1988 National Health Interview Survey was a cross-sectional survey of the civilian noninstitutionalized United States population, and included 122,310 persons in 47,485 households in a multistage probability sample. The supplement supplied the first population-based estimates of prevalence and morbidity of selected medical devices. Projected to the United States population, the survey results indicate that an estimated 674,000 adults were using 811,000 hip implants. Hip implant recipients were significantly more likely to be older, to be white, and to have lower educational, income, and activity levels than the general population of adults. After age-stratification, however, only differences in activity limitation and race remained. Current economic outlays for hip replacement surgery are substantial. With the aging population, use of health services by patients with artificial hips will probably increase unless measures to reduce the need for replacement surgery are instituted. These measures include reducing injuries and improving biomaterials. Further investigation is needed to examine the activity limitation and racial difference in prevalence found in this study. PMID- 8434102 TI - Factors associated with obtaining health screening among women of reproductive age. AB - Death and disability associated with breast and cervical cancer and hypertension can be reduced by early detection and treatment. The authors examined the rates for having obtained a Papanicolaou (Pap) test or pelvic examination, a breast physical examination, and a blood pressure test within the last 12 months among women of reproductive age in the United States in 1988, as reported by the 8,450 women interviewed for the 1988 National Survey of Family Growth. Overall, the annual rates of screening for women ages 15-44 years for those tests were 67 percent for a Pap test or pelvic examination, 67 percent for a breast examination, and 82 percent for a blood pressure test. Standard recommendations for the frequency of screening and survey data were examined to see whether actual screening practice was consistent with those recommendations. More than 90 percent of women who had a family planning service visit within 12 months received each of the tests, regardless of who provided the service or who paid for the visit. Women who were not sexually active, women with little education or low income, American Indian women, Hispanic women, and women of Asian or Pacific Islander descent had lower rates of screening than others, regardless of their risk status. These findings strongly suggest that the likelihood of having obtained screening among women 15-44 years old is determined primarily by how often a woman uses health care, rather than by her risk of disease. PMID- 8434103 TI - Attendance patterns of older adults in a health promotion program. AB - A group of 224 participants in a health promotion program for older adults had complete baseline data, including demographic information, self-perceived mental and physical health ratings, and measures of socialization and health limitations. Participants were offered exercise sessions 3 times a week, weekly health education classes, and a weekly stress management group. Their attendance at these classes varied from no classes to approximately 750 classes. Initially, participants were divided into the following 5 subgroups: 90 with virtually no attendance, and approximately 30 in each of 4 quartiles of class attendance. The group with the lowest attendance (first quartile) was found to be statistically like the group whose participants never attended any classes; these groups were combined. The Kruskal-Wallis One-Way Analysis of Variance was used to test for significant differences among the four groups on the variables of interest. In a comparison of the four groups from lowest to highest attendance, those participants with lowest attendance had lower incomes (P < .05), tended to live alone (P < .01), and were less likely to be able to climb two flights of stairs or walk a half-mile (P < .01) than those in greater attendance groups. Their socialization behaviors were poorer (P < .01), and their health often limited their activities (P < .05). PMID- 8434104 TI - Quality control of birth defect registry data: a case study. AB - The California Birth Defects Monitoring Program maintains a population-based registry of children born with congenital malformations. Trained data collectors routinely visit hospitals and genetics centers to identify cases and abstract information. These data are provided to the public health, medical, and lay communities and are used for conducting prevalence and case-control studies. A stratified sample of each data collector's work for one data year was reevaluated to assess the quality of case ascertainment and record abstraction. The sample included data from 109 facilities (37 percent) and 729 abstracts (5 percent). There are three steps in data collection: case-finding, the process of identifying potential cases; culling, the process of reviewing the charts of potential cases to determine which are reportable; and abstracting, the process of recording information from the charts of reportable cases. The probability that a potential case is missed during casefinding is 7 percent for small facilities, 4 percent for medium facilities, and 1 percent for large facilities. The probability that a reportable case is mistakenly classified as not reportable during culling is 3 percent for small and medium facilities and 1 percent for large facilities. The probabilities of incorrectly abstracting selected diagnoses and demographic items are slightly higher (8 percent for small and medium facilities and 6 percent for large facilities) because these are more complex processes than are casefinding and culling. Finally, the overall probability of missing a case from the registry is 3 percent. Therefore, these data indicate that the information collected by this registry are both reliable and complete. PMID- 8434106 TI - Survival at low dose in asynchronous and partially synchronized Chinese hamster V79-171 cells. AB - In an earlier study using cell sorting techniques to define the radiation survival response of asynchronous Chinese hamster V79-171 cells more accurately, we found evidence of substructure in the response at low dose. In the present work we have attempted to show that this substructure arises from the subpopulations of sensitive (G1, G2 phase) and resistant (late S phase) cells which are present in asynchronously dividing cultures but which are not resolved by conventional survival assays. Partially synchronized cells were produced by exposure to 1 mM hydroxyurea for 12 h and were harvested 15 min later, yielding a population of viable cells at or just beyond the G1/S-phase boundary. Parallel experiments were carried out with asynchronous cells. The average of repeated measurements of the radiation survival response of asynchronous cells again showed a significant difference (P = 0.002 to 0.009) between the alpha and beta values evaluated from the data for the low-dose range, 0-2.8 Gy, and the high dose range, 2.8-14 Gy. For G1/S-phase cells, however, there was no significant difference between the values of alpha and beta for the low-dose and high-dose ranges (P > 0.5). The results thus support the hypothesis that the observed substructure in the asynchronous response is due to resolution of subpopulations of different radiosensitivities, and they illustrate the advantage of the cell sorter assay for accurate measurements of cell survival, particularly at low dose. PMID- 8434105 TI - Heterosexual and mother-to-child transmission of AIDS in the hemophilia community. AB - Growing awareness of the potential modes of transmission of the human immunodeficiency virus (HIV) has encouraged interest in the epidemiology of infection among sexual partners and children of HIV-infected persons. The authors reviewed data on two groups, the first being those with HIV infection acquired heterosexually from a person whose hemophilia, or other chronic bleeding disorder, was treated with blood products. The second group was children with HIV infection acquired from a mother (vertical transmission) who either had been treated for a chronic bleeding disorder or had been the heterosexual partner of a person being treated. Surveillance data were examined for cases of acquired immunodeficiency syndrome (AIDS) in the United States reported to the Centers for Disease Control and Prevention, diagnosed before January 1, 1992, and for whom the only identified risk factor was being either the heterosexual partner or the child of a parent with a chronic bleeding disorder. Of the cases examined, 107 were in persons who were heterosexual partners of persons with chronic bleeding disorders. Of the 107, 98 (92 percent) were women and 87 (81 percent) were white; all were 17 years of age or older. In addition to the 107, there were 14 children, 10 (71 percent) of whom were diagnosed with AIDS in the first year of life. The rate of increase in such cases has not been as great in recent years as that observed early in the primary epidemic of AIDS among persons with hemophilia and other chronic bleeding disorders. These data underscore the risk of HIV transmission among heterosexually active couples, if one partner is seropositive, and the risk of transmission to offspring. Estimates of the prevalence of HIV infection among heterosexual women partners of HIV-infected men with hemophilia are comparable to estimates for women who had heterosexual contact with spouses infected with HIV from transfusions with cellular products. However, better data for estimates of persons at risk are needed to obtain more accurate comparisons. PMID- 8434107 TI - Effect of very low doses of gamma radiation on motility of gill ciliated epithelia of Mytilus edulis. AB - An investigation of the effect of gamma radiation on the motility of mussel gill ciliated epithelia was conducted using dose rates of 0.9 and 2 mGy/h. There was a definite decrease in the beat frequency and a distortion of the metachronal wave by 20-30 min after irradiation with 0.9 Gy/h. With a total dose of 0.9 mGy, the beat frequency was decreased 2- to 2.5-fold. In the period after irradiation a restoration of the metachronal wave was observed, but the beat frequency was about 50% of the control level. Gamma irradiation completely stopped the beating of the cilia when given at a dose rate of 2 mGy/h. PMID- 8434108 TI - Radiolysis in aqueous solution of dinucleoside monophosphates by high-energy electrons and fission neutrons. AB - The radiation chemistry in aqueous solution of the dinucleoside monophosphate d [CpT] and its sequence isomer d-[TpC] in air or nitrogen was examined using different qualities and quantities of radiations. High-performance liquid chromatography and gas chromatography-mass spectrometry were used to analyze the high-energy electron (13.2 MeV) exposure products or fission-neutron exposure products of d-[CpT] and d-[TpC]. A comparison of product profiles obtained from irradiated d-[CpT] and d-[TpC] suggests that, at relatively low radiation doses (50-250 Gy), products are formed by N-glycosidic or phosphodiester bond-cleavage, while at higher doses (500-1000 Gy) additional products were detected as a consequence of ring-modification mechanisms. The plots of radiation dose-yield and corresponding calculated G values of the released undamaged bases and nucleosides from d-[CpT] and d-[TpC] suggest a base-sequence dependence and a quality- and quantity-dependent response to ionizing radiation. Although the product quantities formed from sequence isomers were slightly different, we found no qualitative differences in the product formed at the lowest doses examined. PMID- 8434109 TI - A mathematical model for cell cycle progression under continuous low-dose-rate irradiation. AB - A mathematical model of the progression of cells through the mitotic cycle under continuous low-dose-rate irradiation is described. The model considers explicitly two special cases: (a) when a fraction of cells disintegrate and disappear after mitosis and (b) when a fraction of cells which have reached mitosis do not progress further but do not disintegrate either. We have established a relationship between the parameters of the model and dose and/or the age of the cell at exposure. This formalism is applied to studies of the effects of dose rate on HeLa cells (Mitchell, Bedford, and Bailey, Radiat. Res. 79, 520-536, 1979; 80, 186-197, 1979). Detailed information on the fraction of cells of a certain biological age at a given chronological time is needed because of the variation in the radioresponse of the cells as a function of age. PMID- 8434110 TI - Radiobiological intercomparison of p(45)+Be and p(65)+Be neutron beams for lung tolerance in mice after single and fractionated irradiation. AB - The lung tolerance in mice after single and fractionated irradiations with p(45)+Be and p(65)+Be neutrons produced at the isochronous cyclotron "CYCLONE" of Louvain-la-Neuve (Belgium) was studied. Cobalt-60 gamma rays were used for control irradiations. The end point was the dose which was lethal to 50% of the mice by 180 days (LD50/180). On a log-log plot, the slope (+/- SE) of the relationship between total isoeffect dose and fraction number decreases from 0.34 +/- 0.01 for gamma rays to 0.19 +/- 0.01 for p(65)+Be and 0.12 +/- 0.01 for p(45)+Be neutrons. The data have been analyzed using the linear-quadratic (LQ) model. The alpha/beta ratio (+95% confidence interval) increases from 5.3 (4.3 6.4) for gamma rays to 20.7 (16.7-24.9) for p(65)+Be and 37.9 (25.8-65.8) for p(45)+Be. The RBEs of neutrons relative to gamma rays were estimated from the LQ parameters, to 1.15 and 1.19 for a dose of 14 Gy gamma rays and 2.02 and 2.47 for a dose of 2 Gy gamma rays for p(65)+Be and p(45)+Be neutrons, respectively. The neutron RBE of the p(45)+Be relative to the p(65)+Be calculated from the ratio of their respective RBEs relative to gamma rays reaches 1.03 and 1.23 for doses of 14 and 2 Gy gamma-ray equivalent, respectively. These data are compared with other published data on lung tolerance after irradiation with lower-energy neutrons and with data obtained previously in our laboratory on mouse jejunum and Vicia faba. PMID- 8434111 TI - Subcellular distribution of various boron compounds and implications for their efficacy in boron neutron capture therapy by Monte Carlo simulations. AB - Neutron capture therapy has a promising role in cancer treatment since it can achieve selectivity at the cellular level. The effect of this therapy depends on the subcellular localization of boron atoms in the target cell. Five boron compounds were investigated in this study: the monomeric and dimeric sulfhydryl boranes (BSH and BSSB), a boronated phenylalanine (BPA), and two porphyrin complexes (BOPP and VCDP). The study shows that when exponentially growing rat 9L gliosarcoma cells are exposed to an isoeffective concentration of each of the five compounds for 1 h, BOPP produces a much higher intracellular level of boron than the other four compounds; BSSB produces the second highest level, while exposure to BSH, VCDP, and BPA resulted in lower intracellular boron levels. Subcellular fractionation studies showed that most of the boron localized in the cytoplasm of the cells with all five compounds. A significantly higher boron concentration was found in the lysosomes of the cells, but the nuclei contained only minimal concentrations of boron. Computer simulations of neutron capture reactions with boron using a Monte Carlo simulation code indicated that BOPP would yield the highest potential effectiveness, followed by BSSB, BSH, VCDP, and BPA, in that order. PMID- 8434112 TI - The response of Chinese hamster V79 cells to low radiation doses: evidence of enhanced sensitivity of the whole cell population. AB - High-resolution measurements of the survival of asynchronous Chinese hamster V79 379A cells in vitro after single doses of X rays (0.01-10.0 Gy) and neutrons (0.02-3.0 Gy) were made using a computerized microscope for locating and identifying cells (Palcic and Jaggi, Int. J. Radiat. Biol. 50, 345-352, 1986). The X-ray response from 1 to 10 Gy showed a good fit to a linear-quadratic (LQ) dose-survival model, but with X-ray doses below 0.6 Gy, an increased X-ray effectiveness was observed, with cell survival below the prediction made from the data above 1 Gy using the LQ model. The effect per unit dose (-log(e)SF/dose) increased by a factor of approximately 2, from 0.19 Gy-1 at a dose of 1 Gy to 0.37 Gy-1 at a dose of 0.1 Gy. This phenomenon was not seen with neutrons, and cell survival decreased exponentially over the whole neutron dose range studied. Further data suggest that this phenomenon is unlikely to be due to a subpopulation of X-ray-sensitive cells determined either genetically or phenotypically by distribution of the population within the cell cycle. The existence of low-dose sensitivity also appeared to be independent of dose rate in the range 0.016-1.7 Gy min-1. A possible explanation of these results is that the phenomenon reflects "induced repair" or a stress response: low doses in vitro (or low doses per fraction in vivo) are more effective per gray than higher doses because only at the higher doses is there sufficient damage to trigger repair systems or other radioprotective mechanisms. PMID- 8434113 TI - Critical steps for induction of chromosomal aberrations in CHO cells heated in S phase. AB - The following four effects on DNA replication are observed in cells heated in S phase of the cell cycle: (1) inhibition of replicon initiation, (2) delay in DNA chain elongation into multicluster-sized molecules > 160S, (3) reduction in fork displacement rate, and (4) increase in single-stranded regions in replicating DNA. Since cells heated in S phase manifest chromosomal aberrations when they enter metaphase, whereas cells heated in G1 do not, we attempted to determine if the effects on DNA replication are critical for the induction of chromosomal aberrations by studying these same effects during DNA replication when synchronous CHO cells had been heated (10 min at 45.5 degrees C) in G1 phase. Following a heat-induced G1 block (12 h), we found previously that when the cells entered S phase, replicon initiation was functional and chain elongation into multicluster-sized molecules > 160S was delayed but completed during S phase. In the present study, we find that the fork displacement rate was near normal and that there was no increase in single-stranded DNA. Additionally, an increase in excess nuclear protein induced in the heated G1-phase cells returns to a normal level by about 12 h, just prior to when the cells enter S phase. Since the excess nuclear protein remains for many hours in heated S-phase cells, we hypothesize that the excess nuclear protein is responsible for the drastic reduction in the fork displacement rate and the associated increase in single-stranded DNA. Furthermore, we hypothesize that this persistent increase in single-stranded DNA during replication is a critical step for the induction of chromosomal aberrations in heated S-phase cells. Consistent with this hypothesis, we observed that aphidicolin (1-2 micrograms/ml) treatment of S-phase cells for 13-16 h, which results in a twofold increase in single-stranded DNA during the inhibition of DNA synthesis, also induces chromosomal aberrations. Possibly, endogenous endonucleolytic attack occurs opposite these sites of single-stranded DNA, thus creating double-strand breaks which either can remain unrepaired or are misrepaired to account for the chromatid breaks and exchanges, respectively, observed as cells complete their cell cycle and enter metaphase. PMID- 8434114 TI - Two methods for assaying DNA double-strand break repair in mammalian cells by asymmetric field inversion gel electrophoresis. AB - The rejoining of gamma-ray-induced DNA double-strand breaks (DSBs) in mammalian cells was measured after various doses of gamma rays by using a version of pulsed field gel electrophoresis to elute fragments of DNA from an agarose plug into the lane of an agarose gel. Two approaches for measuring the kinetics of DNA repair were compared. In the first method, cells are irradiated and incubated at 37 degrees C in monolayers, after which the cells are suspended in agarose and DNA is isolated and subjected to electrophoresis. In the second approach, cells are suspended in agarose first, then irradiated and incubated for repair, and the DNA is isolated for electrophoresis. In both methods the kinetics of repair appears to be biphasic, with an initial fast phase and a second slow phase. At equal doses the t1/2 for fast repair is two-fold less in cells incubated in monolayers than in cells suspended in agarose (11 min compared to 20-23 min) and threefold less after subtracting the slow repair component. In the agarose method the t1/2 values for fast repair increase with increasing radiation dose, while in the monolayer method they are constant. In both methods t1/2 values for slow repair are approximately constant with radiation dose. At a given radiation dose, the level of initial damage is two- to threefold higher as assessed by the agarose method than by the monolayer method in which DNA repair can occur during the preparation of samples. The detection of higher levels of initial damage by the agarose method permits DNA repair to be assayed at doses as low as 8 Gy and enables fast repair processes to be assayed more readily. However, in the monolayer approach, repair occurs under normal growth conditions and is not subjected to the effects of prior manipulations and/or the rates of nutrient diffusion. Thus this approach might be more representative of normal intracellular repair kinetics. PMID- 8434115 TI - The role of intracellular pH changes in heat sensitization by procaine. AB - Although it has been known for many years that procaine sensitizes cells markedly to hyperthermia, the mechanism by which this occurs is not yet understood. The recent finding in our laboratory that procaine caused an intracellular acidification following heating prompted further studies using carboxy-SNARF-1 to measure the intracellular pH of cells during heating. We found that procaine actually causes an intracellular alkalinization during heating and the intracellular pH is lowered immediately after the extracellular procaine is removed. These results suggest that procaine causes acid loading analogous to ammonium chloride (NH4Cl) loading. Sensitization could not be attributed entirely to this acid shock, since a comparable acid shock with NH4Cl loading following heating caused only a slight sensitization compared to procaine. Heated cells acidified with NH4Cl loading recovered rapidly from the low intracellular pH, whereas the cells acidified with procaine loading did not. Cell sorting demonstrated that the cells which were unable to recover from acidification by procaine had significantly lower survival than those that recovered. Thus, in addition to causing an intracellular acidification following heating, procaine alters cellular processes responsible for recovery from an acid shock. PMID- 8434116 TI - Prolonged cell cycle delay in radioresistant human cell lines transfected with activated ras oncogene and/or simian virus 40 T-antigen. AB - Normal human diploid cell strains were transfected with an activated Ha-ras oncogene (EJ ras) and/or SV40 T-antigen. Clones expressing SV40 T-antigen alone or in combination with ras protein p21 were significantly radioresistant (D0 = 1.68-2.73 Gy) compared with their parent cells or clones transfected with the neo gene only (D0 = 1.20-1.35 Gy). This radioresistant phenotype persisted in postcrisis, immortalized cell lines. Cell cycle perturbations after X irradiations were studied in four immortalized, radioresistant cell lines transfected with EJ-ras plus SV40 T or SV40 T alone as well as in two nontransfected parental cell strains. Exponentially growing cells were exposed to various doses of X radiation and the distributions within the cell cycle were determined by flow cytometry. The time of onset and duration of division delay were also measured by cell counting. All cells underwent a dose-dependent G2 arrest; the duration of this division delay was proportional to radiation dose. The radioresistant cell lines had a longer arrest in G2 phase of the cell cycle compared to that of the parental cell strains. These data suggest that a prolonged cell cycle delay may be one of the factors involved in the radioresistance acquired by transfection of human diploid cells with SV40 T antigen. PMID- 8434117 TI - Radioprotective effects of calcium antagonists used alone or with other types of radioprotectors. AB - Diltiazem, a benzothiazepine calcium channel blocker used widely in cardiovascular therapy, protected mice against death by ionizing radiation. Diltiazem was active in male and female C3H mice and could be administered subcutaneously or intraperitoneally. Protection was also seen in BALB/c, C57Bl/6, and NMRI mice. Moderate activity was afforded by oral administration of effective levels of diltiazem. Injection at 10 or 30 min before irradiation was similarly effective, but injection 2 h prior to the irradiation provided only marginal protection. The dihydropyridine calcium channel blockers nifedipine and nimodipine were also effective, but since these compounds were in an ethanol containing solvent their radioprotective activity had to be distinguished from that of the ethanol. Synergistic effects occurred by combining diltiazem with zinc aspartate, dimethyl sulfoxide, and nifedipine. Protection by calcium antagonists may be due to interference with the damaging cellular influx of calcium after membrane injury by radiation-induced free radicals or by their direct inactivation. Calcium antagonists could play a role as less toxic radioprotectors, providing modest dose reduction factors but without the prohibitive side effects of aminothiols such as WR-2721. PMID- 8434118 TI - Concentration-dependent protection against X-ray-induced chromosome aberrations in human lymphocytes by the aminothiol WR-1065. AB - WR-1065, the free-thiol form of WR-2721, has radioprotective effects in various biological systems. We measured the efficiency of WR-1065 in modifying the induction of chromosome aberrations by X rays in human lymphocytes. G0 lymphocytes were incubated for 30 min in medium containing 1-12 mM WR-1065, exposed to 0 or 3.1 Gy 220-kV X rays, washed, and cultured for evaluations of chromosome aberrations and micronuclei (MN). Neither proliferation kinetics nor baseline frequencies of aberrations or MN were affected in nonirradiated cultures incubated in WR-1065 for up to 45 min. Radiation-induced chromosome aberrations and MN varied inversely as a logarithmic function of thiol concentration. At extracellular concentrations of 8-12 mM, WR-1065 protected against > 85% of X-ray induced chromosome damage as measured by either cytogenetic end point. WR-1065 is more efficient in modulating X-ray-induced chromosome aberrations than dimethyl sulfoxide, which provides protection by scavenging OH radicals. Our data suggest that mechanisms in addition to OH radical scavenging are involved in radioprotection by WR-1065. PMID- 8434119 TI - Decreased deletion mutation in radioadapted human lymphoblasts. AB - Survival and HPRT- mutant frequency were measured in human lymphoblastoid cells preexposed or not to a low dose of 0.02 Gy gamma rays and then treated with a high dose of 4.0 Gy. When compared to the high dose alone, the low-dose preexposure induced a 70% reduction of the mutant frequency, whereas cell survival was not affected. To understand the mechanisms underlying this phenomenon, the molecular nature of an HPRT- mutant collection was established using Southern hybridization analysis. Among mutants induced by irradiation with the high dose alone, 78% (21/27) had detectable alterations of the HPRT gene. In contrast, only 42% (15/26) of mutants which were "adapted" by the low-dose exposure were of this type. Moreover, the fraction of mutants with only partial deletions of the HPRT gene was significantly reduced (52 and 19% for the 4.0 Gy and 0.02 Gy plus 4.0 Gy induced mutant sets, respectively). In other words, the mutational specificity differed, depending on whether or not the cells were adapted. We suggest that low-dose preexposure leads to a reduced susceptibility to the mutagenic effect of a high dose of gamma rays by inducing an error-free repair system. Our data indicate that this putative system acts preferentially on the class of premutagenic lesions which produce deletions. PMID- 8434120 TI - Structure and action of mammalian ribonuclease (angiogenin) inhibitor. PMID- 8434121 TI - Regulation of repair of alkylation damage in mammalian genomes. PMID- 8434122 TI - Cell delivery and mechanisms of action of antisense oligonucleotides. PMID- 8434123 TI - Enzyme organization in DNA precursor biosynthesis. PMID- 8434124 TI - Identification and characterization of novel substrates for protein tyrosine kinases. PMID- 8434125 TI - Bacterial adenylyl cyclases. PMID- 8434126 TI - Initiation of transcription by RNA polymerase II: a multi-step process. PMID- 8434127 TI - Effects of 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, an inhibitor of Cl( )-HCO3- exchanger, on stress-induced gastric lesions in rats. AB - The effect of 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), an inhibitor of Cl(-)-HCO3- exchanger, on stress-induced gastric lesions was studied in rats. The stress exposure to rats was performed by restraint plus water immersion (22 degrees C) for 6 h. Oral administration of DIDS produced a dose dependent reduction in the gastric lesion formation. The ED50 value for DIDS was 94.4 mg/kg (64.2 - 138.8 mg/kg; 95% confidence limits) and the maximum effect was observed at the dose of 300 mg/kg with an inhibition of 95%. A dose-dependent reduction in lesions was also observed after administration of omeprazole, an inhibitor of proton pump. The ED50 value for omeprazole was 3.1 mg/kg (1.8 - 5.4 mg/kg; 95% confidence limits) and the effect was maximum at 16 mg/kg with an inhibition of 92%. These results indicated that DIDS protected the gastric mucosa against stress-induced lesions. It is speculated that the antiulcerous activity of DIDS may give a clue for the development of a new class of therapeutic drugs for the prevention and healing of gastric ulcers. PMID- 8434128 TI - Effect of solvents on rat liver cytosolic acetyl CoA:arylamine N acetyltransferase activity in vitro. AB - The effect of several solvents on the in vitro activity of rat liver N acetyltransferase (NAT) isozymes was examined. Dimethylsulfoxide (DMSO), dimethylformamide, dimethyl-acetamide, ethanol, and methanol all reduced NAT II activity in concentrations ranging from 1.25 to 10%. DMSO caused a similar magnitude of reduction in NAT I and NAT II activity. The inhibitory activity of DMSO was characterized as competitive in nature. These results indicate that solvents frequently used to solubilize arylamines may have significant inhibitory activity towards NAT in vitro. PMID- 8434129 TI - Pharmacological modulation of the spasmogenic response to methylxanthines in guinea-pig trachea. AB - The spasmogenic activity of methylxanthines was evaluated in guinea-pig isolated trachea treated with indomethacin (2.8 microM) and cooled to 20 degrees C. The contraction elicited by caffeine or theophylline (10 mM) was reduced in the presence of ouabain (10 microM), amiloride (100 microM), staurosporine (1 microM), H-7 (50 microM), polymyxin B (500 microM), K(+)-free solution, low Na+ (25 mM) medium or Ca(2+)-free (EGTA 0.1 mM) solution but was unaltered in the presence of verapamil (10 microM) or vanadate (10-100 microM). These results suggest that tracheal spasm to methylxanthines predominantly involves Ca2+ release from intracellular stores with a minor component due to extracellular Ca2+ entry through verapamil-insensitive pathways. A Na+/Ca2+ exchange process and the activation of protein kinase C may be also involved. PMID- 8434130 TI - Antagonism of acetaminophen hepatotoxicity by phospholipase A2 inhibitors. AB - A 250 mg/kg subcutaneous injection of acetaminophen (APAP) given to fasted mice was hepatotoxic as indicated by elevated serum alanine aminotransferase activity and electron microscopic studies. When extramitochondrial Ca2+ levels were 200 nM or greater, the APAP caused loss of mitochondrial Ca2+ homeostasis in a two step process that represents a sequence of events. The first step occurs 0 to 3 hours after APAP administration and the second step occurs 6 to 12 hours after APAP administration. Loss of mitochondrial Ca2+ homeostasis 6 to 12 hours after APAP correlates chronologically with nuclear damage as indicated by loss of nuclear Ca2+ sequestration between 6 and 12 hours after APAP administration. Pretreatment of mice with the phospholipase A2 (PLA2) inhibitors chlorpromazine or diltiazem one hour prior to APAP administration inhibits loss of mitochondrial Ca2+ homeostasis, prevents nuclear damage, and inhibits APAP hepatotoxicity as indicated by serum alanine aminotransferase activity and electron microscopic studies. This protective effect of chlorpromazine and diltiazem does not interfer with initial actions of APAP that influence mitochondrial function, but interfers with the sequence of events initiated by APAP that leads to loss of mitochondrial Ca2+ homeostasis and hepatotoxicity. PMID- 8434131 TI - An alternate nonisotopic technique of PCR-mediated allele-specific oligonucleotide analysis for the detection of a point mutation. AB - We report a simple protocol for the allele analysis of a point mutation using polymerase chain reaction. Conditions have been determined to use probes prepared for the conventional allele-specific oligonucleotide hybridization method directly. After amplification of the genomic region containing the mutation site, the nested polymerase chain reaction was performed using an allele-specific oligonucleotide probe as one side of the primer. Specificity of the amplification was achieved by decreasing the primer concentration in a two segment thermal cycling pattern. This protocol does not require additional special primers and an allelic mutation can be determined non-isotopically. PMID- 8434132 TI - Strength and endurance in the therapeutic evaluation of prednisolone-treated MDX mice. AB - The dystrophin-deficient, X-linked dystrophic mouse (mdx) was used to evaluate the efficacy of prednisolone treatment. A test protocol was used to take advantage of the quantifiable weakness and disability as well as molecular genetic defect shared with the X-linked Duchenne muscular dystrophy (DMD). Whole body weakness and fatigue were determined by non-invasive force-transducer physiographic and variable-speed treadmill techniques, respectively. Other measurements included hind-limb muscle protein, calcium, and histomorphology. Subcutaneously-administered prednisolone elicited significant improvements in whole body strength throughout a two-month test period. Increases in strength were also accompanied by measurable increments in running endurance. In fact, prednisolone treatment appeared to protect mdx mice from the stressful effect of continuous running as determined by strength and muscle fiber diameter. Test results from this study support the limited therapeutic benefit observed previously in DMD patients treated with the glucocorticoid. PMID- 8434133 TI - The decreased immune responses in macular mouse, a model of Menkes' kinky hair disease. AB - The macular mutant mouse is a murine model of the Menkes' kinky hair disease, characterized by a copper deficiency in serum. The immune response of its hemizygote (ml/y) was examined, herein. Ml/y mice which were not treated with Cu were atrophy of lymphoid tissues on day 14. However, kidney, brain, heart and lung weights were higher in ml/y mice without Cu treatment than in normal (+/y) mice. When compared to cells from +/y mice, spleen cells from ml/y mice exhibited similar proliferation-curves stimulated by Con A or LPS. Lymph node cells from ml/y mice showed a significantly decreased mixed lymphocyte reaction (MLR) response when stimulated by spleen cells from Balb/c mice. Spleen cells from ml/y mice demonstrated similar stimulation against lymph node cells from Balb/c mice. Antibody production against sheep red blood cells (SRBC) in vivo, a T cell dependent response, was suppressed in ml/y mice. By contrast, the antibody production against dinitrophenyl-ficoll, a T cell independent response was similar in +/y and ml/y. The antibody production against SRBC in vitro was also suppressed in ml/y mice. However, when the T cell-enriched fraction of ml/y mouse spleen cells was replaced by the T cell-enriched fraction of +/y mouse spleen cells, the antibody production against SRBC was recovered. The percentage of Ly-5 positive cells (B cell) from ml/y mice was greater than those from +/y mice. The percentage of Thy-1.2-positive cells (T cell) was decreased, and the decrease was most prominent with the L3/T4-positive T cell (helper T cell) subset. PMID- 8434134 TI - Liver regeneration in trypsin-fed partially hepatectomized rats. AB - Young adult Sprague-Dawley rats were partially hepatectomized (two-thirds organ removal) and administered a basal diet supplemented with various animal- and plant-derived enzymes (trypsin, alpha-chymotrypsin, pepsin, lipase, alpha amylase, malt diastase, ficin and bromelain) over a post-operative period of up to 10 days. Porcine or bovine dialyzed and lyophilized crystalline trypsin products containing 2400-3200 NF u/mg in addition to enteric-coated tablets with trypsin to chymotrypsin in a ratio of 6:1, were tested at supplementary levels of up to 4980 u/g ration. With the weight of tissue regenerated or the liver increment as indicator, trypsin in excess of 1000-1200 u/g ration proved inhibitory. This effect did not extend to alpha-chymotrypsin (levels of up to 4000 u/g diet) and the remaining 6 enzyme products specified above, nor to the s.c. injection of trypsin daily at 12,860 u/rat for the 1st 7 days. The last route promoted little change in increment with soy bean trypsin inhibitor (8.0 mg/rat daily for days 1 to 9). When a portion of the group fed a trypsin supplement of 2000 u/g was injected with phenobarbital i.p. at 80 mg/kg daily on each of the last 3 days, the resulting liver increment rose to the control range. As with lysine and arginine, acids of pertinence in tryptic proteolysis, no significant change was elicited by feeding a diet supplemented with peptone from tryptic digestion of casein. The enzyme-containing diets fed to sham-operated rats over a similar interval, did not affect the wet- or dry-liver weight per 100 g body weight. Microsomal parameters as total protein, cytochrome P-450 and the enzymes, aminopyrine demethylase and benzo[a]pyrene hydroxylase of livers from the partially hepatectomized or sham-operated rats fed trypsin and the other enzyme diets, presented no significant changes in the respective levels. The possible action of dietary trypsin in conjunction with inhibitors and growth factors controlling liver regeneration is discussed. PMID- 8434135 TI - Effects of reducing dietary [(Na+ + K+) - (Cl- + SO4=)] on the rate of calcium mobilisation by dairy cows at parturition. AB - The effects of feeding diets with different milliequivalents (meq) of dietary [(Na+ + K+) - (Cl- + SO4=)] to dairy cows during the last seven weeks of pregnancy on their acid-base status and calcium mobilisation rate around parturition were studied. Ten monozygotic twin pairs of pregnant cows (five pairs of parity 1 or 2, and five pairs of parity 3 or more) were allocated to two diets which were formulated to provide either -4 meq (anion diet) or +572.5 meq (cation diet) of [(Na+ + K+) - (Cl- + SO4=)] kg-1 dietary dry matter (DM). The daily rations consisted of 4 kg grass hay and 7 kg concentrates. Changes in meq of dietary [(Na+ + K+) - (Cl- + SO4=)] were achieved by adding KCl, K2SO4 and (NH4)2SO4 (anion diet) or K2CO3 (cation diet) to basal concentrates. Plasma calcium concentration and blood acid-base parameters were not affected by dietary treatment. However, urinary calcium excretion was markedly higher and urinary pH and bicarbonate excretion significantly lower in cows fed the anion diet than in cows fed the cation diet. The responses to hypocalcaemia induced by an intravenous infusion of EDTA solution were similar in the cows fed either diet. PMID- 8434136 TI - Critical differences of clinical chemical parameters in blood from dogs. AB - The study concerned the critical difference which may help to judge whether the difference between two consecutive analytical results may be safely ascribed to natural variation or not. To calculate the critical difference of nine canine clinical chemical parameters, blood samples from 20 apparently clinically healthy dogs were collected once weekly for five consecutive weeks. For each of the nine clinical chemical parameters, the total variance of the analytical results was divided into the component of variance between dogs (S2Inter), the component of variance for weeks within dogs (S2Intra) and the component of variance for measurements (S2Anal) using nested analysis of variance. The critical difference was then calculated from S2Intra and S2Anal as 0.22 mu kat litre-1 for alanine aminotransferase, 0.20 mu kat litre-1 for aspartate aminotransferase, 0.34 mu kat litre-1 for alkaline phosphatase, 2.36 mmol litre-1 for urea, 35 mumol litre-1 for creatinine, 2.8 g litre-1 for albumin, 6.3 g litre-2 for serum proteinTotal, 1.49 mmol litre-1 for glucose and 0.84 mmol litre-1 for cholesterolTotal. These critical differences may be used as guidelines to evaluate the difference between two consecutive analytical results of the above parameters. However, the analytical results should not be assessed by the critical differences alone, but should also be compared to the corresponding reference intervals. PMID- 8434137 TI - Influences of extracellular matrix components on the growth and differentiation of ruminal epithelial cells in primary culture. AB - Primary cultures of ovine ruminal epithelial cells were made to study the influence of collagen types I and IV out of medium supplementation with various hormones and Na-n-butyrate on cell morphology and growth characteristics. Both collagen type I and type IV led to increased cell proliferation with the stimulatory effect being more pronounced in collagen IV. In cultures grown on collagen I, both non-stratified and stratified colonies were found, whereas cultures grown on collagen IV showed predominantly stratified growth. Cells in both stratified and non-stratified colonies were positive for cytokeratin antibody. In non-stratified colonies, positive staining with fibronectin antibodies (FN-15) was found in a network over and around the cells. It is suggested that the non-stratified ruminal epithelial cells are in some respects similar to a 'non-differentiating keratinocyte' strain, derived from newborn foreskin epidermis. Cells in stratified colonies bound Ulex europaeus (UEAI) lectin which has been shown to be specific for differentiated epithelial cells in ruminal mucosa. Supplementation of culture medium with glucagon and insulin increased the total cell-overgrown area of collagen I cultures, whereas this effect was absent in cultures grown on collagen IV. In both cultures grown on collagen I or IV, hydrocortisone led to an increase in total cell-overgrown area, whereas Na-n-butyrate inhibited proliferation. PMID- 8434138 TI - Caffeine contractures, twitch characteristics and the threshold for Ca(2+) induced Ca2+ release in skeletal muscle from horses with chronic intermittent rhabdomyolysis. AB - Muscle from horses with intermittent exercise associated rhabdomyolysis was examined to determine if calcium regulation was abnormal. In vitro studies on semimembranosus muscle fibre bundles showed the time to 50 per cent relaxation of caffeine-induced contractures was shorter and the electrically elicited twitch longer in horses with exercise associated rhabdomyolysis. Substitution of strontium for calcium eliminated the difference in caffeine contracture between the normal and rhabdomyolysis horses. The threshold of calcium-induced calcium release was lower than normal in terminal cisternae-containing fractions of muscle from horses with rhabdomyolysis. Thoroughbreds with rhabdomyolysis had a shorter time to peak twitch tension than standardbreds, and normal thoroughbreds had a shorter caffeine contracture than normal standardbreds. There was no difference in fibre typing between breeds or groups. Either no histological changes or low grade to moderate degenerative myopathy was seen in muscle from horses with rhabdomyolysis. These results suggest horses with intermittent exercise associated rhabdomyolysis have abnormal calcium regulation. PMID- 8434139 TI - Hereditary necrotising myelopathy in Kooiker dogs. AB - A retrospective clinicopathological study of a neurological disorder in 22 Kooiker dogs (Dutch decoy dog) was made. The disease was found to occur equally in both sexes and clinical signs began at three to 12 months old. Physical examination revealed a progressive paresis of the hindlimbs. Post mortem examination showed symmetrical areas of malacia in the ventral, lateral and dorsal white matter of the spinal cord. In one dog dorsal white matter was spared. Cervical segments C4 to C8 were involved in all subjects. Rostral and caudal to these areas, Wallerian degeneration was prominent. The disease has much in common with similar myelopathies in the Afghan hound and the rottweiler. Indications of heritability were the similarity in clinical and pathological findings, the age of onset of the disease, and the significantly higher inbreeding coefficient in the patients than in the breed population (P = 0.001). All patients were descended from one pair. Segregation analysis suggested inheritance involving a simple autosomal recessive trait. PMID- 8434140 TI - An R-like protein of Streptococcus uberis stimulates opsonising antibodies. AB - A pepsin-sensitive R-like antigen with a molecular mass of 65 kilodaltons was extracted from Streptococcus uberis strain ATCC 19436 by trypsinisation and purified by diethyl-aminoethanol anionic exchange chromatography. The antigen reacted with sera from infected cows and stimulated opsonic antibody in the guinea pig. The amino acid composition of the antigen was generally similar to that previously reported for the R antigen of group C streptococci. PMID- 8434141 TI - Plasma potassium measurement with a new reagent carrier (Reflotron): comparison with ion-selective electrode results. AB - Potassium concentrations were measured in the plasma of 336 animals with a new reagent carrier (Reflotron; Boehringer Mannheim) K+ and with an ion-specific electrode system: results were highly correlated (r = 0.991; y = 0.993 x + 0.02) and day-to-day coefficient of variation of the new reagent measurements was lower than 2.5 per cent. This system offers a good alternative to the ion-selective electrode system for plasma potassium measurement in veterinary practice. PMID- 8434142 TI - Effect of bone strength on the frequency of broken bones in hens. AB - Bird weight, breaking strength of humerus and tibiotarsus and the number of bones broken during culling were recorded for four breeds of end-of-lay hens housed in battery cages. The probability of a bone being broken increased with bird weight and decreased with increasing bone strength. Bone strength increased with bird weight within each breed but the increase in strength was not great enough to prevent the extra damage suffered by heavier birds. There were differences in tibiotarsal strength between the four breeds of bird but overall no breed was more likely to suffer from broken bones than another. The rate of increase of bone strength with weight was similar between breeds and between humerus and tibiotarsus. The results show that differences in bone strength due to the type of housing system in which birds are kept are great enough to affect the ease with which bones are broken during bird handling during removal from cages at the end of lay. PMID- 8434143 TI - Capsular hyaluronic acid in Pasteurella multocida type A and its counterpart in type D. AB - Hyaluronic acid was demonstrated in the capsule extract of 39/39 Pasteurella multocida type A strains by sodium chloride gradient chromatography followed by Alcian blue staining, and by a turbidometric method using acidified horse serum. Treatment with hyaluronidase from various sources eliminated these reactions. An Alcian blue staining substance of closely similar chromatographic properties occurred in capsule extracts of 14/16 type D strains but it resisted hyaluronidase and was thought to be an acidic polysaccharide differing from the hyaluronic acid of type A. Turbidometric values were lower than with type A strains, but were unaltered by hyaluronidase treatment. The type D substance could be precipitated from capsule extract by acriflavin. Both type A and D strains were mucoid and displayed large capsule zones in stained preparations. Photomicrographic measurements showed that hyaluronidase treatment of cell suspensions markedly reduced capsule dimensions of type A but not type D strains. When type A strains were cross streaked against a hyaluronidase + Staphylococcus aureus, their growth became non-mucoid at the intersection: mucoid type D strains were unaffected. Neither hyaluronic acid nor the hyaluronidase resistant type D substance could be detected in type B or E strains. PMID- 8434144 TI - Pathology associated with meningoencephalitis during bacterial kidney disease of salmonids. AB - The neural pathology associated with spontaneous cases of bacterial kidney disease (BKD), in five species of commercially reared salmonids, was investigated histopathologically and with immunofluorescence. Patterns of localisation of the causative organism of BKD within the central nervous system suggest that haematogenous spread to the meninges, particularly the tela choroidea posterior, the tela choroidea and vascularised capsule of the saccus dorsalis and epiphysis of the epithalamus, and the saccus vasculosus of the hypophysis, appears to be a frequent route by which the central nervous system becomes infected. Retrograde extension from the posterior uvea to the floor of the diencephalon along the epineurium and perineurium of the optic nerve also may be a mechanism of neural invasion. Extension appeared to occur from these sites into adjacent areas of the meninges, the neural parenchyma and ventricles. Demonstration of bacteria within salmonid ependymal cells, as well as the apparent ability of salmonid ependymal cells to respond metaplastically suggest a similarity to mammalian type III ependymal cells (tanycytes). Based on this study, it is apparent that teleosts can survive protracted severe brain damage. This, combined with the apparent similarities of neural response to infection between the salmonids used in this study and higher vertebrates, suggests that teleosts may be a useful lower vertebrate model for studying the pathogenesis and sequelae of bacterial meningitis. PMID- 8434145 TI - Effect of stage of oestrous cycle on tylosin disposition in genital tract secretions of cows. AB - The influence of physiological state (oestrous or luteal phase) on tylosin disposition in genital secretions was examined after intravenous administration of tylosin to cows. Six healthy, cyclic and non-lactating dairy cows with controlled oestrous cycles were given a single slow intravenous injection of tylosin, at a dose of 10 mg kg-1. Plasma and genital fluid were regularly sampled up to 48 hours after injection. Tylosin diffused from blood to the genital tract and accumulated in genital secretions whatever the stage of the oestrous cycle: the secretion to plasma ratio was 3.45 +/- 2.54 during oestrous and 4.75 +/- 3.24 during the luteal phase. The area under the concentration-time curve (AUC) and the mean residence time (MRT) were significantly higher in genital secretions than in plasma. The AUC and the MRT in genital secretions showed no significant differences during the oestrous cycle. The minimal inhibitory concentrations (MIC) of tylosin for 25 strains of Actinomyces pyogenes were between 0.032 (12 strains) and 0.063 micrograms ml-1 (13 strains). Simulations based on the mean values of pharmacokinetic parameters determined in genital secretions, gave tylosin concentrations higher than the MIC for at least 36 hours. It was concluded that after an intravenous administration of tylosin, effective concentrations were achieved in genital secretions of the cyclic cow whatever its hormonal status which supported its use for the treatment of genital tract infections. PMID- 8434146 TI - Determination of the IgG index for the detection of intrathecal immunoglobulin synthesis in dogs using an ELISA. AB - The IgG index is a calculated quotient using IgG and albumin contents of cerebrospinal fluid (CSF) and serum to detect intrathecal IgG synthesis, which is important in the diagnosis of inflammatory infectious diseases of the central nervous system (CNS). An ELISA to measure IgG and albumin contents in blood and CSF was developed to determine the IgG index. Twenty-three normal dogs and 98 dogs with various neurological diseases were examined. In most dogs with infectious inflammatory diseases, with the exception of the acute form of nervous canine distemper, there was an elevation of the IgG index. Tumours of the CNS had an IgG index within the normal range. An elevation was found in lymphoid tumours or meningiomas with secondary cellular infiltration. Degenerative diseases, spinal cord compression and ischaemic myelopathy due to fibrocartilagenous embolism had normal or only slightly elevated IgG indices. In seven cases with inflammatory lesions there was no obvious CSF pleocytosis but the IgG index was elevated. In 17 cases in which infectious inflammatory disease was suspected, based on elevated CSF cell counts, inflammation could be excluded after determination of the IgG index. The reproducibility of the technique was found to be good and, considering the limited amount of time, expense and effort required, the determination of the IgG index in dogs is a useful extension of the conventional CSF examination. PMID- 8434147 TI - Production and purification of a low molecular weight haemolysin produced by Actinobacillus pleuropneumoniae serotype 1. AB - An unstable haemolytic activity produced by a strain of serotype 1 of Actinobacillus pleuropneumoniae was isolated when 1 per cent bovine serum albumin (BSA) was added to RPMI 1640 medium. BSA acts as a carrier molecule and stabilises activity. This haemolysin (BSA-haemolysin) was precipitated with ammonium sulphate, dialysed and lyophilised. Of the species tested, bovine erythrocytes were the most susceptible to the BSA-haemolysin while mouse and rabbit erythrocytes were the least susceptible. The haemolytic activity was dependent on the incubation temperature, no activity being observed at or below 24 degrees C. The haemolytic activity was also partly stabilised by 100 micrograms ml-1 dithiothreitol (DTT). The DTT-haemolysin was purified to homogeneity by ultrafiltration and high pressure liquid chromatography on a Protein Pak DEAE-5PW column. The molecular weight was estimated at 16 kDa by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and at 23 kDa by molecular gel filtration from the elution position of the haemolytic activity. The DTT-haemolysin activity was completely destroyed by pronase treatment suggesting that this substance could be a polypeptide. The addition of BSA to DTT haemolysin increased its activity and stability to lyophilisation. The addition of 10 mM calcium chloride in the titration assay increased the activity of DTT haemolysin from 220 to 476 haemolytic units ml-1. The BSA-haemolysin activity was only slightly affected by the addition of calcium chloride. PMID- 8434148 TI - Analgesic effects of detomidine in thoroughbred horses with chronic tendon injury. AB - This study was undertaken to assess the analgesia provided by detomidine (20 micrograms kg-1 intravenously) in thoroughbred horses. Pain thresholds to a mechanical noxious stimulus were measured before and after a period of mild chronic pain in one foreleg. Detomidine was a good analgesic in control animals; their pain thresholds were significantly elevated for about 60 minutes. After injury, the injured leg had a significantly lower pain threshold and the intensity and duration of analgesia provided by detomidine were significantly reduced. The analgesia in the opposite (sound) leg was also reduced, indicating that there were both central and peripheral aspects to this increased sensitivity to painful stimuli. Detomidine deserves to be considered as a potent analgesic in the horse rather than a sedative with analgesic side effects. PMID- 8434149 TI - Antibodies against Actinobacillus pleuropneumoniae serotype 2 in mucosal secretions and sera of infected pigs as demonstrated by an enzyme-linked immunosorbent assay. AB - Mucosal and serum antibodies against Actinobacillus pleuropneumoniae serotype 2 were demonstrable in an ELISA which used whole bacterial cells as antigen. Following experimental infection of pigs with A pleuropneumoniae serotype 2, specific antibodies against the bacteria were demonstrated in saliva and fluid obtained by bronchoalveolar lavage. There was a good correlation between the IgA antibody titre in this fluid and serum. As a result of natural infection, IgA antibodies were also demonstrable in the saliva at an early stage of infection when no serum antibodies were detectable. Later in the infection, when antibodies were present in the serum, salivary IgA antibodies were undetectable. The data suggest that the mucosal IgA antibody response arises before the systemic response. Measuring mucosal antibodies in saliva or nasal or bronchoalveolar fluid might therefore open the possibility of identifying pigs infected with A pleuropneumoniae at an early stage of infection. PMID- 8434150 TI - Plasma lipoprotein lipids in five different breeds of dogs. AB - Plasma and lipoprotein cholesterol and triglycerides, and apolipoproteins AI and B, were determined in five common breeds of pet dogs, labrador, beagle, West Highland terrier, cairn terrier and dachshund, kept under carefully controlled conditions approximating as closely as possible to normal domestic living. Although the total levels of both cholesterol and triglycerides in plasma did not vary significantly between the breeds, there were significant interbreed differences in the lipoprotein fractions. Thus high density lipoproteins (HDL) which are the major carriers of cholesterol in all dogs, was higher in the smallest breed, the cairn, than in the largest, the labrador. In contrast, the low density lipoprotein (LDL) was lowest in the cairn and highest in the labrador. Variation in HDL cholesterol levels arose from both subfractions, HDL2 and HDL3. Thus metabolic studies involving canine lipids should include measurement of lipoprotein lipids and take account of interbreed variation. PMID- 8434151 TI - Chemotherapeutic trials with four drugs in crossbred calves experimentally infected with Theileria annulata. AB - Groups of calves were infected by the injection of ground-up-tick supernatant from ticks infected with ODE-Anand stock of Theileria annulata, the causative agent of tropical theileriosis. Treatment with long-acting oxytetracycline, at 20 mg kg-1, injected intramuscularly, had no effect against severe Theileria annulata infection when administered either as a single injection on the day of infection or as three injections given on days 8, 10 and 12 after infection. Halofuginone lactate, given orally at 1.2 mg kg-1 was effective but caused anorexia, diarrhoea and debility. Parvaquone at 20 mg kg-1 intramuscularly given on day 11 after infection, had a marked suppressive effect, while buparvaquone was highly effective. A single treatment with buparvaquone, either at 5 mg kg-1 or 2.5 mg kg-1 intramuscularly, rapidly eliminated schizonts and piroplasms of T annulata. At 5 mg kg-1 it resulted in rapid recovery of all the treated calves. PMID- 8434152 TI - Disposition of 4-methylimidazole in goats and heifers. AB - 4-Methylimidazole (MeI) is formed when hay is ammoniated and it has been suspected of being the compound causing the 'crazy cow' syndrome. The aim of the present study was to describe the disposition of MeI in goats and heifers. The mean residence time was about five hours and the volume of distribution 0.9 litre kg-1 bodyweight in both goats and heifers. Goats metabolised MeI to a much higher extent than heifers which excreted the major part as the unchanged compound. MeI and its metabolites were excreted mainly in urine, but also in milk and faeces. In spite of administration of a dose (20 mg kg-1 bodyweight) which is much higher than the one intoxicated animals may have received through contaminated fodder none of the typical signs of intoxication were observed and it is concluded that MeI may not alone be the cause of the 'crazy cow' syndrome. PMID- 8434153 TI - Hypercholesterolaemia in briards in the United Kingdom. AB - Elevated fasting plasma cholesterol concentrations were identified in clinically healthy briards. Biochemical investigations revealed no other major abnormalities. Plasma lipoprotein electrophoresis demonstrated a marked increase in the intensity of the alpha 2 band (compared with control dogs) which was reduced by dextran sulphate-magnesium chloride or sodium phosphotungstate magnesium chloride precipitation of apo B and apo E containing lipoproteins in the plasma. The study has identified a hyperlipidaemia in briards characterised by increased cholesterol but normal triglyceride concentrations. The absence of obvious metabolic changes associated with secondary hypercholesterolaemia, suggests the breed may have a primary abnormality in cholesterol metabolism. The increased density of the precipitable lipoprotein which migrates to the alpha 2 band suggests that the hypercholesterolaemia may be due to an abnormal accumulation of high density lipoprotein (HDL) possibly HDLc. The possibility that abnormality in lipid metabolism might play a role in the development of retinal pigment epithelial dystrophy in briards is currently being investigated. PMID- 8434154 TI - Comparative pharmacokinetics of aditoprim in milk-fed and conventionally fed calves of different ages. AB - Aditoprim body disposition was described after intravenous and oral administration of 5 or 10 mg kg-1 bodyweight to milk-fed and conventionally fed calves with bodyweights of 80 kg, 160 kg and 210 kg. After intravenous administration to conventionally fed calves, aditoprim total body clearance increased and elimination half-life decreased with age. Oral administration of aditoprim with feed was associated with a longer absorption half-life and consequently longer elimination half-life in the older calves, because the drug was deposited in a functionally mature rumen. The weak base aditoprim is slowly absorbed from the rumen according to the pH partition hypothesis and probable binding to dietary fibres and other macromolecules. The favourable pharmacokinetics of aditoprim indicate a potential use for this antimicrobial in bovine practice, pending further studies on residue depletion profile, safety and therapeutic efficacy. PMID- 8434155 TI - Protection in lambs immunised with Haemonchus contortus gut membrane proteins. AB - Substantial protection against Haemonchus contortus was induced in lambs by hyperimmunising them with an integral membrane extract of intestines dissected from adult worms. The procedure was effective in young growing animals but did not afford any cross protection against either Ostertagia circumcincta or Nematodirus battus. A serum transfer experiment suggested that the effector mechanism was serum antibody which bound to the brush border membrane of the parasites intestinal cells. Sheep which had acquired immunity to H contortus by previous exposure to a trickle infection did not recognise the gut membrane proteins, which suggested that these are normally hidden from the host. PMID- 8434156 TI - [Sleep apnea syndrome]. PMID- 8434157 TI - [Prognostic factors and outcome of pulmonary thromboembolism]. PMID- 8434158 TI - [Idiopathic interstitial pneumonia]. PMID- 8434159 TI - [Pathogenesis of interactable respiratory infection]. PMID- 8434160 TI - [The relation between the anaerobic threshold and exercise-induced myocardial ischemia in patients with ischemic heart disease]. AB - The aim of this study was to clarify whether the anaerobic threshold (AT) in patients with ischemic heart disease is determined by exercise-induced myocardial ischemia. A) The reproducibility of the VO2 at the AT (AT VO2) were studied. In 13 patients with exercise-induced myocardial ischemia, submaximal Treadmill exercise tests were performed twice using a cardiopulmonary monitoring system. The reproducibility of the AT VO2 was good (r = 0.92), and the mean +/- SD was 1.3 +/- 8.2%. B) The change of the AT VO2 after percutaneous transluminal coronary angioplasty (PTCA) was studied. In 30 patients who underwent successful PTCA, submaximal Treadmill exercise tests were performed before and after PTCA using a cardiopulmonary monitoring system. After PTCA both the exercise duration and the peak VO2 increased significantly (569.0 +/- 200.8 sec vs 681.9 +/- 206.9 sec, p < 0.001: 19.5 +/- 3. 4ml/min/kg vs 21.3 +/- 3.7ml/min/kg, p < 0.001). On the other hand, the AT VO2 did not increase (13.7 +/- 3.0 ml/min/kg vs 13.9 +/- 3.2ml/min/kg, NS). The significant increase of the AT VO2, more than 15.1%, was recognized only in 5 patients. Neither did the AT VO2 increase even in patients without hibernating myocardium. In conclusion, there are many cases in which AT is not determined by exercise-induced myocardial ischemia. PMID- 8434161 TI - [Retrospective analysis of 15 cases with severe pulmonary embolism]. AB - We evaluated retrospectively the clinical indicators for the treatment of 15 patients with severe pulmonary embolism. All patients had moderate or severe pulmonary hypertension with deteriorated oxygenation. Thrombolytic agents and catecholamines were administered and mechanical ventilation was performed so as to treat right heart failure and improve oxygenation. In 14 patients, the pulmonary artery pressure decreased gradually and PaO2 increased in response to these therapies. The 14 patients were discharged from ICU without any symptoms. One patient died of cerebral hemorrhage due to the side effects of tissue plasminogen activator. We conclude that the pulmonary artery pressure and PaO2 are useful indicators for the treatment of the early phase of severe pulmonary embolism. Moreover, timely use of cetecholamine is very important for the maintenance of pulmonary circulation and acceleration of thrombolysis. PMID- 8434162 TI - [Use of a rate responsive pacemaker in sick sinus syndrome]. AB - In this study of 10 patients with sick sinus syndrome, we examined the benefits of a single-chamber ventricular pacing system that utilizes a sensor to detect the QT interval and then adjusts the heart rate. Changes in exercise tolerance capacity and cardiac function were evaluated when the pacing mode was changed from rate-variable mode (VVIR) to fixed-rate mode (VVI). Anaerobic threshold (AT), peak VO2 and cardiac output were measured in VVIR, during short-term VVI(VVI-S), which occurred two hours after the pacing mode was changed, and during long-term VVI (VVI-L), which occurred one month after the pacing mode was changed. 8 of 10 cases (80%) had their own beats during exercise. The AT and peak VO2 during VVI-S were not different from those during VVIR. However, AT and peak VO2 during VVI-L were significantly lower than those during VVIR pacing. (Respectively, 11.7 +/- 2.4 vs. 16.4 +/- 3.3, p < 0.01; 21.5 +/- 5.9 vs. 24.6 +/- 6.2, p < 0.01). At AT and peak VO2, there were no differences in cardiac output between VVIR and VVI-S, or between VVIR and VVI-L(NS). Physiologic changes in heart rate and cardiac output after exercise during VVIR were greater than those during VVI pacing. The present study suggests the above-mentioned changes after exercise effect, oxygen consumption in the peripheral circulation, which might lower exercise tolerance capacity in the chronic phase. The rate-variable pacing mode might improve exercise tolerance capacity and may be of benefit for patients with sick sinus syndrome. PMID- 8434163 TI - [A case of Behcet's disease associated with aortic regurgitation]. AB - A 42-year-old woman was admitted to our hospital because of anterior chest discomfort on exercise. She had already been diagnosed as having a complete form of Behcet's disease. On auscultation, there was a grade 2/6 diastolic regurgitant murmur along the left sternal border. Echocardiogram and pulse doppler led to the diagnosis of aortic regurgitation and mitral fluttering in diastole. Left ventriculography disclosed an enlarged left ventricular chamber, but the ejection fraction was 60% within the normal range. Aortography confirmed the diagnosis of aortic regurgitation (III.) and dilatation of the ascending aorta. The coronary arteriogram was normal. An endomyocardial biopsy of the right ventricular wall revealed mild hypertrophy of the myocardial fibers and interstitial edema. In this report, we discussed a case of Behcet's disease with reference to 28 cases reported in the medical literature in Japan. PMID- 8434164 TI - [A case of coronary artery embolism associated with combined valvular heart disease]. AB - A 53-year-old-man afflicted with combined valvular heart disease and atrial fibrillation was admitted to our department complaining of chest pain. ST elevation on ECG (II, III, aVF) and elevated CPK value were recognized. He was diagnosed as having acute myocardial infarction, and percutaneous transluminal coronary recanalization was performed immediately. The coronary angiogram showed occlusions at the proximal left branch (#12). But these lesions could not be recanalized by 960000 IU urokinase administration. The cineangiogram after one month revealed perfect recanalization of these occlusions. Mitral stenosis with neovascularity to the left atrium and aortic regurgitation were recognized. We supposed this infarction caused by coronary embolism originated from left atrial thrombi. Acute myocardial infarction associated with mitral stenosis has been reported in fifteen cases previously in Japan, but only three cases revealed coronary occlusion in the acute phase with normal coronary artery in the chronic stage. However, there has been no report, except for this case, demonstrating occlusion in two coronary arteries at the same time. So, our case is the first report of the involvement of two coronary artery occlusions. PMID- 8434165 TI - [Two cases of Marfan syndrome complicated with aortic dissection during pregnancy]. AB - Two women with Marfan syndrome who developed aortic dissection during pregnancy are reported. Case 1: A 38-year-old woman had experienced severe back pain five years before (at the age of 33) when she was in the 38th week of gestation, followed by labour with no problem. Three years ago, she was examined in our hospital for enlarged thoracic aorta pointed out in a somatoscopy and was diagnosed as having Marfan syndrome and aortic dissection of DeBakey type IIIb. Because her aortic dissection has been growing larger recently, surgical repair is scheduled electively. Case 2: A 32-year-old woman, who had been diagnosed as having Marfan syndrome because of ectopia lentis at 10 years old, was referred to our department for a painful tumor with pulsation which had emerged at the right hand side of her neck in the 32nd week of gestation. Acute aortic dissection of DeBakey type I complicated with acute aortic regurgitation was diagnosed, and emergency operation (Cesarean section, reconstruction of ascending aorta and aortic arch, replacement of aortic valve and aorto-coronary bypass to right coronary artery) was performed. Post-operative course was uneventful and the patient and her baby were discharged safely. In general, aortic dissection during pregnancy of patients with Marfan syndrome is of poor prognosis. Full consent by the patient and her family is necessary to decide whether the pregnancy should go on, and close cooperation among participating departments is indispensable for the treatment for this condition. PMID- 8434166 TI - [A case of primary cardiac amyloidosis with amyloid A protein]. AB - A case of cardiac amyloidosis in a 46-year-old male is reported. He was admitted for dyspnea. Physical examination revealed third and forth heart sound and hepatomegaly. Radiographic heart-thoracic ratio was 53%. Electrocardiogram showed first degree A-V block, rS pattern in V1-V4 leads, and ambulatory electrocardiogram showed ventricular tachycardia. Echocardiogram revealed hypertrophy and highly refractile echoes of the left ventricular wall. Endomyocardial biopsy was performed and it demonstrated amyloid fibrils, which were characterized immunohistochemically as Amyloid A (AA) protein, which is generally a constituent in secondary amyloidosis. Urine protein electrophoresis showed lambda type Bence-Jones protein, but bone marrow biopsy was normal. There was no evidence of malignancy, chronic inflammatory disease, or collagen disease. This case was diagnosed as primary amyloidosis with AA protein. It is rare that, in spite of its being a case of primary amyloidosis, its constituent protein is AA protein. PMID- 8434167 TI - [A case of parenchymal pulmonary endometriosis with recurrent chest pain]. AB - A 36-year-old woman was admitted to Nagasaki Citizens Hospital because of severe pleuritic chest pain associated with small amounts of hemoptysis. This episode occurred with the onset of her menses 2 months after a surgical abortion. Chest X ray revealed a nodular shadow in the left middle lung field. ECG showed no abnormal findings. Pulmonary perfusion scintigram and arteriogram showed no evidence of pulmonary thromboembolism. Over the next 5 years she suffered 5 further episodes of chest pain without hemoptysis, in which every episode coincided with her menses and disappeared within several days after the end of the menses. Chest X-rays disclosed transient nodular shadows on 4 of 6 of the above mentioned episodes. In the earlier episodes one nodular shadow was noted in the left upper lobe S5 a. Later, it was accompanied by an additional nodular shadow in the S5b. Those shadows disappeared in accordance with the diminution of chest pain. From these findings the diagnosis of pulmonary endometriosis was confirmed. Consequently, the antigonadotropin danazol was administered for 6 months. After this, she had no recurrence of her symptoms. Catamenial hemoptysis is usually the most striking symptom of pulmonary endometriosis, which might be an important clue for its diagnosis. The case presented here was characterized by severe chest pain with paucity of hemoptysis. PMID- 8434168 TI - [Respiratory sensory mechanisms of the nose and larynx, and their reflexes]. PMID- 8434169 TI - [Laparoscopic surgery and "respiration and circulation"]. PMID- 8434170 TI - [Use of muscle relaxants in the intensive care unit and degeneration of the skeletal muscle]. PMID- 8434171 TI - [Mechanism of discrepancy between mean pulmonary capillary wedge pressure and left ventricular end-diastolic pressure]. AB - It is well known that discrepancies between mean pulmonary capillary wedge pressure (man-PCWP) and left ventricular end-diastolic pressure (LVEDP) exist in the pathological heart with sinus rhythm. We discussed the mechanism of these discrepancies in the aspect of increased LV end-diastolic stiffness. Fifty-two patients observed in this study included 23 with old myocardial infarction (OMI), 4 with hypertrophic cardiomyopathy and 9 with hypertensive heart disease (LVH group), 6 with dilated cardiomyopathy (DCM), and 10 normal subjects (N). All 52 patients had sinus rhythm. Those with significant mitral and aortic regurgitation were excluded. End-diastolic LV stiffness was evaluated by the ratio of increases in LV pressure and volume during atrial systole (delta P/delta V), as proved by cardiac catheterization and cine-angiography. Discrepancies between m-PCWP and LVEDP were 5.9 +/- 4.3 mmHg in OMI group, 4.5 +/- 4.6 mmHg in LVH group, 5.8 +/- 4.5 mmHg in DCM, and 1.6 +/- 1.8 mmHg in N group. These discrepancies correlated well with delta P/delta V (r = 0.74). More significant discrepancies were observed in patients with so-called pseudo-normalized left ventricular inflow velocities proved by pulsed Doppler echocardiography, and in patients with marked concentric LV hypertrophy with increased delta P/delta V. In clinical observation, symptoms of heart failure may be determined by m-PCWP rather than LVEDP. We concluded that discrepancies between m-PCWP and LVEDP were caused by the booster pump function of the left atrium against increased LV end-diastolic stiffness. By the use of apexcardiogram and echocardiogram including the pulsed Doppler method, it was possible to predict these discrepancies non-invasively. PMID- 8434172 TI - [The effects of pharmacological autonomic blockade on the conduction system in patients with and without sinus node dysfunction]. AB - Electrophysiological studies were performed in 26 patients with sick sinus syndrome (SSS) and 12 controls before and after pharmacologic autonomic blockade (PAB) with propranolol (0.15 mg/kg) and atropine (0.04 mg/kg). Sinus cycle length (SCL) shortened significantly after PAB in both groups. PA and HV intervals did not change after PAB. AH interval shortened and Wenckebach period increased after PAB in SSS group. Maximum corrected sinus node recovery time shortened in the control group but did not change in the SSS group after PAB. Calculated sinoatrial conduction time shortened after PAB in both groups. Refractory periods of the atrioventricular (AV) node and the ventricle shortened significantly, but those of the atrium did not change after PAB. Linear relations existed between the change of SCL and the change of AH interval and of the Wenckebach period. These results suggested that the autonomic nervous system had the same effects on the sinus and the AV nodes in patients with SSS, and that parasympathetic tone was predominant on the sinus node, the perinodal tissue and the AV node under resting conditions. PMID- 8434173 TI - [The influence of pulmonary "venous" compliance on the static pulmonary compliance: a study of patients with left-sided heart disease with normal respiratory function]. AB - In heart diseases, such as mitral stenosis and angina pectoris, the static pulmonary compliance has been reported to be decreased. By definition, the pulmonary "venous" system consists of the pulmonary veins and the left atrium. It plays an important role as the reservoir for the left ventricle. In this laboratory, the pulmonary "venous" compliance (Cp"v") has been evaluated as delta V/delta P of a short segment of the P"V" volume-pressure curve. To evaluate the influence of Cp"v" on the static pulmonary compliance and to speculate about the mechanisms of the reduction in static pulmonary compliance in left-sided heart disease, hemodynamic data and static pulmonary compliance (Cst) were measured in 27 patients with left-sided heart disease. Cst was measured with esophageal balloon technique in a sitting position. The static volume-pressure curve was fitted by a sigmoid model: V = Vm/(1 + e(A-P)/kappa), where kappa is a shape constant and an index of the lung stiffness. The pulmonary blood volume (PBV) was estimated with our own method, using radionuclide (RN) angiocardiography. The mean pulmonary artery wedge pressures (PAW) were measured using a floating catheter. Cp"v" was calculated as the delta V/delta P from the increment of pulmonary "venous" volume (delta V) and that of PAW (delta P) that occurred during passive elevation of the legs. Pulmonary arterial compliance (Cpa) was obtained from an analysis of the diastolic decline in pulmonary arterial pressure wave forms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8434174 TI - [Transthoracic Doppler color imaging of the blood flows in the left coronary septal branches]. AB - This study characterized blood flow signals derived from the left coronary septal branches by transthoracic Doppler color flow imaging. In the anterior ventricular septum, the signal was detected in 7 of 13 patients with aortic stenosis, 8 of 34 with hypertrophic cardiomyopathy, and 5 of 144 patients with other diseased states. The peak diastolic flow velocity assessed by a pulsed Doppler technique ranged 21-115 cm/s (mean 57). Systolic signal was depicted in 13 of the 20 with the diastolic signal, indicating retrograde flow direction in all of them. The peak negative systolic component ranged 11-80 cm/s (mean 40). Peak diastolic flow velocity of the left anterior descending artery was higher in patients with the septal branch flow signal than in those without the signal (53 +/- 24 vs 31 +/- 11 cm/s). Patients with the signal showed larger transvalvular pressure gradient in aortic stenosis, and greater septal thickness in hypertrophic cardiomyopathy than in those without the signal. In conclusion, transthoracic visualization of the septal branch flow signal by Doppler color flow mapping is attributable to increased coronary blood flow at rest which is probably due to excessive load and/or septal hypertrophy. Augmented systolic retrograde flow may play additional role in the diastolic high velocity flow in the septal perforator. PMID- 8434176 TI - [A successful VA bypass treatment in patient with severe pulmonary hypertension]. AB - Report of a case of a patient with pulmonary hypertension associated with pericardial effusion who was treated by VA bypass during life-threatening right ventricular failure. A 63-year-old man was admitted to our hospital complaining of chest pain and dyspnea. Echocardiography revealed the patient had severe pulmonary hypertension and pericardial effusion. Though there were deep Q waves in ECG, his coronary angiography revealed normal coronary arteries. Pulmonary scintigraphy showed no evidence of pulmonary thromboembolism. As he developed hypotension and anuria, emergency pericardial drainage was carried out without any beneficial effect. Because no effective drugs were found to control his systemic hypotension and pulmonary hypertension, he was treated by VA bypass to save his life. Although his systemic pressure rose to normal level following institution of VA bypass, his pulmonary pressure remained high constantly, around 60-70mmHg. The VA bypass was discontinued on the 6th day because of bleeding tendency. 3 months after VA bypass, though he had not been given any drugs to control pulmonary hypertension, his pulmonary arterial pressure dropped down to within normal range. Though the exact mechanism or etiology of pulmonary hypertension remained unclear, this may be a rare case treated by VA bypass successfully for life-threatening right ventricular failure caused by pulmonary hypertension. PMID- 8434175 TI - [A histiocytosis X without histological findings: a new entity of histiocytosis X]. AB - Histiocytosis X is a disorder of the reticuloendothelial system with manifestations usually present in the form of one of three entities, namely; Letterer-Siwe disease, Hand-Schuller-Christian disease and eosinophilic granuloma of the bone. A 32-year-old female was admitted to our hospital in July 1990 because of a bilateral diffuse granular abnormal shadow in the chest. She had a history of bilateral pneumothorax in July 1987. She had been suffering from diabetes insipidus since October 1987, and amenorrhea since January 1989. Miliary tuberculosis, fungus disease, pneumoconiosis, sarcoidosis and collagen disease of the lung were excluded by laboratory examinations, and by observation of the clinical course. Histiocytosis X often combines pneumothorax, diabetes insipidus, amenorrhea and an abnormal radiograph of the chest. We suspected this case was one of Histiocytosis X. But, in her lung biopsy, neither Langerhans cells nor Birbeck granules were found. Furthermore S100 protein immunoperoxidase stain was negative. Therefore, we posit the existence of a new and different subtype of Histiocytosis X without histological findings. PMID- 8434177 TI - [IgA nephropathy with acute exacerbation of idiopathic interstitial pneumonia: an autopsy case]. AB - A 73-year old man was admitted to the hospital because of dyspnea. His proteinuria was pointed out in 1981. He felt dyspnea after exertion and abnormal chest X-ray shadow was pointed out in 1984. He was admitted to our hospital for further examination for the first time in 1988. He was diagnosed as IgA nephropathy by renal biopsy, and idiopathic interstitial pneumonia (IIP) by transbronchial lung biopsy. Then steroid therapy was begun because of progression of renal dysfunction in November 1990. But thereafter dyspnea, hypoxia and fine diffuse reticulonodular shadow on chest X-ray film was exacerbated. And he died because of respiratory failure. In this case, progression of IgA nephropathy seemed associated with exacerbation of IIP. PMID- 8434178 TI - [Development of left atrial thrombus after excellent mitral valvuloplasty for chronic severe mitral regurgitation]. AB - We report two cases with chronic severe mitral regurgitation and atrial fibrillation in whom left atrial thrombus was detected by transesophageal echocardiography after excellent mitral valvuloplasty. The reason why thrombus developed after valvuloplasty is that preoperative severe mitral regurgitation made the left atrial blood less stagnant than it was after surgery. Thus, even when mitral valvuloplasty achieves excellent results in patients with severe chronic mitral regurgitation and atrial fibrillation, anticoagulation and left atrial appendage ligation should also be considered. PMID- 8434180 TI - [A case of left atrial plication for mitral valvular disease with giant left atrium]. AB - A case of plication of giant left atrium complicating mitral valvular disease is reported. The patient was a 44-year-old female with mitral stenosis and regurgitation, whose respiratory function was severely disturbed. Chest X-ray showed severe stenosis of the left main bronchus and widening of the tracheal bifurcation secondary to compression by the left atrium. Mitral valve replacement and left atrial plication was performed. Postoperative respiratory weaning was uneventful and respiratory function was improved. We concluded that plication is very beneficial in patients with giant left atrium who have signs of compression of the bronchus and lungs. PMID- 8434179 TI - [A case of stunned myocardium: dual SPECT findings similar to acute myocardial infarction (AMI)]. AB - Emergent cardiac catheterization was performed on a 70-year-old female patient who was admitted for further evaluation of acute myocardial infarction. Coronary angiography didn't reveal any significant stenotic lesion, but levogram showed extensively abnormal contractility around the center of the apex region. On the second hospital day, 99mTc-PYP/201TlCl dual SPECT gave findings similar to those found in acute myocardial infarction, but myocardium--released enzyme stayed within the normal range. Two weeks after, 201TlCl myocardial scintigraphy showed disappearance of the perfusion defect, and normal contractility was observed on the levogram of the chronic phase. Since this case was clinically denied to be myocardial infarction, it was considered a typical case of stunned myocardium which showed prolonged left ventricular abnormal contractility with transient myocardial ischemia. This is a case suggestive for estimations of myocardial reversibility in patients with myocardial perfusion and metabolic disorder in dual SPECT. PMID- 8434181 TI - Epidermal growth factor and the kidney. PMID- 8434182 TI - Lipoxygenase products as mediators in immune-mediated glomerular injury. AB - Figure 4 is a schematic summary of current evidence implicating products of the 15-LO pathway of arachidonic acid metabolism, principally 15-(S)-HETE and LXA4, as endogenous antagonists for the proinflammatory actions of LTs. In this article, we have presented evidence for the pathophysiological relevance of LTs in glomerular immune injury, and the emerging data on the multifaceted counter inflammatory actions of 15-LO products as they relate specifically to the renal glomerulus. Clearly, these concepts are of a broader nature and would be expected to pertain to inflammatory reactions in general, be they in the glomerulus, the renal interstitium, or in extrarenal sites. The extent to which these early observations can be exploited to design strategies for the control of self destructive inflammatory reactions in the kidney and elsewhere will be determined by future studies. PMID- 8434183 TI - The intrarenal renin-angiotensin system. AB - In this article, we have discussed the localization of components of the renal renin-angiotensin system, as well as the existing information on the regulation of this axis and the effects of Ang II on renal function. All the components of the renin-angiotensin system are present in both fetal and adult kidney. In the adult kidney, renin is principally localized to jg cells of the distal afferent arteriole, where release is stimulated by increases in intracellular cAMP and inhibited by increases in cytosolic calcium. Four distinct stimuli mediating renin release are (1) NaCl sensed at the macula densa, (2) the sympathetic nervous system, (3) humoral factors, with Ang II, vasopressin, endothelin, and adenosine inhibiting renin release, and (4) changes in intrarenal blood pressure. Alterations in renal renin gene expression have been reported in pathophysiological states, such as salt depletion, diabetes mellitus, ureteral obstruction, Bartter's syndrome, and with high protein feeding. The highest renal concentrations of mRNA for the renin substrate angiotensinogen are found in the PT, where the protein is localized to subapical granules. Both salt depletion and androgens upregulate renal angiotensinogen mRNA. Of interest, renal angiotensinogen mRNA levels are lower in SHR than in normotensive WKY rats. As with angiotensinogen, renal ACE is mainly localized to the PT, with highest concentration on the brush border. The mechanisms of regulation of both renal angiotensinogen and ACE require further study. Using recently developed specific nonpeptide Ang II receptor antagonists, it appears that adult renal Ang II receptors are principally of the AT1 class, whereas fetal kidney Ang II receptors are of the AT2 subtype. By binding to AT1 receptors, Ang II exerts constrictive effects on both afferent and efferent arterioles, with increased effect reported on efferent arterioles. Glomerular Ang II receptors are localized to mesangial cells, mediating contractile responses resulting in changes in glomerular surface area and Kf, and potentially regulating mesangial sieving and phagocytosis. These receptors are reduced with salt restriction or in experimental diabetes. The highest concentrations of tubular Ang II receptors are found in PT, on both brush border and basolateral membranes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8434184 TI - The possible role of endothelin in the process of progressive renal deterioration in experimental and human glomerulopathies. PMID- 8434185 TI - The renal adenosine system: structure, function, and regulation. PMID- 8434186 TI - Functional properties of atrial natriuretic factor receptors. PMID- 8434187 TI - Urodilatin: a paracrine renal natriuretic peptide. PMID- 8434188 TI - Neutral endopeptidase 24.11: a modulator of natriuretic peptides. PMID- 8434189 TI - Erythropoietin production by the kidney. PMID- 8434190 TI - Platelet-derived growth factor in renal development and disease. AB - In aggregate, the evidence reviewed here supports a very important role for PDGF expression and action at local glomerular and interstitial sites in human kidney development and disease. PDGF delivered by platelets, or produced by endogenous cells of the kidney is capable of stimulating responses including proliferation, matrix deposition, chemotaxis, and contraction in renal cells, particularly mesangial cells and interstitial fibroblasts. During kidney development, PDGF may mediate processes of cellular recruitment, extracellular matrix deposition, and proliferation with the constructive outcome of glomerulogenesis and vascularization. Proliferation and production of extracellular matrix components by these cells likely contribute to destructive proliferative and sclerotic responses attending proliferative and other glomerulopathies. As additional information accumulates, therapeutic targets within the PDGF system may provide opportunities to arrest destructive renal processes. PMID- 8434191 TI - Insulin-like growth factor I and the kidney. PMID- 8434192 TI - [Current perspectives in medical psychology]. PMID- 8434193 TI - [Cardiac neurosis: the heart has its reasons...]. PMID- 8434194 TI - [The unbearable AIDS]. PMID- 8434195 TI - [Psychiatric care team, AIDS and the others...]. PMID- 8434196 TI - ["From alarm to broken body". Chronicle of an HIV infection]. PMID- 8434197 TI - [From coronary insufficiency to heart transplantation: prognosis of the psychosomatic specialist]. PMID- 8434198 TI - [Cervico-brachialgias, a delicate differential diagnosis: apropos of a patient with recurrent loss of consciousness in herniated disk]. AB - A protrusion of a intervertebral disc can be the cause of a painful hand-shoulder syndrome. Such a situation can be difficult to interpret particularly if it is associated with repeated (recurrent?) loss of consciousness. The presented patient illustrates the complexity of this syndrome and emphasizes the importance of the history and clinical examination. One should not be reluctant to repeat these investigations, in particular the examination of reflexes. The value of nuclear magnetic resonance studies in the diagnostic approach is outlined. A cervical disc protrusion is part of the differential diagnosis of unconsciousness of undetermined cause. Its pathogenesis remains to be elucidated. In the presented patient the causal relation is unquestionable since symptoms subsided after surgery. It is an example over our limited knowledge about the pathophysiology of peripheral nervous-system diseases. PMID- 8434199 TI - [Euthanasia?]. AB - Actual problems connected with euthanasia or assistance for suicide are outlined. Arguments of opponents, who underline the importance of palliating treatment at the end of life, are compared with arguments of proponents of euthanasia. PMID- 8434200 TI - [Urinary specific gravity--comparative measurements using reagent strips and refractometer in 340 morning urine samples]. AB - The specific gravity of urine (SG) indicates the number and weight of solute particles in urine; its measurement is helpful in interpreting proteinuria detected by dipstick tests and in monitoring adequate hydration in patients with nephrolithiasis. Four methods for measuring SG or osmolality of urine are currently available (depression of the freezing-point, urometry, refractometry, cation exchange on a reagent strip). Using a recently developed reagent strip, we have measured SG in morning urines of 340 non-selected outpatients and compared the results with SG measurements by refractometry of the same urines. In 86.2% of all urines, a good positive correlation between SG measured by reagent strip and refractometry was noted (r = 0.913, p = 0.0001). In 13.8% of the urines, however, the SG measured by reagent strip deviated by more than +/- 5 from the value obtained by refractometry; in 90% of these urines, glucosuria (reagent strip values too low or too high), proteinuria (values too high), or bacteriuria/leukocyturia (values too low or too high) could be found. In alkaline urine (pH > 7.0), SG values obtained by reagent strip have to be corrected by +5. PMID- 8434201 TI - [Round shadows in the thoracic roentgen picture, nicotine abuse]. AB - A 69 year old male patient was seen at our outpatient clinic because of a paravertebral mass in the routine x-ray-film of the chest. The patient was in good health, showed no loss of weight and complained only of slight cough probably due to his smoking habits. In view of these findings a benign lung tumor was suspected. However, the computed tomography of the chest revealed an aneurysm of the descending aorta which was successfully operated. PMID- 8434202 TI - [A case from practice (261). Poisoning with digitoxin-like glycosides following eating of oleander leaves]. PMID- 8434203 TI - [Pathophysiology of cor pulmonale]. AB - Chronic cor pulmonale is defined as right-heart hypertrophy or right-ventricular dilatation and/or chronic right-heart failure, secondary to disorders of the respiratory system. Most cases of cor pulmonale are secondary to chronic obstructive pulmonary disease. Other etiologies include restrictive lung diseases (e.g. idiopathic pulmonary fibrosis) and multiple pulmonary emboli, with the important, although small group of patients with chronic major vessel thromboembolism. In some instances abnormal ventilatory drive, disorders of the thoracic cage or neuromuscular diseases will eventually lead to cor pulmonale. Pathogenetic mechanisms involve hypoxic pulmonary vasoconstriction, mechanical narrowing of vessels and obstruction of the pulmonary vascular bed, which are discussed in further detail. PMID- 8434204 TI - [Arthroscopic treatment of subacromial impingement syndrome: possibilities and limitations]. AB - Serious impingement syndromes of the shoulder unresponsive to conservative measures can be relieved by means of the approved open anterior acromioplasty. However, the rise of shoulder arthroscopy allowed the same procedure to be performed arthroscopically. Based on an accurate indication the outcome of arthroscopic subacromial decompression may be considered as equally successful as that obtained by the open procedure. The advantages of the arthroscopic approach are: a significantly less gross destruction of the deltoid and--as a result--a reduced rehabilitation period a smaller incision and the possibility of an arthroscopic inspection of the joint prior to decompression For the repair of complete tears of the rotator cuff the arthroscopic procedure will provide less satisfactory long-term results. For those cases the open reconstruction will remain the treatment of choice. PMID- 8434205 TI - [What is your diagnosis? Acquired lactose intolerance]. PMID- 8434206 TI - [Principles and practice of malaria chemoprophylaxis and of malaria emergency medication for travelers]. AB - Malaria chemoprophylaxis and stand-by medication, avoidance of being bitten by mosquitoes, and instruction on the mode of infection, symptoms of disease and appropriate steps if malaria is suspected, are all crucial for malaria prevention in travellers. Drugs used for chemoprophylaxis do not prevent infection but help to avoid multiplication of parasites and disease. If a traveller is on stand-by medication, he decides himself according to symptoms when to take it; nevertheless, he is advised to see a doctor afterwards. Length of stay in an endemic area, health status of the traveller, malaria transmission rate and drug resistance determine the strategy of malaria prevention to be chosen. Risk benefit analysis of a chemoprophylactic regimen compares the risk of severe side effects of the drug with that of a life-threatening malaria attack. Stand-by medication presents an alternative, if the former outweighs the latter. The Swiss Working Group on Medical Counselling for Travellers updates guidelines for malaria prophylaxis. Recommendations for individual countries are regularly published by the Swiss Health Authorities (BAG). If chemoprophylaxis fails or if a malaria attack is not fully covered by stand-by medication, diagnosis and treatment can cause problems. PMID- 8434207 TI - [Febrile status in a traveler returning from the tropics with right-sided upper abdominal pain]. AB - This is a case report of a patient who presented multiple liver abscesses with Entamoeba histolytica five weeks after returning from an one-month trip to Thailand. This makes clear that a febrile patient returning from the tropics may not only be suspected of malaria, but that we should think about other possible febrile diseases. Respecting the incubation period and other clinical symptoms and signs, we are in most of the cases able to reduce the differential diagnosis to only a few possible ones. Diagnosis, treatment and follow-up are discussed. It is important to know that ultrasonography offers much help in the follow-up but that it may last months or more than one year to normalize the sonographic feature. PMID- 8434208 TI - [HIV transmission from mother to child]. PMID- 8434209 TI - [Travelers' diarrhea 1992]. AB - Traveller's diarrhea is a common problem without consequences for a healthy patient. Correct information, especially about hygiene habits during the trip, is most important. The prescription of an anti-diarrheal medication is usually justified but should not be given without proper information about the possible dangers. A prophylactic antibiotherapy is very seldom necessary. Antibiotic self medication can be a pragmatic alternative. Patients at risk must be identified before the trip, and appropriate measures are essential. Once the patient is back home again diarrhea will subside spontaneously and both patient and physician should therefore know to be patient. PMID- 8434210 TI - [What is your diagnosis? Cutaneous larva migrans]. PMID- 8434211 TI - [Traffic deaths and traffic injuries: also an economic problem for society]. AB - Based on an epidemiological observation on traffic accidents in the Swiss canton of Ticino, 1985, the following statement is possible: In Switzerland, 900 people die every year as a result of traffic casualties. Many victims of these accidents will be disabled for life. Direct and indirect costs of traffic injuries reach 3 billion Swiss francs a year. Only a small amount (6%) is devoted to medical treatment. The biggest part is due as compensation for lost income, disability allocations and loss of productivity. Among the avoidable fatalities those caused by traffic accidents have a very undesirable effect, because they involve mainly the young. More efforts should be undertaken to lower the mortality on the road, because it changes the Swiss population pyramid in a significant manner. PMID- 8434212 TI - [Essential cryoglobulinemia]. AB - The diagnosis of cryoglobulinemia relies on an in vitro artefact, i.e. the precipitation of immunoglobulins induced by a drop in temperature. Cryoglobulinemia has been described in association with neoplasia, infectious and connective tissue diseases. They are classified into two major groups: monoclonal or mixed (more than one type of immunoglobulin). In many patients the mixed type has been described as essential because of the absence of an associated disease. Recent evidence suggests, though, that more than half and probably up to 90% of mixed 'essential' cryoglobulinemias are in fact associated with chronic liver disease due to hepatitis C virus infection. This observation would be in accordance with the clinical response of half of these patients to interferon alpha therapy; however, more prospective studies are required to confirm the possible beneficial effect of interferon alpha. PMID- 8434213 TI - [A case from practice (262). Type I systemic scleroderma or acroscleroderma with cutaneous, pulmonary and esophageal involvement. Sicca syndrome]. PMID- 8434214 TI - [Total cystectomy: urinary derivation or bladder replacement?]. PMID- 8434215 TI - [Medical society and Revue Medicale de la Suisse Romande]. PMID- 8434216 TI - [Colpohysteropexy in stress urinary incontinence]. PMID- 8434217 TI - [The disintegration of urinary calculi via endoscopy: the lithoclast]. PMID- 8434218 TI - [Peripheral thrombosis in the sequelae of a stroke]. PMID- 8434219 TI - [Asthma, allergy, current aspects. Report of the "3A" of 23 May 1992: genetics of asthma and atopy]. PMID- 8434220 TI - [Leiomyosarcoma of the ovary]. PMID- 8434221 TI - [Georges Dieulafoy's "subcutaneous aspirator" (1869)]. PMID- 8434222 TI - [Current aspects of oncology in Lausanne]. PMID- 8434223 TI - [What physicians ought to know about L-carnitine: basic considerations]. PMID- 8434224 TI - The Nobel Lectures in Immunology. The Nobel Prize for Physiology or Medicine, 1984. Derivation and diversification of monoclonal antibodies. PMID- 8434225 TI - Identification of a vimentin-like function associated molecule (FAM) on rat NK cells: evidence for receptor function. AB - Monoclonal antibody (MoAb) 5C6 specifically binds to fish, rat and human NK cells and inhibits cytotoxicity. The molecule recognized by this MoAb is a 50-53-kDa membrane protein on rat leukaemic NK (CRC) cells. In the present study, we have obtained a partial internal amino acid sequence from a purified 42-kDa fragment of the CRC-function associated molecule (FAM). Three tryptic peptide fragments were sequenced and each showed homology to intermediate filament vimentin sequences as deduced from (GenBank) mouse cDNA sequences. Amino acid composition analysis indicated that similar to cytoskeletal vimentin, the FAM contained a high percentage of non-polar amino acids. To further assess the similarities between this protein and vimentin, two commercially available anti-vimentin MoAbs and one anti-vimentin polyclonal antibody were tested for binding and inhibition of NK cytotoxicity. All anti-vimentin MoAbs inhibited killing by rat NWNA cells of appropriate targets. Anti-vimentin MoAb 13.2 bound to 41% of NWNA cells compared with approximately 58% binding for MoAb 5C6. Capping and sequential binding experiments showed that MoAb 5C6 effectively removed, from CRC-cell membranes, the protein recognized by MoAb V9. Sequential addition of these two MoAbs (MoAb 13.2 followed by MoAb V9) to CRC cells did not produce competitive binding. Biochemical and Western blot analysis of the vimentin-like protein obtained from CRC cells indicated that this protein has a molecular weight of 48 50 kDa, with an isoelectric point of pH 6.1-6.3. This protein is cross-reactive by Western blot analysis with anti-vimentin and anti-intermediate filament (IFA) antigen MoAbs but not with anti-desmin or anti-actin MoAbs. The molecular weight heterogeneity (43 versus 48-50 kDa) of the CRC protein was also examined. Western blot analysis of the CRC extract after different in vitro incubation times at 37 degrees C and 4 degrees C demonstrated that the 50-53-kDa 'native' protein degraded to a 42-kDa protein by 24 and 48 h respectively. This degradation was inhibitable by 10 mM EGTA. Evidence is presented which indicates that a vimentin like protein on transformed rat NK cells may be an antigen binding receptor which initiates target cell lysis. PMID- 8434226 TI - Quantitation of Gm allotypes. AB - A method for quantitation of Gm allotypes is described. Alternative Gm allotypes of the three IgG subclasses, IgG1, IgG2 and IgG3, were investigated for the six most common Caucasian Gm phenotypes. Quantitation of G1m(a), G1m(f) of IgG1, G2m(n) of IgG2 and G3m(b) of IgG3 was performed with specific monoclonal antisera and purified myeloma proteins of different Gm allotypes. Mean +/- SD are given as percentage of a normal serum pool and in g/l for the Gm allotypes G1m(a), G1m(f), G2m(n) and G3m(b). For homozygous individuals the G2m(",") values are equal to the IgG2 levels and the G3m(g,g) values equal to the IgG3 levels. For heterozygous individuals the value for G2m(") is calculated as IgG2 minus G2m(n) and for G3m(g) as IgG3 minus G3m(b). Homozygous individuals have about double the amounts of the Gm allotype compared with heterozygous individuals. The gene activity of heterozygous individuals is given by quotients, mean +/- SD for G1m(a)/G1m(f) of IgG1, G2m(n)/G2m(") of IgG2 and G3m(b)/G3m(g) of IgG3 in different Gm phenotypes. Heterozygous individuals on all three IgG subclass loci have at least six different qualities of IgG molecules compared with three for homozygous individuals. PMID- 8434227 TI - Serum IgG and IgG subclass contents in different Gm phenotypes. AB - Different serum IgG and IgG subclass levels were found among Gm phenotypes of a normal population. One hundred and fifty-seven Caucasian blood donors were investigated for the reciprocal Gm allotypes on IgG subclass loci namely: for IgG1, G1m(f) and G1m(a); for IgG2, G2m(n) and G2m("); and for IgG3, G3m(b) and G3m(g), and subgrouped in the seven most common Gm phenotypes. The frequencies of Gm phenotypes and haplotypes were given, including numbers of the previously little known G2m(n,") heterozygous individuals. Mean serum quantities +/- SD and range of IgG, IgG1, IgG2, IgG3 and IgG4 were given for different Gm phenotypes. The IgG content was significantly lower in the Gm(f,",b/f,",b) phenotype in which the IgG2 levels were also significantly lower, compared with values of the other phenotypes. IgG3 levels were significantly lower in the Gm(a,",g/a,",g) phenotype compared with other phenotypes. These data imply the importance of Gm(f,",b/f,",b) and Gm(a,",g/a,",g) phenotypes causing lower amounts of IgG antibodies. In evaluating IgG subclass deficiency, the range for the low responding Gm(f,",b/f,",b) and Gm(a,",g/a,",g) phenotypes should be considered. PMID- 8434228 TI - Immunobiological studies on experimental visceral leishmaniasis. III. Cytokine mediated regulation of parasite replication. AB - The role of T-cell-derived cytokines in the regulation of Leishmania donovani replication was studied in a murine model. It was observed that in H-2d mice at the early and later stages of the disease IFN-gamma-secreting T cells predominate, whereas in between the above stages IL-4-secreting T cells predominate. Possibly, IL-4 abrogates the protective ability of IFN-gamma and thereby exponential parasite growth is ensured at the active stage of the disease. By contrast, H-2b mice were possibly incapable of inducing IL-4 secreting T cells and therefore parasite replication remains under control at any point post infection. PMID- 8434229 TI - Impact of HIV-positive sera on the functional activity of polymorphonuclear neutrophils from healthy donors. AB - The impact of the sera from 64 HIV-1-infected patients on the functional activity of polymorphonuclear neutrophils (PMN) from 9 healthy donors was investigated. Augmentation of PMN oxygen radical production in the presence of sera from HIV infected patients (PMN chemiluminescence) was demonstrated. This enhancement was connected with intracellular generation of chemiluminescence (CL). A significant correlation between this enhancement and stages of HIV infection was not found. The presence of the sera from HIV-infected patients in the incubation media led to a decrease of PMN phagocytosis. It was found that contrary impact of the sera on PMN CL and phagocytosis was connected with different factors. The decrease of PMN phagocytosis correlated with the level of complement and was independent of other factors. At the same time the increase of PMN CL was not connected with the level of complement activity but correlated with the level of anti-HIV antibody and circulating immune complexes. The reasons for this phenomenon are unclear. It was suggested that one of the serum factors which caused increase of PMN CL is HIV or HIV compounds. PMID- 8434230 TI - Neutrophil cytotoxicity induced by immune complexes prepared with cationized antibodies. AB - Here we analyse the ability of soluble immune complexes (IC) prepared with cationized antibodies to induce cytotoxic responses mediated by neutrophils. While cationized IC induced high levels of cytotoxicity, control IC induced very low levels of response. Inhibition of cytotoxicity by catalase but not by three haemenzyme inhibitors suggests that oxygen-dependent but myeloperoxidase independent mechanisms are responsible for cytolysis. While the response induced by control IC was enhanced by cytochalasin B and was not modified by colchicine, that induced by cationized IC was markedly inhibited by cytochalasin B and significantly enhanced by colchicine. Cytotoxicity induced by cationized IC was completely abrogated by monoclonal antibodies to Fc gamma RII. Using control IC, a partial inhibition was observed employing either anti-Fc gamma RII or anti-Fc gamma RIII monoclonal antibodies. Treatment of neutrophils with chemotrypsin or pronase significantly enhanced cytotoxicity induced by cationized IC but not by control IC. We also found that non-specific absorptive mechanisms appear to play an important role in the binding of cationized IC, but not control IC, to the neutrophil surface. The significance of these results is discussed. PMID- 8434231 TI - Characterization of a tryptase mRNA expressed in the human basophil cell line KU812. AB - The expression of a tryptic serine protease was detected in the cell line KU812 by Northern blot analysis with an oligonucleotide probe directed against a conserved region present in all of the five presently cloned human mast cell tryptases. PCR primers designed for the amplification of a nearly full-length copy of tryptase mRNAs were used to study the identity of the KU812 tryptase. Ten clones were characterized and all were found to be identical to one of the tryptases previously cloned from a human skin cDNA library. This tryptase has been thought to originate from mast cells of the skin. Two possible explanations may account for the observed identity between the presumed mast cell tryptase and the KU812 tryptase. Firstly, it is possible that the KU812 tryptase is a basophil specific tryptase which has previously been cloned from a human skin cDNA library containing low levels of cDNA copies derived from basophils in the starting material. Secondly, the KU812 cell line, and possibly normal basophils, express a tryptase which is identical to one of the tryptases expressed in normal skin mast cells. We cannot at present rule out any of the two possibilities, but we favour the second explanation as being the most likely. PMID- 8434232 TI - Interleukin-4 bypass of the immunosuppressive effect mediated by interleukin-2 receptor antibodies. AB - Numerous studies have demonstrated that the generation of alloreactive effector cells depends on cytokines. Conversely, there is evidence that cytokine metabolism is altered at the clonal level in tolerant chimaeras. This has led to preclinical and clinical studies using antibodies that antagonize interleukin-2 (IL-2), with the hope of achieving immunosuppression and inducing tolerance. Monoclonal antibodies against the alpha-chain (p55) of the human IL-2 receptor are being applied to prevent transplant rejection and graft-versus-host disease in several clinical trials. The antibodies that have been applied clinically so far antagonize the binding of IL-2 to the IL-2 receptor alpha-chain which is part of the high affinity IL-2 receptor, but they do not deplete the receptor-bearing cells. Our study investigates the immunosuppressive effect of monoclonal antibodies against the alpha-chain (p55) and beta-chain (p75). In mixed lymphocyte cultures the p55 antibody causes a reduction in T-cell proliferation to about 50%. The generation of cytotoxic T cells is reduced more effectively (up to 80%). By additional blocking of the IL-2 receptor beta-chain we achieved an additional but still incomplete immunosuppressive effect. Moreover we show that IL-2 receptor-blocked alloreactive T cells escape suppression by using IL-4 as an alternative stimulating signal. To prevent T lymphocytes benefiting from this alternative and thwarting the immunosuppressive effect, cytotoxic IL-2 receptor antibodies that deplete the high affinity receptor-bearing cells are needed. PMID- 8434233 TI - Purification of amyloid-associated heparan sulphate proteoglycans and galactosaminoglycan free chains from human tissues. AB - Basement membrane-associated heparan sulphate proteoglycans have been demonstrated immunohistochemically in organs from patients afflicted with various types of amyloidosis. In a recent report, we were able to isolate and partly characterize a basement membrane-associated heparin sulphate proteoglycan from human hepatic amyloid. In the present study proteoglycans were extracted with guanidine from human amyloid-laden kidney, spleen and lymph nodes. All tissues extracted with guanidine contained both heparan sulphate proteoglycan (HSPG) and galactosaminoglycan (CS/DS) free chains. Tissue staining using a monoclonal antibody against basement membrane HSPG revealed the presence of HSPG in amyloid deposits in kidney and spleen. Furthermore, following SDS-PAGE of HSPG from kidney after deaminative cleavage of the HS chains, a 15-kDa and 80-kDa protein appeared, probably representing the core protein(s). In lymph node HSPG, three core proteins of 65, 30 and 25 kDa could be demonstrated on SDS-PAGE, the first reacting with the anti-basement membrane HSPG antibody when subjected to Western blotting subsequent to SDS-PAGE. By immunohistochemistry, we failed to demonstrate any staining of the renal and splenic tissue sections employing an antibody against the decorin core protein. PMID- 8434234 TI - Suppression of mitogen-induced lymphoproliferation by soluble IgG Fc receptors in retroplacental serum in normal human pregnancy. AB - A competitive ELISA was used to quantify soluble IgG Fc receptors (FcR) in retroplacental serum (RPS) and peripheral serum (PS) from 10 women after uncomplicated full-term deliveries. The RPS contained significantly higher amounts of soluble FcR than did PS from the same individuals. RPS suppressed phytohaemagglutinin-stimulated lymphoproliferation as compared with PS, and a positive correlation (r = 0.66) was found between the degree of suppression and the difference in soluble FcR level between RPS and PS. Absorption of sera with Sepharose 4B coupled with heat-aggregated IgG strongly reduced the immunosuppressive activity, whereas absorption with Sepharose coupled with IgG F(ab')2 fragments did not. When IgG-binding material was eluted from Sepharose beads and added to cell cultures, the immunosuppressive activity was restored. The data indicate that soluble FcR at physiological levels have immunosuppressive properties. FcR-mediated immunosuppression may be of importance for maintenance of local immunosuppression during pregnancy. PMID- 8434235 TI - Leukaemic T cells from patients with chronic lymphocytic leukaemia of T-cell origin respond to Staphylococcus aureus enterotoxin superantigens. AB - We investigated the in vitro responsiveness of peripheral blood lymphocytes from two patients with T-cell chronic lymphocytic leukaemia (T-CLL) to Staphylococcus aureus enterotoxin (SE) superantigens. T-cell receptor (TcR) alpha beta (V beta 7.1)-expressing CD4+ leukaemic T cells from patient HE (white blood cell count 480,000/microliters) proliferated in response to SEA and, only at 1000-fold higher concentrations, to SEB, SED, and SEE. CD4+CD8+ TcR alpha beta (V beta 12.1)-expressing leukaemic T cells from patient KO (white blood cell count 120,000/microliters) were activated by SEB but not by the other tested SEs. In both instances, the activation of leukaemic T cells by SE was dependent on the presence of HLA-DR+ cells. Southern blot analysis of TcR beta gene rearrangement confirmed that the proliferating cells were derived from the leukaemic T-cell clone and not from contaminating normal T cells. These data indicate that leukaemic T cells from patients with T-CLL exert a clonally variable responsiveness to SE superantigens. We conclude that recognition of specific antigen and subsequent signal transduction can be initiated via the TcR of leukaemic T-CLL cells. PMID- 8434236 TI - Interferon-gamma stimulation of messenger RNA for human secretory component (poly Ig receptor) depends on continuous intermediate protein synthesis. AB - Secretory component (SC or poly-Ig receptor) plays a key role in mucosal external body fluids. The aim of this study was to elucidate the molecular events underlying IFN-gamma-dependent up-regulation of SC. Using a human SC cDNA clone isolated by our laboratory, we found that IFN-gamma up-regulated SC mRNA levels in a time- and concentration-dependent manner. Moreover, in situ hybridization showed a striking increase of SC mRNA-positive HT-29 cells after IFN-gamma treatment. Inhibition with 5,6-dichloro-1-beta-ribofuranosyl-benzimidazole (DRB) indicated a half-life for IFN-gamma-induced SC mRNA of approximately 1 h. Cycloheximide (CHX) abolished the IFN-gamma-induced accumulation of SC mRNA in a reversible manner; the time-course suggested that de novo synthesis of protein factor(s) with a turnover time shorter than 6 h was required for accumulation of SC message. IFN-gamma-stimulated up-regulation of SC expression therefore appears to depend on molecular events similar to those taking place for the activation of several other genes in the Ig supergene family. PMID- 8434237 TI - The alternative binding site for protein A in the Fab fragment of immunoglobulins. AB - Twenty-six new human or murine monoclonal immunoglobulins (IgM, IgA, murine IgG1 or human IgG3) with a known V-region sequence were tested for alternative (non Fc) binding to Staphylococcal protein A. Seven of them did not bind at all. Four immunoglobulins (all mouse IgG1) were bound but easily eluted (at pH 6). They were probably bound via the Fc part. All eleven were classified as negative for alternative binding. Fifteen immunoglobulins were found to bind more firmly; they came off the protein A column at pH 4-3 (alternative binders). Amino acid sequences of immunoglobulins that have been typed in the present work or earlier (25 binders and 26 non-binders) were compared. The light chain, the C region of the heavy chain and the D and JH segments look irrelevant for alternative binding. The N-terminal portion (amino acids 1-94) of the H chain probably forms the ligand of protein A. A peptide making the ligand cannot be reliably localized within this stretch but binder proteins had a high homology in residues 6-29. All mouse immunoglobulins expressing VH genes of families J606 or S107 were alternative binders; those expressing other families were non-binders. PMID- 8434238 TI - Virological and immunological studies in patients with acute viral hepatitis. AB - One hundred and seven patients with acute viral hepatitis (AVH) were studied prospectively regarding the viral aetiological agent HAV, HBV and NANB (by exclusion) using radioimmunoassay. Acute HAV infection occurred in 43 patients, and acute HBV infection in 34 patients, while HDS occurred in two patients only. Acute, presumably NANB, infection occurred in 28 patients. Ten out of 28 sera of patients with AHBV infection were positive for smooth muscle antibody by immunofluorescence. Important findings include: (1) presence of delta superinfection in the absence of HBsAg; (2) HBsAg as the only marker in two patients with AHBV infection; (3) concurrent presence of HBsAg and anti-HBsAg in three patients with AHBV infection. PMID- 8434239 TI - Structure of the T-cell receptor in a Ti alpha beta, Ti gamma delta double positive T-cell line. AB - The multichain T-cell receptor is composed of at least six different polypeptide chains. The clonotypic Ti heterodimer (Ti alpha beta or Ti gamma delta) is non covalently associated with the CD3 chains (CD3 gamma delta epsilon zeta). The exact number of subunits constituting the T-cell receptor is still not known. It has been suggested that each T-cell receptor contains two Ti dimers. To gain insight into the structure of the T-cell receptor we constructed a Ti alpha beta, Ti gamma delta double positive T-cell line which contained four functional Ti chains (Ti alpha, beta, gamma, and delta). The data demonstrated an absence of Ti dimers containing mixtures of chains other than the typical Ti alpha beta and Ti gamma delta combinations. Furthermore, by co-modulation experiments we demonstrated that the Ti alpha beta and the Ti gamma delta dimers were not expressed in the same T-cell receptor. Our data indicate that the T-cell receptor does not contain two Ti dimers. PMID- 8434240 TI - Pain and pain problems among subjects with systemic lupus erythematosus in Iceland. AB - This population study includes the majority of all systemic lupus erythematosus (SLE) patients in Iceland (n = 65). The study lists various self-rated pain descriptions both from a 54-item pain questionnaire and from the somatisation section of the Diagnostic Interview Schedule (DIS). Results show SLE patients to have significantly more joint and chest pain than does another patient group; to use analgesics more frequently; to have been in hospital more often during the past 10 years and to believe they know the reason for their pain. Also listed are factors that patients have found to increase and decrease SLE pain. PMID- 8434241 TI - Grip force in patients with rheumatoid arthritis and fibromyalgia and in healthy subjects. A study with the Grippit instrument. AB - The reliability of the grip force instrument, Grippit was tested on 51 right handed women of which 18 were healthy, 19 had rheumatoid arthritis (RA) and 14 had fibromyalgia (FM). Normative data was obtained from 169 healthy subjects. Results indicate that the reliability of Grippit was high in healthy and rheumatoid arthritic women and satisfactory in women with fibromyalgia. All patients showed greatly reduced grip force (RA had on average 21% and FM 40% of the control values) when compared to healthy women. Healthy women had on average 54% of men's grip force. The ratio between average force over 10 seconds and peak force was 73% for RA women, 69% for FM women, 83% for healthy women and 85% for healthy men. PMID- 8434242 TI - Characterization and functional assessment of patients subjected to occipito cervical fusion for rheumatoid atlanto-axial dislocation. AB - 20 patients with rheumatoid arthritis and atlanto-axial dislocation subjected to occipito-cervical fusion were studied. The patients were evaluated by a rheumatologist before surgery and 6-12 months after the fusion procedure. Joint tenderness was assessed by Ritchie's Index while the functional capacity was evaluated using a health assessment questionnaire and according to the classification by Steinbrocker. Localization and character of the symptoms from the head-neck region were registered. The neck pain was measured on a visual analogue scale. Radiographs of hands and wrists were obtained before surgery and joint destruction was classified according to the Larsen Dale Index. Reduction of pain and neurological symptoms was observed in the majority. There was, however, little evidence of improved functional capacity. PMID- 8434243 TI - Severe low-back pain. I: Clinical assessment of two weeks conservative therapy. AB - A standard clinical examination was performed by two independent investigators, before and after two weeks of conservative therapy, on 33 patients with severe low-back pain. Kappa coefficients indicated a higher reproducibility of neurological tests than of e.g. muscular tenderness or scoliosis. All patients were diagnosed by CT-scan and a disc herniation was found in 20. The clinical diagnosis was more in agreement with the CT-diagnosis after than before treatment. By discriminant analyses six variables were found to classify the clinical diagnosis correctly in 32 of the 33 patients: sensory loss, ankle jerk, soreness of back extensors, lumbosacral soreness, radiating pain and back extension test. Similarly, the CT-diagnosis was classified in 25 of 33 patients by the variables: sensory loss and limping. PMID- 8434244 TI - Severe low-back pain. II: Changes in CT scans in the acute phase and after long term observation. AB - No significant changes were noted in the CT-scan before and after 14 days of conservative therapy for low-back pain. Twenty of 33 patients had a disc herniation diagnosed on CT, and of these 18 patients were re-scanned after two weeks. Twelve patients were subsequently treated surgically, and of the remaining 8 patients 6 were re-scanned after 18 months. At this time the disc herniation had diminished significantly and was located in a more median position. In the 8 conservatively treated patients, the pain score at follow-up was related to the original size of the herniation (r = 0.72, p < 0.05). PMID- 8434245 TI - A four-year follow-up study in fibromyalgia. Relationship to chronic fatigue syndrome. AB - The primary objectives of this study were to examine to what extent fibromyalgia patients later on developed presumpted causative somatic diseases and to examine symptoms and muscle strength some years after the diagnosis of fibromyalgia was established. A secondary objective was to describe the overlap between fibromyalgia and chronic fatigue syndrome. Only in two of 91 the muscle pain was found to be caused by another somatic disease during the median 4 year follow-up period. In one of the 83 attending subjects a somatic disease associated with muscle symptoms was established at the follow-up visit. 60 out of 83 reported increased pain, 8 reported improvement of pain. The 83 subjects showed no significant fall in muscle strength during the follow-up period. The majority reported severe fatigue but only one fifth fulfilled the proposed chronic fatigue syndrome criteria. PMID- 8434246 TI - Rifampicin in early rheumatoid arthritis. AB - Sixteen patients with definite or classical Rheumatoid Arthritis (RA) of less than twelve months duration were recruited into a randomised, open twelve month study comparing Rifampicin 600 mg daily (9 patients) with Hydroxychloroquine (HCQ) 400 mg daily (7 patients). Ten patients completed twelve months of treatment (4 Rifampicin, 6 HCQ). Five patients were withdrawn from the study due to lack of efficacy (1 HCQ, 4 on Rifampicin). One further patient on rifampicin was withdrawn due to development of abnormal liver function tests. Significant improvement (p < 0.03) was noted in the Stoke Index (SI) at six and twelve months in the HCQ group which was not seen in the rifampicin group. In both groups there was no significant improvement in the single variables (Ritchie index, morning stiffness, grip strength, synovitis score, ESR, CRP). The results fail to confirm that Rifampicin may be useful in the treatment of RA in early stages of disease. PMID- 8434247 TI - Pneumonia, myocarditis and reactive arthritis due to Chlamydia pneumoniae. AB - A 37 year old HLA B27 negative man developed erythema nodosum, pneumonia, myocarditis and oligoarthritis due to Chlamydia pneumoniae. He recovered completely over a four month period. This is the first clinical description of reactive arthritis caused by C. pneumoniae. PMID- 8434248 TI - Idiopathic juvenile osteoporosis. AB - Osteoporosis is the most common bone disease in adults, but rarely occurs in children. A seven year old boy with idiopathic juvenile osteoporosis is reported. X-ray investigation revealed moderate generalized osteoporosis with compression fractures and wedging of the thoracic and lumbar vertebral bodies. Clinical examination and biochemical investigations ruled out the known causes of osteoporosis in childhood. During the following four years he complained of back pain, but no new fractures appeared. Entering puberty he improved both clinically and radiologically without treatment. PMID- 8434249 TI - [Goiter surgery from Kocher to today]. AB - When thyroid surgery was founded and developed by Billroth, Kocher, Miculicz, Halsted and De Quervain, a variable approach was used with respect to the extent of dorsal mobilization, completeness of goiter resection and finesse of the operative technique. These aspects of goiter resection are still of interest today: nodules are now considered as a growth marker and must be completely excised, necessitating careful dorsal mobilization; Kocher's correct plane of dissection is now anatomically defined as lying anterior to the lamella which covers the vessel and nerve-containing plate of the neck. In a prospective study, this technical approach for complete goiter excision has proven to harbour a low operative morbidity, to eliminate autonomous function, and to prevent goiter recurrence. PMID- 8434250 TI - [Current aspects in ergometry]. AB - Exercise testing remains an important non-invasive diagnostic test modality in patients with coronary artery disease. In recent years considerable advances have been achieved in the test methodology and in interpretation. The following points are important for the test methodology: (1.) The optimal exercise time is 8-12 minutes. (2.) The stepwise increases in work load should be as small as possible (ideally, according to the ramp protocol). (3.) Whenever possible patients should be tested on a symptom-limited basis. Submaximal ergometry is only indicated in the 2-3 weeks after acute myocardial infarction. (4.) The value of the exercise test depends mainly on the double product achieved (maximal systolic blood pressure x maximal heart rate). The interpretation of the exercise test should consider the clinical and hemodynamic responses and ST-segment changes. ST segment depressions are the most important diagnostic parameter. The ECG localization (most frequently lateral wall) does not necessarily correspond to the anatomic localization. Exercise capacity and blood pressure response are important prognostic variables. PMID- 8434251 TI - [Complications of superficial thrombophlebitis]. AB - Phlebitis and varicophlebitis are regarded as harmless diseases easily treated by compression and local measures such as incisions and applications. However, recent experience has revealed that they are often complicated by growth of the superficial thrombus into the deep veins, by noncontiguous calf thrombosis, and by usually asymptomatic pulmonary embolism. We prospectively examined 25 consecutive patients using duplex scanning (21x) and/or ascending venography (15x). The phlebitic process involved a varicose greater saphenous vein or a branch thereof (19x), the lesser saphenous vein (3x) or a nonvaricose superficial vein (3x). In 11 cases (44%) we found direct extension to involve the deep vein system and/or noncontiguous isolated calf or popliteal vein thrombosis. The presence of risk factors for deep vein thrombosis and a painful calf muscle were good clinical indicators of such complications. Patients with complications were anticoagulated on an outpatient basis. The course was uneventful in most cases. Our study confirms the notion that superficial thrombophlebitis is often part of a more extended thromboembolic process. This implies diagnostic and therapeutic consequences, although the prognostic significance of such complications is not clear at the moment. PMID- 8434252 TI - [Often unrecognized: erythropoietic protoporphyria]. AB - Erythropoietic protoporphyria is an autosomal dominant hereditary disorder with irregular penetrance. Recently, the first molecular DNA defects have been published. Various courses the disease may take are illustrated by three cases. The main symptom is photosensitivity, usually beginning in early childhood. Development of gallstones at an early age is one possible complication. Terminal liver failure, a rare but fatal complication, is due to intrahepatic protoporphyrin deposition and is treatable by liver transplantation only. Possible treatment schemes for photosensitivity and for liver involvement are discussed. PMID- 8434253 TI - [Unusual intestinal manifestations of tuberculosis]. AB - In an 87-year-old Swiss female referred with complaints of bloody diarrhea and weight loss, colonoscopy revealed three ulcers in the rectum and colon. Cultures from the colonic ulcers were positive for Mycobacterium tuberculosis. There was no evidence of pulmonary infection. One week after adequate therapy was begun, a perforation occurred at the rectosigmoid junction. The sigmoid was resected and left-sided colostomy was performed. Seven days after surgery the patient died. Clinical features, diagnosis and morphological changes of intestinal tuberculosis are discussed. PMID- 8434254 TI - [Concerning: "Homeopathy and its relationship to the unconscious--of physicians" by Rolf A. Adler (Schweiz. med. Wschr. 1992; 122:215-216)]. PMID- 8434255 TI - [Concerning: "Homeopathy and its relationship to the unconscious--of physicians" by Rolf A. Adler (Schweiz. med. Wschr. 1992; 122: 215-216)]. PMID- 8434256 TI - Speciation of plutonium in potato and the gastrointestinal transfer of plutonium and americium from potato. AB - Complexation of Pu(IV) and Am(III) by naturally occurring agents such as citrate and phytate might enhance their uptake from the digestive tract. However, the extent to which they enhance the gastrointestinal uptake of actinides from foodstuffs is far from resolved, as this study shows. Investigations of the chemical forms of Pu(IV) and Am(III), by gel permeation chromatography, in simulated digests of potato tubers naturally radiolabelled with 239Pu(IV) and 241Am(III) have shown that neither citrate nor phytate appear to determine their chemical forms. Therefore, it is possible that these are not the complexing anions which determine the gastrointestinal transfer of these radioelements from potato meal. Isotachophoretic analyses of the juices pressed from tubers and solutions prepared by simulated digestion of potato tubers have demonstrated the presence of several low molecular weight anions. These anions might be complexing agents because they possess an isotachophoretic mobility similar to that of citrate; some of these anions remain unidentified. Whereas 239Pu and 241Am were used in the foregoing studies, 238Pu and 241Am were used to produce either in vitro or naturally radiolabelled potatoes for gastrointestinal transfer measurements using rats and hamsters. Gastrointestinal transfer values of 0.13 +/ 0.05% (mean +/- standard error of mean) and 0.16 +/- 0.06% were determined with rats for the uptake of 238Pu and 241Am, respectively, from naturally labelled potato meal. Higher gastrointestinal transfer values were obtained for hamsters: for 238Pu and 241Am the transfer values from naturally labelled meal were 0.25 +/ 0.08% and 0.33 +/- 0.07%, respectively. Similar values were observed for uptake from in vitro labelled potato meal. On the basis of the similarity of the values for the naturally labelled potato meal and for the 'spiked' potato meal it would appear that biological incorporation is not necessary for the binding of the actinides to the ligands which will determine gastrointestinal transfer. PMID- 8434257 TI - Introduction: red blood cell membrane proteins, their genes and mutations. PMID- 8434258 TI - Mutations involving the spectrin heterodimer contact site: clinical expression and alterations in specific function. PMID- 8434259 TI - Molecular and cellular biology of the erythrocyte anion exchanger (AE1). PMID- 8434260 TI - Structure, function, and molecular genetics of erythroid membrane skeletal protein 4.1 in normal and abnormal red blood cells. PMID- 8434261 TI - The junctional complex of the membrane skeleton. PMID- 8434262 TI - A new paradigm in health. PMID- 8434263 TI - Financing health care in rural China: preliminary report of a nationwide study. AB - One unforeseen consequence of the change from collective to household production in rural China has been that the financial basis of the rural health services has been eroded. The majority of peasants now pay for health care on a fee-for service basis. A major initiative aimed at the establishment of prepayment schemes for funding rural health services is underway. A nationwide survey which compared health utilization and expenditure under different financing mechanisms was carried out in 1988. This paper presents the preliminary findings of that study. There is evidence that hospital charges were a barrier to inpatient care for those not covered by an insurance scheme. The data were less clearcut with regard to access to outpatient care. There is a need for further study which focuses on poor households and those living in remote villages. The study found that drug charges are an important source of revenue for the rural health services. The impact of this on prescription practices is an area which requires additional research. The cost of rural health services was relatively low. It is feasible to finance them almost entirely out of local resources in the more developed regions. The situation in the poorer provinces is more complicated. In spite of the fact that average health expenditure was almost 5% of household income in 1988, there was evidence of lack of access. This suggests that it may be more difficult to develop prepayment schemes to cover the full range of rural health services in the less developed regions. PMID- 8434264 TI - Stress, anxiety and depression: women's accounts of their health problems. AB - In a study of a stratified random sample of 356 Canadian women, stress, anxiety and depression were among the most frequently reported health problems. The first part of this paper outlines the different social characteristics of those who reported stress, anxiety and depression. Women experienced mental health problems differently depending on their socio-economic status, ethnicity, family structure, the quality of family relationships and the nature of their participation in the labour market. It is argued that we need a more detailed analysis of these aspects of women's estate if we are to understand the social production of mental health and variations between women. Subsequent sections of the paper discuss women's own understanding of the sources of their mental health problems. While they spoke of the particularities of their own lives, these were often located in the context of broader social influences. They emphasized the social aetiology of mental health, noting the importance of gender roles and images of women. They described the heavy workload of women, issues of identity and their social legacies. In conclusion, it is noted that women appear to normalize the mental health problems they report. This may, in part, reflect the lack of social reinforcement and validation of their experiences. PMID- 8434265 TI - Malaria chemoprophylaxis compliance in pregnant women: a cost-effectiveness analysis of alternative interventions. AB - Compliance to malaria chemoprophylaxis among pregnant women in Malawi has historically been low. Three separate interventions, based upon an ethnographic study of malaria beliefs among pregnant women in Malawi, were introduced to increase compliance to the malaria chemoprophylaxis program provided by the Ministry of Health. Each intervention consisted of a health education message and an antimalarial drug. A cost-effectiveness analysis of the interventions was conducted to compare the interventions as alternative strategies to increase compliance among pregnant women. PMID- 8434266 TI - Problems in the measurement and international comparisons of socio-economic differences in mortality. AB - The opportunities for research of socio-economic differences in mortality are best in countries where a system of personal identification numbers makes the computerised linkage of census and death records possible. The first part of this study is an example of the use of such linked records. It presents results on the development of mortality differences by level of education and occupational class in Finland in the period 1971-1985. Socio-economic mortality differences among middle-aged and elderly men increased in Finland during the study period. The increase was mainly due to the rapid decline of mortality from cardiovascular diseases among upper white-collar employees and men with more than secondary education. Relative socio-economic mortality differences were smaller among women than among men and remained unchanged in 1971-1985. The second part of the article discusses the problems in international comparisons of socio-economic mortality differences and summaries results from two comparative studies. The results are inconsistent: differences by level of education among men were found to be similar in six countries included in the comparison, whereas marked variation was found in the ratios of the mortality of manual workers to the mortality of non-manual workers. PMID- 8434267 TI - Gender differences in health perceptions and their predictors. AB - This study explored the degree to which risks embedded in the social construction of gender roles and personality traits explained gender differences in health perceptions and reporting among mild hypertensive patients (134 women and 104 men) under the same treatment regime. Compared with men, women were less educated, less likely to be employed, less happy, more distressed, less satisfied with family functioning, and had a weaker sense of coherence. Twice as many women as men evaluated their health as 'poor', and on average reported 2.6 more symptoms than men. These gender differences largely disappeared when unhappiness, distress, and sense of coherence were controlled. While education attainment, employment, and satisfaction with family functioning decreased gender differences in some half of the symptoms, multivariate analysis suggested that unhappiness, distress, and the sense of coherence are far better predictors of gender differential health perceptions. It is suggested that beyond biological predispositions, women's health is in double jeopardy by gender role related risks, which affect morbidity both directly through immunology system and indirectly through health perceptions. PMID- 8434268 TI - Anthropology and AIDS: the cultural context of sexual risk behavior among urban Baganda women in Kampala, Uganda. AB - One hundred and thirty Baganda women (65 HIV antibody positive and 65 HIV antibody negative), recruited from the Makerere University-Case Western Reserve University Collaborative Pediatric follow-up clinic in Kampala, Uganda were interviewed about cultural rules and norms for sexual behavior and HIV-specific risk behaviors. Interviews were analyzed for themes related to sexual risk, cultural rules regarding sex, and individual sexual practices. Statistical relationships were tested using chi 2 and t-test statistics. The mean age of the women was 21 years (range 15-30). Despite sexual norms prohibiting sex for women outside marriage, subjects reported that there are certain circumstances when a woman may take other partners, including economic need, desire for greater sexual satisfaction, or revenge on a husband with other partners. Cases were more likely to state that women may have outside partners for economic reasons (P < 0.05) and that women have outside partners for sexual satisfaction (P < 0.01). Women interviewed for this study are complying with Ugandan AIDS control messages to 'zerograze' and 'stick to one partner'. Fear of AIDS remains high, however, because women fear that their partners have not responded to risk reduction messages. Of those women stating fear of AIDS, 57% of cases and 62% of controls based their fear on their perceptions of their partners' activities. Therefore, women feel that they remain at risk of infection despite their own behavior change. We find that, while the potential for risk reduction is high for these women, cultural norms permitting males to have multiple partners limit a woman's ability to control her risk reduction. Important conclusions are: (1) a focus on women's behavior alone is not sufficient as both partners must respond to risk reduction messages; (2) knowledge about AIDS is not sufficient to achieve change in sexual behavior because sexual behavior is linked to economics, gender relations, and other complex socio-cultural factors; and (3) a study of Baganda male sexual values and behavior is urgently needed. PMID- 8434269 TI - Socioeconomic status and physical health, how are they related? An empirical study based on twins reared apart and twins reared together. AB - This investigation used the powerful combined twin and adoption design to assess the validity of three different hypotheses--social causation, childhood experiences, and health selection--on the origin of the association between socioeconomic status (SES) and health. The sample contains 99 pairs of monozygotic twins reared apart, 166 pairs of monozygotic twins reared together, 238 pairs of dizygotic twins reared apart, and 221 pairs of dizygotic twins reared together, who completed questionnaire items concerning their SES and health status. Genetic effects, environmental effects unique to the individual, as well as environmental effects shared by twins were involved in mediating the associations between SES and health. However, the relative importance of these effects varied for the different associations depending on the measures of health and SES respectively. The results indicate that social causation, childhood experiences, and health selection may all be important for the association between SES and health. It is argued that these hypotheses are not contradictory, rather the relationship between the complex dimensions SES and health may be explained by several different causes. PMID- 8434270 TI - Recent trends in sex mortality ratios for adults in developed countries. AB - This paper analyzes changes in sex mortality ratios between 1979 and 1987 for adults in 23 developed countries. (A sex mortality ratio is the ratio of male to female death rates.) Previous analyses have shown that during the mid-twentieth century sex mortality ratios increased for all adult age groups. During the 1980s sex mortality ratios continued to increase for 25-34 year olds, but showed mixed trends for other adult age groups. For example, for older adults aged 55-64, sex mortality ratios increased in Southern and Eastern European countries and Japan, but sex mortality ratios decreased in Northern European and Anglophone countries. Trends in several causes of death contributed to these trends in sex mortality ratios. For example, for 25-34 year olds, increases in men's suicide rates and HIV or AIDS mortality contributed to the increases in sex mortality ratios. For older adults, it was hypothesized that decreasing sex differences in cigarette smoking in recent decades would result in decreasing sex differences in lung cancer and ischemic heart disease mortality during the 1980s. The predicted decrease in sex differences in lung cancer mortality was observed in many countries; women had more unfavorable lung cancer mortality trends than men in the Anglophone countries and Northern and Central Western European countries. In contrast, very little evidence was found for the predicted decrease in sex differences in ischemic heart disease. The paper presents additional data concerning the contributions of trends in specific causes of death to changes in sex mortality ratios and briefly reviews evidence concerning probable causes of the observed mortality trends. It appears that recent trends in sex mortality ratios have been influenced by changing sex differences in smoking and a variety of additional factors, such as the effects of improvements in health care interacting with inherent sex differences in vulnerability to ischemic heart disease. PMID- 8434271 TI - Social and epidemiological aspects of guinea worm control. AB - Dracunculiasis prevention should be simple: in a population at risk, everyone may be protected by the filtration of drinking water. The research described in this paper allowed the authors to follow the acceptance of new information by villagers in nine localities in Mali. Two strategies were studied: safe water supply (bore-hole or cement lined wells) plus health education on the one hand, and health education alone (based on filtration) on the other. Safe water supply is undoubtedly an effective strategy whereas the success of the health education intervention is uncertain. This experience showed that health education as the only means of control failed due to a lack of social cohesion or of coordinated group-action. Also, when dracunculiasis control is not a population's priority goal, the constraints on systematic filtration are too great and a tendency to discontinue the filtration process occurs. On the other hand, when dracunculiasis is considered to be a serious problem by the population, new information about systematic filtration is better assimilated and leads to behavioural changes. In order that the goal of eradicating dracunculiasis by 1995 should not be an utopic dream, it is necessary to prioritize the allocation of clean rural water supply projects only to those endemic villages where the conditions that allow for health education to be successful are met. PMID- 8434272 TI - Experiences of Australian mothers who gave birth either at home, at a birth centre, or in hospital labour wards. AB - In order to compare their antenatal education levels, reasons for choosing the birthplace, experiences during labor and childbirth, analgesia, satisfaction with birth attendants and others present, and related attitudes 395 Sydney-area mothers were recruited within one year of giving birth. Five sources were used to obtain mail-questionnaire responses from 239 who gave birth in a hospital labor ward, 35 at a birth centre, and 121 who chose to give birth at home. Homebirth mothers were older, more educated, more feminist, more willing to accept responsibility for maintaining their own health, better read on childbirth, more likely to be multiparous, and gave higher rating of their midwives than labour ward mothers, with birth-centre mothers generally scoring between the other two groups. As well, homebirth and birth-centre mothers were more likely to feel the birthplace affected the bonding process and were less likely to regard birth as a medical condition than labour-ward mothers. In regression analysis birth venue (among other variables) significantly predicted satisfaction with doctor, if present during labour and delivery, and five variables correlated with birth venue significantly predicted satisfaction with midwife, husband/partner, and other support person. Findings are discussed in the light of the current struggle between medical and 'natural' models of childbirth. PMID- 8434273 TI - Ensuring access to health care with the introduction of user fees: a Kenyan example. AB - Many developing countries are considering or in the process of implementing user fees for government health care services. These fees have the benefit of generating much needed revenue and discouraging unnecessary utilization, but have the potential negative effect of excluding low income individuals from necessary medical care. In 1989, the Ministry of Health of the Government of Kenya briefly implemented user fees for government facilities which included a system for waiving fees for low income patients. This paper examines how that system might have worked in theory and how it worked in practice. Survey data from three districts in Kenya are used to estimate the percentage of health center outpatient fees that may need to be waived to avoid undue burden on low income households. The percentage of outpatient fee exemptions range from 11 to 34% depending on the district and the criterion used to determine ability to pay. This paper then assesses the extent to which ability to pay can be determined by readily obtainable information on patients' socio-economic characteristics. It is shown that these characteristics do predict ability to pay, but not with the degree of accuracy necessary to use as the sole criteria for granting exemptions. Thus, although the evidence from Kenya indicates that the level of outpatient fees could be paid by the majority of the population without undue burden, a minority would require fee exemptions. The main obstacle to implementing a system of exemptions is the inability to easily identify those unable to pay. PMID- 8434274 TI - The Latin American trial of psychosocial support during pregnancy: a social intervention evaluated through an experimental design. AB - Perinatal health problems are a public health priority in Latin America. Among the identified risk factors, psychological and social conditions play a crucial role. However, care during pregnancy and delivery in the region is usually hospital-centered and does not address women's psychological and social conditions. The preeminence of research on perinatal health, along with the necessity for testing interventions that represent alternative models to improve women's health, gave the Latin American Network for Perinatal and Reproductive Research grounds to develop a multicenter randomized controlled trial to evaluate a program of social support and health education during pregnancy. The conceptual framework for this study was based on an ecological model of social support, i.e. a model in which social support and health education play a synergistic role and are meant to modify stressful situations and negative health-related behaviors. The target population consisted of women attending obstetric hospitals before the 22nd gestational week, at high psychological and social risk (n = 2236). The intervention consisted of four to six home visits, carried out by social workers, and had four main components: the reinforcement of pregnant women's social support network, emotional support, health education, and the improvement of health services utilization. The main foci of the intervention were determined after an ethnographic study was carried out to identify stress-producing situations and needs for support during pregnancy. Besides the home visits, the program also offered a hot-line, an office in the hospital, a specially designed poster and booklet, and a 'guided tour' of the health institution. Since this was a multicenter trial, the program's standardization was a crucial methodological aspect that was achieved through the training course for the home-visitors team. Biological and psychosocial outcomes were measured in both experimental and control groups at the 36th week of gestational age, post-partum and at the 40th day after delivery. The attributes of the multicenter population showed an important variability, reflecting differences in the countries or hospitals' population prevalent attributes. The results of the program's implementation were analyzed, demonstrating that home visitors adapted topics discussed during the interviews to the women's conditions and the stage of pregnancy during which the visit took place.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8434275 TI - Correlates of AIDS knowledge in samples of the general population. AB - Eighty studies presenting original research are reviewed to explore the correlates of AIDS knowledge in samples of the general population. Results from these studies indicate that being highly educated, young or white increases the chances of being knowledgeable about AIDS and that a relationship exists between strong religious beliefs or conservative political convictions and low AIDS knowledge. Other social or demographic variables appear to have little effect on AIDS knowledge. Evidence from these studies is divided between findings indicating no association and those showing some relationship between low AIDS knowledge and high level of concern. Restrictive attitudes toward persons with AIDS are associated with low level of knowledge. The literature examining the correlates of AIDS knowledge in samples of the general population is characterized by an abundance of studies with small convenience samples of adolescents or students. Larger and more representative samples of the general population tend to confirm the results of the less methodologically sound convenience samples. However, future studies should take into account potential confounders when examining the relation between knowledge and explanatory variables to assess the nature and reliability of purported associations. PMID- 8434276 TI - Oral rehydration therapy--qualitative studies of balance between pragmatism and scientific rigour in managing diarrhoea. AB - In the experience of the author, oral rehydration therapy has proven effective at home, in the ambulatory and in the institutional care setting. A series of anecdotal reports on the successful use of oral rehydration on refugees, in famine and poverty, on medical students, prisoners, and the well-off people of western countries, is presented. The essential principles of oral rehydration are identified and we show how these can be adapted to a particular health care setting. A clear understanding of local attitudes and beliefs about diarrhoea is essential to professional health workers if they are to act as agents of change. PMID- 8434277 TI - Excess mortality among the unmarried: a case study of Japan. AB - Recent research has demonstrated that mortality patterns by marital status in Japan are different from corresponding patterns in other industrialized countries. Most notably, the magnitude of the excess mortality experienced by single Japanese has been staggering. For example, estimates of life expectancy for the mid-1900s indicate that single Japanese men and women had life expectancies between 15 and 20 years lower than their married counterparts. In addition, gender differences among single Japanese have been smaller than elsewhere, while those among divorced persons have been unanticipatedly large; and, the excess mortality of the Japanese single population has been decreasing over the past few decades in contrast to generally increasing differentials elsewhere. In this paper, we use a variety of data sources to explore several explanations for these unique mortality patterns in Japan. Undeniably, the traditional Japanese system of arranged marriages makes the process of selecting a spouse a significant factor. Evidence from anthropological studies and attitudinal surveys indicates that marriage is likely to have been and probably continues to be more selective with regard to underlying health characteristics in Japan than in other industrialized countries. However, causal explanations related to the importance of marriage and the family in Japanese society may also be responsible for the relatively high mortality experienced by singles and by divorced men. PMID- 8434278 TI - Life satisfaction and health in cancer patients, orthopedic patients and healthy individuals. AB - Life satisfaction (LS) is one of a set of constructs defining quality of life. Previous studies showed that LS was sometimes related to health and sometimes not. The study was designed to examine the relation of LS as a general construct to satisfaction in specific domains. We assumed that there is a tendency to maintain an acceptable level of LS even under stressful and threatening conditions, that it is related to optimism and that the likelihood of attaining satisfaction in a particular domain affected the selection of domains on which LS is based. We expected that in cancer patients LS would be related to more domains but not to health. The study was done with 55 head-and-neck cancer patients, of all stages and grades of tumor; 51 orthopedic patients, victims of accidents with good recovery chances; and 55 healthy individuals. The healthy individuals and orthopedic patients were matched (in terms of group values) to the cancer patients in age, gender and education. Single-item measures of LS and optimism, and a questionnaire with 49 multiple-choice items assessing adjustment in 13 domains were administered to all subjects. The results showed that in cancer patients LS was related to most domains but not to health and not to optimism, whereas in the other groups it was related to few domains including health, and also to optimism. The findings support the tendency to maintain LS with the materials available to the individual, and show that health is related to LS only if its maintenance or attainment are realistic goals. Thus, both bottom-up and top-down theories of LS are supported. PMID- 8434279 TI - Geographic patterns of low birth weight in Hawaii. AB - This study examines areal variations in low birth weight, using the census tract as the unit of analysis. Reports from the 1980 U.S. census were used to develop summary indicators of environmental and socio-economic conditions, including poverty, employment, education and crowding, for 155 census tracts in the state of Hawaii. Maternal socio-demographic, prenatal care utilization, and medical risk indicators and low birth weight percentages for resident, single live births were extracted from the Hawaii 1979-1987 vital record live birth files and aggregated by census tract. Multiple regression analysis was used to develop a model that predicted 61% of the variation among census tracts in the percentage of low birth weight. Patterns of low birth weight were primarily associated with ethnic patterns of maternal residence and single marital status. There was no association between inadequate prenatal care and low birth weight at the census tract level. PMID- 8434280 TI - Public attitudes to charging for some National Health Service services. AB - This report describes the views of members of the public to proposals to charge for a given list of NHS services for which no charges are currently made. The questions were part of a survey conducted in Cardiff in 1986. The majority of respondents would agree with the suggested charges being levied. This agreement spanned all sections of society. Despite the majority in favour, the sample was divided with a third of respondents being strongly for nearly all the charges and a quarter being strongly against all or all but one of the charges. Most respondents to the survey are judging each charge as a separate issue rather than indicating either approval or disapproval for all cases. If charges for services were to be introduced there could be majority agreement but each charge would have to be considered as a separate issue. PMID- 8434281 TI - Patterns of dentist location: Lansing, Michigan 1950-1991. AB - Most literature on the location and distribution of medical professionals, particularly in the U.S., has concentrated on the locational patterns of physicians, even though dentists are also important providers of health care. During the last 40 years, dentists in Lansing, Michigan have moved their offices away from traditional downtown locations to other areas of the city, primarily along commercialized arteries leading out of the city core. The changes in dentist location have mainly been the result of older dentists retiring from the downtown area and new, presumably younger dentists locating in other sections. Dentists, like physicians, tend to cluster together, particularly in buildings occupied by other medical and dental professionals. Lansing dentists do not appear to locate their offices on the basis of population characteristics. It is suggested that future research consider the effects of city size on the distributional patterns of all health care professionals. PMID- 8434282 TI - Fatness and obesity among married men at lower risk for mortality and morbidity may be due to less physiological arousal. PMID- 8434283 TI - Munchausen syndrome by proxy: social work's role. AB - Munchausen syndrome by proxy is the diagnosis used to describe a variation of child abuse whereby the parent or adult caregiver fabricates a medical history or induces symptoms in the child, or both, resulting in unnecessary examinations, treatments, hospitalizations, and even death. This article reviews the assessment procedures, provides case studies, and describes family dynamics of the syndrome. The authors make recommendations for team management of the child-family system and recommendations for social workers. They propose broadening the assessment of the family on the basis of knowledge of the widespread physical and economic oppression of women and children in our society. PMID- 8434284 TI - Effect of insurance status on pain medication prescriptions in a hematology/oncology practice. AB - To determine whether insurance status (payer class) affects the amount and type of pain medication prescribed, and whether patients in those groups without prescription drug coverage received lower-cost medications, a case-control study with retrospective chart review was initiated in a university-based hematology/oncology practice in northwest Louisiana. Charts of 710 active patients among all insurance groups (private insurance, Medicare, Medicaid, State Hospital System) were analyzed to determine insurance status, pain medication (amount and type), and diagnosis. The proportion of Medicaid patients receiving pain medications was significantly increased in relation to their representation in the practice when compared with Medicare patients, patients with private insurance, uninsured patients whose health care costs were provided by the State Hospital System, and the overall patient population. Medicaid patients, especially those with solid tumor malignancies, received the most expensive class of pain medications at a significantly higher rate than other patients. In the studied population of hematology and oncology patients, there is a significant difference in the amount and type of pain medications prescribed between patients with prescription drug coverage (Medicaid) and those without (all other groups including those covered by the statewide system). We propose that consideration be given to alternative methods of financing prescription medications for medically indigent patients. PMID- 8434285 TI - Advance directives on hospital admission: a survey of patient attitudes. AB - A survey of 200 outpatients using an anonymous, self-administered questionnaire revealed that 18% had already completed an advance directive. Only 5% had received information concerning advance directives from their physicians. Eighty seven percent stated they would not be offended if, on admission to the hospital, they were to be asked whether they had completed a living will. Eighty-eight percent would view such a policy as showing evidence of positive concern by the hospital on their behalf. Only 2% consistently gave a negative response to a proposed policy of hospitals providing information concerning advance directives on admission, and a similar percentage was totally opposed to their use. Of those who had completed an advance directive, 50% had secured the only copy in a safety deposit box. This information, as well as the Patient Self-Determination Act of 1990, which will as of December 1, 1991 require hospitals to provide patients with information about advance directives, creates a new framework for the more efficient use of these important but underused documents. PMID- 8434286 TI - Feeding gastrostomy: a critical review of its indications and mortality rate. AB - Gastrostomy can be a valuable adjunct to patient care, and percutaneous endoscopic gastrostomy is often considered the method of choice for gastrostomy placement. As with all surgical procedures, however, patient selection is important no matter how the gastrostomy is placed. In a retrospective review of 125 randomly selected patients having gastrostomy tube placement, there were certain groups of patients who received virtually no benefit from gastrostomy and may even have died sooner due to gastrostomy placement. The leading indication for gastrostomy placement was neurologic debilitation; the procedural mortality rate for these patients was 28%. However, patients with pulmonary cachexia or metastatic cachexia had much higher mortality rates: 90% and 37%, respectively. We believe patient selection has been imperfect and that certain patients should not have a gastrostomy tube. These patients suffer the moral indignation of persistent intervention and often die without receiving any real benefit. PMID- 8434287 TI - Mesenteric, omental, and retroperitoneal cysts in children: a clinical study of 22 cases. AB - Cystic lesions of the mesentery, omentum, and retroperitoneum are rare; from 1956 to 1990, 22 patients had operative treatment for such lesions at our institution. They ranged in age from 1 month to 14 years; 75% were younger than 5 years. All had either an acute abdomen or, more commonly, a silent abdominal mass. In all cases, the histologic diagnosis was lymphangioma. Abdominal ultrasonography was done in all cases after 1977 except for two patients who had an acute abdomen requiring emergency exploration. A cystic abdominal mass was diagnosed in 94% of these cases, but the correct diagnosis of lymphangioma was made prior to surgery in only 24%. Mesenteric cysts are most common in the small bowel mesentery. Omental cysts usually occur singly and are easily resected, but multiple cysts predominate in the mesentery and retroperitoneum. Complete resection was accomplished in 82% of our cases. Two patients required partial bowel resection, and four had partial excision with marsupialization of the cysts. With a mean follow-up of 23 months, we have had three recurrences, but none necessitated reexploration. Extra-abdominal lesions, mainly cutaneous lymphangiomas, developed in two cases. Prognosis is good after surgical excision, but long-term follow-up is advisable because of the possibility of recurrence, even during adulthood. PMID- 8434288 TI - Mammographic patterns and breast cancer risk factors among women having elective screening. AB - We assessed the association between Wolfe mammographic patterns and breast cancer risk factors among 239 women who attended the Breast Evaluation Unit screening program of the Comprehensive Cancer Center of Alabama, University of Alabama at Birmingham, from November 1984 through April 1986. Evaluation consisted of a breast cancer risk assessment based on a questionnaire concerning commonly accepted breast cancer risk factors, along with a physical breast examination and mammogram. Increased age, weight, and parity were associated with a low-risk pattern; late age at first birth, alcohol consumption, and oral contraceptive use were associated with a high-risk pattern. Our findings support those of previous studies, except for those concerning use of oral contraceptives. Further exploration is needed to ascertain whether the association of oral contraceptive use with high-risk patterns indicates a pathway through which estrogens may increase the risk of breast cancer. PMID- 8434289 TI - Cutaneous melanoma in African-Americans. AB - Although cutaneous melanoma is rare in African-Americans, it continues to have a poor prognosis. We reviewed our experience with 13 African-American patients who had cutaneous melanoma diagnosed between 1969 and 1990. Eight of these 13 lesions were on the foot. These lesions were seen at a late stage, and 50% of them were more than 3 mm in thickness. Nine of these 13 patients had recurrent disease. This series of patients had a 92% 1-year and a 61% actuarial 5-year survival, with a median follow-up of 45 months. This study emphasizes the need for awareness of the occurrence of this disease in the African-American population in an effort to reduce the mortality from cutaneous melanoma. PMID- 8434290 TI - Familial acalculous gallbladder disease. AB - Four patients, all sisters, presented a long-standing history of pain in the gallbladder region and no calculi. All were first thoroughly investigated and then relieved of their symptoms by cholecystectomy. This prompted an investigation of their family over three generations, which revealed a surprisingly large number of relatives, mostly female, with acalculous gallbladder disease. Our review of various syndromes causing pain in the gallbladder region, including biliary dyskinesia, cystic duct syndrome, and chronic acalculous cholecystitis, makes a case for the existence of familial incidence of noncalculous and calculous gallbladder disease, possibly related to the disturbance of the autonomic nervous system affecting emptying of the gallbladder. PMID- 8434291 TI - Resolution of hypertensive retinopathy despite persistent high diastolic pressure. AB - Four patients with exudative retinopathy due to hypertension were observed for periods ranging from 12 to 35 months. Despite multiple drug therapy in high dosage and some clinic attendance, blood pressure was not controlled and remained severely elevated. Even though severe hypertension persisted, however, exudative phenomena disappeared and renal function remained stable during the follow-up period. Neither the pathogenesis nor the natural course of hypertensive retinopathy is yet fully understood. It is accepted that antihypertensive therapy causes gradual regression of the retinal changes of hypertensive retinopathy. There are no data concerning the natural course and progress of hypertensive retinopathy in patients with severe untreated hypertension. It is unclear why the patients in our study had complete regression of hypertensive retinopathy. PMID- 8434292 TI - Apoproteins, lipoprotein subfractions, and the risk of coronary artery disease. PMID- 8434293 TI - Chronic pancreatitis. AB - Chronic pancreatitis is caused most often by chronic excessive alcohol consumption. The disease can be diagnosed by investigations that measure function or assess morphology of the pancreas, thereby permitting a tailored management approach. In many patients, abdominal pain and steatorrhea can be managed effectively by enzyme supplementation, provided such supplements are administered in appropriate formulations and doses. Definition and correction of mechanical problems are possible by modern endoscopic approaches, and surgery plays an important role in the management of local and regional complications of the disease. PMID- 8434294 TI - Selection of oral controlled-release drugs: a critical decision for the physician. AB - Controlled-oral release dosage formulations of medications have become relatively prevalent in medicine today because of their ability to reduce noncompliance and, perhaps, to increase efficacy. However, there are many patient- and drug-related factors that may present special problems in product selection. For example, interchange of controlled-release brands that may have different absorption characteristics can result in therapeutic failure and/or toxicity. Especially in light of recent events associated with Food and Drug Administration product reviews, this paper outlines concepts that will assist physicians in making informed decisions regarding generic substitution of oral controlled-release products. PMID- 8434295 TI - Retroperitoneal reticulum cell sarcoma: a cause of paraneoplastic pemphigus. AB - A 67-year-old man had mucosal ulcerations and bullous and lichenoid skin lesions resembling those of several other patients with underlying neoplasms. Computed tomography revealed an occult retroperitoneal sarcoma. Autoantibodies pathogenic to epithelia induce this syndrome, which has been termed "paraneoplastic pemphigus." Imaging for an occult neoplasm should be considered in patients with similar mucosal and skin lesions. PMID- 8434296 TI - Transnasal endoscopic closure of anterior fossa cerebrospinal fluid fistula. AB - The anterior skull base can be approached intranasally, and the development of endoscopes and accompanying endoscopic instruments in recent years makes possible extremely precise and defined work along the ethmoid and sphenoid sinus roof. Since these areas are the most frequent locations of anterior skull base CSF rhinorrhea, it follows that the localization and subsequent closure of these defects theoretically can be accomplished in this manner. Our report and others show that closure of CSF leaks can be accomplished successfully using this procedure, with minimal morbidity and at a fraction of the cost of frontal craniotomy. In our opinion, this should become the initial procedure of choice for closure of anterior fossa CSF leaks in amenable cases. PMID- 8434297 TI - Disseminated intravascular coagulopathy due to salmonellosis precipitated by blunt trauma. AB - We have reported an unusual cause of disseminated intravascular coagulopathy (DIC) in a patient with multiple injuries from blunt trauma. The source of continued hemorrhage remained elusive despite laparotomy and thoracotomy. Bleeding appeared to resolve only after discovery and treatment of infection due to Salmonella enteritidis, which the patient had contracted during a recent trip to Mexico. PMID- 8434298 TI - Thoracic actinomycosis: an unusual childhood infection. AB - I have reported a rare case of thoracic actinomycosis in a child with a chest wall mass and pneumonic infiltrate. This case emphasizes the possibility of actinomycosis occurring in a well child with no previous dental problems, chronic lung disease, loss of consciousness, or immunocompromised status. The findings on thoracic computed tomography contributed to the early consideration of actinomycosis in the differential diagnosis. PMID- 8434299 TI - Recurrent nocardiosis in a renal transplant recipient. AB - As the case presented here illustrates, nocardiosis, like other infections in which cell-mediated immunity plays a large defensive role, can relapse after apparent cure and occasionally at times remote from the original infection. Although relapse in patients with transplants has been cited as a reason for continued prophylaxis, only a few of these cases are adequately documented. This case supports the advice of those authors who give suppressive antibiotic therapy for the duration of immunosuppression in transplant recipients recovering from infections due to Nocardia sp. Alternatively, many transplant centers are routinely using TMP/SMX chemoprophylaxis in all solid organ transplantations to prevent opportunistic infections with Pneumocystis and Listeria sp. Primary prophylaxis has also been associated with a decreased incidence of nocardial infections. PMID- 8434300 TI - Isolated cardiac metastasis from cervical carcinoma: presentation as acute anteroseptal myocardial infarction. AB - Squamous cell carcinoma of the cervix is a common malignancy, but like other genital malignancies, it rarely metastasizes to the heart, even in advanced stages. This case illustrates several points, including the presentation of a cardiac metastasis mimicking ischemic cardiac disease on electrocardiogram. The diagnosis was further suggested by cardiac echocardiogram demonstrating a large right ventricular epicardial mass. It is unusual to make this diagnosis ante mortem. PMID- 8434301 TI - Osteomyelitis due to Pseudallescheria boydii. AB - This report describes an unusual opportunistic fungal infection in an immunocompetent young man who had no cutaneous involvement and whose infection was diagnosed 6 years after an accident. The unusual clinical presentation and difficulties in making a correct diagnosis are discussed and prophylactic antifungal chemotherapy is suggested. PMID- 8434302 TI - Cushing's disease with a unilateral adrenal macronodule: evolutive transition or incidental finding? AB - Cases of coexisting Cushing's disease and unilateral adrenal tumor are rare, and there are conflicting reports in the literature regarding both the pathophysiology and the incidence. We have reported the case of a patient with a biochemically inactive incidental adrenal mass in whom pituitary-dependent Cushing's syndrome developed during follow-up. Authors of past reports have suggested that transitional change is responsible for the adrenal disease. A complete review of the literature has shown that cases of coexisting pituitary Cushing's disease and unilateral adrenal tumor, although rare, are more common than was previously believed. After studying a case in which the adrenal mass was present before disease developed, we suggest that the coexistence may be incidental in some cases. PMID- 8434303 TI - Anorexia and weight loss as the solitary symptoms of choledocholithiasis. AB - Two patients are described who presented symptoms of anorexia and weight loss. Further investigation revealed choledocholithiasis in both cases, though neither patient had the classic symptoms of biliary colic, jaundice, cholangitis, or pancreatitis. The associated weight loss and anorexia resolved completely after successful bile duct surgery. These cases emphasize the need to exclude benign causes of common bile duct obstruction in patients with anorexia, weight loss, and abnormal results of liver function tests, mimicking a possible underlying malignancy. PMID- 8434304 TI - Common bile duct calculus: MRI findings. AB - Ultrasonography and CT were done in a case of obstructive jaundice. Ultrasonography showed gallstones and a dilated common bile duct; CT revealed multiple hyperdense lesions in the liver, gallbladder calculus, and a dilated common bile duct, which terminated abruptly in an apparent pancreatic mass. MRI confirmed the presence of multiple liver hemangiomas and gallbladder calculi and further revealed an obstructing common bile duct calculus as well as the absence of a pancreatic mass. PMID- 8434306 TI - Pseudohyponatremia in multiple myeloma. AB - Severe hyponatremia in any asymptomatic patient should alert the clinician to the possibility that pseudohyponatremia may be attendant with chylomicronemia or paraproteinemia. In cases of chylomicronemia, the serum is creamy, and in paraproteinemia the serum has increased viscosity. In such cases, the calculated serum osmolality will be decreased but the measured value will be within the normal range. Hyponatremia in an asymptomatic patient demands careful evaluation before institution of therapy. In addition, the presence of a normal serum sodium level in a patient with multiple myeloma should alert the clinician to the possibility that hypernatremia and hypertonicity may be present. PMID- 8434305 TI - Rhodococcus equi causing bacteremia in an adult with acute leukemia. AB - We have reported a case of isolated bacteremia due to Rhodococcus equi in an immunocompromised, non-HIV-infected patient with acute leukemia. This patient's illness demonstrates a rare presentation of an emerging opportunistic pathogen that may be potentially acquired via exposure to domestic horses or their habitat during periods of aggressive chemotherapeutic administration. The infection was successfully eradicated by treatment with erythromycin and rifampin. Counseling immunocompromised patients inclined to participate in recreational activities involving potential risks of exposure to this pathogen would seem to be a reasonable, but unproven, preventive intervention. PMID- 8434307 TI - Patient-controlled analgesia for management of pain associated with acute sickle cell crisis. PMID- 8434308 TI - Directory of pharmaceutical indigent programs. PMID- 8434309 TI - Automated percutaneous lumbar discectomy versus chemonucleolysis in the treatment of sciatica. A randomized multicenter trial. AB - A randomized clinical trial was conducted to compare the results of automated percutaneous discectomy with those of chemonucleolysis in 141 patients with sciatica caused by a disk herniation; 69 underwent automated percutaneous discectomy and 72 were subjected to chemonucleolysis. The principle outcome was the overall assessment of the patient 6 months after treatment. Treatment was considered to be successful by 61% of the patients in the chemonucleolysis group compared with 44% in the automated percutaneous discectomy group. At 1-year follow-up, overall success rates were 66% in the chemonucleolysis group and 37% in the automated percutaneous group. Within 6 months of treatment, 7% of the patients in the chemonucleolysis group and 33% in the discectomy group underwent subsequent open surgery. The complication rates of both treatment groups were low, with the exception of a high rate of low-back pain in the chemonucleolysis group (42%). The results of this trial confirm previous controlled studies on chemonucleolysis and suggest that controlled studies should be carried out before automated percutaneous discectomy can be considered a useful intervention. PMID- 8434310 TI - Vertebral 'corner' defect associated with lumbar disk herniation shown by magnetic resonance imaging. AB - Two examples of a marked defect of the corner of the vertebral body adjacent to an intervertebral disk herniation are presented. The prevalence of this finding was assessed in 43 randomly selected patients with disk herniation (at 46 levels). None of these patients had such marked vertebral defects (moderate changes at 3 levels; minor in 23). Although the defects were seen more often in younger patients, adjacent to large herniations, and in those with substantial cranial or caudal migration, these associations did not reach statistical significance. However, the site of the defect, when associated with disk migration, correlated with the direction of the migration. It is considered likely that this defect is caused by a purely mechanical effect, but its possible relationship to developmental factors is discussed. PMID- 8434311 TI - Twisting mobility of the human back in flexed postures. AB - The twisting mobility of the back was measured using an electromagnetic measuring device, the 3SPACE Isotrak, in ten healthy subjects in five postures: standing upright, in two forward-leaning positions, and two seated positions. In the forward-leaning positions the subjects flexed with mean values of 28 degrees and 53 degrees and had no difference in their active twisting compared with that experienced in the upright position. The two seated positions induced mean flexion values of 32 degrees and 44 degrees and were associated with statistically significant increases in active twisting compared with the upright position of 38% and 46%, respectively, at the level of P < 0.0001. These increases suggest that the wedge morphology of the zygapophysial joints permits greater twisting when the intervertebral joints flexed, but postural muscle action in forward leaning restricts active twisting. This study suggests a mechanism for increased vulnerability of the posterior anulus to injury when twisting is combined with flexion. PMID- 8434312 TI - Clinical validation of functional flexion/extension radiographs of the cervical spine. AB - The aim of this study was to determine the clinical validity of functional flexion/extension radiographs of the cervical spine in a defined patient population. Sixty-four adults with functional disorders of the cervical spine underwent passive flexion/extension radiographic examinations. The radiographs were analyzed using a computer assisted method to calculate segmental motion parameters, such as rotations, translations, and centers of rotation. The patients were separated into three groups based on their specific functional disorders, and their motion parameters were compared with those of a healthy population. The three groups consisted of patients with degenerative changes, those with radicular syndrome, and those with whiplash trauma. Most of the patients displayed trends toward hypomobile segmental motion. This trend is displayed more substantially in the groups with degeneration and radicular syndrome. Hypomobility in segmental rotation was significant at C6-C7 for the degenerative and radicular groups. The trauma group showed trends toward hypermobility in the upper and middle cervical levels, and the locations of the centers of rotation were shifted in the anterior direction when compared with those of the healthy population. PMID- 8434313 TI - End-plate displacement during compression of lumbar vertebra-disc-vertebra segments and the mechanism of failure. AB - Seventeen specimens of lumbar discs, attached to the caudal and cranial halves of the adjacent vertebral bodies, were subjected to a maximum compressive load of 5.5 kN in six stages. The time between each stage was about 15 seconds. At each stage of compression, a radiograph of the specimen was recorded, and the bulging of the end-plate into the caudal vertebra was measured using a displacement transducer. After compression, the ash content of a bone sample and the water content of a sample of the nucleus of the disc were measured for each specimen. Sections through the specimens were examined by light microscopic study. Eight specimens did not fail, although end-plate displacement occurred during compression. The remaining nine specimens experienced fracture or permanent deformation of the end-plate. Specimens that failed had significantly lower rigidity of the end-plate and underlying trabecular bone; this rigidity was correlated with bone ash content. PMID- 8434314 TI - Human facet cartilage: swelling and some physicochemical characteristics as a function of age. Part 2: Age changes in some biophysical parameters of human facet joint cartilage. AB - This study was aimed at investigating, in relating to aging, some of the biochemical and biophysical characteristics of the facet cartilage that determine the functional behavior of this tissue. In addition, facets and discs from the same segment were graded according to their macroscopic appearance. The proportion of severely degenerate discs was low in young subjects and increased with age; by contrast, the proportion of coarsely fibrillated and/or ulcerated facets was high in spines from young adults and remained constant throughout adulthood. Unlike discs, facets do not show an age-related loss of proteoglycans or a consequent decrease in the resistance to a compressive load. However, even in relatively young age groups (30-50 years) a high hydration was observed more often in facet joints than in cartilage from other joints studied. These characteristics are known to accompany damage of the collagen network and cartilage degeneration. Unlike normal femoral head cartilage, facet cartilage does not show a rise in fixed charge density with age. The cartilage from the superior processes (concave) is thicker than that from the inferior processes (convex) and has a higher fixed charge density. At the same time it has a higher water content, which indicates that damage occurs more frequently. PMID- 8434315 TI - Correlation between bone age and Risser's sign in adolescent idiopathic scoliosis. AB - Skeletal maturity in 86 girls with adolescent idiopathic scoliosis was determined by assessing their bone age at the hand and wrist and by the development of their iliac (Risser's sign) and ischial apophyses. The two methods were compared and a statistically significant correlation was noted, signifying that the development of the iliac and ischial apophyses is a sensitive parameter for assessing skeletal maturity in these patients. The iliac apophysis is visible on routine follow-up radiographs of these patients, so using this criterion results in a reduction of roentgen ray exposure to the patient and significant financial savings. A more sensitive method of assessing the development of the iliac and ischial apophyses is suggested. PMID- 8434316 TI - Nonlinear response analysis of the human ligamentous lumbar spine in compression. On mechanisms affecting the postural stability. AB - Basic questions regarding how extreme compressive loads can be tolerated by the spine without experiencing abnormal motions or instabilities remain unresolved. Two finite element models of the human lumbar spine were generated. The detailed model accounted for the three-dimensional irregular geometry, material and geometric nonlinearities, nonhomogeneous fiber-matrix nature of the discs, ligaments, and articulation at the facet joints. The nonlinear stability response of the model was predicted under an axial compression force (200 N to 700 N) applied at the L1 while the S1 was fixed. The effect of the presence of a combined flexion moment and a horizontal support on the response was investigated. Another nonlinear model using rigid bodies interconnected by deformable beam elements was also considered. The computed results under the axial compression loads indicated that the response is highly nonlinear with no bifurcation or limit point (critical load). The unconstrained lumbar spine is most flexible in the sagittal plane (least stiff plane). The existence of the horizontal support and the combined flexion moment significantly increased the load-bearing capacity of the lumbar spine; the lumbar spine resisted the axial compression force of 400 N with minimal displacements. Under axial compression force, the flexion moment tends to restrict the posterior translational movement of the lordotic lumbar spine, whereas the horizontal support constrains the coupled lateral motion. A slight decrease in the lordosis was predicted for the compression load of 400 N. It is postulated that the anterior location of the line of gravity of the upper-body weight is regulated to provide the required combined loads on the lumbar spine so higher compression can be tolerated by the spine at minimal energetic cost. In vivo experimental results support the validity of the model predictions. PMID- 8434317 TI - Chemonucleolysis with calpain I in rabbits. AB - Calpain I is a calcium-dependent cysteine proteinase that has been recently shown to degrade proteoglycan in vitro. The authors injected calpain I, which was purified from human red blood cells, into the intervertebral discs of rabbits. Roentgenograms showed disc space narrowing 1 week after the injection. Histologically, proteoglycan of the nucleus pulposus and anulus fibrosus decreased and notochordal cells in the nucleus pulposus almost disappeared. Biochemical data of the nucleus pulposus showed that the amounts of smaller proteoglycans increased 1 and 4 weeks after the injection. Eight weeks after the injection, histologic and biochemical data showed recovery compared with the data 1 week after injection. These findings show that calpain I is as potent an enzyme as chondroitinase ABC and has milder chemonucleolytic action than chymopapain. Regarding its possible clinical application, autogenous calpain I as purified from the patient's own red blood cells may have advantages over chymopapain and chondroitinase ABC in that it will prevent anaphylactic reaction. PMID- 8434318 TI - Urokinase for control of scar formation after laminectomy. PMID- 8434319 TI - A blinded randomized clinical trial of manual therapy and physiotherapy for chronic back and neck complaints: physical outcome measures. PMID- 8434320 TI - Family stature in idiopathic scoliosis. AB - The standing heights of 40 children with scoliosis and 110 persons from their immediate families were compared with those of a group of 349 contemporary control subjects. Skeletal bone ages and puberty ratings did not differ from normal, but the children with scoliosis were found to be significantly taller than the controls. They were also taller than their unaffected relatives, suggesting that the increased stature is not due to genetic factors alone. Scoliotic children with an affected immediate-family member were of normal height, which suggests that growth is of less etiological importance in children with a strong genetic susceptibility. PMID- 8434321 TI - Does microscopic removal of lumbar disc herniation lead to better results than the standard procedure? Results of a one-year randomized study. AB - Sixty patients with single-level lumbar disc herniation confirmed by computerized tomography were studied in a randomized prospective study. The aim was to see if there was any difference between the microscopic removal of a disc herniation and the standard procedure. All patients were operated on by the same surgeon by either method. They were all followed up by an impartial observer at 3 weeks, 2 months, 6 months, and 1 year. There were no differences between the groups regarding perioperative bleeding, complications, inpatient stay, time off work, or end result. The authors concluded that the decision to use the operating microscope may be left to the surgeon, because it had no effect on the short-term results or those at 1 year. PMID- 8434322 TI - A randomized, double-blind study to compare low-dose with standard-dose chymopapain in the treatment of herniated lumbar intervertebral discs. AB - Postoperative low-back pain and spasm are the main drawbacks of chymopapain chemonucleolysis. To investigate if low-dose chymopapain could reduce this adverse reaction, without modifying the efficacy, 118 patients with persistent low-back and radicular pain due to a lumbar disc herniation underwent chemonucleolysis. 60 patients were randomly selected to receive 2 mL of standard dose chymopapain (4,000 units) and 58 to receive 2 mL of low dose (2,000 units). The clinical outcome was assessed on study days 1, 30, and 60, and after 1 year by physicians who were unaware of the treatment, and on the basis of the patients' self evaluation. At day 60, Chemonucleolysis was rated as successful in 81% of the cases by the investigator and in 80% by the patient's self assessment. The percentage of good results was remarkably similar in the two treatment groups and this finding was confirmed after 1 year. There was some evidence that the low dose treatment resulted in less frequent postoperative back pain but the difference was not statistically significant. Moreover, a comparable incidence of acute low-back pain and spasm was observed in the two treatment groups. Low-dose chemonucleolysis appears to be as effective as the standard dose, but the use of 2,000 units does not significantly lower the postoperative back pain. PMID- 8434323 TI - Do smokers get more back pain? AB - Recently smoking has been increasingly implicated as a possible risk factor for low-back pain. One explanation for this finding is confounding by occupation. To investigate this possibility, the relationship between smoking and self-reported back pain was studied within 13 occupations. A relationship between smoking and back pain was observed only in occupations that require physical exertion. The relationship between smoking and other musculoskeletal pain also was explored. Pain in the extremities turned out to be related more clearly to smoking than to pain in the neck or the back. This suggests confounding or a general influence of smoking on pain. It is concluded that prevention of back pain could be a beneficial side-effect of anti-smoking campaigns. However, the prime target for prevention of low-back pain would have to be other factors. PMID- 8434324 TI - Initial-impression diagnosis using low-back pain patient pain drawings. AB - Patient pain drawings were blindly selected from five lumbar spine disorder categories. The drawings were classified by low-back physicians, discriminant analysis, and several computerized artificial neural network configurations. The purpose was to determine the reliability of the patient pain drawing when diagnosing low-back disorders and to delineate the pain mark patterns particular to each disorder by comparing physicians with computerized methods. The physicians averaged 51% accuracy with individual preferences for certain disorder groups. The computerized methods demonstrated comparable accuracy (48%) and more agreement in classification. Associations were found between the predicted pain patterns for each diagnostic group made by an expert and the patterns generated by computerized methods. Variances in these associations are instructive to clinicians for making accurate predictions of diagnosis from pain drawings. PMID- 8434325 TI - Comparison of spinal health indicators in predicting spinal status in a 1-year longitudinal study. AB - A 1-year longitudinal study was performed to assess and compare the predictive qualities of spinal health indicators (excluding the cervical spine) among aircraft assembly workers having at least 1 year seniority in a large assembly plant. Ten health indicators were compared to determine their sensitivity and predictive power with regard to back compensation and absenteeism in 12 months follow-up, and the presence of any limitation at work due to the back, or symptoms to the back at the end of the interval. The initial response to a self administered questionnaire was obtained from 269 male workers, of whom 205 (76.2%) completed the follow-up questionnaire. Initial prevalence of symptoms to the back was 42.3%, limitation in performing at work was 28.1%, consultation of a health professional was 7.3%, and a history of compensation for the back (ever) was reported by 30.4%. During the year of follow-up, 16 (6%) of the 269 workers initially enrolled were granted 17 compensated episodes. Of the 205 workers who responded to the follow-up, 33 (16.1%) have been absent from work (with or without compensation) because of their back. The presence, at the beginning of the study, of a limitation in performing at work or in activities of daily living and a history of compensation (ever) were the three indicators independently associated with the occurrence of compensation or absenteeism (total work disability) related to a back problem during the following year.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8434326 TI - Influence of some biomechanical factors on low-back pain in pregnancy. AB - Several biomechanical factors were recorded intermittently in 855 pregnant women from the 12th to the 36th week of gestation and were related to back pain occurrence during pregnancy. The three factors related to the development of back pain were abdominal sagittal diameter, which correlated with back pain, with a coefficient of 0.15 (P < 0.01); transverse diameter (r = 0.13, P < 0.01); and depth of the lumbar lordosis, which correlated with a coefficient of 0.11 (P < 0.01). In the group of women who were pregnant for their first time, there was a significantly lower peripheral joint laxity in the 12th week in those women who, later in pregnancy, developed back pain. These correlations suggest that back pain in pregnancy can not be explained primarily by biomechanical factors. PMID- 8434327 TI - Psychiatric illness and chronic low-back pain. The mind and the spine--which goes first? AB - Two hundred chronic low-back pain patients entering a functional restoration program were assessed for current and lifetime psychiatric syndromes using a structured psychiatric interview to make DSM-III-R diagnoses. Results showed that, even when the somewhat controversial category of somatoform pain disorder was excluded, 77% of patients met lifetime diagnostic criteria and 59% demonstrated current symptoms for at least one psychiatric diagnosis. The most common of these were major depression, substance abuse, and anxiety disorders. In addition, 51% met criteria for at least one personality disorder. All of the prevalence rates were significantly greater than the base rate for the general population. Finally, and most importantly, of these patients with a positive lifetime history for psychiatric syndromes, 54% of those with depression, 94% of those with substance abuse, and 95% of those with anxiety disorders had experienced these syndromes before the onset of their back pain. These are the first results to indicate that certain psychiatric syndromes appear to precede chronic low-back pain (substance abuse and anxiety disorders), whereas others (specifically, major depression) develop either before or after the onset of chronic low-back pain. Such findings substantially add to our understanding of causality and predisposition in the relationship between psychiatric disorders and chronic low-back pain. They also clearly reveal that clinicians should be aware of potentially high rates of emotional distress syndromes in chronic low back pain and enlist mental health professionals to help maximize treatment outcomes. PMID- 8434328 TI - Cerebrospinal fluid proteins as indicators of nerve root compression in patients with sciatica caused by disc herniation. AB - Patients with sciatica caused by lumbar disc herniation were studied to identify biochemical changes in the cerebrospinal fluid related to myelographic findings and clinical observations. One hundred forty-three patients were evaluated by myelography with regard to involvement of the dural sac and the nerve root. A medial group (20 patients) with evidence of dural sac impingement was compared to a lateral group (63 patients) and an extreme lateral group (9 patients) whose condition primarily affected the nerve root. The remaining 51 patients comprised a mixed group with involvement of both the dural sac and the nerve root. The mean cerebrospinal fluid/serum albumin ratio, cerebrospinal fluid/serum immunoglobulin G ratio, and cerebrospinal fluid total proteins showed a significantly increasing trend from the medial through the lateral to the extreme lateral groups. Patients with lateral lumbar disc herniations more often showed neurologic deficits. These results indicate that the elevated cerebrospinal fluid total protein found in the patients with sciatica is due to leaking of plasma proteins primarily from the nerve root into the cerebrospinal fluid. The cerebrospinal fluid proteins may be used as diagnostic parameters of nerve root compression, especially when surgery is a consideration or in patients in whom sciatica is unlikely. PMID- 8434329 TI - Trunk asymmetry, posture, growth, and risk of scoliosis. A three-year follow-up of Finnish prepubertal school children. AB - Several anthropometric measurements were studied for their prediction of scoliosis in 896 children (430 girls and 466 boys) who were free from scoliosis at entry. The children were examined annually from the average age of 10.8 to 13.8 years to follow up their trunk asymmetry, posture, and growth. Scoliosis developed in 24 boys and 41 girls (Cobb angle > or = 10 degrees in a posteroanterior standing radiograph) during the 3 years. In both girls and boys, trunk asymmetry measured by the forward bending test was found to be the most powerful determinant of the incidence of scoliosis. In the whole cohort the adjusted odds ratio was 1.61 and its 95% confidence interval was 1.42-1.82 per one millimeter increase in trunk hump. Using spinal pantography the degree of thoracic kyphosis in girls (odds ratio = 1.05, 95% confidence interval = 1.01 1.09, per one degree) and the degree of lumbar lordosis in boys (odds ratio = 1.07, 95% confidence interval = 1.01-1.13, per one degree) were significant predictors of future scoliosis. In the children both sexes who eventually had scoliosis, body height, sitting height, and growth of sitting height were greater than in other children, but these factors carried no statistical significance in the logistic analyses. There were differences between the prescoliotic girls and other girls in both mean age (11.8 vs 12.1 years, P = 0.02) and value (5.5 cm vs 6.1 cm/yr, P = 0.08) of peak sitting height velocity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8434330 TI - Etiology of spondylolisthesis. Assessment of the role played by lumbar facet joint morphology. AB - This study examined the role of facet joint morphology in the etiology of both degenerative spondylolisthesis and isthmic spondylolysis. To this end, the axial facet joint morphology of the lower lumbar spine in a normal population and in populations of patients with spinal stenosis or degenerative spondylolisthesis at L4-5 and in patients with isthmic spondylolysis at the L5 level were characterized. Computed tomographic scans were digitized, defining the axial morphology of the normal facet joint at five stations from proximal to distal within the joint. Assessments were made of facet joint orientation, transverse articular dimension, depth of the articular surface, and shape of the articular surface at levels L3-4, L4-5, and L5-S1. There was a gradually more coronal orientation from proximal to distal among the stations at each level, and a maximal transverse articular dimension at the level of the superior endplate of the caudad vertebra. Minimal error in the recording process at this level. In addition to the maximal joint dimension, made this level the most representative of the overall morphology and most useful for further studies. At the L4-5 level, a significantly more sagittal facet orientation was found in the degenerative spondylolisthesis group when compared to both the normal population and spinal stenosis groups (P < 0.01). At L5-S1, the only significant morphologic difference between the normal population and the patients with isthmic spondylolysis was reduced transverse articular dimension. These results support the hypothesis that patients developing degenerative spondylolisthesis are predisposed to this by a developmental sagittal orientation of the L4-5 facet joints. PMID- 8434331 TI - Clinical trial of postoperative dynamic back exercises after first lumbar discectomy. AB - Ninety-six patients who had undergone first-time discectomy for herniated lumbar intervertebral discs were consecutively randomized to two physical rehabilitation programs: a program of high-intensity, dynamic back extension and abdominal exercises with occurrence of low back pain being the limiting factor or a traditional program of mild, generally mobility-improving exercises within pain limits. Both groups underwent 14 hours of treatment during a 6-week period 5 weeks after surgery. At 26 weeks' follow-up, results indicated that patients who did the high-intensity exercises experienced greater success with regard to the patient disability-index and work capabilities. After 1 year, a trend that favored the use of intensive exercises could be observed. No differences were found in pain or objective measurements. A rehabilitation program of intensive exercises with occurrence of back pain being the limiting factor appears to increase patient behavioral support, resulting in work capacity improvements and patient self-rated disability levels. The results indicate that a 6-wk, 14-hr postoperative rehabilitation program is inadequate if objective postoperative deficit improvements are the desired goal. PMID- 8434332 TI - Intensive, dynamic back-muscle exercises, conventional physiotherapy, or placebo control treatment of low-back pain. A randomized, observer-blind trial. AB - In a randomized, observer-blind trial, 150 men and women, aged 21-64 years, with chronic/subchronic low-back pain, followed one of these three treatment regimens: 1) intensive, dynamic back-muscle exercises; 2) conventional physiotherapy, including isometric exercises for the trunk and leg muscles; and 3) placebo control treatment involving semihot packs and light traction. Eight treatment sessions were given during the course of 4 weeks, each session lasting 1 hour. The short-term effect was evaluated at the end of the treatment period and 1 month later, and the long-term effect at 6 and 12 months. The evaluations included recording of changes in pain level and assessment of overall treatment effect, which were indicated on visual interval scales. Subgroups of patients could be identified according to their treatment responses: physiotherapy was the superior treatment for the male participants, whereas the intensive back exercises appeared to be most efficient for the female participants. Patients with moderate or hard physical occupations tended toward a better response with physiotherapy, whereas intensive back exercises seemed most effective for those with sedentary/light job functions. PMID- 8434333 TI - Principles and history of neutron capture therapy. AB - Neutron capture therapy (NCT) is a form of radiation therapy using nuclides having a high propensity for capturing thermal neutrons and reacting with a prompt nuclear reaction (i.e. disintegration). If these nuclides are introduced selectively into tumor cells it is theoretically possible to destroy the tumor and to spare the surrounding normal tissue. The principles of this modality were described in 1936. First clinical trials in the USA from 1951 to 1961 using 10B resulted in failure. Since 1968 patients suffering from glioblastoma have been successfully treated in Japan by NCT with 10B and since 1987 another Japanese group has treated melanoma using NCT. The Japanese experiences and recent advances in the evaluation of tumor-affinitive boron-containing drugs have spurred interest in NCT. This article presents some basic physical notions and a historic overview of NCT that emphasizes the well documented early trials as well as some recent developments. Problems which occurred in the past now demand special efforts for a better understanding of the effects of NCT before starting new clinical trials in the next few years. PMID- 8434334 TI - Determination of the gamma-ray dose in an epithermal neutron beam. AB - Neutron beams used for Boron Neutron Capture Therapy (BNCT) are always accompanied by photons. These two irradiation components have different relative biological effectiveness. Therefore it is necessary to determine the neutron and photon absorbed dose in the mixed field separately. All gamma-ray detectors however are also sensitive for neutrons. In this work preliminary results are presented using TLD-700 chips, a Mg(Ar) ionisation chamber and a GM-counter to determine the gamma-ray component in a mixed beam of gamma-rays and neutrons. The results show a good agreement between the GM-counter and the ionisation chamber, indicating a small relative neutron sensitivity (ku) for these detectors. The sensitivity of TLD-700 for thermal neutrons however gives rise to a detector response for which a correction is necessary. The uncertainty however in the relative gamma-ray sensitivity (hu) of the detectors is at this moment too large to determine accurate values of the relative neutron sensitivities. PMID- 8434335 TI - A scintillation spectrometer for direct comparison of neutron energy spectra at high and low rates. AB - The energy spectrum of the HB11 beam at HFR, Petten, has previously been measured by proton and alpha recoil in hydrogen and helium gas proportional counters at power levels of a few kW. There is some doubt whether the spectrum remains the same at the much higher power of 45 MW required for therapeutic fluxes. In order to test this point, a scintillation detector has been developed at the Paul Scherrer Institute, Villingen, Switzerland. While the device is again based on the proton recoil reaction, a combination of mm-sized plastic scintillators and fast electronics will allow it to operate at both a few kW and 45 MW, permitting direct comparison of energy spectra at these very different power levels. Results of preliminary tests at LFR, Petten, are presented. PMID- 8434336 TI - An investigation of the possibilities of BNCT treatment planning with the Monte Carlo method. AB - The neutron fluence distribution inside two types of water phantom have been calculated with the Monte Carlo programme MCNP for the epithermal neutron beam at the Petten Low Flux Reactor. Comparison between the calculated and the measured neutron fluence distributions showed a reasonable agreement. The influence of beam and phantom geometry on the neutron fluence distribution has been calculated. An increase of the field size leads to a somewhat deeper position of the maximum of the thermal neutron fluence distribution in the cylindrical phantom. The possible use of beam modifying devices like wedges and blocks has been tested with this model. Blocks have been modelled that can locally reduce the fast neutron skin dose by 70%. PMID- 8434337 TI - Dose modification factors in boron neutron capture therapy. AB - The effective treatment depth and therapeutic ratio in boron neutron capture therapy (BNCT) depend on a number of macroscopic dose factors such as boron concentrations in the tumor, normal tissue and blood. However, the role of various microscopic dose modification factors can be of critical importance in the evaluation of normal tissue tolerance levels. An understanding of these factors is valuable in designing BNCT experiments and the selection of appropriate boron compounds. These factors are defined in this paper and applied to the case of brain tumors with particular attention to capillary endothelial cells and oligodendrocytes. PMID- 8434338 TI - Maximum therapeutic depth in thermal neutron capture therapy. AB - The effective treatment depth in boron neutron capture therapy with thermal neutrons depends on the beam aperture, heavy water concentration, boron concentrations in the tumor, normal tissue and blood, tolerance dose to normal tissue and the capillary dose modification factor. In this study a 15 cm aperture is used and the tolerance dose to normal tissue is evaluated to be 15 Gy. Human pharmacokinetic data are evaluated for BSH and D, L-BPA, the two compounds currently used in thermal BNCT. Results show that the average measured tumor to blood boron ratios and standard deviations are 1.4 (0.4) for BSH and 4.3 (1.8) for subcutaneous melanoma. Experimental dose-depth phantom results for the Musashi Institute of Technology reactor are used with expected boron concentrations to calculate the maximum therapeutic depth in the brain for a thermal neutron beam. For BPA, the subcutaneous melanoma boron concentrations are assumed for intracranial metastases, and no allowance is made for possible enhanced uptake in the dopamine and noradrenaline tracts. Results for BSH are enhanced by inclusion of the capillary dose reduction factor. Calculations show that for expected boron tumor to blood ratios, the modified advantage depth is about 4 cm and the maximum therapeutic depth is about 1.5 cm for both BSH and BPA. Typical heavy water ratios of 15% increase the treatment depth by 0.5 cm, but this is offset by the use of smaller beam aperture in practice. PMID- 8434339 TI - Quantification of relative biological effectiveness, dose modification factor and therapeutic gain factor. AB - Some basic aspects of tumor cell radiobiology are reviewed and the classical methods for the quantification of tumor response are outlined. The definition and methods for quantification of the parameters "relative biological effectiveness", "dose modification factor", and "therapeutic gain factor" are discussed. It is concluded that the first two parameters are of little practical use to compare different treatments. Only the therapeutic gain factor enables a reasonable estimation of the benefit that can be obtained from a new treatment modality. PMID- 8434340 TI - Large animal normal tissue tolerance using an epithermal neutron beam and borocaptate sodium. AB - Irradiation of the canine head following intravenous Na2B12H11SH (BSH) administration has provided useful information concerning the tolerance of skin and brain to the resultant complex form of irradiation. The effect of the boron capture reaction in skin and brain has provided estimates of the influence of the microscopic dosimetry involved. Dogs irradiated with the epithermal beam alone provided valuable insight into the relative biological effectiveness (RBE) of the fast neutron component (> 10 keV) of the epithermal beam. When compared with literature values for X-rays for the occurrence of skin necrosis in dogs, an RBE of 4.5 was derived. Previous pharmacokinetic data concerning the distribution of Na2B12H11SH (BSH) to blood and brain has been used to obtain input parameters for computer models of the microvasculature of the brain. Monte Carlo computer models were used to simulate the microscopic distribution of BSH in the normal brain. The term compound factor describes the product of the microscopic boron fission fragment dose hitting the nucleus and the relative biologic effectiveness divided by the macroscopic equilibrium dose of the boron reaction in the tissue of interest. The computed compound factor for Na2B12H11SH (BSH) in normal brain was 0.37. This factor agreed very well with the value of 0.32 obtained for the brain necrosis with the dog irradiations. The compound factor for the dog's skin was experimentally derived from the dog experiments and was equal to 0.5. PMID- 8434341 TI - RBE in fast neutron therapy and in boron neutron capture therapy. A useful concept or a misuse? AB - In high-LET radiation therapy, radiation quality and radiation quality differences have to be taken into account and specified. In fast neutron therapy, an operational approach has been adopted which is based on the concept of "clinical RBE". The paper discusses the quantities of RBE (relative biological effectiveness), reference RBE and clinical RBE and their relationship and significance in radiation therapy. In particular, the difference between the well defined RBE in radiation biology and the clinical RBE which is based on the judgement of radiotherapists is elucidated and emphasized. The clinical RBE is based on the reference RBE and implicitly includes differences in physical selectivity of the irradiation beams and clinical experience. The particular aspects of radiation quality in boron neutron capture therapy (BNCT) are due to the poor penetration of the primary beam, the inhomogeneity of the spatial distribution of 10B nuclides in the irradiated tissue and the short range of the alpha-particles emitted after neutron capture in 10B. The related problems in accounting for radiation quality in BNCT and in the applicability of the clinical RBE concept are discussed. PMID- 8434342 TI - Radiobiological considerations concerning the development of compounds for boron neutron capture therapy. AB - An analysis is carried out to evaluate the suitability of compounds for boron neutron capture therapy (BNCT). Suitable boron compounds are not necessarily those that show a high uptake ratio between tumor and healthy tissue. Compounds with lower uptake ratios, but higher concentrations in both healthy tissue and tumor, can be as effective in increasing the dose to the tumor over that of healthy tissue. In compound synthesis and evaluation, the parameters for optimization should therefore not be limited to the uptake ratio. A final assessment of the question whether and how well a given compound is suitable for BNCT can only be made after a study of its radiobiological effects on tissue. The analysis also illustrates the importance of beam quality in thermal and epithermal BNCT. An increase of adventitious radiation must be compensated by higher absolute tissue levels of a given boron compound and/or a higher uptake ratio, in order to arrive at the same dose differential between tumor and healthy tissue. PMID- 8434343 TI - Physical and tumor biological aspects and calculation model of dosage in boron neutron capture therapy (BNCT). AB - Fundamentally different aspects apply to dosage in boron neutron capture therapy (BNCT) compared to that in the case of normal radiotherapy with photons, electrons or heavy particles such as neutrons. The reason is that the latter only requires a knowledge of the stochastic distribution of the absorbed dose within cells, radiation quality and atomic composition of tissue in the regions of interest, whereas for the former the absolute concentration and microscopic distribution of 10B atoms in inter- and intracellular spaces of tumor and healthy cells is additionally of equal importance. The effects of radiation without 10B must always be superimposed on those of heavy particles resulting from neutron capture reactions on 10B atoms. Complex geometrical calculations are necessary with respect to ranges of the heavy particles smaller than a cell diameter. Apart from the direct effects of radiation without 10B, the dosage therefore depends on thermal neutron fluence, 10B concentration, its extreme inhomogeneous macroscopic distribution in the tumor tissue, the cellular localization of the 10B atoms in the large intercellular space, the cell membrane, within cytoplasm or the cell nucleus, the geometrical probability of hitting the cell nucleus, and that such a hit finally results in a cell killing, and a Poisson statistical enhancement factor, which describes the dose-effect relation for cell survival. The calculations necessary are demonstrated in the case of a normal and a tumor cell type, each with representative cell diameter and nucleus size. It is evident that the microscopic distribution of 10B atoms is one of the most critical parameters which is still insufficiently known. PMID- 8434344 TI - Proposal of a treatment protocol for boron neutron capture therapy of supratentorial malignant gliomas. AB - A proposed treatment protocol with boron neutron capture therapy using epithermal neutrons is outlined. It is intended for the initial patients with supratentorial malignant gliomas to be irradiated at the High Flux Reactor in Petten, Holland. PMID- 8434345 TI - Chlamydia pneumoniae. PMID- 8434346 TI - Concentrations of the domestic house dust mite allergen Der p I after treatment with solidified benzyl benzoate (Acarosan) or liquid nitrogen. AB - BACKGROUND: Various methods of killing the house dust mite to reduce exposure to allergen are being promoted even though complete data on their effects on allergen concentrations are not available. A study was designed to measure the concentrations of the main house dust mite allergen Der pI in homes treated with either solidified benzyl benzoate (Acarosan) or liquid nitrogen. METHODS: Der pI concentrations were measured in dust collected from mattresses, bedroom carpets, and living room carpets in 10 houses treated with Acarosan and 10 houses treated with liquid nitrogen. Samples were collected before the treatment (in July 1990) and three and six months afterwards (October 1990 and January 1991). Forty untreated houses were concurrently sampled as controls. RESULTS: Der pI concentrations were similar in the three groups at baseline. No significant fall was seen in either of the two treated groups three or six months after treatment. Concentrations in the control houses increased significantly--twofold to threefold in dust sampled from mattresses and bedroom carpets between baseline and October 1990. This increase was not seen in either of the treated groups of houses, but there was no significant difference in the Derp pI concentrations in these houses and the control houses from any site at any time point. CONCLUSIONS: Neither Acarosan nor liquid nitrogen reduced the concentrations of Der pI for as long as six months after application. A small effect was probably present as the rise seen in control houses in the three month samples was not found in the treated houses. This effect, however, is likely to be of little clinical importance and also to be transient as the trend was lost by six months. PMID- 8434348 TI - Lung function, respiratory illness, and passive smoking in British primary school children. AB - BACKGROUND: Many studies have reported a significant association between parents' smoking and reduced lung function in their children, but often the association has been found to be significant only in relation to maternal smoking. There have been few epidemiological studies on this topic in Britain. METHODS: Spirometry, in 2756 children aged 6.50-11.99 years, was carried out in a representative sample of English children, an inner city and ethnic minority sample, and a Scottish sample. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and forced expiratory flow rates of 25-75% and 75-85% (FEF25-75 and FEF75-85) were measured and standardised scores obtained separately for the English representative sample, the Scottish sample and subgroups in the inner city sample, white and Afro-Caribbean children and those originating from the Indian subcontinent. Multiple regression analyses were used to assess associations of FVC, FEV1, FEF25-75 and FEF75-85 with the passive smoking and respiratory illness, with adjustment for a large number of potential confounders. Passive smoking was defined in terms of reported number of cigarettes smoked at home by each parent. The respiratory symptoms and illnesses assessed were wheeze, asthma and bronchitis attacks, cough in the morning, and cough at any other time as reported by parents. RESULTS: Maternal smoking, but not paternal smoking, was associated with reduced FEF25-75 and FEF75-85 in boys. No association was found between passive smoking and lung function in girls, but in an analysis including both sexes the interaction of sex and parental smoking on lung function was not significant. With few exceptions, FEV1, FEF25-75 and FEF75-85 were reduced in children with wheeze and asthma attacks. CONCLUSIONS: The effect of passive smoking may depend on the close contact of a parent with a susceptible child as only maternal smoking in boys was significantly associated with impaired lung function. However, this explanation remains unsubstantiated. A parent's report of wheeze and asthma attacks in the child is reflected in reduced lung function. PMID- 8434347 TI - Relation of passive smoking as assessed by salivary cotinine concentration and questionnaire to spirometric indices in children. AB - BACKGROUND: Previous studies of the effects of passive exposure to smoke on spirometric indices in children have largely relied on questionnaire measures of exposure. This may have resulted in underestimation of the true effect of passive smoking. Biochemical measures offer the opportunity to estimate recent exposure directly. METHODS: The relation between spirometric indices and passive exposure to tobacco smoke was examined in a large population sample of 5-7 year old children from 10 towns in England and Wales. The effects of passive exposure to smoke on lung function were assessed by means of both salivary cotinine concentration and questionnaire measurements of exposure. Analyses of the relation between spirometric values and cotinine concentrations were based on 2511 children and of the relation between spirometric values and questionnaire measures on 2000 children. RESULTS: Cotinine concentration was negatively associated with all spirometric indices after adjustment for confounding variables, which included age, sex, body size, and social class. The strongest association was with mid expiratory flow rate (FEF50), the fall between the bottom and top fifths of the cotinine distribution being 6%, equivalent to a reduction of 14.3 (95% confidence limits (CL) 8.6, 20.0) ml/s per ng/ml cotinine. Salivary cotinine concentrations were strongly related to exposure to cigarette smoke at home but 88% of children who were from non-smoking households and not looked after by a smoker had detectable cotinine concentrations, 5% being in the top two fifths of the cotinine distribution. A composite questionnaire score based on the number of regular sources of exposure was as strongly related to mid and end expiratory flow rates as the single cotinine measure. The fall in FEF50 per smoker to whom the child was exposed was 51.0 (26.5, 75.5) ml/s. The relationships between the questionnaire score and forced vital capacity (FVC) or forced expiratory volume in one second (FEV1) were not statistically significant. CONCLUSIONS: These effects of passive smoking on respiratory function are consistent with the results of previous studies and, although small in absolute magnitude, may be important if the effects of exposure are cumulative. In children aged 5-7 years the use of a single salivary cotinine concentration as a marker of passive exposure to smoke resulted in clear relationships between exposure and FVC and FEV1, whereas the associations were much weaker and not significant when based on the questionnaire score. The associations between exposure and mid or end expiratory flow rates were of similar magnitude for cotinine concentration and the questionnaire score. The use of salivary cotinine concentration in longitudinal studies may help to determine the extent to which these effects are cumulative or reversible. PMID- 8434349 TI - Activated memory T helper cells in bronchoalveolar lavage fluid from patients with atopic asthma: relation to asthma symptoms, lung function, and bronchial responsiveness. AB - BACKGROUND: Bronchial mucosal inflammation and epithelial damage are characteristic features of asthma. Activation of T helper lymphocytes may contribute to this process by mechanisms including the release of cytokines promoting eosinophil infiltration and activation. METHODS: Bronchial washings and bronchoalveolar lavage fluid were obtained from 29 atopic asthmatic patients (19 with current symptoms and 10 symptom free) and 13 normal volunteers. Flow cytometry was used to assess T cell phenotype and activation status in bronchoalveolar lavage fluid and peripheral blood, and differential cell counts were made on bronchial washings and bronchoalveolar lavage fluid. Findings were related to severity of disease as reflected by symptom scores, baseline lung function, and airway responsiveness. RESULTS: CD4 T lymphocytes in bronchoalveolar lavage fluid and blood from asthmatic patients were activated by comparison with controls (CD4 CD25, median 16.8% v 8.7% for bronchoalveolar lavage fluid, and 15.3% v 8.7% in blood). Bronchoalveolar lavage fluid CD4 T cells from both asthmatic patients and controls were of memory phenotype (95.8% and 96.8% CD45RO and 1.7% and 0.4% CD45RA respectively), whereas both CD45RO and CD45RA T cells were present in blood. Patients with asthma and current symptoms showed increased bronchoalveolar T cell activation compared with patients without symptoms (CD4 CD25 18.7% v 12.3%). Within the asthmatic group there was a significant association between CD4 CD25 lymphocytes and asthma symptom scores (rs = 0.75), airway methacholine responsiveness (log PC20, rs = -0.43) and baseline FEV1 (rs = -0.39). A correlation was also found between CD4 CD25 lymphocytes and eosinophils in bronchoalveolar lavage fluid (rs = 0.48). Eosinophils in bronchoalveolar lavage fluid were increased in asthmatic patients compared with controls and the percentage of eosinophils in bronchoalveolar lavage fluid correlated with asthma symptom score. A relation was found between percentage of epithelial cells in bronchoalveolar lavage fluid and FEV1 and methacholine PC20. CONCLUSION: These results support the hypothesis that selective activation of memory CD4 T cells contributes to eosinophil accumulation, bronchial hyperresponsiveness, and symptoms in asthma. PMID- 8434350 TI - Effect of arterial oxygen desaturation on six minute walk distance, perceived effort, and perceived breathlessness in patients with airflow limitation. AB - BACKGROUND: The effect of exercise induced hypoxaemia in determining submaximal exercise capacity, perceived breathlessness, and perceived exertion is not known. The purpose of this study was to investigate the relation of these variables to the results of lung function tests and the degree of hypoxaemia during submaximal exercise in patients with airflow limitation. METHODS: Forty two patients with chronic obstructive airways disease and 28 patients with chronic severe asthma were studied. Spirometry was performed and gas transfer (TLCO) and lung volumes were measured. Submaximal exercise capacity was assessed with a standardised six minute walk test. Arterial oxygen desaturation during the walk test was monitored by a portable pulse oximeter. Patients rated their perceived degree of respiratory impairment on a Medical Research Council (MRC) breathlessness scale before the walk. Perceived breathlessness was measured by means of a linear visual analogue scale and exertion on the Borg scale after the walk. RESULTS: The six minute walk distance was strongly correlated (r value) with TLCO (0.68), peak expiratory flow (PEF: 0.55), forced expiratory volume in one second (FEV1: 0.53), transfer coefficient KCO: 0.49), age (-0.49), and forced vital capacity (FVC: 0.48) but not with oxygen desaturation during the walk. Walk distance was also correlated with the breathlessness rating on the MRC scale (-0.52), but less strongly with perceived breathlessness (-0.35) and perceived exertion (-0.30). The prediction equation for the six minute walk distance in metres (6MD) generated by multiple regression analysis was 6MD = 387 + 29.7 (TLCO) -3.1 (age) + 0.35 (PEF 1/min), which accounted for 50% of the total variance in walk distance. The mean level of saturation during the walk correlated most significantly with TLCO (0.55), FEV1/FVC (0.54), and PEF (0.48), but not with walk distance or with the rating on any of the analogue scales. The prediction equation produced by multiple regression analysis for the mean level of saturation during the walk was MEANSAT(%) = 1.3(TLCO) + 1.5 (base-line saturation) - 0.01 (6MD) - 54. CONCLUSIONS: Oxygen desaturation during the six minute walk is not related to walk distance, nor does it determine the degree of perceived exertion or perceived breathlessness in patients with airflow limitation. Patients who consider themselves the most disabled by breathlessness have the shortest six minute walk distance but do not necessarily have appreciable desaturation. PMID- 8434351 TI - Airspace size in lungs of lifelong non-smokers: effect of age and sex. AB - BACKGROUND: Emphysema is defined as the abnormal enlargement of airspaces distal to the terminal bronchiole, but the limits of normality of airspace size have never been defined. The aims of the study were to examine the effects of age and sex on airspace size in non-smokers and to define the limits of normal airspace size. METHODS: Airspace size was measured in terms of airspace wall surface area per unit volume of lung tissue (AWUV). AWUV was measured on histological sections of lung tissue with an automated scanning system, the fast interval processor. Thirty eight lifelong non-smokers were studied, 15 male and 23 female, with an age range of 21-93 years. Macroscopic emphysema was assessed semi-quantitatively on the midsagittal slice of each lung specimen. RESULTS: The relation between mean AWUV and age was negative (r = -0.78). This relation was linear, and the 95% prediction limits of its regression line were used as the limits of normality of AWUV in this sample. The AWUV-age relationship was similar in the men and women studied. Localised areas of macroscopic emphysema were found in three specimens whose mean AWUV measurements were within the normal range. CONCLUSIONS: There is a normal increase in airspace size associated with advancing age in adult lungs. The limits of normal AWUV between ages 21 and 93 years have been defined, and it is proposed that lungs with a mean AWUV below the 95% prediction limit should be considered as having emphysema. PMID- 8434352 TI - Asthma related hospital treatment in Finland: 1972-86. AB - BACKGROUND: The number of asthma related treatment periods in hospital has increased in many countries, particularly among children. The aim of the present investigation was to describe the use made of hospital services by asthmatic patients over a wide range in Finland. METHODS: A total of 255,387 treatment periods for asthma that had occurred between 1972 and 1986 was collected from the discharge register maintained by the National Board of Health (diagnosis 493, International Classification of Diseases). The numbers of admissions, days in hospital, and new occurrences of asthma were calculated by sex and age in relation to the total population at the end of each year. RESULTS: Asthma induced treatment periods in hospital in Finland were 12,860 (277 treatment periods per 100,000 inhabitants) in 1972 and 20,000 (406 per 100,000 inhabitants) in 1986. The annual increase in the number of such periods was 4.7% for men (95% confidence interval (95% CI) 3.5 to 5.9%) and 3.4% for women (2.1 to 4.7%) in relation to population. The most pronounced change was found in those aged 65 years and over, in which the number of treatment periods was found to increase annually by 7.5% (6.0 to 9.0%) for men and 4.9% (3.4 to 6.5%) for women, whereas the smallest increase was found among persons under 15 years with an annual change of 1.3% (0.2 to 2.3%) for boys and 1.1% (-0.1 to 2.4%) for girls. Although the number of asthma related treatment periods increased, that of new patients with asthma did not. An average of 114 new male asthmatic patients per 100,000 men were treated in hospitals annually between 1977 and 1986, whereas the figure for women was 115; the annual change during this 10 year period was 0.2% (-0.8 to 1.2%) for men and -0.8% (-1.8 to 0.2%) for women. CONCLUSIONS: The increase in the number of asthma related hospital treatment periods seemed attributable to the frequent treatment of the same patients. Treatment periods for persons aged 40 years or over were found to increase most, suggesting that the treatment of these asthmatic patients should be optimised and its organisation improved. PMID- 8434353 TI - Quantitative versus qualitative analysis of peak expiratory flow in occupational asthma. AB - BACKGROUND: Peak expiratory flow rates (PEF) are often used to confirm the diagnosis of occupational asthma. The records are usually analysed qualitatively, and this may lead to interobserver disagreement. In this study the diagnostic value of a qualitative assessment of change in PEF was compared with objective measures of change in PEF and the results of a specific inhalation challenge test with plicatic acid. METHODS: Twenty five patients with possible red cedar asthma recorded PEF six times a day for three weeks at work and for two weeks away from work and underwent a challenge test with plicatic acid at the end of the recording period. Patients were considered to have cedar asthma if the FEV1 after inhalation of plicatic acid was 15% or more below that on the control day. PEF was plotted against time and assessed qualitatively by three physicians. The graph was considered positive for cedar asthma if two of the three physicians agreed that PEF was lower at work than away from work. The 95% confidence interval for variation in PEF between periods at work and away from work was also obtained from 15 asthmatic patients without occupational asthma. Differences in PEF between periods at work and away from work were considered positive for occupational asthma in the patients exposed to cedar when they were outside the 95% confidence interval for variations in PEF in the 15 patients whose asthma was nonoccupational. RESULTS: Of the 25 men studied, 15 had a positive response to plicatic acid. The qualitative PEF analysis had a sensitivity of 87% and a specificity of 90% in confirming red cedar asthma as diagnosed by the specific challenge test. Among the objective methods tested, only the difference in mean PEF between the maximum PEF at weekends and the minimum PEF on working days had a sensitivity (93%) greater than that of the qualitative method and a similar specificity. CONCLUSIONS: The qualitative assessment of PEF is a good diagnostic test for cedar asthma. Only one objective method of PEF analysis proved to be slightly more sensitive than the qualitative method and similar in specificity. PMID- 8434354 TI - Cohabiting with domestic mites. PMID- 8434355 TI - Pulmonary endocrine cells of Aymara Indians from the Bolivian Andes. AB - INTRODUCTION: There is evidence to suggest that life at high altitude causes changes in the population of pulmonary endocrine cells, possibly because of exposure to chronic hypoxia. A study was made of the populations of pulmonary endocrine cells in three Aymara Indians and three Mestizos of La Paz (3600 m), Bolivia, which were compared with those in four white lowlanders. METHODS: Pulmonary endocrine cells were immunolabelled for neurone specific enolase and their two major secretory products, gastrin releasing peptide and calcitonin, and their numbers expressed per cm2 of tissue section. RESULTS: No differences in morphology, number, content, or distribution of immunoreactive cells were found when the native highlanders were compared with the lowlanders. CONCLUSIONS: If chronic hypoxia as such exerts an influence on human pulmonary endocrine cells it was not apparent in this morphological study. There was no increase in gastrin releasing peptide containing pulmonary endocrine cells, such as have previously been seen in patients with pulmonary hypertension characterised by plexogenic pulmonary arteriopathy. This may be due to the fact that in plexogenic pulmonary arteriopathy there is free migration of smooth muscle cells. Although three of the highlanders in this present study showed pulmonary vascular remodelling, this was in contrast only modest. PMID- 8434356 TI - Segregation of eosinophil proteins in alveolar macrophage compartments in chronic eosinophilic pneumonia. AB - BACKGROUND: The objective was to characterise the process and consequences of eosinophil activation and lysis in patients with chronic eosinophilic pneumonia and to compare them with those in patients with eosinophil pulmonary infiltrates from other causes. METHODS: Cells from bronchoalveolar lavage fluid of four patients with chronic eosinophilic pneumonia and four patients with eosinophilic infiltrates associated with Sjogren's syndrome, drug hypersensitivity pneumonia, postradiotherapy fibrosis, and pulmonary disease associated with graft versus host disease were studied ultrastructurally and with immunogold labelled antibodies directed against eosinophil proteins: major basic protein, eosinophil cationic protein, and Charcot-Leyden crystal protein. The concentration of eosinophil cationic protein was also measured in bronchoalveolar fluid. RESULTS: In the four patients with chronic eosinophilic pneumonia, ultrastructural studies demonstrated numerous lysed eosinophils. Further, three released eosinophil proteins were detected in distinct cytoplasmic structures in alveolar macrophages. These features were not found in the four patients with eosinophilic pulmonary infiltrates from other causes. CONCLUSION: Eosinophils in chronic eosinophilic pneumonia show signs of activation with release of eosinophil proteins. The appearance of three of these eosinophil proteins in different macrophage compartments suggests that macrophage uptake, with or without intracellular transport of released eosinophil proteins, involves separate mechanisms. This interaction does not lead to macrophage lysis, however, and one or more of these eosinophil proteins might directly affect macrophage function. PMID- 8434357 TI - Aerosolised ribavirin in patients with advanced cryptogenic fibrosing alveolitis: a pilot study. AB - BACKGROUND: A report has recently been published concerning a patient with a cryptogenic fibrosing alveolitis who showed a striking improvement after being treated with the antiviral drug ribavirin (tribavirin, Virazid). The objective of this study was to further evaluate, in an open trial, the efficacy of rivabirin in cryptogenic fibrosing alveolitis. METHODS: Ten patients (eight women) with advanced cryptogenic fibrosing alveolitis received aerosolised ribavirin (6 g/day for 15 days). Chest radiographs, lung function, and severity of dyspnoea were evaluated before and after two weeks of rivabirin treatment and also at three and 12 months. RESULTS: No differences in radiographs, lung function impairment, or severity of dyspnoea were found after treatment. No side effects were detected. CONCLUSIONS: Administration of high doses of aerosolised ribavirin has no beneficial effects in patients with advanced cryptogenic fibrosing alveolitis. PMID- 8434358 TI - Pulmonary gangrene and the air crescent sign. AB - BACKGROUND: A study was carried out to increase familiarity with the aetiology, pathogenesis, and radiographic features that characterise pulmonary gangrene. PATIENTS: Four patients with one of the disorders vasoinvasive aspergillosis, infarcted tuberculous cavity, chronic necrotising aspergillosis, and gangrene due to Pseudomonas aeruginosa were selected because they showed the variations of the typical radiographic pattern and illustrated the pathogenesis. A fifth case is also presented, in which pulmonary gangrene was simulated by the invagination of a loculated pleural effusion into the wall of a contiguous lung abscess. CONCLUSIONS: Evolution of a crescent or rim of air within a homogeneous shadow is the feature that both heralds the development and facilitates the recognition of pulmonary gangrene. It is most often the result of vascular thrombosis induced by the infecting organism. The outcome of treatment is often unfavourable, principally because of the severity of the predisposing systemic or local underlying disorder, although a delay in diagnosis, possibly due to unfamiliarity with the radiographic pattern, may have contributed to the adverse outcome in some instances. PMID- 8434359 TI - Diagnosis of pulmonary cryptococcosis by ultrasound guided percutaneous aspiration. AB - BACKGROUND: Ultrasound is useful for locating thoracic lesions and guiding biopsy procedures. The use of sonographic appearances and ultrasound guided needle aspiration has led to the diagnosis of pulmonary cryptococcosis at this hospital. METHODS: Six hundred and eight patients who had ultrasound guided lung aspirations were reviewed retrospectively and nine with documented pulmonary cryptococcosis were collected. All patients had nodules or infiltrates on the chest radiograph. The needle aspirates obtained under ultrasound guidance were stained by Riu's or Papanicolaou's method or with India ink, and six were sent for culture. Five patients also underwent bronchoscopy and biopsy. RESULTS: The nine patients had 18 pulmonary lesions, of which 15 were nodules and three infiltrates. Fifteen lesions were detectable by ultrasound, which showed the nodules to be hypoechoic with eccentrically located air echoes. In eight of the nine cases cryptococci were detected after the lung aspirates had been stained with Riu's or Papanicolaou stain or with India ink. In five of the six aspirates sent for fungal culture Cryptococcus neoformans was isolated. The diagnostic yield was higher than that of bronchoscopy. None developed post-aspiration pneumothorax or any evidence of late dissemination. CONCLUSIONS: Because they tend to be subpleural pulmonary cryptococcal lesions seem to be identifiable by ultrasound. Ultrasound guided lung aspiration is an effective, rapid, and safe method for diagnosis. PMID- 8434361 TI - A nomogram for obtaining the partial pressure of oxygen in alveolar air. PMID- 8434362 TI - Outbreak of Moraxella catarrhalis in a respiratory unit. AB - The clinical and epidemiological features of an outbreak of nosocomial Moraxella catarrhalis infection in a respiratory unit are described. Six isolates from five patients were shown to be indistinguishable by immunoblotting and restriction endonuclease analysis and different from 11 other, unrelated clinical strains. PMID- 8434363 TI - Pseudomyxoma of the pleural and peritoneal cavities. AB - Pseudomyxoma peritonei is a rare clinical manifestation of mucin producing adenocarcinomas. An extensively metastased adenocarcinoma developed a pseudomyxoma that affected not only the peritoneal cavity but also the pleura. PMID- 8434360 TI - New perspectives on basic mechanisms in lung disease. 2. Neutrophil traffic in the lungs: role of haemodynamics, cell adhesion, and deformability. PMID- 8434364 TI - Controlled trial of respiratory muscle training in chronic airflow limitation. PMID- 8434365 TI - Smoking among children and young people in Japan. PMID- 8434366 TI - [Mesenterial torsion in dogs]. AB - In the period 1984-1991, mesenteric torsion was diagnosed in ten dogs at necroscopy. The dogs were all of large breeds and were aged between 1 and 5 years. Mesenteric torsion was considered as clinical diagnosis in only one dog. PMID- 8434367 TI - [Dermatitis digitalis? Considerations in the evaluation of an intensive therapy]. AB - A piece of clinical research was performed to illustrate the recovery process of Digital Dermatitis on a chronically contaminated cattle farm. The combined effect of intensive individual treatment and an antibiotic foot-bath was examined. In addition to the classical condition recognized as Mortellaro's disease we found an aspecific form of Digital Dermatitis which failed to respond adequately to the currently recommended therapy. PMID- 8434368 TI - [ The 'new cow' slaughtered, an introduction to the new Civil Code regulations concerning hidden flaws in in animals]. AB - The obligation to guarantee the absence of hidden flaws has been omitted from the New Civil Code, which became law in 1992. It has been incorporated in the obligation to fulfil all aspects of the sales agreement. Conformity is the central theme of the new Civil Code: the delivered goods must fulfil the expectations of the purchaser. If this is not the case, then one can speak of default. The purchaser no longer has to take out a summons against the vendor within six weeks; instead, under the terms of the new Civil Code, the purchaser should inform the vendor at short notice on which of his/her entitled rights he/she will base an appeal. In the new civil Code, the possibility of demanding extra compensation ans other aspects of the sale, such as the transfer of risk, have been changed. The special emphasis on consumer purchase is new. However, all things considered, the veterinarian will find that the new regulations will not lead to substantial changes in practice. The closing sentence of the customary declaration will have to be changed to satisfy the new regulations. PMID- 8434369 TI - [The trick is to differentiate between obstinacy and powerlessness. Interview by W. Sybesma]. PMID- 8434370 TI - The effect of cyclosporine and liver autotransplantation on bile flow and composition in dogs. AB - Following liver transplantation bile formation may be influenced by hepatic denervation and cyclosporine therapy. To better establish any effect of liver transplantation on bile secretion, 6 mongrel dogs were studied: 3 underwent liver denervation by a modified autotransplantation procedure and insertion of a Thomas cannula to create a chronic duodenal fistula; 3 others had cholecystectomy and the duodenal cannula placement without manipulating the liver. One month after surgery, two control studies were done, one week apart. Then oral cyclosporine was given in doses of 5, 15, and 50 mg/kg/day for consecutive 1-week periods each. Twice on each cyclosporine regimen, after 4 and 7 days of therapy, the common duct was cannulated and bile collected for 5 h; animals were awake and fasted. The first 3 h of bile collection established basal conditions; flow was then stimulated with consecutive hour-long taurocholate infusions at 1 and 2 mumol/kg/min. In all dogs, bile flow increased as the cyclosporine dose increased, under both basal and bile salt-stimulated conditions. The increased flow primarily resulted from increased bile salt-independent flow. Cyclosporine had no effect on bile salt, bilirubin, or cholesterol secretion. Phospholipid secretion, however, decreased significantly in a dose-related manner with increasing cyclosporine in the dogs with autotransplanted livers, but not in the nontransplanted dogs. This decrease in phospholipid secretion resulted in a significant increase in the calculated cholesterol saturation of bile. Thus, cyclosporine administered orally is not cholestatic but rather increases bile flow independent of any change in bile salt secretion. Cyclosporine reduced phospholipid secretion in autotransplanted dogs, possibly related to denervation of the liver. The resultant change in biliary composition may pose a risk factor for gallstone formation. PMID- 8434371 TI - Successful intracerebroventricular allotransplantation of parathyroid tissue in rats without immunosuppression. AB - The lateral ventricle of the brain may be an immunoprivileged site for viable allografts. Allotransplanted parathyroid tissue from histoincompatible ACI rats survived and remained functional for more than 3 months in the cerebroventricles of recipient F344 rats. Microscopic examination proved that the allotransplanted parathyroid tissues retained normal histological features. In sharp contrast, when the parathyroid was placed beneath the renal capsule the allografted parathyroid tissue uniformly lost its capacity to liberate parathyroid hormone within one month, and only residual scar tissue remained at the transplantation site. After allotransplantation of parathyroid tissue into the cerebroventricle, the serum concentrations of both Ca++ and parathyroid hormone were maintained at levels similar to those before parathyroidectomy, until the time of sacrifice. During the 3-month period of post-transplantation observation, no neurological symptoms were noted in any of the F344 rats. PMID- 8434372 TI - The effect of protease inhibitor on reperfusion injury after unilateral pulmonary ischemia. AB - Reperfusion injury is a large problem in the early stage after lung transplantation. Its prevention by protease inhibitor was evaluated experimentally. Warm ischemic models were made with the left lungs of adult mongrel dogs. The time for the warm ischemic procedure was set at 2 hr, and the lungs were reperfused for 2 hr. The experimental group was divided into a control group, a UTI (urinary trypsin inhibitor) group and a GM (gabexate mecilate) group. To the UTI group, 10,000 units/kg of UTI was administrated during reperfusion, and to the GM group, 20 mg/kg of gabexate mecilate was administrated similarly. In the control group, the pulmonary vascular resistance and the lung tissue wet and dry weight ratios (W/D ratios) increased significantly, and thickened interstitium and infiltration of neutrophils were observed histologically after reperfusion. In the GM group, W/D ratios increased significantly, and histological appearances were similar to the control group. In the UTI group, the pulmonary vascular resistance increased slightly, but the W/D ratio did not increase significantly, and no changes were seen histologically after reperfusion. In the survival experiment, only two of the five dogs survived for more than seven days in the control and GM groups, while all five dogs survived for more than seven days in the UTI group. These results indicate that UTI significantly attenuates reperfusion injury, perhaps by inhibiting neutrophil proteases. PMID- 8434373 TI - Essential fatty acid deficiency increases interstitial IA-positive cells in rat kidney and accelerates renal allograft rejection. AB - Essential fatty acid deficiency has been reported to result in depletion of interstitial macrophages from rat kidneys and to permit transplantation of these kidneys across a fully allogeneic barrier without need for immunosuppression. In view of the potential for application of this phenomenon to xenografts, this study attempted to confirm the observation. Kidneys from rats fed normal or essential fatty-acid-deficient diets were transplanted to DA recipients. The donors' livers and contralateral kidneys were analyzed for their fatty acid profile in liver phospholipids, and the kidneys were examined by immunohistology for interstitial Ia(+) cells. EFAD resulted in an increase in renal interstitial Ia(+) cells detected by MRC-OX6 (anti-RT1Bpublic) from 13.5 +/- 2.9 (control diet fed rats) to 22.8 +/- 3.6 in rats on a stringent EFAD diet. Graft survival of kidneys from these EFAD rats was significantly shorter than that of kidneys from control diet fed rats. In direct contrast to the original report, this study found that EFAD caused a marked increase in renal interstitial Ia(+) cells and a reduction in allograft survival of EFAD donor kidneys. PMID- 8434374 TI - Absence of tolerance to noninherited maternal transplantation antigens expressed on skin and cornea. AB - Tolerance to noninherited maternal antigens (NIMAs) of the MHC was investigated in a rat model involving both skin and corneal transplants. Recipient animals were obtained by backcrossing F1 hybrids to parental strain animals. In one group of experiments, crosses were (DA[RT1a] x LEW[RT1(1)]) female-to-LEW male and, in a second group, (DAxPVG[RT1c]) female-to-PVG male. Homozygous backcross offspring (RT1(1/1) or RT1c/c) were putatively tolerant to DA NIMAs if the mother was a hybrid animal, having been exposed to these antigens in utero. The equivalent offspring of hybrid fathers, i.e., LEW female x (DAxLEW) male or PVG female x (DAxPVG) male, served as putatively nontolerant controls. Hemagglutinating antibody levels were measured against the class I RT1Aa antigen on days 7 and 14 after up to three consecutive subcutaneous DA strain skin grafts. Significantly lower titers were found in the putatively tolerant group 7 days after the first skin graft in the RT1a-to-RT1(1) combination (P < 0.05). Levels were not significantly different at any other time point, or at any time point in the RT1a to-RT1c combination. Tolerance to a corneal graft was not demonstrated in either the strongly rejecting RT1a-to-RT1(1) combination or weakly rejecting RT1a-to RT1c, whether or not animals were presensitized to RT1a antigens with DA skin grafts. We conclude that tolerance to NIMAs is unimportant in this clinical rat model of transplantation. PMID- 8434375 TI - The effect of hepatic ischemia-reperfusion on polyamine metabolism in some organs of the rat. AB - Hepatic ischemia was produced by clamping the portal venous and hepatic arterial blood supply to the left lateral and median lobes of the rat liver. Hepatic ornithine decarboxylase (ODC) and spermidine/spermine N1-acetyltransferase (SAT) activities in ischemic and nonischemic regions were increased and, respectively, peaked by 6 hr and 3 hr after 1 hr of hepatic ischemia. Hepatic putrescine contents in ischemic and nonischemic regions were increased and peaked by 6 hr. However, hepatic spermidine and spermine were not increased. an increase in ODC activity was also observed in the spleen and the kidney after 1 hr of hepatic ischemia. [3H]thymidine incorporation into DNA was observed in the liver and the spleen--however it was not observed in the kidney--after hepatic ischemia. PMID- 8434376 TI - A possible role for specific "anergy" in immunologic hyporeactivity to donor stimulation in human kidney allograft recipients. AB - The low immunological reactivity toward donor cells usually observed in transplant recipients has been linked to clonal deletion or suppression of alloreactive cells. However, the anergy of donor-specific reactive cells is another possibility not extensively tested until now in humans. In this case, donor-specific reactive cells would be present and eventually be activated without becoming effector cells (i.e., without secreting IL-2 or becoming cytotoxic) after donor-specific stimulation. We studied 8 patients under low-dose immunosuppressive drugs who displayed hyporeactivity toward donor stimulation. IL 2 production, proliferative response, and cytotoxic activity toward donor cell stimulation was decreased (respectively 22, 53, and 19% of response toward third party stimulation). In order to evidence anergy, we studied two activation markers (cell size increase and expression of IL-2 receptor [CD25]) in allografted recipient T cells after autologous (background), donor (experimental), and third-party cell stimulation (positive control). We showed that the percentage of CD25+ cells and the cell size increase were similar after donor or third-party cell stimulation and clearly above the background as early as days 1-2 after the beginning of the mixed lymphocyte culture. Moreover, CD4+ and CD8+ cells similarly expressed CD25 after donor or third-party stimulation. Thus, donor-specific reactive cells not only were present but could be activated without becoming effector cells. These data suggest that anergy may be an important phenomenon in allograft tolerance. PMID- 8434377 TI - Type III hyperlipoproteinemia acquired by liver transplantation. AB - A case of type III hyperlipoproteinemia (HLP) (dysbetalipoproteinemia) acquired by liver transplantation is reported. The 50-year-old female patient was referred to the Frankfurt University Hospital for orthotopic liver transplantation. She had suffered from ethylic liver cirrhosis. The donor liver showed discrete signs of steatosis. The postoperative course of the patient was satisfactory. Enzyme levels and blood coagulation tests returned to normal within thirty days. However, both cholesterol and triglycerides gradually increased from approximately 2.00 g/L to values ranging from 2.50 to 3.50 g/L within 200 days after transplantation. Cutaneous xanthomas did not develop. The patient's lipoprotein pattern met the criteria of type III HLP: the cholesterol to triglyceride ratio in very low-density lipoproteins (VLDL) was 0.64. Intermediate density lipoprotein(IDL) cholesterol was 0.48 g/L. Lipoprotein electrophoresis showed a broad beta-band, and beta-migrating particles were present in VLDL. Immunoblotting of apolipoprotein (apo) E from the patient's plasma revealed an E2/2 phenotype. However, restriction isotyping of an in vitro amplified apoE gene fragment showed the genotype of the patient to be epsilon 3/epsilon 4. These data suggest that the development of type III HLP in this patient was due to a change in the apoE phenotype from E3/4 to E2/2 after liver transplantation. PMID- 8434378 TI - Adult respiratory distress syndrome secondary to end-stage liver disease successful outcome following liver transplantation. AB - The adult respiratory distress syndrome (ARDS) complicating liver failure carries a 100% mortality. Two cases of ARDS that resolved following liver transplantation have been reported, one associated with acute allograft rejection, and the second due to sepsis. There is, however, a great reluctance to transplant these very high-risk patients. We report the first series of patients with ARDS secondary to liver failure who successfully underwent OLTX. No patient had sepsis or pneumonia. Posttransplant mechanical ventilation was required for a median of 14 days (range 6-37 days). All patients in this series are alive and well, with a follow-up of 6-15 months. This demonstrates that ARDS associated with liver failure, an otherwise uniformly lethal complication, can respond dramatically to OLTX. PMID- 8434379 TI - Rapid detection of anti-OKT3 antibodies with the Transtat assay. AB - The ability to successfully reuse OKT3, a mouse monoclonal antibody, is dependent upon the host's response to the antibody during and following the first treatment course. Antiidiotypic and/or antiisotypic antibodies may develop after exposure to OKT3. Antiidiotypic antibodies will bind OKT3, rendering it ineffective, while antiisotypic antibodies do not influence the efficacy of OKT3. A new membrane based immunoassay, Transtat OKT3 (Sangstat Medical Corp, Menlo Park, CA) detects anti-OKT3 antibodies in less than 15 min. It allows simultaneous detection of antiidiotype and antiisotype antibodies. A total of 180 serum samples were initially analyzed by ELISA; results were negative, low-titer (1:100), or high titer (> or = 1:1000). Retrospectively, these same samples were analyzed by Transtat for both anti-OKT3 (idiotype) and IgG2a (isotype). A total of 109 samples of 180 (60.6%) tested negative by ELISA and Transtat, while 71 (39.4%) tested positive. Of the negative samples by ELISA, 98 of 109 (89.9%) also tested anti-OKT3-negative by Transtat. Of the 109 specimens that were anti-OKT3 negative by Transtat, 98 (89.9%) tested negative by ELISA. There were 22 discrepant samples between the two methods; all were low-titer-positive (ELISA and Transtat). The 71 positive ELISA samples consisted of 53 low-titer (1:100) and 18 high-titer (> or = 1:1000), while the 71 anti-OKT3 positive Transtat samples consisted of 44 low-titer (1:10) and 27 high-titer (1:50). Sixty of 71 (84.5%) ELISA-positive samples were also positive by Transtat. Similarly, 60 of 71 (84.5%) Transtat-positive samples were also positive by ELISA. Of 71 patient samples positive for anti-OKT3 antibodies, 63 had an antiisotypic component present by Transtat. In conclusion, the Transtat OKT3 assay for measuring OKT3 and IgG2a antibodies offers a rapid and accurate assay for OKT3 monitoring. PMID- 8434380 TI - Diltiazem in renal allograft recipients receiving cyclosporine. AB - Of 113 cyclosporine-treated primary renal allograft recipients, 60 were randomized to receive standard therapy without diltiazem (ND) and 53 received standard therapy plus diltiazem (D). There was no difference in CsA blood levels between ND and D at all intervals between 3 and 24 months follow-up, yet the D group required 35% less CsA than the ND group (measured at 12 months). At all intervals to 24 months there was no difference in blood pressure, renal function (as measured by serum creatinine), or in the number of grafts lost between the 2 groups (ND, 4 lost; D, 3 lost). There was no significant difference in the total number of rejection episodes in the 2 groups (ND, 89 episodes; D, 71 episodes). However, the severity of rejection episodes was greater in the ND group as evidenced by a significant difference in the usage of OKT3 (ND, 17 courses; D, 8 courses of OKT3, P < 0.05). Of the biopsy-proven episodes of rejection, there were more episodes of vascular rejection in the ND group (ND, 14 episodes; D, 3 episodes, P = 0.005). The incidence of primary nonfunction was less in the D group (ND, 16 patients; D, 5 patients, P = 0.05). It was concluded that the use of diltiazem was associated with a markedly reduced requirement for CsA without any adverse effect on graft function or graft outcome. Diltiazem with CsA was associated with fewer episodes of primary nonfunction and less-severe rejection episodes and in particular fewer episodes of vascular rejection. PMID- 8434381 TI - Treatment of growth failure in children after renal transplantation. AB - Growth failure continues to be a problem in the management of children with renal failure. Children have improved growth after successful renal transplantation, but seldom have "catch-up" growth, or normal adult height. In this study we report the findings of an open label pilot study to determine the safety and efficacy of the use of recombinant human growth hormone (rhGH) in children with growth failure after successful renal transplantation. Eleven children completing at least 1 year of treatment had a mean age of 11.5 years (+/- 3.3) and mean bone age of 8.4 years (+/- 2.4), and were significantly growth-retarded (mean standard deviation score of -3.18 [+1.1]). After receiving rhGH (0.05 mg/kg) subcutaneously each day the height velocity increased from 5.2 cm/year to 8.4 cm/year (P = 0.003), and the standard deviation score improved from -3.18 to 2.23 (P = 0.004). Treatment was associated with advancement in Tanner stage from 1 to 2.8 (P = 0.004), increased bone age from 8.4 years to 10.9 years (P = 0.0002), and although it was not at the point of statistical significance, moderate decrease in creatinine clearance from 75 ml/1.73m2/min to 60 ml/1.73m2/min (P = 0.1). The advancement in Tanner stage and bone age was not out of proportion to the advancement in height age. These data suggest that children with functioning renal allografts have improved growth with supraphysiologic doses of rhGH. PMID- 8434382 TI - Hemostatic changes in heart transplant recipients and their relationship to accelerated coronary sclerosis. AB - Hemostasis was assessed in 115 steady-state heart transplant recipients (HTRs) and compared with that of 23 age-matched healthy controls and 21 age-matched patients with ischemic heart disease (IHD). Compared with the controls, the HTRs had increased levels of fibrinogen (mean and 95% confidence limits of 4.50 [4.32 4.68] g/L versus 3.47 [3.07-3.87] g/L, P < 0.001), factor VIIC (1.16 [0.98-1.21] IU/ml versus 0.99 [0.89-1.10] IU/ml, P < 0.001), and von Willebrand factor antigen (1.72 [1.58-1.88] IU/ml versus 1.00 [0.80-1.26] IU/ml, P < 0.001). HTRs had increased antithrombin III activity (P = 0.002) and protein C activity (P = 0.002), with a decrease in total protein S levels (P < 0.001) but no change in free protein S levels. Stepwise discriminant analysis of hemostatic variables showed that fibrinogen was the best discriminator of the three groups, classifying 55.6% of HTR, 40% of IHD, and 66.7% of the controls. More marked prothrombotic changes were found in HTRs transplanted for IHD than for other causes; this reached significance for prothrombin (P = 0.048), factor IX (P = 0.003), and poor fibrinolytic activity as measured by euglobulin clot lysis time (P = 0.008). The HTRs with accelerated coronary sclerosis (ACS) tended to have the most prothrombotic changes; this reached significance with factor IX (P = 0.03). In conclusion, HTRs have perturbed hemostasis; the net effects of these changes are prothrombotic. The relationship between prothrombotic changes and ACS merits further studies. PMID- 8434383 TI - Evidence that I-E-negative mice resistant to neonatal H-2 tolerance induction display ubiquitous thymic clonal deletion of donor-reactive T cells. AB - Induction of neonatal H-2 tolerance is highly efficient in most allodisparate strain combinations, with the exception of those in which neonatal recipients do not, but donor cells do, express I-E molecules. For example, less than 25% of I-E nonexpressing B10.S mice become tolerant following neonatal injection with I-E+ (B10.AxB10.S)F1 cells. It has been hypothesized that the high rate of nontolerance observed in I-E-nonexpressing neonatal recipients of injections of I E-bearing cells is caused by a failure to delete V beta 11+ cells in the immediate postnatal period. To test this possibility, we have examined V beta 11 expression and tolerogen-responsiveness among T cells of thymus and spleens harvested periodically from B10.S mice after neonatal inoculation of (B10.AxB10.S) F1 cells. We found that V beta 11+ cells were selectively eliminated within 1-2 days from the thymus glands of all recipient mice, B10.A specific proliferative T cells disappeared concordantly, and the thymus glands contained donor-derived chimeric cells. Subsequently, an increasing proportion of injected mice acquired V beta 11+ thymocytes and B10.A-responsive T cells, while losing chimeric cells. However, deletion and in vitro nonreactivity were still apparent in the majority of mice at 60 days of age. We conclude that neonatal inoculation of I-E-expressing cells established thymic chimerism and caused profound elimination of V beta 11+ cells from the thymus glands of all injected mice. Therefore, the failure of the majority of neonatally injected B10.S mice to display transplantation tolerance of B10.A antigens as adults cannot be ascribed to an inability to delete I-E-reactive thymocytes. PMID- 8434384 TI - The morphology and function of rabbit hepatocytes isolated using ethylenediaminetetraacetate. AB - The enzyme digestion technique using collagenase is used in most studies that describe hepatocyte isolation, including those in which hepatocytes are isolated for transplantation. The use of collagenase, however, has several drawbacks. We describe the use of a highly concentrated ethylenediaminetetraacetate solution for isolation of hepatocytes followed by purification using a Percoll gradient in the rabbit model. Isolated hepatocytes were then preserved at 4 degrees C for up to three days in either University of Wisconsin solution or Dulbecco's modified eagle's medium. Morphological studies of hepatocytes at 24 hr and 72 hr in either medium were performed using Papanicolaou and PAS stains of cytopreparations for the presence of glycogen. Similarly, functional studies of the preserved hepatocytes included LDH release, total tissue water content, and amount of 99m technetium mebrofenin uptake. The use of EDTA perfusion for hepatocyte isolation was highly reproducible in this model. The cell yield was comparable to that achieved previously using collagenase. The morphologic studies demonstrated pure hepatocytes with well-preserved architecture when preserved for up to three days in UW solution. Functional studies showed a statistically significant lower LDH release and total tissue water content and a higher technetium-99m mebrofenin uptake for hepatocytes preserved in UW solution. We conclude that a pure and viable hepatocyte suspension can be obtained from rabbit livers using concentrated EDTA solutions. These hepatocytes can be well preserved at 4 degrees C for up to 72 hr in UW solution, based on morphologic and functional criteria. PMID- 8434385 TI - The relationship of blood concentrations of rapamycin and cyclosporine to suppression of allograft rejection in a rabbit heterotopic heart transplant model. AB - Heterotopic heart transplants were performed on 50 New Zealand white rabbits. Groups of 5 rabbits were randomly assigned to receive, through an intravenous route, rapamycin (RAPA) or cyclosporine at the following doses: RAPA (0.05, 0.1, 0.5, and 1.0 mg/kg/day); CsA (5.0, 10.0, and 15.0 mg/kg/day). Drug vehicle and saline controls were also included. Trough blood concentrations were monitored in both RAPA- and CsA-treated groups on a weekly basis throughout the study. Biochemical assessment of renal and liver function was performed at the beginning and end of the study. Animals receiving RAPA exhibited excellent allograft survival; only two animals in the lowest dosage group (0.05 mg/kg/day) rejected their grafts. In contrast, no rejection occurred in the CsA-treated groups. Animals that rejected their grafts were maintained on the drug until the endpoint of the study was reached at 60 days posttransplant to monitor drug induced side effects. In some instances animals were sacrificed prior to this time due to infectious and other complications. No significant changes in renal or liver function were noted in the RAPA-treated group, while in the group of animals receiving the highest dose of CsA (15.0 mg/kg/day) a significant decrease in creatinine clearance was noted. A correlation was shown to exist between dose and the trough concentrations of both drugs. The whole-blood concentrations of RAPA that resulted in maximal efficacy with minimal toxicity was in the range of 10-60 micrograms/L. Rabbits having trough whole-blood concentrations of < 10 micrograms/L rejected their grafts. A much wider therapeutic range for CsA (50 300 micrograms/L) was noted. The results suggest that RAPA is as efficacious as CsA in prevention of allograft rejection in the animal model tested. The therapeutic monitoring of trough blood concentrations of RAPA, as with CsA, may be useful in guiding dosage adjustments to maximize the immunosuppressive efficacy while minimizing drug-induced side-effects. PMID- 8434386 TI - Evidence that cyclosporine causes both intracellular migration and inappropriate urinary excretion of magnesium in rats. AB - We determined the effects of cyclosporine on calcium, magnesium, and potassium metabolism in rats. Thirty Sprague-Dawley rats were randomized into three groups of ten animals each--control rats given olive oil, rats given cyclosporine at a dosage of 5 mg/kg daily, and rats given 15 mg/kg daily for four weeks. Urinary excretion of calcium, magnesium, and potassium was determined before and after 2 and 4 weeks of cyclosporine therapy. All rats were sacrificed after 4 weeks of therapy, and calcium, magnesium, and potassium concentrations in serum and tissues were determined. Serum magnesium levels were significantly lower in the cyclosporine-treated groups than in the control group, but there was no significant difference between the control and either of the cyclosporine-treated groups with regard to total urinary excretion of magnesium after four weeks of treatment. Magnesium content in the kidney, muscle, and liver was significantly higher in the 15 mg/kg group than in the control group. Calcium content in the kidney and liver was significantly higher as well. Potassium content in any type of tissue was similar in the three groups. We conclude that the intracellular migration of magnesium plays an important role--as does impaired renal conservation of magnesium--in the pathogenesis of cyclosporine-induced hypomagnesemia and that there is a discrepancy between magnesium and potassium metabolism in cyclosporine-treated rats. PMID- 8434387 TI - Protection of islets of Langerhans from antibodies by microencapsulation with alginate-poly-L-lysine membranes. AB - Microencapsulation of islets has been proposed to prevent their immune destruction following transplantation. An indirect immunofluorescence technique has been developed and used to study the permeability of the alginate-poly-L lysine microcapsules to antibodies. Wistar rat islets were incubated with the R2D6 monoclonal mouse IgM antibody against rat islets, microencapsulated, and incubated with fluorescein-labeled goat IgG antibodies against mouse IgG and IgM. For the negative controls, the first antibody was omitted or both antibodies were omitted. The positive controls included islets incubated with both antibodies before they were encapsulated. Our study demonstrated that the alginate-poly-L lysine membranes are not permeable to IgG when poly-L-lysine of molecular weights ranging from 21,000 to 390,000 are used. This simple immunofluorescence technique demonstrated the nonpermeability of the microcapsules to IgG, and could be useful for the initial evaluation of new types of membranes. PMID- 8434388 TI - Characterization of maturation and function of natural killer cells in xenogeneic (rat-->mouse) bone marrow chimeras. Evidence that rat NK cells are present and functional in a xenogeneic environment. AB - Reconstitution of B10 recipient mice, conditioned with total body irradiation (950 rads), with 40 x 10(6) untreated F344 or WF rat bone marrow cells results in stable rat stem-cell engraftment with multilineage lymphohematopoietic chimerism. We have now characterized NK cell generation, maturation, and function in fully xenogeneic chimeras (WF rat-->B10 mouse; F344-->B10 mouse). Early during xenogeneic reconstitution, rat-derived NK cells predominated in splenic lymphoid tissue, composing 14-18% of total cells at week 1 and increasing to 35.6-59.9% of total cells at week 2. By week 6, levels of rat NK cells had decreased and stabilized to that expected for normal rat (9-14.2%). The NK chimerism was reliably stable for up to 7 months following reconstitution. Most importantly, rat-derived NK cells were functional in both YAC tumor cytolysis and ADCC assays, suggesting that the xenogeneic mouse host environment was sufficient to support the generation, maturation, and function of rat-derived NK cells. PMID- 8434389 TI - Suppression of graft-versus-host disease by succinyl acetone in a rat allogeneic bone marrow transplantation model. AB - The efficacy of succinyl acetone (SA, 4,6-dioxoheptanoic acid) was explored in the allogeneic rat bone marrow transplant model of graft-vs.-host disease. Lethally irradiated Wistar Furth rats receiving Fischer 344 allogeneic bone marrow and spleen cells developed severe GVHD, resulting in mortality at 25-45 days posttransplant. Treatment for 14 days with 250 mg/kg/day of SA by Alzet osmotic pumps implanted subcutaneously 3 days before cell transfer prevented GVHD and produced long-term survivors that were allogeneic hematopoietic chimeras. SA doses below 250 mg/kg/day and treatment for less than 14 days were less efficacious. Initiation of SA therapy could be effectively delayed up to 7 days after BMT. Pharmacokinetic studies with i.v. bolus administration in normal CD rats revealed a plasma mean residence time that increased with dose and a systemic clearance that decreased with dose. Three dose-dependent half lives were apparent (ca. 7-18 min, 0.8-3 hr, and 12 hr). The s.c. bioavailability was ca. 82%. Relatively constant plasma SA levels were obtained with s.c. Alzet osmotic pumps, indicating no change in clearance with continuous exposure. Allogeneic BMT exerted no major influence upon SA clearance. These studies show that SA is a robust therapeutic agent that suppressed GVHD in the allogeneic rat BMT model under a variety of circumstances. PMID- 8434390 TI - Specific unresponsiveness in rats with prolonged cardiac allograft survival after treatment with cyclosporine. V. Dependence of CD4+ suppressor cells on the presence of alloantigen and cytokines, including interleukin 2. AB - CD4+ cells from CsA-treated DA rats with long-surviving PVG heart allografts specifically suppress the capacity of naive CD4+ cells to restore allograft rejection in irradiated DA rats, but have normal donor-specific alloreactivity in MLC. CD4+ suppressor cells from CsA-treated DA rats cultured for 3 days against either PVG or DA spleen cells lost the capacity to transfer suppression into irradiated DA rats grafted with PVG hearts and regained the ability to mediate rejection. However, these cells retained suppressor function when stimulated with donor-specific alloantigen in media supplemented with 20% Con A supernatant. CD4+ cells from CsA-treated rats cultured against either third-party stimulator cells or syngeneic cells expressing anti-PVG idiotype in media supplemented with Con A supernatant failed to maintain suppressor cell function. CD4+ cells from CsA treated rats cultured in media supplemented with Con A supernatant alone also failed to maintain suppressor function. Suppressor cell function in culture was not maintained by rIL-2. mAb to the IL-2 receptor alpha chain (CD25) prevented the maintenance of suppressor cell function in media supplemented with Con A supernatant. Con A supernatant is rich in IFN-gamma, but addition of an anti-IFN gamma mAb to the culture did not affect the maintenance of suppressor cells. These studies demonstrate that the CD4+ suppressor cell from CsA-treated rats with long-surviving grafts is short-lived; its survival is dependent upon contact with specific alloantigens and cytokines, one of which is IL-2. In the absence of cytokines and/or specific alloantigen, the CD4+ cells regain the capacity to initiate graft rejection in irradiated rats, suggesting that within the CD4+ subpopulation there is a fragile balance between cells with the capacity to suppress and effect rejection. PMID- 8434392 TI - Kidney cell-restricted recognition of MHC class I alloantigens by human cytolytic T cell clones. AB - The kidney expresses antigens not generally expressed by other cells in the body. To test the hypothesis that kidney-restricted antigens alter T cell recognition of MHC class I alloantigens, a panel of human T cell clones was established using an allogeneic kidney cell line (KCL) as the source of stimulator cells. Unexpectedly, a majority of these clones lysed the stimulating KCL in an allospecific manner but completely failed to lyse lymphoid cell targets derived from the KCL donor. Three of the KCL-reactive clones have been characterized in detail. All three are CD8+/CD4-, alpha/beta TCR,+ and their lytic activity is blocked by monoclonals to HLA class I framework determinants. Mapping studies using a panel of KCL targets, and blocking studies with allele-specific monoclonals indicated that clone 1-5 is directed to HLA-A3, clone 3-10 to HLA-B62 (putatively), and clone 5-2 to HLA-B51. Direct lysis and cold target inhibition assays demonstrated that clones 1-5 and 3-10 recognize their target class I alloantigens on KCL but not on EBV-transformed B cells or PHA-stimulated T cells. FACS analysis and HLA phenotyping excluded quantitative or qualitative deficiencies in HLA class I expression on the lymphoid cell targets as likely mechanisms of tissue specificity. These data suggest that kidney-restricted antigens may play a role in T cell recognition of MHC class I alloantigens, and they raise the possibility that parenchymal cell-restricted effector populations may contribute to rejection of renal allografts. PMID- 8434391 TI - Specific unresponsiveness in rats with prolonged cardiac allograft survival after treatment with cyclosporine. VI. In vitro alloreactivity of T cell subsets from rats with long-surviving allografts. AB - DA rats treated with a short course of cyclosporine develop specific unresponsiveness to RT1-incompatible PVG donor heart allografts. CD4+ cells, not CD8+ cells, transfer unresponsiveness to irradiated rats. However, host-derived CD8+ cells are important in reestablishing unresponsiveness. In this study, unfractionated lymphoid cells and W3/25+ (CD4+) cells from CsA-treated rats with long-surviving PVG allografts demonstrated normal alloreactivity to PVG alloantigen in the mixed lymphocyte culture and failed to suppress the proliferative response of naive W3/25+ cells to donor-specific alloantigen. MRC OX8+ (CD8+) cells did not proliferate. Sera from CsA-treated rats had no effect on the MLC reactivity of cells from CsA-treated rats, suggesting that blocking or antiidiotypic antibodies did not diminish alloreactivity. IL-2 production by W3/25+ cells from CsA-treated rats was similar to that by W3/25+ cells from naive rats. Specific cytotoxic T cells to PVG were generated in MLC, and the frequency of precursor cytotoxic lymphocytes in CsA-treated rats was similar to that in naive DA rats. In an in vitro assay testing response to idiotype, neither W3/25+ or MRC OX8+ cells from unresponsive rats proliferated. As CD4+ cells from CsA treated rats lose their capacity to adoptively transfer specific unresponsiveness unless maintained in a cytokine-rich supernatant, all in vitro assays were performed with and without added cytokines, but no change in reactivity consistent with suppression was observed in any assay. CD4+ suppressor cells had no effect on conventional in vitro assays of alloreactivity, preventing the detection of the unresponsiveness in vitro. PMID- 8434393 TI - Confirmation of graft-versus-host disease after liver transplantation by PCR HLA typing. PMID- 8434394 TI - Successful donation and transplantation of multiple organs from a victim of cyanide poisoning. PMID- 8434395 TI - Parvovirus B19 infection causing pure red cell aplasia in a recipient of pediatric donor kidneys. PMID- 8434396 TI - Rapid analysis of tumor necrosis factor-alpha mRNA expression during venoocclusive disease of the liver after allogeneic bone marrow transplantation. PMID- 8434397 TI - Liver transplantation for familial hypercholesterolemia before the onset of cardiovascular complications. PMID- 8434398 TI - Digestive tract infections in kidney and liver transplantation in a single institution. PMID- 8434399 TI - Therapeutic in vivo use of the A1-CD3 monoclonal antibody. PMID- 8434400 TI - Rejection of a kidney graft mismatched only for the HLA-C locus and an HLA-BW22 split. PMID- 8434401 TI - Use of Greenfield filters in renal transplant patients--are they safe? PMID- 8434402 TI - Disseminated intravascular coagulation in cadaveric organ donors. Incidence and effect on renal transplantation. PMID- 8434403 TI - Absence of clinical symptoms following the first injection of anti-T cell receptor monoclonal antibody (BMA 031) despite isolated TNF release. PMID- 8434404 TI - An alternative technique for in situ arterial flushing in elderly liver donors with atherosclerotic occlusive disease. PMID- 8434405 TI - Use of extracorporeal membrane oxygenation for adult respiratory distress syndrome following cadaveric renal transplantation. PMID- 8434406 TI - Osmotic pump delivery of rapamycin. PMID- 8434407 TI - The regeneration of transplanted hepatocytes within the mesenteric fat pad of mice. PMID- 8434408 TI - 15-deoxyspergualin effects in rat heart allograft transplantation--relation to dose, timing, and cyclosporine. PMID- 8434410 TI - Fluxes, doses and poisons: molecular perspectives on dominance. PMID- 8434409 TI - Prevention of rejection of transforming growth factor beta-treated rat-to-mouse islet xenografts by monoclonal antibody to tumor necrosis factor. PMID- 8434411 TI - Synapse-specific gene expression. AB - Skeletal myofibers are specialized at the site of contact between nerve and muscle, and recent studies indicate that mechanisms involved in the formation of this specialized region are similar to mechanisms used to establish specialized domains in other syncytial cells. In this review experiments are summarized that indicate that nuclei in the synaptic region of syncytial myofibers are transcriptionally distinct from nuclei in the remainder of the myofiber, and the steps used to establish synapse-specific gene expression are compared with the mechanisms used to regulate gene expression among subsets of nuclei in other syncytia, namely the syncytial blastoderm of Drosophila melanogaster and the syncytial germ line of Caenorhabditis elegans. PMID- 8434412 TI - Evolution of Salmonella O antigen variation by interspecific gene transfer on a large scale. AB - The O antigen is a bacterial surface polysaccharide made up of repeats of a short oligosaccharide. There are about 60 forms of O antigen in Salmonella, and genetic analysis indicates that these were acquired by interspecific gene transfer. PMID- 8434413 TI - The search for the familial breast/ovarian cancer gene. AB - Familial breast cancer is a very common autosomal dominant disorder in women. A predisposing gene for breast and ovarian cancer (BRCA1) has been mapped by linkage analysis to the long arm of chromosome 17. In almost all families with breast and ovarian cancer and half of those with only breast cancer, the disease is linked to this gene. The BRCA1 gene, which is also believed to be involved in sporadic breast and ovarian cancer, should soon be identified. PMID- 8434414 TI - Transgenic mice as model systems for studying gene mutations in vivo. AB - Transgenic mice carrying bacterial reporter genes have been developed to study spontaneous or induced mutations in vivo. Mutations can be analysed upon the efficient retrieval of reporter genes from mouse genomic DNA into a suitable bacterial host. These systems allow, for the first time, the direct correlation of mutational mechanisms in vivo with their ultimate physiological endpoints, for example, cancer or ageing. PMID- 8434415 TI - 'Guessmer' screening strategy applied to species with AT-rich coding sequences. PMID- 8434416 TI - Bacteriophage lambda: long-term stored stocks ready for lysis. PMID- 8434417 TI - MacConkey-II lactose agar for screening recombinant plasmids. PMID- 8434418 TI - The dichotomy between germ line and somatic line, and the origin of cell mortality. AB - The germ cells of extant animals are potentially immortal, whereas somatic cells are mortal, that is, they are able to carry out only a finite number of divisions. In this article we propose an evolutionary interpretation of these differences. We assume that germ cells of the earliest metazoans inherited immortality from their unicellular ancestor, while somatic cells acquired mortality by gaining new functions. It follows that cell mortality was under genetic control from the beginning of metazoan life. PMID- 8434419 TI - Suppression of chemotactic activity of neutrophils in hyperosmotic conditions comparable to the renal medulla: partial preservation by phosphoenolpyruvate. AB - Chemotaxis is one of the most important functions of the polymorphonuclear leukocyte (PMN). In the host defense against pyelonephritis, the renal medulla is a site of interaction between bacteria and PMNs. At this site the osmotic pressure is elevated due to a high concentration of NaCl and urea. We evaluated the in vitro chemotactic activity of PMNs under the hyperosmolar conditions created by high concentrations of NaCl and urea. This activity was suppressed by the stimulation of opsonized zymosan and formyl-methionyl-leucyl-phenylalanine. The inhibition of chemotaxis was partially preserved by phosphoenolpyruvic acid (PEP), a precursor of adenosine triphosphate (ATP), in hyperosmolar NaCl but not in urea. The intracellular content of ATP was increased by supplementing the hyperosmolar NaCl with PEP. These observations suggest that inhibition of the chemotactic activity of PMNs is due to differing mechanisms for each NaCl and urea, and that PEP may protect the PMNs against hyperosmolar NaCl by maintaining ATP content. PMID- 8434420 TI - Relation between basement membrane degradation and serum levels of laminin P1 in patients with transitional cell carcinoma of the bladder. AB - In 47 patients with transitional cell carcinoma (TCC) of the bladder, we investigated the relationship between tissue laminin distribution and serum laminin levels. The results were compared with those obtained from 6 patients with pathologically proven normal bladder mucosa as well as those obtained previously from 50 controls and 16 patients with benign bladder disorders. Interruption of the basement membrane (BM) laminin staining pattern was correlated with high serum laminin levels (r = 0.34; p < 0.01). The majority of patients with discontinuous BM laminin staining (82%) showed elevated serum laminin levels above the upper limit of normal range. In addition, the mean value of serum laminin P1 was significantly higher in patients with discontinuous BM than that in patients with intact BM (t = 3.18; p < 0.005). These data suggest that the high serum laminin levels in TCC patients are largely caused by the process of BM breakdown and loss. PMID- 8434421 TI - A proposed simplified staging system of invasive bladder tumors. AB - Staging of bladder tumors is based primarily on the depth of tumor invasion (T category) and is important to treatment planning and prognosis. The problem is that clinical evaluation by T category alone often understages the pathologic extent of disease and does not reliably predict treatment results. The current analysis suggests that the presence of a mass palpable on bimanual examination is of prognostic value and incorporation of this feature with microscopic tumor invasion may enhance the usefulness of clinical staging. PMID- 8434422 TI - Effect of different local and systemic therapy upon urinary bladder cytology. AB - 1,900 cytological analyses of urine and bladder washings were made in 127 patients with urothelial bladder carcinomas before, during and after therapy. Following transurethral resection, all patients were treated by intravesical instillation of mitomycin C or thiotepa. Because of a locally advanced bladder carcinoma, 26 patients who were not candidates for radical cystectomy were given an integrated treatment of radiotherapy and chemotherapy. Intravesical administration of mitomycin C and thiotepa as well as integrated radiotherapy and chemotherapy induce a variety of cytological effects (toxic and/or metabolical) which may lead to cytological misinterpretations in the follow-up. DNA measurements by means of single-cell spectrocytophotometry show that the cytological effects induced by the above-mentioned therapies are not accompanied by an increase in the nuclear DNA content. It is concluded that the knowledge of these induced effects is mandatory for a correct interpretation of urinary cytology in the follow-up. Considering these effects and the clinical history, bladder carcinoma recurrences during and after intravesical chemotherapy or integrated radiotherapy and chemotherapy may be detected early by urinary cytology in the hands of an experienced cytopathologist or urologist. Furthermore, alterations of the urinary cytology occur after systemic application of cyclophosphamide and under immunosuppressive therapy. PMID- 8434423 TI - Immunopathology of alkaline phosphatase isozymes in seminoma. AB - An immunohistopathological study using monoclonal antibodies for alkaline phosphatases demonstrated placental alkaline phosphatase (PLAP)-like substance in the tumor cells of 11 pure seminomas, 1 seminoma with embryonal carcinoma and 1 seminoma metastasis. Liver alkaline phosphatase (LAP) could also be demonstrated in all seminomas but a third intestinal alkaline phosphatase (IAP) was not demonstrable in any tumor. The PLAP-like substance and LAP had considerable enzyme activities. This provides two tumor markers of seminomas detectable in histopathological specimens. PMID- 8434424 TI - Alterations in the lipid composition of seminal plasma in patients with a chronic infection of the urogenital tract. AB - The lipid composition of seminal plasma was studied in 15 control subjects and 21 patients consulting for hypofertility and showing a chronic infection of the urogenital tract. In the infected patients a significant reduction in total cholesterol, HDL cholesterol and total phospholipids was noted. Moreover, there is a significant correlation between the rates of total cholesterol and prostatic acid phosphatases and the rates of phospholipids and proteins in seminal plasma. Knowing the role of lipids in the phenomena of maturation and capacitation of spermatozoa, such modifications enable us to understand better the functional anomalies of sperm observed in patients with chronic infection of the urogenital tract and also enable us to explain the effects of the infection on fertility. PMID- 8434425 TI - Color-Doppler imaging in acute scrotal disorders. AB - Eighteen patients who referred to our hospital with acute scrotal pain and swelling were evaluated with color-Doppler imaging (CDI) after the initial clinical examinations. Five of these subjects were considered to have testicular torsion as diagnosed with CDI. These diagnoses were surgically confirmed, and appropriate treatments were performed. CDI findings of 13 patients were in accordance with inflammatory pathologies (epididymitis and/or orchitis). These patients received medical treatment. The CDI diagnoses of all patients were in agreement with the final clinical diagnoses. We conclude that CDI, which is a practical, rapid and high-resolution technique, promises to be the leading and decisive scanning method in acute scrotal disorders. PMID- 8434426 TI - Physicochemical background for ambiguity of clinical recommendations in treating phosphate nephrolithiasis. AB - Efficiency of clinical recommendations for curing and prevention of phosphate nephrolithiasis founded on physicochemical investigations is unexpectedly low and apparently did not exceed 50%. We tried to consider possible physicochemical causes of this fact. For this purpose the influence of changes of urine pH and of calcium, phosphate and complexon concentrations on the probability of different precipitation phases of solid calcium phosphate has been reviewed. The importance of tendencies of changing the urine dynamic physicochemical parameters such as the precipitation induction period and the amplitude of urine pH variations in time has been shown. It was established that the probability of the existence of Ca3(PO4)2, Ca8H2(PO4)6.5H2O, CaHPO4.2 H2O and MgNH4PO4.6 H2O in urine depends on the time of its transition from the supersoluble state and is determined in the final analysis by the relationship of formation rates and solid phase dissolution rates. This was verified by experiments and by data obtained in the clinical laboratory. PMID- 8434427 TI - Cystic adrenal mass: pseudocyst associated with hemangioma. AB - We present a 70-year-old man with cystic adrenal tumor associated with hemangioma. The pathogenesis of this rare disease is discussed with special reference to its diagnosis and treatment. PMID- 8434428 TI - Seminal vesicle cyst with ipsilateral renal agenesis. AB - A case of seminal vesicle cyst with ipsilateral renal agenesis is presented. Embryology, symptomatology, diagnosis and treatment options are discussed. PMID- 8434429 TI - Polyps of the prostatic urethra. Report of four cases. AB - We described 4 cases of polyps of the prostatic urethra. Three of them had adenomatous polyp with prostatic epithelium and 1 showed polypoid urethritis. These lesions were worth noting as a cause of hematuria, dysuria or hematospermia. Polyps or papillary lesions of the prostatic urethra appear to be more common than have been suspected. Careful attention should be paid to the prostatic urethra in patients with persistent painless hematuria. PMID- 8434430 TI - Multivariate evaluation of prognostic determinants for renal cell carcinoma. AB - To clarify the relative importance of clinicopathological factors affecting survival in patients with renal cell carcinoma, univariate and multivariate analyses by Cox's proportional hazards model were performed for 121 patients undergoing nephrectomy between 1980 and 1991. The 5-year survival rate was 67% for all 121 patients. Univariate analysis revealed that distant metastasis, local invasion, venous involvement, infiltration pattern, grade, lymph node metastasis, sex, and tumor size were significantly associated with patient survival. Multivariate analysis using a method of stepwise selection revealed that presence or absence of distant metastasis is the most significant determinant (p < 0.0001) for survival, followed by venous involvement (p < 0.001), treatment period (p < 0.02) and local invasion (p < 0.02), in this order. A four-factor model of the above determinants yielded adjusted hazard ratios of 5.3 for distant metastasis (positive vs. negative), 3.7 for venous involvement (pV1a-pV2 vs. pV0), 3.9 for treatment period (1980-1984 vs. 1985-1991), and 3.1 for local invasion (pT3-pT4 vs. pT1-pT2). The present study revealed recent improvements in the patient survival and justified the clinical application of Robson's staging system implying local invasion, venous thrombus formation and distant metastasis as prognostic determinants. PMID- 8434431 TI - Prepubertal testicular tumor registry. AB - There are 327 patients in the Prepubertal Testicular Tumor Registry, and demographic data and a better understanding of the natural history and behavior of the tumors have evolved. Information on these rare tumors should be collected centrally and treatment using national protocols followed closely. Continuation of the Registry is important to help clarify the knowledge of these unusual tumors and to aid in the management of these patients through information from a large database. PMID- 8434432 TI - Carcinoma in situ of the testis and bilateral carcinoma. AB - Carcinoma in situ of the testis is being recognized with increasing frequency and may be increasing in absolute terms. The circumstances in which CIS should be suspected are well defined, and the opportunity exists of intervening before an invasive tumor is evident, thus sparing the testis. External radiation appears effective, although experience is limited. Finally, bilateral testis cancer may be increasing in frequency; although treatment plans must be individualized, the ultimate outcome remains excellent. PMID- 8434433 TI - Management of teratoma. AB - In prepubertal children, teratoma is a benign tumor, whereas in adolescents and adults, it behaves as a malignant neoplasm. Adult patients without evidence of metastases may be candidates for surveillance after orchiectomy, and those with low-volume or borderline retroperitoneal metastases thought to contain teratoma might best be managed by surgery, as teratomatous deposits do not respond to chemotherapy. Patients with larger retroperitoneal metastases may be given chemotherapy before surgery to reduce or eliminate other germ-cell elements. Teratomatous masses persisting after chemotherapy are excised by most clinicians, in part to obtain a pathologic diagnosis. In childhood tumors, inguinal orchiectomy or enucleation is sufficient if one is certain the lesion contains only teratoma. PMID- 8434434 TI - Gonadal stromal tumors, gonadoblastomas, epidermoid cysts, and secondary tumors of the testis in children. AB - Gonadal stromal tumors generally are benign and hormonally silent. When hormonally active, they may cause either virilization or feminization, posing an endocrine threat to the prepubertal boy. Accurate diagnosis is essential to differentiate those tumors that require medical management from those best treated by surgical ablation and to distinguish the benign ones from the malignant. Leukemic infiltration is the most common secondary testis tumor; others are neuroblastoma, Wilms' tumor, and gonadoblastoma. PMID- 8434435 TI - Fertility and testis cancer. AB - Patients with testicular cancer may demonstrate impaired spermatogenesis because of the disease process or as a direct consequence of treatment. For some patients, impaired spermatogenesis may resolve spontaneously, while in others, treatable etiologies may be identified and corrected. PMID- 8434436 TI - Electroejaculation. AB - Ejaculatory dysfunction is a relatively uncommon cause of male infertility. In men with total anejaculation and in some men with psychogenic anejaculation, electroejaculation is a very useful treatment. By following the guidelines provided, electroejaculation can be performed reproducibly and safely with a good success rate. Deviations from the safety techniques detailed may result in unsafe procedures. The risks involved with performing electroejaculation recklessly can be significant, including rectal injury and cerebrovascular accident from hypertension. Pregnancy rates from electroejaculation coupled with assisted reproductive techniques are not optimal, and much work continues at our center to determine why this is the case. PMID- 8434437 TI - Testis-sparing surgery for benign lesions of the prepubertal testis. AB - Testis tumors in children are more likely to be benign that those in adults, and those tumors that are malignant are associated with a much lower incidence of metastases. As a result, a less-aggressive surgical approach to pediatric lesions has evolved. A testis-sparing operation in appropriate cases has potential psychological and cosmetic advantages for the developing child, and there may be functional advantages for fertility when the child matures. PMID- 8434438 TI - Management of yolk sac tumors in children. AB - The current trend toward minimizing treatment morbidity in children with yolk sac carcinomas is laudable. As most children will present with stage I disease and be cured by radical orchiectomy alone, careful surveillance is adequate with the knowledge that effective chemotherapy is available should tumor recur. All new yolk sac carcinomas in children should be reported to the Prepubertal Testicular Tumor Registry and should ideally be treated at institutions that have experience with surveillance protocols and pediatric oncology. In this way, prospective studies on treatment options can be initiated, and management controversies may ultimately be ironed out. In particular, more information is needed on patients more than 2 years old, as the literature to date is contradictory regarding the prognosis for these patients and the need for adjuvant therapy when the older child presents with stage I disease. PMID- 8434439 TI - Surveillance in stage I seminoma of the testis. AB - In a health care system with adequate personnel and resources, careful surveillance, rigorously performed, following guidelines set out in the prospective trials is an appropriate alternative to adjuvant irradiation for patients with stage i seminoma of the testis. PMID- 8434440 TI - Variability in the embryotoxicity and fetotoxicity of vanadate with the day of exposure. AB - The aim of this study was to assess the variability in the developmental toxicity of vanadate with the day of administration during gestation. Single ip injections of 25 mg sodium metavanadata/kg were given to albino Swiss mice on one of the days 9-12 of gestation. Dams were killed on day 18 of pregnancy, and fetuses were examined for external, internal and skeletal malformations and variations. The number of dead or resorbed fetuses/litter, as well as the percentage of postimplantation loss, were significantly increased with injections on days 9-12 of gestation. However, the most sensitive time for the induction of metavanadate embryotoxicity was gestational day 12. Metavanadate treatment on day 12, but not days 9-11, resulted in a significant decrease in the fetal body weight/litter. There were no external, internal or skeletal malformations, whereas the most common skeletal variations were a reduced ossification in the parietal bone, metatarsals and metacarpals, bipartite sternebrae and fused ribs. The highest percentage of total skeletal defects was found on day 12 (82.3%). Gestational day 12 is the most sensitive time for metavanadate-induced developmental toxicity in mice. PMID- 8434441 TI - Studies on the acute lethality of diethylcarbamazine in the rat. AB - In spite of its effectiveness against microfilariae, very little is known about diethylcarbamazine's (DEC) therapeutic mechanism of action or the toxic sequelae which can result from overdose. In preliminary studies, a precipitous decrease in heart rate was noted in rats receiving 1000 mg DEC/kg ip. This effect was less pronounced at 750 mg/kg and was non-existent at 500 mg/kg. In the present study, attempts to attenuate DEC's cardiopulmonary insult by pretreating animals with cyproheptadine failed. Atropine pretreatment failed to block the negative chronotropic effects of DEC, but did restore respiratory function and reduce the lethality associated with the drug. Biochemical studies showed that ATP:ADP ratios in the hearts from rats given high dosages of DEC were elevated over those in controls (11:1 versus 5:1). Inosine levels decreased in cardiac tissues taken from DEC-treated rats. Subsequent enzyme studies revealed that DEC has a potent inhibitory effect on calcium-dependent ATPases from a variety of tissues. Taken together, our data indicate that the mode of acute DEC-lethality involves cardiopulmonary suppression. Furthermore, the cardiac depressant effect of DEC appears related to inhibition of calcium ATPases in cardiac myocytes. To our knowledge, this is the first report of ATPase sensitivity to DEC, a finding that has interesting toxicologic and pharmacologic ramifications. PMID- 8434442 TI - Resistance of ruminal microorganisms to supermethrin. AB - The effect of the pyrethroid insecticide supermethrin on the growth and cyanogenic activity of 8 ruminal bacterial species (S bovis A0 24/85, S xylosus 310, E faecium 2, L plantarum, M elsdenii 4MJ, S ruminantium A17, B succinogenes 16J and B ruminicola 3/3) in pure culture was examined. Bacteria grown in 0.66 and 6.6 mg supermethrin/ml had similar growth rates and resistance to supermethrin. Production of cyanide from supermethrin occurred by all examined strains of ruminal bacteria, but the enzyme activity varied considerably with species and with the supermethrin concentrations. PMID- 8434443 TI - Effect of CNS depressant drugs on acute intoxication from Palicourea marcgravii St Hill in rats. AB - Palicourea marcgravii (Pm) is a highly toxic plant to cattle in Brazil. Previous experiments showed that Pm intoxication in rats is similar to that reported for cattle. The present study was undertaken to determine if central nervous system depressant drugs protected animals against Pm-induced seizures. Doses of 30.0 mg diazepan/kg or 2.5 or 5.0 mg xyalzine/kg increased the ET50 for seizures. Only 4.0 mg chloral hydrate/kg + 10.0 mg xylazine/kg protected animals from death. Rats treated with sodium pentobarbital, diazepan or chlorpromazine died in depression after acute Pm intoxication. The combination of 2.0 choral hydrate/kg + 10.0 mg xylazine/kg protected rats against the Pm toxic effect, since all treated animal survived. PMID- 8434444 TI - The effects of malathion on some hormone levels and tissues secreting these hormones in rats. AB - Two dosage levels of malathion (10 and 100 mg/kg) were given po to albino rats daily for 15 w. The effects of malathion on T3, T4, aldosterone, cortisol, testosterone, estradiol 17-beta, and on the tissues secreting these hormones were investigated. Analysis of T3, T4, testosterone and estradiol 17-beta showed no difference in response while 10 mg aldosterone/kg showed a decrease. Serum cortisol also decreased in the same rats. Ovaries and thyroid glands in all groups had no histopathological changes, but slight changes were present in testes and adrenal glands of the dosed rats. PMID- 8434445 TI - Clinical evaluation of the effects of direct hemoperfusion on amino acid profiles. AB - We observed significant changes in serial aminograms during direct hemoperfusion (DHP) in clinical cases and decided to evaluate the effects of the procedure on amino acid profiles. DHP at 100 ml/min was carried out for 6 h in patients with drug intoxications. Pre- and post-column aminograms were obtained 0.5, 1, 2, 3, 4, 5 and 6 h from the beginning of DHP. Nonmolecular-weight-dependent adsorption of some amino acids to the column was observed. Methionine (MET), isoleucine (ILE), leucine (LEU), tyrosine (TYR), phenylalanine (PHE) and arginine (ARG) had high adsorption rates. Blood concentrations of TRY, PHE, TRY and histidine (HIS) were significantly reduced. Although both branched-chain amino acids (BCAA) and aromatic amino acids (AAA) were initially adsorbed by the column, AAA recovery was slow. PMID- 8434446 TI - Does intake of highly demineralized water damage the rat gastrointestinal tract? AB - Highly demineralized water (hd-water) is used frequently in laboratories and on an industrial scale. However, no systematic data seem available as to whether hd water has a toxic potential beyond the physical risks of drinking water (drowning, water intoxication). This study investigated the impact of hd-water on function and morphology of the rat's gastrointestinal tract. One group of rats received hd-water together with the usual diet ad libitum for 14 d. A second group was exposed to hd-water after withdrawal of food and water for 24 h. Both experiments had control groups which were treated identically except that hd water was replaced by tap water. Histology showed no signs of erosion, ulceration or inflammation in the esophagus, stomach or jejunum. Body weights and the uptake of food and water were not significantly different between the hd-water exposures and controls for 14 d. Tissue alkaline phosphatase activity was unaltered, and the mitotic rate in the epithelium of the esophagus and stomach were not different between controls and rats on hd-water. Exposure to hd-water caused no changes in the km or Vmax values for the uptake o of alpha-methyl-D-glucose from the upper jejunum. There findings indicate no impact of hd-water on the function or morphology of the rat gastrointestinal tract. There is no need for additional safety regulations when working with hd-water which go beyond those considered adequate to prevent drowning and water intoxication. PMID- 8434447 TI - Conservative treatment of jimsonweed ingestion. AB - The use of physostigmine for the treatment of jimsonweed ingestion remains controversial. We have reviewed the records of 29 cases reported to the Kentucky Regional Poison Center (KRPC) over a 7-y period during which time physostigmine was not recommended by the Center to assess the results of conservative therapy. 28/29 cases represented intentional abuse; 26/29 were males and the mean age for the group was 18.9 y (range 16 mo to 39 y). The reported ingested amounts ranged from a few to 1/2-cup of seeds. Typical mild anticholinergic symptoms including mydriasis, tachycardia, flushing, hallucinations, and both agitated behavior and lethargy were observed. No patient had life-threatening symptoms. All cases were referred to the Emergency Department, although only 20 complied. Of these, 17 were admitted for stays of 1-3 d (mean 1.8). Seventeen patients received activated charcoal on recommendation of the KRPC. Three patients with hallucinations received 1 or more doses of valium or haloperidol for sedation. All patients recovered uneventfully. We conclude that conservative treatment of jimsonweed ingestion is safe and adequate. PMID- 8434448 TI - Accidental chronic salicylate intoxication in an elderly patient: major morbidity despite early recognition. AB - Chronic salicylate intoxication represents an unappreciated form of self poisoning in the elderly and therefore poses a diagnostic challenge. This report describes an elderly female with chronic salicylism who presented with unexplained delirium, dysarthria, diminished short-term memory and hearing, and urinary and fecal incontinence. She was treated with intravenous hydration, urinary alkalinization, and subsequent hemodialysis for persistent aciduria, acidemia and impending circulatory collapse. Major morbidity included myocardial infarction, life-threatening dysrhythmias, and mixed bacterial urosepsis. This report highlights the need to maintain a high index of suspicion for salicylate poisoning in the elderly, who commonly present with nonfocal neurologic features. PMID- 8434449 TI - Effectiveness of morphine in non-cardiogenic pulmonary edema due to chlorine gas inhalation. AB - We report the case of an 11-yr-old boy who developed a non-cardiogenic pulmonary edema following inhalation of chlorine gas at a swimming pool. Rapid clinical improvement was noted after i.v. administration of morphine. PMID- 8434450 TI - A hazardous material episode: sulfur trioxide. AB - Twelve people working next to a chemical plant noted an emission of 2 h. Nine patients complained of a variety of symptoms, including 3 who had pleuritic chest pain, 2 with chest tightness, 2 with vague chest discomfort, 3 with eye irritation, 2 with dizziness, 1 with light-headedness, 1 with cough and 1 with an acidic taste in the mouth associated with nasal irritation. Pulmonary function was 100% of predicted in 5; 77.4, 85.7, 95.7, and 96.7% of predicted in the other 4. Three of the 4 with initial decreased FEV1's (forced expiratory volume in 1 sec) improved. At follow-up, 1 had burning sensation of the tongue and mouth; a second noted burning sensation of his throat, tip of his tongue, and nostrils; and a third had superficial exfoliative-type lesions at the junction of her forehead and scalp. Two complained of continuous pleuritic chest pain. Sulfur trioxide exposure caused self-limited irritant effects. PMID- 8434451 TI - Hoary alyssum (Berteroa incana) toxicity in a herd of broodmare horses. AB - A herd of pregnant horses exposed to hoary alyssum through ingested hay developed acute and severe gastrointestinal toxicity accompanied by intravascular hemolysis. Postmortem lesions were consistent with these signs. Three horses had late-term abortions. PMID- 8434452 TI - Age-related effects in the inhibition of oxidative metabolism of xenobiotics by mancozeb. AB - The effect of po administration of 100 or 200 mg mancozeb/kg body weight for 7 consecutive days on microsomal mixed-function oxidase catalyzed xenobiotic metabolism was investigated in the livers of newborn weanling and adults rats. Mancozeb caused a dose-dependent inhibition in the activities of p-nitroanisole O dealkylase and aniline hydroxylase, while the activities of aminopyrine N demethylase and benzo(a)pyrene hydroxylase were unaffected in all the age groups. The inhibition of p-nitroanisole O-dealkylase and aniline hydroxylase, was remarkably higher in adult than in newborn and weanling rats. There was a concentration-dependent decrease in cytochrome P-450 and microsomal protein contents. This study indicates selective age-independent inhibition of hepatic monooxygenases following repeated mancozeb dosing. PMID- 8434453 TI - Pipazethate lethality in a baby. PMID- 8434454 TI - Outcome productivity assessment: using random alarm devices. PMID- 8434455 TI - PC2: using electronic mail in a poison center. PMID- 8434456 TI - Liver cirrhosis in rheumatoid arthritis patients treated with long-term methotrexate. AB - We undertook a retrospective review of all the liver biopsies done by us between 1985 and 1990 for the purpose of monitoring methotrexate (MTX)-induced hepatotoxicity in rheumatoid arthritis (RA) patients. A total of 29 biopsies were done in 25 patients. The mean total cumulative dose of MTX was 1585 +/- 348 (SD) mg. Average duration of MTX therapy was 31 +/- 9.8 mo (SD). Liver biopsy after accumulating 900 mg and 1200 mg MTX, respectively, in 2 obese diabetic patients showed evidence of cirrhosis. Obese diabetics may represent a subgroup of RA patients at risk for developing MTX-induced hepatotoxicity. PMID- 8434457 TI - Intoxication by Senecio tweediei in cattle in southern Brazil. PMID- 8434458 TI - A fierce fire in a railroad yard on a bitter cold night shows the need for TOXNET information. PMID- 8434459 TI - Allelochemicals in plant foods and feedingstuffs: 1. Nutritional, biochemical and physiopathological aspects in animal production. AB - Several allelochemicals (anti-nutritional/anti-quality factors) contained in some plant foods and feedingstuffs are outlined. These include the trypsin and amylase inhibitors, hemagglutinins, gossypol, cyanogenic glycosides, tannins, oxalates, phytin, saponins, glucosinolates, estrogens, coumarins, alkaloids and aflatoxins. The nutritional, biochemical and physiopathological implications of their ingestion in a wide range of animals are reviewed. These include impaired growth, feed consumption, efficiency of feed utilization, alterations of normal enzyme activities, organ atrophy, necrotic changes, lesions and changes in normal hematological indices. The induction of increased dietary requirements for such nutrients as methionine, lysine, vitamins and divalent ions (eg Fe, Ca, Mg and Zn) by some of these factors is discussed. Ameliorative measures aimed at minimizing the concentrations and anti-nutritional effects of these factors are processing and including additives in the diet, or genetic manipulations. There is a need to prevent both functional and nutritional damage of food proteins and other nutrients arising from excessive heat treatment. PMID- 8434460 TI - Effect of malathion, estradiol-17-beta and progesterone on ascorbic acid metabolism in prenatal rats and their pups. AB - The effects of prenatal exposure to 13.78 mg, 27.56 mg or 82.6 mg malathion/100 g body weight po from 6-13 d of gestation, to 1 microgram estradiol-17-beta/d/100g body weight or 4 mg progesterone/d/100 g body weight sc from 3-20 d of gestation, or to their various combinations on brain acetylcholinesterase activity and ascorbic acid metabolism were investigated in rat dams and pups. Brain acetylcholinesterase activity was taken as an index of toxicity. Significant inhibition of acetylcholinesterase from malathion exposure was further exaggerated by estradiol-17-beta, but was reversed by progesterone. Significant increases of ascorbic acid levels and L-gulonolactone oxidase was observed with malathion toxicity. Estradiol-17-beta decreased ascorbic acid levels and stimulated dehydroascorbatase, while progesterone had no significant effect on ascorbic acid levels or on enzyme activities. PMID- 8434461 TI - Health risks of "dioxins": a review of environmental and toxicological considerations. AB - Polychlorinated dibenzo-p-dioxins are the focus of great public concern because of the extreme toxicity of some congeners in animal studies, their apparent ubiquity in our food and the environment, and their involvement in some well publicized environmental contamination incidents. This review summarizes and discusses some environmental and toxicological aspects of dioxins, with major focus on the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). In many animals, 2,3,7,8-TCDD is extremely toxic, but species differences are evident. Humans appear more resistant to the effects of 2,3,7,8-TCDD than most animal species tested. However, since human exposure has usually occurred to a mixture of chemicals, of which 2,3,7,8-TCDD is only 1 component, it is often difficult to clearly relate effects in humans to exposure to this compound. So far, it appears that chloracne is the only proven consequence of human exposure to 2,3,7,8-TCDD. Attempts to estimate the carcinogenic risk from 2,3,7,8-TCDD in humans have failed to provide reliable evidence. However, the International Agency for Research on Cancer has classified this compound as a possible human carcinogen based on animal studies. Whether 2,3,7,8-TCDD, in small quantities, poses any significant health risk is still debatable. It appears prudent to limit human exposure to this compound as much as possible. PMID- 8434462 TI - Immediate health effects of an urban wildfire. AB - To document the immediate health effects of the urban wildfire that swept through parts of Alameda County, California, on October 20 and 21, 1991, we conducted a retrospective review of emergency department and coroner's records. Nine hospitals (6 local and 3 outlying) were surveyed for the week beginning October 20, 1991. Coroner's reports were reviewed for 25 identified fire-related deaths. A total of 241 fire-related emergency encounters, including 44 inpatient admissions, were recorded for 227 persons. Nearly a fourth of emergency department patients were seen for work-related injuries, more than half of which occurred among professional firefighters. Smoke-related disorders constituted more than half of all emergency department cases; of these, 61% had documented bronchospasm. Major trauma and burns contributed 1% and 4% of principal diagnoses, respectively; these were exceeded in number by corneal abrasions (13%), other medical problems (8%), and minor trauma (7%), among other diagnoses. All coroner's cases involved extensive burns, many with documented smoke inhalation injury. While the Oakland-Berkeley fire storm resulted in a high case fatality ratio among major burn cases (25/31), those who survived the initial fire storm did well clinically. Among emergency department patients, medical (particularly smoke-related) disorders outnumbered traumatic presentations by a ratio of more than 2 to 1. PMID- 8434463 TI - Black spots on the scalps of schoolchildren. A recurrent condition in the windy west. AB - During the past 10 years, epidemics of black spots on the scalps of schoolchildren have caused considerable concern in at least 4 communities in the Rocky Mountain states. We describe the clinical presentation of "black spots" in a group of Wyoming elementary school students and the epidemiologic investigation that revealed the cause. Our study included a questionnaire survey of students' parents, examination of students at the affected school and at two other schools, observation of playground activity patterns, and laboratory analysis of specimens taken from affected children and from the school environment. The black material in the scalp spots was chemically identical to flakes of black material found on the playground and tar from the school roof. We concluded that the spots were caused by flakes of windblown tar from the school roof. Previous outbreaks of black spots may have had a similar cause. PMID- 8434464 TI - Physicians' adjustment to retirement. AB - We address the questions, How do physicians adjust to and enjoy their retirement? What factors contribute to the well-being of retired physicians? A 60-item questionnaire mailed to 238 retired physicians in Los Angeles County with a 41.6% response rate assessed health, standard of living, relationships, activities, emotional difficulties, and general enjoyment. Health often improved after retirement, as did relationships with spouses and children. Standard of living was comfortable or better for most. Retired physicians engage in a wide range of interests and activities. Emotional difficulties are minimal and considerably reduced after retirement. Most physicians enjoy the freedom and activities of retirement and are happy. Fears of boredom and deterioration are unfounded. PMID- 8434465 TI - Prevalence of human immunodeficiency virus infection in a sample of immigrants in the United States. AB - EDITOR'S NOTE: Years ago, experts predicted that the acquired immunodeficiency syndrome would spread to every part of the world and every part of society. The articles by Studemeister and Kent and Calonge and co-workers(*) that follow are further evidence that this is happening. These and other articles we will publish in the next few months confirm our worst fears and challenge all of us to continue engaging in basic, applied, and behavioral research and to continue providing the very best care, ranging from prevention through hospice, with an emphasis on compassion. PMID- 8434466 TI - Human immunodeficiency virus seroprevalence in primary care practices in the United States. PMID- 8434467 TI - Blood coagulation and its alterations in hemorrhagic and thrombotic disorders. AB - Clinical observations have added to the understanding of basic mechanisms of blood coagulation and its alterations in certain hemorrhagic and thrombotic states. Much clinical evidence exists for concluding that the exposure of blood to tissue factor (thromboplastin) on tissue cells represents the key event initiating fibrin clot formation after tissue injury. This then results in the formation of activated factor VII (VIIa)-tissue factor complexes, which must activate both factor X and factor IX for normal hemostasis. I describe the possible clinical consequences of an aberrant function of the natural anticoagulants regulating blood coagulation--antithrombin, protein C, and tissue factor pathway inhibitor. Understanding the physiologic function of tissue factor pathway inhibitor can illuminate why hemophilic patients bleed, but many other questions remain. I briefly review the four causes for acquired disorders of the blood coagulation reactions--vitamin K deficiency, hepatocellular disease, antibodies to clotting factors, and disseminated intravascular coagulation--but limit my comments to the mechanisms that trigger the formation of antibodies to clotting factors and how these antibodies can deplete the blood of clotting factor activities. Finally, heparin is able to potentiate tissue factor pathway inhibitor function, which is a possible reason why the use of heparin but not warfarin can prevent the numerous thrombotic episodes of the Trousseau's syndrome. PMID- 8434469 TI - Lumbar spinal stenosis. AB - Lumbar spinal stenosis, the results of congenital and degenerative constriction of the neural canal and foramina leading to lumbosacral nerve root or cauda equina compression, is a common cause of disability in middle-aged and elderly patients. Advanced neuroradiologic imaging techniques have improved our ability to localize the site of nerve root entrapment in patients presenting with neurogenic claudication or painful radiculopathy. Although conservative medical management may be successful initially, surgical decompression by wide laminectomy or an intralaminar approach should be done in patients with serious or progressive pain or neurologic dysfunction. Because the early diagnosis and treatment of lumbar spinal stenosis may prevent intractable pain and the permanent neurologic sequelae of chronic nerve root entrapment, all physicians should be aware of the different neurologic presentations and the treatment options for patients with spinal stenosis. PMID- 8434470 TI - Recent advances in pediatric liver transplantation. AB - The Council on Scientific Affairs of the California Medical Association presents the following inventory of items of progress in pediatrics. Each item, in the judgement of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome, and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, and scholars to stay abreast of these items of progress in pediatrics that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another. The items of progress listed below were selected by the Advisory Panel to the Section on Pediatrics of the California Medical Association, and the summaries were prepared under its direction. PMID- 8434471 TI - Advances in the management of childhood asthma. PMID- 8434468 TI - Interventional neuroradiology. AB - A wide variety of diseases affecting the central nervous system and head and neck can be treated using interventional neuroradiologic techniques. These new treatments have depended on advances in radiologic imaging, catheter technology, and the development of new embolic agents. These procedures may be an adjunct to other therapy, palliative or curative. Diseases for which interventional neuroradiologic techniques have been major advances in treatment include cerebral aneurysms, vasospasm after subarachnoid hemorrhage, cerebral arteriovenous malformations, dural arteriovenous fistulas, dural sinus thrombosis, atherosclerosis, scalp arteriovenous fistulas, carotid-cavernous fistulas, and stroke. This field is rapidly evolving as advances are made in catheter technology and new embolic agents are developed. PMID- 8434472 TI - Human genome project. PMID- 8434473 TI - Sleep positioning and the sudden infant death syndrome. PMID- 8434474 TI - Management of intracranial and spinal cord vascular lesions in children. PMID- 8434475 TI - Laparoscopic surgery. PMID- 8434476 TI - Depot levonorgestrel (Norplant) use in teenagers. PMID- 8434477 TI - Successful combined liver and small intestine transplantation for short-gut syndrome and liver failure. PMID- 8434478 TI - Occult Kawasaki syndrome with giant coronary artery aneurysms. PMID- 8434479 TI - Anion and osmolal gaps in a patient with alcoholism. PMID- 8434480 TI - Why does the blood not coagulate? PMID- 8434481 TI - The final career. PMID- 8434482 TI - Endovascular neurosurgery--the marriage of imaging and intravascular therapy in the decade of the brain. PMID- 8434483 TI - Late relapse of tick-borne relapsing fever following treatment with doxycycline. PMID- 8434484 TI - Judaism and the belief in an afterlife. PMID- 8434485 TI - [Carcinoma and oncocytoma of the kidney. Phenotypic characteristics and prognostic features]. AB - The present investigation is based on the morphological analysis of 1224 renal cell carcinomas and 68 renal oncocytomas from the kidney tumor registry of the Institute of Pathology, University of Mainz. The subclassification of epithelial renal cell tumors in 5 basic types (i.e. clear cell type, chromophilic type, chromophobic type, oncocytic type and duct Bellini type) as proposed by Thoenes and coworkers (1986) was taken as the basis for a systematical study. It refers especially to ultrastructural aspects and antigen profiles of the tumor cells established immunohistologically in relation to the nephron/collecting duct epithelia. Thus, the study focuses on problems of phenotypia and histogenesis. Finally, morphological parameters of prognosis in renal cell carcinomas are taken into account as well. I. Ultrastructural analysis provides further knowledge of the morphological differences between the various basic cell types of epithelial renal tumors. Structural similarities are presented between the basic cell types of clear cell and chromophilic renal cell carcinomas and cells of the proximal tubules, on the one hand, and the basic cell types of the chromophobic renal cell carcinomas, duct Bellini carcinomas as well as oncocytomas and cells of the collecting duct, on the other hand. This can sometimes be traced back to the single cell level (chromophobic renal cell carcinomas: intercalated cell type B). The results of the freeze fracture analysis confirm this view and, for the first time, morphologically prove molecular anomalies of the oncocytic mitochondria membrane. Initial tumor development can be observed for the chromophilic renal cell carcinoma, the duct Bellini carcinoma, as well as the renal oncocytoma and chromophobic renal cell carcinoma. This development demonstrates the relationship these tumor types have to well-defined segments of the nephron/collecting duct (i.e. proximal tubule, medullary and cortical collecting duct). II. The immunohistological analysis demonstrates characteristic antigen profiles of every renal tubule segment and of every epithelial renal tumor type which can be used for differential diagnosis purposes. Two tumor groups with different morphological phenotypes can be identified. The first group (clear cell and chromophilic renal cell carcinomas) mostly presents antigens of the proximal tubule, while the second group (chromophobic renal cell carcinomas, duct Bellini carcinomas, oncocytomas) mostly expresses antigens of the collecting duct. In the case of the renal oncocytomas, for example, the expression of the band 3 antigen exhibits a relationship to the single cell level (i.e. the intercalated cells type A).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8434486 TI - Imprint cytology of needle-localized breast lesions. AB - Intraoperative evaluation of nonpalpable breast lesions by frozen section frequently is not performed because of potential tissue loss, sampling errors and frozen section artifacts. In a retrospective review we found that only 50 of 503 needle-localized breast biopsies (NLBBs) were evaluated at our institution by frozen section (FS), with a sensitivity of 88%. However, intraoperative evaluation of such lesions may be essential to single-stage and cost-effective management. To this end, this study evaluated the diagnostic accuracy and potential clinical role of intraoperative imprint cytology (IIC) in NLBB. A total of 88 lesions were evaluated by IIC and permanent histology. Fifteen of them were also concomitantly evaluated by FS. All but one deferred cytologic diagnoses were correct. Twelve of 15 FS diagnoses were correct, 2 were deferred, and 1 was false negative. The data suggest that IIC may circumvent some of the difficulties associated with FS, thereby allowing immediate clinical management and later definitive histologic typing and evaluation of prognostic parameters in nonpalpable breast lesions. PMID- 8434487 TI - Fine needle aspiration cytology of cervicofacial actinomycosis. PMID- 8434488 TI - Method of smear preparation in intraoperative cytology. PMID- 8434489 TI - Oncocytic tumor of the pancreas. PMID- 8434490 TI - Causes of false results in transthoracic fine needle lung aspirates. AB - To evaluate the causes of false-negative and false-positive results in transthoracic fine needle aspirates (TFNAs), we reviewed our experience with this technique over the 20-year period from 1972 to 1991. For 488 TFNAs satisfactory for cytologic interpretation, tissue diagnoses were subsequently obtained by biopsy, resection or autopsy in 218 cases (56 benign and 162 malignant). In 11 cases, TFNA was positive for malignancy, and the biopsy was negative. Review of these cases disclosed that the TFNAs were true positives (specificity, 100%) and that the biopsies failed to sample the lesion. There were 18 false-negative results by TFNA, for a sensitivity of 90%, all as a result of failure to sample the lesion. TFNA is a highly specific and sensitive technique for diagnosis of benign and malignant lung masses. False negatives are the result of failure to sample the lesion. False positives are uncommon but can be avoided if the cytopathologist is aware that benign reactive lesions may mimic malignancy on cytology. PMID- 8434491 TI - Detection of pulmonary neoplasms by bronchial washings. Are cell blocks a diagnostic aid? AB - While cell blocks of bronchial washings are often routinely prepared, their usefulness as adjuncts to the diagnosis of pulmonary neoplasms has not been evaluated. Bronchial washings obtained from 111 patients in whom clinical or radiographic evidence raised the suspicion of a pulmonary neoplasm were reviewed. The smears and cell block preparations were studied independently of each other without knowledge of the original diagnoses. Discrepancies between the smear and cell block diagnoses were noted in 17 cases. Smears detected more neoplasms (52) than cell blocks (43). However, four cell blocks were positive, while the corresponding smears were negative. According to these results, the use of cell blocks increased the diagnostic yield from 52 to 56 cases, for an increase of 9%. Cell blocks will increase the diagnostic yield of bronchial washings, albeit for a small number of patients. However, a positive result will have an obvious influence on patient management and will obviate incremental costs and risks attendant to more invasive diagnostic procedures. PMID- 8434492 TI - Comparison of different preparation techniques for fine needle aspiration specimens. A semiquantitative and statistical analysis. AB - Different options exist for preparing fine needle aspiration specimens (FNAS). To compare direct smears and cytocentrifugation specimens, we prospectively obtained FNAS from 38 operative cases, making alcohol-fixed (DIR) and air-dried (AIR) direct smears and collecting additional passes in 50% ethanol (ETH), Saccomanno's solution (SAC) and Hanks' Balanced Salt Solution (HBSS). All slides were stained with Papanicolaou stain except AIR, which were stained with Diff-Quik. We evaluated cellularity, nuclear and cytoplasmic preservation, percent single cells, background and degree of three-dimensionality on a 0-3+ scale and rendered an independent diagnosis for each medium. Statistical analysis of differences between techniques was performed utilizing the paired t test. Cellularity was significantly decreased for ETH, HBSS and SAC as compared to DIFF and DIR. Nuclear preservation was best for DIR and inferior for AIR, ETH, SAC and HBSS. Background was best seen in DIR and AIR as compared to ETH and SAC. HBSS was significantly inferior to DIR but not to AIR. There were no significant differences in cytoplasmic preservation and percent single cells. Three dimensionality was increased for ETH and SAC but not for HBSS. The ability to make a definitive diagnosis was significantly inferior only for HBSS and SAC as compared to AIR. Direct smears made by cytotechnologists or pathologists are better than Cytospin specimens. However, despite their inherent disadvantages, rinse techniques may be advantageous when specimens are collected solely by clinicians. PMID- 8434493 TI - A new syringe for fine needle aspiration biopsy. AB - In order to improve the technique of fine needle aspiration biopsy (FNAB), we developed a disposable syringe that allows one to perform aspiration with one hand while eliminating the need for a classic syringe holder. This study compared the cellularity and diagnostic adequacy of the material obtained with the new syringe and a syringe holder. Moreover, the acceptance of the new technique by physicians in training and by patients was tested. FNAB was performed with a syringe holder and the new syringe on 120 lesions from different body sites. The total number of diagnostic cells and their relative percentage were estimated. The results of the study indicated that the adequacy of a conclusive cytologic diagnosis was similar for both techniques. Moreover, a comparable cellular yield was demonstrated by a linear relationship between the total number of diagnostic cells (r = .84, slope = .83). The new technique was favorably accepted by physicians in training and patients. FNAB with the new syringe can be performed routinely. PMID- 8434494 TI - Smear technique for the intraoperative examination of nervous system lesions. AB - To evaluate the accuracy of the smear technique in the rapid diagnosis of lesions of the central and peripheral nervous system, intraoperative diagnoses made on cytologic preparations in 307 consecutive cases were compared with the final paraffin section diagnoses. In 92.2% of cases the final diagnosis obtained on paraffin preparations was similar to that made on smears. In this group there were neuroglial tumors, meningiomas and medulloblastomas, among others. In the cases in which the cytologic diagnoses were not confirmed by paraffin sections, the majority of the cases were unlikely to affect immediate neurosurgical management, while in only 0.7% of all cases (n = 2) an incorrect smear diagnosis might have affected the neurosurgical procedure. The cytologic diagnostic criteria are discussed together with the main difficulties in interpretation with this valuable approach to a rapid neurosurgical diagnosis. PMID- 8434495 TI - Confocal sectioning of thick, otherwise undiagnosable cell groupings in cervical smears. AB - Confocal sectioning of thick, otherwise undiagnosable cell groupings in cervical smears results in detailed visualization of the diagnostic features of neoplastic fragments in the original Cytobrush smear. We argue that the large step forward due to confocal microscopy is the dramatic improvement of axial resolution, resulting in images with a high degree of detail. As a result, mitotic figures, chromatin patterns and glandular spaces materialize out of the blur. When the serial confocal sections are compared to the parallel thin, plastic sections, some differences in the images are observed mainly due to the absence of infiltration by plastic. This study showed that the confocal microscope can be very useful in the diagnostic laboratory because the information extracted from a sample containing these otherwise undiagnosable cell groupings is enhanced to such a degree that a final diagnosis can be made with confidence, maximizing the benefit of the sampling and thus increasing its value. PMID- 8434496 TI - Intralaboratory reproducibility in cervical cytology. Results of the application of a 100-slide set. AB - In order to evaluate the agreement and accuracy of cervical (vaginal) cytologic diagnoses, 16 cytologists from a large laboratory in Florence, Italy, with experience ranging from 2 to 25 years, independently examined a set of 100 slides. A common reporting form based on a seven-category classification system was used. Concordance was calculated for each pairwise comparison between the 16 cytologists and between each cytologist and the target diagnosis. The values of the kappa statistic for the whole laboratory were .49 for the multiple raters comparison and .59 for the target diagnosis comparison, showing a relatively good degree of agreement. PMID- 8434497 TI - The Bethesda System. Impact on reporting cervicovaginal specimens and reproducibility of criteria for assessing endocervical sampling. AB - This study examined the impact of applying the Bethesda System guidelines for specimen adequacy on cytopathologic diagnosis at the Johns Hopkins Hospital laboratory of cytopathology during a one-year period. Application of the Bethesda guidelines resulted in a 1.3% unsatisfactory rate. In addition, 3.8% of specimens were satisfactory but contained an inadequate endocervical component (IEC). Smears obtained after a cone biopsy or an initial IEC smear were IEC in 16.5% and 18.7% of cases, respectively. The IEC rate following an initial smear lacking an endocervical component was 11.8% in repeat specimens obtained with an endocervical brush as compared to 29.4% in those obtained with a spatula alone. The reproducibility of the Bethesda criteria for assessing endocervical sampling was evaluated by comparing the level of agreement between three independent reviewers examining 40 test cases. Three-way agreement was achieved in 75% of cases. Two-way agreement ranged from 80.0% to 87.5%. We conclude that implementation of the Bethesda System guidelines for assessing specimen adequacy should produce a minimal impact on cytopathologic reporting and gynecologic practice. Repeat specimens lacking an endocervical component may be encountered relatively frequently in certain subsets of patients. PMID- 8434498 TI - Fine needle aspiration of the testis and correlation with testicular open biopsy. AB - The diagnostic value of cytologic examination of aspiration biopsy smears was compared with that of histologic examination of surgically removed biopsy specimens from 54 testes in 32 men with oligoazoospermia. In 47 testes (87.1%) a good correlation was found between the results of the two methods: 20 cases had normal testicular morphology, 10 cases had spermatogenic arrest, and 17 had only Sertoli cells. In the remaining seven cases there was a paucity of cells, not permitting a cytologic diagnosis. FNA of the testis is a reliable and simple method of evaluating male infertility. PMID- 8434499 TI - Fine needle aspiration cytology of the spleen in visceral leishmaniasis. AB - We describe the fine needle aspiration cytologic study of 210 splenic aspirates from patients clinically diagnosed as having visceral leishmaniasis. Of these, 147 aspirates were found to be positive for Leishmania donovani bodies. We highlighted the cytomorphology of these positive smears. A majority of the cases showed an increase in the number and size of reticuloendothelial cells, with altered shapes, variations in the cytoplasm and decreased white pulp elements. In some of these cases (10%), immature erythroid cells were also found. PMID- 8434500 TI - Aspiration biopsy cytology of primary bone lesions. AB - Fine needle aspiration cytology of 79 primary bone lesions was done, and the clinical and radiologic features were correlated with cytopathology. Seventy-four of these cases were primary malignant bone tumors, two cases each were tumor-like or inflammatory lesions, and one case was a benign bone tumor. Osteosarcoma (37.7%) and Ewing's sarcoma (15.6%) were the most common primary lesions. Correlation with histopathology was possible in 37 cases, and an accuracy rate of 94.1% was achieved. There was an 89% correlation between radiologic and cytologic diagnoses. It was concluded that in this oncology center a working diagnosis based on cytology was possible in almost all cases after correlating with the radiologic findings. However, when there was a discrepancy between the clinical, radiologic and cytologic diagnoses, an open biopsy was mandatory. PMID- 8434501 TI - Reed-Sternberg cells in sputum from a patient with Hodgkin's disease. A case report. AB - A patient with stage IV Hodgkin's disease developed severe dyspnea and was found to have pulmonary infiltrates one year following his initial diagnosis of nodular sclerosing Hodgkin's disease, stage IIB. Two separate cell block sputum cytology samples demonstrated Reed-Sternberg cells. The patient died of respiratory failure. At autopsy the main findings were extensive confluent nodules of Hodgkin's disease nearly replacing the pulmonary parenchyma of both lungs. Cytology of sputum or bronchial washings may reveal diagnostic Reed-Sternberg cells and establish the diagnosis of pulmonary Hodgkin's disease without a lung biopsy. PMID- 8434502 TI - Morphological evidence for a cecocolonic junction in man and functional implications. AB - The region above, below and in front of the ileocecal valve opening has been studied in man using both light and electron microscopy. A cecocolonic junction, comprising the colonic basal portion of the ileocecal valve, could be demonstrated in man, due to the specific anatomy of the inner portion of the circular muscle. This muscle was arranged in anastomosing cords, richly innervated and enveloped by elastic fibers. Its smooth muscle cells were characterized by extremely wide sarcoplasmic cisternae and cell-to-cell junctions, numerous caveolae and large amounts of glycogen. Interstitial cells were rarely found. This junction might be considered responsible for (1) ileal flow accommodation, (2) colonic active movements and (3) ileocecal valve closing and opening. PMID- 8434503 TI - Distribution of extracellular matrix components during early embryonic development in the macaque. AB - The distribution of fibronectin (FN), laminin (LM), hyaluronic acid (HA) and chondroitin sulfate (CS) were examined by peroxidase immunocytochemistry in long tailed monkey embryos during the period of neural tube and notochord formation (stages 8-11). Reactivity for each component in the neuroepithelial basement membrane (BM) increased with advancing development. Discontinuous staining was observed in areas of epithelial-to-mesenchymal transformation, i.e. in dorsolateral sites of neural crest emigration and in the axial region of the primitive streak. The BM forming around the developing notochord also showed increased reactivity for FN, LM, HA and CS between stages 8 and 11. No staining occurred within the notochord. Stage-related increases in reactivity in the mesenchymal matrix was particularly notable for FN and HA which were ubiquitous throughout the mesoderm by stage 11. The results of this study are consistent with the proposed role of these components in maintaining epithelial integrity and providing a permissive substrate for cell migration during development. The observed temporal and regional staining patterns suggest that these glycoproteins and glycosaminoglycans are important morphogenetic factors in the macaque. PMID- 8434504 TI - Innervation of the human adrenal cortex: simultaneous visualisation using acetylcholinesterase histochemistry and dopamine beta-hydroxylase immunohistochemistry. AB - The inter-relationship between putative cholinergic and noradrenergic innervation of the human adrenal cortex was investigated using a technique which combined acetylcholinesterase histochemistry, choline acetyltransferase radiochemistry and dopamine beta-hydroxylase immunohistochemistry. Cholinergic and noradrenergic nerve fibres had a near-identical distribution, with varicose noradrenergic fibres located immediately alongside non-varicose cholinergic nerve bundles in all cortical zones. Choline acetyltransferase activity was consistently detected in the adrenal cortex, confirming the presence of cholinergic neurons. It is postulated that noradrenergic innervation has a role in the modulation of cortical endocrine secretion, while cholinergic nerves are mainly concerned with the control of medullary secretion. PMID- 8434505 TI - The sensory innervation of the gingiva and mucosa in Monodelphis domestica: an ultrastructural study. AB - The location and structure of sensory nerve endings was examined in the mucosa and in the gingiva propria adjacent to the third premolar of Monodelphis domestica by light and electron microscopy. The mucous membrane of the gingiva propria is covered with a stratified keratinized squamous epithelium. The mucous membrane of the adjacent inner aspect of the lip and of the vestibulum oris were covered with a nonkeratinized squamous epithelium. Free nerve endings, Merkel nerve endings and lamellated corpuscles were found in all the examined areas. Free nerve endings were located in the connective tissue papillae between the epithelial cones, in the basal layer of the epithelium and directly under the epithelium of the cones. They were innervated by myelinated A-delta- and nonmyelinated C-fibers. The basal layer of the first three to four epithelial cones of the gingiva propria contained single or groups of Merkel nerve endings. The epithelial cones of the oral mucous membrane contained five times more Merkel nerve endings than those of the vestibular mucous membrane. Lamellated corpuscles were mainly found in the plica sublingualis. In the connective tissue below the epithelial cones of the mucous membranes they usually occur with a perineural capsule, in the connective tissue papillae between the cones they occur without a perineural capsule. In the latter position they resemble the Meissner corpuscles of glabrous skin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8434506 TI - The sensory innervation of the periodontium of the third premolar in Monodelphis domestica. AB - Location and structure of sensory nerve endings in the periodontium of the third premolar in Monodelphis domestica have been investigated by means of light and electron microscopy. The periodontal cleft of the tooth is apically enlarged. The number of nerve endings increases towards apex. Three types of sensory nerve endings have been observed: free nerve endings, Ruffini nerve endings and lamellated corpuscles. Free nerve endings could only be identified by electron microscopy. Ruffini nerve endings are only incompletely surrounded by lamellae of the terminal Schwann cell. Protrusions of nerve terminals of the Ruffini corpuscles are anchored between bundles of collagen fibers. Small lamellated corpuscles occur exclusively in the apical portion of the periodontium. Ruffini and lamellated corpuscles are considered as part of a masticatory reflex feedback control system. Ruffini corpuscles detect tension, rapidly adapting lamellated corpuscles detect pressure and vibration in the periodontium. Free nerve endings may function as thermoreceptor or nociceptor. PMID- 8434507 TI - Accessory oculomotor nuclei of man. III. The nuclear complex of the posterior commissure: a Nissl and Golgi study. AB - A morphoquantitative study was carried out to clarify the cytoarchitecture of the human nuclear complex of the posterior commissure (NPC), a collection of cell groups which is thought to be involved in the pupillary light reflex and eye movements. On the basis of the topographical features, 5 different parts (rostral, principal, magnocellular, subcommissural and infracommissural) were identified in NPC. In these 5 parts, the neuronal population consisted of small and medium-sized neurons with a structural pattern similar to that of the central reticular formation. The only exception was the magnocellular part in which the neurons, mainly medium-sized and large, did not show the reticular-like features. In the Golgi material, two types of NPC neurons were identified: multipolar and fusiform cells. In the multipolar cells, 2-3 dendrites emerged from the soma and gave off a wide dendritic arborization. Many of the dendrites and axons of the multipolar cells were seen spreading outside NPC. The fusiform cells had 2 dendrites emerging from the opposite poles of their elongated perikaryon. Dendrites and axons of the fusiform cells always lay inside NPC. These observations suggest that the multipolar cells are mainly projective neurons and that the fusiform cells are neurons which mainly perform a local integrative function. Since the present study concludes our investigation of the human accessory oculomotor nuclei, a comparison of their structure was carried out. All the nuclei showed a common reticular-like structure, although each nucleus had its own structural particularities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8434508 TI - Ramification of the intercostal nerves in the rhesus monkey (Macaca mulatta) with special reference to the innervation of the intercostal muscles. AB - Detailed dissection was performed on the ventral primary rami from the first thoracic to the second lumbar nerves in order to obtain more comprehensive data of the ramification of the intercostal nerves in the rhesus monkey. The nerves to the intercostalis intimus and internus and the obliquus externus abdominis tended to arise as a common trunk from the main intercostal nerve. A comparison of the intercostal nerve ramification with that in man is included. PMID- 8434509 TI - Postnatal development of skull base, neuro- and viscerocranium in man and monkey: morphometric evaluation of CT scans and radiograms. AB - Postnatal development of the neuro- and viscerocranium with special reference to the maxillodental structures was studied morphometrically by analyzing computer tomograms and radiograms of human and monkey heads of different age groups. The following parameters were used: the prognathic angle, the clivus angle, the palate-incisivus angle, the interincisival angle and the viscerocranial quotient. In the newborn primates including man, all parameters measured were relatively similar; postnatally, however, characteristic differences in the growth pattern between man and monkey were developing. In monkey, a marked prognathic growth of the viscerocranium was found associated with characteristic positional changes of the frontal teeth, whereas the growth of the neurocranium was retarded. Here, unlike the human, a flattening of the skull base was observed. In contrast, the human skull showed no major proportional changes during its postnatal development compared with the original spherical skull form of the newborn. PMID- 8434512 TI - De novo aneurysm formation and aneurysm growth following therapeutic carotid occlusion for intracranial internal carotid artery (ICA) aneurysms. AB - We herein report the long term results of 27 intracranial internal carotid artery (ICA) aneurysms treated by indirect surgery such as a trapping of the aneurysm or carotid ligation either with or without EC-IC bypass. These patients were then followed for a mean period of 10 years. Seventy-four percent of the aneurysms were categorized as either being giant or large. Late complications were observed in 7 patients. A rupture of newly formed aneurysms at the anterior communicating artery occurred in 2 cases 8 or 9 years after either trapping or performing a ICA ligation, respectively. In these patients, previous angiography could not reveal any abnormalities at the anterior communicating artery. A rupture of a contralateral ICA aneurysm was seen in a patient whose ipsilateral ICA was ligated for a ICA aneurysm 22 years previously. An enlargement of the contralateral giant cavernous ICA aneurysm became symptomatic 6 years after a partial ligation of the ICA combined with an EC-IC bypass for a giant cavernous carotid artery aneurysm on the other side. Two cases of sudden death occurred in a young patient and an elderly patient with a small anterior communicating artery aneurysm, 9 and 19 years respectively, after trapping of the ICA aneurysms, although the cause could not be definitely ascertained. Rebleeding occurred in one patient who died 8 years after a carotid ligation and a partial clipping of the ICA aneurysm. Haemodynamic stress may therefore play a major role in inducing new aneurysms or growing aneurysms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8434511 TI - Aneurysms of the anterior inferior cerebellar artery. AB - Aneurysms of the anterior inferior cerebellar artery (AICA) are rare lesions. Three AICA aneurysms that differed in clinical presentation, anatomical location, and morphology are presented to illustrate the radiologic evaluation, perioperative management, surgical treatment and prevention of complications of these uncommon lesions. PMID- 8434510 TI - Morphological and haemodynamic aspects of cerebral aneurysms. AB - 4 patients with aneurysms of different size and location were examined by cerebral angiography, computed tomography, angio-computed tomography, magnetic resonance imaging and angiography, in order to demonstrate haemodynamic and morphological aspects of cerebral aneurysms. Turbulent flow within aneurysms could be shown by cerebral angiography and magnetic resonance angiography. In contrast MRI or computed tomography are necessary to visualize additional thrombosed parts. MRI is the method of choice to reflect the formation of thrombus, CT to show possible calcifications. PMID- 8434513 TI - Arteriovenous malformation and diaschisis. AB - We investigated the haemodynamic dysfunction and secondary thalamic and brainstem atrophy in 24 patients with angiographically proven cerebral arteriovenous malformations (AVM) and no clinical history of cerebral haemorrhage. Cerebral blood flow (CBF) was measured by the method using either stable Xenon or single photon emission computerized tomography (SPECT). Morphological changes in the thalamus and brainstem were evaluated by magnetic resonance imaging (MRI). Two factors are considered to influence hypoperfusion in the ipsilateral cerebral and contralateral cerebellar hemisphere and secondary atrophy of the thalamus and brainstem. One is the size of the nidus and the other is the involvement of the basal ganglia. It is presumed that continuous haemodynamic stress over a long period of time may cause irreversible histological changes in areas remote from the lesion, especially in the AVM which demonstrates involvement of the basal ganglia or a large nidus. PMID- 8434514 TI - Cerebral venous angiomas: surgery as a mode of treatment for selected cases. AB - Eleven patients with venous angiomas, 6 males and 5 females ranging in age from 4 to 58, are presented. Four patients presented with intracerebral haematoma and 3 patients had associated cavernous angioma, respectively. Patients with intracerebral haematoma had signs and symptoms due to the localization of the haematoma. The other patients presented with headache, seizures, vertigo, ataxia and mental disturbances. Pre-operative diagnosis was based on computerized tomography, magnetic resonance imaging and cerebral angiography. In 9 surgical cases it was confirmed by histopathological examination of operative specimens. After establishing the type, size and location of the lesion decision for operative treatment was made in nine cases, in four of them because of the presence of an intracerebral haematoma and in 5 of them due to severe disability. Eight of these 9 patients recovered completely and one improved. No severe cerebral oedema was encountered after converging medullary veins were excised and main draining veins partially coagulated. In this small series we encountered an unexpectedly large percentage of venous angiomas causing intracerebral haemorrhage which are commonly considered more benign than other vascular malformations. After reviewing previously reported cases of venous angiomas causing intracerebral haemorrhage and severe neurological deficit we think that the term "benign" is worth reconsidering. We propose a thorough examination of each case of venous angioma and the operative treatment when appropriate taking into account patients state and location of angioma. PMID- 8434515 TI - Continuous irrigation-drainage of the subdural space for the treatment of chronic subdural haematoma. A prospective clinical trial. AB - Thirty seven adult patients which chronic subdural haematoma were randomized into two groups. Eighteen patients served as controls and underwent evacuation of the haematoma via burr holes and a gravity dependent closed-system drainage. Nineteen patients comprised the study group. These patients had a continuous irrigation drainage system installed in an attempt to facilitate the removal of fibrinolytic substances present in the haematoma fluid and to try to reduce the rate of rebleeding from the haematoma membranes. No differences were found between the pre- and post-operative clinical status, haematoma volumes and the degree of CT changes between the two groups. The complication rate was similar in the two groups. One patient in the study group and three patients in the control group required an extended period of drainage (24-48 hours) prior to the removal of the drains. All patients improved following the procedures. Within 30 days post the initial evacuation of the chronic subdural haematoma, re-operation was required in only one patient in the study group as opposed to four of the controls. This difference was not however statistically significant. When the need for re operation was combined with the need for extended drainage period, a significant difference was shown in favour of the study group. These results indicate that drainage combined with continuous irrigation of the subdural space does not affect the clinical outcome of the patients, but significantly reduces the frequency of inadequate drainage of the haematoma and prevents longer drainage periods and repeated operations. PMID- 8434516 TI - Computed tomography features immediately after replacement of haematoma with oxygen through percutaneous subdural tapping for the treatment of chronic subdural haematoma in adults. AB - In an effort to achieve a simple and less invasive method for the treatment of chronic subdural haematoma, replacement of the haematoma with oxygen by percutaneous subdural tapping was employed in 36 patients. This study was conducted on 23 haematomas in 20 patients, whose computed tomography (CT) scans immediately following the treatment were available for evaluation, with particular regard to distinguishing between their findings and those seen with tension pneumocephalus. The CT features were divided into two patterns according to the location of oxygen; a convexity type (19 haematomas) and an interhemispheric type (4 haematomas). Analysis of the CT appearances revealed the oxygen was exclusively confined to the haematoma cavity, distinguishing it from the findings in tension pneumocephalus. This observation indicates the safety of replacement of the haematoma with oxygen when combined with our percutaneous subdural tapping technique which prevents lesions of the inner haematoma membrane. PMID- 8434517 TI - Conservative management of extradural haematomas. AB - The personal experiences with a series of 57 conservatively treated extradural haematomas (EDH) are presented and the criteria for conservative management outlined. Main preconditions are absence of neurological deficit, close clinical supervision and repeated CT check-ups. PMID- 8434518 TI - The acrylic-wire option in cervical spine fixation. A retrospective study. AB - This retrospective study was undertaken to assess the stability of the cervical spine after fixation with acrylic wire implants. Of the 44 patients with various pathological conditions of the cervical spine selected for this treatment in the course of 20 years, 36 were considered suitable for long-term follow-up evaluation. In 30 cases (83%) the stability of the spine was rated good. It is concluded that the acrylic-wire combination is a valuable surgical option in certain conditions i.e. old age, short life expectancy, poor general health, mental disease, in which long confinement in bed or in orthopaedic appliances is poorly tolerated. PMID- 8434519 TI - A reproducible model of reversible, focal, neocortical ischemia in Sprague-Dawley rat. AB - A reproducible model of reversible, focal ischemia was developed for use with the normotensive, Sprague-Dawley rat. Blood flow to the left cerebral hemisphere was interrupted by occluding simultaneously the left middle cerebral artery and both carotid arteries (CCA). The arterial occlusion lasted for 1, 2 or 3 hours after which animals survived for 3 days. The volume of brain infarction was determined utilizing computer-assisted measurements of serial brain sections stained with triphenyltetrazolium. Tissue infarctions of variable size were observed following arterial occlusions which persisted 1 or 2 hours. In contrast, remarkably consistent infarction size was obtained following a three hours period of occlusion. Tissue edema was also estimated by measuring the volumes of the two hemispheres and expressing these values as a ratio for each animal. The volume ratio was significantly greater in the 3 hour ischemic group, indicating the occurrence of edema in the infarcted hemisphere. These results demonstrate that reversible vascular occlusion in the normal, Sprague-Dawley rat results in consistent amounts of tissue infarction. This approach represents an attractive model system for studying the pathophysiological effects of transient, focal ischemia and for testing the effects of putative, therapeutic strategies. PMID- 8434520 TI - Orbital pain and unruptured carotid-posterior communicating artery aneurysms: the role of sensory fibers of the third cranial nerve. AB - Intact aneurysms of the carotid siphon at the point of take-off of the posterior communicating artery may exhibit orbital pain, whether associated with oculomotor palsy or not as a warning symptom prior to rupture. In order to explain this symptom the hypothesis of a sensory pathway within the third cranial nerve, which is liable to compression by the enlarging aneurysm sac, has been investigated. Data from human autopsy material show evidence of sensory ganglion cells within the rootlets of the oculomotor nerve; furthermore, studies in animals prove that the third nerve contains sensory fibers which run proximally along the nerve bundles, enter the brainstem and reach the spinal trigeminal nucleus. These fibers come from the ophthalmic division of the fifth nerve and join the third nerve at the level of the lateral wall of the cavernous sinus. Although a number of questions remain to be solved, the presence of a sensory pattern within the third nerve could account for fronto-orbital pain from enlarging aneurysms impinging on the third nerve itself. PMID- 8434522 TI - Vein graft replacement of the distal vertebral artery. AB - Vein graft reconstruction of the cervical portion of the vertebral artery has been commonly used for the treatment of atherosclerotic arterial disease. In this article, we describe two instances of vein graft replacement of the distal portion of the vertebral artery. In the first case, the vein graft was placed from C2 transverse foramen to the intradural portion of the vertebral artery to replace an artery abnormally encased and involved by meningioma. The grafting was done in this case to preserve the cerebrovascular reserve in a young patient. In the second case, a vein graft was placed from the extradural C1 portion to the intradural artery beyond the posterior inferior cerebellar artery. This was done to replace a segment of the artery involved by a giant aneurysm, which could not be clipped without occluding the parent artery. In this case, the vein graft replacement was necessitated by changes of somatosensory evoked potentials after the aneurysm was clipped, demonstrating the need to preserve the patency of the artery. Vein graft replacement of the proximal intradural vertebral artery is feasible by the combination of standard cerebro-vascular techniques and the exposures afforded by skull base surgery. PMID- 8434521 TI - Relationship between blood flow and blood-brain barrier permeability of sodium and albumin in focal ischaemia of rats: a triple tracer autoradiographic study. AB - Local cerebral blood flow, the permeability of the blood-brain barrier to sodium and serum albumin, and the content of electrolytes were investigated in rats before and at 4 h and 24 h following permanent occlusion of the middle cerebral artery (MCA). Measurements were carried out by triple tracer autoradiography, using 131I-iodoantipyrin, 22NaCl and 125I-iodinated bovine serum albumin, respectively. Regional sodium and albumin transfer coefficients were calculated by multiple time point analysis, and correlated with the corresponding flow and tissue electrolyte values. In sham operated controls regional sodium and albumin transfer coefficients ranged between 2.16-2.30 x 10(-3) and 0.22-0.48 x 10(-3) ml/min per g, respectively. Four hours after MCA occlusion sodium and albumin transfer coefficients were unchanged although tissue sodium content was already increased. After 24 h the sodium-but not albumin-transfer coefficient increased 2 3 fold but the rise in tissue sodium content was slower than after 4 h. At both ischaemia times the unidirectional sodium influx was substantially higher than the actual changes of tissue sodium content. The development of stroke oedema is, therefore, not limited by the alterations of barrier permeability. PMID- 8434523 TI - Successful treatment of increased intracranial pressure by barbiturate therapy in a patient with severe sinus thrombosis after failure of osmotic therapy. A case report. AB - A patient with sinus thrombosis and characteristic magnetic resonance imaging (MRI) findings, who was managed successfully by barbiturate therapy is reported. MRI showed massive high intensity lesions on T2-weighted image which indicated venous cerebral infarction and brain oedema. Intravenous infusion of thiopental decreased increased intracranial pressure (ICP). The effectiveness of barbiturate therapy is discussed in terms of the similarity between this case and experimental sinus thrombosis. Barbiturate therapy should be considered in cases of severe sinus thrombosis with elevated ICP. PMID- 8434524 TI - Bilateral chronic subdural haematomas following traumatic cerebrospinal fluid leakage into the thoracic epidural space. AB - This report describes a patient who developed bilateral chronic subdural haematomas after a stab injury to the thoracic meninges causing prolonged cerebrospinal fluid leakage into the epidural space. Diagnostic findings and therapeutic management are presented and possible pathogenic mechanisms are discussed. This case suggests that patients who have symptoms or signs of increased intracranial pressure after a penetrating spinal injury should be studied for subdural haematoma. PMID- 8434525 TI - Significant lateralisation of supratentorial ICP after blunt head trauma. PMID- 8434527 TI - [Retinal pigment epithelial cell culture and transplantation]. PMID- 8434526 TI - The new antibody technologies. PMID- 8434528 TI - [What is the present best scale to estimate infants' prematurity to predict retinopathy of prematurity? Aichi Retinopathy Study Group]. AB - The present study is the second report using the data of the epidemiological survey of retinopathy of prematurity (ROP) obtained during the 2 year period 1986 1987 in Aichi Prefecture. To study ROP we have used birthweight and gestational age for estimation of infants' prematurity. These two parameters were found to have a very close relation with the incidence of ROP. Although gestational age is close to the embryonic age, birthweight is greatly influenced by intrauterine environmental factors. To confirm the importance of using birthweight, the relationship between the incidence of ROP and the influence of intrauterine environmental factors must be close. Using data on 1,887 premature infants, the mean and standard deviation of birthweight in each gestational weeks were calculated. Deviation of birthweight was considered to reflect the influence of intrauterine environmental factors and was evaluated by comparing the birthweight of a baby with the mean birthweight for the same number of gestational weeks. The incidence of ROP had no close relationship with the deviation of birthweight at each gestational age. Therefore, it was concluded that the influence of the modifying factors of birthweight had not any close relation with the incidence of ROP. At present we should use gestational age as the best scale to estimate infants' prematurity to predict ROP. PMID- 8434529 TI - [Light-induced dephosphorylation of phosphoproteins in rod outer segments in bovine and frog retina]. AB - Several lines of evidence have suggested that protein phosphorylation and dephosphorylation may play an important role in the regulation of metabolism and signal transduction processes. In our present study, bovine and frog retinas were incubated in Krebs' solution containing [32P] H3PO4 for the labelling of all phosphoproteins. Then, photoreceptor outer segments were isolated from each retina, and further incubated under dark or light conditions. In such conditions, several phosphoproteins were dark- or light-dependently dephosphorylated. Interestingly, the light-dependent dephosphorylated 39 kDa protein as well as the 35-36 kDa protein was commonly observed in both bovine and frog retinas. The 35 36 kDa protein is considered to be the same as the 33 kDa protein that has previously been shown to be phosphorylated light-dependently, whereas 39 kDa protein is thought to be a novel protein that undergoes light-dependent dephosphorylation in retinal photoreceptor outer segments. Thus, these proteins were thought to have significant roles in the visual transduction processes. PMID- 8434530 TI - [Optic disc measurements for cup depth with computerized image analysis in normal subjects and case of ocular hypertension and glaucoma]. AB - Computerized image analysis was performed in 46 normals subjects and in 47 cases of ocular hypertension and 48 cases of early glaucoma for optic disc cup depth and optic disc parameters (rim area, cup area, cup volume and cup/disc ratio). The optic disc cup depth was 369.6 +/- 18.2 microns (M +/- SEM) in normal subject, 538.3 +/- 24.0 microns in ocular hypertension cases, 675.0 +/- 24.7 microns in glaucoma cases. The cup depth was significantly different among the three groups. The quotient of horizontal to vertical cup/disc ratio was also significantly different among the groups (1.84 +/- 0.17 in normal subjects, 1.28 +/- 0.05 in ocular hypertension cases, and 1.120 +/- 0.03 in glaucoma cases.) These results demonstrate that the optic disc cup enlarges three-dimensionally in early glaucoma. PMID- 8434531 TI - [Statistical study of ocular injuries--effect of the seat belt legislation in traffic ocular injuries]. AB - Three hundred and eighty cases of eye injuries treated at Kyushu University Hospital during from January, 1984 to December, 1989 were statistically analyzed. Ocular injuries comprised about 10% of the total number of in-patient cases. Males were five times more than females. Among the age groups, those in their teens were the most affected. The most frequent cause of injuries was blunt trauma in sports. The effect of the seat belt legislation in November 1986 in traffic ocular injuries was examined. Traffic ocular injury cases were about 20% of all cases of ocular injuries. In the ocular injury, perforating injury was the most among traffic eye injuries and the visual outcome was poor. However, after the seat belt legislation the rate of traffic ocular injuries in total ocular eye injuries decreased from 26% to 14%. Furthermore, the incidence of perforating eye injuries caused by shattering windshields decreased significantly and the final visual acuity was better than before legislation. From these results, we conclude that the seat belt legislation has been effective in decreasing traffic eye injuries. PMID- 8434532 TI - [A modification of the Aulhorn flicker test with results of physiological and pathological conditions]. AB - The Aulhorn flicker test measures the subjective brightness of various frequencies of flickering light. We modified an Aulhorn flicker test with light emitting diode (LED) and the results of 21 normal eyes and 18 affected eyes (7 eyes with idiopathic optic neuritis, one eye with rhinogenous optic neuropathy (ethmoid sinus mucocele), two eyes with preoperative pituitary tumor, one eye with empty sella, one eye with anterior ischemic optic neuropathy, one eye with syphilitic optic neuritis, five eyes with primary open angle glaucoma) were presented. All normal eyes showed the Brucke-Bartley effect which refers to an enhanced subjective brightness at lower frequencies. Six eyes with idiopathic optic neuritis and one eye with rhinogenous optic neuropathy in the acute stage demonstrated the Aulhorn effect which refers to a reduced subjective brightness at lower frequencies. Four eyes with the Aulhorn effect that were followed up showed less prominent Aulhorn effect. One eye with idiopathic optic neuritis and 10 eyes with other conditions did not show the Aulhorn effect. It was suggested that the modified Aulhorn flicker test with LED is a useful method for diagnosis of optic neuritis in the acute stage. PMID- 8434533 TI - [HTLV-I associated myelopathy with macular degeneration]. AB - The authors report a case of macular involvement in a patient with HTLV-I associated myelopathy (HAM). The patient was a 10-year-old girl who noticed sudden decreased vision in her right eye in November 1987. The corrected visual acuity was 0.01 in the right eye and 1.0 in the left eye. Fundus examination of the right eye disclosed mild optic disc pallor. The macula appeared to have pigmentary mottling with superficial irregular retinal reflex that was three disc diameters in size. Fluorescein angiography revealed a discoid hypofluorescent area in the macula, surrounded by mottled hyperfluorescent areas. She had no contributory family history of ocular disease, but had a history of blood transfusion during an operation for patent ductus arteriosus and ventricular septal defect at the age of 8 months. In November 1990, she developed gait disturbance due to spastic paraparesis and was admitted to our hospital. Antibodies to HTLV-I were markedly elevated in serum (titer, 1:8192) and in cerebrospinal fluid (titer, 1: 1024). She was diagnosed as HAM. Two months later, she developed encephalopathy and bilateral optic disc atrophy. PMID- 8434534 TI - [Changes in the intermediate stage of retinal degeneration after intravitreal injection of ornithine]. AB - We reported previously that intravitreal injection of a small amount of 1 ornithine hydrochloride in monkey eyes damages the retinal pigment epithelium (RPE), selectively. At one year after administration, sharply demarcated chorioretinal atrophy was seen. This paper describes the intermediate stage of retinal degeneration caused by ornithine. Two weeks following intravitreal injection of ornithine, RPE cells at the equator became necrotic and disappeared. However RPE regenerated to cover Bruch's membrane at the border of RPE degenerated area. In 2 months at an area where RPE cells disappeared, the photoreceptors and choriocapillaris degenerated to disappear. However, in the area in where RPE regenerated, they maintained their structure. This report demonstrated that damage of RPE resulted in disappearance of the photoreceptor and choriocapillaris. PMID- 8434535 TI - [Human cultured retinal pigment epithelial cells produce interleukin-6]. AB - Production of interleukin 6 (IL-6) from cultured human retinal pigment epithelial cells (RPE) was demonstrated using an enzyme-linked immunosorbent assay. Production of IL-6 occurred without any stimulation and significantly increased approximately 2-5 times by lipopolysaccharide (LPS) or interleukin 1 alpha stimulation. Hydrocortisone reduced the production of the LPS-stimulated IL-6 to a half level. Both gel filtration and western blotting analysis indicated the molecular weight of IL-6 as 30,000-35,000. IL-6 produced in the RPE may play a role in amplifying ocular immune and inflammatory responses. PMID- 8434536 TI - [Assessment of anti-proliferative and anti-inflammatory drugs for treatment of ocular fibroblast proliferation using dynamic microscope image processing scanner]. AB - Controlling ocular fibroblast proliferation may significantly improve the effectiveness of glaucoma filtration surgery. Drugs for the inhibition of fibroblast growth are currently in clinical use. However, systemic studies of drugs with different mechanisms of action have not been performed on human ocular fibroblasts. We have developed a method to evaluate the effect of chemotherapeutic agents on fibroblast proliferation, motility, and dynamic morphology. This involves the use of an automated microscope system designed for quantitative measurement of movement and morphology of live cells in tissue culture. This technique was tested on an established tissue culture fibroblast (3T3 cells) and then applied to secondary culture of human scleral and subconjunctival fibroblasts. 5-fluorouracil and colchicine were tested for their effect on fibroblast behaviour. Our data indicated that colchicine was more effective than 5-fluorouracil in inhibiting fibroblast proliferation and movement, and in changing morphology. Using this system, fundamental biological effects of various pharmacological manipulations could be studied in vitro prior to in vivo applications. PMID- 8434537 TI - [Effect of neonatal retinal pigment cell transplantation on aged retinas]. AB - The authors performed neonatal healthy retinal pigment epithelium (RPE) transplantation into older eyes to test whether aging changes could be deterred or arrested in an appropriate model. Fischer-344 rats, a model for studying age related photoreceptor cell death, were used as the recipient and 6- to 8-day-old Long Evans rats were used as the donor of neonatal RPE. Isolated RPE cells were transplanted into the subretinal space in 24, 3-month-old Fischer-344 rats. The presence of healthy neonatal RPE cells significantly maintained the thickness of each layer as compared to the findings in nongrafted and sham operated controls at 3 and 6 months after the transplantation. The transplanted RPE cells saved the reduction of cell population caused by aging from 40% to 17% in the outer nuclear layer and from 33% to 8% in the inner nuclear layer at 6 months after transplantation. PMID- 8434538 TI - [Expression of modified nucleoside, 1-methyladenosine in intraocular tumors and the retinas]. AB - 1-methyladenosine is one of the modified nucleosides, the levels of which are elevated in urine of patients with malignant tumors. We report herein immunohistological expression of 1-methyl-adenosine in tumor cells and retinas. Eight retinoblastomas, 4 malignant melanomas, two metastatic choroidal tumors, 3 retinal dysplasias, one intraocular hemorrhage and 5 normal eye retinas in human were examined. In addition, 8 experimental rabbit choroidal tumor XV2s, and 5 normal rabbit retinas were examined. 1-Methyladenosine was expressed in almost all malignant tumors and retinas with these tumors, while there was little expression in benign tumor cells, retinas with benign tumor and retinas in normal eyes. Results in rabbits were almost the same as in humans. Examination of expression of 1-methyladenosine is expected to be useful for the histological diagnosis of intraocular tumors. PMID- 8434539 TI - [The effect of organophosphorus pesticide (fenthion) on GABA-cells in the central nuclei]. AB - Organophosphorus pesticide (OP) produces abnormal eye movements. This is possibly due to an inhibition of central cholinergic neurons as well as GABAnergic neurons. Using anti-GABA-antibody, the authors studied the effect of OP on GABA positive cells in the central nervous system. Fenthion (dimethyl 4-methylthion-m tolyl-phosphorothionate, 20 mg/kg body weight), was given subcutaneously to the dorsal portion of Wistar rats for 30 days. After staining, the number of GABA positive cells were counted at the superior colliculus (SC), the cerebellum, and the substantia nigra reticularis (SNR) on day 6, 10, 14, 18, 22, 26 and 30 respectively. The number of GABA-positive cells reduced in the cerebellum, SNR and SC decreasing remarkably after the initiation of fenthion administration. The number of GABA-positive cells also decreased in lateral geniculate nucleus and pretectal nuclei. Those results suggest that the reduction of GABA-positive cells produces abnormal eye movements in human OP intoxication. PMID- 8434540 TI - [Measurement of the radius of corneal curvature with the Maloney surgical keratometer and an on-line keratometer imagery processing system]. AB - A system for measuring the radius of the corneal curvature using the Maloney surgical keratometer (Keratoring), designed for prescribing contact lenses in cases in which it is not possible to measure the radius of the corneal curvature by conventional methods, was tested, and its precision and practicality were evaluated. The subjects were 67 eyes in 34 healthy adults and steel globes for photokeratometer calibration with radii of curvature of 6.73 mm, 7.91 mm and 9.07 mm. The Placido ring projected by the Keratoring was first transmitted to video image processing board via a video unit, and the image was analyzed using a program developed by the authors. Measurements of the globes were possible within a range of error of +/- 0.05 mm, enabling extremely precise analysis. Furthermore, when the average radius of the corneal curvature of human corneas was measured, deviation from the ophthalmometer reading was within 0.2 mm in 87% of cases. When minor meridians were compared, it was found to be possible to measure to within 0.3 mm in 90% of cases. It therefore appears appropriate to apply this method as an index for prescribing contact lenses, especially in cases where conventional methods cannot be performed. PMID- 8434541 TI - [IOP change over time in normal-tension glaucoma]. AB - The authors retrospectively studied intraocular pressure (IOP) changes over time in normal-tension glaucoma (NTG). The materials consisted of 160 eyes of 80 patients who fulfilled the diagnostic criteria for NTG including a continuous daily IOP profile of less than 21 mmHg. They were followed for 12 to 64 months (mean: 31 months) at 1 to 3 month intervals. Eleven eyes (6.9%) in 9 patients (11.3%) showed IOP equal to or greater than 21 mmHg at least once during the follow-up period. The probability of IOP remaining below 21 mmHg for 5 years was 89.1% for each eye and 80.6% for each case according to the Kaplan-Meier life table method. A discriminant analysis with stepwise variable selection revealed that higher maximum IOP in daily profile, positive history of diabetes mellitus, a family history of glaucoma, male sex, positive history of disc hemorrhage, low diastolic blood pressure, earlier visual field change and concordance in IOP and visual field were significant prognostic factors for subsequent IOP increase. PMID- 8434542 TI - [Combined posterior chamber intraocular lens implantation and trabeculectomy--a life-table analysis of postoperative clinical course]. AB - Postoperative courses of 68 eyes of 58 glaucoma patients who underwent posterior chamber intraocular lens implantation combined with trabeculectomy were studied retrospectively. The visual acuity was 0.5 or better in 66% of the eyes at 3 months postoperatively. The average intraocular pressure (IOP) was below 15 mmHg till 16 months postoperatively. An analysis of the postoperative course using the life-table method of Kaplan-Meier revealed that the probability of successful IOP control with medication was 83% at 18 months and 47% without medication. The subjects aged 75 years or older showed significantly higher success probability than those younger than 75 years, while types of glaucoma, the preoperative IOP control, location of conjunctival or sclerocorneal incision, postoperative 5 fluorouracil (5-FU) injections or surgical intervention on the iris had no significant effects on the probability of successful IOP control. The probability of subsistence of functional filtering bleb was 24% at 18-month follow-up, on which postoperative administration of 5-FU of 35 mg or more had a favorable effect. PMID- 8434543 TI - [Distribution and morphology of peripheral anterior synechia in primary angle closure glaucoma]. AB - We examined 91 patients (151 eyes) with primary angle-closure glaucoma (PACG) by pressure gonioscopy and studied the distribution and the morphology of peripheral anterior synechia (PAS). The incidence of the PAS were 85:7% in acute PACG, 47.1% in their fellow eyes and 86.6% in chronic PACG. The PAS in acute PACG were wider and taller than that of chronic PACG. The wide PAS were most common in the superior quadrant, and were more prevalent than the narrow PAS. The PAS as a whole was more frequently seen in the superior. The wide PAS was taller than the narrow PAS. The PAS indices showed no significant correlation with age but with duration of acute attack. PMID- 8434544 TI - [A prospective study on necessary and sufficient retinal photocoagulation for diabetic retinopathy]. AB - The present studies were performed to determine whether slight photocoagulation was better than heavy photocoagulation for the early stage of progressive proliferative diabetic retinopathy (PDR). The authors selected 17 patients who had bilateral PDR of equal severity (BI or BII stage according to Fukuda's classification). In every case, we randomly performed heavy photocoagulation (laser burns were 1142 +/- 179) to one eye and slight photocoagulation (405 +/- 166) to the other eye. More than 6 months after the last photocoagulation, the effects of these treatments were compared in both eyes by fundus pictures, visual acuity and posterior vitreous fluorophotometric values. The results of judgement by fundus pictures and by vitreous fluorophotometric values were in perfect agreement. Eight cases (47%) in whom eyes received slight photocoagulation showed result better than the other eye. Two cases (12%) which received heavy photocoagulation were better than the other eye. Seven cases (41%) showed the same level of severity. No significant differences were found between slight and heavy photocoagulation. PMID- 8434545 TI - [Changes of the diabetic retinopathy score]. AB - Changes of the retinopathy score with the progression of diabetic retinopathy were investigated in 87 eyes of 44 diabetic patients. The previously reported retinopathy scoring system of Yamashita et al., utilizing fluorescein angiography, was used. Factors relevant to an increase of the retinopathy score were determined using quantification analysis (a type of multivariate analysis). The factors assessed were microaneurysms, the extent of retinal nonperfusion, intraretinal microvascular abnormalities, the grade of fluorescein dye leakage from retinal vessels, neovascularization, the grade of macular edema, the HbA1c level and the duration of retinopathy. The retinopathy score increased in 50 eyes (57%) after a mean follow-up period of 24.9 months. The probability of the score increasing in the eyes with advanced background retinopathy was 78%. The probability in eyes with preproliferative or proliferative diabetic retinopathy was 52% or 11%, respectively. The mean increase of the score in one year was 3.0 for all subjects. The increase in the eyes with advanced background, preproliferative or proliferative diabetic retinopathy was 6.1, 2.8 or 0.1, respectively. Our results suggest that this scoring system can effectively detect changes of background and preproliferative retinopathy. According to quantification analysis, the factor most relevant to the increase of the score was retinal nonperfusion. Dye leakage and neovascularization were also relevant, in descending order. PMID- 8434546 TI - [Histological study on idiopathic epimacular membrane in three cases of different age]. AB - Histological features of idiopathic premacular membrane were studied in 3 cases of different ages. All cases were female and complained of blurred vision without any causative moment. The age was 7 year in Case 1, 29 year in Case 2 and 68 year in Case 3. The cases underwent vitreous surgery with easy removal of the membranes. On light and electron microscopical observation, the membranes composed of retinal glial cells, connective tissue and the inner limiting membrane in Case 1, fibroblastic cells and connective tissues in Case 2, and connective tissues and the inner limiting membrane lacking any cellular component in Case 3. These findings strongly suggest the possibility of existence of various pathogeneity and developmental stages and types in idiopathic epimacular membrane. PMID- 8434547 TI - Advanced life support in obstetrics course. PMID- 8434548 TI - A message from a substance abuser. PMID- 8434549 TI - Patient age and adequacy of Pap smears. PMID- 8434550 TI - Diary of a week in practice. PMID- 8434551 TI - Inflammatory bowel disease: Part I. Clinical features and diagnosis. AB - Familial and epidemiologic studies of inflammatory bowel disease indicate a strong genetic predisposition that is modified by certain environmental factors. Abnormal submucosal immune activation may be important in the etiology of the disease. Yersinia enterocolitica infection, various "gay bowel syndromes" and other recently described enteric infections often mimic Crohn's disease. An initial barium study is useful in documenting the extent of disease and complications. Endoscopic biopsy confirms the surface appearance and histologic features of inflammatory bowel disease. Newer photodocumentation techniques are expected to improve the comparability of endoscopic observations. Complications of inflammatory bowel disease occur frequently, may involve any organ system and may precede the onset of bowel symptoms. PMID- 8434552 TI - Assessing nutritional status in elderly patients. AB - The physician can incorporate nutritional assessment of the elderly patient into office practice by considering two questions. First, is the patient at nutritional risk due to disease, disability or medication? Second, is the patient at risk of disease and disability because of poor nutritional status? The four primary components of the nutritional assessment are summarized by the mnemonic ABCD, with A standing for anthropometric measurements such as height and weight; B for biochemical parameters such as the serum albumin level and the hemoglobin count; C for clinical evaluation, including an assessment of functional, social and mental status, the medical history and the physical examination, and D for dietary history, such as the use supplements and the adequacy of the diet. PMID- 8434553 TI - Polycyclic aromatic hydrocarbon toxicity. Agency for Toxic Substances and Disease Registry. AB - Because of the combustion of fossil fuels and organic waste, polycyclic aromatic hydrocarbons are ubiquitous in the environment. Some metabolites are believed to interact with DNA, causing malignancies and heritable genetic damage. Exposure to polycyclic aromatic hydrocarbons is associated with lung and skin cancers and, possibly, urologic, gastrointestinal, laryngeal and pharyngeal cancers. PMID- 8434554 TI - Henoch-Schonlein purpura. AB - Henoch-Schonlein purpura is a small vessel vasculitic disease thought to be caused by an immunoglobulin-mediated inflammatory process resulting from immune complex reaction to antigenic stimuli. It is a relatively common disease that will be encountered in the clinical practice of most family physicians. Although it occurs most frequently in children, it can occur in all age groups. It is classically manifested by palpable purpura on the lower extremities, abdominal pain, arthritis and renal involvement. Family physicians should be familiar with the disease's clinical manifestations and be aware of potentially serious complications that may affect long-term prognosis and management. PMID- 8434555 TI - ACOG issues report on ovarian cancer. PMID- 8434556 TI - The role of lipids and antioxidative factors for development of atherosclerosis. The Probucol Quantitative Regression Swedish Trial (PQRST). AB - The effect of probucol on the development of atherosclerosis is being investigated in the Probucol Quantitative Regression Swedish Trial (PQRST). Hypercholesterolemic patients are randomized to receive either probucol 0.5 g twice daily or placebo in a double-blind manner, in combination with dietary therapy and cholestyramine 8-16 g daily for a 3-year period. The primary endpoint of the trial is the change in atheroma volume, assessed by annual quantitative angiography involving 20-cm segments of the femoral artery. Data from the open diet and prerandomization phase indicate that probucol added to dietary intervention plus cholestyramine produced highly significant reductions in total (-17%), low-density lipoprotein (LDL; -10%), and high-density lipoprotein (-30%) cholesterol. From a subpopulation, LDL levels were isolated during different stages of the prerandomization phase. LDL was exposed to the oxidant Cu2+ and binding to fibroblasts as well as degradation by macrophages was measured. The generation of thiobarbituric acid-reactive substances (TBARS) was also measured. Probucol prevented degradation of copper-exposed LDL by macrophages and also reduced the formation of TBARS, indicating that probucol protected LDL from oxidation. After the trial concludes in December 1992, statistical models will be used to investigate how much of the change in atherosclerosis is explained by changes in lipoprotein concentrations and how much is explained by probucol's antioxidative effects. Thus, other metabolic factors such as dietary intake and circulating levels of lipid soluble vitamins and fatty acids that may modify the possible antioxidative effects of probucol are also measured and will be related to change in atherosclerosis. PMID- 8434557 TI - Femoral and coronary angiographic trials. AB - A number of large-scale clinical trials have demonstrated that lipid-altering therapy is associated with a reduced risk of coronary artery disease events. The mechanism of benefit has been postulated to be related to favorable effects at the level of the arterial wall. Angiography allows direct examination of the effects of lipid-altering therapy on the arterial wall and extensive angiographic trial data are now available. Coronary angiographic trials, employing various patient populations, therapies and endpoint measures, have demonstrated slowed progression and increased regression of atherosclerosis in the coronary tree. Femoral artery trials (which might be considered as surrogate for coronary artery trials) have also shown significant regression of atherosclerosis in treated patients. There are pros and cons for all of the various atherosclerosis change measurement techniques, but coronary artery disease events remain the "bottom line" of concern. In this regard, the Program on the Surgical Control of the Hyperlipidemias (POSCH) trial is valuable since the 3-year human consensus panel derived global coronary change score predicted subsequent coronary events. Yet to be determined are which quantitative coronary angiography measures predict events. Finally, given the number of therapeutic questions that remain, the most promising opportunity for future antiatherosclerosis research may lie in the use of ultrasound to evaluate changes in the carotid arteries. PMID- 8434558 TI - Glycation and oxidation: a role in the pathogenesis of atherosclerosis. AB - Reactions involving glycation and oxidation of proteins and lipids are believed to contribute to atherogenesis. Glycation, the nonenzymatic binding of glucose to protein molecules, can increase the atherogenic potential of certain plasma constituents, including low-density lipoprotein (LDL). Glycation of LDL is significantly increased in diabetic patients compared with normal subjects, even in the presence of good glycemic control. Metabolic abnormalities associated with glycation of LDL include diminished recognition of LDL by the classic LDL receptor; increased covalent binding of LDL in vessel walls; enhanced uptake of LDL by macrophages, thus stimulating foam cell formation; increased platelet aggregation; formation of LDL-immune complexes; and generation of oxygen free radicals, resulting in oxidative damage to both the lipid and protein components of LDL and to any nearby macromolecules. Oxidized lipoproteins are characterized by cytotoxicity, potent stimulation of foam cell formation by macrophages, and procoagulant effects. Combined glycation and oxidation, "glycoxidation," occurs when oxidative reactions affect the initial products of glycation, and results in irreversible structural alterations of proteins. Glycoxidation is of greatest significance in long-lived proteins such as collagen. In these proteins, glycoxidation products, believed to be atherogenic, accumulate with advancing age: in diabetes, their rate of accumulation is accelerated. Inhibition of glycation, oxidation, and glycoxidation may form the basis of future antiatherogenic strategies in both diabetic and nondiabetic individuals. PMID- 8434559 TI - Overview of current issues in management of dyslipidemia. AB - An ever-increasing body of evidence supports active intervention in patients with dyslipidemia. Newly formulated recommendations call for evaluation of and treatment decisions based on not only total cholesterol and low-density lipoprotein (LDL) cholesterol levels but also high-density lipoprotein (HDL) cholesterol and triglyceride levels. HDL cholesterol determinations are now encouraged as part of routine coronary risk assessment in healthy adults. In addition, both HDL cholesterol and triglyceride measurements are recommended in patients with coronary artery disease, cardiovascular risk factors, or potentially atherogenic disorders such as hypertension or diabetes. If hygienic measures fail to normalize lipid values, a variety of drugs may be used. Future management strategies may include novel agents that inhibit different steps in lipid metabolism or in cholesterol biosynthesis, drugs that modify the lipoproteins themselves rather than change their concentrations, and drugs that protect the vessel wall from atherogenesis. A problem still to be resolved is that only about 10% of candidates for antihyperlipidemic drug therapy are receiving such treatment. PMID- 8434560 TI - Antioxidants and lipid metabolism. Implications for the present and direction for the future. AB - Numerous angiographic trials have demonstrated that the atherosclerotic process can be modified through reductions in levels of low-density lipoprotein (LDL) cholesterol. Recent research has focused on other potential modalities by which atheroroma development might be inhibited. These newer strategies include reduction of the oxidative potential of LDL particles through modification of dietary fat intake; prevention of LDL oxidation through the use of antioxidants; and inhibition of monocyte and macrophage function by omega-3 fatty acids and leukotriene-1 antagonists. Inhibition of acyl-coenzyme A:cholesterol acyltransferase (ACAT) may block intestinal cholesterol absorption and reduce synthesis of very-low-density lipoprotein (VLDL), while simultaneously enriching high-density lipoprotein (HDL) cholesterol. Modification of cholesterol ester transfer protein may be associated with improved reverse cholesterol transport or enlarged HDL particles. In the future, a wide variety of therapeutic modalities may be available for use alone or in combination to reverse atherosclerosis or prevent its progression. PMID- 8434561 TI - A modern view of atherogenesis. AB - Two key events in the atherogenic cascade are the focal influx and accumulation of low-density lipoprotein (LDL) cholesterol at arterial sites having a predilection for atherosclerotic lesion development and the recruitment of blood monocytes to these lesion-prone sites. Both processes are enhanced in the setting of hyperlipidemia and dyslipoproteinemia. The monocytes recruited to the endothelial surface subsequently migrate to the subendothelial space under the directed guidance of chemoattractants, such as monocyte chemotactic protein-1 and oxidatively modified LDL. These cells then undergo activation-differentiation to become macrophages. At the same time, LDL, and probably other lipoproteins such as the small dense LDL particles and lipoprotein (a), traverse the endothelium and undergo oxidative modification by reactive oxygen species. These oxidatively modified lipoproteins are recognizable by the non-down-regulating macrophage scavenger receptor. Their uptake by these receptors results in the formation of the foam cell characteristic of early-stage atherosclerosis. As monocyte recruitment and lipoprotein influx continue, the lesion grows and develops into the fatty streak. Subsequent foam cell necrosis due to the influence of cytotoxic oxidatively modified LDL and increased collagen synthesis by intimal smooth muscle cells lead to the established atherosclerotic lesion referred to as the fibrous plaque. As our understanding of the mechanisms involved in the pathogenesis of atherosclerosis has evolved over the past few years, novel strategies for intervention in the atherogenic process have emerged. PMID- 8434562 TI - Brief hypnotic treatment of repetitive nightmares. AB - Little attention has been paid to repetitive nightmares and their direct treatment. Hypnosis appears to be a treatment of choice for these nightmares, and techniques for hypnotic treatment may be based upon whether the nightmare mirrors an actual experience of the patient. A new technique that reframes the waking point as the interrupted middle rather than the end of the dream, which then allows a benign completion, is presented, with case histories. PMID- 8434563 TI - Inner strength and other techniques for ego strengthening. AB - For most therapists who employ hypnoanalytic techniques, ego strengthening stands as the bedrock upon which other techniques are structured. Much ego strengthening takes place indirectly, and its effects are often perceived as improved therapeutic alliance, heightened insight, increased clarity of thinking, and/or improved self-esteem on the part of the patient. Since Hartland introduced ego strengthening techniques, most therapists have placed emphasis on formal ego strengthening procedures, both sentences and visualizations. More recently age progression procedures have been used for ego strengthening. In this paper we introduce the concept of "Inner Strength" as a helpful ego state, and we review three ways of helping the patient get in touch with inner resources in a way that strengthens the ego. We discuss relevant cases and present the appropriate scripts provided for implementing these techniques. PMID- 8434564 TI - Turning symptoms into allies: utilization approaches with posttraumatic symptoms. AB - Adult patients with symptoms connected to the trauma of childhood sexual abuse often present in therapy with multiple symptoms and life difficulties and offer a challenge to even the most experienced clinician. In this paper, I describe my work with three such patients who were crippled in different ways by symptoms that had proved resistant to years of various therapeutic interventions. In every case, I accepted and utilized these symptoms as positive resources for successful and rapid change. Patients were then taught self-utilization approaches which allowed them to sustain and extend initial improvements. I conclude that the indirect utilization principle introduced by Milton Erickson provides an effective method to use in approaching some of the more persistent patterns of posttraumatic symptomatology related to childhood sexual abuse. PMID- 8434565 TI - Enhancing the visualization of gymnasts. AB - Visualizations under hypnosis enabled nationally ranked Stanford male gymnasts to execute for the first time several complex tricks that they had been working on for over a year. The gymnasts were able to eliminate timing errors in the tricks, to increase flexibility, and, possibly, to concentrate strength. The rationale for the effectiveness of trance visualizations, the induction and deepening strategies used, and the effects are described. Also included is an example of the use of a translator for the induction of a subject with a minimal fluency in English. Implications for further use of hypnosis with athletes are suggested. PMID- 8434566 TI - Using hypnotherapy to overcome examination anxiety. AB - Eleven medical practitioners who had previously failed their fellowship examinations sought assistance in combating the anxiety that they felt had been responsible for their lack of success. They were seen individually for two, 50 minute sessions of hypnotherapeutic training designed to engender an increased confidence in their ability to overcome examination anxiety. Two outcome measures were used: the actual examination result and a face-valid attitude scale, the Examination Anxiety Thermometer. On the first of these, 10 of the 11 practitioners recorded passes, whereas on the second, 9 indicated an attitude change toward lower levels of test anxiety. Attention is drawn to the minimal expenditure of time involved in the treatment and the generalizability of the hypnotherapeutic technique to other areas of the practitioners' lives. PMID- 8434567 TI - Remission of dysphagia in a 9-year-old treated in a family practice office setting. AB - This case report demonstrates the effectiveness and practicality of hypnosis when used in a family practice office setting. I used my previously established rapport to induce a trance rapidly to evaluate a 9-year-old girl who came to my office with dysphagia that developed after choking on food. Her problem was resolved after three hypnotic sessions, accomplished during routine office visits. PMID- 8434568 TI - Toward a clearer definition of confounding. AB - Epidemiologists are aware that the estimated effect of an exposure can be biased if the investigator fails to adjust for confounding factors when analyzing either a prospective or retrospective etiologic study. Standard texts warn, however, that intervening factors are an exception: one should not adjust for any factor which is intermediate on the causal pathway between the exposure and the disease. Other factors which are not on the causal pathway but are caused in part by the exposure are often adjusted for in epidemiologic studies. This paper illustrates that bias can result when adjustment is made for any factor which is caused in part by the exposure under study and is also correlated with the outcome under study. Intervening variables are only one example of this phenomenon. The misleading effects of this practice are illustrated with examples. PMID- 8434569 TI - The role of exposure to animals in the etiology of Campylobacter jejuni/coli enteritis. AB - To determine the role of animals as possible sources for human infection with Campylobacter jejuni/coli, 218 human cases of Campylobacter enteritis diagnosed among members of Group Health Cooperative of Puget Sound, King County, Washington, from April 1982 through September 1983 were compared with 526 controls, randomly selected from Group Health Cooperative members. All subjects were questioned regarding animal exposures one week prior to illness (cases) or interview (controls). There was no increase in risk for C. jejuni/coli enteritis associated with contact with various animals. However, exposure to diarrheic animals was associated with a fourfold increase in the risk of C. jejuni/coli enteritis (odds ratio = 4.3, 95% confidence interval (CI) 1.9-9.7). Adjustment for potential confounding factors by logistic regression analysis yielded an odds ratio of 3.3 (95% CI 1.2-7.5) associated with such exposure. An estimated 6.3% of cases of C. jejuni/coli enteritis was attributed to exposure to diarrheic animals. PMID- 8434570 TI - The spectrum of acquired immunodeficiency syndrome (AIDS)-associated malignancies in San Francisco, 1980-1987. AB - Population-based disease registries for acquired immunodeficiency syndrome (AIDS) and cancer were linked for San Francisco residents to study the pattern of AIDS associated malignancies diagnosed during the time period 1980-1987. A total of 1,756 newly diagnosed malignancies were identified during these years among members of the AIDS cohort. Of these, 1,752 (99.7%) occurred in males, 1,454 (83%) were Kaposi's sarcoma, 235 (13%) were non-Hodgkin's lymphoma, and 16 (1%) were Hodgkin's disease. The distributions of AIDS patients with cancer differed significantly from those without cancer by race and by risk group. Malignancies known to be human immunodeficiency virus (HIV)-associated, and now diagnostic of AIDS (Kaposi's sarcoma, non-Hodgkin's lymphoma), were, as would be expected, dramatically in excess among AIDS patients. Some malignancies not traditionally thought to be HIV-associated appear to have occurred more often than expected in the study cohort. These include Hodgkin's disease, rare non-melanoma skin cancers, and cancers of the rectum, anus, and nasal cavity. Malignancies known to be HIV-associated were more likely to be diagnosed concurrent with or subsequent to first AIDS diagnosis. Conversely, malignancies not known to be HIV-associated were more likely to be diagnosed before AIDS diagnosis. Compared with the concurrent reference population of the San Francisco Bay Area, there was little or no increase in Kaposi's sarcoma over the time interval of this study. For non Hodgkin's lymphoma, and suggestively for Hodgkin's disease, however, the temporal increase has been quite dramatic. PMID- 8434571 TI - Prevalence of antibody to human T-cell lymphotropic virus type I in Okinawa, Japan, after an interval of 9 years. AB - To clarify events related to age dependence of human T-cell lymphotropic virus type I (HTLV-I) seroprevalence, the authors carried out two seroepidemiologic studies at a 9-year interval on residents of Yonaguni Island, Okinawa, Japan. The overall prevalence was 17.8% (345/1,943) in 1980 and 17.1% (264/1,543) in 1989 1990. The authors studied the relation of the HTLV-I infection rate to the birth year of 967 individuals tested in both years. Of the 967 individuals, 209 were positive for anti-HTLV-I in the 1980 survey. By the 1989-1990 survey, only 7 of the 758 anti-HTLV-I negative cases (0.9%) had become positive for anti-HTLV-I, and all 7 were over 40 years of age. For persons born in the same period, there was almost no difference between the prevalence of HTLV-I found in the 1980 survey and that found in the 1989-1990 survey. These data show that there were few new cases of HTLV-I infection and none in the lower age groups over the 9 years, which suggests that higher rates of HTLV-I infection in adults reflect past higher rates of infection as infants. PMID- 8434572 TI - Monocyte count: a risk factor for coronary heart disease? AB - Previous studies have reported total leukocyte count to be a risk factor for coronary heart disease. The pattern of association between each class of leukocytes and the onset of the disease was investigated in the Paris Prospective Study II. The study population consisted of 3,779 male French employees aged 29 52 years working in the Paris area and recruited between 1980 and 1985 (end of follow-up: June 1989). A high monocyte count was strongly associated with the risk of coronary heart disease after adjustment for tobacco use and the other classical risk factors for the disease. The monocyte-macrophage is known to play an important part in the development of atherosclerosis. A high monocyte count seems to predict the premature occurrence of a coronary event in middle-aged men. PMID- 8434573 TI - A case-control study of myocardial infarction in relation to use of estrogen supplements. AB - Observational epidemiologic studies suggest that the incidence of cardiovascular disease is reduced by about 50% in users of unopposed estrogens, but the reduction may have been overestimated because of a greater tendency for women at lower risk to use estrogens. To minimize bias due to such behavior, the authors conducted a case-control study of first myocardial infarction among Massachusetts women aged 45-69 years during 1986-1990, in which each of 858 cases was age matched with a control from the same geographic area, and important correlates of estrogen use and myocardial infarction were controlled by conditional logistic regression. The estimated relative risk was 0.9 for ever use of unopposed estrogen (95% confidence interval 0.7-1.2); the estimate decreased with increasing duration of use to 0.6 for 5 or more years of use (p for trend = 0.08). The association with long-term use was stronger for recent use (p for trend < 0.05) than for past use (p for trend = 0.86). There were insufficient data to evaluate estrogens taken together with progestins. The results suggest that unopposed estrogen use may reduce the risk of first myocardial infarction, that the reduction is related to the duration and recency of use, and that it may be smaller than previously believed. Despite efforts to control confounding, observational studies cannot rule out the possibility that a tendency for women at lower risk for myocardial infarction to use estrogens has contributed to the reduced risk in estrogen users, and randomized trials are needed. PMID- 8434574 TI - Black/white differences in hypertension in the elderly: an epidemiologic analysis in central North Carolina. AB - Hypertension in blacks, compared with whites, occurs at higher prevalence rates, is more severe, and carries a worse prognosis for cardiovascular morbidity and mortality. The authors examined the degree to which black/white differences in hypertension in the elderly are explained by demographic variables, income, health behavior (smoking, obesity), health service use, and comorbid diabetes. The study population consisted of subjects participating in the Duke site of the Established Populations for Epidemiologic Studies of the Elderly, initiated in 1984. Cross-sectional data reported here were collected between January 1986 and July 1987. Subjects were aged 65 years or older and were not institutionalized. Blacks were oversampled. Of 5,223 eligible persons, 4,163 (80%) agreed to be interviewed; 16% of the study subjects were white men, 30% white women, 19% black men, and 35% black women. The mean age for all groups was approximately 73 years. Forty-four percent of white men, 52% of white women, 50% of black men, and 66% of black women had hypertension. Eighty percent of hypertensives were receiving pharmacologic therapy. Older age, female sex, lower socioeconomic status, obesity, and diabetes mellitus were associated with hypertension. After adjusting for covariables, black race/ethnicity remained an independent risk factor for high blood pressure in the elderly, with an adjusted odds ratio of 1.30. PMID- 8434575 TI - Insulin-dependent diabetes mellitus, physical activity, and death. AB - The beneficial effect of physical activity in the general population is well known, but, to the authors' knowledge, has not been reported for persons with insulin-dependent diabetes mellitus. In a cohort of 548 diabetes patients followed as part of the Pittsburgh Insulin-dependent Diabetes Mellitus Morbidity and Mortality Study, physical activity was ascertained by survey in 1981, and mortality was ascertained through January 1, 1988. Cases were also compared with non-diabetic sibling controls. Activity level among cases varied inversely with the occurrence of diabetic complications. Overall activity level was inversely related to mortality risk. Sedentary males (< 1,000 kcal/week) were three times more likely to die than active males (> 2,000 kcal/week). A similar, but statistically nonsignificant, relation was seen in females. Cox proportional hazards analysis controlling for potential confounders (age, body mass index, insulin dose, reported diabetes complications, cigarette smoking, and current alcohol drinking) similarly revealed that activity level was inversely associated with mortality risk. Comparison of cases with non-diabetic sibling controls identified similar activity levels for the two groups. The results suggest that activity is not detrimental with regard to mortality, and may in fact provide a beneficial effect in terms of longevity in diabetes patients. PMID- 8434576 TI - Changes in adult cigarette smoking prevalence after 5 years of community health education: the Stanford Five-City Project. AB - To determine the effects of 5 years of community-wide cardiovascular health education on smoking prevalence and cessation, the authors analyzed data from the Stanford Five-City Project, an experimental field study with two treatment cities and two control cities. Representative samples of the population aged 12-74 years were drawn at baseline and every 2 years thereafter to obtain four independent cross-sectional surveys; participants aged 25-74 years are included in this paper (n approximately 440 per city per survey; total n = 6,981). The baseline sample was asked to return to three follow-up surveys, also 2 years apart, and those that did (n = 805) constitute the cohort survey sample. Self-reported cigarette smoking was confirmed by plasma thiocyanate and expired-air carbon monoxide levels. Smoking prevalence decreased over time in all cities, but in the cohort the decrease tended to be greater in treatment than in control cities (p = 0.10, two-tailed); the treatment-control difference was consistent over time (-1.51 percentage points/year in treatment vs. -0.78 percentage points/year in control, p = 0.007, two-tailed). In contrast, smoking prevalence in the independent samples declined similarly in treatment and control cities, changes were not linear, and rates varied within cities between times. Baseline smokers in both the cohort and the follow-up independent surveys were significantly more likely to quit in the treatment cities than in the control cities. PMID- 8434577 TI - The magnitude and variability of design effects for community intervention studies. AB - Despite inadequate replication of treatment and comparison groups in community intervention studies, suitable estimates of variance can be obtained by multiplying the simple random sampling variance by a design effect, which can be estimated from other sources. To study the stability of these estimates, the authors performed a detailed investigation of the magnitude and sources of variability of design effects for age-adjusted mortality rates for selected causes of death separately for each of 44 US states. The authors made use of age sex-race-county-specific data from the Compressed Mortality File generated by the National Center for Health Statistics. Design effects were calculated as the ratio of a cluster (county) sampling variance to the simple random sampling variance. The effects of sex, state, and year on the magnitude of the design effects were investigated by analysis of variance. Design effects were 2.33, 1.66, 1.24, 1.08, and 1.06 for ischemic heart disease, stroke, and cancers of the lung, breast, and colon, respectively. The largest source of variability was state; 35-70% of this variability could be attributed to the states' differing population sizes. The effect of sex was minimal. These results are relevant to the planning and analysis of community intervention studies. PMID- 8434578 TI - Child day care increases the risk of clinic visits for acute diarrhea and diarrhea due to rotavirus. AB - A case-control study of risk factors for acute diarrhea was conducted among children under 3 years of age attending a health maintenance organization clinic in Houston, Texas. During a 19-month period from September 1985 through March 1987, 339 children with diarrhea and 363 age- and season-stratified controls were enrolled. A total of 90% of cases were under age 2 years. Compared with children cared for at home, the risk of clinic visits for diarrhea was significantly greater for children receiving child day care and was similar for those attending day care centers (odds ratio (OR) = 2.4, 95% confidence interval (CI) 1.6-3.7), day care homes (OR = 2.0, 95% CI 1.3-3.1), mother's day out (OR = 1.8, 95% CI 0.8 4.2), or when cared for by a relative (OR = 2.0, 95% CI 1.2-3.2). Rotavirus positive diarrhea was also significantly greater in child day care (OR = 2.4, 95% CI 1.1-5.1). The day care-associated risk was highest during the first month of enrollment (OR = 3.1, 95% CI 1.8-5.4). In this population, where 40% of children receive child care, 19% of the clinic visits for acute diarrhea were attributable to child care. These data indicate that child day care increases the risk of acute diarrhea, whether in a center or in a home, and the risk is highest in the first month of enrollment. PMID- 8434579 TI - Unraveling the melanocyte. PMID- 8434580 TI - A duplicated region is responsible for the poly(ADP-ribose) polymerase polymorphism, on chromosome 13, associated with a predisposition to cancer. AB - The poly(ADP-ribose) polymerase (PADPRP) gene (13q33-qter) depicts a two-allele (A/B) polymorphism. In the noncancer population, the frequency of the B allele is higher among blacks than among whites. Since the incidence of multiple myeloma and prostate and lung cancer is higher in the U.S. black population, we have analyzed the B-allele frequency in germ-line DNA to determine whether the PADPRP gene correlates with a polymorphic susceptibility to these diseases. For multiple myeloma and prostate cancer, an increased frequency of the B allele appeared to be striking only in black patients. In contrast, the distribution of the B allele in germ-line DNA did not differ among white patients with these diseases, when compared with the control group. An elevated B-allele frequency was also found in germ-line DNA in blacks with colon cancer. These observations suggest that the PADPRP polymorphism may provide a valid marker for a predisposition to these cancers in black individuals. To determine the genomic structure of the polymorphic PADPRP sequences, a 2.68-kb HindIII clone was isolated and sequenced from a chromosome 13-enriched library. Sequence analysis of this clone (A allele) revealed a close sequence similarity (91.8%) to PADPRP cDNA (1q42) and an absence of introns, suggesting that the gene on 13q exists as a processed pseudogene. A 193-bp conserved duplicated region within the A allele was identified as the source of the polymorphism. The nucleotide differences between the PADPRP gene on chromosome 13 and related PADPRP genes were exploited to develop oligonucleotides that can detect the difference between the A/B genotypes in a PCR. This PCR assay offers the opportunity for analyzing additional black cancer patients, to determine how the PADPRP processed pseudogene or an unidentified gene that cosegregates with the PADPRP gene might be involved with the development of malignancy. PMID- 8434581 TI - Linkage analysis of "necessary" disease loci versus "susceptibility" loci. AB - The association of some diseases with specific alleles of certain genetic markers has been difficult to explain. Several explanations have been proposed for the phenomenon of association, e.g. the existence of multiple, interacting genes (epistasis) or a disease locus in linkage disequilibrium with the marker locus. One might suppose that when marker data from families with associated diseases are analyzed for linkage, the existence of the association would assure that linkage will be found, and found at a tight recombination fraction. In fact, however, linkage analyses of some diseases associated with HLA, as well as diseases associated with alleles at other loci located throughout the genome, show significant evidence against linkage, and others show loose linkage, to the puzzlement of many researchers. In part, the puzzlement arises because linkage analysis is ideal for looking for loci that are necessary, even if not sufficient, for disease expression but may be much less useful for finding loci that are neither necessary nor sufficient for disease expression (so-called susceptibility loci). This work explores what happens when one looks for linkage to susceptibility loci. A susceptibility locus in this case means that the allele increases risk but is neither necessary nor sufficient for disease expression. It might be either an allele at the marker locus itself that is increasing susceptibility or an allele at a locus in linkage disequilibrium with the marker. This work uses computer simulation to examine how linkage analyses behave when confronted with data from such a model.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8434582 TI - Cloning of functional alpha propionyl CoA carboxylase and correction of enzyme deficiency in pccA fibroblasts. AB - Propionyl CoA carboxylase (PPC) is a heteromeric enzyme composed of alpha subunits (PCCA) and beta (PCCB) subunits. We describe cDNA clones expressing human PCCA and complementation of the genetic defect in pccA fibroblasts by DNA mediated gene transfer. Two cDNA clones were constructed. The first corresponds to the previously reported, putatively full-length, open reading frame. The second encodes a chimera composed of the mitochondrial leader sequence of human methylmalonyl CoA mutase and the mature PCCA protein. Both clones reconstitute propionate flux to normal levels in fibroblasts from patients genetically deficient in PCCA (pccA). The maximal level of propionate flux approached, but never exceeded, the levels seen in control plates of normal cells. In contrast, the maximal level of PPC holoenzyme activity reached only 10%-20% that of normal controls, which corresponded roughly to the fraction of cells actually transformed with the recombinant gene. These data suggest that the level of PCCA expression in fibroblasts does not normally limit PCC holoenzyme activity or propionate flux. The fact that a small fraction of cells reconstitutes propionate flux to normal levels suggests that metabolic cooperation between cells is capable of increasing the metabolic capacity of recombinant enzyme in a subpopulation of cells. These factors may have important implications for the rational design of somatic gene therapy for PCCA deficiency. PMID- 8434583 TI - Germ-line origins of mutation in families with hemophilia B: the sex ratio varies with the type of mutation. AB - Previous epidemiological and biochemical studies have generated conflicting estimates of the sex ratio of mutation. Direct genomic sequencing in combination with haplotype analysis extends previous analyses by allowing the precise mutation to be determined in a given family. From analysis of the factor IX gene of 260 consecutive families with hemophilia B, we report the germ-line origin of mutation in 25 families. When combined with 14 origins of mutation reported by others and with 4 origins previously reported by us, a total of 25 occur in the female germ line, and 18 occur in the male germ line. The excess of germ-line origins in females does not imply an overall excess mutation rate per base pair in the female germ line. Bayesian analysis of the data indicates that the sex ratio varies with the type of mutation. The aggregate of single-base substitutions shows a male predominance of germ-line mutations (P < .002). The maximum-likelihood estimate of the male predominance is 3.5-fold. Of the single base substitutions, transitions at the dinucleotide CpG show the largest male predominance (11-fold). In contrast to single-base substitutions, deletions display a sex ratio of unity. Analysis of the parental age at transmission of a new mutation suggests that germ-line mutations are associated with a small increase in parental age in females but little, if any, increase in males. Although direct genomic sequencing offers a general method for defining the origin of mutation in specific families, accurate estimates of the sex ratios of different mutational classes require large sample sizes and careful correction for multiple biases of ascertainment. The biases in the present data result in an underestimate of the enhancement of mutation in males. PMID- 8434584 TI - Variations among Japanese of the factor IX gene (F9) detected by PCR-denaturing gradient gel electrophoresis. AB - In the course of feasibility studies to examine the efficiencies and practicalities of various techniques for screening for genetic variations, the human coagulation factor IX (F9) genes of 63 Japanese families were examined by PCR-denaturing gradient gel electrophoresis (PCR-DGGE). Four target sequences with lengths of 983-2,891 bp from the F9 genes of 126 unrelated individuals from Hiroshima and their 100 children were amplified by PCR, digested with restriction enzymes to approximately 500-bp fragments, and examined by DGGE--a total of 6,724 bp being examined per individual. GC-rich sequences (GC-clamps) of 40 bp were attached to both ends of the target sequences, as far as was feasible. Eleven types of new nucleotide substitutions were detected in the population, none of which produced RFLPs or caused hemophilia B. By examining two target sequences in a single lane, approximately 8,000 bp in a diploid individual could be examined. This approach is very effective for the detection of variations in DNA and is applicable to large-scale population studies. PMID- 8434585 TI - A frequent tyrosinase gene mutation associated with type I-A (tyrosinase negative) oculocutaneous albinism in Puerto Rico. AB - We have determined the mutations in the tyrosinase gene from 12 unrelated Puerto Rican individuals who have type I-A (tyrosinase-negative) oculocutaneous albinism (OCA). All but one individual are of Hispanic descent. Nine individuals were homozygous for a missense mutation (G47D) in exon I at codon 47. Two individuals were heterozygous for the G47D mutation, with one having a missense mutation at codon 373 (T373K) in the homologous allele and the other having an undetermined mutation in the homologous allele. One individual with negroid features was homozygous for a nonsense mutation (W236X). The population migration between Puerto Rico and the Canary Islands is well recognized. Analysis of three individuals with OCA from the Canary Islands showed that one was a compound heterozygote for the G47D mutation and for a novel missense mutation (L216M), one was homozygous for a missense mutation (P81L), and one was heterozygous for the missense mutation P81L. The G47D and P81L missense mutations have been previously described in extended families in the United States. Haplotypes were determined using four polymorphisms linked to the tyrosinase locus. Haplotype analysis showed that the G47D mutation occurred on a single haplotype, consistent with a common founder for all individuals having this mutation. Two different haplotypes were found associated with the P81L mutation, suggesting that this may be either a recurring mutation for the tyrosinase gene or a recombination between haplotypes. PMID- 8434587 TI - Which population? PMID- 8434586 TI - Constitutional 1p36 deletion in a child with neuroblastoma. AB - We describe a child with dysmorphic features, as well as developmental and growth delay, who developed neuroblastoma at 5 mo of age. Cytogenetic analysis of blood lymphocytes revealed an interstitial deletion of 1p36.1-->1p36.2, which was apparent only with high-resolution banding. Molecular analysis with a collection of polymorphic DNA probes for 1p confirmed an interstitial deletion involving subbands of 1p36. Deletions of this region are a common finding in neuroblastoma cells from patients with advanced stages of disease. Therefore, these results (a) suggest that constitutional deletion of this region predisposed the patient to the development of neuroblastoma and (b) support the localization of a neuroblastoma tumor-suppressor locus to 1p36. PMID- 8434588 TI - Paternal mutation of YNH24 (D2S44), a probe frequently used in paternity testing. PMID- 8434589 TI - Sex-specific recombination frequencies: a consequence of imprinting? PMID- 8434590 TI - Calculating the probability of observing b of a possible alleles at a marker locus. PMID- 8434591 TI - Robustness of the maximum-likelihood (LOD) method for detecting linkage. PMID- 8434592 TI - Defining the location of the Huntington disease gene. PMID- 8434593 TI - The evolution of a cytogenetics education program. AB - An educational program in clinical cytogenetics was initiated in 1983 at the University of Texas Health Science Center at Houston, through the Medical Technology Program in the School of Allied Health Sciences. Through the years the program has evolved into a more efficient curriculum, with the possibility of becoming a part of a master's degree program in allied health sciences. It is hoped that a description of the program will be of help to other educational institutions that may be contemplating the establishment of a similar course of study. PMID- 8434594 TI - Educating the medical community through a teratology newsletter. AB - To educate a geographically and professionally diverse group of health care providers about teratology in an economic and efficient manner, we developed a locally written and distributed teratology newsletter. Response to the newsletter, from readers as well as from our staff and funding agencies, suggests that such a newsletter can be a valuable tool in educating medical communities about teratology. PMID- 8434595 TI - Genetic science and education: attacks on ignorance: introduction to the education workshop. PMID- 8434596 TI - Genetics in medical education. PMID- 8434597 TI - Science education: the real challenge of reform. PMID- 8434598 TI - What does the public really need to know about genetics? PMID- 8434599 TI - Reaching the nonschool public about genetics. PMID- 8434600 TI - The Human Genome Project relevant to genetics education in high school. PMID- 8434601 TI - Re-aiming the canon. AB - Although it is unlikely that the national goals for educational reform--such as that, by the year 2000, U.S. students will be first in the world in science and mathematics achievement--can be achieved, a vigorous effort must be made to reach those goals as rapidly as possible. Reform will come not from a massive expansion of what we now do but from a basic shift in the manner in which we educate students in grades K-16 in the sciences and mathematics. Important elements in that basic shift must include an increase in teaching of science, mathematics, and technology (SMT), to about 20%-25% of the curriculum; SMT must include rich hands-on experiences, with an emphasis on concepts and understanding, rather than on facts and memorization, and on how science as a way of knowing differs from other ways of knowing; SMT must consider human problems; and SMT must deal with the basic problem facing humanity--how we must adjust our behavior so as not to exceed, on a worldwide basis, the carrying capacity of the environment. PMID- 8434603 TI - Human genetics: schoolyard experiences. PMID- 8434602 TI - Identification of the transcriptional unit, structural organization, and promoter sequence of the human sex-determining region Y (SRY) gene, using a reverse genetic approach. AB - Using a simple strategy involving cosmid-mediated gene transfer, cDNA library construction, and molecular characterization techniques, we have determined the transcriptional unit, structural organization, and promoter sequence of the human sex-determining region Y (SRY) gene, the putative testis-determining factor (TDF) gene on the human Y chromosome. By this approach, a recombinant cosmid harboring the human SRY sequence was isolated and transfected to appropriate tissue cultured cells. Recombinant cDNA clones were isolated from a cDNA library constructed from poly (A) + RNA of the transfected cells. Comparative studies between the respective cDNAs and the genomic cosmid have provided information regarding the organization of the SRY gene and its mRNAs. The results indicate that the human SRY gene is an intronless gene, produces transcripts of 1.1 kb, and possesses promoter activities in the transfected cells at approximately 310 bp of its upstream sequences. PMID- 8434604 TI - A second mutation in the type II procollagen gene (COL2AI) causing stickler syndrome (arthro-ophthalmopathy) is also a premature termination codon. AB - Genetic linkage analyses suggest that mutations in type II collagen may be responsible for Stickler syndrome, or arthro-ophthalmopathy (AO), in many families. In the present study oligonucleotide primers were developed to amplify and directly sequence eight of the first nine exons of the gene for type II procollagen (COL2A1). Analysis of the eight exons in 10 unrelated probands with AO revealed that one had a single-base mutation in one allele that changed the codon of -CGA- for arginine at amino acid position alpha 1-9 in exon 7 to a premature termination signal for translation. The second mutation found to cause AO was, therefore, similar to the first in that both created premature termination signals in the COL2A1 gene. Since mutations producing premature termination signals have not previously been detected in genes for fibrillar collagens, the results raise the possibility that such mutations in the COL2A1 gene are a common cause of AO. PMID- 8434605 TI - Identification of individuals by analysis of biallelic DNA markers, using PCR and solid-phase minisequencing. AB - We have developed a new method for forensic identification of individuals, in which a panel of biallelic DNA markers are amplified by the PCR, and the variable nucleotides are detected in the amplified DNA fragments by the solid-phase minisequencing method. A panel of 12 common polymorphic nucleotides located on different chromosomes with reported allele frequencies close to .5 were chosen for the test. The allele frequencies for most of the markers were found to be similar in the Finnish and other Caucasian populations. We also introduce a novel approach for rapid determination of the population frequencies of biallelic markers. By this approach we were able to determine the allele frequencies of the markers in the Finnish population, by quantitative analysis of three pooled DNA samples representing 3,000 individuals. The power of discrimination and exclusion of the solid-phase minisequencing typing test with 12 markers was similar to that of three VNTR markers that are routinely used in forensic analyses at our institute. The solid-phase minisequencing method was successfully applied to type paternity and forensic case samples. We also show that the quantitative nature of our method allows typing of mixed samples. PMID- 8434606 TI - Evaluation of standard error and confidence interval of estimated multilocus genotype probabilities, and their implications in DNA forensics. AB - Multilocus genotype probabilities, estimated using the assumption of independent association of alleles within and across loci, are subject to sampling fluctuation, since allele frequencies used in such computations are derived from samples drawn from a population. We derive exact sampling variances of estimated genotype probabilities and provide simple approximation of sampling variances. Computer simulations conducted using real DNA typing data indicate that, while the sampling distribution of estimated genotype probabilities is not symmetric around the point estimate, the confidence interval of estimated (single-locus or multilocus) genotype probabilities can be obtained from the sampling of a logarithmic transformation of the estimated values. This, in turn, allows an examination of heterogeneity of estimators derived from data on different reference populations. Applications of this theory to DNA typing data at VNTR loci suggest that use of different reference population data may yield significantly different estimates. However, significant differences generally occur with rare (less than 1 in 40,000) genotype probabilities. Conservative estimates of five-locus DNA profile probabilities are always less than 1 in 1 million in an individual from the United States, irrespective of the racial/ethnic origin. PMID- 8434607 TI - Manifestations of X-linked congenital stationary night blindness in three daughters of an affected male: demonstration of homozygosity. AB - X-linked congenital stationary night blindness (CSNB1) is a hereditary retinal disorder in which clinical features in affected males usually include myopia, nystagmus, and impaired visual acuity. Electroretinography demonstrates a marked reduction in b-wave amplitude. In the study of a large Mennonite family with CSNB1, three of five sisters in one sibship were found to have manifestations of CSNB1. All the sons of these three sisters were affected. Each of the two nonmanifesting sisters had at least one unaffected son. Analysis of Xp markers in the region Xp21.1-Xp11.22 showed that the two sisters who were unaffected had inherited the same maternal X chromosome (i.e., M2). Two of the daughters who manifested with CSNB had inherited the other maternal X chromosome (M1). The third manifesting sister inherited a recombinant X chromosome with a crossover between TIMP and DXS255, which suggests that the CSNB1 locus lies proximal to TIMP. One of the affected daughters' sons had inherited the maternal M1 X chromosome, a finding consistent with that chromosome carrying a mutant CSNB gene; the other affected sons inherited the grandfather's X chromosome (i.e., P). Molecular analysis of DNA from three sisters with manifestations of CSNB is consistent with their being homozygous at the CSNB1 locus and with their mother being a carrier of CSNB1. PMID- 8434608 TI - Detection of a molecular deletion at the DXS732 locus in a patient with X-linked hypohidrotic ectodermal dysplasia (EDA), with the identification of a unique junctional fragment. AB - X-linked hypohidrotic ectodermal dysplasia (EDA) has been localized to the Xq12 q13.1 region. A panel of genomic DNA samples from 80 unrelated males with EDA has been screened for deletions at seven genetic loci within the Xq12-13 region. A single individual was identified with a deletion at the DXS732 locus by hybridization with the mouse genomic probe pcos169E/4. This highly conserved DNA probe is from locus DXCrc169, which is tightly linked to the Ta locus, the putative mouse homologue of EDA. The proband had the classical phenotype of EDA, with no other phenotypic abnormalities, and a normal cytogenetic analysis. A human genomic DNA clone, homologous to pcos169E/4, was isolated from a human X chromosome cosmid library. On hybridization with the cosmid, the proband was found to be only partially deleted at the DXS732 locus, with a unique junctional fragment identified in the proband and in three of his maternal relatives. This is the first determination of carrier status for EDA in females, by direct mutation analysis. Failure to detect deletion of the other loci tested in the proband suggests that the DXS732 locus is the closest known locus to the EDA gene. Since the DXS732 locus contains a highly conserved sequence, it must be considered to be a candidate locus for the EDA gene itself. PMID- 8434609 TI - Uniparental disomy for chromosome 16 in humans. AB - The association between chromosomal mosaicism observed on chorionic villus sampling (CVS) and poor pregnancy outcome has been well documented. CVS mosaicism usually represents abnormal cell lines confined to the placenta and often involves chromosomal trisomy. Such confined placental mosaicism (CPM) may occur when there is complete dichotomy between a trisomic karyotype in the placenta and a normal diploid fetus or when both diploid and trisomic components are present within the placenta. Gestations involving pure or significant trisomy in placental lineages associated with a diploid fetal karyotype probably result from a trisomic zygote which has lost one copy of the trisomic chromosome in the embryonic progenitor cells during cleavage. Uniparental disomy would be expected to occur in one-third of such cases. Trisomy of chromosome 7, 9, 15, or 16 is most common among the gestations with these dichotomic CPMs. Nine pregnancies with trisomy 16 confined to the placenta were prenatally diagnosed. Pregnancy outcome, levels of trisomic cells in term placentas, and fetal uniparental disomy were studied. Intrauterine growth retardation (IUGR), low birthweight, or fetal death was observed in six of these pregnancies and correlated with high levels of trisomic cells in the term placentas. Four of the five cases of IUGR or fetal death showed fetal uniparental disomy for chromosome 16. One of the infants with maternal uniparental disomy 16 had a significant malformation (imperforate anus). All infants with normal intrauterine growth showed term placentas with low levels of trisomic cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8434610 TI - Gaucher disease: gene frequencies in the Ashkenazi Jewish population. AB - DNA from over 2,000 Ashkenazi Jewish subjects has been examined for the four most common Jewish Gaucher disease mutations, which collectively account for about 96% of the disease-producing alleles in Jewish patients. This population survey has made possible the estimation of gene frequencies for these alleles. Eighty-seven of 1,528 individuals were heterozygous for the 1226G (N370S) mutation, and four presumably well persons were homozygous for this mutation. The gene frequency for the 1226G allele was calculated to be .0311, and when these data were pooled with those obtained previously from another 593 Jewish subjects, a gene frequency of .032 with a standard error of .004 was found. Among 2,305 normal subjects, 10 were found to be heterozygous for the 84GG allele, giving a gene frequency of .00217 with a standard error of .00096. No examples of the IVS2(+1) mutation were found among 1,256 samples screened, and no 1448C (L444P) mutations were found among 1,528 samples examined. Examination of the distribution of Gaucher disease gene frequencies in the general population shows that the ratio of 1226G mutations to 84GG mutations is higher than that in the patient population. This is presumed to be due to the fact that homozygotes for the 1226G mutation often have late-onset disease or no significant clinical manifestations at all. To bring the gene frequency in the patient population into conformity with the gene frequency in the general population, nearly two-thirds of persons with a Gaucher disease genotype would be missing from the patient population, presumably because their clinical manifestations were very mild. PMID- 8434611 TI - Localization of juvenile, but not late-infantile, neuronal ceroid lipofuscinosis on chromosome 16. AB - The neuronal ceroid lipofuscinoses (NCL) are a group of progressive neurodegenerative disorders characterized by the deposition of autofluorescent proteinaceous fingerprint or curvilinear bodies. We have found that CLN3, the gene underlying the juvenile form of NCL, is very tightly linked to the dinucleotide repeat marker D16S285 on chromosome 16. Integration of D16S285 into the genetic map of chromosome 16 by using the Centre d'Etude du Polymorphisme Humain panel of reference pedigrees yielded a favored marker order in the CLN3 region of qtel-D16S150-.08-D16S285-.04-D16S148-.02-D16S 67-ptel. The most likely location of the disease gene, near D16S285 in the D16S150-D16S148 interval, was favored by odds of greater than 10(4):1 over the adjacent D16S148-D16S67 interval, which was recently reported as the minimum candidate region. Analysis of D16S285 in pedigrees with late-infantile NCL virtually excluded the CLN3 region, suggesting that these two forms of NCL are genetically distinct. PMID- 8434612 TI - The morquio A syndrome (mucopolysaccharidosis IVA) gene maps to 16q24.3. AB - The gene for N-acetylgalactosamine-6-sulfatase, the deficiency of which results in Morquio A syndrome (mucopolysaccharidosis type IVA), was assigned to chromosome 16 at band q24.3 by fluorescence in situ hybridization. Localization of this band was confirmed by PCR analysis of a somatic cell hybrid panel used for fine mapping of chromosome 16. PMID- 8434614 TI - Long term survival of an infant with sirenomelia. AB - We report on a 3-month-old infant whose sirenomelia was diagnosed prenatally. The infant is neurologically normal and has "fusion" of the lower limbs with associated renal dysplasia, imperforate anus, pelvic and sacral "dysplasia," and genital abnormalities. In addition she has a preauricular skin tag and rib fusion. The infant's anomalies are compatible with life and surgical separation of the lower limbs is planned. PMID- 8434613 TI - Genetic recombination events which position the Friedreich ataxia locus proximal to the D9S15/D9S5 linkage group on chromosome 9q. AB - The absence of recombination between the mutation causing Friedreich ataxia and the two loci which originally assigned the disease locus to chromosome 9 has slowed attempts to isolate and characterize the genetic defect underlying this neurodegenerative disorder. A proximity of less than 1 cM to the linkage group has been proved by the generation of high maximal lod score (Z) to each of the two tightly linked markers D9S15 (Z = 96.69; recombination fraction [theta] = .01) and D9S5 (Z = 98.22; theta = .01). We report here recombination events which indicate that the FRDA locus is located centromeric to the D9S15/D9S5 linkage group, with the most probable order being cen-FRDA-D9S5-D9S15-qter. However, orientation of the markers with respect to the centromere, critical to the positional cloning strategy, remains to be resolved definitively. PMID- 8434615 TI - Pfeiffer syndrome update, clinical subtypes, and guidelines for differential diagnosis. AB - Steven Pfeiffer syndrome pedigrees (three 3 generation and four 2 generation) have been recorded to date in addition to at least a dozen sporadic cases. Autosomal dominant inheritance with complete penetrance is characteristic of the 7 familial instances. Variable expressivity has involved mostly the presence or absence of syndactyly and the degree of syndactyly when present. Classic Pfeiffer syndrome is designated type I. Type 2 consists of cloverleaf skull with Pfeiffer hands and feet together with ankylosis of the elbows. Such patients do poorly with an early death. All reported instances to date have been sporadic. Type 3 is similar to type 2 but without cloverleaf skull. Ocular proptosis is severe in degree and the anterior cranial base is markedly short. These patients also do poorly and tend to have an early death. To date all cases have occurred sporadically. Although these 3 clinical subtypes do not have status as separate entities, their diagnostic and prognostic implications are important. Type 1 is commonly associated with normal intelligence, generally good outcome, and can be found dominantly inherited in some families. Types 2 and 3 generally have severe neurological compromise, poor prognosis, early death, and sporadic occurrence. Recognition of type 3 is particularly important because extreme ocular proptosis in the absence of cloverleaf skull but with various visceral anomalies can result in failure to diagnose Pfeiffer syndrome and labeling the patient as an "unknown" or as a "newly recognized entity."(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8434616 TI - Confirmation that the velo-cardio-facial syndrome is associated with haplo insufficiency of genes at chromosome 22q11. AB - The velo-cardio-facial syndrome (VCFS) and DiGeorge sequence (DGS) have many similar phenotypic characteristics, suggesting that in some cases they share a common cause. DGS is known to be associated with monosomy for a region of chromosome 22q11, and DNA probes have been shown to detect these deletions even in patients with apparently normal chromosomes. Twelve patients with VCFS were examined and monosomy for a region of 22q11 was found in all patients. The DNA probes used in this study could not distinguish the VCFS locus and the DGS locus, indicating that the genes involved in these haploinsufficiencies are closely linked, and may be identical. The phenotypic variation of expression in VCFS and DGS may indicate that patients without the full spectrum of VCFS abnormalities but with some manifestations of the disorder may also have 22q11 deletions. PMID- 8434617 TI - Velo-cardio-facial syndrome: a review of 120 patients. AB - A series of earlier reports has described the velo-cardio-facial syndrome (VCFS), a syndrome of multiple anomalies including cleft palate, heart malformations, facial characteristics, and learning disabilities. The patients reported previously were primarily ascertained from a craniofacial program at a large tertiary medical center. Recent reports, including a companion paper in this issue, suggest that this common syndrome of clefting is also a common syndrome of congenital heart defect (CHD) which is expressed as familial examples of DiGeorge sequence. Appreciation of more severely affected cases of VCFS and the detection of mild expressions have led to a broadening of the phenotypic spectrum of the syndrome. The purpose of this report is to describe the full spectrum of VCFS, including several new manifestations and to compare the VCFS phenotype with published cases of "familial DiGeorge sequence" which are now thought to represent examples of VCFS. PMID- 8434618 TI - Spondylo-meta-epiphyseal dysplasia (SMED), short limb-hand type: a congenital familial skeletal dysplasia with distinctive features and histopathology. AB - We report on a "new" severe short-limb bone dysplasia which can be labeled descriptively a spondylo-meta-epiphyseal dysplasia. The 3 patients were born to 2 unrelated Sepharadic Jewish families and a Puerto Rican family. Clinical abnormalities include small stature with short limbs including short hands, a short nose with wide nasal bridge and wide nostrils, a long philtrum, ocular hypertelorism, retro/micrognathia, and a narrow chest. Radiological abnormalities include platyspondyly, short tubular bones with very abnormal metaphyses and epiphyses beyond early infancy, short ribs, and a typical evolution of bony changes over time. Chondroosseous morphology and ultrastructure document sparse matrix and degenerating chondrocytes surrounded by dense amorphous material in the 1 patient studied. Consanguinity is present in 1 family. In addition to the described patient, 2 other short-limb sibs, who did not survive infancy, were born into this family. Even in the absence of any photographic or radiologic documentation of these other 2 infants, autosomal recessive mode of inheritance seems probable. PMID- 8434619 TI - Barth syndrome: clinical features and confirmation of gene localisation to distal Xq28. AB - Barth syndrome is an X-linked disorder characterised by cardioskeletal myopathy of variable severity usually fatal in childhood, and neutropenia. We ascertained a large pedigree with affected males in 3 generations. All affected males had dilated cardiomyopathy, with endocardial fibroelastosis (EFE) in some. The locus for Barth syndrome in this family was found to be closely linked to DXS52 (z = 2.78, theta = 0.0). The family was nonrecombinant for DXS52 in distal Xq28, but recombinant for DXS374 which maps proximal to DXS52. This localised Barth syndrome distal to DXS374, confirming a previous localisation to distal Xq28. As yet there is no evidence for genetic heterogeneity of Barth syndrome. PMID- 8434621 TI - Familial Mediterranean fever in the colchicine era: the fate of one family. AB - In order to demonstrate the effect of prophylactic colchicine treatment on the natural history of familial Mediterranean fever (FMF), a family is presented with 6 out of 9 siblings affected by FMF. Each patient represents a different stage of the amyloidotic kidney disease of FMF and the effect of continuous colchicine treatment on its course. Considered together, the members of this family present an almost complete clinical, genetic, and behavioral picture of the disease. PMID- 8434620 TI - Trimethylaminuria in a girl with Prader-Willi syndrome and del(15)(q11q13). AB - We report on an individual with trimethylaminuria, Prader-Willi syndrome, and del(15) (q11q13). To our knowledge, such an association has never been reported. Skin sores secondary to choline-rich foods and amenable to dietary control have not been described in trimethylaminuria, although they are seen in some patients with Prader-Willi syndrome. Pathogenesis, clinical diagnosis, and management of reported cases with trimethylaminuria are reviewed. Serious social and behavioral problems may result from strong body odor. Amelioration of the "fish odor" by dietary choline restriction makes trimethylaminuria detection important. Association of trimethylaminuria with Prader-Willi syndrome and del(15) (q11q13) in this patient is of particular interest. It may represent a contiguous gene syndrome, or deletion of the normal allele leading to expression of a single recessive trimethylaminuria gene, or an unrelated association, such as in Noonan syndrome. However, recent development of mapping of flavin-containing monooxygenase 2 (FMO2), the likely enzyme that is defective in fish odor syndrome, to chromosome 1q probably excludes pathogenetic association of fish odor syndrome with the Prader-Willi syndrome. PMID- 8434622 TI - Microcephaly and digital anomalies: a newly recognized syndrome of recessively inherited mental retardation. AB - We describe 2 brothers with congenital microcephaly and moderately severe mental retardation. The presence of identical and symmetrical digital anomalies suggests that this constellation represents a clinically recognizable recessively inherited mental retardation syndrome. Recognition of the clinical diagnosis should provide accurate genetic counseling to parents of a single affected child. PMID- 8434623 TI - Elevated human chorionic gonadotropin levels in pregnancies with sex chromosome abnormalities. AB - Numerous reports have dealt with the usefulness of the maternal serum alpha fetoprotein marker (MsAFP) and human chorionic gonadotropin (MshCG) levels in the detection of Down syndrome (DS) and other autosomal trisomies. Only few reports have discussed the possible association of elevated levels of MshCG and sex chromosome aneuploidy. We wish to report on 3 cases in which this association was found. PMID- 8434624 TI - Syndrome of cleft palate, microcephaly, large ears, and short stature (Say syndrome). AB - In 1975 Say et al. (Humangenetik 26:267-269) reported on a new dominantly inherited syndrome of cleft palate, short stature, microcephaly, large ears, and hand anomalies in 4 members of a family. This is a report of a 13-month-old girl with cleft palate, short stature, microcephaly, sparse scalp hair, large abnormally shaped ears, small hands with tapering fingers, delayed bone age, unusual dermatoglyphics, proximal renal tubular acidosis with cystic dysplasia of the kidneys, and developmental delay. This case appears to be the second report of this syndrome which presumably occurred as a new mutation in this family. PMID- 8434625 TI - Unbalanced mosaic karyotypes with different structural abnormalities involving a common chromosome region: report of two cases. AB - We report on 2 cases with different de novo unbalanced mosaic karyotypes in which each cell line had a different structural abnormality involving a common chromosome region: 46,XX,del(11)(q23.3)/46,XX.-11, + der(11)t(11;?)(q23.3;?) and 46,X,idic(Xq)/46,X,idic(Xq),-12, + der(12)t(X;12)(p11.2;p13.3). Molecular cytogenetic analysis confirmed the origin of the derivative 12 chromosome in the latter. We present a literature review of reports with mosaic cell lines of structural chromosome abnormalities that share the same chromosome breakpoint. PMID- 8434626 TI - Michelin tire baby syndrome: familial constriction bands during infancy and early childhood in four generations. AB - We report on an infant with an unusual pattern of transitory familial constriction bands distributed symmetrically and circumferentially over the neck, forearms, and lower legs. Family history showed the occurrence of similar bands among individuals in 4 generations transmitted as an autosomal dominant trait. Neck and limb distribution in the other affected family members was also symmetrical and circumferential, with spontaneous resolution taking place during childhood. This case represents another example of the Michelin tire baby syndrome, also known as multiple benign circumferential skin creases of the limbs, and further demonstrates its autosomal dominant mode of inheritance. PMID- 8434627 TI - Extended major histocompatibility complex haplotypes in celiac patients in the west of Ireland. AB - The highest reported prevalence of celiac disease (gluten-sensitive enteropathy) is found in the West of Ireland. Recent genetic data have suggested that major histocompatibility complex-linked loci may have a dominant genetic effect for disease susceptibility in this population compared with a recessive effect in other groups. To further understand the role of the MHC in celiac disease in the West of Ireland, we analyzed markers for 22 MHC haplotypes from celiac patients and compared them with 18 nontransmitted haplotypes found in the parents of celiac children, and with reported haplotypes from other populations. An extended MHC haplotype including [HLA-B8, DR3, DQw2, Bf*S, C4A*Q0, and C4B*1] accounted for 50% of celiac haplotypes but only 27% of nontransmitted parental haplotypes. Compared with other reported haplotypes in celiacs, patients from the West of Ireland show a higher prevalence of HLA-A1 as a component of this extended haplotype, suggesting that although the core haplotype is similar between Irish patients and others, the celiac population in the West of Ireland differs at other HLA loci. We did not observe any other common haplotypes among our patients unlike the situation in other populations. These differences may underlie the possible dominant effect of HLA-linked loci and the unusually high prevalence of celiac disease in the Irish population. We also found that the serum levels of complement components C3c, C4, and factor B were significantly lower among celiac patients than nonceliacs. The lower serum level of C4 appears to be related to the presence of deletions and null alleles at the C4A and C4B loci in celiacs. PMID- 8434628 TI - Prenatal diagnosis of tetraploidy: a case report. AB - We report on the second trimester prenatal diagnosis of an apparently nonmosaic tetraploid fetus, 92,XXYY. Indications for cytogenetic studies of the fetus included abnormal ultrasound findings and abnormal maternal serum levels of alpha fetoprotein (AFP)/estriol. Chromosome analysis of amniocytes documented tetraploidy, a finding confirmed by flow cytometry of several fetal tissues. Autopsy findings in the fetus are compared with those of other cases of tetraploidy. To our knowledge this is the first reported prenatal diagnosis of a tetraploid fetus. Additionally, it illustrates the value of flow cytometric analysis of products of conception in which polyploidy is suspected. PMID- 8434629 TI - Angular homeostasis. IX. Polygonal orbits with a moving target: implications for anomalous numbers of digits in congenital heart disease. AB - This paper explores properties of discrete processes in which a pursuer seeks a target that is moving at constant velocity r that is a fixed proportion of the speed of the pursuer. The pursuer is subjected to proportional angular homeostasis, so chosen that the number of steps per circuit is small. The orbits relative to the target may assume any of four forms: polygons that reverse their sense an infinite number of times; or polygons that after a finite number of reversals ultimately come to have an integer numbers of sides; or have a rational numbers of sides; or have an irrational number of sides that densely fill an annulus. None of the polygons is regular. In the parameter space, the boundary line between the first of these sets and the other three has a somewhat bizarre pattern and may possibly be fractal, but no proof is forthcoming. Unlike the pattern with a stationary target, there may be a set or catchment of diverse values of the speed ratio, r, and the correction coefficient, b that all result in figures of some specified number, n, of sides (although with vertices in differing locations). Catchments have been found for only those polygons that have the winding number of 1. The implications are discussed that this property has for the genetic coding of biological traits that are countable. Some attention is also paid to the relevance of polygons with few sides to ontogenic growth when the correction coefficient is cyclically arc- or time-dependent. PMID- 8434630 TI - Birth prevalence study of the Apert syndrome. PMID- 8434631 TI - Ankyloblepharon filiforme adnatum and imperforate anus. PMID- 8434632 TI - Prolonged maternal diet imbalance and recurrent fetuses with congenital anomalies. PMID- 8434633 TI - Decrease in the size of the myotonic dystrophy CTG repeat during transmission from parent to child: implications for genetic counselling and genetic anticipation. AB - Recently an unstable trinucleotide CTG repeat, located within the 3' untranslated region of a gene on 19q13.3 was discovered in kindreds with myotonic dystrophy (DM). The age-of-onset/severity of DM shows a good correlation with CTG repeat size, and pedigrees and data reported to date have shown a striking trend toward amplification of the size of the CTG repeat during transmission from parent to child. The amplification has been accepted as the biological explanation for anticipation in the clinical severity observed in many families with DM. In this paper we report on 3 families where CTG amplification decreased during transmission from parent to child. In one case there was a gene conversion event, while in the remaining 2 there was a simpler reduction in the size of the repeat length. The changes appear to have been accompanied by a reduction in clinical severity in the child when compared to the parent. These observations are discussed in terms of their clinical implications and the biases that may exist in much of the reported data. PMID- 8434634 TI - Presymptomatic diagnosis of SMA III by genotype analysis. AB - Linkage analysis and prenatal prediction in families segregating autosomal recessive spinal muscular atrophy (SMA) has become feasible since the assignment of the locus responsible for type I-III SMA to region 5q12-q13.3. We have performed a segregation study of SMA in Italian families using molecular probes and highly informative PCR-based polymorphic markers. In one family, a 7-year-old boy affected with type III SMA and an 8-year-old apparently healthy brother had identical haplotypes. These findings prompted us to reexamine the apparently unaffected child. His neurological exam was normal. However, the electromyography (EMG) showed a pattern consistent with chronic SMA. To our knowledge this is the first example of presymptomatic diagnosis of SMA based on genotype analysis. PMID- 8434635 TI - Registry of Experimental Cancers of the National Cancer Institute. A database resource for cancer research. AB - The National Cancer Institute established the Registry of Experimental Cancers in March 1970. This registry consists of a permanent collection of pathological materials on spontaneous and induced lesions in laboratory animals that includes histological slides, paraffin blocks, autopsy findings, pathological diagnoses, photographs, and experimental records. The material presently is composed of approximately 60,000 consecutive records and is a valuable resource for researchers interested in tumors and other lesions arising spontaneously or from specific induction protocols in experimental animals. The entire registry database was transferred to an object-oriented database that permits registry staff to write programs for the different data field objects, thus customizing searches and other database functions. Twenty-seven animal species are represented and a total of 6,496 diagnostic entities and 1,106 treatment and control protocols are listed. Archival material may be retrieved for analysis of molecular markers. PMID- 8434636 TI - Messenger RNA for two type IV collagenases is located in stromal cells in human colon cancer. AB - The gene expression of two type IV collagen-degrading enzymes (72-kd and 92-kd type IV collagenases) was investigated in human colon adenocarcinomas by in situ hybridization. In all cases (18 out of 18), messenger RNA for the 72-kd type IV collagenase was present and located in numerous fibroblasts in the stroma surrounding the invasive cancer tissue. In normal-appearing colonic mucosa distant from the cancer tissue, either no expression or only very weak expression of this enzyme was detected. Also the 92-kd type IV collagenase was found in all samples investigated (10 out of 10), exclusively expressed by tissue macrophages. A very strong hybridization signal for messenger RNA for the 92-kd enzyme was found in a subpopulation of tissue macrophages surrounding invading malignant epithelium. In normal-appearing colon tissue, a markedly weaker hybridization signal was observed in macrophages contained in Peyer's patches. No hybridization signals for either of the two type IV collagenases were detected in cancer cells. Together with previous findings on expression of components of the plasminogen activation system, these results indicate that several nonepithelial cell types in the tumor stroma are involved in production of factors involved in extracellular proteolysis during colon cancer invasion. PMID- 8434637 TI - Detection of p53 overexpression in routinely paraffin-embedded tissue of human carcinomas using a novel target unmasking fluid. AB - With the aid of a newly developed target unmasking fluid (TUF), p53 overexpression was visualized by immunohistochemistry on recent and archival paraffin-embedded tissue samples of colon, stomach, and pancreas neoplasms. Using monoclonal anti-p53 antibody pAb1801 as well as polyclonal antiserum to p53 CM1, TUF-mediated immunohistochemistry was fully concordant for p53 overexpression in paraffin-embedded carcinoma samples compared with freshly frozen tissue from the same tumors. Thus, prognostic and diagnostic assessment of p53 overexpression in malignant tissue, routinely fixed in formalin and embedded in paraffin wax, by TUF-mediated immunohistochemistry with monoclonal and polyclonal antibodies may be adopted as a new tool in diagnostic and research histopathology. PMID- 8434638 TI - bcl-2 rearrangement in Hodgkin's disease. Results of polymerase chain reaction, flow cytometry, and sequencing on formalin-fixed, paraffin-embedded tissue. AB - We examined 81 cases of Hodgkin's disease for evidence of the t(14;18) translocation, using the polymerase chain reaction assay on lysates of formalin fixed, paraffin-embedded tissue. Seven of 74 amplifiable cases (9%) were positive for the translocation, which involves the bcl-2 oncogene and the immunoglobulin heavy chain gene. Two of these cases were sequenced and the breakpoints had the same pattern found in follicular lymphoma. The nuclei from one of the cases were sorted into large and small subpopulations. The t(14;18) signal was more intense in the large nucleus subpopulation, which contained a greater proportion of Reed Sternberg-like nuclei. These results are consistent with the hypothesis that Reed Sternberg cells carry the translocation, but they do not exclude the possibility that the translocation is found in cells representing the reactive component of Hodgkin's disease. The results also demonstrate that routinely processed material is suitable for polymerase chain reaction-based analysis of translocations, although the sensitivity is reduced 10- to 100-fold, compared with fresh tissue. PMID- 8434639 TI - A retinoid responsive cytokine gene, MK, is preferentially expressed in the proximal tubules of the kidney and human tumor cell lines. AB - The aim of this study was to survey the expression of an embryonic cytokine gene, MK, in the normal organs and neoplastic tissues of adults. Northern analysis showed that MK mRNA was exclusively expressed in the kidney among murine organs including thymus, lung, heart, spleen, liver, and kidney. In situ hybridization analysis revealed that MK expression was localized in the proximal tubules and metaplastic Bowman's epithelium, but not in other nephron segments such as glomeruli, loop of Henle, distal tubules, and collecting ducts. To investigate whether MK expression is a marker of tubular cell lineage, several cell lines originating from renal tubules were tested. No expression of MK was detected in PtK1 and LLC-PK1 cells derived from marsupial and porcine proximal tubules or in MDBK and MDCK cells from bovine and canine distal/collecting tubules. Unexpectedly, the MK gene was expressed in a human renal cell carcinoma line, VMRC-RCW, and the expression was up-regulated in the presence of retinoic acid. To elucidate the involvement of MK in the development of tumors, we further examined its expression in a variety of human neoplastic cell lines: YMB-1-C (breast cancer), EBC-1 (lung squamous cell carcinoma), RERF-LC-OK (lung adenocarcinoma), SBC-3 (lung small cell carcinoma), HSC-2 (mouth squamous cell carcinoma), NUGC-2 (gastric cancer), COLO201 (colon cancer), HepG2 (hepatoma), MIA PaCa-2 (pancreatic cancer), MCAS (ovarian cancer), HeLa (cervical cancer), BeWo (chorionic carcinoma), ITO-II (testicular tumor), T24 (urinary bladder tumor), and G-401 (Wilms' tumor). Strong signals were detected in COLO201, HepG2, ITO-II, T24, G-401, and weaker but distinct signals were detected in YMB-1-C, HSC 2, and MCAS cells. The MK gene was, therefore, widely expressed in neoplastic cells originating from genital organs, intestinal tract, liver, mammary gland, and urinary tract, and the expression was not restricted to adenocarcinomas, but was also observed in other types of tumor cells. These findings suggest that a retinoic acid responsive gene, MK, may play a role in the pathophysiology of renal proximal tubules and tumorigenesis in many types of neoplasms. PMID- 8434640 TI - Expression of IP-10, a lipopolysaccharide- and interferon-gamma-inducible protein, in murine mesangial cells in culture. AB - IP-10 is an early gene induced in multiple cell types by a variety of proinflammatory agents, notably interferons (IFNs) and lipopolysaccharide (LPS). To determine whether this protein might play a role in amplifying immune-mediated glomerular injury, we cultured mouse mesangial cells with several stimuli for various times. Increasing amounts of IFN-gamma (to 100 units/ml) elicited increasing levels of IP-10 messenger RNA (mRNA), sustained to 24 hours, but had no effect on tumor necrosis factor-alpha (TNF-alpha) mRNA. LPS induced transient IP-10 mRNA expression that peaked at 8 hours; TNF-alpha mRNA was also increased. TNF-alpha at doses up to 10 ng/ml and soluble immune complexes up to 150 micrograms/ml antibody evoked 3- to 5-fold increases in IP-10 mRNA expression, much less than the 30- to 70-fold increases seen with IFN-gamma and LPS. We conclude that IFN-gamma, LPS, and other agonists can amplify glomerular immune injury, perhaps via elevated expression of IP-10. PMID- 8434641 TI - Phagocytosis of latex beads is defective in cultured human retinal pigment epithelial cells with persistent rubella virus infection. AB - Phagocytosis, a secondary function of retinal pigment epithelial (RPE) cells essential to sight, was significantly decreased, when measured with latex beads, during persistent rubella virus (RV) infection of human cultured RPE cells. A target for RV in vivo, RPE cells infected with RV (RPE/RV) ingested fewer fluorescent microspheres (26%) than did uninfected RPE cells (68%) (P < 0.001), as measured by flow cytometry. In RPE/RV cells, with characteristic RPE monolayer appearance and normal growth during subculturing over 6 months, persistent RV infection was shown by specific RV antigen immunofluorescence, by the presence of the RV genome in RPE/RV cell messenger RNA, and by recovery of cell-free RV after cocultivation with Vero cells. The adhesion of latex beads to apical cell surfaces of RPE/RV and uninfected RPE cells appeared similar, as imaged by scanning electron microscopy. Cytoskeletal actin, a component of phagocytosis in RPE, appeared altered in 60 to 75% of RPE/RV cells by antiactin immunofluorescence staining, as previously described in other RV-infected cells, but its role in the disturbed phagocytosis of latex beads was not determined. Persistently RV-infected human RPE is an additional example of RV-associated secondary cellular dysfunction in the absence of cytopathic effects. PMID- 8434642 TI - Role of platelet-activating factor in polymorphonuclear neutrophil recruitment in reperfused ischemic rabbit heart. AB - This study investigated the role of platelet-activating factor in the recruitment of polymorphonuclear neutrophils (PMN) in a rabbit model of cardiac ischemia and reperfusion. The accumulation of PMN was evaluated 2 and 24 hours after removal of 40 minutes of coronary occlusion by morphometric analysis and 111In-labeled PMN infiltration. The administration of two structurally unrelated platelet activating factor-receptor antagonists (SDZ 63-675, 5 mg/kg body weight, and WEB 2170, 5 mg/kg body weight) before reperfusion significantly reduced the accumulation of PMN, as well as the hemodynamic alterations and the size of necrotic area. Two hours after reperfusion, the percentage of increase of 111In labeled PMN in transmural central ischemic zone was significantly reduced in rabbits pretreated with SDZ 63-675 (51.4 +/- 7.9) or WEB 2170 (32.4 +/- 8.8) with respect to untreated rabbits (107.6 +/- 13.5). The morphometric analysis of myocardial sections confirmed the reduction of PMN infiltration at 2 hours and demonstrated that at 24 hours the phenomenon was even more significant. In addition, SDZ 63-675 and WEB 2170 prevented early transient bradycardia and hypotension and reduced the infarct size, judged by staining with tetrazolium at 2 and 24 hours after reperfusion, and by histological examination at 24 hours. These results suggest that platelet-activating factor is involved in the accumulation of PMN in the reperfused ischemic myocardium and contributes to the evolution of myocardial injury. PMID- 8434643 TI - Expression patterns of leukocyte adhesion ligand molecules on human liver endothelia. Lack of ELAM-1 and CD62 inducibility on sinusoidal endothelia and distinct distribution of VCAM-1, ICAM-1, ICAM-2, and LFA-3. AB - Vascular expressed adhesion molecules mediate leukocyte reactivity and activation by receptor-ligand binding. A number of different ligand molecules have been identified to mediate the interaction between endothelial cells and leukocyte subpopulations. In this study, the tissue expression of ELAM-1, CD62 (PADGEM, GMP 140), VACM-1 (INCAM-110), ICAM-2, ICAM-1, and LFA-3 was analyzed on various liver endothelial cell types by immunohistology. The results reveal a differential expression of these molecules in normal liver and inflammation or rejection after liver transplantation. The selectins ELAM-1 and CD62 are basally expressed and inducible on portal tract endothelia (arterial and venous) and central vein endothelia with acute and chronic liver inflammation. Sinusoidal endothelia, however, lack this mechanism, even with severe inflammation, as in cases of irreversible rejection and sepsis. Portal and sinusoidal endothelia show a different expression and inducibility of VCAM-1, ICAM-1, ICAM-2, and LFA-3. The differences in expression of adhesion molecules on liver endothelial cell types may reflect their ability to regulate leukocyte trafficking and activation by means of the expression of specific ligand molecules. The inability of sinusoidal endothelia to express selectins may have implications for the pathophysiology of liver graft infiltration. PMID- 8434644 TI - Shope papilloma cell and leukocyte proliferation in regressing and progressing lesions. AB - Lesions generated by infection with cottontail rabbit papillomavirus frequently undergo spontaneous regression. The purpose of this immunohistochemical study was to compare leukocyte and papilloma cell proliferation in progressing and regressing papillomas and to test the hypothesis that regression was associated with an inhibition of papilloma cell proliferation. The monoclonal antibodies (MAbs) MAb-019 (specific for DNA/bromodeoxyuridine [BrdU] complexes), Ki-67 (specific for actively proliferating cells), L11/135 (specific for rabbit T cells), and 2C4 (specific for rabbit class II antigen) were used for this purpose. In progressing papillomas, there were few leukocytes (< 1%) in the dermis that stained with MAb-019 and Ki-67, whereas these antibodies stained 4.5% and 6.8% of the intraepidermal leukocytes, respectively. Regressing papillomas contained conspicuous leukocytic infiltrates in the dermis, of which 76.9% were L11/135-positive T cells. However, few intradermal leukocytes (< 3%) stained positively with MAb-019 and Ki-67 MAbs, despite expressing rabbit class II antigen. The epidermis of regressing papillomas contained a higher percentage of MAb-019- and Ki-67-positive leukocytes than the epidermis of progressing papillomas. Intraepidermal leukocytes in progressing and regressing papillomas consisted mainly of T cells stained by L11/135. It appeared that many dermal leukocytes (mainly T cells) form a non-cycling T cell population in both progressing and regressing papillomas, whereas intraepidermal T cells in regressing papillomas were effectively activated and represented a cycling T cell population. MAb-019 and Ki-67 MAbs demonstrated similar staining patterns in papilloma and normal tissues. However, in both progressing and regressing papillomas, the Ki-67 MAb usually stained a larger percentage of cells than the MAb-019 MAb. MAb-019 and Ki-67 MAbs showed a homogeneous distribution of positive cells from basal layer to the upper layer in progressing papillomas. On the other hand, in regressing papillomas, cell staining with the two antibodies was concentrated in the basal and lower layers, but not in the upper layers. This result indicates that cell proliferation in the upper epidermal layers is suppressed in regressing papillomas. Our present data show that intraepidermal T- cell activation and suppression of tumor proliferation might play a crucial role in papilloma regression. PMID- 8434645 TI - Cultured rat mesangial cells contain smooth muscle alpha-actin not found in vivo. AB - A monoclonal antibody against smooth muscle alpha-actin (SM alpha-actin) was used to study the expression of SM alpha-actin in kidney sections and mesangial cell (MC) cultures. In the tissue sections, indirect immunofluorescence revealed intense labeling of vascular smooth muscle cells and precapillary pericytes for SM alpha-actin. Glomerular cells including MC were negative, with the exception of scattered smooth muscle cells in the wall of the intraglomerular segment of the efferent arteriole. In contrast, in MC cultures 50 to 95% of the cells displayed bright fluorescence. Immunoreactivity for SM alpha-actin first appeared 3 days after explanation of glomeruli and increased until the primary culture reached subconfluence. In each subculture (1 to 10) expression of SM alpha-actin was weak on day 1 and pronounced at subconfluence. Growth arrest of subconfluent cultures for 1 to 7 days in serum-free medium did not alter the percentage of cells positive for SM alpha-actin. However, exposure of MC to serum-free medium beginning on the first day of subculture curtailed expression of SM alpha-actin. Double-labeling with antibodies against proliferating cell nuclear antigen and SM alpha-actin revealed SM alpha-actin-positive filaments in both replicating and resting cells. In summary, our results demonstrate that some process or processes associated with cell proliferation and cell growth of MC are accompanied by de novo expression of SM alpha-actin. The relevance to the contractile behavior of the difference in SM alpha-actin expression under in vitro and in vivo conditions is unknown. PMID- 8434646 TI - In vivo responses of macrophages and perisinusoidal cells to cholestatic liver injury. AB - We investigated the response of macrophages and perisinusoidal (Ito) cells (PSCs) during the development of secondary biliary cirrhosis after ligation and division of the common bile duct. Liver tissue was obtained from three groups of male Wistar rats: 1) untreated controls (n = 3); 2) common bile duct-ligated (CBDL) animals (n = 15); and 3) sham-operated controls (n = 15). Material from animal groups 2 and 3 was obtained on days 3, 7, 14, 21, and 28 after operation; in all animals 5-bromo-2-deoxyuridine was administered intraperitoneally before death. Monocytes and macrophages were detected using the monoclonal antibody ED1 and tissue macrophages using the antibody ED2. Cell proliferation within the macrophage population was demonstrated by double labeling for ED2 and incorporated 5-bromo-2-deoxyuridine. PSCs were demonstrated in tissue sections by immunolocalization of desmin; proliferating PSCs were identified by double labeling for desmin and incorporated 5-bromo-2-deoxyuridine. Evidence of phenotypic modulation of PSCs was sought using anti-alpha-smooth muscle actin (alpha-SMA) antibody. Increased numbers of ED1- and ED2-positive cells were seen in CBDL animals at all time points. Local proliferation of macrophages could be identified and reached a peak at day 3, thereafter falling toward control values. Compared with those of controls, livers of CBDL animals showed increased numbers of desmin-positive PSCs in periportal zones from day 3 on, reaching a peak at day 14 (127.8 +/- 10.99 cells/0.635 mm2) and followed by a plateau. PSC proliferation peaked at days 3 and 7 (labeling indices 11.2% and 11.2%, respectively) and thereafter fell toward control values; no expansion of the PSC population was seen in sham-operated rats. Increased alpha-SMA-positive cells were also noted from day 3, with a peak at day 21 (231.1 +/- 11.52 cells/0.635 mm2) and followed by a plateau. En face labeling experiments in days 14, 21, and 28 CBDL animals showed cells co-expressing alpha-SMA and desmin and cells expressing alpha-SMA alone. These results indicate that in response to chronic cholestatic liver injury, PSCs proliferate and undergo phenotypic modulation toward "myofibroblast like" cells. The kinetics of the response are similar to those of the ED2 positive cell population in keeping with a hypothesis that PSC proliferation and activation may be mediated by factors released by macrophages in response to various forms of liver injury. We conclude that the responses of macrophages and PSCs to cholestatic injury are similar to those after toxin-induced hepatocyte necrosis. PMID- 8434647 TI - U75412E, a lazaroid, prevents progressive burn ischemia in a rat burn model. AB - Thermal energy causes an immediate, irreversible injury at the burn site, followed by a delayed, reversible tissue loss in the area surrounding the burn site due to progressive ischemia. We investigated the role of lipid peroxidation in the pathogenesis of progressive ischemia in a rat burn model. The burn model consisted of a row of four 10 x 20 mm burns separated by three unburned 5 x 20 mm skin bridges (interspaces). The interspaces became ischemic and necrotic by 24 hours, producing a single wound with the merger of the burn sites. U75412E, a lipid peroxidation inhibitor, preserved vascular patency, restored blood flow, prevented a rise in tissue conjugated dienes, and maintained tissue viability in the interspaces. Four separate burn wounds healed between three viable strips of hair-bearing interspaces. The treatment was effective, when given systemically during the period between 2 hours before and 1 hour after the burn. U75412E prevented progressive burn ischemia and the expansion of tissue loss. PMID- 8434648 TI - Role of mesothelial and submesothelial stromal cells in matrix remodeling following pleural injury. AB - The pleural response to injury is a complex and poorly understood multifactorial process that can result in the development of fibrosis or obliteration of the pleural space. Pleural fibroblasts are considered the main source of extracellular matrix but cell culture studies have demonstrated synthesis of matrix components by mesothelial cells. We assessed the mesothelial cell contribution to extracellular matrix during pleural healing using immunohistochemical technique. Paraffin-embedded tissue of 3 normal adult lungs and 7 adults with active pleuritis were studied using monoclonal antibodies to cytokeratin, type IV collagen, vimentin, and type I procollagen (PCI). Normal pleural had a single layer of cytokeratin-positive and PCI-negative mesothelium over a thin, continuous type IV collagen-positive basement membrane and PCI negative submesothelial stroma. Areas of active pleuritis showed loss of the continuous linear staining with anti-type IV collagen antibody. Coexpression of cytokeratin, vimentin and PCI was identified in spindle and/or cuboidal cells located in the fibrin layer, submesothelial connective tissue layer, or on the pleural surface. These findings suggest that reactive mesothelial cells play an active role in the production of extracellular matrix during pleural injury, and that disruption of the submesothelial basement membrane is a key event in determining subsequent fibrous organization of pleural exudate. PMID- 8434649 TI - Trophoblast and ovarian cancer antigen LK26. Sensitivity and specificity in immunopathology and molecular identification as a folate-binding protein. AB - The LK26 antigen is a cell surface glycoprotein (M(r)35,000 to 40,000) of normal placenta and gestational choriocarcinomas that shows highly restricted distribution in normal tissues, being expressed primarily in a subset of simple epithelia. In this study, immunohistochemical methods were used to examine LK26 expression in 78 ovarian tumors and > 400 tumors of other histological types. Ovarian carcinomas derived from coelomic epithelium showed the most consistent and strongest immunostaining for LK26, with 52 of 56 cases being LK26+. Ovarian tumors of sex cord, germ cell, and stromal origin were generally LK26-. LK26 was not found in normal fetal or adult ovary; however, it was present in the lining epithelia of some benign ovarian cysts. Mesotheliomas, which share a common mesothelial origin with LK26+ ovarian tumors, expressed no or only low levels of LK26. Other epithelial cancers expressed LK26 in subsets of cases and generally showed heterogeneous or weak immunostaining; this group of LK26+ tumors includes endometrial (10 of 11 cases tested), colorectal (six of 27), breast (11 of 53), lung (six of 18), and renal cell (nine of 18) carcinomas. Four of five brain metastases derived from epithelial cancers and three of 21 neuroendocrine carcinomas showed prominent LK26 immunoreactivity. Only rare neuroectodermal tumors (two of 70) and none of the sarcomas (none of 58) or lymphomas tested (none of 21) were LK26+. Tests with cultured cells showed that the LK26 proteins expressed in choriocarcinoma and ovarian cancer cells are biochemically similar, and transfection experiments identified LK26 as an adult-type, high-affinity folate-binding protein. The present study provides the first detailed specificity and sensitivity analysis for folate-binding protein/LK26 in human tumors and defines a role for folate-binding protein/LK26 in immunobiological studies of ovarian cancers and other LK26+ neoplasms. PMID- 8434650 TI - Protein kinase C (PKC) activity and PKC messenger RNAs in human pituitary adenomas. AB - Protein kinase C (PKC) is involved in the differentiation and growth regulation of a variety of tissues including anterior pituitary gland cells. To determine the distribution of PKC in different types of adenomas, PKC activity was analyzed in human pituitary tumors and the effects of hypothalamic hormone stimulation on PKC activity were examined in cultured adenoma cells. Gonadotroph (LH/FSH) and null cell adenomas had significantly higher levels of particulate, soluble, and total PKC activity compared with growth hormone (GH) adenomas (P < 0.05). Chronic stimulation of null cell adenomas with gonadotropin hormone-releasing hormone or of one GH adenoma with GH-releasing hormone for 7 days did not significantly alter total PKC activity in pituitary cells cultured in serum-free medium. Localization of the calcium-dependent PKC isozymes (alpha, beta and gamma) by immunohistochemistry and in situ hybridization revealed predominantly PKC alpha in all adenomas and variable expression of PKC beta and gamma in some tumors. When the calcium-independent PKC isozymes (delta, epsilon, and zeta) were localized by in situ hybridization, normal and neoplastic pituitaries expressed abundant mRNA for PKC epsilon, whereas some tumors and one normal pituitary had a few cells positive for PKC zeta mRNA as evaluated by grain density and the number of cells labeled. These results indicate that there is a variable distribution of PKC mRNA isozymes in human pituitary adenomas and that normal pituitaries and pituitary adenoma cells express the mRNA for both the calcium-dependent and some of the calcium-independent PKC isozymes. Chronic treatment with the hypothalamic gonadotropin hormone-releasing hormone and GH-releasing hormone, which increased LH/FSH and GH secretion, respectively, did not increase PKC activity in cultured adenoma cells. The presence of calcium-dependent and calcium-independent PKC isozymes in normal and neoplastic pituitary cells indicates that PKC probably plays a major role in signal transduction in the human pituitary adenomas examined in this study. PMID- 8434651 TI - Ley specific antibody with potent anti-tumor activity is internalized and degraded in lysosomes. AB - BR96 is a monoclonal antibody (MAb) that recognizes many human carcinomas and can kill antigen-positive tumor cells in vitro. Using both gold and radiolabeled MAb, the distribution and cellular processing of BR96 during cytolysis has been determined. After a brief (< 3 minutes) MAb treatment, cells in suspension are stained by the nuclear viability dye propidium iodide. Whole MAb and F(ab')2 fragments are equally cytotoxic; monovalent F(ab) fragments, however, have no effect on dye uptake unless cross-linked with goat anti-mouse IgG. The level of toxicity is dependent on both MAb dose and on cell surface receptor density. Cell contact may regulate receptor expression. BR96 receptors are more abundant on cells migrating into the open areas of a scratch wounded confluent culture than on the adjacent contact-inhibited cells. BR96 can also inhibit the anchorage independent growth of tumor cells in soft agar showing that its effects on propidium iodide staining are not due to transient changes in membrane permeability. Immunogold electron microscopy reveals that, after a 1-minute treatment, BR96 induces significant infolding of the plasma membrane and that internalized MAb is localized to these structures. Immediately thereafter, large cell surface and intracellular vesicles form, mitochondria are swollen, and membrane integrity is lost. Therefore, BR96 seems to cause morphological changes characteristic of necrosis rather than apoptosis. When bound to adherent carcinoma cells, BR96 is distributed uniformly on the apical surface of cells labeled at 4 C and is enriched at points of cell substratum contact. Upon warming of the cells to 37 C, BR96 localizes in small perinuclear clusters and the cell margin is now devoid of label. Immunogold electron microscopy reveals that BR96 undergoes receptor mediated internalization and is localized within the same coated pits, endosomes, and lysosomes as the transferrin receptor. Quantitative studies using iodinated BR96 show that after 6 hours of chase, a maximum of 53% of the radiolabel is located within the intracellular pool. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicates that 84% of this fraction is nondegraded. BR96 probably cycles between the medium and intracellular pools because the remainder of the radiolabel is in the medium as intact MAb. By 24 hours of chase, the intracellular fraction drops to 30%, while the remaining 70% is present in the culture medium, mostly as low molecular weight degradation products. PMID- 8434652 TI - Progression from ischemic injury to infarct following middle cerebral artery occlusion in the rat. AB - Focal brain ischemia induced in rats by occlusion of an intracranial artery is a widely used paradigm of human brain infarct. Details of the structural changes that develop in either the human or the rat brain at various times after occlusion of an intracranial artery are incompletely characterized. We studied, in 48 adult Wistar rats, structural alterations involving the cerebral hemisphere ipsilateral to an arterial occlusion, at intervals ranging from 30 min to 7 days. Microscopic changes developed over time in separate areas of the corresponding cerebral hemisphere in a predictable pattern, appearing as small lesions in the preoptic area (30 minutes), enlarging to involve the striatum, and finally involving the cerebral cortex. Two types of neuronal responses were noted according to the time elapsed; acute changes (up to 6 hours) included scalloping, shrinkage, and swelling, whereas delayed changes (eosinophilia and karyolysis) appeared later (> or = 12 hours). Three types of astrocytic responses were noted. 1) Cytoplasmic disintegration occurred in the preoptic area at a time and in a place where neurons appeared minimally injured. 2) Nuclear and cytoplasmic swelling were prominent responses in the caudoputamen and cerebral cortex at a time when neurons showed minimal alterations. 3) Increased astrocytic glial fibrillary acidic protein reactivity was noted at the interface between the lesion and the surrounding brain tissue after 4 to 6 hours. The gross pattern of the brain lesion and the maturation of neuronal changes typical of a brain infarct have a predictable progression. Focal brain ischemia of up to 6-hour duration does not induce coagulation necrosis. PMID- 8434654 TI - John Case Nemiah, M.D. Tenth editor, The American Journal of Psychiatry. PMID- 8434653 TI - Visceral glomerular epithelial cells can proliferate in vivo and synthesize platelet-derived growth factor B-chain. AB - In glomerular diseases associated with antibody- and complement-mediated injury to endothelial and mesangial cells, cell proliferation is an important early response that precedes matrix accumulation and glomerulosclerosis. In contrast, in diseases in which the visceral glomerular epithelial cell (vGEC) is the principal target of injury, cell proliferation is not a recognized consequence, although vGECs respond in vitro to a variety of growth factors and inflammatory mediators. To explore the possibility that low levels of vGEC proliferation may occur and participate in such diseases, serial studies were done in the passive Heymann nephritis model of membranous nephropathy, in which the vGEC is the primary target of antibody- and C5b-9-mediated injury. The results showed mitotic figures and positive staining for the proliferating cell nuclear antigen in cells whose location defined them as vGECs. The proliferating cell nuclear antigen positive cells at the edge of the capillary wall were confirmed to be vGECs by double-immunostaining with antibodies to SPARC/osteonectin, which preferentially label vGECs in passive Heymann nephritis. Proliferation of vGECs in vivo was preceded by increased glomerular expression of platelet-derived growth factor (PDGF) B-chain protein and messenger RNA, both of which localized to vGECs. PDGF B-chain protein and messenger RNA were also detected in cultured vGECs. PDGF receptor beta-subunit protein or messenger RNA could not be demonstrated in vGECs in vivo or in vitro, and no growth response of cultured vGECs to PDGF was noted. These results suggest that proliferation of vGECs does occur in a model of glomerular injury induced by antibody and C5b-9 on vGECs. VGEC proliferation and production of PDGF may be involved in the restoration of the capillary wall but could also contribute to local capillary wall injury and proliferation of other cells in Bowman's capsule, interstitium, and tubules. PMID- 8434655 TI - DSM-III and the transformation of American psychiatry: a history. AB - The author traces the history of the development of DSM-III within the larger context--intellectual, economic, scientific, and ideological--of the development of American psychiatry since World War II. Data were obtained through a literature review, investigation of archival material from the DSM-III task force and APA, and interviews with key participants. This research indicates that from the end of World War II until the mid-1970s, a broadly conceived biopsychosocial model, informed by psychoanalysis, sociological thinking, and biological knowledge, was the organizing model for American psychiatry. However, the biopsychosocial model did not clearly demarcate the mentally well from the mentally ill, and this failure led to a crisis in the legitimacy of psychiatry by the 1970s. The publication of DSM-III in 1980 represented an answer to this crisis, as the essential focus of psychiatric knowledge shifted from the clinically-based biopsychosocial model to a research-based medical model. The author concludes that while DSM-III, and the return to descriptive psychiatry which it inaugurated, has had positive consequences for the profession, at the same time it represents a significant narrowing of psychiatry's clinical gaze. PMID- 8434656 TI - Rethinking Oedipus: an evolutionary perspective of incest avoidance. AB - The author presents a biological hypothesis of incest avoidance. Pertinent literature from evolutionary biology, ethology, anthropology, and clinical research is reviewed. Secure early bonding to immediate kin predicts later adaptive kin-directed behaviors, including preferential altruism (kin selection) and incest avoidance. Impaired bonding predicts aberrant kin-directed behavior, including diminished altruism, neglect, and an increased incidence of incest. Failed bonding predicts the highest frequency of incest. Secure bonding to kin may function to establish adaptive kin-directed behaviors, including incest avoidance. Bonding is conceived of as the developmental foundation of a form of social attraction, here called "familial attraction," which is evolutionarily distinct from sexual attraction. PMID- 8434657 TI - Organic mood syndrome associated with detoxification from methadone maintenance. AB - OBJECTIVE: The authors delineate the clinical characteristics of mood state changes that occur in stable opioid-dependent patients undergoing therapeutic detoxification from methadone maintenance treatment. METHOD: Twenty-four patients participated in a blinded protocol for gradual methadone dose reduction that included weekly assessments of affective state using the Profile of Mood States (POMS) as well as weekly assessments of signs and symptoms of opioid withdrawal. Data obtained before methadone dose reduction and during the 2-week period of maximal dysphoric symptoms were compared. Changes in affective and opioid withdrawal measures were compared in patients who differed in their success in completing the detoxification regimen. RESULTS: Sustained increases in POMS scores of greater than 20 points were observed in 12 of the 24 patients during the course of detoxification. The emergence of symptoms of dysphoria was accompanied by insomnia, loss of appetite, and somatic complaints consistent with symptoms of opioid withdrawal but only minimal levels of objective signs of withdrawal. Greater changes from baseline in mood state and opioid withdrawal measures occurred in patients who were unable to complete the detoxification regimen. CONCLUSIONS: The development of an organic mood syndrome is a common occurrence in patients undergoing slow detoxification from methadone maintenance treatment and is associated with a poor outcome. PMID- 8434658 TI - Aging, emotional states, and memory. AB - OBJECTIVE: This study compared the relation between negative mood states and memory in young and elderly subjects. METHOD: Forty-five normal, healthy young volunteers (ages 19-35 years) and 45 normal, healthy elderly volunteers (ages 60 78 years) were administered a verbal list-learning task and self-rated scales of affective states. RESULTS: The elderly group, but not the young group, consistently exhibited significant correlations between their performance on verbal recall measures and their ratings of their anxiety, depression, and withdrawal; i.e., within the elderly group, higher levels of negative affective states were associated with poorer memory. CONCLUSIONS: These findings indicate that aging modulates the relation between emotional state and memory functions, and they are consistent with the hypothesis that the elderly are more vulnerable than the young to the adverse effects of negative emotional states on memory. Therefore, even in normal elderly individuals without diagnosable psychopathology, negative affective states (such as anxiety and depression) may interfere with memory functioning. PMID- 8434659 TI - Schizophrenia-related and affective personality disorder traits in relatives of probands with schizophrenia and personality disorders. AB - OBJECTIVE: The possible heterogeneity of the schizophrenia-related personality disorder traits associated with DSM-III criteria for schizotypal personality disorder was investigated using the family history method. A familial relationship to schizophrenia was hypothesized for schizophrenia-related personality disorder traits without coexisting affective personality disorder traits, pure schizophrenia-related personality disorder traits. Alternatively, a familial relationship with borderline personality disorder was hypothesized for schizophrenia-related personality disorder traits with comorbid affective personality disorder traits. METHOD: Criteria for schizophrenia-related and affective personality disorder traits were used to assess the 588 nonpsychotic first-degree relatives of 55 chronic schizophrenic probands and 67 probands with personality disorders. The probands with one or more DSM-III personality disorders were categorized as having schizotypal personality disorder without borderline personality disorder (pure schizotypal personality disorder), borderline personality disorder without schizotypal personality disorder (pure borderline personality disorder), both disorders, or neither. RESULTS: The morbid risk of all cases of schizophrenia-related personality disorder traits was higher in relatives of probands with schizophrenia and pure schizotypal personality disorder than in relatives of probands with neither schizotypal nor borderline personality disorder; however, it differed only slightly from that observed in the relatives of probands with both schizotypal and borderline personality disorders and pure borderline personality disorder. In contrast, the risk of pure schizophrenia-related personality disorder traits was higher in relatives of probands with schizophrenia and pure schizotypal personality disorder, while the risk of coexisting schizophrenia-related and affective personality disorder traits was lower in both of these groups than among the relatives of probands with both schizotypal and borderline personality disorders and pure borderline personality disorder. CONCLUSIONS: These results offer preliminary indications that schizotypal personality disorder features present without comorbid affective personality disorder traits may more specifically characterize the personality characteristics familially related to schizophrenia. Furthermore, they indicate that schizotypal personality disorder features as currently defined are found in relatives of patients other than those with schizophrenia or schizotypal personality disorder. PMID- 8434660 TI - Depressive symptoms and family history in seasonal and nonseasonal mood disorders. AB - OBJECTIVE: The authors' goal was to compare the symptoms and family history of seasonal affective disorder with those of nonseasonal mood disorders. METHOD: From a subspecialty mood disorders clinic, 34 patients with major depression, seasonal pattern (seasonal affective disorder), diagnosed with DSM-III-R criteria, were matched in age, sex, and diagnostic subtype (recurrent unipolar, bipolar I, or bipolar II) to 34 patients with nonseasonal mood disorders. Data on symptoms during the most recent depressive episode were obtained by chart review and compared by using chi-square tests. Family history data for first-degree relatives of patients with seasonal and nonseasonal mood disorders were gathered by using the family history method, and diagnoses were based on Family History Research Diagnostic Criteria. RESULTS: Patients with seasonal affective disorder reported significantly more hypersomnia, hyperphagia, and weight gain and reported less suicidal ideation and morning worsening of mood than the patients with nonseasonal mood disorders. No differences were found in family histories of mood disorders, other psychiatric disorders, and any psychiatric disorder between the groups with seasonal versus nonseasonal mood disorders. Alcoholism was found more frequently in the relatives of the patients with seasonal affective disorder. CONCLUSIONS: Differences in symptoms between seasonal and nonseasonal mood disorders provide some support for seasonal affective disorder as a diagnostic subtype of mood disorders. However, the genetic loading for mood disorders (of unspecified seasonality), as determined by the family history method, is similar for seasonal and nonseasonal mood disorders. PMID- 8434661 TI - Exclusion of close linkage of Tourette's syndrome to D1 dopamine receptor. AB - OBJECTIVE: The authors' goal was to establish if a mutation in D1 dopamine receptor locus (DRD1), or one genetically close to it, could cause Gilles de la Tourette's syndrome. METHOD: DRD1 and linked markers (D5S36, D5S61, and D5S62) were studied in a large Mennonite Tourette's syndrome kindred. Only individuals with the full Tourette's syndrome were considered to be affected in one series of analyses; in another series the diagnostic spectrum was broadened to include chronic multiple tics. Liability classes were defined to take into account age at onset and sex differences; dominant inheritance was assumed. The authors' version of the LINKMAP program of the LINKAGE package modified to run under distributed parallel processing (Linda LINKMAP) was used for the multipoint linkage analysis. RESULTS: Complete (theta = 0.0) linkage of Tourette's syndrome with DRD1 was ruled out (lod score of -10.1) when the disease was defined narrowly. The area of exclusion of linkage (lod score between -2 and -10.5) extended from map position 0.10 to map position 0.50. The authors conducted an additional (centromeric) multipoint analysis with D5S36 as well as glucocorticoid receptor (GRL) and D5S22, resulting in an overlapping area of exclusion to map position -0.30 when the disease was defined narrowly. CONCLUSIONS: This result provides strong evidence against linkage of the DRD1 D1 dopamine receptor locus with Tourette's syndrome. This exclusion extends the authors' earlier work with the dopamine system in Tourette's syndrome to exclude the two best characterized dopamine receptors from linkage with Tourette's syndrome. PMID- 8434662 TI - Choline acetyltransferase in schizophrenia. AB - OBJECTIVE: To test the hypothesis that schizophrenia involves altered cholinergic tone in the pons, the authors studied post-mortem brain tissue from subjects with schizophrenia. METHOD: The authors used Western immunoblot to measure the concentration of choline acetyltransferase, an acetylcholine synthesizing enzyme, in the post-mortem brain tissue of 25 schizophrenic subjects and 28 nonschizophrenic comparison subjects. They also measured the concentration of glial fibrillary acidic protein, a protein from astrocytes, to examine the question of neurodegeneration. RESULTS: The pontine choline acetyltransferase concentrations of the schizophrenic subjects were 46% lower than those of comparison subjects, a significant difference. Glial fibrillary acidic protein concentrations did not differ between the two groups. CONCLUSIONS: The lower concentration of choline acetyltransferase in the pontine tegmentum of schizophrenic subjects compared with comparison subjects suggests involvement of pontine cholinergic neurons in schizophrenia. PMID- 8434663 TI - Epidemiology of panic disorder in African-Americans. AB - OBJECTIVE: The authors investigated the prevalence and clinical characteristics of panic disorder among African-Americans and whites in a community study. METHOD: A total of 4,287 African-American and 12,142 white subjects were interviewed at five sites as part of the Epidemiologic Catchment Area study. Panic disorder and other diagnoses were made using the National Institute of Mental Health Diagnostic Interview Schedule and DSM-III criteria. RESULTS: The lifetime prevalence of panic disorder was 1.2% among African-Americans and 1.4% among whites, a nonsignificant difference. Comparisons between African-Americans and whites on age at onset, years with panic disorder, and suicide attempts revealed no significant differences. Rates of individual panic symptoms in African-American and white subjects with panic disorder were similar, although African-Americans reported a higher mean number of symptoms during their worst episode. Among subjects with comorbid panic disorder, African-Americans and whites had similar rates of major depression, alcohol abuse, drug abuse, obsessive-compulsive disorder, agoraphobia, somatization disorder, and schizophrenia. Patterns of treatment seeking among African-American and white panic subjects were similar, with the exception that African-Americans were significantly less likely to seek help from a mental health professional in private practice. CONCLUSIONS: On the basis of these findings, the authors conclude that panic disorder in the community is similar among African-Americans and whites with respect to lifetime prevalence, age at onset, years of disorder, symptom distribution, suicide attempts, and comorbidity with other psychiatric disorders. Differences in the diagnosis and treatment of panic disorder by race are not due to differences in the prevalence or nature of the disorder. PMID- 8434664 TI - Premigratory risk factors in Vietnamese Amerasians. AB - OBJECTIVE: The study's goal was to determine the ability of risk factors determined before migration to predict future levels of anxiety and depression in a group of Vietnamese Amerasian immigrants. METHOD: In a cohort of 161 randomly selected Vietnamese Amerasian youth in Vietnam awaiting placement, risk factors for psychological distress were identified with Felsman's 35-item Personal Information Form and the Hopkins Symptom Checklist-25 (HSCL-25). Ninety-five members of the original cohort were subsequently reevaluated, again with the HSCL 25, at a Philippine refugee center during their 6-month stay there awaiting placement in the United States. RESULTS: A statistically significant relationship was found between greater numbers of risk factors identified in Vietnam and higher total symptom levels in the Philippines. The strongest relationship was between greater numbers of risk factors and higher levels of depression. The relationship between number of risk factors and levels of anxiety was not significant. CONCLUSIONS: This study demonstrates the ability of risk factors determined prior to departure in Vietnam to predict future levels of psychological distress in a group of Vietnamese Amerasian immigrants. PMID- 8434665 TI - Dissociative reactions to the San Francisco Bay Area earthquake of 1989. AB - OBJECTIVE: This study systematically evaluated the psychological reactions of a nonclinical population to the October 1989 earthquake in the San Francisco Bay Area. METHOD: A representative group of about 100 graduate students from two different institutions in the Bay Area volunteered to participate in the study. Within 1 week of the earthquake, the authors administered a checklist of anxiety and dissociative symptoms to the subjects, and 4 months later they conducted a follow-up study with the same checklist. RESULTS: The participants reported significantly greater numbers and frequency of dissociative symptoms, including derealization and depersonalization, distortions of time, and alterations in cognition, memory and somatic sensations, during or shortly after the earthquake than after 4 months. To a lesser degree they also reported significantly more nonsomatic anxiety symptoms and Schneider's first-rank symptoms at the earlier testing time. CONCLUSIONS: These results suggest that among nonclinical populations, extreme distress may significantly increase the prevalence and severity of transient dissociative phenomena and anxiety. They provide further evidence of the role that dissociation plays in the response to trauma and are of considerable clinical and theoretical importance in view of the lifetime prevalence of traumatic experiences in the general population. PMID- 8434666 TI - Premilitary MMPI scores as predictors of combat-related PTSD symptoms. AB - OBJECTIVE: The authors used data collected before military service to assess predictors of combat-related lifetime symptoms of posttraumatic stress disorder (PTSD). METHOD: The subjects were 131 male Vietnam and Vietnam-era veterans who had taken the MMPI in college and who were interviewed as adults with the Structured Clinical Interview for DSM-III-R. Scores on the basic MMPI scales were used to predict combat exposure, lifetime history of any PTSD symptoms given exposure, and lifetime PTSD classification (symptoms only, subthreshold PTSD, or full PTSD). RESULTS: Group means on the MMPI scales were within the normal range. No scale predicted combat exposure. Hypochondriasis, psychopathic deviate, masculinity-femininity, and paranoia scales predicted PTSD symptoms. Depression, hypomania, and social introversion predicted diagnostic classification among subjects with PTSD symptoms. The effects persisted when amount of combat exposure was controlled for. CONCLUSIONS: Pre-military personality can affect vulnerability to lifetime PTSD symptoms in men exposed to combat. PMID- 8434667 TI - The course of transient hypochondriasis. AB - OBJECTIVE: This study examined the longitudinal course of patients known to have had a previous episode of transient hypochondriasis. METHOD: Twenty-two transiently hypochondriacal patients and 24 nonhypochondriacal patients from the same general medical clinic were reexamined after an average of 22 months with the use of self-report questionnaires, structured diagnostic interviews, and medical record review. RESULTS: The hypochondriacal patients continued to manifest significantly more hypochondriacal symptoms, more somatization, and more psychopathological symptoms at follow-up. They also reported significantly more amplification of bodily sensations and more functional disability and utilized more medical care. These differences persisted after control for differences in medical morbidity and marital status. Only one hypochondriacal patient, however, had a DSM-III-R diagnosis of hypochondriasis at follow-up. Multivariate analyses revealed that the only significant predictors of hypochondriacal symptoms at follow-up were hypochondriacal symptoms and the tendency to amplify bodily sensations at the baseline evaluation. CONCLUSIONS: Hypochondriacal symptoms appear to have some temporal stability: patients who experienced hypochondriacal episodes at the beginning of the study were significantly more hypochondriacal 2 years later than comparison patients. They were not, however, any more likely to develop DSM-III-R-defined hypochondriasis. Thus, hypochondriacal symptoms may be distinct from the axis I disorder. The data are also compatible with the hypothesis that preexisting amplification of bodily sensations is an important predictor of subsequent hypochondriacal symptoms. PMID- 8434668 TI - Multiple personality disorder in The Netherlands: a clinical investigation of 71 patients. AB - OBJECTIVE: The aim of this study was to describe the phenomenology of multiple personality disorder as presented in a group of Dutch patients. METHOD: Seventy one patients with multiple personality disorder were interviewed with the Dutch version of the Structured Clinical Interview for DSM-III-R Dissociative Disorders (SCID-D); following the SCID-D, the Structured Trauma Interview was administered. Before the interview, patients completed the Dissociative Experiences Scale. RESULTS: The presenting characteristics of the patients showed a striking resemblance to those in several large North American series. Patients had spent an average of 8.2 years in the mental health system prior to correct diagnosis. Patients presented with many different symptoms and frequently received other psychiatric or neurological diagnoses. A history of childhood physical and/or sexual abuse was reported by 94.4% of the subjects, and 80.6% met criteria for posttraumatic stress disorder. CONCLUSIONS: Patients with multiple personality disorder have a stable set of core symptoms throughout North America as well as in Europe. To improve the detection of patients at high risk for multiple personality disorder, standardized instruments for inquiry about dissociative pathology should be used as part of routine diagnostic assessment. PMID- 8434669 TI - Correlation of acute cocaine-induced changes in local cerebral blood flow with subjective effects. AB - The authors administered 48 mg of intravenous cocaine or placebo to eight abstinent cocaine users in a double-blind, crossover design and examined blood flow using single photon emission computed tomography. Cocaine produced significant decreases in frontal cortical and basal ganglia blood flow; these latter correlated negatively with increases in self-ratings of "rush" and "high." The authors conclude that these local effects are compatible with dopaminergic system involvement. PMID- 8434670 TI - A pilot study of assertive community treatment for patients with chronic psychotic disorders. AB - This study measured hospital utilization and residential status of 51 patients with chronic psychoses before and after a 1-year program of assertive community treatment. Time hospitalized was reduced by 94%, and 82% of the patients previously living in hospitals or group homes attained independent living status, suggesting that this form of clinical management may reduce institutional care and costs to mental health care systems. PMID- 8434671 TI - Subclinical hypothyroidism: a modifiable risk factor for depression? AB - The authors assessed the lifetime history of major depression in 16 subjects with subclinical hypothyroidism and 15 subjects whose thyroid function was completely normal. The lifetime frequency of depression was significantly higher in the subjects who met the criteria for subclinical hypothyroidism (56%) than in those who did not (20%), suggesting that subclinical hypothyroidism may lower the threshold for the occurrence of depression. PMID- 8434672 TI - Psychosocial functioning in children after the death of a parent. AB - Eight weeks after the death of a parent, children from stable families (N = 38) were compared to depressed inpatients (N = 38) and normal children (N = 19). School behavior, interest in school, peer involvement, peer enjoyment, and self esteem were similar for bereaved and normal children. Bereaved children functioned significantly better than depressed inpatients. As a group, the bereaved children from stable families did not experience significant, acute psychosocial dysfunction. PMID- 8434673 TI - Inverse evolution of emotional blunting and irritability after delivery. PMID- 8434674 TI - Toxic interaction of S-adenosylmethionine and clomipramine. PMID- 8434675 TI - Trazodone treatment of obsessive-compulsive disorder and trichotillomania. PMID- 8434676 TI - Trichotillomania, clomipramine, topical steroids. PMID- 8434677 TI - Major depressive episode secondary to antiglaucoma drugs. PMID- 8434678 TI - Prolonged ECT seizure duration in a patient taking trazodone. PMID- 8434679 TI - Split between psychodynamic and biological psychiatry. PMID- 8434680 TI - Obsessive-compulsive disorder, fluoxetine, and buspirone. PMID- 8434681 TI - Season of birth and bipolar disorder. PMID- 8434682 TI - High cholesterol levels in patients with panic disorder. PMID- 8434683 TI - Antisemitism and the collective unconscious. PMID- 8434684 TI - Verapamil in mania. PMID- 8434685 TI - Anticoagulant therapy and Alzheimer's disease. PMID- 8434686 TI - Abnormal illness behavior. PMID- 8434687 TI - Media- or fluoxetine-induced akathisia? PMID- 8434688 TI - Media- or fluoxetine-induced akathisia? PMID- 8434689 TI - The paradox of confidential communications. PMID- 8434690 TI - Psychiatric health care costs of multiple personality disorder. AB - The lifetime psychiatric health care costs of 15 women with multiple personality disorder (MPD) who were admitted to the senior author's inpatient service over a four-year period were tabulated. A calculation of the projected costs of treatment based on costs incurred since diagnosis was made, and this was compared to prediagnosis baseline costs projected forwards for ten years. The result of the calculation was a saving of $84,899.44 per patient over ten years due to the diagnosis and psychotherapeutic treatment of MPD. If the length of time in the health care system prior to diagnosis was reduced from the average of 98.77 months experienced by these 15 women to 12 months, the savings would be over $250,000.00 per case. Because the potential savings from the diagnosis and treatment of MPD appear to be so large, replication of the study with a longer followup is required. PMID- 8434691 TI - Living with mania: a study of outpatient group psychotherapy for bipolar patients. AB - This article describes an outpatient group psychotherapy with fourteen bipolar patients. Contrary to previous pessimistic reports in the literature, the author demonstrates that group therapy with these patients is both feasible and beneficial, and that it contributes to an ameloriation of the natural course of this illness. Group psychotherapy, with its enhancement of medication compliance, effective challenge of denial mechanisms, and facilitation of increased awareness of internal and external stressors, can thus be an effective tool in the therapeutic armamentarium against the ravages of bipolar illness. Significant themes arising in the group, common defensive operations, and therapeutic techniques are discussed. In addition, phases of recovery and group development are reviewed in the context of relevant interventions. Treating bipolars in group therapy is a fascinating and rewarding experience, full of potential gains in understanding and influencing the course of this complicated illness. PMID- 8434692 TI - Suicidal behavior in the nursing home and a postsuicide intervention. AB - The suicidal elderly patient in the nursing home has been the focus of inadequate attention. Given the longer life expectancy, we can project that the nursing home as a context of end-life care will be utilized by increasing numbers of elderly. This article presents a case of a suicide in a nursing home and a review of the relevant current literature. A mental health consultation to the administration and staff of the nursing home following the suicide is presented as an effective way to promote healing and limit adverse sequelae. In addition, a view of the concept of institutional care to the elderly is discussed. Relocation to a nursing home as a catalyst for suicidal behavior and the notion of "goodness of fit" as it applies to resident adaptation to the nursing home is posited. A continuum of suicidality is proposed. Suicidal ideation and Intentional Life Threatening Behaviors (ILTBs) are described as adapting to the context of the nursing home, and examples are offered. The article concludes with a model of suicide probability in the nursing home resident. PMID- 8434693 TI - Problems in the treatment of religious patients. PMID- 8434694 TI - Basic principles of psychotherapy. II. The patient model, interventions, and countertransference. AB - This paper (Part II) discusses the details of techniques used in achieving the goals of creating an individualized patient model, making effective interventions and monitoring countertransference. Models of patients' functioning can be created by using selection strategies regarding patients' characteristics and drawing on general models to explain these phenomena. Interventions are based on this model and should increase patients' understanding but are selected on the basis of goals and the individual's current state. Countertransference is a universal phenomena that can be managed in a variety of professional ways. PMID- 8434695 TI - The psychiatrist as a psychotherapist: the problem of identity. AB - Becoming a psychotherapist is a complicated process for individuals from any discipline but for physicians the process is even more difficult. We consider the identity issue to be central to the integration of psychotherapy into the training of psychiatrists. Residents can be taught that seemingly contradictory aspects of identity can coexist successfully. It is important to address this issue early in the training of residents and to provide a setting in which a positive professional identity can develop. Failure to do so can lead to frustration, anger, demoralization, and devaluation, inhibiting optimal development of skills. PMID- 8434696 TI - House of Games: a cinematic study of countertransference. AB - In this paper we have described how examining the film House of Games can lead to an enriched understanding of the concept of countertransference for both neophyte and experienced psychotherapists. This absorbing film portrays countertransference phenomena from a number of crucial perspectives: predispositions to countertransference, direct and indirect indicators, countertransference in the "totalistic" sense as well as countertransference in the "classical" sense, parallel-process dynamics between therapy and supervision and the value of social and professional support in managing this inevitable burden. Cinema is another method, along with more traditional supervisory and didactic approaches, of assisting therapists to increase their cognitive and affective mastery of countertransference phenomena by encouraging them to analyze their emotional reactions to patients. This is no small task. In summary, we believe that the recognition, analysis and management of countertransference reactions is a necessary and life long professional task for any serious psychotherapist. PMID- 8434697 TI - Basic principles of psychotherapy: introduction. PMID- 8434698 TI - Development of the psychotherapy supervisor: concepts, assumptions, and hypotheses of the supervisor complexity model. AB - The growth of the psychotherapy supervisor has been a much neglected topic in the clinical supervision literature. In an effort to better address this area, a four stage model of development through which psychotherapy supervisors generally are thought to pass has been proposed. To further flesh out this model and render its substance more explicit, this paper complements the earlier explication by (a) providing basic foundation material that supports and underlies it and (b) providing additional material that extends it. The concepts, assumptions, and hypotheses of the Supervisor Complexity Model (SCM) have been identified and delineated. Some attention has also been given to how research on the SCM might best proceed. Specifying the model in this way seems important if it is to be subject to further professional scrutiny (so that refinements/revisions in it can be made), if it is to be rendered most researchable as a heuristic paradigm, if it is to be more solidly grounded within a developmental framework, and if it is to ultimately inform supervision practice. PMID- 8434699 TI - The treatment of paranoid phenomena: the development of the self. AB - The two main problems of patients suffering from paranoid phenomena are discussed from a treatment perspective. These two problems arising from "having trusted too much" and having lost "ownership of the self" result in the classic projections and loss of initiative commonly seen in paranoid psychopathology. Clinicians must first ward off the patients' projections and help patients work toward a position of "healthy skepticism." This article shows: (1) the specific role of narcissism, its structures and processes, as they contribute to the internal changes needed to achieve this goal; (2) how clinicians can rekindle important sources of initiative and aspiration within the patient. Selfobject relationships, the agency of the ego ideal and the role of the affects of hope and affection, along with such specific interventions as "performative statements," have been offered as helpful tools for clinicians who work with paranoid patients. PMID- 8434700 TI - Basic principles of psychotherapy. I. Introduction, basic goals, and the therapeutic relationship. AB - This paper (Part I) outlines some fundamental principles of psychotherapy. The concept of "supportive" psychotherapy and the problems associated with those techniques are discussed, along with the advantage of learning basic principles of psychotherapy. The basic principles of psychotherapy are introduced in terms of basic goals. The techniques used in achieving the goal of an effective therapeutic relationship are discussed in detail. Other goals of creating an individualized patient model, making interventions, and monitoring countertransference are introduced but detailed discussion is left for Part II. PMID- 8434701 TI - Psychotherapy of the victims of massive violence: countertransference and ethical issues. AB - Psychotherapy with severely traumatized patients is a long, draining process that often produces strong countertransference reactions. It is difficult to therapeutically and ethically handle these personal responses. We feel that at different stages in therapy different ethical principles should guide the therapy. At the early stages, fidelity and nonmaleficence should be the guiding principles. As trust and confidence develop, therapists may have more personal freedom to act; beneficence, i.e., providing specific confident care then becomes the primary ethical principle. In later stages of therapy, promoting the principles of autonomy and justice come into play. As therapy further progresses, therapists' own needs, the principle of self-interest, may be utilized in the therapeutic relationship. Throughout therapeutic contacts with traumatized patients, therapists need to monitor their own needs, and find appropriate ways outside of therapy to cope with these often intense feelings. Continuing to feel therapeutically competent and ethically grounded, yet maintaining the personal strength and balance to treat traumatized patients, pose major challenges for therapists. PMID- 8434702 TI - Overexpression of the p53 tumor suppressor gene product in primary lung adenocarcinomas is associated with cigarette smoking. AB - Mutations in the p53 tumor suppressor gene are frequently observed in primary lung adenocarcinomas, suggesting that these mutations are critical events in the malignant transformation of airway cells. These mutations are often associated with stabilization of the p53 gene product, resulting in the accumulation of p53 protein. In this study, 70 formalin-fixed, paraffin-embedded primary lung adenocarcinomas resected for potential cure were examined for p53 overexpression. These 70 lung adenocarcinomas were obtained from a series of patients with well documented clinical histories, and all 70 carcinomas had been previously evaluated for point mutations in codon 12 of the K-ras oncogene. Overexpression of the p53 protein was detected using an antigen retrieval system (Target Unmasking Fluid) and the anti-p53 antibody CM-1. CM-1 is a polyclonal antibody directed against the wild-type p53 protein. Overexpression of the p53 protein was found in 23 (33%) of the 70 lung adenocarcinomas. In all 23 cases, overexpression was confined to neoplastic cells. Overexpression of the p53 protein correlated with cigarette smoking: 10 (56%) of the 18 adenocarcinomas from patients who were current smokers overexpressed p53 compared with 13 (33%) of the 40 adenocarcinomas from patients who had quit smoking and 0 (0%) of the 12 adenocarcinomas from patients who had never smoked (p = 0.002, trend test). Overexpression of the p53 protein was also related to the degree of histologic differentiation: 48% of the p53 negative carcinomas were well differentiated, whereas only 13% (p = 0.003) of the carcinomas in which p53 was overexpressed were well differentiated. Overexpression of the p53 protein did not correlate with point mutations in codon 12 of the K-ras oncogene, nor did it correlate with tumor stage or patient survival. These findings indicate that p53 protein is frequently overexpressed in primary lung adenocarcinomas. Furthermore, the association of tobacco smoking with this overexpression suggests that the p53 gene is a target of specific mutagens in tobacco smoke. PMID- 8434703 TI - Spindle cell variants of embryonal rhabdomyosarcoma in the paratesticular region. A report of the Intergroup Rhabdomyosarcoma Study. AB - We reviewed 173 cases of paratesticular rhabdomyosarcoma (RMS) of Intergroup Rhabdomyosarcoma Studies (IRS)-I, -II, and -III for evaluation of possible histological factors that might account for the good prognosis of these patients. Almost all cases (161 of 173 cases, 93.1%) occurring in this site were of embryonal histology. A spindle-cell subtype of embryonal RMS was identified that presented a storiform growth pattern with abundant collagen between the tumor cells in most cases. Other tumors of this subtype showed an arrangement of tumor cells in bundles with a low to moderate amount of collagen, resembling a leiomyosarcoma. The other embryonal RMS in this site had the classical embryonal cytology. The spindle-cell subtype was highly differentiated by immunohistochemistry and electron microscopy. Lymph node metastasis was found in seven of 43 patients (16.3%) with a RMS of spindle-cell subtype, compared with 40 of 112 patients (35.7%) with RMS of non-spindle-cell type. Clinical data from patients with spindle-cell subtypes of the paratesticular lesions revealed that they almost always had an association with clinical groups of limited disease (32 patients, 74.4%, with Group I; 10 patients, 23.3%, with Group II disease) and a significantly better prognosis (95.5% survival at 5 years) when compared with patients with the classic embryonal variant of RMS (80% survival at 5 years, p < 0.035). The incidence and anatomic distribution of this spindle cell subtype of embryonal RMS was estimated on 800 randomly selected patients from IRS-II. It was found in the head and neck, extremities, orbit, and some other sites, but 30.6% were located in the paratesticular area. Patients with spindle cell RMS of nonparatesticular sites usually had more extensive disease compared with patients having paratesticular lesions; two thirds of the cases had gross residual tumor after surgery or metastatic tumor at diagnosis. We conclude that spindle-cell RMS is a subtype of embryonal RMS with a very favorable prognosis. The site factor of the paratesticular localization may allow earlier diagnosis of the spindle-cell lesions compared with other sites. Other unknown factors may also play a role. PMID- 8434704 TI - Characterization of nuclear DNA content, proliferation index, and nuclear size in a series of 181 meningiomas, including benign primary, recurrent, and malignant tumors. AB - The characterization of nuclear area, the proliferation index, and nuclear DNA content was carried out by means of digital cell image analysis, which makes it possible to compute morphometric and densitometric features on Feulgen-stained nuclei from archival, that is, formalin-fixed, paraffin-embedded materials. The 181 meningiomas studied included 173 classic (41 meningotheliomatous, 27 fibroblastic, 82 transitional, nine psammomatous, eight angiomatous and six hemangioblastic tumors) and eight malignant meningiomas (three hemangiopericytomas and five tumors that we labeled HFM, that is, tumors exhibiting evidence of histological features of malignancy). The results reveal a strong relationship between incomplete surgical resection and recurrence on the one hand and between the probability of recurrence and histopathological type on the other. Whereas neither nuclear area nor nuclear DNA content assessments were helpful in distinguishing the six classic and the two malignant meningioma subgroups, a statistically significant increase in proliferative activity was observed in the malignant meningiomas as compared with classic ones, excepting hemangioblastomas that proliferate at the same rate as the malignant meningiomas. Furthermore, the multiple meningiomas definitely proliferated more actively than the single ones, but a similar proliferative activity was observed in the nonrecurrent and recurrent meningiomas. Proliferation analyses might be therefore helpful for determining aggressive meningiomas and for planning adjuvant therapy in these cases. PMID- 8434705 TI - Low-grade adenosquamous carcinoma of the breast. A clinocopathologic study of 32 cases with ultrastructural analysis. AB - Low-grade adenosquamous carcinoma of the breast is an uncommon neoplasm of uncertain pathogenesis, clinical behavior, and malignant potential. This report describes the clinical and pathologic features of 32 cases of low-grade adenosquamous carcinoma. All patients presented with palpable tumors ranging from 0.6 to 8.6 cm (mean, 2.8 cm). Origin from an intraductal papillary tumor was found in 12 cases, including three with adenomyoepitheliomatous features. Electron microscopy disclosed glandular and squamous differentiation; the squamous cells often lined ducts that were structurally analogous to the acrosyringium of the eccrine sweat gland. Treatment consisted of mastectomy (13 patients) or excisional biopsy (19 patients). A single lymph node in one patient with a 3.5-cm primary carcinoma harbored metastatic adenocarcinoma. Axillary dissection revealed no metastases in 11 other patients. Another patient with an 8.0-cm breast tumor had metastatic adenosquamous carcinoma in the lung at initial diagnosis. After follow-up of 12 to 124 months, 20 of 25 patients had no recurrence. Five women treated by excisional biopsy had local recurrences in the breast. In one patient, the local recurrence was ultimately fatal due to invasion of the hemithorax. Estrogen and progesterone receptor studies were negative in 13 of 15 cases studied by biochemical analysis. The two tumors that were hormone receptor positive were histologically associated with a papilloma and an adenomyoepithelioma, respectively. In the latter case, immunohistochemical studies showed the carcinoma to be hormone-receptor negative. Hormone receptor activity was limited to the adenomyoepitheliomatous component. This study confirms the largely indolent, but locally aggressive, clinical course of low grade adenosquamous carcinoma of the breast. Although complete limited excision of small lesions may be curative, tumors greater than 3.0 cm may require more aggressive therapy. PMID- 8434706 TI - Lichen planus-like keratosis. A clinical and histological reexamination. AB - Lichen planus-like keratosis (LPLK) is a common skin lesion that has some morphologic features of lichen planus (LP) and lichenoid actinic keratosis (LAK). Although most authors consider LPLK to be a distinct lesion, surgical pathologists are often unfamiliar with it. We examined in detail the clinical and histologic features of LPLK in 100 consecutive cases. In our series, LPLK lesions occurred mostly in late-middle-aged individuals, on the trunk (64%) and extremities (31%) and predominantly in women (73%). Among the 14 histologic parameters that were studied, most LPLK had hyperkeratosis (81%) with hypergranulosis (77%), focal acanthosis (75%), and focal parakeratosis (59%). Solar elastosis was observed in 48% of the cases. Only a few cases had eosinophils (15%) or plasma cells (7%) in the inflammatory infiltrate. The adjacent skin was available for study in 71% of the specimens, and only 26.8% of the cases had an adjacent lesion, most frequently seborrheic keratosis (8.4%), solar lentigo (7%), and actinic keratosis (5.6%). According to our results, the most consistent features observed in LPLK are a lichenoid lymphocytic infiltrate with hyperkeratosis, hypergranulosis, focal acanthosis, and focal parakeratosis, without prominent atypia of keratinocytes. PMID- 8434707 TI - Inflammatory pseudotumor of the urinary bladder. A clinicopathological, immunohistochemical, ultrastructural, and flow cytometric study of 13 cases. AB - We report 13 cases of inflammatory pseudotumor of the urinary bladder in patients having no history of recent local trauma. The average age of the patients (eight females, five males) was 35.4 years (range, 19 to 60 years). Gross hematuria (nine of 13 cases) and recurrent cystitis (three of 13 cases) were the most common presentations. Cystoscopy and gross examination revealed either a polypoid intraluminal mass or a submucosal mural mass, ranging in size from 2 to 7 cm. The lesions were commonly gelatinous. Histological examination showed that the lesions consisted of spindle cells with tapering eosinophilic cytoplasm, typically widely separated in a vascular myxoid matrix with acute and chronic inflammatory cells. In four cases the lesions had more compact cellularity with areas of fibrosis and less myxoid change. The muscularis propria was involved in 10 cases, the perivesical fat in two cases. The spindle cells were immunoreactive for vimentin (10 of 10) and muscle-specific actin (10 of 10). A few cases exhibited immunoreactivity for smooth-muscle-specific actin (three of eight), cytokeratin (two of 10), desmin (two of nine), and epithelial membrane antigen (two of eight). Ultrastructural examination of four cases revealed myofibroblasts, fibroblasts, or a mixture of the two cell types. DNA content analysis by flow cytometry yielded diploid histograms (six of six). Clinical follow-up in all cases demonstrated no evidence of recurrence (mean follow-up, 25.8 months). The findings indicate that this lesion is a benign, likely inflammatory or reparative, mesenchymal lesion that can be recognized by its distinctive pathological features. PMID- 8434708 TI - Stage I renal cell carcinoma. A clinicopathologic study of 82 cases. AB - Stage has been established as the most important predictor of prognosis in renal cell carcinoma. The predictive value of other morphologic features is less well established. Therefore, in this study we assessed morphologic parameters in 82 Robson stage I renal cell carcinomas. Insufficient numbers of T1 lesions were present in this series to permit a confident comparison of Robson staging with the Union Internationale Contre le Cancer-American Joint Committee on Cancer TNM (tumor, node, metastasis) staging. Morphologic parameters--including size, character of cytoplasm, nuclear grade, and pelvic invasion--were studied. Both univariate survival analysis and multivariate or tree-structured survival analysis (TSSA) were employed, with disease-free survival and actuarial survival as end points. Nuclear grade was the most important predictor of prognosis in stage I neoplasms by TSSA. Nuclear grade greater than 2 correlated with significantly shorter survival (p = 0.018). Stage I tumors measuring less than 5.0 cm by survival analysis (or 6.0 cm by TSSA) were associated with improved disease-free survival (p = 0.040), although TSSA indicated that the effect was pronounced only in low-grade neoplasms. The character of cell cytoplasm was not independent of nuclear grade (Kruskal-Wallis test, p = 0.028). The contingency table indicated disproportionate numbers of grade 4 mixed cell tumors, grade 3 granular cell tumors, and low-grade clear cell tumors. By TSSA, younger patients with low-grade but larger tumors had a poor clinical outcome. Elderly patients with high-grade tumors had the worst overall survival. None of the other clinical parameters or architectural pattern correlated with survival or disease-free survival. When nuclear grade was combined with tumor size and age at diagnosis in a decision tree, patients with stage I neoplasms were separated into favorable, intermediate, and poor prognosis groups. PMID- 8434709 TI - Poorly differentiated thyroid carcinomas with primordial cell component. A group of aggressive lesions sharing insular, trabecular, and solid patterns. AB - Poorly differentiated carcinomas of the thyroid share insular, trabecular, and solid histological patterns that are different from those of papillary, follicular, medullary, and anaplastic varieties. We have collected 63 cases of poorly differentiated thyroid carcinomas. Thirty-one tumors (Group A) corresponded to the so-called insular carcinomas, and 32 tumors (Group B) had predominant trabecular and solid or focally follicular patterns in the presence of a minor insular component. The cells characterizing these lesions were relatively small and globoid, with uniform nuclei and intracytoplasmic deposits of thyroglobulin. They were in every respect similar to primordial cells present in the early stages of fetal thyroid development. None of the tumors proved fatal within 6 months, and most responded to radioiodine therapy. Although no differences in survival between the two groups were found, a significantly (p < 0.01) higher percentage of recurrences or distant metastases was observed with Group A tumors. The term primordial cell carcinoma appears appropriate for this type of tumor, which displays characteristic histocytological features and production of thyroglobulin. Clinically, these tumors are aggressive but generally show a slow course and good response to radioiodine therapy. PMID- 8434710 TI - Solitary infantile myofibromatosis of bone. An immunohistochemical and ultrastructural study. AB - A rare case of solitary infantile myofibromatosis of bone in an 11-month-old boy is reported. Radiographically the lesion of parietal bone was round, well circumscribed, and osteolytic with a sclerotic rim. Histologically the tumor was made up of nodules that were hyalinized or cellular and containing plump, spindle shaped cells that were intermediate in appearance between fibroblasts and smooth muscle cells, arranged in short bundles or whorls. Another typical feature was the presence of distended, cleft-shaped vascular spaces around the nodules. The microscopic features of this tumor were consistent with those of infantile myofibromatosis of other sites, such as the skin and deep soft tissue. The tumor cells showed immunoreactivities for vimentin and alpha-smooth muscle actin. Microfilaments with dense bodies were observed in the fibroblast-like tumor cells. In addition, many tumor cells stained for collagen type IV and were covered by incomplete external laminae, indicating infantile myofibromatosis has more advanced smooth-muscle differentiation than conventional fibromatosis. PMID- 8434711 TI - Pseudotuberculous pyelonephritis associated with nephrolithiasis. PMID- 8434712 TI - Kaposi-like infantile hemangioendothelioma. PMID- 8434713 TI - Actinomycosis of the infratemporal fossa. PMID- 8434714 TI - Preservation of vestibular nerves in surgery of the cerebellopontine angle: effect on hearing and balance function. AB - INTRODUCTION: Small tumors of the cerebellopontine angle (CPA) can frequently be removed with preservation of the auditory and the vestibular portion of the eighth cranial nerve. This study was undertaken to estimate the effect of vestibular nerve preservation on both balance and hearing following surgery. MATERIALS AND METHODS: A retrospective study of all cases of CPA lesions between 1987 and 1991 was undertaken. This identified 11 patients in whom either the superior and/or inferior vestibular nerves were preserved. This included eight acoustic neuromas and three meningiomas. The retrosigmoid approach and total tumor extirpation was undertaken in all cases. Patients undertook a vestibular questionnaire, audiometric testing, and evaluation of vestibulo-ocular responses preoperatively and postoperatively. Additionally, static and dynamic platform posturography was performed postoperatively in 9 of 11 patients. RESULTS: Follow up ranged from 6 to 44 months. Of the eight patients with acoustic neuroma, four had a preoperative balance disorder that resolved postoperatively. One patient died of unrelated causes. Of the remaining seven patients with caloric testings, one maintained normal caloric responses. A persistent postoperative phase shift was noted in 4 of the 7 cases with rotatory testing. Three patients were treated for a meningioma. All had a preoperative balance disorder that resolved postoperatively. Two patients showed vestibular response indicative of residual but compromised function on the involved side. The third patient showed absent responses indicating an anatomically intact nerve that does not necessarily predict functional activity. Preservation of the vestibular nerve was associated with preservation of preoperative hearing in five of the patients. This included four of the eight acoustic patients and one of the three meningioma patients. CONCLUSIONS: Preservation of the vestibular nerve did not result in a chronic balance disorder in this patient population. This study does not allow the authors to conclude if vestibular nerve preservation improves overall hearing after CPA surgery; however, these data suggest that preservation of the inferior vestibular nerve may result in less damage to the cochlear nerve in some patients. Accordingly, preservation of the vestibular nerve in CPA meningioma surgery can be recommended. PMID- 8434715 TI - Is emergency laryngectomy a waste of time? AB - INTRODUCTION: Patients who present with airway obstruction due to carcinoma of the larynx may be managed by tracheotomy followed by definitive tumor surgery at a later date. An alternative is emergency laryngectomy, defined as total laryngectomy performed within 24 hours, for a previously untreated and undiagnosed malignancy. In this study, we compare and contrast the outcome of 13 patients managed by tracheotomy and delayed laryngectomy to another group of patients, previously reported, managed by emergency laryngectomy. MATERIALS AND METHODS: Stridor due to malignant laryngeal neoplasm was treated by tracheotomy and delayed definitive laryngectomy in 13 patients. In every case, the tracheostomy site was removed with a surgical specimen. A comparison of the survival data was performed with earlier reported series of 13 emergency laryngectomies using the Wilcoxon log rank method. RESULTS: All patients were followed for a minimum of 24 months. Seven patients underwent postoperative radiotherapy. Two of these patients (15%) developed peristomal recurrence at 6 and 22 months respectively. Both died of disease. Six patients from each group survived disease free for a minimum of 24 months. No significant correlation was found between the time delay of definitive surgery and survival (P > .5). DISCUSSION: This series suggests that emergency laryngectomy offers patients no survival advantage. Emergency laryngectomy does, however, have several disadvantages. These include the necessity to rely on frozen section analysis, the difficulty in obtaining expert anesthetic support, and the inability to provide thorough and complete nutritional and metabolic work up before major surgery. Finally, the psychologic aspects of radical surgery for patient and family cannot be adequately addressed. We conclude that stomal recurrence is as much a function of extensive disease at presentation as of preliminary tracheotomy. Emergency laryngectomy is not a superior treatment modality and offers no particular survival advantage. PMID- 8434716 TI - Summating-potential/action-potential ratio in normal ears: effects of dehydration. AB - INTRODUCTION: Studies using electrocochleography (ECoG) in patients with Meniere's disease and in patients with perilymph fistula have demonstrated abnormally large summating-potential (SP) components compared with the amplitude of the action-potential (AP). The possible influence of normal physiological variation, methodological differences, and test-retest variations are often difficult to interpret. The purpose of this study is to specify what constitutes a clinically important change in the SP/AP ratio in normal hearing subjects under the condition of dehydration induced by urea. MATERIALS AND METHODS: Baseline ECoG was performed on 20 normal hearing volunteer subjects after an 8 hour fast. Urea, 20 g, was administered orally, following which recordings were made at 60 and 90 minutes. The majority of subjects were found to have maximal SP/AP changes at 60 minutes post dehydration; therefore, only these results were included in the final analysis. Subsets of data were statistically evaluated. RESULTS: In all ears but one, the preingestion SP/AP ratio was less than or equal to 0.37. Male and female data were shown to comprise separate populations both before and following dehydration. The 95% upper limit for baseline SP/AP ratio was 0.39 for males and was 0.25 for females. The gender-related difference remained after dehydration. The mean male SP/AP ratio showed a statistically significant but slight decrease whereas the female SP/AP ratio was unaltered. CONCLUSION: These data demonstrate a statistically significant gender-related difference in SP/AP ratio in normals. The upper limit of normal is 0.39 for males and 0.25 for females. A basis for the gender difference is puzzling and requires further investigation. Dehydration produces a statistically significant reduction in SP/AP ratio in men. This change was not observed in women. PMID- 8434717 TI - Advanced carcinomas of the oropharynx treated with radiotherapy--a comparison of three different fractionation schemes. AB - INTRODUCTION: This report reflects a retrospective comparison among historical series of patients with similar site and stage of disease treated by three fractionation schemes. MATERIALS AND METHODS: A hyperfractionation (HF) scheme delivered 1 Gy three times a day, 5 days a week, to a total dose of 60 to 63 Gy over 26 to 29 days. A group of 48 patients received HF. Accelerated fractionation (AF) consists of 2 Gy three times a day, 5 days a week, to a total of 48 to 52 Gy delivered over 11 to 12 days. A group of 46 patients underwent this therapy. A third group of 48 patients were treated with conventional fractionation (CF). These patients received 2 Gy each day, 5 days a week, to a total dose of 60 to 66 Gy. RESULTS: Ned survival at 5 years was 23.8%, 32.8%, and 29.3% for CF, AF, and HF, respectively. The most important cause of failure was inability to control disease at the primary site; however, isolated distant metastasis were observed in 15.4% of all failures. Treatment delays were more common in the HF and CF groups. The highest incidence of late complications occurred in the AF group. CONCLUSIONS: Advanced lesions of the oropharynx have an ominous prognosis. New fractionation regiments represent a warranted approach as an alternative to or an integration into combined chemotherapy and radiotherapy. PMID- 8434718 TI - Fractures of the temporal bone--chain incongruencies. AB - PURPOSE: The sequela of a temporal bone fracture include hearing loss, vestibular dysfunction, and facial nerve injury. A large series of patients with temporal bone fractures are reviewed to correlate mechanism of injury, fracture location, and outcome. PATIENTS AND METHODS: A retrospective analysis of patients evaluated between 1978 and 1987 for temporal bone fractures at two Swedish clinics was undertaken. Assessment of auditory, vestibular, and facial nerve function is reported. Follow up varied from 3 months to 12 years. RESULTS: A total of 72 temporal bone fractures were encountered. Eleven patients had chain incongruencies, nine of whom were operated on with resultant good hearing. Transverse fractures were associated with severe sensorineural hearing loss while longitudinal fractures frequently were accompanied by ossicular disruption and persistent conductive hearing loss. Patients with vertigo or dizziness frequently had a good prognosis. Facial nerve injury occurred in 14 patients, eight of whom recovered. CONCLUSIONS: Hearing loss following temporal bone fracture reflects the site and mechanism of injury. Transient conductive hearing loss may be due to blood in the middle ear, perforation of the tympanic membrane, or injury to the ossicular chain. Conductive loss persisting 6 to 7 weeks after trauma and exceeding 30 dB is an indication for surgical exploration. PMID- 8434719 TI - Misdirected regeneration of injured recurrent laryngeal nerve in the cat. AB - INTRODUCTION: Misdirected regeneration (MR) frequently occurs following injury to the recurrent laryngeal nerve (RLN) resulting in neurotmesis or axonotmesis. Physiological and anatomic parameters involved in the functional recovery of the larynx following freezing injury or neurorrhaphy of the RLN were studied. A multi facilitated approach is undertaken to clarify the functional abnormalities caused by the MR after recurrent laryngeal nerve injury. MATERIALS AND METHODS: Three groups of adult cats were studied. These included controls, cats with recurrent laryngeal neurorrhaphy, and cats with recurrent laryngeal nerve freeze injuries. From 2 weeks to 9 months after the nerve injury, the animals were studied endoscopically and with electromyography (EMG). Using the same animal, the number and location of motoneurons supplying the ipsilateral posterior cricoarytenoid (PCA) muscle were examined with horseradish peroxidase (HRP). Animals were subsequently sacrificed to study the pattern of reinnervation. RESULTS: Following neurorrhaphy all cats had vocal cord paralysis. After neurorrhaphy, effective motion function did not return in the affected vocal cord and it remained fixed in the paramedian position. Although EMG of the laryngeal muscles of the affected side showed interference voltage, the pattern of activities was markedly different from that of the unaffected side, and reciprocity among the laryngeal muscles was not restored. The number of PCA motoneurons recovered to the normal range, but a considerable number of neuronal bodies were dispersed outside the normal PCA area. This indicates misdirected reinnervation to the PCA muscle by motoneurons that originally served other laryngeal muscles. In the freezing injury, effective vocal cord movement finally recovered after 6 months. At this time, EMG showed a normal pattern, although a relatively small amount of misdirected neurons was observed. DISCUSSION: Functional recovery of vocal cord motion does not occur following neurorrhaphy. Prominently disorganized arrangement of laryngeal motor neurons was observed in the horseradish peroxidase study. This suggests that inappropriate reinnervation develops in spite of reapproximation and suturing. Altered central organization of the motor nucleus is a significant pathogenic factor in the loss of laryngeal muscular coordination following recurrent laryngeal nerve lesions. The degree of recovery is related to the mechanism of injury. PMID- 8434720 TI - Fate of patients with bilateral cholesteatoma. AB - INTRODUCTION: This study was designed to assess the clinical and surgical findings and long-term results of therapy in patients treated for bilateral chronic cholesteatomatous otitis media. PATIENTS AND METHODS: A series of 54 patients who underwent mastoid surgery for bilateral acquired cholesteatoma were followed regularly for a mean of 7.9 years (range 2 to 21 years). Results of treatment were compared with the results obtained in 349 patients treated for unilateral acquired cholesteatoma with a mean follow-up of 6.7 years. Hearing level was defined as the mean air conduction threshold at frequencies of 0.5, 1, and 2 kHz. Audiograms obtained the day before operation and at last follow-up examination were used for comparison. Results were analyzed using the t test and chi 2 test. RESULTS: Patients with bilateral cholesteatoma were more likely to be men (60% v 61%) and young (28 years v 38 years). A majority of patients underwent canal wall down mastoidectomy. Seventy-three percent of patients had ossicular erosion. During follow-up, residual recurrent cholesteatoma was found in 8 ears (7.4%). This compared with a recurrence rate of 8.3% in patients with unilateral cholesteatoma. The mean postoperative air conduction threshold (46.1 dB) was similar to patients with unilateral cholesteatoma (46.6 dB). At last follow-up, 43% of patients with bilateral cholesteatoma had a hearing level of 30 dB or better in their best ear. No patient had bilateral anacusis. DISCUSSION: Cholesteatoma is a burdensome disease. Our 54 patients with bilateral cholesteatoma underwent a total of 125 surgical procedures. Acquired cholesteatoma has a great tendency to recur. Fortunately, this study shows that recurrence is not higher in a group of patients with bilateral cholesteatoma when compared with the unilateral group. Unfortunately, the fate of hearing in patients with bilateral cholesteatoma is not so favorable. Only 19% had hearing levels of 30 dB or better in both ears. Hearing levels of less than 40 dB in one ear was present in 34% of patients. Fortunately, there was no case with severe sensorineural hearing loss as a complication of surgery in the present series. This reflects great efforts directed at reduction of infection preoperatively, avoidance of ossicular manipulation, and preservation of cholesteatoma matrix over fistula when encountered. PMID- 8434721 TI - Kaposi's sarcoma of the head and neck in acquired immunodeficiency syndrome. AB - Kaposi's sarcoma has emerged from obscurity to become a common treatment problem. Otolaryngologists can play a key role in diagnosis and treatment of the victims of AIDS given the frequency of involvement of the head and neck. Kaposi's sarcoma involvement of the head and neck is often the presenting symptom of AIDS, making accuracy in diagnosis critical if intervention is to begin early. KS is rarely the cause of death in these patients, although it can cause significant morbidity. Treatment is currently directed toward palliation for pain, bleeding, dysphagia, airway obstruction, severe disfigurement, and prophylaxis for rapidly progressive tumor. The choice of treatment is dependent on the symptoms, location, and extent of the lesion. Radiation, chemotherapy, and alpha interferon form the core of treatment, with the former two more commonly used. The general medical condition of the patient must be considered, particularly when systemic treatment is contemplated. Future directions of therapy may be directed toward optimizing combination therapy and modification of the underlying immunodeficiency to allow the body's own compromised immunity to cause regression of the tumor. PMID- 8434722 TI - Corkscrew esophagus. PMID- 8434723 TI - Transcutaneous frontal sinus trephination with endoscopic visualization of the nasofrontal communication. PMID- 8434724 TI - Cochlear histopathology in Paget's disease. PMID- 8434725 TI - The EUROSCAN study: a progress report. PMID- 8434726 TI - Chronic fatigue relieved by a nasal dilator. PMID- 8434727 TI - Solitary cutaneous malignant schwannoma. Immunohistochemical and ultrastructural studies. AB - We describe two cases of malignant schwannoma in the skin that did not originate from a nerve trunk and was not associated with neurofibromatosis. Light microscopy showed that both tumors were composed predominantly of atypical spindle-shaped cells. Immunohistochemical analysis was performed with various monoclonal antibodies against mesenchymal determinants. In both patients, tumor cells were positive for S-100 alpha and S-100 beta, neuron-specific enolase, vimentin, neurofilament protein, and myelin basic protein, and negative for HMB 45, glial fibrillary acidic protein, epithelial membrane antigen, and desmin. Electron microscopy revealed that the tumor cells possessed indented nuclei with an electron-lucent cytoplasm. Immunoelectron microscopy showed diffuse fine granular staining for S-100 alpha, not detectable in normal Schwann cells, in the cytoplasm of the tumor cells. PMID- 8434728 TI - Expression patterns of loricrin in dermatological disorders. AB - Loricrin is a glycine-, serine-, and cysteine-rich protein expressed very late in epidermal differentiation in the granular layers of normal human epidermis. Subsequently, loricrin becomes cross-linked by the activity of transglutaminases TGK/E as a major component of the cornified cell envelope by N epsilon-(gamma glutamyl)lysine isopeptide bonds. In this study, 115 biopsy specimens from patients with various cutaneous diseases with a morphologically altered epidermal differentiation were analyzed with use of immunohistology with antibodies to loricrin and to involucrin. In addition, antibodies to filaggrin were used for ichthyotic lesions. In contrast to involucrin, loricrin expression was consistently down-regulated in agranulotic, parakeratotic keratinization as observed in psoriasis, dermatitis, pityriasis lichenoides, porokeratosis, or precancerous and malignant squamous lesions. High levels of loricrin were found in hypergranulotic and hyperorthokeratotic epidermis as observed in lichen planus, benign papillomas, and pseudocarcinomatous hyperplasia. Eleven biopsy specimens from patients with ichthyosis vulgaris showed a normal staining in the granular layers. Our results demonstrate that loricrin expression is closely linked to an orthokeratotic phenotype of human epidermal keratinization. The different expression patterns of loricrin and involucrin provide further evidence that these proteins are regulated by different mechanisms and serve different functions during terminal epidermal differentiation. PMID- 8434729 TI - The evolution of pyoderma gangrenosum. A clinicopathologic correlation. AB - Pyoderma gangrenosum is a well-known clinical cutaneous condition, that has had a variety of conflicting microscopic descriptions. In an attempt to further our understanding of this condition, we obtained nine skin biopsy specimens of evolving, fully developed, regressing, and resolved lesions from six patients with pyoderma gangrenosum. We found that histopathologically, pyoderma gangrenosum evolves from folliculitis and abscess formation; it may also show leukocytoclastic vasculitis. The lesions then evolve to suppurative granulomatous dermatitis and finally regress with prominent fibroplasia. We illustrate the clinical and microscopic features herein and compare them to previous descriptions. PMID- 8434730 TI - National Institutes of Health Consensus Development Conference Statement on Diagnosis and Treatment of Early Melanoma, January 27-29, 1992. AB - The National Institutes of Health Consensus Development Conference on Diagnosis and Treatment of Early Melanoma brought together experts in dermatology, pathology, epidemiology, public education, surveillance techniques, and potential new technologies, as well as other health care professionals and the public, to address (a) the clinical and histological characteristics of early melanoma; (b) the appropriate diagnosis, management, and follow-up of patients with early melanoma; (c) the role of dysplastic nevi and their significance; and (d) the role of education and screening in preventing melanoma morbidity and mortality. Following 2 days of presentations by experts and discussion by the audience, a consensus panel weighted the evidence and prepared a consensus statement. The panel agreed (a) that melanoma in situ is a distinct entity that can be treated effectively by surgery with 0.5-cm margins and that thin, invasive melanoma < 1 mm thick has the potential for long-term survival in < 90% of patients after surgical excision with a 1-cm margin; (b) that elective lymph node dissections and extensive staging evaluations should not be recommended in early melanoma; (c) that patients with early melanoma are at low risk for relapse but may be at high risk for development of subsequent melanomas and therefore should be followed closely; (d) that some family members of patients with melanoma are at increased risk for melanoma and therefore should be enrolled in surveillance programs; and (e) that education and screening programs have the potential to decrease morbidity and mortality from melanoma. The full text of the consensus panel's statement follows. PMID- 8434731 TI - What is early melanoma? AB - One of the goals of the National Institutes of Health Consensus Development Conference on Diagnosis and Treatment of Early Melanoma is to facilitate communication between experts in a variety of disciplines. Toward that end, this paper explores the definition of "early" melanoma from a number of perspectives, including experimental, clinical, epidemiological, and legal. PMID- 8434732 TI - A critique of an N.I.H. Consensus Development Conference about "early" melanoma. PMID- 8434733 TI - A case of nodular cutaneous amyloidosis. Amyloid production by infiltrating plasma cells. AB - We report a solitary nodular form of primary cutaneous amyloidosis due to locally infiltrating plasma cells. An 81-year-old Japanese women presented with a scarlet, dome-shaped 1.5-cm nodule with an irregular surface. Histology showed thick deposits of eosinophilic, oval, and homogeneous bodies in the dermis with mild infiltrates of mononuclear cells. The homogeneous bodies stained positively with periodic acid-Schiff, Congo red, and Yanagihara's Dylon stain, and immunohistochemically with anti-human lambda light-chain antibody. Methylgreen pyronine staining revealed that approximately half of the cellular infiltrates around the vessels were plasma cells. Electron microscopy demonstrated the homogeneous bodies to be amyloid masses, a part of which were in the cytoplasm of the plasma cells. Laboratory examination showed a slight elevation of IgG but no obvious findings suspicious for systemic amyloidosis or gammopathy. PMID- 8434734 TI - Fatal keratitis ichthyosis and deafness syndrome (KIDS). Aural, ocular, and cutaneous histopathology. AB - We report a case of KID (Keratitis, Ichthyosis, and Deafness) syndrome in which the patient died at the age of 2 months. Detailed histological study of the affected organs, particularly the inner ear and external auditory meatus, was performed. This case is the first in which previously described principles relating to the biology of the ear canal epithelium have been applied to a patient with skin disease affecting this area. PMID- 8434735 TI - Cutaneous neuroblastoma. Peripheral neuroblastoma. AB - Cutaneous neuroblastoma (CN) is a rare tumor in adults. Histologically CN can be confused with other small, round cell tumors, especially with Merkel cell tumor. This is the second case that we have encountered in a 6-year period. A 46-year old man with severe adult respiratory distress syndrome had a 2.5 x 2.0 x 2.0-cm, rapidly growing, fleshy nodule over his nose. The clinical impression was pyogenic granuloma (PG) or keratoacanthoma (KA). Histologically, the tumor showed undifferentiated cells with frequent Homer Wright rosettes and mitoses. Conventional special stains and a broad panel of immunohistochemical markers were applied that were positive only for neuron-specific enolase. Ultrastructurally the cells contained dense-core granules and immature desmosomes. The diagnosis of CN was made and an extensive radiologic and laboratory workup was initiated, but the results were negative for another primary tumor. The patient subsequently died and a thorough postmortem examination revealed multiple visceral metastatic lesions but no primary tumors in the adrenal glands, the sympathetic chain, or the central nervous system. CONCLUSIONS: (a) CN does occur in adults and can mimic other fast-growing tumors of the skin, for example, PG or KA; (b) the diagnosis of CN requires the combined use of immunohistochemistry and electron microscopy; and (c) the dermatologist should be aware of this rare, but important, tumor because its primary cutaneous manifestation may enable early recognition. PMID- 8434736 TI - Disseminated epidermolytic acanthoma. AB - A 57-year-old man developed hundreds of light brown, slightly atrophic papules, which were distributed diffusely over the back. Although clinically the lesions resembled seborrheic keratoses, histologic examination demonstrated changes of epidermolytic hyperkeratosis. The patient had neither a personal nor a family history of ichthyosiform disorders. The diagnosis of disseminated epidermolytic acanthoma was made in the context of the clinical, histologic, and historical features. Disseminated epidermolytic acanthoma is a rare condition that is readily diagnosable using clinicopathologic correlation; it is important to exclude it from other more serious conditions associated with epidermolytic hyperkeratosis. PMID- 8434737 TI - Cutaneous hamartoma of adnexa and mesenchyme. A variant of folliculosebaceous cystic hamartoma with vascular-mesenchymal overgrowth. AB - We describe a hamartoma with folliculosebaceous and mesenchymal components. Striking vascular-mesenchymal elements distinguish this entity from previously described hamartomas and other adnexal proliferations. It is also distinct from the recently described folliculosebaceous cystic hamartoma but likely represents a variant with mesenchymal overgrowth. PMID- 8434738 TI - Primary osteoma cutis. Clinical, morphological, and ultrastructural study. AB - Primary osteoma cutis arises in the deeper dermis for no apparent reason and presents as mature, lamellar, and osteonic bone; secondary cutaneous osteomas are correlated with inflammatory processes, scars, or dysembryoplasia and are always composed of osteoid. Ultrastructural findings of primary cutaneous osteomas have not been reported to date. Light and electron microscopic findings of a case of primary osteoma cutis are described: mineralized areas may be divided into macrocalcification and microcalcification. Macrocalcification consists of lamellar bone. Osteocytes populate the lamellae, whereas collagen fibril distribution is bone-like. Hydroxyapatite deposition presents as globular or needle-like electron-dense material progressively masking the connective tissue matrix. Microcalcifications, which are found in macroscopically normal dermis around the calcified plaque, consist of osteoid tissue inhabited by osteoblast like cells. Microcalcifications may be interpreted as metastatic calcifications related to the primary osteoma calcified plaque. Primary osteoma cutis may be considered as true bone amartothic formation rather than dermal mineralization. PMID- 8434739 TI - Silicone lymphadenopathy. A case report and review of the literature. AB - A case of silicone lymphadenopathy secondary to silicone mammary implantation is reported. With the recent publicity regarding possible adverse effects of silicone, pathologists need to be aware of this rare complication of silicone implantation. PMID- 8434740 TI - A critical analysis of textbooks of dermatopathology in historical perspective. Part 5. PMID- 8434741 TI - A cost-benefit analysis of intensive therapy. AB - The daily costs of 90 critically ill patients treated on an intensive therapy unit were calculated on an individual patient basis. Twenty-one patients (23%) died on the intensive therapy unit and another 13 (15%) died within one year of discharge. The results demonstrate that there is wide variation in costs among the patients and the diagnoses. The mean daily cost of nonsurvivors was almost 300 pounds greater than that of survivors (816 pounds (95% confidence interval = 649-982 pounds) versus 550 pounds (498-601 pounds). Renal failure, sepsis and pneumonia proved to be some of the most expensive conditions to treat, and postoperative respiratory failure the cheapest. The cost of the first day of management was significantly related to the APACHE II score and individual costs on the first day may be predicted from admission APACHE II score. Patients who die in the intensive therapy unit continue to incur the same level of expenditure throughout admission. The study could not provide conclusive answers concerning the trend in daily costs for survivors. PMID- 8434742 TI - The effect of fentanyl administered epidurally by patient-controlled analgesia, continuous infusion, or a combined technique of oxyhaemoglobin saturation after abdominal surgery. AB - The aims of this study were to determine the effect of three different modes of epidural administration of fentanyl on oxyhaemoglobin saturation and pain control. Forty-three patients undergoing elective abdominal surgery were randomly allocated to the following groups: (1) continuous infusion of fentanyl at a rate of 50 micrograms.h-1 with additional epidural boluses (25 micrograms) as required; (2) patient-controlled analgesia using a 25 microgram epidural bolus of fentanyl with a 15 min lock-out period; (3) a combination of patient-controlled analgesia and continuous infusion. Oxyhaemoglobin saturation was measured by continuous computerised pulse oximetry for 48 h after operation together with pain and sedation scores. In the first 24 h after surgery patients in the continuous infusion group spent a significantly greater proportion of time below oxygen saturations of 94% and 85% than those in the other two groups. On day 2 all oxygen saturation measurements were worse than during day 1, but differences between groups were not significant. Those patients receiving patient-controlled analgesia required significantly less fentanyl than patients in either of the other groups (p < 0.05). However, the mean pain and sedation scores did not differ significantly between the three treatment groups. There was no association between total fentanyl dose and oxygen saturation values. Overall, self administered fentanyl appeared to cause less oxyhaemoglobin desaturation than nurse-administered analgesia without any loss of analgesic effect. PMID- 8434743 TI - Critical incident reporting in an anaesthetic department quality assurance programme. AB - The critical incident technique was introduced as an additional form of quality assurance to an anaesthetic department of a major Hong Kong teaching hospital. In one year, 125 critical incidents were reported from over 16,000 anaesthetics. The most common incidents reported concerned the airway, breathing systems, and drug administration, with inadequate checking of equipment a frequent associated factor. Human error was a factor in 80% of incidents. Critical incidents were reported for the time during which the patient was under the anaesthetist's care. The majority occurred at induction or during anaesthesia, and were reported for all surgical subspecialties. Half of the incidents were detected by the anaesthetist and one third by monitoring equipment. Although there were improvements in anaesthetic care as a consequence of increased vigilance, critical incidents still occurred. Critical incident reporting highlighted problems not otherwise covered by case and peer reviews, and complemented our quality assurance programme. PMID- 8434744 TI - Growth of micro-organisms in solutions of intravenous anaesthetic agents. AB - This controlled bench study compared the growth of bacteria and yeast in solutions of commonly used intravenous anaesthetic agents at room and body temperatures. Drugs presented in aqueous emulsions support both bacterial and fungal growth. Five out of the six solutions supported the growth of yeast. The one exception was chlormethiazole, which is both fungicidal and bactericidal. Solutions of drugs which will support growth of micro-organisms should be used with great care and they should not be stored or infused over prolonged periods. PMID- 8434745 TI - Training nursing staff in airway management for resuscitation. A clinical comparison of the facemask and laryngeal mask. AB - The place of the laryngeal mask in emergency airway management by nonanaesthetists has yet to be established. We have compared the tidal volume achieved by nurses during hand ventilation using standard resuscitation equipment with a facemask, with or without a Guedel airway, and following placement of a laryngeal mask in the same patients. The tidal volumes measured while using the laryngeal mask were significantly greater (p < 0.01) than those measured during facemask ventilation. PMID- 8434746 TI - Effects of halothane and isoflurane on beta-endorphin release in children. AB - We compared the effects of halothane and isoflurane with 50% nitrous oxide (seven children each) on plasma beta-endorphin concentrations in a group of 14 children aged 1 to 6 years. The findings were compared for four periods of anaesthesia: basal, induction, maintenance and recovery. Beta-endorphin release was most increased with isoflurane, especially during the maintenance period. Measurements of haemodynamic parameters (heart rate and blood pressure) showed diastolic blood pressure significantly lower after isoflurane anaesthesia. The findings suggest that the use of isoflurane for paediatric inhaled isoflurane anaesthesia leads to a more marked surgical stress adaptation effect than the use of halothane. PMID- 8434747 TI - Plasma volume estimation using indocyanine green. A single intravenous injection method. AB - The validity and reliability of plasma volume estimation using indocyanine green were investigated in five in vitro experiments and in three in vivo series. The in vitro measurements reflected real volumes with an error of about 1%. Comparative measurements in the same patients using indocyanine green or Cr51 labelled red cells differed by 1.7% (r = 0.97). The mean (SD) plasma volume difference between two successive plasma volume measurements using indocyanine green was 38 (43) ml (r = 0.99). Plasma volume measured before and about 7 min after a hyperosmolar saline bolus (100 ml, 1 molar) was increased by 223 (102) ml and 286 (49) ml when determined by indocyanine green and plasma protein changes respectively. Nevertheless, the necessity for central venous injection and arterial sampling restricts the possible application of the method to intra operative or emergency care use. PMID- 8434748 TI - Development of a subdural motor blockade. AB - We report an unusual development of motor blockade following the subdural injection of local anaesthetic during attempted continuous lumbar epidural anaesthesia. Four characteristic features of subdural block, extensive spread, segmental distribution, delayed onset, and short duration of motor blockade were all features of the case. The patient had gradual development of complete motor blockade in the left upper extremity, incomplete in the right upper extremity, but absence of motor blockade in the lower extremities. The duration of complete motor blockade was 10 min in the hand and 35 min in the arm. The spread of contrast medium in the subdural space revealed the extent and degree of motor blockade. PMID- 8434749 TI - An evaluation of gastric emptying times in pregnancy and the puerperium. AB - In a controlled study, gastric emptying was measured during the three trimesters of pregnancy and after delivery, using an indirect paracetamol absorption technique. The peak plasma paracetamol concentration, time to reach the peak, and the area under the plasma paracetamol concentration-time curve, were determined. As compared to nonpregnant controls, there were no significant differences in the gastric emptying times of women in the three trimesters of pregnancy and of mothers from 18 h after delivery onwards. Gastric emptying was significantly delayed in mothers within 2 h after delivery (p < 0.01); median (range) values of peak paracetamol concentration, time to reach the peak and the area under the paracetamol concentration-time curve for this group were 12.5 (0.2-30.5) mg.l-1, 120 (30-120) min and 3.8 (0.1-16.6) mg.l-1 x h respectively, and 20.8 (8.6-64.5) mg.l-1, 40 (10-120) min and 13.5 (5.5-28.8) mg.l-1 x h respectively, for the nonpregnant control group (p < 0.01). Repeated measurements of gastric emptying in these women on the second postpartum day showed no significant delay. PMID- 8434750 TI - Prospective survey of the use of the laryngeal mask airway in 2359 patients. AB - Patients undergoing anaesthesia in which the laryngeal mask airway was used were prospectively audited over a 6-month period. A simple record sheet was completed at the time of anaesthetic administration and 2359 completed forms were analysed to assess problems encountered with its use. It was used successfully in 2350 patients (99.61%); of these, 1399 patients (59%) breathed spontaneously through the airway and 960 patients (41%) underwent intermittent positive pressure ventilation of the lungs. Two patients (0.08%) were reported to have regurgitated during the use of the laryngeal mask airway, but no serious sequelae associated with its use were encountered. PMID- 8434751 TI - Lignocaine spray applicators are a potential source of cross-infection in the anaesthetic room. AB - Ten percent lignocaine spray is in widespread clinical use as a means of suppressing responses to tracheal intubation. It is sprayed from a multidose container into the glottis and on to the vocal cords through an applicator nozzle, which may be used on successive patients. We have investigated the likelihood of the contamination of these nozzles, with patients' mouth flora. Spray applicators from four of the 20 cases investigated showed contamination with potential bacterial pathogens. We therefore recommend that lignocaine spray should not be applied to successive patients using the same applicator nozzle. PMID- 8434752 TI - Current practice of epidural analgesia during normal labour. A survey of maternity units in the United Kingdom. AB - A postal survey of all maternity units in the United Kingdom was conducted to gain information regarding policies for epidural analgesia for labour. The average epidural rate was 19.7% and 78% of units offered a 24-h service. The majority of units inserted the epidural with the patient in the lateral position, using a midline approach, with loss of resistance to air and saline being used almost equally. Most units used 3 ml of 0.5% bupivacaine as a test dose, and only 10% of units used adrenaline in the test dose. The use of adrenaline in subsequent top-ups was infrequent. Bupivacaine 0.5% was used most frequently for the initial and the second stage top-up, whereas 0.25% was most often used during the first stage of labour. Midwife top-ups were allowed in 75% of units and in only 14% of cases was this from a local anaesthetic reservoir. Epidural analgesia using a continuous infusion of anaesthetic was routinely used in 28% of units, mostly with 0.125% bupivacaine; about half of these units did so because midwives were unable to perform top-ups. Routine use of epidural opioids was most frequent when anaesthetic infusions were used, otherwise it was uncommon. PMID- 8434753 TI - Incidence and magnitude of hypoxaemia with ketamine in a rural African hospital. AB - The incidence of hypoxaemia with ketamine anaesthesia in unpremedicated, spontaneously breathing patients without oxygen supplementation at high altitudes has never been investigated. Twenty-three consenting patients received ketamine (2 mg.kg-1 intravenously in adults or 8 mg.kg-1 intramuscularly in children supplemented with 0.5 mg.kg-1 intravenously when clinically indicated) as the sole anaesthetic agent in a small, rural hospital in central Kenya (altitude 6000 ft; PIO2 127 mmHg). Oxygen saturation (SpO2) was measured with pulse oximetry. The SpO2 values were grouped in time epochs of pre-induction, postinduction but presurgery, every 1-2 min after start of surgery, and at the end of the case. The mean SpO2 values reached 90.8% during the first min following start of surgery and this was significantly different from pre-induction levels (p < 0.01). In four patients (17%) SpO2 decreased to 90% or less, in two patients (9%) SpO2 decreased to 85% or less, and in two patients (9%) SpO2 decreased to 75% or less. Mean values returned to near baseline by the end of the surgery. It is concluded that ketamine anaesthesia is acceptable in this setting if monitored by vigilant personnel who are capable of providing supplemental oxygen (if available) and manual support of the airway (i.e. jaw thrust) if airway obstruction occurs. PMID- 8434754 TI - Anaesthetic log books. How are they being used? AB - Since 1989, the Royal College of Anaesthetists has encouraged trainees to keep log books, although there is little information about the benefits of this practice as a part of anaesthetic training. A postal survey of all grades of trainee anaesthetist in the North West Region of England was conducted to obtain information about the present use of log books. The survey showed that log books are only used diligently by the more junior grades of anaesthetic staff. Although the practice of keeping a log resulted in an increased ability of the trainee to describe his clinical experience, the subsequent exploitation of this information to monitor or correct deficiencies in training was disappointingly low. PMID- 8434755 TI - Estimation of the correct length of tracheal tubes in adults. AB - Estimation of the correct length of a tracheal tube is extremely important and should be tailored to the needs of the individual patient. One hundred and eight patients who required tracheal intubation during anaesthesia were studied. The predicted length was estimated in each patient before induction of anaesthesia. The upper end of the cuff was aligned externally with the cricoid cartilage, while the more proximal part of the tube lay alongside the neck to the angle of the mandible. The tube was then curved forwards towards the upper incisor teeth, and the length at the teeth or gums was noted. The anaesthetist, who was unaware of the predicted length, intubated the trachea after induction of anaesthesia. The length of tube inserted was standardised in relation to the vocal cords, and the actual length of tube inserted was recorded. The estimated length was within 1.0 cm and 1.5 cm of the actual length in 91% and 97% of patients respectively. PMID- 8434756 TI - Routine pre-oxygenation. PMID- 8434757 TI - The haemodynamic effects of dopexamine infusion in the critically ill. PMID- 8434758 TI - Infusion charts for inotropes. PMID- 8434759 TI - Insertion of the laryngeal mask airway--not facilitated by cuff inflation. PMID- 8434760 TI - Split laryngeal mask airway as an aid to fibreoptic intubation. PMID- 8434761 TI - Inspiratory muscle effort during nasal intermittent positive pressure ventilation in patients with chronic obstructive airways disease. AB - Effective intermittent positive pressure ventilation can be achieved noninvasively using a nasal mask, but patient comfort may be compromised and respiratory effort increased unless the trigger threshold is low and the response time of the ventilator short. The effect of nasal ventilation upon inspiratory muscle effort and the functional characteristics of the trigger of a purpose built ventilator were evaluated in five patients with chronic obstructive airways disease. A measure of inspiratory muscle effort, the average pressure time integral per minute, decreased by at least 80% in four patients and by 50% in one. Only two patients had significant numbers of triggered breaths (17% and 47% of total) during 1 h of ventilation with settings as used at home. Therefore trigger function was evaluated when the patients were made to trigger the ventilator by slowing the control rate. A high resting end-expiratory intrathoracic pressure decreased the effective trigger sensitivity so that a mean (SD) change in oesophageal pressure of 14.8 cmH2O was required to lower mask pressure by 2.4 (0.3) cmH2O and activate the trigger. Even under these conditions of lowest trigger sensitivity inspiratory muscle effort was not increased compared to spontaneous ventilation. PMID- 8434762 TI - A 'skid' for easier insertion of the laryngeal mask airway. PMID- 8434763 TI - Laryngeal mask and tracheal stenosis. PMID- 8434764 TI - Convulsions following ketamine and atropine. PMID- 8434765 TI - Rationalising venous cannulation: patient factors and lignocaine efficacy. PMID- 8434766 TI - A modified bonded strain gauge for adductor pollicis mechanomyography. PMID- 8434767 TI - Accelerating CSF flashback in 29 gauge needles. PMID- 8434768 TI - Rebreathing and semiclosed anaesthetic breathing systems. PMID- 8434769 TI - Pulse oximetry artifact in a patient with a right ventricular myxoma. PMID- 8434770 TI - Anaesthetic machine checks during anaesthesia. PMID- 8434771 TI - A sticking valve. PMID- 8434772 TI - Nurse-call button on a patient-controlled analgesia pump? PMID- 8434773 TI - Ventilator pressure alarm line adaptor for the Penlon 200 fitted with a Newton valve. PMID- 8434774 TI - A problem with a 32-gauge spinal catheter. PMID- 8434775 TI - Gastro-oesophageal reflux and hiccup during anaesthesia. PMID- 8434776 TI - Continuous paravertebral block in children. PMID- 8434777 TI - Preparation of nuclear transplant embryos by electroportation. PMID- 8434778 TI - Lipoprotein oxidation and measurement of thiobarbituric acid reacting substances formation in a single microtiter plate: its use for evaluation of antioxidants. AB - Transition metals catalyze free radical-mediated oxidation of lipids and lipoproteins. This process is currently studied because of its potential relevance to pathological processes like atherosclerosis. Formation of thiobarbituric acid-reacting substances from polyenoic fatty acids is frequently used to follow oxidation of lipids and plasma lipoproteins. We describe here how Cu(II)- and Fe(III)-catalyzed oxidation of human low density lipoprotein or soy bean phospholipids and the photometric evaluation of the thiobarbituric acid reaching substances formed can be conducted in the same 96-well microtiter plate. The procedure showed a correlation of 0.98 with conventional two-stage fluorimetric and spectrophotometric methods and also showed better reproducibility. The plate method can handle up to one plate per hour with considerably less labor than the test tube assays. The plate procedure required small volumes of diluted samples of lipoproteins lipids and reagents. The method was suitable for testing the concentration-dependent antioxidant potency of substances like probucol, butylated hydroxytoluene, and alpha-tocopherol. The method can also be used to follow the kinetics of oxidation of lipoproteins. PMID- 8434779 TI - Quantitative polymerase chain reaction by monitoring enzymatic activity of DNA polymerase. AB - Nucleic acid amplification by polymerase chain reaction (PCR) is a very powerful technique in terms of sensitivity but is limited in terms of ability to perform accurate quantitation. While there is a theoretical correlation between copies of input target sequence and those of PCR product, the quantitative nature of this relationship is obscured by unpredictable variations in reaction conditions and by inhibitory and/or stimulatory substances which might be present in sample preparations, especially those derived from biological fluids. To reliably estimate copies of input DNA target from PCR product, we designed a combination of internal and external control systems coupled to DNA/RNA hybridization and enzymatic immunodetection techniques. The internal control system served to monitor amplification efficiency and to correct for the effects of inhibitors or stimuli on the efficiency of the DNA amplification. The assay is quantitative, nonisotopic, and can be widely applied to assessment of the quantity of DNA present in a wide range of preparations. PMID- 8434780 TI - Use of Fourier transform infrared spectroscopy for the simultaneous quantitative detection of metal carbonyl tracers suitable for multilabel immunoassays. AB - We describe here a new approach for multilabel immunoassays. The starting point of this approach is a new nonradioisotopic immunoassay (carbonyl metallo immunoassay) based on the use of metal carbonyl complexes as tracers and Fourier transform infrared (FT-ir) spectroscopy as the detection method. We show here that the judicious choice of the organometallic tracers associated with multicomponent analysis of FT-ir spectroscopic data provides the simultaneous rapid and reliable quantitation of pmol of the organometallic tracers. The feasibility of this approach is demonstrated in the case of the two major antiepileptic drugs phenobarbital and carbamazepine. PMID- 8434781 TI - Nondestructive detection of gangliosides with lipophilic fluorochromes and their employment for preparative high-performance thin-layer chromatography. AB - A simple and effective procedure for the isolation and purification of gangliosides by preparative thin-layer chromatography is described. The method is based on nondestructive visualization of gangliosides on silica gel-precoated thin-layer chromatography plates by staining with uncharged lipophilic fluorochromes. Fluorescent dyes were added in low concentrations into the mobile phase (0.002%, w/v) without any interference of the ganglioside separation. After uv localization, the fluorescent zones were scraped off the plate and the silica gel was extracted with chloroform/methanol/water (30/60/8). In the following step fluorochromes were removed from gangliosides containing crude extracts by anion exchange chromatography on DEAE-Sepharose. After desalting, impurities were removed by Iatrobeads chromatography. The method described offers an easy to handle and successful preparative thin-layer chromatography strategy to obtain pure gangliosides in microgram and miligram quantities. PMID- 8434782 TI - Analysis of thermally induced protein folding/unfolding transitions using free solution capillary electrophoresis. AB - It is shown that free solution capillary electrophoresis (FSCE) can be used to monitor the temperature-dependent folding/unfolding transitions of proteins. Furthermore, analysis of the data obtained by FSCE can be used to estimate the apparent thermodynamic parameters (enthalpy change (delta HvH), entropy change (delta S), and transition temperature (Tm)) associated with the folding/unfolding transition. In addition to mobility changes associated with the transition, FSCE analysis is unique in its ability to provide access to the population distribution of mobility states. This is demonstrated by the temperature dependent change in the electrophoretic peak width and by the appearance of multiple peaks for very slow equilibrium or irreversible processes. Moreover, by comparing the mobility of the denatured state to that of unstructured model peptides, it is possible to characterize the relative degree of structure present in the unfolded state of a protein. This methodology has been applied to the analysis of the thermally induced unfolding of lysozyme at low pH. It is shown that the mobility of thermally denatured lysozyme can be described by the same function that describes unstructured, fully solvated peptides. On the contrary, the mobility of the native lysozyme is significantly higher than the value predicted by the same function. The accuracy of the apparent thermodynamic parameters obtained by this methodology compare within error with values obtained by direct calorimetric measurements using differential scanning calorimetry. PMID- 8434783 TI - Error analysis in manual and automated DNA sequencing. AB - The frequency, position, and type of errors were analyzed for sequence data which were generated with the help of (I) a manual digitizer, (II) an off-line automated film reader, and (III) an on-line automated gel reader. About 400 film/gel readings were analyzed and the results were used to generate error profiles for each method. The profiles identify several method- and project specific problem areas and provide useful guidance for the assessment of DNA sequence data in general. PMID- 8434784 TI - Synthesis and characterization of the selenium analog of glutathione disulfide. AB - We synthesized the selenium analog of glutathione disulfide by a liquid phase method and named it glutaselenone (i.e., gamma-L-glutamyl-L selenocysteinylglycine) diselenide. The selenol of selenocysteine was protected by the p-methoxybenzyl group, which was removed by acidolysis with trifluoroacetic acid in the presence of thioanisol. The overall yield of the final product, glutaselenone diselenide, was about 9% based on the starting compound, Se-(p-methoxybenzyl)-L-selenocysteine. Glutaselenone diselenide showed a broad absorption band between 270 and 400 nm and circular dichroism bands around 270 nm (positive) and 330 nm (negative), which were attributable to diselenide bond. PMID- 8434785 TI - Gas chromatographic-mass spectrometric assay of tissue malondialdehyde, 4 hydroxynonenal, and other aldehydes after their reduction to stable alcohols. AB - Measurement of specific aldehydes such as malondialdehyde, hexanal, or 4 hydroxynonenal provides a method to evaluate the extent of lipid peroxidation. However, assay of aldehydes is complicated by their high reactivity toward other molecules and their chemical instability. In the proposed method, aldehydes are reduced to stable alcohols. Except for malondialdehyde, this is readily accomplished under neutral conditions at room temperature or at 4 degrees C with either sodium borodeuteride (NaB2H4) or sodium borohydride (NaBH4). Complete reduction of malondialdehyde requires a more powerful reducing agent, borane trimethylamine. After ether extraction and evaporation of the organic phase, the alcohols are converted to t-butyldimethylsilyl ethers and analyzed by selected ion monitoring gas chromatography-mass spectrometry in the positive chemical ionization mode for malondialdehyde and 4-hydroxynonenal and electron impact mode for all other aldehydes. Quantitation is achieved using internal standards of 1,3 [2H8]propanediol for MDA, of 4-[2-2H]hydroxynonenal for 4-hydroxynonenal, and of the corresponding saturated per-deuterated alcohols for all saturated aldehydes, for example and [2H13]hexanol for hexanal. Saturated per-deuterated alcohols also serve as external standards for their unsaturated aldehydes with same chain length. The detection limit for individual aldehydes is 0.5 nmol in a given sample. In addition to being highly sensitive and selective, the present method allows one to verify the identity of each aldehyde by observing a mass shift when aldehydes are reduced with either NaB2H4 or NaBH4. The usefulness of our method is demonstrated by measuring aldehyde accumulation in autoxidized arachidonic acid solutions and in heart homogenates before and after induction of peroxidation. PMID- 8434786 TI - Determination of the distribution of selenium between glutathione peroxidase, selenoprotein P, and albumin in plasma. AB - A chromatographic method is described to determine the distribution of selenium between selenoprotein P, glutathione peroxidase (GSH-Px), and albumin in plasma, using two small columns of heparin-Sepharose and reactive blue 2-Sepharose linked together in tandem. One milliliter of plasma was diluted to 12 ml with 0.02 M sodium phosphate buffer, pH 7.0 (the equilibration buffer), applied to the heparin-Sepharose column, and eluted at a flow rate of 30 ml per hour. GSH-Px was not retained by either of these columns but selenoprotein P was retained by heparin-Sepharose and albumin by reactive blue. After the two columns were separated, selenoprotein P was eluted with heparin from heparin-Sepharose and albumin eluted from reactive blue with high salt. Analytical work confirmed the presence of selenoprotein P, GSH-Px, and albumin in the respective fractions. When rats were injected with 75Se as either selenite or selenomethionine most of the radioactivity was incorporated into the selenoprotein P fraction, with the next greatest amount into GSH-Px, and the least amount into albumin. Slab gel electrophoresis was used to determine that most of the selenium in each of the three fractions was associated with each of these selenium containing proteins. This method indicated that the majority of the selenium in plasma is associated with selenoprotein P, and the only time this was found not to be true was with high levels of dietary selenomethionine. PMID- 8434787 TI - Rapid and simultaneous determination of monoamine oxidase A and monoamine oxidase B activities in mouse brain homogenates by liquid chromatography with electrochemical detection. AB - Sensitive and rapid enzymatic assays have been developed and optimized to measure the separate and combined activities of monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) in mouse brain tissue homogenates using liquid chromatography with electrochemical detection (LCEC). The selectivity for the two isozymes is primarily afforded by use of selective substrates, 5-hydroxytryptamine (5-HT) for MAO-A and 3-methoxy-4-hydroxybenzylamine (MHBA) for MAO-B. The selectivity of the separate assays is further enhanced by the use of inhibitors, deprenyl to block MAO-B and clorgyline to block MAO-A. The dual assay procedure, which employs no inhibitors, shows remarkably enhanced selectivity for each of the isozymes through the use of the two substrates; the preferred substrate for one isozyme acts as an effective competitive inhibitor of the nontargeted substrate for that isozyme, leading to substantially decreased activity for the latter substrate. Using the dual assay, kinetic constants determined for MAO-A (mean +/- SD) were: Km,5-HT = 39 +/- 7 microM, Vmax,5-HT = 37.6 +/- 2.1 pmol/mg wet tissue/min, Km,MHBA = 341 +/- 75 microM, and Vmax,MHBA = 27.7 +/- 2.3 pmol/mg wet tissue/min; those for MAO-B were: Km,MHBA = 108 +/- 11 microM, Vmax,MHBA = 44.3 +/- 1.2 pmol/mg wet tissue/min, Km,5-HT = 1704 +/- 122 microM, and Vmax,5-HT = 12.0 +/- 0.3 pmol/mg wet tissue/min. The separate isozyme procedures, when used without selective inhibitors, reflect only 88.3% of the MAO-A activity using the 5-HT velocity and only 66.0% of the MAO-B activity using the MHBA velocity. On the other hand, when the dual assay is employed, 98% of the observed 5-HT velocity can be directly attributed to MAO-A, and 94% of the observed MHBA velocity can be directly attributed to MAO-B. The dual assay was employed to demonstrate the relative change in the activity of these two enzymes in whole mouse brain between 27 and 74 days of age. During this time, the MAO-B activity increased from approximately 40 to approximately 60% of the total MAO activity. Under typical conditions, results can be easily obtained from any of the three procedures outlined for 100 samples in less than 2 working days, including only 3.5 h for the LCEC portion. PMID- 8434788 TI - Fabrication of surfaces resistant to protein adsorption and application to two dimensional protein patterning. AB - Proteins were attached in defined geometric patterns on a surface. A prerequisite to making a pattern of proteins is generation of surfaces resistant to nonspecific protein adsorption. This was accomplished via oxidation of the thiol terminus of an organosilane self-assembled monolayer film by deep ultraviolet (DUV) irradiation. The resultant surface exhibited marked resistance to protein adsorption. Using a mask to protect regions of the silanized surface from irradiation, proteins were selectively adsorbed or attached via covalent linkage at locations protected from the DUV light. Antibodies immobilized in patterns using this procedure retained their antigen-binding capability. Thus chemistry and DUV lithography were combined to create patterns of active biomolecules which could be used in the microfabrication of electronic devices and biosensors. PMID- 8434789 TI - High-performance cation-exchange chromatography of hexosaminitols. PMID- 8434790 TI - An ultrarapid method for the recovery of DNA from gels. PMID- 8434791 TI - Dithiothreitol improves the efficiency of yeast transformation. PMID- 8434792 TI - High resolution fractionation and characterization of ADP-ribose polymers. AB - Methods are described for the high resolution fractionation and characterization of ADP-ribose polymers. Polymers prepared in vitro using purified poly(ADP ribose) polymerase were isolated free from interfering nucleic acids and salts using dihydroxyboronyl-Bio-Rex 70 chromatography and fractionated using anion exchange high-pressure liquid chromatography. The homogeneity of isolated polymer fractions was characterized by gel electrophoresis and polymer size was determined by analysis following enzymatic digestion to nucleosides. The method allows isolation of oligomers up to 50 mer as single species and larger polymers can be isolated free from oligomers according to size and branching frequency. The ability to isolate individual species of ADP-ribose polymers should prove useful for the study of the polymers and their noncovalent interactions with other components of chromatin. Microheterogeneity of individual oligomers was studied and shown to be due to differences at the protein proximal ends resulting from the chemical method of release of polymers from protein. The method also was applied to fractionate polymers generated in intact cultured mouse cells in response to treatment with the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine. PMID- 8434793 TI - Application of oxime formation in a radiometric assay of aminooxy compounds. AB - A radiometric determination of monoaminooxy analogues of naturally occurring polyamines is described in which [2-14C]acetone is employed as reagent. The reagent is volatile while the oxime product is not allowing unreacted reagent to be removed and the oxime formation to be completed by lyophilization in vacuo. The residual radioactive compound is soluble in water and proportional to the reactive aminooxy content of the reaction mixture and can be quantified by liquid scintillation counting. The assay method is inexpensive and simple and has high specificity and flexibility in sample volume enabling reliable quantification of reactive aminooxy amines in biological extracts at concentrations exceeding 0.25 microM. Optimal pH values for oxime formation of five monoaminooxy analogues of polyamines with acetone were resolved. Reactions via reversible intermediates to irreversible oximes were sped up by removal of water. Complete oxime formation and stability was confirmed by 1H NMR studies. Tested drugs readily formed oximes with pyridoxal 5'-phosphate, too. Diaminooxy analogue of cadaverine formed a volatile oxime with acetone. The method was used to monitor the stability of aminooxy analogues of putrescine and spermidine during storage and under culture conditions and to establish their scant accumulation in, but fast catabolism by, cultured baby hamster kidney cells. PMID- 8434794 TI - Comparison of the Lowry and the Bradford protein assays as applied for protein estimation of membrane-containing fractions. AB - Although the Bradford protein estimation assay has found wide distribution, it has a number of drawbacks, which in some cases have been shown to produce erroneous results upon comparison to other, more precise, methods for protein estimation. It was found that the underestimation of the protein content of membrane-containing fractions cannot be overcome by pretreatment with NaOH or the detergents employed (Triton X-100, sodium dodecyl sulfate, 3[(3-cholamidopropyl) dimethylammonio]propanesulfonic acid) and the protein estimates obtained do not agree with estimates obtained by the Lowry assay. Upon storage of fractions at 20 degrees C there is a considerable loss of dye binding activity, varying in accordance with the membrane content of the fractions, reaching up to 58% in the case of membrane-enriched fractions stored at -20 degrees C for 15 days. Pretreatment with the employed agents brought about an equal increase of dye binding capacity, specific for the individual fractions; however, none of these agents could recover the dye binding activity lost during several days of storage at -20 degrees C. It is suggested that the straightforward Bradford procedure has a rather limited scope of application, particularly concerning membrane containing samples, and requires preliminary studies to determine its applicability according to the nature of the biological material examined. PMID- 8434795 TI - Molecular analysis of lipid macroamphiphiles by hydrophobic interaction chromatography, exemplified with lipoteichoic acids. AB - Analyzed were (I) the oligoglucosyl-, alanyl-substituted poly(glycerophosphate) lipoteichoic acid of Enterococcus hirae containing Glc(alpha 1-2)Glc(alpha 1 3)acyl2-Gro and a phosphatidyl derivative thereof as lipid anchor, (II) the poly(digalactosyl, galactosylglycerophosphate) lipoteichoic acid of Lactococcus garvieae containing the same glycolipid and an acyl derivative of it, and (III) the N-acetylglucosaminyl-, alanyl-substituted poly(glycerophosphate)lipoteichoic acid of Staphylococcus aureus with Glc(beta 1-6)Glc(beta 1-3)acyl2Gro as the sole lipid moiety. Hydrophobic interaction chromatography on octyl-Sepharose separated lipoteichoic acids I and II into two peaks according to the number of fatty acids. Within each peak further fractionation occurred in the order of decreasing length of the hydrophilic chain. A similar fractionation was observed within the single peak of lipoteichoic acid III. With lipoteichoic acid I and III the extent of glycosylation decreased with decreasing length of the hydrophilic chain whereas the content of alanine ester remained either constant or increased. Variations in the oligosaccharide pattern of lipoteichoic acid I and in the fatty acid composition of all lipoteichoic acids could also be observed. Collectively, the data provide for the first time a detailed picture of the complex polydispersity of lipoteichoic acids comprising the number of fatty acids, the length of the hydrophilic chain, the kind and extent of chain substitution, and the fatty acid composition. The procedure will also be applicable to the molecular analysis of lipopolysaccharides and bacterial lipoglycans. Moreover, the results are of physicochemical interest because they demonstrate for lipid macroamphiphiles an inverse relationship between hydrophobicity and the size of the hydrophilic headgroup. PMID- 8434796 TI - Molecular analysis of the lipoglycans of Mycobacterium tuberculosis. AB - Lipoglycans were extracted from disrupted cells of Mycobacterium tuberculosis with hot phenol-water. Hydrophobic interaction chromatography on octyl-Sepharose of the crude extract separated nucleic acids and lipoglycans. The latter were retained on the column and fractionated on elution with a propanol gradient into six peaks primarily according to decreasing size of the hydrophilic head groups which dropped from 70 to 5 or 4 monosaccharide residues per molecule. The number of fatty acids per molecule rose from 2.1 to 3.4 over the elution profile, suggesting species containing two, three, and four fatty acids. Peaks I and II and peaks III and IV represented two pairs of lipoarabinomannan and lipomannan, those of peak III and IV containing as a whole smaller hydrophilic head groups and more fatty acids. Peak V and VI are reminiscent of the oligomannosyl derivatives of phosphatidylinositol discovered earlier in mycobacteria. The lipid anchor of all molecular species was shown to be phosphatidylinositol with the extra acyl groups not yet localized. This and an accompanying report complement each other in demonstrating the potential of hydrophobic interaction chromatography for molecular analysis of lipid macroamphiphiles. Lipoteichoic acids, due to continuous small variations in the size of their hydrophilic head groups, separate primarily according to the number of fatty acids, whereas mycobacterial lipoarabinomannans, lipomannans, and phosphatidylinositol mannosides differ as entities so greatly in the size of the hydrophilic headgroup that this quality becomes predominant for separation. PMID- 8434797 TI - Analysis of the inversion effect in pulsed field gel electrophoresis by a two dimensional contour-clamped homogeneous electric field system. AB - A two-dimensional contour-clamped homogeneous electric field electrophoresis was used for the separation of the yeast Saccharomyces cerevisiae chromosomes. The role of different pulse times and field strengths was examined. The resulting complex migration curves were similar to those predicted by the bag model. They are characterized by a straight line in the region of lower molecular weight where the migration is inversely proportional to the molecular weight and a mobility inversion in the region of higher molecular weight both depending on the conditions chosen for the two directions. The quantitative analysis of the data was compared with the predictions of the bag model which is shown to be a good approximation. Using this experimental approach the separation pattern of a commercially available S. cerevisiae standard was examined under standard electrophoresis conditions, and chromosomes IV and XII were found to be inverted. PMID- 8434798 TI - Detection and quantification of N-acetyl-beta-D-glucosaminidase, chitobiosidase, and endochitinase in solutions and on gels. AB - Procedures are described for the direct assay of N-acetyl-beta-glucosaminidase (EC 3.2.1.30), chitobiosidase, and endochitinase (EC 3.2.1.14) after separation on starch or polyacrylamide electrophoresis gels. The enzymes were visualized as fluorescent bands by using an agarose overlay containing 4-methylumbelliferyl derivatives of N-acetyl-beta-D-glucosaminide, beta-D-N,N'-di-acetylchitobioside, or beta-D-N,N',N"-triacetylchitotriose for N-acetyl-beta-glucosaminidase, chitobiosidase, or endochitinase, respectively. For quantitative assay of N acetyl-beta-glucosaminidase and chitobiosidase in solutions, a rapid technique using nitrophenyl-N-acetyl-beta-D-glucosaminide and nitrophenyl-beta-D-N,N' diacetyl-chitobiose, respectively, was used. Endochitinase activity was quantitatively measured by determining the percentage reduction in turbidity of a reaction mixture that contained purified colloidal chitin. Trichoderma harzianum strain P1 was shown to produce three kinds of chitinolytic enzymes, and there were multiple forms of some of these. PMID- 8434799 TI - Rapid diffusion coefficient measurements using analytical SPLITT fractionation: application to proteins. AB - This work reports a new technique for the rapid measurement of diffusion coefficients using a special flow cell called a SPLITT cell. Such SPLITT cells, designed for continuous SPLITT fractionation, utilize differential transport across a thin (approximately 100 microns) ribbonlike lamina flowing through the cell. The liquid stream in the cell is split into two substreams at the outlet. The relative concentration in the two outlet substreams of a dilute component introduced into one of two inlet substreams is mathematically related to the appropriate transport coefficient, in this case the diffusion coefficient D. Thus D can be calculated from measured values of relative outlet concentrations. This approach has been tested using a number of dilute protein solutions. The results at different stream-splitting ratios are reasonably self-consistent and agree with most literature values for D within 5%. This approach provides a simple, rapid, and predictable means for determining the diffusion coefficients of proteins and other substances. PMID- 8434800 TI - Linked functions and the analysis of individual-site binding data. AB - Linked ligand functions for analyzing experimental data evaluated to yield macroscopic apparent binding constants were well developed by Adair and by Wyman. In this paper, expressions for the linked function (derivative) delta ln(K)/delta ln(c) are applied to both macroscopic association constants and individual-site association constants derived from individual-site binding data. A detailed treatment of a simple interacting system is presented. We demonstrate that data from individual-site isotherms can be interpreted only after explicit assumptions specifying the nature of the ligand-dependent interactions are made. PMID- 8434801 TI - Two-dimensional elution map of GalNAc-containing N-linked oligosaccharides. AB - We have previously published a two-dimensional (2-D) mapping technique for N linked oligosaccharides using pyridylaminated derivatives (PA-oligosaccharides) (N. Tomiya et al. Anal. Biochem. 171, 73-90, 1988). We now report an extension of this method to GalNAc-containing N-linked oligosaccharides. The new 2-D map was prepared from the elution data of 40 different GalNAc-containing oligosaccharides, 16 of which were obtained directly from human urinary kallidinogenase by digestion with glycopeptidase A. The other 24 oligosaccharides were derived by subsequent digestion of the 16 original oligosaccharides with beta-galactosidase or alpha-fucosidase. Each of the 40 oligosaccharide derivatives was separated by high-performance liquid chromatography using ODS silica and amide-silica columns. The 2-D map constructed by plotting elution position of each oligosaccharide (expressed in terms of glucose units) can be useful as such in delineating the structure of an unknown oligosaccharide by direct placement of its elution positions in the 2-D map. Multiple regression analysis of the data as performed previously yielded parameters related to the contribution of each component monosaccharide unit to the elution profile. The best results were obtained when the GalNAc-containing PA-oligosaccharides were classified into an F-series (those containing Fuc alpha 6GlcNAc-PA) and a Z series (all others), based on our previous classification method. These calculated values are useful in predicting oligosaccharide structure from known elution values as well as to predict elution volumn from a known structure. The structure of a minor GalNAc-containing oligosaccharide in human urinary kallidinogenase was elucidated using these newly calculated values. PMID- 8434802 TI - Effects of aging and hematocrit on cerebral blood flow velocity in patients with unilateral cerebral infarctions: a Doppler ultrasound evaluation. AB - By means of conventional continuous-wave (CW) (4 MHz) and transcranial pulsed (2 MHz) Doppler sonography 50 patients (34 men and 16 women, mean age 58.6 +/- 7.6 years) who survived unilateral cerebral infarctions (UCI) in the middle cerebral artery (MCA) territory were investigated. The control group consisted of 30 presumed healthy age-matched persons. The main quantitative sonographic parameters of the major arteries of the head and the basal cerebral arteries were evaluated. On the day of the neurosonographic investigations, hematocrit (Hct) was determined. Low-degree stenoses of the internal carotid arteries were found in 26 (52%) of the patients. Increased intracranial vessels' resistance in the MCA on the infarction side was usually obtained. Decreasing of Doppler shift frequency with advancing age and increasing of Hct was established in the controls. In patients with UCI the effects of aging and Hct on the sonographic parameters of the collateral arteries were more pronounced. Obviously, in patients with UCI, the alterations of the sonographic parameters are caused by parallel influence of vessels' disease, age-defined changes of vessels' walls, and viscosity variations. PMID- 8434803 TI - Increased risk of coronary artery dissection during coronary angiography with 6F catheters. AB - The use of smaller sized catheters for coronary angiography (CA) is increasing, but little is known about the safety of CA with 6F catheters. The authors reviewed all cases of CA in which 6F and 8F catheters were used in adult patients between 1988 and June, 1990. There were 597 patients in the 6F group and 2,409 patients in the 8F group. Cases of CA with 6F catheters were more likely to be elective (95% vs 87%), to have no coronary disease (35% vs 24%), and to be performed by nonfirst-year fellows (70% vs 54%) when compared with CA with 8F catheters. There were 5 cases of coronary artery dissection. The incidence of dissections was significantly higher (p = .007) in the 6F group (0.67%) than in the 8F group (0.04%). The incidence of dissections was highest for first-year fellows using 6F catheters (1.7%), which was significantly higher (p = .008) than for first-year fellows using 8F catheters. The incidence of major vascular complications tended to be lower (p = .068) in the 6F group (0.17%) than in the 8F group (0.95%). In summary, CA with 6F catheters is associated with an increased risk of coronary artery dissection, particularly with less experienced operators, but tends to be associated with a lower risk of major vascular complications. PMID- 8434804 TI - Combined effects of urokinase and heparin on PTT values during thrombolytic therapy. AB - The local infusion of urokinase may be complicated by hemorrhage. Except for maintaining fibrinogen levels above 100 mg/dL, no other criteria exist for titrating the dose of urokinase to avoid hemorrhagic complications. A retrospective examination of the fibrinolytic and coagulation states was performed on 11 patients receiving local high-dose urokinase (240,000 U/hr) and heparin for thrombolysis of acute occlusions to identify parameters other than fibrinogen levels that may correlate with bleeding complications. Five patients experienced bleeding complications, 3 of whom had partial thromboplastin time (PTT) values greater than 150 seconds. None of the five patients having hemorrhagic complications had fibrinogen levels below 100 mg/dL at any time. Urokinase began to enhance the effect of heparin on PTT values as a result of reducing fibrinogen levels. In 10 of 11 patients this effect caused PTT values to at least double when compared with heparin alone. This substantial rise in PTT occurred only after fibrinogen levels approached 200 mg/dL in 8 of 11 patients. Although the number of patients is small, these data suggest that when heparin is used during thrombolysis, closer PTT monitoring should be carried out as fibrinogen levels begin to decline, especially when they approach 200 mg/dL, to avoid excessive PTT elevations and subsequent bleeding. PMID- 8434805 TI - New prospects for the treatment of Raynaud's phenomenon using a serotoninergic S2 receptor antagonist (ketanserin) and stable derivatives of prostacyclin. AB - The authors propose a promising new therapy for the treatment of Raynaud's phenomenon, with parenteral prostacyclin (carbaprostacyclin) and a serotonergic S2-receptor antagonist (ketanserin) given orally. They studied 31 patients, 22 treated with ketanserin and carbaprostacyclin, 9 with carbaprostacyclin alone. Both groups demonstrated successful results and a significant improvement in measurements performed by photoplethysmography and transcutaneous pulse oximetry. PMID- 8434806 TI - Effects of lovastatin on high-density lipoprotein subfractions in hypercholesterolemic patients with peripheral vascular disease. AB - The effects of lovastatin treatment on high-density lipoprotein subfractions (HDL2 and HLD3) were investigated in 34 patients with severe peripheral vascular disease and type IIa or type IIb hyperlipoproteinemia by use of a density gradient ultracentrifugation method. Lovastatin therapy caused greater percentage changes in HDL2 than in HDL3. In HDL2 the increases of cholesterol, total lipid, apolipoprotein AI (apoAI) and apolipoprotein AII (apoAII) concentrations were 23% (p < 0.05), 28% (p < 0.01), 24% (p < 0.01) and 11% (p < 0.01), respectively, in subjects with the type IIa phenotype. In patients with the type IIb phenotype the corresponding increases were 42% (p < 0.01), 44% (p < 0.01), 38% (p < 0.01) and 21% (p < 0.05), respectively. The apoAI/apoAII weight ratio in HDL2 rose by 11% and by 13% in type IIa and type IIb patients, respectively. The present results suggest that during lovastatin treatment the slight increase in serum HDL cholesterol concentration was due, not to cholesterol enrichment by high-density lipoproteins, but more probably to an increase of the number of HDL particles. The observed changes were more pronounced in type IIb than in type IIa patients. PMID- 8434807 TI - New approaches in the medical management of venous ulceration. AB - This literature survey of the medical treatment of venous ulcers of the lower extremities discusses five classes of agents: (1) fibrinolytics, (2) hydroxyrutosides, (3) prostaglandins, (4) methylxanthines, and (5) others. The authors conclude that all these agents require further research. PMID- 8434808 TI - Venous lower extremity ulcer: an underestimated disorder--new insights on its pathogenesis. PMID- 8434809 TI - Blood pressure and heart rate relationship in normotensive and hypertensive subjects. AB - A twenty-four-hour blood pressure (BP) monitoring was performed in 20 normotensive and 20 hypertensive subjects, matched by sex and age. Blood pressure and heart rate (HR) variability were evaluated both as absolute and percent standard deviation. In agreement with the literature no significant difference in HR and BP variability was observed between the two groups. The linear regression between HR and BP values was evaluated in both groups. The authors observed a significant difference in the relationship between these two cardiovascular variables between the two groups. In the hypertensive group the cardiovascular control of HR and BP showed a different relationship than in normotensive subjects, suggesting a different neurovegetative modulation. PMID- 8434810 TI - Acute fatality following pulmonary angiography in a patient on an amiodarone regimen--a case report. AB - A patient being treated with amiodarone experienced acute respiratory failure and death immediately following pulmonary angiography. Physicians must be aware of the potential catastrophic complication of both ionic and nonionic contrast angiography in this setting. PMID- 8434811 TI - Tricuspid valve thromboembolus with recurrent pulmonary embolism--a case report. AB - The authors describe a fifty-one-year-old man with multiple pulmonary emboli in whom two-dimensional echocardiography clearly showed a large mobile thrombus transiently entrapped in the chordal apparatus of the tricuspid valve, a location rarely noted except in autopsy specimens. Subsequent lung scan and echocardiograms documented clinically silent nonfatal embolization of this large thrombus to the lungs. Whereas most patients with this form of thromboembolic disease come to either surgery or autopsy, this case demonstrates how the combination of echocardiography and lung scanning can be used to differentiate the etiology of some right-heart masses. PMID- 8434812 TI - Case of fluoxetine-induced remission of Raynaud's phenomenon--a case report. PMID- 8434813 TI - Intracerebral hemorrhage associated with migrainous headache--a case report. AB - A case of intracerebral hemorrhage that developed some time after severe headache is reported in a relatively young woman. It is proposed that hemorrhage may also be included among the causes of so-called migraine-related stroke, which has generally been known to result from infarction. PMID- 8434814 TI - The risk of emergency intestinal bleeding among users of acenocoumarin: a population-based cohort study. AB - In spite of a 10-13 fold increased risk of bleeding, standard doses of coumarin with a target prothrombin time of 2.7-4.5 INR (International Normalized Ratio) are chronically used in the Netherlands by 4-5% of the adult population forty to eighty years old, mainly for the secondary prevention of myocardial infarction. The Dutch Thrombosis Services, who monitor these patients, use less rigorous criteria than the standard studies do. It would not, therefore, be too much of a surprise if the numbers of bleeding complications in practice would be much higher than expected from the standard papers so far. To answer this question the authors studied emergency intestinal bleedings in a population-based cohort study of chronic acenocoumarin users (813 person years) and their age-matched and population-based controls (17,620 person years). Of 142 first bleedings serious enough to require immediate sigmoidoscopy, 35 were connected with acenocoumarin (25%). The overall incidences in the acenocoumarin cohort and the age-matched controls were, respectively, 4.3 and 0.6 bleedings/100 person years, RR (relative risk) 7.09, p < 0.0001. Relative Risk (RR) = Incidence Among Exposed/Incidence Among Nonexposed The acenocoumarin bleeders and their controls had symmetric clinical diagnoses and levels of hemoglobin. However, acenocoumarin bleeders were significantly older and more frequently males. The sex- and age-adjusted RRs were, however, only slightly different from the crude data, suggesting no major influence of these asymmetries on the overall results. Prothrombin times in the acenocoumarin bleeders were frequently higher than the target range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8434815 TI - Noninvasive ultrasonic biopsy: evaluation of early arteriosclerotic lesions progression in normal asymptomatic, hyperlipidemic, and diabetic subjects. AB - Noninvasive ultrasonic biopsy (UB) is a method of detecting early arteriosclerotic changes by high-resolution ultrasound scanning of the carotid and femoral bifurcation. Six UB classes (scoring 0 to 10) have been identified in 2000 asymptomatic subjects and 600 vascular patients followed up for four years. The incidence of silent coronary ischemia (tested by effort test) and the occurrence of symptomatic events in four years are increased in advanced classes and with increasing UB score. The rate of progression (ROP) in four years to the next UB class has been defined in normal subjects (1.4% in class I, 3.1% in II, 10.7% in III, 17.9% in IV, and 79.2% in class V). In a group of 305 asymptomatic hyperlipidemic subjects and in a group of 269 diabetics the ROP (in four years) was significantly higher. Therefore ultrasonic biopsy is useful to identify subjects at risk of coronary ischemia and cardiovascular events and to follow up noninvasively the progression of arteriosclerosis. PMID- 8434816 TI - Effect of shear stress on 86Rb+ efflux from calf pulmonary artery endothelial cells. AB - The effect of flow-induced shear stress on membrane K+ permeability was investigated by measuring 86Rb+ efflux in cultured calf pulmonary artery endothelial cells. Cells were subjected to step changes in shear stress from 1 dyn/cm2 to 2.4, 4.8, or 10 dyn/cm2 in a parallel-plate flow chamber. Increasing shear stress produced a graded, transient increase in 86Rb+ efflux which peaked within 1 min and subsequently declined rapidly toward pre-stimulus levels. Upon returning shear stress to 1 dyn/cm2, 86Rb+ efflux initially decreased, but returned slowly to basal values. In contrast, application of bradykinin at a constant shear stress of 1 dyn/cm2 produced a transient increase in 86Rb+ efflux that was followed by a sustained elevated phase during which time efflux gradually returned to pre-stimulus levels. In order to exclude the possibility that the transient increase in 86Rb+ efflux with shear stress simply reflects a flow-dependent change in the washout of radiotracer, the transient convection diffusion equation was solved using finite element simulation. When the flux of 86Rb+ from the cell monolayer was assumed to be constant with time, the mathematical model predicted an increase in efflux rate coefficients upon step increases in flow that were only 7-19% of that observed experimentally. The numerical predictions correlated well with the experimentally obtained peaks when the flux of 86Rb+ from the cell monolayer was simultaneously increased with flow to a new steady value. These simulations however, could not predict the transient nature of the response to increased shear stress.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8434817 TI - Effects of defibrillation shock energy and timing on 3-D computer model of heart. AB - We present computer simulations of electrical defibrillation in a three dimensional model of the ventricles of the heart. In this model, called HEARTSIM, the ventricles are represented by 1473 cubic elements with 3 mm sides. The action potential is described by five discrete states; absolutely refractory, three relatively refractory, and repolarized. Activation is propagated to an element's six orthogonal neighbors with the conduction velocity dependent on the refractory state of the neighbor. Delivery of several extra-stimuli with decrementing coupling intervals results in ventricular fibrillation. Following the onset of ventricular fibrillation, we simulate defibrillation using various electrode configurations, shock energies, and timings. The current density distributions in the heart model resulting from the defibrillation shocks are determined from finite element analysis of the electric fields produced by the delivery of high energy shocks. The simulations suggest that successful defibrillation shocks produce a short period of low activation followed by a complete cessation of activation for a duration of 387 +/- 162 ms. In contrast, unsuccessful shocks produce a significantly shorter period of low activation (70 +/- 12 ms) after which ventricular fibrillation resumes. HEARTSIM mimics the experimentally reported, highly variable response to near-threshold shocks--the energy for successful defibrillation varies widely (20.8 +/- 20.7 J). In addition, the success rate vs. energy curve has a sigmoidal shape that is consistent with experiments. We demonstrate that this variability in the energy requirement results from dynamic variability in the number of elements made refractory by the shock and the relative distribution of the activation pattern at the time of the shock. Further, we show that it may be possible to lower the defibrillation energy requirements by delivery of two successive low energy pulses. The most efficient timing for the second pulse corresponds to the repolarization of the elements that were excited by the first pulse. Thus, when the interval between the two pulses was 85 +/- 18 ms, the defibrillation threshold energy (DFE) is reduced by 30.7 +/- 10% with pulses of 10 ms duration, and 62.6 +/- 7.9% with pulses of 5 ms duration. Our simulations also show that there is a delicate balance of energy between the two pulses that must be reached in order to achieve energy reduction with double pulse defibrillation. In conclusion, HEARTSIM serves as a tool for studying the underlying mechanisms of the effects of DF shocks on ventricular arrhythmias, and assists in evaluation of improved strategies for shock delivery. PMID- 8434818 TI - Computer-aided vascular experimentation: a new electromechanical test system. AB - We present a new computer-controlled, electromechanical system for performing simultaneous extension, inflation, and torsion experiments on cylindrical segments of natural and artificial blood vessels. Specimens are tested while immersed in a temperature-controlled, oxygenated, physiologic solution. Deformations are measured within a central region of the specimen using noncontacting video methods. The associated axial loads, luminal pressures, and torques are measured with standard transducers. Data are collected and stored on line, and are used in the feedback control of experimental protocols, which are prescribed using custom interactive software. Finally, we present illustrative data obtained from canine aortas and common carotid arteries. PMID- 8434819 TI - Simple calculation of the velocity profiles for pulsatile flow in a blood vessel using Mathematica. PMID- 8434820 TI - Development of a device for measuring adherence of skin grafts to the wound surface. AB - Adherence of a biological graft to the wound surface is the most important factor influencing the ultimate success of graft viability. A machine has been developed to test the adherence of biological graft materials to a substrate such as a wound surface. The peeling mode, which yields reproducible quantitative measurements of adherence, is a standard method for testing adhesives. The device is designed to continuously measure the force required to peel the graft from the substrate at a constant rate. This force is a function of the energy of adhesion per unit area of adhered surface. This device has been used to measure the peeling force of (2 x 2 cm) skin grafts which are applied to full-thickness wounds on mice. Results of tests on adherence of autografts on mice show that the peeling force increases significantly with time over the first 9 days of healing. Thus, this device is useful in quantitative comparison of various skin grafting techniques and artificial grafts. PMID- 8434821 TI - Bioreactor based on suspended particles of immobilized enzyme. AB - A bioreactor for blood detoxification was developed in which oscillation-induced secondary flows suspend particles of immobilized enzyme in a reactor operating at clinically useful flowrates. Torsional oscillation of the reactor about its axis created a pair of counterrotating toroidal vortices which were readily observed in flow-visualization studies. Oscillation frequencies were selected to provide spatially uniform particle dispersion, as assessed visually. As a model system, blood deheparinization by reactors containing heparinase immobilized to agarose particles was investigated. Identical deheparinization profiles were observed in the continuous-flow reactor and in independent batch studies, done in well mixed test tubes of blood, demonstrating that the oscillating reactor design minimizes external mass transfer limitations. Identical heparin neutralization profiles and rates were also observed in the first and the second of consecutive heparin neutralization studies (0-2 h and 2-4 h, respectively) demonstrating an effective half-life of the immobilized enzyme in the oscillating reactor of at least 4 h. No significant decrease in red or white blood cell count, platelet count, or hematocrit, and clinically acceptable levels of plasma hemoglobin and activated complement were observed with 2 h (20 passes) of in vitro recirculation of human blood through the reactor. High, stable efficacy, operational stability, and excellent biocompatibility are attributed to secondary flow induced liquid particle mixing within the oscillating reactor. PMID- 8434822 TI - Kinetics of immobilized heparinase in human blood. AB - Immobilized enzyme reactors can form the basis of useful blood detoxification systems. One such reactor was developed for heparin neutralization by immobilized heparinase. In this article, reactor kinetics were studied under clinically relevant conditions. Heparin neutralization was assessed in vitro in whole human blood using (a) a well-mixed batch reactor, and (b) an oscillating, continuous flow reactor. The kinetics of heparin neutralization in human blood were first order over the entire range of heparin and enzyme concentrations and particle fractions tested. The kinetic rate was not sensitive to physiological variations in the concentration of antithrombin, a heparin binding protein in blood. Enzyme activity did not decrease significantly over the 2 hour test period. Kinetic control of the system with minimal intraparticle diffusional limitations was suggested by the Thiele moduli (0.11-0.67) and effectiveness factors (0.98 +/- 0.01). The ratio kcat/Km obtained in batch studies was 0.0028 +/- 0.0008 cm3/microgram-min. A continuous-flow oscillating reactor within a closed recirculation loop performed as a single well mixed batch reactor; there was a short mixing time of recirculating blood when compared to reaction time. A model based on this mixing pattern and the kinetics obtained in independent batch studies accurately predicted heparin neutralization profiles observed in the continuous-flow system. PMID- 8434823 TI - Design and construction of a linear shear stress flow chamber. AB - A new parallel plate flow chamber that has a linear variation of shear stress, starting from a predetermined maximum value at the entrance and falling to zero at the exit, has been designed and tested. This is in contrast to the usual rectangular channel plan which produces a constant shear stress over the entire length. The new design is based on the theory of Hele-Shaw flow between parallel plates. To verify the efficacy of the flow channel, the effect of fluid shear stress on platelet adhesion to a fibrinogen-coated glass surface was tested. The percentage of attached platelets after 5 min of shear stress is shown to be a function of shear stress. With this new flow chamber, cell-cell interactions can be studied efficiently over a wide range of shear stress using a single run at constant discharge. PMID- 8434824 TI - Application of adaptive FTF/FAEST zero tracking filters to noninvasive characterization of the sound pattern caused by coronary artery stenosis before and after angioplasty. AB - This article presents a new signal processing application that can be used for acoustical detection of coronary artery disease before and after angioplasty. The adaptive Autoregressive (AR) method based on the FTF/FAEST (Fast transversal filters/Fast a posteriori error sequential techniques) is used to track acoustical behavior associated with coronary occlusions. Using the amplitude trajectory of the second pole pair of this method, 9 out of 10 angioplasty patients were correctly identified using a blind protocol without prior knowledge of whether a given recording was made before and after angioplasty. These results were obtained from signals located between 200 and 300 msec after the end of the second heart sound during the diastolic period. PMID- 8434825 TI - History of CPR and the role of the national conference. AB - External defibrillation was first reported in 1956, mouth-to-mouth ventilation was first reported in 1958, and closed-chest compression in 1960. While these developments began the modern era of CPR, accounts of resuscitative efforts go back to ancient times. The guidelines for CPR and emergency cardiac care (ECC) have evolved through five national conferences, held in 1966, 1973, 1979, 1985, and most recently in February 1992. The purpose of these conferences was to review and update published materials in the light of scientific advances and clinical experience. This issue of the Annals of Emergency Medicine contains the proceedings of the most recent National Conference on CPR and ECC. At this conference, a consensus was reached by an international gathering of scientists and clinicians for guidelines on adult basic and advanced life support, as well as on pediatric and neonatal life support. PMID- 8434826 TI - Mechanisms of blood flow during CPR. AB - Animal studies suggest that there are two mechanisms for blood flow during CPR: manipulation of intrathoracic pressure and/or direct cardiac-vascular compression. These mechanisms are not necessarily mutually exclusive and may coexist during different phases of prolonged resuscitation. Data in man, however, are inconclusive. Several studies suggest that intrathoracic pressure manipulation is a potent mechanism for blood flow during CPR in man. Other observations support the likelihood of cardiac-vascular compression. In addition, there is a lack of consensus on the best parameter(s) to use in studying the mechanism of flow. Despite these limitations, the better understanding of the physiology of CPR has led, in turn, to the development of more focused mechanical and pharmacological strategies to improve vital organ perfusion during resuscitation. PMID- 8434827 TI - Hemodynamic monitoring during CPR. AB - Real-time hemodynamic monitoring provides useful information that can be used to assess and optimize mechanical and pharmacological interventions during CPR. The standard algorithms should always be the initial approach to resuscitation, because they offer a rapid, logical, coordinated series of treatments with proven success. Pressure and flow measurements during conventional, closed-chest CPR in humans indicate that the technique typically produces a hemodynamic state resembling profound cardiogenic shock, with a low systemic arterial pressure, markedly reduced cardiac output, and high intravascular filling pressures. End tidal carbon dioxide monitoring provides useful, noninvasive information during clinical resuscitation. A low end-tidal carbon dioxide value during resuscitation should alert the rescuers that something is wrong with ventilation, perfusion, and/or carbon dioxide production and should prompt a search for correctable causes. If one or more hemodynamic parameters are being monitored at the time the patient develops cardiac arrest (eg, an intensive care unit patient who has an arterial line and a pulmonary artery catheter in place), it is appropriate for the resuscitation team to pay attention to the data that are generated during the resuscitation, particularly if the initial algorithm approach is not successful. For patients who are not being monitored at the time of their arrest, end-tidal carbon dioxide measurements provide noninvasive, semiquantitative information that can help the team detect and troubleshoot problems during resuscitation. Further research and better, more affordable technologies are needed to provide in- and out-of-hospital resuscitation teams feedback on the hemodynamic effectiveness of their resuscitative efforts. PMID- 8434828 TI - Electrical treatment of cardiac arrhythmias: defibrillation and cardioversion. AB - The passage of electrical current across the chest and heart to terminate ventricular fibrillation (defibrillation) or organized supraventricular or ventricular arrhythmias (cardioversion) is effective and safe. This paper reviews the physiology, techniques, and rationale for defibrillation and cardioversion. New developments and future directions are discussed. Rapid defibrillation is the most important factor in survival of out-of-hospital ventricular fibrillation. PMID- 8434829 TI - Maintenance of defibrillators in a state of readiness. AB - Since 1984, the US Food and Drug Administration (FDA) has utilized the Medical Device Reporting system as a mechanism for reporting adverse incidents associated with the use of medical devices, including external defibrillators. The frequency and content of these reports prompted an FDA-conducted five-state study of defibrillator-user training and maintenance practices for both devices and batteries. The study also included inspection and testing of defibrillators and batteries to assess their state of maintenance. A detailed review of the reports and of the five-state data confirmed that in the majority of cases, adverse incidents were related to improper defibrillator operation and maintenance, prompting the FDA Center for Devices and Radiological Health to launch an educational effort directed toward those who operate and maintain defibrillators. Proper maintenance of batteries (both nickel-cadmium and sealed lead-acid) was a major component of the educational thrust, because battery failure was identified as a recurrent and preventable problem. In an effort to correct the diverse types of incidents being reported, checklists were developed by the FDA for both manual and automated defibrillators. The checklists are designed to cover the spectrum of reported problems related to both device and user. The advent of more stringent FDA adverse incident-reporting regulations, coupled with increased use of defibrillators in diverse settings with varying usage frequencies, would seem to give a major impetus to the regular use of these checklists wherever defibrillators are employed. PMID- 8434830 TI - The use of antiarrhythmics in advanced cardiac life support. AB - Antiarrhythmic agents have been used to treat malignant ventricular arrhythmias in the setting of acute myocardial ischemia with proven efficacy for many years. Thus, it has been presumed that these agents would be efficacious for the treatment of cardiac arrest. Unfortunately, hard data supporting this contention are unavailable to date. Furthermore, some of the experimental data in this area are conflicting, especially regarding the relative effects of lidocaine and bretylium. Thus, little definitive can be said based on experimental information. In two randomized patient studies, lidocaine and bretylium performed comparably. Because of the frequent use of lidocaine and thus the familiarity of most health care professionals with its use, it makes educational sense to utilize lidocaine as the antiarrhythmic drug of first choice during the cardiac arrest sequence. Recent data suggesting that amiodarone may be efficacious in patients with recurrent arrhythmias require additional confirmation. Although antiarrhythmic agents have been shown to be effective in the treatment of malignant arrhythmias in patients with acute myocardial infarction, their use prophylactically for patients with suspected infarction (advocated in the past) has recently undergone reevaluation. It is now clear that despite a reduction in ventricular fibrillation, overall mortality may be increased. This may be because the prophylactic treatment of patients with suspected infarction includes a large number of patients not at risk for ventricular fibrillation who still may be at risk for drug toxicity. Thus, prophylactic administration of lidocaine to all patients with suspected acute myocardial infarction can no longer be recommended. There are inadequate data upon which to base a recommendation concerning the use of lidocaine in patients receiving thrombolytic therapy. The group most likely to benefit from lidocaine are patients with ST segment elevation who present early after the onset of acute myocardial infarction. The use of lidocaine in this group requires additional study. At present, despite enthusiasm for the prophylactic use of magnesium for the treatment of arrhythmias, data are inadequate to support its routine administration. However, given the importance of magnesium and potassium levels in the genesis of malignant arrhythmias, their levels in plasma should be assessed, and abnormalities should be promptly corrected. The potential uses of antiarrhythmic agents during advanced cardiac life support span a remarkably diverse number of applications. For the purpose of this review, only the use of these agents during CPR and during the early hours of acute or suspected acute myocardial infarction will be considered. PMID- 8434831 TI - Pharmacologic controversies in CPR. AB - Since the 1985 Emergency Cardiac Care Conference, numerous controversies about the pharmacology of CPR have arisen (eg, questions about the pharmacokinetics and pharmacodynamics of drugs during CPR, the optimal vehicle for delivery of medications, and the dose of atropine in brady-asystolic cardiac arrest). This article has three objectives: 1) to critically explore these controversies, 2) to provide recommendations for clinical practice, and 3) to identify areas for future study. The ideal route is one which combines rapid access with quick delivery of drug to the central circulation. Because of hemodynamic changes during CPR, administration of drugs into the central circulation is preferable when compared with peripheral venous injection. Whenever drugs are administered from a peripheral i.v. site, the extremity should be elevated, and a 20-mL bolus of i.v. fluid should be given to facilitate access of the agent to the central circulation. If there is a delay in obtaining venous access, epinephrine, lidocaine, and atropine may be administered through the endotracheal tube at 2.5 times the i.v. dose. When administering these drugs through the endotracheal tube, dilute the drug in 10 mL of saline or water and inject it through a long catheter beyond the tip of the endotracheal tube. Dextrose 5% water is the primary vehicle for drug delivery during CPR. However, the administration of glucose during CPR is controversial because of the potentially detrimental effects of hyperglycemia on neuronal function during periods of ischemia. Data are inconclusive regarding the effects of glucose levels on neurologic outcome following resuscitation. Hyperglycemia may be a marker for prolonged resuscitation with subsequent impairment in insulin release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8434833 TI - Psychological issues in CPR. AB - CPR has been incorporated into emergency cardiac care with the evolution of both basic and advanced life support components. To date, however, the psychological issues associated with these skills have not been addressed. These issues include the psychological impact of failed resuscitation on the rescuer, the importance of breaking bad news is an empathetic and grief facilitating way to family members and the importance of emergency workers attending to their own feelings and health (critical incident debriefing). This paper describes ongoing research on the impact of CPR on the rescuer, discusses a method of talking to families after a loved one has suddenly died, and provides insights into the psychological dysfunctions that emergency personnel may be exposed to. The technique and importance of critical incident debriefing following an unsuccessful CPR attempt is discussed. PMID- 8434832 TI - Cerebral resuscitation after cardiac arrest: research initiatives and future directions. AB - At present, fewer than 10% of cardiopulmonary resuscitation (CPR) attempts prehospital or in hospitals outside special care units result in survival without brain damage. Minimizing response times and optimizing CPR performance would improve results. A breakthrough, however, can be expected to occur only when cerebral resuscitation research has achieved consistent conscious survival after normothermic cardiac arrest (no flow) times of not only five minutes but up to ten minutes. Most cerebral neurons and cardiac myocytes tolerate normothermic ischemic anoxia of up to 20 minutes. Particularly vulnerable neurons die, in part, because of the complex secondary post-reflow derangements in vital organs (the postresuscitation syndrome) which can be mitigated. Brain-orientation of CPR led to the cardiopulmonary-cerebral resuscitation (CPCR) system of basic, advanced, and prolonged life support. In large animal models with cardiac arrest of 10 to 15 minutes, external CPR, life support of at least three days, and outcome evaluation, the numbers of conscious survivors (although not with normal brain histology) have been increased with more effective reperfusion by open chest CPR or emergency cardiopulmonary bypass, an early hypertensive bout, early post-arrest calcium entry blocker therapy, or mild cerebral hypothermia (34 C) immediately following cardiac arrest. More than ten drug treatments evaluated have not reproducibly mitigated brain damage in such animal models. Controlled clinical trials of novel CPCR treatments reveal feasibility and side effects but, in the absence of a breakthrough effect, may not discriminate between a treatment's ability to mitigate brain damage in selected cases and the absence of any treatment effect. More intensified, coordinated, multicenter cerebral resuscitation research is justified. PMID- 8434834 TI - Ensuring the effectiveness of community-wide emergency cardiac care. AB - To improve emergency cardiac care (ECC) on the national or international level, we must translate to the rest of our communities the successes found in cities with high survival rates. In recent years, important developments have evolved in our understanding of the treatment and evaluation of cardiac arrest. Some of the most important of these developments include 1) recognition of the chain of survival, which is necessary to achieve high survival rates; 2) widespread acceptance that survival rates must be assessed routinely to ensure continuous quality improvements in the emergency medical services (EMS) system; and 3) development of improved methods for performing survival rate studies that will maximize the effectiveness of information gathering and analysis. While each community should determine how to optimize their own ECC services, some general guidelines are useful. Successful treatment of cardiac arrest starts in the community with prevention and education, including early recognition of the signs and symptoms of cardiovascular ischemia. Obtaining 911 service (and preferably enhanced 911) should be a top priority for all communities. EMS dispatchers should dispatch the unit to the scene in less than one minute, provide critical information to the responders regarding the type of emergency, and offer the caller telephone-assisted CPR instructions. The EMS first-responders should strive to arrive at the patient's side in less than four minutes, be able to immediately defibrillate if necessary, and begin basic CPR. An excellent strategy to accomplish this is to equip and train all fire-fighting units in the operation of automatic external defibrillators and dispatch them as a first-responder team. To manage the cardiac arrest patient, a minimum of two rescuers trained in advanced cardiac life support plus two or more rescuers trained in basic life support are needed. Furthermore, an EMS system is not complete without on-going evaluation. Therefore, the 1992 National Conference on CPR and ECC strongly endorses the position that all ECC systems assess their survival rates through an ongoing quality improvement process and that all members of the chain of providers should be represented in the outcome assessment team. We still have much to discover regarding optimal techniques of CPR, methods for data collection, and optimal structure of an EMS system. Research in these areas will provide the foundation for future changes in EMS systems development. PMID- 8434835 TI - Drowning issues in resuscitation. AB - Submersion injury is so often lethal because it inflicts severe hypoxia. To prevent hypoxic end-organ damage to the heart and brain, the goals of resuscitation are immediate ventilation and oxygenation. Issue 1: Should submersion victims receive the Heimlich maneuver? The pathophysiologic assumptions for this intervention are that water in the airway is obstructive, thus precluding ventilation, and that aspiration of water is the major injury. Anecdotal case reports describe improved ventilation of some victims who failed prior ventilatory efforts. However, animal and human studies support that aspirated water is rapidly absorbed, does not preclude ventilation and intubation, and is best treated rapidly with positive pressure ventilation. With inadequate data to support benefit from the Heimlich maneuver and concern that the Heimlich maneuver would delay initiation of ventilation, basic life support procedures are recommended in managing the airway of the submersion victim. Issue 2: What is the role of prehospital care? Outcomes of submersion victims treated with rapid, aggressive prehospital care show that the window for medical intervention for the submersion victim is in the prehospital setting, not in the emergency department or intensive care unit. The submersion victim should be provided advanced cardiac life support, including intubation as needed, as soon as possible. PMID- 8434836 TI - Hypothermia. AB - Significant hypothermia is an increasing clinical problem that requires a rapid response with properly trained personnel and techniques. Although the clinical presentation may be such that the victim appears dead, aggressive management may allow successful resuscitation in many instances. Initial management should include CPR if the victim is not breathing or is pulseless. Further core heat loss should be prevented by removing wet garments, insulating the victim, and ventilating with warm humidified air/oxygen to help stabilize core temperature. Core temperature and cardiac rhythm should be monitored in the prehospital setting, if possible, and CPR should be continued during transport. In-hospital management should consist of rapid core rewarming in the severely hypothermic victim with heated humidified oxygen, centrally administered warm IV fluids (43 C), and peritoneal dialysis until extracorporeal rewarming can be accomplished. Postresuscitation complications should be monitored; they include pneumonia, pulmonary edema, cardiac arrhythmias, myoglobinuria, disseminated intravascular thrombosis, and seizures. The decision to terminate resuscitative efforts must be individualized by the physician in charge. PMID- 8434837 TI - Electrical shock and lightning strike. AB - Cardiac arrest from electrical shock or lightning strike is associated with significant mortality and requires modification and extension of standard advanced life support measures to achieve successful resuscitation. Patients who experience electrical shock or lightning strike may sustain cardiac and respiratory arrest secondary to the direct effects of current. However, the majority of victims have associated multisystem involvement, including neurologic complications, cutaneous burns, and associated blunt trauma. As a result, a combination of advanced cardiac life support measures and advanced trauma life support techniques is indicated. Victims with cardiac arrest from electrical shock or lightning strike require prompt, aggressive resuscitation using standard methods for airway control, ventilation, and chest compressions, as well as usual measures for defibrillation and cardiac pharmacotherapy. Unique considerations include vigorous fluid resuscitation and spinal immobilization for victims of electrical shock and reversal of normal multiple casualty triage priorities when managing several lightning strike victims. Because the majority of victims are relatively young and seldom have significant underlying cardiac disease, the chance for successful resuscitation may be greater for patients who experience sudden death from electrical shock or lightning strike than for those with other causes of cardiac arrest, even among patients with initial rhythms traditionally unresponsive to therapy. Although numerous specialized aspects are required for the successful management of victims of electrical shock and lightning strike, the following article focuses on the unique considerations necessary for immediate care of cardiac arrest victims, with emphasis on the underlying mechanisms of sudden death and currently recommended guidelines for resuscitation. PMID- 8434838 TI - CPR challenges in pediatrics. AB - The concept of the chain of survival for children has been extended to include prevention, bystander CPR, prehospital CPR, and acute care. Two clinical cases are presented as examples. The current status and possible weaknesses in each link of the chain are discussed, and suggestions are made for possible research initiatives. PMID- 8434839 TI - Invasive airway techniques in resuscitation. AB - Although endotracheal intubation is still the most definitive technique for airway management in patients with cardiac or respiratory arrest, in some emergency care systems, use of endotracheal intubation by prehospital care personnel has been restricted by policy or statute. Therefore, alternative airway devices have been developed. These alternative airway devices include the Esophageal Obturator Airway (EOA) and Esophageal Gastric Tube Airway (EGTA), the Pharyngeotracheal Lumen Airway (PTL), and the Esophageal-Tracheal Combitube (ETC). By examining the available literature concerning these alternative airway devices, we sought to determine 1) if these devices are superior to basic, noninvasive airway techniques (eg, bag-valve-mask ventilation); 2) if they are comparable to endotracheal intubation in terms of ventilation, oxygenation, and potential complications; 3) what the role of these devices should be in prehospital care; and 4) what the best recommendations should be regarding these devices in terms of resuscitation training and future areas for research. The review involved a total of 837 EOA/EGTA, 304 PTL, and 159 ETC study patients. Although ventilation and oxygenation can, in some circumstances, be as good with the EOA/EGTA devices as it is with the endotracheal intubation, in some cases they can be inadequate, and the complication rate is relatively high. Preliminarily, the PTL and the ETC seem to provide adequate ventilation and oxygenation with few complications. However, for both devices, published clinical experience, especially in the prehospital setting, is still limited. Therefore, their use should be left to the discretion of accountable physician directors of applicable resuscitation teams. Regardless of the device used, recognition of proper placement remains the most important aspect of using any invasive airway device. Therefore, proper training and expert medical supervision probably have more influence on the successful use and impact of these devices than any other factors related to the devices themselves. Future training efforts would be most useful if directed at proper endotracheal intubation training and development of improved basic ventilatory skills. Nevertheless, additional controlled, direct comparison studies of the PTL and ETC devices are recommended and should be conducted in properly supervised emergency medical services systems. PMID- 8434840 TI - Pathophysiologic and therapeutic implications of acid-base changes during CPR. AB - Acid-base changes occurring during cardiac arrest and subsequent CPR are related to a complex low-perfusion state characterized clinically by venous and tissue hypercarbic and metabolic (lactic) acidosis. This low-flow state is a dynamic process dependent on the time intervals between onset of arrest, initiation of CPR, and restoration of adequate spontaneous circulation. Increased release of CO2 from ischemic tissues and reduced CO2 transport from the tissues to the lungs result in profound tissue acidosis. However, recent experimental data suggest that even very low pH is compatible with neurologically intact survival. Thus, the clinical use of buffer agents, and especially of sodium bicarbonate, is currently controversial. Because results of controlled clinical studies are not available, a careful review of well-performed experimental studies is necessary. So far, the use of either CO2-generating or CO2-consuming buffers has not been proved conclusively to increase neurologically intact long-term survival after CPR. More importantly, adequate ventilation and effective chest compressions must be quickly established after cardiac arrest. This will counterbalance the hypercarbic and metabolic acidemia of cardiac arrest by creating concurrent hypocarbic arterial alkalemia during at least the early phase of CPR. Thus, the treatment of the complex acid-base changes associated with CPR is based primarily on the classical maneuvers of A and B (airway and breathing = adequate oxygenation and ventilation), C (chest compressions), and D (early defibrillation for rapid restoration of spontaneous circulation). In cases of prolonged cardiac arrest or preexisting metabolic acidemia, buffer therapy may be indicated. PMID- 8434841 TI - Thrombolytic therapy. AB - All patients with symptoms and ECG findings suggestive of acute myocardial infarction (AMI) should be considered for treatment with thrombolytic agents. The decision to use thrombolytic therapy is a clinical judgment based upon a weighing of the potential benefits versus the possible risks. The physician must take into account relative contraindications, age of the patient, area of jeopardized myocardium, and duration of symptoms. Health professionals involved in the care of AMI patients should develop written plans and protocols addressing the following matters: identification of patients with chest pain in the prehospital setting (this applies to hospitals that receive patients from emergency medical services systems), triage of patients in the emergency department, obtaining the 12-lead electrocardiogram, determination of contraindications, authority for ordering thrombolytic therapy, and consultation for atypical cases. There also should be agreed standards for the time interval from arrival in the ED to administration of the thrombolytic agent, as well as a commitment to the prospective monitoring of procedures and times to assure continuous improvement. A time interval for treatment (arrival in ED to administration of drug) of 30 to 60 minutes should be achievable for patients who present with typical symptoms and ECG findings. PMID- 8434842 TI - Citizen response to cardiopulmonary emergencies. AB - Since 1985, it has become apparent that the key to survival from adult sudden cardiac death is prompt defibrillation. Any delay from the time of collapse to the initial countershock will decrease the likelihood of survival. It also has been determined that CPR performed by lay rescuers is not begun promptly and, once started, often is performed for more than one minute before the emergency medical services (EMS) system is accessed, which significantly delays the time to defibrillation. In adults, therefore, the rescuer should phone first to activate the EMS system before performing CPR. In the pediatric population, respiratory arrests are far more common than cardiac arrests. Therefore, a rescuer should perform one minute of rescue support before activating the EMS system (a concept termed phone fast). It is recognized that this change is dependent upon a national EMS system that is still evolving. It is hoped that this change to phone first and phone fast will provide an impetus for rapid development of the EMS infrastructure. PMID- 8434843 TI - Medications in neonatal resuscitation. AB - Medication usage in neonatal resuscitation has been largely extrapolated from adult resuscitation guidelines. Compared to older children and adults, newborn infants have major anatomical and physiological differences which affect their need for and response to medications during resuscitation. This article discusses some of these differences, highlights the discussion of the Emergency Cardiac Care Panel for Neonatal Pharmacology, lists the recommendations of the panel to the Emergency Cardiac Care Committee, and discusses areas of future research in neonatal resuscitation. PMID- 8434844 TI - Pediatric airway control and ventilation. AB - Emphasis on a clear airway is a primary requisite for effective CPR. Airway control in the trauma victim needs special consideration of the possibility of associated cervical vertebrae and spinal cord injury; thus, modification of the patient positioning for transport is essential. Emphasis on visualization of chest movement is the most important factor in assessing adequacy of ventilation. Experience in the use of bag-valve-mask devices requires appropriate instruction and on-going practice. Small bag volume devices limit the ability to provide adequate tidal volumes and prolong inspiratory times. Tracheal intubation provides optimal airway management. In-field use of this procedure will depend upon the skill and experience of the operator. Validation of correctness of tracheal tube placement is critical; seeing the tube pass the glottic opening on laryngoscopy, bilateral and equal chest movement, auscultation of breath sounds in the chest. Methods to measure end-tidal CO2 as a valuable check for tube position is a useful adjunct but must not be relied upon. Foreign body management continues to be controversial and remains unchanged for the present; ie, the infant < 1 year of age the recommendations are back blows followed by chest thrusts. Above 1 year of age, abdominal thrusts (Heimlich maneuver) is recommended. PMID- 8434845 TI - Pediatric resuscitation pharmacology. Members of the Medications in Pediatric Resuscitation Panel. AB - The goal of resuscitation pharmacology is to restart the heart as quickly as possible while preserving vital organ function during chest compression. Unfortunately, the application of advanced life support to pediatric cardiac arrest patients is often unsuccessful. The goal of this paper is to review the scientific rationale and educational considerations used to derive the guidelines for medication use in the pediatric patient during CPR. The first step in drug delivery during CPR is to achieve vascular access. The endotracheal route and intraosseous route may be used, although the former is not reliable. To maximize endotracheal drug effect, a larger dose should be instilled into the airway as deeply as possible. Any vascular access, including intraosseous, is preferable to endotracheal drug administration. Although other alpha-adrenergic agents are theoretically superior, epinephrine remains the drug of choice in pediatric resuscitation. The previously recommended dose, however, may be inadequate; a dose 10 to 20 times larger (100-200 micrograms/kg) should be considered, particularly if the standard dose is ineffective. Lacking convincing data, the indications and dose for calcium are unchanged. Similarly, there are no data advocating a change in the indications or dose for lidocaine, bretylium, or atropine. The treatment of arrest-induced acidosis remains controversial. The mainstay of therapy consists of efforts to maximize oxygenation and tissue perfusion. Bicarbonate is not a first-line drug; its use should be considered when the patient fails to respond to advanced life support efforts, including the administration of high-dose epinephrine. Bicarbonate may be helpful in the postresuscitation setting, but its use should not supplant efforts to maximize tissue perfusion. Adenosine is an effective and generally safe medication for the treatment of supraventricular tachycardia in infants and children. Therefore, its indications, dose, and toxicities should be included in the new guidelines. Finally, a summary of research initiatives are included, including a call for the development of a multi-institutional pediatric clinical resuscitation research group. Large numbers of patients must be enrolled in a standardized manner to better evaluate the benefits and adverse effects of various therapies. This includes the use of high-dose epinephrine, calcium, bicarbonate, and other buffer agents such as Carbicarb and THAM. Animal models simulating the etiology and pathophysiology of pediatric arrest also are needed. In both clinical and animal studies, neurologic outcome and long-term survival should be assessed rather than simply the rate of restoration of spontaneous circulation. PMID- 8434846 TI - Pediatric injury prevention. AB - Pediatric injuries are the leading cause of childhood death and disability and are responsible for more childhood deaths than all other diseases combined. The panel summarized the principles of pediatric injury prevention and reviewed the incidence, epidemiology, and prevention of six common pediatric injuries. PMID- 8434847 TI - Education in adult basic life support training programs. AB - The Panel on Educational Issues in Adult Basic Life Support Training Programs reviewed the characteristics of adult learners, aspects of educational theory, issues concerning barriers to learning and performing CPR, and issues concerning testing and evaluation. The panel made the following recommendations: a comprehensive evaluation of the basic life support program with the goal of improving the program design and educational tools must be initiated; adult programs must be designed to motivate laypersons to become trained in CPR, as well as to target relatives and friends of high-risk individuals; and emotional and attitudinal issues, including the student's reluctance to act in an emergency, must be addressed. Programs must incorporate information on the willingness of an individual to perform CPR; CPR programs must be simplified and focus on critical success factors; flexible educational approaches in programs are encouraged; flexible programming that addresses the needs of the allied health professional is encouraged; formal testing should be eliminated for layperson programs; and formal testing for health care providers and instructors should be continued. PMID- 8434849 TI - The educational direction of the ACLS training program. PMID- 8434848 TI - Education in adult advanced cardiac life support training programs: changing the paradigm. Members of the Advanced Cardiac Life Support Education Panel. AB - To develop a consensus for change in the educational aspects of the Advanced Cardiac Life Support (ACLS) Training Program, the American Heart Association appointed panel members to engage in a consensus process. At a preconference meeting held in the fall of 1991, panel members received broad input from experts in adult education, experienced ACLS educators, and resuscitation scientists. The panel then developed a statement based on the preconference discussions and presented it at the National Conference on CPR and Emergency Cardiac Care held in February 1992. The conference's recommendations and the process that led to them are described in this paper. The key conclusions of the consensus process are as follows. The purpose of ACLS programs is the education of health professionals whose jobs include the management of patients in arrest or near-arrest. The goal of each ACLS course is to have each participant succeed in acquiring the skills and knowledge required for resuscitation. Aspects of the course which threaten failure or raise anxiety should be minimized or eliminated. ACLS course directors are strongly encouraged to design courses whose content and presentation are best suited to the training, experience, and needs of the course participants. Flexibility is strongly encouraged. Evaluation (testing) should be used primarily for its educational value, to help both learners and instructors identify areas needing improvement. The problem learner should be identified as early as possible and should receive intensive remediation to achieve the goal of every participant acquiring the targeted skills and knowledge. Because skill retention is variable, rescuers should practice skills frequently in regular refresher sessions. At a minimum, retraining every two years is strongly recommended. PMID- 8434850 TI - Education in pediatric basic and advanced life support. AB - Curricula in pediatric resuscitation must be based on adult learning principles. The Pediatric Basic and Advanced Life Support Courses (PBLS, PALS) should use educational strategies fostering positive interactions between the instructor and learners and should take into consideration the learner's motivation for taking the course. Materials should be developed for a specific target audience; course design should be flexible to meet individual needs. The PBLS and PALS courses have different audiences. PBLS is targeted toward caretakers of children. This course will continue to emphasize primary injury prevention as the major strategy but also will give learners the knowledge and skills to perform CPR. To optimize retention of knowledge and skills, the course content must be simplified, and the sequencing of steps in basic life support must be modified. Health care providers caring for pediatric patients in acute care settings are the primary audience for the PALS course. This course already incorporates adult learning principles; only minor revisions are anticipated. Discussion of the trauma patient is limited in the PALS course; additional trauma education could be facilitated by the addition of a trauma module or by other educational courses. All aspects of the PBLS and PALS educational programs must be evaluated continually to determine whether learning objectives have been met and whether the teaching format is appropriate. The answers to evaluation questions will help determine the degree to which the American Heart Association is meeting its educational objectives and how to allocate resources for development and training. PMID- 8434851 TI - Ethical issues in adult resuscitation. AB - The ethics panel of the American Heart Association recommended that ethical values, including patient autonomy and provider advocacy, should guide the provision of advanced cardiac life support (ACLS) and emergency cardiac care (ECC). The panel developed guidelines regarding the institution and withdrawal of basic life support, ACLS, and the criteria for the determination of death. A discussion of futility, No-CPR orders, living wills, advance directives, and their impact on ECC is included. PMID- 8434852 TI - Ethical issues in pediatric and neonatal resuscitation. AB - CPR in infants and children has a number of unique clinical, legal, and ethical aspects. The distinguishing clinical aspects relate to the circumstances of pediatric cardiopulmonary arrest and their prognostic implications. The relevant legal and ethical considerations derive from the special triadic physician-child parent relationship, the standing of parents as surrogate decision makers, and the progressive development of decisional capacity in maturing children. This paper discusses the implications of guidelines and policies concerning decisions to provide, withhold, or withdraw CPR and life support systems. PMID- 8434853 TI - International emergency cardiac care: support, science, and universal guidelines. AB - Mature resuscitation councils must continue to support educational and training efforts of less-developed countries, but only when strong local interest exists. The scientific basis for the interventions and organization of emergency cardiac care is international in origin. Educational approaches are varied and innovative and should be shared. The era of single national guideline conferences on CPR and emergency cardiac care has ended. Future guideline conferences must cast a broad net to be more international in both participants and scientific knowledge. Existing organizations should support an international infrastructure to help pool scientific and educational expertise. PMID- 8434854 TI - Profiting from inventions in academia: American and British perspectives. PMID- 8434855 TI - Urine albumin should replace total protein for the assessment of glomerular proteinuria. PMID- 8434856 TI - Screening for microalbuminuria in a mixed ethnic diabetic clinic. PMID- 8434857 TI - Raised serum fructosamine concentration caused by IgA paraproteinaemia. PMID- 8434859 TI - Parathyroid hormone measurement. PMID- 8434858 TI - Delay in separation of blood samples. PMID- 8434860 TI - Troponin T for the differential diagnosis of ischaemic myocardial damage. AB - The diagnostic performance of a new enzyme linked immunosorbent assay for the cardiac structural protein troponin T in the differential diagnosis of ischaemic cardiac damage was assessed. A well documented set of patients admitted to the coronary care unit of a district general hospital were studied. At a cutoff value of 0.2 micrograms/L, troponin T measurements 12-24 h after admission or 12-16 to 24-48 h from onset of chest pain showed an overall efficiency of 97.6% for diagnosis of proven myocardial infarction. Troponin T was not detectable in patients when ischaemic heart disease could be excluded but was present in four patients with angina. Detectable troponin T in these angina patients was associated with subsequent cardiac events. PMID- 8434861 TI - Diagnosis of familial benign hypercalcaemia. PMID- 8434862 TI - Rapid enzyme diagnosis of patients with acute chest pain reduces patient stay in the coronary care unit. AB - We have studied the effect of early exclusion of myocardial infarction using rapid biochemical diagnosis on the management of patients admitted to the coronary care unit of a district general hospital. Diagnosis was based on the rate of creatine kinase increase in serial samples obtained over the 8 h following admission. For an initial 3-month familiarization period serial creatinine kinase results were made available at the end of working day to supplement clinical management, supported by our traditional protocol of admission and daily enzyme determinations. Subsequently, for a 4-month period, the admission to 8 h serial values were provided by 1100 h each day and usually within 24 h of admission. There was a net reduction in length of stay on the coronary care unit to a median 2 days (n = 66) compared with 3 days (n = 41) for patients without further cardiac symptoms or electrocardiographic changes suggestive of ischaemia or infarction. This change was significant, P = 0.007, Mann-Whitney U test. Reversion to the original protocol of daily enzyme estimations resulted in an increase in the length of stay on the coronary care unit back to a median of 3 days for this patient group. Rapid diagnostic protocols, applied within routine clinical practice, have the potential for real reduction in coronary care unit stay. PMID- 8434863 TI - Mononuclear blood cell magnesium in older subjects: evaluation of its use in clinical practice. AB - Serum and mononuclear blood cell (MBC) magnesium were measured in 24 healthy community subjects, average age 76 years (67-93), and in 21 ill hospitalized subjects, average age 79 years (65-90). MBC magnesium, expressed as mumol/mg protein, was significantly lower in the in-patient group (P < 0.001), but tended to be higher in the same group when expressed as fmol/cell (not significant). Further samples from community subjects on the same day, and again at 7 days, revealed coefficients of variation for intrasubject analysis of 12% and 22%, respectively (fmol/cell). The equivalent intrasubject values for serum were 2.8% on the same day and 4% at 1 week. MBC magnesium values for inpatients were probably distorted by changes in cell size and cell protein content caused by illness. Biological variability and the effects of illness on the composition and size of cells seem to limit the usefulness of MBC magnesium measurement as a clinical tool for assessment of body magnesium status. PMID- 8434864 TI - Detection of colorectal cancer by faecal alpha 1-antitrypsin. AB - Alpha 1-antitrypsin was measured in 5-day faecal collections from patients with colorectal cancer or adenomatous polyps and a symptomatic control group. Collections were homogenized and lyophilized prior to measurement of alpha 1 antitrypsin by radial immuno-diffusion. Colorectal cancer dry weight concentrations were significantly higher than the symptomatic control results, with 57% having results greater than 95% normal values of this control group. There was no significant difference between adenomatous polyp dry weight concentrations and symptomatic control results. Wet weight concentrations were calculated from wet/dry ratios. Colorectal cancer wet weight concentrations were significantly higher than symptomatic control results with 48% having results greater than 95% normal values of this control group. Alpha 1-antitrypsin was also measured in non-lyophilized samples from an asymptomatic control group (n = 39). Colorectal cancer wet weight concentrations were significantly higher than asymptomatic control results, with 62% having results greater than 95% normal values of this control group. Faecal alpha 1-antitrypsin measurement deserves further assessment for use in detecting colorectal cancer. PMID- 8434865 TI - Protein excretion after prolonged exercise. AB - Random urine samples were obtained from 16 healthy subjects (nine men and seven women) before and after a 100 Km hill walk for the estimation of total protein, albumin, N-acetyl-beta-glucosaminidase (NAG), retinol binding protein (RBP) and creatinine. The excretion of total protein, albumin and NAG (expressed in relation to creatinine excretion) increased significantly after the walk. The relative clearance of protein and albumin also increased. In four subjects serial measurements were made for 4 days and the excretion of albumin and NAG on the fourth day were similar to the pre-walk values. We conclude that proteinuria of prolonged exercise is at least partly due to reduced tubular reabsorption. PMID- 8434866 TI - Plasma and 24 h-urinary catecholamine concentrations in normal and patient populations. AB - Using a single HPLC-ECD methodology, plasma catecholamine data were compiled from 545 patients and 144 healthy subjects, and 24 h urinary free catecholamine data from 106 patients. From these data, normal reference ranges were derived for the clinical investigation of suspected phaeochromocytomas, specifically to address the question as to when a result is normal and when further investigation may be required. We have shown that noradrenaline and adrenaline concentrations in plasma and urine are not normally distributed, and basal plasma noradrenaline is significantly lower in normal volunteers than in hospital patients. We have also demonstrated that a reference range which does not take account of these factors will give a significant number of false-positive results. Age and sex did not appear to be significant variables for either plasma or urinary catecholamines. In the investigation of phaeochromocytoma, 95% confidence limits may be used as a warning to repeat sampling and 99% confidence limits as rendering the diagnosis extremely probable. In patients with phaeochromocytomas, urinary catecholamines had a 99.5% specificity and 100% sensitivity in the diagnosis, and thus provide for a rapid and efficient diagnostic screen. PMID- 8434867 TI - The role of expert systems in improving the test requesting patterns of clinicians. AB - The many strategies proposed for influencing the test requesting patterns of clinicians have had only limited success, largely because they are labour intensive and depend on motivation and commitment. Clinical protocols which have been locally agreed between laboratory staff and clinicians are potentially one of the more successful strategies, but detailed study of their application in different clinical settings has been limited by practical problems. Expert systems offer a way of implementing locally agreed protocols and, consequently, of assisting the identification, audit and refinement of laboratory testing strategies. Where these systems have been applied in specialist units they have resulted in savings in time by both clinical and laboratory staff, and an overall reduction in the number of clinical chemistry tests done within and out of hours. These systems offer promise as a method of improving laboratory utilization. PMID- 8434868 TI - Immunoaffinity purification of prostaglandin E2 and leukotriene C4 prior to radioimmunoassay: application to human synovial fluid. AB - When human synovial fluid as such was subjected to radioimmunoassays of prostaglandin E2 (PGE2) and leukotriene C4 (LTC4), there was no linear increase in PGE2 and LTC4 as the amount of synovial fluid was raised. For removal of substances thus disturbing the assay we developed a method of immunoaffinity purification of PGE2 and LTC4. A monoclonal antibody against PGE2 or LTC4 was coupled to BrCN-activated Sepharose 4B. When synovial fluid mixed with radiolabelled PGE2 or LTC4 was applied to the column of immobilized antibody, the ligand was adsorbed to the column and eluted with a mixture of methanol/water in a recovery of about 80%. The purified material showed a linearity between the amount of the sample and the value of radioimmunoassay. The one-step method was applied to synovial fluid from patients with rheumatoid arthritis, osteoarthritis and other joint diseases. PMID- 8434869 TI - A time-resolved fluoroimmunoassay for recombinant human interleukin-3. AB - We describe a time-resolved fluoroimmunoassay (TRFIA) for recombinant human interleukin-3 (IL-3). The assay design uses two different monoclonal anti-IL-3 antibodies, giving a two-site immunometric assay. The TRFIA for IL-3 is a direct adaptation from our existing ELISA for IL-3. By using the same assay configuration and exchanging a europium-streptavidin conjugate for alkaline phosphatase-streptavidin, we were able to minimize the time required to develop a TRFIA, but still increase the working range of the TRFIA over the ELISA by 20 fold. The limit of detection is 5 ng/L, with the limits of quantification set at 5 and 30,000 ng/L human plasma. PMID- 8434870 TI - A rapid method for measuring serum amyloid A protein by latex agglutination nephelometric immunoassay. AB - Serum amyloid A protein (SAA) is a sensitive acute phase reactant. We developed a method for the rapid measurement of human SAA in serum by kinetic nephelometry of anti-SAA antibody-coated latex agglutination. Measurement takes less than 6 min using an automated analyser. Standardization of the assay employs SAA-enriched high density lipoprotein as the primary standard. The values determined by our new method and by conventional enzyme-immunoassay showed good agreement (r = 0.988). The normal range was 0.17-10.0 mg/L [mean(SD)]. This rapid method should prove useful in clinical laboratories. PMID- 8434871 TI - Urinary retinol binding protein: stability and pre-analytical handling of specimens for its measurement. AB - The stability of retinol binding protein (RBP) in urine has been reassessed and was found to be pH-dependent, diminishing as urinary pH decreased. When urines were incubated at 4 degrees C for 1 week, statistically significant losses of RBP were observed at pH values less than seven, varying in degree in different urines. At 37 degrees C some urine specimens showed minor losses when incubated for periods up to 4 h. This was more marked at pH 5 than pH 7 with maximum losses of 26% and 12%, respectively. When adjusted to pH 7, urines showed no significant loss of RBP when stored at 4 degrees C for up to 2 weeks; at -20 degrees C no significant change in RBP concentration was found for at least 14 weeks. To minimize losses of RBP it is recommended that urine pH is adjusted to above seven immediately after voiding. PMID- 8434872 TI - The presence of antibodies against extractable nuclear antigens in serum: a comparison of immunoblotting versus radial immunodiffusion. AB - A commercial immunoblotting kit has recently been introduced to determine auto antibodies against extractable nuclear antigens. We compared this new test with radial immunodiffusion for its usefulness in the routine laboratory procedures of a general hospital. Antigen preparation in immunoblotting includes a protein denaturation step prior to electrophoretic separation of the different proteins. In this way antigenic determinants that depend heavily on the protein superstructure are lost. In theory, auto-antibodies against these epitopes may be missed. In our series of 100 samples that had tested positively for antinuclear antibodies, radial immunodiffusion was able to detect one SSA positive sample that was negative by immunoblotting. However, 47 samples positive in immunoblotting, 37 positive for UBP, seven for anti-SSA, are for anti-Jo-1, one for anti-RNP and one for anti-Sm were missed by radial immunodiffusion. Most of these samples had low antinuclear antibody titres (1/80 or 1/160). PMID- 8434873 TI - The effect of the concentration ratio of avidin and biotin on a single step sandwich enzyme immunoassay. AB - The interaction between biotin and avidin, used in a single-step enzyme immunoassay for ferritin determination, has been studied. The antigen is simultaneously bound by an antibody coated to a polystyrene bead and by an antibody coupled to biotin which reacts with avidin conjugated to peroxidase. We have assessed the optimal ratio between avidin, conjugated to peroxidase, and biotin, coupled to antibodies, to give rise to the best signal for a quantitative enzyme-immunoassay. We have found that a careful balance between biotinylated antibody and conjugated avidin is necessary for our purpose and a biotinylated antibody excess should be avoided since it causes a signal decrease. This ratio is uninfluenced by both the presence and the absence of the antigen. Thus, an avidin-biotin single-step methodology, which has proved to be reliable for routine use, was developed. PMID- 8434874 TI - An assessment of the effect of haematocrit on the HemoCue blood glucose analyser. AB - The HemoCue blood glucose analyser was investigated with particular respect to its susceptibility to influence by the haematocrit of the blood specimen. The red cells and plasma of fresh blood samples were separated and then recombined in proportions to give a range of haematocrit values and the resulting specimens assayed for glucose. The HemoCue exhibited no appreciable influence of haematocrit. The instrument was easy to use, stable and had good precision (CV 1.8%). However, results tended to be a little higher than those produced by a conventional laboratory analyser on whole blood and it is understood that the factory calibration of newer HemoCue instruments has been modified to correct for this. PMID- 8434875 TI - Multiple sclerosis: remyelination of nascent lesions. AB - The relationship between plaque pathology and disease duration was examined in 15 patients with multiple sclerosis who died early in the course of their illness. Myelin-stained sections revealed that most plaques examined in patients who died during the first month of their illness showed evidence of ongoing myelin destruction accompanied by a loss of oligodendrocytes. Plaques containing large numbers of oligodendrocytes were not observed in these patients, but were relatively common in patients who died more than 1 month after clinical onset. Remyelination affecting more than 10% of the plaque area was observed in 3 of 82 plaques in 5 patients who died within 10 weeks of clinical onset, in 38 of 105 plaques in 5 patients who died 3 to 10 months after clinical onset, and in 19 of 92 plaques in 5 patients who died 18 months or longer after clinical onset. The study provides new evidence that both oligodendrocytes and myelin are destroyed in new lesions, that this activity ceases completely in many lesions within a few weeks, and that remyelination frequently ensues following repopulation of the plaque by oligodendrocytes. The findings suggest that new lesions normally remyelinate unless interrupted by recurrent activity and that remyelinated shadow plaques are the outcome of a single previous episode of focal demyelination. PMID- 8434876 TI - Pathological findings at the site of conduction block in multifocal motor neuropathy. AB - We report on 2 patients with multifocal motor neuropathy with focal conduction block involving motor but not sensory fibers at the site of nerve swelling. A nerve biopsy specimen from adjacent to the enlargement in 1 patient showed a perivascular area containing scattered demyelinated axons surrounded by small onion bulbs. The observed pathological findings are consistent with the conduction block considered characteristic of this neuropathy, although the underlying immunological mechanisms for selectivity and persistence remain undetermined. PMID- 8434877 TI - Magnetic resonance imaging measurements and clinical changes accompanying transtentorial and foramen magnum brain herniation. AB - Current concepts of brain herniation have depended largely on correlating clinical signs and symptoms with indirect radiographic studies and the results of postmortem neuropathology. This article describes measurements on midsagittal magnetic resonance imaging (MRI) scans that distinctly define normal and abnormal rostral-caudal relationships between the diencephalic-mesencephalic junction and the plane of the tentorial incisura, herein termed the incisural line. We similarly provide quantitative MRI scan measurements relating the cerebellum and the plane of the foramen magnum, termed the foramen magnum line. Measurements from 156 midsagittal and 63 coronal MRI scans performed on 123 normal adults, placed the iter of the aqueduct 0.2 +/- 0.8 mm (mean +/- SD) below the incisural line and the cerebellar tonsils 0.1 +/- 2.1 mm below the foramen magnum line. Defining 2 SD from these norms as abnormal, 23 patients with intracranial mass or obstructive lesions showed 4 distinct patterns of brain herniation, i.e., upward or downward transtentorial shift with or without accompanying cerebellar tonsillar herniation. Five patients with posterior fossa masses demonstrated displacement of the iter above the incisura ranging from 1.6 to 6.3 mm. Eighteen patients with supratentorial masses demonstrated displacement of the iter ranging from 2.0 to 11.0 mm below the incisura. Two-thirds of patients with upward and one-half of those with downward transtentorial shift had concurrent tonsillar herniation. In acute illnesses, MRI scan changes anticipated or confirmed clinical signs of brain herniation. In chronic cases, clinical and MRI scans correlated less well, with MRI sometimes revealing major degrees of anatomical herniation well in advance of clinical abnormalities. PMID- 8434878 TI - Plasma and cerebrospinal fluid neurochemical pattern in Menkes disease. AB - Menkes disease is a neurodegenerative disorder of copper metabolism. Because the enzyme dopamine-beta-hydroxylase requires copper to catalyze the conversion of dopamine to norepinephrine, we reasoned that patients with Menkes disease would have a neurochemical pattern similar to that seen in patients with congenital absence of dopamine-beta-hydroxylase, i.e., high levels of dopamine, the dopamine metabolite dihydroxyphenylacetic acid (DOPAC), and the catecholamine precursor dihydroxyphenylalanine (DOPA), and low levels of norepinephrine and its neuronal metabolite dihydroxyphenylglycol (DHPG). We measured plasma and cerebrospinal fluid (CSF) levels of catechols in 10 patients ranging in age from 9 days to 27 months. In contrast to patients with congenital absence of dopamine-beta hydroxylase, norepinephrine levels were normal in plasma of 4 Menkes patients and in CSF of all 10 patients. However, the ratios of DOPA:DHPG and DOPAC:DHPG in plasma and CSF of Menkes patients were invariably increased beyond the ranges of control values. These neurochemical findings indicate partial deficiency of dopamine-beta-hydroxylase in Menkes patients, with compensatory increases in catecholamine biosynthesis in sympathetic nerves and in the brain. Increased tyrosine hydroxylation and increased exocytotic release of norepinephrine may be responsible for preservation of plasma and CSF norepinephrine levels in Menkes patients. The abnormal neurochemical pattern, including high ratios of DOPA:DHPG and DOPAC:DHPG, may serve as a biochemical marker for Menkes disease and provide a baseline against which the influence of proposed therapies can be judged. PMID- 8434879 TI - The influence of muscular lengthening on cramps. AB - Muscle cramps induced by voluntary contraction and by electrical stimulation of the peripheral nerve were studied electrophysiologically in 10 healthy subjects. The aim was to verify that cramps can be evoked by electrical stimulation of peripheral nerve and to clarify the physiological mechanism responsible by analyzing the effect of muscular stretching on cramps. Our results showed: (1) Cramps can be induced even after peripheral nerve block by electrical stimulation distal to the block. (2) No cramps were recorded during or following maximal voluntary contraction without muscular shortening, while 7 of 10 subjects showed a true cramp following maximal effort with shortening of the muscle. (3) Muscle stretching caused a sudden interruption of cramps induced by either voluntary contraction or electrical stimulation of the peripheral nerve, even after the induction of nerve block. (4) The lengthening state of the muscle can strongly influence the possibility of evoking cramps by electrical stimulation of nerve. Our study verifies the experimental model proposed by Lambert in 1969, emphasizing the relevance of frequency of stimulation and confirming the hypothesis that cramps are of peripheral origin. The effects of muscle stretch and lengthening on cramp interruption and development also have a peripheral mechanism. PMID- 8434880 TI - Individual patterns of functional reorganization in the human cerebral cortex after capsular infarction. AB - We have previously shown bilateral activation of motor pathways and the recruitment of additional motor areas in studies of groups of patients with recovery from motor stroke. We have now developed a new positron emission tomographic technique to measure the changes in regional cerebral blood flow elicited during a motor task in individual patients, relative to the cerebral activation found in normal subjects. The patterns of cerebral activation in each of 8 individual patients with capsular lesions of the pyramidal tract and complete recovery from hemiplegia are described by comparison with the pattern found in a representative sample of 10 normal subjects. We found a large ventral extension of the hand field of the contralateral (sensori)motor cortex in all patients with lesions of the posterior limb of the internal capsule. Greater activation than in normal subjects was found in variable combinations of the supplementary motor areas, the insula, the frontal operculum, and the parietal cortex. Structures belonging to motor pathways ipsilateral to the recovered limb were also more activated in the patients than in normal subjects. However, additional activation of the ipsilateral (sensori)motor cortex was only found in the 4 patients who exhibited associated movements of the unaffected hand when the recovered hand performed the motor task. We conclude that recovery from motor stroke due to striatocapsular damage is associated with individually different patterns of functional reorganization of the brain. These patterns are dependent on the site of the subcortical lesion and the somatotopic organization of the pyramidal tract, both of which may determine the precise potential for recovery of limb function following this type of brain injury. PMID- 8434881 TI - Synapse loss in the temporal lobe in Alzheimer's disease. AB - The temporal lobe is a well-documented area showing neuropathological and neurochemical changes in Alzheimer's disease (AD). Autopsy tissue was obtained from the superior temporal (Brodmann area 22) and the middle temporal (Brodmann area 21) regions of the cortex from patients with AD (n = 10; postmortem time < 13 hr) and age-matched control subjects (n = 10; postmortem time < 13 hr). Ultrastructural examination of the tissue revealed a highly significant AD related decline in synaptic numbers in lamina III and V in both the superior and the middle temporal gyrus. Both normal control and AD tissue samples demonstrated a significant negative correlation between the number of synapses and the synapse size, as indexed by the length of the postsynaptic density. This change in synaptic size appears to compensate for the loss of synaptic numbers when viewed in terms of total synaptic contact area. Although the AD tissue showed an average 30% decline in synaptic numbers, the total synaptic contact area remained largely unchanged in both regions of the cortex. There were no significant correlations with age, postmortem time, or number of plaques observed in these areas. The loss of synaptic contacts in AD does not appear to be isolated to a particular cortical region or lamina. PMID- 8434882 TI - Human class I major histocompatibility complex transgene prevents virus-induced demyelination in susceptible mutant B10.D2dml mice. AB - Theiler's murine encephalomyelitis virus (TMEV) induces immune-mediated demyelination in susceptible strains of mice, providing an excellent model for multiple sclerosis. Class I genes within the major histocompatibility complex locus (H-2D region) play a major role in determining whether strains of mice develop chronic demyelination and TMEV persistence. B10.D2dml mice with deletion in the 3' end of Dd and the 5' end of Ld genes develop the most prominent demyelination in comparison with resistant B10.D2 mice with normal complementation of H-2D region genes. We tested whether expression of a class I human transgene (HLA-B27) would modulate virus-induced demyelination in mutant B10.D2dml mice. Transgenic B10.D2dml (HLA-B27+) mice infected with virus showed dramatic decrease in the extent of demyelination (p < 0.0001) and virus antigen expression in spinal cord compared with littermate controls without the human class I transgene. These experiments demonstrate that transgenic expression of a human class I major histocompatibility complex locus molecule can prevent demyelination induced by a virus in mutant mice. PMID- 8434883 TI - "Signing tics"--insights into the pathophysiology of symptoms in Tourette's syndrome. AB - We describe the case of a young woman with Tourette's syndrome who incorporated sign language into her tic behavior. Sign language was used in complex "phonic tics" such as swearing, echoing what others said, or repeating what she said, read, or thought. We suggest the descriptive terms "coprolaliopraxia," "echolaliopraxia," and "palilaliopraxia" to denote these symptoms. The incorporation of such complex, learned movements into the repertoire of hyperkinesias further emphasizes the complicated association between purposeful and automatic execution of movements comprising tic behavior. This case also provides strong evidence against the suggestion that obscenities vocalized in Tourette's syndrome are due to a random generation of high-probability sequences of letters or phonemes. PMID- 8434884 TI - Crossed aphasia with visceral situs inversus. AB - A patient presenting the association of anomalous cerebral dominance for language, as revealed by crossed aphasia, and partial visceral situs inversus is described. Although it cannot be excluded that the two abnormalities coincided by chance, it is suggested that they both resulted from a single aberration of development. PMID- 8434885 TI - Signal loss in the motor cortex on magnetic resonance images in amyotrophic lateral sclerosis. AB - Three of 7 patients with amyotrophic lateral sclerosis had bilateral signal loss confined to the motor cortex on T2-weighted magnetic resonance images. None of the control subjects had this abnormality. Although not present in every patient, this finding might reflect the primary pathological process of the motor cortex in amyotrophic lateral sclerosis. PMID- 8434886 TI - Delayed peripartum vasculopathy: cerebral eclampsia revisited. AB - Over a 2-year period, we treated 4 postpartum patients with acute neurologic problems appearing 4 to 9 days after delivery. Three patients either had no proteinuria or edema and therefore did not meet all accepted clinical criteria for the diagnosis of eclampsia. Magnetic resonance imaging (MRI) of the brain in all patients demonstrated high-signal foci most prominent in the parieto occipital regions and the subcortical white matter. Cerebral angiogram in 2 patients revealed diffuse vasospasm. In 3 patients, MRI abnormalities resolved. MRI and angiographic abnormalities in our patients are identical to those of patients meeting accepted criteria for eclampsia. Our experience suggests that the current criteria for the diagnosis of eclampsia are too stringent, both in terms of clinical picture and days postpartum to cerebral manifestations. PMID- 8434887 TI - Terfenadine-induced tremor. PMID- 8434888 TI - GAP-43 immunoreactivity is detected in the nerve terminals of patients with amyotrophic lateral sclerosis. PMID- 8434889 TI - Human immunodeficiency virus-infected macrophages, gp120, and N-methyl-D aspartate receptor-mediated neurotoxicity. PMID- 8434890 TI - From psychological stress to the emotions: a history of changing outlooks. PMID- 8434891 TI - Social cognition and social perception. PMID- 8434892 TI - Mammalian brain substrates of aversive classical conditioning. AB - In this review, we have examined recent studies that have successfully identified neural circuits necessary for nonspecific and specific conditioned responses. This success is due in large part to the advantages of the classical conditioning paradigm for controlling stimuli and responses. Clearly, this research does not attempt to account for all forms of memory. The power of this approach is demonstrated by the distinction between essential and nonessential memory traces or engrams. Essential memory traces represent the circuitry responsible for forming the association in classical conditioning. Nonessential memory traces do not represent the essential association, but they are important for facilitating, adapting, and modifying the final performance of the learned behavior. The search for the engram for any learned behavior has been viewed with skepticism by some investigators who quote Karl Lashley: "This series of experiments has yielded a good bit of information about what and where the memory is not. It has discovered nothing directly of the real nature of the engram" (1950, pp. 477-78). However, these authors neglect to quote Lashley fully, for even he was less pessimistic about that search than in normally recognized. He continued, "I sometimes feel, in reviewing the evidence on the localization of the memory trace, that the necessary conclusion is that learning just is not possible. It is difficult to conceive of a mechanism which can satisfy the conditions set for it. Nevertheless, in spite of such evidence against it, learning does sometimes occur" (1950, pp. 477-78, emphasis added). Learning does indeed occur, and its neurobiological substrates can be localized. PMID- 8434893 TI - Information processing models: microscopes of the mind. PMID- 8434894 TI - The structure and organization of memory. PMID- 8434895 TI - Psychoneuroimmunology: conditioning and stress. AB - The acquisition and extinction of the conditioned suppression or enhancement of one or another parameter of antigen-specific and nonspecific defense system responses have been documented in different species under a variety of experimental conditions. Similarly, stressful stimulation influences antigen specific as well as nonspecific reactions. Moreover, both conditioning and stressful stimulation exert biologically meaningful effects in the sense that they can alter the development and/or progression of what are presumed to be immunologically mediated pathophysiologic processes. These are highly reproducible phenomena that illustrate a functional relationship between the brain and the immune system. However, the extent to which one can generalize from one stressor to another or from one parameter of immunologic reactivity to another is limited. Few generalizations are possible because the direction and/or magnitude of the effects of conditioning and "stress" in modulating immune responses clearly depend on the quality and quantity of the behavioral interventions, the quality and quantity of antigenic stimulation, the temporal relationship between behavioral and antigenic stimulation, the nature of the immune response and the immune compartment in which it is measured, the time of sampling, a variety of host factors (e.g. species, strain, age, sex), and interactions among these several variables. It seems reasonable to assume that the immunologic effects of behaviorally induced neural and endocrine responses depend on (interact with) the concurrent immunologic events upon which they are superimposed. Conversely, the efficacy of immunologic defense mechanisms seems to depend on the neuroendocrine environment on which they are superimposed. We seek to determine when and what immunologic (or neuroendocrine) responses could be affected by what neuroendocrine (or immunologic) circumstances. We therefore need studies that provide a parametric analysis of the stimulus conditions, the neuroendocrine and/or immunologic state upon which they are superimposed, and the responses that are being sampled. The neural or neuroendocrine pathways involved in the behavioral alteration of immune responses are not yet known. Both conditioning and stressor-induced effects have been hypothesized to result from the action of adrenocortical steroids, opioids, and catecholamines, among others. Indeed, all of these have been implicated in the mediation of some immunologic effects observed under some experimental conditions. We assume that different conditioning and stressful environmental circumstances induce different constellations of neuroendocrine responses that constitute the milieu within which ongoing immunologic reactions and the response to immunologic signals occur.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8434896 TI - Social-cognitive mechanisms in the development of conduct disorder and depression. PMID- 8434897 TI - Social foundations of cognition. PMID- 8434898 TI - Animal behavior: a continuing synthesis. PMID- 8434899 TI - Health is empowerment. AB - A consideration of health in relation to global and diverse social and economic contexts forces nurses to reexamine the centrality of health in the discipline of nursing and to confront the issue of whether health is a personal matter. In this article, the authors review development of the concept of health in nursing science, discuss the limitations of some current definitions in addressing diverse clients, and challenge members of the discipline to develop a contextualized definition of health congruent with societal needs and the mission of nursing. PMID- 8434900 TI - The power of the name. AB - An integral part of any research study is the assignment of names to phenomena of interest. The linguistic nuances accompanying names are frequently neglected, with a resulting significant affect on nursing research and on the tenor of nursing knowledge. Concept analysis is an important strategy for surmounting the difficulties associated with the process of choosing and modifying names. Examples of the naming process in two areas of nursing research are used to illustrate the influence of concept analysis on the development of nursing knowledge. PMID- 8434901 TI - The intersection of technology and care in the ICU. AB - In this article the author describes the paradoxical nature of the relationship between technology and care in the ICU. Although technology enhances care by expanding the repertoire of competent nurses' responses to the patient, it simultaneously alienates nurse and patient, hence inhibiting care. This occurs when nurses and patients have different understandings of technology and when the nurse identifies with the values imposed by technology at the expense of acknowledging her own and the patient's vulnerability. PMID- 8434902 TI - Informal carers: a Marxist analysis of social, political, and economic forces underpinning the role. AB - Increasingly, families are being called to provide care to their elderly family members. Nursing has an important role to play in enabling families to assume such responsibilities. In this article, however, it is argued that nursing needs to examine its goals for nursing care and approaches to care delivery in their broader social, political, and economic context. Marxist theory is introduced and used to raise questions about taken-for-granted aspects of nursing practice and trends in health policy as they relate to family carers for the elderly. The article specifically examines assumptions about family, women, and household economies that are inherent in traditional nursing theory. It is argued that nursing needs to move its focus of action beyond work at the individual and family level to include work at system and policy levels. To do so, nursing must examine theoretical perspectives that enable such an inquiry into practice. PMID- 8434903 TI - The Triandis model for the study of health and illness behavior: a social behavior theory with sensitivity to diversity. AB - The Triandis model of social behavior offers exceptional promise to nurse researchers whose goal is to achieve cultural sensitivity in their research investigations. The model includes six components: consequential beliefs, affect, social influences, previous behavioral habits, physiologic arousal, and facilitating environmental resources. A directed methodology to include culture relevant items in the measurement of each of these model components allows researchers to capture the diverse explanations of health and illness behavior that might pertain in diverse populations. Researchers utilizing the model can achieve theory-based explanations of differences they observe by gender, race/ethnicity, social class, and sexual orientation. The Triandis model can provide studies to target variables for future intervention studies, as well as highlight areas for needed political action to equalize access to and delivery of nursing care. PMID- 8434904 TI - Self-care myth reconsidered. AB - Self-care ideology and theory can do much to shape the development of health policy and the organization and delivery of health care. From a critical social perspective, self-care theory can be seen as an attempt to sustain the illusion of individual choice in contemporary health care delivery. Understanding the dominance of individual responsibility for health that permeates the essence of self-care theory provides a way of understanding a vision of thought and practice that currently exists within the discipline of nursing. This article attempts to elucidate the social and political construction of nursing knowledge with a view to self-care. PMID- 8434905 TI - The unintended consequences of a male professional ideology for the development of nursing education. AB - At the turn of this century, early leaders of nursing education in the United States looked at the success of physicians in creating medicine's acceptance as a "profession." Trying to emulate this model, female nurses embraced a culturally and socially defined medical, male-oriented professional ideology that equated being professional with being scientific. In this article, an exploration of the unintended and unacknowledged consequences of the nurse leader's actions reveals how adherence to this professional ideology has divided nurses and confined its proponents to professionally limiting and self-defeating values. PMID- 8434906 TI - Detection of Escherichia coli in sewage and sludge by polymerase chain reaction. AB - A method in which the polymerase chain reaction (PCR) was used was developed to amplify either a uidA gene fragment or a 16S rRNA gene fragment from Escherichia coli in sewage and sludge. Because of interference caused by humic acidlike substances, crude DNA extracts were purified with a Sephadex G-200 spun column before the PCR was begun. A Southern analysis in which a nonradioactive chemiluminescent method was used was performed to confirm the presence of PCR products. The sensitivity of detection for PCR products when the chemiluminescent method was used was determined to be 30 ag of E. coli genomic DNA template. In seeded sludge, the PCR amplified the target DNA from 80 E. coli cells per g of sludge and 50 Shigella dysenteriae cells per g of sludge. Because only 0.05 aliquot of a sludge extract was used for the PCR, we deduced that the PCR detected target DNA equivalent to the DNA of 2.5 to 4 cells in the extract. The PCR amplified the uidA fragment from diluted sewage influents and effluents containing E. coli cells. Therefore, the PCR performed with a chemiluminescent gene probe can be used to detect the presence of potentially pathogenic microorganisms in sewage and sludge. This technique can be expanded to permit direct detection of pathogenic microorganisms in water samples, thus leading to enhanced public health protection. PMID- 8434907 TI - Evaluation of commercial presence-absence test kits for detection of total coliforms, Escherichia coli, and other indicator bacteria. AB - Evaluations of several commercial presence-absence (P-A) test kits were performed over a 6-month period in 1990 by using the Ontario Ministry of the Environment (MOE) P-A test for comparison. The general principles of the multiple-tube fermentation technique formed the basis for conducting the product evaluations. Each week, a surface water sample was diluted and inoculated into 25 99-ml dilution blanks for each of three dilutions. The inoculated dilution blanks from each dilution series were randomly sorted into sets of five. Three of these sets were inoculated into the P-A test kits or vice versa, as required. The other two sets were passed through membrane filters, and one set of five membrane filters was placed onto m-Endo agar LES to give replicate total coliform counts and the other set was placed onto m-TEC agar to give replicate fecal coliform results. A statistical analysis of the results was performed by a modified logistic transform method, which provided an improved way to compare binary data obtained from the different test kits. The comparative test results showed that three of the four commercial products tested gave very good levels of recovery and that the fourth commercial product gave only fair levels of recovery when the data were compared with the data from MOE P-A tests and membrane filter tests. P-A bottles showing positive results after 18 h of incubation that were subcultured immediately in ECMUG tubes frequently could be confirmed as containing total coliforms, fecal coliforms, or Escherichia coli after 6 h of incubation; thus, the total incubation time was only 24 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8434908 TI - Performance of anaerobic granules for degradation of pentachlorophenol. AB - Anaerobic granules degrading pentachlorophenol (PCP) with specific PCP removal activity up to 14.6 mg/g of volatile suspended solids per day were developed in a laboratory-scale anaerobic upflow sludge blanket reactor at 28 degrees C, by using a mixture of acetate, propionate, butyrate, and methanol as the carbon source. The reactor was able to treat synthetic wastewater containing 40 to 60 mg of PCP per liter at a volumetric loading rate of up to 90 mg/liter of reactor volume per day, with a hydraulic retention time of 10.8 to 15 h. PCP removal of more than 99% was achieved. Results of adsorption of PCP by granular biomass indicated that the PCP removal by the granules was due to biodegradation rather than adsorption. A radiotracer assay demonstrated that the PCP-degrading granules mineralized [14C]PCP to 14CH4 and 14CO2. Toxicity test results indicated that syntrophic propionate degraders and acetate-utilizing methanogens were more sensitive to PCP than syntrophic butyrate degraders. The PCP-degrading granules also exhibited a higher tolerance to the inhibition caused by PCP for methane production and degradation of acetate, propionate, and butyrate, compared with anaerobic granules unadapted to PCP. PMID- 8434909 TI - Inhibition of ruminal cellulose fermentation by extracts of the perennial legume cicer milkvetch (Astragalus cicer). AB - Cicer milkvetch (Astragalus cicer L.) is a perennial legume used as a pasture or rangeland plant for ruminants. A study was undertaken to determine whether reported variations in its ruminal digestibility may be related to the presence of an antinutritive material. In vitro fermentation of neutral detergent fiber (NDF) of cicer milkvetch by mixed rumen microflora was poorer than was the fermentation of NDF in alfalfa (Medicago sativa L.). Fermentation of cicer milkvetch NDF was improved by preextraction of the ground herbage with water for 3 h at 39 degrees C. Such water extracts selectively inhibited in vitro fermentation of pure cellulose by mixed ruminal microflora and by pure cultures of the ruminal bacteria Ruminococcus flavefaciens FD-1 and Fibrobacter succinogenes S85. Inhibition of the cellulose fermentation by mixed ruminal microflora was dependent upon the concentration of cicer milkvetch extract and was overcome upon prolonged incubation. Pure cultures exposed to the extract did not recover from inhibition, even after long incubation times, unless the inhibitory agent was removed (viz., by dilution of inhibited cultures into fresh medium). The extract did not affect the fermentation of cellobiose by R. flavefaciens but did cause some inhibition of cellobiose fermentation by F. succinogenes. Moreover, the extracts did not inhibit hydrolysis of crystalline cellulose, carboxymethyl cellulose, or p-nitrophenylcellobioside by supernatants of these pure cultures of cellulolytic bacteria or by a commercial cellulase preparation from the fungus Trichoderma reesei. The agent caused cellulose adherent cells to detach from cellulose fibers, suggesting that the agent may act, at least in part, by disrupting the glycocalyx necessary for adherence to, and rapid digestion of, cellulose. PMID- 8434910 TI - Effect of phenotypic plasticity on epiphytic survival and colonization by Pseudomonas syringae. AB - The bacterial epiphyte Pseudomonas syringae MF714R was cultured on agar or in broth or collected from colonized leaves; it was then inoculated onto greenhouse grown bean plants incubated in a growth chamber at low relative humidity or in the field or onto field-grown bean plants. Cells cultured in liquid medium survived the least well after inoculation of leaf surfaces under all conditions. Cells cultured in solid medium exhibited the highest percent survival and desiccation tolerance in the growth chamber but generally survived less well in the field than did cells harvested from plants. Cells harvested from plants and inoculated onto plants in the field usually exhibited the highest percent survival, started to increase in population earlier, and reached a higher number than did cells cultured in vitro. Differences in field survival were apparently not attributable to differential UV tolerance. The observed effects of phenotypic plasticity on epiphytic survival and colonization should be considered in risk assessment studies, in studies of bacterial epidemiology, and in the use of microbial antagonists for biological pest control. PMID- 8434911 TI - Population genetics of human, animal, and environmental Yersinia strains. AB - Multilocus enzyme electrophoresis was used to analyze 244 strains of nine Yersinia species isolated from the environment, animals, and humans at 18 genes encoding metabolic enzymes. All 18 enzymes were polymorphic. Among the 137 electrophoretic types (ETs) distinguished, the mean allelic diversity per locus was 0.531. Yersinia frederiksenii ETs were divided into three major clusters that were separated by a large genetic distance, and one ET was more closely related to Yersinia enterocolitica. Thus, strains classically identified as Y. frederiksenii may represent more than one species. Furthermore, two strains identified as Yersinia kristensenii proved to be more closely related to Yersinia mollaretii. Environmental strains formed independent groups. A very interesting ET consisting of as many as 61 isolates of Yersinia enterocolitica was detected, and the epidemiologic relevance of this ET is discussed. Human strains of Y. enterocolitica biotype 4 and Yersinia pseudotuberculosis were recognized as being closely related to animal strains of the same species. Therefore, animal strains of these two species may be considered potential human pathogens. PMID- 8434912 TI - Roles of N-acetylglutaminylglutamine amide and glycine betaine in adaptation of Pseudomonas aeruginosa to osmotic stress. AB - The mechanism of osmotic stress adaptation in Pseudomonas aeruginosa PAO1 was investigated. By using natural abundance 13C nuclear magnetic resonance spectroscopy, osmotically stressed cultures were found to accumulate glutamate, trehalose, and N-acetylglutaminylglutamine amide, an unusual dipeptide previously reported only in osmotically stressed Rhizobium meliloti and Pseudomonas fluorescens. The intracellular levels of these osmolytes were dependent on the chemical composition and the osmolality of the growth medium. It was also demonstrated that glycine betaine, a powerful osmotic stress protectant, participates in osmoregulation in this organism. When glycine betaine or its precursors, phosphorylcholine or choline, were added to the growth medium, growth rates of cultures in 0.7 M NaCl were increased more than threefold. Furthermore, enhancement of growth could be observed with as little as 10 microM glycine betaine or precursor added to the medium. Finally, the mechanism of osmotic stress adaptation of two clinical isolates of P. aeruginosa was found to be nearly identical to that of the laboratory strain PAO1 in all aspects studied. PMID- 8434914 TI - Esterase electrophoretic polymorphism of human and animal strains of Clostridium perfringens. AB - Esterase electrophoretic polymorphism in human and animal strains of Clostridium perfringens was studied by using polyacrylamide-agarose gel electrophoresis. Five types of esterases, designated E-I to E-V and defined by their hydrolytic specificities toward five synthetic substrates, were found in protein extracts of bacteria grown without glucose (glucose-containing media allowed only the expression of esterase E-I). Mobility variants of esterase E-I, which hydrolyzes alpha- and beta-naphthyl acetates and butyrates, were used as a basis for the distribution of strains into 11 zymogroups. When all five types of esterases and their electrophoretic variants were considered, 77 electrophoretic types (ETs) could be described for the 89 strains tested. Animal strains did not constitute a distinctive subpopulation, as revealed by their distribution in the zymogroups and by clustering analysis. Statistical analysis also emphasized the importance of esterase E-IV (which hydrolyzes only naphthyl acetates) and esterase E-V (which hydrolyzes only alpha-naphthyl acetate) in clustering by the relatedness of the ETs. ETs allowed the epidemiological characterization of stool isolates recovered from elderly inpatient residents and from adolescent chronic-care psychiatric patients. These results indicate that esterase electrophoretic typing may be a marker for epidemiological and ecological analyses. PMID- 8434913 TI - Purification of a 40-kilodalton methyltransferase active in the aflatoxin biosynthetic pathway. AB - The penultimate step in the aflatoxin biosynthetic pathway of the filamentous fungi Aspergillus flavus and A. parasiticus involves conversion of sterigmatocystin to O-methylsterigmatocystin. An S-adenosylmethionine-dependent methyltransferase that catalyzes this reaction was purified to homogeneity (> 90%) from 78-h-old mycelia of A. parasiticus SRRC 163. Purification of this soluble enzyme was carried out by five soft-gel chromatographic steps: cell debris remover treatment, QMA ACELL chromatography, hydroxylapatite-Ultrogel chromatography, DEAE-Spherodex chromatography, and Octyl Avidgel chromatography, followed by MA7Q high-performance liquid chromatography. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of the protein peak from this step on silver staining identified a single band of approximately 40 kDa. This purified protein was distinct from the dimeric 168-kDa methyltransferase purified from the same fungal strain under identical growth conditions (D. Bhatnagar, A. H. J. Ullah, and T. E. Cleveland, Prep. Biochem. 18:321-349, 1988). The chromatographic behavior and N-terminal sequence of the 40-kDa enzyme were also distinct from those of the 168-kDa methyltransferase. The molar extinction coefficient of the 40-kDa enzyme at 278 nm was estimated to be 4.7 x 10(4) M-1 cm-1 in 50 mM potassium phosphate buffer (pH 7.5). PMID- 8434915 TI - Effects of a lignin peroxidase-expressing recombinant, Streptomyces lividans TK23.1, on biogeochemical cycling and the numbers and activities of microorganisms in soil. AB - A recombinant actinomycete, Streptomyces lividans TK23.1, expressing a pIJ702 encoded extracellular lignin peroxidase gene cloned from the chromosome of Streptomyces viridosporus T7A, was released into soil in flask- and microcosm scale studies to determine its effects on humification and elemental cycling and on the numbers, types, and activities of microorganisms native to the soil. Strain TK23.1 had been shown previously to transiently increase the rate of organic carbon mineralization in soil via an effect that was recombinant specific and particularly significant in nonsterile soils already possessing an active microflora. The results of this study confirmed the previous findings and showed that additional effects were measurable upon release of the recombinant strain TK23.1 into unamended soil and into soil amended with lignocellulose. In addition to a transient enhancement of carbon mineralization, the recombinant affected soil pH, the rate of incorporation of carbon into soil humus fractions, nitrogen cycling, the relative populations of some microbial groups, and also certain soil enzyme activities. Whereas the survival or persistence in soil of the recombinant TK23.1 strain and that of its parent, TK23, were similar, the observed effects on microbial numbers, types, and activities were recombinant specific and did not occur when the parental strain was released into soil. All of the measured effects were transient, generally lasting for only a few days. While the effects were statistically significant, their ecological significance appears to be minimal. This is the first report showing that a recombinant actinomycete can affect the microbial ecology of soil in ways that can be readily monitored by using a battery of microbiological, enzymological, and chemical assays. PMID- 8434916 TI - Multiplex polymerase chain reaction for detection and differentiation of the microbial insecticide Bacillus thuringiensis. AB - A rapid identification of Bacillus thuringiensis strains was established by using multiplex polymerase chain reaction (PCR). Primers of high homology specific to regions within genes encoding three major classes of B. thuringiensis crystal proteins were used to generate a PCR product profile characteristic of each strain of B. thuringiensis subsp. kurstaki. Differentiation among these strains was made on the basis of the electrophoretic pattern of the PCR products. Known B. thuringiensis subsp. kurstaki strains as well as unidentified strains isolated from insect cadavers were analyzed by PCR. Small amounts of crude sample lysates were assayed in a two-step PCR containing five primers capable of distinguishing between the strains giving products of 1,500, 858, and 653 bp for the CryIA(a) CryIA(b), and CryIA(c) genes, respectively. The method can be applied to rapidly detect the strains of B. thuringiensis subsp. kurstaki in commercial formulations and in the field. PMID- 8434917 TI - Degradation of 2-chloroallylalcohol by a Pseudomonas sp. AB - Three Pseudomonas strains capable of utilizing 2-chloroallylalcohol (2 chloropropenol) as the sole carbon source for growth were isolated from soil. The fastest growth was observed with strain JD2, with a generation time of 3.6 h. Degradation of 2-chloroallylalcohol was accompanied by complete dehalogenation. Chloroallylalcohols that did not support growth were dechlorinated by resting cells; the dechlorination level was highest if an alpha-chlorine substituent was present. Crude extracts of strain JD2 contained inducible alcohol dehydrogenase activity that oxidized mono- and dichloroallylalcohols but not trichloroallylalcohol. The enzyme used phenazine methosulfate as an artificial electron acceptor. Further oxidation yielded 2-chloroacrylic acid. The organism also produced hydrolytic dehalogenases converting 2-chloroacetic acid and 2 chloropropionic acid. PMID- 8434918 TI - Use of the polymerase chain reaction and fluorescent-antibody methods for detecting viable but nonculturable Shigella dysenteriae type 1 in laboratory microcosms. AB - Epidemiological studies of shigellosis in Bangladesh have demonstrated that surface-water sources can act as foci of infection. Studies of laboratory microcosms have shown that shigellae become nonculturable but remain viable when exposed to environmental samples of water. The present study was carried out to detect viable but nonculturable Shigella dysenteriae 1 from laboratory microcosms by the polymerase chain reaction and the fluorescent-antibody techniques. S. dysenteriae 1 was inoculated into laboratory microcosms consisting of water samples collected from ponds, lakes, rivers, and drains in Bangladesh. The survival of S. dysenteriae in microcosms was assessed by viable counting on MacConkey agar. After 2 to 3 weeks, S. dysenteriae 1 became nonculturable but remained viable. After 6 weeks, this nonculturable but viable S. dysenteriae 1 was detected by both the polymerase chain reaction and the fluorescent-antibody methods. The viable but nonculturable state of S. dysenteriae 1 demonstrated in this study may be important for understanding the epidemiology of shigellosis. PMID- 8434919 TI - Rapid identification of Vibrio vulnificus on nonselective media with an alkaline phosphatase-labeled oligonucleotide probe. AB - An oligonucleotide DNA probe (VVAP) was constructed from a portion of the Vibrio vulnificus cytolysin gene (hylA) sequence and labeled with alkaline phosphatase covalently linked to the DNA. Control and environmental isolates probed with VVAP showed an exact correlation with results obtained with a plasmid DNA probe (derived from pCVD702) previously described as having 100% specificity and sensitivity for this organism. Identification of V. vulnificus strains was confirmed independently by analysis of the cellular fatty acid composition and by API 20E. Naturally occurring V. vulnificus bacteria were detected without enrichment or selective media by VVAP in unseeded oyster homogenates and seawater collected from a single site in Chesapeake Bay during June at concentrations of 6 x 10(2) and 2 x 10(1) bacteria per ml, respectively. V. vulnificus bacteria were also enumerated by VVAP in oysters seeded with known concentrations of bacteria and plated on nonselective medium. The VVAP method provides a rapid, accurate means of identifying and enumerating V. vulnificus in seawater and oysters without the use of selective media or additional biochemical tests. PMID- 8434920 TI - Cyclodextrins as carriers of cholesterol and fatty acids in cultivation of mycoplasmas. AB - The design of fully or partly defined media for mycoplasma cultivation involves the need to provide the essential lipids, cholesterol and long-chain fatty acids, in an assimilable and nontoxic form. This study introduces cyclodextrins (CDs) as carriers of these lipids, thus suggesting alternatives to serum or bovine serum albumin (BSA). The effects of beta-CD and two forms of chemically modified beta CD, dimethyl-beta-CD (Dimeb) and hydroxypropyl-beta-CD (Hyprob), on the growth of Mycoplasma capricolum and Acholeplasma laidlawii were investigated in a basal medium as well as in serum- and BSA-supplemented media. beta-CD was found to inhibit the growth of the sterol-requiring M. capricolum in both serum and BSA media, but it stimulated the growth of the sterol-independent A. laidlawii. Inhibition by beta-CD was explained by its capacity to form a water-insoluble CD cholesterol complex, thus rendering it unavailable to the cells. Dimeb, despite its strong complexing ability for lipids, was found to be toxic to all mycoplasma species in both liquid cultures and agar diffusion susceptibility tests. In sharp contrast to beta-CD and Dimeb, Hyprob (with a degree of substitution of 4.2) added at 5 and 10 mM to a basal medium supplemented with lipids permitted growth of M. capricolum. Comparison of growth curves in the two conventional serum and BSA media with those in two Hyprob media revealed comparable growth and growth rates. PMID- 8434921 TI - Comparison of methods for estimating the biomass of three food-borne fungi with different growth patterns. AB - To evaluate the effectiveness of steps taken to reduce the growth of molds in food and feed, methods that can accurately quantify the degree of fungal contamination of solid substrates are needed. In this study, the ergosterol assay has been evaluated by comparing the results of this assay with spore counts and hyphal length measurements made with a microscope and with CFU counts. Three fungi with different growth patterns during cultivation on a synthetic agar substrate were used in these experiments. For the nonsporulating Fusarium culmorum, there was good agreement between changes in hyphal length, CFU, and ergosterol content. Penicillium rugulosum and Rhizopus stolonifer produced many spores, and the production of spores coincided with large increases in CFU but not with increases in hyphal length or ergosterol content. Spores constituted between 3 and 5% of the total fungal mass. Changes in ergosterol level were closely related to changes in hyphal length. It was concluded that ergosterol level is a suitable marker for use in quantitatively monitoring fungal growth in solid substrates. PMID- 8434922 TI - Rapid polymerase chain reaction method for detection of Vibrio cholerae in foods. AB - The polymerase chain reaction was used to selectively amplify sequences within the cholera toxin operon from Vibrio cholerae O1. Oysters, crabmeat, shrimp, and lettuce were seeded with V. cholerae and then homogenized or washed with alkaline peptone water, followed by short-term (6- to 8-h) enrichment. A detection limit of as few as 1 V. cholerae CFU per 10 g of food was obtained with amplification reactions from crude bacterial lysates. The method is extremely rapid and obviates the need for DNA isolation from a variety of complex food matrices. PMID- 8434923 TI - Metabolism of tetralin (1,2,3,4-tetrahydronaphthalene) in Corynebacterium sp. strain C125. AB - Corynebacterium sp. strain C125, originally isolated on o-xylene, was selected for its ability to grow on tetralin (1,2,3,4-tetrahydronaphthalene) as the sole source of carbon and energy. The catabolism of tetralin in Corynebacterium sp. strain C125 was shown to proceed via initial hydroxylation of the benzene nucleus at positions C-5 and C-6, resulting in the formation of the corresponding cis dihydro diol. Subsequently, the dihydro diol was dehydrogenated by a NAD dependent dehydrogenase to 5,6,7,8-tetrahydro-1,2-naphthalene diol. The aromatic ring was cleaved in the extradiol position by a catechol-2,3-dioxygenase. The ring fission product was subject to a hydrolytic attack, resulting in the formation of a carboxylic acid-substituted cyclohexanone. This is the first report of the catabolism of tetralin via degradation of the aromatic moiety. PMID- 8434924 TI - Role of copper resistance in competitive survival of Pseudomonas fluorescens in soil. AB - A copper-resistant strain (09906) of Pseudomonas fluorescens that was isolated from a citrus grove soil is being investigated as a biological control agent for Phytophthora root rot. Since citrus grove soils in California are often contaminated with copper from many years of copper fungicide applications, the role of copper resistance in survival of strain 09906 was investigated. Three copper-sensitive Tn5 mutants were obtained with insertions in different chromosomal DNA regions. These insertions were not in the chromosomal region that hybridized with the copper resistance operon (cop) cloned from Pseudomonas syringae. A copper-sensitive mutant survived as well as the wild type in a sterile loamy sand without added copper, but with 10 and 15 micrograms of CuSO4 added per g of soil, populations of the copper-sensitive mutant were 27- and 562 fold lower, respectively, than that of the wild type after a 25-day period. In a sterilized citrus grove soil, populations of the copper-sensitive mutant and wild type strain were similar, but in nonsterile citrus soil, populations of the copper-sensitive mutant were 112-fold lower than the wild type after 35 days. These data suggest that copper resistance genes can be important factors in persistence of P. fluorescens in soil contaminated with copper. In addition, these genes appear to play a role in competitive fitness, even in soils with a low copper content. PMID- 8434925 TI - Survival differences among freeze-dried genetically engineered and wild-type bacteria. AB - Because the death mechanisms of freeze-dried and air-dried bacteria are thought to be similar, freeze-drying was used to investigate the survival differences between potentially airborne genetically engineered microorganisms and their wild types. To this end, engineered strains of Escherichia coli and Pseudomonas syringae were freeze-dried and exposed to air, visible light, or both. The death rates of all engineered strains were significantly higher than those of their parental strains. Light and air exposure were found to increase the death rates of all strains. Application of death rate models to freeze-dried engineered bacteria to be released into the environment is discussed. PMID- 8434926 TI - Development and use of a selective medium for isolation of Leuconostoc spp. from vegetables and dairy products. AB - A selective medium (LUSM medium) for the isolation of Leuconostoc spp. was developed. This medium contained 1.0% glucose, 1.0% Bacto Peptone (Difco), 0.5% yeast extract (BBL), 0.5% meat extract (Difco), 0.25% gelatin (Difco), 0.5% calcium lactate, 0.05% sorbic acid, 75 ppm of sodium azide (Sigma), 0.25% sodium acetate, 0.1% (vol/vol) Tween 80, 15% tomato juice, 30 micrograms of vancomycin (Sigma) per ml, 0.20 microgram of tetracycline (Serva) per ml, 0.5 mg of cysteine hydrochloride per ml, and 1.5% agar (Difco). LUSM medium was used successfully for isolation and enumeration of Leuconostoc spp. in dairy products and vegetables. Of 116 colony isolates obtained from fresh raw milk, curdled milk, or various vegetables, 115 were identified as members of the genus Leuconostoc. A total of 89 of these isolates were identified to species; 13.5% of the isolates were Leuconostoc cremoris, 7.9% were Leuconostoc mesenteroides subsp. mesenteroides, 11.2% were Leuconostoc mesenteroides subsp. dextranicum, 16.9% were Leuconostoc mesenteroides subsp. paramesenteroides, 10.1% were leuconostoc lactis, and 40.4% were Leuconostoc oenos. When we compared the counts obtained for two Leuconostoc strains, Leuconostoc dextranicum 181 and L. cremoris JLL8, on MRS agar and LUSM medium, we found no significant difference between the values obtained on the two media. PMID- 8434927 TI - Genetic basis of tetracycline resistance in food-borne isolates of Listeria innocua. AB - Eleven of 12 tetracycline-resistant Listeria innocua strains, isolated from chicken or turkey frankfurters and mozzarella cheese, were shown to carry DNA sequences which hybridized with the Tet M probe; of these, two strains also hybridized with Tet K. The remaining strain hybridized with the Tet K probe only. The Tet M determinant appeared to be located on the chromosome; in one case, it was transferable by conjugation to recipients Listeria monocytogenes, Listeria ivanovii, and Enterococcus faecalis. PMID- 8434928 TI - Comparison of conventional and reversed phage typing procedures for identification of Listeria spp. AB - Of 225 Listeria isolates evaluated, 199 had the same bacteriophage patterns by both the conventional (A. Audurier, A.G. Taylor, B. Carbonelle, and J. McLaughlin, Clin. Invest. Med. 7:229-232, 1984) and the new, easier to apply, "reversed" (M. J. Loessner, Appl. Environ. Microbiol. 57:882-884, 1991) phage typing procedures, 5 had different phage reactions, and the remaining 21 isolates were untypeable. Thus, the overall typeability rate was 90.7%, and 97.6% of the typeable isolates had the same phage patterns by both procedures. PMID- 8434929 TI - Purification and properties of a thermostable chitinase from Streptomyces thermoviolaceus OPC-520. AB - A chitinase was purified from the culture filtrate of Streptomyces thermoviolaceus OPC-520. The enzyme showed a high optimum temperature (70 to 80 degrees C), a high optimum pH level (8.0 to 10.0), and heat stability. This enzyme showed high sequence homology with chitinases from Serratia marcescens QMB1466 and Bacillus circulans WL-12. PMID- 8434930 TI - Cloning of the beta-amylase gene from Bacillus cereus and characteristics of the primary structure of the enzyme. AB - The gene encoding the beta-amylase of Bacillus cereus BQ10-S1 (SpoII) was cloned into Escherichia coli JM 109. A sequenced DNA fragment of 2,001 bp contains the beta-amylase gene. The N-terminal sequences (AVNGKG MNPDYKAYLMAPLKKI), the C terminal sequences (SHTSSW), and the amino acid sequences of the five regions in the beta-amylase molecules were determined. The mature beta-amylase contains 514 amino acid residues with a molecular mass of 57,885 Da. The amino acid sequence homology with those of known beta-amylases was 52.7% for Bacillus polymyxa, 52.0% for Bacillus circulans, 43.4% for Clostridium thermosulfurogenes, 31.8% for Arabidopsis thaliana, 31.5% for barley, 29.9% for sweet potato, and 28.9% for soybean. Ten well-conserved regions were found between the N terminus and the area around residue 430, but the C-terminal region of 90 residues has no similarity with those of the plant beta-amylases. The homology search revealed that this C-terminal region has homology with C-terminal regions of the beta amylase from C. thermosulfurogenes, some bacterial alpha-amylases, cyclodextrin glucanotransferase, and glucoamylase. Some of these sequences are known as the raw-starch-binding domain. These results suggest that B. cereus beta-amylase has an extra domain which has raw-starch-binding ability and that the domain has considerable sequence homology with those of other amylases or related enzymes from a wide variety of microorganisms. PMID- 8434931 TI - p-Coumaroyl and feruloyl arabinoxylans from plant cell walls as substrates for ruminal bacteria. AB - Growth of the ruminal bacteria Ruminococcus flavefaciens FD1, Selenomonas ruminantium HD4, and Butyrivibrio fibrisolvens 49 was limited by ester-linked feruloyl and p-coumaroyl groups. The limitation of growth on phenolic acid carbohydrate complexes varied with individual bacteria and appeared to be influenced by ability to hydrolyze carbohydrate linkages. PMID- 8434932 TI - The antimicrobial effect of a structural variant of subtilin against outgrowing Bacillus cereus T spores and vegetative cells occurs by different mechanisms. AB - Subtilin is a ribosomally synthesized antimicrobial peptide that contains several unusual amino acids as a result of posttranslational modifications. Site-directed mutagenesis was employed to construct a structural variant of subtilin in which the unusual dehydroalanine (Dha) residue at position 5 was changed to alanine. Proton nuclear magnetic resonance spectroscopy, amino acid composition, and N terminal sequence analysis established that the mutation did not disrupt posttranslational processing of the precursor peptide. This mutant subtilin was devoid of antimicrobial activity as assessed by its lack of inhibitory effects on outgrowth of Bacillus cereus T spores. However, this same mutant subtilin was fully active with respect to its ability to induce lysis of vegetative B. cereus T cells. Because an intact Dha-5 residue is required in the one instance but not in the other, it was concluded that the molecular mechanism by which subtilin inhibits (without lysis) spore outgrowth is not the same as the mechanism by which it inhibits (with lysis) vegetative cells. PMID- 8434933 TI - Growth and survival of Shigella flexneri in common Bangladeshi foods under various conditions of time and temperature. AB - Survival and growth of Shigella flexneri were assessed in various foods, including boiled rice, lentil soup, milk, cooked beef, cooked fish, mashed potato, mashed brinjal, and raw cucumber. Growth at 25 and 37 degrees C and survival at 5 degrees C were observed by viable counts on MacConkey agar. The organism grew well in all tested foods and growth increased from 10(5) to 10(8) to 10(10) cells per ml or g within 6 to 18 h after inoculation at 25 and 37 degrees C. PMID- 8434934 TI - Genus- and species-specific identification of mycoplasmas by 16S rRNA amplification. PMID- 8434935 TI - The pecking order of free radicals and antioxidants: lipid peroxidation, alpha tocopherol, and ascorbate. AB - Free radicals vary widely in their thermodynamic properties, ranging from very oxidizing to very reducing. These thermodynamic properties can be used to predict a pecking order, or hierarchy, for free radical reactions. Using one-electron reduction potentials, the predicted pecking order is in agreement with experimentally observed free radical electron (hydrogen atom) transfer reactions. These potentials are also in agreement with experimental data that suggest that vitamin E, the primary lipid soluble small molecule antioxidant, and vitamin C, the terminal water soluble small molecule antioxidant, cooperate to protect lipids and lipid structures against peroxidation. Although vitamin E is located in membranes and vitamin C is located in aqueous phases, vitamin C is able to recycle vitamin E; i.e., vitamin C repairs the tocopheroxyl (chromanoxyl) radical of vitamin E, thereby permitting vitamin E to function again as a free radical chain-breaking antioxidant. This review discusses: (i) the thermodynamics of free radical reactions that are of interest to the health sciences; (ii) the fundamental thermodynamic and kinetic properties that are associated with chain breaking antioxidants; (iii) the unique interfacial nature of the apparent reaction of the tocopherol free radical (vitamin E radical) and vitamin C; and (iv) presents a hierarchy, or pecking order, for free radical electron (hydrogen atom) transfer reactions. PMID- 8434936 TI - Purification and characterization of two exo-cellobiohydrolases from the brown rot fungus Coniophora puteana (Schum ex Fr) Karst. AB - Two extracellular exo-cellobiohydrolases (EC 3.2.1.91) were purified to homogeneity from the culture filtrate of the brown-rot fungus Coniophora puteana (Schum ex Fr) Karsten, strain EMPA 62. The purification scheme involved three successive chromatographic steps, namely Q Sepharose fast flow, Superose 12, and Fractogel TSK DEAE-650S. The two enzymes, named cellobiohydrolase (CBH) I and CBH II, were purified by a factor of 4.6 and 3.9, respectively, with an activity recovery of 9 and 19% of total, respectively. On sodium dodecyl sulfate polyacrylamide gel electrophoresis both enzymes migrated as single bands according to a M(r) of 52,000 for CBH I and 50,000 for CBH II; by FPLC gel filtration (TSK G3000 SW) the M(r)'s were higher (65,000 and 60,000). Both enzymes were glycosylated, had similar isoelectric points (pI 3.6 and 3.55) and nearly identical pH optima for activity close to 5. Endoglycosidase H digestion gave two distinct polypeptides where the molecular weight was lowered by 6.5 kDa for CBH I and by 2.5 kDa for CBH II. The specific activities for the hydrolysis of p-nitrophenyllactoside (pNPL) were nearly identical for both enzymes (0.46 versus 0.40 mumol mg-1 min-1 at 40 degrees C) and the Km values (6.8 and 4.3 mM at 30 degrees C) were also very close. Both enzymes were competitively inhibited by cellobiose: with pNPL as substrate, Ki values of 1.2 mM for CBH I and 2.4 mM for CBH II were determined. The two enzymes acted in an identical fashion on cellulose (either amorphous or crystalline) and on cellodextrins, liberating mainly cellobiose, but were inactive on dyed carboxymethylcellulose. Cellobiose was not hydrolyzed whereas cellotriitol was hydrolyzed to equimolar amounts of cellobiose and glucitol: these results support the interpretation that these enzymes are exo-cellobiohydrolases. Their presence in a brown-rot fungus is a new fact. PMID- 8434937 TI - Isolation and characterization of the cellobiose dehydrogenase from the brown-rot fungus Coniophora puteana (Schum ex Fr.) Karst. AB - The cellobiose dehydrogenase secreted by Coniophora puteana (Schum ex Fr) Karsten during growth on cellulose was isolated by successive anion-exchange chromatography on Q Sepharose fast flow and on TSK DEAE-650S and gel filtration on Superose 12. The enzyme was recovered at a 41% yield with a 43-fold increase in specific activity. The purified sample was homogeneous by polyacrylamide gel electrophoresis (PAGE), sodium lauryl sulfate (SDS)-PAGE, and electrophoretic titration curve analysis and stained positively for glycoprotein (periodic acid/Schiff base reaction) and hemoprotein (peroxidase reaction). By isoelectric focusing over a narrow pH range two distinct bands were observed: a major band (pI 3.9) flanked by a minor band on its acidic side. FPLC gel filtration on TSK G3000 SW revealed a M(r) of 192,000, whereas on SDS-PAGE a single band, corresponding to a M(r) of 111,000, was observed. The enzyme contained 13% sugar as mannose and upon digestion with endoglycosidase H, its molecular weight was lowered by 11 kDa. The enzyme showed a visible spectrum compatible with that of a b-type cytochrome containing a flavin cofactor. It was able to oxidize cellobiose, cellodextrins, and lactose at their C1-reducing group, with dichlorophenol indophenol as oxidant. Oxygen consumption (oxidase reaction in a Clark electrode) was not at a detectable rate. Km and Vmax for cellobiose oxidation were 84 microM and 2.98 mumol mg-1 min-1, respectively, but the enzyme was strongly substrate (cellobiose) inhibited (Kis 5.4 mM). PMID- 8434938 TI - The binding of terbium ions to tubulin induces ring formation. AB - The intrinsic fluorescence excitation and emission spectra of chicken brain tubulin showed the characteristic tryptophan fluorescence. The emission spectrum of Tb3+ in the presence of tubulin and GTP excited at 295 nm, showed four peaks, with the maxima at 490, 545, and 586 nm and a minor peak around 620 nm. Titration of tubulin with Tb3+ was followed by the increment in luminescence at 545 nm and showed a sigmoidal curve where the initial lag interval and the maximal luminescence intensity depended on tubulin concentration. The presence of Mg2+, Co2+, and Zn2+ diminished both the sigmoidicity of the curve and the maximal luminescence intensity. Titration of tubulin with Tb3+ also produced a sigmoidal increase in turbidity, which was shifted to the left with respect to the luminescence curve. The dependence of turbidity on the wavelength of the Tb(3+) induced polymers revealed that the large structures formed were not microtubules. Electron microscopy of the aggregates induced by Tb3+ showed mainly a lattice of double rings with side-by-side contacts. These results indicate that Tb3+ induces principally double ring formation and that these rings (33 +/- 2 nm external diameter) aggregate in large-ordered arrays. The luminescence of Tb3+ seems to be induced mainly by the aggregation of rings. PMID- 8434939 TI - Inhibition of porcine pancreatic elastase by 7-substituted 4-chloro-3 ethoxyisocoumarins: structural characteristics of modeled noncovalent complexes relate to the measured inhibition kinetics. AB - Kinetic measurements for the inhibition of porcine pancreatic elastase by 7 substituted 4-chloro-3-ethoxyisocoumarins were performed. To obtain possible explanations for the kinetic results, structures resulting from energy minimizations of inhibitor-enzyme complex structures where each inhibitor was initially positioned in 64 locations within the active site were obtained. In keeping with solution NMR studies, a positive-charged His-57 was employed. The number of low energy complex structures with Ser-195 O gamma-inhibitor benzoyl ester carbonyl carbon distances < or = 2.9 A, Ser-195 O gamma-inhibitor benzoyl ester carbonyl carbon-inhibitor benzoyl ester carbonyl oxygen angles > 91 degrees, and the inhibitor in the oxyanion hole exhibits a direct linear relationship to ln(Ki/k3). The proportion of those structures that show 7 substituent H-bonding between the inhibitor and porcine pancreatic elastase exhibits a direct relationship to k3. Assuming a direct linear relationship to ln(k3) and k3, finer differences in k3 than are experimentally observed are expected. The relationship with k3 and that with Ki/k3 are shown to be useful tools for the design of more potent 7-substituted 4-chloro-3-ethoxyisocoumarins. A novel inhibitor of this class (4-chloro-3-ethoxy-7-[(2-methyl-2- butylcarbamoyl)amino]isocoumarin) expected to be more potent is synthesized and tested. Its potency within experimental error is as predicted. Although the relationship observed with Ki/k3 involves only a twofold increase in Ki/k3 (a statistically significant increase), results with the novel inhibitor show the relationship to be valid over a four- to fivefold increase. PMID- 8434940 TI - Methionine toxicity in the rat in relation to hepatic accumulation of S adenosylmethionine: prevention by dietary stimulation of the hepatic transsulfuration pathway. AB - Rats were fed toxic levels of methionine with or without simultaneous dietary supplements of glycine and serine. Feed intake, growth rate, and metabolite concentrations in intestine, plasma, liver, skeletal muscle, and kidneys were monitored. Both toxic amounts of methionine and supplemental glycine and serine affected the tissue distribution of several amino acids resulting in similar, opposite, and diet-specific effects on the parameters studied. These changes were considered to be normal responses of amino acid metabolism to diet and to reflect metabolite flows between tissues. The feeding of toxic levels of methionine resulted in the accumulation of methionine, taurine, and glutathione in all tissues measured, but caused marked accumulation of S-adenosylmethionine and its catabolites only in liver. Hepatic accumulation of S-adenosylmethionine was accompanied by 40% stimulation of methionine adenosyltransferase and 40% repression of spermine synthase over a 2-week period. Simultaneous dietary supplements of glycine and serine combined with toxic levels of methionine markedly stimulated hepatic methionine catabolism. As a result, tissue distribution of methionine and glutathione returned close to normal in all tissues measured and accumulation of hepatic S-adenosylmethionine and its catabolites was prevented. Concentrations of taurine in liver, blood, and kidneys were further elevated, suggesting increased conversion of methionine to taurine followed by urinary excretion. These changes were accompanied by normalization of the above enzyme activities and the absence of symptoms of methionine toxicity. It was concluded that methionine toxicity is likely to be linked to hepatic accumulation of S-adenosylmethionine, resulting in liver dysfunction probably due to nonenzymatic methylation of liver macromolecules. Accumulation of tissue glutathione may also contribute to toxicity. PMID- 8434941 TI - Acquisition of ethanol tolerance in Saccharomyces cerevisiae: the key role of the mitochondrial superoxide dismutase. AB - Saccharomyces cerevisiae aBR10 cells are able to develop resistance to lethal ethanol concentrations (14%, v/v), by preexposure to a sublethal heat shock (37 degrees C) or ethanol stress (8%, v/v). Heat shock and 8% ethanol stress had no effect on the concentrations of glutathione [reduced (GSH) and oxidized (GSSG) forms] and on glutathione reductase and CuZn superoxide dismutase (SOD) activities, suggesting that the development of resistance to lethal ethanol concentrations is independent of these antioxidant defenses. In fact, a S. cerevisiae mutant, deficient in CuZnSOD, had an even higher ethanol tolerance, compared to the wild-type strain, and this mutation did not impair a further acquisition of ethanol tolerance. In contrast to CuZnSOD, the MnSOD activity seems to play a more important role in ethanol resistance. The MnSOD activity of the S. cerevisiae aBR10 cells increased upon exposure to heat shock or 8% ethanol. The higher tolerance to 14% ethanol in CuZnSOD deficient cells was also associated to a higher MnSOD activity, as compared to the aBR10 cells; this activity decreased during both stress pretreatments (while still higher than that observed in the wild-type strain). The results obtained suggest that maximum ethanol tolerance is attained with a MnSOD activity close to 1.0 U/mg protein. On either side of this value, the increased sensitivity of S. cerevisiae cells to 14% ethanol might be due to an inability to prevent either superoxide radical- or hydrogen peroxide-induced damages, respectively. These results are supported by the fact that a MnSOD deficiency renders yeast cells more ethanol sensitive. PMID- 8434942 TI - Inhibitory effect of spermine on ribosomal peptidyltransferase. AB - A cell-free system derived from Escherichia coli has been used to study the kinetics of inhibition of peptide bond formation by spermine at optimal Mg2+ concentration (10 mM). With the aid of the puromycin reaction, it was possible to show that spermine does not affect the final degree of peptide bond formation. However, spermine inhibits peptide bond formation at the kinetic phase of the reaction. A single molecule of spermine participates in the mechanism of inhibition. The type of inhibition of peptide bond formation by spermine is simple competitive, regardless of whether the ternary complex AcPhe-tRNA-poly(U) ribosome (complex C) is formed in the presence (Ki = 190 microM) or in the absence (Ki = 84 microM) of factors washable from ribosomes. Preincubation experiments of spermine with the individual components of complex C demonstrated that the inhibitory effect of spermine is closely related with its binding to AcPhe-tRNA. PMID- 8434943 TI - Analysis of biophysical differences between oxidized and reduced chloroplast NADP malate dehydrogenase. AB - Various properties of purified chloroplast NADP-malate dehydrogenase were analyzed with respect to the redox state of the light/dark-modulated enzyme. The reduced enzyme is less resistant to heat, but the instability can be overcome by the addition of the coenzyme NADPH. Similarly, instability of the reduced NADP MDH at high pH is alleviated by NADPH. The kinetics and protection characteristics of the alkylation of accessible thiols of NADP-MDH are used to describe the location of essential thiols relative to the active site, since again the coenzyme protects the active enzyme very effectively from inactivation by alkylation. The increased hydrophobicity of the reduced as opposed to the oxidized enzyme becomes apparent as the loss of activity from solutions due to adsorption to plastic surfaces. The kinetics and the solvent dependency of this process are analyzed and discussed, both from the practical (recovery of the purified enzyme) and the physiological point of view (in vivo protein/protein and protein/membrane interactions). The oxidized NADP-MDH has a lower tendency to bind to solid surfaces. NADP(H) efficiently prevents adsorption of the reduced form. Macromolecular solvents (polyethylene glycol), detergents (Triton X-100), or competing proteins also protect this otherwise very hydrophobic form from irreversible loss due to adsorption. Ribulosebisphosphate carboxylase/oxygenase and polyethylene glycol 10,000, however, used as competing substances only keep the oxidized, not the reduced, NADP-MDH in solution. PMID- 8434944 TI - Mitochondrial hexokinase in brain of various species: differences in sensitivity to solubilization by glucose 6-phosphate. AB - Approximately 90% of the hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) activity was solubilized by treatment of rat brain mitochondria with glucose 6-phosphate (Glc-6-P), while only about 20% of the hexokinase could be solubilized from human brain mitochondria. Intermediate amounts of solubilized activity were obtained with brain mitochondria from other species. In contrast, > or = 80% of the activity could be released by 0.5 M potassium thiocyanate (KSCN), regardless of the species from which the mitochondria were obtained. Hexokinase activities solubilized by treatment of bovine brain mitochondria with Glc-6-P (HKG6P) and by a subsequent treatment with KSCN (HKKSCN) were indistinguishable in their isoelectric focusing pattern and molecular weight, and both were inhibited by Glc-6-P with Ki approximately 20 microM. Both HKG6P and HKKSCN could bind to mitochondria from rat liver or brain, and both were again solubilized by a subsequent treatment with Glc-6-P. These results do not suggest any intrinsic molecular difference between HKG6P and HKKSCN. Rather, the difference in susceptibility to release by Glc-6-P is reasonably attributed to discrete types of binding sites for hexokinase on brain mitochondria, with the relative proportion of these varying with species. Bovine brain mitochondria bearing HKG6P and HKKSCN were not resolved by sucrose density gradient fractionation, suggesting that both forms may coexist on the same mitochondrion. Given the probable importance of mitochondrially bound hexokinase in regulating aerobic glycolysis in brain, these differences in hexokinase-mitochondrial interactions may be related to previously documented differences in cerebral energy metabolism of these various species. PMID- 8434945 TI - Protein and amino acid oxidation is associated with increased chemiluminescence. AB - Incubation of 4% bovine serum albumin (BSA) with 1 mM tert-butyl hydroperoxide (t BOOH) resulted in a peak of chemiluminescence followed by decay to a steady-state level of 18 counts per second above control. When using BSA of differing fatty acid content, the intensity of the initial peak was proportional to fatty acid content, while the steady-state chemiluminescence was independent of lipid content and depended only on BSA concentration. Light emission was inhibited by superoxide dismutase, desferrioxamine, and the antioxidant U-78518F. Oxidation of BSA by neutrophils activated with phorbol myristate acetate also increased chemiluminescence, in a process inhibitable by superoxide dismutase and U-78518F. When adding 1 mM t-BOOH in the presence of 20 microM heme to tryptophan, tyrosine, or to a lesser extent histidine, chemiluminescence correlated with increased oxygen consumption and the appearance of carbonyl derivatives, suggesting that chemiluminescence is a result of the decay to ground level of excited carbonyls. Lysine and glycine, on the other hand, were not oxidized to carbonyls after exposure to t-BOOH and did not emit light or consume significant oxygen during this challenge. PMID- 8434946 TI - Detection of NG,NG-dimethylarginine dimethylaminohydrolase in the nitric oxide generating systems of rats using monoclonal antibody. AB - In order to elucidate the biological role of NG,NG-dimethylarginine dimethylaminohydrolase (EC 3.5.3.18), we prepared monoclonal antibodies (mAbs) against the enzyme from rat kidney and examined the distribution of the enzyme in rats. Four mAbs have been obtained by the fusion of the spleen cells from BALB/c mouse immunized with the sodium dodecyl sulfate-denatured or native enzyme and P3X63Ag8U1 myeloma cells. All the mAbs were shown to bind to the denatured enzyme, but none of them could recognize the native enzyme. The occurrence of the enzyme protein in various rat tissues and cell systems such as peritoneal neutrophils and macrophages was examined using an immunoblotting technique with one of the mAbs. The immunoblotting analyses showed that the enzyme protein is widely distributed in rats, particularly, in kidney, pancreas, liver, brain, and aorta at high concentrations. Furthermore, the enzyme protein was clearly shown to exist in peritoneal neutrophils and macrophages. Since NG-monomethylarginine and NG,NG-dimethylarginine have been suggested to be specific blockers of the systems generating nitric oxide (NO), the above findings are of great interest in connection with the regulation of the NO production in such tissues and cell systems as aorta, brain, peritoneal neutrophils, and macrophages. PMID- 8434947 TI - Rabbit prostaglandin omega-hydroxylase (CYP4A4): gene structure and expression. AB - Genomic DNA containing the entire gene encoding P450 4A4, a cytochrome P450 that is elevated during pregnancy, was isolated on two overlapping recombinant phage. The isolated gene, CYP4A4, encodes a protein that differs at one amino acid position from the predicted sequence of a previously isolated cDNA. The intron/exon structure is highly conserved in relation to the clofibrate inducible genes CYP4A1, CYP4A2, and CYP4A6. However, the 5' flanking sequences of these genes exhibit little identity. Two transcriptional start sites of the CYP4A4 gene have been determined by RNase protection analysis and are located 37 and 40 nucleotides upstream of the initiation codon. Like other CYP4A genes the CYP4A4 promoter does not contain a TATA consensus sequence. CYP4A4 mRNAs are not detected in the lungs, liver, and kidneys of untreated rabbits by RNase protection assays. However, CYP4A4 mRNA is present to varying degrees in all three of these tissues during pregnancy with the greatest abundance observed in the lung and the lowest in the kidney. Treatment of male rabbits with dexamethasone also increases the levels of CYP4A4 mRNA in the lung and liver, but the levels are eightfold less than those seen for pregnant rabbits. Consensus recognition sequences for either the glucocorticoid or progesterone receptors were not found in 1086 bp of sequence upstream of the start of transcription. PMID- 8434948 TI - Fucosylated glycosphingolipids of human myeloid cells. AB - Our efforts to determine the carbohydrate binding specificity of two myeloid specific monoclonal antibodies (VIM-1 and VIM-10) resulted in the purification of three fucosylated glycosphingolipids from human chronic myelogenous leukemia cells. After repeated high-performance liquid chromatographic separations, two forms of fucosylated glycosphingolipids were resolved. VIM-1 and VIM-10 were found to bind to the heptaosylceramide Gal beta 1-4 (Fuc alpha 1-3)GlcNAc beta 1 3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1Cer with the Le(x) (Lewis X) epitope, but not to either the hexaosylceramide Fuc alpha 1-2Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1-Cer or the octaosylceramide Fuc alpha 1-2Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1Cer, each with the Le(y) (Lewis Y) epitope. The latter two glycosphingolipids are the first Le(y) antigens to be purified from human leukocytes and structurally characterized. Binding studies with a range of glycosphingolipids from myeloid cells and other biological sources demonstrated that VIM-1 and VIM-10 bind to Le(x) glycosphingolipids with five or more sugar residues, but not to a glycosphingolipid (III3Fuc-nLc6Cer) with an internal Le(x) trisaccharide. PMID- 8434949 TI - The effects of 21-aminosteroids on the redox status of iron in solution. AB - The effects of two 21-aminosteroids (U-74500A and U-74006F) on the oxidation and reduction of iron were investigated. U-74500A completely prevented ADP: Fe(II) autoxidation whereas U-74006F had only a slight inhibitory effect. The inhibition of Fe(II) oxidation by U-74500A was concentration dependent, with 100% inhibition occurring at concentrations equal to or greater than 25 microM in systems containing 50 microM Fe(II). When the Fe(II)-specific chelator Ferrozine was added to incubations containing U-74500A and ADP:Fe(II), formation of the Ferrozine:Fe(II) chromophore was slow, suggesting that U-74500A chelates Fe(II) with substantial affinity. Temporally, 20 min were required for complete formation of the Ferrozine-Fe(II) chromophore in the presence of U-74500A, whereas complexation in its absence was instantaneous. This phenomenon was not observed with U-74006F, Desferal, or ascorbate. In a system containing 25 microM ADP:Fe(II), U-74500A (25 microM) and U-74006F (25 microM) acted as iron reductants, reducing the iron at rates of approximately 2, and 0.1 microM/min, respectively. In addition, U-74500A fluorescence was quenched in a concentration dependent manner upon the addition of Fe(III), further demonstrating interactions between this compound and iron. The substructures of U-74500A consist of a steroid (U-76911) and a complex amine (U-82902E). When these compounds were assayed individually, it was found that U-82902E exhibited activities similar to those of U-74500A, whereas the free steroid had no effect. Studies employing cyclic voltammetry revealed that U-74500A had a relatively low oxidation potential (E = 228 mV), whereas U-74006F was much less susceptible to oxidation (E = 810 mV). Taken together, these data suggest that subtle effects on iron redox chemistry, which would in turn inhibit or eliminate the initiation of undesired oxidative reactions, may contribute to the potent antioxidant activities of U-74500A and U-74006F. PMID- 8434950 TI - Purification and characterization of cellobiose dehydrogenase, a novel extracellular hemoflavoenzyme from the white-rot fungus Phanerochaete chrysosporium. AB - Cellobiose dehydrogenase (CDH), an extracellular hemoflavoenzyme produced by the cellulose-degrading cultures of Phanerochaete chrysosporium, oxidizes cellobiose to cellobionolactone. CDH has been purified to homogeneity by a five-step purification procedure. The homogeneous CDH is monomeric and has a relative molecular mass of 90,000. It is also a glycoprotein with a neutral carbohydrate content of 9.4%. Purified CDH contains one heme b and one flavin adenine dinucleotide per monomer. Homogeneous CDH has a specific activity of 10.3 mumol min-1 mg-1 for cytochrome c reduction, in the presence of cellobiose. Cellotriose, cellotetraose, cellopentaose, and lactose also serve as substrates for CDH, in addition to cellobiose. Cytochrome c, dichlorophenol-indophenol, Mn3+, and benzoquinones can function as electron acceptors in these oxidations. Kinetic studies suggest that cellobiose is the preferred substrate and cytochrome c is the preferred electron acceptor. In the absence of these electron acceptors, oxygen serves as a poor electron acceptor and is reduced to H2O2. CDH is very stable in the pH range 3-10 and up to 50 degrees C. At lower pH or at higher temperature, CDH is inactivated due to the release of flavin from the active site. The native ferric form of the enzyme has absorption maxima at 420, 529, and 570 nm. With the addition of cellobiose, these absorptions shift to 428, 534, and 564 nm. The ferric enzyme does not bind azide or cyanide, implying that the heme iron is probably hexacoordinate. PMID- 8434951 TI - Photodynamic action of merocyanine 540 on leukemia cells: iron-stimulated lipid peroxidation and cell killing. AB - Merocyanine 540 (MC540) is a lipophilic photosensitizing dye of biomedical interest in connection with its ability to preferentially inactivate leukemia cells in bone marrow grafts and enveloped viruses in blood products. Evidence that iron plays a role in dye-mediated photokilling is presented in this report. When sensitized with MC540 and irradiated with visible light, cultured murine leukemia L1210 cells underwent lipid peroxidation (accumulation of iodometrically detectable lipid hydroperoxides) and photokilling (loss of clonogenic capacity). Selenium-deficient [Se(-)] cells, which expressed minimal selenoperoxidase activity, were found to be more sensitive to photoperoxidation and photokilling than selenium-replete [Se(+)] controls. Since redox active iron in the presence of electron donors has been shown to exacerbate photoperoxidative damage in isolated membrane systems, it was of interest to examine the possible role of iron in MC540/light-induced cytotoxicity. Involvement of iron was established by showing (i) that desferrioxamine (a high-affinity chelator and redox inhibitor of Fe3+) acted protectively on Se(-) and Se(+) cells and (ii) that treating these cells with sublethal concentrations of the lipophilic chelate ferric 8 hydroxyquinoline [Fe(HQ)2] made them much more sensitive to photokiling and thiobarbituric acid-detectable lipid peroxidation. Lehal damage induced by t butyl hydroperoxide was also amplified by Fe(HQ)2. Fe(HQ)2-enhanced photoperoxidation and photokilling were suppressed by alpha-tocopherol, suggesting that iron-catalyzed free radical reactions were involved. A mechanism based on iron-mediated one-electron reduction of nascent photoperoxides is proposed. We believe that under the conditions used, toxic one-electron chemistry overwhelms two-electron detoxification catalyzed by GSH-dependent selenoperoxidase(s). PMID- 8434952 TI - The structural requirements of sterols for membrane function in Saccharomyces cerevisiae. AB - Cultures of Saccharomyces cerevisiae strain GL7 auxotrophic for sterol were incubated with a series of sterols and sterol-like molecules (tetracyclic and pentacyclic triterpenoids) in order to determine the structural requirements of sterols for bulk membrane function. For growth support, the 3 beta-OH group could not be replaced by H, OMe, OBu, NH2, NHOH, OAc, keto, or 3 alpha-OH. A methyl group at C-14 was neither deleterious nor essential for activity. Removal of the C-4 geminal methyl group was obligatory for activity. Thus, no sterol-like triterpenoid supported growth (e.g., tetrahymanol, lanosterol, and cycloartenol). Growth support required a sterol with the longest methylene segment extending from C-20 not to exceed six contiguous C-atoms and the stereochemistry must be C 20 R. No significance could be attributed to branching at C-20 (i.e., to C-21), C 24 (when alkylated), or C-25 (regarding the isopropyl group). Double bonds in the nucleus were not essential for activity since cholestanol supported growth. In several incubations, the addition of trace levels of dietary ergosterol (0.5 microgram/ml) to the medium was necessary to promote growth and transformation of the bulk sterol to a membrane competent sterol(s). PMID- 8434953 TI - Quantitative in vitro assay for human immunodeficiency virus deoxyribonucleic acid integration. AB - An obligatory step of retroviral growth is the integration of a DNA copy of the viral RNA into the genomic DNA of the host. Recombinant human immunodeficiency virus type I (HIV-1) integrase (IN) expressed in Escherichia coli efficiently catalyzes the overall in vitro integration reaction, namely, the processing of the long terminal repeat (LTR) ends and the strand transfer reaction. Using the 3' end of synthetic oligonucleotides which match the termini of HIV-1 LTRs as substrate and supercoiled pSP65 DNA as the target, we describe an assay that is suitable for the enzymatic analysis of the integration and for testing candidate inhibitors of HIV IN protein. PMID- 8434954 TI - [Gene therapy]. AB - Recent progress of gene manipulation techniques enables us to insert foreign gene into human cells. This approach, so called gene therapy, is very attractive to treat molecular disease including congenital disorders or cancer. There have already been started 15 clinical protocols regarding gene therapy as well as gene marking mainly in U.S.A., In this reviewing article, we introduce the public opinion about the gene therapy in Japan comparing with that in western countries. We then introduce the current clinical protocols about gene therapy and gene marking. We also discuss the future prospects of gene therapy. The progress in this field may cast a new light on the treatment of congenital disorders as well as cancers. PMID- 8434955 TI - [Differentiation therapy of acute promyelocytic leukemia with all-trans retinoic acid]. AB - We treated 70 patients with acute promyelocytic leukemia (APL) with daily oral 45 mg/m2 all-trans retinoic acid (ATRA) in 2 multi-institutional prospective studies. Of 63 evaluable patients, 21 were resistant to initial induction chemotherapy, 10 were resistant to salvage chemotherapy after relapse, 17 were in the first relapse, 4 in the second relapse, 4 in the third relapse, and 7 were previously untreated. In the first study with ATRA from China, 18 (82%) of 22 evaluable patients achieved CR within 8 to 53 days with a median of 29 days. Initial peripheral leukemia cell counts were significantly less in the CR cases (p < 0.01). They were less than 100/cmm in 17 of 18 CR cases, and more than 200/cmm in all failure cases. Patients achieving CR received standard consolidation and maintenance chemotherapies, and the 16-month predicted continuing CR rate is 60%. Based on the first study, in the second study with ATRA from Hoffmann-La Roche AG, if initial peripheral leukemia cell counts were more than 200/cmm, chemotherapy was first given and then ATRA was started. Of 41 evaluable patients, 36 (88%) achieved CR within 11 to 91 days with a median of 34 days. Of 3 patients who received preceding chemotherapy due to high leukemia cell counts, 2 achieved CR. Morphological evidence of differentiation was noted in all CR cases, with Auer rods in mature segmented neutrophils in 13 cases. The clinical signs of DIC decreased rapidly within a few days and disappeared in CR cases. Toxicities attributable to ATRA were minimal and included cheilitis, xerosis, dermatitis, gastrointestinal disorders, bone pain, liver damage and high serum triglyceridemia. PMID- 8434956 TI - [Chemotherapy and bone marrow transplantation for acute leukemia]. AB - Chemotherapy (CT) and bone marrow transplantation (BMT) have made remarkable progress in recent years. The comparison of both treatment modalities has become an important issue. The methods of comparison, however, should be varied according to the subjects and purposes of comparison. For a general comparison of both CT and BMT, the registry data of both treatments, seems adequate. For the comparison of a CT regimen with a BMT regimen, a randomized control study seems most adequate. in order to get an overview. For the selection of treatment for a certain patient, comparison of CT and BMT data from the center in which the patient will be treated seems most important. As the latter comparison we have studied the rate of early death, the rate of long-term survival and medical costs in leukemia patients diagnosed and followed for 5 years, at the Center for Adult Diseases Osaka. The early death rate was similar in both groups of patients. The long-term survival rate was 78% in BMT and 28% in CT patients. Cost effectiveness was also favorable in BMT patients. Data on CT and BMT in each center should be prepared for the selection of treatment for patients at each center. PMID- 8434957 TI - [Interferon therapy for chronic myelogenous leukemia]. AB - Interferon alpha (IFN alpha) has been used in the treatment of chronic myelogenous leukemia (CML). The initial trial was made in 1983 by Talpaz et al. Their first report suggested that IFN alpha treatment could achieve high hematological remission. The cause of the effect was unclear, but may be mediated through interaction cell surface membrane and inhibitory protein production. IFN alpha was related to some T cell immunity, and could be taken to be Ph1 positive cell inhibition by normal T cell. Although IFN alpha therapy has limited use with get Ph1 negative hematopoiesis, intensive treatment of this kind is needed to minimize Ph1 clone, using various therapy combination with IFN alpha. PMID- 8434958 TI - [Bestatin therapy of chronic myelogenous leukemia]. AB - We proposed a new approach to treat chronic myelogenous leukemia using a combination of busulfan and Bestatin. Twenty-three patients with Ph1 positive CML including 20 in the chronic phase and 3 in the accelerated phase, were treated with the combination therapy. Complete hematologic remission was obtained in all patients. Complete cytogenetic response (CCR) was obtained in 6 patients (26%), partial cytogenetic response (PCR) in 1 (4%), and minor cytogenetic response (MCR) in 6 (26%). In particular, of 13 patients in early chronic phase, 5 (39%) achieved CCR, 1 PCR, 3 MCR. Complete suppression of Ph1+clone was further confirmed by molecular analysis. Cytogenetic conversion to a normal diploid state persisted for 6-41+ months (median 22 months+). Three year survival rate was 86.6 +/- 9.0% (95% confidence limit). Furthermore, the long-term complete hematologic remission in the accelerated phase patients without progression of the disease may be indicative of a long-term survival. We conclude that Bestatin effectively controls CML and allows reappearance of diploid hemopoietic cells in some patients. The rationale for this combination therapy is that busulfan suppresses the proliferation of leukemic progenitors and decreases tumor burden to the level where Bestatin exhibits its antiproliferative effects. Bestatin is not merely antiproliferative but provides more complex biological properties capable of enhancing repopulation of normal residual stem cells. PMID- 8434959 TI - [Antitumor activity of BOF-A2, a new 5-fluorouracil derivative, against human cancers xenografted in nude mice by intermittent administration]. AB - Antitumor effects of BOF-A2 given intermittently was evaluated with human gastric (H-111, H-83), colorectal (H-110, H-143) and lung (H-74, LC-376) cancers xenografted in nude mice and compared with those by continuous administration. BOF-A2 was orally given 3 or 4 times per week at 30 or 35 mg/kg over 4 weeks. This drug was effective to 5 strains except H-110 (IR > or = 58%), remarkably effective to H-81 and H-143 (IR > or = 80%) and caused tumor regression in mice bearing H-81 especially. Moreover, the drug was effective to H-74 which is rather insensitive to 5-FU and its known derivatives. When the drug was given orally to nude mice xenografted LC-376, 5-FU levels in the tumor tissue was notably durative for a long time as compared to UFT. It would be concluded that BOF-A2 was much effective to insensitive tumor to fluorinated pyrimidines or other anticancer, because of persistence of high levels of 5-FU in the tumor tissue. On the other hand, diarrhea which is caused by other fluorinated pyrimidines or consecutive administration of BOF-A2, was mild by the intermittent administration of BOF-A2. PMID- 8434960 TI - [Subrenal capsule assay of nude mice for testing the effectiveness of UFT for rat prostatic carcinoma (R3327)]. AB - Combination effect of UFT and CDDP against the rat prostatic carcinoma (R3327) was evaluated by the subrenal capsule assay in nude mice. The tumor growth of R3327 was inhibited in proportion to the UFT concentration. Anticancer effect of UFT was elevated by co-administration of CDDP. These data suggest a clinical usefulness of UFT administration with CDDP for hormonally refractory advanced prostatic carcinoma. PMID- 8434961 TI - [Experimental study on the combined treatment of UFT with etoposide against mouse Lewis lung carcinoma]. AB - Synergistic cytotoxicity between FUra and etoposide was determined in Lewis lung carcinoma (3LL) cells by clonogenic assay. With the same exposure condition, chasing the time course of DNA strand breaks and repair by DNA unwinding assay. DNA repair in the exposure sequence of etoposide prior to FUra was remarkably delayed more than that by etoposide alone. There was a little overlap in normal tissue toxicity of UFT and etoposide since 65% of the full dosages of the two agents can be used in combination and main toxicities (suppression of body weight, decrease in WBC and damage of intestinal mucosa) were dispersed with dependence on the schedule of administration. Moreover, this combined treatment with the most tolerated dose resulted in the highest survival effect on 3LL bearing mice than each agent alone. These data suggest that combination chemotherapy of UFT with etoposide show high antitumor activity and low host toxicity, and will be clinically useful. PMID- 8434962 TI - [Phase I clinical study of TT-62. Research group of TT-62]. AB - TT-62 is a new derivative of FdUMP, which is the active metabolite of 5-FU. A phase I clinical study of TT-62 was conducted by a cooperative study. The same patients received single and 2-week oral administration of TT-62. Starting from 60 mg/m2 (1n), the dose was escalated to 420 mg/m2 (7n). In the single administration, the maximum tolerated dose (MTD) could not be determined. In the 2-week administration, MTD was 420 mg/m2, and the dose limiting factor was gastro intestinal disturbances such as anorexia, nausea, vomiting and diarrhea. Increases in GOT.GPT and a decrease in hemoglobin content were observed. After administration was stopped all side effects disappeared. TT-62 was detected mainly in the plasma, while trace amounts of 5-FU and FUdR were also detected. TT 62 was excreted mostly in the urine, as alpha-fluoro-beta-alanine (FBAL). The cumulative urinary excretion of FBAL was about 80% of the total dose, and the oral absorption of TT-62 was thus thought to be good. PMID- 8434963 TI - [Clinical evaluation of NK 622 (toremifene citrate) in advanced or recurrent breast cancer--a comparative study by a double blind method with tamoxifen]. AB - Efficacy and safety of NK 622 (toremifene citrate) were compared with tamoxifen (TAM) by a double blind test in patients with advanced or recurrent breast cancer. NK 622 and TAM were given orally for 12 weeks or more at daily doses of 40 and 20 mg/body, respectively. Eligible cases in NK622 and TAM groups were both 57 patients. No significant difference was observed in patient characteristics between either group. Response rates were 26.3% (8 CR and 7 PR, 15/57) in the NK 622 group and 28.1% (3 CR and 13 PR, 16/57) in the TAM group. Median values of duration to onset of CR were 91 days in the NK 622 group and 169 days in the TAM group. The duration was significantly shorter with the NK 622 group. Median duration of efficacy in CR and PR cases was 155 days in the NK 622 group and 154.5 days in the TAM group. Adverse effects were encountered in 7 patients (12.3%) of each of the 2 groups. The side effects were fatigue, hot flush, WBC decrease, abnormal values in liver function tests, etc. in the NK 622 group and anorexia, nausea, eruption, feeling of warmth, sweating, dry mouth, dizziness, abnormal values in liver function tests, etc. in the TAM group. Administration was discontinued in one patient with eruption and another patient with abnormal values of liver function tests in the TAM group, while there was no such case in the NK 622 group. Including the discontinued cases, the side effects were moderate and reversible in both groups. The patients in whom a drug was determined as useful or more numbered 24/57 (42.1%) in the NK 622 group and 23/57 (40.4%) in the TAM group. There was not significant difference between the 2 groups in the above results except the duration to onset of CR. From these results, NK 622 is expected to show comparable efficacy, safety, and usefulness in patients undergoing TAM treatment for advanced or recurrent breast cancer. PMID- 8434964 TI - [Alternative combination chemotherapy with mitomycin C, vincristine, methotrexate, 5-fluorouracil, cis-platinum and adriamycin for adenocarcinoma of the lung]. AB - Efficacy of an alternative combination chemotherapy with MMC, VCR, MTX, 5-FU, CDDP and ADM for adenocarcinoma of the lung is reported. Forty-one advanced cases (stage III: 9; IV: 32) were chosen for the chemotherapy. Two combination chemotherapies MMC + VCR + MTX + 5-FU + CDDP: MVMFP; MMC + VCR + MTX + 5-FU + ADM: MVMFA were repeated alternatively for 8 consecutive weeks with 2 interposed rest weeks, and this regimen was completed in 34 cases. All 41 cases were evaluable. Three and 26 cases achieved complete and partial responses, respectively. The response rate was 70.7%, and the median survival time was 13 months. The adverse effects of the chemotherapy observed were tolerable: alopecia (63.4%), gastrointestinal symptoms (14.5%), bone marrow toxicity (12.2%) and liver dysfunction (4.8%). These results indicate that our MVMFP/MVMFA alternative chemotherapy is quite effective for adenocarcinoma of the lung, comparable or superior to conventional chemotherapies. PMID- 8434965 TI - [Increase in CDDP therapeutic index by lower concentration and longer infusion time--home chemotherapy for ovarian cancer]. AB - Twenty-two patients with ovarian cancer stage III and IV received combination chemotherapy with CDDP, adriamycin (ADM) and cyclophosphamide (CPM), and were studied for response and side-effects. Patients were divided into two groups according to the following CDDP infusion schedules. (CAP 1) CDDP 7mg/sqm/8 hrs/saline 500 ml/d1-d10, ADM 35 mg/sqm/d1, CPM 350 mg/sqm/d1: 8 cases; (CAP 2) CDDP 70 mg/sqm/2 hrs/d1, ADM 35 mg/sqm/d1, CPM 350 mg/sqm/d1: 14 cases. The overall response rate (CR + PR) was 62.5% in CAP 1, and 50% in CAP 2 (on statistical difference: NS). The 3-year survival rate was 54.7% in CAP 1 and 38.5% in CAP 2 (NS). Side effects of nausea, vomiting and nephrotoxicities were remarkably reduced in CAP 1. These data suggest that lower concentration and longer infusion time of CDDP administration increases the therapeutic index. This infusion schedule is suitable for chemotherapy at home or on an outpatient clinic basis, especially in patients with ovarian cancer. PMID- 8434966 TI - [Preclinical and clinical studies on a tumor marker, galactosyltransferase associated with tumor (GAT), in ovarian cancer (first report)--preclinical study of GAT assay kit and clinical study of normal level]. AB - We conducted preclinical and clinical studies on GAT: Galactosyltransferase Associated with Tumor, a newly developed tumor marker of ovarian carcinoma. This paper presents the results of evaluation of a GAT assay kit, the normal range of its values, and analysis of its value relative to age, menstrual cycle, and stage of pregnancy. Calibration curve, reproducibility, analytical recovery test, and dilution test all yielded favorable results, and the assay system was proved to be reliable in both precision and reproducibility. However, special attention must be paid to highly hemolytic samples because of a positive error in GAT value for samples with a high concentration of hemoglobin. The cut-off value was set at 16U/ml based on the mean+2SD of healthy females. A uniform cut-off value could be employed since neither age nor stage of menstrual cycle had any observable influence on the level. The positive rate for healthy subjects was 3.1%, when the cut-off value of 16 U/ml was used. On the other hand, elevation of the GAT value was observed during the progression of pregnancy. PMID- 8434967 TI - [Preclinical and clinical studies on a tumor marker, galactosyltransferase associated with tumor (GAT), in ovarian cancer (second report)--clinical significance of GAT and comparison with other tumor markers]. AB - Galactosyltransferase Associated with Tumor (GAT) was clinically studied in cases of ovarian cancer. When two cut-off levels of GAT were compared, the cut-off level of 16 U/ml (which corresponds to mean + 2SD among healthy females) was found to be more suitable than the cut-off level of 14 U/ml (the level maximizing the diagnostic efficiency between malignant and benign ovarian tumors). When the GAT positive rate was examined for gynecologic tumors, the rate was 5.7% for benign ovarian cyst, 6.6% for endometriosis, 20.5% for cervical cancer, 19.5% for endometrial cancer, and 52.9% for ovarian cancer. The GAT positive rate for different histologic types of ovarian carcinoma was relatively high for each type, e.g., 55.0% for clear cell adenocarcinoma and 66.7% for endometrioid adenocarcinoma. The GAT positive rate increased gradually with the stage of ovarian cancer. In patients with benign diseases, in particular endometriosis, the GAT positive rate was lower than the positive rate with any other simultaneously determined marker (CA602, CA125, CA54/61, CA72-4, STN, and SLX). The GAT level most weakly correlated with the level of any of the other markers assessed. An assay combining GAT with CA602 or CA54/61 resulted in a higher positive rate and a higher diagnostic efficiency, when compared with the assay for GAT alone. The lower positive rate of GAT in endometriosis, when compared with the positive rate of other markers, suggests the usefulness of GAT in distinguishing malignant ovarian tumors from benign ovarian tumors. The use of GAT in a combination assay is expected to overcome the disadvantages of CA602 or CA125. PMID- 8434968 TI - [5-fluorouracil + low-dose leucovorin and cisplatin sequential chemotherapy with dipyridamole for advanced nonresectable squamous cell carcinoma of the lung: a case report]. AB - A 62-year-old man diagnosed as Stage IIIB advanced non-resectable squamous cell carcinoma of the lung was treated with a sequential combination of 5-fluorouracil (5-FU) and cisplatin (CDDP), with concurrent administration of leucovorin and dipyridamole as a biochemical modulator for 5-FU. After 3 cycles, the mass reduced in size more than 70% in CT scan and the patient underwent a thoracotomy. Histologically, the primary lesion was completely necrotized and of the 10 metastatic regional lymph nodes, only one lymph node contained a small amount of viable cells and 3 additional cycles were conducted. The patient is still alive 30 months after initial chemotherapy. This regimen appears to be potentially useful for non-small-cell lung cancer and warrants further clinical study. PMID- 8434969 TI - [A case of liver metastasis from retroperitoneal leiomyosarcoma successfully treated by intra-arterial infusion chemotherapy of adriamycin or epirubicin using an implantable reservoir]. AB - A 59-year-old woman was diagnosed as having liver metastasis (H3) 38 months after undergoing resection for retroperitoneal leiomyosarcoma. A catheter was placed in the hepatic artery and intra-arterial infusion chemotherapy using an implantable reservoir was performed with 30 mg of adriamycin or epirubicin at each treatment every 2-4 weeks. Imaging revealed that the tumor had been markedly reduced, and a partial response was obtained for 18 months. The patient has survived for 33 months since liver metastasis was detected. Although effective chemotherapy for metastatic leiomyosarcoma in the liver has been poorly documented, intra-arterial infusion chemotherapy proved highly effective in this case, suggesting that it effectively improved the prognosis. PMID- 8434970 TI - [A case of breast cancer with multiple organ metastases in which single low dose administration of 5'-DFUR proved effective]. AB - A 58-year-old woman with multiple organ metastases from breast cancer who had undergone radical mastectomy three years ago, was treated with oral 5'-DFUR 600 mg/day. Complete remission (CR) of lymph node metastasis has been maintained for twenty-two weeks, with partial response (PR) against skin, liver and pleural metastases from 94 weeks of treatment. The patient, who continues to be treated, is well and enjoying a favorable quality of life. 5'-DFUR is considered to be an effective first choice for treating a patient with advanced or recurrent breast cancer. PMID- 8434971 TI - [Effect of preoperative FPL (5-fluorouracil, cisplatin, leucovorin) therapy on patients with primary unresectable advanced gastric cancer]. PMID- 8434972 TI - The combined use of immediate intraoperative tissue expansion and meshing technique. PMID- 8434973 TI - Clinical diagnosis of pigmented lesions using digital epiluminescence microscopy. Grading protocol and atlas. AB - BACKGROUND AND DESIGN: Epiluminescence microscopy (ELM) is a clinical technique that permits in vivo visual inspection of pigmented anatomic structures of the epidermis, dermoepidermal junction, and papillary dermis. A protocol is proposed for systematic visual inspection of pigmented lesions. Seventy pigmented lesions were imaged with a digital ELM camera system. Images were visually inspected for eight "global" ELM features, 23 "local" ELM features, and 18 network features. An atlas of the most clinically significant ELM features is presented with pilot estimates of their sensitivity and specificity for detecting melanoma. RESULTS: Preliminary data suggest that ELM features that may be most specific for melanoma include multicomponent pattern, nodular pattern, pseudopods, radial streaming, blue-gray areas, whitish veil (milky way), and sharp network margins. Epiluminescence microscopic features that may be most sensitive for melanoma include pigment dots, peripheral erythema, peripheral dark network patches, marked mean network irregularity, network line thickness variability, radial streaming, blue-gray areas, and whitish veil (milky way). Epiluminescence microscopic features that may be most sensitive for severe melanocyte atypia include pigment dots, peripheral erythema, hypopigmented network patches, peripheral dark network patches, marked mean network irregularity, and focal absence of network. In addition, features that may have a very high specificity for benign lesions include saccular pattern (suggests hemangioma), globular pattern (suggests a compound or dermal nevus), and multiple comedolike openings (suggests seborrheic keratosis). CONCLUSIONS: Features most sensitive for severe atypia and melanoma could form the basis for a screening test for considering biopsy. Features most specific for melanoma then could be applied to further triage management of pigmented lesions that meet initial screening criteria. In addition, features with very high specificity for benign lesions may help develop ELM criteria to avoid unnecessary surgery. PMID- 8434974 TI - Rashes in immunocompromised cancer patients. The diagnostic yield of skin biopsy and its effects on therapy. AB - BACKGROUND AND DESIGN: Rashes in immunocompromised cancer patients can be important, and skin biopsies are often recommended for their evaluation. The objectives of this study were to determine how often skin biopsy in these patients is performed and how often it alters diagnosis and therapy. Records of all immunocompromised adults with cancer and acute rash seen by dermatology consultants on a hematology-oncology ward of a university hospital for 39 months were reviewed to determine patients' course and outcome (190 episodes of rash in 123 patients). RESULTS: Skin biopsies were performed on 108 rashes (57%); 82 rashes (43%) were evaluated without biopsy. Among the 108 patients who underwent a biopsy of their rashes, the biopsy findings supported the prebiopsy diagnosis in 51% (95% confidence interval [CI], 42% to 60%), altered it in 44% (95% CI, 35% to 53%), and did not contribute to the final diagnosis in 6% (95% CI, 2% to 12%). Fifteen of 108 biopsies (14%) (95% CI, 7% to 21%) changed systemic therapy. Most treatment changes were for cutaneous reactions to drugs; biopsy never resulted in the diagnosis of untreated systemic infection. Biopsy findings that altered diagnoses were not more likely to change therapy. Among the 82 rashes in which biopsies were not performed, review of the chart revealed no adverse sequelae (0%) (95% CI, 0% to 5%), which would have made a biopsy advisable. CONCLUSIONS: Skin biopsy findings often changed dermatologic diagnoses in immunocompromised cancer patients, but treatment changes based on biopsy results were much less common, and altered diagnoses in patients who underwent biopsy often did not change therapy. Untreated systemic infection was never diagnosed by means of a skin biopsy. Skin biopsies of these rashes may not be mandatory for either diagnostic or therapeutic reasons. PMID- 8434975 TI - Anatomical differences of port-wine stains in response to treatment with the pulsed dye laser. AB - BACKGROUND AND DESIGN: Anecdotal reports and clinical observations have suggested that the response of port-wine stains to treatment with the pulsed dye laser is variable and dependent on the anatomical location of the lesion. To investigate anatomical variation in response to treatment, a retrospective study of 259 adults and children with port-wine stains of the head and neck treated with the pulsed dye laser was undertaken. Evaluation was performed by comparing simultaneously projected pretreatment and completion-treatment photographs. Anatomical differences in response were evaluated in three ways: (1) by anatomical subdivision of the head and neck into regions, (2) by dermatomal distribution, and (3) by response for midline lesions. The head and neck was subdivided into eight anatomical regions, which were independently evaluated for response. In addition, response for individual dermatomes and for midline lesions was evaluated. Response in all cases was assessed by determining the percentage of lightening from 0% to 100% (where 100% represents complete response) at the completion of treatment. Response grades were also assigned, using grades poor (0% to 25% lightening), fair (26% to 50% lightening), good (51% to 75% lightening), or excellent (76% to 100% lightening). RESULTS: One hundred thirty seven adults and 122 children were included in the study. Evaluation by subdivision of the head and neck into regions revealed that in adults and children the centrofacial regions (medial aspect of the cheek, upper cutaneous lip, and nose) responded less favorably than the other grouped regions (periorbital, forehead/temple, lateral aspect of the cheek, neck, and chin); the centrofacial regions showed a good response (mean lightening, 70.7%) while the other grouped regions of the head and neck showed an excellent response (mean lightening, 82.3%). Evaluation by dermatomal distribution revealed that dermatome V2 showed a good response (mean lightening of 73.8%), while combined dermatomes V1, V3, and C2/C3 showed an excellent response (mean lightening of 82.4%). Evaluation of midline lesions revealed excellent responses in adults and children (mean lightening, 92.4%). CONCLUSIONS: Port-wine stains of the head and neck in adults and children demonstrate differences in response to treatment with the pulsed dye laser according to their anatomical location. Centrofacial lesions and lesions involving dermatome V2 in adults and children respond less favorably than lesions located elsewhere on the head and neck. Midline lesions respond very favorably in adults and children. PMID- 8434976 TI - Demonstration of interleukin 8 and autoantibodies to interleukin 8 in the serum of patients with systemic sclerosis and related disorders. AB - BACKGROUND AND DESIGN: Interleukin 8 (IL-8), a chemotactic cytokine produced by various cell types, displays structural homology to the connective tissue activating peptide III. Little is known of the possible role of IL-8 in connective tissue disorders. We therefore determined serum concentrations of IL-8 and autoantibodies to IL-8 in 134 patients with systemic sclerosis (SSc) and related connective tissue disorders, as well as in pooled serum from 28 healthy control subjects by a sensitive enzyme-linked immunosorbent assay. RESULTS: Interleukin 8 was undetectable in the pooled serum from 28 healthy controls, but detectable in serum samples from 24 of the 134 patients described above. It was detected in 13 of 60 patients with limited SSc and in eight of 48 patients with diffuse SSc. It was also detectable in one of three patients with eosinophilic fasciitis and in two of 10 patients with Raynaud's syndrome without skin involvement. In contrast, none of the three patients with morphea or the 10 patients with eosinophilia-myalgia syndrome had detectable IL-8 levels. We further determined the concentration of autoantibodies to IL-8 in the same serum samples. The values in healthy controls were 6.7 +/- 0.2 ng/mL (mean +/- SEM). Significantly elevated autoantibody levels were detected in patients with limited SSc (21.5 +/- 1.7), diffuse SSc (23.4 +/- 2.2), and Raynaud's syndrome (20.5 +/- 3.7). Elevated levels were also detected in patients with eosinophilic fasciitis (43.7 +/- 8.6) and morphea (14.7 +/- 3.2). Normal levels (7.5 +/- 2.0) were found in patients with eosinophilia-myalgia syndrome. Analysis of variance between the levels of autoantibodies to IL-8 and duration of the disease, extent of skin involvement, drug therapy, or serologic findings failed to show a significant correlation. CONCLUSIONS: These results suggest that increased production of IL-8 may relate to activation of mononuclear phagocytes, fibroblasts, or endothelial cells, among other cell types, in patients with SSc, but not in those with eosinophilia-myalgia syndrome. This activation could be related to the production of autoantibodies to IL-8. PMID- 8434977 TI - Magnetic resonance imaging in the evaluation of lymphangioma circumscriptum. AB - BACKGROUND: Lymphangioma circumscriptum is characterized clinically by grouped vesicles, some of which may be filled with serosanguineous fluid. The depth and extent of involvement of lymphangioma circumscriptum cannot be adequately estimated from the cutaneous examination. OBSERVATION: We describe two patients with lymphangioma circumscriptum evaluated by magnetic resonance imaging. Magnetic resonance imaging accurately demonstrated the true extent of involvement. CONCLUSIONS: With magnetic resonance imaging to delineate the entire lesion of lymphangioma circumscriptum, one can (1) provide education to the family regarding the extent of involvement and (2) prevent incomplete invasive surgical procedures from being performed. PMID- 8434978 TI - Five cases of coexistent primary ocular and cutaneous melanoma. AB - BACKGROUND: Patients with the atypical mole syndrome are prone to cutaneous melanoma, but their risk of ocular melanoma has not been established. We studied the skin of 207 consecutive patients with eye melanoma referred to Moorfields Hospital in London, England, in an attempt to determine what percentage of these patients had the atypical mole syndrome phenotype. OBSERVATIONS: Five patients were seen who had primary melanomas of both the eye and the skin. In three of these patients, the cutaneous melanomas were discovered only as a result of this study. The number of cutaneous melanomas expected in this cohort of patients with eye melanomas was no more than 0.4 on the basis of the United Kingdom incidence of both tumors. This difference was highly significant. CONCLUSIONS: The occurrence of primary cutaneous melanoma in five patients from a cohort of 207 patients with eye melanoma (or the premalignant melanocytic lesion of the conjunctiva called "primary acquired melanosis") provides strong evidence of an association between cutaneous and ocular melanoma. Three of the five patients also had the atypical mole syndrome phenotype, suggesting that the atypical mole syndrome predisposes to both types of melanoma. PMID- 8434979 TI - Psammomatous melanotic schwannoma. A new cutaneous marker for Carney's complex. AB - BACKGROUND: Noncutaneous psammomatous melanotic schwannoma has recently been reported as an unusual component of Carney's complex (myxomas, spotty pigmentation, and endocrinopathy). The most common locations for this lesion include peripheral nerve roots and the gastrointestinal tract. OBSERVATIONS: A cutaneous psammomatous melanotic schwannoma is reported in a patient with known Carney's complex. This neoplasm was pseudoencapsulated, with epithelioid to spindle-shaped cells and no nuclear atypia. Immunostaining was positive for S100 protein and vimentin, as well for HMB-45 antibody. Electron microscopy showed melanosomes in cytoplasmic processes of cells that were ensheathed by layers of reduplicated basal lamina. CONCLUSIONS: Location in the superficial soft tissues is extremely unusual for psammomatous melanotic schwannomas. Recognition of this new cutaneous marker as a part of this complex may aid in identification of individuals at risk for cardiac myxomas. It is also important that this lesion is not mistaken for melanoma, given the strong HMB-45 positivity. PMID- 8434980 TI - The turmoil of Europe. What can dermatologists do? PMID- 8434981 TI - Magnetic resonance in dermatology. PMID- 8434982 TI - Magnetic resonance imaging. Its role in the neuroradiologic evaluation of neurofibromatosis, tuberous sclerosis, and Sturge-Weber syndrome. AB - BACKGROUND: Magnetic resonance imaging (MRI) has rapidly become a major diagnostic technique, displacing computed tomography (CT) as the primary neuroimaging modality in many disorders of the central nervous system. Neuroimaging studies are valuable in the diagnosis and management of neurofibromatosis, tuberous sclerosis, and Sturge-Weber syndrome. This article reviews the technique of MRI and its role in identifying the characteristic central nervous system manifestations of these neurocutaneous syndromes. OBSERVATIONS: MRI offers superior soft-tissue contrast without the use of ionizing radiation. It provides more detailed imaging than CT of the characteristic central nervous system lesions of neurofibromatosis, tuberous sclerosis, and Sturge-Weber syndrome. In neurofibromatosis type 1, these include optic glioma, astrocytoma, and plexiform neurofibroma, and "unidentified bright objects" that are seen only with MRI. Bilateral acoustic neuromas are the hallmark of neurofibromatosis type 2. Subependymal nodules and cortical and white matter tubers are characteristic of tuberous sclerosis. Manifestations of Sturge Weber syndrome include leptomeningeal angiomatosis, hemiatrophy, cortical calcification, and patchy parenchymal gliosis and demyelination. CONCLUSIONS: MRI, especially with gadolinium enhancement, appears to be more sensitive than CT in the detection of neurofibromatosis, tuberous sclerosis, and Sturge-Weber syndrome. MRI may be the imaging method of choice for following certain patients or screening family members. PMID- 8434983 TI - A blistering eruption in an elderly woman. Linear IgA dermatosis (LAD). PMID- 8434984 TI - A papulovesicular eruption in a man receiving chemotherapy for metastatic melanoma. Squamous syringometaplasia (squamous metaplasia) of the eccrine glands. PMID- 8434985 TI - Persistent plaque on the shoulder of a Chinese woman. BCG granuloma. PMID- 8434986 TI - Epidermal hyperplasia with or without atypia in patients exposed to mustard gas. PMID- 8434987 TI - Zinc and essential fatty acid therapy for necrolytic migratory erythema. PMID- 8434988 TI - Quantitative evaluation of muscle weakness in scleroderma patients using magnetic resonance imaging and spectroscopy. PMID- 8434989 TI - Pachydermodactyly: a case of an unusual type of reactive digital fibromatosis. PMID- 8434990 TI - Kaposi's sarcoma in kidney transplant recipients. PMID- 8434991 TI - PECAM-1 (CD31) is expressed on proliferating endothelial cells, stromal spindle shaped cells, and dermal dendrocytes in Kaposi's sarcoma. PMID- 8434992 TI - A new autosomal recessive anomaly mimicking Fanconi's anaemia phenotype. AB - A family in which three siblings born to related parents all manifested clinical abnormalities characteristic of Fanconi's anaemia (microcephaly, short stature, slow growth, beak nose, micrognathia, skin dyspigmentation and forearm and thumb dysplasia in 2/3) is reported. All five family members had normal spontaneous chromosome breakage, a normal response to diepoxybutane and mitomycin C, and were fully informative for linkage with four DNA markers from chromosome 20q12-13.3 with no evidence for linkage. It is concluded that abnormalities typical for Fanconi's anaemia are inherited as an autosomal recessive without the defect responsible for increased chromosomal fragility and independently from the genes so far identified as being responsible for Fanconi's anaemia. PMID- 8434993 TI - Psychosocial adjustment of adult survivors of a paediatric dialysis and transplant programme. AB - The social adjustment of 45 young adult renal patients who commenced treatment for end stage renal disease (ESRD) as children and of 48 age and sex matched controls were compared. Renal patients were less socially mature than controls. More lived with their parents, fewer had an intimate relationship outside the family, they had fewer school qualifications, and there was more unemployment among them. The majority, however, were in employment and the level of subjective stress and support derived from most of these areas was comparable in renal patients and in controls. Having a close relationship with a member of the opposite sex was the only domain in which renal patients reported more stress than controls. Early start of illness and current health problems were associated with poorer social outcome. A lifelong history of ESRD leads to suboptimal or delayed social functioning on conventional indicators. However this does not lead to increased overall distress in the patients about their social circumstances and quality of life does not appear to be substantially impaired. PMID- 8434994 TI - Cerebral blood flow velocity monitoring in pyogenic meningitis. AB - Transcranial Doppler ultrasound monitoring of cerebral blood flow velocity (CBFV) was performed on 17 children (age range 8 days to 6 years) with pyogenic meningitis. Serial measurements of the peak systolic, end diastolic, mean flow velocity, and resistance index (equal to peak systolic velocity minus end diastolic velocity divided by peak systolic velocity) were obtained over the period of their hospital admission. In all 16 survivors there was a significant decrease in the final resistance index compared with the initial resistance index due to a significant increase in the end diastolic velocity. There was a significant increase in the final mean flow velocity. In four patients the decrease in intracranial pressure and increase in cerebral perfusion pressure after mannitol infusions was accompanied by a corresponding decrease in resistance index and increase in mean flow velocity. A pressure passive CBFV response with a significant linear correlation for resistance index/mean arterial pressure may suggest a loss of cerebrovascular autoregulation. These results suggest that in the early phase increased cerebrovascular resistance may contribute to a relative impairment of cerebral perfusion. Non-invasive monitoring by transcranial Doppler ultrasound may be helpful for early detection of deterioration in cerebral haemodynamic trends. PMID- 8434995 TI - Cystic fibrosis in Asians. AB - The clinical course of cystic fibrosis in nine Pakistani Asians was compared with 18 non-Asian age and sex matched controls. The Asian patients grew Pseudomonas aeruginosa at an earlier age (4.0 v 7.5 years), tended to have lower respiratory function test results (forced vital capacity 58.5 v 76.8% predicted; forced expiratory volume in one second 79.8 v 100.3% predicted), and had significantly greater concentrations of immunoglobulin IgG (13.4 v 10.1 g/l). They had a lower weight for age (78.4 v 95.7%) and weight for height (90 v 98.5%) despite similar intakes of dietary energy. Four of the nine Asians carried the delta F508 mutation compared with 17 of 18 controls. All the Asian patients were born in the UK; seven of their mothers were born in Pakistan and had moderate or severe difficulties with the English language. It is concluded that Asian patients may have a more severe clinical course than matched controls and that genetic and environmental factors may be contributory. PMID- 8434996 TI - Biofeedback training in chronic constipation. AB - Twenty nine patients, aged 5-16 years, were studied to evaluate whether biofeedback training is effective in treating children with chronic constipation and encopresis; the clinical outcome at six weeks and 12 months was also evaluated. Patients received on average five biofeedback training sessions. The existence of external anal contraction or decreased rectal sensation in 16 (55%) and eight (27%) of the children, respectively was identified on manometry. After biofeedback training, 26 (90%) of the patients learned to relax the external anal sphincter; 18 (63%) normalised rectal sensation. The training resulted in a significant increase in defecation frequency and a significant decrease in encopresis. At six weeks, 16 (55%) of the patients were clinically symptom free. At follow up after 12 months the results were sustained. Only three patients showed a relapse within six months, of whom two were successfully treated with one extra training session. Biofeedback training might be a useful therapeutical approach in children with chronic constipation and encopresis. PMID- 8434997 TI - Low injury rates in elite athletes. AB - A group of 453 elite young athletes (231 boys, 222 girls) in five two year age groups from 8-16 years of age was followed up for two years in order to identify self reported injuries over that period. Four sports were studied, namely football (soccer), gymnastics, tennis, and swimming. The injury rate was low with just over half the children suffering one or more injuries per year, with the majority of those injured sustaining one injury only. Over the two year period of intensive sporting activity this amounted to less than one injury per 1000 hours of training. The highest risk of injuries was in football (67%) and the lowest in swimming (37%). Most injuries (70%) were acute and of a minor nature, although overuse injuries did require longer periods off training and competition than acute injuries (20 v 13 days). Footballers appeared to sustain more significant injuries than other sports as judged by the time required to resume training and/or competition (16 days after acute and 57 after overuse). No significant associations were found between injury rate, injury severity, sex, and pubertal status with the single exception of female gymnasts in whom more injuries occurred in the latter stages of puberty. Only four of the 453 athletes reported injury as a reason for retiring from their chosen sports. Most injuries in elite young athletes are minor, their prevalence is low and, at least in the short to medium term, do not constitute a significant health problem. PMID- 8434998 TI - Children of HIV positive haemophilic men. AB - All 14 children who were conceived at the time their 12 haemophilic fathers were anti-HIV positive were shown to be HIV negative and to be healthy physically and mentally. Eleven of the 12 female partners have remained anti-HIV negative and one has seroconverted. Despite counselling it is likely that children will continue to be conceived by anti-HIV positive haemophiliacs. PMID- 8434999 TI - Resolution of pancreatic ascites with octreotide. AB - A 7 month old infant with pancreatitis and ascites was managed successfully with subcutaneous octreotide and external drainage of a pseudocyst. An endoscopic retrograde cholangiopancreatographic examination showed no congenital abnormality and was consistent with chronic pancreatitis. Octreotide has a possible therapeutic role in pancreatic ascites. PMID- 8435000 TI - Fructose breath hydrogen tests. AB - Fructose absorption was studied by the breath hydrogen test in 114 healthy children aged 0.1-6 years, given either 2 g/kg or 1 g/kg of fructose. All 57 children given 2 g/kg had peak breath hydrogen excretions > or = 20 ppm. At 1 g/kg only 25/57 (44%) showed incomplete absorption and the percentage incompletely absorbing fructose and the peak breath hydrogen value were significantly higher in children aged 1-3 years. Interestingly, this age distribution correlates with that of toddler diarrhoea. PMID- 8435001 TI - Transient protein S deficiency with deep venous thrombosis during Salmonella typhimurium infection. AB - A patient with deep venous thrombosis and low protein S activity during the course of Salmonella typhimurium infection is presented. Although protein S deficiency has been reported in patients with disseminated intravascular coagulation, it was not present in this patient and his protein S activity was normal after the findings of infection and deep venous thrombosis disappeared. PMID- 8435002 TI - The growing pains of community child health. PMID- 8435003 TI - Allowances for care for children with cystic fibrosis. PMID- 8435004 TI - Poland. PMID- 8435005 TI - Pancreatic enzyme supplementation in cystic fibrosis. PMID- 8435006 TI - The value of proximal small intestinal biopsy in the differential diagnosis of chronic diarrhoea. PMID- 8435007 TI - Positive hepatitis serologies with treatment for Kawasaki syndrome. PMID- 8435008 TI - 'Well baby' review and screening for hepatobiliary diseases. PMID- 8435009 TI - Optimum method for growth hormone treatment. PMID- 8435010 TI - Optimum method for growth hormone treatment. PMID- 8435011 TI - Paediatric medical manpower. PMID- 8435012 TI - The new disability living allowance. PMID- 8435013 TI - A survey of basic resuscitation knowledge among resident paediatricians. AB - A telephone questionnaire was undertaken to evaluate the knowledge of resident paediatricians on the subject of the basic resuscitation of the acutely sick child. The questionnaire was targeted at 88 resident paediatricians in hospitals accepting paediatric emergencies in four health regions. Outcome was measured as a correct response to questions based on several emergency scenarios and on the confidence expressed of basic resuscitation knowledge. The subject of emergency management of the child with a compromised upper airway was poorly answered with 40/73 (55%) resident paediatricians suggesting an incorrect endotracheal tube size for an 8 year old child. Fluid management was also deemed unsatisfactory with only 36/73 (49%) providing adequate transfusion secondary to haemorrhagic shock. In addition only 19/73 (26%) mentioned the intraosseous route as a means of obtaining vascular access in a child in extremis. Confidence of the knowledge of basic resuscitation of children was low among resident paediatricians with only 30/73 (41%) expressing confidence and 69/73 (94%) expressing a desire for more formal training in paediatric resuscitation. Resident paediatricians are usually the key personnel in the management of very sick children. This survey demonstrates a low level of basic resuscitation knowledge among resident paediatricians of all grades that must be remedied at a local and national level. PMID- 8435014 TI - Exclusion criteria and outcome in pressure reduction of intussusception. AB - Experience of 53 episodes of intussusception was examined to compare the observed success rate of pressure reduction with potential outcome had stricter exclusion criteria been applied (history > 24 hours, presence of rectal bleeding, radiological signs of intestinal obstruction). With stricter criteria 25 avoidable laparotomies would have been performed. Most infants can be cured of intussusception by pressure reduction and though some must be excluded this decision should be based on clinical assessment by those experienced in its management. Pressure reduction should not be attempted in the absence of a surgeon with regular experience of intussusception. PMID- 8435015 TI - Objective confirmation of crying durations in infants referred for excessive crying. AB - Parents commonly seek clinicians' help for infant crying that they judge to be excessive. To date there is no independent evidence whether such babies actually cry more than average. To assess this, maternal diary and 24 hour audiotape recordings of the crying periods of 16 infants referred for excessive crying were compared with equivalent measures of a normative sample. The overall amounts of crying measured by the two methods were similar. The referred infants cried substantially more over 24 hours and in the afternoon and evening. The difference approached significance in the morning but was insignificant at night time. Some qualifications to the findings are indicated. PMID- 8435016 TI - Prevention of viral induced asthma attacks using inhaled budesonide. AB - Thirty two preschool children were entered into a double blind, placebo controlled study using intermittent budesonide to treat viral induced wheeze. Active treatment was either 800 micrograms twice a day via a spacer or 1600 micrograms twice a day via a spacer and facemask in those children too young to use a mouthpiece. Treatment was started at the onset of an upper respiratory tract infection and continued for seven days or until symptoms had resolved for 24 hours. Each child remained in the study until they had completed using one pair of budesonide and placebo inhalers in random order without the need for additional oral prednisolone. Twenty five children completed 28 treatment pairs. All 25 families were asked to express a preference after completing their first treatment pair: 12 preferred budesonide and six preferred placebo; seven had no preference. Symptom scores were compared in 17 treatment pairs that were completed without the need for oral prednisolone. Mean day and night time wheeze in the first week after infection were significantly lower in those receiving budesonide. Intermittent inhalation of budesonide can modify the severity of wheezing in preschool children developing asthma after viral respiratory infections but improvements were modest with the doses used in this study. PMID- 8435018 TI - Compliance with growth hormone treatment--are they getting it? AB - A study was undertaken to investigate compliance in patients receiving growth hormone treatment. Two hundred patients completed a questionnaire designed to establish understanding about and compliance with treatment; 50% of our patients failed to comply with all aspects of their treatment. Failure to respond to treatment seems to be associated with poor compliance. PMID- 8435017 TI - Secondary thrombocytosis. AB - To estimate the incidence and causes of secondary thrombocytosis in children, a 12 month study of all patients attending a children's hospital and discovered to have a platelet count over two times the upper normal limit (> 800 x 10(9)/l) was undertaken. Data so obtained were analysed both separately and together with those from two previous studies to gain as broad a perspective as possible. Of 7916 children who had platelet counts during the study period, 36 (0.5%) produced a value > 800 x 10(9)/l; there were 19 boys and 17 girls. There was a preponderance of young infants (median age 13 months). Twenty seven of the 36 had some sort of associated infection, bacterial in 18 and viral in nine. The other nine were either recovering from anti-neoplastic chemotherapy (n = 6), were post operative (n = 2), or simply iron deficient (n = 1). Combining these patients with those described in previous studies allowed a review of 139 unselected children with very high platelet counts. Fifty three (38%) had infections, 29 (20%) had traumatic or surgical tissue damage, 16 (11%) had malignant disease undergoing chemotherapy or surgery, and 13 (9%) had connective tissue or autoimmune disorders. Secondary thrombocytosis is not rare and is most frequently seen in very young infants after infection. It can arise in a wide variety of other circumstances including rebound from myelosuppression, iron lack, or as part of an acute phase response. It is clinically unimportant in terms of morbidity and requires no treatment other than that for the primary condition. PMID- 8435019 TI - Extracorporeal life support in paediatrics. AB - Extracorporeal membrane oxygenation (ECMO) is a life support technique based on modifications of heart-lung bypass technology. It is used to support severe but potentially reversible pulmonary or cardiopulmonary failure. There is increasing use of the technique for neonates and a return of interest in its use for adults. The number of non-neonatal paediatric patients receiving pulmonary support with ECMO worldwide is, however, small, and survival rates average less than 50%. Initial experience in 15 patients aged 3 months to 5 years with a high survival and low morbidity is reported. PMID- 8435020 TI - Pulmonary veno-occlusive disease: diagnosis during life in four patients. AB - Pulmonary veno-occlusive disease is a rare form of primary pulmonary hypertension of unknown aetiology. Four cases were diagnosed in young patients. The diagnosis was suspected on the basis of clinical, radiological, echocardiographic, and catheter evidence and confirmed by taking a lung biopsy sample. In all patients the histology showed obstruction of the pulmonary veins by intimal fibrosis. The clinical course of all patients has been one of progressive deterioration. Although there is no specific treatment for this disease, to establish the diagnosis during life is of great importance in overall clinical management, including counselling the patient and family. PMID- 8435021 TI - Does cigarette smoking lead to the subsequent development of leukemia? PMID- 8435022 TI - Futility and its wider implications. A concept in need of further examination. PMID- 8435023 TI - Futility in practice. PMID- 8435024 TI - Vasodilator therapy for congestive heart failure. Lessons from mortality trials. AB - Congestive heart failure is a major clinical and public health problem affecting between 2 and 3 million people in the United States. Whereas myocardial dysfunction assumes a central pathophysiologic role in the development of chronic heart failure, alterations in the peripheral vasculature and neurohormonal systems serve to modulate the heart failure state. Short-term studies of nonspecific vasodilators and angiotensin-converting enzyme inhibitors demonstrate a beneficial effect of these agents on left ventricular function, hemodynamics, exercise tolerance, and quality of life in patients with congestive heart failure and depressed left ventricular systolic function. More recently, several large scale multicenter trials have documented improved survival in patients with heart failure who received vasodilating agents. These studies, in conjunction with hemodynamic and functional studies, argue strongly for the widespread use of vasodilator therapy, notably the angiotensin-converting enzyme inhibitors, for congestive heart failure and left ventricular systolic dysfunction. PMID- 8435025 TI - Conflicting aims. Voluntary health insurance and contemporary medical practice. AB - American medicine is financed today by a patchwork of systems formed around a concept of competitive voluntary health insurance that evolved over the past 50 years. This article reviews the theory of health insurance from a clinical perspective to examine whether changes in medical science and practice have made such an insurance system obsolete. As it is currently applied, a system of competitive voluntary health insurance conflicts with the goals of modern medical practice due to advances in screening and in treatment and the need to deal more effectively with paying for care of unknown efficacy. Proposals to reform health insurance must deal with the medical failings of competitive voluntary health insurance and should do more than simply extend the current system to cover more Americans. PMID- 8435026 TI - Cigarette smoking and adult leukemia. A meta-analysis. AB - BACKGROUND: Increasing evidence suggests that certain forms of adult leukemia may be related to cigarette smoking. METHODS: To evaluate the association between cigarette smoking and adult leukemia, we conducted a meta-analysis of available studies. Data were identified through an English-language MEDLINE search for the period 1970 through 1992 and through our knowledge of ongoing and unpublished studies. Among the studies identified, the meta-analysis included seven prospective studies and eight case-control studies. The US Surgeon General's criteria were used to assess the evidence for causality. RESULTS: A positive association between smoking and certain histologic types of leukemia was found in both prospective and case-control studies. The summary smoking-related risk derived from prospective studies (relative risk, 1.3; 95% confidence interval, 1.3 to 1.4) was greater than that based on case-control data (relative risk, 1.1; 95% confidence interval, 1.0 to 1.2). Prospective data suggested an elevated risk of myeloid leukemia associated with cigarette smoking (relative risk, 1.4; 95% confidence interval, 1.2 to 1.6). Pooled case-control data showed increased smoking-associated risk for acute nonlymphocytic leukemia (relative risk, 1.3; 95% confidence interval, 1.1 to 1.5). Risk of leukemia increased according to the number of cigarettes smoked per day. Population-attributable risk calculations suggested that approximately 14% of all US leukemia cases (including 17% of myeloid and 14% of acute nonlymphocytic leukemias) may be due to cigarette smoking. CONCLUSIONS: The consistency, temporality, and biologic plausibility of this relationship augment our findings, which support a causal relationship between cigarette smoking and certain forms of adult leukemia. Further studies are needed to examine risk among women, dose-response effects, and variation in risk by histologic type. PMID- 8435027 TI - A meta-analysis of the effects of nonsteroidal anti-inflammatory drugs on blood pressure. AB - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have well-known gastrointestinal and renal toxic reactions. Effects of NSAIDs on blood pressure are less appreciated. A meta-analysis was performed to determine the hypertensive effects of NSAIDs and rank them by magnitude of change in mean arterial pressure (MAP). METHODS: A literature search of published English-language studies of NSAIDs and their effects on blood pressure was done. Studies were included if they met the following criteria: (1) the studies were intervention studies; (2) NSAIDs at any dose or aspirin at doses of 1.5 g/d or greater were included; (3) documentation of blood pressure was provided; and (4) the studies were 24 hours in duration. Studies were excluded if 20% or more of their participants dropped out or if the dose of antihypertensive drugs was adjusted while the subjects were taking NSAIDs. The major outcome was change in MAP while patients were receiving NSAIDs. Each NSAID arm was extracted from its trial. Information on possible confounders, including subject age, trial quality, amount of dietary salt intake, and whether study subjects were hypertensive or normotensive, was recorded. We calculated the average change in MAP on each NSAID, adjusting for confounders. RESULTS: Fifty-four studies with 123 NSAID treatment arms met inclusion criteria. The mean age of subjects was 46 years. Of the 1324 participants, 1213 subjects (92%) were hypertensive. The effects of NSAIDs on blood pressure were found solely in hypertensive subjects. Among these, the increase in MAP after adjusting for amount of dietary salt intake was 3.59 mm Hg for indomethacin (57 treatment arms), 374 mm Hg for naproxen (four arms), and 0.49 mm Hg for piroxicam (four arms). The MAP decreased by 2.59 mm Hg for placebo (10 arms), 0.83 mm Hg for ibuprofen (six arms), 1.76 mm Hg for aspirin (four arms), and 0.16 mm Hg for sulindac (23 arms). The effects on MAP by using placebo, sulindac, and aspirin were statistically significantly different from indomethacin. CONCLUSIONS: In short-term use, NSAIDs vary considerably in their effect on blood pressure. Of the drugs studied, indomethacin and naproxen were associated with the largest increases in blood pressure. The average effects of piroxicam, aspirin, ibuprofen, and sulindac were negligible. PMID- 8435028 TI - Mycoplasma pneumoniae pneumonia requiring hospitalization, with emphasis on infection in the elderly. AB - PURPOSE: To determine the frequency and the clinical characteristics of Mycoplasma pneumoniae pneumonia in the elderly. METHODS: Analysis of cases of M pneumoniae pneumonia accumulated as part of a prospective study of community acquired pneumonia. RESULTS: Sixty-four (4.9%) of 1300 patients had pneumonia due to M pneumoniae. Six (9.3%) of the 64 were 65 years of age or older. None of the elderly patients had a discharge diagnosis of M pneumoniae compared with 21 of those 64 years of age or younger (36%). Sixty-four percent of the patients with M pneumoniae received erythromycin therapy compared with 45% of 1118 of the patients with community-acquired pneumonia. The clinical features of the six elderly patients with M pneumoniae did not allow distinction from other causes of pneumonia. One patient presented with normal pressure pulmonary edema due to infection with both M pneumoniae and respiratory syncytial virus; a second patient had his Salmonella carrier state converted to bacteremia during his episode of M pneumoniae. Three presented as nonspecific pneumonia in the elderly, while one patient had a slowly resolving infection due to a narrowed bronchus. The 58 patients who were 64 years of age or younger demonstrated four previously unrecognized or underemphasized features of M pneumoniae infection--prolonged thrombocytopenia, one patient; recurrent pulmonary hemorrhage, one patient; thrombocytosis, 45% of the patients; and prolonged hospital stay, eight (13.7%) of the 58 patients. Only one patient died (1.5%) and this was a result of Shy Drager syndrome. CONCLUSIONS: Mycoplasma pneumoniae accounts for 4.9% of community-acquired pneumonia requiring hospitalization, and 9% of these patients were 65 years of age or older. There are no clinical features that distinguish this form of pneumonia from that due to other agents. The mortality rate from this infection is low even in the elderly. PMID- 8435029 TI - Mycobacterium tuberculosis bacteremia in patients with and without human immunodeficiency virus infection. AB - PURPOSE: To determine the incidence of Mycobacterium tuberculosis bacteremia in a general hospital and to describe the clinical characteristics, therapy, and outcome of patients with bacteremic tuberculosis. PATIENTS AND METHODS: Clinical charts of all patients in whom M tuberculosis was isolated from blood cultures during a 5-year period were reviewed. Mycobacterium tuberculosis was detected by means of a nonradiometric blood culture system. RESULTS: Of 285 patients with culture-proved tuberculosis in whom blood cultures were obtained, 50 (14%) had M tuberculosis bacteremia. Of 42 patients analyzed, 34 (81%) were infected with human immunodeficiency virus (HIV) and eight (19%) were not infected with HIV. Blood was the only or the first positive specimen in 14 patients (33%). Most HIV infected patients (79%) were intravenous drug users, and 40 (88%) had clinical and/or radiologic evidence of involvement of one or more organs. Lungs were affected in 71% of the patients. In-hospital mortality was 18% in HIV-infected patients with mycobacteremia. Among eight non-HIV-infected patients, four had an underlying disease, and none was immunosuppressed. Disseminated disease was diagnosed in three patients. Two patients died as a consequence of tuberculosis in this group. CONCLUSIONS: Mycobacterium tuberculosis bacteremia is common in HIV-infected patients and is possible in nonimmunosuppressed subjects. Blood cultures are helpful in making the diagnosis of tuberculosis and can help establish a diagnosis of disseminated infection. PMID- 8435030 TI - Carotid plaque associations among hypertensive patients. AB - OBJECTIVE: To assess the relationship between cardiovascular risk factors and carotid plaque. DESIGN: Hypertensive patients were screened for randomization into the Multicenter Isradipine Diuretic Atherosclerosis Study, a trial intended to determine if blood pressure control by isradipine as compared with hydrochlorothiazide will blunt the progression of carotid plaque (intima plus media thickness, 1.3 to 3.5 mm) in patients with serum cholesterol levels of less than 6.85 mmol/L (265 mg/dL) without insulin-dependent diabetes mellitus or estrogen therapy. Demographics of those who underwent B-mode ultrasound evaluations at common, bifurcation, and internal carotid artery sites to detect plaque were assessed from a southern and a northern site. SETTING: Participants were from ambulatory outpatient clinics associated with medical schools. PATIENTS: The initial screening included 1823 hypertensive volunteer patients who were between 40 and 83 years of age who had a diastolic pressure of 90 to 114 mm Hg (or < 90 mm Hg with treatment). OUTCOME MEASURES: Complete data were collected on the variables of age, cholesterol, cigarette smoking, race, gender, and the presence of carotid plaque in 1126 patients. RESULTS: All variables were significantly associated with carotid plaque (intima plus media thickness, > or = 1.3 mm). The adjusted percentage with plaque was 66.4% +/- 3.4% for blacks and 70.1% +/- 2.3% for whites at the southern site and 42.7% +/- 4.5% for blacks and 61.3% +/- 3.2% for whites at the northern site. The rate of plaque was 75.8% among cigarette smokers, despite a mildly elevated cholesterol level. CONCLUSIONS: Although these 1126 cases do not constitute a random sample of patients, these data suggest that there may be regional differences in racial tendencies toward plaque among blacks. PMID- 8435031 TI - Salmonella aortitis. A report of a successfully treated case with a comprehensive review of the literature. AB - A successfully treated case of Salmonella infection of the thoracic aorta is described. Salmonella enteritidis was isolated from blood cultures and from operative cultures of the aorta. Computed tomography suggested the site of infection, and the resection of the thoracic aortic aneurysm with specific antibiotic therapy resulted in a satisfactory outcome. Although once invariably fatal, improved diagnostic roentgenographic techniques, more potent antibiotics, and surgical advances have resulted in at least 45 reported survivors over the last 15 years. The pathogenesis, clinical and laboratory characteristics, and the treatment of aortitis due to Salmonella species are reviewed in 98 cases reported in the English-language literature since 1948. Early diagnosis and a combination of prompt surgical intervention and antibiotic therapy are essential for survival. PMID- 8435032 TI - Living organ donation is still ethically acceptable. PMID- 8435033 TI - Medical futility decision. PMID- 8435034 TI - In vitro activity of thalidomide against Mycobacterium avium complex. PMID- 8435035 TI - Sexual functioning of male anabolic steroid abusers. AB - The effects of anabolic steroid use on male sexual behavior were assessed using a structured clinical interview administered to male body builders currently using steroids, and to two comparison groups (body builders with a past but not current history of steroid use, and a group of "natural" body builders who had never used steroids). Current anabolic steroid users had a significantly higher coital and orgasmic frequency than did comparison athletes. They also reported a significantly higher incidence of erectile difficulties during the past month. Beliefs concerning the sexually stimulating effects of steroids did not correlate with the frequencies of specific sexual behaviors. The data support the contention that anabolic steroids, as androgenic compounds, enhance sexual desire. PMID- 8435036 TI - Gender identity disorder and courtship disorder. AB - A hypothetical connection between gender identity disorder and courtship disorder was investigated in 274 heterosexual male patients of the following types: nontransvestic fetishists for female attire; transvestic fetishists; patients with gender identity disorder of adolescence and adulthood, nontranssexual type; and transsexuals. Of these patients, 53 had also demonstrated one or more of the putative expressions of courtship disorder. The proportion each of these types contributed to this group of 53 patients with a courtship disorder was compared with the same type's proportional contribution to the group of 221 gender identity patients without a courtship disorder. The transvestic fetishists contributed a significantly larger percentage and the transsexuals a significantly smaller percentage of individuals to the group with a courtship disorder than to that without a courtship disorder. Theoretical implications of this asymmetry are discussed. PMID- 8435037 TI - Physical attractiveness of boys with gender identity disorder. AB - University students blind to group status rated boys with gender identity disorder and clinical control boys regarding their physical attractiveness. Ratings were made of the face and upper torso from photographs taken at the time of clinical assessment (mean age, 8.1 years). On all five adjectives (attractive, beautiful, cute, handsome, and pretty), boys with gender identity disorder were judged to be more attractive than were the clinical control boys. Attractiveness correlated with extent of behavioral femininity in the clinical control group, but not in the group of boys with gender identity disorder. The extent to which the group differences in attractiveness were due to objective, structural differences in facial attractiveness vs. socially created, or subjective, processes is discussed. PMID- 8435038 TI - Homosexual and bisexual identity in sex-reassigned female-to-male transsexuals. AB - Descriptions of female-to-male transsexuals who are sexually attracted to men are rare. This is a report on nine of them. Their awareness of gender dysphoria preceded their awareness of their attraction to men. Their wish to undergo sex reassignment as a means of resolving their gender dysphoria superseded any concerns about their sexual orientation or sexual adaptation after surgery. Several had had sexual relationships with men before sex reassignment which were unsatisfactory because these men viewed our subjects as women. After sex reassignment, the subjects successfully established sexual relationships with gay men; in some of them even penovaginal intercourse was part of their sexual activities. While hormonally and surgically reassigned, none of our subjects had had phalloplasty. All nine subjects were interviewed and given psychological tests measuring sexual satisfaction and psychological adjustment. Their results were compared to those of a group of self-identified gay men. No major differences in sexual satisfaction and psychological adaptation were found. The phenomenon of female-to-male transsexuals who develop a sexual orientation toward men may be more common than previously thought. Regarding female gender dysphoric individuals, our findings challenge the issue of using sexual orientation in classification systems of gender dysphoria syndromes and as a risk factor in the decision regarding sex reassignment. Further, our study invites us to rethink the genital criterion in the assessment of sexual orientation. PMID- 8435039 TI - Frequency of sexual problems and sexual dysfunction in middle-aged Danish men. AB - The frequency of sexual dysfunction of a representative group of Danish middle aged men was recorded, using a questionnaire and an interview that contained, respectively, 12 and 23 questions about sexual problems. The study sample consisted of 439 51-year-old men, all of whom received the questionnaire. Of these men, 100 were also interviewed. Interviewed men more frequently reported erectile dysfunction and previous contact with a therapist due to sexual problems at interview than in the questionnaire. Thus, 16 men (4% of the study population) who reported erectile dysfunction in the questionnaire constituted only a fraction of the true number. At interview nearly 40% of the men reported some kind of sexual dysfunction. There were, however, only 7% who found their problems abnormal for their age--and only 5% of the interviewed men intended to seek treatment for their problems. PMID- 8435040 TI - China: acceptability and effect of three kinds of sexual publication. AB - A nationwide political movement named "sweeping away the yellow subjects" ("yellow" means erotic and pornographic as does "blue" in U.S.) was launched by the Communist Party and then enlarged by the government in China since the end of July 1989. Almost all of the written, audio, and visual publications were banned as long as they described any kind of sexual behavior. Publishers were punished by arrest. At least 20 persons were put to death for selling "the yellow subjects." The argument of the Party and the government for launching such a movement was that the yellow subjects result in readers and viewers becoming sexual offenders. Although we are unable to test directly with enough survey data, we studied two basic facts: (i) How many and what kind of persons accepted three kinds of publications on sexuality: scientific books, erotic literature, and visual materials? (ii) What kind of and how much influence was there on the readers' and viewers' attitudes towards other subjects which were not directly sexual? As the first research on this subject in China, we conducted a social survey with a questionnaire. What we found provided a basis for confirming one aspect of the hypothesis that a sex revolution appeared in China in 1988. PMID- 8435042 TI - Distinct levels of relationships between tospovirus isolates. AB - The taxonomic relations of a number of tospovirus isolates, collected in different geographical areas and from different host plants, were studied. To delineate these isolates, properties such as susceptibility of a limited range of host plants, symptomatology, cytopathology, nucleocapsid composition, serology of their nucleocapsid proteins, and nucleotide sequence homology were compared. The results show that isolates which have previously been discriminated as members of three different serogroups, should in fact be regarded as representatives of at least three distinct virus species in the tospovirus genus. PMID- 8435041 TI - Human T-cell leukemia virus type 1 protease protein expressed in Escherichia coli possesses aspartic proteinase activity. AB - We amplified the human T-cell leukemia virus type 1 (HTLV-1) protease gene fragment by polymerase chain reaction (PCR) and cloned it into a pUC plasmid vector. DNA sequencing data of the protease gene fragment indicated that it contained an open reading frame capable of encoding the active HTLV-1 protease. To express a fusion protein of beta-galactosidase linked with the HTLV-1 protease in Escherichia coli, a plasmid DNA was constructed by inserting the HTLV-1 protease gene DNA into a procaryotic expression vector, pUEX2, consisting of a lacZ gene directed by a lambda phage Pr promoter and designated pUEX-pro. By Western blot analysis using anti-beta-galactosidase antibody, a bigger molecular size band than that of the control beta-galactosidase molecule was observed in E. coli cells transformed with pUEX-pro but not with control pUEX2, suggesting that the particular fusion protein was successfully expressed. This recombinant protease protein in the E. coli cell lysate was demonstrated to be able to cleave the decapeptide substrates composed of amino acid sequences containing proteolytic cleavage sites in the HTLV-1 gag precursor polyprotein. The gag precursor polyprotein expressed in the mammalian cells by the recombinant vaccinia virus system was also expectedly cleaved by this enzyme. Significant inhibition of this protease activity by pepstatin A, an aspartic proteinase specific inhibitor, confirms that HTLV-1 protease is a member of the aspartic proteinase group as suggested previously. Since the crude lysate without purification is utilized sufficiently as a native HTLV-1 protease reagent, this protease preparation is easily applicable to the large scale screening of HTLV-1 protease inhibitors for the treatment of diseases caused by HTLV-1. PMID- 8435043 TI - Sequence analysis of selected regions of the env (V3 loop and gp41) and gag (p7) reading frames of Ethiopian human immunodeficiency virus type 1 strains. AB - Amplified polymerase chain reaction (PCR) products, corresponding to the V3 loop and gp41 of the env, and p7 of the gag region, from proviral DNA of several Ethiopian and Swedish HIV-1 strains were sequenced. Of the six amino acids (GPGRAF) that constitute the principal neutralizing determinant (PND) within the V3 loop, the Ethiopian isolates all showed two amino acid changes (GPGQTF). Four to five other substitutions were found in the amino acids flanking the PND. Substitution of alanine (A) for threonine (T) should result in a change in the predicted secondary structure, i.e., disappearance of a coil structure. Percentage similarity data on a stretch of 22 amino acids within the V3 loop showed a concordance of the Ethiopian HIV-1 isolates with the sequences of published macrophage-T-cell tropic HIV isolates. Additionally derived protein sequences in two other regions showed two common substitutions in p7 and one to two substitutions in gp41 compared to a recent consensus sequence. These changes are hitherto unique for the Ethiopian strains, and suggest the presence of a clustering of a divergent HIV-1 strain in Addis Ababa, Ethiopia. PMID- 8435044 TI - Characterization of rabies glycoprotein expressed in yeast. AB - The rabies virus surface glycoprotein was synthesized in Saccharomyces cerevisiae using an expression vector which contains an inducible promoter from the copper metallothionein gene. The rabies G protein was also expressed constitutively in yeast when cloned under control of the triose dehydrogenase promoter. Polypeptides of 65-68 kDa, which migrated at the same molecular weight as authentic viral rabies G protein species, were synthesized by yeast transformants as detected by immunoblotting with rabies specific antiserum. In addition, these polypeptides were immunoprecipitated with several rabies G-specific monoclonal antibodies which neutralize virus infectivity. The recombinant rabies G proteins were glycosylated and associated with membranes in yeast. When injected into guinea pigs, yeast extracts containing the rabies G protein protected animals from lethal rabies virus challenge when administered intramuscularly. However, the same material did not protect mice from a lethal rabies intracerebral challenge. PMID- 8435045 TI - Primary and secondary structure of a 360-nucleotide isolate of potato spindle tuber viroid. AB - Full-length complementary DNAs (cDNA) of a mild (KF5) and a severe (S-PSTVd) isolate of potato spindle tuber viroid (PSTVd) were constructed. DNA sequencing of four KF5 cDNA clones (M3, M4, M5, and M7) revealed that KF5 is comprised of 360 nucleotides. By comparison, all three cDNA clones (S2, S9, and S10) of S PSTVd possess 359 nucleotides. Sequence microheterogeneity was observed among the KF5 cDNA clones. Clone M5 differs from mild PSTVd isolate KF6 by a U-to-A transversion at position 303 followed by an A addition at the lower half of the "virulence-modulating" (VM) region. These changes modified the PSTVd consensus sequence of the VM region from 5' UCUAUCU 3' to 5' UCAAAUCU 3'. Additionally, clones M4 and M7 have a G-to-A transition at position 65 of the pathogenic domain, and M3 has a G-to-A transition at position 133 of the variable domain. The sequence of the three cDNA clones of S-PSTVd was identical to that of PSTVd isolate 440-1. An improved computer program was used to predict the secondary structure of the above two sequence variants as well as that of other PSTVd variants of which the structure has been reported previously. The data provides support for the hypothesis that increasing thermodynamic instability of the VM region is correlated with increasing virulence of the respective naturally occurring PSTVd isolate. PMID- 8435046 TI - Deduced amino acid sequences at the fusion protein cleavage site of Newcastle disease viruses showing variation in antigenicity and pathogenicity. AB - The amino acid sequence at the F2/F1 cleavage site of the F0 fusion protein of 17 strains of Newcastle disease virus (NDV) was deduced from sequencing a 32 nucleotide area of the genome by reverse transcription and polymerase chain reaction (PCR) techniques. With the addition of sequences at the same area previously published for 9 other viruses comparisons were made of a total of 26 NDV strains and isolates (11 of low virulence, 15 of high virulence or mesogenic) covering ten antigenic groups determined by reactions with monoclonal antibodies. All the virulent viruses and the mesogenic strain Komarov showed the amino acid sequence 112R/K-R-Q-K/R-R116 for the C-terminus of the F2 protein and phenylalanine (F) at the N-terminus of the F1 protein, residue 117. The mesogenic isolate of the antigenic variant NDV responsible for the recent panzootic in racing pigeons, often termed "pigeon paramyxovirus type 1", examined in this study had the sequence 112G-R-Q-K-R-F117. The deduced amino acid sequence in the corresponding region of all viruses of low virulence was 112G/E-K/R-Q-G/E-R-L117. The virulent virus, PMV-1/chicken/Ireland/34/90 (34/90), which had a close antigenic relationship to a group of avirulent viruses, three of which were examined in the present study as representatives of the monoclonal antibody group H, showed between 4-6 nucleotide differences from these viruses in the 32 nucleotide region studied. These resulted in differences in the deduced amino acid sequence at residue 112 E-->K, 115 E-->K and 117-->F, giving 34/90 a typical virulent virus motif at the cleavage site. Despite the extremely small portion of the genome studied there were several areas which appeared characteristic for 34/90 and the three group H viruses of low virulence, which suggests that they may have arisen from the same gene pool. PMID- 8435047 TI - Identification of a new mumps virus lineage by nucleotide sequence analysis of the SH gene of ten different strains. AB - The SH gene and its flanking sequences have been analysed for 10 strains of mumps virus (MuV) and compared to 5 others. A new lineage has been identified among UK isolates. Changes in the transcription pattern could not be correlated with differences in the sequences of the F-SH and SH-HN intergenic regions of the genome. PMID- 8435048 TI - The biological basis of the menopause. AB - Age-related changes occur throughout the reproductive lifespan of normal healthy women. From the age of 20, the menstrual interval gradually shortens and becomes increasingly regular until the perimenopause. This is related to a shortening of the follicular rather than the luteal phase of the cycle. Serum FSH concentration is elevated during the follicular phase in older women who are still menstruating regularly, while serum inhibin levels are decreased in both the follicular and luteal phases. The relationship between FSH secretion, ageing and feedback inhibition by oestradiol, inhibin, or other presently unmeasured factors in women with regular menses, remains to be elucidated. The primary factor influencing the transition from regular menses to the perimenopause and subsequent menopause appears to be the size of the residual primordial follicle pool. Fecundability begins to decline by the age of 29 years. There is considerable evidence from the experience gained in assisted fertilization procedures that this is related to the effect of age on the quality of the oocyte rather than on the endometrium. At the time of the last menses, few follicles remain. There are no endocrine markers to signal the last cycle. Hence, menopause can only be identified retrospectively when there is no further menses. The probability of being menopausal increases with the duration of amenorrhea and age. Considerable evidence suggests that both serum FSH and serum inhibin are biomarkers of the number and/or quality of follicles remaining in the ovary. There is also evidence that the age of menopause, itself, is a potent biomarker of the general ageing state of the individual. PMID- 8435049 TI - Hormone replacement therapy and cancer. PMID- 8435050 TI - Osteoporosis: pathogenesis, diagnosis, prevention and management. AB - Osteoporosis has emerged as a major and increasing health problem requiring interventions at both the individual and community levels. Most cases of osteoporosis are found among women after the menopause, since menopausal status and age are key predictors of fracture risk. This review has focused particularly on osteoporosis occurring in postmenopausal women: the magnitude of the problem, how it occurs, how it is diagnosed, strategies in prevention and treatment. The diagnosis of osteoporosis and identification of individuals with heightened fracture risk due to osteopenia have been greatly facilitated by the development of dual energy X-ray absorptiometry, a simple, safe, highly precise technique for bone density measurement. Where possible, intervention strategies in osteoporosis have been related to what is known about the pathogenesis of bone loss, especially the management of modifiable risk factors. Oestrogen deficiency of any cause results in accelerated bone turnover, with an increase in the rate of net bone loss. Exogenous oestrogens can control this form of bone loss. In established osteoporosis, hormone replacement therapy can achieve clinically significant gains in bone mass. Consideration of hormone replacement therapy is pivotal in preventive and therapeutic strategies. Issues other than osteoporosis must be taken into account when hormone replacement is considered. Attention to other modifiable risk factors, both in the lifestyle and of a medical nature, is also indicated. A number of promising agents for the treatment of established osteoporosis are described. However, available data on fracture prevention by these agents are limited. There is concern that an ideal therapy for established osteoporosis may not be achievable. Therefore, strong emphasis is placed on the need for osteoporosis prevention now and in the foreseeable future. Although much has been learnt in recent years, more research is needed in the long-term prediction of fracture risk, broadly-applicable measures to reduce the prevalence of osteoporosis, and targeted interventions for individuals at high risk. PMID- 8435051 TI - The evolution of menopausal symptoms. PMID- 8435052 TI - The practicalities of hormone replacement therapy. AB - An appropriate regimen of HRT using oestrogen with or without progestogen can be found for the majority of patients. In many cases this will be the first or second therapy that is chosen and for most women will be one of the combination packs that are commercially available. In a significant number of patients, however, these formulations will either not control symptoms or bleeding or will cause unacceptable progestogenic side-effects. Separate prescribing of oestrogen and progestogen will then be required. We suspect that the reported low compliance of women taking HRT in the general population may be related to the deficiencies of the available combination packs and reluctance of physicians to separately prescribe the oestrogen and progestogen components of HRT. The latter is understandable as the literature contains so few guidelines concerning prescribing. It is hoped that progestogens that have less side-effects than the C 19 steroids (currently universally used in combination packs of HRT) will be incorporated into new formulations. The option of prescribing oestrogens to non hysterectomized women in the form of continuous combined therapy is not available to many physicians because the necessary endometrial sampling every 12-18 months cannot be arranged; the current outpatient methods of sampling require experience of manipulation of instruments within the uterine cavity that is usually only acquired during gynaecological training. There are still many uncertainties about the appropriate combination of oestrogen and progestogen that should be incorporated into a continuous combined regimen to avoid the troublesome bleeding that occurs in a significant proportion of women when starting this therapy. Many previous studies were seriously flawed and further research, carefully designed and conducted, is urgently needed. PMID- 8435053 TI - Oestradiol and testosterone implants. PMID- 8435054 TI - Hormone therapy following breast and uterine cancer. AB - Cancers of the breast and endometrium, although hormonally-dependent, are not complete contraindications to hormonal replacement therapy. About 70% of women with endometrial cancer will be completely cured of their disease using appropriate surgical techniques and therefore can be given oestrogen without in any way compromising their long-term survival. In fact oestrogen will probably allow such women to survive longer with a higher quality of life. Most postmenopausal women with cancer of the breast should be offered an impeded oestrogen such as tamoxifen as their first line of hormonal treatment. There may be improvement in the vagina and bone calcium content following the use of this 'anti-oestrogen' but some women will continue to suffer from vasovagal symptoms. Women with breast cancer which is small, node-free and relatively non-aggressive may also do well on HRT. Because of the influence of progestogens in reducing oestrogen receptor production, in reducing the expression of various growth factors and in inducing apoptosis, it is wise to administer high-dose progestogens to these women as well as oestrogen. There is no clinical evidence that HRT administered to such women will induce any increase in tumour growth or recurrence. Women with a disease-free survival of 10 or more years can also be regarded as 'cured' and can also be offered oestrogen in conjunction with high dose progestogens. Finally, those women with known secondary spread but who are severely disadvantaged by their oestrogen deficiency symptoms should be offered high-dose progestogens first and if their symptoms persist, then have oestrogen added to the regimen till the symptoms subside. PMID- 8435055 TI - Running a menopause clinic. AB - A menopause clinic can be run either by a general practitioner as a primary referral clinic or in a hospital by a team of specialists and paramedical personnel as a secondary referral centre. Both can be run efficiently and with sensitivity. The importance of giving adequate information and education through combined video, written and verbal information is stressed. The partner should be included where possible. Self-assessment and monitoring of menopausal symptoms facilitates titration of the therapy, control of side-effects and compliance. Although all normal health checks, e.g. cervical smear and mammography should be offered, their frequency is not influenced by the use of HRT and medicolegally no extra laboratory tests are required before or after prescription of HRT. However, some extra selected tests can be useful such as lipid profile, liver enzymes and bone densitometry. A menopause clinic should offer comprehensive counselling on all lifestyle factors such as smoking, exercise, diet, alcohol and stress factors. Liaison with other health professionals such as physicians, psychiatrists, social workers, physiotherapists and dietitians, enhances the opportunity for appropriate counselling in selected cases. However, for most women personalized care by an informed general practitioner over 3-4 visits will allow titration of therapy, adequate counselling and a high rate of compliance. Compliance is also helped by a 5-7 day-a-week question line where telephone queries can be dealt with quickly by trained staff. PMID- 8435056 TI - Predictors of menopausal symptoms: psychosocial aspects. AB - The most relevant factors influencing a woman's quality of life during the menopausal transition appear to be her previous emotional and physical health, her social situation, her experience of stressful life events (particularly bereavements and separations), as well as her beliefs about the menopause. Specific predictors of vasomotor symptoms include surgical menopause and possibly current cigarette smoking. The role of stress, past menstrual problems and reports of hot flushes earlier in life as predictors requires further study. There are considerable cultural differences in the reporting of vasomotor symptoms which may be explained by the meaning ascribed to them and the value of older women in societies, as well as possible dietary, lifestyle and genetic differences. Those who seek medical help for menopausal problems tend to report more physical and psychological problems in general. They are more likely to be under stress and to hold particular beliefs about the menopause. These personal and social issues need to be addressed in their own right and should not be automatically attributed to the menopause. Clinical psychologists and counsellors, ideally working as part of the team, can help women and couples to clarify the nature of the problems and to help them to explore solutions. In contrast to childbirth, preparation for the menopause has been neglected in the development of services, as well as in research (Notelovitz, 1988; Hunter, 1990c). The studies reviewed here do suggest some pointers for health promotion; these are being evaluated in a current study by Hunter and Liao and can be summarized as follows: 1. Providing balanced information about the menopause, to women and their families. 2. Discussion of attitudes towards the menopause, with reassurance of overly pessimistic beliefs. 3. Health promotion sessions focusing upon diet, exercise and smoking (factors which are associated with general health and the development of osteoporosis). 4. Stress management sessions. 5. Group discussion of personal, health and social issues met by women during midlife. PMID- 8435057 TI - Oestrogens and atherosclerotic vascular disease--local vascular factors. PMID- 8435058 TI - Oestrogens and atherosclerotic vascular disease--lipid factors. AB - Cardiovascular disease remains the major cause of death for postmenopausal women in Western societies. The majority of epidemiological studies indicate that postmenopausal oestrogen replacement therapy is associated with a 50% reduction in the risk of cardiovascular disease, with much of the reduction being mediated by changes in the plasma concentration of cholesterol within high and low density lipoproteins. In addition to favourably influencing the plasma concentration of lipoproteins, oestrogens also influence the complex metabolism of lipoproteins in the arterial wall, helping to impede the formation of the atherosclerotic plaque. Whilst oestrogens alter endothelial function, vascular reactivity and fibrinolysis, these changes are also seen with reduction of LDL cholesterol and may partly reflect the altered concentration of plasma lipoproteins induced by oestrogens. Oral oestrogens have substantially greater favourable effects on LDL and HDL cholesterol than their transdermal counterparts but also result in greater hypertriglyceridaemia. Most progestogens antagonize the beneficial effects of oestrogens on lipoproteins in a dose-dependent manner; however, cyclical use of low doses of progestogens with an oral oestrogen generally retains a net beneficial effect. Lipoprotein levels fluctuate during cyclical therapy, the most adverse changes being noted at the end of the progestogen phase. Lipoprotein concentrations are constant during continuous combined regimens which have the potential for more prolonged exposure to an adverse progestational effect. Despite adverse effects on the lipoprotein profile, animal studies suggest that progestogens do not substantially reverse the beneficial effects of oestrogens on the development of atherosclerosis. Finally, oestrogen therapy may be useful in the management of postmenopausal women with hyperlipidaemia, and also in the secondary prevention of clinical sequelae in women with established atherosclerosis. PMID- 8435059 TI - Epidemiological overview of oestrogen replacement and cardiovascular disease. AB - In contrast to numerous epidemiological studies of prevention in men, there has been limited research into the prevention of cardiovascular disease in women. Nevertheless, sufficient data have accumulated showing that OeRT does protect against circulatory disease in women, although evidence regarding the true magnitude of that protection remains incomplete. The best estimates of the relationship between OeRT and CVD come from population-based prospective studies which are remarkably consistent: overall they indicate a 40% reduction in CVD with use of OeRT. However, because of the underlying better health of the postmenopausal women who use hormone replacement therapy, this result probably overestimates the benefit of OeRT by an unknown degree. Furthermore, details of OeRT formulation (especially the influence of regimens with an added progestin), dose, duration, and route of administration have not been adequately studied, and the evidence regarding the effect of OeRT on rates of stroke is equivocal and requires clarification. Oestrogen's cardioprotection appears to derive from favourable effects on serum lipoprotein profiles. There may also be a direct effect on the arterial system. Detrimental influences of OeRT on haemostatic function seem unlikely. Definitive information about the actual size of effects of commonly-used regimens of OeRT on cardiovascular disease and intermediate endpoints such as serum lipid concentrations can only be obtained through large scale randomized controlled trials. Even if the reduction in CVD were modest, the mortality rates of CVD in our society are still so high that widespread use of oestrogen replacement therapy would result in substantial numbers of women's lives being saved. PMID- 8435060 TI - Altered expression of cytochrome P-450 mRNAs, and potentially of other transcripts encoding key hepatic functions, are triggered during the isolation of rat hepatocytes. AB - The abundance of 12 cytochrome P-450 (CYP) mRNAs was quantified in the caudate lobe of rat livers before dissociation of the organ into single cells by perfusion with 0.025% (w/v) collagenase. Comparison of the initial abundance of CYP-1A1, -1A2, -2A subfamily, -2B1/2, -2C7, -2C11, -2D subfamily, -2E1, -3A1/2 and -4A1 transcripts in the caudate lobe of the intact liver with the values found in freshly isolated hepatocytes demonstrated that the relatively brief (1 h) cell isolation and washing procedures routinely caused 2-3-fold increases in the mRNAs encoding CYP-1A2, -2B1/2, -3A1/2, and -4A1, concomitant with a 50% decline in CYP2C11 mRNA. Further changes in the expression of CYP mRNAs occurred when the hepatocytes were cultured. Thus CYP1A1 mRNA, which is not constitutively expressed in rat liver, became detectable in hepatocytes cultured for 1 h, and after 6 h CYP3A1/2 mRNA levels began to increase. In contrast, levels of all other CYP mRNAs studied had declined after 24 h of culture concomitant with the loss of total cytochrome P-450 content. Culture of hepatocytes with 0.5 mM metyrapone (which prevents the loss of total P-450 content) increased CYP1A1 and CYP3A1/2 mRNA levels still further, such that after 72 h of culture these transcripts were conservatively 10-18-fold higher than in hepatocytes prior to culture. This suggests that these two isoenzymes comprise the bulk of the total cytochrome P-450 content maintained by metyrapone. Collectively, these results demonstrate that the technique commonly used to isolate rat hepatocytes alters hepatic gene expression, as illustrated by the elevation of the mRNAs encoding CYP-1A2, -2B1/2, -3A1/2 and -4A1, and that such perturbations are exacerbated during culture under standard conditions by the loss of the constitutive CYP2C11 and the precocious induction of CYP1A1 and CYP3A1/2 mRNAs. PMID- 8435061 TI - Cloning and characterization of the rat bone sialoprotein gene promoter. AB - To study the transcriptional regulation of the rat bone sialoprotein (BSP) gene, the nucleotide sequence of a approximately 1 kb HindIII/KpnI subfragment from a genomic clone containing the 5' flanking sequence, exon 1 and part of intron 1 was determined and the transcription start site defined. This region includes an inverted TATA element (nt -24 to -19), an inverted CCAAT box, a homeobox-binding site, a putative 1,25-dihydroxyvitamin D3 response element (VDRE) sequence overlapping the inverted TATA sequence, and a novel 18 nt palindrome that may control the tissue-specific transcription of the BSP gene. The shortest promoter sequence capable of directing bacterial chloramphenicol acetyltransferase reporter gene expression included the inverted TATA element and the inverted CCAAT box. However, the promoter activity was down-regulated by 1,25 dihydroxyvitamin D3, indicating that the unique VDRE-like sequence overlapping the TATA element is functional. Thus the rat BSP gene promoter is characterized by novel cis-acting elements that may be involved in hormone- and tissue-specific regulation of transcription. PMID- 8435062 TI - A polylysine-induced aggregation of substrate accompanies the stimulation of casein kinase II by polylysine. AB - Casein kinase II (CK-II) activation by polylysine parallels an aggregation of substrates promoted by the polycation. CK-II is known to be stimulated by basic polypeptides and polyamines. The mechanism by which this stimulation takes place, however, is not yet fully understood. Here we show that, in the usual CK-II assay, polylysine induces the aggregation of casein. This aggregation has been monitored by turbidimetry, electron microscopy and gel filtration. The polylysine concentration-dependence of the casein aggregation parallels the polylysine concentration-dependence of the enzyme stimulation. In the presence of polylysine the enzyme is incorporated into the casein aggregates promoted by the polycation, thus supporting the view that this substrate aggregation is directly related to the mechanism of CK-II stimulation. Preliminary results show that a similar parallelism occurs with other natural substrates of the enzyme. The physiological meaning of this substrate aggregation, and its possible relation to other polylysine-stimulated enzymes and polylysine-aggregated proteins, are discussed. PMID- 8435063 TI - Eicosanoid/thromboxane A2-independent and -dependent generation of lysoplasmenylethanolamine via phospholipase A2 in collagen-stimulated human platelets. AB - Collagen-induced human platelet stimulation is dependent on the release of arachidonic acid (AA) from membrane phospholipid and the formation of thromboxane A2 (TxA2) for TxA2-induced platelet activation. Since plasmenylethanolamine represents the single major phospholipid reservoir of AA in resting human platelets, we assessed its hydrolysis via phospholipase A2 upon platelet stimulation with low levels of collagen by determining the generation of [3H]lysoplasmenylethanolamine via eicosanoid/TxA2-independent and -dependent processes. Ethanolamine phospholipids in platelets were prelabelled with [3H]ethanolamine before stimulation with either collagen or the TxA2 mimetic U46619, in the presence or absence of BW755C, a dual inhibitor of the cyclooxygenase/lipoxygenase activities, or GR32191B, a TxA2-receptor antagonist. Collagen stimulation promoted a marked generation of [3H]lysoplasmenylethanolamine, which was only moderately decreased when TxA2 synthesis or TxA2 receptors were blocked by BW755C or GR32191B respectively. The moderate rise in [3H]lysoplasmenylethanolamine formation with U46619 as the agonist was only slightly affected by BW755C and blocked by GR32191B. Evidence for eicosanoid/TxA2-independent and -dependent generation of [3H]lysophosphatidylethanolamine was also obtained. A significant quantitative loss of AA from plasmenylethanolamine was also demonstrated in collagen stimulated platelets. The present findings indicate the activation of plasmenylethanolamine cleavage via phospholipase A2 in collagen-stimulated human platelets, which, to a considerable extent, does not depend on eicosanoid/TxA2 synthesis. This may represent an important source of releasable AA for TxA2 generation and the promotion of further liberation of AA and phospholipid mediated signalling pathways. PMID- 8435064 TI - Anionic charge concentration of rat kidney glomeruli and glomerular basement membrane. AB - Estimates of levels of glomerular and glomerular-basement-membrane anion charge should serve as useful quantitative markers for the integrity of the tissues in health and disease. We have developed a simple, rapid, technique to measure this charge through the use of ion exchange with radioisotopes 22Na+ and 36Cl- at low ionic strengths in phosphate buffer. When this technique is used, normal glomeruli isolated from rat have a measured net anion charge concentration of 17.4 +/- 3.7 p-equiv. per glomerulus (n = 20). Perfused rat kidneys that lose approximately half of their glomerular heparan [35S]sulphate content (owing to oxygen-radical damage) exhibited a lower anion charge, of 7.5 +/- 1.6 p-equiv. per glomerulus (n = 5). Glomerular basement membranes prepared from rat glomeruli by a sonication-centrifugation procedure in the presence of enzyme inhibitors had a charge concentration of 6.3 +/- 0.7 mu-equiv./g wet wt. of tissue (n = 4), whereas membranes prepared by sonication, centrifugation, DNAse and detergent treatment had a charge concentration of 7.1 +/- 1.6 mu-equiv./g wet wt. (n = 4). Isotope-dilution experiments with 3H2O on these detergent-prepared glomerular basement membranes demonstrated that they had a water content of approx. 93%, which would then give a net anion charge concentration of 7.6 +/- 1.7 m-equiv./l (n = 4). These values are in good agreement with those obtained by others using titration techniques [Bray and Robinson (1984) Kidney Int. 25, 527-533]. The relatively low magnitude of glomerular anion charge in normal kidneys is consistent with other recent findings that glomerular anion charge is too low to affect the glomerular transport of charged molecules in a direct, passive, biophysical manner through electrostatic interactions. PMID- 8435065 TI - Hyperosmolarity leads to an increase in derepressed system A activity in the renal epithelial cell line NBL-1. AB - Hyperosmolarity induced an increase in Na(+)-dependent L-alanine uptake in confluent monolayers of the established renal epithelial cell line NBL-1. This induction was attributable to system A and was only seen when the cells had been previously deprived of amino acids in the culture medium to derepress system A activity. It was additive to the adaptive regulation induction, and both were inhibited by cycloheximide. However, the hyperosmolarity effect was inhibited by colcemid (an inhibitor of microtubular function), but adaptive regulation was not. Otherwise, when cell monolayers were incubated in a control medium, basal Na(+)-dependent L-alanine uptake mediated by system B0 decreased. The results of this study show that: (i) system A activity was not induced by cell shrinkage and subsequent swelling due to extracellular hyperosmolarity when cells were incubated in control medium; (ii) previous expression of system A activity induced by amino acid starvation seems to be a prerequisite for further induction due to hyperosmolarity; and (iii) the effects of adaptive regulation and hyperosmotic stress are mediated by different mechanisms. PMID- 8435066 TI - Comparison of the levels of inositol metabolites in transformed haemopoietic cells and their normal counterparts. AB - We have compared the levels of inositol metabolites in three pairs of normal and transformed cells which have been matched with respect to their cell lineage, differentiation and proliferation status: (i) normal human myeloid blast cells and the human promyelocytic leukaemic cell line, HL60; (ii) human umbilical-cord T-helper cells and C8166 cells, a HTLV-1-transformed T-helper cell line; and (iii) an interleukin 3-dependent long-term culture of murine pro-B-cells (BAF3) and BAF3 cells transformed by transfection with the bcr-abl oncogene. Complex patterns of inositol metabolites were present in each of the cell populations. Although there were a number of differences in the levels of certain inositol metabolites between individual cell populations in the paired groups, we did not observe any consistent difference in the levels of inositol metabolites between the proliferating normal and transformed cells. In particular, our data do not support the reported correlation between elevated glycerophosphoinositol (GroPIns) levels and transformation of cells by membrane and cytoplasmic oncogenes which has been reported by other workers. All the cells contained high concentrations of Ins(1,3,4,5,6)P5 (between 12 and 55 microM) and InsP6 (between 37 and 105 microM). The HTLV1-transformed T-helper cells had particularly high levels of total inositol phosphates (predominantly GroPIns, an unidentified inositol bisphosphate and InsP6). The observations are discussed with reference to cell transformation and to the differentiation status of the paired populations. PMID- 8435067 TI - Human lysosomal alpha-glucosidase: functional characterization of the glycosylation sites. AB - N-linked glycosylation is one of the important events in the post-translational modification of human lysosomal alpha-glucosidase. Phosphorylation of mannose residues ensures efficient transport of the enzyme to the lysosomes via the mannose 6-phosphate receptor. The primary structure of lysosomal alpha glucosidase, as deduced from the cDNA sequence, indicates that there are seven potential glycosylation sites. We have eliminated these sites individually by site-directed mutagenesis and thereby demonstrated that all seven sites are glycosylated. The sites at Asn-882 and Asn-925 were found to be located in a C terminal propeptide which is cleaved off during maturation. Evidence is presented that at least two of the oligosaccharide side chains of human lysosomal alpha glucosidase are phosphorylated. Elimination of six of the seven sites does not disturb enzyme synthesis or function. However, removal of the second glycosylation site at Asn-233 interferes dramatically with the formation of mature enzyme. The mutant precursor is synthesized normally and assembles in the endoplasmic reticulum, but immunoelectron microscopy reveals a deficiency of alpha-glucosidase in the Golgi complex and in the more distal compartments of the lysosomal transport pathway. PMID- 8435068 TI - A protein kinase inhibitor, staurosporine, enhances the expression of phorbol dibutyrate binding sites in human polymorphonuclear leucocytes. AB - Staurosporine, a potent protein kinase C (PKC) inhibitor, was studied for its effects on the binding of phorbol 12,13-dibutyrate (PDBu) to human polymorphonuclear leucocytes (PMNs). Treatment of PMNs with staurosporine concentrations in the range 50 nM-2 microM at 37 degrees C (but not at 4 degrees C) and with 1 nM [3H]PDBu at both temperatures enhanced specific PDBu binding to PMNs by approx. 10-600% relative to control values. The potentiation was rapid (detectable within 1 min) and reached a plateau after 10 min of cell treatment. Scatchard analysis of the binding showed that staurosporine increased the total number of PDBu-binding sites (Bmax) from (178 +/- 9) x 10(3) (control) to (324 +/ 15) x 10(3) sites per PMN and lowered the apparent dissociation constant (Kd) from 9.6 +/- 0.8 (control) to 3.3 +/- 0.3 nM. In Ca(2+)-depleted cells, staurosporine induced similar changes in Kd values, whereas the Bmax. increased by 60%. Treatment of PMNs with 500 nM staurosporine enhanced PDBu binding in the particulate fraction by 120 +/- 7% and decreased PDBu binding in the soluble fraction by 69 +/- 4%, whereas PKC histone-phosphorylating activity of both fractions was almost completely inhibited. Incubation of staurosporine-pretreated particulate fractions with soluble fractions enriched the particulate fraction in PDBu-binding sites at the expense of the soluble fraction, without altering the binding affinity of PDBu for either fraction. Stimulation of PMNs with chemotactic N-formyl peptides induced a transient increase in PDBu binding. This effect was potentiated by approx. 52% by staurosporine. These results show that, in addition to its interference with PKC protein-phosphorylating activity, staurosporine enhances both PDBu-binding capacity and affinity to PMNs, through a mechanism involving Ca(2+)-dependent and -independent processes. Alterations of PDBu binding to soluble and particulate fractions suggest that the enhanced binding capacity in intact PMNs may be due to translocation of PDBu receptors, presumably PKC units. This phenomenon may affect PKC-dependent cellular responses mediated by physiological stimulation. PMID- 8435069 TI - Cholesterol increase in mitochondria: its effect on inner-membrane functions, submitochondrial localization and ultrastructural morphology. AB - The effect of cholesterol incorporation on some functions of the mitochondrial inner membrane and on the morphology of rat liver mitochondria was studied. Basal ATPase and succinate dehydrogenase activities remained unchanged after cholesterol was incorporated into the mitochondria; however, uncoupled ATPase activity was partially inhibited. The presence of several substrates and inhibitors did not change the amount of cholesterol incorporated, which was localized mostly in the outer membrane. Electron-microscope observations revealed the presence of vesicles between the outer and inner membranes; these vesicles increased in number with the amount of cholesterol incorporated. The data suggest that cholesterol induces the formation of vesicles from the outer membrane, and modifies the activity of stimulated ATPase. PMID- 8435070 TI - Purification and immunochemical characterization of a male-specific rat liver oestrogen sulphotransferase. AB - Sulphation of oestrogens represents an important regulatory mechanism for these biologically active compounds. We have characterized and purified a form of rat liver sulphotransferase (ST), existing as a 32,500 Da monomer, which sulphates oestrogens, and have used this preparation to produce antibodies against oestrogen ST. The enzyme was active against oestrone, oestriol and beta oestradiol, but not towards androgens. Using the antibody as a probe for immunoblotting, it was determined that the enzyme is expressed solely in male rats, and predominantly in the liver. Of the tissues examined, the only major extrahepatic tissue found to have any oestrogen ST was the brain (although the levels were very low), indicating that there might be a role for the sulphation of oestrogens in the brain. Examination of human liver and platelet cytosols by immunoblotting showed that the antibody recognized two major proteins of 32 and 34 kDa, which were presumed to correspond to the two principal phenol ST isoenzymes present in man. PMID- 8435071 TI - Formation of peroxides in amino acids and proteins exposed to oxygen free radicals. AB - Dilute aqueous solutions of BSA or lysozyme gave positive tests for peroxides after exposure to reactive oxygen species. The reactive species were generated by gamma-irradiation, reduction of H2O2 with Fe2+ ions or thermal decomposition of an azo compound. Peroxides were assayed by an iodometric method. Identification of the new groups as hydroperoxides was confirmed by their ability to oxidize a range of compounds and by the kinetics of their reaction with iodide. The hydroperoxide groups were bound to the proteins and their yields (G values) corresponded to 1.2 -OOH groups per 100 eV of radiation energy absorbed for BSA, and 0.8 for lysozyme. The oxygen free radicals effective in protein peroxidation were the hydroxyl and organic peroxyl, but not superoxide or its protonated form. The efficiency of BSA peroxidation initiated by the hydroxyl radicals was 40%. Protein peroxides decayed spontaneously with a half-life of about 1.5 days at 20 degrees C. Exposure of the common amino acids to hydroxyl free radicals showed that six of them (glutamate, isoleucine, leucine, lysine, proline and valine) were peroxidized with similar efficiency to the proteins, whereas the rest were inert or much less susceptible. These results suggest that some proteins may be peroxidized by a variety of agents in vivo and that their subsequent reactions with protective agents, such as ascorbate or glutathione, may decrease the antioxidant potential of cells and tissues. PMID- 8435072 TI - Sodium-dependent co-transported analogues of glucose stimulate ornithine decarboxylase mRNA expression in LLC-PK1 cells. AB - Non-metabolizable analogues of glucose, including 1-O-methyl alpha-D glucopyranoside (alpha MDG), that are co-transported with Na+ increase the specific activity of ornithine decarboxylase (ODC) in LLC-PK1 cells [Lundgren and Vacca (1990) Am. J. Physiol. 259, C647-C653]. The present study examines the effect of alpha MDG on LLC-PK1-cell ODC mRNA expression. The relative concentration of ODC mRNA in cells incubated in Earle's balanced salts solution minus glucose (EBSS--G) plus 3 mM alpha MDG was 5-6-fold higher than the concentration of ODC mRNA in cells incubated in either EBSS--G alone or in EBSS- G plus 3 mM 3-O-methyl-D-glucopyranose, a non-metabolizable analogue of glucose that is taken up by a passive carrier-mediated glucose transporter. Actinomycin D and cycloheximide completely blocked the increase in ODC activity induced by alpha MDG. Actinomycin D was also a potent inhibitor of ODC mRNA expression by alpha MDG. Cycloheximide had very little effect on the ability of this sugar to increase ODC mRNA. The relative concentration of ODC mRNA increased as a function of the incubation time in EBSS--G plus alpha MDG. The amount of ODC mRNA also increased as a function of the concentration of alpha MDG in EBSS--G. The addition of phlorizin (100 microM) to EBSS--G prevented alpha MDG from increasing ODC mRNA in LLC-PK1 cells. Phlorizin did not prevent phorbol 12-myristate 13 acetate (PMA) from enhancing LLC-PK1-cell ODC mRNA expression. The positive effect of both alpha MDG and TPA on ODC mRNA expression was suppressed when cells were incubated in hypertonic EBSS--G. From these results it is suggested that the uptake of Na(+)-dependent cotransported sugars increase ODC activity by enhancing ODC gene transcription and that this process may be dependent on cell volume expansion. PMID- 8435073 TI - pH-dependence of warfarin binding to alpha 1-acid glycoprotein (orosomucoid). AB - The binding of warfarin to alpha 1-acid glycoprotein (AAG) was found to increase with decreasing pH. The u.v.-visible difference spectra generated upon binding to AAG at pH 5.0 or 7.4 showed warfarin to bind as the anion. Warfarin-binding data were satisfactorily fitted to a model that incorporates the effect of pH and discriminates the association constants of the non-protonated and protonated binding site of the protein. It was shown that AAG-binding site in the protonated form had a markedly higher affinity for warfarin than the non-protonated form, with a pK value of 7.7 +/- 0.1, which is likely to be a histidine residue. Among other possible interactions, it is suggested that ligand binding to AAG involves a reinforced hydrogen bond. PMID- 8435074 TI - Location of close contacts between Escherichia coli RNA polymerase and guanine residues at promoters either with or without consensus -35 region sequences. AB - Methylation-interference assays have been used to identify guanine residues that make important contacts with RNA polymerase during open-complex formation at two related Escherichia coli promoters. Methylation of lower-strand G-31 at a gal consensus promoter completely prevents complex formation, while modification of upper-strand G-33 has no detectable effect. At galP1, which lacks a consensus -35 region, modification of lower-strand G-33 and upper-strand G-14 reduces, but does not prevent, complex formation. G-33 is the only guanine residue in the -35 region of galP1 where modification interferes with open-complex formation. Since this guanine residue is not protected in open complexes, we conclude that its modification causes alteration of, or interference with, a transient contact during the transcription initiation pathway. PMID- 8435075 TI - Direct desaturation of intact galactolipids by a desaturase solubilized from spinach (Spinacia oleracea) chloroplast envelopes. AB - In plants, polyenoic fatty acids are synthesized by desaturase enzymes which use acyl groups of membrane lipids as substrates. To provide direct 'in vitro' evidence for this reaction, we solubilized envelope membranes from spinach (Spinacia oleracea) chloroplasts with Triton X-100 to release a membrane-bound n 6 desaturase. In the presence of oxygen and reduced ferredoxin, the solubilized enzyme desaturated a variety of substrates, such as free oleic acid, free erucic acid, 1-oleoyl-sn-glycerol 3-phosphate and the three galactolipids 1-oleoyl-2-(7' cis-hexadecenoyl)-3-beta-D-galactopyranosyl-sn-glycerol, 1,2-dioleoyl-3-beta-D galactopyranosyl-sn-glycerol and the ether analogue 1,2-di-(9'-cis-octadecenyl)-3 beta-D-galactopyranosyl-sn- glycerol. The in vitro desaturation of these exogenously added complex lipids with ester- and ether-linked substrate chains is unambiguous evidence for lipid-linked desaturation. The enzyme measures the insertion of the new double bond from the methyl end and the existing (n-9)-cis double bond of an appropriate acyl or alkyl chain. The distal part of the substrate group, normally the carboxy end of a fatty acyl residue, is of less importance and, in particular, its activation in thioester form is not required. PMID- 8435076 TI - New patterns of diacylglycerol metabolism in intact cells. AB - The metabolism of di[1-14C]octanoylglycerol metabolism was examined in four cell lines: NIH 3T3 fibroblasts, BHK cells, Pam 212 keratinocytes and WEHI 3BD+ cells. We found the direct conversion of 1,2-di[1-14C]octanoyl-sn-glycerol ([14C]diC8) into dioctanoylphosphatidylcholine and dioctanoylacylglycerol, but no formation of phosphatidylinositol. The [14C]diC8 also underwent lipolytic breakdown. In contrast, 1-[1-14C]oleoyl-2-acetyl-sn-glycerol was metabolized exclusively by lipolysis. Our findings support a new scheme for the metabolic termination of diacylglycerol signals. PMID- 8435077 TI - Antisera specific for D2 dopamine receptors. AB - Antisera have been raised against two peptides from the sequence of D2 dopamine receptors: peptide 1 from the predicted second extracellular loop and peptide 2 from the predicted third intracellular loop. The antisera recognize specifically a 95 kDa band in Western blots of several bovine brain regions, which corresponds to the denatured D2 dopamine receptor, whereas in recombinant CHO cells expressing D2 dopamine receptors a 80 kDa band is seen. The antisera immunoprecipitate 10-20% of the D2 dopamine receptors from soluble preparations of bovine brain. The antisera recognize D2 dopamine receptors in immunofluorescence analyses of recombinant CHO cells bearing the receptor gene. The antisera directed against the third intracellular loop, but not those against the second extracellular loop, will interfere with the coupling of D2 dopamine receptors and G-proteins in bovine brain preparations. PMID- 8435078 TI - Effect of thiol compounds on human complement component C4. AB - Thiol compounds have been investigated as inhibitors of the covalent binding reaction of human complement protein C4 using Sepharose-C1s as a combined activating and binding surface. o- and p-substituted aminothiophenols are equally effective inhibitors, whereas the m-substituted compound is a less potent inhibitor. The anti-hypertensive drug captopril is also shown to inhibit the covalent binding reaction. A comparison of the effects of these compounds on the covalent binding reaction of isolated C4A and C4B has been made. Results suggest that a Pro-to-Leu substitution in C4B is likely to account for the differences in inhibitory potency of C4B compared with C4A observed with the aromatic inhibitors. PMID- 8435079 TI - 1,4-Bis[2-(3,5-dichloropyridyloxy)]benzene, an extremely potent modulator of mouse hepatic cytochrome P-450 gene expression. AB - We have investigated the effects of TCPOBOP (1,4-bis[2-(3,5- dichloropyridyloxy)]benzene), a potent cytochrome P-450-inducing agent [Poland, Mak, Glover, Boatman, Ebetino and Kende (1980) Mol. Pharmacol. 18, 571-580], on cytochrome P-450 isoenzyme expression in the mouse. Hepatic cytochrome P-450s from several distinct gene families were strikingly induced by a single dose of 75 micrograms of the compound. Northern-blot analysis demonstrated that this induction was almost certainly due to transcriptional activation of the cytochrome P-450 genes. The potency of this inductive effect was further reflected in the finding that cytochrome P-450 levels were still increased 12 weeks after a single injection of 75 micrograms of this compound. Interestingly, the mRNA levels of certain other genes, including those of metallothionein and the mouse major urinary proteins, were also induced. In view of the similarity in the effects of TCPOBOP and the synthetic glucocorticoid dexamethasone on mouse hepatic gene expression, we determined whether TCPOBOP acts through the glucocorticoid receptor. This did not, however, appear to be the case. Experiments with hypophysectomized animals demonstrated that TCPOBOP action was not regulated indirectly via the pituitary. In addition, induction of mouse Cyp2b protein by TCPOBOP in a primary culture of mouse hepatocytes suggests that the compound has a direct action on mouse liver. The above findings demonstrate that TCPOBOP is one of the most potent modulators of cytochrome P-450 gene expression described to date. It is not inconceivable that a single dose of this compound may alter hepatic gene expression for the majority of the lifespan of a mouse. PMID- 8435080 TI - Effect of dexamethasone on gluconeogenesis, pyruvate kinase, pyruvate carboxylase and pyruvate dehydrogenase flux in isolated hepatocytes. AB - Treatment of 18 h-starved rats with dexamethasone and subsequent isolation and incubation of the hepatocytes in the presence of the steroid increased gluconeogenic flux with both 1.0 mM pyruvate and 1.0 mM lactate plus 0.2 mM pyruvate as the substrate. The magnitude of stimulation was comparable with both substrates. The increase in glucose output was accompanied by an increased flux through pyruvate carboxylase, although the absolute flux and magnitude were considerably less in the presence of the more reduced substrate. The effect of the steroid on the flux through pyruvate dehydrogenase was substrate-dependent, an inhibition occurring with the more oxidized substrate. There was no effect of steroid treatment on [1-14C]lactate or pyruvate oxidation or on tricarboxylic acid-cycle flux as measured by [3-14C]pyruvate oxidation. Dexamethasone treatment resulted in a parallel increase in both pyruvate kinase flux and glucose synthesis with both substrates employed, indicating that the steroid had no effect on the partitioning of phosphoenolpyruvate between pyruvate and lactate formation and gluconeogenesis. Similarly there was no effect of the steroid on either the activity ratio or the total pyruvate kinase activity in the cells. It is suggested that the acute effect of the dexamethasone to increase gluconeogenesis resides at the level of phosphoenolpyruvate formation, i.e. pyruvate carboxylase and possibly phosphoenolpyruvate carboxykinase. PMID- 8435081 TI - Fulvic acid supplementation and selenium deficiency disturb the structural integrity of mouse skeletal tissue. An animal model to study the molecular defects of Kashin-Beck disease. AB - High concentrations of fulvic acid and selenium deficiency are the main causative factors of Kashin-Beck disease, an endemic, chronic and degenerative osteoarticular disorder found in China. In the search for an animal model of this disease, mice were exposed to these pathogenetic conditions for two generations and the collagen types from skin, bone and cartilage were analysed. The growth of the treated mice was slightly retarded, and the rate of reproduction was lower in animals maintained on a fulvic acid-supplemented and/or selenium-deficient diet. Irregular bone formation was seen by radiography and morphometry. Biochemical analysis indicated that lysine residues in collagen I from bone and in collagen II from cartilage were overmodified. The values of Hyl/(Hyl+Lys) in bone collagen alpha 1(I) chains from treated mice were about 0.434-0.484, i.e. substantially higher than that of the control (0.277). The values of this parameter for collagen II were 0.482 for control and 0.546-0.566 for treated mice. The melting temperature of collagen I from bones of treated mice was 1 degrees C lower than that of control collagen, indicating decreased thermal stability. The breakage point of the tibiae of treated mice occurred at a lower preload force than for controls, suggesting that the overmodified and thermally less stable collagen molecules are causally related to a lower mechanical strength of bones. PMID- 8435082 TI - Mode of action of endoglucanase III from Trichoderma reesei. AB - Endoglucanase III (EG III) was purified to homogeneity from the culture medium of Trichoderma reesei QM 9414. It has a molecular mass of 48 kDa, and an isoelectric point of 5.1. Maximal activity was observed between pH4 and 5. Celloligosaccharides and their chromophoric derivatives were used as substrates, and the reaction products were analysed by quantitative h.p.l.c. Nucleophilic competition experiments (between methanol and water) allowed unequivocal assessment of cleavage sites. EG III preferentially released cellobiose (or the corresponding glycoside) from the reducing end of the higher cellodextrins. A putative binding model containing five subsites is proposed. The pH-dependence of 4'-methylumbelliferyl beta-cellotrioside hydrolysis indicates the presence of a protonated group with a pK 5.5 in the reaction mechanism, and the possible involvement of a carboxy group is corroborated by a temperature study (delta Hion = -15.9 J/mol). This, together with independent evidence from affinity-labelling experiments [Tomme, Macarron and Claeyssens (1991) Cellulose '91, New Orleans, Abstr. 32] and n.m.r. studies [Gebbler, Gilkes, Claeyssens, Wilson, Beguin, Wakarchuk, Kilburn, Miller, Warren and Withers (1992) J. Biol. Chem. 267, 12559 12561], favours the assumption of a lysozyme-type (retention of configuration, two essential carboxy groups) mechanism for this family A cellulase. PMID- 8435083 TI - The effects of thimerosal on calcium uptake and inositol 1,4,5-trisphosphate induced calcium release in cerebellar microsomes. AB - Thimerosal inhibits calcium uptake in skeletal muscle sarcoplasmic reticulum and rat cerebellar microsomes by inhibiting the Ca(2+)-ATPase. In the presence of 5 mM dithiothreitol (DTT), Ca2+ uptake and ATPase activity were not inhibited by thimerosal, indicating that thimerosal modifies cysteine residues of the Ca(2+) ATPase. Low thimerosal concentrations (2 microM) sensitize the inositol 1,4,5 trisphosphate (InsP3)-sensitive Ca2+ channel, making it open at lower InsP3 concentrations. Higher concentrations of thimerosal, however, cause inhibition of InsP3-induced Ca2+ release. Both sensitization and inhibition of the InsP3 receptor by thimerosal can be prevented by DTT. The binding and metabolism of InsP3 by cerebellar microsomes is not affected by thimerosal. The amount of InsP3 induced Ca2+ release is co-operatively linked to the InsP3 concentration with a Hill coefficient of 2.0 +/- 0.3. This is decreased to 1.0 +/- 0.2 at inhibitory concentrations of thimerosal. Under our experimental conditions, we observed no dependence of quantal Ca2+ release on intraluminal Ca2+ concentration. PMID- 8435084 TI - Proteolytic removal of three C-terminal residues of actin alters the monomer monomer interactions. AB - Homogeneous preparations of actin devoid of the three C-terminal residues were obtained by digestion of G-actin with trypsin after blocking proteolysis at other sites by substitution of Mg2+ for the tightly bound Ca2+. Removal of the C terminal residues resulted in the following: an enhancement of the Mg(2+)-induced hydrolysis of ATP in low-ionic-strength solutions of actin; an increase in the critical concentration for polymerization; a decrease in the initial rate of polymerization; and an enhancement of the steady-state exchange of subunits in the polymer. Electron microscopy indicated an increased fragility of the filaments assembled from truncated actin. The results suggest that removal of the C-terminal residues increases the rate constants for monomer dissociation from the polymer ends and from the oligomeric species. PMID- 8435085 TI - Hypocholesterolaemic effect of beta beta'-methyl-substituted hexadecanedioic acid (MEDICA 16) in the male hamster. AB - Treatment of cholesterol-fed male hamsters kept on a diet of purina chow with beta beta'-methyl-substituted hexadecanedioic acid (MEDICA 16) resulted in a progressive hypocholesterolaemic effect, amounting to a 50% decrease in the cholesterol content of all plasma lipoproteins. The decrease in plasma cholesterol could be accounted for by activation of plasma-cholesterol efflux through the liver into the bile mediated by MEDICA 16-induced (a) increase of the number of liver LDL receptors, (b) activation of liver neutral cholesteryl ester hydrolase with a concomitant inhibition of liver acyl-CoA cholesterol acyltransferase, resulting in shifting of the liver cholesteryl ester/free cholesterol cycle in the direction of free cholesterol, and (c) activation of cholesterol efflux from the liver into the bile. The increase in bile cholesterol output was accompanied by an increase in bile phospholipids but not in bile acids. In contrast with rats, MEDICA 16-treatment of male hamsters did not result in a hypotriacylglycerolaemic effect, inhibition of lipogenesis, nor in a substantial decrease in plasma apolipoprotein C-III content. PMID- 8435087 TI - Enzymatic and non-enzymatic sulfation mechanisms in the biological actions of minoxidil. PMID- 8435086 TI - Involvement of calcium in modulation of neutrophil function by phorbol esters that activate protein kinase C isotypes and related enzymes. AB - In this study, the effects of a series of phorbol esters with different spectra of biological activities and different patterns of activation of the isoenzymes of protein kinase C (PKC) have been studied in human neutrophils. The aim was to gain more information on which isoenzymes of PKC are involved in neutrophil activation, specifically inhibition of fMet-Leu-Phe (fMLP)-stimulated bivalent cation influx and stimulation of O2-. release (either alone or potentiation of the response to fMLP). Prior addition of both phorbol 12-myristate 13-acetate (PMA) and sapintoxin A (SAPA) inhibited fMLP-stimulated Mn2+ influx. Higher concentrations of resiniferatoxin (RX) were also inhibitory, inhibition being more apparent at longer preincubation times. However, 12-deoxyphorbol 13-O phenylacetate (DOPPA) showed only a slight inhibitory effect and required a prolonged preincubation. PMA, SAPA and RX, but not DOPPA, stimulated O2-. release by themselves. Lower concentrations of PMA, SAPA and RX, which were ineffective alone, considerably potentiated O2-. release stimulated by fMLP, whereas DOPPA had little or no effect. These results rule out a major role for PKC-delta (not activated by SAPA) and PKC-beta 1 (activated by DOPPA), but suggest the involvement of RX kinase in addition to PKC in the inhibition of fMLP-stimulated Mn2+ influx and potentiation of fMLP-stimulated O2-. release. However, when the cytosolic free Ca2+ concentration ([Ca2+]i) was elevated with the Ca2+ ionophore ionomycin, DOPPA was able to stimulate O2-. release, which probably reflects the known Ca2+ requirement for activation of PKC-beta 1 by DOPPA in vitro. The effects of the other phorbols were also enhanced when [Ca2+]i was elevated; all of the phorbols synergize, to variable extents, with Ca2+ to activate PKC in vitro. Enhancement of RX-stimulated O2- release by elevation of [Ca2+]i was unexpected, since RX kinase has been reported to be inhibited by high concentrations of Ca2+ in vitro. Finally, use of fura-2 and SK&F 96365 to manipulate the fMLP-stimulated rise in [Ca2+]i showed that when fMLP was able to evoke its normal rise in [Ca2+]i (to a peak of 700-900 nM), O2-. release was potentiated by PMA, SAPA and RX. However, when fMLP was only able to evoke a small increase in [Ca2+]i (to a peak of 400 nM), potentiation by PMA was unaffected but potentiation by SAPA and RX was considerably reduced. This observation agrees with published data demonstrating that activation of PKC in vitro by SAPA is more Ca(2+)-dependent than activation by PMA.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8435088 TI - Effect of bile acids on intracellular calcium in isolated rat hepatocyte couplets. AB - The effects of bile acids on cytosolic free calcium ([Ca2+]i) were studied in single isolated rat hepatocyte couplets using a scanning laser cytometer and the fluorescent dye, indo-1. Cholestatic bile acids, chenodeoxycholate (CDC) and taurolithocholate (TLC) increased [Ca2+]i in a dose-dependent manner. Choleretic bile acids, tauroursodeoxycholate (TUDC) and taurocholate (TC), did not induce any change in [Ca2+]i except TC at very high doses. Treatment with TUDC added concomitantly with CDC or TLC significantly decreased the rise in [Ca2+]i induced by bile acids. These results, obtained with a polarized hepatocyte model that secretes bile, confirmed that cholestatic bile acids increase [Ca2+]i and showed that TUDC inhibits this phenomenon. These data are in agreement with a key role of intracellular calcium in cholestasis. PMID- 8435089 TI - The expression of UDP-glucuronosyltransferases of the UGT1 family in human liver and kidney and in response to drugs. AB - The expression of human UDP-glucuronosyltransferase (UGT) 1 gene family in the liver and kidney was examined using specific enzyme activity, antibodies and DNA probes for each of the four family members. Phenol UGT HP1 was expressed at a similar, relatively low, abundance in each liver and kidney whereas phenol UGT HP4 was more highly expressed in the kidney. Bilirubin UGTs (HP2 and HP3) were not detectable in the kidney and HP3 was the major isoform in the liver. The UGT activities towards certain specific substrates correlated well with the respective mRNA levels in the tissues. Bilirubin UGT HP3 was induced 2-3-fold in the livers from patients treated with phenytoin and phenobarbital. Storage of a human liver in University of Wisconsin solution which contains dexamethasone and insulin caused a large accumulation of all the UGT mRNAs, but these were not quantitatively translated into expressed UGT activities. The implications of these results are discussed. PMID- 8435090 TI - Sex differences in the diabetes-induced modulation of rat hepatic cytochrome P450 proteins. AB - Sex differences in the diabetes-induced changes in hepatic cytochrome P450 proteins were investigated in rats treated with streptozotocin. Changes in specific cytochrome P450 proteins were monitored using diagnostic substrates and immunologically utilizing specific polyclonal antibodies. When expressed in terms of nmoles of total cytochrome P450, ethoxyresorufin O-deethylase activity was increased by treatment with streptozotocin, the extent of induction being the same in the two sexes. In contrast, lauric acid hydroxylase and ethylmorphine N demethylase activities were induced only in the male rat. Finally, p-nitrophenol hydroxylase and pentoxyresorufin O-dealkylase were enhanced by the same treatment in both sexes, the effect being more pronounced in the male. These findings indicate that sex-specific changes in certain cytochrome P450 proteins exist in response to insulin-dependent diabetes but these cannot, however, be ascribed to sex differences in the severity of diabetes induced by streptozotocin since the degrees of hyperketonaemia and hyperglycaemia were the same in the two sexes. These are likely to reflect sex-specific differences in growth hormone and triglyceride levels in the diabetic animals. PMID- 8435091 TI - Metabolism of iron from (3,5,5-trimethylhexanoyl)ferrocene in rats. A dietary model for severe iron overload. AB - The feeding of diets enriched with (3,5,5-trimethylhexanoyl)ferrocene (TMH ferrocene) has been shown recently to produce a severe experimental iron overload in rats and has been considered as an adequate animal model for hereditary haemochromatosis in humans. We synthesized three 59Fe-labelled ferrocene compounds with different lipophilic characters (ferrocene, TMH-ferrocene, and 1,1'-bis(3,5,5-trimethylhexanoyl)ferrocene [(TMH)2-ferrocene]) and studied the metabolism of iron from these compounds in comparison with the hydrophilic ferrous sulphate in rats with iron deficiency, and normal and increased iron stores. The bioavailability of iron from TMH-ferrocene (whole body retention, 48% from a 5 mg Fe dose) was twice as high as from ferrocene and six times higher than from (TMH)2-ferrocene and ferrous sulphate. In contrast to the well-known iron salts (ferrous sulphate), the intestinal absorption of TMH-ferrocene iron was independent from the dose (1 or 5 mg Fe) and similar in iron-deficient and iron-loaded rats, indicating that the intestinal absorption of the TMH-ferrocene is not regulated by the body iron stores. After intestinal absorption, TMH ferrocene iron in the portal blood is transported to the liver independently from transferrin. In contrast to absorbed ferrocene, iron from TMH-ferrocene is almost completely released from the hydrocarbon moiety within the liver. Depending on the body iron stores, TMH-ferrocene iron is then incorporated preferentially into haemoglobin (iron-deficient rats) or added to the iron stores in the liver (iron loaded rats). A transient storage of the 59Fe-label in fat tissue was observed only from oral ferrocene but not from TMH-ferrocene. Due to the outstandingly high bioavailability of TMH-ferrocene, the chronic feeding of this compound resulted in a fast and progressive iron overload in rats (liver iron: 16.9 mg Fe/g wet weight after 10 weeks of feeding a diet containing 0.5% TMH-ferrocene), and can be regarded as the best characterized and most useful animal model for severe hepatocellular iron overload in humans. PMID- 8435092 TI - Down-regulation of multiple cytochrome P450 gene products by inflammatory mediators in vivo. Independence from the hypothalamo-pituitary axis. AB - Inflammatory stimuli suppress constitutive hepatic expression of the CYP2C11 and CYP2C12 genes in male and female rat livers, respectively. Because growth hormone (GH) is an important regulator of P450 gene expression in the rat, the effects of bacterial endotoxin injection in hypophysectomized rats were compared to those in normal animals. In intact females, 0.2 mg/kg endotoxin suppressed total P450 and hepatic expression of CYP2C6, CYP2C7, CYP2C12, and CYP2E1 mRNAs, as well as CYP2C12 and CYP2E1 proteins, measured 16 hr later. CYP2C7 and CYP2E1 mRNAs were most affected (17 and 13% of untreated levels, respectively). Endotoxin treatment also induced the mRNA for the hepatic acute phase protein, haptoglobin, to 260% of control female levels. In hypophysectomized females supplemented with GH infusion, endotoxin caused the same or greater effects on expression of the P450 and haptoglobin gene products than were observed in the intact animals. It is concluded that the P450 suppression observed after endotoxin administration can occur independently of an effect on pituitary hormone secretion. PMID- 8435093 TI - Interaction of halichondrin B and homohalichondrin B with bovine brain tubulin. AB - Halichondrin B is a polyether macrolide of marine origin which binds to tubulin and inhibits microtubule assembly in vitro and in vivo. As is the case with phomopsin A and dolastatin 10, halichondrin B is a non-competitive inhibitor of vinblastine binding to tubulin. Analogous to maytansine, which by contrast is a competitive inhibitor of vinblastine binding, halichondrin B has no effect on colchicine binding, which is greatly stabilized by phomopsin A and dolastatin 10, but not by maytansine. We have previously developed assays which allow sensitive discrimination among the interactions of various ligands with tubulin, and examined the effects of ligands on the reactivity of tubulin sulfhydryl groups and the exposure of hydrophobic areas on the surface of the tubulin molecule. To classify the nature of the interaction between halichondrin B and tubulin, in this study we examined the effects of halichondrin B and its closely related analogue, homohalichondrin B, by these assays. We found that: (1) halichondrin B and homohalichondrin B both inhibited formation of an intra-chain cross-link between two sulfhydryl groups in beta-tubulin, as do phomopsin A, dolastatin 10, maytansine, and vinblastine; (2) halichondrin B resembles maytansine in that it had no effect on alkylation of tubulin sulfhydryl groups by iodoacetamide, unlike phomopsin A, dolastatin 10 and vinblastine, all of which inhibit alkylation; (3) halichondrin B differs from other anti-mitotic drugs in that it enhanced exposure of hydrophobic areas on tubulin; (4) homohalichondrin B, like maytansine and in contrast to phomopsin A, dolastatin 10 and vinblastine, had no effect on exposure of hydrophobic areas; and (5) homohalichondrin B, contrary to maytansine, inhibited alkylation of tubulin sulfhydryl groups in the presence of GTP and MgCl2. In their interactions with the tubulin molecule, halichondrin B and homohalichondrin B appear to have unique conformational effects which differ from those of other drugs and also from the effects of each other as well. PMID- 8435094 TI - Molecular mechanisms of dibromoalkane cytotoxicity in isolated rat hepatocytes. AB - The cytotoxicity of dibromoalkanes to isolated hepatocytes was proportional to the dibromoalkane concentration and increasing chain length of the dibromoalkane (C2-C6). The rapid hepatocyte glutathione (GSH) depletion which occurred upon addition of the dibromoalkanes was also dependent on the concentration and chain length of the dibromoalkane. When added to hepatocytes, dibromoalkanes also caused a loss in protein sulfhydryl groups. After a lag period, lipid peroxidation occurred before the onset of cytotoxicity. Antioxidants or removing the oxygen from the medium markedly delayed dibromoalkane cytotoxicity. Bromoaldehydic metabolites formed by cytochrome P450-dependent mixed-function oxidases were probably responsible for lipid peroxidation as deuterated 1,2 dibromoethane (d4-DBE) induced less lipid peroxidation and was less cytotoxic even though GSH was depleted as rapidly and as effectively. Hepatocytes were also more resistant to dibromoalkanes if cytochrome P450 isoenzymes were inactivated with SKF 525A or methyl pyrazole. Furthermore, hepatocyte susceptibility to dibromoalkanes was increased markedly if aldehyde dehydrogenase was inactivated with disulfiram, cyanamide or chloral hydrate. Cytochrome P450-induced hepatocytes isolated from pyrazole-, phenobarbital- or 3-methylcholanthrene pretreated rats were also more susceptible to dibromoalkanes. These results suggest that dibromoalkane-induced cell lysis is due to lipid peroxidation as well as cytochrome P450-dependent formation of toxic bromoaldehydic metabolites which can bind with cellular macromolecules. Dibromoethane GSH conjugates also contribute to DBE cytotoxicity as depleting hepatocyte GSH beforehand increased hepatocyte resistance to DBE but not other dibromoalkanes. PMID- 8435095 TI - Effect of intrathecal morphine on the fate of glucose. Comparison with effects of insulin and xanthan gum in mice. AB - The hypoglycemic effect of morphine (40 micrograms) injected intrathecally (i.t.) was studied with regard to disposition of i.v. [14C]glucose and [3H]2 deoxyglucose and was compared with the effects of two other hypoglycemic agents, insulin (1 IU/kg, s.c.) and xanthan gum (50 mg/kg, i.p.). Mice given i.t. morphine or s.c. insulin exhaled a greater amount of 14CO2 from i.v. [14C]glucose than did control mice given i.t. saline, whereas there was less 14CO2 expiration in xanthan-treated mice. In morphine-treated mice there was less 14C in liver, brain and blood, and more 3H in kidney and hindleg muscle than in control mice. Insulin-treated mice had more 14C in muscle, less 14C in liver, brain, kidney and blood, and less 3H in liver and blood. In xanthan-treated mice, levels of both radiolabels were higher in liver, brain and kidney. Much lower glycogen content in muscle and depletion of liver glycogen occurred in morphine-treated mice, compared with control mice. Spinal transection completely inhibited the hypoglycemic effect of morphine, whereas adrenalectomy caused no inhibition. Morphine, insulin and xanthan appear to be acting by different mechanisms, although the hypoglycemic effects of both morphine and insulin appear to be due largely to an increased glucose uptake by muscle. PMID- 8435096 TI - 3-Carbamyl-N-allylquinuclidinium bromide. Effects on cholinergic activity and protection against soman. AB - 3-Carbamyl-N-allylquinuclidinium bromide (CAB) was synthesized and evaluated for its pharmacological effects on cholinergic activity and for protection in vivo against soman toxicity in guinea pigs. This carbamylated derivative of N-allyl-3 quinuclidinol (NAQ), a potent inhibitor of high-affinity choline uptake, demonstrated stereospecific alterations of cholinergic function as well as protection against soman. The R-isomer, but not the S-isomer, of CAB inhibited erythrocyte acetylcholinesterase (AChE) and plasma pseudocholinesterase (pChE) in a concentration-response manner (IC50 = 25 and 29 microM, respectively). The R isomer of CAB was also a more potent inhibitor of high-affinity choline uptake (IC50 = 4.8 microM) than S-CAB (IC50 = 63 microM). When R-CAB (10 mumol/kg, i.m.) was administered to guinea pigs 30 min prior to soman in conjunction with atropine (16 mg/kg, i.m.) given 1 min post-soman, the compound significantly reduced lethality up to 5 LD50S. This represents enhanced protection when compared to NAQ (up to 100 mumol/kg); the S-isomer of CAB failed to protect against soman intoxication. The results demonstrate that reversible inhibition of AChE with suppression of acetylcholine synthesis into a single compound, CAB, enhances the protection against organophosphates. PMID- 8435097 TI - Mechanism(s) regulating inhibition of thymidylate synthase and growth by gamma-L glutaminyl-4-hydroxy-3-iodobenzene, a novel melanin precursor, in melanogenic melanoma cells. AB - A proposed mechanism for the melanoma specific activity of phenolic amines is based upon the ability of the enzyme tyrosinase to oxidize these prodrugs to toxic intermediates. In this study, we synthesized an iodinated analog of gamma-L glutaminyl-4-hydroxybenzene (GHB) with increased antimelanoma activity in both human and murine melanoma cell lines. GHB and gamma-L-glutaminyl-4-hydroxy-3 iodobenzene (I-GHB) were shown to be substrates for both mammalian and mushroom tyrosinase. Glutathione, a cellular antioxidant, inhibited tyrosinase mediated formation of gamma-L-glutaminyl-3,4-benzoquinone (GBQ) from GHB, inhibited melanin production, and blocked the inhibition of the enzyme thymidylate synthase by oxidized GHB. Buthionine sulfoximine (BSO) depletion of cellular glutathione enhanced the growth inhibitory activity and the inhibition of in situ thymidylate synthase by phenolic amines in melanoma cells. GHB and I-GHB were shown to be approximately 5- and 10-fold more cytotoxic, respectively, in highly metastatic B16-BL6 cells than in weakly metastatic B16-F1 cells with approximately equal tyrosinase activity. B16-BL6 cells had approximately 20-fold higher gamma glutamyltranspeptidase (gamma-GTPase) activity than B16-F1 cells which suggested the possible involvement of this enzyme in the activation of the cytotoxicity of the phenolic amines. 4-Aminophenol, a product of gamma-GTPase reaction with GHB, was a substrate for tyrosinase and a potent inhibitor of in situ thymidylate synthase activity in melanogenic cells. In pigmented melanoma cells containing the enzyme tyrosinase, the quinone mediated mechanism of phenolic amine cytotoxicity may be uniquely important and the cellular antioxidant glutathione essential in the detoxification of these quinone-generated intermediates. PMID- 8435098 TI - Synergistic efficacy of O6-benzylguanine and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in a human colon cancer xenograft completely resistant to BCNU alone. AB - The DNA repair protein O6-alkylguanine-DNA alkyltransferase (alkyltransferase) repairs cytotoxic DNA damage formed by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). High levels of this repair protein cause tumor drug resistance to nitrosoureas. To investigate the ability of a direct alkyltransferase inhibitor, O6-benzylguanine, to reverse the nitrosourea resistance of human colon cancer cells, we studied the VACO 6 cell line which has high alkyltransferase and is completely resistant to BCNU at maximal tolerated doses in the xenograft model. O6-Benzylguanine at 0.5 microgram/mL for 1 hr inactivated VACO 6 alkyltransferase by > 98% and reduced the IC50 of BCNU by 3- to 4-fold. Further analysis indicated that these two agents act in a highly synergistic fashion. In xenograft bearing athymic mice, dose-dependent depletion of hepatic and tumor alkyltransferase was noted. To maintain alkyltransferase depletion in the xenograft for at least 24 hr, two doses of 60 mg/kg O6-benzylguanine were given 1 hr prior and 7 hr after BCNU. Under these conditions, VACO 6 xenografts became responsive to BCNU with significant reductions (P < 0.001) in the tumor growth rate. The combination increased toxicity to the host, reducing the maximum tolerated dose of BCNU by approximately 50%. This study provides definitive evidence that high alkyltransferase activity is responsible for BCNU resistance in human colon cancer xenografts and that with careful drug scheduling, O6-benzylguanine can sensitize a tumor which is completely unresponsive to BCNU alone. Further studies which optimize the therapeutic index of BCNU and O6-benzylguanine in vivo will define the schedule to be used in broader preclinical studies. PMID- 8435099 TI - Inhibition of phospholipase C delta by hexadecylphosphorylcholine and lysophospholipids with antitumor activity. AB - The antineoplastic compound hexadecylphosphorylcholine (HPC) was shown to be a highly effective inhibitor of phospholipase C delta (PLC delta 1), with an I50 of about 30 nmol/mL (30 microM) in the presence and absence of 200 microM spermine. A number of lysophospholipids, of which HPC can be considered to be a structural analog, also inhibited PLC. Lysosphingomyelin, lysophosphatidylserine, and lysophosphatidylcholine exhibited I50 values of 15, 10, and 7 nmol/mL, respectively, in the presence of 200 microM spermine. The I50 values were increased to 21-53 nmol/mL in the absence of spermine. N,N-Dimethylsphingosine and N,N,N-trimethylsphingosine, which inhibit the metastatic potential of human and murine tumor cells, were weak activators of PLC delta 1. It is postulated that HPC is more effective as an antineoplastic agent than lysophospholipids because HPC is metabolized slowly, while the lysophospholipids are metabolized rapidly in vivo. PMID- 8435100 TI - Antiplatelet activity of some prenylflavonoids. AB - Eight naturally occurring prenylflavonoids were tested for their antiplatelet activities in rabbit platelet suspension. Cyclomorusin and artomunoxanthone showed strong inhibition of platelet-activating factor (PAF; 1-O-alkyl-2-acetyl sn-glycero-3-phosphocholine) induced platelet aggregation. Cyclomulberrin, dihydroisocycloartomunin, cyclocommunol and cyclocommunin showed strong inhibition of arachidonic acid (AA)- and collagen-induced platelet aggregation. Cyclomorusin also inhibited markedly collagen-induced platelet aggregation. Cyclocommunin, dihydroisocycloartomunin and cyclomulberrin also showed slight but significant antiplatelet effects on the aggregation induced by PAF. Of the compounds tested, cyclocommunin exhibited the most potent inhibition of platelet aggregation induced by collagen (IC50 = 14.4 microM) and AA (IC50 = 12.5 microM). Thromboxane B2 formation caused by AA was suppressed by cyclocommunin and artomunoxanthone. PMID- 8435101 TI - Elevation of serum cholesterol levels in mice by the antioxidant butylated hydroxyanisole. AB - The food antioxidants butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) are structurally related to the hypocholesterolemic drug probucol. The purpose of this study was to determine if BHA can lower serum cholesterol levels as is observed with probucol. Treatment of mice with 0.75% BHA in their feed for 10 days resulted in a significant (P < or = 0.01) elevation of serum cholesterol levels. This effect contrasts with the cholesterol-lowering effect of probucol. Further, the degree of cholesterol elevation was comparable to that observed in mice administered 3% cholesterol in their feed for 7 days. The enzyme acyl CoA:cholesterol acyltransferase (ACAT) was decreased significantly (P < or = 0.01) in liver microsomes from BHA-treated mice. In contrast, hepatic microsomal ACAT activity was increased significantly (P < or = 0.01) in cholesterol-fed mice. These results suggested that the increased serum cholesterol observed in BHA-treated mice was not accompanied by an increase in hepatic cholesterol levels. Indeed, hepatic microsomal cholesterol levels were reduced in BHA-treated mice, but were increased significantly (P < or = 0.01) in cholesterol-fed mice. These results demonstrate that the common food additive BHA elevates serum cholesterol levels by a mechanism that apparently involves the decreased uptake of cholesterol by the liver. PMID- 8435102 TI - Comparative pharmacodynamics of CYP2B induction by phenobarbital in the male and female F344/NCr rat. AB - The phenobarbital dose-CYP2B induction response relationships and pharmacodynamics of CYP2B induction have been characterized in female and male F344/NCr rats. The ED50 and EC50 values for the induction, by phenobarbital, of hepatic CYP2B1 or 2B1/2B2 protein or associated catalytic activities (benzyloxy- or pentoxyresorufin O-dealkylation or testosterone 16 beta-hydroxylation) were 2- to 7-fold higher in the female than in the male rat, indicating a somewhat decreased potency for this effect in the female rat. In contrast, the maximal induction, expressed as the ratio of induced activity to control activity, was as great or greater in the female rat than in the male. Thus, any difference in the responsiveness of female rats to hepatic CYP2B induction by phenobarbital, compared to male rats, is reflected in potency but not degree of induction of catalytic activity or immunoreactive protein. PMID- 8435103 TI - Hematopoietic stem cell deficit of transplanted bone marrow previously exposed to cytotoxic agents. AB - High-dose chemotherapy and/or total body irradiation followed by autologous bone marrow rescue has improved the survival of patients with a variety of malignancies. Candidates for autologous bone marrow transplantation (ABMT) often have received prior exposure to cytotoxic agents, some of which may damage primitive stem cells. We have developed an in vivo murine model to evaluate the effects of a number of individual cytotoxic agents on the ability of syngeneic donor marrow to provide long-term hematopoiesis in recipients following high-dose total body irradiation. Marrow was experimentally obtained by giving donor mice 6 weekly injections of saline, cytosine arabinoside, cyclophosphamide, cisplatin, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), or busulfan, drugs known to have differing effects on primitive hematopoietic stem cells. After time to allow recovery of marrow and peripheral blood counts, 1 x 10(7) marrow cells from these mice were transplanted into lethally irradiated syngeneic recipients. Five to 6 months after marrow transplantation, the quality of long-term hematopoietic recovery was measured by WBC counts, marrow cellularity, CFU-S content, and determinations of stem cell self-renewal. Abnormalities were noted with the use of donor marrow exposed to all cytotoxic agents. Recipients of marrow previously exposed to cytosine arabinoside, an agent that spares the most primitive stem cells, were the least affected. Recipients of marrow previously exposed to busulfan, an agent known to damage primitive stem cells, were most affected with a decrease in peripheral blood counts, marrow cellularity, stem cell content, self-renewal capacity, and long-term survival. A decrease in hematopoietic stem cell self-renewal was seen in recipients of marrow previously exposed to cyclophosphamide, cisplatin, and BCNU even when marrow cellularity and CFU-S content were normal. These data suggest that the capacity of syngeneic donor marrow to provide long-term hematopoiesis in lethally irradiated recipients is dependent on its donor marrow primitive stem cell content. Long-term hematopoiesis may be severely compromised in recipients of donor stem cells previously exposed to cytotoxic agents which damage primitive stem cells. PMID- 8435104 TI - [Urinary tract infections. Recommendations with special emphasis on family practice]. AB - Clinical diagnosis can often indicate whether the patient has an infection of the lower or the upper urinary tract. The symptoms may be misleading, however. Examination of the urine is therefore essential. Recommendations are made for sampling, microscopy, stix-tests and interpretation of cultures. Species distribution and sensitivity patterns are presented. There has been a trend towards increasing antimicrobial resistance during the period 1982 to 1990. The recommended drugs for uncomplicated infections of the lower urinary tract in women include nitrofurantoin, amoxicillin, pivampicillin, pivmecillinam, sulfamethizole, trimethoprim and co-trimoxazole, with a possible preference for trimethoprim and nitrofurantoin (should be used with caution in elderly patients). Duration of therapy is normally three days. In pregnant women and in men with an infection of the lower urinary tract the duration of treatment should be 7-10 days. Specific drugs are recommended for these groups of patients. Drugs recommended for infection of the upper urinary tract and complicated infections of the lower urinary tract include amoxicillin, ampicillin, ciprofloxacin/ofloxacin, co-trimoxazole, pivampicillin and pivmecillinam. Duration of treatment should be 7-10 days. Treatment is also recommended for reinfection, for children, for patients with asymptomatic bacteriuria and for patients with permanent bladder catheters. Long-term prophylaxis and general advice on lifestyle are also discussed. PMID- 8435105 TI - Cell-cell communication and growth control of normal and cancer cells: evidence and hypothesis. PMID- 8435106 TI - Different levels of v-Ha-ras p21 expression in primary keratinocytes transformed with Harvey sarcoma virus correlate with benign versus malignant behavior. AB - Primary mouse keratinocytes transformed with an activated ras oncogene transduced by helper-free Harvey sarcoma virus (HaSV) form predominantly benign tumors. In contrast, keratinocytes transformed with helper-associated HaSV form malignant tumors. We report here that this different tumorigenic behavior correlated with a much higher level of v-Ha-ras p21 protein in cells transformed with the helper associated virus. The high level of v-ras expression in these cells was due to viral spread beyond the initial infection. The low level of v-ras p21 expression that resulted from single-hit infection with helper-free virus, together with the intrinsic heterogeneity of primary keratinocytes, explains, at least in part, the different tumorigenic behavior of keratinocytes transformed by the two types of viruses. PMID- 8435108 TI - Expression pattern of proteins that bind to the ultraviolet-responsive element (TGACAACA) in human keratinocytes. AB - We previously identified an ultraviolet (UV)-responsive element (URE; TGACAACA) that plays a role in both transcription and replication of polyoma sequences. Mouse polyclonal antibodies were raised against affinity-purified URE-bound proteins to characterize their expression patterns. These antibodies specifically recognized two of four URE-bound proteins, of 40 and 68 kDa. The 68-kDa protein was constitutively expressed in human keratinocytes, while the expression of the 40-kDa protein was induced by UV irradiation. Of the two, the 68-kDa protein bound to the URE with greater affinity than the 40-kDa protein, as determined by southwestern analysis. The expression of the 40-kDa protein increased as early as 1 h after UV irradiation of both rat fibroblasts and human keratinocytes and correlated with increased binding to the URE in an electrophoretic mobility shift assay. Other types of damage, as well as heat shock and serum stimulation, also induced the expression of this protein, suggesting that it may play a role in cellular response to stress or damage. The 40-kDa protein was expressed at the highest levels in the S phase of the cell cycle and was induced by aphidicolin, suggesting that it has a role in DNA replication. All together, these results suggest that exposure of human keratinocytes to damage- and stress-inducing agents modulates the expression of proteins that may play a role in regulating cellular response to DNA damage. PMID- 8435107 TI - Modulation of interleukin-1 alpha mRNA expression in mouse epidermis by tumor promoters and antagonists. AB - Increased expression of interleukin-1 (IL-1) in skin elicits a variety of responses, including inflammation and epidermal hyperplasia, which are also characteristic events elicited by tumor promoters. The goal of this study was to investigate whether various classes of tumor promoters increase expression of IL 1 alpha and whether phorbol ester-induced IL-1 alpha expression can be blocked by antitumor promoters. Northern analysis of mRNA isolated from the dorsal skins of SENCAR mice treated with 1 microgram of 4 beta-12-O-tetradecanoylphorbol-13 acetate (TPA) showed that a single application of TPA produced a significant increase in IL-1 alpha mRNA at 6 h that decreased by 24 h after treatment. Two treatments of TPA at 48-h intervals induced, at 6 h, twice as much IL-1 alpha mRNA as one treatment. Of the other promoters tested, anthralin (22.6 micrograms), mezerein (2 micrograms), calcium ionophore A23187 (120 micrograms), and benzoyl peroxide (20 mg) induced IL-1 alpha mRNA with different kinetics and to different extents. On the other hand, the non-tumor promoting phorbol ester analogue 4 alpha-12-O-tetradecanoylphorbol-13-acetate had little effect on the expression of IL-1 alpha mRNA. The effects of various antitumor promoters on TPA induced IL-1 alpha mRNA expression were also assessed. Fluocinolone acetonide, mepacrine, and 5,8,11,14-eicosatetraynoic acid were the most effective inhibitors, and each produced about 80% inhibition. Other antitumor promoters such as retinoic acid, N-tosyl-L-phenylalanine chloromethyl ketone, and butylated hydroxytoluene inhibited approximately 35%, 65%, and 50% of TPA-induced IL-1 alpha mRNA expression, respectively. Therefore, this study suggests a possible role of IL-1 alpha in the promotion stage of skin carcinogenesis. PMID- 8435109 TI - Reversal of ras-induced inhibition of gap-junctional intercellular communication, transformation, and tumorigenesis by lovastatin. AB - The plasma-membrane association and transforming activity of the ras oncoprotein p21 are dependent upon posttranslational farnesylation. Farnesyl synthesis and p21 ras farnesylation are inhibited by hydroxymethylglutaryl-CoA reductase inhibitors such as lovastatin. In this study, we examined whether lovastatin could reverse the transformed phenotype of a v-Ha-ras-transformed rat liver epithelial cell line (WB-ras cells) and if changes were associated with the enhancement of gap-junctional intercellular communication (GJIC). WB-ras cells grow in soft agar, have reduced GJIC, and are highly tumorigenic. Membrane association of p21 ras in these cells was inhibited after in vitro treatment with lovastatin (0.1-0.5 microM) for 48 h. Concomitantly, the cells displayed a more normal morphology, decreased growth in soft agar, and enhanced GJIC. These changes were prevented by cotreatment with mevalonic acid. The morphology and GJIC of rat liver epithelial cells transformed with other oncogenes (src, neu, and raf/myc) were not affected by lovastatin. Intrahepatic WB-ras tumors were induced in male rats by intraportal-vein injection of WB-ras cells. The size and DNA labeling index of these tumors were decreased approximately 75% by administration of lovastatin (5 mg/kg orally twice daily for 2 wk). These results suggest that lovastatin reversed the transformed phenotype of WB-ras cells by inhibiting p21 ras plasma membrane association. Furthermore, the concomitant enhancement of GJIC in lovastatin-treated cells suggests a role for reduced GJIC in the expression of the transformed phenotype. PMID- 8435110 TI - Evidence for Kupffer cell activation by burn injury and Pseudomonas exotoxin A. AB - Postburn metabolic and immunological alterations may in part be due to translocation of gut exotoxin and endotoxin, which can result in tumour necrosis factor (TNF) and prostaglandin E (PGE) production by macrophages. We evaluated the effect of burn injury, plus exotoxin and endotoxin on TNF-alpha and PGE production by Kupffer cells, and peritoneal macrophages. Adult Wistar rats underwent 30 per cent TBSA burn or sham burn. Kupffer cells were harvested from rat livers and peritoneal macrophages from the abdominal cavity 24 h postburn. They were cultured overnight at 1 x 10(6) cells/ml and stimulated with saline, 5 micrograms/ml of Pseud. aeruginosa Exotoxin A (Exo-A), 5 micrograms/ml of Pseud. aeruginosa Endotoxin (Endo), Exo-A + Endo, or Exo-A + Endo + the PGE derivative 16,16 dimethyl-PGE (dPGE) (10 micrograms/ml). The supernatants were harvested after 4, 24 and 48 h of culture and assayed for TNF-alpha and PGE. Results showed that burn injury induced an increase in TNF-alpha and PGE production by Kupffer cells stimulated with Exo-A, Endo, and both Exo-A + Endo (P < 0.05). The release of TNF-alpha by Kupffer cells was downregulated by exogenous PGE (P < 0.05). The increased TNF-alpha production was inversely related to PGE levels. In conclusion, both burn injury and Exo-A potentiate the responsiveness of Kupffer cells and peritoneal macrophages to endotoxin as measured by the rate of production of TNF-alpha and PGE. PGE may locally downregulate the immune response by limiting Kupffer cells' and peritoneal macrophages' TNF-alpha production. PMID- 8435111 TI - Historical notes on the use of pressure in the treatment of hypertrophic scars or keloids. PMID- 8435112 TI - Early diagnosis of staphylococcal toxaemia in burned children. AB - The features of toxic shock syndrome in burned children have been described in a review of seven patients (J. D. Frame et al., Burns 1985; 11, 234). These include a 'prodromal' 24-48 h period with diarrhoea, vomiting, general malaise, pyrexia, tachycardia and tachypnoea. The white cell count and haemoglobin concentration fall prior to the 'shock' phase, which occurs 3-4 days postburn. Once 'shock' has occurred the mortality of the condition is approximately 50 per cent; in the absence of 'shock' it is much reduced. We have undertaken a retrospective review of six burned children who were admitted in a 2-year period to the Mount Vernon NHS Trust Burns Unit with a clinical diagnosis of toxic shock syndrome. The evidence from our patients suggests that reliable early diagnostic signs are a rapidly developing severe pyrexia of 39.5 degrees C or above, and a simultaneously increasing tachycardia and tachypnoea to high levels. There is a sudden profound fall in the white cell count and haemoglobin concentration over a period of hours between 1 and 3 days from injury. Specific treatment should be instituted before the onset of 'shock'. The name staphylococcal toxaemia might promote earlier diagnosis and treatment of this condition and so reduce its mortality. PMID- 8435113 TI - Changes in diaphragm polyinositol phosphates caused by a large body surface area burn. AB - Respiratory problems are common among burn patients, and an understanding of the changes that occur in the phosphatidyl inositol signal transducing system (s.t.s.) in diaphragm muscle may identify pharmacological agents that would be useful in the treatment of these patients. This report examines changes that occur in polyinositol phosphates of diaphragm muscle due to the systemic effects of large (> 30 per cent) body surface area (per cent BSA) burns. Burn injury was applied to specific per cent BSA of the dorsal and ventral skin surfaces of mice. At postburn day 21, polyinositol phosphate levels were measured in the diaphragm by the incorporation of myo-[2-3H]inositol with separation of the phosphates by anion-exchange chromatography. All data were analysed using analysis of variance and curve fitting. In the diaphragm, levels of [3H]inositol, inositol-1,4,5 trisphosphate (IP3), inositol-1,4 bisphosphate (I1,4P2) and inositol-1 phosphate (I1P) increased with increasing burn size. Furthermore, a variety of independent relationships existed between the various phosphates in each burn group (i.e. control, 20 per cent and 50 per cent BSA burn). These data indicate that the systemic effects of burn trauma result in changes in the polyinositol phosphate part of the phosphatidyl inositol signal transducing system of diaphragm muscle. PMID- 8435114 TI - The psychiatrist on the burns unit. AB - The first 12 months of a new consultation-liaison service to a burns unit is described. Management of contact between the psychiatrist and the burns team is discussed and diagnostic categories are given for referrals seen. Diagnostic criteria are not achieved for many patients assessed, and yet the burns team still requires help managing patients who are psychologically disturbed. Education and a forum for team discussion are used as a way for the burns team to integrate psychological work in the management of their patients. PMID- 8435115 TI - Burn epidemiology: the Pink City scene. AB - This report describes the statistical analysis of 629 burn patients treated between January 1989 and August 1990. The analysed data include age, sex, cause of burn and mortality in relation to age, cause and extent of burn injuries. Additional information with regard to socioeconomic status, marital status, place of burn, family size, type of burn, time of accident and time between injury and hospital admission was obtained from analysis of 271 of the 629 patients admitted between January 1990 and August 1990. In our series, adolescent and young adults (11-40 years) comprised 64.8 per cent of the patients. Males formed 54 per cent and females 46 per cent of the total burns. 82.65 per cent of the patients received their burns at home. Most of our patients belonged to the low or lower middle socioeconomic strata and had large families. 95.5 per cent of the burns were accidental in nature. Flame burns comprised 67.9 per cent and scalds comprised 16.4 per cent of the total burns. The overall mortality rate was 48.3 per cent. The mortality rate was comparatively low in children (20.1 per cent). Flame burns resulted in maximum deaths (62.1 per cent). In patients with over 40 per cent burns, the mortality was about 80 per cent. There were no survivors in patients with over 70 per cent TBSA burns in our series. PMID- 8435116 TI - Temporal analysis of human leucocyte surface antigen expression and neutrophil respiratory burst activity after thermal injury. AB - Sepsis, the major cause of morbidity and mortality after burn injury, is related to multiple immune derangements. Using monoclonal antibodies and two-colour flow cytometry to identify surface antigens, peripheral blood mononuclear cell (PBMC) populations were analysed and correlated with lymphocyte proliferation assays for 21 days postinjury. In addition, in vitro expression of activation antigens by mitogen-stimulated PBMCs was analysed during the time period. Twenty-nine burn patients were studied, with burn injuries ranging from 19 to 97 per cent TBSA; PBMCs from human volunteers were used for control cells. Patients received aggressive enteral nutritional support starting day 1 postburn and underwent early excision and grafting of wounds; no patients developed sepsis during the study period. The most consistent changes in PBMCs after thermal injury were decreased percentages of total T cells (CD3+), T helper/inducer cells (CD4+), and T suppressor/cytotoxic cells (CD8+); the percentages of natural killer (CD16+) cells were not altered. Expression of surface 'activation' antigens on CD4+ and CD8+ cells (HLA-DR, interleukin-2 receptor and transferrin receptor) after mitogen stimulation was significantly depressed as early as 1 day postburn. An early monocytosis was seen on day 1 postburn, but decreases were found on days 4 and 7. Monocyte expression of HLA-DR antigen was suppressed throughout the study. Lymphocyte proliferation after mitogen stimulation and the responses of lymphocytes in mixed lymphocyte culture were suppressed postburn. Neutrophil respiratory burst responses were supranormal on days 1 and 7 postburn, but the differences were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8435117 TI - Laboratory data from the surveillance of a burns ward for the detection of hospital infection. AB - Nosocomial infection is a major problem affecting many hospital personnel and patients. Surveillance of intensive care areas such as burns wards is important due to the immunocompromised status of the patients. Since infection has been found to be a major cause of death in our burns ward, bacteriological surveillance of the area was carried out over a 1-year period. This indicated the various sources of infection, which included a contaminated container of disinfectant, and transient pathogenic flora on one of the staff members involved in changing dressings. Pseudomonas aeruginosa was the most commonly isolated pathogen from infected wounds as well as from the blood of patients developing sepsis. Autogenous spread of this organism was confirmed by similar pyocin typing results of the strains isolated from wounds, blood and faeces of the patients. Necessary changes were implemented based on these findings and the infection rate was reduced remarkably. The results suggested that strict vigilance by the personnel involved in the care of burns patients reduces the incidence of invasive sepsis and shortens the hospital stay. PMID- 8435118 TI - Prevention of hot tap water burns--a comparative study of three types of automatic mixing valve. AB - To prevent fatal outbreaks of Legionnaires' disease, particularly in hospitals and other health-care premises, building services engineers are recommended to store and operate hot water systems at a temperature of 60 degrees C. However, water at this temperature can cause serious scalding. It is therefore advised that mixing valves be installed in the hot water supply pipework to provide hot water at safe temperatures for washing and bathing. Electricity Association Technology Ltd (EATL) investigated the performance of three makes of automatic mixing valve. Tests showed that with constant supply conditions there was little difference in performance between the three valves when blending hot and cold water. However, the ability of the valves to respond to the loss of the cold water supply was quite valve was able, consistently, to shut the hot water off in the event of cold water failure. These results suggest that where it is necessary to safeguard people or patients against any risk of scalding, e.g. young children and handicapped patients, a quality thermostatic valve should be installed rather than a cheaper tempering valve. PMID- 8435119 TI - Acute adrenal insufficiency in the burn intensive care unit. AB - Acute adrenal insufficiency may underlie a confusing, stormy, intensive care unit course after a burn. The aetiology is most likely to be adrenal haemorrhage despite the absence of a coagulopathy. This report describes two patients who were diagnosed antemortem and successfully treated with replacement therapy. The aetiology, presentation, diagnosis and treatment of acute adrenal insufficiency in the intensive care unit is reviewed. PMID- 8435120 TI - Ocular chemical burns--clinical and demographic profile. AB - A clinical and demographic profile of 145 chemical eye injuries in 102 patients treated at a major referral centre of a developing country is analysed. The nature of the chemical agents, the occupation groups at risk and preventive measures for chemical injuries are emphasized. Forty-three patients (42.1 per cent) suffered bilateral injuries. Acids and alkalis together were responsible for 80 per cent of the chemical injuries. Young people working in laboratories and factories constituted two-thirds of the patients. Fifty-two eyes (35.9 per cent) suffered severe (Grade III/IV) injuries. Injuries caused by assault were more severe and proportionately lost more eyes. Visual outcome correlated with severity of injury at initial presentation. PMID- 8435121 TI - Prolonged allograft survival in a patient with extensive burns using cyclosporin. AB - A woman with very extensive burns (of over 75 per cent TBSA and 45 per cent full skin thickness) received cyclosporin to extend the survival of skin allografts obtained from several unmatched donors. The patients' wounds appeared completely healed after 3 months when the cyclosporin was discontinued. During the immunosuppressive treatment with cyclosporin there was no evidence of graft rejection or any side effects related to cyclosporin. Twelve days after discontinuing the drug rejection started. The burns were then successfully covered with autografts during two operations. The late functional results were excellent. PMID- 8435122 TI - Clinical application of adipofascial turn-over flaps for burn wounds. AB - Local adipofascial turn-over flaps overlaid with skin grafts were used successfully to reconstruct nine deep burn wounds following electric injuries or contact burns in seven patients. Durable flap coverage of the exposed tendons, joints or bones can be achieved with a one-stage procedure. Appropriate length-to width ratio and flap-to-base area ratio, and the tension-free insetting of the flap are essential for flap survival. The non-adherent characteristic of the adiposal component of the flap enables the underlying involved tendons or joints to glide through without adherence, and the rich vascular network in the fascia provides an ideal bed for the skin graft. The adipofascial turn-over flap is a reliable and simple technique for reconstruction of certain deep burn wounds if the surrounding soft tissue is available. The functional and cosmetic results in our series have been rewarding and satisfactory. PMID- 8435123 TI - Invasive burn wound infection due to Curvularia species. AB - A 3-year-old white-skinned female sustained a 44 per cent deep partial and full skin thickness burn due to petrol. She developed an invasive wound infection due to a fungus later identified as Curvularia species, an organism, usually a saprophyte, not previously reported as a cause of invasive burn wound infection. Treatment with surgical excision and Amphotericin B resulted in cure. PMID- 8435124 TI - Successful treatment of a severe electrical injury involving the stomach. AB - Apparently no report of the survival of a child with severe electrical injuries involving the stomach has been published. We successfully treated a 5-year-old boy with such injuries in August 1991. Our effective treatment included: (1) resection of the necrosis of the stomach immediately after admission; (2) active excision of all surrounding necrotic tissues with conservation of any piece of healthy tissue, including partial degenerative tissues; (3) early coverage of all exposed areas; (4) general comprehensive supportive therapy, and (5) local application of a saline solution containing chloromycetin and lidocaine. PMID- 8435125 TI - Iatrogenic bilateral femoral mycotic aneurysms: a case report following burns. AB - Haemodynamic monitoring is important in severely burned patients and repeated catheterization of the arteries of these victims seems to be inevitable. We present a 46-year-old female with 54 per cent TBSA burns who suffered from bilateral femoral mycotic aneurysms due to repeated arterial punctures. PMID- 8435126 TI - Upper airway obstruction--an unusual complication following a minor scalding injury. AB - A 14-month-old girl suffered a 10 per cent scalding injury from hot water of the type sometimes recognized as 'the teapot syndrome'. The hot water also reached the hypopharynx where it caused marked swelling of the mucosa and hence obstruction of the airway. Increasing respiratory distress made endotracheal intubation necessary 4.5 h after the accident. The girl was extubated 26 h later, and breathing was normal. The external burns were initially treated with baths and dressing changes. They healed mostly spontaneously, but four areas had to be grafted. This case report shows that thermal burns of the mouth and pharynx, followed by oedema and upper airway obstruction, can occur also in a minor scalding injury involving the face. Respiratory distress makes intubation necessary. PMID- 8435127 TI - Fluorescein and burn depth. PMID- 8435128 TI - [Sequelae of aging processes and/or disorders of the aged (2). Themes concerning nursing geriatric diagnosis]. PMID- 8435129 TI - [Analysis of a nursing problem (1). The nursing diagnosis: 2 steps]. PMID- 8435130 TI - [Analysis of a nursing problem (2). The nursing diagnosis: Mrs. Pratel]. PMID- 8435131 TI - [Who are the elderly? (1). Image formation about aging]. PMID- 8435132 TI - [The elderly and volunteer assistance (1). The volunteer assistance system: the couple P]. PMID- 8435133 TI - [The elderly and volunteer assistance (2). The volunteer assistance system: un unstable balance]. PMID- 8435134 TI - [The assessment scale: not waiting but doing]. PMID- 8435135 TI - [The geriatric nurse specialist in practice (1). The 5 functional areas]. PMID- 8435136 TI - [The geriatric nurse specialist in practice (2). Direct nursing care in the care for mentally handicapped]. PMID- 8435137 TI - [The geriatric nurse specialist in practice (3). Consultation on a GAAZ (Geriatric department of a general hospital)]. PMID- 8435138 TI - [Who are the elderly? (2). Self concept and subjective experience of aging]. PMID- 8435139 TI - [Sequelae of aging processes and/or disorders of the aged (1). The recognizability of the geriatric patient]. PMID- 8435140 TI - Neuromas of the facial nerve: a report of 12 cases. AB - Twelve patients with facial nerve neurinoma have been treated at The National Hospital, Queen Square, London, during the last 20 years. Nine tumours lay in the middle fossa arising from the area of the geniculate ganglion, two lay in the posterior fossa arising from the segment of the facial nerve in the internal auditory canal, and one tumour arose from the vertical segment of the facial nerve with extracranial extension through the stylomastoid foramen. Two patients had neurofibromatosis. The clinical and radiographic features of those tumours, the operative approaches employed, and the postoperative outcome are described. Complete tumour excision was achieved in all patients; all 12 remain free of recurrence 3-80 months after surgery. Facial nerve function was restored at least in part in all cases by transposition with end-to-end anastomosis, placement of a cable graft from the sural nerve or hypoglosso-facial anastomosis. The major determinant of the outcome of facial nerve function was the duration of preoperative facial paralysis, the results being invariably poor when this was of long duration. PMID- 8435141 TI - Temporal lobectomy for intractable epilepsy: experience with 58 cases over 21 years. AB - Sixty patients with intractable complex partial seizures underwent surgery between 1969 and 1990, and 58 of these underwent a temporal resection. Of 39 patients who had chronic subdural electrocorticography (ECoG) 37 subsequently underwent an anterior temporal lobectomy (ATL) and two had the electrodes removed without resection. Two patients had bilateral depth electrodes placed and then had an ATL. Fourteen patients with evidence of temporal structural lesions had temporal resections with intraoperative ECoG and five had resection without ECoG. Mean length of follow-up for all patients was 6 years. Fifty-five per cent of cases were seizure-free postoperatively, 7% almost seizure-free, 21% had worthwhile improvement and 17% no improvement. The outcome for patients with structural lesions was particularly good. Nine patients complained of mild memory impairment postoperatively and one had a severe amnestic problem. One patient with an unsuspected tumour developed a hemiparesis and dysphasia. One other patient had persistent dysphasia. No mortality was attributable to the surgery. It is concluded that ATL is an excellent operation for the treatment of intractable epilepsy arising from the temporal lobe and chronic subdural ECoG is a safe and reliable method for localizing the seizure origin. PMID- 8435142 TI - The laser in neurosurgery. PMID- 8435143 TI - First rib resection for the thoracic outlet syndrome. AB - Review of a personal series of 25 first rib resections for thoracic outlet syndrome shows that operation offers a 60% chance of improvement for an acceptable morbidity. This series is the first to consist solely of patients operated on for brachial plexus compression and diagnosed by stated criteria, which were: (1) pain and paraesthesiae running down the arm into the fingers (usually ulnar, but not exclusively); (2) reproduction of distal symptoms by pulling the shoulder down and back, and/or straight down, and/or forwards; (3) pressure in the supraclavicular fossa over the brachial plexus is painful and may reproduce the distal symptoms; and (4) a normal radiculogram. PMID- 8435144 TI - CSF shunting from the cisterna magna: a report of 16 cases. AB - Sixteen patients were treated with shunting of cerebrospinal fluid (CSF) from the cisterna magna for raised intracranial pressure (15 cases) or CSF leak (one case). There were 11 patients with benign intracranial hypertension, three with craniostenosis, one with chronic meningitis and one with a CSF leak. Cisternal shunting was effective in all cases and obviated the problems of low pressure and sciatica found with lumbar-peritoneal shunts. There were 11 revisions over a total of 31.5 shunt years (i.e. one per 2.9 shunt years). The role of cisternal shunting in neurosurgical practice is discussed. PMID- 8435145 TI - Stereotactic insertion of intracerebral electrodes in the investigation of epilepsy. AB - Intracerebral electroencephalography is sometimes necessary in the pre-surgical evaluation of patients with drug-resistant epilepsy, in order to define the site(s) of seizure onset. Accurate depth electrode insertion would ideally require multimodal image integration, repetitive and non-invasive localization, assessment of positional accuracy and freedom in target and entry point selection. A method for the acquisition of the multimodal image stereotactic information, necessary for the precise targeting of the mesial temporal structures, and the operative technique used for the accurate placement of the intracerebral electrodes is described. The use of the Gill-Thomas (G-T) stereotactic repeat localizer offers the degree of temporal freedom during the data acquisition period of the electrode implantation procedure which leads to the advantage of an unhurried multi-image integration and targeting in any individual case combined with less discomfort for the patient. The integration of the G-T repeat localizing system with the existing components of the Cosman Roberts-Wells (CRW-3) stereotactic system offers additional advantages. The target-centered arc-radius design allows complete freedom in the selection of the entry point, offers the possibility of multiple trajectories through the same entry point and permits a choice of either oblique or orthogonal lateral approaches, that are particularly useful for the electroencephalographic sampling of the posterior mesial temporal structures. The satisfactory localizing value of the technique and the additional advantage of easy confirmation of the positional accuracy of the electrodes during the postoperative period, using standard radiographic and magnetic resonance imaging studies, increases the potential of the technique for precise placement of depth electrodes during the pre-surgical evaluation of patients with epilepsy. PMID- 8435146 TI - The anterior interhemispheric trephine approach to anterior midline aneurysms: results of treatment in 72 consecutive patients. AB - We report the results of a prospective study of an anterior interhemispheric trephine approach in 72 consecutive patients with aneurysms of the anterior communicating artery (64 cases) and anterior cerebral arteries (eight cases). The salient features of the operative technique include a limited forehead crease incision, low anterior frontal midline trephine (4 cm), unilateral dural opening (2.5 cm), opening up of the anterior interhemispheric fissure and exposure of aneurysm and anterior cerebral vessels by a phased dissection. The best anatomical orientation is retained without compromising the superior sagittal sinus, falx cerebri, left frontal cortical veins, or eloquent areas of the brain. The results (excellent to good recovery or mild to moderate disability in 87.5% of cases) confirm that the technique is safe and well tolerated even in the elderly or fragile patients. PMID- 8435147 TI - Audit in the management of gliomas. AB - A retrospective study of 139 glioma patients was conducted in an effort to audit management. Factors affecting survival were studied using a Cox Proportional Hazard Model. These factors included age, sex, location, grade, type of surgery, use of radiotherapy, presenting symptoms, Karnofsky score on admission and Karnofsky score 3 months following surgery. Lower grade, high Karnofsky score on admission, radiotherapy and frontal location were associated with better survival. There was statistically insignificant evidence that the other factors had an influence on survival. Patients presenting with a poor neurological score were treated with burrhole biopsy alone. Only 10% of these patients survived more than 6 months. On the other hand, 26% of patients who had craniotomy on the basis of reasonable clinical status lived less than 6 months. Sixty-six per cent of patients in this craniotomy group were aged 60 years or over, and 66% of those aged over 60 had a Karnofsky score of less than 70. We conclude that careful judgement is required before subjecting patients aged over 60, especially those with a low Karnofsky score, to radical therapy. PMID- 8435148 TI - Peroperative vertebral arterial catheterization for proximal control in aneurysm surgery. AB - Peroperative balloon control of the proximal vessel can be used for a difficult basilar trunk aneurysm. A patient in whom this technique was used is presented and the exact radiological method is described. PMID- 8435149 TI - Raised intracranial pressure associated with hypercarbia after tourniquet release. AB - We report a case of acute raised intracranial pressure soon after deflation of arterial tourniquets in a patient with limb injuries as well as a severe head injury. The likely mechanism was release of carbon dioxide into the circulation as the ischaemic limbs were re-perfused. PMID- 8435150 TI - Spinal extradural cavernous angioma. AB - A case of spinal extradural cavernous angioma is described. The symptomatology and prognosis of such lesions is discussed and the relevant literature reviewed. PMID- 8435151 TI - Intraparenchymatous schwannoma of the cerebellum. AB - Intraparenchymatous schwannomas of the central nervous system are rare. In decreasing order of frequency they are found in the spinal cord, cerebral hemispheres, brainstem and cerebellum. So far, only six such tumours have been reported in the cerebellum. A male predominance and early onset of symptoms are salient features. A case of a 73-year-old Caucasian female with an intraparenchymatous schwannoma of the right cerebellar hemisphere which extended into the brainstem is reported. A complete cure followed surgical removal of the tumour. The preoperative clinical and radiological diagnosis was that of a cerebellar astrocytoma. PMID- 8435152 TI - Cerebellopontine angle medulloblastoma: case report and literature review. AB - The occurrence of cerebellopontine angle (CPA) medulloblastoma is a rare phenomenon. We report such a case in a 19-year-old girl who had 6th and 8th cranial nerve palsies as well as cerebellar dysfunction. The tumour arose from the left flocculus or adjacent cerebellar hemisphere and projected into the CPA. She was treated by subtotal removal of the tumour, followed by entire neuroaxis irradiation and immunochemotherapy. The clinical characteristics and pathogenesis of CPA medulloblastoma are reviewed and discussed. PMID- 8435153 TI - Simultaneous bilateral extradural haematoma. PMID- 8435154 TI - The impact of childhood cancer on 50 Chinese families. AB - As part of a larger study, a descriptive study of the impact of childhood cancer on 50 Chinese families was conducted in Guangzhou (Canton) in the Guangdong Province of the Peoples' Republic of China. The parents of children whose cancer was newly diagnosed (n = 25) or undergoing treatment (n = 25) were interviewed in Chinese and their responses were then translated to English. The children ranged in age from 3 to 16 years and had a variety of cancer diagnoses. Parental occupations and incomes varied. The majority (42%) of the families only had the child with cancer. The duration of symptoms before the diagnosis ranged from 1 week to greater than 2 years. Thirty-five parents (70%) believed that their child knew very little or nothing about their disease. The children learned of their diagnosis in a variety of ways. The parents varied in their degree of openness regarding the child's diagnosis with relatives, friends, and colleagues. Some families had previous experience with a serious illness or death, but all identified cancer as the most frightening disease. Forty-one percent of the families felt they had not adjusted yet to the diagnosis. Few acknowledged the impact on siblings. Families also described their outlook on life and their fears of death. Seventy-six percent of the families were paying the total cost of their child's care themselves, and 14% of the total number of families reported major financial problems. PMID- 8435155 TI - The phenomenon of hand holding as a coping strategy in adolescents experiencing treatment-related pain. AB - The purpose of this study was to understand the phenomenon of hand holding as a coping strategy used by adolescents to deal with treatment-related pain. The convenience sample consisted of 20 adolescents whose ages were 11 to 19 years: 10 had cancer and 10 had renal disease (this served as the comparison group). Using a descriptive design, a semistructured interview was conducted with each adolescent. To supplement and support interview data, structured observations were conducted as adolescents underwent painful treatments (eg, blood draws, shunt placement, peripheral chemotherapy, lumbar punctures, and bone marrow aspirations). Data were analyzed using descriptive statistics and qualitative analytic techniques similar to those delineated by Strauss and Corbin. The results of this study indicated that subjects in both the cancer and the renal disease group perceived hand holding to be a very effective coping strategy in ameliorating treatment-related pain. Overwhelmingly the patients preferred to hold their mother's hand. When the mother was unavailable, they preferred to hold a specific nurse's hand. Hand holding functioned to reduce tension associated with impending treatments, as a source of distraction, and as a source of security. Accordingly, adolescents' subjective experience of treatment-related pain was reduced when they felt more secure, less tense, and were distracted. PMID- 8435156 TI - Orem's theory used as a guide for the nursing care of an eight-year-old child with leukemia. AB - Orem's general theory of nursing provides a framework for holistic pediatric oncology nursing. In this article, an overview of Orem's theory is provided. The theory is used to assess the self-care deficits of an 8-year-old boy who has been diagnosed with leukemia, the ability of the mother to meet the son's self-care demands, and the nursing system needed to assist the mother to meet her son's self-care demands. The theory is used to plan and evaluate the nursing care of this child. A comprehensive list of nursing diagnoses and a nursing care plan for two of these diagnoses are presented. PMID- 8435157 TI - Long distance related stressors and coping behaviors in parents of children with cancer. AB - This descriptive comparative study addresses long distance related stress and coping behaviors of 53 parents of children with cancer. The purpose of the study was to determine the differences in the stress and coping behaviors of parents living 100 miles from the tertiary treatment center compared with those who live less than 100 miles from the center. The theoretical framework used was Lazarus' theory on stress and coping. The study participants were from several Pediatric Oncology Group member institutions. The parents completed Hymovich's Parent Perception Inventory and a demographic data sheet. Parametric (one-tailed t-test) and nonparametric (Mann-Whitney and chi-squared tests) were included in the statistical analysis. The results showed significant differences in demographic data, concerns, beliefs/feelings, and coping. Implications for the pediatric oncology treatment team include specific interventions that will improve the quality of care for the children/parents who live a long distance from the tertiary treatment center. PMID- 8435158 TI - Searching the literature creatively: updating your skills in reviewing the literature. AB - Reviewing the literature is not only an essential aspect of research, it can be a creative process. Computerized searches decrease the hours that searches formerly took and allow the researcher to link concepts in ways that were previously difficult to do. Be consistent with your approach to reviewing the literature and your reward will be a comprehensive overview of the extant literature--an excellent start to validating your research project. PMID- 8435159 TI - [Wasted years--politics and the promille limit]. AB - Already as early as 1955 the German Federal Board of Health pointed out that the legal treatment of drunken drivers according to traffic (criminal) law regulations was not in accord with the proven effects of alcohol upon the human system and traffic safety. The Board of Health therefore recommended a revision of the regulation. The acceptable percent of alcohol in the blood of a driver should not exceed 0.08% while the said person is operating a motorized vehicle. Further, if a driver is found to be over the limit, he will be punished by law. This author has shown the extent to which policymakers have gone in attempting to pass laws which concur with recommendations resulting from scientific/medical research. Regarding this issue, it is especially disturbing that little attempt has been made to assimilate East German law into West German law. PMID- 8435160 TI - ["Drinking and driving" with various blood alcohol limit values in Europe]. AB - Within the framework of a comparative cross-national study led by INRETS, France, in 1991/92, representative surveys of drivers were conducted in 15 European countries. The survey covered a wide spectrum of biographical driver data as well as opinions and attitudes to practically all subjects of road traffic. In this context, the "drinking and driving" subject was of special interest. A comparison was made between drivers from 10 countries with a legal BAC limit of 0.08% and drivers from 5 countries with a legal BAC limit of or under 0.05%. Drivers from countries with a legal BAC limit below 0.08% state more often that they never drive after drinking even a small amount of alcohol; have been stopped and breathalysed by the police on at least one occasion; expect to be stopped and breathalysed by the police on a typical journey. They further advocate more breath tests by the police in their country and harsher penalties for drivers found to be over the limit. Where low legal BAC limits are in force, they are accepted in most cases. The extent to which these basically positive attitudes may also be relevant on the traffic scene, cannot be answered based on this survey alone. It is common knowledge that opinions and attitudes represent only one determining factor of a whole complex of factors influencing behaviour. PMID- 8435161 TI - [Women and drunk driving--references from the legal expert practice]. AB - From 1980 to 1990 the number of female drunken drivers increases significantly from 5.33% to 7.87% in Germany. Women between 25 and 55 years old are overrepresented, especially the 35-45 aged. The number of women, who had been sentenced for the first time because of drunken driving significantly decreases from 12.75% in 1985 to 9.07% in 1990 within the total subpopulation of those who were medical-psychologically examined in Munster. The blood-alcohol concentrations (BACs) of the women examined in Munster were analyzed. There were no differences in the average BACs and in the variance. In every year the examined women were part of the same population of people with similar problems. The average BACs are 2.04/1000 (1980), 2.2/1000 (1985) and 2.01/1000 (1990). The analysis of the results of the medical-psychological examinations shows no significant difference between men and women in 1990. In 1980, 1985 and 1990 there was no increase in negative judgements because of medical reasons, in 1980 only one woman was suggested to participate in a driver-improvement-course and in 1985 significantly less women were rejected because of psychological reasons. This was caused by a significant increase in positive judgements in the subgroup of those women, who had more than one drunken driving offence or other incidents. The results show, that those women examined in Munster belong to the group of people who drink alcohol in an excessive an abnormal way. The equal treatment of women and men by the examining psychologists can be regarded as justified. In respect to the different conditional structure responsible for abnormal drinking of women in comparison to men it is necessary to examine women and men in different ways. PMID- 8435162 TI - [Blood methanol as a marker of alcoholism. A diagnostic component within the scope of expert assessment of driving competence in alcoholic intoxication]. AB - A blood methanol test which was done in addition to routine diagnosis of the blood methanol level of persons with alcohol driving delicts in the past who were alcoholized during the medical-psychological investigation (MPU) produced differently significant cues for (pre) alcoholism in nearly all persons. As a result 15 out of 40 persons reached a blood methanol level of 10 mg% and more (24 more persons a level between 1.5 and 9.9 mg%). This is a clear indicator of pathological alcohol drinking. Persons with a breath alcohol concentration from 0.2 to 0.99/1000 showed an average blood ethanol concentration of less than 10 mg%, but above 1.5 mg%, where as those persons with an alcohol level above this limit had a blood methanol concentration significantly above 10 mg%. The arithmetical mean and the standard deviation were significantly elevated compared to the range of reference, an effect that didn't show as clearly with the median of the Gamma-glutamyltransferase (GGT). The mean corpuscular volume of erythrocytes (MCV) reacted less sensitively. The correlation between the five parametres (blood ethanol at the last alcohol driving delict, breath alcohol concentration, GGT, MCV, blood methanol) were all significantly positive with one exception: the correlation between the breath alcohol and the blood methanol level. Altogether the results support the hypotheses that the protective assertions of the subjects concerned are hard to believe, even those of persons with a lower blood alcohol level. An additional test of the blood methanol level should be done, however, with persons reaching an alcoholization between 0.2 and 1.0/1000 during the MPU.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8435163 TI - Clinical behavior of acoustic tumors. A flow cytometric analysis. AB - OBJECTIVE: Recently, nonsurgical treatment of acoustic tumors has been advocated as an alternative to surgical resection. Because of the relatively short follow up in reported series of radiation-treated acoustic tumors, the lack of growth of some tumors may merely reflect the variable biologic growth potential of these tumors and not the result of treatment. DNA flow cytometry has been used to predict biologic activity in other solid tumors. It is applied in this study to assess the variability of growth potential in a typical acoustic tumor population and to determine whether relationships exist between flow cytometric data and clinical characteristics of acoustic tumors. DESIGN: DNA flow cytometry techniques were used to evaluate formalin-fixed, paraffin-embedded tissue previously obtained from patients who were surgically treated for acoustic neuromas. Relationships between flow cytometry data and historical data were also statistically evaluated. SETTING: Tissue samples were from patients of a large private otologic practice. PATIENTS: Subjects were a convenience sample of 49 patients (26 female and 23 male) with a mean age of 59 years who had undergone surgical removal of an acoustic neuroma. None of the patients had other stigmata of neurofibromatosis or tumor recurrence. All tissue specimens were pathologically confirmed acoustic neurons, with a range in tumor size from 1 to 6 cm. MAIN OUTCOME MEASURES: The measures included DNA ploidy and S-phase fraction. Historical data included age, sex, size of tumor, presenting symptom, and symptom duration. RESULTS: All 49 tumors showed a diploid distribution, with S-phase values ranging from 1.07% to 20.74% (mean +/- SD, 6.30 +/- 4.24). The ploidy and S-phase data compare favorably with previously published data in which fresh tissue was used. There were no statistically significant relationships between S phase value and historical data. CONCLUSIONS: The wide range of S-phase values is consistent with a large variation in tumor growth potential and suggests caution in interpreting the results of radiation treatment of acoustic tumors when follow up relatively short. PMID- 8435164 TI - Morphologic development of experimental cholesteatoma. AB - Using light microscopy, we studied the morphologic events of cholesteatoma progression 8 months after ligation of the ear canal in 14 Mongolian gerbils. Although we observed a wide range of progression, four stages of morphologic development could be clearly distinguished among the 28 specimens: stage I, an orthokeratotic plug in the ear canal without tympanic membrane involvement; stage II, partial retraction of the tympanic membrane; stage III, the interface between cholesteatoma encapsulated within the tympanic membrane and mucosal membranes covering the promontorial wall of the middle-ear cavity was characterized by a buildup of granulation tissue with prominent macrophage infiltration; and stage IV, bone destruction. Chronic inflammation was observed in some but not all stage II to IV cases. Our results indicate that hyperkeratosis is a primary event in cholesteatoma development, that the development of the granulation tissue with activated macrophages may be responsible for the bone destruction, and that acute or chronic inflammation is not a prerequisite for the development of cholesteatoma or the bone resorptive process. PMID- 8435165 TI - External and middle ear status related to evoked otoacoustic emission in neonates. AB - OBJECTIVE: Screening auditory status prior to neonatal hospital discharge to identify newborns with severe hearing impairment is an important pediatric care priority. Evoked otoacoustic emission (OAE) testing is a quick noninvasive method. The purpose of this study was to determine the relationship between external auditory canal and middle ear status with click-evoked OAE. It was hypothesized that vernix caseosa, debris in the ear canal, and middle ear fluid contribute to the OAE fail rate. DESIGN: All neonates had an initial OAE examination. A second investigator, "blinded" to the results, examined all ears otoscopically, cleaned any obstructing debris, and repeated with a second OAE test. SETTING: All neonates were tested in a designated nursery at a mean age of 43 +/- 21 hours. PATIENTS: Forty-one full-term neonates were prospectively enrolled. INTERVENTION: The ear canals with debris were cleaned under direct vision with a pediatric swab dampened by an alcohol wipe. OUTCOME MEASURE: The primary outcome measure was the postcleaning OAE pass rate. RESULTS: The preotoscopic examination pass rate of 82 ears was 76%. The OAE pass rate improved to 91% after debris removal. CONCLUSIONS: The results indicate that the examination and cleaning of the external ear canal are important components of the neonatal screening process. PMID- 8435166 TI - Effects of inhalant anesthesia on the middle ear as measured by tympanometry. AB - This investigation examined the effects of inhalant anesthesia, nitrous oxide and halothane, on middle ear pressure. Moreover, the effect of inhalant anesthesia on the validation procedure for tympanometry was examined. Tympanometry was used to measure middle ear pressure variations. Subjects were examined with tympanometry prior to and after the administration of inhalant anesthesia. Group 1 (N = 86) received halothane and nitrous oxide. Group 2 (N = 52) received halothane only. Group 1 data were gathered in a previous investigation. The investigation was continued with subjects in group 2. Results indicated that middle ear status prior to anesthesia was not significantly different from middle ear status under anesthesia. In addition, middle ear pressure changes due to nitrous oxide were not significantly different from middle ear pressure changes due to halothane alone. Moreover, there was no effect on the tympanometry validation procedure. These findings are consistent with previous studies that indicate nonsignificant changes in middle ear pressure associated with the use of nitrous oxide and halothane. PMID- 8435167 TI - Clinical scoring system in the evaluation of adult pharyngitis. AB - OBJECTIVE: To compare results of a clinical scoring system for diagnosis of group A streptococcal pharyngitis with microbiologic results, when several different pharyngeal pathogens were tested simultaneously. DESIGN: Evaluation of clinical manifestations of 106 adult patients with pharyngitis of different microbial origin. SETTING: General private practice; Health Center Pulssi, Turku, Finland. PATIENTS: Adult patients whose chief complaints were sore throats. MAIN OUTCOME MEASURE: A symptom score that was assigned to each patient according to the total number of certain signs and symptoms that are postulated to increase the probability of group A streptococcal pharyngitis and blood measurements for infection. RESULTS: The highest symptom scores, 3 and 4, were found in 21 patients. These patients had pharyngitis due to group A streptococcus (four patients), group C streptococcus (four patients), group G streptococcus (two patients), group F streptococcus, Mycoplasma pneumoniae, Chlamydia pneumoniae, influenza A virus, influenza B virus, herpes simplex type 1 virus (two patients), and coxsackie B4 virus. No pathogen could be identified from three of the 21 patients. The C-reactive protein values and the leukocyte counts were raised significantly more often in streptococcal infections than in infections of other origin; the P values were .00016 and .028, respectively. CONCLUSION: Use of a clinical scoring system alone for diagnosis of pharyngitis may lead to improper use of anti-microbial agents. There is a need for accurate microbiologic diagnostic procedures in general practice to determine proper treatment of pharyngitis as well as to test the effect of antibacterial and, in the future, antiviral treatment in respiratory tract infections. PMID- 8435168 TI - Control of early postoperative pain with bupivacaine in adult local tonsillectomy. AB - Early postoperative pain following tonsillectomy remains a significant obstacle to speedy recovery and smooth convalescence. Inadequate analgesia causes poor oral intake and occasionally requires overnight hospitalization in same-day surgery practices. Although several otolaryngologists anecdotally support intraoperative infiltration with long-acting anesthetic agents for postoperative pain control, to our knowledge, no previous study confirms this claim. In a prior investigation, we found no difference between bupivacaine hydrochloride and saline placebo in pediatric patients undergoing tonsillectomy. In this trial, we performed a similar study in an adult population. Fifty-one patients undergoing tonsillectomy with local anesthesia were randomized into bupivacaine or saline placebo groups. Patients provided the following data: (1) pain level; (2) oral intake; (3) number of pain medication doses; and (4) level of pain on jaw opening, all at 10 hours postoperatively. Bupivacaine administration resulted in no adverse effects. No difference was noted in pain level, amount of oral intake, or pain on full jaw opening. Bupivacaine group patients received fewer though not statistically significant doses of pain medication than placebo group patients. We conclude that bupivacaine is a safe medication but offers no advantage in the control of early postoperative pain in adult patients undergoing local tonsillectomy. PMID- 8435169 TI - Lag screw fixation in the upper craniomaxillofacial skeleton. AB - Rigid internal fixation of the craniomaxillofacial skeleton has become commonplace in osseous reconstructive procedures of the face. While miniplates are useful in many traumatic, reconstructive, and congenital anomaly cases, they are often unnecessary. Lag screw fixation is routinely used in the mandible and has the advantage of maximal stability when compared with other fixation techniques. These principles can similarly be applied in a variety of situations in the upper facial skeleton, including fracture and bone graft fixation, as well as in pediatric craniofacial surgery. We review the technique and appropriate indications and demonstrate via case examples this diversity of applicability for using lag screw techniques. Finally, results of 83 cases in which this technique has been used will be reviewed, including complications. PMID- 8435170 TI - Comparative postoperative infection rates in midfacial trauma using intermaxillary fixation, wire fixation, and rigid internal fixation implants. AB - The use of rigid internal fixation implants in the repair of midfacial fractures requires more extensive bone exposure, soft-tissue manipulation, and operative time. We wished to determine the relative contribution of this method of repair to postoperative infection rates. Midfacial trauma cases occurring between the years 1984 and 1991 at the University of Iowa Hospitals and Clinics, Iowa City, were reviewed. Patients were grouped according to method of repair (intermaxillary fixation, open reduction with wire fixation, or open reduction with rigid internal fixation plates). Postoperative infection data (wound infections, sinusitis, etc) were obtained by chart review and telephone interview. Minimum follow-up for inclusion in the study was 3 months, with an average follow-up for all groups of 28.8 months. We found no significant difference in the rate, or the type, of postoperative infections in all three groups. We conclude that rigid internal fixation implants do not contribute increased postoperative infection rates in midfacial trauma. PMID- 8435171 TI - Pharmacologic and surgical enhancement of composite graft survival. AB - A previously described rabbit ear model was used to address the following issues: (1) the role of surgical delay in composite tissue transfer, (2) optimal enhancement of graft survival using the corticosteroid methylprednisolone, (3) pharmacologic salvage of the failing composite graft, and (4) efficacy of a nonsteroidal dual cyclooxygenase/lipooxygenase inhibitor (SK&F 86002) in enhancing graft survival. Preoperative and immediate postoperative steroid treatment groups exhibited a significant improvement in graft survival area compared with the untreated control group. Preoperative initiation of steroid therapy was more effective than a strictly postoperative regimen. SK&F 86002, advance preparation of the recipient bed, and delayed steroid administration did not improve graft survival compared with the untreated control group. The most promising treatment, preoperative initiation of steroid therapy, was further evaluated in a double-blinded placebo-controlled study. The steroid group demonstrated a significantly improved mean survival area, as well as mean graft weight, compared with the placebo control group. PMID- 8435172 TI - Endoscopic assessment in children with tracheotomies. AB - Pediatric tracheotomy is a safe procedure, and the tube can be maintained for a prolonged period. There are, however, few guidelines regarding the endoscopic assessment of the airway following tracheotomy. From January 1988 through December 1989, the Division of Otolaryngology of The Children's Hospital of Philadelphia (Pa) performed tracheotomies on 81 patients. Thirty-two children had direct laryngoscopy and bronchoscopy at the time of the procedure, 1 week later, and at 6-month intervals for a minimum of 18 months. Four children had normal airways while 21 had intraluminal stomal granulomas, 16 had development of subglottic stenosis, nine had collapse of the anterior tracheal wall, and three had development of distal tracheal granulations. Sixteen children had multiple lesions. Anatomic changes occur in the airways of the majority of children with long-term tracheotomies, and endoscopic evaluation is an essential part of their care. PMID- 8435173 TI - Dermal metastases in epidermoid carcinoma of the head and neck. AB - Many studies have reported on the incidence and location of metastases from squamous cell carcinoma of the head and neck; these studies rarely comment on the incidence of cutaneous metastases. Several studies have analyzed dermal metastases from all carcinomas. Specific issues pertaining to dermal metastases from head and neck carcinomas remain poorly defined. An extensive literature review was performed, and information on similar patients followed up at our institutions was compiled in an attempt to further identify the characteristics of this unique group. Speculation on the mechanisms of these metastases is included. PMID- 8435174 TI - Bilateral aberrant internal carotid artery case presentation. AB - Cases of aberrant internal carotid artery in the middle ear have been well documented. However, bilateral aberrant intratympanic carotid artery presentation, as in this case, is quite rare. In addition, in this case, there was unilateral duplication of the cervical and petrous portions of one internal carotid artery such that the duplicated portion rejoined the normal internal carotid artery in its petrous portion. The purpose of this article is to review the literature regarding aberrant internal carotid artery presentation in the middle ear and to discuss the related embryological and anatomical features as well as diagnosis of this lesion, using a unique case as an example. PMID- 8435175 TI - Anticus-lateralis muscle suturing. Treatment of recurrent nerve paralysis. AB - We have devised a new surgical method that sutures the cricothyroid (anticus) muscle to the paralyzed lateral cricoarytenoid (lateralis) muscle for the dynamic reconstruction of the larynx. Because this method achieved remobilization of the paralyzed vocal cord in dogs, we applied it to seven patients with unilateral recurrent laryngeal nerve paralysis (four patients had postsurgical paralysis and three patients had idiopathic paralysis). We obtained the following satisfactory results: (1) vocal cord tension and voice quality improved in all patients, and (2) in four patients, remobilization of the paralyzed vocal cord was obtained. We believe that this surgical method could serve as a new dynamic method of reconstruction for the treatment of unilateral recurrent laryngeal nerve paralysis. PMID- 8435176 TI - Autoimmune exocrinopathy presenting as recurrent parotitis of childhood. AB - OBJECTIVE: To describe a case of autoimmune exocrinopathy in a child at the age of 3 months who presented with the original diagnosis of recurrent parotitis. DESIGN: This a case report of a 9-year-old girl with recurrent parotitis who was later found to have Sjogren's syndrome. The literature relating to primary Sjogren's syndrome in the pediatric population is reviewed. SETTING: The patient was seen in the rheumatology and otolaryngology clinics at a university medical center. INTERVENTIONS: This study did not address therapy. MAIN OUTCOME MEASURE: Diagnosis of Sjogren's syndrome. RESULTS: The patient had xerostomia, an abnormal result of a salivary gland biopsy, SSA and SSB antibodies, and the histocompatibility antigens HLA-B8 and HLA-DR3 that are associated with Sjogren's syndrome. CONCLUSION: Primary Sjogren's syndrome should be considered in cases of recurrent parotitis of childhood. More studies are needed to assess the natural history of autoimmune exocrinopathy in children. PMID- 8435177 TI - Pathologic quiz case 2. Paraganglioma of the larynx. PMID- 8435178 TI - Pathologic quiz case 1. Adult rhabdomyoma of the parapharyngeal space. PMID- 8435180 TI - Percutaneous coronary angioscopy: present role and future direction. PMID- 8435179 TI - Recurrent tonsillitis: the role of Chlamydia and Mycoplasma. PMID- 8435181 TI - Human gene mutations affecting RNA processing and translation. AB - Gene mutations affecting mRNA processing and translation are not common causes of human genetic disease. Their analysis has nevertheless provided important insights into the basic biochemical mechanisms underlying mRNA transcription and translation. PMID- 8435182 TI - Essential drugs. AB - Availability of an appropriate selection and regular supply of affordable drugs that are efficacious, safe and of good quality, is a prerequisite for any operative health care system. In most of the industrialized countries a variety of drugs are usually available in sufficient quantity and some drugs may even be over-used in medical therapy, yet half the world's population lacks regular access to the most needed drugs. This article describes some activities the World Health Organization (WHO) has undertaken since 1977 in order to determine and publish an updated model list of essential drugs and to safeguard everyone's equitable access to the most needed drugs. PMID- 8435183 TI - Colony-stimulating factors: a new step in clinical practice. Part II. AB - Clinical application of colony-stimulating factors (CSFs) such as recombinant human granulocyte colony-stimulating factor (rhG-CSF) and recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) are advancing rapidly now that these factors are approved as indicated therapy in patients with chemotherapy-induced neutropenia, patients undergoing autologous bone marrow transplantation (BMT) and patients who develop graft failure after BMT. Novel CSFs are also being explored for potential clinical application in situations not as significantly affected by rhG-CSF or rhGM-CSF. Studies determining unique effects of novel factors, combinations of factors and combinations with peripheral blood progenitor cell fusions which may lead to future clinical applications of CSFs will be reviewed. PMID- 8435184 TI - Surgeon's dilemma: in situ carcinoma of the female breast with special reference to limited surgery. PMID- 8435185 TI - Disorders of blood viscosity. AB - In clinical situations associated with disturbed blood flow, the primary focus is usually on improving cardiovascular performance. However, during recent decades, both basic science and clinical literature reports have presented evidence that the flow properties of blood must also be considered in these situations. Thus, the relatively new fields of haemorheology and clinical haemorheology have evolved; the former deals with the flow and deformation behaviour of blood, plasma and the formed elements of blood, whereas the latter relates to alterations of their behaviour in various pathophysiologic states. This review therefore summarizes some of the salient aspects of clinical haemorheology and of the determinants of blood flow properties (flow rate, haematocrit, plasma viscosity, red cell aggregation, red cell deformability). In addition, it briefly describes several clinical disorders associated with abnormal blood, plasma or cell rheology ('hyperviscosity syndromes' occurring in polycythaemia, leukaemia, sickle cell disease, paraproteinaemias). PMID- 8435186 TI - Efficacy of gemfibrozil in dyslipidaemic subjects with suspected heart disease. An ancillary study in the Helsinki Heart Study frame population. AB - During screening in the Helsinki Heart Study (HHS), a 5-year coronary primary prevention trial with gemfibrozil, some 600 dyslipidaemic individuals were detected who exhibited symptoms and signs of possible coronary heart disease (CHD). These subjects were excluded from the primary study. To secure successful conduct in the HSS, an ancillary protocol was developed for the treatment of these individuals. Three-hundred and eleven subjects were randomized to receive gemfibrozil 600 mg twice daily and 317 subjects to receive a matching placebo over 5 years in a double-blind fashion. The end-point rate, consisting of fatal and non-fatal myocardial infarction and cardiac death, did not differ significantly between the placebo and gemfibrozil groups. The same was true for total mortality. Missing key prognostic factors, e.g. true prevalence of CHD, extent of coronary artery obstructions, degree of left ventricular dysfunction, and their distribution in the groups render the results less reliable and hence the data cannot be used to refute the thesis that treatment of dyslipidaemia in manifest CHD in successful. PMID- 8435187 TI - Dilemmas of public sector contraceptive development. PMID- 8435188 TI - Assisted suicide and euthanasia: experiences from The Netherlands. PMID- 8435189 TI - Trends in population and contraception. AB - There has been an explosion in contraceptive use in the past 30 years. In 1960 65, the level of contraceptive use in the developing countries of Asia, Latin America and Africa represented about 9% of married couples of reproductive age. In the 1990s use of contraception in developing countries comprises over 50% of couples and contraceptive prevalence is increasing each year. Total fertility rates for the developing world have already fallen from over 6, where they were in 1960 to about 4, halfway toward the replacement level of 2.1. The United Nations projects that during this decade, over 90 million people will be added each year to world population. If this projection is not to be exceeded, prodigious supplies of contraceptives will have to be available at affordable cost to the people of developing countries, where 94% of this population increase will occur. New technology alone will not guarantee this success, but it would help ensure that people are able to meet their fertility objectives. PMID- 8435190 TI - Study and introduction of family planning methods in developing countries. AB - Research in developing countries is essential for the evaluation of the safety, efficacy and acceptability of both new and already available contraceptives. Research conducted by scientists in developing countries has also played an essential role in the development of new contraceptives. The continuous delivery of progestin at a low dose, copper IUDs, contraceptive implants, monthly injectables and vaginal rings are examples of new methods developed with the input of research conducted largely in developing countries. When research in developing countries is funded or coordinated by international agencies, local scientists have to be involved not only in its implementation, but in the planning, analysis and dissemination of such research. The World Health Organization, the Population Council and Family Health International have played an important role in supporting collaborative studies for the development, introduction and evaluation of family planning methods in developing countries. PMID- 8435191 TI - Mode of action of RU 486. AB - RU 486 is a 19-norsteroid which has a specific high affinity binding to the progesterone and glucocorticoid receptor. It is generally accepted that RU 486 acts as a pure progesterone antagonist almost without agonistic activity. RU 486 acts mainly directly on the target organ, such as the endometrium, but also to some extent indirectly through an effect on the pituitary gonadotrophin secretion. The effect of RU 486 during the menstrual cycle is dependent on time of treatment. Treatment before ovulation will result in a prolongation of the proliferative phase of the menstrual cycle, while treatment during the mid- and late luteal phase will invariably induce bleeding, often followed by a second bleeding episode at the expected time of menstruation. The only treatment period which does not influence the menstrual cycle is treatment immediately following ovulation. Treatment during the proliferative phase has no effect on endometrial morphology but inhibits follicular development and delays oestrogen and LH surge. Treatment on the first days following ovulation has no effect on ovarian steroid concentration, but will significantly delay endometrial development, cause a change in the concentration of oestrogen and progesterone receptor concentration enzyme activity and production of substances thought to be progesterone dependent. The change in endometrial development is sufficient to prevent implantation. In mid- and late luteal phase, treatment with RU 486 will result in endometrial shedding in spite of normal progesterone levels. Post-ovulatory treatment with RU 486 will also significantly change uterine contractility. In early pregnancy, withdrawal of progesterone inhibition will result in uterine contractility and a significant increase in the sensitivity of the myometrium to prostaglandin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8435192 TI - Clinical use of mifepristone (RU 486). AB - Because progesterone is essential for the establishment and maintenance of pregnancy, it has long been recognized that a substance which antagonized the action of progesterone would have potential as an antifertility agent. Within 2 years of the synthesis of the progesterone antagonist RU 486 (mifepristone) it was demonstrated that bleeding and uterine contractions occurred following its administration in non-pregnant and pregnant women. Extensive trials over the last 10 years have established that a single dose of mifepristone followed 36-48 hours later by a prostaglandin, is an effective, safe alternative to vacuum aspiration for the termination of early pregnancy. Although this combination is licensed in France, China and the United Kingdom for induction of abortion, research is continuing to determine the minimum effective dose of mifepristone and type of prostaglandin which is associated with minimum side effects without loss of efficacy. In addition, studies to determine the acceptability of this type of medical abortion to women in different cultures and societies are required. The facilities necessary for medical termination differ from those for surgical abortion, although the requirements for access to emergency resuscitation and treatment of (rare) complications are similar for the two methods. Mifepristone is very effective in the management of prostaglandin-induced midtrimester abortion. By sensitizing the uterus to prostaglandin, the dose of prostaglandin can be reduced with a shortened prostaglandin-abortion interval. Administration of mifepristone in the early luteal phase of the cycle delays the development of a secretory endometrium. Preliminary studies suggest that it may be highly effective when given at this time as a post-coital contraceptive or 'once a month' pill. Although antigestagens offer great promise as agents to help regulate human fertility, their widespread use may be constrained more by religious and political factors, rather than by demonstration of clinical efficacy. PMID- 8435193 TI - Percutaneous and transdermal oestrogen replacement therapy. AB - The benefits of oestrogen replacement therapy (ERT) have been widely recognized. However, among the drawbacks ascribed to ERT, metabolic disturbances have been observed, particularly after oral administration of oestrogens. Therefore, other routes of delivering oestrogens have been developed. The advantages of delivering drugs through the skin for systemic therapy have been widely recognized and represent a growing sector in drug development. Transdermal delivery of steroids is also a rapidly expanding field and in various clinical situations where hormonal replacement therapy is needed this route of administration is a real breakthrough, considering the relative toxicity of some steroids when given orally. Percutaneous application of steroids has been proven successful in various disorders. Various occlusive transdermal systems have also been designed, all of them aimed at achieving a constant release rate of the molecules contained in their reservoir through the intact skin. The skin itself, and especially the outermost layer, the stratum corneum, can play the role of a reservoir and a rate controlling membrane. In the field of reproductive hormones, so far, oestradiol, progesterone and testosterone have been demonstrated to be good candidates for transdermal delivery. The effectiveness and the acceptability of transdermal delivery of oestradiol in postmenopausal women have been demonstrated. All the beneficial effects of oestrogen therapy can be achieved through skin delivery, e.g. symptoms relief as well as osteoporosis prevention. PMID- 8435194 TI - Androgen receptor and mechanism of androgen action. AB - Androgen receptor is the intracellular protein that mediates biological actions of physiological androgens (testosterone and 5 alpha-dihydrotestosterone). Androgen receptor belongs to a large family of ligand-dependent proteins whose function is to modulate expression of genes and gene networks in a cell- and tissue-specific manner. The present overview describes the structurally important domains of the receptor protein, and discusses several aspects in the structure function relationship, using naturally occurring receptor mutants in androgen insensitivity patients or experimental animals as examples. In addition, characteristics of androgen receptor expressed in a heterologous system are described, and their potential usefulness in specific molecular studies discussed. PMID- 8435195 TI - Serum tumour markers in lung cancer. PMID- 8435196 TI - Breast cancer and osteoporosis--a bridge at last. PMID- 8435197 TI - High-dose chemotherapy with autologous bone marrow rescue in advanced stage IV neuroblastoma. AB - In order to better evaluate the role of bone marrow purging procedures in the treatment of stage IV neuroblastoma, two similar groups of patients, prospectively treated during the same period at Leon Berard Center, Lyon, France, and at Giannina Gaslini Institute, Genova, Italy, were reviewed. 18 children were treated in Lyon with a protocol including induction chemotherapy, surgery and a single course of high-dose chemotherapy followed by purged autologous bone marrow rescue. 21 patients were treated in Genoa with a very similar protocol which did not include purging procedures. Progression-free survival at 6 years was 12% (95% confidence interval 0-24%), without any difference between the two series of patients. The only prognostic factor for long-term survival was the persistence (or not) of bone lesions and the presence of metastatic disease (bone or bone marrow) at graft. The small numbers in the two groups and the very poor outcome make it difficult to conclude on the efficacy of purging. PMID- 8435198 TI - Plasma insulin-like growth factor-1 (IGF-1) concentrations in human breast cancer. AB - Insulin-like growth factor-1 (IGF-1) is capable of stimulating breast cancer cell growth in vitro and the presence of IGF-1 receptors has been demonstrated in primary breast cancers. We determined plasma IGF-1 in a primary breast cancer population and in a control population. Radioimmunoassays were performed either directly on plasma, IGF-1 (NE), or after an acid-ethanol extraction of the plasma, IGF-1 (E). We demonstrated an inverse correlation between age and IGF-1: for this reason, only results obtained in females of the same age range (> 35 years) were compared. Median concentrations of IGF-1 were significantly higher in primary breast cancers [IGF-1 (E) = 152 ng/ml, IGF-1 (NE) = 26 ng/ml, n = 44] than in controls [IGF-1 (E) = 115 ng/ml, IGF-1 (NE) = 20 ng/ml, n = 92]. To our knowledge such a growth factor increase has never been described in breast cancer. We conclude that IGF-1 could be an important factor involved in the development of breast cancer and that treatment reducing IGF-1 levels could be beneficial for patients. PMID- 8435199 TI - Oestrogenic effects of adjuvant tamoxifen in postmenopausal breast cancer. AB - Oestrogenic influence of the non-steroidal anti-oestrogen tamoxifen may have consequences for the morbidity pattern among women on long-term adjuvant treatment. Subclinical oestrogenic effects of adjuvant tamoxifen on the tissue level was studied among 16 postmenopausal women in three different organ systems: the pituitary, the liver and bone. After 3 months of adjuvant tamoxifen prolactin levels decreased 66% (P < 0.001) in comparison with pretreatment levels. There was an 80% increase in basal growth hormone after 3 months of treatment in comparison with pretreatment levels, which did not reach statistical significance (P = 0.07). Sex hormone binding globulin levels increased 39% (P < 0.01) and IGF 1 (somatomedin C) levels decreased 20% (P < 0.05). The levels of bone GLA protein (BGP; osteocalcin), a marker of bone osteoblastic activity, decreased 28% (P < 0.01). In 13 of the patients bone mineral density (BMD) was measured before treatment and after 1 year. No significant change in BMD was observed. The results thus suggest a clear oestrogenic effect of tamoxifen on the pituitary, liver and bone in postmenopausal women. PMID- 8435200 TI - The effect of differing radiotherapeutic schedules on the response of glottic carcinoma of the larynx. AB - Laryngeal tumours, especially T1N0M0 and T2N0M0 lesions, are readily controlled by radiotherapy. Studies have shown that control varies with the dose of radiotherapy delivered to the tumour. Other factors, including the dose per fraction and the time over which the treatment schedule is delivered are also important. The varying biological effectiveness of a number of different dose fraction time schedules used in the management of laryngeal tumours of different stages are considered, the end points being tumour control and associated morbidity. Special attention has been given to the length of time over which the schedule is delivered. Of the schedules examined the results would suggest that a dose of 60 Gy given in 25 fractions over a period of 35 days is the best of the six schedules studied for T1, T2, T3 and T4 lesions with minimal associated morbidity. It is possible, however, that the poor results shown on the Kaplan Meier curves for patients treated with the schedule of 60 Gy in 30 fractions over a period of 42 days could be due to geographical misses of the tumours as 56% were treated without a beam directed shell. The poor result obtained when patients were treated with the schedule of 60 Gy given in 30 fractions over 49+ days may be due to tumour repopulation occurring during the rest period though the possibility of geographical misses may contribute to the poor tumour control results. Mathematical modelling using linear quadratic analysis suggests that the shorter the period of time over which the treatment is given the better chance of achieving tumour control irrespective of the stage of the disease. These models were developed for patients treated with a beam directed shell thus excluding those patients who are most likely to be at risk from a geographic miss of the tumour. Linear quadratic analysis of the treatment data suggests that the ratio alpha/beta for tumour cells is estimated in the region of 13 Gy. For T1 lesions the tumour doubling time is in the order of 6 days, with longer doubling times for the more advanced stages. The analysis provides some support for investigative use of accelerated treatment schedules. This analysis also shows the importance of using beam directed shells when treating small fields especially in the head and neck region. PMID- 8435201 TI - Control of nausea and vomiting with ondansetron in patients treated with intensive non-cisplatin chemotherapy for acute myeloid leukaemia. AB - 18 consecutive patients with acute myeloid leukaemia (AML) treated with 34 cycles of intensive chemotherapy received ondansetron as antiemetic treatment. 14 patients were chemotherapy-naive, while 4 patients were treated for relapsed leukaemia. All patients received at least one cycle of chemotherapy, 11 patients (61%) received two cycles and 5 patients (28%) received three cycles. The remission induction regimen consisted of cytarabine 200 mg/m2 daily from day 1 to day 7, in combination with an anthracycline or amsacrine on 3 days. During the second and third cycle the dose of cytarabine was increased. Ondansetron was administered as follows: 8 mg intravenously before the start of chemotherapy, followed by 8 mg orally three times daily for 10 days. 50% of patients had no episodes of vomiting during the first cycle of chemotherapy and 78% had less than five episodes of vomiting over 10 days. 72% of patients had no or only mild nausea. These high response rates were maintained during the subsequent cycles. No side-effects due to ondansetron were registered. These data indicate that ondansetron is efficacious in preventing nausea and vomiting in patients with AML treated with intensive chemotherapy. PMID- 8435202 TI - Phase II study of daily oral miltefosine (hexadecylphosphocholine) in advanced colorectal cancer. AB - 34 patients with metastatic colorectal cancer were treated with the ether lipid miltefosine (hexadecylphosphocholine). Most patients received 3 x 50 mg daily, while in 11 patients the dose could be escalated to 4 x 50 mg daily. Nausea and vomiting were the most frequent side-effects occurring in all but 3 patients, nephrotoxicity was observed in 11 patients. Leucocytosis was observed in 24 and thrombocytosis in 17 patients. 28 patients are evaluable for response. 1 patient obtained a partial response of liver metastases for a duration of 8 months. 3 patients had stable disease while 24 progressed during treatment. We conclude that miltefosine in this dose and schedule has limited activity in colorectal cancer. PMID- 8435203 TI - HLA antigen frequencies in renal transplant recipients and non-immunosuppressed patients with non-melanoma skin cancer. AB - An increased frequency of human leukocyte antigen (HLA)-DR1 was found in 49 non immunosuppressed patients with non-melanoma skin cancer (NMSC), being highest in patients under the age of 60 with multiple squamous cell carcinomas (SCC). Of 266 patients receiving long-term immunosuppression following renal transplantation 46 (17%) were found to have NMSC. No increase in HLA-DR1 was found in renal transplant recipients (RTR) with non-melanoma skin cancer (RTR+C) when compared with matched renal transplant recipients without skin cancer (matched RTR-C), or when compared with healthy controls. There was an increased frequency of DQw2 in RTR+C, most pronounced in RTR with SCC (61.9% compared with 18.75% in matched RTR C), giving a relative risk of 13.98. We found statistically significant differences in the frequency of a number of HLA antigens on comparing RTR+C with healthy controls, but none of these differences were found when we compared RTR+C against matched RTR-C. PMID- 8435204 TI - Psychiatric disorder in patients with advanced breast cancer: prevalence and associated factors. AB - The prevalence of psychiatric disorder and associated factors has been examined in 139 women with advanced breast cancer. Patients completed a self-report assessment of mood, the Hospital Anxiety and Depression Scale (HAD). They were also interviewed to obtain sociodemographic details, UICC performance status and past psychiatric history. Overall, 35 (25%) scored 11 or above (out of a maximum of 21) on either the anxiety or the depression subscales, or both, of the HAD and were therefore probable cases of anxiety and/or depression. These patients are likely to benefit from psychosocial intervention. Clinical anxiety was unrelated to any sociodemographic or disease related factors. Clinical depression was significantly more prevalent amongst patients in the lower socioeconomic classes (P = 0.01) and those with poor performance status (P = 0.007). Depression can be difficult to detect in patients with advanced breast cancer and these factors may be useful indicators to clinicians of patients at high risk of this disorder. PMID- 8435205 TI - Decreased efficacy of cyclophosphamide, epirubicin and 5-fluorouracil in metastatic breast cancer when reducing treatment duration from 18 to 6 months. AB - The impact of treatment duration on survival and progression-free survival is uncertain in metastatic breast cancer. In this trial 359 patients were randomised to receive cyclophosphamide, epirubicin and 5-fluorouracil (CEF) once every 3 weeks for a maximum of 18 months or identical chemotherapy for a maximum of 6 months. Following progressive disease (PD) or severe toxicity CEF was discontinued before the scheduled maximum duration. A second series of CEF continued for a maximum of 12 months was offered to patients with PD more than 3 weeks after completing a maximum of 6 months of CEF. Both groups received tamoxifen (30 mg daily) until PD, and premenopausal patients also received ovarian irradiation. After 6 months 254 evaluable patients were unprogressive. Survival and progression-free survival were significantly longer in 127 patients continuing CEF than in 127 patients interrupting CEF at 6 months (chi 2 = 17.6, P = 0.00003 and chi 2 = 4.7, P = 0.03, respectively). The results of the second series of CEF were discouraging with only one complete response in 44 evaluable patients. In conclusion, prolonged chemotherapy for 18 months is superior to identical chemotherapy for 6 months in the treatment of metastatic breast cancer. PMID- 8435206 TI - Polyunsaturated fatty acids in serum phospholipids and risk of breast cancer: a case-control study from the Janus serum bank in Norway. AB - We have tested the hypothesis that specific polyunsaturated fatty acids (PUFA) of the n-3 and n-6 families, as measured in serum phospholipids, are negatively associated with the risk of breast cancer. The study is based on serum samples from women who have donated blood to the Janus serum bank at the University Hospital in Oslo, Norway. It consists of sera from 87 women who developed breast cancer (cases) subsequent to blood donation and 235 women who were free of any diagnosed cancer (controls), but were of similar age and had similar blood storage time as the cases. We measured fatty acids (monounsaturated, polyunsaturated and saturated) in serum phospholipids, and made comparisons between cases and controls. The results showed that there was an inverse relation between the n-6 PUFA linoleic acid (18:2n-6) and risk of breast cancer, but this association was restricted to women who were 55 years and younger. In this age group, the relative risk (odds ratio) of women in the highest quartile of linoleic acid was 0.4 (95% confidence limits, 0.2 and 1.0) compared with women in the lowest quartile, and there was a negative trend over quartiles of linoleic acid (Mantel's chi for trend = -2.49, P < 0.02). No association was noted between the n-3 PUFA of marine oil origin and breast cancer risk. If the measured concentration of linoleic acid in serum phospholipids reliably reflects dietary intake, these data suggest that linoleic acid in the diet may decrease breast cancer risk among women at premenopausal and perimenopausal age. No similar association with n-3 unsaturated fatty acids was observed. It is noteworthy that none of the measured fatty acids (saturated or unsaturated) showed a positive association with breast cancer risk. PMID- 8435207 TI - Urban-rural variation in cancer incidence in Denmark 1943-1987. AB - Urban and rural cancer incidence in Denmark in 1943-1987 was analysed. A consistent urban excess was found for all sites combined for individuals of each sex, irrespective of age at diagnosis. The capital:rural incidence ratio was 1.42 for men and 1.25 for women, and these ratios were not affected to any great extent using another definition of urban areas. Urban:rural ratios were highest for cancers of the respiratory, urinary and upper digestive tracts. The differences cannot be explained by tobacco and alcohol consumption alone. Other risk factors linked to urbanisation may contribute importantly to the "urban factor", and analytical studies of data at an individual level are required to establish their relative importance. Our findings contradict the generally accepted view that there is no urban-rural difference in cancer incidence in the relatively small, homogeneous population of Denmark. PMID- 8435208 TI - Differential expression of thymidine kinase gene in two subpopulations of a rat tumour correlates with their tumorigenic and cell division potential. AB - We have studied the expression of the thymidine kinase (TK) gene in two kinetically heterogenous populations of a rat tumour cell line--the Zajdela ascitic hepatoma (ZAH). We have demonstrated that the TK gene is differentially expressed in the two cell types. The more tumorigenic and rapidly dividing subpopulation shows higher levels of mRNA and enzyme activity for TK. In addition, we have shown that the tumorigenic cells accumulate the primary unspliced transcript and utilise only part of it for maturation. It is, therefore, likely that ZAH cells regulate their division and possibly tumorigenic potential by regulating the expression of the TK gene. PMID- 8435209 TI - Effect of whole body hyperthermia on cis-diamminedichloroplatinum (II)-induced antitumour activity and tissue Pt-distribution: do anaesthetics influence the therapeutic ratio? AB - Thermal enhancement of cis-diamminedichloroplatinum (II) (DDP)-mediated antitumour activity and normal tissue toxicities by whole body hyperthermia were compared in a F344 rat model under different anaesthetic conditions. Whole body hyperthermia (WBH: 120 min at 41.5 degrees C) enhanced both DDP-mediated antitumour activity and toxic side-effects. Our present study shows that anaesthetics might influence the thermal enhancement ratios (TER) calculated for DDP-mediated normal tissue toxicity but did not influence the TER calculated for antitumour activity. The TER calculated for DDP-mediated antitumour activity was 2.9. As a result of the anaesthetics used, the TER calculated for kidney and gastrointestinal toxicity ranged from 1.8 to 4.5 and from 1.2 to 2.3, respectively. The TER estimated for DDP-mediated general toxicities varied between 2.9 and 4.0 for weight loss, and from 2.0 to 2.3 based on the LD50. The differential effect of anaesthetics on TER calculated for antitumour activity and normal tissue toxicity led to different therapeutic ratios. For example the therapeutic ratio for combined WBH and DDP, using kidney damage as an end-point for normal tissue damage, ranged from 0.6 (without anaesthesia) to 1.6 (using nembutal as anaesthetic). The significantly elevated platinum levels in serum, kidney, jejunum and tumour tissue after WBH treatment may explain the thermal enhancement of DDP-mediated antitumour activity and side-effects but no correlation could be found for the differences in DDP-mediated normal tissue toxicities induced by the anaesthetics. PMID- 8435210 TI - Effect of D,L-verapamil, verapamil enantiomers and verapamil metabolites on the binding of vincristine to alpha 1-acid glycoprotein. AB - Vincristine binding to solutions of alpha 1-acid glycoprotein (AGP, 2 mg/ml) and the effect of D,L-verapamil, verapamil enantiomers and the verapamil metabolites norverapamil and D617 were investigated in vitro using equilibrium dialysis and 3H-labelled vincristine. Vincristine binding to AGP (52.3 +/- 3.6%) was concentration independent over the range 0.002-2.0 micrograms/ml. The displacement of vincristine from AGP varied between 25.1 and 81.3% with D,L verapamil and verapamil enantiomers added at concentrations in the range 5-50 micrograms/ml. In contrast, the displacement by D617 (5-100 micrograms/ml) was weaker and varied between 0 and 47%. The displacement at 20 micrograms/ml produced by D,L-verapamil, R-verapamil, S-verapamil and norverapamil was 53.1%, 56.8%, 58.9% and 53.9%, respectively, was more than double that for D617 (25%; P = 0.002). It is concluded that vincristine, D,L-verapamil and verapamil isomers and metabolites interact at binding sites on AGP. These interactions may be clinically important in multidrug resistance, for example in cancer patients with elevated levels of AGP undergoing treatment with verapamil and vinca alkaloids. PMID- 8435211 TI - Effect of endocrine therapy on growth of T61 human breast cancer xenografts is directly correlated to a specific down-regulation of insulin-like growth factor II (IGF-II). AB - Insulin-like growth factors I and II (IGF-I and IGF-II) are potent mitogens for some human breast cancer cell lines, and expression of IGF-II mRNA in the oestrogen receptor-positive (ER+) and oestradiol (E2) stimulated human breast cancer cell line T47D is increased by E2, suggesting a role for IGF-II in the mitogenic response to E2. Very little information is available from the literature on the relation between growth inhibition by endocrine therapy and cellular production of IGF-II. Here we report on the effect of E2 and tamoxifen (TAM) on IGF-II mRNA and protein expression in the ER+T61 human breast cancer xenograft. Growth of the T61 tumour is inhibited by treatment with E2 and TAM. Ribonuclease (RNAse) protection assays with human- and mouse-specific IGF-II antisense probes were used to study the regulation of IGF-II mRNA by E2 and TAM in the tumour. IGF-II protein expression was studied by radioimmunoassay. Untreated T61 tumours have a high baseline expression of IGF-II mRNA. TAM treatment of T61 tumours, which results in inhibition of tumour growth without tumour regression, reduced IGF-II mRNA expression approximately 10-fold after 48 h of treatment. E2 treatment of T61 tumours, which results in tumour regression, was accompanied by a more pronounced decrease in IGF-II mRNA expression in the tumour cells; 96 h after initiation of E2 treatment, there was almost no detectable IGF-II mRNA. Analyses of IGF-II protein showed that both treatments significantly reduced the concentration of IGF-II protein in the tumours. This down-regulation was found to be specific for IGF-II, since analyses of the effect of E2 on the expression of IGF-I mRNA, 36B4 mRNA, transforming growth factor alpha(TGF-alpha) mRNA, and epidermal growth factor (EGF) receptor mRNA in T61 tumours did not reveal any down-regulation. To further study the relation between inhibition of tumour growth and down-regulation of IGF-II, we exposed T61 tumours to a monoclonal antibody, alpha-IR3, which abolishes the physiological effect of IGF-I and IGF-II by blocking the binding of both growth factors to the type I IGF receptor. Treatment with alpha-IR3 resulted in inhibition of tumour growth during treatment.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8435212 TI - Response to third-line endocrine treatment for advanced breast cancer. AB - In a retrospective analysis we have identified 55 patients who have received three endocrine treatments for advanced breast cancer. 42% of these patients have benefitted from third-line endocrine treatment in terms of disease stabilisation, symptom relief or objective response and this was translated into statistically significant (P < 0.01) improved median survival of these patients (34 months) compared with those with progressive disease on third-line treatment (14 months). This suggests that third-line endocrine treatment might be of benefit to a number of patients with advanced breast cancer. PMID- 8435213 TI - Staging and surgery for colorectal cancer. AB - Staging of colorectal cancer has become increasingly important to select groups of patients for limited or more extensive surgery, and for adjuvant radiotherapy and chemotherapy. The main treatment is still surgery, but subgroups may benefit from adjuvant therapy, even accepting additional side effects. Accurate staging is necessary to define different treatment groups. A critical review is given of the present methods of clinicopathological staging. PMID- 8435214 TI - Systemic treatment of colorectal cancer. PMID- 8435215 TI - Organisation of screening. AB - The 'Europe against Cancer' programme aims to introduce systematic screening for breast cancer for women aged 50-69 and for cervical cancer for women aged 25-69. The programme initiated pilot projects on breast cancer screening in several European countries in 1989-1990. This initiative was followed by training for radiologists. European guidelines for quality assurance in breast cancer screening became available in 1992, and a working party on treatment of small breast lesions was formed. The 'Europe against Cancer' programme also launched pilot projects in cervical cancer screening and a cervical cancer screening surveillance programme in 1992. PMID- 8435216 TI - Adjuvant systemic therapy in breast cancer. AB - Systemic adjuvant therapy has improved the prognosis of patients with primary breast cancer. Meta-analyses have demonstrated that approximately one fourth of deaths can be avoided among younger women treated with multiple cytotoxic drug regimens and among older women treated with tamoxifen. However, with the treatments available today many aspects related to the optimal therapy, taking into account the physical, psychological and socioeconomic consequences, are still open. This review discusses some of the major open questions related to the effectiveness of the adjuvant systemic therapy in terms of its ability to reduce recurrence rate and mortality. PMID- 8435217 TI - Regional therapy of melanoma. AB - Little progress has been made in the systemic treatment of melanoma, that is for disseminated stage IV disease. However, the tumour resistance to therapy, especially chemotherapy can be overcome in melanoma by high doses of anticancer agents administered regionally. The purpose of this paper is to illustrate this concept by two modes of regional treatment namely: (1) isolation perfusion of the limbs with high doses of cytokines and chemotherapy under hyperthermia and (2) local treatment of metastatic melanoma. The third part will be devoted to the role of another regional treatment, radiotherapy, where the association with hyperthermy also looks promising. PMID- 8435218 TI - Advances in systemic treatment of malignant melanoma. AB - This paper reviews recent developments in the systemic treatment of advanced malignant melanoma. In the introduction emphasis is given to prevention and early detection of this disease. Metastatic malignant melanoma patients have a median survival of less than 1 year in the most favourable situation. Adjuvant chemotherapeutic treatment after initial surgery has not had an impact on prognosis, while immunological manipulations with interferon alfa or other agents may prove beneficial after primary surgery. In advanced disease which cannot be palliated by surgery, many approaches are under investigation. Modulation of the patient's immune response can be achieved with vaccines, monoclonal antibodies, interleukin-2 and interferons, as single agents or in combination between themselves or with peripheral blood mononuclear cells or with tumour infiltrating lymphocytes or even with chemotherapy. Immunological approaches yield a 20-30% response rate, with some possibly long-term responses. Chemotherapeutic agents have a 10-30% response rate, which is usually of short duration. Combinations of chemotherapeutic agents can increase the response rate to 50%, but an impact on ultimate survival seems unlikely. Randomised studies have shown that modulation of chemotherapy with interferon or tamoxifen improves response rates. Clinicians should be encouraged to enter their patients with malignant melanoma in therapeutic trials. PMID- 8435219 TI - Surgery in soft tissue sarcomas. AB - The surgical treatment of soft tissue sarcomas improved in the last decade, with better regional control and an increased number of limb sparing operations, but procedures and criteria of indication are not unified. Moreover, a great discrepancy exists in the incidence rate of local recurrence reported in literature, and also major centres denounce a high rate of local failures. The major predictive parameters of adequate regional control are the size and location of primary lesion, the pathological grading, previous treatments and the quality of surgical margins. Results in terms of regional control of 417 cases treated at our institute in the period 1974-1984 are analysed and discussed. Local failure occurred in 113 cases (27% crude, 31% actuarial risk at 5 years) and has been analysed according to factors which had impact on local failures: pathological grading (low grade 24% local recurrence vs. high grade 35% recurrence, P = 0.05), site (extremity and girdle 26% vs. trunk and head and neck 47%, P = 0.001), previous surgical treatment (32% for lesions recurrent at entry vs. 43% for virgin tumours, P = 0.05), quality of margins (adequate surgery 24% vs. marginal surgery 47%, P < 0.001); intralesional operations are excluded from this series. Histopathology is stratified in four categories that can actually influence the treatment schedule: low grade, spindle cell type high grade, small blue cell, miscellaneous sarcomas of different or unclear histogenesis. The size is detailed in different definitions of small or large, in a site-size relationship which may be useful in surgical practice, with no prognostic purposes. Finally, the adequacy of a surgical treatment is evaluated and discussed by the quality of surgical margins, defined according to the concept of compartment. A surgical indication rationale is, therefore, proposed taking into account the above-mentioned parameters and conclusive points of discussion. PMID- 8435220 TI - Aspects of surgery in ovarian and endometrial carcinoma. AB - In ovarian cancer and endometrial cancer the surgeon plays an important role in both the staging procedure and in the removal of as much of the tumour as possible. Although uniform treatment policies have not been developed, a better understanding of the pattern of spread in both tumours allows for accurate staging and can be of help in selecting patients for more extended treatment and saving others from unnecessary overtreatment. PMID- 8435221 TI - Systemic treatment in disseminated endometrial cancer. AB - Both hormonal agents and chemotherapy are of value in the treatment of selected patients with endometrial cancer. In unselected patients with advanced disease about 25% respond to progestational agents and 40% to combination chemotherapy. The choice between the two treatments is made on the basis of a number of prognostic factors, such as receptor status, tumour grade, performance status and tumour burden. Further improvement of treatment outcome is to be expected from new agents such as gonadotrophin releasing hormone analogues, taxol and modulation of 5-fluorouracil. PMID- 8435222 TI - Chemotherapy for ovarian cancer. PMID- 8435223 TI - Oncogenes and tumour suppressor genes in transgenic mouse models of neoplasia. PMID- 8435224 TI - HER-2/neu amplification in human breast cancer: Southern or slot blotting for amplification analysis? PMID- 8435225 TI - Ondansetron in the prophylaxis of nausea and vomiting induced by carboplatin combination chemotherapy. PMID- 8435226 TI - Recurrent ovarian carcinoma: salvage treatment with platinum in patients responding to first-line platinum-based regimens. PMID- 8435227 TI - P53 immunostaining in melanocytic lesions. PMID- 8435228 TI - Unexpected Prad-1 amplification in multiple simultaneous localisations of squamous cell carcinoma of the head and neck. PMID- 8435229 TI - Care versus cure: a nursing perspective. PMID- 8435230 TI - Defining nursing administration terms (continued). PMID- 8435231 TI - Transformations of hydroxy cyclic sulfates: stereospecific conversion into 2,3,5 trisubstituted tetrahydrofurans. AB - 1,2-Cyclic sulfates have been prepared from O-protected ricinoleate and ricinelaidate esters. Upon deprotection of the 12-hydroxy moiety, the resulting 12-hydroxy-9,10-cyclic sulfates underwent stereospecific cyclization to the corresponding 2,3,5-trisubstituted tetrahydrofurans. The cyclization occurs by backside attack of the hydroxy oxygen on the distal carbon of the 1,2-cyclic sulfate, with inversion at that center. PMID- 8435232 TI - Elective replacement of the aortic root in Marfan's syndrome. AB - We offer elective aortic replacement ot those we regard as being at high risk. The aortic root dimension and its rate of increase are the best predictors we have. We regard 5.5 cm as the probable upper limit and we are inclined to advocate surgery at an earlier stage in high risk families and in women planning pregnancy. These operations are planned for a calculated gain in life expectancy and it would be reasonable for there to be a degree of centralisation of referral and development of surgical expertise. We use beta-blockade for life, both before and after surgery, in all patients with Marfan's syndrome with aortic root enlargement. The data on which these recommendations are based are incomplete and we can only hope that with an increasing number of carefully documented cases we will refine them and improve upon them in the future. The concept of a "forme fruste" or a "Marfanoid aorta" in the absence of the syndrome is highly questionable so the comments made apply only to patients with Marfan's syndrome- not to other forms of annuloaortic ectasia or other less well characterised forms of aortic root disease. PMID- 8435233 TI - Cardiovascular manifestations of Marfan's syndrome: improved evaluation by transoesophageal echocardiography. AB - OBJECTIVES: To assess the value of transoesophageal echocardiography in patients with Marfan syndrome particularly those with suspected aortic pathology or where conventional transthoracic imaging was suboptimal. DESIGN AND PATIENTS: Eleven patients with Marfan syndrome. Seven patients were studied because of suspected aortic dissection and four because of inadequate transthoracic imaging. INTERVENTION: Transoesophageal echocardiography and colour Doppler flow mapping by a 5 MHz single plane transoesophageal probe. RESULTS: Aortic dissection was identified in six patients with subsequent diagnostic confirmation in all six. No dissection was found in one patient in whom the diagnosis had been suspected clinically. Estimates of aortic root dimensions and assessment of aortic and mitral valve pathology were made in four other patients with inadequate transthoracic imaging. CONCLUSIONS: Transoesophageal echocardiography provides rapid diagnostic information in patients with Marfan syndrome with suspected aortic dissection and enhances the assessment of cardiovascular manifestations of this condition. PMID- 8435234 TI - Doppler echocardiographic evaluation of valve regurgitation in healthy volunteers. AB - OBJECTIVE: To study the prevalence and the characteristics of physiological valve regurgitation. DESIGN: Pulsed wave Doppler echocardiography, continuous wave Doppler echocardiography and Doppler colour flow mapping were performed prospectively in healthy volunteers. SETTING: Echocardiography laboratory in a city hospital. PATIENTS: 32 consecutive healthy volunteers (age 21-49 years, mean age 29.4). MAIN OUTCOME MEASURES: Identification of regurgitation with colour Doppler flow mapping and measurement of the jet area, jet length, and maximal velocity of the regurgitation. RESULTS: Regurgitation was recorded at the pulmonary (100%), tricuspid (100%), mitral (56%), and aortic valves (6%). The velocity of pulmonary and tricuspid regurgitation was similar to that predicted from the pressure gradient calculated from the Bernoulli equation. The jet area and jet length were generally small. CONCLUSION: Trivial regurgitation from the pulmonary, tricuspid, and mitral valves is common in healthy people. It is important to take such regurgitation into account when valve disease is diagnosed. PMID- 8435235 TI - Free radical activity and left ventricular function after thrombolysis for acute infarction. AB - BACKGROUND: Experimental data suggest that reperfusion injury involving free radicals contributes to the impairment of left ventricular function after successful thrombolysis. METHODS: In 72 patients presenting with acute myocardial infarction, markers of free radical activity were measured before streptokinase and two hours later. Thiobarbituric acid reactive material (TBA-RM) reflects lipid peroxidation by free radicals, and the concentration of plasma total thiols (34 patients) reflects oxidative stress. Coronary arteriography was performed at 18-72 hours after thrombolysis to determine coronary patency, and left ventricular function was assessed by ventriculography and from QRS scoring of the electrocardiogram. RESULTS: The infarct related artery was patent (Thrombolysis In Myocardial Infarction Trial grade 2 or better) in 60 (83%) and occluded in 12. In the 60 with a patent artery, the concentration of TBA-RM increased after streptokinase by (mean (SD)) 9.2 (14.0) nmol/g albumin, whereas in the 12 with an occluded artery TBA-RM decreased by 7.0 (11.3) nmol/g albumin (p < 0.01 between groups). In those with a patent artery the rise in TBA-RM associated with thrombolysis correlated with left ventricular ejection fraction (R = -0.41, p < 0.002), and with the QRS score (R = +0.38, p = 0.003). Plasma total thiol concentrations decreased by 12.7 (31.1) mumol/l in those with a patent artery, and this decrease associated with thrombolysis correlated with left ventricular ejection fraction (R = +0.39, p < 0.02) but not with the QRS score (R = -0.2, NS). CONCLUSIONS: These findings suggest that reperfusion injury mediated by free radicals may be of clinical importance in humans. PMID- 8435236 TI - Circadian variation of tissue plasminogen activator and its inhibitor, von Willebrand factor antigen, and prostacyclin stimulating factor in men with ischaemic heart disease. AB - OBJECTIVES: To determine whether plasma concentrations of tissue plasminogen activator antigen, von Willebrand factor antigen, and prostacyclin stimulating factor and plasminogen activator inhibitor activity show circadian variation in men with ischaemic heart disease. DESIGN: Blood samples were obtained every four hours for 24 hours from 10 men with ischaemic heart disease. The men were ambulant from 08:10 until 00:00 when they went to bed and they remained in bed until 08:00 the following morning. PATIENTS: Ten men with positive diagnostic exercise tolerance tests with no significant past history, who were not regularly taking any medical treatment except for glyceryl trinitrate. RESULTS: There was significant circadian variation in plasminogen activator inhibitor activity (p = 0.001) (peak value 04:00 and trough value 20:00), but not in plasma concentrations of tissue plasminogen activator antigen, von Willebrand factor, or prostacyclin stimulating factor. CONCLUSION: Men with ischaemic heart disease showed a significant circadian variation in fibrinolysis. The combination of peak values of plasminogen activator inhibitor activity and failure of plasma concentrations of tissue plasminogen activator antigen to increase in the early morning must predispose to thrombosis at this time. The circadian variation in fibrinolysis may contribute to the increased incidence of myocardial infarction in the morning. PMID- 8435237 TI - Reduction in left ventricular wall thickness after deconditioning in highly trained Olympic athletes. AB - BACKGROUND: Clinical distinction between athlete's heart and hypertrophic cardiomyopathy in a trained athlete is often difficult. In an effort to identify variables that may aid in this differential diagnosis, the effects of deconditioning on left ventricular wall thickness were assessed in six highly trained elite athletes who had competed in rowing or canoeing at the 1988 Seoul Olympic Games. Each of these athletes showed substantial ventricular septal thickening associated with training (13-15 mm) which resembled that of hypertrophic cardiomyopathy. METHODS: The athletes voluntarily reduced their training substantially for 6-34 weeks (mean 13) after the Olympic competition. Echocardiography was performed at peak training and also after deconditioning, and cardiac dimensions were assessed blindly. RESULTS: Maximum ventricular septal thickness was 13.8 (0.9) mm in the trained state and 10.5 (0.5) in the deconditioned state (p < 0.005) (change 15-33%). CONCLUSIONS: The finding that deconditioning may be associated with a considerable reduction in ventricular septal thickness in elite athletes over short periods strongly suggests that these athletes had a physiological form of left ventricular hypertrophy induced by training. Such a reduction in wall thickness with deconditioning may help to distinguish between the physiological hypertrophy of athlete's heart and primary pathological hypertrophy (for example, hypertrophic cardiomyopathy) in selected athletes with increased left ventricular wall thickness. PMID- 8435238 TI - Familial aggregation of idiopathic dilated cardiomyopathy: clinical features and pedigree analysis in 14 families. AB - OBJECTIVE: A recent prospective study in patients with dilated cardiomyopathy has reported that the disease is familial in at least 20% of cases, but the pattern of inheritance could not be ascertained. The presence of an autosomal dominant pattern, such as seen in hypertrophic cardiomyopathy, could make it possible to search for single gene defects with linkage analysis, whereas polygenic inheritance would be consistent with the autoimmune hypothesis. To assess the pattern of inheritance, we retrospectively identified patients with familial disease and assessed their first degree relatives (parents, siblings and children) for dilated cardiomyopathy. DESIGN AND PATIENTS: The family history of 105 consecutive patients with dilated cardiomyopathy was reviewed and 14 who had at least one first degree relative with documented disease were identified as probands. Their healthy relatives (109) were studied by physical examination, electrocardiography, M mode and cross sectional echocardiography, and were classified as unequivocally normal or as potential carriers. The potential carriers had abnormal electrocardiography with either at least one echocardiographic measurement of left ventricular cavity dimension or percentage fractional shortening outside 2 SDs of normal values (based on age and body surface area). The potential carriers underwent 24 hour Holter monitoring and maximal treadmill exercise. RESULTS AND CONCLUSION: Twenty three relatives (21%) were classified as potential carriers: 12 had an increased left ventricular end diastolic dimension, with reduced percentage fractional shortening in three; 11 had an abnormal electrocardiogram and increased end diastolic dimension, with reduced percentage fractional shortening in five. Such abnormalities were very mild and follow up is necessary to find whether such changes represent early disease. Pedigree analysis was most consistent with polygenic inheritance. PMID- 8435239 TI - Identification of a mutation in the beta cardiac myosin heavy chain gene in a family with hypertrophic cardiomyopathy. AB - OBJECTIVE: To investigate the molecular genetic basis of the cause of disease in a family with hypertrophic cardiomyopathy. BACKGROUND: Mutation within the beta cardiac myosin heavy chain gene has been shown to be the pathogenetic mechanism underlying the disease in several families, though clear evidence of heterogeneity has been reported. PATIENTS: A family with a history of hypertrophic cardiomyopathy. RESULTS AND CONCLUSION: This paper reports a mutation at aminoacid position 908 within exon 23 of the beta cardiac myosin heavy chain gene, resulting in a conversion of a leucine to valine. This base substitution was identified in an individual with a confirmed family history but with equivocal symptoms of the disease. Inheritance of the mutation by his symptom free juvenile offspring demonstrates the application of the technique to presymptomatic diagnosis. PMID- 8435240 TI - Dysplastic conditions of the right ventricular myocardium: Uhl's anomaly vs arrhythmogenic right ventricular dysplasia. AB - OBJECTIVE: Since 1905 there have been many reports of cases in which the right ventricle was deficient in myocardium. Several terms have been used to describe this condition. Of these, "Uhl's anomaly" and "arrhythmogenic right ventricular dysplasia" are most often used. Our study investigates the relation between these entities. METHOD: Five cases with a primary deficiency of the right ventricular musculature were examined. The findings were compared with those published reports to evaluate the similarities and differences between Uhl's anomaly and arrhythmogenic dysplasia. RESULTS: The five cases showed two patterns of myocardial deficiency in the right ventricle. On the one hand, the parietal wall was paper thin with complete absence of musculature and apposition of the endocardial and epicardial layers. On the other hand, patchy, localised fibrofatty tissue replacement was found within the parietal musculature. Evidence from our cases, combined with analysis of other publications, showed different modes and timing of clinical presentation of the patients with these two anatomical conditions, congestive heart failure or arrhythmia. CONCLUSIONS: The conditions variously described as Uhl's anomaly and arrhythmogenic dysplasia are separate and distinct morphological entities. PMID- 8435241 TI - Right ventricular dysplasia: a clinical and pathological study of two families with left ventricular involvement. AB - BACKGROUND: Right ventricular dysplasia is a heart muscle disease of unknown cause that is often familial and is anatomically characterised by adipose or fibroadipose infiltration of the right ventricular myocardium. It is generally regarded as a selective disorder of the right ventricle. AIM: To investigate the prevalence and characteristics of left ventricular involvement in two families in which at least one member had right ventricular dysplasia confirmed at necropsy. METHODS AND RESULTS: Eight patients were found to be affected by right ventricular dysplasia. In three of them this was confirmed at necropsy. Echocardiography or angiography or both showed left ventricular involvement in seven. This ranged from localised wall motion abnormalities to moderate or severe left ventricular dysfunction. The disease was progressive in four cases. At necropsy the left ventricular myocardium showed predominant fibrosis and degenerative changes of the myocardial cells. There were areas of myocardial thinning with fatty infiltration at the apex in two patients. CONCLUSIONS: Familial right ventricular dysplasia can be a progressive disorder that affects the left ventricle. Advanced disease may be clinically confused with dilated cardiomyopathy. PMID- 8435242 TI - Arrhythmogenic right ventricular dysplasia: an uncommon cause of ventricular tachycardia in young and old? AB - Right ventricular dysplasia is a little understood condition and is almost certainly underdiagnosed as an important cause of recurrent ventricular tachycardia and sudden death. This report describes two patients with right ventricular dysplasia. Their clinical presentation reflects the remarkable diversity of the disease while the potentially life-threatening nature of their arrhythmias and their lack of response to medical treatment justified the antiarrhythmic surgical procedure of right ventricular disarticulation. PMID- 8435243 TI - Differing effects of right ventricular pacing and left bundle branch block on left ventricular function. AB - OBJECTIVE: To compare the different effects of right ventricular pacing and classic left bundle branch block on left ventricular function. DESIGN: Retrospective and prospective study of 48 patients by electrocardiography, and M mode, cross sectional, and Doppler echocardiography. SETTING: A tertiary cardiac referral centre. PATIENTS: 48 patients (age range 21 to 89 years, 15 women), 24 with a VVI pacemaker implanted and 24 with classic left bundle branch block. Functional mitral regurgitation was present in all those with right ventricular pacing and 22 of those with left bundle branch block. RESULTS: Age, RR interval, and left ventricular size were similar in the two groups, as were conventional measurements of overall systolic function: shortening fraction and pre-ejection and aortic ejection times. In right ventricular pacing, however, QRS duration (p < 0.01) and electromechanical delay were much longer (p < 0.001), whereas the time intervals from onset of mitral regurgitation to aortic opening (contraction time) and from A 2 to the end of mitral regurgitation (relaxation time) were consistently shorter (p < 0.01) than corresponding values in patients with left bundle branch block. Reversed splitting of the second heart sound was much commoner in left bundle branch block (p < 0.02), and only these patients showed an early systolic ventricular septal contraction. Its onset followed the initial deflection of the QRS complex by 40(15) ms and preceded mitral regurgitation by a small but consistent interval of 10 ms (p < 0.01). The onset of posterior wall thickening was synchronous with the onset of mitral regurgitation in right ventricular pacing but much later (p < 0.01) in patients with left bundle branch block. The extent of incoordinate wall motion measure as relative dimension change during pre-ejection and isovolumic relaxation period was much greater (p < 0.01) in left bundle branch block. These major differences were not altered by left ventricular cavity size in either group, nor by the presence of previous left bundle branch block in patients who were subsequently paced. CONCLUSIONS: The left ventricle seems to be activated much more rapidly with right ventricular pacing than with left bundle branch block. This applies even when left bundle branch block is present before pacing. Electromechanical delay, contraction and relaxation times, and extent of incoordinate ventricular wall motion differ strikingly between the two conditions. The use of right ventricular pacing as an experimental model of left bundle branch block in humans must be re-examined. PMID- 8435244 TI - Atrial adaptive rate pacing in sick sinus syndrome: effects on exercise capacity and arrhythmias. AB - OBJECTIVE: To test the hypotheses that adaptive rate atrial (AAIR) pacing: significantly increases maximal exercise capacity, and results in significant suppression of supraventricular and ventricular arrhythmia compared with fixed rate atrial (AAI) pacing. DESIGN: Prospective, randomised, single blind, crossover study with maximal treadmill exercise testing and 24 hour ambulatory electrocardiographic monitoring in AAIR and AAI modes. SETTING: Regional pacing centre. PATIENTS: 30 consecutive patients (mean SD age 65 (12) years) with sick sinus syndrome who required permanent pacing, without evidence of conduction disturbance on 12 lead electrocardiograms or 24 hour ambulatory electrocardiographic monitoring and without other cardiovascular or systemic disease. INTERVENTIONS: Activity sensing or minute ventilation driven systems (AAI/AAIR) were implanted alternately. RESULTS: The mean (SD) peak heart rate in AAI mode was 122(28)v 130(22) in AAIR mode (p < 0.02) for the whole group and 104(17) v 120(5) (p < 0.003) for the patients with chronotropic incompetence. Exercise time was 12.3 (4.1) minutes in AAI and 12.3 (3.8) minutes in AAIR mode (NS) in the chronotropically incompetent patients. There were no significant differences in the Borg scores at peak exercise in AAI v AAIR mode in either group. The frequency per hour of atrial and ventricular arrhythmias showed no significant differences between the two modes in either the group as a whole or in the subgroups with chronotropic incompetence. CONCLUSION: AAIR pacing confers little benefit in sick sinus syndrome compared with AAI pacing. PMID- 8435245 TI - Abnormalities in the biosynthesis of thromboxane A2 and prostacyclin in children with cyanotic congenital heart disease. AB - BACKGROUND: Children with cyanotic congenital heart disease and pulmonary outflow tract obstruction have shortened platelet survival times and are susceptible to thrombosis and organ infarction. Thromboxane A2 and prostacyclin have opposing actions on platelet aggregability and an imbalance in their biosynthesis might contribute to the pathophysiology of these complications. METHODS: Biosynthesis of thromboxane A2 and prostacyclin was investigated in 16 children (4-32 months, median 18 months) with cyanotic congenital heart disease and pulmonary outflow tract obstruction and compared with 16 healthy children of a similar age (6-34 months, median 24 months). Urinary excretion of 2,3-dinor-thromboxane B2 (a metabolite of thromboxane A2) and of 2,3-dinor-6-oxo-prostaglandin F1 alpha (a metabolite of prostacyclin) was measured. RESULTS: The children with cyanotic congenital heart disease and pulmonary outflow tract obstruction excreted more 2,3-dinor-thromboxane B2 than the healthy children: 916(163) compared with 592(122) ng/g creatinine (mean(SEM); 2p = 0.014). The ratio of excretion of 2,3 dinor-thromboxane B2 to 2,3-dinor-prostaglandin F1 alpha was greater in the patients than in the healthy control group (2.38(0.28) v 1.3(0.22)) (2p = 0.002). CONCLUSION: The balance between biosynthesis of prostacyclin and of thromboxane A2 is abnormal in children with cyanotic congenital heart disease and pulmonary outflow tract obstruction and favours platelet aggregation and vasoconstriction. PMID- 8435246 TI - Exercise, fibrinogen, and other risk factors for ischaemic heart disease. Caerphilly Prospective Heart Disease Study. AB - OBJECTIVE: To examine the associations between physical activity and a wide range of risk factors for ischaemic heart disease including fibrinogen concentration and viscosity. DESIGN: Cross sectional evidence from the 2398 men aged 50-64 years in the Caerphilly Prospective Heart Disease Study. METHODS: Validated questionnaires were used to quantify energy expenditure on leisure activities and to grade activities related to occupation. Risk factors for heart disease examined included blood pressure, lipids, fibrinogen, and plasma viscosity. Possible confounding variables included smoking, employment, and prevalent heart disease (angina, previous myocardial infarction, and electrocardiographic evidence of ischaemia). RESULTS: Fibrinogen concentration was lower by 0.24 g/l and viscosity by 0.026 cP in the third of men who were most active in leisure activities (about 0.25 x 1 SD). A weak positive relation was found with high density lipoprotein cholesterol, but none with total cholesterol or fasting glucose concentrations or blood pressure. Triglyceride concentrations seem to be substantially lower in the most active men, although the evidence for this is not consistent. Work related activity showed relation with the lipid concentration but not with the haemostatic tests. CONCLUSIONS: Leisure activities of all levels seem to affect haemostatic and lipid factors beneficially. These effects correspond to a difference in the risk of heart disease for an active man and a sedentary man of at least 7% or 8%. Fasting triglyceride concentrations have already been shown to be strongly predictive of heart disease in this cohort of men, and the effect of exercise on this factor is also likely to confer benefit. PMID- 8435247 TI - False aneurysm of the pulmonary artery associated with cardiac catheterisation. AB - A false aneurysm of the pulmonary artery developed in a 59 year old woman as a complication of right-sided cardiac catheterisation. This rare, life-threatening condition was successfully treated with coil embolisation of the feeding artery. Cardiologists and intensive care doctors should be aware of the possibility of the formation of false aneurysms of the pulmonary artery after Swan-Ganz and other right heart catheterisation. Appropriate therapy could be life-saving. PMID- 8435248 TI - Total atrial paralysis after permanent dual chamber cardiac pacing. AB - A 73 year old woman with known ischaemic heart disease and ischaemic ventricular tachycardia underwent temporary dual chamber pacing as part of the treatment to suppress tachycardia. Insertion of a permanent dual chamber system seven days later was uncomplicated. Total atrial paralysis, with inability to pace the atrium or obtain an atrial electrocardiogram from four atrial sites, developed within 24 hours of the permanent system being implanted. Atrial electrical and mechanical function recovered over several weeks. PMID- 8435249 TI - Doppler ultrasound and the silent ductus arteriosus. PMID- 8435250 TI - Doppler ultrasound and the apparently normal heart. PMID- 8435251 TI - The laryngeal mask airway in paediatric practice. PMID- 8435252 TI - Measurement of the sensitivity of upper airway reflexes. AB - We describe a method for measurement of the sensitivity of upper airway reflexes. The technique is based upon delivery of an irritant chemical stimulus (dilute concentrations of ammonia vapour) to the upper airway. The technique is non invasive and uses equipment which is portable, allowing measurements to be made in the clinical environment. PMID- 8435253 TI - Effect of oral diazepam on the sensitivity of upper airway reflexes. AB - In a double-blind, cross-over study, we have investigated the effect of oral diazepam 20 mg and placebo on the sensitivity of upper airway reflexes in 10 male volunteers (aged 25-35 yr). Upper airway reflex sensitivity (UARS) was assessed using small concentrations of ammonia vapour as a stimulus to upper airway receptors. A threshold concentration of ammonia, at which reflex glottic closure occurred in response to the ammonia stimulus, was used as a measure of UARS. With diazepam, there was significant depression of UARS from 30 to 150 min after administration. PMID- 8435254 TI - Logistic regression analysis of fixed patient factors for postoperative sickness: a model for risk assessment. AB - One hundred and forty-seven patients undergoing minor orthopaedic surgery were studied prospectively by logistic regression analysis to determine the association of independent fixed patient factors with the incidence of postoperative sickness (nausea, retching or vomiting). Gender, history of previous postoperative sickness, postoperative opioids and interaction between gender and previous history of sickness were significant independent factors for postoperative sickness; history of motion sickness was weakly associated. The probability of postoperative sickness in the first 24 h after surgery may be estimated from the equation: logit postoperative sickness = 5.03+2.24(postoperative opioids) +3.97 (previous sickness history) +2.4 (gender) +0.78 (motion sickness) -3.2 (gender x previous sickness history). (Log likelihood ratio test for 5 degrees of freedom for the coefficients, chi-square = 53.5 (P < 0.001).) It is suggested that the calculated probability for sickness may be a useful addition for balancing patient treatment groups and allowing between-study comparisons. PMID- 8435255 TI - Comparison of automatic oscillometric arterial pressure measurement with conventional auscultatory measurement in the labour ward. AB - We have compared two non-invasive methods of arterial pressure (AP) measurement used in labour wards: an automatic oscillometric measurement obtained by Dinamap 1846, and a conventional auscultatory measurement obtained by midwives. A total of 369 AP measurements were recorded, involving 28 normotensive and hypertensive pregnant women during labour, with or without extradural analgesia. Compared with the midwife group, the Dinamap group had a greater systolic AP, by 2.7 mm Hg (P < 0.01) and smaller diastolic AP, by 9.8 mm Hg (P < 0.01). The correlations between the two methods were highly significant, but the limits of agreement were relatively wide for both systolic and diastolic AP measurements. We conclude that a clinically important difference exists in diastolic AP measurements. Dinamap diastolic AP must be corrected using a regression equation, or simply by adding 10 mm Hg, before being compared with the available normal and hypertensive AP values. PMID- 8435256 TI - Use of ultrasound to evaluate internal jugular vein anatomy and to facilitate central venous cannulation in paediatric patients. AB - Percutaneous cannulation of the internal jugular vein in paediatric patients may be technically difficult and is prone to complications. To investigate the possibility that anatomical factors contribute to these difficulties, we used a two-dimensional ultrasound scanner to examine venous anatomy in children aged up to 6 yr. We found that 18% of our children had anomalous venous anatomy that may account for some of the difficulties reported previously. The diameter of the internal jugular vein was predicted poorly by the patient's age (r2 = 0.259) or weight (r2 = 0.155). We also evaluated the use of this ultrasound scanner during percutaneous central venous cannulation in neonates and infants. Determining the course of the internal jugular vein with the scanner and then marking it on the overlying skin reduced both the time and number of needle insertions required to aspirate jugular venous blood and increased the chance of a complication-free cannulation. PMID- 8435257 TI - Metabolic effects of corrective surgery in infants and children with congenital heart defects. AB - We have measured oxygen consumption and carbon dioxide production by indirect calorimetry in 25 infants and children immediately before and after surgical correction of congenital cardiac malformations. Surgical correction of the cardiac defect caused a decrease in oxygen consumption towards normal. Greatly increased oxygen consumption values were observed before surgery in the infants with a large left-to-right intracardiac shunt and heart failure and the highest reduction in metabolic rate, up to 43%, was observed in these infants. The results indicate that corrective surgery for congenital cardiac malformations reduces the load on the cardiopulmonary system immediately after operation. PMID- 8435258 TI - Effect of nitrous oxide on cerebral blood flow in normal humans. AB - We have studied the effect of nitrous oxide on cerebral haemodynamics in 24 healthy male volunteers. Hemispherical cerebral blood flow (CBF) was measured using the xenon-133 inhalation technique, blood flow velocities in the right middle cerebral artery were calculated using transcranial Doppler ultrasound and the pulsatility index (PI)--the inverse of which is theoretically proportional to flow in the vessel under investigation--was derived from analysis of the spectrally analysed velocity pulse wave form obtained from the middle cerebral artery. Each variable was measured with the subject inhaling 100% oxygen (1st baseline), 30% nitrous oxide in oxygen, 100% oxygen (2nd baseline) and 60% nitrous oxide in oxygen. CBF was significantly greater with 30% (0.01 > P > 0.001) and 60% nitrous oxide (P < 0.001) compared with baseline, although the difference between 30% and 60% nitrous oxide was not significant. Changes in 1/PI correlated closely with those in hemispherical CBF. Blood flow velocities increased significantly with 30% (P < 0.001) and 60% nitrous oxide (0.005 > P > 0.001), the difference between 30% and 60% nitrous oxide also being significant (0.005 > P > 0.001). We observed a plateau in the change in CBF caused by nitrous oxide and suggest that this may be explained by activation of intact autoregulative mechanisms in healthy human brain. PMID- 8435259 TI - Neostigmine and edrophonium antagonism of moderate neuromuscular block induced by pancuronium or tubocurarine. AB - Edrophonium and neostigmine are anticholinesterase drugs used commonly to antagonize competitive neuromuscular block. Although it has a faster onset of action than neostigmine, edrophonium is unreliable when used to antagonize deep neuromuscular block. We have compared the antagonist characteristics of these two drugs when used to antagonize a moderate degree of pancuronium- or tubocurarine induced neuromuscular block. Forty ASA I or II patients undergoing surgical procedures were allocated randomly to receive either pancuronium 70 micrograms kg 1 or tubocurarine 0.5 mg kg-1, and to receive either edrophonium 0.5 mg kg-1 or neostigmine 0.05 mg kg-1. Antagonism was attempted when the first response to train-of-four (TOF) stimulation recovered spontaneously to 25% of the control height. Neuromuscular function was monitored using the evoked integrated electromyogram of the first dorsal interosseous muscle of the hand. Adequate recovery was defined as the achievement of a TOF ratio of 0.70 or greater. Only seven of 20 patients who received edrophonium demonstrated adequate recovery 30 min after antagonism. Under the conditions described in this study, edrophonium 0.5 mg kg-1 was less effective as an antagonist than neostigmine 0.05 mg kg-1. PMID- 8435260 TI - Tracheal intubation after induction of anaesthesia with propofol, alfentanil and i.v. lignocaine. AB - We have assessed tracheal intubating conditions in 60 ASA I or II patients after induction of anaesthesia with propofol 2.5 mg kg-1 and alfentanil 10 or 20 micrograms kg-1 with or without i.v. lignocaine 1 mg kg-1. No neuromuscular blocking agents were administered. Patients were allocated randomly to four groups: group 1 = propofol-alfentanil 10 micrograms kg-1; group 2 = propofol alfentanil 10 micrograms kg-1-lignocaine 1 mg kg-1; group 3 = propofol-alfentanil 20 micrograms kg-1; group 4 = propofol-alfentanil 20 micrograms kg-1-lignocaine 1 mg kg-1. Intubating conditions were assessed as acceptable or unacceptable on the basis of a scoring system dependent on ease of laryngoscopy, vocal cord position and coughing on insertion of the tracheal tube. Intubating conditions were acceptable in 20%, 73%, 73% and 93% of patients in groups 1-4, respectively. Intubating conditions were better and there was less coughing in the lignocaine group. PMID- 8435261 TI - Effects of intradermal lignocaine and mepivacaine on human cutaneous circulation in areas with histamine-induced neurogenic inflammation. AB - The vasoconstrictive potencies of lignocaine and mepivacaine were studied in human skin. Lignocaine 0.5%, 0.25% mepivacaine (both plain and mixed with adrenaline or ornipressin), and saline (control) were injected intradermally into skin areas with enhanced perfusion (1% histamine prick). Flux was determined by scanning laser Doppler flowmetry and the size of any eventual pallor was measured. The artificially enhanced flux was increased further by saline, but not altered by the local anaesthetics. Mepivacaine produced a small pallor. Both vasoconstrictors reduced flux significantly and produced a larger pallor. We conclude that both local anaesthetics have only a mild constrictive effect on precapillary vessels. Mepivacaine has, additionally, a constrictor effect on the postcapillary vascular bed, causing pallor. An effective precapillary constriction which reduces the capillary clearance of both local anaesthetics can be achieved only by addition of a vasoconstrictor. PMID- 8435262 TI - Anaesthesia affects plasma concentrations of vasopressin, von Willebrand factor and coagulation factor VIII in cardiac surgical patients. AB - Operative stress may affect haemostatic mechanisms through hormonal systems. As the endocrine stress response to surgery may be modulated by anaesthesia, we have altered stress hormone concentrations by using either opioid or inhalation based anaesthesia to study haemostatic mechanisms in cardiac surgical patients. Thirty patients undergoing coronary artery surgery were allocated randomly to receive fentanyl (non-stress group) or enflurane (stress group) as the main anaesthetic agent. After cardiopulmonary bypass (CPB), plasma arginine vasopressin (AVP) concentrations were significantly (P < 0.001) greater in the stress group (81.8 (46.9-142.9) pg ml-1, mean with 95% confidence limits) than in the non-stress group (5.8 (3.3-10.2) pg ml-1). Plasma noradrenaline and adrenaline concentrations increased similarly in both groups after CPB. Plasma concentrations of both von Willebrand factor (stress: 1.56 (1.33-1.79) IU ml-1; non-stress: 1.00 (0.76-1.25) IU ml-1) and coagulation factor VIII: C (stress 1.15 (0.87-1.44) IU ml-1; non-stress: 0.69 (0.55-0.80) IU ml-1) were significantly (P < 0.01) greater in the stress group than in the non-stress group after CPB. The results indicate that there is a temporal relationship between the increased plasma concentrations of AVP and von Willebrand factor and factor VIII: C. It is not clear if this indicates a causal relationship. However, variable stress control by anaesthesia may modify haemostasis in cardiac surgical patients. PMID- 8435263 TI - Effects of midazolam and flunitrazepam on the release of dopamine from rat striatum measured by in vivo microdialysis. AB - We have studied the effects of midazolam and flunitrazepam on extracellular concentrations of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in rat striatum in freely moving animals using in vivo microdialysis. I.v. injections of midazolam 0.075 and 0.15 mg kg-1 decreased striatal dopamine concentrations in a dose-dependent manner without affecting the concentrations of DOPAC and HVA. Flunitrazepam 0.015 and 0.03 mg kg-1 also decreased striatal dopamine concentrations in a dose-related manner, but the reductions in DOPAC and HVA were not significant. Flumazenil 6 micrograms kg-1 alone did not affect striatal concentrations of dopamine, DOPAC and HVA, but it prevented the effects of midazolam and flunitrazepam. Flunitrazepam 10 mumol litre-1 also decreased striatal dopamine release when infused through a dialysis probe placed into the striatum, but it failed to affect striatal dopamine release when infused into the ipsilateral substantia nigra. Central administrations of midazolam were effective only when the drug was infused into both sites simultaneously (10 and 100 mumol litre-1) or given by intraventricular injection (0.5 and 1 micrograms). These results suggest that midazolam and flunitrazepam affect striatal dopamine release in a different manner. PMID- 8435264 TI - Mathematical analysis of the upper respiratory tract from an anthropometric study. AB - In order to design a new, performed tracheal tube adapted to the shape of the upper respiratory tract, we have undertaken an anthropometric study from lateral x-rays of the neck in 130 patients with the head in a fixed position. In order to assess different clinical situations, we studied three groups of patients: group 1 = sitting, no tracheal tube; group 2 = supine, no tracheal tube; group 3 = supine, trachea intubated. We defined a standard coordinate system and determined mathematical curves for segments of the upper respiratory tract by a polynomial regression method. With these data it was possible to study the effects of physiological variations on the shape of the curves. It was then possible to determine at which region changes occur and the factors influencing these changes. We found that the relative position of the larynx was constant, whereas the hypopharynx exhibited the greatest change with the position of the head. These observations should allow us to construct a new, performed tracheal tube with elastic compliance properties to fit the changes occurring in the region of the hypopharynx. PMID- 8435265 TI - Comparison of recovery from anaesthesia induced in children with either propofol or thiopentone. AB - We studied 102 children undergoing day-case surgery, allocated randomly to receive either thiopentone 5 mg kg-1 or propofol 3 mg kg-1 i.v. at induction of anaesthesia. They then inhaled nitrous oxide and halothane in oxygen until a laryngeal mask airway could be inserted. Thereafter, halothane was substituted by isoflurane and analgesia provided by regional nerve block. Recovery from anaesthesia was assessed by the time taken to reach clinically-defined criteria and by calculation of sedation, pain and vomiting scores. In children aged less than 5 yr, only the time to spontaneous eye opening was shorter after propofol induction (P < 0.05). In children aged 5-11 yr, times of spontaneous eye opening, giving name and discharge were shorter after propofol induction (P < 0.05). These results indicate that propofol hastened early recovery in children undergoing day case surgery, but earlier discharge occurred only in older children. PMID- 8435266 TI - Plasma concentrations of bupivacaine and its enantiomers during continuous extrapleural intercostal nerve block. AB - Plasma concentrations of bupivacaine have been measured in 12 patients given bupivacaine through a paravertebral catheter placed under direct vision at thoracotomy. After an initial bolus of 0.5% bupivacaine 20 ml, mean (SEM) Cpmax was 1.45 (0.32) micrograms ml-1 and median (range) tCpmax was 25 (10-60) min. A concentration of 4.43 micrograms ml-1 measured in one patient was not associated with toxic signs. During continuous infusion of bupivacaine for 120 h, Cpmax was 4.9 (0.7) micrograms ml-1 and tCpmax 48 (5-96) h. No symptoms or signs of toxicity occurred. Separate measurement of R- and S-bupivacaine concentrations demonstrated significantly different concentration-time profiles. PMID- 8435267 TI - Long-term backache after extradural or general anaesthesia for manual removal of placenta: preliminary report. AB - A questionnaire designed to investigate the incidence of newly acquired, long term backache was sent to women who had previously undergone manual removal of the placenta during a 12-month period in one maternity hospital. There was a significantly greater incidence of long-term backache in patients who had extradural anaesthesia specifically for manual removal of the placenta compared with patients receiving a general anaesthetic for the same procedure. The results of this retrospective study in a small population warrant examination in a large, prospective, controlled investigation. PMID- 8435268 TI - Clinical evaluation of the oesophageal heat exchanger in the prevention of perioperative hypothermia. AB - We have studied the efficiency of an oesophageal warming device in the prevention of perioperative hypothermia in 22 patients undergoing total hip replacement. Aural canal and skin temperatures (15 sites) were measured before induction of anaesthesia, at the end of surgery and 1 h after recovery and mean body heat was calculated to quantify heat distribution. Core temperature decreased significantly in both groups at the end of surgery, by a mean of 1.8 degrees C in the control group and 1.3 degrees C in the oesophageal heat exchanger (treated) group (P = 0.09). In contrast, mean skin temperature at the end of surgery increased by a median value of 0.26 degrees C in the treated group and decreased by 1.02 degrees C in the control group (P = 0.03). Both groups of patients lost body heat to the same extent (P = 0.34). Thus the oesophageal heat exchanger was ineffective in preventing perioperative hypothermia in a group of patients undergoing total hip replacement. PMID- 8435269 TI - Effects of lorazepam on oxygen saturation before cardiac surgery. AB - We have studied patients presenting for coronary artery bypass surgery on two nights before surgery. Oxygen saturation during a night when the patient received no night sedation was compared with the night before surgery, when lorazepam 3-4 mg was given. There was no difference between the two nights when the total time at oxygen saturations less than 90% were compared, but the minimum oxygen saturation value when the patient received lorazepam was significantly smaller. No patient had significant sleep apnoea. PMID- 8435270 TI - Effects of midazolam on insulin secretion from isolated rat pancreatic islets of Langerhans. AB - Isolated, cultured rat pancreatic islets of Langerhans were incubated in medium containing glucose 2 or 20 mmol litre-1 and with glucose supplemented with midazolam 10, 100 or 1000 ng ml-1. Glucose 20 mmol litre-1 with the addition of noradrenaline 10 mumol litre-1 was used as a control. In contrast with noradrenaline, midazolam did not inhibit glucose-induced insulin secretion. Noradrenaline 10 mumol litre-1 inhibited secretion to basal values in response to glucose 20 mmol litre-1 (P < 0.001). PMID- 8435271 TI - Visualization of extradural blood patch for post lumbar puncture headache by magnetic resonance imaging. AB - We describe a case of post lumbar puncture headache treated by extradural blood patch. Magnetic resonance imaging (MRI) demonstrated a large extradural haematoma extending over four spinal segments and extending out through the neural outlet foramina. There was significant compression of the thecal sac, supporting the theory that extradural blood patch causes tamponade at the site of dural puncture. The spread of clot was predominantly upwards from the injection site and subarachnoid extension of blood was also demonstrated. PMID- 8435272 TI - Muscular paralysis and ventilatory failure caused by hyperkalaemia. AB - We report the history of a diabetic man presenting with hyperkalaemia and rapidly progressing muscular paralysis with severe respiratory embarrassment. His symptoms resolved rapidly with reduction of the serum potassium concentration. Similar cases have been reported previously but this is a problem that few will have encountered and is a diagnosis which should not be overlooked before artificial ventilation is commenced. PMID- 8435273 TI - John Henry Hill Lewellin: the first etherist in Glasgow. AB - John Henry Hill Lewellin, a surgeon-dentist, was the first to administer ether in Glasgow, on January 4, 1847. He was born in Calcutta, trained at St Bartholomew's Hospital, qualified M.R.C.S. in London in 1842, and studied in Paris and Heidelberg, before moving to Glasgow in December 1845. He remained there for about 18 months, advertising his dental practice in a high profile manner and, when the time came, he publicized his experience with ether in the local press in an exemplary way. He disappeared from Glasgow in June 1847, and reappeared in Australia 5 years later, practising as a dentist initially, and later as a general medical practitioner in Melbourne until his retirement in 1883. He died in 1886. PMID- 8435274 TI - Neuromuscular blockers in day-case surgery: is speed of onset more important than duration of action? PMID- 8435275 TI - Metabolic effects of dobutamine. PMID- 8435276 TI - Metabolic effects of dobutamine. PMID- 8435277 TI - Nitrous oxide administration via oxygen therapy devices. PMID- 8435278 TI - Mortality in ITU patients receiving neuromuscular blocking drugs. PMID- 8435279 TI - Pain on i.v. injection of metoclopramide. PMID- 8435280 TI - Assessing trolley and table products. PMID- 8435281 TI - Keeping the pressure high on prevention. AB - Health care professionals have long recognised pressure sores as a problem (1, 2, 3). Attention has focused on the monetary cost and scale of the issue (4) in terms of pain caused and competition for finite resources (5). The Health of the Nation consultative document (6) estimated that 6.7 per cent of the adult hospital population are affected, costing the NHS at least 60 million pounds a year. Many consider these sores preventable, and believe the deployment of resources in the health service should focus on prevention instead of treatment (7). PMID- 8435282 TI - Vasculitic Syndromes. PMID- 8435283 TI - Miscellaneous neurologic, cardiac, pulmonary, and metabolic disorders with rheumatic manifestations. AB - Problems both old and new are featured in this year's selection of rheumatologic aspects of miscellaneous diseases. Paralysis of one or more limbs can lead to many musculoskeletal complications, and the approach of Auguste Dejerine-Klumpke in 1918 can be compared with that of the present-day physician. The reappearance of rheumatic fever continues to excite interest. The specificity of the modified Jones criteria has been questioned, as have the benefits of long-term antibiotic prophylaxis following an attack of the disease. Meanwhile, metabolic disorders may be the first diseases to come under novel scrutiny using the techniques of genetic engineering, with outstanding possibilities for advancing both understanding and treatment. Dermatologic diseases other than psoriasis may be associated with arthropathy. Many of these symptom complexes may be variants of the recently described SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome. PMID- 8435284 TI - Wegener's granulomatosis. AB - In recent years, interest in Wegener's granulomatosis has been stimulated by an increasing appreciation of the chronic relapsing nature of this disease and its association with antibodies to proteinase 3. Although conventional therapy with cyclophosphamide and glucocorticoids has produced remission in most patients, remission may not occur immediately and, in at least 50% of patients, may be followed by relapse. As a result, most patients experience some form of permanent morbidity from disease or treatment, or both. These observations have led to renewed efforts to identify more effective and less toxic therapies. Preliminary studies have evaluated other cytotoxic agents, such as methotrexate, and biologic products, such as high-dose immunoglobulin and monoclonal antibodies. It is hoped that a better understanding of the possible pathogenic role of anti-proteinase 3 antibodies may contribute to improved therapy. Unfortunately, research is handicapped by lack of an animal model, without which it will be difficult to prove convincingly that anti-proteinase 3 antibodies are important in expressing disease. PMID- 8435285 TI - Value of tests for antineutrophil cytoplasmic autoantibodies in the diagnosis and treatment of vasculitis. AB - The diagnosis and classification of vasculitis has been revolutionized by the discovery and characterization of serum antineutrophil cytoplasmic autoantibodies. These autoantibodies are highly specific, objective markers for the major subset of vasculitis that includes Wegener's granulomatosis, polyarteritis nodosa (microscopic polyangiitis), Churg-Strauss syndrome, primary or idiopathic pauciimmune necrotizing and crescentic glomerulonephritis with or without pulmonary hemorrhage, as well as some poorly characterized and overlapping forms of these vasculitides. The finding of antineutrophil cytoplasmic antibodies throughout this group identifies these syndromes as a single category or spectrum of disease. The sensitivity of antineutrophil cytoplasmic antibodies for this group of conditions is high when there is systemic involvement, as defined by the presence of renal involvement. However, the antibodies are only moderately sensitive markers in limited or localized cases of these vasculitides (without renal involvement), and hence diagnosis of these conditions based on histologic and clinical criteria remains important. Two significant types of antineutrophil cytoplasmic antibodies have been identified: anti-proteinase 3 and antimyeloperoxidase antibodies. Both have proven to be of diagnostic value for the spectrum of vasculitis listed above. Remarkably, patients with this spectrum of vasculitis have only one or the other of these two types of antibodies. PMID- 8435286 TI - Cutaneous vasculitis and other neutrophilic dermatoses. AB - During 1991 and 1992 there was an abundance of articles dealing with vasculitis and its cutaneous manifestations, as well as with the perhaps related disorders known as neutrophilic dermatoses. This brief review will deal with some of the more controversial areas. The specific issues discussed are those relating to the "new" American College of Rheumatology classification system and its application to patients who have skin lesions of vasculitis, the recently associated diseases, and the newer therapies for vasculitis. In addition, recent publications regarding acute neutrophilic dermatosis (Sweet's syndrome) and pyoderma gangrenosum are briefly discussed. PMID- 8435287 TI - Kawasaki disease. AB - Kawasaki disease is an acute vasculitis of young children that is complicated by the development of myocarditis and coronary artery abnormalities. Recent studies indicate that the prevalence of cardiovascular abnormalities can be significantly reduced by treating patients during the first 10 days of illness with high-dose intravenous gammaglobulin, particularly at a dose of 2 g/kg. Thus, early recognition and prompt treatment of this illness is critical for a successful outcome. This process would undoubtedly be facilitated if the etiologic agent or toxin that causes Kawasaki disease were known. In this regard, studies of the past year strongly suggest that a superantigen plays an important role in stimulating the massive immune activation associated with this illness. These observations may provide an important new direction for investigations into the etiology and pathogenesis of Kawasaki disease. PMID- 8435288 TI - Systemic vasculitic syndromes. AB - The current lack of knowledge about the factors underlying both the etiopathogenesis and extent of the clinical expression of necrotizing vasculitis is illustrated by recent articles. "Benign" vasculitis may present as localized disease in skin, gut, or even muscle; but on long-term follow-up, systemic involvement frequently occurs. Exciting studies on the occurrence of viruses such as hepatitis C in vasculitis compound these problems, because they are associated with multiple syndromes and the mechanism underlying their relationship to vasculitis remains to be elucidated. Further subdivision of antineutrophil cytoplasmic antibodies may aid in classification, but currently, their association with disease activity and extent obscures that role. Age is also less useful, because Kawasaki syndrome may occur rarely in adults and polyarteritis nodosa was reported in a large series of children. Differentiation is important because of the various responses to therapy. The first controlled study of cyclophosphamide as therapy for necrotizing vasculitis confirms its early benefit but, interestingly, shows no difference in 10-year survival rates. The addition of plasma exchange is of benefit only in the small number of patients with severe renal involvement who are dialysis-dependent at onset. PMID- 8435289 TI - Miscellaneous vasculitic syndromes including Behcet's disease and central nervous system vasculitis. AB - Behcet's disease is a chronic, relapsing, inflammatory process with clinical features of aphthous oral and genital ulcerations, uveitis, cutaneous vasculitis, arthritis, and central nervous system involvement. Large-vessel vasculitis, thrombophlebitis, and gastro-intestinal ulcerations may occur. As in other rheumatologic diseases, a genetic predisposition coupled with a triggering event leads to alterations in immune function and response, with variable clinical disease manifestations. Mononuclear cell activation and cytokine release, neutrophil chemotaxis, and humoral immune response with elevations of circulating immune complexes contribute to the pathogenesis of Behcet's disease. Vasculitis and vascular involvement are highlighted. There is no single diagnostic test for Behcet's disease. Treatment is comprised of anti-inflammatory and immunosuppressive agents and, in selected individuals, anticoagulation. Isolated central nervous system vasculitis or noninfectious primary (granulomatous) angiitis of the central nervous system is reviewed briefly. This condition is rare, predominantly affects young women, and includes symptoms of headache, weakness, and confusion. Characteristically, erythrocyte sedimentation rate is normal, serologic studies are negative, and cerebral angiography shows multifocal and segmental vascular narrowing and beading. Typical histopathology is granulomatous in less than 50% of patients, followed by necrotizing or lymphocytic vasculitis, or both, often with thrombosis. Treatment with immunosuppressive agents improves symptoms and outcome. PMID- 8435290 TI - Systemic disorders with rheumatic manifestations. PMID- 8435291 TI - Advances in amyloidosis. AB - Major advances of the past year in the amyloidoses include a better understanding of the polymorphism of the acute-phase reactant serum amyloid A protein and the appearance of a new mouse model for primary amyloidosis. The list of single point mutations in transthyretin in different families with slightly varied clinical manifestations of the disease continues to grow. Gelsolin, with its asparagine 187 mutation, was found to cause amyloidosis beyond the borders of Finland, where it has been extensively evaluated. The incredible range of osteoarticular lesions due to beta 2-microglobulin in hemodialysis amyloidosis continues to expand and includes severe manifestations of spondyloarthropathy. The greatest number of papers in the amyloid literature have involved amyloid beta protein, amyloid beta protein precursor associated with Alzheimer's disease, and prion protein associated with the spongiform encephalopathies. The widespread systemic involvement of amyloidosis has led to the appearance of a host of manifestations, some common and some rare. Treatment advances focus on the use of liver transplantation in familial amyloid polyneuropathy to remove the source of mutant protein synthesis. PMID- 8435292 TI - Renal disease and rheumatic manifestations. AB - Renal disease has long been recognized as a cause of rheumatic complaints. With the advent of renal replacement therapy, whether dialysis or renal transplantation, the older problems have been supplanted by a new generation of disorders, affecting bone, joints, and soft tissues. This review includes a discussion of recent surveys identifying a high prevalence both of ligamentous laxity in transplant patients and dialysis-associated arthropathy in long-term dialysis patients. Also discussed are studies investigating the natural history of early posttransplant avascular necrosis. PMID- 8435293 TI - Gastrointestinal disorders and rheumatic diseases. AB - Although we continue to learn more about the persistence of bacterial antigens in patients with HLA-B27, the significance of this persistence in the pathogenesis of the spondyloarthropathies remains unclear. The role of dietary antigen exposure and the ability of true food allergy to produce rheumatic complaints is even less definite, although most authors now agree that dietary manipulation using allergen-free or allergen-restricted diets may benefit a small number of patients with rheumatic disease complaints. Dietary manipulation substituting omega-3 for omega-6 fatty acids, however, is frequently beneficial to rheumatoid patients. Is this the way of the future? It is certain that dietary manipulation is less toxic than the standard therapies. It is also certain that we cannot guarantee that any standard therapy will work, except perhaps for prednisone administration. We really have nothing to lose by pursuing this therapeutic approach, and I am surprised that although we have become very diet conscious, dietary manipulation as therapy for patients with rheumatic diseases continues to be underinvestigated, particularly in systemic lupus erythematosus and Sjogren's syndrome. PMID- 8435294 TI - Endocrine disease. AB - The effects of endocrine disease on bone mass continue to attract attention. Investigations include the effects on the skeleton of thyroid disease, primary hyperparathyroidism, and their treatment. The effect of growth hormone replacement in adults with panhypopituitarism has also been investigated; children with treated growth hormone deficiency appear to reach adulthood with low bone mass. The indications for surgery in asymptomatic primary hyperparathyroidism have recently been reviewed. The associations between autoimmune thyroid disease and connective tissue disease have been investigated. Although patients with Graves' disease are frequently positive for antinuclear antibodies, there appears to be no increased risk of systemic autoimmune disease. The possible pathogenesis of diabetic bone disease via calcium malabsorption, hypercalciuria, reduced bone formation, and collagen abnormalities has been reviewed. A long-term study has clarified the links among diabetic control, limited joint mobility, nephropathy, and retinopathy. The possible mechanisms by which pregnancy may induce remission in rheumatoid arthritis have been discussed. PMID- 8435295 TI - Immunopathology, musculoskeletal features, and treatment of sarcoidosis. AB - Sarcoidosis is a clinical expression of intricate immune events. Firm evidence exists that unchecked helper T-cell proliferation restricted to the site of disease activity is the pivotal aberration. Alveolar macrophages from patients with sarcoidosis have been observed to release high levels of tumor necrosis factor-alpha and interleukin-2 and to exhibit enhanced expression of leukocyte function antigen 1 and intercellular adhesion molecule 1. These cytokines and adhesion molecules could result in compartmentalized T-cell proliferation at certain sites of disease. A new marker, serum procollagen type III-derived peptide, is reported to correlate with disease activity. Arthrosonography revealed periarticular edema as the prime pathologic process in the acute sarcoid reaction. Magnetic resonance imaging has greater diagnostic utility than does computed tomography in sarcoid myopathy. The acute sarcoid reaction is associated with a distinct HLA type and resolves spontaneously in 1 to 6 months. Chronic sarcoid arthritis causes destructive and deforming changes that rarely can be akin to Jaccoud's type arthropathy. Muscle and osseous disease is rare and asymptomatic. Nonsteroidal anti-inflammatory drugs and corticosteroids are the mainstays of pharmacotherapy. Deflazacort is an effective and safe steroid preparation with a lesser incidence of osteoporosis when used for long periods. PMID- 8435296 TI - Sickle-cell disease, hemophilia, and hematology. AB - Primary hematologic disorders and the hematologic problems associated with systemic rheumatologic disease have widespread and significant implications for the clinical management of rheumatic disease. This article reviews recently published information on the epidemiology, pathophysiology, and management of hemoglobinopathies, hemophilia, and other hematologic pathologies associated with significant rheumatologic manifestations. PMID- 8435297 TI - Rheumatic manifestations of neoplasia. AB - Recent literature on the rheumatic manifestations of neoplasia has again focused on the increased association of Sjogren's syndrome and rheumatoid arthritis with lymphoproliferative malignancies and leukemias. A series of 13 patients with monocytoid B-cell lymphoma, a recently described variant of low-grade B-cell lymphoma, and Sjogren's syndrome was reported. The skeletal manifestations of leukemias are extensively reviewed emphasizing that osteoarticular manifestations may predate the hematologic disease. A case of monoarthritis of the knee as a manifestation of chronic leukemia is presented in which synovial biopsy revealed a leukemic infiltrate. Recent studies looking at the association of polymyositis and dermatomyositis with malignancy challenge this link. Two cases of malignancy presenting with polyarthritis are reviewed, and in both cases the polyarthritis resolved with removal of the tumor. A case report and a series of synovial sarcomas are also reviewed. Hodgkin's disease can initially present with skeletal involvement; six cases are reviewed. PMID- 8435298 TI - Recommended composition of influenza virus vaccines for use in the 1993-1994 season. PMID- 8435300 TI - Influenza. PMID- 8435299 TI - Injury prevention. Public health approaches to improved road safety. PMID- 8435301 TI - Continuing care: keeping on the right track. Interview by Charlotte Alderman. PMID- 8435302 TI - Women's issues. Still battling on. Interview by Norah Casey. PMID- 8435303 TI - Nurses work. The campaign begins. PMID- 8435304 TI - Nurses work. Fear at the cutting edge. PMID- 8435305 TI - Nurses work. No job for life. PMID- 8435306 TI - Preparing RNMH tutors for P2000. PMID- 8435307 TI - CPR: the problems and solutions. PMID- 8435308 TI - Posting notice about skill mix exercises. PMID- 8435309 TI - Formal measurement of pain by nurses. AB - How often have we heard nurses complain because doctors have not prescribed adequate pain relief for patients? Nurses, however, are just as guilty as doctors of not managing patients with acute and chronic pain adequately. Concern that nurses in her district were not using, or were using inappropriately, pain assessment tools prompted the author to undertake a small survey of current practice. The results confirmed her suspicions, but subsequent continuing education programmes on pain management seem to be helping to raise nurses' awareness of their responsibilities in this crucial area of care. PMID- 8435310 TI - Community nursing: ruff stuff in the community. PMID- 8435311 TI - Diabetes: just hypochondria? PMID- 8435312 TI - Quality care. Abortion: no middle ground. PMID- 8435313 TI - Childcare nursing: the faltering first steps. PMID- 8435314 TI - A vote for women. PMID- 8435315 TI - Psychiatric nurses go mental. PMID- 8435316 TI - Effects of vitamin K and oral anticoagulants on urinary calcium excretion. AB - In a subgroup of postmenopausal women vitamin K induced a decrease of the urinary calcium loss. This effect was significant (P < 0.0001) in the so-called fast losers of calcium (calcium/creatinine ratio > 0.5). To find out whether vitamin K antagonists would have an opposite effect, a study was started among 141 persons on long-term oral anticoagulant therapy. In this population the number of fast losers was recorded, and compared to that in a group of age- and sex-matched non treated controls. Notably in young men the fraction of fast losers was significantly higher in the anticoagulant-treated group than in the control group (25 v 0%, P < 0.02). Differences between treated and nontreated groups may also be found in other markers for calcium and bone metabolism, notably in serum osteocalcin concentration and in urinary hydroxyproline excretion. The conclusion of our study is that oral anticoagulant treatment must be regarded as a potential risk factor for a high loss of urinary calcium. PMID- 8435317 TI - Rapid analysis of -alpha 3.7 thalassaemia and alpha alpha alpha anti 3.7 triplication by enzymatic amplification analysis. AB - In this report we describe a PCR-based method for the diagnosis of the most common form of alpha thalassaemia, the -alpha 3.7 deletion which occurs throughout all tropical and subtropical regions of the world. The same procedure also identifies the reciprocal recombinant chromosome (alpha alpha alpha anti 3.7). Restriction mapping of the PCR products has enabled us to distinguish between the type I (-alpha 3.7 I), type II (-alpha 3.7 II) and type III (-alpha 3.7 III) deletions. This strategy will be very useful in screening programmes of alpha thalassaemia occurring on its own or in association with beta thalassaemia and sickle cell disease. PMID- 8435318 TI - Molecular basis and haematological characterization of beta-thalassaemia major in Taiwan, with a mutation of IVS-1 3' end TAG-->GAG in a Chinese patient. AB - We studied 41 patients with beta-thalassaemia major and their parents by using a combination of polymerase chain reaction (PCR) amplification, slot-blot hybridization of allele-specific oligonucleotide (ASO), and direct genomic sequencing. Eight different point mutations were characterized. C to T substitution at nucleotide (nt) 654 of intervening sequences (IVS) 2, accounting for 46.3% of mutant beta-globin genes, is the most common mutation in Taiwan, followed by frameshift codons 41/42 with four nucleotides (TCTT) deletion for 31.7%, A to G substitution at position -28 of promotor area for 8.5%, A to T substitution at codon 17 for 6.1%, frameshift codons 27/28 (insertion of C) for 2.4%, G to T substitution at nucleotide 1 of IVS-1 for 2.4%, frameshift codons 71/72 (insertion of A) and IVS-1 3 end TAG-->GAG for 1.2%. The former four mutations showed no obvious difference between two major ethnic groups in Taiwan. As to mutations in each individual of beta-thalassaemia major, the incidence of compound heterozygotes of two different mutations is much higher than homozygotes of single mutation, 78.0% v 22.0%. Compound heterozygotes of C to T substitution at nt 654 of IVS-2 and frameshift codons 41/42 with four nucleotides deletion is the most common pattern of beta-thalassaemia mutations in each individual (41.5%). The results are somewhat different from other documented reports concerning the mutations of beta-thalassaemia in southern China. This is the first report of mutation of IVS-1 3' end TAG-->GAG which causes consensus change in Chinese people. Patients with heterozygotes of beta zero and -28 beta(+) thalassaemia mutations would have a greater delay in initial transfusion in comparison to patients with homozygotes of both beta zero-thalassaemia mutation, but their initial clinical manifestation might be aggravated when combined with a glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and an insult such as exposure to infection and certain drugs. PMID- 8435319 TI - Age dependency of red blood cell deformability and density: studies in transient erythroblastopenia of childhood. AB - Several investigators have demonstrated that red blood cell (RBC) deformability decreases progressively with increasing cell density and proposed that reduction in deformability plays a role in the senescence process of normal RBCs. Transient erythroblastopenia of childhood (TEC) results from temporary cessation of erythropoiesis. Since no new RBCs are produced for some time, the circulating RBCs are relatively old. RBS density (phthalate-oil method) and RBC deformability (RBC elongation in a counter-rotating rheoscope) were studied in seven children with TEC and in 10 control children. The mean values of MCHC, RBC density and RBC deformation were not significantly different between TEC and control children. Compared to controls, the frequency distribution of RBC density in TEC was slightly shifted to higher values. The percentage of RBCs with extremely low densities (< 1.090 g/ml) was 0.9 +/- 1.2% in the patients and 5.6 +/- 2.3% in the controls (P < 0.001). The percentage of RBCs with high density (> 1.106 g/ml) was 6.4 +/- 2.1% in the patients and 4.9 +/- 1.8% in the controls (P > 0.10). The reduction of RBCs with low density in TEC suggests that RBCs with low density are relatively young. Since the percentage of RBCs with high density increased only slightly in TEC, we conclude that only a fraction of dense RBCs is old. In TEC, the frequency distribution of RBC elongation was slightly shifted to lower values. 5% of the RBCs studied in the control children had RBC elongation values above 0.39 (TEC 1.2%) and 5% had elongation values below 0.16 (TEC 6.7%). Thus, only a small fraction of highly deformable RBCs was diminished in TEC. These data suggest that a decrease in deformability is not a significant part of the normal ageing process of human RBCs. PMID- 8435320 TI - The effect of endotoxin and tumour necrosis factor on erythrocyte and leucocyte deformability in vitro. AB - Microcirculatory disorders are a common finding in sepsis. We have analysed the influence of two factors released in sepsis, endotoxin and tumour necrosis factor (TNF), on rheological properties of blood cells. The deformability of mixed cell suspensions, isolated erythrocytes, mononuclear cells, or polymorphonuclear leucocytes exposed to endotoxin and TNF in vitro was assessed by filtration through pores of different sizes. Mixed blood cell suspensions showed an increase in cell rigidity when incubated with 100 ng/ml endotoxin. The filtration resistance of isolated erythrocytes, mononuclear or polymorphonuclear leucocytes was not affected by endotoxin. Incubation with TNF in physiological concentrations increased the rigidity of mixed blood cells and of isolated polymorphonuclear leucocytes in a dose- and time-dependent manner, while erythrocytes and mononuclear leucocytes remained unaffected. Polymorphonuclear cells showed decreased deformability associated with shape changes (polarized and non-polar cells with surface protrusions and a shift of F-actin into protrusions). The decrease in deformability was reversed by cytochalasin B or xanthin derivatives such as pentoxifylline. We conclude that TNF decreases the passive deformability of polymorphonuclear leucocytes, which may affect the microcirculation in sepsis. The reversibility with xanthin derivatives may represent a new therapeutic approach for the high morbidity and mortality in sepsis. PMID- 8435321 TI - Erythrocyte haemolysate interacts with ATP-Fe to form a complex containing iron, ATP and 13 800 MW polypeptide. AB - Iron first entering the reticulocyte is bound to ATP in the low MW cytosolic pool; some is also 'loosely bound' to haemoglobin, coeluting with haemoglobin from a molecular sieve column though not incorporated into haem. When haemolysate is mixed with ATP-Fe in vitro a similar high MW iron-containing complex is formed: the ATP-Fe interacts with a non-haemoglobin constituent of the haemolysate to form a high MW ATP-Fe complex in which the ratio of ATP:Fe (originally 6:1) is reversed, so that the complex contains more iron than ATP. The high MW ATP-Fe complex is formed even when ATP is in 150-fold molar excess and is formed without detectable hydrolysis of the ATP. The activity of haemolysate in forming the high MW ATP-Fe complex is not diminished by dialysis; all of the activity is recovered in the haemoglobin-containing fraction obtained from an Ultrogel AcA 44 column. The activity does not derive from haemoglobin since 85% of the activity is removed when haemoglobin is purified from haemolysate with DEAE-Sephadex. The chelatable iron pool of the cell probably includes both the high MW ATP-Fe complex and low MW ATP-Fe. Shunting of ATP-Fe to a high MW aggregate reduces the amount of iron present in the highly reactive low MW form and thus probably serves to limit the formation of cell damaging radicals. PMID- 8435322 TI - Reduced responsiveness of bone marrow megakaryocyte progenitors to platelet derived transforming growth factor beta 1, produced in normal amount, in patients with essential thrombocythaemia. AB - In this study we evaluated the amount of transforming growth factor-beta 1 (TGF beta 1) in platelet lysates obtained from 12 patients affected by essential thrombocythaemia (ET) in comparison with five patients affected by myelofibrosis with myeloid metaplasia (MMM) and 15 healthy donors. The levels of both bioactive and latent TGF-beta 1, evaluated in a bioassay on CCL64 cells, before and after transient acidification, were similar in platelet lysates from ET patients and normal donors and significantly (P < 0.01) elevated in platelet lysates from MMM patients. Moreover, platelet lysates from ET patients and normal controls, showed a similar degree of colony suppression when tested on haematopoietic progenitor (CD34+) cells, purified from normal bone marrows, whereas platelet lysates from MMM patients showed a higher (P < 0.01) inhibitory activity on normal CFU-meg and BFU-E growth. In parallel, platelet lysates form ET patients and normal controls were tested on CD34+ cells, purified from ET bone marrows. ET bone marrow BFU-E, similarly to normal bone marrow BFU-E, were markedly inhibited by platelet lysates, whereas ET bone marrow CFU-meg were significantly (P < 0.05) less responsive to the inhibitory activity of platelet lysates than normal bone marrow CFU-meg. The main factor responsible for the inhibitory activity contained in platelet lysates was transforming growth factor-beta 1 (TGF-beta 1), as demonstrated by the ability of a polyclonal neutralizing anti-TGF-beta 1 antibody to almost completely reverse the suppressive effect of platelet lysates on CFU meg and BFU-E growth. Our data demonstrate that the amount of intraplatelet TGF beta 1 is similar in ET patients and normal controls, whereas it is increased in platelets from MMM patients. Moreover, megakaryocyte progenitors in ET show a reduced sensitivity to platelet-derived inhibitors and, in particular, to TGF beta 1. PMID- 8435323 TI - Treatment of aplastic anaemia (AA) with antilymphocyte globulin (ALG) and methylprednisolone (MPred) with or without androgens: a randomized trial from the EBMT SAA working party. AB - 134 patients with acquired aplastic anaemia (AA) were given HALG 15 mg/kg/d for 5 d and methylprednisolone for 1 month, and randomized to receive (n = 69) or not (n = 65) oxymetholone 2 mg/kg/d p.o. daily for 4 months. Early mortality (< 120 d) was comparable in the two arms 12/69 (17%) and 11/65 (17%), and correlated with the severity of the disease (39%, 10% and 6% respectively in patients with neutrophil counts (PMN) < 0.2, 0.2-0.5, > 0.5 x 10(9)/l). The response rate at 120 d was significantly greater in patients receiving androgens (56% v 40%; P = 0.04); it was 68% v 48% (P = 0.02) in patients surviving 120 d, and 78% v 27% (P = 0.03) in females with PMN less than 0.5 x 10(9)/l. In a multivariate Cox analysis on patients with less than 0.5 x 10(9)/l PMN, the probability of responding without androgens was reduced compared to the androgen treatment arm (P = 0.05). Survival was comparable in the two groups (71% v 65%). It was superior (74% v 50%), but not significantly (P = 0.1) in females with PMN < or = 0.5 x 10(9)/l receiving androgens. Side-effects, including biochemical abnormalities and virilization, could be controlled and were reversible. In conclusion, the addition of androgens to HALG and methylprednisolone as first line treatment of aplastic anaemia significantly improves the response rate at 4 months, particularly in females with low neutrophil counts, although there is no significant effect on short-term survival. The reversible side-effects warrant the use of androgens as an adjunct to the first course of ALG in females with severe AA. PMID- 8435324 TI - Severe poikilocytosis associated with a de novo alpha 28 Arg-->Cys mutation in spectrin. AB - Severe poikilocytosis was observed in an Italian child. The mutation responsible was a de novo alpha 28 Arg-->Cys substitution (CGT-->TGT) in spectrin, a mutation known to cause hereditary elliptocytosis or hereditary pyropoikilocytosis. In this particular case the severity of the manifestations were accounted for by the occurrence, in trans to the alpha 28 mutation, of the alpha V/41 polymorphism. The latter has been shown previously to be associated with structural abnormalities at the alpha IV-alpha V domain junction and with a low expression level. The pronounced alteration of the dimer self association process was also explained by the location of the alpha 28 mutation. This mutation occurs in helix 3 of repeating segment alpha 1, e.g. precisely in the head-to-head contact between the spectrin alpha and beta chains. The present phenotype was compared to that yielded by another alpha 28 mutation (Arg-->His) also combined, in trans, with the alpha V/41 polymorphism. The pictures were very much alike, stressing the functional importance of residue alpha 28. The de novo character of the present mutation strengthens the view that codon alpha 28 is a 'hot spot' for mutations. PMID- 8435325 TI - Clinical, haematological and cytogenetic features in 24 patients with structural rearrangements of the Q arm of chromosome 3. AB - To determine the frequency and clinical significance of acquired abnormalities of chromosome 3 at q21 and q25-26 in haematological malignancy, we reviewed the haematological and cytogenetic features of 24 patients with a 3q rearrangement identified amongst 1200 cases with clonal cytogenetic abnormalities detected at our institutions during a 12-year period. Thirteen patients presented with de novo acute myeloid leukaemia (AML), 10 with myelodysplasia (MDS) and one in blast phase of chronic myelogenous leukaemia. Twenty patients (83%) had megakaryocytic dysplasia and 14 (58%) had normal or increased numbers of megakaryocytes, but only four patients (16%) had absolute thrombocytosis > 500 x 10(9)/l (three with AML, one with MDS transforming to AML). A review of 205 cases of AML investigated in our institutions between 1985 and 1990 for whom cytogenetic results were obtained revealed that a platelet count > 500 x 10(9)/l at presentation was highly suggestive of an underlying 3q abnormality. A limited review of the literature on this subject confirmed that 15-20% of patients with a 3q abnormality will have thrombocytosis. The response of these patients to conventional antileukaemic therapy is uniformly poor, despite haematological and clinical differences between the subtypes of 3q rearrangements. PMID- 8435326 TI - Acquired sideroblastic anaemia during treatment of Wilson's disease with triethylene tetramine dihydrochloride. AB - We report one case of acquired sideroblastic anaemia in a patient treated for Wilson's disease with triethylene tetramine dihydrochloride (TTH). No other cause of acquired sideroblastic anaemia was found, and neither iron nor pyridoxine therapy could correct this anaemia. In contrast, decreasing the dose of TTH led to disappearance of ringed sideroblasts. Thus TTH should be added as a further cause of secondary acquired sideroblastic anaemia. The pathophysiology of this finding, probably linked to an abnormality of mitochondrial iron metabolism, is briefly discussed. PMID- 8435327 TI - Successful immunosuppressive treatment after failure of erythropoietin therapy in two subjects with refractory anaemia. PMID- 8435328 TI - Detectability of immunoglobulin and c-myc gene rearrangements in multiple myeloma. PMID- 8435329 TI - Red cell macrocytosis and chronic obstructive airways disease. PMID- 8435330 TI - t(8;9) in chronic myeloid leukaemia. PMID- 8435331 TI - Increase of gamma/delta T cells in a case of typhoid fever. PMID- 8435332 TI - Cyclosporine therapy for Langerhans cell histiocytosis. PMID- 8435333 TI - Resolution of transfusion dependence by recombinant human erythropoietin (rHuEPO) in acquired pure red cell aplasia (PRCA) associated with myeloid metaplasia. AB - A patient with acquired pure red cell aplasia and agnogenic myeloid metaplasia (AMM) was treated with rHuEPO. She became transfusion independent. Weekly injections of rHuEPO have maintained the response without side-effects or disease progression. In addition, marrow fibrosis and splenomegaly have decreased. Therefore, rHuEPO may be effective therapy for some patients with acquired PRCA and/or AMM. PMID- 8435334 TI - Antibody By114 is selective for the 90 kD PI-linked component of the CD66 antigen: a new reagent for the study of paroxysmal nocturnal haemoglobinuria. AB - This paper describes a monoclonal antibody which reacts with transfected cells carrying a gene (NCA-50/90) which has been shown to encode the human CD66 antigen. However, antibody By114 recognizes only a single 90 kD polypeptide from human neutrophils, whereas the antibodies which originally defined the CD66 antigen also recognize a larger 180-200 kD protein. We conclude that antibody By114 is selective for the smaller of the two CD66 gene products, which is a surface membrane phosphatidyl-inositol (PI)-linked molecule. The reactivity of antibody By114 on peripheral blood cells (positive on neutrophils, weak or negative on eosinophils, and negative on basophils, monocytes and lymphocytes) and myeloid precursor cells was identical to those of a reference CD66 antibody, as was the staining of leukaemic cells. However, the reactions of the two antibodies differed on kidney, liver and pancreas, and in cases of myeloma, Waldenstrom's macroglobulinaemia and lymphoma, indicating that By114 represents a new CD66 sub-specificity. Granulocytes from a case of paroxysmal nocturnal haemoglobinuria (PNH) were negative with antibody By114, indicating that it may be of value in detecting the defect in PI-linked surface molecules characteristic of this condition. Antibody By114 also stained formalin fixed paraffin embedded tissues and may therefore be of use in routine diagnostic histopathology. PMID- 8435335 TI - Quantification of leukaemic cells based on heteroduplex formation of tal-1 gene sequences after PCR coamplification. AB - Based on the high sensitivity of the polymerase chain reaction (PCR) several assays have already been described which can be applied to monitor minimal residual disease in patients with leukaemia. However, most of these approaches are only qualitative or semiquantitative at best. Moreover, the semiquantitative assays require rather large-scale procedures such as oligonucleotide hybridization or sampling of aliquots during the exponential phase of PCR amplification, which is time consuming and may be error prone. Using the deletion in the tal-1 gene as a clonal marker of malignant cells, which can be found in about 10-25% of T-cell acute lymphoblastic leukaemia, we have developed a rapid and simple PCR assay for the quantification of residual leukaemic cells. The assay is based on heteroduplex formation between standard and template DNA sequences after coamplification of both DNA sequences in the same PCR reaction. The sensitivity of this PCR approach allows the detection of neoplastic cells at frequency of at least 10(-4). Application of such an assay needs not to be restricted to patients harbouring a tal-1 gene deletion. It may easily be adapted to other clonal DNA markers of blast cells and therefore facilitate monitoring of minimal residual disease in many different kinds of leukaemia. PMID- 8435337 TI - Consistent involvement of the 3' half part of the first BCR intron in adult Philadelphia-positive leukaemia without M-bcr rearrangement. AB - About one half of Philadelphia (Ph)-positive acute leukaemia (AL) patients and rare cases of Ph-positive chronic myelogenous leukaemia (CML) show rearrangements within the first intron of the BCR gene on chromosome 22. We studied breakpoints within the first BCR intron in 22 adult patients with Ph-positive leukaemia; 21 with AL and one with CML, which lacked rearrangements within the major bcr (M bcr). With a series of genomic probes from this intronic region, we detected chromosomal breaks in all 22 patients within the 35 kb area, corresponding almost to the 3' half portion of the intron. The breakpoints were distributed throughout this region but we could not identify any special cluster of breakpoints in this area. Our data support consistent involvement of the 3' half part of the first BCR intron in Ph-positive leukaemias without M-bcr rearrangement, and indicate relatively wide scattering of breakpoints in this portion of the intron. PMID- 8435336 TI - Factors influencing haematological recovery in 53 patients with acute myeloid leukaemia in first remission after autologous bone marrow transplantation. AB - The kinetics of haematological recovery were retrospectively analysed in 53 patients with acute myeloid leukaemia in first remission after myeloablative chemoradiotherapy followed by autologous bone marrow transplantation. The median time to achieve a neutrophil count of 1 x 10(9)/l was 46 d (22-196 d) and median time to achieve unsupported platelet counts of 20 x 10(9)/l and 50 x 10(9)/l was 70 d (24-310 d) and 126 d (29-497 d) respectively. Multivariate analysis revealed two factors that were significantly associated with delayed neutrophil and platelet recovery: (1) use of high dose fractionated TBI and mononuclear cell cryopreservation, and (2) low platelet count at the time of bone marrow harvest. There was no correlation with: number of courses of chemotherapy, remission to ABMT interval, CMV status, indices of autograft quality or the development of elevated platelet associated immunoglobulin. Delayed haematological recovery did not predict for relapse or death. Delayed platelet recovery did, however, present significant problems with increased blood and platelet requirements and lengthening of hospital stay. PMID- 8435338 TI - Characterization of an acute micromegakaryocytic leukaemia: evidence for the pathogenesis of myelofibrosis. AB - The current hypothesis for the pathogenesis of myelofibrosis involves the intramedullary release of growth factors from defective or abnormal megakaryocytes. We describe a case of an acute micromegakaryocytic leukaemia, in a patient with chronic myelofibrosis, that provides additional evidence for this concept. The micromegakaryocytes, which reached 223 x 10(9)/l, were characterized morphologically by both light and electron microscopy, immunocytochemically and by platelet peroxidase activity. The cells were shown to have a mature cytoplasm, containing alpha granules and the associated proteins; vWF:Ag, fibrinogen, fibronectin and protein S. DNA analysis, by both a Seescan Solitaire Plus image analysis system and flow cytometry, revealed nuclear immaturity, with 92% of cells being diploid. Serum markers of connective tissue synthesis, namely carboxy terminal peptide of procollagen I (PICP), procollagen terminal peptide III (PIIIP) and laminin all increased significantly following transformation and were associated with an increase in platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta). These observations support the current hypothesis for bone marrow fibrosis formation and provide, for the first time, a link between in vivo growth factor release, bone marrow stromal turnover and megakaryocyte mass. In addition, the release of biologically active TGF-beta may explain both the increased fibronectin and angiogenesis characteristic of myelofibrotic bone marrow. PMID- 8435339 TI - The effects of leukaemia inhibitory factor on platelet function. AB - Leukaemia inhibitory factor (LIF) is able to promote megakaryocytopoiesis in vitro and elevate platelet counts in vivo, and is a potential new therapeutic agent for the treatment of thrombocytopenia. To determine whether platelets released under conditions of LIF-stimulated megakaryocytopoiesis have intact function, we compared aggregation responses of platelets from mice with constitutively elevated LIF levels (FD/LIF mice) and mice injected with recombinant murine LIF (rmLIF mice) with their respective control mice. We report that ex vivo platelet aggregability and thromboxane B2 release were intact in the LIF-treated mice, and were significantly enhanced in some situations. LIF-treated mice also had significantly increased platelet counts (FD/LIF mice: 1302 +/- 173 x 10(9)/l compared to 1012 +/- 99 x 10(9)/l for FD mice; rmLIF mice: 1460 +/- 193 x 10(9)/l compared to 985 +/- 67 x 10(9)/l for FCS/NS mice), increased platelet volumes and elevated plasma fibrinogen and calcium levels. The platelet hyperreactivity seen in the LIF-treated mice is likely to reflect the larger platelet volumes and/or the effect of plasma components such as fibrinogen, elevated levels of which were due to the concomitant action of LIF as a stimulant of acute phase protein synthesis. PMID- 8435340 TI - Type I von Willebrand disease, subtype 'platelet low': decreased platelet adhesion can be explained by low synthesis of von Willebrand factor in endothelial cells. AB - Endothelial cells (EC) were isolated from the umbilical vein of a newborn girl with type I 'platelet low' von Willebrand disease (I vWD) and endothelial localization and release and the ability of subendothelial von Willebrand factor (vWF) to support platelet adhesion were compared with those of normal EC. vWF was detectable by immunofluorescence in Weibel-Palade bodies, but the number of Weibel-Palade bodies positive for vWF was lower than in control EC. Patient EC released into the medium significantly smaller amount of vWF, both constitutively and after their stimulation. The vWF content of the extracellular matrix of patient EC was 38% that of control EC matrix. Platelet adhesion studies were performed under flow conditions with umbilical arteries and EC matrices of cultured EC. Using normal citrated whole blood as perfusate, platelet adhesion was lower in the umbilical artery of the patient (9 +/- 1% v 35 +/- 4% for the control) and in her EC matrix (7 +/- 1% v 21 +/- 2% of control). When patient EC matrix was perfused with vWF-deficient reconstituted blood, adhesion was 17 +/- 3% v 32 +/- 3% for control EC matrix; preincubation of patient EC matrix with 1 U/ml vWF increased the adhesion to 30 +/- 6%. These data establish that low contents of vWF in EC and subendothelium are important characteristics of type I vWD 'platelet low', and that such characteristics correlate with low platelet adhesion to the subendothelium. PMID- 8435341 TI - Substitution of cysteine for phenylalanine 751 in mature von Willebrand factor is a novel candidate mutation in a family with type IIA von Willebrand disease. AB - Type IIA is a variant form of von Willebrand disease (vWD) characterized by the absence of von Willebrand factor (vWF) high molecular weight multimers in plasma. Most of the candidate missense mutations potentially responsible for type IIA vWD have been found clustered within a short segment of vWF, lying between Gly742 and Glu875 of the mature subunit. The present work reports a single heterozygous T- >G transversion in eight patients from a large type IIA vWD family, resulting in the substitution Phe751-->Cys. The absence of this mutation in 100 normal vWF genes as well as the lack, in these patients, of any other abnormality within the whole exon 28 encoding amino acids 463-921 of mature vWF, provide a strong support that this non-conservative mutation may be at the origin of the disease in this family. The presence of an additional cysteine at position 751 may induce a conformational change of the vWF subunit affecting either its 'in vivo' sensitivity to proteolytic cleavage or, more likely, its intracellular transport as suggested by the abnormal multimeric pattern of platelet vWF observed in these patients. PMID- 8435342 TI - An assessment of exposure to glutaraldehyde in hospitals: typical exposure levels and recommended control measures. AB - An assessment of exposure to glutaraldehyde in cold sterilisation and x ray development processes was undertaken in 14 locations at six hospitals in south east England. The results obtained indicate that routine exposures of hospital workers to airborne concentrations of the compound are within the current United Kingdom occupational exposure limit of 0.7 mg m-3. There was the potential for skin contact in many of the activities observed and alternative sterilisation and disinfection procedures would have been more appropriate in some situations. Recommendations are made on reducing exposures as the current occupational exposure limit for this compound may not be appropriate. PMID- 8435343 TI - Comprehensive health evaluation of workers in the ceramics industry. AB - A cross sectional study on ceramics workers in the Seto area of Japan was conducted to determine whether there are differences in the morbidity pattern and overall health among the working populations employed by different sized companies engaged in the ceramics industry. The study population consisted of 3324 male ceramics workers (age range 40-69) who participated in the Seto occupational health screening programme in 1990. The prevalences of pulmonary diseases (silicosis and tuberculosis) and findings of some nonpulmonary diseases were compared in terms of company size by categories of 1-19, 20-49, 50-99, and 100 or more employees. The values of various screening tests were subjected to principle component analysis to extract factors representing key indices of health state. The average factor scores stratified by company size were used to quantitatively evaluate the comprehensive health level. Both prevalence and multivariate analysis showed that the employees working for smaller companies had overall worse health. The smaller the company, the higher the prevalence and the lower the health scores for silicosis and pulmonary tuberculosis tended to be; significantly increased rates and lower health scores for hypertension, anaemia, and glucosuria among small companies were also found when compared with larger companies. The high morbidity of silicosis and pulmonary tuberculosis in smaller companies contributed most to the decline in the overall health level. PMID- 8435344 TI - Mortality from stomach cancer in Ontario miners. AB - An excess of mortality from stomach cancer has been found in Ontario gold miners (observed (obs) 104, standardised mortality ratio (SMR) 152, 95% confidence interval (95% CI) 125-185) and no excess of stomach cancer could be detected in other miners in Ontario (obs 74, SMR 102, 95% CI 80-128). The excess of stomach cancer appeared five to 19 years after the miners began gold mining in Ontario. In that interval, similar patterns of excess mortality from stomach cancer were found in miners born in north America (obs 14, SMR 268, CI 147-450) and in miners born outside north America (obs 12, SMR 280, 95% CI 145-489). Twenty or more years after the miners began mining gold, an excess of mortality from stomach cancer was found in gold miners born outside of north American (obs 41, SMR 160, 95% CI 115-218) but not in gold miners born in north America (obs 37, SMR 113, 95% CI 80-156). The excess of stomach cancer in gold miners under the age of 60 (obs 45, SMR 167, 95% CI 122-223) seems larger than the excess in gold miners between the ages of 60 and 74 (obs 59, SMR 143, 95% CI 109-184). Exposures to arsenic, chromium, mineral fibre, diesel emissions, and aluminium powder were considered as possible explanations of the excess of stomach cancer in Ontario gold miners. Exposure to diesel emissions and aluminium powder was rejected as gold miners and uranium miners were exposed to both agents but an excess of stomach cancer was noted only in gold miners. The association between the excess of stomach cancer and the time since the miner began mining gold suggested that duration of exposure to dust in gold mines ought to be weighted according to the time since the exposure to dust occurred and that an appropriate time weighting function would be one in the interval five to 19 years after each year of exposure to dust and zero otherwise. A statistically significant association between the relative risk of mortality from stomach cancer and the time weighted duration of exposure to dust in gold mines was found in miners under the age of 60. Time weighted indices of exposure to chromium and arsenic were formed for each gold miner by time weighting the product of the duration of exposure to dust in a gold mine and the percentages of arsenic and chromium in rocks in that gold mine. Exposure to mineral fibre was measured in terms of the time weighted duration of employment in those gold mines that contain mineral fibre. A statistically significant association between the excess of stomach cancer in gold miners under the age of 60 and the time weighted index of exposure to chromium occurred and not association was found between the excess of stomach cancer and either the time weighted duration of employment in mines containing mineral fibre. The excess of stomach cancer in gold miners under the age of 60 was better associated with the time weighted index of exposure to chromium than to the time weighted duration of exposure to dust in gold mines. Although the number of cases of gastric cancer that were classified according to the system of Lauren was small, the data suggest that for miners under the age of 60, exposure to chromium is associated with the development of the intestinal rather than the diffuse type of gastric cancer. PMID- 8435345 TI - Mortality in retired coke oven plant workers. AB - A previous study on 536 retired coke oven plant workers in Lorraine Collieries (France) reported an excess of deaths from lung cancer (standardised mortality ratio (SMR) = 251) compared with the French male population. Occupational exposures during working life were retraced for each subject, but the number of deaths during the observation period (1963-82) was small, and smoking habits were known only for dead subjects. In 1988, the cohort was re-examined (182 deaths occurred between 1963 and 1987) and smoking habits were determined for all the subjects. This study confirmed the excess of lung cancer (SMR = 238, p < 0.001). It showed an excess of mortality from all causes (SMR = 141, p < 0.001), overall cancers (SMR = 133, p < 0.05), and cardiovascular diseases (SMR = 133, p < 0.05). A significant excess of deaths was found for subjects who worked near the ovens for all causes (145, p < 0.01), lung cancer (SMR = 252, p < 0.01), colon cancer (SMR = 381, p < 0.05), and cardiovascular diseases (SMR = 155, p < 0.05). A significant excess mortality was also found from all causes (176, p < 0.05) and stomach cancer (SMR = 538, p < 0.01) in subjects who worked in byproducts, from lung cancer (SMR = 433, p < 0.001) in those in the workshops, and from cirrhosis of the liver and alcoholism (SMR = 360, p < 0.01) in those underground; but, due to small numbers, these figures were not robust. An excess of mortality from all causes (SMR = 163, p<001), lung cancer (SMR = 228, p<0.05) and cardiovascular diseases (SMR = 179, p<0.01) was shown also for non-exposed or slightly exposed subjects. The fact that, on the whole, mortality of various exposed groups was similar to that of non-exposed or slightly exposed workers may be explained in part by the selection at hiring and the healthy worker effect. As an increased risk of lung cancer was noted among subjects who worked in the old generations of plant compared with the other workers (although the relative risk was not significant) it is concluded that the role of occupational hazards could not be excluded. PMID- 8435346 TI - Chemical exposures and respiratory cancer among Finnish woodworkers. AB - A case-control study of respiratory cancer, nested within a cohort of male woodworkers, was updated in Finland. The update extended the initial follow up of 3805 workers from 19 plants to 7307 workers from 35 plants. Each case of respiratory cancer (n = 136) diagnosed between 1957 and 1982 within the cohort was matched by year of birth with three controls (n = 408) from the cohort. Chemical exposures were assessed for the cases and the controls by a plant and period specific job exposure matrix. An excess of respiratory cancer was associated with phenol. Concomitant exposures to several other agents occurred as well, however, and no exposure-response relation for phenol was seen. An excess risk and an increasing exposure-response relation were found for engine exhaust from petrol and diesel driven factory trucks. The excess risk associated with pesticides was lower than in our previous study, an indication of qualitative and quantitative differences in exposure between the initial and augmented cohorts. Slightly increased risks were found for terpenes and mould spores, which may be due to chance although the contribution of occupational exposure cannot be ruled out. Exposure to wood dust, mainly from pine, spruce and birch, at a level of about 1 mg/m3, was not associated with lung cancer, upper respiratory cancer, or adenocarcinoma of the lung. PMID- 8435347 TI - Sister chromatid exchanges in lymphocytes of petroleum retailers. AB - Occupational exposure to petroleum vapour was assessed in workers employed in suburban petroleum retail outlets. Urinary output of thioethers provided a non specific estimate of exposure to chemicals metabolised via a mercapturic acid pathway. Urinary d-glucaric acid (DGA) excretion was taken as an estimate of hepatic enzyme activity. Sister chromatid exchange frequency in lymphocytes was used as an indicator of genotoxic response to exposure. Workers were classified according to their employment at self service (where customers operate petrol pumps) or at driveway attended service stations (at which an employee operates the pumps), and according to exposure to cigarette smoke on the basis of urinary cotinine excretion. Prework and postwork urine samples of workers employed at driveway attended petrol stations contained more thioether than did those of self serve workers. When classified according to smoking behaviour there were no statistically significant differences, although thioether excretion tended to be higher in smokers than in nonsmokers. Urinary DGA excretion was similar in the two exposure groups. Cigarette smokers excreted more DGA, however, than nonsmokers. Sister chromatid exchange frequencies were higher in driveway attendants than in self serve personnel. When the influence of cigarette smoking was investigated there was a significant increase of sister chromatid exchange with combined exposure to petrol and cigarette smoking, but not with either factor alone. Correlation analysis showed that urinary cotinine concentrations were positively associated with urinary excretion of thioether and DGA, indicating that cigarette smoke induces the activity of hepatic enzymes and acts as a source of substrates metabolised through a thioether pathway. In conclusion it seems that exposure to petroleum vapour causes increased sister chromatid exchange in circulating lymphocytes of cigarette smokers, possibly as a result of enhanced hepatic conversion of vapour components to reactive metabolites. Urinary thioether output does not clearly discriminate between workers exposed to different amounts of petroleum vapour at retail outlets. PMID- 8435348 TI - Systemic effects of inhalational methyl bromide poisoning: a study of nine cases occupationally exposed due to inadvertent spread during fumigation. AB - Systemic methyl bromide (CH3Br) poisoning with signs and symptoms of varying severity developed in nine greenhouse workers after acute inhalational exposure on two consecutive days. Measurements of CH3Br, carried out at the site within hours after the accident, suggest that exposure on the second day may have been in excess of 200 ppm (800 mg/m3) CH3Br. All workers were admitted for observation. Seven of them were discharged after an uneventful overnight observation and residual symptoms, if any, subsided within three weeks of the accident. Two patients needed intensive care for several weeks because of severe reactive myoclonus and tonic-clonic generalised convulsions. These conditions were unresponsive to repeated doses of diazepam, clonazepam, and diphenylhydantoin but could be suppressed effectively by induction of a thiopental coma that had to be continued for three weeks. In some of the patients prior subchronic exposure to CH3Br, as shown by their occupational histories and high serum bromide (Br-) concentrations, is likely to have been a factor contributing to the severity of their symptoms. A direct association between serum Br- concentrations and the severity of neurological symptoms, however, seemed to be absent. An on site investigation into the circumstances leading to the accident showed the presence of an empty and out of use drainage system that covered both sections of the greenhouse. This was probably the most important factor contributing to the rapid and inadvertent spread of CH3Br. PMID- 8435349 TI - An investigation into the acute vascular effects of riveting. AB - Measurements were made on 46 pairs of riveters and matched control subjects before and after a morning's work. Before starting work, the mean resting finger systolic pressure was 112 (SEM 3.3) mm Hg in the riveters, similar to 117 (1.7) in the control subjects. After cooling the middle phalanx to 10 degrees C for five minutes, 16 riveters but only one control subject exhibited digital vasospasm and these numbers were unaltered after a morning's work. A subgroup of riveters whose role was always to provide counter pressure to the rivet gun showed a higher incidence (45%) of cold induced vasospasm than did riveters who invariably held the gun (10%) or rotated between both roles (27%). Plasma levels of three markers of vascular activity, endothelin-1 (ET-1), von Willebrand factor antigen (vWFAg), and angiotensin converting enzyme (ACE), were measured in non smoking riveters and control subjects. Before work, ET-1 concentrations were slightly lower (p < 0.05) in the riveters, but vWFAg concentration and ACE activity were similar in riveters and control subjects. Riveting for a morning did not alter ET-1 concentration or ACE activity but did induce a small increase (p < 0.05) in vWFAg concentration, which may indicate damage to the endothelium. This type of vascular assessment may be helpful in assessing vasospastic complications in workers exposed to vibration. PMID- 8435350 TI - Long term effects of alumina on components of bronchoalveolar lavage fluid from rats. AB - Significant differences in several components of bronchoalveolar lavage fluid (BAL fluid) have previously been reported in aluminium potroom workers compared with controls. The present paper describes the long term effects in rats of one time exposure to potroom aluminium oxide without fluorides (primary alumina (PA)) or with adsorbed fluorides (secondary alumina (SA)) on components of BAL fluid. Alumina dust (40 mg) suspended in saline was instilled intratracheally; controls received saline. Bronchoalveolar lavage (BAL) was performed one, four, and 12 months after exposure. The number of cells in BAL fluid was increased significantly (p < 0.05) by SA but not PA. The increase was mainly macrophages, but the concentrations of neutrophils also increased about 10-fold one and 12 months after exposure. Although albumin and hyaluronan concentrations did not differ from those of controls, fibronectin concentrations were significantly (p < 0.001) increased one year after exposure both in PA exposed and SA exposed rats. The results indicate that SA, possibly because of adhered fluorides, induces early changes in alveolar cell populations including persistent neutrophilia. These cellular changes may have a destructive effect. The late pronounced increase of fibronectin in both PA and SA exposed rats indicates a delayed effect of alumina on the extracellular matrix. PMID- 8435351 TI - Distribution of radioactivity from 14C-formaldehyde in pregnant mice and their fetuses. AB - The distribution of 14C after the administration of 14C-formaldehyde was studied in pregnant mice by a whole body low temperature autoradiographic technique. The concentrations of formaldehyde and its metabolites in maternal and fetal blood and tissues were determined in unsectioned tissues by liquid scintillation spectrophotometry. The binding of 14C from 14C-formaldehyde to cells and DNA in maternal and fetal mouse liver was also measured. Radioactivity of 14C deriving from 14C-formaldehyde was found immediately after injection, and showed strong accumulation and retention three hours after injection. The organs that had high concentrations at all studied survival intervals were maternal liver, intestinal mucosa, bone marrow, kidneys, and salivary glands. Considerable amounts of radioactivity were found in the fetuses at six hours after injection, and the concentrations were almost the same as in the maternal tissues. The elimination of 14C-formaldehyde and metabolites from the placenta and fetus occurred more slowly than from maternal tissue. PMID- 8435352 TI - The immune system as target for subclinical lead related toxicity. PMID- 8435353 TI - Haemolytic anaemia in a case of occupational asthma due to maleic anhydride. PMID- 8435354 TI - Chronic mercury poisoning. 1946. PMID- 8435355 TI - Reversal of multidrug resistance in breast cancer: many more open questions than answers. PMID- 8435357 TI - A new group on AIDS and tumors approved by the EORTC board. PMID- 8435356 TI - Management of bowel obstruction in advanced and terminal cancer patients. AB - BACKGROUND: Bowel obstruction is a common and distressing outcome in patients with abdominal or pelvic cancer. PATIENTS AND METHOD: Patients may develop bowel obstruction at any time in their clinical history, with an incidence ranging from 5.5% to 42% in ovarian carcinoma and from 10% to 28.4% in colorectal cancer. The causes of the obstruction may be benign postoperative adhesions, a focal malignant or benign deposit, relapse or diffuse carcinomatosis. The symptoms which are almost always present are intestinal colic (reported in 72%-76% of patients), abdominal pain due to distension, hepatomegaly or tumor masses (in 92% of patients) and vomiting (68%-100%) of cases. CONCLUSION: While surgery must remain the primary treatment for malignant obstruction, it is now recognised that there is a group of patients with advanced disease or poor general condition who are unfit for surgery and require alternative management to relieve distressing symptoms. A number of treatment options are now available for the patient with advanced cancer who develops intestinal obstruction. In this review of the literature, the indications for surgery will be examined, the use of nasogastric tube and percutaneous gastrostomy evaluated and the place of drugs for symptom control described. PMID- 8435358 TI - Escalating drug delivery in cancer chemotherapy: a review of concepts and practice--Part 1. PMID- 8435359 TI - Nobel's day on recent advances in cancer research. AB - The June 7-10th Symposium on 'Recent Advances in Cancer Research', organized by Lorenzo Moretta in San Remo, Italy, on the occasion of Nobel's day, designated cancer genetics and tumor immunology as forefront areas in fundamental cancer research. While the central importance of oncogenes is obvious, this is less the case for the immunology of tumors, which has long been an area of descriptive phenomenology, wild speculation and unfulfilled expectation. The recent molecular identification of genes encoding a human melanoma antigen recognized by T cells, and of cytokines involved in the tumor-host interaction justifies renewed oncological interest in this area. PMID- 8435360 TI - Pediatric oncology in developing countries: a cooperative program in Nicaragua. PMID- 8435361 TI - The impact of mammography on breast cancer detection. AB - BACKGROUND: Mammography has different effects on the epidemiology of breast cancer, i.e., while increasing the registered incidence it can reduce mortality. This study was aimed at obtaining quantitative estimates of the impact of mammography on breast cancer detection. SUBJECTS AND METHODS: A case-control study was conducted in Northern Italy between 1985 and 1991 on 2596 cases of histologically confirmed breast cancer and 2005 controls in hospital for acute diseases unrelated to known or suspected risk factors for breast cancer. RESULTS: 15.6% of the patients reported one screening mammography and 9.7% two or more. The age-adjusted breast cancer diagnosis odds ratios (OR) were 1.3 (95% confidence interval, CI 1.1 to 1.5) for one mammography and 2.0 (95% CI 1.6 to 2.6) for two or more. When allowance was made for major identified potential distorting factors, the OR decreased to 1.0 (95% CI 0.8 to 1.2) for one, and 1.3 (95% CI 1.0 to 1.8) for two or more mammographies. In the age-adjusted analysis, the association between screening mammography and breast cancer detection was apparently stronger for younger and pre-menopausal women, among more educated women and those with no history of benign breast disease or breast biopsy, and among women who had first-degree relatives with histories of breast cancer. CONCLUSIONS: Although the association between mammography and breast cancer was largely explained by selective screening, confirming at the epidemiological level that the relationship is incidental, the unadjusted ratios are of public health interest, since they give a measure of the role of mammography in breast cancer detection. PMID- 8435362 TI - Randomized phase II study of single-agent epirubicin +/- verapamil in patients with advanced metastatic breast cancer. An AIO clinical trial. Arbeitsgemeinschaft Internistische Onkologie of the German Cancer Society. AB - BACKGROUND: Anthracyclines are the most active cytostatic agents in patients with metastatic breast cancer. Drug resistance and dose intensity are relevant issues in the treatment of cancer. METHODS: A randomized phase II study in 51 patients with advanced progressive metastatic breast cancer was performed. Twenty-six were treated with epirubicin (EPI) 120 mg/m2 i.v. bolus injection divided over three days combined with a daily dose of 480 mg verapamil (VPL) orally administered one day before and during EPI. Twenty-five patients received the same dose and schedule of EPI without VPL. Evaluation of response was carried out after three 21-day cycles. Study endpoints were objective response rate and overall survival. RESULTS: Among the 24 evaluable patients treated with EPI+VPL 1 CR (4%), 7 PR (29%), 9 NC (38%) and 7 PD (29%) were observed. Two patients were excluded because of toxicity. Among the 24 evaluable patients treated with EPI alone 8 PR (28%), 6 NC (24%) and 10 PD (40%) were observed, and one patient was excluded because of toxicity. Myelotoxicity was the major side effect followed by alopecia, stomatitis/mucositis and nausea. The patient group treated with VPL had lower blood pressure levels during therapy, with complete normalization after discontinuation of VPL. The median overall survival times were similar: 7.4 month in the EPI group and 8.9 month in the EPI+VPL group. CONCLUSION: In both treatment groups the objective response rate was about 30% and the overall survival rates were also the same. No clinical relevance could be demonstrated for the hypothesized resistance modifying action of VPL. Furthermore, VPL did not increase the toxicity of EPI. PMID- 8435363 TI - The clinical relevance of t(14;18)/BCL-2 rearrangement and DEL 6q in diffuse large cell lymphoma and immunoblastic lymphoma. AB - BACKGROUND: t(14;18)/bcl-2 gene rearrangement (R) is claimed to impart a worse rate of complete remission and disease-free survival in diffuse large cell lymphoma (DLCL). DEL 6q has also been associated with poor outcome. DESIGN: Retrospective study of 54 patients with either diffuse large cell or immunoblastic lymphoma who had cytogenetics and/or molecular studies performed. RESULTS: Patient characteristics, complete remission rate, and time to treatment failure (TTF) were similar at three year follow-up for groups with and without t(14;18)/BCL-2R. Survival was worse for the former but the difference was not statistically significant. For DEL 6q, patient characteristics and survival rates were similar at three year follow-up for patients with and without the abnormality. TTF was worse for the former but this was not statistically significant. CONCLUSION: This study, with equal or greater number of patients with t(14;18) than previous reports, fails to show a worse prognosis for patients with the t(14;18) chromosomal abnormality. A definite association will await further accrual of patients and a meaningful multivariate analysis. PMID- 8435364 TI - High-dose cisplatin and cyclophosphamide with glutathione in the treatment of advanced ovarian cancer. AB - BACKGROUND: On the basis of preliminary results achieved with a high-dose cisplatin regimen including glutathione as chemoprotector, the efficacy and toxicity of the new regimen was further evaluated in a larger series of patients with advanced ovarian cancer (stage III and IV). PATIENTS AND METHODS: The study included patients with bulky or extensive residual disease after primary laparotomy or with bulky inoperable tumor masses. A total of 79 patients were treated with up to five courses of high-dose cisplatin (40 mg/m2 daily in normal saline, for four days) plus glutathione (2500 mg as a short-term infusion before cisplatin), together with cyclophosphamide (600 mg/m2 as an i.v. bolus on day 4). A standard i.v. hydration consisting of a total of 2000 ml of fluids without diuretics was employed. RESULTS: All eligible patients, who received a total of 345 courses, were assessed for response and toxicity and 52 received the planned five courses of the protocol. Forty-five patients (57%) achieved complete clinical responses and 20 (25%) had partial remissions for an overall response rate of 82%. The response rate was critically dependent on tumor size before chemotherapy. Thirty-eight of 45 patients who had complete clinical responses underwent second-look laparotomy, and 29 had pathological complete responses (37%). Seventeen of these 29 patients subsequently relapsed (median disease-free interval, 12 months; range, 6-45). With a median follow-up time of 44 months, the median survival for the 79 analyzed cases was 40 months. The toxicity of the regimen was moderate. Nausea/vomiting was the most severe acute toxicity. Myelotoxicity was acceptable, with severe leukopenia and thrombocytopenia (grade 4) occurring in 8% and 3% of patients, respectively. Nephrotoxicity was minimal with a transient increase (to < 2 mg/dL) in serum creatinine in only 6 patients (8%). Peripheral neurotoxicity and ototoxicity were the most significant long term toxicities. The severity of these side effects (grade 3 WHO neurotoxicity occurred in only 4% of patients) was apparently less than has been reported with other high-dose cisplatin regimens. Neurotoxicity required discontinuation of therapy in three patients after four courses. Most affected patients had complete or partial recovery of symptoms with time. DISCUSSION: The efficacy and tolerability of the regimen confirm the feasibility of this new approach including glutathione in order to increase cisplatin dose intensity. The superiority of this regimen over standard induction therapy should be confirmed in randomized trials. PMID- 8435365 TI - E-SHAP: inadequate treatment for poor-prognosis recurrent lymphoma. AB - BACKGROUND: The treatment of refractory and recurrent lymphomas remains problematic, with the majority of patients showing no response to 'salvage' therapies. One regimen which has been suggested as showing particular efficacy is etoposide (40 mg/m2 daily x 4), cytosine arabinoside (2.0 g/m2 one dose), cisplatin (25 mg/m2/day infused over 4 days) and methylprednisolone (500 mg daily x 4) (E-SHAP). This study attempted to reproduce the encouraging results seen with this regimen in North America. PATIENTS AND METHODS: Twenty-eight patients with recurrent or refractory lymphoma were treated with E-SHAP given 3 to 4 weekly. Thirteen patients were treated at first recurrence and twenty-two had previously received etoposide. RESULTS: No objective responses were seen although five patients had a transient reduction in tumour before regrowth despite continued treatment. Sixteen patients received further chemotherapy after failure of E-SHAP of whom four had responses. The principal toxicity was myelosuppression with over half the patients requiring hospital admission for neutropenia associated fever. Median time to treatment failure was 2.5 months and median survival 7 months from the start of E-SHAP. CONCLUSIONS: These results are in marked contrast to those reported from North America, possibly due to differing patient selection. E-SHAP shows strictly limited efficacy but marked toxicity in the treatment of recurrent or refractory lymphomas with poor prognostic features. PMID- 8435367 TI - North-south asymmetry. PMID- 8435366 TI - Psychosocial problems in head-and-neck cancer patients and their change with time since diagnosis. AB - BACKGROUND: Little is known about the psychosocial effects of cancer survivors especially after the first stage of adjustment. The study was designed to provide information about the major psychological problems of head-and-neck cancer patients and their change with time since diagnosis. PATIENTS AND METHODS: The subjects were 55 head-and-neck cancer patients, 40 men and 15 women with disease stages I to IV, grade of tumors G1 to G3-4, and disease duration in the range of 3 months to 21 years. A questionnaire with multiple-choice and open-ended questions assessing adjustment in 14 domains (e.g., fears and worries concerning health, functioning in the family) was administered to patients and their partners or closest relatives as well as scales assessing anxiety, anger and depression. RESULTS: The results showed that the domains that were most problem laden included coping with health problems, fears, communication with the partner and social relations. Comparing the problems of patients in different time periods (0.5-1.5 years after diagnosis, 1.5-5 years, and over 5 years) showed that many medical problems decreased with time but most psychological ones including anxiety and anger deteriorated markedly. CONCLUSIONS: Head-and-neck cancer patients suffer from a broad range of psychosocial problems that become exacerbated with time. The deterioration in quality of life may reflect 'patient burnout' which could be decreased by acquiring adequate coping skills. PMID- 8435368 TI - DNA aneuploidy and cell proliferation in relation to histology and prognosis in patients with Hodgkin's disease. AB - BACKGROUND: Aneuploidy and S-phase fraction are well recognized prognostic features of solid tumors and non-Hodgkin's lymphoma. However, only limited data on Hodgkin's disease are available. PATIENTS AND METHODS: In this study flow cytometric data on ploidy status and S-phase fraction are analyzed in relation to clinical characteristics and prognosis in 137 patients with Hodgkin's disease. RESULTS: The presence of DNA aneuploidy was not associated with other clinical characteristics. When the histologic subtypes were clustered according to a higher number of Reed-Sternberg/Hodgkin cells into two classes (LP + NSI and the histologic NSII + MC + LD), it appeared that cases with an SPF > or = 7.5% had the histologic subtypes NSII + MC + LD significantly more frequently than those with an SPF < 7.5% (P = 0.001). There was no significant difference in complete remission rates, relapse-free or overall survivals between the patients with diploid and those with aneuploid lymph nodes. The complete remission rate for patients with and SPF < 7.5% was higher than for those with an SPF > or = 7.5%, 95% (56/59) and 76% (50/66), respectively (P = 0.006). The 10-year survival rate was 78% for patients with an SPF < 7.5% and 48% for those with an SPF > or = 7.5% (P = 0.04). However, by multivariate analysis only the ESR, age and clinical stage proved to be of independent prognostic importance. CONCLUSION: DNA aneuploidy did not correlate with known prognostic factors or survival, but the SPF might turn out to be an indicator of patients who will have less favourable outcomes. PMID- 8435369 TI - Combination chemotherapy with tauromustine (TCNU), 5-fluorouracil and leucovorin in advanced colorectal carcinoma: a dose-finding study. AB - BACKGROUND: In preparation for a phase II trial we performed a dose-finding study involving tauromustine (TCNU), fluorouracil (5-FU) and leucovorin (LV), applied in patients with colon cancer. To prevent TCNU/5-FU antagonism, a phenomenon recently demonstrated in vitro, special attention was paid to the sequencing of these agents. PATIENTS AND METHODS: In 25 patients with advanced colorectal carcinoma (13 M, 12 F, median age 51 yrs), four dose levels of TCNU (25, 30, 35 or 40 mg/m2) were investigated. The agent was administered orally once per week in weeks 1 through 4, in combination with fixed i.v. doses of 400 mg/m2 5-FU and 80 mg/m2 LV, once a week, weeks 1 through 8. Unless progression occurred, two 8 week cycles were applied. TCNU was administered at least 24 hours prior to 5-FU, because recent in vitro studies suggested that such an interval is required to obtain additive cytotoxicity. RESULTS: All 25 patients were evaluable for toxicity; 23 patients received at least one full 8-week course, and 13 were eligible for second cycles. Significant haematologic toxicity, predominantly thrombocytopenia WHO grade 3 or 4, was mainly encountered at the 35 and 40 mg/m2 dose levels. Although occasionally severe, myelosuppression did not result in toxic deaths; spontaneous haemorrhage was never observed, and platelet transfusions were not required. Additional toxicity, also related to the two higher dose levels, consisted of diarrhea (WHO grade 3) and the 'hand and foot syndrome', both occurring in a single patient; two patients developed fever of undetermined origin, but only one of them required hospitalization and antibiotic treatment. The overall response rate was 20% (7 partial responses in 25 evaluable patients). CONCLUSIONS: For phase II studies, we recommend a weekly oral dose of 40 mg/m2 TCNU, weeks 1 through 4, in combination with 400 mg/m2 5-FU and 80 mg/m2 LV (IV), once a week, weeks 1 through 8. PMID- 8435370 TI - 5-Fluorouracil, leucovorin and interferon alpha 2b in advanced pancreatic cancer: a pilot study. AB - BACKGROUND: On the basis of data suggesting the possibility of maximizing the efficacy of 5-FU by LV and IFN, a pilot clinical trial was initiated in advanced pancreatic cancer. PATIENTS AND METHODS: Twenty-four patients received weekly 5 FU 600 mg/m2 bolus 1 hour after the initiation of a 2-hour infusion of 500 mg/m2 of leucovorin. Three MU of interferon alpha 2b was administered subcutaneously three times a week. RESULTS: Two of 22 evaluable patients obtained partial responses (8%, confidence interval 3%-33%). Toxicity was severe. Diarrhea and stomatitis were the most common side effects, occurring in 50% and 25% of patients, respectively. CONCLUSION: Because of the presence of severe toxicity we suggest that further clinical trials in pancreatic cancer be attempted only after a better definition in preclinical studies of interactions among 5-FU, leucovorin and interferon. PMID- 8435371 TI - Lung cancer in 19 patients with HIV infection. The Italian Cooperative Study Group on AIDS and Tumors (GICAT) PMID- 8435372 TI - Mammography and overdiagnosis. PMID- 8435373 TI - Renal and extrarenal sites of action of diuretics. AB - This paper provides (a) a survey of the basic tubule transport mechanisms of sodium and potassium ions along the nephron, (b) a comparison of the overall renal effects of two diuretic agents (torasemide and furosemide), as assessed by renal clearance techniques, (c) an analysis of the tubule sites of action of torasemide evaluated by free-flow micropuncture and microperfusion techniques, and (d) a brief evaluation of some extrarenal transport effects of loop diuretics. PMID- 8435374 TI - Clinicopharmacological reappraisal of the potency of diuretics. AB - From a clinicopharmacological standpoint, the urinary excretory potency of diuretics should be assessed comparatively on the basis of the changes in 24-hour natriuresis, with respect to 24-hour natriuresis after placebo, caused by single oral doses administered to healthy adult subjects who are in habitual and steady state external sodium balance. The potency of various formulations of loop (e.g., furosemide), of early distal tubular (e.g., the thiazides), and of potassium retaining diuretics, as well as of several combinations of diuretics, has been evaluated in a series of studies. Two formulations of loop diuretics (muzolimine 20 mg and torasemide 2.5 mg) are definitely nondiuretic. The majority of the other formulations of loop diuretics studied are, in general, comparatively less potent than most of the common formulations of early distal tubular diuretics studied. As a general rule, most common formulations of early distal tubular diuretics are at least not less potent than the majority of common formulations of loop diuretics. Hydrochlorothiazide 25 mg and furosemide 80 mg have similar potencies. Loop diuretics increase mean renal sodium output strikingly within the first few (0-6) hours after dosing, but this forced excretion is followed by a rebound with respect to postplacebo mean urinary sodium flow; the rebound usually takes place between 6 and 24 hours after dosing. However, no rebound in mean urinary sodium flow occurs during the 24 hours following a single dose of a distal tubular diuretic; these substances increase urinary sodium excretion with lower maximal intensity but more protractedly than loop diuretics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8435375 TI - Renal excretory responses to single and repeated administration of diuretics in healthy subjects: clinical connotations. AB - Administration of an initial oral dose of hydrochlorothiazide 25 mg to healthy subjects is followed by increased 24-hour urinary outputs of sodium, chloride, and potassium. On the fourth day of once-daily dosing with hydrochlorothiazide 25 mg, 24-hour natriuresis and chloriuresis are no longer augmented, but the elevation in 24-hour kaliuresis that follows the first dose remains unchanged. Twenty-four-hour urinary calcium output is consistently reduced during repeated once-daily administration of hydrochlorothiazide 25 mg. The first oral dose of the loop diuretic torasemide augments the average natriuresis and kaliuresis in the 6 hours immediately after dosing in healthy subjects, in a dose-dependent fashion, within the 2.5 to 10-mg range. These increased urinary outputs are followed by rebounds below postplacebo values between 6 and 24 hours after dosing. As a result of this biphasic response, torasemide 2.5 mg qualifies as a nondiuretic formulation (it does not elevate 24-hour natriuresis), whereas torasemide 5 and 10 mg qualify as diuretic formulations. After the seventh dose of torasemide 5 or 10 mg during a regimen of once-daily therapy, 24-hour urinary sodium and chloride outputs no longer differ from their postplacebo counterparts. Twenty-four-hour kaliuresis tends to increase in a dose-dependent fashion after the first dose of torasemide (torasemide 2.5 and 5 mg do not augment it significantly), but this tendency is no longer present after the seventh once daily dose, when torasemide (2.5, 5, or 10 mg) does not elevate the mean 24-hour kaliuresis. Twenty-four-hour calciuresis tends to increase in a dose-dependent manner (torasemide 2.5 mg does not elevate it significantly) after the first dose of torasemide; this calciuretic effect does not change in intensity after 7 days of once-daily treatment. The time course of natriuresis over the 24 hours following the administration of any given formulation of a loop or of an early distal tubular diuretic to healthy subjects is alike after the first and after the nth once-daily dose; therefore, it constitutes a definite characteristic of any given oral formulation. In the case of torasemide, lower doses have more protracted effects on natriuresis, to the extent that the time course of natriuresis over the 24 hours after administration of torasemide 2.5 mg to healthy subjects resembles the time course after administration of hydrochlorothiazide 25 mg, rather than the time course after administration of the overtly diuretic formulation torasemide 10 mg. PMID- 8435376 TI - Central hemodynamic effects of diuretic therapy in chronic heart failure. AB - In chronic heart failure diuretic drugs improve central hemodynamic variables and cardiac pumping secondary to altered plasma and extracellular volumes; humoral markers of these changes include increased plasma renin and aldosterone levels. The latter increases are maximal over the first week but decline with chronic therapy. The plasma alpha-ANP levels show a reciprocal effect; these data are compatible with a rapid contraction of the plasma volume which is sustained during chronic therapy. The acute hemodynamic actions of diuretic agents reflect both immediate and direct vascular actions and also effects secondary to diuresis (volume redistribution). At rest substantial reductions in pulmonary "wedge" pressure (-29%), with a consequent fall in cardiac output (-10%), are described. Total systemic vascular resistance initially increases but "reverse autoregulation" over subsequent weeks returns this elevation gradually towards control values. Tolerance to these initial hemodynamic effects does not occur with maintained therapy; moreover, echocardiographic markers of contractility and exercise capacity may increase. The early venodilator effects of diuretic drugs can be attributed to prostaglandin release and the initial pressor actions to activation of the renin angiotensin system; these vascular actions may have limited relevance to long-term beneficial effects on hemodynamics. Direct pulmonary vasodilation and improved pulmonary compliance remain an interesting finding. Although most patients are both symptomatically and hemodynamically improved at rest, the actions during exercise are more varied. Some individuals with severely impaired left ventricular function show little hemodynamic improvement, whereas those with milder dysfunction usually benefit; in the main this is probably related to the latter being on a steeper cardiac function curve.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8435378 TI - Torasemide in comparison with thiazides in the treatment of hypertension. AB - There are a number of clinically relevant differences between torasemide and the thiazide diuretics in the treatment of hypertension. Only 2.5-5 mg torasemide once daily is sufficient for antihypertensive treatment; these low doses of torasemide exert comparable antihypertensive effects to those of the overtly natriuretic doses of thiazides (e.g., hydrochlorothiazide 25 mg) that are currently used once daily for the treatment of hypertension. Whereas natriuretic thiazide doses reduce blood pressure rapidly, the blood pressure-lowering effect of low-dose torasemide appears to occur more gradually during the first weeks of treatment. The diurnal blood pressure rhythm is not altered by either drug. In contrast to the thiazides, torasemide does not cause significant renal potassium loss in doses recommended to treat hypertension. Long-term antihypertensive treatment with torasemide has not resulted in undesired metabolic side effects, such as hypomagnesemia, alterations in glucose and lipid metabolism, or hyperuricemia. As compared with the thiazides, torasemide appears to be a safer and equally effective alternative for antihypertensive treatment when subdiuretic doses of this loop diuretic are used. PMID- 8435377 TI - The place of diuretics in the treatment of hypertension: a historical review of classical experience over 30 years. AB - Thiazide diuretics have been the mainstay of antihypertensive therapy for over 30 years. Their precise mechanism of antihypertensive action is still incompletely understood. They reduce arterial pressure initially through a fall in plasma volume and cardiac output. However, with chronic administration cardiac output tends to return toward pretreatment levels, suggesting that the long-term pressure reduction is mediated through a reduction in vascular resistance. Although multiple lines of evidence suggest that salt and water loss is an essential part of the mechanism, at least in some cases an indirect vasodilator effect may play a role as well. The antihypertensive efficacy of diuretics is proven; they are at least as effective as other classes of antihypertensive drugs. They have been shown to protect against stroke, but not against mortality from myocardial infarction. There is some concern about the metabolic side effects, such as hypokalemia, hyperglycemia, and hyperlipidemia. In order to minimize these side effects the lowest effective dose should be used. Diuretics are likely to remain first-line antihypertensive agents, but they should be considered as one of several possible choices for the initial therapy among other classes, such as beta-blockers, ACE inhibitors, or calcium entry blockers. PMID- 8435379 TI - Pharmacokinetics and pharmacodynamics of torasemide in patients with chronic renal insufficiency--preliminary evaluation. AB - The pharmacokinetics and pharmacodynamics of torasemide were studied in 24 subjects with chronic renal insufficiency. The subjects were divided into two groups of patients, half having a creatinine clearance < 30 ml/min and the other half having a creatinine clearance between 30 and 60 ml/min. Three different intravenous doses were studied in each patient group. Pharmacokinetic analysis revealed dose proportionality when relating area under the concentration curve to dose. There was a progressive decrease in renal clearance of torasemide with declining renal function. In contrast, there was no difference in serum elimination half-life among the patients. In addition, this half-life was not different from that observed in healthy young or elderly control subjects. In previous reports on patients with congestive heart failure and liver disease, serum half-life values were prolonged compared to that of control subjects, presumably due to decreased hepatic, nonrenal clearance of torasemide. Supportive of this hypothesis is the considerably increased area under the serum vs. concentration time curve in such patients. In summary, this study has shown that the serum half-life of torasemide would be unchanged in patients with renal disease. The ceiling dose for torasemide (i.e., the dose above which no further drug-induced natriuresis is obtained) has been preliminarily found to be a single 100-mg intravenous dose in patients with moderate renal insufficiency and a single 200-mg intravenous dose in patients with severe disease. PMID- 8435380 TI - Diuretics in cardiovascular medicine: new wine into old bottles. Presentation of the fundamentals. PMID- 8435381 TI - Torasemide in advanced renal failure. AB - In patients with advanced renal failure, high doses of loop diuretics are required to promote negative sodium and water balance and to treat hypertension. Torasemide is a new loop diuretic that has a high bioavailability of 90% and a plasma half-life of 3-5 hours, which remains unchanged in chronic renal failure. Even in patients with advanced renal failure, intravenous and oral high-dose torasemide proves effective in increasing fluid and sodium excretion in a dose dependent manner. A number of studies in renal failure patients provide evidence that, on a weight-by-weight basis, the ratio of diuretic potency between torasemide and furosemide is 1:2.5 after oral dosing and 1:1 after intravenous administration. The lack of a substantial calciuretic effect of torasemide in chronic renal disease needs further confirmation. Two controlled multicenter clinical trials comparing high oral doses of furosemide and torasemide in patients with end-stage renal disease requiring maintenance hemodialysis demonstrated a substantial increase in urinary volume and electrolyte excretions in patients receiving 100 or 200 mg oral torasemide once daily. A dose of 200 mg oral torasemide appears equally natriuretic to oral furosemide 500 mg, whereas the antihypertensive effect of torasemide is more pronounced. Neither torasemide nor furosemide in the above doses has a negative influence on the neurological status of hemodialysis patients. PMID- 8435382 TI - Torasemide in the treatment of patients with cirrhosis and ascites. AB - The effects of torasemide (20 mg/day) and furosemide (50 mg/day), each given over 4 days, were compared in a randomized and crossover study carried out in seven patients with cirrhosis and tense ascites. Patients also received a low-sodium (40 mmol/day) diet and the aldosterone antagonist, potassium canrenoate (100 mg b.i.d.). Torasemide induced a remarkably higher natriuretic (120 +/- 15 vs. 33 +/ 6 mmol/day, p < 0.02) and diuretic (1450 +/- 63 vs. 900 +/- 58 ml, p < 0.005) effect than furosemide. Body weight loss was also significantly higher (2.5 +/- 1.6 vs. 0.2 +/- 1.3 kg, p < 0.01) during the torasemide period. Kaliuresis was similar during the two treatment periods, despite the striking differences observed in natriuresis. Neither torasemide nor furosemide induced any significant change in serum electrolyte or creatinine concentrations, or in ammonia levels. The results of this study indicate that torasemide is suitable for the treatment of sodium retention in patients with cirrhosis and ascites. PMID- 8435383 TI - A negative association of schizophrenia with an allele of the HLA DQB1 gene among African-Americans. AB - Using polymorphisms of the human leukocyte antigen (HLA) DQB1 gene, a case control study was conducted in a group of patients with schizophrenia (DSM-III, n = 58) and psychiatrically normal controls matched for ethnicity (n = 72), living in the same geographical area. A significant negative association of allele HLA DQB1*0602 with schizophrenia was present among African-Americans (odds ratio 0.19), but could not be detected in Caucasians. PMID- 8435384 TI - Evidence for a gender bias in epidemiological studies of schizophrenia. AB - A higher lifetime morbidity risk for schizophrenia in males has been observed by several investigators. Studies controlled for errors in patient selection and other sources of artefacts, however, find an equal risk in both sexes. In order to detect the causes for the underrepresentation of women in many studies, sample composition of multicentre WHO studies was analysed. Severity of symptoms was not found to be responsible for imbalances in the male/female ratios, but cultural influences and design characteristics were: due to the scarcity of psychiatric facilities, women are less likely to receive adequate treatment in most of the developing countries investigated, since they are kept longer at home and seen by traditional healers in some cultures. Also, studies with an upper age limit of 44 years (according to DSM-III) exclude a greater proportion of female than male schizophrenic patients, and there is some evidence that schizophrenia is more often underdiagnosed in women than in men at least in some countries. Implications for future research on gender differences in schizophrenia are discussed. PMID- 8435385 TI - Abnormal serine-glycine metabolism in the brains of schizophrenics. AB - The metabolism of serine and glycine as studied in the plasma is abnormal in schizophrenics and psychotics. There is a concomitant abnormality of the enzyme serine hydroxymethyl transferase (SHMT). To study the status of serine-glycine metabolism in brains of schizophrenics and controls, frozen autopsied brain tissues were obtained from medial and lateral temporal lobes. The results show that the apparent Km of SHMT and the concentrations of serine and glycine are significantly higher only in the medial temporal lobe areas of schizophrenics when compared to controls. These findings are discussed in the context of the role of glycine and serine as enhancers of glutamatergic excitotoxicity and consequent development of morphological abnormalities in the brains of schizophrenics. PMID- 8435386 TI - Altered fronto-central PINV topography and the primary negative syndrome in schizophrenia. AB - Postimperative negative variation (PINV) was recorded during a warned reaction time paradigm in 16 chronic DSM-IIIR schizophrenics in remission. Clinical symptoms were assessed by BPRS, SANS and the anhedonia scale of the Chapman Questionnaire. Ten healthy controls were studied in the same manner. Over the fronto-central area we found a significantly elevated PINV amplitude with an altered topographical distribution in the patient group. The difference values 'PINV Cz-PINV Fz' were correlated negatively with primary negative symptoms of schizophrenia. PMID- 8435387 TI - The anatomy of the P lymphocyte. AB - This paper describes the basic morphologic criteria for identifying the P lymphocyte. The P cell is a stimulated atypical lymphocyte that is found in schizophrenics and some of their relatives. This cell is suggested as a tentative laboratory indicator of the schizophrenia process. The main identifying features of the cell are its high cytoplasmic basophilia and leptochromatic nuclear structure. Furthermore, the cytoplasm often contains vacuoles and the nuclear shape is often irregular with one or more nucleoli visible. Color micrographs are used to illustrate the cell features. PMID- 8435388 TI - Visual imagery and visual semantics in the cerebral hemispheres in schizophrenia. AB - Divided visual field tasks were given to normal subjects, and patients with schizophrenia and affective disorder, to investigate hemisphere differences in the visual processing of standardised pictorial stimuli. There were two conditions: in the first, subjects were asked to decide whether a common entity represented by a picture was living or non-living, a task involving a categorical judgement based on semantic information; a left hemisphere task. In the second condition, subjects judged whether these depictions represented entities which were bigger or smaller than a cat; a right hemisphere task requiring visual imagery to compare spatial dimensions. It was found that the patient groups, while showing slower reaction time (RT) overall, both displayed a right hemisphere (RH) advantage on the imagery task. Furthermore, the schizophrenics' RHs showed the normal relationship between closeness of size comparison and RT, additional evidence that the visual imagery mechanism is intact. However, these patients failed to show the expected left hemisphere advantage on the visual semantic task. There was a suggestion that performance on the semantic task was related to the experience of vivid imagery in normals and visual hallucinations in the schizophrenics. The possible contribution of hemispheric imbalance in the production of visual hallucinations from a disordered semantic system is discussed. PMID- 8435389 TI - Diabetes, glaucoma, sex, and cataract. PMID- 8435390 TI - Relationship of regression pattern to recurrence in retinoblastoma. AB - A retrospective analysis has been conducted of regression patterns following treatment of retinoblastoma by external beam irradiation. There were 180 tumours in 105 eyes of 83 patients. Type I regression was found to be the commonest pattern and occurred in 50% of cases. Initial tumour size was found to be the only statistically significant determinant of regression pattern (p < 0.01). Thirteen tumours (7%) recurred within a median interval to recurrence of 12 months. All recurrences occurred within 40 months of completion of treatment and none occurred after age 4 years. No tumour less than 6 mm in diameter recurred. Although 10 out of 13 recurrences were of Type I, Cox model regression analysis showed initial tumour size to be the only independent predictor of recurrence (p < 0.01). PMID- 8435391 TI - Prevalence of glaucoma in the west of Ireland. AB - County Roscommon in the west of Ireland is a relatively remote rural area whose population of 55,000 is served by two community medical ophthalmologists and three optometrists. Eye surgical services are not available within the county. In order to assess the needs of the community for prevention of blindness from glaucoma, a simple random sample of the population of County Roscommon was taken for a community based glaucoma survey. A total of 2186 people over the age of 50 were examined which represented a 99.5% response rate. The high response rate was achieved by the community basis of the study and vigorous follow up of non attenders. Intraocular pressure was measured using applanation tonometry, disc evaluation by both direct ophthalmoscopy and stereoscopic biomicroscopy, and visual field analysis using the Henson CFS 2000 and experimental computer controlled video perimetry. Diagnostic criteria were consistent with the preferred practice pattern of the American Academy of Ophthalmology. A crude prevalence of approximately 2% for primary open angle and normal tension glaucoma was found. The population profile of intraocular pressure showed a pattern which decreased with increasing age unlike the Framingham and Ferndale studies but similar to Japanese data. PMID- 8435392 TI - Diabetes, glaucoma, sex, and cataract: analysis of combined data from two case control studies. AB - Data from two case control studies in Oxfordshire were combined and analysed. The combined study covered 1940 subjects, 723 cases, and 1217 controls, between the ages of 50 and 79 with a response rate of 97% for cases and 94% for controls. Diabetes was shown to be a powerful and highly significant risk factor for cataract with a relative risk of 5.04. More than 11% of cataracts in Oxfordshire are attributable to diabetes. The relative risk did not increase significantly with age within the range 50 to 79 years but was higher in females than in males. For females with diabetes the relative risk was 7.85 with 95% confidence interval from 4.30 to 14.3 compared with 3.42 with confidence interval from 2.05 to 5.71 for males with diabetes. Diabetes remained a powerful risk factor when other identified risk factors had been controlled for. No known mechanism for the development of diabetic complications provides an explanation for the excess risk in females. Combination of the two studies led to better estimates of the relative risk of glaucoma as a risk factor for cataract (3.96 with 95% confidence interval from 2.35 to 6.68). The relative risk appeared to be greater in women than in men but this difference was not statistically significant. There was no significant change in risk with age. Glaucoma is a powerful and independent risk factor for cataract in both sexes and may be responsible for 5% of all cataracts in our area. PMID- 8435393 TI - Reproducibility of transcranial Doppler ultrasound examinations of the ophthalmic artery flow velocity. AB - Transcranial Doppler ultrasound measurements of ophthalmic artery velocity were made on 88 patients predominantly suffering from glaucoma. Of the four observed parameters, peak velocity, mean-enveloped velocity, diastolic velocity, and resistivity index, the latter was found to be the most reproducible (CV = 5.2%). The variability between patients was approximately twice that of the variability between consecutive measurements. Measurement error appeared to decrease as the operator gained experience. PMID- 8435394 TI - Ophthalmic artery flow velocity in glaucomatous and normal subjects. AB - The velocity of blood flow in the ophthalmic artery was measured with a transcranial Doppler ultrasound (2 MHz). Sixty patients with chronic open angle glaucoma (COAG), 42 patients with normal tension glaucoma (NTG), and 35 normals were studied. Peak flow velocity (peak), mean-enveloped velocity (mean) and diastolic velocity were compared in the three groups. The COAG patients and the NTG patients showed a significant reduction of all three Doppler flow velocities compared with the normals (COAG vs normal, p = 0.013, 0.019, and 0.009; NTG vs normal, p = < 0.001, < 0.001, and < 0.001 for peak, mean and diastolic flow velocity respectively). The NTG patients also had a significant slower mean flow velocity than the COAG patients (p = 0.016), but not for peak and diastolic flow velocities (p = 0.060 and 0.052 respectively). Based on ophthalmic flow velocity values, many NTG patients and a few COAG patients had slower flow velocities than the normals. The significance of these haemodynamic differences is not yet known. PMID- 8435395 TI - Visual loss in an onchocerciasis endemic community in Sierra Leone. AB - The visual acuities of 1625 individuals recruited to a community-based clinical trial of ivermectin in southern Sierra Leone were measured, and the prevalence of visual loss in this rural population where onchocerciasis is hyperendemic was determined. Ocular examination was performed before treatment to establish the cause of visual loss. Using WHO definitions, 1.3% were blind (less than 3/60 in both eyes), 4.3% were visually impaired (between 6/24 and 3/60 in the better eye), and a further 3.4% were uniocularly blind (less than 3/60 in one eye and better than 6/24 in the other). Cataract and onchocerciasis were the major causes of visual loss in this population. More than half of the ocular morbidity was preventable or treatable by public health measures or basic curative medicine. These findings are discussed in the light of the available health and eye care services. PMID- 8435396 TI - Choroidal rupture and optic atrophy. AB - The association between post-traumatic optic disc pallor and traumatic choroidal rupture is poorly understood. To further define this relationship, nine cases of indirect traumatic choroidal rupture and post-traumatic optic disc pallor were compared with cases of indirect choroidal rupture without disc pallor in terms of severity of ocular injury, fundus findings, and visual outcome. The type and severity of the injury did not appear to influence the risk of optic disc pallor. Optic disc pallor was associated with a slightly poorer long term visual acuity than eyes without pallor (p = 0.059). The presence of a relative afferent pupillary defect was strongly associated with optic disc pallor (p = 0.016). Peripapillary retinal pigment epithelial abnormalities were a common finding, suggesting peripapillary trauma as a cause for optic disc pallor. PMID- 8435397 TI - Cataract development and outcome of surgery in bone marrow transplanted children. AB - Cataract development in bone marrow transplanted (BMT) patients was studied prospectively. There were 61 children, transplanted before the age of 18 years, who survived more than 1 year after transplantation. Patients transplanted for leukaemia (n = 43) were conditioned before BMT with cyclophosphamide (Cy) and total body irradiation (TBI). Patients with severe aplastic anaemia (SAA) (n = 9) only received Cy. None of the patients with SAA developed cataracts. All children with leukaemia, who were followed for at least 3 years (n = 37), developed lens posterior subcapsular cataracts (PSC). Cataract extraction was performed in 28 eyes, on average 5.1 years (range 3-9 years) after BMT. Postoperative corrected visual acuity was similar to that before BMT. The majority of cases needed laser capsulotomy within 2 years after cataract extraction. TBI seems to be the main cause for the high incidence of cataract after BMT. A relationship to steroid administration could not be proved, but a contributory effect is not excluded. PMID- 8435398 TI - Increased D-arabinitol/creatinine ratio in sera of patients with Behcet's disease during an active phase. AB - The ratios of D-arabinitol (a major metabolite of Candida species) to creatinine were examined in 46 sera of 40 patients with ocular inflammatory disease and in 50 age-matched normal controls (25 men and 25 women). The mean ratio in patients with endogenous Candida endophthalmitis was higher than in the normal controls. Seven samples taken from patients with Behcet's disease during an active phase showed higher values than in the controls. Fourteen patients with Behcet's disease in remission showed D-arabinitol/creatinine values within normal range. In four patients with sarcoidosis, in two patients with Vogt-Koyanagi-Harada disease, and in 16 patients with bilateral uveitis of an unknown cause, the ratios were within normal range. It is possible that D-arabinitol, or a metabolite of Candida species, may be related in part to the active phase of Behcet's disease. PMID- 8435399 TI - Microbial contamination of contact lens cases in the west of Scotland. AB - A cross-sectional study of 178 asymptomatic contact lens wearers attending 10 contact lens practices in the west of Scotland was conducted over a 4 month period. The aims of the study were to identify specific microbial contaminants in lens cases, to determine the rate of contamination of such containers and to assess the value of the steps involved in different lens care regimens in the prevention of case contamination. Microbial contamination affected 53% of lens cases. Cases used with conventional wear and disposable systems were contaminated at similar rates and, therefore, the advantage of regular lens replacement may have been lost if these lenses were stored in contaminated cases. Four percent of lens cases were contaminated with amoebal species and all of these showed concomitant bacterial colonisation. These findings imply that case hygiene is probably as important as lens hygiene if new or disinfected lenses are not to be immediately re-contaminated by storage in dirty cases. Unfortunately simple and effective methods of lens and case disinfection, which would be suitable for use in the average home environment, are not yet available. It follows that frequent and regular disposal of lens cases may prove to be a necessary measure to prevent the build-up of microbial colonisation in such containers. PMID- 8435400 TI - Pinealitis accompanying equine recurrent uveitis. AB - There is no direct verification of pineal gland involvement in human uveitis. Specimens of pineal tissue are not available during active uveitis in human patients. Naturally occurring uveitis in horses gives us an opportunity to examine tissues during active ocular inflammation. We examined the pineal gland of a horse that was killed because it had become blind during an episode of uveitis. The clinical history and histopathology of the eyes were consistent with post-leptospiral equine recurrent uveitis. The pineal gland of this horse had significant inflammatory infiltration consisting mainly of lymphocytes with some eosinophils. This observation of pinealitis accompanying equine uveitis supports the animal models of experimental autoimmune uveoretinitis with associated pinealitis and suggests that the pineal gland may be involved in some human uveitides. PMID- 8435402 TI - Monostotic fibrous dysplasia of the orbit: an unusual lacrimal fossa mass. AB - A case of monostotic fibrous dysplasia involving the orbit, presenting with a short history of painful, progressive proptosis and a lacrimal fossa mass is reported. There were no clinical or radiological clues to the diagnosis which was made on frozen section at the time of open surgical biopsy. The features of orbital fibrous dysplasia are reviewed and a possible mechanism for this rare clinical presentation of fibrous dysplasia is discussed. PMID- 8435401 TI - Disease and risks associated with contact lenses. PMID- 8435403 TI - Early treatment of juvenile xanthogranuloma of the iris with subconjunctival steroids. AB - Five infants with biopsy proved juvenile xanthogranuloma of the iris were reviewed. Early treatment with subconjunctival injection of steroids and topical steroid drops resulted in regression of the lesion in four patients. One patient, reviewed at the age of 8 months after glaucoma which had developed secondary to the iris xanthogranuloma, had been treated by surgery alone: the visual outcome was very poor. PMID- 8435404 TI - Sporothrix schenckii endophthalmitis presenting as granulomatous uveitis. AB - Sporothrix schenckii occurs worldwide as a chronic subcutaneous mycotic infection, but can result in intraocular infection of cryptogenic origin without evident systemic infection. A case of S schenckii endophthalmitis is presented without a history of trauma or systemic infection originally diagnosed as granulomatous uveitis that resulted in scleral perforation. PMID- 8435405 TI - Spontaneous congenital epithelial iris cysts. PMID- 8435406 TI - Loss of contrast sensitivity in diabetic patients with LOCS II classified cataracts. AB - Contrast sensitivity function (CSF) was assessed in a population of diabetics with moderate cataracts to determine if CSF testing provides more information about visual dysfunction than Snellen or Lotmar interferometric visual acuity. With the Lens Opacities Classification Systems Version II (LOCS II) of cataract classification it was possible to grade accurately the type and severity of cataract and nuclear brunescence. The presence of statistically significant relationships between increasing LOCS II classification (worsening cataract) and diminished function, even when the regression model was controlled for Snellen visual acuity, supports the thesis that CSF measurements do provide more information about cataract related visual loss than Snellen acuity alone. Statistically significant (p < or = 0.05) relationships existed between different morphological types of cataract, nuclear colour, and CSF at specific frequencies. The frequencies affected differed with cataract type or nuclear colour, and with distance and near CSF. PMID- 8435407 TI - Orbital volume measurement in the management of pure blowout fractures of the orbital floor. AB - With the recent advent of accurate orbital volume assessment by computed tomography, a retrospective analysis was made of 31 patients with 'pure' blowout fracture of the orbital floor, managed either surgically or conservatively, to determine whether orbital volume measurement could provide an additional parameter of use in the management of such fractures. There was a significant difference in orbital volume discrepancy between patients managed surgically or conservatively suggesting that this investigation may be of use in decision making on surgical intervention in patients with orbital blowout fractures. PMID- 8435408 TI - Direct clinico-histological correlation of parapapillary chorioretinal atrophy. AB - Parapapillary chorioretinal atrophy is a morphological feature of glaucomatous optic nerve damage since it occurs more often and is larger in glaucomatous eyes than in normal eyes. This study was undertaken to find the histological correlation. Optic disc photographs and histological sections through the optic disc of 21 human eyes enucleated because of malignant uveal melanoma were morphometrically evaluated. Seventeen eyes had normal intraocular pressure and four eyes showed elevated intraocular pressure and glaucomatous optic disc cupping. Ophthalmoscopically, the parapillary chorioretinal atrophy was divided into zone 'alpha', located peripherally and characterised by irregular hypopigmentation and hyperpigmentation, and zone 'beta' located close to the optic disc border and showing visible sclera and visible large choroidal vessels. Histologically, zones 'A' and 'B' were differentiated. Zone 'A' peripheral to zone 'B' showed irregularities in the retinal pigment epithelium. It consisted of an unequal distribution of melanin granules and partial atrophy of cells. In zone 'B' adjacent to the optic disc, Bruch's membrane was bared of retinal pigment epithelium cells and the photoreceptors were markedly reduced in density or were completely missing. In a direct clinical histological comparison, zone 'A' correlated significantly with zone 'alpha' (r = 0.66; p < 0.01), and zone 'B' correlated with zone 'beta' (r = 0.99; p < 0.0001). Zone 'A', 'B', 'alpha' and 'beta' were larger in the four glaucomatous eyes than in the normal ones. The findings indicate that zone 'beta' represents histologically a complete loss of retinal pigment epithelium cells and an incomplete loss of adjacent photoreceptors. Zone 'alpha' may be the histological correlate of irregularities in the retinal pigment epithelium. PMID- 8435409 TI - Detection of Toxoplasma gondii in aqueous humour by the polymerase chain reaction. AB - Ocular toxoplasmosis is the most frequent infectious cause of chorioretinal inflammation in immunocompetent patients. Nowadays, the biological diagnosis of ocular toxoplasmosis requires serological tests and anterior chamber puncture to detect the local production of specific antibodies. A new technique is described to detect Toxoplasma in aqueous humour by a polymerase chain reaction in which the target is a specific ribosomal DNA segment. Sixty eight patients (71 eyes) were included; 59 (83%) eyes were suspected of having ocular toxoplasmosis. Of these 59 eyes, 15 (25.4%) had characteristic fundus lesions with obvious intraocular inflammation signs and 44 (75%) had retinal scar of ocular toxoplasmosis without clinically detectable inflammation. Twelve (17%) eyes had uveitis of non-Toxoplasma origin and constituted the control group. The parasite was present in aqueous humour in 20 (33.8%) cases. No false positives were detected. The sensitivity of the test is reduced by the low numbers of the sample. The combination of this technique with Witmer-Desmonts coefficient increases the probability of making a biological diagnosis of ocular toxoplasmosis. The physiopathological value of this technique is emphasised and the presence of tachyzoites in the anterior chamber is suggested. This should be a very promising technique for the diagnosis of ocular toxoplasmosis. PMID- 8435410 TI - The EP2 receptor is the predominant prostanoid receptor in the human ciliary muscle. AB - Prostaglandins can reduce intraocular pressure by increasing uveoscleral outflow. We have previously demonstrated that the human ciliary muscle was a zone of concentration for binding sites (receptors) for prostaglandin F2 alpha and for prostaglandin E2. Here, we try to elucidate the types of prostanoid receptors in the ciliary muscle using competitive ligand binding studies in human eye sections and computer assisted autoradiographic densitometry. Saturation binding curves showed that the human ciliary muscle had a large number of binding sites with a high affinity for prostaglandin E2 compared with prostaglandin D2 and F2 alpha. The binding of tritiated prostaglandin E2 and F2 alpha in the ciliary muscle was displaced most effectively by prostaglandin E2 and 11-deoxy prostaglandin E1 (a selective EP2 prostanoid receptor agonist), whereas the binding of prostaglandin D2 was displaced most effectively by prostaglandin E2 and D2. These results indicate that the dominant prostanoid receptor in the human ciliary muscle is the EP2 subclass and that there is also a small number of DP receptors. PMID- 8435411 TI - The chi 2 test for data collected on eyes. PMID- 8435412 TI - Churg-Strauss vasculitis presenting with severe visual loss due to bilateral sequential optic neuropathy. AB - A 44-year-old man with severe visual loss due to an acute bilateral sequential optic neuropathy is described, where the associated pulmonary disease and peripheral eosinophilia led to a diagnosis of Churg-Strauss syndrome (allergic angiitis). The mechanism of the optic neuropathy was most probably acute ischaemia of the anterior optic nerve due to direct involvement of the short posterior ciliary arteries by inflammatory disease of the vessel wall. PMID- 8435413 TI - Secondary retinitis pigmentosa and cerebral demyelination in Lyme borreliosis. AB - A 15-year-old girl developed retinitis pigmentosa-like fundus changes in the left eye and optic neuropathy in the right eye as well as cerebral demyelination as a result of late Lyme borreliosis (LB). The diagnosis was confirmed by polymerase chain reaction, which detected a Borrelia burgdorferi specific segment of a gene coding for 41 kD endoflagellin, both in the vitreous and the cerebrospinal fluid. The diagnosis was delayed because testing for Borrelia antibodies in serum and cerebrospinal fluid yielded negative results. However, later on, another laboratory reported the antibodies of the patient's pretreatment serum to be positive for LB. PMID- 8435414 TI - Two cases of coloboma associated with unbalanced translocations. AB - Two cases of coloboma are recorded, both secondary to previously unreported unbalanced translocations. These cases underline the association of chromosomal abnormalities and coloboma, particularly when accompanied by systemic abnormalities. They also highlight the importance of a full systemic assessment of coloboma patients and adequate genetic counselling for both patients and their families. PMID- 8435415 TI - Spontaneous development of retinal ischaemia and rubeosis in eyes with retinal racemose angioma. AB - Two Cases are described of spontaneous vascular closure occuring in eyes with arteriovenous malformations, causing visual loss due to retinal ischaemia and rubcosis iridis. PMID- 8435416 TI - Ocular involvement in mycosis fungoides. AB - A case of mycosis fungoides with bilateral intraocular involvement is reported. The diagnosis was established with the aid of a vitreous biopsy. Intraocular involvement, though rare, may be an early sign of extracutaneous disease. PMID- 8435417 TI - Acanthamoeba and contact lens disinfection: should chlorine be discontinued? PMID- 8435418 TI - Corneal diameter in premature infants. PMID- 8435419 TI - The Farnsworth-Munsell 100 hue test and optic neuritis. PMID- 8435420 TI - Trachoma--the future for a disease of the past. PMID- 8435421 TI - The Farnsworth-Munsell 100 hue test in the first episode of demyelinating optic neuritis. AB - The Farnsworth-Munsell 100 hue test (F-M 100) was used to examine 30 patients with their first episode of unilateral demyelinating optic neuritis (DON) at presentation, after 6 weeks and after 6 months. Twelve patients satisfactorily completed the test with the affected eye at presentation. This number had increased to 23 by 6 weeks and to 27 by 6 months. No patient with a visual acuity of LogMAR 0.86 (Snellen equivalent approx 6/43) or worse, could complete the test. The mean total error score of affected eyes showed significant improvement at each subsequent examination but was always worse than the non-affected eyes. There was a significant correlation between total error scores and visual acuities of affected eyes at presentation and after 6 months. Fourteen patients recovered a visual acuity of LogMAR 0.0 (Snellen equivalent 6/6) or better but the total error scores of the affected eyes were significantly worse than the non affected eyes (p = 0.017), indicating that defective colour vision is an indicator of a previous episode of DON despite the recovery of normal visual acuity. DON is reported to produce a red-green (Type II) axis of colour defect but individual F-M 100 polar diagrams were usually generally abnormal and did not show any predominance of recognisable axis of colour defect at any examination. Group averaging of the F-M 100 data from such a well-defined group of patients with acute DON revealed a significant bipolar abnormality in the tritan (blue yellow) axis at presentation which was not demonstrated at the subsequent examinations or at any examination of the non-affected eyes. PMID- 8435422 TI - Clinical and infrared pupillometry in central retinal vein occlusion. AB - Measurements of pupillary reactivity and size were recorded using neutral density filters and infrared pupillometry (IRP) in a prospective masked study of acute central retinal vein occlusion (CRVO) to quantify the two methods of measurement and to compare their value in the prediction of rubeosis. Thirty two patients were examined within 45 days of disease onset. The mean relative afferent pupillary defect (RAPD) with filters was significantly greater in patients who developed rubeosis than in those who did not (0.9 vs 0.3 log units; p = 0.012). Using IRP, the pupillary diameters in the dark (maximum) and in the light (minimum) were significantly greater, the rate of pupillary constriction was significantly lower, and the latency of constriction was significantly greater in affected eyes than in unaffected eyes. The differences between affected and unaffected eyes in the IRP parameters of latency, rate, maximum, and minimum pupillary diameters were significantly greater in patients who developed rubeosis than in those who did not. Discriminant analysis of the IRP parameters correctly and statistically significantly identified rubeotic patients with 83% sensitivity and 95% specificity. An RAPD of > or = 0.6 log units was 83% sensitive and 70% specific in this regard. It is concluded that pupillary reactions are abnormal in many patients with acute CRVO, as measured by both pupillometric methods. The degree of these abnormalities has a relationship to the development of rubeosis, and might prove useful in planning the follow up of these patients or in deciding whether to apply panretinal photocoagulation. The neutral density filter test is readily available but subjective. IRP is more specific, objective, and suited to further development, but requires sophisticated equipment. PMID- 8435423 TI - Results of community-based eyelid surgery for trichiasis due to trachoma. AB - In many parts of Africa patients with upper-lid trichiasis due to trachoma have very limited access to ophthalmologists or hospital facilities. In order to reach these patients it is necessary for trained paramedical eye workers to operate on patients close to where they live. The results of trichiasis surgery performed by an ophthalmic nurse in Tanzania were evaluated. A total of 156 operations were performed on 94 patients over a 2 year period by an eye nurse in central Tanzania. One hundred and forty four eyes in 86 patients were followed for a minimum of 9 months (range 9-36; mean 25.5 months). One eye developed a wound infection and nine eyes developed minimal central notching of the upper eyelid, but without corneal exposure. Survival time analysis showed a probability of survival without recurrent trichiasis of 81% at 24 months (95% CI 74% to 88%) and 79% at 36 months (95% CI 71% to 87%). It is concluded that trichiasis surgery may be safely and effectively performed in the community by a trained ophthalmic nurse. PMID- 8435424 TI - Retinitis pigmentosa, ataxia, and mental retardation associated with mitochondrial DNA mutation in an Italian family. AB - An Italian pedigree including two sisters and their mother affected by a neuro ophthalmic disease characterised by retinitis pigmentosa, ataxia, and psychomotor retardation is reported. Molecular analysis of mitochondrial DNA showed the presence of heteroplasmic 8993 point mutation in the subunit 6 of the ATPase gene. The clinical features and genetic findings in this family were comparable with those recently described in an English family. The mitochondrial DNA analysis of the family showed a correlation between the amount of mutated DNA and the disease severity in the probands, and indicated the presence of a threshold amount of mutated genome inducing ophthalmic defects. Moreover, the comparative analysis of blood, hairs, muscle, and urinary tract epithelia of two probands revealed an essentially similar distribution of mutated and wild type mitochondrial genomes. Our results suggest that the 8993 mitochondrial DNA mutation characterises a disease with similar clinical features in different populations. PMID- 8435425 TI - Influence of alpha thalassaemia on the retinopathy of homozygous sickle cell disease. AB - Homozygous alpha+ thalassaemia (alpha-/alpha-) ameliorates some of the clinical manifestations of homozygous sickle cell (SS) disease but its effect on retinal complications remains unknown. This has been assessed by visual examination and fluorescein angiography in 39 subjects with SS disease and homozygous alpha+ thalassaemia and in 39 age/sex matched controls with SS disease but with a normal alpha globin genotype (alpha alpha/alpha alpha). The results indicate that homozygous alpha+ thalassaemia reduces the extent of peripheral retinal vessel closure but has no apparent effect on the frequency of proliferative sickle retinopathy. PMID- 8435426 TI - Follow-up study on premature infants with and without retinopathy of prematurity. AB - The ocular complications in population of 131 premature infants, with and without retinopathy of prematurity (ROP) are reported. An increased incidence of strabismus (20% with ROP and 25% without ROP) and myopia (27.5% with ROP and 8.8% without ROP) was shown. Significant visual loss occurred in 10.7% overall, increasing to 35% with stage 3 disease and 100% with stage 4. With the increased survival rate of premature infants, the relevance to future management of this expanding group of young people is considered. PMID- 8435427 TI - Activation of human monocytes and alveolar macrophages by a synthetic peptide of C-reactive protein. AB - We have previously shown that native human C-reactive protein (CRP) produces antitumor effects in experimental animals, and that these effects are mediated primarily through macrophages. More recently, we have observed that RS-83277, a synthetic peptide derived from CRP, appears to mimic the antitumor effects of native CRP. The purpose of this study was to determine the effects of RS-83277 on normal human monocyte and alveolar macrophage tumoricidal activity, and cytokine secretion. At optimal doses of 250-500 micrograms/ml, RS-83277 significantly enhanced tumoricidal activity of both monocytes and macrophages. RS-83287, a CRP peptide derived from a different site, had no effect at these doses. Specificity of RS-83277 for monocyte/macrophage-mediated cytotoxic activity was demonstrated by the failure of RS-83277 to enhance either natural killer (NK) or lymphokine activated killer (LAK) cell-mediated activity. RS-83277 also augmented secretion of interleukin-1-beta (IL-1 beta) and interleukin-6 (IL-6) by monocytes. These data suggest a role for synthetic CRP peptide, RS-83277, as a novel biological response modifier in cancer therapy. PMID- 8435428 TI - Specific release of cytokines by lymphocytes infiltrating human melanomas in response to shared melanoma antigens. AB - Lysis of autologous and human leucocyte antigen (HLA)-matched allogeneic melanomas by cultured human tumor-infiltrating leukocytes (TIL) suggests that shared melanoma antigens (Ag) exist and are recognized by TIL in the context of self major histocompatibility complex (MHC) molecules. We have recently shown that cytokine release by TIL is another indicator of the specific interaction with autologous tumor. To determine if recognition of shared melanoma Ag can also induce cytokine release, seven melanoma TIL, which lysed autologous tumor, were co-cultured with autologous tumor or with 7-12 HLA-matched or unmatched melanoma stimulators for 6-24 h. Supernatants were collected and assayed by ELISA for the presence of granulocyte/macrophage colony stimulating factor (GM-CSF), interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-4, and IL-6. Among five of six melanoma TIL for which autologous tumor was available, autologous melanoma cells stimulated specific release of at least one of three cytokines: GM-CSF, IFN-gamma, and TNF-alpha. Neither IL-4 nor IL-6 secretion by three TIL cultures tested was enhanced upon contact with tumor. For six of seven TIL cultures, HLA-matched allogeneic melanomas also stimulated significant cytokine release; HLA-A1, -A2, -A24, -B8, and -Cw7 were identified as possible restriction elements. The cytokine secretion induced by both autologous and allogeneic HLA-matched melanomas could be blocked by an anti-MHC I antibody. These data suggest that cytokines can be specifically released by TIL recognizing a shared melanoma antigen in the context of self MHC molecules. PMID- 8435429 TI - Chemoimmunotherapy of murine liver metastases with 5-fluorouracil in combination with liposome-encapsulated muramyl dipeptide. AB - The therapeutic effect of a combination of liposomal muramyl dipeptide (MDP) and 5-fluorouracil (5FU) was studied in a murine tumor model of hepatic metastases of the tumor cell line C26, a colon adenocarcinoma. Liposomal MDP (250 micrograms/kg body wt) and a low, nontoxic, dose of 5FU (10 mg/kg body wt) were mixed and administered during 6 consecutive days once daily, three times i.v. and three times i.p. Treatment was initiated 4 days after intrasplenic tumor cell injection. The combination of liposomal MDP and 5FU significantly reduced the number of liver metastases and the total tumor load in the liver. Liver weights of tumor-bearing mice treated with the combination were significantly lower than the liverweights of control mice (p < 0.005) and of mice treated with 5FU alone (p < 0.02) or liposomal MDP alone (p < 0.05). Liposomal MDP and 5FU, when given as single treatment modalities, had no significant effect on the number of metastases and liver weight. These results show that liposomal MDP can enhance the therapeutic effect of 5FU for the treatment of liver metastases. PMID- 8435430 TI - Eisenin (L-pyroGlu-L-Gln-L-Ala), a new biological response modifier. AB - Eisenin (L-pyroGlu-L-Gln-L-Ala), a tripeptide extracted from a brown marine alga (Eisenia bicyclis Setchell) showed the immunological activity to augment natural cytotoxicity of peripheral blood lymphocytes (PBLs) in humans. This activity could be seen when it was added directly to 51Cr release assay, and also when PBLs alone were incubated with this compound for 0.5-1 h before addition to the 51Cr release assay. The resulting augmented cytotoxicity can be attributed to natural killer cells because treatment of eisenin-stimulated PBLs with anti-Leu 11b monoclonal antibody (mAb) plus complement completely abolished the augmented cytotoxicity, and, moreover, deletion of Leu 19-positive cells with anti-Leu 19 mAb (mouse IgG1) and anti-mouse IgG-coated magnetic beads showed the same effect. Eisenin could not augment natural cytotoxicity of Sephadex G-10 column-eluted cells. Eisenin rendered K-562 target cells resistant to lysis by PBLs stimulated by eisenin. Both amino acids, L-pyroglutamic acid and L-alanine, as well as a mixture of the three component amino acids of eisenin could augment the natural cytotoxicity. Therefore, it is considered that the structure responsible for the augmentation of natural cytotoxicity by eisenin may be that of the amino acids. PMID- 8435431 TI - A pilot phase II trial of continuous-infusion interleukin-2 followed by lymphokine-activated killer cell therapy and bolus-infusion interleukin-2 in renal cancer. AB - Nine patients with metastatic renal cell carcinoma were entered into a pilot protocol including a 4-week regimen utilizing human recombinant interleukin-2 (IL 2) and in vitro lymphokine-activated killer (LAK) cells. The regimen included 2 weeks (4 days of treatment and 3 days of rest/week) of continuous-infusion (c.i.) IL-2 at 3 x 10(6) U/m2/day, followed by two leukaphereses. LAK cells were cultured in vitro for 48 to 72 h and administered as a single infusion, followed by 9 days of bolus i.v. injections of 10(6) U IL-2/m2/dose, given every 8 hours (t.i.d.). The average (+/- SD) number of LAK cells infused per patient was 7.2 x 10(10) (+/- 3.5 x 10(10)). One patient showed > 50% shrinkage of tumor (lung + renal bed recurrence). Toxicity was similar to that encountered in other studies using similar IL-2 doses and LAK cells and consisted of fever, hypotension, fluid retention, and reversible renal insufficiency. These results indicate that the 2 weeks of IL-2 c.i. provided conditions enabling the harvest of large quantities of mononuclear cells from the peripheral blood of patients; this could be useful for future trials requiring the use of in vitro activated lymphocytes. Nevertheless, these pilot data suggest that this regimen of prolonged t.i.d. IL-2 administration after the LAK infusion does not seem to generate any improvement in antitumor effects from those obtained using other LAK + IL-2 regimens. PMID- 8435432 TI - Intrathecal administration of interleukin-2 for meningeal carcinomatosis due to malignant melanoma: sequential evaluation of intracranial pressure, cerebrospinal fluid cytology, and cytokine induction. AB - A patient with interleukin (IL)-2 responsive metastatic melanoma developed meningeal carcinomatosis. Treatment was attempted with intrathecal (i.t.) IL-2 (5 weekly doses of 3-6 x 10(6) IU) without glucocorticosteroids. Marked increases in cerebrospinal fluid (CSF) pressure occurred 5-10 h following each IL-2 dose, resulting in reversible abnormalities of neurologic function. IL-2 clearance from the CSF ranged from 21 to 85 ml/h, with an apparent first order rate constant of 0.08-0.23 hr-1. These values were consistent with clearance by bulk flow mechanisms. Clearance also correlated directly with peak CSF pressure. Progressive increases in CSF tumor necrosis factor (TNF)-alpha and IL-6 levels, but not Il-1 alpha, were also noted over successive treatment cycles. Increasing neutrophilia (peaking at 12 h postdose) and a delayed lymphocytosis and monocytosis (at 20-30 h) were observed with each successive i.t. IL-2 dose. Activated lymphocytes were not observed in the CSF, however, suggesting that an exogenous source of activated lymphokine-activated killer (LAK) cells may be helpful in obtaining effective antitumor responses. PMID- 8435433 TI - Antitumor effect of thymosin alpha 1/interleukin-2 or thymosin alpha 1/interferon alpha,beta following cyclophosphamide in mice injected with highly metastatic Friend erythroleukemia cells. AB - We investigated the effects of the systemic administration of thymosin alpha 1 plus relatively low doses of human recombinant interleukin-2 or very low doses of interferon alpha,beta in untreated and cyclophosphamide (CY)-treated DBA/2 mice challenged either subcutaneously or intravenously (i.v.) with Friend erythroleukemia cells (FLC). Both treatments resulted in the complete regression of subcutaneous tumor and cured a significative percentage of mice. They also increased the survival time of mice i.v. injected with large numbers of FLC. Neither immunotherapy alone nor CY, alone or in combination with single cytokines, produced similar effects. The antitumor action of these combined chemoimmunotherapy protocols seems to involve activation of the immune response since (a) a synergistic increase of the cytotoxicity of spleen cells was demonstrated in treated mice; (b) selective in vivo depletion of asialo-GM1, CD4, or CD8-positive cells abrogated this antitumor activity; and (c) a high lymphoid cell infiltration was found at the tumor site and in the livers of treated mice. PMID- 8435434 TI - The bacterial energy-transducing NADH-quinone oxidoreductases. PMID- 8435435 TI - Small subunits of Photosystem I reaction center complexes from Synechococcus elongatus. II. The psaE gene product has a role to promote interaction between the terminal electron acceptor and ferredoxin. AB - Function of a subunit polypeptide (the psaE gene product) of Photosystem I (PS I) reaction center complexes was investigated by comparing the reactivity of the reduced iron-sulfur centers (FA/FB)- with ferredoxin among Synechococcus PS I complexes which had been variously depleted of this polypeptide. Ferredoxin at or below 1 microM can accept electrons from (FA/FB)- effectively competing with the back reaction between P-700+ and (FA/FB)- in the thylakoid membranes and PS I complexes that contained all the eight small subunits. The high reactivity of (FA/FB)- with low concentrations of ferredoxin was observed in PS I complexes which contain only the products of psaC, psaD and psaE genes but not in complexes which carry the psaC, psaD, psaL and psaK gene products but no psaE gene product. Varied amounts of the psaE gene product were extracted by treatment with different concentrations of a cationic detergent, dodecyltrimethylammonium bromide, and 2.5 M NaCl. The solubilized polypeptide was then reconstituted to the depleted complexes. The magnitudes of the back reaction that could be suppressed by addition of ferredoxin at or below 1 microM were well correlated to the amounts of the psaE polypeptide remained bound or rebound to the complexes. It is concluded that the product of the psaE gene has a role to promote the interaction between the terminal bound electron acceptor and ferredoxin. A high autooxidizability of (FA/FB)- and contrasting effects of lipophilic cations and anions on the rate of the back reaction from (FA/FB)- to P-700+ were also reported. PMID- 8435436 TI - Developmental changes in the respiratory chain of Ascaris mitochondria. AB - The Ascaris larval respiratory chain, particularly complex II (succinate ubiquinone oxidoreductase), was characterized in isolated mitochondria. Low temperature difference spectra showed the presence of substrate-reducible cytochromes aa3 of complex IV, c+c1 and b of complex III (ubiquinol-cytochrome c oxidoreductase) in mitochondria from second-stage larvae (L2 mitochondria). Quinone analysis by high-performance liquid chromatography showed that, unlike adult mitochondria, which contain only rhodoquinone-9, L2 mitochondria contain ubiquinone-9 as a major component. Complex II in L2 mitochondria was kinetically different from that in adult mitochondria. The individual oxidoreductase activities comprising succinate oxidase, and fumarate reductase were determined in mitochondria from L2 larvae, from larvae cultured to later stages, and from adult nematodes. The L2 mitochondria exhibited the highest specific activity of cytochrome c oxidase, indicating that L2 larvae have the most aerobic respiratory chain among the stages studied. The Cybs subunit of complex II in L2 and cultured larvae mitochondria exhibited different reactivities against anti-adult Cybs antibodies. Taken together, these results indicate that the complex II of larvae is different from its adult counterpart. In parallel with this change in mitochondrial biogenesis, biosynthetic conversion of quinones occurs during development in Ascaris nematodes. PMID- 8435437 TI - Skeletal muscle mitochondrial beta-oxidation of dicarboxylates. AB - (1) The oxidation of [U-14C]hexadecanedionoyl-mono-CoA by rat skeletal muscle mitochondrial fractions is carnitine dependent and is inhibited by cyanide. (2) [U-14C]hexadecanedionoyl-mono-CoA was oxidised at a rate 8% of that of [U 14C]hexadecanoyl-CoA. (3) Oxidations were saturable and no substrate inhibition was observed. (4) We demonstrate the formation of dicarboxylyl-mono-CoA esters and the corresponding carnitine derivatives. (5) We conclude that, although skeletal muscle mitochondria are capable of the beta-oxidation of dicarboxylic acids, this is unlikely to be of great physiological significance. PMID- 8435438 TI - Relationships between age-dependent changes in the effect of almitrine on H(+) ATPase/ATPsynthase and the pattern of membrane fatty acid composition. AB - The effects of almitrine on ATPase/ATPsynthase previously described in beef heart mitochondria (Rigoulet et al. (1990) Biochim. Biophys. Acta 1018, 91-97) are also observed in liver mitochondria isolated from rats older than 7 weeks. In contrast, in rats younger than 5 weeks, almitrine at the same concentration has no effect on the ATPase/ATPsynthase complex. This age-dependent action of almitrine is well correlated with age-dependent modifications of two fatty acids: linoleic and docosahexaenoic acids. The possibility of a change in H+/ATP stoichiometry of the ATPase/ATPsynthase induced by almitrine seems related to more general modifications of membrane properties during growth of the rat. PMID- 8435439 TI - Increase in the level of m-calpain correlates with the elevated cleavage of filamin during myogenic differentiation of embryonic muscle cells. AB - The activity of Ca(2+)-activated proteinase requiring millimolar Ca2+ (m-calpain) was found to increase dramatically in cultured chick embryonic myoblasts during the early period of myogenic differentiation. Furthermore, the protein level of m calpain also markedly increased in parallel with the rise in its activity, and both remained elevated thereafter. On the other hand, the activity level of calpastatin, an endogenous inhibitor of the proteinase, remained similar during the entire period of the culture. In addition, the activity of Ca(2+)-activated proteinase requiring micromolar Ca2+ (mu-calpain) was not detected in either proliferating or differentiated myoblasts. Thus, the overall capacity of Ca(2+) dependent proteolysis is likely to increase in differentiating myoblasts and should be contributed by m-calpain. Filamin (250 kDa), that is known to facilitate actin microfilament assembly and interfere with actin-myosin filament formation, was found to be cleaved in cultured myoblasts to 240 kDa products. This filamin-cleavage occurred in a manner similar to the in vitro cleavage of the cytoskeletal protein by the purified m-calpain. Moreover, the filamin cleavage was most evident at the period of the cell fusion. Thus, it seems likely that the in vivo cleavage of filamin is mediated by m-calpain. These results suggest that m-calpain may play an important role in cytoskeletal reorganization that is requisite for myoblast fusion. PMID- 8435440 TI - Direct gastrin action on isolated rat parietal cells induces morphological transformations. AB - In isolated rat parietal cells, a potentiating effect by gastrin of the stimulatory action of histamine and dibutyryl-cAMP (DBcAMP) on aminopyrine accumulation, an index of the acid formed and trapped by the cells, was recently reported by us (1991, Am. J. Physiol. 261, G621-G627). In the present study, this mechanism of action of gastrin was further investigated. Enriched parietal cells (approximately 65% parietal cells) were incubated under different conditions and processed for electron microscopy. Morphometric analysis of the micrographs revealed that pentagastrin (100 nM) was as efficient as histamine (100 microM) in inducing the formation of vacuolar/canalicular spaces in the parietal cells. In the presence of the histamine H2-receptor antagonist ranitidine, histamine was ineffective but pentagastrin and gastrin-17 (G17) maintained their capacity to induce the morphological transformations. By stimulation with pentagastrin plus histamine, the vacuolar/canalicular volume was 2-fold higher than by stimulation separately with each one of the secretagogues. G-17 (100 nM) alone was ineffective but potentiated the maximal [14C]aminopyrine accumulation obtained with 100 microM histamine in mucosal cells (approximately 25-35% parietal cells). Ranitidine blocked both histamine-and histamine plus G-17-stimulated aminopyrine accumulation. G-17 potentiated also the stimulation by 1 mM dibutyryl-cyclic AMP but this was not inhibited by ranitidine. Pentagastrin (100 nM) increased the basal [14C]glucose oxidation in mucosal cells by 30%. This increase was not blocked by ranitidine which, however, abolished the histamine-stimulated glucose oxidation. Incubation of the cells with pentagastrin plus histamine resulted in a glucose oxidation which equaled the sum of the values obtained by each one of the agents. These results indicate that gastrin, acting directly on the parietal cells, potentiates the action of histamine on aminopyrine accumulation by increasing the vacuolar/canalicular spaces, a process that is reflected in the metabolic activity of the cells. Thus a major effect of gastrin at the parietal cell level appears to be the induction of a morphology which is characteristic of stimulated cells rather than a direct activation of ion-transport mechanisms. PMID- 8435441 TI - Responses to heat shock of alpha B crystallin and HSP28 in U373 MG human glioma cells. AB - Responses to heat shock of alpha B crystallin and small heat-shock protein HSP28, which are expressed at considerable levels in human astroglioma U373 MG cells (2 4 micrograms of each per mg soluble protein in confluent cultures), were analysed quantitatively by specific immunoassays. Concentrations of alpha B crystallin and HSP28 in soluble extracts of U373 MG cells decreased to about 50% of original values, with an increase in the insoluble fraction, during heat treatment for 15 min at 45 degrees C. The concentrations of alpha B crystallin and HSP28 increased gradually upon return to 37 degrees C, reaching and then exceeding the control levels within 5 h and 10 h, respectively, after heat shock. During centrifugation on sucrose density gradients both alpha B crystallin and HSP28 in extracts from untreated and heat-treated cells sedimented at the same position, which corresponded to a molecular mass of > 540 kDa. This result suggests that the sizes of aggregates of the two proteins in the cytoplasm are not affected by heat shock. Both alpha B crystallin and HSP28 in an extract of U373 MG cells were trapped on and coeluted from an affinity column prepared with antibodies against alpha B crystallin. These results suggest that the two proteins are also associated in U373 MG cells. PMID- 8435442 TI - Intracellular calcium mobilization in rat platelets is adversely affected by copper deficiency. AB - The influence of copper deficiency on the mobilization of Ca2+ from intracellular stores following ionomycin treatment or thrombin activation of rat platelets was examined using the fluorescent indicator, fura-2, to measure changes in cytosolic Ca2+ concentration ([Ca2+]i). Platelets, obtained from copper-deficient and control rats and loaded with fura-2, were suspended in medium containing 1 mM EGTA and no added Ca2+. The size of the internal Ca2+ pools in the suspended platelets was estimated from the rise in [Ca2+]i following maximal discharge of stored Ca2+ by treatment with 1 microM ionomycin. Peak [Ca2+]i following ionomycin treatment was lower in platelets from copper-deficient rats compared to control rats (148 +/- 27 nM vs. 188 +/- 17 nM), suggesting that the size of the Ca2+ storage pools was decreased by copper deficiency. Furthermore, once internal Ca2+ stores were discharged by ionomycin, [Ca2+]i remained elevated in platelets from copper-deficient rats, but decreased in control rats. These data indicate that copper deficiency may inhibit the efflux of Ca2+ from platelets after its release from internal stores by ionomycin treatment. In platelets from copper deficient and control rats, stimulation with 0.1 U/ml thrombin led to rapid rise followed by a slow decay in [Ca2+]i. However, peak [Ca2+]i was lower in platelets from copper-deficient rats than in control rats (94 +/- 19 nM vs. 131 +/- 16 nM). These findings imply that by reducing the amount of Ca2+ available for release from intracellular stores, copper deficiency also reduces [Ca2+]i following thrombin activation in the absence of external Ca2+. PMID- 8435443 TI - Effect of palmitate concentration on the relative contributions of the beta oxidation pathway and citric acid cycle to total O2 consumption of isolated rat hepatocytes. AB - The relative contributions of beta-oxidation and citric acid cycle activity to total O2 consumption during fatty acid oxidation were examined in isolated hepatocytes. When hepatocytes were incubated with palmitate alone, a rise in fatty acid concentration induced an increase in O2 uptake that reflected a large stimulation of beta-oxidation and an accompanying smaller inhibition of citric acid cycle oxidation. In the presence of lactate, successive increments in palmitate concentration over the range from 0 to 1.0 mM stimulated glucose synthesis and brought about a concomitant incremental stimulation of both beta oxidation and citric acid cycle flux. However, above 1.5 mM palmitate, additional increments in fatty acid concentration depressed gluconeogenesis and citric acid cycle activity but induced a further stimulation of beta-oxidation. These findings demonstrate that, during fatty acid oxidation, the rate of citric acid cycle turnover is more closely linked to the rate of glucose synthesis than is the rate of beta-oxidation. This may be relevant to observations that the stimulation of hepatic O2 consumption, induced by fatty acid oxidation, is much greater than can be explained in terms of the ATP-demand arising from exposure of hepatocytes to fatty acid. PMID- 8435444 TI - Increased accumulation of drugs in a multidrug resistant cell line by alteration of membrane biophysical properties. AB - Growth of CHRC5 multidrug resistant cells in media enriched in a saturated C-17 fatty acid, heptadecanoic acid, resulted in these cells accumulating vinblastine at a rate and to an extent comparable to that of the parental cell line AB1. The fatty acid-enriched growth media had no effect on the ability of AB1 cells to take up vinblastine. The action of amphiphiles on the uptake of rhodamine dyes by CHRC5 cells was compared with the increased dye accumulation affected by verapamil. Membrane rigidifying agents, such as the saturated fatty acid stearic acid, or the cholesterol derivatives, cholesteryl hemisuccinate and cholesteryl phosphorylcholine, as well as a membrane fluidizing unsaturated fatty acid, linoleic acid, could significantly increase dye uptake, although not as well as verapamil. These results taken in conjunction with other reports in the literature, demonstrate that multidrug resistance is sensitive to alterations of membrane properties. They suggest that perturbation of the membrane to either increased or to decreased membrane fluidity can lower the level of resistance. PMID- 8435445 TI - Aldose reductase is involved in long-term adaptation of EUE cells to hyperosmotic stress. AB - Aldose reductase has been shown to be expressed in large amount by human embryonic epithelial cells (EUE) in response to osmotic stress. This conclusion is the result of studies undertaken following the purification to homogeneity of two forms of a 35-kDa protein overexpressed in EUE cells grown in hypertonic saline culture medium as compared to EUE cells grown in isoosmotic medium. Amino acid composition, molecular weight and partial internal amino-acid sequence showed that the above proteins are two different forms of aldose reductase. These findings were confirmed by the observation that aldose reductase activity increased about 150-fold in adapted cells and returned to basal levels in de adapted cells. PMID- 8435446 TI - Sodium nitroprusside inhibits glucose-induced insulin release by activating ATP sensitive K+ channels. AB - Sodium nitroprusside (SNP) has been reported to be a potent stimulator of cGMP formation in different tissues, including pancreatic islets. The present study aimed at comparing the effects of sodium nitroprusside and dibutyryl cGMP on 86Rb outflow, 45Ca outflow, short-term 45Ca uptake, cytosolic Ca2+ concentration and insulin release from rat pancreatic islet cells. The data indicate that cGMP potentiates whilst SNP inhibits the glucose-induced insulin release. This inhibitory effect appears to be mediated by the activation of ATP-sensitive K+ channels leading to a decrease in Ca2+ influx and subsequent reduction in cytosolic free Ca2+ concentration. Whatever the exact mechanism(s) underlying the capacity of sodium nitroprusside to enhance the K+ permeability of the B-cell membrane, the drug appears to be an inadequate pharmacological tool to characterize the involvement of cGMP in the insulin secretory process. The experimental results also suggest that cGMP potentiates glucose-induced insulin release without affecting ionic movements. PMID- 8435447 TI - The synthesis of IL-1 receptor antagonist (IL-1ra) by synovial fibroblasts is markedly increased by the cytokines TNF-alpha and IL-1. AB - The regulation of inhibitors which block the action of IL-1 has significant implications in the control of inflammation. Different modulators of cellular metabolism were studied for their effect on the synthesis of IL-1 receptor antagonist (IL-1ra). Among the different growth factors and cytokines studied, only the inflammatory mediators IL-1 and TNF-alpha and one growth factor, PDGF BB, were found to significantly increase, in an additive manner, the synthesis and secretion of IL-1ra. PMID- 8435448 TI - Phosphorylation of the porcine skeletal and cardiac muscle sarcoplasmic reticulum ryanodine receptor. AB - Porcine skeletal and cardiac muscle sarcoplasmic reticulum (SR) vesicle fractions enriched in the ryanodine receptor were phosphorylated in the presence of [gamma 32P]MgATP and either exogenous cAMP-dependent protein kinase (cAMP-PK), or Ca2+ plus calmodulin. Phosphorylation of the cardiac muscle ryanodine receptor in the presence of either cAMP-PK or calmodulin (6.4 and 10.6 pmol Pi/mg SR respectively) was approximately equal to or twice the [3H]ryanodine binding activity of this preparation (5.2 pmol/mg). Furthermore, cardiac muscle ryanodine receptor Pi incorporation catalyzed by cAMP-PK and calmodulin was approximately additive. In skeletal muscle SR, however, the level of cAMP-PK or calmodulin catalyzed phosphorylation of the intact ryanodine receptor (0.2 or 2.9 pmol Pi/mg SR, respectively) was much less than the [3H]ryanodine binding activity of this fraction (11.6 pmol/mg). Furthermore, Pi incorporation into the intact skeletal muscle ryanodine receptor was 3-8-fold less than that incorporated into a component of slightly lower M(r). Although this latter component comigrated with an immunoreactive fragment of the ryanodine receptor on polyacrylamide gels, it did not appear to be derived from the ryanodine receptor. We conclude that the significant phosphorylation of the cardiac muscle SR ryanodine receptor indicates a likely physiological role for protein kinase-mediated regulation of this Ca(2+) channel. In contrast, the minimal phosphorylation of the skeletal muscle SR ryanodine receptor indicates that such a role of protein kinases is unlikely in this tissue. PMID- 8435449 TI - Characteristics of arachidonic-acid-mediated brain protein kinase C activation: evidence for concentration-dependent heterogeneity. AB - Arachidonic acid (AA) activates brain protein kinase C (PKC) in a specific manner, and which differs from that of diacylglycerol (DG)-mediated PKC activation in cofactor Ca2+ and phosphatidylserine (PtdSer) requirements. We presently report that characteristics of AA-mediated activation are heterogenous, and are dependent upon the concentrations of AA. Highly sensitive PKC activation (HS) occurring at concentrations of 20 microM AA can be distinguished from less sensitive PKC activation (LS) requiring concentrations of at least 160 microM AA, on the basis of the effects of phorbol ester TPA or DG, phosphatidylcholine (PtdCho) and sodium deoxycholate (DOC). TPA, like DG suppressed the HS reaction whereas it enhanced the LS reaction. PtdCho, a phospholipid which does not affect DG-mediated activation, also prevented the HS reaction without affecting the LS reaction. This latter was inhibited at 100 microM DOC, a concentration which slightly stimulated the HS reaction. The substrate specificity was also different in the two reactions: the preferential substrate for PKC in HS was histone type VII-S, while it was histone type V-S in LS. Both reactions were similarly affected by PtdSer. In 0.1 mM CaCl2, PtdSer stimulated AA-mediated activation without evoking additive responses while this phospholipid prevented this activation in 0.5 mM EGTA, suggesting that AA and PtdSer bind PKC on the same or related sites. Together these results provide evidence for the existence of different modes of AA-mediated PKC activation with unique characteristics which presumably involve two different binding sites for AA on the same molecule and/or different PKC isoforms. PMID- 8435450 TI - Auditory evoked fields covary with perceptual grouping. AB - Abrupt acoustic events evoke a transient magnetic response (N100m) at the supratemporal plane. Such responses decrease in amplitude as the interval between successive stimuli decreases to about 1 s. However, when pairs of stimuli are separated by still smaller intervals the second stimulus evokes a larger response than the first. This enhancement depends on the duration of the pause between the offset of the first stimulus and onset of the second. The range over which enhancement of N100m is observed agrees quite well with the range over which subjects experience perceptual grouping of the two stimuli with loudness enhancement of the second. Recordings from multi-channel SQUID gradiometers show that the effect involves not only a change in source strength but also a change in source location within supratemporal cortex. The results suggest that inhibition induced by onset of the first stimulus may be disinhibited by its offset. Physiological and psychological implications are discussed. PMID- 8435451 TI - Vascular disease risk factors, urinary free cortisol, and health histories in older adults: shyness and gender interactions. AB - We studied relationships between shyness and health during a health screening survey of older adults (ages 50-88) living in an active retirement community in the southwestern United States (n = 232). As in previous studies of infants, older individuals with hay fever, insomnia and constipation were more shy than those without these problems. Shy persons overall showed higher sitting systolic blood pressure and a larger fall in orthostatic systolic blood pressure on standing; shy men had a greater prevalence of hypertension histories than did low shy men. Shy subjects of both sexes had lower HDL cholesterol and higher triglycerides than did low-shy subjects; shy women tended to have higher LDL cholesterol than did low-shy women. In contrast with findings of elevated salivary cortisol in extremely inhibited children of both sexes, only shy women had higher 24 h urinary free cortisol excretion than did low-shy women; men showed the opposite pattern, possibly related to suppression of aggression. Shy men also tended to report a higher prevalence of thyroid disease history than did low-shy men (20% versus 6%). Notably, autoimmune thyroiditis has previously been linked with panic and depression, disorders which in turn have been associated with shyness. Taken together with previous work in shy children and their families, the data raise the possibility of (a) increased risk for arteriosclerotic vascular disease; and (b) increased risk of adrenal- and/or thyroid-related diseases in certain shy older adults. PMID- 8435452 TI - Memory and attention dysfunctions in story recall in schizophrenia: evidence of a possible frontal malfunctioning. AB - Story recall deficits in schizophrenia have been related to some deficit in interhemispheric transfer of information, suggestive of a collosal pathology or, alternatively, to malfunctioning in attention and mnesic systems. The present investigation, performed on 61 DSM-IIIR schizophrenic inpatients and 40 age-and education-matched, normal controls demonstrates that story recall deficit is dependent on the length and complexity of the stories. This finding might implicate a critical role for the attention and mnesic functions in determining story recall performances. Both functions have an anatomo-functional substrate in neural circuits involving the frontal lobe, which also plays a critical role in determining the level of the conceptualization and abstraction capacities. PMID- 8435453 TI - Graphical and statistical techniques for cardiac cycle time (phase) dependent changes in interbeat interval: problems with the Jennings et al. (1991) proposals. AB - Two apparently new effects in human cardiac responding, "primary bradycardia" and "vagal inhibition", were first described by the Laceys. These effects have been considered by some researchers to reflect differential cardiac innervation, analogous to similar effects observed in animal preparations with direct vagal stimulation. However, it has been argued that such effects arise merely from the data-analytic techniques introduced by the Laceys, and hence are not genuine cardiac cycle effects. Jennings, van der Molen, Somsen and Ridderinkhoff (Psychophysiology, 28 (1991) 596-606) recently proposed a plotting technique and statistical procedure in an attempt to resolve this issue. The present paper demonstrates that the plotting technique fails to achieve their stated aim, since it identifies data from identical cardiac responses as showing cardiac-cycle effects. In addition, the statistical procedure is shown to be reducible to a trivial test of response occurrence. The implication of these demonstrations, in the context of other work, is that this area of investigation has reached a dead end. PMID- 8435454 TI - Bone healing after bone marrow stromal cell transplantation to the bone defect. AB - In experimental studies on rabbits, osteogenic properties of stromal cells were confirmed after in vitro growth for 7 and 14 d. The cell suspension was percutaneously transplanted into a surgically produced bone defect in the rabbit's radius. The bone scar produced was X-rayed, and histologically and mineralogically examined after 10, 20 and 40 d follow-ups. Differences in the bone defect healing process (the healing rate and the type of bone tissue produced) were shown between the experimental and the control foreleg. Within the experimental foreleg, healing was considerably accelerated with compact bone formation on a membranous matrix, whilst in the control foreleg, a coarse, fibrous woven bone on a cartilaginous matrix was dominant. PMID- 8435455 TI - Haemocompatibility of Ti6A14V alloy. AB - Ti6A14V alloy has been mainly used as a biomaterial in the orthopaedic field. The present study describes the surface state of the Ti6A14V material and evaluates its in vitro haemocompatibility in terms of protein adsorption, platelet retention and haemolysis. The behaviour of the Ti6A14V alloy towards albumin and fibrinogen was compared to that of a reference medical-grade elastomer. The platelet retention test gave better results than those achieved with the elastomer. The haemolysis percentage of the alloy was almost zero. These results indicate that the Ti6A14V alloy is well tolerated by blood. PMID- 8435456 TI - Stiffness variability and stress-dependent elastic response of synthetic fibre reinforced composites for biomedical applications. AB - A major design requirement of biomaterial prostheses is to match their elastic properties with those of the natural host tissue. Composite materials address this requirement because their elastic properties can be altered accurately through composition and directionality parameters, and they can be designed to match closely the elastic properties of the biological tissues, in isocompliance, modulus gradient and anisotropy. This adds to a range of advantages of synthetic composite materials with respect to potential biomedical applications, which draw on their heterogeneity and anisotropy. This paper focuses on the elastic properties of synthetic fibre-reinforced composite materials that pertain to biomedical applications, and demonstrates the range of stiffnesses obtainable through selection of constituents and by choice of angle of reinforcement. PMID- 8435457 TI - Effect of saline solution on creep fracture of Delrin. AB - Delrin as an implant material has been widely used for more than 26 yr. To determine the combined effect of stress and body fluid environment on the stress limits of polyacetal, the creep rupture behaviour of Delrin in saline (0.9% NaCl) solution at 37 degrees C was studied. A creep rupture model was used to predict the upper (immediate fracture) and lower (no fracture) stress limits and the elastic ratio (Ee/Ea). The results showed that saline solution adversely affected the lower stress limit and Ee/Ea, but not the upper stress limit. Brittle fracture with a strain < 5% occurred for most specimens. This may explain why Delrin can fail prematurely in orthopaedic implants. Design stresses using Delrin as implant material have to be reduced by four times to 5 MPa and the strain limited to 5% as opposed to 20%, as previously believed. The increase in Ee/Ea also implied that the microdeformation mechanism is changed. The presence of surface cracks indicated that Delrin is susceptible to environmental stress cracking in saline solution. PMID- 8435458 TI - States in adherent platelet morphology and the processing of adsorbed protein on biomaterials. AB - This study evaluates the range of adherent platelet morphologies and their relationship to preadsorbed protein. Fluorescently labelled protein was used so changes in its distribution could be followed along with morphological states assessed with modulation-contrast microscopy. Our particular concern was with the quantitative relationship between the platelet and the fluorescent image. The findings from this study continue to support the idea that platelets do interact with adsorbed protein so that protein redistribution occurs and that thrombin accelerates this. Evidence is also presented to support platelet shrinkage, membrane vesicle formation and destruction as a result of thrombin. The shrinking of adherent platelets causes areas free of pre-adsorbed protein to be exposed. This process will be important determining the nature of the substrate available to cells contacting surfaces along with other adsorbed protein-related processes, e.g. reversible adsorption and post-adsorptive transitions. PMID- 8435459 TI - ESCA surface characterization of four IUPAC reference polymers. AB - Four reference polymers studied by the International Union of Pure and Applied Chemistry working party on interactions of polymers with living systems were characterized by electron spectroscopy for chemical analysis. The surface of a polyethylene specimen was found to consist of only hydrocarbon (-CH2-) groups, as expected. Similarly, the surface of a poly(dimethyl siloxane) was found to be in close agreement with the expected stoichiometry of this polymer. The surface of the PVC sample showed a high surface concentration of hydrocarbon-rich plasticizer. Also, Si, O and Zn were detected. Cellulose coil specimens were heavily silicone contaminated. A 24 h rinse of this material in water reduced the Si level to 5%, and produced a surface spectrum closer to that expected for cellulose. PMID- 8435460 TI - Preliminary report on cell culture on a thermally reversible copolymer. AB - Anchorage-dependent cells (NRK 49F) were grown at 37 degrees C in serum containing medium on glass coated with a N-isopropyl acrylamide/N-t-butyl acrylamide copolymer (NIPAaM/NTBAM) with a lower critical solution temperature (LCST) of 8 degrees C. After incubating the dishes and adherent cells at 4 degrees C for 1 h, the cells had started to detach in 'sheets', without the use of trypsin; by 2 h the cells had fully detached and formed aggregates. We presume that at 4 degrees C, below the LCST of the coating, the polymer swelled and eventually dissolved, leaving the cells unattached to the solid substrate. We speculate that the 'sheet' morphology of the detaching cells implies that the extracellular matrix produced by the cells during culture was left intact, which may then alter the nature of their subsequent behaviour. The polymer was not optimum for cell attachment and optimization would be needed to realize the potential of this novel mode of cell culture and recovery. PMID- 8435461 TI - Influence of indomethacin on the regeneration of cortical bone within titanium implants in rabbits. AB - The influence of indomethacin on cortical bone regeneration was studied in bone harvest chambers made of commercially pure titanium and inserted in rabbit tibia. Newly formed bone was harvested in situ every 3 wk for 33 wk. Indomethacin (1 mg/kg body weight) was given daily as subcutaneous injections for two periods, followed by two control periods with no drug administration and the same schedule was followed for indomethacin at a dose of 4 mg/kg body weight. These indomethacin dosages did not statistically influence the cortical bone regeneration. PMID- 8435462 TI - Poly(ethylene oxide) (PEO) and different molecular weight PEO blends monolithic devices for drug release. AB - An interpretation of the drug release from monolithic water-swellable and soluble polymer tablets is presented. A convenient parameter, alpha, which compares the drug-diffusive conductance in the gel layer with the swelling and dissolving characteristics of the unpenetrated polymer was used to describe the release behaviour of beta-hydroxyethyl-theophylline (etofylline) from compression-moulded tablets of hydrophilic pure semicrystalline poly(ethylene oxides) of mol wt 600,000 and 4,000,000 and of two blends of the two molecular weights of poly(ethylene oxides). The water swelling and dissolution characteristics of two polymers and two blends were analysed, monitoring the thickness increase of the surface-dissolving layer and the rates of water swelling and penetration in the tablets. The drug diffusivities in the water-penetrated polymer gels were measured by carrying out permeation tests. Finally, drug release tests were performed to investigate the release kinetics of the different systems in an aqueous environment at 37 degrees C. The drug release from the high molecular weight poly(ethylene oxide) is principally related to the material swelling rather than polymer dissolution, leading to a progressive decrease of the drug's diffusive conductance in the growing swollen layer, and hence to a non-constant release induced by the prevailing diffusive control. Conversely, drug release from the low molecular weight poly(ethylene oxide) is strictly related to the polymer dissolution mechanism. The achievement of stationary conditions, in which the rate of swelling equals the rate of dissolution, ensures a constant release rate, even in the case of very low drug-diffusive conductance in the external gel layer. Intermediate behaviours were detected in the case of the two blends. PMID- 8435463 TI - The therapy of oral lichen planus. AB - Oral lichen planus is a chronic mucocutaneous disease that is relatively common. Although many patients are asymptomatic and require no therapy, those who exhibit atrophic and erosive lesions are often a challenge to treat. All therapies are palliative, and none is effective universally. Currently employed treatment modalities include corticosteroids administered topically, intralesionally, or systemically. Alternative therapies include topical and systemic retinoids, griseofulvin, Cyclosporine, and surgery. Other medical treatments and experimental modalities, including mouth PUVA, have been reported to be effective. Controversy concerning the efficacy of all these treatments suggests that oral lichen planus is a heterogeneous disorder. Eliminating lichenoid drug eruptions, candidiasis, trauma, contact mucositis, and emotional stress may play a role in the management of these patients. This article is a review of the many treatments and measures that have been employed in the management of patients with oral lichen planus. PMID- 8435464 TI - Virulence factors of mutans streptococci: role of molecular genetics. AB - Biochemical approaches were utilized initially to identify the virulence factors of the mutans streptococci (primarily Streptococcus mutans and S. sobrinu). Traditional mutant analysis of these organisms further suggested the important role of several of these factors in cariogenicity. However, because these mutations were not clearly defined, the utilization of cloned genes was necessary to verify their significance. The introduction of molecular genetic approaches for characterizing these factors has led not only to a clearer understanding of the role of these virulence factors in cariogenicity but has also suggested some novel approaches for reducing further the incidence of dental caries. PMID- 8435465 TI - Nonsteroidal antiinflammatory drugs as inhibitors of periodontal disease progression. AB - Recent interest in the control and modulation of periodontal disease has focused on the potential benefits of blocking the host response mechanisms involved in the progression of the disease. In addition to recent advances in the identification and control of etiologic bacteria, investigators have indicated promising results using nonsteroidal antiinflammatory drugs (NSAIDs) as inhibitors of the inflammatory destruction in periodontal disease. This article examines research efforts over the last 20 years describing the role of prostaglandins in periodontal disease and the effect of NSAIDs on the progression of gingival inflammation and alveolar bone loss. PMID- 8435466 TI - Matrix metalloproteinases: a review. AB - Matrix metalloproteinases (MMPs) are a family of nine or more highly homologous Zn(++)-endopeptidases that collectively cleave most if not all of the constituents of the extracellular matrix. The present review discusses in detail the primary structures and the overlapping yet distinct substrate specificities of MMPs as well as the mode of activation of the unique MMP precursors. The regulation of MMP activity at the transcriptional level and at the extracellular level (precursor activation, inhibition of activated, mature enzymes) is also discussed. A final segment of the review details the current knowledge of the involvement of MMP in specific developmental or pathological conditions, including human periodontal diseases. PMID- 8435467 TI - Effect of experimental hypertension on phosphoinositide hydrolysis and proto oncogene expression in cardiovascular tissues. AB - Products of inositol lipid hydrolysis and levels of c-myc, c-fos and H-ras mRNAs were measured in rat left ventricle and vascular tissues 72 h and 9 days after the induction of aortic coarctation in order to examine inositol phosphate and proto-oncogene signals during the development of pressure-related cardiac and vascular structural changes. There was a significant increase in left ventricular and proximal aortic mass at both time points but no change in mesenteric resistance artery morphology in rats with coarctation. At 72 h there was a significant increase in c-myc, c-fos and H-ras mRNAs in the left ventricle of rats with coarctation, and this was accompanied by increased levels of inositol (1,4,5)-trisphosphate. Similar results were obtained in the proximal but not the distal aorta. In resistance arteries inositol phosphate production and proto oncogene mRNA expression were unchanged. The results indicate that at 72 h aortic coarctation induced structural thickening in the left ventricle and proximal aorta and was associated with increased inositol phosphate production and stimulation of specific proto-oncogene mRNAs. By 9 days following surgery much of the structural change in these tissues was completed, and these raised cellular signals were no longer observed. The results suggest that both increased inositol lipid hydrolysis and a rise in the expression of these proto-oncogenes are important processes in the development of vascular hypertrophy seen in this model of hypertension. PMID- 8435469 TI - Dose-related changes in the mechanical properties of the carotid artery in WKY rats and SHR following relaxation of arterial smooth muscle. AB - Acute converting enzyme inhibition relaxes arterial smooth muscle and increases arterial compliance in several models of animal and human hypertension. However, it is unknown whether the doses needed for the relaxation of large arteries are similar to those inducing arteriolar relaxation and blood pressure (BP) decrease. To answer this question, we used a previously described model of the in situ carotid artery to determine the pressure-volume relationship over a range of transmural pressures from 25 to 200 mm Hg in normotensive rats (WKY) and spontaneously hypertensive rats (SHR). The pressure-volume relation was determined after an acute single oral administration of either a placebo or the converting enzyme inhibitor quinapril given at two different doses (0.3 or 3 mg/kg). At the end of each experiment, the total relaxation of arterial smooth muscle was achieved after a local administration of potassium cyanide (KCN). In the WKY placebo group, from 25 to 100-125 mm Hg transmural pressure, carotid compliance increased and reached a maximum value at 100-125 mm Hg (i.e. close to the operating range of systemic mean BP of the animals), and decreased thereafter. In the SHR placebo group, carotid compliance was significantly lower than in the WKY placebo group for transmural pressure up to 125 mm Hg, and thereafter was equal or even higher; the maximum value of compliance was reached at 125-150 mm Hg transmural pressure, i.e. substantially less than the operating range of the systemic mean BP of the SHR placebo (180 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8435468 TI - Vascular pharmacology of ATP-sensitive K+ channels: interactions between glyburide and K+ channel openers. AB - This study in isolated rabbit superior artery (RMA) investigated the interactions between glyburide, a known blocker of vascular ATP-sensitive K+ channels (KATP), and several chemically diverse potassium channel openers (PCOs): minoxidil sulfate (MNXS; 5 microM), pinacidil (1 microM), cromakalim (0.5 microM) and RP 49356 (1 microM; a PCO from Rhone Poulenc). Relaxation time courses for these PCOs were obtained in norepinephrine (NE; 5 microM)-precontracted RMA, and the concentrations of PCOs found to be equipotent to each other in terms of the degree of maximum relaxation (about 80%) and the time course of relaxation (within 15 min) were chosen for further study. This was taken as a functional indicator of a similar degree as well as similar kinetics of K+ channel opening by these PCOs. Pretreatment with glyburide (10-500 nM) produced a dose-dependent inhibition of the PCO relaxation time course. The glyburide IC50s against pinacidil, MNXS and RP-49356 were statistically similar and ranged from 72-79 nM. The glyburide IC50 against cromakalim was a modest 2-fold higher, at 148 nM. In contrast, pretreatment with charybdotoxin (200 nM) produced no significant inhibition of the maximum relaxation produced by these PCOs. Furthermore, glipizide, a sulfonylurea that is 10- to 25-fold less potent than glyburide for insulin secretion, was found to be 20- to 30-fold less potent than glyburide as a vascular KATP antagonist. These data suggest a mechanistic model in which these structurally diverse PCOs share a common critical step in the sequence of events leading to the KATP opening, and that glyburide interferes with this common critical step to produce a similar type of blockade against all four PCOs. Interaction studies with glyburide and pinacidil demonstrated 15 min to be the optimal pretreatment time for glyburide to produce maximal inhibition. Glyburide also reversed existing pinacidil relaxation regardless of the degree of pre existing relaxation. These data suggest that glyburide is able to produce its blockade regardless of the state of K+ channel activation. Studies on the effect of pH (6.4 vs. 7.3) showed that at acidic pH, pinacidil became less effective and the effectiveness of glyburide was significantly enhanced, whereas the actions of D600 remained unchanged. These data suggest the effects of both openers and blockers of the KATP are strongly pH dependent. PMID- 8435470 TI - Histamine responsiveness of the various vascular beds of facial and nasal tissues in the dog. AB - The effects of the close arterial infusion of histamine upon the microcirculation of facial and nasal tissues were examined in dogs. Blood flow through arteriovenous anastomoses (AVA flow), capillaries (CAP flow) and collaterals (COL flow) were determined by electromagnetic flowmetry and the tracer-microsphere technique following an infusion of histamine at doses ranging from 0.5 to 50 nmol/min. Low doses of histamine (0.5-5.0 nmol/min) resulted in an increase in blood flow through the ipsilateral internal maxillary artery (IMA), which could be mainly attributed to a significant elevation of the CAP flow. A concomitant marked increase in AVA flow was observed only after the administration of higher doses (20-50 nmol/min). Significant changes in systemic blood pressure, heart rate and cardiac output occurred only after the infusion of histamine at doses of 20 and 50 nmol/min. Significant increases in the CAP flow of tissues with relatively low perfusion were observed after the infusion of histamine at lower doses. The CAP flow of structures which play an essential role in conditioning the inspired air and exhibit high perfusion rates under control conditions exhibited significant increases only after the administration of higher doses. The present experiments provide direct evidence for a dose-dependent vasodilatory effect of histamine on different microcirculatory compartments of cutaneous and mucosal vascular beds supplied by the IMA in the dog. The results indicate that at low blood histamine levels, an increase in CAP flow predominates, and at higher doses, both elevated CAP flow and elevated AVA flow contribute to the vasodilatory response to histamine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8435471 TI - Cardioplegia alters porcine coronary endothelial cell growth and responses to aggregating platelets. AB - Experiments were designed to determine the viability of endothelial cells and their responses to products released by aggregating platelets following single flush perfusion of the coronary arteries with cardioplegic solutions used for cardiac transplantation. Porcine coronary arteries were perfused with crystalloid (Plegisol) or blood cardioplegic solutions; nonperfused hearts placed in 0.9% saline were used as controls. Immediately following perfusion and after 5-hour storage of the hearts in the same cardioplegic solution, rings were cut from the right coronary arteries and suspended in organ chambers for the measurement of isometric force. In some rings the endothelium was removed deliberately. The left circumflex coronary arteries were flushed with collagenase and the harvested endothelial cells were plated for cell culture. Left anterior descending coronary arteries were perfusion fixed with glutaraldehyde for scanning electron microscopy. In the organ chamber experiments, aggregating platelets and adenosine diphosphate caused relaxations in rings with endothelium. These relaxations were reduced immediately following crystalloid cardioplegia and were restored following 5-hour storage. Serotonin caused contractions in all rings. Rings without endothelium were more sensitive than rings with endothelium to the amine; this difference was augmented following 5-hour storage of the heart. Significantly fewer foci of endothelial cells grew in culture following 5-hour storage of the hearts in crystalloid cardioplegic solution compared to control (p < 0.05). There were no anatomical differences identified among groups by scanning electron microscopy. These results suggest that crystalloid cardioplegia alters the responses of coronary arteries to substances released by aggregating platelets and reduces the ability of endothelial cells to replicate. Such changes may contribute to altered vascular resistance following reperfusion of transplanted hearts and potentially to later structural changes in the coronary arteries. PMID- 8435472 TI - Role of cytochrome P-450 in elevating renal vascular tone in spontaneously hypertensive rats. AB - The contribution of cytochrome P-450 metabolites of arachidonic acid in elevating vascular tone in the kidneys of adult spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats was examined using a juxtamedullary nephron microvascular preparation perfused in vitro with a physiological salt solution containing 5% albumin. At 80 mm Hg, the basal internal diameters of arcuate and interlobular arteries and proximal and distal afferent arterioles of the SHR averaged 341 +/- 15.81 +/- 5.24 +/- 0.5 and 19 +/- 0.3 micron, respectively. These diameters were 5-29% smaller (p < 0.05) than those measured in corresponding vessels in WKY rats. Addition of the P-450 inhibitors, ketoconazole (100 microM) or 17 octadecynoic acid (17-ODYA, 20 microM), to the perfusate and bath increased the diameters of the preglomerular vasculature of the SHR by 6-29%, but by only 3-13% in WKY rats and reduced significantly the differences in pressure-diameter relations between the two groups. The rate of formation of 20 hydroxyeicosatetraenoic acid (20-HETE) by renal cortical microsomes was similar in SHR and WKY rats. However, the production of epoxyeicosatrienoic acids (EETs) by cortical microsomes was 87% lower and dihydroxyeicosatrienoic acids (DHETs) 70% higher in the SHR than WKY rats. Ketoconazole (100 microM) reduced the formation of 20-HETE by 80%, and EETs and DHETs production by more than 98% in SHR and WKY rats. 17-ODYA (20 microM) reduced the formation of 20-HETE, EETs and DHETs by more than 98% in both groups. These results suggest that cytochrome P 450 metabolites of arachidonic acid contribute to the elevated renal vascular tone in adult SHR. This may be due to an enhanced vascular responsiveness to vasoconstrictor P-450 metabolites in SHR or an elevated local production of vasoconstrictor eicosanoids in the renal vasculature of SHR rather than in renal cortical tissue. PMID- 8435473 TI - The role of cell adhesion molecules in cancer invasion and metastasis. AB - Invasion and metastasis of tumor cells is the primary cause for the fatal outcome of cancer diseases. A striking feature of metastatic cells is the considerable flexibility in their adhesive interactions with other cells or components of the extracellular matrix. This review will describe the involvement of specific cell adhesion receptors, extracellular matrix molecules, and cell dissociating cytokines in the metastatic cascade. We will particularly focus on disturbance of intercellular adhesion as a prerequisite for the release of invasive cells from carcinomas. We suggest that cell dissociation in these tumors is accomplished by loss of function or expression of the epithelial cell adhesion molecule E cadherin, and through the activity of cell motility factors, like scatter factor. PMID- 8435474 TI - Expression of the stromelysin-3 gene in fibroblastic cells of invasive carcinomas of the breast and other human tissues: a review. AB - Stromelysin-3 (ST3) is a putative new matrix metalloproteinase (MMP) which may play a role in the progression of human carcinomas, and exhibits unique structural and functional characteristics among the MMP family. The ST3 gene, which is generally not expressed at significant levels in benign breast tumors, has been found to be expressed in all invasive breast carcinomas tested so far. The gene is also expressed in some in situ breast carcinomas, which have a higher probability to become invasive. ST3 RNA and protein are specifically found in fibroblastic cells immediately surrounding the neoplastic cells, both in invasive and in situ breast carcinomas. The same expression pattern is observed in other types of human carcinomas, and the highest ST3 RNA levels are observed in tumors that exhibit high local invasiveness. The ST3 gene is also expressed in fibroblastic cells during the inflammatory phase of wound healing, which suggests that ST3 gene expression in stromal fibroblasts may be under the control of factors produced by inflammatory cells during wound healing, and by cancer cells during carcinoma progression. ST3 may thus represent a stroma-derived factor necessary for the progression of epithelial malignancies, and its manipulation may possibly be used to develop new anti-cancer agents. PMID- 8435475 TI - Urokinase (uPA) and its inhibitor PAI-1 are strong and independent prognostic factors in node-negative breast cancer. AB - Evidence has accumulated that invasion and metastasis in solid tumors require the action of tumor-associated proteases, which promote the dissolution of the surrounding tumor matrix and the basement membranes. The serine protease urokinase-type plasminogen activator (uPA), which is elevated in solid tumors, appears to play a key role in these processes. We used enzyme-linked immunoassays (ELISA) to test for uPA antigen and its inhibitor PAI-1 in tumor tissue extracts of 247 breast cancer patients who were enrolled in a prospective study. The relation of these data to known prognostic factors and to other variables such as DNA analysis and cathepsin D was studied. Disease-free and overall survival were analyzed according to Cox's proportional hazard model. The major new finding is that breast cancer patients with either high uPA (> 2.97 ng/mg protein) or high content of the uPA inhibitor PAI-1 (> 2.18 ng/mg protein) in their primary tumors have an increased risk of relapse and death. Multivariate analyses revealed uPA to be an independent and strong prognostic factor. The impact of uPA is as high as that of the lymph node status. In node-negative patients the impact of uPA is closely followed by that of PAI-1. Since uPA and PAI-1 are independent prognostic factors, the node-negative patients could be subdivided further by combining these two variables. In this refined analysis, patients whose primary tumors have lower levels of both antigens evidently have a very low risk of relapse (93% disease-free survival at three years) in contrast to patients with high uPA and high PAI-1 (55% disease-free survival at three years). The combination of uPA and PAI-1 in our group of patients with axillary node-negative breast cancer allows us to identify the 45 percent of patients having an increased risk of relapse. Consequently, more than half of the patients had less than a 10% probability of relapse and thus would possibly be candidates for being spared the necessity of adjuvant therapy. PMID- 8435476 TI - Type IV collagenases in invasive tumors. AB - The matrix metalloproteinases appear to be elevated in tumors with metastatic potential, and may well be involved in penetration of the basement membrane and degradation of extracellular proteins including type IV collagen. An imbalance between the 72 kDa and 92 kDa type IV collagenases and the associated tissue inhibitors of these metalloproteinases (TIMPs) may therefore have a role in the invasive phenotype. Cultured tumor cells with invasive potential secrete both type IV collagenases, though in tumors there is some evidence that the 72 kDa form at least may be produced by stromal cells at the invading tumor front rather than primarily by the tumor cells themselves, while the 92 kDa form may be synthesized in macrophages near the front. These collagenases are elevated in invasive as compared with in situ tumor components, but their specific roles and prognostic significance are not yet established. PMID- 8435477 TI - Evaluation of cathepsin D as a prognostic factor in breast cancer. AB - The biologic rationale for the importance of cathepsin D in breast cancer is a provocative one. Cathepsin D is both an estrogen inducible and a constitutively produced protease, which may also act directly as a peptide growth factor. Thus it may play a role in tumor invasiveness, and also in driving cell proliferation. Reported clinical studies are conflicting, with some studies showing cathepsin D levels to correlate with clinical outcome, and other studies finding prognostic significance only in selected subsets of patients, if any. Thus cathepsin D is a potentially important prognostic marker whose clinical application awaits further definition. PMID- 8435478 TI - Hormone resistance, invasiveness, and metastatic potential in breast cancer. AB - Critical phenotypic changes that occur during the progression of breast cancer include the loss of hormone-dependence, acquired resistance to systemic therapies, and increased metastatic potential. We have isolated a series of MCF-7 human breast cancer variants which exhibit hormone-independent growth, antiestrogen resistance, and increased metastatic potential. Analysis of the phenotypes of these variants strongly suggests that changes in the expression of specific genes may be critical to the generation of phenotypic diversity in the process of malignant progression in breast cancer. Epigenetic changes may contribute significantly to the generation of these phenotypic changes observed during breast cancer progression. Many of the characteristics of the progressed phenotypes appear to have arisen in response to appropriate selective pressures (growth in ovariectomized nude mice; growth in the presence of antiestrogens). These observations are consistent with the concept of clonal selection and expansion in the process of malignant progression. PMID- 8435481 TI - Lessons of Aedes aegypti control in Thailand. AB - The incidence of dengue haemorrhagic fever (DHF) in Thailand has increased cyclically since the first recognized outbreak in 1958. Without an effective vaccine against dengue, and considering the clinical difficulty of treating DHF cases, vector control is needed to prevent dengue transmission. Since the establishment of the WHO Aedes Research Unit in 1964, continued since 1973 as the WHO Collaborating Centre at the Department of Medical Research in Bangkok, much operational research has been carried out in Thailand on the bionomics and control of dengue vectors: Aedes aegypti and Ae. albopictus. This review shows that, as in most other countries, dengue vector control programmes in Thailand make little use of the procedures arising from research, nor have they reduced the upward trend of dengue or prevented DHF outbreaks. Implications of the reluctance to use results of operational research on vector control are considered and remedial suggestions made. PMID- 8435482 TI - Burrow patterns of the scorpion Heterometrus indus. PMID- 8435480 TI - The nude mouse as an in vivo model for human breast cancer invasion and metastasis. AB - Human breast cancer xenografts only rarely invade and metastasize in nude mice, and have therefore only had limited use as a model for studying mechanisms involved in breast cancer spreading. However, recent reports describe differences not only between various cell lines but also between strains of immune-deficient mice in terms of providing a model for studies of the invasive and metastatic capability of human breast cancer xenografts. Genetic labelling of human cancer cells with the lacZ gene is described as a specific and highly sensitive method for identification of micrometastases in such a model. PMID- 8435479 TI - Molecular and cellular analysis of basement membrane invasion by human breast cancer cells in Matrigel-based in vitro assays. AB - In vitro analyses of basement membrane invasiveness employing Matrigel (a murine tumor extract rich in basement membrane components) have been performed on human breast cancer model systems. Constitutive invasiveness of different human breast cancer (HBC) cell lines has been examined as well as regulation by steroid hormones, growth factors, and oncogenes. Carcinoma cells exhibiting a mesenchymal like phenotype (vimentin expression, lack of cell border associated uvomorulin) show dramatically increased motility, invasiveness, and metastatic potential in nude mice. These findings support the hypothesis that epithelial to mesenchymal transition (EMT)-like events may be instrumental in the metastatic progression of human breast cancer. The MCF-7 subline MCF-7ADR appears to have undergone such a transition. The importance of such a transition may be reflected in the emergence of vimentin expression as an indicator of poor prognosis in HBC. Matrix degradation and laminin recognition are highlighted as potential targets for antimetastatic therapy, and analyses of laminin attachment and the matrix metalloproteinase (MMP) family in HBC cell lines are summarized. Matrigel-based assays have proved useful in the study of the molecular mechanisms of basement membrane invasiveness, their regulation in HBC cells, and their potential as targets for antimetastatic therapy. PMID- 8435484 TI - Variation in density of cattle-visiting muscid flies between Danish inland pastures. AB - The density of cattle-visiting flies (Muscidae) and the load of black-flies (Simulium spp.) were estimated in twelve and eighteen inland pastures in Denmark in 1984 and 1985 respectively. No differences in the geographical distribution pattern of the predominant cattle-visiting Muscidae were recorded, whilst the relative abundance and density of the species and the total fly-load varied considerably between pastures. In most cases the mean loads of Haematobia irritans (L.) and Hydrotaea irritans (Fall.) on heifers varied significantly in relation to site topography and shelter. These crude site variables explained 65 98% of the variation in densities of horn flies and sheep head flies observed between pastures. Highest densities of Hydrotaea irritans were primarily associated with permanent, low-lying, fairly sheltered grassland sites, whereas the density was low in temporary, dry, wind-exposed pastures. A comparable relationship was found for Haematobia irritans. With Haematobosca stimulans (Mg.) and Morellia spp. no relation between grassland environment and fly density was detected. PMID- 8435483 TI - Changes in enzyme titres with age in four geographical strains of Aedes aegypti and their association with insecticide resistance. AB - The enzymes acetylcholinesterase, glutathione S-transferase (GST), glucose 6 phosphate dehydrogenase (G6PD), and general esterases were assayed in four strains of Aedes aegypti mosquitoes aged between 1 and 30 days. Microtitre plate methods were used to assay activity in the homogenates of individual mosquitoes. The levels of GST and G6PD declined with the age of the mosquitoes, while the activity for the other enzymes remained constant. Soluble protein content was also found to decline with mosquito age in all the strains. Insecticide bioassays showed that two strains (Trinidad and Virtudes) of Ae. aegypti were resistant to DDT, deltamethrin and malathion, whereas two other strains (Bangkok and Indian) were susceptible to all four classes of insecticides tested. Higher esterase activity levels in the resistant compared to the susceptible strains were assumed to be the cause of organophosphate resistance. The combination of DDT and deltamethrin resistance in two strains with normal GST and G6PD characteristics suggests that a kdr-type nerve insensitivity mechanism may be involved. PMID- 8435485 TI - Preliminary note on the distribution and ecology of Culicoides imicola in Portugal. AB - Data on Culicoides imicola were obtained during studies carried out during the recent outbreak of African horse sickness in Portugal. The previous most northerly published record of C. imicola in Portugal was 38 degrees 40'N (Pegoes). In the present work the geographical distribution of this species is extended to the parallel of 41 degrees 17'N. We have also confirmed the continuous presence of adult C. imicola in Southern Portugal (Alentejo and Algarve) throughout the year. In the laboratory we obtained this species from a sample of cattle faeces and from another of soil contaminated with animal excreta. In relation to host association 57.37% of C. imicola were trapped in the vicinity of pigsties. Finally, we collected 11,463 Culicoides of which 12.47% were C. imicola. PMID- 8435486 TI - The relative importance and distribution of Aedes polynesiensis and Ae. aegypti larval habitats in Samoa. AB - In preparation for a Filariasis Control programme in Samoa, during 1978 monthly larval surveys of the vector mosquito Aedes polynesiensis were carried out in four study villages in the main island of Upolu. A more extensive survey of larval habitat distribution was then made in twenty-two villages of Upolu and eighteen of Savai'i island, to determine the importance of habitat types according to their abundance, volume of water and whether their productivity was permanent or seasonal. Ae.aegypti larval densities and habitat distribution were also monitored and the occurrence of predatory Toxorhynchites amboinensis larvae in northern Upolu was recorded from forty-one collections. Aedes Breteau and container indices fluctuated with the pattern of rainfall in two coastal villages and an inland bush village, but not in a coconut plantation community. The five main Aedes larval habitat types encountered were: 200 litre water-storage drums, discarded tins and bottles, coconut shells, automobile tyres and treeholes. Aedes immatures occurred perennially in drums and tree holes, but breeding discontinued in tins, bottles and coconut shells during the driest month of July. For Ae. polynesiensis in Upolu the Breteau and container indices of 104.5 +/- SD 80.9 and 35.3 +/- 12.4 respectively were significantly higher than those in Savai'i: 33.1 +/- 25.0 and 24.3 +/- 20.0 respectively. Likewise for Ae.aegypti the Breteau and container indices of 50.8 +/- 32.5 and 23.9 +/- 15.6, respectively, were also significantly higher than those in Savai'i: 12.7 +/- 17.1 and 9.4 +/- 13.2 respectively. Habitat types greater or lesser importance were determined by plotting the percentage of each type of cotnainer utilized for Aedes breeding against the percentage of ech type amongst all larva-positive containers. Ae.polynesiensis preferred tree-holes but not water-storage drums. Ae.aegypti preferred drums and tyres; mixed populations of larvae of both species were commonest in these two types of habitat. Ae.polynesiensis occurred in every village. Ae.aegypti was encountered in all twenty-two villages surveyed in Upolu and nine of eighteen villages in Savai'i. Total larval surveys revealed that drums and tree-holes contained the highest numbers of Aedes larvae. The study provided criteria for planning a control programme. PMID- 8435487 TI - Allozyme analysis reveals six species within the Anopheles punctulatus complex of mosquitoes in Papua New Guinea. AB - Among samples collected from nineteen localities in Papua New Guinea, we have identified six species within the Anopheles punctulatus complex of mosquitoes, by means of cellulose acetate allozyme electrophoresis. An.punctulatus Donitz sensu stricto was collected from seven villages in the Madang area and from Buksak, Sausi Mission and an area 18 km SW of Tari; An.koliensis Owen from eight villages in the Madang area, from Popondetta and Brown River near Karema; and An.farauti No. 1 from ten coastal areas including Madang, Lorengau, Popondetta, Port Moresby, Rabaul and Wewak. Three newly recognized species, reported here for the first time, are designated as An.farauti No. 4 from Gonoa and Hudini, Madang area; An.farauti No. 5 from Ketarabo near Goroka; and An.farauti No. 6 from Hiwanda near Tari. Three other known members of the complex, An.clowi Rozeboom & Knight, An.farauti No. 2 (Bryan, 1973) and An.farauti No. 3 (Mahon & Meithke, 1982) were not detected in Papua New Guinea. Problems arising with morphological characters for the identification of species in this group are discussed. PMID- 8435488 TI - Electrophoretic keys to identify members of the Anopheles punctulatus complex of vector mosquitoes in Papua New Guinea. AB - Electrophoretic keys are given for the six species of the Anopheles punctulatus complex (Diptera: Culicidae) known from Papua New Guinea plus An.farauti No. 2 and No. 3 from Australia. The categories 'faster', 'standard' and 'slower' are used in keys to relate allozyme band migration following cellulose acetate electrophoresis to the standard pattern. Alternative keys are given depending on the availability of different species for use as standards. PMID- 8435489 TI - Blood-feeding of the gerbil flea Nosopsyllus laeviceps kuzenkovi (Yagubyants), vector of plague in Inner Mongolia, China. AB - The gerbil flea Nosopsyllus laeviceps (Wagner) (Siphonaptera: Ceratophyllidae) is an important Palaearctic vector of enzootic plague among sylvan and campestral rodents. Laboratory blood-feeding experiments with the subspecies N.l.kuzenkovi (Yagubyants) from Inner Mongolia, China, using three rodent species including the natural host Meriones unguiculatus (Milne-Edwards), demonstrated a positive relationship between per cent feeding and time allowed for feeding, particularly for female fleas. Also the bloodmeal size was proportional to sucking time and was significantly greater in females, which are larger, than in males. However, on all four strains of host tested, there was no significant correlation between the feeding success rate of the fleas and the amount of blood they imbibed. Fleas fed better on active compared to confined M.unguiculatus. These findings agree with studies of other flea species. PMID- 8435490 TI - Attracting adult New World screwworm, Cochliomyia hominivorax, to odour-baited targets in the field. AB - A field study in Libya investigated aspects of Cochliomyia hominivorax behaviour relevant to the operation of a target-based control system. Flies were readily caught by electrified targets, but only when baited with the attractant 'swormlure-4'. Target size (0.25-1 m2) did not affect catch, but black targets caught twice as many flies as red ones. Omitting the most volatile component of swormlure-4, dimethyl disulphide, significantly reduced catches of both sexes of C.hominivorax in wind-orientated traps, but only reduced the capture of females significantly on targets. A new polythene sachet dispenser for odours was tested; four to six such sachets filled with swormlure-4 less dimethyl disulphide gave an equivalent catch to one of the standard bottle plus wick dispensers using the same attractant, although they dispensed odour at about half the rate. From direct observations, fewer than 40% of flies contacted the target for more than 10 s on any one visit. From catches on an intermittently-active electrocuting grid, it was calculated that there is a c. 40% rate of multiple contacts of flies with the target. PMID- 8435491 TI - Fecundity of Anopheles tessellatus reduced by the ingestion of murine anti mosquito antibodies. AB - High titres of antibodies to antigens derived from head/thorax, midgut or abdomen of Anopheles tessellatus were produced in inbred mice. These antibodies, when ingested in a bloodmeal, reduced the fecundity of An. tessellatus by up to 29% in different experiments. It is postulated that antibodies directed against antigens shared between the head/thorax, abdomen and midgut tissues are involved in the reduction of fecundity. PMID- 8435492 TI - Susceptibility of the bedbug, Cimex lectularius, to selected insecticides and various treated surfaces. AB - Adult bedbugs, Cimex lectularius, were exposed for 24 h (25 degrees C) to filter paper treated with various dilutions of the technical grade of nine insecticides dissolved in acetone to determine the concentration-response relationships. The order of toxicity, from most to least based on the LC50's was: dichlorvos, pirimiphos methyl, lambda-cyhalothrin, bendiocarb, permethrin, malathion, carbaryl, tetrachlorvinphos, and fenvalerate. The residual toxicities of commercial formulations of six of the chemicals diluted with water and applied to wood, cardboard, cloth and galvanized metal, were determined by exposing adult bedbugs at 3, 7 and 12 weeks after treatment. The formulation of bendiocarb (FICAM 76% W) had little residual activity on all surfaces at 12 weeks after treatment. The formulation of carbaryl (SEVIN 21.5% L) was toxic to bedbugs on all surfaces at 12 weeks after treatment, but required high concentrations on wood, cardboard, and cloth. The formulation of pirimiphos methyl (ACTELLIC 57% EC) had no residual activity on any of the surfaces at 12 weeks after treatment. The formulation of tetrachlorovinphos (RABON 50% W) had residual activity for 12 weeks on all surfaces except metal. The formulation of permethrin (ATROBAN 11% EC) had residual activity on only metal and wood while the formulation of lambda cyhalothrin (KARATE 13.1% EC) had residual activity 12 weeks on all surfaces. PMID- 8435493 TI - Ecology of the biting midge Leptoconops albiventris in French Polynesia. I. Biting cycle and influence of climatic factors. AB - The diurnal biting cycle of Leptoconops albiventris de Meijere (Diptera: Ceratopogonidae) is described from beaches of Nuku-Hiva, French Polynesia. Biting activity increased during the morning, diminished during the afternoon and was sufficiently intense to constitute a nuisance throughout the whole day. Correspondence Analysis indicated that climatic factors influenced biting activity. Activity was initiated by and positively associated with sunshine, whereas high temperatures, increased wind speed and rainfall were factors limiting activity. Decreased density of females during the dry season and their low capacity for dispersal were considered potentially advantageous with respect to control. PMID- 8435494 TI - Ecology of the biting midge Leptoconops albiventris in French Polynesia. II. Location of breeding sites and larval microdistribution. AB - The habitat of the immature stages of Leptoconops albiventris de Meijere (Diptera: Ceratopogonidae) was found to be in beach sand located above the high tide level near creeping vegetation. The immatures were restricted to a narrow strip and most occurred in the upper 6 cm of sand. Within a given breeding site, larvae were aggregated in their distribution. Eggs were layed on the bare sand surface, from which the larvae apparently dispersed to the plant-covered sand and to deeper strata, before returning to the surface for pupation and emergence. The nature of these breeding sites suggests that it is possible to control L. albiventris populations. Recovery of immature stages from sand samples by a flotation method is described. PMID- 8435495 TI - Ecology of the biting midge Leptoconops albiventris in French Polynesia. III. Influence of abiotic factors on breeding sites. Towards ecological control? AB - Correspondance Analysis was used to determine the significant abiotic factors influencing the ecology of the immature stages of Leptoconops albiventris (Diptera: Ceratopogonidae). The breeding places required strict environmental conditions: fine and well-sorted sand, with low conductivity and humidity. However, the microdistribution of the immature stages within a breeding site does not depend on such factors. Modifying physical parameters in the larval breeding areas might be an important component in future ecological control programmes against L. albiventris populations. PMID- 8435496 TI - Reproductive success of cat fleas, Ctenocephalides felis, on calves as unusual hosts. AB - Cat fleas, Ctenocephalides felis, were released onto calves as unusual hosts, and sampled at intervals for histological examination. Egg output from fleas on age matched male and female calves was monitored. Using indicators of reproductive maturation and regression together with egg output data, the reproductive success and fertility of cat fleas on male and female calves were estimated. Comparisons were made with fleas taken from cats. The mean egg output of fleas on the bull calf was highly significantly different from that on the age-matched female calf: 28.14 +/- 2.96 (SE) eggs/h compared with 16.21 +/- 1.96 (SE) eggs/h. A higher proportion of sampled fleas (83.0%) was reproductively mature on the feline hosts compared with the calves (45.4-62.5%). Blue bodies resulting from oocyte resorption were present in the ovarioles of 10.4-19.0% of fleas sampled from the calves. No blue bodies were present in fleas removed from cats. Eggs laid by fleas on calves were viable and larvae were reared to adulthood. The mean percentage hatching success on the age-matched male and female calves was 46.7% and 51.7%. This represents a reduction in viability of 28-33% compared with eggs laid by fleas on cats. Factors which may account for reduced reproductive maturation of fleas on calves, including protein content of the host's blood, are discussed. PMID- 8435497 TI - Phlebotomine sandflies of Bangladesh: recent surveys. PMID- 8435498 TI - In situ conservation of diffusible elements in liver cells after cryofixation, cryosubstitution, and low temperature embedding at 193 K in HM23 lowicryl resin. PMID- 8435499 TI - Intracellular injection in fixed slices in combination with neuroanatomical tracing techniques and electron microscopy to determine multisynaptic pathways in the brain. AB - Intracellular Lucifer Yellow filling in fixed tissue has been recently introduced as a novel neuroanatomical approach to reveal the detailed morphology of individual neurons in isolated preparations of the central nervous system. Since dye injections are performed under visual control, the method is characterized by a high degree of inherent staining selectivity, thus circumventing the element of randomness often considered to be the crux of classical golgi-impregnation techniques. Moreover, the opportunity to optically monitor the injection procedure renders fixed slice preparations highly advantageous to be used in combination with retrograde fluorescent tracing. Subsequently, dye-filled neurons may be subjected to a simple photoconversion procedure leading to the intracellular formation of a stable polymer thus obtaining permanent specimens for light microscopy purposes. Due to the osmiophilic nature of the precipitate the photoconverted material is equally suitable for correlated electron microscopy, thus enabling the analysis of neuronal microcircuitry. At the ultrastructural level, sources of afferent input to identified projection neurons may be revealed by lesion-induced anterograde degeneration of synaptic terminals, therefore enabling the direct demonstration of multisynaptic links. Finally, morphologically identified neurons may be immunocytochemically characterized at the pre- and postembedding levels. It is therefore suggested that their methodological versatility and relative technical ease render intracellular fixed slice injections a promising complement to the catalogue of anatomical techniques. PMID- 8435500 TI - Ultrastructural and functional connectivity of intracellularly stained neurones in the vertebrate retina: correlative analyses. AB - A variety of intracellular recording and staining techniques has been used to establish structure-function and, in some cases, structure-function-neurochemical correlations in fish, turtle, and cat retinae. Cone photoreceptor-horizontal cell connectivity has been studied extensively in the cyprinid fish retina by intracellular staining with horseradish peroxidase (HRP) and subsequent electron microscopy. The available data suggest that horizontal cell dendrites around the ridge of the synaptic ribbon are postsynaptic, whilst finger-like extensions ("spinules") of lateral dendrites function as inhibitory feedback terminals. An interesting feature of this interaction is its plasticity: the feedback pathway is suppressed in the dark and becomes potentiated by light adaptation of the retina. Intracellular recordings and stainings of ganglion cells in both turtle and cat retinae have been possible. Prelabelling of ganglion cells by retrograde transport of rhodamine from the tectum allows ganglion cells to be stained under visual control, and their synaptic inputs determined by electron microscopy. Such studies have been extended to double labelling by using autoradiography or postembedding immunohistochemistry to identify the neurotransmitter content of the labelled cell and/or the neurotransmitter(s) converging upon it. It is envisaged that further applications of intracellular staining followed by double- or even triple-labelling will continue to enhance greatly our understanding of the functional architecture of the vertebrate retina. PMID- 8435501 TI - And the beat goes on. PMID- 8435502 TI - Medicine as ministry: reflections on a chaplaincy in India. PMID- 8435503 TI - Experiences at the interface between psychiatry and religion. PMID- 8435504 TI - Medicine and ethics at the crossroad: a Roman Catholic perspective. PMID- 8435506 TI - We are the elderly. PMID- 8435505 TI - My clergy, my doctor. PMID- 8435507 TI - The commonalities of religion and medicine. PMID- 8435508 TI - Was Lizzie Borden the victim of incest? PMID- 8435509 TI - Bicycle injuries in Rhode Island. PMID- 8435510 TI - A centenary 1893-1993. PMID- 8435511 TI - Cutaneous malignant melanomas with other coexisting neoplasms: a true association? AB - In the past, several authors described an association of cutaneous malignant melanoma (MM) with other neoplasms. As their results were not conclusive, we designed this study with the aim to determine whether the frequency and spectrum of coexisting neoplasms in patients with cutaneous MM are either a significant or a random event. Therefore, the histories of 623 patients with primary MM from our clinic have been evaluated by a direct questionnaire. Diagnosis of MM has been established by histologic examination after excisional biopsy. The male/female (M/F) ratio was 240/383, the mean age 52.5 years (range 14-93). The distribution of risk groups yielded 277 patients (M/F = 90/187) for low risk (Breslow < 0.75 mm trunk, < 1.50 mm extremities), 245 patients (M/F = 105/140) for intermediate risk (Breslow 0.76-3.00 and 1.51-5.00 mm, respectively). 101 patients (M/F = 45/56) for high risk (Breslow > 3.00 and > 5.00 mm, respectively). 64 patients (10.3%) had associated primary carcinomas including 7 patients with 2 primary carcinomas compared to a control group (n = 313) with 12 carcinomas (3.8%). 50% of the carcinomas were diagnosed before the diagnosis of melanoma. The M/F ratio of this group was 25/39, the mean age at diagnosis of MM 62.7 years (range 28 91), the mean age at diagnosis of carcinoma 55.6 years (range 29-90). In the female group, breast cancer predominated (18/39), followed by uterus (7/39) and basal cell carcinoma (7/39); in the male group, basal cell carcinoma (10/25) was followed by prostate cancer (6/25).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8435512 TI - Comparison of the pathology of fascia in eosinophilic myalgia syndrome patients and idiopathic eosinophilic fasciitis. AB - The L-tryptophan eosinophilic myalgia syndrome (EMS) clinically has some similarities with idiopathic eosinophilic fasciitis (EF). In order to study the pathology of both syndromes, we analyzed 21 biopsies of patients with EMS and 8 with idiopathic EF. In both diseases there is dermal and fascial mucin and dermal edema, but this was more common in EMS. EMS is also characterized by dilated lymphatics, dermal and septal sclerosis and macrophage-rich inflammation. Neural inflammation was seen in 4 of the cases with EMS and in none with idiopathic EF. In both syndromes, there are many histopathological similarities. The differences may be due to sampling and to sample size. The nerve lesions of EMS may result from the nature of lymphocyte-macrophage inflammation, or the effect of the eosinophil neurotoxin and may not be a primary event. PMID- 8435513 TI - Severity scoring of atopic dermatitis: the SCORAD index. Consensus Report of the European Task Force on Atopic Dermatitis. AB - BACKGROUND: Assessment methods for atopic dermatitis (AD) are not standardized, and therapeutic studies are difficult to interpret. AIMS: To obtain a consensus on assessment methods in AD and to use a statistical method to develop a composite severity index. METHODS: Consensus definitions were given for items used in the scoring system (extent, intensity, subjective) and illustrated for intensity items. Slides were reviewed to address within- and between-observer variability by a group of 10 trained clinicians, and data were statistically evaluated with a two-way analysis of variance. Two variants of an assessment system were compared in 88 patients at 5 different institutions. Data were analyzed using principal-component analysis. RESULTS: For 5 intensity items studied (erythema, edema/papulation, oozing/crusts, excoriations, lichenification), within- and between-observer variability was good overall, except for edema/papulation which was difficult to assess with slides. In the series of 88 patients, principal-component analysis allowed to extract two unrelated components: the first one accounting for 33% of total variance was interpreted as a 'severity' component; the second one, accounting for 18% of variance, was interpreted as a 'profile' component distinguishing patients with mostly erythema and subjective symptoms and those with mostly lichenification and dryness and lower subjective symptoms. Of the two evaluation systems used, the one using the rule of nine to assess extent was found more workable than the one using a distribution x intensity product. A scoring index (SCORAD) combining extent, severity and subjective symptoms was mathematically derived from the first system and showed a normal distribution of the population studied. CONCLUSION: The final choice for the evaluation system was mostly made based on simplicity and easy routine use in outpatient clinics. Based on mathematical appreciation of weights of the items used in the assessment of AD, extent and subjective symptoms account for around 20% each of the total score, intensity items representing 60%. The so-designed composite index SCORAD needs to be further tested in clinical trials. PMID- 8435514 TI - Evolving pattern of drug-induced toxic epidermal necrolysis. AB - A series of 90 consecutive cases of toxic epidermal necrolysis (TEN) observed in a single center between 1985 and March 1991 was compared to a previous series from the same institution in order to look for changes in the characteristics of the patients and in the drug etiology. The most salient change was the high prevalence of human immunodeficiency virus (HIV) infection among patients with TEN (20/90). This high rate of HIV infection was linked to two other changes: higher number of male patients leading to an equilibrated sex ratio and an increased role of sulfonamides-mainly sulfadiazine-as etiologic agents. PMID- 8435515 TI - Effects of all-trans-retinoic acid on melanocyte adhesion and motility. AB - Human epidermal melanocytes were treated with all-trans-retinoic acid (RA) and examined for adhesion to bovine serum albumin-, fibronectin- and laminin-coated culture dishes. Control and treated cells were also examined for motility into micropore filters coated with the same proteins. Treatment of the cells with 3 x 10(-6) M RA for 3-4 days resulted in inhibition of attachment to all three substrates. Decreased attachment was observed within 1.5 h. Inhibition of attachment was not due to toxicity because differences between control and treated cells disappeared by 18 h, when most of the cells (approximately 75%) were attached and spread on all three substrates. The same treatment that inhibited adhesion also reduced migration into the interstices of micropore filters coated with the same three proteins. In additional experiments, human and mouse melanoma cell lines were examined in place of normal melanocytes. RA treatment also blocked adhesion and motility of these cells. The malignant melanoma cells were less sensitive to RA than normal melanocytes in the adhesion assay but were equally sensitive in the motility assay. The ability of RA to inhibit melanocyte adhesion and motility as well as melanocyte growth could explain, in part, the capacity of retinoids to modulate melanocyte function in hyperpigmented skin lesions. PMID- 8435516 TI - In vivo confocal microscopy: a new paradigm in dermatology. PMID- 8435517 TI - In vivo vision of the human skin with the tandem scanning microscope. AB - The tandem scanning reflected light microscope invented by Petran and Hadravsky provides real-time vision in the confocal mode. It performs nondestructive optical sectioning of biological material to a depth that depends on the transparency of the tissue. This real-time facility adds a fourth dimension (time) to the study of living specimens. In the present work, human skin was explored in vivo, at the cellular level to a depth of 150 microns. Two different anatomical sites were investigated: the back of the hand and the volar aspect of the forearm. The stratification of the horny layers, the nuclei of the living keratinocytes through the whole epidermis and the capillary loops within the superficial dermis constituted clear reference points. These permitted thickness measurements of the stratum corneum and epidermis to an accuracy of 1 microns. This method of exploration provides a new challenge for dermatologists and cosmetologists. PMID- 8435518 TI - Azelaic acid has antimycotic properties in vitro. AB - Azelaic acid is a therapeutic agent with well-known antibacterial properties, but its antimycotic effect has not yet been investigated systematically. In this study we have used an agar dilution technique to test the inhibitory effect of azelaic acid upon common dermatophytes, Scopulariopsis brevicaulis, Candida albicans, Candida glabrata and Pityrosporum ovale. As a result, the growth of dermatophytes and S. brevicaulis was suppressed by 0.56% azelaic acid and that of P. ovale by 1%. By 4% azelaic acid C. glabrata was inhibited completely, but C. albicans still maintained some growth. The antimycotic effect of azelaic acid occurred at pH values between 4.8 and 5.5, whereas its disodium salt had no such effect at pH 6.1. Considering the favorable pharmacological data of azelaic acid, our results give reason to investigate the antimycotic effect of this agent in vivo. PMID- 8435519 TI - Onychomycosis: successful treatment with once-weekly fluconazole. AB - We report a case of fingernail onychomycosis in an immunosuppressed renal transplant patient who was successfully treated with once-weekly fluconazole therapy. Relapse did not develop over the 2-month follow-up period. There were no adverse effects from therapy and the cyclosporin dose did not require adjustment. This case suggests that fluconazole may play a role in the treatment of onychomycosis with once-weekly dosing schedules. Future large-scale clinical trials are indicated to fully evaluate its safety and efficacy in onychomycosis. PMID- 8435520 TI - Clinical investigation of skin microcirculation. AB - Skin microcirculation is rather complex. The skin viability depends upon the nutritional circulation, which cannot be assessed by conventional macrocirculatory methods that evaluate total blood supply. The indisputable advantage of the microcirculatory methods is to provide information directly in diseased skin areas and assess the effectiveness of vasoactive drugs where they are supposed to act. Several techniques are available today to evaluate the skin microcirculation. Among them, capillaroscopy and transcutaneous measurement of the partial oxygen pressure are of special interest because they provide information which is directly useful in clinical practice. Other techniques remain experimental. In this paper, the main microcirculatory techniques are reviewed and their clinical implications discussed. PMID- 8435521 TI - Therapeutic efficacy of oral low-dose cyclosporin A in severe psoriatic arthritis. AB - Six male patients with severe psoriatic arthritis (PA) unresponsive to various topical and systemic therapies have been treated with oral cyclosporin A (CyA; Sandimmun) solution at daily doses ranging usually from 1.5 to 5.0 mg/kg. In 1 case the dose had to be increased to 7 mg/kg/day. At initiation of CyA therapy skin involvement was between 40 and 90% of total body surface. Initiation of CyA therapy resulted in marked improvement of skin lesions within 2-7 weeks accompanied by impressive relief from arthralgias and improvement of joint function. The requirement for nonsteroidal anti-inflammatory drugs was markedly reduced in all cases. All patients in whom CyA therapy was continued remained clinically stable for several months (follow-up period 2-7 months). Although mild to moderate relapses occurred, rebound phenomena were not observed after discontinuation of treatment. Side effects which comprised serum creatinine increases in 3 out of 6 cases were reversed by adjustment of CyA dosage. PMID- 8435522 TI - Epidermolysis bullosa simplex Dowling-Meara: troublesome blistering and pruritus in an adult patient. AB - A 46-year-old woman with the Dowling-Meara variant of epidermolysis bullosa simplex (DM-EBS) presented with worsening recurrent, pruritic, circinate crops of clear and haemorrhagic herpetiform blisters affecting her trunk and limbs. Electron microscopy showed tonofilament aggregation and an intra-epidermal level of blister formation confirming a diagnosis of DM-EBS rather than an acquired immunobullous disorder. Antihistamines failed to control the intense pruritus, but dapsone (up to 150 mg daily) was beneficial. Mutations of basal cell keratin genes (K14 and K5) are thought to be of aetiopathological significance in this form of epidermolysis bullosa, but the underlying cellular mechanisms responsible for the clinical deterioration and severe itching in this adult patient are not yet clear. PMID- 8435523 TI - Primary infection by human parvovirus B19. AB - We describe a case of primary infection by human parvovirus B19 in a 20-year-old woman; it manifested as erythemato-maculo-papular lesions, pharyngotonsillitis, lymphadenopathy, fever, arthralgia and myalgia, asthenia and anorexia. Laboratory tests revealed anaemia, leucopenia, thrombocytopaenia and a rise in some inflammatory indices. Elisa test was positive for anti-human parvovirus B19 IgM. Clinical symptoms spontaneously regressed in 2 weeks. Thirty days after hospital admission all the laboratory tests returned to normal values; furthermore, specific IgM and IgG were detectable. PMID- 8435524 TI - Acute generalized exanthematous pustulosis due to doxycycline. AB - Sterile epidermal neutrophilic pustulation can be observed in a variety of diseases. Though drug hypersensitivity is an uncommon cause, it is yet a known entity to be considered in the differential diagnosis of generalized pustulosis. In a 40-year-old woman, who developed a generalized pustular eruption after starting on doxycycline therapy of bronchitis, the rash was concluded to be drug induced after exclusion of other pustular dermatoses. Sensitization to doxycycline was demonstrated by in vitro lymphocyte testing and correlated with clinical drug hypersensitivity after recurrence of the pustular eruption on nonintentional rechallenge with doxycycline. PMID- 8435525 TI - Topical podophyllotoxin in psoriasis vulgaris. PMID- 8435526 TI - Positive response to 5HT-2 antagonists in a family affected by epidermolysis bullosa Dowling-Meara type. PMID- 8435527 TI - Ethical dilemmas in qualitative research: how do we respect autonomy? AB - This essay brings the concept of nursing research into light and in particular examines the principle of 'respect for autonomy', its relationship and limitations in the field of research on human subjects during qualitative research. This essay will also identify how ethical dilemmas, involving respect for autonomy, can develop during research and a systematical method of critical ethical analysis will be presented to demonstrate how nurse researchers can resolve such issues, if and when they arise. It is necessary to focus on one facet of the research process to illustrate the 'depth' of consideration required to ensure that such research is of the highest quality. PMID- 8435528 TI - Nasal catheters for oxygen administration. An audit of safety and patient comfort. AB - This audit was designed to assess the feasibility of using nasal catheters in the recovery room as a method of oxygen delivery. The two main tenets of feasibility were patient safety, as reflected by oximetry, and patient comfort. PMID- 8435529 TI - Dusting powder in surgeon's gloves. A historial review. AB - The use of surgical gloves for any surgical procedure, or any event which may involve the spillage of body fluids, is now well known and even expected. In these days of HIV and other infectious diseases, protection for the patient is as important as protection for the carer and it is therefore vital that the gloves/protection will not impart any harm either to the person wearing them or to the person who is being touched. PMID- 8435530 TI - A cause for concern. PMID- 8435531 TI - Counselling and the nurse. AB - The brief which I was given for the writing of this short piece was to write about counselling, slanting it towards the needs of nurses. On the face of it, this seems to be an entirely reasonable request. After all, my business is counselling and this journal will chiefly be read by nurses. Yet, for some reason which I could not at the time analyse, I felt a vague sense of unease at the task as it had been defined. Giving it some thought, I came to the conclusion that this unease was to do with the notion that such a brief might imply that nurses were somehow different to the rest of human kind. They are not, of course. However, I sometimes think that they believe themselves to be different and this is an idea to which I will return later. First, however, I wish to write about what I think counselling is and, by implication, what I think it is not and how personal circumstances may impinge on a working situation. PMID- 8435532 TI - Theatres--the power and the gory? AB - It is over ten years since the Centres for Disease Control (CDC) in Atlanta Georgia became aware of the first cases of what has now been recognised as the global pandemic of AIDS. There have now been reports from over 170 countries and the World Health Organisation estimates that 13 million people have been infected by the virus. This new threat has created enormous challenges for all health care workers; in addition to being a newly recognised disease the issues raised by HIV and AIDS touch upon every taboo in our society. Traditionally these are issues which have been badly handled by many healthcare workers. Of these the most obvious is death and dying of young people (25% of people with HIV are under 24 years old), but they also include drug use and the old chestnuts of sex and sexuality. The disease has tested the strengths of both individuals and organisations. All too often the cracks have shown. PMID- 8435533 TI - What's in a word? PMID- 8435534 TI - Provision of a designated list for HIV services. PMID- 8435535 TI - Developing a professional profile. PMID- 8435536 TI - The introduction of universal precautions against infection and the use of activated glutaraldehyde. PMID- 8435537 TI - Universal precautions in the operating department. AB - Those operating theatre personnel who aim to keep up to date by reading the professional journals may well be confused and feel uninformed about the concept of universal precautions. While some authors focus on universal precautions, they do not mention operating theatres. Others continue to discuss the Human Immunodeficiency Virus (HIV), the Hepatitis B Virus (HBV) and high risk patient's. Furthermore the practical aspects of the implementation of universal precautions have not, to date, been thoroughly documented, other than the vague advice of 'treat every patient the same'. This article aims to clarify the concept of universal precautions, consider why they are needed, and suggest a possible pathway for their implementation. The three main changes in practice will also be discussed. PMID- 8435538 TI - [Methodology in psychiatric epidemiologic research]. AB - Crucial epidemiological variables are described: incidence, prevalence, and relative risk. Of primary importance to comparison of rates of illness and testing hypotheses as to its causes and course are the exact identification and definition of mental disorders. In recent years a variety of screening instruments for assessing both general mental impairment and specific mental disorders have been developed. The methodological standards demanded of a good screening instrument are discussed, namely, the identification of all actual cases of illness (as far as possible) without too many false positive findings among the healthy persons examined. PMID- 8435539 TI - [Incidence of psychiatric diseases in the patient sample of a general practitioner--a case study of ambulatory management of psychiatric patients]. AB - A prevalence study carried out in Berlin aimed at determining the incidence and distribution of psychiatric diseases among the patients treated by a general practitioner. A questionnaire had to be completed by the patient and by the physician at every consultation. This form comprised not only questions regarding the patient's main concern and self-assessment in respect of physical and mental complaints, but also a list of actual signs and symptoms of physical and mental disorders as well as questions on demographic and social variables. The physician was asked to state details on findings, principal and secondary diagnoses, kinds of therapy and also the time the consultation lasted. The results show clearly that psychiatric diseases occur in the general practitioner's consultation-room and in his practice in a proportion that is large indeed; and that the patients' self-assessment regarding the predominantly" or exclusively" mentally conditioned nature of their complaints and the formulation of their main mental concern of frequent affirmative answers in the list of mental complaints largely correlated with the statements regarding mental or psychiatric findings or principal diagnosis made by the physician. There were also clear interrelations with demographic and social variables, particularly in connection with the kinds of therapy that had been selected. On the whole, this study showed once again clearly that mentally diseased patients do not receive all the satisfactory and appropriate treatment of which they stand in need. PMID- 8435540 TI - [Epidemiologic public health conclusions from observations of illnesses caused by Salmonella enteritidis]. AB - 11 Persons fell ill after having eaten a cream cake, prepared from two hen's eggs just after buying. One of the eggs must have contained about a thousand million of S. enteritidis, according to the concentration of bacteria found in the frozen cream. A 41-year old cook without any predisposition got septicemia by S. enteritidis after tasting a mixture of refrigerator-cooled eggs and minced meat, bought one day previously. 9 of 57 diseased inmates of an old-age home died from S. enteritidis infections after eating a strawberry cream with whipped whites of eggs. The following requirements are mandatory, as concluded from observations made during these incidents: Hen's eggs should be stored in a refrigerator already before they are sold, and the time of storage should be limited to two weeks. Pasteurized egg products should be offered also in the retail trade. To improve detection of sources of infection it would be necessary to store a sample of each lot of feed in farms with layer flocks or with other big livestock and in the feed mills. The most important measure would be the prescription of a general decontamination of the mixed feed just before supplying it to the farmer. PMID- 8435541 TI - [Epidemiologic and clinical aspects of HIV infection in homosexual patients and intravenous drug addicts in a comparative study]. AB - The clinical course of HIV-infection was analysed in a group of homosexual patients (n = 76, 72%) compared to intravenous drug abusers (IVDA, n = 30, 28%) in a retrospective cross-sectional study. The mean age of homosexual patients was 37.5 years compared to 28 years for IVDA. The following diseases are found significantly more frequently in homosexual patients compared to IVDA: Pneumocystis-carinii pneumonia (PCP) 17.1% vs. 0% (p < 0.05); Kaposi' sarcoma 16% vs. 0% (p < 0.05); diarrhoea 47.4% vs. 23.3% (p < 0.05); oral candidiasis 51.3% vs. 23.3% (p < 0.01); non-specific pneumonia of bacterial aetiology or due to unknown organisms 30% vs. 0% (p < 0.001) und seborrhoeic dermatitis 13.2% vs. 0% (p < 0.05). In contrast, viral hepatitis, non-specific abscesses and gonorrhoea were seen significantly more often in IVDA. The data show clearly that the spectra of HIV-associated diseases and HIV-unconnected diseases are significantly different in the two main groups. A risk-oriented preventive prophylaxis of HIV related diseases and other infections is therefore required for each of these groups. PMID- 8435542 TI - [Utilization of anonymous HIV testing by the federal health office--developments and motives]. AB - In the state-run health office in Ulm a survey of the frequency of anonymous HIV antibody tests was taken between 1985 to 1991, of the age and gender representation from 1988 to 1991, of the test motives from 1.1.1990 to 1.3.1991. The result was a regressive trend following the test boom of 1987 and 1988, which is becoming more and more stable. The relation of men and women has been amounting to 6:4 in the last four years; the proportion of women receding slightly but constantly. The main motive of being tested was finding out about a high-risk or potentially high-risk sexual contact, mostly at the beginning of a new partnership. The motive ranking second in frequency was the investigation of the consequences of blood exposure, mostly relating to medical work. The third place was taken by irrational anxieties as a test motive. The article discusses the fact that test at the beginning of a new partnership frequently have the meaning of a sacrifice and a symbol of bondage in combination with a vow to be faithful. In case of irrational anxieties about AIDS the test-counsellor gets a chance to diagnose a possibly neurotic development at a very early stage, so that painful and expensive chronification and generalisation could be stopped or eased. PMID- 8435543 TI - [Experience with preventive measles, mumps and rubella vaccination in unified Germany]. AB - Considerable immunity gaps in respect of mumps and rubella (German measles) of up to 30% among pupils of the prepuberty age are the requisite arguments in favour of the need for vaccination measures. Combined protective vaccination with live attenuated measles-mumps-rubella vaccine without preceding laboratory tests is recommended for practical reasons and economy. No side effects have been seen on renewed protective vaccination with live attenuated measles vaccine in case of already existent natural immunity. A booster effect can be demonstrated in vaccinated persons with low or borderline antibody levels. Revaccination from the 6th year of life onwards is recommended and advocated to close existing vaccination and immunity gaps. PMID- 8435544 TI - [The concept of environmental pollution for emission control in regulating carcinogenic air pollutants in outdoor air]. AB - The Conference of Ministers for the Environment commissioned a working group of the Lander Committee for Immission Protection to develop a concept of guidelines for the concentration of carcinogenic pollutants in the atmospheric aerosol. Of the large number of substances which have been identified as carcinogenic, seven were selected (arsenic, asbestos, benzene, cadmium, diesel exhaust, polynuclear aromatic hydrocarbons and 2,3,7,8-tetrachlorodibenzo-(p)-dioxin). These substances are emitted into the environment by amounts that are quantitatively of special importance for immission control. There are standardised measuring procedures for controlling them and their toxicological data base permits a quantitative assessment of cancer risk. The quantitative risk assessment by the working group was based on the WHO's "unit risk" model. It was decided that for evolving the guidelines the total cancer risk for all carcinogenic air pollutants be limited while at the same time the possible risk attributed to each individual substance should be reduced according to its contribution to the actual total cancer risk. The synthetic model developed by the working group is explained in detail and the resulting guidelines for an acceptable total cancer risk of 1:1000, 1:2500 und 1:5000 are stated. PMID- 8435545 TI - [Data protection and data access (II): Physician's responsibility for confidentiality, federal statistics law and data collection by authorization with reference to implementing occupational medicine epidemiologic studies in Germany]. AB - The additional legal rulings governing access to personal data for epidemiological research are the medical professional secrecy regulators and the federal statistics law. These permit access to personal data only if the individual has given his or her informed constant. Beyond this, both laws contain clauses governing the transfer of anonymous data for research and science. Thus anonymized data may be transferred on request to authorized persons or institutions, such as a physician or the regional statistics office. Finally, a custodian model is presented which provides further possibilities for research in occupational medicine and epidemiology within this very restrictive legal framework. PMID- 8435546 TI - Organisation of perinatal/neonatal care. AB - There is no single system, whether state run, private or mixed, that consistently produces superior perinatal results (131), although these usually emanate from jurisdictions with regionalised or centralised comprehensive antenatal and natal care, as opposed to haphazard systems of care. Again the literature is "more description than evaluation, possibly because the latter requires comparative studies or audits which have not caught up with the new technology" (132). Changes in the organisation and delivery of reproductive health care since 1960, combined with advances in treatment, have apparently had an impact on the outcome of pregnancy and newborn care, resulting in reductions in perinatal mortality, mainly through their influence on birthweight-specific mortality. The latter is a major marker of the quality of hospital reproductive health care. Changes in the distribution of weights at birth have been relatively small; consequently the proportional numbers of infants born weighing less than 1500 g, who contribute most to morbidity and mortality, has roughly tracked the birth rate and has changed little. The proportion of babies born of low weight due to prematurity and/or intrauterine growth restriction, which are mainly influenced by socioeconomic and environmental factors, has seen only a marginal reduction in most developed countries and cannot explain the fall in mortality. Many reviews (e.g. 31, 36-38, 40, 41, 43-45, 47-52, 54, 55, 66, 67, 90, 93-95) of perinatal care now accept the cause and effect relationship between enhanced perinatal care and decline in perinatal mortality. Reduction in the incidence of low birthweight between 1500 and 2500 g is attributed more to the influence of environmental and lifestyle factors, including the standard of living, housing and nutrition, the level of education and the prevalence of infections in the population. On the other hand, the incidence of infants born weighing less than 1500 g, the major contributors to perinatal morbidity and mortality in developed societies, is relatively stable across time and across different jurisdictions. It forms about 1% of all births, but is responsible for 60-75% of morbidity and mortality. It appears relatively insusceptible to improvements in standards of living and other environmental factors. It may be more dependent on biological factors controlling the onset of premature labour, the incidence of genetic or chromosomally determined disease and the prevalence of teratogens. The only way to influence these factors is through a better understanding of the mechanisms by which they operate, which should lead to the appropriate strategy for their elimination.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8435547 TI - Index Medicus and Canadian Family Physician. PMID- 8435548 TI - Colorectal cancer. Can we lower the death rate in the 1990s? AB - Colorectal cancer is second only to lung cancer in the number of lives it claims annually, yet it is a curable cancer. Early detection is possible in high-risk individuals. The risk for colorectal cancer almost doubles every 7 years in patients older than 50. The authors review the epidemiology and site distribution of colorectal cancer, compare available diagnostic techniques, and consider the cost effectiveness of screening. Barium enema and endoscopy are recommended diagnostic tests, but expensive colonoscopy does not appear to be justified for screening. PMID- 8435549 TI - Treating non-insulin-dependent diabetes. Oral agents or insulin? AB - This article describes suggested treatment regimens for non-insulin-dependent diabetes mellitus. Diet is usually the first-line therapy. If this fails, most patients should be given a trial of oral agents, usually sulfonylurea first. Sulfonylurea and metformin can be combined if necessary. If oral agents fail, insulin is indicated. Insulin and an oral agent sometimes are used together. PMID- 8435550 TI - [Urticaria and antihistamines]. AB - Urticaria is often incapacitating, yet it is not always easy to know whether a patient should undergo testing and what treatment should be prescribed. This article provides a systematic approach to urticaria and its treatment. PMID- 8435552 TI - Achieving healthy weights. AB - Only 5% of patients dieting to achieve permanent weight loss will be successful and reap the associated health benefits. Ninety-five percent will be unsuccessful. The health implications of failed dieting attempts are numerous and include negative effects on both physical and psychological well-being. Better alternatives to dieting help patients take small, positive, enjoyable steps toward healthy eating, active living, and a positive self-image. PMID- 8435551 TI - Women and obesity. Learning to live with it. AB - Chronic dieting is not free of risks. Relevant literature is assessed to aid in making the decision about whether an obese woman should attempt weight loss repeatedly. Alternative strategies to weight loss are offered that shift the focus from weight loss to stabilization and from dieting to normalizing eating patterns and intake. PMID- 8435553 TI - Health hazards in medical institutions. Family physicians' role in hospital occupational health. PMID- 8435554 TI - Leading the community. Newfoundland's HIV scenario. PMID- 8435555 TI - We've come a long way. PMID- 8435556 TI - Appropriate use of hypodermoclysis. PMID- 8435557 TI - Elderly patients and benzodiazepines. PMID- 8435558 TI - Practice guidelines: are they necessary? PMID- 8435559 TI - Advanced but expensive technology. Balancing affordability with access in rural areas. PMID- 8435560 TI - Radiology rounds. Fibrous dysplasia. PMID- 8435561 TI - Dermacase. Chronic radiation dermatitis. PMID- 8435562 TI - Community site development for family medicine residency programs. PMID- 8435563 TI - Prenatal screening for hepatitis B surface antigen. Is universal screening necessary? AB - Prenatal screening for hepatitis B is now recommended as a universal practice in Canada. This study questions whether that policy should apply outside large urban centres. We studied women delivering babies at the Royal Victoria Hospital in Barrie, Ont. Of 1216 women, results of HBsAg screening were available for 716; only two women, both from a high-risk group, were HBsAg positive. If selective screening is used, physicians must question patients carefully to ensure that women at risk are identified and tested. PMID- 8435565 TI - Mammography: reviewing the evidence. Epidemiology aspect. AB - The role of mammography as a screening test for breast cancer is still being evaluated. Screening does not seem to reduce breast cancer mortality in women age 40 to 49. However, for women age 50 to 69, a 40% reduction in breast cancer mortality can be anticipated after 5 years, providing high compliance to screening is obtained. PMID- 8435564 TI - Breast cancer screening for women younger than 40. AB - The charts of 661 women aged 15 to 39 revealed that almost 50% of teenage patients had had breast screening examinations. Most of the physicians and residents involved began performing and teaching breast examination to patients in their teens. Concerned that it might do more harm than good, the Canadian guidelines do not advocate early screening. PMID- 8435566 TI - Chlamydia trachomatis during pregnancy. To screen or not to screen? AB - A critical review of the literature on screening for and treating Chlamydia trachomatis during pregnancy suggests that all pregnant women at high risk of chlamydial infection, or from a population where infection is prevalent, should be screened and treated. This will help reduce chlamydial infections in infants and may decrease adverse outcomes of pregnancy. PMID- 8435567 TI - Save the normal foreskin. PMID- 8435568 TI - Ethnic differences in mortality from sudden infant death syndrome in New Zealand. AB - OBJECTIVES: To examine the factors which might explain the higher mortality from sudden infant death syndrome in Maori infants (7.4/1000 live births in 1986 compared with 3.6 in non-Maori children). DESIGN: A large nationwide case control study. SETTING: New Zealand. 485 infants who died of sudden infant death syndrome were compared with 1800 control infants. There were 229 Maori and 240 non-Maori cases of sudden infant death syndrome (16 cases unassigned) and 353 Maori and 1410 non-Maori controls (37 unassigned). RESULTS: Maori infants had 3.81 times the risk (95% confidence interval 3.06 to 4.76) of sudden infant death syndrome compared with non-Maori infants. The risk factors for sudden infant death syndrome within groups were remarkably similar. When Maori and non-Maori controls were compared the prevalence of many of the known risk factors was higher in Maori infants. In particular, mothers were socioeconomically disadvantaged, younger, and more likely to smoke and their infants were of lower birth weight and more likely to share a bed with another person. Multivariate analysis controlling for potential confounders found that simply being Maori increased the risk of sudden infant death syndrome by only 1.37 (95% CI = 0.95 to 2.01), not statistically significantly different from 1. Population attributable risk was calculated for prone sleeping position, maternal smoking, not breast feeding, and infants sharing a bed with another person. In total these four risk factors accounted for 89% of deaths from sudden infant death syndrome in Maori infants and 79% in non-Maori infants. CONCLUSION: The high rate of sudden infant death syndrome among Maori infants is based largely on the high prevalence in the Maori population of the major risk factors. Other risk factors, not related to ethnicity, probably explain remaining differences between Maori and non-Maori children. PMID- 8435569 TI - Sudden infant death syndrome: links with infant care practices. AB - OBJECTIVES: To investigate infant care practices in a small ethnic minority population within Britain that might suggest possible factors contributing to the low incidence of the sudden infant death syndrome in Asian populations. DESIGN: Ethnographic interviewing, a qualitative comparative method drawn from social anthropology. SETTING: Central Cardiff. SUBJECTS: Non-random sample of 60 mothers of Bangladeshi or Welsh ethnic origin and working or middle class occupational status, who had infants under one year old. None of the families interviewed had experienced a sudden infant death. RESULTS: Broad cultural contrasts emerged as a series of themes from the interview data: living patterns, family networks, sleeping patterns, and concepts of time and dependence. CONCLUSION: Bangladeshi infants were cared for in a consistently rich sensory environment; Welsh infants, in contrast, were more likely to experience alternating periods of high and low sensory input. Long periods of lone quiet sleep may be one factor that contributes to a higher rate of sudden deaths in white than in Asian infants. PMID- 8435570 TI - A counsellor in every practice? PMID- 8435571 TI - Investigation of inheritance of chronic inflammatory bowel diseases by complex segregation analysis. AB - OBJECTIVE: To investigate the mode of inheritance of ulcerative colitis and Crohn's disease by complex segregation analysis. DESIGN: Cross sectional population based survey of familial occurrence of chronic inflammatory bowel disease. SETTING: Population of the Copenhagen county in 1987. SUBJECTS: 662 patients in whom inflammatory bowel disease had been diagnosed before 1979, of whom 637 (96%) provided adequate information. Of 504 patients with ulcerative colitis, 54 had 77 relatives with ulcerative colitis and of 133 patients with Crohn's disease, five had seven relatives with Crohn's disease. MAIN OUTCOME MEASURES: Patterns of segregation of either disease as assessed by complex segregation analysis performed with the computer program POINTER. RESULTS: The analysis suggested that a major dominant gene with a penetrance of 0.20-0.26 is present in 9-13% of adult patients with ulcerative colitis. The analysis did not allow for other components in the familial aggregation. For Crohn's disease the best fitting model included a major recessive gene with complete penetrance, for which 7% of the patients are homozygous. However, this model was not significantly different from a multifactorial model. CONCLUSIONS: The segregation pattern indicates that a major dominant gene has a role in ulcerative colitis, and suggests that a major recessive gene has a role in Crohn's disease. PMID- 8435572 TI - Initiation of hypertension in utero and its amplification throughout life. AB - OBJECTIVE: To determine whether the relation between high blood pressure and low birth weight is initiated in utero or during infancy, and whether it changes with age. DESIGN: A longitudinal study of children and three follow up studies of adults. SETTING: Farnborough, Preston, and Hertfordshire, England, and a national sample in Britain. SUBJECTS: 1895 children aged 0-10 years, 3240 men and women aged 36 years, 459 men and women aged 46-54 years, and 1231 men and women aged 59 71 years. The birth weight of all subjects had been recorded. MAIN OUTCOME MEASURE: Systolic blood pressure. RESULTS: At all ages beyond infancy people who had lower birth weight had higher systolic blood pressure. Systolic blood pressure was not related to growth during infancy independently of birth weight. The relation between systolic pressure and birth weight became larger with increasing age so that, after current body mass was allowed for, systolic pressure at ages 64-71 years decreased by 5.2 mm Hg (95% confidence interval 1.8 to 8.6) for every kg increase in birth weight. CONCLUSIONS: Essential hypertension is initiated in fetal life. A raised blood pressure is then amplified from infancy to old age, perhaps by a positive feedback mechanism. PMID- 8435573 TI - Why are children referred for circumcision? PMID- 8435574 TI - Counsellors in English and Welsh general practices: their nature and distribution. AB - OBJECTIVE: To establish the prevalence of counselling services in English and Welsh general practices and factors associated with their distribution; to describe qualifications, working arrangements, and case mix of "counsellors." DESIGN: Postal questionnaire and telephone interview survey of a sample of about one in 20 general practitioners in England and Wales. SETTING: English and Welsh general practices. SUBJECTS: 1880 general practitioners of whom 1542 (82%) completed questionnaires. MAIN OUTCOME MEASURES: Prevalence and distribution of practice counselling services; counsellors' qualifications and funding; types of patients referred. RESULTS: 586 counsellors were distributed among 484 of the 1542 practices. Three types of counsellor predominated: community psychiatric nurses (187); "practice counsellors" (145); and clinical psychologists (95). Practice characteristics which independently predicted the presence of a counsellor were for community psychiatric nurses four or more partners (odds = 1.72, 95% confidence interval 1.18 to 2.26); for practice counsellors stress clinic (odds = 2.22; 1.83 to 2.61), training practice (odds = 1.70; 1.24 to 2.16), and health region (chi 2 = 55.94; df = 14; p < 0.001); and for clinical psychologists list size of > or = 10,500 (odds = 1.79; 1.09 to 2.49), training practice (odds = 1.78; 1.31 to 2.25), health region (chi 2 = 48.31; df = 14; p < 0.001). 197 counsellors had training in counselling. The qualifications of 85 were unknown to the general practitioner. The principal source of funding was the district health authority for community psychiatric nurses (150) and clinical psychologists (58) and the family health services authority for practice counsellors (76). All counsellors were referred a wide range of problems. CONCLUSIONS: Counselling services are wide-spread in general practice, but a high proportion of counsellors lack qualifications, and many may be referred problems outside their knowledge. PMID- 8435575 TI - Auditing BMJ decision making. PMID- 8435576 TI - Gestational diabetes: a non-entity? AB - Screening for gestational diabetes is commonly recommended despite the absence of a common definition of gestational diabetes. Furthermore, there is no consensus about management or treatment. Those who recommend screening do so largely on the basis of fetal morbidity, which seems to be predominantly "macrosomia"--another term without an agreed definition. The implications of macrosomia in terms of actual morbidity are also not clear. R J Jarrett reviews the history of the subject and concludes that gestational diabetes is simply impaired glucose tolerance temporally associated with pregnancy. Its main importance is as a predictor of subsequent non-insulin dependent diabetes, but it fails the major tests for a condition suitable for a screening programme. PMID- 8435577 TI - William Waldegrave on science policy. Interview by Richard Smith. PMID- 8435578 TI - Laser treatment of portwine stains. PMID- 8435579 TI - The Tomlinson report and postgraduate medical education. AB - The postgraduate hospitals of London grew up in the nineteenth century and offered a unique national specialist service. Since then specialist services have developed in undergraduate hospitals throughout Britain as well as in London, but the postgraduate hospitals have nevertheless preserved their high levels of staffing. Although numbers of medical posts in the provinces have grown, this has not been by redistribution of London posts but merely differential growth. The fact identified by Tomlinson--that Londoners are not receiving the most appropriate clinical care--is in fact the strongest argument for changing postgraduate medical education. Such education needs to be rooted first in clinical care, though Tomlinson underestimates the importance to education of such care being sited in a shared environment with strong scientific activity. PMID- 8435580 TI - Moving ahead--community care in Gwent. PMID- 8435581 TI - ABC of monitoring drug therapy. Making the most of plasma drug concentration measurements. PMID- 8435583 TI - Assessment of students. PMID- 8435582 TI - Treating persistent glue ear in children. PMID- 8435584 TI - Pet birds and lung cancer. PMID- 8435585 TI - Pet birds and lung cancer. PMID- 8435586 TI - Pet birds and lung cancer. PMID- 8435587 TI - Pet birds and lung cancer. PMID- 8435588 TI - Tomlinson report. PMID- 8435589 TI - Use of oral contraceptives by adolescents in Finland. PMID- 8435590 TI - Use of oral contraceptives by adolescents in Finland. PMID- 8435591 TI - Vaccination against H influenzae type b. PMID- 8435592 TI - Health and safety in general practice. PMID- 8435593 TI - Electronic communication. PMID- 8435594 TI - Electronic communication. PMID- 8435595 TI - Asking patients about their treatment. PMID- 8435596 TI - Driving and diabetes. PMID- 8435597 TI - Medical education. PMID- 8435598 TI - Dangers of review articles. PMID- 8435599 TI - Audit and research. PMID- 8435600 TI - Interpreting fluorescein angiograms. PMID- 8435601 TI - Evaluation of two school smoking education programmes under normal classroom conditions. AB - OBJECTIVES: To assess the effectiveness of two school based smoking education projects in delaying onset of smoking behaviour and in improving health knowledge, beliefs, and values. DESIGN: Cluster randomised controlled trial of two projects taught under normal classroom conditions. Schools were allocated to one of four groups to receive the family smoking education project (FSE); the smoking and me project (SAM); both projects in sequence (FSE/SAM); or no intervention at all. SETTING: 39 schools in Wales and England matched for size and catchment profile. SUBJECTS: All first year pupils in the schools were included and were assessed on three occasions (4538 before teaching (1988), 3930 immediately after teaching (1989), 3786 at one year follow up (1990)). MAIN OUTCOME MEASURES: Self reported smoking behaviour (backed by saliva sample) and change in relevant health knowledge, beliefs, and values. RESULTS: No consistent significant differences in smoking behaviour, health knowledge, beliefs, or values were found between the four groups. For never smokers at baseline the rate of remaining never smokers in 1990 was 74% (594/804) in the control group, 65% (455/704) in the FSE group, 70% (440/625) in the SAM group, and 69% (549/791) in the FSE/SAM group (chi 2adj = 6.1, df = 3, p = 0.1). Knowledge about effects of smoking rose in all groups from a mean score of 5.4 in 1988 to 6.4 in 1989 and 6.5 in 1990. CONCLUSIONS: More comprehensive interventions than school health education alone will be needed to reduce teenage smoking. Other measures including further restrictions on access to cigarettes and on the promotion of tobacco products need to be considered. Further research will be needed to develop effective school based health education projects, which should be formally field tested under normal conditions before widespread dissemination. PMID- 8435602 TI - Fatal hepatic decompensation associated with interferon alfa. European concerted action on viral hepatitis (Eurohep). PMID- 8435603 TI - Acute eosinophilic pneumonia induced by inhaled pentamidine isethionate. PMID- 8435605 TI - Visual failure and optic atrophy associated with chlorambucil therapy. PMID- 8435604 TI - Hypersensitivity to dexamethasone. PMID- 8435606 TI - Influence of Royal College of Radiologists' guidelines on referral from general practice. Royal College of Radiologists Working Party. AB - OBJECTIVE: To measure the effect on general practitioner referrals for radiography of introducing guidelines of good practice together with monitoring and peer review. DESIGN: Collection of referral data during 1 January 1989 to 31 December 1990. Guidelines were introduced on 1 January 1990. SETTING: Open access radiology services provided by one non-teaching district in England. SUBJECTS: 144614 registered patients from 22 practices. MAIN OUTCOME MEASURES: Number of referrals per 1000 registered patients for radiography of the chest, skull, spine, abdomen, limbs, and joints and for barium investigation and excretion urography. RESULTS: Overall referrals fell from 88.4/1000 registered patients to 77.2/1000 after the guidelines were introduced. The commonest reasons for referral were for examination of the chest, spine, and limbs and joints and referrals for these fell by 9.4%, 17.5%, and 13.5% respectively. Referrals for skull radiography fell by 30% (from 241 to 168). CONCLUSIONS: By helping general practitioners to be more selective in their use of diagnostic radiology, the guidelines reduced the rate of referral and thus patients' exposure to radiation. PMID- 8435607 TI - Empowering GPs as purchasers. AB - FHSAs have defined their role in purchasing primary care FHSAs have also found themselves intermediaries between district health authorities and general practitioners All of the purchasing authorities recognise the need to educate general practitioners on how to use their influence in the purchasing process General practitioners should be involved in the purchasing process as they purchase the bulk of health care; are the first point of contact for the users of the health service; need to have input on what is purchased; and need to be able to manage the changes resulting from the shift in the balance of power towards primary care The involvement of general practitioners in the purchasing process at present varies considerably among health authorities. Several district health authorities have developed models of purchasing that enable different levels of involvement PMID- 8435608 TI - Phenylketonuria due to phenylalanine hydroxylase deficiency: an unfolding story. Medical Research Council Working Party on Phenylketonuria. AB - Efficient neonatal screening for phenylketonuria and the availability of complex diets for lifelong use have virtually eliminated severe mental handicap from the disease. Nevertheless, there remains a high risk of fetal damage in offspring of women with the disease, and the possibility that the diets themselves may be harmful cannot be excluded. Search for a preventive treatment for the disease has been greatly aided by advances in molecular genetics. For example, in mice modified liver cells have been implanted, which have not only corrected the phenylalanine defect but have remained healthy for the normal life span of the animal. Overall, however, prevention and treatment have not progressed as quickly as was hoped, and research and development must be pursued vigorously to take account of contemporary perceptions of the disorder. PMID- 8435609 TI - Australian court decision on passive smoking upheld on appeal. PMID- 8435610 TI - Alternative allergy and the General Medical Council. AB - In July 1992 Dr Keith Mumby, a clinical ecologist, appeared before the professional conduct committee of the General Medical Council on five charges to do with his practice of clinical ecology. He was found guilty of two of the charges--touting for publicity and failing to give a patient adequate medical attention--and admonished. The GMC failed, however, to address the issue of the nature of Mumby's treatments--clinical ecology itself. This is based on the idea that some patients are unusually susceptible to their environment, the diagnosis and treatment are based on an unstandardised provocation-neutralisation test. A variety of medical bodies have failed to find scientific foundation for the technique. The GMC's policy on advertising services to patients is inconsistent, and in this case it has shown a regrettable reluctance to deal with the issue of treatments that are not scientifically validated. PMID- 8435612 TI - Managing change: the human aspects of the NHS. AB - Whatever ministers actually decide about London following the Tomlinson report, the changes are likely to be large-scale and affect many staff and patients. Therefore how well those changes are handled becomes crucial to their success. The NHS has much to learn from other industries and organisations that have been through similar changes. Firstly, there needs to be an overall strategy for the change, rather than individual units trying to manage their own parts of it in an ad hoc way. Secondly, how well those made redundant are treated is an important factor in maintaining the morale of those who stay behind. For those affected by changes the NHS needs to provide full information, imagination, time, emotional and practical support, and money. Though decisions need to be made quickly, their implementation should take as much time as is necessary. PMID- 8435611 TI - Health of nations: lessons from Victoria, Australia. AB - In its white paper The Health of the Nation the government has announced its intention to give more priority to preventive health care. Two examples from Victoria, Australia, show how coordinated legislative and voluntary sector action can have a substantial impact on public behaviour. The introduction and enforcement of strict drink-driving laws and speed limits backed up by forceful television advertisements produced a large reduction in deaths from road traffic accidents, the death rate in relation to the number of vehicles in 1991 being among the lowest in the world. Smoking has also declined in parallel with a phased ban on advertising and use of taxes from tobacco sales to replace tobacco sponsorship of sports and arts and fund health promotion. PMID- 8435613 TI - Reaching out--community care in Bassetlaw. PMID- 8435614 TI - Obstructive lymphatic filariasis. PMID- 8435615 TI - Infant mortality and army families. PMID- 8435616 TI - Infant mortality and army families. PMID- 8435617 TI - Infant mortality and army families. PMID- 8435618 TI - Practice reports. PMID- 8435619 TI - Practice reports. PMID- 8435620 TI - Fundholding practices get preference. PMID- 8435621 TI - Fundholding practices get preference. PMID- 8435622 TI - Practice reports. PMID- 8435623 TI - Confounding in epidemiological studies. PMID- 8435624 TI - Consultant episodes. PMID- 8435625 TI - Letting vegetative patients die. PMID- 8435626 TI - Letting vegetative patients die. PMID- 8435627 TI - Hyponatraemia associated with paroxetine. PMID- 8435628 TI - Screening for neuroblastoma. PMID- 8435629 TI - Botulinum toxin for hemifacial spasm. PMID- 8435630 TI - Lung cancer and breast cancer in women. PMID- 8435631 TI - Organ donation. PMID- 8435632 TI - Organ donation. PMID- 8435633 TI - Cardiovascular disease in developing countries. PMID- 8435634 TI - Assisted conception: cumulative effectiveness. PMID- 8435635 TI - Pregnancy and ionising radiation. PMID- 8435636 TI - "Economic relevance" in pharmacoeconomic studies. PMID- 8435638 TI - Health promotion in general practice. PMID- 8435639 TI - Specialist training. PMID- 8435637 TI - Maintaining excellence. PMID- 8435640 TI - Specialist training. PMID- 8435641 TI - How go the NHS reforms? PMID- 8435642 TI - How useful is activated charcoal? PMID- 8435643 TI - The cervical spine in rheumatoid arthritis. PMID- 8435644 TI - Health promotion and children and teenagers. PMID- 8435645 TI - Drugs, secrecy, and society. PMID- 8435646 TI - GMC in the dock again. PMID- 8435647 TI - HIV prevalence: anonymous surveys yield more evidence. PMID- 8435648 TI - Cancer in Cumbria and in the vicinity of the Sellafield nuclear installation, 1963-90. AB - OBJECTIVE: To reappraise the epidemiological findings reported by the Black Advisory Group concerning a possible excess of malignant disease, particularly of childhood acute lymphoid leukaemia and non-Hodgkin lymphomas, in the vicinity of the Sellafield nuclear installation, and to determine whether any excess of malignant disease had occurred among people aged 0-24 years in the area in the years after the Black report--that is, from 1984 to 1990. DESIGN: Calculation of incidence of cancer using data from population based cancer registries and special surveys. SETTING: England and Wales; county of Cumbria; county districts Allerdale and Copeland within Cumbria; Seascale ward within Copeland. SUBJECTS: All residents under the age of 75 years in the above areas, but with particular reference to those aged 0-24 years. MAIN OUTCOME MEASURES: Numbers of cases and incidence particularly of lymphoid leukaemia and non-Hodgkin lymphomas in those aged 0-24 years, but including other cancers and age groups. RESULTS: Previous reports of an increased incidence of cancer, especially of leukaemia, among those aged 0-24 years in Seascale during the period up to and including 1983 are confirmed. During 1984-90 there was an excess of total cancer among those aged 0 24 years. This was based on four cases including two cases of non-Hodgkin lymphoma but none of leukaemia. There was an increased, but nonsignificant, incidence of other cancers, based on two cases (one pinealoma and one Hodgkin's disease) occurring among those aged 15-24 years during 1984-90. This was not observed in the younger age group or in previous years. For the immediately surrounding area--that is, the county districts of Allerdale and Copeland excluding Seascale and in the remainder of Cumbria--there was no evidence of an increased incidence of cancer among those aged 0-24 years in either period. CONCLUSIONS: During 1963-83 and 1984-90 the incidence of malignant disease, particularly lymphoid leukaemia and non-Hodgkin lymphomas, in young people aged 0 24 in Seascale was higher than would be expected on the basis of either national rates or those for the surrounding areas. Although this increased risk is unlikely to be due to chance, the reasons for it are still unknown. PMID- 8435649 TI - Evidence of unmet need in the care of severely physically disabled adults. AB - OBJECTIVE: To identify unmet needs in the care of severely disabled people aged 16-64. DESIGN: Detailed personal interview and physical assessment of physically disabled adults; personal or telephone interview with carers. SETTING: Somerset Health District. SUBJECTS: 181 severely disabled adults and their carers. MAIN OUTCOME MEASURES: Independence in activities of daily living; identity of requirements for assessing communication disorders; appropriate provision of services and allowances. RESULTS: 53 (29.3%) of the 181 disabled subjects had unmet needs for aids to allow independence in activities of daily living-namely, 43% of subjects (41/95) with progressive disorders and 14% of subjects (12/86) with non-progressive disorders. The prevalence of unmet need was higher among subjects whose sole regular professional contact was with health services personnel (48 (40.3%) of 119 subjects). Only 18 (31.6%) of the 57 subjects with communication disorders had ever been assessed by a speech therapist. CONCLUSIONS: This study shows that the needs of severely physically disabled adults in the community--especially those with progressive disorders--are being monitored inadequately by health professionals. PMID- 8435650 TI - Long term follow up of severely ill patients who underwent urgent cardiac transplantation. AB - OBJECTIVE: To assess long term survival (> 5 years) and quality of life in severely ill patients referred for urgent cardiac transplantation. SETTING: Tertiary referral centres: before transplantation at the National Heart Hospital (late 1984 to end 1986); after transplantation at Harefield Hospital. SUBJECTS: Eighteen patients (15 men; three women) who had required intensive support in hospital before cardiac transplantation and were alive at short term follow up. INTERVENTIONS: Intravenous infusions of cardiac drugs (mean 2.2 infusions), intravenous diuretics (17 patients), and many other drugs before transplantation. Intra-aortic balloon counterpulsation (four patients), temporary pacing (two), and resuscitation from cardiac arrest (three). Patients had specialised nursing care on a medical intensive care unit in almost every case. MAIN OUTCOME MEASURES: Long term survival in patients after urgent cardiac transplantation and perceived quality of life. RESULTS: Of 18 patients who were alive at short term follow up (mean (range) 19.4 (10-33) months), 14 were still alive in 1992 (69 (61 83) months). Ten still worked full time, and 11 reported no restrictions in their daily activities. Three of four patients who died in the intervening period survived > 5 years after transplantation. Overall, 17 of 18 patients survived at least 5 years. CONCLUSIONS: In severely ill patients who undergo urgent cardiac transplantation and survive in the short term, long term (5-7 year) survival and quality of life seem good. PMID- 8435651 TI - Multifocal inner choroiditis. AB - Young, moderately myopic women presenting with typical signs of ocular histoplasmosis (OHS) but negative serology or skin tests were delimited in 1984 as a new entity of "punctate inner choroidopathy". On the basis of observations in 17 patients combined with similar cases reported in the literature, the following hypothesis is proposed herein. Myopia, young age and female sex are general high-risk factors for the development of focal choroidopathy. A hypothesis is presented to explain this accumulation. Women have a significantly higher risk of developing bacteremia before the age of 50 years than do men. The attenuated choroidal vessels in myopia might elevate the risk for infectious thrombosis in the choriocapillary layer. When combined, these risk factors could significantly lower the infectious threshold, leading to infections outside areas endemic for particularly virulent agents. The more general term multifocal inner choroiditis, proposed by Krill in 1968, should be maintained to emphasise the multifactorial genesis of this disease. Patients go to an ophthalmologist when secondary complications such as subretinal neovascular membranes have developed; this makes the search for causes of the primary infection difficult, if not impossible. Further studies carried out in collaboration with gynaecologists and other subspecialists are necessary to challenge this hypothesis and to evaluate the possibilities of preventing multifocal inner choroiditis. PMID- 8435652 TI - Vitrectomy in multifocal chorioretinitis. AB - In nine patients suffering from multifocal chorioretinitis with panuveitis, we obtained no impressive therapeutic benefit from vitrectomy. Seven women and two men ranging in age from 63 to 86 years underwent pars plana vitrectomy at 3-28 months after the first signs of uveitis had appeared. Previous medical treatment had always been unsuccessful. Vitrectomy was performed in one eye of eight patients and in both eyes of one patient. In addition, in two patients a cataract was removed by phacoemulsification and an intraocular lens was implanted. A visual improvement of one or two lines was achieved postoperatively in most cases, but the visual acuity decreased to preoperative values or less within 6 months. The surgical treatment showed no obvious effect on the intensity or frequency of uveitis relapse. In all cases, vitrectomy specimens were serologically negative for herpes-group viruses. Histologically, no malignancy was detectable. Immunohistochemistry studies revealed that a large number of the vitreous cells bore T-lymphocyte markers (mostly CD2-, CD3-, and CD4-positive); about one-third of the vitreous cells were macrophages, and B-lymphocytes were only rarely detected. In conclusion, pars plana vitrectomy in multifocal chorioretinitis achieved no positive long-term result. There was no diagnostic hint as to whether the cause of the uveitis might have been of a viral, malignant, or autoimmune origin. Therefore, multifocal chorioretinitis remains poorly understood in terms of its etiology and adequate treatment. PMID- 8435653 TI - Vitrectomy and fluid/silicone oil exchange for giant retinal tears: 10-year follow-up. AB - A total of 39 eyes of 39 patients, previously reviewed 5 years after vitrectomy and fluid/silicone oil exchange for giant retinal tears, were reexamined after 10 years. The retina remained attached in 30 eyes (77%), and in no case had redetachment occurred in the interval between 5 and 10 years after surgery. In all, 3 groups of eyes were identified, 20 eyes with attached retinas and visual acuities of 6/60 or better (group I), 10 with attached retinas and vision of less than 6/60 (group II) and 9 in which the retina was detached (group III). Eyes in group I were found to be stable, with future improvement anticipated in some cases with cataracts. A majority of group II eyes were deteriorating due to glaucoma and keratopathy. Failure in group III was due to proliferative vitreoretinopathy in all except one instance. Measures aimed at reducing the incidence of epiretinal membrane proliferation, glaucoma and keratopathy are recommended to improve long-term results in the treatment of retinal detachments complicated by giant retinal tears. These include the use of safer methods of retinopexy, preservation of the lens when possible, early removal of silicone oil and a reduction in the use of scleral buckles. PMID- 8435654 TI - Ophthalmological follow-up of diabetic patients after kidney transplantation. AB - Visual acuity (VA) and changes in diabetic retinopathy after kidney transplantation were prospectively evaluated in 29 patients with type 1 diabetes. At the time of transplantation, 9 patients (31%) had background retinopathy (RP) and 20 patients (69%) had proliferative RP in one eye or both eyes. During the follow-up period of 0.5-4 years (median, 3.0 years), background RP remained stable in 13 of 22 eyes (59.1%), improved in 6 eyes (27.3%) and changed to proliferative RP in 3 eyes (13.6%). Of the 26 eyes with proliferative RP, proliferative changes decreased in 6 (23.1%) and increased in 4 (15.4%). Initially 11 eyes were blind (VA less than counting fingers at 1 m), and in 1 of them the VA improved after vitrectomy. In 42 of the remaining 47 eyes (89.4%) the VA remained unchanged (within 2 lines better or worse), in 4 eyes (8.5%) it improved and in 1 eye (2.1%) it deteriorated. Five patients died during the follow-up period. These results indicate that in most diabetic patients, retinopathy remains stable or improves after kidney transplantation, but regular ophthalmological follow-up is important for the discovery of eyes in which further treatment is indicated. PMID- 8435655 TI - Vision with bifocal intraocular lenses. AB - The laboratory and clinical results of tests of different bifocal intraocular lenses (BIOLs) are compared. Included are two-zone refractive BIOLs with a central near zone and an annular distance zone (group 1); three-zone refractive BIOLs with a central distance zone, an annular near zone, and a peripheral distance zone (group 2); diffractive BIOLs (group 3); multizone refractive BIOLs (group 4); and other BIOLs (group 5). All BIOLs cause a significant loss of image contrast and acuity at low contrast. The incidence of visual side effects (e.g., halos, glare) varies but is significantly higher than that obtained with monofocal IOLs. On the other hand, BIOLs provide a depth of focus of 3-4 D as compared with only 1.5 D for monofocal IOLs. In group 1, distance vision is reduced in bright light, which limits the clinical use of these BIOLs. In group 2, distance vision is better than near vision. Thus, a temporary near add is required in some cases. In group 3, distance and near vision are similar, but the incidence of visual side effects is higher than that in group 2. Only BIOLs of groups 2 and 3 can be recommended for clinical use in selected patients. Not enough data are currently available on the other groups. Patient selection is the most critical factor for BIOLs. Ideal patients are relatively young and active, are highly motivated, show no ocular pathology, and have a normal pupil, an axial length of 22-24.5 mm, and a corneal astigmatism of less than 1 D. Reduced image contrast, mainly at near focus, and visual side effects must be acceptable. Bilateral implantation yields the best results. A monofocal fellow eye is a definite contraindication. In summary, BIOLs cannot replace monofocal IOLs. However, they provide a valuable alternative in selected patients. PMID- 8435656 TI - Limbus-parallel keratotomies and compression sutures in excessive astigmatism after penetrating keratoplasty. AB - From 1986 to 1991, among 980 penetrating keratoplasties, all 22 patients were studied retrospectively who had undergone 28 refractive procedures because of high corneal astigmatism after penetrating keratoplasty. In 8 procedures, only relaxing incisions were made, and in 20 procedures, additional compression sutures were placed at 90 degrees to the former. In 7 cases the relaxing incisions were located on the patient's peripheral cornea and in 21 cases, inside the graft margin. The absolute preoperative corneal astigmatism was 7.25-20.0 D (mean, 11.5 +/- 3.1 D). Immediately after surgery it was 0-14.0 D (mean, 7.0 +/- 3.6 D). The vector-corrected astigmatism immediately after surgery was 1.0-28.9 D (mean, 13.2 +/- 7.8 D). After a mean follow-up of 20.6 months, the mean residual astigmatism was 1.0 +/- 11.25 D (mean, 5.4-2.5 D). The mean postoperative vector corrected astigmatism was 0-19.3 D (mean, 9.1 +/- 4.6 D). The best-corrected preoperative visual acuity was 0.12-0.9 (mean, 0.4), the best postoperative visual acuity was 0.3-1.2 (mean, 0.6). The approach described may reduce disturbing postkeratoplasty astigmatism--although the predictability remains unsatisfactory. PMID- 8435657 TI - Pseudoexfoliative material in the eyelid skin of pseudoexfoliation-suspect patients: a clinico-histopathological correlation. AB - The pseudoexfoliation (PSX) syndrome has recently been suggested to represent the intraocular manifestation of a systemic disorder. In the present study, we examined the correlation between the extraocular occurrence of PSX material in eyelid skin and clinical indications of early stages of PSX syndrome using transmission and immunoelectron microscopy. Typical PSX aggregates were demonstrated in 7 of the eyelid-skin biopsy specimens taken from 12 patients who had been categorized as "PSX suspects" on the basis of certain clinical signs related to loss and dispersion of melanin from the iris pigment epithelium and to iris stromal atrophy but showed no clinical evidence of PSX syndrome in either eye. Another 3 lid specimens obtained from PSX suspects exhibited signs of atypical PSX fibrillopathy. The PSX deposits revealed immunolabeling for heparan and chondroitin sulfate proteoglycan, entactin/nidogen, elastin, amyloid P, and vitronectin. These findings suggest that certain clinical signs indicating early PSX syndrome obviously correlate with the extraocular occurrence of PSX material before its clinically visible appearance on the surfaces of the anterior and posterior chambers. PMID- 8435658 TI - Orbital pseudotumor presenting as acute glaucoma with choroidal and retinal detachment. AB - A 68-year-old woman presented with acute visual loss, elevated intraocular pressure (IOP), and a flat anterior chamber combined with retinal and choroidal detachment. The diagnosis of orbital pseudotumor was based on the patient's poor response to conventional therapy and on computerized tomography and ultrasound findings. After treatment with oral corticosteroids, the inflammatory process, elevated IOP, and choroidal and retinal detachment resolved. PMID- 8435659 TI - Lipemia retinalis. PMID- 8435660 TI - Donor leucocyte infusions after chemotherapy for patients relapsing with acute leukaemia following allogeneic BMT. AB - Four patients with acute myeloid leukaemia relapsed within 6 months of allogeneic BMT. Three patients were treated with cytosine arabinoside and amsacrine while the fourth received no chemotherapy. All patients received infusions of leucocytes obtained by repeated leukapheresis from the original bone marrow donor. Three patients developed GVHD requiring immunosuppressive therapy. One of these achieved a complete remission which has been sustained for more than 1 year with 100% donor haematopoiesis. The other patients died with persistent leukaemia 45-134 days after the infusions of donor cells. We conclude that the addition of marrow donor leucocytes to salvage chemotherapy may produce durable remissions in patients with acute myeloid leukaemia relapsing after BMT and that this may be due to a graft-versus-leukaemia effect. PMID- 8435661 TI - Comparison of engraftment and acute GVHD in patients undergoing cryopreserved or fresh allogeneic BMT. AB - Coordination of marrow donation for allogeneic BMT is a common logistical problem. The use of cryopreserved donor marrow would facilitate scheduling and avoid potential problems due to donor employment, injury, infection or death. We analysed results of 10 matched related BMTs performed with cryopreserved donor marrow and compared them with 33 matched related BMTs using fresh bone marrow over a 4 year period. No difference in time to engraftment of granulocytes and platelets or transfusion requirements were demonstrated for the two groups. However, there was less GVHD in patients who received cryopreserved donor marrow (chi 2, p = 0.03; Fisher's exact test (two-sided) p = 0.067) despite comparable risk factors. The reason for this difference is unclear. Our results indicate that the use of cryopreserved bone marrow for allogeneic BMT patients is at least equivalent to the use of fresh bone marrow. A prospective randomized trial is needed to determine if a true difference exists in the incidence or severity of acute GVHD and to determine if recurrence rate is different between the two groups. PMID- 8435662 TI - T cell and NK cell mediated graft-versus-leukaemia reactivity following donor buffy coat transfusion to treat relapse after marrow transplantation for chronic myeloid leukaemia. AB - Two patients with chronic myeloid leukaemia in cytogenetic relapse following T lymphocyte-depleted BMT were treated with transfusions of donor buffy coat leucocytes. In both patients the marrow reverted to a completely normal karyotype and was negative for the BCR-ABL fusion gene transcript by polymerase chain reaction analysis. Before buffy coat transfusion the cytotoxic T lymphocyte precursor frequency against pre-BMT patient leukaemia cells (Lk-CTLP) was lower than that against pre-BMT patient PHA-transformed lymphocytes (Ly-CTLP) in both cases. At 2 weeks (case 1) and 8 weeks (case 2) after transfusion this ratio inverted so that Lk-CTLP predominated. Natural killer (NK) function fell initially and then recovered to exceed pre-transfusion values prior to normalization of the bone marrow karyotype. These changes in cytotoxic T lymphocytes and NK cells following donor buffy coat transfusions for patients with relapsed chronic myeloid leukaemia after marrow transplantation support the concept of a graft-versus-leukaemia effect mediated by both MHC restricted and non-restricted pathways. PMID- 8435663 TI - Treatment of multiple myeloma with intensive chemotherapy followed by autologous BMT using marrow purged with 4-hydroperoxycyclophosphamide. AB - In August 1988 we began a program in which multiple myeloma patients achieving < or = 10% marrow plasma cells and > or = 50% reduction in paraprotein levels after the VAD (vincristine, doxorubicin, dexamethasone) regimen underwent bone marrow harvest, ex vivo marrow purging with 4-hydroperoxycyclophosphamide (4-HC) and marrow cryopreservation. Conditioning with a regimen of high-dose busulfan (total dose 16 mg/kg), cyclophosphamide (120 mg/kg) and melphalan (90 mg/m2) (BU + CY + MEL) followed by autologous BMT was then carried out. Seventeen of the 24 patients who received VAD (71%, 95% confidence interval [CI] 49 to 87%) were eligible for bone marrow harvest. One patient was not harvested because of non medical reasons; two patients who underwent marrow harvest had gross plasmacytosis present in biopsies performed intraoperatively and did not undergo BMT. Fourteen patients (58%, 95% CI 37 to 78%) received BU + CY + MEL and 4-HC purged autologous BMT. The median time to recovery of 0.5 x 10(9)/l neutrophils was 19 days (range 14 to 26) while the last platelet transfusion was given on a median of day 32 (range 10 to 46) post-BMT in the evaluable patients. The major non-hematologic toxicity was hepatic; two patients in complete remission died of hepatic veno-occlusive disease. Another patient succumbed to fungal infection despite neutrophil recovery. The remaining 11 patients achieved responses (complete in six and partial in five) associated with a normal performance status.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8435664 TI - A novel approach to immunomodulation of frozen human bone marrow with interleukin 2 for clinical application. AB - Interleukin-2 (IL-2) activation of fresh or frozen bone marrow (BM) in vitro generates killer cells with potent anti-tumor effect both in vitro and in vivo. The IL-2-activated BM (ABM) retains the capacity to reconstitute the hematopoietic system in an autologous bone marrow transplantation (ABMT) setting. The killer cells lose their cytotoxicity if the ABM undergoes the procedures of freezing and thawing. Therefore, for clinical application, the ABM has to be generated after thawing a frozen stock of BM before ABMT. The thawed BM cells are fragile and may undergo lysis, resulting in clump formation and cell loss. The frozen autograft also contains components of cryoprotectant mixture whose effects on the generation of ABM have not been defined. The present studies have been carried out to optimize a technique of handling the frozen BM for immunomodulation with IL-2 for 24 h at 37 degrees C prior to ABMT, with minimal loss of cells. IL-2-activation of BM was carried out in bags containing serum free medium which were designed to permit gaseous exchange. Addition of deoxyribonuclease (DNAse) (100 micrograms/ml of BM concentrate) immediately after thawing and the presence of heparin (20 units/ml) in the medium completely abrogated immediate or delayed clumping of cells. The presence of DNAse and/or heparin during in vitro culture did not affect the cell viability, cytotoxicity against tumor cells or the progenitor cell activity of the ABM; all these functions were well maintained even when BM was placed in culture immediately after thawing (without washing). There was no microbial contamination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8435665 TI - Fatal eosinophilia myalgia syndrome in a marrow transplant patient attributed to total parenteral nutrition with a solution containing tryptophan. AB - A 16-year-old white male with acute biphenotypic leukemia developed evidence of the eosinophilia myalgia syndrome associated with total parenteral nutritional support with solutions containing tryptophan, which were given during his initial induction chemotherapy and also after autologous marrow transplantation. He developed pronounced eosinophilia and a vasculitic skin rash, myalgias of the abdomen, upper trunk, and neck, and died of respiratory distress with no evidence of an infectious etiology. Autopsy revealed diffuse vasculitis involving the heart, lungs, kidneys, testes, spleen, liver, skin, gut wall and marrow with neuritis of gut wall nerves and ganglia. Thus, the eosinophilia myalgia syndrome can be associated with parenteral tryptophan administration. PMID- 8435666 TI - Polymerase chain reaction: a method for monitoring tumor cell purge by long-term culture in BCR/ABL positive acute lymphoblastic leukemia. AB - We report the successful purging of leukemia cells bearing the Philadelphia chromosome and BCR/ABL transcripts by long-term marrow culture (LTC), and subsequent grafting of the purged marrow in a case of refractory acute lymphoblastic leukemia. The efficiency of the purge was evaluated by polymerase chain reaction (PCR) for BCR/ABL transcripts. In two LTCs initiated in the blastic stage, we demonstrated the selective effect of three culture media (serum dependent, serum-free (SF) supplemented or not with IL3 and GM-CSF) on the proliferative potential of normal hematopoietic (CFU-GM/BFU-E) and leukemic progenitors (CFU-ALL). BCR/ABL positive cells disappeared after 3 to 4 weeks of culture. The addition of IL3 and GM-CSF to the SF medium enhanced the growth of CFU-GM/BFU-E and shortened the purging period. We therefore carried out a LTC in the presence of IL3 and GM-CSF with marrow harvested in morphological remission. BCR/ABL positivity was detected at the outset, although no leukemia cells could be identified. The BCR/ABL was no longer found by PCR in the 7 and 14 day LTCs. The patient, consolidated by high dose polychemotherapy and total body irradiation, was infused with the 14 day LTC. This study indicates that PCR is a useful and sensitive technique for monitoring tumor cell reduction after LTC prior to autografting. PMID- 8435667 TI - Recovery from diabetes insipidus associated with AML after a BMT conditioning regimen including busulfan. AB - We describe a patient who, at the onset of acute myelomonocytic leukemia, presented with marked polyuria, polydipsia and laboratory findings consistent with diabetes insipidus (DI). He was treated with vasopressin (DDAVP) with a good response and concurrently induced with daunorubicin and conventional doses of cytosine arabinoside. CR was achieved. The vasopressin requirement decreased progressively, but the patient remained DDAVP-dependent after consolidation treatment. He underwent allogeneic BMT, conditioned with busulfan and cyclophosphamide. By day 15 after BMT vasopressin was no longer required and at a follow-up of 9 months the patient has no evidence of DI. In the absence of specific findings, we think it possible that he had leukemic microinfiltration of the hypothalamic-pituitary area. The drugs used for conditioning may have eradicated CNS disease. PMID- 8435668 TI - Mixed chimaerism; detection and significance following BMT. AB - Residual recipient haematopoietic cells may coexist with donor haemopoietic tissue following BMT. This is known as mixed chimaerism. The incidence of mixed chimaerism varies with the sensitivity of the detection system used; DNA based methodologies are the most sensitive. The influence of mixed chimaerism on leukaemia relapse and graft rejection is unclear. The lineages in which mixed chimaerism occurs may affect outcome. PMID- 8435669 TI - Comparison of chromosome studies on PHA-stimulated blood and unstimulated bone marrow cells in recipients of lymphocyte depleted grafts using counterflow centrifugation. AB - We performed chromosome studies on 121 paired samples of phytohaemagglutinin stimulated blood and unstimulated bone marrow cells from 57 recipients of lymphocyte depleted grafts using counterflow centrifugation. The paired samples were drawn simultaneously 6-108 months after transplantation. The incidence of mixed chimaerism was higher in blood than in bone marrow cells, both in patients who relapsed and in patients in continuous complete remission. The higher number of mixed lymphoid chimaeras is caused by autologous T lymphocytes which have survived the conditioning regimen and/or by donor lymphocytes which persisted after disappearance of the marrow graft. The type of blood and bone marrow chimaerism had no significant impact on the incidence of chronic GVHD but the overall incidence of chronic GVHD was too low to allow an accurate assessment. Cytogenetic analysis is a useful method for assessing chimaerism after bone marrow transplantation. Apart from its limited sensitivity for the demonstration of a minor cell population, discrepancies between chromosome studies of blood cells (lymphoid chimaerism) and bone marrow cells (myeloid/erythroid chimaerism) have to be taken into consideration. PMID- 8435670 TI - Male breast cancer. AB - The most important epidemiological, aetiological, diagnostic and therapeutic problems related to male breast cancer are reviewed. Early diagnosis is important in order to achieve optimal results, which can be similar to those following the treatment of female breast cancer. PMID- 8435671 TI - Psychological and social problems of Parkinson's disease. AB - Idiopathic Parkinson's disease is a common neurodegnerative disorder which is frequently associated with psychological, psychiatric and social problems. The association of psychological symptoms and a neurological disorder that has clear neuropathology provides researchers with the exciting prospect of finding biological models for common behavioural states. PMID- 8435672 TI - Digital chest radiography. AB - Apart from projectional and plain radiographs, all images in a radiology department are obtained in a digital format and handled by computers. It is now technically possible to acquire a digital chest radiograph without the use of conventional film. There are advantages in the image processing of digital chest radiographs but the cost remains a compelling obstacle. PMID- 8435673 TI - Centoxin. AB - Centoxin is one of a new group of immunotherapeutic agents manufactured from 'humanized' antibodies produced using monoclonal antibody technology. It is indicated in the management of patients with Gram-negative septicaemia; its introduction represents a new approach to treatment in these patients (Luce, 1987). PMID- 8435674 TI - Asthma in childhood. AB - The prevalence of wheezy illness in children is increasing, along with the number of children diagnosed as having asthma. If physicians are to provide the most effective treatment for these patients, they need to be fully aware of advances in our understanding of the pathophysiology of asthma and of the new and improved treatments that these have brought about. PMID- 8435675 TI - All doctors need plastic surgery. PMID- 8435676 TI - Optimizing the benefits of cardiomyoplasty. PMID- 8435677 TI - Optimizing the benefits of cardiomyoplasty. PMID- 8435678 TI - Why pathologists need medical defence unions. PMID- 8435679 TI - Vaccination: the next 10 years. PMID- 8435681 TI - The National Blood Authority. PMID- 8435680 TI - Acoustic neuroma: triumph and disaster. PMID- 8435682 TI - Magnetic resonance imaging of the heart. AB - Magnetic resonance imaging of the heart has an established role in the assessment of congenital heart disease, the aorta, the pericardium and cardiac tumours. It supplements the information provided by echocardiography and Doppler ultrasound scanning and provides reliable studies of blood flow. Recent developments include myocardial perfusion imaging using real-time techniques and progress towards non invasive coronary angiography. PMID- 8435683 TI - Evolutionary biology and psychiatry. PMID- 8435684 TI - Psychiatry is more than a science. AB - Some loosely framed hypotheses may be stated. (a) Psychiatry depends on science and considerably more besides. (b) Consideration of the clinical methods of psychiatry enables us to characterise six axioms of fundamental importance to the subject which are primary features of human experience, not derived from any theory, ethically neutral and in principle independent of culture. (c) These axioms do not belong to the world of science, in that they are unlikely ever to be fully comprehended by scientific methods. Although they can to a limited extent be studied scientifically, in essence they belong to that part of the world of human experience which is not amenable to scientific study. They are of critical importance to psychiatry, and may be of relevance to all clinical specialties. (d) Psychoanalytic theory and its derivatives contain much that has a bearing on these axioms. Insofar as there is a connection, the theory derives from the axioms rather than vice versa. (e) In their concern with the uniqueness of the individual, his/her inner feelings and thoughts, consciousness of self, empathy and transactions with others, the axioms have common ground with the group of disciplines known as the humanities. (f) Their relationship with the humanities is not such that one can at present identify specific advantages to the psychiatrist (or to the mentally ill person) that might accrue from studying particular topics in literature, art and music. (g) Among the humanities, the one subject that may prove to have relevance to appropriate theory and competent practice is philosophy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8435685 TI - Stressful life events and schizophrenia. I: A review of the research. AB - Empirical research concerning the relationship between life event stressors and schizophrenia is critically reviewed. In accordance with the view that patients suffering from schizophrenia are vulnerable to stress, there is evidence of a relationship between stressors and variation in severity of symptoms over time. There is less indication that schizophrenic patients have had higher levels of stressors than the general population or than patients suffering from other psychiatric disorders. These findings are consistent with vulnerability-stress models of the development of schizophrenia. PMID- 8435686 TI - Stressful life events and schizophrenia. II: Conceptual and methodological issues. AB - Research on the relationship between stress and schizophrenia is fraught with conceptual and methodological problems. These problems include issues related to the nature and measurement of stress, the likelihood of reciprocal influences between stress and symptoms, and the adequate assessment of symptoms. Several recommendations are made regarding future research in this area. These include using multiple and broadly based measures of different types of stressors and symptoms, greater use of truly prospective research designs, and the evaluation of the effects of interventions specifically designed to reduce stress in patients who suffer from schizophrenia. PMID- 8435687 TI - How long should the elderly take antidepressants? A double-blind placebo controlled study of continuation/prophylaxis therapy with dothiepin. Old Age Depression Interest Group. AB - Of 219 elderly patients with a major depressive disorder (meeting RDC), 69 recovered sufficiently and consented to enter a two-year double-blind placebo controlled trial of dothiepin. Survival analysis revealed that dothiepin reduced the relative risk of relapse by two and a half times. Past but not current serious physical illness was also associated with a favourable outcome, whereas a prolonged index depressive illness trebled the relative risk of relapse. In the light of previous research on prognosis it is suggested that elderly persons who recover from a major depressive illness should continue with antidepressant medication for at least two years, if not indefinitely. PMID- 8435688 TI - Is the mechanism of prefrontal hypofunction in depression the same as in schizophrenia? Regional cerebral blood flow during cognitive activation. AB - To test the hypothesis that depressed and schizophrenic patients have a common pathophysiological mechanism for hypofunction of the prefrontal cortex ('hypofrontality'), we measured regional cortical blood flow (rCBF) in ten depressed patients, ten patients with schizophrenia, and 20 age- and sex-matched normal controls. Blood flow was measured during three different cognitive conditions: a resting state, a simple number-matching sensorimotor control task, and the Wisconsin Card Sorting test (WCS). The schizophrenic patients had lower prefrontal rCBF during the WCS. There were no differences in global or regional flow between the depressed patients and the normal subjects during any testing condition. Analysis of rCBF lateralisation showed that during the WCS normal subjects had relatively more left parietal blood flow than depressed patients, who had more right parietal blood flow. Since the testing condition that has most consistently revealed hypofrontality in schizophrenia (i.e. the WCS) was not associated with abnormal rCBF in the depressed patients, these data suggest that the pathophysiological mechanisms underlying prefrontal hypofunction in depression and schizophrenia are different. PMID- 8435689 TI - Impulsivity and eating disorders. AB - Sixty-seven patients with bulimia nervosa and 29 patients with anorexia nervosa completed the Impulsiveness Questionnaire and questionnaires detailing severity of eating disorder. Bulimic patients had higher impulsivity scores than anorexic patients. Bulimics with high impulsivity scores did not have more severe eating disorders than low scorers. When 39 bulimics and 25 anorexics were interviewed about other impulsive behaviour, 51% of bulimics and 28% of anorexics reported at least one other impulsive behaviour. Patients with so-called 'multi-impulsive' bulimia reported more severe eating disturbance, but this was not reflected on more reliable measures of symptoms. Thirty-nine bulimics entered an eight-week treatment trial and their progress was assessed at eight weeks, 16 weeks and one year. 'Non-impulsive' bulimics had a more rapid response than 'impulsives' during treatment, but there was no difference at follow-up. There was no evidence of an association between high impulsivity trait scores and poor treatment response. It is concluded that impulsivity may shape the expression of eating disorders, but that 'multi-impulsives' do not constitute a categorically distinct subgroup of bulimics. PMID- 8435690 TI - Classification and treatment of obsessional slowness. AB - Obsessional slowness is regarded as an uncommon but severely disabling variant of obsessive-compulsive disorder. This paper examines the psychopathology, classification, pathophysiology and treatment of obsessional slowness. It argues that primary obsessional slowness does not require classification as a separate syndrome because it can be found to be secondary to recognised phenomena of obsessive-compulsive disorder or anankastic personality disorder. The treatment described in the literature is not thought to be successful in the long term, and controlled trials are required to evaluate new strategies and antidepressant medication. PMID- 8435691 TI - Psychiatric referrals within the general hospital: comparison with referrals to general practitioners. AB - The increase in referrals to a new consultant psychiatrist within a teaching hospital was documented. During 1987/88 there were 279 consecutive referrals from physicians and surgeons (159 out-patients and 120 ward-consultation requests) which were compared with 184 consecutive GP referrals over the same period. Hospital referrals tended to be older, and less socially disadvantaged, but with psychiatric disorder of similar severity to GP referrals. They were more likely to have a concurrent physical diagnosis, and demonstrate somatisation. The latter was not confined to patients without physical disorder; half of the patients classified as 'psychological reaction to physical disorder' showed somatisation. ICD-10 appeared to perform better than ICD-9 or DSM-III for somatoform disorders, but a comprehensive classification system is still needed for liaison psychiatry. Personal discussion with the referring doctor was most common among the ward consultation requests; in this situation the referring doctor usually continued primary management of the patient. PMID- 8435692 TI - The problem of detecting changes in the incidence of schizophrenia. AB - Despite reports of falling first-admission rates for schizophrenia in the UK and other Western countries, it would be rash to conclude that the incidence of schizophrenia is falling. An attempt was made to tackle the many methodological problems and sources of bias influencing the relationship between admission rates and incidence in an analysis of inception rates for schizophrenia and other psychoses in Edinburgh between 1971 and 1989. However it was calculated, the inception rate for schizophrenia fell significantly, but because there was evidence that diagnostic criteria for schizophrenia had narrowed between 1971 and 1989, and because a substantial and changing proportion of recorded first admissions were not true first admissions, it was impossible to conclude that the incidence of schizophrenia had fallen. Changes in the incidence of psychiatric syndromes are difficult to establish, particularly in retrospect, and future studies must pay more attention to the many possible confounding influences. PMID- 8435694 TI - Nosology, taxonomy and the classification conundrum of the functional psychoses. AB - The theory underlying medical classification is not always given sufficient regard. Here systematic methods developed in biology are summarised and compared with parallel developments in nosology. The classification of the functional psychoses is discussed as an example of a methodological problem in medicine. We consider that cladism could have a useful application in nosology, and could lead to classifications based on the concept of interrelationships of disease. PMID- 8435693 TI - The Nottingham study of neurotic disorder. Effect of personality status on response to drug treatment, cognitive therapy and self-help over two years. AB - Repeated assessments of psychopathology, together with personality status, were made over two years on 181 psychiatric out-patients with generalised anxiety disorder (59), panic disorder (66), or dysthymic disorder (56) diagnosed using an interview schedule for DSM-III. Patients were randomly allocated to drug treatment, cognitive and behaviour therapy, or a self-help treatment programme. Although there were no overall differences in compliance rate and efficacy between the three modes of treatment, the psychological treatment methods, particularly self-help, were more effective in patients without personality disorder, and those with personality disorder responded better to drug treatment, primarily antidepressants. The findings suggest that assessment of personality status could be a valuable aid to selection of treatment in neurotic disorders and that self-help approaches are particularly valuable once personality disorder has been excluded. PMID- 8435695 TI - Home-based care and standard hospital care for patients with severe mental illness: a randomised controlled trial. AB - "OBJECTIVE--To compare the efficacy of home based care with standard hospital care in treating serious mental illness. DESIGN--Randomised controlled trial. SETTING--South Southwark, London. PATIENTS--189 patients aged 18-64 living in catchment area. 92 were randomised to home based care (daily living programme) and 97 to standard hospital care. At three months' follow up 68 home care and 60 hospital patients were evaluated. MAIN OUTCOME MEASURES--Use of hospital beds, psychiatric diagnosis, social functioning, patients' and relatives' satisfaction, and activity of daily living programme staff. RESULTS--Home care reduced hospital stay by 80% (median stay 6 days in home care group, 53 days in hospital group) and did not increase the number of admissions compared with hospital care. On clinical and social outcome there was a non-significant trend in favour of home care, but both groups showed big improvements. On the global adjustment scale home care patients improved by 26.8 points and the hospital group by 21.6 points (difference 5.2; 95% confidence interval--1.5 to 12). Other rating scales showed similar trends. Home care patients required a wide range of support in areas such as housing, finance, and work. Only three patients dropped out from the programme. CONCLUSIONS--Home based care may offer some slight advantages over hospital based care for patients with serious mental illness and their relatives. The care is intensive, but the low drop out rate suggests appreciation. Changes to traditional training for mental health workers are required." PMID- 8435696 TI - Taste responsiveness in anorexia nervosa. AB - Preferences for sugar/fat mixtures were examined in 12 anorectic females and in 14 normal-weight volunteer controls. The subjects, recruited at an eating disorders clinic in Paris, were tested after an overnight fast and 2 hours after lunch. Anorectic patients disliked the taste of foods rich in fat more than did controls. Perceptions and preferences for sweet taste did not differ between anorectic females and controls. After lunch, taste preference ratings were equally reduced in both groups, suggesting that satiety aversion to sucrose is present even in anorexia nervosa. PMID- 8435698 TI - Ganser syndrome followed by major depressive episode. AB - A case of complete Ganser syndrome resolved after one week, but was immediately followed by a major depressive episode. The two disorders had a common cause, which is best encapsulated in a psychodynamic formulation. PMID- 8435697 TI - Blood-letting in bulimia nervosa. AB - Three cases of blood-letting in association with bulimia nervosa are reported. This association has not previously been described. PMID- 8435699 TI - Wilson's disease and catatonia. AB - A 12-year-old Indian boy presented to a psychiatric unit with catatonia. He was subsequently diagnosed to have Wilson's disease. Symptoms improved on treatment with penicillamine, zinc sulphate, and benzodiazepines. PMID- 8435700 TI - Sporadic Pick's disease in a 28-year-old woman. AB - Pick's disease was diagnosed in a 28-year-old woman without a family history of dementia (or other psychiatric disorder), after an initial diagnosis of functional psychosis and management with ECT and neuroleptics. The case illustrates the need for detailed neurological and cognitive testing and consideration of neurodegenerative disorders even in young patients. PMID- 8435701 TI - Unilateral auditory hallucinations. PMID- 8435702 TI - Personality disorder and self-report questionnaire. PMID- 8435703 TI - Combination treatment of depression. PMID- 8435704 TI - Incidence and epidemiology of schizophrenia in Denmark. PMID- 8435705 TI - Origins of delusions. PMID- 8435706 TI - The 'myth' of suicide prevention. PMID- 8435707 TI - Professional and lay opinions on multiple personality disorder. PMID- 8435708 TI - Cannabis and the PSE. PMID- 8435709 TI - Gender difference of schizophrenia in seasonal admissions in Scotland. PMID- 8435710 TI - Estimating premorbid IQ in schizophrenia. PMID- 8435711 TI - Catatonia and not neuroleptic malignant syndrome. PMID- 8435712 TI - Simultaneous kidney disease and manic-depressive psychosis. PMID- 8435713 TI - Down's syndrome, longevity, and Alzheimer's disease. PMID- 8435714 TI - Eating disorders in Hong Kong. PMID- 8435715 TI - The cost effectiveness of urethral stents. PMID- 8435716 TI - Arrhythmia during extracorporeal shock wave lithotripsy. AB - A prospective study of arrhythmia during extracorporeal shock wave lithotripsy (ESWL) was performed in 50 patients, using an EDAP LT01 piezoelectric lithotriptor. The 12-lead standard ECG was recorded continuously for 10 min before and during treatment. One or more atrial and/or ventricular ectopic beats occurred during ESWL in 15 cases (30%). The occurrence of arrhythmia was similar during right-sided and left-sided treatment. One patient developed multifocal ventricular premature beats and ventricular bigeminy; another had cardiac arrest for 13.5 s. It was found that various irregularities of the heart rhythm can be caused even by treatment with a lithotriptor using piezoelectric energy to create the shock wave. No evidence was found, however, that the shock wave itself rather than vagal activation and the action of sedo-analgesia was the cause of the arrhythmia. For patients with severe underlying heart disease and a history of complex arrhythmia, we suggest that the ECG be monitored during treatment. In other cases, we have found continuous monitoring of oxygen saturation and pulse rate with a pulse oximeter to be perfectly reliable for raising the alarm when depression of respiration and vaso-vagal reactions occur. PMID- 8435717 TI - Transitional cell carcinoma of the bladder presenting during pregnancy. PMID- 8435718 TI - Enterovesical fistula caused by small bowel lymphoma. PMID- 8435719 TI - Carcinoma of the prostate presenting with a cerebral metastasis. PMID- 8435720 TI - Management of erections during transurethral surgery using ethyl chloride spray. PMID- 8435722 TI - Use of a J guidewire for the difficult catheter change. PMID- 8435721 TI - Endoscopic treatment of ureterocele in a duplex system. PMID- 8435723 TI - Correct positioning of the donor artery during renal transplantation. PMID- 8435724 TI - The Vac-Pac in open renal surgery. PMID- 8435725 TI - Emergency orchiectomy under sedoanalgesia for uraemic ureteric obstruction secondary to prostatic carcinoma. An alternative to percutaneous and stenting procedures. PMID- 8435726 TI - Re: Long-term follow-up of women treated with perurethral teflon injections for stress incontinence. PMID- 8435727 TI - Re: Transurethral Polytef injection for post-prostatectomy urinary incontinence and Long-term follow-up of women treated with periurethral Teflon injections for stress incontinence. PMID- 8435728 TI - Re: Why renography can fail in the diagnosis of upper urinary tract obstruction. PMID- 8435729 TI - Re: Why renography can fail in the diagnosis of upper urinary tract obstruction. PMID- 8435730 TI - Risk of bacteraemia during extracorporeal shock wave lithotripsy. AB - Extracorporeal shock wave lithotripsy (ESWL) is widely used to treat urinary calculi. With increasing numbers of ESWL, more patients prone to infectious complications will be treated. However, little is known about the infectious risks of ESWL. To provide a basis for the rational use of antimicrobial prophylaxis, we studied the incidence of bacteraemia during ESWL. A total of 23 patients with urinary calculi were treated. Blood cultures (4-7 per patient) were taken before, during and immediately after ESWL, adding up to a total of 154 cultures. In 22 of these patients no bacteraemia was detected. In 1 patient small numbers of 2 different micro-organisms were found in 2 blood samples only. This finding, and the circumstances of blood collection, suggested contamination rather than bacteraemia. It was concluded that the risk of bacteraemia during ESWL is very low. PMID- 8435731 TI - Ploidy and prognosis in renal carcinoma. AB - The value of tumour ploidy status as a prognostic indicator in renal carcinoma is disputed. In this retrospective study the DNA content of 90 primary and 10 secondary renal cell carcinomas was measured using flow cytometry. Data on recurrence and survival were available in all cases. Tumours were staged according to the TNM system and histological grade was based on nuclear morphology. Formalin-fixed, paraffin-embedded material was processed using standard techniques. Multiple samples were examined in 19 cases. Of the primary tumours, 52 were diploid, 24 were aneuploid and 6 were tetraploid; 8 patients had uninterpretable histograms. Ploidy of the secondary tumours was similar to that of their respective primaries. Aneuploidy correlated with higher grade but not with TNM category and, although associated with an increased risk of death, did not provide independent prognostic information. Heterogeneity of ploidy was found in 6 of the 19 cases where more than 1 sample was assessed. It was concluded that tumour DNA content in renal carcinoma is weakly linked to outcome, is subject to sample error and does not provide accurate prognostic information as a single independent variable. PMID- 8435732 TI - Periurethral Teflon for stress urinary incontinence: medium-term results. AB - Medium-term results are presented for the periurethral injection of Teflon in the treatment of stress urinary incontinence. Follow-up data were obtained on 36 women by means of case note review and the completion of a postal questionnaire. Mean follow-up was 5.1 years. Subjective results showed 12 patients to be dry or much improved while the remaining 24 patients did not obtain significant benefit from the procedure. Repeat injections in 12 women resulted in only 3 obtaining useful improvement, while a subgroup of patients who had undergone previous procedures showed a better response. No significant complications were observed. Periurethral Teflon injection is a minor surgical procedure which can produce worthwhile improvement, although an initially good result may not be sustained with longer follow-up. This method may be advocated as treatment for poor risk patients who are unsuitable for surgery, particularly when previous attempts at formal surgical correction have been unsuccessful. PMID- 8435733 TI - Ultrastructural observations on cystitis cystica in human bladder urothelium. AB - Cystitis cystica, a common urothelial pathology whose aetiology, morphology and clinical significance are poorly understood, affects the human urinary bladder and trigone in both sexes. We have studied the fine structure of urothelial cysts in 11 patients diagnosed cystoscopically as suffering from cystitis cystica. Several abnormal features were observed in the adjacent urothelium, including large intracellular vacuoles (4 patients), Brunn's nest (5), lymphocyte infiltration (10) and generally disorganised urothelial architecture (10). Squamous metaplasia was observed in one case. The wall of each cyst consisted of a 2-3 layered epithelium with either tall columnar or flattened cells lining the fluid-filled lumen. Both types of lining cell possessed short microvilli, while the columnar type also contained numerous membrane-bound, electron dense secretory granules in the apical cytoplasm. Rough endoplasmic reticulum, mitochondria and Golgi membranes were plentiful in the surface cells. Junctional complexes joined adjacent lining cells. The deeper cells contained relatively fewer organelles, while a basal lamina separated the cyst wall from the underlying connective tissue. PMID- 8435734 TI - Why do most primary bladder neoplasms first appear around the ureteric orifices? AB - The majority of primary bladder neoplasms are known to arise within the mucosa around the ureteric orifices and bladder base. This may be due to the mucosa in this area being more susceptible to carcinogens than other areas of the bladder. Deficiency in the nucleotide salvage pathway enzyme thymidine kinase (TK), and especially its TK1 isozyme, has been shown to predispose cell lines to increased mutagenesis. Total TK and TK1 activities were measured in mucosal samples taken adjacent to the ureteric orifices and dome in 32 normal bladders and both total TK and TK1 were shown to be significantly decreased in the mucosa adjacent to the ureteric orifices. This may explain why primary bladder neoplasms occur more commonly in this site. PMID- 8435735 TI - Detection of non-palpable prostate cancer. A mathematical and laboratory model. AB - Prostate cancer is currently the most commonly diagnosed cancer among males in the United States. As technology improves and the search for this enigmatic condition intensifies, we are detecting greater numbers of non-palpable tumours. These tumours are generally treated aggressively, given the uncertainty of their behaviour, but this approach may be over-zealous for small volume disease. The likelihood of detecting any cancer volume can be derived from Bayes' theorem of conditional probability. A laboratory model using coloured clay was created to contrast tumour volumes of 2.5, 5 and 20% (n = 75). Six random systematic biopsies were taken from each model in a blind fashion; 36% of the 2.5%, 44% of the 5% and all of the 20% models had at least 1 positive biopsy. Twenty-two of the 25 models representing 20% tumour had 3 or more biopsy cores positive. These data suggest that low volume disease with low biological potential will be found by random biopsy as the mathematical probability predicts. The high incidence of occult prostate cancer in the older population makes this a worrying observation. Also, and perhaps more important, there is a direct correlation between the volume of disease and the number of positive biopsies. This correlation is easily seen in both models and may allow for an estimation of tumour volume. This ability to estimate tumour volume may be a useful clinical tool that helps to guide therapy and assess prognosis. PMID- 8435736 TI - Urinary continence following radical retropubic prostatectomy. AB - Between 1983 and 1989, 484 men (46-82 years old) underwent radical retropubic prostatectomy for prostate cancer. Six months after surgery, 434 patients (90%) achieved complete urinary control; stress incontinence was present in 50 patients (10%) and no patient was totally incontinent. Of the 398 patients who were followed up for more than 1 year, 377 (95%) achieved complete urinary control and 21 (5%) experienced stress incontinence. Prior open prostatectomy or transurethral resection of the prostate had no influence on the return of urinary control. Pathological stage and preservation or not of the neurovascular bundles also had no significant influence on the long-term state of continence. Age was the only factor that adversely affected the return of urinary continence. The average interval between surgery and return of continence was shorter in patients less than 70 years old. When the impact of age was examined 1 year or more after surgery, no significant difference was noted between the age groups. Several technical considerations that contribute to these results are discussed, especially the use of a gradual approach to the apex of the prostate to facilitate exposure and haemostasis and to preserve as much of the striated urethral sphincter as possible. PMID- 8435737 TI - Decontamination of urological equipment: interim report of a working group of the Standing Committee on Urological Instruments of the British Association of Urological Surgeons. PMID- 8435738 TI - Pelvic floor exercise versus surgery in the treatment of impotence. AB - A group of 150 consecutive male patients with erectile dysfunction and proven venous leakage were randomised either to surgery or to a pelvic floor training programme. The operative procedure consisted of dissection and removal of the deep dorsal vein of the penis and its tributaries or large veins that drain into the internal or external pudendal system. The training programme was given 5 times, in weekly sessions, and the patients were supervised by trained physiotherapists. Surgery was not superior to the pelvic floor training programme either subjectively or objectively. Moreover, a significant improvement was found following the training programme; 42% were satisfied with the outcome and refused surgery. Pelvic floor exercise is a realistic alternative to surgery in patients with mild degrees of venous leakage. PMID- 8435739 TI - Sclerosing lipogranuloma of the male genitalia: analysis of the lipid constituents and histological study. AB - An analysis of lipids and histological examination were performed on tissues resected from 2 patients with sclerosing lipogranuloma of the scrotum. The clinical course and histological characteristics were consistent with those reported previously for typical primary sclerosing lipogranuloma of the male genitalia. There was no history of the injection or topical application of oils or fats. Both of our patients had eosinophilia and the lesions showed eosinophilic infiltration. Complete natural regression occurred several months after partial resection of the lesion in both cases, and no recurrence has been noted during follow-up. This lipid analysis and histological study revealed that no exogenous fatty elements were present and suggested that degeneration of endogenous fat due to some allergic mechanism might be involved in the development of sclerosing lipogranuloma. The eosinophilia associated with this disease and its spontaneous regression after partial resection also support this assumption. PMID- 8435740 TI - Follow-up evaluation of anomalies of the vesicoureteric junction. AB - Anomalies of the vesicoureteric junction are important, particularly obstruction and reflux, as they may predispose to urinary tract infection. Over a 5-year period, 52 babies were referred with dilatation of the urinary tract detected antenatally or/and postnatally by ultrasound. Sixteen had an anomaly of the vesicoureteric junction: 9 had vesicoureteric reflux, 3 had ureteroceles, 1 had urethral stenosis with secondary reflux and 3 had stenosis of the vesicoureteric junction. Ten patients underwent 14 surgical procedures. The mean time to reconstructive surgery was 9.3 months. Ultrasonography showed regression of the dilatation in all patients who underwent surgery. Seven patients with minor dilatation are still under observation. In only 1 case was there loss of renal parenchyma. With conservative medical treatment the patients are 1 year old before reconstructive surgery is undertaken; with reflux, however, progression may indicate earlier surgery. PMID- 8435741 TI - Abstracts of the proceedings of the Urological Society of Australasia, 45th annual scientific meeting. Adelaide, Australia, 1992. PMID- 8435742 TI - Migrating foreign body within a prostatic adenoma. PMID- 8435743 TI - Perinephric abscess as a presentation of pancreatitis. PMID- 8435744 TI - Retroperitoneal haemangiopericytoma presenting with diurnal urinary frequency. PMID- 8435745 TI - A study on the effect of lesions of area 7 of the parietal cortex on the short term visual spatial memory of rhesus monkeys (Macaca mulatta). AB - This research is focused on the contribution of area 7 to the short-term visual spatial memory. Three rhesus monkeys (Macaca mulatta) were trained in the direct delayed response task in which 5 delay intervals were used in each session. When each monkey reached the criterion of 90% correct responses in 5 successive sessions, two monkeys underwent a surgery while the other one received a sham operation as a control. In the first stage of the surgery, bilateral areas 7a, 7b and 7ip of the parietal cortex of two monkeys were precisely lesioned. After 7 days of recuperation, the monkeys were required to do the same task. The average percentage of correct responses in the lesioned animals decreased from 94.7% to 89.3% and 93.3% to 82.0% respectively (no significance, P > 0.05, n = 2). In addition, the monkeys' complex movements were mildly impaired. The lesioned monkeys were found to have difficulty picking up food from the wells. In the second stage, bilateral area 7m was lesioned. In the 5 postoperative sessions, the average percentage of correct responses in one monkey, with a relatively precise 7m lesion, decreased from 94.7% to 92.2% (no significance, P > 0.05), while the other monkey, with widely spread necrosis of lateral parietal cortex, showed an obvious decline in performance, but still over the chance level. After 240 trials this monkey reattained the normal criterion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8435746 TI - Genetic differences in the time course for the development and persistence of the anticonvulsant effects of carbamazepine against cocaine seizures. AB - Initial studies of the effect of chronic carbamazepine (CBZ) against cocaine induced seizures indicated that there were genetic differences in both the time course for the development of the anticonvulsant effects of CBZ against cocaine induced seizures and the persistence of these effects. The present studies were initiated to investigate the time course for the development and persistence of the anticonvulsant effects of chronic CBZ against cocaine seizures in BALB/cByJ, C57Bl/6J and SJL/J mice. The anticonvulsant actions of CBZ were dependent on the duration of CBZ administration, requiring 4-7 days to achieve maximal efficacy. However, once the anticonvulsant effects of CBZ were manifest, the effect persisted for up to 5 days after stopping CBZ treatment depending on the genotype. The levels of CBZ and its active epoxide metabolite were determined in plasma and brain at various time points during and after chronic CBZ treatment. The levels of CBZ and CBZ-10,11-epoxide were substantially reduced over the course of treatment in all three strains, such that the levels of the two compounds in plasma and brain could not account for the decreased susceptibility to cocaine seizures observed following chronic CBZ. These results suggest that the effects of CBZ on cocaine seizures are mediated by relatively long-term changes in one or more biological systems associated with cocaine's convulsant effects. PMID- 8435747 TI - Subsensitivity of lead-exposed rats to the accuracy-impairing and rate-altering effects of MK-801 on a multiple schedule of repeated learning and performance. AB - Exposure to lead (Pb) has been reported to inhibit MK-801 binding and to alter other NMDA receptor complex-associated functions. These reported changes are provocative since both NMDA receptor antagonism and Pb exposure are know to impair learning processes. Whether the Pb-induced changes in NMDA function relate to the learning impairments associated with Pb exposure, however, has not been explored. The contention of this study was that if changes in NMDA function produced by Pb serve as the basis of Pb-associated learning impairments, then such changes should be of sufficient biological magnitude and clinical relevance to induce alterations in sensitivity at the level of the whole animal, i.e., changes in behavioral sensitivity to glutamatergic compounds. Thus, in this study, dose-effect curves of control and Pb-treated rats working on a multiple schedule of repeated learning (repeated acquisition, RA) and performance (P) were compared following acute administration of MK-801, the non-competitive NMDA antagonist. Based on the nature of the reported effects of Pb on NMDA systems, it was expected that the curves of Pb-exposed rats would be right-shifted relative to controls, if differential behavioral sensitivity was evident. Rats were chronically exposed to 0, 50 or 250 ppm Pb acetate in drinking water from weaning and trained on the multiple RA and P schedule beginning at 55 days old. The RA component required the rat to learn a new 3-member sequence of responses during each experimental session (center right left, RLC, CLR, RCL, or LRC), while the correct sequence of responses for the P component was constant across sessions (LCR), requiring performance of an already learned response. Acute administration of MK-801 (0.05-0.3 mg/k, i.p.) resulted in decrements in accuracy in both the RA and P components of the schedule, indicative of non-specific effects on behavior rather than selective effects on learning. The declines in accuracy during the RA component of the schedule were primarily the result of increased perseverative responding, i.e., repetitive responding on a single lever. Both the decline in RA accuracy and the increases in perseverative responding produced by MK-801 were attenuated by Pb exposure. Moreover, dose-effect curves relating MK-801 dose to changes in rates of responding were significantly shifted to the right in Pb exposed rats relative to controls. Taken together, these data demonstrate a subsensitivity of Pb-exposed rats to both the accuracy-impairing and response rate-altering properties of MK-801.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8435748 TI - The dopaminergic innervation of the pigeon caudolateral forebrain: immunocytochemical evidence for a 'prefrontal cortex' in birds? AB - The dopaminergic (DA) innervation of the caudal telencephalon of the pigeon was investigated with an antiserum against glutaraldehyde-conjugated dopamine. It was found that the DA-like fibers were distributed within the Paleostriatum augmentatum and the dorsal Archistriatum in a dense meshwork of fibers, while most of the remaining part of the caudal forebrain was innervated by dopaminergic axons which were coiled up like baskets around unlabelled neurons. Within the basket-type innervated structures, the Neostriatum caudolaterale (Ncl) could be distinguished by the high density of its dopaminergic fibers. Retrograde tracer injections into Ncl revealed afferents from the Area ventralis tegmentalis (AVT) and the n. tegmenti pedunculo-pontinus pars compacta (TPc). Since large numbers of DA-like perikarya could be detected in AVT and TPc, it is supposed that these two structures constitute the main source of the dopaminergic innervation of the Ncl. Previous studies had suggested that the Ncl represents an avian equivalent to the mammalian prefrontal cortex. The present results reveal an organization similar to that of the mesocortico-prefrontal system and would thus strengthen this hypothesis. PMID- 8435749 TI - Ischemia-induced changes in alpha-tubulin and beta-actin mRNA in the gerbil brain and effects of bifemelane hydrochloride. AB - Using in situ hybridization histochemistry, we examined changes in the cytoskeletal protein alpha-tubulin and beta-actin mRNAs in the gerbil brain 14 days after transient ischemia. In an attempt to identify the changes induced in the synthesis of cytoskeletal protein by ischemia, we also evaluated the effects of post-ischemia administration of bifemelane on these cytoskeletal proteins. alpha-Tubulin and beta-actin mRNAs were decreased in the CA1 region 14 days after transient ischemia. These decreases coincided with the loss of CA1 pyramidal cells, suggesting that they may have been related to delayed neuronal death. The beta-actin mRNA level in ischemic controls was significantly increased in the dentate gyrus, habenular nucleus, and medial and lateral thalamic nuclei, where some afferent nerves project into the hippocampal pyramidal cells. The increased beta-actin mRNA suggests that there may be a compensatory enhancement of actin synthesis in the afferent neurons that restores loosened synaptic connections with the ischemic cells in the CA1-4 fields. Administration of bifemelane just after recirculation prevented most of the ischemia-induced mRNA reductions in the CA1 field. Bifemelane's effect may be related to inhibition of Ca2+ influx and its radical scavenging activity. When bifemelane was administered to the ischemic group, alpha-tubulin mRNA levels significantly increased in the dentate gyrus and amygdaloid nucleus, and beta-actin mRNAs showed a tendency to increase in the CA3 and CA4 fields, dentate gyrus, and medial and lateral thalamic nuclei. These findings suggest that bifemelane may enhance synthesis of cytoskeletal protein, especially in the ischemic brain, inducing axon outgrowth or synapse formation. PMID- 8435750 TI - Time- and dose-dependent effects of the serotonergic agent quipazine on regional cerebral metabolism in rats. AB - The time course and the relation to dose of regional cerebral metabolic rates for glucose (rCMRglc) were measured in awake male adult Fischer-344 rats after administration of quipazine, a serotonin 5-HT2-3 receptor agonist. rCMRglc was determined, using the quantitative autoradiographic [14C]deoxyglucose technique, in 92 brain regions at 30, 60, 90 and 120 min after quipazine 20 mg/kg i.p. and at 60 min after quipazine 5 mg/kg i.p. Peak metabolic effects were observed 60 min after quipazine 20 mg/kg i.p. when rCMRglc was significantly elevated in 27 (29%) brain regions (mean rise 17%). Quipazine increased rCMRglc in brain regions with high densities of 5-HT3 receptors (area postrema, olfactory tubercle, amygdala), in dopaminergic nuclei (substantia nigra pars compacta and pars reticulata) and terminal fields of their projections (zona incerta, subthalamic nucleus, preoptic magnocellular area, nucleus of facial nerve). The topographic distribution and direction of rCMRglc changes induced by quipazine are different from those produced by the 5-HT2 agonist 1-(2,5-dimethoxy-4-iodophenyl)-2 aminopropane and, consistent with the pharmacological and binding properties of quipazine, suggest a preferential activation of 5-HT3 receptors. PMID- 8435752 TI - Intracellular concentration of parvalbumin in nerve cells. AB - Parvalbumin is supposed to function as an intracellular Ca2+ buffer in the brain, but its concentration in nerve cells is unknown. We combined radioimmunoassay of parvalbumin in rat brain extracts, together with image analysis of area fractions immunostained with the parvalbumin antibody on sections, to deduce the intracellular concentration of parvalbumin. We found that the average amount of parvalbumin varied between 6 microM in the caudatoputamen and 45 microM in the cerebellum. Although these values are only rough averages and do not demonstrate a Ca2+ buffering role for parvalbumin in neurons, the concentration of the protein is at least in the appropriate range for such a function. PMID- 8435751 TI - Calcium homeostasis in rat septal neurons in tissue culture. AB - Septal neurons from embryonic rats were grown in tissue culture. Microfluorimetric and electrophysiological techniques were used to study Ca2+ homeostasis in these neurons. The estimated basal intracellular free ionized calcium concentration ([Ca2+]i) in the neurons was low (50-100 nM). Depolarization of the neurons with 50 mM K+ resulted in rapid elevation of [Ca2+]i to 500-1,000 nM showing recovery to baseline [Ca2+]i over several minutes. The increases in [Ca2+]i caused by K+ depolarization were completely abolished by the removal of extracellular Ca2+, and were reduced by approximately 80% by the 'L-type' Ca2+ channel blocker, nimodipine (1 microM). [Ca2+]i was also increased by the excitatory amino acid L-glutamate, quisqualate, AMPA and kainate. Responses to AMPA and kainate were blocked by CNQX and DNQX. In the absence of extracellular Mg2+, large fluctuations in [Ca2+]i were observed that were blocked by removal of extracellular Ca2+, by tetrodotoxin (TTX), or by antagonists of N-methyl D-aspartate (NMDA) such as 2-amino 5-phosphonovalerate (APV). In zero Mg2+ and TTX, NMDA caused dose-dependent increases in [Ca2+]i that were blocked by APV. Caffeine (10 mM) caused transient increases in [Ca2+]i in the absence of extracellular Ca2+, which were prevented by thapsigargin, suggesting the existence of caffeine-sensitive ATP-dependent intracellular Ca2+ stores. Thapsigargin (2 microM) had little effect on [Ca2+]i, or on the recovery from K+ depolarization. Removal of extracellular Na+ had little effect on basal [Ca2+]i or on responses to high K+, suggesting that Na+/Ca2+ exchange mechanisms do not play a significant role in the short-term control of [Ca2+]i in septal neurons. The mitochondrial uncoupler, CCCP, caused a slowly developing increase in basal [Ca2+]i; however, [Ca2+]i recovered as normal from high K+ stimulation in the presence of CCCP, which suggests that the mitochondria are not involved in the rapid buffering of moderate increases in [Ca2+]i. In simultaneous electrophysiological and microfluorimetric recordings, the increase in [Ca2+]i associated with action potential activity was measured. The amplitude of the [Ca2+]i increase induced by a train of action potentials increased with the duration of the train, and with the frequency of firing, over a range of frequencies between 5 and 200 Hz. Recovery of [Ca2+]i from the modest Ca2+ loads imposed on the neuron by action potential trains follows a simple exponential decay (tau = 3-5 s). PMID- 8435753 TI - Voltammetry of extracellular dopamine in rat striatum during ICSS-like electrical stimulation of the medial forebrain bundle. AB - Fast-scan cyclic voltammetry in the striatum of anesthetized rats has been used to monitor extracellular dopamine during forced electrical stimulation of the media forebrain bundle using parameters that mimic intracranial self-stimulation. The temporal resolution provided by microelectrodes positioned very near sites of dopamine release allows resolution of the response to individual 500-ms stimulation trains separated by 500-ms intervals. Uptake inhibition by Nomifensine alters the resolution obtained at short times after initiation of stimulation. PMID- 8435754 TI - Ascending and descending convergent inputs to neurons in the nucleus parabrachialis of the rat: an intracellular study. AB - Responses of the nucleus parabrachialis neurons (PBN) to electrical stimulation of the lateral hypothalamus (HL), central nucleus of the amygdala (Ac), dorsolateral funicullus in the spinal cord (SC), mediocaudal nucleus tractus solitarius (NTS), and substantia nigra (SN) were investigated in anesthetized rats by intracellular recording technique. Convergent excitatory postsynaptic potentials (EPSPs) were evoked on 8 of 36 neurons tested by both HL and NTS stimulation. The EPSPs evoked by HL stimulation were characterized as monosynaptic in 4 neurons. The EPSPs evoked by SC stimulation were characterized as monosynaptic in 2 of 36 neurons, moreover, these neurons were also antidromically activated by HL stimulation. Stimulation of Ac evoked EPSPs on 10 of 36 cells tested; 8 demonstrated to be monosynaptic. In addition, IPSP evoked by SN stimulation and EPSP evoked by NTS stimulation converged on three neurons. The results indicate that ascending and descending inputs converge on lateral PBN neurons. PMID- 8435755 TI - Effects of long-stimulus intervals and scopolamine administration on hippocampal kindling. AB - Using the low-frequency kindling procedure, we studied the effects of periodic 2 week stimulus-free intervals and chronic scopolamine administration on hippocampal kindling seizure development. In Experiment 1, rats were divided into two groups, interval group and no-interval group. In the interval group a 2-week stimulus interval was set after every five consecutive daily stimulations until the 21st stimulation. The number of stimulating pulses required for the triggering of epileptic afterdischarge, pulse-number threshold (PNT), was used as an indicator of the seizure threshold. PNT, afterdischarge duration (ADD) and behavioral seizure stage (BSS) of each induced seizure in the initial stage of kindling, kindling rate, seizure parameters at the completion of kindling were recorded and compared to the values of the no-interval, control group. Our result showed that PNT at the 6th stimulation, the first stimulation after the first 2 week stimulus interval increased significantly compared to control. Other seizure parameters did not differ significantly between the two groups. In Experiment 2 scopolamine hydrobromide, 0.5 and 1.0 mg/kg i.p., was administered 1 h before each electrical stimulation until each rat showed the stage-3 seizure. PNT, ADD and BSS in the initial stage of kindling, kindling rate for the stage-3 and -5 seizures, seizure parameters at the first stage-3 and -5 were recorded and compared to the values of saline-treated, control group. Although scopolamine 1.0 mg/kg increased PNT at the 5th stimulation compared to control, no other significant changes of the seizure parameters were found by scopolamine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8435756 TI - Co-localization of two calcium binding proteins in GABA cells of rat piriform cortex. AB - In the rat piriform cortex, double-fluorescence immunocytochemistry was used to study the coexistence of two calcium binding proteins, parvalbumin and calbindinD28k, and GABA. Layer I cells were immunoreactive only for GABA. In layer II a small number of cells were immunoreactive for all three substances. A few other cells contained only parvalbumin and GABA immunoreactivity. In layer III a subpopulation of calbindinD28k immunoreactive cells (about 60%) were also immunoreactive for both parvalbumin and GABA. The remainder showed only calbindinD28k and GABA immunoreactivity. Many immunoreactive terminals, which surrounded non-immunoreactive cell somata to form basket endings in layers II and III, were immunoreactive for all three substances. Their major source may be the non-pyramidal neurons in layer III, which contained the three chemical substances. PMID- 8435757 TI - Maturation-related changes in tolerance development to hexobarbital after short term treatment with diazepam in the rat. AB - Male rats at six different ages received diazepam on a 4-day treatment schedule. Cross-tolerance to hexobarbital was tested several times during withdrawal period with an anaesthesia threshold technique. Pattern of cross-tolerance was different at different ages. Thus, age and maturation of the rat is a variable which must be considered in studies of tolerance to diazepam. PMID- 8435758 TI - Peripheral bombesin induces c-fos protein in the rat brain. AB - Bombesin injected intraperitoneally induces c-fos protein-like immunoreactivity in the medial nucleus tractus solitarius and the parvocellular part of the paraventricular nucleus of the hypothalamus in the rat brain. C-fos expression induced by bombesin is less densely represented compared with CCK. Capsaicin pretreatment did not influence c-fos-immunoreactivity induced by bombesin and significantly reduced that induced by CCK. PMID- 8435759 TI - Reconstruction of strings past. AB - A major use of string-alignment algorithms is to compare macromolecules that are thought to have evolved from a common ancestor to estimate the duration of, or the amount of mutation in, their separate evolution and to infer as much as possible about their most recent common ancestor. Minimum message length encoding, a method of inductive inference, is applied to the string-alignment problem. It leads to an alignment method that averages over all alignments in a weighted fashion. Experiments indicates that this method can recover the actual parameters of evolution with high accuracy and over a wide range of values, whereas the use of a single optimal alignment gives biased results. PMID- 8435760 TI - Short algorithm to compensate for sampling-volume errors in diffusion-cell studies. AB - This communication describes a short algorithm enabling arbitrarily large but equal samples to be taken from the two chambers of a diaphragm diffusion cell without introducing any systematic error. It creates a transformed time-scale, dependent on sampling volume, which linearizes the output, fits this to a straight line by simple linear regression, and computes the diffusion coefficient from the slope. The advantages of sampling equal fractions from both chambers are discussed in terms of the greater precision this allows. The procedure may have uses in other fields. PMID- 8435761 TI - SIGNAL SCAN 3.0: new database and program features. AB - SIGNAL SCAN is a program that utilizes a transcription factor database to find potential transcription factor binding sites in DNA sequences. The program is now in its third version. The SIGNAL SCAN transcription factor database format has changed and the program output format has been improved. New features allow the user to update the SIGNAL SCAN database automatically, to retrieve original journal citations and to develop user signal databases. The program now uses an indexing algorithm, improving scanning speed by a factor of 3. SIGNAL SCAN is now network compatible and is available for IBM-compatible PC, Unix and VMS platforms. PMID- 8435762 TI - Fast Needleman-Wunsch scanning of sequence databanks on a massively parallel computer. PMID- 8435763 TI - A novel method of protein sequence classification based on oligopeptide frequency analysis and its application to search for functional sites and to domain localization. AB - A new method for distinguishing among protein families based on the analysis of oligopeptide composition of amino acid sequences is presented. It is assumed that any protein family can be characterized by a set of essential oligopeptides (oligopeptide vocabulary). A simple approach to find such a vocabulary is suggested. It is shown that comparison of the vocabularies can distinguish among different families and the latter from random sequences. This comparison can be successfully made with a small set of frequencies of 25 dipeptides (or tripeptides). No preliminary alignment is necessary. It is established that characteristic peptides are located in the regions of functional value, as shown for GTP-binding domains of the translation elongation factors. It is demonstrated that this method is reasonably efficient for localizing functional domains in the amino acid sequences. The average error of prediction does not exceed three or four amino acid residues as shown for several functional domains. PMID- 8435764 TI - Profile sequence analysis and database searches on a transputer machine connected to a Macintosh computer. AB - An implementation of Profilesearch (a technique to search for relationships between a protein sequence and multiply aligned sequences) for a parallel computer is described. The number-crunching machine, consisting of 21 T800 transputers, is connected to a Macintosh IIcx host computer. The program utilizes a standard Macintosh application as its user-interface, resulting in a transparent and user-friendly environment for addressing the parallel computer. The program is independent of the number of available processors and exceeds the speed of a VAXstation 3200 with only one transputer in operation, thus allowing cheap and fast database searches with a PC front-end. For a larger number of processors, the speed increase is approximately linear with no obvious symptoms of saturation with the available maximum of 21 transputers. The program and environment are useful to search quickly and easily for similarities between a single sequence or sequence set and individual sequences contained in a large database. The alignment is determined by typical dynamic programming techniques. PMID- 8435765 TI - Microcomputer BASIC programs for rapid determination of lethal dosages of biocides using logit transformations. AB - The probit analysis model is generally used for the determination of lethal dosages in bioassay applications. However, the logit models, which use the logistic curve instead of the integrated normal curve, could also be effectively used for the determination of lethal dosages and regression coefficients. In this paper, two types of logit models, namely minimum logit chi square and maximum likelihood, have been described in detail for the estimation of the parameters. The results of these two models are also compared with those of the probit model. PMID- 8435766 TI - MANSEK and SUNHCA. Two interactive programs for the hydrophobic cluster analysis of protein sequences. AB - Hydrophobic cluster analysis (HCA) is an efficient method for analysing and comparing the amino acid sequences of proteins. It relies on two-dimensional representations of the sequences presently generated by simple plot programs working on microcomputers. Two interactive programs, MANSEK and SUNHCA, are described here that operate from Vax and Sun workstations respectively. These programs allow the display of several protein sequences in the form of two dimensional helical plots suitable for HCA. Several tedious, repetitive and time consuming steps of HCA have been suppressed by implementing several features such as interactive on-screen manipulations (zoom, translations) of the plots and HCA score calculations on segments chosen by the user. Plots on paper can be obtained through hard copies or plotting subroutines. PMID- 8435767 TI - Sample size calculation, power analysis and randomization: research project design in Windows. AB - Single estimates of sample size for a study may be easily obtained by use of a hand calculator or from published tables. In contrast, performing multiple calculations is a tedious and time-consuming task, which is greatly simplified by a computer program. The computer program presented here assists the investigator in calculating sample size estimates, determining statistical power and creating randomization tables for a study. The program is designed primarily for clinical trials and thus includes some features not found in other software packages performing similar tasks. Sample size calculation and power analysis are performed for dichotomous, continuous (parametric and non-parametric tests) and time-to-failure (exponential distribution and log-rank test) response variables, and for correlation coefficients. Sample size estimates and significance levels may be adjusted for multiple participating centers, non-compliance, interim analyses and.multiple testing. The randomization subroutine generates tables for studies with up to nine treatment arms and with any valid block size. As a Windows application, the program runs in a multitasking environment, allowing switching between programs and easy pasting of results into word-processing documents and other applications. It is very simple to use, with a completely menudriven interface and sufficient built-in help to obviate the use of a manual. PMID- 8435768 TI - SRS--an indexing and retrieval tool for flat file data libraries. AB - SRS (Sequence Retrieval System) is an information indexing and retrieval system designed for libraries with a flat file format such as the EMBL nucleotide sequence databank, the SwissProt protein sequence databank or the Prosite library of protein subsequence consensus patterns. SRS supports the data structure of these libraries by providing special indices for implementing lists of subentities (e.g. feature tables) or hierarchically structured data-fields (e.g. taxonomic classification). A language (ODD) has been designed for the convenient specification of library format and organization, representation of individual data-fields within the system (design of indices) and structuring other data needed during retrieval. This ensures flexibility required for coping with different library formats, which are subject to continuous change. Queries and inspection of retrieved entries can be performed from a user interface with pull down menus and windows. SRS supports various input and output formats but is particularly well adapted to the GCG programs. PMID- 8435769 TI - Transforming a set of biological flat file libraries to a fast access network. AB - SRS (Sequence Retrieval System), an indexing system for flat file libraries, provides fast access to individual library entries via retrieval by keywords from various data fields. SRS is now also able to build indices using cross-references that most libraries provide. Fifteen libraries of DNA and protein sequences and structures have been selected. These libraries interact with at least one other by means of cross-references. Indexing these cross-references allows a complete network of libraries to be built. In the network an entry from one library can be linked in principle to every other library. If two libraries are not directly cross-referenced, the linkage can be made with a succession of single links between neighbouring, cross-referenced libraries. A new operator has been added to the query language of SRS for convenient specification of links amongst complete libraries or entry sets generated by previous queries on particular libraries. All the information in the network can now be used to retrieve an entry in a specific library, e.g. the full information given in amino acid sequence entries from SwissProt can now be used to retrieve related tertiary structure entries from PDB. Furthermore, a search in a single library can be extended to a search in the complete library network, e.g. all entries in all databases pertaining to elastase can be found. PMID- 8435770 TI - Rapid motif compliance scoring with match weight sets. AB - Most current implementations of motif matching in biological sequences have sacrificed the generality of weight matrix scoring for shorter runtimes. The program MOTIF incorporates a weight matrix and a rapid, backtracking tree-search algorithm to score motif compliance with greatly enhanced performance while placing no constraints on the motif. In addition, any positions within a motif can be marked as 'inviolate', thereby requiring an exact match. MOTIF allows a choice of regular expression formats and can use both motif and sequence libraries as either targets or queries. Nucleic acid sequences can optionally be translated by MOTIF in any frame(s) and used against peptide motifs. PMID- 8435771 TI - EMBL-search: a CD-ROM based database query system. AB - This paper describes a system of generally applicable index files provided on the EMBL sequence databases CD-ROM to facilitate the development of front-end software to the sequence databases available on this CD-ROM. The index files are used by a new versatile and user-friendly database retrieval program for the Apple Macintosh, EMBL-Search, which allows the easy construction of complex database queries. EMBL-Search utilizes cross-reference information contained in the databases to support navigation between different information resources. The ability to run EMBL-Search on a local computer network accessing a shared database CD-ROM makes its use particularly cost effective. PMID- 8435772 TI - Refined algorithm and computer program for calculating all non-negative fluxes admissible in steady states of biochemical reaction systems with or without some flux rates fixed. AB - A refined algorithm together with a computer procedure for determining the complete set of non-negative, steady-state fluxes in biochemical reaction systems of any complexity, with or without some flux rates fixed, is given. It is shown that this set is a convex polyhedron, which may or may not be bounde. The algorithm is illustrated by several examples; one of them concerns intermediary metabolism. A computer code in standard C is presented. PMID- 8435773 TI - Interactive and graphic coupling between multiple alignments, secondary structure predictions and motif/pattern scanning into proteins. AB - A computer module that includes multiple alignments, secondary structure prediction, and site and pattern search has been developed and integrated into our ANTHEPROT software for protein sequence analysis. All the programs can be invoked from within any routine, thus yielding multiple pathways to obtain final results. All the results are graphically displayed. The main feature of this module is that all methods are connected in an interactive graphic manner. This module has been designed to display easily the potential sites with conserved predicted structures. PMID- 8435774 TI - Searching for amino acid sequence motifs among enzymes: the Enzyme-Reaction Database. AB - Recently we have constructed a database--the Enzyme-Reaction Database--which links a chemical structure to amino acid sequences of enzymes that recognize the chemical structure as their ligand. The total number of enzymes registered in the database is 1103 with 6668 NBRF-PIR entry codes and 1756 chemical compounds. The chemical structures and chemical names for 842 compounds are registered in the Chemical-Structure Database on the MACCS system. For each enzyme, the sequences were divided into clusters, and multiply aligned in each cluster to extract a conserved sequence. A total of 158,781 five-residue-long fragments were constructed from 433 conserved sequences and compared among different clusters of different enzymes. One of these motifs shared by different enzymes was S-G-G-L-D. The motif was conserved in both argininosuccinate synthase (EC 6.3.4.5) and asparagine synthase (glutamine-hydrolysing) (EC 6.3.5.4). This result showed that the database was useful for the analysis of the relationship between chemical structures and amino acid sequence motifs. PMID- 8435776 TI - Clinical recognition of sexually abused children. PMID- 8435775 TI - An algorithm for the identification of similar oligopeptides between amino acid sequences. AB - Molecular mimicry is the origin of common structural patterns in sequences of viral and host proteins, and it appears to be related to the development of autoimmune diseases. The identification of structural molecular similarities among viral and host proteins is thus very relevant in the development of engineered antiviral vaccines to avoid potentially dangerous effects. In this respect identifying pairs of similar oligopeptides between given proteins, independently of the overall degree of similarity of their amino acid sequences, is of interest. To this aim we have designed and implemented an algorithm capable of finding and classifying (with respect to their statistical significance) all possible pairs of similar oligopeptides between two proteins irrespective of length, number, location and ordering of the pairs along the sequences. The algorithm is very efficient and much more suited for this kind of local search than standard alignment programs. The latter, dealing with the sequences as a whole, are, in these cases, of very limited applicability. We have used the algorithm to compare a glycoprotein of the human immunodeficiency virus (HIV) type 1 and with the beta-chains of human leukocyte antigen (HLA). Besides a previously identified peptide, we have found a new peptide located in the fusion site of HIV that shares high similarity with the transmembrane domains of HLA. PMID- 8435777 TI - Sexual abuse evaluations: conceptual and empirical obstacles. AB - Evaluating children for possible sexual abuse is widely regarded as a difficult clinical endeavor. Practitioners are concerned with both the basis for professional opinions and the accuracy of their ultimate judgments. Current approaches are critically analyzed for conceptual integrity and empirical support. The authors conclude that improvements in practice will be more productive than efforts to devise a procedure for classification of cases. Implications of this approach and recommendations for further research are discussed. PMID- 8435778 TI - Clinician responses to sexual abuse allegations. AB - We conducted a survey using an experimental design to identify how and to what extent specific personal and case factors affect clinicians' judgments about sexual abuse allegations. We drew a stratified random sample of 1,635 United States clinicians from national directories of clinical social work, pediatrics, psychiatry and psychology. Six hundred and fifty-six completed questionnaires were obtained, yielding a 42% response rate. We asked each subject to read and rate, on a 6 point scale, 16 vignettes alleging sexual abuse. The scale ranged from 1 (very confident it did not occur), to 6 (very confident it did occur). On average, respondents were "slightly confident sexual abuse had occurred" (M = 4.03; SD = 0.6). This finding was significantly different from a mean of 3.50, which is the expected null result. Seven case factors affected credibility ratings at the .01 level; perpetrators' race (Caucasians viewed as perpetrators more than minorities); perpetrators' relationship to victim (family members more often seen as perpetrators); victims' race (minorities more credible as victims); victims' affect (those showing negative affect more believable); age (younger victims more often seen as victimized); behavioral changes in the victim; and perpetrator's history of substance abuse. Six clinician factors were significant at the .05 level: age (younger clinicians were more credulous), gender (females more credulous), discipline (clinical social workers more credulous), theoretical orientation (family systems oriented more credulous) and personal history of sexual or physical abuse (abuse history more credulous). PMID- 8435779 TI - Psychological testing in evaluation of child sexual abuse. AB - In order to assess the utility of psychological testing in evaluating allegations of child sexual abuse, the empirical literature is reviewed in an attempt to answer two questions. First, are there systematic and significant differences on psychological tests between sexually abused and nonabused children? Second, are these differences on psychological testing a direct result of sexual abuse, or are they a result of other coexisting factors that might cause psychological distress? Cognitive measures, personality inventories, symptomatology checklists, and projective tests with sexually abused children are reviewed. While a variety of standardized instruments have been administered to sexually abused children, relatively few have been utilized in empirical studies. Findings have been mixed, with stronger differences between sexually abused and nonabused children generally found on measures completed by parents than on measures administered directly to children. Sexually abused children often fall between nonabused and psychiatric groups. Use of measures specific to sexual abuse is advocated. While psychological tests may currently have limited use in validating suspected sexual abuse, they may be extremely useful in the clinical treatment of the child. PMID- 8435780 TI - Children's drawings. AB - Children's drawings have been used in clinical interviews to provide direction for recollection and memory of events. Drawings encourage the retrieval of experience in the motoric, visual, and auditory recall. The drawing itself gives an expression of motor sensory discharge; the objects in the drawing help with the perceptual cues that are remembered; the cognitive dimensions are represented in the organization, interpersonal patterns, and verbal discussion of the picture. The premise of this paper is that children's drawings are useful as an associative tool for assessing and accessing traumatic memories. PMID- 8435781 TI - Assessing suspected child molesters. AB - Clinical evaluations can play a useful role in making a variety of dispositional decisions concerning child molesters provided they are done carefully, using relevant techniques, and their limitations are clearly understood. Assessment instruments and techniques that can differentiate child molesters from other persons, that are related to treatment planning, and that predict the commission of future sexual offending are the most useful. Sex offense history and phallometric assessments are useful in planning treatment and supervision programs and in assessing risk. The Psychopathy Checklist is also a strong predictor of sexual recidivism but its usefulness in treatment planning is equivocal. Measures of attitudes and beliefs that support child molestation are suitable for designing treatment programs but their prognostic significance remains to be established. More general measures of personality and psychopathology have not been established as predictors of recidivism but can be used to address collateral clinical issues. PMID- 8435782 TI - Expert testimony regarding child sexual abuse. AB - Expert testimony plays an important role in child sexual abuse litigation in criminal, juvenile, and family courts. This article discusses legal issues relating to expert testimony, including: (a) when expert testimony is permitted, (b) qualifications of expert witnesses on child sexual abuse, (c) permissible bases supporting expert testimony, (d) expert testimony on ultimate factual and legal issues, (e) the reasonable certainty standard of expert testimony, (f) the inappropriateness of equating clinical decision making with the legal degrees of proof, and (g) application of the doctrine of res judicata in litigation regarding child sexual abuse in family court. The article also provides a summary of contemporary case law regarding expert testimony offered in child sexual abuse litigation. PMID- 8435783 TI - Implications of developmental research for interviewing children. AB - This article first provides a brief review of recent research to update the investigative interviewer on children's development of cognition, memory and language. Next, we review results of studies which have focused on the development of children's specific knowledge about the legal system, and identify developmental and motivational factors which may influence children's willingness to report in legal settings. Next, clinical and research literature of young children's experience in pediatric settings offers ecologically compelling data for understanding children's reports of abusive touch, and strategies used for preparing children for medical procedures may be drawn on for preparation of children in sexual abuse cases. Finally, several issues are identified for future research. PMID- 8435784 TI - Overview: clinical identification of sexually abused children. PMID- 8435786 TI - Information processing of trauma. AB - This article presents a neuropsychosocial model to explain a victimization experience. It surveys the relation of sensation, perception, and cognition as a systematic way to provide a framework for studying human behavior and to describe human response to traumatic events. This framework is an information processing approach. The goal of information processing investigations is to identify how incoming external stimuli or intentionally engendered stimuli enter the central nervous system and eventuate in some kind of final response. PMID- 8435785 TI - Dissociative disorders in children: behavioral profiles and problems. AB - Transient dissociative episodes are a common and normative phenomenon during childhood that generally decrease during adolescence to relatively low levels in adults. Retrospective clinical research has firmly established a connection between childhood trauma and the development of dissociative disorders in adults. A growing number of clinicians are now identifying dissociative symptoms in abused children, and there is increasing evidence that dissociative disorders represent a significant and hitherto unrecognized form of psychopathology in traumatized children. Pathological dissociation is a complex psychobiological process that results in a failure to integrate information into the normal stream of consciousness. It produces a range of symptoms and behaviors including: (a) amnesias; (b) disturbances in sense of self; (c) trance-like states; (d) rapid shifts in mood and behavior; (e) perplexing shifts in access to knowledge, memory, and skills; (f) auditory and visual hallucinations; and (g) vivid imaginary companionship in children and adolescents. Many of these symptoms and behaviors are misdiagnosed as attention, learning or conduct problems, or even psychoses. Early identification and therapeutic intervention appear to be particularly efficacious in children in contrast to adults, although systematic studies of treatment and outcome are presently lacking. PMID- 8435787 TI - Sexual victimization and sexual behavior in children: a review of recent literature. AB - Empirical research pertaining to sexual behavior in sexually abused children, including record reviews, parent ratings, psychological assessment, self-report, and behavioral observation is reviewed and discussed. Sexual behavior is reported significantly more often in sexually abused children than nonabused children. However, the consistency of this finding varies with the research method. PMID- 8435788 TI - Epidemiological factors in the clinical identification of child sexual abuse. AB - The main finding from epidemiological literature on child sexual abuse is that no identifiable demographic or family characteristics of a child may be used to exclude the possibility that a child has been sexually abused. Some characteristics are associated with greater risk: girls more than boys, preadolescents and early adolescents, having a stepfather, living without a natural parent, having an impaired mother, poor parenting, or witnessing family conflict. Class and ethnicity appear not be associated with risk. In any case, none of these factors bear a strong enough relationship to the occurrence of abuse that their presence could play a confirming or disconfirming role in the identification of actual cases. PMID- 8435789 TI - Modern history of child sexual abuse awareness: cycles of discovery and suppression. AB - In the last century and a half, public and professional awareness of sexual abuse has emerged and been suppressed repeatedly. The 20th-century suppression of the problem has been linked to Freudianism, sexual modernism, and gender politics. Recent awareness of sexual abuse differs from awareness in the past because of the significant amount of current research attesting to the prevalence of sexual abuse and its injurious impact on human development. However, in the contemporary mental health professions, the courts, and the media, there has emerged an influential backlash against the latest discovery of child sexual victimization that utilizes arguments employed during earlier periods of suppression. Knowledge of the earlier cycles of discovery and suppression can assist professionals in understanding and countering present attempts to deny or minimize the problem of child sexual abuse. PMID- 8435790 TI - Sexual abuse of children in day care centers. AB - Sexual abuse of children in day care center settings has received considerable attention in the past decade. The nature and extent of allegations of sexual abuse in day care poses unique challenges to clinicians. Cases of sexual abuse in day care typically involve multiple victims and multiple perpetrators, and use of extreme threats to prevent disclosure. This article reviews the available research findings on the types of abuse known to occur in day care, the dynamics involved including the types of threats used to silence young victims, and patterns of disclosure. The impact of sexual victimization in day care on children and parents is discussed. Implications for the clinical evaluation of preschool-aged children in cases of suspected abuse in day care settings are presented. Developmental considerations related to psychosexual development and the development of memory and language are reviewed. Psychological defenses in repetitive trauma are discussed. PMID- 8435791 TI - Medical diagnosis of the sexually abused child. AB - This article reviews what has been learned in the last two decades about the medical diagnosis of child sexual abuse. Studies indicate that a normal physical exam is common in sexual abuse victims, that healing of injuries due to abuse is rapid and sometimes complete, that a minority of victims seen for abuse are boys, that nonsexual transmission of sexually transmitted diseases is rare, and that congenital and acquired conditions may mimic physical findings caused by sexual abuse. The article summarizes clinical research on physical findings in nonabused children, abused children, and abused children with independent confirmation of abuse. A classification of physical findings is proposed along a continuum of certainty that sexual abuse has occurred. The child's history is essential in the accurate diagnosis of most cases of sexual abuse. PMID- 8435792 TI - Electromyographic study of tensor and levator veli palatini muscles in patients with nasopharyngeal carcinoma. Implications for eustachian tube dysfunction. AB - BACKGROUND AND METHODS: To research the pathophysiology of the Eustachian tube (ET), electromyographies (EMG) of the tensor and levator veli palatini muscles (TVP and LVP) in 46 fresh specimens of nasopharyngeal carcinoma (NPC) were studied. RESULTS: Sixty-eight percent of the TVP on the symptomatic side had abnormal EMG. Normal EMG recordings were noted in all TVP on the asymptomatic side. The abnormal TVP EMG observed most often was poor interference pattern or decreased interference with swallowing, and not uncommonly, there were some abnormal motor unit action potentials of serrated or large polyphasic waveforms found on motor unit potential analysis. This is strong evidence of neurogenic abnormality of the TVP caused by the NPC invasion. Despite the large polyphasic or serrated action potentials often being recorded on the symptomatic sides of LVP, the abnormal EMG finding also was found in 12 LVP on the asymptomatic sides. CONCLUSIONS: There was no evidence that an ET dysfunction could be caused solely by an abnormal LVP function. This investigation and the study of ET function of these patients demonstrate that functional obstruction induced by the invasion of NPC to the nerve of TVP, rather than mechanical obstruction caused by the tumor mass effect on the ET, gives rise to the ear symptoms and signs of these patients. The authors suggest that the LVP action has little or no role in the function of the ET. PMID- 8435793 TI - Laminin distribution patterns are closely related to liver metastasis in gastric cancer. AB - BACKGROUND: Laminin is the major glycoprotein of basement membrane and is known to have an important role in the metastatic process. METHODS: The authors used immunohistochemical techniques to evaluate the distribution of laminin-containing basement membrane in specimens from 157 patients with advanced gastric cancer. RESULTS: This membrane was found less frequently in the deep periphery than in the mucosa. According to our classification of distribution patterns, 39 (24.8%) tumors had laminin in the mucosa and the deep periphery of tumor (Group A); 37 (23.6%) tumors had laminin in the mucosa but not in the periphery (Group B); and in 81 (51.6%) tumors laminin was not found in the mucosa or the periphery (Group C). Tumors with laminin in the deep periphery (Group A) were characterized by expansive growth (P < 0.05), and there was a significant correlation with the occurrence of vessel invasion (P < 0.05) and liver metastasis (P < 0.01). Patients with Group A tumors had poor prognosis compared with patients with Group C tumors (P < 0.05). Multivariate logistic regression analysis showed laminin distribution patterns to be an independent value for predicting liver metastasis, as are lymph node involvement and expansive growth. CONCLUSION: The authors propose that laminin-positive basement membrane in the deep periphery in gastric cancer tissue is a significant risk factor for liver metastasis. For such high risk patients, close follow up and postoperative adjuvant therapy are required. PMID- 8435794 TI - Diagnosis of primary early gastric lymphoma. Usefulness of endoscopic mucosal resection for histologic evaluation. AB - BACKGROUND AND METHODS: Eight patients thought to have primary early gastric lymphoma were studied to evaluate the usefulness of endoscopic mucosal resection for the diagnosis of reactive lymphoid hyperplasia (RLH) or malignant lymphoma. RESULTS: In these patients, conventional endoscopic forceps biopsy did not provide a definite histologic diagnosis. Endoscopic ultrasonography (EUS) demonstrated that the disease was limited to the mucosa and the submucosa in all patients, without any paragastric lymph node involvement, so endoscopic mucosal resection was performed to obtain specimens large enough to include the submucosa. As a result, primary early gastric lymphoma was diagnosed in five patients, for whom subsequent gastrectomy confirmed the diagnosis. CONCLUSIONS: The authors recommend that endoscopic mucosal resection be performed in patients thought to have primary early gastric lymphoma and for whom a definite diagnosis can not be made by conventional endoscopic forceps biopsy. PMID- 8435795 TI - Phase II evaluation of recombinant alpha-2a-interferon and continuous infusion fluorouracil in previously untreated metastatic colorectal adenocarcinoma. AB - BACKGROUND: Thirty-nine patients with advanced measurable metastatic colorectal carcinoma were entered in a clinical trial of recombinant alpha-2a-interferon (r alpha-2a-IFN) and continuous-infusion 5-fluorouracil (5-FU). Patients had not been treated previously with chemotherapy and had bidimensionally measurable disease. METHODS: A course of therapy consisted of a 5-day continuous infusion of 5-FU, 750 mg/m2/day, with r alpha-2a-IFN, 9 x 10(6) IU, subcutaneously, on days 1, 3 and 5 of the 5-FU infusion. A course of therapy was repeated every 15 days, and patients were examined for response after receiving four courses of therapy. RESULTS: One patient had a complete response, and 11 patients experienced partial responses, for an overall response rate of 31% (95% confidence interval [CI], 17 48%). The median duration of response was 7.5 months (range, 2-13 months). Fifty two percent of the patients entered in this trial are alive at time of this writing, with a median follow-up duration of 12.2 months (range, 6-24 months). Grade 3-4 toxicities included mucositis (nine patients), diarrhea (two patients), granulocytopenia (two patients), and fatigue (three patients). CONCLUSION: This regimen of 5-FU with r alpha-2a-IFN administration does not appear to be superior to previously published schedules of 5-FU with r alpha-2a-IFN or to other methods that modulate 5-FU. PMID- 8435796 TI - Thymic carcinoma. A distinct clinical entity responsive to chemotherapy. AB - BACKGROUND: Thymic carcinomas are rare tumors of the anterior mediastinum. These tumors are distinct thymic neoplasms that differ from their more common counterpart, thymoma. As opposed to thymomas, thymic carcinomas are histologically malignant neoplasms with a clinical course that tends to be much more aggressive than that of patients with thymoma. METHODS: Between 1984 and 1990, five patients with thymic carcinoma treated with cisplatin-based combination chemotherapy were seen at Indiana University Hospital. These patients' diagnoses, courses, and treatments were reviewed. RESULTS: Three patients responded (two completely) to cisplatin-based chemotherapy. CONCLUSIONS: This form of chemotherapy merits additional study in such patients, and our experience indicates that at least some will have clinically meaningful responses. The optimum regimen is unclear, but would contain cisplatin and probably should be similar to that used in germ cell tumors. PMID- 8435798 TI - Crystalglobulinemia syndrome. A manifestation of multiple myeloma. AB - BACKGROUND: Crystalglobulinemia syndrome (CS) is a rare vasculopathy that may arise as a complication of multiple myeloma (MM). METHODS AND RESULTS: A patient with multiple myeloma in whom crystalglobulinemia syndrome was the initial manifestation with polyarthralgias, cutaneous ulceration, and lower limb ischemia requiring bilateral amputations is reported. CONCLUSION: The rare syndrome of crystalglobulinemia may be associated with multiple myeloma, so it is important that clinicians be aware of this syndrome and its clinical and morphologic features. PMID- 8435797 TI - Prognostic significance of serum alkaline phosphatase measurements in patients with osteosarcoma treated with adjuvant or neoadjuvant chemotherapy. AB - BACKGROUND: It is known that many patients with osteosarcoma have high serum alkaline phosphatase (SAP) levels. The prognostic significance of this finding, however, is still controversial. METHODS: The pretreatment SAP levels of 656 patients with osteosarcoma of the extremities (107 metastatic and 549 localized at presentation) were examined to evaluate whether the enzyme levels had a clinical value in predicting the course of the disease. RESULTS: The percentage of patients with increased SAP levels was significantly higher in the metastatic group than in the group of patients with localized disease (91.5% versus 61.3%; P < 0.001). In the latter group, treated with adjuvant and neoadjuvant chemotherapy, the relapse rate was significantly higher in patients with elevated pretreatment SAP levels than in those with normal levels (55.1% versus 26.4%; P < 0.001). Among patients with elevated SAP levels, the percentage of relapses was higher in patients with high levels of the enzyme in comparison with patients with moderately elevated values (66.4% versus 47%; P < 0.05). After treatment, SAP levels almost always return to normal values, and a correlation between postoperative levels of the enzyme and prognosis could not be made. CONCLUSIONS: These data demonstrate that in osteosarcoma of the extremities, pretreatment SAP levels have a prognostic value and they should be considered when comparing the results achieved with different therapeutic protocols and in planning new randomized clinical trials. PMID- 8435799 TI - Clinically unsuspected Hodgkin disease presenting initially in the bone marrow of patients infected with the human immunodeficiency virus. AB - BACKGROUND: Hodgkin disease (HD) in patients infected with the human immunodeficiency virus (HIV) is an aggressive neoplasm that often exhibits high stage and extranodal involvement at the time of presentation. Because of the propensity of HIV-associated HD to involve the bone marrow early in the course of the neoplasm, bone marrow examination may often represent the initial source for the diagnosis. In most cases, however, there is a clinical suspicion of HD before bone marrow examination. METHODS: Three cases are presented in which HD was not clinically suspected and the initial diagnosis of the neoplasm was suggested by atypical lymphohistiocytic lesions identified on routine bone marrow examination, later to be confirmed by lymph node biopsy. RESULTS: In none of the cases was HD clinically suspected before bone marrow examination; in two cases, fever was the only clue that the patients may have HD. It was found on bone marrow biopsy that all three patients had lymphohistiocytic aggregates with large atypical mononuclear cells suggestive but not diagnostic of HD. CONCLUSIONS: Bone marrow examination may provide the initial evidence of HD in HIV-infected patients, even when there is little or no clinical indication of the neoplasm. PMID- 8435800 TI - The prognosis of patients with stage III melanoma. Prospective long-term study of 286 patients of the Fachklinik Hornheide. AB - BACKGROUND: Prognostic factors for patients with stage III melanoma are still controversial. METHODS: Two hundred eighty-six patients with solitary cutaneous malignant melanoma of the skin in Stage III (International Union Against Cancer [UICC]) were followed up for as long as 11 years. RESULTS: Patients in risk group pT 4a, pN O (primary tumor thickness of more than 4 mm or invasion of subcutis and absence of regional lymph node metastasis in elective lymph node specimen) have a 5-year survival rate of 72.8%. If regional metastases are excluded clinically (pT 4a, NO), the 5-year survival rate is 62.8%. Patients with regional lymph node metastases have an average 5-year survival rate of 39%, depending mainly on the number of involved lymph nodes and the depth infiltration of the primary tumor. The number of involved lymph nodes reflects the grade of dissemination. It shows a stronger correlation with the prognosis than does the size of metastases. CONCLUSIONS: The authors recommend that revisions of the UICC classification should distinguish Stage IIIA and IIIB based on the presence or absence of regional metastases and that a clearer distinction should be made between regional cutaneous or subcutaneous metastases and regional lymph node metastases. PMID- 8435801 TI - Malignant peripheral nerve sheath tumors. A clinicopathologic study of 28 cases. AB - BACKGROUND: In order to improve management, the files and tissue sections of 28 cases of malignant peripheral nerve sheath tumors (MPNST) diagnosed at the University of Virginia Health Sciences Center between 1960 and 1990 were reviewed. METHODS: Clinical data tabulated included age, sex, race, the presence or absence of von Recklinghausen neurofibromatosis type 1 (NF-1), tumor size, tumor location, type of treatment, and status of surgical margins. Pathologic study included assessment of mitotic rate, divergent differentiation, cellular atypia, necrosis, and vascular reaction. RESULTS: The median disease-free survival time was 11 months, and the median overall survival time was 44 months. Overall survival and disease-free survival were significantly influenced by patient age, tumor location, tumor size, extent of surgery, and quality of margins. Patients with a family history of neurofibromatosis also had better disease-free survival. None of the other clinical variables correlated with survival. CONCLUSIONS: The authors recommended that patients with NF-1 be followed closely for MPNST development. For most cases, treatment should include aggressive surgery with wide surgical margins combined with adjuvant radiation therapy. Chemotherapy may have a role for treatment failures. PMID- 8435802 TI - Phase II trial of carboplatin and etoposide in metastatic breast cancer. AB - BACKGROUND: High-dose chemotherapy with hematopoietic support produces high rates of response in metastatic breast cancer. To facilitate new high-dose regimens there is a need to identify active agents with toxicity limited to hematopoietic suppression. Cisplatin/etoposide is a highly active regimen in metastatic breast cancer, but cisplatin dose-escalation is limited by nonhematologic toxicity. Carboplatin is active in breast cancer and has marrow-dominant toxicity. Demonstration of activity for the combination of carboplatin and etoposide would facilitate their inclusion in high-dose programs. METHODS: A single treatment arm prospective Phase II study in patients with measurable or evaluable breast cancer was done. RESULTS: Forty-six patients with metastatic breast cancer were treated with the combination of carboplatin and etoposide. Among 19 patients without prior chemotherapy, one complete and seven partial responses were observed, for an objective response rate of 42% (95% exact confidence intervals [CI], 20-67%). One partial response was seen among 12 patients with prior chemotherapy limited to the adjuvant setting. No responses were seen among 14 patients who had received prior chemotherapy for metastatic cancer. Two treatment-related deaths occurred, both attributable to sepsis. One patient returned to her community for treatment after receiving one course of protocol therapy before response assessment and could not be studied for response. CONCLUSION: The activity observed with this regimen in patients with no prior chemotherapy coupled with its potential for dose escalation suggests a possible role in high-dose programs with hematopoietic support. The inactivity of the combination in patients with prior therapy for metastatic breast cancer indicates that there is no advantage to its use in the salvage setting. PMID- 8435803 TI - Breast cancer risk associated with proliferative breast disease and atypical hyperplasia. AB - BACKGROUND: Women with proliferative breast disease (PD) have been observed to have an increased risk of breast cancer. The authors evaluated the effect of PD on breast cancer risk in a case-control study among participants of the Breast Cancer Detection Demonstration Project (BCDDP). METHODS: More than 280,000 women were screened in the BCDDP at 29 centers. Study subjects were selected from BCDDP participants who underwent biopsy that revealed benign breast tissue. There were five BCDDP centers for which histologic slides were available on more than 85% of the benign biopsy specimens. Case patients for this study were the 95 women from these five centers who had breast cancer develop during follow-up. Two matched control patients who did not have breast cancer develop were selected for each case. The biopsy slides were reviewed by two pathologists who were blinded with regard to cancer outcome. RESULTS: Women with atypical hyperplasia (AH) had 4.3 times the breast cancer risk of women without PD (95% confidence interval [CI], 1.7-11). In women with PD lacking AH, the relative risk was 1.3 (95% CI, 0.77 2.2). A family history of breast cancer (FH) increased breast cancer risk 2.4 times (95% CI, 1.4-4.3). The joint occurrence of FH and AH had a strong synergistic effect on breast cancer risk. CONCLUSIONS: AH is a reliable marker of increased breast cancer risk among women undergoing breast biopsy. PMID- 8435804 TI - Population-based cohort investigations of the risk for malignant tumors in first degree relatives and wives of men with breast cancer. AB - BACKGROUND: Retrospective studies of familial cancer risks could be subjected to bias and should be supplemented with prospective studies if possible. Few such studies exist, and no prospective population-based study has addressed the risk for malignant tumors among relatives or wives of men with breast cancer. METHODS: All first-degree relatives and wives of 153 men whose conditions were diagnosed as male breast cancer from 1965 to 1989 in the southern health-care region of Sweden were identified through parish data. Relatives and wives alive January 1, 1958, were included in two cohorts. Their vital status and cancer morbidity were studied in the Swedish Cancer Registry, Cause of Death Registry, and Census Registry. RESULTS: The incidence for malignant tumors was significantly increased among female first-degree relatives (standardized morbidity ratio [SMR], 1.36). Significantly elevated SMR were seen for breast carcinoma (SMR, 1.80), ovarian carcinoma (SMR, 2.27), and cancer of the parotid gland (SMR, 5.58). Elevated nonsignificant SMR were seen for cancer of the cervix uteri and for bone and soft tissue sarcoma. An almost significant decreased overall cancer incidence was seen for male first-degree relatives (SMR, 0.75). The most pronounced decrease was seen for cancer of the prostate. The increased breast cancer incidence in female relatives were present in mothers, sisters, and daughters. The overall tumor incidence was not increased (SMR, 0.98) in wives of men with breast cancer. There was no significant increase in breast cancer incidence (SMR, 0.97). CONCLUSIONS: Female first-degree relatives of men with breast cancer have an elevated incidence of breast cancer and other female genital tumors, whereas male first degree relatives have a reduced cancer incidence. Wives of men with breast cancer have a similar cancer incidence as the general population. PMID- 8435805 TI - Mass screening for endometrial cancer directed in risk groups of patients with diabetes and patients with hypertension. AB - BACKGROUND: The interest in mass screening programs for the early detection of endometrial cancer (EC) has grown with the rising incidence of this disease. Preliminary programs directed at asymptomatic women with only one risk factor, i.e. age, have not been cost-effective. METHODS: In the current study, 597 asymptomatic women from 45-69 years of age with diabetes and/or hypertension were screened by Vabra (Berkeley Medevices Inc., Berkeley, CA) aspiration. RESULTS: Among the women with diabetes, 6.3% preinvasive lesions of the endometrium were found. This is significantly more than the rate among women with hypertension, which was 1.3% (P < 0.01). CONCLUSIONS: Regular mass screening programs for the early detection of EC should be directed at asymptomatic diabetic women 45 years of age or older. This study does not indicate that similar screenings would be effective for women with hypertension. PMID- 8435806 TI - DNA and S-phase fraction analysis by flow cytometry in prostate cancer. Clinicopathologic implications. AB - BACKGROUND: Available prognostic factors for prostate cancer have not been proven consistently useful. The authors evaluated the prognostic value of DNA analysis by flow cytometry (FCM) in prostate cancer. METHODS: Paraffin-embedded tumor specimens taken at tru-cut biopsy or transurethral resection (TURP) from 81 patients with prostate cancer were analyzed for DNA content and S-phase fraction (SPF) by FCM according to the method of Hedley et al (1983). RESULTS: Thirty-five of the 63 (55.5%) evaluable DNA histograms had a diploid pattern, 18 (28.5%) a distinct aneuploid peak, and 10 (16%) a tetraploid pattern. An association was established between DNA ploidy abnormalities and Gleason score (P < 0.04) or presence of metastases at diagnosis (P < 0.0002). At Kaplan-Meier analysis, overall survival was significantly longer (P < 0.0002) in patients with diploid than in those with nondiploid tumors. Among patients with different risk categories, i.e. tumor size, Gleason score, and metastases at presentation, ploidy improved the detection of patients with poorer survival, with the exception of those with T1-T2 tumors. Cox regression analysis showed that ploidy was significantly related to survival. Bivariate models containing ploidy and SPF or Gleason score had a predictive value similar to that including all variables. CONCLUSION: The study data show that DNA ploidy provides additional prognostic information in patients with locally advanced or metastatic prostatic cancer. The role of SPF remains to be established. PMID- 8435807 TI - Prognostic significance of bone metastases in patients with metastatic prostate cancer. AB - BACKGROUND: The distribution of bone metastases on a bone scan has not been duly considered when assessing the prognosis of metastatic prostate cancer. METHODS: The medical records of 76 patients with newly diagnosed, untreated metastatic prostate cancer were reviewed. According to the distribution of bone metastases on the initial bone scan, we divided the patients into three groups: Group I (having bone metastases exclusively within the pelvis and the lumbar spine), Group II (having bone metastases exclusively outside these bones), and Group III (having bone metastases in both areas). RESULTS: Among the responders to androgen deprivation, those in Group I survived significantly longer than did those in Groups II or III. Because the extent of the disease and the distribution of histologic differentiation in Groups I and II were similar, the results indicate that the presence of bone metastases outside the pelvis and the lumbar spine is predictive of short survival time. This prediction was not possible when the extent of disease (EOD) grading system was used. CONCLUSION: The distribution of bone metastases on the initial bone scan should be considered as a variable for the prognostic stratification of patients with metastatic prostate cancer. PMID- 8435808 TI - Filamentous degeneration of neurons. A possible feature of cytosine arabinoside neurotoxicity. AB - BACKGROUND: The use of high-dose cytosine arabinoside (Ara-C) may be complicated by a characteristic form of cerebellar neurotoxicity. Other reported manifestations of neurologic dysfunction include signs of possible cranial neuropathies, for which a neuropathologic substrate has not been previously reported. METHODS: A 43-year-old man was treated for refractory acute promyelocytic leukemia with a regimen of high-dose Ara-C. He died after dysarthria, ophthalmoplegia, and severe cerebellar neurotoxicity developed. RESULTS: The postmortem examination revealed a peculiar subacute neuronopathy that involved preponderantly brain stem tegmental and spinal motor neurons. The neuronopathy was characterized by hypereosinophilic perikarya and karyolytic nuclei. The perikaryal changes resulted from accumulations of argyrophilic masses of filaments that stained positively with neurofilament antibodies and ultrastructurally were shown to be composed of bundles of intermediate filaments. CONCLUSIONS: This report indicates that Ara-C neurotoxicity, possibly aggravated in our patient by oliguric renal failure, is not confined to the cerebellum but involves cranial nerve and spinal motor neurons, which in turn may explain the cranial neuropathies that sometimes complicate the use of high-dose Ara-C therapy. PMID- 8435809 TI - Patient use of treatment-related information received from the Cancer Information Service. AB - This study explored patient information-seeking behavior and how such behavior might affect patient-physician interaction or health-care decisions. Telephone interviews were conducted with 257 patients with cancer and their relatives who called the National Cancer Institute's Cancer Information Service (CIS) and who received treatment-related information. Results indicated that these patients were generally very satisfied with communication from their treating physicians, had strong information needs, and preferred to participate in their treatment plans. They sought information from CIS just after diagnosis (49%) or during treatment (31%). Many of these patients (42%) discussed the CIS information with their physicians and 19% of these physicians sought more information or consulted a CIS referral. CIS referrals were contacted personally by 18% of patients. Stepwise discriminant analyses indicated that, compared with patients who did not, patients with either of these outcomes were more stressed by their disease and had been seen at more hospitals. Additionally, patients who shared CIS information with their physicians were also younger and more trusting that their physicians had current knowledge. Patients who themselves contacted a CIS referral were also more educated, had higher information needs, were less satisfied with the clarity of physicians' answers to their questions, called CIS earlier in their illness, and called specifically for a referral. Overall, these patients' most common information needs were for exploring all treatment options and being knowledgeable when discussing treatment plans with physicians. The information received from CIS satisfied these needs and was often communicated to their physicians. PMID- 8435810 TI - Pulmonary metastases in children and young adults with differentiated thyroid cancer. AB - BACKGROUND: The prognostic significance and optimal care of children with differentiated thyroid cancer and pulmonary metastases are not well established. METHODS: Of 209 patients younger than 25 years of age who were treated at University of Texas M. D. Anderson Cancer Center between 1960 and 1990 and for whom there was sufficient information, 19 (9%) had pulmonary metastases at presentation. RESULTS: All of these patients had regional lymphadenopathy at the time of diagnosis. All but two had intense, diffuse radioiodine uptake in the lungs; there were two false-negative scans immediately after surgical procedure caused by competing thyroid residual. The chest radiograph (CXR) was normal in 8 of 17 (42%) patients with abnormal radioiodine scans. After therapy with radioiodine (100-499 mCi), CXR appeared normal in 7 of 9 patients with initial abnormal radiographs (within 6-75 months). Radioiodine uptake by the lungs normalized in 3 of 8 patients with initially normal radiographs, and in 3 of 9 patients with initially abnormal radiographs. There have been no deaths in these 19 patients. CONCLUSION: Pulmonary metastases are not uncommon in children and young adults with differentiated thyroid cancer, especially those who have regional lymphadenopathy. The lung metastases almost always concentrate radioiodine diffusely and may be associated with a normal CXR in almost half of the patients. Pulmonary metastases may be overlooked unless near total thyroidectomy is followed by total body radioiodine scan (TBS) in all children and young adults who have regional lymphadenopathy of the neck. PMID- 8435811 TI - Long-term follow-up for brain metastases treated by percutaneous stereotactic single high-dose irradiation. AB - Surgery is considered the treatment of choice for solitary brain lesions, and radiation therapy is indicated for metastases only in vital or sensitive regions that cannot be excised without risk of disabling neurologic defects. In these cases, radiosurgery may be an alternative to conventionally fractionated radiation therapy. At the Heidelberg linear accelerator-based radiosurgery facility, 69 patients were treated for 102 inoperable brain metastases. The primary tumor sites included non-small cell lung carcinoma (n = 24), renal cell carcinoma (n = 14), melanoma (skin) (n = 14), colorectal carcinoma (n = 6), carcinoma of unknown primary (n = 4), and others (n = 7). Eleven patients were treated for relapse after surgery or after conventional whole-brain irradiation. The doses at the isocenter varied from 15-50 Gy (mean, 21.5 Gy). Ten patients with multiple metastases received a planned combination of whole-brain irradiation plus a single boost of 15 Gy. The median survival time for the entire group was 6 months, with a 1-year-survival of 28.3%. Factors associated with significant improvement of survival were brain metastases without other metastatic disease and good response to radiation therapy. Five of 22 patients (22.9%) with metastases located only in the brain survived longer than 2 years. An improvement in neurologic function was found in 81% within a period of 3 months. With imaging techniques, complete remission was found in 20%, partial remission in 35%, stable disease in 40%, and relapse in 5%. The authors concluded that radiosurgery is an effective and safe therapy for brain metastases. It can be applied as primary treatment, as boost in combination with whole-brain irradiation, or as treatment for patients with relapse in a previously irradiated field. PMID- 8435813 TI - Molecular aspects of tumor cell invasion and metastasis. PMID- 8435812 TI - Improved survival duration in patients with unresected solitary brain metastasis using accelerated hyperfractionated radiation therapy at total doses of 54.4 gray and greater. Results of Radiation Therapy Oncology Group 85-28. AB - BACKGROUND: Although there have been occasional reports of improved response with greater doses of irradiation for unresected brain metastases, dose escalation has not been systematically studied in a cohort of patients with solitary brain metastasis. The current study examines this group of patients to evaluate dose escalation using accelerated hyperfractionated radiation therapy (XRT) with regard to survival, patterns of failure, and toxicity. METHOD: Radiation Therapy Oncology Group (RTOG) 85-28, a Phase I/II randomized trial of accelerated hyperfractionated XRT for patients with unresected supratentorial brain metastases, enrolled 153 patients with solitary brain metastasis. Whole brain dose was 32 Gray (Gy) administered in 1.6 Gy fractions twice a day with an interfraction interval of 4-8 hours. Boost dose was escalated to total doses of 48.0, 54.4, 64.0, and 70.4 Gy. RESULTS: Acute and late toxicities were acceptable. The median survival time and 1-year survival rates were 4.9 months and 20% at 48 Gy; 5.4 months and 33% at 54.4 Gy; 7.2 months and 28% at 64 Gy; and 8.2 months and 37% at 70.4 Gy, respectively. Comparison of the upper three dose treatment arms to the 48 Gy treatment arm revealed a superior survival time with doses of 54.4 Gy and greater (P = 0.05). Improvement in neurologic function appeared to increase with dose escalation, with 25% of patients experiencing improvement at doses of 48 Gy, 38% at 54.4 Gy, 50% at 64 Gy, and 63% at 70.4 Gy (P = not significant). CONCLUSION: A radiation dose response for survival time appears to exist with the use of accelerated hyperfractionated XRT for patients with unresected solitary brain metastasis. PMID- 8435814 TI - Thromboembolism in cancer. Changing trends. AB - The multitude of classic manifestations of paraneoplastic thromboembolism (TE), including new aspects, are reviewed. This emphasizes the complexity of the situation that the physician faces in dealing with paraneoplastic TE. Unexplained TE may serve as a hint for the presence of a hidden tumor. However, efforts to uncover such an underlying malignancy often are unrewarding. The view has been expressed that it is inappropriate to conduct an extensive search for an occult neoplasm unless there are more specific indications. A recent study defined clues that might separate patients with TE and occult cancer from those unaffected by a malignant neoplasm. The study of the hemostatic alterations in patients with cancer underscores the triple role of cancer cells in the pathogenesis of TE: injury to the endothelial lining of blood vessels, activation of platelets, and activation of blood coagulation and depression of anticoagulant functions. The failure of standard anticoagulant treatment in many instances is better understood. Novel approaches to treatment include low-molecular-weight heparin(s) for long-term administration or, alternatively, the initial placement of a Greenfield filter in the vena cava instead of anticoagulant therapy. Either of these may provide superior results in comparison to standard heparin treatment. PMID- 8435815 TI - The Cooperative Human Tissue Network. An update. AB - BACKGROUND: During the past decade, the National Cancer Institute became aware of a lack of availability of human tissues for research, especially in the fields of molecular biology, genetics, and immunology. METHODS: In 1987, the National Cancer Institute (NCI) established the Cooperative Human Tissue Network (CHTN) by funding three institutions that had extensive experience in the procurement and distribution of tissues for research. RESULTS: Since its inception, the CHTN has been expanded to five member institutions, with the addition of the Columbus Children's Hospital (the Pediatric Division for the procurement of pediatric tissues) and Case Western Reserve University. Each of the five divisions have established regional networks of institutions that supply tissues to the major divisions. From 1987 through 1991, the CHTN has distributed more than 29,000 human tissue samples and supplied approximately 500 researchers throughout the country. CONCLUSIONS: This report describes the development and current status of the CHTN, a valuable resource to the research community. PMID- 8435816 TI - Sudden cardiac death. Magnitude of the problem, substrate/trigger interaction, and populations at high risk. AB - Sudden cardiac death continues to be a major clinical and public health problem. Prospective identification of patients at high risk for cardiac arrest is difficult, being limited by the large size of the population subgroups that contain the majority of victims of sudden cardiac death and by the time dependence of risk of sudden death. Pathophysiologically, sudden cardiac death can be viewed as an interaction between structural abnormalities of the heart, transient functional disturbances, and the specific electrophysiologic events responsible for fatal arrhythmias. Further understanding of the dynamics of high risk populations and mechanisms of sudden death may lead to effective measures for control of risk. PMID- 8435817 TI - Classification and terminology of supraventricular tachycardia. Diagnosis and management of the atrial tachycardias. AB - This article describes some of the historical approaches to classifying supraventricular tachycardias and the evolution of the nomenclature as the knowledge of tachycardias improved. A classification scheme that is mechanistically based and favored by the authors, diagnostic criteria, clinical presentation, and therapy of the atrial tachycardias is also presented. PMID- 8435818 TI - Work-up and management of sudden cardiac death survivors. AB - Management of patients resuscitated from an out-of-hospital cardiac arrest can be divided into three phases: (1) the in-hospital phase primarily deals with treatment of the cardiac, pulmonary, and neurologic complications of the resuscitation; (2) the second phase consists of diagnostic studies to identify any underlying cardiac pathology or predisposing factors and to characterize the nature of the patient's arrhythmia; and (3) in the final phase, these data are used to guide the appropriate choice of therapy. PMID- 8435819 TI - A functional approach to the preexcitation syndromes. AB - Electrophysiologic studies have been used to elicit the mechanisms of the preexcitation syndromes and have become a therapeutic tool over the past decade. A thorough understanding of the physiology and anatomy of accessory pathways that are responsible for preexcitation and the associated arrhythmias is necessary before considering the various forms of intervention. The approach to patients with preexcitation syndromes is discussed, with an emphasis on the functional properties of accessory pathways and the associated arrhythmias. PMID- 8435820 TI - Atrioventricular nodal reentrant tachycardia. Electrophysiologic characteristics, therapeutic interventions, and specific reference to anatomic boundary of the reentrant circuit. AB - Over the past several decades there has been enormous progress in the understanding of many electrophysiologic characteristics of the AVNRT circuit. Although a great number of questions have been resolved, several pertinent issues require further investigation. Medical treatment remains the most widely used therapeutic intervention for acute or short-term management of patients with recurrent AVNRT. However, nonpharmacologic approaches, particularly transcatheter modification of the AV node, have increasingly become popular for long-term management. Radiofrequency energy has been safe and effective for transcatheter ablative techniques. It seems highly likely that in the next several years, selective transcatheter ablation of the AV nodal (slow or fast) pathway, by providing permanent cure, will become the modality of choice in symptomatic patients with AVNRT. PMID- 8435821 TI - Neurocardiogenic syncope. Diagnosis, mechanisms, and treatment. AB - Neurocardiogenic syncope is a common medical problem that can be identified easily by history and the findings of the head-up tilt test. Depressor reflexes from the heart causing sympathetic withdrawal that, in turn, lead to peripheral vasodilatation and hypotension may have an important role in the pathogenesis of neurocardiogenic dysfunction. Once a diagnosis of neurocardiogenic syncope has been made, specific therapeutic strategies can usually prevent recurrent syncope. However, the natural history of neurocardiogenic syncope has not been studied. Double-blind placebo-controlled studies or drug withdrawal trials are needed to assess whether all patients with neurocardiogenic syncope need lifelong therapy. PMID- 8435822 TI - Work-up and management of patients with sustained and nonsustained monomorphic ventricular tachycardias. AB - The approach to patients with hemodynamically-stable sustained monomorphic ventricular tachycardia (VT) must be individualized. The clinical outcome is critically dependent on the type and degree of underlying heart disease, symptoms at presentation, inducibility at electrophysiology study, and responses to antiarrhythmic drugs. Various methods for assessing therapeutic efficacy and both pharmacologic and nonpharmacologic therapies are discussed. The majority of patients with nonsustained VT have no symptoms directly attributable to this arrhythmia that is associated with an increased risk for sudden death in certain patients with coronary artery disease and hypertrophic cardiomyopathy. The optimal means to prophylax against sudden death in these patients is not presently clear, but prospective trials are underway to evaluate this problem. PMID- 8435823 TI - Evaluation and management of patients with polymorphic ventricular tachycardia. AB - This article reviews the current understanding of the mechanisms for polymorphic VT, its clinical manifestation, and therapies. The various idiopathic long QT syndromes and acquired forms of this entity are addressed, and a new syndrome of polymorphic VT associated with a normal heart and normal QT interval is emphasized. PMID- 8435824 TI - Identification of patients with high risk of arrhythmic mortality. Role of ambulatory monitoring, signal-averaged ECG, and heart rate variability. AB - This article discusses the roles of 24-hour ambulatory Holter monitoring, left ventricular function, the signal-averaged electrocardiogram (ECG), and heart rate variability for identification of high risk patients following myocardial infarction. Because these noninvasive tests have low positive predictive value, a combination of noninvasive tests is recommended for risk stratification. PMID- 8435825 TI - Pharmacologic therapy in patients with ventricular tachyarrhythmias. AB - Table 5 can be used as framework for a summary of the previous discussion on pharmacologic therapy for ventricular tachyarrhythmias. The system for grading the severity of symptoms of ventricular tachyarrhythmias, previously presented in Table 3, is arranged vertically along the left side of Table 5. Horizontally across the top, patients are grouped according to the presence or absence of structural heart disease, and those with structural heart disease are further dichotomized according to left ventricular ejection fraction. As can be seen, patients with class I symptoms should not be treated whenever possible, although in patients with reduced left ventricular function (especially coronary heart disease), an argument can be made for empirical treatment with beta-adrenoceptor blocking agents whenever possible. Patients with class II symptoms can be treated empirically with beta-adrenoceptor blocking agents. Other antiarrhythmic agents may be safer when there is no underlying structural heart disease, but this has not been proved. The use of antiarrhythmic agents other than beta-adrenoceptor blocking agents in patients with class II symptoms should probably be guided and monitored by ambulatory electrocardiographic recording and exercise tolerance testing. In the patient with hemodynamically stable ventricular tachycardia, electrophysiologic-guided therapy is probably preferable whenever possible. Encainide, flecainide, and similar drugs should be avoided when there is a possibility of residual ventricular premature depolarizations of three or more per hour. Some uncertainty remains concerning the treatment of patients with class III and class IV symptoms and no structural heart disease. Some patients may fall into a specific group that is very responsive to drug therapy. These patients should probably be treated like other patients with class III and class IV symptoms. Electrophysiologic testing may be helpful. When such patients have a reproducibly induced sustained ventricular tachyarrhythmia, it is likely that antiarrhythmic drug therapy will render the arrhythmia noninducible, and that they will do well while receiving long-term pharmacologic therapy. When such patients do not have a reproducibly induced sustained ventricular tachyarrhythmia, the main controversy is whether therapy is needed. If it is decided that such a patient needs therapy, the choice is usually between empiric amiodarone and an ICD, although catheter ablation may be helpful in selected instances. Patients with class III and class IV symptoms who have structural heart disease require therapy. Although this continues to be an evolving area of investigation, for many of these patients, the initial attempt at therapy should be pharmacologic.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8435826 TI - Nonpharmacologic therapies in patients with ventricular tachyarrhythmias. Catheter ablation and ventricular tachycardia surgery. PMID- 8435827 TI - Implantable cardioverter-defibrillator therapy for prevention of sudden cardiac death. AB - Patients with known symptomatic VT or VF are at high risk for sudden cardiac death. Various therapeutic choices can be used to reduce the incidence of arrhythmic sudden cardiac death. These include beta-blockers, class I and III antiarrhythmic agents, VT focal ablations, and ICD therapy. The overall incidence of sudden cardiac death in ICD recipients is less than 2% per year, a rate of survival not achieved with any of the available antiarrhythmic agents. VT surgical therapy can produce comparable survival results, but the minimal operative mortality is higher than that with ICD therapy. In patients with noninducible VT/VF or inducible polymorphic VT, and in those refractory to or intolerant of antiarrhythmic agents and poor left ventricular function, ICD therapy may be the only realistic option. PMID- 8435828 TI - Cardiovascular and interventional radiology--the German perspective. PMID- 8435829 TI - Fine needle biopsy without syringe aspiration. AB - Aspiration biopsies of fresh disease-free bovine hepatic liver were performed with three commercially available, small-gauge biopsy needles. A syringe was used to create a negative pressure when using Chiba and Sure-cut needles. A syringe was not used when using PercuCut needles which create an internal negative pressure equivalent to a 1.5 ml syringe when the stylet is partially withdrawn. The PercuCut and Chiba needle yielded a significantly larger specimen size than the Sure-Cut needle. There was no significant difference in sample size between the PercuCut and Chiba needles. All samples were of diagnostic quality. PMID- 8435830 TI - Transcatheter arterial infusion therapy combined with radical hysterectomy in the treatment of advanced cervical cancer. AB - Two or three sessions of transcatheter arterial infusion (TAI) therapy were performed preoperatively in 13 patients with advanced cervical cancer (stage 3 or more). The efficacy of TAI was evaluated by tumor markers, magnetic resonance imaging (MRI), and postoperative histopathological examination. In all cases, tumor marker levels decreased after TAI therapy, and MRI also showed a decrease in the tumor size in 11/12 patients. The tumor tissue resected at radical hysterectomy showed no viable cancer cells in 6 patients, and no viable extrauterine cancer was detected in 5 more patients. Thus, TAI performed via both internal iliac arteries reduced both tumor size and extension to the parametrium, and it appears to have the potential to be an effective treatment modality for advanced cervical cancer. PMID- 8435831 TI - Rapid three-dimensional surface reconstruction of magnetic resonance images of large arteries and veins: a preliminary evaluation of clinical utility. AB - We have implemented a computerized system for relatively rapid (< 1 h) three dimensional (3D) surface rendering of flow-sensitive (gradient refocused) magnetic resonance images. The method has been applied in 8 patients with six different clinical problems and was found to enhance understanding of normal and abnormal aortic, caval, and portosystemic venous anatomy. 3D images are useful for communicating complex anatomic information and may help with difficult diagnoses. Advantages and limitations of the present system are discussed. PMID- 8435832 TI - In vitro flow phantom analysis and clot-capturing ability of incompletely opened Vena Tech-LGM vena caval filters. AB - It has been shown recently that Vena Tech-LGM (B. Braun Vena Tech, Evanston, IL) filters inserted into the inferior vena cava via the jugular route may be deployed sometimes in an incompletely opened (IO) position. The flow characteristics and clot capturing ability of IO Vena Tech-LGM filters are not clearly understood. Using a vena cava flow phantom, the clot-capturing abilities of the IO and opened Vena Tech-LGM filters were assessed. For 5 x 5-mm clots, the IO Vena Tech-LGM filter captured only 40% of thrombi compared with a 90% capture rate for the opened filter. The capture rates were 90 and 100% for the IO and opened filter, respectively, for larger 5 x 15-mm clots. It was found that the IO filter could capture 2-7 x 25 mm thrombi prior to the development of a turbulent bypass channel which prevented subsequent clot capture. Using 5 x 15 mm clots, this same phenomenon occurred with the capture of 6 and 11 thrombi by the IO and opened Vena Tech-LGM filters, respectively. Our results suggest a significantly reduced filtering efficiency for the IO Vena Tech-LGM device. However, there is a high rate of clot capture with the opened Vena Tech-LGM filter. PMID- 8435833 TI - STIR imaging of synthetic vascular graft infection. AB - Nine patients with suspected prosthetic vascular graft infection were studied with axial spin echo (SE) and short TI inversion recovery (STIR) magnetic resonance imaging. Images were assessed for presence and extent of abnormality. All patients had either surgical (8/9) or bacteriologic (6/9) confirmation of infection. STIR images better defined the extent of infection and had greater fat fluid contrast than SE images in 6/9 studies. In 3 cases with peri-graft fluid alone, T2-weighted images had slightly greater contrast, although the STIR images were still diagnostic. STIR imaging can offer improved accuracy in evaluation of suspected prosthetic graft infection when used in conjunction with SE techniques. PMID- 8435834 TI - Percutaneous transluminal aortic angioplasty: early and late results. AB - Percutaneous transluminal angioplasty of the infrarenal abdominal aorta (13 patients) and its bifurcation (15 patients) was performed in 28 patients with a total of 32 dilatation procedures. The group consisted of 16 female and 12 male patients and initial successful dilatation was achieved in all. Recurrence within 1 month requiring bypass surgery occurred in 1 patient. Three patients were lost to follow-up. Long-term follow-up in the remaining 24 patients ranged from 1 to 9 years with a mean of 4.5 years. During the follow-up period, repeat angioplasty of the original stenosis was performed in 3 patients and another patient underwent dilatation of a new lesion which developed in the aorta. According to clinical and noninvasive studies, these 4 patients, as well as the other 20, have maintained patency of the treated lesions and are symptom free. No immediate complications requiring surgery occurred. We conclude that angioplasty is the initial treatment of choice in focal lesions of the distal abdominal aorta and its bifurcation. PMID- 8435835 TI - The mechanical properties of guidewires. Part I: Stiffness and torsional strength. AB - The stiffness of guidewires varies in accordance with the fourth power of the core diameter. Titanium wires with the same core diameters have one-quarter the stiffness of steel wires. The torsional strength shows the same correlation with the 4th power of the diameter of the core in solid wires. With a few exceptions, spring wires do not have a usable torsional strength. The differences in the stiffness of the wire tips, and the different kinds of transition to the stiff shaft can be explained by differences in the construction of the wires and their tips. PMID- 8435836 TI - The mechanical properties of guidewires. Part II: Kinking resistance. AB - The tolerated acute angle in kinking constitutes a good relative measure for kinking resistance. It is quite a constant parameter for steel wires (about 30 degrees) and for titanium wires (about 80 degrees). The force required to bend a wire to a specific angle depends only on the stiffness of the wire. This means that kinking resistance is also a function of stiffness. PMID- 8435837 TI - Multiple intrahepatic portosystemic venous shunts: treatment by portal vein embolization. AB - A rare case of symptomatic, multiple, intrahepatic, portosystemic venous shunts which was treated by portal vein embolization after surgical cannulation is reported. The patient, having suffered from hepatic encephalopathy, improved dramatically after embolization. This method might be the only choice of therapy for intrahepatic portosystemic shunts of this kind. PMID- 8435838 TI - Thermal laser-assisted angioplasty of renal artery stenosis for renovascular hypertension. AB - Percutaneous transluminal laser-assisted angioplasty of a renal artery stenosis was performed in a 16-year-old woman with renovascular hypertension. The stenotic portion of the renal artery was predilated by delivering Nd-YAG laser energy to the terminal tip of a laser catheter. Although the luminal diameter did not increase sufficiently with laser angioplasty alone, it allowed passage of the balloon catheter and subsequent successful balloon angioplasty. Immediately after dilatation, the patient's blood pressure fell to normal, and plasma renin activity decreased. There were no serious complications. Thermal laser angioplasty seems to be an effective adjunct technique for the treatment of severe renal artery stenosis which does not allow initial passage of a balloon catheter. PMID- 8435839 TI - Posttraumatic bilhemia: conservative management by percutaneous drainage. AB - Posttraumatic bilhemia complicating liver trauma has been managed surgically so far. A case report of a biliary-venous fistula resulting from blunt hepatic trauma managed successfully by percutaneous drainage is presented. A catheter was placed in the right hepatic lobe for reducing intrahepatic pressure. This procedure was followed by a dramatic decrease of bilirubin blood level. This management emphasizes the role of interventional radiology in the treatment of complicated blunt hepatic trauma. PMID- 8435840 TI - New "mesh basket" for percutaneous removal of wall-adherent thrombi in dialysis shunts. AB - A new basket, developed for percutaneous removal of wall-adherent thrombi, was tested in model thrombosed hemodialysis shunts and clinically in two polytetrafluoroethylene grafts and one Brescia-Cimino shunt after recanalization by aspiration thrombectomy. The residual wall-adherent thrombus was removed by one or two passes with the mesh basket. The occlusion material was firmly captured within the mesh and was removed through an 8F sheath without hardly any material being sheared off from the basket. The device adapts well even to tortuous vessel segments and exerts a gentle brush effect. It may prove to be a valuable adjunct to aspiration thrombectomy or to balloon catheter embolectomy. PMID- 8435841 TI - Reading, readability, and patient education materials. PMID- 8435842 TI - [Probability in medicine]. AB - The term "probability", apparently vague, is defined as the ratio of favourable and all cases, e. g. 1/4. Sometimes is expressed as "odds", in the above example 1:3. Mathematical (a priori) probability is calculated according to the following consideration: during accidental tossing of an intact coin the probability of head is 1/2. Statistical (a posteriori) probability is assessed experimentally. If randomization is not respected, the result is doubtful. We call it bias. Probabilities are multiplied (added) if one and (or) another phenomenon should occur. Phenomena which occur or do not occur are frequently governed by binomial division. According to the law of large numbers the a posteriori probability will become the closer to the a priori probability, the larger the number of experiments. Forecasts based on probability are made possible by interferential statistics. In this respect they differ from mere statistical description. Thus optimal decision is achieved under conditions of uncertainty, typical for medicine. This applies to diagnosis as well as treatment. In this way a cut-off value can be selected for a given diagnostic test to achieve an optimal combination of the resulting sensitivity and specificity and the probability of disease (health) in case of a positive (negative) finding can be expressed. The results of statistical testing (e. g. the effectiveness of treatment) is as a rule presented by means of the probability value p, as compared with error alpha which should be assessed in advance. It is, however, necessary to respect also an alternative hypothesis. The latter is unfortunately formulated only rarely. PMID- 8435843 TI - [Mechanisms of the effect of antiviral agents]. AB - This article reviews diverse strategies of rational development of antivirals based upon an interference with processes involved in viral multiplication cycle. With the aid of approved antiviral drugs as well as of antiviral drugs candidates in diverse stages of development this review demonstrates broad variability of chemical structure and mechanism of action in the field of antiviral development. PMID- 8435844 TI - [Perspective and present possibilities of chemotherapy in viral respiratory infections]. AB - The author presents a brief history and contemporary trend of research and trends of antiviral chemotherapy with special attention to possible prophylaxis and treatment of viral respiratory infections. For substances which are at present available the author describes the mechanism of action, mode of administration, pharmacokinetics and undesirable side-effects. PMID- 8435845 TI - [Clinical and pharmacologic review of antiviral agents]. AB - The author presents a review if pharmacokinetics, undesirable effects, drug interactions, dosage, indications and drug forms of antiviral chemotherapeutic agents used for systemic treatment: amantadine and rimantadine (influenza virus A), acyclovir (HSV-1, HSV-2 and VZV), ganciclovir (CMV), zidovudine (HIV), ribavirine (broad spectrum) and fosfocarnet (herpes viruses and HIV), mentioning also vidarabine. All mentioned preparations are at least in some countries commercially available. The author does not mention virostatic agents used only locally and preparations which are at present in the stage of clinical tests. PMID- 8435846 TI - [Strategy of viral replication]. AB - Virus replication is a multistep process which is realized mostly by virus-coded enzymes and in a small part by cell-coded enzymes. Affection of the virus-coded enzymes can be, and is, utilized to restrict virus replication without damaging the host cell. The article provides basic information on the most important steps of viral replication and processes which can be affected in the course of antiviral therapy. PMID- 8435847 TI - Saccharomyces cerevisiae phosphoglucose isomerase and fructose bisphosphate aldolase can be replaced functionally by the corresponding enzymes of Escherichia coli and Drosophila melanogaster. AB - Two glycolytic enzymes, phosphoglucose isomerase and fructose-1,6-bisphosphate aldolase, of Saccharomyces cerevisiae could be replaced by their heterologous counterparts from Escherichia coli and Drosophila melanogaster. Both heterologous enzymes, which show respectively little and no sequence homology to the corresponding yeast enzymes, fully restored wild-type properties when their genes were expressed in yeast deletion mutants. This result does not support notions of an obligatory formation of glycolytic multi-enzyme aggregates in yeast; nor does it support possible regulatory functions of yeast phosphoglucose isomerase. PMID- 8435848 TI - Identification of three genes required for the glucose-dependent transcription of the yeast transcriptional activator ADR1. AB - Glucose repression of the ADH2 gene from Saccharomyces cerevisiae is mediated by the synthesis and activity of the transcriptional activator ADR1. In this study, we isolated mutations in three new genes (SAF1, SAF2 and SAF3) that suppressed the glucose-insensitive expression of ADH2 caused by the ADR1-5c allele. The mechanism by which the SAF genes maintain ADR1-5c function was investigated. Each of the mutated SAF genes was found to suppress ADR1-5c activity by lowering ADR1 5c steady state mRNA levels 5- to 8-fold under glucose growth conditions. ADR1 mRNA levels were similarly affected by the saf mutations. In contrast, mutations in the SAF genes had little or no effect on ADR1-5c or ADR1 mRNA levels under ethanol growth conditions. The stability of ADR1-5c mRNA was unaffected by mutations in each of the SAF genes, implying that the SAF genes are required for the transcription of ADR1 mRNA under glucose growth conditions. The possible function of the three SAF genes in ADR1 expression is discussed. PMID- 8435849 TI - Cloning of the C-URA3 gene and construction of a triple auxotroph (his5, ade1, ura3) as a useful host for the genetic engineering of Candida maltosa. AB - The C-URA3 gene of the n-alkane assimilating-yeast Candida maltosa was cloned by complementation of the ura3 mutation of Saccharomyces cerevisiae. The nucleotide sequence of C-URA3 and its deduced amino-acid sequence showed significant homology to those of the orotidine 5'-phosphate decarboxylases of other fungal species. To construct a useful host for genetic engineering of C. maltosa using C URA3 as a marker, one allele of C-URA3 in a double auxotroph (his5, ade1) was disrupted by C-ADE1, and subsequently two kinds of ura3 mutants were isolated by selecting for spontaneous 5-fluoro-orotic acid (5FOA) resistance. One of the mutants was homozygous for the disruption (ura3::C-ADE1/ura3::C-ADE1); the other was heterozygous (ura3::C-ADE1/ura3). The ura3::C-ADE1 allele in the latter strain was re-substituted by C-URA3 to rescue the adenine auxotroph (his5, ade1, C-URA3/ura3). Finally, by selecting a 5FOA-resistant mutant, a triple auxotroph (his5, ade1, ura3/ura3) was isolated. PMID- 8435850 TI - Isolation of a dsRNA virus from Dipodascus (Endomyces) magnusii. AB - Virus-like particles (VLPs) of 40 nm diameter were isolated from the yeast-like fungus Dipodascus magnusii. These VLPs copurify with several linear double stranded RNA molecules of different size. We have found some polymorphism in both the length and the number of these dsRNAs among six D. magnusii strains. Analysis of CsCl gradient-purified VLPs on PAGE/SDS electrophoresis showed one major protein component with an apparent molecular weight of 75 kDa. PMID- 8435851 TI - Mitochondrial activity is required for the expression of IME1, a regulator of meiosis in yeast. AB - Sporulation in the yeast Saccharomyces cerevisiae occurs in diploid cells following starvation for glucose and nitrogen sources. A key gene in the regulation of the meiotic process is IME1. A well-documented fact is that respiration is necessary for sporulation. We now show that respiration is necessary for the expression of IME1. We suggest that glucose repression of meiosis is transduced through its effect on respiration, in a pathway separate from that of adenylyl cyclase. PMID- 8435852 TI - Further characterization of a large inverted repeat in the mitochondrial genomes of Agaricus bisporus (= A. brunnescens) and related species. AB - The mitochondrial (mt) genome of Agaricus bisporus Ag50 (a heterokaryon) is a 136 kilobase (kb) circular molecule which contains a pair of large inverted repeats (IRs). Two large BAMHI fragments (B1 and B2) which contain the IR regions were further mapped. The repeated regions were determined to be approximately 7.7 kb in length. The mt small ribosomal RNA (S rRNA) gene is located adjacent to one of the repeated regions. Orientational isomers, generated by homologous recombination between the repeated regions, were not observed in mtDNA extractions from Ag50 mycelium (liquid culture) or from Ag50 fruit bodies. We also did not observe any orientational isomers in Ag50HA or Ag50HB, two homokaryons somatically isolated from Ag50. DNA homologous to the Ag50 mt repeated regions was observed in ten other isolates of Agaricus including four isolates of A. bisporus, two isolates of A. subperonatus, two isolates of A. subfloccosus, one isolate of A. bitorquis, and one isolate of A. pattersonae. The repeated regions and the small unique regions in two other heterokaryotic strains of A. bisporus, Ag2 and Ag85, were physically mapped. The repeated regions in these two strains are also in the inverted forms. Restriction endonuclease mapping indicated that the two copies of the IR in Ag85 were not identical. PMID- 8435854 TI - Organization of a 117-kb circular mitochondrial chromosome in IR36 rice. AB - The organization of the mitochondrial genome in the IR36 indica variety of rice was analyzed using constant-field and CHEF gel electrophoresis. The minimum complexity of the genome is estimated to be 300 kb. There was no evidence for a master circular molecule of this size. The genome exists in vivo in multiple subgenomic circular molecules or mitochondrial chromosomes. Using several rare cutting restriction enzymes a restriction map was constructed for a 117-kb circular chromosome. Six genetic loci have been placed on this chromosome; cox1 and atp1 have been assigned precise positions while four additional genes (rrn26, cob2, atp6 and rrn18) were mapped to restriction fragments. PMID- 8435853 TI - Complex organization of the soybean mitochondrial genome: recombination repeats and multiple transcripts at the atpA loci. AB - Identification of the soybean mitochondrial atpA open reading frame (atpA ORF) was based on sequence similarity with atpA genes in other plant mitochondria and partial protein sequencing. The atpA reading frame ends with four tandem UGA codons which overlap four tandem AUG codons initiating an unidentified reading frame, orf214. The atpA-orf214 region is found in multiple sequence contexts in soybean mitochondrial DNA (mtDNA), which can be attributed to the presence of two recombination repeats. A 1-kb repeat spans 600 nucleotides (nt) of atpA N terminal coding region and 400 nt of upstream sequence. Its four configurations correspond to two full-length atpA-orf214 genes and two truncated pseudogenes. A 2-kb repeat lies 3 kb downstream from the 1-kb repeat. Restriction maps of cosmid clones suggest that a 10-kb segment containing both repeats is itself duplicated in the mt genome. With two recombination repeats present in a total of three copies per genome, soybean mtDNA is expected to consist of a complex population of subgenomic molecules. Transcription of the atpA loci was analysed by Northern blotting and S1 nuclease protection. The atpA genes express multiple transcripts with one major 3' end and heterogeneous 5' sequences extending several kb upstream of the atpA coding region. The atpA gene and orf214 are co-transcribed on all major transcripts. The pseudogenes do not express stable RNAs. PMID- 8435855 TI - Comparative analysis of a recombining-repeat-sequence family in the mitochondrial genomes of wheat (Triticum aestivum L.) and rye (Secale cereale L.). AB - The mitochondrial genomes of wheat and rye each contain a three-member family of recombining repeat sequences (the "18S/5S repeat") that encode genes for 18S and 5S rRNAs (rrn18 and rrn5) and tRNA(fMet) (trnfM). Here we present, for wheat and rye, the sequence and boundaries of the "common sequence unit" (CSU) that is shared between all three repeat copies in each species. The wheat CSU is 4,429 base-pairs long and contains (in addition to trnfM, rrn18 and rrn5) a putative promoter, three tRNA-like elements ("t-elements"), and part of a pseudogene ("psi atpAc") that is homologous to chloroplast atpA, which encodes the alpha subunit of chloroplast F1 ATPase. The rye CSU is somewhat smaller (2,855 base pairs) but contains much the same genic and other sequence elements as its wheat counterpart, except that two of the three t-elements as well as psi atpAc are found in only one of the three downstream flanks of the 18S/5S repeat, outside the CSU boundaries. In interpreting the sequence data in terms of the evolutionary history of the 18S/5S-repeat family of wheat and rye, we conclude that: (1) the wheat-rye form of the 18S/5S repeat most likely originated between 3 and 14 million years ago, in a lineage that gave rise to wheat and rye but not to barley, oats, rice or maize; (2) the close linkage (1-bp apart) between trnfM and rrn18 is similarly limited in its taxonomic distribution to the wheat/rye lineage; (3) the trnfM-rrn18 pair arose via a single mutation that inserted a sequence block containing trnfM immediately upstream of rrn18; and (4) the presence of a putative promoter upstream of rrn18 in all wheat and rye repeats is consistent with all three repeat copies being transcriptionally active. We discuss these conclusions in the light of the possible functional significance of recombining-repeats in plant mitochondrial genomes. PMID- 8435856 TI - In-frame length mutations associated with short tandem repeats are located in unassigned open reading frames of Oenothera chloroplast DNA. AB - Chloroplast DNAs were compared between two closely related species in the subsection Munzia of the genus Oenothera. A restriction fragment length dimorphism (273 bp) within the large inverted repeats was localized to an unassigned open reading frame that is homologous to ORF 2280 of tobacco chloroplast DNA. This dimorphism is due to different copy numbers of various short tandem repeated sequences, with each repeat unit specifying an in-frame addition or deletion. Other small length mutations were detected within an unassigned reading frame that appears to be homologous to the tobacco ORF 1244, and in the non-coding sequence upstream of that frame. These insertions and/or deletions are all associated with short direct repeats that lie in tandem. PMID- 8435858 TI - Cloning and characterization of a mouse 3-methyladenine/7-methyl-guanine/3 methylguanine DNA glycosylase cDNA whose gene maps to chromosome 11. AB - In Escherichia coli, the repair of 3-methyladenine (3MeA) DNA lesions by DNA glycosylases prevents alkylation induced cell death. We described previously the isolation of a human 3MeA DNA glycosylase (AAG) cDNA that maps to chromosome 16 and hybridizes to specific genomic DNA fragments from a number of mammals, including mouse. As a first step in the generation of a 3MeA DNA glycosylase deficient mouse by homologous replacement in embryonic stem cells, we have cloned the mouse 3MeA DNA glycosylase cDNA. The cloned 1095 base pair cDNA contains a complete 333 amino acid open reading frame that predicts a 36.5 kDa protein and hybridizes to a 1.5 kb mRNA transcript. Mouse 3MeA DNA glycosylase (Aag) transcript levels vary by up to 21 fold among tissues, being highest in the testes and lowest in the heart. The Aag cDNA encodes a glycosylase able to release 3MeA, 7-methylguanine (7MeG) and 3-methylguanine (3MeG) from alkylated DNA. The expression of Aag in E. coli provides substantial resistance against killing by methylating agents, but, unlike its E. coli counterparts, the Aag glycosylase fails to protect against killing by ethylating and propylating agents. A 232 amino acid stretch of the predicted mouse protein shares extensive amino acid identity with rat (93%) and human (83%) 3MeA DNA glycosylases and we observe that all three mammalian glycosylases have a bipartite nuclear localization signal. The Aag gene maps to mouse chromosome 11, suggesting a segment of conserved synteny between mouse chromosome 11 and human chromosome 16, which bears the human 3MeA DNA glycosylase gene. Cloning the mouse 3MeA DNA glycosylase cDNA is a step toward understanding the role of this DNA repair enzyme in mammals. PMID- 8435857 TI - A novel Euglena gracilis chloroplast operon encoding four ATP synthase subunits and two ribosomal proteins contains 17 introns. AB - The structure of a Euglena gracilis chloroplast operon encoding four subunits of the chloroplast ATP synthase complex and two ribosomal proteins has been determined. These six genes contain 17 introns. This operon is transcribed as a hexacistronic primary transcript which is subsequently processed to monocistronic mRNAs. The linear order of these genes, 5'-rps2-atpI-atpH-atpF-atpA-rps18-3' , encoding ribosomal protein S2, chloroplast ATP synthase subunits CF0IV, CF0III, CF0I, CF1 alpha and ribosomal protein S18, respectively, is similar to the equivalent operons of prokaryotes, cyanelles and land-plant chloroplasts. This operon differs from those of these other organisms in the co-transcription of rps18 and in intron content. PMID- 8435859 TI - Molecular dosimetry of the food-borne carcinogen MeIQx using adducts of serum albumin. AB - Incubation of mouse serum albumin with the food borne carcinogen [2-14C]-Amino 3,8,-dimethylimidazo[4,5-f]quinoxaline (14C-MeIQx) in the presence of mouse hepatic microsomes and an NADPH-regenerating system in vitro resulted in the formation of adducts of MeIQx with albumin, which increased proportionately with time for at least 120 min (approximately 1 pmol equivalents/mg of protein/min). We have previously shown in male Swiss Webster mice in vivo that 14C-MeIQx bound covalently to serum proteins and that the formation of adducts was dose dependent. 14C-MeIQx (100 mg/kg, i.p.) was administered to male (MF1) mice which were killed 24 h later. Serum albumin was purified by affinity chromatography and covalent binding of 14C-MeIQx was assessed. Total covalent binding of MeIQx to albumin was 14.0 +/- 5.2 pmol per mg albumin, which was 5-fold greater than to haemoglobin. Following mild acid hydrolysis, 1.25 pmol MeIQx per mg albumin was liberated as free amine, as determined by gas chromatography negative ion mass spectrometry (GC-MS). This represents 9% of total MeIQx adducted to albumin in vivo (cf 1.3% adducted to haemoglobin). These results suggested that adducts of MeIQx with serum albumin should provide a significantly more sensitive dosimeter than those with haemoglobin. We therefore investigated this approach with serum protein samples from three volunteers. Human serum albumin and non-serum albumin protein fractions were separated by affinity chromatography, before being subjected to GC-MS analysis for hydrolysable adducts of MeIQx. The levels of MeIQx in control samples, and from the release of the putative sulphinamide adducts in hydrolysed samples were below the limits of detection of the GC-MS assay (29 +/- 2.6 amol MeIQx/mg albumin). Despite an increase of 2 orders of magnitude in sensitivity, compared with haemoglobin, it is unlikely that the sulphinamide adduct of MeIQx with human serum albumin can be used as a dosimeter for human aminoimidazoazaarene exposure. PMID- 8435860 TI - Synthesis of the prototype DNA-protein cross-link, 1-(guan-1-yl)-2-(cysteine-S yl)ethane, and its role in the reactions of the haloethylnitrosoureas. AB - The haloethylnitrosoureas form a cytotoxic DNA cross-link in a series of reactions which involves initial alkylation of the O6 position of guanine and rearrangement to the intermediate, 1,O6-ethanoguanine; 1,O6-ethanoguanine then reacts with a neighboring cytosine base. O6-Alkylguanine-DNA alkyltransferase can interrupt this process after the initial alkylation step by removing the alkyl group from the O6 position of guanine. Recent evidence suggests that the O6 alkylguanine-DNA alkyltransferase also recognizes 1,O6-ethanoguanine as a substrate, becoming bound to DNA when it interacts with that intermediate. It has also been shown that glutathione becomes bound to haloethylnitrosourea-treated DNA, apparently through chemical interaction with 1,O6-ethanoguanine. Since both of these reactions involve the thiol group of cysteine, we have examined the reaction of cysteine with 1,O6-ethanoguanine, characterizing the prototype DNA protein cross-link, 1-(3-cytosinyl),2-(1-guanyl)ethane, which is formed in this reaction. These results establish a competitive reaction with 1,O6-ethanoguanine as a likely route to protein-DNA cross-linking. PMID- 8435861 TI - Immunoaffinity purification and gas chromatography-mass spectrometric quantification of 3-alkyladenines in urine: metabolism studies and basal excretion levels in man. AB - Immunoaffinity gels were prepared by coupling monoclonal antibody (Mab) EM-6-47 to protein A-Sepharose, and were used to make small columns retaining 3 alkyladenines (3-alkAde) of diverse structure. An analytical procedure for determination of 3-methyladenine (3-MeAde), 3-ethyladenine (3-EtAde), 3-(2 hydroxyethyl)adenine (3-HOEtAde) and 3-benzyladenine (3-BzAde) was developed. Deuterated internal standards (d3-3-MeAde, d5-3-EtAde, d4-3-HOEtAde and d7-3 BzAde) were synthesized and added to urine samples prior to immunoaffinity purification. 3-alkAde were separated and quantitated as tert-butyl-dimethylsilyl (TBDMS) derivatives by capillary gas chromatography-low resolution mass spectrometry (GC-MS). Detection limits for 3-MeAde, 3-EtAde and 3-HOEtAde were 0.2 pmol/ml urine and for 3-BzAde, 1 pmol/ml urine. Studies in two volunteers showed that 3-MeAde and 3-HOEtAde were excreted almost quantitatively (> 90%) within 24 h, that 3-EtAde was less well excreted (67-74%) and that 3-BzAde was poorly excreted (21-25%). Studies on basal levels of 3-alkAde urinary excretion in three volunteers showed that 3-MeAde was > 90% derived from the diet as the preformed product. 3-HOEtAde was present at approximately 10 nmol/day and was reduced to approximately 1 nmol/day when the diet was standardized suggesting that it is also dietary in origin. 3-BzAde was not detected in human urine. 3 EtAde was not only excreted at low levels (< 1 nmol/day) but was also only very slightly affected by diet. This general and sensitive method will be useful in biomonitoring studies in subjects exposed to alkylating agents of diverse structure. PMID- 8435862 TI - Inhibition of tumor formation from grafted murine papilloma cells by treatment of grafts with staurosporine, an inducer of squamous differentiation. AB - The microbial alkaloid staurosporine induces responses associated with protein kinase C activation, resulting in terminal differentiation in cultures of both normal and neoplastic mouse epidermal cells. As a cancer chemotherapy model, we treated grafts of mouse epidermal tumor cell lines 308 and SP-1 repeatedly with staurosporine. A dose-dependent inhibition of tumor formation, maximal at 0.025 nmol per treatment, was observed. Higher and lower doses were less effective, suggesting a specific target for staurosporine action. A single, low-dose treatment 2 weeks after grafting also markedly reduced tumor formation. Although in vitro evidence suggests that staurosporine-induced terminal squamous differentiation results from activation of protein kinase C, we found no inhibition of tumor growth in similar studies with the protein kinase C activator 12-O-tetradecanoylphorbol-13-acetate. These results indicate that staurosporine is an effective antitumor agent for eradicating squamous cell tumors in vivo. PMID- 8435863 TI - DNA single- and double-strand breaks produced by ferric nitrilotriacetate in relation to renal tubular carcinogenesis. AB - Fe(III) bound to a chelator, nitrilotriacetate (NTA), has been reported to induce a high frequency of adenocarcinoma localized to the proximal tubules of the kidney in rodents. In order to examine possible mechanisms for the carcinogenic activity, we investigated the in vitro production of single- and double-strand breaks in DNA mediated by iron alone or Fe-NTA chelate using supercoiled plasmid pZ189. Neither Fe(III) nor NTA alone broke DNA. Fe(III) plus NTA together mediated the efficient oxidative production of DNA single- and double-strand breaks in the presence of reducing agents (ascorbate >> H2O2 > cysteine). The Fe(III):NTA ratio (1:4) that was found to be optimal for DNA strand breakage was similar to the ratio that produced adenocarcinomas in rodents. Maximal Fe-NTA mediated DNA damage in vitro was induced under conditions of neutral pH, low ionic strength, presence of reducing agent and absence of albumin. These conditions are present exclusively in the cortical proximal tubules of the kidney, the only location where toxicity and carcinogenicity of Fe-NTA has been observed. Thus, localized DNA damage may explain the anatomic site preferred by Fe-NTA-induced carcinogenesis. PMID- 8435864 TI - Metabolism of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3 pyridyl)-1-butanone in the patas monkey: pharmacokinetics and characterization of glucuronide metabolites. AB - The metabolism of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3 pyridyl)-1-butanone (NNK) was examined in the patas monkey, in order to provide further information about NNK metabolic pathways in primates. Female patas monkeys were given i.v. injections of [5-3H]NNK, and metabolites in serum and urine were analyzed by HPLC. Metabolism by alpha-hydroxylation of NNK was rapid and extensive, and the products of this pathway, 4-hydroxy-4-(3-pyridyl)butyric acid and 4-oxo-4-(3-pyridyl) butyric acid, accounted for a relatively large proportion of serum and urinary metabolites at all time points. This is significant because the formation of these products is associated with modification of DNA by NNK. The other major metabolic pathway was carbonyl reduction to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), which detected both unconjugated and diastereomeric O-glucuronides. One of these glucuronides had been previously identified in rat urine, but the other diastereomer, which was the more prevalent of the two in serum and urine, had not been observed in studies of NNK metabolism in rodents. It was characterized by its spectral properties, by enzymatic hydrolysis to NNAL, and by derivatization of the released NNAL enantiomer with (R)-(+)-alpha-methylbenzylisocyanate. The two NNAL glucuronides accounted for 15-20% of the urinary metabolites in monkeys given 0.1 micrograms/kg NNK, which is similar to a smoker's dose, suggesting their use as dosimeters of NNK exposure in humans. Pharmacokinetic parameters were consistent with those observed in previous studies of nitrosamines, and varied predictably with body weight of five species. The results of this study have provided new insights relevant to assessing human metabolism of NNK. PMID- 8435865 TI - Studies on guanine adducts excreted in rat urine after benzene exposure. AB - Investigations with [14C]benzene indicate the formation of base adducts in vivo. Experiments to separate adducts from urine of [14C]benzene-exposed rats suggest the excretion of eight labeled compounds different from benzene metabolites. In order to obtain information about their structure we synthesized N7-, O6-, C8- and N2-phenylguanine. With regard to their chromatographic properties we compared these phenylguanines with products obtained by alkylation of guanine by metabolites of unlabeled and 14C-labeled benzene in vivo with HPLC with UV detection and liquid scintillation counting. Furthermore GC/MS and ELISA techniques were used to detect N7-phenylguanine. Phenylguanines could not be identified in collected DNA fractions. The labeled compounds detected in urine of [14C]benzene-exposed rats also showed deviations from the HPLC elution patterns of our reference substances. Even N7-phenylguanine, formerly suspected to be a urinary metabolite of benzene in the rat, could not be detected with these refined HPLC methods. With GC/MS a compound was found in trace amounts in concentrated rat urine samples, which had a similar fragmentation pattern to N7 phenylguanine. These data could not be confirmed by a sensitive immunological assay (ELISA). No N7-phenylguanine was detected in purified rat urine samples. The results suggest the excretion of a hydroxylated phenylguanine which may be formed in liver or bone marrow DNA by highly reactive hydroxylated intermediates. The OH group might be lost because of the high temperatures during GC/MS measurements. A hydroxy group at the phenyl-ring of N7-phenylguanine will cause other elution properties in HPLC compared to N7-phenylguanine. PMID- 8435866 TI - Intercellular communication in colonies of Syrian hamster embryo cells and the susceptibility for morphological transformation. AB - The levels of gap junctional intercellular communication (GJIC) were studied in normal, morphologically altered and morphologically transformed colonies formed in the Syrian hamster embryo (SHE) cell transformation assay. The colonies were selected from non-exposed dishes or dishes exposed to 12-O-tetradecanoylphorbol 13-acetate (TPA, 0.16 microM), di(2-ethylhexyl)phthalate (DEHP, 77 microM), Na orthovanadate (vanadate, 3.4 microM) or dieldrin (25 microM) for 7 days during colony formation. TPA, DEHP and vanadate induced increased frequencies of morphological transformation of colonies. At the same time, TPA and DEHP decreased GJIC in the colonies by approximately 30% under the conditions used. All categories of colonies were equally affected. Vanadate did not change the level of GJIC in any of the categories of colonies compared to unexposed control. Dieldrin strongly suppressed GJIC in all colonies without increasing the frequency of transformation. The compounds affected GJIC after short-term exposures (4 and 24 h) to cell monolayers rather similarly to that found after long-term exposure to the colonies. Transformation assays with coexposure of dieldrin together with the transforming agents vanadate, DEHP or benzo[a]pyrene did not increase transformation frequencies compared to the transforming agents alone. The GJIC level in all coexposure groups was similar to that of dieldrin alone. Furthermore, regardless of whether dieldrin was present or not, removal of vanadate 24 h before fixation of the colonies caused a slight decrease in the transformation frequency. The results suggest that: (i) morphologically transformed colonies have the same ability of intercellular communication as normal colonies; (ii) decreased GJIC is probably not either sufficient or necessary to induce transformation of SHE cell colonies; (iii) a decreased level of GJIC does not necessarily increase the susceptibility of SHE cells for transformation; and (iv) inhibition of GJIC may not have an impact on the maintenance of the transformed phenotype of SHE cell colonies. PMID- 8435867 TI - Enhancing effect of concomitant L-ascorbic acid administration on BHA-induced forestomach carcinogenesis in rats. AB - The effects of the synthetic antioxidant butylated hydroxyanisole (BHA) and naturally occurring antioxidants such as L-ascorbic acid (AsA; vitamin C), citric acid, benzoic acid or gallic acid in combination, on the development of rat forestomach epithelial lesions were investigated. A dietary level of 2.0% was selected for all antioxidants and the experimental period was 1 year. As compared with BHA alone, treatment with AsA in combination with BHA increased the severity of the hyperplasia in the mid-region, but not in the prefundic region of the forestomach epithelium, as well as the multiplicity of forestomach tumors. Furthermore, incidences of squamous cell carcinomas (SCCs) in the forestomach were significantly elevated in this group, while papilloma development only showed a tendency to increase. In addition, SCC invasion into the muscle layer of the forestomach was observed only in the BHA + AsA group. Treatment with the other antioxidants did not affect BHA-induced forestomach lesion development. The present study demonstrated that AsA can clearly enhance BHA forestomach carcinogenesis. PMID- 8435868 TI - Modifying effects of benzyl isothiocyanate and benzyl thiocyanate on DNA synthesis in primary cultures of rat hepatocytes. AB - The effects of benzyl isothiocyanate (BITC) and benzyl thiocyanate (BTC) on two types of DNA synthesis were examined in hepatocyte primary cultures (HPC). Male F344 rats were fed BITC- or BTC-containing diets at a concentration of 400 p.p.m. Using hepatocytes isolated from these rats, DNA repair was measured by unscheduled DNA synthesis (UDS) for some genotoxic carcinogens, e.g. 2 acetylaminofluorene (AAF), methylazoxymethanol (MAM) acetate, 9,10-dimethyl-1,2 benzanthracene (DMBA) and diethylnitrosamine (DEN), and compared with that in the hepatocytes from rats without BITC or BTC treatment. Replicative DNA synthesis (RDS) was also evaluated in the hepatocytes of rats with or without thiocyanate treatment. Both BITC and BTC reduced UDS elicited by these carcinogens. The level of RDS in the hepatocytes of rats exposed to BITC or BTC was markedly lower than in the cells of rats without BITC or BTC exposure. These results indicate that in vivo exposure to BITC and BTC suppressed carcinogen-induced genotoxicity and cell proliferative activity and suggest that this assay may prove useful in detecting chemopreventive agents for cancer and in investigating the properties of carcinogenesis modifiers. PMID- 8435869 TI - High gastric juice ascorbic acid concentrations in members of a gastric cancer family. AB - Gastric juice ascorbic acid, total vitamin C, nitrite and N-nitroso-compound concentrations were determined in fasting gastric juice from four second generation members of a gastric cancer family, all of whom had Helicobacter pylori-associated chronic gastritis and intestinal metaplasia. Juice pH, nitrite and N-nitroso-compound concentrations were low. Juice ascorbate levels were comparable to those found in subjects with normal histology. The findings are contrary to our previous experience with juice ascorbate in H. pylori gastritis. PMID- 8435870 TI - Inhibitory effect of curcumin on 12-O-tetradecanoylphorbol-13-acetate-induced increase in ornithine decarboxylase mRNA in mouse epidermis. AB - Application of 5 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) to the skin of female CD-1 mice led to a rapid increase in the concentration of epidermal ornithine decarboxylase (ODC) mRNA from an undetectable level in control mice to a high maximum level at 4-5 h after TPA administration. The concentration of epidermal ODC mRNA then decreased rapidly during the next 5 h. The time course for TPA-induced increases in epidermal ODC enzyme activity paralleled very closely the time course for TPA-induced increases in ODC mRNA. Topical administration of 1, 3 or 10 mumol curcumin together with 5 nmol TPA inhibited by 66, 81 and 91% respectively TPA-induced increases in epidermal ODC enzyme activity measured 5 h later. In a parallel study, TPA-induced increases in the concentration of epidermal ODC mRNA was inhibited by 54, 85 and 82% respectively. Intraperitoneal injection of 10 or 30 mumol curcumin 1h before topical application of 5 nmol TPA inhibited TPA-induced increases in epidermal ODC enzyme activity by 75 or 89% respectively. In a parallel study, the induction of epidermal ODC mRNA was inhibited by 53 and 65% respectively. The results indicate that curcumin inhibits TPA-induced increases in epidermal ODC enzyme activity by inhibiting the synthesis and/or enhancing the breakdown of ODC mRNA. PMID- 8435871 TI - A method for selection of forward mutations in supF gene carried by shuttle vector plasmids. AB - The supF gene of Escherichia coli has been widely used as a mutagenic target in several shuttle-vector plasmids. Mutations in this gene are usually screened by a colony colour assay based on the suppression of a lacZ amber mutation in an appropriate bacterial indicator strain. This screening method cannot measure the low mutation frequencies usually detected in prokaryotes, and therefore precludes the use of supF gene for studying mutational spectra in bacteria. In this paper we report the development of a simple method for the selection of supF forward mutations in shuttle-vector plasmids. The method has implied the construction of an araD- araC(Am) mutant strain (MBL50) of E.coli. The L-arabinose sensitivity caused by the accumulation of a toxic intermediate in araD- mutants is abolished in MBL50 because the araC(Am) mutation blocks the L-arabinose catabolic pathway. Strain MBL50 becomes sensitive to L-arabinose when transformed with a supF+ plasmid but remains resistant upon transformation with a supF- mutant. This new L arabinose resistance selection method was able to detect supF- mutant fractions up to three orders of magnitude below those determined with the colony colour screening assay. The method was further validated by carrying out in vivo mutagenesis experiments with N-methyl-N-nitrosourea (MNU) and a shuttle-vector bearing strain (UC2109) completely defective in O6-methylguanine (O6meG) alkyltransferase repair capacity. The DNA sequence alterations of 22 independent supF- mutants induced by MNU were determined. All mutations were G:C-->A:T transitions in agreement with the predicted significance of the mispairing potential of the O6meG lesion. A preference for the sequence 5'-GG-3' was detected, revealing a 5'-flanking base influence. The accumulation of all 22 MNU induced mutations in three sites of the supF genes might be related to the lack of O6meG alkyltransferase repair capacity of strain UC2109. The L-arabinose resistance method described in this paper allows rapid scoring and sequencing of forward mutations in the supF gene on shuttle-vectors, thus permitting its use as a genetic target for repair and mutagenesis studies in bacteria. Since shuttle vectors replicate both in bacteria and mammalian cells, this method makes it possible to compare prokaryotic and eukaryotic mutational spectra. PMID- 8435872 TI - Determination of polycyclic aromatic hydrocarbons in urine from coke-oven workers with a radioimmunoassay. AB - Considerable amounts of polycyclic aromatic hydrocarbons (PAH) are present in the workplace. In order to obtain a better understanding of the occupational hazards connected with PAH exposure various biomonitoring methods need to be applied. The level of PAH in urine collected from coke-oven workers has been measured by a recently developed radioimmunoassay. A significant correlation between estimated exposure levels for PAH and urinary levels of PAH was observed. During the winter period the control group was found to have an average concentration of 0.44 ng PAH/mmol creatinine, whereas the low, medium and high exposure groups contained 0.44, 0.71 and 0.85 ng PAH/mmol creatinine respectively. The urinary PAH level in the samples collected during the summer period was higher, i.e. 0.81, 0.94 and 1.10 ng PAH/mmol creatinine, for the low, medium and high exposure groups. Furthermore, a correlation was also observed between smoking and levels of urinary PAH. We conclude that this radioimmunoassay may be suitable as a simple and sensitive routine assay for monitoring individuals exposed to PAH. PMID- 8435873 TI - Enhancement of binding rate of RecA protein to DNA by carcinogenic benzo[a]pyrene derivatives and selective change of adduct conformation. AB - The association kinetics of RecA protein from Escherichia coli to DNA is strongly enhanced if even a minor fraction of DNA bases has been modified by a carcinogenic (+)-anti metabolite of benzo[a]pyrene (BPDE). The enhancement is much smaller with the less carcinogenic (-)-anti enantiomer of BPDE suggesting the possibility that the RecA protein binds selectively to the proto-oncogenic target. Most importantly, the binding of RecA to DNA modified with the latter enantiomer is found to give rise to a reorganization of this BPDE adduct from an intercalation site into a minor groove site. This indicates that the binding mechanism of RecA is via intercalation of some amino acid moiety, a discovery that could explain the approximately 50% contour length increase of the DNA within its fibrous complex with RecA. PMID- 8435874 TI - The triphenylethylene drug tamoxifen is a strong liver carcinogen in the rat. AB - Tamoxifen (TAM) is used in the treatment of breast cancer and is being given to healthy women to inhibit breast cancer. The present study examines the effects of TAM in female rats exposed for up to one year. Starting at 6 weeks of age, groups of 55-57 female Sprague-Dawley rats were given TAM by gavage daily at 2.8, 11.3 or 45.2 mg/kd body weight/day, for up to 1 year with two recovery segments, 4 weeks of recovery after 6 months of exposure, and 3 months of recovery after 12 months of exposure. Complete necropsies and histopathology were performed. Drug related mortality was highest in the high TAM group. In the two high dose groups, hepatoproliferative lesions were present in time- and dose-related incidence, severity and multiplicity. In the high dose rats, at 6 months, hepatocellular adenomas and carcinomas were observed in 71 and 29% of rats respectively. With 1 month of recovery, at 7 months the adenomas and carcinomas were increased to 75%. At 12 months the adenomas were present in 50% and carcinomas in 75% of high dose rats. In the mid dose group, liver lesions were not found until 12 months; at this time 50% had adenomas and 10%, carcinomas. After a 3 month recovery period, 45% exhibited adenomas and 45%, carcinomas. Thus, TAM at 45.2 mg/kg/day elicited hepatocellular neoplasia sometime between 3 and 6 months of administration. At 11.3 mg/kg the neoplastic process was evident at 12 months. At 2.8 mg/kg, no hepatoproliferative changes were found. The strong hepatocarcinogenic effect of TAM in rats raises issues bearing on the prophylactic chronic administration to healthy women. PMID- 8435875 TI - C57BL/6 mice are resistant to tumor promotion by full thickness skin wounding. AB - The present study demonstrates that C57BL/6 mice, previously shown to be relatively resistant to skin tumor promotion by phorbol esters as well as several other classes of tumor promoters, are resistant to skin tumor promotion by full thickness skin wounding. Two separate experiments were performed comparing female SENCAR and C57BL/6 mice for their sensitivity to skin tumor promotion by skin wounding following initiation with 7,12-dimethylbenz[a]anthracene (DMBA). In the first experiment, groups of mice were initiated with 25 nmol DMBA and then received full thickness skin wounds in the initiated skin 2 weeks later. Neither SENCAR nor C57BL/6 mice developed skin tumors during the 26 weeks following initial wounding. However, these groups were rewounded in week 27 and 14 weeks later the SENCAR mice had developed a significant tumor response (0.75 papillomas per mouse, 55% incidence). At this time, the C57BL/6 mice still did not have a tumor response significantly different from the acetone-initiated controls. A second experiment was performed using a 100 nmol initiating dose of DMBA. Fifteen weeks after initial wounding in this experiment, the group of SENCAR mice had 0.76 papillomas per mouse (41% incidence) whereas no tumors were present in the group of C57BL/6 mice, even 31 weeks after the initial wounding. The results demonstrate that C57BL/6 mice are resistant to an endogenous skin tumor promotion mechanism and strongly support a link between skin tumor promotion by several classes of chemical promoters and full thickness wounding. PMID- 8435876 TI - Effect of 5-methylcytosine as a neighboring base on methylation of DNA guanine by N-methyl-N-nitrosourea. AB - Effects on N-methyl-N-nitrosourea (MNU) mediated methylation of the N7 position of guanine were compared in defined sequences of DNA containing cytosine or 5 methylcytosine (5mC) using a Maxam-Gilbert sequencing technique. Cytosine methylation in 5'-CpG-3' pairs within a subcloned fragment of the 5' region of the human HPRT gene was generated with SssI methylase and S-adenosylmethionine. Cytosine methylation was demonstrated by both the inhibition of DNA restriction by methylation sensitive endonucleases and the lack of cleavage at 5 methylcytosines by hydrazine. MNU-dependent methylation of the N7 position of guanine was inhibited up to 18% when 5mC was a 5' neighboring base to guanine and was inhibited up to 36% in an alternating CpG region in which both 5' and 3' neighboring bases of guanine were enzymatically altered to 5mC. It can be concluded that 5-methylcytosine has discernible effects on MNU methylation of the N7 position of specific guanine bases in DNA. PMID- 8435877 TI - The relationship between peripheral immunoactive inhibin, human chorionic gonadotrophin, oestradiol and progesterone during human pregnancy. AB - OBJECTIVE: The objective of this study was to investigate serial changes in the plasma concentration of inhibin in both the very early days of pregnancy following implantation and in late pregnancy. The timing of the changes in inhibin concentration relative to changes in the concentrations of other hormones of pregnancy was also investigated. DESIGN: Serial observations of the peripheral concentrations of inhibin and other hormones in two groups of healthy volunteers in (a) early pregnancy and (b) late pregnancy. PATIENTS: (a) Four healthy women recruited on cessation of contraception prior to conception. (b) Nine healthy women recruited at the antenatal clinic. MEASUREMENTS: In the early pregnancy subjects, the concentrations of inhibin, progesterone, oestradiol and hCG were measured in plasma samples obtained three times per week from day 8 to day 10 of each menstrual cycle until 11 weeks after the last menstrual period in the conception cycle. In the late pregnancy subjects, plasma samples were obtained at 4-week intervals from 12 weeks until term. RESULTS: The concentration of inhibin, progesterone and oestradiol in conception cycles were similar to those in the preceding cycles until the mid/to late-luteal phase of the cycle when hCG was first measureable. By day 12 of the luteal phase the concentration of inhibin was significantly higher in the pregnancy cycle than in the non-pregnancy cycle (P < 0.05) and progressively increased after the time of the missed menstrual period. The concentration of inhibin reached a peak (513.0 U/l, CI 442.1-595.3) by day 47 when the concentration of hCG was maximal. In early pregnancy the concentration of inhibin was correlated with that of hCG (r = 0.361; P < 0.01) as well as progesterone (r = 0.584, P < 0.001) and oestradiol (r = 0.602, P < 0.001). After 12 weeks there was no significant correlation between hCG and inhibin although significant correlations persisted with progesterone (r = 0.553, P < 0.001) and oestradiol (r = 0.361, P < 0.01). CONCLUSIONS: The corpus luteum makes a significant contribution to the production of inhibin in early pregnancy while after 12 weeks the placenta is the major source. PMID- 8435878 TI - Pituitary apoplexy and sudden blindness following the administration of gonadotrophin releasing hormone. AB - Pituitary apoplexy has been reported as a rare complication of combined tests and of TRH administration in prolactinomas. A 54-year-old man with a pituitary macroadenoma had a single injection of 100 micrograms GnRH. Twenty minutes later he complained of increasing headache and vomited. These symptoms settled spontaneously and were attributed to the pharmacological effects of GnRH. Five hours later he was found to be blind and disorientated without spontaneous complaint. Emergency CT showed a large adenoma with central necrosis, consistent with pituitary apoplexy. An urgent surgical decompression was carried out and necrotic haemorrhagic debris removed. Baseline bloods revealed non-pulsatile FSH of 40 U/l with LH 0.3 U/l with no hormonal response to GnRH administration, but the sequence of events strongly suggests a causal relationship between this and pituitary apoplexy. To our knowledge this is the first time that GnRH administration has been associated with pituitary apoplexy of a glycoprotein secreting pituitary adenoma. PMID- 8435879 TI - Risk factors for osteoporosis in men. PMID- 8435880 TI - Iodine deficiency and goitre in children in Sudan. PMID- 8435881 TI - Endemic juvenile hypothyroidism in a severe endemic goitre area of Sudan. AB - OBJECTIVE: The aim of the study was to assess thyroid function, iodine intake and exposure to dietary goitrogens of children living in an area with a high prevalence of goitre, in the region of Darfur, Sudan. DESIGN: In a village where goitre affected approximately 85% of children, a cross-sectional survey of thyroid function was performed in children 0-7 years old. PATIENTS: Twenty neonates and 190 children, aged 1 month to 7 years, were included. MEASUREMENTS: Thyroid hormones, urinary iodide and thiocyanate excretion were measured. RESULTS: Mean +/- SD serum T4 was below the normal range at birth (82 +/- 50 nmol/l) and in the age group less than 2 years (73 +/- 46). Children older than 2 years had even lower serum T4: 37 +/- 37 (P < 0.001) at 3-4 years and 36 +/- 38 (P < 0.001) at 5-7 years. Mean serum TSH was 25.8(6.2-107.7) mU/l at birth, 8.3(2.5-27.8) in the group less than 2 years, 15.3(2.9-79.1) at 3-4 years and 16.4(2.7-98.3) at 5-7 years. The overall prevalence of hypothyroidism (TSH > 50 mU/l) was 24%. Mean urinary thiocyanate was high at birth (107 +/- 69 mumol/l), normal in the group less than 2 years and higher in children older than 2 years (126 +/- 69 mumol/l) (P < 0.001). All age groups had a low urinary iodide concentration. CONCLUSION: Hypothyroidism was very frequent in each age group. The higher frequency of hypothyroidism observed in weaned children (> 2 years) was attributed to the combined effects of iodine deficiency and goitrogens (thiocyanate and glycosylflavones) derived from millet. PMID- 8435882 TI - Effect of 131I treatment on the calcitonin response to calcium infusion in hyperthyroid patients. AB - OBJECTIVE: The objective was to evaluate the effect of 131I treatment for hyperthyroidism on calcitonin secretion by thyroid C-cells. DESIGN: Determination of basal calcitonin levels and calcitonin secretory reserve before and after 131I administration. PATIENTS: Seventeen hyperthyroid patients (15 female, two male) were studied before, and 2 months after 131I treatment, and 12 of these patients were restudied 8 months after 131I treatment. MEASUREMENTS: Calcitonin response was assessed by measuring basal and post calcium infusion calcitonin levels. Basal TSH, T3, and T4 levels were also determined at each study. RESULTS: The rise of plasma calcium resulted in statistically significant increase of plasma calcitonin levels before 131I treatment (10.9 +/- 2.4 pmol/l), while this response was significantly diminished 2 and 8 months after treatment (2.6 +/- 0.7 and 1.6 +/- 0.3 pmol/l, respectively). No correlation was found between the calcitonin response and age or plasma TSH. CONCLUSION: Our results demonstrate that 131I treatment for hyperthyroidism may seriously damage thyroid C-cells and cause calcitonin deficiency. PMID- 8435883 TI - Characterization of a novel mutant human thyroid hormone receptor beta in a family with hereditary thyroid hormone resistance. AB - OBJECTIVE: We wished to determine the abnormality responsible for Generalized Resistance to Thyroid Hormone in a family with this syndrome. DESIGN: Molecular biological studies were performed on a mutant human thyroid hormone receptor beta (hTR beta) cloned from fibroblasts of the patient. PATIENTS: The patient is from a previously reported family with typical features of Generalized Resistance to Thyroid Hormone, demonstrating goitre, elevated thyroid hormone levels, slightly elevated TSH, and retarded bone age. MEASUREMENTS: A cDNA for hTR beta 1 was cloned using specific oligonucleotide primers from fibroblast DNA. A mutant hTR beta 1 expression vector was constructed, and an in-vitro expressed mutant receptor was tested for T3 binding. Receptor binding to DNA was studied in a DNA cellulose assay and gel mobility shift assay. RESULTS: Two mutations were found in the cloned hTR beta. One was silent but the second changed arginine 438 to histidine. The mutation was present in RNA and genomic DNA, as shown by allele specific amplification. The mutated receptor had reduced T3 binding affinity but demonstrated normal binding in a DNA cellulose assay and in a gel mobility shift assay. The receptor did not have altered heat sensitivity. CONCLUSIONS: In the T sibship with Generalized Resistance to Thyroid Hormone, resistance to thyroid hormone is apparently produced by a substitution of a histidine for arginine at amino acid 438, which causes reduced binding of receptor to T3, although the receptor remains able to bind to DNA and, for this reason, functions as a dominant negative in affected subjects who are heterozygous with one normal and one mutated allele. PMID- 8435884 TI - Adjunctive cholestyramine therapy for thyrotoxicosis. AB - OBJECTIVE: Initial therapy of thyrotoxicosis usually includes beta-blockade for symptom relief and thionamides to block new thyroid hormone synthesis. In view of the increased enterohepatic circulation of thyroxine (T4) and triiodothyronine (T3) in thyrotoxicosis, we proposed that cholestyramine, an anion exchange resin which binds iodothyronines, when used adjunctively with thionamides and a beta blocker, would lower serum iodothyronine levels faster than would standard therapy alone. DESIGN: A double blind placebo-controlled cross-over design was used with patients randomly assigned to either the treatment or control groups. They received their initial treatment for two weeks (Phase 1) followed by a one week washout period, and then crossed to the opposite treatment for two weeks (Phase 2). Standard therapy included atenolol 50 mg daily, individualized dosages of methimazole and either 4 g of cholestyramine or 4 g of placebo powder four times per day. PATIENTS: Fifteen patients with thyrotoxicosis (14 Graves' disease, 1 toxic adenoma) participated in this study. MEASUREMENTS: Total and free thyroxine and triiodothyronine, as well as thyroid-stimulating immunoglobulin and thyrotrophin-binding inhibitory immunoglobulin, were measured weekly. RESULTS: Seven patients received cholestyramine and eight patients received placebo during Phase 1. A more rapid decline in all thyroid hormone levels was seen in the cholestyramine-treated group (F = 4-7, P < 0.01) than in the placebo group (F = 2-3.1, P = 0.05). In Phase 2, the eight patients who received cholestyramine showed an additional decline in free thyroxine from weeks one to two, but the overall rate of decline in hormone levels was not different between the groups. Immunoglobulin levels remained unaffected regardless of group, treatment, or time. CONCLUSIONS: We conclude that cholestyramine is a safe and effective adjunctive agent in the treatment of thyrotoxicosis and that its greatest efficacy may be during the first few weeks of treatment. PMID- 8435885 TI - The early effects of radioiodine therapy for hyperthyroidism on biochemical indices of bone turnover. AB - OBJECTIVE: We investigated the early changes following radioiodine therapy for hyperthyroidism, in biochemical indices of bone synthesis and degradation, and their relationship to circulating thyroid hormone concentrations. DESIGN: Prospective follow-up over the first 12 weeks after radioiodine therapy. PATIENTS: Six women with clinical and biochemical evidence of hyperthyroidism. MEASUREMENTS: Serum concentrations of T4, free T3 and osteocalcin, and urinary excretion of the pyridinium cross-links, pyridinaline and deoxypyridinaline, measured before and weekly for 12 weeks after administration of radioiodine therapy. RESULTS: Biochemical indices of bone metabolism were elevated prior to treatment. There was a brisk reduction in circulating thyroid hormones levels paralleled by a similar fall in pyridinium cross-link excretion, which had returned to normal in five patients by the end of the study. There was a positive correlation between pyridinium cross-link excretion and thyroid hormone concentrations. There was no significant change in serum osteocalcin. CONCLUSIONS: Treatment of hyperthyroidism results in prompt correction of the associated increased rate of bone collagen degradation suggesting that effective early correction of hyperthyroidism is desirable to limit its detrimental effect on skeletal mass. PMID- 8435886 TI - Cross-sectional and longitudinal study of the pituitary-thyroid axis in patients with thalassaemia major. AB - OBJECTIVE AND DESIGN: Thyroid dysfunction is known to occur frequently in thalassaemia major, but its prevalence and severity varies in different cohorts, and the long-term natural history is poorly described. We evaluated the pituitary/thyroid axis in thalassaemia major patients in a cross-sectional study and correlated abnormalities with indices of iron overload. Furthermore, the course of thyroid disease in thalassaemia major patients was assessed in a 15 year longitudinal study. PATIENTS AND MEASUREMENTS: Cross-sectional study: pituitary-thyroid axis function was examined in 37 patients (22 F, 15 M; aged 10 39 years, mean +/- SE = 21 +/- 1.4) out of a total of 43 who attended the Haematology and Endocrinology Clinics of Hadassah Hospital on a regular basis. The mean pretransfusion Hb level was 85 +/- 20 g/l, and all patients except one were treated with desferrioxamine (DF, mean +/- SE dose 20.2 +/- 2.6 mg/kg/day). Twenty-two had hypogonadotrophic hypogonadism (HH). Longitudinal study: 21 thalassaemia major patients were evaluated with TRH tests in 1976 and again in 1985. Fourteen of these and another eight were evaluated in both 1985 and 1991. RESULTS: Cross-sectional study: no patient had any clinical signs or symptoms of hypothyroidism; however, one had abnormally low T4, borderline low FT4 and normal T3 levels associated with an exaggerated TSH response to TRH consistent with mild hypothyroidism. This patient did not have a previous TRH test, but serial basal determinations over 7 years revealed a progressive decrease in thyroid function. Thirty-six patients had thyroid hormone levels within the normal range. Nine of these (24.3%) had only an exaggerated TSH response to TRH whereas seven others (19%) also had borderline elevated basal TSH levels. TSH response to TRH was not correlated with age, serum ferritin or liver function tests (ALT or GGT). Longitudinal study: mean TSH response to TRH decreased (P < 0.002), and mean T3 levels increased (P < 0.001) between 1975 and 1985. These findings are probably related to the initiation of DF treatment in 1981. During the last 6 years, four patients with previously normal TSH responses to TRH developed elevated peak TSH levels. Mean T3 concentrations decreased and TSH response to TRH increased significantly (P < 0.001 for both). CONCLUSIONS: (1) In this patient group the thyroid pituitary axis is less sensitive than the gonadal axis to iron-induced damage; only one out of 37 patients developed mild uncompensated hypothyroidism. (2) As opposed to the gonadal axis, the thyroid gland appears to fail before the central components of the axis. (3) Abnormal thyroid function may be reversible in the early stages. (4) Progression is variable, and it may take years to progress from normal to uncompensated hypothyroidism. PMID- 8435887 TI - Increased body fat mass and decreased extracellular fluid volume in adults with growth hormone deficiency. AB - OBJECTIVE: Growth hormone deficiency in adults with hypopituitarism has previously received little attention. Recent data, however, suggest that GH deficiency might be essential for the long-term prognosis of these patients. Earlier studies have documented that GH regulates body composition; in this, body composition in adult patients with hypopituitarism including GH deficiency was studied. DESIGN: A follow-up study of patients with hypopituitarism on routine replacement therapy with L-thyroxine, cortisone acetate and sex steroids. PATIENTS: One hundred and six patients (69 males, mean age 52.5 years and 37 females, mean age 53.4 years) diagnosed as having growth hormone deficiency on the basis of low IGF-I concentration or a maximum GH-response less than 5 mU/l after an insulin/glucagon tolerance test. MEASUREMENTS: Body composition was estimated from body weight, total body water and total body potassium and the results were compared with values predicted from height, weight, age and sex, using data from a large number of healthy subjects. RESULTS: The total body water was significantly lower than that predicted from the observed body weight (P < 0.001), as was the extracellular water (P < 0.001) and the extracellular/intracellular water quotient (P < 0.001). On average, the body cell mass was similar to the predicted value, but the observed/predicted body cell mass ratio correlated positively with age at follow-up. The body cell mass was lower than predicted in subjects below the age of 50 years (P < 0.01). The body fat was higher than predicted (P < 0.001); the increases was also noted in lean subjects. The observed body weight in male subjects was 7.5 kg higher (P < 0.001) than that predicted from healthy subjects of the same body height, a difference explained by an average increase of 6.6 kg in the body fat (P < 0.001) and 1.6 kg in the body cell mass, with a simultaneous reduction of 0.7 kg in the extracellular water (NS). Male patients suffering from untreated androgen deficiency had lower body cell mass than those on androgen treatment. Female subjects weighed 3.6 kg (NS) more on average than healthy women, a difference explained by an increase in the body fat of 6.0 kg (P < 0.001) with a simultaneous decrease of 2.4 kg in the extracellular water (P < 0.001). The body cell mass was similar to that seen in the controls. CONCLUSIONS: Adult patients with growth hormone deficiency have an increased body weight compared to normals of the same age, sex and height, due to an increment of the body fat with a simultaneous reduction in the total body water. PMID- 8435888 TI - Transsphenoidal resection in Cushing's disease: undetectable serum cortisol as the definition of successful treatment. AB - OBJECTIVE: We tested the hypothesis that in Cushing's disease, ACTH secretion from the normal pituitary surrounding an ACTH-secreting adenoma is inhibited and hence removal of the entire adenoma should result in an undetectable serum cortisol in the immediate post-operative period. DESIGN: A retrospective study of patients undergoing transsphenoidal selective adenomectomy, hemi-hypophysectomy or total hypophysectomy for Cushing's disease at St Bartholomew's Hospital between 1985 and 1990. PATIENTS: Forty-eight consecutive patients (33 women, mean age 43, range 7-69 years) undergoing transsphenoidal hypophysectomy for Cushing's disease. Ten patients who underwent a second operation were re-evaluated; the patients were followed for a median time of 40 months after operation (range 15 70). MEASUREMENTS: Post-operatively, serum cortisol was measured daily at 0900 h. Serum TSH, T4, prolactin, LH, FSH, testosterone or oestradiol plus plasma and urine osmolality were measured. RESULTS: After initial surgery, post-operative serum cortisol was undetectable (< 50 nmol/l) in 20 out of 48 patients (42%) and < 300 nmol/l in 32 out of 48 patients (67%). Re-exploration of the pituitary fossa in 10 patients found undetectable cortisol levels in 25 (52%) and levels < 300 nmol/l in 39 (81%) patients. Cushing's syndrome has not recurred, clinically or biochemically, in any patient in whom the post-operative cortisol was < 50 nmol/l. Post-operatively, hypothyroidism was present in 40% of patients and hypogonadism in 53% of men and 30% of premenopausal women. Diabetes insipidus, persisting for at least six months, occurred in 46% of patients. CONCLUSIONS: Cushing's disease has not recurred in any patient with an undetectable serum cortisol (< 50 nmol/l) post-operatively. Serum cortisol should be regarded as a tumour marker in Cushing's disease and the aim of transsphenoidal hypophysectomy for Cushing's disease should be to render the immediate post-operative serum cortisol undetectable. PMID- 8435889 TI - Influence of sex, age and adrenergic pathways on the growth hormone response to GHRP-6. AB - OBJECTIVE: His-dTrp-Ala-Trp-dPhe-Lys-NH2 (GHRP-6) is a synthetic compound that releases GH in a dose-related and specific manner in several species including man. To further characterize the effects of GHRP-6 on GH secretion in normal human subjects, we assessed plasma GH levels following GHRP-6 administration in normal male adult subjects, normal female adult subjects at different stages of their menstrual cycle and in normal prepubertal male and female children. We also studied the influence of adrenergic pathways on GHRP-6 induced GH secretion in normal adult male subjects. DESIGN: In a group of eight volunteers the following tests were carried out: GHRP-6 alone (1 microgram/kg i.v. at 0 minutes); propranolol (40 mg p.o. at -30 minutes) plus GHRP-6; and prazosin (3 mg p.o. at 120 minutes) plus GHRP-6. Another group of eight volunteers were studied with GHRP-6 as above; clonidine alone (300 mg p.o. at -60 minutes); and clonidine plus GHRP-6. A group of nine women were studied with 1 microgram/kg i.v. of GHRP-6 at 0 minutes, at different stages of their menstrual cycle. Finally, 12 children were studied with GHRP-6 using the same dose and methods as above. PATIENTS: Twenty-five normal adult subjects (16 male and nine female) and 12 normal prepubertal children (six male and six female) wer studied after giving informed consent. MEASUREMENTS: Plasma GH levels were measured by radioimmunoassay. RESULTS: No differences in GH responses to GHRP-6 were found between children and normal adult male or female subjects at different stages of their menstrual cycle. Administration of propranolol and clonidine did not modify the GH responses to GHRP-6 in male adults. In contrast, prazosin administration induced an increase in plasma GH levels that was statistically different from that of GHRP-6 alone (. < 0.05 between area under curve). CONCLUSIONS: GHRP-6 exerts a potent stimulatory effect on GH secretion in adults and children. Its effects, at least at the dose studied, are independent of sex and age. Noradrenergic pathways through alpha 2 adrenergic receptors are unlikely to influence this response. PMID- 8435890 TI - The frequency and amplitude of growth hormone secretory episodes as determined by deconvolution analysis are increased in adolescents with insulin dependent diabetes mellitus and are unaffected by short-term euglycaemia. AB - OBJECTIVE: High overnight plasma growth hormone (GH) levels in insulin-dependent diabetes mellitus (IDDM) are reflected in both an increase in the GH pulse amplitude and elevated baseline GH concentrations. To determine whether these are a result of an increase in GH secretory episodes, we undertook deconvolution analysis of overnight GH profiles using previously determined half-life data. DESIGN: Deconvolution of overnight GH profiles (2000-0800 h) was undertaken from normal and diabetic adolescents (either on their usual insulin regime (n = 15), during overnight euglycaemic clamp using a variable rate insulin infusion (n = 29), or during clamp plus 100 mg pirenzepine to suppress endogenous GH (n = 7)). PATIENTS: Thirty-five normal and 29 diabetic adolescents of both sexes at all stages of puberty. MEASUREMENTS: GH secretory rates were calculated from deconvolution analysis, and Fourier transformation was increased mean overnight GH secretion when analysed by sex and by puberty stage compared to normal subjects; overnight GH secretion median (range) of diabetic group 1.88 (0.56 3.81) mU/min; control group 0.62 (0.32-1.92) mU/min (P < 0.001). Fourier transform analysis of these secretory episodes showed greater pulse frequency in the diabetics with dominant pulse periodicity of 90 minutes compared with 135 minutes in normal subjects. During overnight euglycaemia, mean +/- SEM overnight GH secretory rates were comparable to subjects' usual regime night (1.82 +/- 0.33 vs 1.91 +/- 0.37 mU/min) and there was no change in the dominant pulse periodicity of 90 minutes. Pirenzepine administration in diabetic subjects significantly reduced overnight GH secretion from 1.57 +/- 0.19 to 0.71 +/- 0.80 mU/min (P < 0.001) showing a median (range) reduction of 63 (9.3-82.8)% when compared to the subjects' clamp night. However, dominant pulse periodicity was not altered by pirenzepine administration, and remained at 90 minutes. CONCLUSION: In patients with insulin-dependent diabetes mellitus there is an increase in both the amplitude and frequency of pulsatile GH secretion compared to normal subjects, which is not affected by maintenance of overnight normoglycaemia. The anticholinergic drug pirenzepine appears to suppress the amplitude of GH pulse secretion but has no effect on frequency. PMID- 8435891 TI - Analytical and clinical significance of peptide hormone heterogeneity with particular reference to growth hormone and luteinizing hormone in serum. PMID- 8435892 TI - Care for the infertile male. PMID- 8435893 TI - Parathyroid hormone related protein. PMID- 8435894 TI - Five-year follow-up of growth hormone antibodies in growth hormone deficient children treated with recombinant human growth hormone. AB - OBJECTIVE: The aim was to investigate the long-term evolution of circulating growth hormone antibodies (GH-AB) during and after treatment with methionyl recombinant human growth hormone (met-rhGH). DESIGN AND PATIENTS: The investigation was performed on serum samples of 46 growth hormone deficient children, treated for at least 12 months with met-rhGH. Twenty patients had never been treated with hGH (previously untreated patients, Group I). Twenty-six subjects were previously treated with pituitary extracted hGH (treated patients, Group II). MEASUREMENTS: Serum levels of GH-AB were measured by radioimmunoassay using charcoal precipitation of free ligand. RESULTS: Fifteen patients (75%) of Group I and three patients (12%) of Group II developed GH-AB. In 15 GH-AB positive patients the antibodies became detectable during the first year of treatment with met-rhGH. In three patients, however, the GH-AB appeared during the second year. Once present, the GH-AB remained detectable throughout the period of treatment with met-rhGH. In six patients in whom treatment with met rhGH was stopped, GH-AB levels decreased rapidly. In nine patients in whom treatment with met-rhGH was changed to rhGH, the levels of GH-AB decreased and ultimately became undetectable. In two patients GH-AB remained present during administration of rhGH. No effect of GH-AB on the growth-promoting effect of met rhGH could be documented, either during the first or during the second year of treatment. CONCLUSIONS: This study confirms the high immunogenicity of met-rhGH, especially in patients not treated earlier with hGH. Once present, the GH-AB remain detectable throughout the period of treatment with met-rhGH. After stopping met-rhGH treatment or changing to rhGH the GH-AB disappear rapidly in most patients. No effect of GH-AB on the growth-promoting effect of rhGH could be documented. PMID- 8435895 TI - Different modes of growth hormone (GH) administration do not change GH binding protein activity in man. AB - OBJECTIVE: Studies in rodents have shown GH binding protein (GHBP) levels to be dependent on the mode of GH administration. The aim is to determine whether GHBP levels in man are also modulated by the pattern of GH administration. PATIENTS: Six GH deficient subjects participated in a randomized study in which 2 IU GH were administered either as (i) a continuous 24-hour infusion, (ii) two intravenous boluses or (iii) eight intravenous boluses every 3 hours. In a second study, six normal men received a single subcutaneous injection of 0.2 U/kg GH and GHBP activity was measured over 24 hours. Control data were obtained from an untreated group of six age-matched normal men. MEASUREMENTS: GHBP activity was measured by immunoprecipitation using a monoclonal antibody that recognizes the human GHBP, and expressed as percentage specific binding of 125I-GH in 50 microliters of serum. RESULTS: GHBP activity was not significantly different between the GH deficient and normal subjects. GHBP activity did not rise significantly during GH administration with each of the three intravenous patterns of delivery nor were there any significant differences between treatments. In the second study, GHBP activity did not change significantly following subcutaneous GH injection nor did results differ from untreated normal controls. CONCLUSIONS: The level of GHBP in man is not dependent on GH secretory status or altered by short-term GH treatment or the mode of administration. These findings stand in contrast to GH treatment effects in rodents and suggest that GH regulation of GHBP may be different between species. PMID- 8435896 TI - Changes in pituitary response to GnRH during the luteal-follicular transition of the human menstrual cycle. AB - OBJECTIVE: We studied changes in pituitary response to GnRH during the luteal follicular transition of the human menstrual cycle. DESIGN: Normally cycling women were investigated during two consecutive menstrual cycles. In each woman, GnRH tests were performed during the two LH surges and several times during the luteal-follicular transition. Data for analysis were available in all women on days -8, -6, -4, -2, -1, 1, 2, 3, 4, 5 and 7 in relation to the onset of second menstruation (day 1). PATIENTS: Five normally ovulating parous women were studied. MEASUREMENTS: Pituitary response to GnRH was calculated as the net increase in LH and FSH at 30 minutes (delta LH and delta FSH) above the basal value. RESULTS: delta LH and delta FSH showed a similar pattern of significant changes during the luteal-follicular transition. They decreased progressively from days -8 to 1 and increased on day 2. delta LH and delta FSH then decreased on days 3 and 4 and showed a further increase on days 5 and 7. In contrast to these changes, basal FSH levels increased from days -2 to 1 and remained high up to day 5, while basal LH levels showed a trend to increase only after the onset of menses. CONCLUSIONS: These results demonstrate that the increase in basal FSH secretion during the luteal-follicular transition is GnRH independent. It is suggested that LH and FSH release under the stimulation by GnRH is regulated by a common mechanism. PMID- 8435897 TI - Control of prolactin-secreting macroadenomas with parenteral, long-acting bromocriptine in 30 patients treated for up to 3 years. AB - OBJECTIVE: We investigated the effect of intramuscular injections of long-acting bromocriptine in patients with macroadenomas. STUDY DESIGN AND PATIENTS: Thirty patients with PRL-secreting pituitary macroadenomas were treated with repeated 4 weekly intramuscular injections of 50 or 100 mg of a long-acting, repeatable bromocriptine formulation for six to 37 injections, amounting to a total of 473 injections. Twenty patients received parenteral bromocriptine as primary therapy, ten had persisting hyperprolactinemia after previous therapies including pituitary surgery (n = 7), oral bromocriptine (7), and pituitary irradiation (2). MEASUREMENTS: A PRL day profile was obtained and the patients' clinical status and history were documented, at intervals. Detailed clinical, laboratory, and radiological (pituitary nuclear magnetic resonance or computed tomography scan) evaluations were performed at baseline, after 1 injection and every 6th injection thereafter. RESULTS: In all patients PRL was suppressed from a mean +/- SEM pretreatment level of 32,620 +/- 8680 to 4480 +/- 1140 mU/I on the third day after the first injection. In 12 patients PRL levels normalized (< 400 mU/I) with the first to fourth injection, in three additional patients PRL levels normalized after 8-15 months. In 19 patients PRL was suppressed to less than 1000 mU/l. In three patients PRL did not decrease to less than 50% of pretreatment; in two of them on oral bromocriptine prior to this study there had been a comparable low efficacy. Of 28 patients with macroadenomas (median height 22 mm) tumour shrinkage was evident in 15 by nuclear magnetic resonance or computed tomography scan 28 days after the first injection, and in three additional patients after 6 months. There was further regression in seven cases after 12, 18 or 24 injections. Adenoma size (mean +/- SEM) decreased to 66 +/- 7% of the pretreatment value. The 40 adverse events noted in 20 of 30 patients during 24 hours after the first injection were similar to known side-effects of oral bromocriptine, nausea and postural hypotension being the most frequent. With repeated injections, on average 0.6 adverse events were noted per injection (mostly mild asthenia). There were no local adverse reactions at the injection site. CONCLUSION: We conclude that long-acting repeatable bromocriptine in patients with macroprolactinomas offers a safe and efficacious primary treatment that ensures compliance and gives long-term control. Adverse reactions are comparable to oral bromocriptine but subside with repeated injections. PMID- 8435898 TI - Pharmacokinetics of 1-deamino-8-D-arginine vasopressin after various routes of administration in healthy volunteers. AB - OBJECTIVE: We investigated the pharmacokinetics and biological effects of 1 deamino-8-D-arginine vasopressin (dDAVP) in healthy adults after intravenous, subcutaneous, intranasal, peroral, sublingual and intrarectal administration. DESIGN: Eight normal volunteers were studied over an 8-hour period after each drug administration, separated by at least one week. For intravenous and subcutaneous administration, the subjects received 2 micrograms of dDAVP. The intranasal and sublingual doses were 20 micrograms and the rectal dose was 50 micrograms. Oral administration of dDAVP was effected with a 200-micrograms tablet. MEASUREMENTS: Plasma and urinary levels of dDAVP were measured using a specific and sensitive radioimmunoassay. RESULTS: A significant increase of urine osmolality was observed after all routes of administration, except the sublingual and intrarectal for up to 8 hours after administration. After intravenous administration, the half-life of elimination (t1/2) of dDAVP was 78 +/- 10 minutes. An extensive adsorption of dDAVP to the plastic syringe was found with intravenous but not with subcutaneous administration. Using the area under the curve of dDAVP from the subcutaneous administration as a reference, bioavailability was found to be 3.4% after intranasal administration and 0.1% after oral administration. After sublingual and intrarectal routes of administration no detectable dDAVP was found in the blood; however, low amounts were found in the total 24-hour urine. CONCLUSION: The bioavailability of dDAVP seems lower than previously reported after intranasal and oral administration. PMID- 8435899 TI - Congenital hypothyroidism: the Riyadh Military Hospital experience. AB - OBJECTIVE: We aimed to find out the incidence of primary congenital hypothyroidism (CH) among infants born within the Riyadh Al-Kharj Hospital Programme in addition to early detection and treatment of these infants. DESIGN: All babies born within the Riyadh Al-Kharj Hospital Programme were screened by cord blood TSH. Blood spot TSH were done in the majority of infants between 2 and 5 days after birth. All suspected cases were recalled for confirmatory tests. 123I thyroid scan and X-ray of the knee and maternal blood for thyroid antibodies were done for confirmed cases. MEASUREMENTS: A cut off TSH level of 30 mIU/l for cord blood and 25 mIU/l for spot blood were used. All samples were assayed by immunoassay methods. RESULTS: 44,778 (99.4% of the total births) infants were screened. Twenty-five cases were detected, four of which were excluded. The incidence of primary congenital hypothyroidism was 1/2096. Five cases were missed on the initial screen. Eight out of 17 children who had 123I thyroid scan were found to have dyshormonogenesis. Associated malformation and diseases were diagnosed in 42.85%. Two had chromosomal anomalies; ring chromosome 9 has not been previously reported in association with congenital hypothyroidism. CONCLUSION: The incidence of congenital hypothyroidism, dyshormonogenesis and the associated malformations and diseases are higher than those reported in the literature. Cord blood as a screening method is associated with a significant number of missed cases. PMID- 8435900 TI - PCR analysis and sequencing of the SRY sex determining gene in four patients with bilateral congenital anorchia. AB - OBJECTIVE: We explored the possibility of a genetic anomaly in the sex determining region of the Y chromosome, SRY gene, known to be equated to the testis determining region. PATIENTS: Four patients with bilateral congenital anorchia, absence of testicular tissue, elevated FSH and a lack of testosterone response to human chorionic gonadotrophin stimulation tests were studied. MEASUREMENTS: Amplification by polymerase chain reaction of the SRY gene and direct double stranded DNA sequencing were performed with the same primers. RESULTS: The expected 648 basepairs band of SRY was detected in the four DNA samples from patients with bilateral congenital anorchia. Direct sequencing did not show any difference with the previous published sequence. CONCLUSIONS: These data suggest that, in the four patients, bilateral congenital anorchia is not related to an anomaly of the opening reading frame sequence of the SRY gene. PMID- 8435901 TI - Self-administered subcutaneous human menopausal gonadotrophin for the stimulation of testicular growth and the initiation of spermatogenesis in hypogonadotrophic hypogonadism. AB - OBJECTIVE: We determined whether or not self-administered subcutaneous human menopausal gonadotrophin (hMG) therapy is safe and effective in the stimulation of testicular growth and initiation of spermatogenesis in men with hypogonadotrophic hypogonadism where human chorionic gonadotrophin alone had failed. DESIGN: Human menopausal gonadotrophin was self-administered subcutaneously in two dosage regimens to patients requiring (a) fertility (Group I), 37.5 IU twice daily (total weekly dose 525 IU) (n = 7) and (b) increased testicular size (Group II) 37.5 IU once daily (total weekly dose 265.5 IU) (n = 2). Patients were assessed on a monthly basis. PATIENTS: Nine patients with hypogonadotrophic hypogonadism were studied. Six patients had idiopathic isolated hypogonadotrophic hypogonadism, one Kallman's syndrome, one idiopathic isolated hypogonadotrophic hypogonadism secondary to trauma and one with panhypopituitarism secondary to radiotherapy for a hypothalamic pituitary tumour. Five of these patients had a history of unilateral or bilateral cryptorchidism. MEASUREMENTS: Semen analysis and serum testosterone. Testicular size was assessed by use of a Prader orchidometer. RESULTS: Six of seven patients (four with a history of cryptorchidism) requesting fertility attained sperm counts of > 10 million/ml. Three pregnancies have been achieved so far. One failure occurred in a patient with a previous history of cryptorchidism. In Group I patients (a) with an initial testicular volume of 4 ml or less (n = 4), mean size increased from 3.25 +/- 0.9 (SD) ml to 12.2 +/- 3.8 ml, (b) an initial testicular volume of > 4 ml mean size (n = 3) increased from 9.2 +/- 3.9 ml to 10.3 +/- 4 ml. In Group II (n = 2) testis size increased from a mean of 3.0 +/- 1.4 ml to 9.0 +/- 1.4 ml over a 6-months treatment period. CONCLUSION: Self-administered subcutaneous human menopausal gonadotrophin is a safe and effective mode of therapy in increasing testicular size and inducing spermatogenesis in males with hypogonadotrophic hypogonadism. PMID- 8435902 TI - Efficacy of low dose purified FSH in ovulation induction following pituitary desensitization in polycystic ovarian syndrome. AB - OBJECTIVES: We evaluated the efficacy of ovulation induction using purified FSH in either low dose or conventional dosage in patients with polycystic ovarian syndrome. We assessed whether gonadotrophin measurement by radioimmunoassay or immunoradiometric assay is a better indicator of whether pituitary desensitization with a GnRH agonist (Zoladex) has occurred. DESIGN: Two different protocols were used. Pituitary desensitization was carried out with a GnRH agonist (Zoladex, ICI Pharmaceuticals UK). The patients were then randomized into one of two treatment groups. Conventional dose protocol: Patients commenced with a daily FSH (Metrodin, Serono Laboratories Ltd, UK) dose of 75 units for at least 7 days. The FSH dose was then increased, if necessary, based on ultrasound scans and plasma oestradiol (E2) levels in 75-unit increments. Low dose protocol: The same protocol was used except that the starting dose of FSH was 37.5 units daily with increments of 37.5 units. RESULTS: Low dose protocol (six patients, six cycles). There was a high incidence of multiple follicular development (10.3 +/- 5.6 (+/- SD) follicles, 5.0 +/- 3.8 follicles > 14 mm in diameter). Three cycles resulted in ovulation, one was anovulatory and two patients underwent gamete intrafallopian transfer due to multiple follicular development. Conventional dose protocol (seven patients, eight cycles). Again there was multiple follicular development (10.1 +/- 8.6 follicles, 2.0 +/- 2.3 > 14 mm). Three cycles were ovulatory, one anovulatory, three abandoned due to multiple follicular development and one underwent gamete intrafallopian transfer with the development of severe hyperstimulation necessitating steroid therapy. There was no difference between the two protocols in the number of days of FSH administration (low dose protocol 26 +/- 6.5, conventional dose protocol 23 +/- 8.1 days), the total number of units of FSH given per patient was 2844 +/- 1816 vs 2635 +/- 1726. The peak E2 level (pmol/l) during FSH treatment was 3193 +/- 662 vs 2389 +/- 3099 and the rate of increase in the FSH dose in ampoules of Metrodin per day was 0.058 +/ 0.03 vs 0.057 +/- 0.03. All patients were 'downregulated' (E2 < 70 pmol/l) prior to ovulation induction. However, gonadotrophin levels (IU/l) were 4.3 +/- 1.5 (LH) and 2.8 +/- 1.2 (FSH) by radioimmunoassay and LH was unchanged throughout FSH treatment whereas LH measured by immunoradiometric assay was < 1.0 IU/l prior to ovulation induction and remained so throughout. The mean LH radioimmunoassay to immunoradiometric assay ratio was 6.2 +/- 2.1. CONCLUSIONS: We conclude that regardless of the starting dose the use of pure FSH in patients with polycystic ovarian syndrome whose LH has been completely down regulated may be associated with multiple follicular development and a poor outcome. LH measured by radioimmunoassay is not a good indicator of whether pituitary densensitization has occurred but LH measured by immunoradiometric assay appears to be. These results strongly suggest that a basic minimum amount of LH is necessary for normal ovulatory development. PMID- 8435903 TI - Hyperinsulinaemia in the polycystic ovary syndrome confirmed with a specific immunoradiometric assay for insulin. AB - OBJECTIVE: Hyperinsulinaemia in the polycystic ovary syndrome (PCOS) has previously been defined using polyclonal radioimmunoassays (RIA) in which partially processed insulin-like molecules cross-react. This study aimed to reassess hyperinsulinaemia in women with PCOS using specific immunoradiometric assays (IRMA) for insulin, proinsulin and 32-33 split proinsulin. DESIGN: Patients attended for 75 g oral glucose tolerance tests and were divided into groups depending on their degree of obesity and fasting insulin status determined by RIA. IRMA measurements for insulin-like molecules in plasma from patients with PCOS and controls were compared. PATIENTS: Thirty-four patients with ultrasound diagnosed PCOS presented to a reproductive endocrinology clinic. A control group comprised women with normal ovaries on ultrasound. Four groups were constructed, two with normal fasting insulin concentrations (lean PCOS and controls) and two with hyperinsulinaemia (lean and obese PCOS). MEASUREMENTS: Plasma glucose, insulin (RIA and IRMA), proinsulin and 32-33 split proinsulin concentrations were measured at time 0, 30 and 120 minutes of an oral glucose tolerance test. RESULTS: Hyperinsulinaemia determined by RIA in lean and obese women with PCOS was confirmed using a specific IRMA assay for insulin. Plasma proinsulin and 32 33 split proinsulin concentrations were higher in hyperinsulinaemic women with PCOS compared with women with normal insulin concentrations. The proportion of circulating insulin-like molecules represented by proinsulin and 32-33 split proinsulin was similar in all groups studied. CONCLUSIONS: Hyperinsulinaemia in PCOS is likely to reflect insulin resistance because the raised concentrations of proinsulin and 32-33 split proinsulin were in proportion to the raised insulin concentrations. Hyperinsulinaemia in PCOS, defined by RIA, therefore differs from that in non-insulin dependent diabetes mellitus where it is largely accounted for by disproportionate hyperproinsulinaemia. PMID- 8435904 TI - Photodynamic therapy in dermatology: recent developments. AB - The application of PDT in dermatology has been limited by technical problems, lack of standardized treatment parameters and controlled clinical trials, and cutaneous photosensitivity. PDT requires specially trained personnel and relies on devices that are expensive and difficult to maintain. In North America, PDT is currently performed at only a few centers on an investigational basis. Although a great deal of anecdotal clinical information is available on PDT for treating non melanoma skin cancer, controlled trials are still needed in order to compare PDT with the highly effective methods already available. PDT may also be useful for a variety of nononcologic dermatoses. New photosensitizers such as BPD-MA, NPe6, and ALA offer the promise of causing significantly less prolonged photosensitivity than the currently available agents; combined with well-designed clinical studies, this will undoubtedly facilitate the acceptance of PDT into standard dermatologic practice. PMID- 8435906 TI - Acitretin and etretinate. How and when they should be used. AB - Nearly two decades after the advent of synthetic retinoids for the treatment of many severe and incapacitating dermatologic conditions, the usefulness of these drugs is not universally accepted. The safety profile is well established. Other than teratogenicity, which can be avoided if the recommended precautions for use are followed, serious or unexpected adverse reactions rarely occur. This article concisely addresses some questions about etretinate and acitretin therapy that are most pertinent for the dermatologist. PMID- 8435905 TI - Topical retinoids. Their uses in dermatology. AB - The retinoids provide an important new way of treating dermatologic disorders. They have also proved to have a role in the prevention of new lesion formation. New retinoids, of which adapalene is one, have recently been synthesized in order to obtain similar or better efficacy while reducing skin irritation potential. These new molecules are currently under clinical investigation. Preliminary results are encouraging. In the near future, an expanded range of topical retinoids should be available. PMID- 8435907 TI - TARS. Their role in the treatment of psoriasis. AB - The clinical experience reported by these studies does not definitively answer the question of whether or not all or even most tars are effective in the treatment of psoriasis. Information supports both views. With the present data, the following statements seem appropriate: 1. Tar alone may be helpful for a subset of individuals with mild to moderate psoriasis. Because the majority of patients with psoriasis have less than severe disease, this group numerically represents the majority of office-treated patients. For these patients, tars are not unreasonable to use in appropriate clinical circumstances. 2. Crude coal tar is not likely more beneficial than modified tar or gels. These latter preparations have much better patient acceptance and compliance because of decreased odor, staining, and messiness. 3. Overall, the potential severity of side effects from tars is less than that from anthralin and much less than that from topical corticosteroids (atrophy, rebound). 4. Clinical experience confirms that tar preparations can be effective when other modalities fail or cannot be used for reasons of adverse effects or otherwise. 5. Tar shampoos are considered useful therapeutic agents for active clearing therapy and for maintenance. 6. When combined with suberythemogenic ultraviolet light B, tar can be a useful agent. It has fewer side effects in terms of burning and irritation than does aggressive ultraviolet B therapy alone. The effect of maximal erythemogenic ultraviolet light B therapy is not enhanced with tar. Practically speaking, however, the majority of psoriatic patients do not require, or are not able to avail themselves of, convenient controlled ambulatory ultraviolet light therapy. PMID- 8435908 TI - Calcipotriol. A new topical antipsoriatic. AB - Calcipotriol is a synthetic vitamin D analogue. In vitro it can regulate cell differentiation and proliferation and suppress lymphocyte activities. These actions of calcipotriol at the cellular level are very similar to those of the natural hormone 1,25-(OH)2-D3. In contrast, the systemic effects on calcium and bone metabolism are at least 100 to 200 times less than those of 1,25-(OH)2-D3. Because of this unique pharmacologic profile, calcipotriol has been evaluated for the topical treatment of psoriasis. In well-designed and properly conducted studies involving more than 3000 patients, calcipotriol ointment, 50 micrograms/g, has been shown to be effective and safe for the short- and long term treatment of psoriasis vulgaris. Calcipotriol ointment should be applied twice daily in amounts up to 100 g/week (Table 1). Used according to these guidelines, calcipotriol treatment does not affect calcium or bone metabolism. Calcipotriol is indicated for the treatment of plaque-type psoriasis vulgaris and has already been approved in several countries. It should be considered a first line drug for the topical treatment of psoriasis. PMID- 8435909 TI - Liposomes. A perspective for dermatologists. AB - We believe that it is unlikely that intact liposomes can cross the stratum corneum and act as carriers of drugs through the skin. However, it is probable that liposomes have the potential to modify the cutaneous biodistribution of applied chemicals (e.g., drugs, toxins, humectants) and thus modify their activity. Liposomal lipids can also penetrate the skin barrier. The effect of this is likely to be varied and lipid dependent, but this phenomenon could hold the most potential for the application of liposomes to topical therapy. PMID- 8435910 TI - Lasers: state of the art in dermatology. AB - The unique properties of lasers create an enormous potential for specific therapy of skin diseases. As with any new device, the most efficacious and appropriate use requires an understanding of the mechanisms of light interaction with tissue as well as the properties of the laser itself. Modification of current lasers and innovative advances with biomedical laser instrumentation may eventually allow the physician to match optimally the laser and the treatment procedure with the lesion. PMID- 8435911 TI - The new corticosteroids: are they effective and safe? AB - We cannot as yet fully answer the question of the safety of the new corticosteroids. Budesonide is frequently found to be an allergen now that it is being marketed, and it can certainly serve as a primary sensitizer. For the other new corticosteroids, too, we already had numerous positive tests even before they were marketed. This must be considered cross-sensitivity. We will have to wait to see whether or not they are primary sensitizers. For the pharmaceutical industry, there is one more challenge in the development of new corticosteroids: In addition to finding more effective corticosteroids with the fewest "classic" side effects, the industry will also have to identify the least sensitizing molecules. PMID- 8435912 TI - The staphylococci. Importance of their control in the management of skin disease. AB - For skin diseases such as impetigo and furunculosis in which infection with S. aureus is the primary pathologic event, control of that infection is obviously paramount in the management of the clinical situation. The available antistaphylococcal agents are highly effective, and topical mupirocin has been a valuable recent addition. In conditions such as AD the position is less clear. Because the presence of the underlying disease is a prerequisite for the staphylococcal colonization, the exact role of staphylococcal damage is difficult to separate from the underlying disease activity. The definitive experiment, whereby staphylococcal colonization is eradicated over a prolonged period of time by a nonirritant method, remains to be performed. Until that time it is reasonable to pursue a policy of treating S. aureus colonization when it is believed to be of clinical significance and not simply on the basis of bacteriologic findings. PMID- 8435913 TI - Wound dressing. AB - Dressings are applications for wounds, burns, and ulcers. Dressings should be regarded as supportive of healing; they are desirable but not essential in an emergency. This article reviews measurement of wound healing and the functions of wound dressings. A variety of dressings and their respective advantages and disadvantages are discussed. PMID- 8435914 TI - Psychotropic agents in dermatology. AB - In this article, relatively detailed explanation of the use of selected psychopharmacologic agents is given along with their dermatologic and psychodermatologic indications. For a more complete description of the use of these medications, the reader is advised to consult standard textbooks on psychopharmacology and the Physician's Desk Reference. It should be emphasized that psychiatric consultation should be obtained whenever feasible. Yet for a significant proportion of psychodermatologic patients who refuse psychiatric input, the judicious use of these medications may provide much-needed assistance in their recovery from psychodermatologic disorders. PMID- 8435915 TI - Management of vitiligo. AB - Vitiligo is a disease of unknown origin that causes destruction of melanocytes in the skin, mucous membranes, the eyes, and occasionally in hairbulbs and in the ears. The loss of melanocytes alters both structure and function of these organs. The goals of therapy are multifold. The primary goal is to restore melanocytes to the skin so that the epidermis has a normal morphology. Such repigmented skin regains its normal immune/inflammatory functions. PMID- 8435916 TI - Alopecia areata. Update on therapy. AB - The treatment of alopecia areata has changed markedly in the past decade. Several options are now available to the patient. It is the dermatologist's duty to inform the patient of all the options, their side effects, and their success rates. The final selection of treatment is a team decision between the patient, the patient's family, and the physician. PMID- 8435917 TI - Management of hair loss in women. AB - Hair loss in otherwise healthy women presents several challenges for the clinician. The first is to identify the cause, which may be complicated by two or more secondary factors; the second is to find effective treatments; and the third is to establish requirements for long-term management. An optimal hair growth potential is considered to exist when specific parameters for biochemical variables are operating. These include red blood cell and serum folate concentrations within the normal range, serum vitamin B12 levels between 300 and 1000 ng/L, hemoglobin levels greater than 13.0 g/dL, and serum ferritin concentrations of 70 ng/mL or greater. The two predominant disturbances, diffuse androgen-dependent alopecia and chronic telogen effluvium, both require months of treatment before the benefits can be seen. During this time several follow-up investigations and reassuring consultations must occur. Current systemic antiandrogen regimens are highly effective, but the prospect of long-term therapy, possibly for life, is daunting. For some patients there is no systemic choice and topical treatment is the only option. Minoxidil is the only topical preparation currently licensed, but with no quantitative long-term data available, assessing its value in the long-term treatment of androgen-dependent alopecia is difficult. PMID- 8435918 TI - Minoxidil. Update on its clinical role. AB - The study and common use of minoxidil have legitimized research in common baldness. Prior to this time, with rare exception, the field was dominated by charlatans and "snake oil merchants." Minoxidil has opened the door to scientific inquiry and allowed support of serious laboratory investigation. Minoxidil is the first "generation" of hair-growing agents. We hope that succeeding generations will fulfill our wildest tonsorial dreams. PMID- 8435919 TI - The antiandrogens. When and how they should be used. AB - This article is a useful guide for treating androgen-related skin disorders such as androgenetic alopecia, acne, and hirsutism. All available antiandrogens are discussed, as well as treatment doses, efficacy, and mode of action. PMID- 8435920 TI - Immunosuppressive agents in dermatology. AB - Azathioprine, cyclophosphamide, and cyclosporine are immunosuppressive agents commonly used by dermatologists. Azathioprine has a good safety profile and is preferred by most dermatologists for the treatment of bullous pemphigoid, cutaneous vasculitides, chronic eczematous dermatitides, and cutaneous manifestations of connective tissue diseases. For more fulminant diseases such as Wegener's granulomatosis, lymphomatoid granulomatosis, severe cases of systemic lupus erythematosus, or pemphigus, cyclophosphamide is more effective and its use is justified even though it is more toxic. Cyclosporine has been shown to be effective in a variety of dermatoses; the most promising results are seen in psoriasis, lichen planus, pyoderma gangrenosum, and chronic eczematous dermatitides. The long-term safety of cyclosporine remains to be determined, and it should be used judiciously with careful evaluation of the risk-benefit ratio in each case. Dermatologists who use immunosuppressive agents should be familiar with their indications, side effects, dosage, and monitoring. PMID- 8435921 TI - Photoaging and the skin. The effects of tretinoin. AB - The appearance of photoaged skin is cosmetically unacceptable to many in our society. Ostensibly, avoidance of ultraviolet light and sunlight from early childhood is most desirable but not likely to happen in our culture. Tretinoin is the only pharmacologic compound shown to partially reverse some signs of photoaging. Improvement with tretinoin therapy has been quantified clinically and histologically. A major degree of improvement occurs in 6 to 12 months, and maintenance treatment one to three times per week may continue this response. Tretinoin therapy should optimally be used with daily moisturizer and sunscreen applications. Psychosocial benefits of tretinoin therapy, use of tretinoin for intrinsically aged or non-Caucasian skin, and higher-strength tretinoin therapy for severely photoaged skin need to be further explored. It is possible that some subsets of patients with photoaged skin may respond better than others. PMID- 8435922 TI - Adult cardiologists or hyperlipidemia experts have advocated no screening and no treatment for children with familial hyperlipidemia. PMID- 8435923 TI - Ventricular arrhythmias in patients recovering from myocardial infarction: do residual myocardial ischemia and anti-ischemic medical intervention influence the one-month prevalence? The Danish Study Group on Verapamil in Myocardial Infarction. AB - The relationship between myocardial ischemia revealed by exercise testing and ventricular arrhythmias on Holter monitoring, and the effect of anti-ischemic intervention on the incidence of ventricular arrhythmias in patients with residual ischemia were studied in 125 patients recovering from myocardial infarction. Prior to discharge exercise testing and 24-h Holter monitoring were carried out. In patients with ST-segment depression (n = 34), ventricular arrhythmias on Holter monitoring were seen in 7 (21%) compared with 20 (22%) patients without ST-segment depression (NS). Patients were hereafter double blindly randomized to intervention with verapamil (n = 63) or placebo (n = 62). One month after discharge, 24-h Holter monitoring was repeated. In the verapamil group ventricular arrhythmias increased from 25 to 33% (NS). In the placebo group the figures were 18 and 27%, respectively (NS). In patients with ST-segment depression and verapamil treatment, the prevalence increased from 25 to 38% (NS). In the placebo group the figures were 17 and 22%, respectively (NS). The differences between the groups were not significant. A significantly increased prevalence of ventricular arrhythmias was found in patients with either heart failure or non-Q-wave infarct. In these patients myocardial ischemia during exercise did not correlate with ventricular arrhythmias either. ST-segment depression during pre-discharge exercise testing correlated with neither the prevalence nor the incidence of ventricular arrhythmias, and anti-ischemic intervention with verapamil did not influence the incidence of ventricular arrhythmias in both patients with and without myocardial ischemia. PMID- 8435924 TI - Unstable angina: relationship of clinical presentation, coronary artery pathology, and clinical outcome. AB - Patients with unstable angina are heterogeneous with respect to presentation, coronary artery morphology, and clinical outcome. Subclassification of these patients based on clinical history has been proposed as a means of identifying individuals at increased cardiac risk. We applied such a classification system to 129 patients discharged from a coronary care unit with a diagnosis of acute myocardial ischemia. Patients were then assessed for cardiac events (recurrent angina requiring revascularization, myocardial infarction, death) 12 months following hospital discharge. Patients were classified as recent onset unstable angina preinfarction (n = 42), crescendo unstable angina preinfarction (n = 48), and unstable angina postinfarction (n = 39). Within each of these groups, the patients were further subclassified based on the occurrence of angina on effort, at rest, or both. No attempt was made to subset patients taking anti-ischemic drugs at the time of clinical presentation to the physician. Coronary angiographic pathology (morphology and number of vessels involved) was similar in the subgroups, but coronary artery thrombus was statistically more likely to be found in patients with crescendo rest angina preinfarction or with frequent anginal episodes at rest postinfarction. Mortality was significantly higher for patients with unstable angina postinfarction (7.7%) than preinfarction (1.1%). No statistical differences were noted between the subgroups with respect to the occurrence of myocardial infarction or recurrent unstable angina requiring revascularization. These data suggest that subclassification of unstable angina patients based on clinical characteristics at presentation is not useful to predict subsequent myocardial infarction or recurrent angina requiring revascularization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8435925 TI - Differences of intravenous nitroglycerin responses in left ventricular systolic and end-diastolic pressures and coronary artery diameters during long-term treatment with cutaneous nitroglycerin patches. AB - The differences of intravenous nitroglycerin responses in left ventricular (LV) systolic and end-diastolic pressures and in coronary artery diameters (cross tolerance) were investigated in patients receiving nitroglycerin patches. During diagnostic cardiac catheterization, graded doses of 50, 100, and 150 mcg of intravenous nitroglycerin were given. Left ventricular systolic and end-diastolic pressures and left coronary arteriograms were obtained during each dose. Twenty patients with coronary artery disease were studied. Before cardiac catheterization, 10 received nitroglycerin patch (patch group), and 10 did not (control group). In the control group, graded intravenous nitroglycerin doses of 50, 100, and 150 mcg caused decrease in LV systolic pressure of 18 +/- 7%, 20 +/- 5%, and 23 +/- 6%, respectively. In the patch group, the same intravenous nitroglycerin doses decreased LV systolic pressure by 12 +/- 6% (p < 0.05), 19 +/ 7% (NS), and 18 +/- 6% (p < 0.05), respectively, (p value: vs. control group). At the same intravenous nitroglycerin doses, LV end-diastolic pressures were decreased by 48 +/- 14%, 52 +/- 17%, and 56 +/- 9%, respectively, in the control group. However, there were no significant differences in LV end-diastolic pressure between the two groups for any of the three intravenous nitroglycerin doses. The same intravenous nitroglycerin doses caused increase in diameter of the left anterior descending coronary artery and circumflex coronary artery in the control group, which was attenuated significantly in the patch group. Tolerance may develop in LV systolic pressure and coronary artery diameters, whereas it may not develop in LV end-diastolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8435926 TI - Limited value of anaerobic threshold for assessing functional capacity in patients with heart failure. AB - Exercise tolerance was assessed in 146 patients with cardiac dysfunction in terms of anaerobic threshold (ATge). Patients were divided into four classes according to the peak oxygen uptake: Class A (72 patients) exceeding 1000 ml/min; Class B (27 patients) 800-999 ml/min; Class C (37 patients) 500-799 ml/min; and Class D (10 patients) below 500 ml/min. An incidence of the ATge breakpoint was lower in patients of Class C (38%) than in those of either Class B (70%, p < 0.05) or Class A (87%, p < 0.05). The ATge could not be determined in any patients in Class D. The V-slope method improved the ability to determine ATge by 20%. In Classes C and D, ATge detection was precluded considerably by the fact that the initial workloads of exercise test involved oxygen uptake levels already close to or above the ATge. An oscillatory hyperventilation pattern was also significantly related to failure in defining ATge in Class C patients. Of the 51 patients whose ATge was undetermined, 9 had an atrial septal defect. In two of these, exercise induced right-to-left shunting led to progressive arterial hypoxemia, and the consequent hyperventilation masked the appearance of ATge. Thus, ATge is virtually undetectable in patients with severe heart failure largely because of the early onset of anaerobic metabolism or abnormal ventilatory responses to exercise. Accordingly, the clinical application of ATge in the assessment of functional capacity would be limited to patients with mild to moderate heart failure. PMID- 8435927 TI - Idiopathic verapamil-sensitive sustained left ventricular tachycardia. AB - Idiopathic verapamil-sensitive left ventricular tachycardia (VT) has characteristic QRS configurations during VT: right bundle-branch block with either left axis or right axis (less common) deviation. QRS duration is relatively narrow (0.13-0.16 s) and frequently endocardial activation prior to QRS is recorded during VT, which is the basis of its being called fascicular tachycardia. The mechanism is probably reentry, but the nature of the slow conduction necessary for the occurrence of reentry is quite different from that of other sustained monomorphic VT associated with structural heart disease. Chronic oral verapamil therapy is the drug of choice for alleviation of symptoms. Long-term prognosis is good. PMID- 8435928 TI - Acute myocardial infarction with ventricular septal rupture. AB - The interventricular septum is one of the three main sites at which the myocardium can rupture. The features of the interventricular septal rupture that occurred in a 72-year-old woman are characteristic of interventricular septal ruptures in general: (1) they occur most commonly in elderly women; (2) the most common site is the mid-portion of an acute, transmural anteroseptal apical infarct; (3) they are also most common during the patient's first heart attack; (4) the clinical diagnosis of acute myocardial infarct is confirmed by both ECG and by serum enzyme levels; (5) the usual time of the rupture is 3-10 days after the onset of the infarction (it occurred after 3 days in our patient); (6) a new cardiac murmur usually is heard and the patient frequently goes into shock; (7) the diagnosis can be confirmed by a step-up in pO2 levels from right atrium to right ventricle; (8) the usual cause is severe old coronary atherosclerosis with a recent thrombotic occlusion as the final precipitating event. PMID- 8435929 TI - Transesophageal echocardiography in the diagnosis of acquired aneurysms of the left atrial appendage. PMID- 8435930 TI - Late thrombotic obstruction of an aortic bioprosthetic valve: successful treatment by oral anticoagulation. AB - Thrombotic obstruction of aortic bioprostheses is rare. Few cases have been reported involving the use of the Carpentier-Edwards (CE) prosthesis, the Hancock bioprosthesis, or the Medtronic Intact porcine valve. Thrombolytic therapy for mechanical valve thrombosis has been used frequently even though it is known to carry a high risk of embolism and recurrence. However, the use of this therapy was reported for the first time only recently, in a case of acute aortic thrombosis which occurred 3 1/2 months after bioprosthesis insertion. We report a case of late progressive thrombotic obstruction of a CE aortic valve 3 years after insertion. The case was successfully treated with coumadin therapy, as confirmed by serial Doppler echocardiographic examinations and a 3-year follow up. PMID- 8435931 TI - Coronary artery-right ventricular fistula after coronary artery bypass grafting. AB - Development of a coronary artery fistula rarely occurs after cardiac surgery. We report the appearance of a coronary artery-right ventricular fistula as a consequence of coronary artery bypass grafting. Possible mechanisms and consequences are discussed. PMID- 8435932 TI - Embolic stroke: are we missing the source in many young patients? PMID- 8435933 TI - New directions in myocardial perfusion imaging. AB - In recent years, substantial progress has been made in the field of nuclear cardiology. Pharmacologic stress perfusion imaging with intravenous administration of dipyridamole or adenosine provides comparable sensitivity and specificity values for detection of coronary artery disease (CAD) as exercise imaging and has been employed successfully for risk stratification prior to peripheral vascular or aortic surgery and after myocardial infarction. Detection of myocardial viability can be enhanced utilizing reinjection of a second dose of thallium-201 (Tl-201) at rest after acquisition of redistribution images with the single photon emission computerized tomography (SPECT) technique. Imaging solely in the resting state with Tl-201 can also provide information concerning presence of viable myocardium in asynergic regions that are stunned or hibernating. New technetium-99m (Tc-99m) perfusion agents have emerged in the clinical setting and have provided excellent predictive value for detection of CAD in patients with chest pain and permit simultaneous assessment of function and regional blood flow. Tc-99m Sestamibi, one of these agents, is also a valid marker of viability when assessing myocardial salvage after coronary reperfusion in acute myocardial infarction. PMID- 8435934 TI - Cardioprotection with angiotensin-converting enzyme inhibitors: redefined for the 1990s. AB - The concept of "cardioprotection" with ACE inhibitors has evolved over the last decade. In the 1980s, protective benefits of ACE inhibitors in hypertension were established, regression of left ventricular hypertrophy was demonstrated, and improved ventricular function and survival in mild-to-moderate and severe congestive heart failure was documented. A further "protective" role of ACE inhibitors in coronary artery disease is emerging as more attention is focused on the concept of local tissue renin-angiotensin systems. Recent contributions to the literature describe significant benefits of ACE-inhibitor therapy in acute myocardial infarction, including suppression of ventricular arrhythmias and reduction of both early and late ventricular dilation, preservation of left ventricular function, and improved survival. All of the above effects can be considered "cardioprotective." However, as new benefits are reported in the 1990s, a broadened view of "cardiovascular protection" emerges from investigative studies in the literature. ACE inhibitors may reduce tolerance to nitrates, reduce angina in some but not all studies, and limit smooth muscle cell proliferation (and perhaps restenosis) induced by experimental balloon angioplasty. Local vascular effects may attenuate atherosclerotic changes in the arterial wall in experimental animals and may decrease the incidence of aneurysm formation in hypertensive animals. The effectiveness of ACE inhibitors in acute myocarditis, suggested by reports that captopril may reduce lesions of murine myocarditis when administered early after infection with coxsackievirus B3, requires clinical confirmation. Despite these apparently diverse "cardiovascular protective" consequences of ACE inhibitor therapy, the mechanism(s) of action of these agents remain to be elucidated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8435935 TI - Vaginal flora in health and disease. AB - This chapter has portrayed the normal vaginal flora as a range of microbial species that associates in a stable way with human vaginal epithelium. The human vagina provides these microorganisms with the physical and chemical environment that allows them to use this tissue as a normal habitat. Because the relationship of the normal flora to the underlying tissue is that of an ecosystem, the components of this system are in dynamic equilibrium. Consequently, a change in the environmental conditions provided by the vaginal epithelium will result in changes in the population density or the species composition of the normal flora. Although the microbial flora appears to provide a benefit to the host by reducing the probability of colonization by exogenous microorganisms, it may participate in various undesirable symptoms, including various types of vaginitis or postoperative, postabortion, and post-Caesarean section infections, and upper tract invasion after lower tract infection. All future attempts to understand vaginitis in all its manifestations necessarily must include recognition of the importance of the normal flora because all types of vaginitis are superimposed on an existing endogenous microbial flora. PMID- 8435936 TI - Immunology of the vagina. PMID- 8435937 TI - Vulvovaginal conditions mimicking vaginitis. PMID- 8435938 TI - Trichomonas vaginalis: a reemerging pathogen. AB - Infestation with T. vaginalis is a common and potentially morbid infection. In addition to reproductive tract discharge and irritation, infection with this protozoa is increasingly recognized to be associated with reproductive tract complications, including postabortal infection, postcesarean infection, preterm birth, and PROM. Clinical diagnosis is often difficult and newer approaches using specific antigen and nucleic acid technologies will probably replace "wet prep" microscopic techniques. Effective treatments continue to depend on oral metronidazole treatment. Cure of resistant strains, which remain rare, depends on administration of higher, more prolonged doses of metronidazole. Improved understanding of the natural history, pathobiology, diagnosis, and treatment of this common protozoa is urgently needed. Practitioners should consider routinely screening and treating women for trichomoniasis before any reproductive tract surgery (chorionic villi sampling, hysterectomy, cesarean section, dilatation and curettage, therapeutic abortion, and so on), after changing sexual partners, and during pregnancy. Both symptomatic and asymptomatic patients and their sexual contacts should be treated. PMID- 8435939 TI - Pathogenicity of Trichomonas vaginalis. PMID- 8435940 TI - Candidal vulvovaginitis. PMID- 8435941 TI - Bacterial vaginosis. PMID- 8435942 TI - Herpetic vaginitis in 1993. AB - Substantial advances have been made in our understanding of HSV and genital herpes. The molecular biology of viral structure and function and the pathogenesis of infection have been elucidated to a large degree, and epidemiologic investigations, based on reliable type-specific assays, have been done. Diagnostic techniques have been refined, and the value of therapy has been defined. Currently, management strategies for pregnant women and their neonates are based on data rather than hypothesis, and rational counseling is feasible. The next major advance in the field would be the availability of a safe and effective vaccine, the development and investigation of which is being pursued vigorously. PMID- 8435943 TI - Management of vulvovaginitis in pregnancy. PMID- 8435944 TI - The management of obscure or difficult cases of vulvovaginitis. PMID- 8435945 TI - "Normal" umbilical arterial and venous acid-base and blood gas values. AB - Study groups often considered representative of entire populations inevitably do not consider normal fetuses because nonpathologic events can alter the study parameters. Therefore, the term "normal" and its range, when used for comparisons, must be scrutinized by the obstetrician, pediatrician, and those with medicolegal concerns. PMID- 8435946 TI - Maternal-fetal acid-base physiology. PMID- 8435947 TI - Umbilical cord blood acid-base values and other descriptors of fetal condition. PMID- 8435949 TI - The relationship of asphyxia in the mature fetus to long-term neurologic function. AB - Asphyxia may occur before or during labor in the preterm or term fetus. The development of neuropathologic lesions depends on the degree and duration of the asphyxia. Anoxia may occur, but because of the short duration of the fetal response, it usually will cause the death of the fetus. The common mechanism leading to neuropathologic lesions in the fetus is a significant degree of hypoxia present for a particular period of time. Antepartum asphyxia will cause such lesions and deficits in children. What is missing are measures to establish the prevalence of antepartum asphyxia in a large population and the epidemiologic studies to determine the association between the asphyxia so documented and the deficits in surviving children. The prevalence of intrapartum fetal asphyxia is of the order of 2%. Most of these children will have no evidence of brain damage. The key is the fetal cardiovascular compensatory response that maintains cerebral blood flow and oxygen metabolism. This compensatory phase, subject to the severity of the hypoxia, may continue for several hours. In the clinical setting during labor, this provides the "window of opportunity" when a specific blood gas and acid-base diagnosis can be made, and with appropriate intervention, brain damage can be avoided. However, if the hypoxia persists, a threshold will be reached when fetal cardiovascular decompensation will occur. The compromised cerebral oxygen metabolism will result in brain damage and deficits in the children who survive. The threshold at which brain damage may occur is when the acidosis is severe (pH, < 7.0). At this time, systemic hypotension may occur.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8435948 TI - Correlations between obstetric clinical events and umbilical cord blood acid-base and blood gas values. AB - Umbilical cord blood acid-base analysis may be used to assess the condition of fetus and newborn more objectively. Newborn acid-base status is an important criterion when we attempt to define perinatal asphyxia. It also has medicolegal ramifications because it enables the documentation of the presence of a biochemical milieu that is not related to the later development of cerebral palsy. We anticipate future research will focus on the redefinition of acidemia and its relationship to fetal and new-born outcomes. PMID- 8435950 TI - The practical implications of cord blood acid-base studies. PMID- 8435951 TI - Cord blood gas studies: a survey. PMID- 8435952 TI - Is the appendix where you think it is--and if not does it matter? AB - For over 100 years the recognized surface marking for the appendix has been McBurney's point (the junction of the lateral and middle thirds of a line joining the umbilicus with the right anterior superior iliac spine (ASIS)). In order to test its validity, the relationship between McBurney's point and the appendix was determined on 275 double contrast barium enemas (DCBE). A wide spread of distribution of the site of the appendix base was seen. Only 35% of appendix bases were found to lie within 5 cm of McBurney's point, and 15% were more than 10 cm distant. Seventy-five per cent of appendix bases were below and medial to a line joining the umbilicus with the right ASIS. These findings are in agreement with world-wide studies conducted by the World Organisation of Gastroenterology which showed that less than half of all patients with appendicitis have tenderness maximal over McBurney's point. A record was also made in 93 cases of the position of the appendix in relation to the caecum. The importance of these results in the diagnosis and management of patients with suspected appendicitis is discussed. PMID- 8435953 TI - Congenital diaphragmatic hernia--a review of pre- and postoperative chest radiology. AB - The clinical and pre- and postoperative radiographic features of 63 babies who presented with congenital (Bochdalek) diaphragmatic hernias were reviewed. Fifty five babies presented in the neonatal period and eight in later childhood. For neonatal presenters, the preoperative radiographic features were typical in all cases but one (presented with persistent right pleural effusion). Features associated with a poorer prognosis included the presence of a contralateral pneumothorax, absence of contralateral aerated lung and an intrathoracic site for the stomach. Identification of ipsilateral aerated lung was associated with survival in all cases. Typical postoperative features included an ipsilateral pneumothorax, gradual expansion of the lung, gradual elevation of the hemidiaphragm and pleural effusion. Follow-up films demonstrated reduced vascularity in the ipsilateral lung which was commonly smaller than the contralateral lung. The postoperative radiographic features for delayed presenters differed in that lung expansion was usually complete on the first postoperative radiograph and there was no radiographic evidence of pulmonary vascular hypoplasia. PMID- 8435954 TI - Abdominal ultrasonography following laparoscopic cholecystectomy: a prospective study. AB - Laparoscopic cholecystectomy has gained widespread acceptance as the operation of choice for symptomatic gall-stones. We prospectively performed ultrasonography on 100 consecutive patients after laparoscopic cholecystectomy to determine the effect of this procedure on common bile duct diameter. This study also examines the incidence and clinical significance of intra-abdominal fluid collections after laparoscopic cholecystectomy. Our results show that 24% of patients had dilatation of the common duct (greater than 6 mm) when scanned 48 h post operatively. The incidence of dilated common ducts fell to 9% when the patients were scanned 1 month later. This transient dilatation of the common duct, occurring post-operatively, has not been previously described. Intra-abdominal fluid collections were demonstrated in 10% of our patients but were clinically significant in only 1%. This study suggests that routine ultrasonography has a low yield immediately after laparoscopic cholecystectomy. PMID- 8435955 TI - Focal echogenic lesions in the spleen in sickle cell disease. AB - Focal echogenic lesions in the spleen were observed in 11 patients aged 9-17 years with sickle cell disease. All lesions were spherical and could be single or multiple. No patient had symptoms related to the spleen at the time of ultrasound examination, and the lesions had not changed when re-examined after 1 year. Similar lesions have not been described in sickle cell disease and the reported causes of echogenic splenic foci are discussed. It is suggested that, when seen in sickle cell disease, these foci are likely to have a benign cause, and that further investigation, especially for malignant disease, is not necessary. PMID- 8435956 TI - The mucosal rosette: a peri-ampullary pseudotumour within a duodenal diverticulum. AB - Two cases are described in which a filling defect within a duodenal diverticulum was suggestive of a peri-ampullary neoplasm. In each case direct inspection showed no abnormality. It is suggested that the radiological findings are caused by prominent mucosal folds around the diverticular neck. PMID- 8435957 TI - Pneumo-omentum following perforated greater curvature gastric ulcer. PMID- 8435958 TI - Ultrasound appearances of the rete testis. AB - Improved technology enables better visualization of normal anatomical structures. The rete testis is now visible as an ill-defined echo-poor region at the testicular hilum, sometimes with arboriform projections into the parenchyma. In a retrospective review of 100 cases of non-inflamed testes, the rete testis was seen in 18%. The anatomy was confirmed by scanning post-mortem specimens in a waterbath, marking the echo-poor region and then studying the histology. The spectrum of ultrasound appearances of the normal rete testis is presented. The rete testis can be distinguished easily from pathology because the parenchyma remains otherwise homogeneous and normal in appearance. PMID- 8435959 TI - Side effects and patient acceptability of transrectal biopsy of the prostate. AB - The side effects and patient acceptability of 230 ultrasound guided prostatic needle biopsies performed by the transrectal route in an out-patient setting were reviewed retrospectively. Most of the side effects were transient and mild; one patient required hospitalization for urinary retention. Patient acceptability was good; over 70% of patients reported no significant pain from the biopsy procedure. PMID- 8435960 TI - A technique for magnetic resonance imaging of the temporomandibular joint. AB - T1-weighted Magnetic Resonance Imaging (MRI) of 72 temporomandibular joints (TMJs) of symptomatic patients and normal subjects was performed after they had been clinically classified. The images were then interpreted by two radiologists, blinded to the clinical classification. The technique of imaging used a head coil for bilateral imaging, allowing a 3-position study in under 1 h. Correlation between MRI and clinical classification at the level of normal vs abnormal was achieved in 61/72 joints, giving a sensitivity of 79% and a specificity of 91% for MRI relative to the clinical assessment. True coronal images were of no added value. The addition of supplemental gradient-echo images was helpful in 12/15 joints. Osseous condylar abnormalities were present in 15 joints, all of which had otherwise identifiable disc abnormalities. Diminished condylar translation was a useful indirect sign of non-reducing disc displacement. We conclude that MRI is a very useful and reliable technique in TMJ imaging. The technique described is applicable to any MR unit, without the need for dedicated coils. PMID- 8435961 TI - Case report: spontaneous thrombosis of a spinal dural AVM (Foix-Alajouanine syndrome)--magnetic resonance appearance. AB - We describe a patient with a classical presentation of a spinal dural arteriovenous malformation which probably underwent spontaneous thrombosis. This is known as the Foix-Alajouanine syndrome. The diagnosis was not made in this patient until after cord infarction had occurred. The clinical and radiological features of spinal vascular malformations are reviewed because prompt treatment may halt or even reverse their neurological manifestations. PMID- 8435963 TI - Case report: rhabdomyolysis following grand mal seizures presenting as a delayed and increasingly dense nephrogram. AB - Rhabdomyolysis as a result of major trauma is a well recognized cause of acute renal failure. Non-traumatic rhabdomyolysis causing transient renal impairment may occur following generalized convulsions. We present a case in which rhabdomyolysis following epilepsy was first indicated at urography by a delayed and increasingly dense persistent nephrogram. PMID- 8435962 TI - Case report: MRI demonstration of pontine and thalamic myelinolysis in a normonatremic alcoholic. PMID- 8435964 TI - Case report: prolapse of an ampullary tumour beyond the duodeno-jejunal flexure. AB - We report unusual barium, computed tomographic (CT) and ultrasound appearances of a polypoid ampullary tumour which prolapsed beyond the duodeno-jejunal (DJ) flexure. The extensive mucosal prolapse gave rise to radiological signs suggestive of an intussusception. PMID- 8435965 TI - Patient monitoring in radiology. PMID- 8435966 TI - Sonographically guided coeliac plexus block. PMID- 8435967 TI - Transjugular intrahepatic portosystemic stent shunt: which metal stent? PMID- 8435968 TI - Foetal medicine and ultrasonography: a genetic perspective. PMID- 8435969 TI - Stereotactic localization mammography: interpreting the check film. PMID- 8435970 TI - Pregnancy and work in diagnostic imaging. PMID- 8435971 TI - Lower limb colour flow imaging: a comparison with ankle: brachial measurements and angiography. AB - Peripheral lower limb vascular disease represents a substantial health problem. Arteriography is currently the 'gold standard' imaging modality. However, much effort is presently being channeled towards alternative non-invasive techniques. To date, this involves mainly the interpretation of ankle: brachial pressure indices and segmental pressure measurements. A prospective pilot study of 20 patients (40 limbs) comparing these two techniques with colour Doppler ultrasound was carried out. Although ankle: brachial indices could accurately predict disease (sensitivity 100%, accuracy 92.5%), it failed to localize it; neither a high thigh: brachial index nor segmental drop could localize disease to the iliac (accuracy 70%) or femoro-popliteal (accuracy 55%) vessels respectively. Colour Doppler ultrasound correctly differentiated iliac from femoro-popliteal disease. It had an overall diagnostic accuracy of 90% in the femoral and popliteal vessels for both occlusion and stenosis and diagnosed 10 of 11 iliac lesions. Colour Doppler ultrasound has many advantages over pressure measurements in that it can both diagnose and localize arterial lesions accurately. We feel that using both techniques prior to angiography can accurately separate patients into either a surgical or angioplasty group. This may help utilize angiographic resources and radiologists' time more efficiently as well as reducing radiation dose to both patients and staff. PMID- 8435972 TI - Iodixanol in femoral arteriography (phase III): a comparative double-blind parallel trial between iodixanol and iopromide. AB - Iodixanol is a new non-ionic, dimeric contrast medium (CM) which is formulated to be isotonic with blood in all clinically relevant concentrations. This is a report of a parallel, double-blind study comparing the safety and efficacy of iodixanol with iopromide (Ultravist) in aortofemoral arteriography. One hundred consecutive, eligible patients scheduled to undergo peripheral arteriography were entered into the study and randomly allocated to receive one or other CM. Radiographic quality, discomfort, adverse events, femoral blood flow and renal function were examined. Ninety-five patients were successfully included in the study. Radiographic quality (efficacy) was found to be similar in both groups. Three patients (6%) in the iodixanol group and five patients (11%) in the iopromide group reported adverse events. In this respect there was no statistically significant difference between the two groups (P = 0.48), and all adverse events were mild and transient. Forty-six (97%) patients in the iodixanol group and 45 (100%) patients in the iopromide group experienced a sensation of warmth (discomfort) in connection with one or more of the injections. There was no statistically significant difference in the frequency of discomfort in the two groups. However, the intensity of warmth was significantly milder following iodixanol than after iopromide (P = 0.003, two-sided Mantel-Haenszel test). The mean percentage increase in femoral blood flow was found to be less with iodixanol (43.4%) than with iopromide (96.3%) (P < 0.05, Student's t-test). Renal function was affected slightly after administration of both CM. Serum creatinine and creatinine clearance were affected more by iodixanol than by iopromide, while the excretion of tubular enzymes was more affected by iopromide. In conclusion, this comparison between iodixanol and iopromide showed both contrast media to be safe, effective and well tolerated and the only major difference between them was in their effect on femoral blood flow. PMID- 8435973 TI - Cardiovascular changes during hypoglycaemia. PMID- 8435974 TI - A model approach for calculating the net capillary filtration rate during venous occlusion. AB - The venous occlusion method is commonly used to measure the net capillary filtration rate, calculated from the slope of the increasing volume curve of the limb at a given time. However, this technique does not take variation in the rate of venous filling into account. In the present study, a model of sum of two cumulative exponential functions was developed to describe the venous filling phase and the increase in interstitial fluid volume due to the net capillary filtration rate. The model was tested on 15 normal subjects and eight patients with post-thrombotic venous insufficiency. The cumulative exponential model gave a good description of the changes in volume that occur during venous occlusion. The model also enabled determination of the net CFR at the same phase of the maximal venous capacity. PMID- 8435975 TI - Variability of the computerized single-breath nitrogen washout test in healthy adults. Results from a field survey in a French rural area. AB - Within-subject (difference between paired tests, or coefficient of variation [c. var.] of three consecutive measurements) and between-subjects (standard deviation of the mean group) variability were assessed for the variables derived from the single-breath nitrogen (SBN2) test in a group of healthy, asymptomatic subjects (n = 289) aged 20-64 years, from a rural area in North-East France. Duplicate measurements in 99 subjects showed excellent agreement between the two attempts (correlation coefficients between 0.94 and 0.98) for static lung volumes and the alveolar N2 slope (PIII); closing volumes (CV) were more variable (r = 0.77 for absolute value, 0.79 for % VC) while closing capacities (CC) were in intermediate position (r = 0.86 for absolute value, and 0.88 for % TLC). The variability of three consecutive measures in 190 subjects showed the coefficients of variation to be low for static volumes and closing capacity (2.4-7.4%) and higher for PIII (15.1%) and CV or CV/VC (18.2 and 17.8%). The analysis of variance did not detect significant differences between the three sets of measurements, with the exception of a progressive increase of vital capacity (VC), and decrease in residual volume (RV) from test 1 to test 3, the total lung capacity being the same. Variability was uninfluenced by age or sex, except a higher c. var. for female VC as compared to males (2.8 vs. 2.2%, P = 0.02) and a higher variability of TLC (2.9 vs. 2.3%, P = 0.03) and VC (2.8 vs. 1.9%, P = 0.003) in people older than 40 years as opposed to those younger than 40 years. PMID- 8435976 TI - Attenuated Valsalva heart rate response in subjects with smoking history: possible role of autonomic dysfunction. AB - The effects of smoking habits on autonomic cardiovascular heart rate reflexes were studied in 143 healthy subjects by using the Valsalva manoeuvre and deep breathing tests. Smoking seemed to cause attenuation of the Valsalva heart rate response. This attenuation was present also after adjustment for possible confounding factors including alcohol consumption. Our findings show that in subjects with smoking history there may occur dysfunction in some part of the autonomic reflex arch mediating the Valsalva heart rate response. PMID- 8435977 TI - Oesophageal dysfunction in familial amyloidosis with polyneuropathy. AB - Sixteen patients with familial amyloidosis and polyneuropathy (FAP) and 14 health subjects underwent oesophageal manometry. Six of the patients had a severe oesophageal dysmotility with almost completely abolished propulsive pressure waves on swallowing in the lower 2/3 of the oesophagus. Ten patients had moderate dysfunction with reduced propulsive pressure wave amplitudes. Neostigmine increased the pressure wave amplitudes in healthy subjects but less so in the FAP patients. Scopolamine (Scopyl)-terbutaline (Bricanyl) almost abolished the propulsive pressure waves in healthy subjects and all patients in the lower 2/3 of the esophagus. Oesophageal distensibility, tested by inflating a rubber balloon in the oesophagus, was similar in FAP patients and healthy subjects. Thus, it is unlikely that amyloid deposits in the mucosal wall increased the oesophageal stiffness. An autonomic, predominantly vagal, denervation probably explains the disturbed function. PMID- 8435978 TI - Heart-rate variation: what are we measuring? AB - Many methods have been proposed during the last two decades for the assessment of autonomic nervous system function by quantification of the heart-rate variation (HRV). Relatively little has been written about the HRV in relation to physiological models of the heart-rate regulation. The integral pulse frequency model (IPFM) is a simple model that describes the genesis of heartbeats under the influence of the autonomic nervous system. By comparing simulated HRV data generated with the IPFM model with data from healthy volunteers we found similarities indicating that the model accurately reflects real data. Furthermore, we found a considerable difference between HRV measurements based on beat-by-beat heart-rate and measurements based on the heartbeat interval. Our results suggest that the commonly used electrocardiographic RR interval representation of heart-rate variation might possess an inherent nonlinear, mean heart-rate-dependent property indicating that analysis directly based on RR intervals can give biased results with respect to the underlying autonomic activity. The conclusions embrace all measurements of variation that are directly based on RR intervals including simple indices as well as higher-level quantification such as spectral analysis. PMID- 8435979 TI - High anaerobic energy release during submaximal arm exercise. AB - The anaerobic energy release during submaximal arm (AE) and leg exercise (LE) has been estimated from O2 deficit measured at the onset of exercise. Eight male subjects were studied during 8-10 min of arm or leg cycling at the same relative workload (53% of the peak exercise-induced increase in pulmonary oxygen uptake, VO2). The workloads were 78 +/- 4 W during AE and 173 +/- 11 W during LE and VO2 was 1.51 +/- 0.06 1 min-1 for AE and 2.33 +/- 0.15 1 min-1 for LE. The half-time of the VO2 on-response was considerably longer (P < 0.01) during AE (62 +/- 9 s) than during LE (33 +/- 4 s) and the peak blood lactate concentration was higher (P < 0.05) during AE (4.8 +/- 0.5 mmol.l-1) than during LE (3.5 +/- 0.4 mmol.l 1). Oxygen deficit was 1.64 +/- 0.16 and 1.78 +/- 0.16 1 for AE and LE respectively. Oxygen deficit was higher during AE than during LE when related to absolute workload (P < 0.01), or to VO2 at steady state (P < 0.001) or to limb volume (P < 0.001). The proportion of the total energy demand covered by anaerobic energy release at the onset of exercise (0-8 min) was about 54% higher (P < 0.01) during AE than during LE. It is concluded that the energy release to a greater extend is covered by anaerobic processes during AE than during LE. PMID- 8435980 TI - Accuracy and repeatability of a pocket turbine spirometer: comparison with a rolling seal flow-volume spirometer. AB - The accuracy and repeatability of a recently introduced pocket spirometer (Micro Spirometer; Micro Medical Instruments Ltd, Rochester, UK) was evaluated. FEV1 and FVC values obtained with this instrument were compared with those measured with a rolling-seal flow-volume spirometer (CPI 220 with microcomputer) in 31 patients and 11 healthy volunteers. In the whole material, expressed as mean +/- SD, the pocket spirometer recorded 0.44 +/- 0.23 l (13 +/- 7%) smaller values for FEV1 (P < 0.001) and 0.64 +/- 0.48 l (15 +/- 11%) smaller values for FVC (P < 0.001) than the rolling-seal spirometer. The short-term repeatability of the measurements expressed as the coefficient of variation of repeated measurements using the pocket spirometer was 2.2% for FEV1 and 2.3% for FVC in a series of 10 healthy subjects and 10 patients with COPD. It is concluded that the underestimation of FEV1 and FVC of the pocket spirometer was too large and inconsistent for the device to be used interchangeably with conventional spirometers. However, the repeatability of the measurements with the pocket spirometer is close to that reported previously for flow-volume spirometry. Thus the pocket spirometer may be suitable in assessing acute changes of spirometric indices e.g. during provocation tests or during patient follow-up in asthma. PMID- 8435981 TI - Venous plasma noradrenaline increases with age: correlation to total blood volume and long-term smoking habits. AB - Venous plasma noradrenaline (NA), cardiac index, total blood volume, and other haemodynamic parameters were measured in 12 young (median age of 29, range 21-37 years) and 10 elderly (median age of 68, range 55-85 years) healthy male subjects in the resting supine and sitting positions. Cardiac index was equal in the two groups and did not correlate to plasma NA. Plasma NA was significantly elevated in the elderly subjects in the sitting position (2.47 +/- 0.28 vs. 1.80 +/- 0.13 nmol l-1, P = 0.038). Elevated plasma NA levels were confined to elderly long term smokers. Sitting plasma NA was significantly correlated to total blood volume corrected for body weight, r = -0.720, P = 0.0002, but with no difference in blood volume between smokers and non-smokers. It is concluded, that long-term smoking may result in elevated plasma NA levels seen in elderly subjects. It is suggested, that this is a compensatory mechanism to vascular dilation induced by chronic smoking. PMID- 8435982 TI - Altered structural and dynamic properties of blood cell membranes in diabetes mellitus. PMID- 8435983 TI - Increased red cell aggregation in diabetes mellitus: association with cardiovascular risk factors. AB - Red cell aggregation may be higher in diabetic patients and may predispose to cardiovascular disease. Red cell aggregation was measured by a simple photometric method in 122 diabetic patients and 100 matched control subjects, to determine its relationship to cardiovascular risk factors. Red cell aggregation was significantly increased in both Type 1 (4.3 +/- 1.3 vs 3.4 +/- 1.2, p < 0.002) and Type 2 diabetic patients (5.5 +/- 1.5 vs 3.2 +/- 1.3, p < 0.0001). In all diabetic patients aggregation correlated with triglycerides, VLDL, and inversely with HDL and in Type 2 diabetic patients also with body mass index, hypertension, and inversely with duration of diabetes. On multiple regression analysis, triglycerides and body mass index showed an independent association with red cell aggregation and in Type 2 diabetic patients smoking was also associated with increased red cell aggregation. It is concluded that increased red cell aggregation may be one mechanism by which some cardiovascular risk factors could promote cardiovascular disease in diabetes. PMID- 8435984 TI - Insulin therapy in type 2 diabetic subjects suppresses plasminogen activator inhibitor (PAI-1) activity and proinsulin-like molecules independently of glycaemic control. AB - Eleven Type 2 diabetic subjects (10 male 1 female: age 56.2 +/- 9.7 (SD) yr) were treated in random order either with insulin or with sulphonylureas for 8 weeks each, without attempting to alter glycaemic control between the two treatment periods. Insulin treatment was associated with suppression of endogenous insulin secretion (fasting C-peptide levels -35.0 +/- 24.2%; p = 0.006), and of intact proinsulin (-43.1 +/- 36.8%; p = 0.03) and 32,33 split proinsulin -20.1 +/- 27.0%; p = 0.03). Activity of plasminogen activator inhibitor (PAI-1), a fast acting inhibitor of fibrinolysis, decreased significantly (-14.3% +/- 27.5%; p = 0.02) but no changes occurred in concentration of lipoproteins or apoproteins between therapies. Changes in concentrations of 32,33 split and intact proinsulin were closely and significantly related (rs = 0.83; p < 0.001) to each other but not with changes in concentrations of C-peptide (intact proinsulin rs = -0.41; p = 0.11) and 32,33 split proinsulin rs = -0.27; (p = 0.21). Percentage changes in intact proinsulin concentrations were positively correlated with those in PAI-1 (rs = 0.51; p = 0.05). There was, however a paradoxical negative relationship between changes in C-peptide concentrations and those of PAI-1 (rs = -0.73; p = 0.006). These preliminary observations suggest that insulin treatment in Type 2 diabetic subjects without any changes in glycaemic control is associated with a reduced activity of PAI-1, but is without effect on any other cardiovascular risk factors. Concentrations of insulin precursor molecules may play a role in determining fibrinolytic activity. PMID- 8435985 TI - Association of erythrocyte aldose reductase activity with diabetic complications in type 1 diabetes mellitus. AB - Erythrocyte aldose reductase was isolated and its activity measured in 72 Type 1 (insulin dependent) diabetic patients and 21 age and sex matched non-diabetic subjects. The diabetic patients were categorized into two groups in terms of presence (n = 29) or absence (n = 43) of severe diabetic complications. Age, sex, duration of diabetes and HbA1c levels were matched between the diabetic groups. Erythrocyte aldose reductase (mean +/- SEM) was increased in patients with Type 1 diabetes compared to the non-diabetic subjects (7.22 +/- 0.24 vs 5.66 +/- 0.19 Ul erythrocytes-1, < 0.0001). There was a four-fold variation in its activity among the diabetic patients (3.38-12.23 Ul-erythrocytes-1). The enzyme activity was significantly higher in patients with complications than those without (8.17 +/- 0.39 vs 6.58 +/- 0.26 Ul-erythrocytes-1, p < 0.002). When the patients were stratified by duration of the disease, the enzyme activity was highest in patients who had developed complications with a duration of less than 20 years and lowest in those without complications for 20 years or longer (8.54 +/- 0.48 vs 6.46 +/- p +/- 0.33 Ul-erythrocytes-1, p < 0.002). Patients who had an aldose reductase activity greater than the mean +/- 2SD of that seen in non-diabetic controls were four times more likely to have diabetic complications than those whose enzyme activity fell within 2SD of non-diabetic individuals (p < 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8435986 TI - Acute effects of local hyperglycaemia on peripheral blood flow in man. AB - To determine whether local hyperglycaemia affects peripheral blood flow in man, total forearm and skin microcirculatory blood flow were studied in healthy subjects before, during, and after a 1-h infusion of different concentrations of glucose or mannitol in the brachial artery. Mild or high forearm hyperglycaemia induced by 5% glucose infusion (approximately 10 mmol l-1 and approximately 18 mol l-1, respectively) did not induce any changes in forearm muscle or skin blood flow. However, mild forearm hyperglycaemia (approximately 8 mmol l-1), induced by 20% glucose infusion, acutely increased forearm blood flow, decreased forearm vascular resistance, but did not change skin blood flow. Twenty percent Mannitol infusion, as an osmotic control, did not result in any changes. We conclude that intra-arterial administration of 5% glucose does not acutely affect peripheral blood flow. The glucose-related effect induced by 20% infusion is probably due to marked hyperglycaemia at the catheter tip. PMID- 8435987 TI - Hypersecretion of truncated glucagon-like peptide-1 and gastric inhibitory polypeptide in obese patients. AB - Postprandial insulin secretion is modulated by both neural and humoral gastrointestinal insulinotropic factors in addition to the absorbed nutrient. To investigate the involvement of the potent insulinotropic hormones gastric inhibitory polypeptide (GIP) and truncated glucagon-like peptide-1 (tGLP-1) in the postprandial hyperinsulinaemia of obesity, we examined the changes in plasma levels of GIP and tGLP-1 by an oral glucose tolerance test (OGTT) in nine normal subjects (controls), nine obese subjects without glucose intolerance (Group A), and six obese mild diabetic patients (Group B). Following the OGTT, plasma GIP levels in Group B were increased more markedly than those in the other two groups. Plasma levels of tGLP-1 were estimated by the difference between the values measured with the N-terminal directed antiserum (GLP-1NT) and those with the C-terminal directed antiserum (GLP-1 CT). Plasma levels of GLP-1 NT were increased in Group B, but decreased in the other two groups. Plasma GLP-1 CT levels were increased in all groups with the highest response in Group B. These results suggest that the combined augmentation of plasma GIP and tGLP-1 responses were involved in the delayed and considerable increases in plasma insulin after glucose ingestion in obese diabetic patients. Since tGLP-1 is suppressed in the hyperglycaemic hyperinsulinaemic state in normal subjects, the augmented tGLP-1 response appears to be characteristic of obese Type 2 diabetes. PMID- 8435988 TI - Changes in glucose disposal and cellular insulin binding in obese black Southern African patients with type 2 diabetes mellitus before and after sulphonylurea therapy. AB - Peripheral insulin action and cellular insulin binding were studied in 10 newly detected, obese, black, Southern African women with Type 2 diabetes mellitus before and after mid-term oral sulphonylurea therapy and in five obese, non diabetic controls. Glucose disposal (assessed by the euglycaemic insulin clamp technique) was significantly reduced in diabetic patients compared to control subjects (4.4 +/- 0.5 vs 6.4 +/- 0.5 mg kg-1 min-1, p < 0.05), and increased after 1 and 3 months of sulphonylurea therapy to 6.8 +/- 0.6 mg kg-1 min-1 (p = 0.01) and 6.3 +/- 0.7 mg kg-1 min-1 (p = 0.04), respectively. The major change in the binding kinetics of insulin to peripheral monocytes was an increase in the mean receptor concentration in the diabetic patients which was significant after 3 months of therapy (0.2 +/- 0.08 to 0.6 +/- 0.01 nM, p = 0.05). The basal plasma C-peptide concentration was significantly lower in the diabetic patients than in the controls and remained so following sulphonylurea therapy, despite significant reductions in fasting glucose and HbA1 concentrations. We conclude that newly diagnosed, obese, black Southern Africans with Type 2 diabetes showed diminished peripheral glucose disposal which increased following sulphonylurea therapy. This was accompanied by an increase in insulin receptor concentration but not with changes in basal insulin secretion. PMID- 8435989 TI - Is serum anhydroglucitol an alternative to the oral glucose tolerance test for diabetes screening? The Mauritius Noncommunicable Diseases Study Group. AB - The oral glucose tolerance test is inconvenient for diabetes screening. In clinical studies a reduced serum anhydroglucitol level has proved to be a sensitive and specific test for diabetes. A new minicolumn enzymatic method which is simple and robust makes use in population screening feasible. The aim of our study was to assess the usefulness of a single measurement of anhydroglucitol to screen for diabetes and impaired glucose tolerance. Assays were performed on samples taken from 227 Mauritian Chinese subjects at the time of glucose tolerance testing. Subjects had normal glucose tolerance (n = 82), impaired glucose tolerance (n = 76), newly diagnosed diabetes (n = 38), and known diabetes (n = 31). Anhydroglucitol concentrations (mean +/- SD) were similar for normal and impaired glucose tolerance subjects (23.7 +/- 8.2 vs 23.4 +/- 8.6 mg l-1). Although the differences between normal and newly diagnosed diabetes (15.0 +/- 11.0 mg l-1) and known diabetic subjects (11.8 +/- 10.6 mg l-1) were significant (p < 0.001), diagnostic sensitivity and specificity were poor. We conclude that measurement of serum anhydroglucitol is not suitable for screening for the diagnoses of impaired glucose tolerance and diabetes. PMID- 8435990 TI - Does ethanol cause hypoglycaemia in overnight fasted patients with type 1 diabetes? AB - Drinking ethanol is widely believed to predispose to hypoglycaemia in patients with Type 1 diabetes, the suggested mechanism being suppression of hepatic gluconeogenesis. The hypoglycaemic effect of ethanol was investigated by measuring steady-state glucose infusion rate during a hypoinsulinaemic (mean plasma insulin 14 +/- 1.3 (SEM) mU l-1), euglycaemic (blood glucose 5 mmol l-1) clamp. Nine patients with Type 1 diabetes fasted overnight and then had, in single-blind fashion, ethanol 0.5 g kg-1 by intravenous bolus followed by 0.25 g kg-1 h-1 or matched volumes of saline. After 1 h of ethanol or saline, all infusions were stopped and blood glucose monitored for a further 90 min. A 60-min ethanol infusion leading to a steady-state blood concentration of 26.2 +/- 1.4 mmol l-1 (120.7 mg %) did not alter the glucose infusion rate needed to maintain euglycaemia (1.22 +/- 0.12 mg kg-1 min-1 before and 1.23 +/- 0.12 during ethanol infusion), the initial rate of fall of blood glucose (ethanol 0.039 mmol l-1 min 1 vs control (0.033), the lowest blood glucose (4.43 mmol l-1 vs 4.31), or the rate of blood glucose recovery (ethanol 0.050 mmol l-1 min-1 vs control 0.054). We conclude that a moderate amount of ethanol, administered intravenously under controlled conditions, does not lead to hypoglycaemia in patients with Type 1 diabetes who have fasted overnight. PMID- 8435991 TI - Effect of metabolic control on autonomic function in obese patients with newly diagnosed type 2 diabetes. AB - To evaluate the effect of diet therapy and physical exercise on autonomic nervous function in newly diagnosed Type 2 diabetes, we followed 83 middle-aged obese patients (48 men, 35 women) for a 15-month period. After a 3-month basic education programme the patients were randomized to one of two groups for comparison of standard treatment given by community health centres (conventionally treated group) and intensive dietary and exercise education (intervention group). Autonomic function was assessed by heart rate variability during deep breathing (expiration/inspiration ratio, E/I), and by systolic blood pressure response to standing up. The intensively treated women (n = 18) had the best blood glucose throughout the study, and this was the only group to show an improvement in E/I ratio (1.19 +/- 0.03 vs 1.30 +/- 0.05, mean +/- SEM, p < 0.05). None of the groups showed any significant change in systolic blood pressure response to standing up. For further analyses, the original groups were combined and thereafter divided into those with declining fasting blood glucose during the intervention phase (n = 39) and into those with no change or increase in blood glucose level (n = 44). The group with improving blood glucose level showed an increase in E/I ratio (1.22 +/- 0.02 vs 1.28 +/- 0.03, p < 0.01) while in the other group E/I ratio remained unchanged (1.21 +/- 0.02 vs 1.20 +/- 0.02). The difference in E/I ratio between these two groups was significant at 15 months (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8435992 TI - Self-care behaviour and blood glucose control in young adults with type 1 diabetes mellitus. AB - Self-care behaviour, knowledge about diabetes, and blood glucose control were studied in 113 young adults with Type 1 diabetes using a semi-structured interview, self-report questionnaires, and a biochemical measure (glycated haemoglobin). The majority of subjects followed their prescribed regimen reasonably accurately, but individuals followed different aspects of the regimen to different degrees. Subjects were more concerned with the avoidance of hypoglycaemia than with attainment of 'tight' blood glucose control. The blood glucose test level at which subjects took remedial action was the best single predictor of symptomatic control. Frequency of nocturnal polyuria appeared to be a reliable indicator of impaired metabolic control. Insulin omission or dose reduction for the purpose of body weight reduction was common among women, who also had worse blood glucose control than men. Elevated glycated haemoglobin levels were associated with higher alcohol consumption in men. Theoretical knowledge about diabetes management was only weakly associated with self-care behaviour and blood glucose control in this population. The blood glucose test result at which subjects take remedial action appears to be the most appropriate behavioural target for intervention to improve control in such subjects. PMID- 8435993 TI - Cultural and religious influences in diabetes care in Great Britain. AB - Type 2 diabetes is four times more common in people originating from the Indian subcontinent (Asians) than in white English Caucasians. British Asians with diabetes have been shown to have poorer blood glucose control, awareness of diabetes management, and knowledge of complications. This review examines some of the dietary customs that can affect glucose control, problems with communication and diabetic education, and a brief description of health beliefs commonly held by Asian patients that may help the physician understand why some patients appear to show poor compliance with accepted Western medicine. Patients must always be approached as individuals with their own unique needs within the context of their cultural backgrounds. PMID- 8435994 TI - Sharing the care of diabetic patients between hospital and general practitioners: does it work? AB - A randomized controlled trial was conducted to compare three forms of diabetes follow-up: (1) general practitioner care, (2) a system of care shared between the general practitioner (GP) and clinic and (3) conventional clinic care. Two hundred and six diabetic patients without significant diabetes-related or other medical complications were randomized to one of these follow-up systems. Metabolic control and blood pressure improved significantly and equally in all three groups (p < 0.05). The shared care group performed as well as or better than either of the other two groups in all other outcome measures. In particular, final attendance rates were 72% for shared care compared with only 35% for GP care and 53% for clinic care. Data collection rates for shared care were comparable with the clinic group for random blood glucose (88.9% vs 95.1%), weight (93.5% vs 98.3%), and blood pressure (94.8% vs 92.7%). Only in the case of glycosylated haemoglobin did shared care have poorer data collection (66.0% vs 98.4%). In all these parameters, except blood pressure, shared care out-performed the GP group. We conclude that with adequate support from and communication with hospital-based diabetes services, GPs are capable of providing care appropriate to the needs of uncomplicated diabetic patients. PMID- 8435995 TI - Evidence for an increase in the prevalence of known diabetes in a sample of an urban population in Greece. AB - It is accepted that the prevalence of known diabetes mellitus has increased in some countries, although the available data are incomplete and sometimes anecdotal. In 1974 a sample of the urban population (n = 21,410) in a suburb of Athens (Greece) was evaluated for the prevalence of known diabetes mellitus. The study was repeated 17 years later in the same area under the same conditions and methodology on 12,836 randomly selected inhabitants (both sexes, all ages). Visiting nurses contacted the inhabitants at home and filled in a questionnaire. The results show a clear increase in diabetes prevalence of the population as a whole (standardized rates: 1974: 2.4% (95% confidence intervals 2.2-2.6%) 1990: 3.1 (2.8-3.4%)). Standardization was done on the basis of data obtained from the same census. The changes were statistically significant in the 50-59, 60-69, and 70-79 age groups (1974: 5.87, 10.98, and 11.41%; 1990: 7.70, 13.68, and 19.52%, respectively). Thus, the prevalence of known diabetes mellitus has considerably increased during the last 17 years in a sample of urban Greek population. PMID- 8435996 TI - Provision of biochemical tests for diabetes clinics: findings of a national survey. PMID- 8435997 TI - The safety and efficacy issues of progestin-only oral contraceptives--an epidemiologic perspective. AB - Progestogen-only oral contraceptives (POCs) are generally considered a good contraceptive choice for brestfeeding women and for women who want to use an oral form of contraception, but are not suited for, or cannot tolerate the side effects of, estrogen-containing preparations. However, a number of POCs' safety, efficacy and other related issues remain to be addressed. This paper reviews recent literature and evaluates these issues from an epidemiologic perspective. The small number of users imposes severe limitations in designing epidemiologic studies to address POCs' long-term safety issues, but available information suggests POCs are at least as safe as, if not safer than, COCs. Compared to COCs, POCs are more likely to cause menstrual disturbances which, in turn, could affect their acceptability and lead to poor compliance and hence higher pregnancy rates. POCs' efficacy has been estimated to be between 1.4 and 4.3 pregnancies per 100 woman-years of use. Lower pregnancy rates approaching those of COCs have been reported in centers with good counseling. POCs' benefits outweigh their risks. However, more studies are needed to further address POCs' safety and efficacy issues. PMID- 8435998 TI - Sterilization of dogs with intra-epididymal injection of zinc arginine. AB - Condoms and vasectomy are the only fertility control methods available to males. Fifty million surgical vasectomies have been performed worldwide. In spite of improvements in the surgical techniques, the widespread use of vasectomy is limited due mainly to fear of genital operation. Chemical sterilization offers a promising new approach as an alternative to surgery. Fifteen sexually mature, mixed breed, male dogs, 2-3 1/2 years of age and weighing 22 +/- 1.8 kg, were divided into two groups. Five control placebo animals were injected with 0.5 ml of saline into the cauda epididymis, and ten treated animals were injected with 0.5 ml of 50 mg of zinc arginine into the cauda epididymis. Semen analysis performed before injection showed no significant difference between control placebo and treated groups. The control placebo animals exhibited a significant reduction in sperm motility one month after injection, which returned to normal within two months, and no change in semen volume, sperm abnormalities, or sperm concentration analyzed monthly for twelve months. The zinc arginine-treated animals achieved azoospermia ninety days after injection. The dogs were sacrificed one year after injection. There was no significant reduction of reproductive organ weights of the treated group as compared to the control placebo group. Although histological examination of the testes revealed normal seminiferous tubules, there was atrophy of the rete testes of the zinc arginine treated group and, thus, increase in connective tissue. Histological examination of epididymides of the zinc arginine-treated group indicated that none of the cells in the head, body, and tail of the epididymis and ductus deferens contained sperm; 90% of the coils were empty and 10% contained amorphous pink cell debris; the coils decreased in diameter and were lined by cuboidal to columnar epithelium; no granuloma was observed. There was no significant change in serum testosterone level of control placebo and treated groups. These results offer the possibility of a new method of permanent sterilization instead of surgery. Zinc is considered to be nonmutagenic, noncarcinogenic, and nonteratogenic. PMID- 8435999 TI - A multicenter clinical trial of a progestin-only oral contraceptive in lactating women. AB - A non-comparative study of a progestin-only oral contraceptive (POC) containing 75 micrograms norgestrel was conducted at 22 sites in 14 countries. This study was designed to evaluate safety, contraceptive efficacy, and the overall acceptability of a POC in breastfeeding women. A total of 4,088 women entered the study over a three-year period and 29,399 woman-months of experience was gathered. Women had follow-up visits at 2, 6, and 11 months after admission. Headaches and vaginal discharge were the medical complaints most commonly reported by women, both prior to and after admission. Menstrual problems were reported by 59% of the women after admission. Of the 3,714 women who returned for at least one follow-up visit, 1,101 (29.6%) discontinued through month 11. The 11 month total discontinuation percentage, including those lost to follow-up (25.3%) was 51.6%. The most common reason given for discontinuation was a woman's desire for a change in contraceptive method. Only 4.9% discontinued pill use for menstrual problems, a percentage far below those generally reported for POCs. Twenty-nine unintended pregnancies occurred through 11 months giving a gross cumulative life table rate of 1.2 per 100 women (Pearl Index = 1.4). The POC appears to be a safe, effective and acceptable contraceptive option for postpartum breastfeeding women. PMID- 8436000 TI - Four-year experience in a randomized study of the Gyne T 380 Slimline and the Standard Gyne T 380 intrauterine copper devices. AB - Performance of the Slimline and Standard models of the Gyne T 380 were measured through four years in a comparative study initially involving 996 women, seventy percent of whom were randomized to the Slimline device. Cumulative pregnancy rates of Slimline users were 0.3 +/- 0.2 per 100 both at three and at four years, as compared with rates of 1.5 +/- 0.9 and 3.8 +/- 1.7 at the same intervals for users of the Standard model (P > .05). The four-year explusion rate of the Slimline, 8.6 +/- 1.3 per 100, was significantly higher than the comparable rate of the Standard model, 4.4 +/- 1.6 (P < .05). The two Gyne T* models did not differ in continuation rates. First time IUD users, however, had substantially lower continuation rates than did former users (P < .001), in consequence of their relative youth and desire to have additional children. Other performance measures did not differ importantly by device. PMID- 8436001 TI - A clinical comparison of two triphasic oral contraceptives with levonorgestrel or norethindrone: a prospective, randomized, single-blind study. AB - Menstrual bleeding patterns were investigated in young women taking either a levonorgestrel triphasic, Triquilar, or a norethindrone triphasic, Ortho 7/7/7, two commonly prescribed low-dose oral contraceptives. The levonorgestrel triphasic contains ethinyl estradiol (EE) 30 micrograms + levonorgestrel (LNG) 50 micrograms for the first six days, EE 40 micrograms + LNG 75 micrograms for the following five days, and EE 30 micrograms + LNG 125 micrograms for the last ten days. The norethindrone triphasic contains EE 35 micrograms + norethindrone (NET) 0.5 mg for the first seven days, EE 35 micrograms + NET 0.75 mg for the following seven days and EE 35 micrograms + NET 1.0 mg for the last seven days. Three hundred women from 16 to 25 years of age were randomized to the levonorgestrel triphasic (n = 150) or the norethindrone triphasic (n = 150) groups. Assessments were made from daily diary cards and from bimonthly investigator interviews over 6 pill cycles. The results showed a higher incidence of intermenstrual bleeding (breakthrough bleeding and/or spotting) in the norethindrone triphasic group (NET group) than in the levonorgestrel triphasic group (LNG group): 44.9% of patients (66/147) randomized to the LNG group reported intermenstrual bleeding one or more times during the study compared with 61.9% (91/147) randomized to the NET group (p = 0.0036). Furthermore, in subjects who did not miss any pills, the proportion of patients with intermenstrual bleeding in each cycle was significantly greater (p < 0.02, cycles 1-4, 6; p > 0.05, cycle 5) and was experienced for more days per cycle (p < 0.05, cycle 1) and for more cycles per patient (p < 0.05, 5 cycles) in the NET group compared with the LNG group. Intermenstrual bleeding was also less frequently observed in the LNG group than in the NET group in patients who missed pills (p < 0.05, cycles 3, 5 and 6). In addition, early withdrawal bleeding occurred more often in the NET group than in the LNG group (p < 0.05, cycles 1, 3 and 4). The incidence of amenorrhea was similar in both groups. These results demonstrate a significantly lower incidence of intermenstrual bleeding and therefore better cycle control with the levonorgestrel triphasic Triquilar, compared with the norethindrone triphasic Ortho 7/7/7. PMID- 8436002 TI - The effect of a biphasic desogestrel-containing oral contraceptive on carbohydrate metabolism and various hormonal parameters. AB - During 6 cycles of treatment of 19 women, the effect of a low-dose biphasic oral contraceptive containing 40 micrograms ethinylestradiol + 25 micrograms desogestrel (7 tablets) and 30 micrograms ethinylestradiol + 125 micrograms desogestrel (15 tablets) on various hormonal parameters and glucose metabolism was compared with the values of the pre- and post-treatment cycle. There was a profound reduction in gonadotropin secretion and ovarian steroid synthesis. The serum levels of testosterone were reduced by 35%, free testosterone by 55%, and DHEA-S by 30%. Cortisol increased by 100%, SHBG by 250%, and TBG by 60%, while FT3 and FT4 were only marginally influenced. Fasting levels of glucose and insulin did not change significantly, but the glucose load revealed a slight impairment of glucose tolerance. Three weeks after termination of pill intake, the various parameters returned to pretreatment levels, except for SHBG and TBG which were still elevated by 20 to 30%. The results demonstrate a marked preponderance of the effect of the estrogen component, a reliable inhibition of ovulation and very good cycle control during treatment with the biphasic formulation. PMID- 8436003 TI - Effect on lipid metabolism of a biphasic desogestrel-containing oral contraceptive: divergent changes in apolipoprotein B and E and transitory decrease in Lp(a) levels. AB - The effect of a low dose biphasic oral contraceptive containing 40 micrograms ethinylestradiol + 25 micrograms desogestrel (7 tablets) and 30 micrograms ethinylestradiol + 125 micrograms desogestrel (15 tablets) on lipid metabolism was investigated in 19 women during 6 cycles of treatment and compared to the values of the pre- and post-treatment cycle. During treatment, all components of HDL increased reversibly by 10 to 30%. The levels of total cholesterol (CH), LDL CH and IDL-CH rose only slightly, while those of total triglycerides (TG), VLDL TG and LDL-TG rose continuously by more than 100% until the 6th cycle. At the same time, plasma levels of VLDL-CH increased by 60% and of apolipoprotein B by 20%. Contrary to this, apolipoprotein E decreased by 25% during treatment, and Lp(a) was transitorily reduced during the 3rd cycle. After termination of intake, total CH, LDL-CH, IDL-CH and apolipoprotein B remained elevated, while total TG, VLDL-TG, VLDL-CH and LDL-TG decreased significantly, but were still elevated during the post-treatment cycle. The levels of apolipoprotein E returned to pre treatment values. The results indicate a marked preponderance of the effect of the estrogen component. The rise in TG and VLDL synthesis seems to be outweighed by an enhanced removal of apolipoprotein E-containing remnants which might offer protection from the development of atherosclerosis. PMID- 8436004 TI - Blood loss in termination of early pregnancy by vacuum aspiration and by combination of mifepristone and gemeprost. AB - Blood loss was measured in 17 subjects undergoing surgical termination of pregnancy and in 96 subjects undergoing medical termination of pregnancy with sequential mifepristone (200 mg, 400 mg, 600 mg) and 1 mg prostaglandin analogue gemeprost. The median blood loss were 53.2, 84.1, 99.9 and 101.4 ml, respectively. There was a statistically significant difference between the surgical and each of the medical termination group of subjects but there was no difference among the subgroups in the medical termination group. The pattern of bleeding was also similar, being heaviest on the day and the days shortly after prostaglandin administration. Majority of them (> 90%) experienced blood loss of < 300 ml and there was no significant drop in hemoglobin level during the 6-week follow-up period. A few women experienced heavy bleeding and, hence, strict supervision on medical termination of pregnancy is recommended. PMID- 8436005 TI - One year contraception with a single subdermal implant containing nomegestrol acetate (Uniplant). AB - One single silastic capsule containing nomegestrol acetate, Uniplant, was inserted subcutaneously in 100 women of reproductive age who desired to avoid conception. Insertions and removals of the capsules were made in the gluteal region following intracutaneous local anesthesia with 2% procaine. Eighty women completed one year of use. Eleven women bore the implant for 6-11 months. A total of 1,085 women-months were recorded. One pregnancy occurred, resulting in a Pearl Index of 1.1. Bleeding episodes similar to menstruation occurred in all women but the degree of regularity varied from subject to subject. Amenorrhea developed in the range of 14-18% during the first six months of use but declined to less than 10% during the last six months. Menorrhagia likewise was higher in the first six months (18% in the first month) but fell to less than 10% during the last six months. Spotting was 5% or less. Of the twenty women who did not complete one year of use, nine discontinued because they found other methods were either more practical or less revealing. Three discontinued because of bleeding irregularities, three desired to become pregnant, one became pregnant. Other complaints included dizziness, headache, increased blood pressure, loss of libido, painful breasts and nausea. Over half of the women indicated their desire to continue using the single implant as a contraceptive. PMID- 8436006 TI - A temperature dependent action of fluoride on aqueous outflow facility of the calf eye. AB - A number of investigators have studied the effect of metabolic inhibitors on the facility of aqueous outflow from the enucleated eye perfused eye at "room temperature". Some inhibitors such as iodoacetate and iodoacetamide increased the facility, others such as p-chloromercuri-benzoate decreased it. Most however, including sodium fluoride, were reported to have had no effect. We have found that 10 mM sodium fluoride had a very small effect on facility of aqueous outflow at room temperature (22 degrees C), but reduced the facility as much as 50% (average 30%) at 35 degrees C. The magnitude of the sodium fluoride effect did not appear to be dependent on calcium levels in the medium, but the presence of Ca2+ significantly prolonged its duration. Iodoacetamide and iodoacetate both increased facility at 35 degrees C in a manner similar to previous findings at room temperature except that at 8-10 mM, iodoacetate caused a 55% decrease; under these conditions, there was considerable release of tissue debris into the anterior chamber which probably blocked the TM. A number of other agents, such as 2,4-dinitrophenol, KCN, and 2-deoxyglucose were studied, but none produced any marked effect on facility. These results emphasize that temperature may profoundly modify the effect of metabolically active agents. The mechanism of the fluoride effect has not been determined but it is consistent with the action of F on the G protein associated with phospholipase C. PMID- 8436007 TI - Fractal analysis of the normal human retinal fluorescein angiogram. AB - The fractal dimension of the retinal vasculature and isolated venous and arterial trees down to a caliber of 40 microns was estimated in 23 routine fluorescein angiograms of normal retinas. Fractal dimension was determined with a method based on the box counting theorem. This method is less susceptible to the radial architecture of the retinal vascular tree than those previously reported (mass radius relation and density-density correlation function). Two scale ranges with different fractal dimension were consistently present. The estimated fractal dimensions showed no significant difference between isolated arterial and venous trees which is not supported by previous reports. This method was designed for simple application in a clinical setting. PMID- 8436008 TI - Properties of taurine transport in a human retinal pigment epithelial cell line. AB - The characteristics of taurine transport were studied in a human retinal pigment epithelial cell line (HRPE). Uptake of taurine into monolayer cultures of the HRPE cells was markedly stimulated by the presence of NaCl in the uptake medium whereas the uptake was negligible in its absence. This NaCl-dependent uptake was an active process as the cells were able to accumulate taurine against a concentration gradient. The uptake rate of taurine was found to be many-fold greater than that of gamma-aminobutyric acid (GABA). Unlabeled taurine and GABA competed with radiolabeled taurine for the uptake process, the former being more effective than the latter. However, uptake of radiolabeled GABA was not affected by unlabeled taurine and GABA. Substrate specificity studies revealed strong interaction of beta-amino acids with the transport system responsible for taurine uptake. alpha-Amino acids failed to inhibit taurine uptake. A specific anion requirement was observed for optimal activity of the taurine transport system and Cl- was the most supportive among several anions tested. Kinetic analyses showed that multiple Na+ and one Cl- were involved in transfer of one taurine molecule. The transport process consisted of a single saturable system with a Michaelis Menten constant of 2.0 +/- 0.1 microM. These results show that the HRPE cell line expresses a high-affinity taurine transport system. This is the first demonstration of the presence of the taurine transporter in the human retinal pigment epithelium and the HRPE cell line may provide a useful model system for future studies involving taurine transport in the retinal pigment epithelium. PMID- 8436009 TI - Diurnal variation in myeloid bodies of the chick retinal pigment epithelium. AB - Myeloid bodies (MBs) are distinct lamellar regions of the normally branched tubular smooth endoplasmic reticulum of retinal pigment epithelial (RPE) cells. These organelles are present in the retinas of many lower vertebrates. Previous investigations have reported a relationship between outer segment disk shedding and phagocytosis by the RPE, and the formation of MBs. The current morphometric study was undertaken to establish if a temporal relationship existed between MB occurrence and the phagocytosis of shed photoreceptor outer segment tips in the chick retina. We report on the occurrence of phagosomes, MBs, and for the first time, MB precursors (templates) in the RPE over a 24-hr diurnal cycle. Phagosome numbers were observed to be highest within 2 hr following lights on, and again following lights off, while MB precursors were most prevalent at two time points, immediately prior to the times for rod and cone outer segment shedding at lights on and lights off respectively. Traditional MBs of the small (0.06 to 0.239 microns2) and medium (0.24 to 0.99 microns2) variety increased both in size and number from 01:00 hr of a 24 hr time period, with smaller and fewer MBs being present late in the dark part of the diurnal cycle, and larger and more numerous MBs in the later part of the light portion and into the early part of the dark portion of the cycle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8436010 TI - Monensin enhances the cytotoxic effect of antitransferrin receptor immunotoxin on cultured RPE cells. AB - The effect of monensin on the cytotoxic effect of antitransferrin receptor immunotoxin (IT) was determined on cultured, human retinal pigment epithelial (hRPE) cells. Human RPE cells were treated with 0.1-10,000 ng/ml IT with and without 0.01-0.1 microM monensin, a lysosomotropic reagent that can influence IT activity. Monensin (0.01 microM) shortened the onset of cell kill with IT (10,000 ng/ml) from 48 to 24 hours (p = 0.0016). Although 0.01 microM monensin alone was not cytotoxic to hRPE cells, a single 7-day treatment with monensin caused up to a 4.1-fold increase in antiproliferative potency of IT on proliferating hRPE cells (p < or = 0.0001). Enhancement was obtained with only a 1-hour exposure to 0.1 microM monensin (p = 0.0001). In contrast, IT (0.1-10,000 ng/ml) combined with monensin (0.01 microM) had minimal effect on density-arrested cells. IT with or without monensin did not inhibit proliferation of Rhesus monkey RPE cells. Our results indicate that monensin enhances the selective cytotoxic effect of IT on proliferating hRPE cells in culture. PMID- 8436011 TI - Effect of metabolic inhibitors and anaerobiosis on rat lens. AB - The effect of the inhibitors of aerobic metabolism on the transport of rubidium and ATP content in rat lens has been studied under organ culture system. The inhibitors used were malonate, monofluoroacetate, cyanide, antimycin A, 2-heptyl 4-hydroxyquinoline-N-oxide (HQNO), 2,4-dinitrophenol (DNP) and dicumarol. All these compounds inhibited the transport of rubidium, reflecting a decrease in the ability of the lens to transport potassium. The levels of ATP also decreased. The results were similar to those obtained under anaerobic conditions where the lenses were incubated in a nitrogen atmosphere without the inhibitors. The degree of inhibition observed by the metabolic inhibitors as well as by anaerobiosis indicate that the rat lens depends substantially on aerobic oxidation for its energy needs, unlike bovine and rabbit lenses studied before. PMID- 8436012 TI - Effect of photoreceptor outer segment disk shedding on myeloid body formation in the retinal pigment epithelium of the leopard frog. AB - To test the hypothesis that myeloid body (MB) formation results from the shedding of retinal photoreceptor outer segments and the consequent degradation of lipids derived from outer segment disk membranes, the effect of massive outer segment shedding and the disruption of such outer segment shedding on MB formation were examined in the leopard frog. Light entrained frogs were first placed in constant light (700 lux) for 48 hours to inhibit shedding, followed by a 1.5 hours dark priming either in vivo or in vitro, and then returned to light for an additional 4 hours which results in massive outer segment shedding. To serve as a control, the effect of shedding disruption on MB formation was assessed in vivo using light manipulation to inhibit shedding, or mechanical removal of the neurosensory retina in vitro. The results indicate that although the phagosome numbers were clearly elevated in the samples taken from either in vivo or in vitro eye-cup preparations where outer segment shedding had been stimulated, there was no significant concomitant increase in Mbs number over controls kept under constant light for 48 hr or constant light 48 hr plus 1.5 hr in dark, where MBs represent approximately 5% of the total RPE cell area. In contrast, when shedding was interrupted either by removal of the neural retina immediately after in vitro eye cups were returned to light or by maintaining frogs in dark without light stimulation, the RPE cells contained very few phagosome, yet in both conditions RPE cells showed a two-fold increase in MB area over the shedding-stimulated controls (p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8436013 TI - Adrenergic innervation of the choroid and iris in diabetic rats. AB - We compared the distribution and density of ocular adrenergic nerves in rats after 3 to 13 months of streptozotocin diabetes and in age-matched control animals to learn whether diabetic sympathetic neuropathy is evident in the eye as it is in other organs. An aqueous aldehyde method for histochemical demonstration of catecholamines provided a clear and complete view of the adrenergic innervation in whole flat preparations of choroid and iris. In the choroid, a dense plexus of varicose nerve fibers invested all of the branching arterial blood vessels. A less dense network of nerves was present in the choroidal stroma between the arteries, but there was no obvious association of nerves with the venules draining choroidal capillaries. Using a stereological method to measure the density of the adrenergic plexus of choroidal arteries, we found the mean innervation density to be normal in diabetic animals sampled at 3, 9, and 13 months after onset of hyperglycemia. Microscopic examination also failed to reveal diabetes-associated changes in the diffuse stromal nerves of the choroid or in the rich adrenergic innervation of the iris. Diabetes of relatively long duration, therefore, does not obviously affect the density or distribution pattern of catecholamine-containing nerves supplying the rat eye. PMID- 8436014 TI - Purification of phospholipid hydroperoxide glutathione peroxidase from bovine retina. AB - A low molecular size peroxidase with a high affinity for phospholipid hydroperoxide was purified from bovine retina by sequential extraction with low and high ionic strength buffer, followed by ammonium sulfate fractionation, chromatography on an ultraspherogel column and Protein PAK-SP column. The purified enzyme has a low Km (0.011 mmol/L) for phospholipid hydroperoxide, and a high Km (1.37 mmol/L) for glutathione. Glutathione oxidation was competitively inhibited by vitamin E, Ki = 0.019 mmol/L. The retinal PHGPX is different from the PHGPX purified by others from heart and liver in molecular size. The molecular size estimated by gel filtration chromatography is below 6 kDa. PMID- 8436015 TI - Modern management of acute myocardial infarction. PMID- 8436016 TI - Effect of head position on the dynamics of the upper esophageal sphincter and pharynx. AB - Due to limitations in available technology it has been difficult to obtain data on upper esophageal sphincter (UES) and pharyngeal (P) function under varying physiologic conditions. We used a manometry system with solid-state intraluminal transducers, including a circumferential sphincter transducer, and computer analysis to measure pressure changes in UES and P during wet (5 ml H2O) swallows as the head was moved through a 75 degree arc in nine normal volunteers. UES residual pressure increased markedly and duration of UES relaxation decreased with increasing head extension. Similar decreases were also seen with time between P peak and both UES nadir and UES end. There were no changes in either pharyngeal peak pressures or the duration of the pharyngeal contraction. Head extension produces major changes in UES relaxation and UES/P coordination. These effects may be clinically important when feeding neurologically impaired patients. PMID- 8436017 TI - Normal laryngeal valving patterns during three breath-hold maneuvers: a pilot investigation. AB - Synchronized videonasendoscopy and respiratory recordings were conducted in six healthy male subjects to evaluate activity of the arytenoid cartilages, true vocal folds, false vocal folds, and epiglottis during repeated trials of three breath-hold maneuvers: EASY hold, INHALE HARD hold, and INHALE/EXHALE HARD hold. Five of the six subjects demonstrated maximal laryngeal valving on the HARD breath-hold conditions. One subject showed maximal laryngeal valving on the EASY hold condition, and rarely demonstrated any medial displacement or contact of the laryngeal valves on either effortful breath-hold maneuver. Arytenoid approximation and true vocal fold closure were produced consistently by the majority of subjects on all breath-hold maneuvers, but false vocal fold approximation and anterior arytenoid tilting were accomplished by the majority of subjects only during the effortful breath-hold conditions. Intratrial and intersubject variation indicated that presence or degree of laryngeal valving cannot be assumed during a breath-hold maneuver. We conclude that videonasendoscopy has merit in assessing a patient's laryngeal valving ability and progress in effectively using a breath-hold maneuver for safe swallowing function. PMID- 8436018 TI - Ligaments of the larynx and the adjacent pharynx and esophagus. AB - Two ligament systems of the larynx are demonstrated by dissection. The suspensory ligament of the esophagus is attached to the posterior aspect of the cricoid cartilage and is also a part of the fascial sheath which is common to the hyoid, thyroid, and cricoid. The ligaments at the inner margins of the vocal, ventricular, and aryepiglottic folds are distinctive in site and, inferentially, in function. The aryepiglottic ligaments join at the incisura between the arytenoid cartilages and are continued as the corniculopharyngeal ligament which splays into the flexible tissues in the anterior wall of the hypopharynx, posterior to the suspensory ligament of the esophagus. These ligament systems are involved in two different actions in swallow. The gross superior and anterior motions of the larynx are transmitted to the esophagus by the suspensory ligament, so that the esophagus is elevated in relation to the bolus and is also opened. These esophageal displacements resemble, in effect, the swallow displacements of the pharyngoesophageal segment and of the constrictor wall of the hypopharynx. The marginal ligaments of the laryngeal folds help to implement the constriction and closure of the larynx during swallow. By anatomical inference, the corniculopharyngeal ligament effects vertical traction within the flexible tissues of the anterior wall of the hypopharynx. PMID- 8436019 TI - Swallowing, speech, and brainstem auditory-evoked potentials in spasmodic torticollis. AB - To explore the controversial "brainstem theory" of spasmodic torticollis, eight consecutively referred patients were examined. Three independent examinations were conducted on the same day: a videofluoroscopic barium swallowing examination, an instrumental speech examination, and a brainstem auditory-evoked potential (BAEP) analysis. Swallowing was normal in two patients; speech physiology, in five; and BAEPs, in all. Normal BAEPs refute the brainstem theory, while abnormalities of speech and swallowing temper this conclusion. Several alternative explanations are proposed. PMID- 8436020 TI - Kinematic pharyngeal transit times in myopathy: evaluation for dysphagia. AB - Measurement of kinematic pharyngeal transit times, a new videofluoroscopy technique, provides useful quantitative data to supplement the qualitative data previously available from videofluoroscopy swallowing studies. Kinematic pharyngeal transit times have not previously been reported for subjects with myopathy. This study demonstrates the use of quantitative kinematic pharyngeal transit times for dysphagia evaluation in 15 patients with myopathy. The successful treatment of dysphagia by cricopharyngeal myotomy is reported in two patients with limb-girdle syndrome. PMID- 8436021 TI - Hypoxemia during oral feedings in adults with dysphagia and severe neurological disabilities. AB - Signs of respiratory distress including coughing, choking, and gagging are not uncommon during oral feedings in patients with severe dysphagia. Aspiration pneumonia and chronic lung disease are recognized complications. Pulse oximetry, respiratory inductance plethysmography, and nasal airflow measurement by thermistors are accurate noninvasive methods of monitoring cardiopulmonary adaptation during oral feedings in patients with severe dysphagia. We report significant, previously unrecognized, acquired hypoxemia during oral feedings in two patients with severe cerebral palsy and one with multiple sclerosis. The episodes of hypoxemia occurred only while swallowing specific food textures. Periods of hypoxemia most probably resulted from aspiration during oral feedings. Cardiopulmonary adaptation may prove to be an important consideration in decisions regarding the method and advisability of continued oral feedings in patients with severe dysphagia. PMID- 8436022 TI - Nutrition and nutritional requirements for the older adult. AB - Establishing reliable nutrient requirements for individuals over the age of 65 years is a difficult task. Research on nutrient requirements in the aged is sparse and often contradictory. However, there are important clues in the literature suggesting that requirements for certain nutrients are altered with age and that preventable nutrient deficiencies exist. Energy expenditure and caloric intake typically decline with age. Unless nutrient density of the diet improves, a parallel decline in vitamin and mineral intake is inevitable. Deficiencies or suboptimal intakes of water-soluble vitamins, vitamin D, calcium, zinc, copper, chromium, and water are reported in groups of older adults. Marginal nutrient deficiencies in this population may easily go undetected and contribute to morbidity. PMID- 8436023 TI - Acute pharyngoesophageal dysphagia secondary to spontaneous hemorrhage of a parathyroid adenoma. AB - Spontaneous hemorrhage of a parathyroid adenoma is a rare occurrence which may manifest with a variety of symptoms including cervical pain, hoarseness, respiratory distress, and dysphagia. We report a case of an elderly woman with a parathyroid adenoma diagnosed 10 years ago and for which she had refused surgery. Throughout this period her hypercalcemia was carefully monitored, and she experienced no symptoms or adverse sequelae from her disease. However, the patient subsequently presented with a 1 day history of a sore throat and a nonproductive cough followed by the acute onset of dysphagia. At this time she was found to have an anterior neck hematoma extending to the midthorax. Computerized tomography and direct laryngoscopy were suggestive of the diagnosis and neck exploration confirmed the presence of a large hematoma beginning at the site of the 3 x 4 cm parathyroid adenoma and extending into the left strap musculature. We report this case of spontaneous hemorrhage of a cervical parathyroid adenoma to bring to mind a rare etiology of acute pharyngoesophageal dysphagia. PMID- 8436024 TI - Origin and truth: young children's understanding of imaginary mental representations. AB - In 2 studies, we address young children's understanding of the origin and representational relations of imagination, a fictional mental state, and contrast this with their understanding of knowledge, an epistemic mental state. In the first study, 54 3- and 4-year-old children received 2 tasks to assess their understanding of origins, and 4 stories to assess their understanding of representational relations. Children of both ages understood that, whereas perception is necessary for knowledge, it is irrelevant for imagination. Results for children's understanding of representational relations revealed intriguing developmental differences. Although children understood that knowledge represents reality more truthfully than imagination, 3-year-olds often claimed that imagination reflected reality. The second study provided additional evidence that younger 3-year-olds judge that imaginary representations truthfully reflect reality. We propose that children's responses indicate an early understanding of the distinction between mental states and the world, but also a confusion regarding the extent to which mental contents represent the physical world. PMID- 8436025 TI - An attributional intervention to reduce peer-directed aggression among African American boys. AB - An attributional intervention was designed to reduce aggressive males' tendency to attribute hostile intentions to peers following ambiguously caused peer provocations. African-American elementary school boys (N = 101), aggressive and nonaggressive, were randomly assigned to the attributional intervention, an attention training program, or a no-treatment control group. Data were collected on subjects' attributions about hypothetical and laboratory simulations of peer provocation, disciplinary referrals to the school office, and teacher ratings of aggressive behavior. Aggressive subjects in the attributional intervention were less likely to presume hostile intent by peers in hypothetical and laboratory simulations of ambiguous provocation. They were also less likely to endorse hostile retaliation on judgment measures and to engage in verbally hostile behaviors in the laboratory task. Further, intervention subjects were rated as less aggressive by their teachers following the treatment. Both the benefits of attributional change and its limitations in the African-American population are discussed. PMID- 8436026 TI - Characteristics of aggressive-rejected, aggressive (nonrejected), and rejected (nonaggressive) boys. AB - 95 boys at 3 developmental levels (ages 6-8, 8-10, 10-12) were selected on the basis of sociometric and aggression ratings to represent 4 groups: (1) aggressive and rejected, (2) aggressive (not rejected), (3) rejected (not aggressive), or (4) neither aggressive nor rejected. Behavioral observations, teacher ratings, peer ratings, and open-ended peer interviews were collected to characterize the behaviors of these boys in 3 social domains (conduct problems, sociability/withdrawal, and adaptability/responsivity to peer expectations). Distinct problem profiles emerged. Aggressive-rejected boys exhibited more diverse and severe conduct problems that did aggressive boys, along with greater deficiencies in the domain of adaptability. Nonaggressive rejected children were considered by teachers and peers to be shy and passive, deficient in prosocial behaviors, atypical, and socially insensitive. Grade-level decreases in physical aggression and increases in peer-reported atypical/insensitive behaviors corresponded to developmental differences in group characteristics. PMID- 8436027 TI - The effects of physical abuse on children's social relationships. AB - Social behavior and peer status of 87 physically abused 8-12-year-old urban children were compared with those of 87 case-matched nonmaltreated classmates. Peer nominations and peer ratings were collected in classrooms, social networks were assessed by child interview, family variables were assessed by interviewing mothers, and behavior problems were rated by parents and teachers. Significant findings were that abused children had lower peer status and less positive reciprocity with peers chosen as friends; they were rated by peers as more aggressive and less cooperative and by parents and teachers as more disturbed; and their social networks showed more insularity, atypicality, and negativity. Social behavior as perceived by peers accounted for a significant portion of the variance in social status; global disturbance measures did not add to this association. Results are discussed in terms of a context of family violence in the development of social maladjustment. PMID- 8436028 TI - The academic, personality, and physical outcomes of only children in China. AB - Representative samples of 1,000 schoolchildren from 4 Chinese provinces were surveyed to compare the outcomes of only children to those of firstborn and later born children. The children's ages ranged from 8 to 17 years, with half of the sample in the third grade and the other half in the sixth grade. 3 types of outcomes were considered. In terms of academics, differences between only children and others were found in 3 of the 4 provincial samples, with onlies being most likely to outscore others in verbal tests. In terms of personality evaluations, very few only-child effects were found. In 2 of the 4 provincial samples, only children were found to be taller or to weigh more than others. Taken together, these results suggest that the one-child policy in China is not producing a generation of "little emperors." PMID- 8436029 TI - Children's concordant emotions and cognitions in response to observed emotions. AB - Children's emotional and cognitive responses to observed scenarios were examined in 2 studies (N = 138 5-13-year-olds) investigating hypothesized developments in concordant emotion with stimulus persons, cognitive attributions for these emotions, and the effects of emotional intensity in self and stimulus persons. Results across studies confirmed age-related increases in children's emotional and cognitive responses. There were limited increases with age in concordant emotion, and continuous increases in the frequency and kinds of attributions explaining such emotion. Results also confirmed a model ordering expected developments in children's emotion attributions. As expected, stimulus persons' emotional intensity correlated with children's emotion intensity and affect match. However, as expected, empathy with others was lower when children's own intensity was higher than stimulus persons'. Present findings contribute to investigations of children's understanding of emotions and have implications for developmental studies of empathy. PMID- 8436030 TI - Children's appraisals of marital conflict: initial investigations of the cognitive-contextual framework. AB - 2 studies examined children's appraisals of marital conflict. In Study 1, 45 11- and 12-year-olds reported cognitive, affective, and coping responses to conflicts varying in content and intensity. When conflict concerned the child, children reported more shame and fear of being drawn into the conflict and tended to endorse coping responses that involved direct intervention in it. More intense conflicts led to greater negative affect and perceived threat. In Study 2, 112 12 year-olds responded to conflicts that included a parent-blaming or child-blaming explanation or gave no explanation for the conflict. Explanations that absolved the children of blame for the conflict decreased their fear of becoming involved in the conflict and their desire to intervene in it. These findings show that appraisals of marital conflict are influenced by its content, intensity, and cause and suggest that the meaning of conflict to children is an important determinant of its impact. PMID- 8436031 TI - Attachment and emotion regulation during mother-teen problem solving: a control theory analysis. AB - We present a control theory analysis of adolescents' attachment strategies in the Adult Attachment Interview (AAI). In Study 1, Q-sort prototypes for secure/anxious and deactivating/hyperactivating strategies were used to differentiate between Main and Goldwyn's AAI classifications. In Study 2, we examined how AAI strategies were associated with emotion regulation during mother teen problem solving. 4 aspects of mother-teen problem solving (dysfunctional anger, support/validation, avoidance of problem solving, and maternal dominance) were used to predict teens' AAI strategies. Teens with secure strategies engaged in problem-solving discussions characterized by less dysfunctional anger and less avoidance of problem solving. In addition, attachment security showed a curvilinear relation with maternal dominance, indicating that secure teens maintained balanced assertiveness with their mothers. Teens with deactivating strategies engaged in problem-solving interactions characterized by higher levels of maternal dominance and dysfunctional anger. The contribution of attachment strategies to teens' autonomy and to transformations in mother-teen relationships is discussed. PMID- 8436032 TI - Changes in parents' work status and adolescents' adjustment at school. AB - The effects of change in parental work status on early adolescents' school adjustment before and after the transition to junior high school were examined in a 2-year longitudinal study. Data were gathered from 883 adolescents, their mothers, and teachers. Based on patterns of change or stability in parental work status during the 2 years of the study, 4 groups were compared: deprived, declining, recovery, and stable families. With parents' education controlled, teachers said that adolescents in deprived and declining families were less competent than their peers in stable or recovery families. In addition, adolescents whose parents experienced a decline in work status were the most disruptive in junior high school. While most students had difficulty adjusting to junior high school, the transition was particularly difficult for those students whose parents were simultaneously dealing with changes in work status. PMID- 8436033 TI - Parenting during the second year: effects of children's age, sex, and attachment classification. AB - 70 2-parent families with 12-month-old infants and 67 2-parent families with 18 month-old toddlers participated in the study. Mothers and fathers participated in separate interviews and filled out questionnaires on family and child behaviors. Mothers and their children participated in the Ainsworth Strange Situation, and the families were observed for a total of 4 hours in their homes. Families were compared on composite measures of family environment variables, parents' perception of their children, and on process variables from home observations. Family differences in environmental stress and marital adjustment showed no effects for attachment classifications, although parents of 12-month-olds reported greater marital adjustment and more pleasure in parenting than parents of 18-months-olds. Both mothers and fathers reported that children classified as resistant were more difficult on several temperament measures. During home observations, 12-month-old children received more positive responses from mothers, and 18-month-old children received more instructions and directions from both parents. Insecure boys (both avoidant and resistant) received the least instructions and directions from both parents, but insecure-avoidant girls received the most instruction from fathers. PMID- 8436034 TI - Age differences in understanding of disease causality: AIDS, colds, and cancer. AB - The development of concepts of disease causality was explored by asking 9-, 11-, and 13-year-olds and college students about risk factors for AIDS, colds, and cancer. Their knowledge became more accurate and differentiated with age. Although younger children knew a good deal about what causes each of the diseases, they lacked knowledge of what does not cause them, often inferring that risk factors for one disease, especially AIDS, cause other diseases as well. Knowledge of true risk factors for a disease was largely independent of knowledge of non-risk factors, and knowledge of one disease was largely independent of knowledge of another. These findings provide clues as to how disease understandings evolve with age and suggest that health educators must both understand students' current knowledge structures and explicitly teach students to make important differentiations between risk and non-risk factors for a given disease and between distinct diseases. PMID- 8436035 TI - Memory for gender-consistent and gender-inconsistent event sequences by twenty five-month-old children. AB - Gender-schema theory predicts that, based on a rudimentary understanding of gender (e.g., self-labeling), children will invoke gender schemata in the processing of information. In older children, one indication of schematic processing is differential memory for schema-consistent versus schema inconsistent material. Due to a lack of appropriate measures, evidence of very early use of gender schemata has been limited. In the present study, elicited imitation was used to assess 25-month-old girls' and boys' immediate and delayed recall of sequences depicting female-stereotyped, male-stereotyped, and gender neutral activities. At immediate and delayed testing, girls showed equivalent levels of recall of all 3 sequence types. Boys showed superior recall of male- relative to female-stereotyped sequences; their recall of gender-neutral sequences was equivalent to that of male-stereotyped ones. Results indicate that, at least for boys, use of gender schemata is evident by 25 months of age. Possible explanations for the absence of a clear effect for girls are discussed. PMID- 8436036 TI - Perceiving the affordance of contact in four- and five-month-old infants. AB - The focus of this study was on the ability of infants to perceive whether an object is positioned at a distance that would make contact possible. As a toy was presented, sometimes within and sometimes beyond reach, the initiation of reaching and leaning forward was scored. Infants were divided into leaning and nonleaning groups. Both leaning and nonleaning 5-month-olds changed their behavior dramatically when the object was placed beyond, as opposed to within, reach. The nonleaners showed a decline in reaching when this boundary for contact was crossed. The "leaners" did not; rather, they began to lean forward. These results suggest that 5-month-olds use information for the affordance of contact. 4-month-olds provided less evidence that arm length regulates reaching. 5-month old infants acted as if they not only had some sensitivity to the absolute distance of an object but also to the effect that leaning forward has on their ability to make contact with a distant object. PMID- 8436037 TI - Understanding category members as "the same sort of thing": explicit categorization in ten-month infants. AB - Although it is often acknowledged that classification exists in the first year of life, it has been suggested that infants are capable only of implicit categorization, recognizing that something is or is not familiar. In contrast, older children are thought to compare the stimuli or objects they categorize and to explicitly equate different category members. 2 habituation experiments were conducted in an attempt to determine whether 10-month-old infants are capable of explicit categorization. The approach taken was to insert nonmembers into the familiarization sequence in a categorization task. The nonmembers were designed so as to have a predictable effect on infants' performance whether or not these stimuli were included as infants processed the categorical information. The results suggest that infants do explicitly equate category members. Infants appeared to disregard the nonmembers in the familiarization sequence, basing their categorization response instead on the set of instances that were "the same sort of thing." PMID- 8436038 TI - A meta-analysis of infant habituation and recognition memory performance as predictors of later IQ. AB - A meta-analytic review of the literature on infant habituation and recognition memory performance as predictors of later IQ suggests several conclusions: (1) Habituation and recognition memory assessments made on a variety of risk and nonrisk samples in the first year of life predict later IQ assessed between 1 and 8 years of age with a weighted (for N) average of normalized correlations of .36 or a raw median correlation of .45. (2) The size of the predictive correlation is essentially the same for habituation and for recognition memory paradigms. (3) This prediction phenomenon is not obviously associated solely with one laboratory, one particular infant response measure, or a few extremely disordered infants. (4) The level of prediction to childhood IQ is substantial given the reliability of the infant measures. (5) Predictions are somewhat higher for risk than for nonrisk samples. (6) Predictions are consistently higher than for standardized infant tests of general development for nonrisk but not for risk samples, and they are not consistently higher than predicting from parental education and socioeconomic status or a few other infant behaviours for nonrisk samples. (8) Coefficients may be higher when the predicting assessments are made between 2 and 8 months of age than earlier or later, but prediction coefficients are remarkably consistent across the observed outcome age period of 2-8 years. PMID- 8436039 TI - Stability of intelligence from preschool to adolescence: the influence of social and family risk factors. AB - Intelligence scores of children in a longitudinal study were assessed at 4 and 13 years and related to social and family risk factors. A multiple environmental risk score was calculated for each child by counting the number of high-risk conditions from 10 risk factors: mother's behavior, mother's developmental beliefs, mother's anxiety, mother's mental health, mother's educational attainment, family social support, family size, major stressful life events, occupation of head of household, and disadvantaged minority status. Multiple risk scores explained one-third to one-half of IQ variance at 4 and 13 years. The stability between 4- and 13-year environmental risk scores (r = .77) was not less than the stability between between 4- and 13-year IQ scores (r = .72). Effects remained after SES and race, or maternal IQ, were partialled; multiple risk was important in longitudinal prediction, even after prior measurement of child IQ was accounted for; the pattern of risk was less important than the total amount of risk present in the child's context. PMID- 8436040 TI - Parent reports of behavioral and emotional problems among children in Kenya, Thailand, and the United States. AB - The behavioral and emotional problems children develop may differ from one cultural context to another. We explored this possibility, comparing 11-15-year old Embu children in Kenya, Thai children, African-American children, and Caucasian-American children. Standardized parent reports on 118 problems revealed 62 significant (p < .01) culture effects. Caucasian-Americans were rated particularly high on undercontrolled problems (e.g., arguing, disobedient at home, cruel to others). Embu children were rated particularly high on overcontrolled problems (e.g., fears, feels guilty, somatic concerns), largely because of the numerous somatic problems reported. The findings may relate to the strict emphasis on compliance and obedience among the Embu, as opposed to the greater independence permitted in the United States. But alternative interpretations are discussed as well, including the effects of parent sensitivities and Third World living conditions. PMID- 8436041 TI - [Society of specialist professional organizations on the structure of family specialist services]. PMID- 8436042 TI - [Current aspects of surgery]. PMID- 8436043 TI - [Between two fronts--the professional society as a bond in the controversy about ambulatory surgery]. PMID- 8436044 TI - [Medicolegal importance of the BGH decision on patient education responsibility in blood transfusion. Report of the results of a workshop 28-29 August 1992 in Nurnberg]. PMID- 8436045 TI - [Ascites and liver transplantation]. PMID- 8436046 TI - [Scoring systems in the surgical intensive care unit. II]. PMID- 8436047 TI - [Diagnosis and surgical treatment of extra-adrenal pheochromocytoma]. AB - From 1980 until 1991 10 patients were operated upon a paraganglioma: 5 patients with an encapsulated solitary tumor, two with infiltrating tumors and 3 with metastatic disease. The diagnosis of a catecholamine-producing tumor was most reliably made by norepinephrine analysis in urine and serum. The localization of the tumor was diagnosed in 9 of 10 cases by sonography and CT-scan. In 9 patients the tumor was excised completely, 4 times by extended resections. Whereas 4 out of 5 patients with an encapsulated solitary paraganglioma live to date without recurrence, all 3 patients suffering from metastatic disease had recurrent disease within one year postoperatively. A differentiated operative therapy of paragangliomas based on a clinical characterization is proposed: Encapsulated paragangliomas should always be excised. For solitary infiltrating tumors an extended resection may be necessary. This seems not to be justified for multiple infiltrating or metastasizing paragangliomas. Thus, only a reduction in size may be adequate for these tumors. PMID- 8436048 TI - [Preoperative assessment of depth of infiltration of rectal tumors by staging, endosonography and magnetic resonance tomography. A prospective study]. AB - The choice of individual therapy for rectal tumours requires the pretherapeutic assessment of the depth of infiltration of the tumour. Fourty-four patients with rectal tumour were evaluated preoperatively by digital examination, endosonography and magnetic resonance imaging (MRI). Test results were compared with the postoperative histological examination. In digitally accessible tumours clinical staging had an accuracy rate of 85%. The sensitivity of endosonography was 83%, compared with 54% for MRI. Our findings suggest that endosonography may be more accurate as MRI, especially for rectal adenomas and early carcinomas. PMID- 8436049 TI - [Bowel preparation for surgery of the anus, rectum and colon]. AB - Successful bowel preparation for proctologic surgery is not schematic possible for all patients. Quality of cleansing after whole gut irrigation in women for example with chronic constipation is not always as efficient as in other patients. Two techniques for preparation of the colon were compared in a controlled trial. Fifty given the strong laxative Prepacol and fifty with whole gut irrigation. Significantly more patients suffered from vomiting and postoperative infections (translocation?) following irrigation. Prepacol preparation was well tolerated, showed a similar quality of cleansing and only a small discomfort. PMID- 8436050 TI - [Color-coded duplex sonography in diagnosis of primary varicose veins and recurrent varicose veins]. AB - Varicose vein surgery, adapted to obtaining condition, requires highly accurate preoperative diagnostics as a basic requirement. The Colour Doppler ultrasound allows one to ascertain the morphological, topographical and functional condition of the venous system and thereby makes possible an operation appropriate for the stage. Thirty-six patients who preoperatively were subject to this examination could be clearly classified according to the localisation of the points of insufficiency; also existing insufficient perforans veins were identified. Eleven patients suffering from relapse varicose veins were examined. In the course of examination we identified crosse and parva relapses as well as perforans insufficiencies and subsequently removed them surgically. Our results definitely show that clinical use of colour Doppler ultrasound in the field of preoperative varicose vein diagnostics has considerable advantages compares with the hitherto existing methods and therefore should be applied more extensively. PMID- 8436051 TI - [Fournier's gangrene]. AB - Today Fournier's gangrene ranks among necrotizing fasciitis. Most of the cases reveal the origin of the disease (proctogenic, urologic, gynecologic). Untreated, the polybacterial synergistic infection will overwhelmingly spread along anatomically defined fascias of the pelvic floor. Thus the lethality rate is high, especially in patients with risk factors i.e. diabetes, alcoholism, arterial occlusive disease, chronic consumptive disorders and obesity. Only by instant and radical surgical excision of the total gangrenous tissue the spreading of the disease and the developing of sepsis can be stopped together with calculated antibiotic therapy and intensive care. Mutilating operations (i.e. penectomy, orchiectomy) are seldom necessary; thus plastic reconstructions will show good results both in function and cosmetic. Based on the experience with 6 patients, a pathogenic concept, concerning both diagnosis and therapy, is presented: after radical emergency surgery in the first risky stage, an elective approach can safely be performed in a second stage for the repair of functional lesions. PMID- 8436053 TI - [Surgical indications in duodenal tumor]. PMID- 8436052 TI - [Fournier's gangrene. Case report and review of the literature]. AB - Fournier's gangrene is a rare condition, far from being 'idiopathic', which must be taken seriously and which is, although at first manifesting itself only locally, a generalized condition with high mortality and--unless recognized- taking a rapid course with lethal outcome. Many risk factors have been recognized which favor an often lethal outcome. Although oftentimes not recognized, a port of entry is always present and haemolytic streptococci are as a rule involved. Since Fournier the age limit has moved to the 5th and 6th decades. Early recognition, prompt and aggressive surgical treatment and antibiotic coverage are mandatory to offer patients a chance to survive. PMID- 8436054 TI - [Conservative therapy of ascites]. PMID- 8436055 TI - [Puncture metastasis after percutaneous endoscopic gastrostomy]. PMID- 8436056 TI - [A cerebrospinal fluid fistula as a rare complication of anterior lobe-chest wall resection for squamous epithelial cancer of the lung]. PMID- 8436057 TI - Criminality in a sample of drug abusers in Greece. AB - Criminality as expressed by self-reported arrests and convictions was studied in a sample of 294 drug--mainly heroin--abusing subjects, 77.6% of whom had been arrested and 57.1% convicted. The majority had more than one arrest or conviction for a variety of crimes. Arrests and convictions for other than drug offences outnumbered the drug offences. Only a minority of the subjects were responsible for the majority of criminal acts. In half of the subjects, involvement in criminality predated initiation to heroin use. Gender, polydrug use, unemployment, low education level--not injecting heroin as main mode of use--were found to be among the main factors significantly predicting criminality. PMID- 8436058 TI - Crime and drug use among applicants for methadone maintenance. AB - The relationship between crime and drug use was examined in 313 Australian opioid addicts who applied for entry to methadone treatment. More than 90% of them had recorded one or more convictions for property or drug offences. Subjects' self reported convictions were moderately correlated with convictions recorded by the police. Men were more likely to begin their opioid use at or after their first criminal conviction, while women were more likely to begin offending after they used opioids. The rate at which subjects accrued convictions for property offences declined as they grew older and the earlier a subject's first exposure to the criminal justice system the higher the rate at which they accrued convictions. PMID- 8436059 TI - Clinical evaluation of a citric acid inhaler for smoking cessation. AB - In this study, we evaluated the efficacy of a hand-held inhaler as an adjunct to a smoking cessation behavioral program. The inhaler delivered a citric acid aerosol with tobacco smoke flavor. Seventy-four smokers were recruited for a 3 week smoking cessation trial. During the first 12 days of the cessation period, smokers used the citric acid aerosol inhaler instead of a cigarette whenever the urge to smoke occurred. The citric acid inhaler significantly reduced CO levels and enhanced rates of smoking abstinence for those with higher than average (34.2 ppm) baseline end-expired carbon monoxide (CO) levels. Craving for cigarettes and negative affect were also alleviated by the citric acid aerosol. These results suggest that the citric acid aerosol may promote successful smoking reduction or cessation in a subgroup of smokers and relieves withdrawal symptoms such as craving for cigarettes, a symptom difficult to treat with currently available nicotine replacement techniques. PMID- 8436060 TI - Effects of three monoamine uptake inhibitors on behavior maintained by cocaine or food presentation in rhesus monkeys. AB - Rhesus monkeys (n = 6) were surgically prepared with double lumen i.v. catheters and the effects of continuous infusion of the monoamine reuptake blockers mazindol, sertraline and fluoxetine were examined on behavior maintained by food presentation or i.v. cocaine injections. Under baseline conditions, lever pressing was maintained under a three-component multiple schedule of reinforcement in which food (1-g banana-flavored pellets) was available for 600 s under a fixed-ratio 30 schedule in the first and third components. In the second component, the dose of cocaine that maintained maximum rates of responding (0.03 or 0.05 mg/kg per injection) was available for 1800 s under a fixed-ratio 30 schedule. There was a brief time-out after each reinforcer. When behavior was stable, mazindol (0.4-3.2 mg/kg per 24 h), sertraline (0.1-8.0 mg/kg per 24 h) or fluoxetine (0.4-3.2 mg/kg per 24 h) was administered continuously via the second lumen of the double lumen catheter. Mazindol was administered for the same number of sessions that were required for responding to decline to low levels when the monkeys were allowed to self-administer saline [5-13] while sertraline and fluoxetine were administered for a minimum of 21 days. Baseline conditions were reinstated between doses of each drug. Each drug decreased cocaine-maintained responding in a dose-related manner. In most cases, food-maintained responding was disrupted at doses equal to or lower than those that decreased cocaine maintained responding. Additionally, the higher doses of each drug decreased food intake outside the daily sessions. These results suggest that monoamine uptake blockers with prominent effects on either dopamine or serotonin neurotransmission can decrease cocaine self-administration but only at doses that also affect behavior maintained by other reinforcers. PMID- 8436061 TI - The effect of chronic ethanol intake on brain NGF level and on NGF-target tissues of adult mice. AB - The effect of ethanol consumption on the forebrain and hypothalamus of adult mice was investigated. A consistent decrease of biological activity and of nerve growth factor (NGF) immunoreactivity was observed in the hippocampus and hypothalamus of alcohol-treated mice. Biochemical studies also indicate that chronic ethanol intake causes a reduction in the level of choline acetyltransferase in the septum, hippocampus and striatum, but not in the cortex and other brain regions. This study provides evidence that long-term ethanol intake causes impairment of brain NGF level and of the cholinergic enzyme, regulated by NGF, suggesting that NGF synthesis and/or biological activity is affected in alcohol-related brain neuropathology. PMID- 8436062 TI - Opioid miosis: effects of lighting intensity and monocular and binocular exposure. AB - Opioid miosis--that is, pupillary constriction caused by opioids--is one of the most sensitive and frequently assessed objective indices of opioid effects. Pupillary size is also affected by lighting intensity and monocular or binocular exposures. This study is the first systematic examination and quantitative characterization of the effects of lighting intensity and exposure on opioid miosis. Seven patients received their usual daily dose of methadone (50-60 mg p.o.). Reflected light intensities were manipulated among 4, 16, 40, 80, 160, 240 foot-lamberts (fl). Pupil photographs of the right eye were obtained with the left eye closed and both eyes open in random counterbalanced order at each fl. Pupil photographs were obtained 15 min before methadone and 5, 15, 30, 45, 60, 90, 120 and 180 min after methadone. Peak methadone miosis was best detected under moderately dim interior lighting (4, 16 fl) 90 min after methadone. Pupil diameters were systematically larger with one eye closed than with both eyes open and the average difference was 0.35 mm. Pupil diameter decreased 1.0 mm with each log unit increase in lighting intensity. PMID- 8436063 TI - Effects of mazindol on behavior maintained or occasioned by cocaine. AB - The effects of mazindol, cocaine and D-amphetamine were studied in rhesus monkeys trained to self-administer cocaine, and in rats and squirrel monkeys trained to discriminate cocaine from saline. Non-contingent intravenous drug injections were administered to monkeys responding under a session consisting of a 5-min period during which lever-pressing produced food reinforcement and a 60-min session in which responding produced i.v. cocaine infusions (10 or 33 micrograms/kg per infusion). Acute i.v. injections of cocaine (0.1-1.7 mg/kg), D-amphetamine (0.1-1 mg/kg) and the dopamine re-uptake inhibitor mazindol (0.03-0.56 mg/kg) given 5 min before the session decreased self-administration of cocaine, but also decreased rates of behavior maintained by the presentation of food. In both rats and squirrel monkeys trained to discriminate cocaine from saline in a two-lever, food-maintained procedure, mazindol, cocaine and D-amphetamine substituted for cocaine in a dose-related manner. Despite a lack of selectivity to decrease cocaine self-administration as compared to behavior maintained by food, the present data provide some rationale for further consideration of mazindol as a potential pharmacotherapy for stimulant abuse, due to its relatively low abuse liability and cocaine-like discriminative stimulus effects. PMID- 8436064 TI - Future time perspective in current and previous injecting drug users. AB - Future time perspective (FTP) is a measure of an individual's ability to conceptualise the future which has been shown to be foreshortened in drug addicts. We studied 100 opiate injecting drug users (IDUs) in New South Wales, Australia, of which half were currently injecting and half were not. There was a significant difference between the two groups on FTP, with those currently injecting having a truncated FTP extension. Factor analysis of the FTP scale suggested that the dimensions of future time may differ between groups, with current injectors having a perspective of loss and isolation compared to the dimension of self-evaluation and self-acceptance in those not currently injecting. These data support previous studies which demonstrated truncated FTP, also demonstrating a difference in currently (as opposed to previously) IDUs and suggest that both extension of FTP and an alteration of the dimensions of FTP are associated with cessation of injecting and entry into treatment. PMID- 8436065 TI - [Closure of a persistent ductus arteriosus Botallo without thoracotomy]. AB - A persisting ductus arteriosus (PDA) was closed with the Rashkind occlusion system in 15 patients (12 children, aged 1.0 to 10.8 years, and three adults, aged 21, 33 and 56 years). The method consists of the implantation of a double umbrella of polyurethane foam mounted on platinum or steel wire introduced into the PDA via a transport catheter, the ductus being closed by thrombosing and epithelialization of the implant. The mean diameter of the PDA (as measured in the lateral aortogram) was 2.4 (1.4-5.3) mm. There were no complications of the procedure, nor any embolization or other serious complications. The PDA was completely occluded in eight patients, while a residual shunt remained in seven. In the oldest patient, aged 56 years, who had a residual shunt, increasing haemolysis required surgical closure of the ductus with a pericardial patch. These results indicate that, for patients weighing over 5 kg and with a ductus diameter of less than 10 mm, the closure method after Rashkind is a sparing and only slightly invasive procedure. PMID- 8436066 TI - [Is Helicobacter pylori gastritis a macroscopic diagnosis?]. AB - In a prospective study, gastroscopy and biopsies from the gastric antrum and body were undertaken in 100 consecutive patients (67 women, 33 men; mean age 58.6 [11 90] years) with unknown Helicobacter pylori status. None had been on any bacteria suppressing drugs. Main indications for gastroscopy were upper abdominal pain, dyspepsia, emesis and anaemia of unknown cause. The macroscopic criteria for the diagnosis of H. pylori gastritis were the presence of at least one of the following signs: (1) chronic antral erosions; (2) goose-pimple-like appearance of the antral mucosa; (3) spotty erythema in the antrum; (4) complex changes of the antral mucosa with both bizarre reddening and pale areas; and (5) increased areolar markings and diffuse or fine-spotty erythema in the mucosa of the body of the stomach. Four biopsies each from the antrum and body were examined with the urease quick-test, microscopically as smears, specific culture and histology as reference methods. 60 patients had H. pylori gastritis, recognized macroscopically in 59 (sensitivity 98.3%). A false-positive diagnosis was made in 10 of 40 H. pylori-negative patients (specificity 75%). The positive predictive value of macroscopic diagnosis was 85.5%, the negative predictive value 96.8%. PMID- 8436067 TI - [Fatal complications of a colon contrast enema due to erroneous insertion of the infusion catheter in the vagina]. AB - A 68-year-old woman was to have a barium enema of the colon to discover the cause of recurrent cramp-like symptoms in the lower abdomen. At the beginning of the examination the responsible radiologist saw, during a fluoroscopic check, that the contrast medium had not advanced beyond the region of the infusion catheter tip. Believing this to be due to blockage in the catheter he increased the infusion pressure. Suddenly the patient went into treatment-resistant shock and died. The autopsy revealed that the infusion catheter had by mistake been placed into the vagina. This had caused a tear in the vagina with resulting subperitoneal contrast-medium infiltration. Embolization of contrast medium to the lung was demonstrated both histologically and radiologically. The cause of death was the combined effect of the embolism and peritoneally induced vagal shock. PMID- 8436068 TI - [Prevalence of hereditary deficiency of antithrombin III, Protein C en Protein S]. PMID- 8436069 TI - [Immunodiagnostic and immunopathogenetic significance of anti-neutrophil cytoplasma antibodies]. PMID- 8436070 TI - [Duty to substantiate fee arrangements with persons authorized to receive assistance. Opinion of the Koblenz Regional High Court of 10-3-1991]. PMID- 8436071 TI - [Nitroglycerin ointment in erectile impotence?]. PMID- 8436072 TI - [Androgens and bone metabolism]. PMID- 8436073 TI - [Ergotamine-induced heart valve fibrosis]. PMID- 8436074 TI - [Organ-preserving therapy of invasive bladder carcinoma]. PMID- 8436075 TI - In vitro interaction of heavy metals with ouabain receptors in rat brain microsomes. AB - This study investigates the influence of heavy metals on ouabain-binding in presence of thiol (sulfhydryl) compounds. The data on in vitro effects of mercury (Hg), lead (Pb) and cadmium (Cd) showed significant inhibition of 3H-ouabain binding to microsomal membrane in a concentration-dependent manner. Maximum inhibition of 3H-ouabain binding was observed at 1 microM for Hg and 100 microM each for Pb and Cd. Preincubation with monothiol (L-cysteine or glutathione) or dithiol (dithiothreitol) protected inhibition of 3H-ouabain binding to the membranes by Hg or Pb. Dithiol but not monothiols partially protected Cd inhibition. The present data confirm that the heavy metals interact with ouabain receptors in a manner similar to SH-blocking agents and protection of metal inhibited 3H-ouabain binding by thiol compounds is metal specific. PMID- 8436076 TI - Dimethylformamide pharmacokinetics following inhalation exposures to rats and mice. AB - Whole-body inhalation exposures to N,N-dimethylformamide (DMF) were conducted with rats and mice. The exposure concentrations were 10, 250, and 500 ppm DMF. The exposure routines consisted of single 1-, 3-, or 6-hour exposures and ten 6 hour exposures (ten exposure days in 2 weeks). Area under the plasma concentration curve (AUC) values were determined following exposure for DMF and "N-methylformamide" ["NMF" represented N-methylformamide plus N-(hydroxymethyl)-N methylformamide (DMF-OH)]. The DMF AUC values increased 8- and 29-fold for rats and mice, respectively, following single six-hour exposures to 250 and 500 ppm DMF. These data are indicative of saturation of DMF metabolism. Peak "NMF" plasma concentrations for rats and mice, following single 6-hour exposures, did not increase as DMF exposure concentrations increased from 250 to 500 ppm. In addition, the "NMF" plasma levels in rats following a single 6-hour 500 ppm DMF exposure did not decay by 24 hours post exposure. These "NMF" plasma data also indicate saturation of DMF metabolism. Multiple exposures to 500 ppm DMF resulted in a 3- and 4-fold reduction in DMF AUC values for rats and mice, respectively, compared to AUC values following a single six-hour 500 ppm DMF exposure. This indicates enhanced metabolism of DMF resulting from multiple 500 ppm DMF exposures and together with saturation of DMF metabolism suggest using exposure levels below 500 ppm in a chronic bioassay. Selected plasma samples were simultaneously assayed for NMF and DMF-OH. The "NMF" values consisted of between 30 to 60 percent DMF-OH depending upon the exposure group (conversely NMF represented 30 to 60 percent of the "NMF" levels). Urinary analysis of all samples revealed DMF-OH represented over 90 percent of the summed DMF, DMF-OH and NMF quantities. PMID- 8436077 TI - Dimethylformamide pharmacokinetics following inhalation exposure in monkeys. AB - Male and female cynomolgus monkeys received whole-body inhalation exposures to dimethylformamide (DMF) at concentrations of 30, 100, and 500 ppm for 6 hours a day, 5 days a week over a 13-week period. Serial blood samples were drawn at the conclusion of the first day of exposure and following 15, 29, 57, and 85 days of testing. Area under the plasma concentration curve (AUC) values were determined for DMF and "NMF" [N-methylformamide (NMF) plus N-(hydroxymethyl)-N methylformamide (DMF-OH)]. Urine samples were also collected and assayed for DMF, NMF and DMF-OH. The systemic exposure to DMF increased disproportionately as the airborne DMF concentrations increased. DMF AUC values increased 19- to 37-fold in male and 35- to 54-fold in female monkeys as the inhalation concentrations increased 5-fold (100 to 500 ppm). These data are consistent with saturation of DMF metabolism as inhaled DMF concentrations increased from 100 to 500 ppm. AUC values, peak plasma concentrations, and plasma half-lives were essentially unaltered over the duration of the study within each exposure concentration tested. Estimated plasma half-lives ranged from 1 to 2 hours and 4 to 15 hours for DMF and "NMF" respectively. DMF was rapidly converted to "NMF" following 30 ppm exposures, with "NMF" plasma concentrations higher than DMF plasma concentrations at the 0.5 hour time-point. In plasma samples simultaneously assayed for DMF-OH and NMF, the concentration of DMF-OH exceeded, was equal to, or was less than NMF concentrations depending upon the plasma sample. DMF-OH was always the main urinary metabolite (56 to 95 percent) regardless of exposure level or time on study. PMID- 8436078 TI - Correlation between concentration of cholinesterases and the resistance of animals to organophosphorus compounds. AB - The molar concentrations of the catalytic sites of serum cholinesterase (ChE--EC 3.1.1.8.) and cholinesterases (ChEs-acetylcholinesterase (AChE)--EC 3.1.1.7. and ChE) from brain and perfused liver of male birds, rats, swine and sheep were determined. A positive correlation between the molar concentrations of the catalytic sites of ChEs and the resistance of the animals to some organophosphorus compounds (OPhCs) was found. In addition, the present study also showed that the difference of the molar concentrations of catalytic sites of ChEs in the brain, blood serum and liver can cause varied resistance to some OPhCs. PMID- 8436079 TI - Turns and averaging as static and dynamic measures of masseter EMG activity. AB - Surface EMG records from human masseter muscles were analyzed at various fractions of the maximum voluntary contraction (MVC). Frequencies of turns, or reversals of signal direction, and integrated or average rectified values were compared as quantitative measures of this type of data. Averaged signals were useful for within-study comparisons or for revealing dynamic changes in EMG during excitation or inhibition. However, averaged values depend strongly on signal amplitude (and thus on electrode characteristics and muscle size), and are not easily transferable between studies. Turns frequencies increased with contraction up to 75% MVC, and were less dependent on signal amplitude than were averages. Turns frequencies may thus be useful for quantitative comparisons between studies or between different muscles. PMID- 8436080 TI - Prognostic value of EMG in patients with lumbar disc herniation--a five year follow up. AB - The prognostic value of EMG in patients treated for lumbar disc herniation was evaluated in 80 patients, 55 were operated and 25 treated conservatively. All patients had an EMG examination before the initial hospitalization or operation. The patients were followed up one year and five years later. The outcome of the treatment was evaluated using a modified WHO handicap classification. The initial EMG finding had no prognostic significance in determining the outcome five years later. A normal EMG finding both at the one year and five year follow-ups was related to a good outcome. Signs of old neuropathy, large motor unit potentials and reduced interference pattern muscles were related to a poor outcome. The EMG findings predict the outcome for these patients only to a limited extent. The overall outcome seems to be influenced to a greater extent by psycho-social aspects than by qualitative aspects of the nerve root lesion detected by the EMG. PMID- 8436081 TI - F-wave study at different stimulation rates in upper motoneurone lesions. AB - F-wave duration, amplitude and persistence at different frequencies of the antidromic impulse (0.2-0.5-1-2 Hz) were determined in 18 patients with vascular hemiplegia and in 32 healthy subjects of both sexes in the same age range. In normal subjects F amplitude and persistence showed a significant increase as the stimulation rate increased; in spastic patients a small difference in F amplitude was only found for greater difference in stimulus frequencies, the persistence did not significantly changed at different stimulation rates. Individual cross correlation values (r) obtained for latency and duration, latency and amplitude, amplitude and duration did not show significant changes at different stimulation rates in patients and in controls. PMID- 8436082 TI - Assessment of motor conduction times using magnetic stimulation of brain, spinal cord and peripheral nerves. AB - Central conduction times (CCTs) in the motor pathways were assessed in normal subjects using a magnetic stimulus for the recording of cortical and spinal (Cv7 and L4-L5) Motor Evoked Potentials (MEPs) as well as F-waves in upper and lower limbs. M-responses of maximal amplitude could be reliably obtained by using a 4.5 Tesla coil and a stimulus intensity of 85% of the maximal output. It was found that the CCTs derived from the latency difference between cortical and spinal MEPs were, on average, 0.90 ms and 3.15 ms longer, respectively for upper and lower limbs, than those obtained by combining cortical MEPs and F-wave latency measurements. This difference is similar to that reported when electric stimulation is used to elicit F-waves and/or spinal MEPs. It suggests that motor root fibers are depolarized at a distance of 7.8 and 17 cm from the cord by a spinal magnetic stimulus applied respectively at Cv7 and L4-L5 levels. This study shows that magnetic stimulation alone permits to assess CCT in motor pathways with the same reliability as any of the other stimulation modalities hitherto proposed in literature. PMID- 8436083 TI - Comparison of event related potentials (ERPs) distributions obtained with three reference systems: linked binaural, mean reference, extracephalic. AB - Event related potentials (ERPs) to auditory and visual oddball paradigms were recorded from 19 scalp derivations in 10 controls. Three different reference systems were used: the linked earlobes (LE), the computer calculated mean reference (MR), and a calibrated sterno-vertebral extracephalic reference (EC). The distribution of ERPs was represented on single plane maps (quadratic interpolation, 4-NN method). With LE reference N2, P3a-P3b had no polarity reverted counterparts on the scalp. With EC reference a negativity was recorded on T3-T4 (and partly T5-T5) derivations with the same latency as P3a-P3b vertex component. With MR the N2, P3a-P3b components at vertex were paralleled by polarity reverted counterparts on anterior frontal, temporal and occipital derivations. PMID- 8436084 TI - Frequency analysis of the EMG from the quadriceps of anterior cruciate ligament deficient individuals. AB - A bilateral comparison of the peak torque generated by the quadriceps muscles during isokinetic muscle action at a joint angular velocity of 180 deg/sec was undertaken in 17 subjects with chronic anterior cruciate ligament (ACL) deficiency. The results allowed subjects to be separated into minimal and maximal deficit groups. A frequency analysis of the electromyographic signals of the vasti lateralis obtained during the peak torque tests was then undertaken. The results showed that the median frequency of the ACL deficient limb in the maximal deficit group was significantly (p < 0.05) decreased compared to the median frequency of the uninvolved limb and both limbs of the minimal deficit group. These results suggested that type II muscle fibre atrophy had occurred. The frequency analysis of EMG may provide a noninvasive technique of measuring relative fibre atrophy differences between legs. PMID- 8436085 TI - Causes of the instability of R3 component of electrically evoked blink reflex: role of the attention to the stimulus. AB - The causes of the spontaneous sharp amplitude variations of R3 component of electrically evoked blink reflex have been analyzed, in 10 subjects 24-30 years, in different experimental conditions: a) neutral condition, b) selective attention to the stimulus; distraction from the stimulus: c) by looking at a poster rich with images and d) by signaling from sequences of numbers three targets. In the situations where the subject does not play attention to the experimental set up, (a), or is distracted from it (c), the R3 response shows the maximal amplitude, whereas in condition of greater attention to the stimulus (b), R3 appears sharply reduced in amplitude. Where attentive levels are high but not focused on the stimulus (d), the reduction of the third reflex response is lesser. The reciprocal modifications with respect to the other responses R1 and R2 are also discussed. PMID- 8436086 TI - Electrodiagnosis of retrograde changes in carpal tunnel syndrome. AB - We measured evoked mixed nerve action potentials (EMNAP) in the forearm segment of 108 hands as an indicator of retrograde degeneration in the carpal tunnel syndrome (CTS). This was made by recording at the elbow and stimulating the median nerve 4 cm proximal to the wrist crease. The amplitude of this EMNAP decreased in proportion to the prolongation of the motor terminal latency (MTL) or the decrease in the amplitude of the compound muscle action potential (CMAP) from the abductor pollicis brevis (APB) muscle. This suggests that retrograde degeneration progresses as the severity of CTS increases. This decrease was also in proportion to the decrease in the motor nerve conduction velocity (MNCV) in the forearm. Both MNCV in the forearm and EMNAP can indicate retrograde degeneration in CTS, but the MNCV cannot be measured when muscle atrophy is severe and the CMAP cannot be elicited. Therefore, we believe that EMNAP is a more useful measure of the retrograde changes in CTS. PMID- 8436087 TI - A comparison of close proximity concentric and modified single fiber electromyographic recordings from extensor digitorum communis. AB - Using a combined concentric (CN) and modified single fiber (MSF) electromyography (EMG) needle electrode with both recording surfaces at the tip approximately 25 microns apart, 30 motor unit action potentials (MUAP) were recorded from one extensor digitorum communis (EDC) muscle, triggering from the CN and averaging both the CN and MSF recordings. Correlations of MUAP amplitude (r = 0.767), number of turns (r = 0.839), and number of negative-going-positive-going turn (NT) (r = 0.737) between the CN and MSF recordings were statistically significant (p < 0.001). For NTs common to both recordings, correlations of rise time (r = 0.866), amplitude (r = 0.816), and interpeak interval (IPI) (r = 0.999) were statistically significant (p < 0.001). Mean +/- SD single fiber potentials (SFP), approximate SFP with rise times less than 500 microseconds, and NTs for the MSF recordings and NTs for the CN recordings were 0.73 +/- 0.69, 1.20 +/- 0.48, 1.83 +/- 0.87, and 1.93 +/- 0.78, respectively. This study supports evidence that one or a few SFP contribute to the spike component of the MUAP. PMID- 8436088 TI - Severe vitamin A deficiency in a rural village in the Hararge region of Ethiopia. AB - A total of 240 children were examined for vitamin A deficiency in a village in Hararge region of Ethiopia. Night blindness, Bitot's spots, corneal xerosis, corneal ulceration and corneal scars were observed in 69, 16, 2, 15 and 14 children, respectively, based on the most severe eye signs. Blood was collected from 76 children with eye signs and 9 other children selected at random. The concentration of retinol (vitamin A) in serum was < 0.35 mumol/l in 30.2% of children and the median serum retinol-binding protein, iron, transferrin saturation and ferritin levels were low while the parameters of iodine status, total triiodothyronine, total thyroxine and thyrotropin, were all within the normal range. Levels of IgG and IgM were elevated in 78.8% and 82.4% children, respectively, while C-reactive protein levels were elevated in 42.4% of children. There was a higher prevalence of wasting (33%) than stunting (10%) with an additional 8% of children being both stunted and wasted. In the 2 years prior to the study, there were 74 deaths of which 17 were reported to be associated with ruptured corneas. The community had been dependent on relief food aid for the previous 6 years. PMID- 8436089 TI - Validating a simplified approach to the dietary assessment of vitamin A intake in preschool children. AB - The International Vitamin A Consultative Group (IVACG) developed guidelines for a simplified dietary assessment to identify groups at risk to an inadequate intake of vitamin A. This study was conducted in Bangladesh to validate this simplified approach. The individual food intakes of 121 children, aged 2-5 years, were measured in a two-round weighted household dietary survey for three consecutive days in 112 households in two ecologically different locations. On each next day following the day of weighed dietary survey the simplified questionnaire designed to estimate the preschool child's intake of food sources of vitamin A was administered. The intake of food sources of vitamin A obtained by the two methods was converted both into equivalent units and into consumption index (CI) scores for comparison. There was a very strong agreement between the CI scores obtained by the two methods. Although matched paired tests showed some difference between the mean CIs obtained by the two methods, as far as the identification of children at high risk is concerned (which is the objective of the simplified assessment) there was no marked difference between the two methods. The study revealed that the simplified method can fairly predict the vitamin A intake of preschool children and thus can be regarded as a useful tool for identifying groups at risk to inadequate intake of vitamin A. Large seasonal variations in the habitual intake pattern of vitamin A confirm the necessity of obtaining information on the usual consumption patterns of seasonally available food sources of vitamin A, in addition to the 24-h intake estimates. PMID- 8436090 TI - Effects of cod liver oil on lipids and platelets in males and females. AB - Thirty-four healthy non-smoking subjects (20 men and 14 women) were given 25 ml cod liver oil (CLO) daily as dietary supplement for 8 weeks in a controlled cross over study. Prior to intervention, women had significantly higher serum total (P < 0.05) and high density lipoprotein (HDL) (P < 0.001) cholesterol values, higher platelet counts (P < 0.05) and lower thromboxane B2 (TxB2) generation (P < 0.01) in response to collagen stimulation in platelet-rich plasma (PRP) than men. Before intervention, no gender differences in platelet aggregation were observed. Following CLO intervention, serum triglycerides were reduced by 0.21 +/- 0.09 mmol/l (P < 0.05) in men. LDL cholesterol increased in men by 0.28 +/- 0.12 mmol/l (P < 0.05), while the values in women decreased insignificantly. The response in LDL cholesterol to CLO supplementation differed significantly between genders (P < 0.05). HDL cholesterol was not altered in any group. Mean platelet volume (MPV) increased by approximately 6% in both sexes (P < 0.01). After CLO intake, platelet sensitivity to collagen in PRP decreased in men only (P < 0.01), and the response was significantly different from that in women (P < 0.05). Thromboxane B2 generation following platelet aggregation in PRP was equally decreased by CLO. Our findings indicate sex differences in the response to CLO regarding LDL cholesterol and platelet sensitivity to collagen in PRP. PMID- 8436091 TI - Fatty acid composition of serum phosphatidylcholine in healthy subjects consuming varying amounts of fish. AB - Fatty acid composition of serum phosphatidylcholine was studied in subjects living in the same area and selected for high consumption of fat fish, high consumption of lean fish, moderate or no consumption of fish. The proportion of eicosapentaenoic acid (20:5) in serum phosphatidylcholine was fourfold higher, and that of docosahexaenoic acid (22:6) twofold higher among high consumers of fish compared to non-consumers, and these proportions were also higher in fat fish consumers than in high consumers of lean fish, and in moderate consumers compared to non-consumers. In the whole group the intake of fat fish was correlated to the proportions of 20:5, 22:6 and total n-3 fatty acids in serum phosphatidylcholine. The estimated intake of total n-3 fatty acids from fish was highly correlated to the proportions of these fatty acids in serum phosphatidylcholine (r = 0.87). Plasma triglyceride concentration was lower among high fat fish consumers than in other groups, but no differences between groups were observed for concentration of cholesterol, LDL cholesterol, and HDL cholesterol. It is concluded that subjects who consume high amounts of fat fish in their normal diet attain approximately the same proportions of n-3 fatty acids in serum phosphatidylcholine as reported for subjects taking fish oil supplements, and that fatty acid composition of serum lipids can be used as a marker of intake of fat fish. PMID- 8436092 TI - Associations of serum lipids with metabolic control and diet in young subjects with insulin-dependent diabetes mellitus in Finland. AB - Association of serum lipids with metabolic control and diet were studied in 72 young subjects with insulin-dependent diabetes mellitus (IDDM). Data on food consumption were collected by the 48-h recall method. Glycosylated haemoglobin (Hb) A1 was used as a measure of metabolic control. There were no differences between males and females in the mean values for serum total cholesterol (TC, 4.5 and 4.9 mmol/l, respectively), low density lipoprotein cholesterol (LDL-C, 2.7 and 3.0 mmol/l), high density lipoprotein cholesterol (HDL-C, 1.3 and 1.4 mmol/l), or serum triglycerides (TG, 1.1 and 1.0 mmol/l). Diabetic subjects who were in better metabolic control (HbA1 < 10.5%), when compared with those in poorer control (HbA1 > or = 10.5%) had lower TC and TG values and a higher HDL C/TC ratio. HbA1 level and intake of saturated fatty acids were positively associated with serum TC and LDL-C values and explained 14% and 15% of the variation in TC and LDL-C, respectively. HbA1 level and insulin dose per kg of body weight were positively associated with serum TG values and explained 30% of the variation in TG. Serum TC and LDL-C levels of young subjects with IDDM could be lowered by improving their metabolic control and decreasing their saturated fatty acid intake. PMID- 8436093 TI - Acute myeloid leukaemia and retinoids. PMID- 8436094 TI - Impact of large-dose vitamin A supplementation on childhood diarrhoea, respiratory disease and growth. AB - One hundred and seventy-two 0.5-3.0-year-old children in a mountainous area of northern Hebei Province of China were randomly assigned to a vitamin A supplementation group (n = 98) or a control group (n = 74) for a 1 year double blind study. Capsules containing 200,000 IU vitamin A and 40 IU vitamin E were given to the children in the experimental group 3 and 9 months after baseline examination. During the 12 month study period, there was a significant reduction in the incidence of diarrhoea (P < 0.01) and respiratory disease (P < 0.01) in the children of the experimental group compared to the control. Risk of diarrhoea and respiratory disease were respectively 2.5 and 3.4 times higher in the control children. Serum retinol and IgA levels of the treatment group were significantly higher than that of control group (P < 0.01) 7 weeks after first supplementation. There was no significant difference in saliva IgA level between groups. No significant differences in growth were observed. It was concluded that supplementation with large doses of vitamin A decreased the incidence and severity of diarrhoea and respiratory disease in these children, possibly through enhanced activity of the immune system, but had no effect on growth over 1 year. PMID- 8436095 TI - The influence of consuming fatty fish instead of red meat on plasma levels of vitamins A, C and E. AB - The effect of fatty fish consumption on the plasma levels of vitamins A, C and E and the intake of these vitamins were studied in 12 males and 16 females with a mean age of 32.4 years. This cross-over study had a 3 week baseline, 6 week experimental and 6 week post-experimental period with a washout period of approximately 3 months in between. Four 7 day dietary records were used to collect dietary information. Blood samples were drawn after an overnight fast at baseline and every third week thereafter. Plasma total cholesterol, high density lipoprotein cholesterol, triacylglycerol, vitamin A, C and E levels were determined. During the experimental periods red meat was consumed by half of the volunteers while fatty fish was consumed by the other half. Diets were crossed over after the washout period. Plasma levels of vitamins A, C and E remained within normal limits in the experimental periods. The intake of polyunsaturated fatty acids (PUFA) was significantly higher in the experimental fatty fish period than in the experimental red meat period. The dietary ratio of vitamin E: PUFA and the plasma vitamin E level were lower (P < 0.01) in the experimental fatty fish period than in the experimental red meat period but the ratio of plasma vitamin E: total cholesterol plus triacylglycerol did not differ between the experimental periods. In this study none of the experimental groups were at risk in terms of their intake of the antioxidant vitamins. PMID- 8436096 TI - Experience in thyroid scintigraphy with Ethiopian patients. AB - One thousand and thirty-seven thyroid scintigraphy examinations done in the Nuclear Medicine Unit of Tikur Anbessa Hospital, Addis Abeba, Ethiopia between December 1984 and September 1989 were analyzed to assess their diagnostic value. Thirty-one percent of the referrals were to investigate clinically detectable solitary nodules, and of these fifty-six percent had "cold" nodules and twenty three percent "hot" nodules. Fifty-five percent of the referrals for evaluation of goitre were for multinodular goitres and twelve percent for diffuse. Thirteen of fifty-three cases with suspected ectopic thyroid tissue were positive. Little useful information was obtained in the evaluation of goitre. It is concluded that thyroid scintigraphy was an unnecessary investigation in the evaluation of goitres in euthyroid patients. Its primary role was in the investigation of the solitary nodule, ectopic thyroid tissue and the retrosternal goitre. Therefore, only selected patients should be investigated with thyroid scintigraphy. PMID- 8436097 TI - The epidemiology of lathyrism in north and central Ethiopia. AB - Lathyrism is a neurotoxic disorder caused by excessive, prolonged consumption of the hardy, environmentally tolerant legume, the grass-pea, Lathyrus sativus, which contains the neurotoxic amino acid beta-N-oxalylamino-L-alanine acid (BOAA). The disease develops after heavy consumption of grass-pea for over two months. It is uniformly manifested by a predominantly motor spastic paraparesis with varying degrees of disability. A door-to-door epidemiological survey for the disease using trained lay health workers was carried out in the major areas of northwest and central Ethiopia where L. sativus is grown. For security reasons, some of the other endemic areas wre not accessible for the survey. The survey involved a population of 1,011,272. A total of 3,026 affected persons were identified. The disease was found to be widespread in the northwest and central highland areas of the country. The prevalence rates ranged from 1/10,000 to 7.5/1,000. The highest prevalences were in North and South Gonder, and East and West Gojam. The male:female ratio of cases was 2.6:1; the females exhibited a milder form of the disease. The cultivation of L. sativus is increasing in Ethiopia, which makes the development of low-BOAA strains very important in order to control the high incidence of lathyrism, a crippling disease which affects the productive young members of the society. PMID- 8436098 TI - The pattern of thyroid diseases in adult Ethiopians and experience in management. AB - During the study period, between February 1986 and July 1991, a total of 373 thyroid patients (68.3% of the total endocrine cases) were seen in the weekly endocrine referral clinic of Tikur Anbessa Hospital (TAH); 258 (69.2%) came from Addis Abeba, 41 were males and 332 females (M:F = 1:8.1) and 71.9% were below 40 years of age. Thyrotoxicosis was seen in 43.7% of the patients, followed by euthyroid solitary nodules (23.6%) and simple goitres (22.3%). Euthyroid multinodular goitre was seen in 6.7% while hypothyroidism and thyroiditis were less frequent. Graves' disease was the main cause (41.7%) of thyrotoxicosis, followed by toxic multinodular goitre TMNG (31.9%), toxic solitary nodule (22.1%), Jodbasedow phenomenon (3.1%) and thyroiditis (1.2%). All thyrotoxic patients responded to the treatment, but 4 of 21 Graves' cases with relative triiodothyronine (T3) elevation relapsed after treatment was discontinued. Nine thyrotoxic patients had surgery after euthyroid state was attained; 1 each became hypothyroid and hyperthyroid a year later, 6 remained euthyroid and 1 did not return. Fine needle aspiration biopsy (FNAB) was helpful both as a diagnostic and therapeutic tool. Of 42 cystic nodules, 30 were repeatedly aspirated; 6 were cured and the rest had a reduction in size by 50%. Nine cases of solitary nodule, 3 cystic and 6 solid, were operated and the histology confirmed the cytology diagnosis in all but 1; in that one case, the cytology showed a benign lesion while the histology revealed papillary carcinoma. PMID- 8436099 TI - Comparison of immunodiagnosis (ELISA) and stool examination (Kato technique) in the diagnosis of Schistosoma mansoni in Ethiopia. AB - Schistosoma mansoni tegument antigen, extracted with 3M KCl, was employed to detect total antibodies due to the parasite in sera from 559 people living in endemic and nonendemic areas in Ethiopia. Cut-off point for positive and negative ELISA values was defined based on sera from the nonendemic area and results were compared with results of stool examination (Kato's thick smear technique). S. mansoni prevalence was 53.0% and 51.2% by ELISA and Kato, respectively. The ELISA system detected Schistosoma antibodies in 99.0% of the parasitologically positive individuals and in 4.8% and 12.5% of the negative ones from endemic and nonendemic areas, respectively. The sensitivity and specificity of ELISA test was 99.0% and 87.5%, respectively. The false positive reactions appear to be related to the presence of other parasites. The peak intensity of infection, as measured by both ELISA and Kato, was at 14 years of age and infection appears to be more prevalent in males than females. No relationship was established between intensity of infection and ELISA results. The use of the ELISA system in the diagnosis of S. mansoni in Ethiopia is discussed. PMID- 8436100 TI - Bone and joint tuberculosis in childhood in a children's hospital, Addis Abeba. AB - The records of children admitted to the Ethio-Swedish Children's Hospital with the diagnosis of bone and/or joint tuberculosis (TB) between 1985 and 1990 were reviewed. There were 41 patients: 25 (61%) males and 16 (39%) females. The diagnosis was based on history, clinical and radiologic findings supported by a positive PPD reaction and elevated erythrocyte sedimentation rate (ESR). A high index of suspicion based on epidemiologic considerations was also important. Whereas in ambulatory patients the commonest site of bone involvement was the spine, in this series of hospitalized patients the most common site of skeletal TB was the hip joint (22 patients) compared to spinal involvement (14 patients) suggesting the more incapacitating and crippling nature of hip joint disease. In the remaining 5 patients, the knee (1), the ankle (1) a metatarsal (2) or a phalanx (1) were involved. The period of hospital stay ranged from 3 to 180 days, with a mean of 56. Mean hospital stay was much longer for patients with TB arthritis of the hip joint than for those with spondylitis, 71 and 43 days respectively. The need for early diagnosis and treatment aiming at full restoration of function of the involved joint is emphasized. In TB spondylitis, early diagnosis and treatment should aim to minimize deformity and prevent paraplegia. PMID- 8436101 TI - Epidemic meningococcal meningitis in children. A retrospective analysis of cases admitted to ESCH (1988). AB - One hundred twenty four cases of meningococcal meningitis were seen at the Ethio Swedish Children's Hospital (ESCH) during the epidemic period December 1, 1987 to January 31, 1989. Data on demographic and clinical profile of patients were collected and analyzed. Two thirds of patients were above 5 years of age. Fifty percent of the patients came from the "mercato area" of the city of Addis Abeba, Higher 3, 4, 5 & 6. Thirteen cases were from outside Addis Abeba. The main clinical presentations were fever and vomiting in all age groups and headache in those above 5 years of age. The classical meningeal signs were rare in those below 5 years of age. The most common neurological deficit was loss of hearing. Mortality was very low (only 3 deaths). Continuous surveillance of demographic and clinical indicators is recommended as they could be useful early warning signs of an epidemic. PMID- 8436102 TI - Advances in metallo-procarboxypeptidases. Emerging details on the inhibition mechanism and on the activation process. AB - Our knowledge on the structure and functionality of pancreatic carboxypeptidases is rapidly expanding to include that of their zymogen forms. The recent application of fast and mild isolation procedures, together with modern molecular genetic and biochemical-biophysical characterization approaches, has provided a clearer view of the basic structures and functional states in which these zymogens occur, and their evolutionary relationships. The same holds for related metallo-carboxypeptidases, either in the pro or active forms, that have been isolated and characterized in non-digestive fluids and tissues, where they probably play an important role in protein and peptide processing. The determination of the three-dimensional structure of the A and B pancreatic zymogens has revealed the molecular determinants of their inactivity and proteolytic activation. The folding of their 95-residue activation segment in a globular N-terminal domain (74-81 residues) and in a connecting region (20-14 residues), and the specific contacts of these pieces with the substrate binding sites of the enzyme, are important factors in zymogen inhibition. On the other hand, the different length of the alpha-helical connecting region and the stability of its contacts with the enzyme account for the different activation properties of A and B zymogens. PMID- 8436103 TI - Lignin peroxidase L3 from Phlebia radiata. Pre-steady-state and steady-state studies with veratryl alcohol and a non-phenolic lignin model compound 1-(3,4 dimethoxyphenyl)-2-(2-methoxyphenoxy)propane-1,3-diol. AB - The catalytic cycle of lignin peroxidase (LiP, ligninase) isozyme L3 from the white-rot fungus Phlebia radiata was investigated using stopped-flow techniques. Veratryl (3,4-dimethoxybenzyl) alcohol and a lignin model compound, non-phenolic beta-O-4 dimer 1-(3,4-dimethoxyphenyl)-2-(2-methoxyphenoxy)propane-1,3-diol, were used as electron donors. This is the first report on the detailed kinetic analysis of a LiP-catalysed C alpha-C beta bond cleavage of the dimer, representing the major depolymerisation reaction in the lignin polymer. The native enzyme showed a typical heme peroxidase absorbance spectrum with a Soret maximum at 407 nm. Following the reaction with H2O2, the Soret band decreased in absorbance, shifted to 403 nm and then to 421 nm, demonstrating the formation of compound I followed by the formation of compound II, respectively. Similar results have been reported for the LiP from Phanerochaete chrysosporium upon reaction with H2O2. However, compound I of L3 was more stable in the absence of additional electron donors. The second-order rate constant of compound I formation by H2O2 was determined to be 6 x 10(5) M-1 s-1 and was the same at pH 3.0 and 6.0. Compound I was rapidly reduced to compound II and further to native enzyme when either veratryl alcohol or the beta-O-4 dimer was supplied as electron donor and in both cases veratraldehyde appeared as the major product. At pH 6.0, the second-order rate constant for compound II formation was similar with either veratryl alcohol or the beta-O-4 dimer (6.7 x 10(3) and 6.5 x 10(3) M-1 s 1, respectively). At pH 3.0 formation of compound II with either reductant proceeded so rapidly that determination of the respective rate constants was not possible. The results point to identical catalytic cycles of L3 with veratryl alcohol or the beta-O-4 dimer involving both compounds I and II as intermediates and participation of the same veratryl alcohol radical as the most appropriate reductant for compound II. Chemical evidence of such a radical, formed after the initial LiP-catalysed one-electron oxidation of beta-O-4 dimeric lignin models, is presented in a separate article [Lundell, T., Schoemaker, H., Hatakka, A. & Brunow, G. (1993) Holzforschung, in the press]. The catalytic redox-cycle and the oxidation mechanism presented here reconcile seemingly contradictory results obtained in previous studies on LiP kinetics during the last decade. PMID- 8436104 TI - DNA excision-repair synthesis is enhanced in a murine leukemia L1210 cell line resistant to cisplatin. AB - Among various molecular mechanisms of cell resistance to antitumor agents such as cisplatin, it has recently been suggested that enhanced DNA-repair activity might be involved in the resistant phenotype of cell lines. Mouse leukemia-cisplatin resistant cell lines L1210/10 (adapted in vitro) and L1210/DDP (adapted in vivo) have been reported to exhibit an increase DNA-repair activity, as determined by host-cell reactivation after transformation with damaged plasmids. In this paper, excision-repair activity was monitored by an in-vitro assay allowing quantification of DNA-repair synthesis in cell extracts from resistant and sensitive parental cells (L1210/10 versus L1210/0 and L1210/DDP versus L1210/S). Experimental conditions for optimal repair-synthesis activity were found to be different from these reported with human cell-line extracts. L1210/S sensitive cell line, grown in vivo by a weekly intraperitoneal graft in mice, displayed a repair activity about fourfold lower than the same cell line maintained in vitro or than L1210/0 cell grown in vitro. The repair activity was found similar in a L1210/10 and L1210/0 cell lines, but it was enhanced in L1210/DDP resistant cell line when compared with its parental line. PMID- 8436105 TI - The amino acid sequence of glutathione transferase from Proteus mirabilis, a prototype of a new class of enzymes. AB - The complete amino acid sequence of glutathione transferase from Proteus mirabilis was determined. The sequence was reconstructed by analysis of peptides obtained after cleavage by trypsin, Glu-C and Asp-N endoproteinases. The enzyme subunit is composed of 203 amino acid residues corresponding to a molecular mass of 22856 Da. Comparison of this sequence with other known primary structures of the corresponding enzyme from different sources shows a low level of identity (17 26%) with only seven conserved residues in all the sequences considered. This novel glutathione transferase could represent the prototype of a new class, possibly including other bacterial enzymes. PMID- 8436106 TI - Changes in the insulin-sensitive glycosyl-phosphatidyl-inositol signalling system with aging in rat hepatocytes. AB - An inositol-phosphate glycan (InsP glycan), which is the polar head group of an insulin-sensitive glycosyl-phosphatidylinositol (glycosyl-PtdIns), has been reported to mimic some insulin actions when added to different types of cells. In connection with this, a specific, time-dependent and energy-dependent transport system for this InsP glycan has been identified in isolated rat hepatocytes [Alvarez, J. F., Sanchez-Arias, J. A., Guadano, A., Estevez, F., Varela, I., Feliu, J. E. & Mato, J.M. (1991) Biochem. J. 274, 369-374]. Here we have investigated the glycosyl-PtdIns-dependent insulin-signalling system in hepatocytes isolated from either 3-month-old or 24-month-old rats. Aging reduced the stimulatory effect of insulin on [U-14C]glucose incorporation into glycogen, caused a significant decrease in basal glycosyl-PtdIns levels and blocked the insulin-mediated hydrolysis of this lipid. In 24-month-old rats, we also observed a diminution in the rate of hepatocyte InsP-glycan uptake and a marked reduction of the stimulatory effect of this compound on glycogen synthesis. These results support the hypothesis that insulin resistance associated with aging is accompanied by an impairment of the glycosyl-PtdIns-dependent cellular signalling system. PMID- 8436107 TI - Hydroperoxide metabolism in rat liver. K+ channel activation, cell volume changes and eicosanoid formation. AB - Addition of t-butylhydroperoxide (0.2 mM) to isolated perfused rat liver led to a net K+ release of 7.2 +/- 0.2 mumol/g within 8 min and a net K+ reuptake of 6.6 +/- 0.4 mumol/g following withdrawal of the hydroperoxide, in line with earlier findings by Sies et al. [Sies, H., Gerstenecker, C., Summer, K. H., Menzel, H. & Flohe, R. (1974) in Glutathione (Flohe, L., Benohr, C., Sies, H., Waller, H. D., eds) pp. 261-276, G. Thieme Publ. Stuttgart]. Net K+ release roughly paralleled the amount of GSSG released from the liver under the influence of the hydroperoxide. The t-butylhydroperoxide-induced K+ efflux was inhibited by approximately 70% in the presence of Ba2+ (1 mM), by 30% in Ca(2+)-free perfusions and was decreased by 50-60% when the intracellular Ca2+ stores were simultaneously depleted by repeated additions of phenylephrine. t Butylhydroperoxide-induced K+ efflux was accompanied by a decrease of the intracellular water space by 58 +/- 14 microliter/g (n = 4), corresponding to a 10% cell shrinkage. The effect of t-butylhydroperoxide on cell volume was inhibited by 70-80% in the presence of Ba2+. In isolated rat hepatocytes treatment with t-butylhydroperoxide led to a slight hyperpolarization of the membrane at concentrations of 100 nM, but marked hyperpolarization occurred at t butylhydroperoxide concentrations above 10 microM. t-Butylhydroperoxide (0.2 mM) transiently increased the portal-perfusion pressure by 3.3 +/- 0.6 cm H2O (n = 18), due to a slight stimulation of prostaglandin-D2 release under the influence of the hydroperoxide. In the presence of Ba2+ (1 mM), t-butylhydroperoxide increased the perfusion pressure by 12.7 +/- 1.2 cm H2O (n = 9) and produced an approximately tenfold increase of prostaglandin-D2 and thromboxane-B2 release. Under these conditions, glucose output from the liver rose from 0.9 +/- 0.03 to 2.9 +/- 0.7 mumol.g-1.min-1 (n = 4) with a time course roughly resembling that of portal-pressure increase and prostaglandin-D2 overflow. These effects were largely abolished in the presence of ibuprofen or the thromboxane-receptor antagonist BM 13.177. The t-butylhydroperoxide effects on perfusion pressure, glucose and eicosanoid output were also enhanced in the presence of insulin or during hypotonic exposure; i.e. conditions known to swell hepatocytes, but not during hyperosmotic exposure. The data suggest that t-butylhydroperoxide induces liver-cell shrinkage and hyperpolarization of the plasma membrane due to activation of Ba(2+)-sensitive K+ channels.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8436108 TI - On the mechanism of energy transfer to Tb3+ ions in proteins. A time-resolved luminescence study of the Tb-elastase complex. AB - Intraprotein energy transfer to terbium ions is widely used for probing distances of calcium sites in proteins. In this work we have performed a time-resolved study of the sensitized luminescence in elastase using a pulsed laser excitation at 265 nm. Terbium-sensitized luminescence was found to build-up within about 150 microseconds, which indicates that the protein transfers energy at a rate several orders of magnitude slower than expected for a singlet state donor. From the rise time of the signal and from its variation with the oxygen concentration, it can be deduced that 80% of the transfer originates from the first triplet excited state of one unique aromatic residue. From the comparison of protein fluorescence and sensitized terbium luminescence excitation spectra the sensitizer was identified as a tryptophan, presumably Trp141, which is situated only 0.7-0.9 nm away from the Tb site. The results are at variance with the usual assumption that energy is transferred from the first excited singlet state of aromatic residues according to a long-range dipole-dipole interaction and are more consistent with a short-distance exchange mechanism. PMID- 8436109 TI - Mutant aspartate aminotransferase (K258H) without pyridoxal-5'-phosphate-binding lysine residue. Structural and catalytic properties. AB - If the pyridoxal-phosphate-binding lysine residue 258 of aspartate aminotransferase is exchanged for a histidine residue, the enzyme retains partial catalytic competence [Ziak, M., Jaussi, R., Gehring, H. and Christen, P. (1990) Eur. J. Biochem. 187, 329-333]. The three-dimensional structures of the mutant enzymes of both chicken mitochondria and Escherichia coli were determined at high resolution. The folding patterns of the polypeptide chains proved to be identical to those of the wild-type enzymes, small conformational differences being restricted to parts of the active site. If aspartate or glutamate was added to the pyridoxal form of the mutant enzyme [lambda max 392 nm and 330 nm (weak); negative CD at 420 nm, positive CD at 370 nm and 330 nm], the external aldimine (lambda max = 430 nm; negative CD at 360 nm and 430 nm) transiently accumulated. Upon addition of 2-oxoglutarate to the pyridoxamine form (lambda max 330 nm, positive CD), a putative ketamine intermediate could be detected; however, with oxalacetate, an equilibrium between external aldimine and the pyridoxal form, which was strongly in favour of the former, was established within seconds. The transamination cycle with glutamate and oxalacetate proceeds only three orders of magnitude more slowly than the overall reaction of the wild-type enzyme. The specific activity of the mutant enzyme is 0.1 U/mg at 25 degrees C and constant from pH 6.0 to 8.5. Reconstitution of the mutant apoenzyme with [4' 3H]pyridoxamine 5'-phosphate resulted in rapid release of 3H with a first-order rate constant kappa' = 5 x 10(-4) s-1 similar to that of the wild-type enzyme. Apparently, in aspartate aminotransferase, histidine can to some extent substitute for the active-site lysine residue. The imidazole ring of H258, however, seems too distant from C alpha and C4' to act efficiently as proton donor/acceptor in the aldimine-ketamine tautomerization, suggesting that the prototropic shift might be mediated by an intervening water molecule. Transmination of the internal to the external aldimine apparently can be replaced by de novo formation of the latter, and by its hydrolysis in the reverse direction. PMID- 8436110 TI - Isolation and structural characterization of novel sialylated oligosaccharide alditols from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis. AB - The carbohydrate chains of the respiratory-mucus glycoproteins of a patient (blood group O) suffering from bronchiectasis due to Kartagener's syndrome, were released by alkaline borohydride treatment of a pronase digest. The structures of 82 neutral and low-molecular-mass sialylated oligosaccharides have been described previously [van Kuik A., de Waard P., Vliegenthart J. F. G., Klein A., Carnoy C., Lamblin G. Roussel P. (1991) Eur. J. Biochem. 198, 169-182]. In the present work, medium-size sialylated oligosaccharides were obtained after ion-exchange chromatography and were subsequently separated into 36 fractions utilizing gel filtration, HPLC on normal-phase alkylamine-bonded silica and reverse-phase HPLC. From these fractions, the following six sialylated hepta- and octa-saccharide alditols have been characterized by employing 500-MHz 1H-NMR spectroscopy, in conjunction with fast-atom-bombardment mass spectroscopy and methylation analysis. [formula: see text] PMID- 8436111 TI - Expression of the gamma-subunit gene of desulfoviridin-type dissimilatory sulfite reductase and of the alpha- and beta-subunit genes is not coordinately regulated. AB - It has been shown [Pierik, A. J., Duyvis, M. G., van Helvoort, J. M. L. M., Wolbert, R. B. G. & Hagen, W. R. (1992) Eur. J. Biochem. 205, 111-115] that desulfoviridin, the dissimilatory sulfite reductase of sulfate-reducing bacteria of the genus Desulfovibrio, contains a third, gamma, subunit (11 kDa), in addition to the well-established alpha (50 kDa) and beta (40 kDa) subunits, and an alpha 2 beta 2 gamma 2 subunit structure has been proposed. Cloning and sequencing of the dsvC gene indicated it to encode a protein of 105 amino acids (11.9 kDa; gamma subunit). The finding that the dsvC gene, located on a 3.5-kb SacII fragment, is transcribed in both Escherichia coli and Desulfovibrio vulgaris as an mRNA of only 400-600 nucleotides, and that both the dsvA and dsvB genes are present on a 7.2-kb SacII fragment, indicates that dsvC forms a separate transcriptional unit. The steady-state level of alpha and beta subunits expressed in D. vulgaris Hildenborough cells is rather constant, while that of the gamma subunit increased strongly in the stationary growth phase. Biochemical analysis of the purified protein, expressed in E. coli, and library comparison of its sequence, have so far failed to establish the function of gamma. PMID- 8436112 TI - Localization and functional analysis of DNase-I-hypersensitive sites in the human c-sis/PDGF-B gene transcription unit and its flanking regions. AB - We studied the regulation of the expression of the human c-sis/PDGF-B gene in the following panel of cell lines: K562 cells, in which expression is inducible by phorbol esters; cytotrophoblast-derived cell lines JEG-3 and JAR; carcinoma derived cell lines PC3, T24 and HeLa, which show extensive differences in c-sis mRNA content; dermal fibroblasts, which do not express the gene. We demonstrate that the wide variety of levels of c-sis mRNA in these cells is mainly determined at the transcription level. Extensive gene rearrangements or amplifications, or significant differences in the stability of the c-sis transcript could not be found. In fibroblasts and placenta cell lines, inaccessibility of the c-sis promoter, rather than the absence of transcription factors that activate it, inhibits expression of the endogenous gene. Examination of the chromatin structure of the transcription unit and immediate flanking regions revealed several cell-type-specific DNase-I-hypersensitivity (DH) sites. Functional analysis of genomic fragments harbouring one or more DH sites showed the presence of negative regulatory elements within intron 1, and of an activating element downstream of the gene. A DH site, located immediately downstream of the promoter in dermal fibroblasts, may regulate accessibility of the promoter by means of specific nucleosome phasing. PMID- 8436113 TI - Use of gene fusions of the structural gene sdaA to purify L-serine deaminase 1 from Escherichia coli K-12. AB - The purification by affinity chromatography of beta-galactosidase from strains carrying sdaA/lacZ gene fusions results in the copurification of L-serine deaminase 1. We conclude that sdaA is the structural gene for the latter enzyme. The purified L-serine deaminase 1 obtained after collagenase treatment of an sdaA collagen-lacZ fusion differs from the native enzyme by the addition of several amino acids at the C-terminal. Like the enzyme in crude extracts, this purified enzyme is catalytically inactive, and is activated by incubation with iron and dithiothreitol. PMID- 8436114 TI - Immunochemical characterisation of a dehydroepiandrosterone sulfotransferase in rats and humans. AB - A member of the rat liver hydroxysteroid sulfotransferase (ST) enzyme family metabolising dehydroepiandrosterone (DHEA) was purified from female rats and used to raise rabbit polyclonal antibodies. Characterisation of this antibody preparation demonstrated that it was specific for DHEA ST, and recognised a single 30-kDa protein on immunoblot analysis of rat liver cytosol which was expressed preferentially in female rat liver, and immunohistochemical localisation of the protein in female rat liver determined that DHEA ST was distributed homogeneously in the cytoplasm of hepatocytes. Examination of the extrahepatic expression of this protein showed it to be located predominantly in the liver, although a small amount of enzyme activity was found in the kidney which was not apparently subject to the same sex difference as the hepatic activity. Immunological analysis suggested that this activity was not due to the action of DHEA ST, but to another, unidentified ST isozyme. The antibody cross reacted strongly with adult human liver DHEA ST, recognising a protein of 35 kDa on immunoblotting. Using this antibody preparation, the distribution of DHEA ST in mid-trimester human fetal tissues was examined, and it was shown that the enzyme is expressed in the adrenal and liver, but not to any significant extent in the kidney or lung. This antibody therefore provides a powerful tool for investigating the function of DHEA ST. PMID- 8436115 TI - Cloning, sequencing and expression of the gene encoding glucose dehydrogenase from the thermophilic archaeon Thermoplasma acidophilum. AB - The gene encoding glucose dehydrogenase has been identified by Southern analysis of doubly restricted genomic Thermoplasma acidophilum DNA, using two redundant 17 residue oligonucleotide probes reverse translated from protein N-terminal sequence data. A 1670-bp BamH1-EcoR1 restriction fragment was ligated into pUC19 and pUC18 (constructs pTaGDH1 and pTaGDH2, respectively) and cloned in Escherichia coli. The sequence of the whole fragment was determined, and a 1059 bp open reading frame identified as the gene encoding glucose dehydrogenase. Cell free extracts from E. coli carrying construct pTaGDH1 displayed glucose dehydrogenase activity indistinguishable from controls, but extracts from cells carrying pTaGDH2 displayed a 600-fold increase in glucose dehydrogenase activity. For high-level expression and purification of native protein, the glucose dehydrogenase coding sequence was subcloned into pMEX8. Glucose dehydrogenase purified from E. coli expressing the pMEX8 construct was indistinguishable by SDS/PAGE, N-terminal amino-acid sequence and kinetic analysis from the native enzyme purified from Tp. acidophilum. The derived 352-amino-acid sequence shows less than 20% identity with the glucose dehydrogenases of Bacillus subtilis and Bacillus megaterium but, by comparison with other eubacterial and eukaryotic dehydrogenase sequences, a portion of its sequence has been tentatively identified as a cofactor-binding region. PMID- 8436116 TI - CD and 1H-NMR studies on the conformational properties of peptide fragments from the C-terminal domain of thermolysin. AB - The propensity of the peptide fragments 233-248, 245-260, 258-276, 279-298 and 299-316 from the thermolysin C-terminal domain to form non-random structures has been examined by CD and two-dimensional NMR spectroscopy. The conformational properties of these fragments have been studied in aqueous solution and in the mixed solvent trifluoroethanol/H2O (3:7 by vol.). Small but detectable populations of helical structures (up to 10-20%) in aqueous solution have been found for the fragments 233-248, 279-298 and 299-316. These populations are remarkably enhanced (50-70%) in the more hydrophobic mixed solvent, where the fragment 258-276 also forms a comparable helical population. These four fragments are helical in the native crystal structure and the spanning of the corresponding helices in the isolated peptides in solution matches very closely the ones in the native structure. In contrast, the fragment 245-260, an omega-loop in the crystal, remains unstructured in both solvents. Medium-range NOE between protons in sidechains indicate the adoption of preferred sidechain conformations accompanying helix formation. Results are in agreement with the framework model of folding, in which native elements of secondary structure are formed first and folding follows from the collapse of these structural elements. PMID- 8436117 TI - Interleukin-1 beta-specific partial agonists defined by site-directed mutagenesis studies. AB - Monocyte-derived interleukin 1 (IL-1) mediates a wide range of biological effects including destruction of the cartilage matrix in articular diseases such as rheumatoid and osteoarthritis. To elucidate further the relationships between protein structure and biological activities, we have analyzed the sequence of several IL-1 polypeptides using the algorithm of Parker, the hydrophobic cluster analysis method and published structural data. This led us to identify several residues that seemed to be strictly topologically conserved, with respect to identifiable secondary structures features, although this was not readily apparent from sequence alignments. We performed site-directed mutagenesis on some of these conserved residues, as well as on those predicted to occur in external loops of the polypeptide. Human IL-1 beta mutant polypeptides were expressed in Escherichia coli in soluble form and purified to homogeneity by anion-exchange and gel-filtration chromatography. Their biological effects (binding to EL4-6.1 murine thymocytes, Raji human B cells and rabbit chondrocytes cells, lymphocyte activation, neutral protease induction, proteoglycan degradation and synthesis) have been determined. Among the 20 IL-1 beta mutant polypeptides we present here, four showed a markedly reduced activity in cartilage matrix assays without any significant change in their binding to the cartilage matrix cells (chondrocytes). Furthermore, some of these mutants were specific partial agonists of the effects of IL-1 on connective tissue since they have a low affinity for thymocytes. PMID- 8436118 TI - Structure/function relationships in the pyruvate dehydrogenase complex from Azotobacter vinelandii. Role of the linker region between the binding and catalytic domain of the dihydrolipoyl transacetylase component. AB - The role of the hinge region between the binding domain and the catalytic domain in dihydrolipoyl transacetylase (E2p) from Azotobacter vinelandii was addressed by deletion mutagenesis. Mutated dihydrolipoyl transacetylase proteins were constructed with a deletion of 11 amino acids in the hinge region between the binding domain and the N-terminal part of the catalytic domain of E2p [E2p(pAPE1)] and with a further deletion of 9 amino acids into the N-terminal sequence protruding from the globular structure of the catalytic domain [E2p(pAPE2)] and found to take part in the intratrimer interaction. Both proteins behaved as wild-type E2p with respect to catalytic activity and quaternary structure. The interaction of the peripheral components pyruvate dehydrogenase (E1p) and lipoamide dehydrogenase (E3) with the mutated E2p proteins was studied. E2p(pAPE1) assembles to a trimeric pyruvate dehydrogenase complex (PDC) with 15% decreased complex activity. No difference in affinity towards the peripheral components was detected. Upon binding of E3, E2p(pAPE2) dissociates into trimers and monomers. At saturation, two dimers of E3 were bound/E2p monomer instead of one dimer/E2p chain in trimeric wild-type E2p or E2p (pAPE1). The monomeric E2p species was catalytically inactive. Upon binding of excess E1p, some monomer formation of the E2p mutant took place. E1p however can prevent monomerization by E3. It is concluded that E1p is bound between two different E2p chains in the trimer. The substrates CoA and acetyl-CoA also prevent monomerization because they are bound by amino acid residues of two different E2p chains. In the presence of CoA no difference in affinity with respect to E1p and E3 binding was observed. CoA (and acetylCoA) also prevent dissociation of the 24-subunit core structure of wild-type E2p when added before addition of E1p or E3. Therefore, it seems likely that in vivo A. vinelandii PDC is based on a 24-subunit E2p core, like Escherichia coli PDC. A functional difference between complexes based on a trimer or a 24-subunit core has not been observed. A role of the hinge region as a spacer to allow binding of E1p or E3 seems unlikely. The results are discussed on the basis of the three-dimensional structure of the catalytic domain. PMID- 8436119 TI - Isolation and molecular characterization of a hyperglycemic neuropeptide from the sinus gland of the terrestrial isopod Armadillidium vulgare (Crustacea). AB - The major peptide from the sinus gland of the terrestrial isopod Armadillidium vulgare (Crustacea) has been extracted and purified by reverse-phase HPLC. This neuropeptide exhibited a high hyperglycemic activity and was therefore named A. vulgare crustacean hyperglycemic hormone (Arv-CHH). Its average molecular mass measured by mass spectrometry was 8729.3 Da. Its complete amino acid sequence was determined by a combination of Edman degradation and mass spectrometry. The N terminal amino acid was found to be unblocked, the C-terminal residue was found amidated and none of the other 72 residues was affected by any post-translational modification. Disulfide bond assignment was made unambiguously by mass spectrometry and Edman degradation was performed on peptides produced by enzymatic cleavage. Relationships with other, similar neuropeptides from decapod sinus glands are discussed. PMID- 8436120 TI - Facile sulfitolysis of the disulfide bonds in oxidized thioredoxin and glutaredoxin. AB - Thioredoxins and glutaredoxins, in their oxidized form, possess a single disulfide bridge located on an edge of the small compact molecules. In contrast to most other disulfide-containing proteins, this S-S bridge is cleaved by millimolar concentrations of sulfite in the absence of protein denaturing agents at pH 7-8 and ambient temperature; however, the reaction is not quantitative. Sulfitolysis of Escherichia coli thioredoxin was found to be associated with an increase in fluorescence at 345 nm. A comparative study of sulfitolysis in 12 different thioredoxins and glutaredoxins of bacterial and plant origin has been made. Although they are all thought to be highly conserved in three-dimensional structure, their reactivities towards sulfite and the effects of 6 M guanidinium chloride (not affecting, or enhancing sulfitolysis) vary strongly in the series, with E. coli thioredoxin being less reactive and plant thioredoxins and E. coli glutaredoxin being more susceptible molecules. Contrary to expectation, reaction with sulfite is not generally correlated with the presence of negatively or positively charged amino acid residues near the disulfide loop but is determined by individual sequence and surface features in every single protein. These results confirm our hypothesis that thioredoxin sulfitolysis and inactivation [Wurfel, M., Haberlein, I., Follmann, H. (1990) FEBS Lett. 268, 146-148] can occur in plant cells under physiological conditions and provide a biochemical rationale for the phytotoxicity of SO2. PMID- 8436121 TI - Purification, characterization, crystallisation and X-ray analysis of selenomethionine-labelled hydroxymethylbilane synthase from Escherichia coli. AB - Hydroxymethylbilane synthase (HMBS) catalyses the conversion of porphobilinogen into hydroxymethylbilane, a linear tetrapyrrolic intermediate in the biosynthesis of haems, chlorophylls, vitamin B12 and related macrocycles. In the course of an investigation of the crystal structure of this enzyme, we intended to follow a new strategy to obtain the X-ray phase information, i.e. the collection of multiwavelength anomalous diffraction data from a crystal of a seleno-L methionine (SeMet)-labelled variant of the protein. We have expressed and purified HMBS from Escherichia coli (34268 Da) in which all (six) methionine (Met) residues are replaced by SeMet. Complete replacement, as shown by amino acid composition analysis and by electrospray mass spectrometry, was achieved by growing the Met-requiring mutant E. coli PO1562 carrying the plasmid pPA410 in a medium containing 50 mg/l SeMet as the sole source of Met. [SeMet]HMBS exhibits full enzyme activity, as reflected by unchanged steady-state kinetic parameters relative to native enzyme. Rhombohedral crystals of [SeMet]HMBS could be grown at the pH optimum (7.4) of the enzyme (solutions containing 30 mg/ml protein, 0.4 mM EDTA, 20 mM dithiothreitol, 3 M NaCl and 15 mM Bristris-propane buffer were equilibrated by vapour diffusion at 20 degrees C against reservoirs of saturated NaCl). However, being very thin plates, these crystals were not suitable for X ray analysis. Alternatively, rectangular crystals were obtained at pH 5.3 using conditions based on those reported for wild-type HMBS [sitting drops of 50 microliters containing 6-7 mg/ml protein, 0.3 mM EDTA, 15 mM dithiothreitol, 10% (mass/vol.) poly(ethylene glycol) 6000 and 0.01% NaN3 in 0.1 M sodium acetate were equilibrated by vapour diffusion at 20 degrees C against a reservoir of 10 20 mg solid dithiothreitol]. X-ray diffraction data of the crystals were complete to 93.8% at 0.21 nm resolution and showed that [SeMet]HMBS and native HMBS crystallise isomorphously. A difference Fourier map using FSeMet-Fnative and phases derived from the native structure, which has recently been determined independently by multiple isomorphous replacement, showed positive difference peaks centered at or close to where the sulphur atoms of the Met side chains appear in the native structure. In addition, paired positive/negative peaks in the difference map near the cofactor of HMBS indicate conformational differences in the active site, probably due to differences in the state of oxidation of the cofactor in the two crystalline samples. PMID- 8436122 TI - Interaction of the colicin-A pore-forming domain with negatively charged phospholipids. AB - The interaction of colicin-A thermolytic fragment with negatively charged liposomes was studied by fluorescence spectroscopy. 1,2-Dioleoyl-sn-glycero-3 phospho-1-sn-glycerol (Ole2GroPGro) containing liposomes do not significantly alter the fluorescence properties of the protein, and thus cannot give much information about this interaction. 1,2-Bis(9,10-dibromooleoyl-sn-glycero-3 phospho-1-sn-glycerol (Br4Ole2GroPGro) is easily synthesized by addition of bromine atoms to the double bond located at the mid-point of the fatty-acid acyl chain of Ole2GroPGro. The brominated phospholipid forms vesicles that strongly quench the protein fluorescence emission. The results presented here show that conversion of Ole2GroPGro to Br4Ole2GroPGro does not change either the affinity for the protein or the extent of lipid binding. This observation allows for the estimation of the distribution of the quenching phospholipid molecules around the fluorophores [Yeager, M. D. & Feigenson G. W. (1990) Biochemistry 29, 4380-4392]. Binding of the protein to the vesicles is an irreversible process, since inserted molecules do not dissociate from the vesicle. From steady-state measurements, it can be concluded that in the membrane-bound form, the tryptophans are located within quenching distance of the bromine atoms, i.e. close to the lipid head group/hydrocarbon boundary, completely accessible to the quencher, protected from the polar phase and that the maximum number of phospholipid molecules in contact with the fluorescent domain of the protein is nine. PMID- 8436123 TI - Reduction and mobilization of iron by a NAD(P)H:flavin oxidoreductase from Escherichia coli. AB - Iron is an essential element in all living cells. Solubilization, uptake and transport of iron by microorganisms is controlled by highly efficient and specific Fe(3+)-chelating agents named siderophores. However, mechanisms of mobilization of iron from ferrisiderophores are still enigmatic. Here, we demonstrate that Escherichia coli contains a powerful enzymatic system for the reduction of ferrisiderophores. Siderophores have a much lower affinity for ferrous iron, which then can be liberated. This system has been previously purified and characterized as a NAD(P)H:flavin oxidoreductase [Fontecave, M., Eliasson, R. and Reichard, P. (1987) J. Biol. Chem. 262, 12,325-12,331)]. It catalyzes the reduction of free flavins, FMN, FAD or riboflavin by NADH or NADPH. Reduced flavins, in turn, transfer their electrons to physiological ferric complexes: ferrisiderophores, ferric citrate and ferritins. The reaction is inhibited by molecular oxygen and greatly stimulated by Fe(2+)-acceptors such as ferrozine or the iron-free form of ribonucleotide reductase subunit R2. We suggest that the reduction and the mobilization of iron from ferrisiderophores in the cell might be regulated by the presence of physiological ferrous traps such as apoproteins. PMID- 8436124 TI - Comparison of stability properties of lactate dehydrogenase B4/epsilon-crystallin from different species. AB - epsilon-Crystallin occurs as an abundant lens protein in many birds and in crocodiles and has been identified as heart-type lactate dehydrogenase (LDH-B4). Lens proteins have, due to their longevity and environmental conditions, extraordinary requirements for structural stability. To study lens-protein stability, we compared various parameters of LDH-B4/epsilon-crystallin from lens and/or heart of duck, which has abundant amounts of this enzyme in its lenses, and of chicken and pig, which have no epsilon-crystallin. Measuring the thermostability of LDH-B4 from the different sources, the t50 values (temperature at which 50% of the enzyme activity remains after a 20-min period) for LDH-B4 from duck heart, duck lens and chicken heart were all found to be around 76 degrees C, whereas pig heart LDH-B4 was less thermostable, having a t50 value of 62.5 degrees C. A similar tendency was found with urea inactivation studies. Plotting the first-order rate constants obtained from inactivation kinetic plots against urea concentration, it was clear that LDH-B4 from pig heart was less stable in urea than the homologous enzymes from duck heart, chicken heart and duck lens. The duck and chicken enzymes were also much more resistant against proteolysis than the porcine enzyme. Therefore, it is concluded that avian LDH-B4 is structurally more stable than the homologous enzyme in mammals. This greater stability might make it suitable to function as a crystallin, as in duck, but is not necessarily associated with high lens expression, as in chicken. PMID- 8436125 TI - Products of enzymatic reduction of benzoyl-CoA, a key reaction in anaerobic aromatic metabolism. AB - Benzoyl-coenzyme A is the most common central intermediate of anaerobic aromatic metabolism. Studies with whole cells of different bacteria and in vitro had shown that benzoyl-CoA is reduced to alicyclic compounds, possibly via cyclohexadiene intermediates. This reaction is considered a 'biological Birch reduction'. We have elucidated by NMR techniques the structures of six products of [ring 13C6]benzoate reduction. The reaction is catalyzed by extracts from cells of a denitrifying Pseudomonas strain K172 anaerobically grown with benzoate and nitrate as sole carbon and energy sources. The assay mixture contained [ring 13C6]benzoate plus traces of [U-14C]benzoate, Mg2+, ATP, coenzyme A (CoA), and Ti(III) as reductant. The use of the multiply 13C-labelled precursor increases the sensitivity of NMR detection and allows the analysis of crude product mixtures by two-dimensional coherence transfer procedures such as total correlation 13C-NMR spectroscopy and 13C-filtered 1H-NMR spectroscopy. The time course of product formation is consistent with the following order of events. Benzoyl-CoA is formed from benzoate via benzoate-CoA ligase. The first ring reduction product observed is cyclohex-1,5-diene-1-carboxyl-CoA. The next intermediate is 6-hydroxycyclohex-1-ene-1-carboxyl-CoA which is derived from the diene by addition of water. Part of the diene seems to be reduced to cyclohex-1 ene-1-carboxyl-CoA which becomes hydrated to trans-2-hydroxycyclohexane-1 carboxyl-CoA; these two intermediates may be side products in vitro. The first non-cyclic intermediate formed by beta-oxidation is 3-hydroxypimelyl-CoA. This aliphatic C7 dicarboxylic acid is proposed to be oxidized via glutaryl-CoA and crotonyl-CoA to three molecules of acetyl-CoA and one molecule of CO2. A similar product pattern was observed in the benzoate-degrading phototrophic bacterium Rhodopseudomonas palustris. This indicates that the enzymatic reduction of benzoyl-CoA may be mechanistically similar in different anaerobes. PMID- 8436126 TI - Inhibition of proton-translocating transhydrogenase from photosynthetic bacteria by N,N'-dicyclohexylcarbodiimide. AB - The effects of N,N'-dicyclohexylcarbodiimide [(cHxN)2C] on the proton translocating enzyme, NAD(P) H(+)-transhydrogenase (H(+)-Thase), from two species of phototrophic bacteria have been investigated. The polypeptides of H(+)-Thase from Rhodobacter capsulatus are membrane-associated, requiring detergent to maintain solubility. The enzyme from Rhodospirillum rubrum, however, has a water soluble polypeptide (Ths) and a membrane-associated component (Thm) which, separately, have no activity but which can be fully reconstituted to give a functional complex. Two observations suggest that (cHxN)2C inhibited H(+)-Thase from both species by modification either close to or at the NADP(H)-binding site on the enzyme: (a) the presence of NADP+ or NADPH caused increased inhibition by (cHxN)2C and (b) after treatment of the purified enzyme from Rb. capsulatus with (cHxN)2C, the release of NADP+ became rate-limiting, as evidenced by a stimulated rate of NADPH-dependent reduction of acetylpyridine adenine dinucleotide by NADH. Experiments in which Ths and Thm from R. rubrum were separately treated with (cHxN)2C then reconstituted with the complementary, untreated component revealed that the NADP(H)-enhanced modification by (cHxN)2C was confined to Thm. In contrast to some experiments with mitochondrial H(+)-Thase [Wakabayashi, S. & Hatefi, Y. (1987) Biochem. Int. 15, 667-675], there was no protective effect of either NAD+ or NADH on the inhibition by (cHxN)2C of enzyme from photosynthetic bacteria. However, amino acid sequence analysis of proteolytic fragments of Ths revealed that the NAD(H)-protectable, (cHxN)2C-reactive glutamate residue in mitochondrial H(+)-Thase might be replaced by glutamine in R. rubrum. PMID- 8436127 TI - Unidirectional arginine transport in reconstituted plasma-membrane vesicles from yeast overexpressing CAN1. AB - Amino acids are accumulated in Saccharomyces cerevisiae by strictly unidirectional influx systems. To see whether cellular compartmentation causes this unusual amino-acid-transport behaviour, arginine transport was studied in plasma-membrane vesicles. The arginine permease gene CAN1 was overexpressed in S. cerevisiae RH218a and in a permease-deficient mutant RS453 (can1). Reconstituted plasma-membrane vesicles from these transformants, energized by incorporated cytochrome-c oxidase, showed 3-4-fold increased rates of arginine uptake compared to vesicles from wild-type cells. The KT values were 32.5 microM in vesicles from wild-type and 28.6 microM in vesicles from transformed cells; the corresponding in vivo values were 17.5 microM and 11.4 microM, respectively. It could be demonstrated that unidirectional arginine transport and accumulation also exist in vesicles; thus, unidirectional influx is not related to cellular compartmentation. PMID- 8436128 TI - Overexpression of trypanosomal triosephosphate isomerase in Escherichia coli and characterisation of a dimer-interface mutant. AB - In this paper, the successful expression of trypanosomal triosephosphate isomerase (TIM) from Trypanosoma brucei brucei to high yield in Escherichia coli, using a T7-polymerase-based expression system, is described. Overexpressed trypanosomal TIM is fully active. The measured physicochemical properties of this recombinant TIM and TIM purified from trypanosomes are indistinguishable. Crystals of recombinant TIM have been grown in the presence of 2.4 M ammonium sulphate under the same conditions as for trypanosomally expressed TIM. The recombinant TIM crystal structure has been refined at 0.23 nm resolution; no differences were detected between this structure and the original crystal structure. A TIM mutant was made in which a unique dimer-interface histidine residue (His47) was changed into an asparagine. This variant ([H47N]TIM) could be expressed and purified to homogeneity by a procedure which was somewhat different from the purification of recombinant wild-type TIM. It is shown that the [H47N]TIM dimer is considerably less stable than wild-type trypanosomal TIM. The catalytic activity of [H47N]TIM is concentration dependent. The dilution dependent inactivation is reversible. His47 is involved in a water-mediated hydrogen bond with Asp385 of the other subunit. The lower stability of the [H47N]TIM dimer implies that this water-mediated hydrogen bond is important for the stability of the TIM dimer. PMID- 8436129 TI - Biochemical, immunological and ultrastructural characterization of aggregation substances encoded by Enterococcus faecalis sex-pheromone plasmids. AB - The sex-pheromone system of Enterococcus faecalis can be viewed as a unique and highly efficient plasmid-collection mechanism. The contact needed for transfer of the conjugative sex-pheromone plasmids is mediated by an adhesin, called aggregation substance, which is encoded by these plasmids. We show here that for 17 of the 18 sex-pheromone plasmids (pAM373 being the exception) described to date, their adhesins are immunologically related to each other. In each case, we observed the presence of an N-terminal fragment of about 78 kDa in addition to the 137-kDa form of mature aggregation substance. The cross-reactions were different for the various plasmids. In the case of pPD1 the 78-kDa fragment reacted only weakly. The aggregation substance encoded by sex-pheromone plasmid pAD1 (Asa1) was characterized in detail. The conditions used for SDS/PAGE had a drastic influence on the migration behavior of mature aggregation substance and differently migrating, interconvertible forms were identified. Preliminary data indicate that Asa1 might be a glycoprotein. Antibodies were isolated which are directed against the N- and C-terminal parts of aggregation substance. They showed about the same reactivity on Western blots; however, only antibodies directed against the N-terminal part of the aggregation substance could inhibit the bacterial cell/cell contact. The reactions of the two antibody preparations with induced cells of E. faecalis was analyzed by transmission electron microscopy. The results indicated that especially the N-terminal part of aggregation substance is exposed on the cell surface of E. faecalis; the C terminal part seems to be much less exposed. PMID- 8436130 TI - Characterization of cardiac fatty-acid-binding protein from human placenta. Comparison with placenta hepatic types. AB - When a 105,000 x g supernatant of human placenta was incubated with [1-14C]oleate and subjected to Sephadex G-75 gel filtration and HPLC, two fatty-acid-binding protein (FABP) peaks were obtained. One of these, when further purified by carboxymethyl-cellulose, gave one 15.3-kDa FABP with pI5.3. The other, when chromatographed on DEAE cellulose, separated into two 14.2-kDa FABP with pI6.9 and 5.4. Purity of the proteins was checked by SDS/PAGE. Molecular mass, pI, immunochemical properties and amino acid compositions all indicated that 15.3-kDa FABP was of the cardiac type, whereas both 14.2-kDa FABP were of the hepatic type. Cardiac FABP did not cross-react with hepatic proteins. When tested for the acceptor/donor properties of these FABP, hepatic types were found to be better candidates than cardiac in uptaking fatty acids from liposomes. Cardiac FABP, on the other hand, acted in a more efficient way as a donor, indicating a distinct role of these proteins in human placenta, which furnishes a multiorgan system for the developing fetus. PMID- 8436131 TI - Localization of the tightly bound divalent-cation-dependent and nucleotide dependent conformation changes in G-actin using limited proteolytic digestion. AB - Using proteolytic susceptibility as a probe, we have identified four regions of the actin polypeptide chain where structural rearrangements, dependent on the nature of the tightly bound metal ion and/or nucleotide, take place. Replacement of the tightly bound Ca2+ by Mg2+ in ATP-actin strongly affected the regions around Arg26 and Lys68, as judged from nearly complete inhibition of tryptic cleavages of the polypeptide chain at these residues. It also significantly diminished the rates of splitting by trypsin of the peptide bonds involving carbonyl groups of Arg372 and of Lys373 in the C-terminal segment. Conversion of ATP-actin to ADP-actin (with Mg2+ as the tightly bound cation) abolished the protective effect of Mg2+ on specific tryptic cleavage and, in contrast, largely inhibited proteolysis at specific sites for subtilisin and for a novel protease from Escherichia coli A2 strain within a surface loop of residues 39-51. We also examined the effect of proteolytic cleavage or chemical modification at certain sites on the kinetics of proteolysis at other sites of the molecule. These experiments demonstrated structural relationships between loop 39-51 and regions involving Lys61 and Lys68. It is suggested that the conformational transitions reflected in the observed changes in proteolytic susceptibility may underlie the known influence of the nature of the tightly bound cation and nucleotide on the kinetics of actin polymerization and stability of the polymer. PMID- 8436132 TI - Involvement of the Arg179 in the active site of human IL-6. AB - Three internal-amino acid deletions of amino acids 171-179 of human interleukin 6 (IL-6) were introduced at the cDNA level. While all deletion proteins were biologically inactive, immunoprecipitations with a set of conformation-specific anti-(IL-6) monoclonal antibodies showed that only mutant delta 177-179 does not present major alterations in folding. This finding, together with the observation that delta 177-179 is not able to compete with IL-6 for binding to the soluble human IL-6 receptor, suggested that some or all of these three residues participate to the composition of the receptor-binding site of human IL-6. A large number of single-amino-acid-substitution mutants were generated in residues 177, 178 and 179. Their detailed analysis revealed that Arg179 is crucial for activity in mouse cells, because all amino acid substitutions in this position cause a dramatic drop of biological activity on murine hybridoma cells without affecting the overall protein folding. The only substitution which preserved some residual activity was the conservative Arg to Lys change. This demonstrates the absolute requirement for a positive charge in position 179 for the interaction of human IL-6 with its receptor. PMID- 8436133 TI - Kinetics and mechanism of an NADPH-dependent succinic semialdehyde reductase from bovine brain. AB - An NADPH-dependent succinic semialdehyde reductase has been purified from bovine brain by several chromatographic procedures. The preparation appeared homogeneous on SDS/PAGE. The enzyme is a monomeric protein with a molecular mass of 28 kDa. A number of properties of the bovine brain enzyme, such as substrate specificity, specific activity, molecular mass, optimum pH, amino acid composition, and kinetic parameters, have been determined and compared with those reported for preparations from other sources. The results indicate that the enzyme isolated from bovine brain in the present study is different from those reported for preparations from other sources. The inhibition kinetic patterns obtained when the products of the reaction or substrate analogs are used as inhibitor of the reaction catalyzed by the enzyme are consistent with an ordered sequential mechanism involving the formation of an intermediate ternary complex and in which NADPH is the first substrate to bind the enzyme. PMID- 8436134 TI - Differentially expressed patterns of glycosaminoglycan structure in heparan sulfate proteoglycans and free chains. AB - The metabolic relationships between heparan sulfate proteoglycans, free chains, and oligosaccharides in different cell locations were evaluated by comparing their glycosaminoglycan structure. Metabolically labeled heparan sulfate proteoglycans of BALB/c 3T3 cell layers and in conditioned medium were compared with the heparan sulfate free chains (modal mass = 10 kDa) and oligosaccharides (modal mass = 3 kDa) of the cells. Nonlytic, in situ digestion with heparitinase I indicated that 90% of proteoglycans, 70% of the free chains, and 20% of the oligosaccharides were enzyme accessible, but there was no evidence using competitive ligands for binding of the products to the cell surface via the glycosaminoglycan moieties. Structurally, the membrane proteoglycans were the most O-/N-sulfated and yielded more tri- and tetra-sulfated di- and tetra saccharides by nitrous acid degradation. In contrast, the side chains of medium proteoglycans were less sulfated and more polydisperse in mass, suggesting that most medium proteoglycans are not processed from membrane precursors. The heparan sulfate free chains were of lower mass, less sulfated, and more heterogeneous in distribution of the anionic groups than were proteoglycan side chains. Corroborating analytical heparitinase I digestion indicated that generation of di and tetra-saccharides proportionately increased from membrane proteoglycan, to cell free chain, to medium proteoglycan categories. Because the structural patterns of the heparan sulfate free chains did not reveal a clear relationship with the side chains of the major proteoglycans, their origin was further probed by [3H]BH4-labeling of the reducing terminus under varying stringencies. The end labeled residues obtained by nitrous or strong acid hydrolysis of the free chains showed insignificant amounts of galactose and xylose, but rather glucosamine N sulfate and a residue likely generated from glucuronate. The effective labeling that was achieved with weak alkali indicated that covalent oligopeptide is not present. In summary, the heparan sulfate free chains, which in part are components of the cell surface, are of relatively low mass, are unassociated with covalent peptide, and most probably have a disaccharide motif of glucosamine N sulfate and a uronate residue at the reducing end. Taken together, these observations suggest that the free chains originate by processing of precursor heparan sulfate proteoglycans on the cell surface via an endoglycosidase acting on an N-sulfated portion of the original polymer. PMID- 8436135 TI - Kinetics of biliary secretion of chylomicron remnant cholesterol (esters) in the rat. AB - Chylomicrons labelled with [3H]cholesterol/[3H]cholesterol esters in a ratio of 25.5: 74.5, were rapidly removed from rat serum in vivo, and taken up predominantly by the parenchymal liver cells (88.2%) of the hepatic uptake at 15 min after injection). Lactoferrin reduced the liver uptake of chylomicron remnants by 72%, at 20 min after injection. It appeared that the free cholesterol which is present in the chylomicrons is not readily exchanged within the used time period with other cholesterol pools in the animal. Between 10-60 min after injection of 3H-labelled chylomicrons, cholesterol esters are hydrolysed in the liver. Appearance of radioactivity in bile was rapid and at 3, 24 and 72 h after injection, 13.4%, 44.0% and 70.0%, respectively, of the injected dose appeared in bile, mainly as bile acids (> 90%). Lactoferrin reduced the biliary secretion of radioactivity, especially during the first hour after injection. The total amount of radioactivity recovered was 58.0% of the injected dose at 72 h after injection. After injection of beta-migrating very low-density lipoprotein labelled with [3H]cholesterol/[3H]cholesterol esters in a ratio of 23.5:76.5, the maximum amount of radioactivity secreted in bile was much lower than with chylomicrons (2.6% cf. 5.2% at 1 h after injection), although the kinetics of the initial liver association and cholesterol ester hydrolysis were even more rapid. Biliary accumulation of radioactivity was also lower with 50.5% of the injected dose recovered at 72 h after injection. It can be concluded from these studies that the processing of chylomicron remnant cholesterol components in the liver and the subsequent secretion in the bile mainly as bile acids is very efficient. The efficient liver uptake of chylomicron remnants by the liver remnant receptor is thereby essential to achieve this high percentage of removal, thus protecting against extrahepatic cholesterol (ester) deposition. PMID- 8436136 TI - Neurotrophin-3 receptors in the developing chicken retina. AB - Neurotrophin 3 (NT-3) had specific high-affinity receptors (HNT-3R) in the developing chick retina at all ages between embryonic day (E) 4 and E14. The affinity of HNT-3R for 125I-NT-3 did not change with the developmental state. A dissociation constant (kd) of 13 pM was obtained. However, the amount of HNT-3R appeared to be developmentally regulated; the number of receptors/cell increased from E4 up to E6-7 (coinciding with the main onset of neuronal differentiation), then decreased until E9 and increased again by E12, when all retinal cells were differentiated. Kinetic and cross-linking experiments showed that HNT-3R from two prototypical developmental ages, E7 and E14, were different. E7 and E14 HNT-3R could be distinguished from each other on the basis of different inhibition patterns of 125I-NT-3 binding in the presence of nerve growth factor or brain derived neurotrophic factor. Chemical cross-linking of increasing concentrations of 125I-NT-3 to its receptors showed (a) one 100-kDa band corresponding to neurotrophin low-affinity receptors in both E7 and E14 cells; (b) one 130-kDa band also present in both E7 and E14 cells. Densitometric measurements showed that this 130-kDa band behaved as HNT-3R in E14 cells (kd approximately 10 pM) but not in E7 cells (kd > or = 0.2 nM). Furthermore, the 130-kDa band in both E7 and E14 retinal cells displayed a trk-like immunoreactivity. Our data show that, in neurons, one particular neurotrophin may induce different actions mediated through distinct and specific receptors. PMID- 8436137 TI - Site-directed mutagenesis and chemical modification of histidine residues on an alpha-class chick liver glutathione S-transferase CL 3-3. Histidines are not needed for the activity of the enzyme and diethylpyrocarbonate modifies both histidine and lysine residues. AB - Each chick liver glutathione S-transferase CL 3 subunit contains three histidine residues: His142, His158 and His228. CL 3-3 can be inactivated by treating with diethylpyrocarbonate. The inactivation process is pH dependent and the pKa of the modified residue is 6.4. The second-order inhibition rate constant is 741 M-1min 1 at pH 7.0. Based on difference-spectrum and kinetic analysis, inactivation coincides with the modification of one histidine residue. However, hydroxylamine treatment of the diethylpyrocarbonate-modified enzyme only partially restored the activity (30-50%) of CL 3-3. By tryptic mapping and amino acid sequence analysis, His228 and Lys14 have been identified as the modified residues. Mutants with histidine to serine replacement (H142S and H158S) or C-terminal histidine deletion (des-H228) were constructed and over-expressed in Spodoptera frugiperda cells using a baculovirus system. The mutants are enzymically active. Furthermore, the des-H228 mutant can be inactivated by diethylpyrocarbonate. These results support the conclusion that histidines are not involved in the enzymic mechanism of CL 3-3. PMID- 8436138 TI - Importance of the conserved active-site residues Tyr7, Glu106 and Thr199 for the catalytic function of human carbonic anhydrase II. AB - The catalytic mechanism of carbonic anhydrase includes the reaction of a zinc bound hydroxide ion with the CO2 substrate. This hydroxide ion is part of a hydrogen-bonded network involving the conserved amino acid residues Thr199, Glu106 and Tyr7. To investigate the functional importance of these residues, a number of site-specific mutants have been made. Thus, Thr199 has been changed to Ala, Glu106 to Ala, Gln and Asp, and Tyr7 to Phe. The effects of these mutations on catalyzed CO2 hydration and ester hydrolysis have been measured, as well as the binding of some inhibitors. The results show that the CO2 hydration activity of the mutant with Phe7 is only marginally reduced, whereas the esterase activity is larger than that of unmodified enzyme. It is concluded that Tyr7 is not a functionally required element of the hydrogen-bonded network. The CO2 hydration activity (kcat as well as kcat/Km) and the esterase activity of the mutant with Ala199 are reduced about 100-fold. The affinity for the sulfonamide inhibitor, dansylamide, is only slightly reduced while the mutant has an enhanced affinity for bicarbonate and the anionic inhibitor, SCN-. The activities of the mutants with Ala106 and Gln106 are also reduced. The reduction of the esterase activity is about 100-fold, while kcat for CO2 hydration has decreased by a factor of 1000. The parameter kcat/Km is only about one order of magnitude smaller for these mutants than for the unmodified enzyme. The binding of dansylamide and another sulfonamide inhibitor, acetazolamide, are about 20-times weaker to the mutant with Gln106 than to unmodified enzyme. These results suggest important roles for Thr199 and Glu106 in carbonic anhydrase catalysis. The mutant with Asp106 is almost fully active suggesting that the structure has undergone a compensatory change to maintain the interaction between residue 106 and Thr199. PMID- 8436139 TI - Cholesterol metabolism in rat adrenal gland during reversible endotoxic shock. AB - The adrenal glands have a crucial role for survival during endotoxic shock. Cholesterol is the obligatory intermediary in corticosteroid biosynthesis; thus any alteration in either the availability of cholesterol or in the ability of the adrenal gland to use cholesterol would have a profound effect on corticosteroid production. We have studied the effect of Escherichia coli endotoxin on cholesterol metabolism, injecting lipopolysaccharide (1.6 mg/100 g body) from E. coli 0111:B4 into the tail vein of male Wistar rat. Previous studies from this laboratory have shown that this dose of lipopolysaccharide induces a reversible endotoxic shock. During reversible endotoxic shock there is an alteration in plasma cholesterol; plasma total-cholesterol levels increase mainly at 6-24 h post-lipopolysaccharide injection, whereas cholesterol in high-density lipoproteins shows no significant variations, except a slight but significant decrease at 24 h. The cholesterol content in adrenal gland is diminished in endotoxemic rat, this decrease is more important at 6-24 h after endotoxin injection. We have also measured the acyl-CoA:cholesterol O-acyltransferase (ACAT) and cholesterol-esterase (CEH) activity during endotoxic shock. ACAT activity decreases after lipopolysaccharide injection. ACAT activity in endotoxemic rats is approximately 35-40% of the activity in control rats. This decrease is due to a defect in the functional capacity of the enzyme, since with exogenous cholesterol there is no significant variation in the ACAT activity. CEH activity, in contrast, increases during endotoxic shock; it shows a maximum (twofold the activity seen in control rats) at 6 h after lipopolysaccharide injection. These results show that lipopolysaccharide injection modifies cholesterol metabolism in plasma and in the adrenal gland, either directly or by mediators. PMID- 8436140 TI - The primary structure of turtle Cu,Zn superoxide dismutase. Structural and functional irrelevance of an insert conferring proteolytic susceptibility. AB - A copper,zinc superoxide dismutase, has been isolated from the marine turtle Caretta caretta and the complete amino acid sequence obtained. The sequence was determined by isolation and analysis of peptides obtained after cleavage of the carboxymethylated apoenzyme with trypsin or Staphylococcus aureus protease. Turtle superoxide dismutase consists of 166 amino acid residues, which represents the largest number to date for a cytosolic copper,zinc superoxide dismutase. The comparison of this amino acid sequence with that of bovine superoxide dismutase revealed a one-residue C-terminal extension, two single residue insertions and a 12-residue insertion in the N-terminal region, in turtle superoxide dismutase. The new segment consists of a threefold repeating sequence and was found to be the site for selective proteolytic attack by trypsin under native conditions. The biochemical characteristics, the spectroscopic and catalytic properties as well as the thermal stability and the resistance to irreversible denaturation, were carefully examined and were very similar to those of other superoxide dismutases. These results indicate that the presence of the new polypeptide segment does not affect the main folding of the chain and the quaternary structure, nor the functional parameters of turtle superoxide dismutase. The possibility that the new insert constitutes a loop excluded from the protein scaffold providing the framework of the active site is also discussed. PMID- 8436141 TI - Molecular cloning and nucleotide sequence of the gene for pyruvate kinase of Bacillus stearothermophilus and the production of the enzyme in Escherichia coli. Evidence that the genes for phosphofructokinase and pyruvate kinase constitute an operon. AB - Pyruvate kinase from Bacillus stearothermophilus is an allosteric enzyme activated by AMP or ribose 5-phosphate but not by fructose 1,6-bisphosphate. The gene for the enzyme was cloned in Escherichia coli and its entire nucleotide sequence was determined. The deduced amino acid sequence consisted of 587 residues and the molecular mass was calculated to be 62 317 Da. The sequence was highly similar to other pyruvate kinases, indicating that they have the same evolutional origin. Similarly to the E. coli enzymes, the enzyme does not contain an N-terminal domain, in contrast to the eukaryotic pyruvate kinases. However, the Bacillus stearothermophilus enzyme had an extra C-terminal sequence consisting of about 110 amino acid residues. A phosphoenolpyruvate-binding motif, which is observed in pyruvate phosphate dikinase, phosphoenolpyruvate: sugar phosphotransferase system enzyme I and phosphoenolpyruvate synthase, was present in the extra C-terminal sequence. There was an open reading frame upstream of the pyruvate kinase gene. The homology of the sequence showed that the gene encodes phosphofructokinase. Both phosphofructokinase and pyruvate kinase were expressed in E. coli cells, and the evidence suggesting that both genes constitute an operon is presented. PMID- 8436142 TI - Affinity labelling of sorbitol dehydrogenase from sheep liver with alpha-bromo beta-(5-imidazolyl)propionic acid. AB - The metal-directed alkylating agent DL-alpha-bromo-beta-(5- imidazolyl)propionic acid (BrImPpOH) is shown to be an affinity-labelling reagent for sheep liver sorbitol dehydrogenase (SDH). As previously found for horse liver alcohol dehydrogenase (ADH), it modifies a cysteine ligand to the active-site zinc. In this case it is selectively incorporated (over 90%) at Cys43 in each of the four polypeptide chains/protomers of sheep liver SDH. Incorporated reagent and residual activity correlated. The first order inactivation constant, K2, and KEI, the dissociation constant for SDH and BrImPpOH, have been determined at different pH. The reactivity of BrImPpOH for SDH is higher than that for horse liver and yeast ADH. The protection of SDH against BrImPpOH inactivation by buffers and other molecules shows some similarities to that with horse liver ADH. However, sheep liver SDH bound BrImPpOH, imidazole and phosphate ions much weaker than liver ADH. The pKa values from the plot of log (k2/KEI) against pH are approximately 7.0 and 8.8-8.9. The former pKa value probably represents ionization of an imidazole group and the latter the zinc/water ionization in SDH. These pKa values are similar to those found for horse liver ADH. They are apparently not noticeably influenced by a second cysteine ligand in liver ADH being replaced by a proposed glutamic acid residue as a ligand to the catalytic zinc in SDH. The plot of logk2 against pH shows pKa values around 7.0 and 9.2 for the SDH-BrImPpOH-complex. The pKa of 7.0 is the same as for log(k2/KEI), and indicates no significant perturbation due to the binding of BrImPpOH to SDH. The pKa around 9.2 indicates perturbation of the zinc/water ionization or the ionization of Cys43. PMID- 8436143 TI - Effect of mutation of an amino acid residue near the catalytic site on the activity of Bacillus stearothermophilus alpha-amylase. AB - Site-directed mutagenesis of a thermostable alpha-amylase from Bacillus stearothermophilus was performed to assess the role of amino acid residues near the catalytic site in catalysis. Asn329 is presumed to be adjacent to the proposed catalytic residue Asp331. Its mutation to Lys, which is found at the corresponding position in pullulanase, resulted in the loss of 99.7% of the activity, while the mutation to Asp or Val did not drastically reduce the activity. The mutation to Val altered the temperature/activity profile so that the activity was reduced to 25% of wild-type alpha-amylase at 60 degrees C but was over twofold greater at 5 degrees C. This effect could be ascribed to a decrease in the activation enthalpy by 32%. The mutation to Asp or Lys altered the pH/activity profile concomitant with possible changes in the ionization state of the groups introduced. These results show the feasibility of altering and possibly improving the enzyme activity by mutagenesis of residues near the catalytic groups. PMID- 8436144 TI - Role of sugar chains in the in-vitro activity of recombinant human interleukin 5. AB - The structures of O-linked sugar chains of recombinant human interleukin 5 (rhIL 5) produced by Chinese hamster ovary cells were determined employing high performance anion-exchange column chromatography under high pH conditions. The core sequence was elucidated to be Gal beta 1-->3-GalNAc by its susceptibility to endo-alpha-N-acetylgalactosaminidase and sialic acid linkages were determined using sialidases of different specificities. To investigate the role of sugar chains in the in-vitro activity of rhIL-5, it was digested with various glycosidases. While removal of N-linked sugar chains resulted in 2.8-fold increase of the activity, de-O-glycosylated rhIL-5 showed 10-fold higher activity than intact rhIL-5, suggesting that the presence of O-linked sugar chains suppresses the activity more effectively than that of N-linked chains. While incubation of de-N-glycosylated rhIL-5 at 70 degrees C for 30 min decreased the activity, intact and de-O-glycosylated rhIL-5 lost little activity, suggesting that N-linked sugar chains contributed to the thermostability of the molecule. PMID- 8436145 TI - Molecular cloning and nucleotide sequence of the gene encoding a H2O2-forming NADH oxidase from the extreme thermophilic Thermus thermophilus HB8 and its expression in Escherichia coli. PMID- 8436146 TI - Morphine-sparing effect of diclofenac in cancer pain. AB - The effectiveness of diclofenac 50 mg t.i.d. as additive treatment to parenteral patient-controlled administration therapy (PCAT) with morphine in cancer pain has been investigated in a double-blind study. In the fifteen patients who completed the study, morphine i.v. was titrated to optimal pain relief over 5 days. The mean total morphine consumption was significantly reduced during diclofenac administration (82.8 mg morphine per day) compared to placebo (95.0 mg morphine per day). The reduction in mean morphine consumption during active treatment with diclofenac was independent of the initial dose of self-titrated morphine. Pain, self-assessed according to VAS, tended to be lower during the diclofenac period, although the difference did not reach statistical significance. No adverse events were recorded among the 15 patients who completed the study. The present findings show that a non-steroidal anti-inflammatory agent, such as diclofenac, has a morphine-sparing effect in morphine-treated patients with cancer pain. PMID- 8436147 TI - The penetration of ciprofloxacin into bronchial mucosa, lung parenchyma, and pleural tissue after intravenous administration. AB - We have studied the concentrations of ciprofloxacin in serum, bronchial mucosa, lung parenchyma, and pleural tissue after a single intravenous dose of 200 mg in 20 patients subjected to lung surgery. The concentrations of ciprofloxacin in the tissues exceeded that in the serum by 3-fold to 7-fold: serum 0.6 micrograms.ml 1, bronchial mucosa 1.9 micrograms.g-1, lung parenchyma 3.4 micrograms.g-, and pleural tissue 1.7 micrograms.g-1. The achievable concentrations of ciprofloxacin in the tissues of the lower respiratory tract are above the MICs for most lung pathogens. PMID- 8436148 TI - Enalapril versus atenolol in the treatment of hypertensive smokers. AB - A randomised crossover study has been done to compare the antihypertensive efficacy of enalapril and atenolol in 45 smoking, hypertensive men. Treatment was started with enalapril 20 mg/d or atenolol 50 mg/d and, if necessary, the doses were doubled after 4 weeks to achieve a sitting diastolic blood pressure < or = 95 mm Hg, after which hydrochlorothiazide was added, if necessary. Both drugs lowered blood pressure significantly. However, enalapril was more efficient in lowering both systolic and diastolic blood pressure; the mean difference was significant after both 4 and 8 weeks in the sitting systolic (11.6 mm Hg and 7.9 mm Hg) and diastolic (3.3 mm Hg and 3.0 mm Hg) pressures and in the erect systolic pressures (8.2 mm Hg and 7.2 mm Hg), and after 8 weeks in the supine systolic pressure, too (8.9 mm Hg). The effect on enalapril was especially marked in moderate (< 20 cigarettes/day) smokers. The need for diuretics was also significantly less in the enalapril group. It appears that angiotensin-converting enzyme inhibitors may be superior to beta-adrenoceptor blockers in the treatment of hypertensive smoking patients. PMID- 8436149 TI - Effects of small doses of bisoprolol on blood pressure and lipoprotein concentrations in hypertensive patients. AB - The effects of bisoprolol 2.5 and 5 mg per day on blood pressure, and lipoprotein and apolipoprotein concentrations were compared in 18 newly detected hypertensives in a double-blind, crossover study. All treatment results were related to the values at the end of a four-week placebo run-in period. Each of the two following treatment periods lasted for 3 months. The systolic and diastolic pressures in the supine position were reduced by 19.5/11.7 mm Hg and 14.6/10.4 mm Hg by 2.5 and 5 mg bisoprolol per day, respectively, with no significant difference in effect. Supine heart rate was reduced by 4.7 and 8.2 beats.min-1, respectively, (P = 0.0517 for different effects). The cholesterol concentration in low-density (LDL) and high-density (HDL) lipoproteins was reduced during both regimens, by about 0.3 and 0.1 mmol.l-1, respectively, difference not significant. Triglyceride concentrations were not significantly affected during either regimen. We conclude that, in this study population, treatment with bisoprolol 2.5 mg per day was equally effective as 5.0 mg per day in reducing blood pressure. The effects on lipoprotein concentrations were small and included an unexpected reduction in LDL-cholesterol concentration. A low dose of a highly selective beta-adrenoceptor blocker like bisoprolol appears to retain the blood pressure reducing capacity and has lost most of the unfavourable effects on lipoproteins characteristic of higher doses. PMID- 8436150 TI - Antihypertensive effect of once daily sustained release isradipine: a placebo controlled cross-over study. AB - To evaluate the magnitude and duration of the antihypertensive effect of sustained release (SRO) isradipine, 37 uncomplicated essential hypertensive patients (diastolic blood pressure 100-115 mm Hg after a one month run-in on placebo) were randomised to receive, according to a double-blind cross-over design, isradipine SRO 5 mg once daily and the corresponding placebo for 1 month. At the end of each treatment period, sitting blood pressure and heart rate were measured immediately before and every hour for 6 h after the last dose. Thirty four patients [16 m, age 54 (7) y] completed the study. As compared to randomised placebo, isradipine SRO significantly reduced the systolic (SBP) and diastolic (DBP) blood pressure. Absolute DBP decrements versus placebo peaked 6 h after dosing (-8.8 mm Hg) and were not significantly lower (-8.2 mm Hg) at the end of the dose interval. At the same times, the absolute decrements in SBP were -9.8 mm Hg and -9.7 mm Hg, respectively. DBP was normalised in 19 patients (56%) at peak and in 17 (50%) at trough time. The trough to peak efficacy ratio in patients with peak DBP < or = 90 mm Hg was 70%. Heart rate was slightly increased by isradipine SRO. Adverse effects monitored with a check-list occurred in 8/36 patients (22%) on isradipine SRO and in 4/35 (11%) on randomized placebo. The data suggest that isradipine SRO is an effective antihypertensive drug, with a trough to peak efficacy ratio supporting once daily administration in most mild to moderate essential hypertensives. PMID- 8436151 TI - The haemodynamic effects and pharmacokinetics of intravenous nicorandil in healthy volunteers. AB - We have studied the effects of intravenous nicorandil, a mixed arterial and venous vasodilator, in 48 healthy volunteers. Nicorandil (20, 28, 39, 54, 74, 103, 144, or 200 micrograms.kg-1) or placebo were given over 5 min to subjects supine (16 subjects, 2 doses) or sitting (32 subjects, 1 dose) in a single-blind crossover design. Electrocardiographic intervals, blood pressure, and heart rate were measured before and for 8 h after dosing. Blood and urine safety laboratory studies were also performed before and after dosing. All intravenous infusions of nicorandil and placebo were well tolerated and there were no clinically important safety concerns. The most frequent adverse event after nicorandil was headache (24 events by 19 subjects), although its occurrence was not strictly dose related. One subject experienced transient symptomatic hypotension (144 micrograms.kg-1). Mean plasma nicorandil concentrations were dose-related and fell with a half-life of 0.7 to 1.2 h. Systemic clearance and volume of distribution tended to decrease as dose increased. Sitting subjects showed marginally lower (< 20%) systemic clearances and larger values of Cmax and AUC. Nicorandil produced dose-related reductions in blood pressure, with consistent statistically significant differences from placebo after the 144 and 200 micrograms.kg-1 doses. The falls in blood pressure were greater for diastolic pressure and in this supine position. At 200 micrograms.kg-1, the mean falls in systolic/diastolic pressures (mm Hg) during the first hour were 10.9/14.7 supine and 6.1/9.1 sitting; systolic pressure returned to baseline after 8 h and diastolic pressure after 4 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8436152 TI - Systemic and renal haemodynamic effects of angiotensin converting enzyme inhibition by zabicipril in young and in old normal men. AB - Zabicipril is a recently introduced angiotensin converting enzyme (ACE) inhibitor, which has been observed in experimental animals to increase diuresis, natriuresis, glomerular filtration rate (GFR) and renal plasma flow (RPF). We have investigated the acute effects of zabicipril on systemic and renal haemodynamics in two groups of 8 sodium-replete normal men, aged 23 to 30 y and 65 to 74 y. Zabicipril 0.5 mg, 1 mg or 2.5 mg and a placebo were administered orally, at one week intervals, in a random order and in a double blind fashion. Haemodynamic measurements were performed at base line and every hour for 4 hours after intake of drug or placebo. Cardiac output (Q) was measured by Doppler echography, and RPF and GFR by the constant infusion technique using I123 iodohippurate and Cr51 EDTA, respectively. In the young men zabicipril did not affect Q, heart rate (HR), systemic arterial pressure (AP) or GFR, but it did increase RPF at the 4th hour after the highest dose (from 540 to 653 ml.min-1.m 2). In the old men zabicipril had similar actions, but the effect of the highest dose on RPF (from 355 to 415 ml.min-1.m-2) was less marked than in the young men. In the young and old men the inhibition of ACE peaked at about of 90% or more from the 2th to the 4th hour after the highest dose of zabicipril. We conclude that, in normal men, zabicipril increases the renal fraction of cardiac output in the absence of a concomitant change in systemic haemodynamics. This specific effect of zabicipril on the kidney may be less important with advancing age. PMID- 8436153 TI - Cutaneous blood flow changes and weal induced by intradermal bradykinin following pretreatment with indomethacin and captopril. AB - The effects of indomethacin and captopril on local cutaneous blood flow changes and weal induced by intradermal injections of bradykinin were assessed in two randomised, double-blind, placebo-controlled studies in healthy volunteers. Alterations in cutaneous blood flow were estimated by laser Doppler flowmetry (LDF) and erythema area. LDF output, erythema area and weal volume increased with incremental bradykinin dose. Single doses of indomethacin 25 mg and 75 mg did not affect these cutaneous responses compared with placebo. Captopril 25 mg significantly potentiated the increase in local cutaneous blood flow measured by LDF, but not erythema area, and weal volume induced by bradykinin. The effects of the combined treatment of indomethacin 75 mg and captopril 25 mg were not significantly different from those due to captopril alone. The enhanced cutaneous effects of bradykinin following administration of captopril are in keeping with effective kininase II inhibition in the tissues. Cyclo-oxygenase products release does not appear to contribute to the cutaneous actions of bradykinin nor the potentiation of these responses by captopril. PMID- 8436154 TI - Lack of tolerance of headache and radial artery diameter during a 7 hour intravenous infusion of nitroglycerin. AB - Nitroglycerin-(NTG)-induced headache and dilatation of the radial artery were followed in a double blind, randomized, placebo-controlled, cross-over study in 6 healthy volunteers. NTG 0.5 microgram.kg-1 x min-1 or saline were infused i.v. for 7 h, and subsequently the infusion rate was doubled for 10 min. The radial artery diameter was measured repeatedly with high frequency ultrasound and pain was scored using a 10 point verbal scale. After 5 min of NTG infusion both headache and the arterial diameter differed significantly from baseline, and no further significant change occurred. The intensity of the headache was mild to medium (median headache score 3, range 1-7). The mean dilatation of the radial artery was 36%. The dilatation in each individual, was stable over time, both during NTG and placebo, and it did not change with the double infusion rate. The headache score in each individual was more fluctuant. No tolerance either to the NTG-induced headache or arterial dilatation was observed. PMID- 8436155 TI - Lack of effect of cimetidine on cigarette smoking. AB - The efficacy of cimetidine as a treatment that could reduce smoking in heavily dependent smokers has been determined. In a randomised, double-blind, double crossover experiment, 43 heavy smokers were divided into two groups, one receiving cimetidine 400 mg orally three times a day, and the other receiving placebo for two weeks followed by the alternative treatment (placebo or cimetidine). No significant difference in the mean alveolar carbon monoxide, nicotine or cotinine levels was found between the two treatment groups compared to baseline. Since the alveolar carbon monoxide level reflects the intensity of smoking behaviour, the results suggest that no change in smoking behaviour occurred in the subjects. Contrary to our previous findings that cimetidine decreased the total body clearance of nicotine by 30% in a population of non smokers, in the heavily dependent smokers, cimetidine did not appear to alter nicotine elimination. One possible explanation for the discrepancy is that tobacco smoking is known to induce nicotine metabolism and the induction might have offset any effect of cimetidine on nicotine elimination. Cimetidine does not appear to be a useful treatment leading to a reduction or cessation of cigarette smoking. PMID- 8436156 TI - A comparison of the effects of single doses of amoxapine and amitriptyline on autonomic functions in healthy volunteers. AB - We have studied the effects of single oral doses of amoxapine (100 mg and 200 mg), amitriptyline (50 mg and 100 mg), and placebo on some autonomic functions in ten healthy volunteers, using a balanced double-blind crossover design. Amitriptyline significantly reduced salivation and it significantly attenuated both miosis evoked by locally applied pilocarpine and sweat secretion evoked by locally applied carbachol. Amoxapine did not significantly alter any of these measures. Neither treatment significantly altered the pupillary light reflex (latency, amplitude, or 75% recovery time). Resting pupil diameter was significantly reduced by the higher dose of amoxapine but was not affected by the other treatments. The higher dose of amoxapine significantly increased supine systolic blood pressure, but did not affect heart rate or diastolic blood pressure; amitriptyline had no effect on any of these cardiovascular measures. These results confirm the antimuscarinic effects of amitriptyline in man, but provide no evidence for antimuscarinic effects of amoxapine. PMID- 8436157 TI - Influence of debrisoquine hydroxylation phenotype on the pharmacokinetics of mexiletine. AB - Marked interindividual variation has been observed in the pharmacokinetics of the antiarrhythmic agent mexiletine. The fact that its urinary excretion is dependent on urinary pH may account, in part, for such variation. The influence that genetic differences in hepatic metabolism of the debrisoquine-type may have on mexiletine pharmacokinetics was considered in this study. The pharmacokinetics and urinary excretion of mexiletine (250 mg administered intravenously) were investigated in 5 rapid extensive metabolisers (EM), 5 slow EM and 5 poor metabolisers (PM) of debrisoquine, under conditions of controlled urinary pH. Mexiletine disposition kinetics was found to be altered in PM individuals. These subjects showed higher total area under the curve (AUC), (15.7 versus 8.16 micrograms.h.ml-1) prolonged elimination half-lives (in serum and urine) (serum: 18.5 versus 11.6 h, urine: 19.2 versus 11.7 h) and lower total clearance values compared with EM (216 versus 450 ml.min-1). In this respect, slow EM individuals generally presented intermediate values of those pharmacokinetic parameters. A higher incidence of adverse-effects was also observed among slow EM and PM subjects. It is concluded that genetic differences in mexiletine oxidation of the debrisoquine-type have an influence on its observed pharmacokinetic variability. The clinical consequences are discussed. PMID- 8436158 TI - The effect of benzbromarone on allopurinol/oxypurinol kinetics in patients with gout. AB - The objectives of this study were to establish if, and to what extent, benzbromarone affects allopurinol/oxypurinol kinetics, and to compare the uric acid lowering capabilities of Allomaron (allopurinol 100 mg plus benzbromarone 20 mg) with the effects of allopurinol alone in patients with confirmed gout. We studied 14 adult men in an open randomized cross-over study. After a 14 day run in period with Zyloprim (2 x 100 mg allopurinol tablets in the morning), the patients were randomly allocated to morning doses of either Allomaron (2 tablets) or Zyloprim (2 tablets). Seven days later cross-over was effected and the alternative treatment was taken for a further 7 days. On days 7 and 14 the patients came into hospital and venous blood samples were taken over 24 h for allopurinol and oxypurinol assays by HPLC. Serum uric acid was determined on days -14, 1, 7, and 14. Benzbromarone lowered plasma oxypurinol concentrations (Allomaron/Zyloprim mean ratio of AUC0-->24 was 59%; 95% confidence interval 54 64%), but did not affect plasma allopurinol concentrations. Despite this pharmacokinetic interaction of benzbromarone with allopurinol, resulting in lower plasma concentrations of oxypurinol, Allomaron was superior to allopurinol alone in lowering serum uric acid, probably because of the added uricosuric effect of benzbromarone. PMID- 8436159 TI - Differential effects of beta-adrenoceptor partial agonists in patients with postural hypotension. AB - The central haemodynamic effects of pindolol and xamoterol have been investigated in patients with postural hypotension. Pindolol is a non-selective beta adrenoceptor partial agonist, whereas xamoterol is beta 1-selective and possesses a higher degree of agonist activity. The study comprised 16 patients with postural hypotension of different aetiologies. Blood pressure, heart rate and stroke volume were measured in the supine and head-up tilted positions. Left ventricular ejection fraction (LVEF) was measured in the supine position, and vascular resistance, left ventricular volume, and left ventricular contractility were derived. Pindolol and xamoterol were administered intravenously in incremental doses to reach total doses of 0.02 and 0.20 mg.kg-1, respectively. Pindolol showed beta-adrenoceptor antagonistic effects in the supine position through decrements in heart rate from 70 to 66 beats.min-1 and LVEF from 0.57 to 0.52, and reduced mean arterial blood pressure from 103 mm Hg to 93 mm Hg. Xamoterol showed beta-adrenoceptor agonistic effects in the supine position through increments in heart rate from 72 to 90 beats.min-1 and LVEF from 0.58 to 0.66, and raised mean arterial blood pressure from 108 to 123 mm Hg. It is concluded that the degree of agonist activity of a beta-adrenergic agent is of importance if it is given to a patient with postural hypotension. PMID- 8436160 TI - Kinetics of thiamin and thiamin phosphate esters in human blood, plasma and urine after 50 mg intravenously or orally. AB - The concentrations of thiamin and thiamin monophosphate and diphosphate in plasma and whole blood samples were assessed in six healthy subjects for 12 h and in urine for 24 h following an IV and PO bolus dose of 50 mg thiamin HCl. Unphosphorylated thiamin increased rapidly in plasma after IV administration and then decreased to its initial value within 12 h in all but one subject; the half life was 96 min. Thiamin mono and -diphosphate increased moderately (56%), and decreased slowly; the half-life of diphosphate was 664 min. Within 24 h, 53% of the administered dose was recovered in the urine, indicating a restricted distribution. After oral administration, the peak thiamin concentration in plasma was reached after 53 min and the concentration then had increased to 179% of its initial value. The elimination half-life was 154 min, and only 2.5% of the given dose was recovered in the urine. The relative bioavailability of thiamin was 5.3%. A moderate amount of the administered thiamin was stored in blood. Other body tissues must play an important part, therefore, in the distribution of thiamin. PMID- 8436161 TI - Nonlinear kinetics of threo-methylphenidate enantiomers in a patient with narcolepsy and in healthy volunteers. AB - We have studied the pharmacokinetics of methylphenidate enantiomers after the oral administration of different doses of racemic methylphenidate to one patient with narcolepsy and to four healthy volunteers. The plasma concentrations of (+) methylphenidate were much higher than those of (-)-methylphenidate after each dose in all subjects. In the patient the oral clearance (CL/f) of (+) methylphenidate fell 3-fold and the area under the concentration-time curve (AUC) rose 7-fold when the dose was increased from 20 to 40 mg (from 0.27 to 0.53 mg.kg 1), in spite of the relatively constant terminal half-life of 2.6-2.7 h. Similar dose-dependency was also observed in the healthy volunteers in the dose range of 10-60 mg (0.12-0.77 mg.kg-1). The mean value of CL/f for the 40 mg dose was significantly lower than that for the 20 mg dose. The mean AUC of the (+)-isomer corrected to a dose of 10 mg increased significantly between the 20 mg and 40 mg doses. In the urine (+)- and (-)-ritalinic acid were excreted for 48 h after each dose as 32-37% and 34-40% of the dose respectively. The mean total recoveries (sum of enantiomers of methylphenidate and its metabolite, ritalinic acid) in the urine were relatively constant (63-78% of the doses), suggesting that the changes in AUC with dose may not be due to a change in the intestinal absorption of racemic methylphenidate. We conclude that the nonlinear kinetics of (+) methylphenidate may be due to saturation of its presystemic elimination. PMID- 8436162 TI - Lack of effect of magnesium-aluminium hydroxide on the absorption of theophylline given as a pH-dependent sustained release preparation. AB - Antacids can modify the pharmacokinetic parameters of sustained-release preparations of theophylline by changing the gastric pH. Though this has been studied with various theophylline/antacid combinations, the specific preparations investigated here have not previously been tested. The objective of the study was to assess any change in the availability of theophylline from a sustained-release preparation (SR), induced by the coadministration with an antacid. The study was designed as a double-blind randomized crossover trial in the Pneumology Departments of three general hospitals. Fifteen patients were studied. They all had stable asthma treated with theophylline and no major organ failure or gastro intestinal lesions requiring the use of antacids. The antacid (aluminium hydroxide 800 mg and magnesium hydroxide 800 mg), or placebo, tid, was added to a stable regimen of theophylline SR bid, for 4 days, in crossover fashion. Plasma theophylline concentrations were measured before and 1, 2, 3, 4, 6, 8, 10, 12, 16 and 24 h after the morning dose of Armophylline on the fourth day of each treatment period; the maximum plasma concentration (Cmax), and time to Cmax (tmax) were noted, and the area under the 24-h time-concentration curve (AUC0-24) and mean plasma concentration (Cmean) were computed. Peak expiratory flows on the same day, before and 3, 6 and 12 h after the morning dose of Armophylline were also measured. There was no change in any of the parameters studied. The addition of the antacid to theophylline, each given according to standard clinical practice, did not modify the pharmacokinetics of the latter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8436163 TI - Acute effects of cicletanine in angina pectoris. AB - The anti-anginal properties of single doses of a new anti-hypertensive drug, cicletanine, were investigated in a double-blind, randomised, balanced, crossover comparison with placebo in sixteen patients with chronic stable angina pectoris. All subjects underwent treadmill exercise 2 h after drug administration and 24 h ambulatory ECG monitoring with ST scanning. Although there were significantly fewer episodes of ST depression on ambulatory monitoring after cicletanine, total exercise duration and time to 1 mm ST depression were unchanged. This report provides little evidence of an acute anti-anginal effect of cicletanine but longer term studies may be indicated to further evaluate this drug's potential role in the management of angina pectoris. PMID- 8436164 TI - Minor and clinically non-significant interaction between toloxatone and amitriptyline. AB - The possibility of a pharmacokinetic interaction between amitriptyline and toloxatone (a new MAOI-A) has been studied in 17 depressed in-patients. Amitriptyline and its demethylated and hydroxylated metabolites in blood and urine were measured at steady state after the administration of amitriptyline with and without toloxatone in steady state. The metabolic status of patients was determined using the dextromethorphan phenotyping test. There was only a minor pharmacokinetic interaction between amitriptyline (AMT) and toloxatone, with a small increase in the AMT/NT (nortriptyline) plasma ratio: 0.68 before and 0.78 after toloxatone. The urinary excretion and plasma levels of AMT and its metabolites were not affected by the co-therapy. Three of the patients were poor metabolisers, but this did not predict the magnitude of the drug interaction. The interaction does not justify plasma level monitoring of amitriptyline as the change in pharmacokinetics was so small. PMID- 8436165 TI - Intestinal T lymphocytes in the chicken express an integrin-like antigen. AB - We report the characterization of a molecule recognized on chicken T cells by the murine A19 monoclonal antibody that was generated by immunization with intestinal intraepithelial lymphocytes. Immunofluorescence analysis indicated that both alpha beta and gamma delta T cell subpopulations in the intestine express the A19 antigen, but natural killer cells and B cells do not. The A19-marked T cells were preferentially localized in the intestinal epithelium and less frequently in the underlying lamina propria. T cells appearing in the intestine during embryonic life were A19 negative but acquired the antigen within the first few days after hatching. Although rarely found on cells in non-intestinal tissues at any age, very late expression of the A19 antigen could be induced by concanavalin A stimulation of splenic and circulating T cells. Transforming growth factor beta 1 enhanced this induction of A19 expression. The A19 molecules expressed by intestinal T cells and activated splenic T cells were biochemically identical, consisting of a multi-molecular complex of proteins with approximate M(r) of 205, 145 and 75 kDa under nonreducing conditions and 120, 90 and 28 kDa under reducing conditions. The characteristics of this multimolecular complex and its differential expression suggest that the A19 antigen is a member of the integrin family which may function in the retention of intestinal lymphocytes. PMID- 8436166 TI - Transcriptional diversity at the duplicated human CD8 beta loci. AB - In order to understand the structural organization of the human CD8 beta locus, genomic clones containing CD8 beta sequences were isolated and analyzed. Physical linkage of these clones with the CD8 alpha locus using pulsed-field electrophoresis revealed a duplication of the CD8 beta locus. CD8B-1 lies 35 kb upstream from the CD8 alpha locus and contains eight exons, including four alternatively spliced cytoplasmic exons. The CD8B-2 gene contains six exons and is at present unlinked to CD8B-1. Analysis of sequences upstream to the leader exon of the CD8B-1 and CD8B-2 genes revealed a GC-rich promoter which lacks canonical "CCAAT" and "TATA" motifs, but which has sites for multiple transcriptional activators and three additional elements which are conserved in the murine CD8 beta promoter. Seven unique CD8 beta cDNA isoforms were isolated and characterized, which derive from alternative splicing of the transmembrane and/or cytoplasmic exons. Three cDNA are membrane spanning, while the remaining four isoforms lack a transmembrane region and are potentially secreted. These transcripts are differentially expressed in the thymus and in the periphery. Transfection experiments in murine fibroblasts confirmed that the membrane CD8 beta isoforms could be expressed as heterodimers with the CD8 alpha chain. The regulated expression of multiple CD8 beta cytoplasmic isoforms and their potential role in T lymphocyte signal transduction is discussed. PMID- 8436167 TI - T cell regulation of collagen-induced arthritis in mice. II. Immunomodulation of arthritis by cytotoxic T cell hybridomas specific for type II collagen. AB - Injection of native type II collagen (CII) to susceptible strains of mice (H-2q) induces a rheumatoid arthritis-like disease. To study the role of CD8+ T cells in the collagen-induced arthritis (CIA), we generated CII-specific T cell hybridomas by fusion of cells from arthritic C3H. Q mice and an AKR thymoma. Two hybrid clones (P3G8 and P2D9) were selected for their ability to lyse syngeneic CII pulsed macrophages and recognize different antigenic epitopes in association with Kq molecules. When these T cell clones were irradiated and inoculated into (C3H.Q x AKR)F1 mice 21 days prior to priming with native CII/complete Freund's adjuvant, the incidence and the duration of CIA were significantly reduced in comparison to groups receiving saline or control T cell hybridoma. Furthermore, both anti-CII T cell hybridomas were able to attenuate CIA in highly susceptible inbred strains of mice and this suppression was antigen and disease specific. The protective activity seems to require intact cells as neither membrane fractions nor cytosolic preparations of the hybridoma T cells retained the vaccinating activity. Most importantly, one of the hybrid clones (P3G8) had a therapeutic effect on CIA since its administration to arthritic DBA/1 mice on day 30 after priming down-regulated the ongoing disease. Taken together, these findings suggest that anti-CII cytotoxic T cell clones can vaccinate against CIA and even reverse the disease. PMID- 8436168 TI - Differential cytokine expression in acute and chronic murine graft-versus-host disease. AB - The relationship between acute and chronic graft-versus-host disease (GVHD) is not well understood. While both syndromes appear to result from recognition of host antigens by donor T cells, their pathological changes differ markedly. In light of the recent concept that helper T cells (Th) may be divided into two types based on their cytokine secretion profile and their ability to mediate cellular (Th1) or humoral (Th2) immunity, and considering the inflammatory nature of acute GVHD and the occurrence of significant B cell activation in chronic GVHD, we hypothesized that acute and chronic GVHD may be associated with differential cytokine production by activated T cells. To evaluate this hypothesis, we assessed expression of a range of cytokines in (C57BL/6 x DBA/2)F1 (B6D2F1) recipients of C57BL/6 (acute GVHD), DBA/2 (chronic GVHD) or B6D2F1 (control) spleen cells. The results reported here indicate that a wide range of cytokines, including interleukin (IL)-4, IL-10, interferon-gamma, tumor necrosis factor beta and macrophage inflammatory protein-1 alpha, are indeed differentially expressed in acute and chronic GVHD and support the concept that the pathology peculiar to acute or chronic GVHD may arise due to differential cytokine expression by activated T cells. PMID- 8436169 TI - Cross-reactivity among evolutionarily distant major histocompatibility complex class I molecules (HLA-B27 and H-2Kk) revealed by xenoreactive T lymphocytes. AB - A set of mouse HLA-B27-reactive cytotoxic T lymphocyte clones were found to recognize the HLA-B27 molecule in an H-2-unrestricted manner, i.e. independently of any mouse major histocompatibility complex (MHC) molecule. The reactivity patterns of these clones on HLA-B27 variants (positive only on HLA-B*2702 and HLA B*2701) allowed the identification of residues N77 and A81 of the HLA-B27 molecule as important for their reactivity. The location of these residues in the peptide-binding groove (specificity pocket F) suggested that the reactivity of the clones is dependent on HLA-B27-bound peptide(s). However, several other class I molecules sharing these residues (N77 and A81) were not recognized, indicating that other residues might also be involved. One of the clones was found to display an interesting cross-reactivity with allogeneic H-2Kk molecules, sharing N77 and A81 with HLA-B*2702. Sequence comparison suggested the involvement of residue H9, located in specificity pocket B of the peptide-binding groove, and revealed some similarity of pockets B in HLA-B27 and H-2Kk. The structural basis of such T cell-mediated MHC cross-reactions across species barriers is discussed. PMID- 8436170 TI - Position 71 in the alpha helix of the DR beta domain is predicted to influence peptide binding and plays a central role in allorecognition. AB - Despite all the structural and functional data that have been accumulated regarding major histocompatibility complex (MHC) class II molecules during recent years, the relative contribution of putative T cell receptor (TcR)-contacting residues and peptide-binding MHC polymorphisms to MHC-restricted and allospecific T cell responses remains a point of contention. Some authors emphasize the importance of direct interaction between the allospecific TcR and polymorphic MHC residues whereas other emphasize the role of naturally processed MHC-bound peptides. We have previously described a new HLA-DRB1 allele: DR BON (DRB1*0103). This gene differs from DRB1*0101 by six base pairs clustered in the third variable region of the second exon leading to three amino acid changes at positions 67, 70 and 71 of the beta chain of the HLA-DR molecule. To define the respective role of these residues in allorecognition, we have performed site directed mutagenesis on the DRB1*0103 allele to create six mutants which are intermediary between the DR BON and the DR1 alleles. These mutant cDNA were expressed in mouse fibroblasts and the transfectants with the highest expression of class II molecules were used as stimulators for a panel of ten anti-DR BON and five anti-DR1 alloreactive T cell clones. We demonstrate that the residue at the peptide-binding position 71 is of paramount importance in the alloresponse of these clones. In addition some clones were sensitive to amino acid substitution at the TcR-contacting position 70, while substitution at position 67 affects very few clones. The dominance of residue 71 was also observed with an influenza hemagglutinin-specific HLA-DR BON-restricted T cell line. PMID- 8436171 TI - Only a small proportion of splenic B cells in adults are short-lived virgin cells. AB - A cohort of newly produced virgin B cells was followed from the marrow to the spleen of non-immunized clean rats, which showed minimal antigen-driven proliferation of B cells in their spleens. The progenitors of this cohort of virgin cells were labeled in vivo over 12 h with the thymidine analogue 5-bromo 2'-deoxyuridine (BrdUrd) and their non proliferating progeny left the marrow 2-3 days later. This coincided with the arrival of labeled B cells in the red pulp and T zones of the spleen. These appear to be short-lived as few remained a week after the label was given. The short-lived newly produced virgin B cells can only comprise a minority of splenic B cells, for it is shown that only 20% of splenic B cells are found in the red pulp and T zone. It is calculated that newly produced virgin B cells are likely to make up between 5% and 10% of splenic B cells. In the marginal zones and follicular mantle respective medians of 3.3% and 1.8% were already labeled at 1 day from the start of the BrdUrd pulse. The appearance of these cells seems likely to result from antigen-driven B cell proliferation outside the marrow, for labeled virgin B cells have not started to leave the marrow at this stage. During day 2 and 3 the proportion of labeled follicular mantle B cells rose to 3.4%, which might in part reflect the recruitment of newly produced virgin B cells to the pool of recirculating follicular B cells. After day 3 in the follicles and day 1 in the marginal zones the proportion of labeled cells did not vary significantly through day 7. This appears to confirm the comparative longevity of the cells in these zones, which contain 80% of the non-proliferating splenic B cells of adult rats. PMID- 8436172 TI - A human myeloma IgA with a hybrid heavy chain resulting from putative somatic gene conversion. AB - A human monoclonal IgA1-IgA2 lambda hybrid molecule was detected in a myeloma patient homozygous for the A2m(1) allotype during a systematic study of monoclonal IgA with subclass-specific monoclonal antibodies (mAb) and the lectin jacalin. This monoclonal immunoglobulin (GAU) reacted with both, although not with all, anti-alpha 1 and anti-alpha 2 mAb. Its heavy (H) chain contained an alpha 1 hinge region as shown by jacalin reactivity, the presence of disulfide linked H and light chains in spite of its belonging to the IgA2m(1) allotype and amino acid composition of the isolated hinge region. The complete sequence of the H chain was deduced from that of complementary DNA clones from bone marrow cells. The CH1 domain, hinge region and beginning of the CH2 domain and the membrane peptide were encoded by the alpha 1 gene, with an insertion of an alpha 2m(1) gene sequence accounting for the end of the CH2 and part or all of the CH3 domain (sequence identity between the two normal genes precludes a precise definition of breakpoints). The region of the 5' recombination site included a repeat of a six base pair sequence which might play a role in the genetic exchange. The GAU hybrid alpha gene was undetectable in the patient's genomic DNA from polymorphonuclear cells. The genetic event which occurred at the level of the proliferating plasma cell clone is most likely to be a gene conversion. PMID- 8436173 TI - Dissection of human Langerhans cells' allostimulatory function: the need for an activation step for full development of accessory function. AB - In the present study, we analyzed the mechanism by which human Langerhans cells (LC), the dendritic cells (DC) from epidermis, support the induction of a primary allogeneic T cell response. We reported that paraformaldehyde (PF) fixation completely abrogated the stimulatory property of freshly isolated LC, although the level of major histocompatibility complex (MHC) class II antigen (Ag) expression was unaltered by the fixative. Addition of either interleukin (IL)-1 beta and/or IL-6, during the mixed epidermal cell lymphocyte reaction, failed to restore the proliferative response. By contrast, when human LC were incubated for 3 days in culture medium before fixation, they retained a low but significant allostimulatory capacity. Trypsin treatment of incubated LC before fixation did not impair their function, suggesting that stimulatory activity by fixed incubated LC did not merely reflect a repair of LC membrane after trypsin trauma suffered during epidermal cell (EC) isolation. More interestingly, we found that addition of interferon-gamma during LC incubation mediated an enhanced allostimulatory activity by the PF-fixed LC. Acquisition of allostimulatory property by in vitro activated and fixed LC did not correlate with increased MHC class II Ag expression at the cell surface. By contrast, we showed that ICAM-1 Ag expression by human LC is involved in this maturation process. Finally, we found that once human LC have been activated, IL-1 beta, but not IL-6, could serve as a costimulatory factor in the primary allogeneic T cell response. In conclusion, the data suggest that human LC accessory function is not constitutive but requires an activation step which can be provided by interferon-gamma during LC-T cell interaction. PMID- 8436174 TI - V kappa gene segments rearranged in chronic lymphocytic leukemia are distributed over a large portion of the V kappa locus and do not show somatic mutation. AB - The structure of the human V kappa locus has been thoroughly investigated, but how the germ-line V kappa gene segment repertoire is actually sampled in kappa chain gene rearrangements is not known. In order to begin to answer this question we have polymerase chain reaction (PCR) amplified the rearranged V kappa genes from 26 kappa-expressing cases of chronic lymphocytic leukemia (CLL), followed by cloning and sequencing of the PCR product. All four V kappa gene families were represented amongst rearranged genes. In 25 out of 32 cases, the sequence of the rearranged gene matches perfectly that of 1 of 11 different known germ-line V kappa genes, indicating that no somatic mutation has occurred. Of the remaining 7 rearranged V kappa genes, 4 differ from known germ-line genes by only one or two amino acid residues; and 3 differ from each other and from all known sequences by 5 or more residues, suggesting that somatic mutation has occurred in these 3 cases. We conclude that: (a) in at least three-quarters of cases the rearranged genes are unmutated; (b) there is preferential usage of individual V kappa genes but not of V kappa gene families; and (c) the V kappa genes used are widely dispersed in the V kappa locus. PMID- 8436175 TI - Human interleukin-5 induces staphylococcal A Cowan 1 strain-activated human B cells to secrete IgM. AB - Studies on the role of human interleukin (IL)-5 in B cell growth and differentiation have yielded conflicting results. To clarify this issue, we studied the role of purified recombinant IL-5 on activated human B cells which were depleted of T cells and adherent cells. Human IL-5 augments IgM secretion, but not IgG or IgA secretion of purified human B cells activated with staphylococcal A Cowan 1 strain (SAC). However, the period of B cell activation with SAC is critical for the B cell to respond to IL-5. After 24 h of SAC activation, human B cells are responsive to the IL-5 signal, but with longer periods of activation, IL-5 responsiveness diminishes. This may explain some of the previous conflicting results. The IgM enhancement was not seen when B cells were activated with pokeweed mitogen. In addition, human recombinant IL-4 synergized with IL-5 in augmenting IgM secretion by SAC-activated B cells, while IL-5 synergized with IL-2 to augment IgM, IgG and IgA secretion by SAC-activated B cells. As the purified IL-5 was derived from a COS-1 cell supernatant, and COS 1 cells secrete IL-6, we examined whether a polyclonal IL-6 antibody blocked the IgM-enhancing activity of IL-5. IL-6 antibody did not block the IL-5 enhancement of IgM secretion, but a monoclonal antibody to IL-5 inhibited the human IL-5 activity on human B cells. These results demonstrate that human IL-5 augments IgM secretion of SAC-activated human B-cells. In addition, this lymphokine synergizes with IL-4 and IL-2 in supporting Ig secretion. PMID- 8436176 TI - The generation of a humanized, non-mitogenic CD3 monoclonal antibody which retains in vitro immunosuppressive properties. AB - CD3 antibodies are proven immunosuppressants capable of reversing transplant rejection episodes. Their general application has been limited both by their immunogenicity and, in particular, by the "first-dose" cytokine-release syndrome experienced by patients after the initial administration of antibody. We have produced a set of variants of the humanized YTH 12.5 CD3 monoclonal antibody (mAb) (Routledge et al., Eur. J. Immunol. 1991. 21: 2717) bearing different human heavy (H) chain constant regions, with the intention of finding a form of the antibody that is not able to activate T cells. Comparison of the variants having gamma 1, gamma 2, gamma 3 and gamma 4 H chains in a competitive binding assay showed that antibody avidity was not affected by IgG subclass. Using a sensitive indicator of FcR binding activity (the capacity of the CD3 mAb to redirect cytotoxic T cells to kill the monocytic cell line U-937) we demonstrated a functional hierarchy of gamma 1 = gamma 4 > alpha 2 =/> gamma 3 mb >> gamma 2. An aglycosyl version of the gamma 1 CD3 mAb, produced by site-directed mutagenesis (Asn297 to Ala), still had considerable activity in this assay (intermediate to the gamma 1 and alpha 2 CD3 mAb), albeit at a level approximately 10-fold lower than that of the parental gamma 1 form. When we tested their ability to stimulate T cell proliferation in vitro in the presence of 5% human serum, all of the wild type immunoglobulin isotypes were found to be active, although there were T cell donor-dependent variations in the extent of the responses. The aglycosyl gamma 1 mAb was, however, completely non-mitogenic in all of ten donors tested, unless the assay was performed in IgG-free medium. Despite being non-stimulatory, this mAb was also able to inhibit the mixed lymphocyte reaction responses of both naive and primed T cells. Comparison of the gamma 1 and aglycosyl gamma 1 mAb in an experimental mouse model for CD3 mAb-induced cytokine release indicated that removal of the carbohydrate moiety from the gamma 1 constant region reduced the in vivo tumor necrosis factor-alpha response by a factor of at least 16-fold. These data suggest that the aglycosyl gamma 1 CD3 mAb is a promising candidate for immunosuppressive therapy without "first dose" side effects. PMID- 8436177 TI - Limiting dilution analysis of interleukin-2-producing T cells responsive to recall and alloantigens in human immunodeficiency virus-infected and uninfected individuals. AB - Peripheral blood mononuclear cells (PBMC) from individuals who were seropositive for the human immunodeficiency virus type 1 (HIV), and most without symptoms (HIV+) were compared with PBMC from healthy HIV-seronegative (HIV-) individuals for in vitro generated T helper cell (Th) responses. Th function in bulk culture and limiting dilution analysis was assessed by IL-2 production following stimulation with influenza A virus (FLU) or irradiated allogeneic PBMC (ALLO). We observed that the frequencies of FLU- and ALLO-stimulated Th cells were not appreciably different in the PBMC of HIV- individuals, and that they were also not different in the PBMC of those HIV+ individuals who responded to both FLU and ALLO in bulk culture. However, there was a severe drop in the Th frequency to FLU in HIV+ individuals who were unresponsive to FLU but responsive to ALLO by bulk culture. The PBMC of HIV+ individuals who were unresponsive by bulk culture to both FLU and ALLO exhibited a drastic reduction in the Th frequencies for both stimuli. These results demonstrate a concordance between Th functional analysis performed by limiting dilution and bulk culture. The results also indicate that the early selective loss in Th function to recall antigens is not likely to be due simply to a difference in frequencies of FLU- and ALLO-stimulated Th cells present prior to the onset of Th dysfunction. PMID- 8436178 TI - Complement enhances the elimination of soluble aggregates of IgG by rat liver endothelial cells in vivo. AB - In the present study, we have investigated the role of complement (C) and possible C receptors present on rat liver endothelial cells (EC) in the clearance and tissue distribution of soluble aggregates of IgG (AIgG). To study the effect of elimination of AIgG by EC in vivo, Kupffer cell (KC)-depleted rats were used, with or without an intact C system (These rats will be referred to throughout this report as EC-rats.) In EC-rats with an intact C system, clearance of AIgG (2000-3000 kDa, 20-27 IgG molecules/aggregate) occurred in a biphasic manner with a first T 1/2 (T1) of 9.4 +/- 2.3 min and a second T 1/2 (T2) of 44.7 +/- 16.0 min. In EC-rats without an intact C system [cobra venom factor (COVF)-treated group], clearance of AIgG was significantly delayed with a T1 of 25.3 +/- 9.9 min (p < 0.005) and a T2 of 124.5 +/- 18.4 min (p < 0.001). There were less degradation products of AIgG in the circulation in EC-rats treated with COVF as compared to EC-rats with an intact C system. Eight minutes after injection, 27.5 +/- 11.6% of the injected AIgG was found in the livers of EC-rats while 15.1 +/- 3.2% was found in the livers of the COVF-treated group. Double immunofluorescence studies indicated that AIgG in the liver was associated with EC in the rats with an intact C system. Clear deposits of C3 and lesser amounts of C1q accompanied the deposition of AIgG. In COVF-treated EC-rats, AIgG together with C1q was also associated with EC but no detectable C3 was seen. These data suggest clearance of AIgG via Fc and C receptors present on EC in vivo. PMID- 8436179 TI - Protective immunity induced in rat schistosomiasis by a single dose of the Sm28GST recombinant antigen: effector mechanisms involving IgE and IgA antibodies. AB - Rats immunized by a single dose of the recombinant Sm28GST antigen, using either aluminium hydroxide or Bacillus Calmette-Guerin adjuvant, were significantly protected (up to 59% reduction in worm burden) against a challenge infection with Schistosoma mansoni cercariae. A follow-up study of the humoral response revealed the presence of high levels of IgE and IgA antibodies together with specific IgG. Sera from once Sm28GST-immunized rats induced a cytotoxic response for schistosomula targets in the presence of normal rat eosinophils, similar to the one induced by sera from twice immunized rats. Depletion or competition studies indicated the participation of both IgE and IgA antibodies in eosinophil dependent cytotoxicity mechanisms. These results suggest the existence, in immunized rats exhibiting protection against schistosomiasis, of an original effector mechanism implying eosinophils and IgA antibodies, together with documented effector mechanisms involving IgE and eosinophils. In addition, they raise questions concerning the role of IgA antibodies in schistosomiasis. PMID- 8436180 TI - Covalent binding of guanine nucleotides to the CD3-gamma chain of the T cell receptor/CD3 complex. AB - In a search for proteins involved in signal transduction through the T cell receptor (TcR/CD3 complex), a recently developed highly efficient method for labeling of nucleotide binding proteins in permeabilized cells was applied. Here, we report that human CD3-gamma could be labeled by periodate-oxidized [alpha-32P] GTP (GTPoxi). In contrast to GTPoxi labeling of CD3-zeta (Peter, M. E., Hall, C., Ruhlmann, A., Sancho, J. and Terhorst, C., EMBO J. 1992. 11:933), GTP-specific labeling of CD3-gamma reached a maximum when nucleotides were added 60 min prior to the cross-linking reaction. As CD3-gamma did not contain a known consensus sequence for nucleotide binding and since labeling kinetics of CD3-gamma coincided with those of cytosolic GTP-binding proteins, labeling may have been caused by a GTP-binding protein. This putative protein was not T cell specific because labeling of CD3-gamma could also be achieved when expressed in the endoplasmic reticulum of Chinese hamster ovary (CHO) cells. In CHO cells, labeling by GTPoxi took place only when CD3-gamma was associated with CD3 epsilon, whereas labeling could not be established upon association of CD3-gamma with CD3-delta or TcR alpha. The observation that CD3-gamma was labeled without leaving the endoplasmic reticulum led to the hypothesis that the association of CD3-gamma with a GTP-binding protein might be involved in an early step of the TcR/CD3 complex formation or transport. PMID- 8436181 TI - The soluble interleukin-6 receptor is generated by shedding. AB - The ligand-binding subunit (gp80) of the human interleukin-6 receptor (IL-6R) was transiently expressed in COS-7 cells. The metabolically labeled protein was shown to be quantitatively released from the membrane within 20 h. We identified the protein released from the transfected COS-7 cells after purification to homogeneity and N-terminal sequencing as a soluble form of the gp80/IL-6R. Shedding of the gp80 protein was strongly induced by 4 beta-phorbol-12-myristate 13-acetate, indicating that the process was regulated by protein kinase C (PKC). This was further corroborated by the finding that co-transfection of a PKC expression plasmid led to enhanced shedding of the gp80 protein. Since shedding of gp80 could not be prevented by treatment of the cells with inhibitors of all known classes of proteases, a novel protease seems to be involved. As a control, an unrelated membrane protein (vesicular stomatitis virus glycoprotein) was transfected into COS-7 cells and analyzed for shedding. Since the turnover of this protein was not mediated by shedding, we conclude that the release of gp80 from COS-7 cells is a specific process. The shed gp80 protein specifically binds IL-6, and this complex shows biological activity on human hepatoma cells. Human peripheral blood monocytes released a soluble form of the gp80 protein into the culture medium upon PMA treatment indicating that PKC-regulated shedding is the physiological mechanism of generation of the soluble IL-6R. PMID- 8436182 TI - Characterization of T cell receptor assembly and expression in a Ti gamma delta positive cell line. AB - T cell antigen receptor (TcR) heterodimers of both the Ti-alpha beta and Ti-gamma delta types are expressed at the surface of T cells noncovalently associated with the CD3 complex composed of the monomorphic chains gamma, delta, epsilon and zeta. The structural relationship and assembly of the various components of this multimeric protein complex is still not fully understood. In this report, the human leukemic T cell line Lyon which expresses a Ti-gamma delta/CD3 complex, was characterized and compared to another human leukemic T cell line Jurkat (Ti-alpha beta/CD3). Membrane TCR-/CD3- variants of the T cell Lyon were induced and found to produce all of the Ti/CD3 components, with the exception of Ti-delta. Biochemical analysis indicated that: (1) Ti-gamma/CD3 gamma, delta, epsilon complexes were formed in the endoplasmic reticulum in the absence of Ti-delta; (2) the CD3-zeta chain did not associate with the Ti-gamma/CD3 gamma delta epsilon complex and (3) the Ti-delta chain was required for cell surface expression of the Ti-gamma delta/CD3 complex. Introduction of Jurkat wild-type Ti alpha cDNA into Lyon T cells resulted in Ti-alpha beta/CD3 expression and abrogated Ti-gamma delta/CD3 expression. In contrast, the expression of the Ti gamma delta/CD3 complex was not affected by transfection of a mutated Ti-alpha cDNA into Lyon cells. The mutated Ti-alpha chain formed complexes with Ti-beta and CD3 gamma delta epsilon, but the CD3-zeta chain did not associate with these complexes. Taken together analysis of Lyon cells transfected with either wild type or mutated Ti-alpha suggested that the CD3-zeta chain may have higher affinity for Ti-alpha beta/CD3 complexes than for Ti-gamma delta/CD3 complexes. PMID- 8436183 TI - T cell receptor heterogeneity in gamma delta T cell clones from intestinal biopsies of patients with celiac disease. AB - In celiac disease large numbers of gamma delta T lymphocytes infiltrate the intestinal epithelia. We have isolated intestinal gamma delta T cell clones from patients with celiac disease and have analyzed their T cell receptor repertoire. T cell lines and clones were obtained from jejunal biopsies of 14 celiac patients and 12 individuals without celiac disease. These were analyzed by staining with monoclonal antibodies against CD3, alpha beta and gamma delta T cell receptor, by Southern blot with gamma- and delta-specific probes and by polymerase chain reaction using V delta-specific oligonucleotides. Intestinal gamma delta cells from patients with celiac disease differed from those of controls with normal jejunal histology in that V delta 1+ cells and V delta 1-V delta 2- cells were significantly increased. There was no evidence of the expansion of one or more clones expressing particular types of gamma delta T cell receptor. PMID- 8436184 TI - Available lambda B cell repertoire in the mouse: evidence of positive selection by environmental factors. AB - We have recently shown that, from two BALB/c mice treated with rabbit anti-C lambda 2/C lambda 3 antibodies coupled to lipopolysaccharide, variable heavy chain (VH) family repertoires associated with lambda 2 or lambda 3 light chains can differ from one lambda subtype to another and from one individual mouse to another. Indeed, 4 out of 6 lambda 2 (VxJ2) hybridomas from one mouse preferentially expressed the VH10 family while 3 out of 8 lambda 2 (V2J2) and 5 out of 8 lambda 2 (VxJ2) hybridomas from a second mouse preferentially expressed the S107 and VGAM3.8 VH families, respectively. In this report, we describe the structural basis of such preferential pairings by sequence analysis of the 12 lambda 2 hybridomas. The sequence comparison of their VH regions show that each preferential association of a VH family to one V lambda region is restricted to the use of a single member or very closely related members inside a VH family and that a great variability of CDR3 of heavy chain is observed. We, therefore, suggest that environmental factors can modify the available lambda B cell repertoire through a positive selection of particular VH/V lambda pairings. Moreover, our data support that this selection does not require clonal expansion and punctual somatic mutation. PMID- 8436185 TI - Interferon-gamma arrests proliferation and causes apoptosis in stromal cell/interleukin-7-dependent normal murine pre-B cell lines and clones in vitro, but does not induce differentiation to surface immunoglobulin-positive B cells. AB - Normal pre-B cells from fetal liver or bone marrow of the mouse proliferate for long periods of time in tissue culture on stromal cells in the presence of interleukin-7 (IL-7). Their IgH loci are partly in germ-line, partly in DHJH rearranged configuration, while their light chain loci are in germ-line configuration. They express the pre-B cell-specific genes VpreB and lambda 5. Proliferation of these pre-B cells is inhibited by interferon (IFN)-gamma, with half-maximal inhibition at concentrations between 0.1 and 1 unit/ml. Normal pre-B cells exposed to IFN-gamma die by apoptosis, as is evidenced by the disintegration of pre-B cell DNA into oligonucleosomal multimers of 180-200 bp. While the proliferation of pre-B cells from E mu-bcl-2 transgenic (tg) mice is inhibited by IFN-gamma, these cells do not die by apoptosis. IFN-gamma does not induce differentiation to more mature B lineage cells. In the absence of IL-7 normal pre-B cells differentiate to VHDHJH/VLJL-rearranged, surface immunoglobulin-positive B cells expressing the alpha chain of the IL-2 receptor. They also down-regulate the expression of VpreB and lambda 5, and lose the capacity to proliferate on stromal cells in the presence of IL-7. In contrast, both normal and E mu-bcl-2 tg pre-B cells exposed to IFN-gamma in the presence of stromal cells and IL-7 fail to differentiate, i.e. do not express surface immunoglobulin, retain expression of VpreB and lambda 5, do not express the alpha chain of the IL-2 receptor, and retain the capacity to proliferate on stromal cells in the presence of IL-7, once IFN-gamma is removed. The potential usefulness of a treatment of acute lymphocytic leukemia of the B cell lineage (pre B-ALL) with IFN-gamma is discussed. PMID- 8436186 TI - Involvement of beta 1 integrins in the binding and entry of Trypanosoma cruzi into human macrophages. AB - We have investigated the role of integrin molecules in the binding and entry of Trypanosoma cruzi into human macrophages, with the help of monoclonal antibodies (mAb). Addition of Lia 1/2 mAb and in lesser extent of Lia 1/5 mAb, which are both specific for the beta 1 subunit of the VLA integrin family, to human macrophages blocked T. cruzi uptake and subsequent replication inside the macrophages. This inhibition correlated with their respective ability to block Fibronectin (Fn) binding to macrophages. Furthermore, another anti-beta 1 mAb, Alex 1/4, which binds to a different epitope on the beta 1 molecule and was unable to block Fn binding, did not affect T. cruzi invasion. The inhibition by Lia 1/2 and Lia 1/5 was dose dependent and clearly observable with doses as low as 1 microgram/ml. Moreover, this inhibition was T. cruzi specific since the Lia 1/2 and Lia 1/5 were unable to block uptake of Leishmania pifanoi or Escherichia coli by human macrophages. In contrast, the TS 1/18 mAb, which blocks ligand binding to beta 2 integrin, inhibited entry of L. pifanoi but not of T. cruzi. Finally, mAb specific for the alpha 4 and alpha 5 subunits of the two major Fn binding molecules of macrophages (VLA-4 and VLA-5, respectively), either alone or in combination, were poor inhibitors of T. cruzi uptake, suggesting that several members of the VLA family, including VLA-4 and VLA-5, are involved in binding and entry of T. cruzi into macrophages. PMID- 8436187 TI - Human peripheral blood gamma delta T cells are uniformly sensitive to destruction by the lysosomotropic agents leucine methyl ester and leucyl leucine methyl ester. AB - Treatment of peripheral blood mononuclear cells (PBMC) with the lysosomotropic agent leucine methyl ester (Leu-OMe) eliminates monocytes/macrophages and cytotoxic lymphocytes including CD3- CD16+ natural killer (NK) cells and a fraction of T cell receptor (TcR) alpha beta + CD8+ T cells. We report that freshly isolated peripheral blood gamma delta T cells are highly sensitive to Leu OMe treatment as well. After incubation of PBMC with 5 mM Leu-OMe or incubation of purified T cells with 50 microM leucyl leucine methyl ester (Leu-Leu-OMe) and subsequent overnight culture, CD3-CD16+ NK cells and gamma delta T cells were no longer detectable by immunofluorescence analysis. The two major gamma delta T cell subsets V gamma 9+V delta 2+ and V gamma 9-V delta 1+ were equally susceptible to Leu-OMe and Leu-Leu-OMe treatment. The elimination of V gamma 9+ T cells by Leu-OMe treatment was confirmed in functional assays. Stimulation of peripheral blood T cells with killed mycobacteria resulted in selective expansion of V gamma 9+ T cells. In contrast, no activation of gamma delta T cells was elicited in Leu-OMe-treated responder T cells stimulated with killed mycobacteria. PMID- 8436188 TI - Interleukin-4 transgenic mice of resistant background are susceptible to Leishmania major infection. AB - The outcome of cutaneous leishmaniasis is dependent on the balance of Th1 and Th2 cells. In the murine model, Th1 cells are host-protective whereas the Th2 cells are disease-promoting. However, the in vivo role of interleukin-4 (IL-4), a signature product of Th2 cells, is uncertain. We compared the course of Leishmania major infection in the genetically resistant 129/Sv mice and the mutant 129/Sv mice transgenic for the murine IL-4 gene under the control of the immunoglobulin heavy chain enhancer and promoter. We report here that in contrast to their wild-type parents, the IL-4 transgenic mice are susceptible to L. major infection. This is associated with the development of inexorably progressive lesions and parasite loads. Spleen cells from infected transgenic mice produced significantly higher levels of IL-4 but lower amounts of interferon-gamma when stimulated in vitro with leishmanial antigens compared to those from infected normal 129/Sv mice. Furthermore, sera from the infected transgenic mice contained higher levels of IL-4 and IgE than the sera of infected normal 129/Sv mice. These results, therefore, establish in a new animal model that IL-4 promotes disease development in murine cutaneous leishmaniasis. PMID- 8436189 TI - Expression of interleukin-1 receptor antagonist (IL-1ra) by human circulating polymorphonuclear cells. AB - After appropriate stimulation, mononuclear phagocytes express a specific inhibitor of interleukin (IL)-1, now re-named IL-1 receptor antagonist (IL-1ra). In this study we have examined the production of IL-1ra by polymorphonuclear cells (PMN). Human PMN isolated from peripheral blood expressed low but detectable levels of IL-1ra transcripts, which were considerably augmented after treatment with lipopolysaccharides (LPS) and cytokines [IL-4, granulocyte (G)- and granulocyte macrophage (GM)-Colony Stimulating factor (CSF), and tumor necrosis factor (TNF)]. The levels of induced IL-1 ra transcripts were comparable to those observed in endotoxin-stimulated human monocytes. By contrast IL-1 beta, interferon (IFN)-gamma and chemotactic factors (fMLP, C5a and IL-8) failed to promote IL-1ra expression in PMN. IL-1ra induction by LPS reached peak levels at 10 ng/ml after 3-6 h and remained sustained 24 h after stimulation. Induction by LPS and GM-CSF appears to be at the transcriptional level, as assessed by inhibiting mRNA synthesis with actinomycin D. Inhibition of protein synthesis by cycloheximide superinduced both basal and inducible IL-1ra mRNA. In addition to expressing mRNA, PMN also produce IL-1ra protein. Secretion of IL-1ra was induced in PMN treated with LPS, IL-4 and GM-CSF, but not by IL-1 beta, IFN-gamma and fMLP, thus yielding results that paralleled those seen in Northern blot experiments. These data indicate that, among myelomonocytic cells, PMN, in addition to mononuclear phagocytes, can express IL-1ra, suggesting that PMN, while exerting a series of pro-inflammatory activities, may also modulate the inflammatory potential of IL-1 in tissues. PMID- 8436190 TI - Cross-linking of surface IgM, but not surface IgD receptors, by soluble monoclonal antibodies primes murine B cells to secrete immunoglobulin in response to lymphokines. AB - We have previously reported the development of a two-step culture system in which soluble anti-mu monoclonal antibodies prime small resting murine B cells to secrete immunoglobulin (Ig) in response to restimulation with a mixture of interleukin-4 (IL-4) and IL-5. Here we have extended these studies to investigate the effects of engaging surface IgD (sIgD). We find that, unlike anti-mu, three different anti-delta monoclonal antibodies did not prime B cells to secrete Ig. In addition, these anti-delta antibodies inhibited anti-mu-stimulated priming for Ig secretion, while enhancing DNA synthesis in response to anti-mu. Furthermore, anti-delta antibodies still inhibited anti-mu-induced priming when added 24-48 h after anti-mu. These results therefore suggest that triggering of sIgD on B cells induces a dominant inhibitory signal which is not necessarily dependent upon co ligation of sIgM and sIgD receptors. In addition, these findings raise the possibility that ligating sIgM or sIgD receptors on mature B cells in the absence of T cell help, may produce different downstream effects. PMID- 8436191 TI - The T cell receptor alpha beta V-J shuffling shows lack of autonomy between the combining site and the constant domain of the receptor chains. AB - In order to assess the structural independence of the T cell receptor (TCR) combining site from the rest of the molecule we have generated two recombinant chains consisting of a TCR V-J alpha region linked to the C beta and a TCR V-J beta linked to the C alpha. If the V and C domains of the TCR form independent domains, as has been shown for the Ig molecules, we would expect to obtain a functional chimeric TCR. Interestingly, it was found that the shuffled molecules are produced intracellularly in T cell hybridomas, but are not expressed on the cell surface. To explain this failure of the shuffled molecules we propose that the TCR has a more compact structure, compared to the Ig, and that it is indispensable to keep a longitudinal inter-domain contact between the V-J and C portion to have a functional molecule. PMID- 8436192 TI - Impaction of maxillary canines and congenitally missing third molars. Description of an ancient skull (7250-6700 BC). AB - This report describes an ancient skull, in which both maxillary canines were impacted and mandibular third molars were missing. During the excavations at the early village site of Cayonu (Turkey), the subject of this report was found inside a skull building (charnel house) together with the fragments of 75 skulls, and was the least damaged skull of the Cayonu series (Ozbek, 1988). The skull showed skeletal and dental Class I relationship, with an orthognathic profile and a reduced bimaxillary alveolar prognathism. Assessment on the skull confirms the findings of the previous studies and reports that irregularities in the position of the teeth are already found in prehistoric man, and therefore, do not seem to be the result of modified conditions of modern civilization only. PMID- 8436193 TI - Concern for dental appearance among young adults in a region with non-specialist orthodontic treatment. AB - With limited orthodontic manpower in an area, treatment resources may be allocated to deal with a restricted number of patients, e.g. those with the most severe malocclusions, or to treat a greater number of patients by letting the specialist supervised treatment delivered by non-specialists. The purpose of the present study was to examine orthodontic concern among young adults in a region where orthodontic treatment was mainly delivered by non-specialists. The material comprised 100 individuals born in 1971 and 1972 (mean age 18.0 years) who were consecutively examined and interviewed during their annual routine dental visits. Forty subjects (19 females, 21 males) had previous orthodontic treatment. In all but four individuals treatment was delivered by general dental practitioners. Impressions for dental study casts and standardized photographs (Polaroids) were taken. The individual's occlusion was classified according to two methods: the Need for Orthodontic Treatment Index (NOTI) and Anterior Occlusal Traits (AOT). Interviews concerning the subjects' perception of their occlusion were performed with the use of questionnaires. From the answers a composite measure representing orthodontic concern was constructed. Awareness of their own dental arrangement was assessed by comparing the respondents' reports with occlusal recordings from the study casts, and by a photo-identification test. Frequencies of NOTI and AOT scores demonstrated that more than 50 per cent of the treated individuals were still assessed to be in need of treatment and exhibited deviations in the anterior region. Furthermore, 30 per cent of the treated subjects expressed concern about their occlusal appearance, and dissatisfaction was generally based on a realistic perception of their own dental appearance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8436194 TI - A comparison of the reliability and validity of the PAR Index and Summers' Occlusal Index. AB - The PAR index and Summers' Occlusal Index have both been used to assess orthodontic treatment standards. The validity and reliability of these two indices is compared when applied to a group of 80 study models. The more recently developed PAR index was found to be as reliable and as valid as Summers' Occlusal Index. PMID- 8436195 TI - A T.E.M. stereological analysis of blood vessels and nerves in marmoset periodontal ligament following endodontics and magnetic incisor extrusion. AB - Maxillary incisor fracture is a common dental injury. It is frequently treated by endodontic therapy, orthodontic extrusion, and a retention period. The aim of the study was to mimic this regime and stereologically quantify the vascular and neural reconstitution of the periodontal ligament (PDL). Ten marmosets (Callithrix jacchus) had the right maxillary incisor crown removed, root canal treatment, and magnetic incisor root extrusion of 1.2 mm. After incisor retention for 9 weeks, the animals were perfusion fixed for electron microscopy. The incisor PDL was sectioned at 250 micron intervals from the cervical to apical region and recorded for stereological evaluation. Further evaluations were conducted with a two-way analysis of covariance using program 3V of the BMDP-81 statistical software package. The total luminal PDL vascular volume was statistically unchanged. An increased occurred in the mean number of venous capillaries from 0.07 +/- 0.3 to 0.17 +/- 0.3 per 560 microns 2 of PDL (P < 0.05). Vessel wall and luminal volume of post-capillary-sized venules decreased from 1.64 to 1.03 per cent, and 5.32 to 3.04 per cent (P < 0.05), respectively. Mean luminal and abluminal diameters for post-capillary-sized venules were reduced (P < 0.05). Myelinated and unmyelinated axons showed no significant change in volume (Vv), length (Lv), or surface (Sv) densities. Axon number/unit, PDL area, and mean diameters demonstrated no statistical differences. Since the PDL demonstrated almost complete morphological re-establishment of the microvascular and axon systems, it is considered that this clinical treatment is a justifiable rationale. PMID- 8436196 TI - Class III malocclusion: the post-retention findings following a non-extraction treatment approach. AB - A retrospective, cephalometric study was made of a group of 28 successfully treated, Class III, Skeletal III children, who were considered suitable for orthodontic correction of their malocclusions. All had undergone non-extraction therapy, involving a combination of upper incisor proclination and headgear to an intact mandibular dentition and were available for review at least 2 years after all treatment and retention had ceased. Only girls over the age of 16 years and boys above 18 years of age at the post-retention recall were included. Data were examined at the beginning and end of active treatment, and at least two years out of retention. Where differences between the sexes were apparent, data for each sex were given separately. Where no significant differences were seen, data were pooled. Overjet correction was achieved by a combination of upper and lower incisor movement with no alteration in overbite. This was accompanied by a downward and backward repositioning of the mandible, redirecting, rather than restricting mandibular growth. Post-retention, demonstrable skeletal development occurred in both male and female faces. Normal patterns of facial growth reasserted themselves, reversing many treatment effects. The mandible reverted to a more horizontal direction of development, but because no growth restriction had occurred during treatment, no 'catch-up' growth of the lower jaw could be shown. Mandibular growth exceeded that of the maxilla, and since upper and lower incisor inclinations remained unaltered, both overbite and overjet reduced. Reflecting the underlying growth pattern, the lips became more retrusive. PMID- 8436197 TI - Functional and morphological-occlusal aspects in children treated for unilateral posterior cross-bite. AB - Morphological and functional aspects were investigated in children with unilateral posterior cross-bite (UPXB) before and after treatment. Sixty-five patients with Class I malocclusion with UPXB in the mixed dentition stage (mean age 8.8 +/- 1.6 years) served as the experimental group and 10 children of comparable age, with normocclusion or very mild Class I malocclusion (without UPXB) served as controls. The morphological aspects were examined on a longitudinal basis while the functional recordings, by means of a sirognathograph, were performed in a cross-sectional fashion. Complete elimination of cross-bite was maintained in 61 per cent and was accompanied by a dramatic reduction in the prevalence of functional mandibular displacement. However, the prevalence of mandibular midline deviation related to the maxillary midline as recorded in the intercuspal position was not affected. In addition, the high prevalence of Class II subdivision relationships which accompanied the UPXB in the intercuspal position was resolved in 50 per cent of the cases only. The sirognathographic recordings of the masticatory pattern showed a very high prevalence of a 'reverse sequencing' type pattern before treatment which was significantly lower following the elimination of UPXB, but still notably higher when compared with the controls. Reasons for these results are suggested and possible inter-relationships between the morphological and functional aspects are discussed. PMID- 8436198 TI - Emergence of the deciduous canines and molars in CLP children. AB - The emergence of the deciduous canines and molars was investigated as part of a longitudinal study into the emergence of the deciduous dentition in Dutch cleft lip and/or palate children (CLP) (Kramer et al., 1989). The study comprised a group of 71 CLP children and 74 normal children that served as a control. Mean emergence ages of the deciduous upper and lower canines and molars were studied. Emergence of the deciduous primary molar on the cleft side was delayed 2 months in the upper jaw and 1 month in the lower jaw in children with an unilateral cleft lip and palate. The deciduous primary molar on the non-cleft side was not delayed as compared with normal children. Local anatomical relationships could be a possible explanation for these findings. The deciduous canines and secondary molars in both jaws showed no significant differences in mean emergence ages as compared with the control group, nor between the different cleft types. No sex differences were found in any of the groups. A table is presented containing the mean emergence ages of all the teeth of the deciduous dentition for the various CLP-groups, divided in cleft and non-cleft side, and the control group. PMID- 8436199 TI - Orthodontic treatment standards in Norway. AB - The outcome of orthodontic treatment is reported for a sample of 220 patients treated by Norwegian specialist orthodontists. The outcome was assessed using objective measures. The indices can be used to identify differences not only between individual practitioners, but also health care systems. It can be confirmed that the Norwegian orthodontists are producing a high standard of orthodontic treatment, the malocclusion is on average reduced by 78 per cent. PMID- 8436200 TI - An analysis of orthodontic force systems applied to the dentition with diminished alveolar support. AB - Many more adults are undergoing orthodontic therapy than in the past. Since adult dentitions often exhibit diminished alveolar support, it is important to recognize the related apical migration of the dental centre of resistance when applying force systems to the teeth. The force system compensations necessary to produce controlled movement in this circumstance are analysed in a model of a maxillary canine undergoing translation. PMID- 8436201 TI - Inter- and intra-observer identification of landmarks used in the Delaire analysis. AB - The investigation of intra- and inter-observer tracing error of points S, N, ANS, A, B, Me, Go, and Ba (conventional cephalometric points) and some of the landmarks used in the Delaire analysis (FM, M, CT, Clp, and Br) shows that a high level of intra-observer repeatability was achieved for each landmark, and that no statistically significant differences occurred. Also there were no statistically significant differences on inter-observer comparison of averaged values for the replicate tracings of each observer. However, the gross error which may occur in an individual case may be of considerable clinical significance. PMID- 8436202 TI - Contributions made by the studies of cells in vitro for understanding of the mechanisms of aging. PMID- 8436203 TI - Metallothionein expression and stress responses in aging human diploid fibroblasts. AB - Metallothioneins (MTs) are low molecular weight proteins with a high cysteine content that are inducible by heavy metals and by other conditions of environmental stress. This laboratory was investigated in human diploid fibroblasts the induction of MTs by cadmium and by dexamethasone, and the induction of heat shock proteins, as models for age-related changes in gene expression that reflect the ability of old cells to respond to environmental stress. Old cells were more sensitive to the toxic effects of CdCl2 in the concentration range 100-175 microM. Analysis of 35S-cysteine-labelled cell extracts by polyacrylamide gel electrophoresis and fluorography showed that in the absence of any inducer, old cells have a 3.7-fold increase over young cells in the basal level of MT. The rate and extent of induction of MT by CdCl2 was reduced in old cells: Exposure of old cells to 100 microM CdCl2 for 18 h resulted in MT levels about 33% of the amount in young cells. Northern blot analysis showed that the changes in MT protein levels occurred in parallel with changes in mRNA levels, which implicates transcriptional control as the origin of these aging changes. These young/old differences in MT synthesis were maintained in density-arrested cultures, indicating that the aging changes were not due to differences in the cell cycle status of these cell populations. The rate and extent of induction of a 68-kDa heat shock protein were also reduced in old cells, which showed an increase in basal, uninduced level of this protein similar to MT. In contrast, old cells retained the ability to synthesize MTs in response to dexamethasone at a rate similar to that in young cells. PMID- 8436205 TI - Stimulation of cell proliferation by hyaluronidase during in vitro aging of human skin fibroblasts. AB - The effect of the degradation of extracellular hyaluronan on the proliferation of human skin fibroblasts in serial cultures during in vitro aging was investigated. Human skin fibroblasts at different time intervals from 3rd to 36th passages were exposed after plating to bovine testicular hyaluronidase. The enzyme treatment resulted in an increase in cell proliferation (cell number vs. time) as compared to the untreated control fibroblasts. The effect was dose dependent, reversible, and was independent of the type of the glycosidic linkage cleaved in hyaluronan. The increased proliferation was observed at all passages when untreated cells underwent mitosis. The degradation of hyaluronan induced cell proliferation up to the presenescent phase. Depletion of hyaluronan did not induce proliferation of postmitotic fibroblasts. The incorporation of 3H-glucosamine into hyaluronan decreased with increasing cell passages (increase of the number of population doublings). Twenty-fourth passage fibroblasts accumulated about two time less hyaluronan in the medium than ninth passage cultures. Following hyaluronidase treatment, the amount of newly synthesized, labeled hyaluronan increased in the medium. Accordingly, the fibroblasts restored the degraded hyaluronan even in the declining phase of proliferation (phase III according to Hayflick). PMID- 8436204 TI - Growth properties of familial Alzheimer skin fibroblasts during in vitro aging. AB - Human diploid fibroblasts undergo replicative senescence in vitro, which is strongly correlated with biological aging in vivo. In order to examine whether features compatible with a systemic premature aging are present in familial Alzheimer's disease (FAD) patients, we investigated the growth characteristics of three skin fibroblast lines from FAD patients and from three sex/age-matched controls at different passages until senescence was reached. A kinetic study of the replicative capacity was performed at different culture times by [3H] thymidine incorporation and crystal violet staining. Data showed no significant difference between the two groups at any studied passage. The life span of the two types of cultures was also comparable. These results suggest that in familial Alzheimer patients there are not systemic signs of accelerated aging. PMID- 8436206 TI - Age-related changes in the position of centrosomes in endothelial cells of the rabbit aorta. AB - The position of centrosomes in endothelial cells (EC) lining the aorta was examined in rabbits at different ages, using en face preparations and immunofluorescent staining with a serum that specifically labels centrioles. The results obtained show that in young rabbits (4 h-6 weeks) the great majority of the EC (61%) had centrosomes on the heart side of the nucleus, whereas in older rabbits (6-156 weeks) only 41% of the EC had centrosomes oriented toward the heart. The results suggest that the orientation of structures normally associated with centrosomes such as the microtubule organizing centers and the Golgi apparatus also change with age. The change in the orientation of centrosomes and associated structures along the longitudinal axis of the cell with age could affect the function and behaviour of EC and their ability to respond to injury. PMID- 8436207 TI - Influences of chronic tobacco smoke inhalation on aging and oxidant-antioxidant balance in the senescence-accelerated mouse (SAM)-P/2. AB - We studied the influences of chronic tobacco exposure on aging and oxidant antioxidant balance in two different strains of mice, hitherto called SAM (senescence-accelerated mice). One is a senescence-prone strain, "SAM-P/2," and another is a senescence-resistant strain, "SAM-R/1." We used 100 male mice--20 young (12 weeks of age) mice and 30 mature (24 weeks of age) mice from each strain. Half of each series were housed in a Hamburg II machine and exposed to tobacco smoke inhalation for five weeks. The result was that fewer of the mature SAM-P/2 survived compared with the mature SAM-R/1 after chronic tobacco inhalation. The grading of senility in the mature SAM-P/2 was also significantly higher than that in the mature SAM-R/1. The reduction of glutathione contents of blood and liver after tobacco exposure in the mature SAM-P/2 was greater than that in the young SAM-P/2 and the mature SAM-R/1. Moreover, oxygen radical generation of total blood cells stimulated by phorbol-myristate-acetate or opsonized zymosan showed a greater increase in the mature SAM-P/2 compared to the young SAM-P/2 and the mature SAM-R/1. These results indicate that the senescence prone strain (SAM-P/2) was more susceptible to tobacco smoke exposure than the resistant strain (SAM-R/1). The impaired oxidant-antioxidant balance in the SAM P/2 may therefore contribute to the process of senescence acceleration. PMID- 8436208 TI - First International Symposium on Neurobiology and Neuroendocrinology of Aging, July 19-24, 1992, Bregenz, Austria. PMID- 8436209 TI - Synovial-type (group II) phospholipase A2 in serum of febrile patients with haematological malignancy. AB - Elevated concentrations of synovial-type (group II) phospholipase A2 (PLA2-II) in serum are associated with septic bacterial infections. We measured the concentrations of PLA2-II in serum in 24 fever episodes involving patients suffering from haematological malignancies and having fever after cytotoxic treatment. We applied a novel time-resolved fluoroimmunoassay using a polyclonal antibody raised against recombinant human synovial-type PLA2. The concentrations of PLA2-II in serum were 194.7 +/- 204.4 micrograms/l (mean +/- SD, median 141.9, range 4.6-931.5 micrograms/l). The concentrations of PLA2-II correlated well to the concentrations of C-reactive protein (CRP) in serum (r = 0.688, p < 0.001). The PLA2-II concentrations increased faster than the corresponding CRP values and began to decrease 12 hours after the beginning of antimicrobial treatment. Inverse correlations were found between the concentrations of PLA2-II and blood neutrophil and platelet counts. No correlation was found between the concentrations of PLA2-II and the duration of the time interval from the onset of preceding cytotoxic and corticosteroid treatment to the first blood sample. The concentration of pancreatic PLA2 was within the reference interval in all samples. The present results indicate that PLA2-II resembles an acute-phase protein and is not of blood cell or pancreatic origin. PMID- 8436210 TI - On the interaction between cytosine arabinoside and etoposide in vivo and in vitro. AB - Cytosine arabinoside (ara-C) and etoposide are often used in combination in the treatment of acute myelocytic leukemia (AML). The intracellular phosphorylation of ara-C to its 5'-triphosphate (ara-CTP) is a prerequisite for its cytotoxic effects. It has been shown in vitro that etoposide can impair the formation of ara-CTP in leukemia cells. The present study was undertaken in order to elucidate whether this interaction may be of clinical importance. Leukemia cells were isolated from 3 patients with acute myelocytic leukemia and incubated in medium (RPMI-1640) with or without 10% fetal calf serum or in human plasma. When the cells were incubated in RPMI-1640 with ara-C (10 mumol/l) and etoposide during 2 h, the formation of ara-CTP was decreased to 71 +/- 18 (mean +/- S.D.) and 30 +/- 15% of control at 1 and 10 micrograms/ml etoposide, respectively. When the cells were incubated in human plasma, the formation of ara-CTP was not influenced by the presence of etoposide (101 +/- 6 and 103 +/- 20% at 1 and 10 micrograms/ml etoposide). When incubated in RPMI supplemented with 10% fetal calf serum, the corresponding figures were 81 +/- 8 and 70 +/- 20%. Six patients with AML were therefore treated with ara-C 0.5 or 1.0 g/m2 as a 2-h infusion every 12 h and, during 1 h before the second ara-C infusion, 100 or 200 mg/m2 etoposide was administered. The median change in the AUC of cellular ara-CTP between the first and second ara-C dose was 0% (-37 to +21%). The corresponding median change in rate of accumulation of ara-CTP in leukemia cells was 12% (-26 to +110%). The concentration of etoposide in plasma during the ara-C infusion was 18.7 +/- 5.1 micrograms/ml while the non-protein bound etoposide was 0.73 +/- 0.34 micrograms/ml. Thus, despite exposure to higher etoposide concentrations in vivo than in vitro, no impairment of ara-CTP formation was seen in the patients. This corresponds to the results obtained when leukemic cells were incubated in plasma. It is concluded that the inhibition of ara-CTP formation by etoposide seen in vitro is offset by the high protein binding of etoposide in plasma (96%) and that etoposide does not impair the formation of ara-CTP in leukemia cells in vivo during treatment with standard-dose etoposide. PMID- 8436211 TI - Red cell destruction by human monocytes--changes in intracellular ferritin concentration and phenotype. AB - Mononuclear cells from 5 normal men and 5 patients homozygous for hereditary haemochromatosis (HFE) have been incubated for 18 h with or without the addition of sheep red blood cells coated with antibody (SRBC). In the absence of SRBC mean H type ferritin concentrations were greater than L type (normals: mean L type 11.6 ng/10(6) cells, H type 15.5; patients, L type 23.5 ng/10(6) cells, H type 41.6). In the presence of SRBC, monocyte L type ferritin concentrations increased considerably (76 ng/10(6) cells in normals and 141 ng/10(6) cells in patients) but H type ferritin concentrations were the same or decreased compared with incubation in medium only. Incubation with additional iron (ferric ammonium citrate, 2.5 micrograms Fe/ml) increased both H and L type ferritin concentrations. Erythrophagocytosis thus appears to cause differential regulation of H and L ferritin subunit synthesis or breakdown. Normal subjects and patients do not differ in this response to erythrophagocytosis. PMID- 8436212 TI - Comparative pharmacokinetics of single-dose administration of mammalian and bacterially-derived recombinant human granulocyte-macrophage colony-stimulating factor. AB - Pharmacokinetics of recombinant human non-glycosylated bacterially-synthesized (E. coli) granulocyte-macrophage colony-stimulating factor (GM-CSF) were studied following single intravenous (i.v.) and subcutaneous (s.c.) bolus injection, and compared to equivalent doses of glycosylated mammalian-derived CHO-GM-CSF. Each route of administration gave a different GM-CSF concentration-time profile. The highest peak serum concentrations (Cmax) were observed following i.v. bolus injection. After i.v. administration, a two-phase decline in concentration was noted for both types of GM-CSF with a significantly shorter t1/2 alpha of 7.8 minutes for the E. coli GM-CSF versus 20.0 min for the CHO-GM-CSF, while no significant difference was observed for the terminal phase. Following s.c. administration of equivalent doses, a higher peak serum concentration was observed in the E. coli-treated patients and, again, a faster elimination where pretreatment serum levels were reached after 16-20 h, versus more than 48 h after administration of CHO-GM-CSF. Although the non-glycosylated E. coli GM-CSF thus seems to undergo a faster elimination that the glycosylated CHO-GM-CSF no significant difference could be demonstrated in the in vivo effect of corresponding doses of the two compounds with respect to stimulation of granulopoiesis--with reservation for small patient numbers and a large individual variations in response. PMID- 8436213 TI - Lomustine, etoposide, methotrexate and prednisone (LEMP) therapy for relapsed and refractory non-Hodgkin's lymphoma. AB - Twenty-two patients with non-Hodgkin's lymphoma (NHL) were treated with a regimen aimed at administering 6-9 cycles at 6-weekly intervals of oral lomustine (CCNU) 50 mg/m2 on day 2, i.v. etoposide 50 mg/m2 d 1 and 8, methotrexate 30 mg/m2 d 1 and 8, prednisone 60 mg/m2 d 1-10 (LEMP). The patients had a median age of 65 years (range 34-81) at diagnosis and comprised 14 males and 8 females. Eighteen patients had had prior chemotherapy (5 patients received more than two combinations). Seven had also received prior radiotherapy. Five patients achieved a complete remission (CR) with a median duration of 18 months (range 4-37). Twelve patients achieved a partial remission with a median survival of 8 months (range 2-45). Responses were seen in 6/6 nodular small cleaved cell, 1/1 diffuse small cleaved cell, 0/2 nodular mixed small and large cell, 3/4 diffuse mixed small and large cell, 7/9 diffuse large cell. One patient with diffuse large cell histology was treated initially with LEMP, achieving and maintaining CR for 18 months. Five patients did not respond to LEMP. This regimen was well tolerated requiring only 2 injections every 6 wk, there was minimal toxicity, no alopecia or cardiotoxicity, and little myelosuppression. There were no treatment-related deaths. This regimen has a useful role in inducing partial or complete remission in patients who have relapsed or progressed following previous intensive chemotherapy. It may also be used as first-line therapy in patients who may not tolerate more intensive regimens. These results are encouraging and warrant further investigation. PMID- 8436214 TI - Potential of bone marrow biopsy in chronic myeloproliferative disorders (MPD). AB - The chronic myeloproliferative disorders (MPD) comprise polycythemia vera (PV), idiopathic thrombocythemia (IT), chronic myeloid leukemia (CML) and myelofibrosis/osteomyelosclerosis (MF/OMS). Bone marrow biopsies of 3500 patients with known or suspected MPD were studied, and the clinical and morphologic variables registered were utilized for multivariate data analysis by selected BMD computer programs. The histologic criteria and the histologic subdivisions, as well as the evolution and prognosis of disease are outlined for each of the clinical entities. The results show that a bone marrow biopsy provides independent diagnostic and prognostic data in this group of hematologic malignancies and therefore constitutes an additional parameter in the diagnostic investigation of patients with suspected or established MPD. PMID- 8436215 TI - Hodgkin's disease revealed by cutaneous vasculitis: two cases. PMID- 8436216 TI - Increased uptake and accumulation of cobalamin by multiple myeloma bone marrow cells as a possible cause of low serum cobalamin. PMID- 8436217 TI - Serum acid phosphatase in patients with polycythaemia vera. PMID- 8436218 TI - Functional size of the thylakoid phosphatases determined by radiation inactivation. AB - Radiation inactivation technique was employed to determine the functional size of phosphatases from thylakoid membrane. The enzymatic activities of phosphatases decayed in a simple function with the increase of radiation dosage. D37 values of 18.8 +/- 2.4-14.1 +/- 1.5 Mrad were obtained, using phosphoserine, phosphothreonine, p-nitrophenol phosphate, and phospho-histone V-S, respectively, as substrates. The molecular masses of 48.2 +/- 6.3-61 +/- 5.7 kDa were yielded by target theory analysis. We thus speculate that the thylakoid alkaline phosphatase is probably a monomer while acid phosphatase is functionally a dimer in situ. PMID- 8436219 TI - Identification of zinc-binding ligands in the class II fructose-1,6-bisphosphate aldolase of Escherichia coli. AB - An expression and mutagenesis system for the E. coli Class II fructose-1,6 bisphosphate aldolase has been created by modification of the vector pKfda (Biochem. J. 257 (1989) 529-534). Large amounts of Class II aldolase (about 1 g/l in crude extracts), with properties consistent with those previously reported for the naturally occurring enzyme (Biochem. J. 169 (1978) 633-641) are obtained. The enzyme contains 2 zinc ions per enzyme dimer. We have investigated the nature of the zinc-binding site of the enzyme by site-directed mutagenesis. His-108, His 111, Cys-112 and His-142 were identified as possible zinc-binding ligands by sequence alignments and comparisons with other known zinc-containing enzymes. Mutation of these residues identified His-108 and His-111 as two of the ligands directly responsible for the tight binding of zinc. Mutation of the other two residues results in only a small effect on the amount of zinc bound per monomer and a corresponding change in specific activity. These residues are, therefore, unlikely to be directly involved in zinc binding, but may be indirectly involved in some manner in the zinc-binding environment. PMID- 8436220 TI - Kinetic studies of the active sites functioning in the quinohemoprotein fructose dehydrogenase. AB - Steady-state kinetic analysis was performed on the reaction between D-fructose and ferricyanide with the quinohemoprotein fructose dehydrogenase from Gluconobacter species. The D-fructose oxidation dependence on the ferricyanide concentration resulted in a series of parallel reciprocal plots, and the reaction was assumed to proceed by a ping-pong type of mechanism. A reciprocal plot of the reduction of ferricyanide at saturating concentration of D-fructose gave a break which was considered to appear as a result of the two active centers, namely PQQ and heme c functioning. A scheme of action is proposed and the bimolecular rate constant of the D-fructose oxidation, the kcat for PQQ and the electron transfer rate between the PQQH2 and heme c are calculated and account for 2.2 +/- 0.4 x 10(4) M-1 s-1, (93 +/- 14) and (162 +/- 7) s-1, respectively. PMID- 8436221 TI - Glutathione in whole blood: a novel determination using double quantum coherence transfer proton NMR spectroscopy. AB - Double quantum selective coherence transfer proton NMR spectroscopy has been used to observe glutathione in whole blood. The efficient water suppression of this technique avoids the need to resuspend the cells in D2O, hence avoiding equilibrium and kinetic isotope effects. Using this method we estimate the concentration of glutathione in fresh whole rabbit blood at approximately 1.7 mM. PMID- 8436222 TI - Detection of a plant protein analogous to the yeast spliceosomal protein, PRP8. AB - We have investigated whether a spliceosomal protein analogous to the yeast protein, PRP8, was present in higher plants. A protein with a molecular weight > 200 kDa was detected in Western blots of tobacco (Nicotiana tabacum L.) nuclear extracts with affinity-purified antibodies, raised against four different beta galactosidase-PRP8 fusion proteins. The < 200 kDa protein was also immunoprecipitated by antibodies against the snRNA-specific trimethylguanosine cap structure and was, therefore, snRNP-associated. The presence of this protein in plants, in addition to yeast, Drosophila and humans, and the conservation of large size and epitopes highlights the importance of PRP8 in pre-mRNA splicing. PMID- 8436224 TI - Isolation and partial characterization of cholesterol pronucleating hydrophobic glycoproteins associated to native biliary vesicles. AB - Cholesterol is transported both in unilamellar phosphatidylcholine vesicles and in bile salts-mixed micelles in native bile. The vesicular carrier of biliary lipids apparently has a well defined protein profile with a potent cholesterol crystallization-promoting activity. This study was conducted to identify and further characterize these vesicular proteins and to test the effect of isolated vesicular proteins on the cholesterol crystal formation in supersaturated model bile. The results confirmed that proteins are a constant component of highly purified biliary vesicles both in hepatic and gallbladder bile. Immunoglobulins (IgA, IgG and IgM) and albumin are associated to the purified hepatic biliary vesicles. Furthermore, four different hydrophobic glycoproteins with a molecular mass of 130, 114, 86, and 62-67 kDa were isolated. These glycoproteins showed no reactivity with anti-human whole serum or anti-immunoglobulin antibodies, suggesting that these proteins are biliary-specific. Isolated 130, 114 and 62-67 kDa vesicular glycoproteins significantly decreased the cholesterol nucleation time in artificial model bile. We concluded that some, but not all, vesicular bound hydrophobic glycoproteins have cholesterol pronucleating activity and they may be involved in the pathogenesis of cholesterol gallstone disease. PMID- 8436223 TI - Identification of domains of a cloned rat brain GABA transporter which are not required for its functional expression. AB - The sodium and chloride coupled gamma-aminobutyric acid (GABA) transporter purified from rat brain, belongs to a superfamily of neurotransmitter transporters. They are involved in the termination of synaptic transmission and are predicted to have 12 membrane spanning alpha-helices with both amino- and carboxyl-termini oriented toward the cytoplasm. In order to define the domains not required for functional expression, we have constructed and expressed a series of deletion mutants in GAT-1, the cDNA clone encoding for the transporter. Transporters truncated at either end until just a few amino-acids distance from the beginning of helix 1 and the end of helix 12, retain their ability to catalyze sodium and chloride-dependent GABA transport. PMID- 8436225 TI - Inhibition of myosin ATPase activity by human myasthenia gravis antibodies reactive with the acetylcholine receptor. AB - Antibodies, obtained from myasthenia gravis patients, with reactivity for an immunodominant region of the nicotinic acetylcholine receptor were found to also react with muscle myosin. Since amino acid sequence analyses have previously suggested possible serological relationships between AChR and a head region sequence of myosin heavy chain, cross-reactive antibodies were examined for their ability to interfere with ATPase activities associated with this region of myosin. Results indicated that AChR-specific antibodies purified from MG patient serum by binding to and elution from antigen columns were found to inhibit Ca(2+) dependent, myosin-associated ATPase activity; interestingly, this inhibition appeared to be relatively selective in that neither K+(EDTA)-dependent nor Mg(2+) dependent ATPase activities were sensitive to antibody-mediated interference. PMID- 8436226 TI - Opposite regulations by androgenic and thyroid hormones of V1 myosin expression in the two types of rabbit striated muscle: skeletal and cardiac. AB - The finding that V1 cardiac myosin is expressed in masticatory skeletal muscles of the rabbit provided a unique opportunity for comparing the hormonal regulation of V1 in skeletal and cardiac muscles. Thyroid hormones had no significant effect on the postnatal expression of V1 in masticatory muscles, but increased this expression in cardiac ventricles. In contrast, androgenic hormones reduced V1 expression in masticatory muscles, but did not affect it significantly in cardiac ventricles. Modulation of V1 gene transcription in striated muscle is thus shown here to depend both on the target muscle and on the hormone. PMID- 8436227 TI - The temperature-dependent expression of the desaturase gene desA in Synechocystis PCC6803. AB - We examined the temperature-dependent regulation of the expression of the desA gene, which encodes delta 12 desaturase of Synechocystis PCC6803. The level of desA transcript increased 10-fold within 1 h upon a decrease in temperature from 36 degrees C to 22 degrees C. This suggests that the low-temperature-induced desaturation of membrane lipid fatty acids is regulated at the level of the expression of the desaturase genes. The accumulation of the desA transcript depended on the extent of temperature change over a certain threshold level, but not on the absolute temperature. PMID- 8436228 TI - Different sec-requirements for signal peptide cleavage and protein translocation in a model E. coli protein. AB - We describe a secretory E. coli protein with a novel phenotype: signal peptide cleavage is largely unaffected whereas chain translocation is efficiently blocked under conditions where SecA, a central component of the secretory machinery, is rendered non-functional, and we have traced this phenotype to the presence of a mildly hydrophobic segment located approximately 30 residues downstream of the signal peptide. When this segment is deleted, normal SecA-dependent signal peptide cleavage and chain translocation is observed; when its hydrophobicity is increased, it becomes a permanent membrane anchor with cleavage of the signal peptide and membrane insertion both being SecA-independent. These findings suggest that the initial insertion of the signal peptide across the membrane can be uncoupled from the translocation process proper. PMID- 8436229 TI - Lysolipids reversibly inhibit Ca(2+)-, GTP- and pH-dependent fusion of biological membranes. AB - Membrane fusion in exocytosis, intracellular trafficking, and enveloped viral infection is thought to be mediated by specialized proteins acting to merge membrane lipid bilayers. We now show that one class of naturally-occurring phospholipids, lysolipids, inhibits fusion between cell membranes, organelles, and between organelles and plasma membrane. Inhibition was reversible, did not correlate with lysis, and could be attributed to the molecular shape of lysolipids rather than to any specific chemical moiety. Fusion was arrested at a stage preceding fusion pore formation. Our results are consistent with the hypothesis that biological fusion, irrespective of trigger, involves the formation of a highly bent intermediate between membranes, the fusion stalk. PMID- 8436230 TI - The secondary structure of bacteriorhodopsin in organic solution. A Fourier transform infrared study. AB - Fourier transform infrared spectroscopy is used to estimate the secondary structure of bacteriorhodopsin dissolved in chloroform-methanol (1:1 v/v), 0.1 M LiClO4. Curve-fitting of the deconvolved spectra in the amide I region shows that the total content of alpha-helices, reverse turns and beta-sheets are similar to the native state. However, the alpha II-helices, which are the major helical class in native bacteriorhodopsin, are greatly decreased in the solubilized sample. Similarly, the reverse turns and the beta-sheets are strongly altered. PMID- 8436231 TI - Around the growth phase transition S. cerevisiae's make-up favours sustained oscillations of intracellular metabolites. AB - Under a limited set of hitherto incompletely defined conditions, inhibition of respiration has been shown to cause transient oscillations in NAD(P)H fluorescence of yeast cells. In this paper, we apply a new method [1992, Anal. Biochem. 204, 118-132] for extraction of intracellular metabolites. This method involves spraying the cells into -40 degrees C methanol; the neutral pH allows extraction of nearly all intracellular metabolites, including NADH. Close to the shift from glucose to ethanol as a growth substrate, the cells acquire a make-up amenable to sustained oscillations in intracellular concentrations of NADH and glycolytic intermediates such as glucose-6-phosphate. NADH was found to oscillate between 200 microM and 400 microM intracellular concentration. The cellular make up determining the tendency to oscillate is 'remembered' by the cells after three hours of starvation. PMID- 8436232 TI - Inhibition of protein prenylation by patulin. AB - The antibiotic patulin was found to inhibit protein prenylation in mouse FM3A cells. Thus, the agent reduced incorporation of [3H]mevalonate into proteins by 50% at a concentration of 7 microM. In a cell-free assay, patulin inhibited rat brain farnesyl:protein transferase, one of the enzymes responsible for protein prenylation. The inhibition was 50% at a concentration of 290 microM. PMID- 8436234 TI - Therapeutic possibilities and limits in multiple primary carcinomas: consideration of 38 cases. AB - The authors report their experiences of 38 cases of multiple primary carcinomas, of which 17 were synchronous and 21 metachronous. Some of them were localized to the same organs and others on different organs. It is important that diagnosis be established in due time for the first and most of all, for the second or third tumour. Surgery by tumour exeresis constitutes the main treatment, being associated with radiotherapy and chemotherapy as adjuvants. The results recorded here may be considered to be quite good, since many patients reached 5 years of survival, both after the first and after the second operation. Thus, mean survival was 5.53 years in the 17 patients with synchronous carcinomas and more than 10 years in the 21 cases of metachronous carcinomas, i.e. 8.9 years after the first operation +4.05 years after the second operation with a 2.63 mortality rate. PMID- 8436233 TI - Expression of human thromboxane synthase using a baculovirus system. AB - Human thromboxane (TX) synthase (EC 5.3.99.5) was produced by the baculovirus expression system using cDNA encoding human TX synthase [(1991) Biochem. Biophys. Res. Commun. 78, 1479-1484]. A recombinant baculovirus TXS7 was expressed in Spodoptera frugiperda Sf9 insect cells. The expressed protein was recognized by monoclonal antibody, Kon 7 raised against human TX synthase [(1990) Blood 76, 80 85]. The recombinant TX synthase catalyzed the conversion of prostaglandin (PG) H2 to TXA2 and 12-hydroxy-heptadecatrienoic acid (HHT). Both conversions of PGH2 to TXA2 and HHT by the expressed TX synthase were completely inhibited by a specific TX synthase inhibitor, OKY-046 (5 microM). PMID- 8436235 TI - Wound dressing in major head and neck cancer surgery: a prospective randomized study of gauze dressing vs sterile vaseline ointment. AB - A total of 207 patients were randomized in a prospective comparative study of standard gauze dressing vs sterile vaseline ointment. 179 patients were evaluable. All patients received antimicrobial prophylaxis. The two groups (86 standard and 93 vaseline) were comparable as far as age (mean, 57 yr; range, 21 84), genders (155 males/24 females), weight (mean, 66 kg; range, 40-69), type of surgery, previous or concomitant anticancer treatment. Severity of surgery was identical, as was the severity of cancer, in the two groups. Wound infection within 20 days of surgery occurred in 31.2% (29/93) of the vaseline group and 24.4% (21/86) in the standard group (NSS). Bacteremia occurred in three patients from the vaseline group and in four patients from the standard group. Bronchopneumonia occurred in 10 patients from the vaseline group and 14 patients in the standard group. The spectrum of microorganisms recovered was similar in the two groups. The need for antimicrobial treatment (empiric or for documented infections) within 20 days after surgery was 34.4% (32/93) in the vaseline group and 36.0% (31/86) in the standard group. The median delay to infection (range in days) in the vaseline group was 9 (5-15) for wound and 6 (1-12) for bronchopneumonia. For the standard group the corresponding delays were 8 (4-15) and 7 (2-19). Vaseline dressing was not associated with an increased risk of infection as compared to the standard gauze dressing. PMID- 8436236 TI - Management of thymoma. A retrospective study. AB - Thymoma is a relatively rare tumour. Twelve cases seen in Kuwait Cancer Control Centre over a period of 10 years were analyzed. Two patients had Myasthenia gravis at presentation, and one developed it after the treatment, during remission. Six patients had total resection and four had subtotal resection of the tumour; the remaining had only diagnostic biopsy. All the six patients who had total resection were alive, disease-free with three of them Stage III, whereas, of the four cases who had subtotal resection two are dead, one with local disease and the other with pulmonary metastases. Eight patients were given postoperative radiotherapy and none of them relapsed at the primary site. Of the three patients who had chemotherapy, two had partial remission, and the remaining one failed to show any response. Patients with predominantly epithelial type histology fared worse compared to predominantly lymphocytic type and mixed cell type. Histological subtypes, invasiveness of the tumour and completeness of resection and association of Myasthenia gravis as prognostic features are discussed. The role of radiotherapy and chemotherapy as adjunctive treatment to surgery is reviewed. PMID- 8436237 TI - Hydronephrosis in malignant tumors: rationale and efficiency of endo-urological diversions. AB - The improvement of minimal invasive endo-urological urinary diversions in patients with malignant ureteral obstruction (MUO) provides an alternative to open surgery. Endo-urologic procedures cause less morbidity than conventional surgical techniques. From April 1986 to April 1989, 52 patients suffering from MUO representing 64 reno-ureteral units were treated by endo-urological diversions. Proper drainage was achieved in all cases. Initial retrograde JJ stenting was successfully performed in 30 instances. Percutaneous nephrostomy tubes were primarily placed in 34 units. Fourteen of these were finally changed to a JJ-stent in eleven cases and an ileal conduit in three. Percutaneous ureteral occlusion was performed in 7 units. A positive response regarding the effect of endo-urological treatment on the patient's quality of life was obtained in 81%. Further therapies of the underlying diseases were performed in more than 30% after stabilized renal function. MUO can be treated in most cases with little morbidity and frequently without the use of external collecting devices. PMID- 8436238 TI - Neuroblastoma--a surgical perspective. AB - The role of an aggressive surgical policy in the management of neuroblastoma (NBL) was examined in a retrospective study from a total of 57 patients presenting to a single institution between 1979 and 1989. Surgery consisted of either primary excision of tumour or elective resection following intensive chemotherapy. Two year disease-free survival (DFS) for the entire group was 100% for Stage I patients (n = 2), 86% for Stage II (n = 7), 55% for Stage III (n = 11), 12% for stage IV (n = 33) and 50% for stage IVs (n = 4). In all long-term survivors, surgical excision of primary tumour had been achieved. Elective surgery of primary tumour was not performed in six patients with Stage IV disease; median survival for these patients was eight months compared with 19 months for those other patients with Stage IV disease who did have surgery +/- high dose melphalan and autologous bone marrow rescue. Postoperative complications were documented in 13 of 48 operated patients (27%), emphasising the technical challenges encountered in resection of NBL. Age at presentation and site of primary tumour were major factors affecting prognosis: patients who presented < 1 years of age (n = 15) achieved 80% DFS, > 1 year and < 2 years (n = 12), 33%, and > 2 years (n = 30) 13%; 10 of 11 patients (91%) with primary supradiaphragmatic disease are alive and well compared with 10 out of 46 (22%) with infradiaphragmatic disease (P = 0.01). Based on the experience from this centre, it would appear that surgery can be curative for patients with Stage I, II and III disease but can only, at best, prolong DFS for Stage IV patients. Alternative therapeutic strategies are indicated for this latter group of patients. PMID- 8436239 TI - Regional isolated perfusion with melphalan for patients with subungual melanoma. AB - From 1978 to 1990, 24 patients with subungual melanoma (MD Anderson Stage I, 17, Stage III, 7 patients) were treated with amputation of a digit and regional isolated perfusion with melphalan. The lesions were located on the big toe in 14 (58%) patients. Median delay in definitive treatment was 21 months, while 14 patients (58%) had been subjected to some form of inadequate treatment before correct diagnosis was made. Median follow-up for the living patients was 48 months. Overall 5-year survival was 54% (Stage I, 68%, Stage III, 19% (log-rank P = 0.003)). Sex and site of the lesion did not influence survival. Compared to literature data of patients treated by amputation alone, no improvement in survival could be demonstrated despite perfusion treatment. Moreover, two limb and 7 regional node recurrences were seen. The benefit of adjuvant perfusion in the treatment of Stage I subungual melanoma has not been demonstrated in this study. The results of prospective randomized trials in primary high-risk extremity melanoma have to be awaited. PMID- 8436240 TI - Early cancer of the gastric remnant with special reference to the importance of follow-up of gastrectomized patients. AB - Seven patients with early cancer of the gastric remnant (group 1) and nine with gastric remnant cancer that developed after surgery for early gastric cancer (group 2) were studied clinicopathologically. In group 1, the great majority of cases were classified as type I by gross type. Most lesions existed in the posterior wall of the remnant stomach. All lesions were differentiated carcinomas. In group 2, six of the nine early gastric tumors resected at the initial surgery were present in site A and three in site M. Gross tumours were of various types. Six patients underwent Billroth II resection and two underwent Billroth I resection. At second surgery (for gastric remnant cancer) four lesions were found to be located in the gastric stump or anastomosed region and five in the posterior wall of the stomach remnant. Histologically, the lesions included four undifferentiated carcinomas and five differentiated carcinomas. Of the nine lesions involving the gastric remnant, only two were early stage: the remaining seven were in an advanced stage. Prognosis was extremely poor in the group, many patients dying of carcinomatous peritonitis. In summary, most group 1 patients had a type I lesion in the remnant stomach. In group 2, more than half of the lesions were present in the gastric stump or anastomosed site and most were in an advanced stage. These observations suggest that it is very important to follow up patients operated on for early gastric cancer in order to detect malignant lesions, if any, in the remnant stomach before disease progresses to a stage at which radical resection is no longer possible. Follow-up will no doubt improve long-term results following surgery for early gastric cancer. We consider endoscopic examination and biopsy, especially of the gastric stump and anastomosed site, of great importance for gastrectomized patients. PMID- 8436241 TI - Interconnection of integrins alpha 2 and alpha 3 and structure of the basal membrane in colorectal cancer: relation to survival. AB - The expression and distribution of integrin subunits alpha 2 and alpha 3 and two of their putative ligands, type IV collagen and laminin, were examined by immunohistochemistry in specimens from 33 consecutive patients operated on for colorectal adenocarcinomas. Both tumour cells and normal epithelium expressed the alpha 2 and alpha 3 subunits. Two typical patterns of expression could be discerned; a basolateral expression and a diffuse cytoplasmic expression. The stained tumour specimens were assessed according to (i) distribution of integrin expression (diffusely cytoplasmic or basolateral), (ii) continuity in basolateral integrin expression, and (iii) interconnection of integrin expression and expression of type IV collagen and laminin. These parameters were then related to tumour differentiation, tumour stage according to Dukes' classification, DNA ploidy and patient survival (median observation time was 30 months; range 24-35). The continuity in the basolateral expression of alpha 3 but not of alpha 2, correlated with the basal membrane expression of type IV collagen (P < 0.001). Loss of continuity in the basolateral expression of both integrins was significantly related to impaired tumour differentiation (alpha 2 P = 0.02; alpha 3 P = 0.01), more advanced Dukes' stage (alpha 2 = 0.07, alpha 3 P < 0.001), survival rate (both integrins P < 0.05), but not to DNA-ploidy. These data suggest that determination of the pattern of expression of the integrin subunits alpha 2 and alpha 3 in the preoperative biopsy and the surgical specimen could be used as a prognostic indicator. PMID- 8436242 TI - The impact of resection margins in the treatment of primary sarcomas of the breast. A clinicopathological study of 8 cases with review of literature. AB - We reviewed the clinical and pathological features of eight patients (seven females, one male), who underwent surgery for sarcomas of the breast, to evaluate the effect of the margins of resection and histological tumor type on survival. Patients with carcinosarcoma, cystosarcoma phyllodes or dermatofibrosarcoma protuberans were excluded. Tumor size ranged between 4.5 and 26 cm (median 12.8 cm); there were three grade 3, four grade 2 and one grade 1 lesions. Of the five patients treated by radical resection margins, two with large grade 3 sarcomas died of distant metastasis 3 and 10 months later. One patient out of the five radical resected patients developed a local recurrence 96 months later. The recurrence was resected radically, radiotherapy was administered, and the patient is still alive at 168 months. The remaining four radical resected patients are free of disease until now. One of three patients, treated by wide or marginal resection, received adjuvant radiotherapy. This patient developed local recurrence and solitary distant metastasis at 26 and 49 months, respectively, and died of multiple distant metastasis at 54 months. Regional axillary lymph node metastasis was not observed in five patients in whom lymph node dissection was performed, with a median of 14.2 dissected lymph nodes. Two of eight patients received preoperative chemo- or radiotherapy because of large tumor size; five of eight received postoperative radiotherapy. Local tumor control was achieved in six of eight patients. The median follow-up time was 53.9 months (3-168 months), of all survivors median 72.2 months. Recurrence and disease-free survival rates were analysed according to histologic grade, tumor size, stage, surgical and adjuvant treatment. PMID- 8436243 TI - Serum CA-15.3 and CEA patterns in postsurgical follow-up, and in monitoring clinical course of metastatic cancer in patients with breast carcinoma. AB - Serum CA-15.3 and CEA levels were longitudinally determined in 307 patients with breast carcinoma during postsurgical follow-up and/or therapy. Of 120 patients with no apparent disease, the specificity of marker levels fluctuating within the normal range (true-negative) was 98% for CA-15.3 alone (P = 0.004) and about 88% for CEA alone or for the tests combined. However, the false-negative levels in patients with progressive cancer reduced the predictive value of the tandem to around 76%, i.e. normal levels of both markers correctly predicted uneventful postsurgical course in only three fourths of the patients. Of 187 patients with active disease, the sensitivity of raised or increasing marker levels was around 70% for CA-15.3 alone or CEA alone, and 82% for the tests combined (P = 0.006). The 11% false-positive rate of CEA in patients with no apparent disease decreased the predictive value of a positive test from 98% for CA-15.3 alone (P = 0.006) to 91% for CEA alone or the tandem. Serum CA-15.3 or CEA paralleled the site of relapse: at least one marker was found elevated in 60% of patients with locoregional disease or with metastases to the lungs or bones exclusively, and in 90% of those with metastases to the lungs and bones or to the liver. A concurrent decrease of both marker levels reflected response to therapy while an increase of at least one marker level reflected treatment failure. It may be concluded that the marker tandem was better than either marker alone for follow-up aimed at detection of relapse, and that the tests were approximately 80% accurate for follow-up and/or monitoring therapy. PMID- 8436244 TI - Complications of rectus abdominis myocutaneous flaps in breast surgery. AB - One-hundred-and-twenty-two rectus abdominis myocutaneous flaps used for reconstruction, post mastectomy (106) and after salvage surgery (16), were reviewed. The minimum period of follow up was 24 months. Simple vertical flaps were raised in 88 patients; in addition seven Drevers, four trans-umbilical, 19 lower transverse and four combined (vertical and transverse flaps) were raised. Early complications (within 2 weeks of surgery) were seen in 30% (37/122) patients. Late complications occurred in 5% of patients (6/122) and 8% had both early and late complications. Flap necrosis was seen in 25% (21/122) of patients. This comprised complete flap loss in two patients. Partial skin and fat necrosis was observed in 14 patients and partial skin loss only in 15. In the group with simple vertical flaps the incidence of partial flap necrosis was 12.5%. Late complications included incisional hernia in 5% of patients. Reoperation for complications were required in 18% of patients. We conclude that while minor morbidity is common with rectus flaps, major complications are few. The more important considerations relate to cigarette smoking and overuse of the peripheral segment of the transverse rectus abdominis flap. While the transverse flaps have now largely replaced other breast flaps, in our practice vertical and higher transverse flaps were useful alternatives. Lessons learned during the development of these flaps have led to greatly improved results in the latter part of the series and it is regarded as a versatile and useful flap in this situation. PMID- 8436245 TI - Osteoclast-type giant cell tumor of the pancreas associated with mucinous cystadenoma. AB - Osteoclast-type giant cell tumor of the pancreas is a rare form of pancreatic malignancy. This present case is the first instance where an osteoclast type giant cell tumor is reported in association with a pancreatic mucinous cystadenoma. PMID- 8436246 TI - Malignant haemangiopericytoma of the chest wall. AB - A patient with malignant haemangiopericytoma of the right second rib is described. En-bloc resection of this rare tumour with the adjacent upper lobe of the lung and part of the chest wall could be achieved. The clinical and morphologic features of this case are presented. On account of the high risk of local recurrence and distant metastasis, we think an adjuvant chemo- and radiotherapy is indicated. PMID- 8436247 TI - Metastatic carcinoid of the breast: an unusual screen-detected breast cancer. AB - The breast is a rare site of metastasis. This case report is of a rare case of metastatic carcinoid tumour to the breast. The differentiation from primary breast carcinoid is discussed. PMID- 8436248 TI - Pancreatic insufficiency secondary to abdominal radiotherapy. AB - Delayed post-irradiation steatorrhoea secondary to acute pancreatic insufficiency is rare. We describe a case occurring in a patient 23 years following radical abdominal radiotherapy for testicular seminoma. PMID- 8436249 TI - Abnormal insulin secretion and glucose metabolism in pancreatic islets from the spontaneously diabetic GK rat. AB - Insulin secretion and islet glucose metabolism were compared in pancreatic islets isolated from GK/Wistar (GK) rats with spontaneous Type 2 (non-insulin-dependent) diabetes mellitus and control Wistar rats. Islet insulin content was 24.5 +/- 3.1 microU/ng islet DNA in GK rats and 28.8 +/- 2.5 microU/ng islet DNA in control rats, with a mean (+/- SEM) islet DNA content of 17.3 +/- 1.7 and 26.5 +/- 3.4 ng (p < 0.05), respectively. Basal insulin secretion at 3.3 mmol/l glucose was 0.19 +/- 0.03 microU.ng islet DNA-1.h-1 in GK rat islets and 0.04 +/- 0.07 in control islets. Glucose (16.7 mmol/l) stimulated insulin release in GK rat islets only two-fold while in control islets five-fold. Glucose utilization at 16.7 mmol/l glucose, as measured by the formation of 3H2O from [5-3H]glucose, was 2.4 times higher in GK rat islets (3.1 +/- 0.7 pmol.ng islet DNA-1.h-1) than in control islets (1.3 +/- 0.1 pmol.ng islet DNA-1.h-1; p < 0.05). In contrast, glucose oxidation, estimated as the production of 14CO2 from [U-14C]glucose, was similar in both types of islets and corresponded to 15 +/- 2 and 30 +/- 3% (p < 0.001) of total glucose phosphorylated in GK and control islets, respectively. Glucose cycling, i.e. the rate of dephosphorylation of the total amount of glucose phosphorylated, (determined as production of labelled glucose from islets incubated with 3H2O) was 16.4 +/- 3.4% in GK rat and 6.4 +/- 1.0% in control islets, respectively (p < 0.01). We conclude that insulin secretion stimulated by glucose is markedly impaired in GK rat islets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8436250 TI - Dietary fish oil augments nitric oxide production or release in patients with type 2 (non-insulin-dependent) diabetes mellitus. AB - Decreased release of nitric oxide from damaged endothelium is responsible for the impaired endothelium-dependent vasodilator responses found in animal models of vascular disease. Dietary supplementation with fish oils has been shown to augment endothelium-dependent relaxations, principally by improving the release of nitric oxide from injured endothelium. Using forearm venous occlusion plethysmography we studied vascular responses to 60, 120, 180 and 240 nmol/min of acetylcholine (an endothelium-dependent vasodilator) and 3, 6 and 9 nmol/min of glyceryl trinitrate (an endothelium-independent vasodilator) infused into the brachial artery in 23 patients with Type 2 (non-insulin-dependent) diabetes mellitus. NG monomethyl-L-arginine was employed to inhibit stimulated and basal release of nitric oxide from the endothelium. On completion of the baseline studies patients randomly received either fish oil or matching olive oil capsules in a double-blind crossover fashion for 6 weeks followed by a 6-week washout period and a final 6-week treatment phase. Studies, identical to the initial baseline studies, were performed at the end of the active treatment periods at 6 and 18 weeks. Fish oil supplementation significantly improved forearm blood flow responses to each dose of acetylcholine when compared to the vasodilator responses recorded at baseline and after olive oil administration (p < 0.01). Neither fish oil nor olive oil supplementation produced any significant changes in forearm blood flow to the incremental infusions of glyceryl trinitrate when compared with responses recorded during the baseline studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8436251 TI - Human autoantibodies react with glutamic acid decarboxylase antigen in human and rat but not in mouse pancreatic islets. AB - The presence of one of the major targets for autoantibodies in Type 1 (insulin dependent) diabetes mellitus, the enzyme glutamic acid decarboxylase, was studied in human, rat and mouse pancreatic tissue using immunoprecipitation and immunohistochemical techniques. Immunoprecipitation of glutamic acid decarboxylase was attempted with lysates of [35S]-methionine-labelled rat or mouse pancreatic islets using two different glutamic acid decarboxylase antisera, one mouse monoclonal antibody raised against the 65 kDa isoform of the enzyme, sera from six patients with Type 1 diabetes, one patient with stiff-man syndrome and sera from 19 non-obese diabetic mice. The same sera were used for immunoperoxidase staining of cryosections of human, rat or mouse pancreas. Using patient sera glutamic acid decarboxylase was detected by immunoprecipitations from isolated rat islets but not from islets of five different mouse strains tested, including the non-obese diabetic mouse. When using the non-obese diabetic mouse sera, glutamic acid decarboxylase could not be detected in either rat or mouse tissue. Immunoperoxidase staining demonstrated high levels of glutamic acid decarboxylase in human and rat pancreatic islets but low levels in mouse islets. Direct measurements of enzyme activity showed glutamic acid decarboxylase to be present in mouse islets at a level of about 40% of that in rat islets, and subsequent Western blot analyses indicated that mouse islets express the 67 kDa isoform, whereas as in rat islets both the 67 and 65 kDa isoforms are present.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8436252 TI - Plasma lipoprotein (a) concentration and phenotypes in diabetes mellitus. AB - Patients with Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes mellitus are at increased risk of developing atherosclerotic vascular diseases. A variety of lipoprotein abnormalities have been described as being associated with this increased risk. In this study, apo(a) isoform frequencies and lipoprotein(a) [Lp(a)] concentrations were determined in Type 1 and Type 2 diabetic patients in order to investigate a possible contribution of Lp(a) to the increased risk for atherosclerosis in diabetes. No significant differences in plasma Lp(a) concentrations were found in two ethnically different populations (Austrians from the province of Tyrol and Hungarians from Budapest) in either type of diabetes when compared to respective control groups (91 Type 1 and 112 Type 2 diabetic patients vs 202 control subjects in the Hungarian study and 44 Type 1 diabetic and 44 Type 2 diabetic vs 125 control subjects in the Austrian study). There were also no significant apo(a) isoform frequency differences between both patient groups and control subjects in the two study groups. These data, obtained from two large ethnically different populations, provide no evidence of a contribution of Lp(a) to the increased risk for atherosclerosis in diabetes. PMID- 8436253 TI - Erythrocyte sodium-lithium countertransport activity and total body insulin mediated glucose disposal in normoalbuminuric normotensive type 1 (insulin dependent) diabetic patients. AB - Insulin resistance in Type 1 (insulin-dependent) diabetes mellitus may be associated with raised erythrocyte sodium-lithium countertransport activity in patients with hypertension, or nephropathy, or both. However, in these circumstances it is difficult to separate the impact of hypertension, hyperlipidaemia and nephropathy on erythrocyte sodium-lithium countertransport from that of insulin resistance. We have therefore examined the relationship between insulin-mediated glucose disposal and erythrocyte sodium-lithium countertransport in 41 normotensive (mean blood pressure 120/74 mmHg), normoalbuminuric (mean albumin excretion 6.2 micrograms/min), normolipidaemic (mean serum cholesterol 4.3 mmol/l and mean serum triglycerides 1.0 mmol/l) Type 1 diabetic patients. Erythrocyte sodium-lithium countertransport was on average 0.31 mmol Li.h-1.l erythrocytes-1 (range 0.07-0.69). Nine patients had values above 0.40 mmol Li.h-1.l erythrocytes-1 (0.51 +/- 0.10 mmol Li.h-1.l erythrocytes 1). The patients with high erythrocyte sodium-lithium countertransport were matched for age, sex, BMI, HbA1 and duration of diabetes, with nine patients with normal erythrocyte sodium-lithium countertransport. Insulin-mediated glucose disposal was evaluated during the last hour of a euglycaemic clamp (insulin 0.015 U.kg-1.h-1; blood glucose clamped at 7.0 mmol/l). The free insulin levels were comparable between the patients with high and normal erythrocyte sodium-lithium countertransport (37.2 +/- 14.7 mU/l and 34.7 +/- 17.2 mU/l respectively). Insulin-mediated glucose disposal was on average 3.1 +/- 1.5 (range 0.8-6.8) mg.kg-1.min-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8436254 TI - Transcapillary escape rate of albumin in hypertensive patients with type 1 (insulin-dependent) diabetes mellitus. AB - Diabetic patients with elevated urinary albumin excretion rate (incipient or clinical nephropathy) also have an increased transcapillary escape rate of albumin. This study was designed to clarify whether this is caused by a general vascular dysfunction or by elevated systemic blood pressure. The systemic blood pressure and the transcapillary escape rate of albumin were measured in the following groups after 4 weeks without antihypertensive treatment: Group 1- eleven healthy control subjects. Group 2--ten Type 1 (insulin-dependent) diabetic patients with incipient nephropathy (urinary albumin excretion rate: 30-300 mg/24 h) and normal blood pressure. Group 3--eleven non-diabetic patients with essential hypertension. Group 4--nine Type 1 diabetic patients with hypertension but normal urinary albumin excretion (< 30 mg/24 h). Group 5--eleven Type 1 diabetic patients with nephropathy (urinary albumin excretion rate > 300 mg/24 h) and hypertension. Systolic and diastolic blood pressure were similar in the three hypertensive groups: group 3, 148 +/- 8/95 +/- 6; group 4, 150 +/- 12/94 +/- 8 and group 5; 152 +/- 12/92 +/- 7 mmHg, but significantly elevated (p < 0.001) compared to control group 1, 117 +/- 12/74 +/- 9 and group 2, 128 +/- 7/82 +/- 4 mmHg. The transcapillary escape rate of albumin was similar in the control subjects (5.2 +/- 2.7%) and the subjects in the normoalbuminuric groups 3 and 4 (6.2 +/- 1.9 and 5.1 +/- 1.4%, respectively) and significantly lower (p < 0.001) than in patients with elevated urinary albumin excretion without or with hypertension group 2, 10.1 +/- 2.8 and group 5, 11.4 +/- 5.7%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8436255 TI - Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. AB - Two follow-up studies were carried out to determine whether lower birthweight is related to the occurrence of syndrome X-Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia. The first study included 407 men born in Hertfordshire, England between 1920 and 1930 whose weights at birth and at 1 year of age had been recorded by health visitors. The second study included 266 men and women born in Preston, UK, between 1935 and 1943 whose size at birth had been measured in detail. The prevalence of syndrome X fell progressively in both men and women, from those who had the lowest to those who had the highest birthweights. Of 64-year-old men whose birthweights were 2.95 kg (6.5 pounds) or less, 22% had syndrome X. Their risk of developing syndrome X was more than 10 times greater than that of men whose birthweights were more than 4.31 kg (9.5 pounds). The association between syndrome X and low birthweight was independent of duration of gestation and of possible confounding variables including cigarette smoking, alcohol consumption and social class currently or at birth. In addition to low birthweight, subjects with syndrome X had small head circumference and low ponderal index at birth, and low weight and below-average dental eruption at 1 year of age. It is concluded that Type 2 diabetes and hypertension have a common origin in sub-optimal development in utero, and that syndrome X should perhaps be re-named "the small-baby syndrome". PMID- 8436256 TI - Nerve function and its determinants in patients with newly-diagnosed type 2 (non insulin-dependent) diabetes mellitus and in control subjects--a 5-year follow-up. AB - In order to assess the changes in nerve function 5 years after the diagnosis of diabetes mellitus and the determinants of progression of neuropathy, we studied 113 Type 2 (non-insulin-dependent) diabetic patients and 127 non-diabetic control subjects. Motor and sensory nerve conduction velocities were measured at the time of diagnosis of diabetes and 5 years later. At both examinations conduction velocities and response amplitudes were lower in diabetic patients than in control subjects. During the follow-up sural nerve conduction was impaired in both diabetic and control subjects, but, in general, changes in neurophysiological parameters were slight and inconsistent. In 12 diabetic patients nerve function deteriorated significantly during the follow-up. These patients had higher glycaemic indices at both examinations and lower baseline blood pressure levels as compared to the rest of the diabetic patients. No differences between these patient groups were found in other baseline risk factors (age, obesity, use of alcohol, smoking, serum insulin levels, albuminuria, lipids). In conclusion, Type 2 diabetic patients have disturbed nerve function at the time of diagnosis, but neurophysiological impairment during the next 5 years is on the average slight. Poor glycaemic control seems to be the most important risk factor in the deterioration of nerve function in these patients. PMID- 8436257 TI - Symmetry of cerebral blood flow and cognitive responses to hypoglycaemia in humans. AB - A low blood glucose level is associated with impairment of higher cerebral function and an increase in cerebral blood flow. This study examined whether there are differences in the physiological responses to hypoglycaemia between the cerebral hemispheres. Eight healthy men participated in two hyperinsulinaemic glucose clamp studies: after 60 min at 4.5 mmol/l, blood glucose was either lowered to 2.0 mmol/l and "clamped" there for 60 min (hypoglycaemia) or continuously maintained at 4.5 mmol/l (euglycaemia). Cardiac output, middle cerebral artery velocity (transcranial Doppler) and cerebral blood flow (133 xenon inhalation) were measured during the studies. Neuropsychological tests were used to determine whether hypoglycaemia caused differential impairment of hemispheric cognitive function. Hypoglycaemia was associated with symmetrical impairment of cognitive function in both cerebral hemispheres and a rise in cardiac output (from 5.5 [0.2] to 8.7 [0.2] l.min-1, p < 0.0001, mean [standard error]), middle cerebral artery velocity (from 55 [2.6] to 64 [2.8] cm.s-1, p < 0.002), and global cerebral blood flow (from 56 [2.6] to 69 [2.9] ml.100 g-1.min 1, p < 0.005 compared to pre-insulin values). There were no differences in the blood flow response during hypoglycaemia between hemispheres and the increase in blood flow did not correlate with either the change in cardiac output or rise in plasma catecholamine levels. After 120 min of hyperinsulinaemic, euglycaemia, global cerebral blood flow rose significantly above baseline (from 58 [2.4] to 63 [2.2] ml.100 g-1.min-1, p < 0.05). In conclusion, using the techniques described, the physiological and cognitive responses of each cerebral hemisphere to hypoglycaemia were symmetrical.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8436259 TI - Effect of dexamethasone on insulin sensitivity, islet amyloid polypeptide and insulin secretion in humans. AB - The response of islet amyloid polypeptide and insulin and their molar ratios were investigated in eight healthy volunteers before and after treatment with dexamethasone by oral and frequently-sampled intravenous glucose tolerance tests. Following dexamethasone treatment the insulin sensitivity index decreased significantly from 6.5 +/- 1.3 to 4.1 +/- 1.0 (microU.ml-1).min-1, p < 0.05. The area under the curve representing above-basal levels of insulin during oral glucose tolerance test increased significantly following dexamethasone treatment from 48132 +/- 9736 to 82230 +/- 14846 pmol.l-1 x 3 h-1, p < 0.05, the area under the curve of islet amyloid polypeptide increased from 1308 +/- 183 to 2448 +/- 501 pmol.l-1 x 3 h-1, p < 0.05. The overall insulin/islet amyloid polypeptide molar ratios calculated from the area under the curve during the 3-h period of the oral glucose tolerance test was not significantly different before and after dexamethasone treatment (42 +/- 5 vs 40 +/- 4). During the oral glucose tolerance test the insulin/islet amyloid polypeptide ratio increased significantly from baseline to 30 min (p < 0.05), then declined towards initial values before and after dexamethasone treatment. In conclusion, dexamethasone induced a significant decrease in insulin sensitivity and a significant increase in insulin secretion during the oral glucose tolerance test. However, in contrast to previous animal experiments we did not find a change in the insulin/islet amyloid polypeptide ratio before and after dexamethasone treatment. PMID- 8436258 TI - Stiffening of connective tissue in elderly diabetic patients: relevance to diabetic nephropathy and oxidative stress. AB - Limited joint mobility seen in diabetes mellitus is thought to be the result of stiffening of periarticular connective tissue, which is presumably derived from increased cross-linking of collagen related to advanced glycation end products. In this study the extent of the stiffening of connective tissue was measured by the passive extension angle of the metacarpophalangeal joints in 205 elderly diabetic patients. Association with diabetic nephropathy, with which advanced glycation end products have recently been demonstrated to increase, and metabolic abnormalities were also considered. The angle of the metacarpophalangeal joints was significantly correlated with age (r = -0.24, p < 0.01), and was significantly smaller in men than in women (p < 0.01). The angle demonstrated a decrease in association with diabetic retinopathy and nephropathy, and only the association with nephropathy was significant (p < 0.05). The angle was weakly, but significantly, correlated with serum thiobarbituric acid reactants as a measure of lipid peroxides (r = -0.15, p < 0.05), triglyceride (r = -0.20, p < 0.01) and HDL cholesterol (r = 0.19, p < 0.01), but not with blood glucose (r = 0.02), HbA1c (r = 0.06) or duration of diabetes (r = -0.05). In addition, the angle in 14 non-diabetic patients on haemodialysis was significantly (p < 0.05) smaller than that in age- and sex-matched normal subjects. Thus, it was indicated that the stiffening of connective tissue was associated with diabetic nephropathy, serum lipid peroxide and dyslipidaemia. Stiffening of connective tissue seems to be more affected by oxidative stress than non-enzymatic glycation per se.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8436260 TI - Raised serum apolipoprotein (a) in active diabetic retinopathy. AB - Progressive capillary occlusion often leads to severe retinopathy within 15-20 years of the onset of Type 1 (insulin-dependent) diabetes mellitus. Lipoprotein(a), a complex formed by apolipoprotein(a), apo B-100 and lipids, is considered an independent, genetically determined, predictor of cardiovascular disease. It may have antifibrinolytic properties in view of its similarity to plasminogen. To test the hypothesis that circulating lipoprotein(a) is associated with the process that leads to clinically active diabetic retinopathy, we measured the circulating levels of apolipoprotein(a) (which are strictly correlated with those of lipoprotein(a)) in two groups of patients with Type 1 diabetes of at least 15 years duration: 25 with active retinopathy and 27 without clinically detectable retinal lesions. Thirty-eight healthy subjects of the same age and sex served as controls. Serum apolipoprotein(a) was higher in the patients with active retinopathy (36(2-193) U/dl, geometric mean and range) than in those without clinically detectable retinal lesion (17(1-160)) and the control subjects (14(0-115)), p < 0.01 in both cases. The distribution of apolipoprotein(a) levels was skewed to the left, as expected, in the patients without clinically evident retinal lesions and the control groups, but there was a bimodal trend of distribution among those with active retinopathy. The levels of glycated haemoglobin were similar in the two groups of diabetic patients, and no significant differences were found for total and HDL cholesterol, triglycerides or apolipoproteins A1 and B between them and the control subjects. These preliminary results suggest that serum apolipoprotein(a) is elevated in patients with active retinopathy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8436261 TI - Visceral fat deposition is seen in patients with insulinoma. PMID- 8436262 TI - Subtype of islet cell antibodies and slowly progressive beta-cell failure. PMID- 8436263 TI - Quantitative genetics in Edinburgh: 1947-1980. PMID- 8436264 TI - The effects of central asymmetry on the propagation of palindromic DNA in bacteriophage lambda are consistent with cruciform extrusion in vivo. AB - The propagation of lambda phages carrying long perfect palindromes has been compared with that of phages carrying imperfect palindromes with small regions of central asymmetry. The perfect palindromes confer a more deleterious phenotype than those with central asymmetry and the severity of the phenotype declines with the length of asymmetry in the range from O to 27 base pairs. These results argue that a center-dependent reaction is involved in the phenotypic effects of palindromic DNA sequences, consistent with the idea that cruciform extrusion occurs in vivo. PMID- 8436265 TI - Meiotic nondisjunction and recombination of chromosome III and homologous fragments in Saccharomyces cerevisiae. AB - A yeast strain, in which nondisjunction of chromosome III at the first meiotic division could be assayed, was constructed. Using chromosome fragmentation plasmids, chromosomal fragments (CFs) were derived in isogenic strains from six sites along chromosome III and one site on chromosome VII. Whereas the presence of the CFs derived from chromosome III increased considerably the meiosis I nondisjunction of that chromosome, the CF derived from chromosome VII had no effect on chromosome III segregation. The effects of the chromosome III-derived fragments were not linearly related to fragment length. Two regions, one of 12 kb in size located at the left end of the chromosome, and the other of 5 kb, located at the center of the right arm, were found to have profound effects on chromosome III nondisjunction. Most disomics arising from meioses in strains containing chromosome III CFs did not contain the CF; thus it appears that the two chromosome III homologs had segregated away from the CF. Among the disomics, recombination between the homologous chromosomes III was lower than expected from the genetic distance, while recombination between one of the chromosomes III and the fragment was frequent. We suggest that there are sites along the chromosome that are more involved than others in the pairing of homologous chromosomes and that the pairing between fragment and homologs involves recombination among these latter elements. PMID- 8436266 TI - A short chromosomal region with major roles in yeast chromosome III meiotic disjunction, recombination and double strand breaks. AB - A multicopy plasmid was isolated from a yeast genomic library, whose presence resulted in a twofold increase in meiotic nondisjunction of chromosome III. The plasmid contains a 7.5-kb insert from the middle of the right arm of chromosome III, including the gene THR4. Using chromosomal fragments derived from chromosome III, we determined that the cloned region caused a significant, specific, cis acting increase in chromosome III nondisjunction in the first meiotic division. The plasmid containing this segment exhibited high spontaneous meiotic integration into chromosome III (in 2.4% of the normal meiotic divisions) and a sixfold increase (15.5%) in integration in nondisjunctant meioses. Genetic analysis of the cloned region revealed that it contains a "hot spot" for meiotic recombination. In DNA of rad50S mutant cells, a strong meiosis-induced double strand break (DSB) signal was detected in this region. We discuss the possible relationships between meiosis-induced DSBs, recombination and chromosome disjunction, and propose that recombinational hot spots may be "pairing sites" for homologous chromosomes in meiosis. PMID- 8436268 TI - Conditional mutations in the yeast DNA primase genes affect different aspects of DNA metabolism and interactions in the DNA polymerase alpha-primase complex. AB - Different pri1 and pri2 conditional mutants of Saccharomyces cerevisiae altered, respectively, in the small (p48) and large (p58) subunits of DNA primase, show an enhanced rate of both mitotic intrachromosomal recombination and spontaneous mutation, to an extent which is correlated with the severity of their defects in cell growth and DNA synthesis. These effects might be attributable to the formation of nicked and gapped DNA molecules that are substrates for recombination and error-prone repair, due to defective DNA replication in the primase mutants. Furthermore, pri1 and pri2 mutations inhibit sporulation and affect spore viability, with the unsporulated mutant cells arresting with a single nucleus, suggesting that DNA primase plays a critical role during meiosis. The observation that all possible pairwise combinations of two pri1 and two pri2 alleles are lethal provides further evidence for direct interaction of the primase subunits in vivo. Immunopurification and immunoprecipitation studies on wild-type and mutant strains suggest that the small subunit has a major role in determining primase activity, whereas the large subunit directly interacts with DNA polymerase alpha, and either mediates or stabilizes association of the p48 polypeptide in the DNA polymerase alpha-primase complex. PMID- 8436267 TI - Telomere-mediated plasmid segregation in Saccharomyces cerevisiae involves gene products required for transcriptional repression at silencers and telomeres. AB - Plasmids that contain Saccharomyces cerevisiae TG1-3 telomere repeat sequences (TRS plasmids) segregate efficiently during mitosis. Mutations in histone H4 reduce the efficiency of TRS-mediated plasmid segregation, suggesting that chromatin structure is involved in this process. Sir2, Sir3 and Sir4 are required for the transcriptional repression of genes located at the silent mating type loci (HML and HMR) and at telomeres (telomere position effect) and are also involved in the segregation of TRS plasmids, indicating that TRS-mediated plasmid segregation involves factors that act at chromosomal telomeres. TRS plasmid segregation differes from the segregation of plasmids carrying the HMR E silencing region: HMR E plasmid segregation function is completely dependent upon Sir2, Sir3 and Sir4, involves Sir1 and is not influenced by mutations in RAP 1 that eliminate TRS plasmid segregation. Mutations in SIR1, SIN1, TOP1, TEL1 and TEL2 do not influence TRS plasmid segregation. Unlike transcriptional repression at telomeres, TRS plasmids retain partial segregation function in sir2, sir3, sir4, nat1 and ard1 mutant strains. Thus it is likely that TRS plasmid segregation involves additional factors that are not involved in telomere position effect. PMID- 8436269 TI - Insertional mutagenesis in Neurospora crassa: cloning and molecular analysis of the preg+ gene controlling the activity of the transcriptional activator NUC-1. AB - The transcriptional activator NUC-1 controls the transcription of the genes for phosphorus acquisition enzymes, and its activity is regulated by the negative regulatory factors, PREG and PGOV In this report, we describe the cloning and molecular analysis of the preg+ gene. In Neurospora crassa, as in higher eukaryotes, transformation frequently results in nonhomologous integration of transforming DNA. Insertion of transforming DNA into host genes mutates the gene and provides a molecular tag for cloning it. We obtained two mutants that have an insertion in the preg+ and pgov+ genes, respectively, among 2 x 10(5) transformants. The preg+ gene was cloned by screening a Neurospora genomic DNA library with DNA sequences flanking the transforming DNA of the rescued plasmid. Northern analysis showed that the transcription of the preg+ gene is not regulated by phosphate. The carboxy-terminal half of PREG shows strong homology with Saccharomyces cerevisiae PHO80 whose function is analogous to that of PREG. The pregc mutations are located in the well conserved residues which may directly interact with the residues in the regulatory domain of NUC-1. PMID- 8436270 TI - Frequent changes in the number of reiterated ribosomal RNA genes throughout the life cycle of the basidiomycete Coprinus cinereus. AB - We have examined the stability of the tandemly repeated genes that encode the ribosomal RNA in Coprinus cinereus. These genes are contained within two linked HindIII fragments in a 3.0-Mb chromosome. We monitored the size of these fragments in both mitotic and meiotic segregants using the contour-clamped homogeneous electric field (CHEF) method. No length changes were observed in the smaller HindIII fragment (100 kb; 10 repeats) among the DNAs prepared from 46 asexual spore derivatives (oidia) or 128 meiotic segregants (basidiospores from 32 tetrads). However, the larger HindIII fragment (1100 kb; 120 repeats) did exhibit variability. Substantial changes, involving up to 40% of the larger HindIII fragment were recorded in 7 of 46 oidial isolates (including 4 of 22 transformed derivatives). To learn if the changes were confined to the vegetative portion of the life cycle, we examined transmission of HindIII variants through three crosses. In the first two crosses (16 tetrads total), no changes were observed in the large HindIII fragment. However, in the third cross (16 tetrads), each tetrad showed at least one alteration. In half of the tetrads from the third cross, the altered patterns segregated 2:2, suggesting that the changes occurred after mating but prior to premeiotic DNA replication. We conclude that breakage and rejoining reactions within the rDNA are frequent and are not confined to any particular stage of the life cycle. It also appears that certain repeats are sheltered from these events. Finally, marked differences in rDNA stability were observed in the cross analyzed. PMID- 8436271 TI - A genetic system controlling mitochondrial fusion in the slime mould, Physarum polycephalum. AB - We have identified two distinct mitochondrial phenotypes, namely, Mif+ (mitochondrial fusion) and Mif- (mitochondrial fusion-deficient), and have studied the genetic system that controls mitochondrial fusion in the slime mould, Physarum polycephalum. A mitochondrial plasmid of approximately 16 kbp was identified in all Mif+ plasmodial strains. This plasmid is apparently responsible for promoting mitochondrial fusion, and it is inserted into the mitochondrial DNA (mtDNA) in successive sexual crossing with Mif- strains. This recombinant mtDNA and the unchanged free plasmid spread through the mitochondrial population via the promotion of mitochondrial fusion. The Mif+ strains with the plasmid were further classified as being two types: high frequency and low frequency mitochondrial fusion. Restriction analysis of the mtDNA suggested that the high frequency mitochondrial fusion type was more often heteroplasmic; within each plasmodium, mtDNAs of both parental types were usually present, in addition to the presence of the plasmid. Genetic analysis with the progeny obtained from crossing myxamoebae derived from three different isolates suggested that these progeny carried different alleles at a nuclear locus that controlled the frequency of mitochondrial fusion. These alleles (mitochondrial mating-type alleles, mitA1, 2 and 3) appear to function like the mating type of the myxamoebae; mitochondrial fusion occurs at high frequency with the combination of unlike alleles, but at low frequency with the combination of like alleles. PMID- 8436272 TI - Post-transcriptional regulation of RNA polymerase II levels in Caenorhabditis elegans. AB - To investigate the regulation of RNA polymerase II levels in Caenorhabditis elegans, we have constructed nematode strains having one, two, or three copies of ama-1, the gene for the largest subunit of RNA polymerase II. Steady-state levels of RNA polymerase II polypeptides and solubilized enzyme activity are invariant with gene dosage, indicating regulatory compensation. However, steady-state levels of ama-1 mRNA are directly proportional to gene dosage. These results imply that RNA polymerase II levels in C. elegans are regulated post transcriptionally. PMID- 8436273 TI - Conflict between feminizing sex ratio distorters and an autosomal masculinizing gene in the terrestrial isopod Armadillidium vulgare Latr. AB - Female sex determination in the pill bug Armadillidium vulgare is frequently under the control of feminizing parasitic sex factors (PSF). One of these PSF is an intracytoplasmic Wolbachia-like bacterium (F), while the other (f) is suspected of being an F-bacterial DNA sequence unstably integrated into the host genome. In most wild populations harboring PSF, all individuals are genetic males (ZZ), and female phenotypes occur only due to the presence of PSF which overrides the male determinant carried by the Z chromosome (females are thus ZZ +F or ZZ +f neo-females). Here we report the effects of the conflict between these PSF and a dominant autosomal masculinizing gene (M) on phenotypes. The M gene is able to override the feminizing effect of the f sex factor and, consequently, male sex may be restored. However, M is unable to restore male sex when competing with the F bacteria. It seems that the main effect of M is to delay the expression of F bacteria slightly, inducing intersex phenotypes. Most of these intersexes are functional females, able to transmit the masculinizing gene. The frequency of M and its effects on the sex ratio in wild populations are discussed. PMID- 8436274 TI - Structure and expression of hybrid dysgenesis-induced alleles of the ovarian tumor (otu) gene in Drosophila melanogaster. AB - Mutations at the ovarian tumor (otu) gene of Drosophila melanogaster cause female sterility and generate a range of ovarian phenotypes. Quiescent (QUI) mutants exhibit reduced germ cell proliferation; in oncogenic (ONC) mutants germ cells undergo uncontrolled proliferation generating excessive numbers of undifferentiated cells; the egg chambers of differentiated (DIF) mutants differentiate to variable degrees but fail to complete oogenesis. We have examined mutations caused by insertion and deletion of P elements at the otu gene. The P element insertion sites are upstream of the major otu transcription start sites. In deletion derivatives, the P element, regulatory regions and/or protein coding sequences have been removed. In both insertion and deletion mutants, the level of otu expression correlates directly with the severity of the phenotype: the absence of otu function produces the most severe QUI phenotype while the ONC mutants express lower levels of otu than those which are DIF. The results of this study demonstrate that the diverse mutant phenotypes of otu are the consequence of different levels of otu function. PMID- 8436275 TI - Genetic and molecular characterization of P element-induced mutations reveals that the Drosophila ovarian tumor gene has maternal activity and a variable null phenotype. AB - The mutations in the ovarian tumor (otu) gene arrest oogenesis at several stages in development. A series of deletion mutations in the otu region were characterized, each of which causes the absence or reduction of the otu transcript. These alleles range from the most severe class, which results in ovaries lacking egg cysts, to relatively mild mutations that allow the development of late stage oocytes. Heteroallelic combinations of these mutations demonstrate that the phenotypic complexity of otu mutant ovaries is due to a dosage dependent requirement for otu activity. Reciprocal cross and developmental Northern blot studies suggest a maternal requirement for otu in the development of the female germline. In addition we demonstrate that the otu zygotic null phenotype is variable, ranging from the absence of cysts in the most extreme cases, to the presence of tumorous egg chambers. PMID- 8436276 TI - Hybrid lethal systems in the Drosophila melanogaster species complex. I. The maternal hybrid rescue (mhr) gene of Drosophila simulans. AB - Hybrid females from Drosophila simulans females x Drosophila melanogaster males die as embryos while hybrid males from the reciprocal cross die as late larvae. The other two classes are sterile adults. Letting C, X, and Y designate egg cytoplasm, X, and Y chromosomes, respectively, and subscripts m and s stand for melanogaster and simulans, CmXmYs males are lethal in the larval stage and are rescued by the previously reported genes, Lhr (Lethal hybrid rescue) in simulans or Hmr (Hybrid male rescue) in melanogaster. We report here another rescue gene located on the second chromosome of simulans, mhr (maternal hybrid rescue) that, when present in the mother, rescues CsXmXs females from embryonic lethality. It has been postulated that the hybrids not carrying the Xs like CmXmYs males are larval lethal and that the hybrids carrying both the Cs and the Xm like CsXmXs females are embryonic lethal. According to these postulates CsXmYs males (obtained by mating attached-X simulans females to melanogaster males) should be doubly lethal, at both embryo and larval stages. When both rescuing genes are present, Hmr in the father and mhr in the mother, males of this genotype are fully viable, as predicted. PMID- 8436277 TI - Hybrid lethal systems in the Drosophila melanogaster species complex. II. The Zygotic hybrid rescue (Zhr) gene of D. melanogaster. AB - Hybrid females from Drosophila simulans females x Drosophila melanogaster males die as embryos while hybrid males from the reciprocal cross die as larvae. We have recovered a mutation in melanogaster that rescues the former hybrid females. It was located on the X chromosome at a position close to the centromere, and it was a zygotically acting gene, in contrast with mhr (maternal hybrid rescue) in simulans that rescues the same hybrids maternally. We named it Zhr (Zygotic hybrid rescue). The gene also rescues hybrid females from embryonic lethals in crosses of Drosophila mauritiana females x D. melanogaster males and of Drosophila sechellia females x D. melanogaster males. Independence of the hybrid embryonic lethality and the hybrid larval lethality suggested in a companion study was confirmed by employing two rescue genes, Zhr and Hmr (Hybrid male rescue), in doubly lethal hybrids. A model is proposed to explain the genetic mechanisms of hybrid lethalities as well as the evolutionary pathways. PMID- 8436278 TI - DNA sequence variation at the period locus within and among species of the Drosophila melanogaster complex. AB - A 1.9-kilobase region of the period locus was sequenced in six individuals of Drosophila melanogaster and from six individuals of each of three sibling species: Drosophila simulans, Drosophila sechellia and Drosophila mauritiana. Extensive genealogical analysis of 174 polymorphic sites reveals a complex history. It appears that D. simulans, as a large population still segregating very old lineages, gave rise to the island species D. mauritiana and D. sechellia. Rather than considering these speciation events as having produced "sister" taxa, it seems more appropriate to consider D. simulans a parent species to D. sechellia and D. mauritiana. The order, in time, of these two phylogenetic events remains unclear. D. mauritiana supports a large number of polymorphisms, many of which are shared with D. simulans, and so appears to have begun and persisted as a large population. In contrast, D. sechellia has very little variation and seems to have experienced a severe population bottleneck. Alternatively, the low variation in D. sechellia could be due to recent directional selection and genetic hitchhiking at or near the per locus. PMID- 8436280 TI - Meiotic drive and unisexual hybrid sterility: a comment. PMID- 8436279 TI - Selection and the evolution of genetic life cycles. AB - The evolution of haploid and diploid phases of the life cycle is investigated theoretically, using a model where the relative length of haploid and diploid phases is under genetic control. The model assumes that selection occurs in both phases and that fitness in each phase is a function of the time spent in that phase. The equilibrium and stability conditions that allow for all-haploid, all diploid, or polyphasic life cycles are considered for general survivorship functions. Types of stable life cycles possible depend on the form of the viability selection. If mortality rates are constant, either haploidy or diploidy is the only stable life cycle possible. Departures from constant mortality can give qualitatively different results. For example, when survivorship in each phase is a linear, decreasing function of the time spent in the phase, stable haploid, diploid or polyphasic life cycles are possible. The addition of genetic variation at a coevolving viability locus does not qualitatively affect the outcome with respect to the maintenance of polyphasic cycles but can lead to situations where more than one life cycle is concurrently stable. These results show that trade-offs between the advantages of being diploid and of being haploid may help explain the patterns of life cycles found in nature and that the type of selection may be critical to determining the results. PMID- 8436281 TI - Obstacles to the care of patients with medical-psychiatric illness on general hospital psychiatry units. AB - Although patients with both physical and mental illness (combined illness) are common in general hospitals, psychiatric units have been traditionally reluctant to accept such patients for intensive psychiatric care. This article presents three case reports of patients with combined illness who were largely refused at psychiatric units despite stable vital signs, and discusses factors compelling and hindering psychiatric unit acceptance of such patients. Such patients can be managed on psychiatric units when hindering factors are addressed. The most critical factor is an ongoing collegial relationship with nonpsychiatrist consultant physicians and nurses. The psychiatric unit can improve its worth and reduce stigma and mystique within the general medical hospital by becoming more accepting of these patients. PMID- 8436282 TI - Cross-cultural differences in the care of patients with cancer. A review. AB - In order to assure optimal care of patients with chronic medical illnesses it is necessary to take into account the cultural factors that may influence health related behaviors. By using cancer as a model, this paper discusses the major cultural issues that should be considered in order to increase cultural sensitivity in the medical setting: family function, sex roles, language, disclosure of disease-related information, pain, attitudes towards illness and health practices, immigration, region, autonomy versus dependency, and death and bereavement. Case histories illustrating the relevance of such socio-cultural factors in the cancer setting are reported. PMID- 8436283 TI - The feasibility of smoking bans on psychiatric units. AB - We conducted a prospective study of a smoking ban on a general inpatient psychiatry service in response to staff concerns about the feasibility of a proposed hospital-wide ban. Demographic information, smoking history, and DSM III R diagnoses were obtained for consecutively admitted patients during two study conditions: smoking and nonsmoking. A log of p.r.n. medication, seclusion, restraint, elopement, incident reports, and smoking-related discharges was kept for each patient. Chi-square analysis of 232 patients for whom demographic, smoking, diagnostic, and log data were complete showed no significant differences between study conditions for demographic or diagnostic variables. Two-tailed t test analysis of the log data for these 232 patients showed no significant difference in disruptive incidents during smoking and nonsmoking conditions (p = 0.183). Fifty staff members answered pre- and post-ban questionnaires. Paired t test analysis demonstrated a significant change in staff attitude toward supporting the ban. These data indicate that smoking can be stopped on inpatient psychiatry units without increases in unit disruption or adverse effects on staff morale. PMID- 8436284 TI - The effects of culture on illness behavior and medical care. Asian and American differences. AB - This paper examines the effects of culture on illness behavior and medical care by contrasting the differences between American and Asian cultures. We examine the differences in definitions of self and patterns of self-other interaction between these two cultures and how these differences influence the interpretation of illness experience, illness behavior, and interactions among physicians, patients, and families. We propose that understanding the patients' self-concepts and patterns of self-other relationships, which are largely culturally determined, is essential for an objective understanding of the patients' experience of illness, and can profoundly affect the quality of the physician patient relationship and medical care. PMID- 8436285 TI - A review of the utilization of sedative-hypnotic drugs in a general hospital. AB - A retrospective review of 493 patients treated during a single month in a general hospital in mid-Michigan revealed that a majority (84.2%) of them received prescriptions for sedative-hypnotic drugs. These were p.r.n. in 66% of cases and routine prescriptions in the remainder. Prescriptions were equally distributed across the specialties: internal medicine 15%, surgery 23%, family practice 19%, psychiatry 22%, and OB/GYN 20%. Flurazepam was the most frequently prescribed drug (48.4%), followed by triazolam (24.6%) and temazepam (12.2%). Actual utilization rates were highest among psychiatric patients (85%) and lowest in obstetrics (33%). The therapeutic rationale for prescribing sedative hypnotic agents to hospitalized patients is discussed. PMID- 8436286 TI - Psychiatric illness in patients with severe treatment-resistant mastalgia. PMID- 8436287 TI - Use of tricyclic antidepressants to facilitate benzodiazepine discontinuation. PMID- 8436288 TI - Patient delay in cancer. A view from the crisis model. AB - Despite widespread cancer awareness programs, deleterious delays in seeking diagnosis and care for cancer are as prominent now as as they were 50 years ago. These delays may be seen as attempts to resolve or postpone the crisis brought on an individual by the suspicion of terminal illness. The use of denial-like processes in the cognitive appraisal employed to assess this crisis is influenced by a variety of personal, social, and physical factors. Case material is examined to discuss the integration of these factors by the crisis model of physical illness and to examine the implications of such an approach for earlier detection and treatment of cancer. PMID- 8436289 TI - Synergism in transcriptional activation: a kinetic view. PMID- 8436290 TI - Factors (TAFs) required for activated transcription interact with TATA box binding protein conserved core domain. AB - TFIID is a multisubunit protein containing the TATA box-binding polypeptide (TBP) and associated factors (TFIID-TAFs) required for activated transcription by RNA polymerase II. TBPs from different eukaryotes contain a highly conserved carboxy terminal domain and very divergent amino-terminal domains. Earlier studies proposed that the amino-terminal domains of metazoan TBPs are required for activated transcription. However, we report that a human TFIID complex containing an amino-terminal truncated TBP contains all the major TFIID-TAFs and supports in vitro transcriptional stimulation by different classes of activation domains and from a TATA-less promoter. Protein blotting experiments revealed direct interactions between the conserved domain of TBP and the two largest TAFs. The results suggest a model for the interaction of TFIID-TAFs with TBP. PMID- 8436291 TI - Jun family members are controlled by a calcium-regulated, cyclosporin A-sensitive signaling pathway in activated T lymphocytes. AB - The octamer-binding transcription factor Oct-1 is involved in a wide variety of cellular processes but appears to lack a strong transcriptional activation domain, suggesting that it functions in the context of other proteins. We demonstrated previously that Oct-1, in association with a 40-kD protein, OAP40, contributes to the induction of interleukin-2 (IL-2), an early activation gene and major growth factor for T lymphocytes. Here we report that amino acid sequences obtained from purified OAP40 are identical to regions within JunD and c Jun. We demonstrate that each of these Jun family members can participate in a complex that includes Oct-1 and a regulatory element in the IL-2 enhancer. In transient transfections, both JunD and c-Jun can contribute to activation specific transcription mediated by this antigen receptor response element. These studies reveal a role, distinct from AP-1 activity, for Jun family members that is controlled by a calcium-triggered, cyclosporin A-sensitive mechanism. PMID- 8436292 TI - Rescue of the tail defect of Brachyury mice. AB - The mouse Brachyury (T) gene is required for normal development of axial structures. Embryos homozygous for the T mutation show severe deficiencies in mesoderm formation. They lack the notochord and allantois, have abnormal somites, and die at approximately 10 days postcoitum probably as a result of the allantois defect. Mice heterozygous for the T mutation exhibit a variable short-tailed phenotype. The T gene has been cloned and shown to be expressed in the tissues most strongly affected by the mutation. In this paper, we show that a single-copy transgene representing the wild-type T allele is able to rescue the T-associated tail phenotype. In addition, we show that increasing dosage of the T gene in Tc/+ mice causes an increased extension of the axis. These data show the correlation of the level of T product with the extension of the anteroposterior axis, directly demonstrating the involvement of the T product in this process. PMID- 8436293 TI - Transgenic mice as a model to study the role of TGF-beta-related molecules in hair follicles. AB - There is increasing evidence that members of the TGF-beta superfamily are important regulators of epithelial growth and differentiation in vivo. Here, transgenic mice have been used to study the role of the TGF-beta-related growth factors BMP-2 and BMP-4 in hair and whisker development. In the mature hair follicle, BMP-2 transcripts are normally seen only in precortex cells at the base of the hair shaft. In the transgenic mice reported here, BMP-4, a closely related molecule, has been ectopically expressed in the outer root sheath of hair and whisker follicles using an expression vector based on the bovine cytokeratin IV* promoter. In response to transgene expression, both outer root sheath cells below the stem cell compartment and hair matrix cells around the dermal papilla cease proliferation. In addition, the expression pattern of cytokeratin markers is disturbed in some transgenic hair follicles. These results support a model in which members of the TGF-beta superfamily play an active role in the inhibiton of cell proliferation and the onset of expression of trichocyte-specific genes that take place when cells leave the matrix of the follicle and differentiate into shaft cells. PMID- 8436294 TI - Molecular characterization of the her-1 gene suggests a direct role in cell signaling during Caenorhabditis elegans sex determination. AB - We have characterized two transcripts from the male-determining her-1 locus in Caenorhabditis elegans. The larger transcript, which appears more important for male development, is predicted to encode a novel 175-amino-acid, cysteine-rich polypeptide with an apparent amino-terminal signal sequence and potential cleavage and glycosylation sites. Expression of a full-length cDNA construct for the larger transcript driven by a body-wall-myosin promoter causes extensive masculinization of all sexually dimorphic tissues in XX (normally hermaphrodite) animals. This activity is dependent on the presence of the her-1 signal sequence or a substitute synthetic signal sequence in the encoded polypeptide. These results suggest that a secreted product of the her-1 gene dictates male development. PMID- 8436295 TI - Homology with Saccharomyces cerevisiae RNA14 suggests that phenotypic suppression in Drosophila melanogaster by suppressor of forked occurs at the level of RNA stability. AB - The suppressor of forked [su(f)] locus of Drosophila melanogaster encodes at least one cell-autonomous vital function. Mutations at su(f) can affect the expression of unlinked genes where retroviral-like transposable elements are inserted. Changes in phenotype are correlated with changes in mRNA profiles, indicating that su(f) affects the production and/or stability of mRNAs. We have cloned the su(f) gene by P-element transposon tagging. Alterations in the DNA map of eight lethal alleles were detected in a 4.3-kb region. P-element-mediated transformation using a fragment including this interval rescued all aspects of the su(f) mutant phenotype. The gene is transcribed to produce a major 2.6-kb RNA and minor RNAs of 1.3 and 2.9 kb, which are present throughout development, being most abundant in embryos, pupae, and adult females. The major predicted gene product is an 84- kD protein that is homologous to RNA14 of Saccharomyces cerevisiae, a vital gene where mutation affects mRNA stability. This suggests that phenotypic modification by su(f) occurs at the level of RNA stability. PMID- 8436296 TI - The extremely conserved amino terminus of RAD6 ubiquitin-conjugating enzyme is essential for amino-end rule-dependent protein degradation. AB - The RAD6 gene of Saccharomyces cerevisiae encodes a ubiquitin-conjugating enzyme that is required for DNA repair, damage-induced mutagenesis, and sporulation. In addition, RAD6 mediates the multiubiquitination and degradation of amino-end rule protein substrates. The structure and function of RAD6 have been remarkably conserved during eukaryotic evolution. Here, we examine the role of the extremely conserved amino terminus, which has remained almost invariant among RAD6 homologs from yeast to human. We show that RAD6 is concentrated in the nucleus and that the amino-terminal deletion mutation, rad6 delta 1-9, does not alter the location of the protein. The amino-terminal domain, however, is essential for the multiubiquitination and degradation of amino-end rule substrates. In the rad6 delta 1-9 mutant, beta-galactosidase proteins bearing destabilizing amino terminal residues become long lived, and purified rad6 delta 1-9 protein is ineffective in ubiquitin-protein ligase (E3)-dependent protein degradation in the proteolytic system derived from rabbit reticulocytes. The amino terminus is required for physical interaction of RAD6 with the yeast UBR1-encoded E3 enzyme, as the rad6 delta 1-9 protein is defective in this respect. The rad6 delta 1-9 mutant is defective in sporulation, shows reduced efficiency of DNA repair, but is proficient in UV mutagenesis. E3-dependent protein degradation by RAD6 could be essential for sporulation and could affect the efficiency of DNA repair. PMID- 8436297 TI - CAR2, a prestalk cAMP receptor required for normal tip formation and late development of Dictyostelium discoideum. AB - Extracellular cAMP serves as a primary signaling molecule to regulate the development of Dictyostelium discoideum. It is required for chemotaxis, aggregation, cytodifferentiation, and morphogenetic movement. The receptors for cAMP are members of the family of cell-surface receptors that are linked to G proteins and characterized by seven putative transmembrane domains. Previously, we have isolated the gene for the cAMP receptor subtype 1 (CAR1) from Dictyostelium and suggested that several genes related to CAR1 were present in the genome. Here, we describe a family of cAMP receptor genes of Dictyostelium and the isolation and function of the gene for the cAMP receptor subtype 2, CAR2. CAR2 is structurally similar to CAR1. Overall, their transmembrane and loop domains are approximately 75% identical in amino acid sequence; however, their carboxyl termini are quite dissimilar; CAR2 possesses homopolymeric runs of histidines and asparagines that are absent from the corresponding region in CAR1. Although CAR1 is maximally expressed during the early stages of development, CAR2 is expressed only after cells have aggregated and, then, preferentially in prestalk cells. Transgenic Dictyostelium that have had their wild-type CAR2 gene replaced by a defective copy using homologous recombination proceed through early development but are detained at the tight mound stage. CAR2 may be required for cAMP-directed sorting of prestalk cells during pattern formation within the aggregation mound. Furthermore, although prestalk genes are expressed normally in aggregates that lack CAR2, they exhibit an enhanced expression of prespore specific mRNA. Previously, we had shown that there was a requirement for CAR1 during early development. The present results demonstrate that the multiple responses of Dictyostelium to cAMP are regulated by distinct cAMP receptors that are encoded by unique genes. PMID- 8436298 TI - Integration of multiple developmental signals in Bacillus subtilis through the Spo0A transcription factor. AB - Multiple physiological and environmental signals are needed to initiate endospore formation in Bacillus subtilis. One key event controlling sporulation is activation of the Spo0A transcription factor. Spo0A is a member of a large family of conserved regulatory proteins whose activity is controlled by phosphorylation. We have isolated deletion mutations that remove part of the conserved amino terminus of Spo0A and make the transcription factor constitutively active, indicating that the amino terminus normally functions to keep the protein in an inactive state. Expression of an activated gene product is sufficient to activate expression of several sporulation genes in the absence of signals normally needed for initiation of sporulation. Our results indicate that nutritional, cell density, and cell-cycle signals are integrated through the phosphorylation pathway that controls activation of Spo0A. PMID- 8436299 TI - An everted repeat mediates retinoic acid induction of the gamma F-crystallin gene: evidence of a direct role for retinoids in lens development. AB - The vertebrate lens is a classical system for examining mechanisms of tissue determination and differentiation, yet little is known about the signaling molecules controlling its development. Here, we report that retinoic acid (RA), a substance known for its teratogenic effects on the eye and as a natural endogenous morphogenetic agent, acts as a regulator of gene expression in the lens. We have identified a novel type of RA response element (RARE) within the lens-specific mouse gamma F-crystallin promoter, consisting of two (A/G)GGTCA motifs in an everted arrangement spaced by 8 nucleotides. This element (gamma F RARE) mediates activation of the gamma F-crystallin promoter by ligand-activated endogenous lens cell RA receptors (RARs) and confers RA responsiveness when linked to a heterologous promoter. gamma F-RARE is bound in vitro by RAR/RXR heterodimers, and both receptors cooperate in vivo to trans-activate this element. These observations demonstrate a direct effect of RA on lens-specific gene expression and reveal a novel role for retinoids in the development and homeostasis of the mammalian eye. PMID- 8436300 TI - Stages in the second reaction of pre-mRNA splicing: the final step is ATP independent. AB - We have analyzed pre-mRNA splicing in yeast extracts immunodepleted of the PRP18 protein. We find that while the first step of splicing (cleavage at the 5' splice site, and generation of the exon 1 and lariat intermediates) is unaffected by the absence of PRP18, the second step of splicing (excision of the lariat intron and formation of mRNA) is substantially slower in the absence of PRP18. The splicing intermediates that are formed in the absence of PRP18 can be rapidly chased into products by the addition of purified PRP18 protein. This chasing is not dependent on ATP, implying that ATP is not required during the second cleavage-and-ligation reaction. This result suggests that there are ordered stages within the second step of splicing and that PRP18 acts late in the second step, perhaps during the catalytic step. The ATP independence also supports the idea that this reaction proceeds by a transesterification mechanism. PMID- 8436301 TI - [Olive oil dietary supplementation decreases susceptibility of LDL to oxidation and its uptake by macrophages]. AB - In atherogenesis, both peroxidation of low density lipoprotein (LDL) and accumulation of cholesterol in macrophages are involved. An oleic acid-rich diet was recently shown to reduce the susceptibility of rabbit and human LDL to in vitro oxidation. We therefore supplemented the diet of 10 normal men for 2 weeks with 50 g/d of olive oil, which is rich in oleic acid. This resulted in enrichment of their LDL with oleic acid (C18:1) and with sitosterol. After only 1 week LDL susceptibility to in vitro oxidation was significantly reduced, by 30% (p < 0.01). Macrophage uptake of LDL by the J-774A.1 macrophage-like cell line was reduced by 61%. We conclude that an olive oil-enriched diet possesses antiatherogenic properties, since it reduces the susceptibility of LDL to in vitro oxidation and inhibits uptake of LDL by macrophages. PMID- 8436302 TI - [Transfusion-related acute lung injury]. AB - Transfusion related acute lung injury develops a few hours after transfusion of blood products and is characterized by fever, chills, severe dyspnea and bilateral crepitations. Chest x-ray reveals diffuse patchy infiltrates and blood gas analysis shows severe hypoxemia. It is caused by an immunologic reaction of antileukocyte antibodies which, in most cases, are transfused with blood products. We present 2 patients with this syndrome who responded to large doses of corticosteroids (1 g methyl prednisolone) and made full recoveries within 96 hours. Medical personnel should be aware of this unique subtype of the adult respiratory distress syndrome, which responds to corticosteroids and has a favorable prognosis. PMID- 8436303 TI - [Acute lung injury as a complication of blood transfusion]. AB - Acute lung injury as a complication of blood transfusion (transfusion related acute lung injury) may occur a few hours following transfusion and is characterized by sudden respiratory distress, severe hypoxemia, fever and hypotension. The clinical picture develops rapidly and is severe, and the radiological findings mimic the adult type of respiratory distress syndrome (ARDS). Treatment is mainly supportive and includes corticosteroids. Despite the relatively good prognosis, fatalities have been described. The pathogenesis involves antileukocytic antibodies, usually of the donor but occasionally of the recipient. We describe a patient who developed such complication. Since blood transfusion is a routine procedure it is of utmost importance to draw the attention of physicians to this not uncommon and potentially fatal complication. Awareness will help to prevent it, and promote early diagnosis and treatment. PMID- 8436304 TI - [Pelvic inflammatory disease in pregnancy]. AB - Although pelvic inflammatory disease (PID) is a common complaint in young, fertile women, it is quite rare during pregnancy. Clinically it is characterized by abdominal pain, sometimes presenting as an acute abdomen with fever. Since PID has no characteristic clinical or laboratory findings, and is rare during pregnancy, it is understandable why the diagnosis is missed in most cases, and the patient is treated as an abdominal emergency. Since surgery during pregnancy in the presence of an infection leads to abortion in most cases, accurate diagnosis and appropriate treatment is of the greatest importance. A case of PID during pregnancy is presented. PMID- 8436305 TI - [Latex hypersensitivity in children]. AB - Latex (natural rubber), which is obtained from the Hevea brasiliensis tree, is known to cause contact urticaria and aggravate pre-existing atopic dermatitis. We present a 4.5 year-old boy with bladder exstrophy and epispadias who developed generalized urticaria and bronchospasm during general anesthesia prior to correction of the epispadias. He had undergone previous urologic operations uneventfully. Allergic evaluation revealed atopy with specific IgE antibodies against latex. Immediate skin tests performed with the medications given during the general anesthesia were negative, supporting the possibility that his anaphylactic reaction was caused by exposure to latex during intubation and ventilation. Similar cases have recently been described, especially in children with congenital urogenital abnormalities who are frequently exposed to latex (catheters, surgical gloves). Exposure to latex in these children should be minimized. In addition, they should be prepared with orally administered corticosteroids and antihistamine medication prior to operation. PMID- 8436306 TI - [Familial Mediterranean fever: from the clinical syndrome through the localization of the gene to the exploration of the biochemical anomaly]. PMID- 8436307 TI - [Shortage of organs for transplantation in Israel: have we given up?]. PMID- 8436308 TI - [Mammography screening for early detection of breast cancer: benefits vs risks]. PMID- 8436309 TI - [Quality of life after Roux-en-Y gastric bypass for morbid obesity]. PMID- 8436310 TI - [Hormonal treatment of advanced prostate cancer]. PMID- 8436311 TI - [Uveal malignant melanoma]. PMID- 8436312 TI - [Episodic angioedema with eosinophilia]. PMID- 8436313 TI - [Laparoscopic surgery: still in its infancy?]. PMID- 8436314 TI - [Endoscopic retrograde cholangiopancreatography combined with laparoscopic cholecystectomy]. AB - In 11 of 82 patients undergoing laparoscopic cholecystectomy, preoperative endoscopic retrograde cholangiopancreatography (ERCP) was performed. Indications were biliary pancreatitis in 5 and suspected common bile duct (CBD) stones in the other 6 (based on US or liver function tests, or both). The biliary tree was normal in 9 and laparoscopic cholecystectomy was performed. In 8 there was uneventful recovery but in the ninth open surgery was required when the attempted cholecystectomy resulted in uncontrolled cystic artery bleeding. Of the remaining 3 patients, 1 underwent sphincterotomy via ERCP and 3 weeks later, laparoscopic cholecystectomy. In the others, we intended to explore the CBD by laparoscopy, but had to resort to open cholecystectomy due to technical difficulties resulting from unsuspected acute cholecystitis. Based on our short experience, ERCP combined with laparoscopic cholecystectomy seems to be both safe and effective. PMID- 8436315 TI - [From "right to die" to "assisted death"]. PMID- 8436316 TI - [Arrhythmias following birth]. PMID- 8436317 TI - [Laparoscopic cholecystectomy]. PMID- 8436318 TI - [What are the patients' requests and expectations when they visit the doctor?]. PMID- 8436319 TI - [Falloposcopy--a new method for evaluation and treatment of infertility due to tubal factors]. AB - Tubal factors cause infertility in about a third of cases. With current diagnostic techniques, such as laparoscopy and hysterosalpingography, only a fraction of the causes of tubal infertility can be diagnosed and in many cases misdiagnosis results. Newer methods, such as ampullosalpingoscopy enable examination of the fimbria and ampullar segment of the fallopian tube, but the examination of the proximal tube, in which 10-20% of occlusions occur, is still impossible. We describe a new diagnostic technique, falloposcopy. It involves the transuterine insertion of a fiber optic device into the fallopian tube through a hysteroscope. This technique enables direct visualization of all segments of the fallopian tube, as well as removal of intratubal debris or adhesions. Using falloposcopy, a new grading method for tubal disease has been developed. We describe the results of 129 falloposcopic procedures in 82 women. Following falloposcopy, women with mild to moderate disease, according to the new classification, have conceived without further therapy during a follow-up period of up to 3 years. Falloposcopy may aid in differentiating between patients suitable for tubal surgery and those who should be referred for in vitro fertilization. PMID- 8436320 TI - [Malignant melanoma of the vulva]. PMID- 8436321 TI - [Medical care of the defenders during the siege of Tel-Hai]. PMID- 8436322 TI - [Calcium: recommended daily allowance, bone mass and preparations]. PMID- 8436324 TI - [Enuresis in children 5-18 years old in severe dysfunctional families]. AB - In a primary care setting 698 children aged 5-18 years were examined and 27 in 21 families were found to have enuresis nocturna. The control group included 127 children in 79 families who did not have enuresis. 13 (48.1%) children with enuresis, but only 8 (6.3%) control children, were from severe dysfunctional families. Such families are characterized by chronic and persistent conflicts, absence of closeness and lack of trust between parents and children, and lack of parental support (p < 0.001). Results were similar for boys and girls. The rate of parents with 8 or fewer years of education was significantly higher among children with enuresis as compared to controls, both with regard to fathers (p = 0.05) and mothers (p < 0.01). These findings indicate that severe dysfunctional families do not support maturation and personality development of their members. Early discovery of severe dysfunctional families promotes early intervention and effective treatment of enuresis in childhood. PMID- 8436323 TI - [Rubber-band ligation of esophageal and cardiac varices]. AB - Esophageal sclerotherapy was the treatment of choice for bleeding esophageal varices in the past decade. It is effective for treating acute variceal bleeding, as well as eradicating esophageal varices for secondary prevention of bleeding. However, in more than 20% of patients sclerotherapy involves complications, some of which are serious. The high complication rate suggested the development of a new method that should be at least as effective and as easy to perform as sclerotherapy, but with fewer complications and side-effects. Endoscopic variceal ligation was developed at the University of Colorado and described in 1986. It is reported to control active variceal bleeding in about 90% of patients, and to eradicate varices in about 80% of surviving patients. Complications are rare. We have adapted the method in our unit and here describe out preliminary experience in 11 patients. PMID- 8436325 TI - [Psychiatric manifestations in Wilson's disease]. AB - Wilson's disease is an inherited, autosomal recessive disease characterized by progressive hepatic and neurological symptoms. Clinical features usually start between the ages of 10 and 40. Psychiatric disturbances are present in almost all patients. In about a third of them psychiatric symptoms are present early in the disease and in almost 20% they precede hepatic and neurological dysfunction. In these cases the diagnosis of Wilson's disease is often difficult, as a result of which treatment is begun when the illness is already advanced. We report 3 patients with Wilson's disease in whom the psychiatric manifestations preceded neurological symptoms and necessitated admission for psychiatric treatment. PMID- 8436326 TI - [Rett syndrome]. AB - Rett syndrome was described relatively recently. It affects only females and is characterized by progressive deterioration of neurological status and impairment of psychomotor development. Psychomotor development is normal in the first year of life, but then there is deterioration of fine motor and language skills and later still, of gross motor skills. This results in severe motor function handicap and dementia. The arrested head growth, severe psychomotor retardation and typical "washing hands" movements are typical of Rett syndrome. We describe a 3-year-old Bedouin girl with the clinical picture of the syndrome and review the world literature, stressing the difficulty in detection and diagnosis. PMID- 8436327 TI - [Aneurysmal bone cyst of a lumbar vertebra in a child]. AB - An aneurysmal cyst of the 3rd lumbar vertebra was diagnosed in a 6-year-old girl. She presented with right loin pain and a palpable mass in the region of the second and third lumbar vertebrae. X-ray of the vertebrae, but not computerized tomography, was characteristic for the tumor. The diagnosis was confirmed by histologic examination. Aneurysmal cyst of the vertebra is rare in children. PMID- 8436329 TI - [Wheelchair adaptation]. PMID- 8436328 TI - [The search for bone marrow transplantation donors other than HLA-identical siblings]. PMID- 8436330 TI - ["Controlled" resuscitation for "uncontrolled" hemorrhagic shock]. PMID- 8436331 TI - [Ultrasonography--a major imaging tool in the diagnosis of intraocular tumors]. PMID- 8436332 TI - [Health and travel in the tropics]. AB - BACKGROUND: Roughly one-half of all travellers to the tropics become ill, either during or after their journey. MAJOR POINTS DISCUSSED: For counseling in the doctor's office, both the particular risks of the individual (pregnancy, childhood, chronic illnesses) and the specific situation in the country to be visited, duration of stay there, and the form of travels envisaged (hotel, trekking, safari, etc.), must all be taken into account. The major infectious diseases, their prophylaxis and their treatment are described. In addition to gastrointestinal infections, malaria today heads the list of health risks encountered in tropical countries. Of the almost 1000 cases of malaria reported every year in the FRG, about one-half contracts the feared quotidian (falciparum) malaria. In patients with relevant exposure, any flue-like illness must be suspected to be malaria until proved otherwise. Present-day possibilities of prophylaxis and treatment are presented. PMID- 8436333 TI - [Surgical therapy of frequent hand injuries. 1: Fractures and capsular ligament injuries]. AB - The hand is often involved in accidents and injuries. Most of these injuries can be treated adequately by the physician providing initial care. This paper gives the reader an outline of the most common hand injuries with the aim of facilitating recognition of the involvement of functional structures and thus ensure proper treatment or referral to the specialist. If a good functional results is to be achieved, misalignments in the longitudinal and transverse axes or torsional misalignments must be avoided. Fixation procedures facilitate provision of early-functional aftercare. In the event of injuries to the capsular ligament, a differentiation between complete and incomplete ruptures is of decisive importance for the further treatment. PMID- 8436334 TI - [Diagnosis in family practice. 2: Increased erythrocyte sedimentation rate]. PMID- 8436335 TI - [Syncope in Lown IVb ventricular arrhythmias and mitral valve prolapse]. AB - The indication for antiarrhythmic treatment in patients with the mitral valve prolapse syndrome is based mainly on symptomatology. In patients with a history of syncope in the presence of marked mitral valve reflux, recording of repetitive forms by means of Holter ECG and, when persistent ventricular salvos can be provoked by ventricular stimulation, long-term treatment with antiarrhythmic drugs should be considered. Especially in the case of troublesome palpitations resulting from ventricular extrasystoles, the substances of first choice are beta blockers. If these are not adequately effective, or if their use is contraindicated or not tolerated, class I and Ii antiarrhythmic drugs represent a therapeutic alternative. PMID- 8436336 TI - [How does the ovum become a fly? Gradients of a few proteins control the development of the Drosophila larva]. PMID- 8436337 TI - Molecular differential pathology of renal cell tumours. AB - Recent application of molecular cytogenetic techniques to the evaluation of renal cell tumours revealed four subtypes, each with a characteristic combination of genetic alterations within the chromosomal and mitochondrial DNA. The most common, nonpapillary renal cell carcinomas are characterized by the loss of chromosome 3p sequences, rearrangement of the chromosome 5q region and loss of the chromosome 14q sequences. Papillary renal cell tumours can be divided into two groups. Tumours with a combined trisomy of chromosomes 7 and 17 as well as loss of the Y chromosome are papillary renal cell adenomas. Tumours with additional trisomies such as trisomy 16, 20 or 12 are papillary renal cell carcinomas. Chromophobe renal cell carcinomas show a combination of allelic losses, which do not occur in other types of renal tumours. In addition, they have a rearrangement in the mitochondrial DNA. Renal oncocytomas are benign tumours marked by normal or abnormal karyotypes with balanced or unbalanced translocations and an altered restriction pattern of the mitochondrial DNA. Although the major cytological characteristics of renal cell tumours, such as clear, granular, chromophobe and oncocytic cell phenotypes correspond to nonpapillary, papillary and chromophobe renal cell carcinomas and renal oncocytomas, there are many cases with overlapping phenotype. Therefore, a classification of renal cell tumours based on specific genetic alterations is proposed. PMID- 8436338 TI - Stereological estimate of nuclear volume in endometrial adenocarcinoma of endometrioid type: reproducibility and intra-tumour variation. AB - Stereological volume weighted mean nuclear volume estimate (Vv) is reported to be highly reproducible and to provide excellent prognostic information for some tumours. The aim of the present study was to investigate the reproducibility and the intra-tumour variation of nuclear Vv and compare it with a morphometric nuclear estimate, i.e. the mean shortest nuclear axis, and with conventional histopathological parameters used in the grading of endometrial adenocarcinomas. Sixty-three endometrioid adenocarcinomas were included in the study. Both Vv and mean shortest nuclear axis showed an acceptable reproducibility and the correlation between them was moderate (Spearman test; rs = 0.8). One-third of the tumours showed a marked intra-tumour variation. A considerable discrepancy between Vv and/or mean shortest nuclear axis and nuclear and architectural grade was found. PMID- 8436339 TI - Intra- and inter-observer variation in the interpretation of histological features suggesting chromosomal abnormality in early abortion specimens. AB - Early spontaneous abortion is a common phenomenon, with more than 50% of early cases showing chromosomal abnormalities. We have undertaken a study to evaluate intra- and inter-observer reproducibility of histological diagnoses of features associated with chromosomal abnormalities, such as chorionic villus size, shape, vascularity, trophoblastic proliferation and trophoblastic pseudo-inclusions. The intra-observer variation for most histological features was small. However, the agreement beyond chance between two or more observers in judging histomorphological features of early abortion placentae only reached clinically relevant values for size and shape of the chorionic villi and for the number of trophoblastic pseudo-inclusions. PMID- 8436340 TI - Immunohistochemical detection of p53 and bcl-2 proteins in non-Hodgkin's lymphoma. AB - We have investigated the immunohistochemical expression of p53 protein in 96 cases of non-Hodgkin's lymphoma using a panel of five antibodies. Positive neoplastic cells were found in 30 (31.2%) cases, which could be divided into two groups according to their patterns of reactivity with the different antibodies; i.e. those positive with both polyclonal and monoclonal antibodies, and those which were stained only by monoclonal antibodies PAb1801 and/or PAb240. Positivity was nuclear in all but six cases in which cytoplasmic staining was found. In view of the hypothesis recently raised that p53 protein induces apoptosis we have compared our results with parallel staining for bcl-2 protein since bcl-2 is believed to be important, at least in lymphomas, in suppression of apoptosis. Staining for bcl-2 protein was performed on 83 cases and it was shown that p53-positive cases accounted for 10 out of 17 (59%) of the bcl-2-negative lymphomas but only for 15 out of the 66 (23%) bcl-2-positive cases, suggesting a possible relationship between the expression of these two proteins. Thus, our data show that p53 protein is abnormally expressed in a substantial proportion of non-Hodgkin's lymphomas and bears a significant inverse relationship to bcl-2 protein expression. However the molecular basis of this expression remains to be elucidated. PMID- 8436341 TI - p53 protein expression in non-neoplastic lesions and benign and malignant neoplasms of soft tissue. AB - Alterations of the p53 tumour suppressor gene, with consequent nuclear p53 protein accumulation, are among the most common genetic lesions in human neoplasms. In the present paper we show p53 immunoreactivity in 65% of malignant and 21% of intermediate malignancy soft tissue tumours, and in 48% of benign/reactive soft tissue lesions. p53 immunoreactivity of sarcomas can be interpreted as an indirect indication of a mutation of the corresponding p53 gene, suggesting that its alteration may have a role in their pathogenesis. Our data on p53 immunoreactivity in benign lesions of the soft tissues are among the first demonstrations of p53 over-expression in benign/reactive conditions. We cannot exclude mutations of the p53 gene in these cases, but it is difficult to sustain this hypothesis in reactive/pseudoneoplastic lesions. Alternatively p53 immunoreactivity in benign processes could be due to an increase in wild-type p53 as a result of different physiological mechanisms (cell type-specific p53 regulation, cell maturation, DNA repair). Our results do not indicate that immunohistochemical demonstration of p53 expression is a marker of malignancy in soft tissue tumours and therefore is of limited use in differential diagnosis. However, they suggest the need for further molecular genetic studies in order to elucidate the biological significance of the abnormal expression of p53 in benign soft tissue lesions. PMID- 8436342 TI - Mycobacterial cervical lymphadenitis in children: can histological assessment help differentiate infections caused by non-tuberculous mycobacteria from Mycobacterium tuberculosis? AB - Most mycobacterial lymphadenitis in children in developed countries is caused by non-tuberculous (the so-called 'atypical') mycobacteria. In view of the widely different treatment regimes and the requirement for contact tracing in Mycobacterium tuberculosis infections but not in non-tuberculous mycobacterial infections, it is very important to attempt to define histologically which is the aetiological agent. We have reviewed the histological appearances of mycobacterial cervical lymphadenitis in children and have found that, if any one of several 'atypical' features were seen, the appearances were much more likely to be due to a non-tuberculous mycobacterium. These features include ill-defined (non-palisading) granulomas, irregular or serpiginous granulomas, a predominantly non-specific granulomatous response, predominantly sarcoid-like granulomas or lack of significant caseation. In addition, the non-tuberculous mycobacterial infections showed a different distribution of neutrophil polymorphs, which tended to be seen in the centre of areas of necrosis rather than in Mycobacterium tuberculosis infections where a polymorph infiltrate, if present, was more diffusely scattered. Although no one definitive feature is diagnostic of non tuberculous mycobacterial infection, some features are helpful in differentiating the two groups of organisms histologically. PMID- 8436343 TI - Glomerular perfusion in renal allograft biopsies. AB - In the commonest causes of impaired renal transplant function there is reduced renal and glomerular perfusion. We investigated the possibility of identifying this phenomenon in renal transplant biopsies, by the crude but simple method of counting the mean numbers of glomerular capillary loops which contained erythrocytes. In cyclosporin toxicity, acute tubular necrosis and in acute cellular rejection there was a considerable reduction in the numbers of erythrocyte-containing glomerular capillaries. The separation of the acute tubular necrosis group from normal was almost complete. This feature is therefore not specific but appears to correlate well with states of impaired glomerular perfusion. We suggest that a simple assessment of glomerular erythrocyte 'load' forms a useful part of the histological examination of renal transplant biopsies. PMID- 8436344 TI - Legionnaire's disease mimicking pulmonary miliary tuberculosis in the immunocompromised. PMID- 8436345 TI - A bizarre parosteal osteochondromatous proliferation of the radius. PMID- 8436346 TI - Amiodarone-associated cirrhosis with hepatic and lymph node granulomas. PMID- 8436347 TI - Primary T-cell lymphoma of submandibular salivary gland. PMID- 8436348 TI - Ectopic parathyroid within a neck paraganglion. PMID- 8436349 TI - The impact of genetics on the classification of renal carcinoma. PMID- 8436350 TI - Pathology of the gastric antrum and body associated with Helicobacter pylori infection in non-ulcerous patients: is the bacterium a promoter of intestinal metaplasia? AB - A series of 115 consecutive, non-ulcerous, dyspeptic patients were examined for Helicobacter pylori (H. pylori) colonization in the gastric antral and/or body mucosa using Giemsa staining. Findings were correlated with the presence and degree of activity of superficial gastritis, deep gastritis, atrophic gastritis and with the presence of intestinal metaplasia. The prevalence of H. pylori positivity was 61.7%. In 59 of the 71 positive patients (83%), H. pylori was detected in the antrum or in both the antral and oxyntic mucosa. In the remaining 12 positive patients, H. pylori was detected only in the oxyntic mucosa nad in all these cases, the antrum showed intestinal metaplasia associated with atrophic gastritis (25%). In both antral and oxyntic mucosa, the activity of the gastritis was significantly correlated with H. pylori colonization. Linear logistic regression analysis showed that in patients with intestinal metaplasia the presence of H. pylori infection was significant in predicting the presence of more extensive intestinal metaplasia after adjusting for age. The prevalence of intestinal metaplasia types II and III was 65.5% in the H. pylori positive and 25% in the H. pylori negative patients. The antral mucosa is thought to be the elective site for H. pylori related histological lesions. At a later stage, H. pylori can be detected only in the oxyntic area while the antral mucosa shows extensive metaplastic or atrophic lesions. We would suggest that H. pylori plays a promotional role in the morphogenesis of intestinal metaplasia. PMID- 8436351 TI - Histology and immunohistochemistry of benign vaginal polyps and the normal vaginal subepithelial layer. PMID- 8436352 TI - Pagetoid infiltration in primary cutaneous melanoma. PMID- 8436353 TI - Expression of p53 in reactive mesothelium. PMID- 8436354 TI - Psychiatric nursing: coming of age at NIMH. PMID- 8436355 TI - Considering changes in adjustment disorder. PMID- 8436356 TI - Benefits of mobile crisis programs. PMID- 8436357 TI - Highlights of the 44th Institute on Hospital and Community Psychiatry. PMID- 8436358 TI - Providing assertive community treatment for severely mentally ill patients in a rural area. AB - OBJECTIVE: The authors' goals were to describe an assertive community treatment program developed for patients in rural South Carolina and to evaluate the effect of the program on rates of hospital utilization and cost of care. METHODS: Twenty three patients with chronic psychotic disorders living in rural areas of South Carolina were assigned to an assertive community treatment program. The patients' average number of days per year in the hospital, length of stay per admission, number of admissions per year, and estimated annual cost of care during the five years before assignment to the program and during a period from four to 26 months after assignment were compared. RESULTS: The intervention was associated with a 79 percent decrease in hospital days per year, a 64 percent decrease in the number of admissions per year, a 75 percent decrease in the average length of stay per admission, and a 52 percent reduction in estimated direct cost of care. CONCLUSIONS: Although the methods of assertive community treatment may need to be modified to suit the travel requirements and other characteristics of rural settings, the study results suggest that the model can be successfully used in rural areas. PMID- 8436359 TI - Inpatient treatment of schizophrenia in general hospitals. AB - OBJECTIVE: To improve treatment of schizophrenic patients in short-term inpatient units, the authors review studies of interventions that have been implemented with schizophrenic patients during brief hospitalizations and suggest areas for future research. METHODS: The review is organized around seven general treatment domains, including the therapeutic alliance, continuity of care, family involvement, procurement of community services, psychosocial rehabilitation, medication compliance, and substance abuse treatment. RESULTS AND CONCLUSIONS: Because schizophrenic patients have traditionally been treated in long-term settings, little literature exists to inform interventions on short-term units. The authors suggest that general hospital staff strengthen the treatment alliance between patients and outpatient clinicians, aggressively pursue community supports, work to ensure patients' follow-up with outpatient care, and consider depot medications and patient education to promote medication compliance. PMID- 8436361 TI - Consumerism and public psychiatry. PMID- 8436360 TI - Service utilization patterns as determinants of capitation rates. AB - OBJECTIVE: In a capitation payment system, the ability to project service requirements and cost is critical. The types and levels of services needed by persons with serious mental illness vary. The purpose of this study was to identify different patterns of service utilization and patient characteristics and costs associated with them. METHODS: Service use by 55 clients participating in a psychosocial-habilitation outpatient program at a hospital-based community mental health center was tracked for one year. Treatment cost for all services was calculated for each patient. RESULTS: Cluster analysis indicated that for persons with serious mental illness who enter community treatment, there appear to be four distinct patterns of service use: low, moderate, moderately high, and high. The groups were differentiated only by the presence of a disability (among the moderately high users) and a history of frequent inpatient treatment (among the high users). The two highest-use groups represented about one-third of the total sample but consumed more than three-fourths of the total resources. CONCLUSIONS: The lack of significant group differences on most clinical variables may make it difficult to develop capitation rates for subgroups of persons with serious mental illness. Service use may be determined by factors other than clinical need. PMID- 8436362 TI - Personality characteristics of men who physically abuse women. AB - OBJECTIVE: Studies have suggested that personality disorders may be common among men who habitually commit domestic violence. The study reported here attempted to characterize personality traits and psychological and cognitive characteristics of men who batter women in order to distinguish them from nonbattering men. METHODS: A group of 21 batterers were compared with a group of nonbatterers using the Minnesota Multiphasic Personality Inventory and its personality disorder scales (MMPIPDS) and the Hostility and Direction of Hostility Questionnaire. Comparability of the two groups was assessed on several demographic variables and on scores on the Revised Michigan Alcoholism Screening Test, three cognitive measures, and three measures of affective disturbance. RESULTS: Batterers scored higher on only the borderline and antisocial MMPIPDS and on the acting-out hostility and self-criticism scales of the hostility questionnaire. Problem solving skills for both of the groups were considerably poorer than published norms. No significant differences were found between the groups in age, race, education, socioeconomic status, alcohol abuse, performance on cognitive measures, depression scale scores, or overall scores on the MMPI. As children, batterers were more likely to have experienced physical or emotional abuse. CONCLUSIONS: Men who commit domestic violence may be found among a larger pool of men with poor problem-solving skills, but in addition they appear to have borderline-antisocial personality traits, certain types of hostility, and histories of abuse as children that may predispose them to become violent with their female companions. PMID- 8436363 TI - Psychotic symptoms in patients with borderline personality disorder and concurrent axis I disorder. AB - OBJECTIVE: Whether psychotic symptoms are part of the fundamental psychopathology of borderline personality disorder remains in dispute. The goal of the study was to examine the incidence and nature of psychotic symptoms in a sample of patients with the disorder. METHODS: The inpatient psychiatric records of 92 patients with a discharge diagnosis of borderline personality disorder, some of whom had comorbid affective disorder or substance abuse disorder, were examined to obtain data on the presence of psychotic symptoms (narrowly defined as delusions and auditory and visual hallucinations), the duration of psychotic episodes, and the clinical characteristics of the patients. RESULTS: Twenty-seven percent of the patients had psychotic episodes, typically lasting many weeks. Comorbid affective or substance abuse disorders did not predict psychotic symptoms. CONCLUSIONS: Psychotic episodes are common but not universal among patients with borderline personality disorder, regardless of whether a concurrent axis I disorder is present. Those episodes are not necessarily brief or transient, and borderline patients who experience psychotic episodes are likely to have repeated hospitalizations. PMID- 8436364 TI - Characteristics of youths identified from a psychiatric case register as first time users of services. AB - OBJECTIVE: The study examined associations between sociodemographic factors and first-time use of mental health services by children and adolescents, including whether the patterns differ by age at first treatment contact. METHODS: The authors examined sociodemographic characteristics of 4,949 youths listed on a psychiatric case register in Monroe County, New York, who were under age 19 when first seen for public mental health treatment between 1987 and 1989. Data on race and type of insurance for patients in the county's four catchment areas were compared with 1980 census data. Insurance was categorized as public (such as Medicaid) or private and was used as a proxy for socioeconomic status. RESULTS: Both minority and publicly insured youths of low socio-economic status were overrepresented in the treatment population in relation to their numbers in the county, although publicly insured youths from the poorest catchment area were underrepresented in the treatment population. Among children (ages five to 12) in the treatment population, males outnumbered females by 2 to 1, but among adolescents (ages 13 to 18), the numbers were similar. Among minority groups, children receiving first-time mental health services were more likely to have public insurance. Minority adolescents were somewhat more likely to be privately than publicly insured. PMID- 8436365 TI - A model of inpatient child and adolescent care using a consulting psychiatrist. AB - Since 1976 a child and adolescent unit in a public psychiatric hospital has used a part-time child and adolescent psychiatrist to improve inpatient treatment. In this model the consultant is directly responsible for all admission and discharge decisions. The consultant provides only essential medical treatment, which includes assessing, monitoring, and evaluating patients and prescribing medications, and directs patient care through nonmedical primary clinicians. A senior nurse coordinates on-site scheduling, confirms orders, documents treatment changes, and routinely phones the consultant with clinical updates. The consultant enhances the skills and performance of hospital staff and local physicians through case consultation and other interchanges. The authors recommend the model for the public sector because it increases the possibility of recruiting private-sector psychiatrists into the public system. PMID- 8436366 TI - Brief treatment of anorexia nervosa in military personnel. PMID- 8436367 TI - Effects of hospitalization on use of outpatient medical and psychiatric services. PMID- 8436368 TI - Elements of a psychosocial clubhouse program associated with a satisfying quality of life. PMID- 8436369 TI - Assessment by telemedicine. PMID- 8436370 TI - Lithium toxicity. PMID- 8436371 TI - NIMH report tracks trends in growth of partial care services; 488,000 episodes treated in 1988. PMID- 8436372 TI - Foucha v. Louisiana: when must the state release insanity acquittees? PMID- 8436373 TI - Champions of change. Today's CFOs learn to say 'yes' to TQM, patient-centered care and critical paths. AB - Still clinging to that old image of the hospital CFO as the person with the green eye shades and columnar paper who always says 'no'? Forget it. Today's CFO is a coach, teacher, leader and strategist. The new CFO is also a facilitator, actively finding ways to promote change, and actively finding ways to say "yes". At the root of this change is the CFO's involvement in initiatives--particularly TQM/CQI, patient-centered care and critical paths programs--that require a completely new approach to internal financing. In the process, inter-departmental relations at those hospitals are changing dramatically as well. PMID- 8436374 TI - Transition to a new future. An expert lays out strategies for a redesigned system. AB - Making the shift from today's fragmented health care system to the post-reform system of the future will require a shift in thinking and planning. As the author explains, transitional planning provides a new model for health care executives, one based on the assumption of collaboration rather than competition, and one that anticipates the very different demands of the future. PMID- 8436375 TI - Joining forces. Maine hospitals find that cooperation brings results. AB - Examples of collaboration among hospitals are becoming the norm and not the exception in Maine, where a recently enacted law is encouraging cooperation. In fact, 21 hospitals in that state belong to a statewide group that meets monthly to develop collaborative solutions to community health concerns in a cost effective and quality-oriented fashion. PMID- 8436376 TI - Medicaid worries. States dispute rule on new funding limits. AB - The Clinton administration last month indicated that it will be sympathetic to how states will fare under federal limits on disproportionate-share hospital payments and provider taxes. But while states and providers knew what was in store for them under a federal statute, many say that the Health Care Financing Administration's initial interpretation goes too far and would sabotage funding systems they designed around the law. PMID- 8436377 TI - American Hospital Association. 1993 Directory. PMID- 8436378 TI - Clinton's health care task force takes shape. PMID- 8436379 TI - Regional waste pact has layers of dividends. PMID- 8436380 TI - 1992 receivables improved, but cash flow was weak. PMID- 8436381 TI - Data watch. Hospitals prepare for ambulatory care growth. PMID- 8436382 TI - Health care's new frontier: challenges abound. PMID- 8436383 TI - Human genome diversity initiative. PMID- 8436385 TI - Isolation by distance, trend surface analysis, and spatial autocorrelation. AB - The isolation by distance model is both a population process and a surface model. In this model the surface is, on average, flat in every direction. By contrast, probably most observed genetic surfaces exhibit trends generated by complex long distance populational processes. When one estimates the parameters of a Malecot Morton equation for those surfaces, the isolation by distance model does not fit. In the simplest case, in first-order trends (two-dimensional clines) the genetic differentiation increases dramatically, faster per unit distance than it would by isolation by distance alone. When isolation by distance takes place but is hidden through the apparent and complicated relief of a surface, another surface model incorporating trend spatial analysis can bypass the difficulty of estimating the isolation by distance process if approached through the Malecot-Morton equation or through a measure of spatial autocorrelation. PMID- 8436384 TI - Geographic spread of measles on the island of Dominica, West Indies. AB - Because of the short incubation period of most acute infectious diseases, short term and daily mobility are more important than permanent and seasonal migration for the spread of these diseases. Yet most studies of population mobility focus on permanent or semipermanent change of residence. Here, we describe the results from a field study conducted on the island of Dominica, West Indies, during the summers of 1989 and 1990 and the winter of 1991. The study was designed to collect data on short-term mobility rather than migration. These mobility data are linked with data on the patterns of measles transmission during a 1984 epidemic. Three-hundred five individuals from all parts of the island were interviewed about their daily travel patterns, their travel off the island, and the travel of members of their immediate family. In addition to these respondents, interviews were conducted with representatives of most of the major occupations that involve travel in the course of a workday. Data were also collected on the number and type of motor vehicles traveling along various routes on the island and on travel of native residents to the capital city, Roseau, to buy or sell at the major weekly market. Analysis of the interviews shows that travel within the island is clearly nonrandom. For example, almost everyone interviewed traveled to Roseau at least once a month, but 40% of the respondents had never been to any of the major villages in the Grand Bay Health District, which is only about a half-hour from Roseau. Patterns of disease transmission have been directly affected by these mobility patterns. The measles epidemic in 1984 apparently did not reach the Grand Bay Health District, even though all other areas of the island experienced significant rates of infection. Analysis of reasons for the relative isolation of the Grand Bay Health District indicates the importance of transportation patterns, as well as social, cultural, and geographic factors, to the disease transmission patterns throughout the island. PMID- 8436386 TI - Palatal and alveolar arch dimensions in 47,XXY (Klinefelter syndrome) men. AB - Men with one extra X chromosome (47,XXY; Klinefelter syndrome) show a tendency to have a shallower but longer palate than normal (46,XY) men. The palate is also narrower than in 46,XY men. The mandible is clearly narrower but sagittally longer compared with the mandibles of 46,XY men. The present results indicate that the presence of one extra X chromosome in 47,XXY men is reflected in decreased growth of the maxilla transversely and vertically and of the mandible transversely. Increased length of the alveolar arches might be partly a compensation for the decreased width of the alveolar arch. This change might be associated with larger tooth sizes in 47,XXY men. Unbalanced appositional growth rather than disturbances in other orofacial growth mechanisms might be associated with the XXY sex chromosome pattern. PMID- 8436387 TI - Metric characters of the hard palate and their cephalometric correlations in Namibian !Kung San and Kenyan tribes. AB - The metric characters of the head and hard palate of 138 black males from Kenya and 110 male !Kung San from Namibia have for the first time been compared to describe the black and Khoisan variation with respect to these special trait systems. The palate measurements were taken from prints of self-hardening plastic. Nearly all metric characters show significant differences between the two populations, which are reflected in a relevant discriminant function. The analyses of correlations between the individual head and palate measurements yield different correlation patterns in the two samples also with regard to their significance and direction. These results and the generally low correlation coefficients can be explained by the complex processes of allometric head growth, resulting in the Sans' pedomorphous and the blacks' more adultiform head and palate trait combinations. PMID- 8436388 TI - Genealogy and regional distribution of lipoprotein lipase deficiency in French Canadians of Quebec. AB - Lipoprotein lipase (LPL) deficiency, an autosomal recessive disorder causing chylomicronemia, has a high prevalence in the French-Canadian population of Quebec. The molecular basis of LPL deficiency has been defined, and two major mutations have been shown to have an uneven geographic distribution. Two mutations, one at residue 188 (M-188) and the other at residue 207 (M-207), are described here; they account for 95% of the mutant alleles. The carrier rate of M 188 was highest in western Quebec (1/326) but that of M-207 was much higher in the eastern part of the province (1/85). Genealogical reconstruction has revealed that both mutations were introduced to the French-Canadian population by migrants from France in the seventeenth century. M-188 is likely to have a Scottish ancestor, whereas M-207 appears to be of French origin. PMID- 8436389 TI - Molecular characterization of glucose-6-phosphate dehydrogenase variants from Brazil. AB - Electrophoretic surveys of 7794 individuals from different regions of Brazil and a study of subjects with hemolytic anemia have disclosed 9 putative G6PD variants in addition to the B, A, A-, and Mediterranean types. No variants were found among the 3739 Brazilian Indians tested. Four variants underwent DNA analysis. Three were identified with the Mediterranean, Seattle, and Anaheim types, but the fourth variant was previously undescribed and we propose to designate it G6PD Sao Borja. PMID- 8436390 TI - Hematocrit levels in children at sea level and at high altitude: effect of adrenal androgens. AB - Hematocrit values are normally higher in natives living at high altitude than in natives living at sea level. Here, we have determined the hematocrit levels in relation to adrenal androgens in children living at altitudes of 150 m and 3400 m above sea level. The data demonstrate no association between serum adrenal androgens levels and hematocrit values. For all ages studied, hematocrit levels were higher in children at high altitude than in children at low altitude. Higher hematocrit values (> or = 54%) were observed in 15% of native boys at 3400 m. These data suggest that the higher hematocrit levels observed normally in children at high altitude are mainly related to altitude hypoxia and not to adrenal androgens. PMID- 8436391 TI - Estimation of fecundity and secondary sterility from survey data on birth intervals in Egypt. AB - Data on the last closed and open birth intervals have been used to ascertain the current potential of childbearing for women in terms of estimating fecundity and secondary sterility by age, residence, and educational subgroup. Under the assumption that after a specific period from the last birth a certain proportion of women become secondarily sterile, we propose and apply an inflated model of open birth interval to obtain the proportion of women who are secondarily sterile. The data used for the analysis are extracted from the Egyptian Fertility Survey conducted in 1980. PMID- 8436392 TI - Global survey of human genetic diversity: a focal point for human biology. PMID- 8436393 TI - Effects of breast feeding after resumption of menstruation on waiting time to next conception. AB - We investigate the association between breast feeding after resumption of menstruation and the duration from resumption of menses to the next conception. Data from a survey, "Breast-Feeding and Its Effect on Fertility," conducted in 1987 under the auspices of the Centre of Population Studies, Banaras Hindu University, India, were used. We used hazard models of conception rates after the return of menstruation with breast-feeding duration as a time-dependent covariate. The interaction of breast-feeding duration after resumption of menses and postpartum amenorrhea have a significant effect on the rate of conception after return of menses. After resumption of menstruation, when there is no breast feeding, the risk of conception increases with the increase in postpartum amenorrhea. However, breast feeding attenuates the effects of postpartum amenorrhea. These results suggest that breast feeding beyond the resumption of menstruation plays a significant role in the proximate determinants to reduce fertility. PMID- 8436394 TI - Grief intensity following the loss of a twin and other relatives: test of kinship genetic hypotheses. AB - Following Darwin, we summarize evidence that grief may be an evolved adaptive mechanism with complex physiological and psychological correlates. Given this state of affairs, kinship genetic theory suggests that in humans ratings of grief intensity should increase with increasing genetic relatedness to the deceased. A study of the bereavement experiences of 49 surviving monozygotic (MZ) and 19 surviving dizygotic (DZ) co-twins provides informative tests of this hypothesis. Participants completed a comprehensive Twin Loss Survey, which was designed to assess intensity of bereavement in response to the death of the twin and other relatives. The mean grief intensity rating for the deceased twin was significantly higher for surviving MZ twins than for surviving DZ twins (p < 0.01). Mean grief intensity ratings for twins significantly exceeded those for mothers (p < 0.05), fathers, grandfathers, grandmothers, and other relatives (p < 0.01). These findings are consistent with kinship genetic predictions. PMID- 8436395 TI - Mechanism of lymphocyte-mediated cytolysis: functional cytolytic T cells lacking perforin and granzymes. AB - Involvement of the lytic protein perforin (c. 65,000 MW) and of granule proteases (granzymes) in cell lysis induced by cytolytic T lymphocytes (CTL) has been suggested, but is still controversial. For example, in vivo-primed peritoneal exudate CTL (PEL) have been found to express perforin and granzyme activity in amounts comparable to those found in non-lytic lymphocytes, although PEL are the most potent of all CTL. Exploiting several cloned CTL hybridomas developed in this laboratory and newly available molecular probes for detecting perforin, granzymes, protein and mRNA, we now directly demonstrate killer T lymphocytes which kill effectively and specifically, but are free from perforin, lytic granules and granzymes, all three of which have been postulated to be involved in lymphocyte-mediated killing. The CTL hybridomas are completely devoid of perforin and granzymes prior to, during, and after activation by antigen, mitogen or interleukin-2 (IL-2). The induction of lytic granules, perforin, and granzymes in the in vivo-primed PEL, but not in the cloned CTL hybridomas, upon cultivation in IL-2, further suggests the involvement of these constituents in antigen/lymphokine-induced CTL activation and differentiation rather than directly in their cytocidal activity. Together, these findings support a perforin and granzyme-independent CTL lytic mechanism. PMID- 8436396 TI - Direct evidence for clonal destruction of allo-reactive T cells in the mice treated with cyclophosphamide after allo-priming. AB - It has previously been reported that a single i.p. injection of 200 mg/kg cyclophosphamide (CP) 2 days after priming with 10(8) donor spleen cells (SC) leads to donor-specific skin allograft tolerance in H-2 compatible, multiminor antigen incompatible murine strain combinations. It is speculated that the i.v. injection of donor cells may result in synchronized proliferation of donor reactive host T cells and subsequently administered CP may specifically destroy these proliferating T cells in the periphery. Although this unique action of CP is considered to be a principal mechanism in this method, direct evidence has not yet been obtained. In the present article, this in vivo destructive effect of CP is clearly demonstrated by assessing detailed kinetics of host-derived blastoid T cells and donor (Mls-1a)-reactive V beta 6+ T cells in the model system of C3H mice rendered tolerant to AKR. Frequencies of the blastoid cells and V beta 6+ cells, which increased as a result of AKR priming, decreased rapidly with the administration of CP. C3H mice, which received AKR SC alone, also exhibited partial deletion of V beta 6+ T cells, but both tempo and magnitude of decrease in the frequency of V beta 6+ cells were quite different from those of the C3H mice given AKR SC and CP, which showed more rapid and profound elimination of V beta 6+ T cells. In accordance with these kinetic studies, in vitro proliferative response to Mls-1a antigens was greatly impaired in mice treated with SC and CP, whereas a low but appreciable response was detected in mice given SC alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8436397 TI - Anti-T-cell receptor V beta 6 breaks tolerance in Mlsa mice and induces production of anti-Mlsa antibodies. AB - Tolerance to the minor lymphocyte stimulating (Mls) self-antigens has been shown to be due to the intrathymic deletion of T-cell clones bearing certain T-cell receptor (TcR) V beta regions. T cells bearing these V beta regions (V beta 6, V beta 7, V beta 8.1, V beta 9) are deleted in Mlsa-positive mice. This report demonstrates that hyperimmunization of AKR mice with anti-V beta 6 breaks tolerance to the self-antigen Mlsa and induces the development of anti-Mlsa antibodies. These antibodies had the capacity to block Mlsa-induced mixed lymphocyte responses between H-2 identical strain combinations and also between Mlsa-congeneic BALB.D2MA and parental BALB/c strains. Furthermore, when the responder lymphocytes were Mlsa-positive their response to allogeneic major or minor histocompatibility antigens was enhanced in the presence of this antiserum. This indicates that Mlsa may be present on T cells and that occupancy of this ligand leads to enhanced signal transduction. PMID- 8436398 TI - Interleukin-2- and interferon-gamma-secreting T cells in normal and diseased human intestinal mucosa. AB - A sensitive reverse haemolytic plaque assay to detect lymphokine-secreting T cells, and Northern blot analysis to detect expression of lymphokine messenger RNA (mRNA) were used to study interferon-gamma (IFN-gamma) and interleukin-2 (IL 2) production in the mucosa of children with Crohn's disease or ulcerative colitis (UC), and in histologically normal mucosa from patients without inflammatory bowel disease. In the mucosa of most patients with UC and control patients, IL-2- and IFN-gamma-secreting cells were absent or were present at only low levels. In contrast, in mucosa from patients with Crohn's disease, lymphokine secreting cells were readily detectable (3-18%). IFN-gamma mRNA was detected by Northern blot analysis in 5/6 Crohn's tissues, but only in 1/5 UC samples and none of nine samples of control mucosa. These studies reveal an ongoing cell mediated immune response in the mucosa in Crohn's disease. PMID- 8436399 TI - Dendritic cells, the major antigen-presenting cells of the human colonic lamina propria. AB - Induction of T-cell responses requires the recognition of antigen in association with class II major histocompatibility complex (MHC) antigens on specialized antigen-presenting cells. It was previously demonstrated that dendritic cells were the major antigen-presenting cell in the mouse intestinal lamina propria whilst macrophages were shown to be suppressive. The aim of this study was to compare the antigen-presenting cell activity of human colonic dendritic cells with macrophages. Colonic mucosa was removed from 46 specimens resected for cancer and other non-malignant conditions and lamina propria cell suspensions obtained by EDTA treatment followed by enzymatic digestion. Lamina propria cell suspensions, depleted of macrophages by adherence to insolubilized human immunoglobulin and carbonyl iron phagocytosis, were enriched for dendritic cells by density gradient centrifugation. Yields represented 0.9% (range 0.7-1.4%) of the starting cell number and the degree of enrichment was 30-50%. Immunocytochemistry demonstrated high levels of class II MHC antigen expression, but low levels or absent expression of macrophage and other markers. The ultrastructural features of the low-density cell fraction were typical of dendritic cells with cytoplasmic extensions or veils and the absence of phagocytic vesicles. Populations of cells enriched for macrophages were obtained by harvesting the human immunoglobulin-adherent cells. These cells were > 70% positive for macrophage markers using immunocytochemistry. The ability of lamina propria cells to induce primary T-cell activation was assayed using allogeneic peripheral blood T cells as responders in the mixed leucocyte reaction (MLR). When antigen-presenting activity was assessed using the MLR, the stimulatory activity was present in the dendritic cell-enriched fraction, with little activity present in the macrophage fraction. These data indicate that dendritic cells, not macrophages, are the major cell population capable of generating a mixed leucocyte reaction in the human colonic lamina propria. PMID- 8436400 TI - Increased proliferative response of lymphocytes from intestinal lymph during long chain fatty acid absorption. AB - The effect of long chain and medium chain fatty acid absorption on transport and mitogen-induced blast transformation of lymphocytes in intestinal lymphatics was investigated. Intestinal lymph was collected from mesenteric lymph duct cannulated rats maintained in Bollman's cage. Following the intraduodenal administration of oleic acid (long chain fatty acid) or octanoic acid (medium chain fatty acid), only oleic acid produced a significant increase in lymphocyte flux and enhanced proliferative response of lymphocyte in intestinal lymph, without significant alteration of lymphocyte subsets. These changes appeared to be closely correlated with the appearance of radiolabelled oleic acid. Absorption of a medium chain fatty acid, octanoic acid, most of which appeared to be transported to portal blood, did not produce a significant elevation of lymphocyte flux or increased proliferative response of lymphocyte in intestinal lymph. Pluronic L-81, which is a potent inhibitor of the intracellular formation and secretion of chylomicron, significantly attenuated the increased lymphocyte flux and suppressed the enhancement of lymphocyte responsiveness to PHA in intestinal lymph after stimulation by oleic acid administration. There is a possibility that lymphocyte transport and proliferative response in intestinal lymph during oleic acid absorption are closely related to the process of chylomicron formation and secretion to lymphatics in the intestinal mucosa. PMID- 8436401 TI - Decrease in susceptibility to oral tolerance induction and occurrence of oral immunization to ovalbumin in 20-38-week-old mice. The effect of interval between oral exposures and rate of antigen intake in the oral immunization. AB - Maturation into adulthood, from 8 to 24 weeks of age, significantly influences the induction of oral tolerance in different strains of mice. Animals from strains which are susceptible to the induction of oral tolerance to ovalbumin (OVA) at 8 weeks of age become refractory at 24 weeks of age. Furthermore, in several strains, intermittent exposure to OVA exclusively by gavage resulted in high titres of circulating anti-OVA antibodies. However, the voluntary intake of similar doses of OVA at the same intervals failed to immunize mice of one of the most responsive strains, H-III. PMID- 8436402 TI - Structural similarity between bovine conglutinin and bovine lung surfactant protein D and demonstration of liver as a site of synthesis of conglutinin. AB - Conglutinin is a Ca(2+)-dependent, carbohydrate-binding, serum protein which contains an N-terminal collagen-like region and a C-terminal, C-type lectin domain. To date, conglutinin, which appears to play an important role in defence mechanisms, has been fully described, by protein sequence analysis, only in the bovine system. To allow comparison of lung surfactant protein D (SP-D) with conglutinin, within one species, a full-length cDNA clone for SP-D has been isolated from a bovine lung library. The derived amino acid sequence for bovine SP-D shows a higher (78%) level of identity to the sequence of conglutinin than to the sequence of human or rat SP-D (67 and 65% respectively). However, SP-D and conglutinin are known to have different carbohydrate-binding specificities, therefore some of the 16 residues conserved in the C-type lectin domains of all three species of SP-D, but which are not conserved in conglutinin, appear likely to be involved in determination of specificity. The use of a polymerase chain reaction (PCR)-derived DNA probe for bovine SP-D in Northern blotting studies yielded a signal from bovine liver mRNA as well as the expected signal from bovine lung mRNA. Since SP-D appears to be a lung-specific protein, it seems probable that the liver is the primary site of synthesis of conglutinin. PMID- 8436403 TI - Cytotoxic activity of human lymphocytes against differentiated intestinal tumour cell lines. AB - The natural killer (NK) and lymphokine-activated killer (LAK) cytotoxic activity of human peripheral blood lymphocytes (PBL) against various human tumour cell lines from intestinal origin (WIDR, HT29, Caco-2) has been investigated. The differentiated Caco-2 cells were then used as a model to investigate the cytotoxic activity against enterocyte-like target cells. Caco-2 were seeded on polycarbonate filters and maintained in culture for at least 15 days to allow the differentiation and formation of tight junctions. The integrity of tight junctions was assayed by measuring [3H]mannitol flux from apical to basolateral compartment. Cytotoxic analysis showed that both differentiated and undifferentiated Caco-2 cells were similarly susceptible to NK and LAK activity. The capacity of cytotoxic lymphocytes to kill enterocyte-like cells with intact junctional complex may suggest a direct role of cytotoxic lymphocytes in causing intestinal lesions under inflammatory conditions. PMID- 8436404 TI - Comparison of antigen presentation by lymph node cells from protein and peptide primed mice. AB - Lymph node cells from mice primed with peptides from the allergens Der p I and Der p II (the group I and II allergens of Dermatophagoides pteronyssinus) were unable to recall responses to the protein antigen when cultured in vitro despite being able to mount large responses to the peptides. The T cells could however recall responses to the protein when spleen-adherent cells were added into culture. Treating the spleen accessory cells with the monoclonal antibody (mAb) 33D1 and complement largely abrogated the protein response of peptide-primed T cells which indicates that dendritic cells were mainly responsible for the antigen-presenting function. If mice were primed with two injections of peptide the lymph node cells obtained could respond to both protein and peptides in vitro without the need for exogenous accessory cells. Using either negative depletion with the J11D mAb or positive purification, it was found that the presentation of protein antigen to lymph node T cells primed with either protein or peptide was limited to antigen-specific B cells. Peptide antigens could however be presented by both B and non-B populations. In one case the peptide 105-129 from Der p II which contains a T-cell epitope could not be shown to induce T-cell responses in the lymph node unless presentation was mediated by spleen-adherent or B-specific cells. These results are important for peptide-based immunomodulation and in interpreting results obtained from lymph node cultures. PMID- 8436405 TI - Specific cleavage of the alpha 4 integrin associated with activation of peripheral T lymphocytes. AB - The heterodimeric VLA-4 integrin has been implicated in lymphocyte migration to inflamed peripheral tissues, lympho-haemopoiesis and autoimmune disease. To determine the structure and function of VLA-4 in physiological processes, molecular forms of the VLA-4 alpha-chain were analysed during T-cell activation. The results showed that prolonged activation of human peripheral T cells was associated with increased cleavage of the 150,000 MW alpha 4 chain into 80,000 and 66,000 MW fragments. Similar-sized alpha 4 fragments could also be generated from 150,000 MW alpha 4 on intact resting T cells by brief trypsinization, whereas trypsin treatment of isolated 150,000 MW alpha 4 resulted in nearly complete protein degradation. Native 80,000 and 66,000 MW alpha 4 chains on activated T cells could not be digested further by trypsin. These results indicated that specific cleavage of 150,000 MW alpha 4 was largely dependent on the tertiary structure of native alpha 4 chains. To determine the specific cleavage site in alpha 4 on peripheral T cells, VLA-4 was isolated and purified from in vitro-activated T cells and the N-terminus of the 66,000 MW fragment was partially sequenced. The sequence SKR/STE was identified as the specific alpha 4 cleavage site on T cells. These results indicate that T cells, upon activation, acquire an enhanced dipeptidase processing activity, which cleaves alpha 4 at a specific site. PMID- 8436406 TI - Activation of extrathymic T cells in the liver during liver regeneration following partial hepatectomy. AB - Partial hepatectomy was performed in C57BL/6 mice to investigate whether extrathymic T cells in the liver are activated during liver regeneration. This study is based on the finding that in mice with malignant tumours, extrathymic T cells in the liver are activated and yet the intrathymic pathway is suppressed (i.e. thymic atrophy). Attention was therefore focused on whether a similar phenomenon is induced during benign cell regeneration. Extrathymic T cells were identified using the two-colour immunofluorescence test for CD3 and interleukin-2 receptor beta-chain (IL-2R beta) [or lymphocyte function-associated antigen-1 (LFA-1)] antigens. They were estimated to be intermediate CD3+ [or T-cell receptor (TcR)] cells with high expressions of IL-2R beta and LFA-1. It was demonstrated that the proportion and number of intermediate CD3+ cells increased in the early phase (days 2-4 after partial hepatectomy), and that the thymus was inversely atrophic at the same time. This raised the possibility that extrathymic T cells may also be responsible for regulation of normal cell regeneration. PMID- 8436407 TI - Locomotor responses of human CD45 lymphocyte subsets: preferential locomotion of CD45RO+ lymphocytes in response to attractants and mitogens. AB - The CD45RO+ population of lymphocytes from human blood contains a higher proportion of locomotor cells than the CD45RA+ population. Direct from blood there were few locomotor lymphocytes (< 15%), but, among these, a higher proportion of CD45RO+ than of CD45RA+ cells responded to the chemotactic stimuli, foetal calf serum (FCS) and interleukin-2 (IL-2) in polarization assays. Likewise, after overnight culture, a higher proportion of CD45RO+ cells responded to IL-8. Culture for 24-72 hr in activators such as anti-CD3, purified protein derivative (PPD), phytohaemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM) or in an allogeneic mixed leucocyte reaction (AMLR) increased the proportion of locomotor lymphocytes to 20-60%, and the CD45RO+ subset showed proportionately more polarized cells than the CD45RA+ subset after culture with all the above activators. Preferential migration of CD45RO+ cells into collagen gels was also seen after culture in antigenic stimuli (PPD or AMLR) but not with polyclonal activators (alpha CD3 or Con A). Double labelling showed that, within the CD4+ and CD8+ subsets, antigen-stimulated CD45RO+ T cells invaded collagen gels in higher proportions than CD45RA+ T cells. Clustering of lymphocytes with accessory cells is an essential prerequisite for locomotion and, after culture in alpha CD3, CD45RO+ lymphocytes were found preferentially in clusters with monocytes. In all of the above populations, CD45RO+ lymphocytes were larger in size. These findings suggest that, not only selective adhesion to vascular endothelium as reported earlier, but also selective locomotion recruits CD45RO+ lymphocytes into sites of inflammation. PMID- 8436408 TI - Carnosine (beta-alanylhistidine) protects from the suppression of contact hypersensitivity by ultraviolet B (280-320 nm) radiation or by cis urocanic acid. AB - Carnosine is a naturally occurring histidine-containing dipeptide in mammalian tissues for which a physiological role has not been defined. It has antioxidant properties, but has also been shown to be related metabolically to histidine and histamine, and to have immunopotentiating properties in vivo. It is shown here that carnosine presented topically or in the diet, potentiated the contact hypersensitivity reaction in hairless mice. Carnosine also prevented the systemic suppression of this reaction following exposure of the dorsal skin to ultraviolet B (UVB) radiation. Furthermore, carnosine prevented the systemic suppression caused by a topically applied lotion containing cis urocanic acid, indicating that it may act in competition with this UVB photoproduct which is believed to initiate many of the suppressive effects of UVB radiation. PMID- 8436409 TI - An analysis of the relationship between gamma delta T cell receptor V gene usage and non-major histocompatibility complex-restricted cytotoxicity. AB - gamma delta T cells are capable of mediating non-major histocompatibility complex (MHC) restricted lysis of a variety of tumour cell lines. The mechanism of this lysis and its significance in tumour immunity are not clear. We have used a panel of five malignant mesothelioma (MM) cell lines, as well as standard tumour targets K562 and Daudi, to investigate some of the factors which could be involved in non-MHC restricted cytotoxicity mediated by gamma delta T cells. Individual MM cell lines, representing a panel of lines derived from a single cell type, varied in their susceptibility to lysis by gamma delta T cell clones. Individual gamma delta T cell clones also showed unique cytotoxic profiles, and differed in their cytotoxic potential. T cell receptor (TCR) V gamma gene usage correlated with the ability of clones to lyse Daudi or K562; clones lysing Daudi expressing V gamma 9 and clones lysing K562 expressing V gamma I subgroup genes. No strict correlation between V gamma and V delta gene usage and MM reactivity was, however, demonstrable. There was also no correlation between gamma delta T cell lysis of MM cell lines and the capacity of gamma delta T cells to produce interferon-gamma, tumour necrosis factor-alpha, interleukin-2 or interleukin-4, nor with their expression of CD8. PMID- 8436410 TI - Multiple levels of post-transcriptional regulation of collagenase (matrix metalloproteinase 1) in an epithelial cell line. AB - Multiple levels of regulation of collagenase (matrix metalloproteinase 1; MMP-1), have been demonstrated in a clonal rat epithelial cell line (A5P/B10). Secreted enzyme could not be demonstrated in culture medium from A5P/B10 cells but, using antibodies specific for collagenase, the enzyme was detected within the cytoplasm and on the surface of the cells. A probe for rat collagenase could not detect a signal for mRNA in the cytoplasm while nuclear run-on data demonstrated that the gene for collagenase was being transcribed. Incubating the cells with 12-O tetradecanoylphorbol-13-acetate (TPA) significantly increased cytoplasmic mRNA levels and slightly increased the intensity of staining in permeabilized cells, but collagenase activity was still not detected in the conditioned medium. This indicated that the protein was being synthesized by the TPA-treated cells but was not being secreted into the medium. These data suggest that the secretion of collagenase may be regulated both following transcription and after the completion of translation and it is suggested that multiple levels of control may be operating to determine the rate of collagenase release and hence, the rate of collagen turnover. PMID- 8436411 TI - The trophoblast as an integral component of a macrophage-cytokine network. AB - The trophoblast, an epithelial cell of fetal origin that forms the physical barrier between the mother and developing conceptus, becomes a component of the host immune system during pregnancy. Of the classical immune cells, it most closely resembles the macrophage, also present in high numbers in the pregnant uterus. The macrophage and trophoblast, as cell classes, share characteristics such as phagocytosis, syncytialization, invasiveness, expression of the proteins CD4, CD14, IgG receptor (FcR), non-specific esterase, granulocyte macrophage-CSF (GM-CSF), colony stimulating factor 1 (CSF-1), interleukin-1 (IL-1), interleukin 6 (IL-6), tumour necrosis factor (TNF-alpha), transforming growth factors (TGF), platelet-alpha derived growth factor (PDGF) and receptors for these cytokines. In the uterus both cell types appear regulated by a common element, the uterine epithelium, that secretes cytokines such as CSF-1, GM-CSF, TNF alpha, TGF beta, IL-6, and leukaemia inhibitory factor (LIF) that target both macrophages and trophoblasts. The common characteristics and regulation that make teleological sense in terms of co-ordinating local uterine immunity during pregnancy may also be important in transmission of congenital diseases such as AIDS. The production by the uterine epithelium of a number of cytokines previously only associated with mononuclear phagocyte production and function predicts the existence of a similar, but broader, shared cytokine network encompassing trophoblast and the principal immune regulatory cell, the T lymphocyte. PMID- 8436412 TI - Adhesive interactions in thymic development: does selective expression of CD45 isoforms promote stage-specific microclustering in the assembly of functional adhesive complexes on differentiating T lineage lymphocytes? AB - CD45 isoform transitions appear to play essential roles in both life and death, and correlate with the stages of thymocyte development during which there is a change in physical location from medullary and/or outer cortical areas to the inner cortex. This work speculates that CD45 isoforms, through a focal role in the assembly of adhesive complexes mediated by the external domains, participate in the maintenance and/or modulation of migratory behaviour by differentiating thymocytes, or alternatively in the anchoring of thymocytes in a generative micro environment. The objective of the sections that follow is to formulate the hypothesis that CD45 isoforms, through their differential interactions with adhesion molecules expressed by T cells, profoundly influence cell motility and consequent micro-environmental localization. An adhesive assembly of CD45 and adhesion molecules on the outside, and of the adhesive complex with the cytoskeleton on the inside, would promote CD45-mediated regulation of adhesion/de adhesion through lateral external interactions mediated by external domains of CD45 isoforms, through enzymatic modulation of the cytoplasmic domains of adhesion molecules by the CD45 tyrosine phosphatase activity, and through phosphatase control of cytoskeletal assembly and disassembly. PMID- 8436413 TI - Transient retention of Strongyloides ratti in the caecal mucosa during infection in mice. AB - Adult worms of Strongyloides ratti, after elimination from the small intestine, were retained in the caecum for at least three days during the infection in mice. This retention was a biological event but not due to a simple mechanical trapping in faeces. In addition to the local mucosal mastocytosis, eosinophil infiltration was remarkable in the caecum around day 10 when adult worms were expelled from there. PMID- 8436414 TI - Immunoglobulin constant kappa gene alleles in twelve strains of mice. AB - Genomic DNA for the immunoglobulin (Ig) constant kappa Igk-C gene region was amplified by the polymerase chain reaction (PCR) method and sequenced from twelve commonly used inbred mouse strains. PCR products were used directly as templates in dideoxy-DNA-sequencing, a method which avoids the sequencing errors caused by Taq polymerase, since no cloning step is required. In restriction fragment length polymorphism (RFLP) studies the SJL mouse strain has been shown to belong to a Igk-C allogroup different from other common inbred mouse strains. The BALB/c Igk C region was sequenced earlier, but our Igk-C sequences clarify the situation and confirm the existence of three Igk-C alleles in inbred mice (Mus musculus domesticus). Mice belonging to the kappa (Igk) haplotype e (SJL) have allele c of the Igk-C gene. The strains belonging to the kappa haplotype [a albino strain, K subline (AKR), PL and d (C58)] have allele a, and all other eight strains belonging to three different Igk haplotypes (b, c, and f) use allele b of the gene. Allele b has at least one (possibly two) nucleotide differences from allele a in the Igk-C region, but five compared to allele c. The allelic sequences also predict two allotypic kappa polypeptide chains among twelve inbred strains. Alleles a and b encode identical polypeptides, but allele c (SJL) has a conserved lysine to arginine substitution in residue 142. PMID- 8436415 TI - A polymorphic system related to but genetically independent of the chicken major histocompatibility complex. AB - Analyses of the major histocompatibility complex (Mhc) in chickens have shown inconsistencies between serologically defined haplotypes and haplotypes defined by the restriction fragment patterns of Mhc class I and class II genes in Southern hybridizations. Often more than one pattern of restriction fragments for Mhc class I and/or class II genes has been found among DNA samples collected from birds homozygous for a single serologically defined B haplotype. Such findings have been interpreted as evidence for variability within the Mhc haplotypes of chickens not detected previously with serological methods. In this study of a fully pedigreed family over three generations, the heterogeneity observed in restriction fragment patterns was found to be the result of the presence of a second, independently segregating polymorphic Mhc-like locus, designated Rfp-Y. Three alleles (haplotypes) are identified in this new system. PMID- 8436416 TI - Characterization of a V kappa family in Mus musculus castaneus: expansion at the subset level. AB - We have examined the same kappa chain variable (V kappa) region family in several mouse species in order to observe short-term, incremental change at immunoglobulin (Ig) multigene loci. In the present study, the Igk-V24 family has been characterized in a Mus m. castaneus colony derived from individuals originating in Thailand and compared to the same family in Mus m. domesticus (BALB/c) and Mus pahari, representing about 1-2 and about 5-9 million years of evolution, respectively. Southern hybridization of genomic DNA with a probe encoding the prototype Igk-V24 coding region reveals restriction fragment patterns indicative of two distinct M. m. castaneus haplotypes. These haplotypes appear to result from an unequal recombination between similar gene arrays, as their restriction patterns are unique but contain many common fragments. The complexity of these patterns indicates a marked expansion in the Igk-V24 family of M. m. castaneus relative to BALB/c and M. pahari. Additional analyses using probes specific for individual subsets demonstrate that the expansion is not general throughout the entire family, but is restricted to particular subsets and therefore to relatively short chromosomal segments. One subset alone accounts for most of the expansion and comprises over 40% of the entire M. m. castaneus family. The wide range of Igk-V24 family complexity seen among M. m. castaneus, M. m. domesticus, and M. pahari, as well as among the different M. m. castaneus family subsets, suggests a model of random evolution in V kappa family copy number rather than one which is selective. PMID- 8436417 TI - Characterization of a V kappa family in Mus musculus castaneus: sequence analysis. AB - To examine genetic variation at immunoglobulin (Ig) multigene loci over short spans of evolutionary time, we have compared members of an Ig kappa chain variable (V kappa) region family from several mouse species. In this study, seven unique Igk-V24 family members have been isolated from Mus m. castaneus and characterized by nucleotide sequence determination for comparison to their counterparts in Mus m. domesticus (BALB/c), and Mus pahari, representing 1-2 million years of evolution in the former case and 5-8 million years in the latter. Parsimony, together with evolutionary distances calculated for various pairs of Igk-V24 family coding regions, relate all family members to a common progenitor existing roughly 24 million years ago (Mya). A significant portion of the M. m. castaneus family consists of pseudogene segments in various degrees of progressive degeneration. The substitution patterns and divergence rates for all gene segments are characteristic of their respective subsets, especially in the areas flanking the coding regions. Complex and variable patterns of diversity are seen in potentially expressed coding regions, which appear to reflect quite different selective pressures on various subregions within the V kappa protein domain. These results indicate that evolutionary pressures are operating at the level of family subsets, their individual members, and subregions within similar molecules. PMID- 8436418 TI - Cloning and sequence analysis of cDNAs encoding the MHC class II beta chain in Atlantic salmon (Salmo salar). AB - Atlantic salmon (Salmo salar) cDNAs encoding the major histocompatibility complex (Mhc-Sasa) class II beta chain were isolated from a leucocyte library by a polymerase chain reaction (PCR) approach. Three different cDNAs (c144, c22, and c157) encoding the entire mature beta chain have been analyzed. Clone c144 differs from clone c157 in 12.6% of the nucleotides in the beta 1-encoding region. The corresponding differences between clones c144 and c22, and clones c22 and c157, are 10.3% and 5.2%, respectively. This variation is, at least in part, most likely attributable to allelism. The similarity indices between the highly conserved beta 2 domains from Atlantic salmon and corresponding sequences from humans (DQ beta), chicken (BL beta), carp (TLAII beta-1), and rainbow trout (O.M. No. 55) are 45%, 40%, 66%, and 97%, respectively. Variable residues in the beta 1 domains from Atlantic salmon correspond with polymorphic sites of beta 1 domains from higher vertebrates. The frequency of substitutions in the beta 1-encoding region exceeds that in the 3'-untranslated (UT) region with several folds, indicating extensive beta 1 polymorphism in Atlantic salmon. PMID- 8436419 TI - HLA-DP/DR interaction in early onset pauciarticular juvenile chronic arthritis. AB - We investigated the polymorphic second exon of the HLA-DPB1 and HLA-DRB1 genes, using in vitro DNA amplification by polymerase chain reaction (PCR) and oligonucleotide hybridization in 136 patients with early onset pauciarticular juvenile chronic arthritis (EOPA-JCA) and 199 healthy controls. The analysis of the HLA-DRB1 system revealed that most of the DRB1 alleles are not indifferent with respect to susceptibility to EOPA-JCA. There is a hierarchy of susceptible (DRB1*08, DR5), "permissive" (DRB1*01), moderately "protective" (DR2, DRB1*04), and "protective" (DRB1*07) alleles. In contrast, no hierarchy could be shown for the HLA-DPB1 system. DPB1*0201 was found to be susceptible. The relatively frequent alleles DPB1*0402 and DPB1*0401 seem to be indifferent. The associations with DPB1*0201, DR5, and DRB1*08 are independent of each other: that is to say they, are not brought about by linkage disequilibrium. The susceptible alleles DPB1*0201 and DR5 show evidence for interaction in the pathogenesis of EOPA-JCA. Interaction seems likely between DPB1*0201 and DRB1*08, DR5 and DRB1*08, or between DR6 and DRB1*08. The strongest interaction exists between DPB1*0201 and a common DQ factor associated with both DR5 and DRB1*08. Finally, we observed a hierarchy among the various marker combinations, where the risk of developing EOPA-JCA increases with the number of associated markers present in an individual. PMID- 8436420 TI - Polymorphism of the tumor necrosis factor beta gene in systemic lupus erythematosus: TNFB-MHC haplotypes. AB - We investigated the Nco I restriction fragment length polymorphism (RFLP) of the tumor necrosis factor beta (TNFB) gene in 173 patients with systemic lupus erythematosus (SLE), 192 unrelated healthy controls, and eleven panel families, all of German origin. The phenotype frequency of the TNFB*1 allele was significantly increased in patients compared to controls (63.6% vs 47.1%, RR = 1.96, p < 0.002). The results of a two-point haplotype statistical analysis between TNFB and HLA alleles show that there is linkage disequilibrium between TNFB*1 and HLA-A1, Cw7, B8, DR3, DQ2, and C4A DE. The frequency of TNFB*1 was compared in SLE patients and controls in the presence or absence of each of these alleles. TNFB*1 is increased in patients over controls only in the presence of the mentioned alleles. Therefore, the whole haplotype A1, Cw7, B8, TNFB*1, C4A DE, DR3, DQ2 is increased in patients and it cannot be determined which of the genes carried by this haplotype is responsible for the susceptibility to SLE. In addition, two-locus associations were analyzed in 192 unrelated healthy controls for TNFB and class I alleles typed by serology, and for TNFB and class II alleles typed by polymerase chain reaction/oligonucleotide probes. We found positive linkage disequilibrium between TNFB*1 and the following alleles: HLA-A24, HLA-B8, DRB1*0301, DRB1*1104, DRB1*1302, DQA1*0501, DQB1*0201, DQB1*0604, and DPB1*0101. TNFB*2 is associated with HLA-B7, DRB1*1501, and DQB1*0602. PMID- 8436421 TI - A multigene family on human chromosome 12 encodes natural killer-cell lectins. AB - We previously isolated a series of cDNA clones designated NKG2-A, B, C, and D from a human natural killer (NK) cell library. These transcripts encode a family of type II integral membrane proteins having an extracellular Ca(2+)-dependent lectin domain. The predicted peptides share structural similarities and amino acid sequence similarity with known receptor molecules. In this report, the genomic organization and mRNA expression of each of the genes were studied by using transcript-specific probes. Southern blot experiments reveal that the probes cross-hybridize with a maximum of five genes at high stringency. By probing a Southern blot prepared from a series of hamster/human hybrid somatic cell lines, we demonstrated that all of the hybridizing fragments occur on human chromosome 12. No gene rearrangement and little restriction fragment length polymorphism (RFLP) was observed with these probes. mRNA expression of the NKG2 genes occurred in NK cells and some T cells but not in other hematopoietic cell types or in other tissues tested. Each of the transcripts occurred in all three of the NK cell lines tested: however, the genes were differentially regulated in T cells. NKG2-D was expressed in nine of fourteen T-cell clones or lines in the panel, whereas NKG2-A/B was expressed in three and NKG2-C was expressed in only one. Expression of each of the transcripts was upregulated following T-cell growth factor (TCGF)-induced activation of a cloned NK cell. The limited distribution of these proteins and their sequence similarity with known receptor molecules suggest that they may function as receptors on human NK cells. PMID- 8436422 TI - The genes for CD37, CD53, and R2, all members of a novel gene family, are located on different chromosomes. AB - CD37, CD53, and R2 leukocyte surface antigens are members of a novel family of structurally related proteins. They all have four transmembrane-spanning domains with a single major extracellular loop. The CD37 is expressed on B cells and on a subpopulation of T cells. The CD53 is known as a panleukocyte marker. The R2 protein is an activation antigen of T cells. The CD37, CD53, and R2 genes were assigned with the help of human/rodent somatic cell hybrids and human-specific probes to human chromosomes 19, 1, and 11, respectively. For the regional assignment, various deletion hybrids were used to map CD37 to 19p13-q13.4, CD53 to 1p12-p31, and R2 to 11p12. PMID- 8436423 TI - Molecular cloning of major histocompatibility complex class I cDNAs from Atlantic salmon (Salmo salar). PMID- 8436424 TI - Molecular cloning of equine CD44 cDNA by a COS cell expression system. PMID- 8436425 TI - Two new HLA-DPB1 alleles from Java, Indonesia. PMID- 8436426 TI - A novel HLA-DRB1-DR2 allele associated with HLA mistyping. PMID- 8436427 TI - Report on an IARC working group meeting on some naturally occurring substances. PMID- 8436428 TI - Review article: epidemiology of male breast cancer. A meta-analysis of published case-control studies and discussion of selected aetiological factors. AB - Male breast cancer is a rare tumour in all parts of the world. About 1% of all breast cancers occur in men, but the male/female ratio is higher among black than among white populations. This effect can be seen in US cancer registries and even more markedly in African data. A positive correlation exists on a population scale between male breast cancer and prostate cancer. Seven case-control studies of male breast cancer are available, and a pooled analysis was conducted of the most commonly suspected risk factors. Male breast cancer appears to be associated with marital status: Mantel-Haenszel exposure odds ratio (EOR) for never married = 1.6; 95% confidence limits (CL) = 1.1, 2.3, religion (EOR for being Jewish = 2.1; 95% CL = 1.4, 3.2), previous breast pathology (EOR for positive history of benign breast disease = 2.7; 95% CL = 1.7, 4.2), gynaecomastia (EOR for positive history = 6.2, 95% CL = 3.4, 11.4), previous testicular pathology (EOR for positive history = 2.2; 95% CL = 1.5, 3.3), previous liver diseases (EOR for positive history = 1.6; 95% CL = 1.0, 2.4) and family history of breast cancer (EOR for first-degree relative with breast cancer = 2.5; 95% CL = 1.7, 3.7). No association is found with smoking history. Other potential risk factors such as reproductive history, education, occupation, anthropometric variables, association with various diseases, and specific exposures such as drug use, were not systematically evaluated in all studies and provide sometimes contradictory results, possibly due to small numbers of exposed subjects. Overall, the analytical epidemiology of male breast cancer presents similarities with the epidemiology of female breast cancer, with a potential role of factors related to hormonal status, relative hyperoestrogeny in men being potentially linked to increased risk of disease. Genetics may also play a role, with high risk linked to a familial history of breast cancer, and with a major risk in patients with Klinefelter's syndrome. PMID- 8436429 TI - Dietary carcinogens and the risk for glioma and meningioma in Germany. AB - A population-based case-control study was performed in South-West Germany in 1987/88 with 115 histological confirmed glioma and 81 meningioma cases and 418 randomly selected controls. On the basis of information from a food-frequency questionnaire and questions on food preparation and food supply, the role of dietary carcinogens, in particular N-nitroso compounds or their precursors, on risk for glioma and meningioma were analyzed by multiple logistic regression. Eleven food groups were investigated. The intake of processed meat was significantly associated with an increased risk of glioma. The intake of any food group was not significantly related to meningioma risk. Among single meat products, a significantly higher risk of glioma was found for cooked ham, processed pork meat and fried bacon. For the consumption of 3 N-nitrosamines, assessed from the intake of processed meat and cheese, significant positive relations to glioma risk were found. These N-nitrosamines were also related to meningioma risk, although to a less pronounced extent. The risk for occurrence of glioma was significantly increased for those using vegetable fat frequently for deep frying, as compared with non-users. For the dietary intake of nitrate, nitrite, vitamin C, specific alcoholic beverages, total alcohol, and water from a non-central supply, no elevated risk was found in this study. PMID- 8436430 TI - Ganglioside expression on human malignant melanoma assessed by quantitative immune thin-layer chromatography. AB - The ganglioside composition of 20 human malignant melanomas and 5 normal tissues (muscle, spleen, kidney, liver and brain) was analyzed by high-performance thin layer chromatography (HPTLC) and immune HPTLC using a panel of antiganglioside monoclonal antibodies, and quantified by photodensitometry. The most prominent gangliosides were GM3 and GD3, present in all 20 melanomas; however these were expressed in the 5 normal tissues as well. GD2, GM2, GT3 and 9-O-Ac-GD3 were each expressed in at least 17 of 20 melanomas, but distribution on the normal tissues examined was largely restricted to brain. The detection of several additional glycolipids was studied. GMI was highly expressed in normal brain tissue, but was not detected in any melanoma biopsies, and SGPG was detected in neither. Fuc-GMI was identified in 3 melanoma specimens and a base-sensitive ganglioside, not previously identified in melanoma, was detected in 4 of 20 melanomas with the anti-GD2 MAb 3F8. This compound is most likely O-acetylated GD2. GD3 lactones were identified in 16 of 20 melanoma biopsies, however the proportion that are naturally occurring rather than artifacts of extraction is unclear. The total expression of the more restricted gangliosides (GM2, GD2, GT3 and 9-O-Ac-GD3) in these 20 melanomas ranged between 2.4 and 102.5 micrograms/g, representing 8 x 10(6) to 3 x 10(8) ganglioside molecules per cell. This number of tumor-surface antigens provides the rationale for a polyvalent anti-melanoma vaccine containing GM2, GD2, GT3 and 9-O-Ac-GD3. PMID- 8436431 TI - Trends in non-melanocytic skin cancer treated in Australia: the second national survey. AB - An Australia-wide survey in 1985 recorded the highest rates of medically treated non-melanocytic skin cancer (NMSC) ever reported. We report the findings of a repeat survey conducted in 1990. This second survey confirmed the differences, by age, sex, body site, latitude, country of birth and skin reaction to strong sunlight, that were observed in 1985. Over the 5-year period certain changes were noted: the incidence of NMSCs increased by 19%, of basal-cell carcinomas (BCC) by 11% and of squamous-cell carcinomas (SCC) by 51%. With advancing age, men and women differed in their incidence, and this difference was greater for SCC than for BCC. Log-linear modelling, however, failed to detect either a cohort or a survey effect between the 2 surveys. The proportional distribution of BCCs and SCCs by body site indicated an increase in BCCs on the trunk in both men and women, and half the proportion of SCCs on the head and neck in women as compared with men. The latitudinal gradients observed in 1985 were even stronger in 1990; the population living north of 37 degrees S experienced a 30% increase in the incidence of treated NMSC between 1985 and 1990, while the population living south of 37 degrees S had a 25% decrease. The implications of these findings for cancer-control initiatives are discussed. PMID- 8436432 TI - Mother-to-child transmission of human T-lymphotropic virus type I (HTLV-I): an extended follow-up study on children between 18 and 22-24 years old in Okinawa, Japan. AB - The significant difference observed between the seroprevalence of HTLV-I in adults and in children is as yet unexplained. To evaluate a hypothetical explanation of the existence of seroconversion cases of "seronegative carriers" for this phenomenon, 21 of 55 children who had been born to seropositive mothers and who remained seronegative until the age of 18 years were further followed up at the ages of 22 and/or 24 years. None of the 21 seronegative children born to seropositive mothers seroconverted, either at 22 years or at 24 years. In addition, the polymerase-chain-reaction (PCR) technique could not prove the existence of the HTLV-I provirus genome in peripheral mononuclear cells (PBMC) of 10 of these children. Our results fail to prove the possibility of viral latency of HTLV-I in mother-to-child transmission. Therefore, the hypothetical seroconversion of "seronegative carriers" after adulthood cannot be an explanation. PMID- 8436433 TI - Cigarette smoking, alcohol, tea and coffee consumption and pancreas cancer risk: a case-control study from Opole, Poland. AB - A population-based, case-control study of pancreas cancer was undertaken in Opole, Poland, within the framework of the SEARCH Programme of the International Agency for Research on Cancer: this is the first aetiological study of pancreas cancer reported from Poland where the reported mortality rate has doubled since 1963. This study of pancreas cancer has provided some further supporting evidence of an association between increased pancreas risk with increasing levels of cigarette smoking. The risk rose with increasing lifetime cigarette consumption with a trend which was weakly significant (p = 0.061). Findings regarding lifetime tea and coffee consumption were not consistent with intake of either beverage increasing the risk of this disease. There was a strongly significant trend of decreasing risk with increasing lifetime consumption of tea (p < 0.001), which was also apparent when the analysis was restricted to subjects who were interviewed directly. For coffee consumption, which is low in Poland, there was also a negative association apparent in the data which was not statistically significant among the sub-set of subjects who were directly interviewed. The findings regarding alcoholic beverages were overall null, although the weakly positive trend in risk with spirits consumption (p = 0.71) may deserve further investigation in view of the special nature of the source of spirits (vodka) in Poland. PMID- 8436434 TI - Orthotopic transplantation of histologically intact clinical specimens of stomach cancer to nude mice: correlation of metastatic sites in mouse and individual patient donors. AB - Fresh surgical specimens derived from 36 patients with advanced stomach cancer were orthotopically transplanted in nude mice using histologically intact tissue. Twenty of 36 patient tumors gave rise to locally growing tumors in the mice. All 20 patients whose stomach tumors resulted in local growth in the nude mice had clinical lymph-node involvement, whereas 8 of the other 16 patients whose tumors were rejected had lymph-node involvement. There was a statistical correlation (p < 0.01) between local tumor growth in nude mice and clinical lymph-node involvement. Of the 20 cases resulting in local growth in the nude mice, 5 had clinical liver metastases and all 5 cases resulted in liver metastases in the nude mice. Of the 20 cases, 6 had clinical peritoneal involvement of their tumor, and of these 5 resulted in peritoneal metastasis in the nude mice. There were statistical correlations (p < 0.01) for both liver metastases and peritoneal involvement between patients and mice. These results indicate that, after orthotopic transplantation of histologically intact stomach cancers from patients to nude mice, the subsequent metastatic behavior of the tumors in the mice closely correlated with the course of the tumors in the patients. PMID- 8436435 TI - Establishment and characterization of 7 ovarian carcinoma cell lines and one granulosa tumor cell line: growth features and cytogenetics. AB - The characteristics of 7 newly established ovarian carcinoma cell lines and one granulosa tumor cell line obtained from tumor samples of 7 patients with varying histology of the primary tumor are reported. The cell lines were isolated from 5 serous carcinomas, a mucinous carcinoma, an endometrioid carcinoma and a granulosa cell tumor. All cell lines were passaged at least 25 times and showed stable growth rates. Colony-forming efficiency varied on plastic from 2 to 57% and in agar from 0.01 to 9.30%. The DNA index of the granulosa tumor cell line was diploid, while the ovarian carcinoma cell lines were all aneuploid. In 2 cell lines polyploidisation occurred during culturing. A thorough cytogenetic analysis of 7 cell lines revealed that the granulosa tumor cell line has only minor cytogenetic abnormalities (+5, 22q+). In contrast, the epithelial ovarian-cancer cell lines gave very complex karyotypes with numerous markers and structurally rearranged chromosomes. The chromosomes most often in excess were 15 and 20. Structural rearrangements of chromosomes 1, 3, 7 and 11 were prominent in all ovarian cell lines. In addition, we found changes in chromosomes X, 5, 8 and 13 that have rarely been described before. PMID- 8436436 TI - Correlation between the lung distribution patterns of Lu-ECAM-1 and melanoma experimental metastases. AB - Lu-ECAM-1 is a 90-kDa lectin-like, melanoma-cell-binding endothelial-cell adhesion molecule that mediates colonization of the lungs by B16-F10 melanoma cells. The well-known formation of pleural and sub-pleural B16-F10 melanoma colonies is correlated quantitatively with prominent histochemical staining of endothelia of pleural capillaries and sub-pleural venules with anti-Lu-ECAM-1 MAb 6D3. The less frequent endothelial staining of perivenous and peribronchial venules is associated with fewer B16-F10 colonies in these locations, and the occasional segmental staining of pulmonary veins coincides with rare tumor nodules which usually expand in an asymmetric fashion around these veins. Lu-ECAM 1 is also expressed on endothelia of some tumor vessels, indicating that these vessels are recruited from the same host blood vessels that originally caused the arrest of blood-borne B16-F10 melanoma cells. The close association between the lung distribution patterns of Lu-ECAM-1-positive blood vessels and experimental melanoma metastases is further evidence of the importance of endothelial-cell adhesion molecules in the formation of metastases. PMID- 8436437 TI - Inhibition of N-linked oligosaccharide processing in tumor cells is associated with enhanced tissue inhibitor of metalloproteinases (TIMP) gene expression. AB - Previous studies on tumor-cell glycosylation mutants and drugs which inhibit oligosaccharide processing suggest that expression of sialylated and highly branched complex-type N-linked oligosaccharides is required for efficient tumor cell metastasis. These observations prompted the present investigation, in order to determine whether loss of sialylated and highly branched complex-type oligosaccharide in cellular glycoproteins might affect the expression of genes, particularly of genes which can influence the malignant phenotypes. Swainsonine, an inhibitor of Golgi alpha-mannosidase II, has previously been shown to inhibit invasion in vitro and reduces solid tumor in vivo. Metastatic sub-lines of the SP1 murine mammary carcinoma cells cultured in the presence of swainsonine for 48 hr showed approximately 3-fold enhancement of TIMP mRNA levels, while urokinase (uPA) transcripts remained unchanged. To determine whether swainsonine's effect on TIMP mRNA levels was related to inhibition of oligosaccharide processing, we examined somatic glycosylation mutants with processing defects which attenuate metastatic potential. The Golgi UDP-Gal transport defect in murine MDAY-D2 lymphoma cells, Chinese hamster ovary cells (CHO) and human MeWo melanoma cells (i.e., D35W25, Lec8, 3S5 cell lines, respectively) was associated with increased TIMP mRNA levels. A revertant of Lec8 showed a return to the wild-type levels of TIMP mRNA, consistent with a causal relationship between the glycosylation mutation and TIMP gene expression. Similarly, CHO and MDAY-D2 mutants defective in GlcNAc-TV (i.e., Lec4 and KBL-1 respectively), which also reduces metastatic potential, showed increases in TIMP transcript levels. Nuclear run-on assays showed that transcription of the TIMP gene was increased in cells where N-linked oligosaccharide processing was inhibited either by swainsonine or by a glycosylation mutation. The results suggest that cell-specific patterns of glycoprotein glycosylation in human, murine and hamster cell lines affects the transcription of select genes, including TIMP, which may influence the invasive phenotype. PMID- 8436438 TI - Anti-tumor activity of ceramides and glycosphingolipids in a murine tumor system. AB - The anti-tumor activity of 7 sphingolipids, 2 ceramides and 5 glycosphingolipids against the syngeneic murine ascitic tumors MH134 and MM102 in C3H mice was examined. Five of these compounds showed anti-tumor activity against the tumors, ceramide type-IV (Cer-IV) having the highest activity without cytotoxic or cytostatic activity. These results indicate that the fatty acid in ceramide and sugar chains binding to it affect the anti-tumor activity in vivo. The anti-tumor activity of Cer-IV depended on the time of treatment. Mice treated with Cer-IV one day after tumor implantation showed the highest rate of survival. The cured mice were resistant to rechallenge with the same tumor (MH134-->MH134, MM102- >MM102) but not with a heterologous tumor (MH134-->X5563, MM102-->X5563), indicating that the effect of Cer-IV may be due to in vivo induction of specific immunity. Studies with various antibodies demonstrated that the anti-tumor effect of Cer-IV was inhibited by all the antibodies tested (L3T4, Lyt-2, and Thy-1,2 T cells, macrophages, and TNF alpha) in the induction phase (before Cer-IV administration) and by the antibodies of L3T4 and TNF alpha in the effector phase (after Cer-IV administration). Therefore, the anti-tumor effect of Cer-IV in this system depended on the host immune response rather than on its direct cytotoxic and/or cytostatic action. PMID- 8436439 TI - In vivo and in vitro reactivity of rat spleen cells against regressor and progressor colon-cancer cell variants. AB - Previous reports demonstrated that progressor and regressor tumor-cell variants isolated from the same colon carcinoma chemically induced in a BD-IX rat differed in their capacity to induce an immune response. The present study was aimed at analyzing the characteristics of the responses to the regressor REGb and progressor PROb clones. Spleen cells from rats bearing early REGb tumors neutralized PROb cell tumorigenicity in a Winn-type local transfer assay, but responded occasionally to REGb and PROb cells in vitro. However, spleen cells from rats immunized by several injections of REGb and PROb cells strongly proliferated when cultured with PROb or REGb cells. This response was selective for the cell lines generated from the individual tumor at the origin of PROb and REGb lines, was dependent on CD4+ spleen cells, and was partially inhibited by an antibody against major histocompatibility complex class-II molecules. Although PROb cells shared tumor-rejection antigen(s) with REGb cells, splenocytes from PROb tumor-bearing rats did not neutralize PROb-cell tumorigenicity in vivo, nor did they proliferate when cultured with PROb or REGb cells in vitro. The unresponsiveness of spleen cells from PROb tumor-bearing rats was not due to the presence of immune suppressive cells, and a defect of antigen-presenting cells was shown to be unlikely. This unresponsiveness was limited to a lymphocyte subpopulation, since spleen cells from tumor-bearing rats responded normally to stimulation by PHA or allogeneic lymphocytes. These results strongly suggest that unresponsiveness of spleen cells from tumor-bearing rats is due to a tumor specific anergy of the lymphocyte clones able to respond to tumor-associated antigens. PMID- 8436440 TI - Binding activities of cis-platin-damage-recognition proteins in human tumour cell lines. AB - Proteins can be detected by South-western analyses of human tumour-cell extracts binding to double-stranded oligonucleotide DNA treated in vitro with the chemotherapeutic drug cis-diamminedichloroplatinum (II) (CDDP), but not to untreated DNA. The relative molecular masses of proteins binding to the CDDP treated double-stranded oligonucleotide are 25, 48 and 97 kDa. The binding activity of 2 of the CDDP-damage-recognition proteins, of relative molecular mass 48 and 97 kDa, is greater in a CDDP-resistant human ovarian tumour cell line than in the parental sensitive line. South-western analysis of a panel of human bladder cell lines and CDDP-sensitive testicular cell lines show consistent patterns of CDDP-damage-recognition proteins within each cell type, however with differences between the 2 cell types. Binding of the proteins to CDDP-damaged DNA and the altered binding activity detected in tumour cell lines suggests that alteration in damage-recognition proteins could play a role in tumour response to CDDP. PMID- 8436441 TI - Granulocyte-macrophage colony-stimulating factor stimulates the metastatic properties of Lewis lung carcinoma cells through a protein kinase A signal transduction pathway. AB - Expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) by metastatic Lewis lung carcinoma cells (LLC-LN7) was previously shown to contribute to the maintenance of phenotypic characteristics associated with an increased capacity to metastasize. In the present study, pre-incubation of LLC LN7 cells with neutralizing anti-GM-CSF antibodies diminished the capacity of the tumor cells to form experimental metastases after i.v. inoculation, while pre incubation with recombinant GM-CSF (rGM-CSF) increased formation of metastases. In the presence of rGM-CSF, the LLC-LN7 cells exhibited an increased capacity to migrate, invade through a reconstituted basement membrane, and adhere to lung tissue. Studies to identify the signal transduction pathway through which GM-CSF enhanced the in vitro metastatic properties of the LLC-LN7 tumor cells implicated protein kinase A (PKA). Signaling through PKA was suggested by the demonstration that the stimulation of tumor-cell motility by GM-CSF was blocked in the presence of the adenylate cyclase inhibitor nicotinic acid, or the PKA inhibitors A3 or KT5720. In addition, the role of PKA as a signaling mechanism for GM-CSF was assessed by using REV-LN7 cells, which are LLC-LN7 cells that have been stably transfected with an expression vector encoding a mutant PKA RI alpha subunit and which, in turn, express a cAMP-resistant PKA. Adherence and invasion by the PKA defective REV-LN7 cells were not stimulated by rGM-CSF, contrasting with the stimulation observed for wild-type LLC-LN7 cells. These data suggest that rGM-CSF can further enhance the in vitro metastatic characteristics of LLC-LN7 tumor cells and that this is dependent on signal transduction through PKA. PMID- 8436442 TI - Generation of cytotoxic antibodies to the B16 murine melanoma using a formalinized vaccine. AB - The goal of our experiments was to determine the extent to which the humoral response to a melanoma vaccine elicits the production of cytotoxic antibodies in tumor-challenged mice. Mice were immunized with a vaccine produced from formalinized extracellular antigens (FECA) derived from B16 F10 melanomas. The production of antibodies that recognized the vaccine preparation was determined by ELISA, as was their cross-reactivity with the B700 melanoma antigen. The antibodies were shown to be anti-proliferative by inhibition of tritiated thymidine incorporation into the DNA of cultured target cells and cytotoxic by assays for complement-mediated and antibody-dependent cellular cytotoxicity. Flow cytometric analyses indicated that approximately 60% of the target cells specifically bound antibody from the immune sera. These results confirm that B700 is a significant antigenic component of the FECA vaccine, and provide encouragement for this approach to developing useful melanoma vaccines. PMID- 8436443 TI - Association between timing of surgery during menstrual cycle and prognosis in pre menopausal breast cancer. PMID- 8436444 TI - Non coded C alpha, alpha-disubstituted amino acids. X-ray diffraction analysis of a dipeptide containing (S)-alpha-methylserine. AB - The crystal and molecular structure of the fully protected dipeptide Boc-Val-(S) alpha-MeSer-OMe has been determined by X-ray diffraction techniques. Crystals grown from ethyl acetate/n-pentane mixtures are tetragonal, space group I4(1), with cell parameters at 295 K of a = 15.307(2), c = 18.937(10)A, V = 4437.1A3, M.W. = 332.40, Z = 8, Dm = 0.99 g/cm3 and Dx = 0.995 g/cm3. The structure was solved by application of direct methods and refined to an R value of 0.028 for 1773 reflections with I > or = 3 sigma (I) collected on a CAD-4 diffractometer. Both chiral centers have the (S) configuration. The dipeptide assumes in the solid state an S shape. The urethane moiety is in the cis conformation, while the amide bond is in the common trans conformation. The conformational angles phi 1, psi 1 of the Val and phi 2, and psi 2 of the (S)-alpha MeSer fall in the F region of the phi-psi map. The isopropyl side chain of the Val residue has the (t, g-) conformation, while the Ser side chain has a g+ conformation. The hydrogen bond donor groups are all involved in intermolecular H-bond interactions. Along the quaternary axis the dipeptide molecules are linked to each other with the formation of infinite rows. PMID- 8436445 TI - Synthesis and biological activity of [L-hydroxyproline]3-tuftsin analogue and its alpha- or beta-O-D-glucosylated derivatives. AB - Syntheses are described of the Hyp3-tuftsin analogue and of its derivatives alpha or beta-O-glycosylated at the side chain function of the hydroxyproline residue. The carbohydrate-free tetrapeptide was prepared by reacting Z-Thr-Lys(Z)-OH with H-Hyp-Arg(NO2)-OBzl by the mixed anhydride procedure. In the synthesis of the alpha-glycosylated analogue the O-glycosyl amino acid was incorporated by reacting Boc-(Glc alpha+beta)Hyp-OH with H-Arg(NO2)-OBzl through the same procedure. The alpha-glucosylated dipeptide was isolated from the diastereomeric mixture, selectively deblocked, and acylated with Z-Thr-Lys(Z)-OH by the mixed anhydride procedure. In the preparation of the beta-glucosylated analogue the BOP procedure was used for reacting Boc-[Glc(Ac)4 beta]Hyp-OH with H-Arg(NO)2-OBzl was well as for the final coupling to tetrapeptide. Removal of protecting groups from crude tetrapeptides was achieved by catalytic hydrogenation. Deacetylation of the sugar moiety of the beta-glucosylated tetrapeptide was achieved by treatment with sodium methoxide in methanol. The synthetic compounds were isolated by ion exchange chromatography, and characterized by elemental analysis, amino acid analysis, optical rotation and proton NMR. Their capacity to evoke the release of interleukin 1 from mouse peritoneal macrophages and to modulate immunogenic activity of antigen-fed cells was evaluated, in comparison with tuftsin and rigin. All of the analogues were found to possess tuftsin-like activity. PMID- 8436446 TI - Isolation and characterization of two distinct gonadotropins, GTHI and GTHII, from bonito (Katsuwonus plelamis) pituitary glands. AB - Two distinct glycoproteins homologous to chum salmon GTHI and GTHII were isolated from the pituitary glands of a marine fish, the bonito (Katsuwonus plelamis), and characterized by amino acid sequence analysis in order to obtain additional evidence for duality of teleost GTHs. Glycoproteins were extracted from the pituitary glands, and intact GTHI and GTHII, consisting of two distinct subunits, were purified by ion-exchange chromatography on DEAE-cellulose, rpHPLC on Asahipak C4P-50 in alkaline buffer, and gel filtration on Superdex 75. The association of the subunits was stable in GTHI (39 kD) and unstable in GTHII (30 kD) in acidic conditions. Immunoblotting revealed that antisera against beta subunits of chum salmon GTHs reacted with GTHII, but not with GTHI. In addition, none of the GTHs was stained with antiserum against human TSH beta. Sequence analysis demonstrated that bonito GTHI beta is homologous to salmon GTHI beta with 43% sequence identity, and bonito GTHII beta is homologous to salmon GTHII beta with 67% identity. Sequence identity between bonito GTHI beta and GTHII beta was only 28%. Thus, it is evident that the bonito pituitary gland produces two chemically distinct gonadotropins homologous to chum salmon GTHs. PMID- 8436447 TI - Evaluation of biological activities of new LH-RH antagonists (T-series) in male and female rats. AB - A series of new highly potent LH-RH antagonists (T-series) has been synthesized in our laboratory. Among these analogs, antagonists [Ac-D-Nal(2), D-Phe(4Cl)2, D Pal(3)3, D-Lys(A2pr(Car)2)6, D-Ala10]LH-RH (T-140); [Ac-D-Nal(2)1, D-Phe(4Cl)2, D Pal(3)3, D-Lys(A2pr(Ac)2)6, D-Ala10]LH-RH (T-148); [Ac-D-Nal(2)1, D-Phe(4Cl)2, D Pal(3)3, D-Lys(A2pr(For)2)6, D-Ala10]LH-RH (T-151) and [Ac-D-Nal(2)1, D Phe(4Cl)2, D-Pal(3)3, D-Lys(A2bu(For)2)6, D-Ala10]LH-RH (T-159) were the most powerful. Antagonists T-140, T-148 and T-151 produced a complete blockade of ovulation in normal cycling rats at a dose of 1.5 micrograms/rat and antagonist T 159 at a dose of only 0.75 micrograms/rat. The inhibitory effects of compounds T 148, T-151 and T-159 on gonadotropin and sex steroid secretion were investigated in male and female rats. To determine their effect on LH levels in castrated male and ovariectomized female rats, T-148, T-151 and T-159 were injected subcutaneously in doses of 0.625 and 2.5 micrograms/rat. Blood samples were taken at different intervals for 48 h. All three compounds at either dose caused a significant (P < 0.01) decrease in LH levels for more than 6 h. Significant (P < 0.01) inhibition of LH lasted for more than 24 h following a dose of 2.5 micrograms sc of all 3 antagonists in both male and female rats. Serum FSH levels were also suppressed significantly for more than 48 h in castrated male rats by all three antagonists at a dose of 5 micrograms/rat sc.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8436448 TI - Sequence and solution conformation of the 20-residue peptaibols, saturnisporins SA II and SA IV. AB - Saturnisporins SA II and SA IV are the major components of the 20-residue peptaibol mixture isolated from a culture of the fungus Trichoderma saturnisporum. These peptides exhibit antibiotic activity against Staphylococcus aureus. Their sequences were derived from unequivocal methodology implying the combined use of positive ion FAB mass spectrometry and NMR: the majority of the sequences result from mass spectrometry fragmentations and the location of isomeric residues arises either from analysis of ROESY cross-peaks between contiguous amide protons or from heteronuclear 2J or 3J 1H-13C couplings detected in long-range 1H-13C COSY experiments. The sequence specific 1H and 13C NMR assignments are described. Saturnisporins SA II and SA IV exhibit similar secondary structures, as deduced from their ROESY patterns and 3JNHC alpha H coupling constant values, together with amide hydrogen-deuterium exchange rates and temperature coefficients of amide and carbonyl groups. An overall alpha helical structure is proposed, maintaining two regions of distortion to this regular structure; i) the N-terminal part, which contains 3(10) and mixed alpha 3(10) turns, and ii) the Aib10-Val15 region, including a Pro residue which accommodates a bend stabilized by two 3(10) H-bonds. PMID- 8436449 TI - Conformation of glutathione adduct and oxidized forms of platelet-derived growth factor. AB - The conformational properties of several platelet-derived growth factors (PDGFs) were characterized by circular dichroism (CD), Fourier transform infrared spectroscopy (FTIR), gel filtration and sedimentation equilibrium. Three different forms of disulfide linked dimer, PDGF-AA, PDGF-AB, and PDGF-BB, showed similar far UV CD spectra with evidence for slight beta-structure, but little evidence of other regular secondary structures. These spectra were, however, different from the far UV CD spectra of the glutathione adducts of PDGF-A and B, suggesting that the latter two proteins adopt different conformations in the absence of intra- or inter-molecular disulfide bonds. FTIR studies confirmed this by showing that the glutathione adducts of the PDGF-B protein have a significantly lower amount of regular secondary structures than PDGF-BB. Additionally, the increased bandwidths of the amide I components of the FTIR spectrum of the glutathione adduct indicates a more flexible structure relative to the dimeric form. Sedimentation equilibrium analysis showed that PDGF-BB is primarily a dimer and that the glutathione form is primarily a monomer. Thus, it was concluded that the glutathione derivative has little affinity to form non covalent dimers in neutral solution. PMID- 8436450 TI - Side reaction during the deprotection of (S-acetamidomethyl)cysteine in a peptide with a high serine and threonine content. AB - The acetamidomethyl (Acm) group is a widely used protecting group for the thiol of cysteine during the SPPS process. We prepared the amino terminal loop of the snake alpha-neurotoxin, [Cys3,Cys23, Ser17](1-24) amide, from the linear peptide [Cys(Acm)3,23,Ser17](1-24) amide obtained by SPPS. Three different methods of deprotection of Cys(Acm) and disulfide bond formation were used: iodine, thallium(III) trifluoroacetate and mercuric acetate/potassium ferricyanide. The iodine method failed to yield the expected peptide, and gave instead the mono iodinated tyrosine analog. The disulfide cyclized peptide obtained by thallium (III) or Hg(II) procedures displayed a MW value observed by mass spectrometry that was higher than the calculated value. The difference (MWobs-MWcalc) corresponded to a multiple of the Acm moiety, which is shifted intra- and/or intermoleculary. Furthermore, we observed, in addition to the Acm shift in the disulfide cyclized decapeptide with a highSer and Thr content (model peptide II), the dimerization phenomenon in the Tl(TFA)3 process. Therefore we conclude that a side reaction, a S--O(Ser,Thr) Acm shift, occurred during the Cys(Acm) deprotection. This shift was supported by the demonstration of Ser(O-Acm) formation in the reaction of Boc-(L)-Cys(Acm) with Tl(TFA)3 in the presence of an equimolar amount of (L)Ser. We report here the efficiency of a trivalent alcohol, glycerol, as scavenger in the both Tl(TFA)3 and mercuric/ferricyanide methods, in an attempt to circumvent this side-reaction during the disulfide bond formation step starting from a bis-Cys(Acm) peptide with a high Ser and Thr content, such as the N-terminal loop of neurotoxin, model peptide II or a similar peptide. PMID- 8436451 TI - Biology and culture: otolaryngology the interface. PMID- 8436452 TI - Pediatric otolaryngology procedures in the United States: 1977-1987. AB - Common pediatric otolaryngology inpatient procedures for the years 1977 through 1987 are analyzed utilizing data provided by the National Hospital Discharge Survey (NHDS) of the National Center for Health Statistics. The data available reveal that adenotonsillar surgery remains the most frequent inpatient surgical procedure performed on all children under age 15 in spite of a decline in both the total number of adenotonsillar procedures and the rate per 100,000 population of greater than two-fold over this 11 year period. The total number of myringotomies with and without insertion of ventilation tubes and the rate per 100,000 children also decreased by greater than threefold during the same time span. Although representative of inpatient, non-institutionalized health care, the NHDS suffers from its lack of data concerning surgery performed in freestanding, ambulatory surgical facilities and military hospitals. PMID- 8436453 TI - Brainstem auditory evoked potentials in young children before and after tympanostomy tube placement. AB - To evaluate the effect of tympanostomy tube placement upon the hearing function of infants and young children, brainstem auditory evoked potentials (BAEP) were recorded in a group of young children (mean age 22 mos) receiving this treatment for otitis media with effusion (OME). For comparison, a group of healthy infants with normal behavioral audiometry were also tested with BAEP. Hearing loss was estimated for each ear using peak V latency-intensity curves. To evaluate the immediate effect of tube placement, 98 ears in 52 children were tested immediately before and after tube insertion. The 63 ears with effusion had prolonged peak latencies that decreased significantly (P < 0.001) immediately after tube placement and a mean hearing loss estimate of 22 dB that improved significantly (P < 0.0001) to 11 dB immediately after tube insertion. The 35 ears without effusion at myringotomy had a mean hearing loss estimate of 8 dB that did not change significantly after tube insertion. To evaluate the short-term effect of tube presence, 39 ears in 25 children were tested 3 weeks to 18 months after tube insertion. The 28 ears with dry tubes had a mean hearing loss estimate of 3 dB, and the 11 ears with otorrhea had a mean hearing loss estimate of 31 dB. The magnitude of mean hearing loss estimates in these young children with OME and the improvement in hearing function with tube placement is similar to that reported in older children studied with BAEP and audiometry. The study groups with a history of otitis media that had resolved by the time of testing had isolated prolongation of mean III-V interpeak latencies compared to normals (P < 0.01). These studies show that BAEP techniques are useful in estimating hearing loss in children with OME who are difficult to test by behavioral audiometry and show changes in rostral brainstem transmission in very young children with a history of OME. PMID- 8436454 TI - T-tubes: a retrospective review of 1274 insertions over a 4-year period. AB - 1274 T-tubes were inserted for persistent otitis media with effusion in 661 patients over a 4-year period. The peak ages for insertion were between 4 and 7 years, and by 11 years the condition is uncommon. If a tube has not extruded spontaneously after 30 months it becomes increasingly less likely to do so. Complications were persistent perforations (32.6%), tympanosclerosis (23.6%), repeated otorrhoea or tympanic membrane granulations (21%), and impacted wax (10.9%). Forty-eight percent of patients experienced one or more complication in the study period, and the complication rate increased dramatically in patients whose tubes had remained in situ for longer than 36 months. After this time surgical removal is recommended. PMID- 8436455 TI - Myiasis in children: the Indian perspective. AB - A retrospective analysis of 94 cases of childhood myiasis admitted over a 6-year period is presented. Children formed 37.9% of all cases of myiasis. More than 50% of the children were less than 5 years of age and most (96.8%) belonged to a rural background. Of the 94 cases, 81 (86.16%) were of aural, 11 (11.7%) of nasal and 2 (2.12%) of ocular myiasis. The peak incidence was seen from September to October. The main symptoms in aural myiasis were passage of worms (81.48%), discharge (44.44%) and pain (41.97%). In nasal myiasis epistaxis (100%), foul smell (100%) passage of worms (90.9%) and pain (72.72%) were the prime presenting symptoms. All patients were treated with chloroform and turpentine oil in the ratio 1:4 which was followed by manual removal of the maggots and were made maggot-free in 2-3 days. No complications were seen. PMID- 8436456 TI - Secretory otitis media and mastoid air cell development. AB - Controversy continues over the factors involved in the development of the mastoid air cell system (MACS). This study examines the effect of persistent secretory otitis media with effusion (SOME) on the development of the MACS. Thirty-one children, aged 4, were drawn from a cohort of cleft palate children in a multi centre, prospective otological study set up in 1984. The initial presence of SOME was assessed by otoscopy, tympanometry and bilateral myringotomy, performed under the same anaesthetic as surgical repair of the cleft lip or palate. Only one ear in each child was ventilated with a tube and the other, the control ear, was assessed by regular follow-up otoscopy and tympanometry. The persistence of SOME after palate repair in over 70% of the non-ventilated ears in 4 years olds and the presence of a contralateral ventilated middle ear provides the perfect model for assessing the effect of SOME on MACS development. Plain, lateral mastoid X rays were assessed by planimetry to give a well accepted measurement of mastoid pneumatization. Nine children were excluded from analysis as they did not meet the strict criteria of one persistently ventilated middle ear and one with persistent SOME. 22 children (44 ears) were available for analysis, 9 children were tubed at 3 months and 13 were tubed at 12 to 16 months. In 19 of the 22 ears the mastoid air cell system was larger on the tubed side.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8436457 TI - The effect of post-operative instructions on recovery after tonsillectomy and adenoidectomy. AB - The effect of postoperative diet and activity instructions on the recovery rate after tonsillectomy and adenoidectomy (T & A) was assessed in 92 children ages 3 to 14 years. Two types of postoperative instruction were randomly assigned: 'Restricted', which advised limited, stay at home activities and a soft food liquid diet for 7-10 days, and 'nonrestricted', which advised return to activity and diet as tolerated by the child. Parental evaluation of the levels of pain, activity, and diet using an equal intervals scale was obtained. The number of doses of pain medication, the types of food eaten and postoperative complications were also recorded. No significant differences were found between the two groups in pain level, activity tolerance, return to normal diet, and numbers of doses of pain medication at day 3 and day 7 after surgery. More 'junk' food and spicy foods were eaten in the 'nonrestricted' group. Postoperative hemorrhage requiring intervention occurred in one child in each group. Implications for the children and their families undergoing T & A are discussed with attention to a review of the literature. PMID- 8436458 TI - Interfering alpha-streptococci as a protection against recurrent streptococcal tonsillitis in children. AB - Recurrent streptococcal tonsillitis/pharyngitis is a great problem, especially in certain epidemiological situations. Patients treated with antibiotics often have a disturbed normal throat flora and may lack, e.g., alpha-streptococci known in vitro to have an interfering activity against group A streptococci. Thirty-one patients with recurrent streptococcal tonsillitis were given antibiotics for 10 days. At the end of this treatment they were sprayed in their mouths with four selected alpha-streptococcal strains known to have strong growth inhibiting activity in vitro against most beta-streptococci group A. The follow-up period after this colonization was 3 months. After alpha-streptococcal treatment, none of the patients attracted a new tonsillitis during the follow-up period while 8% of the controls had a second tonsillitis. Treatment of streptococcal tonsillitis/pharyngitis with antibiotics followed by recolonization with alpha streptococci seems to hinder further recurrences. PMID- 8436459 TI - Tonsillectomy and adenoidectomy pain reduction by local bupivacaine infiltration in children. AB - Experimental data in humans and animals suggest that during surgery, pain impulses enter the CNS creating a hyperexcitable state in spite of general anesthesia. In a prospective double blind study, pain levels in 22 children undergoing tonsillectomy and adenoidectomy under general anesthesia were compared from day of surgery to Day 10. Patients received pre-incisional infiltration with either bupivacaine (A) or saline (B). Subjective pain was assessed by visual analog scale, and objective pain by deglutition time (100 ml). Subjective constant pain was less (P < 0.05) in group (A) on Day 1: 16 (A) vs. 59 (B) and Day 5: 4 (A) vs. 45 (B). We conclude that local nerve blockade by bupivacaine reduces short- and long-term pain in children undergoing tonsillectomy and adenoidectomy in the presence of general anesthesia. PMID- 8436460 TI - Childhood epiglottitis in recent years. AB - Fifty-five cases of acute epiglottitis were diagnosed and treated at the Children's Hospital of Philadelphia between 1985 and 1991. To evaluate the changing patterns of the disease over recent years, we compared the current results with those obtained from an earlier study reported at our institution in 1979. The overall annual incidence was higher in recent years than in the earlier study, with a sharp decline in new cases over the last two years. Thirty-six percent of the Hemophilus influenzae type B (HIB) infections were ampicillin resistant in recent years, while no resistance had been found in the past. Twenty seven percent of the cases were vaccine failures, all before 1990. Endotracheal intubation was the sole method for upper airway maintenance, while in the past 31% of the children underwent a tracheotomy. No mortality or long-term complications were found in either study. PMID- 8436461 TI - Reconstruction of the growing cricoid with a composite graft of demineralized bovine bone and autogenous perichondrium; a comparative study in rabbits. AB - In growing rabbits, the feasibility of a new type of composite graft for the reconstruction of defects in the cricoid ring is studied. This graft consists of Demineralized Bovine Bone matrix (DBBM) enfolded in a perichondrial flap. The cartilage formed in the DBBM by cells, derived from the perichondrium, is demonstrated to provide a valuable substitute for resected parts of the cricoid. A specific feature of this reconstruction is that it allows further growth and does not result in a secondary stenosis during later development. PMID- 8436462 TI - Voice problems after pediatric laryngotracheal reconstruction: videolaryngostroboscopic, acoustic, and perceptual assessment. AB - Children with laryngotracheal stenosis undergo laryngotracheal reconstruction (LTR) to permit tracheostomy decannulation. We conducted voice assessments of 8 pediatric LTR patients with voice problems. Perceptual ratings and acoustic measures were taken in 5 patients and videolaryngoscopy/laryngostroboscopy was conducted in all 8. Results of perceptual evaluation were abnormal for hoarseness, breathiness and pitch. Acoustic analysis revealed a markedly decreased fundamental frequency of phonation, diminished frequency range, decreased vocal intensity, and shortened maximum phonation time. Videolaryngostroboscopic findings are summarized as follows: 2 patients had severe glottal insufficiency, 3 patients had vocal fold asymmetry in stiffness and position, and 3 patients demonstrated phonation using supraglottal structures. Use of the stroboscope contributed to diagnosis in 3 of 8 patients. Reverse (inhalatory) phonation was observed in three patients. Concomitant articulation problems were exhibited frequently. Sentence production was shortened by the decreased phonatory duration. When coupled with the abnormal voice quality, speech intelligibility was significantly affected. Voice problems following decannulation were observed to persist as a long-term difficulty in some LTR patients. PMID- 8436463 TI - A middle ear teratoma causing acute airway obstruction. AB - A rare benign teratoma of the middle ear, eustachian tube and nasopharynx presenting in an 8-month-old infant, is reported. The true nature of the tumour was not appreciated until after partial surgical resection from the middle ear. This procedure was complicated 3 days later by life-threatening airway obstruction, caused by the tumour slipping from the eustachian tube and obstructing the larynx. This unusual presentation and the pathology of the teratoma are discussed. The case demonstrates the importance of nasopharyngeal examination where middle ear lesions distort the eustachian tube. PMID- 8436464 TI - Prophylaxis for recurrent acute otitis media: a Brazilian study. AB - We enrolled 60 children with recurrent acute otitis media (AOM) in a study of the effectiveness of antimicrobial prophylaxis. All children were entered into the study following an acute episode of infection treated with amoxicillin (AMX) for 10 days. Following therapy, the children were re-examined, and then randomly assigned to receive either trimethoprim-sulfamethoxazole (TMP-SMX), amoxicillin (AMX) or a placebo (PLA). Twenty children were included in each group. Each drug was administered once a day at bedtime, at 1/3 the therapeutic dose, for 3 months. Children were re-evaluated with pneumootoscopy during episodes of acute illness and with pneumootoscopy and impedance tympanometry (TYMP) at monthly intervals. We observed a significantly increased rate of recurrent AOM in children receiving placebo compared with those who received antibiotics (50% vs. 17% P < 0.005). Both prophylactic antibiotics were equally effective in preventing recurrent AOM (recurrence rate 20% TMP-SMX, 15% AMX). We also observed that recurrences in children receiving placebo occurred earlier in the study period than in those receiving antibiotics. These results suggest that antimicrobial prophylaxis in children with recurrent acute otitis media is effective in reducing subsequent disease. The similar efficacy of both antibiotics tested suggests that the less expensive agent should be used. PMID- 8436465 TI - Juvenile fibromatosis: hormonal receptors. AB - Aggressive juvenile fibromatosis, though allegedly a benign process, is as frustrating to manage as it is perplexing to comprehend. The treatment is primarily surgical, with chemotherapy and radiation therapy recently finding support as adjuncts in selected circumstances. Though there is no agreement regarding the etiology of fibromatosis, many have suspected hormonal or traumatic influences. There has been historical, clinical and experimental data demonstrating that fibromatosis seems to be under the influence of estrogen. There have also been anecdotal reports that this tumor has regressed with the use of tamoxifen. To our knowledge, no one has tested these tissues for the presence of estrogen/progesterone receptors. Recently, over a short period of time, we at Children's Memorial Hospital, Chicago, have treated four youngsters with this disorder. All operative specimens were submitted for estrogen and progesterone assays. Although these cases were indistinguishable on histologic examination, two of the four exhibited the presence of estrogen/progesterone receptors. We propose, that from these observations, there potentially may be derived a histochemical classification based upon the presence or absence of estrogen/progesterone receptors. This would serve as an added reference in the definition and treatment of this disease. Should hormonal receptors be present, agents such as tamoxifen conceivably could be employed as part of a post operative maintenance regimen similar to those protocols applied in the management of hormonally responsive breast cancer. PMID- 8436466 TI - Klippel-Feil syndrome with congenital conductive deafness: report of a case and review of literature. AB - Klippel-Feil syndrome is a clinical triad consisting of short neck, decreased head mobility, and low occipital hairline. Additional deformities of the musculoskeletal and the neural system may also be present. Otological defects occur in about one third of these patients. They are seen either unilaterally or bilaterally and accompanied by deafness which may be perceptive, or mixed, or rarely conductive in type. They are caused either by dysplasia of the labyrinth and/or internal auditory canal, or by the middle and the outer ear. We present a report of a case of Klippel-Feil syndrome with congenital conductive deafness. Detailed radiological investigations failed to show any malformations of the middle ear. At operations, thick glue was removed from the middle ear cavities, and dehiscent fallopian canals and bulging of the facial nerve in the tympanic segment were seen. One year postoperatively, audiometry showed a hearing gain of only 20 dB on both sides. Review of the literature shows that there is a trend among the contemporary otologic surgeons to undertake curative surgery whenever possible, so as to improve the hearing, despite isolated reports of various difficulties and complications of curative surgery. PMID- 8436467 TI - Neonatal respiratory distress: sequela of bilateral nasolacrimal duct obstruction. AB - Neonatal respiratory distress is a commonly seen entity whose causes are legion. Nasal obstruction secondary to intranasal masses is significant because neonates are obligate nasal breathers. Congenital nasolacrimal duct obstruction (NLDO) causing respiratory distress is an extremely rare event since most cases of NLDO do not compromise the nasal airway. We report two cases of neonatal respiratory distress secondary to bilateral NLDO with cystic mucocele formation and intranasal extension; only two similar cases have been previously described. Pertinent embryology and anatomy are reviewed as is a brief discussion of congenital NLDO. MRI and a nasal endoscopic photograph are provided demonstrating the nasolacrimal and nasal pathology. Treatment strategies are outlined. Consideration of nasolacrimal duct pathology in the differential diagnosis of neonatal respiratory distress and nasal obstruction is stressed. PMID- 8436468 TI - Aneurysmal bone cyst of the maxilla: case report and review of the literature. AB - Aneurysmal bone cyst (ABC) is a rare benign lesion of the head and neck. A case of an ABC in a 12-year-old female is presented, the twentieth reported such case in the maxilla. Literature review shows ABC are common in the long bones; only 2% are in the head and neck. Of the 77 lesions in the head and neck found in the literature, 31 (40%) are in the mandible, 20 (26%) are in the maxilla (including this case) and the remainder mainly in the skull. Current recommended treatment is curettage with enucleation first if technically possible. PMID- 8436469 TI - Diplophonia in a neonate. AB - Diplophonia has never been described in a neonate. An unusual case, then, of diplophonia in a neonate is described here. There is a description of the acoustic characteristics of this infant's cry and a discussion of their significance. This contributes to a review of the differential diagnosis of diplophonia. Moreover, this case further shows the essential relation between laryngoscopic findings and acoustical data. PMID- 8436470 TI - Tongue hypoplasia in a newborn. AB - Congenital anomalies of the tongue are uncommon. Since de Jussieu first described lingual hypoplasia in 1719, fewer than 50 cases have been described. These are usually in association with the hypoglossia-hypodactylia syndrome. We present a case of a newborn with absent anterior tongue, a rudimentary posterior remnant and associated micrognathia. Embryology and theories of pathogenesis are discussed. PMID- 8436471 TI - Laryngomalacia and intra-neural striated muscle in an infant with the Freeman Sheldon syndrome. AB - Striated muscle cells within peripheral nerve trunks, a very rare dishistogenetic lesion, was found in the arytenoid submucosa of a ten and a half week old afroamerican male with the Freeman-Sheldon syndrome (craniocarpotarsal dysplasia) who presented with obstructive apnea. Laryngomalacia was confirmed endoscopically. Supraglottoplasty offered temporary relief of the obstruction. Our histopathological observation is puzzling and perhaps adds a new dimension to the appropriateness of 'dysplasia'. It remains to be seen whether the neuromuscular lesion is a coincidental finding, a mere curiosity or bears any clinical significance. PMID- 8436472 TI - Jugular bulb phlebectasia. AB - Phlebectasia of the internal jugular vein (IJV) is a rare venous anomaly that usually presents in young children as a soft cystic swelling in the neck and represents a pathologically enlarged vein. We present a case of jugular bulb phlebectasia in a 4-year-old boy. He presented with a blue pulsatile swelling arising from the floor of the left middle ear cleft. The venous phase of digital subtraction vertebral arteriography (DSVA) and computerised axial tomography (CT) with contrast confirmed a diagnosis of phlebectasia of the lateral sinus and proximal part of the left IJV, with a complete bony defect in the floor of the middle ear. The child did not have any neck symptoms or signs. No active treatment was required. To our knowledge, this is the first case of jugular bulb phlebectasia presenting in the middle ear. PMID- 8436473 TI - Silent reading and secretory otitis media in school children. AB - In an unselected cohort of 366 8-year-old children, the relationship between secretory otitis media and reading achievement was investigated. The children underwent 10 impedance audiometries and 5 pure tone audiometries during their first year at school. At the beginning of the second grade they all had a Silent Reading Word Test (OS-400). The background parameters were recorded by an interview with one of the parents. There was a significant but small correlation between type B tympanograms in the first grade and silent word reading. No association between silent reading score and otological history or pure tone screening was found. In a stepwise multiple regression model, 37% of the variance could be 'explained' by the included variables. The 'classroom factor' could 'explain' about 17% of the variance, followed by phonology at the start of school (6%), gender (5%), social group of the mother (4%), type B tympanogram (2%), absence from school (2%) and allergy (1%). PMID- 8436474 TI - Ameloblastic fibrosarcoma. AB - A case of an ameloblastic fibrosarcoma in the mandible is described. The primary tumor was seen in a 5-year-old child. In spite of repeated surgical interventions, the tumor recurred three times within a one and a half year period, but not metastases have been observed. The difficulties in arriving at a correct diagnosis for this rare tumor involving the mandible are discussed. The treatment of choice seems to be radical surgery. PMID- 8436475 TI - Inflammatory pseudotumor: an unusual cause of recurrent pneumonia in childhood. AB - Recurrent pneumonia in the pediatric population may be caused by a variety of etiologies. If persistent, a referral to an otolaryngologist is often made for assistance in the diagnosis and treatment of such a problem. Bronchoscopy is frequently necessary to establish a diagnosis. Although foreign bodies, as well as infectious processes, are most often encountered, benign and malignant tumors must be considered. We report a case of a 10-year-old male who was found to have an inflammatory pseudotumor which presented with recurrent pneumonia. The importance of suspecting tumors, and including them in the differential diagnosis is emphasized. PMID- 8436476 TI - Submandibular hemangioma as the initial manifestation of Kasabach-Merritt syndrome. AB - Kasabach-Merritt syndrome (thrombocytopenia, consumption coagulopathy and occasional hemolysis) is an infrequent but often fatal complication of rapidly growing hemangiomas in infants. We describe a 1-month-old infant with a huge hemangioma involving the left submandibular region associated with a severe consumptive coagulopathy, who was successfully treated with transfusion of blood products, prednisone and radiation therapy. It is stressed that pediatric otorhinolaryngologists should always be aware of the lethal status of this condition in infants. PMID- 8436477 TI - Surgical drainage of subperiosteal abscess of the orbit (SPA) PMID- 8436478 TI - Recurrent otitis media: genetic immunoglobulin markers in children and their parents. PMID- 8436479 TI - The vestibulo-ocular reflex in pupils at a Dutch school for the hearing impaired; findings relating to acquired causes. AB - The vestibulo-ocular reflex was evaluated with caloric tests and velocity step (VS) tests in 121 pupils at a school for the hearing-impaired. Vestibular impairment was found in a total of 50 pupils (41%). It was found in 17 out of the 33 (52%) pupils with acquired causes of hearing impairment and significantly more often in pupils with a pure tone hearing threshold of more than 90 dB than in those with a lower threshold. In the group with prenatal causes, 5 out of 8 rubella cases showed vestibular impairment. Four of these cases had impaired VS responses and normal caloric responses. The high proportion of vestibular impairment in the group with postnatal causes was due to 5 cases with meningitis, all of whom showed caloric weakness. Kernicterus was significantly associated with vestibular hyperreactivity (5 cases out of 7), presumably due to a central dysfunction. PMID- 8436480 TI - Reflectometric screening for otitis media: inconsistencies in a sample of Australian aboriginal children. AB - This paper evaluates reflectometry, or acoustic otoscopy, as an objective test for the mobility of intact tympanic membranes in Australian Aboriginal children, who are a population at high risk for otitis media. Reflectometry, pneumotoscopy and tympanometry were compared in 395 ears in 198 Aboriginal children living in remote communities in Northern Australia. A strong interaction was found between pneumotoscopy and tympanometry (P < 0.001), there was some interaction between pneumotoscopy and reflectometry (breakpoint 5.0) (P < 0.05) and there was no significant interaction between reflectometry and tympanometry. Results showed that intra-observer and inter-observer agreement for measures of reflectivity were 0.87 and 0.83, respectively. Unexpected differences between reflectivity measures for right (mean 5.4 units) and left (mean 4.9 units) ears and for different test locations were attributed to procedural artifact or training effects. It was concluded that, despite its practical advantages, reflectometry cannot be recommended as a screening tool for tympanic membrane (TM) immobility in this population. PMID- 8436481 TI - Transient evoked otoacoustic emissions: clinical applications and technical considerations. AB - Otoacoustic emissions are defined as sound energy emitted by the cochlea. They are believed to be generated by the outer hair cells of the Organ of Corti. Several types of evoked otoacoustic emissions have been described. At present, transient-evoked otoacoustic emissions (TEOAEs) equipment is readily available commercially for clinical purposes. This paper describes our early experience with this equipment from a clinician's perspective. It reviews some of the technical problems we have encountered and their solutions. It also presents selected clinical examples where TEOAEs were particularly helpful in the clinical setting, thus illustrating the potential usefulness of this new clinical tool. PMID- 8436482 TI - Evoked otoacoustic emissions and pure tone threshold audiometry in patients receiving cisplatinum therapy. AB - Eight children and young adults with cancer were evaluated serially using pure tone audiometry as well as registration of click-evoked otoacoustic emissions (EOAE) 1 day prior to therapy as well as after various numbers of doses of cisplatinum. A reduction of EOAE-amplitudes following cisplatinum therapy was observed in all patients. This reduction tended to recover after the end of cisplatinum administration. Since EOAE are believed to result from cochlear bio mechanical processes, the reduced emissions are interpreted as signs of cochlear dysfunction. We conclude, that EOAE testing may be a simple, non-invasive method that may detect early, transient functional impairment of hearing due to ototoxic agents such as cisplatinum, even in children. Further controlled trials are needed. PMID- 8436483 TI - External ear resonance as a screening technique in children with otitis media with effusion. AB - External ear resonance can be quickly and accurately measured using real ear insertion gain equipment. It has been previously shown that external ear resonance characteristics are often altered by the presence of middle ear fluid. The external ear resonance characteristics of 84 children with a history of chronic middle ear disorder were determined. Results were compared to other audiological data and otological findings recorded during surgery. External ear resonance peak amplitude was significantly correlated with the presence or absence of middle ear fluid. It was found that peak amplitude of > or = 24 dB was associated with only 15% of dry ears and peak amplitude of < or = 22 dB associated with 79% of ears without fluid. The use of external ear resonance measures as a potential screening procedure is discussed. PMID- 8436484 TI - Active immunisation and resistance to experimental acute pneumococcal otitis media. AB - The middle ear mucosal system and the humoral systemic immune factors are the two immunological systems whose involvement in the defence against acute otitis media (AOM) have been most intensively studied. However, their respective importance and their mutual influence is not clear. In the present study, a rat model for pneumococcal AOM was used to further elucidate the involvement of systemic immunity in protection against pneumococcal AOM. Six groups of male Sprague Dawley rats were immunised with pneumococcal vaccine (PneumovaxRN) or live pneumococci (type 3) via one of three different routes: intraperitoneally, into the gastrointestinal tract (GIT) or into the right middle ear. A subsequent middle ear challenge (re-challenge in one group) with the same pneumococcal strain was performed after 4 days to 8 weeks in the different groups. Systemic immunity was found to be triggered, not only by systemic immunisation, but also by antigenic stimulation of the mucosa in the middle ear and in the GIT. In all groups but that immunised in the GIT, no new peak of specific IgG antibody response was demonstrated in serum after middle ear challenge/re-challenge. In contrast, half of the rats immunised in the GIT showed such a response not only after the inoculation into the GIT but also after a later performed middle ear challenge. Though a faster resolution of pus from the middle ear was observed in rats from all but one group, a significant reduction in the number of rats who developed AOM occurred exclusively among those rats that had previously manifested serological response to immunisation in the GIT. PMID- 8436485 TI - Surely the Wizard will help us, Toto? Implementing the Patient Self-Determination Act. PMID- 8436486 TI - The Patient Self-determination Act. An early look at implementation. PMID- 8436487 TI - Bioethics education. Expanding the circle of participants. AB - Bioethics education now takes place outside universities as well as within them. How should clinicians, ethics committee members, and policymakers be taught the ethics they need, and how may their progress best be evaluated? PMID- 8436488 TI - The voluble brother-in-law. PMID- 8436489 TI - Even in defeat, Proposition 161 sounds a warning. PMID- 8436490 TI - Is there a right to die? AB - To speak of rights in the very troubling matter of medically managed death is ill suited both to sound personal decisionmaking and to sensible public policy. There is no firm philosophical or legal argument for a "right to die." PMID- 8436491 TI - Not my problem. PMID- 8436492 TI - Less sympathy. PMID- 8436493 TI - Who's to choose? Surrogate decisionmaking in New York State. AB - The problem of finding appropriate decisionmakers for incapacitated patients continues to beleaguer caregivers. In New York state, a specially appointed task force has recently examined this issue and made some novel recommendations. PMID- 8436494 TI - Efficacy of meclofenamate sodium versus placebo in headache and craniofacial pain. AB - Twenty patients were enrolled in a double-blind, placebo-controlled crossover study of meclofenamate sodium in headache and craniofacial pain. There were four observation periods of 15 days each: Period 1 was a wash-out period. In period 2, subjects were randomly assigned to a 15-day regimen of taking two capsules a day of 100mg meclofenamate sodium (group 1) or placebo (group 2). In period 3, group 1 was switched to placebo and group 2 to meclofenamate sodium for the next 15 days. Lastly, the patients took no medication for a further 15 days (period 4). A thermographic record of the craniofacial and neck areas was taken at the end of periods 1 and 4. A record of the pressure threshold and tissue compliance at different sites of the craniofacial, neck and shoulder areas was taken at the end of each period. During the trial, number and duration of painful events were recorded daily by the patients, and the level of pain evaluated on a visual analog scale. Mean data were analyzed for significant difference by ANOVA and paired t-test. During the meclofenamate sodium period, there was a significant decrease of days with painful events compared to the wash-out period in group 1 and compared to the placebo period in group 2. In the majority of patients, the meclofenamate sodium period scored lowest or second-lowest after the follow-up period in mean pain intensity. Data for pressure threshold, although not significant, were indicative of a possible increase during and after intake of meclofenamate sodium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8436495 TI - Impact of migraine in the United States: data from the National Health Interview Survey. AB - Data from the 1989 National Health Interview Survey concerning migraine occurrence and impairment were analyzed to assess the impact of migraine on the US population. About four of every one hundred persons in the United States were found to have migraine, accounting for nearly 10 million individuals. Migraine was most prevalent in those aged 25 to 44 years and was about 2.5 times more frequent in females than males. Migraine was most common in whites (85%) and those with low household income. In women, migraine prevalence increased with the level of education. About 10% of migrainous children missed at least one day of school over a two-week period due to migraine; nearly 1% missed four days. Migraineurs were bedridden for about three million days per month and had an estimated 74.2 million days per year of restricted activity due to migraine. The potential cost of lost productivity was estimated at $1.4 billion per year for the estimated 6,196,378 migraineurs who worked outside the home. It is difficult to derive similar estimates for costs of lost productivity in housewives; however, housewives experienced an estimated 38 million days per year of restricted activity. Eighty-five percent of females and 77% of males reported a physician visit at some point for their migraine. Migraine is a relatively common disease whose social and financial impact has been poorly understood. PMID- 8436496 TI - Wolff Award 1992. Exteroceptive suppression of temporalis muscle activity in patients with chronic headache and in normal volunteers: methodology, clinical and pathophysiological relevance. AB - Exteroceptive suppression of temporalis muscle activity was studied in patients with chronic headache and in healthy controls. Among different methods of recording, averaging 10 full-wave rectified EMG responses produces results with acceptable variability and discomfort. The late temporalis exteroceptive suppression period (ES2) is reduced on average in patients with chronic tension type headache; this finding has been reproduced by several independent laboratories. Mean duration of temporalis ES2 is also diminished, but to a lesser degree, in daily drug abuse headache and, as shown by others, in episodic tension type headache. It is normal in migraine between attacks, cluster headache and various types of symptomatic headaches. Temporalis ES2 may be decreased in untreated patients with major depression. In healthy volunteers, temporalis ES2 duration is reduced by a short-lasting painful stimulus to peripheral limbs after a delay of 50 to 60 ms, and by a sub-motor threshold electromagnetic stimulation to the contralateral cerebral cortex after a delay of 20 to 30 ms. In contrast, long-lasting trains of peripheral painful stimuli have no effect. Various pharmacological agents are able to modify temporalis ES2. Its duration is increased by 5-HT antagonists, but decreased by 5-HT uptake blockers. Pharmacological effects may differ between controls and patients. Considering these results and available data on the anatomo-functional organization of masticatory reflexes, we postulate that temporalis ES2 is a marker of the excitability of interneuronal nets in the ponto-medullary reticular formation. In chronic tension-type headache, excitability of these interneurons is decreased because of inadequate control by the serotonergic raphe magnus nucleus and the periaqueductal gray matter. Dysfunctioning of the latter structures might be caused by abnormal limbic inputs to the brain stem. Some steps of this pathophysiological hypothesis can be verified by modern neurophysiological techniques. PMID- 8436497 TI - A placebo-controlled crossover trial using trazodone in pediatric migraine. AB - An 8-month, double-blind, placebo-controlled cross-over trial was carried out on the use of trazodone in pediatric migraine prophylaxis. It involved 40 patients aged 7 to 18 years old and suffering from migraine without aura, randomly divided into 2 groups. After a 4-week run-in period, Group A received oral trazodone (1 mg/kg a day divided into 3 doses) for 12 weeks, while Group B received a placebo. After a further 4-week washout period, Group A was given the placebo and Group B was treated with trazodone for a further 12 weeks. The trial was completed by 35 patients, the number of drop-outs being comparable in the two groups. During the first treatment period, both the frequency and the duration of the migraine episodes were significantly reduced in both groups. During the second, a significant further improvement in both parameters was only observed in Group B. No side-effects were observed at any time. Our results showed that, like other antidepressants, trazodone is a valid prophylactic agent for juvenile migraine. PMID- 8436498 TI - Head band for migraine headache relief. AB - Application of an ice pack and local scalp pressure are the most commonly used non-pharmacological methods for temporary relief of migraine headache pain. An elastic band secured around the head with Velcro and firm rubber discs inserted under the band was used to apply local pressure over the area of maximum pain in 25 patients with migraine headache. Three headaches were studied in each patient. Two patients dropped out because of local tenderness which prevented them from using the band. The 23 remaining patients used the band in a total of 69 headaches. Pain relief was monitored for 30 minutes at 10 minute intervals. Sixty headaches (87%) were relieved. Nine headaches (13%) were not improved. Sixty seven percent of those who improved (40 headaches) had relief of over 80%, twenty five percent (15 headaches) improved between 50-60% and eight percent (5 headaches) had less than 50% improvement. Pain severity steadily increased when the band was released. Temporary relief of pain from mechanical compression of the scalp supports the possibility that at least part of the pain in migraine headache originates from dilated blood vessels in the scalp. PMID- 8436499 TI - Side alternation of pain in hemicrania continua. PMID- 8436500 TI - Migraine occurring as sequela of electroconvulsive therapy. PMID- 8436501 TI - [The dermo-epidermal juncture. Recent aspects of pathophysiology]. AB - The dermo-epidermal junction anchors the epidermis with the dermis but separates simultaneously these two layers. The complex structure of this zone is important for the coherence of the skin and for resistance against shearing forces. Abnormalities of the zone that result form e.g. binding of immune deposits or genetic defects, can lead to dermo-epidermal splitting and blister formation. Recent morphologic, biochemical and molecular biological investigations have generated new information that allows faster and easier diagnosis of bullous diseases. Investigations of patients with hereditary blistering disorders have revealed some of the mechanisms that underlie the different forms of epidermolysis bullosa. PMID- 8436502 TI - [In vivo and in vitro detection of borrelia infection in morphea-like skin changes with negative Borrelia serology]. AB - No decision has been made yet as to whether or not the origin of the circumscribed scleroderma (morphea) is spirochetal. We describe a morphea-like skin lesion that developed after a tick bite 10 years ago. The histological investigation showed sclerodermal characteristics and necrobiosis lipoidica of the granulomatous type as well. No antibodies directed against Borrelia burgdorferi could be detected absorbance by a flagellin ELISA or by Western blot analysis. The VDRL, TPHA and FTA absorbance test, Warthin-Starry staining, and cultivation of Borrelia from skin biopsies were negative. The application of a nested polymerase chain reaction (PCR), relying on a combination of flagellin gene-specific primers, demonstrated for the first time the presence of Borrelia DNA in a morphealike skin lesion. Immunohistological examination of the skin by a monoclonal antibody directed against flagellin was positive. Furthermore, in vitro GM-CSF secretion and lymphocyte proliferation upon stimulation with Borrelia-antigen was elevated and decreased significantly after 3 weeks of treatment with tetracyclines. In this case PCR analysis, immunohistochemistry and cellular immune response confirmed an infection with Borrelia, although no serum antibodies against spirochetal antigens could be detected. PMID- 8436503 TI - [Encephalocraniocutaneous lipomatosis. A non-hereditary mosaic phenotype]. AB - Encephalocraniocutaneous lipomatosis is a distinct neurocutaneous syndrome characterized by an extensive fatty tissue nevus of the scalp, protuberances of the cranial bones, lipodermoid of the conjunctiva, multiple intercranial lipomas, and porencephaly. A further case of this multisystem birth defect is reported. The patchy arrangement of lesions that is usually unilateral suggests a mosaic phenotype. The clinical criteria to distinguish this disorder from other mosaic neurocutaneous phenotypes, such as Schimmelpenning syndrome, Proteus syndrome, or Delleman syndrome, are outlined. To explain the origin of this nonhereditary genodermatosis, the concept of a lethal autosomal mutation that survives in a mosaic state is proposed. PMID- 8436504 TI - [Analysis of 1983-1991 Leipzig University Dermatology Clinic observed cases of syphilis]. AB - A total of 1380 patients with syphilis were diagnosed and treated from January 1983 to December 1991 at the Department of Dermatology and Venereology at Leipzig University in West Saxon, Federal Republic of Germany where the population is 1.4 million. The incidence of syphilis increased gradually from 1983 to 1989 and then decreased again. The number of recent cases of syphilis was almost twice as high as latent syphilis cases (63:37%). The vast majority of cases suffered from early syphilis. In almost half the source of infection was casual contacts (44%); in one-third it was a stable partners (30%); about 6% were homosexuals and about 4% were prostitutes. Among the primary syphilis cases multiple chancres were seen in 16%. In 31% of cases, the ulcus durum was extragenital. Among the secondary syphilis cases macular and maculopapular exanthema were the commonest features (51%), followed by palmoplantar syphilis (5%), condylomata lata (5%), angina specifica (3%) and papular exanthema (3%). However, in 30% of the cases multiple skin features were observed. Secondary syphilis with persistent chancres were seen in 12%. Five percent of the patients were suffering from the second to the fifth reinfection in their life, and again 5% of the syphilis cases were detected during pregnancy. Only two patients had an HIV infection, 10% suffered from gonorrhea and 10% from trichomoniasis, 12% from chlamydial infection, 4% from genital warts and 8% from herpes simplex genitalis at the same time. The therapy of choice was penicillin. In 0.3% an allergy to penicillin was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8436505 TI - [The Kobner phenomenon in Duhring dermatitis herpetiformis]. AB - We report on four female patients with confirmed dermatitis herpetiformis DH and Kobner phenomenon in identical localizations. All four had typical bilateral lesions in a band-like arrangement along the straps of their brassieres, and two patients also had additional lesions in other sites prone to pressure. Obviously, the Kobner phenomenon is not as rare in DH as would be expected in view of a single previous case report. PMID- 8436506 TI - [Acne necrotica (varioliformis). Necrotizing lymphocytic folliculitis]. AB - We report on a 32-year-old woman with chronic relapsing papular and papulopustular lesions in the area of the hairlines and on the scalp. The diagnosis of acne necrotica (varioliformis) was made on the basis of the typical clinical picture and the histopathology, which showed necrotizing lymphocytic folliculitis. This rare disease must be differentiated from other pustular diseases of the scalp. Acne necrotica has been known as an entity since the beginning of the last century. In recent literature, however, it has received little attention. PMID- 8436507 TI - [Hair casts in lichen ruber]. AB - We present a 59-year old male patient, who had small plant cylinders 1-2 mm in length adhering to the hair shafts and easily moved up and down along them. We found hair casts together with lichen ruber follicularis and pseudopelade of the Brocq type. The presence of hair casts is often misdiagnosed as pediculosis capitis, piedra alba or trichorrhexis nodosa. The case report and the literature are discussed. PMID- 8436508 TI - [Local lipohypertrophy in insulin treatment]. AB - Local lipoatrophy and lipohypertrophy at injection sites are well known side effects of treatment with insulin. Conditions favouring these local complications are created when repeated or continuous injections are given into the same areas. We report on a 27-year-old female patient who suffered from persistent local swellings after use of an external pump which continuously injected human insulin via indwelling cannulas. PMID- 8436509 TI - [Erosive lichen planus of the glans penis. Treatment with cyclosporin A]. AB - After suffering from chronic and steroid-resistant erosive lichen planus of the glans penis for 2 years, a 42-year-old patient presented to our Institute. The clinical picture was of an erythematous and erosive lesion, superficially covered with sero-fibrinous exudations. Lichen planus was diagnosed by clinical and histological examination. Control routine serum analysis and urinalysis gave normal results, and ciclosporin A was given at a dosage of 3 mg/kg daily. After 2 weeks of therapy, significant regression of erythema and infiltration was seen, so that the patient could be circumcised as planned. After leaving our Institute the patient continued the therapy with ciclosporin A and the monthly controls of kidney and liver function had shown no abnormalities during the 6-month follow-up that had elapsed up to the time of writing. PMID- 8436510 TI - [Hypogonadotrophic hypogonadism with pulsatile GnRH therapy]. AB - In idiopathic hypogonadotropic hypogonadism of men it is possible to normalize the endocrine and exocrine testicular function by pulsatile therapy with a GnRH pump. The long duration of the therapy can cause difficulties with compliance in young patients. PMID- 8436511 TI - [Therapy of verrucae vulgares in the immune suppressed patient]. PMID- 8436512 TI - [Clinical aspects and therapy of Bureau-Barriere syndrome. Observations of 17 cases with review of the literature]. AB - Bureau-Barriere syndrome can affect various organ systems. It is defined by the triad: painless ulcers at mechanically irritated and hyperkeratotic plantar areas of the feet, sensitive polyneuropathy of the lower legs and osteolysis in the forefoot area. The condition mainly affects middle-aged men suffering from alcoholism, liver disease, obesity or metabolic disorders such as diabetes mellitus. Successful treatment of the Bureau-Barriere syndrome requires an interdisciplinary approach. PMID- 8436513 TI - [Comment on the contribution by L. Weber: Yersinia exanthema]. AB - Lutz Weber has described Yersinia exanthema, a distinctive dermatological disorder characterized by three or all of the following signs: 1. A typical erythema-multiforme-like eruption, particularly on the neck, shoulders, and arms, 2. Erythema nodosum, 3. Conjunctivitis, particularly on the nasal side of the conjunctiva, 4. Arthralgia. The case presented here concerns a patient who satisfied all of the criteria for Yersinia exanthema and in whom no infection could be demonstrated. PMID- 8436514 TI - [Ludwig Nekam 1868-1957. A delayed obituary]. PMID- 8436515 TI - [Food intolerance. II]. PMID- 8436516 TI - The influence of treatment time on outcome for squamous cell cancer of the uterine cervix treated with radiation: a patterns-of-care study. AB - PURPOSE: To analyze the effect of total treatment time on infield pelvic control and survival for squamous cell carcinoma of the uterine cervix using the combined 1973 and 1978 Patterns of Care (PCS) data base. METHODS AND MATERIALS: Eight hundred thirty-seven evaluable patients were analyzed for the effect of total treatment time on outcome. The Kaplan-Meier method was used to estimate time-to outcome annual rates. Comparisons of time to failure were performed with the log rank test. Multivariate analysis was performed using the Cox regression analysis. RESULTS: A highly significant decrease in survival (p = .0001) and pelvic control (p = .0001) was demonstrated as the total treatment time was increased from < 6, 6 to 7.9, 8 to 9.9, and 10+ weeks. Stage III accounted for the majority of the adverse effect from the prolongation of total treatment time. Multivariate analysis of total treatment time in addition to previously reported significant pretreatment and treatment factors from the PCS data base revealed three independent factors for infield recurrence, namely Stage I versus II versus III (p = .0001), total treatment time < 6 versus 6 to 7.9 versus 8 to 9.9 versus 10+ weeks (p = .003), and age > 50 versus < or = 50 years (p = .01). When the analysis was performed by stage to evaluate the effect of overall treatment time with respect to the extent of pelvic disease as defined by PCS, total treatment time continued to be an independent prognosticator for infield pelvic control (p = .01) and survival (p = .02) for Stage III but not Stages I and II. CONCLUSION: This study demonstrates a significant adverse effect on survival and pelvic control with prolongation of the total radiation treatment time for Stage III squamous cell cancer of the uterine cervix in multivariate analysis. In the future design of clinical trials, limitations on total treatment time should be rigorously controlled, and the effect of variations in this important factor by altered fractionation schemes should be studied. PMID- 8436517 TI - Phase III trial comparing two low dose rates in brachytherapy of cervix carcinoma: report at two years. AB - This Phase III randomized trial examined the effect of two low dose rates (0.73 or 0.38 Gy.h-1) on the local control, survival, relapse-free survival, complications, and secondary effects in the treatment of cervical cancers. A total of 204 Stage Ib or II cervical carcinoma patients were included between January 1985 and September 1988. Treatment consisted of uterovaginal 137Cs irradiation followed by surgery. The two groups were similar for age, tumor stage and medical or surgical history. Their brachytherapy parameters were also similar (60 Gy pear dimensions, dose to critical organs, total kerma, etc....) There were no differences in the short-term effects or therapeutic outcome. However, overall complications and side effects observed after 6 months were significantly more frequent (p < 0.01) in the higher dose rate group. PMID- 8436518 TI - Radical radiation therapy for carcinoma of the vagina--impact of treatment modalities on outcome: Peter MacCallum Cancer Institute experience 1970-1990. AB - To determine the outcome of radical radiation therapy for carcinoma of the vagina, a retrospective analysis has been made of 103 patients referred with this diagnosis to the Peter MacCallum Cancer Institute from 1970 to 1989. Eighty-four patients were treated for cure, seventy-four patients with definitive radical radiotherapy and 10 patients with adjuvant post-operative radiotherapy. Results were analyzed from two eras--before and after 1985--reflecting changes in referral pattern, treatment policy, and outcome. Forty-eight patients were treated before 1985 (Stage I--24, Stage II--6, Stage III--15, Stage IV--3) and 36 patients after 1985 (Stage I--20, Stage II--3, Stage III--6, Stage IV--7). After 1985 more patients were treated with combined beam radiation and brachytherapy (23/36 vs. 16/48 prior to 1985). More extensive tumors were systematically implanted (Ir 192). (No implants before 1985; 15 implants and 8 intracavitary applications post 1985). Fewer were treated with external beam alone after 1985; 11/36 (31%) vs. 27/48 (55%) before 1985. A small number (7/84-8%) were treated with brachytherapy alone. Survival results were markedly improved after 1985 (22/36-61% vs 16/48-33%) due partly to the shorter period of follow-up, but due also to marked improvement in local control particularly in early stage disease. (1/23 vs. 12/30 recurrences in Stage I, II disease). Results indicate optimal results with radical radiation therapy occur only with adequate dose delivery best achieved with a judicious combination of external beam radiotherapy and brachytherapy. Interstitial implantation plays a crucial role. PMID- 8436519 TI - Radiotherapy after ovarian transposition: ovarian function and fertility preservation. AB - The outcome of ovarian function preservation and fertility after ovarian transposition was examined in women treated for cancer. Of 134 patients, 126 were treated with radiotherapy and 72 with chemotherapy. In a multivariate analysis, three factors appeared to be prognostic of ovarian castration: the age over 25, MOPP chemotherapy and a total dose to the ovaries higher than 5 Gy. The incidence of birth was lower in the general population but no abnormality was observed. PMID- 8436520 TI - Correlation of lymphangiography, computed tomography, and laparotomy in the staging of Hodgkin's disease. AB - PURPOSE: To determine the predictive value of lymphangiography and computed tomography of the abdomen and pelvis for infradiaphragmatic involvement of Hodgkin's disease. METHODS AND METHODS: We retrospectively reviewed the findings on 125 patients with Hodgkin's disease treated at the University of Florida who underwent lymphangiography and staging laparotomy; 33 patients also underwent computed tomography of the abdomen and pelvis. The positive predictive value and negative predictive value were calculated for both studies. RESULTS: The positive predictive value of lymphangiography for paraaortic or pelvic disease was 35%, while the negative predictive value was 95%. The positive predictive value of computed tomography of the abdomen and pelvis for paraaortic or pelvic disease was 20%; the negative predictive value was 93%. There was no advantage in predicting paraaortic or pelvic disease when both studies were obtained as compared to either study alone. For splenic disease, the positive predictive value of computed tomography was 43%; the negative predictive value was 77%. Of the patients with a positive lymphangiography, 57% were found at laparotomy to have either no abdominal disease or upper abdominal disease only, with or without minimal splenic disease, making them reasonable candidates for radiotherapy alone. Of the patients with a negative lymphangiogram, 14% were found at laparotomy to have either lower abdominal disease or extensive splenic disease, and so were not good candidates for radiotherapy alone. CONCLUSION: We recommend laparotomy for patients who may be candidates for radiotherapy alone or combined modality therapy with limited chemotherapy. PMID- 8436521 TI - Ewing's sarcoma: long-term follow-up in 49 patients treated from 1967 to 1989. AB - PURPOSE: Review of long-term results of therapy for Ewing's sarcoma in terms of survival, local tumor control, distant failure and complications rates. METHODS AND MATERIALS: Retrospective review of the records of patients with Ewing's sarcoma of bone and soft tissues treated at The Prince of Wales Children's and Prince of Wales Hospitals, Sydney, between 1967 and 1989 and followed-up to July 1991. RESULTS: There were 49 patients with median age 16 years (range 3-33 years) and average potential follow-up time 12.3 years (range 2-24 years). Forty patients presented with localized disease (three with regional lymph node involvement) and nine with distant metastases. Local therapy for the primary was by amputation in three patients, by resection and postoperative radiotherapy in five, and by definitive radiotherapy in 41 (median dose 50 Gy). Forty-four patients received adjuvant multi-agent chemotherapy. The overall actuarial survival rate was 33% (SE = 7%) at 5 years and 30% (SE = 7%) at 10, 15, and 20 years. The factors predictive of shorter survival were distant metastases at diagnosis (p = 0.036) and older age (p = 0.025). The actuarial local control rate for all 49 patients was 75% (SE = 8%) at 5, 10, 15, and 20 years. The only factor predictive of local failure was an inadequate target volume irradiated (p = 0.003). In 40 patients who presented with localized disease only, the actuarial rate of freedom from distant failure at 5 years was 44% (SE = 8%) and at 10, 15, and 20 years was 40% (SE = 8%). Seven patients experienced severe or fatal complications (defined as requiring investigation and treatment in hospital), namely stress fracture in two, fatal osteogenic sarcoma in one, fatal cardiotoxicity in one and severe hemorrhagic cystitis in three. The rate for severe or fatal complications at 5 years was 19% (SE = 8%), at 10 years was 29% (SE = 12%) and at 15 and 20 years was 53% (SE = 21%). CONCLUSION: Survival to 5 years appears to confer probable cure and one third of our patients have achieved this. Long-term follow-up also reveals that an increasing number of patients experience treatment-related complications, the majority of which, however, can be corrected. PMID- 8436522 TI - Probable causes of recurrence in patients with chordoma and chondrosarcoma of the base of skull and cervical spine. AB - PURPOSE: 141 patients with chordoma and chondrosarcoma of the base of skull and cervical spine were treated with proton and photon irradiation between 1980 and 1989. The local disease was controlled in 111 of these patients. This study reviews the 26 patients who have had their disease recur, and who have evaluable diagnostic studies to examine for probable causes of recurrence. METHODS AND MATERIALS: The histologies of the recurrent tumors were 21 non-chondroid chordomas, two chondroid chordomas, and three chondrosarcomas. The prescribed doses ranged from 67 Cobalt-Gray-Equivalent (CGE) to 72 CGE (average of 69 CGE). Doses to small regions of the tumor were deliberately reduced where they abutted certain normal tissues (brain stem, spinal cord, optic chiasm, and optic nerves) in order to keep these structures at acceptance dose levels. The first study, CT or MR scan, on which there was evidence of increase in tumor was carefully evaluated and that volume transferred to the CT scan on which the treatment plan had been developed. The 3D dose distribution in the region of recurrence was carefully analyzed and a judgement made as to the most probable cause of recurrence. RESULTS: Approximately one quarter (6 of 26) of the cases failed in the prescribed dose region. More than half (15 of 26) failed in regions where tumor dose was limited by normal tissue constraints. Approximately 10% of the patients recurred in the surgical pathway and 10% were judged to be marginal misses. CONCLUSIONS: Overall, 75% of the patients failed in regions receiving less than the prescribed dose. All tumors which failed in the high dose region had volume greater than 75 cc. Patients with cervical spine disease had a higher rate of recurrence (10 or 26) and larger tumors (average volume of 102 cc) than those with base of skull disease (16 of 115) with an average volume of 63 cc. PMID- 8436523 TI - Phase I study of debulking surgery and photodynamic therapy for disseminated intraperitoneal tumors. AB - PURPOSE: Phase I study designed to determine the maximum tolerated dose of intraoperative photodynamic therapy (PDT) at laparotomy/debulking surgery in patients with refractory or recurrent, disseminated intraperitoneal tumors. METHODS AND MATERIALS: Patients received dihematoporphyrin ethers (DHE) 1.5-2.5 mg/kg by i.v. injection prior to surgery. Patients resected to < or = 5 mm of residual disease underwent laser light delivery to all peritoneal surfaces. RESULTS: Fifty-four patients entered the study. Thirty-nine underwent resection and light delivery/PDT. PDT dose was escalated by increasing DHE from 1.5 to 2.5 mg/kg, shortening the interval between DHE injection and surgery from 72 to 48 hr, and increasing the light dose. Initially, 630 nm red light alone was used. In this group, PDT of 2.8-3.0 J/cm2 induced small bowel edema and resulted in 3 small bowel perforations after bowel resection or enterotomy. Further light dose escalation, however, was achieved by switching to less penetrating 514 nm green light to the bowel/mesentery. In later patients, whole peritoneal PDT was supplemented with boost doses of 10-15 J/cm2 red light or 5-7.5 J/cm2 green light to high risk areas. Small bowel complications were not seen after switching to less penetrating green light. Dose limiting toxicities occurred in 2 of 3 patients at the highest light dose of 5.0 J/cm2 green light with boost. These patients had pleural effusions that required thoracentesis and postoperative respiratory support for 7-9 days, while one had a gastric perforation. At potential follow-up times of 3.8-43.1 months (median 22.1 months), 30/39 patients are alive and 9/39 are free of disease. CONCLUSION: The maximum tolerated dose of intraoperative PDT following debulking surgery performed 48 hr after intravenous administration 2.5 mg/kg DHE is 3.75 J/cm2 of 514 nm green light to the entire peritoneal surface with boosts to 5.0-7.5 J/cm2 of 514 nm green light or 10-15 J/cm2 of 630 nm red light to sites of gross disease encountered at surgery. PMID- 8436524 TI - The tolerance of primate spinal cord to re-irradiation. AB - PURPOSE: This study was designed to assess the tolerance of the cervical spinal cord of rhesus monkeys to re-irradiation. This information is essential for treatment recommendations in previously irradiated patients. METHODS AND MATERIALS: Control animals received a single course of treatment to total doses of 70.4 Gy, 77.0 Gy, or 83.6 Gy in daily fractions of 2.2 Gy. Twelve asymptomatic animals that received 70.4 Gy were re-irradiated two years later to cumulative doses of 83.6, 92.4, or 101.2 Gy. Another group of 15 animals received 44 Gy and two years later were re-irradiated to cumulative doses of 83.6, 92.4, 101.2, or 110 Gy. The clinical endpoint was myeloparesis. A complete necropsy was performed in all animals when myeloparesis manifested or at the end of observation period. RESULTS: Only two of the 12 asymptomatic animals of the 70.4 Gy dose-response study group and two of the 15 animals that had received 44 Gy initially developed myelopathy within two years of re-irradiation. The ED50 value of the single course irradiation was 76.1 +/- 1.9 Gy, while the extrapolated ED50 for retreatment after 44 Gy was > or = 110 Gy. The lesions of the two symptomatic animals that received 70.4 Gy initially were mixtures of white matter and vascular lesions similar to those observed after single course irradiation. However, both symptomatic animals given 44 Gy initially had hemorrhagic infarcts in the white matter. CONCLUSION: The results of this study indicate that substantial recovery of occult injuries induced by the initial 44 Gy had occurred within two years. The difference between the types of lesions observed after a single course and re-irradiation suggests that vascular injury may recover less efficiently or at slower rate than white matter damage. The dependence of the extent of recovery on the initial dose and the time course of such recovery in primates are being investigated. PMID- 8436525 TI - Effect of glucose-mediated pH reduction and cyclophosphamide on oxygenation of transplanted rat tumors. AB - PURPOSE: Glucose-mediated reduction of tumor pH is under investigation as a means to improve the therapeutic index of anticancer agents. An improvement of glucose supply to tumors is, however, likely to influence various metabolic and pathophysiological parameters apart from pH which, in turn, could modulate H+ ion mediated effects. As a first step to identify changes in these parameter, we have investigated the effect of glucose-mediated pH reduction on oxygenation of malignant tissues either per se or in combination with a pH-sensitive drug, cyclophosphamide. METHODS AND MATERIALS: H+ ion and oxygen-sensitive semi microelectrodes were used to measure pH and pO2 in transplanted TV1A and AH13r rat tumors at normoglycemia and following high-dose intravenous glucose infusion. RESULTS: In both tumors analyzed, pH reduction was accompanied by a decrease in pO2. In TV1A tumors, for example, the mean (median) pO2 decreased from 8.2 mm Hg (3.7 mm Hg) to 3.9 mm Hg (1.7 mm Hg) at 2 hr and 2.9 mm Hg (1.9 mm Hg) at 24 hr, respectively, after raising the plasma glucose concentration to 25 +/- 2 mmol/l. At the same time points, the mean pH had declined from 6.89 to 6.29 and 6.24, respectively. The class of pO2 readings < 5 mm Hg increased from a pretreatment value of 65% to approximately 90% at 24 hr. In contrast, cyclophosphamide treatment resulted in improved oxygenation of AH13r tumors, an effect first observed at 24 hr after drug administration. When both modalities were combined, cyclophosphamide partly prevented the acidosis-associated decrease in oxygen partial pressure. CONCLUSION: The results of this study indicate that, within the context of the therapeutic approach used, cytotoxic agents should be employed which are more active against hypoxic than against well-oxygenated cells. In particular, glucose-mediated reduction of oxygen partial pressure in malignant tissues may be exploited to increase the fraction of hypoxic cells prior to administration of drugs activated in hypoxic cells by reductive metabolism (bioreductive agents). PMID- 8436526 TI - Comparison of radioimmunotherapy and external beam radiotherapy in colon cancer xenografts. AB - Radioimmunotherapy and external beam radiotherapy were compared in a nude mouse human colon cancer model. Radioimmunotherapy was delivered by intraperitoneal injection of 90Y-labeled anticarcinoembryonic antigen monoclonal antibody (anti CEA MAB). Single fraction external beam radiotherapy was delivered using a 60Co teletherapy unit. Control groups received saline, unlabeled anti-CEA monoclonal antibody and labeled nonspecific monoclonal antibody. Subcutaneous CEA-expressing LS174T human colon carcinoma tumors were measured over time. Tumor growth suppression was expressed as delay to reach 2g compared to saline controls. Unlabeled anti-CEA monoclonal antibody and labeled nonspecific monoclonal antibody had no effect. External beam radiotherapy of 300, 600, 1000 and 2000 cGy produced growth delays of 3, 12, 17, and 22 days, respectively. Radioimmunotherapy with 120 microCi, 175 microCi, and 225 microCi resulted in growth delays of 20, 34, and 36 days. Estimated absorbed tumor dose was 1750 cGy in the 120 microCi group. Similar comparisons were done with the more radioresistant WiDr human colon carcinoma cell line. External beam radiotherapy doses of 400, 800, 1200, and 1600 cGy resulted in growth delays of 6, 21, 36 and 48 days, respectively. Radioimmunotherapy of 120 microCi and 175 microCi resulted in growth delays of 9 and 19 days, respectively. The 120 microCi dose delivered an estimated absorbed tumor dose of 1080 cGy to WiDr tumors. In summary, for the radiosensitive LS174T line, radioimmunotherapy produced biologic effects that were comparable to a similar dose of single fraction external beam radiotherapy. For the more radioresistant WiDr tumor, radioimmunotherapy produced a biologic effect which was less than a similar dose of single fraction external beam radiotherapy. These studies suggest that a tumor's response to radioimmunotherapy relative to that of external beam radiotherapy is, in part, dependent on tumor radiosensitivity and repair capacity. PMID- 8436527 TI - Analysis of oxygen transport to tumor tissue by microvascular networks. AB - We present theoretical simulations of oxygen delivery to tumor tissues by networks of microvessels, based on in vivo observations of vascular geometry and blood flow in the tumor microcirculation. The aim of these studies is to investigate the impact of vascular geometry on the occurrence of tissue hypoxia. The observations were made in the tissue (thickness 200 microns) contained between two glass plates in a dorsal skin flap preparation in the rat. Mammary adenocarcinomas (R3230 AC) were introduced and allowed to grow, and networks of microvessels in the tumors were mapped, providing data on length, geometric orientation, diameter and blood velocity in each segment. Based on these data, simulations were made of a 1 mm x 1 mm region containing five unbranched vascular segments and a 0.25 mm x 0.35 mm region containing 22 segments. Generally, vessels were assumed to lie in the plane midway between the glass plates, at 100 microns depth. Flow rates in the vessels were based on measured velocities and diameters. The assumed rate of oxygen consumption in the tissue was varied over a range of values. Using a Green's function method, partial pressure of oxygen (PO2) was computed at each point in the tissue region. As oxygen consumption is increased, tissue PO2 falls, with hypoxia first appearing at points relatively distant from the nearest blood vessel. The width of the well-oxygenated region is comparable to that predicted by simpler analyses. Cumulative frequency distributions of tissue PO2 were compared with predictions of a Krogh-type model with the same vascular densities, and it was found that the latter approach, which assumes a uniform spacing of vessels, may underestimate the extent of the hypoxic tissue. Our estimates of the maximum consumption rate that can be sustained without tissue hypoxia were substantially lower than those obtained from the Krogh-type model. We conclude that the heterogeneous structure of tumor microcirculation can have a substantial effect on the occurrence of hypoxic micro regions. PMID- 8436528 TI - Hyperthermic enhancement of cell killing by five platinum complexes in human malignant melanoma cells grown as monolayer cultures and multicellular spheroids. AB - The cytotoxic properties of hyperthermia combined with cis-diammine dichroloplatinum(II) (CDDP), and recently developed platinum complexes, (Glycolato-O-O')diammineplatinum(II) (254-S), cis-1-1-cyclobutane-dicarboxylate (R)-2-methyl-1-4-butanediammine platinum(II) (NK-121), cis-diammine(1,1 cyclobutanedicarboxylato)platinum(II) (CBDCA), and (-)-R-[2 (aminomethyl)pyrrolodine](1,1- cyclobutanedicarboxylato)-platinum(II)monohydrate (DWA-2114R) were studied in vitro in monolayer cultures and multicellular spheroids of HMV-I human malignant melanoma cells. Hyperthermia at 44 degrees C for 30 min was applied during the latter part of 1 hr drug exposure. Cell survival was compared after drug treatments in cells exposed or not exposed to heat. Cytotoxicity was assessed by clonogenic assays. In exponentially growing monolayer cultures, marked hyperthermic sensitization was observed by each of the five platinum complexes studied. The dose modifying factors obtained were almost the same in these drugs. Unlike monolayer cells, the spheroids were appreciably different with regard to hyperthermic sensitization among platinum complexes. The order of the magnitude was as follows: CDDP, DWA-2114R, 254-S, CBDCA, and NK-121. In the low dose region, however, 254-S was the most thermally sensitized. These results suggest that the microenvironment factor within spheroids may significantly affect the cytotoxicity of platinum complexes combined with hyperthermia. On the basis of these findings using spheroids, CDDP, DWA2114R, and 254-S appear to be promising platinum complexes for use with hyperthermia clinically as far as hyperthermic sensitization is concerned. PMID- 8436529 TI - An original technique of brachytherapy for T1 T2 carcinomas of the mobile tongue. AB - Twenty-four patients with T1 or T2 (17 T1 N0, 7 T2 N0 not exceeding 3 cm) epidermoid carcinomas from the middle third of the mobile tongue benefit from brachytherapy with "cavaliers-legos" consisting of guide-gutters that are inserted in a rigid support (legos) and covered with a lead plate. Several advantages can be advocated with this technique: easy implantation even with local anaesthetic, no risk of bleeding, good parallelism between Iridium wires, protection of the mandible with the lead plate. Local control was achieved in 22/24 patients (92%). Four patients (16%) developed soft tissue necrosis but only one required surgical intervention and no mandibular necrosis was seen. PMID- 8436530 TI - Interactive use of on-line portal imaging in pelvic radiation. AB - We have evaluated a fluoroscopic on-line portal imaging system in routine clinical radiotherapy, involving the treatment of 566 pelvic fields on 13 patients. The image was typically generated by delivering a radiation dose of 6-8 cGy. Comparison between portal image and simulator film was done by eye and all visible errors were corrected before continuing irradiation. If possible, these corrections were performed from outside the treatment room by moving the patient couch by remote control or by changing collimator parameters. Adjustments were performed on 289/530 (54.5%) evaluable fields or 229/278 (82.4%) evaluable patient set-ups. The lateral couch position was most frequently adjusted (n = 254). The absolute values of the adjustments were 6.8 mm mean (SD 6.6 mm) with a maximum of 40 mm. All absolute values of adjustments exceeding 25 mm were recorded in one patient and those exceeding 15 mm were observed in two patients. Both patients were obese females. Adjustments exceeding 5 mm were observed in all 13 patients. Related to the use of on-line portal imaging, treatment time was increased by a median of 36.5% (mean 45.8%; SD 42.1%). The range was 7.7 to 442%. The fraction of the total treatment time to perform corrections was 22.7% median (mean: 26.0; SD: 11.8%). Statistically significant systematic in-plane errors were found in 7/13 patients. A systematic error was detected on the lateral position of the field in five patients. In one patient a systematic error of the longitudinal field position and in one patient a rotational error was detected. For adjustments in the lateral direction the present method does not allow to detect lateral shifts of less than 2 mm. For adjustments in the longitudinal direction the sensitivity could not be estimated but the available data suggest that 80% of errors < or = 5 mm were not adjusted. In obese patients, random errors may be surprisingly large. PMID- 8436531 TI - Radiographic visualization of vaginal cylinders in gynecologic high dose rate brachytherapy. AB - PURPOSE: To develop a marker system allowing an accurate determination of vaginal applicator dimensions and geometry from a radiograph. METHODS AND MATERIALS: The markers consist of two sets of gold seeds embedded into each cylinder identifying the cylinder diameter, and a thin stainless steel disk interposed between adjacent cylinders identifying their interface. An evaluation of the dosimetric properties of the markers was undertaken. An applicator was assembled using four cylinders (4 cm diameter) surrounding a stainless steel uterine tandem with a stainless steel disk 0.05 mm thick and 3.6 cm in diameter interposed between each consecutive pair of cylinders. The assembly was placed on a film and an Ir-192 high dose rate source was programmed to a single dwell position within the applicator. The markers were removed and a second film was exposed with the same dwell position and time. This procedure was repeated with various dwell positions along the applicator. A scanning densitometer was used to measure the density profiles and isodensity distributions of each film. RESULTS: The optical density profiles and isodensity distributions with and without the markers in place were identical for all source dwell positions except when the source was centered in the plane of one of the stainless steel disks, where a maximum decrease of less than 2% in the dose rate was measured. The disks had no effect on the profiles measured along axes more than 2 cm from the projection of the applicator central axis on the film. CONCLUSION: The markers provide geometrical information about the position of the applicator relative to the anatomy necessary for optimized treatment planning. Slight dose perturbations resulting from the markers do occur, but only for dwell positions that center the source in the plane of a disk, and even then only at points very close to the disk. The markers can therefore be ignored from a dosimetric point of view. PMID- 8436532 TI - Quality assurance using portal imaging: the accuracy of patient positioning in irradiation of breast cancer. AB - PURPOSE: To study the accuracy of patient positioning in irradiation of breast cancer. METHODS AND MATERIALS: Megavolt portal images were obtained using a fast electronic megavoltage radiotherapy imaging system in 17 breast cancer patients immobilized with plastic fixation masks on a flat board with arm support and in 14 patients positioned without a mask on either a flat or a wedge-shaped board. Quantitative analysis of 510 megavolt portal images and comparison to 66 digitized simulation films was performed. Differences between the positioning techniques were evaluated. RESULTS: For the position of the patient in the field, standard deviations of the difference between simulation and treatment images were 3.2 mm and 4.6 mm for irradiation with and without masks, respectively. Larger standard deviations were found for the field width and length (5-7 mm), for collimator rotation (1.5-2 degrees), and for the position of the lung shielding block for patients positioned on the flat board (10-16 mm). The changes in field size and collimator rotation appeared to be largely due to the inclination of the technologists to slightly adapt fields in order to obtain a seemingly better congruity of the field with the skin or mask markings. Comparison of the accuracy of patient positioning with and without masks yielded similar error rates; standard deviations and extremes tended to be somewhat larger in positioning without a mask. The wedge-shaped board was preferred because of the ease of patient set-up and because the use of a lung block is avoided. The transition from simulation to treatment set-up yielded larger deviations than repeated treatment set-ups. CONCLUSION: These results emphasize again the continuous need for focusing attention on the accuracy of patient positioning in order to achieve maximal precision in radiotherapy. The electronic portal imaging system is very suitable for both quick on-line treatment verification and off-line analyses. PMID- 8436533 TI - Changes in photon dose distributions due to breast prostheses. AB - PURPOSE: Subcutaneous prosthetic implants had been routinely used for cosmetic augmentation and for tissue replacement following mastectomy over the last 15 years. The implants come in many forms as the gel filler material and surrounding shell material(s) vary significantly. METHODS AND MATERIALS: This study uses a thin window parallel-plate chamber and thermoluminescent dosimeters to quantify and dosimetric changes to surrounding breast tissue due to the presence of the prosthesis. A mammographic phantom was compared to four commercial prostheses, namely two silicon gel fillers within two different shells (silicon or silicon/polyurethane), a tri-glyceride within silicon and a bio-oncotic gel within silicon/polyurethane. The latter two implants were designed with a low-Z fill for diagnostic imaging benefits. RESULTS: Ion chamber results indicate no significant alteration of depth doses away from the implant with only minor canceling (parallel opposed) interface perturbations for all implants. In addition the physical changes to the irradiated prostheses were quantified by tonometry testing and qualified by color change. Each implant exhibited color change following 50 Gy, and the bio-oncotic gel became significantly less formable following irradiation, and even less formable 6 weeks postirradiation. CONCLUSION: The data indicates that prostheses do not affect the photon beam distribution, but radiation does affect the prostheses. PMID- 8436534 TI - Evaluation of the substitution of Ir-192 seed ribbons for wires in Paris system using dose nonuniformity ratio. AB - The substitution of Ir-192 seed ribbons for wires in the Paris system of interstitial implants was re-evaluated using the dose nonuniformity ratio. The dose nonuniformity ratio, which is based on volumetric data, measures the dose nonuniformity of the implant quantitatively. The lower the dose nonuniformity ratio value, the smaller the dose nonuniformity, and the better is the dose homogeneity for the implant. Implants configured in a single-plane and double planes in the form of squares or triangles using Ir-192 wires or seed ribbons were considered. The difference between the particular reference dose rate that yielded a minimum in the dose nonuniformity ratio curve for wire implants and seed implants is about 4 cGy/hr. The difference between the minimum dose nonuniformity ratio value representing the optimal dose homogeneity of the implants is about 5%. The dose homogeneity may be considered better for implants configured using seed ribbons. PMID- 8436535 TI - Preservation of ovarian function after lateral ovarian transposition. PMID- 8436536 TI - The vanishing lymphangiogram in Hodgkin's disease: the last of the Mohicans? PMID- 8436537 TI - Factors influencing hyperthermic enhancement of drug cytotoxicity. PMID- 8436538 TI - Is effective penumbra a useful concept for MLC? PMID- 8436539 TI - Apparent heart damage after mantle irradiation, caused by subclinical hypothyroidism. PMID- 8436540 TI - Assessment of systematic error during radiotherapy. PMID- 8436541 TI - Specification of variability in positioning. PMID- 8436542 TI - Tetronothiodin, a novel cholecystokinin type-B receptor antagonist produced by Streptomyces sp. NR0489. I. Taxonomy, yield improvement and fermentation. AB - Streptomyces sp. NR0489 produces tetronothiodin, a novel brain-type cholecystokinin receptor antagonist. This species was differentiated from its related species S. gelaticus, S. griseolus and S. hydrogenans on the basis of their cultural characteristics, such as the utilization of carbohydrates and the presence or absence of various enzymatic activities. We applied the DNA-DNA hybridization method using photobiotin, which proved the genetic difference between the four species mentioned above. The yield improvement effort including single colony isolation, mutation, and protoplast regeneration together with medium optimization resulted in more than an 81-fold increase of the productivity of tetronothiodin as compared to that of the wild type strain. PMID- 8436543 TI - Tetronothiodin, a novel cholecystokinin type-B receptor antagonist produced by Streptomyces sp. NR0489. II. Isolation, characterization and biological activities. AB - A novel cholecystokinin type-B receptor antagonist named tetronothiodin has been isolated by column chromatography and preparative HPLC from the fermentation broth of Streptomyces sp. NR0489. Tetronothiodin inhibited the binding of CCK8 (C terminal octapeptide of cholecystokinin) to rat cerebral cortex membranes (CCK type-B receptors) with an IC50 of 3.6 nM, whereas it did not inhibit CCK8 binding to rat pancreatic membranes (CCK type-A receptors). It also inhibited CCK8 induced Ca2+ mobilization in GH3 cells, a rat anterior pituitary cell line, but was without effect on the basal cytosolic Ca2+ concentration. This finding indicated tetronothiodin was an antagonist of CCK type-B receptors. PMID- 8436544 TI - Animal pharmacokinetics of FK037, a novel parenteral broad-spectrum cephalosporin. AB - Single-dose pharmacokinetics of FK037 has been investigated in laboratory animals. After bolus intravenous dosing with 20 mg/kg, the elimination half-life of FK037 varied in the species; with values of 0.27, 0.30, 0.97, 1.29 and 1.76 hours in mice, rats, rabbits, dogs and monkeys, respectively. The volume of distribution ranged between 260 ml/kg in rats and 390 ml/kg in dogs. These parameters approximated those of ceftazidime and cefpirome used as reference drugs. The renal clearance of FK037 was almost equal to glomerular filtration rate (GFR) in rabbits. Probenecid did not affect the elimination half-life of FK037 and its clearance ratio to GFR. These findings suggest that FK037 is solely excreted by glomerular filtration. FK037 readily penetrated into the tissues and inflammatory exudate fluid in rats, and the tissue level was highest in the kidneys, and decreased in the following order; lungs > heart > liver > spleen. Penetration of FK037, cefpirome and ceftazidime into the cerebrospinal fluid were determined using induced staphylococcal meningitis in rabbits. The penetration percentage ranged from 14.2 to 16.0% for these drugs with no significant differences. The major route of excretion of FK037 was via the kidney, with more than 74% of the dose being excreted in the urine within 24 hours after dosing to each species. Biliary excretion was low, 0.79% in rats. Bioautograms showed only unchanged drug in the plasma, urine and bile. Serum protein binding was low (8.8 to 17.6%) in all the species studied. PMID- 8436545 TI - Microbial hydroxylation and glucuronidation of the angiotensin II (AII) receptor antagonist MK 954. AB - The microbial metabolism of MK 954 (Fig. 1), a novel nonpeptide angiotensin II receptor antagonist, was investigated using 40 microorganisms in an initial screen for cultures that will produce metabolites similar to those produced in the mammalian liver. The microbial transformation occurred under aerobic conditions in shake flasks incubated at 27 degrees C. Three metabolites of MK 954 were isolated and identified as the 1'-hydroxy M2, 3'-hydroxy M1, and glucuronic acid conjugated M3 derivatives. The structures of the metabolites were established by UV, 1H-NMR spectroscopy and FAB-MS spectrometry and are identical to metabolites produced by incubation of MK 954 with mammalian liver slices. PMID- 8436546 TI - Biphenomycin C, a precursor of biphenomycin A in mixed culture. AB - A precursor of biphenomycin A in mixed culture of Streptomyces griseorubiginosus No. 43708 with Pseudomonas maltophilia No. 1928 was isolated and characterized. The structure of the precursor, designated biphenomycin C was determined to be a peptide which is composed of biphenomycin A and arginylserine residue (Fig. 1), on the basis of chemical and spectroscopic evidence. PMID- 8436547 TI - Enzymatic dimerization of penicillin X. AB - Penicillin X methyl ester was transformed into three types of dimer by laccase from Coriolus versicolor. The dimers are considered to be formed by free-radical addition of phenoxy radicals produced by laccase. The enzyme reaction with the ester as substrate was more suitable for forming dimers than that with the sodium salt as substrate. Penicillin X pivaloyloxymethyl ester was also transformed into a dimer, which had antibacterial activity in the presence of esterase. PMID- 8436548 TI - Studies on the mode of antifungal action of pradimicin antibiotics. I. Lectin mimic binding of BMY-28864 to yeast mannan in the presence of calcium. AB - BMY-28864 (BMS-181184), a water-soluble pradimicin derivative, specifically bound on the yeast cell surface in the presence of calcium, which was considered to be the initial step that triggered chain reactions leading to the fungicidal action. Close cause-effect relationships of the cell wall binding of BMY-28864 with its antifungal activity and potassium leakage induction were observed by Candida albicans and Saccharomyces cerevisiae in the presence and absence of calcium. Using mannan and methyl alpha-D-mannopyranoside as specific sugars, the mode of binding of BMY-28864 to sugar was examined in vitro in the presence of calcium. Quantitative component analysis revealed that the precipitate of BMY-28864 with methyl alpha-D-mannopyranoside and calcium was a ternary complex possessing a molar component ratio of 2.1:4.3:1.0. These findings altogether proved that BMY 28864, although not protein, recognized specific sugars such as mannose in the same manner as lectin, and that the ternary complex formation of BMY-28864 with specific sugar and calcium was the first step for expression of the selective antifungal action of the pradimicin. PMID- 8436549 TI - Sandramycin, a novel antitumor antibiotic produced by a Nocardioides sp. II. Structure determination. AB - The structure of sandramycin, a novel antitumor antibiotic, was established by spectroscopic analysis and chiral chromatography of its acid hydrolysate. It was determined to be a cyclic decadepsipeptide with a two-fold axis of symmetry and 3 hydroxyquinaldic acid as an appended chromophore. PMID- 8436550 TI - Use of amino acid N-carboxy anhydride in the synthesis of peptide prodrug derivatives (including beta-chloroalanyl) of C4-beta-aminoalkyl carbapenems. In vitro and in vivo activities. AB - Mono- and dipeptide derivatives of C4-beta-aminoalkyl carbapenems were synthesized by the use of amino acid N-carboxy anhydride for the peptide bond formation. They were shown to act as prodrugs in vivo while imparting the much desired chemical stability. The beta-chloroalanyl derivative was suggested to act, in part, as a "dual-purpose" antibacterial. PMID- 8436551 TI - Orally active cephalosporins. II. Synthesis and structure-activity relationships of new 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-cephalospori ns with 1,2,3-triazole in C-3 side chain. AB - The synthesis, antibacterial activity and oral absorbability of 7 beta-[(Z)-2-(2 aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3 -(1H-1,2, 3-triazol-4 yl)thiomethylthio-3-cephem-4-carboxylic acid (1g) and related compounds are described. Their oral absorbability was influenced by the spacer length between C 3 of a cephem nucleus and C-4' of 1,2,3-triazole. The SCH2S structure was also found to contribute to their good oral absorption. The quantitative relationship between the bioavailability and the spacer length of cephalosporins (1a-1n) is discussed. PMID- 8436552 TI - Tetronothiodin, a novel cholecystokinin type-B receptor antagonist produced by Streptomyces sp. NR0489. III. Structural elucidation. AB - Tetronothiodin (1) is a potent and selective cholecystokinin type B (CCK-B) receptor antagonist produced by Streptomyces sp. NR0489. Its structure was elucidated to be a macrocyclic compound comprising cyclohexene, alpha acyltetronic acid and tetrahydrothiophene moieties based on various 2D NMR experiments on 1 and its dihydro derivative. The stereochemistries for the cyclohexene and tetrahydrothiophene rings were elucidated based on the analysis of NOEs obtained by NOESY experiments and NOE difference spectroscopy. The relative configuration of the cyclohexene moiety in 1 was revealed to be the same as that of the corresponding part in kijanimicin and chlorothricin, which can be structurally related to 1 in terms of their containing a cyclohexene ring with a spirotetronic acid in the molecule. PMID- 8436553 TI - Nitrosoxacins A, B and C, new 5-lipoxygenase inhibitors. PMID- 8436555 TI - Epigrisorixin, a new polyether carboxylic antibiotic. PMID- 8436554 TI - Zincphyrin, a novel coproporphyrin III with zinc from Streptomyces sp. PMID- 8436556 TI - Epocarbazolins A and B, novel 5-lipoxygenase inhibitors. Taxonomy, fermentation, isolation, structures and biological activities. AB - New 5-lipoxygenase inhibitors, designated epocarbazolins A and B, were isolated from the culture broth of Streptomyces anulatus T688-8. These compounds showed potent rat 5-lipoxygenase inhibitory activity with weak antibacterial activity. Structural studies revealed that epocarbazolins are new carbazole antibiotics having a novel substitution pattern and an epoxide in the side chain. PMID- 8436558 TI - Calbistrins, novel antifungal agents produced by Penicillium restrictum. II. Isolation and elucidation of structure. AB - The novel antifungal agents, calbistrins A, B, C and D have been isolated from a strain of Penicillium restrictum (AB 1875C-28). The four congeners were separated by bioactivity directed fractionation using countercurrent chromatography and preparative-HPLC. NMR studies revealed that the calbistrins each contain a carboxylic acid conjugated tetraene attached through an aliphatic ester linkage to a hexahydronaphthalene system. PMID- 8436557 TI - Calbistrins, novel antifungal agents produced by Penicillium restrictum. I. Production, taxonomy of the producing organism and biological activity. AB - A novel antibiotic complex, named the calbistrins, has been discovered in the culture broth of a soil fungus. The producing organism, designated AB 1875C-28, was identified as a strain of Penicillium restrictum. Calbistrin A, the most potent of the 4-membered complex, has MICs of 0.78 micrograms/ml against Candida albicans. Only poor activity is observed against non-candida yeasts, filamentous fungi and bacteria. PMID- 8436559 TI - Dactylfungins, novel antifungal antibiotics produced by Dactylaria parvispora. AB - Novel antifungal antibiotics, designated as dactylfungins A (1) and B (3), were isolated from the culture broth of Dactylaria parvispora D500. Dactylfungins A and B were found to be new substances containing an alpha-pyrone and a gamma pyrone ring, respectively, which conjoined with a polyalcohol moiety and a long side chain, based on NMR spectral analyses. The antibiotics were active against Candida pseudotropicalis and other fungi, with an MIC value at less than 10 micrograms/ml. PMID- 8436561 TI - Ferrocins, new iron-containing peptide antibiotics produced by bacteria. Taxonomy, fermentation and biological activity. AB - A Gram-negative bacterium was found to produce new iron-containing peptide antibiotics, ferrocins A, B, C and D, and the producing bacterium was characterized and identified as Pseudomonas fluorescens YK-310. These new antibiotics showed antibacterial activity against Gram-negative bacteria in vitro. Although the ferrocins showed similar antibacterial activity against both Escherichia coli and Pseudomonas aeruginosa on the standard assay media, they showed strong therapeutic effects selectively against P. aeruginosa in experimentally infected mice. PMID- 8436560 TI - Anthracycline metabolites from baumycin-producing Streptomyces sp. D788. II. New anthracycline metabolites produced by a blocked mutant strain RPM-5. AB - A daunorubicin-blocked mutant strain RPM-5 derived from a new baumycin-producing Streptomyces sp. D788 accumulated a major precursor metabolite D788-1 (10 carboxyl-13-deoxocarminomycin) and nine minor metabolites in the culture broth. Five among them were new with a substituent at C-10 or the altered side chains at C-9. Isolation, purification and identification of all anthracycline metabolites produced by strain RPM-5 are described with their antitumor activities against L1210 cells. PMID- 8436562 TI - In vitro antibacterial activity of FK037, a novel parenteral broad-spectrum cephalosporin. AB - FK037 is a new parenteral cephalosporin, which offers some advantages over the commercially available parenteral cephalosporins. It demonstrated potent broad spectrum activity against clinical isolates of Gram-positive bacteria including methicillin-resistant staphylococci, and Gram-negative bacteria including Pseudomonas aeruginosa. Against clinical isolates of aerobic Gram-positive bacteria, FK037, like cefpirome, demonstrated more potent activity than ceftazidime, cefoperazone and ceftizoxime. It is noteworthy that FK037, on the basis of the MIC90s, was the most active of all the cephalosporins tested against methicillin-resistant Staphylococcus aureus (MRSA). It was similar in activity to cefpirome against methicillin-sensitive S. aureus (MSSA). Against clinical isolates of aerobic Gram-negative bacteria, FK037, like cefpirome, was superior to cefoperazone, similar to ceftazidime and inferior to ceftizoxime in activity. Against P. aeruginosa, FK037 was superior to cefoperazone, similar or slightly superior to cefpirome and inferior to ceftazidime in activity. However, FK037 exhibited significant activity against Citrobacter and Enterobacter which were highly resistant to ceftazidime, cefoperazone and ceftizoxime. FK037 had an advantage in that its bactericidal activity against S. aureus, Escherichia coli and P. aeruginosa at sub-MICs (1/2 or 1/4 the MIC) was much stronger than those of cefpirome and ceftazidime. Moreover, it exhibited potent bactericidal activity against MSSA, MRSA and P. aeruginosa in a pharmacokinetic in vitro model simulating human plasma concentrations after intravenous dosage of 0.125, 1.0 and 1.0 g, respectively. FK037 inhibited essential penicillin-binding proteins (PBPs), 1, 2 and 3 of S. aureus with a 50% inhibitory concentration (I50) of 0.58 micrograms/ml or lower. Of essential PBPs 3, 1a and 1b of E. coli and P. aeruginosa, FK037 inhibited PBP 3 at the lowest I50 (0.03 and 0.04 micrograms/ml, respectively) and PBPs 1a and 1b with I50 values of 2.7 micrograms/ml or lower. FK037, like cefpirome, was highly stable to hydrolysis by various beta-lactamases except Ic cephalosporinase from Bacteroides fragilis, and had extremely low affinity for beta-lactamases. Therefore, FK037 was more potent than ceftazidime in activity against beta-lactamase-producing bacteria except P. aeruginosa and Serratia marcescens. The ability of FK037 to penetrate the outer membrane of E. coli was slightly higher than that of ceftazidime, but slightly lower than that of cefpirome. PMID- 8436563 TI - In vivo antibacterial activity of FK037, a novel parenteral broad-spectrum cephalosporin. AB - FK037 has potent therapeutic activity against lethal systemic infections and experimental local infections due to a wide variety of Gram-positive and Gram negative bacteria such as staphylococci, Streptococcus pneumoniae, Enterobacteriaceae and Pseudomonas aeruginosa in mice. In murine systemic infections, FK037 was the most effective of the cephalosporins and imipenem tested against highly methicillin-resistant Staphylococcus aureus (H-MRSA). It was more effective than ceftazidime against selected strains of S. aureus and Enterobacteriaceae, except Serratia marcescens and P. aeruginosa against which FK037 was as effective as ceftazidime and was as effective as cefpirome against all organisms tested, except MRSA and P. aeruginosa against which FK037 was more effective than cefpirome. These results correlated well with its in vitro activity. In murine local infections, with few exceptions, FK037 was more effective than ceftazidime and cefpirome against Klebsiella pneumonia in ED50 values and against methicillin-sensitive S. aureus (MSSA) subcutaneous abscess, pyelonephritis with Staphylococcus epidermidis, E. coli and P. aeruginosa, intrauterine infections with S. aureus and E. coli in reducing the number of viable bacteria in the abscess, kidneys and uterus. It is noteworthy that the therapeutic effects of FK037 were more potent than had been anticipated from its in vitro activity against local infections with staphylococci and P. aeruginosa when compared with ceftazidime or cefpirome. In addition, the therapeutic effects of FK037 were equipotent or superior to those of cefpirome and ceftazidime against pneumonia due to MSSA, K. pneumoniae and P. aeruginosa in reducing the number of viable bacteria in the lungs in mice using an in vivo pharmacokinetic model simulating human plasma concentrations after drip infusion of usual clinical doses (0.25 to 1.0 g for MSSA, 0.063 to 0.125 g for K. pneumoniae and 1.0 to 2.0 g for P. aeruginosa). FK037 induced an in vivo post-antibiotic effect (PAE) of 3.4 hours against a thigh infection with MSSA in neutropenic mice. These results strongly suggest that it has potential for clinical use against various infections due to bacteria which include staphylococci and P. aeruginosa. PMID- 8436565 TI - Chief complaints: the history of present symptoms. PMID- 8436564 TI - Excellent activity of FK037, a novel parenteral broad-spectrum cephalosporin, against methicillin-resistant staphylococci. AB - FK037 exhibits potent in vitro and in vivo antibacterial activity against methicillin-resistant staphylococci. In in vitro studies, FK037 was the most active of the cephalosporins and imipenem tested against the highly methicillin resistant staphylococci (MIC > 100 micrograms/ml). Only 2 of 57 strains of highly methicillin-resistant Staphylococcus aureus (H-MRSA) had a FK037 MIC value of 50 micrograms/ml. On the other hand, 55, 40 and 19 strains had MICs of 50 or > or = 100 micrograms/ml to cefpirome, flomoxef and imipenem, respectively. Against 13 strains of highly methicillin-resistant coagulase-negative staphylococci (H MRCNS), FK037 inhibited all the strains at < or = 50 micrograms/ml, but there were many strains highly resistant to the reference drugs with MICs of > or = 100 micrograms/ml. The influence of culture conditions such as low temperature, high inoculum and supplementation with 4% NaCl on the anti-MRSA activity of FK037 was less than those with cefpirome, flomoxef and imipenem. The in vitro frequency of spontaneous mutant cells highly resistant to FK037 in MRSA was lower than that to cefpirome and flomoxef. These findings were supported by lack of colonies inside the inhibition zone demarcated by FK037 in a disk sensitivity test, although many colonies proliferated inside the inhibition zone demarcated by flomoxef and imipenem. The increase in MIC of FK037 against a MRSA strain during subculture in the presence of the drug was smaller than that noted with the reference drugs. FK037 had higher affinity and faster binding for the PBP 2a of MRSA than that of the reference drugs. Moreover, the capacity to induce PBP 2a was lower for FK037 than that of cefpirome but higher than that of flomoxef. In an in vitro pharmacokinetic model simulating human plasma concentrations, FK037 showed potent bactericidal activity against H-MRSA in the plasma concentrations after intravenous infusion dosing with 1.0 g. FK037 was synergistically active against H-MRSA in combination with either imipenem of fosfomycin. The in vitro post antibiotic effect (PAE) of FK037 against H-MRSA ranged from 1.2 to 1.7 hours at one to four times the MIC. FK037 had potent therapeutic effects against lethal systemic infections and experimental local infections in mice such as pneumonia, endocarditis, subcutaneous abscess, intrauterine infection and granuloma pouch infection due to MRSA or methicillin-resistant Staphylococcus epidermidis (MRSE). FK037 was about 4, 8 and 1.5 times more effective than cefpirome, flomoxef and imipenem, respectively, against lethal systemic infections with H-MRSA.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8436566 TI - Re: Arkansas Medical Society, et al v. Department of Human Services. PMID- 8436567 TI - "Doctor, I'm in pain, but please don't hurt me." Somatization disorder: diagnosis and treatment. PMID- 8436568 TI - Continuing supervision of staff: a necessity. PMID- 8436569 TI - Case presentation of coumadin-induced skin necrosis. PMID- 8436570 TI - Porosity of porcine small-intestinal submucosa for use as a vascular graft. AB - The porosity of a vascular graft material has been suggested as a major factor affecting the rate and degree of neovascularization of newly implanted grafts, with higher porosities generally associated with better performance. The objective of this study was to determine the water porosity of a new vascular graft material, small-intestinal submucosa (SIS), and to compare the values to those reported for other common vascular graft materials. In addition, the porosity of SIS was investigated with respect to applied pressure and applied uniaxial tension. Both rectangular, flat specimens and tubular specimens of SIS were subjected to static water pressure, and water was collected as it passed through the SIS material. SIS has a typical porosity of 0.52 mL/min.cm-2 at an applied pressure of 120 mm Hg. Although porosity appeared to be unaffected by uniaxial tension, it increased in proportion to applied pressure at a rate of 4.8 x 10(-3) mL/min.cm-2/mm Hg. These low porosity values and the past success of SIS as a vascular graft material suggest that high-porosity materials are not required for implant success. PMID- 8436571 TI - Competitive adsorption of albumin against collagen at solution-air and solution polyethylene interfaces. AB - The adsorption of human serum albumin (HSA) from the binary mixtures with collagen was monitored at solution-air and solution-polyethylene interfaces by the in situ measurements. The results clearly demonstrate that on both interfaces albumin is the only adsorbing protein within a large collagen solution concentration range. At the albumin concentration equal to 0.005 mg/mL, the presence of collagen in solution results in the enhancement of albumin adsorption at solution-air interface relative to its adsorption from the single protein system. The same phenomenon is manifested at the solution-polyethylene interface, although the increase in albumin adsorption at this interface occurs at the albumin concentration equal to 0.01 mg/mL. These results are attributed to the lowering in the solution-air and solution-polyethylene interfacial tensions, and thus to the increase in the spreading characteristics of albumin in the presence of collagen molecules. The desorption experiments carried out with a buffer solution on polyethylene surfaces reveal the irreversibility of adsorbed albumin from both the single and the binary mixtures with collagen. When after 20 h of adsorption from the solutions containing albumin only, collagen was added to these solutions or when the samples after that period of time were first rinsed with a buffer and then with a collagen solution, the amounts of albumin remaining at the surfaces were in both cases reduced by one-half. PMID- 8436572 TI - Hydrolytic degradation and morphologic study of poly-p-dioxanone. AB - The in vitro hydrolytic degradation of 2-0 size PDS monofilament suture was studied for the purpose of revealing its morphologic structure and degradation mechanism. The sutures were immersed in phosphate buffer of pH 7.44 for up to 120 days at 37 degrees C. These hydrolyzed sutures were examined by the changes in tensile properties, weight, thermal properties, x-ray diffraction structure, surface morphology, and dye diffusion phenomena. It was found that hydrolysis had significant effects on the change of PDS fiber morphology and properties. Hydrolysis, however, had no significant effect on overall molecular orientation of the fiber until the very late stage. PDS suture fibers retained their skeleton throughout the earlier periods of hydrolysis concurrent with mass and tensile strength losses. PDS sutures exhibited an absorption delay of 120 days. Both heat of fusion and melting point exhibited a maximum function of hydrolysis time. Hydrolysis of PDS suture fibers proceeded through two stages: random scission of chain segments located in the amorphous regions of microfibrils and intermicrofibrillar space, followed by stepwise scission of chain segments located in the crystalline regions of microfibrils. Dye diffusion data showed that the passage along the longitudinal direction of the fiber was relatively easier than the lateral direction as evident in the diffusion coefficient, activation energy, and flexibility of chain segments. Swiss-cheese model of fiber structure appears to describe the observed dye diffusion phenomena and their dependence on hydrolysis time and dying temperature. PMID- 8436573 TI - Experimental determination of friction characteristics at the trabecular bone/porous-coated metal interface in cementless implants. AB - An apparatus was developed to measure load-displacement friction properties at the cancellous bone/porous-coated metal plate interface. Bone cubes were obtained from different proximal regions of four resurfaced cadaveric tibiae. Three different porous-surfaced metal plates (one fiber mesh and two bead) and a smooth surface metal plate were used. In the presence of a constant normal contact pressure (0.10, 0.15, or 0.25 MPa), a variable tangential load up to the maximum resistance of the interface was applied and both relative normal and tangential displacements were recorded. Repetitive and fatigue loadings were also considered. Measured results show that the interface friction curve is highly nonlinear, exhibiting large relative tangential displacements in the range of 50 400 microns before the maximum load is reached. Relative displacements in the normal direction remain below 10 microns. The maximum resistance in friction is independent of the bone excision site, type of porous-surfaced metal plate, magnitude of normal load, placement of bone cubes on metal plates or vice versa, repetition of applied load, and conservation period of bone cubes in saline solution. The smooth-surfaced metal plate has significantly smaller friction resistance than porous-coated ones. The fatigue loading of up to 4000 cycles at 1 Hz, in the presence of 0.25 MPa contact pressure, slightly decreases the interface friction coefficient. Finally, the initial secant stiffness of the interface at 75% of the maximum resistance load is found to be larger for the bone cubes from the lateral and medial regions and for the metal plate with smooth surface. PMID- 8436574 TI - Surface atomic and domain structures of biomedical carbons observed by scanning tunneling microscopy (STM). AB - STM has been used to study the surface domain and atomic structures of three biomedical carbons: glassy carbon (GC), low-temperature isotropic carbon (LTI), and ultra-low-temperature isotropic carbon (ULTI). The images show atomic lattices on both GC and LTI, but not on ULTI. The lattices contain many defects; lattices in GC are more ordered than those in LTI. The images also show patchlike carbon crystallites with sizes of 3-15 nm for GC, 2-8 nm for LTI, and 1-3 nm for ULTI. The crystallites from surface domains that may differ in surface properties due to different orientations of the crystallites. Mechanical polishing makes the LTI surface more amorphous and more homogeneous. Based on the STM observations, we evaluate several hypotheses on the blood compatibility of biomedical carbons. PMID- 8436575 TI - Post-plasma-spraying heat treatment of the HA coating/Ti-6A1-4V implant system. AB - The metal/ceramic interface that constitutes an important part of the plasma sprayed HA-coated Ti-6A1-4V system may, in fact, represent the "weak link" in the implant design. A post-plasma-spray heat treatment to enhance chemical bonding at the metal/ceramic interface and, hence, improve the mechanical properties (interface fracture toughness and tensile coating adhesion strength) of the plasma-sprayed implant system does show promise. In preliminary heat treatment studies, however, any improvements realized were lost due to the chemical instability of the coating in a moisture-laden environment, with a concomitant loss in bonding properties. This deterioration in properties appears to be related to environmentally assisted crack growth as influenced by processing conditions. Still, an ability to improve HA/Ti-6A1-4V bonding through enhanced diffusion bonding was demonstrated, warranting further heat treatment studies involving atmosphere control during processing. PMID- 8436576 TI - Cell adhesion onto block copolymer Langmuir-Blodgett films. AB - The attachment of cells onto the surfaces of various block copolymers fabricated either as well-defined, ordered Langmuir-Blodgett (LB) films, or solvent cast microphase-separated structures was studied. In general, more platelets adhered onto the multilayered LB surface than onto microphase-separated cast surfaces. Scanning electron micrographs of adhered platelets showed extensive morphological changes associated with the LB surface as compared to cast film surfaces. The morphology of adhered hepatocytes was similar for both LB films and cast surfaces. It may be assumed that the surface of a block copolymer LB film does not orient into microdomains, as in the solvent cast surfaces, and only one polymer domain interacts at the interface. PMID- 8436577 TI - Determination of the role of cuticular carbohydrates in the hemocompatibility of Dirofilaria immitis (Nematoda). AB - We have partially characterized surface glycoproteins of the canine heartworm, Dirofilaria immitis. Histochemical studies indicated the presence of neutral and acidic mucopolysaccharides at the blood-cuticle interface. Fluorescein isothiocyanate-conjugated lectin binding patterns suggested the presence of alpha D-glucosyl and/or alpha-D-mannosyl, beta-galactosyl, N-acetylneuraminyl and N acetylated-D-hexosaminyl (sialic and glucuronic acids, respectively) terminal residues among the constituent sugars of the glycocalyx. An additional goal of this study was to assess the significance of each carbohydrate in parasite hemocompatibility by using scanning electron microscopy, internal reflection infrared spectroscopy, and comprehensive contact angle measurements. Each carbohydrate identified in the glycocalyx was selectively cleaved with the appropriate exoglycosidase. Heart-worms bearing native and enzyme-altered surfaces were exposed to platelet-rich canine plasma. Activation and aggregation of platelets were significantly increased on enzyme-treated surfaces as compared with native surfaces. Enzyme-induced cleavage of carbohydrate residues was associated with an increase in critical surface tension or a loss in cuticular structural integrity or both. Hemocompatibility of the heartworm cuticle depends on the retention of a stable saccharide-rich layer that minimizes interaction with plasma proteins and platelets; thus, carbohydrate residues on the glycocalyx may contribute to parasite hemocompatibility. The presence of similar low critical-surface-tension coatings with high mechanical integrity may impart thromboresistance to other polyphenolic or chitinous substances. PMID- 8436578 TI - A critical evaluation of the purification of biominerals by hypochlorite treatment. AB - The quantitative deproteination of calcific deposits from surgically explanted heart valve bioprostheses was carried out by both hypochlorite and hydrazine extraction to establish which is the better procedure for preparing purified mineral suitable for detailed chemical and structural characterization. Hypochlorite treatment resulted in a material with a higher Ca/PO4 ratio than that of the untreated deposits. The hydrazine treatment did not produce such an effect. A systematic comparison of x-ray diffraction patterns of calcific deposits showed an increase in crystallinity of hypochlorite-treated versus native material, while the crystallinity of hydrazine-treated materials did not change. One other result of the hypochlorite treatment was a pronounced disaggregation of well-ground calcific deposits into a particle populations ranging from 50-300 nm in size, as shown by scanning electron microscopy. Results comparable to the above findings were also obtained when the two treatments were applied to other bioapatites. On the other hand, mineral solubilities were comparable, regardless of which deproteination treatment was used. The principal conclusion from this study is that hydrazine deproteination is preferable to hypochlorite extraction in isolating pathologic mineral deposits from bioprosthetic materials for further study. PMID- 8436579 TI - Uptake of metal cations by fibroblasts in vitro. AB - Atomic absorption spectroscopy was used to assess uptake of Ag+1, Au+4, Cd+2, Cu+2, In+3, Ni+2, Pd+2, and Zn+2 by in vitro cultures of Balb/c 3T3 fibroblasts as a function of concentration of the cations in cell-culture medium. Reversibility of this uptake was also measured. Metal cations exhibited a 400 fold difference in their tendency to accumulate in the cells; In+3 tended to accumulate the most, whereas Pd+2 accumulated the least. Uptake of the cations in the cells increased linearly with the concentration of the cation in the medium for all cations up to their 50% toxicity concentrations. Reversal of this uptake was slower than that of the initial uptake for three cations studied in more detail (Cd+2, In+3, and Ni+2). The duration of the initial exposure affected the proportion of the metal cations that were retained by the cells 5 h after the cations were removed from the medium. The proportion of retained Cd+2 did not change when the initial exposure was increased from 2 h to 6 h, whereas the proportion of retained In+3 decreased and Ni+2 increased over the same period. The tendency of the cells to accumulate these cations correlated with their cytotoxic potency (measured previously). PMID- 8436580 TI - Application of the quinolone antibiotic ciprofloxacin to Dacron utilizing textile dyeing technology. AB - Prosthetic arterial graft infection continues to be a significant and often devastating complication of vascular surgery. The organisms Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis) are the primary pathogens causing acute and late graft infections, respectively. The objective of this study was to develop an infection-resistant prosthetic arterial graft by applying the bacteriocidal quinolone antibiotic ciprofloxacin to polyethylene terepthalate (Dacron) via thermofixation (pad/heat), a new application method founded on established textile procedures. We hypothesize that the limited fibrophilic characteristics of ciprofloxacin will permit binding to Dacron and at the same time allow persistent controlled release over an extended period of time. Using pad/heat technology, 33 micrograms (+/- 2.97 micrograms, n = 12) of ciprofloxacin was successfully bound to a 1-cm2 piece of woven Dacron. A full complement of microbiologic assays demonstrated superior, sustained antistaphylococcal activity of the pad/heat Dacron when compared to Dacron dipped into an equivalent concentration of ciprofloxacin. The sustained antimicrobial efficacy of ciprofloxacin pad/heat-treated Dacron opens new avenues in the development of infection-resistant biomaterials based on an understanding of textile chemistry. PMID- 8436581 TI - The functional equivalence of demineralized bone and tooth matrices in ectopic bone induction. AB - The objective of this study was to determine whether demineralized rat incisor matrices were a more potent inducer of ectopic endochondral bone formation than demineralized diaphyseal bone matrices derived from the same donors. Twenty-five milligram disks of demineralized bone or tooth matrix obtained from adolescent Long-Evans rats were implanted in a standardized ectopic site. Biochemical and histometric measurements of bone formation revealed that the two matrices were functionally equivalent inducers of endochondral bone formation. The induced pellicle of bone reached a maturation point 18 days after implantation. Dentin matrix implants generated a significantly greater amount of mineralized tissue than did bone matrix implants. This difference could be explained on the basis of remineralization of the dentin particles to a greater degree than the bone matrix particles. Initial observations suggesting a more robust osteoinductive activity in demineralized incisor matrix can be attributed to the decreasing activity of bone matrix from older donors when compared to younger donors. The extent of osteoinduction by the two substrata was equivalent when the matrices were matched for age. PMID- 8436582 TI - Ingrowth of bone into pores in titanium chambers implanted in rabbits: effect of pore cross-sectional shape in the presence of dynamic shear. AB - The micromotion chamber consists of a titanium outer cylinder and a central core, which are pierced by a transverse 1-mm canal for tissue ingrowth. Six weeks after implantation in the proximal tibia in mature rabbits, the outer cylinder is osseointegrated; the central core can then be moved in relation to the fixed outer cylinder. Thus, the tissue growing through the pore, from the cylinder into the core, can be subjected to motion of a predetermined amplitude and frequency. In this study we investigate the influence of pore cross-sectional shape on tissue ingrowth in the canal. In six animals, the outer cylinder was pierced by a square 1-mm hole that was congruent with the square hole in the core; in five animals, the hole in the cylinder was round. The cross-sectional area of the square hole in the cylinder was about 21% greater than in a round hole. In all cases, the channel in the inner core was 1 x 1 x 5-mm quadrate. All chambers underwent 20 cycles/day of micromotion for a 3-week period. The amplitude of the micromotion was 0.5 mm. Chambers containing cylinders with a round hole demonstrated less bone ingrowth as compared to cylinders with a square hole. This observation may be due to several factors including the greater cross-sectional area of the square versus the round hole in the cylinder and the enhanced congruity provided by the square outer and inner holes, versus a round outer and square inner hole. PMID- 8436583 TI - Protein adsorption onto poly(ether urethane ureas) containing Methacrol 2138F: a surface-active amphiphilic additive. AB - Surface characterization and protein adsorption studies were carried out on a series of additive dispersed and additive coated poly(ether urethane ureas), PEUUs, to characterize early events in the blood compatibility of these materials. A hypothesis that is based on surface hydrophilicity, surface flexibility, and adsorption media has been developed to understand the modulated adsorption of plasma proteins by PEUU additives. Electron spectroscopy for chemical analysis (ESCA) and contact angle analysis were performed on two PEUU formulation as well as on PEUU formulations modified with Methacrol 2138F (co[diisopropylaminoethyl methacrylate (DIPAM)/decyl methacrylate (DM)][3/1]) or acrylate or methacrylate polymer or copolymer analogs of Methacrol 2138F. Methacrol 2138F is a commercially used amphiphilic copolymethacrylate. ESCA showed that the PEUUs loaded with Methacrol 2138F or with its hydrophilic component, homopoly (DIPAM) (h-(DIPAM)), had a higher percentage of nitrogen at their surfaces than did the base PEUUs. Contact angle analysis also showed that the air side of PEUU formulations loaded with Methacrol 2138F were more hydrophobic than was the air side of base PEUUs when films were cast from dimethylacetamide. However, during contact angle testing, the air side of PEUU films loaded with Methacrol 2138F rapidly became more hydrophilic than did the air side of the base PEUU films. A radioimmunoassay and whole or diluted human plasma were also used to characterize the presence of the proteins fibrinogen, immunoglobulin G, factor VIII/von Willebrand factor, Hageman factor (factor XII), and albumin, on the surface of the same PEUUs as analyzed by ESCA and contact angle. The protein adsorption assay showed that PEUU films loaded or coated with Methacrol 2138F, with a copolyacrylate analog of Methacrol 2138F (co(diisopropylaminoethyl acrylate [DIPAA]/decyl acrylate [DA]) [3/1]), or with the hydrophilic polyacrylate or polymethacrylate component analogs of Methacrol 2138F (h-DIPAM or h-DIPAA) adsorbed significantly lower amounts of the proteins than did either the base PEUU formulations or the homopoly(decyl methacrylate) (h DM) or homopoly(decyl acrylate) (h-DA) coated or loaded PEUUs. PMID- 8436584 TI - 111Indium labeling of microorganisms to facilitate the investigation of bacterial adhesion. AB - The ability of bacteria to adhere to polymeric interfaces has attracted considerable attention in recent years. Metabolic labeling of microorganisms with 35S-methionine or other beta-emitters is commonly utilized for quantification of bacterial adhesion to biopolymers. Since the use of these isotopes is cumbersome, the possibility of labeling the microorganisms with 111Indium, a strong gamma emitter, was explored. This report demonstrates that bacteria can be easily labeled with 111Indium. Staphylococcus aureus, Staphylococcus epidermiids, and Pseudomonas aeruginosa were labeled with either 111Indium-oxine or 35S methionine; and labeling efficiency, retention of incorporated labels, and growth kinetics of labeled bacteria were compared under identical experimental conditions. Bacteria labeled with 111In-oxine incorporated approximately 90% of radioactivity within 10 min, whereas 35S-methionine incorporation required many hours of incubation. Both the incorporated isotopes were gradually released by rapidly growing bacteria into the suspension medium. Of the total incorporated labels, approximately 20% 111In and 15% 35S were released in the surrounding medium every 24 h. No release of incorporated labels occurred when cells were fixed with 2.5% buffered glutaraldehyde. Growth kinetics and scanning or transmission electron microscopic analysis showed no detectable differences among control (nonlabeled), 111In-, or 35S-labeled bacteria. Labeling of bacteria with 111In-oxine does not interfere with bacterial adherence. These observations suggest that 111In incorporation provides a simple and rapid method of labeling of microorganisms. Compared to currently available techniques, the use of 111In labeled bacteria will facilitate the quantitation of adherent bacteria to interfaces. PMID- 8436585 TI - Inorganic bone and demineralized bone matrix impregnated bone cement: a preliminary in vivo study. PMID- 8436586 TI - The constitutive and stress inducible forms of hsp 70 exhibit functional similarities and interact with one another in an ATP-dependent fashion. AB - Mammalian cells constitutively express a cytosolic and nuclear form of heat shock protein (hsp) 70, referred to here as hsp 73. In response to heat shock or other metabolic insults, increased expression of another cytosolic and nuclear form of hsp 70, hsp 72, is observed. The constitutively expressed hsp 73, and stress inducible hsp 72, are highly related proteins. Still unclear, however, is exactly why most eukaryotic cells, in contrast to prokaryotic cells, express a novel form of hsp 70 (i.e., hsp 72) after experiencing stress. To address this question, we prepared antibodies specific to either hsp 72 or hsp 73 and have compared a number of biological properties of the two proteins, both in vivo and in vitro. Using metabolic pulse-chase labeling and immunoprecipitation analysis, both the hsp 72 and hsp 73 specific antibodies were found to coprecipitate a significant number of newly synthesized proteins. Such interactions appeared transient and sensitive to ATP. Consequently, we suspect that both hsp 72 and hsp 73 function as molecular chaperones, interacting transiently with nascent polypeptides. During the course of these studies, we routinely observed that antibodies specific to hsp 73 resulted in the coprecipitation of hsp 72. Similarly, antibodies specific to hsp 72 were capable of coprecipitating hsp 73. Using a number of different approaches, we show that the constitutively expressed, pre existing hsp 73 rapidly forms a stable complex with the newly synthesized stress inducible hsp 72. As is demonstrated by double-label indirect immunofluorescence, both proteins exhibit a coincident locale within the cell. Moreover, injection of antibodies specific to hsp 73 into living cells effectively blocks the ability of both hsp 73 and hsp 72 to redistribute from the cytoplasm into the nucleus and nucleolus after heat shock. These results are discussed as they relate to the possible structure and function of the constitutive (hsp 73) and highly stress inducible (hsp 72) forms of hsp 70, both within the normal cell as well as in the cell experiencing stress. PMID- 8436587 TI - Localization of TGN38 to the trans-Golgi network: involvement of a cytoplasmic tyrosine-containing sequence. AB - Protein localization to the TGN was investigated by examining the subcellular distribution of chimeric proteins in which the cytoplasmic and/or transmembrane domains of the TGN protein, TGN38, were substituted for the analogous domains of the plasma membrane protein, Tac. Using immunofluorescence and immunoelectron microscopy, the COOH-terminal cytoplasmic domain of TGN38 was found to be sufficient for localization of the chimeric proteins to the TGN. Deletion analysis identified an 11-amino acid segment containing the critical sequence, YQRL, as being sufficient for TGN localization. TGN localization was abrogated by mutation of the tyrosine or leucine residues in this sequence to alanine, or of the arginine residue to aspartate. In addition to specifying TGN localization, the 11-amino acid segment was active as an internalization signal, although the property of internalization alone was insufficient to confer TGN localization. Overexpression of chimeric proteins containing TGN localization determinants resulted in their detection at the plasma membrane and in intracellular vesicles, and abolished detection of endogenous TGN38. These results suggest that discrete cytoplasmic determinants can mediate protein localization to the TGN, and reveal a novel role for tyrosine-based motifs in this process. PMID- 8436589 TI - A 27,000-D core of the Dictyostelium 34,000-D protein retains Ca(2+)-regulated actin cross-linking but lacks bundling activity. AB - Actin cross-linking proteins are important for formation of isotropic F-actin networks and anisotropic bundles of filaments in the cytoplasm of eucaryotic cells. A 34,000-D protein from the cellular slime mold Dictyostelium discoideum mediates formation of actin bundles in vitro, and is specifically incorporated into filopodia. The actin cross-linking activity of this protein is inhibited by the presence of micromolar calcium. A 27,000-D fragment obtained by digestion with alpha-chymotrypsin lacks the amino-terminal six amino acids and the carboxyl terminal 7,000 D of the intact polypeptide. The 27,000-D fragment retains F-actin binding activity assessed by cosedimentation assays and by 125I-[F-actin] blot overlay technique, F-actin cross-linking activity as assessed by viscometry, and calcium binding activity. Ultrastructural analyses indicate that the 27,000-D fragment is deficient in the bundling activity characteristic of the intact 34,000-D protein. Actin filaments are aggregated into microdomains but not bundle in the presence of the 27,000-D fragment. A polarized light scattering assay was used to demonstrate that the 34,000-D protein increases the orientational correlation among F-actin filaments. The 27,000-D fragment does not increase the orientation of the actin filaments as assessed by this technique. A terminal segment(s) of the 34,000-D protein, lacking in the 27,000-D fragment, contributes significantly to the ability to cross-link actin filaments into bundles. PMID- 8436588 TI - Complementary distributions of vinculin and dystrophin define two distinct sarcolemma domains in smooth muscle. AB - The sarcolemma of the smooth muscle cell displays two alternating structural domains in the electron microscope: densely-staining plaques that correspond to the adherens junctions and intervening uncoated regions which are rich in membrane invaginations, or caveolae. The adherens junctions serve as membrane anchorage sites for the actin cytoskeleton and are typically marked by antibodies to vinculin. We show here by immunofluorescence and immunoelectron microscopy that dystrophin is specifically localized in the caveolae-rich domains of the smooth muscle sarcolemma, together with the caveolae-associated molecule caveolin. Additional labeling experiments revealed that beta 1 integrin and fibronectin are confined to the adherens junctions, as indicated by their codistribution with vinculin and tensin. Laminin, on the other hand, is distributed around the entire cell perimeter. The sarcolemma of the smooth muscle cell is thus divided into two distinct domains, featuring different and mutually exclusive components. This simple bipartite domain organization contrasts with the more complex organization of the skeletal muscle sarcolemma: smooth muscle thus offers itself as a useful system for localizing, among other components, potential interacting partners of dystrophin. PMID- 8436590 TI - Regulation of cytoplasmic division of Xenopus embryo by rho p21 and its inhibitory GDP/GTP exchange protein (rho GDI). AB - Evidence is accumulating that the rho family, a member of the ras p21-related small GTP-binding protein superfamily, regulates cell morphology, cell motility, and smooth muscle contraction through the actomyosin system. The actomyosin system is also known to be essential for cytoplasmic division of cells (cytokinesis). In this study, we examined the action of rho p21, its inhibitory GDP/GTP exchange protein, named rho GDI, its stimulatory GDP/GTP exchange protein, named smg GDS, and botulinum ADP-ribosyltransferase C3, known to selectively ADP-ribosylate rho p21 and to impair its function, in the cytoplasmic division using Xenopus embryos. The sperm-induced cytoplasmic division of Xenopus embryos was not affected by microinjection into the embryos of either smg GDS or the guanosine-5'-(3-O-thio)triphosphate (GTP gamma S)-bound form of rhoA p21, one member of the rho family, but completely inhibited by microinjection of rho GDI or C3. Under these conditions, nuclear division occurred normally but the furrow formation, which was induced by the contractile ring consisting of actomyosin just beneath the plasma membrane, was impaired. Comicroinjection of rho GDI with the GTP gamma S-bound form of rhoA p21 prevented the rho GDI action. Moreover, the sperm-induced cytoplasmic division of Xenopus embryos was inhibited by microinjection into the embryos of the rhoA p21 pre-ADP-ribosylated by C3 which might serve as a dominant negative inhibitor of endogenous rho p21. These results indicate that rho p21 together with its regulatory proteins regulates the cytoplasmic division through the actomyosin system. PMID- 8436591 TI - Inhibition of mos-induced oocyte maturation by protein kinase A. AB - The relationship between the mos protooncogene protein and cAMP-dependent protein kinase (PKA) during the maturation of Xenopus oocytes was investigated. Microinjection of the PKA catalytic subunit (PKAc) into Xenopus oocytes inhibited oocyte maturation induced by the mos product but did not markedly affect the autophosphorylation activity of injected mos protein. By contrast, PKAc did not inhibit maturation promoting factor (MPF) activation or germinal vesicle breakdown (GVBD) that was initiated by injecting crude MPF preparations. In addition, inhibiting endogenous PKA activity by microinjecting the PKA regulatory subunit (PKAr) induced oocyte maturation that was dependent upon the presence of the endogenous mos product. Moreover, PKAr potentiated mos protein-induced MPF activation in the absence of progesterone and protein synthesis. These data are consistent with the hypothesis that progesterone-induced release from G2/M is regulated via PKAc and that PKAc negatively regulates a downstream target that is positively regulated by mos. PMID- 8436592 TI - Spatial and temporal dissection of immediate and early events following cadherin mediated epithelial cell adhesion. AB - Cell-cell adhesion is at the top of a molecular cascade of protein interactions that leads to the remodeling of epithelial cell structure and function. The earliest events that initiate this cascade are poorly understood. Using high resolution differential interference contrast microscopy and retrospective immunohistochemistry, we observed that cell-cell contact in MDCK epithelial cells consists of distinct stages that correlate with specific changes in the interaction of E-cadherin with the cytoskeleton. We show that formation of a stable contact is preceded by numerous, transient contacts. During this time and immediately following formation of a stable contact, there are no detectable changes in the distribution, relative amount, or Triton X-100 insolubility of E cadherin at the contact. After a lag period of approximately 10 min, there is a rapid acquisition of Triton X-100 insolubility of E-cadherin localized to the stable contact. Significantly, the total amount of E-cadherin at the contact remains unchanged during this time. The increase in the Triton X-100 insoluble pool of E-cadherin does not correlate with changes in the distribution of actin or fodrin, suggesting that the acquisition of the Triton X-100 insolubility is due to changes in E-cadherin itself, or closely associated proteins such as the catenins. The 10 minute lag period, and subsequent prompt and localized nature of E-cadherin reorganization indicate a form of signaling is occurring. PMID- 8436595 TI - Heat shock alters centrosome organization leading to mitotic dysfunction and cell death. AB - To identify the cellular target(s) responsible for thermal killing in the G1 phase of the cell cycle, synchronous cultures of Chinese hamster ovary cells (CHO) were heat shocked and studied for one cell cycle by time-lapse videomicroscopy and immunocytochemistry. At the first mitosis post-heating, the fraction of cells giving rise to multinucleated progeny approximately equaled the nonclonogenic fraction. In addition, the cells yielding multinucleated progeny were delayed in prophase-metaphase relative to the cells yielding two uninucleated progeny (clonogenic cells). To study the basis for the delay in prophase-metaphase and subsequent formation of multinucleated cells, cells in mitosis were examined by immunofluorescence for spindle abnormalities. Multipolar mitotic spindles and chromosome misalignment were induced by heat. All multiple spindle poles induced by heat stained for pericentriolar material (PCM), the microtubule nucleating material of centrosomes. Heated cells in mitosis also contained additional foci of PCM which were not associated with the spindle. Cells made thermotolerant by a nonlethal heat shock were resistant to both thermal killing and the induction of multiple foci of PCM. Quantitative analysis revealed a good correlation between the fraction of cells with multipolar spindles, the fraction with more than two foci of PCM, and the nonclonogenic fraction. These data indicate that heat-induced alterations to the PCM of centrosomes resulted in multipolar mitotic spindles, delay in prophase-metaphase, and formation of multinucleated cells which were nonclonogenic. These results identify the centrosome as a G1 target for cell killing. PMID- 8436594 TI - Interleukin-6 undergoes transition from paracrine growth inhibitor to autocrine stimulator during human melanoma progression. AB - The ability to penetrate the dermal basement membrane and subsequently proliferate in the underlying mesenchyme is one of the key steps in malignant progression of human melanomas. We previously undertook studies aimed at assessing how normal dermal fibroblasts (one of the main cellular components of mesenchyme) may affect the growth of human melanoma cells and facilitate the overgrowth of malignant subpopulations (Cornil, I., D. Theodorescu, S. Man, M. Herlyn, J. Jambrosic, and R. S. Kerbel. 1991. Proc. Natl. Acad. Sci. USA. 88:6028 6032). We found that melanoma cell lines from early-stage (metastatically incompetent) lesions were growth inhibited whereas those from advanced-stage (metastatically competent) lesions were stimulated under the same conditions by co-culture with fibroblasts; conditioned medium from such cells gave the same result. Subsequent studies using biochemical purification and neutralizing antibodies revealed the inhibitory activity to be identical to interleukin-6 (IL 6). We now report that addition of purified recombinant human IL-6 resulted in a growth inhibition in vitro by G1/G0 arrest of early, but not advanced stage melanoma cells. Despite this alteration in response there was no significant difference in melanoma cell lines of varying malignancy in respect to their expression of genes encoding the IL-6 receptor, or gp130, the IL-6 signal transducer. Scatchard analysis also revealed similar [125I]IL-6 binding activities in both IL-6 sensitive and resistant groups. However, studies of IL-6 production indicated that five out eight IL-6 melanoma cell lines known to be resistant to exogenous IL-6-mediated growth inhibition constitutively expressed mRNA for IL-6; they also secreted bioactive IL-6 into culture medium. To assess the possible role of this endogenous IL-6 in melanoma cell growth, antisense oligonucleotides to the IL-6 gene were added to cultures of melanoma cells. This resulted in a significant growth inhibition only in cell lines that produced endogenous IL-6. In contrast, neutralizing antibodies to IL-6 were ineffective in causing such growth inhibition. This indicates that endogenous IL-6 may behave as a growth stimulator by an intracellular ("private") autocrine mechanism. Thus, a single cytokine, IL-6, can switch from behaving as a paracrine growth inhibitor to an autocrine growth stimulator within the same cell lineage during malignant tumor progression. Such a switch may contribute to the growth advantage of metastatically competent melanoma cells at the primary or distant organ sites and thereby facilitate progression of disease. PMID- 8436593 TI - Posttranscriptional regulation of GAP-43 gene expression in PC12 cells through protein kinase C-dependent stabilization of the mRNA. AB - We have previously shown that nerve growth factor (NGF) selectively stabilizes the GAP-43 mRNA in PC12 cells. To study the cellular mechanisms for this post transcriptional control and to determine the contribution of mRNA stability to GAP-43 gene expression, we examined the effects of several agents that affect PC12 cell differentiation on the level of induction and rate of degradation of the GAP-43 mRNA. The NGF-mediated increase in GAP-43 mRNA levels and neurite outgrowth was mimicked by the phorbol ester TPA, but not by dibutyryl cAMP or the calcium ionophore A12783. Downregulation of protein kinase C (PKC) by high doses of phorbol esters or selective PKC inhibitors prevented the induction of this mRNA by NGF, suggesting that NGF and TPA act through a common PKC-dependent pathway. In mRNA decay studies, phorbol esters caused a selective 6-fold increase in the half-life of the GAP-43 mRNA, which accounts for most of the induction of this mRNA by TPA. The phorbol ester-induced stabilization of GAP-43 mRNA was blocked by the protein kinase inhibitor polymyxin B and was partially inhibited by dexamethasone, an agent that blocks GAP-43 expression and neuronal differentiation in PC12 cells. In contrast, the rates of degradation and the levels of the GAP-43 mRNA in control and TPA-treated cells were not affected by cycloheximide treatment. Thus, changes in GAP-43 mRNA turnover do not appear to require continuous protein synthesis. In conclusion, these data suggest that PKC activity regulates the levels of the GAP-43 mRNA in PC12 cells through a novel, translation-independent mRNA stabilization mechanism. PMID- 8436596 TI - Extracellular matrix produced by cultured corneal and aortic endothelial cells contains active tissue-type and urokinase-type plasminogen activators. AB - Incubation of plasminogen with the subendothelial extracellular matrix (ECM) synthesized by cultured bovine corneal and aortic endothelial cells resulted in generation of fibrinolytic activity, indicated by proteolysis of 125I-fibrin in a time- and dose-dependent manner. Both tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA) were identified in the ECM by fibrin zymography, immunoblotting, and inhibition of plasminogen activation by anti-u-PA and anti-t-PA antibodies. Most of the ECM-resident plasminogen activator (PA) activity did not originate from intracellular PA release occurring when the endothelial cells were lyzed and the ECM exposed, since a comparable amount of PA was associated with the ECM when the cells were lyzed with Triton X 100 or removed intact by treatment with 2 M urea. Active u-PA and t-PA were released from ECM by treatment with heparanase (endo-beta-D-glucuronidase), indicating that some of the ECM-resident PA activity is sequestered by heparan sulfate side chains. These results indicate that both u-PA and t-PA produced by endothelial cells are firmly sequestered in an active form by the subendothelial ECM. It is suggested that ECM-resident plasminogen activators participate in sequential matrix degradation during cell invasion and tumor metastasis. PA activity may also function in release of ECM-bound growth factors (i.e., basic fibroblast growth factor) and activation of proenzymes (i.e., prothrombin), resulting in modulation of the ECM growth-promoting and thrombogenic properties. PMID- 8436597 TI - Regulation of neutrophil interleukin 8 gene expression and protein secretion by LPS, TNF-alpha, and IL-1 beta. AB - Neutrophils are possibly involved in the pathogenesis of various lung diseases through the release of numerous mediators. In the present study, we studied the regulation of IL-8 gene induction and protein secretion in human blood neutrophils. Northern blot analysis revealed that LPS increased IL-8 mRNA levels in neutrophils, with a maximal fivefold increase by 2 h. IL-8 mRNa levels returned to baseline values within 12 h. In contrast, LPS-stimulated monocytes demonstrated a sustained increase of IL-8 mRNA levels for more than 24 h. TNF alpha, IL-1 beta, and phorbol myristate acetate also increased IL-8 mRNA levels in neutrophils. Immunohistochemical analysis confirmed that IL-8 was localized within stimulated neutrophils. IL-8 secretion by neutrophils and monocytes was quantified using a specific ELISA for IL-8. Resting neutrophils secreted minimal IL-8 activity. However when cells were stimulated with LPS, TNF-alpha, or IL-1B, neutrophils secreted IL-8. IL-8 secretion was most marked during the first 2 h after stimulation and decreased thereafter. In contrast, monocytes maintained a high rate of IL-8 secretion over 12 h. Although a single monocyte secreted 70 fold more IL-8 than did a single neutrophil after 4 h of incubation, the high abundance of neutrophils in peripheral blood made the neutrophil-secreted IL-8 more significant. During the first 2 h, neutrophils secreted approximately 40% of the IL-8 released by monocytes in the same volume of blood. This ratio decreased to 9% after 12 h. Neutrophil-secreted IL-8 may play an autocrine or paracrine role during the initial stage of inflammation. PMID- 8436599 TI - Low oxygen stimulates proliferation of fibroblasts seeded as single cells. AB - In standard tissue culture conditions (20% oxygen), single human dermal fibroblasts (one cell per well) do not proliferate. We now report that low oxygen tension is a potent stimulus for the proliferation and expansion of human adult and neonatal dermal fibroblasts seeded as single cells. This preferential single cell proliferation in low oxygen is shown to be also a feature of human lung and dermal rodent fibroblasts, but not of human fibrosarcoma and immortalized 3T3 cells, which proliferate without difficulty in standard oxygen conditions. It is suggested that single-cell proliferation and its dramatic stimulation in low oxygen may represent a fundamental biologic process with an opportunity to better understand mammalian cell growth regulation. PMID- 8436598 TI - Platelet-activating factor secreted by DDAVP-treated monocytes mediates von Willebrand factor release from endothelial cells. AB - We have previously shown that although DDAVP (1-deamino-8-D-arginine vasopressin), a synthetic analogue of the natural hormone arginine vasopressin, does not directly promote release of vWf from human umbilical vein endothelial cells (ECs), enhanced release does occur when ECs were exposed to either monocytes or to supernatants recovered from DDAVP-treated monocytes. In the present study, we have found that exposure of monocytes to DDAVP did not increase secretion of interleukins (IL)-1 beta, IL-6, IL-8, tumor necrosis factor (TNF alpha), growth factors G-CSF (granulocyte-), GM-CSF (granulocyte, monocyte-colony stimulating factor), prostaglandins (PG) E2, PGF2 alpha, or PGI2 or purine nucleotides such as ATP and ADP. However, increased levels of platelet-activating factor (PAF) were secreted by DDAVP-treated monocytes in a time- and dose dependent manner that positively correlated with the enhancement in vWf release from ECs. Moreover, this effect could also be elicited when lipid extracts of these supernatants or purified PAF were added directly to ECs. This response could be inhibited with (+/-)-trans-2,5-Bis(3,4,5-trimethoxyphenyl)-1,3 dioxolane, a specific PAF receptor antagonist, when the ECs were exposed to supernatants from DDAVP-treated monocytes or to pure PAF. The present data indicate that enhanced secretion of PAF from monocytes is one mechanism whereby DDAVP can provoke release of vWf from ECs. PMID- 8436600 TI - Stimulation of bone resorption and osteoclast clear zone formation by low pH: a time-course study. AB - The significance of low pH-induced stimulation of osteoclastic bone resorption has recently been questioned following the finding that embryonic chick osteoclasts were only weakly stimulated by extremely low pH (6.5) and that the effect was transient, apparently due to cytotoxicity. Although low pH in the range 6.8-7.2 is known to stimulate rat osteoclasts over 24 h, the long-term effects of low pH on mammalian osteoclasts are not known. We have therefore conducted time-course studies over 72 h on the effect of pH in the range 6.3-7.3 on bone resorption and cytotoxicity in both rat and chick osteoclasts. In neonatal rat osteoclasts, lowering extracellular pH produced a powerful and significant stimulation of resorption over 24 h. Detailed analysis of the resorption focus revealed that this was due mainly to a higher proportion of active osteoclasts at lower pH. In addition, osteoclasts excavated slightly larger pits at low pH. Stimulation was no longer significant at 72 h, however, due to a pH-dependent slowing of resorption at acid pH associated 1) with cytotoxicity primarily of nonosteoclastic cells and 2) with an acceleration of bone resorption after 24 h at more alkaline pH. Resorption stimulated by low pH was associated with the formation of actin-rich "clear zones" within the osteoclast. Chick osteoclasts were less sensitive to low pH than rat osteoclasts but nonetheless showed a consistently higher level of resorption at low pH over 24-72 h. These results suggest that protons play an important regulatory role in neonatal rat osteoclasts, and stimulate the formation of clear zones. The lower sensitivity of the chick osteoclast to acid pH may be due to a species difference or the chick osteoclast's higher basal level of resorption. PMID- 8436601 TI - Microscale autoradiographic method for the qualitative and quantitative analysis of apoptotic DNA fragmentation. AB - A method combining the advantages of electrophoretic DNA fractionation and autoradiography is described for the qualitative and quantitative analysis of internucleosomal DNA fragmentation that occurs during apoptosis, or "programmed cell death." This procedure utilizes terminal transferase enzyme to uniformly add one molecule of [alpha 32P]-dideoxynucleotide to the 3'-end of DNA fragments. Following gel electrophoresis and autoradiographic analysis, the total amount of radiolabel incorporated into the low molecular weight DNA fraction can be quantitated and used to estimate the degree of apoptotic DNA fragmentation in any given sample. This method requires as little as 15 ng of total cellular DNA and increases the sensitivity of apoptotic DNA detection by at least 100-fold over the widely used ethidium bromide staining method. The procedure should prove valuable for the analysis of apoptosis in minute quantities of tissues and cultured cells. PMID- 8436603 TI - Stimulation of DNA synthesis and protooncogene expression in primary rat hepatocytes in long-term DMSO culture. AB - We have previously described the use of a chemically defined medium (CDM) supplemented with epidermal growth factor (EGF) and dimethylsulfoxide (DMSO) to maintain long-term cultures of rat hepatocytes in a highly differentiated state. In this study, conditions necessary to stimulate high levels of DNA synthesis in hepatocytes in long-term DMSO culture were defined. Hepatocytes were maintained in culture for 20 days in CDM containing DMSO and EGF, insulin, and glucagon. EGF, insulin, and glucagon were then removed for 7 days. Readdition of EGF, insulin, and glucagon at day 27 (shiftup) was accompanied by a three- to sixfold increase in labeling index. If DMSO or dexamethasone (dex) + DMSO were removed at time of shiftup, the labeling index increased by 18- to 54-fold. TGF beta inhibited DNA synthesis stimulated by EGF shiftup, TGF alpha shiftup, or EGF shiftup in combination with removal of dex + DMSO. Stimulation of DNA synthesis was accompanied by a specific, sequential induction of protooncogene mRNA levels; c-fos mRNA was induced 23-fold at 0.5 h after readdition of EGF; c-myc mRNA was induced three- to four-fold by 0.5 h; TGF alpha mRNA was induced sevenfold by 8 h; K-ras mRNA was induced fourfold by 26 h. Changes in protooncogene expression paralleled changes seen in regenerating liver. When DMSO was removed for greater than 48 h, the cells flattened and spread out, chords of cells were no longer well defined, albumin mRNA levels decreased, and fibronectin, beta 1 integrin, and TGF beta transcripts increased. PMID- 8436602 TI - Deregulation of granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor in murine macrophage cell line J774A.1. AB - J774A.1 immortalized macrophage tumor cells display several phenotypes and functional capacities similar to that of murine peritoneal exudate macrophages (PEM). Both populations display comparable number of M-CSF receptors. Yet the number of GM-CSF receptors on J774A.1 cells is only one-fourth that of PEM (1,500 vs. 6,000 per cell). Unlike J774A.1 cells, which constitutively express c-myc transcripts, normal PEM required rMuGM-CSF for the induction of c-myc expression. Nevertheless, the growth of J774A.1 cells can be further enhanced in the presence of exogenous rMuGM-CSF, rHuM-CSF, and rMuIL-3. Treatment with either rMuIL-3 (20 ng/ml) and rHuTGF-beta 1 (1.0 ng/ml) for 24 hr at 37 degrees C, markedly enhanced the expression of GM-CSF receptors on normal PEM but not leukemic J774A.1 cells. J774A.1 cells also did not respond by autologous upregulation of GM-CSF receptors as seen in PEM following treatment with rMuGM-CSF. Treatment with either pertussis toxin (20-100 ng/ml) or H-8 (50 microM) for 24 hr led to an enhanced expression of GM-CSF receptors on J774A.1 cells in a time- and dose-dependent manner but did not result in enhanced receptor expression on normal PEM. These findings suggest that the expression of GM-CSF receptors may be regulated by mechanisms involving Gi-proteins and their downstream elements, which in turn are linked to regulatory pathways of other cytokine receptors. In J774A.1 cells, such regulatory interaction may not exist. PMID- 8436604 TI - Ruffling and locomotion: role in cell resistance to growth factor-induced proliferation. AB - It has long been known that the growth rate of cells in vitro can be retarded by providing substrates of restricted area. Such experiments were performed with adhesive islets, made by depositing metals onto agarose layers through templates of various sizes. Since normal cells are unable to adhere to agarose, they become confined to the metallic surface. Using such haptotactic islets, we have studied the role of membrane ruffling and cell locomotion in the resistance of AG1523 human fibroblasts to growth factor-induced mitogenesis. Cells plated on small substrates, i.e., 2,150 microns 2 in area, initially showed vigorous ruffling, which was suppressed by 8 h after plating but had resumed again by 12 h. In contrast, cells on larger-size islets showed a rapid decline and stabilization of ruffling activity. When the growth rate was measured for single cells cultured on haptotactic islets, it was found to increase linearly from areas of 4,280 microns 2 up to 425,000 microns 2. Since the area needed to saturate the growth response was approximately 50-fold larger than the area occupied by a single cell, the growth inhibition was attributed in part to an interference with locomotion. The implication that locomotion provided positive input into growth control mechanisms was subjected to a direct test by evaluating the effect of nine polypeptide growth factors on the motility of serum-starved cells. All except TGF beta 1 stimulated movement. Finally, the mitogenic effect of growth factors was measured by [3H]thymidine incorporation and found to be proportional to motile activities, as quantitatively assayed. We conclude that locomotion suppression is a factor in AG1523 cell resistance to growth factor-induced mitogenesis. PMID- 8436605 TI - Rapid and reversible tubulin tyrosination in human neutrophils stimulated by the chemotactic peptide, fMet-Leu-Phe. AB - Neutrophil activation by specific stimuli, such as the oligopeptide chemotactic factor fMet-Leu-Phe (fMLF), is associated with an increased enzymatic addition of tyrosine to tubulin alpha-subunits, as measured by 14C tyrosine uptake. In studies using immunoblots we have found that this increased tyrosine uptake into tubulin in activated neutrophils reflects an increase in the proportion of cellular tubulin that is tyrosinated rather than simply an increase in the turnover of tyrosinated subunits. However, the increased accumulation of tyrosinated tubulin was also found to follow an initial depletion of tyrosinated tubulin and concomitant increase in detyrosinated tubulin between 0 and 60 sec following stimulation of neutrophils with fMLF. Immunogold electron microscopy studies of intact microtubules recovered from activated neutrophils demonstrated that these rapid changes in the relative content of tubulin isoforms in the cells were not associated with the formation or disappearance of microtubule microdomains composed of only one form of tubulin. Previously, we have shown that under conditions of fMLF-stimulated exocytosis there is an increased binding of neutrophil granules to endogenous microtubules. Since neutrophil activation by fMLF is associated with increased tyrosination of alpha-tubulin subunits, we speculated that rapid changes in the levels of tyrosinated tubulin in the microtubules of activated neutrophils might have a role in the regulation of granule-microtubule interactions. When the binding of purified neutrophil granules to reconstituted rat brain microtubules containing approximately 50% tyrosinated tubulin was measured by electron microscopy and compared with granule binding to microtubules that contained no detectable tyrosinated tubulin, granule microtubule associations were found to be significantly favored by detyrosinated vs. tyrosinated tubulin. These findings indicate that interactions between cytoplasmic granules and microtubules in activated neutrophils may be modulated by rapid changes in the relative content of detyrosinated and tyrosinated tubulin in the microtubule network of the cells. PMID- 8436606 TI - Regulation of fibronectin and laminin binding activity in cultured human lymphoblastic cell lines. AB - The current study shows that a clonal derivative of the Jurkat cell line up regulates both the avidity and density of the alpha 6/beta 1 receptor in response to phorbol 12-myristate 13-acetate (PMA). This derivative attaches to fibronectin and, to a lesser degree, laminin constitutively. Adhesion and spreading are dramatically up-regulated following treatment with PMA. The response on fibronectin peaks within 4 hours, is insensitive to cyclohexamide, can be blocked by monoclonal antibodies (Mabs) to the beta 1 and alpha 5 subunits of the beta 1 family of integrins, and is not associated with increased expression of the alpha 5 or beta 1 epitopes at the cell surface. In contrast, the response on laminin is biphasic. The early phase parallels the response on fibronectin. The second phase peaks after 48-72 hours of treatment with PMA, is sensitive to cycloheximide, can be blocked by Mabs to the beta 1 and alpha 6 subunits, and is associated with increased expression of the alpha 6 epitope. Both the density independent and dependent responses to PMA in Jurkat cells are blocked by the protein kinase inhibitor staurosporine. The HSB-2, CEM, Molt-4, and HPB-ALL T-lymphoblastic cell lines also up-regulate attachment to fibronectin and laminin following treatment with PMA. All four lines constitutively attach to fibronectin and show rapid up regulation of attachment following treatment with PMA. None of the lines attach to laminin prior to PMA treatment; however, specific adhesion developed after 4 120 hours of treatment. The most mature lines (Jurkat and HPB-ALL) up-regulated adhesion on laminin more rapidly than the less phenotypically mature lines (CEM, Molt-4, and HSB-2). In summary, clonal derivatives of the Jurkat cell line up regulated attachment to laminin through protein kinase dependent increases in alpha 6/beta 1 receptor avidity and density. In addition, the expression of functional receptors for laminin is linked to developmental maturity in a series of T-lymphoblastic cell lines. PMID- 8436607 TI - Occurrence and possible consequences of multipolar mitoses in primary cultures of adult rat hepatocytes. AB - Proliferating primary cultures of adult rat hepatocytes are characterized by the occurrence of multipolar mitoses, and chromosome loss resulting in the formation of micronuclei at telophase. The percentage of multipolar mitotic figures was determined to be 12.76 +/- 7.9%, 80% of which were tripolar. Multipolar mitotic stages showed a high incidence of chromosome loss, increasing from meta- (61.7 +/ 16.6%) to telophase (72.1 +/- 19.3%). Regular bipolar mitotic figures on the other hand also showed chromosome loss, however, to a lesser degree and decreasing from meta- (49.5 +/- 10.4%) to telophase (34.9 +/- 7.9%). The incidence of chromosome loss even in regular mitotic figures is very high compared to other cells and appears to depend on another special feature of hepatocytes: they remain flat and well attached during mitosis, so that shearing forces could be responsible for the separation of chromosomes from the mitotic spindle. Additionally this morphology creates a situation allowing for a maximal interaction of mitotic spindles of binucleated cells, leading to the high rate of multipolar mitoses observed. Both multipolar mitoses and chromosome loss could also explain the consecutive detachment of hepatocytes reported for proliferating primary cultures, since the aneuploid daughter cells generated can be expected to be non-viable in most cases and eventually detach. PMID- 8436608 TI - Intracellular signalling by nucleotide receptors in PC12 pheochromocytoma cells. AB - The effect of extracellular ATP was studied in PC12 cells, a neurosecretory line that releases ATP. The addition of micromolar concentrations of ATP to PC12 cells evoked a transient increase in the cytosolic free Ca2+ concentration ([Ca2+]i), as measured with the Ca(2+)-sensitive dye fura 2. AMP and adenosine were without effect, ruling out the involvement of P1 receptors in mediating this response. The increase in [Ca2+]i was reduced in calcium-free media and virtually eliminated by the addition of EGTA, suggesting that calcium influx was the primary response initiated by extracellular ATP. Nucleotide triphosphates such as UTP and, to a lesser degree, ITP also evoked an increase in [Ca2+]i while GTP and CTP had little effect. In order to identify the receptor subtype mediating this response, the efficacy of ATP and ATP cogeners was assessed. The rank order potency was ATP > adenosine 5'-[gamma-thio]triphosphate > ADP > 2 methylthioadenosine triphosphate (2-MeSATP) approximately adenosine 5'-[beta thio]diphosphate >> adenosine 5'-[alpha beta-methylene] triphosphate, adenosine 5'[beta gamma-imido]triphosphate. This profile is not characteristic of either the P2X or the conventional P2Y receptors. The Ca2+ response exhibited desensitization to ATP that was dependent on the extracellular metabolism of ATP. UTP was equally effective in desensitizing the response. ATP, UTP, ITP, and to a much lesser extent 2MeSATP increased inositol phosphate production in a dose dependent manner, suggesting receptor coupling to phosphatidylinositol-specific phospholipase C. These data are consistent with the view that PC12 cells express a class of non-P2Y nucleotide receptors (P2N) that mediate calcium influx and the accumulation of inositol phosphates. PMID- 8436609 TI - Regional changes in interstitial K+ and Ca2+ levels following cortical compression contusion trauma in rats. AB - Brain trauma is associated with acute functional impairment and neuronal injury. At present, it is unclear to what extent disturbances in ion homeostasis are involved in these changes. We used ion-selective microelectrodes to register interstitial potassium ([K+]e) and calcium ([Ca2+]e) concentrations in the brain cortex following cerebral compression contusion in the rat. The trauma was produced by dropping a 21 g weight from a height of 35 cm onto a piston that compressed the cortex 1.5 mm. Ion measurements were made in two different locations of the contused region: in the perimeter, i.e., the shear stress zone (region A), and in the center (region B). The trauma resulted in an immediate increase in [K+]e from a control level of 3 mM to a level > 60 mM in both regions, and a concomitant negative shift in DC potential. In both regions, there was a simultaneous, dramatic decrease in [Ca2+]e from a baseline of 1.1 mM to 0.3 0.1 mM. Interstitial [K+] and the DC potential normalized within 3 min after trauma. In region B, [Ca2+]e recovered to near control levels within 5 min after ictus. In region A, however, recovery of [Ca2+]e was significantly slower, with a return to near baseline values within 50 min after trauma. The prolonged lowering of [Ca2+]e in region A was associated with an inability to propagate cortical spreading depression, suggesting a profound functional disturbance. Histologic evaluation 72 h after trauma revealed that neuronal injury was confined exclusively to region A. The results indicate that compression contusion trauma produces a transient membrane depolarization associated with a pronounced cellular release of K+ and a massive Ca2+ entry into the intracellular compartment. We suggest that the acute functional impairment and the subsequent neuronal injury in region A is caused by the prolonged disturbance of cellular calcium homeostasis mediated by leaky membranes exposed to shear stress. PMID- 8436610 TI - Coupling of energy failure and dissipative K+ flux during ischemia: role of preischemic plasma glucose concentration. AB - The present experiments were undertaken to assess the influence of preischemic hypo- or hyperglycemia on the coupling among changes in extracellular K+ concentration (K+e) and in cellular energy state, as the latter is reflected in the tissue concentrations of phosphocreatine (PCr), Cr, ATP, ADP, and AMP, and in the calculated free ADP (ADPf) concentrations. The questions posed were whether the final release of K+ was delayed because the extra glucose accumulated by hyperglycemic animals produced enough ATP to continue supporting Na(+)-K(+) driven ATPase activity, and whether the additional acidosis altered the ionic transients. As expected, preischemic hypoglycemia shortened and hyperglycemia prolonged the phase before K+e rapidly increased. This was reflected in corresponding changes in tissue ATP content. Thus, hypoglycemia shortened and hyperglycemia prolonged the time before the fall in ATP concentration accelerated. When tissue was frozen at the moment of depolarization, the tissue contents of ATP were similar in hypo-, normo-, and hyperglycemic groups, approximately 30% of control. This suggests that hyperglycemia retards loss of ion homeostasis by leading to production of additional ATP. However, hyperglycemia did not reduce the rate at which the PCr concentration fell, and the ATP/ADPf ratio decreased. There were marked differences in the amount of lactate accumulated between the groups. Thus, massive depolarization in hypoglycemic groups occurred at a tissue lactate content of approximately 4 mM kg 1. This corresponds to a decrease in intracellular pH (pHi) from approximately 7.0 to approximately 6.9. In the hyperglycemic groups, depolarization occurred at a lactate content of about 12 mm kg-1, corresponding to a pHi of approximately 6.4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8436611 TI - Increases in interstitial adenosine and cerebral blood flow with inhibition of adenosine kinase and adenosine deaminase. AB - The purpose of this study was to determine the changes in interstitial fluid (ISF) adenosine and cerebral blood flow (CBF) during inhibition of adenosine kinase or adenosine deaminase. Brain microdialysis was used to (a) measure CBF (H2 clearance), (b) sample cerebral ISF, and (c) deliver drugs locally to the brain. Microdialysis probes were implanted bilaterally in the caudate nucleus of halothane-anesthetized rats (n = 11). One probe was perfused with artificial cerebrospinal fluid (CSF) containing iodotubercidin (IODO), an adenosine kinase inhibitor, while the other probe was perfused with erythro-2-(2-hydroxy-3 nonyl)adenine (EHNA), an adenosine deaminase inhibitor. Both probes were subsequently perfused with EHNA+IODO. Finally, 8-(p-sulfophenyl)theophylline (SPT), an adenosine receptor antagonist, was added to EHNA + IODO in one probe, while the other probe continued to receive only EHNA + IODO. CBF and dialysate adenosine levels increased with either EHNA or IODO; however, the increases were greater with IODO. EHNA + IODO further increased CBF and dialysate adenosine. The hyperemia observed with EHNA + IODO was abolished by adenosine receptor blockade. These data suggest that basal adenosine levels are influenced to a greater extent by adenosine kinase than by adenosine deaminase. In addition, the increased CBF observed with inhibition of adenosine metabolism and the attenuation of this vasodilatory response with adenosine receptor blockade support a role for adenosine in CBF regulation. PMID- 8436612 TI - Attenuation of ischemia-induced extracellular adenosine accumulation by homocysteine. AB - The purpose of this study was to determine the effects of homocysteine, which consumes intracellular adenosine via formation of S-adenosylhomocysteine, on interstitial fluid (ISF) adenosine and cerebral blood flow (CBF) before, during, and after cerebral ischemia. Microdialysis probes, used to measure local CBF (H2 clearance) and to sample ISF, were implanted bilaterally into the caudate nucleus of halothane-anesthetized rats (n = 8). L-Homocysteine thiolactone was administered locally via one of the probes. Animals were exposed to 20 min of ischemia, induced by bilateral carotid occlusion plus hemorrhage to an arterial blood pressure of 50 mm Hg, followed by 60 min of reperfusion. Before ischemia, CBF and dialysate adenosine were decreased with homocysteine. During ischemia and early reperfusion, dialysate purine metabolites increased on both sides of the brain; however, the ischemia-induced increase in adenosine was attenuated on the side of local homocysteine. CBF was lower on the side of homocysteine throughout reperfusion. These data demonstrate that homocysteine (a) decreases basal ISF adenosine and CBF, (b) attenuates the increase in dialysate adenosine during ischemia, and (c) reduces hyperemia during early reperfusion. PMID- 8436613 TI - Changes in pial arteriolar diameter and CSF adenosine concentrations during hypoxia. AB - We measured the changes in pial arteriolar diameter and CSF concentrations of adenosine, inosine, and hypoxanthine during hypoxia in the absence and presence of topically applied dipyridamole (10(-6) M) and erythro-9-(2-hydroxy-3 nonyl)adenine (EHNA; 10(-5) M). Closed cranial windows were implanted in halothane-anesthetized adult male Sprague-Dawley rats for the observation of the pial circulation and collection of CSF. The mean resting arteriolar diameter in mock CSF was 31.2 +/- 5.9 microns. Topically applied dipyridamole and EHNA, in combination, caused a slight but significant (p < 0.05) increase in resting arteriolar diameter (33.8 +/- 4.3 microns). With mock CSF, moderate hypoxia caused a 22.1 +/- 9.7% increase in pial vessel diameter. Topically applied dipyridamole and EHNA significantly (p < 0.01) potentiated pial arteriolar vasodilation in response to hypoxia. Moreover, the potentiating effects of dipyridamole and EHNA during hypoxia were completely abolished by theophylline (0.20 mumol/g, i.p.; p < 0.05), an adenosine receptor antagonist. Resting concentrations of adenosine, inosine, and hypoxanthine in the subwindow CSF were 0.18 +/- 0.09, 0.35 +/- 0.21, and 0.62 +/- 0.12 microM, respectively. In the absence of dipyridamole and EHNA, these levels were not affected by sustained moderate hypoxia (PaO2 = 36 +/- 6 mm Hg). However, in the presence of dipyridamole and EHNA, the concentration of adenosine in the CSF during hypoxia was significantly (p < 0.05) increased. Our data indicate that dipyridamole and EHNA potentiate hypoxic vasodilation of pial arterioles while simultaneously increasing extracellular adenosine levels, thus supporting the hypothesis that adenosine is involved in the regulation of cerebral blood flow. PMID- 8436614 TI - Basic fibroblast growth factor protects against hypoxia-ischemia and NMDA neurotoxicity in neonatal rats. AB - Basic fibroblast growth factor (bFGF) is a polypeptide that promotes neuronal survival and blocks excitatory amino acid (EAA) neurotoxicity in vitro at very low concentrations. In the present study, we examined whether systemically administered bFGF could prevent neuronal damage induced by either EAAs or hypoxia ischemia in vivo. Neuroprotective effects were examined in a neonatal model of hypoxia-ischemia (unilateral ligation of the carotid artery followed by exposure to 8% oxygen for 1.5 h) and following intrastriatal injection of N-methyl-D aspartate (NMDA) in 7-day-old rats. Intraperitoneal administration of a single dose of bFGF (50-300 micrograms/kg) 30 min before intrastriatal injection of NMDA showed a dose-dependent neuroprotective effect. Repeated doses of bFGF (100 micrograms/kg) both before and after intrastriatal NMDA injection produced a much greater significant protective effect than a single dose administered prior to the injection. Intraperitoneal injection of single dose of 100 micrograms/kg of bFGF 30 min before hypoxia-ischemia reduced neuronal damage by 38% (p = 0.14), while administration of bFGF at a dose of 100 micrograms/kg i.p. three times, 30 min before and 0 and 30 min after hypoxia-ischemia, significantly reduced neuronal damage by 64% (p = 0.004). Systemic administration of bFGF did not change body temperature for up to 3 h. These results show that systemic administration of bFGF can exert neuroprotective effects against both NMDA induced excitotoxicity and hypoxia-ischemia in vivo. PMID- 8436615 TI - Energy reserves and utilization rates in developing brain measured in vivo by 31P and 1H nuclear magnetic resonance spectroscopy. AB - Age-related changes in cerebral energy utilization were examined in swine, a species whose maximal rate of development is known to occur in the perinatal period. Interleaved in vivo 31P and 1H nuclear magnetic resonance spectroscopy was used to measure the rates of change in cerebral concentrations of phosphocreatine (PCr), nucleoside triphosphates, and lactate following complete ischemia, induced via cardiac arrest, in a total of 19 newborn, 10-day-old, and 1 month-old piglets. Preischemic concentrations of these three metabolites plus glucose and glycogen were determined in a separate experiment on 12 piglets whose brains were funnel-frozen in situ. The rate constants for the PCr and ATP decline and lactate increase were determined by nonlinear regression fits to the experimental data, assuming first-order kinetics. The rate constants and preischemic metabolite concentrations were used to calculate the initial flux of high-energy phosphate equivalents (approximately P), which was used as an estimate of cerebral energy utilization at the point when ischemia was initiated. Cerebral energy utilization equaled 6.5 +/- 1.9, 9.5 +/- 3.2, and 15.1 +/- 3.2 mumol approximately P/g/min in newborn, 10-day-old, and 1-month-old piglets, respectively. Within each age group the energy utilization rate was not altered by hyperglycemia-induced increases in cerebral energy reserves, but during hypoglycemia cerebral energy utilization rates decrease. The slope of approximately P versus time decreased with the duration of ischemia, indicating that cerebral energy utilization rates decrease after the first few minutes of ischemia. Newborn piglets had higher cerebral energy utilization rates compared with literature values for newborn rats and mice. This is consistent with the concept that newborns from a species with a perinatal stage of maximal growth and development will have higher cerebral energy demands compared with newborns from a species such as rodents, whose maximal growth occurs postnatally. However, this conclusion remains tentative because literature cerebral utilization rates estimated from the initial slope of approximately P-versus-time plots tend to underestimate the true rate, since the assumption of continued linearity may not be valid for the interval chosen. PMID- 8436616 TI - Role of protein kinase C in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage. AB - This study investigated the role of protein kinase C (PKC) in the pathogenesis of vasospasm after experimental subarachnoid hemorrhage (SAH). PKC activation by intracisternal injection of a phorbol ester [12-O-tetradecanoylphorbol-13-acetate (TP)] induced dose-dependent, slowly developing, severe contraction of the basilar artery. A single intracisternal injection of TP (5 x 10(-9) M in the CSF) induced sustained contraction lasting over 3 days, which almost paralleled the changes of membrane-bound PKC activity in the basilar arterial wall. In a two hemorrhage SAH model, membrane-bound PKC activity in the basilar artery increased up to day 4 and returned to the control level by day 14, whereas angiographic contraction reached a maximum on day 7 and still persisted at a moderate level on day 14. Thus, there was a discrepancy between arterial PKC activity and arterial contraction. Multiple intracisternal injections of TP produced 30-40% sustained contraction of the basilar artery lasting for more than 10 days along with sustained activation of PKC to levels compatible with that observed in the SAH model. However, TP injection caused considerably milder histological changes in the basilar artery than those noted in the SAH model. We concluded that cerebral vasospasm after SAH cannot be explained solely on the basis of activation of the PKC pathway. PMID- 8436617 TI - Cerebral vascular autoregulation and CO2 reactivity following onset of the delayed postischemic hypoperfusion state in dogs. AB - A small number of animal studies have suggested that during the delayed postischemic hypoperfusion state, CO2 reactivity of the cerebral vasculature is lost whereas autoregulation is retained. These findings, however, are inconsistent with the bulk of experimental evidence which demonstrates that CO2 reactivity is more robust and may be retained in pathologic circumstances which abolish autoregulation. These opposing viewpoints were therefore further evaluated in 18 dogs in which complete global ischemia was induced by cerebrospinal fluid (CSF) compression for periods of 12 (n = 12) and 18 (n = 6) min. Following 45 min of reperfusion and with onset of the delayed postischemic hypoperfusion state, autoregulation and CO2 reactivity were evaluated using a continuous measurement of CBF (by sagittal sinus outflow). CO2 reactivity was tested over a PaCO2 range of 20 to 60 mm Hg; autoregulation was tested over a blood pressure range of 60 to 140 mm Hg. Results demonstrated that after both 12 and 18 min of complete global ischemia, autoregulation and CO2 reactivity of the cerebral vasculature were both present, but attenuated. In the case of CO2 reactivity, the slope of the CBF response was decreased approximately 75%. In the case of autoregulation, the response in some dogs was incomplete as compared with their preischemic response. PMID- 8436618 TI - Effect of cervical sympathectomy and hypoxia on the heterogeneity of O2 saturation of small cerebrocortical veins. AB - This study evaluated the hypothesis that the sympathetic nervous system was one of the factors increasing the heterogeneity of cerebrocortical venous O2 saturation and this heterogeneity would be greater during hypoxia when cervical sympathetic activity was elevated. Thirty-two male Long-Evans rats were either sham operated (n = 16) or received bilateral cervical sympathectomy (n = 16). One half of the animals (n = 8) in each treatment were challenged by hypoxia (8% O2 in N2). Cerebral blood flow was determined in five brain regions with [14C]iodoantipyrine. Oxygen saturation was measured microspectrophotometrically in small cerebrocortical arteries and veins. The degree of hypoxic hyperemia was not significantly different between sham-operated and sympathectomized rats. Cortical venous O2 saturations, indicating the balance between O2 supply and consumption, were significantly more heterogeneous in the sham-operated group under both normoxic and hypoxic conditions. The coefficient of variation (CV = 100 x SD/mean) for the normoxic sham-operated animals was 24.9% and the average venous O2 saturation was 53.8%. During hypoxia, venous O2 saturation was significantly decreased to 43.1% without a change in CV (24.5%). Sympathectomy significantly reduced this heterogeneity through a reduction in the number of low O2 saturation veins (CV = 13.2%) under normoxic conditions and the effect was similar under hypoxic conditions (CV = 15.3%). In both sham-operated and sympathectomized groups, hypoxia elicited a significantly higher cerebrocortical O2 consumption. Thus, bilateral cervical sympathectomy improved the O2 supply in selective cerebrocortical regions with high O2 extraction. However, the effect of sympathetic innervation on the heterogeneity of cerebrocortical venous O2 saturation was not potentiated by hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8436619 TI - Endothelin-1-induced reductions in cerebral blood flow: dose dependency, time course, and neuropathological consequences. AB - The capacity of endothelin-1 to induce severe reductions in cerebral blood flow and ischaemic neuronal damage was assessed in anaesthetised rats. Endothelin-1 (25 microliters of 10(-7)-10(-4) M) was applied to the adventitial surface of an exposed middle cerebral artery and striatal blood flow assessed by the hydrogen clearance technique. Endothelin-1 induced severe dose-dependent reductions in cerebral blood flow (e.g., minimum CBF at 10(-5) M of 9 +/- 11 ml 100 g-1 min-1 compared to 104 +/- 22 ml 100 g-1 min-1 with vehicle, p < 0.05), which persisted for at least 60 min at each concentration of endothelin-1. Application of endothelin-1 to the middle cerebral artery produced dose-dependent ischaemic brain damage (e.g., volume of damage of 65 +/- 34 mm3 at 10(-5) M compared to 0.22 +/- 0.57 mm3 for vehicle, p < 0.01). These data demonstrate that endothelin 1 is capable of reducing blood flow to pathologically low levels and provide a new model of controlled focal ischaemia followed by reperfusion. PMID- 8436620 TI - Role of nitric oxide in the cerebral vasodilatory responses to vasopressin and oxytocin in dogs. AB - We angiographically assessed the vasodilatory effects of vasopressin and oxytocin on the basilar arteries in dogs. Intracisternal bolus injections of vasopressin (100 pmol and 1 nmol) and oxytocin (1 and 10 nmol) produced dose-dependent increases in the internal diameter of the basilar arteries without affecting mean arterial blood pressure. The maximal dilatations of the basilar arteries induced by 1 nmol vasopressin and 10 nmol oxytocin were 142.3 +/- 19.9 and 136.8 +/- 25.5% of the baseline, respectively. When the same peptides were injected into the vertebral artery, the maximal dilatations were similar, but the duration of response was shorter. Pretreatment with intracisternal injection of 10 mumol NG monomethyl-L-arginine (L-NMMA), which inhibits the synthesis of nitric oxide from L-arginine, suppressed the vasodilatory responses induced by intracisternal injection of vasopressin and oxytocin and by intraarterial injection of vasopressin. Calcitonin gene-related peptide also caused dilatation of the basilar artery when injected into the cisterna magna, but its effect was not blocked by L-NMMA. L-NMMA reduced the basal diameter of the basilar artery in a dose-dependent manner; L-arginine produced dose-dependent increases in diameter. The vasoconstriction induced by L-NMMA was reversed by high concentrations of L arginine. These results suggest that vasopressin and oxytocin dilate the basilar arteries via the release of nitric oxide from both the intraluminal and the extraluminal sides and that synthesis and release of nitric oxide in the vascular wall contribute to maintenance of basal vascular tonus. PMID- 8436621 TI - PACAP, a VIP-like peptide: immunohistochemical localization and effect upon cat pial arteries and cerebral blood flow. AB - Pituitary adenylate cyclase activating peptide (PACAP) is a vasoactive intestinal polypeptide (VIP)-like peptide recently isolated from ovine hypothalami. Nerve fibers containing PACAP immunoreactivity were present in the adventitia and the adventitia-media border of cat cerebral arteries. Double immunostaining revealed that PACAP-immunoreactive nerve fibers constituted a subpopulation of the VIP containing fibers. PACAP effected a concentration-dependent relaxation of feline middle cerebral arteries that had been precontracted with prostaglandin F2 alpha. The maximum relaxation, 24 and 34% of precontraction, was achieved with PACAP-38 and PACAP-27, respectively, at a concentration of 10(-6) M. In cats anesthetized with alpha-chloralose, intracerebral microinjection of PACAP effected a moderate increase in cerebral blood flow. The maximal increase (18.6 +/- 6%) was observed following the injection of 5 micrograms PACAP. PMID- 8436622 TI - Nonpeptide angiotensin AT1 and AT2 receptor ligands modulate the upper limit of cerebral blood flow autoregulation in rats. AB - We investigated the effect of angiotensin AT1 and AT2 receptor blockade on the upper limit of CBF autoregulation in pentobarbital-anesthetized rats. CBF was measured by laser-Doppler flowmetry from the parietal cortex and MABP was increased by intravenous phenylephrine infusion. Neither the AT1 antagonist losartan nor the AT2 ligand PD 123319 nor angiotensin II (ANG II) in the presence of losartan affected baseline CBF. When the blood pressure was increased in the control group, CBF remained fairly constant up to 145 mm Hg and increased steeply after 150 mm Hg. Both PD 123319 (7-10 mg/kg) and losartan (1-10 mg/kg) shifted the upper limit of CBF autoregulation toward higher pressures. Intravenous infusion of PD 123319 was more effective than bolus injection. The losartan effect was dose dependent. Selective stimulation of AT2 receptors with an intravenous ANG II infusion (0.54 micrograms/min) in the presence of losartan did not reverse the effect of losartan on CBF autoregulation, but, on the contrary, appeared to further shift the upper limit of autoregulation toward higher pressures. The results implicate a role for both AT1 and AT2 angiotensin receptors in the regulation of CBF. PMID- 8436623 TI - Triphasic response of rat intracerebral arterioles to increasing concentrations of vasopressin in vitro. AB - To determine how vasopressin affects the vascular tone of the smaller cerebral arterioles, we carried out an in vitro study of isolated and cannulated intracerebral arterioles of rats. We found that increasing concentrations of vasopressin induced a triphasic response of vasodilation (10(-12)-10(-11) M), vasoconstriction (10(-10)-10(-8) M), and vasodilation stabilizing to control diameter (10(-7)-10(-6) M) and that the maximum constriction was twice the maximum dilation in these smaller arterioles [21.2 +/- 13.1% (mean +/- SD) decrease in diameter vs. 11.2 +/- 5.7% increased]. Pretreatment of the arterioles with NG-monomethyl-L-arginine (10(-4) M), a specific inhibitor of endothelium derived relaxing factor, abolished the vasopressin-induced vasodilation and significantly increased the vasoconstriction. These results suggest that these arterioles were maintained in a dilated state by an endothelium-derived relaxing factor activated by vasopressin. Both vasodilation and vasoconstriction were found to be mediated through vasopressin V1 receptors in a study of arterioles pretreated with d(CH2)5Tyr(Me)arginine vasopressin (10(-6) M), a vasopressin V1 receptor antagonist. These results support the hypothesis that vasopressin may constrict smaller cerebral arterioles while simultaneously dilating larger cerebral arteries. Our results also suggest that vasopressin may aggravate cerebral ischemia in pathological conditions, such as subarachnoid hemorrhage, when the arteriolar response to vasopressin shifts from vasodilation to vasoconstriction due to increased vasopressin levels in plasma and CSF and impaired endothelium-derived relaxation. PMID- 8436624 TI - Decrease in human striatal dopamine D2 receptor density with age: a PET study with [11C]raclopride. AB - The effect of age on human striatal dopamine D2 receptors was investigated with positron emission tomography (PET) using [11C]raclopride as a radioligand. Twenty one healthy volunteers aged from 20 to 81 years were studied. An equilibrium method was applied and two separate PET scans with different specific activities of [11C]raclopride were performed. The maximal number of receptors (Bmax) and their dissociation constant (Kd) were calculated using Scatchard analysis. There was an age-dependent decline in the Bmax (r = -0.49; p = 0.02) of striatal D2 receptors while the Kd remained unchanged. The results show that there is an age related loss of striatal D2 receptors, which, together with other changes in the brain nigrostriatal dopaminergic system, may contribute to extrapyramidal symptoms associated with aging. PMID- 8436625 TI - Metabolites of 2-deoxy-[14C]glucose in plasma and brain: influence on rate of glucose utilization determined with deoxyglucose method in rat brain. AB - The [14C]deoxyglucose ([14C]DG) method depends upon quantitative trapping of metabolites in brain at the site of phosphorylation, and in the usual procedure it is assumed that all the label in plasma is in free DG. Our previous finding of labeled nonacidic derivatives of DG in plasma raised the possibility that some metabolites of DG might not be fully retained in body tissues and therefore cause overestimation of the integrated specific activity of the precursor pool determined from assay of label in plasma and/or underestimation of the true size of the metabolite fraction in brain. In the present study, metabolism of DG in rat tissues by secondary pathways was examined and found to be more extensive than previously recognized. When 14C-labeled compounds in ethanol extracts of either plasma or brain were separated by anion exchange HPLC, eight fractions were obtained. 14C-labeled metabolites in plasma were detected after a 35-min lag and gradually increased in amount with time after an intravenous pulse. In brain, deoxyglucose-6-phosphate was further metabolized, mainly to deoxyglucose-1 phosphate and deoxyglucose-1,6-phosphate. These are acid-labile compounds and accounted for approximately 20% of the 14C in the metabolite pool in brain. The rate constants for net loss of 14C from the metabolite pool between 45 and 180 min after a pulse were similar (0.4-0.5%/min) in vivo and in intact postmortem brain. The rate constant for loss of deoxyglucose-6-phosphate (DG-6-P) in vivo (approximately 0.7%/min) was, however, about twice that for postmortem brain, suggesting that a significant fraction of the DG-6-P lost in vivo is due to its further metabolism by energy-dependent reactions. 14C-labeled metabolites of [14C]DG in plasma and brain do not interfere with determination of local rates of glucose utilization in brain in normal, conscious rats by the autoradiographic method if the prescribed procedures and a 45-min experimental period are used. PMID- 8436626 TI - Microwave fixation for the determination of cerebral blood volume in rats. AB - The cerebral blood volume (CBV) is sensitive to changing hydrostatic pressures. Thus, measurement methods that rely on removing tissue from unfixed brain may lead to underestimates of the CBV due to the loss of blood from the tissue. In situ fixation of tissue before removal may offer improved accuracy. We employed a triple-label method to measure simultaneously whole brain CBF and CBV in halothane-anesthetized Sprague-Dawley rats, which were then killed either by focused microwave irradiation (approximately 8 kW of incident power x 770 ms) or by decapitation. CBF was measured with [3H]nicotine while the CBV was determined as the sum of the cerebral red cell volume (CRCV--measured with 99mTc-labeled red cells) and the cerebral plasma volume (CPV--measured with [14C]dextran). Animals were studied during hypocarbic (PaCO2 approximately 25 mm Hg), normocarbic, or hypercarbic (PaCO2 approximately 70 mm Hg) conditions. Added studies were performed to verify that the microwave irradiation scheme used was capable of fixing previously administered tracers in place, and also halting the entry of tracer given after irradiation. Results indicate that the method of killing had no effects on CBF measurements, as assessed either by absolute values during normocarbia or responsiveness to changing PaCO2. However, all three volume measurements made using nondiffusible tracers (CRCV, CPV, and CBV) were significantly lower in animals killed by decapitation. Furthermore, CO2 responsiveness for all three variables (as assessed by the slope of the PaCO2/volume) was not evident in decapitated animals. We conclude that in situ fixation offers significant advantages when examining the cerebral distribution space of nondiffusible tracers. PMID- 8436627 TI - Glucose transporter isoforms in brain: absence of GLUT3 from the blood-brain barrier. AB - Two glucose transporter (GLUT) isoforms have been identified in brain. The GLUT1 isoform is abundant in cerebral microvessels and may be present in glia and neurons, whereas GLUT3 is probably the major neuronal glucose transporter. This study investigates whether GLUT3 is also present in microvessels from rat, human, and canine brain, by means of antisera directed against the divergent C-terminal sequences of mouse and human GLUT3. GLUT1 was detected in whole brain as two molecular mass forms: 55 kDa in microvessels and 45 kDa in cortical neuronal/glial membranes. With the aid of the appropriate antisera to the species specific sequences, GLUT3 was detected in rat and human cortical membranes but not in isolated rat or human microvessels. These antisera failed to detect GLUT3 in either canine cortical membranes or canine microvessels, implying additional species specificity in the C-terminal sequence. PMID- 8436628 TI - Topical application of fluorides on teeth. New concepts of mechanisms of interaction. AB - Prevention of caries in exposed root surfaces constitutes an important clinical problem. It is thus important that clinicians involved with periodontology have an insight into fluoride prophylaxis. The understanding of the cariostatic mechanism of fluoride has improved during recent years. The aim of the present review is to give a short account of the present concept. Calcium fluoride appears to be the only product which is formed on enamel, dentin or cementum during brief topical treatments with fluoride or use of toothpaste containing fluoride. This calcium fluoride is stable in the oral environment; this is contrary to what was believed until recently. The calcium fluoride constitutes a pH-dependent reservoir of fluoride which releases fluoride when pH drops. The practical consequences of this concept is discussed. PMID- 8436629 TI - Epithelial remnants in the crestal periodontium of the dog. AB - The purpose of this study was to access the effect of age on the epithelial remnants (EPRs) of the crestal periodontal tissues of beagle dogs. The material consisted of 10 beagle dogs; 5 were 1-year-old (young dogs) and 5 were 9-years old (old dogs). All animals belonged to the same dog colony and had been raised under similar conditions. Since birth, the dogs had been subjected to professional prophylaxis 4x /per year. Biopsies were obtained from the mandibular 3rd and 4th premolar regions and were prepared for histologic analysis. 2 areas, (1) the supracrestal region and (2) the marginal periodontal ligament region, were identified. The supracrestal region was further divided into 4 compartments of equal height. The histologic parameters studied included: the (i) number of EPRs/mm root length; EPR frequency; (ii) size of EPR; (iii) distance between the root surface and the EPR; (iv) distance between the alveolar bone and the EPR; (v) epithelial cell area. The supracrestal region (total and various compartments) of old dogs harbored significantly fewer yet larger EPRs than epithelial remnants of young dogs. Similarly, the EPR's of the periodontal ligament region were significantly larger and closer to the root surface in old dogs compared to young dogs. No difference was noted in the cell area of EPRs between young and old dogs for either region. Epithelial remnants of the supracrestal region in both groups of dogs were somewhat more frequent, larger and positioned further from the root surface than the EPRs of the periodontal ligament region.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8436630 TI - Relationship between periapical and periodontal status. A clinical retrospective study. AB - The purpose of the present investigation was to explore possible relationships between clinical periodontal status in periodontally involved teeth with and without endodontic infection. The investigation was conducted as a retrospective study on a consecutive referral population. The periapical conditions in endodontically-involved single-rooted teeth from a selected patient sample were evaluated and correlated to their periodontal status. There was a significant correlation between periapical pathology and vertical bony destructions. An intra individual comparison between pocket depth in teeth with and without periapical pathology showed that periapical pathology was significantly correlated to an increased pocket depth in the absence of a vertical bony destruction. It was concluded that an endodontic infection, evident as a periapical radiolucency, promotes periodontal pocket-formation on an instrumented marginal root surface and, consequently, should be regarded as a risk factor in periodontitis progression and be given appropriate consideration in periodontal treatment planning. PMID- 8436631 TI - Root caries susceptibility in periodontally treated patients. Results after 12 years. AB - The aim of the investigation was to study the individual susceptibility to root caries in periodontally treated patients in a long-term follow-up of 12 years. Age, plaque score, salivary counts of lactobacilli and mutans streptococci, salivary secretion rate and buffer effect, oral sugar clearance time and dietary habit index were tested as possible predictors for root caries incidence. During the whole observation period of 12 years, new root caries lesions were recorded in 24 of a total of 27 patients. In 8 of these, the root caries incidence was between 1 and 5, in 7 between 6 and 9 and in 9, 12 or more new DFS. However, the annual mean number of new DFS was rather low. 13 patients with > 5 new DFS% during the 3rd 4-year period (years 9-12) differed significantly from 14 patients with < or = 5 new DFS% in salivary mutans streptococcus counts (p < 0.01), plaque scores (p < 0.001) and new DFS% during the 2nd 4-year period (years 5-8) (p < 0.001). Simultaneously, risk values among the variables tested at the 8-year examination were about 3 x more prevalent in patients that developed > 5 new DFS% in years 9-12 than in those with < or = 5 new DFS%. During the whole 12-year observation period, smokers had significantly more root caries than non-smokers (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8436632 TI - A 6-month home usage trial of a 1% chlorhexidine toothpaste (1). Effects on plaque, gingivitis, calculus and toothstaining. AB - Research and development has been aimed towards the development of toothpastes for oral hygiene and gingival health benefits. The most effective antiplaque agent to date, chlorhexidine, is difficult to formulate into active toothpaste products. Despite some encouraging findings for experimental chlorhexidine toothpastes, there are to date no commercially available products. Based on positive findings from an experimental gingivitis study, this investigation evaluated 2 chlorhexidine toothpastes, one with fluoride, as adjuncts to oral hygiene. The study was a double-blind controlled, parallel, balanced group design, extending over 6 months. A total of 297 volunteers commenced the study after screening for a minimum acceptance level of gingivitis. At baseline, 6, 12 and 24 weeks, stain, gingival, bleeding and plaque indices were recorded, together with a calculus index at 6, 12 and 24 weeks. After a baseline prophylaxis, volunteers used the allocated product 2 x per day, with no other oral hygiene instructions given. Plaque, gingival and bleeding scores improved in all 3 groups, but to an overall significantly greater extent in the active groups. However, staining and calculus indices were significantly increased in the active compared to the control group. If the local side-effects of chlorhexidine are considered to be acceptable, these chlorhexidine toothpastes could be recommended for the same clinical applications as other chlorhexidine products. The apparent compatibility of fluoride with chlorhexidine in the one product may be pertinent to caries prevention. PMID- 8436633 TI - Relationship of "bleeding on probing" and "gingival index bleeding" as clinical parameters of gingival inflammation. AB - Bleeding on probing (BOP) and the gingival index have been used to clinically characterize the degree of gingival inflammation. It is, however, unclear to what extent these parameters correlate to each other and to probing pocket depth (PD). The purpose of this clinical study was to evaluate the association between BOP and GI bleeding (scores of 2 and 3), as well as the relationship of these variables to PD, in a group of patients presenting with naturally-occurring gingivitis. Based on screening examinations of 125 subjects with at least 20 teeth, no more than 4 sites with PD over 6 mm, a BOP frequency of 30% or greater, and no systemic condition that would influence the inflammatory response, were selected. 2 weeks after screening they were examined at 6 sites per tooth for plaque index, GI, PD and BOP. A standardized pressure sensitive probe (Florida Probe) with 20 g probing force was used for BOP and PD measurements. In this population, means of 40.9% (S.E. = 1.36) BOP sites and 35.3% (S.E. = 1.81) GI bleeding sites per patient were found. A total of 20,008 sites ranging in PD up to 5.9 mm were evaluated; however, the majority of sites (19,723, 98.6%) presented with < 4 mm PD. When sites were evaluated, BOP demonstrated a positive correlation with PD, whereas GI bleeding correlated with PD. For sites characterized by the absence of BOP as well as the absence of GI bleeding (scores 0 and 1), the highest % of agreement between the 2 indices (77.7%) was found in shallow sites (0.1-2 mm).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8436634 TI - Utility of Ramfjord index teeth to assess periodontal disease progression in longitudinal studies. AB - The feasibility of using the Ramfjord index teeth to estimate whole-mouth periodontal disease activity was investigated. Whole-mouth examinations were carried out semi-annually over a 36-month period in 98 maintenance patients previously treated for adult periodontitis. Recurrent periodontitis was defined as either a 3-mm or greater probing depth increase from baseline, or a 2-mm or greater probing depth increase together with 2-mm or greater of relative attachment loss measured from a reference stent. Whole-mouth disease activity was compared to Ramfjord index teeth data, with and without adjustment. Adjustment was made by multiplying disease activity rates on Ramfjord index teeth by the ratio formed from the sum of all teeth present over the sum of all Ramfjord index teeth in the study population. Without adjustment, Ramfjord index teeth markedly underestimated subjects with recurrent disease activity when compared to whole mouth findings. However, with adjustment, the hypothesis that upper and lower limits on whole-mouth incidence of recurrent periodontitis could be estimated from Ramfjord index teeth disease-activity rates were not rejected (P > 0.20, z test) at any 6-month interval. At 5 of 6 examinations, the % of disease active subjects as determined from whole-mouth evaluations was below the upper limit for disease incidence calculated, with 95% confidence, from point estimates derived from adjusted Ramfjord index teeth data. Partial-mouth examinations with appropriate adjustment of Ramfjord index teeth data may be useful for assessing periodontal disease progression in longitudinal population studies of human periodontitis. PMID- 8436635 TI - Relative effectiveness of various alternating frequencies of a power toothbrush. AB - The influence on plaque-removing efficiency of the alternating frequency of a powered brush has never been established. In the present study, a mechanical brush was tested at various alternations per minute (F1 = 2100, F2 = 2500, F3 = 3500). A double-blind, randomized, triple crossover design was applied. After a plaque growth phase, the test brushes were used under supervision for 90 s and the remaining plaque scored. A ridit analysis yielded significant differences between F2 and F1/F3. Odds ratios and frequency distributions demonstrated a clinically meaningful advantage for F2. Subjective evaluation by the participants confirmed the positive performance of F2. The results can be generalized in 3 ways: (1) the alternating frequency of a power brush influences its effectiveness, (2) high frequencies are not generally superior, (3) the test brush has its optimal cleaning efficiency at F2, which does not necessarily need to be true for other brands. It seems imperative to determine the optimal frequency for any new brush in a controlled study. PMID- 8436636 TI - Alternative methods for screening periodontal disease in adults. AB - Clinical measurements of periodontal attachment loss, while not always representing the histological changes, are used to establish the diagnosis of adult periodontitis. Such measurements are difficult to perform accurately and are labor intensive. To counter these problems, index teeth and index sites have been employed in an attempt to estimate the severity of the periodontal condition without the need to resort to elaborate attachment measurements. Unfortunately, such indices usually tend to underestimate prevalence while often overestimating severity. The purpose of the present study was to examine the correlation of alternative clinical, radiographic and microbiological parameters, with periodontal disease using the diagnostic criteria of established periodontitis. 508 adults included in this study received thorough periodontal examination which included probing pocket depth, clinical attachment level, plaque, gingival and calculus scores, together with radiographic analysis and assays of subgingival periopathogenic microorganisms. Radiographic alveolar bone loss and probing pocket depth had the highest correlation with clinical attachment loss (phi = 0.72 and phi = 0.75 respectively). Plaque scores (phi = 0.17), like gingival scores (phi = 0.06) and calculus scores (phi = 0.42) had poor correlation with established periodontitis. Periodontopathogenic species demonstrated high specificity and negative predictive values; but low sensitivity and positive predictive values make for an overall low correlation of these species with established periodontitis. However, when used in a logistic regression model, the presence of P. gingivalis (odds ratio = 6.25) has shown to contribute significantly to the estimate of probability for established periodontitis. The use of these various alternative parameters for screening of periodontal disease is discussed in light of their sensitivity, specificity and predictive value. PMID- 8436637 TI - Topical application of tetracycline-HCl in human periodontitis. AB - Previous in vitro studies have suggested that tetracycline-HCl (TTC-HCl) is adsorbed and actively released from root dentin. The aim of the current study was to evaluate the binding to and release of TTC-HCl from human root dentin surfaces in vivo, and to evaluate the clinical utility of TTC-HCl irrigation as an adjunct to scaling and root planing. Experiment I utilized two contralateral mandibular single-rooted teeth which were examined in four adults with severe generalized periodontitis. One tooth in each patient was carefully scaled and root planed, under local anesthesia, and the other used as an unscaled control. Each subgingival root surface was irrigated for 5 min with an aqueous TTC-HCl solution at a concentration of 100 mg/ml. Gingival crevicular fluid samples were collected on paper strips for the next three weeks. The TTC-HCl concentrations in each sample were determined by the inhibition zone of B. cereus cultured on agar plates. The TTC-HCl concentrations in gingival crevicular fluid collected 15 min after irrigation were 3100 +/- 670 micrograms/ml from the scaled lesions and 4700 +/- 1300 micrograms/ml from the unscaled root surfaces. The antibiotic concentrations decreased logarithmically over the next 7 days; 1500 +/- 270 micrograms/ml and 1100 +/- 330 micrograms/ml at 2 h, 880 +/- 350 micrograms/ml and 1300 +/- 360 micrograms/ml at 6 h and 19 +/- 5 micrograms/ml and 31 +/- 26 micrograms/ml at 1 week for scaled and unscaled root surfaces, respectively. Results for week two and three indicated an average of over 8 micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8436638 TI - Metronidazole in periodontitis (IV). The effect of patient compliance on treatment parameters. AB - Patient compliance with the unsupervised usage of prescription medication can be poor. In the treatment of periodontal infections with systemic antimicrobial agents, in situations where the efficacy of the antimicrobial agent is being evaluated, non-compliance could underestimate the true efficacy of the agent. Metronidazole is an agent with reported success in the treatment of anaerobic periodontal infections. Metronidazole is particularly effective in vitro against spirochetes, and this efficacy was investigated as a means of measuring patient compliance with metronidazole usage. Patients who had high proportions of spirochetes, i.e., > 20%, in plaques removed from diseased periodontal sites, were given metronidazole (500 mg bid) under supervision. In all individuals who received the metronidazole, there was a significant and rapid decline and/or disappearance of spirochetes from the plaque during the time interval that metronidazole was detectable in the saliva. This observed decline in spirochetes was then used to determine which patients had been compliant in a double-blind clinical trial involving the unsupervised usage of metronidazole. Only 10 of 18 patients (56%) were considered compliant in their usage of metronidazole. These 10 patients experienced a significantly greater benefit from the metronidazole than did the 8 patients who were considered noncompliant, i.e., a reduction of surgical needs of 8.3 teeth per compliant patient versus 3.6 teeth per non compliant patient. A test for the hydrolysis of the synthetic peptide (BANA) was also able to identify most non-compliant patients. Clinical trials involving the unsupervised usage of systemic medication need to take into account patient non compliance. PMID- 8436639 TI - Muir-Torre syndrome associated with a family history of hyperlipidemia. AB - The Muir-Torre syndrome is a rare disorder characterized by sebaceous neoplasms of the skin and multiple visceral malignancies. The syndrome appears to be a familial, autosomal dominant condition. We diagnosed this syndrome in a previously unreported patient and found a personal and family history of malignancies and hyperlipidemia. The association of Muir-Torre syndrome with a family history of hyperlipidemia, another autosomal dominant condition, has not been previously reported. The possible genetic relationship between the two disorders is discussed. PMID- 8436640 TI - Dermatitis in treated maple syrup urine disease. AB - Two children who had classic maple syrup urine disease developed an eruptive dermatitis when plasma isoleucine levels, leucine levels, or both fell below normal during periods of protein restriction. The dermatitis was resistant to topical corticosteroid therapy. Rapid resolution occurred after treatment with isoleucine and leucine dietary supplements. PMID- 8436641 TI - Extensive cutaneous hyperpigmentation caused by minocycline. AB - A 65-year-old man had cutaneous hyperpigmentation that had occurred over the previous 2 1/2 years. The hyperpigmentation was extensive and involved the sclerae, nail beds, and total body; the palms and buttocks were spared. Clinical diagnosis was suggestive of hemochromatosis or heavy metal deposition. Histologic and electron microscopic findings were consistent with lysosomal iron deposition. A careful history showed that minocycline was the cause. Its use was discontinued, and after several years the patient's pigmentation is gradually returning to normal. PMID- 8436642 TI - Nonfamilial diffuse palmoplantar keratoderma associated with bronchial carcinoma. AB - A 61-year-old black woman had epidermoid carcinoma of the lung and the recent onset of diffuse hyperkeratosis of the palms and soles. These findings suggested an association between internal malignancy and palmoplantar hyperkeratosis. This report discusses the palmoplantar keratodermas, including those associated with malignancy. PMID- 8436643 TI - Painful tumors of the skin: "LEND AN EGG". AB - Some tumors of the skin are difficult to diagnose because they are clinically nondescript. However, if they are painful, nine unique tumors should be considered. In addition to the commonly accepted tender lesions, we describe a painful nodule in a patient who proved to have a granular cell tumor. We summarize the clinical and histologic features of the "LEND AN EGG" tumors: leiomyoma, eccrine spiradenoma, neuroma, dermatofibroma, angiolipoma, neurilemmoma, endometrioma, glomus tumor, and granular cell tumor. PMID- 8436644 TI - Rothmund-Thomson syndrome with osteosarcoma. AB - Rothmund-Thomson syndrome is a rare genodermatosis that features a progressive, early-onset poikiloderma, a high incidence of juvenile cataracts, stunted growth, and a wide range of skeletal abnormalities. We report the seventh case of osteosarcoma in a patient with Rothmund-Thomson syndrome and review the previous reports describing this association. PMID- 8436645 TI - Chronic hyperkeratotic herpes zoster and human immunodeficiency virus infection. AB - A patient with human immunodeficiency virus infection had hyperkeratotic papules in the T 11 and T 12 dermatomes in which she previously had papulovesicular herpes zoster. Findings of a biopsy specimen and viral culture of these papules subsequently revealed varicella-zoster that eventually responded to prolonged high-dose acyclovir therapy and debridement. A review of reported cases of hyperkeratotic varicella-zoster infections is presented, in addition to our recommendations for the treatment of varicella-zoster infection in patients who have acquired immunodeficiency syndrome. PMID- 8436646 TI - Ross syndrome: treatment of segmental compensatory hyperhidrosis by a modified iontophoretic device. AB - In 1958 the triad of tonic pupils, areflexia (Holmes-Adie syndrome), and hypohidrosis was first described by Ross. Since then more than 15 patients with a similar condition have been described. Two cases with the typical triad in combination with associated autonomic dysfunctions are presented. Subjectively, the most disturbing symptom is segmental compensatory hyperhidrosis, which results from widespread hypohidrosis or anhidrosis. For treatment of hyperhidrosis, tap water iontophoresis was applied using a modified technique with special electrodes. In both patients the hyperhidrosis was relieved after 20 treatments. PMID- 8436647 TI - Recurrent erythema migrans despite extended antibiotic treatment with minocycline in a patient with persisting Borrelia burgdorferi infection. AB - Erythema migrans recurred in a patient 6 months after a course of treatment with minocycline for Lyme disease. Polymerase chain reaction on heparinized peripheral blood at that time demonstrated the presence of Borrelia burgdorferi-specific DNA. The patient was seronegative by Lyme enzyme-linked immunosorbent assay but showed suspicious bands on Western blot. Findings of a Warthin-Starry stain of a skin biopsy specimen of the eruption revealed a Borrelia-compatible structure. Reinfection was not believed to have occurred. Further treatment with minocycline led to resolution of the erythema migrans. PMID- 8436648 TI - Granulomatous panniculitis caused by Candida albicans: a case presenting with multiple leg ulcers. AB - A 61-year-old woman had rapidly enlarging ulcers on both legs and three draining subcutaneous nodules on the left thigh. Findings of skin biopsy specimens revealed granulomatous panniculitis with a large number of blastospores and pseudohyphae. Candida albicans was cultured from the ulcers, the nodules, the mouth, the esophagus and gastric juice, feces, and urine. The ulcers healed after 5 months of therapy with itraconazole. Predisposing factors were diabetes mellitus, dysfunction of the hypothalamic-pituitary system, hypochromic anemia, and prior treatment with a broad-spectrum antibiotic. In contrast to three other reported cases of Candida panniculitis, our patient had not undergone immunosuppressive therapy. PMID- 8436649 TI - Identification of Mycobacterium tuberculosis DNA in a case of lupus vulgaris. AB - A variety of cutaneous lesions are believed to result from the presence of Mycobacterium tuberculosis. Demonstration of M. tuberculosis directly or in culture in some of these eruptions can be difficult. We studied a typical case of lupus vulgaris that had been followed for several years with frequent unrewarding biopsies and cultures to see if M. tuberculosis DNA could be demonstrated in skin biopsy specimens. We used the polymerase chain reaction and a primer/probe set specific for a region in the gene for the 65 kd antigen of M. tuberculosis to search for M. tuberculosis complex DNA. M. tuberculosis complex DNA was demonstrated in archival skin biopsy specimens from the lesion of lupus vulgaris. The polymerase chain reaction and specific primer/probe sequences can be used to demonstrate M. tuberculosis complex DNA in skin lesions. A variety of skin lesions believed to be related to tuberculosis (tuberculids) can be revisited with these techniques and studied for the presence of an infectious agent. PMID- 8436650 TI - Occurrence of basal cell carcinoma among multiple trichoepitheliomas. AB - We describe four patients who developed basal cell carcinoma (BCC) among multiple facial trichoepitheliomas. The only clinical feature that distinguished the carcinomas from the trichoepitheliomas was their larger size in three of the four patients. None of the lesions ulcerated. Whether the BCCs developed independently or by transformation from a trichoepithelioma is uncertain. Mohs micrographic surgery was helpful in revealing the transition from one tumor type to the other so that as much normal tissue as possible could be saved. The literature on the relationship between multiple hereditary trichoepitheliomas and BCCs is reviewed. PMID- 8436651 TI - Cutaneous large-cell lymphoma histologically resembling sarcoidosis. AB - A case of cutaneous T-cell lymphoma with histologic characteristics of sarcoidosis is reported. Although the patient responded to chemotherapy, a subsequent relapse and the eventual death of the patient underscores the aggressive nature of this condition. PMID- 8436652 TI - Pemphigoid vegetans represents a bullous pemphigoid variant. Patient's IgG autoantibodies identify the major bullous pemphigoid antigen. AB - Pemphigoid vegetans is a rare disease; only four cases have been reported. The relationship of pemphigoid vegetans to bullous pemphigoid is not completely defined. We describe a case in a 77-year-old woman who had multiple well circumscribed, erythematous, erosive, and vegetating plaques in the axillae and inframammary areas and in the neck. Microscopic examination revealed epidermal hyperplasia, dermoepidermal junctional separation, and prominent dermal eosinophilia. In the perilesional skin IgG was deposited linearly at the basement membrane zone. In addition, our patient's IgG autoantibodies, primarily the IgG4 subclass, reacted with the epidermal side of salt-split normal human skin and with the 230 kd major bullous pemphigoid antigen. We conclude that pemphigoid vegetans is best classified as a bullous pemphigoid variant. PMID- 8436653 TI - Primary lymphocutaneous nocardiosis caused by an unusual species of Nocardia: Nocardia transvalensis. AB - We present the first case of lymphocutaneous nocardiosis caused by Nocardia transvalensis and the seventh report of infection caused by this microorganism. The patient was allergic to sulfonamides but responded to amikacin and cefotaxime and later to erythromycin. The treatment and criteria for differentiation of cutaneous Nocardia species infection are discussed. PMID- 8436654 TI - Cutaneous and subcutaneous phaeohyphomycosis caused by Exserohilum rostratum. AB - Phaeohyphomycosis of the skin caused by Exserohilum is rare. Four cases have been reported; all were subcutaneous in type and all were caused by Exserohilum rostratum. We report two types of skin infection, cutaneous and subcutaneous, that were caused by E. rostratum in two immunocompromised men. Pleomorphic fungal elements were noted within the dermal suppurative and granulomatous infiltrate in case 1 and only within the central hyperkeratotic horny layer of a porokeratosis like lesion in case 2. E. rostratum was isolated in both cases. Case 2 represents the first documented case of cutaneous Exserohilum phaeohyphomycosis. The clinical and histologic features in this case resembled superficial porokeratosis. To the best of our knowledge these findings have not been reported previously in fungal infections of the skin. The ambiguous terminology that is used in the classification of phaeohyphomycosis is also discussed. PMID- 8436655 TI - Cutaneous reactions to vitamin K1 injections. AB - Cutaneous reactions to vitamin K1 injections are reported infrequently. Most previously reported cases have been associated with liver disease, primarily alcoholic cirrhosis and viral hepatitis. Four new cases are reported. One patient had polycythemia vera and the Budd-Chiari syndrome, the second such report in the literature. The other three patients had no known hepatic disease. The reactions consisted of erythematous plaques at the injection site without progression to sclerodermatous plaques. Histopathologic examination in three cases showed spongiotic changes and mononuclear infiltrates typical of cutaneous reactions to vitamin K1. In one instance a neutrophilic infiltrate was associated with the reaction site. Our findings support the observation that liver disease is not a necessary condition for the occurrence of vitamin K1 hypersensitivity. PMID- 8436656 TI - Juvenile dermatomyositis associated with partial lipoatrophy. AB - A 26-year-old woman developed partial lipoatrophy 12 years after juvenile dermatomyositis was diagnosed. Renal function was normal, but she had other features typically associated with partial lipoatrophy, including hepatomegaly, acanthosis nigricans, hypertrichosis, and hyperinsulinemia. PMID- 8436657 TI - Cutaneous nodules of Mycobacterium chelonae in an immunosuppressed patient with preexisting pulmonary colonization. AB - A 30-year-old immunocompromised man with known pulmonary Mycobacterium chelonae colonization developed a systemic infection with cutaneous manifestations. The eruption consisted of multiple, nontender, subcutaneous nodules on the extremities. A diagnosis of disseminated M. chelonae was made on the basis of recovery of M. chelonae subspecies abscessus from blood and bronchoalveolar lavage fluid and histologic evidence of acid-fast bacilli in a skin biopsy specimen. We believe this is the first reported case of disseminated M. chelonae infection in an immunocompromised host in whom a primary source of the infection was identified. PMID- 8436658 TI - A case of cutaneous T-cell lymphoma expressing gamma delta T-cell receptors. AB - Cutaneous T-cell lymphoma expressing gamma delta T-cell receptors (TCRs) is rare; only a few cases have been reported. We report another case of the disease that had a fatal outcome and differs from two previously reported cases in its clinical, histologic, and immunohistochemical aspects. The patient had multiple skin tumors with central crusts; she showed no response to chemotherapy and died within 1 year. Histologic findings included perivascular infiltrates in the dermis and subcutaneous tissue with no epidermotropism; the large lymphoid cells had a phenotype of CD1-, CD3+, CD4-, CD8-, CD25-/+, CD30-, CD38-/+, HLA-DR+, and gamma delta TCR (beta F1-, TCR delta 1+, delta TCS1-, Ti gamma A+, BB3-). The differences in the phenotype of gamma delta T-cell malignancies may reflect the uniqueness of its clinical and histologic features. A study of gamma delta T-cell malignancies may disclose important biologic features of gamma delta TCR+ cells. PMID- 8436659 TI - Necrosis of the hand after extravasation of intravenously administered phenytoin. AB - Extravascular escape of intravenously administered phenytoin can result in serious local soft tissue complications. Injury can range from simple phlebitis to chemical cellulitis or, in extreme cases, frank tissue necrosis that necessitates amputation. The histopathologic findings include extensive necrosis and sloughing of epidermis, widespread necrosis of dermis, subcutaneous tissue, muscles and nerves, and extensive thrombotic occlusion of vessel lumens. Results of elastic tissue stains reveal that the thrombosed vessels are exclusively veins and venules. Vascular fibrinoid necrosis, leukocytoclasis, and true inflammatory vasculitis are not features. This is the first detailed report of the histopathologic alterations associated with this therapeutic misadventure. PMID- 8436660 TI - Variability in the Michelin tire syndrome. A child with multiple anomalies, smooth muscle hamartoma, and familial paracentric inversion of chromosome 7q. AB - We describe a 2 1/2-year-old boy who has hirsutism and ringed creases of the extremities associated with an underlying smooth muscle hamartoma. Cutaneous findings in this child resemble those in other reports of the "Michelin tire syndrome." Histologic examination showed numerous well-demarcated fascicles of smooth muscle cells randomly distributed at all levels of the reticular dermis with haphazard orientation. These cells were immunoreactive with desmin, which confirmed their smooth muscle nature. In addition to the skin changes, this child has multiple unusual phenotypic anomalies, some of which have not previously been associated with the Michelin tire syndrome. These include distinctive facial dysmorphia, submucous cleft palate, lateral clefting of the mouth, genital, and dental anomalies. He also developed seizures at age 2 1/2 years and has moderate developmental delay. The patient and his mother have apparently identical paracentric inversions of the long arm of chromosome 7 (46,XY,inv(7)(q22q31.3) with no detectable loss or gain of either chromosomal material or DNA markers from the cystic fibrosis (CFTR) region. The relevance, if any, of the karyotypic abnormality to the phenotype in this child is discussed. PMID- 8436661 TI - Application of reversed-phase HPLC to the study of proteolysis in UHT milk. PMID- 8436662 TI - Comparative study by HPLC of caseinomacropeptides from cows', ewes' and goats' milk. PMID- 8436663 TI - Effects of oxytocin, machine stripping and milking rate on production loss of cows milked once a day. AB - The effect of treatments designed to improve the efficiency of milk removal and minimize loss of production in cows milked once a day (OAD) was assessed in short term trials involving Friesian and Jersey cows. Trial 1 involved 80 cows and compared twice a day (TAD) milking with OAD milking with the administration of 20 i.u. of oxytocin (OX), OAD milking with udder massage before and during milking (OS) and no treatment during OAD milking (OC). The OX and OS groups had increased yields of milk and milk solids when treatments were applied, though yields were not restored to previous TAD levels. The percentage increase shown by OX cows was greater than that of OS cows for fat yield. The level of residual milk in the udder after milking was lower for the OX group than for the OAD and TAD controls. In Trial 2, 12 cows were subjected to fast or slow rates of milking OAD in each of two periods. Losses in milk, fat and protein yields averaged 9.1, 9.9 and 1.0% respectively. Increased rate of milking reduced milking time and time to let-down but did not affect response to OAD milking. The results showed that treatments that increased the evacuation of the udder during milking and decreased the level of residual milk reduced losses in production that occur on OAD milking. Increasing the rate of milking was ineffective in reducing losses on OAD milking. PMID- 8436664 TI - Classification of newly calved cows into moderate and severe responders to experimentally induced Escherichia coli mastitis. AB - In the present study newly calved cows were tentatively classified as moderate and severe responders to experimentally induced Escherichia coli mastitis based upon the reactive oxygen species (ROS)-generating capacity of their blood neutrophils before infection. The groups differed in blood and milk composition prior to infection. This initial classification was supported by the corresponding variation in clinical symptoms and in the changes in milk production and composition measured during mastitis. Responses of newly calved cows to Esch. coli challenge varied from mild to severe symptoms of inflammation in infected glands and differed in the intensity of systemic disturbances and general illness. Losses in milk yield and compositional changes were most pronounced in inflamed glands and in severe responders. In inflamed glands milk yield and composition did not return to preinfection level in either moderate or severe responders. The yields of lactose, alpha-lactalbumin, casein and fat followed the same pattern as milk yield. It is concluded that the severe and long lasting systemic disturbances observed in severe responders can be ascribed to absorption of endotoxin from infected glands into circulation, indicating the important role of endotoxin in the pathology of coliform mastitis in periparturient cows. Evaluation of the ROS-generating capacity of blood neutrophils and blood and milk composition before infection might help to predict the cow's sensitivity to Esch. coli mastitis. PMID- 8436665 TI - Effect of pre-milking teat dipping on clinical mastitis on dairy farms in England. AB - Two trials were conducted to investigate the effect of pre-milking teat dipping (PMTD) on mastitis caused by environmentally associated pathogens. The first trial showed considerable variation in effect between herds, so a second, larger trial was conducted. In this second trial a comparison of the rate of clinical mastitis was made between nine matched pairs of dairy herds over 24 weeks of the winter housed period. All herds were near the national average incidence of mastitis before the trial. One member of each pair used their normal method of udder preparation throughout the trial and disinfected all teats after milking with an iodophor disinfectant. In the other nine herds the preparation of all teats, at all milkings, included dipping in a 0.25% available iodine disinfectant, which was left on the teat for 30 s. Every teat was then wiped with a paper towel before cluster attachment. There was no difference in the overall rate of mastitis or the incidence of mastitis caused by any particular type or group of pathogens between the trial groups of herds. Both groups showed a reduction in mastitis compared with the previous winter. Although there were apparent benefits in some pairs of herds there was no overall benefit. In comparison with the previous winter the control herds reported a greater reduction in mastitis than the PMTD herds. The effect of trial supervision on normal practice gave a benefit which overwhelmed any effect of PMTD. There appeared to be no effect of PMTD on the total bacterial count, cell count or iodine content of bulk tank milk. There appears to be no justification for wholesale use of PMTD although most farms and risk groups could benefit from better attention to conventional mastitis control. PMID- 8436667 TI - Purification and identification of TGF-beta 2-related growth factor from bovine colostrum. AB - Bovine colostrum contains transforming growth factor (TGF)-beta-like activity. High levels of this activity are found in early colostrum (within 12 h after parturition); however, it decreases rapidly after 30 h. In this study, the activity in early colostrum was purified by a sequence of decaseination, DEAE Sephacel chromatography, Sephadex G-100 gel filtration, precipitation at neutral pH, further gel filtration and reversed-phase FPLC. A homodimeric 23 kDa protein was identified that retained the TGF-beta-like activity. Its activity was completely neutralized by a specific anti-TGF-beta 2 antibody. These results indicate that the TGF-beta-like growth factor found in bovine colostrum is chemically and antigenically related to TGF-beta 2. The physiological roles of the TGF-beta 2-related growth factor are discussed. PMID- 8436666 TI - Comparison of the ability to bind lipids of beta-lactoglobulin and serum albumin of milk from ruminant and non-ruminant species. AB - The interaction of sheep, horse, pig, human and guinea-pig whey proteins with fatty acids has been studied. Using gel filtration and autoradiography, it was found that sheep beta-lactoglobulin and serum albumin from all species had the ability to bind fatty acids in vitro. Sheep beta-lactoglobulin, isolated from milk, had approximately 0.5 mol fatty acids bound per mol monomer protein, and albumin from sheep, horse and pig contained approximately 4.5, 2.9 and 4.7 mol fatty acids/mol protein respectively. However, beta-lactoglobulin from horse and pig milk had neither fatty acids physiologically bound nor the ability to bind them in vitro. Albumin was the only whey protein detected with bound fatty acids in these species as well as in human and guinea pig. This suggests that the ability of ruminant beta-lactoglobulin to bind fatty acids was not shared by the same protein of non-ruminants. PMID- 8436668 TI - Oral administration of calcium salts for treatment of hypocalcemia in cattle. AB - Milk fever is usually treated by i.v. administration of 8 to 10 g of Ca. Oral Ca salts have been suggested as an alternate treatment for milk fever. In our studies, plasma Ca concentration changes effected by various oral Ca preparations were compared. Solutions were administered by oral drenching of cows, and blood was obtained hourly. Calcium chloride increased plasma Ca better than Ca propionate, which increased plasma Ca better than Ca carbonate. A CaCl2 gel formulation increased plasma Ca better than Ca carbonate, but not as well as did Ca propionate. Concentrated solutions of Ca as CaCl2 increased plasma Ca better than diluted solutions. Rumen bypass of Ca salts increased plasma Ca concentration more than when Ca salts were placed into the rumen. Oral administration of 50 g of Ca as CaCl2 raised plasma Ca concentrations to the same extent as 4 g of Ca as CaCl2 given i.v. We also examined effects of oral Ca salts on plasma Ca concentrations of hypocalcemic periparturient cows and found that oral Ca treatment could treat mild cases of hypocalcemia. We also caution that CaCl2 use must be limited because excessive amounts cause severe metabolic acidosis. PMID- 8436669 TI - Therapeutic effects of simultaneous use of glucose and insulin in ketotic dairy cows. AB - A glucose tolerance test was carried out on 8 ketotic dairy cows and 5 healthy dairy cows after injection of 500 ml of 50% glucose solution into the jugular vein. The blood insulin concentration increased from 6.3 microU/ml before glucose injection to 62.5 microU/ml after injection in the healthy group and from 3.0 to 22.9 microU/ml in the ketotic group. Insulin concentration before glucose injection was lower, and its increase after glucose injection was smaller, in the ketotic group. Five hundred milliliters of 50% glucose solution were administered to 15 ketotic cows by intravenous infusion once daily from d 1 to 6, and 200 U of insulin were injected subcutaneously in 8 of these cows from d 2 to 6. In the group administered insulin with glucose, the blood glucose concentration, insulin concentration, and insulin to glucagon ratio (50.5 mg/dl, 6.2 microU/ml, and .09, respectively) on d 6 were significantly higher than those for cows administered glucose only (36.3 mg/dl, 3.0 microU/ml, and .04, respectively). Also, the blood ketone bodies and free fatty acid concentrations on d 6 were significantly lower in the group receiving glucose plus insulin (22.1 microU/ml and .79 meq/L, respectively) than in the group receiving glucose alone (63.8 microU/ml and .98 meq/L, respectively). Thus, the simultaneous use of glucose and insulin is considered to be useful for the treatment of ketosis in dairy cows. PMID- 8436670 TI - Use of the Fossomatic method to determine somatic cell counts in sheep milk. AB - The Fossomatic method for SCC was compared with the direct microscopic method in 85 half-udder samples of sheep milk. The correlation coefficient was .986. The repeatability of the Fossomatic method showed average variation coefficients less than 5%. The carry-over effect between samples was less than 5%. The effect of the storage method (fresh milk, refrigerated at 4 degrees C and frozen at -19 degrees C) and the sample age were studied in 48 samples of foremilk and strippings. The storage method had a significant effect on the SCC variation. The average fresh, refrigerated, and frozen sample counts were 125,000, 110,000, and 82,000 cells/ml for foremilk and 201,000, 192,000, and 145,000 cells/ml for strippings, respectively. The effect of age on the refrigerated samples was also significant; counts were reduced by about 14% from d 1 to 7 in both types of milk. The effect of age on the frozen sample varied. These results suggest standardization of age and storage conditions of the milk samples to reduce variation of SCC. The milk must not be frozen. PMID- 8436671 TI - Chewing activity and digestive responses of cows fed alfalfa forages. AB - Nonlactating Guernsey cows were fed alfalfa silage or coarsely chopped, coarsely chopped and reconstituted, or long alfalfa hays. A computer system was developed to monitor chewing activity. Effects of diets upon chewing activity, digestibility, and ruminal parameters were determined. Digestibilities of DM and N were lower for silage than for hays. Cows fed silage had lower ruminal ammonia concentrations that were caused, at least in part, by greater bound N. Digestibilities of DM, N, and fiber were not different among the hays. The computer system recorded 98% of chews; visual measurements of chewing activity agreed well with computer-logged data. Cows spent more time (463 vs. 348 min/d) eating long alfalfa hay than silage; time spent ruminating, total chewing time, and chewing rates were not different among diets. During eating, cows fed hay had more chews per unit of DM or NDF than when eating silage; during rumination, diets had no effect. Eating time of cows fed alfalfa silage was less than for those fed alfalfa hay. Coarsely chopped alfalfa hay was as effective as long alfalfa hay in eliciting chewing activity. PMID- 8436672 TI - Milk composition, ruminal characteristics, and nutrient utilization in dairy cows fed partially hydrogenated tallow. AB - Four Holstein cows (84 DIM) were used in a 4 x 4 Latin square with 21-d periods to determine the effects of increasing amounts of partially hydrogenated tallow in the diet. Tallow replaced ground shelled corn at 0, 2, 4, or 6% of total DM; diets contained 3.3, 5.1, 7.3, and 9.0% total fatty acids. Feces and urine were collected during d 16 to 21 of each period. Milk production (31.1, 31.7, 34.6, and 32.8 kg/d), milk fat content, and DMI (21.2, 20.8, 22.2, and 21.5 kg/d) were not significantly different among diets supplemented with 0, 2, 4, or 6% tallow. Tallow decreased contents of CP and SNF in milk but increased production of NPN. Percentages of short- and medium-chain fatty acids in milk fat decreased linearly, whereas percentage of C18:1 increased with increasing dietary tallow. Ruminal pH, concentrations of total VFA and NH3 N, molar percentages of VFA, and acetate to propionate ratio did not differ among treatments. Total tract apparent digestibilities of DM, OM, NDF, ADF, cellulose, hemicellulose, ether extract, energy, and soluble residue did not differ among treatments. Digestibility of total fatty acids decreased in diets containing tallow. Increasing tallow linearly increased N apparently absorbed, but utilization of energy and N was not significantly different among treatments. Partially hydrogenated tallow included at 6% or less of dietary DM did not adversely affect DMI, digestibilities, or ruminal fermentation characteristics. PMID- 8436673 TI - Supplemental dietary fat from extruded soybeans and calcium soaps of fatty acids for lactating cows. AB - Holstein cows (n = 33) were assigned to one of three diets containing soybean meal, supplemental fat from extruded soybeans, or supplemental fat from Ca soaps of fatty acids. Total mixed diets containing (DM basis) 25% corn silage, 25% alfalfa hay, and 50% of the respective concentrate mixtures were fed wk 4 through 15 postpartum. Milk production (29.2, 32.4, and 31.8 kg/d) was higher for cows fed supplemental fat diets. Milk protein percentages (2.99, 2.93, and 2.81) were higher for cows fed the soybean meal diet and were higher with extruded soybeans than with Ca soaps of fatty acids. Milk fat percentages (3.20, 2.69, and 3.47) were higher for cows fed Ca soaps of fatty acids than for cows fed extruded soybeans. Milk fat from cows fed supplemental fat was more unsaturated than from those fed soybean meal and was most unsaturated from cows fed extruded soybeans. Dry matter intakes (17.8, 18.4, and 16.6 kg/d) were not significantly different among diets. Extruded soybeans and Ca soaps of fatty acids were equally effective in increasing milk production, but milk fat content was reduced, and the proportion of unsaturated fatty acids in milk fat was increased, with extruded soybeans. PMID- 8436674 TI - Analysis of conductance changes as a growth index of lactic acid bacteria in milk. AB - The analysis of changes in conductance is a valid method to evaluate the growth and metabolic activity of lactic acid bacteria in milk. This technique allows the activity of pure strains to be monitored and the stability of the characteristics of mixed cultures to be controlled. The conductimetric method may be particularly useful for the dairy industry to control the stability of lactic acid bacteria starters. PMID- 8436675 TI - Production and reproduction responses by dairy cows fed varying undegradable protein coated with rumen bypass fat. AB - Calcium soaps of fatty acids were used to coat proteins, thus reducing rumen degradability. This material was used to determine the effects of either increasing undegradable intake protein with constant CP or varying degradable protein with constant undegradable protein intake. Increased undegradable intake protein and Ca soaps fed for 120 DIM enhanced milk fat and FCM production during 140 and 305 DIM. Reproductive performance also was improved. Feed efficiency and partial efficiency of milk production were enhanced. Varying degradable protein intake at constant undegradable protein intake using proteins coated with Ca soap resulted in decreased production when degradable protein intake was .4 kg/d lower than NRC recommendations, but no differences were significant when intakes were close to or .5 kg/d above NRC recommendations. Use of Ca soaps to coat proteins appears to be useful to optimize protein supply to dairy cows while increasing ration energy density. PMID- 8436676 TI - Effect of undegradable protein amount fed prepartum on postpartum production in first lactation Holstein cows. AB - Twenty primigravid Holsteins were paired by expected calving date and estimated producing ability and assigned randomly to one of two diets to determine the effect of prepartum supplemented undegradable protein on subsequent productive performance. Diets were isocaloric, isonitrogenous for degradable protein and differed in undegradable protein content. Prepartum diets were fed for ad libitum intake for 3 wk prior to calving. Following parturition, a single diet was offered for ad libitum intake. Cows did not differ in initial BW or body condition score. Body condition score, BW, and milk composition were measured weekly, starting at calving through the first 6 wk of lactation, Milk production was measured daily. Prepartum diet did not influence calf birth weight or mean prepartum DMI. Prepartum diet containing increased undegradable protein improved body condition score at calving through wk 6 postcalving and increased milk protein percentage. Mean daily protein production was consistently greater for the prepartum diet with additional undegradable protein. Milk, FCM, and milk fat were not influenced by prepartum diet. Supplemental undegradable protein prepartum may improve postpartum performance by minimizing mobilization of maternal labile protein pools to meet fetal and maternal growth requirements in late gestation. PMID- 8436677 TI - Carbohydrate and Aspergillus oryzae effects on intake, digestion, and milk production by dairy cows. AB - Six multiparous, ruminally cannulated Holstein cows (46 DIM, 584 kg of BW) and 6 primiparous Holstein cows (35 DIM, 506 kg of BW) were used in two 6 x 6 Latin squares with 21-d periods to examine the effects of level of non-fiber carbohydrate, source of fibrous carbohydrate, and Aspergillus oryzae fermentation extract on intake, digestion, and milk production. Treatments were 42 and 36% non fiber carbohydrate; shelled corn and soybean meal were replaced partially by beet pulp and dried brewers grains or soy hulls and dried brewers grains in 36% non fiber carbohydrate diets. These three diets then were supplemented with 0 or 3 g/d of A. oryzae. Milk production and composition and DMI were not significantly affected by level or source of carbohydrate, although intake of NDF was significantly higher for 36% non-fiber carbohydrate diets. Total tract apparent digestibilities of ADF and NDF were higher for 36% non-fiber carbohydrate diets. Supplementation with A. oryzae did not significantly affect DMI, milk production, or total tract apparent digestibilities; however, milk fat content was decreased. Partial replacement of corn with fibrous carbohydrate sources, beet pulp and soy hulls, did not adversely affect intake or milk production in early lactation cows fed alfalfa silage-based diets. PMID- 8436678 TI - Preweaning intake and postweaning dietary energy effects on intake and metabolism of calves weaned at 26 days of age. AB - Holstein calves (n = 48) were used to evaluate whether preweaning feeding management affects postweaning DMI and metabolism after abrupt weaning at 26 d of age. Calves were fed only whole milk until d 19 of age. From d 19 to 26, calves were provided one of three isocaloric and isonitrogenous diets: milk at 15% of d 1 BW, milk at 12% of d-1 BW plus a grain-based supplement added to the pail, or milk at 12% of d-1 BW and drenched (force-fed) with the supplement. After weaning, calves were offered a low or high energy (1.7 or 5.8% ether extract) starter. From d 26 to 36, starter intake was similar between calves fed the supplement in the pail and those fed only milk but lower than for calves drenched with supplement. Plasma NEFA increased threefold from d 26 to 27, and calves fed only milk had higher NEFA than drenched calves. From d 26 to 42, plasma VFA of drenched calves were higher than those fed only milk. Except for an increase in plasma NEFA at d 36 and 42, high energy starter did not affect any variable. Preweaning drenching of calves stimulated postweaning adaptation to dry diets. Intake postweaning appears to depend more on physiological adaptation to dry diets than a preweaning feeding management. PMID- 8436679 TI - Prevention of bovine mastitis by a premilking teat disinfectant containing chlorous acid and chlorine dioxide. AB - The objective of this study was to evaluate the efficacy of a premilking teat disinfectant for the prevention of mastitis in dairy cows under natural exposure conditions. Predipping was compared with a negative control using a split udder experimental design. All teats were dipped after milking with the same teat dip. Percentage of quarters newly infected by major mastitis pathogens was 34% lower in quarters with teats predipped and postdipped than in quarters with teats postdipped only. New IMI by Streptococcus uberis and Staphylococcus aureus were significantly lower in quarters with teats predipped and postdipped than in quarters with teats postdipped only. Differences in incidence of clinical mastitis between treatment groups approached significance. Predipping and postdipping were no more effective against Gram-negative bacteria, coagulase negative Staphylococcus species, and Corynebacterium bovis than postdipping only. No chapping or irritation of teats was observed, and no adverse effects were noted using the test product as a premilking and postmilking teat disinfectant. Results of this study suggest that predipping and then postdipping with the test product was a more effective procedure against major mastitis pathogens than postdipping only. PMID- 8436680 TI - Biologically active peptides from milk proteins with emphasis on two examples concerning antithrombotic and immunomodulating activities. AB - The present paper is devoted to the study of short peptides derived from milk proteins with physiological activities. Some of them behaved as opioids, enzyme inhibitors that convert angiotensin I, peptides that enhance calcium absorption, antiaggregating and antithrombotic peptides, and immunomodulating peptides. Some possessed several physiological properties, such as the C-terminal part of bovine alpha s1-casein. A strategic zone, containing immunostimulating and opioid peptides, could be located in cow and human beta-caseins. Few of these peptides or precursor peptides have so far been characterized in vivo in blood or brain after ingestion of milk. If, in the future, some of the active peptides cannot be characterized in vivo, they can all nevertheless be synthesized and used either as food additives or in pharmacology. PMID- 8436681 TI - Influence of milk peptides in determining the functionality of milk proteins: a review. AB - Milk is a rich source of functional ingredients. Unfortunately, milk is also rich in surface-active peptides that modulate the functionality of milk proteins. Fractionation, amino acid analysis and sequencing, and computerized hydropathy calculations showed that these peptides are highly amphipathic. These peptides exert their effects primarily by markedly decreasing surface or interfacial tension and by altering the colloidal properties of proteins. The hydrophobically driven association tendency of proteins, which plays a key role in interfacial stability, is diminished because of the masking of hydrophobic patches by the peptides. Destabilization of emulsions, to an extent, may also be due to desorption of proteins from the interface as a result of the greater surface activity of amphipathic peptides. Experiments are described in which controlled hydrolysis to generate trace amounts of peptides significantly altered the functionality of milk protein powders. Some theoretical bases of the observations are discussed. PMID- 8436682 TI - Recent developments in gastrointestinal absorption and tissue utilization of peptides: a review. AB - Considerable evidence has been accumulated regarding the absorption of dipeptides and tripeptides, yet, even with the growing body of knowledge, the nutritional and metabolic significance of peptide absorption is not fully understood, especially in ruminants. Muscle, mammary gland, liver, kidney, intestinal mucosa, and other tissues either have been shown to have, or are suspected to have, the ability to utilize peptides as a source of AA to meet cellular demands. Investigations suggest that ruminal microbes have the ability to produce substantial amounts of small peptides as a consequence of their hydrolysis of dietary proteins. The extent to which intact peptides may be absorbed into the blood is controversial. Some of the inconsistency in reported observations may be because of limitations of analytical procedures, species differences, or both. Peptide absorption appears to be an important physiological process in ruminants and may constitute the primary source of absorbed AA. The recent observation that the stomach region of the gastrointestinal tract may be an important site of peptide absorption is highly significant. Emerging evidence for the contribution that peptide absorption makes to AA provisioning of ruminants may change some of the currently held views about protein utilization in these unique animals. PMID- 8436683 TI - Low molecular weight branched-chain and n-chain fatty acids in caprine and bovine colostrum. AB - Colostrum from French-Alpine and Anglo-Nubian goats and Holstein cows was collected and analyzed for both total and FFA of 12 and fewer carbon atoms. Short chain VFA were separated from long-chain fatty acids using simultaneous distillation extraction. The n-butyl esters of fatty acids were quantified by gas chromatography, and their identity was confirmed by gas chromatography-mass spectrometry. The concentration of decanoic acid was 33 and 83% less in Holstein colostrum than in colostrum from Alpine and Nubian goats, respectively. Colostrum from Nubian goats had twice as much decanoic acid as colostrum from Alpine goats. The FFA in colostrum that differed between species but not between goat breeds were octanoic and decanoic acids. These respective fatty acids were approximately two and three times greater in colostrum from goats than in colostrum from Holsteins. The quantity of decanoic acid was different between goat breeds and between animal species. The ratio of total fatty acid concentration to free-state concentration for hexanoic acid appeared to be useful for differentiating between Nubian and Alpine goat colostrum as well as between Nubian and Holstein colostrums. PMID- 8436684 TI - Rapid determination of sperm cell concentration in bovine semen by flow cytometry. AB - A flow cytometric technique is described for determining sperm concentration in fresh or extended semen with improved accuracy, precision, repeatability, ease of conduct, and rapidity. The technique is designed to measure the ratio of a known number of fluorescent beads admixed with sperm stained with either acridine orange or propidium iodide. A significant advantage of the technique is the distinct resolution between sperm and other particles (e.g., somatic cells, fat droplets, and bacteria in the semen or extender) that interfere in other counting protocols. Field testing of this protocol over the past 3 yr has demonstrated its superiority over the Coulter counter, hemacytometer, and spectrophotometer for accuracy in counting sperm in extended semen and the accuracy of counting sperm in straws based on preextension spectrophotometric determination of sperm concentration. Sperm chromatin quality can be determined simultaneously with this sperm counting procedure. This approach to counting sperm provides an excellent procedure for quality control of sperm numbers in processed semen. PMID- 8436685 TI - Inhibitory effect of bovine follicular fluid on in vitro maturation of bovine oocytes. AB - To investigate its inhibitory properties, bovine follicular fluid was collected at different stages of the estrous cycle from small, medium, and large follicles. Follicular fluids were incubated with germinal vesicle stage, bovine oocytes aspirated from small follicles. Nuclear maturation was determined at 24 h. Bovine follicular fluid inhibited the spontaneous maturation of bovine oocytes. The inhibition was reversed when follicular fluid was removed from oocyte cultures by 24 h. Follicular fluid varied in its ability to inhibit germinal vesicle breakdown according to follicle size and estrual stage. Follicular fluid from both small and medium follicles at estrus had the greatest ability to prevent germinal vesicle breakdown but became less potent postestrus. Follicular fluid from large follicles at estrus had less ability to inhibit germinal vesicle breakdown than fluid from small and medium follicles. Strong germinal vesicle breakdown inhibiting activity was present in large, probably atretic follicles at late metestrus, early diestrus, and mid diestrus. However, follicular fluid from large follicles had less germinal vesicle breakdown inhibiting activity at proestrus than follicular fluid from large follicles at late metestrus, early diestrus, and mid diestrus. This proestrual activity was similar to that in Graafian follicles at estrus. PMID- 8436686 TI - Depressive reactions to failure in a naturalistic setting: a test of the hopelessness and self-esteem theories of depression. AB - We tested the hopelessness and self-esteem theories of depression and an integration of the two by examining whether a stable, global attributional style (attributional diathesis) and low self-esteem interacted with the outcomes students received on a midterm examination to predict their subsequent depressive reactions over the course of 5 days. Students' immediate depressive reactions (on receipt of grades) were predicted solely by the examination outcome, whereas their enduring depressive reactions during the following 4 days were predicted by the Attributional Diathesis x Low Self-Esteem x Failure interaction. The results also indicated that the three-way interaction predicted enduring depressive reactions through the mediating role of hopelessness. PMID- 8436687 TI - Age-cohort changes in the lifetime occurrence of depression and other mental disorders. AB - Data from three samples of adults (Ns = 571, 472, and 989) and a sample of adolescents (N = 1,710) supported the possibility that the prevalence of major depression has been increasing in recent birth cohorts, a phenomenon labeled the age-cohort effect (ACE). A significant ACE for relapse was also found in 1 of the adult samples. In addition, early onset age in the adults (prior to age 25) tended to be associated with relapse. Adults in recent birth cohorts were also found to show an elevated prevalence of other disorders. We examined the power of 4 variables (current mood state, social desirability response bias, labeling, and time interval between the episode and the diagnostic interview) to produce these results without an actual increase in the rate of mental disorder. With 1 exception (labeling), the variables were significantly associated with reports of past episodes of disorder and with birth cohort. Controlling for their influence, however, did not reduce the ACE. PMID- 8436688 TI - On the automatic nature of phobic fear: conditioned electrodermal responses to masked fear-relevant stimuli. AB - Normal subjects (n = 64) were exposed either to pictures of snakes and spiders or to pictures of flowers and mushrooms in a differential conditioning paradigm in which one of the pictures signaled an electric shock. In a subsequent extinction series, these stimuli were presented backwardly masked by another stimulus for half of the subjects, whereas the other half received non-masked extinction. In support of a hypothesis that suggests that nonconscious information-processing mechanisms are sufficient to activate responses to fear-relevant stimuli, differential skin conductance response to masked conditioning and control stimuli was obvious only for subjects conditioned to fear-relevant stimuli. These results were replicated in a second experiment (n = 32), which also demonstrated that the effect was unaffected by which visual half-field was used for stimulus presentation. PMID- 8436689 TI - Adolescent psychopathology: I. Prevalence and incidence of depression and other DSM-III-R disorders in high school students. AB - Data were collected on the point and lifetime prevalences, 1-year incidence, and comorbidity of depression with other disorders (Diagnostic and Statistical Manual of Mental Disorders [3rd ed., rev.]) in a randomly selected sample (n = 1,710) of high school students at point of entry and at 1-year follow-up (n = 1,508). The Schedule for Affective Disorders and Schizophrenia for School-Age Children was used to collect diagnostic information; 9.6% met criteria for a current disorder, more than 33% had experienced a disorder over their lifetimes, and 31.7% of the latter had experienced a second disorder. High relapse rates were found for all disorders, especially for unipolar depression (18.4%) and substance use (15.0%). Female subjects had significantly higher rates at all age levels for unipolar depression, anxiety disorders, eating disorders, and adjustment disorders; male subjects had higher rates of disruptive behavior disorders. PMID- 8436690 TI - Slowness and the preceding preparatory interval effect in schizophrenia. AB - We measured the reaction times (RTs) of schizophrenic (n = 25), matched normal (n = 69), and bipolar (n = 14) subjects to a tone preceded by a preparatory interval (PI; the time between the warning signal and imperative stimulus) of varying length. RTs increase when the PI for the immediately preceding trial (the PPI) is longer than the PI for the current trial. Several studies have shown that this PPI effect (difference score) is heightened in schizophrenia. We replicated this finding. However, we found that the size of the PPI effect within groups increased with overall slowness and that the least squares regression line relating the PPI effect difference score to overall slowness did not differ between groups, nor did schizophrenic subjects' regression line differ from that of normal subjects. Group differences on the PPI effect were also analyzed by taking residuals for members of all groups from the normal subjects' regression line of the PPI effect difference score on overall slowness. Groups did not differ on these residuals, nor did schizophrenic subjects differ from normal subjects. We conclude that the heightening of the PPI effect in schizophrenia is like that observed in equally slow normal subjects. This finding suggests that the PPI effect does not appear to be a promising marker of a distinctive schizophrenic pathology. PMID- 8436691 TI - Psychophysiological assessment of posttraumatic stress disorder imagery in World War II and Korean combat veterans. AB - We assessed the heart rate, skin conductance, and left lateral frontalis electromyographic responses of World War II (WWII) and Korean War male veterans to recollection of their combat experiences by using a script-driven imagery technique previously validated in Vietnam veterans (Pitman et al., 1990; Pitman, Orr, Forgue, de Jong, & Claiborn, 1987). Medication-free subjects were classified on the basis of criteria from the revised third edition of the Diagnostic and Statistical Manual of Mental Disorders into posttraumatic stress disorder (PTSD; n = 8) and non-PTSD (n = 12) groups, which did not differ in overall combat exposure or severity of personal combat events. PTSD subjects' physiological responses during personal combat imagery were markedly larger than those of non PTSD subjects', even though the self-reported emotional responses of the two groups were comparable. A physiological discriminant function derived from Vietnam veterans (Orr et al., 1990) correctly classified 7 of the 8 PTSD subjects (sensitivity was 88%) and 12 of the 12 non-PTSD subjects (specificity was 100%; p < .001). PMID- 8436692 TI - Limits of operationalization: a critique of Spitzer and Endicott's (1978) proposed operational criteria for mental disorder. AB - Spitzer and Endicott (1978) proposed an operational definition of mental disorder that is a more rigorous version of the brief definitions that appeared in the 3rd and revised 3rd editions of the Diagnostic and Statistical Manual of Mental Disorders. The heart of their proposal is a translation of the concept of dysfunction into operational terms. I argue that their definition fails to capture the concept of dysfunction and is subject to many counterexamples. I use my harmful dysfunction account of disorder (Wakefield, 1992a, 1992b), which interprets dysfunction in evolutionary terms, to explain both the appeal and the problems of Spitzer and Endicott's definition and to provide support for the harmful dysfunction view. I conclude that the failure of Spitzer and Endicott's sophisticated attempt at operationalization indicates that nonoperational definitions that use functional concepts must play a role in formulating valid diagnostic criteria. PMID- 8436693 TI - Confirmatory factor analysis of a multidimensional model of bulimia nervosa. AB - In a recent investigation of the psychopathology of bulimia nervosa by Tobin, Johnson, Steinberg, Staats, and Dennis (1991), a multidimensional model for bulimia nervosa was presented, based on the results of an exploratory factor analysis. In the present investigation, these results and the multidimensional model were tested by means of confirmatory factor analysis with 100 women diagnosed as having bulimia nervosa. The results not only support the multidimensional model with the higher order dimensions Affective and Personality Disorder, Bulimic Behaviors, and Restricting Behaviors, but also demonstrate the importance of body dissatisfaction as a significant, and possibly independent, component of bulimia nervosa. PMID- 8436694 TI - Equivalence of body image disturbances in anorexia and bulimia nervosa. AB - A silhouette method, the Body Image Assessment, was used to measure self evaluation of current and ideal body size in three groups: Ss with with anorexia nervosa (n = 37), Ss with bulimia nervosa (n = 59), and normal control Ss (n = 95). Current and ideal body size measures were contrasted across the three groups using body mass index as a covariate to control for the Ss actual body size. Both eating disorder groups judged current body size to be larger and ideal body size to be thinner relative to control Ss. When actual body size was not statistically controlled, Ss with anorexia nervosa judged current body size to be thinner than did control Ss and Ss with bulimia nervosa. These data illustrate the importance of controlling for actual body size when investigating the self-evaluation of body size. PMID- 8436695 TI - Response styles and the duration of episodes of depressed mood. AB - We examined the relationship between ruminative and distracting styles of responding to depressed mood and the duration of mood. Seventy-nine subjects kept accounts of their moods and responses to their moods for 30 consecutive days. The majority of subjects (83%) showed consistent styles of responding to depressed mood. Regression analyses suggested that the more ruminative responses subjects engaged in, the longer their periods of depressed mood, even after taking into account the initial severity of the mood. In addition, women were more likely than men to have a ruminative response style and on some measures to have more severe and long-lasting periods of depression. PMID- 8436696 TI - Hypnotic analgesia: dissociated experience or dissociated control? AB - High-hypnotizable subjects (n = 18) were superior to low-hypnotizable subjects (n = 18) in the extent of pain reduction produced by hypnotic analgesia and by a stress-inoculation procedure. However, stress inoculation but not hypnotic analgesia impaired performance on a cognitively demanding task that competed with pain reduction for cognitive resources. This outcome implies that hypnotic analgesia occurs with little or no cognitive effort to reduce pain and challenges the social psychological model of hypnosis. The findings are also inconsistent with the notion of dissociated experience, which proposes that pain and the cognitive efforts to reduce it are cut off from consciousness by an amnesialike barrier. However, the results do support the notion of dissociated control, which proposes that suggestions for hypnotic analgesia directly activate pain reduction and thereby avert the need for cognitive strategies to reduce pain. PMID- 8436697 TI - Relation of parental alcoholism to early adolescent substance use: a test of three mediating mechanisms. AB - The current study assessed 3 hypothesized mediating mechanisms underlying the relation between parental alcoholism and adolescent substance use. Using structural equation modeling, we analyzed data obtained from a large community sample of adolescent children of alcoholics and a demographically matched comparison group. Results suggested that parental alcoholism influenced adolescent substance use through stress and negative affect pathways, through decreased parental monitoring, and through increased temperamental emotionality (which was associated with heightened negative affect). Both negative affect and impaired parental monitoring were associated with adolescents' membership in a peer network that supported drug use behavior. The data did not support a link between parental alcoholism and temperamental sociability. PMID- 8436698 TI - Reduced regional brain glucose metabolism assessed by positron emission tomography in electrodermal nonresponder schizophrenics: a pilot study. AB - This pilot study examined whether electrodermal nonresponder and responder subgroups of schizophrenic patients differ in regional brain metabolism assessed by Positron Emission Tomography during a continuous performance test. In comparison to both normal controls (n = 6) and responder schizophrenics (n = 3), the nonresponder schizophrenics (n = 3) showed about a 20% reduction in metabolic rate across the entire brain. Nonresponder schizophrenics tended to have lower absolute metabolic rates than responders in lateral and medial frontal, thalamic, and hippocampal areas. Nonresponders also had significantly lower relative metabolic rates in medial frontal and hippocampal areas as well as the right amygdala. These data suggest that electrodermal subgroups of schizophrenics differ in both regionally specific brain metabolic processes thought to be involved in electrodermal activity and in generalized brain metabolism. PMID- 8436699 TI - Cognitions, depressive symptoms, and development in adolescents. AB - This study examined the generalizability of cognitive models of depression to adolescents and explored developmental differences with regard to depressotypic cognitions. Self-reported depressive symptoms and various hypothesized cognitive correlates (e.g., automatic thoughts, attributions, dysfunctional attitudes) were investigated in a sample of 688 adolescents in grades 7 through 12. Measures of normative adolescent cognitions (e.g., egocentrism, self-consciousness) also were included. There was a strong association between negative thinking and depression in adolescents. There was no association between depressogenic thinking and age, nor did the strength of the association between negative cognitions and depression vary from early to middle adolescence. Finally, negative cognitions were associated with self-report measures of both depressive and anxious symptoms. PMID- 8436700 TI - Dimensions of perfectionism, daily stress, and depression: a test of the specific vulnerability hypothesis. AB - We tested whether perfectionism dimensions interact with specific stressors to predict depression. A depressed patient sample (N = 51) and a general psychiatric sample (N = 94) completed measures of perfectionism, hassles, and depression. Subjects in Sample 2 also completed other personality measures to assess the amount of unique variance in depression. Partial support was obtained in that in both samples self-oriented perfectionism interacted only with achievement stressors to predict depression. Socially prescribed perfectionism interacted with interpersonal stress in Sample 1 and with achievement stress in Sample 2 to predict depression. Several personality variables, including socially prescribed perfectionism, accounted for unique variance in depression. The results suggest that perfectionism dimensions are associated with depression and may constitute specific vulnerability factors. PMID- 8436701 TI - Coping, defending, and the relations between moral judgment and moral behavior in prostitutes and other female juvenile delinquents. AB - Twenty female juvenile delinquents who acknowledged engaging in prostitution, 20 juvenile delinquents who denied doing so, and 20 same-age control subjects responded to Colby and Kohlberg's (1987) Moral Judgment Interview (MJI), a moral dilemma about prostitution, and Joffe and Naditch's (1977) test of coping and defending. Delinquents scored lower on moral maturity and coping and higher on defensiveness than nondelinquents. Post hoc analyses revealed that low-coping delinquents (but not high-coping delinquents or control subjects) made significantly lower level moral judgments on the prostitution dilemma than on the less personally relevant MJI dilemmas. Groups did not differ in their prescriptive judgments on the MJI, but prostitutes made weaker judgments against prostitution than the other delinquents. Prescriptive judgments were not related to moral maturity. The results elucidate the relation between moral judgment and moral behavior. PMID- 8436702 TI - Backward-masking performance in chronic and nonchronic schizophrenics, affectively disturbed patients, and normal control subjects. AB - There is ample evidence that schizophrenics exhibit a backward masking deficit. To what extent other psychotic patients are susceptible to visual masking is still an open question. Likewise, differences between subgroups of schizophrenics have to be further explored. In the present study a computerized backward masking task was applied to 30 schizophrenics, 18 affectives and 20 normals. Results confirmed previous findings of a performance deficit in the schizophrenics. However, affectively disturbed patients performed even poorer than the schizophrenics. The most outstanding finding when the group of schizophrenics was split into different subgroups was the significant differences that appeared between chronic and nonchronic patients. The latter group (n = 8) performed as well as the normals, while the chronic schizophrenics (n = 22) showed evidence of a performance deficit comparable to the affectives. PMID- 8436704 TI - Perception of self and other in major depression. AB - Previous research on the nature of person perception in depression has been inconclusive. This investigation differs from earlier studies in that extensive free-response descriptions of other people and self were collected from patients with major depression and from nonpsychiatric control Ss. In comparison with control Ss, depressed patients described fewer positive aspects not only of self but also of parents and significant others and reported more negative aspects of these people. Cluster analysis (HICLAS) also showed that more cognitive differentiation of negative self-perceptions (negative self-complexity) was characteristic of clinical depression. In both control Ss and patients, a positive (or negative) view of self was highly correlated (.85 or more) with a positive (or negative) view of parents and significant others. These correlations were significantly stronger than those between self and less important others. PMID- 8436703 TI - Emotion in the criminal psychopath: startle reflex modulation. AB - Startle-elicited blinks were measured during presentation of affective slides to test hypotheses concerning emotional responding in psychopaths. Subjects were 54 incarcerated sexual offenders divided into nonpsychopathic, psychopathic, and mixed groups based on file and interview data. Consistent with findings for normal college students, nonpsychopaths and mixed subjects showed a significant linear relationship between slide valence and startle magnitude, with startle responses largest during unpleasant slides and smallest during pleasant slides. This effect was absent in psychopaths. Group differences in startle modulation were related to affective features of psychopathy, but not to antisocial behavior per se. Psychopathy had no effect on autonomic or self-report responses to slides. These results suggest an abnormality in the processing of emotional stimuli by psychopaths that manifests itself independently of affective report. PMID- 8436705 TI - Nursing, technology and the human condition. PMID- 8436706 TI - Pushing techniques in the second stage of labour. AB - It is routine to require women to 'take a deep breath in, hold it and push' in the second stage of labour, but there is no scientific evidence to support this practice. In a randomized controlled trial of spontaneous (n = 15) versus directed (n = 17) pushing in the second stage, no adverse effects of spontaneous pushing on the woman or baby were found. There was a negative correlation between the length of the second stage and the venous cord blood pH at delivery in the directed pushing group, suggesting that a long second stage was disadvantageous to the fetus when the woman was using a directed pushing technique. No such association was found in the spontaneous pushing group, despite the fact that the women in this group had a significantly longer mean second stage. PMID- 8436707 TI - Postpartum depression: women's help-seeking behaviour and perceptions of cause. AB - Research on postnatal depression has largely concentrated on investigating its possible causes. There have been few attempts to examine women's own perceptions and experiences of the condition or to explore the implications which these might have for help seeking and professional intervention. This paper reports on the experiences of depression of a sample of 60 first-time mothers. For the purposes of the study, depression was defined as the experience of depressed mood for a period of at least 2 weeks at some stage during the first 9 months postpartum. On this definition, depression was reported by a high proportion of the mothers (63%) and was found to be of early onset and lengthy duration. The majority of depressed mothers did not seek help from any source and only a quarter of them consulted a health professional. These low rates of consultation are explained in terms of mothers' perceptions of the cause of their depression, their ideas about appropriate solutions and their reluctance to admit to experiencing emotional difficulties. The implications of the study for intervention by health professionals are discussed. PMID- 8436708 TI - Care of sick children by parents: a meaningful role. AB - Parental involvement in their child's care in hospital has undergone great change over the last century. Studies have shown how 'maternal deprivation' and 'separation anxiety' expressed by children are detrimental to a child's recovery in hospital. Striving efforts have been made to develop family-centred care, promote normality of the family unit and continue with the normal routine of the child's life within the limitations of a hospital environment and the child's illness. Expectations of the parental role in hospital need to be identified and expressed from both the parents and staff to establish an understanding that will ultimately be best for the child. Many studies have highlighted benefits to both parent and child from parental participation in hospital. However, disadvantages have been identified from resident parents who feel captive to their new situation and role. Efforts for family-centred care are highly advocated now. Care-by-Parent units have been set up in some areas to promote this idea and, although many advantages have been identified, they are not without their problems. The success of parental involvement is dependent on both parents' and staff's attitudes, enthusiasm and willingness to work together. PMID- 8436709 TI - Caring is loving. AB - This paper explores nursing's current fascination with defining and exploring the term 'caring'. Fear of caring is proposed as the reason for this fascination. Factors at the root of this fear are identified and an expanded definition of caring (one which arises from the dispelling of such fear) is proposed. This expanded definition is given a new label--loving. For, as this author contends, has not loving always been at the heart of nursing? PMID- 8436710 TI - Caregivers' emotional well-being and their capacity to learn about stroke. AB - This study examines the effects of distress on the capacity of informal caregivers of stroke patients to absorb information about stroke and caregiving. Thirty-seven caregivers took part in a stroke seminar. Minor psychiatric symptoms were related to caregivers' knowledge prior to the seminar, with the more emotionally distressed being the least knowledgeable. The emotional state of the caregivers, however, did not affect how much they learnt. Knowledge after the seminar was best predicted from pre-seminar knowledge and age. Older caregivers were less well-informed afterwards, although they did not differ significantly from younger caregivers in their scores initially. These findings do not discount the possibility that emotional carers are too shocked to take in information from hospital staff at the time of admission. The data do demonstrate that, given time to accept the caregiving role, emotional carers are receptive to learning about stroke and the stroke patient's needs. PMID- 8436711 TI - Social support and health: a review. AB - This paper addresses the importance of social support to health, drawing upon relevant literature from medical, psychological and social research. Conceptual and methodological problems are addressed and two major theories ('buffer' and 'attachment') are evaluated for their relevance in explaining the nature, purpose and function of social support. Finally, possible directions for future research in this field are outlined. PMID- 8436712 TI - A conceptual clarification of respect. AB - The concept of respect, while frequently used in nursing literature, has not been extensively defined conceptually or empirically from a nursing perspective. This paper develops a conceptual definition of respect as a phenomenon in the domain of nursing action. Respect emerges as a primary nursing ethic that serves as the basis for our attitudinal, cognitive and behavioural orientation toward people. A comparison of respect to related nursing concepts reveals that respect is a component of and antecedent to caring, presence, confirmation and humanized care. A set of operational definitions of respect is proposed for use in research, education and practice. Potential methods for measuring respect as a nursing action or attitude are discussed. Several applications of respect for nursing are addressed, including the impact of lack of respect on patient-provider interactions, consideration of respect in a cultural context, and identification of client groups for which respect may have particularly significant implications. The paper concludes with recommendations for further research, with emphasis on the meaning and implications of respect for clients. PMID- 8436713 TI - Family work with patients suffering from schizophrenia: the impact of training on psychiatric nurses' attitude and knowledge. AB - The effectiveness of family work with patients suffering from schizophrenia is well established. However, so far working with families has been carried out by highly skilled research workers. It is argued that training should be carried out to disseminate skills so that family work can be carried out routinely in clinical settings. This paper reports the impact of two pilot studies on psychiatric nurses. It was found that the trainees gained in knowledge about schizophrenia and schizophrenia family work. Furthermore, their attitudes and beliefs about schizophrenia and schizophrenia family work changed in the desired direction. The results suggest that it is possible to teach psychiatric nurses an effective model of family work for patients with schizophrenia. PMID- 8436714 TI - Psychophysiological effects of back massage on elderly institutionalized patients. AB - An experimental design was used to measure the effects of back massage on anxiety levels of elderly residents in a long-term care institution. Twenty-one residents, 17 females and four males, participated in the study. Subjects were randomly assigned to three groups which received 'back massage with normal conversation', 'conversation only' and 'no intervention' respectively. The dependent variable, anxiety, was measured prior to back massage, immediately following, and 10 minutes later, on four consecutive evenings. The Spielberger Self-Evaluation Questionnaire (STAI), electromyographic recordings, systolic blood pressure, diastolic blood pressure (DBP) and heart rate were used as measures of anxiety. Analysis of variance was used to examine differences in group mean scores over the pre-test to post-test, post-test to delayed time interval, and pre-test to delayed time intervals, Scheffe comparisons being made where indicated. With the exception of mean DBP which showed no change from pre test to post-test and HR which increased from post-test to delayed time interval, there was a statistically insignificant decrease in mean scores on all variables in the back massage group from pre-test to post-test and from post-test to delayed time interval. There was a statistically significant difference in the mean anxiety (STAI) score between the back massage group and the no intervention group. The difference between the back massage group and the conversation only group approached statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8436715 TI - Client satisfaction, extended intervention and interpersonal skills in community mental health. AB - Some reservations have been expressed about the use of the concept of client satisfaction in relation to clients' views of services received. There has also been little research on clients' perspectives of mental health work. This paper explores client satisfaction with extended intervention from practitioners based at a community mental health centre. Considerable differences are identified between satisfied and not satisfied clients in the service received and their perception. These relate clearly to the use of interpersonal skills such as those of communication, empathy, listening, openness and genuineness. Taken together with research on brief intervention, this paper both indicates that the concept of satisfaction does meaningfully represent the client's experience and provides considerable support for the fundamental importance of the acquisition and use of these skills in practice. PMID- 8436716 TI - Fatigue associated with congestive heart failure: use of Levine's Conservation Model. AB - This study aimed to refine and extend the findings of an original study which focused on the description of fatigue associated with congestive heart failure. A descriptive approach based on Levine's Conservation Model provided both quantitative and qualitative data. Qualitative data addressed personal integrity and quantitative data measured energy conservation, structural and social integrity. Patients described fatigue as being tired and exhausted and containing both physical and emotional components. Fatigue occurred as a result of stress, physical activity and disease. Patient-identified interventions included rest, distraction, medicine, and physical and spiritual activities. Age, pH and oxygen saturation were significantly related to fatigue. The findings are examined using the concept of adaptation as defined by Levine. Implications for nursing are discussed within the framework of the Conservation Model with emphasis on a holistic approach to patient care. PMID- 8436717 TI - Measuring the quality of care in psychogeriatric wards. AB - This paper discusses the way in which quality of care has been measured and in particular draws attention to the vagueness of concepts such as autonomy, individuality and dignity. In our research we have put forward a number of indicators for the quality of care received by patients and, in addition, we have constructed a method by which they can be measured, through the use of standardized observation schedules. This paper therefore describes our indicators and the data collection process followed. This aspect of our work is part of a larger study into work satisfaction and quality of care in psychogeriatric wards in Scotland. Ultimately, the data will allow us to identify factors affecting high and low levels of job satisfaction as well as factors influencing good and bad quality of care. Further, we will be able to examine any association between work satisfaction and the quality of care delivered to patients. The results of this research are due to be published shortly. PMID- 8436718 TI - Ethical decision making on starting terminal care in different health-care units. AB - Set in the context of a major research project on terminal care for cancer patients, this paper examines the process in which the ethical decision is taken to proceed to the stage of terminal care. The sample consisted of 191 nurses from three different health-care units in Finland: a health centre, a central hospital and a radiotherapy clinic. The data were collected in August and September 1989 by means of a postal questionnaire, and they were analysed by cross-tabulation and chi-squared tests. According to the nurses in all three units, there is often no definite and explicit decision to commence terminal care with elderly cancer patients. It was felt that patients and relatives have only very little say in the decision-making process. The nurses themselves would also have wanted to be more closely involved. Most of them said that the decision is usually taken by the doctor alone, especially in the central hospital. The nurses at the radiotherapy clinic said that almost all of their patients are informed of the decision to start terminal care. At the health centre and central hospital, only less than half of the patients are informed. PMID- 8436719 TI - The clinical role of the nurse teacher in the United Kingdom. AB - The focus of this paper is the clinical role of the nurse teacher. Using selected findings from a small exploratory study in which a questionnaire was used to gather quantitative and qualitative data from teachers about their role, three areas are discussed. Examination of the number of clinical areas teachers link with identified three different models of clinical contact. The frequency and timing of teachers' visits to clinical areas are not evenly distributed and some of the reasons for this are discussed. The nature of the clinical role is explored with emphasis on liaison and teachers' perceptions of support of students and clinical staff. Finally, teachers' perceptions of their clinical skill and the implications of this is discussed. It is concluded that all three areas require further analysis if the role of the nurse teacher is to be clarified and made more effective in the future. PMID- 8436720 TI - Reflective peer journals: developing authentic nurses. AB - Nursing education courses often require students to write about their learning experiences in a journal or a log book. Students write the journal/log and submit it to the instructor. The instructor reads, comments, and may or may not grade it. This paper is a reflection on the use and misuse of journals in nursing education from the viewpoints of students and instructors. Related literature is integrated into a dialogue with concepts that relate to nursing education. A theoretical framework, a format and guidelines for peer journals are presented, along with the rationale for having students keep peer journals rather than student/instructor logs. PMID- 8436721 TI - Action research: what is it? How has it been used and how can it be used in nursing? AB - Action research has enjoyed increasing popularity across a wide variety of disciplines including nursing. Action research was designed specifically to bridge the gap between theory, research and practice and incorporates both humanistic and naturalistic scientific methods. As such, action research is a highly compelling method for nursing. However, action research does not easily lend itself to definition. A variety of approaches, definitions and uses have emerged since it was created by Kurt Lewin and have given rise to much debate within social and behavioural sciences. This confusion has carried over into nursing literature without any systematic identification of or debate about the core characteristics of action research or the multitude of approaches or uses that have come to be associated with this method. Thus this paper addresses the central characteristics, three major approaches to action research that exist today and how action research has been used and can be used in nursing. PMID- 8436722 TI - Action research and quality of care: a mechanism for agreeing basic values as a precursor to change. AB - This paper describes the trend apparent in nursing and other practice disciplines towards more participative and collaborative methods of enquiry as exemplified by action research. In so doing it notes the conceptual similarities between action research, change theory and quality initiatives. Particular attention is focused on the need to establish the basic values which provide the impetus and direction for subsequent activity. The difficulties this may pose are illustrated by reference to the application in two continuing care hospital wards for elderly patients of a checklist operationalizing a typology of care. A mechanism to facilitate and make explicit the values underpinning care in any given environment is suggested. PMID- 8436723 TI - How to make the right choice: a new model for the selection interview. AB - The problems encountered when selecting new members of staff in the higher education setting are those universal in any type of organization. Nursing faculties, however, have an even greater difficulty in selecting appropriate staff owing to the diversity of both clinical and academic backgrounds of applicants. The organization is therefore stimulated and challenged in its ability to select the right employee for the job. The literature tends to support the use of group decision making in selection and the function of the group in the interview setting is to evaluate the applicant's prior learning against desirable characteristics. From an analysis of the literature, criteria relating to desirable employee characteristics for nurse academics have been developed. The author has identified a new model to use in assisting the selection panel in predicting the right person for the job. PMID- 8436724 TI - Career guidance during nurse training: findings from an exploratory study. AB - This research into the career guidance experiences of nurses during their training was undertaken as an exploratory study upon which a series of larger studies will subsequently be based. Additionally, it contributed to a national cohort study of the careers of newly qualified registered general nurses. One hundred and twelve nurses were involved in the development and testing of questions for a postal questionnaire to be used in the cohort study of careers. Some problems encountered when investigating career guidance by questionnaire are described, in the light of which a revised research design is proposed and the career guidance experiences of 31 nurses presented. Twenty-one aspects of guidance were investigated, covering information and advice about applying for first post, post-basic courses and longer-term plans. PMID- 8436725 TI - On the integration of science and practice in college health. PMID- 8436726 TI - Adolescent risk behaviors and the potential for violence: a look at what's coming to campus. AB - This study analyzed the types and predictors of violent behaviors reported by students in Grades 11 and 12 in South Carolina. Results are based upon responses of 2,299 students from 57 schools, approximately 3% of the total state enrollment in those grades. The 70-item self-report Youth Risk Behavior Survey developed and piloted by the Federal Centers for Disease Control was used to collect data. The authors performed a series of logistic regression analyses to explore the relation of the demographic and potential risk variables to fighting and carrying weapons. Results from the simple logistic analyses, adjusting for race and gender, indicated that alcohol use, binge drinking, sexual activity, and use of any drugs were significantly associated (p < .05) with reported fighting. These variables and poor academic self-image were significantly associated with carrying weapons. Comprehensive multivariable models indicated that, when considered simultaneously, being black, male, sexually active, and engaging in binge drinking and drug use were significant predictors of fighting. Gender, but not race, alcohol use, drug use, or sexual activity, remained a significant predictor of carrying a weapon. Findings suggest that college risk-reduction and health-promotion programs should direct efforts at environmental modification, policy development and enforcement, as well as at personal change, including effective conflict resolution, stress management, and communication skills. PMID- 8436727 TI - Sexual coercion experience and help-seeking behavior of college women. AB - In a study of 656 college women enrolled in elective health education classes at three midwestern universities, results showed that 42% of the women had been victims of sexual coercion in dating situations while in college. Seventy percent of those who had experienced sexual coercion had intercourse when they did not want to as a result of overwhelming arguments and pressure. Only 28% of the sexual coercion victims sought any type of help. Of those who sought help, 75% sought help from a friend. Because the experience of victimization can disrupt various aspects of women's lives, it is important that victims seek help in their attempts to cope successfully after the sexually coercive event. If campus help providers--administrators, educators, residence hall staff, and health center personnel--are more aware of the incidence and dynamics of sexual coercion, they can be more effective in encouraging college student victims to seek the help they need. PMID- 8436728 TI - Healthy dating: a mixed-gender date rape workshop. AB - College communities are increasingly being called upon to institute date rape prevention programs. This article describes a mixed-gender workshop sponsored by a university's Program for Rape Education and Prevention that was given to more than 1,400 undergraduate students in more than 80 presentations. In order to guide modifications of the workshop, formative evaluation data collected from 330 male (mean age 20.3 years) and 314 female (mean age 20.5 years) university students were collected. Results were largely positive. Despite the sensitive nature of the topic, only 10.2% of the men and 8.2% of the women reported being uncomfortable discussing date rape in mixed-gender groups. Furthermore, students were virtually unanimous in their agreement that date rape is a topic worthy of a workshop. PMID- 8436729 TI - An evaluation of a mixed-gender date rape prevention workshop. AB - A randomized, posttest-only experimental design was used to compare the date-rape attitudes of university students who were exposed to a mixed-gender date-rape workshop (n = 163) with those of students who were not exposed (n = 168). A previously validated instrument, the 25-item Date Rape Attitudes Survey (DRAS), was used as the criterion measure. Three hypotheses were tested, with the following results: (1) Men reported attitudes that were more tolerant of date rape than those reported by women (ie, the men were more likely to condone date rape); (2) students in the control group reported attitudes that were more tolerant of date rape than those reported by students in the treatment group; and (3) men exhibited a greater effect from the program than did women. Finally, the authors discuss implications of the study and offer recommendations for future research evaluating date-rape prevention programs. PMID- 8436730 TI - The experience of violence: a student viewpoint. PMID- 8436731 TI - Seat belt use on a university campus. AB - Observed seat belt use on a private university campus was compared with use by the general population of the state in which the university is located. It was expected, given the higher educational level and socioeconomic status of the university population, that seat belt use would be higher than it is for the general population. The results of the study indicated that seat belt use by members of the university community was actually significantly lower than that reported statewide. The statistically significant difference was even greater for front-seat passengers than for drivers on campus. PMID- 8436732 TI - A dietary procedure for preventing dental caries in young adults. AB - Significant improvement in the dental caries status of children in the United States has been seen in recent decades. The percentage of children who are free from dental caries, however, rapidly decreases with age. By the time young people enter colleges or universities, only a few are caries free. Colleges and universities are places where the young are simultaneously, and perhaps for the last time, reachable as large cohorts before their lives undergo further "individualization." This makes college age a time that is crucial for channeling information about proper oral health practices by organizing mass-directed strategies for prevention of dental caries. It is now clear that dental caries can effectively be prevented. This calls for placing strong emphasis on dietary behavior and on the use of sugar substitutes as part of the strategy. Scientific evidence also suggests that the addition of small daily quantities of xylitol, a natural carbohydrate sweetener, to the diet of children and young adults causes significant reduction in the incidence of dental caries. On the basis of detailed long-term clinical trials carried out during the past 20 years, it appears that a reduction ranging from 30% to more than 85% in dental caries can be achieved simply by using a few xylitol chewing gums daily over a period of 1 to 3 years. In individual cases, virtually total, long-term protection against caries has been observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8436733 TI - Who should get influenza vaccine? PMID- 8436734 TI - Comparison of high energy direct current and radiofrequency catheter ablation of the atrioventricular junction. AB - OBJECTIVES: The goal of the study was to determine short- and long-term success and complications of radiofrequency atrioventricular (AV) junction catheter ablation and to compare these with those of high energy direct current catheter ablation. BACKGROUND: Catheter ablation of the AV junction with radiofrequency or direct current energy is an accepted treatment for drug-refractory supraventricular tachycardias. Few data are available on the long-term success and effects of radiofrequency ablation or its comparison with direct current ablation. METHODS: Fifty-four patients who underwent attempted AV junction ablation with radiofrequency energy were followed up for a mean of 24 +/- 8.4 months. These patients were retrospectively compared with 49 patients who underwent attempted AV junction ablation with direct current energy and were followed up for a mean of 41 +/- 23 months. RESULTS: The early success rate at the time of discharge for radiofrequency ablation was 81.5%, which was not statistically different from that for direct current ablation (85.7%). Fewer sessions were required to achieve complete AV block in the radiofrequency group (1.05 +/- 0.23) (mean +/- SD) compared with the direct current group (1.21 +/- 0.41) (p = 0.02). Although overall complication rates were similar for both groups (9.3% in the radiofrequency group and 8.2% in the direct current group), there was a trend toward more life-threatening early complications in those patients who received direct-current shocks (6.8%) than in those who underwent radiofrequency ablation alone (2.3%) (p = 0.1). Early sudden death (one patient), early ventricular tachycardia (two patients) and cardiac tamponade (one patient) were seen only in those patients who underwent ablation with direct current energy, whereas pulmonary embolism (one patient) was the only early life threatening complication in the radiofrequency group. During follow-up, the rate of recurrence of AV conduction was the same (5%) for both the direct current and radiofrequency groups. In the direct current group, one patient died suddenly 2 weeks after the procedure and another had a cardiac arrest due to ventricular tachycardia 6 h after the procedure. In the radiofrequency group, two patients died suddenly at 11 and 7 months, respectively. Two patients, one who had unsuccessful radiofrequency ablation and required direct current ablation, were resuscitated from ventricular tachycardia. CONCLUSIONS: Radiofrequency energy appears to be as efficacious as and perhaps safer than direct current energy for AV junction ablation. PMID- 8436735 TI - Direct current and radiofrequency catheter ablation: so far and yet so near. PMID- 8436736 TI - Safety, feasibility and cost of outpatient radiofrequency catheter ablation of accessory atrioventricular connections. AB - OBJECTIVES: The purpose of this study was to evaluate prospectively the safety, feasibility and cost of performing radiofrequency catheter ablation of accessory atrioventricular (AV) connections on an outpatient basis in 137 cases. BACKGROUND: The efficacy and low complication rate of radiofrequency ablation as performed in the hospital suggested that it might be feasible to perform it on an outpatient basis. METHODS: In 100 cases (73%) performed between September 1, 1991 and April 20, 1992, patients met criteria for treatment as outpatients. Reasons for exclusion were age < 13 or > 70 years (4), anteroseptal location of the accessory AV connection (5 patients), obesity (> 30% of ideal body weight) (4 patients) or clinical indication for hospitalization (24 patients). Patients with only venous punctures had a recovery period of 3 h and those with arterial punctures had a recovery period of 6 h. There were 63 men and 32 women (5 patients underwent two ablation procedures > 1 month apart), with a mean age +/- SD of 36 +/- 13 years. The pathway was left-sided in 67 cases and right-sided or posteroseptal in 33. RESULTS: The procedure was successful in 97 of 100 cases, with a mean procedure duration of 99 +/- 42 min. In 70 cases the patient was discharged the day of ablation, and in 30 cases the patient required a short (< or = 18-h) overnight stay because the procedure was completed too late in the day for recovery in the outpatient facility. The mean duration of observation was 4.8 +/- 1.5 h for outpatients and 15 +/- 1.4 h for patients who underwent overnight hospitalization. At follow-up study, two patients had a clinically significant complication; both had a femoral artery pseudoaneurysm detected > or = 1 week after the procedure and both required surgical repair. Thirty consecutive patients (22 outpatients and 8 hospitalized overnight) undergoing catheter ablation after January 1, 1992 were chosen for a cost analysis. The mean cost of the procedure was $10,183 +/- $1,082. CONCLUSIONS: The majority of patients undergoing radiofrequency catheter ablation of an accessory AV connection can be treated safely on an outpatient basis. PMID- 8436737 TI - Catheter ablation of accessory atrioventricular pathways in young patients: use of long vascular sheaths, the transseptal approach and a retrograde left posterior parallel approach. AB - OBJECTIVES: This study retrospectively assesses the technical aspects of the catheter techniques used to ablate 83 accessory atrioventricular (AV) pathways during 88 procedures in 71 pediatric and adult patients (median age 14 years, range 1 month to 55 years). A number of catheter approaches and techniques evolved that may have improved success and shortened procedure times. BACKGROUND: Radiofrequency catheter ablation of accessory AV pathways can be highly successful. However, the technical difficulty of many of the procedures is masked by the success rate. METHODS: Left free wall, right free wall and septal accessory pathways were ablated with a variety of approaches. RESULTS: Left free wall pathways were ablated successfully by using a standard retrograde approach through the aortic valve in only 10 (24%) of 43 cases. The remaining 33 (76%) required an approach that was either retrograde through the mitral valve (2 of 33), transseptal (21 of 33) or retrograde where the catheter was advanced behind the posterior mitral leaflet at the point of mitral-aortic continuity, so that the catheter course was parallel rather than perpendicular to the mitral anulus (10 of 33). Nineteen of 20 septal pathways were ablated successfully by using either the parallel approach (2 of 29), a transseptal approach (2 of 19), ablation within the coronary sinus or one of its veins (8 of 19) or ablation on the atrial side of the tricuspid valve (7 of 19). Fifteen of 20 right free wall pathways were ablated successfully with a variety of approaches on both the atrial and the ventricular side of the tricuspid valve. Long vascular sheaths were judged to contribute directly to success in 33 (43%) of 77 pathways. The overall success rate has been 93% (77 of 83 pathways), with 100% success for left free wall (43 of 43), 75% for right free wall (15 of 20) and 95% for septal pathways (19 of 20). CONCLUSIONS: Thus, successful ablation of accessory AV pathways in a mixed group of pediatric and adult patients appears to benefit from a wide range of vascular and catheter approaches. PMID- 8436738 TI - Ischemia-induced regional wall motion abnormality is improved after coronary angioplasty: demonstration by dobutamine stress echocardiography. AB - OBJECTIVES: The purpose of this study was to examine whether dobutamine stress echocardiography can detect reversal of ischemia-induced left ventricular regional wall motion abnormality immediately after percutaneous transluminal coronary angioplasty. BACKGROUND: Although angioplasty is routinely performed as a means of coronary revascularization, at present there is a question whether this results in an immediate improvement in ischemia-induced left ventricular regional function. METHODS: Thirty-five patients underwent dobutamine stress echocardiography 24 h before and 24 to 48 h after angiographically successful coronary angioplasty. Only patients with normal wall motion at rest were included. Dobutamine infusion was begun at 5 micrograms/kg per min and increased at 5-min intervals (10, 20, 30, 40 micrograms/kg per min). Echocardiographic images were stored into cine loops and analyzed off line with simultaneous comparison of images acquired at baseline, 5 micrograms/kg per min, peak infusion and recovery. Echocardiographic images were interpreted independently, without knowledge of other data, by two experienced cardiologists using the 16-myocardial segment model. RESULTS: Before angioplasty, dobutamine stress echocardiography induced wall motion abnormalities in 31 patients (88%). Wall motion score at peak dobutamine infusion improved in 28 (90%) of the 31 patients after angioplasty. Wall motion score at peak dobutamine infusion for the group improved from 20 +/- 3 before angioplasty to 17 +/- 2 after angioplasty (p < 0.001). There was no change in the rate-pressure product achieved for the group before and after angioplasty (20,038 +/- 6,415 beats/min x mm Hg before versus 20,775 +/- 5,435 after angioplasty, p = NS). Before angioplasty, dobutamine stress echocardiography induced angina in 13 patients (37%), whereas angina occurred only once after angioplasty. Electrocardiographic changes diagnostic of ischemia occurred seven times, all before angioplasty. CONCLUSIONS: We conclude that dobutamine stress echocardiography is an excellent method to demonstrate an immediate improvement in stress-induced regional left ventricular dysfunction in the distribution of the vessel undergoing successful angioplasty. PMID- 8436739 TI - Prophylactic versus standby cardiopulmonary support for high risk percutaneous transluminal coronary angioplasty. AB - OBJECTIVES: Data from a national registry of 23 centers using cardiopulmonary support (CPS) were analyzed to compare the risks and benefits of prophylactic CPS versus standby CPS for patients undergoing high risk coronary angioplasty. BACKGROUND: Early data from the CPS registry documented a high angioplasty success rate as well as a high procedural morbidity rate. Because of this increased morbidity some high risk patients were placed on standby CPS instead of prophylactic CPS. METHODS: Patients in the prophylactic CPS group had 18F or 20F venous and arterial cannulas inserted and cardiopulmonary bypass initiated. Patients in the standby CPS group were prepared for institution of cardiopulmonary bypass, but bypass was not actually initiated unless the patient sustained irreversible hemodynamic compromise. RESULTS: There were 389 patients in the prophylactic CPS group and 180 in the standby CPS group. The groups were comparable with respect to most baseline characteristics, except that left ventricular ejection fraction was lower in the prophylactic CPS group. Thirteen of the 180 patients in the standby CPS group sustained irreversible hemodynamic compromise during the angioplasty procedure. Emergency institution of CPS was successfully initiated in 12 of these 13 patients in < 5 min. Procedural success was 88.7% for the prophylactic and 84.4% for the standby CPS group (p = NS). Major complications did not differ between groups. However, 42% of patients in the prophylactic CPS group sustained femoral access site complications or required blood transfusions, compared with only 11.7% of patients in the standby CPS group (p < 0.01). Among patients with an ejection fraction < or = 20%, procedural morbidity remained significantly higher in the prophylactic CPS group (41% vs. 9.4%, p < 0.01), but procedural mortality was higher in the standby group (4.8% vs. 18.8%, p < 0.05). CONCLUSIONS: Patients in the standby and prophylactic CPS groups had comparable success and major complication rates, but procedural morbidity was higher in the prophylactic group. When required, standby CPS established immediate hemodynamic support during most angioplasty complications. For most patients, standby CPS was preferable to prophylactic CPS during high risk coronary angioplasty. However, patients with extremely depressed left ventricular function (ejection fraction < 20%) may benefit from institution of prophylactic CPS. PMID- 8436741 TI - Histologic studies in percutaneous transluminal coronary angioplasty for chronic total occlusion: comparison of tapering and abrupt types of occlusion and short and long occluded segments. AB - OBJECTIVES: The purpose of this study was to examine the histologic-angiographic correlates of chronic total coronary occlusion and to explain why a tapering type of occlusion and short occluded segments are favorable for percutaneous transluminal coronary angioplasty. BACKGROUND: Coronary angioplasty is less successful for vessels with chronic total occlusion than for highly stenotic but patent vessels. Several clinical and angiographic factors determining the rate of initial success have been investigated, but the underlying histologic features are not clear. METHODS: Ten autopsy hearts that showed chronic total coronary occlusion on cineangiography performed < or = 3 months before death were selected. In all, the estimated duration of occlusion was > 1 year. At autopsy, postmortem angiography was performed and hearts were fixed with 10% buffered formalin. Occluded segments were sectioned transversely and serially into slices 10 microns thick. Every five slices were stained in hematoxylin-eosin and elastic van-Gieson. RESULTS: Ten hearts with chronic total coronary occlusion were angiographically classified into five with a tapering and five with an abrupt type of occlusion and seven with a short (< or = 15 mm) and three with a long (> 15 mm) occluded segment. Histologically, the occluded segment was composed of loose or dense fibrous tissue, atheroma, small vascular channels and calcified tissue. Reconstruction of the serial preparations showed that small lumen recanalized areas (diameter 160 to 230 microns) with surrounding loose fibrous tissue penetrated the occluded segment in four hearts with occlusion of the tapering type and a short occluded segment. In these four cases, the lack of anterograde flow on cineangiography could be explained by the presence of rich collateral flow. In three cases of the abrupt type of occlusion with a short occluded segment, a mass of loose fibrous tissue penetrated the occluded segment. In hearts with a long occluded segment (one with a tapering type of occlusion and two with an abrupt type), there was no recanalization and loose fibrous tissue was dispersed in the occluded segment. CONCLUSIONS: Chronic total coronary occlusion of the tapering type or with a short occluded segment, or both, is possibly favorable for angioplasty, because small lumen recanalized areas or loose fibrous tissue penetrates the occluded segment and may form a route for successful angioplasty. PMID- 8436740 TI - Lack of impact of early catheterization and fibrin specificity on bleeding complications after thrombolytic therapy. The TAMI Study Group. AB - OBJECTIVES: The aim of this study was to assess the hemorrhagic risk associated with fibrin-specific thrombolytic therapy and invasive procedures with acute myocardial infarction. BACKGROUND: Successful coronary artery reperfusion has important prognostic implications. Because immediate coronary angiography is the only method proved to differentiate early fibrinolytic success from failure, its use may be important for selected patients. METHODS: Five hundred seventy-five patients were evaluated with six combined thrombolytic and catheterization strategies. Patients were randomized to intravenous urokinase alone, recombinant tissue-type plasminogen activator (rt-PA) alone, or both; simultaneously they were randomized to an immediate versus a deferred catheterization strategy. Hemorrhagic events were assessed. The correlation of hemorrhage with clinical and hemostatic variables was evaluated. Prespecified transfusion criteria were employed. RESULTS: No difference in baseline characteristics or in hemorrhagic complications was noted among the three thrombolytic regimens. Although mild (< 250 ml) bleeding was more common in the group with immediate catheterization, no clinically significant difference among catheterization groups was seen in moderate to life-threatening hemorrhagic events. Most bleeding occurred at vascular access sites, yet severe and life-threatening hemorrhage occurred in < 1% of patients. Baseline and nadir fibrinogen levels, change in baseline fibrinogen levels and peak fibrin and fibrinogen degradation products did not correlate with bleeding risk. A clinical predisposition for bleeding was observed in women as well as older (> or = 65 years) and lighter (< or = 70 kg) patients. With prespecified transfusion criteria, only a minimal increase in blood product usage was noted with immediate catheterization. CONCLUSIONS: Immediate cardiac catheterization can be accomplished without a clinically significant difference in bleeding risk. Fibrin specificity offers no clear advantage in reducing hemorrhagic risk. Bleeding risk correlates best with baseline patient characteristics. Finally, the amount of blood transfused can be reduced with lower transfusion criteria. PMID- 8436742 TI - Delayed recovery of coronary resistive vessel function after coronary angioplasty. AB - OBJECTIVES: The aim of this study was to use Doppler catheterization and sequential dynamic positron emission tomography (PET) to investigate the role and time course of abnormal coronary resistive vessel function in the impairment of the coronary vasodilator response (maximal/basal coronary blood flow) after successful coronary angioplasty. BACKGROUND: The coronary vasodilator response may be impaired immediately after coronary angioplasty, despite successful dilation of a flow-limiting stenosis. METHODS: Twelve men (mean age 52 +/- 10 years) with single-vessel coronary artery disease and normal left ventricular function were studied. The coronary vasodilator response to intravenous dipyridamole (0.5 mg.kg-1 over 4 min) was determined from intracoronary Doppler measurement of coronary flow velocity, before and after successful angioplasty. Basal and maximal myocardial blood flow in the angioplasty region and a normal region were determined in nine patients wtih positron emission tomography with H2(15)0 at 1 day (PET1), 7 days (PET2) and 3 months (PET3) after angioplasty. RESULTS: The coronary vasodilator response, measured by Doppler catheterization, was similar before and immediately after angioplasty, 1.63 +/- 0.41 and 1.62 +/- 0.55, respectively (p = NS). After angioplasty, in seven of nine patients without restenosis, basal myocardial blood flow at PET1, PET2 and PET3 was 0.98 +/- 0.16, 0.94 +/- 0.09 and 0.99 +/- 0.13 ml.min-1 x g-1, respectively, in the remote region and 1.19 +/- 0.23 (p < 0.01 vs. remote region), 1.17 +/- 0.19 (p < 0.01 vs. remote region) and 1.10 +/- 0.08 ml.min-1 x g-1 (p = NS vs. remote region), respectively, in the angioplasty region. Myocardial blood flow after dipyridamole at PET1, PET2 and PET3 was 3.04 +/- 0.68, 3.00 +/- 0.71 and 3.00 +/- 0.60 ml.min 1 x g-1, respectively, in the remote region and 2.11 +/- 0.80 (p < 0.01 vs. remote region), 2.28 +/- 0.73 (p = NS vs. remote region) and 3.06 +/- 0.86 ml.min 1 x g-1 (p = NS vs. remote region), respectively, in the angioplasty region. The coronary vasodilator response at PET1, PET2 and PET3 was 3.15 +/- 0.85, 3.18 +/- 0.68 and 3.08 +/- 0.75, respectively, in the remote region and 1.80 +/- 0.68 (p < 0.01 vs. remote region), 1.94 +/- 0.49 (p < 0.01 vs. remote region) and 2.77 +/- 0.74 (p = NS vs. remote region), respectively, in the angioplasty region. CONCLUSIONS: After successful angioplasty, basal myocardial blood flow is increased for > or = 7 days in the angioplasty region, with a reduction in the dipyridamole-induced increase in maximal myocardial blood flow for > or = 24 h after the procedure. Thus, the coronary vasodilator response is impaired for > or = 7 days after angioplasty, indicating that there is abnormal resistive vessel function in the coronary vascular bed distal to a coronary artery stenosis that persists for 7 days to 3 months. PMID- 8436743 TI - Thrombosis of a flexible coil coronary stent: frequency, predictors and clinical outcome. AB - OBJECTIVES: The aim of this study was to evaluate the predictors and clinical sequelae of stent thrombosis. BACKGROUND: Although coronary artery stenting is being increasingly applied, the major unique complication of stent thrombosis is not well characterized. METHODS: We studied 145 patients who underwent coronary artery stenting with the Gianturco-Roubin flexible coil design for abrupt vessel closure or to prevent restenosis. There were 17 stented vessel closures (11.7%), 7 as a result of acute (< 24 h) and 10 of subacute (days 1 to 21) thrombosis. RESULTS: In seven patients successful coronary recanalization was achieved with thrombolytic agents and balloon angioplasty. Creatine kinase was significantly elevated in 13 patients, with a Q wave myocardial infarction in 11 and emergency coronary artery bypass grafting in 8. Comparisons (multivariate analysis) with a control cohort (n = 33) of patients without thrombosis matched for age, gender and vessel stented revealed lesion eccentricity (p = 0.003), unstable angina (p = 0.048) and indication for stent implantation (abrupt closure versus restenosis) (p = 0.002), as predictors of thrombotic occlusion of stented vessels. Subtherapeutic anticoagulation (activated partial thromboplastin time < 2 times control value, prothrombin time < 1.4 control value) occurred at least once during the hospital stay in all 10 patients with subacute thrombosis and in 20 of 33 control patients (p = 0.047). In 2 patients with subacute thrombosis and 11 control subjects, subtherapeutic anticoagulation was necessitated by bleeding. CONCLUSIONS: Early thrombosis after coronary stenting was relatively common (> 10%), occurring predominantly in eccentric lesions and in patients with unstable angina pectoris. This complication is associated with significant adverse clinical outcomes and may be reduced by more intensive anticoagulation yet, in a delicate balance, can be precipitated by inadequate heparin therapy. PMID- 8436744 TI - Clinical and prognostic significance of serum magnesium concentration in patients with severe chronic congestive heart failure: the PROMISE Study. AB - OBJECTIVES: The aim of this study was to determine the prognostic significance of alterations in serum magnesium in patients with moderate to severe congestive heart failure. BACKGROUND: Reductions in serum magnesium have been postulated to play a role in promoting arrhythmias and to have an adverse impact on survival in congestive heart failure, although support for this postulate is lacking. METHODS: Serum magnesium levels were measured in 1,068 patients enrolled in a survival study of class III or IV heart failure at the time of double-blind randomization to milrinone, a phosphodiesterase inhibitor, or placebo. All patients received conventional therapy with digoxin, diuretic drugs and a converting enzyme inhibitor throughout the trial. The median follow-up period was 6.1 months (range 1 day to 20 months). RESULTS: Patients with high serum magnesium (defined as > or = 1.9 mEq/liter, n = 242) were less likely to survive than were patients with a normal magnesium level (n = 627) (p < 0.05, risk ratio = 1.41). Patients with a low magnesium level (defined as < or = 1.5 mEq/liter, n = 199) had no difference in survival compared with the group with a normal magnesium level (p = NS, risk ratio = 0.89). At baseline, the patients in the high magnesium group were older and had more severe functional and renal impairment. An analysis after adjustment for these variables demonstrated no difference in survival comparing the low, normal and high magnesium groups. Although the three groups had no difference in frequency of ventricular tachycardia, length of longest run or frequency of ventricular premature beats on baseline Holter monitoring, the group with hypomagnesemia had more frequent ventricular couplets. CONCLUSIONS: Serum magnesium does not appear to be an independent risk factor for either sudden death or death due to all causes in patients with moderate to severe heart failure. Hypomagnesemia is associated with an increase in the frequency of certain forms of ventricular ectopic activity, but this is not associated with an increase in clinical events. The higher mortality rate among the patients with hypermagnesemia is attributable to older age, more advanced heart failure and renal insufficiency. PMID- 8436745 TI - Pulmonary and peripheral vascular factors are important determinants of peak exercise oxygen uptake in patients with heart failure. AB - OBJECTIVES: This study was conducted to determine the relations among exercise capacity and pulmonary, peripheral vascular, cardiac and neurohormonal factors in patients with chronic heart failure. BACKGROUND: The mechanisms of exercise intolerance in heart failure have not been fully clarified. Previous studies have indicated that peripheral factors such as regional blood flow may be more closely associated with exercise capacity than cardiac function, whereas the role of pulmonary function has received less attention. METHODS: Fifty patients with stable heart failure underwent a comprehensive assessment that included a symptom limited maximal cardiopulmonary exercise test, right heart catheterization, pulmonary function tests, neurohormonal levels, radionuclide ventriculography and forearm blood flow at rest and after 5 min of brachial artery occlusion. Univariate and stepwise linear regression analyses were used to relate peak exercise oxygen uptake to indexes of cardiac, peripheral vascular, pulmonary and neurohormonal factors both alone and in combination. RESULTS: The mean ejection fraction was 19% and peak oxygen uptake was 16.5 ml/min per kg in this group of patients. By univariate analysis, there were no significant correlations between peak oxygen uptake and rest cardiac output, pulmonary wedge pressure, ejection fraction and pulmonary or systemic vascular resistance. In contrast, even in the absence of arterial desaturation during exercise, the forced expiratory volume in 1 s (r = 0.55, p < 0.001), forced vital capacity (r = 0.46, p < 0.01) and diffusing capacity for carbon monoxide (r = 0.47, p < 0.01) were all significantly associated with peak oxygen uptake. Peak postocclusion forearm blood flow (r = 0.45, p < 0.01), the corresponding minimal forearm vascular resistance (r = -0.56; p < 0.01) and plasma norepinephrine level at rest (r = 0.45; p < 0.01) were also significantly correlated with peak oxygen uptake. By multivariate analysis, minimal forearm vascular resistance and forced expiratory volume in 1 s were shown to be independently related to peak oxygen uptake, with a combined R value of 0.71. Other two-variate models included forced expiratory volume and plasma norepinephrine (R = 0.67) and forced expiratory volume and diffusing capacity (R = 0.65). Because forced vital capacity was highly correlated with forced expiratory volume in 1 s, it could be combined with the same variables to yield similar R values. Addition of any third variable did not improve these correlations. CONCLUSIONS: In comparison with rest indexes of cardiac performance, measures of pulmonary function and peripheral vasodilator capacity were more closely associated with peak exercise oxygen uptake in patients with heart failure. Furthermore, the associations were independent of each other and together accounted for 50% of the variance in peak oxygen uptake. These data suggest that pulmonary and peripheral vascular adaptations may be important determinants of exercise intolerance in heart failure. PMID- 8436746 TI - Discordance in degree of right and left ventricular dilation in patients with dilated cardiomyopathy: recognition and clinical implications. AB - OBJECTIVES: The purpose of the present study was to assess the influence of variations in the relative degree of dilation of left and right ventricular chambers on the clinical outcome of patients with dilated cardiomyopathy. BACKGROUND: Dilated cardiomyopathy, a primary myocardial disease characterized by ventricular dilation and systolic dysfunction, is generally associated with a poor prognosis. However, considerable variability has been observed in the clinical course and the morphologic and hemodynamic features in individual patients. METHODS: We evaluated 67 consecutive patients with dilated cardiomyopathy and without evidence of ischemic or primary valvular heart disease. On the basis of diastolic ventricular chamber area measurements obtained by echocardiography, patients were classified into two groups: 38 patients with a relatively equal degree of left and right ventricular dilation (LV congruent to RV) and 29 patients with predominant and disproportionate dilation of the left ventricle (LV > RV). RESULTS: The 67 patients ranged in age from 19 to 81 years (mean 56); 49 (73%) were male. The two subsets of patients with dilated cardiomyopathy did not differ with regard to age, left ventricular diastolic dimension, wall thickness and mass or ejection fraction. However, patients in the LV congruent to RV group showed more severe mitral and tricuspid regurgitation by Doppler echocardiography than did those in the LV > RV group (p = 0.01 for mitral and 0.004 for tricuspid regurgitation). Over the follow-up period of 2 to 60 months (mean 28), there were 19 deaths. Survival in the LV > RV group was significantly better than in the LV congruent to RV group (p = 0.03). CONCLUSIONS: Patients with dilated cardiomyopathy represent a heterogeneous group with regard to both clinical outcome and the relative degree of left and right ventricular chamber dilation. Patients in the LV > RV subset appear to have better overall survival and less severe mitral and tricuspid regurgitation than do patients in the LV congruent to RV subset. Longitudinal studies are needed to determine whether these morphologic subsets in fact represent a continuum within the disease spectrum of dilated cardiomyopathy. PMID- 8436747 TI - Sustained augmentation of parasympathetic tone with angiotensin-converting enzyme inhibition in patients with congestive heart failure. AB - OBJECTIVES: The objective of this investigation was to evaluate the changes in parasympathetic tone associated with long-term angiotensin-converting enzyme inhibitor therapy in patients with congestive heart failure. BACKGROUND: Angiotensin-converting enzyme inhibitors provide hemodynamic and symptomatic benefit and are associated with improved survival in patients with congestive heart failure. Angiotensin II, whose production is ultimately inhibited by these agents, exerts significant regulatory influence on a variety of target organs including the central and peripheral nervous systems. Accordingly, it would be anticipated that angiotensin-converting enzyme inhibitors would significantly alter the autonomic imbalance characteristic of patients with congestive heart failure and that this influence over neural mechanisms of cardiovascular control may significantly contribute to the hemodynamic benefit and improved survival associated with angiotensin-converting enzyme inhibitor therapy. METHODS: In the current investigation, changes in autonomic tone associated with long-term administration of an angiotensin-converting enzyme inhibitor were measured using spectral analysis of heart rate variability in 13 patients with congestive heart failure who were enrolled in a double-blind randomized placebo-controlled trial of the angiotensin-converting enzyme inhibitor zofenopril. Both placebo and treatment groups were balanced at baseline study in terms of functional class, ventricular performance and autonomic tone. RESULTS: After 12 weeks of therapy with placebo, there was no change in total heart rate variability, parasympathetically governed high frequency heart rate variability or sympathetically influenced low frequency heart rate variability. In contrast, therapy with zofenopril was associated with a 50% increase in total heart rate variability (p = 0.09) and a significant (p = 0.03) twofold increase in high frequency heart rate variability, indicating a significant augmentation of parasympathetic tone. CONCLUSIONS: These results demonstrate that long-term treatment of patients having congestive heart failure with an angiotensin converting enzyme inhibitor is associated with a restoration of autonomic balance, which derives in part from a sustained augmentation of parasympathetic tone. Such augmentation of vagal tone is known to be protective against malignant ventricular arrhythmias in patients with ischemic heart disease and therefore may have similar benefit in the setting of ventricular failure, thus contributing to the improved survival associated with angiotensin-converting enzyme inhibitor therapy in patients with congestive heart failure. PMID- 8436748 TI - Importance of left ventricular minimal pressure as a determinant of transmitral flow velocity pattern in the presence of left ventricular systolic dysfunction. AB - OBJECTIVES: This study was designed to assess whether the transmitral flow velocity pattern provides an estimation of left atrial pressure irrespective of the presence of left ventricular systolic dysfunction and, if not, to clarify the mechanism. BACKGROUND: The pulsed Doppler transmitral flow velocity pattern, particularly peak early diastolic filling velocity, has been shown to change in parallel with left atrial pressure. However, extremely elevated left atrial pressure in association with heart failure does not necessarily cause an increase in peak early diastolic filling velocity in patients. METHODS: Left atrial pressure was elevated with intravenous saline infusion in 11 dogs (normal left ventricular function group) and hemodynamic, transesophageal Doppler echocardiographic and M-mode echocardiographic variables were recorded at three different loading levels. In another 12 dogs, left atrial pressure was elevated by production of left ventricular systolic dysfunction with the stepwise injection of microspheres into the left coronary artery (left ventricular dysfunction group) and the same set of recordings was obtained at three different levels of dysfunction. RESULTS: Peak early diastolic filling velocity increased with left atrial pressure in the normal left ventricular function group and correlated with mean left atrial pressure (r = 0.61, p < 0.01) and early diastolic left atrial to left ventricular crossover pressure (r = 0.71, p < 0.01). In contrast, peak early diastolic filling velocity did not increase with left atrial pressure in the left ventricular dysfunction group and did not correlate with mean left atrial pressure (r = -0.05) or the crossover pressure (r = 0.06). Peak early diastolic filling velocity correlated well with the difference between the crossover pressure and left ventricular minimal pressure in the left ventricular dysfunction group (r = 0.64, p < 0.01). In contrast to peak early diastolic filling velocity, deceleration time of the early diastolic filling wave correlated with mean left atrial pressure and the crossover pressure irrespective of the primary cause of preload alteration (r = -0.54, r = -0.59, p < 0.01 respectively, n = 69 for all data). CONCLUSIONS: Preload dependency of the Doppler transmitral flow velocity pattern is hampered if an increase in left atrial pressure is due to left ventricular systolic dysfunction. In this setting, the increase in left ventricular minimal pressure due to left ventricular systolic dysfunction cancels the effect of the increase in left atrial pressure on the flow velocity pattern. PMID- 8436749 TI - Nonparallel changes in global left ventricular chamber volume and muscle mass during the first year after transmural myocardial infarction in humans. AB - OBJECTIVES: This study was designed to serially assess time-dependent changes in both chamber volume and myocardial muscle mass after infarction in humans. BACKGROUND: Dilation of the left ventricular chamber has been previously described after transmural myocardial infarction. METHODS: Global left ventricular chamber volumes and muscle mass were quantified by using cine computed tomographic scanning in 18 patients at hospital discharge and 6 weeks, 6 months and 1 year after an initial transmural myocardial infarction (12 anterior and 6 inferior). No patient had heart failure during the initial hospital stay or on any subsequent follow-up visit. RESULTS: The patients with anterior myocardial infarction (estimated infarct extent 27 +/- 2% of left ventricle) demonstrated a progressive increase in left ventricular end-diastolic volume from 148 +/- 9 ml (mean +/- SEM) at hospital discharge to 180 +/- 9 ml at 1 year after infarction (p < 0.001). However, global left ventricular muscle mass decreased significantly during the 1st 6 weeks after infarction but returned by 1 year to nearly the value determined at hospital discharge (177 +/- 13 vs. 165 +/- 10 g, p = NS). The changes in global muscle mass did not parallel the steady and progressive increases in chamber end-diastolic volume. The end-diastolic chamber volume to muscle mass ratio, an index of global left ventricular wall tension, increased steadily after hospital discharge but remained level by 1 year after infarction. The time course of changes in global end-systolic chamber volume was roughly proportional to the concomitant changes in end-diastolic volume. During this same time period, left ventricular stroke volume remained constant or improved from that determined at baseline. Global left ventricular end-diastolic and end systolic volumes remained relatively static during the 1st year in the patient subgroup with inferior wall myocardial infarction (estimated infarct extent 10 +/ 1% of left ventricle), but global muscle (myocardial) mass initially decreased and then increased in a pattern similar, although of smaller magnitude, to that observed in patients with anterior wall myocardial infarction. CONCLUSIONS: Overall, left ventricular end-diastolic and end-systolic chamber volumes increase progressively from hospital discharge to 1 year after an initial transmural myocardial infarction in patients with a moderately large anterior wall infarction but remain stable in patients with a small inferior wall infarction. Concurrently, total left ventricular muscle mass decreases significantly during the initial 6 weeks after infarction (presumed largely secondary to changes in the necrotic segments) but then returns to the hospital discharge baseline values by 1 year. These data are consistent with the late development of, at most, limited ventricular hypertrophy in the noninfarcted myocardium that occurs well after the early and progressive left ventricular chamber dilation observed in patients with a moderate to large myocardial infarction. These data, in particular as applied to patients with anterior infarction, suggest that ventricular wall tension is significantly elevated at least during the 1st year after an initial transmural myocardial infarction. These observations may explain the potential utility of agents aimed at reducing afterload or ventricular wall tension during the early convalescent phase after myocardial infarction. PMID- 8436750 TI - Benefit of late coronary reperfusion on ventricular morphology and function after myocardial infarction. AB - OBJECTIVES: This study was designed to examine the relation between the timing and adequacy of perfusion of the infarct bed and changes in ventricular size and the extent of abnormal wall motion after acute myocardial infarction. METHODS: A validated echocardiographic mapping technique was used to measure the left ventricular endocardial surface area index and the extent of abnormal wall motion over a 3-month period in 91 patients who had either 1) no anterograde or collateral flow to the infarct bed (n = 14), 2) only collateral flow to the infarct bed (n = 18), 3) restoration of anterograde flow to the infarct bed within hours of chest pain (early [n = 43]), or 4) restoration of anterograde flow to the infarct bed within a mean of 5 days after acute myocardial infarction (late [n = 16]). RESULTS: Over the follow-up period, a progressive and significant increase in endocardial surface area index was observed only in the group of patients without anterograde or collateral flow to the infarct bed (entry 64 +/- 3.4 cm2/m2 vs. 3 months 75.9 +/- 6.4 cm2/m2, p < 0.005). In contrast, a progressive reduction in the extent of abnormal wall motion was evident in the group of patients in whom anterograde flow to the infarct bed was restored within hours (entry 26.7 +/- 2.5 cm2 vs. 3 months 11.8 +/- 2.9 cm2, p < 0.001) or days (entry 22.1 +/- 3.6 cm2 vs. 3 months 11.8 +/- 3.3 cm2, p < 0.001) of coronary occlusion. Multiple stepwise linear regression analysis confirmed that by 3 months, 1) ventricular size was independently related to endocardial surface area index and abnormal wall motion at entry (p < 0.0001) and to the change in abnormal wall motion over the follow-up period (p < 0.0001), and 2) the change in abnormal wall motion was related to the presence of anterograde flow to the infarct bed (p < 0.0001) independent of the timing of reperfusion, infarct site or the extent of abnormal wall motion on admission. CONCLUSIONS: After myocardial infarction, the process of ventricular remodeling is influenced by changes in the extent of abnormal wall motion, which in turn are related to the adequacy rather than the timing of perfusion of the infarct bed. PMID- 8436751 TI - Intracoronary artery thrombus formation in unstable angina: a clinical, biochemical and angiographic correlation. AB - OBJECTIVES: We examined the relation between the level of urinary fibrinopeptide A and the presence of angiographic intracoronary thrombus in patients with unstable angina to determine whether this marker predicts active thrombus formation. BACKGROUND: Although it is known that thrombus plays a role in acute ischemic syndromes, a noninvasive method to predict its presence in individual patients with unstable angina has not been determined. Fibrinopeptide A is a polypeptide cleaved from fibrinogen by thrombin and thus is a sensitive marker of thrombin activity and fibrin generation. METHODS: Angiographic thrombus, graded 0 to 4, and the presence of ST segment depression or T wave inversions, or both, on the electrocardiogram (ECG) were related to fibrinopeptide A levels in 24 patients with rest angina of new onset, 18 with crescendo angina, 19 with stable angina and 9 with chest pain but without coronary artery disease. All patients had chest pain within the 24 h of sample acquisition. RESULTS: The angiographic incidence of thrombus was significantly higher in patients with new onset of rest angina (67%, p < 0.001) and crescendo angina (50%, p < 0.001) as were fibrinopeptide A levels (p = 0.002). Fibrinopeptide A levels correlated significantly (p < 0.001) with the presence of a filling defect (grade 4 intracoronary thrombus) or contrast staining (grade 3). All patients with fibrinopeptide A > or = 8 ng/mg creatinine showed grade 3 to 4 thrombus and 15 of 16 patients with levels > or = 6.0 ng/mg creatinine exhibited angiographic evidence of thrombus (13 with grades 3 to 4). Patients with reversible ST changes on the ECG had significantly higher levels of fibrinopeptide A (p < 0.001), and ST changes correlated significantly with the presence of angiographic thrombus (p < 0.001). Nonetheless, a significant minority of patients with unstable angina had neither angiographic nor biochemical evidence of thrombus. CONCLUSIONS: Elevated fibrinopeptide A levels in unstable angina reflected active intracoronary thrombus formation and were present in patients with angina of new onset as well as crescendo angina. Reversible ST changes are accompanied by thrombin activity and angiographic thrombus formation. However, a sizable percentage of patients with unstable angina had no evidence of thrombus and these patients may have had transient platelet aggregation without fibrin thrombus formation. PMID- 8436752 TI - Prognostic implications of myocardial ischemia during daily life in low risk patients with coronary artery disease. AB - OBJECTIVES: The purpose of this study was to determine the incidence and prognostic importance of myocardial ischemia detected by ambulatory monitoring in low risk, medically managed patients with coronary artery disease. BACKGROUND: Previous studies have demonstrated that certain high risk subsets of patients with coronary artery disease have improved survival with revascularization. The remaining low risk medically managed patients may still have episodes of silent ischemia during daily living, but the frequency and prognostic implications of such episodes in this group are unknown. METHODS: We prospectively studied the incidence and prognostic significance of ST segment changes recorded during daily activities in 116 asymptomatic or mildly symptomatic low risk patients with native coronary artery disease who were followed up for 29 +/- 13 months. Low risk patients were selected after excluding patients with 1) left main disease; 2) three-vessel coronary artery disease and left ventricular dysfunction at rest; 3) three-vessel disease and inducible ischemia during exercise; and 4) two-vessel disease, left ventricular dysfunction and inducible ischemia. RESULTS: Forty-five patients (39%) had transient episodes of ST segment depression during 48-h electrocardiographic (ECG) monitoring (total 217 episodes, lasting 7,223 min, 82% of episodes silent). There were eight acute cardiac events (seven myocardial infarctions, one episode of unstable angina) and nine patients underwent elective revascularization. Seven of the eight acute events occurred in patients without silent ischemia during monitoring. Kaplan-Meier survival analysis revealed no significant differences in event-free survival from either acute or total events in subgroups with or without silent ischemia during ambulatory ECG monitoring. None of the clinical, treadmill exercise, radionuclide ventriculographic or cardiac catheterization variables were predictive of outcome by Cox multivariate proportional hazard function analysis. Analysis of coronary arteriograms before and after acute cardiac events revealed that in five of the six patients studied, acute occlusion occurred in a coronary artery different from the artery with the severest stenosis on initial angiography. CONCLUSIONS: In patients categorized as at low risk on the basis of the results of cardiac catheterization and stress testing, silent myocardial ischemia during daily life was not uncommon, and its presence failed to predict future coronary events. PMID- 8436753 TI - Hemodynamic tolerability and anti-ischemic efficacy of high dose intravenous diltiazem in patients with normal versus impaired ventricular function. AB - OBJECTIVES: This study was designed to compare the acute systemic and coronary hemodynamic effects of high doses of intravenous diltiazem in patients with normal versus impaired left ventricular function, investigate the safety of this drug and compare its anti-ischemic potential in these two patient groups during pacing-induced stress. BACKGROUND: Because coronary hemodynamic effects and negative inotropic properties of diltiazem are dose related, high dose intravenous diltiazem may improve anti-ischemic efficacy but may not be tolerated in patients with impaired cardiac function. METHODS: High dose intravenous diltiazem, 0.4 mg/kg for 5 min followed by 0.4 mg/kg for 10 min, was administered to 23 normotensive patients with coronary artery disease, 11 (group A) with normal and 12 (group B) with impaired ventricular function (ejection fraction < 45%) during two identical arterial pacing stress tests performed 30 min before (pacing test I) and immediately after diltiazem (pacing test II). RESULTS: Diltiazem was well tolerated despite high peak plasma levels, 869 +/- 152 micrograms/liter (group A) and 926 +/- 169 micrograms/liter (group B). It resulted in immediate but similar reductions in systemic resistance from 1,321 +/ 136 (control value) to 963 +/- 113 dynes.s.cm-5 (group A) and from 1,267 +/- 106 to 865 +/- 58 dynes.s.cm-5 (group B) and in mean arterial pressure from 107 +/- 3 to 93 +/- 4 mm Hg (group A) and from 103 +/- 4 to 86 +/- 4 mm Hg (group B), at 5 min after diltiazem (all p < 0.05 vs. control value). Diltiazem improved stroke output from 36 +/- 3 (control value) to 46 +/- 4 ml/beat per m2 in group B and from 44 +/- 4 (control value) to 49 +/- 5 ml/beat per m2 in group A, an effect that was significantly greater and more prolonged in group B than in group A. Although neither heart rate nor contractility was affected in either group, left ventricular end-diastolic pressure increased in group A (9 +/- 2 mm Hg to 12 +/- 1 mm Hg, p < 0.05) but not in group B. Despite similar reductions in coronary resistance and improvements in coronary flow, diltiazem consistently reduced myocardial oxygen extraction, but only in group B. Also, the anti-ischemic effects of diltiazem were more pronounced in group B. During pacing test II, myocardial lactate extraction normalized in group B (7 +/- 5% vs. -6 +/- 12% [pacing test I]) but not in group A, contractility indexes improved more and the increase in left ventricular filling pressure was reduced to a greater extent in group B. Moreover, the ischemia-induced increase in arterial pressures, observed in both groups during pacing test I, was prevented in group B but recurred in group A during pacing test II. CONCLUSIONS: High dose intravenous diltiazem is well tolerated, augments coronary flow and improves left ventricular pump function, particularly in patients with preexisting ventricular dysfunction. As its anti-ischemic effects also appear more pronounced in the latter group, high dose diltiazem may be particularly useful when ventricular function is depressed, for example, during prolonged ischemia at rest. PMID- 8436754 TI - Response of the interatrial septum to transatrial pressure gradients and its potential for predicting pulmonary capillary wedge pressure: an intraoperative study using transesophageal echocardiography in patients during mechanical ventilation. AB - OBJECTIVES: We hypothesized that the directional movement of the interatrial septum and its curvature may reflect the pressure relations between the left and right atria. BACKGROUND: Interventricular septal shape is primarily dependent on the pressure gradient between the left and the right ventricle. No analogous study has carefully evaluated the determinants of interatrial septum shape and motion. METHODS: Patients (n = 52) undergoing cardiac or vascular surgery were studied intraoperatively at multiple intervals with transesophageal echocardiography and simultaneous measurement of central venous pressure, pulmonary capillary wedge pressure and airway pressure. RESULTS: Overall interatrial septum shape, which usually curved toward the right atrium, changed concordantly with the interatrial pressure gradient (pulmonary capillary wedge pressure-central venous pressure difference). The degree of interatrial septum curvature was also primarily dependent on the interatrial pressure gradient and, to a lesser extent, was affected by changes in left atrial size (F = 130.4 vs. F = 14.1). During passive mechanical expiration, the interatrial pressure gradient, usually positive, often reverses transiently and the interatrial septum momentarily bows toward the left atrium. Midsystolic reversal was seen in 64 of 72 episodes when the pulmonary capillary wedge pressure was < or = 15 mm Hg but in only 2 of 40 episodes when it was > 15 mm Hg (sensitivity = 0.89, specificity = 0.95, positive predictive value = 0.97). CONCLUSIONS: These findings suggest that overall interatrial septum shape depends on the pressure gradient between the left and right atria. Midsystolic reversal of the interatrial septum, which probably reflects the increased venous return in the right relative to the left atrium during mechanical expiration, may be a useful indicator of the pulmonary capillary wedge pressure. PMID- 8436755 TI - Frequency domain measures of heart period variability to assess risk late after myocardial infarction. AB - OBJECTIVES: To determine whether spectral measures of heart period (RR) variability predict death when measured late after infarction, we studied patients in the Cardiac Arrhythmia Pilot Study (CAPS) who survived for 1 year and had a 24-h electrocardiographic (ECG) recording made after the CAPS drug was washed out. BACKGROUND: Four components of the heart period power spectrum--ultra low frequency (< 0.0033 Hz), very low frequency (0.0033 to < 0.04 Hz), low frequency (0.04 to < 0.15 Hz) and high frequency power (0.15 to < 0.40 Hz)--plus total power (1.157 x 10(-5) to < 0.40 Hz) and the ratio of low to high frequency power predict mortality when measured < 30 days after myocardial infarction. However, these variables increase to steady state values by 3 months after infarction and the prognostic significance of recovery values is unknown. METHODS: The 24-h power spectral density was computed from ECG recordings made 1 year after infarction using fast Fourier transforms and the six measures listed were calculated. The values were dichotomized at cut points that maximized the association with mortality. RESULTS: Each measure of RR variability had a strong and significant univariate association with mortality; the relative risks for these variables ranged from 2.5 to 5.6. After adjustment for age, New York Heart Association functional class, rales in the coronary care unit, left ventricular ejection fraction and ventricular arrhythmias, some measures of heart period variability still had a strong and significant independent association with all cause mortality. CONCLUSIONS: Spectral measures of heart period variability, measured late after infarction, predict death. PMID- 8436756 TI - Enhancement of Doppler flow signals in the left heart chambers by intravenous injection of sonicated albumin. AB - OBJECTIVES: The objective of this study was to evaluate the effect of a transpulmonary contrast agent on Doppler flow signals in the left heart chambers. BACKGROUND: Echo contrast agents are good ultrasound reflectors and could be used as Doppler signal enhancers. Sonicated albumin microbubbles are transpulmonary echo contrast agents and could enhance left heart Doppler signals after peripheral venous injection. METHODS: Thirty-one patients with various heart diseases without intracardiac shunts were assessed with Doppler echocardiography before and after injection of sonicated albumin. RESULTS: After an intravenous injection, pulsed Doppler signals of transmitral flow became more intense in all 16 patients examined, although flow velocity itself was not changed. In Doppler color flow imaging, the maximal mitral regurgitant signal area increased from 312 +/- 405 mm2 to 434 +/- 465 mm2, an average increase of 59 +/- 40% in all 17 patients with mitral regurgitation (p < 0.01). These effects were considered to be due to improvement of signal to noise ratio by the enhancement of Doppler flow signals. The duration of enhancement of pulsed Doppler transmitral flow signals was significantly longer than that of the left ventricular echocardiographic opacification (44 +/- 11 s vs. 17 +/- 7 s, p < 0.01). CONCLUSIONS: Intravenous injection of sonicated albumin can enhance the Doppler flow signals in the left heart chambers. This effect may be useful to improve the sensitivity of the Doppler system for detecting abnormalities of left heart blood flow such as mitral regurgitation. PMID- 8436757 TI - A new integrated system for three-dimensional echocardiographic reconstruction: development and validation for ventricular volume with application in human subjects. AB - OBJECTIVES: The purpose of this study was to improve three-dimensional echocardiographic reconstruction by developing an automated mechanism for integrating spark gap locating data with corresponding images in real time and to validate use of this mechanism for the measurement of left ventricular volume. BACKGROUND: Initial approaches to three-dimensional echocardiographic reconstruction were often limited by inefficient reconstructive processes requiring manual coordination of two-dimensional images and corresponding spatial locating data. METHODS: In this system, a single computer overlays the binary encoded positional data on the two-dimensional echocardiographic image, which is then recorded on videotape. The same system allows images to be digitized, traced, analyzed and displayed in three dimensions. This system was validated by using it to reconstruct 11 ventricular phantoms (19 to 271 ml) and 11 gel-filled excised ventricles (21 to 236 ml) imaged in intersecting long- and short-axis views and by apical rotation. To measure cavity volume, a surface was generated by an algorithm that takes advantage of the full three-dimensional data set. RESULTS: Reconstructed cavity volumes agreed well with actual values: y = 0.96x + 2.2 for the ventricular phantoms in long- and short-axis views (r = 0.99, SEE = 2.7 ml); y = 0.95x + 2.9 for the phantoms, reconstructed by apical rotation (r = 0.99, SEE = 2.7 ml); and y = 0.99x + 0.11 ml for the excised ventricles (reconstructed in long- and short-axis views; r = 0.99, SEE = 5.9 ml). The mean difference between three-dimensional and actual volumes was 3% of the mean (3.0 ml) for the phantoms and 6% (4.6 ml) for the excised ventricles. Observer variability was 2.3% for the phantoms and 5.6% for the excised ventricles. Application to 14 normal subjects demonstrated feasibility of left ventricular reconstruction, which provided values for stroke volume that agreed well with an independent Doppler measure (y = 0.97x + 0.94; r = 0.95, SEE = 3.2 ml), with an observer variability of 4.9% (2.4 ml). CONCLUSIONS: A system has therefore been developed that automatically integrates locating and imaging data in no more time than the component two-dimensional echocardiographic scans. This system can accurately reconstruct ventricular volumes in vitro over a wide range and is feasible in vivo, thus laying the foundation for further applications. It has increased the efficiency of three-dimensional reconstruction and enhanced our ability to address clinical and research questions with this technique. PMID- 8436758 TI - Clinical significance and origin of artifacts in transesophageal echocardiography of the thoracic aorta. AB - OBJECTIVES: The aim of this study was to identify the mechanism and features of artifacts encountered during transesophageal echocardiography of the aorta. BACKGROUND: Artifacts are an important potential limitation of transesophageal echocardiography of the aorta. METHODS: The mechanism of the artifacts was examined by in vitro modeling. The frequency and clinical correlates of artifacts were examined by retrospective review of transesophageal echocardiograms in 36 patients with aortic pathologic lesions. RESULTS: Two classes of artifact were seen: linear artifacts in the ascending aorta, which may mimic intimal flaps, and mirror image artifacts in the transverse and descending thoracic aorta. Linear artifacts in the ascending aorta, seen in 44% of patients, were shown in vitro to be multiple path artifacts caused by reflection of ultrasound within the left atrium. Linear artifacts in the ascending aorta were associated with dilatation of the ascending aorta and were more frequent when the aortic diameter exceeded the left atrial diameter (p < 0.001). The mirror image artifacts of the transverse and descending thoracic aorta give the appearance of a double-barrel aorta and were shown in vitro to be caused by the aorta-lung interface, which acts as a total reflector of ultrasound. Mirror image artifacts were seen in > 80% of patients. Artifacts were equally frequent with the sagittal and transverse imaging planes when biplane transesophageal echocardiography was used. CONCLUSIONS: Artifacts occur frequently during transesophageal echocardiography of the aorta. An understanding of why they occur and the features that distinguish them from true abnormalities should enhance the diagnostic accuracy of transesophageal echocardiography for aortic disease. PMID- 8436759 TI - Measurements of cardiac output by impedance cardiography in pacemaker patients at rest: effects of various atrioventricular delays. AB - OBJECTIVES: The purpose of this study was to evaluate the ability of impedance cardiography to determine the change in cardiac output caused by modifications in the atrioventricular (AV) delay in DDD (dual-chamber) pacing mode while pacing the atrium and ventricle at different programmed rates. BACKGROUND: Impedance cardiography permits continuous noninvasive monitoring of hemodynamic variables on a beat to beat basis. METHODS: Eleven patients with a DDD pacemaker were evaluated by impedance cardiography. Stroke volume, cardiac output and total peripheral resistance were assessed in the supine rest position during both DDD and ventricular (VVI) pacing. Hemodynamic variables were measured during DDD pacing at rates ranging from 60 to 110 beats/min in 10-beats/min increments with programmed AV delay varying from 50 to 250 ms in 50-ms increments. When the pacemaker was reprogrammed to the VVI pacing mode, these measurements were repeated at the same pacing rates. RESULTS: Cardiac output measurements during programmed conditions were found to be highly reproducible. The mean coefficient of variation was 3% during DDD pacing; it was 6% in the VVI pacing mode. A large decrease in cardiac output (approximately 30%) was found when a pacemaker was reprogrammed from the DDD to the VVI pacing mode. At DDD pacing rates between 70 to 110 beats/min, the highest cardiac output occurred at an average AV delay of < 120 ms from atrial stimulus to ventricular stimulus. At an average AV delay of > or = 200 ms, the cardiac output in the DDD and VVI pacing modes was similar. CONCLUSIONS: 1) Impedance cardiography allows highly reproducible noninvasive assessments of cardiac output in pacemaker patients; 2) inappropriate programming of the AV interval in patients with atrial and ventricular pacing can decrease cardiac output significantly, and the extent of the decrease is similar to or less than that observed in ventricular pacing; 3) hemodynamic measurements obtained with impedance cardiography can facilitate optimal programming of pacemaker variables. PMID- 8436760 TI - Tetralogy of Fallot, truncus arteriosus, abnormal myocardial architecture and anomalies of the aortic arch system induced by bis-diamine in rat fetuses. AB - OBJECTIVES: The aim of this study was to analyze the relation between anomalies of the heart and aortic arch arteries in near-term rat fetuses exposed to the chemical bis-diamine. BACKGROUND: Bis-diamine is known to induce cardiovascular anomalies. METHODS: Bis-diamine was given orally to normal pregnant rats, and the 65 fetuses were examined under a dissecting microscope after formalin fixation. RESULTS: There were 26 rat fetuses (40%) with a ventricular septal defect in the perimembranous portion, of which 14 (22%) had tetralogy of Fallot, 4 (6%) had truncus arteriosus and 8 (12%) had a relatively small defect with no other major anomalies. In 44 fetuses (68%) the middle latitudinal muscle bundle of the ventricular septum was continuous with the right ventricular free wall. There were, isolated or in association, a double- or right aortic arch in 6 fetuses (9%), aberrant subclavian arteries in 9 (14%), right ductus arteriosus in 12 (18%) and agenetic ductus in 4 (6%). The cross-sectional area of the ductus, as corrected by that of the aortic isthmus, was abnormally small in 47 rats (72%). The rat fetuses with a septal defect or abnormal myocardial architecture, or both, usually had a small ductus; it was very small or absent in those fetuses with tetralogy of Fallot. Of the four fetuses with truncus arteriosus, two had a vestigial vasculature on the truncus root and three had a rudimentary infundibulum. CONCLUSIONS: The cardinal defect may be the anomalous and reduced development of the sixth arch arteries, which by imposing pressure overload on the fetal right ventricle, may have led to either or both the persistence of ventricular septal defect as a vent or the formation of myocardial architecture favorable for the generation of pressure in the right ventricle. PMID- 8436761 TI - Computational structural analysis based on intravascular ultrasound imaging before in vitro angioplasty: prediction of plaque fracture locations. AB - OBJECTIVES: This in vitro study was designed to test the hypothesis that a structural analysis based on intravascular ultrasound images of atherosclerotic vessels obtained before angioplasty can be used to predict plaque fracture locations and balloon pressures required to cause fracture. BACKGROUND: Intravascular ultrasound imaging performed before interventional procedures has potential for providing information useful for guiding therapeutic strategies. METHODS: Intravascular imaging was performed on 16 atherosclerotic human iliac vessel segments obtained freshly at autopsy; balloon angioplasty was then performed with 1-min inflations at 2 atm, increasing in 2-atm increments until fracture of the lumen surface occurred. Fracture locations were confirmed by histopathologic examination. Structural analysis of these images was performed with a large strain finite element analysis of the image that calculated the distribution of stress in the vessel with 2 atm of lumen pressure. RESULTS: Structural analysis demonstrated a total of 30 high circumferential stress regions in the vessels (mean 1.9 high stress regions/vessel). A total of 18 plaque fractures occurred in the 16 vessel segments. Of the 17 fractures that occurred in the 15 specimens with regions of high circumferential stress, 14 (82%) occurred at a high stress region (p < 0.0001). However, there was no significant relation between the peak stresses estimated by structural analysis and the ultimate balloon inflation pressure required to cause fracture. CONCLUSIONS: Structural analysis based on intravascular ultrasound imaging performed before in vitro balloon angioplasty can predict the locations of plaque fracture that usually accompany angioplasty. However, these data suggest that intravascular ultrasound may not be useful for predicting the ultimate balloon inflation pressure necessary to cause fracture, possibly because of the variable fracture properties and microscopic structure of atherosclerotic tissues. PMID- 8436762 TI - Measurement from arteriograms of regional myocardial bed size distal to any point in the coronary vascular tree for assessing anatomic area at risk. AB - OBJECTIVES: To obtain the size of regional myocardial mass for individual coronary arteries in vivo. BACKGROUND: The anatomic site of occlusion in a coronary artery does not predict the size of the risk area because location of the occlusion does not account for the size of the artery or of its dependent myocardial bed. METHODS: Intracoronary radiolabeled microspheres were injected and coronary arteriograms were quantitatively analyzed by semiautomated methods. The coronary artery lumen areas and the sum of epicardial coronary artery branch lengths distal to the points where radiomicrospheres had been injected were determined from both in vivo and postmortem coronary arteriograms. Regional myocardial mass distal to the point of each microsphere injection was correlated with corresponding distal summed coronary branch lengths and with coronary artery lumen areas. RESULTS: 1) Regional myocardial mass was closely and linearly related to sum of coronary artery branch lengths distal to any point in the coronary artery tree and therefore could be determined for any location on a coronary arteriogram. 2) The fraction of total left ventricular mass at risk distal to a stenosis could be determined from the corresponding fraction of total coronary artery tree length independently of the scale or X-ray magnification used to measure absolute branch lengths. 3) Cross-sectional lumen area at any point in the left coronary artery tree was closely related to the size of the dependent vascular bed with a curvilinear relation similar to that observed in humans with normal coronary arteriograms. CONCLUSIONS: On coronary arteriograms, the anatomic area at risk for myocardial infarction distal to any point in the coronary artery tree can be determined from the sum of distal coronary artery branch lengths. There is a curvilinear relation between coronary artery lumen area and dependent regional myocardial mass comparable to that in humans, reflecting fundamental physical principles underlying the structure of the coronary vascular tree. PMID- 8436763 TI - Regional changes in blood flow, extracellular potassium and conduction during myocardial ischemia and reperfusion. AB - OBJECTIVES: We postulated that ventricular arrhythmias may arise from the heterogeneous washout of ischemic metabolites. Our objective was to investigate the distribution of extracellular potassium concentration ([K+]o) during myocardial ischemia and reperfusion and to correlate this distribution with regional differences in myocardial blood flow. BACKGROUND: Our previous study showed that reperfusion after a brief period of ischemia resulted in heterogeneous reflow of the ischemic myocardium. METHODS: The changes in regional myocardial blood flow, midmyocardial [K+]o and electrogram duration were quantitated in 14 dogs undergoing 20 min of left anterior descending coronary artery occlusion and 1 min of reperfusion. Regional myocardial blood flow was measured by using 15-microns radioactive microspheres in 1- to 1.5-g full thickness myocardial samples. The [K+]o was measured with intramyocardial K(+) sensitive electrodes. RESULTS: During coronary occlusion, the ischemic zone exhibited a reduction in regional blood flow to 0.13 +/- 0.06 ml/g per min and increases in [K+]o to 9.3 +/- 2.6 mmol/liter and electrogram duration to 131.8 +/ 38.6% of control. Heterogeneous reduction in regional blood flow at various sites in the ischemic zone had fair correlations with variable increases in [K+]o (r = -0.70) and electrogram duration (r = -0.75). During min 1 of reperfusion, regional blood flow ranged from two to more than seven times baseline, resulting in a disorganized spatial distribution of perfusion with islands of high and low blood flows. Associated with the heterogeneous early reperfusion regional myocardial blood flow, [K+]o and electrogram duration changed at different rates toward normal. Whereas correlation between regional blood flow and [K+]o or standardized electrogram duration was fair during ischemia, this correlation was poor during early reperfusion. CONCLUSIONS: Spatial heterogeneity in regional myocardial blood flow during myocardial ischemia and early reperfusion is associated with heterogeneity in [K+]o and electrophysiologic characteristics, which in turn may play an important role in the genesis of arrhythmias arising from the ischemic and reperfused myocardium. PMID- 8436764 TI - Issues in contemporary cardiac rehabilitation: a historical perspective. AB - Cardiac rehabilitation consists of exercise, psychosocial support and education and is prescribed most often for patients with coronary heart disease. Its purpose is to facilitate readaptation to normal life through the achievement of maximal functional capability and to reduce heart disease risk factors. It began historically with progressive ambulation after myocardial infarction and by 1980 became a standardized inpatient therapy performed according to a stepped procedure. Predischarge exercise testing was added and has become a meaningful contribution to the concept of risk stratification after an acute coronary event. Rehabilitation has subsequently become part of the outpatient environment and is delivered by multiple models. Meta-analyses have shown that rehabilitation reduces overall and cardiovascular deaths by about 20% and sudden death by about 37% during the year after an acute myocardial infarction. The significance of this, however, must now be modulated by the dynamic role of aggressive coronary intervention. Selection for such intervention has become an important adjunctive aspect of rehabilitation. Newer findings suggest that those stratified at low risk will benefit most by the modification of coronary risk factors, and that patients previously thought to be poor candidates for rehabilitation (such as those with significant left ventricular dysfunction and low work capacity) may experience substantial relative functional benefit. Beyond risk stratification, important contemporary issues include surveillance of patients after angioplasty, the effectiveness of rehabilitation in the attenuation or reversal of both native and vein graft atherosclerosis and consideration of such currently emphasized end points as quality of life and economic evaluation. PMID- 8436765 TI - It is all in the numbers. PMID- 8436766 TI - Emergence of the cardiologist-entrepreneur. PMID- 8436767 TI - A prescription for the ACC health policy process. PMID- 8436768 TI - Infarct transmurality, Q waves and ventricular remodeling. PMID- 8436769 TI - Food antigen-induced lymphocyte proliferation in children with atopic dermatitis and food hypersensitivity. PMID- 8436770 TI - Quantifying platelet-activating factor in biologic systems. PMID- 8436771 TI - Intestinal reactivity in allergic and nonallergic patients: an approach to determine the complexity of the mucosal reaction. AB - BACKGROUND: To determine whether inflammatory markers and mediators were released in response to different intestinal antigens, studies were performed in atopic patients allergic to birch, patients allergic to psyllium powder (ispaghula), and patients intolerant to milk. METHODS: Allergy to birch and psyllium powder was documented by the presence of circulating IgE antibodies and positive skin tests. Patients intolerant to milk had negative outcomes of radioallergosorbent tests and skin tests but positive results of double-blind, placebo-controlled tests. Challenge of the intestine with different antigens was achieved by perfusion of a jejunal segment occluded between balloons. Basal and antigen-activated release of mast cell/basophil and eosinophil products and of substances emanating from the plasma and interstitial fluid was compared in perfusate fluid from patients (n = 8) and matched healthy controls (n = 8). RESULTS: Perfusate levels of albumin and hyaluronan (previous name hyaluronic acid) were increased threefold to fivefold by antigen in all patients, but not in controls. Eosinophilic cationic protein increased in patients but also in ispaghula controls. Histamine was released in response to milk, but not in patients allergic to birch or ispaghula. Prostaglandin E2 increased in milk- and birch-sensitive patients. In response to ispaghula, however, it was released in both patients and controls. CONCLUSIONS: We conclude that subclinical intestinal challenge with antigen induces an increase in the appearance rate of albumin and hyaluronan in the intestinal lumen both in atopic patients (with target organs such as the lungs or nose and eyes) and in patients with intestinal intolerance to milk. These changes in permeation are similar to those reported from other organs such as the lung. They may reflect a common response in early phase I reactions that are either IgE-mediated or occur in response to food antigens without any obvious involvement of an IgE mediated mechanism. Subclinical provocation with intestinal antigens should prove useful for further elucidation of mechanisms underlying intestinal mucosal reactions to exogenous stimuli. PMID- 8436773 TI - Association of ocular cataracts with inhaled and oral steroid therapy during long term treatment of asthma. AB - BACKGROUND: Posterior subcapsular cataracts (PSCs) have been reported to occur in some asthmatic patients treated with inhaled steroids. METHODS: We studied the associations between the occurrence of PSCs and inhaled and oral steroid therapy in 48 adults in a cross-sectional survey by slit lamp. Accurate records of the patients' long-term usage of these drugs were available: 9.2 +/- 5.2 years for inhaled steroid and 9.1 +/- 9.3 years for prednisone (mean +/- SD). Their current inhaled steroid dosage averaged 1.46 +/- 0.85 mg/day (range, 0 to 3.2 mg/day). RESULTS: Twenty-seven percent of the group had PSCs. The occurrence of PSCs correlated with the current daily dose and duration of prednisone use (p = 0.002 and p = 0.01, respectively), but not with the dose or duration of inhaled steroid treatment. As judged by multiple logistic regression analysis, neither the particular inhaled steroid drug used, nor its daily dose or cumulative dose, nor the additional nonsteroidal risk factors for PSCs also present in some of these patients contributed significantly to their risk of developing PSCs. CONCLUSIONS: The findings do not exclude the possibility that inhaled steroid therapy might lead to PSCs if a person has an exceptionally high inherent susceptibility. However, in the asthmatic population at large, the risk appears negligible, even if high doses of inhaled steroid are administered. PMID- 8436772 TI - Interpretation of skin tests to house dust mite and relationship to other allergy parameters in patients with asthma and chronic obstructive pulmonary disease. The Dutch CNSLD Study Group. AB - BACKGROUND: The relationships between allergic symptoms after exposure to house dust, allergy parameters (skin test to house dust mite [HDM], total IgE, HDM specific IgE, and blood eosinophil counts), and several confounding variables (age, sex, smoking habits, and airway hyperresponsiveness) were evaluated in 235 patients with asthma and chronic obstructive pulmonary disease (COPD). RESULTS: Skin tests had higher diagnostic value (sensitivity plus specificity) for symptomatic allergy than specific IgE (1.45 versus 1.36) or total IgE (1.16). The other allergy parameters gave no additional information on symptoms once the skin test was known. Expressing the skin test relative to the histamine control proved slightly better than uncorrected wheal size, but this probably has limited clinical value. The best cutoff level for a positive skin test was 0.7 when the histamine wheal size was accounted for by division, -6 mm when subtraction was used, and 7 mm for absolute wheal size. These cutoff levels proved equally applicable in various subgroups of patients with asthma and COPD. Only the skin test and female sex were independent predictors of allergic symptoms. CONCLUSION: We conclude that skin tests to HDM are better predictors for clinical allergy than total or specific IgE levels and eosinophil count, and that they are applicable in most patients with asthma and with COPD. PMID- 8436774 TI - Nasal secretions in response to acetylsalicylic acid. AB - BACKGROUND: Acetylsalicylic acid (ASA) induces rhinorrhea in a subset of patients with asthma or chronic rhinosinusitis or both and nasal polyps. The underlying mechanism of the reaction is obscure. METHODS: To assess the nasal response to ASA challenge, four groups of patients were challenged orally with ASA: group A (10 ASA-sensitive patients); group B (nine patients with nasal polyps and histories of tolerance to ASA); group C (nine ASA-tolerant patients with chronic allergic rhinitis); and group D (eight healthy nonatopic subjects). RESULTS: Nasal lavages obtained before and after ASA challenge were assayed for proteins (total protein, lactoferrin, lysozyme, albumin) and inflammatory mediators (histamine, prostaglandin D2, and leukotriene C4). ASA challenges induced severe rhinorrhea and congestion and significant increases in mean concentrations of all measured nasal proteins in group A. Histamine and prostaglandin D2 rose, but not significantly. In the two control groups with chronic rhinitis, ASA induced increases in the concentration of proteins and histamine. Leukotriene C4 concentrations were significantly elevated in nasal lavages after ASA challenge in groups A and C only. In group D no symptoms or changes in nasal proteins were observed after aspirin challenge. CONCLUSIONS: These observations suggest that production of lipoxygenase products of arachidonate may induce glandular secretions that may participate in the clinical changes associated with ASA sensitivity. PMID- 8436775 TI - Influence of oral calcium medication on nasal resistance in the nasal allergen provocation test. AB - Although calcium has been used for several decades to treat allergic diseases of the skin and respiratory tract, controlled studies demonstrating the action of oral preparations in allergic rhinitis are lacking. This placebo-controlled, double-blind, crossover study shows that 1000 mg calcium administered orally significantly inhibits the allergen-induced swelling of the nasal mucosa in the allergen provocation test. Sneezing and secretion, which are allergic symptoms, were not reduced. This study is the first to confirm the positive effect of oral calcium on a symptom of allergic rhinitis. PMID- 8436776 TI - Eosinophils in nasal polyps and nasal mucosa: an immunohistochemical study. AB - Immunohistochemical staining was performed at the time of endoscopic sinus surgery (ESS), after 6 months, and after 1 year on nasal polyps and biopsy specimens of the macroscopically unaffected mucosa of the middle and inferior turbinate bones of 46 patients with nasal polyps. During the follow-up period the patients were treated with topical corticosteroids. At time of ESS significantly more BMK13+ and EG1+ (pan eosinophil markers) and EG2+ (activation marker) eosinophils were found in the polyps than in the macroscopically unaffected mucosa of the middle and inferior turbinate bones of the patients. In the middle and inferior turbinate bones of 10 healthy subjects no EG2+ (activated) eosinophils were detected, whereas low-to-moderate numbers of BMK13+ and EG1+ eosinophils were seen in these specimens. This emphasizes that eosinophils play a role in the pathogenesis of nasal polyps. Compared with numbers at ESS, after 6 months and 1 year of follow-up, lower numbers of BMK13+, EG1+, and especially of EG2+ eosinophils were found in recurrences of polyps and in the macroscopically unaffected mucosa of the middle and inferior turbinate bones of the patients. The decrease in number of EG2+ (activated) eosinophils is an indication of a reduced local inflammatory reaction, and could be an important factor in postponement of recurrences of nasal polyps. PMID- 8436777 TI - Effect of inhaled corticosteroids on peripheral blood eosinophil counts and density profiles in asthma. AB - BACKGROUND: Inhaled corticosteroids are effective in the treatment of asthma and reduce bronchial hyperresponsiveness. We examined the effect of inhaled budesonide (1600 micrograms/day for 14 days) on the number and density profile of peripheral blood eosinophils in 10 patients with mild stable asthma in a double blind, placebo-controlled, crossover trial. METHODS: At the end of each study period, blood was collected immediately before measurement of bronchial responsiveness calculated as the concentration of methacholine causing a 20% fall in forced expiratory volume in 1 second (PC20). Plasma leukocyte suspension obtained after sedimentation of blood with 46% dextran was layered on a Percoll continuous-density gradient. After centrifugation, 20 sequential aliquots of increasing density gradients were removed for differential counts. Eosinophils recovered from density of gradients less than 1.080 gm/ml were defined as hypodense. RESULTS: Budesonide treatment resulted in a fall in mean eosinophil count from 0.37 +/- 0.05 x 10(9) L-1 after placebo to 0.16 +/- 0.03 x 10(9) L-1 (p < 0.01). A significant reduction occurred in the hypodense eosinophil population from 51.6% +/- 4.3% after placebo to 38.1% +/- 3.1% after budesonide (p < 0.05). Mean log PC20 increased from -0.26 +/- 0.12 after placebo to -0.004 +/- 0.14 after budesonide (p < 0.01). CONCLUSION: We conclude that inhaled steroid therapy reduces the number of circulating hypodense eosinophils, which is an effect that may underlie the improvement in bronchial hyperresponsiveness. PMID- 8436778 TI - Increased plasma platelet-activating factor in children with acute asthmatic attacks and decreased in vivo and in vitro production of platelet-activating factor after immunotherapy. AB - BACKGROUND: To explore the possible role of platelet-activating factor (PAF) in the pathogenesis of bronchial asthma, circulating PAF and in vitro production of PAF were studied. METHODS: Radioimmunoassay kits were used in 15 children with acute asthmatic attacks, in 25 newly diagnosed asthmatic children, in 25 good and 18 poor responders to immunotherapy, and in 18 healthy controls. RESULTS: The results demonstrated the following: (1) PAF was present in the blood of healthy controls. (2) New patients had much higher circulating PAF than did healthy controls (p < 0.005), and the circulating PAF decreased after immunotherapy in good (p < 0.005) but not in poor responders. (3) The circulating PAF increased up to 20 times that of healthy controls during acute asthmatic attacks. (4) The spontaneous and allergen-stimulated secretion of PAF were markedly increased in new patients and decreased to normal after successful immunotherapy (p < 0.005). (5) No increased spontaneous and allergen-stimulated production of PAF was found during acute attacks, but granulocytes from those patients still produced the greatest amount of PAF when stimulated with calcium ionophore A23187. (6) Although a major portion of allergen-induced PAF was secreted, less than 10% of ionophore-induced PAF was secreted. CONCLUSION: The findings that the circulating PAF increased markedly during acute asthmatic attacks and the enhanced in vivo and in vitro productions of PAF decreased to normal after successful immunotherapy strongly suggest that PAF may be involved in the pathogenesis of bronchial asthma. PMID- 8436779 TI - The role of T lymphocytes in patients with food-sensitive atopic dermatitis. AB - The role of T lymphocytes was assessed in patients with food-sensitive atopic dermatitis (AD). T lymphocytes plus monocytes responded well to ovalbumin or bovine serum albumin (BSA) in children with AD who were sensitive to hen's egg or cow's milk compared with healthy children and children with immediate allergic symptoms who are sensitive to hen's egg or cow's milk. The responding cells were shown to be predominantly CD4+ T lymphocytes. Interleukin-2 activity and interferon-gamma concentrations in culture supernatants of ovalbumin-stimulated peripheral blood mononuclear cells (PBMCs) from patients with AD who were sensitive to hen's egg were significantly higher than those of healthy children and patients sensitive to hen's egg with immediate symptoms. Expression of Fc epsilon R II on B lymphocytes in cultures of ovalbumin-stimulated PBMCs from patients with AD was significantly higher than that of healthy children, but it tended to be lower than that of patients with immediate symptoms. These results suggest that, in patients with AD who are food sensitive, CD4+ T lymphocytes stimulated by food antigens secrete lymphokines such as interleukin-2 and interferon-gamma that are secreted from TH1 clones in mice, and express Fc epsilon R II on B lymphocyte that is induced by interleukin-4 secreted from TH2 clones in mice. Taken together, cell-mediated immunity may also occur in addition to IgE-mediated hypersensitivity in patients with food-sensitive AD. PMID- 8436781 TI - Nasal candidiasis in a patient on long-term topical intranasal corticosteroid therapy. PMID- 8436780 TI - Effect of elimination diets on food-specific IgE antibodies and lymphocyte proliferative responses to food antigens in atopic dermatitis patients exhibiting sensitivity to food allergens. AB - Peripheral blood mononuclear cells (PBMCs) from patients with atopic dermatitis (AD) selected as being sensitive to hen's egg or cow's milk responded to food antigens, ovalbumin, or bovine serum albumin, with significantly enhanced DNA synthesis compared with the DNA synthesis in PBMCs from nonatopic control subjects and food-sensitive patients with immediate symptoms. Patients were treated with elimination diets. Symptoms of AD had been in remission during elimination diets. The levels of specific IgE antibodies to hen's egg or cow's milk decreased during elimination diets in patients with positive radioallergosorbent test (RAST). In patients with negative RAST, specific IgE antibodies remained negative during elimination diets. The proliferative responses of PBMCs to food antigens also decreased during elimination diets in patients with proliferative responses before elimination diets. Taken together, specific IgE antibodies to food antigens are useful indexes of the effect of elimination diets in food-sensitive patients with AD and positive RAST, and proliferative responses of PBMCs to food antigens are useful indexes of the effect of elimination diets in food-sensitive patients with AD and proliferative responses of PBMCs. PMID- 8436782 TI - Allergy and desensitization to zidovudine in patients with acquired immunodeficiency syndrome (AIDS). PMID- 8436783 TI - Hydroxyzine for interstitial cystitis. PMID- 8436784 TI - Hypersensitivity pneumonitis in a soy sauce brewer caused by Aspergillus oryzae. PMID- 8436785 TI - Safety and efficacy of cromolyn sodium and inhaled corticosteroids. PMID- 8436786 TI - Morrow-Brown needles revisited. PMID- 8436787 TI - Women promoting women's health. PMID- 8436788 TI - Workshops. PMID- 8436789 TI - Glasgow Essay Award. PMID- 8436790 TI - A longitudinal study of sex differences in how physicians relate to dying patients. AB - The authors were interested in whether or not there were sex differences in the way physicians respond to the needs of dying patients and their families at the time they graduate from medical school versus ten years later. A 71% return rate was received from a questionnaire mailed in 1976 to 1,540 graduates of five selected medical schools; the return rate for the follow-up study in 1986 was 58%. Ten percent of the respondents were female. The 1976 findings provided some evidence to support the argument that there are differences between male and female physicians' attitudes toward dying patients soon after graduation. The 1986 data, gathered after a decade of practicing medicine, showed even more striking differences. Perhaps "feminine characteristics" lend themselves to better communication with dying patients and their families than "masculine traits" do. PMID- 8436791 TI - Breast cancer. PMID- 8436792 TI - Anorexia nervosa visited and revisited: weight is the issue. AB - Anorexia nervosa is known as a psychiatric disorder. Many practitioners seem unaware that a patient in a starvation state is cognitively impaired and thus a poor candidate for psychotherapy. Weight restoration is a prerequisite to other treatment modalities. Many practitioners and all patients fail to recognize this illness because of a prevailing cultural idealization of thinness. Since these patients initially seem so compliant in treatment, valuable time is lost by those who fail to understand the patient's deceptiveness and the life-threatening potential of the disease. PMID- 8436793 TI - Women, eating disorders, and society. PMID- 8436794 TI - Inaugural address: mentors and role models. PMID- 8436795 TI - Pinhole eyewear systems: a special report. AB - Multiple pinhole discs are being promoted as part of systems claimed capable of correcting refractive error. Attempts to mitigate refractive error utilize training attributable to the systems of Bates, Peppard, and Huxley. The pinhole discs provide an array of 0.9mm apertures separated by 3mm horizontally and vertically. Because of the small aperture size, some of the optical advantages of the pinhole are offset by diffraction effects. The discs can produce multiple images and the visual experience of individuals will be a function of the user's pupil size and refractive error. These are discussed both theoretically and based on the author's observations wearing the spectacles. PMID- 8436796 TI - State board requirements for CPR certification for licensure in independent health professions. AB - CPR certification requirements for licensure were obtained from 50 states and the District of Columbia for the fields of medicine, osteopathy, podiatry, chiropractic, dentistry, and optometry. It was found that none of the states required CPR certification for initial medical, osteopathic or chiropractic licensure or license renewal, while 4 percent required certification for initial podiatric licensure and license renewal. For initial licensure in dentistry, 25 percent of the boards required CPR certification while 29 percent required CPR certification to renew dental licensure. For initial optometric licensure with diagnostic pharmaceutical agents, 44 percent of the states required CPR certification. PMID- 8436797 TI - Visual field loss secondary to radiation-induced cerebral necrosis. AB - Radiation-induced cerebral necrosis has been well documented in the literature. Because radiation induced cerebral necrosis can occur to any part of the central nervous system that falls within the irradiated area, the visual pathway is highly susceptible to damage as it passes from the eye to the visual cortex. With proper visual field testing and interpretation, optometrists may serve as primary diagnosticians in radiation-induced cerebral necrosis and actively participate in the long-term management of these patients. This case presents a patient with visual field loss secondary to a temporal lobe lesion whose etiology was thought to be radiation-induced. The incidence, pathophysiology, and clinical features of radiation-induced cerebral necrosis as well as other differential diagnoses are discussed. PMID- 8436798 TI - National Practitioner Data Bank. AB - Recently the federal government started keeping records relating to the conduct and competence of doctors. This article will discuss the National Practitioner Data Bank and how it relates to optometry. Potential problems are raised by the author while the need and benefits of such a program are left for future discussion. PMID- 8436799 TI - Treatment of retinal hemangiomas with dye yellow laser. AB - Retinal capillary hemangioma (angiomatosis retinae; von Hippel's disease) is a relatively uncommon vascular tumor. When seen in association with systemic angiomas, it is known as von Hippel-Lindau disease. Untreated, these tumors can cause numerous sight threatening sequelae, including exudative and tractional retinal detachment. Recently, the dye yellow laser has been demonstrated to be a safe and effective method of ablating retinal hemangiomas. This paper discusses the case of a retinal hemangioma that was successfully treated with the dye yellow laser. The current treatment modalities of retinal hemangiomas are reviewed, as well as recent literature on the tunable organic dye laser and its utilization in the treatment of retinal vascular disorders. PMID- 8436800 TI - The list for today. PMID- 8436801 TI - Characteristics of optometric practices that provide pro bono optometric care to migrant farm workers and other indigent groups. PMID- 8436802 TI - Melanocytoma of the optic disc. AB - The common perception that melanocytomas of the optic disc do not affect visual function is one that must be challenged. We report two cases of melanocytoma of the optic disc that show that visual function can be significantly affected. The benign nature of optic disc melanocytomas in contrast to the urgency needed in optic nerve malignant melanomas makes the differential diagnosis even more critical. In addition, recent reports have documented malignant transformation of melanocytomas. Therefore, close observation and proper diagnostic work-up of any suspicious optic nerve head tumor is essential. PMID- 8436803 TI - Role of vasoconstrictor tone in arterial pressure lability after chronic sympathectomy and sinoaortic denervation in rats. AB - In both chronically sympathectomized (SNX) and sinoaortic denervated (SAD) rats, removal of vasoconstrictor influences decreases mean arterial pressure (MAP) and its variability in parallel. This study examined if this decrease in arterial pressure lability is solely a result of decreasing vascular tone. In conscious 14 week-old male sympathectomized (guanethidine at 1-13 weeks of age) and sinoaortic denervated (2 weeks before study) rats, arterial pressure was recorded beat-to beat during 30-min consecutive periods; control; ganglionic blockade in sinoaortic denervated rats and angiotensin converting enzyme inhibition plus vasopressin antagonism in sympathectomized rats; and restoration of the initial arterial pressure with continuous infusions of phenylephrine and angiotensin II. Sympathectomized and, even more, sinoaortic denervated rats had increased pressure variability. Neural or humoral blockade markedly reduced arterial pressure and its liability in both groups of rats and subsequent restoration of the arterial pressure with vasoconstrictor infusions returned lability to levels either slightly above (sympathectomy) or below (sinoaortic denervation) control values. In basal conditions, an increased frequency of occurrence of depressor episodes was evidenced in sympathectomized rats whereas a variable ratio of pressor to depressor events was observed in sinoaortic denervated rats. During vasoconstrictor infusions, blood pressure lability was mainly due to depressor events in both groups of rats. It is concluded that the background vascular tone provided by endogenous pressor systems is necessary for the expression of the depressor component of blood pressure lability in sinoaortic denervated and in sympathectomized rats. The study also suggests that in sympathectomized rats, humoral influences act to limit rather than enhance blood pressure lability, whereas in sinoaortic denervated rats, the sympathetic nervous system may directly generate part of the lability. PMID- 8436804 TI - Glucose-induced ion secretion in rat jejunum: a mucosal reflex that requires integration by the myenteric plexus. AB - We tested the hypothesis that the mucosa of rat jejunum is stimulated by intraluminal D-glucose, resulting in nerve-mediated ion secretion. We examined the D-glucose-induced secretory response in two ways. First, we measured the unidirectional fluxes of sodium and chloride ions, in vivo, during perfusion of segments of jejunum with solution that contained either D-glucose or mannitol. Second, we measured the net rate of absorption of D-glucose from sodium-free solution; this parameter is related to the rate of sodium ion secretion. We used the above two approaches in conjunction with techniques for destroying specific subsets of the intestinal nerves. Thus, we evaluated the subset of intestinal nerves that integrates the secretory response of the mucosa to D-glucose. Jejunal segments perfused with D-glucose solution exhibited significantly greater rates of sodium and chloride ion secretion than did segments perfused with mannitol. Intestinal segments in which the myenteric nerve plexus had been destroyed exhibited a significantly lower rate of sodium ion secretion in the presence of D glucose than was seen in fully innervated segments. A role for the myenteric nerves in D-glucose-induced ion secretion was also indicated by experiments that involved absorption of D-glucose from sodium-free solution. It was concluded that exposure of the mucosa of rat jejunum to glucose increases the rate of secretion of both sodium and chloride ions. The myenteric nerve plexus is apparently involved in the integration of this mucosal reflex. PMID- 8436805 TI - Cardio-respiratory control in an infant with Ondine's curse: a multivariate autoregressive modelling approach. AB - We applied spectral analysis through multivariant autoregressive model fitting [1] to RR interval (RRI) and respiratory (RES) oscillation obtained during quiet sleep in an infant with congenital central hypoventilation syndrome (Ondine's curse), a child with obstructive sleep apnea, and two healthy children. Power spectra, impulse response and noise contribution ratio between RRI and RES oscillation were calculated by using a minicomputer PFU-1200 (FACOM) to determine the structure of the feedback system between RRI and RES within the central nervous system. We found that the respiratory noise contribution ratio to RRI was significantly smaller in Ondine's curse (37 +/- 7.7%, at 0.23 Hz) than in obstructive sleep apnea (90 +/- 6.7%, at 0.39 Hz) and healthy subjects. We postulate that the result shows disturbance of the central autonomic control of breathing and heart rate in Ondine's curse. PMID- 8436806 TI - Can the 5-HT2/1c agonist DOI cause differential sympatho-excitation in nerves supplying the heart in anaesthetized cats? AB - A comparison of the effects on sympathetic nerve activity to the heart of intravenous administration of the selective 5-HT2/1c agonist 1-(2,5-dimethoxy-4 iodophenyl)-2-aminopropane (DOI) alone and in the presence of the peripherally acting 5-HT2/1c antagonist BW501C67 were made in alpha-chloralose anaesthetized cats. Activity in both cardiac sympathetic nerves running in the vagus and in both inferior cardiac nerves was simultaneously recorded. In addition renal and phrenic nerve activity, heart rate, arterial blood pressure, femoral arterial flow and tracheal pressure were also recorded. DOI evoked a rise in blood pressure and increased femoral arterial resistance in both groups of animals. In the BW501C67 pretreated animals, DOI had no effect on heart rate but caused a significant increase in all sympathetic nerve activities. In non-pretreated animals, however, the rise in blood pressure was associated with variable effects on sympathetic nerve activity, a significant rise only occurring in renal nerve activity. In these experiments DOI evoked a bradycardia. The variability in sympathetic nerve activity in the non-pretreated animals may have resulted from the rise in blood pressure evoking a baroreceptor-mediated central sympathoinhibition which would interfere with the central sympathoexcitatory effects of DOI. It is concluded that centrally, DOI will cause sympathoexcitation. In addition, intravenous DOI acting on 5-HT2 receptors on bronchial smooth muscle evokes bronchoconstriction as indicated by the very large rise in tracheal pressure in non-BW501C67-pretreated animals. If not controlled this severely compromises respiration leading to a large overestimate of the sympathoexcitatory effects of stimulation of central 5-HT2/1c receptors. PMID- 8436807 TI - Cardiovascular responses of conscious rats to carotid body chemoreceptor stimulation by intravenous KCN. AB - In the present study we analyzed the cardiovascular, respiratory and behavioral responses evoked in rats by KCN. Hypertension, hyperpnea and alerting behavior were characteristic responses in unanesthetized animals. Selective denervation of aortic and carotid bifurcation areas confirmed the carotid body chemoreceptor (CBC) origin of these responses. Sino-aortic denervation, as well as selective carotid sinus denervation abolished the responses, while, after selective aortic denervation, the responses were not different from those of the control rats. The administration of prazosin abolished the hypertensive response but did not change the bradycardic response, whereas the administration of atropine eliminated the bradycardic response and potentiated the hypertensive response to KCN. Increasing doses of KCN (10-80 micrograms/rat) produced proportionally larger bradycardia, hypertension and hyperventilation. Slight attenuation of bradycardic responses to KCN were observed in rats under chloralose anesthesia, while marked depression of bradycardic responses were observed under pentobarbitone anesthesia. Both anesthetics changed the hypertensive responses to hypotensive responses. In conclusion, the cardiovascular, respiratory and behavioral responses to intravenous KCN are a good functional test to CBC stimulation in unanesthetized rats, producing simultaneously intense bradycardia with hyperventilation and behaviour responses. PMID- 8436808 TI - Social control doctrines of mental illness and the medical profession in nineteenth-century America. AB - Social control doctrines of mental disorders have influenced a generation of psychologists and have shaped attitudes and discussions about how to treat the mentally ill. In light of the failure of deinstitutionalization as a public policy and the contemporary concern with the medical or biological bases of psychiatric disorders, this paper re-examines social control doctrines. Reviewing mid-nineteenth century statistical accounts, the author challenges claims of social control theorists and shows that in recent years some former social control advocates and revisionists have "recanted" and criticized their earlier use of the concept of social control, particularly the characterization of the asylum as a "total institution." PMID- 8436809 TI - Educated insane: a nineteenth-century psychiatric paradigm. AB - In the 1830s the time-honored notion that excess study could lead to madness underwent a significant change in America. Under the influence of Enlightenment pedagogy and phrenology, influential superintendents like Amariah Brigham and Isaac Ray feared that the "unnatural" overstimulation of children in schools would ruin their development. In the second half of the nineteenth century, as belief in environmental determinism waned and assumptions about what is "natural" changed, this psychiatric etiology was debated; then, overthrown. By the turn of the century, education was thought to aid, not harm, the mentally ill. PMID- 8436810 TI - B cell tolerance induction by cross-linking of membrane IgM, but not IgD, and synergy by cross-linking of both isotypes. AB - Previous studies in our laboratory demonstrated that overnight exposure of adult splenic B cells to anti-Ig resulted in an unresponsive state characterized by decreased antibody synthesis but normal mitogen-driven proliferation (i.e., energy). Because both anti-F(ab')2 and anti-mu were equally effective at inducing tolerance, it was important to determine whether cross-linking of IgD together with or separately from IgM influenced the induction of unresponsiveness. Although anti-mu induced significant unresponsiveness, treatment of adult splenic B cells with anti-delta alone generally failed to reduce the subsequent response to either LPS or fluoresceinated Brucella abortus. Interestingly, anti-delta synergized with suboptimal concentrations of anti-mu to induce tolerance. Synergy could be observed in this system when anti-delta was added either simultaneously with or before (but not after) anti-mu; moreover, anti-delta was effective in a pretreatment (wash-out) protocol. To investigate the role of protein tyrosine kinase (PTK) activity in tolerance induction, splenic B cells were treated with tyrphostin before treatment with either anti-mu or anti-delta. We found that pretreatment with tyrphostin for 2 h before the addition of anti-mu prevented the induction of unresponsiveness with this antibody, whereas this PTK inhibitor facilitated tolerance when used with anti-delta treatment only. We propose that cross-linking of surface IgM directly or indirectly invokes a tyrphostin sensitive, PTK-dependent pathway leading to the early events in tolerance induction, which can be augmented under limiting conditions by anti-IgD. Because cross-linking of either receptor initiates several common pathways, simultaneous cross-linking can lead to synergy and a dominance of the IgM signal. In contrast, IgD alone may fail to elicit tolerance because this isotype may also be associated with different PTK that cause positive signaling. PMID- 8436811 TI - Effect of prostaglandin E2 (PGE2) on IL-3/granulocyte-macrophage colony stimulating factor production by T helper cells. Mode of stimulation and presence of costimulation can determine response to PGE2. AB - PGE2 is an immunomodulator that selectively inhibits the production of lymphokines associated with Th1 cells (IL-2 and IFN-gamma) but not Th2 cells (IL 4 and IL-5). We examined the effect of PGE2 on the production of IL-3 and granulocyte-macrophage (GM)-CSF from murine Th1 and Th2 clones. When the T cells were stimulated with Ag and APC, PGE2 inhibited IL-3/GM-CSF production from 3 Th1 clones and 1 Th2 clone, but enhanced production from 3 Th2 clones. A more specific bioassay demonstrated that IL-3 production was differentially affected by PGE2 in the Th clones. These data suggested that the effect of PGE2 on IL-3 production is dependent, not on a property of the lymphokine, but on a property of the T cell. The responsiveness to PGE2 did not consistently differ between Th1 and Th2 cells, and the observed heterogeneity in the response of Th2 clones did not correlate with the ability to induce increases in intracellular [Ca2+]. However, we postulated that signaling differences between the clones might explain the varied responsiveness to PGE2. If so, then the mode of stimulation might be expected to activate different pathways and thus affect the PGE2 responsiveness. Stimulation with ionomycin induced variable levels of IL-3/GM-CSF from the T cell clones. APC-derived costimulation dramatically enhanced IL-3/GM CSF; the cells which produced high levels in response to ionomycin alone were not detectably costimulating each other. Interestingly, PGE2 enhanced IL-3/GM-CSF (and IL-3 alone in at least some cases) from cells stimulated with ionomycin alone, demonstrating that the mode of stimulation affects the PGE2 responsiveness. Addition of APC not only enhanced lymphokine production, but also altered the PGE2-responsiveness of the Th1 cells. In these cells, PGE2 either inhibited IL-3 and GM-CSF production or had no effect, in no case was the lymphokine production enhanced by PGE2 as it had been with ionomycin alone. These data indicate that the presence of APC-derived costimulatory signals can alter the effect of PGE2 on Th cell lymphokine production. PMID- 8436812 TI - Impaired cell-mediated immunity in mice bearing healthy orthotopic corneal allografts. AB - A very high proportion of orthotopically grafted, histoincompatible corneas are accepted in healthy condition for prolonged intervals (> 8 weeks) by naive untreated BALB/c mice. Because these grafts form the anterior surface of the anterior chamber of the eye and because alloantigens placed in the anterior chamber elicit a deviant, stereotypic, systemic immune response known as anterior chamber-associated immune deviation, we have examined the state of alloantigen specific cell-mediated immunity in BALB/c mice with accepted corneal allografts, as well as mice that had rejected their corneal grafts. Attempts to induce alloantigen-specific delayed hypersensitivity (DH) by s.c. injections of lymphoid cells, genetically identical to the grafts, resulted in positive responses only in "rejector" mice; "acceptor" mice failed to develop or display DH. Spleens cells from acceptors and rejectors were then assayed for the ability to suppress local adoptive transfer of alloantigen-specific DH. It was found that transfer reactions failed to develop if spleen cells from acceptor mice were added to the inoculum, whereas spleen cells from rejected mice had no similar inhibitory effects. The suppression mediated by acceptor spleen cells in local adoptive transfer assays was determined to be specific for the alloantigens expressed on the long-standing corneal allografts. We conclude that, when orthotopic corneal allografts are accepted indefinitely by adult mice, graft success correlates with the induction of alloantigenically specific anterior chamber-associated immune deviation. It is proposed that suppression of alloantigen-specific DH, which is characteristic of mice with accepted grafts, plays a critical role in the success of grafted corneas. PMID- 8436813 TI - Regulation of protein kinase C isoform proteins in phorbol ester-stimulated Jurkat T lymphoma cells. AB - Activation of protein kinase C (PKC) in T cells leads to a variety of responses including IL-2 production and IL-2 receptor expression. PKC consists of several isoforms that exhibit some different in vitro properties. We have set up a Western blotting system to explore the regulation of PKC isoforms during T cell activation. In Jurkat T lymphoma cells, PKC alpha, beta, delta, epsilon, and zeta were detected. PKC alpha and beta existed primarily in the cytosol, translocated to the membrane fraction after 10 minutes of treatment with PMA, and almost completely disappeared within 16 h. A larger fraction of PKC delta and epsilon existed in the membrane fraction compared to PKC alpha or beta, and PKC epsilon translocated to the membrane fraction rapidly. Translocation of PKC delta was not apparent after 1 h treatment with PMA, but total PKC delta protein was reduced within 4 to 6 h of treatment. Consistent with this, overnight treatment with PMA caused down-regulation of both PKC delta and epsilon, but to a lesser degree than was observed with PKC beta. Anti-PKC zeta antibody detected two bands at 82 and 75 kDa. The 75-kDa band existed mostly in the cytosol fraction and showed no translocation or down regulation after PMA. We present evidence that this 75-kDa band represents PKC zeta. Similar PMA-induced translocation responses were observed in murine thymocytes showing that the responses are not unique to PKC isoforms in Jurkat. These results demonstrate that it is possible for the PKC isoforms to be differentially regulated during T cell activation. PMID- 8436814 TI - Direct demonstration of membrane IL-1 alpha on the surface of circulating B lymphocytes and monocytes. AB - A mAb against IL-1 alpha has been used in a high sensitivity immunofluorescence procedure to demonstrate directly the presence of surface IL-1 alpha on human monocytes and B cells from blood and tonsil. IL-1 alpha could be detected on monocytes and a subset (around 30%) of B cells without any in vitro activation. Although the subset of B cells expressing IL-1 alpha was distinct (i.e., the distribution of fluorescence intensity was bimodal), no correlation was seen with any other B cell subset marker in blood. In tonsil, IL-1 alpha was expressed by cells with a phenotype that suggested that they represented a subset of mantle zone B cells. Activation of tonsil B cells with anti-IgM, IL-4, IL-2, and mixtures of these reagents led to small increases in IL-1 alpha expression, as did activation of unfractionated tonsil cells with PHA. PMID- 8436815 TI - DNA regions flanking the mouse Ig 3' alpha enhancer are differentially methylated and DNAase I hypersensitive during B cell differentiation. AB - Two B cell-specific enhancer elements are associated with the IgH gene cluster. One enhancer is located within the J-C mu intron (E mu), whereas a second enhancer (3' alpha E) is approximately 12.5 kb 3' of the C alpha membrane exon. In an attempt to understand the function of 3' alpha E, we have characterized its surrounding structural milieu during various stages of B cell differentiation through analysis of methylation patterns and the identification of DNAse I hypersensitive sites. We observed a correlation between the chromatin structure of this region and the differentiation state of the cell. Compared to liver and brain, the region 3' of alpha was hypermethylated in pre-B and T cell lines and became progressively demethylated as B cell differentiation continued. A DNAse I hypersensitive site was present in pre-B cell lines about 17 kb 3' of 3' alpha E. In fully differentiated myeloma cell lines, a second cluster of DNAse I hypersensitive sites was present immediately 5' of 3' alpha E. Our data indicate that the 3' alpha enhancer is relatively sequestered during early stages of B cell differentiation and becomes increasingly accessible at later stages. PMID- 8436816 TI - Protease treatment of nuclear extracts distinguishes between class II MHC X1 box DNA-binding proteins in wild-type and class II-deficient B cells. AB - The X box region is critical for directing the expression of class II major histocompatibility complex genes in B lymphocytes. Although several class II promoter-specific DNA binding factors have been described, only the X box region factor, RFX, shows a genetic correlation with class II expression, being deficient in some B cell lines derived from patients with class II-deficient congenital immunodeficiency. To further evaluate the role of X box DNA-binding proteins in class II gene expression, the role of the X box region was examined in both class II-positive and -negative lymphoid cells. In addition to the wild type B cell line Raji, two class II transcriptional mutant cell lines, SJO and RJ2.2.5, and Jurkat, a class II negative T cell line, were examined. In contrast to wild-type B cells, neither of the class II mutant cell lines could use the X box region to direct the expression of a transiently transfected reporter gene, indicating that the X box-dependent transcriptional pathway is defective in these cells. The binding activity of the X1 box DNA-binding protein RFX was examined and found to be present in wild-type B cells and the mutant RJ2.2.5 but was absent in SJO and Jurkat. However, other X1 box-specific activities were detected in all these cell lines. To determine whether these different X1 box activities represented distinct DNA binding proteins or multimeric forms of the same factor(s), protease treatment of the crude nuclear extracts followed by DNA binding assays were carried out and demonstrated that B cell extracts contain at least two X1-specific factors. One of these cleaved products (band 1 pk) correlates with RFX activity. A similar comparison with protease-treated extracts prepared from Jurkat cells demonstrated the presence of the band 1pk activity despite an absence of the native RFX activity. In contrast, protease treatment and analysis of SJO extracts showed no detectable levels of the band 1pk activity. These results demonstrate that multiple X1 box-specific DNA-binding activities exist in all lymphoid cells, but the presence of an actively binding RFX species correlates with class II transcription. PMID- 8436817 TI - Verification of a model of a F(ab) complex with phenylarsonate by oligonucleotide directed mutagenesis. AB - A model of the combining site of a mouse antibody specific for p azophenylarsonate was tested by oligonucleotide-directed mutagenesis of the proposed hapten-contacting residues, Arg96 in the L chain, and Asn35, Trp47, Tyr50, Ser95, and Tyr100b in the H chain. The affinity and relative affinity for p-azophenylarsonate-N-acetyl-L-tyrosine of mutant antibodies expressed in transfectomas were determined by fluorescence quenching and by inhibition ELISA, respectively. The results show that alteration of the proposed contacting residues has drastic effects on hapten binding, and that the hydroxyl groups of Tyr50 and Tyr100b appear to orient the phenyl rings for optimal aromatic-aromatic interactions with the phenyl ring of the hapten. They further indicate a tight packing of the contacting residues around the hapten, which cannot accommodate changes in the positions of the functional groups of Asn35 and Ser95. PMID- 8436818 TI - Conservation of binding site geometry among p-azophenylarsonate-specific antibodies. AB - Murine A/J anti-p-azophenylarsonate mAb that express a dominant cross-reactive Id are encoded by a single set of germ-line VH and VL region genes. The crystal structure of the Fab of antibody 36-71, which uses this canonical set of genes but is somatically mutated, was previously determined. An Fab 36 71:phenylarsonate complex was modeled, identifying amino acid side chains that were proposed as contact residues to hapten. The remarkable conservation of these residues among canonical anti-p-azophenylarsonate antibodies suggested that the overall binding site geometry was maintained among somatically mutated antiarsonate monoclonal antibodies. To test this hypothesis, we used the germ line-encoded antibody 36-65 to construct mutant antibodies, using oligonucleotide directed mutagenesis, which differed only at the putative H chain hapten contacting residues, and measured their hapten binding. A framework residue at H chain position 47 involved in a hydrogen bond network with CDR residues was also mutated. Substitution of several amino acids at each position permitted evaluation of the stereochemical requirements for binding. The results indicate the importance of aromatic stacking of two H chain tyrosine residues against the phenyl ring of the hapten in maintaining affinity, as well as strict complementarity at H chain position 35. The results are consistent with the crystal model of the combining site, and provide further evidence for conservation of the three-dimensional binding site motif among antiarsonate antibodies that bear a dominant heritable ld. PMID- 8436819 TI - Production of transforming growth factor-beta by Mycobacterium avium-infected human macrophages is associated with unresponsiveness to IFN-gamma. AB - Transforming growth factor-beta 1 (TGF-beta 1) is a potent immunoregulatory molecule. It modulates production of cytokines, such as TNF-alpha and IL-6, and cell response to cytokine stimulation. Mycobacterium avium is an intracellular bacterium that multiplies within macrophages. The reason why M. avium can survive within macrophages is still unknown but probably is multifactorial. Exposure of M. avium-infected macrophages to rTGF-beta 1 before TNF stimulation significantly decreases the mycobactericidal/mycobacteriostatic activity associated with treatment with TNF. Infection of human monocyte-derived macrophages in vitro with M. avium strains belonging to serovars 1, 4, and 8 induced secretion of biologically active TGF-beta. The production of TGF-beta was strain dependent and was more pronounced in macrophages infected with virulent strains. Incubation of macrophages with M. avium-derived 33-kDa and 65-kDa proteins was associated with significant release of biologically active TGF-beta. Treatment of M. avium infected macrophages with rTNF-alpha in the presence of anti-TGF-beta 1 antibody induced significantly greater killing of M. avium than did treatment of macrophages with TNF-alpha in the absence of anti-TGF-beta 1 antibody. In addition, macrophage monolayers treated with anti-TGF-beta 1 antibody before infection with M. avium showed mycobactericidal activity after stimulation with rIFN-gamma; in contrast, no effect of IFN-gamma was seen in monolayers not treated with anti-TGF-beta 1 antibody. We conclude that TGF-beta 1 produced after M. avium infection is a potent inhibitor of macrophage activation by cytokines. This inhibition may have an important role in the regulation of the immune response against M. avium. PMID- 8436820 TI - Characterization of an unusual cell type (CD4+ CD3-) expanded by helminth infection and related to the parasite stress response. AB - Mice infected with the parasite Mesocestoides corti develop hypergammaglobulinemia, hepatomegaly, and splenomegaly. The immune response to M. corti infection is directed, in part, at molecules secreted by the organism. Two of these molecules have been shown to be hsp70 and hsp60 homologues. In this study it was found that incubation of splenocytes from infected animals with M. corti-secreted molecules or the isolated M. corti hsp70 results in the expansion of an unusual cell type with the morphology of large granular lymphocytes. The cell lines express Thy-1, CD4 (low), and CD45RB but lack TCR alpha beta, TCR gamma delta, CD3, CD8, and slg. The lack of a TCR suggested NK cells, but no cytolytic activity could be detected. In addition, the cell lines constitutively produce IL-6 and can be induced to express IL-2, but not IL-4, IL-5, or IFN gamma. Given the phenotype of these cells, it is possible that they represent T lineage precursors or some type of effector cells. Notably, CD3- CD4+ cells appear to be expanded in the spleens and livers of M. corti-infected animals, suggesting an important role in infection. Moreover, the selective growth of this cell type with M. corti hsp70 suggests that the outgrowth and in vivo expansion of these cells may be related to the stress response of the parasite. PMID- 8436821 TI - Leishmania major interferes with antigen presentation by infected macrophages. AB - Impairment of the Ag-presenting capacity of macrophages harboring intracellular Leishmania might represent one of the several mechanisms by which these parasites can evade host-protective T cell responses. Thus, the present study was designed to investigate the ability of macrophages, parasitized with Leishmania major, to present Ag to relevant T cell hybridomas. Results show that bone marrow-derived macrophages from BALB/c mice, after infection with L. major, have a greatly reduced capacity to present OVA, beta-galactosidase, and L. major-derived Ag to specific T cell hybrids derived from mice immunized with those Ag. In contrast, after pulsing with relevant peptide, macrophages containing L. major have a normal Ag-presenting capacity. The inhibition of presentation of native Ag did not appear to result from decreased endocytosis or catabolism. Inasmuch as the inhibition of presentation could not be attributed to an impaired processing of the Ag or an unavailability of MHC class II molecules on the surface of infected cells, these results could indicate that the presence of L. major interferes with the intracellular loading of MHC class II molecules with antigenic peptides. PMID- 8436822 TI - Vaccination with recombinant filarial paramyosin induces partial immunity to Brugia malayi infection in jirds. AB - Vaccination with irradiated infective larvae induces partial protective immunity to infection with the filarial nematode Brugia malayi in jirds. Prior studies have shown that such immunization stimulates a much stronger antibody response to recombinant and native filarial paramyosin than that seen after normal infection. To determine whether vaccination with recombinant paramyosin could induce protective immunity to larval challenge, jirds were immunized with either B. malayi paramyosin and maltose binding protein (BM5-MBP) (fusion protein of B. malayi paramyosin and maltose-binding protein), MBP alone, or recombinant Dirofilaria immitis paramyosin. Animals were challenged with 100 infective larvae s.c. 8 wk after the second immunization. Necropsies were performed 16 wk after challenge. Vaccination with BM5-MBP induced significant protective immunity; adult worm recoveries, worm lengths, and blood microfilaria counts were reduced in the BM5-MBP group relative to the MBP control group. The reductions in adult worm recoveries (43%) and female worm lengths (10%) were statistically significant (p < 0.05). Interestingly, protective immunity was not induced by immunization with D. immitis paramyosin. Additional studies are needed to identify mechanisms involved in protective immunity induced by BM5-MBP and to understand the differential activity of the two closely related recombinant paramyosin proteins in this model. PMID- 8436823 TI - Macrophage activation: lipoarabinomannan from avirulent and virulent strains of Mycobacterium tuberculosis differentially induces the early genes c-fos, KC, JE, and tumor necrosis factor-alpha. AB - Lipoarabinomannan (LAM) is a major cell-wall associated glycolipid produced by Mycobacterium tuberculosis and Mycobacterium leprae. Previous work demonstrated that LAM from avirulent (H37Ra) and virulent (Erdman) strains of M. tuberculosis differ in structure at their non-reducing termini. In this study the effects of the H37Ra and Erdman LAM on the activation of murine bone marrow-derived macrophages has been investigated. Their abilities to elicit immediate early gene responses at mRNA (c-fos, JE, KC) and protein (TNF-alpha secretion) levels, and nitrite production, was examined. H37Ra LAM, but not Erdman LAM, elicited TNF alpha secretion at 1000 ng/ml. Neither stimulated production of reactive nitrogen intermediates (RNI). Addition of 25 U/ml IFN-gamma enhanced TNF-alpha secretion in response to H37Ra LAM, reducing the threshold level of LAM required to 10 to 100 ng/ml. In contrast, Erdman LAM at concentrations up to 1000 ng/ml could not induce macrophage TNF-alpha secretion even in the presence of 25 U/ml IFN-gamma. H37Ra LAM also synergized with IFN-gamma to stimulate enhanced production of RNI, whereas IFN-gamma and Erdman LAM did not elicit RNI production. Examination of events before TNF-alpha and RNI production revealed that H37Ra LAM, like LPS, was able to induce increased levels of mRNA expression for c-fos, KC, and JE, with similar kinetics but reduced potency compared with LPS. Erdman LAM in concentrations up to 2500 ng/ml was unable to stimulate c-fos, KC, or JE expression. IFN-gamma at 25 U/ml was itself a potent stimulus of JE expression, and synergized with 1000 ng/ml H37Ra, and to a lesser extent, Erdman LAM for the induction of JE. In contrast, IFN-gamma inhibited H37Ra LAM stimulation of KC expression. The phenomenon of avoiding the stimulation of macrophage immediate early gene expression may be an important determinant of mycobacterial virulence. PMID- 8436824 TI - Augmentation by IL-1 alpha of tumor necrosis factor-alpha cytotoxicity in cells transfected with adenovirus E1A. AB - The introduction of adenovirus E1A into NIH3T3 mouse fibroblasts renders them susceptible to the cytotoxic action of TNF-alpha. We found that cells transfected with 13S E1A cDNA were not similarly rendered sensitive to IL-1 alpha; however, in cells transfected with 13S E1A cDNA, TNF cytotoxicity was augmented by treatment with IL-1. To understand the role of E1A in the cytotoxic action of these cytokines, several 13S E1A cDNA deletion mutants were constructed, transfected into NIH3T3 cells, and tested for their ability to induce TNF sensitivity in the presence and absence of IL-1. Cells transfected with mutants of 13S E1A with deletions of carboxyl-terminal amino acids 223 to 289 or 151 to 289 (conserved region 3) exhibited a minimal ability to reverse E1A-induced TNF cytotoxicity but a significant ability to reverse IL-1-mediated augmentation of TNF cytotoxicity. Cells transfected with other deletion mutants of 13S E1A, including those with an internal deletion encompassing conserved region 1 (amino acid positions 23 to 107) or a deletion including conserved regions 2 and 3 (amino acid positions 108 to 289), although initially TNF resistant, became TNF sensitive on prolonged exposure to TNF. Cells transfected with these mutants also showed a reduction in IL-1-augmented TNF cytotoxicity. The larger internal deletion of E1A at amino acid positions 23 to 150 (conserved regions 1 and 2), which includes regions important for transformation, transcriptional repression, and association with cellular proteins, resulted in the complete loss of the ability of E1A to induce TNF sensitivity even in the presence of IL-1. Immunoprecipitation experiments showed that E1A proteins in NIH3T3 cells associated with a cellular 115-kDa protein, which did not co-migrate with the RB gene product; the possible involvement of this protein in E1A-mediated TNF cytotoxicity is discussed. Taken together, these results indicate that conserved regions 1 and 2 are required for E1A-mediated TNF cytotoxicity. In contrast, maximal IL-1-augmented TNF cytotoxicity requires conserved region 3 as well as the nonconserved carboxyl-terminal region of the 13S E1A product. PMID- 8436825 TI - Cartilage degradation by cocultures of transformed macrophage and fibroblast cell lines. A model of metalloproteinase-mediated connective tissue degradation. AB - A number of human and mouse macrophage and fibroblast cell lines were examined for their ability to degrade cartilage proteoglycan in an attempt to establish a cell culture model of cartilage degradation. The mouse transformed macrophage cell line J774A.1 alone or in combination with the mouse transformed fibroblast cell line 10ME HD A.5R.1 were the only cell lines capable of extensively degradating cartilage proteoglycan. Incubation of the macrophage cell line J774A.1 on heat-killed cartilage disks resulted in the release of 36% +/- 8 (mean +/- SEM, n = 5) of the radiolabeled cartilage proteoglycan. The fibroblast cell line 10ME HD A.5R.1 alone did not degrade cartilage. However, cocultures of J774A.1 macrophages and 10ME HD A.5R.1 fibroblasts incubated on cartilage discs resulted in the release of 69% +/- 6 (mean +/- SEM, n = 5) of radiolabeled proteoglycan. There was little degradation of cartilage by macrophage/fibroblast cocultures during the first 3 days of culture. Cartilage degradation increased with each subsequent day in culture from 7% +/- 2 on day 4 to 68% +/- 3 (n = 3) by day 7. Supernatants from the macrophage/fibroblast cocultures were incubated with cartilage discs in the presence of general class-specific proteinase inhibitors. The metalloproteinase inhibitors 1,10 phenanthroline, EDTA, and recombinant tissue inhibitor of metalloproteinase were the only inhibitors that significantly blocked cartilage degradation by coculture supernatant. The cartilage degrading metalloproteinase in the macrophage/fibroblast coculture supernatant eluted as a broad peak on Sephacryl S-200HR with an estimated molecular mass between 22 and 55 kDa. These studies suggest that the macrophage/fibroblast coculture model of cartilage degradation may be a useful experimental system for the study of metalloproteinase-mediated connective tissue degradation. PMID- 8436826 TI - IL-4 attenuates the transcriptional activation of both IFN-alpha and IFN-gamma induced cellular gene expression in monocytes and monocytic cell lines. AB - The interaction of IFN-alpha and IFN-gamma with monocytes results in several actions that significantly influence the course of an immune response. Many of these effects are proinflammatory and can contribute to the degree of tissue injury at a site of inflammation. Whereas recent investigations target IL-4 as a T cell product that can antagonize some of the responses induced by IFN, little is known regarding the mechanisms involved. We have taken advantage of two well defined systems: the transcriptional activation of the cellular genes ISG-54 by IFN-alpha and IP-10 by IFN-gamma. IL-4 treatment of both the monocytic leukemia cell line, THP-1, and normal peripheral blood monocytes resulted in inhibition of IFN-induced RNA levels for both genes. Nuclear run-on assays in THP-1 cells indicated that the effects of IL-4 were due to the inhibition of the transcriptional activation of these genes by both IFN-alpha and IFN-gamma. This inhibition was not due to alteration in the binding characteristics of IFN-alpha or IFN-gamma to the cell. In the IFN-alpha system, we were able to show that IL-4 treatment resulted in reduced formation of the transcriptional activator, IFN stimulated gene factor 3. This reduction appears to be the result of a defect in the ability of IFN alpha to activate the IFN-stimulated gene factor 3 alpha component of IFN-stimulated gene factor 3. PMID- 8436827 TI - Lactate transport in macrophages. AB - Macrophages perform phagocytic and effector activities in a number of different tissues. The environment of the inflammatory foci in which they function is often acidic and contains an abundance of lactate. We characterized the ability of thioglycollate-elicited mouse peritoneal macrophages to accumulate lactate from the medium and to use this lactate to maintain intracellular energy stores. Lactate uptake was stereospecific for L-lactate and was inhibited by the organic anion transport blocker probenecid but not by concentrations of 4,4' diisothiocyanatostilbene-2,2'-disulfonic acid that block anion exchangers. L [14C]Lactate uptake was not affected by variation of the extracellular Na+ concentration but was enhanced by acidification of the extracellular medium, suggesting that lactate uptake was mediated by a proton cotransport system. The enhanced accumulation of [14C]-lactate seen in medium at pH 6.0 to 6.5 was inhibited by probenecid or by an excess of unlabeled L-lactate. When macrophages were incubated in PBS without glucose for 6 h, intracellular stores of phosphocreatine were 13 nmol/mg of protein, compared with 44 nmol/mg of protein in cells incubated in medium containing glucose. When lactate was substituted for glucose, phosphocreatine stores were 32 nmol/mg of protein. These studies reveal that macrophages take up L-lactate in a pH-dependent manner and that lactate uptake occurs via a probenecid-inhibitable monocarboxylate transporter; they suggest that macrophages can utilize this lactate as an energy source. PMID- 8436828 TI - Thrombospondin promotes both chemotaxis and haptotaxis in neutrophil-like HL-60 cells. AB - Differentiation of the human promyelocytic leukemia cell line HL-60 to polymorphonuclear leukocyte (PMN)-like cells with DMSO provides an important model for studying the acquisition of PMN functional responses that accompany differentiation. We showed previously that the extracellular matrix (ECM) protein thrombospondin (TSP) binds to PMN surface receptors and promotes adhesion and motility. Undifferentiated HL-60 cells did not adhere and were not motile in response to TSP, whereas cells differentiated toward PMN-like cells demonstrated both TSP-mediated adhesion and chemotaxis, with chemotaxis evident by day 2 of induction. With differentiation, a maximal response was obtained with 100 to 300 nM TSP, 10-fold lower than required for maximal PMN chemotaxis. Checkerboard analysis confirmed the directional nature of motility. mAb recognizing different domains of TSP inhibited chemotaxis, suggesting the involvement of multiple sites on TSP. Although both the NH2-terminal heparin-binding domain (HBD) and 140 kDa COOH-terminal fragment supported chemotaxis in PMN-like cells, neither fragment was as potent as intact TSP. Both pertussis and cholera toxin inhibited TSP mediated chemotaxis, suggesting the involvement of GTP-binding proteins. The toxin effects did not indirectly result from elevated cAMP levels because high concentrations of either 8-bromo-cAMP or dibutyryl cAMP did not inhibit chemotaxis. TSP bound to nitrocellulose filters induced the directed migration (haptotaxis) of PMN-like cells rather than the random motility observed with PMN. Haptotaxis was stimulated by either the HBD or 140-kDa fragment and was inhibited by mAb against these two domains. Haptotaxis rather than random migration was confirmed by checkerboard analysis. Our results demonstrate that PMN-like HL-60 cells respond differently to TSP than human peripheral blood PMN. These differences may reflect 1) an aberration in HL-60 differentiation reflecting their leukemic phenotype 2) differentiation of HL-60 cells to a cell type characteristic of "activated" PMN. PMID- 8436829 TI - Activation of tumor necrosis factor-alpha production from human neutrophils by IL 2 via IL-2-R beta. AB - In addition to T cells, NK cells, B cells, and monocytes, we provide new evidence that human polymorphonuclear neutrophils (PMN) can be functionally activated by IL-2 via binding to IL-2R beta expressed on the cell surface. Brief exposure of normal PMN to human rIL-2 enhanced both transcriptional and translational expression of TNF-alpha. The release of TNF-alpha protein by IL-2-treated PMN was inhibitable by a specific mAb against human IL-2-R beta. The response to IL-2 was dose and time dependent with the increase in TNF-alpha mRNA detected maximally 3 h after IL-2 exposure, followed by a continuous maintenance of high mRNA levels up to 18 h. The TNF-alpha mRNA was significantly increased above the medium control level, with as little as 10 U/ml of IL-2. Maximal transcription was obtained with 1000 U/ml of IL-2, which achieved the level observed with known neutrophil activating factors such as granulocyte-macrophage-CSF, IL-8, and Candida albicans. Using actinomycin D, it was found that new and continuous synthesis of a labile TNF-alpha mRNA was responsible for the observed high levels of transcripts. Of significance was the observation that cycloheximide could selectively modulate TNF-alpha mRNA transcription in neutrophils, depending on the cytokine used. Cycloheximide did not affect or alter TNF-alpha mRNA induction in IL-2-treated neutrophils but abrogated it in granulocyte-macrophage-CSF treated neutrophils and superinduced transcription in C. albicans-treated neutrophils. Thus various control elements must be involved in the transcription of the TNF-alpha genes that are responsive to different cytokines and activating factors. The induction of TNF-alpha and functional activation of neutrophils by IL-2 is therefore an important immunomodulatory property of IL-2 that has not heretofore been recognized. PMID- 8436830 TI - Glucocorticoid therapy alters hormonal and cytokine responses to endotoxin in man. AB - Previous experimental data have demonstrated that steroid pretreatment regulates endotoxin-elicited cytokine production. The timing of such hypercortisolemia also appears to be a major determinant of both the systemic and the cytokine response to infectious stimuli. Our study was undertaken to further study the in vivo influence of glucocorticoid infusion concurrent with and before endotoxin exposure in man. A total of 23 normal human subjects were given endotoxin (LPS) alone or pretreated with hydrocortisone infusion for 6 h immediately before and concomitant to LPS administration; or rendered hypercortisolemic for a 6-h period waiting 6, 12, or 144 h before LPS administration. LPS administration was followed by significant elevations in temperature (1.9 +/- 0.3 degrees C), pulse (29 +/- 6 bpm), and resting energy expenditure (26.2 +/- 0.4 kcal/kg/day) as well as epinephrine (236 +/- 59 pg/ml), cortisol (296 +/- 29), and C-reactive protein (4.2 +/- .03 mg/dl) as compared with base-line values. Levels of TNF and IL-6 that were not detectable before LPS administration, peaked, respectively, at 90 and 120 min after LPS (155 +/- 4 pg/ml, 12 +/- 1 U/ml). Glucocorticoids when given immediately before and concomitant with LPS significantly attenuated the temperature (0.8 +/- 0.01 degrees C) and pulse rate response (10 +/- 3 bpm) seen after LPS alone as well as suppressing peak levels of epinephrine (78 +/- 14 pg/ml) and C-reactive protein (undetected). TNF remained undetectable in this group although the IL-6 response (14 +/- 1 U/ml) was unchanged. With a 6-h interval between hydrocortisone infusion and LPS challenge, changes in temperature, pulse, resting energy expenditure, and hormone levels were similar to those seen after LPS alone whereas TNF remained undetectable and IL-6 levels were similar to subjects receiving LPS alone. Subjects receiving LPS after 12 or 144 h after hydrocortisone infusion displayed hemodynamic and hormonal responses similar to the LPS alone group, yet mounted significantly greater circulating levels of both IL-6 (117 +/- 14 U/ml, 160 +/- 51 U/ml at 12 and 144 h) and TNF (609 +/- 173, 671 +/- 132 pg/ml at 12 and 144 h) to those observed after LPS alone. We conclude that antecedent periods of hypercortisolemia participate in regulation of the hemodynamic, hormonal, and cytokine responses to endotoxin and that a complex temporal relationship between hypercortisolemia and LPS induced cytokine and systemic responses exists. PMID- 8436831 TI - Influence of nephrectomy on tumor necrosis factor clearance in a murine model. AB - TNF, a cytokine with multiple properties, is known to be rapidly inactivated in vivo. In patients with septic shock and kidney malfunction, conflicting data have been reported regarding the presence of TNF in the circulation. Recently, we have shown that these differences can be the result of the detection of free TNF vs TNF complexed with soluble TNF-R. Enhanced levels of soluble TNF-R have been reported in patients with kidney malfunction. Because the kidney is thought to play an important role in TNF and TNF-R metabolism, we investigated the influence of bilateral nephrectomy on TNF clearance and TNF-R regulation in a murine model. The data obtained show that bilateral nephrectomy results in circulating levels of immunologically detectable (ELISA), but not biologically active (bioassay), TNF. Injection of endotoxin results in significantly higher levels of immunologically detectable TNF in bilaterally nephrectomized mice, compared with sham-operated mice, whereas biologically active levels were similar. To investigate the roles of TNF-R1 (P55) and TNF-R2 (P75) in this process, clearance of TNF was studied by injection of murine and human TNF. Murine TNF injection leads to comparable clearance of bioactive TNF in nephrectomized and sham operated mice (t1/2 = approximately 12 min). However, clearance of immunologically detectable murine TNF is significantly slower in nephrectomized mice, compared with sham-operated mice (t1/2 = 96 min vs 26 min, respectively; p < 0.05). Administration of human TNF results in a significantly lower clearance in nephrectomized mice, compared with sham-operated mice (t1/2 = 108 min vs 25 min, respectively; p < 0.05). This is observed for both bioactive human TNF and immunologically detectable human TNF. Based on the fact that murine TNF-R1 (55 kDa) has a similar affinity for murine and human TNF, whereas murine TNF-R2 (75 kDa) shows affinity only for murine TNF, the data obtained suggest an important role for TNF-R2 in inactivation and clearance of TNF by the kidney. Moreover, the data suggest that kidney malfunction affects TNF clearance, leading to increased amounts of circulating TNF-TNF-R complexes, which could function as a slow release reservoir for TNF. PMID- 8436833 TI - Differential usage of T cell receptor V gene segments in CD4+ and CD8+ subsets of T lymphocytes in monozygotic twins. AB - The TCR confers immunity by the specific recognition of foreign Ag peptides in the context of self-MHC molecules. The mechanisms controlling TCR selection and repertoire generation are not clearly understood and seem to occur in an apparently random, (self) Ag-driven manner. To address the question to what extent the TCR repertoire is randomly shaped or genetically predetermined, we have analyzed the alpha beta TCR repertoire of the CD4+ and CD8+ subsets of peripheral blood lymphocyte cultures of monozygotic twins by using the polymerase chain reaction technique with TCR V region gene family-specific oligonucleotide primers. Our studies demonstrate that there is high concordance in the overall patterns of V gene usage within a pair of twins, particularly in V beta usage (mean V beta CD4+ R2 = 0.869 and CD8+ R2 = 0.833) and to a lesser extent V alpha usage (mean V alpha CD4+ R2 = 0.621 and CD8+ R2 = 0.627); whereas the patterns between unrelated individuals show more variability. This study has also demonstrated that the V alpha and V beta genes are not randomly used within the CD4+ and CD8+ subsets. We observed significant preferential skewing of several V alpha or V beta gene families to either the CD4+ or CD8+ subset in the majority of individuals analyzed (p-value range = 0.0476 to < 0.001). In particular, V alpha 11, 17, 22, and V beta 3, 9, 12, 18 were skewed to the CD4+ subset; whereas V alpha 2, 6, 12, 15, 20 and V beta 7, 14, 17 were skewed to the CD8+ subset. Furthermore, a number of the V genes showed patterns of skewing consistent only within a pair of twins. In three pairs of twins, V beta 2 was skewed to the CD4+ subset, whereas the fourth pair used almost equal frequencies of V beta 2 in both subsets. This observation was made for the V beta 2, 4, 5, 6, 8, 19 and V alpha 7, 16, 18, 21 families. Finally, the ratio of the relative V gene usage frequency that could be observed within an individual was conserved within the sets of twins; for instance, the relative amount of V beta 2 to that of V beta 3 was higher in both individuals of one set of twins, whereas it was lower in all of the other three sets. Together these observations suggest that the predominant influence shaping the TCR repertoire is genetically predetermined, of which, HLA predicted selection mechanisms exerted during thymic maturation might be contributing factors. PMID- 8436832 TI - Autoantibodies directed against different classes of Fc gamma R are found in sera of autoimmune patients. AB - Serum samples from 147 patients with different systemic autoimmune diseases (SLE, Sjogren's syndrome, and progressive systemic sclerosis) were tested for anti-Fc gamma R activity using mouse rFc gamma RII in an ELISA. High reactivity compared to normal individuals was found for patients with all three diseases. The anti-Fc gamma R antibody was purified from several serum samples by affinity chromatography on a Sepharose column coupled with denatured, murine rFc gamma RII. Both IgM and IgG antibodies were found. To analyze the specificity of the affinity-purified autoantibody, cells (human neutrophils, IFN-gamma-stimulated neutrophils, monocytes, and the THP-1 monocytic cell line) that express different combinations of Fc gamma R (CD64, CD32, CD16) were stained with the affinity purified Ig. Ig directed against all three types of Fc gamma R were found. The results may reflect on the role of Fc gamma R-specific antibodies in the pathology of autoimmune diseases. PMID- 8436834 TI - Age-dependent V region expression in the human antibody response to the Haemophilus influenzae type b polysaccharide. AB - The human L chain antibody repertoire specific for the Haemophilus influenzae type b (Hib) polysaccharide (PS) is composed of kappa I, kappa II, kappa III, kappa IV, and lambda L chain V regions, but the most commonly occurring VL is encoded by the unmutated V kappa II-A2 gene. To determine whether this VL repertoire is influenced by age, we used idiotypic probes to monitor V kappa II A2, V lambda, and V kappa III usage in the antibody response to an Hib PS-protein conjugate vaccine. A single dose of a vaccine consisting of Hib PS coupled to an outer membrane protein complex of Neisseria meningitidis was administered. Adults (n = 35), 18-month-old infants (n = 35), and 2-month-old infants (n = 46), all with > or = 0.9 microgram/ml anti-Hib PS antibodies, were tested for VL region markers in postvaccination sera. V kappa III anti-Hib PS antibodies were not detected in any of the 2-month-old infants but were detected in 29% of the 18 month-old infants and 69% of the adults (p < 0.001). The lack of kappa III antibodies in 2-month-old infants could not be accounted for by lack of a kappa response, because kappa antibodies to Hib PS were present (> 0.15 microgram/ml) in 45% of these infants. Hibld-1, an idiotope expressed by anti-Hib PS antibodies having the kappa II-A2 V region, was present in postvaccination sera of 66% of the adults and 80% of the 18-month-old infants but was less frequent in the 2 month-old infants (35%, p < 0.001). In contrast, Hibld-2, which is an idiotope expressed by a subset of V lambda VII anti-Hib PS antibodies, was rare or infrequent in adults and 18-month-old infants (0% and 6%, respectively) but was present in 43% of 2-month-old infants (p < 0.001). Our findings demonstrate that dramatic changes in VL region utilization occur in the human antibody response to this Hib PS conjugate vaccine as a function of age. Because previous studies have shown that V region usage correlates with antibody fine specificity and avidity for Hib PS, these age-related differences in V region expression may affect the ability of vaccines to confer protective immunity at different ages. PMID- 8436835 TI - Antigens of varying size persist longer in subepithelial than in subendothelial immune deposits in murine glomeruli. AB - The kinetics of removal of immune deposits from the subendothelial and subepithelial areas of glomeruli were analyzed in mice. Radiolabeled, cationized Ag of different molecular size, including human serum albumin, bovine thyroglobulin, and human IgM, were used to form the immune deposits in mouse glomeruli with specific, purified rabbit antibodies to these proteins. The disappearance curves of the radiolabeled Ag from glomeruli consisted of two exponential components. The immune deposits and their location in glomeruli were identified by immunofluorescence and electron microscopy. The t1/2 of disappearance of immune deposits were assigned to subendothelial or subepithelial deposits on the basis of ultrastructural observations. The t1/2 of subendothelial immune deposits ranged from 0.6 to 1.9 days with the three different Ag-antibody systems. In contrast, the t1/2 of the subepithelial immune deposits ranged from 9.32 to 231 days. The cationized human serum albumin in subepithelial areas had the longest t1/2, and this was not altered by the endogenous immune response to the injected materials, as determined in studies with nude mice. The results constitute formal documentation of the prolonged t1/2 of an exogenous Ag in glomerular immune deposits. The described approach can serve to examine variables that alter this prolonged presence of subepithelial immune deposits in glomeruli. PMID- 8436836 TI - Complete Freund's adjuvant-induced T cells prevent the development and adoptive transfer of diabetes in nonobese diabetic mice. AB - Insulin-dependent diabetes mellitus is an autoimmune disease that is characterized by the destruction of insulin-producing beta cells in the islet of Langerhans. We have recently reported that the induction of the disease in nonobese diabetic (NOD) mice can be prevented by a single injection of CFA. In this study, we have explored the cellular basis and the time course of the disease protection. Since CFA contains a mycobacterial cell wall that has adjuvant property, we investigated the protective role of mycobacteria in young NOD mice. Mice injected with Mycobacterium tuberculosis or Mycobacterium bovis (BCG vaccine) at 4 wk of age were also found to be protected from diabetes. We have found that complete protection from diabetes is only achieved by administration of CFA between 4 and 10 wk of age. Draining lymph node cells or spleen cells from CFA-treated NOD mice transfer the protection. Adoptive transfer of spleen cells from CFA-treated mice with spleen cells from acutely diabetic mice delayed the induction of disease into irradiated recipient mice. CFA-treated old NOD mice were also resistant to passive transfer of disease by spleen cells from acutely diabetic mice. Depletion of the Thy 1.2+ cells or CD4(+)-bearing T cells abrogated the protection. However, disease can be induced in the protected mice by cyclophosphamide treatment. We also found that thymocytes from NOD mice responded only weakly to mitogen Con A. CFA treatment, however, restored the ability of these cells to respond to Con A. Finally, our results suggest that T cells induced after CFA treatment of NOD mice prevent both the induction and effector phases of the disease. PMID- 8436837 TI - [Experimental study on cause of pulmonary hypoplasia in the rabbit fetus]. AB - To study the role of thoractic compression in the etiology of pulmonary hypoplasia associated with oligohydramnios, we shunted amniotic fluid into the maternal abdominal cavity at day 24 of gestation (canalicular phase) in one group of fetal rabbits. This procedure produced oligohydramnios and newborns undergoing this procedure had a significantly decreased lung/body weight (LW/BW) ratio at reexploration on day 29. To determine the morphometry of fetal rabbit lung growth, we quantitated the size of lung acinus, the number of terminal airspaces generated terminal airspaces and the diameter of the alveoli was significantly decreased in shunted rabbit fetuses. To examine the influence of the timing and duration of oligohydramnios, we shunted at 22, 24, 26 and 28 days of gestation. The LW/BW ratio and the number of terminal airspaces generated significantly decreased in shunted fetuses on days 22 and 24. To inhibit the loss of fetal lung fluid in oligohydramnios, tracheal ligation (TL) and aminotic fluid shunt (AS) was performed at day 24 of gestation. The TL combined with AS group had the same LW/BW ratio and the number of terminal airspaces generated as the control. We conclude that oligohydramnios induced lung hypoplasia and the degree of lung hypoplasia depends on the time of onset and duration of oligohydramnios, and that lung hypoplasia associated with oligohydramnios is related to the loss of lung fluid. PMID- 8436838 TI - [Relationship between polyunsaturated fatty acid (PUFA) and learning ability in the brain of rat fetus and newborn]. AB - We prepared rat newborns deficient in omega 3-polyunsaturated fatty acid (SA group) and studied the relationship between the fatty acid composition of the brain and the learning ability. DHA in the brain was decreased and the conditioned avoidance rate was lower in the SA than in the control group (SO group). In the SAO-1 group in which PUFA deficient diet was changed to the control diet on weaning (21 days after birth) and the SAO-2 group in which the diet PUFA deficient diet was changed to the control diet at the start of the Shuttle Box (60 days after birth), the conditioned avoidance rate increased later than in the SO group. After completion of the experiment the levels of, DHA, C22:5 omega 6 in the SAO-1 and SAO-2 groups recovered to the level of the SO group. Accordingly, it is suggested that the fatty acid composition of the brain is affected by the diet and that the learning ability is altered in parallel with the composition of the DHA. These findings confirm the importance of DHA as a constituent element of the brain. PMID- 8436839 TI - [Epidermal growth factor regulates trophoblast proliferation and differentiation in an autocrine/paracrine manner]. AB - Effects of epidermal growth factor (EGF) on the expression of trophoblast proliferation and differentiation were investigated in vitro using an organ culture system of human placental tissues. Explants of trophoblastic tissues obtained from each trimester of gestation were cultured with or without EGF (100 ng/ml) in serum-free conditions. In order to determine the possible effect of EGF on the proliferation activity of villous trophoblasts, immunostaining with monoclonal antibody Ki-67 was used. On the other hand, the possible effect of EGF on the differentiated cellular function of villous trophoblasts was assessed by determining the ability to secrete hCG and hPL. In 4-5 week placenta, EGF and EGF receptor were found to be almost exclusively localized in cytotrophoblasts and EGF enhanced the proliferation of cytotrophoblasts without affecting the ability to secrete hCG and hPL, whereas in 6-12 week placenta, EGF and EGF receptor were predominantly localized in syncytiotrophoblasts and EGF stimulated the secretion of hCG and hPL without affecting the proliferation of cytotrophoblasts. These findings suggest that EGF has dual actions which independently affect trophoblast proliferation and differentiation in the first trimester of gestation in an autocrine manner. But, in the second and third trimesters of gestation, EGF mediates the expression of placental function in a paracrine manner. PMID- 8436840 TI - [Studies on pharmacokinetics of platinum after internal iliac artery infusion of cisplatin in rabbits]. AB - The purpose of this study was to evaluate the usefulness of internal iliac artery infusion chemotherapy with cisplatin (CDDP) for uterine cancer. The rabbit model for internal iliac artery infusion was designed and then induced. The rabbits (average BW 3.5kg) were treated with CDDP (1.7mg/kg) via either the internal iliac artery (IA) or peripheral vein (IV) as the control. The rabbits were infused with CDDP via the IA for 2 minutes, 20 minutes or 2 hours, or via IV for 2 minutes or 20 minutes. Platinum (Pt) concentrations were measured in the serum and tissues of the uterus and kidney after CDDP infusion. Concentrations of filtrated Pt in serum were significantly lower and concentrations of Pt in uterine tissue were significantly higher after IA infusion. The highest concentration of Pt in uterine tissue was obtained after 20 minutes of IA infusion. However, the uterine Pt concentration after IA infusion for 2 hours did not differ from that after IV infusion. A significant amount of Pt was also retained in kidney tissue after IA infusion, which was not different from that after IV infusion. These findings with the rabbit model suggest that IA infusion of CDDP for 20 minutes is useful in treating uterine cancer. PMID- 8436841 TI - [A case of fetal hydrocephalus with intracranial hemorrhage after maternal hypovolemic shock]. PMID- 8436842 TI - [A study on relation between fecundability and infertility factors after laparoscopy]. PMID- 8436843 TI - [The bone mineral density change with aging of women and usefulness of single energy X-ray absorptiometry for measurement of bone mineral content]. AB - The calcaneus bone mineral density of 473 women was measured by single photon absorptiometry (SPA) and the vertebrae bone mineral density of 198 women was measured by dual energy X-ray absorptiometry (DEXA). The calcaneus bone mineral density of women starts decreasing at age 30, and the rate of decrease accelerates after the age of 50. The vertebrae bone mineral density starts decreasing at the age of 35, and a conspicuous decrease can be seen after the age of 50 as well. Because bone deterioration of Japanese women is thought to start earlier than in Europeans and Americans, the necessity of osteoporosis screening before menopause was suggested. A high positive correlation (r = 0.804) between calcaneus bone mineral density and vertebrae bone mineral density was found, and a high degree of precision of SXA was shown. PMID- 8436845 TI - Post-traumatic neuralgia in the upper extremity treated with extraneural scar excision and flap cover. AB - 19 patients with neuralgia in the upper limb after surgical or non-surgical trauma to peripheral nerves were treated by excision of the extraneural scar and surrounding hypersensitive skin and application of free or pedicle flaps. The subcutaneous fat of the flaps was wrapped around the affected nerves. After a mean follow-up time of 5.8 years the patients were sent a questionnaire. Only one patient considered herself cured, six were almost cured and seven improved. Two patients were unchanged and three worse. The results after three to four months appeared stable. PMID- 8436844 TI - Premature closure of the distal radial physis. AB - Two cases of fracture of the radius treated by pinning resulted in severe wrist joint deformity due to premature closure of the epiphysial growth plate. Inappropriate pinning through the physis damaged the growth plate in both cases. They were treated by bone bridge resection with free fat interposition. The bone bar resection was effective in correcting the wrist joint deformity, and bone growth was expected without bone grafting. PMID- 8436846 TI - Hand infections: an audit of 160 infections treated in an accident and emergency department. AB - 160 consecutive hand infections presented to an Accident and Emergency department over a four-month period. All but one were treated solely on an out-patient basis. The mean delay to presentation was three days, the mean duration of treatment was six days. Follow-up to complete resolution was achieved in 89% of cases. No patients were treated with parenteral antibiotics. The need for careful assessment, early aggressive surgery, and meticulous attention to the principles of wound care by experienced clinicians is emphasized. PMID- 8436848 TI - Injuries to the hand in rugby union football. AB - Hand injuries are a common consequence of playing rugby. A prospective study of all rugby injuries referred to a hand clinic over the course of one season was carried out. 72 patients with such injuries were seen. There were 46 fractures and 26 soft tissue injuries. A substantial number were caused deliberately by opponents. One-third of the injuries were thought to be preventable. PMID- 8436847 TI - Bilateral pyoderma gangrenosum of the hand: treatment with dapsone. AB - The first reported case of bilateral pyoderma gangrenosum of the hands is presented. One lesion was treated with wound care only, with spontaneous healing after two months. The contralateral lesion which occurred one month later was treated with wound care and oral dapsone. Healing occurred between four and six weeks after the start of dapsone. It is suggested that this acts by limiting the necrotizing process, thus allowing earlier epithelialization. Pyoderma gangrenosum is rare, and treatment is non-surgical. It is important that it is recognized to avoid extension of the necrotizing process through ill-advised surgery. PMID- 8436849 TI - Hand function after digital amputation. AB - 127 patients with amputated thumbs or fingers between the level of the DIP and MP joints were followed up at regular intervals until one year after injury. Sensory disturbances subsided rapidly except for numbness which was still present in 50% at one year. Range of movement was regained early. Although pronation and supination improved to 70% only a few months after injury, it took a year for power grip and key pinch to regain 70%. Further analysis showed that power grip was worst in amputees of multiple fingers, thumb, and the middle finger through the proximal phalanx. For key pinch, almost all were impaired to a level of 50% to 60%. Multiple finger amputees also had decreased pronation, and thumb amputees had decreased supination. Other factors were not significant. One-quarter had to change their jobs and one-fifth showed concern with the appearance. PMID- 8436850 TI - Grip strength and hand position of the dynamometer in 204 Finnish adults. AB - A primary purpose of this study was to establish data on hand strength by Jamar dynamometer for normal Finnish adults aged 30 to 50 years. A second aim was to find out how five various breadths of grip affect the strength value. A sample of 103 male and 101 female adults, aged 19 to 62, from the southern part of Finland were tested using standardized positioning and instructions. Male and female subjects reached the highest grip strength using the third handle breadth of dynamometer, except females over 50 years. Female grip strength was 60% to 70% less than male grip strength. There was no significant difference in strength between dominant and non-dominant hands. PMID- 8436851 TI - Surgical treatment of ulnar nerve entrapment at the elbow. PMID- 8436852 TI - Resection of vascular malformations. AB - A retrospective study was undertaken of 15 cases of congenital vascular malformations of the upper limb with a mean follow-up of 5.6 years. Malformations were classified on the basis of tissue involvement into local and diffuse types and the outcome of a radical surgical approach was assessed. There were seven cases of recurrence (47%). Recurrence was more frequent in the diffuse type and when excision was considered incomplete. PMID- 8436853 TI - Strength and functional recovery following repair of flexor digitorum superficialis in zone 2. AB - A two-pronged study was designed to evaluate the strength in vitro and functional recovery in vivo of FDS repairs in zone 2. In part I, horizontal mattress or Tajima grasping repairs were performed on fresh-frozen cadaveric digits, using 3/0 or 4/0 braided nylon suture material. The Tajima repair was significantly stronger than the mattress suture, using either 3/0 (P = 0.0001) or 4/0 (P = 0.0027) suture material. The 3/0 Tajima repair appeared strong enough to permit gentle early active motion. Furthermore, the clinical portion of the study (part II) demonstrated restoration of FDS function following repair in relatively isolated injuries in 13 out of 15 digits (86.7%), with PIP flexion averaging 80 degrees and grip strength 89% of that in the uninjured hand. PMID- 8436854 TI - Improved results in zone 2 flexor tendon injuries with a modified technique of immediate controlled mobilization. AB - The results following primary and delayed primary repair in zone 2 flexor tendon injuries were evaluated in 85 fingers of 79 patients using immediate controlled mobilization post-operatively. In 31 patients a conventional Kleinert technique was used. In the remaining 48 patients a modified technique was used with rubber band traction to all fingers instead of only to the injured one. Also a shorter dorsal splint was used in order to secure extension of the PIP and DIP joints. The results were improved and the time of treatment was reduced. PMID- 8436855 TI - Polydactyly of the thumb. PMID- 8436856 TI - Autogenous free sheath grafts in reconstruction of injured digital flexor tendon sheath at the delayed primary stage. AB - We report our clinical experience of reconstruction of the digital flexor sheath with free autogenous sheath graft at the delayed primary stage. In 21 digits with flexor tendon lacerations, free autogenous sheath was taken from the sheath covering the first dorsal compartment to reconstruct the digital flexor sheath, where there was an obvious defect due to trauma, contusion of the synovial surface or contracture of the digital sheath. Follow-up revealed excellent and good results in 85.7% of the cases. Ample gliding space should be kept inside the sheath tunnel to maintain tendon gliding function. PMID- 8436857 TI - The use of skin hooks and hypodermic needles in tendon surgery. PMID- 8436858 TI - A post-operative regime after digital flexor tenolysis. A series of 72 patients. AB - Tenolysis of the flexor tendons was performed in 78 fingers (72 patients) by the same surgeon. Two technical modifications were introduced: reconstruction of a robust pulley; and initial immobilization with the tendon in a proximally migrated position, permitting later breakdown of early adhesions by gentle extension either by the surgeon or using an extension spring. After a mean follow up of 21.5 months, the total active movement was improved from 135 degrees (pre operative) to 203 degrees (post-operative) in 84% of fingers and from 65 degrees to 115 degrees in 78% of thumbs. This corresponds to a reduction in impairment of 10.1% for the thumb and 21.6% for the fingers. There was no improvement in four digits and nine cases were made worse, averaging a loss of range of 25.4 degrees. Among these were two cases of skin breakdown and two cases of tendon rupture (2.5%), one combined with skin necrosis. PMID- 8436859 TI - Spontaneous compartment syndrome in a patient on long-term anticoagulation. AB - The case is reported of a 35-year-old lady on long-term anticoagulation with warfarin who developed a spontaneous acute compartment syndrome in the forearm. Despite a delay in diagnosis, an extensive decompression resulted in complete recovery. PMID- 8436860 TI - Skyline view of the metacarpal head in the assessment of human fight-bite injuries. AB - With the fingers extended, the severity of the bony injury from human fight-bite injuries can be underestimated or missed. We describe a "skyline view" of the metacarpal head highlight the intra-articular damage that can occur. PMID- 8436861 TI - Fractures of the distal end of the radius in young adults: a 30-year follow-up. AB - 76 patients were examined clinically and radiologically 27 to 36 years after a fracture of the distal radius. The average age was 31 years at the time of injury and 63 years at follow-up. In 81% of the patients there was no difference between the fractured and the non-fractured side. No patient had to change his or her occupation or leisure activities because of the fracture. There were more degenerative changes in the fractured wrist than in the non-injured side. A statistically significant correlation was found between axial compression and the presence of degenerative changes in the radio-carpal and distal radio-ulnar joints. Treatment of the fracture of the distal end of the radius in the young adult should aim to conserve the length of the radius. However, after 30 years, complaints are few and correlate with degenerative changes in the radio-carpal joint only. 47 patients with articular fractures of the distal end of the radius were examined in the same way. The average age at the time of injury was 32 years and 58% of the patients were men. In 87% of the patients there was no difference between the fractured and the non-fractured side. However 37% had minor complaints. A higher proportion of patients with articular fractures developed degenerative changes than those with non-articular fractures. The existence of radiographic signs of osteoarthritis is directly related to axial compression and the persistent incongruity, after reposition, in either the radio-carpal or the distal radio-ulnar joints. PMID- 8436862 TI - Treatment of residual instability and extensor lag in polydactyly of the thumb. AB - Extensor indicis tendon transfers were used in six cases with residual deformity of the thumb in polydactyly. The indication was extensor lag and instability of the interphalangeal joint. At mean follow-up of three and a half years, normal stability was improved. Full extension was achieved in three cases and two cases also derived some benefits from this operation. Alignment was improved in five cases. PMID- 8436863 TI - Radiological measurement of radial shortening in Colles' fracture. AB - 100 consecutive patients with Colles' fracture were assessed functionally three months after the injury, and the result correlated with initial shortening of the radius. Three methods were used to measure radial shortening; only the one that measured the distance from distal radial to distal ulnar surfaces correlated with functional outcome. It is concluded that this is the most valid method of measurement and the deficiencies of the other methods are discussed. PMID- 8436864 TI - An unusual variety of scapho-capitate syndrome. AB - We report a patient who sustained a displaced fracture of the lunate in association with fractures of the scaphoid and capitate. Union of the scaphoid and capitate fractures followed fixation with Herbert screws, 25 additional cases from the literature have been reviewed. PMID- 8436865 TI - Dorsal avulsion fractures of the scaphoid: diagnostic implications and applied anatomy. AB - Three cases of acute dorsal avulsion fracture of the scaphoid are presented. Anatomical and radiological studies indicate that these fractures arise from a ridge on the dorsum of the scaphoid at the distal end of the radial facet. This is not the site suggested by other authors. The clinical significance of these fractures is that they are only visible on the 45 degrees anteroposterior oblique X-ray view of the scaphoid. Without this view they are indistinguishable from X ray negative scaphoid fractures, since both have similar clinical signs and isotope bone scans. PMID- 8436866 TI - Rotary subluxation of the scaphoid: a spectrum of instability. AB - Rotary subluxation of the scaphoid is not an "all or nothing" phenomenon, but a spectrum of instability including constant displacement of the scaphoid apparent on plain non-stress radiographs (the previously defined static type), subluxation seen only on loading X-rays or other special studies ("dynamic"), and instability demonstrable on physical examination but not by radiographic studies ("predynamic"). A clinical study of 1,000 random individuals was carried out to determine the incidence of unilateral hypermobility of the scaphoid. 21% of the subjects were found to have an abnormal difference in mobility between their scaphoids. The incidence of significant symptoms and physical findings associated with this hypermobility was determined. PMID- 8436867 TI - The distal ligamentous complex of the scaphoid and the scapho-lunate ligament. An anatomic, histological and biomechanical study. AB - 22 fresh cadaver specimens have been examined to study the anatomy, histology and biomechanical features of the ligaments of the proximal and distal poles of the scaphoid. The biomechanical study was carried out by two methods: an analytical one on an Instron machine, and a global one in situ. The different experiments show the predominant role of the distal ligamentous complex of the scaphoid over the scapho-lunate ligament. This contrasts with the generally accepted concept and modifies the management of lateral carpal instability. PMID- 8436868 TI - Anatomical risk factors for Kienbock's disease. AB - Contralateral unaffected wrists from 41 males with Kienbock's disease were compared with wrists from 66 normal males. From X-rays, various features of the lunate and radius were measured. In patients with Kienbock's disease, the lunate tended to be smaller and inclined more radially than in normal subjects and the radial inclination was flatter. Discriminant analysis showed that 85% of the unaffected contralateral wrists in patients with Kienbock's disease and 74% of the wrists in normal subjects were accurately discriminated to their respective groups. It may be possible to identify subjects who are at risk for Kienbock's disease prior to onset using discriminant analysis. PMID- 8436869 TI - Olecranon spur. AB - Full extension of the elbow is normally made possible by accommodation of the olecranon within an appropriately shaped fossa in the distal humerus. We report three cases where disability has resulted from an abnormally shaped olecranon. PMID- 8436870 TI - Arthroscopic synovectomy of the rheumatoid wrist. AB - 18 wrists in 16 patients with synovitis due to rheumatoid arthritis were treated with arthroscopic synovectomy. The surgical procedure and the results after surgery are described. Range of motion, grip strength, subjective experience of pain and level of activity were registered pre- and post-operatively. The operations were found to give good pain relief, increased grip strength, no post operative stiffness and a short period of rehabilitation. PMID- 8436871 TI - An analysis of the results of late reconstruction of 132 median nerves. AB - 132 patients with injuries to the median nerve were assessed on average 10.4 years after repair. There were 106 males and 26 females, with a mean age of 28.4 years. Most of the nerve lesions were sharp (76) or blunt (47) injuries. Division was total in 87 cases, and most were at the wrist level. Secondary repair was performed in 34 cases and fascicular grafting in 98 cases. The average gap was 5.8 cm. A quantitative evaluation and grading according to the MRC classification was created to reflect sensory and motor recovery. Excellent or good results were obtained in only 49.2%. The age of the patient, the width of contusion, the pre operative delay, the length of grafting and the level of the injury influenced the results significantly. The result of nerve repair was poor in patients aged over 54 years, when the level of the injury was more than 56 cm proximal to the finger tip, if the pre-operative delay was more than 24 months, or if the graft length was more than 70 mm. PMID- 8436872 TI - Tube cecostomy for obstructing cancer of the left colon. PMID- 8436873 TI - The value and limitation of pleural fluid pH measurement. AB - Analysis of an aliquot of fluid from a pleural effusion will often provide the clinician with the information needed to establish a presumptive or definitive diagnosis of the patient's illness. A properly performed pleural fluid pH can maximize the diagnostic yield and provide guidelines for further clinical interventions. PMID- 8436874 TI - Cutis marmorata telangiectatica congenita. AB - Cutis marmorata telangiectatica congenita (CMTC) is an uncommon benign condition presenting at birth with levido reticularis, telangiectasia, phlebectasia, and possible ulceration of the involved skin. Diagnosis is made through the clinical picture and supported by characteristic histopathologic changes when present. This condition should not be confused with manifestations of serious system disease and aggressive treatment is not indicated. We describe in this report a case of CMTC. PMID- 8436875 TI - Men are not cost effective. PMID- 8436876 TI - A call for nutritional training. PMID- 8436877 TI - Prohibition revisited: county alcohol control consequences. AB - This study examined measures of alcohol abuse consequences in wet vs dry counties in Kentucky. Data were gathered from all counties of the state for the year 1988. Dry counties had less alcohol-related auto accidents and DUI arrests. Other alcohol-related variables, such as cirrhosis mortality, were not significantly different between wet and dry counties. When demographic variables were also considered, it was determined that the advantage enjoyed by dry counties remained. Findings indicate that county-level alcohol prohibition is effective in promoting the public's health, by improving highway safety. PMID- 8436878 TI - The 1990/91 Kentucky hospital smoking policy survey: a follow-up. AB - We surveyed all Kentucky hospitals regarding smoking policies iin 1989, 1990, and 1991. There were statistically significant increases in the numbers of hospitals which developed smoking policies and became smoke free between 1990 and 1991. The sale of tobacco in hospitals declined significantly between 1989 and 1991, as did the number of institutions providing smoking areas within the hospital. Survey respondents indicated that the JCAHO mandate prompted changes in smoking policies. Kentucky hospitals are leading the way in developing smoke-free environments, but externally imposed regulations have played a major role in promoting this progress. PMID- 8436879 TI - Primary thrombosis in the upper extremity. AB - Deep vein thrombosis may occur in the axillary or subclavian veins in the upper extremities, sometimes in young patients without the typical risk factors for thrombus development. This unusual clinical situation usually follows strenuous activity and is often referred to as "effort" thrombosis. Since some cases have occurred with mild exertion and there is a lack of obvious predisposing vessel trauma, a more correct term might be "primary" thrombosis. Early recognition of this condition is necessary to prevent potentially fatal acute effects and minimize chronic sequelae. PMID- 8436880 TI - The pulmonary autograft for aortic valve replacement in the young. AB - Until recently, a mechanical prosthesis has been the substitute valve of choice for children and young adults who require aortic valve replacement. The preference for using mechanical valves in this group resulted from the discovery that porcine valves experienced accelerated structural degeneration in the young. Unfortunately, mechanical valves impose a constant risk of thromboembolism, resulting in a lifelong requirement for anticoagulant therapy. Thus, young patients with the potential for longer survival face a higher likelihood of having a thromboembolic or hemorrhagic event. To provide young patients with a durable replacement aortic valve that is not thrombogenic and does not require anticoagulation, some cardiac surgeons are transferring the patient's own pulmonary valve to the aortic position and replacing the pulmonary valve with a cryopreserved valve (a homograft) from a cadaveric donor. Long-term follow-up of the experience of Mr Donald Ross of London, England, who introduced this operation in 1967, indicates that the pulmonary autograft has the best event-free survival of any form of aortic valve replacement. The technical demands of this operation are greater than those for routine aortic valve replacement with a mechanical prosthesis; however, the pulmonary autograft can be performed at an acceptably low risk. As more experience is acquired with this technique, it may become the preferred procedure for aortic valve replacement in the young. PMID- 8436881 TI - Maternal mortality report. PMID- 8436883 TI - Clinton's administration proposal for some aspects of health care reform. PMID- 8436882 TI - Like munching on a porcupine quill by quill. PMID- 8436884 TI - Uptake of preventive health care among Mediterranean migrants in Belgium. AB - STUDY OBJECTIVE: The aim was to investigate the influence of ethnicity on the demand for preventive care by Mediterranean migrants in Belgium. DESIGN: This was a survey of patient contacts with general practitioners. SETTING AND PATIENTS: 33 general practitioners working in Belgian localities with the highest migrant density collaborated in the study. During two months they recorded information on consultations with an estimated 72,600 clients. Participation was obtained from all subjects attending for preventive care or for a new episode of illness (n = 6256). MAIN RESULTS: An average of 30% of the patients sought preventive care, but multivariate analysis showed ethnicity to be a strong independent predictor of this type of demand. The higher primary preventive uptake by female Moroccans and Turks and the higher secondary preventive uptake by males from the same ethnic groups, as compared with the Belgian reference population, contrasted with a lower demand for tertiary prevention in migrants of either gender. The relative demand for preventive care by the more acculturated migrants was, however, quite similar to the demand of the Belgian population. CONCLUSIONS: The differential uptake of primary preventive care could be partly explained by the higher fertility rates of immigrant women, and the differential secondary uptake by a lower incidence of tuberculosis in the indigenous population. The meagre demand for tertiary prevention by Moroccan and Turkish migrants could be due to weaker compliance with treatments for chronic disorders, which is related to the perceptions of illness in these ethnic groups. The establishment of cross cultural mechanisms of dialogue should enhance compliance and improve the access of immigrants to the benefits of tertiary preventive care. PMID- 8436885 TI - Health and re-employment in a two year follow up of long term unemployed. AB - STUDY OBJECTIVE: The aim was to examine re-employment and changes in health during a two year follow up of a representative sample of long term unemployed. DESIGN: This was a cross sectional study and a two year follow up. Health was measured by psychometric testing, Hopkins symptom checklist, General health questionnaire, and medical examination. Health related selection to continuous unemployment and recovery by re-employment was estimated by logistic regression with covariances deduced from the labour market theories of human capital and segmented labour market. SETTING: Four municipalities in Greenland, southern Norway. SUBJECTS: Participants were a random sample of 17 to 63 year old people registered as unemployed for more than 12 weeks. MAIN RESULTS: In the cross sectional study, the prevalence of depression, anxiety, and somatic illness was from four to 10 times higher than in a control group of employed people. In the follow up study, there was considerable health related selection to re employment. A psychiatric diagnosis was associated with a 70% reduction in chances of obtaining a job. Normal performance on psychometric testing showed a two to three times increased chance of re-employment. Recovery of health following re-employment was less than expected from previous studies. CONCLUSIONS: Health related selection to long term unemployment seems to explain a substantial part of the excess mental morbidity among unemployed people. An increased proportion of the long term unemployed will be vocationally handicapped as years pass, putting a heavy burden on social services. PMID- 8436886 TI - The epidemiology of burns in rural Ethiopia. AB - STUDY OBJECTIVE: The aims were (1) to review inpatient burn records of Attat Hospital (Ethiopia) for the years 1983-1989, and (2) to determine the prevalence of burns and knowledge of first aid for burns in 16 communities served by Attat Hospital in rural Ethiopia. DESIGN: A retrospective review of all records was used to describe characteristics of the inpatient with burns and cost of the service. Adult members of a systematic random sample (20%) of households from 16 communities (total population = 10,183) were interviewed. Questions focused on what to do to put out the fire, what to do for first aid for a burn, the major cause of adult and childhood burns, and a history of burn in any household member. SETTING: The study was conducted at Attat Hospital and in the surrounding Gurage-Chaha Region of West Shoa Province of Ethiopia. STUDY SUBJECTS: There were 271 burn inpatients during the 7 year period from 1983-1989; 163 households were selected for interview; there were no refusals. MAIN RESULTS: During the 7 year period the cost of tertiary inpatient burn treatment at Attat Hospital has been estimated to be US$86,366.72, of which the hospital absorbed 66%. From community based information the cumulative incidence of burns in this population was found to be 5-11%. The absence of a cumulative increase in burns over time in men suggests that female respondents may not fully recall burn histories in adult male household members. The study population possess inadequate knowledge regarding burn prevention and burn first aid. Deleterious traditional compounds were used on 32% of burn patients in the villages. CONCLUSIONS: Since most burns are related to household fires, generally in the domain of women in rural Ethiopia, women's groups may be the most appropriate setting for education on burn prevention and first aid. Burn prevention and first aid education should also be recognised as a priority in schools and in the training of community health workers. PMID- 8436887 TI - Cardiovascular disease. PMID- 8436888 TI - Aetiological factors in persistent sputum production: a case-control study. AB - STUDY OBJECTIVE: The aim was to explore the aetiological roles of smoking, occupational exposure, childhood respiratory illness, and atopy in persistent sputum production. DESIGN: This was a case-control study. Data were obtained using a questionnaire administered by two observers blind to the subjects' status. Information was sought on lifetime smoking, occupation, hospital admissions due to respiratory disease, and respiratory disease history. SETTING: Four general practices in south east England in 1990, with a total population of about 30,000. SUBJECTS: Cases were subjects aged 5 to 54 years with sputum production; one control was selected per case, matched by general practice, age, and sex, forming 210 matched pairs (88% response rate). MAIN RESULTS: Cigarette smoking remains an important cause of persistent sputum production: the odds ratio (95% confidence interval) for current smoking was 7.9 (3.6-20.4). A dose response relationship was confirmed, with falling risk estimates after stopping smoking. The association of sputum production with occupational exposure to respiratory irritants, which was independent of smoking, was confined to men (odds ratio 2.4, 1.0-6.0) and largely attributable to very heavy exposure. Examination of the relationship with early respiratory disease suggested that much, though not all, was attributable to wheezing illnesses first manifest in childhood. CONCLUSIONS: Aetiological fractions derived from the results suggest that in the general population of south east England approximately 68% of all cases of persistent sputum production can be independently attributed to current cigarette smoking, 17% to heavy occupational exposure to respiratory irritants, and 13% to wheezing illnesses first manifest in early childhood. PMID- 8436889 TI - Oral contraceptive use among young women in southern Sweden. AB - STUDY OBJECTIVE: The aim was to survey oral contraceptive usage among women under 25 years of age. DESIGN: This was a cross sectional population study based on information collected by questionnaire mailed to randomly selected individuals. SETTING: The study population consisted of Swedish women born between 1960 and 1964 and living in the southern Swedish health care region which has about one and a half million inhabitants. PARTICIPANTS: The sample consisted of 3477 women, of whom 2573 or 74% agreed to participate in the study and were interviewed between November 1990 and April 1991. MAIN RESULTS: Of the 2573 women participating, 2254 (88%) reported having used oral contraceptives at some time, 77% of them having started during their teens. Teenage start of oral contraceptive use was found to be related to a lower age at menarche, a higher marriage/cohabitation rate, a lower rate of teenage full term pregnancy, a higher rate of spontaneous abortion, a lower frequency of teetotalism, and a higher frequency of smoking. Longterm use of antipsychotic drugs appeared to be less common among women who started oral contraceptive use early, but no relationship with other pharmaceutical drug usage was found. No relationship was found between oral contraceptive use and the presence of a first degree relative with cancer. CONCLUSIONS: A large proportion of Swedish women start using oral contraceptives during their teens, and report long duration of usage both before their first full term pregnancy and before the age of 25 years. The few women who have never used oral contraceptives do not appear to be representative of the general population. PMID- 8436891 TI - Chronic respiratory diseases. PMID- 8436890 TI - Induced abortions, miscarriages, and tobacco smoking as risk factors for secondary infertility. AB - STUDY OBJECTIVE: The aim was to determine whether induced abortions could increase the risk of secondary infertility. DESIGN: This was a case-control study; cases were women with secondary infertility, individually matched to two controls who were currently pregnant. Each participant was interviewed by one of two medical doctors using a questionnaire that sought information on their demographic, socioeconomic, medical, and reproductive status. The data were analysed by conditional logistic regression. SETTING: The study took place in the Alexandra Maternity Hospital in Athens, Greece, in 1987-88. PARTICIPANTS: 84 women consecutively admitted with secondary infertility and 168 pregnant controls took part. MAIN RESULTS: Eight cases and no controls reported a previous ectopic pregnancy, confirming that the occurrence of a pregnancy of this type dramatically increases the risk of secondary infertility. Furthermore, the occurrence of either induced abortions or spontaneous abortions independently and significantly increased the risk of subsequent development of secondary infertility. The logistic regression adjusted relative risks (and 95% confidence intervals) for secondary infertility were 2.1 (1.1-4.0) when there was one previous induced abortion and 2.3 (1.0-5.3) when there were two previous induced abortions. Tobacco smoking significantly increased the risk of secondary infertility, the adjusted relative risk being 3.0 (1.3-6.8). CONCLUSIONS: Legalised induced abortions, as currently practised in Greece, appear to increase slightly the relative risk of secondary infertility. PMID- 8436892 TI - Changing trend of neural tube defects in eastern Turkey. AB - STUDY OBJECTIVE: The aim was to study the relationship between birth prevalence of neural tube defect (including anencephaly) in Eastern Turkey before and after the Chernobyl disaster. DESIGN: This was a prospective study of time trends in live births and stillbirths over the years 1985-1990. Medical and sociodemographic data were recorded for the mothers. SETTING: Elazig, Eastern Turkey. SUBJECTS: There were 5240 live births and stillbirths during the study period, 24 of whom had neural tube defect and of these 20 had anencephaly. MAIN RESULTS: Of the 5240 newborns, 24 had a neural tube defect, giving a birth prevalence of 4.5 per 1000 total births. Of these, 20 were anencephalic (3.8 per 1000). In all, of the 2355 conceptions estimated to have occurred prior to the Chernobyl disaster in May 1986, the birth prevalences of total neural tube defect and anencephaly were the same (1.7 per 1000). This contrasts with the years following after Chernobyl, when the birth prevalence of total neural tube defect was 6.9 per 1000 (5.5 per 1000 for anencephaly). The differences were statistically significant (p < 0.001). These two increased rates reached a peak of 12.4 (for total neural tube defects) and 8.9 (for anencephaly) in 1988. In 1989 the rate of total neural tube defects decreased to 10.0 and that of anencephaly to 8.6 per 1000. In 1990 the rate of total neural tube defects fell to 5.6 and that of anencephaly fell to 4.2. CONCLUSIONS: The changes in birth prevalence of neural tube defects might be due to the Chernobyl disaster. However, the increases observed occurred mainly in infants conceived well over a year after the Chernobyl disaster, suggesting that other factors may be responsible. PMID- 8436893 TI - Prevalence of age related macular degeneration in persons aged 50 years and over resident in Australia. AB - STUDY OBJECTIVE: The aim was to determine, employing non-invasive procedures, the prevalence of age related macular degeneration in persons 50 years of age and over. DESIGN: A clinical investigation and a retrospective examination of ophthalmological records were employed in this study. SETTING: The study was conducted over the period 1988 to 1990 in the Western Metropolitan Health Region of New South Wales, Australia. PARTICIPANTS: A total sample of 3283 subjects stratified by local government area, age, and sex was obtained from the source population. It proved possible to confirm ophthalmological diagnoses in only 2522 of these subjects. MAIN RESULTS: All data were collected using accepted ophthalmological procedures and all diagnoses were confirmed through the use of independently derived ophthalmological records. A total of 428 subjects (13.0%) had a confirmed symmetrical diagnosis of age related macular degeneration. A total prevalence for diseased eyes of 14.9% was obtained. Prevalence of diseased eyes rose from 10.4% in those 50 to 64 years of age to 31.0% in those 85 years of age and over. CONCLUSIONS: There are several sources of error which can affect such a large sample study and are identified. Despite these, the prevalence rates obtained in this study provide normative rates for age related macular degeneration for persons 50 years of age and over. PMID- 8436894 TI - Sunlight exposure, antioxidant status, and cataract in Hong Kong fishermen. AB - STUDY OBJECTIVES: The aim was to test whether cataract is associated with higher lifetime exposure to sunlight, and whether antioxidants protect against cataract. DESIGN: This was a cross sectional survey of eye disease, with assessment of antioxidant status in a subgroup. SETTING: Hong Kong fishing communities in 1989. PARTICIPANTS: 685 men and women aged 55 to 74 years old were included in the study, of whom 367 (54%) attended hospital for detailed examination. MEASUREMENTS AND MAIN RESULTS: At a mobile clinic visual acuity and lens opacities were assessed, and using a questionnaire, occupational history and lifetime exposure to sunlight. At hospital ophthalmic measurements were repeated and blood was taken for measurement of plasma vitamin C, vitamin E, and total carotenoids, and red cell activities of glucose-6-phosphate dehydrogenase, glutathione peroxidase, superoxide dismutase, and catalase. Higher grades of cataract (particularly nuclear cataract) tended to be more common in subjects with the most sun exposure, although not to the point of statistical significance. In contrast to earlier studies, no association was found with antioxidant status. CONCLUSIONS: The findings give some support to the hypothesis that sunlight causes cataract. The absence of a relation to antioxidant status may be because blood levels of antioxidants at one point in time do not adequately reflect a subject's past metabolic state, and particularly the past activity of antioxidants in the lens. PMID- 8436895 TI - Education, reading, and familial tendency as risk factors for myopia in Hong Kong fishermen. AB - STUDY OBJECTIVE: The aim was to assess the influence of childhood reading on the development of myopia after allowance for familial differences in susceptibility. DESIGN: The study was a cross sectional survey. SETTING: Four fishing harbours in Hong Kong in 1989. SUBJECTS: Participants were 408 men and women aged 15-39 years old from 159 families. MAIN RESULTS: Histories of school attendance and reading habits in childhood were obtained at interview. Myopia was assessed by retinoscopy. Associations between myopia (defined as a refractive error of at least -1.0D in one or both eyes) and indices of reading in childhood were explored. Myopia was more common in subjects who had attended school (odds ratio = 1.7, 95% CI 1.0-3.0), with the highest risks in those who had started school at the earliest ages and who had spent the most time reading and writing while at primary school. Allowance for familial tendency to myopia produced no diminution in the risks associated with reading. CONCLUSIONS: These data support the hypothesis that reading in childhood is a cause of short sight. PMID- 8436896 TI - A birth cohort analysis of the smoking epidemic in West Germany. AB - STUDY OBJECTIVE: The aim was to provide insights in the spread of the smoking epidemic and eventual progress against cigarette smoking in West Germany. DESIGN: This was a retrospective birth cohort analysis based on a cross sectional national survey. SETTING: The survey was conducted in 1987 by the Ministry of Youth, Family and Health in order to identify priorities for health policy and promotion. The target population were all residents of German nationality above the age of 14 years. STUDY POPULATION: 1721 men and women of the birth cohorts 1911-20, 1921-30, 1931-40, 1941-50, 1951-60, and 1961-70 were included in this analysis (65.7% overall response rate). MEASUREMENTS AND MAIN RESULTS: The participants were asked for their detailed life time history of cigarette smoking in a personal interview. This information was used to calculate and plot historical smoker prevalences by sex, level of school education, birth cohort, and calendar year after correcting for differential survival of smokers and non smokers. In men, smoking prevalences increased slowly from birth cohort to birth cohort and reached a maximum of more than 70% in the 1941-50 cohort in the early 1970s. While smoker prevalences were considerably lower in the two youngest birth cohorts among better educated men, no major changes were observed in men with lower educational status. The rise of the smoking epidemic in women seems to have levelled off only very recently. CONCLUSIONS: In contrast to other countries with more powerful antismoking campaigns, no major progress in the fight against cigarette smoking has so far been made in West Germany. Major public health efforts are badly needed to limit the epidemic of smoking attributable diseases in this country. PMID- 8436898 TI - The work of the Central Health Monitoring Unit in the Department of Health (England). PMID- 8436897 TI - Mortality among injecting drug users: a critical reappraisal. AB - STUDY OBJECTIVE: The aim was to quantify all cause mortality among injecting drug users. DESIGN: This was a retrospective analysis of 1989 data on injecting drug users and mortality obtained from three independent agencies: the Procurator Fiscal's Office, the General Register Office, and the Scottish HIV-test register. SETTING: Greater Glasgow, Scotland. SUBJECTS: Drug injectors, estimated population 9424. MAIN RESULTS: 81 names were found using the three sources to identify deaths. After removing duplicates, 51 deaths were found. This represented a mortality rate of 0.54% in the estimated population. Among female injectors the mortality rate was 0.85%, significantly higher than the rate of 0.42% among male injectors (95% CI for the true difference in mortality rates between female and male injectors was 0.31%-0.55%). Over 90% of deaths were attributed to overdose or suicide. Although AIDS caused only one death, 19% of cases (5/27) whose HIV antibody status could be ascertained were positive. The mortality rate among HIV positive injectors (3.8%) was significantly higher than among HIV negative injectors (0.49%). CONCLUSIONS: Comprehensive coverage using three data sources revealed a far greater annual number of all cause deaths among injectors than would have been expected from previous research. The observed mortality rate was lower than in previous studies where the denominators used to calculate rates had an element of underenumeration. For the foreseeable future it is unlikely that AIDS will have much impact on mortality among injectors in Glasgow, because of the low prevalence of HIV infection among injectors in the city, and because HIV positive injectors are dying for reasons other than AIDS; rather, overdose and suicide will continue to be the main causes of death. PMID- 8436899 TI - Contagious suicide in prisons and police cells. AB - STUDY OBJECTIVE: The aim was to determine whether clustering of suicide occurred in prisoners and detainees in police cells and to describe the characteristics of any clusters identified. DESIGN: Mortality from suicide was examined for evidence of clusters. SETTING: Prisons (1971-1988) and police cells (1980-September 1991) in New Zealand. SUBJECTS: 82 male suicides. MAIN RESULTS: There were 38 male suicides in prisons and 44 in police cells over the time periods. Due to the increasing trend in prison suicides, the 1971-1982 and 1983-1988 time periods were examined for evidence of clusters separately. For suicides in police cells the time periods studied were 1980-1982, 1983-1988, and 1989-1991. The event of suicide was treated as a Poisson process with all suicides in a time period used to calculate the mean. Four suicide clusters occurred between 1985 and 1988 in prisons. These did not explain the increased suicide rate over this period. Three clusters of suicide in police cells occurred between 1980 and 1991, which had different characteristics from suicide in prisons in that these three clusters were of longer duration. CONCLUSIONS: The different characteristics of prison and police cell clusters of suicide indicated separate transmission of the contagious component of suicide between these groups. Distinct strategies to reduce clusters of male suicide in custody are required for prisoners and those held in police cells. PMID- 8436900 TI - On the influence of data source in aggregated data studies: a comparative study of suicide information based on death certificates and judicial files. AB - STUDY OBJECTIVE: The aim was to assess the differences in suicide data obtained from different database sources. DESIGN: Death certificate based data on suicidal deaths were compared with the information obtained from the non-natural death investigation files at the Public Prosecutor's Office. SETTING: The study was confined to the time period of 1981-1984 and to the residents of the district of Leuven (Belgium) who died in the district. MAIN RESULTS: Differences were found in the number of suicidal deaths reported as well as in the demographic variables, the distribution of suicide methods, and the place of death. Sixty percent of the records in both databases could be matched for all variables studied (age, gender, civil state, place of death, and suicide method), and another 10% if only place of death was allowed to differ. For 4.5% of the cases in the judicial files and for 8% of the records in the official statistics database no corresponding record from the other data source could be found. Based on simple probability statistics [P(missing record)+P(different information[present)] the possible minimum global information bias could be estimated to range from 7 to 42%. CONCLUSIONS: Different epidemiological pictures of suicide mortality may result from studying different data sources. PMID- 8436901 TI - Selective migration by birthweight. PMID- 8436902 TI - Relationship between invariant chain expression and major histocompatibility complex class II transport into early and late endocytic compartments. AB - Invariant chain (Ii), which associates with major histocompatibility complex (MHC) class II molecules in the endoplasmic reticulum, contains a targeting signal for transport to intracellular vesicles in the endocytic pathway. The characteristics of the target vesicles and the relationship between Ii structure and class II localization in distinct endosomal subcompartments have not been well defined. We demonstrate here that in transiently transfected COS cells expressing high levels of the p31 or p41 forms of Ii, uncleaved Ii is transported to and accumulates in transferrin-accessible (early) endosomes. Coexpressed MHC class II is also found in this same compartment. These early endosomes show altered morphology and a slower rate of content movement to later parts of the endocytic pathway. At more moderate levels of Ii expression, or after removal of a highly conserved region in the cytoplasmic tail of Ii, coexpressed class II molecules are found primarily in vesicles with the characteristics of late endosomes/prelysosomes. The Ii chains in these late endocytic vesicles have undergone proteolytic cleavage in the lumenal region postulated to control MHC class II peptide binding. These data indicate that the association of class II with Ii results in initial movement to early endosomes. At high levels of Ii expression, egress to later endocytic compartments is delayed and class II-Ii complexes accumulate together with endocytosed material. At lower levels of Ii expression, class II-Ii complexes are found primarily in late endosomes/prelysosomes. These data provide evidence that the route of class II transport to the site of antigen processing and loading involves movement through early endosomes to late endosomes/prelysosomes. Our results also reveal an unexpected ability of intact Ii to modify the structure and function of the early endosomal compartment, which may play a role in regulating this processing pathway. PMID- 8436903 TI - Specific tolerance to neural allografts induced with an antibody to the interleukin 2 receptor. AB - Despite considerable evidence documenting the central nervous system as a site of immunological privilege, immune responses do occur within the brain and neural allografts between major histocompatibility complexes (MHC) and minor antigen incompatible rat strains may be rejected. The survival of completely MHC incompatible neural allografts has been found to be prolonged indefinitely after administration of a monoclonal antibody (mAb) to the interleukin 2 receptor (IL 2R) for 10 d after transplantation. Here we present evidence that rats with long term surviving lateral ventricular neural allografts, after anti-IL-2R treatment, accept subsequent neural allografts from the same donor strain, placed in a peripheral nonprivileged site, but rapidly reject third-party grafts. Thus, treatment with a mAb to the p55 chain of the IL-2R has resulted in the specific acceptance of second grafts of fully allogeneic neural tissue. These results suggest that ongoing interaction between elements of the host immune system and alloantigen within the brain maintains the tolerant state and furthermore, that interruption of signaling through the IL-2R may be important in allospecific tolerance induction. PMID- 8436904 TI - Human peripheral blood basophils primed by interleukin 3 (IL-3) produce IL-4 in response to immunoglobulin E receptor stimulation. AB - In contrast to most cytokines, interleukin 4 (IL-4) expression is restricted to T lymphocytes, with the exception of mast cell lines and mast cells, as more recently demonstrated in rodents. Little is known, however, about the capacity of human nonlymphoid cells to produce IL-4. In this study we show that mature human basophils are capable of expressing IL-4 and examine the regulation of IL-4 production in comparison with the lipid mediator leukotriene C4. IL-4 was produced upon immunoglobulin E receptor (IgER) activation of basophils cultured with IL-3, a cytokine previously shown to prime these cells for enhanced release of inflammatory mediators. In some experiments, IL-3 or IgER activation alone also induced IL-4 production close to the detection limit. The effect of IL-3 on IgER-dependent IL-4 expression was dose and time dependent: maximal IL-4 production occurred between 18 and 48 h preexposure of basophils to 3-10 ng/ml IL 3. IgER-induced IL-4 synthesis and release by basophils cultured with IL-3 was rapid and complete after 6 h. In contrast to IL-3, other cytokines (IL-5, granulocyte/macrophage colony-stimulating factor, and nerve growth factor) that also prime basophils for enhanced histamine and leukotriene C4 release did not promote IgER-induced IL-4 synthesis. Basophils appear to secrete a "TH2-like" cytokine profile since no detectable IL-2 or interferon gamma was produced upon IgER activation. Mononuclear cells (depleted of basophils), cultured in parallel, did not release IL-4 in response to IL-3 and/or IgER activation, and produced approximately ten times less IL-4 than basophils upon nonspecific activation by phorbol ester and calcium ionophore. Thus, human basophils are an important cellular source of IL-4, and may, therefore, in addition to their inflammatory effector functions, also regulate the differentiation of T helper cells and B cells, in particular in allergic diseases. PMID- 8436905 TI - Changes in the repertoire of peptides bound to HLA-B27 subtypes and to site specific mutants inside and outside pocket B. AB - HLA-B27 subtypes share many structural features, including their pocket B, which interacts with a conserved Arg residue at the second position of B*2705-bound peptides. Subtypes differ among each other at other locations in the peptide binding site. In this study, metabolic labeling and radiochemical pool sequencing were used to address the following issues: (a) presence of the Arg 2 (R2) motif among peptides bound to the various HLA-B27 subtypes; (b) influence of mutations inside and outside pocket B on this motif; and (c) the degree of similarity among the peptide pools bound to the various B27 subtypes. Sequencing of Arg-labeled peptide pools extracted from B*2701 to B*2706, and from two site-directed mutants of B*2705 with changes outside pocket B, indicated that all of these molecules bind peptides with Arg at position 2. Peptides from several mutants with changes altering the structure of pocket B, and from one mutant at the pocket B rim, also retained the R2 motif. However, this was absent in the peptide pool extracted from the M45 mutant, in which the negative charge of pocket B, conferred to HLA B27 by Glu45, was canceled. These results indicate that alterations outside pocket B, and even disruption of the network of hydrogen bonds that stabilizes Arg binding in pocket B, do not impair binding of peptides bearing the R2 motif, but a nonconservative substitution at position 45 does. As a substantial fraction of anti-B*2705 cytotoxic T lymphocyte (CTL) clones crossreact with the M45 mutant (Villadangos, J., B. Galocha, D. Lopez, V. Calvo, and J. A. Lopez de Castro. 1992. J. Immunol. 149:505) this result suggest that determinant mimicry by nonidentical peptides may frequently account for unexpected CTL crossreactions. Metabolic labeling with various other amino acids and radiochemical sequencing revealed similarities, but also substantial differences, among the peptide pools from the various HLA-B27 subtypes. This strongly suggests that many peptides bind to multiple subtypes, but significant subsets of peptides bound to a given HLA B27 subtype do not bind to other subtypes or do so with greatly altered efficiency. These results indicate the importance of polymorphism outside pocket B in modulating peptide binding to HLA-B27. PMID- 8436906 TI - B lymphocytes in vivo fail to prime naive T cells but can stimulate antigen experienced T lymphocytes. AB - The ability of B cells or macrophages and dendritic cells (DC) to elicit class II restricted T cell responses in vivo was compared using a mouse chimera model. Severe combined immunodeficient (SCID) mice (H-2d), reconstituted either with T or T+B lymphocytes from (H-2d x H-2b) donors, were immunized subcutaneously with protein antigen (Ag) to induce a class II-restricted T cell response. The frequency and major histocompatibility complex restriction of the resulting Ag specific T cells were analyzed to establish whether B cells were necessary for the induction of class II-restricted T cell responses, and to determine the cell type on which priming had occurred. The results indicated that: (a) B cells are not necessary for the induction of a class II-restricted T cell response in vivo, as the frequencies of interleukin 2 (IL-2)- or IL-3-secreting T cells induced in the presence or absence of B cells were comparable. (b) Activation of naive T cells requires presentation of Ag on DC; Ag presented only on B cells is not sufficient to elicit a response. No H-2b-restricted, IL-3-secreting cells could in fact be detected in SCID mice reconstituted with naive (H-2d x H-2b) T cells and nonimmune or antigen-primed (H-2d x H-2b) B cells. (c) Previously primed T cells are able to be stimulated by Ag presented by both B cells and DC. H-2b restricted, IL-3-secreting cells could in fact be readily demonstrated in SCID mice reconstituted with antigen-primed (H-2d x H-2b) T and B cells. Irrespective of whether the T cells were naive or previously activated, B cells were able to respond with an Ag-specific immunoglobulin G response, indicating that B cells were functional and able to present Ag in order to receive specific T cell help. Therefore, it appears that B cells are not necessary and do not participate in the initial priming of T cells; however, Ag presented by B cells can reactivate previously primed T cells. Taken together, these data indicate that during the course of an immune response Ag is first presented to naive T cells via DC, and only subsequently primed T cells can be stimulated by Ag presented by B cells. PMID- 8436907 TI - Repression of major histocompatibility complex IA expression by glucocorticoids: the glucocorticoid receptor inhibits the DNA binding of the X box DNA binding protein. AB - Glucocorticoids are effective repressors of major histocompatibility complex (MHC) class II gene expression. The repression occurs in B cells, which constitutively express MHC class II, as well as in macrophages, which only express MHC class II after the cells are treated with interferon gamma. For the MHC class II gene IA beta, this negative regulation has been linked to the X box DNA sequence, located with the IA beta promoter. The addition of the glucocorticoid receptor was shown to inhibit the DNA binding of the X box DNA binding protein to the X box. The DNA binding of two other DNA binding proteins that recognize elements within this promoter was unaffected by the addition of glucocorticoid receptor. It is likely that the repression of IA beta gene expression by glucocorticoids occurs because the X box DNA binding protein is prevented from binding to the DNA and activating transcription. PMID- 8436908 TI - Interleukin (IL) 4 differentially regulates monocyte IL-1 family gene expression and synthesis in vitro and in vivo. AB - Interleukin (IL) 4 is a multifunctional T cell-derived cytokine that inhibits cytokine production and certain effector functions in human monocytes, while enhancing others. We show that IL-4 may contribute to the downregulation and resolution of an inflammatory response by selectively promoting expression of the IL-1 receptor antagonist (IL-1ra) that blocks the action of IL-1. IL-1ra specifically binds to the IL-1 receptor without initiating signal transduction. Peripheral blood monocytes obtained from cancer patients, before and immediately after a regimen of IL-4 immunotherapy, were examined for IL-1ra gene expression. After IL-4 therapy, monocytes from the patients showed a marked increase in IL 1ra mRNA. This selective induction of IL-1ra mRNA in circulating monocytes was reflected by significantly enhanced serum levels of IL-1ra (p < 0.01) during IL-4 therapy, which declined after IL-4 treatment. In vitro analysis of IL-4 regulation of monocytes from normal individuals revealed a dose-dependent induction of IL-1ra mRNA within 2-4 h after stimulation without a concomitant effect on the expression of IL-1 mRNA. Increased IL-1ra mRNA was not due to RNA stabilization, but occurred at the level of transcription. In the presence of LPS, IL-4 not only augmented IL-1ra levels, but markedly inhibited LPS-induced IL 1 mRNA expression. The selective upregulation of IL-1ra by resting or activated monocytes, coupled with inhibition of IL-1 production by activated monocytes, as we demonstrate both in vitro and in vivo, suggests that IL-4 may prove clinically useful as a systemic antiinflammatory agent. PMID- 8436909 TI - Differentiation-stage specific self-peptides bound by major histocompatibility complex class I molecules. AB - We have tested the hypothesis that phenotypic changes of development are accompanied by expression of differentiation-stage specific peptides bound to major histocompatibility complex (MHC) class I molecules. The U937 cell line, when cultured in the presence of phorbol myristate acetate (PMA), undergoes differentiation from monoblasts to macrophage-like cells. The high-performance liquid chromatography profile of peptides eluted from purified human histocompatibility leukocyte antigen class I molecules expressed by U937 treated with PMA differs from that obtained from control, untreated U937 cells. Chemical sequencing of eluted peptides identified a peptide derived from cytomegalovirus in both treated and untreated cells. PMA-treated, but not untreated cells, displayed an additional peptide derived from interleukin 1 beta. Hence, differentiation-induction of U937 is accompanied by the presentation of at least one differentiation-stage specific peptide. Our results indicate that, similar to viral infection, cellular development and transformation is accompanied by the de novo synthesis of proteins which are processed and presented on MHC class I molecules. PMID- 8436910 TI - Hypermutation is observed only in antibody H chain V region transgenes that have recombined with endogenous immunoglobulin H DNA: implications for the location of cis-acting elements required for somatic mutation. AB - Mice with transgenes containing an antibody H chain V region (VHDJH) gene were used in an analysis of the cis-acting elements required for hypermutation of immunoglobulin (Ig) V genes. These transgenes can somatically recombine with endogenous IgH DNA, leading to the formation of functional heavy (H) chains partially encoded by the transgenic VHDJH. The transgenomes in the five different lines of mice analyzed contain as little as 150 bp, and as much as 2.8 kb of natural DNA flanking the 5' side of the VH and either 1.5 or 2.3 kb (including the intronic enhancer and 5' matrix attachment region [MAR]) flanking the 3' side of VH. Hybridomas were constructed from immunized transgenic mice, and transgenes present in these hybridomas that had or had not recombined to form functional H chain loci were sequenced. The data obtained show that: (a) the recombined transgenes contain hypermutated VH genes; and (b) among such transgenes, even those containing only 150 bp of natural VH 5' flanking sequence and several kilobases of 5' plasmid vector sequence display a frequency, distribution, and type of mutation characteristic of conventional IgH loci. The data also indicate that transgenic VHDJH genes that have not recombined with endogenous IgH DNA are not substrates for hypermutation, even if they are flanked by 2.8 kb of natural 5' DNA, and 2.3 kb of natural 3' DNA, including the JH2-JH4 region, a MAR, and the intronic enhancer. Collectively, the data suggest that sequences 5' of the VH promoter are dispensable, a VH promoter and the intronic IgH enhancer region are not sufficient, and a region(s) within or 3' of the IgH constant region locus is requisite, for hypermutation of Ig VH transgenes. PMID- 8436911 TI - T cell receptor selection by and recognition of two class I major histocompatibility complex-restricted antigenic peptides that differ at a single position. AB - Peptides derived from HLA-Cw3 and HLA-A24 within region 170-179 differ by a single substitution, at position 173, and are both presented by the class I major histocompatibility complex molecule H-2Kd for recognition by murine cytolytic T lymphocytes (CTLs). As a first approach to understand the way T cell receptors (TCRs) intact with the HLA peptides, we have analyzed the TCR selection by, and recognition of, the two HLA antigenic sites. First, we have compared the TCR repertoires selected by HLA-Cw3 and HLA-A24, not only by sequencing the TCRs carried by CTL clones isolated and grown in vitro, but also by analyzing the TCRs expressed in vivo by peritoneal exudate lymphocytes from immune animals. Second, we have compared the TCR crossrecognition of HLA-A24 by CTLs selected by HLA-Cw3 with that of HLA-Cw3 by CTLs selected by HLA-A24. The combined analysis of TCR selection by and recognition of these two related HLA antigenic sites provides evidence that the TCR beta junctional regions interact with the amino-terminal part of the HLA peptides. PMID- 8436912 TI - The concurrent maturation of mouse and human thymocytes in human fetal thymus implanted in NIH-beige-nude-xid mice is associated with the reconstitution of the murine immune system. AB - To determine whether the human thymus provides an environment for the maturation of murine T cells, human fetal thymus and liver (hu-thy/liv) were implanted into congenitally athymic NIH-beige-nude-xid (BNX) mice or C.B-17 scid/scid (SCID) mice. 3 mo after implantation, in contrast to the hu-thy/liv implant in SCID mice, which was populated only with human CD4/CD8 single- and double-positive thymocytes, the hu-thy/liv implant in BNX mice contained a chimeric population of human and mouse CD4/CD8 single- and double-positive thymocytes. Immunohistochemical staining of the hu-thy/liv implant in BNX mice indicated that the population of double-positive mouse thymocytes was localized to discrete areas of the human fetal thymus. Quantitative improvements in mouse T cell and immunoglobulin (Ig) G parameters were observed after grafting of the human fetal thymus and liver tissue into BNX mice. In addition, in contrast to the nonimplanted BNX mice, the implanted BNX mice were capable of mounting a keyhole limpet hemocyanin-specific IgG response and their peripheral T cells were responsive to stimulation with mitogens and antibodies directed to the T cell receptor. Furthermore, after in vivo priming, T cells present in lymph nodes of the implanted BNX mice were capable of mounting an antigen-induced in vitro T cell-dependent proliferative response. Thus, concurrent with the continued maturation of human T cells, murine T cells differentiated within the human fetal thymus implanted in the BNX mice and mediated the phenotypic and functional reconstitution of the murine immune system. Mice with a reconstituted immune system that contain a human thymic implant that is infectible with human immunodeficiency virus (HIV) should prove useful in the investigation of T cell maturation in the thymus and in the evaluation of potential HIV vaccines. PMID- 8436913 TI - Adhesion to fibronectin prolongs eosinophil survival. AB - We have investigated the effect of adhesion to fibronectin (Fn) on the survival of eosinophils in culture. Peripheral blood eosinophils from normal human donors were separated by immunomagnetic selection and cultured in RPMI on Fn- (100 micrograms/ml) coated microtiter plates for up to 96 h. Survival was measured by trypan blue exclusion. There was a significant enhancement of eosinophil survival with Fn as compared with both bovine serum albumin-coated and uncoated wells (p < 0.05-0.01). Fn-induced eosinophil survival was comparable to that obtained with exogenous interleukin 3 (IL-3) or granulocyte/macrophage colony-stimulating factor (GM-CSF) and was inhibitable by antibodies against Fn, very late antigen 4 (VLA-4), IL-3, and GM-CSF. Supernatants from Fn-, but not BSA-coated wells contained picogram amounts of IL-3 and GM-CSF, and eosinophils cultured on Fn for 24 h expressed mRNA for GM-CSF as determined by in situ hybridization. Therefore, Fn prolongs eosinophil survival in culture by triggering autocrine generation of cytokines by eosinophils. Since neutrophils lack VLA-4, this could provide a partial explanation for the preferential accumulation of eosinophils at sites of allergic inflammation, as well as the predominant tissue localization of eosinophils in healthy individuals. PMID- 8436914 TI - Abnormal transcription factor induction through the surface immunoglobulin M receptor of B-1 lymphocytes. AB - Populations of murine peritoneal B-1 and splenic B-2 cells, highly purified by negative selection techniques, were used to demonstrate that B-1 cells completely fail to enter cell cycle in response to surface immunoglobulin M (sIgM) crosslinking without any decrease in cell number or viability. This failure of B 1 cell responsiveness appears to represent a specific defect in sIgM-derived signaling inasmuch as stimulation to enter S phase occurs normally in response to activated and fixed T cells, and to lipopolysaccharide (LPS). The level at which sIgM signaling fails was determined by evaluating the nuclear expression of the transcription factor complex, NF-kappa B, whose sIgM-mediated induction in B-2 cells is dependent on protein kinase C (PKC) activation but is independent of protein synthesis. There was no induction of nuclear NF-kappa B in B-1 cells stimulated by sIgM crosslinking, although NF-kappa B was stimulated by phorbol myristate acetate and by LPS. In contrast, NF-kappa B was induced in B-2 cells by all three stimuli. Thus, in B-1 cells, the sIgM-mediated induction of a transcription factor that is substantially stimulated by anti-IgM in B-2 cells is blocked. However, all sIgM-derived signaling in B-1 cells was not impaired inasmuch as anti-IgM increased I-A antigen expression. These results strongly suggest that sIgM receptor-mediated signaling in B-1 cells is interrupted early in the signal transduction pathway, at a point proximal to the activation of PKC. These results further demonstrate that transcription factor induction can be used to analyze the level at which receptor-mediated signaling is blocked. PMID- 8436916 TI - Uncoupling the correlates of locomotor costs: a factorial approach. AB - Although the metabolic cost of running has been found to vary systematically with running speed and body mass in animals, no mechanistic model of cost determination has been widely accepted. Because two suggested cost determinants- mechanical power output and the rate of force application--covary with running speed when gait (stride frequency) is unconstrained, examining the influence of each factor on cost has been problematic. We experimentally uncoupled the usual relationships between three readily manipulated cost correlates--speed, stride frequency, and mass distribution--to study the determinants of the cost of running in humans along a section of the cost response surface. Two levels of each cost correlate were used in a factorial design in which subjects ran at all eight combinations of factor levels while rate of oxygen consumption (VO2), mechanical power, and contact time were measured as response variables. Contact time and mechanical power were measured from high-speed cinefilm. Mechanical power accounted for 88%, and contact time (rate of force application) 57%, of speed-related VO2 variation. Variation in cost produced by changes in stride frequency and mass distribution were largely explained by mechanical power. Contact time was not significantly correlated with overall variation in VO2, while mechanical power output explained 80% of that variation. For the range of conditions tested, we conclude that the mechanical power derived from muscular contractions is an important determinant of the cost of running. While we have shown that the rate at which muscles shorten is not the sole determinant of the cost of running, the extent to which this factor influences cost remains unclear. PMID- 8436915 TI - Changes at peptide residues buried in the major histocompatibility complex (MHC) class I binding cleft influence T cell recognition: a possible role for indirect conformational alterations in the MHC class I or bound peptide in determining T cell recognition. AB - Recent crystallographic studies on two peptide complexes with the mouse Kb molecule have shown that peptide binding appears to alter the conformation of the class I alpha-helical regions that flank the antigen binding cleft. Given that this study also showed that much of the foreign peptide is buried within the class I binding cleft with only a small portion accessible for direct interaction with the components of the T cell receptor, this finding suggests that at least some component of T cell specificity may arise as a consequence of peptide induced conformational changes in the class I structure. To assess this possibility, we have made systematic substitutions at residues within the Kb restricted determinant from ovalbumin (OVA257-264) that are thought to be buried on binding to the class I molecule. We have found that changes in this determinant at the completely buried second residue (P2) can influence T cell recognition without affecting binding to Kb, suggesting that the substitutions may indirectly determine T cell recognition by altering the conformation of the class I molecule or the bound peptide. PMID- 8436917 TI - Progestins inhibit murine oocyte meiotic maturation in vitro. AB - The in vitro culture of fully grown mammalian oocytes results in spontaneous meiotic maturation from prophase arrest to metaphase II. This maturation can be inhibited by steroid hormones in both murine and porcine oocytes. Using selected steroids, we have examined the structure-activity relationships of steroids and oocyte inhibition. Experiments with androgens, estrogens, glucocorticoids, and progesterone revealed that at least one steroid from each class was inhibitory. Progesterone, however, was two to three times more effective than steroids from other classes. Examination of a variety of progestins showed that most substitutions decreased or abolished the inhibitory activity. Hydroxy group substitutions at different carbon atoms and substitutions at the 4-ene group lessened the inhibitory effectiveness, with the exception of 5 beta dihydroprogesterone, which was as effective as progesterone. However, several steroids with substitutions at the C17 acetyl group were more active than progesterone, including 20 beta-dihydroprogesterone which was the most inhibitory steroid tested (ID50 = 5 microM). The progesterone agonist R5020 was also very active (ID50 = 8 microM). This is the first report of a detailed examination of the steroid-induced inhibition of murine oocytes. A comparison between the results reported here and previous reports of steroid-induced inhibition in porcine oocytes reveals differences in the response of oocytes from the two families. The structure-activity relationships of the inhibitory steroids examined here suggest that the steroids are acting via a receptor-mediated system. PMID- 8436918 TI - Gonadal differentiation and secretions of estradiol and testosterone of the ovaries of Rana catesbeiana tadpoles treated with 4-hydroxyandrostenedione. AB - Laparotomized female tadpoles of Rana catesbeiana at TK stages X-XII, about 9 months old, were implanted intraperitoneally with empty capsules or capsules containing 4-hydroxyandrostenedione (4-OHA), known as an aromatase inhibitor in vertebrates. Histology, gonosomatic index, and secretions of estradiol (E2) and testosterone (T) of the ovaries were investigated. Three months after the treatment, histological examination revealed various degrees of sex reversal in the ovaries treated with 4-OHA and 79% (57 in 72) were transformed into testes. The ovaries of control tadpoles, however, displayed normal histological appearance. Radioimmunoassay showed that secretion of E2 was decreased while that of T was increased in 4-OHA treated ovaries. The gonosomatic index displayed a decline tendency from control females through experimental animals to untreated control males. These results indicated that activity of aromatase in the ovaries was inhibited by 4-OHA, resulting in accumulation of T which induced transformation of the ovaries into testes. PMID- 8436919 TI - The yolk syncytial layer of Fundulus: its origin and history and its significance for early embryogenesis. AB - Because of its importance in early embryogenesis, the developmental history of the yolk syncytial layer (YSL) of Fundulus has been investigated in detail. As in other teleosts, the Fundulus YSL forms mainly by collapse of certain marginal blastomeres which then merge with the cytoplasm of the yolk cell peripheral to the blastoderm. Nuclei enter the yolk cell from these open blastomeres variably during cleavages 8-11, but most frequently at cleavages 9 and 10. After entry, the first nuclei divide five times and later nuclei divide with them. Thus, nuclei that have invaded at the next cleavage divide four times, etc. When the first YSL nuclei cease dividing, all other YSL nuclei cease dividing with them. These YSL mitoses occur in metachrony. Two or more metachronous waves progress through the YSL cytoplasm at each mitosis. After each nuclear division, the YSL increases in width and its nuclei are quite evenly spaced. After the 5th and last mitosis, when the YSL is at its widest, it contracts in its animal-vegetal axis. This slow contraction has two major effects: 1) narrowing of the YSL, accompanied by crowding of its nuclei and their disappearance beneath the blastoderm to nucleate the internal YSL; 2) epibolic expansion of the I-YSL and the blastoderm, followed soon after by other cell movements of gastrulation. This YSL transition, therefore, sets the stage for the onset of gastrulation. It is preceded by increased duration and variability of succeeding mitoses and, in particular, duration of their interphases, a decrease and deceleration in the rate of the last metachronous waves, and, finally, by the complete cessation of mitosis and the entry of YSL nuclei into permanent interphase. PMID- 8436920 TI - Embryonic mouse pre-metatarsal development in organ culture. AB - Embryonic mouse pre-metatarsals were removed from embryos at 13 days of gestation and cultured in a defined, serum-free medium for up to 15 days. By histological analysis, we observe that the cultured pre-metatarsal tissue undergoes a similar developmental profile as pre-metatarsals growing normally in vivo. The initial mesenchyme condensation regions undergo differentiation and morphogenesis to form distinct rods made up of cartilage tissue. A marker of this differentiation step is the synthesis of type II collagen. Metabolic labelling, pepsin digestion, SDS PAGE, and autoradiography were used to demonstrate this protein when cartilage tissue is present in the cultures. After additional culture time, terminal chondrocyte differentiation and morphogenesis take place in specific regions of the cartilage rods to form bands of hypertrophied chondrocytes. One marker of this differentiation step is the synthesis of the enzyme alkaline phosphatase. We have measured the activity of this enzyme throughout the culture period and see a substantial increase at the time of terminal chondrocyte differentiation. Another feature of hypertrophied chondrocytes is that the matrix around the cells becomes calcified. Calcified matrix in our cultured pre-metatarsals was visualized by staining with alizarin red. By supplementing the defined culture medium with ITS, we observed that terminal chondrocyte differentiation took place in a shorter culture time. Supplementation of the medium with serum results in a similar acceleration of terminal differentiation, and, with additional culture time, an osteoid-like matrix forms around the central region of the rods. PMID- 8436921 TI - Mapping of the chicken N-CAM gene and a myosin heavy chain gene: avian microchromosomes are not genetically inert reserves of DNA. AB - Physical mapping of the chicken neural cell adhesion molecule gene and of a chicken myosin fast-white heavy chain gene via in situ hybridization has assigned both loci to different-sized microchromosomes in this species. Two genomic cloned chicken DNA probes of 16 kb (lambda cN6) and 15 kb (DCM 11), respectively, were biotin labeled for fluorescent detection of the genes. The implications derived from these results, together with further data just now beginning to accumulate regarding the genetic content of avian microchromosomes, confirm an unexpectedly active role for these minute chromosomes. PMID- 8436922 TI - Primitive sex chromosomes in poeciliid fishes harbor simple repetitive DNA sequences. AB - The demonstration of the chromosomal mode of sex determination via genetic experiments as well as the absence of heteromorphic sex chromosomes affirm poeciliid fishes as a unique group among vertebrates that are endowed with the most primitive form of sex chromosomes. In many different taxa the evolutionary process involved in the differentiation of advanced sex chromosomes is outlined through sex specifically organized repetitive sequences. In this investigation hybridization of synthetic probes specific to genomic simple repeat motifs uncovers a sex-specific hybridization pattern in certain viviparous fishes of the family Poeciliidae. The hybridization pattern together with specific staining of the constitutive heterochromatin by C-banding reveals heterogamety in males (Poecilia reticulata) as well as in females (P. sphenops). In P. velifera, however, C-banding alone fails to unravel the heterogametic status. The female specific W-chromosome can be detected by simple repetitive sequence probes. Therefore, the principal significance of heterochromatization as a means of generating differentiated sex chromosomes is evident. PMID- 8436923 TI - Cumulus oophorus as a sperm sequestering device, in vivo. AB - The cumulus oophorus, unique to the egg of eutherian mammals, has been suggested to function either in egg transport to the oviduct ampulla, in avoidance of polyspermy, in enhancement of sperm fertilizing ability, or in sperm guidance to the egg. To examine its role further, the content of the oviduct ampulla was collected at 0700-0730 h, 1130-1200 h, or 1600-1700 h on the day of ovulation from rats mated once or more than once, and analysed with an emphasis on sperm distribution in the ampullary fluid, in the cumulus, and in the eggs. The distribution of spermatozoa between cumulus and ampullary fluid was highly skewed (ca. 9:1) at all times in favor of the cumulus. In 14.1% of the ampullae collected by 0730 h the only spermatozoa present were those already within eggs; and in many other ampullae then there were no more than one or so additional spermatozoa outside fertilized eggs--a testament to the efficiency of the mechanisms that ensure an early meeting of gametes in the oviduct. There was a gradual increase in the total number of spermatozoa in the ampulla throughout the day of ovulation, and the time of eventual cumulus dispersal later in the day generally reflected the number of spermatozoa within it, rather than the occurrence of fertilization per se. These observations suggest that the cumulus oophorus sequesters and brings to the immediate vicinity of the eggs the few spermatozoa which gain the ampulla at or soon after ovulation, so favoring early fertilization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8436924 TI - Aura of inevitability. PMID- 8436925 TI - Decline of generalists. PMID- 8436926 TI - A chart unchained. PMID- 8436927 TI - Blood banking and transfusion medicine. Past, present and future. PMID- 8436928 TI - Legal aspects of blood transfusion. PMID- 8436930 TI - Transfusion transmitted infectious diseases. AB - The best means to reduce transfusion-transmitted infections is to start with volunteer, unpressured, altruistic blood donors. Careful screening and use of a number of sensitive tests to detect asymptomatic carriers of various infections make blood transfusion quite safe today. However, there will never be a zero risk blood supply. Therefore, additional efforts should be made to transfuse patients appropriately as we seek safer alternatives to traditional transfusions. In the meantime, we should congratulate ourselves for having a very safe and good blood supply, which can help so many patients. PMID- 8436929 TI - Ethical aspects of blood transfusion. PMID- 8436931 TI - Noninfectious risks and new trends in transfusion practice. AB - HIV infection and hepatitis are considered major transfusion risks, but there are other serious adverse effects; circulatory overload, acute hemolytic transfusion reaction, and graft-versus-host disease. Each can be minimized by attention to preventative measures. Current transfusion practice emphasizes the appropriate use of selected components, promotion of autologous transfusions, single donor apheresis platelets, and intraoperative blood salvage. Blood cell growth factors are important in the management of patients with production disorders. Tracking of bones and tissues used as allografts will become an important function for health-care facilities. PMID- 8436932 TI - Red blood cell transfusions. PMID- 8436933 TI - Guidelines for blood component therapy. PMID- 8436934 TI - Total quality improvement. A lifetime goal. PMID- 8436935 TI - What does a hospital transfusion service expect from its blood center? PMID- 8436936 TI - Role of proficiency survey in blood bank quality control. AB - The College of American Pathologists' blood bank proficiency survey program began in 1964 and has expanded to a variety of surveys addressing the needs of transfusion services, blood centers and physician office laboratories. Its role has evolved from a purely voluntary educational tool for self-improvement to fulfilling the regulatory requirement of CLIA '88. Its educational component will persist through an ungraded technical portion in association with a supplemental questionnaire and a survey critique. PMID- 8436937 TI - For legal reasons. PMID- 8436938 TI - Information processing and gene expression. AB - The process by which information is transferred from DNA to RNA to protein accommodates the further editing and altering of information, particularly in messenger RNA. From one gene, a cell may derive different protein products by altering the information content of mRNA to accommodate the very specialized functions of the cell. Information processing in the form of posttranscriptional RNA processing allows for incredible complexity and differentiation of tissue and tissue function. Most importantly, the posttranscriptional processing of mRNA does not alter the indelible information stored in the DNA which must be maintained and passed on from one generation to the next. Rather, the alteration of information occurs during the transient flow of information from DNA to RNA at the level of messenger RNA. Developmental and differentiation processes are dependent on this information processing which endows the cell with another level of control in gene expression. PMID- 8436939 TI - Medical records and legal liability. PMID- 8436940 TI - Health care reform. PMID- 8436941 TI - The wasted mind syndrome. PMID- 8436942 TI - A lingering elevation of Cai accompanies inhibition of inositol 1,4,5 trisphosphate-induced Ca release in Limulus ventral photoreceptors. AB - Injection of inositol 1,4,5 trisphosphate (InsP3) into Limulus ventral photoreceptors causes an elevation of intracellular free Ca concentration (Cai) and depolarizes the photoreceptors. When measured with the photoprotein aequorin, the InsP3-induced Cai increase follows the time course of depolarization and declines within 1-2 s. However, sensitivity to further injections of InsP3 remains suppressed for several tens of seconds. The possibility that the suppression of Ca release (feedback inhibition) is due to a small lingering elevation of Cai, below the existing detection limit of aequorin, was investigated by measuring Cai with Ca-sensitive electrodes. Double-barreled, Ca selective microelectrodes were used to pressure inject InsP3 and measure Cai at the same point. Light or InsP3 injections into the light-sensitive compartment depolarized the photoreceptors and induced an elevation of Cai that persisted for tens of seconds. Injections of InsP3 during the decay of Cai showed that sensitivity to InsP3 recovered as resting Cai approached the prestimulus level. The relationship between elevated Cai and feedback inhibition was very steep. An elevation of Cai of 1 microM or more was associated with inhibitions of 79 +/- 12.4% (SEM; n = 7) for the InsP3-induced Cai increase and of 76 +/- 8% for depolarizations. With a residual Cai elevation of 0.01 microM or less, the mean inhibition was 10 +/- 7.4% for InsP3-induced Cai increase and 6.6 +/- 4% for InsP3-induced depolarization. Injections of InsP3 into a light-insensitive compartment within the cell induced elevations of Cai with no associated depolarizations or feedback inhibition. To verify that a sustained elevation of Cai is necessary for inhibition of InsP3-induced Cai increase and depolarization, we injected ethyleneglycol-bis-(beta-aminoethylether)-N,N'-tetraacetic acid (EGTA) between two injections of InsP3. Injection of 1 mM EGTA or the related Ca chelator BAPTA, delivered 750 ms after the first injection of InsP3, restored the peak depolarization caused by the second injection of InsP3 to > 80 +/- 3% of control, compared with 13 +/- 8% without an intervening injection of EGTA. Measurement of Cai with aequorin showed that an intervening injection of EGTA partially restored the InsP3-induced Cai increase. The results suggest that feedback inhibition of InsP3-induced Cai increase and depolarization is mediated by a lingering elevation of Cai and not by depletion of intracellular Ca stores. PMID- 8436943 TI - Maltoporins and maltose-binding proteins of Yersinia enterocolitica. AB - Two components of the Yersinia enterocolitica maltose transport system, maltoporin (OmpM) and an osmotically shockable periplasmic maltose-binding protein (MBP) were identified. The synthesis of OmpM (apparent Mr 43,000) and transport of maltose into cells of Y. enterocolitica were induced by maltose and maltodextrins. A mutant lacking OmpM was drastically impaired in maltose transport, independent of induction by maltose. The MBP of Y. enterocolitica (apparent Mr 40,000) was found in the osmotic shock fluid. Its synthesis was induced by maltose. Moreover, rabbit antibodies raised against the MBP of E. coli cross-reacted with the analogous protein from Y. enterocolitica. The MBP of Y. enterocolitica restored the maltose transport activities in delta malE mutant cells of E. coli. PMID- 8436944 TI - Sulphonate utilization by enteric bacteria. AB - A variety of sulphonates were tested for their ability to serve as nutrients for Escherichia coli, Enterobacter aerogenes and Serratia marcescens. Cysteate, taurine and isethionate could not serve as sole sources of carbon and energy but, under aerobic conditions, could be utilized as sources of sulphur. Both sulphate and sulphonate supported equivalent cell yields, but the generation times varied with the sulphonate being metabolized. The sulphonate-S of HEPES buffer, dodecane sulphonate and methane sulphonate was also utilized by some strains, whereas the sulphonate-S of taurocholate was not. None of the sulphonates tested served as a sulphur source for growth under anaerobic conditions. Sulphonate utilization appears to be a constitutive trait; surprisingly, however, cells of E. coli and Ent. aerogenes utilized sulphate-S in preference to that of sulphonate, when both were present. E. coli mutants unable to use sulphate as a source of sulphur because of deficiencies in sulphate permease, ATP sulphurylase, adenylylsulphate kinase (APS kinase) or glutaredoxin and thioredoxin were able to utilize sulphonates; hence sulphate is not an obligatory intermediate in sulphonate utilization. However, mutants deficient in sulphite reductase were unable to utilize sulphonates; therefore, this enzyme must be involved in sulphonate utilization, though it is not yet known whether it acts upon the sulphonates themselves or upon the inorganic sulphite derived from them. PMID- 8436945 TI - Purification and characterization of phosphoenolpyruvate carboxykinase,a catabolic CO2-fixing enzyme, from Anaerobiospirillum succiniciproducens. AB - Phosphoenolpyruvate (PEP) carboxykinase (EC 4.1.1.49) from the obligate anaerobe Anaerobiospirillum succiniciproducens was purified 18-fold. The enzyme was monomeric, with an Mr of 57,000 +/- 2,000. The enzyme was oxygen stable, had a pH optimum of 6.7-7.1, and was stable from pH 5.0 to 9.0. The enzyme displayed Michaelis-Menten kinetics for the substrate PEP and the cosubstrates bicarbonate and ADP with a Km of 0.54 mM, 17 mM and 0.42 mM, respectively. The enzyme required Mn(2+) or Co(2+) in addition to Mg(2+) to exhibit maximum activity. p Chloromercuribenzoate inhibited activity and phosphoenolpyruvate protected the enzyme against inactivation, suggesting that an essential cysteine may be in the active site. PMID- 8436946 TI - A comparison of the amino acid sequence of the serine protease of the fish pathogen Aeromonas salmonicida subsp. salmonicida with those of other subtilisin type enzymes relative to their substrate-binding sites. AB - The amino acid sequence of the so-called 70 kDa (actually 64 kDa) serine protease secreted by the Gram-negative fish pathogen Aeromonas salmonicida has been determined. It shows a high degree of homology with the complete sequence of other bacterial serine proteases which, with molecular masses of approximately 30 kDa, are less than half its size. This homology is particularly marked in regions adjacent to the catalytic triad Asp32, His64 and Ser221 of subtilisin BPN'. Significant features of the A. salmonicida enzyme, a new member of the group of cysteine-containing subtilisin-type serine proteases, are the presence of six cysteine residues in the mature enzyme, a 37 amino acid extension at the N terminus and 215 amino acids at the C-terminus when compared with subtilisin BPN'. In addition to a number of smaller peptide insertions there is a non aligned 32 amino acid sequence in a position corresponding to its introduction between Lys213 and Tyr214 of subtilisin BPN'. This sequence is highly hydrophilic, with Asp/Asn accounting for 10 of the 32 amino acids. Further, the possession of two Cys residues separated by 24 amino acids provides the capacity for stabilizing the peptide as an externalized loop. PMID- 8436947 TI - Molecular analysis and expression of the lipase of Staphylococcus epidermidis. AB - Lipase of Staphylococcus epidermidis 9 was purified from culture supernatant fluid. Two polypeptides (51 and 43 kDa) were detected by SDS-PAGE, of which the 43 kDa polypeptide reacted with anti-lipase serum. The S. epidermidis 9 lipase gene (gehC) was cloned in Escherichia coli and localized to a 2.1 kb sequence by subcloning and transposon mutagenesis. The nucleotide sequence of gehC (2064 nucleotides) was determined and the predicted amino acid sequence of the encoded lipase (77 kDa) identified. A 97 kDa lipase was detected in extracts of E. coli harbouring gehC and in post-exponential-phase culture supernatant fluids of S. epidermidis 9. Data presented indicate that the lipase behaves anomalously during SDS-PAGE and that a pro-lipase is proteolytically processed in cultures of S. epidermidis 9 during growth. PMID- 8436948 TI - Physiological characterization of natural transformation in Acinetobacter calcoaceticus. AB - Acinetobacter calcoaceticus BD413 develops competence for natural transformation immediately after the start of the exponential growth-phase and remains competent up to e few hours into the stationary phase, after which competence gradually declines. The transformation frequencies obtained strongly depend on the kind of transforming DNA and the incubation time with DNA. Up to 25% of the cells in a culture can be transformed. DNA uptake in Acinetobacter does not display sequence specificity, is Mg(2+)-, Mn(2+)- or Ca(2+)-dependent and is uncoupler sensitive. The transforming DNA enters the cells in single-stranded form. These properties constitute a unique combination, not previously observed in other bacteria, and make A. caloaceticus ideally suited for detailed studies of the bioenergetics of DNA translocation. PMID- 8436949 TI - Gene sequence and properties of CelI, a family E endoglucanase from Clostridium thermocellum. AB - The Clostridium thermocellum celI gene, coding for endoglucanase I (CelI), consists of an open reading frame (ORF) of 2640 nucleotides and codes for a protein of M(r) 98531. The ORF was confirmed as celI by comparing the N-terminal sequence of purified recombinant CelI with that deduced from the nucleotide sequence. CelI hydrolysed lichenan and carboxymethylcellulose, but was principally active against barley beta-glucan. It exhibited significant sequence identity with subfamily E2 endoglucanases, and by analogy with others in this group contains a catalytic domain of around 500 residues located in the N terminal half of the protein. The C-terminal region of CelI was highly homologous with the cellulose-binding domain of the non-catalytic cellulosome subunit, S1. A repeated segment, previously shown to be highly conserved in xylanase Z and in other endoglucanases from C. thermocellum, was absent from CelI. Antiserum raised against purified recombinant CelI cross-reacted with proteins contained in the cellulosomes of two strains of C. thermocellu, suggesting that CelI is either a component of the cellulosome or is homologous to other cellulosome proteins. A second gene, located upstream of celI, consisted of an ORF of 1671 nucleotides, coding for a protein of M(r) 61042. Based on its homology with the Escherichia coli tar gene product, the polypeptide encoded by the second gene is tentatively identified as a sensory transducer. PMID- 8436950 TI - An exo-beta-(1,3)-glucanase of Candida albicans: purification of the enzyme and molecular cloning of the gene. AB - A nucleotide sequence encoding an exo-beta-(1,3)-glucanase was cloned from a library of genomic DNA of Candida albicans ATCC 10261. The sequenced gene encodes a protein of 438 amino acid residues. The amino terminal and an internal peptide sequence of the enzyme matched with deduced sequences within the cloned gene. Analysis of the sequence indicated that the nascent protein is processed during secretion by the signal peptidase and a Kex2-like proteinase, yielding a predicted mature enzyme of 400 residues. There is 58% identity and 85% similarity between the amino acid sequences of this exoglucanase and the homologous enzyme of Saccharomyces cerevisiae. An antiserum to the purified exoglucanase cross reacted with the S. cerevisiae exoglucanase and a similar protein secreted by other C. albicans strains and Candida species. There are no sites for N-linked glycosylation in the sequence and this is consistent with the carbohydrate content of the secreted enzyme. Putative upstream promoter elements are associated with the gene. Southern analysis of the gene indicated that it was present at one copy per genome and that the diploid genome of C. albicans ATCC 10261 is heterozygous at this locus for a BglII RFLP. A 2.5 kb mRNA transcript was detected by Northern analysis and gene expression, as monitored by Northern and Western blots, reflected the growth rates of the cultures. PMID- 8436951 TI - Cloning and sequencing of two Candida parapsilosis genes encoding acid proteases. AB - Candida parapsilosis secretes an inducible acid protease (ACP) when cultivated in the presence of bovine serum albumin as the sole nitrogen source. In order to clone the ACP gene (ACP) of C. parapsilosis, a genomic library was screened with C. tropicalis ACP as the probe. Two different ORFs, ACPR and ACPL, were found to hybridize with the C. tropicalis ACP. ACPR contained a DNA sequence in agreement with the N-terminal amino acid sequence of C. parapsilosis ACP isolated from culture supernatants. ACPR was shown to be expressed and functional in a C. tropicalis acid protease mutant (acp) and with SDS-PAGE the protein product showed the same mobility as the ACP secreted by C. parapsilosis. These results imply that ACPR encodes the C. parapsilosis ACP. The deduced amino acid sequence of ACPR is similar to the amino acid sequence of proteases of the pepsin family. As in the case of the C. tropicalis and C. albicans ACP, the 5' extremity of ACPR revealed a propeptide containing two Lys-Arg amino acid pairs that have been identified as peptidase processing sites in several yeast-secreted peptides and protein precursors. As judged from the deduced amino acid sequences, the ACPL product would be similar to that of ACPR; however, a protein corresponding to ACPL was not found in supernatants from C. parapsilosis liquid cultures. In addition, ACPL did not complement the C. tropicalis acp mutant. We conclude that ACPL is a pseudogene or serves an as yet unidentified function. PMID- 8436952 TI - Expression of Bacillus subtilis neutral protease gene (nprE) in Saccharomyces cerevisiae. AB - Expression in the yeast Saccharomyces cerevisiae of the intact nprE gene of Bacillus subtilis, which encodes the pre-pro-NprE neutral protease precursor, resulted in intracellular accumulation of unprocessed precursor without detectable secretion or processing of the expressed gene product. When sequences specifying the signal peptide of yeast invertase were fused upstream of sequences encoding the mature NprE enzyme, nprE gene products were secreted into the culture medium. The secreted protein products were, however, highly, glycosylated and biologically inactive. PMID- 8436953 TI - The glpP and glpF genes of the glycerol regulon in Bacillus subtilis. AB - The Bacillus subtilis glpPFKD region contains genes essential for growth on glycerol or glycerol 3-phosphate (G3P). The nucleotide sequence of glpP encoding a regulatory protein and the previously unidentified glpF encoding the glycerol uptake facilitator was determined. glpF is located immediately upstream of glpK and the two genes were shown to constitute one operon which is transcribed separately from glpP. A sigma A-type promoter and the transcriptional start point for glpFK were identified. In the 5' untranslated leader sequence (UTL) of glpFK mRNA a conserved inverted repeat is found. The repeat is believed to be involved in the control of expression of glpFK by termination/antitermination of transcription, a control mechanism previously suggested for the regulation of glpD encoding G3P dehydrogenase. Expression of glpFK and glpD requires the inducer G3P and the glpP gene product. A 2.9 kb B. subtilis chromosomal DNA fragment containing the glpP open reading frame was cloned to give plasmid pLUM7. pLUM7 contains a functional glpP gene as shown by its ability to complement various glpP mutants. Immediately upstream of glpP an open reading frame is found (ORF1). Disrupting ORF1 by plasmid integration in the B. subtilis chromosome does not affect the ability to grow on glycerol as sole carbon and energy source. With the present report all B. subtilis glp genes located at 75 degrees on the chromosomal map have been identified. PMID- 8436954 TI - DNA sequence of the murE-murD region of Bacillus subtilis 168. AB - The sequence of a 4.4 kbp region of DNA from Bacillus subtilis 168, lying between sporulation genes spoVD and spoVE, has been determined as part of the B. subtilis genomic sequencing programme. The region contains three genes with high sequence similarity to the murE, mraY and murD genes of Escherichia coli. The products of these genes are likely to catalyse various steps in the formation of the precursors for peptidoglycan synthesis in B. subtilis. The regions at 133 degrees on the standard genetic map of the B. subtilis chromosome, and in the 2 min region of the E. coli genetic map, are now shown to contain a large cluster of functionally related genes. Although the linear order of the genes in the cluster is conserved, three genes that are present in the E. coli chromosome, and which are likely to be essential for peptidoglycan synthesis in both organisms, are absent from this region of the B. subtilis chromosome. In general, the B. subtilis cluster differs from that of E. coli in having more extensive intergenic regions, with less potential for translational coupling. PMID- 8436955 TI - Effect of reducing brain glutamine synthesis on metabolic symptoms of hepatic encephalopathy. AB - Liver failure, or shunting of intestinal blood around the liver, results in hyperammonemia and cerebral dysfunction. Recently it was shown that ammonia caused some of the metabolic signs of hepatic encephalopathy only after it was metabolized by glutamine synthetase in the brain. In the present study, small doses of methionine sulfoximine, an inhibitor of cerebral glutamine synthetase, were given to rats either at the time of portacaval shunting or 3-4 weeks later. The effects on several characteristic cerebral metabolic abnormalities produced by portacaval shunting were measured 1-3 days after injection of the inhibitor. All untreated portacaval-shunted rats had elevated plasma and brain ammonia concentrations, increased brain glutamine and tryptophan content, decreased brain glucose consumption, and increased permeability of the blood-brain barrier to tryptophan. All treated rats had high ammonia concentrations, but the brain glutamine content was normal, indicating inhibition of glutamine synthesis. One day after shunting and methionine sulfoximine administration, glucose consumption, tryptophan transport, and tryptophan brain content remained near control values. In the 3-4-week-shunted rats, which were studied 1-3 days after methionine sulfoximine administration, the effect was less pronounced. Brain glucose consumption and tryptophan content were partially normalized, but tryptophan transport was unaffected. The results agree with our earlier conclusion that glutamine synthesis is an essential step in the development of cerebral metabolic abnormalities in hyperammonemic states. PMID- 8436956 TI - Specific in vitro biological activity of snake venom myotoxins. AB - Some snake venoms contain toxins that are reported to be selective for damaging muscle. This specificity can be used to design experiments intended to eliminate muscle. We studied the small myotoxins and fractions IV and V of Bothrops nummifer venom to evaluate their direct effect on cultured muscle cells, neurons, macrophages, and a fibroblast cell line. The small myotoxins, at 100 micrograms/ml for 2 h, had no effect in vitro, contrary to the in vivo applications. Fractions IV and V were both myotoxic and, at 100 micrograms/ml, destroyed all cell types. However, at 10 micrograms/ml the effects of fraction IV were more selective for muscle. Vacuolation of the sarcoplasmic reticulum and T tubules was first seen in the poisoned muscles, without initial lesions in the nuclei, sarcolemma, mitochondria, and rough endoplasmic reticulum. Fractions IV and V have different toxic activity in cells other than muscles and are a mixture of two basic proteins (i and ii). Protein ii is predominant in fraction IV and protein i is predominant in fraction V. The toxic effects may be mediated by the formation of nonspecific ionic pores in the sarcolemma and/or T-tubule muscle membrane. PMID- 8436957 TI - Dopamine D1 agonist SKF 38393 increases the state of phosphorylation of ARPP-21 in substantia nigra. AB - ARPP-21 is a cyclic AMP-regulated phosphoprotein (M(r) = 21,000) that has a distribution in brain similar to that of DARPP-32 (dopamine- and cyclic AMP regulated phosphoprotein, M(r) = 32,000). It is enriched in the medium-sized spiny neurons in the striatum and in the striatonigral nerve terminals in the pars reticulata of the substantia nigra. The present study shows that dopamine D1 agonist SKF 38393 increases the state of phosphorylation of ARPP-21 by 26% in nigral slices and that pretreatment of the slices with D1 antagonist SCH 23390 blocks this effect. These results demonstrate that ARPP-21 is a dopamine regulated phosphoprotein. Because D1 receptors are localized on nerve terminals of striatonigral pathway, the phosphorylation of ARPP-21 is likely to mediate some of the intracellular effects of dopamine on these terminals. PMID- 8436958 TI - Structure of the rat aromatic L-amino acid decarboxylase gene: evidence for an alternative promoter usage. AB - Aromatic L-amino acid decarboxylase catalyzes the biosynthesis of the neurotransmitters dopamine and serotonin. This enzyme is also expressed in nonneuronal tissues. Two reported cDNA sequences show that the pheochromocytoma message differs from the liver message only at the 5' untranslated region. We present the complete exonal organization and promoter sequences of the rat gene encoding this enzyme. The rat aromatic L-amino acid decarboxylase gene is composed of two promoters and 16 exons spanning more than 80 kb in the genome. The first exon carries the majority of the 5' untranslated sequence of the liver cDNA, and the second exon carries that of the pheochromocytoma cDNA. In the third exon, there are two alternatively utilized splicing acceptors specific to the first and second exons. Therefore, both alternative promoter usage and alternative splicing are operative for the differential expression of this gene. The sequence of each promoter region shows putative binding sites for octamer factors and AP-2. PMID- 8436959 TI - Effect of alpha-latrotoxin on acetylcholine release and intracellular Ca2+ concentration in synaptosomes: Na(+)-dependent and Na(+)-independent components. AB - We studied the effect of alpha-latrotoxin (alpha LTX) on [14C]acetylcholine ([14C]ACh) release, intracellular Ca2+ concentration ([Ca2+]i). plasma membrane potential, and high-affinity choline uptake of synaptosomes isolated from guinea pig cortex. alpha LTX (10(-10)-10(-8) M) caused an elevation of the [Ca2+]i as detected by Fura 2 fluorescence and evoked [14C]ACh efflux. Two components in the action of the toxin were distinguished: one that required the presence of Na+ in the external medium and another that did not Displacement of Na+ by sucrose or N methylglucamine in the medium considerably decreased the elevation of [Ca2+]i and [14C]ACh release by alpha LTX. The Na(+)-dependent component of the alpha LTX action was obvious in the inhibition of the high-affinity choline uptake of synaptosomes. Some of the toxin action on both [Ca2+]i and [14C]ACh release remained in the absence of Na+. Both the Na(+)-dependent and the Na(+) independent components of the alpha LTX-evoked [14C]ACh release partly required the presence of either Mg2+ or Ca2+. The nonneurotransmitter [14C]choline was released along with [14C]ACh, but this release did not depend on the presence of either Na+ or Ca2+, indicating nonspecific leakage through the plasma membrane. We conclude that there are two factors in the release of ACh from synaptosomes caused by the toxin: (1) cation-dependent ACh release, which is related to (a) Na(+)-dependent divalent cation entry and (b) Na(+)-independent divalent cation entry, and (2) non-specific Na(+)- and divalent cation-independent leakage. PMID- 8436960 TI - Glial and neuronal marker proteins in the silicone chamber model for nerve regeneration. AB - In the present study, neuronal and Schwann cell marker proteins were used to biochemically characterize the spatiotemporal progress of degeneration/regeneration in the silicone chamber model for nerve regeneration. Rat sciatic nerves were transected and the proximal and distal stumps were inserted into a bridging silicone chamber with a 10-mm interstump gap. Using dot immunobinding assays, S-100 protein and neuronal intermediate filament polypeptides were measured in different parts of the nerve 0-30 days after transection. In the most proximal nerve segment, all the measured proteins were transiently increased. In the proximal and distal stumps adjacent to the transection, the studied proteins were decreased indicating degeneration of the nerve. Within the silicone chamber, the regenerating nerve expressed the Schwann cell S-100 protein already at 7 days, whereas the neurofilament polypeptides appeared later. These observations are corroborated by previous morphological studies. The biochemical method described provides a new and fast approach to the study of nerve regeneration. PMID- 8436961 TI - Neurosecretory vesicles contain soluble and membrane-associated monofunctional and bifunctional peptidylglycine alpha-amidating monooxygenase proteins. AB - Peptidylglycine alpha-amidating monooxygenase (PAM) catalyzes the COOH-terminal amidation of neuropeptides in a reaction requiring the sequential action of two enzymes contained within this bifunctional protein. The CNS contains primarily transcripts encoding rPAM-1 and rPAM-2, integral membrane proteins differing by the presence or absence of a noncatalytic domain separating the two enzymes. Subcellular fractionation of adult rat hypothalamus and hippocampus demonstrated the localization of both enzymatic activities to fractions enriched in neurosecretory vesicles. Upon separation of the soluble contents from the membranes of neurosecretory vesicles, 30-40% of both enzymatic activities was recovered in the soluble fraction. Over 40% of both enzymatic activities remained membrane-associated following removal of peripheral membrane proteins. Antisera specific to different regions of PAM were used to identify intact rPAM-1 and rPAM 2, a monofunctional integral membrane peptidyl-alpha-hydroxy-glycine alpha amidating lyase protein generated from rPAM-1, and a noncatalytic COOH-terminal fragment as the major PAM proteins in carbonate-washed membranes. Endoproteolytic processing generated large amounts of soluble, monofunctional forms of both enzymes from rPAM-1 and smaller amounts of a soluble, bifunctional PAM protein from rPAM-2. A significant amount of both monofunctional enzymes lacking the transmembrane domain was tightly associated with membranes. Whereas soluble mono- and bifunctional enzymes may be released upon exocytosis of neurosecretory vesicles, membrane-associated PAM proteins may remain on the cell surface or be internalized. PMID- 8436962 TI - Arachidonic acid turnover and phospholipase A2 activity in neuronal growth cones. AB - We analyzed de novo synthesis and local turnover of phospholipids in the growing neuron and the isolated nerve growth cone. The metabolism of phosphatidylinositol (PI) was studied with regard to the incorporation of saturated and unsaturated fatty acids and inositol. A comparison of de novo phospholipid synthesis in the intact neuron (whole brain, cell cultures) versus local turnover in isolated growth cone particles (GCPs) from fetal rat brain revealed different incorporation patterns and, in particular, high arachidonic acid (AA) turnover in PI of GCPs. These observations, together with elevated levels of free AA (2.5% of total AA content) in GCPs, demonstrate the predominance of acylation/deacylation in the sn-2 position of PI. GCP phospholipase A2 (PLA2) activity was demonstrated using [3H]-or [14C]AA-phosphatidylcholine (PC) or -PI as the substrate in vitro and GCPs or a cytosolic GCP extract as the source of enzyme. In contrast to PC, which is hydrolyzed very slowly, PI is a very good GCP PLA2 substrate. PLA2 activity is much higher in GCPs than that of phospholipase C, as demonstrated by the comparison of AA and inositol turnover, by the low levels of 1,2 diacylglycerol generated by GCPs, and by the resistance of AA release to treatment of GCPs with RHC-80267, a specific inhibitor of diacylglycerol lipase. The predominance of PLA2 activity in GCPs raises questions regarding its regulation and the functional roles of PI metabolites, especially lysocompounds, in growth cones. PMID- 8436963 TI - Elevated phosphatidyl-CMP is not the source of diacylglycerol accumulation induced by lithium in NG108-15 cells. AB - Previous studies have shown that in the neuroblastoma x glioma hybrid cell line NG108-15 lithium is able to induce an increase in diacylglycerol levels. This effect was shown to be enhanced by the presence of bradykinin. Another striking effect of lithium was a marked gain in the level of the liponucleotide phosphatidyl-CMP. Increased phosphatidyl-CMP levels were detected in the presence of lithium alone but were considerably more pronounced in the presence of both lithium and bradykinin. These results are consistent with the inhibitory action of lithium on key enzymes of the degradation pathway of inositol phosphates, resulting in a decrease in cellular inositol content and in an elevation in levels of phosphorylated inositols. Comparison of the mass of the inositol phosphates and diacylglycerol showed that the lithium-induced diacylglycerol levels were substantially greater than would be expected from phosphoinositide hydrolysis alone. One possible reason for the increase in the level of diacylglycerol through the action of lithium is the reversal of the reaction for the formation of phosphatidyl-CMP. The resulting phosphatidic acid would then need to be further dephosphorylated to diacylglycerol. The lithium-induced elevation of phosphatidyl-CMP was prevented by addition of myo-inositol (10-30 mM), suggesting that the increase in liponucleotide level was due to depletion of cellular inositol. Under the same conditions the elevated diacylglycerol concentration remained unchanged. Consequently, phosphatidyl-CMP is not its source, and diacylglycerol may arise through an effect of lithium on the degradation of phospholipids other than phosphoinositides. The action of phospholipase C or D on phosphatidylcholine is the most likely mechanism. PMID- 8436964 TI - Diminished functional activity of newly synthesized muscarinic acetylcholine receptors in stably transfected Y1 adrenal cells. AB - We have examined the functional responsiveness of newly synthesized m2 muscarinic acetylcholine receptors in stably transfected Y1 adrenal cells. After inactivation of preexisting receptors with the covalent alkylating antagonist propylbenzilylcholine mustard, the number of cell surface receptors returned to control values over a 3-h period. After a 3-h recovery, the cells exhibited diminished sensitivity for muscarinic receptor-mediated inhibition of adenylyl cyclase activity, with much higher concentrations of agonist being required to elicit a response. The functional sensitivity returned to control values over a 12-18-h period. The decreased functional activity was not due to a decreased affinity of the newly synthesized receptors for agonist or to a decrease in the levels of inhibitory G proteins in the cells. The results suggest that muscarinic receptors may be synthesized in a form with diminished functional activity. The ability to study the maturation of receptor function in a transfected cell system should allow a combination of biochemical and molecular genetic approaches to analyze the synthesis and functional responsiveness of muscarinic receptors. PMID- 8436965 TI - Long-term opiate exposure leads to increase in synapsin I in rat spinal cord dorsal root ganglion cocultures. AB - Cocultures of spinal cord and dorsal root ganglion cells contain relatively high concentrations of kappa-opiate receptors. We have previously shown that acute kappa-opiate agonist treatment reduces phosphorylation of synapsin I stimulated by depolarizing agents (such as 60 mM KCl). Here we show that prolonged opiate treatment increases the levels of synapsin I immunoreactivity in the cells. Several opiate agonists, such as U50488, ethylketocyclazocine, dynorphin, and [D Ala2,D-Leu5]enkephalin, caused a 3.0-3.4-fold increase in the immunoreactive level of synapsin I. The effect of the kappa-agonist U50488 on the up-regulation of synapsin I was dose dependent and was blocked by the kappa-opiate antagonist norbinaltor-phimine. The results suggest that continued activation of opiate receptors by chronic agonist treatment up-regulates the levels of synapsin I. This increase in synapsin I could contribute to the development of tolerance to opiates. PMID- 8436966 TI - Cocaine regulation of brain preprothyrotropin-releasing hormone mRNA. AB - Clinical and preclinical evidence supports a possible role for thyrotropin releasing hormone (TRH) in cocaine action. However, the interaction between cocaine and TRH has not been directly examined. In the following report we describe a solution hybridization RNase protection assay that can sensitively detect mRNA for the TRH precursor, prepro-TRH (ppTRH). Using this assay, we examined ppTRH mRNA levels in rat brain regions implicated in cocaine reinforcement, including the nucleus accumbens, hypothalamus, amygdala, hippocampus, and thalamus. Acute cocaine treatment (15 mg/kg) resulted in significant decreases in ppTRH mRNA levels in the amygdala and hippocampus, but not in the hypothalamus, nucleus accumbens, or thalamus, 45 min postinjection. Chronic cocaine treatment (15 mg/kg twice daily for 14 days) resulted in marked regulation in all regions but the thalamus. Regulation was strongly dependent on the length of cocaine withdrawal and persisted up to 72 h postinjection in the amygdala. These studies support the hypothesis that TRH or other ppTRH-derived peptides are involved in cocaine action, especially in the extrahypothalamic regions of the amygdala and hippocampus. PMID- 8436967 TI - Nerve regeneration occurs in the absence of apolipoprotein E in mice. AB - The concentration of apolipoprotein E (apoE), a high-affinity ligand for the low density lipoprotein receptor, increases dramatically in peripheral nerve following injury. This endoneurial apoE is thought to play an important role in the redistribution of lipids from the degenerating axonal and myelin membranes to the regenerating axons and myelin sheaths. The importance of apoE in nerve repair was examined using mutant mice that lack apoE. We show that at 2 and 4 weeks following sciatic nerve crush, regenerating nerves in apoE-deficient mice were morphologically similar to regenerating nerves in control animals, indicating that apoE is not essential for peripheral nerve repair. Moreover, cholesterol synthesis was reduced in regenerating nerves of apoE-deficient mice as much as in regenerating nerves of control animals. These results suggest that the intraneural conservation and reutilization of cholesterol following nerve injury do not require apoE. PMID- 8436968 TI - Stable expression and regulation of a rat brain K+ channel. AB - The Shaw-type K+ channel Kv3.1 was stably transfected in human embryonic kidney cells. Voltage dependence of activation, K+ permeability, sensitivity to external tetraethylammonium, and unitary conductance were similar to Kv3.1 channels expressed transiently in Xenopus oocytes. Kv3.1 channels appear to be regulated because the protein kinase C activator phorbol 12,13-dibutyrate decreased Kv3.1 currents. Based on these results, we find that the stable expression of voltage gated K+ channels in human embryonic kidney cells appears to be well suited for analysis of both biophysical and biochemical regulatory processes. PMID- 8436969 TI - The protooncogene bcl-2 inhibits apoptosis in PC12 cells. AB - During development, many neuronal populations undergo a process of normal, programmed cell death, or apoptosis. Trophic factors regulate this process, but the mechanism by which they suppress apoptosis remains unclear. In the immune system, recent studies have implicated the protooncogene bcl-2 in the lymphocyte survival response to growth factors. To determine whether a similar survival pathway exists in a neuroendocrine cell type, we have expressed bcl-2 in the rat pheochromocytoma PC12 cell line and found that it abrogates the requirement for stimulation by growth factors to survive. bcl-2 expression also substantially delays the onset of injury by the calcium ionophore A23187. PMID- 8436970 TI - Peptidases, peptides, and the mammalian blood-brain barrier. PMID- 8436971 TI - Structures of dopamine receptors. PMID- 8436972 TI - Measurement of hippocampal levels of cellular second messengers following in situ freezing. AB - The in situ freezing technique has been widely used to fix labile metabolites and cellular second messengers in cerebral cortex. In this study, we isolated specific brain regions at 0 degree C from coronal sections of frozen heads following in situ brain freezing and measured regional concentrations of labile metabolites and cellular messengers. These levels in the cortex were compared with those in cortical punches obtained at freezing temperature (less than -40 degrees C) from the same in situ frozen brains and those of cortex dissected from decapitated animals. In both isoflurane- and pentobarbital-anesthetized animals, we observed that the levels of lactate, free fatty acids, inositol 1,4,5 trisphosphate, and diacylglycerol, as well as the proportion of protein kinase C associated with the membrane fraction, were similar in cortical punches taken at freezing temperature and those dissected at 0 degree C. However, with animals decapitated at room temperature, cortical and hippocampal levels of lactate, free fatty acids, and inositol 1,4,5-trisphosphate and the proportion of membrane protein kinase C were significantly higher than those of corresponding brain regions isolated at 0 degree C from in situ frozen brains (p < 0.05). These results indicate that dissection of cortex and hippocampus at 0 degree C following in situ freezing will eliminate decapitation-induced production of artifacts and changes in the levels of cellular second messengers such as inositol 1,4,5-trisphosphate, diacylglycerol, and protein kinase C. The present technique, used in conjunction with in situ freezing, will fix cellular second messengers and labile metabolites in several regions of brain and may facilitate accurate characterization of molecular and cellular mechanisms underlying CNS function. PMID- 8436973 TI - Prolactin-stimulated mitogenesis of cultured astrocytes is mediated by a protein kinase C-dependent mechanism. AB - Prolactin (PRL) has been reported to activate cellular proliferation in nonreproductive tissue, such as liver, spleen, and thymus. Recently, we have extended the possible role of PRL as a mammalian mitogen by demonstrating a mitogenic effect of PRL in cultured astrocytes. Although the cellular mechanisms by which PRL regulates cell growth are not fully understood, protein kinase C (PKC) has been implicated as one of the transmembrane signaling systems involved in the regulation of PRL-induced cell proliferation in Nb2 lymphoma cells and liver. In the present studies, we examined the possible role of PKC in PRL induced proliferation of cultured astrocytes. Incubation of cultured astrocytes with 1 nM PRL resulted in a rapid translocation of PKC from the cytosol to the membrane, with maximal PKC activity in the membrane occurring 30 min after exposure to PRL. Translocation of PKC activity occurred over a physiological range of PRL, with maximal PKC activation occurring at 1 nM. At concentrations greater than 10 nM PRL, there was a decrease in the amount of PKC activity associated with the membrane fraction compared with that of cells stimulated with 1 nM PRL. Incubation of astrocytes with PRL in the presence of the PKC inhibitors staurosporine, 1-(-5-isoquinolinesulfonyl)-2-methylpiperazine, or polymyxin B blocked the PRL-induced increase in cell number with IC50 values of approximately 2 nM, 10 microM, and 6 microM, respectively. PKC is the only known cellular receptor for 12-O-tetradecanoylphorbol 13-acetate (TPA), which stimulates the translocation of PKC from the cytosol to the membrane.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8436974 TI - Calcium buffering and free Ca2+ in rat brain synaptosomes. AB - The effects of K+ depolarization and of stimulation by veratridine on apparent cytosolic free Ca2+ ([Ca2+]cyt) and net Ca2+ accumulation were measured in isolated rat brain presynaptic nerve terminals (synaptosomes). [Ca2+]cyt was determined with fura-2, and Ca2+ accumulation was measured with tracer 45Ca. [Ca2+]cyt was approximately 325 nM in synaptosomes incubated in the normal physiological salt solution under resting conditions. When [K+]o was increased from the normal 5 mM to 30 or 50 mM, 45Ca uptake and [Ca2+]cyt both increased within 1 s. Both increases were directly related to [Ca2+]o for [Ca2+]o = 0.02 1.2 mM; however, the increase in 45Ca uptake greatly exceeded the increase in [Ca2+]cyt. With small Ca2+ loads (< or = 100 mumol/L of cell water, equivalent to the Ca2+ entry during a train of < or = 60 impulses), the 45Ca uptake exceeded the increase in [Ca2+]cyt by a factor of nearly 1,000. This indicates that approximately 99.9% of the entering Ca2+ was buffered and/or sequestered within approximately 1 s. With larger Ca2+ loads, a larger fraction of the entering Ca2+ was buffered; approximately 99.97% of the load was buffered with loads of 250-425 mumol/L of cell water. The ratio between the total Ca2+ entry and the increase in [Ca2+]cyt, the "calcium buffer ratio," beta, was therefore approximately 3,500:1. This ratio was somewhat lower than the ratio of total intraterminal calcium: [Ca2+]cyt, which ranged between approximately 7,300:1 and 12,800:1. When the synaptosomes were activated with 10 microM veratridine ([Ca2+]o = 0.2-0.6 mM), 45Ca influx and [Ca2+]cyt increased progressively for approximately 10 s (beta = 2,700:1-3,050:1) and then leveled off.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8436975 TI - The synaptic vesicle-associated G protein o-rab3 is expressed in subpopulations of neurons. AB - The distribution of o-rab3--a synaptic vesicle-associated low-molecular-weight GTP-binding protein--was studied in various neural tissues of the electric ray Torpedo marmorata. o-rab3 was shown to be associated selectively with isolated cholinergic synaptic vesicles derived from the electric organ. Gel filtration of cholinergic synaptic vesicles using Sephacryl S-1000 column chromatography demonstrated a copurification of o-rab3 with the synaptic vesicle content marker ATP and with SV2--a synaptic vesicle transmembrane glycoprotein. Indirect immunofluorescence using antibodies against o-rab3 and SV2 and a double labeling protocol revealed an identical distribution of both antigens in the cholinergic nerve terminals within the electric organ and at neuromuscular junctions. An immunoelectron microscopic analysis demonstrated the presence of o-rab3 at the surface of the synaptic vesicle membrane. In the CNS immunofluorescence of o-rab3 and SV2 overlap only in small and distinct areas. Whereas SV2 has an overall only in small and distinct areas. Whereas SV2 has an overall distribution in nerve terminals of the entire CNS, o-rab3 is restricted to a subpopulation of nerve terminals in the dorsolateral neuropile of the rhombencephalon and in the dorsal horn of the spinal cord. Our results demonstrate that the synaptic vesicle associated G protein o-rab3 is specifically expressed only in subpopulations of neurons in the Torpedo CNS. PMID- 8436976 TI - Enhancement of the synthesis and secretion of nerve growth factor in primary cultures of glial cells by proteases: a possible involvement of thrombin. AB - Newborn rat brain astrocytes cultured in vitro in a chemically defined medium are shown to secrete enhanced levels of nerve growth factor (NGF) when they are exposed to various types of proteases. Proteolytic enzymes such as alpha-thrombin or collagenase induce a continuous, dose-dependent enhancement of the levels of cell-secreted NGF. Incubation of astrocytes for a 24-h period with 300 ng/ml of alpha-thrombin (approximately 9 nM, or 1 U/ml) results in an increase of the levels of cell-secreted NGF by a factor of three- to fourfold, and at doses 10 times higher, stimulation by a factor of up to four- to fivefold was observed. This phenomenon reflects an enhancement of the cellular pool of NGF mRNA, already noticeable after 3 h of treatment, which is preceded by a temporary activation of protooncogenes encoding transcription factors of the AP-1 family, such as c-fos, c-jun or junB. Trypsin, plasmin, alpha-chymotrypsin, or elastase also enhanced, to different extents, the levels of cell-secreted NGF. However, unlike alpha thrombin or collagenase, these enzymes cause, above a critical concentration, an extensive cell detachment from the solid support, and this is accompanied by a decrease of their activity on the production of NGF, so that their dose-response curves are bell shaped. Stimulation was maximal at those concentrations that cause a limited loosening of the cell-substratum interactions, as evidenced by a retraction of some cell processes after 24 h of treatment. Studies of the effect of alpha-thrombin indicate that the proteolytic activity itself is required to enhance the production of NGF by astrocytes. Inactivation of alpha-thrombin with D-phenyl-alanyl-L-propyl-L-arginine chloromethyl ketone, phenylmethylsulfonyl fluoride, antithrombin III, or hirudin results in a marked decrease of the stimulatory effect. Furthermore, the prolonged presence of alpha-thrombin is required to elicit a maximal effect on the levels of extracellular NGF, which was observed after 48 h of treatment. It is known that some effects of alpha-thrombin require binding to the cell surface. We found that gamma-thrombin, which still has some proteolytic activity but has lost its ability to bind to the cell surface, is almost as potent as alpha-thrombin in promoting the release of NGF. It is concluded that the effect of thrombin on NGF synthesis is essentially mediated by its proteolytic activity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8436977 TI - Expression of glia maturation factor beta mRNA and protein in rat organs and cells. AB - Rat glia maturation factor beta (GMF-beta) cDNA was obtained by reverse transcription of rat brain mRNA followed by polymerase chain reaction amplification, using primers from the human sequence. The deduced amino acid sequence of rat GMF-beta differed from the human counterpart in only three places: His27 in place of Asn, Val51 in place of Ile, and Leu93 in place of Val. The high degree of evolutionary conservation suggests that GMF-beta plays an essential role in animal cell physiology. The expression of GMF-beta mRNA in the rat was studied by the northern blot technique, using a rat cRNA probe corresponding to the entire coding region. GMF-beta mRNA was predominantly expressed in the brain and spinal cord, although trace levels were found in other organs, including testis and ovary. In the brain GMF-beta mRNA was detectable at as early as embryonic day 10, and persisted through as late as postnatal month 14, with minor variations in between. On the other hand, GMF-beta protein exhibited more obvious developmental changes, with its level increasing slowly prenatally and plateauing at 1 week after birth. GMF-beta mRNA and protein were also observed in several cultured cells. Some cells of neural origin contained higher levels of GMF-beta protein compared with cells derived from other sources. Through demonstration of mRNA and confirmation by immunoblotting, we conclude that GMF-beta is synthesized by rat organs and that GMF-beta is predominantly a brain protein. PMID- 8436979 TI - Glucose utilization rates in single neurons and neuropil determined by injecting nontracer amounts of 2-deoxyglucose. AB - A nontracer amount of 2-deoxyglucose (DG) was intravenously injected into rats, which were frozen 2 and 4 min later in liquid nitrogen. The freeze-dried samples of cell bodies of anterior horn cells, dorsal root ganglion cells, and cerebellar Purkinje cells, as well as the neuropil adjacent to anterior horn cell bodies, were prepared. Their contents of glucose, glucose 6-phosphate, DG, and 2 deoxyglucose 6-phosphate were microassayed using an enzymatic amplification reaction. NADP cycling. Based on the resulting data and theoretical equations previously described, glucose utilization rate (GUR) and apparent distribution volumes (DVs) of glucose and DG were determined. Anterior horn cell bodies had the highest GUR and their neuropil the lowest, although apparent DVs of glucose and DG were similar in both. This indicates that the glucose supply was equally balanced in all, but that the cell bodies had higher functional activity supported by hexokinase (and other enzymes) related to their energy demands. Dorsal root ganglion cells showed the lowest 2-deoxyglucose 6-phosphate formation rate, but their GUR was slightly higher than that of neuropil because of their markedly large DV of glucose, thus demonstrating that the abundant glucose supply supports the neuronal function. Purkinje cells indicated GUR and apparent DVs similar to molecular and granular layers. PMID- 8436978 TI - Labelling of 5-hydroxytryptamine3 receptors with a novel 5-HT3 receptor ligand, [3H]RS-42358-197. AB - RS-42358-197[(S)-N-(1-azabicyclo[2.2.2]oct-3-yl)-2,4,5,6-tetrahydro-1 H benzo[de]isoquinolin-1-one hydrochloride] displaced the prototypic 5 hydroxytryptamine3 (5-HT3) receptor ligand [3H]quipazine in rat cerebral cortical membranes with an affinity (pKi) of 9.8 +/- 0.1, while having weak affinity (pKi < 6.0) in 23 other receptor binding assays. [3H]RS-42358-197 was then utilized to label 5-HT3 receptors in a variety of tissues. [3H]RS-42358-197 labelled high affinity and saturable binding sites in membranes from rat cortex, NG108-15 cells, and rabbit ileal myenteric plexus with affinities (KD) of 0.12 +/- 0.01, 0.20 +/- 0.01, and 0.10 +/- 0.01 nM and densities (Bmax) of 16.0 +/- 2.0, 660 +/- 74, and 88 +/- 12 fmol/mg of protein, respectively. The density of sites labelled in each of these tissues with [3H]RS-42358-197 was similar to that labelled with [3H]GR 65630, but was significantly less than that found with [3H]-quipazine. The binding of [3H]RS-42358-197 had a pharmacological profile similar to that of [3H]quipazine, as indicated by the rank order of displacement potencies: RS-42358 197 > (S)-zacopride > tropisetron > (R)-zacopride > ondansetron > MDL72222 > 5 HT. However, differences in 5-HT3 receptors of different tissues and species were detected on the basis of statistically significant differences in the affinities of phenylbiguanide, and 1-(m-chlorophenyl)biguanide when displacing [3H]RS-42358 197 binding. [3H]RS-42358-197 also labelled a population (Bmax = 91 +/- 17 fmol/mg of protein) of binding sites in guinea pig myenteric plexus membranes, with lower affinity (KD = 1.6 +/- 0.3 nM) than those in the other preparations. Moreover, the rank order of displacement potencies of 15 5-HT3 receptor ligands in guinea pig ileum was found not to be identical to that in other tissues. Binding studies carried out with [3H]RS-42358-197 have detected differences in 5 HT3 receptor binding sites in tissues of different species and further underscore the unique nature of the guinea pig 5-HT3 receptor. PMID- 8436980 TI - Parallel up-regulation of catecholamine biosynthetic enzymes by dexamethasone in PC12 cells. AB - We sought to investigate whether dexamethasone produces a coordinated, time dependent effect on all enzymes in the catecholamine biosynthetic pathway in PC12 cells. The levels of mRNAs of tyrosine hydroxylase (TH), aromatic L-amino acid decarboxylase (AADC), and dopamine beta-hydroxylase (DBH) were examined at 0, 6, 12, 24, and 48 h after dexamethasone (5 microM) treatment to PC12 cells. The levels of all enzyme mRNAs steadily increased for 24 h, although the increase of AADC mRNA content was slow. The increased mRNA levels of TH and AADC were maintained at 48 h, whereas the level of DBH mRNA was sharply decreased at 48 h. The maximally induced mRNA levels were approximately 5.0-, 2.4-, and 7.0-fold higher than the control levels of TH, AADC, and DBH, respectively. The elevation of enzyme activities was detected later than the increase in levels of mRNAs. The maximal activities of TH, AADC, and DBH were reached between 48 and 72 h with 3.6 , 1.8-, and 8.0-fold increases, respectively. Low, but detectable, phenylethanolamine N-methyltransferase (PNMT) activity was observed in PC12 cells, and dexamethasone increased its activity 5.6-fold at 72 h. The PNMT mRNA was easily detected by northern blot analysis after exposure for 24 h to dexamethasone. The data suggest that, in PC12 cells, dexamethasone up-regulates all catecholamine biosynthetic enzyme genes in a parallel fashion. PMID- 8436981 TI - Neurite outgrowth and protein phosphorylation in chick embryonic sensory ganglia induced by a brief exposure to 12-O-tetradecanoylphorbol 13-acetate. AB - An exposure to 12-O-tetradecanoylphorbol 13-acetate (TPA) at 20 nM for as short as 30 min was sufficient to elicit neurite outgrowth from explanted chick embryonic sensory ganglia. Attachment of the ganglia to the collagen-coated substratum during exposure to TPA was essential for subsequent neurite outgrowth. Pulse-labeling with [35S]-methionine indicated no significant difference in protein synthesis between control and TPA-treated ganglia. In vitro phosphorylation assay revealed a prominent protein kinase C substrate with an apparent molecular mass of 66,000 dalton (66 kDa) in chick embryo ganglia extracts. Treatment of intact ganglia with TPA for 30 min also specifically stimulated the phosphorylation of the same protein. When staurosporine, a potent inhibitor of protein kinase C, was present during TPA treatment, both neurite outgrowth and the phosphorylation of the 66-kDa protein were blocked. Biochemical analysis of the phosphorylated 66-kDa protein indicated that (1) phosphorylation was only in serine residue, (2) the pI value was 4.5, (3) after V8 protease digestion, two phosphorylated peptide fragments, 6.0 and 7.5 kDa in size, were produced, and (4) it cross-reacted with an antiserum raised against a 66-kDa neurofilament subunit from rat spinal cord. These results suggest that early activation of protein kinase C and the phosphorylation of the 66-kDa protein may be involved in neuritogenesis. PMID- 8436982 TI - Transcriptional organization of a Drosophila glutamic acid decarboxylase gene. AB - We previously described the sequence and expression pattern of a Drosophila mRMA (Gad) that encodes the major soluble form of glutamic acid decarboxylase (GAD). We now report the transcriptional organization of the Drosophila Gad gene. Based on a combination of DNA sequence, RNase protection, primer extension, and polymerase chain reaction analyses, we conclude that the transcription unit for a 3.1-kb Gad mRNA is composed of eight exons that span approximately 17-kb genomic interval. By this analysis, the site of Gad transcript initiation overlaps with a recognition sequence that confers binding of the zeste transcription factor to other promoter elements. We emphasize that our analysis of the Gad transcription unit provides no evidence for alternative RNA splicing as a mechanism for the generation of GAD isoforms. Thus, the several GAD-immunoreactive proteins (putative GAD isoforms) that can be detected in Drosophila extracts are probably encoded by distinct genes. PMID- 8436983 TI - Solubilization and biochemical characterization of the melatonin deacetylase from Xenopus laevis retina. AB - Melatonin deacetylase, an enzyme activity recently discovered in the Xenopus laevis retina, regulates local melatonin levels. The deacetylase occurs in retina, retinal pigment epithelium, and skin, all sites of melatonin action, and is widely distributed among vertebrates. We have solubilized the enzyme from Xenopus retina and pigment epithelium using nonionic detergents, and have developed a specific enzyme assay. We have characterized the enzyme and now report that the deacetylase is relatively specific for melatonin and is inhibited by the melatonin precursor N-acetylserotonin and the product of the deacetylase, 5-methoxytryptamine. Inhibition of deacetylase activity by eserine (physostigmine) suggests a relationship between deacetylase and cholinesterase activities. However, among a variety of cholinesterase inhibitors tested, only eserine inhibits the deacetylase. Furthermore, eserine is much less potent as an inhibitor of the deacetylase than the cholinesterases, and purified cholinesterases failed to deacetylate melatonin. We also show that melatonin deacetylase and aryl acylamidase (an enzyme related to cholinesterases) activities are differentially extractable from Xenopus ocular tissues, and that they exhibit different pH optima and inhibition profiles. Our results provide an initial characterization of the Xenopus retinal melatonin deacetylase, and indicate that deacetylase activity is distinct from cholinesterase and aryl acylamidase activities. PMID- 8436984 TI - Uncemented total hip arthroplasty in patients with aseptic necrosis of the femoral head and previous bone grafting. AB - Tibial strut bone grafting and more recently fibular strut grating (vascularized) have been used in the treatment of aseptic necrosis of the femoral head. The authors evaluated the technical aspects and results of uncemented total hip arthroplasty after previous tibial bone grafting of the femoral head in patients with aseptic necrosis. Review of postoperative radiographs demonstrated that residual tibial graft prevented optimal femoral canal fit and positioning of the prosthetic stem in 10 of 13 hips (in the coronal plane). In the nine hips with a minimum 2-year follow-up period, two required revision for loosening of the femoral component. The authors recommend that, when performing an uncemented total hip arthroplasty in patients with previous strut grafting, special attention be directed to adequate graft removal, particularly in the lateral greater trochanteric fossa to prevent varus placement of the femoral component. An intraoperative anteroposterior radiograph with the final femoral broach in place may be useful in verifying adequate strut graft removal and optimal canal fill with proper prosthesis positioning. PMID- 8436985 TI - Femoral component offset. Its effect on strain in bone-cement. AB - The magnitude of the offset of the femoral prosthesis strongly influences the mechanics of the hip following a total hip arthroplasty. An increased offset increases the moment arm of the abductor muscles. This reduces the abductor force required for normal gait and, consequently, reduces the resultant force across the hip joint. These factors are advantageous. However, increased offset also increases the bending moment on the implant, which could adversely increase the strain in the medial cement mantle. To evaluate the relative advantages and disadvantages of these conflicting results of increasing the offset of the femoral component the authors measured in vitro in cadaver femora the effect of differing offsets of the femoral component on strain in the cement mantle. After testing the intact femora, the authors cemented femoral prostheses in place and quantified the abductor force, resultant force, and strain in the cement mantle under loading conditions simulating single limb stance at different femoral offset levels. The reduction in both abductor and resultant force was substantial with increased femoral component offset, but the strain in the cement of the proximal medial portion of the cement mantle was not significantly increased. PMID- 8436986 TI - Five to eight year results of the Johnson-Elloy (Accord) total knee arthroplasty. AB - Between February 1982 and December 1985, 133 knees in 107 patients were replaced with a cemented Johnson-Elloy (Accord) total knee arthroplasty. Thirty-five knees were lost during the follow-up period because of death in 29, revision in 3, infection in 1, and refusal of follow-up evaluation in 2. The results of the remaining 98 knees in 76 patients with a 5-8 year follow-up period are presented. The procedure was carried out in all cases presenting for surgery, irrespective of pathology and degree of deformity. The range of flexion achieved as a mean of 93.5 degrees in the osteoarthritic group and 100 degrees in the rheumatoid arthritic group. Eighty-seven percent of the osteoarthritic group and 95% of the rheumatoid arthritic group achieved between 10 degrees and 50 degrees of rotation at 90 degrees of flexion, which was maintained for the duration of the study. Adequate stability in both groups, valgus-varus and rotation in extension, and anteroposterior in flexion was achieved. Survivorship was 97.7% at 80 months. PMID- 8436987 TI - The contribution of the nonporous distal stem to the stability of proximally porous-coated canine femoral components. AB - The contribution of the distal nonporous-coated stem to the stability of the uncemented femoral components, which were porous coated only proximally, was investigated under two conditions: (1) immediately after insertion and (2) at 6 months, 1 year, and 2 years after surgery in a canine model. The relative motion of the femoral components at the bone porous-coating interface under loads simulating the canine midstance was measured at these time periods using displacement transducers. The measurements were repeated after severing the connection between the porous-coated proximal body and the nonporous-coated distal stem through a small hole in the anterior cortex. The results showed that while the distal nonporous-coated stem enhanced the immediate stability of the proximally porous-coated uncemented femoral components, it contributed little to the long-term stability of the femoral components after bony ingrowth had occurred in vivo. The mean relative motion between the body of the prosthesis and the cortical bone increased from 12 microns (+/- 7 microns) to 31 microns (+/- 34 microns) in the posterior transverse direction when the stem was immediately severed after the surgery. However, at 6 months, 1 year, and 2 years after surgery, extensive bone ingrowth had occurred into the proximal porous-coated regions of the body and provided excellent stability to the femoral components. With bone ingrowth, the mean relative motion was less than 5 microns at any site. Under these conditions, severing the stem did not increase the relative motion of the prostheses significantly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8436988 TI - Intramedullary versus extramedullary tibial alignment systems in total knee arthroplasty. AB - One hundred twenty consecutive total knee arthroplasties were performed to compare the accuracy of intramedullary versus extramedullary tibial resection guides. An intramedullary guide (group 1) was used in 60 cases and an extramedullary guide (group 2) was used in another 60 cases. In group 2, the distal portion of the extramedullary guide was shifted 3 mm medial to the midpoint of the ankle in order to position it over the center of the talus. Postoperative tibial component alignment angles were similar in both groups (group 1, 0.43 degrees varus; group 2, 0.36 degrees valgus). However, 88% of tibial components in group 2 were aligned within 2 degrees of the 90 degrees goal versus only 72% of tibial components in group 1. Satisfactory alignment can be obtained with either intramedullary or extramedullary resection guides, although a wider range of error was encountered with intramedullary guide use. Distal positioning of the extramedullary guide over the center of the talus rather than the midpoint of the ankle is important to avoid varus tibial resection. Extramedullary guides avoid the potential complications of intramedullary guide use, including fat embolization and hypoxia, intraoperative fracture, loss of polymethyl methacrylate pressurization, and inability of intramedullary rod passage due to deformity, retained hardware, or pathologic bone disease. PMID- 8436989 TI - Treatment of nonunions about the knee utilizing custom total knee arthroplasty with press-fit intramedullary stems. AB - Juxta-articular nonunion about the knee is infrequent but may be a troublesome problem, especially if it is about a total knee arthroplasty or associated with an arthritic joint. This technique of total knee arthroplasty with an uncemented press-fit intramedullary rod and bone grafting achieved union in all nine nonunions about the knee. Radiographic review indicated all nonunions to be healed by an average of 2 months, with none taking longer than 6 months to heal. The average postoperative Hospital for Special Surgery knee score was 78 (range, 50-91), with 4 excellent, 4 good, and 1 poor result. This study demonstrated that this is a successful salvage procedure for juxta-articular nonunions in the face of either arthritis in the adjacent joint, severe articular incongruency, or an ipsilateral total knee arthroplasty. PMID- 8436990 TI - The effectiveness of intermittent plantar venous compression in prevention of deep venous thrombosis after total hip arthroplasty. AB - The purpose of this study was to investigate the effectiveness of intermittent pneumatic compression of the plantar venous plexus with the newly developed arteriovenous impulse system. Seventy-four patients about to undergo primary unilateral total hip arthroplasty for osteoarthrosis, all receiving a standard thrombosis prophylaxis regime of thigh-length anti-embolic stockings, 5,000 IU heparin delivered subcutaneously twice daily, and 400 mg hydroxychloroquine sulfate delivered twice daily, were entered in a prospective trial. The patients were allocated at random to also receive the arteriovenous impulse system on the foot of the operated side. On approximately postoperative day 12 bilateral ascending venography was performed. There were 44 patients in the nonpumped group and 30 patients in the pumped group. The incidence of deep venous thrombosis was 6.6% in the pumped group and 27.27% in the nonpumped group. The incidence of thrombosis was significantly lower in the pumped group (P < .025). The authors conclude that chemical prophylaxis plus the use of the mechanical, pneumatic, and arteriovenous impulse system reduces the incidence of thromboembolic complications further than chemical prophylaxis alone. PMID- 8436991 TI - Screw and cement fixation of large defects in total knee arthroplasty. A sequel. PMID- 8436992 TI - Effects of femoral component material properties on cementless fixation in total hip arthroplasty. A comparison study between carbon composite, titanium alloy, and stainless steel. AB - Carbon-fiber-reinforced-carbon composite material is an attractive implant material because its modulus of elasticity can be made similar to that of cortical bone. This study investigated the effect of femoral prosthesis elastic modulus on cementless implant fixation. Distal, as well as proximal, relative micromovements between implant and bone were measured in two testing protocols (axial-load and torsional-load), comparing identically shaped carbon composite (modulus of elasticity = 18.6 GPa), Ti6Al4V (100 GPa), and 630 stainless steel (200 GPa) prostheses. In the axial-load test, proximal mediolateral micromotions were significantly larger in the flexible composite stem than in the two metals. In the torsional-load test, rotational micromotions and "slop" displacements in the flexible stem were significantly larger proximally and significantly smaller distally than in the two metals. While these results suggest that proximal stress transfer may be improved by a flexible stem, they raise the possibility of increased proximal micromotion, and suggest that improved proximal fixation may be necessary to achieve clinical success with flexible composite femoral components. PMID- 8436993 TI - Mechanical compatibility of noncemented hip prostheses with the human femur. AB - It is generally accepted that more flexible implants are needed to reduce stress shielding and postoperative thigh pain. However, there is no detailed information on the stiffness of currently used implants relative to the human femur. The purpose of this study was to determine the stiffness characteristics (bending, torsional, and axial) of human femora relative to commercially available prostheses as a first step in assessing the mechanical compatibility of the implants. This was achieved by computerized tomography scanning of a collection of human femora from proximal to distal at 10 mm intervals, digitizing the cross sectional contours, and calculating the stiffness characteristics of each section using standard beam theory. The results show that significant stiffness mismatches exist, especially for larger stem sizes and for stems fabricated from cobalt-chrome alloy. Interestingly, certain implant stiffness values are lower than those of the femur for stems up to 15 mm in diameter, substantially so if the implant is made from titanium alloy and incorporates design features that reduce area and moments of inertia. The data suggest that only larger implant sizes need to be adjusted for increased flexibility compared with current stands. PMID- 8436994 TI - Accurate preparation of the patella during total knee arthroplasty. AB - The development of a resection guide that facilitates accurate preparation of the patella during total knee arthroplasty is reported. Use of the guide prevents tilting of the prosthesis, as well as over or underresection of the patella. PMID- 8436995 TI - Fixation of cemented acetabular prostheses. The influence of preoperative diagnosis. AB - The authors evaluated the fixation of cemented acetabular prostheses in patients with osteoarthritis (20 hips), rheumatoid arthritis (15 hips), and sequelae after fracture of the femoral neck (13 hips) using roentgen stereophotogrammetric analysis. The three-dimensional displacements of the cups were measured during the first 2 postoperative years, and radiographs were examined to assess bone quality, containment, inclination, and area of cement surrounding the cups. There was a greater proportion of migrating cups in patients with rheumatoid arthritis and fracture of the femoral neck compared with osteoarthritis. Patients with poor bone quality according to the modified Engh index, small cement area surrounding the cups, and cups with small inclination displayed increased frequency of migration. PMID- 8436996 TI - Loosening of a femoral stem associated with the use of an extended-lip acetabular cup liner. A case report. AB - A case of femoral component loosening secondary to impingement on an extended-lip acetabular cup liner is presented. This impingement led to the accelerated creation of particulate polyethylene wear debris. The particulate polyethylene induced an osteolytic response about the femoral component, which contributed to the failure of this component. It is recommended that intraoperative examination for impingement, especially in extension, be performed when using liners of this design. PMID- 8436997 TI - Fabellar impingement in total knee arthroplasty. A case report. AB - Fabellar impingement can cause postoperative pain, swelling, and catching, and can significantly compromise the results of total knee arthroplasty. The appearance of a large fabella on preoperative radiographs should raise suspicion about possible impingement. Impingement against the femoral or tibial component of the prosthesis should be assessed by inspection and palpation during trial reduction. The fabella can be removed via the anterior approach prior to component fixation, although it tends to be firmly embedded in the lateral head of the gastrocnemius tendon and requires careful dissection. A separate posterolateral approach will most likely be needed to accomplish complete fabellar excision after the components are secured. PMID- 8436998 TI - Stiff muscles. PMID- 8436999 TI - Tonic clonic status epilepticus. PMID- 8437000 TI - Short-term cognitive changes after unilateral temporal lobectomy or unilateral amygdalo-hippocampectomy for the relief of temporal lobe epilepsy. AB - Forty two patients who had unilateral temporal lobe surgery (either temporal lobectomy or amygdalo-hippocampectomy) were evaluated using a selection of cognitive tests before and soon after surgery, to examine whether the amygdalo hippocampectomy produces less cognitive impairment than the standard en bloc resection. On specific indices of cognitive functioning an amygdalo hippocampectomy rather than a temporal lobectomy, undertaken on the temporal lobe thought to mediate that particular function, produced less impairment, in terms of change in cognitive function resulting from the operation. An amygdalo hippocampectomy carried out on the temporal lobe not thought to mediate such skills, however, resulted in less improvement or more deterioration in these functions than a temporal lobectomy, except in the case of delayed prose recall, where a right amygdalo-hippocampectomy led to more improvement than a right temporal lobectomy. Overall there were few scores which distinguished between the different surgical procedures for cognitive outcome. PMID- 8437002 TI - Neurological stamp. Hermann Boerhaave 1668-1738. PMID- 8437001 TI - Ictal/postictal SPECT in the pre-surgical localisation of complex partial seizures. AB - Single photon emission computed tomography (SPECT) used in conjunction with HM PAO (Ceretec-Amersham International) was used to image regional cerebral blood flow (rCBF) in 28 patients with medically intractable complex partial seizures during or soon after a seizure, and interictally. Changes from interictal rCBF were seen in 26/28 (93%) patients. The main findings were; 1) During the seizure- hyperperfusion of the whole temporal lobe; 2) Up to 2m postically--hyperperfusion of the hippocampus with hypoperfusion of lateral temporal structures; 3) From 2 15m postically--hypoperfusion of the whole temporal lobe. When compared with EEG and MRI data, correct localisation to one temporal lobe was obtained in 23 patients. In one further patient bilateral temporal foci, and in a further two patients frontal foci, were correctly identified. There were no disagreements between EEG and SPECT localisation. Temporal lobe surgery was successful (by the criterion of at least 90% reduction in seizure frequency) in all but one of the 23 patients operated on. It is concluded that ictal/postictal SPECT is a reliable technique for the presurgical localisation of complex partial seizures. The data indicate a likely sequence of changes in rCBF during and after complex partial seizures of temporal lobe origin. PMID- 8437003 TI - Mortality in patients with epilepsy: a study of patients in long term residential care. AB - The causes of death in a group of patients with severe epilepsy in long term residential care over a period of 11 years were assessed and the standardised mortality rate (SMR) determined. A total of 3392 patient-years were surveyed. One hundred and thirteen deaths were recorded in the period and this represents an overall mortality rate which is almost twice the expected rate for this population (SMR = 1.9; 95% CI 1.6-2.3; p < 0.01). Most deaths were due to cancer (26%), bronchopneumonia (25%), circulatory diseases (24%), were seizure-related (12%) or due to sudden unexpected death (6%). The highest SMRs in the neoplasm sub-group were due to cancers of the pancreas (SMR = 6.2) and hepatobiliary tumours (SMR = 17.6). Twenty per cent of patients died of epilepsy or epilepsy related causes (that is accidents, during seizures, status or sudden unexpected death). One in every 480 patients died due to a sudden unexpected death. This study in a highly selected population seems to confirm suggestions that mortality rates are higher in patients with epilepsy than in the general population, but prospective studies are warranted to ascertain underlying mechanisms. PMID- 8437004 TI - Conventional and quantitative EEG in the diagnosis of delirium among the elderly. AB - This study was performed to determine whether an admission quantitative EEG (QEEG) could assist in the differential diagnosis of encephalopathy among a group of elderly subjects with delirium, dementia, and delirium coexistent with dementia. Thirty four subjects from 57 to 93 years had standard 17-channel EEG and quantitative EEG studies, using a linked-ear reference. EEGs were independently rated by two electroencephalographers blind to clinical diagnosis, using conventional criteria to assess the degree of encephalopathy. Brain maps were scored by a scale developed by the authors. Numerical data examined included mean posterior dominant frequency, absolute and relative power in the delta, theta and alpha bands, and slow-wave ratios. The grouping of experimental subjects was by the discharge diagnosis, made using DSM-III-R criteria. Stepwise discriminant analysis was performed to determine which EEG and QEEG variables were best able to distinguish cases. Variables which collectively distinguished normal from encephalopathic records were Mini-Mental State Examination scores and relative power in the alpha frequency band. Variables which collectively distinguished delirium from dementia were EEG theta activity, relative power in delta, and brain map rating. The results suggest that cross-sectional QEEG study is potentially useful in the early differential diagnosis of encephalopathy, and that the variables which distinguish normal from encephalopathic patients might differ from the variables which distinguish delirium from dementia. PMID- 8437005 TI - Three arms: a case study of supernumerary phantom limb after right hemisphere stroke. AB - A case of supernumerary phantom limb is described after a haematoma within the right basal ganglia. The phantom, which persisted for many months, occurred in the context of severe left hemiplegia, sensory loss, hemianopia, and neglect. The subjective reality of this "third arm" caused the patient considerable distress, which was not ameliorated by his attempts to rationalise its existence. Although deeply confused by the phantom, the patient was otherwise fully oriented, with a high verbal IQ, and normal cognition. Two distinct formal interpretations of the phenomenon are discussed. PMID- 8437006 TI - Correlation of interleukin-2 and soluble interleukin-2 receptor with clinical activity of multiple sclerosis. AB - Concentrations of interleukin-2 (IL-2) and soluble IL-2 receptor (sIL-2R) in serum and CSF samples were measured in 63 patients with multiple sclerosis (MS) to evaluate their usefulness as markers of disease activity. CSF concentrations of IL-2 and sIL-2R were significantly higher in MS relapse compared with MS patients in remission or with control subjects. These concentrations correlated with the clinical score by which disease severity was assessed, with the number of relapses per year, and with the total disease duration. Furthermore, there was evidence of intrathecal release of IL-2 and sIL-2R in clinically active MS. The results extend the notion that an activated cellular immune state parallels the evolution of the pathological process in MS and suggest that measurement of IL-2 and sIL-2R concentrations may provide an objective marker of disease activity in patients with MS. PMID- 8437007 TI - Correlations of leuko-araiosis with cerebral atrophy and perfusion in elderly normal subjects and demented patients. AB - CT images of leuko-araiosis in brain slices were quantified according to volumes of reduced Hounsfield units in frontal periventricular white matter in groups of elderly patients with multi-infarct dementia (MID, n = 23) and dementia of the Alzheimer type (DAT, n = 16). Volumes of leuko-araiosis, estimates of atrophic cerebral tissue, and local cerebral perfusion utilising inhalation of xenon gas as the indicator were correlated on the same CT slices. Ratios of frontal leuko araiosis to total brain tissue volume were similar for patients with MID and DAT (mean 5.7 (SD 2.1)% v 6.5 (3.2%)), and both were significantly greater than ratios in elderly normal volunteers (3.1(1.3)%, 0 < 0.001). Cerebral atrophy (measured as the ratio of volumes of cerebrospinal fluid to total brain area) for DAT patients was 17.0 (6.7)%, which was greater than for MID patients (12.5 (5.4)%; p < 0.05) and both types of patients showed more cerebral atrophy than did age matched, elderly normal subjects. Cerebral perfusion was decreased in all regions measured in patients with MID and DAT compared with elderly normal subjects. Multi variate regression analyses correlated frontal leuko-araiosis with reductions of local cerebral blood flow in subcortical grey matter (p < 0.025) in patients with vascular dementia but not in those with DAT. These quantitative measures implicate decreased perfusion due to atherosclerosis in territories supplied by the deep penetrating cerebral arteries in the pathogenesis of leuko-araiosis in patients with vascular dementia, but suggest a different pathogenesis for leuko-araiosis in Alzheimer's disease. PMID- 8437008 TI - CNS aspergillosis in organ transplantation: a clinicopathological study. AB - The clinical characteristics and neuropathological findings of 22 organ transplant recipients with CNS aspergillosis were reviewed. Thirteen patients had liver, six kidney, two heart and one had cluster transplants. The most frequent neurological symptoms were alteration of mental status (86%), seizures (41%) and focal neurological deficits (32%). Meningeal signs were less common (19%). Aspergillus spp invasion of the blood vessels with subsequent ischaemic or haemorrhagic infarcts, and solitary or multiple abscesses were the predominant neuropathological findings. The lungs were the probable portal of entry; however, isolated CNS aspergillosis was seen in two patients. Antemortem diagnosis of the infection was made in half of the patients. Concomitant diabetes mellitus was noted in 59% of the patients and bacterial or other severe infections in 86%. No specific clinical or pathological pattern could be identified among patients with different types of organ transplants. In addition CNS aspergillosis was preceded by organ rejection and the need for intense immunosuppression and retransplantation in the majority of the patients. PMID- 8437009 TI - MRI-pathological correlate of brain lesions in a necropsy case of HTLV-I associated myelopathy. AB - A postmortem case of HTLV-I associated myelopathy (HAM)/tropical spastic paraparesis (TSP) with a history of remission and exacerbation of neurological signs and symptoms, resembling those of multiple sclerosis is reported. MRI analysis revealed lesions in the periventricular white matter in addition to atrophy of the thoracic spinal cord, characteristic of HAM/TSP. The cerebral periventricular areas consisted of ill-defined paucity of myelin sheaths with astrocytic gliosis and hyaline thickening of blood vessels. The poorly demarcated white matter lesions found in both brain and spinal cord were different from plaques found in multiple sclerosis. It is suggested that, in some cases of HAM/TSP, inflammatory lesions that destroy myelin can involve not only the spinal cord but also the cerebral periventricular white matter. PMID- 8437010 TI - A pilot trial of dextromethorphan in amyotrophic lateral sclerosis. AB - Assuming the presence of glutamate-induced neurotoxicity in amyotrophic lateral sclerosis 14 patients were treated with dextromethorphan, an N-methyl-D-aspartate receptor antagonist. The patients were treated with 150 mg dextromethorphan or placebo daily for 12 weeks in a double-blind crossover trial, with a wash out period of 4 weeks between the two treatment periods. Thereafter the surviving patients were treated with 300 mg dextromethorphan daily for up to 6 months in an open trial. No positive effects on clinical or neurophysiological parameters (relative number of axons, and compound muscle action potentials in the abductor digiti minimi muscle) were observed either in the double-blind trial or in the open trial. PMID- 8437011 TI - Miller Fisher syndrome is associated with serum antibodies to GQ1b ganglioside. AB - A recent report described serum anti-GQ1b ganglioside antibodies in Miller Fisher syndrome (MFS), a clinical variant of Guillain-Barre syndrome (GBS). Four consecutive cases of MFS all had high titre anti-GQ1b antibodies which were absent from all control sera including those of patients with GBS. PMID- 8437012 TI - Pineal cysts: an incidental MRI finding? AB - The incidence of pineal cysts (PC) in "standard" MRI was reviewed. Seven cases of PC were found from 400 consecutive MRI examinations. PC did not produce clinically relevant symptoms in any of the patients. Our data, as well as those emerging from a critical review of the literature, suggest that PC are often asymptomatic and represent an incidental MRI finding. PMID- 8437013 TI - "Fou rire prodromique" heralding a brainstem stroke. AB - A patient manifested pathological laughter heralding the onset of brainstem stroke leading to a "locked-in" state. The pathological laughter did not recur. MRI revealed a bilateral ventral pontine infarct. The clinico-anatomical correlations of this rare phenomenon of fou rire prodromique are discussed. PMID- 8437014 TI - Responses to facial and non-facial stimuli presented tachistoscopically in either or both visual fields by patients with the Capgras delusion and paranoid schizophrenics. AB - An experiment was carried out designed primarily to test A B Joseph's suggestion that patients with Capgras delusion may have problems integrating information between the two cortical hemispheres; and at the same time it was meant to examine J Cutting's ideas linking schizophrenia in general, and the Capgras delusion in particular, to right hemisphere dysfunction. Three patients with the Capgras delusion and three matched controls diagnosed as paranoid schizophrenics were briefly presented pairs of line-drawn object and photographs of faces randomly in the left visual field, the right visual field or bilaterally. The results with objects revealed no particular pattern of performance for either group; but, when faces were shown, the controls revealed the usual left visual field/right hemisphere advantage while for the Capgras group this was reversed. The results are not consistent with a simple prediction from Joseph's hypothesis but they are in accord with Cutting's theory-though they also pose some problems for it, which are discussed. PMID- 8437015 TI - Contralateral selective saccadic palsy after a small haematoma in the corona radiata adjacent to the genu of the internal capsule. PMID- 8437016 TI - Magnetic evoked responses elicited in the frontalis muscle. PMID- 8437017 TI - The clinical, genetic and dystrophin characteristics of Becker muscular dystrophy. II. Correlation of phenotype with genetic and protein abnormalities. AB - We have correlated a detailed clinical assessment of 67 patients with proven Becker muscular dystrophy with the results from genetic and protein analyses. There was an overall deletion frequency of 80%, rising to 92.6% in the large group of patients defined on clinical grounds as being of "typically" mild severity. The deletions in this group were all clustered in the region of the gene between exons 45 and 59; the most common deletion was of exons 45-47 and all but one started at exon 45. No similar deletions were seen in the patients with more severe disease, in whom the diverse genetic defects included a duplication and a very large deletion. Dystrophin patterns in the "typical" group were also very characteristic, and in both groups were as predicted from the genetic defect, the size of deletions being inversely proportional to the size of the protein produced. PMID- 8437018 TI - Delayed neurological deterioration following carbon monoxide poisoning: MRI findings. AB - We present two patients with delayed neurological deterioration following apparent recovery from carbon monoxide poisoning in whom magnetic resonance imaging showed abnormalities. In the first patient, cortical grey matter abnormalities were seen without white matter changes. Visual evoked potentials were, however, abnormal. In the second, diffuse white matter lesions were detected. In neither patient were basal ganglia lesions seen. PMID- 8437019 TI - Diminution and enhancement of visuo-spatial neglect with sequential trials. AB - We report three cases of visuo-spatial neglect after unilateral right hemisphere damage. Each patient undertook 100 sequential trials of line bisection. All patients were grossly impaired, placing their transections of the longer lines significantly to the right of true centre. When the trials were analysed in two consecutive halves, one patient showed only minimal differences in accuracy between the two blocks. One patient improved greatly on the second block, and one patient became significantly worse. The results are discussed in terms of differential "learning" and "fatigue" effects, and their clinical significance is outlined. PMID- 8437020 TI - Sydenham chorea: clinical, EEG, MRI and SPECT findings in the early stage of the disease. AB - An 18-year-old man suffered from acute Sydenham chorea appearing coincidently with beta-haemolytic streptococcal throat infection. Imaging techniques documented lesions of basal ganglia and substantia nigra. In the early course of the disease vascular lesions may be important pathogenetic mechanisms of this acquired movement disorder. PMID- 8437021 TI - Are H and stretch reflexes in hemiparesis reproducible and correlated with spasticity? AB - The measurement of spasticity has always presented a problem to clinicians and researchers alike. As yet, there is no literature addressing the reproducibility of the existing barrage of clinical evaluations of spasticity and reflex measurement. Also not clear is whether or not a systematic relationship might exist between these multiple indices of spasticity. After delineating the differences in spasticity scores and reflex functions between spastic and normal states, the aims of this study were to examine the reliability of these measurements in hemiparetic subjects, and the correlation between altered reflex functions and clinically measured spasticity. An aggregate of lower limb reflexes was compared between ten spastic hemiparetic and seven age-matched normal subjects. Lower limb reflexes examined were: (1) the ratio of maximal H reflex to M response (H/M ratio), (2) the inhibition of the H reflex during vibration (Hvib/Hctl ratio), and (3) soleus stretch reflexes (SR/M ratio). H and stretch reflex latencies were shorter (P < 0.05), and reflex amplitudes were significantly greater (H/M ratios, P < 0.05; SR/M areas, P < 0.005) in spastic subjects. While H/M ratios, Hvib/Hctl ratios, SR/M areas and SR onset angles were highly reproducible, only some physiological measurements showed consistent but non-significant relationships with clinical spasticity. The decreased reflex latencies and increased reflex responses in the hemiparetic subjects suggested that spasticity may be related to reduced reflex thresholds. The physiological measurements and clinically assessed tone were both valid and reproducible, indicating that they can be used to evaluate the long-term effects of therapeutic intervention.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437022 TI - Abnormal sympathetic skin response in patients with autoimmune vitiligo and primary autoimmune hypothyroidism. AB - The sympathetic skin response was studied in 21 patients with autoimmune vitiligo or hypothyroidism or both. No response to stimulation was found in 6 patients, but 4 with both diseases showed abnormal results. Sympathetic skin response is useful in evaluating sudomotor activity of the autonomic nervous system, and it is concluded that patients with autoimmune vitiligo, autoimmune hypothyroidism and especially those with both diseases show evidence of sudomotor dysfunction. PMID- 8437023 TI - Segmental hyperhidrosis in syringomyelia with Chiari malformation. AB - Segmental hyperhidrosis was seen in three cases of syringomyelia with Chiari malformation confirmed by magnetic resonance imaging. Using the iodine-starch reaction, all three cases showed hyperhidrosis in the areas roughly corresponding to those of sensory disturbances. Two possible modes of pathogenesis are discussed: stimulation of preganglionic neurons and interference to the inhibitory tract. PMID- 8437024 TI - Presence of T-cell subset abnormalities in newly diagnosed cases of multiple sclerosis and relationship with short-term clinical activity. AB - Abnormalities of T-cell subsets in patients with multiple sclerosis are well known; in order to assess whether immunological abnormalities are relevant in the pathogenesis of the disease after its clinical onset, peripheral blood lymphocyte subsets (CD3+, CD4+, CD4(+)-CD45RA+, CD4+CD45RA-, CD8+, CD8+CD57+, CD57+, CD25+) were analysed serially in 25 patients at the first clinical episode suggestive of inflammatory demyelinating disease and in an equal number of age- and sex-matched controls. During the follow-up period (12-18 months, mean 14) 6 of 25 patients presented new relapses: in this subgroup of patients, significant changes in CD4+ ratio (% CD4+CD45RA-/%CD4+CD45RA+) were detected in comparison both with healthy controls and with clinically stable patients. Patients clinically stable at follow-up did not display immunological abnormalities, regardless of the presence or absence of cerebrospinal fluid and/or magnetic resonance imaging alterations consistent with multiple sclerosis. These findings suggest a possible prognostic role of early T-cell subset imbalance in multiple sclerosis. PMID- 8437025 TI - Favourable outcome in non-traumatic anterior interosseous nerve lesions. AB - Six patients with non-traumatic anterior interosseous nerve palsy are described. In five patients the onset was acute with upper arm pain, which peaked within 4 weeks and thereafter declined. Virtually complete spontaneous recovery occurred in all patients between 9 and 24 months. It is concluded that non-traumatic anterior interosseous nerve lesions are most likely to reflect a circumscribed form of brachial neuritis and that surgical decompression should be deferred for at least a year or indefinitely if recovery is proceeding. PMID- 8437026 TI - Resistance to ischaemic nerve-fibre block in diabetes mellitus and in mitochondrial encephalomyopathies. AB - Thermal thresholds were measured during ischaemic compression block in the left forearms of 26 healthy subjects, 10 patients with diabetes mellitus and 6 patients suffering from different kinds of mitochondrial disorders. Cold and warm thresholds in the 6 patients with deficiencies in the respiratory chain increased earlier than in normals. When cold perception was impaired, cold stimuli were perceived as warmth and pinprick perception attenuated. In diabetics cold thresholds were less elevated during ischaemic block than in controls. This was paralleled by tingling paraesthesiae in all groups. The findings show that higher resistance to ischaemic nerve-fibre block in diabetes mellitus is not exclusively based on increased anaerobic metabolism. PMID- 8437027 TI - The clinical, genetic and dystrophin characteristics of Becker muscular dystrophy. I. Natural history. AB - We have investigated 67 patients with proven Becker muscular dystrophy (BMD) using a standard protocol including a detailed history and a functional and clinical examination. Our aim was to define the natural history of the disease in a large cohort of patients in the light of the diagnostic methods now available. In all patients with or without an X-linked family history, the diagnosis was confirmed by the identification of a deletion or other abnormality in the dystrophin gene, and abnormal dystrophin on immunoblotting and immunocytochemistry of muscle biopsy samples. In graphs of functional and muscle score against age, two groups of patients emerged. In the larger group the disease was milder and patients remained ambulant into their forties or beyond. A smaller group had more severe disease with a slightly earlier onset, much earlier loss of ambulation, more frequent abnormal electrocardiographic findings and much lower reproductive fitness. The relationship of these clinical findings to the genetic and protein abnormalities found in the patients is explored in the accompanying paper. PMID- 8437028 TI - Confidence interval construction for effect measures arising from cluster randomization trials. AB - Methods of confidence interval construction are provided for summary measures of treatment effect arising from designs randomizing clusters to one of two treatment groups. Three basic designs are considered for the case of continuous and dichotomous variables: completely randomized, pair-matched and stratified. PMID- 8437029 TI - Determinants of wound infection in gastrointestinal operations: the Israeli study of surgical infections. AB - Risk factors for wound infection in operations involving the opening of the gastrointestinal (GI) tract, were explored in a prospective study. There were 813 consecutive operations performed during a period of 9-14 months in 11 Israeli hospitals. The total crude infection rate was 21.6%, and the respective rates for operations on the stomach, small bowel and colon were 14.8, 21.4 and 25.4%. Of 17 putative risk factors, the strongest predictor was the performance of 2 or more operations during the same admission. Other significant risk factors were: a diagnosis of intestinal obstruction or perforation, introduction of an open drain, emergency admission, age over 40, hospital stay prior to surgery 7 or more days, urinary catheter and infection on admission. Adjustment for these factors in a logistic regression model reduced the effect of the anatomical site of the operation (i.e. large bowel vs stomach) to a non-significant level. PMID- 8437030 TI - Relationships between change in aerobic fitness and changes in blood pressure and plasma lipids in men and women: the "Adelaide 1000" 4-year follow up. AB - The aim was to assess relationships between increased aerobic fitness sustained over 4 years, and changes in blood pressure (SBP and DBP) and lipids. Measurements were made of BP, lipids, weight, and fitness in 1000 middle-aged men and women entering a fitness programme, and were repeated 2 and 4 years later. The 342 men and women selected for this 4-year follow-up were either consistent fitness "gainers" (improved by > 5%) or "non-gainers" (improved by < or = 5%) at 2 and 4 year stages. For men, comparisons of these groups and multiple regression analyses failed to show significant relationships between changes in fitness and risk factors over the 4 year period. For women, "gainers" improved more than "non gainers" in SBP (by 4 mmHg, p < 0.03), HDL/cholesterol ratio (by 0.01 mmol l-1, p < 0.0001), and triglycerides (by 0.02 mmol l-1, p < 0.05); regression analyses resulted in a significant relationship between changes in fitness and SBP (B = 0.012, p < 0.05). The study gave weak support to the existence of causal relationships between aerobic fitness and CHD risk factors for women, and no support for men. PMID- 8437031 TI - The Physical Activity Scale for the Elderly (PASE): development and evaluation. AB - A Physical Activity Scale for the Elderly (PASE) was evaluated in a sample of community-dwelling, older adults. Respondents were randomly assigned to complete the PASE by mail or telephone before or after a home visit assessment. Item weights for the PASE were derived by regressing a physical activity principal component score on responses to the PASE. The component score was based on 3-day motion sensor counts, a 3-day physical activity dairy and a global activity self assessment. Test-retest reliability, assessed over a 3-7 week interval, was 0.75 (95% CI = 0.69-0.80). Reliability for mail administration (r = 0.84) was higher than for telephone administration (r = 0.68). Construct validity was established by correlating PASE scores with health status and physiologic measures. As hypothesized, PASE scores were positively associated with grip strength (r = 0.37), static balance (r = +0.33), leg strength (r = 0.25) and negatively correlated with resting heart rate (r = -0.13), age (r = -0.34) and perceived health status (r = -0.34); and overall Sickness Impact Profile score (r = -0.42). The PASE is a brief, easily scored, reliable and valid instrument for the assessment of physical activity in epidemiologic studies of older people. PMID- 8437032 TI - Vasectomy and prostate cancer risk: methodological review of the evidence. AB - Two recent studies have reported a significantly elevated risk of prostate cancer among vasectomized men. To assess whether the new results conflict with earlier studies that found no significant overall association, and, if so, whether such a conflict could have a methodological basis, we reviewed the six major epidemiological studies of this topic. Statistical analysis revealed significant (p < 0.01) heterogeneity among the associations in the six studies, attributable to one of the recent studies. Scrutiny of the studies for fulfillment of eight methodological standards for scientific validity revealed that no study completely fulfilled more than four standards, and that all studies were deficient in avoiding detection bias and obtaining accurate vasectomy histories. Our review indicates that the evidence on this topic is indeed conflicting, that the quality of the evidence does not resolve the conflict, and that future studies of this topic, designed to ensure scientific credibility of results, are needed. PMID- 8437033 TI - The reappraisal of the association of glycosylated hemoglobin A1c (HbA1c) and blood pressure: a hypertension and diabetes study in a Taiwan rural area. AB - The association of age, body weight, body mass index (BMI) and glycosylated hemoglobin A1c (HbA1c) to blood pressure in the general population of the Ho-long area in Taiwan was examined. A total of 1341 subjects, 746 men and 595 women, aged 40-90 years, were studied. Sex-specific multiple regression analyses were carried out on variables both univariately and significantly associated with blood pressure. Results show HbA1c to be significantly associated with SBP in both males and females before age, weight and/or BMI are adjusted (p < 0.05). After controlling for these confounders, the strength of SBP-HbA1c association was slightly reduced in males, but remained significant. In contrast, there was no significance in females. Moreover, no significant relationship in DBP-HbA1c was found in either sex group. These findings suggest that although a positive correlation was found between HbA1c and SBP, HbA1c or glucose status appeared to be a less important contributing factor in hypertension than age or body weight. PMID- 8437034 TI - Reliability and validity of interview data on chronic diseases. The Mini-Finland Health Survey. AB - The Mini-Finland Health Survey was designed to obtain a comprehensive picture of health and of the need for care in Finnish adults, and to develop methods for monitoring health in the population as a whole. Out of a nationally representative sample of 8000 people aged 30 or over, 7217 (90%) were both interviewed at home by local public health nurses using simple open-ended questions and, independently of this interview, subsequently examined in a two phase health examination. The estimate of chronic morbidity based on the health interview (56%) was close to the prevalence of definite somatic diseases diagnosed in the health examination (54%), and the agreement between the two methods was moderate (kappa = 0.53). The estimated prevalence of cardiovascular diseases was the same (23%) in the health interview and in the health examination; the agreement was substantial (kappa = 0.74). The prevalence of respiratory and musculoskeletal diseases and mental disorders was underestimated in the interview by 52, 25 and 78%, respectively; the agreement between results of the two methods was relatively low (kappa = 0.43, 0.38 and 0.30, respectively). These results suggest that both the health examination and the health interview methods, as used in this survey, have useful applications in monitoring the population's health. PMID- 8437035 TI - China vignettes: medical homilies from a visiting professor's journal. PMID- 8437036 TI - Life expectancy and mitochondrial DNA. Do we inherit longevity from our mother's mitochondria? PMID- 8437038 TI - Potential effects of non-differential underestimation of exposure. PMID- 8437037 TI - Models for risk of low cholesterol. PMID- 8437039 TI - Rejoinder: chance-corrected sensitivity and specificity for three-zone diagnostic tests. PMID- 8437040 TI - "Work-up bias". PMID- 8437041 TI - Irene Walsh, RN, BSN, MSN, National Medical Care Homecare. PMID- 8437042 TI - Home infusion of intravenous immune globulin in human immunodeficiency virus infected children. AB - Intravenous immune globulin (IVIG) is administered prophylactically to reduce the development of secondary infections in human immunodeficiency virus (HIV) infected children whose helper-inducer T-cell (CD4) lymphocyte count is greater than 200 cells/mm3. By progressively crippling the body's immune system, HIV allows opportunistic infections, which account for approximately 90% of AIDS related deaths, to develop. In a recently published controlled study conducted by the National Institute for Child Health and Development (N Eng J Med 1991:325:73 80), children who received monthly infusions of IVIG experienced significantly more time free of infection. Home administration of IVIG is safe, convenient, and cost-effective. The first dose of IVIG, however, is administered in a hospital or clinic under physician supervision. Mild side effects occur in approximately 3% to 5% of patients; at least 90% of these effects are related to the infusion rate. In this article, a suggested protocol for home administration including commonly reported side effects and precautionary measures of anaphylaxis is presented. PMID- 8437043 TI - Intravenous cyclophosphamide in lupus nephritis. AB - Systemic lupus erythematosus (SLE) is a chronic disorder of the immune system that affects persons of all ages. Figures released by the Lupus Foundation of America, Inc. indicate that approximately 15,000 new cases of SLE are diagnosed each year. This number includes discoid lupus, which is confined to the skin; drug-induced lupus, which manifests SLE-type symptoms that fade when the implicated drug is discontinued; and SLE, which causes inflammation in a number of organs. Of the three types of lupus, only SLE can lead to life-threatening central nervous system and/or renal involvement. By the 1960s, lupus nephritis and progressive renal disease emerged as dominant factors in SLE patient morbidity, and kidney failure had become the most common cause of death. This manifestation is presently treated with intravenous cyclophosphamide, which improves survival and preserves renal function. PMID- 8437044 TI - Stimulating new developments. Colony-stimulating factors. AB - Drug-induced low white-blood-cell counts have long impaired our ability to treat patients. Colony-stimulating factors are now available for intravenous or subcutaneous administration. These glycoproteins act on hematopoietic cells by binding to specific cell surface receptors and by stimulating proliferation, differentiation, commitment, and activation of new white blood cells. A brief overview of patient population, indications, actions, and adverse reactions for hospital or home use is presented. PMID- 8437045 TI - Vascular access devices--management of common complications. AB - Developments in vascular access technology, along with advances in therapy, have created specific challenges for the intravenous nurse caring for patients with indwelling vascular access devices. The nurse clinician must be aware of clinical and technical complications that may occur, as well as the nursing management of those complications. PMID- 8437047 TI - Pathological Society of Great Britain and Ireland. 166th Meeting. London, 6-8 January 1993. Abstracts. PMID- 8437046 TI - Catheter-related colonization associated with percutaneous inserted central catheters. AB - The intravenous therapy team at Massachusetts General Hospital studied the potential infectious risks of maintaining percutaneous inserted central catheters (PICC) for prolonged periods. Cultures of 100 PICC sites and catheters were performed on removal of the catheters, which had remained in place for 2 to 43 days. The insertion sites and/or proximal or distal segments of the catheters were found to be colonized in 11% of the patients, with distal catheter tips significantly colonized in only four patients. Nine of the patients were colonized at the insertion site. Bacteremia did not occur as a result of the extended dwell time of the catheters. PMID- 8437048 TI - Parasites and the behavior of biting flies. AB - Biting fly behavior involved in parasite transmission is reviewed. Except for the areas of activity and probing, few investigations have addressed ways in which parasites might alter vector behavior. Given the manner in which parasites alter behavior in other arthropods (e.g., habitat choice, color preference), it is reasonable to expect infected hematophagous flies to behave differently from uninfected conspecifics. This could have important epidemiological consequences. PMID- 8437049 TI - Helminth parasites of the American avocet Recurvirostra americana (Aves), from the Salt Lake basin, Utah. AB - Five species of cestodes and 1 species of trematode, for a total of 4,770 (chi- =79.5) helminths, were obtained from 60 American avocets, Recurvirostra americana, collected from July to September 1985 and 1986 in the Salt Lake basin, Utah. The most prevalent parasite was the cestode Diplophallus coili (95%). It occurred in mature pairs 90% of the time. All species of helminths showed a contagious distribution except for mature D. coili, which had a uniform distribution. This uniform distribution, which is unusual for species of helminths, has been observed for at least 4 species of large tapeworms in the recurvirostrids. The helminth community consisted of 3 specialists, 1 generalist, and 2 of uncertain status. The same specialists have been reported also in R. americana from Texas, Colorado, and Manitoba, Canada. PMID- 8437050 TI - Parelaphostrongylus tenuis (Nematoda) in white-tailed deer (Odocoileus virginianus) in central Iowa. AB - Heads of hunter-killed white-tailed deer (Odocoileus virginianus) were obtained from a tri-county area in central Iowa in December 1991 and examined for the presence of Parelaphostrongylus tenuis (Dougherty, 1945). Adults of P. tenuis were found in 45% of 42 deer heads; the mean intensity of infection was 3.6 (range: 1-16). Prevalence of infection was significantly greater in female deer > 13 mo of age in comparison to males of similar age (54 vs. 17%). Mean intensity of infection was significantly greater in deer > 13 mo of age than in younger deer (4.4 vs. 1.2 nematodes/head). Both prevalence and intensity of P. tenuis infection in deer in Iowa were comparable to levels reported elsewhere in the United States and Canada. These results further define the distribution of P. tenuis and suggest that susceptible hosts sharing habitat with white-tailed deer in Iowa are at risk of infection with this parasite. PMID- 8437051 TI - Banding patterns of Fasciola hepatica and Fasciola gigantica (Trematoda) by isoelectric focusing. AB - Liver flukes Fasciola hepatica and Fasciola gigantica are polymorphic and vary morphologically depending upon the host being parasitized. It is known also that mixed infection occurs where both species are present. A technique involving protein separation was used to distinguish the 2 species. Isoelectric focusing of soluble proteins was performed on polyacrylamide gels using whole-body proteins from adult flukes. Although many bands appeared common to both species and some were shared with host tissues, the banding patterns could be used to distinguish 1 species from the other. Soluble protein isoelectric focusing is simple, reproducible, and has very good resolution. It seems well suited to the differentiation of the 2 fluke species. PMID- 8437052 TI - Effects of serum from neurocysticercosis patients on the structure and viability of Taenia solium oncospheres. AB - Neurocysticercosis, caused by Taenia solium, is arguably the most common parasitic disease of the central nervous system. In taeniid infections of nonhuman mammals, there is strong evidence of immunity in the intermediate host to the invasive larvae (oncospheres). This immunity, which is mediated by antibody and complement, has been exploited to develop vaccines that effectively prevent infection. To examine the immune response in humans, T. solium eggs were hatched and activated in vitro. Activated oncospheres were incubated with heat inactivated sera from patients with neurocysticercosis with or without complement (guinea pig serum). Controls included oncospheres plus complement alone, normal human serum alone, normal serum with complement, or buffer alone. Serum from infected patients, especially with complement, markedly reduced oncosphere mobility and led to disappearance of secretory vesicles and loss of membrane integrity. Viability as assessed by staining with dimethyl-thiazolyl-diphenyl tetrazolium was reduced from 92.5% in controls to 61.5% with immune serum and 38.8% with immune serum and complement (P < 0.01). Preliminary western blot analysis showed antigens at 22, 64, and 70 kDa recognized by all 3 sera, but not by control sera. These data suggest that sera from patients with cysticercosis can kill oncospheres in vitro and may be used to identify protective antigens. PMID- 8437053 TI - Host utilization by the salmon louse Lepeophtheirus salmonis (Copepoda: Caligidae) in the Sea of Japan. AB - Two species of salmon (masu salmon Oncorhynchus masou and pink salmon O. gorbuscha) captured in the northern Sea of Japan during April 1990 were examined for infection by adult female salmon lice (Lepeophtheirus salmonis) to assess the relative importance of each to the parasite. Masu salmon had relatively low prevalence and abundance of infection and carried less than 4% of the estimated parasite population, indicating that masu salmon are utilized rarely by L. salmonis and may not be important hosts. In contrast, the infection level on pink salmon was higher, with pink salmon carrying more than 96% of the parasites found on the 2 salmon populations. PMID- 8437054 TI - Schistosoma mansoni and Trichobilharzia ocellata: comparison of secreted cercarial eicosanoids. AB - Schistosoma mansoni cercarial transformation and early stages of penetration can be correlated to specific eicosanoid products. Cercarial eicosanoids are suggested to play immunoregulatory roles during penetration. We examined production of cercarial eicosanoids by S. mansoni compared with that of the duck parasite Trichobilharzia ocellata after incubation with linoleate. Secretions were separated by reversed-phase high pressure liquid chromatography and also quantified by radioimmunoassay. The 2 parasites, differing in their immune evasion, synthesized the same types of prostaglandins, leukotrienes, and hydroxy eicosatetranoic acids in similar quantities. Eicosanoid fractions of both species also showed a similar inhibition of superoxide production by human neutrophils. The coincidence of eicosanoid production suggests a function of eicosanoids in processes that are similar in both species. PMID- 8437055 TI - Modification of the ultrastructure of the muscle larva of Trichinella pseudospiralis following exposure to acidified pepsin solution. AB - Examination of the cuticle of Trichinella pseudospiralis by transmission electron microscopy revealed an epicuticle, exocuticle, and mesocuticle, each divided into several layers. The epicuticle consisted of an outermost thin plasmalemmalike infracuticular material covering an inner trilaminar membrane. The exocuticle was granular and could be divided into 2 regions on the basis of density. The mesocuticle was fibrillar and 3 regions could be distinguished based on the orientation of fibrils. The cuticle appears attached to the hypodermis by hemidesmosomes. The infracticular structure was altered following isolation of larvae by pepsin-HCl digestion of host muscle. PMID- 8437056 TI - Bacterial flora, a possible source of serotonin in the intestine of adult female Ascaris suum. AB - The effect of intestinal bacteria on 5-hydroxytryptamine (5-HT, serotonin) level and 5-HT turnover rates in Ascaris suum intestine are presented. Ascaris suum were incubated in media containing antibiotics for 24 hr, and the bacterial flora in the anterior regions of the intestine of A. suum was eliminated. The bacteria were significantly reduced (> 99%) but not eliminated in the middle and posterior segments of the worm. The 5-HT level decreased in the intestine after 24 hr incubation in antibiotics, whereas the 5-HT turnover rate increased (131 ng/mg protein/hr). Two possible sources of 5-HT from the intestine were examined: the intestinal tissue itself and the microflora inhabiting the intestine. The 5-HT level in the microflora was 30% higher (72.6 ng/g) than the intestinal tissue (43.3 ng/g) in control samples (0 hr, no antibiotics). These values decreased significantly after 24 hr incubation in A. suum saline. The 5-HT values decreased to 18.6 ng/g in the presence and 28.6 ng/g in the absence of antibiotics. The 5 HT turnover rate during this time period indicated that as the number of bacteria declined, the 5-HT turnover rate also declined in the microflora, but the 5-HT turnover rate in the intestinal tissues increased. Results from these studies suggest that bacterial 5-HT may be contributing to the 5-HT level in A. suum intestinal tissue. PMID- 8437057 TI - Proteinase activity in miracidia, transformation excretory-secretory products, and primary sporocysts of Schistosoma mansoni. AB - Proteinase activity was detected in the culture medium of transforming miracidia and in detergent extracts of Schistosoma mansoni miracidia and primary sporocysts using a fluorescent substrate, carbobenzoxy-phenylalanyl-arginyl-7-amino-4- trifluoromethylcoumarin. Medium collected after the first 24 hr of miracidial cultivation (transformation medium; TM) contained most (80%) of the activity released during 5 days of in vitro culture. Based on proteinase activity contained in Triton X-100 extracts of whole larvae, miriacidia and primary sporocysts exhibited a similar amount of total activity per organism, whereas specific activity was about 2-fold greater in miracidia. Approximately 10% of total miracidial activity was released during the first 24 hr of transformation. This early release of proteinase is consistent with possible involvement of these enzymes in miracidial snail penetration. Proteinase activities from larval extracts and culture media were identical when characterized for thiol dependence, inhibitor profile, and pH optimum and indicate that the proteinase(s) belongs to the cysteine class of acidic endopeptidases. Further studies with TM revealed a substrate preference for a hydrophobic amino acid in the P2 position. High performance liquid chromatography gel filtration showed 2 peaks of activity at 19,000 and 36,000 Da, whereas specific inhibitor labeling yielded heterogeneous banding in the molecular weight range of 33,000-44,000 Da. Lastly, sporocyst extracts incubated with snail plasma (cell-free hemolymph) revealed degradation of high molecular weight hemolymph proteins, including hemoglobin. The finding of significant cysteine proteinase activity in miracidia and primary sporocysts and the continued low level of secretion by sporocysts suggest a functional role of these proteinases in the establishment and/or maintenance of infections within the snail host. PMID- 8437058 TI - Morphological characterization of adult Echinococcus granulosus as a means of determining transmission patterns. AB - Host induced changes in morphological characters of the rostellar hooks of Echinococcus granulosus were used to determine the origin of infection in definitive hosts in rural areas of southeastern Australia where wild and domestic cycles of transmission may interact. The morphological characters studied vary depending on the species of intermediate host (macropod marsupials, sheep) in which protoscoleces develop, and these characters are retained in adult worms. It was therefore possible to determine whether definitive hosts (dingoes and foxes) acquired infection by consuming protoscoleces of E. granulosus from macropods or from sheep. The results correlated well with the known distribution of intermediate hosts and illustrate the practical value of such morphological markers in epidemiological studies. PMID- 8437059 TI - Transplacental transmission of Wuchereria bancrofti in Haitian women. AB - To document the occurrence of transplacental transmission of microfilariae and to determine how frequently it occurred, umbilical cord blood samples and placental tissues were collected from 22 microfilaria-positive women in an area with endemic Wuchereria bancrofti. Microfilaria (mf) counts in the women ranged from 1 to 3,820 mf/ml. Microfilariae were detected in 2 placenta samples and a single cord blood sample. The positive cord blood sample and 1 of the positive placenta samples came from the same woman; no microfilariae were found in a finger prick sample taken from the infant 3 wk after delivery. Our results suggest that microfilariae cross the placenta in less than 10% of pregnancies of microfilaria positive mothers. Furthermore, the microfilaria count of the mother does not seem to influence directly whether microfilariae are present in the placental blood pool. Although actual transfer of microfilariae to the fetus may occur infrequently, exposure to parasite antigens occurs with much greater frequency. The effect of in utero exposure to either microfilariae or parasite antigens may render newborns tolerant and explain why children born to infected mothers are almost 3 times more likely to become infected than are children born to uninfected women. PMID- 8437060 TI - Effect of ultraviolet disinfection of drinking water on the viability of Cryptosporidium parvum oocysts. AB - Demineralized water was enriched with a known number of Cryptosporidium parvum oocysts obtained from fresh calf feces, which were purified and exposed to ultraviolet (UV) light (15,000 mW/sec) for different lengths of time. Coccidium free litters of CD-1 neonatal mice then were inoculated intragastrically with the treated water. Seven days postinoculation mice were killed and C. parvum infection prevalence and intensity determined. In mice inoculated with C. parvum enriched water that had been exposed to UV light for at least 150 min, no infection occurred. PMID- 8437061 TI - Safety and results of challenge of weaned pigs given a temperature-sensitive mutant of Toxoplasma gondii. AB - Two experiments were conducted to examine the responses of weaned pigs to inoculation with tachyzoites of the temperature-sensitive mutant (TS-4) of Toxoplasma gondii. Experiment 1 was done to examine the safety of the TS-4 mutant in weaned pigs given a single inoculation. No clinical sign was observed in 2 pigs inoculated subcutaneously (s.c.) (group 1) or 4 pigs inoculated intravenously (group 2) with 5 x 10(5) tachyzoites. No lesion was observed in the tissues of pigs in group 1; 3 of 4 pigs in group 2 had focal areas of gliosis and lymphocytic perivascular infiltrates in their brains. One pig also had focal areas of lymphocytic infiltrates in hepatic portal triads. No stage of T. gondii was observed in the tissues of these pigs. The TS-4 mutant was not isolated in mouse bioassay from the tissues of the 6 pigs in experiment 1. Experiment 2 was done to determine if 2 inoculations s.c. with TS-4 tachyzoites would protect pigs against inoculation orally with T. gondii oocysts. Pigs were inoculated s.c. with 5 x 10(5) TS-4 tachyzoites (4 pigs, group 3) or Hanks' balanced salt solution (4 pigs, group 4) on days 0 and 14 postinoculation (PI) and orally challenged with 1 x 10(5) oocysts of the GT-1 isolate of T. gondii 30 days PI. Clinical response to oocyst inoculation was more severe in pigs in group 4. Rectal temperatures of pigs in group 3 were significantly (P < 0.05) lower than pigs in group 4 on days 3, 4, and 9 following inoculation with oocysts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437062 TI - Isolation and in vitro cultivation of Babesia parasites from free-ranging desert bighorn sheep (Ovis canadensis nelsoni) and mule deer (Odocoileus hemionus) in California. AB - Protozoal parasites of the genus Babesia were isolated for the first time from free-ranging desert bighorn sheep (Ovis canadensis nelsoni) and mule deer (Odocoileus hemionus) populations in California by in vitro culture of host blood. These naturally infected animals did not have microscopically detectable parasitemia at the time blood was collected for parasite cultivation. Three isolates of small Babesia parasites were cultured from different sample groups of bighorn sheep, and 2 isolates of large Babesia parasites were cultured from a group of bighorn sheep and a group of mule deer, respectively. The size and structure of the various forms of piroplasms from each isolate remained consistent throughout the period of cultivation. Statistical comparison of the sizes of the piroplasms among the isolates indicated that there were at least 2 distinct morphotypes. Four of the 5 isolates were maintained with continuous growth in cultures containing erythrocytes from uninfected donor bighorn sheep, mule deer, and domestic sheep. Cryopreservation or storage of cultures at 4 C for 7 days did not affect viability of the isolates. These results demonstrate the potential for use of in vitro cultivation methods for the isolation of Babesia parasites from free-ranging artiodactylids. PMID- 8437063 TI - Role of cysteine proteinases of Entamoeba histolytica on the cytopathogenicity of axenic trophozoites on rat and hamster hepatocytes in vitro. AB - The role of amebic cysteine proteinase(s) on the in vitro cytotoxic and cytolytic effects of axenic trophozoites of a virulent strain (HM-1) of Entamoeba histolytica has been studied using freshly isolated rat and hamster hepatocytes as target cells. The cytotoxic effect was defined as cell killing without loss of cell structure and the cytolytic effect as cell disintegration. Incubation experiments of axenic trophozoites with rat or hamster liver cells in the presence and absence of bovine serum, of several proteinase inhibitors, and of galactose, galactosamine, and cysteine, at various ameba:liver cell ratios, different temperatures, and for several time periods, suggest that amebic cysteine proteinase is not involved in the cytotoxic effect but is essential for the cytolytic effect. This suggestion is supported by additional observations made with Transwell chambers, which effectively prevent contact between amebas and target cells, and by experiments with a fraction of an extract of lysed amebas that contained most of their cysteine proteinase activity. PMID- 8437064 TI - A clinical-pathological study of nonsurvivors of newborn ECMO. AB - Extracorporeal membrane oxygenation (ECMO) is an important means of supporting newborns with respiratory failure. While short- and long-term follow-up of ECMO survivors has been thoroughly addressed, there is no systematic study of nonsurvivors. Nineteen nonsurvivors of newborn ECMO with autopsy results are divided into two groups: group 1: 12 patients who had intracranial lesions as the primary cause of death (hemorrhage 8, encephalomalacia 2, infarct 2); and group 2: 7 patients with nonintracranial primary causes of death. Patients in group 1 were significantly more acidotic, hypotensive, and smaller in age and birth weight pre-ECMO. Among group 2 patients, two with diaphragmatic hernia died of primary pulmonary disease (diffuse alveolar damage, pulmonary hypoplasia and necrosis, bronchopneumonia). One of 2 patients with persistent fetal circulation (PFC) was treated with massive doses of tolazoline and suffered fatal gastrointestinal hemorrhage and ischemic necrosis of heart, spleen, testes, and adrenals. The other PFC patient had severe pulmonary interstitial fibrosis. Two patients with meconium aspiration and a patient with streptococcal sepsis had diffuse pulmonary damage and multiple organ failure (renal medullary necrosis, and infarcts of adrenal, spleen, liver). In this series, intracranial pathology was the most common cause of death in ECMO patients, related to gestational age, acidosis, hypoxia, and size, but probably unrelated to carotid ligation. PMID- 8437065 TI - Vitamin K coagulation status in surgical newborns and the risk of bleeding. AB - The vitamin K coagulation status in surgical newborns, who may be at increased risk of developing hypocoagulability and hemorrhage, has not previously been studied. Therefore, we measured the combined activity of the plasma vitamin K dependent coagulation factors (Thrombotest), total prothrombin, PIVKA II, plasma vitamin K1, fibrinogen, D-Dimer, and platelets in 49 newborns admitted to a neonatal surgical intensive care unit. All infants had significant pathology, and treatment involved surgery in all but two. Twenty-three infants (47%) underwent surgery on two or more occasions. Intravenous or oral antibiotics were used in all patients and many received more than one course. All infants had vitamin K1 prophylaxis at birth. At day 0 (date of birth), the mean Thrombotest and total prothrombin levels were 51% (range, 20% to 100%) and 40% (range, 24% to 59%), respectively. Coagulation activity decreased on day 1 (P > .1) and was followed by a graduate increase in clotting activity, reaching normal adult levels (> 60%) at day 5 for Thrombotest and day 24 for total prothrombin. Only three infants had a Thrombotest less than 20%. PIVKA II was detected in 20 cases (41%). However, levels were within normal limits (< 0.9%) in 17 of these, and between 1.0 and 4.8% in the remaining three infants. There was no relationship between elevated PIVKA levels and coagulation activity in these patients. Plasma vitamin K1 was very high, particularly in the first days of life.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437066 TI - Effect of exchange transfusion with a red blood cell substitute on neonatal hemodynamics and organ blood flows. AB - The present study was designed to evaluate the effect of a perfluorocarbon erythrocyte substitute on hemodynamics in the newborn lamb. Isovolumic double volume exchange transfusions were performed with perfluorocarbon emulsion (FC-43) on lambs who were ventilated to maintain normal acid base status. Hematocrit, fluorocrit, viscosity, arterial gas tensions, mean arterial pressure, and heart rate were determined before (control) and after (exchange) exchange transfusion. A radiolabeled microsphere technique was used and cardiac output, organ blood flow, organ vascular resistance, and oxygen delivery were calculated. As the hematocrit and viscosity decreased and the fluorocrit increased, there was a significant increase in PaO2 as well as a significant decrease in A-a gradient and oxygen content. There was no significant change in the acid-base status or the hemodynamic profile (heart rate, stroke volume, cardiac output, and mean arterial pressure). Blood flow to the heart and brain showed a significant increase, whereas flow to the cortex of the kidney showed a significant decrease. There was no significant change in flow to the gastrointestinal tract. Organ vascular resistance in the brain significantly decreased, increased in the kidney, and showed no significant change in the heart and gastrointestinal tract. Oxygen delivery significantly decreased in all organs except the heart. These data suggest that perfluorocarbon emulsions can acutely maintain hemodynamic stability in the newborn lamb and that the intrinsic properties of perfluorocarbons allow for the preservation of adequate oxygenation and acid-base status. PMID- 8437067 TI - Staged repair improves outcome of high-risk premature infants with esophageal atresia and tracheoesophageal fistula. AB - Twenty-five high-risk premature infants weighing less than 2,000 g at birth (Waterson class C), were treated for esophageal atresia (EA) and tracheoesophageal fistula (TEF). If four patients with associated Trisomy 18 are excluded for whom definitive surgery was denied, 17 of 21 patients (81%) survived. Of significance is that 14 patients with EA and TEF underwent initial gastrostomy tube placement followed by either primary anastomosis or staged repair, depending on clinical status. Four of these infants with distal TEF who were considered low risk underwent a primary anastomosis with 100% survival. However, 3 of these 4 patients developed significant postoperative complications and 2 required subsequent Nissen fundoplication (50%). Ten reached at least 2,000 g in weight with 70% survival. In this group 3 neonates died before the definitive repair could be performed. Of the 7 who survived, only 2 incurred postoperative complications and only 1 patient required Nissen fundoplication (14%). Five other patients were found to have EA without TEF and underwent staged repair with 100% survival. Finally, one additional patient with H-type TEF underwent transcervical ligation and another with a congenital esophageal stenosis died of intracerebral hemorrhage prior to the institution of surgical therapy. Although the number in this series are small, these findings suggest that premature infants with EA and TEF incur a lesser morbidity when treated by a staged repair versus a primary anastomosis. PMID- 8437068 TI - Caudal bupivacaine for postoperative analgesia in pediatric lower limb surgery. AB - One hundred children aged 1 to 15 years were randomly allocated to two equal groups. All underwent cold orthopedic surgery to the lower limb, of more than 1 hour's duration with a standard anesthetic technique. One group received caudal bupivacaine 0.25%, 0.7 mL/kg, and one group acted as controls. There were no cases of fecal incontinence in the theater complex but urinary incontinence in the immediate recovery phase increased from 14% in the control group to 34% in the caudal group (P < .05). The caudal block had a duration of effect lasting 5 to 6 hours, and provided better recovery room analgesia (P < .01). The advantages for the child are discussed. PMID- 8437069 TI - Use of intraosseous infusion in the pediatric trauma patient. AB - Intraosseous infusions (IO) are frequently used for gaining rapid vascular access in critically ill children. Few studies exist evaluating the efficacy of this procedure in the injured child. The objective of this study was to describe one pediatric institution's experience with the procedure of IO in young trauma victims. This study evaluated indications, insertion sites, complications, infused pharmacological agents, age, injury severity, and outcome. Fifteen patients received IO placement for cardiopulmonary arrest, seven for hypovolemic shock, and five for neurological compromise. Patient ages ranged from 3 months to 10 years (mean, 2.9 years). Twenty-nine IO lines were attempted in the tibia and three in the femur. Four of 32 attempts were unsuccessful. Of 32 attempts at IO placement (5 patients received multiple attempts), 15 were started in the prehospital setting and 17 in the emergency department. Multiple resuscitation medications as well as large colloid, crystalloid, and blood boluses were successfully infused. Seven of the 27 patients survived without observed IO related complications. This study supports the use of IO infusion by prehospital as well as hospital personnel in the initial resuscitation of critically injured children. IO has a been established as a rapid, safe, and simple method of obtaining short term vascular access in both critically ill and injured children. This route deserves primary consideration as an alternate route for fluid resuscitation in pediatric trauma patients regardless of age. IO should be placed without delay when venous access is not rapidly obtainable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437070 TI - Simple technique for determination of the correct length of percutaneous tunnelled catheters in neonates and children. AB - A simple technique for determining the correct catheter length in percutaneous tunnelled catheters in infants and young children has been devised that virtually guarantees accurate catheter tip placement. Sixty-six patients, aged newborn to 5 years (mean, 1.6 years) have successfully undergone this technique. It is safe, simple, precise, quick, and cost effective. It requires only a hemostat, a suture, and the supplies provided in the prepackaged catheter kit. This technique should be used whenever a percutaneous technique for accessing the vein is used and fluoroscopy is available. PMID- 8437071 TI - A posterior tunnel for the jugular venous catheter in newborns. AB - A modified technique of tunnelling for jugular venous catheters in the newborn is described. The technique eliminates cannula-kinking and offers a more convenient position for the catheter. PMID- 8437072 TI - The use of cultured epithelial autografts in the wound care of severely burned patients. AB - Commercially prepared cultured epithelial autografts permit closure of deep burn wounds when insufficient uninjured skin is available for split-thickness grafting. This technique was used in seven patients with a mean total body surface area (TBSA) burn of 66% and full-thickness burn of 52%. All patients survived with a mean initial take of 69% and final take of 80% for the cultured epithelial autografts. Patients with a TBSA burn greater than 80% required at least a second application of the grafts. We feel our approach to wound preparation and postoperative wound care has contributed to our success with this technique. PMID- 8437073 TI - Anterior cricoid suspension and tracheal stomal closure for children with cricoid collapse and peristomal tracheomalacia following tracheostomy. AB - Nearly 10% of infants with long-standing tracheostomies (> 1 year) have severe peristomal tracheomalacia and/or significant cricoid cartilage collapse. Tracheal decannulation in these small children may be complicated by upper airway obstruction, recurring respiratory tract infections, and an unsightly cervical scar. We have developed a simple one-stage method of surgically alleviating severe cricoid collapse and peristomal tracheomalacia that permits immediate extubation. After excising and transversely closing the tracheocutaneous fistula, an anterior cricoid/tracheal suspension is accomplished by suturing the adherent fibromuscular tissue overlying the cricoid and peristomal trachea to the musculofascial insertions of the cervical strap muscles adjacent to the sternum. Once tied, these sutures significantly elevate the anterior cricoid and peristomal trachea by pulling the cervical airway ventrally and inferiorly. The strap muscles cover the tracheal suture line and the skin and soft tissue are closed in a transverse fashion. This procedure has been performed in 9 children (ages 1 to 4 years). All were extubated within 24 to 72 hours. No perioperative or long-term complications were observed with follow-up averaging 20 months (range, 6 months to 4 years). Postoperative endoscopy demonstrated substantial improvement in the airway lumens of all children. The final cosmetic appearance has been excellent. This operative method of dealing with cricoid collapse and peristomal tracheomalacia is simple, safe, and effective. PMID- 8437074 TI - Posterior mediastinal masses. AB - Solid mediastinal masses in infancy and childhood occur most frequently in the posterior mediastinum. From 1972 to 1989, 63 patients presented with a posterior mediastinal mass. The median age at diagnosis was 6 years (range, 1 day to 26 years). Thirty patients were female. Forty-five percent of the patients presented with respiratory symptoms or chest pain; 13% had neurologic symptoms, one half of which were related to spinal cord compression; and 5% had a palpable mass. In 32% of patients the mass was an incidental finding. The tumors were of neurogenic origin in 89% of patients, of which neuroblastoma was the most common. Of all patients with posterior mediastinal masses, 60% had malignant tumors. Median follow-up for 62 of 63 evaluable patients was 45 months (range, 1 to 289 months). One patient was lost to follow-up. Of the 62 patients followed, 84% are alive and free of disease. All but 4 of the 32 patients with neuroblastoma are alive and free of disease with a median follow-up of 73 months (range, 7 to 289 months). Patients with neuroblastoma who were diagnosed in the first year of life had a significantly better survival pattern than those presenting after the first year. There were seven deaths in the series: four from neuroblastoma, two from primitive neuroectodermal tumor, and one from malignant schwannoma. Preoperative diagnostic evaluation of a posterior mediastinal mass should include posteroanterior and lateral chest roentgenograms, and either CT or MRI of the chest and abdomen to assess the extent of the mass.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437075 TI - Foramen of Morgagni hernia in identical twins: is this an inheritable defect? AB - Twins with Down's syndrome, foramen of Morgagni hernias, and similar cardiac anomalies are described. While diaphragmatic hernias are not uncommon, the occurrence of this congenital defect in twins with very similar congenital anomalies raises the possibility that diaphragmatic hernias may result from an inheritable defect. PMID- 8437076 TI - Decision analysis in children with blunt splenic trauma: the effects of observation, splenorrhaphy, or splenectomy on quality-adjusted life expectancy. AB - The management of blunt splenic trauma in children has remained controversial, with different physicians advocating observation, splenorrhaphy, and splenectomy. Proponents for each position have debated the relative importance of rebleeding (delayed splenic rupture), posttransfusion hepatitis with its sequelae, and overwhelming postsplenectomy sepsis. In an attempt to guide the clinician, a decision analysis was performed. Variables evaluated included the incidence of transfusion, postsplenectomy sepsis, posttransfusion hepatitis, chronic active hepatitis, cirrhosis, and rebleeding. The quality-adjusted life expectancies (QALEs) when the average incidence of the variables were used in the decision analysis were 62.69 years for observation, 62.32 years for splenorrhaphy, and 61.14 years for splenectomy. Sensitivity analysis showed that there was very little difference between observation and splenorrhaphy when the transfusion rate and hepatitis rate were varied. But these treatment options produced longer QALEs than splenectomy. Therefore, in appropriately selected patients, observation is a safe and effective therapeutic option. If an operation is necessary, every effort should be made to preserve the spleen. Splenectomy may still be required in those cases of complete devascularization, persistent hemorrhage, or other associated significant injuries. PMID- 8437077 TI - Experimental enteritis produced by high environmental temperature. AB - The authors exposed groups of Wistar rats of different average body weight to elevated environmental temperature. Necrotizing enteritis-like changes developed in the majority (up to 85%) of the animals. The best results were found in the group treated for 20 minutes at 45 degrees C, 20 minutes at rest, and 20 minutes at 56 degrees C. Subnuclear vacuolization of the enterocytes on the top of the villi intestinalis seems to be the initial event followed by subepithelial cleft formation, lifting and shedding of the epithelial cells, infiltration of the stroma by active phagocytes, and autolysis. Changes of the mesenteric blood flow can play a crucial role in the development of these lesions. PMID- 8437078 TI - Biliary tract complications in patients with hypoganglionosis and chronic idiopathic intestinal pseudoobstruction syndrome. AB - The biliary tract system was studied in two patients with hypoganglionosis and chronic idiopathic intestinal pseudoobstruction syndrome (CIIPS) to evaluate manifestations of these diseases, especially as for underlying motility disorder. In a 3-year-old boy with hypoganglionosis, cholelithiasis was diagnosed and the gallbladder specimen showed a markedly hypoplastic neural plexus on histopathology as was found in his total alimentary tract. In a 2-year-old girl with CIIPS, echo-guided gallbladder wall motility testing demonstrated an impaired response to a ceruletide diethylamine stimulation. These clinical experiences in two patients suggest that these pathological entities may be frequently associated with biliary tract complications not only due to a consequence of total parenteral nutrition, but also due to a possible intrinsic involvement of biliary tract dysmotility. PMID- 8437079 TI - The use of a long split rectal tube to aid in pull-through procedures for imperforate anus. AB - Problems with loss of correct orientation of the pull-through rectal pouch during posterior sagittal anorectoplasty (PSARP) for high imperforate anus can occur during laparotomy after perineal closure is complete. A simple modification of the de Vries-Pena technique is described that facilitates preservation of orientation and precise anatomical neomuscle construction. A slotted rubber tube preserves correct anatomical orientation of the neorectal pouch and allows accurate construction of the muscle complex around the tube. PMID- 8437080 TI - Rectal manometry, computed tomography, and functional results of anal atresia surgery. AB - Children with anal atresia often have compromised function. This is especially common with the anatomic "high lesion." Twenty-five patients have been studied using clinical evaluation, computed tomography (CT), and manometry to make an objective evaluation. The patients were an average of 9.6 years old; the male-to female ratio was 3:2. Thirty-three percent had acceptable bowel function as defined by a continence score of 1 or 2. Only two (11%) had an abnormal sacrum. The mean rectal pressure was 20 cm H2O and 5 patients (23%) had a normal rectal relaxation reflex. Thirty percent had CT scans that demonstrated an intact external sphincter and puborectalis. In comparing the objective criteria and clinical results no technique could predict continence. CT demonstrated no significant group (P = .046 to .659) and manometry demonstrated no significant group (P = .082 to .752). We found no objective criteria that could evaluate the patient's clinical result or dictate therapy. PMID- 8437081 TI - Megasigmoid: a source of pseudoincontinence in children with repaired anorectal malformations. AB - Three children with a history of anorectal malformation repairs were referred to the authors for evaluation and management of fecal incontinence. Their ages ranged from 5 to 7 years. On examination, all the children had fecal impaction and localized dilatation of the rectosigmoid colon. Medical treatment was tried but failed to control the symptoms, and the patients frequently had to be hospitalized for disimpaction. To correct this problem, the authors resected the dilated sigmoid colon, anastomosing the nondilated descending colon to the rectal ampulla, which was preserved to serve as a reservoir. Postoperatively, constipation was cured in all patients. In addition the patients became fecally continent postoperatively, which was an unexpected bonus. The authors believe that localized dilatation of the rectosigmoid should always be considered whenever a child is having intractable constipation after repair of an anorectal malformation and that sigmoid resection may be considered as a therapeutic alternative. Segmental dilatation of the sigmoid colon may be a source of fecal pseudoincontinence and, therefore, should be ruled out when the surgeon is evaluating patients with fecal incontinence. PMID- 8437082 TI - The treatment of complicated appendicitis in children using peritoneal drainage: results from a public hospital. AB - During the 2-year period from January 1, 1987 to December 31, 1988, 656 emergency appendectomies were performed on the Pediatric Surgery Service at the Los Angeles County-USC Medical Center. Of these, 398 patients were 12 years of age or less, and 227 appendices (57%) were perforated or gangrenous. The records of 167 of those patients with perforated or gangrenous appendices, treated by a standardized protocol are summarized. The protocol included perioperative antibiotics of gentamicin and clindamycin, appendectomy through a muscle splitting incision, irrigation of the peritoneal cavity with saline, and peritoneal drainage through the lateral aspect of the wound with skin closure. There was no mortality, and the major complication rate was 8%, with 3% developing intraabdominal abscesses and 5% with bowel obstructions. The minor complication rate was 11%, and included prolonged ileus and prolonged fever, with no wound infections. The average hospital stay was 8.7 days. Our experience suggests that the adopted protocol is reliable for preventing wound infections without increasing the rate of intraabdominal abscesses in an innercity population with particularly advanced stages of appendicitis. PMID- 8437083 TI - Observations of a pediatric surgeon in the Persian Gulf War. AB - In Third-World countries, infectious disease is the principal cause of childhood death and disability. During the Persian Gulf War trauma became the leading cause of death in children, prompting this review of experience with the delivery of pediatric trauma care to noncombatant children at a military hospital. Eight hundred seventy-seven patients were admitted to the 410th Evacuation Hospital from January to April 1991. Fifty of the patients (6%) were children, and 40 of the 50 were admitted for trauma. The mean age of the children was 9 years. Sixty five percent of pediatric patients sustained penetrating injuries; mechanisms of injury included shrapnel wounds, gunshot wounds, burns, motor vehicle accidents, crush injuries, and falls. The overall mortality rate for children admitted to the hospital was 12%, but no injured child died as a result of trauma. Complications of dehydration or malnutrition in infants accounted for all the deaths. PMID- 8437084 TI - Fatal bicycle accidents in children: a plea for prevention. AB - We reviewed the coroner's records of all fatal bicycle accidents occurring in children (aged 0 to 15 years) in Ontario (pediatric population, 2,007,230) between January 1, 1985 and December 31, 1989. The injuries sustained were documented and scored with anatomical injury scores (Abbreviated Injury Score 1985 and Injury Severity Score) and categorized as unsurvivable or survivable. The causes and circumstances were documented from police accident reports. Eighty one deaths resulted from bicycle accidents, an annual mortality rate of 1.44 deaths per 100,000 children per year. In 74 (91%) of these cases the injuries were deemed unsurvivable, 89% of which were head injuries. Seventy-eight (96%) of the deaths resulted from collisions with motor vehicles. No victim was wearing a helmet at the time of injury. In 70% of the deaths, the cyclist was considered to have caused the collision, either because of a violation of a road traffic law or poor road sense. These findings suggest that more emphasis should be placed on primary and secondary injury prevention by such methods as bicycle safety education for children and the promotion of bike helmet use. In addition, in view of the high incidence of unsurvivable head injury, the introduction of legislation requiring the use of protective helmets should be considered. PMID- 8437085 TI - Melanoma in childhood and adolescence: clinical and pathological features of 48 cases. AB - Forty-eight cases of melanoma occurring in patients under 20 years of age were reviewed from a 23-year period at a single center. Fourteen of the patients were preadolescent children and 44 were Caucasian. Histological review of 44 available primary tumors showed only superficial spreading and nodular types. Thickness ranged from 0.23 mm to 8.50 mm, with a median of 1.03 mm. Ulceration was present in 7%, necrosis in 35%, evidence of regression in 16%, and antecedent nevus in 49% of the cases. The overall 5-year survival is 77%, with a median follow-up of 48 months. There is no detectable survival difference between preadolescent children and adolescents. Several treatment failures occurred after improper biopsy and/or inaccurate original diagnosis of Spitz's nevus. Of 38 stage I and II patients given definitive surgical treatment by the authors, the 5-year survival is 90%. Although histological confusion with Spitz's nevi occasionally occurs, melanoma in this age group can be treated with good results. PMID- 8437086 TI - Cecoureterocele: experience of three cases with special reference to the relevance of endoscopic incision. AB - We report three cases of cecoureterocele to emphasize the salient features of this rare clinical entity. The differentiation of it from the usual ectopic ureterocele requires careful examination of the urethra by voiding cystourethrography and cystourethroscopy. We describe the management of these three cases with special reference to the endoscopic incision of the obstructing tissue. PMID- 8437087 TI - Renal hydatid disease: diagnosis and treatment. AB - Four children with renal echinococcal cyst and associated liver involvement were treated in our clinic in the last 10 years. The diagnoses were suspected by ultrasonography and computed tomography and confirmed by the operative investigation that followed. One nephrectomy, one heminephrectomy and two cystectomies were performed. All children had uneventful recovery and they have not presented any recurrence so far. The value of the diagnostic modalities and the principles of the operative management are discussed. PMID- 8437088 TI - Renal transplantation for infantile cystinosis: long-term follow-up. AB - Renal transplantation for infantile cystinosis corrects renal failure and prolongs survival. However, after transplantation, the disease may develop in the allograft and continue to progress in nonrenal organs. We studied seven children (6 boys, 1 girl) with infantile cystinosis who received 11 renal transplants (3 cadaver, 8 living-related) between May 1969 and December 1986. The age at transplant ranged from 6 to 12 years (mean, 9.1 years). Four children received second renal transplants at a mean age of 17 years (range, 16 to 22 years). The mean period of follow-up was 138 +/- 47 months. Three children received cysteamine therapy prior to transplantation. Nonrenal complications of infantile cystinosis present before transplantation were photophobia (n = 3), corneal crystals (n = 5), hypothyroidism (n = 1), rickets (n = 6), and short stature (n = 7). Graft and patient survival did not differ from controls matched for the time of transplantation. Two patients died (1 pneumococcal sepsis, 1 respiratory failure due to pulmonary fibrosis) with functioning grafts 5 and 14 years posttransplant. Complications that developed posttransplant included photophobia (n = 1), corneal crystals (n = 2), hypothyroidism (n = 4), polyneuropathy (n = 1), pulmonary fibrosis (n = 1), abnormal electroencephalogram without clinical seizures (n = 1), bladder stones (n = 1), and diabetes mellitus (n = 2). One patient received a corneal transplant. All seven children failed to show improvement in growth following transplantation. Cystine crystals are present in graft-infiltrating cells, but do not seem to affect kidney allograft function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437089 TI - Suprapubic dermoid sinus. AB - Two newborns with suprapubic sinuses ending in relationship to the urachus at the umbilicus are reported. Other recent reports indicate that these sinuses are not so uncommon and are due to abnormalities of urachal development in conjunction with a suprapubic dermoid sinus. PMID- 8437090 TI - Predictors of postoperative respiratory complications in premature infants after inguinal herniorrhaphy. AB - There is a significant incidence of inguinal hernia in premature infants and the optimal timing of repair is controversial. A high rate of postoperative respiratory complications has been reported in this group. In this study, the records of 47 premature infants (mean gestational age, 30.3 weeks) who underwent herniorrhaphy while still in the neonatal intensive care unit were reviewed in an effort to define those conditions that are independent risk factors for complications. Forty-three percent of infants had complications, including postoperative assisted ventilation (34%), episodes of apnea and/or bradycardia (23%), emesis and cyanosis with first feeding (6%), and requirement for postoperative reintubation (4%). Although low gestational age and postconceptual age at operation, low birth weight for gestational age, and preoperative ventilatory assistance were significantly associated with postoperative complications, only a history of respiratory distress syndrome/bronchopulmonary dysplasia (odds ratio 2.3), a history of patent ductus arteriosus (odds ratio 2.5), and low absolute weight at operation (odds ratio 3.5 for 1,000-g decrease) were independent risk factors for postoperative complication. Despite previous reports citing postconceptual age as the factor having the greatest impact on postoperative complications, these results indicate that a history of respiratory dysfunction and size at operation may be more important predictors of postoperative respiratory dysfunction in preterm infants. PMID- 8437091 TI - Abdominoscrotal hydrocele in childhood. PMID- 8437092 TI - A case of benign intrascrotal lipoblastoma clinically mimicking testicular torsion and review of the literature. PMID- 8437093 TI - Ingested foreign body presenting as an irreducible inguinal hernia in a baby. AB - A case of a 7-month-old boy, presenting as an emergency with an inguinal swelling, is reported. An ingested safety pin caused a colonic perforation in the congenital hernial sac. This was successfully treated by herniotomy and local colonic resection. PMID- 8437094 TI - Inguinal-scrotal suppuration following treatment of perforated appendicitis. AB - Suppuration of a congenital hernia or communicating hydrocele following generalized peritonitis is rare. The lack of reported cases in the recent literature may indicate a decreasing incidence of this unusual complication. We report a case of suppuration of a communicating hydrocele with testicular loss 2 days after treatment of perforated appendicitis in a 10-year-old boy. PMID- 8437095 TI - True duplication of the vas deferens. AB - We report true duplication of the vas deferens found at routine inguinal hernia repair. This rarity is described in the context of the embryologic model for other vas abnormalities. PMID- 8437096 TI - Leiomyosarcoma of the saphenous vein in a child with 12-year follow-up. AB - Leiomyosarcomas of the vasculature are exceedingly rare tumors in childhood. The case of a 2-year-old girl who underwent three local excisions with two courses of adjuvant chemotherapy over 3 years for a leiomyosarcoma of a saphenous vein tributary is described. Follow-up over the following 9 years has shown no evidence of further recurrence or metastases suggesting that cure has been achieved. Treatment options are discussed and pertinent literature is reviewed. PMID- 8437097 TI - Development of a new operation for the repair of rectovestibular fistulas in females with anorectal malformations. PMID- 8437098 TI - Disappointing long-term results of antireflux surgery in profoundly disabled children. PMID- 8437099 TI - The prenatal diagnosis of imperforate anus with rectourinary fistula. PMID- 8437100 TI - The insertion of a soft Silastic nasogastric tube at an operation for an esophageal atresia. PMID- 8437101 TI - Expression and characterization of the rat D3 dopamine receptor: pharmacologic properties and development of antibodies. AB - A baculovirus expression system provided an enriched source of biologically and immunologically active D3 dopamine receptors. Receptors expressed in Spodoptera frugiperda insect (Sf9) cells at a density of 5 to 15 pmol/mg of protein displayed high affinity for the antagonists, eticlopride, fluphenazine and spiroperidol, and the agonist, N-propylnorapomorphine. The binding of agonists was not sensitive to GTP. Antisera raised against synthetic peptides in the third intracellular loop of the D3 dopamine receptor immunoprecipitated binding sites for (S)-3-[125I]-iodo-2-hydroxy-5,6-dimethoxy-N-[(1-ethyl-2-pyrrolidinyl)- methyl]-benzamide from solubilized extracts of infected Sf9 cells and detergent extracts of rat caudate. These antisera specifically recognized a single band on immunoblots of Sf9 cells infected with recombinant D3 baculovirus. Both the immunoprecipitation and immunoblot reactions were blocked by preincubation of the antisera with the immunization peptide. These results suggest that the D3 receptor protein is expressed in rat brain. PMID- 8437102 TI - Interleukin-1 beta differentially represses drug-metabolizing enzymes in arthritic female rats. AB - Experimental arthritis and inflammation have been reported to reduce liver cytochrome P-450-dependent mono-oxygenase activities with subsequent impairment of drug metabolism. Interleukin-1 beta (IL-1) is among the proven mediators of both inflammation and P-450 decrease, although some paradoxical effects were sometimes reported in experimental models of arthritis. The aim of the present study was to evaluate the main liver drug-metabolizing isoenzymes during established collagen-induced arthritis in rats, and to investigate whether a systemic IL-1 treatment was able to mimic or sometimes to reverse the influence of the inflammatory process on these enzymes. Arthritis was induced on day 0 by type II collagen and a low dose (0.2 mg) of N-acetylmuramyl-L-alanyl-D isoglutamine, and human recombinant IL-1 was administered s.c. at the daily dose of 0.02, 0.2 or 2.0 micrograms per arthritic rat, from day 21 to 25 and on day 28. Ethoxyresorufin-O-deethylation was depressed 6-fold in arthritic rat liver microsomes and the highest dosage of IL-1 potentiated this depression. Pentoxyresorufin-O-deethylation decreased by 50% in arthritic rat, a dose dependent decrease being observed after IL-1 treatment. Progesterone 6 beta hydroxylation and P-450 IIIA protein increased by 2-fold in both untreated arthritic rat liver microsomes and those treated by the lowest dose of IL-1. The two higher doses decreased this activity, vs. the dose, to reach the naive level. Lauric acid hydroxylation increased 2-fold in arthritic rat and was further potentiated by IL-1. UDP glucuronosyl transferase IA2 activity was increased 2 fold in arthritic rats, with subsequent decrease after 2.0 micrograms of IL 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437103 TI - Inhibition of the Na(+)-Ca++ exchanger enhances anoxia and glucopenia-induced [3H]aspartate release in hippocampal slices. AB - The aim of the present study was to investigate the possible role played by the Na(+)-Ca++ exchange system in the modulation of D-[3H]aspartate release induced by anoxia and glucopenia from hippocampal slices. When hippocampal slices were exposed to anoxic and glucopenic conditions (oligomycin + 2-deoxyglucose or 95% N2/5% CO2), an increase of basal D-[3H]aspartate release occurred. Two organic calcium entry blockers, verapamil and nimodipine, and the inorganic calcium entry blocker, gadolinium, did not prevent anoxia-induced D-[3H]aspartate release. In contrast, the calcium-chelator, EGTA, and lanthanum, an inorganic compound that blocks voltage-sensitive calcium channels and Na(+)-Ca++ exchanger activity, enhanced anoxia-induced D-[3H]aspartate release. In addition, the 2'-4' dimethylbenzil amiloride derivative, a rather specific inhibitor of the Na(+) Ca++ exchanger system, enhanced anoxia-induced D-[3H]aspartate release. Finally, tetrodotoxin, which selectively blocks the Na(+)-channels, attenuated anoxia elicited D-[3H]aspartate release. In conclusion, the results of the present study confirmed that, under anoxic and glucopenic conditions, D-[3H]aspartate release was not dependent on the entrance of extracellular Ca++ ions through the voltage sensitive calcium channels and demonstrated that the inhibition of the Na(+)-Ca++ antiporter enhanced excitatory amino acid release. This result seems to suggest that, when intracellular Na+ concentrations increase, because of the anoxic and glucopenic conditions, both the Na(+)-Ca++ exchanger and the Na(+)-syntransporter system of glutamate operate as Na+ ion efflux pathways. Therefore, when the antiporter is blocked, the syntransporter remains the only pathway for Na+ ion extrusion, leading to an enhancement of D-[3H]aspartate release. PMID- 8437104 TI - Differential effects of alkylating agents on the multiple muscarinic receptor subtypes linked to activation of phospholipase C by carbachol in rat brain cortical membranes. AB - Muscarinic cholinergic receptor function in rat brain cortex was characterized by performing binding assays with [3H](-)quinuclidinyl benzilate ([3H]QNB) in parallel with assays of phospholipase C (PLC) activation by carbachol using membrane preparations and exogenous [3H]-phosphatidylinositol 4,5-bisphosphate ([3H]PIP2). Competitive binding studies revealed high- and low-affinity binding sites for the receptor antagonists, pirenzepine, methoctramine and the p-fluoro analog of hexahydro-sila-difenidol (p-F-HHSiD). Carbachol-stimulated [3H] phosphatidylinositol 4,5-biphosphate breakdown was specifically inhibited by pirenzepine and p-F-HHiSD. The inhibition curves for these antagonists were best described by interactions at two sites. There was quantitative agreement between the antagonist affinity constants and the proportion of high- and low-affinity sites derived in functional and binding studies. The characteristics of the putative subtypes of muscarinic receptors and their stimulation of phospholipase C was examined after treatment with two alkylating agents, N-ethoxycarbonyl-2 ethoxy-1,2-dihydroquinoline and propylbenzilylcholine mustard. Loss of receptors was closely correlated with loss of PLC activation by carbachol, without alteration of the EC50 value (21 microM) of this agonist, clearly demonstrating a lack of receptor reserve. When both alkylating treatments were adjusted to induce a decrease of 60% in the maximal number of [3H]QNB binding sites, a similar (60%) reduction in the maximal effect of carbachol on PLC activation was found. However, the characteristics of the remaining receptors after the treatment with the two alkylating agents differ markedly as determined by competition of pirenzepine, p-F-HHSiD and methoctramine for [3H]QNB binding, and for inhibition of carbachol-stimulated phospholipase C by pirenzepine and p-F-HHSiD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437105 TI - Effects of intermittent buprenorphine administration on cocaine self administration by rhesus monkeys. AB - In previous studies, daily buprenorphine administration significantly reduced cocaine self-administration by rhesus monkeys over 15 to 120 days (Mello et al., 1990, 1992). This report describes the effects of 60 days of intermittent buprenorphine (0.40 mg/kg) treatment once every 48 hr or 72 hr on cocaine and food self-administration by six rhesus monkeys. Cocaine (0.05 or 0.10 mg/kg/injection) and food (1-g banana pellet) self-administration were maintained on a fixed ratio 4, (variable ratio 16:S) reinforcement schedule. Intermittent buprenorphine treatment reduced cocaine self-administration significantly below saline treatment levels (P < .01). On the first day of buprenorphine treatment, cocaine self-administration averaged 53 and 60% below base line (P < .01-.0001). Cocaine self-administration remained significantly below base line on day 2 (P < .02-.0001) but usually returned to base-line levels by day 3. During buprenorphine treatment once every 48 hr, cocaine self-administration gradually increased over time in four monkeys (P < .001-.0005). These data suggest that intermittent buprenorphine treatment is less effective than daily buprenorphine treatment in reducing cocaine self-administration by rhesus monkeys. Food self administration decreased by 23.6 and 12.7% from the saline base line during buprenorphine treatment every 48 and 72 hr, respectively. On the day of buprenorphine treatment, food self-administration was usually significantly lower than during the saline base line (P < .05-.0001), but usually returned to or exceeded base line levels by days 2 and 3. There were no significant changes in food self-administration over time with intermittent buprenorphine treatment every 48 hr. PMID- 8437106 TI - Nicotinic receptor function determined by stimulation of rubidium efflux from mouse brain synaptosomes. AB - The ability of nicotinic agonists to activate ion channels resulting in Na+ and K+ fluxes has been used to develop a functional assay by using mouse brain synaptosomes. Synaptosomes prepared using Percoll gradients were enriched in binding sites for [3H]nicotine and were capable of accumulating the K+ analog, 86Rb+. The efflux of 86Rb+ from the synaptosomes was subsequently monitored using continuous superfusion at 21 degrees C. Ion flux was stimulated in a concentration-dependent manner by several nicotinic agonists, including L nicotine, acetylcholine, N-methylcarbamylcholine and dimethylphenylpiperazinium. The process was stereoselective: L-nicotine was 30-fold more potent than D nicotine. Cytisine stimulated ion flux at low concentrations, but this drug was less efficacious than most other agonists tested. Anabasine was also less efficacious than the other agonists. The EC50 values for agonist-stimulated efflux correlated closely to the IC50 values for inhibition of [3H]nicotine binding, but concentrations required to inhibit binding were lower than those required to stimulate ion flux. Nicotine-induced 86Rb+ efflux was blocked by several nicotinic antagonists including mecamylamine, D-tubocurarine, hexamethonium and decamethonium. Mecamylamine was approximately 50 times as potent as hexamethonium. Neither alpha-bungarotoxin nor atropine were effective antagonists and neuronal-bungarotoxin was a relatively ineffective inhibitor. The amount of nicotine-induced efflux varied among brain regions with midbrain (thalamus and mesencephalon) having the largest response and cerebellum the smallest. The magnitude of the ion flux correlated closely with the amount of [3H] nicotine binding in each brain region. The results indicate that a nicotinic receptor-mediated ion flux can be measured in brain tissue and that the ion flux may serve as a useful functional assay for nicotinic receptors in the central nervous system. Furthermore, it is postulated that the nicotinic-agonist stimulated ion flux may be mediated by receptors measured by high affinity [3H]nicotine binding. PMID- 8437107 TI - Two delayed rectifiers in guinea pig ventricular myocytes distinguished by tail current kinetics. AB - The delayed rectifier potassium current was studied in single guinea pig ventricular myocytes using the whole cell voltage clamp technique. Previous pharmacologic data indicated that the delayed rectifier in this preparation was a composite of two channel types (Sanguinetti and Jurkiewicz, 1990a; Balser et al., 1990). In guinea pig, the delayed rectifier tail current can be fit by the sum of two exponential functions having fast (approximately 125 ms) and slow (approximately 750 ms) decay time constants. The new findings here are as follows: 1) the fast decay phase derives solely from a channel type separable by voltage pulse protocol and the benzenesulfonamide agent, E-4031. In response to pulses of increasing duration, the fast phase amplitude increased to a plateau within 0.5 sec, whereas the slow phase required 3 to 6 sec. 5 microM E-4031 completely blocked the fast phase. 2) Whereas the drug-insensitive current contained only a slow decay phase, the drug-sensitive tail current contained a slow phase in addition to a fast decay phase. Both phases increased in amplitude in parallel with the drug-sensitive time-dependent current, indicating the existence of only one drug-sensitive channel. These pharmacologic and physiologic data will help define the characteristics of drug-sensitive and -insensitive currents. Furthermore, they indicate that the fast phase of tail current decay observed in the absence of drug represents a distinct channel type. PMID- 8437108 TI - Pharmacological profile of BMS 180,291: a potent, long-acting, orally active thromboxane A2/prostaglandin endoperoxide receptor antagonist. AB - 180,291 1S-(1 alpha, 2 alpha, 3 alpha, 4 alpha)-2-[[3-[4- [(pentylamino)carbonyl] 2-oxazolyl]-7-oxabicyclo[2.2.1]hept- 2- yl]methyl]benzenepropanoic acid (BMS) is a potent and highly selective antagonist of thromboxane A2/prostaglandin endoperoxide (TP) receptors. In human platelet-rich plasma, BMS 180,291 inhibited platelet aggregation induced by arachidonate (800 microM) and U-46,619 (10 microM) with respective IC50 values of 7 +/- 1 (S.E.M.) and 21 +/- 2 nM. Inhibition of both the rate and full extent of 11,9-epoxymethano-prostaglandin H2 (U-46,619)-induced platelet aggregation were insurmountable at antagonist concentrations > 10 nM, but BMS 180,291 antagonized U-46,619-induced platelet shape change competitively with a KB of 11 +/- 2 nM. BMS 180,291 concentrations < or = 1 mM did not inhibit platelet aggregation induced by high concentrations of ADP (20 microM) or human alpha-thrombin (1 U/ml). BMS 180,291 inhibited binding of [3H]1S-[1 alpha,2 alpha(5Z),3 alpha,4 alpha]-7-[3-[[2- [(phenylamino)carbonyl]hydrazino]methyl]-7-oxabicyclo[2.2.1]-hept-2- yl]-5 heptenoic acid to human platelet membranes with a kd of 4.0 +/- 1.0 nM and slope factor of 1.06 +/- 0.13. U-46,619-induced concentrations of rat aortae were competitively antagonized by BMS 180,291 with a KB of 0.6 +/- 0.1 nM. Aortic responses to norepinephrine, serotonin and angiotensin II were not inhibited by BMS 180,291 at 1 microM. U-46,619-induced contractions of guinea pig tracheal rings were antagonized in an almost all-or-none manner, with maximal blockade at > or = 1 nM BMS 180,291, but little effect at lower concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437109 TI - Characterization of glomerular thromboxane receptors in murine lupus nephritis. AB - Renal thromboxane (Tx) production is increased in the MRL-lpr murine model of lupus nephritis. To investigate the relationship between increased Tx production and number and affinity of Tx receptors, we measured binding of the Tx receptor antagonist [3H][SQ295481S-1 alpha,2 beta(5Z),3 beta,4 alpha]-7-(3-((2-((phenyl- amino)-carbonyl)hydrozino)methyl)-7-oxabicyclo-(2.2.1)heptan -2-yl)-5-heptenoic acid in glomerular preparations from MRL-lpr mice and both MRL(-)+/+ and LG/J controls. Renal Tx binding was first characterized in normal LG/J mice. In these animals, glomerular binding was specific, saturable and reversible. Scatchard analysis revealed a single class of high-affinity binding sites. We next evaluated Tx production and binding in 12- and 16-week-old MRL-lpr mice and MRL( )+/+ controls. To assess renal Tx production, excretion of TxB2 was measured in urine. Urinary TxB2 was increased in MRL-lpr mice at 16 weeks of age. This increase in urinary TxB2 was associated with a reduction in density of glomerular Tx binding sites compared to either 12-week-old MRL-lpr mice or MRL(-)+/+ controls. Ligand binding affinity was similar in all groups. To investigate if this alteration in binding was specific for Tx, glomerular binding of [3H]angiotensin II was measured. In MRL-lpr mice, the number and affinity of glomerular angiotensin binding sites were similar at 12 and 16 weeks of age. Thus, in this murine model of lupus nephritis, enhanced renal Tx production is temporally associated with a decrease in glomerular Tx binding sites without a change in receptor affinity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437111 TI - A micropuncture study on the renal site of action of ICI 206,970, a unique eukalemic diuretic. AB - The site of action of ICI 206,970, an aminomethylphenol pyrazine derivative, with effects on Na+ and water excretion similar to hydrochlorothazide, was determined using free-flow micropuncture and in vivo microperfusion techniques. Furosemide and ICI 206,970 were perfused into the loop of Henle, at a concentration of 10( 4) M. Furosemide reduced water, Na+ and K+ reabsorption by the loop, but ICI 206,970 had little effect. Amiloride and ICI 206,970 were perfused into the distal nephron at a concentration of 10(-4) M. Both compounds reduced the reabsorption of Na+ and secretion of K+, ICI 206,970 having a somewhat greater effect than amiloride at this dose. ICI 206,970 also reduced water reabsorption by the distal tubule. ICI 206,970 was infused i.v. at a dose of 10 mg/kg/hr into anesthetized rats, and its effect on reabsorption by various nephron segments was determined. This compound tended to reduce proximal reabsorption of Na+, K+ and water, but had little effect on reabsorption of electrolytes and water by the loop of Henle, or distal tubule reabsorption of Na+ and water. Distal K+ secretion decreased after administration of ICI 206,970. Reabsorption of electrolytes and water beyond the late distal nephron was not affected by the drug. Urinary excretion of Na+ and water was elevated, but K+ excretion remained unchanged after treatment with ICI 206,970. The sites of action of ICI 206,970 appear to be the proximal and distal nephron. Urinary excretion of Na+ and water was largely dependent on the effect of ICI 206,970 on proximal reabsorption, as this compound had little effect on loop of Henle or distal tubule reabsorption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437110 TI - Cytokine reversal of morphine-induced suppression of the antibody response. AB - Female C3HeB/FeJ mice implanted with a morphine pellet exhibit a decreased primary antibody response in vitro as measured by the plaque-forming cell (PFC) assay. Suppression was detected at 24 hr following pellet implantation, was maximal at 48 hr and returned to normal by 120 hr. Splenocytes from control mice cocultured with splenocytes from morphine-treated mice (3:1 ratio) did not show a significant suppression, suggesting that morphine is not inducing the production of suppressor cells and/or factors. However, cells from morphine-treated mice cocultured with control cells (3:1) had a restored response. Further coculture experiments demonstrated that addition of adherent cells, but not nonadherent cells, restored the antibody response, suggesting that the macrophages from morphine-treated mice were deficient or defective. In vitro addition of interleukin (IL)-6, IL-1 beta or interferon-gamma (0.5-50 U/ml) attenuated the suppression of the PFC response in cells from morphine-treated mice, whereas higher doses (100 U/ml) restored completely the PFC response to control levels. Addition of IL-2, IL-4 or IL-5 to cultures from morphine-treated mice had little effect. Thus, morphine appears to cause immune suppression by reducing macrophage numbers or by interfering with the production or release of specific cytokines which are needed for a normal antibody response. Collectively, these data suggest that the macrophage is a key cellular target for the suppressive effects of morphine on the antibody response. PMID- 8437112 TI - Pulmonary antiallergic and bronchodilator effects of isozyme-selective phosphodiesterase inhibitors in guinea pigs. AB - The effectiveness of theophylline (aminophylline) in treating asthma may result in part from nonselective inhibition of multiple isozymes of cyclic nucleotide phosphodiesterase (PDE). The roles for inhibition of different PDE isozymes in the pulmonary antiallergic and bronchodilator effects of theophylline were investigated in anesthetized and ventilated guinea pigs by using the PDE-III selective inhibitor Cl-930, the PDE-IV-selective inhibitor rolipram and the PDE-V selective inhibitor zaprinast. Aminophylline, Cl-930 and rolipram inhibited aerosol ovalbumin-induced full [leukotriene (LT) + histamine] and LT-dependent bronchoconstriction, but zaprinast was inactive. At doses producing an equieffective inhibition of antigen-induced full bronchoconstriction, aminophylline and Cl-930 produced a similar inhibition of aerosol histamine induced bronchoconstriction, whereas rolipram produced much less inhibition of histamine-induced bronchoconstriction. At doses producing an equieffective inhibition of antigen-induced LT-dependent bronchoconstriction, aminophylline and Cl-930 produced a similar inhibition of i.v. LTD4-induced bronchoconstriction, whereas rolipram did not inhibit LTD4-induced bronchoconstriction. Acute airway hyperreactivity was evidenced by significant leftward shifts in dose-response curves to i.v. methacholine-induced bronchoconstriction 24 hr after aerosol ovalbumin challenge. Aminophylline and rolipram prevented airway hyperreactivity without causing residual bronchodilation 24 hr after antigen challenge. In contrast, Cl-930 failed to inhibit airway hyperreactivity, but produced substantial residual bronchodilation. The results indicate that PDE-IV inhibition produces pulmonary antiallergic effects in vivo, including the apparent inhibition of LT release, which may contribute to the antiasthmatic actions of theophylline. The results also support previous suggestions that PDE-III inhibition contributes to the bronchodilator effect of theophylline. PMID- 8437113 TI - Pharmacological analyses of endo-6-methoxy-8-methyl-8-azabicyclo[3.2.1]oct-3-yl 2,3-dihydro-2-oxo-1 H- benzimidazole-1-carboxylate hydrochloride (DAU 6285) at the 5-hydroxytryptamine4 receptor in the tunica muscularis mucosae of rat esophagus and ileum of guinea pig: role of endogenous 5-hydroxytryptamine. AB - Functional estimates of affinity for endo-6-methoxy-8-methyl-8- azabicyclo[3.2.1]oct-3-yl-2,3-dihydro-2-oxo-1H-benzimidazole-1-carboxyla te hydrochloride (DAU 6285) were made at the 5-hydroxytryptamine4 (5-HT4) receptor in isolated preparations of rat esophageal tunica muscularis mucosae (TMM) and guinea pig ileum. In the TMM, relaxation of carbachol-induced contracture by 5 HT4 receptor agonism of longitudinal muscle was recorded. Estimated pA2 values for DAU 6285 of 6.9 to 7.2 were tissue, time (1-3 hr equilibration) and agonist independent. However, DAU 6285 increased the maximal response to 5-HT and 5 methoxytryptamine in the TMM and augmented the contractile tone to carbachol. These effects were not observed in guinea pig ileum, suggesting a tissue dependent mechanism. [3a-Tropanyl]-1H-indole-3-carboxylic acid ester (tropisetron) and 2-methoxy-4-amino-5-chloro-benzoic acid 2-(diethylamino)ethyl ester (SDZ 205-557), two other 5-HT4 receptor antagonists, mimicked the effects of DAU 6285. Mechanistic experiments suggest agonism by endogenous 5-HT, within the isolated TMM, to explain the effects of 5-HT4 receptor antagonists. Pretreatment of rats with parachlorophenylalanine to deplete endogenous 5-HT, prevented the effect of DAU 6285 on the maximal response to 5-HT and carbachol induced tone. In conclusion, DAU 6285 acts as a silent, competitive antagonist at 5-HT4 receptors in rat TMM and guinea pig ileum. However, in the TMM, endogenously released 5-HT confounds interpretation. The TMM, as a quantitative assay system for 5-HT4 receptor agonists and antagonists may be improved by pretreating rats with parachlorophenylalanine. PMID- 8437114 TI - Carbonic anhydrase inhibitory activity and ocular pharmacology of organic sulfamates. AB - Organic sulfamates are a new variation to the carbonic anhydrase (CA) inhibitor structure-action relationship. Inhibitory activity is conferred by the classic sulfonamide group, but through linkage to the benzene ring by an oxygen. AHR 16329, a representative sulfamate, has an acidic (sulfonamide, pKa 8.9) and basic (imidazole, pKa 6.0) group and has desirable physicochemical properties for topical intraocular pressure lowering: good water solubility below pH 6.0, a CHCl3/buffer ratio of 0.5 at pH 7.0 and a Kl against CA-II of 7 nM. Inhibition of CO2 hydration is noncompetitive. When applied locally to the eye, AHR-16329 reaches significant levels in ocular tissues and fluids and reduces significantly intraocular pressure. Five percent concentration gives the greatest reduction, equivalent to systemic inhibitors; 2 and 5% have similar pressure x time duration. These studies expand structure-action relations in the field of CA inhibitors and the validity of developing topical CA inhibitors for treatment of glaucoma. PMID- 8437115 TI - Bis(5-amidino-2-benzimidazolyl)methane and related amidines are potent, reversible inhibitors of mast cell tryptases. AB - Tryptase is the major secretory protease of human mast cells and is proposed to be involved in neuropeptide processing and tissue inflammation. Exploration of the biology of tryptase has been hindered by the lack of potent, selective inhibitors. The current study explores the properties of aromatic diamidines as inhibitors of dog and human tryptase. The strongest inhibitors of tryptase in this series are bis(5-amidino-2-benzimidazolyl)methane (BABIM) and (5-amidino-2 benzimidazolyl)-(5-(N,N'-dimethylamidino)-2- benzimidazolyl)methane, which exhibit K(i) values of 1.8 and 1.4 nM, respectively, in blocking the hydrolysis of tosyl-L-Gly-Pro-Lys-4-nitroanilide by human tryptase. These compounds are approximately 10,000-fold more potent than benzamidine, and are the strongest reversible inhibitors of tryptase described to date. Other aromatic mono- and diamidines, including amiloride and pentamidine, are less potent. Nonetheless, they abolish tryptase activity at high inhibitor concentrations. The rank order of tryptase inhibitor potency parallels that of inhibitors tested against trypsin. BABIM, the only highly active member of this series whose potency against other targets has been examined previously, is a far stronger inhibitor of tryptase than of other trypsin-like serine proteases, including those involved with hemostasis, fibrinolysis and the complement system. Therefore, BABIM appears to have selective affinity for tryptase. In addition to inhibiting tryptase induced hydrolysis of peptide-based chromogenic substrates, BABIM blocks completely the reversal of vasoactive intestinal peptide-induced relaxation of isolated trachea by dog tryptase. Thus, BABIM and related amidines are potent inhibitors of mast cell tryptases that may be useful in exploring mast cell protease biology. PMID- 8437116 TI - Alteration in the modulatory role of respiratory epithelium after exposure of guinea pigs to respirable cotton dust. AB - Chest tightness may occur after inhalation of cotton dust. To understand the origins of this symptom of byssinosis, we exposed guinea pigs to respirable cotton dust and determined whether the resulting pulmonary obstruction was associated with alterations in the in vitro reactivity of the trachea to methacholine. The isolated, perfused trachea preparation was utilized because it allows a comparison of airway smooth muscle responses to drugs after they are applied separately to the mucosal or serosal surfaces. In epithelium-containing control tracheae, mucosally applied methacholine was less potent and elicited smaller maximum contractile responses than those obtained when it was applied to the serosal compartment. After a 6-h inhalation exposure to 30 mg/m3 respirable cotton dust, the mucosal maximum response to methacholine was substantially increased immediately (0 h) after the end of the exposure, but it was decreased 18 h postexposure. A dust level of 10 mg/m3 produced modest increases in the mucosal maximum responses at both postexposure periods, elevating them to the magnitude of the extraluminal maximum response. The potency of serosally applied methacholine was not affected by any cotton dust exposure. Mechanical epithelium removal increased mucosal reactivity to the serosal level in both control and cotton (30 mg/m3)-exposed groups, and abolished the effects of dust on mucosal reactivity to methacholine. Our findings suggest that the modulatory effect of the epithelium may be inhibitory or excitatory. The balance between the two influences may be altered by inhaled cotton dust. PMID- 8437117 TI - Nereistoxin: a naturally occurring toxin with redox effects on neuronal nicotinic acetylcholine receptors in chick retina. AB - Nereistoxin (NTX; 4-N,N-dimethylamino-1,2-dithiolane) is previously reported to block both muscle and neuronal nicotinic acetylcholine receptors, and reversibly inhibit radioligand binding to Torpedo nicotinic receptors. Here, we studied redox effects of NTX on neuronal nicotinic receptors in chick retinas by electrophysiological recordings and by [125I]neuronal bungarotoxin binding. NTX blocked retinal responses to the nicotinic agonist dimethylphenylpiperazinium (300 microM, 2 sec) with an IC50 of 3.5 microM. NTX inhibition was selective for nicotinic receptors, long lasting and not reversible upon washing. The nonselective oxidizing compound dithiobis(nitrobenzoic acid) (1 mM) transiently and repetitively reversed NTX (100 microM) inhibition (85% recovery). After application of the alkylating agent bromoacetylcholine (2 or 100 microM, with 2 microM neostigmine), dithiobis(nitrobenzoic acid) could no longer restore nicotinic function. d-Tubocurarine (300 microM) equally protected against alkylation with bromoacetylcholine (2 microM) after dithiothreitol (2 mM) or NTX treatment. The action of NTX differs from that of dithiothreitol because the agonist dimethylphenylpiperazinium (30 microM) protects against inactivation by dithiothreitol, but not by NTX. NTX reversibly inhibited [125I]neuronal bungarotoxin binding to chick retinal homogenates (IC50 = 16 microM). The present study suggests that nereistoxin or a metabolite is a potent antagonist as well as a selective reducing agent for nicotinic receptors in chick retina. As a dithiolane, this latter action by nereistoxin remains to be explained. PMID- 8437118 TI - Nucleotides modulate the low affinity binding sites for [3H]glibenclamide in the rat brain. AB - Receptors for hypoglycemic sulfonylureas, such as glibenclamide, are commonly linked to the activity of ATP-sensitive K+ channels (K-ATP). High and low affinity binding sites for glibenclamide were described previously in numerous tissues. High affinity binding sites have been thought to be responsible of the modulation of K-ATP, but new evidences suggest that low affinity ones could also regulate these channels. In order to clarify the properties of the two binding sites, with respect to their interaction with K-ATP, we characterized biochemically and pharmacologically [3H]glibenclamide binding in the rat brain cortex. Competitive inhibition plots with [3H]glibenclamide performed on membranes of adult and neonatal rat brain cortex exhibited a biphasic pattern with similar binding parameters, indicating the presence of two similar binding sites in adult as well as in neonatal animals. Membranes of adult rat cortex treated with thiol groups modifying agents, N-ethylmaleimide or 1,4 dithiothreitol, increased the inhibition constant of glibenclamide for the low affinity binding sites (K(i)L) by about 4-fold. The divalent cations Mg++ and Ca++ also increased K(i)L by 3- to 6-fold and enhanced the low affinity binding capacity (BmaxL) by 55 and 103%, respectively, both cations increasing BmaxL by 144%. Among the numerous nucleotides studied, adenine and guanidine triphosphate nucleotides were the most potent to affect the low affinity binding sites. ATP, ADP, GTP and respective nonhydrolysable nucleotides increased K(i)L by 7- to 12 fold and decreased BmaxL by 10 to 30%. The effects of nucleotides were not Mg++ dependent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437119 TI - Endothelial relaxing 5-hydroxytryptamine receptors in the rat jugular vein: similarity with the 5-hydroxytryptamine1C receptor. AB - Serotonin (5-HT) at low concentrations induces an endothelium-dependent relaxation in the rat jugular vein mediated via a 5-HT1-like receptor. The receptor mediating this relaxation was characterized in vitro using agonists and antagonists in segments precontracted with prostaglandin F2 alpha in the presence of the 5-HT2 receptor antagonist ketanserin. The following substances acted as agonists, with the order of potency: 5-HT > dl-alpha-methyl-5-hydroxytryptamine = 5-carboxamidotryptamine > quipazine > 8-hydroxy-2-(dl-n-propylamino) tetralin. dl Propranolol, mesulergine and mianserin acted as competitive, methysergide, 6 methyl-1-(1-methylethyl)-ergoline-8 beta-carboxylic acid 2-hydroxy-1-methylpropyl ester and sumatriptan as non-competitive, and ritanserin acted as both a competitive and non-competitive antagonist of the 5-HT-induced relaxation. Neither the 5-HT2 antagonists ketanserin and spiperone nor the 5-HT3 antagonist 1 alpha-H,3 alpha,5 alpha-H-tropan-3-yl,3,5-dichlorbenzoate affected the 5-HT induced relaxation. The pEC50 values of the agonists and the pA2 and pAh values of the antagonists correlated strongly with pKD values at the 5-HT1C binding site. These results are consistent with a peripheral vascular 5-HT1C receptor in the rat jugular vein. PMID- 8437120 TI - Inhaled 1,1,1-trichloroethane-produced physical dependence in mice: effects of drugs and vapors on withdrawal. AB - 1,1,1-Trichloroethane (TCE), a widely used and abused solvent, was investigated for its ability to produce physical dependence in mice. Cessation of 4 days of continuous inhalation of TCE (500-4000 ppm) resulted in a withdrawal syndrome characterized by handling-induced convulsions and increased susceptibility to pentylenetetrazol-induced convulsions. The severity of withdrawal convulsions was diminished by 30 to 60 min of reexposure to 2000 to 4000 ppm TCE or to the vapor of another widely used and abused solvent, toluene (1000-2000 ppm). Ethanol (1-2 g/kg), midazolam (0.3-1 mg/kg) and pentobarbital (30 mg/kg) were also effective in decreasing the withdrawal severity; however, chlorpromazine (3 mg/kg) and phenytoin (30 mg/kg) were without effects. These data suggest that TCE has the ability to produce physical dependence of the central nervous system depressant drug type. Taken together with other evidence for similarities in the pharmacological and behavioral effects of TCE and depressant drugs of abuse, these data support the hypothesis that the basis for TCE abuse may be its ability to produce ethanol- and depressant drug-like effects. PMID- 8437121 TI - Histamine releases norepinephrine in the paraventricular nucleus/anterior hypothalamus of the conscious rat. AB - These experiments evaluated norepinephrine (NE) release evoked by histamine (HA) in the paraventricular nucleus/anterior hypothalamic (PV/AH) region of conscious rats. In vivo microdialysis techniques were used to estimate extracellular NE concentrations in the PV/AH before, during and after perfusing the microdialysis probes with artificial cerebrospinal fluid containing HA (0, 1, 3 or 10 mg of HA per ml of artificial cerebrospinal fluid). Administration of HA through the microdialysis probe resulted in a significant, dose-related increase in dialysate NE concentration, which returned to control values after HA perfusion. Blood pressure and heart rate were not altered during perfusion with these concentrations of HA. The increase in NE was attenuated by administration of a specific H1 receptor antagonist, chlorpheniramine, but was not altered consistently by treatment with the H2 receptor antagonist, cimetidine. Furthermore, extracellular NE increased when perfusate contained the specific H1 receptor agonist, 2-thiazolyethylamine, but was not increased by similar administration of the H2 receptor agonist, dimaprit. These data demonstrate that HA releases NE in the PV/AH brain region of the conscious rat primarily by activation of H1 receptors. This finding supports an interaction between HA and NE neurons in the hypothalamus. PMID- 8437122 TI - Antagonist effects of beta-funaltrexamine and naloxonazine on alfentanil-induced antinociception and muscle rigidity in the rat. AB - Alfentanil is a potent and short-acting mu opioid agonist that produces both antinociceptive effects and muscle rigidity. In the present study, the susceptibility of alfentanil-induced antinociception and rigidity to antagonism by the selective mu antagonist beta-funaltrexamine and the selective mu-1 antagonist naloxonazine was examined. Alfentanil (37.7-150.0 micrograms/kg) produced a dose-dependent increase both in antinociception as measured by the warm-water tail-dip assay and in rigidity as measured by electromyographic recording of the gastrocnemius muscle. Both beta-funaltrexamine (10.0 and 20.0 mg/kg) and naloxonazine (7.5 and 15.0 mg/kg) produced dose-dependent and parallel rightward shifts in the alfentanil dose-effect curves for both antinociception and rigidity. Furthermore, the alfentanil dose-effect curves for antinociception and rigidity were shifted to the right to a similar degree by any given pretreatment. These results suggest that alfentanil-induced antinociception in the warm-water tail-dip test and rigidity are mediated by pharmacologically similar populations of opioid receptors. More specifically, these results suggest that mu-1 opioid receptors mediate both alfentanil-induced antinociception and rigidity. PMID- 8437123 TI - Effects of phencyclidine-type drugs in rats discriminating fentanyl from saline: pharmacological and behavioral characterization of intermediate levels of drug lever selection. AB - In rats trained to discriminate 0.04 mg/kg fentanyl from saline, phencyclidine (PCP) and the PCP-type drugs ketamine and (+/- )-5-methyl-10,11-dihydroxy-5H dibenzo(a,d)cyclohepten-5,10-imine produced effects that are usually referred to as partial generalization. Partial generalization could conceivably result from low efficacy actions at the receptor mediating the discriminative stimulus effects of the training drug. The PCP-type drugs produced maximum percentages of drug lever (DL) selection intermediate between those produced by the training conditions, but their curves relating dose to percentage of DL selection were not shallower than that of fentanyl. The PCP-type drugs decreased DL selection produced by the training dose of fentanyl, but there was no relationship between these antagonist effects and the DL selection produced by the PCP-type drugs when given alone. Naltrexone antagonized DL selection produced by fentanyl, but not that produced by the PCP-type drugs. The potency order of the PCP-type drugs to produce DL selection was in agreement with their relative affinities for PCP receptors, but not with those for morphine receptors. The intermediate levels of DL selection produced by the PCP-type drugs were associated with increased lever selection latencies and increased responding on the nonselected lever; this pattern of effects resembled the behavior of animals that had not yet acquired the discrimination. The results suggest that PCP-type drugs produce intermediate levels of drug-appropriate responding in fentanyl-trained rats through mechanisms involving not opioid receptors and partial generalization, but involving PCP receptors and performance deficits conceivably resulting from state dependency. Thus, the results stress the importance of a pharmacological and behavioral analysis of intermediate responding in drug discrimination to examine its validity as a measure of efficacy and of stimulus similarity. PMID- 8437124 TI - Inhibition of brain protein kinase C subtypes by lead. AB - Protein kinase C (PKC) is an important enzyme in mediating cellular signal transduction and neuronal plasticity. Extremely low concentrations (picomolar range) of Pb++ have been reported to activate partially purified PKC from rat brain (Markovac and Goldstein, 1988). However, the lead activation of PKC at such low concentrations is still a matter of discussion (Simons, 1989). To clarify this point, we have examined the lead effect on highly purified PKC subtypes. Pb++ was found to be a potent inhibitor for all three PKC subtypes (types I, II and III) with IC50 of 2 to 10 microM. Characterization of this lead inhibition of PKC suggests that 1) the inhibition is not due to the competition with Ca++, 2) the site of action of lead is on the catalytic domain of PKC, 3) the inhibition is not dependent on the mode of activation (phosphatidylserine/diacylglycerol vs. cis-unsaturated fatty acid) and 4) the inhibition is totally reversible. PMID- 8437125 TI - Effects of caffeine on cholinergic agonist- and K(+)-induced cytosolic Ca++ signals and secretion in porcine adrenal chromaffin cells. AB - A possible involvement of Ca(++)-induced Ca++ release mechanisms in muscarinic agonist-induced, extracellular Ca(++)-independent, catecholamine secretion in porcine adrenal chromaffin cells was examined. Caffeine was found to induce rapid increases in cytosolic Ca++ ([Ca++]in) in a ryanodine-sensitive manner. In addition, caffeine pretreatment inhibited methacholine (a selective muscarinic agonist)- and thapsigargin (thapsigargin depletes inositol 1,4,5-trisphosphate sensitive Ca++ pools)-induced increases in [Ca++]in as well as methacholine induced secretion. However, several lines of evidence suggest that Ca(++)-induced Ca++ release does not play a major role in methacholine-induced increases in [Ca++]in. Instead, the results are more compatible with the notion that Ins(1,4,5)P3 and caffeine activate Ca++ release from the same intracellular Ca++ pool, or that distinct Ca++ pools, if they exist, can equilibrate rapidly. Caffeine pretreatment was also observed to eliminate nicotinic responses but not elevated extracellular K(+)-induced responses, suggesting that caffeine blocks nicotinic receptor-channels. PMID- 8437126 TI - Pharmacokinetic and pharmacologic properties of antiuterotonic oxytocin analogs in the rat. AB - The pharmacologic and pharmacokinetic properties were evaluated in a series of antiuterotonic oxytocin analogs, modified at positions 1, 2, 4, 8 and, in one case, position 9 of the oxytocin (OT) molecule. [Mpa1,D Tyr2(Et),Val4,Orn8,desGly9]-OT, [Mpa1,Tyr2(Et),Val4,Orn8]-OT and [Mpa1,D Tyr2,Val4,Orn8]-OT displayed similar plasma clearance rates (Clps) using the constant infusion method in rats. Two analogs, [Mpa1,D-Tyr2(Et),Val4,Orn8]-OT and, particularly, [Mpa1,D-Tyr2(Et),Thr4,Orn8]-OT, were cleared at significantly higher rates compared with the others. [Mpa1, D-Tyr2(Et), Val4, Orn8]-OT and [Mpa1, D-Tyr2(Et), Thr4, Orn8, desGly9]-OT were most potent in eliciting a short term in vivo antiuterotonic effect, whereas the duration of effect was longest for [Mpa1, D-Tyr2, Val4, Orn8]-OT and [Mpa1, D-Tyr2(Et), Thr4, Orn8, desGly9]-OT. The Clp of [Mpa1, D-Tyr2, Val4, Orn8]-OT was similar regardless of the infusion rate. No relationship between antiuterotonic effect and Clp of the five peptides could be demonstrated, and no significant linear correlation between Clp and effect duration was found. The apparent volumes of distribution for the present analogs were 10-fold larger than the blood volume, a finding to be considered when measuring in vivo antagonistic activity. The 24-h urinary excretion ranged from 14.3 to 25.6% of the i.v. dose and was negatively correlated with peptide lipophilicity. It is concluded that, in addition to diverging pharmacologic properties, peptide analogs may differ markedly in kinetic parameters like Clp, volumes of distribution and urinary excretion despite minor molecular modifications. PMID- 8437127 TI - Differential effects of antimuscarinic agents on intestinal motility in the conscious dog. AB - In this study we investigated the effects of antimuscarinics with different selectivity on the intestinal migrating myoelectric complex (MMC) in five fasting, conscious dogs, chronically fitted with electrodes along the small bowel. Furthermore, we evaluated the chronotropic and mydriatic effects to assess the in vivo selectivity of the agents tested. Dose-response studies were performed with the following drugs administered i.v.: atropine, telenzepine (M1 antagonist), AF-DX 116 [11,2-(diethylamino)methyl-1-piperidinyl-acetyl-5,11 dihydro-6H-pyrido-2 ,3b- 1,4-benzodiazepine-6-one (M2 antagonist)] and 4 diphenylacetoxy-N- methylpiperidine methiodide (4-DAMP) (M3 antagonist). All the antimuscarinics tested dose-dependently increased the duration of the MMC period and inhibited spike activity, except low-dose telenzepine (3-10 nmol/kg), which shortened the MMC period and stimulated spike activity. High-dose telenzepine (> 100 nmol/kg) mimicked the inhibitory effect of atropine on the intestine. ED50 values for delay of MMC onset were 87,232, > 10,000 and 129 nmol/kg for atropine, telenzepine, AF-DX 116 and 4-DAMP, respectively. At doses lengthening the MMC period, atropine and 4-DAMP also induced tachycardia and mydriasis. At doses shortening the MMC period, telenzepine had no effect on pupil diameter or heart rate, except at the dose of 10 nmol/kg, which reduced heart rate. Finally, AF-DX 116, at doses inducing marked tachycardia, had a minor intestinal effect and no mydriatic effect. The present data are consistent with the hypothesis that both M1 and M3 receptors are involved in the regulation of the MMC: M1 receptors are probably located on an inhibitory pathway, whereas M3 receptors mediate excitatory stimuli.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437128 TI - Pharmacological specificity of the discriminative stimulus properties of 2-amino 4,5-(1,2-cyclohexyl)-7-phosphono-heptanoic acid (NPC 12626), a competitive N methyl-D-aspartate receptor antagonist. AB - A drug discrimination based upon the competitive N-methyl-D-aspartate (NMDA) antagonist 2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid (NPC 12626) was assessed for pharmacological specificity. Adult male Sprague-Dawley rats were trained to discriminate 20 mg/kg i.p. of NPC 12626 from saline under a standard two-lever fixed ratio 32 schedule of food reinforcement. Stimulus generalization tests were conducted to examine the similarities and differences between NPC 12626, its active (2R,4R,5S) enantiomer NPC 17742, other competitive and noncompetitive NMDA antagonists and a number of drugs representative of other classes. During test sessions, the competitive NMDA antagonists NPC 12626, CGS 19755, [1-(cis-2-carboxypiperidine-4-yl)- methyl-1-phosphonic acid], NPC 17742, CSP 37849 [DL-(E)-2-amino-4-methyl-5-phosphono-3-pen-tenoic acid] and CPPene [D-3 (2-carboxypiperazin-4-yl)-1-propenyl-1-phosphonic acid] all completely substituted for the training dose of NPC 12626 with ED50 values of 18.1, 2.3, 2.1, 0.8 and 0.8 mg/kg, respectively. In contrast, drugs that failed to substitute for NPC 12626 included (+)-amphetamine, baclofen, chlorpromazine, dextromethorphan, diazepam, dizocilpine (MK-801), imipramine, (-) ketocyclazocine, L-N6-phenylisopropyladenosine, methocarbamol, morphine, muscimol, phenytoin, physostigmine and valproate. These results provide evidence that the NPC 12626 discriminative stimulus is unique and specific, shared fully only by its active enantiomer NPC 17742 and other competitive NMDA antagonists. This specificity provides further support for the hypothesis of NMDA receptor mediation of NPC 12626 discrimination, and suggests that this is a useful model to evaluate behavioral effects of competitive NMDA antagonists. PMID- 8437129 TI - Testosterone modulation of N-acetylation in mouse kidney. AB - N-acetylation participates in the biotransformation of hydrazine drugs and arylamine carcinogens to cytotoxic and carcinogenic products. Differences in acetylation capacity expressed in several mammalian species, including humans and mice, are associated with differences in toxicity and carcinogenicity from these chemicals. The present study examines the influence of genotype, age and sex on kidney N-acetyltransferase (NAT) activity in C57BL/6J (B6) and A/J inbred mouse strains using p-amino-benzoic acid (PABA) as a substrate. There were no strain differences in kidney PABA NAT activity. However, within these strains, males have greater kidney NAT activity than females. A 2-fold increase in kidney NAT activity of males was evident by 30 days postnatally and persisted into maturity (> 200 days after birth), whereas the kidney NAT activity of females remained unchanged. Castration reduced male kidney NAT to female levels, whereas testosterone replacement restored original levels of activity. Ovariectomized females exhibited the same enzyme activity as intact females. Testosterone increased kidney NAT activity in females, but not in intact males. Estradiol decreased kidney NAT in males, but had no effect on female NAT activity. The data suggest that the increase in kidney NAT activity in male mice that accompanies development is under androgenic control. This idea is further supported by our finding that the kidney NAT activity of androgen-insensitive tfm/y mice is significantly less than the activity of either females or males sharing the same genetic background. These observations may explain, in part, the higher susceptibility of male mice to 2-acetylaminofluorene mutagenicity and carcinogenicity. PMID- 8437130 TI - Kinetics of drug action in disease states. XLI. Effect of adrenalectomy on the hypnotic activity of phenobarbital, the neurotoxicity of theophylline and pain sensitivity in rats. AB - The purpose of this investigation was to determine the effects of adrenalectomy and adrenalectomy with corticosterone replacement on pain sensitivity and on the pharmacodynamics of a central nervous system depressant, phenobarbital, and a central nervous system stimulant, theophylline. Male Sprague-Dawley rats, bilaterally adrenalectomized, were maintained on normal saline solution or normal saline solution with corticosterone, 160 micrograms/ml, as drinking water for 9 or 11 days. Sham-operated animals served as normal controls. They were then tested for pain sensitivity by the tail-flick method. Phenobarbital or theophylline was infused i.v. slowly until the onset of loss of righting reflex or of maximal seizures, respectively. Samples of cerebrospinal fluid (CSF), blood (for serum) and the brain were obtained at that time and assayed for phenobarbital or theophylline by high-performance liquid chromatography. Compared to the controls, the adrenalectomized rats required a smaller dose and lower concentrations of phenobarbital in serum, brain and CSF (12% decrease) to produce loss of righting reflex. The opposite effect was observed in adrenalectomized rats supplemented with corticosterone. Adrenalectomy had no apparent effect on the dose and the serum, brain and CSF concentrations of theophylline at the onset of maximal seizures whereas adrenalectomized, corticosterone-supplemented animals required a larger dose and higher concentrations (17% increase in CSF) of theophylline than controls to produce seizures. Tail-flick latency was slightly (19%) but statistically significantly reduced in adrenalectomized rats and lengthened (18%) in adrenalectomized, corticosterone-supplemented animals. PMID- 8437131 TI - Distributional transport kinetics of zidovudine between plasma and brain extracellular fluid/cerebrospinal fluid in the rabbit: investigation of the inhibitory effect of probenecid utilizing microdialysis. AB - The effect of probenecid (PBD) on the distributional transport of zidovudine (AZT) between plasma, cerebrospinal fluid (CSF) and brain extracellular fluid (ECF) was investigated by using microdialysis. New Zealand White rabbits received AZT, in a crossover design, during control and treatment periods. PBD was coadministered at one of two rates. One additional study involved a repeated control to investigate the possible existence of a period effect. In the low- and high-dose treatment groups, PBD decreased the total body clearance of AZT by 47.7 +/- 8.9 and 51.7 +/- 9.7%, respectively. PBD also decreased the clearance of AZT from CSF and thalamus ECF, prolonging the half-lives of AZT disappearance from the brain. Additionally, PBD elevated the AZT area under the concentration-time curve in the ventricular CSF 3- to 5-fold and the area under the thalamic ECF concentration-time curve by 5- to 6-fold, whereas the area under the plasma concentration-time curve increased only 2-fold. During PBD treatment the ratio area under the thalamic ECF concentration-time curve/area under the ventricular CSF concentration-time curve approached unity. These results provide evidence that AZT is actively transported outwardly across the CSF- and brain ECF-blood barriers, and this transport system is sensitive to PBD. A pharmacokinetic model that considers the effect of PBD on the AZT clearance from brain to plasma suggests that 73% of this pathway is subject to competitive inhibition by PBD. PMID- 8437132 TI - Antigen-mediated pulmonary eosinophilia in immunoglobulin G1-sensitized guinea pigs: eosinophil peroxidase as a simple specific marker for detecting eosinophils in bronchoalveolar lavage fluid. AB - Eosinophil peroxidase (EPO) has been used previously to detect the number of eosinophils in the peritoneal exudate and bone marrow of mice. The present study was undertaken to determine 1) whether EPO activity may provide a measure of a change in eosinophils in bronchoalveolar lavage fluid (BALF) of guinea pigs, 2) whether immunoglobulin (Ig)G1 could play a role in pulmonary eosinophilia and 3) effects of pharmacological agents on the EPO response in an IgG1 passively sensitized animal model. The activity of EPO was assessed by the ability of cell lysates (0.1% Triton-100 treatment) to oxidize 1 mM o-phenylenediamine in the presence of 1 mM H2O2 for 5 min at 22 degrees C. The enzyme activity was found to be eosinophil dependent, inhibited by the EPO inhibitor 3-amino-1,2,4-triazole (IC50 = approximately 0.1 mM) and relatively resistant to heat treatment (no loss of activity after 2-hr preincubation at 56 degrees C). To determine antigen dependent eosinophil and EPO responses, guinea pigs were passively sensitized i.p. with 0.5 mg/kg of an affinity-purified antiovalbumin (OA) IgG1. Two to 3 days later, the sensitized animals were injected with pyrilamine (5 mg/kg, i.p.) before OA aerosol challenge. Aerosolized OA (0.1%) caused a significant increase in both eosinophil number and EPO activity in BALF of sensitized guinea pigs at 18 to 24 hr post-challenge. At a given concentration of aerosolized OA, the enzyme activity increased as a function of the antibody dose and time post-OA challenge.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437133 TI - Episodic excretion of ethanol during chronic intragastric ethanol infusion in the male rat: continuous vs. cyclic ethanol and nutrient infusions. AB - Continuous intragastric infusion of ethanol has been reported to result in episodic daily blood alcohol concentrations in male rats (Tsukamoto et al., 1985). We have used a total enteral nutrition (TEN) model to study the effects of chronic alcohol exposure on blood and urine alcohol concentrations in adult male Sprague Dawley rats (300 g). Two TEN models were studied: 1) the continuous model in which a complete diet was infused i.g. for 24 h/day; or 2) the cyclic model in which TEN was infused intragastrically for 12 h/day (i.e., only during the dark phase of the lighting cycle). In the continuous model, blood alcohol concentrations (BACs) were determined at 0900 h each morning and were found to vary from day to day in an episodic fashion, with values ranging from less than 10 mg/dl to greater than 500 mg/dl. The urine alcohol concentrations (UACs) were also episodic and closely tracked those of serum, such that the 24-h UACs were excellent predictors of the BACs taken at 0900 h. Both BACs and UACs increased from values below 10 mg/dl to greater than 500 mg/dl, and then decreased back to below 10 mg/dl with a mean peak-to-peak interval of 6 +/- 0.9 days. In the cyclic model, daily UACs were also episodic (i.e., had a daily variation) and very closely resembled those of the continuous model. We have proposed that ethanol metabolism during experimental intragastric ethanol infusion in the rat occurs via a system characterized by time-dependent pharmacokinetics. PMID- 8437134 TI - Cytochrome P450 CYP 2E1 induction during chronic alcohol exposure occurs by a two step mechanism associated with blood alcohol concentrations in rats. AB - Intragastric infusion of ethanol to male rats as part of a system of total enteral nutrition allows chronic ethanol treatment without the nutritional and feeding problems associated with traditional liquid diets. Even though ethanol was infused at a constant rate 24 h a day, blood alcohol concentrations were observed to cycle over a 5- to 7-day period from values less than 10 mg/dl to greater than 400 mg/dl. Examination of the hepatic microsomal mono-oxygenase system in animals chronically treated with ethanol using this model revealed variable induction of cytochrome P450 CYP 2E1, the principal component of the microsomal ethanol oxidizing system. Correlations were observed between urine alcohol concentrations (UACs) and 1) the level of expression of CYP 2E1 mRNA in Northern blot analysis, 2) the level of CYP 2E1 apoprotein in Western blot analysis and, 3) microsomal p-nitrophenol (PNP) hydroxylation. The data from ethanol-treated animals were expressed as low UAC group (UACs < 200 mg/dl) and a high UAC group (UACs > 300 mg/dl) and compared to total enteral nutrition controls. In the low UAC group, a 6- to 7-fold induction in microsomal PNP hydroxylase (a CYP 2E1-dependent activity) was accompanied by a 4- to 5-fold increase in CYP 2E1 apoprotein, but no increase in CYP 2E1 mRNA levels. In contrast, in the high UAC group, induction of PNP hydroxylase was 15- to 16-fold, induction of CYP 2E1 apoprotein was 12- to 13-fold and CYP 2E1 mRNA was elevated 5- to 6-fold.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437135 TI - Distinct signal transduction pathways for angiotensin-II in guinea pig gastric smooth muscle: differential blockade by indomethacin and tyrosine kinase inhibitors. AB - In guinea pig gastric longitudinal (LM) and circular (CM) muscle strips, angiotensin-II (Ang-II) caused a concentration-dependent contraction that required extracellular calcium and that could not be attributed to the secondary release of agonists from neural elements. Contractions in both the LM and CM were blocked by the Ang-II AT1 receptor antagonist, Losartan (DuP 753, pA2 9.1) but not by the AT2 antagonist, PD 123319. However, in the LM preparation, indomethacin (3 microM) blocked Ang-II-mediated contraction, whereas in the CM contraction was resistant to indomethacin. Contractions caused by Ang-II in the CM preparations were also unaffected by inhibitors of leukotriene biosynthesis, but were partially (58%) inhibited by the cytochrome P450 monooxygenase inhibitor, ketoconazole. The diacylglycerol lipase inhibitor, U57,908, at a concentration (20 microM) that completely blocked the contractile action of epidermal growth factor in the LM, caused a substantial inhibition of Ang-II mediated contraction in both the LM (55% inhibition) and CM (75% inhibition). The phospholipase A2 inhibitor, mepacrine caused a modest inhibition (24%) of contraction in both preparations. In the presence of U57,908, mepacrine further inhibited contraction caused by Ang-II in the LM preparation. The tyrosine kinase (YK) inhibitors, genistein and tyrphostin (RG 50864) selectively and completely blocked Ang-II-mediated contraction in the LM, without affecting contractions caused by carbachol and bradykinin. In the CM preparation, the two YK inhibitors were selective, but only partially (40-60%) blocked Ang-II-mediated contraction, without affecting contractions caused by bradykinin and carbachol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437137 TI - Determinants of denial: a study of alcoholics. AB - 1. Although denial may at times operate as a coping mechanism used by alcoholics in an attempt to adapt to a perceived threatening environment, it can be a detriment to recovery. 2. The assessment of denial can be laborious because of the various aspects of denial and the obscure manner in which it can manifest itself. 3. To facilitate the assessment process, the authors have undertaken a study to operationalize denial by its observable behaviors. PMID- 8437136 TI - [3H]quinpirole binding to putative D2 and D3 dopamine receptors in rat brain and pituitary gland: a quantitative autoradiographic study. AB - The putative D2 dopamine receptor agonist quinpirole (LY 171,555) has been extensively used in a variety of in vivo and in vitro studies of D2 receptor mediated effects and may have even higher affinity for the recently described D3 dopamine receptor. In the present study, conditions for autoradiographic visualization of [3H]quinpirole-labeled D2-like dopamine receptors were optimized and binding to slide-mounted sections was characterized with respect to pharmacology, guanine nucleotide sensitivity and regional distribution. The pharmacological profile of [3H]quinpirole binding in slide-mounted brain sections was: (+/-)-2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene > or = quinpirole > dopamine for putative dopamine agonists; spiperone > (+)-butaclamol > (-) sulpiride > SCH 23390 >> cinanserin > (-)-butaclamol for antagonists. [3H]Quinpirole binding was decreased in the presence of guanine nucleotides in most brain regions except in the islands of Calleja and the molecular layer of cerebellar lobules 9 and 10. The regional distribution of [3H]quinpirole binding sites roughly paralleled the distribution of [3H]-(-)-sulpiride binding sites, with greatest densities present in the olfactory bulb glomerular layer, islands of Calleja, pituitary intermediate lobe, caudate/putamen, olfactory tubercles and nucleus accumbens. However, significantly greater densities of [3H]quinpirole binding than [3H]-(-)-sulpiride binding were observed in the molecular layer of cerebellar lobules 9 and 10, the islands of Calleja and olfactory bulb glomerular layer in concordance with the recently reported distribution of D3 receptor mRNA in these brain regions. Higher concentrations of [3H]quinpirole binding were also observed in the dorsomedial caudate and pituitary intermediate lobe. These data indicate the utility of [3H]quinpirole to label D3 as well as D2 dopamine receptors. PMID- 8437138 TI - Technique integration. Therapeutic touch and theory-based mental health nursing. AB - Acceptance of therapeutic touch (TT) by the nursing community has become widespread. Nurses are advancing the pioneering work of Krieger (1973) through practice, research, education, and, most recently, through the development of theory-based nursing practice. The purpose of this article is to contribute to the development of theory-based nursing practice by introducing integration of TT with mental health nursing approaches. The Science of Unitary Human Beings (Rogers, 1986) is used to explain the relationship between TT and mental health nursing practice. The use of TT in practice is demonstrated through case examples from experiences with students and clients. PMID- 8437139 TI - Debriefing: from military origin to therapeutic application. AB - 1. The objective of the debriefing process is the prevention of post-traumatic stress disorder (PTSD). Risk factors for PTSD can be classified into three categories: premorbid personality, the environment, and the trauma itself. 2. Nurses are in a position to intervene using debriefing at primary, secondary, and tertiary levels of prevention. 3. Debriefing, individually and in groups, is an effective intervention in preventing the adverse reactions incurred by a traumatic stressor. The use of a debriefing model counteracts the tendency to suppress the powerfully affective component of the traumatic experience. PMID- 8437140 TI - Recognizing multiple personality disorder. AB - 1. It currently takes an average of 5 to 7 years and repeated hospitalizations for a person with multiple personality disorder (MPD) to be accurately diagnosed. 2. Reasons for misdiagnosis include the assumption that MPD is rare, the complex polysymptomatic presentation of the disorder, and failure of standard psychiatric histories to elicit pertinent diagnostic information. 3. Nurses are often the first to observe the behavioral, clinical, and physiological symptoms associated with MPD. 4. It is important to include questions that will elicit pertinent diagnostic information in the nursing history and assessment. As nurses become more adept at recognizing this disorder, individuals with MPD will receive more prompt and appropriate treatment. PMID- 8437141 TI - What are the warning signs for suicidal adolescents? PMID- 8437142 TI - Unrealistic identity. PMID- 8437143 TI - Home mental health care developed for AIDS patients. PMID- 8437144 TI - Waking from a fog. PMID- 8437145 TI - Otolaryngological indicator operations: one year's experience. AB - One year's experience of otolaryngological indicator operations is presented. Of 59 myringoplasties, 47 (79%) were successful; trainees performed 44 (74%) of the procedures. Seventy patients undergoing septal surgery reported significant improvements in nasal obstruction (P < 0.001), catarrh and facial pain (P < 0.005). Seventeen laryngectomies were performed for stage III and IV disease. The median operative time of 3.1 h rose to 5.1 h with a concomitant neck dissection. Eleven complications ensued, and the median stay for an uncomplicated laryngectomy was 16 days and 30 days following complications. Forty-one parotidectomies, 19 submandibular gland excisions and 10 ductal procedures were performed with 5 wound complications and 5 minor temporary facial nerve weaknesses. We have established a baseline for comparison of our practice with others and concluded that septal surgery gives good symptomatic relief, trainees perform reasonable numbers of myringoplasties, and improvements remain to be made in our outpatient septal surgery data collection. PMID- 8437146 TI - The surgical management and outcome of oesophageal cancer in Khartoum. AB - One hundred and one patients with oesophageal cancer seen at a surgical firm in Khartoum were studied retrospectively. An increase in the relative frequency of the disease is noted (4.6%). Sixty-nine patients (69%) were explored and 61 (87%) of them had resection (all had locally invasive tumours). All had an Ivor Lewis type of resection using a stomach tube through the right side of the chest. The postoperative mortality after 30 days was 27.8% (n = 17) which dropped to 14% towards the end of the series (one death in 7 cases). The commonest cause of death in the surgical group was failure to recover fully from anaesthesia (n = 5). In 30 patients who could be traced for a minimum period of 12 months, 18 patients (64%) survived for 1 year and 12 patients for 2 years. Fifteen patients have been on follow-up for less than 12 months and all are doing well; 16 patients could not be traced. PMID- 8437147 TI - Blunt abdominal trauma--injury assessment in relation to early surgery. AB - One hundred and thirteen patients sustaining blunt abdominal trauma over a 24 month period were retrospectively divided into three groups to assess parameters of three diagnostic methods and the time-lapse before implementing surgical treatment. Diagnosis was based in group A patients (n = 20) on physical findings, plain radiology, and blood and urine examinations. Diagnostic methods in group B patients (n = 35) and in group C patients (n = 58) were as in group A but with the addition of diagnostic peritoneal lavage (DPL) in group B or with the addition of diagnostic abdominal ultrasonography (DAU) in group C. Sixty-five patients underwent abdominal exploration. The time-lag from commencement of examination to surgery was 332.33 +/- 48.90 min, 251.82 +/- 29.08 min and 570.89 +/- 133.80 min respectively in groups A, B and C. It was significantly shorter in group B compared with group C (P = 0.03). DPL had a sensitivity of 95%, a specificity of 81% and an accuracy of 89% whilst DAU had a sensitivity of 79%, a specificity of 85% and an accuracy of 83% in detecting significant injury. The conclusion is that DPL in combination with DAU would facilitate early assessment and treatment of intra-abdominal injuries. PMID- 8437148 TI - Smooth muscle tumours of the stomach: clinicopathological aspects. AB - From 1984 to 1989 the clinicopathological aspects of 21 patients with smooth muscle tumours of the stomach were reviewed. Ten patients had leiomyomas: 7 males, 3 females, average age 53 +/- 8 years. Four out of seven leiomyomas presenting with haematemesis were diagnosed correctly by an endoscopist but biopsy was positive in only two patients. Three leiomyomas were found incidently at laparotomy, and a total of nine leiomyomas were resected with a cuff of normal stomach. Their size ranged from 2 to 20 cm. All patients who underwent local resection are alive. Eight patients had leiomyosarcomata: 3 males, 5 females, average age 62 +/- 9 years. Six of these patients had an epigastric mass and four had haematemesis or melaena. The remaining patient in this group presented with dysphagia. Seven of these patients, who had no evidence of metastatic disease, underwent exploratory laparotomy. In four, palliative resections of the stomach and distal oesophagus were performed. In two, exogastric lesions involving colon and liver respectively were resected en bloc with a cuff of stomach. In one, biopsy alone was carried out. Two patients in this group are alive 1 and 2 years following surgery. Adjuvant treatment was not given to any of our patients. The remaining three tumours comprised a smooth muscle tumour of undetermined malignant potential whose clinical behaviour was unpredictable, and two leiomyoblastomas which mimicked malignant tumours in their presentation. PMID- 8437149 TI - The case for formal stratification analysis when prescribing deep vein thrombosis prophylaxis. AB - Postoperative deep vein thrombosis (DVT) is common following general and orthopaedic surgery. Certain factors are known to increase the risk of DVT. To ascertain how surgeons use these factors to assess DVT risk and modify their DVT prophylaxis for individual cases, we circulated a questionnaire to 100 general and 200 orthopaedic surgeons. We inquired about whether DVT prophylaxis was used, and what risk factors were recognized, and we asked the surgeons to ascribe a level of DVT risk for five imaginary cases. All surgeons claimed to use prophylaxis. Most surgeons were largely aware of the accepted risk factors. There was, however, no consensus in allocating level of risk to individual imaginary cases. In conclusion, in spite of being aware of risk factors, similar patients are being dealt with in widely different ways by different clinicians. Therefore, we feel it is important to formally assess each individual patient's DVT risk and prescribe prophylaxis accordingly. PMID- 8437150 TI - The use of the Nd-YAG laser in the treatment of rectal carcinoma and adenoma. AB - Although radical excision remains the treatment of choice for rectal carcinoma and large rectal polyps, laser treatment of such tumours in patients unfit for surgery, as well as for those fit patients with small sessile rectal polyps, is a valid therapeutic option. In the present series 24 patients (16 males and 8 females; median age 78.5 years, range 59-91) had laser treatment--six for rectal carcinoma and 18 for benign rectal polyps. A Nd-YAG laser was used to treat all patients using either a rigid operating or a flexible sigmoidscope to gain access to the tumour. Debulking of large tumours with the diathermy snare before laser treatment was very helpful. In this series 50 to 70 watts of power for 2 to 5 s were used. Total doses of laser energy administered ranged from 414 to 26,117 joules and depended on the initial tumour size and also the amount of tumour that could be removed during preliminary debulking. There were no immediate post treatment complications but one patient developed a rectovaginal fistula 3 months after laser treatment. Two carcinomas were completely ablated by laser treatment and the other four patients with rectal carcinoma had fair to excellent palliation. All but one of the polyps were completely cleared by laser therapy. Laser therapy seems superior to simple fulguration as three patients who had repeated fulgurations for large polyps without much success had their polyps dramatically improved by laser treatment. PMID- 8437151 TI - Crush injuries of the chest. An historical perspective in a single unit. AB - The management of crushed chest injuries in the 1950s was unsatisfactory. A survey of these injuries in south-east Scotland in 1955-60 showed a mortality of 76%. The introduction of intermittent positive pressure ventilation carried out in a special unit produced a dramatic improvement in outcome with mortality reduced to 16% in a reported series in 1961-65. Two further similar series of crushed chest injuries treated in the same unit in 1977-81 and 1988-91 are now described. Overall mortality rates have remained the same at 17% and 16%. Details of injuries, management and causes of death are given. It is concluded that intermittent positive pressure ventilation remains the mainstay of treatment and that further improvement in results will be difficult to obtain. PMID- 8437152 TI - Bupivacaine infiltration after haemorrhoidectomy. AB - The effect of a locally infiltrated solution of bupivacaine was studied in 30 patients undergoing haemorrhoidectomy. A standard Milligan-Morgan haemorrhoidectomy, with preoperative infiltration of adrenaline solution (1:200,000), was performed. The patients were randomized to receive local four quadrant perianal infiltration of 20 ml of 0.5% bupivacaine or normal saline. Analgesia was available on demand postoperatively. There was no significant difference between the groups with respect to visual analogue pain scores, analgesic requirement, time to first bowel action or duration of hospital stay. Bupivacaine as a local infiltration in this situation does not confer analgesic effect into the postoperative period. PMID- 8437153 TI - Prolonged dysphagia after highly selective vagotomy. PMID- 8437154 TI - Persistent perineal sinus: treatment by transposition rhomboid flap. PMID- 8437155 TI - Skin grafting to the anal canal for the treatment of mucocutaneous anal stricture. PMID- 8437156 TI - Laparoscopic exploration of the common bile duct: a training model. PMID- 8437157 TI - Multimodality treatment in the management of locally advanced breast cancer. AB - Forty-two patients with locally advanced breast cancer were treated with multimodality therapy comprising neoadjuvant chemotherapy (cyclophosphamide, vincristine, doxorubicin and prednisolone) and radiotherapy to the breast and lymph-draining areas, followed by tamoxifen and then selective surgery. The objective response rate (UICC criteria) of the primary tumours to chemotherapy alone was 72%, which increased to 83% following radiotherapy. The patients have been followed up for 13-56 months and the probability of local control at 36 months was 0.83. The probabilities of distant disease-free survival and overall survival were 0.50 and 0.65 respectively, at 36 months. However, if the patients' breast cancers had shown a response to chemotherapy/radiotherapy then the distant disease-free survival and overall survival of these subgroups of patients were 0.61 and 0.83 respectively, at 36 months. Toxicity included nausea, vomiting, alopecia, and peripheral neuropathies (two patients), but with no episodes of severe infection or bleeding. This multimodality therapy has achieved good local control and satisfactory overall and distant disease-free survivals with excellent patient compliance. PMID- 8437158 TI - Tracking change in the patterns of parental smoking. AB - This study examined the prevalence and predictors of parental smoking in a representative sample of mothers and fathers. The results showed that in this New Zealand sample approximately 38% of mothers and 43% of fathers were smokers, and that proportionally more fathers than mothers were ex-smokers. The pattern of maternal smoking was relatively less stable, showing a rate of increase over the first 2-year period and an equivalent rate over the second period for those who started or resumed smoking compared to those who stopped smoking. Predictors of maternal smoking groups included level of educational qualifications, number of changes of residence, personality (extraversion and neuroticism scores) and being a young mother. Predictors of paternal smoking groups from a smaller range of background variables included level of educational qualifications, socio-economic status and age. The measures did not satisfactorily differentiate smokers who decreased their level of smoking from those who increased their level of smoking and those who continued to smoke or not to smoke. PMID- 8437159 TI - Training of environmental health officers in Anglophone west Africa: how adequate for environmental monitoring? AB - There is concern that the curriculum for training Environmental Health Officers (EHO) in Anglophone English speaking West Africa grossly lags behind the skills needed by sanitarians in the sub-region to cope with the challenge of environmental monitoring/control. This paper examines in detail the existing curriculum for the training of EHOs at the diploma and degree levels in the sub region and observes that both curricula lack sufficient credit weight to impart the desired skills to perform the highly scientific task of environmental monitoring. Suggestions are made on ways and means of enhancing the professional education of EHOs in the sub-region. The paper contends that the situation places sanitarians in the sub-region at a serious academic handicap as many universities are reluctant to accept them for further studies in related fields. PMID- 8437160 TI - Writing: an educational and satisfying process. PMID- 8437161 TI - Managing fire safety in residential homes. PMID- 8437162 TI - How do potentially-toxic chemicals get into drinking water? PMID- 8437164 TI - The way forward with new medical and social developments in epilepsy. PMID- 8437163 TI - The health professions in 1992--The European challenge: the International Federation of Environmental Health. PMID- 8437165 TI - Health of the nation: way forward in sexual health. AB - Sexual health is a wide concept encompassing education, health promotion and disease prevention, diagnosis and management of sexually transmitted diseases, screening and counselling for HIV antibodies, management of HIV infected patients, family planning, termination of pregnancy, psychosexual counselling, prevention of cervical and lower genital tract cancers, and sexual abuse. Implementation of The Health of the Nation (1992) will include assessing the current situation, views, alliances and interventions, need for research and development and within alliances setting challenging but achievable targets. The Health of the Nation includes a target for gonorrhoea which is a surrogate for partner change, sexually transmitted diseases in general and HIV infection, and a target for conceptions among those under 16 years of age. These targets need to be adjusted locally and may be staged. All interventions to achieve these targets must be available. Implementation of The Health of the Nation to achieve the main objectives which are to reduce the incidence of HIV infection and other sexually transmitted diseases as well as reducing the number of unwanted pregnancies and provision of effective family planning services will be challenging but sexual health gain will be well worthwhile. PMID- 8437166 TI - Smoking in schools. PMID- 8437167 TI - Food, health, a better life. PMID- 8437168 TI - Hypnotism curse or cure--October 1992. PMID- 8437169 TI - Hypnotism curse or cure--October 1992. PMID- 8437170 TI - Albendazole--newer therapy for neurocysticercosis. PMID- 8437171 TI - Pediculosis pubis: a surrogate marker for sexually transmitted diseases. AB - A review of all the patients diagnosed to have Pediculosis pubis (P pubis) during a 2 year period 1989-1991 was carried out. They constituted the index group and were compared with 140 consecutive patients seen during the month of June 1990, who served as controls. Both groups were comparable with respect to age and use of modern contraception. Coexisting sexually transmitted diseases (STDs) were found in 37% of the index group. Incidence of STDs was 51% among the controls. In the preceding 3 months, patients in the index group had significantly more sexual partners p < 0.005. These findings emphasize the need to offer full STD screening and health education to sexually active people who present with P pubis. PMID- 8437172 TI - Awareness, knowledge and perceptions of restaurateurs about proposed smoking restrictions in Johannesburg restaurants. AB - 35 Johannesburg restaurateurs in randomly selected restaurants were interviewed by telephone to assess their awareness, knowledge and attitudes to proposed smoking restrictions in restaurants. The response rate was 78%. The 89% awareness of proposed legislation was gained mainly from newspapers but only 29% of these respondents knew the correct details. The majority of respondents believed that there should be separate areas for smokers and non-smokers. However, 64% of respondents anticipated that their business would be affected and 55% anticipated implementation problems. The real and unfounded problems recorded from this essential informant group contributed to the amendment of the legislation and the development of educational material for Johannesburg restaurateurs. PMID- 8437173 TI - Functional endoscopic sinus surgery in children. AB - During the last decade, the usefulness of functional endoscopic sinus surgery (FESS) has been clearly demonstrated in adult patients. Several recent studies have described the use of FESS in children. Most of the patients in these earlier studies have been school age or older. This paper will examine the follow-up of 44 children treated using FESS. The children's ages ranged from 14 months to 13 years with a mean age of 54.5 months. Thirty-three of the children were less than 6 years of age with a mean age of 35.3 months. Follow-up after surgery varied from 1 to 21 months with a mean of 7.4 months. There were no major surgical or anesthetic complications noted during the initial procedure or at the follow-up debridement. Overall the children did well, with 86% showing improvement. It appears that FESS can be helpful for even young children with chronic sinusitis. PMID- 8437174 TI - Effects of hypertonic and isotonic fluid infusion on the flash evoked potential in rats: hemorrhage, resuscitation, and hypernatremia. AB - In resuscitation from hemorrhagic shock, very small volumes of hypertonic saline (HS) improve blood pressure while reducing intracranial pressure and edema formation. The effects of hypertonic resuscitation fluids and hypernatremia on electrophysiologic brain function have not been studied. The present study was done in two parts. First we examined the effects of hemorrhagic shock and resuscitation with either 7.5% HS or lactated Ringer's (LR) solution on the flash evoked potential (FEP). Rats were bled to a mean arterial pressure (MAP) of 35 mm Hg for 1 hour, then resuscitated with HS (n = 10) or LR (n = 10) to a MAP of 80 mm Hg for another hour. Resuscitation required 3.8 +/- 0.5 mL/kg HS and 42.9 +/- 7.5 mL/kg LR (p < 0.05). During hemorrhage, FEP latencies increased and amplitudes decreased. During resuscitation, these variables returned toward baseline values. There were no significant differences between groups, although HS tended to restore the FEP better than LR. We next examined the effects on the FEP of hypernatremia and hyperosmolarity produced by two different hyperosmotic fluids. Over a 1-hour period, 16 mL/kg HS (n = 8), 16 mL/kg IsoSal (4.5% saline, 5.9% glucose, 6.4% mixed amino acids; n = 8), or 40 mL/kg LR (n = 8) was infused into normovolemic rats. Plasma sodium levels increased in both hyperosmotic groups (baseline = 145.2 +/- 0.7 mEq/L; after infusion, HS = 202.4 +/- 9.8 mEq/L, IsoSal = 163.3 +/- 4.2 mEq/L; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437175 TI - Biomechanics of abdominal injuries by armrest loading. AB - Anesthetized pigs were exposed to impact against a padded side interior that included an armrest with either a SOFT or STIFF crush characteristic. The purpose was to assess liver and spleen injury under specific impact conditions. The STIFF armrest resulted in severe abdominal and thoracic injury in five side-impact animal tests. Injuries of the liver and spleen included deep lacerations, tears of major hepatic arteries and veins, and serious hemoperitoneum. The injuries averaged AIS = 4. In contrast, five animals exposed to the SOFT armrest design experienced injuries of lower severity than any animal in the STIFF armrest exposures (p < 0.005). The average injury was AIS = 2. The STIFF armrest protruded into the abdomen and showed little sign of deformation with abdominal loading. This situation is consistent with the occurrence of lacerations at hepatic junctions and between lobes, and displaced rib fractures in several cases. The SOFT armrests crushed fully in each test, indicating that abdominal compression was lower and was limited by armrest deformation. PMID- 8437177 TI - Is helmet use beneficial to motorcyclists? AB - This study included 83 motorcyclists, helmeted and nonhelmeted, involved in crashes. All these patients were flown to a major trauma center in the Northeast (Hartford Hospital, Connecticut) directly from the scene by a helicopter ambulance service (LifeStar). The study showed that the majority of these patients were male and under the age of 30 years. Twenty-seven had blood alcohol levels above the legal limit. Sixty-nine percent were nonhelmeted and, statistically, a significant number in this category had a Glasgow Coma Scale (GCS) score of 8 or under. Cervical spine injuries were discovered in only six patients. Nine of the ten patients declared dead on arrival (DOA) were nonhelmeted. We conclude that helmets provide protection and certainly do not increase the incidence of cervical spine injuries. PMID- 8437176 TI - A retrospective cohort study of seatbelt use and pregnancy outcome after a motor vehicle crash. AB - To determine the effect of seatbelt use on pregnancy outcome we conducted a population-based retrospective cohort study of pregnant women (20 weeks' gestation or more) involved in motor vehicle collisions. Birth and fetal death certificates were obtained for 1243 restrained and 1349 unrestrained pregnant women involved in police-investigated motor vehicle crashes from 1980 through 1988. Unrestrained pregnant women drivers were 1.9 times more likely to have a low birth weight baby (95% confidence intervals = 1.2, 2.9) and 2.3 times more likely to give birth within 48 hours after the motor vehicle crash (95% confidence intervals = 1.1, 4.8) than restrained pregnant women drivers after adjusting for age and gestational age at crash. Although a trend for an increased risk of fetal deaths was observed among unrestrained women, too few fetal deaths occurred to accurately describe any association with restraint status. This study provides reassurance that the current recommendations on use of seatbelts by pregnant women are appropriate and should be continued. PMID- 8437178 TI - An analysis of accidental free falls from a height: the 'spring break' syndrome. AB - Vertical deceleration injuries represent a distinct form of urban blunt trauma. Mechanisms of injury differ from those of horizontal vehicular trauma, and severity primarily depends on velocity of impact. We describe 33 free-fall injuries in adults occurring under purely nonintentional circumstances at a popular college "spring break" resort. Patterns of injuries were found to differ significantly from previously reported patterns of injuries sustained by adults from both accidental and intentional vertical deceleration. PMID- 8437179 TI - Optimizing prehospital triage criteria for trauma team alerts. AB - Although scores and other prehospital triage schema effectively identify injured patients who will benefit from trauma center care, those tools are relatively nonspecific. One consequence is overtriage--transport of less severely injured patients to trauma centers--with resulting expenditure of scarce resources on patients who do not benefit from an emergent and intensive response. We developed a tool that, during the prehospital phase, can sort inner-city trauma victims into those who will require ICU/OR services and those who will not. Beginning with the trauma triage criteria promulgated by the American College of Surgeons, we created two tiers of personnel response based on vital signs, mechanism of injury, and limited anatomic information ordinarily reported by prehospital providers. Based on our initial experience with the two-tier response, the sorting criteria were revised and refined. The sensitivity of the current version of the two-tier criteria for predicting which trauma patients will require ICU/OR services during the first 24 hours of hospitalization approaches 95% (excluding misapplications of the tool) while avoiding urgent trauma team mobilization in 57% of patients triaged to our trauma center. Two-tiered trauma responses appear to be safe and may represent an important strategy for more effective distribution of increasingly scarce and costly resources. PMID- 8437180 TI - Ordering of laboratory work in the management of pediatric burn patients: technical note. AB - A large number of laboratory tests are often ordered in the management of acutely burned patients. Administration of large volumes of fluid and frequent ventilator changes prompt many facilities to utilize ordering protocols. Forty-five consecutive acutely burned pediatric patients with burns measuring 25% or more of total body surface area (TBSA) sustained within 24 hours before admission were reviewed. Laboratory determinations were made at each shift and as indicated by changes in condition. Abnormal or critical values during the first 5 postinjury days were identified for electrolytes, renal function indices, complete blood counts (CBCs), glucose, and arterial blood gas (ABG) levels. Blood drawn for the laboratory tests was also measured. In the first 5 days postburn a total of 8303 laboratory determinations were made. Of these, 186 produced abnormal values. Four were critical values that were not expected from previous determinations. Of the four unexpected critical values obtained, two would have been picked up by our present standard noninvasive monitors. Six percent of estimated blood volume was used to perform laboratory tests. These results demonstrate that significant abnormal laboratory values are uncommon even in severely injured pediatric burn patients and that the ordering of these tests should be individualized based on patient examination and the use of noninvasive monitoring. PMID- 8437181 TI - Technical note: a quick and simple method of obtaining venous access in traumatic exsanguination. AB - The procedure described here for rapid venous access is simple, involves minimal dissection, and is highly reliable. Difficulty in defining the saphenous vein in the groin is alleviated by the forceful separation of the subcutaneous tissues, which invariably reveals the vein at the base of the wound. The only materials required are a scalpel, surgical ties, and IV tubing. In cases of traumatic exsanguination surgical residents were able to achieve IV access within a minute or less. The disadvantage of this technique is that it requires a long incision. PMID- 8437182 TI - Early evacuation of clotted blood in hemothorax using thoracoscopy: case reports. AB - Hemothorax complicated by clotting of the blood is traditionally treated with thoracotomy. Successful treatment using early thoracoscopy in two patients is described. A third patient, in whom thoracoscopic evacuation failed, is also discussed. Early timing of the procedure appears to enhance the opportunity for adequate drainage of the thorax with lung re-expansion. PMID- 8437183 TI - Delayed presentation of a penetrating suprarenal aortic injury: case report. AB - Death from exsanguination is the immediate outcome in more than 80% of penetrating wounds of the aorta. We report a case in which a gunshot wound to the upper abdomen produced a full-thickness laceration to the diaphragmatic aorta that was missed during the initial exploratory laparotomy. Only 3 days later did the patient develop symptoms of a vascular injury and require reoperation. PMID- 8437184 TI - Commotio cordis in two amateur ice hockey players despite the use of commercial chest protectors: case reports. AB - We describe two recent deaths in 15-year-old male ice hockey players. Both adolescents died of commotio cordis from chest impacts by ice hockey pucks despite their use of commercially designed and manufactured chest protectors. Commotio cordis is discussed as a preventable sports-related injury in the adolescent age group, and the need for improved chest protective equipment in preventing such injuries is also examined. PMID- 8437185 TI - Pulmonary artery perforation after Kirschner wire migration: case report and review of the literature. AB - Utilization of Kirschner wires for bone and joint fixation is potentially complicated by migration of the wire from the fixation site over time. However, a review of the literature disclosed few reports of this complication. We describe such a case in order to emphasize the potential danger of the migration of such metallic devices used near thoracic cavity. PMID- 8437186 TI - Simultaneous bilateral trochanteric and subtrochanteric fractures: case reports. AB - We report three cases of very rare simultaneous bilateral trochanteric and subtrochanteric fractures. These combined fractures are severe, life-threatening injuries that should be treated according to the principles of treatment of multiple injuries. Adequate fluid resuscitation, early one-stage internal fixation of both fractures, and early mobilization of the patient are the major determinants of successful outcome. PMID- 8437188 TI - Ureteral laceration caused by a fall from a height: case report and review of the literature. AB - Ureteral rupture is an uncommon lesion in adults following blunt trauma. We report a case of an adult who sustained a ureteral injury in a fall from a height. To our knowledge this is the first time this has been reported following this mechanism of injury. The diagnosis was made from a CT scan. Prompt surgical repair yielded an excellent result. PMID- 8437187 TI - Heterotopic ossification of the patellar tendon following intramedullary nailing of the tibia: report on two cases. AB - Heterotopic ossification (HO) of the patellar tendon following intramedullary nailing of the tibia for fracture, which has not been previously documented, occurred in 2 of 31 patients reviewed who had adequate follow-up after this procedure. One suffered grade IV HO and the other grade II HO using a modification of the Brooker classification. The patient with grade IV HO had serious disability from pain and decreased range of motion. Risk factors previously suggested were associated with the formation of heterotopic bone in our two patients. These factors included head injury and long-term hypoxemia. PMID- 8437189 TI - In-house trauma surgeon--paradigm or paradox. PMID- 8437190 TI - Surgical approach of choice for penetrating cardiac wounds. AB - One hundred nineteen patients suffered penetrating cardiac trauma over a 15-year period: 59 had gunshot wounds, 49 had stab wounds, and 11 had shotgun wounds. The overall survival rate was 58%. The most commonly injured structures were the ventricles. Twenty-seven patients had injuries to more than one cardiac chamber. Thirty patients had associated pulmonary injuries. Emergency thoracotomy was performed in 47 patients with 15% survival. Median sternotomy was used in 30 patients with 90% survival. Seventeen of the 83 patients with thoracotomies required extension across the sternum for improved cardiac exposure or access to the contralateral hemithorax. Only one patient with sternotomy also required a thoracotomy. All pulmonary injuries were easily managed when sternotomy was used. We conclude that sternotomy provides superior exposure for cardiac repair in patients with penetrating anterior chest trauma. We feel it is the incision of choice in hemodynamically stable patients. Thoracotomy should be reserved for unstable patients requiring aortic cross-clamping, or when posterior mediastinal injury is highly suspected. PMID- 8437191 TI - Magnetic resonance imaging in cervical spine trauma. AB - The ability of magnetic resonance imaging (MRI) to diagnose locked facets was examined in a series of six patients with traumatic cervical spine fractures. Plain films, computed tomography, and magnetic resonance scanning were done immediately following injury. Cord edema, contusions, and acute disc herniation were well visualized on magnetic resonance images. Magnetic resonance proved to be equally effective in diagnosing unilateral and bilateral locked facets, and demonstrated the disruption of the posterior longitudinal ligament (PLL) with clarity. The magnetic resonance diagnostic criteria of locked facets, herniation of intervertebral discs, and rupture of the posterior longitudinal ligament are described. Besides permitting direct visualization of the spinal cord, MRI may have a role in the diagnosis and management of acute bony injury to the cervical spine. PMID- 8437192 TI - Abdominal ultrasound as a reliable indicator for conclusive laparotomy in blunt abdominal trauma. AB - The purpose of this study was to evaluate the ability of abdominal ultrasound (US) to detect intra-abdominal injuries that required surgical repair. We therefore retrospectively reviewed 353 patients with nontrivial blunt abdominal trauma. All patients underwent abdominal evaluation as part of our routine trauma protocol within the first minutes of arrival at our emergency center. Hemoperitoneum and intraperitoneal parenchymal damage were correctly identified by US with a sensitivity of 92.8%, and a specificity of 100%. Accuracy was 99.4%, the positive predictive value was 100%, and the negative predictive value was 99.4% (prior probability of disease was 7.65%). We believe that abdominal US should be considered an important tool and an integral part in the work-up of major trauma victims. PMID- 8437193 TI - Limitations of cervical radiography in the evaluation of acute cervical trauma. AB - We retrospectively reviewed the medical records and cervical films, computed tomographic (CT) scans, and tomographic studies of 216 consecutive patients with cervical injuries. A trauma series of roentgenograms--a cross-table lateral (CTL), a supine anteroposterior, and an open-mouth odontoid view--was performed in 100%; CT scanning was performed in 100%; and tomography was done in 9% of cases. We determined what percentage of the patients were asymptomatic initially in the emergency department; the total numbers of fractures, subluxations, and dislocations of the cervical spine in these patients; and what percentage of the cervical injuries were not detected with the plain films. Of the 216 patients in the series, 188 (87%) had known signs or symptoms of cervical injury; however, 28 (13%) of the patients were initially asymptomatic with no neurologic deficit. Of these 28, 17 were intoxicated or had mild closed head injuries; however, in 11 (5%) there was no clinical clue to their cervical injury other than a known injury mechanism. Prospectively, 67% of the fractures and 45% of the subluxations and dislocations were not detected by the CTL films, and 32% of the patients, over half of whom had unstable cervical injuries, were falsely identified as having normal spines. Prospectively, the trauma series improved the sensitivity of plain films for detecting cervical injuries but still did not detect 61% of the fractures and 36% of the subluxations and dislocations, and falsely identified 23% of the patients, half of whom had unstable cervical injuries, as having normal cervical spines.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437194 TI - Head CT scanning versus urgent exploration in the hypotensive blunt trauma patient. AB - In hypotensive blunt trauma patients with a diminished level of consciousness, it may be difficult to decide whether to proceed with immediate head CT scanning or urgent laparotomy or thoracotomy. The purpose of this study was to determine the frequency of emergency craniotomy and urgent laparotomy or thoracotomy in a group of 734 blunt trauma patients with initial hypotension (BP < 90 mm Hg systolic) admitted to the eight level I and II trauma centers in North Carolina. The mean initial systolic blood pressure was 64 +/- 26 mm Hg, and the mean Trauma Score was 8 +/- 5.8. Serious head injury (AIS head > or = 3) was present in 40% (293 of 734). Of 734 patients studied, 9.4% (69 of 734) died in the emergency department. Head CT scanning was performed on 47% (344 of 734) and produced positive results for 26% (202 of 734). Emergency craniotomy for intracranial hemorrhage was performed on 2.5% (18 of 734) (ten subdurals, three epidurals, and five other intracranial hemorrhages). Twenty-one percent (154 of 734) underwent urgent laparotomy, thoracotomy, or both. Overall hospital mortality for hypotensive blunt trauma patients was 36% (263 of 734). Although serious head injury occurs commonly (40%) in hypotensive blunt trauma patients, frequency of urgent laparotomy (21%) is 8.5 times greater than emergency craniotomy for intracranial hemorrhage (2.5%). This information may be used by trauma teams in prioritizing care for hypotensive blunt trauma patients. PMID- 8437195 TI - Reliability of the Glasgow Coma Scale when used by emergency physicians and paramedics. AB - We sought to determine the reliability of the Glasgow Coma Scale (GCS) when used by emergency physicians and paramedics. We performed a prospective sequential trial in a classroom setting, with subjects blinded to others' scoring. Nineteen university-affiliated emergency physicians and 41 professional paramedics from an urban EMS system voluntarily participated. Participants viewed four videotaped scenes in which a patient is assessed by a paramedic. The first three scenes represented severe, intermediate, and no/mild alteration in level of consciousness (LOC). The findings in the fourth scene were identical to the first, allowing determination of intrarater reliability. The Kappa statistic was used to determine interrater reliability; the reliability coefficient determined intrarater reliability. Kappa was significant (p < 0.0001) for severe (kappa = 0.48), intermediate (kappa = 0.34), and no/mild (kappa = 0.85) conditions. Intrarater reliability (r1,2) for emergency physicians was 0.66 (p < 0.01) and for paramedics was 0.63 (p < 0.01). The GCS shows statistically significant reliability (i.e., significant agreement) between emergency physicians and emergency medical technician-paramedics. It also has a significant level of intrarater reliability. PMID- 8437196 TI - Low-energy subtrochanteric fractures in elderly patients: results of fixation with the sliding screw plate. AB - Forty-two patients with subtrochanteric fractures were treated from 1987 through 1990. Of these, 31 patients above 70 years of age (average, 81.9) had nonpathologic low-energy fractures that were internally fixed with a sliding screw-plate device. Subtrochanteric fractures with an associated intertrochanteric component were the most common type. Interfragmentary compression was used in long oblique and spiral fractures and those with large butterfly fragments. Patients were mobilized early and allowed partial weightbearing for 6-8 weeks. There was a 29% mortality rate within 3 months of injury. Of the remaining cases, followed for a minimum of 6 months (average, 11.8 months), 20 (91%) united satisfactorily. There was loss of fixation in one case and one instance of plate fracture. We found, given the special circumstances in elderly patients, that the device was suitable not only for subtrochanteric fractures with an intertrochanteric element but also for four-part fractures and two-part spiral fractures. The sliding screw-plate permitted passage of interfragmentary screws and facilitated medial displacement and collapse, which are valuable in cases with medial comminution in reducing the bending moment on the plate. These factors may help reduce the incidence of plate failure and, coupled with familiarity with its use, make it a reliable implant for such difficult fractures in elderly patients. PMID- 8437197 TI - Nonunion of tibial shaft fractures treated with locked intramedullary nailing without bone grafting. AB - Twenty-five nonunions of tibial fractures were treated with Grosse-Kempf slotted, locked nails in 20 men and 5 women 6 to 54 months after fracture. No bone grafts were performed in connection with nailing. For better alignment, opening of the nonunion site, fibular osteotomy/resection, or both were used. In one patient reoperation with nailing and bone grafting was necessary after the first nail broke. There were three postoperative infections (12%), two with persistent drainage. All nonunions healed. In one patient an external rotatory malalignment was corrected by a later osteotomy. In no case was the function of the ankle or foot impaired by the index operation. Static locking was not unfavorable for healing. We conclude that bone grafting is rarely needed and function is restored early after locked nailing of tibial nonunions. PMID- 8437198 TI - A new surgical technique for old ununited lateral condyle fractures of the humerus in children. AB - It is difficult to achieve an anatomic reduction of old lateral condyle humeral fractures in spite of extensive excision of fibrous tissues from the condylar fragment. The long-standing displaced position of the condyle is responsible for the contracture of the origin of the common extensor tendon, which prevents anatomic reduction. In our technique, lengthening of the common extensor origin was done and anatomic reduction achieved. This technique has been tried successfully in 15 cases of neglected fractures of lateral humeral condyles in children. PMID- 8437199 TI - Femoral shaft fractures complicated by fracture-dislocations of the ipsilateral hip. AB - A series of 16 consecutive adults with femoral shaft fractures complicated by fracture-dislocations of the ipsilateral hip joint was prospectively studied. There were 11 posterior dislocations and five central dislocations. The treatment consisted of early closed reduction of the dislocation with the assistance of an external fixator, delayed reamed intramedullary nailing of the femoral fracture, and conservative or surgical treatment of the hip joint according to the indications. The follow-up period was 2-8 years (median, 3.5 years). Although an 18.8% (3 of 16) complication rate was noted, the outcome was satisfactory for all 16 hip joints. When such complicated combined injuries are sustained, the technique described here is the most reasonable treatment. PMID- 8437200 TI - Femoral shaft fractures associated with unstable pelvic fractures. AB - From December 1986 to December 1989, 23 consecutive adult patients with femoral shaft fractures associated with unstable pelvic fractures were prospectively studied. The mortality rate was 8.7%. An anterior frame of an external fixator was sometimes inserted emergently in patients with multiple injuries to improve their bedside care. Early reamed femoral intramedullary nailing accompanying closed or open reduction with internal fixation, external fixation or both for unstable pelvic fractures was the favored treatment method. Twenty cases were followed for an average of 26 months. The union rate was high (95%) and the complication rate was low (5%). Hip and knee joint function was also satisfactory. Combined femoral shaft and unstable pelvic fractures are severe injuries and necessitate aggressive emergent management. With the techniques described, patients can achieve optimal outcome. PMID- 8437201 TI - Mucosal tenting suture with stenting in the treatment of chronic laryngotracheal stenosis. AB - A surgical technique of laryngotracheoplasty with long-term stenting was employed exclusively in the treatment of 105 patients with laryngotracheal stenosis in the Department of Otolaryngology, National Taiwan University Hospital from May 1977 to April 1989. The results were satisfactory, 92% of the treated patients being decannulated. The technique of laryngotracheoplasty can be summarized as follows: (1) Exposure of the stenotic region by laryngofissure, anterior and/or posterior cricoid splitting, vertical tracheal incision; (2) debridement of infected soft tissue; (3) relaxation or displacement of heavy scar tissue; (4) placement of sutures to tent the laryngotracheal mucosal remnants to the extraluminal region; (5) insertion of a endolaryngotracheal stent using a silicone T tube; (6) closure of the skin layer of the surgical wound only, without approximating the soft tissue layer between the T tube and skin; and (7) leaving the stent in place for at least 6 months. PMID- 8437202 TI - 'Routine' radiologic evaluation of the thoracolumbar spine in blunt trauma patients: a reappraisal. AB - A retrospective review of 756 blunt trauma cases at a level I trauma center was conducted to determine the role of thoracolumbar (TL) spine roentgenograms in the management of asymptomatic patients. Thoracolumbar spine films were obtained on 106 patients. The charts from 99 patients were available for thorough review. Fifty-five patients had negative clinical evidence of TL spine injury; all of these (100%) had negative radiographic evidence of fracture or dislocation on the TL spine films. Twenty-four patients had positive clinical evidence of TL spine injury; 14 (58%) had corresponding radiographic evidence of TL spine injury. Of the 20 patients in whom the clinical examination was equivocal, one (5%) had radiographic evidence of TL spine injury. We conclude that physical examination is reliable for assessing the TL spine, and that in the absence of clinical evidence of injury, TL spine films are unnecessary. In patients with equivocal examinations, TL spine films should be obtained because 7% (one of 15) of the injuries were identified in this group. PMID- 8437203 TI - Paramilitary punishment in Northern Ireland: a macabre irony. AB - The various types of paramilitary "punishments" occurring during civil disturbances in Northern Ireland are described along with a retrospective analysis of 100 victims of low-velocity punishment gunshot wounds admitted to the Royal Victoria Hospital, Belfast, between July 1, 1986, and December 31, 1989. While "kneecapping" remains the most common form of punishment, an alteration in the character and pattern of injury has resulted in an increase in the incidence of ankle and elbow gunshot wounds. The possibility of a complicated injury involving bone, blood vessel, or nerve (either alone or in combination) occurred in approximately 40% of knee injuries, 70% of ankle injuries, and 30% of elbow injuries. The implications of these alterations in character with respect to provision of hospital care and social morbidity are described. A macabre irony exists in that the punishment policy is dictated by the paramilitary organizations who themselves are the perpetrators of major terrorist crimes. PMID- 8437204 TI - Below knee amputation in war surgery: a review of 111 amputations with delayed primary closure. AB - The results of 111 acute below-knee amputations in war wounded were reviewed. The majority of the patients were wounded by exploding mines. The amputation stumps were not closed primarily but secondarily after an average of 6.4 days. Reamputation above the knee was necessary in only one case of wound sepsis. After delayed primary closure 84% of the stumps healed without problems. The best results were obtained when the stump closure was performed within 1 week after the amputation. No cases of gas gangrene or tetanus were encountered. PMID- 8437205 TI - The futility of predictive scoring of mangled lower extremities. AB - Fifty-eight lower limb salvage attempts over a 10-year period were retrospectively scored using the Mangled Extremity Syndrome Index (MESI), Mangled Extremity Severity Score (MESS), Predictive Salvage Index (PSI), and the Limb Salvage Index (LSI). Primary amputations were excluded. Limb salvage failure was defined at four levels, including functional failure 2 years postinjury. Cross validational sensitivity and specificity analyses revealed no predictive utility in any of the four indices. Although most failed limb salvage attempts could be identified early in the course of management, a significant percentage of our patients suffered prolonged reconstructive efforts. We conclude that efforts must be directed at more precisely determining the factors that aid in the decisions to terminate futile salvage efforts. PMID- 8437206 TI - Correlation of specific virus-astrocyte interactions and cytopathic effects induced by ts1, a neurovirulent mutant of Moloney murine leukemia virus. AB - ts1 is a highly neuropathogenic and lymphocytopathic mutant of Moloney murine leukemia virus TB (MoMuLV-TB). We previously reported that the primary neuropathogenic determinant of ts1 maps to a single amino acid substitution, Val 25-->Ile, in precursor envelope protein gPr80env. This Val-25-->Ile substitution apparently renders gPr80env inefficient for transport from the endoplasmic reticulum to the Golgi apparatus. These findings suggest that the cytopathic effect of ts1 in neural cells might be due to the accumulation of gPr80env in the endoplasmic reticulum. Since endothelial and glial cells are targets of ts1 infection in the central nervous system, we established primary endothelial and astrocyte cultures to investigate the mechanism of cell killing caused by ts1. A continuous cell line, TB, was used as a control. Our results showed that both ts1 and MoMuLV-TB replicated and induced a cytopathic effect in astrocyte cultures, albeit to different degrees; ts1 appeared to be more lethal than MoMuLV-TB. On the other hand, ts1 and MoMuLV-TB infections of endothelial or TB cells were not cytopathic. The cytopathic effect in infected astrocytes correlated with the inefficiency of gPr80env transport and the intracellular accumulation of gPr80env as well as aberrant virus particles. PMID- 8437207 TI - Functional analysis of the herpes simplex virus UL42 protein. AB - The herpes simplex virus UL42 gene encodes a multifunctional polypeptide (UL42) that is essential for virus DNA replication. To further understand the relationship between the structure of UL42 and the role that it plays during virus replication, we analyzed an extensive set of mutant UL42 proteins for the ability to perform the three major biochemical functions ascribed to the protein:binding to DNA, stably associating with the virus DNA polymerase (Pol), and acting to increase the length of DNA chains synthesized by Pol. Selected mutants were also assayed for their ability to complement the replication of a UL42 null virus. The results indicated that the N-terminal 340 amino acids of UL42 were sufficient for all three biochemical activities and could also support virus replication. Progressive C-terminal truncation resulted in the loss of detectable DNA-binding activity before Pol binding, while several mutations near the N terminus of the polypeptide resulted in an altered interaction with DNA but had no apparent affect on Pol binding. More dramatically, an insertion mutation at residue 160 destroyed the ability to bind Pol but had no effect on DNA binding. This altered polypeptide also failed to increase the length of DNA product synthesized by Pol, and the mutant gene could not complement the growth of a UL42 null virus, indicating that the specific interaction between Pol and UL42 is necessary for full Pol function and for virus replication. This study confirms the validity of the Pol-UL42 interaction as a target for the design of novel therapeutic agents. PMID- 8437208 TI - Integration is essential for efficient gene expression of human immunodeficiency virus type 1. AB - A mutant of human immunodeficiency virus type 1 which carries a frameshift insertion in the integrase/endonuclease region of pol gene was constructed in vitro. Upon transfection into cells, although this mutant exhibited a normal phenotype with respect to expression of gag, pol, and env genes and to generation of progeny virions, no replication-competent virus in CD4-positive cells emerged. An assay for the single-step replication of a defective viral genome dependent on trans complementation by rev protein was established and used to monitor the early phase of viral infection process. Viral clones with a mutation in the vif, vpr, or vpu gene displayed no abnormality in the early phase. In contrast, the integrase mutant did not direct a marker gene expression after infection. Together with an observation that the mutant lacked the ability to integrate, these results indicated that the integration was required for efficient viral gene expression and productive infection of human immunodeficiency virus type 1. PMID- 8437210 TI - Fusion formation by the uncleaved spike protein of murine coronavirus JHMV variant cl-2. AB - The fusogenic properties of the uncleaved spike (S) protein of murine coronavirus JHMV variant cl-2 were studied by expressing the S protein with a deleted putative cleavage site. The amino acid sequence of the putative cleavage site, Arg-Arg-Ala-Arg-Arg, was replaced by Arg-Thr-Ala-Leu-Glu by in vitro mutagenesis of the cl-2 S protein cDNA. Recombinant vaccinia viruses containing the cl-2 S cDNA [RVV t(+)] or the mutated cDNA [RVV t(-)] were constructed and monitored for fusion formation and cleavage of the expressed S proteins. When cultured DBT cells were infected with RVV t(+) at a multiplicity of infection of 0.5, fusion formation was first observed at 10 to 12 h postinoculation and spread throughout the whole culture by 20 to 24 h postinoculation. In cells infected with RVV t(-) under the same conditions, fusion formation appeared by 12 to 14 h. This result represented a 2- to 4-h delay in the onset of fusion, compared with its appearance in cells expressing the wild-type S protein. By 25 to 30 h, most of the cells infected by RVV t(-) had fused. By immunoprecipitation and Western blotting (immunoblotting), the 170-kDa S protein was detected in DBT cells expressing the wild-type S protein and the mutated S protein. However, interestingly, the cleavage products of the S protein, S1 and S2, were not detected in RVV t(-)-infected cells, producing the mutated S protein, even though fusion was clearly visible. Both products were, of course, detected in RVV t(+) infected DBT cells, producing the wild-type S protein. The same results concerning the fusion formation and cleavage properties of the S proteins were reproduced by the transiently expressed S proteins. These results suggest that the cleavage event in the S protein of murine coronavirus JHMV is not a prerequisite for fusion formation but that it does facilitate fusion formation. PMID- 8437209 TI - Genetic heterogeneity in human T-cell leukemia/lymphoma virus type II. AB - DNA from the peripheral blood mononuclear cells of 17 different individuals infected with human T-cell lymphoma/leukemia virus type II (HTLV-II) was successfully amplified by the polymerase chain reaction (PCR) with the primer pair SK110/SK111. This primer pair is conserved among the pol genes of all primate T-cell lymphoma viruses (PTLV) and flanks a 140-bp fragment of DNA which, when used in comparative analyses, reflects the relative degree of diversity among PTLV genomes. Cloning, sequencing, and phylogenetic comparisons of these amplified 140-bp pol fragments indicated that there are at least two distinct genetic substrains of HTLV-II in the Western Hemisphere. These data were confirmed for selected isolates by performing PCR, cloning, and sequencing with to 10 additional primer pair-probe sets specific for different regions throughout the PTLV genome. HTLV-II isolates from Seminole, Guaymi, and Tobas Indians belong in the new substrain of HTLV-II, while the prototype MoT isolate defines the original substrain. There was greater diversity among HTLV-II New World strains than among HTLV-I New World strains. In fact, the heterogeneity among HTLV-II strains from the Western Hemisphere was similar to that observed in HTLV-I and simian T-cell lymphoma/leukemia virus type I isolates from around the world, including Japan, Africa, and Papua New Guinea. Given these geographic and anthropological considerations and assuming similar mutation rates and selective forces among the PTLV, these data suggest either that HTLV-II has existed for a long time in the indigenous Amerindian population or that HTLV-II isolates introduced into the New World were more heterogeneous than the HTLV-I strains introduced into the New World. PMID- 8437211 TI - Marburg virus gene 4 encodes the virion membrane protein, a type I transmembrane glycoprotein. AB - Gene 4 of Marburg virus, strain Musoke, was subjected to nucleotide sequence analysis. It is 2,844 nucleotides long and extends from genome position 5821 to position 8665 (EMBL Data Library, emnew: MVREPCYC [accession no. Z12132]). The gene is flanked by transcriptional signal sequences (start signal, 3' UACUUCUUGUAAUU-5'; termination signal, 3'-UAAUUCUUUUU-5') which are conserved in all Marburg virus genes. The major open reading frame encodes a polypeptide of 681 amino acids (M(r), 74,797). After in vitro transcription and translation, as well as expression in Escherichia coli, this protein was identified by its immunoreactivity with specific antisera as the unglycosylated form of the viral membrane glycoprotein (GP). The GP is characterized by the following four different domains: (i) a hydrophobic signal peptide at the amino terminus (1 to 18), (ii) a predominantly hydrophilic external domain (19 to 643), (iii) a hydrophobic transmembrane anchor (644 to 673), and (iv) a small hydrophilic cytoplasmic tail at the carboxy terminus (674 to 681). Amino acid analysis indicated that the signal peptide is removed from the mature GP. The GP therefore has the structural features of a type I transmembrane glycoprotein. The external domain of the protein has 19 N-glycosylation sites and several clusters of hydroxyamino acids and proline residues that are likely to be the attachment sites for about 30 O-glycosidic carbohydrate chains. The region extending from positions 585 to 610 shows significant homology to a domain observed in the envelope proteins of several retroviruses and Ebola virus that has been suspected to be responsible for immunosuppressive properties of these viruses. A second open reading frame of gene 4 has the coding capacity for an unidentified polypeptide 112 amino acids long. PMID- 8437212 TI - Proliferative response of Tax1-transduced primary human T cells to anti-CD3 antibody stimulation by an interleukin-2-independent pathway. AB - The growth properties of human T-cell leukemia virus Tax1-transduced primary human T cells derived from peripheral blood lymphocytes were compared with those of the same subset of T cells transduced with a control vector. Tax1-transduced T cells exhibited slightly elevated responsiveness to externally added interleukin 2 (IL-2) and a markedly higher proliferative response to stimulation with anti CD3 antibody. The proliferation after anti-CD3 antibody stimulation was mainly via an IL-2-independent pathway. Therefore, some other mechanism than the previously proposed IL-2 autocrine model seems to be involved in the process of deregulation of T-cell proliferation by Tax1. Moreover, Tax1-transduced T cells have continued to proliferate in medium containing IL-2 long after control T cells ceased to grow, and so they are considered to be immortalized. PMID- 8437213 TI - The woodchuck hepatitis virus X gene is important for establishment of virus infection in woodchucks. AB - All mammalian hepadnaviruses possess a gene, termed X, that encodes a protein capable of transactivating virus gene expression. The X gene overlaps the polymerase and precore genes as well as two newly identified open reading frames (ORFs) termed ORF5 and ORF6. In this investigation, we examined whether ORF5, ORF6, and the X gene were important for the replication of woodchuck hepatitis virus (WHV) in susceptible woodchucks. First, we investigated whether proteins were produced from ORF5 and ORF6 by in vitro translation of appropriate viral transcripts, searched for antibodies against the putative proteins in the sera of animals infected with wild-type virus, and looked for an antisense WHV transcript, necessary for expression of a protein from ORF6, in the livers of acutely or chronically infected woodchucks. All such experiments yielded negative results. Next, we used oligonucleotide-directed mutagenesis to introduce termination codons into ORF5 and ORF6 at two locations within each ORF. Adult woodchucks in groups of three were transfected with one of the four mutant genomes. All of these woodchucks developed WHV infections that were indistinguishable from those of animals transfected with the wild-type WHV recombinant. Polymerase chain reaction amplification and direct DNA sequencing confirmed that reversion of the mutants to a wild-type genotype did not occur. Taken together, these data indicate that ORF5 and ORF6 are not essential for virus replication and are unlikely to represent authentic genes. Finally, we generated five WHV X-gene mutants that either removed the initiation codon for protein synthesis or truncated the carboxyl terminus of the protein by 3, 16, 31, or 52 amino acids. Groups of three adult woodchucks were transfected with one of the five X-gene mutants. Only the mutant that possessed an X gene lacking 3 amino acids from the carboxyl terminus was capable of replication within the 6-month time frame of the experiment. In contrast, all seven woodchucks transfected with wild-type WHV DNA developed markers consistent with viral infection. Thus, it is likely (P < 0.01) that the WHV X gene is important for virus replication in the natural host. PMID- 8437215 TI - Immunological responses of mice and cattle to baculovirus-expressed F and H proteins of rinderpest virus: lack of protection in the presence of neutralizing antibody. AB - Rinderpest is a highly contagious viral disease of ruminants and has greater than 95% morbidity and mortality. The etiological agent, rinderpest virus (RPV), is a member of the family Paramyxoviridae and the genus Morbillivirus. Immune responses to both the hemagglutinin (H) and the fusion (F) antigens of morbilliviruses play an important role in the prevention of infection, and only attenuated live vaccines have been shown to provide protective immunity against the group. The lack of protection with inactivated vaccines has been attributed to the denaturation of the F glycoprotein of the virus. Our previous study, however, demonstrated complete protection of cattle vaccinated with infectious vaccinia virus recombinants expressing the H (vRVH) or F (vRVF) protein alone, even in the presence of only 4 U of serum-neutralizing (SN) antibody to RPV (T. Yilma, D. Hsu, L. Jones, S. Owens, M. Grubman, C. Mebus, M. Yamanaka, and B. Dale, Science 242:1058-1061, 1988). We have constructed recombinant baculoviruses that express the F (Fb) and H (Hb) glycoproteins of RPV. Furthermore, we have analyzed the immune responses of mice and cattle to these antigens. Cattle vaccinated with Fb or Hb or a mixture of both antigens were not protected from challenge inoculation with RPV, even when the SN titer was greater than in cattle vaccinated with vRVF alone. This lack of protection, in the presence of SN antibody, would indicate that live attenuated and recombinant vaccines induce immune responses necessary for protection (e.g., cell-mediated immunity) that are not generated by subunit or inactivated whole-virus vaccines. PMID- 8437216 TI - Structure of a Moloney murine leukemia virus-virus-like 30 recombinant: implications for transduction of the c-Ha-ras proto-oncogene. AB - Tumor progression locus 2 (Tpl-2) encodes a novel serine-threonine protein kinase which is activated by provirus integration in the late stages of oncogenesis in Moloney leukemia virus (MoMuLV) induced rat T-cell lymphomas. In this report, we present evidence that the provirus integrated in the Tpl-2 locus in 1 of 10 T cell lymphomas harboring a Tpl-2 rearrangement (2779) is a recombinant between MoMuLV and virus-like 30 (VL30) sequences (Mo-VL30). Recombination between MoMuLV and VL30 may contribute to the transduction of ras, as suggested by the finding that VL30 flanks the ras oncogene in all of the ras transducing viruses isolated from rats to date. The Mo-VL30 recombinant described here represents evidence that recombination between MoMuLV and VL30 can be uncoupled from the transduction of ras, and it may precede the transduction. Sequence comparison between clones of Mo-VL30, Harvey sarcoma virus (Ha-MSV), and genomic c-Ha-ras revealed that all three share a 124-bp region of 87.3% homology. This region was detected at nucleotide positions -1845 to -1720 of c-Ha-ras and 20 bp 5' of the recombination breakpoint between VL30 and ras in Ha-MSV. On the basis of the sequence comparison between VL30, Ha-MSV, and c-Ha-ras, we are proposing a model which explains how VL30 may have facilitated the transduction of c-Ha-ras and perhaps the other ras proto-oncogenes. According to this model, the sequence homology between VL30 and c-Ha-ras targets this gene for transduction by promoting the integration of the provirus in this locus through homologous recombination. PMID- 8437214 TI - Simian immunodeficiency viruses from central and western Africa: evidence for a new species-specific lentivirus in tantalus monkeys. AB - Although up to 50% of African green monkeys (AGMs) are infected by simian immunodeficiency viruses (SIV) in their natural habitat, they remain asymptomatic carriers of these lentiviruses. They provide an attractive model to study not only the origin but also the link among genetic variation, host-virus adaptation, and pathogenicity of primate lentiviruses. SIVagm have been isolated from three species of AGM: the vervet (Cercopithecus pygerythrus), the grivet (Cercopithecus aethiops), and the sabaeus (Cercopithecus sabaeus) monkey. We studied four new SIVagm isolates from a fourth AGM species, the tantalus monkey (Cercopithecus tantalus), caught in the Central African Republic, and four new isolates from feral sabaeus monkeys from Senegal. Antigenic properties and partial env sequences were used to evaluate the diversity among these isolates. Alignment of env sequences in SIVagm isolated from tantalus and sabaeus monkeys permitted detailed mapping of the variable and conserved domains in the external glycoprotein. Genetic distances indicated that SIVagm isolates from tantalus monkeys are the most divergent among SIVagm in feral AGMs in Africa. The fact that AGMs are infected by four distinct lentiviruses, each specific for a single AGM species, supports the hypothesis of a coevolution of these viruses and their natural hosts and suggests that SIV transmission is a rare event among separated AGM species in the wild. PMID- 8437217 TI - Relevance of cysteine residues for biosynthesis and antigenicity of human hepatitis B virus e protein. AB - The mature form of the secretory core protein (HBe protein) of human hepatitis B virus contains four cysteines which are located at amino acid positions -7, 48, 61, and 107 relative to the HBc start methionine. In addition, there is a cysteine, Cys-183, located in the C-terminal domain of the HBe precursor, which is cleaved during HBe maturation. Here, the significance of these cysteines for biosynthesis and antigenicity of the HBe protein was examined. The cysteines at positions -7 and 61 were found to be crucial for HBe biosynthesis. As has already been described, if the Cys at position -7 is mutated, disulfide-linked HBe homodimers which have both HBe antigenicity and HBc antigenicity are expressed. Here we show that these dimers are due to Cys-61-Cys-61 disulfide bridges which are formed only if the Cys at position -7 is not present. In the wild-type protein, this dimerization appears to be inhibited by formation of intramolecular disulfide bridges between the Cys at -7 and one of the internal cysteines. Moreover, Cys-61 is important for HBe biosynthesis in general since mutation of this amino acid results in production of HBe proteins which are either only poorly secreted or possess a different antigenicity. PMID- 8437218 TI - Erythropoietin receptor (EpoR)-dependent mitogenicity of spleen focus-forming virus correlates with viral pathogenicity and processing of env protein but not with formation of gp52-EpoR complexes in the endoplasmic reticulum. AB - Recent evidence suggests that interactions between spleen focus-forming virus (SFFV) env products and the erythropoietin receptor (EpoR) are responsible for viral pathogenicity. Infection of factor-dependent cell lines expressing epoR (the cloned gene for EpoR) with SFFVP is mitogenic, generating cell lines that are no longer dependent on added growth factor, and an immunoprecipitable complex between EpoR and immature env protein in the endoplasmic reticulum has been identified. The dependence of these in vitro activities on env protein processing and their relationship to pathogenicity of SFFV were explored by using glycosylation site mutants of SFFV env. Mutants carrying Asn-->Asp mutations at each of the two consensus signals for N-linked glycosylation in the N-terminal domain of SFFVAP-L env (gs1 and gs2), the gs1-2- double mutant, and the gs0 quadruple mutant (mutated at all four signals utilized for N-linked glycosylation in SFFVAP-L env) were made. The primary translation products (gp52) of single site mutant envs were processed into more highly glycosylated forms, and the corresponding viruses induced splenomegaly in susceptible mice, whereas the gs1-2 and gs0 proteins were not processed, and these viruses were not pathogenic. Unprocessed env proteins of both pathogenic and nonpathogenic mutants coprecipitated with EpoR. In the BaF3 cell assay for epoR-dependent mitogenicity, the pathogenic single mutants induced factor-independent growth efficiently whereas the nonpathogenic gs1-2- and gs0 mutants did not. These data demonstrate that the ability of gp52 to form complexes with EpoR in the endoplasmic reticulum is not sufficient for either mitogenicity in cell culture or induction of splenomegaly in mice while supporting the hypothesis that pathogenicity and mitogenicity of SFFV both result from an interaction between EpoR and SFFV env protein. PMID- 8437219 TI - Polydnavirus genome segment families in the ichneumonid parasitoid Hyposoter fugitivus. AB - Sequences homologous to encapsidated polydnavirus genome segments are routinely detected in parasitoid chromosomal DNA; typically, each viral genome segment hybridizes to a single cognate chromosomal locus. In the present study, we show that in some cases, two or more viral genome segments may hybridize to the same chromosomal locus. Genome segments of this type invariably share a majority of restriction enzyme sites, a fact suggesting derivation from a common template. Families of viral genome segments appear to be relatively common in the Hyposoter fugitivus polydnavirus genome. PMID- 8437220 TI - A subset of Pr65gag is nucleus associated in murine leukemia virus-infected cells. AB - Nuclei of cells infected with Moloney murine leukemia virus (MoMuLV) were examined for the presence of gag proteins. This analysis was performed in conjunction with other studies suggesting a possible role for gag proteins in regulating nuclear events relating to processing and/or transport of viral genomic RNA. We detected Pr65gag and a p30-related protein in a nuclear fraction of infected cells. We also found evidence that a highly conserved amino acid sequence, which is shared by p30 and U1 small nuclear ribonucleoprotein 70-kDa protein, is a component of the nuclear targeting sequence for Pr65gag. Immunoelectron microscopy studies with a monoclonal anti-p12 antibody established that approximately 18% of gag-containing proteins of MoMuLV are located in the nucleus. Such gag-containing proteins from a mutant MoMuLV that lacks N-terminal myristic acid had greater affinity for the nucleus, suggesting that fatty acid acylation of Pr65gag plays a role in overcoming the proposed nuclear transport signal. The possible roles that nuclear gag proteins may play in retroviral replication are discussed. PMID- 8437221 TI - Low-pH conformational changes of rabies virus glycoprotein and their role in membrane fusion. AB - Fusion of rabies virus with membranes occurs at acidic pH and is mediated by the viral spike glycoprotein (G). In this paper, we provide the basis for a description of structural transitions associated with exposure to low pH and of their role in membrane fusion. First, we have extended previous studies of fusion kinetics and we have shown that low-pH inhibition of fusion is detectable at 0.5 pH units higher than fusion. Second, low-pH-induced conformational changes were analyzed by using electron microscopy and monoclonal antibody binding assays. The existence of a pH-dependent equilibrium between the native and a low-pH inactive conformation was demonstrated. Third, besides these two conformations, we, using the fluorescent probe ANS (8-anilino-1-naphthalenesulfonic acid), provide evidence for the existence of a transient third state which appears to be more hydrophobic than the native state. Our results suggest that this transient state is responsible for viral aggregation at low pH and could play a role in the first steps of the fusion mechanism. PMID- 8437222 TI - Characterization of Bunyamwera virus S RNA that is transcribed and replicated by the L protein expressed from recombinant vaccinia virus. AB - Analysis of the 5' termini of Bunyamwera virus S segment mRNAs by cloning and sequence analysis revealed the presence of nonviral, heterogeneous sequences 12 to 17 bases long. This is similar to reports for other members of the family Bunyaviridae and is taken to indicate that mRNA transcription is primed by a "cap snatching" mechanism. The 3' end of the Bunyamwera virus S mRNA was mapped, by using an RNase protection assay, to 100 to 110 nucleotides upstream of the 3' end of the template. Previously we reported expression of the Bunyamwera virus L (polymerase) protein by recombinant vaccinia virus and demonstrated that the recombinant L protein was functional in terms of RNA synthesis activity in a nucleocapsid transfection assay (H. Jin and R. M. Elliott, J. Virol. 65: 4182 4189, 1991). In the present study we further analyze the RNAs made by using this system and show that positive-sense RNAs contain 5' nonviral sequences. Hence the initiation of mRNA transcription by the recombinant L protein resembles that seen during authentic bunyavirus infection and suggests that the L protein has the endonuclease activity which generates the primers. Some of these positive-sense transcripts terminated at the mRNA termination site, but the majority read through to the end of the template. No primer sequences were found at the 5' terminal of negative-sense RNAs. The recombinant L protein was able to replicate negative-sense RNA supplied by transfected virion-derived nucleocapsids, and both positive- and negative-sense RNAs were synthesized. These results indicate that the recombinant L protein has both transcriptase and replicase activities. PMID- 8437223 TI - Characterization of a glial cell line persistently infected with borna disease virus (BDV): influence of neurotrophic factors on BDV protein and RNA expression. AB - Borna disease virus (BDV) infects cells of the nervous system in a wide range of species. Previous work suggests that there are differences in BDV replication in neuronal cells and glial cells. Many neurons are lysed by the immunopathologic response to BDV; lysis of dentate gyrus neurons in the absence of encephalitis is seen in rats inoculated with BDV as neonates. In contrast, persistently BDV infected astrocytes increase over the course of BDV infection. Therefore, we compared BDV replication in neuronal (SK-N-SH and SK-N-SHEP) and astrocytic (C6) cell lines. While SK-N-SH cells produced more infectious virions per cell, the C6 cells contained more BDV proteins and RNA. BDV sequences in the supernatants of both cell types were identified, despite low titers of infectious virus, suggesting the release of incomplete virions into the medium. C6 cells secreted a factor or factors into the medium that enhanced the production of BDV proteins and RNA in other cell lines. In addition, nerve growth factor treatment produced the same enhancement. Thus, BDV replication in certain neural cells in vitro may be linked to the production of cell-specific factors which affect viral replication. PMID- 8437224 TI - Two mechanisms of soluble CD4 (sCD4)-mediated inhibition of human immunodeficiency virus type 1 (HIV-1) infectivity and their relation to primary HIV-1 isolates with reduced sensitivity to sCD4. AB - Two assays for measuring inhibition of human immunodeficiency virus type 1 (HIV 1) infection by soluble CD4 (sCD4) are described. Experiments in which sCD4, HIV 1, and cell concentrations and sequence of combination, noninfectious/infectious particle ratio, and temperature were varied produced results that support the conclusion that sCD4 inhibits HIV-1 infection by two mechanisms: reversible blockage of receptor binding and irreversible inactivation of infectivity. Fresh isolates obtained from HIV-1-infected persons were tested in both assays and found to be more resistant to both mechanisms of sCD4-mediated inhibition than multiply passaged laboratory strains. Binding studies revealed similar affinities for sCD4 in detergent lysates of sensitive and resistant strains at both 4 and 37 degrees C. The avidity of intact virions for sCD4 was lower at 4 than at 37 degrees C, and in the presence of excess sCD4, less sCD4 was bound at 4 than at 37 degrees C. The avidity differences were similar for fresh isolates and laboratory strains. However, fresh isolates were more resistant to sCD4-induced shedding of envelope glycoprotein gp120 from intact virions than was the laboratory strain. Relative resistance to sCD4 by certain isolates does not represent a lower intrinsic affinity of their envelope for sCD4 or a lower capacity for sCD4 binding. Rather, an event that occurs after binding may account for the differences. This postbinding event or feature may be determined by regions of the envelope outside the CD4 binding site. PMID- 8437225 TI - Characterization of functional Sp1 transcription factor binding sites in the hepatitis B virus nucleocapsid promoter. AB - The hepatitis B virus nucleocapsid minimal promoter contains sequence elements which are similar to the Sp1 transcription factor binding site consensus sequence. The interaction of these regulatory elements with Sp1 was examined by DNase I footprinting with purified Sp1 protein and DNase I footprinting and gel retardation analysis with nuclear extracts from human cell lines and was examined functionally with transient transfection assays in human hepatoma and Drosophila melanogaster Schneider line-2 cells. DNase I footprinting identified two regions of the nucleocapsid promoter, representing three recognition elements, that bound purified Sp1. Gel retardation analysis with Huh7 nuclear extracts demonstrated that each of the three recognition elements bound the same or similar transcription factor(s) as that recognized by the Sp1 consensus sequence recognition element. The function of the nucleocapsid promoter elements was examined by transient transfection assays in D. melanogaster Schneider line-2 cells by using these binding sites cloned into a minimal promoter element. Each of these regulatory regions transactivated transcription from the minimal promoter element in response to exogenously expressed Sp1. In addition, the second Sp1 site was shown to be an essential element of the nucleocapsid promoter in human hepatoma cells. This demonstrates that the hepatitis B virus nucleocapsid promoter contains three functional Sp1 binding sites which may contribute to the level of transcription from this promoter during viral infection. PMID- 8437226 TI - Cell fusion by the envelope glycoproteins of persistent measles viruses which caused lethal human brain disease. AB - Measles virus (MV) rarely induces lethal diseases of the human central nervous system characterized by reduced expression of the viral envelope proteins and by lack of viral budding. The MV envelope contains two integral membrane proteins, termed fusion (F) protein and hemagglutinin (H) protein, and a membrane associated matrix (M) protein. Previously, analysis of MV genes from autopsy material indicated that the M protein and the F protein intracellular domain are often drastically altered by mutations. Here, we present evidence that truncation of the F protein intracellular domain does not impair fusion function, and we suggest that this alteration interferes with viral budding. Unexpectedly, certain combinations of functional F and H proteins were unable to induce syncytium formation, an observation suggesting that specific F-H protein interactions are required for cell fusion. We also found that three of four H proteins of persistent MVs are defective in intracellular transport, oligosaccharide modification, dimerization, and fusion helper function. Thus, MVs replicating in the brain at the terminal stage of infection are typically defective in M protein and in the two integral membrane proteins. Whereas the M protein appears dispensable altogether, partial preservation of F-protein function and H-protein function seems to be required, presumably to allow local cell fusion. Certain subtle alterations of the F and H proteins may be instrumental for disease development. PMID- 8437227 TI - Bovine respiratory syncytial virus protects cotton rats against human respiratory syncytial virus infection. AB - Human respiratory syncytial virus (HRSV) is the most frequent cause of severe respiratory infections in infancy. No vaccine against this virus has yet been protective, and antiviral drugs have been of limited utility. Using the cotton rat model of HRSV infection, we examined bovine respiratory syncytial virus (BRSV), a cause of acute respiratory disease in young cattle, as a possible vaccine candidate to protect children against HRSV infection. Cotton rats were primed intranasally with graded doses of BRSV/375 or HRSV/Long or were left unprimed. Three weeks later, they were challenged intranasally with either BRSV/375, HRSV/Long (subgroup A), or HRSV/18537 (subgroup B). At intervals postchallenge, animals were sacrificed for virus titration and histologic evaluation. Serum neutralizing antibody titers were determined at the time of viral challenge. BRSV/375 replicated to low titers in nasal tissues and lungs. Priming with 10(5) PFU of BRSV/375 effected a 500- to 1,000-fold reduction in peak nasal HRSV titer and a greater than 1,000-fold reduction in peak pulmonary HRSV titer upon challenge with HRSV/Long or HRSV/18537. In contrast to priming with HRSV, priming with BRSV did not induce substantial levels of neutralizing antibody against HRSV and was associated with a delayed onset of clearance of HRSV upon challenge. Priming with BRSV/375 caused mild nasal and pulmonary pathology and did not cause exacerbation of disease upon challenge with HRSV/Long. Our findings suggest that BRSV may be a potential vaccine against HRSV and a useful tool for studying the mechanisms of immunity to HRSV. PMID- 8437228 TI - The negative effect of human immunodeficiency virus type 1 Nef on cell surface CD4 expression is not species specific and requires the cytoplasmic domain of CD4. AB - The nef gene product of human immunodeficiency virus type 1 has been shown to induce CD4 downregulation from the surface of human cells. To determine if this effect is species specific, we used a retroviral vector to transduce the human immunodeficiency virus type 1 nef gene into murine cells expressing human, chimpanzee, or murine CD4. Our results indicate that Nef induces cell surface downregulation of all three molecules. We also determined that Nef is functional in murine T cells and induces downregulation of both murine CD4 and CD8 (Ly-2) from the cell surface. In contrast, Nef does not downregulate cell surface expression of human CD8 in either murine or human cells. By using a mutant of human CD4 lacking its cytoplasmic domain and a human CD4/CD8 chimera, we determined that the cytoplasmic domain of CD4 is required for its downregulation by Nef. Transduction with a control vector had no effect on CD4 cell surface levels, indicating that retroviral transduction by itself has no significant effect on the cell surface levels of CD4. These results show that the observed downregulation of CD4 by Nef is independent of human-specific factors, is not species specific, and requires the cytoplasmic domain of CD4. PMID- 8437229 TI - Vaccinia virus-specific CD8+ cytotoxic T lymphocytes in humans. AB - Stimulation of human vaccinia virus immune peripheral blood mononuclear cells in vitro from vaccinia virus-immune donors with live vaccinia virus-infected autologous cells generated vaccinia virus-specific cytotoxic T lymphocytes (CTL) capable of lysing vaccinia virus-infected cells. We generated vaccinia virus specific CD8+ clones and CD4+ CTL lines by limiting dilution from two donors by using peripheral blood mononuclear cells obtained 2 months or 4 years postrevaccination with vaccinia virus. These results demonstrate that vaccinia virus-specific CTL are generated as a result of immunization of humans with vaccinia virus and that both CD8(+)- and CD4(+)-specific T cells are maintained as memory cells. PMID- 8437230 TI - Asymmetric resolution of a parvovirus palindrome in vitro. AB - Cell extracts from murine A9 or human HeLa cells containing wild-type copies the NS1 polypeptide of minute virus of mice (MVM), produced from a recombinant vaccinia virus, can support the resolution of viral 3' termini from palindromic junction fragments of dimeric, replicative-form MVM DNA. Resolution resulted in the generation of two new viral termini, one associated with each arm of the junction palindrome. Telomeres were created in two configurations, "extended" forms, which were covalently associated with NS1 molecules, and smaller "turn around" forms in which a single arm of the palindrome terminated at the axis of dyad symmetry in a covalent bond which cross-linked the two strands. The in vitro resolution reaction was asymmetric, generating predominantly extended-form termini from one arm of the palindrome but predominantly turn-around forms from the other. This asymmetry was independent of the type of cell used to prepare the in vitro extract or the orientation of the palindrome in the plasmid and was obtained for all cloned junction sequences of 156 bp or more. Two modified forms of the duplex junction fragment, which appeared to be intermediates in the resolution process since they were nicked, covalently linked to NS1, and associated with newly synthesized DNA, were identified. The structures of these intermediates suggest that resolution is initiated by preferential nicking at one of the two candidate resolution sites. The asymmetric nature of this resolution reaction is discussed in terms of current models of MVM DNA replication. PMID- 8437231 TI - The E1B 19-kilodalton protein is not essential for transformation of rodent cells in vitro by adenovirus type 5. AB - The newly constructed adenovirus type 5 mutant in1 carries a single AT base pair insertion immediately after nucleotide position 1715 in the E1B gene sequence which destroys the proximal AUG normally present in E1B messages and prevents production of intact E1B 19-kDa protein in infected cells. We have used in1, variants of in1 containing mutant alleles of viral genes known to enhance transformation frequency, and adenovirus type 5 mutant dl337 (S. Pilder, J. Logan, and T. Shenk, J. Virol. 52:664-671, 1984), in which the sequence between nucleotides 1770 and 1916 within the 19-kDa reading frame is deleted, to test the generally accepted hypothesis that this E1B protein is essential for the transformation of rodent cells and maintenance of the transformed phenotype. We find that these mutants transform rat embryo cells, rat kidney and mouse kidney primary cells, and cells of the 3Y1 rat line with decreased frequencies only when virus is added to these various cells at high input multiplicities of infection. In contrast, when lower doses of virus are used, the mutants transform with wild type frequencies. Cells infected with higher doses of mutant virus show increased levels of DNA degradation and cell killing compared with those of cells infected with the same levels of wild-type virus, and these effects most likely contribute to the decreased transformation frequencies observed. On the basis of these results and the results of phenotypic analyses of numerous transformants, we propose that the E1B 19-kDa protein is not required for induction and/or maintenance of transformed-cell characteristics in rodent cells infected with adenovirus type 5. PMID- 8437232 TI - Autologous antibody response against the principal neutralizing domain of human immunodeficiency virus type 1 isolated from infected humans. AB - High titers of neutralizing antibodies in human immunodeficiency virus type 1 (HIV-1) infection are directed primarily against the third hypervariable domain (V3) of the virion envelope glycoprotein gp120. This region has been designated the principal neutralizing domain of HIV-1. Because the frequency and significance of autologous V3 antibodies in natural infection are not fully clarified, we have cloned, sequenced, and expressed the V3 domain from virus of HIV-1-infected patients to test the autologous and heterologous V3 antibody response. The resulting recombinant Escherichia coli V3 fusion proteins reacted strongly with both autologous and heterologous patient antibodies in Western blots. Thirty-one different V3 fragments were cloned from 24 hemophiliac patients with different immunological and clinical statuses. Antibody reactivity against the autologous V3 fusion proteins was detected in all serum samples except one; moreover, all serum samples contained antibody reactivity against a vast majority of heterologous fusion proteins despite significant amino acid variability in V3. The results suggest that V3 antibodies are highly prevalent; further, we find no association between the stage of the HIV-1 infection and the presence of V3 antibodies. PMID- 8437233 TI - Deletion analysis of the capsid protein of Sindbis virus: identification of the RNA binding region. AB - The capsid protein of Sindbis virus has multiple functions in the life cycle of the virus. One essential function is to interact with the genomic RNA of the virus to form the nucleocapsid. The experiments described in this article define a region of the protein that is required for binding to Sindbis virus RNA. The assay we used measured the binding of in vitro-translated proteins to RNA on the basis of their migration with the RNA during electrophoresis in an agarose gel. Binding to RNA showed specificity; more protein bound to an RNA containing the previously defined packaging signal in Sindbis virus RNAs than to a similar RNA lacking this sequence. We were able to produce a variety of deleted forms of the capsid protein by constructing cDNAs with in-frame deletions throughout the coding region of the capsid protein gene. These cDNAs were then transcribed into mRNAs and translated in vitro. C-terminal deletions in the capsid protein were obtained by preparing transcripts from cDNAs linearized at sites within the coding region. Our studies identified a 32-amino-acid region that is essential for the specificity in RNA binding, and they defined a 68-amino-acid minimal sequence which displays almost the complete specific RNA binding activity of the intact Sindbis virus capsid protein containing 264 amino acids. PMID- 8437234 TI - Calcium ions are required for cell fusion mediated by the CD4-human immunodeficiency virus type 1 envelope glycoprotein interaction. AB - Calcium ions are required for fusion of a wide variety of artificial and biological membranes. To examine the role of calcium ions for cell fusion mediated by interactions between CD4 and the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (gp120-gp41), we used two experimental systems: (i) cells expressing gp120-gp41 and its receptor CD4, both encoded by recombinant vaccinia viruses, and (ii) chronically infected cells producing low levels of HIV 1. Fusion was measured by counting the number of syncytia and by monitoring the redistribution of fluorescence dyes by video microscopy. Syncytia did not form in solutions without calcium ions. Addition of calcium ions partially restored the formation of syncytia. EDTA and EGTA [ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid] blocked syncytium formation in culture media containing calcium ions. Membrane fusion as monitored by fluorescence dye redistribution also required calcium ions. Cell fusion increased with an increase in calcium ion concentration from 100 microM to 10 mM but was not affected by magnesium ions in the concentration range from 0 to 30 mM. Fibrinogen and fibronectin did not promote fusion in the absence or presence of Ca2+. Binding of soluble CD4 to gp120-gp41-expressing cells was not affected by Ca2+ and Mg2+. We conclude that Ca2+ is involved in postbinding steps in cell fusion mediated by the CD4-HIV-1 envelope glycoprotein interaction. PMID- 8437235 TI - Replication of type 1 human immunodeficiency viruses containing linker substitution mutations in the -201 to -130 region of the long terminal repeat. AB - In previous transfection analyses using the chloramphenicol acetyltransferase reporter gene system, we determined that linker substitution (LS) mutations between -201 and -130 (relative to the transcription start site) of the human immunodeficiency virus type 1 long terminal repeat (LTR) caused moderate decreases in LTR transcriptional activity in a T-cell line (S. L. Zeichner, J. Y. H. Kim, and J. C. Alwine, J. Virol. 65:2436-2444, 1991). In order to confirm the significance of this region in the context of viral replication, we constructed several of these LS mutations (-201 to -184, -183 to -166, -165 to -148, and -148 to -130) in proviruses and prepared viral stocks by cocultivation of transfected RD cells with CEMx174 cells. In addition, two mutations between -93 and -76 and between -75 and -58 were utilized, since they affect the nuclear factor kappa B (NF-kappa B)- and Sp1-binding sites and were expected to diminish viral replication. Our results suggest that while transfection analyses offer an adequate approximation of the effects of the LS mutations, the analysis of viral replication using a mutant viral stock presents a more accurate picture, which is sometimes at variance with the transfection results. Three mutants (-201/-184 NXS, -165/-148 NXS, and -147/-130 NXS) had effects on viral replication that were much more severe than the effects predicted from their performance in transfection analyses, and the effects of two LS mutations (-201/-184 NXS and 183/-166 NXS) were not predicted by their effects in transfection. In addition, we observed cell type-specific permissiveness to replication of some mutant viruses. In the cell types tested, the LS mutations indicated an apparent requirement not only for the intact NF-kappa B and SP1-binding sites but also for several regions between -201 and -130 not previously associated with viral infectivity. PMID- 8437236 TI - Cell-dependent requirement of human immunodeficiency virus type 1 Vif protein for maturation of virus particles. AB - A highly sensitive single-round infection assay using a bacterial chloramphenicol acetyltransferase was developed to analyze an early stage of human immunodeficiency virus type 1 replication. By a combination of transfection and single-round infection assay, a virus with a vif mutation, depending on host cells from which the virus was derived, was demonstrated to be defective at the early phase of infection cycle. Analysis of viral proteins synthesized in cells indicated that incorporation of the Env surface protein into virions of the vif mutant, again in a cell-dependent way, was greatly restricted. Taken together, it is concluded that the Vif protein acts through modulation of the Env protein in the virions, directly or indirectly, to enhance viral infectivity in a certain cell type. PMID- 8437237 TI - Proper maturation of the Japanese encephalitis virus envelope glycoprotein requires cosynthesis with the premembrane protein. AB - The role of the Japanese encephalitis virus (JEV) premembrane (prM) protein in maturation of the envelope (E) glycoprotein was evaluated by using recombinant vaccinia viruses encoding E in the presence (vP829) or absence (vP658) of prM. Immunofluorescence analyses showed that E appeared to be localized in the endoplasmic reticulum of cells infected with JEV, vP829, or vP658. However, reactivity with monoclonal antibodies and behavior in Triton X-114 indicated that E produced in the absence of prM behaved abnormally. Furthermore, E produced in the presence of prM by recombinant vaccinia viruses could be incorporated into flavivirus pseudotypes, whereas E synthesized in the absence of prM could not. These results demonstrate that cosynthesis of prM is required for proper folding, membrane association, and assembly of the flavivirus E protein. PMID- 8437238 TI - Disulfide bond formation in the human immunodeficiency virus type 1 Nef protein. AB - Substitution of alanine for cysteine residues of the human immunodeficiency virus type 1 LAI (BRU) and ELI Nef proteins was used to determine pairing of the cysteine residues present in each protein. The results show that under nonreducing conditions, alternative pairing of the cysteines occurs. The preferred pairing of cysteine residues of the LAI and ELI proteins differs. In the experimental system used, viruses carrying the ELI nef allele are found to express Nef proteins which accelerate virus replication. Mutation in critical cysteine residues of the protein reduce the rate of virus replication. In the same system, viruses harboring the LAI nef allele fail to replicate. These observations raise the possibility that differences in the observed biological activity of nef alleles may be attributed, at least in part, to differences in the secondary structure of the proteins. PMID- 8437239 TI - The human gamma interferon receptor accessory factor encoded by chromosome 21 transduces the signal for the induction of 2',5'-oligoadenylate-synthetase, resistance to virus cytopathic effect, and major histocompatibility complex class I antigens. AB - Mouse fibroblasts, and human-mouse hybrid fibroblasts carrying only human chromosome 21, were transfected with cDNA encoding full-length human gamma interferon (IFN-gamma) receptor or chimeric IFN-gamma receptor (extracellular domain of the human receptor; transmembrane and intracellular domains of mouse origin). These transfected mouse cells were sensitive to human IFN-gamma only when human chromosome 21 was present. These results show that the species specific accessory protein encoded by human chromosome 21 interacts with the extracellular domain of human IFN-gamma receptor and transduces the IFN-gamma signal not only for up-regulation of mouse major histocompatibility complex class I antigen expression but also for the induction of 2',5'-oligoadenylate synthetase and resistance to virus cytopathic effect. PMID- 8437240 TI - Simian immunodeficiency virus-specific CD8+ lymphocyte response in acutely infected rhesus monkeys. AB - To assess the possible role of cytotoxic T lymphocytes (CTLs) in containing the spread of human immunodeficiency virus in acutely infected individuals, the temporal evolution of the virus-specific CD8+ lymphocyte response was defined in simian immunodeficiency virus of macaques (SIVmac)-infected rhesus monkeys. A brief period of SIVmac plasma antigenemia was seen 9 to 16 days following intravenous infection with SIVmac, ending as the absolute number of CD8+ peripheral blood lymphocytes (PBLs) increased. In a prospective assessment of the ability of CD8+ lymphocytes of these monkeys to suppress SIVmac replication in autologous PBLs, inhibitory activity was detected as early as 4 days, with a more pronounced effect 12 to 16 days following infection. SIVmac Gag- and Nef-specific CD8+ effector cell activities were demonstrable in PBLs of animals by 2 weeks following virus inoculation. In fact, SIVmac-specific CTL precursors were documented in the PBLs of rhesus monkeys 4 to 6 days after SIVmac infection. These studies indicate that AIDS virus-specific CD8+ CTLs are present in PBLs within days of infection and may play an important role in containing the early spread of virus. PMID- 8437242 TI - Sequence similarity between Borna disease virus p40 and a duplicated domain within the paramyxovirus and rhabdovirus polymerase proteins. PMID- 8437241 TI - Replication and persistence of simian immunodeficiency virus variants after passage in macaque lymphocytes and established human cell lines. AB - In lentivirus infections, there are typically few cells in the host that harbor the provirus. For this reason, molecular clones of human and simian immunodeficiency viruses (HIV and SIV) are generally derived after passage and amplification of the virus in cell culture. To determine whether SIV variants that persist in culture are similar to the variants that predominate in the host, we examined the proviral sequence of the SIV envelope (env) gene before and after cocultivation of lymphocytes from a macaque with AIDS with naive macaque lymphocytes or human cell lines. Many of the predominant variants in the monkey replicated and persisted in macaque lymphocytes and CEMx174 cells in culture, but a more limited population of variants replicated in C8166 cells. Passage of virus, harvested after 4 weeks of coculture, onto naive cells further demonstrated that the majority of proviruses detected by polymerase chain reaction were also viral variants that were expressed and packaged into infectious virions. PMID- 8437243 TI - The immunobiology and clinical use of current immunosuppressive therapy for renal transplantation. PMID- 8437244 TI - Combination therapy for staghorn calculi in solitary kidneys: functional results with long-term followup. AB - A total of 10 patients with staghorn calculi in a solitary kidney was managed with endourological sandwich therapy consisting of primary percutaneous debulking followed by extracorporeal shock wave lithotripsy (ESWL*) of residual inaccessible stones. Secondary percutaneous procedures, ESWL and chemical dissolution were used as necessary in a vigorous attempt to render each patient stone-free. As such, these 10 renal units underwent 21 percutaneous procedures through 13 tracts, 17 ESWL treatments and 3 courses of hemiacidrin. No patient required open operative intervention or dialytic support. With 4 to 57 months (mean 31.6) of followup, renal function for the group as a whole improved as evidenced by a decrease in mean serum creatinine levels from 3.1 mg./dl. before treatment to 2.2 mg./dl. at latest followup. More importantly, renal function has remained stable or improved in 9 of the 10 patients individually. We conclude that an aggressive, combined endourological approach to the management of staghorn calculi provides long-term preservation of function in the affected kidney. PMID- 8437245 TI - Results of 212 consecutive endopyelotomies: an 8-year followup. AB - Between 1983 and 1991 we performed 212 endopyelotomies on 110 cases of primary and 102 of secondary obstruction of the ureteropelvic junction. Of the 189 patients in the series 89% have been followed for a minimum of 6 months postoperatively, 63% for more than 3 years (3 to 8-year followup). Our overall success rate has been 86% with little difference being detected between the success that we have obtained with primary and secondary obstructions (85% versus 86%). Other variables, such as patient age, sex or side of obstruction, have little bearing on the outcome of the procedure. Endopyelotomy is passing the test of time as a safe and reliable means to correct ureteropelvic junction obstruction. Endopyelotomy should be the first choice for the correction of ureteropelvic junction obstruction in most patients. PMID- 8437246 TI - Intrarenal bacillus Calmette-Guerin therapy for upper urinary tract carcinoma in situ. AB - Of 17 renal units from 11 patients treated with intrarenal bacillus Calmette Guerin (BCG) for positive selective upper tract urine cytology 16 had negative radiographic studies and 1 had a papillary renal pelvic lesion. The standard diagnostic maneuvers were used to rule out other sources of positive cytology from the lower tracts. Six patients had bilateral involvement, 3 had prior contralateral nephroureterectomy and 2 had unilateral positive cytology but were poor surgical risks. The BCG solution was administered weekly by retrograde ureteral catheterization and instillation during 1 hour. One patient had fever during the initial treatment and received antituberculous therapy. Other side effects included transient hematuria in 3 patients and irritative urinary symptoms in most patients. Of 11 patients (12 renal units) 8 had normalization of the urinary cytology with a median followup of 36 months. One patient had unilateral conversion of the cytology result but the contralateral papillary tumor persisted, requiring nephroureterectomy. The remaining 2 patients had persistently positive cytology results and the disease progressed. Longer followup and further experience with intrarenal BCG are required before the exact role of this treatment modality in upper tract urothelial malignancies, including carcinoma in situ, can be determined. PMID- 8437247 TI - Conservative renal surgery for renal cell carcinoma in von Hippel-Lindau's disease. AB - A total of 19 patients with renal cell carcinoma associated with von Hippel Lindau's disease is described. Of the 7 patients with unilateral disease of low grade and stage 6 were treated with a renal sparing operation and 1 with radical nephrectomy. They had no evidence of disease during followup of up to 12 years (mean 4.8 years). Of the 12 patients with bilateral disease 3 presented with tumors of low grade and stage, and were treated successfully with a conservative operation. In the remaining 9 patients disease of high grade and stage had progressed and 6 died. Conservative renal operation is best suited for the typical tumor of low grade and stage, and preferably unilateral disease, associated with von Hippel-Lindau's disease. For bilateral disease of low grade and stage a similar conservative approach may be considered with caution. However, in the presence of high stage and multicentric tumors, most patients with bilateral tumors are probably better served by radical nephrectomy and subsequent renal replacement therapy. PMID- 8437248 TI - The natural history of interstitial cystitis: a survey of 374 patients. AB - A survey directed at determining the natural history of interstitial cystitis was conducted at our clinic. Information on demographics, risk factors, symptoms, pain and psychosocial factors was elicited from 374 patients who satisfied the National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases criteria for interstitial cystitis and had all been diagnosed as having interstitial cystitis by a urologist. With regard to demographics, patients were predominantly female (89.8%) and white (94.1%), with a mean age of 53.8 +/- 0.7 years (standard error) and age at the first symptoms of 42.5 +/- 0.8 years. Information on 25 potential risk factors included 44.4% of the women reporting hysterectomy, 38.2% of the patients having strong sensitivities or allergic reactions to medication and only 2.7% being diabetic. With regard to interstitial cystitis symptoms, frequency and urgency were reported by 91.7% and 89.3% of the patients, respectively, while pelvic pain, pelvic pressure and bladder spasms were reported by more than 60% of respondents and burning by 56%. Location and degree of pain were also reported. Urination relieved or lessened interstitial cystitis pain for 73.6% of the patients and medication was effective for 46.8%. Other behaviors (for example hot baths, heating pads, lying down or sitting) were less effective. Conversely, stress, constrictive clothing and intercourse increased interstitial cystitis pain in more than 50% of the patients. In addition, acidic, alcoholic or carbonated beverages, and coffee or tea increased interstitial cystitis pain in more than 50% of the patients. More than 60% of the patients were unable to enjoy usual activities or were excessively fatigued and 53.7% reported depression. Travel, employment, leisure activities and sleeping were adversely affected in more than 80% of the patients. Pain location and degree differed significantly between patients with and without ulcers in the bladder. In addition, there was an apparent plateau in the frequency and urgency among patients after approximately 5 years with symptoms. PMID- 8437249 TI - Management of abdominal aortic aneurysm and invasive transitional cell carcinoma of bladder. AB - Between January 1980 and June 1990 we treated 21 patients with invasive carcinoma of the bladder and abdominal aortic aneurysm. Three distinct groups of patients were identified. Group 1 comprised 8 patients who were initially diagnosed with invasive bladder cancer and during cancer staging a concomitant abdominal aortic aneurysm was found. Group 2 consisted of 10 patients previously treated for invasive bladder cancer who had aneurysmal disease at a later date. Group 3 included 3 patients who underwent a previous aneurysm repair and subsequently had invasive carcinoma of the bladder. Total survival was 9 of 21 patients (43%) with a mean of 84 months of followup after initial diagnosis. This finding is comparable to long-term (greater than 5 years) survival in patients with invasive carcinoma of the bladder alone. In fact, none of the 21 patients studied experienced rupture of the aneurysm and/or died of aneurysmal disease. We found that patients with abdominal aortic aneurysm and invasive bladder cancer have a poor overall prognosis. Although aneurysm repair presents technical challenges, mortality is dependent upon the carcinoma and other vascular or medical diseases, and does not bear direct relationship to abdominal aortic aneurysm. PMID- 8437250 TI - Treatment of brain metastases from bladder cancer. AB - The records of 28 patients with transitional cell cancer who had brain metastases were retrospectively reviewed. Data from 19 patients were considered suitable for analysis and were included in this study. One patient was treated with surgery alone, 10 with radiation alone and 7 with radiation and surgery, while 1 received no treatment. Mean and median survival times, respectively, were 57 and 42 months from the initial diagnosis, and 11 and 4 months from diagnosis of central nervous system metastases. Patients treated with surgery and radiation demonstrated a mean survival time of 19 months compared to 6 months for patients treated with radiation alone (p = 0.03). There were 2 long-term survivors in the combined modality group at 50 and at 12 months. Enthusiasm for combined modality treatment should be tempered by the fact that selection bias favored the combined modality group; 13 patients with single lesions demonstrated a mean survival of 14 months compared to 3 months for 6 patients with multiple lesions (p = 0.009) and only patients with solitary lesions underwent surgical resection. Brain metastases have an ominous prognosis in patients with bladder cancer primaries. Considering the sum of the retrospective and prospective reports, we recommend that patients with solitary brain lesions and good performance status be aggressively managed with surgical resection and postoperative radiation therapy. PMID- 8437251 TI - Above and below delayed endoscopic treatment of traumatic posterior urethral disruptions. AB - Between 1982 and 1990, 10 men with posterior urethral obliterations associated with pelvic fracture were managed with delayed above and below endoscopic reconstruction. After a mean of 43 months (range 7 to 108) of followup, all 10 men void with a peak flow rate of 12 ml. per second or greater and/or have a urethral caliber of 20F or greater. Concomitant prostatic hypertrophy somewhat compromises micturition in 4 older men. Nine patients are totally continent and 1 has mild stress incontinence. Five men who were potent after injury remain so after reconstruction. Of the 10 patients 6 required subsequent visual urethrotomy and/or scar resections, generally as outpatient or short stay procedures. In most instances voiding stabilized within 1 year, and interventions after this interval were unusual and generally trivial. We compare our experience with the results of others using a similar delayed endoscopic approach and conclude that this is a satisfactory method of managing traumatic posterior urethral obliterations, resulting in satisfactory voiding, continence and potency preservation. PMID- 8437252 TI - Reconstruction of extensive urethral strictures: circular fasciocutaneous penile flap. AB - The circular fasciocutaneous penile flap originates on the distal penis and uses Buck's fascia as the major vascular conduit. It is hairless, provides up to 15 cm. of length, adapts to the entire anterior urethra, can be used in circumcised men, and provides the opportunity for 1-stage reconstruction of complex anterior strictures with excellent functional and cosmetic results. The flap was used in 10 patients with complex strictures 8 to 21 cm. long: 1 substitution urethroplasty of 8 cm. and 9 onlay urethroplasties (2 of which used a free penile skin graft and a bladder mucosa graft as supplementation to bridge defects of 18 and 21 cm., respectively). All patients have normal erectile function. No dilations were required, no strictures have recurred (mean followup 14.4 months) and mean maximal urinary flow rates are normal (mean 21.7 ml. per second, range 18 to 30). PMID- 8437253 TI - Squamous cell carcinoma of the penis. III. Treatment of regional lymph nodes. AB - We analyzed the management of regional lymph nodes in 110 patients with squamous cell carcinoma of the penis treated at the Netherlands Cancer Institute between 1956 and 1989 with curative intent. Of 66 patients who presented with unsuspected nodes 57 were placed on a surveillance program, while lymph node dissection was performed in 5 (with adjuvant external radiation therapy in 1) and 4 were treated with external radiation therapy only. The management of 40 patients with clinically suspected nodes included surveillance in 5, lymph node dissection in 27 (with adjuvant radiotherapy in 11), biopsy in 4 and external radiation therapy in 4. Postoperative radiotherapy had been given if more than 2 nodes were involved or when extracapsular growth was observed. Overall, 25 patients had a regional recurrence, 5 of whom could be cured subsequently. All regional recurrences developed within 2 years after primary treatment. Analysis showed 100% survival in histologically proved node negative patients (stage pN0). The success of lymph node dissection was related to the extent of the metastatic spread and to the number of involved nodes. Patients with 1 positive node and unilateral inguinal involvement showed a statistically significant survival advantage compared to patients with more extensive spread. Considering the indications for node dissection we found a clear relationship among T category, grade and the probability of lymph node invasion. Patients with stage T1 tumors and stage T2, grades 1 and 2 tumors presented significantly less often with lymphatic invasion than those with other categories of disease and were less likely to have a regional recurrence after treatment of the primary tumor only. In these categories we recommend surveillance of the regional lymph nodes in patients who present with unsuspected nodes. However, patients with stage T2 grade 3, stage T3 and operable stage T4 tumors should undergo an immediate inguinal node dissection because of the high probability of clinically occult lymph node invasion (in our material more than 50%). With respect to the extent of the node dissection, we found that the likelihood of spread to the contralateral and/or pelvic regions was related to the number of invaded nodes in the inguinal region. We recommend contralateral node dissection and unilateral pelvic node dissection when 2 or more positive nodes are found in the dissected groin specimen. Primary pelvic node dissection should be performed in patients who present initially with cytologically or biopsy proved positive inguinal nodes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8437254 TI - Patterns of irrigating fluid absorption during transurethral resection of the prostate as indicated by ethanol. AB - The absorption of irrigating fluid was measured by the ethanol method every 10 minutes during the course of 700 transurethral prostatic resections. The total blood loss was also measured using a photometer method. We found that ethanol determination is a convenient method of monitoring irrigating fluid absorption in daily practice. Absorption in excess of 150 ml. was detected in 46% of the operations. The volume of irrigant absorbed increased with the weight of the removed prostatic tissue, operating time and blood loss. The uptake of fluid usually started midway through the operation. Once absorption had started, there was an 87% probability that it would continue through the next 10 minutes with the exception of the last 10 minutes of surgery, when there was a 67% probability. A sudden decrease in arterial pressure coincided with the onset of fluid absorption 3.7 times more often than expected by chance. The absorption was no different in the 114 patients with a cancerous histology, compared to those with benign prostatic hyperplasia. PMID- 8437255 TI - Risk factors for bacteriuria and clinical urinary tract infection in patients treated with clean intermittent catheterization. AB - To study factors that may predict the occurrence of bacteriuria and clinical urinary tract infection, a total of 302 patients using clean intermittent catheterization was followed. Bacteriuria was found equally in men and women, while clinical urinary tract infection was significantly higher among women. Predictive factors of clinical urinary tract infection were low age and high mean catheterization volume in women. In men low age, neurogenic bladder dysfunction and nonself-catheterization were predictors in addition to urine leakage in patients with neurogenic dysfunction. Bacteriuria was a risk factor of future clinical infection and bacteriuria. No other risk factor of bacteriuria could be identified in the female population, while low frequency of catheterization, high age and nonself-catheterization were predictive in men. Patients using anti infective agents had fewer episodes of bacteriuria but significantly more clinical urinary tract infections compared to nonusers. PMID- 8437256 TI - Single dose quinolone treatment in acute uncomplicated urinary tract infection in women. AB - A total of 125 ambulatory women (85 premenopausal and 40 postmenopausal) who experienced 174 acute urinary tract infections with mainly gram-negative bacteria (99%) was randomized to receive a single dose, 2-tablet treatment with either ofloxacin (400 mg.), norfloxacin (800 mg.) or ciprofloxacin (500 mg.). Cure was achieved in 163 of the 174 acute episodes (94%). More specifically, the cure rates were 97% (57 of 59 infections) with ofloxacin, 96.5% (56 of 58) with ciprofloxacin and 88% (50 of 57) with norfloxacin. While the initial cure rate of the acute urinary tract infections was 96% (112 of 117) in the premenopausal group, it reached only 90% (51 of 57) in the postmenopausal group. The 17 urinary tract infections that followed the initial 2-tablet quinolone treatment were cured by either an additional single dose, 2-tablet treatment with a different quinolone in 6 cases, a 1-day treatment with other adequate antibacterials in 9 and a 7-day treatment in 2. The 2-tablet quinolone treatment proved to be an effective, easy and cost-effective treatment for acute urinary tract infections in premenopausal and postmenopausal women. PMID- 8437257 TI - A simple technique for intraoperatively stenting a transected ureter. AB - We present a simple technique for intraoperative stenting of a transected ureter. This method does not require cystoscopy, or a separate incision in the bladder or skin. PMID- 8437258 TI - Ventral penile approach in unitary component penile prosthesis placement. AB - We report the results of a series of 79 patients who underwent placement of a unitary component penile prosthesis via a ventral penile skin incision in conjunction with distal ventral corporotomies. This approach facilitates the placement of semirigid and inflatable devices, and eliminates potential pitfalls of other incisions by limiting corporotomy length, avoiding dissection around neurovascular structures and allowing a multilayered closure with nonoverlapping suture lines. PMID- 8437259 TI - Detrusor function with lesions of the cauda equina, with special emphasis on the bladder neck. AB - A total of 13 patients with proved lesions of the cauda equina underwent neurological evaluation. All patients had video urodynamic testing, while 9 underwent a varying combination of pelvic floor electromyography, lumbosacral evoked potentials to tibial nerve stimulation and the sympathetic skin response from the perineum. All patients had detrusor areflexia with varying degrees of bladder neck incompetence. Reports of clinical and experimental studies are discussed in relation to the pathophysiology of bladder neck function following lesions of the pudendal and preganglionic pelvic nerve to explain why there have been conflicting reports in the literature regarding bladder neck function with lesions of the cauda equina. The adaptive changes observed in the experimental animal, consisting of random regeneration of the cholinergic neuroeffective junctions, adrenergic hyperinnervation and an increased sensitivity of the prejunctional inhibitory muscarinic receptors on the adrenergic nerve, may explain the degree of variability of bladder neck incompetence observed clinically. PMID- 8437260 TI - Unilateral occlusion of duplicated mullerian ducts associated with ipsilateral Gartner's duct cyst: report of 3 cases. PMID- 8437261 TI - Major blunt renal trauma in the pediatric population: is a nonoperative approach indicated? AB - We evaluated and treated at our institutions 22 consecutive patients with major blunt renal trauma: 20 had major renal lacerations (grades 3 to 5) as defined by initial computerized tomography, and 2 had vascular pedicle injuries without parenchymal injury and were excluded. An attempt was made to treat all children with a nonoperative approach. Two patients (10%) required renal exploration: 1 for persistent bleeding and 1 in whom a renal neoplasm could not be excluded. The remaining 18 patients (90%) were stabilized and observed. No child required delayed renal exploration. All traumatized renal units demonstrated function on followup studies. Hypertension did not occur in the 13 patients available for long-term followup. We conclude that nonoperative management is a suitable alternative to early exploration in children with major blunt renal lacerations. PMID- 8437262 TI - A single center experience with renal transplantation in young children. AB - Results of pediatric renal transplantation have been variable. We evaluated our experience with renal transplantation in children less than 5 years old to determine its safety and efficacy. Of the 428 renal transplants done at our institution from August 1983 to December 1989, 14 were performed in 13 children 13 to 50 months old (mean age 34 months). All of the patients were small for age with height standard deviation scores ranging from -1.7 to -4.5. Patient survival, allograft survival and statural growth were used as determinants of successful outcome. Followup was complete in all patients, including renal function studies and serial height measurements. Growth velocity standard deviation scores were calculated. Patient survival was 100%. Allograft survival was 100% 2 to 7.3 years after transplantation for living related donor recipients whereas 1-year graft survival was poor (40%) for cadaveric graft recipients. Of 10 patients with good graft function at 1 year 9 demonstrated improvement in the height standard deviation score. Seven of 10 patients demonstrated significant catch-up growth (growth velocity standard deviation score greater than 0, p = 0.04). Our study supports the safety and efficacy of renal transplantation in young children. Early transplantation using living-related donor organs is the optimal therapy to prevent growth retardation and allow the young child with end stage renal disease to have a normal life. PMID- 8437263 TI - Sonographic evaluation of ureterectasis in children: the significance of peristalsis. AB - The presence or absence of ureteral peristalsis was noted during real-time sonography of 61 dilated ureters in children. The findings were correlated with diagnoses established using standard radiographic and radionuclide imaging techniques. Of the 47 dilated ureters that exhibited peristalsis 44 were classified as not obstructed when assessed with standard imaging and functional studies. The most frequent etiology for ureteral dilatation associated with peristalsis was high grade vesicoureteral reflux (31 ureters). Three peristaltic ureters were shown to be mildly to moderately obstructed. Absence of peristalsis was noted in 14 ureters: 13 were severely obstructed, while in 1 the involved kidney had no function. In the pediatric age group the demonstration of peristalsis in a dilated ureter is frequently associated with vesicoureteral reflux and is seldom associated with obstruction. Obstruction, if present, usually is mild. Aperistaltic ureterectasis implies severe obstruction or poor renal function. PMID- 8437264 TI - Endoscopic incision of ureteroceles: intravesical versus ectopic. AB - A total of 51 children, mostly less than 2 years old, underwent endoscopic incision of ureteroceles as a primary form of treatment. In 73% no further surgery was required. Of the patients 19 were diagnosed by prenatal ultrasound, with a urinary tract infection the usual presenting symptom in the remainder. Of 27 intravesical cases endoscopic incision resulted in decompression of the ureterocele in 93%, with preservation of upper pole function in 96%, and secondary surgical procedures were required in 7%. Reflux was created in 18% and it persisted in 2 of 4 patients. Of 24 cases of ectopic (extravesical) ureteroceles incision resulted in decompression in 75%, with upper pole function preserved in 50%. Reflux was created in 47% and a secondary surgical procedure was performed in 50%. Preservation of upper pole function was significantly better for intravesical versus ectopic ureteroceles (p < 0.01), and the requirement for secondary surgical procedure was greater with ectopic ureteroceles (p < 0.01). Three patients had intermittent bladder outlet obstruction following the incision and required further surgery. The 2 different techniques for incision of intravesical and ectopic ureteroceles are described. The role of endoscopic incision in the overall management of ureteroceles is confirmed by this review, and the need for partial nephroureterectomy may diminish. PMID- 8437265 TI - What volume can a child normally store in the bladder at a safe pressure? AB - To determine what volume a child can normally store in the bladder at a safe pressure 923 pediatric urodynamic studies were reviewed, and 69 examinations done on 17 boys and 52 girls were considered normal. Patient ages were recorded and body surface areas were calculated. A continuous intermediate flow water cystometrogram had been performed. Total bladder capacity in milliliters, full resting pressures (cm. water), and the volumes (milliliters) and percentages of the total bladder capacity stored at detrusor pressures of less than 10, 20, 30 and 35 cm. water were measured. We found that 98.1% of the total bladder capacity could be stored at a detrusor pressure of less than 20 cm. water in more than 95% of the children independently of age or body surface area and 99.9% could be stored at a detrusor pressure of less than 30 cm. water. An approximation of the minimal acceptable total bladder capacity for age can be calculated by 16(age) + 70 in ml. According to our results, we proposed criteria for good storage characteristics of the bladder in children. PMID- 8437267 TI - Appendicovesicostomy (and variations) in bladder reconstruction. AB - Bladder reconstruction using bowel segments was advanced when intermittent catheterization proved so acceptable. Access to the reservoir by way of the urethra is often not possible in children, especially boys. Implantation of the isolated appendix into the bladder remnant or colon segment similar to a ureteral reimplant provides a continence mechanism with ready catheter access (the Mitrofanoff principle). Since 1982 we have applied this principle in 41 pediatric cases of bladder reconstruction (64% boys). Primary diagnoses included bladder exstrophy (46%) and myelomeningocele (34%). Extending the concept of a flap valve continence channel with a narrow tube into the reservoir, segments of tapered ileum and ureters were also used (appendix 61%, ileum 12%, ureter 27%). Results of continence (100%) and uncomplicated catheterization (93%) have been satisfactory. Unfortunately, the longer the experience (average 3.2 years of followup), the more stone formation we experienced (32%), which is due to mucus production and bacteriuria as the stone nidus. There were 2 deaths, including 1 from a renal stone obstructing the ureter with sepsis and 1 a likely suicide. Reoperation was required for 3 stomal revisions, 2 bowel obstructions and 7 stone removals in 3 of the 6 cases in which the bladder neck was closed. Unique aspects of these reconstructions are presented, such as our current preference to bury the stoma in the umbilicus (7 cases), placement of the ureteral segment into the perineum as a neourethra and an unusual conjoined twin reconstruction. PMID- 8437268 TI - Urological manifestations of sacrococcygeal teratoma. AB - A review was done of 29 patients diagnosed with sacrococcygeal teratoma between 1978 and 1991. Urological disorders included total urinary retention (6 patients), hydronephrosis (6), hydrocele (4) and undescended testis (1). Ultrasonography and voiding cystourethrography were performed on the 6 patients in total urinary retention. These studies revealed cystic retrorectal lesions frequently with intralesional calcifications, and anterior and superior displacement of the bladder. Bladder wall trabeculation occurred in 2 of these 6 patients, and 4 had moderate or severe hydronephrosis. Upper urinary tract dilatation was found in 2 patients not in total retention. Hydronephrosis appeared to be related to poor bladder emptying and presumably high intravesical pressures, since each case resolved spontaneously after tumor resection. No primary upper tract anomalies were identified. PMID- 8437266 TI - Adenovirus-associated hemorrhagic cystitis treated with intravenous ribavirin. AB - Adenovirus hemorrhagic cystitis following bone marrow transplantation occurs in 2 to 16% of the patients. While usually self-limiting, this disease can cause significant morbidity and even mortality in the immunocompromised patient. Risk factors include graft versus host disease and pre-transplant seropositivity to adenovirus. Standard treatment of this disorder consists of hydration, diuresis and analgesics. Failure of these measures leads to multiple blood transfusions, severe patient morbidity and possible death. When conservative therapy is unsuccessful, there is no proved standard of care. We recently used ribavirin, a broad-spectrum antiviral agent against adenovirus infection in vitro, to treat refractory adenovirus hemorrhagic cystitis after bone marrow transplantation. The hematuria and urinary symptomatology resolved without demonstrable side effects. We present ribavirin as a therapeutic alternative when conservative treatment for adenovirus hemorrhagic cystitis fails. PMID- 8437269 TI - Hydatid disease of the urinary tract. AB - Hydatid disease of the urinary tract is uncommon, accounting for only 2 to 3% of all such cases. We report 2 cases of urinary tract hydatidosis, of which 1 was associated with disseminated disease and 1 with isolated renal hydatid disease. We describe the variety in presentation, manifestations and symptoms of the disease, and discuss radiological evaluation and findings. PMID- 8437270 TI - Eosinophilic cystitis caused by vesical sparganosis: a case report. AB - We report a case of eosinophilic cystitis caused by vesical sparganosis. The patient had a history of eating raw frogs and presented with a mass in the bladder associated with peripheral eosinophilia and increased serum antibody titer against sparganum. Pathologically, a characteristic sinuous necrosis representing worm tracks was noted with massive diffuse infiltration of eosinophils in the wall of the bladder. The serum titer of sparganum-specific antibody returned to normal after surgical resection of the lesion. This finding emphasizes the importance of suspecting parasitic origin in cases of eosinophilic cystitis with a history of raw meat ingestion in endemic areas. PMID- 8437271 TI - Tuberculous spondylitis as a complication of intravesical bacillus Calmette Guerin therapy. AB - We report a case of tuberculous spondylitis following intravesical bacillus Calmette-Guerin (BCG) instillation. A 90-year-old male physician living in South Africa received an uncomplicated 6-week course of intravesical BCG (Japanese 172 strain) for high grade superficial bladder carcinoma. He experienced a sudden onset of debilitating lower back pain 16 months following this treatment. A lytic lesion involving the anterior T11 and T12 vertebral bodies was diagnosed and subsequently biopsied. An acid-fast organism was isolated after 3 weeks of incubation and was confirmed through deoxyribonucleic acid probe hybridization as a mycobacterium. High performance liquid chromatography analysis speciated the organism as Mycobacterium bovis BCG, proving that it was acquired through the intravesical therapy. PMID- 8437272 TI - Squamous cell carcinoma of the bladder associated with cyclophosphamide therapy for Wegener's granulomatosis: a report of 2 cases. AB - Cyclophosphamide has been used to treat a variety of malignant and nonmalignant diseases. The association of this agent with the development of urothelial tumors has been well documented. Although most bladder cancers associated with prior cyclophosphamide therapy are transitional cell carcinoma, to our knowledge there have been 6 reports of cyclophosphamide-induced squamous cell carcinoma of the bladder. We report 2 additional cases of squamous cell carcinoma of the bladder that occurred in patients after cyclophosphamide treatment for Wegener's granulomatosis. Any patient with a history of prolonged cyclophosphamide ingestion needs careful long-term monitoring of the lower urinary tract, since there is at least a 9-fold increase in the incidence of lower urinary tract malignancy in such patients. PMID- 8437273 TI - The use of rotated vascularized pedicle flaps for complex transvaginal procedures. AB - We report the use of relatively simple rotated vascularized pedicle flaps to assist in the closure of complex vaginal procedures. The Martius, labial and buttock flaps are described, and should be included in the armamentarium of the urological surgeon. PMID- 8437275 TI - Cavernous artery obstruction following blunt trauma to the penis. AB - Erectile dysfunction following blunt trauma to the erect penis usually is associated with an injury to the tunica albuginea of the corpus cavernosum. We recently identified 2 patients with erectile dysfunction following bending of the penis during coitus whose only abnormality after a complete evaluation, including penile angiography, was a deep cavernous artery injury. We suggest that during examination of patients with erectile dysfunction following blunt injury to the erect penis a complete vascular evaluation, including penile angiography, may be necessary to detect an unrecognized injury to the deep cavernous arteries. PMID- 8437274 TI - Prosthesis placement after total phallic reconstruction. AB - Total reconstruction of the phallus is now technically feasible. The successful reestablishment of sexual function in these patients is possible using the neurosensory radial forearm flap. The innervated neophallus develops tactile and erogenous sensation within 4 to 6 months of neurorrhaphy. Unperceived chronic pressure with subsequent tissue ischemia is the leading cause of delayed prosthesis extrusion. The development of protective sensation within this reconstructed neophallus allows for the safe placement of a penile prosthesis permitting intromission. The development of erogenous sensation allows for orgasm. We report on the successful implantation and long-term retention of penile prostheses in 4 patients after total phallic reconstruction. PMID- 8437276 TI - A spermatic cord hematoma secondary to varicocele rupture from blunt abdominal trauma: a case report and review. AB - Varicocele is a relatively common entity that is mostly studied because of the effects on the testes and a presumed role in infertility. Hemorrhage secondary to a varicocele, however, is a known but rare morbidity. A case is presented of a ruptured varicocele due to blunt abdominal trauma with a sudden increase in intra abdominal pressure with transmission to the varicocele. Such a mechanism may also provide an explanation for the occurrence of a more commonly recognized phenomenon of idiopathic spermatic cord hematoma. PMID- 8437277 TI - An incompletely identified combined urogynecological malformation presenting as anuria. AB - We report on an 18-year-old woman with a combined urogynecological malformation who presented with anuria. At the age of 8 years she presented elsewhere with urometrocolpos secondary to a left hypoplastic kidney and an ectopic ureter that inserted into the vagina. A retroiliac right ureter also was identified. She underwent surgical treatment and was reported in the urological literature. At menarche she began to have severe dysmenorrhea. After multiple hospitalizations elsewhere without diagnosis she presented to our emergency room with anuria. The anuria was the direct result of additional, previously unidentified malformations, consisting of uterus duplex bicollis and vaginal hypoplasia. We emphasize the importance of identifying all components of the genital and urological systems whenever anomalies are present in either system. PMID- 8437278 TI - Crystallization kinetics of calcium oxalate in fresh, minimally diluted urine: comparison of recurrent stone formers and healthy controls in a continuous mixed suspension mixed product removal crystallizer. AB - A reproducible method has been developed for studying calcium oxalate crystallization from fresh, minimally diluted (92%) urine with the mixed suspension mixed product removal continuous crystallization technique. All samples were adjusted to give the same starting calcium and oxalate concentrations. Twenty-one recurrent male stone formers were compared with twenty two healthy controls. There was no difference in crystal growth rates but crystal nucleation rates were much higher in the control group (p = 0.003). Using growth rate and nucleation rate results, the amount of crystalline material in suspension was shown to be lower in the urine from stone formers, and therefore the equilibrium supersaturation in the crystallizer was lower in the control group (p = 0.001). We propose that the ability of a healthy person's urine to maintain a lower supersaturation is a crucial protective factor distinguishing non-stone formers from stone formers. PMID- 8437279 TI - Studies of the hormonal control of postnatal testicular descent in the rat. AB - Dihydrotestosterone is believed to control the transinguinal phase of testicular descent based on hormonal manipulation studies performed in postnatal rats. In the present study, these hormonal manipulation experiments were repeated, and the results were compared with those obtained using the antiandrogens flutamide and cyproterone acetate. 17 beta-estradiol completely blocked testicular descent, but testosterone and dihydrotestosterone were equally effective in reversing this inhibition. Neither flutamide nor cyproterone acetate prevented testicular descent in postnatal rats despite marked peripheral antiandrogenic action. Further analysis of the data revealed a correlation between testicular size and descent. Androgen receptor blockade did not produce a marked reduction in testicular size and consequently did not prevent testicular descent, whereas estradiol alone caused marked testicular atrophy and testicular maldescent. Reduction of the estradiol dosage or concomitant administration of androgens or human chorionic gonadotropin resulted in both increased testicular size and degree of descent. These data suggest that growth of the neonatal rat testis may contribute to its passage into the scrotum. PMID- 8437280 TI - Laparoscopic implantation of electrodes for stimulation of the hypogastric nerve and the vas deferens in dogs. AB - The minimal invasiveness of laparoscopy prompted us to investigate its use for placement of electrodes for stimulation of the hypogastric nerve and the vas deferens. In an acute canine model, pressure changes in the vas deferens secondary to electrostimulation were recorded. The laparoscopic approach included four ports. Monopolar cuff electrodes were placed around the hypogastric nerve and the vas deferens, and the leads of both were pulled through the abdominal wall. After multiple percutaneous stimulations (20 mAmp., 20 Hz. and 200 microsecond pulse width), the abdomen was opened through a midline incision to check the position of the electrodes. Electrostimulation was repeated with the abdomen open. Electrostimulation of both the hypogastric nerve and vas deferens resulted in marked pressure rises in the vas. These increases were similar in response to both surface and percutaneous stimulation. We thus believe that laparoscopic implantation of electrodes followed by percutaneous preliminary stimulation of the superior hypogastric plexus or the vas deferens may be a viable future approach to anejaculation. PMID- 8437281 TI - Electrical stimulation of the dorsal nerve of the penis evokes reflex tonic erections of the penile body and reflex ejaculatory responses in the spinal rat. AB - An animal model using the spinal rat was characterized. Electrical stimulation of the dorsal nerve of the penis elicited reflex tonic erections of the penile body and reflex bulbospongiosus muscle activity, flips and ejaculations. The tonic erections of the penile body are independent from contractions of the bulbospongiosus muscle and appear to be the result of a neurovascular process. Our observations suggest that reflex bulbospongiosus muscle activity, flips and ejaculations are a single complex reflex response, which we define as reflex ejaculatory response. Two parameters predicted the occurrence and type of reflex response. The visualization of bulbospongiosus muscle activity during surgical isolation of the dorsal nerve of the penis was sufficient to anticipate the elicitability of reflex ejaculatory responses. The latter, together with a systemic systolic pressure > or = 73 mmHg., warranted the elicitability of reflex tonic erections. The similarities found in the physiology of rat tonic penile body erections and of human erections make this model promising for further elucidation of sexual function. Moreover, the present model may prove useful for the investigation of neurogenic erectile dysfunction, and of neurogenic ejaculatory disorders. PMID- 8437282 TI - The effects of focused extracorporeal pyrotherapy on a human bladder tumor cell line (647 V). AB - Human transitional cell bladder carcinoma cell-line 647 V has been used to evaluate the effects on tumor cells in vitro of a new technique: focused extracorporeal pyrotherapy (F.E.P.). The device is made of multi-sources of piezoelectric ceramics focused at 320 mm. The focal area is 10 mm. high on 1.5 mm. width, and shots of 0.25 to 0.50 seconds were delivered on 4 groups of cell pellets placed in a polyurethane tube at the focus. Trypan blue MTT cell growth curve and Colony forming tests were used. There was a significant reduction (Student's t test) of the cell variability rate on the Trypan Blue test, 5% (in the treated Group) against 95% (control Group). The growth curve was flattened whether 0.50 second shots were single or repeated. The colony formation test was also significantly altered: 5.7% (treated group) against 70% (control group). CONCLUSION: focused extracorporeal pyrotherapy is able to alter or kill tumor cells in vitro. PMID- 8437283 TI - Immunotherapy of murine bladder cancer with keyhole limpet hemocyanin (KLH). AB - Keyhole limpet hemocyanin (KLH) is a potent immunogen that is being evaluated as an immunotherapeutic alternative to BCG in the treatment of bladder cancer. In the mouse bladder tumor model (MBT2) intralesional KLH significantly reduced tumor incidence, growth rate, and mortality and exhibited antitumor activity similar to that achievable with BCG. Endotoxin contamination of KLH was not responsible for the antitumor activity, although endotoxin alone was shown to have anti-tumor activity in this animal model. Keyhole limpet hemocyanin is both safe and effective in the MBT2 model, and is an immunomodulator to consider for clinical trials. PMID- 8437284 TI - Morphologic and functional alterations of intestinal segments following urinary diversion. AB - The current study was undertaken to determine the effect of chronic urinary diversion on both the morphology and absorptive function of intestine. Adult female Wistar rats (N = 8) underwent urinary diversion by interposing a 10-12 cm. segment of distal ileum between the bladder and sigmoid colon following urethral ligation. Control animals (N = 8) underwent sham laparotomies. Three months later, the diverted segment and a 10-12 cm. segment of distal ileum in control animals were studied. The intestinal segments were studied morphologically by both light microscopy and transmission electron microscopy. By using a previously reported in vivo intestinal perfusion model, the transport properties of the intestinal segments were examined. There were prominent and consistent morphological alterations in the diverted segments when compared with normal ileum. These changes consisted of marked mucosal atrophy evidenced by loss of microvilli with decreased villi-to-crypt ratio in diverted segments. Diverted ileum secreted more sodium and absorbed less chloride than normal ileum though this difference was not statistically significant. Water flux into the intestinal lumen was higher in diverted bowel (p = .06). The absorption of ammonium, potassium, and urea, as well as bicarbonate secretion, was the same in the diverted ileum as in normal ileum. There was also no significant difference in pH change or osmolar flux between the two groups. In conclusion, the results of this study indicate that despite morphological changes as a result of chronic exposure of urine, intestinal segments continue to transport urinary solutes similar to normal nondiverted segments. This represents the first convincing evidence that the reason for the low incidence of metabolic alterations following urinary diversion is not due to decreased absorptive capacity of the intestinal mucosa. PMID- 8437285 TI - The use of salicylic acid to prevent the adherence of Escherichia coli to silastic catheters. AB - We studied the effect of salicylic acid on the attachment of Escherichia coli to silastic catheters. Silastic catheters were exposed to organisms grown in the presence of subinhibitory concentrations (1 and 5 mM.) of salicylic acid. An agar rolling technique demonstrated 59% and 79% inhibition of adherence with the 2 concentrations, respectively. Silastic catheters were also pretreated by heating and then incubating in 200 mM. and 600 mM. salicylic acid in 95% ethanol at -20C. After incubation in 10(4) CFU/ml. E. coli for 5 hours at 37C, 62% and 93% inhibition of adherence was observed. Acetylsalicylic acid and ibuprofen did not demonstrate similar results. Similar inhibition (82% and 95%) was observed despite preincubation of the treated catheters in sterile urine for 4 days. A bioluminescent assay of bacterial adherence also revealed inhibition only with salicylic acid. Studies using 3H-leucine demonstrated a decrease in adherence with higher concentrations of salicylic acid. Finally, tridodecylmethylammonium was used to bind salicylic acid to silastic catheters. After a 5-hour incubation in 10(4) CFU/ml. at 37C, 94% and 99% inhibition were observed with 200 and 600 mM. salicylic acid. Salicylic acid decreases adherence of E. coli to silastic catheters. This observation may be of value in designing catheters less likely to cause urinary tract infection. PMID- 8437286 TI - Influenza's distant early warning system. PMID- 8437287 TI - Domestic violence hot line's demise: what's next? PMID- 8437288 TI - Revised Justice Department rule does not require physician participation in federal executions. PMID- 8437289 TI - While national domestic violence hot line's down, other resources can assist physicians, patients. PMID- 8437290 TI - Clinton tinkers with health system status quo; critics seek to pick apart managed competition. PMID- 8437291 TI - Most US troops may leave Somalia by May; military medicine still likely to have role. PMID- 8437293 TI - 98.6 degrees F. PMID- 8437292 TI - From the Centers for Disease Control and Prevention. Recommendations for use of folic acid to reduce number of spina bifida cases and other neural tube defects. PMID- 8437294 TI - 98.6 degrees F. PMID- 8437295 TI - 98.6 degrees F. PMID- 8437296 TI - 98.6 degrees. PMID- 8437297 TI - 98.6 degrees F. PMID- 8437298 TI - Underdosing the antidote for acetaminophen. PMID- 8437299 TI - Evidence-based medicine: a new paradigm for the patient. PMID- 8437300 TI - Evidence-based medicine: a new paradigm for the patient. PMID- 8437301 TI - Does magnesium prevent myocardial infarction? PMID- 8437302 TI - Periconceptional folic acid exposure and risk of occurrent neural tube defects. AB - OBJECTIVES: A recent controlled trial has established that use of a 4-mg folic acid supplement before and during early pregnancy reduces the risk of recurrent neural tube defects (NTDs) by 72%. The present study was designed to determine whether folic acid also reduces the risk of first (occurrent) NTDs. DESIGN: Case control study. SETTING: Tertiary and birth hospitals in metropolitan areas of Boston, Mass, Philadelphia, Pa, and Toronto, Ontario. PARTICIPANTS: Mothers of 436 occurrent cases with NTDs and mothers of 2615 controls with other major malformations. MAIN OUTCOME MEASURES: The prevalence of use of multivitamins containing folic acid was compared between mothers of cases and controls. RESULTS: The mothers of 17% of cases and 3% of controls reported knowledge of the folic acid-NTD hypothesis and were excluded from further analysis. For daily use of a multivitamins containing folic acid in the periconceptional period (28 days before through 28 days after the last menstrual period), the relative risk (RR) (and 95% confidence interval) was 0.4 (0.2 to 0.6). The most commonly used dose of folic acid was 0.4 mg, and the RR estimate was 0.3 (95% confidence interval, 0.1 to 0.6). For dietary folate, there was a dose-related decline in risk according to the quintile of intake (P for trend = .02). CONCLUSION: These findings suggest that daily periconceptional intake of 0.4 mg of folic acid (the dose most commonly contained in over-the-counter multivitamin preparations) reduces the risk of occurrent NTDs by approximately 60%. A relatively high dietary intake of folate may also reduce the risk. PMID- 8437303 TI - Accuracy of fecal occult blood screening for colorectal neoplasia. A prospective study using Hemoccult and HemoQuant tests. AB - OBJECTIVES: To define the validity of fecal blood as a marker for colorectal neoplasia in the screening setting and to compare yields by Hemoccult and HemoQuant fecal occult blood screening tests. DESIGN: A multicenter masked comparison of fecal blood test results against structural colorectal evaluations and longitudinal follow-up, serving as criterion standards, in nonreferred subjects at risk for colorectal neoplasia. SETTING: Communities, primary care centers, referral centers. PARTICIPANTS: Two groups: (1) 1217 patients aged at least 18 years undergoing routine structural surveillance evaluations following curative resection of a colorectal tumor and (2) 12312 relatives of colorectal cancer patients aged at least 50 years. INTERVENTIONS: Blinded Hemoccult II and HemoQuant testing on three mailed-in stool samples per subject. MAIN OUTCOME MEASURE: Sensitivity of fecal blood tests for colorectal neoplasia. RESULTS: In the postresection group, surveillance evaluations revealed 46 malignant colorectal neoplasms and 402 polyps. At matched specificity, sensitivity of either test for cancer was 26% (95% confidence interval, 13% to 39%). Hemoccult was positive in 21% of intraluminal recurrences, 33% of all new primary tumors, and 29% of Dukes A or B cancers; HemoQuant was elevated in 24%, 28%, and 29%, respectively. Sensitivity for polyps 1.0 cm or larger was 13% by Hemoccult and 11% by HemoQuant. In the group of relatives, estimated sensitivity for cancer at 1 to 3 years of follow-up was 25% to 33% by Hemoccult, not significantly different from the 29% to 43% by HemoQuant. CONCLUSIONS: Based on our observations in the screening setting, fecal blood appears to be a poor marker for colorectal neoplasia. Most cancers and the vast majority of polyps will be missed. Hemoccult and HemoQuant are similarly insensitive. PMID- 8437304 TI - A double-blind trial of a nicotine inhaler for smoking cessation. AB - OBJECTIVE: To evaluate the efficacy of a new nicotine inhaler system for smoking cessation. DESIGN: A 1-year, randomized, double-blind, placebo-controlled study. SETTING: Medical outpatient clinic with physicians experienced in smoking cessation assistance. SUBJECTS: A total of 286 volunteers who smoked at least 10 cigarettes daily recruited through a local newspaper. INTERVENTION: Subjects were randomly allocated to nicotine inhalers (n = 145) or placebo (n = 141) to be used for 3 months followed by tapering for 3 months in the context of minimal levels of advice and support. MAIN OUTCOME MEASURE: Continuous smoking abstinence at weeks 6, 12, 24, and 52, verified by measurements of carbon monoxide in expired air. RESULTS: Continuous smoking abstinence was significantly higher for the active nicotine inhaler group compared with the placebo inhaler group. The respective success rates were 28% and 12% after 6 weeks, 21% and 9% after 12 weeks, 17% and 8% after 6 months, and 15% and 5% after 1 year (P = .02 to .001). The mean nicotine substitution based on cotinine determinations after 2 weeks was 43% (SD, 45%) of smoking levels. The treatment was well tolerated, and no serious adverse events were reported. CONCLUSIONS: In this setting the nicotine inhaler appeared safe to use and increased success rates of smoking cessation attempts. PMID- 8437305 TI - Projections of hypertension-related renal disease in middle-aged residents of the United States. AB - OBJECTIVE: To establish nationwide projections for hypertension-related renal disease among middle-aged residents of the United States and compare disease burden in demographic subgroups. DESIGN: Integrated analysis of data from the US Census, the National Health and Nutrition Examination Survey of 1976 through 1980 (NHANES II), the 1971 through 1975 NHANES I Epidemiologic Follow-up Study, the Hypertension Detection and Follow-up Program trial, and the US Renal Data System. POPULATION: African-American and white residents of the United States, aged 30 to 69 years. MAIN OUTCOME MEASURES: Incidence rates and counts of hypertension, hypertension-related hypercreatinemia, and hypertension-related end-stage renal disease (ESRD). RESULTS: Each year, approximately 1.8 million middle-aged Americans develop hypertension, 140,000 develop hypertension-related hypercreatinemia, and 5300 develop hypertension-related ESRD. African Americans are at increased risk for hypertension (relative risk [RR], 1.6; population attributable risk [PAR], 5%), hypercreatinemia if hypertensive (RR, 2.4; PAR, 18%), ESRD if hypertensive with hypercreatinemia (RR, 2.7; PAR, 32%), and hypertension-related ESRD overall (RR, 8.0; PAR, 44%). Compared with women, men are at increased risk for hypertension (RR, 1.3; PAR, 13%) and hypertension related ESRD (RR, 1.6; PAR, 23%). Most cases of hypercreatinemia in hypertensives (73%) occur among those with mild hypertension. CONCLUSIONS: Progression to ESRD is rare in persons with hypertension-related renal disease, and factors other than blood pressure probably play an important role. A large proportion of hypertension-related renal disease cases occur among population subgroups considered to be at low risk. Interventions that favorably influence factors associated with the progression of hypertension-related renal disease in African Americans, in men, and in persons with mild hypertension, hold the greatest potential for reducing the population burden of hypertension-related ESRD. PMID- 8437306 TI - Sigmoidoscopic screening in the 1990s. PMID- 8437307 TI - Physicians and family caregivers. A model for partnership. Council on Scientific Affairs, American Medical Association. AB - Primary care physicians need a strong and effective model to guide their relationships with family caregivers, key resources for the frail elderly. Caregivers provide a significant proportion of the home care needed by the rapidly growing number of frail elderly living in the community. Caregiving exacts a physical, psychological, social, and emotional toll that no intervention strategies have proven powerful enough to offset. An effective relationship model would acknowledge the key linkage role of the primary care physician, recognize that caregivers and patients form interdependent units, and affirm a care partnership between the physician and caregiver. In this model, the physician conducts periodic assessments of the caregiver as well as the patient; uses a comprehensive home-based approach to care and services; provides training to caregivers, particularly in managing difficult behavior; validates the role of caregiver; and acts as case manager. Educational opportunities and reimbursement structures should be modified to encourage physicians to use the partnership model. PMID- 8437308 TI - Access to prenatal care following major Medicaid eligibility expansions. AB - OBJECTIVE: To determine whether lack of financial access was a significant barrier to prenatal care following major expansions of Medicaid eligibility in California. DESIGN: Retrospective analysis of birth certificates, assessing risks of inadequate prenatal care by insurance, controlling for maternal race/ethnicity, birthplace, age, parity, education, and marital status. SAMPLE: Singleton live births to California residents occurring in-state in 1990 (N = 593,510). OUTCOME MEASURES: Untimely initiation of care, two few visits, and no prenatal care. RESULTS: Despite major Medicaid expansions, nearly 11% of live births were uninsured for prenatal care. Being uninsured and having Medi-Cal were both risk factors of sizable magnitude, controlling for maternal characteristics. Compared with women who had private fee-for-service coverage, uninsured women were at elevated risk of untimely initiation (odds ratio [OR], 2.54; 95% confidence interval [CI], 2.47 to 2.60) and too few visits (OR, 2.49; 95% CI, 2.44 to 2.55). Women with Medi-Cal had a high risk of untimely care (OR, 3.33; 95% CI, 3.26 to 3.40); their risk of too few visits was also elevated (OR, 1.63; 95% CI, 1.60 to 1.66) but less than for the uninsured. Lack of private insurance was a strong risk factor for no care (OR, 6.70; 95% CI, 6.00 to 7.47). CONCLUSIONS: In spite of major Medicaid expansions, access to prenatal care was limited for women without private insurance. Medicaid was associated with untimely entry but with improved continuity. The findings suggest that financial barriers were salient even when controlling for many factors related to care seeking behavior. Policy initiatives need to address continuing financial barriers along with other obstacles. PMID- 8437309 TI - How effective are treatments for diabetic retinopathy? PMID- 8437310 TI - Folic acid-preventable spina bifida and anencephaly. PMID- 8437311 TI - How should we screen for colorectal cancer? PMID- 8437312 TI - Fracture risk in woman with osteoporosis: must tennis cease? PMID- 8437313 TI - Anticoagulation for embolic stroke. PMID- 8437314 TI - Health risks of creosotes. PMID- 8437315 TI - The challenge of blood glucose management in diabetic patients receiving enteral or parenteral nutrition. PMID- 8437316 TI - Percutaneous retrieval of embolized intravascular catheter fragment. PMID- 8437317 TI - Evaluation of a practical technique for determining insulin requirements in diabetic patients receiving total parenteral nutrition. AB - A practical technique to provide central parenteral nutrition to insulin-taking diabetic patients based on prehospitalization insulin requirements and insulin placed in the central parenteral nutrition was originally presented based on retrospective review. The present article confirms the safety and applicability of this method after a multiyear period of application. Particularly noteworthy are the absence of hypoglycemic episodes, the attainment of reasonable blood glucose control, and the relatively consistent relationship of insulin required in central parenteral nutrition to prehospitalization insulin requirements. PMID- 8437318 TI - Does portal nutrition benefit liver protein synthesis? AB - There are only a few experimental investigations on the feasibility and potential advantages of intraportal nutrition in animals and only two uncontrolled studies in humans. The purpose of this study was to compare some metabolic variables in patients who received portal or systemic nutrition after elective surgery for colorectal cancer. Twenty patients were randomized to receive postoperatively for a week a hypocaloric, "protein sparing" standard infusion via the portal (catheter in the gastroepiploic vein) (10 patients) or systemic (10 patients) route. We evaluated the basal concentrations of some visceral and acute-phase proteins and their variations in the first postoperative week and the nitrogen balance. Statistical analysis was performed by the two-tailed Student t test. There was no difference in the daily changes of the visceral and acute-phase proteins after surgery in the two groups of patients, but in the portal group there was a significantly better recovery of the level of total protein, albumin, and cholinesterase at the end of the portal infusion vs the systemic group (p < or = .005, .03, and .02, respectively). In regard to the nitrogen balance, although there was no difference in the overall balance between portal and systemic nutrition, if we separate the acute phase of the injury from the later one we do not see any significant difference in the first period but we do see a highly significant advantage for the portal group during the last 2 days (p < or = .0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437319 TI - Early parenteral nutrition in patients unconscious because of acute drug poisoning. AB - The author studied the clinical and laboratory effects of early parenteral nutrition (EPN) in patients who were comatose as a result of acute drug poisoning. All patients were unconscious at the time of admission and entry into the study and received our usual conservative therapy for the first 24 hours. Alternate patients received an EPN solution containing amino acids and glucose. Volume, composition, and caloric content of the EPN solution were calculated separately for each patient according to weight and height nomograms. It was found that the group receiving EPN (n = 46) normalized their nitrogen balance sooner and demonstrated a consistent decrease in their creatine phosphokinase level. Serum amino acid values in patients treated with EPN did not change significantly during the treatment trial. The control group (n = 40) demonstrated a significantly lower serum amino acid concentration on the third day of treatment (p < .001), had significantly more pneumonias (p < .05), and their hospitalization time was significantly longer (.01 < p < .05) than the EPN group. There were significantly fewer instances of disseminated intravascular coagulation in the group receiving EPN (p < .05). PMID- 8437320 TI - Total energy expenditure in patients with Crohn's disease: measurement by the combined body scan technique. AB - A combined body scan technique for measuring total energy expenditure (TEE) from energy intake and changes in energy stores is presented. The TEE of 13 patients with Crohn's disease who required nutrition support over a 14-day period was measured. They had a mean TEE of 33 kcal/kg per day. The components of the TEE in these 13 patients were also measured. Seventy percent of the TEE was made up by resting metabolic expenditure, 10% by diet-induced thermogenesis, and the remaining 20% by activity energy expenditure. These patients had a mean activity energy expenditure of 369 kcal/day. The diet-induced thermogenesis was a mean 12.6% increase on the resting metabolic expenditure. Each percent increase was caused by a mean of 210 kcal of energy in either the intravenous nutrition or the enteral nutrition. There was no difference in diet-induced thermogenesis between those having enteral nutrition and those receiving intravenous nutrition. Decreased activity was significantly correlated with increased activity of the disease (r = .7, p < .01). This confirms the belief that patients with Crohn's disease require no more energy (ie, 33 kcal/kg per day) than other patients. If the resting metabolic expenditure is increased through illness, then the activity energy expenditure decreases. The combined in vivo neutron activation-dual energy x-ray absorptiometry technique has allowed for the first time measurements in ward patients with Crohn's disease. The measurements confirm that TEE is not raised and that 30 to 35 kcal/kg per day is sufficient to achieve energy balance in such patients. PMID- 8437321 TI - Changes in plasma and erythrocyte fatty acids in patients fed enteral formulas containing different fats. AB - Critically ill hospital patients were fed enteral formulas containing different fat substrates. Seven patients received formula X, which contained 28 g of structured triglycerides and menhaden oil to provide 7.6 g of medium-chain fatty acids, 2.5 g linoleic acid, 1.3 g eicosapentaenoic acid, and 0.4 g docosahexaenoic acid per 1000 mL of formula. Six patients received formula Y consisting of 36.8 g of medium-chain triglycerides and corn and soy oils providing 14.3 g medium-chain fatty acids and 11.7 g linoleic acid per 1000 mL. Feeding of formula X increased plasma total phospholipid levels of eicosapentaenoic acid on days 7 and 14 and docosahexaenoic acid levels on day 14. Plasma levels of linoleic acid were reduced in formula-X-fed in comparison to formula-Y-fed patients, whereas arachidonic acid was maintained in both groups during feeding. As a result of these changes, the patients receiving formula X had decreased ratios of arachidonic acid:eicosapentaenoic acid in plasma. Formula Y feeding did not alter eicosapentaenoic acid and docosahexaenoic acid levels in the plasma. In the erythrocyte, formula X feeding resulted in a threefold increase in eicosapentaenoic acid from mean baseline levels of 0.4 +/- 0.4% to a mean value of 1.2 +/- 0.9% at day 7. The formula X feeding decreased linoleic acid levels on days 7 and 14, whereas levels of arachidonic acid and docosahexaenoic acid remained constant. Formula Y feeding did not affect any of the parameters measured for erythrocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437322 TI - Prevalence of malnutrition in alcoholic and nonalcoholic medical inpatients: a comparative anthropometric study. AB - Available data on the nutritional status of alcoholics is controversial. The present study was conducted to assess the frequency of malnutrition in alcoholic inpatients. The objectives were to (1) compare anthropometric data of hospitalized alcoholic and nonalcoholic patients and (2) evaluate the association between alcoholism and protein-energy malnutrition. It was a cross-sectional comparative study including a stratified analysis to control for potential confounding factors. Alcoholics were identified as patients with a score from the Michigan Alcoholism Screening Test > or = 8 among patients admitted consecutively to the general wards of a department of internal medicine; they were matched for sex, age, and time of admission with nonalcoholic patients (Michigan Alcoholism Screening Test score < or = 4). Nutritional status was assessed using weight, height, midarm circumference, and tricipital skinfold thickness values, which were then used to determine the Quetelet body mass index and the mid-arm muscle circumference. The study took place in general wards of internal medicine in a 1000-bed city and teaching hospital in Lausanne, Switzerland. The participants were 93 alcoholic patients and 93 controls aged 20 to 75 years, admitted from September 1, 1988, to March 18, 1989. Alcoholics were characterized by a low rate of severe protein-energy malnutrition (< 5%); their average body weight was normal, similar to the weight of nonalcoholic inpatients, and not greatly influenced by the presence or severity of concomitant liver disease. However, tricipital skinfold thickness was lower in alcoholics than in nonalcoholics (8 mm vs 10 mm, p < .05, and 13 mm vs 20 mm, p < .01, in men and women, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437323 TI - Effect of glutamine-supplemented intravenous nutrition on survival after Escherichia coli-induced peritonitis. AB - Current solution formulations for total parenteral nutrition (TPN) do not contain glutamine (GLN). The purpose of this study was to examine whether GLN supplementation of TPN would improve survival in experimental Escherichia coli peritonitis in Fischer 344 rats (190-210 g). Initial experiments were performed to determine the degree of stress and to evaluate survival after intraperitoneal E coli injection. The E coli colony used was isolated from a culture of human blood. Graded doses were injected intraperitoneally in Fischer 344 rats (190-210 g). The response of white blood cell count, plasma insulin, glucagon, and corticosterone levels, and urinary excretion of vanillylmandelic acid reflected a significant stress response for at least 3 days. Survival was dose-dependent, with 60% mortality at 3 days after injection of 5 x 10(5) colony forming units of E coli/200 g body weight. To determine whether GLN supplementation of TPN would alter survival in this E coli peritonitis model, Fischer 344 rats were randomized to receive TPN containing 4.25% standard amino acids (group STD, n = 38) or the same solution with 1.5% of the amino acid content replaced with L-GLN (group GLN, n = 38). After 7 days of TPN, 5 x 10(5) colony forming units of E coli/200 g body weight were injected intraperitoneally under direct vision through a small laparotomy. Survival was monitored for 3 days. Surviving rats were killed to determine various nutritional parameters including plasma albumin and GLN concentration, the weight and nitrogen content of the gastrocnemius muscle, and biochemical and histological composition of the small intestine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437325 TI - Stability of fat-soluble vitamins A (retinol palmitate), E (tocopherol acetate), and K1 (phylloquinone) in total parenteral nutrition at home. AB - Our purpose was to extend previous studies of the stability of vitamins A (retinol palmitate), E (tocopherol acetate), and K1 (phylloquinone) to total parenteral nutrition at-home (TPNH) admixtures. First, stability over 20 days was tested. Experimental conditions included presence or absence of lipids, presence or absence of trace elements, and storage in a glass bottle or in a single or multi-layer plastic bag (ethylene vinyl acetate, polyvinyl chloride, Stedim 5, and Stedim 6). The 20-day storage studies were conducted at 4 degrees C or at ambient air temperature. The second part of the study consisted of exposing to natural light TPNH admixtures with or without lipids, but with trace elements, in the same containers (except polyvinyl chloride). Finally, a clinical situation of TPNH was simulated with a TPNH admixture prepared 11 days before the test in a Stedim 6 plastic bag and stored at 4 degrees C in total darkness. For vitamins A, E, and K1, we observed good stability for 20 days; the final concentrations ranged from 75% to 100% of initial concentrations whatever the conditions studied. It appears that there is no significant difference of action between all containers and that the presence or absence of lipids and trace elements in admixtures stored at 4 degrees C or ambient temperature makes no difference. With exposure to sunlight, vitamin losses were 100% at 3 hours for vitamin A and 50% for vitamin K1; vitamin E concentrations were unchanged after 12 hours of experiment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437324 TI - Glutamine enhancement of structure and function in transplanted small intestine in the rat. AB - Total parenteral nutrition is required by all patients in need of small bowel transplantation. Untoward side effects of total parenteral nutrition include atrophy and hypofunction of the small intestine. Glutamine, the preferred fuel for the enterocyte, is presumably present in insufficient amounts in diets given to patients with intestinal dysfunction. In a rat model of total parenteral nutrition and small bowel transplantation, this study investigated the following: (1) whether glutamine improves graft structure and function, (2) the optimal route of glutamine delivery (intravenous vs direct infusion into the graft), and (3) the effect of glutamine on ultrastructure of the graft enterocyte. Lewis rats underwent small bowel transplantation as a Thiry-Vella graft and received total parenteral nutrition for 14 days while assigned to one of four infusion groups: 2% intravenous glutamine; 2% intravenous isonitrogenous mixture, nonessential amino acids (control); 2% glutamine into the graft; or 2% nonessential amino acids into the graft (control). Graft mucosal villous height, villous surface area, crypt depth, weight, protein, deoxyribonucleic acid content, glucose absorption, and enterocyte ultrastructure were then evaluated. Infusion of glutamine directly into the graft significantly increased mucosal villous height (p = .045), surface area (p = .029), and glucose absorption (p = .004) when compared with controls. Intravenous glutamine infusion significantly increased mucosal villous height (p = .002), surface area (p = .001), weight (p = .005), and glucose absorption (p = .04) when compared with controls. Most enterotrophic and functional benefits of glutamine were not significantly different between intravenous infusions and direct administration into the graft.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437326 TI - A prospective randomized trial comparing the silver-impregnated collagen cuff with the bedside tunneled subclavian catheter. AB - A prospective study was undertaken to compare the silver-impregnated collagen cuff (Vitacuff) with the bedside tunneled catheter. Fifty patients were randomly assigned to three groups: group I received triple-lumen catheters with Vitacuff application and a semiocclusive dressing material; group II received triple-lumen tunneled catheters with a semiocclusive dressing; and group III received triple lumen tunneled catheters with collodion as a dressing material. In patients suspected of having central venous catheter sepsis, blood cultures were obtained through the catheter, the catheter was removed, and the tip was cultured semiquantitatively. Central venous catheter sepsis was defined as a positive catheter-tip culture and blood culture for the same organism. No catheter-related sepsis was seen in either the Vitacuff or the tunneled catheters with collodion dressing. In the tunneled catheters with semiocclusive dressing, there was one case of catheter-related sepsis and one case of insertion-site infection. There was also one insertion-site infection in the Vitacuff group, but there was no statistical difference in infection rates between the three groups. PMID- 8437327 TI - Glucose response to abrupt initiation and discontinuation of total parenteral nutrition. AB - Plasma glucose was studied during the initiation of total parenteral nutrition (TPN) and the discontinuation of TPN without a tapering schedule. Blood was sampled every 5 minutes for 2 hours after the start of TPN and 1 week later as TPN was discontinued. A total of 14 initiations and 14 discontinuations were studied in 18 patients. Severity of illness in patients ranged from stable condition postoperatively to multiple-system failure; six patients had diabetes mellitus. The TPN solution was a 3:1 admixture that provided a caloric intake equal to 1.2 times the resting energy expenditure, with 40% fat and 60% carbohydrate calories. An average of 1963 kcal was provided per day (340 g of glucose, 79 g of fat). During the initiation phase, the mean increase in plasma glucose was 60 mg/dL. The increase for diabetic patients was 79 +/- 14 mg/dL compared with 52 +/- 23 mg/dL for the nondiabetics. During the discontinuation phase, the mean plasma glucose decreased 40 +/- 20 mg/dL; two patients with high concentrations of regular insulin (50 and 100 units) showed an increase in plasma glucose when the TPN was stopped. Plasma glucose returned to the preinfusion baseline after discontinuation. During both initiation and discontinuation, plasma glucose showed little change after the first 60 minutes. No clinical symptoms of hypoglycemia were observed. In conclusion, TPN as a 3:1 admixture can be safely started as full nutrition support and stopped abruptly without a tapering schedule. Plasma glucose response is rapid, predictable, and mostly complete within 60 minutes. PMID- 8437328 TI - Urinary nitrogen constituents in the postsurgical preterm neonate receiving parenteral nutrition. AB - Minimal information is available defining urinary nitrogen constituents in preterm neonates receiving parenteral nutrition (PN). The study objective was to evaluate 24-hour urine collections for total urinary nitrogen (TUN), urinary urea nitrogen (UUN), and the nitrogen content in creatinine, ammonia, free amino acids, protein, hippuric acid, and uric acid at baseline (days 1 to 2 of PN and days 1 to 3 after surgery) and 7 days later in eight preterm, postsurgical neonates. Calculation of undetermined nitrogen was also completed. Comparisons with historic, normal data were made for each urinary nitrogen constituent. At baseline, PN provided 59 +/- 10 nonprotein kcal/kg.day-1 and 430 +/- 54 mg/kg.day 1. At day 7, PN provided 106 +/- 23 nonprotein kcal/kg.day-1 and 432 +/- 30 mg/kg.day-1. TUN, UUN, and protein nitrogen decreased significantly from baseline at day 7 (p < .05). The percentages of TUN as amino acids, creatinine, and uric acid nitrogen were calculated. Percent amino acid nitrogen (6.0 +/- 2.3% vs 8.4 +/- 1.5%, p < .05), percent creatinine nitrogen (1.6 +/- 0.5% vs 2.9 +/- 0.8%, p < .001) and percent uric acid nitrogen (1.7 +/- 0.9% vs 3.6 +/- 2.1%, p < .05) increased significantly at day 7. The observed urinary free amino acid nitrogen fraction represented a higher percentage of TUN both at baseline and at day 7 when compared with term neonatal reference data, whereas creatinine nitrogen, uric acid nitrogen, and protein nitrogen represented a lower percentage of TUN. However, amino acid and creatinine nitrogen as a percentage of TUN were similar to levels in milk formula-fed preterm infants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437329 TI - Dynamic change of reticuloendothelial system function after surgical stress. AB - The influence of surgical stress on the function of the reticuloendothelial system (RES) is not well elucidated. Because we established an in vivo functional test for the RES by using chondroitin sulfate iron colloid in rabbits, the normal range of RES function in healthy volunteers (n = 12) and the dynamic change of RES function in surgical patients after distal gastrectomy (n = 14) were examined by this method. In healthy volunteers, the maximum phagocytic velocity and membrane-particle constant were 0.0310 +/- 0.0052 mg/kg per minute and 0.575 +/- 0.205 mg/kg, respectively. In surgical patients, maximum phagocytic velocity (postoperative day 1, 0.0408 +/- 0.0088; postoperative day 3, 0.0486 +/- 0.0115; and postoperative day 7, 0.0430 +/- 0.0115 mg/kg per minute) and membrane particle constant (postoperative day 3, 0.717 +/- 0.169 mg/kg) significantly increased postoperatively in comparison with preoperative values. These results indicate that the total capacity of the RES is augmented but that its functional phagocytic efficiency is diminished after abdominal surgery. This phenomenon is considered to be one of the immunological alterations caused by surgical stress. The chondroitin sulfate iron colloid test can be applied to monitor the dynamic change of the RES function under various conditions. PMID- 8437330 TI - Influence of glucose infusion on levels of phosphomonoesters and adenosine triphosphate as detected by magnetic resonance spectroscopy in a new model of core-cooling of the rat liver in situ. AB - This preliminary study was undertaken to ascertain whether our newly developed model of the cold ischemic rat liver in situ is applicable to studies designed to assess the metabolism of nutrients. Ischemia of the whole liver of 12 Wistar rats was induced by clamping all supply and drainage vessels. The ischemic liver was perfused in situ. The duration of ischemia of the liver was 20 minutes. Saline was infused into six rats throughout the experiment (group A). An intravenous infusion of glucose at a rate of 0.75 g/h per rat was begun immediately after the induction of blood-reflow to the liver (group B, n = 6). Six rats (group C) did not undergo the procedure for induction of hepatic ischemia and received glucose at the same rate as rats in group B. Changes in hepatic levels of sugar phosphates (phosphomonoesters [PMEs]), inorganic phosphorus, and beta-positioned phosphorus in adenosine triphosphate (beta-ATP) were monitored by 31P magnetic resonance spectroscopy. Ischemia caused a significant increase in levels of PMEs and a decrease in levels of beta-ATP. The infusion of glucose caused a further increase in levels of PMEs and a further decrease in levels of beta-ATP in group B. In contrast, in group C such infusion did not induce any changes in levels of PMEs or beta-ATP. In group A, PMEs and beta-ATP returned to basal levels 5 hours after the induction of blood-reflow to the liver. The changes in levels of PMEs were similar to those in levels of inorganic phosphorus in all groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437331 TI - Is fetal enteral nutrition important for normal gastrointestinal growth?: a discussion. AB - Long-term total parenteral nutrition results in atrophy of small intestinal structure and function. Maintenance or re-establishment of enteral nutrition can prevent or redress this loss. Paradoxically, the fetus develops in a total parenteral nutrition environment, but at the same time must achieve appropriate levels of gastrointestinal maturation in readiness for enteral feeding soon after birth. The fetus swallows large amounts of fluid during life in utero and growth is arrested if fetal ingestion is impaired. It is possible therefore that enteral nutrition provided by fetal swallowing is just as important in ensuring normal gastrointestinal homeostasis and growth in the fetus as it is in the adult. PMID- 8437332 TI - Complication of parenteral nutrition composed of essential amino acids and histidine in adults with renal failure. AB - This is a case report on six patients with hyperammonemia that developed while they were receiving total parenteral nutrition (TPN) as a component of renal failure therapy. Clinically, the hyperammonemia presented as mental status changes in all six cases. Four of the six patients with renal failure initially received 400 mL Amiyu in 1400 mL 17% glucose (total = 1800 mL TPN-A) administered over each 24-hour period. Two patients had been placed on 400 mL complete amino acid in 1400 mL 17% glucose (total = 1800 mL TPN-C over each 24-hour period) prior to therapy with TPN-A. Approximately 3 weeks after initiation of TPN therapy with TPN-A, episodes of mental status changes of increasing duration and paroxysms were documented in five of the six patients. In one of the patients receiving TPN-C prior to TPN-A therapy, toxicity was clinically evident only 4 days after initiation of TPN-A. Serum ammonia levels were obtained and found to be elevated in the acute (ie, presenting) stage in all patients. With the discontinuance of TPN-A, ammonia levels normalized uniformly. Mental status also improved in all cases except for the patient with rapid clinical presentation who died 2 weeks after first evidence of clinical toxicity. In cases 1, 2, and 6, serum amino acid analysis in the acute phase showed reduced levels of ornithine and citrulline, the substrate and product, respectively, of condensation with carbamyl phosphate at its entry into the urea cycle. Moreover, levels of arginine, precursor to ornithine, were found to be elevated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437334 TI - The effect of continuous enteral nutrition on gastric acidity in humans. PMID- 8437333 TI - Intermittent back pain after central venous catheter placement. AB - We report a case of inadvertent azygos placement of a central venous catheter. The patient experienced ill-defined back pain associated with total parenteral nutrition infusion. The catheter malposition remained unrecognized and resulted in extensive diagnostic work-up. Symptoms resolved after the catheter was withdrawn. PMID- 8437335 TI - Resting energy expenditure in patients with thermal injuries. PMID- 8437336 TI - Upregulation of nutrient transport in fetal rabbit intestine by transamniotic substrate administration. PMID- 8437337 TI - The discovery of the cardiac conduction system: the testimony of the authors. PMID- 8437338 TI - The influence of severe bone loss on mitral annular calcification in postmenopausal osteoporosis of elderly Japanese women. AB - We assessed the influence of aging bone calcium metabolism on mitral annular calcification (MAC) and aortic valve calcification (AVC) in 239 septua- and octogenarians (62 men, 177 women; 80.2 +/- 4.4 years). Osteoporosis was diagnosed by vertebral bone fracture. Both MAC and AVC were derived by 2-dimensional echocardiography. Bone mineral content (BMC) of the lumbar vertebral body was obtained by single-energy quantitative computed tomography using a calibration phantom. Serum calcium, phosphorus, parathyroid hormone, calcitonin, and osteocalcin were examined. Patients were classified into 3 age-matched groups in each sex: Group-C included patients with MAC (-) and AVC (-) (n = 96); Group-A was those with AVC (+) and MAC (-) (n = 80); Group-M consisted of those with MAC (+) and AVC (-) or AVC (+) (n = 63). Osteoporosis-frequency and BMC in women were significantly higher (p < 0.01) and lower (p < 0.001) respectively than those in men. Among men, osteoporosis-frequency and BMC showed no difference between the 3 groups. Among women, osteoporosis-frequency (52%) and BMC (32 +/- 23 mg/cm3) in Group-M were higher (NS) and significantly less (p < 0.01) than those (37%, 49 +/ 36) in Group-C, respectively. In both sexes, serum examinations revealed no differences between the 3 groups. These results suggest that: 1) MAC in elderly women can be attributed to ectopic calcium deposits, related to the severe bone loss caused by postmenopausal osteoporosis; 2) there is no significant relationship between the incidence of MAC or AVC and the humoral factors of calcium metabolism; and 3) AVC may be mainly caused by pressure or stress loading. PMID- 8437339 TI - Implications of delayed image on simultaneous thallium-201/technetium-99m pyrophosphate dual emission computed tomography early after acute myocardial infarction. AB - This study aimed investigate whether thallium-201 and technetium-99m pyrophosphate dual rest-redistribution emission computed tomography early after intracoronary thrombolysis may provide supplementary information for the management of patients with acute myocardial infarction. Fifty patients who received intracoronary thrombolysis underwent simultaneous dual emission computed tomography 3 days after first acute myocardial infarction. All patients who had a technetium-99m pyrophosphate accumulation were selected. Thallium-201/technetium 99m pyrophosphate overlap in the initial and delayed images early after intracoronary thrombolysis identified successful recanalization with sensitivities of 68% and 90% (p < 0.05), specificities of 47% 79% (p < 0.05), positive predictive accuracies of 68% and 88%, negative predictive accuracies of 47% and 80% (p < 0.05), and overall accuracy of 60% and 86% (p < 0.01), respectively. The patients were divided into 3 groups according to the change in thallium-201 uptake from the initial image to the delayed image on dual emission computed tomography: 20 patients had no change in thallium-201 uptake (fixed type), 16 had increases in thallium-201 uptake (redistribution type), and 14 had decreases in thallium-201 uptake (reverse redistribution type). The number of patients with successful recanalization was significantly higher in the redistribution type than in the other types (redistribution type vs reverse redistribution type or fixed type; p < 0.01, respectively). In the redistribution type a frequency of reinfarction in the same infarcted area during the hospital course was significantly higher than in the other types (redistribution type vs reverse redistribution type or fixed type; p < 0.05, respectively), which was mainly due to the patients having high grade residual stenosis. Thus, a thallium 201/technetium-99m pyrophosphate overlap in the delayed image early after acute myocardial infarction can be used as an index for predicting successful early recanalization and probably viable myocardium. In addition, the redistribution patterns on thallium-201 emission computed tomography early after intracoronary thrombolysis can be helpful in identifying patients with successful early recanalization and a high risk subset. PMID- 8437340 TI - Immunological aspects in patients with acute myocardial infarction. AB - In order to elucidate the immunological aspects of acute myocardial infarction (AMI), we studied lymphocyte subpopulations, immunoglobulin levels, and natural killer (NK) cell activity in 21 patients serially after admission within 24 h of AMI onset. The percent T cells, T cell count, and percent CD4-positive cells were significantly decreased on the 1st hospital day, compared to days 7 and 28. The CD4/CD8 ratio on the 1st day was also significantly lower than on day 7, and was significantly lower than that of normal subjects. Natural killer (NK) cell activity and serum immunoglobulin G (IgG) levels showed substantial decreases each test day, compared with those in normal subjects. However, there were no significant serial changes in the percent B cells, the B cell count, or in the serum IgG, IgA, or IgM levels. Thus, not only T cell function, but also immunoglobulin levels and NK cell activity were depressed in the acute stage of myocardial infarction. Therefore, active measures should be taken to prevent infection in the acute stage of myocardial infarction in which invasive procedures such as insertion of indwelling catheters are often necessary. PMID- 8437341 TI - Preload dependency of left atrial pump function in hypertrophic cardiomyopathy. AB - In our previous study, we reported that the left atrial contribution to left ventricular filling was decreased to a greater extent in patients with hypertrophic cardiomyopathy than in those with myocardial infarction or normal subjects during lower body negative pressure (LBNP)-induced preload reduction. To clarify the factors responsible for this difference in response, we examined changes in left atrial hemodynamic and M-mode echocardiographic indices during LBNP in patients with hypertrophic cardiomyopathy and myocardial infarction. The same degree of decrease in left atrial preload and afterload was found in both groups. Moreover, we detected no change in the left atrial fractional shortening during left atrial systole (%LAFS) in patients with hypertrophic cardiomyopathy, in contrast to a significant increase found in patients with myocardial infarction. These results showed that the greater decrease in the left atrial contribution in hypertrophic cardiomyopathy during LBNP could not result from differences in changes in left atrial preload or afterload, suggesting that it may be closely related to limitations in the compensatory augmentation of left atrial contractility. PMID- 8437342 TI - Suppression of ventricular premature contractions continues after the washout of antiarrhythmic drugs. AB - The effects of the washout of antiarrhythmic drugs on the frequency of ventricular premature contraction (VPC) were investigated in 64 patients (VPCs > 2000/day). Included were patients on mexiletine (300-600 mg/day; 23 patients), disopyramide (300-600 mg/day; 19 patients) and atenolol (50 mg/day; 22 patients). Holter monitoring was repeated before, during and after the treatment with the above 3 drugs and the efficacies of the drugs were evaluated based on the spontaneous variability before the treatment. VPC reduction exceeding the calculated spontaneous variability during drugs therapy (drug-responders) and after the washout of the drugs (wash-responders) was noted in 17 (63%) and 3 (13%) of the mexiletine group; 11 (58%) and 5 (26%) of the disopyramide group; and 13 (59%) and 8 (36%) of the atenolol group, respectively. For the entire group of 64 patients, wash-responders were noted significantly (p < 0.05) more among drug-responders (14 of 41 patients; 34%) than drug-nonresponders (2 of 23 patients; 9%). Therefore, the antiarrhythmic effects of drugs observed during drugs therapy seem to continue even after the discontinuation of antiarrhythmic drugs in 34% of patients those whose VPC reduction exceeded the spontaneous variability (drug-responders). PMID- 8437343 TI - Effects of a combination therapy of anticoagulant and vasodilator on the long term prognosis of primary pulmonary hypertension. AB - A therapy consisting of a combination of an anticoagulant and a vasodilator was investigated to determine its effects on the long-term prognosis of primary pulmonary hypertension (PPH). Twenty patients with PPH who had undergone diagnostic catheterization in our hospital were studied. The mean follow-up period after the initial catheterization was 6 years, with the longest follow-up being 24.4 years. Seven patients were treated with warfarin as an anticoagulant, combined with either isoproterenol (3 patients) or nifedipine (4 patients) as a vasodilator (AV group). The remaining 13 patients were not treated (control group). Although there were no significant differences in the physical activity or hemodynamics between the groups, improvement was seen in 43% of the AV group and in only 7.6% of the controls. The 5 year survival rate was significantly higher in the AV group (57% vs 15%; P < 0.05). Hemodynamics were evaluated repeatedly in 8 patients and improvement was seen only in the AV group. These results suggest that a therapy consisting of a combination of an anticoagulant and a vasodilator may improve the long-term prognosis of PPH. PMID- 8437344 TI - Assessment of pulmonary artery pressure by pulsed Doppler echocardiography in patients with chronic pulmonary diseases. AB - Doppler echocardiography was recently developed for obtaining a flow velocity profile at any point in the cardiac chamber. A pulsed Doppler technique combined with cross sectional echocardiography was used to examine the flow velocity pattern in the right ventricular outflow tract in 32 patients with chronic pulmonary disease (CPD) and in 15 healthy subjects as controls. All patients underwent cardiac catheterization. Pulmonary flow velocity profiles in the right ventricular outflow tract were recorded simultaneously with electrocardiograms and pre-ejection periods (PEP), right ventricular ejection time (RVET), acceleration time (AT), and calculated PEP/RVET, AT/RVET were determined. All normal subjects had "dome-like" flow velocity patterns with a peak flow at the midsystole. In patients with CPD, there was a significant correlation between log10MPAP (mean pulmonary arterial pressure) and AT/RVET, the coefficient being r = -0.623, between PVR (pulmonary vascular resistance) and AT/RVET (r = -0.52), and between SVI (stroke volume index) and PEP (r = -0.645). Complications of pulmonary hypertension in CPD were relatively mild, but the pulsed Doppler technique was found useful for evaluating pulmonary arterial pressure and other right heart hemodynamics of CPD patients. PMID- 8437345 TI - Evaluation of transient heart murmur resembling pulmonary artery stenosis in term infants by Doppler and M-mode echocardiography. AB - Four term infants with transient murmurs resembling that of pulmonary artery stenosis were examined. A grade 3/6 systolic ejection murmur was transmitted clearly to the entire precordium and the back. This murmur was first detected 7 days after birth in 1 infant and at a 1-month medical check in the other 3. The murmur continued for 7 to 22 weeks, with an average of 12 weeks. It gradually localized in the region of the left sternal border, and eventually disappeared. At the first medical examination, peak velocities of over 2.0 m/s, in the left or right pulmonary artery, were detected by a pulsed Doppler. The diameter of the right pulmonary artery was small (mean, 58 +/- 8%; range, 46 to 64% of predicted normal). When the heart murmur disappeared, the diameter of the right pulmonary artery (mean, 97 +/- 28%; range, 70 to 126%) had increased significantly (p < 0.05). Peak velocities in the right pulmonary arteries had decreased significantly (2.22 +/- 0.37 m/s vs 1.13 +/- 0.10 m/s, p < 0.01). We suggest that hypoplasia of pulmonary artery branches, in relation to the main trunk, is the main cause of the murmur resembling pulmonary artery stenosis. PMID- 8437346 TI - A case of pheochromocytoma complicated with acute renal failure and cardiomyopathy. AB - We encountered a case of pheochromocytoma which was characterized by the sudden onset of acute renal failure and pulmonary edema. Acute renal failure was rapidly improved after surgical removal of the tumor. This patient was also found to have a hypertrophied, dilated and hypokinetic left ventricle as assessed by echocardiography. Two years after tumor resection, cardiac size and function were normalized. This shows that a catecholamine-induced cardiomyopathy is reversible. PMID- 8437347 TI - [Cardiac output measurement with transtracheal Doppler in children]. AB - Cardiac output (CO) measurement with transtracheal Doppler (TTD) was compared with that measured by transthoracic electrical bioimpedance (TEB) in normal children, and with that by thermodilution (TD) in children with heart disease. In CO measurement, TTD correlated significantly with TD (r = 0.65, P < 0.05), but not with TEB. Although aortic diameters, which were necessary for CO measurement with TTD, were far from the values in Woezik's nomogram of normal children, they correlated significantly with those measured from angiographies in children with heart disease (r = 0.92, P < 0.05). However, it is assumed that the significant correlation of diameters in children with heart disease might be produced by the offset of measurement errors in position and angle of the Doppler probe. PMID- 8437348 TI - [Haemodynamic effects of vasodilators in dogs--a comparison of prostaglandin E1, nicardipine and nitroglycerin]. AB - Effects of vasodilation by prostaglandin E1 (PGE1), nicardipine (NIC) and nitroglycerin (TNG) were investigated separately in adult mongrel dogs. Mean arterial pressure was lowered and maintained at 90% and 70% of the control value. Cardiac output (CO), pulmonary arterial pressure (PAP), pulmonary capillary wedge pressure (PCWP) and right atrial pressure (RAP) were measured by a thermodilution pulmonary artery catheter and blood flow of hepatic artery (HABF), portal vein (PVBF) and mesenteric artery was measured by electromagnetic flowmetry. 1) PGE1: Heart rate (HR) and CO were unchanged and left ventricular stroke work (LVSW) decreased. HABF was unchanged, but PVBF increased significantly. 2) NIC: HR increased and systemic vascular resistance decreased significantly. Therefore, CO increased remarkably, compared with the other two drugs. Though LVSW was unchanged, right ventricular stroke work (RVSW) increased with elevation of PAP. In the hepatic circulation, HABF and PVBF decreased slightly. 3) TNG: LVSW and RVSW decreased significantly. HABF increased slightly and PVBF increased significantly. PMID- 8437349 TI - [Application of the concept of fuzzy logistic controller for treatment of hypertension during anesthesia]. AB - The concept of Zadeh's fuzzy logistic controller was applied to control hypertension during anesthesia, and its clinical usefulness was examined in patients undergoing elective surgery. Arterial blood pressure was determined by use of an automatic blood pressure device. Nicardipine was used as hypotensive drug. Based on the fuzzy control rules, we developed state-action diagram so as to maintain systolic blood pressure at around 130 mmHg. Nicardipine was infused by using a digitally controlled infusion pump, and its infusion rate was changed according to this diagram. Although acute hypertension associated with endotracheal intubation was not significantly attenuated, hypertension associated with either skin incision or endotracheal extubation, where blood pressure increased slowly, was successfully controlled with our system. These results suggest that the application of the concept of fuzzy logistic controller is useful for treatment of hypertension during anesthesia, especially when blood pressure increases slowly. PMID- 8437350 TI - [Gastrointestinal mucosal ischemia in hemorrhagic shock--measurement with a tonometer]. AB - Splanchnic ischemia produces the most rapid progression of mucosal injury. A reliable method for monitoring the adequacy of tissue oxygenation in the mucosal layer would be clinically valuable. In this study, we investigated the potential value of tonometric intestinal intramucosal pH (pHi) monitoring during hemorrhagic shock in twelve anesthetized dogs. The tonometer consists of a sampling tube with a silicone balloon attached to the tip that is freely permeable to CO2. Intestinal pHi was calculated by the Henderson-Hasselbalch equation and measurements of the PCO2 of the normal saline within the balloon and arterial bicarbonate. The tonometer was placed in the midpart of the small intestine through a small enterotomy. Arterial blood was removed into a heparinized bag to achieve a mean arterial blood pressure of 50-60 mmHg for two hours. Baseline pHi level was 7.28 +/- 0.02 (mean +/- SE). Following hemorrhage, pHi continued to decrease significantly during the experiments down to 6.94 +/- 0.05 at one hour and 6.82 +/- 0.12 at two hours. By treatment with an intravenous infusion of dopamine at a rate of 3 micrograms.kg-1.min-1 started at one hour after hemorrhage, pHi did not returned to baseline levels. Monitoring pHi in the small intestine using tonometer could be a useful technique to provide early detection of insufficient mucosal blood flow. PMID- 8437351 TI - [Evaluation of the peripheral circulation during surgery by the difference between the central and peripheral temperature]. AB - The peripheral circulation during surgery was evaluated by the difference between rectal and sole deep temperature (RT-SDT) in 160 patients. Moreover it was investigated whether the peripheral circulation is influenced by the operation site, the method of anesthesia, the age of patient, the volume of infusion and blood loss. In many patients during intracranial, thoracic and upper abdominal surgeries, RT-SDT dissociated with time. But the change of RT-SDT varied with the anesthetic method. During upper abdominal surgery, RT-SDT tended to dissociate wtih the halothane (H) or enflurane (E)+N2O anesthesia and the wide dissociation was observed with fentanyl+droperidol+N2O anesthesia (NLA) on and after the 4th hour during the surgery. In contrast, RT-SDT continued to converge throughout the surgery in H or E+N2O+epidural anesthesia. The influence on RT-SDT of age, volume of infusion and blood loss, varied with the anesthetic method also. RT-SDT on the 4th hour during surgery correlated with the age of the patient, the volume of infusion in the H+N2O anesthesia, and with the volume of blood loss under NLA. The peripheral circulation during the surgery is affected seriously by anesthesia and the site as well as time of the operation. Therefore the anesthetic method should be selected in consideration of the type, length and site of operation. Some counter-measures should be taken in order to maintain good peripheral circulation in long operations. PMID- 8437352 TI - [Effects of prostaglandin E1 on renal function during deliberate hypotension with epidural anesthesia]. AB - We studied the effects of prostaglandin E1 (PGE1) on renal function during and after deliberate hypotension induced by epidural anesthesia. Twenty-seven ASA class 1 patients undergoing rotatory acetabular osteotomy were divided into three groups according to the dose of PGE1. Deliberate hypotension was induced and maintained during the surgery by epidural anesthesia combined with general anesthesia. PGE1 increased urine output and creatinine clearance (Ccr) during hypotension in dose dependent manner, and the changes were statistically significant compared with control at the dose of 0.02 micrograms.kg-1 x min-1 (gamma). PGE1 also tended to increase postoperative urine output and Ccr. Regardless of PGE1 administration, urine NAG/Cr ratio tended to increase during and after deliberate hypotension. Though total dose of local anesthetics was attenuated by PGE1, serum catecholamine levels of all patients were within normal ranges. In conclusion, PGE1 0.02 gamma is effective to maintain urine output during deliberate hypotension with epidural anesthesia. However, PGE1 is unlikely to prevent renal tubular damage at the dose less than 0.02 gamma. PMID- 8437353 TI - [Clinical study of total intravenous anesthesia with droperidol, fentanyl and ketamine--effects of nicardipine, diltiazem and nifedipine on intraoperative hypertension]. AB - Effects of Ca ion channel blockers, nicardipine, diltiazem and nifedipine on intraoperative hypertension were evaluated clinically in ninety surgical patients who received various surgical procedures under total intravenous anesthesia with droperidol, fentanyl and ketamine. When the systemic blood pressure exceeded 160 mmHg systolic at least for ten minutes, even though they received a total dose of 10-15 micrograms.kg-1 of fentanyl, one of the following three antihypertension drugs was administered:nicardipine 0.5-1.0 micrograms i.v., diltiazem 5-10 mg i.v. and nifedipine 5-10 mg intranasally. The effects were evaluated by measuring the systemic blood pressure, heart rate and rate pressure product, before the administration as well as 5, 15, 20 and 30 minutes after the administration. Following the injection of the drug a significant 10-20% reduction in the mean systemic blood pressure was observed in the nifedipine group, while less decrease was observed in the diltiazem and nicardipine groups. The mean heart rate in the nifedipine group increased slightly, while a slight decreases was observed in the other two groups. Therefore the rate pressure product was reduced significantly in three groups, but there was no significant difference among them. No adverse episodes such as ischemic changes on E.K.G. and deterioration of the cardiovascular system were encountered in any patients. We conclude that any of these drugs, particularly nifedipine would be appropriate to control hypertension during total intravenous anesthesia with droperidol, fentanyl and ketamine. PMID- 8437354 TI - [Plasma levels of isosorbide dinitrate and its metabolites during intravenous infusion in surgical patients--effect of preoperative administration of isosorbide dinitrate]. AB - Nineteen patients with ischemic heart disease were studied to determine plasma levels of isosorbide dinitrate (ISDN) and its metabolites, isosorbide-2 mononitrate (2-ISMN) and isosorbide-5-mononitrate (5-ISMN) for 6 hrs during intravenous administration of ISDN, using gas chromatography. Differences in plasma levels of these substances were also evaluated in patients with or without preanesthetic medication of ISDN. These patients ranging in ages from 42 to 80 years were administered ISDN intravenously at a rate of 1 micrograms.kg-1 x min-1 during anesthesia and surgery. Preanesthetic administration of ISDN consisted of transdermal application of 40 mg dose. Surgery included gastrectomy, pneumonectomy, extended cholecystectomy, radical mastectomy and so on under either enflurane anesthesia or neuroleptanesthesia. Plasma ISDN levels increased and reached a plateau 3 hrs after the start of intravenous infusion of ISDN in patients of both groups. Plasma 2-ISMN levels increased gradually and reached a plateau 5 hrs after the commencement of intravenous administration of ISDN in patients of both groups. Plasma 5-ISMN levels increased gradually reaching the peak 6 hrs after the start of intravenous infusion of ISDN in both groups. Plasma ISDN, 2-ISMN and 5-ISMN levels were slightly higher in patients who received preanesthetic ISDN than in those who did not receive preanesthetic ISDN. However, there were no statistical differences in plasma ISDN or 2-ISMN levels between the groups except prior to the infusion. On the contrary, plasma 5-ISMN levels were significantly higher in patients who received preanesthetic ISDN than in those who did not receive preanesthetic ISDN for 3 hrs after the start of the infusion. PMID- 8437355 TI - [Predicting the difficulty of laryngoscopy using the distance between the lower border of the mandible and the thyroid notch]. AB - We examined the relationship between the degree of difficulty in visualization of the larynx and the distance from the lower border of the mandible to the thyroid notch (M-T distance). Patients were examined and the M-T distance was measured with their neck fully extended during preoperative period. Difficulty of laryngoscopy was graded as reported previously. Five hundred sixty one patients were assessed, and those with obvious neck and head pathology were excluded. There were 440 cases (78.4%) in grade 1, 116 cases (20.7%) in grade 2 and only 5 cases (0.9%) in grade 3. There were no grade 4 cases. The M-T distance was 5.4 +/ 0.6 cm in grade 1, 4.6 +/- 0.7 cm in grade 2 and 3.6 +/- 0.7 cm in grade 3. These were significantly different with each other (P < 0.05). If the M-T distance is 4.5 cm or less, the difficulty in visualization of laryngoscope increases. Therefore, in the case in which the M-T distance is 4.5 cm or less, we recommend further examination and preparation for difficult laryngoscopy. PMID- 8437356 TI - [A better method to attach an endotracheal tube to the stylet of the Bullard laryngoscope]. AB - The Bullard laryngoscope with its introducing stylet is useful in a variety of patients with airway problems, but it poses difficulties in some cases where an endotracheal tube (ETT) catches on the ary-epiglottic fold and cannot be advanced into the trachea. This difficult may be avoided by slightly angulating the tip of the ETT so that it is directed in a better alignment toward the rima glottis. The efficacy of the two methods of angulation was studied. One hundred and eight patients were randomly assigned to one of three groups. In group 1 (control, 36 patients), the ETT was attached naturally to the stylet with the bevel facing left. In group 2 (36 patients), the ETT was hooked on the distal end of the stylet at the Murphy eye, as recommended by the manufacturer. In group 3 (36 patients), the ETT was set over the stylet after being rotated 180 degrees so that the bevel was directed to the right. Intubation on the first attempt was successful in 56% of group 1, 83% in group 2 and 100% in group 3. The patients in groups 1 & 2 in whom first attempt failed were all successfully intubated on the second trial with the method used in group 3. This method (180 degrees rotation of the ETT on the stylet), is applicable to any ETT with or without the Murphy eye. PMID- 8437357 TI - [From multiple regression analysis to logistic model, proportional hazard model and log linear model. Its concept and application]. AB - Recently logistic model, proportional hazard model and log linear model have been used frequently in the medical literatures. Here, each model is reviewed briefly from basics to its application, pointing out pitfalls in its application, some of which are common to any regression analysis. The logistic model is especially useful for the analysis of retrospective data where odds ratio is utilized to evaluate the outcome probability. On the other hand, proportional hazard model is useful when we analyze censored data, utilizing hazard function. Log linear model has been used where contingency table has more than three independent variables, the situation where its applicability in clinical medicine is wide. Familiarity with these statistical methods would enable us to evaluate data more effectively and efficiently and ultimately to read literature more easily. PMID- 8437358 TI - [Clinical evaluation of Engstrom's electrically controlled ELSA for low flow closed circuit anesthesia]. AB - Many anesthesiologists are now interested in low flow, closed circuit anesthesia from an economical and environmental point of view. In order to evaluate clinically a newly developed electronically controlled anesthesia machine Engstrom's ELSA, we compared low flow, closed circuit anesthesia on 38 ASA I-II patients using ELSA, with high flow anesthesia on 12 ASA I-II patients using a conventional anesthesia machine. The results were as follows; 1. We could perform safe and economical low flow, closed circuit anesthesia using ELSA's injection vaporizer and accurate monitoring devices for O2, N2O, CO2 and concentrations of various volatile anesthetic agents. 2. Under low flow anesthesia, isoflurane consumption was 5.3 +/- 1.1 ml.h-1 x Vol.%-1 (mean +/- SE) with ELSA, which is about one fourth of the high flow anesthesia consumption (22.6 +/- 2.1 ml.h-1 x Vol.%-1 (mean +/- SE). 3. Low flow closed circuit anesthesia could maintain significantly higher temperature and humidity compared with high flow anesthesia. 4. Under low flow anesthesia of more than 7hrs, color of soda lime becomes blue, but this does not affect FIO2 nor PaCO2, and the method is clinically safe for patients. PMID- 8437359 TI - [Changes in 3 different kinds of body temperature during CPR for DOA patients]. AB - We monitored 3 different kinds of temperature (the tracheal, forehead deep and rectal) during CPR for 8 DOA patients. The forehead deep temperature rose slowly from room temperature, and gradually reached the tracheal temperature. The rectal temperature, except for 2 cases, almost immediately exhibited a temperature close to the tracheal temperature. In 2 exceptions, the rectal temperature exhibited a much lower value than the other temperature monitors. On the other hand, the tracheal temperature seemed to represent the core temperature in all cases during CPR. In conclusion, the tracheal temperature is useful for the monitoring of the patient's temperature during CPR because it represents the core temperature and endotracheal intubation is essential for CPR. PMID- 8437360 TI - [Evaluation of blood purification in perioperative acute renal failure]. AB - The technical aspects of blood purification have made a great progress during 1980's. We reviewed our experiences of blood purification for the past six years. Between 1986 to 1991, we treated 48 perioperative patients with acute renal failure (ARF). Four were intraoperative cases and 46 were postoperative cases. Three of four intraoperative patients received major cardiovascular surgery, and hemodialysis was connected directly to ECC in these three cases, and in other one case, ARF was treated with continuous hemofiltration (CHF). There was no intraoperative complication. One patient died of septic multiple organ failure (MOF), but other three patients were discharged uneventfully. Thirty five postoperative ARF patients showed oliguric ARF, and their major causes were LOS (65%) and septic shock (29%). We treated these ARF patients with CHF combined with HD (63%), CHF only (28%) and HD only (9%). There were 21 deaths (60%) in this group and most common cause of death was septic MOF. Eleven postoperative ARF patients showed non-oliguric renal failure, and major cause of this type of ARF was thought to be aortic dissection and relative hypotension (45%). We treated these non-oliguric ARF patient with HD only (73%) and HD combined with CHF (27%). One of these non-oliguric ARF patients died from ARDS. PMID- 8437361 TI - [Anaesthetic management of pediatric renal transplantation for chronic renal failure]. AB - We evaluated the preoperative and intraoperative general condition of 33 pediatric kidney recipients. Eighteen patients were anaesthetized with lumbar epidural anaesthesia. Ten patients were with nitrous oxide-oxygen-halothane, 5 cases were with NLA. Preoperatively many children had cardiovascular and metabolic complications. For example 39% of patients had history of hypertension. Sixty-seven percent of patients were found to have cardiomegaly (cardio-thoracic ratio > 50%) with chest X-ray film. Seven of 9 patients undergoing echocardiogram had abnormality of cardiac wall motion, valvular impairment, pericardial effusion. In forty-eight percent of patients, hyperlipidemia was found. During operation we could not maintain the cardiovascular stability following intratracheal intubation and manipulation of vena cava or abdominal aorta under NLA or nitrous oxide-oxygen-halothane anesthesia. Epidural analgesia inhibited the cardiovascular fluctuation following these surgical stresses. We concluded that epidural analgesia is the best anaesthesia for pediatric renal transplantation and phentolamine or PGE1 are useful to maintain cardiovascular stability and transplanted kidney function. PMID- 8437362 TI - [Caesarean section in a patient with past history of fulminant malignant hyperthermia]. AB - Caesarean section in a 26 year old patient (50 kg, normal weight 36 kg) with past history of fulminant malignant hyperthermia (f-MH) is reported. Hyperthermia over 42 degrees C and subsequent cardiac arrest occurred during general anesthesia with nitrous oxide-oxygen-halothane and succinylcholine when she had been planned to perform hip joint arthroplasty at the age of 7. Prophylactic oral dantrolene administration started 4 days before the operation and the dose went up to 75 mg. Further 25 mg was given as premedication on the day of the operation. Intravenous dantrolene was administered 1.2 mg.kg-1 during the operation and 0.6 mg.kg-1 on the day after surgery. The Caesarean section was performed under spinal anesthesia with hyperbaric tetracaine 20 mg. No clinical symptoms of MH occurred during perioperative period. The delivered baby was a healthy female and no side effects of dantrolene were observed. PMID- 8437363 TI - [Anesthesia for venoplasty of right hepatic vein and liver portion of inferior vena cava using veno-venous bypass]. AB - A patient with Budd-Chiari syndrome who underwent a new surgical technique; venoplasty of right hepatic vein and liver portion of inferior vena cava using veno-venous bypass, was reported. The patient was 31 year-old man whose weight and height were 55 kg and 157 cm, respectively. During the anesthetic management of this patient, we encountered following problems; continuous massive bleeding, profound hypothermia and hemodynamic derangement. These problems were similar to those of liver surgery using veno-venous bypass such as extracorporeal liver surgery and liver transplantation. PMID- 8437364 TI - [Right ventricular perforation and cardiac tamponade caused by a central venous catheter]. AB - A 5 year old girl with ASD was scheduled for open heart surgery. A central venous catheter was placed via the right infraclavicular vein after induction of anesthesia. Thirty minutes after insertion of the catheter, a decrease in arterial pressure and pulse pressure, an increase in heart rate and central venous pressure were observed. Cardiac tamponade was revealed by rapid opening of the chest. Gushing blood out of a hole in the right ventricular free wall was confirmed by pericardiotomy. The hemodynamics were stabilized by blood transfusion and surgical closure of the hole on the ventricle. This perforation was thought to be caused by careless insertion of a relatively stiff central venous catheter. PMID- 8437365 TI - [Coronary artery spasm under general and epidural anesthesia]. AB - A 66-year-old man without history of angina pectoris was scheduled for subtotal gastrectomy under epidural anesthesia supplemented with nitrous oxide and isoflurane. ECG showed an elevation of ST segment after hypotension. It passed into Wenckebach A-V block and complete A-V block. But an elevation of ST segment was relieved by raising blood pressure and it became sinus rhythm. Serum enzymes (CPK-MB, GOT and LDH) were normal after operation. It is suspected that coronary spasm was induced by hypotension and vagal stimulation under inadequate level of anesthesia, though we could not prove this arteriographically. PMID- 8437366 TI - [Successful anesthetic management of a patient with a giant mediastinal tumor]. AB - Because of its anatomical location, mediastinal tumor is frequently accompanied by airway stenosis and signs indicating compression of the heart and large vessels. For this reason, a patient with this tumor often requires an urgent operation. We recently conducted such an operation on a girl 2 year and 7 month old in whom a giant tumor originating from the posterior mediastinum had caused dyspnea. In this case, anesthesia was induced with ketamine. Intubation was carried out while the girl was semiawake. No muscle relaxants were used, and spontaneous ventilation was partially preserved. During the operation, anesthesia was maintained with oxygen, nitrous-oxide and halothane, without using muscle relaxants. Although intratracheal bleeding, caused by manipulation of the tumor, aggravated the blood gas data, this could be coped with by elevating the oxygen concentration in the inspired gas. During the operation, respiratory control with 10cmH2O PEEP was carried out to cope with atelectasis from lung compression by the tumor. The postoperative course was excellent. From anesthetic management of this case we emphasize the following points: (1) preoperative assessment of the relationship between posture and dyspnea and assessment of the locational relationships of the tumor, heart, vessels and trachea, using CT, ultrasonography, bronchoscopy, etc; (2) utilizing a pulse oximeter, monitoring CO2 in expired gas and monitoring CVP during operation; (3) avoidance of the use of muscle relaxants before the improvement of the symptoms arising from tumor caused compression; and (4) close respiratory care after operation. PMID- 8437367 TI - [Congenital oropharyngeal wall stenosis: a case of difficult endotracheal intubation]. AB - We experienced a case of difficult endotracheal intubation. The patient was a 43 year-old female with congenital oropharyngeal wall stenosis. She was suffering from fibromyoma of uterus and an operation was scheduled under general anesthesia. Her natural voice was nasal. She denied having any respiratory difficulty or difficulty in swallowing. Respiratory function test revealed a low peak flow but the other data were normal. Preceding endotracheal intubation, at laryngoscopy we noticed a stenosis of upper airway because of the web, extending from the middle pharynx to soft palate and its diameter was about 1 cm. Ordinary endotracheal intubation was impossible because of the stenosis. In this case, fortunately we succeeded fiberoptic endotracheal intubation under spontaneous respiration. We conclude that the examination of the pharynx is very important during the perioperative period. PMID- 8437368 TI - [Evaluation of a pressure and volume-relief instrument (modified Brandt's rediffusion system) to prevent increase in endotracheal tube cuff pressure]. AB - Nitrous oxide diffuses into the endotracheal tube cuff and then overexpand the cuff. This causes upper airway obstruction and trauma in intubated patient during general anesthesia. We evaluated the efficacy and a safety of a pressure and volume-relief instrument (modified Brandt's rediffusion system), which can easily be made by ourselves, to prevent increases in endotracheal tube cuff pressure. Fourteen intubated patients under general anesthesia with nitrous oxide and oxygen were randomly allocated into two groups: in one group (control group, n = 7), endotracheal tube cuffs were inflated by air at time of intubation; in other group (rediffusion group, n = 7), tube cuffs were inflated by air and thereafter a pressure and volume-relief instrument (modified Brandt's rediffusion system) was attached to the end of pilot balloon. Pressure of endotracheal tube cuffs was monitored and recorded until the extubation. Time interval until the pressure of tube cuffs increased more than 23 mmHg, which inhibit the local circulation on the tracheal cartilage, in rediffusion group (274.7 +/- 95.9 min) was significantly longer than the duration in control group (64.7 +/- 23.5 min). We conclude that the rediffusion instrument is effective and safe to prevent the rise in the pressure of an endotracheal tube cuff. PMID- 8437369 TI - Cytoprotective action of L-arginine against HCl-induced gastric injury in rats: involvement of nitric oxide? AB - We examined the cytoprotective effect of L-arginine on gastric damage induced by 0.6 N HCl in rats and investigated whether the mechanism of this action is related to the nitric oxide (NO)-mediated protection. The animals were given 0.6 N HCl by gavage and killed 1 hr later. L-Arginine (100, 300 and 750 mg/kg) given p.o. 30 min before HCl treatment prevented these lesions in a dose-dependent manner, but had no effect when given i.v. (200 mg/kg). Similar effects were observed by D-arginine but not by an equimolar dose of mannitol. This effect of L arginine (p.o.) was attenuated significantly by prior administration of indomethacin (5 mg/kg, s.c.) but not by NG-nitro-L-arginine methyl ester (L-NAME) (5 mg/kg, i.v.), the NO synthase inhibitor. Both L- and D-arginine produced a reduction in potential difference (PD), inhibition of gastric motility, and increases of luminal pH and mucosal blood flow when they were given intragastrically. Indomethacin significantly mitigated these changes induced by L arginine except PD reduction, while L-NAME showed significant inhibition only against the increased pH response. We conclude that L-arginine given p.o. exhibits gastric cytoprotection against HCl-induced damage in rats, probably by acting as a mild irritant. The mechanism of this action may appear through "adaptive cytoprotection" mediated by endogenous prostaglandins and does not involve the NO-mediated protective pathway. PMID- 8437370 TI - A comparison of the effects of estradiol and 2- and 4-hydroxyestradiol on uterine ornithine decarboxylase activity in immature rats. AB - Effects of estradiol (E2) and catechol-estrogens (CEs: 2-OHE2 and 4-OHE2) on uterine ornithine decarboxylase (ODC) activity have been compared in immature rats. The intensity of their actions by s.c. (1 microgram) and intrauterine right horn (i.u., 25 ng) injection was in the order of: 4-OHE2 > or = E2 > 2-OHE2. Although i.u. -injection of E2 caused an increase in ODC activity in the left (intact)-horn, which was about 60% that of the right-horn, the effects by CEs were limited only to the right-horn. The results are consistent with the previous view about the order of the potency of 4-OHE2 and 2-OHE2 and also suggest that locally produced CEs may play a role in the physiological functions of the production site. PMID- 8437372 TI - Inhibitory effects of a novel antiplatelet agent, E5510, on collagen-induced platelet-derived growth factor release and aggregation of human platelets in vitro. AB - E5510, 4-cyano-5,5-bis(4-methoxyphenyl)-4-pentenoic acid, is a new anti-platelet aggregation agent under development. We examined the inhibitory efficacy of E5510 on PDGF-release from washed human platelets. E5510 concentration-dependently inhibited collagen-induced PDGF release from human platelets. PDGF release was reduced to below the detection limit (0.47 ng/ml) by preincubation of platelets with 0.04 microM or higher concentrations of E5510. Total growth factor release from platelets was also measured by a bioassay with cultured smooth muscle cells. E5510 almost completely abolished the mitogenic effect of collagen-induced platelet releasates at concentrations of 0.04 microM or higher. Our data suggest that the release of PDGF and other growth factors was inhibited by E5510 at the same concentration that inhibited platelet aggregation. PMID- 8437371 TI - Influence of imidapril on abnormal biochemical parameters in salt-loaded stroke prone spontaneously hypertensive rats (SHRSP). AB - Many of the disorders in urinary, biochemical, and hematological parameters induced by salt-loading in stroke-prone spontaneously hypertensive rats (SHRSP) were significantly ameliorated by chronic treatment with angiotensin converting enzyme inhibitors, imidapril (1 and 2 mg/kg) and enalapril (2 mg/kg). Through the improvement of these parameters, the treatment reduced the incidence of stroke but did not suppress the development of hypertension. These results suggest that the prophylaxis of stroke in SHRSP is probably due to systemic improvement as judged from the parameters of renal functions. PMID- 8437373 TI - [Coronary artery bypass grafting with all arterial grafts using the internal thoracic, the gastroepiploic and the inferior epigastric arteries]. AB - CABG with all arterial grafts using both the internal thoracic artery (RITA, LITA), the right gastroepiploic artery (GEA) and the inferior epigastric artery (IEA) was performed in 26 patients from July 1989 to August 1991. There were no early and late deaths. Early postoperative coronary angiography in all patients revealed that the best choice of anastomosis was RITA to LAD, LITA to LCX or DIA, and GEA to RCA (type A). All arterial grafts CABG is safe and feasible, but the saphenus vein graft must be used to avoid the anastomosis from small GEA to small LCX. PMID- 8437374 TI - [Nutritional improvement after operation of valvular heart diseases with protein calorie malnutrition]. AB - We evaluated the nutritional states before and after operation in patients with severe valvular heart disease characterized by malnutrition. The patient population consisted of 6 females, age range between 42 and 60, average 52.2 years old. The valve lesions were mitral stenosis in 2, combined aortic and mitral valve diseases in additional 4 patients, and moderate to severe tricuspid regurgitation was noted in 5 of these 6 patients. All 6 patients underwent a successful mitral (c/s aortic) valve replacement, and 5 of 6 tricuspid annuloplasty. The ideal body weight increased significantly from 77.9 +/- 3.4% preoperatively to 84.6 +/- 3.9% postoperatively (p < 0.01). Late postoperative cardiac catheterization revealed an improvement of mixed oxygen saturation (61.3 +/- 3.8%, preoperatively vs 67.3 +/- 5.6%, postoperatively; p < 0.01). The postoperative serum prealbumin, retinol binding protein and K value in intravenous glucose tolerance test increased significantly (p < 0.05) compared to those before operation. In conclusion, our data suggested that corrective surgery would have a good effect on nutritional improvement of the protein-calorie malnutrition caused by valvular heart diseases. PMID- 8437375 TI - [Surgical treatment of cardiac cachexia with mitral valve disease: the effect of preoperative IVH and left atrial plication on postoperative respiratory condition]. AB - Twenty-four patients with cardiac cachexia associated with mitral valve disease were evaluated from the point of postoperative respiratory management. Our previous study suggested that preoperative intravenous hyperalimentation (IVH) had just a effect on postoperative respiratory management, but another study suggested that left atrial plication (LAP) for giant left atrium might improve the postoperative respiratory function. Therefore, four groups could be identified: (1) IVH group (17 patients), (2) No-IVH group (7 patients), (3) LAP group (6 patients), (4) No-LAP group (18 patients). The hospital mortality was 18% in IVH group and was not related to the postoperative respiratory distress. On the contrary, the mortality in No-IVH group was 57%, related to the postoperative respiratory distress. The mortality of LAP group was 67%, and was related to the respiratory distress except one patient. In No-LAP group which had undertaken preoperative IVH, the mortality was 17%. As a result, preoperative IVH therapy may consider to be a favorite procedure in order to get the good postoperative respiratory condition, but LAP itself would be suspicious for this purpose. PMID- 8437376 TI - [Safe and accurate coronary artery bypass grafting: combined use with single aortic clamp and retrograde coronary perfusion]. AB - Neurological injury following myocardial revascularization may result from embolization of atheromatous debris from clamping the diseased aorta. The hazards of manipulating and clamping the aorta has been reported in some literatures. The proximal anastomoses with partial occluding clamp is conventional technique, but it may cause neurological injury, aortic tear or traumatic laceration. We developed a technique for coronary bypass grafting with single aortic cross clamp and combined antegrade/retrograde infusion of cardioplegia. Our method allows accurate performance of the proximal anastomosis without partial clamping and adequate protection of myocardium. PMID- 8437377 TI - [Suppurative mediastinitis after open heart surgery: in comparison between infants-children and adults]. AB - Among 361 consecutive patients who underwent open surgery from Jan. 1987 to Sept. 1991, risk factors and clinical courses were analyzed retrospectively in comparison between infants-children and adults. Seven mediastinitis (4.0%) occurred in 173 adult patients (20 to 75 y/o, mean: 54.4 y/o) and were not associated with age, sex, type of disease, and duration of operation or cardiopulmonary bypass. Postoperative mediastinitis significantly increased in the patients with low output syndrome (LOS) determined as use of IABP and/or assistant circulations (p < 0.001) and reexploration for bleeding or tamponase was associated with an increased risk for mediastinitis (p < 0.01). Five mediastinitis (2.7%) occurred in 188 infants and children (0 to 17 y/o, mean: 4.2 y/o). All patients involved with mediastinitis were less than 12 month old (2.6 +/- 3.3 month). None of the other factors was associated with an increased risk for this complication. Bacterial cultures of exudate were positive in 11 of 12 patients, and identified as MRSA in 10 and Staphylococcus epidermidis in one. In the seven of adult patients, two developed sepsis and four died with other organic failures or mediastinal bleeding. All five of infants healed after postoperative 33 to 145 days. The immature state of immune response might associate with postoperative mediastinitis in infants, whether LOS may be important in the immune suppression by surgical stress in adults, and the prognosis of mediastinitis might be effected by prolonged depression of postoperative cardiac function in adult patients. PMID- 8437378 TI - [Computerized recording system during cardiopulmonary bypass utilizing the "GEM 6 PLUS analyzer"]. AB - We developed a new computerized recording system to reduce artificial errors by perfusionists during cardiopulmonary bypass. This system included the efficient functions to record the progress of perfusion flow, perfusion pressure, urine output and temperatures from several sources. Furthermore, it could automatically record considerable data of the "GEM 6 PLUS analyzer" which was developed for monitoring of pH, PCO2, PO2, BE, Ca2+, K+ and hematocrit during cardiopulmonary bypass. We considered it very important that the errors of hematocrits associated with electrolytic concentrations. Therefore, we corrected the hematocrit according to a formula based on our experiments, i.e., HCT = GEMHCT + 0.28 x ([Na+]+[K+]) -44. And also we expect that the "GEM 6 PLUS analyzer" will be improved to measure Na+ value in near future. PMID- 8437379 TI - [Two cases of re-expansion pulmonary edema]. AB - A 62-year-old man and 26-year-old man with re-expansion pulmonary edema (RPE) after thoracic drainage as a treatment for pneumothorax are presented. Blood cell counting and biochemical serum analysis were performed throughout their treatment in both patients, and biochemical sputum analysis was in one patient. The results showed transient marked leukocytosis just after RPE. Total protein and albumin concentrations of sputum approximated to those of serum. The above results suggested that RPE is based on pulmonary microvascular injury, which may introduce leukocytosis. PMID- 8437380 TI - [Combined carotid endarterectomy and coronary artery bypass grafting: a report of two cases]. AB - We reported two cases of successful combined carotid endarterectomy and coronary artery bypass grafting. The first case was a 60-year-old male who had unstable angina pectoris and a history of two times of cerebral infarction. He was revealed to have severe stenosis of left internal carotid artery as well as diffuse stenosis of right and left coronary arteries. The second case, 67-year old male with a history of cerebral infarction, was admitted because of anterior myocardial infarction. Coronary angiography revealed left main trunk disease and carotid angiography also revealed critical stenosis of bilateral internal carotid arteries. We discussed the management of the patients having coexistent such coronary and carotid artery disease. PMID- 8437381 TI - [A case report of central pontine myelinolysis associated with serum hyperosmolality after open heart surgery]. AB - A 65-year-old man was admitted with a sudden onset of dyspnea. Severe mitral regurgitation due to torn chordae tendinae was revealed on UCG. Mitral valve replacement was undergone. The postoperative course was complicated with a low cardiac output syndrome which was successfully treated with IABP, catecholamines and vasodilators. However, stupor developed on the 4 th postoperative day, following by tetrapregia on the 8 th day, and deep coma on the 15 th day respectively. Laboratory studies of the 4 th day disclosed the following values, serum sodium 150 mEq/l, blood urea nitrogen 84.7 mg/dl, blood sugar 184 mg/dl and calculated serum osmolality 354 mOsm/l. Cranial CT of the 15 th day showed an obscure low density area in the central pons which was strongly suggestive of central pontine myelinolysis (CPM). His CNS symptoms improved dramatically after administration of thyrotropin-releasing hormone tartrate (TRH-T). A diagnosis of CPM was made on MRI of the 41 st day. He discharged without any neurological deficit on the 62 nd day. PMID- 8437382 TI - [Surgical treatment of left atrial myxoma with coronary arterial lesion]. AB - We experienced two patients of left atrial myxoma with coronary arterial lesion. One patient, who was a 52-year-old female, was transferred to our institute with the diagnosis of acute myocardial infarction. The coronary angiogram showed an abrupt 99% stenosis of posterolateral branch of circumflex artery with no atherosclerotic lesion, and the echocardiography revealed a left atrial myxoma disturbing the blood flow across the mitral valve. She was in congestive heart failure with pulmonary hypertension, and underwent an emergency removal of the myxoma under cardiopulmonary bypass. Another patient, who was a 70-year-old male, was admitted to our institute with the chief complaint of chest pain. The coronary angiogram showed an 75% atherosclerotic stenosis of the right coronary artery, and the echocardiography revealed the left atrial myxoma. He received a removal of myxoma and a coronary artery bypass grafting simultaneously. These 2 patients went a good postoperative course and live a lively life with no local recurrence. In this paper, the surgical treatment of left atrial myxoma with coronary arterial lesion was reviewed. PMID- 8437383 TI - [Successful aorto-circumflex coronary bypass grafting through left thoracotomy following aortic and mitral valve replacement]. AB - We report successful descending thoracic aorto-circumflex coronary artery bypass grafting using a saphenous vein graft through left thoracotomy in a 44-year-old female. The patient developed severe angina attack after aortic and mitral valve replacement. Coronary angiography showed 99% stenosis of the circumflex coronary artery. Under general anesthesia, left femoral vein to arterial partial cardiopulmonary bypass was performed via left 4 th intercostal space. Body temperature was lowered to 22 degrees centigrade, and spontaneous cardiac fibrillation occurred. After minimal exposure by pericardial dissection of the circumflex coronary artery, distal anastomosis and then proximal anastomosis at the descending thoracic aorta was carried out under cardiac fibrillation. This surgery was done with minimal intra-and postoperative bleeding. Postoperative course was very smooth, and the patient was discharged and leading a normal life for 6 months after surgery. PMID- 8437384 TI - [A case of coronary artery to pulmonary artery fistula associated with impending rupture of saccular aneurysm]. AB - The patient was a 65-year-old woman who was admitted for chest oppression and back pain. Coronary angiography showed an abnormal artery originating from the right coronary artery with the formation of two saccular aneurysms, and draining into the pulmonary artery. The abnormal artery and the aneurysms were resected, and the pulmonary artery was sutured under cardiopulmonary bypass, successfully. PMID- 8437386 TI - [Malfunction of mitral and tricuspid Ionescu-Shiley pericardial xenografts]. AB - We report a case of the malfunction of Ionescu-Shiley pericardial xenografts (ISPX) in the mitral and tricuspid positions at 6 years after implantation. The patient underwent an emergency operation successfully despite his high age (75 years) and extremely poor preoperative condition. The valve extracted from the mitral position showed spontaneous disruption of the leaflet, while the tricuspid valve graft was entangled with the preserved native septal leaflet around the stents. This former complication is now widely recognized, but the latter one appears to be rare. Care should be taken in replacing the atrioventricular valve with a bioprosthesis when the native valve leaflets are not removed. Although the ISPX is no longer in clinical use, careful follow-up is mandatory in patients with this prosthesis especially when it was implanted in the mitral position. PMID- 8437385 TI - [Myocardial revascularization with bovine internal thoracic artery graft (BIOFLOW): a case report]. AB - Bovine internal thoracic artery graft (BIOFLOW) was used for coronary artery bypass grafting (CABG). A 64-year-old woman who had undergone triple CABG with saphenous vein five years ago was referred to our hospital again with anginal attack. Coronary angiogram showed the obstruction of the graft for LAD and new stenosis at right coronary artery (RCA). Gastroepiploic artery was not available because the patient had a history of gastric ulcer several times, and saphenous vein had harvested initial operation. We planned re-CABG for LAD with left internal thoracic artery and RCA with BIOFLOW. But at the operation, LAD was not graftable because of severe calcification. So that we performed single CABG to RCA with BIOFLOW. The BIOFLOW was patent at the 28 th postoperative day. From our experience, BIOFLOW can be expected as a graft for CABG when saphenous vein, internal thoracic artery and gastroepiploic artery are not available. PMID- 8437387 TI - [A case report: surgical repair of bilateral coronary artery-pulmonary artery fistula associated with mitral regurgitation, tricuspid regurgitation and severe renal dysfunction]. AB - The patient was a 72-year-old female who was admitted with evaluation of dyspnea on effort. On cardiac catheterization, coronary angiography showed the fistula from both RCA and LAD to the pulmonary artery and L-R shunt ratio was 37.4%, and MR and TR were found. The preoperative examination showed renal dysfunction, BUN: 61.6 mg/ml, Cr: 21. mg/ml, 24 hr Ccr: 15.2 ml/min. At the operation, the fistula was closed from the inside of the pulmonary artery and MVR (27 SJM) and TAP (Kay Reed method) were performed associated with the intra-operative hemodialysis. The peritoneal dialysis was used for 9 days after the operation. The hemodynamics and the urination were well controlled. A successful surgical repair of bilateral coronary artery-pulmonary artery fistula associated with valvular disease and severe renal dysfunction was reported. PMID- 8437388 TI - [Left ventricular rupture at an atypical place after mitral valve replacement: a case report]. AB - Left ventricular rupture after mitral valve replacement (MVR) is a relatively rare, but a lethal complication. We report a case with this complication. The case was a 62-year-old woman with MSr, TR, and giant left atrium. She underwent MVR with SJM 29 mm, and TAP. During the operation, we found bleeding in the pericardial cavity, and confirmed left ventricular rupture. The place of the rupture was similar to Type I, but it was not posterior atrioventricular wall, but was lateral wall, left side of LAD. We thought that a manipulation during MVR was relevant to this event. Because, this place was opposite the anterolateral commissure of mitral valve to which the chordae tendineae and papillary muscles were adhered. It appeared that the annulus was injured at this point during the operative procedure. PMID- 8437389 TI - [A case of left atrial myxoma with cerebral infarction as initial symptom]. AB - A 75-year-old man with an initial episode of cerebral infarction was found to have left atrial tumor by some noninvasive methods. Tumor was resected through transverse atriotomy. Excised specimen showed left atrial myxoma. Cardiac myxoma should be considered as one of ailments in elderly patients presenting with systemic embolization. PMID- 8437390 TI - Pyrogenic reaction after intravenous injection of pentazocine and methylphenidate. PMID- 8437391 TI - A 33-year-old woman with a propranolol and chlorpromazine overdose, with applied nursing diagnoses. AB - The challenge of emergency nursing comes from opportunities to increase knowledge and integrate it into our clinical practice. We face the challenge of identifying pertinent nursing diagnoses for our patients and linking them with the interventions used in our patients' care. From this information we can verify effectiveness of care and increase nursing's scientific body of knowledge. PMID- 8437392 TI - A formalized approach to obstetric-gynecologic triage. PMID- 8437393 TI - Believing the patient: the lost art of emergency nursing. PMID- 8437394 TI - Analysis through work sampling of the role of the emergency nurse. PMID- 8437395 TI - More on emergency medical technician (EMTs) in the emergency department. PMID- 8437396 TI - More on emergency medical technicians (EMTs) in the emergency department. PMID- 8437397 TI - More on emergency medical technicians (EMTs) in the emergency department. PMID- 8437398 TI - Emergency department Volunteer Liaison Family Communication Program. PMID- 8437399 TI - Determination of the cost of operation for one emergency department. PMID- 8437400 TI - More on emergency medical technicians (EMTs) in the emergency department. PMID- 8437401 TI - Pennsylvania paramedic legislative issues. PMID- 8437402 TI - The myth of 100% oxygen delivery through manual resuscitation bags. AB - OBJECTIVE: To determine the actual oxygen delivery of the manual resuscitation bags (MRBs) hanging at the bedsides of patients receiving mechanical ventilation. DESIGN: Descriptive study of 24 MRBs in use at the patient's bedside from six adult ICUs at a 1100-bed Mid-Atlantic medical center. METHODS: MRBs were Puritan Manual Resuscitators with reservoir. Oxygen concentration delivered was measured with a Ventronic Oxygen Analyzer Model 5575. Oxygen flow to the MRB was recorded before collecting data and then set at 15 L/min. The MRBs were compressed three times, with a 5-second interval between compressions. RESULTS: Oxygen flow before data collection varied from 6 L/min to 15 L/min. Measurements taken at the exit port before MRB compression ranged from 23% to 97%. Oxygen concentration ranged from 26% to 95%, with a mean of 59%. The oxygen values for each compression time were significantly lower than 100% (p < 0.001). The first compression values differed significantly from the second compression (p < 0.001) and the second differed from the third compression (p < 0.01). CONCLUSION: MRBs are not delivering the level of oxygen nurses have assumed. In addition, variation in oxygen delivery occurs from compression to compression. PMID- 8437403 TI - Families and codes--one emergency department's experience. PMID- 8437404 TI - Colored baseball caps identify disaster team members. PMID- 8437405 TI - Emergency department phone triage record. PMID- 8437406 TI - Mergers and acquisitions: consolidating two emergency departments. PMID- 8437407 TI - Restraining patients: can you be sued? Part II. PMID- 8437408 TI - An unusual air bag-mediated injury. PMID- 8437409 TI - Packaging and labeling change for potassium chloride concentrate. PMID- 8437410 TI - Tips for the new nurse educator: thoughts one year after beginning the role. PMID- 8437411 TI - Infant colic. PMID- 8437412 TI - The Model Trauma Care System Plan. PMID- 8437413 TI - Part nurse, part daughter. PMID- 8437414 TI - An unusual case of weakness and apnea in a 37-year-old female addict. PMID- 8437415 TI - Pediatric emergency department nurse manager Olga Dale: innovator and staff nurse advocate. Interview by Marlene Jezierski. PMID- 8437417 TI - Croatian nurse corresponds with author. PMID- 8437416 TI - More on trauma resuscitation flow sheet. PMID- 8437418 TI - More on trauma scoring and pediatric patients. PMID- 8437419 TI - [Chemoprophylaxis for children exposed to tuberculosis]. PMID- 8437420 TI - [A case of pulmonary tuberculosis complicated with drug toxicosis--value of shosaikoto and hochuekito as anti-allergic agents]. AB - A clinical course of pulmonary tuberculosis was reported about adverse reaction of anti-tuberculous chemotherapy. A fifty-eight-year-old male patient was complicated with agranulocytosis induced by RFP, hepatic dysfunction and systemic eruption induced by INH, and high fever induced by SM. Adjuvant therapy with Shosaikoto and Hocheukito suppressed INH induced hepato-dermatological toxicosis moderately and suppressed SM induced high fever completely. By these anti allergic therapy, combined chemotherapy with SM, EB, PAS and PZA became possible during more than six months, and chemotherapeutic effect was marked. This case report suggested possibility and significance of those Kampo agents against serious allergic reaction complicated with the chemotherapy for pulmonary tuberculosis. PMID- 8437421 TI - [Progress in clinical microbiology of Mycobacterium avium complex and prospect on its future]. AB - Recent advance of technology in isolation and identification methods for mycobacteria, including BACTEC 460 TB System, polymerase chain reaction (PCR), DNA probe test, etc., enabled us to perform rapid and accurate identification of mycobacterial pathogens from various clinical specimens. Our recent study revealed usefulness of BACTEC 460 TB System, on the basis of the high efficiency in detecting the organisms in sputum specimens with much shortened recovery time, as compared to the Ogawa method. Moreover, accurate identification was possible, when the diagnostic system was combined with AccuProbe test. PCR using appropriate primers specific to Mycobacterium, M. tuberculosis complex (MTC), or M. avium complex (MAC) is useful to detect mycobacterial organisms directly in clinical specimens in a rapid manner. By this technique, in particular nested PCR, it is now possible to detect very small number of the organisms, as few as one bacterium, in test specimen, although it is still needed to resolve some difficulties due to contaminating inhibitors in the specimens. In our nested PCR system using Mav17 and Mav18 primers specific for Mycobacterium, especially MAC, we found that detectable degree of DNA amplification was possible even by replacing purified DNA sample, extracted from the organisms by considerably time consuming procedures, with bacterial suspension as a DNA template, by adding about 10(4) of organisms. The three DNA probe testings, Gen-Probe, AccuProbe and SNAP kits, are useful for rapid identification of MAC, MTC, M. kansasii and M. gordonae, and consistent results were obtained by these diagnostic kits. SNAP is able to distinguish the X component of MAC from the other two types of MAC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437422 TI - [The epidemiology of pulmonary disease caused by Mycobacterium avium complex in Japan]. AB - The number of the patients of active lung tuberculosis and nontuberculous lung mycobacteriosis (NTM) admitted to the 97 sanatoriums in Japan were studied. The number and the prevalence rate of tuberculosis did not decrease during the years from 1985 to 1990, indicating the prevalence rate of 43.1 in 1990 per 100,000 population. Nevertheless, the number of NTM has gradually increased in these 6 years. The prevalence rate of NTM and pulmonary M. avium complex disease (MAC) calculated were 4.18 and 2.46 in 1985, increasing to 6.90 and 4.53 in 1990. Consequently, annual number of the patients newly infected with MAC was suspected to be approximately 5500 in 1990 in Japan. These infections occurred principally in South-West of Japan in the previous years, and were not so common in northern part of Japan. However, a remarkable increase in the number and the prevalence rate of MAC infection has also been noted in northern part of Japan in these 6 years. The number of MAC patients distributed equally in both sexes and the average age was 67 years. The 60% of the patients had some underlying diseases. PMID- 8437423 TI - [Skin reaction test using PPD-B]. AB - Inapparent infection caused by Mycobacterium avium-M. intracellulare complex was examined in healthy persons by skin reaction tests using purified protein derivatives of M. intracellulare ATCC 19530 (PPD-B). Skin reaction to PPD-B was evaluated as positive, as it was for PPDs, when the diameter of the reaction (redness) was 10 mm or more, and it was evaluated as significantly positive when the reaction was the same or larger than that to PPDs. Examination of 379 volunteers (ages 18-53, one female only) from the Kaitaichi Station, Ground Self Defence Force gave the following positive and significantly positive rates by age respectively: 12.8% and 10.3% for ages 18-19, 25.8% and 9.0% for ages 20-29, 39.7% and 12.8% for ages 30-39, and 51.2% and 15.5% for ages 40-53, and the rates were 32.7% and 11.1% for all ages combined. The positive rates to PPDs, on the other hand, were 33.3% for ages 18-19, 65.7% for ages 20-29, 91.0% for ages 30 39, and 95.2% for ages 40-53, and the rate was 74.1% for all ages combined. The PPD-B positive rate increased with age from 12.8% at 18-19 years of age to 51.2%, but the significantly positive rate showed no significant increase. Evaluation to PPD-B and PPDs were both positive, because of the difficulty of determining clearly whether the cause was M. tuberculosis and M. avium complex infection or cross reaction of skin reaction to PPDs and PPD-B. PMID- 8437424 TI - [Evaluation of DNA-DNA hybridization method for identification of mycobacteria using a colorimetric microplate kit]. AB - DNA-DNA hybridization was applied for identification of mycobacteria and developed as a kit "microplate hybridization kit" (refers to MPHD) by Kobayashi Pharmaceutical Co. We received test samples of the microplates from the company and examined them for their and reliability using 180 mycobacterial strains of 21 species kept in our laboratory. The results of identification by MPHD were 100% identical to those of biochemical identification in the type or reference strains of mycobacteria, showing good reliability of MPHD method. Among clinical isolates, there were six M. tuberculosis strains which did not show typical characteristics for M. tuberculosis, i.e., niacin test negative or nitrate reduction weak positive, but all of these were identified as M. tuberculosis complex by MPHD method. Some strains from clinical isolates showed difference in identification between MPHD and biochemical methods: M. avium complex, identified biochemically were divided into M. avium and M. intracellulare by MPHD, M. fortuitum complex by biochemical identification were distinguished as M. fortuitum and M. chelonae by MPHD. Further, M. chelonae were separated into M. chelonae subsp. chelonae and M. chelonae subsp. abscessus by MPHD. M. peregrinum has been considered as a synonym of M. fortuitum, but we could distinguish M. peregrinum from M. fortuitum clearly by MPHD method. Thus, it is suggested that M. peregrinum and M. fortuitum are different species. Keys for getting reliable results using the MPHD kit are: (1) appropriate amount of bacteria for use, (2) purification of DNA, (3) enough deproteinization, and (4) appropriate timing to read colorimetry measurement of the plate. PMID- 8437425 TI - [Clinical features of the patients with "primary infection" of Mycobacterium avium complex]. AB - Clinical characteristics are analysed in patients with primary infection of Mycobacterium avium complex (MAC). The definition of primary infection of MAC are determined as follows; 1) MAC is found several times since the beginning of the disease, 2) clinical symptoms or abnormal shadows on chest roentgenogram corresponding to MAC infection, 3) no old tuberculous lesions nor other abnormal shadows like bronchectasis, 4) no abnormal serological results suggesting other bacterial or viral infections. According to this definition, 17 out of 84 MAC patients are diagnosed as primary MAC infection, and clinical features are analyzed in these 17 patients. Average age of patients is 61.1 +/- 12.9 year old. This age is significantly higher than that of inpatients with pulmonary tuberculosis in our hospital, and lower than that of all MAC patients including primary and secondary infection. Five (29.4%) are male and 12 (70.6%) are female, the ratio of male to female is 1 to 2.4. This value is significantly different with that of inpatients with pulmonary tuberculosis in our hospital which revealed about 3 to 1. Most of the patients complained of cough with sputum, especially of hemosputum. Eleven patients (64.7%) out of 17 patients complained of repeated hemosputum. The frequency of hemosputum is very high compared with that of the patients with pulmonary tuberculosis (about 20%). No compromised condition was present except for a patient with Behcet's disease who was taking steroid hormone. Roentgenographic features of primary infection of MAC are those of scattered small nodular lesions in the peripheral part of the lung, thin wall cavity formation, no contraction of the diseased lung nor dislocation of the trachea.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437426 TI - [Clinical features of the patients with "secondary infection" of Mycobacterium avium complex--Radiographic pattern of progressions in the patients with and without underlying pulmonary conditions]. AB - We reviewed the radiographic features of 42 patients with Mycobacterium avium complex (MAC) infection. Six cases were definite "primary", 20 were "secondary", and 15 were indeterminate (probably "primary"). In the definite and probable "primary" cases, and some of the "secondary" cases, pulmonary lesions slowly progressed following a common and characteristic sequence from a cluster of small nodules or fibro-productive nodules to those with subpleural thickening, or with thickening of the draining bronchi, or with both subpleural and bronchial thickening, and to cystic bronchiectatic changes associated with collapse of the segment or the lobe, in the final stage. Cases of airspace pneumonia appeared rarely. In these cases, neither apical-subapical region prevalence, pleural effusion, nor mediastinal lymphadenopathy were found. On the contrary, in five cases of "secondary" infection, MAC lesions located at the same place with the predisposing lung disease and did not progress during more than five years of observation. In the progressive cases of "secondary" infection, however, the appearance of new lesions and the progressions thereafter showed the same pattern as in "primary" infection. These features would suggest that MAC infection would occur and progress slowly among patients who had unknown pathogenetical factor, whether they had underlying predisposing lung conditions or not. PMID- 8437427 TI - [Clinical features of the lung diseases due to Mycobacterium avium and M. intracellulare]. AB - In recent years, it has been made easy to identify Mycobacterium avium and M. intracellulare by DNA-probe test. To evaluate possible clinical differences between the lung diseases due to M. avium and those due to M. intracellulare, we studied a total of 248 cases (136 due to M. avium and 112 due to M. intracellulare). M. avium cases were found more frequently in the eastern part of Japan, whereas M. intracellulare cases were seen more frequently in the western part of Japan. There was no significant difference between M. avium cases and M. intracellulare cases in sex, age, complications, chief complaint, body weight, tuberculin skin test, erythrocyte sedimentation rate, serum protein content, findings of chest X ray. M. avium cases were more frequently detected by health examination. M. avium was more susceptible to cycloserine than M. intracellulare. On the other hand, M. intracellulare was more susceptible to streptomycin and kanamycin. The prognosis of M. intracellulare cases were better than M. avium cases, when compared only the patients who showed positive tuberculin skin test. PMID- 8437428 TI - [Immunological aspects of Mycobacterium avium complex infection]. AB - Tuberculin anergy is common in patients with Mycobacterium avium complex (MAC) infection. We examined in vitro cell-mediated immunity in these patients with MAC infection. Peripheral blood lymphocytes of patients, as compared with those of tuberculous patients or tuberculin-positive healthy donors, showed depressed in vitro blastogenic responses to purified protein derivative of tuberculin (PPD), not only to PPDs of Mycobacterium tuberculosis but also to PPD-B and PPD-Y of M. intracellulare and M. kansasii, respectively. Analysis of defective in vitro PPD induced lymphocyte blastogenic responses in these patients revealed that PPD induced interleukin 2 (IL-2) production was impaired whereas PPD-induced IL-2 responsiveness was normally developed after PPD stimulation. In the second half of this report, study was carried out to examine the mechanism of depressed T cell activity in these patients. Heat-killed MAC organisms and their lipid component impaired the capacity of peripheral blood lymphocytes to proliferate in vitro in response to concanavalin A (Con A), PPD, and to a lesser degree, phytohemagglutinin (PHA) stimulation. Inhibition by MAC was not contingent upon prior exposure of the donor to MAC or other mycobacteria and occurred with lymphocytes from tuberculin-negative as well as -positive subjects. The suppression was not due to the toxicity of MAC. Adherent cell depletion and cell mixing experiments with T cells indicated that monocytes and not T cells were a major contributor to the immunosuppression observed. Treatment of monocytes with MAC or MAC-derived lipid resulted in significant decreases in CD11b, a member of the LFA-1 and Leu M3 (CD14) molecule.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437429 TI - [AIDS and Mycobacterium avium complex infection]. AB - Infections with Mycobacterium avium complex (MAC) are the next most common complication in AIDS patients, and disseminated MAC infection is considered as an indicator disease of AIDS. Bacteriological and clinical features of MAC infection complicated with AIDS were reviewed. The number of AIDS patients in Japan has been increasing in a similar rate as in USA and Africa, so the members of Japanese Society for Tuberculosis should be ready for medical care of AIDS patients complicated with mycobacterial infections. PMID- 8437430 TI - Removal of blood from laboratory mammals and birds. First report of the BVA/FRAME/RSPCA/UFAW Joint Working Group on Refinement. PMID- 8437431 TI - Cannulation of the lateral saphenous vein--a rapid method to gain access to the venous circulation in anaesthetized guinea pigs. AB - Previously published methods of venous puncture in guinea pigs did not provide reliable venous access for more than a few minutes, and therefore surgical intervention was necessary to cannulate the femoral or external jugular vein or the vena cava. In the present report cannulation of the Vena saphena lateralis via the Vena plantaris lateralis or of the Vena saphena medialis is described by inserting a 22 gauge teflon catheter. These catheters are commercial products. The method is timesaving and inexpensive. Successful cannulation was accomplished in 34 of 35 guinea pigs. No lethal incidents occurred. PMID- 8437432 TI - Practical venipuncture techniques for the ferret. AB - As the number of ferrets (Mustela putorius furo) used in research and kept as pets continues to rise, so does the need for simple, humane research and diagnostic techniques. We have developed venipuncture methods for the ferret utilizing the jugular and cephalic veins. Using these methods it is possible to repeatedly sample moderate volumes of blood and to perform intravenous injections in both conscious and sedated ferrets. PMID- 8437433 TI - Responses of laboratory animals to some injectable anaesthetics. AB - Xylazine, ketamine, methohexitone and alphadalone/alphaxalone, were administered intraperitoneally, intramuscularly or intravenously to mice, rats, guinea pigs and rabbits. Times for disappearance and reappearance of reflexes were recorded, and duration of loss of reflex. Delivering a predetermined dose gave a varying individual response, ranging from inadequate anaesthesia to death. Using reflexes to assess depth of anaesthesia was of limited value. Reflex movements to noxious stimuli generally persisted even at dose rates that caused prolonged recovery times and death. Conversely, in rats there was no response to a cutaneous stimulus in some animals even though recumbency was almost restored. PMID- 8437434 TI - Inter-colony variation in fluid balance and its relationship to vasopressin secretion in male Sprague-Dawley rats. AB - Salt and water balance and vasopressin secretion were measured in three colonies of Sprague-Dawley rats. Although sodium and water retention were similar between the groups, there were marked differences in both the rate and diurnal pattern of intake and excretion. Animals housed under semi-barrier conditions showed a lower basal plasma vasopressin concentration but were more sensitive to physiological stimuli. However, since pathogenic status and environmental conditions cannot entirely explain these results, genetic variation is likely to be a contributory factor. PMID- 8437435 TI - Prosthetic microvenous grafting in the rat femoral vein. AB - Male Wistar rats were used to evaluate microvenous prosthetic grafting techniques and microvenous prostheses in the femoral vein. With the end-to-end technique to implant microvenous prostheses, there was extensive exposure of vessel wall collagen especially at the suture sites. Thrombus formation then led to complete occlusion in all but one of the 32 prostheses 60 min after implantation. However, with the sleeve anastomotic technique there was only minimal exposure of collagen and minimal thrombus accumulation. Fifty-nine of the 64 microvenous prostheses implanted with the sleeve technique were patent after 1 day, 1, 3, 6, and 12 weeks (patency rate 92%). All patent microvenous prostheses were completely covered by an endothelial layer after 3 weeks. It was concluded that the rat is an appropriate experimental laboratory animal for evaluating new grafting techniques with microvenous prostheses and that the sleeve anastomotic technique gives the highest patency rates with microvenous prostheses. PMID- 8437436 TI - The inheritance and breeding results of hairless descendants of Mexican hairless dogs. AB - The inheritance and breeding results of hairless descendants of Mexican hairless dogs (MHDs) were investigated. When the male hairless dogs were bred to female beagles, the birth ratio of hairless and haired dogs was 1:1. Mating between MHDs gave both hairless and haired pups. The results indicated that an autosomal dominant monogenic gene was responsible for their hairless characteristics. We propose the symbol Hm for this gene (hairless, Mexican type). The survival rate of hairless pups was markedly lower than that of haired ones. It was elevated to 50-90% by warming their cages to a minimum of 25 degrees C. PMID- 8437437 TI - Folic acid and vitamin B12 status of vervet monkeys used for nutritional research. AB - Plasma and red blood cell (RBC) folic acid levels, as well as plasma vitamin B12 levels were determined in Vervet monkeys (Cercopithecus aethiops). All the vervets were apparently healthy and without symptoms or lesions typical of folic acid and/or vitamin B12 deficiencies. Competitive protein binding radioassays were used to determine folate and vitamin B12 values in animals fed 4 different diets. The B12 levels for all the groups ranged between 866 and 5867 pg/ml and showed an inverse relationship with the FA measurements. The lowest mean RBC folic acid content in a group fed an atherogenic diet for 3 years was 12.8 ng/ml. For the other 3 diets, mean RBC folic acid levels were 90.7, 132.3 and 152.8 ng/ml, respectively. A megadose of 25.6 mg of folic acid per day for 99 days was given to 3 adult males. No obvious toxic effects were observed in these animals although mean RBC folic acid levels increased to 1013 ng/ml. PMID- 8437438 TI - The variability of organ weight background data in rats. AB - The variability of organ weight data in a series of 5 control groups of Sprague Dawley rats was studied. Differences in body weight and organ weight data were detected between the studies. Attempts to reduce the variability of organ weights by using analysis of covariance or organ to brain weight ratios were only partially successful. Factors which may influence animals under controlled conditions and result in variability between studies are discussed. It is concluded that caution is needed when considering the use of organ weight background data as a means of comparison. The findings are in agreement with other fields of study in toxicological testing, and emphasize the importance of using a concurrent control for the purpose of comparison of data. PMID- 8437439 TI - Grass pollen specific antibody in the plasma of normal dogs. AB - An investigation carried out with healthy beagle dogs showed that their plasmas contained detectable levels of grass pollen specific IgG antibody, as measured by a radiometric assay involving the binding of IgG to radio-iodinated staphylococcal protein A. These samples did not, however, contain detectable homocytotropic-type antibodies specific for grass pollen extract. PMID- 8437440 TI - Host specificity of cloned Spironucleus sp. originating from the European hamster. AB - In vivo experiments with a clone of the intestinal flagellate Spironucleus sp. originating from the laboratory European hamster (Cricetus cricetus), and the comparison with a spontaneous infection from laboratory bred European hamsters suggest high specificity of this clone for the homologous host. Only the Syrian golden hamster (Mesocricetus auratus) could be infected experimentally, though the mean intensity of infection was lower. Other heterologous recipients, mice and rats of one outbred and one inbred strain each, could not be infected. Even immunodeficient mice (athymic and C.B-17-scid) remained uninfected after inoculation of 5 x 10(5) cysts per mouse. This is the second Spironucleus clone, after the rat isolate (Schagemann et al., 1990), with a high level of host specificity suggesting heterogeneity within the genus Spironucleus. PMID- 8437441 TI - [Smokeless occupational environment--human right or patronizing?]. PMID- 8437442 TI - [Do maternal benefits mean worse maternal health services?]. PMID- 8437443 TI - [Account for facts on pediatric surgery!]. PMID- 8437444 TI - [Integrated responsibility--reduced territory]. PMID- 8437446 TI - [Children with chronic ITP, a small but forgotten group?]. PMID- 8437445 TI - [Free establishing--the guidelines are clearer]. PMID- 8437447 TI - [Suspected ureteral obstruction in the fetus. When to do what?]. PMID- 8437448 TI - [Empathic disorders. Fundamental in different severe psychiatric handicaps?]. PMID- 8437449 TI - [Weight deviation. A measure of psychosocial health in children of mentally retarded mothers]. PMID- 8437451 TI - [Nitrous oxide is not necessary in propofol anesthesia]. PMID- 8437450 TI - [Staph saprophyticus urinary tract infection. Spontaneous remission is rare but pivmecillinam is effective]. PMID- 8437452 TI - [When the bride turns pale--is it anemia?]. PMID- 8437453 TI - [Acute ischemia of the extremities. Importance of correct diagnosis]. PMID- 8437454 TI - [Therapy of whooping cough. Treatment for the "privileged", what about the others?]. PMID- 8437455 TI - [A legend from Bangladesh received an alternative Nobel Prize]. PMID- 8437456 TI - [The university hospital--problems and solutions. Avoid centralization of research!]. PMID- 8437457 TI - [The university hospital--desired development?]. PMID- 8437458 TI - [Keep the lifeline!]. PMID- 8437459 TI - ["Manipulation" in the anamnesis]. PMID- 8437460 TI - [Cervical manipulation is an excellent method]. PMID- 8437461 TI - [New maternal insurance increases freedom of choice and quality of care]. PMID- 8437462 TI - [Educate workers to worry about problems in advance!]. PMID- 8437463 TI - [The Ljusdal method is not considerate]. PMID- 8437464 TI - [(The Ljusdal method) cannot be recommended]. PMID- 8437465 TI - [The role of radiotherapy in cancer care. Improved technique results in optimal treatment]. PMID- 8437466 TI - [5-HT receptors. Significant target group in the treatment of migraine]. PMID- 8437467 TI - [Malignant melanoma of the conjunctiva. It is important to know about this unusual tumor]. PMID- 8437468 TI - [Drug dependence. Ambulatory treatment with contact support and gradual dose reduction yield good results]. PMID- 8437469 TI - [Close-shaven women, victims of mud-wrestling disease]. PMID- 8437470 TI - [An effective method for treatment of pressure sores. Total reduction of pressure supersedes the turning schedule]. PMID- 8437471 TI - [Exposure to tear-gas is more frequent. Risk of pulmonary effects and eye injuries]. PMID- 8437472 TI - [Severe hand injuries caused by power lawn-mowers. Deadman's grip, a very effective preventive measure]. PMID- 8437473 TI - [Alarming figures on homelessness. Are the positive trends changing?]. PMID- 8437474 TI - [A new type of test with external examinations. Both the practical and the theoretical knowledge is tested]. PMID- 8437475 TI - [Specialist examination in clinical chemistry. Voluntary examination for higher competence]. AB - The Swedish Society for Clinical Chemistry has now completed its second board examination for voluntary specialist diploma in clinical chemistry. The first day comprised a 6 hour written examination (about 20 essay questions). The second day was an oral examination in front of five clinical chemists representing different aspects of the specialty, firstly as questions on the subject as a whole and secondly in the form of a seminar where original research work carried out by the examinee was discussed. PMID- 8437476 TI - [Kallmann syndrome. Diagnosis is based on the absence of puberty and olfactory sense]. PMID- 8437478 TI - [To call or not to call? That is the question]. PMID- 8437477 TI - [The man behind the syndrome. A pioneer in the research of schizophrenia]. PMID- 8437479 TI - [Calling systems are very good!]. PMID- 8437480 TI - [Sequelae of abuse as a concealed cause of disease]. PMID- 8437481 TI - [Political reform with medical content. Neutrality in problems with general practice is not possible]. PMID- 8437482 TI - [Tuberculous meningitis still a reality]. PMID- 8437483 TI - [Towards health services close to the workplace]. PMID- 8437484 TI - [Creative research environment in Umea]. PMID- 8437485 TI - [More about viper bites]. PMID- 8437486 TI - [Are children of brain-dead women to be saved?]. PMID- 8437487 TI - [The zero hypothesis "proven"--a common misunderstanding]. PMID- 8437488 TI - [Healthier life style among young people. Prevention, priorities, politics]. PMID- 8437489 TI - [The elderly hypertensive patient. Increased indications for treatment]. PMID- 8437490 TI - [Pharmacological treatment of hypertension. Low frequency of adverse effects in the elderly]. PMID- 8437492 TI - [Humanistic view of the problem of suicide. Increased self-insight increased understanding]. PMID- 8437491 TI - [Vocal cord paralysis should be followed up for malignancy. High probability of paralysis resulting from cancer]. PMID- 8437493 TI - [Adolescent health habits and risk behavior. Intensive concentration of the municipalities for better health]. PMID- 8437494 TI - [Treatment of tumor diseases with biological methods]. PMID- 8437495 TI - [Axillary lymph node dissection in malignant melanoma]. PMID- 8437496 TI - [Rupture of an aneurysm of the common hepatic artery with pancreatic necrosis]. AB - A male patient known to have hemophilia A was operated on twice (1990, 1991) in the Department of Surgery, University Hospital, Zurich, first because of severe intraabdominal hemorrhage from a liver artery aneurysm, and then because of a ruptured common hepatic artery aneurysm. The second surgical intervention revealed necrosis of the head and body of the pancreas. We consider that the pancreatic necrosis had resulted from the aneurysm, in view of the patient's history of silent pancreatitis and the uncomplicated postoperative course. Immediate reconstruction of the common hepatic artery aneurysm (in the presence of an occluded gastroduodenal artery) was performed with saphenous vein interposition. Because visceral aneurysms may be multiple, further aneurysms must be sought at the time of the first diagnosis. Elective surgery is the method of choice, because 40-80% of visceral aneurysms rupture spontaneously, with a high mortality rate. The mortality rate for elective surgery is now low. PMID- 8437497 TI - [Cardiocirculatory side effects of hyperthermic extremity perfusion]. AB - The risk of cardiocirculatory disorders was investigated in 23 consecutive patients with high-risk melanomas, who had been treated with hyperthermal limb perfusion. Postoperatively, there was a rise in the pulmonary vascular resistance. In addition, 14 patients with vascular occlusive diseases (1-2b, Fontaine) showed intraoperatively an increasing amount of leakage of the extracorporeal circulation. Elevations of thromboxane and prostacyclin in excess of the norm caused by mechanical and thermic traumatization of blood in the heart lung machine were detected in 8 patients investigated during and after the perfusion procedure. Significant increase of cisplatin, one of the two cytostatic agents injected extracorporeally, could not be demonstrated in the blood of the systemic circulation by atomic absorption spectroscopy. Increased pulmonary and arterial pressure disorders were observed in the group with occlusive vascular diseases, caused by a rising rate of vascular collaterals to the body and the rising rate of thromboxane and prostacyclin in the body blood flow. We believe that it is necessary to monitor pulmonary arterial pressure during isolated limb perfusion, especially in patients with vascular occlusive disease. PMID- 8437498 TI - [Technique and results of hyperthermic perfusion of the extremity in melanoma patients]. AB - The results of hyperthermic isolated limb perfusion therapy in 36 patients with stage II-IV malignant melanoma of the extremities are presented. With the technique employed, neither severe complications nor functional deficiencies attributable to the perfusion therapy were observed. The findings on follow-up for up to 36 months are comparable to those reported in the literature, with survival rates of about 90% for stage II and III patients and nearly 50% for stage IV patients. Thus, our technique appears to be beneficial, especially in respect of the very low rate of side effects. PMID- 8437499 TI - [Actuarial survival and prognostic factors of bronchial cancer]. AB - A total of 1325 patients with bronchogenic carcinoma who were treated at the surgical clinic of the Technical University of Munich between 1981 and 1991 were enrolled in a prospective follow-up study. The 5-year actuarial survival rate of 605 patients with squamous cell carcinoma was 28.2%, of 288 patients with adenocarcinoma 38.0%, of 219 patients with small cell carcinoma 15.4%, of 74 patients with giant cell carcinoma 19.0%, and of 139 patients with other histologic findings 27.8%. In all, 680 patients (51.4%) underwent surgery. Diagnostic thoracotomy without resection was performed in 6.2% of cases. Lethality within 30 days was 1% for lobectomy, 7.3% for bilobectomy, and 7.7% for pneumonectomy including extended resections. The 5-year survival rates among the operated patients were 64.8% for T1N0M0 tumours, 49.4% for T2N0M0, 46.1% for T1N1M0, 43.4% for T2N1M0, 23.8% for T3 and 11.7% for T4. T1N0M0 adenocarcinoma was associated with a better prognosis than squamous cell carcinoma of the same early stage, with a 5-year survival rate of 82.2% vs 55.9%. The prognosis of patients with T3N2 was worse than that of patients with a T3-4 primary tumour but only N0-1 lymph node involvement (5-year survival rate 18.1% vs 31.7%). Stepwise logistic regression analysis identified tumour stage, therapy, and histologic result as the factors with the greatest impact on the prognosis. Adjuvant radiation after resection in patients with T2-3 adenocarcinoma or squamous cell carcinoma improved the prognosis by one tumour stage compared with patients who only underwent surgery. In conclusion, surgical therapy of bronchogenic carcinoma offers favourable survival rates with acceptable risk.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437500 TI - [Value of adjuvant local antibiotic administration in therapy of open fractures. A comparative analysis of 704 consecutive cases]. AB - Seven hundred and four compound fractures--198 (28%) grade I, 259 (37%) grade II, 247 (35%) grade III (86 IIIA, 119 IIIB, 42 IIIC)--were treated in 590 patients between May 1983 and May 1989 at the University of Louisville. Of these fractures, 157 (22%, group 1) received systemic antibiotic prophylaxis only, whereas 547 (78%, group 2) were treated with additional local application of aminoglycoside beads (tobramycin). Comparison of factors (fracture grades, age, sex, fracture location, follow up) revealed no significant differences between the two groups. All fractures underwent timely irrigation, debridement and skeletal stabilization. In group 1, 52 wounds were primarily closed, 53 underwent delayed primary closure and 52 were left open. In group 2 283 wounds were primarily closed, 229 were managed with the bead pouch technique and 35 were adapted loosely (delayed closure). Forty-nine (6.96%) of the 704 compound fractures became infected (acute wound infection and/or chronic osteomyelitis). Group 1 showed an infection rate of 16.6% (26/157), group 2 a rate of 4.2% (23/547). The difference was statistically highly significant (P < 0.001). Comparison of the infection rates, whether on an acute or a chronic basis, showed that infection rates were lower in group 2 than in group 1 for all fracture grades. A statistically significant difference was established only for type IIIB fractures, where the wound infection rate was 39.1% (9/23) in group 1 and 7.3% (7/96) in group 2 (P < 0.001). The rate of chronic osteomyelitis was 26.1% (6/23) in group 1 and 6.3% (6/96) in group 2 (P < 0.025).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437501 TI - [Malignant adrenal pheochromocytoma--problems in evaluating clinical diagnosis and morphologic extent]. AB - Reports on three patients with malignant adrenal phaeochromocytoma are used as a basis for discussion of involved in diagnosing functionally inactive paragangliomas and in discriminating between benign and malignant adrenomedullary tumours. Malignancy can so far only be ascertained in such neoplasms by evidence of metastatic growth. Our findings, however, show that increased tumour weight (more than 200 g), high mitotic activity (more than 5 mitoses per HPF) and loss of S-100 protein-positive subtentacular cells make it possible to distinguish high-risk cases (with increased risk of recurrence and metastasis). PMID- 8437502 TI - [Axillary recurrence after lymph node excision in malignant melanoma]. AB - In a retrospective study 143 patients with 155 axillary lymphadenectomies were observed with a maximum of 8 years of follow-up (mean 51.9 +/- 25.8 months). At the time of their lymphadenectomies, 39 patients had histologically negative nodes (stage I), 85 patients lymph-node metastases (stage II), 19 patients axillary node involvement and distant metastases (stage III). The estimated 5 year survival rates were 77.5% in stage I and 28.6% in stage II. Axillary recurrence after dissection of tumor-free lymph nodes rarely happened, but in stage II the probability of recurrence was as high as 30.7%. All axillary recurrences occurred in the first 20 months after lymphadenectomy. In a multivariate analysis (Cox model), the only prognostic factor of probability of recurrence in stage II was the development of regional in-transit cutaneous metastases (p = 0.048). Factors that did not affect the appearance of recurrent metastases in the node dissection field were: epidermal ulceration, vascular invasion, tumor thickness, degree of lymph-node involvement, age, sex, and adjuvant chemotherapy. Median survival after axillary recurrence following therapeutic lymph-node excision (5 months) was comparable with survival after lymphadenectomy in stage III (7 months). There was a high incidence (> 30%) of regional in-transit cutaneous metastases in both groups. Regardless of the poor prognosis, we found 15% axillary recurrences after lymph-node clearance in stage III. PMID- 8437503 TI - [Studies of lipid and lipoprotein metabolism in man after surgical interventions]. AB - The pattern of serum lipids and lipoproteins was investigated before and after surgery in 77 patients with respect to the "acute-phase reaction". Special attention was paid to the severity of the surgical trauma and the time course of postoperative alterations. Therefore, 12 different serum parameters were measured in 18 patients just before surgery and on days 1, 3, 5 and 10. From the results of this sample, patients in the main trial were divided into three groups with different degrees of trauma: group 1 (n = 22) with low surgical trauma; group 2 (n = 20) with extensive abdominal operations; group 3 (n = 17) with total endoprosthesis of the hip. A 25-40% perioperative decrease in cholesterol, triglycerides, lipoprotein classes (alpha-, beta- and pre-beta-lipoproteins) and apolipoprotein A1 and B was found during the first 24 h after surgical trauma. Thereafter, the above parameters showed a tendency toward more or less complete normalization by day 10. In contrast, C-reactive protein (CRP), initially increased by a factor of 8-10, returned to the normal concentration range by postoperative day 10. The amount of cholesterol loss was low in group 1 (-16%), but considerable in group 2 (-38%) and group 3 (-35%) when compared with preoperative levels. This cholesterol loss was mainly due to a decrease in beta lipoproteins (LDL), but also in alpha-lipoproteins (HDL). It can be concluded from these results that a sudden decrease in cholesterol containing serum lipoproteins occurs in relation to the size of a surgical trauma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437504 TI - [Acquired disorders of peritoneal cavity muscles. Abdominal wall denervation in pregnancy, denervation incontinence, and continent and incontinent constipation]. AB - The peritoneal cavity has a fascial skeleton that is kept under tension by permanent variable resting tone maintained by the abdominal muscles. The lateral abdominal muscles, the diaphragm and the pelvic floor are all components of this fasciomuscular support system. Voluntary and reflective changes in muscle tension allow the entry and exit of matter into and out of the spherical abdominal cavity by opening and closing of specialized wall segments called sphincters. We have previously demonstrated the existence of a resting tone in the tail muscles of mammals from which the human pelvic floor muscles are derived. The pelvic floor and its integrated sphincters form the anorectal organ of continence. This organ is much weaker in females than in males. The spinal centers that govern continence, contain in the female significantly fewer ganglion cells than the corresponding centers in the male. Childbirth and a commonly found tendency to develop constipation are additional stressors for the congenitally weaker female organ of continence. We explain in this paper why the abdominal wall and the pelvic floor may suffer stretch-induced denervation injuries during pregnancy and delivery. Such damage may persist in later life and can give rise to incontinence and "flabby abdomen". Based on our work in this field, we found a new differentiation between continent and incontinent constipation. Continent constipation is caused by spasticity of the pelvic floor characterized by abnormally high sphincter activity. This spastic pelvic floor syndrome can be treated successfully by psychotherapeutic techniques. Incontinent constipation, in contrast, is always associated with subnormal activity of the sphincters and may be a cause of rectal prolapse. It can be treated successfully by anterior rectosigmoid resection. Incontinent constipation will also require operative approximation of the levators in many cases. Improvement cannot be expected to result from this procedure, however, unless the pelvic floor shows some residual resting activity. PMID- 8437505 TI - [Are there still indications for shunt operation in bleeding esophageal varices in the time of liver transplantation?]. PMID- 8437506 TI - Pharmacological characterization of the 5-hydroxytryptamine receptor coupled to adenylyl cyclase stimulation in human brain. AB - Recently, a 5-hydroxytryptamine (5-HT) receptor has been described, whose pharmacology was distinct from that of the already known serotonergic receptors, so that it has been called 5-HT4. Because the lack of a high affinity radioligand, the identification of this receptor depends entirely on functional pharmacological analysis. Its stimulation leads to an increase in cyclic AMP accumulation in mouse embryo colliculi neurons, in guinea pig hippocampus and in human heart. We studied the effect of two indoleamines, 5-HT and 5 methoxytryptamine (5-MeO-T), and a benzimidazolone derivative, BIMU 8, in stimulating basal adenylyl cyclase activity in human frontal cortex, and characterized the receptor subtype involved. In membranes prepared from this tissue, 5-HT, 5-MeO-T and BIMU 8 dose-dependently stimulated (13-25%) the basal enzyme activity (220 pmoles cyclic AMP/min/mg protein). 5-MeO-T behaved as a full agonist, BIMU 8 elicited about 60% of the maximal 5-HT effect. The selective 5 HT1A agonist 8-OH-DPAT, was devoid of any stimulating activity. ICS 205-930, a low affinity 5-HT4 receptor antagonist, completely reversed the effect of all three agonists at high concentrations. Therefore, the present data are consistent with the 5-HT-mediated stimulation of adenylyl cyclase in human frontal cortex resulting by the activation of a 5-HT4 receptor subtype. PMID- 8437507 TI - Functional integrity of hepatocyte canalicular membrane transport of taurocholate and bilirubin diglucuronide in Eisai hyperbilirubinuria rats. AB - Eisai hyperbilirubinuria rats (EHBR) are characterized by conjugated hyperbilirubinemia, and impaired or defective excretion of bilirubin, reduced glutathione and other organic anions from hepatocytes. Hepatocyte canalicular membrane vesicles (CMV) from EHBR and normal SD rats were studied with regard to taurocholate (TC) transport driven by ATP or a membrane potential and bicarbonate stimulated bilirubin diglucuronide (BDG) transport. ATP-dependent uptake or association of BDG with CMV was also studied in both strains of rats. No significant differences in the uptake of TC and BDG by CMV were observed. This indicates the functional integrity of the canalicular transporters for both organic anions in EHBR. Biliary excretion of taurolithocholic acid sulfate (TLCS) is defective in EHBR. However, TLCS inhibited ATP-dependent TC uptake by SD rat CMV competitively, which may be against the hypothesis that a common organic anion carrier is defective in canalicular membranes of jaundiced rats. PMID- 8437508 TI - Central interleukin-1 beta-induced inhibition of acid secretion in rats: specificity of action. AB - It is well established that IL-1 beta acts in the brain to potently inhibit gastric acid secretion in pylorus-ligated rats. The present study was designed to further investigate the specificity and mechanisms of the centrally mediated antisecretory action of IL-1 beta in conscious rats. Intracerebroventricular injection of IL-1 beta (100 ng) decreased acid secretion in pylorus-ligated rats and inhibited basal and pentagastrin-stimulated acid secretion in rats with chronic gastric fistula. The antisecretory effect of IL-1 beta (100 ng) injected into the lateral ventricle of pylorus ligated rats was completely reversed by prior intracerebroventricular injection of the IL-1 receptor antagonist, IL-1ra, (100 micrograms). Peripheral administration of the somatostatin monoclonal antibody, CURE.S6, did not modify intracisternal IL-1 beta-induced inhibition of acid secretion in pylorus ligated rats. IL-6 and tumor necrosis factor-alpha (100 ng) injected intracisternally did not influence gastric acid secretion in pylorus ligated rats. These data show that IL-1 beta action in the CNS is mediated through interaction with specific IL-1 receptors and is selective to this cytokine. IL-1 beta antisecretory action can be observed under basal and pentagastrin-stimulated conditions and is independent from somatostatin release in the periphery. PMID- 8437509 TI - Effect of serotonin axon injury on the somatostatinergic system in rat frontoparietal cortex. AB - In order to investigate the possibility that, in the rat, some cerebral cortex somatostatin (SS) receptors may be localized presynaptically on the terminals of serotonergic neurons, serotonin [5-hydroxytryptamine, (5-HT)] neurons in the central nervous system were damaged with a local intracerebral injection of the serotonergic neurotoxin, 5,7-dihydroxytryptamine(5,7-DHT). The injection of 5,7 DHT (11 micrograms free base dissolved in 10 microliters of isotonic saline containing 0.01% ascorbic acid) in rats produced an reduction by about 74% in frontoparietal cortical 5-HT content at 1 and 3 weeks after injection. These changes were associated with a significant decrease by about 30% in the total number of specific SS receptors in the frontoparietal cortex at both times studied without influencing the apparent affinity of the receptors. Together, these results suggest that a portion of the frontoparietal cortex SS receptors may be localized presynaptically on the serotonergic nerve terminals. The 5,7-DHT did not affect SS-like immunoreactivity (SSLI) levels suggesting that SS and 5-HT are not colocalized within the same neuronal elements in the rat frontoparietal cortex. PMID- 8437510 TI - Non-neuronal endogenous GABA efflux from the rat oviduct. AB - The subcellular distribution of Gamma-aminobutyric acid (GABA) was studied in the rat oviduct. The highest content of GABA was found in the soluble fraction. The effect of chemical stimulation of the endogenous GABA efflux from the rat oviduct was examined. High K+ concentrations could not induce elevation of the GABA efflux. Instead, a continuous spontaneous GABA efflux without change for long periods of time was observed. The total GABA content and GABA concentration were determined in the rat oviduct on days 1, 5, 10, 15, 30, 35 and 40 of the postnatal period and also during the estrous cycle. During postnatal development the GABA levels increase gradually with time reaching at prepuberal age a concentration similar to that found in diestrous rats. In the estrous cycle both GABA content and GABA concentration reached the highest value in the proestrous and the lowest value in the estrous phase. These findings support the hypothesis that GABA efflux may be modulated by the changes in oviductal fluid volume during the estrous cycle. PMID- 8437511 TI - Influence of clorgyline treatment on chronopharmacology of furosemide in rats. AB - Circadian variations in the adrenergic nervous system have been reported to be altered by chronic treatment with clorgyline, a monoamine-oxidase inhibitor. In the present study, the influence of clorgyline on the chronopharmacology of furosemide, a loop diuretic agent, was examined in rats maintained under conditions of light from 7 am to 7 pm and dark from 7 pm to 7 am. Clorgyline (4 mg/kg/day) or its vehicle alone was infused subcutaneously by osmotic minipumps for 14 days. Furosemide (30 mg/kg) was given orally at 12 am [noon (N)] or 12 pm [midnight (M)]. Urine was collected for 8 hours after the agent, and urinary excretions of sodium and furosemide were determined. Urine volume and urinary excretions of sodium and furosemide were significantly greater at 12 N than at 12 M in the vehicle-infused group of rats. However these administration time dependent changes in the effects of furosemide and its urinary excretion disappeared in the clorgyline-infused animals. These results suggest that the mode of the diurnal variation in the effects of furosemide is altered by chronic treatment with clorgyline. As chronic clorgyline is considered to disturb the adrenergic nervous system, the present findings are compatible with the hypothesis that this system is involved in the mechanism responsible for the time dependent change in the effects of furosemide. PMID- 8437512 TI - BQ-123, a peptidic endothelin ETA receptor antagonist, prevents the early cerebral vasospasm following subarachnoid hemorrhage after intracisternal but not intravenous injection. AB - The aim of this study was to evaluate the role of endothelin and endothelin ETA receptor in the early cerebral vasoconstriction following subarachnoid hemorrhage (SAH) in the rat. SAH induced by injection of autologous blood in the cisterna magna reduced by 22 to 38% cerebral blood flow (CBF) measured with radioactive microspheres at 30, 60 and 120 min after SAH. The cyclic pentapeptide BQ-123, a selective antagonist of the ETA receptor, injected intravenously (3 mg/kg) had no effect on this decrease in CBF. However, intracisternal BQ-123 (10 nmol) completely prevented the decrease in CBF at 60 and 120 min after SAH. These results suggest that BQ-123 does not cross the blood-brain barrier, but demonstrate that endothelin acting on ETA receptor plays a role in the pathogenesis of cerebral vasoconstriction in this rat model of SAH. PMID- 8437513 TI - Copper uptake and resistance in bacteria. AB - Copper ions are essential for bacteria but can cause a number of toxic cellular effects if levels of free ions are not controlled. Investigations of copper resistant bacteria have revealed several mechanisms, mostly plasmid-determined, that prevent cellular uptake of high levels of free copper ions. However, these studies have also revealed that bacteria apparently have efficient chromosomally encoded systems for uptake and management of trace levels of copper. This review will explore the relationship of copper uptake systems to resistance mechanisms and the possibility that copper resistance has evolved directly through modification of chromosomal copper uptake genes. PMID- 8437514 TI - Signal transduction between the two regulatory components involved in the regulation of the kdpABC operon in Escherichia coli: phosphorylation-dependent functioning of the positive regulator, KdpE. AB - The proteins KdpD and KdpE are crucial to the osmotic regulation of the kdpABC operon that is responsible for the high-affinity K+ ion transport system in Escherichia coli. We demonstrated previously that the response regulator, KdpE, is capable of undergoing phosphorylation mediated by the sensory protein kinase, KdpD. In this study, we obtained biochemical evidence supporting the view that when KdpE is phosphorylated, it takes on an active form that exhibits relatively high affinity for the kdpABC promoter, which in turn results in activation of the kdpABC operon. It was also suggested that the central hydrophobic domain of KdpD, which is conceivably responsible for membrane anchoring of this protein, plays a role in the signalling mechanism underlying KdpE phosphorylation in response to hyperosmotic stress. PMID- 8437515 TI - Identification and characterization of the exbB, exbD and tonB genes of Pseudomonas putida WCS358: their involvement in ferric-pseudobactin transport. AB - Catechol-cephalosporins are siderophore-like antibiotics which are taken up by cells of Pseudomonas putida WCS358 via the ferric-siderophore transport pathway. Mutants of strain WCS358 were isolated that are resistant to high concentrations of these antibiotics. These mutants failed to grow under iron-limiting conditions, and could not utilize different ferric-siderophores. The mutants fall in three complementation groups. The nucleotide sequence determination identified three contiguous open reading frames, which were homologous to the exbB, exbD and tonB genes of Escherichia coli respectively. The deduced amino acid sequence of P. putida ExbB showed 58.6% homology with its E. coli homologue, but, unlike the E. coli protein, it has a N-terminal extension of 91 amino acids. The ExbD proteins are 64.8% homologous, whereas the TonB proteins only show 27.7% homology. The P. putida exbB gene could complement an E. coli exbB mutation, but the TonB proteins were not interchangeable between the species. It is concluded that P. putida WCS358 contains an energy-coupling system between the membranes, for active transport across the outer membrane, which is comprised of a TonB-like energy-transducing protein and two accessory proteins. This system is similar to, but not completely compatible with, the E. coli system. PMID- 8437516 TI - Involvement of lipopolysaccharide in the secretion of Escherichia coli alpha haemolysin and Erwinia chrysanthemi proteases. AB - The presence of the alpha-haemolysin secretion genes sensitizes Escherichia coli to vancomycin, a glycopeptide antibiotic that is normally excluded from the Gram negative envelope (owing to its large size) (M(r) 1400). The selection of vancomycin mutants in strains carrying such genes was found to be a very powerful method for selecting non-haemolytic mutants. In this way, mutations in the known secretion genes, hlyB, hlyD and tolC, were obtained. However additional mutations mapped in genes rfaH and galU which are required for lipopolysaccharide (LPS) biosynthesis. Mutations in rfaH and galU strongly reduced alpha-haemolysin secretion as well as the secretion of Erwinia chrysanthemi proteases in E. coli without affecting their synthesis. These mutations markedly lowered the content of TolC protein, required for haemolysin secretion and also of the PrtF protein necessary for protease secretion. These results raise the possibility that LPS is involved in the correct incorporation of the TolC and PrtF proteins into the cell envelope. PMID- 8437517 TI - Definition of nitrite and nitrate response elements at the anaerobically inducible Escherichia coli nirB promoter: interactions between FNR and NarL. AB - Transcription initiation at the Escherichia coli nirB promoter is induced by anaerobic growth and further increased by the presence of nitrite or nitrate in the growth medium. Expression from this promoter is totally dependent on the transcription factor, FNR, which binds between positions -52 and -30 upstream of the transcription startsite. The 20 base pairs from position -79 to -60 contain an inverted repeat of two 10-base sequence elements that are related to sequences at the NarL-binding site at the E. coli narG promoter. Comparison of these, and sequence elements at other promoters regulated by NarL, suggests a consensus NarL binding sequence. Mutations in the putative NarL-binding site at the nirB promoter decrease FNR-dependent anaerobic induction, suggesting that NarL acts as a helper to FNR during transcription activation. These mutations also suppress induction by nitrite: single mutations at symmetry-related positions have similar effects, whilst double mutations have more severe effects, probably because two NarL subunits bind to the inverted repeat. Disruption of narL decreases nitrite induction of the nirB promoter whilst not suppressing induction by nitrate, suggesting that there may be a second nitrate-responsive factor. Nitrate induction was, however, suppressed by double mutations at symmetry-related positions in the NarL-binding site, suggesting that this putative second factor may bind to sequences similar to those recognized by NarL. PMID- 8437518 TI - Membrane topology of MalG, an inner membrane protein from the maltose transport system of Escherichia coli. AB - In Escherichia coli, the binding protein-dependent transport system for maltose and maltodextrins is composed of five proteins--LamB, MalE, MalF, MalG and MalK- located in the three layers of the bacterial envelope. Proteins MalF and MalG are hydrophobic inner membrane components mediating the energy-dependent translocation of substrates into the cytoplasm. In this paper, we analyse the topology of the MalG protein by using methods based on the properties of fusions between malG and 'phoA, a truncated gene encoding alkaline phosphatase lacking its translation initiation and exportation signals. Fusions were obtained by using either phage lambda TnphoA or by constructing in vitro fusions located randomly within the malG gene. The deduced topological model suggests that MalG spans the membrane six times and has its amino- and carboxy-termini in the cytoplasm. These results will be helpful for the interpretation of the phenotypes of mutants in malG. PMID- 8437519 TI - Sequence-function relationships in MalG, an inner membrane protein from the maltose transport system in Escherichia coli. AB - The malG gene encodes a hydrophobic cytoplasmic membrane protein which is required for the energy-dependent transport of maltose and maltodextrins in Escherichia coli. The MalG protein, together with MalF and MalK proteins, forms a multimeric complex in the membrane consisting of two MalK subunits for each MalF and MalG subunit. Fifteen mutations have been isolated in malG by random linker insertion mutagenesis. Two regions essential for maltose transport have been identified. In particular, a hydrophilic region containing the peptidic motif EAA --G---------I-LP, highly conserved among inner membrane proteins from binding protein-dependent transport systems, is essential for maltose transport. The results also show that several regions of MalG are not essential for function. A region (residues 30-50) encompassing the first predicted transmembrane segment and the first periplasmic loop in MalG may be modified extensively with little effect on maltose transport and no effect on the stability and the localization of the protein. A region located at the middle of the protein (residues 153-157) is not essential for the function of the protein. A region, essential for maltodextrin utilization but not for maltose transport, has been identified near the C-terminus of the protein. PMID- 8437520 TI - MxiD, an outer membrane protein necessary for the secretion of the Shigella flexneri lpa invasins. AB - The invasive phenotype of Shigella flexneri is conferred by a 220 kb virulence plasmid, pWR100, that encodes both the lpa proteins, which are involved in the entry process, and factors which are required for the export and correct localization of the lpa proteins. We have characterized the mxiD gene, whose expression, like that of the ipa operon, is regulated by temperature. After inactivation of mxiD, the mutant strain was unable to invade HeLa cells and to provoke keratoconjunctivitis in guinea-pigs. Analysis of culture supernatants indicated that wild-type S. flexneri secretes about nine polypeptides and that secretion of several of these, including lpaA, lpaB, and lpaC, is abolished in the mxiD mutant. Examination of the membrane proteins of the wild-type and mxiD strains suggested that MxiD is an outer membrane protein. Amino acid sequence comparison revealed that MxiD is homologous to the YscC protein of Yersinia enterocolitica and to the C-terminal region of the PulD protein of Klebsiella pneumoniae. Both YscC and PulD are involved in extracellular protein secretion. These results indicate that MxiD is an essential component of the lpa secretion apparatus. PMID- 8437522 TI - Patient education videos an excellent way to inform patients, avoid lawsuits. They're also a great image-builder. PMID- 8437521 TI - C-terminal truncation of the transcriptional activator encoded by areA in Aspergillus nidulans results in both loss-of-function and gain-of-function phenotypes. AB - Mutations truncating as many as 143 C-terminal residues from the transcriptional activator encoded by the areA gene, mediating nitrogen metabolite repression in Aspergillus nidulans, do not significantly reduce the ability of the areA product to activate expression of most genes under areA control. Such mutations can even have a gain-of-function, derepressed phenotype, consistent with a critical role for this region in modulating the activity of the areA protein. However, expression of a few genes under areA control is substantially impaired by such C terminal truncations, indicating that regions of an activator protein can play differing roles in the control of different structural genes. This underlines the advantages of being able to monitor effects of areA mutations on expression of large numbers of structural genes. Additionally, it is shown that truncation of as many as 153 C-terminal residues, virtually all amino acids C-terminal to the DNA-binding region, is compatible with retention of some areA function. PMID- 8437523 TI - Legislative ban on assisted suicide: impact on Michigan's medical practice. PMID- 8437524 TI - Now it's PHOs. New physician hospital organizations offer flexible, effective structural alternative. PMID- 8437525 TI - Parkinson's disease: another treatment tool. The Michigan Parkinson Foundation. PMID- 8437526 TI - [Long-term follow-up of anti-tachycardia surgery in patients with ventricular tachycardia]. AB - From March 1980 to May 1992 mapping guided surgery was performed in 132 patients with drug-refractory recurrent ventricular tachycardia. There were 121 patients (group I) with coronary disease and 11 patients (group II) had noncoronary ventricular tachycardia. Patients in group I underwent subendocardial resection and cryoablation was performed in group II patients. Perioperative mortality (< 30 days after surgery) was 8% (10/132 patients). During the mean follow-up of 41 +/- 24 months, 37/122 patients (30%) died, 35/111 patients in group I (32%) and 2/11 patients in group II (18%) (p = 0.29). In group I, sudden death occurred in 8/111 patients (7%) and cardiac death in 23/111 patients (21%); in group II, 1/11 patients (9%) died from sudden and 1/11 patients (9%) from cardiac death. Nonfatal recurrences occurred significantly more frequently in group II (6/11 patients, 55%) than in group I (16/111 patients, 14%) (p < 0.01). During the follow-up functional class of heart failure improved in 69 patients (57%), remained constant in 27 patients (22%) and decreased in the remaining 26 patients (21%). The surgical approach to control ventricular tachycardia has low rates of sudden death and nonfatal recurrences in patients with drug-refractory ischemic ventricular tachycardia. Patients with noncoronary disease had a high incidence of nonfatal ventricular tachycardia after surgery and should be considered for other therapeutic approaches in the future. PMID- 8437527 TI - [Sulbactam/ampicillin in comparison with cefuroxime for infections of the lower respiratory tract. Results of a prospective, randomized comparative study]. AB - In a randomized prospective study, ampicillin (AMP) in combination with the beta lactamase-inhibitor, sulbactam (SBT) was compared with cefuroxime (CXM) in 73 hospitalized patients with lower respiratory tract infections. 36 patients received SBT/AMP 1 g/2 g t.i.d. and 37 patients received CXM 1.5 g t.i.d.--both in the form of i.v. infusion. The duration of treatment ranged from five to twelve days, with a median of eight days in each group. 23 patients (64%) of the SBT/AMP group had pneumonia, while 13 (36%) had acute purulent bronchitis; 13 of the patients (36%) received artificial respiration. 23 patients (62%) of the CXM group had pneumonia and 14 (38%) acute purulent bronchitis; eight patients (22%) required artificial respiration. In 54 patients (SBT/AMP: 26; CXM: 28) initial culture yielded bacterial pathogens, mainly Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, Staphylococcus aureus and pneumococci. 35 patients in each group were clinically evaluable. 31 patients (89%) responded to treatment with SBT/AMP, and 28 patients (80%) to treatment with CXM. Four patients (11%) who received SBT/AMP failed to respond, as did seven patients on CXM. The bacteriological efficacy was assessed in 26 patients of the SBT/AMP group: in 22 cases (84%) baseline pathogens were eradicated, while in two patients (8%) each, there was persistent infection and a superinfection, respectively. In 23 patients (82%) of the CXM group (28 patients evaluated) the pathogens were eradicated, while three cases (11%) had persistent infection, and two (7%) superinfection. Apart from a case of exanthema under CXM, no adverse drug reactions were reported. No statistically significant differences were to be seen between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437528 TI - [Molsidomine in chronic heart failure with liver congestion--oral or intravenous therapy?]. AB - Patients suffering from congestive heart failure combined with gastrointestinal congestion often present irregular resorption and metabolism of orally applicated cardiovascular drugs. Intravenous therapy therefore is used very often for those patients. In this trial we compared the efficiency of molsidomine given either orally or intravenously in patients suffering from congestive heart failure. We investigated ten patients (54.6 +/- 13 years) with congestive heart failure (NYHA III and IV) and a central venous pressure > 10 mmHg. Five patients of group A were given 4 mg of molsidomine intravenously on the first day and an oral dose of 4 mg of molsidomine on the second day. The five patients of group B received the oral dose on the first day and intravenous treatment on the second day. Central venous pressure and plasma levels of molsidomine and of the effective metabolite SIN-1 were measured before as well as ten, 20, 40, 60 minutes, two, four and eight hours after application of molsidomine. Central venous pressure decreased significantly up to two hours after molsidomine in both oral and intravenous groups (p < or = 0.01). There was no relevant difference between the oral and the intravenous group. The hemodynamic parameters correlated with molsidomine plasma levels. According to our results the efficiency of oral molsidomine does not differ from intravenous molsidomine in patients with congestive heart failure. PMID- 8437529 TI - [A rare source of hemorrhage in the stomach (Dieulafoy vascular abnormality)]. PMID- 8437530 TI - [Respect for the body or fear of medicine]. PMID- 8437531 TI - [Therapy of severe AIDS-associated diarrhea with the somatostatin analog octreotide]. PMID- 8437532 TI - [Backache and osteoporosis in perimenopausal women]. AB - Osteoporosis is thought to represent one of the main causes of back pain in perimenopausal women. One hundred perimenopausal women (45 to 60 years) who were consecutively admitted in order to clarify the cause of their back pain were examined. In 20% disc degenerations were found. Other degenerative disorders (osteoarthritis) of the spine without coincident scoliosis were found to be the second most common cause of pain in 19%. Scoliosis due to different leg length was detected in 15%, idiopathic scoliosis in 13%. Spondylolisthesis occurred in 7% even more frequently than osteoporosis with vertebral deformities in 6%. Non osteoporotic vertebral deformities were seen as often as osteoporotic ones. Rare diagnoses among others were seronegative spondyloarthropathy and fibrositis. Our results indicate that back pain in women up to 60 years is mostly due to degenerative disorders of the spine. Osteoporosis with vertebral deformities as cause of pain is quite rare. Comparing bone mineral density of the distal forearm (SPA) of the patients with back pain not due to manifest osteoporosis (98 +/- 15% of age related mean) with those of 50 asymptomatic women (96 +/- 14%) and 50 female patients with pain in other regions of the skeleton (103 +/- 17%) in the same age group, there was no evidence for any relation between low bone mineral density and skeletal pain. PMID- 8437533 TI - [Glucocorticoids in treatment of chronic inflammatory bowel diseases]. PMID- 8437534 TI - [Glucocorticoids in rheumatology]. PMID- 8437535 TI - [Basic principles of glucocorticoid therapy]. PMID- 8437536 TI - [Fluocortolone--a classical and modern glucocorticoid]. PMID- 8437537 TI - [Glucocorticoids in interstitial lung diseases]. PMID- 8437538 TI - [Glucocorticoids in obstructive respiratory tract diseases]. PMID- 8437539 TI - [Current problems of glucocorticoid therapy in neurology]. PMID- 8437540 TI - Minors' access to tobacco--Missouri, 1992, and Texas, 1993. AB - Approximately 75% of adults who have regularly smoked cigarettes tried their first cigarette before their 18th birthday, and about half became regular smokers by age 18 years. Despite the importance of reducing smoking among adolescents, the prevalence of smoking among high school seniors has not decreased substantially from 1981 through 1991. National health objectives for the year 2000 have targeted substantial reductions in smoking among persons aged < 20 years, and reducing access to cigarettes through laws or statutes is an important strategy in reaching this goal. This report describes the results of efforts in two states--Missouri and Texas--to characterize access of minors to cigarettes and other tobacco products. PMID- 8437541 TI - Injuries to international petroleum drilling workers, 1988-1990. AB - Occupationally related death rates among workers involved in oil and gas extraction activities have been higher than rates for workers from all U.S. industries combined. In 1991, nonfatal work-related injury (NFI) rates for workers in the U.S. oil and gas field service industry (standard industrial classification [SIC] codes 138.1, 138.2, and 138.9)* were 49% greater than rates for all workers in private industry and tended to be more severe, with a lost workdays rate more than 2.8-fold higher than in private industry as a whole. To develop improved strategies for preventing fatal injuries (FIs) and NFIs among petroleum drilling workers, the Louisiana Office of Public Health (LOPH) analyzed data on injury-related incidents in the petroleum drilling industry during 1988 1990. This report summarizes the results of this study. PMID- 8437542 TI - Update: influenza activity--United States, 1992-93 season. AB - From September 27, 1992, through February 13, 1993, the World Health Organization collaborating laboratories in the United States reported 1042 influenza virus isolates. For the weeks ending December 5, 1992, through February 6, 1993, the ratio of specimens positive for influenza virus to total specimens submitted for respiratory virus testing increased from 0.02 to 0.2. PMID- 8437543 TI - Health status of Haitian migrants--U.S. Naval Base, Guantanamo Bay, Cuba, November 1991-April 1992. AB - In November 1991, following a military coup in Haiti, thousands of Haitians fled that country in small open boats. Most migrants were intercepted by U.S. Coast Guard cutters and taken to the U.S. Naval Base at Guantanamo Bay (GTMO), Cuba (Figure 1), where the U.S. Department of Defense (DOD) established a joint task force (JTF) migrant relief operation.* This report summarizes the results of health assessments of migrants conducted by the JTF. PMID- 8437544 TI - Impact of new legislation on needle and syringe purchase and possession- Connecticut, 1992. AB - Human immunodeficiency virus (HIV) and other bloodborne pathogens are transmitted among injecting-drug users (IDUs) through the reuse and sharing of contaminated needles and syringes (NSs). Of the 689 acquired immunodeficiency syndrome (AIDS) cases reported in Connecticut in 1992, 413 (60%) were associated with injecting drug use. To help reduce IDUs' use of contaminated NSs, Connecticut enacted laws effective July 1, 1992, that allow the purchase without a prescription of up to 10 NSs at one time in pharmacies and the possession of up to 10 clean NSs. Before this date, purchase and possession of NSs without a prescription had been illegal in Connecticut. This report presents preliminary information from the first 5 months of an ongoing evaluation to determine whether the new laws affected pharmacy-based NS sales, IDUs' reported knowledge of the laws and places to obtain NSs, and law enforcement officers' risk for needlestick injuries. PMID- 8437545 TI - Tetanus fatality--Ohio, 1991. AB - In August 1991, the Ohio Department of Health received a report of a fatal case of tetanus. This report summarizes the investigation of this case. PMID- 8437546 TI - Comparison of early and late latent syphilis--Colorado, 1991. AB - Latent syphilis (i.e., the presence of serological evidence for syphilis without clinical manifestations) is divided into early latent ([EL] less than 1-year's duration) and late latent ([LL] more than 1-year's duration) stages (1). LL syphilis, which is often associated with low nontreponemal test (e.g., rapid plasma reagin [RPR]) titers and is presumed to have been acquired in the distant past, is not routinely included in syphilis surveillance reports and analyses. Although a separate classification of "unknown latent syphilis" has been proposed (1), in practice, duration is unknown for nearly all syphilis cases that are classified as LL. This report compares EL and LL syphilis cases in Colorado during 1991 and demonstrates substantial overlap in their characteristics. PMID- 8437547 TI - Recommendations for HIV testing services for inpatients and outpatients in acute care hospital settings. PMID- 8437548 TI - [Study of metabolic dynamics under severe surgical stress--investigation by the method of respiratory gas analysis]. AB - To elucidate quantitative analysis of the hypermetabolic status and classification of energy substrates kinetics, the metabolic dynamics after radical operation for thoracic esophageal cancer was investigated in 10 patients primarily by the method of respiratory gas analysis. 1) REE showed almost 30 kcal/kg/day and no significant change on each postoperative day. Energy intake in addition to surgical stress influenced the metabolic dynamics (specific dynamic action: SDA). So authors originally devised a postoperative metabolic index "PMI" in consideration for the effect of SDA. PMI is defined; PMI = (REE kcal/day-BEE kcal/day)/Energy Intake (non-protein kcal/day). according to PMI, it was clarified that the hypermetabolic status reached a maximum value on the first postoperative day, showed a steep decrease up to the 3rd postoperative day and afterwards slow recovery. PMI revealed a significant correlation (r = 0.792, p < 0.001) with daily urinary epinephrine excretion in the immediate postoperative period (up to the 3rd day). These results suggest PMI might be useful in the quantitative evaluation of the hypermetabolic status under surgical stress. 2) Energy substrates kinetics was clearly classified into six patterns according to three parameters such as energy balance, glucose balance, and predominant fat metabolism (fat oxidation or synthesis). PMID- 8437549 TI - [Effect of dopamine on cardiac performance in an early postburn period]. AB - To clarify the effects of dopamine on cardiac performance in an early postburn period, left ventricular (LV) end-systolic pressure--volume relations (ESPVR) and stroke work--end-diastolic volume relations (PRSW) were studied in full thickness and 50% body surface area burns in anesthetized dogs during six hour postburn period. The dogs (16-28 kg) were divided into two groups; a fluid resuscitated groups (n = 7) and a fluid and dopamine resuscitated group (n = 6). The ESPVR and PRSW were derived from pressure--volume loops produced by vena caval occlusion. In the dopamine group, peak systolic pressure rose and cardiac output and contractility tended to increase in comparison with burned group. The ESPVR had also tended to shift right side. We concluded that under sufficient fluid resuscitation low-dose dopamine may be effective to improve the cardiac performance and peripheral circulation in an early postburn period. PMID- 8437550 TI - [Preoperative immunotherapy in patients with gastric cancer--with special reference to analysis with monoclonal antibodies of T-lymphocyte subsets and interleukin-2 oral administration of OK-432 (Picibanil)]. AB - The effects of oral administration of OK-432 on immune reactivities of gut associated lymphoid tissue (GALT) were studied in patients with gastric cancer. The lymphocytes of peripheral blood, regional lymph nodes and spleen in patients with gastric cancer were measured by using different monoclonal antibodies and flow cytometry. OKT3, OKT4, OKT8, OKM1, OKT4+2H4+, OKT4+2H4-, OKT8+Leu15+ and OKT8+1Leu5- were used as monoclonal antibodies. The NK activity, Interleukin-2 production and Interleukin-2 receptor were also measured. After oral administration of OK432, 1) little change was found in peripheral blood and spleen, 2) the percentages of OKT3, OKT4, OKT4+2H4- and the ratio of OKT4/OKT8 were increased in proximal regional lymph nodes, and 3) the percentages of OKT8 and OKT8+Leu15- in regional lymph nodes were not changed. These results suggest that the helper T cell activity and the antitumor immunity of regional lymph nodes were elevated by oral administration of OK-432. PMID- 8437551 TI - [Clinical study on the cell kinetics of gastric cancer using bromodeoxyuridine labeling index--its relations with DNA ploidy pattern and epidermal growth factor]. AB - Forty fresh gastric cancer specimens were examined by immunohistological staining using anti-BrdU monoclonal antibody, and simultaneously the specimens were studied by DNA ploidy pattern, EGF with flowcytometer and the immunohistological staining. For EGF study, the same 40 gastric cancer formalin fixed specimens were used. The results of flowcytometric measurement were divided into diploid and aneuploid patterns. BrdU positive stained cancer cells were observed in growing border area than in the center of tumor, and histologically in P(+), n(+), ps(+), INF gamma, and in scirrhous type, deep spread type and advanced stage. This data suggested that the BrdU labeling index seemed to be related to invasion, proliferation, and metastasis of cancer cells. However the positive rates of EGF were higher in ps(+), deep spread type and BrdU positive type but not in P(+), n(+), and EGF was considered to related to invasion but not to be related to metastasis. Although aneuploid pattern cancer showed high BrdU labeling index in ps(+), diploid pattern didn't indicate such tendency. High BrdU positive rate aneuploid cancer were seemed to grow quickly, advance in short period and own worse character. Further investigation would be necessary. PMID- 8437553 TI - [An experimental study on the induction of anti-tumor immunological activity after cryosurgery for liver carcinoma, and the effect of concomitant immunotherapy with OK432]. AB - Cryosurgery on liver carcinoma (MRMT-1) in rats and pre-operative administration of OK432 were performed in order to study host immunological response and the effect of immunotherapy before cryosurgery, respectively. Rats were divided into five groups, by treatment given: control, false-operative, incomplete-frozen, complete-frozen and complete-frozen + OK432-administrated groups under several conditions. In the incomplete-frozen group, the survival days significantly prolonged as compared with controls. Phytohemagglutinin (PHA) blast formation and CD4 positivity exhibited high levels at 8 weeks after cryosurgery. In the complete-frozen group, survival time was not prolonged and 3 cases of early death were observed. Moreover, CD4 positivity decreased at 3 days and CD8 positivity increased at 2 weeks after cryosurgery, significantly. On the other hand, in the complete-frozen + OK432-administrated group, CD4 positivity decreased gradually after cryosurgery. In contrast, PHA blast formation was significantly high at 8 weeks and the rise of CD8 positivity in the complete-frozen group was significantly suppressed with OK432 to a value of 31.8 +/- 4.1%. In addition, the survival time showed a prolonging tendency, with the exception of 2 cases of early death. From these results, we concluded that immunological response after cryosurgery for liver carcinoma may be induced by changes in cell immunity, and it was suggested that combination therapy with cryosurgery and preoperative immunotherapy might be effective. PMID- 8437552 TI - [Effect of intra-venous hyperalimentation on hepatic energy metabolism after hepatic resection in the cirrhotic rat]. AB - We evaluated experimentally the effect of administration of glucose on hepatic energy metabolism, mitochondrial functions and lipid metabolism after hepatic resection. The 75% hepatic resection was performed on thioacetamide induced cirrhotic rat. Glucose solution with 30 Cal/kg/day (group I) or 200 Cal/kg/day (group II) was administrated intravenously for 48 hours after hepatic resection. Blood levels of ketone bodies and glucagon, tissue activities of ATP synthesis and tissue content of adenine nucleotides were measured in both groups. Hepatic energy charge was significantly decreased in group II, comparing with group I. When fatty acid was used as a substrate for respiratory system, the activity of ATP synthesis on mitochondria after hepatic resection rose, while in case pyruvate was used as a substrate the value was declined. On the levels of serum free fatty acids and ketone bodies, there were no remarkable changes in group I, while in group II, obvious declines were investigated. It is suggested that the overload of glucose in the early stage after hepatic resection is unfavorable to hepatic energy metabolism because of decline of serum free fatty acid by hyperinsulinemia and suppression of fatty acid oxidation by decline of blood glucagon. PMID- 8437554 TI - [The inhibitory effect of nafamostat mesilate (FUT-175) on liver metastasis]. AB - Basic investigation of inhibitory effect on metastasis of nafamostat mesilate (FUT-175) which is a kind of serine protease inhibitors, was performed. Colon 26 cells were injected to the portal vein of CDF1 mice. FUT-175 at doses of 0.3, 1.0, 3.0, 10.0 mg/kg was injected intravenously every 7 day. Mice were sacrificed on day 21, and metastasis of liver surface were measured. The dose dependent reduction of metastasis was observed and reduction of metastasis of mice treated at a dose of 10.0 mg/kg was significant. FUT-175 showed no cytotoxicity at doses of 10(-5) M or less in vitro, and blood concentration of mice, treated at a dose of 10.0 mg/kg, was 2.67 x 10(-7) M. The results showed that inhibitory effect of FUT-175 on metastasis was not caused by direct cytotoxicity. FUT-175 at 2.67 x 10(-7) M in vitro can inhibit only thrombin and plasmin at nearly 50%, and can not inhibit platelet aggregation and collagenase directly. Possible mechanism of inhibition of metastasis is that FUT-175 inhibited both thrombin-mediated platelet aggregation and plasmin-mediated collagenase activation, that arrest and extravasation in cancer cells were inhibited. If protease inhibitor is administered continuously and immediately after surgery, liver metastasis may be prevented. PMID- 8437555 TI - [Endoscopic sphincteroplasty (not sphincterotomy) using the clips--a preliminary report]. AB - Reports exist that incomplete division of the papilla by endoscopic sphincterotomy may lead to restenosis, cholangitis, and stone recurrence. In view of evolution of surgical sphincterotomy to sphincteroplasty, we studied feasibility of endoscopic sphincteroplasty. In 36 dogs, at laparatomy, the papilla was divided using a diathermy sphincterotome to create retroperitoneal perforation. Twelve dogs underwent approximation of the bile duct and duodenal walls with silk sutures. Another 12 dogs had the walls approximated with clips using an endoscopic clip appliance. The other 12 dogs had no approximation. Blood chemistry was obtained before and serially after surgery. Duodenobiliary barium regurgitation was determined in 2-3 weeks. Four dogs each in each group were sacrificed at 1, 2, and 4 weeks to examine the papilla macro- and microscopically. In regard to hemostasis and prevention of leakage, the effect of the clips was similar to the sutures, resulting in a wide opening with free regurgitation. The no treatment group had persistent abnormal liver function tests and amylase levels. Three dogs died on leakage with abscess and the other nine had stenosis of the papilla. These data suggest that endoscopic sphincteroplasty may be feasible using the clips. A first clinical case where the clips were used to obtain a wide opening which passed a 15-mm balloon is briefly described. PMID- 8437556 TI - [Study on proliferating potential by Ag-NORs staining in human pancreatic carcinoma]. AB - NORs (Nucleolar Organizer Regions) are loops of DNA encoding ribosomal RNA, which reflect cellular activity. The Ag-NORs staining was applied to paraffin sections of 10 normal pancreas, 10 chronic pancreatitis and 23 pancreatic cancer, with 17 gastric and 18 colonic cancers. We calculated the mean Ag-NORs number and Ag-NORs index, and defined T/N ratio. The mean Ag-NORs number was compared with the data obtained by Flow cytometry (FCM) in pancreatic carcinoma. A significant difference in Ag-NORs index was found between benign (normal: 1.86 +/- 0.38, pancreatitis: 2.14 +/- 0.53) and malignant tissues (4.02 +/- 1.19) of the pancreas (p < 0.01). Compared with the data by FCM, there was a significant correlation between the mean Ag-NORs number and the percentage of S-phase cells in pancreatic carcinoma (r = 0.59, p < 0.01). Ag-NORs index in pancreatic carcinoma showed significantly lower value than that in cancer of stomach (6.35 +/- 1.32) and colon (7.66 +/- 1.35), but there was no difference in T/N ratio among them. In conclusion, the Ag-NORs staining is useful for analyzing proliferating activity in pancreatic carcinoma. The proliferating potential in pancreatic carcinoma is lower than that in gastric and colonic ones. This may be due to the low proliferating potential of the background mucosa from which pancreatic carcinoma will arise. PMID- 8437557 TI - [Pigment gallstone formation in canines after total colectomy: preliminary report]. PMID- 8437558 TI - [Localization of the F(ab')2 fragment of monoclonal antibody A7 in pancreatic cancer: preliminary report]. PMID- 8437559 TI - Correlation between the size of the intergenic regulatory region, the status of cytosine methylation of rRNA genes and nucleolar expression in wheat. AB - A large number of wheat rRNA genes are methylated at all the CCGG sites that are present in the intergenic regions. A smaller number of rRNA genes are not methylated at one or more CCGG sites. A subset of genes was found unmethylated at a specific CCGG site just downstream of the array of 135 bp A repeats in the intergenic region. In all the genotypes studied, the rDNA loci with larger intergenic regions between their genes also possess a greater number of rRNA genes that are unmethylated at one or more CCGG sites in the intergenic regions than do the loci with shorter intergenic regions. In four genotypes (for which data were available), rDNA loci with longer intergenic regions had larger secondary constrictions on metaphase chromosomes, a measure of relative locus activity, than the loci with shorter intergenic regions. The results have been integrated into a model for the control of rDNA expression based on correlations between cytosine methylation patterns and the number of upstream 135 bp repeats in intergenic regions. According to this model the 135 bp repeats play a part in the control of gene activity by binding a protein(s) that is in limiting supply, thereby predisposing the neighbouring gene to become active preferentially. PMID- 8437560 TI - Subcellular location of lincomycin resistance in Nicotiana mutants. AB - Lincomycin-resistant Nicotiana plumbaginifolia plastid mutants were considered also to carry mitochondrial mutations on the basis of their ability to grow in the dark under selective conditions. To clarify the role of mitochondria, individual protoplasts of the green, lincomycin-resistant N. plumbaginifolia mutant LR400 were microfused with protoplasts of the N. tabacum plastid albino line 92V37, which possesses N. undulata cytoplasm. the production of lincomycin resistant albino cybrid lines, with N. undulata plastids and recombinant mitochondria, strongly indicated a determining role for mitochondria in the lincomycin resistance. Sequence analysis of the region encompassing putative mutation sites in the 26S rRNA genes from the LR400 and several other lincomycin resistant N. plumbaginifolia mutants revealed, however, no differences from the wild-type sequence. As an alternative source of the resistance of the fusion products, the N. tabacum fusion partner was also taken into account. Surprisingly, a natural lincomycin resistance of tobacco was detected, which was inherited as a dominant nuclear trait. This result compromises the interpretation of the fusion data suggested above. Thus, to answer the original question definitively, the mutant LR400 was crossed as a female parent with a N. plumbaginifolia line carrying streptomycin-resistant N. tabacum plastids. Calli were then induced from the seedlings. Occasional paternal plastid transmissions were selected as streptomycin-resistant calli on selective medium. These cell lines were shown by restriction enzyme analysis to contain paternal plastids and maternal mitochondria. They were tested for greening and growing ability in the presence of lincomycin. These resistance traits proved to be genetically linked and exclusively located in the plastids. PMID- 8437561 TI - Autoregulatory expression of the Escherichia coli hns gene encoding a nucleoid protein: H-NS functions as a repressor of its own transcription. AB - The Escherichia coli nucleoid protein, H-NS (or H1a), appears to influence the regulation of a variety of unrelated E. coli genes and operons. To gain an insight into the regulation of the hns gene itself, we constructed in this study a hns-lacZ transcriptional fusion gene and inserted a single copy at the att lambda locus on the E. coli chromosome. Expression of hns transcription appeared to be moderately regulated in a growth phase-dependent manner. It also emerged that hns transcription is under negative autoregulation, at least in the logarithmic growth phase. The results of in vitro transcription experiments confirmed that H-NS functions as a repressor for its own transcription. Thus, H NS was shown to exhibit relatively high affinity for the DNA sequence encompassing the hns promoter region, as compared with a non-specific sequence. These results support the view that the nucleoid protein, H-NS, can function as a transcriptional regulator. PMID- 8437562 TI - Promoter sequences of a potato pathogenesis-related gene mediate transcriptional activation selectively upon fungal infection. AB - Transcription of at least one member of the potato prp1 gene family, prp1-1, is activated at early stages of potato infection with the late blight fungus Phytophthora infestans. In this paper we present evidence that mRNA encoded by prp1-1 does not accumulate in response to abiotic environmental cues which stimulate transcription of other defence-related genes. Regulatory elements were identified in the 5' terminal region of prp1-1 by assaying the expression pattern of chimeric promoter/beta-glucuronidase gene constructs in transgenic potato. A 273 bp fragment comprising the promoter sequence between positions -402 and -130 was sufficient for rapid and strictly localized transcriptional activation at infection sites during the development of late blight disease. Like the native promoter, this truncated promoter did not mediate transcriptional activation in response to other abiotic stimuli. The use of the identified regulatory region to generate conditional mutations selectively at infection sites is discussed. PMID- 8437563 TI - LamB as a carrier molecule for the functional exposition of IgG-binding domains of the Staphylococcus aureus protein A at the surface of Escherichia coli K12. AB - One, two or four IgG-binding domains of the Staphylococcus aureus Protein A (SPA) were inserted into the LamB protein which was expressed under control of the tac promoter. The chimeric proteins were shown to be exposed at the cell surface by analysis of isolated outer membranes and also by testing their functional interaction with IgG molecules. We hereby show that the LamB protein can accept as many as 232 amino acids (four SPA domains) and still be incorporated into the Escherichia coli outer membrane, while maintaining the functional conformation of the inserted SPA polypeptides. PMID- 8437564 TI - Identification and characterization of a gene cluster involved in nitrate transport in the cyanobacterium Synechococcus sp. PCC7942. AB - The nrtA gene, which has been proposed to be involved in nitrate transport of Synechococcus sp. PCC7942 (Anacystis nidulans R2), was mapped at 3.9 kb upstream of the nitrate reductase gene, narB. Three closely linked genes (designated nrtB, nrtC, and nrtD), which encode proteins of 279, 659, and 274 amino acids, respectively, were found between the nrtA and narB genes. NrtB is a hydrophobic protein having structural similarity to the integral membrane components of bacterial transport systems that are dependent on periplasmic substrate-binding proteins. The N-terminal portion of NrtC (amino acid residues 1-254) and NrtD are 58% identical to each other in their amino acid sequences, and resemble the ATP binding components of binding protein-dependent transport systems. The C-terminal portion of NrtC is 30% identical to NrtA. Mutants constructed by interrupting each of nrtB and nrtC were unable to grow on nitrate, and the nrtD mutant required high concentration of nitrate for growth. The rate of nitrate-dependent O2 evolution (photosynthetic O2 evolution coupled to nitrate reduction) in wild type cells measured in the presence of L-methionine D,L-sulfoximine and glycolaldehyde showed a dual-phase relationship with nitrate concentration. It followed saturation kinetics up to 10 mM nitrate (the concentration required for half-saturation = 1 microM), and the reaction rate then increased above the saturation level of the first phase as the nitrate concentration increased. The high-affinity phase of nitrate-dependent O2 evolution was absent in the nrtD mutant. The results suggest that there are two independent mechanisms of nitrate uptake and that the nrtB-nrtC-nrtD cluster encodes a high-affinity nitrate transport system. PMID- 8437565 TI - Cloning and expression of distinct nitrite reductases in tobacco leaves and roots. AB - Three tobacco nitrite reductase (NiR) cDNA clones were isolated using spinach NiR cDNA as a probe. Sequence analysis and Southern blot hybridization revealed four genes in tobacco. Two of these genes presumably derived from the ancestral species Nicotiana tomentosiformis, the other two from the ancestor N. sylvestris. Northern blot analysis showed that one gene from each ancestral genome was expressed predominantly in leaves, whilst RNA from the other was detected mostly in roots. The accumulation of both leaf and root NiR mRNAs was induced by nitrate and repressed by nitrate- or ammonium-derived metabolites. In addition, the expression of the root NiR gene was detectable in leaves of a tobacco nitrate reductase (NR)-deficient mutant. Thus, the regulation of expression of tobacco NiR genes is comparable to the regulation of expression of barley NR genes. PMID- 8437566 TI - Operator derepressed mutations in the proline utilisation gene cluster of Aspergillus nidulans. AB - The proline utilisation gene cluster of Aspergillus nidulans can be repressed efficiently only when both repressing nitrogen and repressing carbon sources are present. We show that two cis-acting mutations in this cluster permit the efficient transcription of the prnB gene under repressing conditions, resulting in direct or indirect derepression of two other transcripts of the pathway. These mutations are transitions that define a 5'GAGACCCC3' sequence. Similar sequences are found upstream of other genes subject to carbon catabolite repression. We propose that this sequence defines the binding site for the negatively-acting CreA protein, which mediates carbon catabolite repression in this fungus. PMID- 8437567 TI - Gene SNQ2 of Saccharomyces cerevisiae, which confers resistance to 4 nitroquinoline-N-oxide and other chemicals, encodes a 169 kDa protein homologous to ATP-dependent permeases. AB - The yeast gene SNQ2 confers hyper-resistance to the mutagens 4-nitroquinoline-N oxide (4-NQO) and Triaziquone, as well as to the chemicals sulphomethuron methyl and phenanthroline when present in multiple copies in transformants of Saccharomyces cerevisiae. Subcloning and sequencing of a 5.5 kb yeast DNA fragment revealed that SNQ2 has an open reading frame of 4.5 kb. The putative encoded polypeptide of 1501 amino acids has a predicted molecular weight of 169 kDa and has several hydrophobic regions. Northern analysis showed a transcript of 5.5 kb. Haploid cells with a disrupted SNQ2 reading frame are viable. The SNQ2 encoded protein has domains believed to be involved in ATP binding and is likely to be membrane associated. It most probably serves as an ATP-dependent permease. PMID- 8437568 TI - Molecular mechanism of the regulation of expression of plasmid-encoded mouse bacteremia (mba) genes in Salmonella serovar Choleraesuis. AB - The regulation of mouse bacteremia genes (mba genes) encoded by a 6.4 kb region on the 50 kb virulence plasmid (pKDSC50) of Salmonella serovar Choleraesuis was analyzed. The genes mba1, mba2, mba3, and mba4, are arranged in this order, and form a cluster located in the 6.4 kb mba region. We prepared four antibodies, each specific for an individual Mba protein, using synthetic peptides as antigens. Their amino acid sequences were deduced from the DNA sequence of the corresponding mba genes. Each Mba peptide antiserum was able to recognize the corresponding Mba protein produced by Escherichia coli carrying a recombinant plasmid containing individual mba genes. When the recombinant plasmid contained all four mba genes (pMKD601), three Mba proteins (Mba2, Mba3, and Mba4) were identified by Western blotting analysis using Mba antisera. These proteins could not be detected when the recombinant plasmid lacked mba1 (pMKD201). Three species of mRNA for mba2, mba3, and mba4 with different chain length were detected from pMKD601 by Northern blot hybridization, and two start sites were identified by primer extension assay. Gel mobility shift assays demonstrated that Mba1 specifically bound to a fragment containing the start sites of mRNAs. The amino acid sequence of Mba1 had significant homology to the LysR family of DNA binding proteins, possessing a characteristic helix-turn-helix DNA binding motif. The present study provides clear evidence to show that the Mba1 protein binds to the promoter region of mba2, and positively regulates the expression of mba2, mba3, and mba4 genes. PMID- 8437569 TI - Genetic analysis of the bchC and bchA genes of Rhodobacter sphaeroides. AB - This study has identified by sequence analysis a single gene in the bchC locus of Rhodobacter sphaeroides and three genes, designated bchX, Y and Z, in the bchA locus, which was previously thought to contain only a single gene. All four genes may reside within the same operon and are transcribed in the order bchC-X-Y-Z. Complementation analysis of eight transposon insertion mutants within these genes suggests that bchX, Y and Z are essential for the reduction of 2-devinyl-2 hydroxyethyl chlorophyllide a and that bchC encodes the 2-desacetyl-2 hydroxyethyl bacteriochlorophyllide a dehydrogenase. Similarity between the putative BchX protein and dinitrogenase reductase proteins suggests that BchX may also be a reductase, supplying electrons for reduction of 2-devinyl-2 hydroxyethyl chlorophyllide a. PMID- 8437570 TI - Further characterization of the respiratory deficient dum-1 mutation of Chlamydomonas reinhardtii and its use as a recipient for mitochondrial transformation. AB - The respiratory deficient dum-1 mutant of Chlamydomonas reinhardtii fails to grow in the dark because of a terminal 1.5 kb deletion in the linear 15.8 kb mitochondrial genome, which affects the apocytochrome b (CYB) gene. In contrast to the wild type where only mitochondrial genomes of monomer length are observed, the dum-1 genomes are present as a mixture of monomer and dimer length molecules. The mutant dimers appear to result from head-to-head fusions of two deleted molecules. Furthermore, mitochondrial genomes of dum-1 were also found to be unstable, with the extent of the deletion varying among single cell clones from the original mutant population. The dum-1 mutant also segregates, at a frequency of ca. 4% per generation, lethal minute colonies in which the original deletion now extends at least into the adjacent gene encoding subunit four of NAD dehydrogenase (ND4). We have used the dum-1 mutant as a recipient to demonstrate stable mitochondrial transformation in C. reinhardtii employing the biolistic method. After 4 to 8 weeks dark incubation, a total of 22 respiratory competent colonies were isolated from plates of dum-1 cells bombarded with C. reinhardtii mitochondrial DNA (frequency 7.3 x 10(-7)) and a single colony was isolated from plates bombarded with C. smithii mitochondrial DNA (frequency 0.8 x 10(-7)). No colonies were seen on control plates (frequency < 0.96 x 10(-9)). All transformants grew normally in the dark on acetate media; 22 transformants were homoplasmic for the wild-type mitochondrial genome typical of the C. reinhardtii donor. The single transformant obtained from the C. smithii donor had a recombinant mitochondrial genome containing the donor CYB gene and the diagnostic HpaI and XbaI restriction sites in the gene encoding subunit I of cytochrome oxidase (COI) from the C. reinhardtii recipient. The characteristic deletion fragments of the dum-1 recipient were not detected in any of the transformants. PMID- 8437571 TI - SecA is plastid-encoded in a red alga: implications for the evolution of plastid genomes and the thylakoid protein import apparatus. AB - Partial sequence analysis of the plastid DNA (ptDNA) from a red alga, Antithamnion sp., revealed the presence of a homologue to the Escherichia coli secA gene as well as two open reading frames (ORF 510, ORF 179). In addition a sec Y homologue has been detected on the plastid genome by heterologous hybridization. None of these genes has been found in completely sequenced chlorophytic plastid genomes. SecA and secY gene copies were also detected in the ptDNA of a chromophytic alga, indicating that secA Y may be ubiquitous in rhodophytes and chromophytes. The significance of these findings for the evolution of plastid genomes and the thylakoid protein import mechanism is discussed. PMID- 8437572 TI - A chloroplast DNA deletion located in RNA polymerase gene rpoC2 in CMS lines of sorghum. AB - Fertile lines of sorghum (Sorghum bicolor) were shown to differ from cytoplasmic male sterile (CMS) lines by the presence of a 3.8 kb HindIII chloroplast DNA fragment in the former and a smaller (3.7 kb) fragment in the latter. DNA/DNA hybridization studies showed that these two fragments are homologous. Fertile plants from S. versicolor, S. almum, S. halepense, and Sorghastrum nutans (Yellow Indiangrass) also have the 3.8 kb fragment, and CMS lines studied containing A1, A2 and A3 cytoplasms have the 3.7 kb fragment. The size difference between the two fragments was localized to a 1.0 kb SacI-HindIII fragment by restriction mapping. A 165 bp deletion, which is flanked by a 51 bp tandem repeat, was identified in the CMS lines by sequencing the clones. Comparison of the two sequences with those from maize, rice, tobacco, spinach, pea, and liverwort revealed that the deleted sequence is located in the middle of the RNA polymerase beta" subunit encoded by the gene rpoC2. The amino acid sequence deleted in the CMS lines is in a monocot-specific region which contains two protein motifs that are characteristic of several transcriptional activation factors, namely, a leucine zipper motif and an acidic domain capable of forming an amphipathic alpha helix. Further studies designed to determine whether or not the deletion is involved in CMS of sorghum are underway. PMID- 8437573 TI - Nucleotide sequence and regulated expression of the Salmonella fljA gene encoding a repressor of the phase 1 flagellin gene. AB - The nucleotide sequence of Salmonella abortus-equi fljA, which together with the phase 2 flagellin gene constitutes the fljBA operon and encodes the repressor for the phase 1 flagellin gene fliC, was determined. The repressor was predicted to be a basic protein consisting of 179 amino acid residues (M(r) = 20419 Da) encoded by ORFII. This was confirmed by the fact that host fliC is repressed by plasmid-encoded ORFII, which indeed expresses a 20 kDa product as determined by urea SDS-polyacrylamide gel electrophoresis. An amino acid sequence capable of forming a helix-turn-helix type of structure was predicted in the C-terminal region of FljA. A rho-independent intercistronic terminator was detected between fljB and fljA. Chloramphenicol acetyltransferase (CAT) assays of fusions indicated that the terminator is capable of reducing expression of fljA to the level of a few percent, relative to fljB in broth cultures and to 1% in M9 glycerol cultures. PMID- 8437575 TI - A gene, SMP2, involved in plasmid maintenance and respiration in Saccharomyces cerevisiae encodes a highly charged protein. AB - The smp2 mutant of Saccharomyces cerevisiae shows increased stability of the heterologous plasmid pSR1 and YRp plasmids. A DNA fragment bearing the SMP2 gene was cloned by its ability to complement the slow growth of the smp2 smp3 double mutant (smp3 is another mutation conferring increased stability of plasmid pSR1). The nucleotide sequence of SMP2 indicated that it encodes a highly charged 95 kDa protein. Disruption of the genomic SMP2 gene resulted in a respiration-deficient phenotype, although the cells retained mitochondrial DNA, and showed increased stability of pSR1 like the original smp2 mutant. The fact that the smp2 mutant is not always respiration deficient and shows increased pSR1 stability even in a rho0 strain lacking mitochondrial DNA suggested that the function of the Smp2 protein in plasmid maintenance is independent of respiration. The SMP2 locus was mapped at a site 71 cM from lys7 and 21 cM from ilv2/SMR1 on the right arm of chromosome XIII. PMID- 8437574 TI - nir1, a conditional-lethal mutation in barley causing a defect in nitrite reduction. AB - Eleven green individuals were isolated when 95000 M2 plants of barley (Hordeum vulgare L.), mutagenised with azide in the M1, were screened for nitrite accumulation in their leaves after nitrate treatment in the light. The selected plants were maintained in aerated liquid culture solution containing glutamine as sole nitrogen source. Not all plants survived to flowering and some others that did were not fertile. One of the selected plants, STA3999, from the cultivar Tweed could be crossed to the wild-type cultivar and analysis of the F2 progeny showed that leaf nitrite accumulation was due to a recessive mutation in a single nuclear gene, which has been designated Nir1. The homozygous nir1 mutant could be maintained to flowering in liquid culture with either glutamine or ammonium as sole nitrogen source, but died within 14 days after transfer to compost. The nitrite reductase cross-reacting material seen in nitrate-treated wild-type plants could not be detected in either the leaf or the root of the homozygous nir1 mutant. Nitrite reductase activity, measured with dithionite-reduced methyl viologen as electron donor, of the nitrate-treated homozygous nir1 mutant was much reduced but NADH-nitrate reductase activity was elevated compared to wild type plants. We conclude that the Nir1 locus determines the formation of nitrite reductase apoprotein in both the leaf and root of barley and speculate that it represents either the nitrite reductase apoprotein gene locus or, less likely, a regulatory locus whose product is required for the synthesis of nitrite reductase, but not nitrate reductase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437576 TI - Cloning and expression analysis of beta-isopropylmalate dehydrogenase from potato. AB - A full-length cDNA clone for beta-isopropylmalate dehydrogenase from potato has been isolated and sequenced. The open reading frame is 1071 bp in length encoding a protein of 357 amino acids which includes a 29 amino acid, putative chloroplastic transit peptide. The amino acid sequence shows 33.3% and 28.6% identity to beta-isopropylmalate dehydrogenases from rape and Bacillus subtilis, respectively. Southern analysis shows that the gene is present in low copy number in potato, and in single copy in tomato and Arabidopsis. The gene is expressed in all tissues of the potato plant and its expression is increased by leucine, and leucine plus threonine, in contrast to the situation in yeast and prokaryotes. The gene is also induced by sucrose in a manner similar to that seen with genes involved in carbohydrate metabolism, which indicates that there may be some interaction at the transcriptional level between genes involved in carbon and nitrogen metabolism. PMID- 8437577 TI - Characterization of the expression of a desiccation-responsive rd29 gene of Arabidopsis thaliana and analysis of its promoter in transgenic plants. AB - We characterized the expression of genes that correspond to a cDNA clone, RD29, which is induced by desiccation, cold and high-salt conditions in Arabidopsis thaliana. Northern analysis of desiccation-induced expression revealed a two-step induction process. Early induction occurs within 20 min and secondary induction occurs 3 h after the start of desiccation. Exogenous abscisic acid (ABA) induces RD29 mRNA within 3 h. Two genes corresponding to RD29, rd29A and rd29B, are located in tandem in an 8 kb region of the Arabidopsis genome and encode hydrophilic proteins. Desiccation induces rd29A mRNA with two-step kinetics, while rd29B is induced only 3 h after the start of desiccation. The expression of both genes is stimulated about 3 h after application of ABA. It appears that rd29A has at least two cis-acting elements, one involved in the ABA-associated response to desiccation and the other induced by changes in osmotic potential. The beta-glucuronidase (GUS) reporter gene driven by the rd29A promoter was induced at significant levels by desiccation, cold, high-salt conditions and ABA in both transgenic Arabidopsis and tobacco. Histochemical analysis of GUS activity revealed that the rd29A promoter functions in almost all the organs and tissues of vegetative plants during water deficiency. PMID- 8437578 TI - Identification of the entire set of transferred chloroplast DNA sequences in the mitochondrial genome of rice. AB - The entire set of transferred chloroplast DNA sequences in the mitochondrial genome of rice (Oryza sativa cv. Nipponbare) was identified using clone banks that cover the chloroplast and mitochondrial genomes. The mitochondrial fragments that were homologous to chloroplast DNA were mapped and sequenced. The nucleotide sequences around the termini of integrated chloroplast sequences in the rice mtDNA revealed no common sequences or structures that might enhance the transfer of DNA. Sixteen chloroplast sequences, ranging from 32 bases to 6.8 kb in length, were found to be dispersed throughout the rice mitochondrial genome. The total length of these sequences is equal to approximately 6% (22 kb) of the rice mitochondrial genome and to 19% of the chloroplast genome. The transfer of segments of chloroplast DNA seems to have occurred at different times, both before and after the divergence of rice and maize. The mitochondrial genome appears to have been rearranged after the transfer of chloroplast sequences as a result of recombination at these sequences. The rice mitochondrial DNA contains nine intact tRNA genes and three tRNA pseudogenes derived from the chloroplast genome. PMID- 8437579 TI - Effects of protein kinase inhibitors on in vitro protein phosphorylation and cellular differentiation of Streptomyces griseus. AB - In vitro phosphorylation reactions using extracts of Streptomyces griseus cells and gamma-[32P]ATP revealed the presence of multiple phosphorylated proteins. Most of the phosphorylations were distinctly inhibited by staurosporine and K 252a which are known to be eukaryotic protein kinase inhibitors. The in vitro experiments also showed that phosphorylation was greatly enhanced by manganese and inhibition of phosphorylation by staurosporine and K-252a was partially circumvented by 10 mM manganese. A calcium-activated protein kinase(s) was little affected by these inhibitors. Herbimycin and radicicol, known to be tyrosine kinase inhibitors, completely inhibited the phosphorylation of one protein. Consistent with their in vitro effects the protein kinase inhibitors inhibited aerial mycelium formation and pigment production by S. griseus. All these data suggest that S. griseus possesses several protein kinases of eukaryotic type which are essential for morphogenesis and secondary metabolism. In vitro phosphorylation of some proteins in a staurosporine-producing Streptomyces sp. was also inhibited by staurosporine, K-252a and herbimycin, which suggests the presence of a mechanism for self-protection in this microorganism. PMID- 8437580 TI - The consensus sequence of Kluyveromyces lactis centromeres shows homology to functional centromeric DNA from Saccharomyces cerevisiae. AB - The nucleotide sequences of five of the six centromeres of the yeast Kluyveromyces lactis were determined. Mutual comparison of these sequences led to the following consensus: a short highly conserved box (5'-ATCACGTGA-3') flanked by an AT-rich (+/- 90%) stretch of +/- 160 bp followed by another conserved box (5'-TNNTTTATGTTTCCGAAAATTAATAT-3'). These three elements were named KlCDEI, KlCDEII, and KlCDEIII respectively, by analogy with the situation in Saccharomyces cerevisiae. In addition, a second 100 bp AT-rich (+/- 90%) element, named KlCDE0, was found +/- 150 bp upstream of KlCDEI. The sequences of both KlCDEI and KlCDEIII are highly conserved between K. lactis and S. cerevisiae; however, centromeres of K. lactis do not function in S. cerevisiae and vice versa. The most obvious differences between the centromeres of the two yeast species are the length of the AT-rich CDEII, which is 161-164 bp in K. lactis versus 78-86 bp in S. cerevisiae and the presence in K. lactis of KlCDE0, which is not found in S. cerevisiae. PMID- 8437581 TI - Differential expression of two genes encoding isoforms of the ATPase involved in sodium efflux in Saccharomyces cerevisiae. AB - The ENA2 gene encoding a P-type ATPase involved in Na+ and Li+ effluxes in Saccharomyces cerevisiae has been isolated. The putative protein encoded by ENA2 differs only in thirteen amino acids from the protein encoded by ENA1/PMR2. However, ENA2 has a very low level of expression and for this reason did not confer significant Li+ tolerance on a Li+ sensitive strain. ENA1 and ENA2 are the first two units of a tandem array of four highly homologous genes with probably homologous functions. PMID- 8437582 TI - Physical linkage of the SLG and SRK genes at the self-incompatibility locus of Brassica oleracea. AB - In Brassica oleracea, the pollen-stigma interaction of self-incompatibility is controlled by a single genetically defined locus designated S. Molecular studies have identified two genes that are tightly linked to the classically defined S locus: The S-Locus Glycoprotein (SLG) gene and the S-Receptor Kinase (SRK) gene. In previous RFLP linkage analyses with probes specific for SLG and SRK, we were unable to identify any recombination events between SLG, SRK, and self incompatibility phenotype. In this paper, we use pulsed-field gel electrophoresis (PFGE) in conjunction with DNA blot analysis to characterize the S-locus region from two highly divergent self-incompatibility genotypes, S2 and S6. We establish the physical linkage of SLG and SRK in each genotype, and demonstrate that the two genes are separated by a maximum distance of 220 kb in the S6 genotype and 350 kb in the S2 genotype. Furthermore, a comparison of the data from the two genotypes reveals that a high level of polymorphism exists across the entire S locus region. PMID- 8437583 TI - A variety of epistatic interactions can occur between partially homologous transgene loci brought together by sexual crossing. AB - Epistatic interactions between unlinked transgene loci in tobacco plants were studied following sexual crosses between different transgenic lines. Three potential "modifier" transgene loci, which were structurally similar but integrated at different chromosomal locations, were tested for their ability to influence the expression of a partially homologous "target" transgene locus. After introduction of an individual modifier locus, the target locus could be either unaffected, completely inactivated and methylated or differentially sensitive, showing more complete inactivation and methylation when homozygous than when hemizygous. The implications of these results for inbreeding depression in plants are discussed. PMID- 8437584 TI - Characterization of the S7 ribosomal protein gene in wheat mitochondria. AB - By screening a wheat mitoplast cDNA bank, we have identified an open reading frame of 444 bp that has a derived amino acid sequence homologous to bacterial type S7 ribosomal proteins. This gene, designated rps7, is located upstream of one of two 26S rRNA gene copies in the wheat mitochondrial genome and is expressed as an abundant mRNA of approximately 0.7 kb. Its 5' terminus maps to the end of an 80 bp element that is closely related to sequences preceding the wheat coxII, orf25 and atp6 genes. Southern hybridization analysis indicates that rps7-homologous sequences are present in the mitochondria of rice and pea, but not soybean. PMID- 8437585 TI - Characterization of the cleavage site and the recognition sequence of the I-CreI DNA endonuclease encoded by the chloroplast ribosomal intron of Chlamydomonas reinhardtii. AB - The chloroplast ribosomal intron of Chlamydomonas reinhardtii encodes a sequence specific DNA endonuclease (I-CreI), which is most probably involved in the mobility of this intron. Here we show that I-CreI generates a 4 bp staggered cleavage just downstream of the intron insertion site. The I-CreI recognition sequence is 19-24 bp in size and is located asymmetrically around the intron insertion site. Screening of natural variants of the I-CreI recognition sequence indicates that the I-CreI endonuclease tolerates single and even multiple base changes within its recognition sequence. PMID- 8437587 TI - Fertile asymmetric somatic hybrids between Lycopersicon esculentum Mill. and Lycopersicon peruvianum var. dentatum Dun. AB - Thirteen nuclear asymmetric hybrids were regenerated under selective conditions following fusion of chlorophyll-deficient protoplasts from cultivated tomato (Lycopersicon esculentum Mill.) and gamma-irradiated protoplasts from the wild species Lycopersicon peruvianum var. dentatum Dun. All hybrid plants were classified as being asymmetric based on morphological traits, chromosome numbers and isozyme patterns. The majority of the hybrids inherited Lycopersicon peruvianum var. dentatum chloroplasts. Mitochondrial DNA analysis revealed mixed mitochondrial populations deriving from both parents in some of the hybrids and rearranged mitochondrial DNA in others. The asymmetric hybrids express some morphological traits that are not found in either of the parental species. Fertile F1 plants were obtained after self-pollination of the asymmetric hybrids in four cases. The results obtained confirm the potential of asymmetric hybridization as a new source of genetic variation, and as a method for transferring of a part of genetic material from donor to recipient, and demonstrate that it is possible to produce fertile somatic hybrids by this technique. PMID- 8437586 TI - Mutational analysis of the fission yeast p34cdc2 protein kinase gene. AB - The p34cdc2 protein serine-threonine kinase plays an essential role in the life cycle of fission yeast, being required for both the G1-S and G2-M transitions during mitotic growth, and also for the second meiotic nuclear division. Functional homologues of p34cdc2 (each ca. 60% identical to the fission yeast prototype) have been isolated from organisms as diverse as humans, insects and plants, and there is now considerable evidence supporting the view that fundamental aspects of the cell cycle controls uncovered in fission yeast will prove to be conserved in all eukaryotes. By comparing the amino acid sequences of fission yeast p34cdc2 with its higher eukaryotic counterparts it is possible to identify conserved residues that are likely to be centrally important for p34cdc2 function. Here the effects are described of mutating a number of these conserved residues. Twenty-three new mutant alleles have been constructed and tested. We show that replacing cysteine 67 with tryptophan renders the resulting mutant protein p80cdc25-independent (while neither leucine, isoleucine nor valine has this effect) and that several of the amino acids within the highly conserved PSTAIRE region are not absolutely required for p34cdc2 function. Five acidic amino acids have also been mutated within p34cdc2, which are invariant across the eukaryotic protein kinase family. Acid-to-base mutations at three of these residues resulted in a dominant-negative, cell cycle arrest phenotype while similar mutations at the other two simply abolished p34cdc2 protein function. The results are discussed with reference to the predicted tertiary structure of the p34cdc2 enzyme. PMID- 8437588 TI - SOS-independent mutagenesis in lacZ induced by methylene blue plus visible light. AB - In vitro photosensitization by visible light in the presence of methylene blue (MB-light) produces lesions in M13mp18 lacZ phage DNA, the lethal and mutagenic potential of which was analyzed after transfection into various bacterial hosts. Mutagenesis was determined with a forward mutation assay using the lacZ gene of M13mp18 as a target. When, MB-light-treated double-stranded (ds) M13mp18 DNA was used to transfect wild-type cells which were not induced for SOS functions, a fivefold increase in mutation frequency was observed at 10% survival compared to that observed with untreated DNA. Mutation frequency obtained with MB-light treated ds M13mp18 DNA was greater when transfected into the uvr A fpg-1 double mutant than that seen in uvr A, fpg-1, or umuC single mutants or in the wild type. Sequence analysis shows that in the wild-type strain, MB-light treatment of ds M13mp18 DNA results mostly in single base substitutions. The most frequent base change is the GC-->TA transversion. MB-light treatment of single-stranded (ss) M13mp18 DNA also results in an increased mutation frequency after transfection into the wild-type strain, yielding mostly G-->T transversions. Our results show that MB-light-induced mutagenesis is at least partially independent of the induction of SOS functions in Escherichia coli. The mutation spectra suggest that 8-oxo-7,8-dihydroguanine is the major promutagenic lesion in DNA. PMID- 8437589 TI - Drosophila melanogaster does not share the telomeric repeat sequence of another invertebrate, Ascaris lumbricoides. AB - The DNA at the chromosomal termini of all eukaryotes from which it has been isolated contains a characteristic sequence motif consisting of tandem arrays of a regular or irregular repeat unit. These terminal repeats are thought to be essential for the maintenance of the chromosome ends. The sequences of the terminal repeats of all vertebrates studied thus far are identical and are similar enough to those of higher plants and some protozoans to cross-hybridize. However, previous studies have not detected cross-hybridization between the DNA of Drosophila melanogaster and the terminal DNA sequences of any of several organisms tested. Recently, the first terminal DNA clone from a multicellular invertebrate, that of Ascaris lumbricoides, was reported also to consist of a tandem reiteration of a short sequence similar to those previously identified for other eukaryotes. Here I show that a probe for this sequence from A. lumbricoides fails to hybridize detectably to the DNA of D. melanogaster. Thus, in contrast to their conservation among vertebrates, the terminal chromosomal sequences appear not to be shared by all metazoan invertebrates. PMID- 8437590 TI - A pair of putative protein kinase genes (YPK1 and YPK2) is required for cell growth in Saccharomyces cerevisiae. AB - Probes derived from cDNAs encoding isozymes of rat protein kinase C (PKC) were used to screen the genome of the budding yeast Saccharomyces cerevisiae. We reported previously the isolation of the yeast PKC1 gene, a homolog of the alpha, beta, and gamma subspecies of mammalian PKC. Here we report the isolation and genetic characterization of a pair of previously described genes (YPK1 and YPK2) which are predicted to encode protein kinases that share 90% amino acid identity with each other and 44-46% identity with various isozymes of PKC throughout their putative catalytic domains. Deletion of YPK2 resulted in no apparent phenotypic defect, but loss of YPK1 resulted in slow growth. Cells deleted for both YPK1 and YPK2 were defective in vegetative growth, indicating that the protein kinases predicted to be encoded by these genes are functionally overlapping and play an essential role in the proliferation of yeast cells. The YPK1 gene was mapped to the left arm of chromosome XI and YPK2 was mapped to the right arm of chromosome XIII. PMID- 8437591 TI - Size variation of rDNA clusters in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe. AB - The higher-order organization of rRNA genes was investigated in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe. We used pulsed-field gel electrophoresis (PFGE) in combination with frequent cutter endonucleases having no recognition sites within rDNA repeating units to characterize tandem arrays of ribosomal genes in these two species. Large variations in rDNA cluster length were detected in various S. cerevisiae and S. pombe strains commonly used as PFGE molecular weight markers. This wide range of variability implies that the sizes currently assessed for chromosomes bearing rRNA genes in these organisms are unreliable since they may vary within strains by several hundreds of kilobase pairs, depending on the size of the tandem arrays of rRNA genes. Consequently, there is now a lack of reliable PFGE size standards between 1.6 Mb and 4.5 Mb, even when established yeast strains with calibrated chromosomes are used. PMID- 8437592 TI - Characterization and expression in Streptomyces lividans of cefD and cefE genes from Nocardia lactamdurans: the organization of the cephamycin gene cluster differs from that in Streptomyces clavuligerus. AB - The cefD and cefE genes of Nocardia lactamdurans, which encode isopenicillin N epimerase and deacetoxycephalosporin C synthase respectively, have been located 0.63 kb upstream from the lysine-6-amino-transferase (lat) gene. cefD contains an open reading frame (ORF) of 1197 nucleotides (nt) encoding a protein of 398 amino acids with a M(r) of 43,622. The deduced amino acid sequence exhibits 62.2% identity to the cefD gene product of Streptomyces clavuligerus. The sequence SXHKXL in isopenicillin N epimerase resembles the consensus sequence for pyridoxal phosphate binding found in several amino acid decarboxylases from Enterobacteria. cefE contains an ORF of 945 nt encoding a protein of 314 amino acids with a M(r) of 34,532, which is similar to the deacetoxycephalosporin C synthase of S. clavuligerus. Expression of both genes, cefD and cefE, in S. lividans transformants, results in deacetoxycephalosporin C synthase and isopenicillin N epimerase activities that are 10-12 times higher than those in N. lactamdurans. The cefD and cefE genes of N. lactamdurans are closely linked but the overall organization of the cephamycin gene cluster differs in N. lactamdurans and S. clavuligerus. PMID- 8437593 TI - The ORF encoding a putative ferredoxin-like protein downstream of the vnfH gene in Azotobacter vinelandii is involved in the vanadium-dependent alternative pathway of nitrogen fixation. AB - An open reading frame (ORF) in the same operon as, but downstream of, vnfH in Azotobacter vinelandii can code for a ferredoxin-like protein. The role this ORF may play in the vnf (vanadium-dependent alternative) pathway of nitrogen fixation was investigated. Site-directed mutagenesis was used to alter one base in each of the codons specifying amino acids 18 and 19 generating a unique Bg/II site. A kanamycin resistance cartridge was cloned into the Bg/II site. This construct was mobilized into A. vinelandii CA12 (delta nifHDK) strain by conjugation and the mutation was introduced into the genome by marker exchange. The resulting mutant was unable to fix nitrogen under conditions in which the vnf pathway of nitrogen fixation operates. This suggests that this ORF is functional and is essential for the vanadium-dependent alternative pathway of nitrogen fixation in A. vinelandii. PMID- 8437594 TI - Chimerism after liver transplantation for type IV glycogen storage disease and type 1 Gaucher's disease. AB - BACKGROUND: Liver transplantation for type IV glycogen storage disease (branching enzyme deficiency) results in the resorption of extrahepatic deposits of amylopectin, but the mechanism of resorption is not known. METHODS: We studied two patients with type IV glycogen storage disease 37 and 91 months after liver transplantation and a third patient with lysosomal glucocerebrosidase deficiency (type 1 Gaucher's disease), in whom tissue glucocerebroside deposition had decreased 26 months after liver replacement, to determine whether the migration of cells from the allograft (microchimerism) could explain the improved metabolism of enzyme-deficient tissues in the recipient. Samples of blood and biopsy specimens of the skin, lymph nodes, heart, bone marrow, or intestine were examined immunocytochemically with the use of donor-specific monoclonal anti-HLA antibodies and the polymerase chain reaction, with preliminary amplification specific to donor alleles of the gene for the beta chain of HLA-DR molecules, followed by hybridization with allele-specific oligonucleotide probes. RESULTS: Histopathological examination revealed that the cardiac deposits of amylopectin in the patients with glycogen storage disease and the lymph-node deposits of glucocerebroside in the patient with Gaucher's disease were dramatically reduced after transplantation. Immunocytochemical analysis showed cells containing the HLA phenotypes of the donor in the heart and skin of the patients with glycogen storage disease and in the lymph nodes, but not the skin, of the patient with Gaucher's disease. Polymerase-chain-reaction analysis demonstrated donor HLA-DR DNA in the heart of both patients with glycogen storage disease, in the skin of one of them, and in the skin, intestine, blood, and bone marrow of the patient with Gaucher's disease. CONCLUSIONS: Systemic microchimerism occurs after liver allotransplantation and can ameliorate pancellular enzyme deficiencies. PMID- 8437595 TI - Cardioversion from atrial fibrillation without prolonged anticoagulation with use of transesophageal echocardiography to exclude the presence of atrial thrombi. AB - BACKGROUND: Because atrial thrombi are poorly detected by conventional noninvasive techniques such as transthoracic echocardiography, patients with prolonged atrial fibrillation usually receive several weeks of oral anticoagulation therapy before cardioversion is attempted. We wondered whether transesophageal echocardiography, an accurate method of detecting atrial thrombi, would allow early cardioversion to be performed safely if no thrombi were identified. METHODS: A total of 669 consecutive patients admitted with the diagnosis of atrial fibrillation were screened. Patients were excluded if they were receiving long-term anticoagulation, if the duration of atrial fibrillation was two days or less, if they were not candidates for cardioversion, or if transesophageal echocardiography was contraindicated. Of 119 qualifying patients, 94 agreed to participate; the average duration of atrial fibrillation was 4.5 weeks. Participating patients underwent transthoracic echocardiography and transesophageal echocardiography followed by cardioversion if no thrombi were seen. Short-term anticoagulation with heparin was used in 80 patients before cardioversion, and 60 patients received warfarin for one month after cardioversion. RESULTS: Fourteen atrial thrombi were identified in 12 patients (13 percent), and 12 of the 14 thrombi were visualized only on transesophageal echocardiography. Cardioversion was deferred in all 12 patients. Two of these 12 patients died suddenly; 4 of the 10 surviving patients underwent uneventful cardioversion after prolonged oral anticoagulation. Seventy-eight of the 82 patients without thrombi underwent successful cardioversion to sinus rhythm (47 by means of antiarrhythmic drugs and 31 by electrical cardioversion), all without long-term oral anticoagulation. None of these patients (95 percent confidence interval, 0 to 4.6 percent) had an embolic event. CONCLUSIONS: In patients with atrial fibrillation of unknown or prolonged duration who are not receiving long term anticoagulation, atrial thrombi are detected by transesophageal echocardiography in only a small minority (13 percent in our study). Our preliminary data suggest that if transesophageal echocardiography excludes the presence of thrombi, early cardioversion can be performed safely without the need for prolonged oral anticoagulation before the procedure. PMID- 8437596 TI - The effects of treatment with interleukin-1 alpha on platelet recovery after high dose carboplatin. AB - BACKGROUND: Thrombocytopenia is a frequent side effect of cancer chemotherapy and commonly limits attempts to escalate drug doses. To determine whether interleukin 1 alpha could ameliorate carboplatin-induced thrombocytopenia, we combined it with high-dose carboplatin in 43 patients with advanced neoplasms. METHODS: High dose carboplatin (800 mg per square meter of body-surface area) was administered alone to a control group. Subsequent patients were randomly assigned to receive the same dose of carboplatin with interleukin-1 alpha, administered either before or after carboplatin. Interleukin-1 alpha was given intravenously at a dose of 0.03, 0.1, or 0.3 microgram per kilogram of body weight per day for five days. RESULTS: Carboplatin alone consistently produced thrombocytopenia with a median nadir of 19,000 platelets per cubic millimeter and a median of 10 days with less than 100,000 platelets per cubic millimeter. All 15 patients receiving interleukin-1 alpha before carboplatin had similar findings. In contrast, 5 of the 15 patients given one of the two higher doses of interleukin-1 alpha after carboplatin had minimal thrombocytopenia (nadir, 91,000 to 332,000 platelets per cubic millimeter). In the 10 patients given 0.3 microgram of interleukin-1 alpha per kilogram after carboplatin treatment, the platelet count recovered to 100,000 per cubic millimeter significantly earlier than in either the control group (P = 0.002) or the patients who received interleukin-1 alpha before carboplatin (P = 0.003), with the median times to recovery in the three groups being 16, 21, and 23 days, respectively. At the highest dose of interleukin-1 alpha, toxicity was substantial (but reversible), requiring inpatient support for hypotension, supraventricular arrhythmias, and pulmonary-capillary leak. CONCLUSIONS: Interleukin-1 alpha can accelerate the recovery of platelets after high-dose carboplatin therapy and may be clinically useful in preventing or treating thrombocytopenia induced by chemotherapy. PMID- 8437597 TI - Brief report: graft-versus-host disease associated with transfusion of blood from unrelated HLA-homozygous donors. PMID- 8437599 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 11-1993. A 52-year-old man with cardiomyopathy and pulmonary disease. PMID- 8437598 TI - Hospital expenditures in the United States and Canada. AB - BACKGROUND: Expenditures per capita for hospitals are higher in the United States than in Canada. If the United States had the same spending pattern as Canada, the annual savings in 1985 would have exceeded $30 billion. METHODS: We used data from published sources, computer files, and institutional reports to compare 1987 costs for acute care hospitals on three levels: national (the United States vs. Canada), regional (California vs. Ontario), and institutional (two California hospitals vs. two Ontario hospitals). Expenditures per admission were adjusted for the case mix of patients, prices of labor and other resources, and outpatients visits. RESULTS: The United States had proportionately fewer hospital beds than Canada (3.9 vs. 5.4 per 1000 population), fewer admissions (129 vs. 142 per 1000 population), and shorter mean stays (7.2 vs. 11.2 days). Higher costs per admission in the United States were explained in part by a case mix that was more complex by 14 percent and by prices for labor, supplies, and other hospital resources that were higher by 4 percent. Hospitals in the United States provided relatively less outpatient care, particularly in emergency departments (320 vs. 677 visits per 1000 population). After all adjustments, the estimate of resources used for inpatient care per admission was 24 percent higher in the United States than in Canada and 46 percent higher in California than in Ontario. The estimated differences between the two pairs of California and Ontario hospitals were 20 and 15 percent. CONCLUSIONS: Canadian acute care hospitals have more admissions, more outpatient visits, and more inpatient days per capita than hospitals in the United States, but they spend appreciably less. The reasons include higher administrative costs in the United States and more use of centralized equipment and personnel in Canada. PMID- 8437600 TI - Mixed chimerism and immunologic tolerance. PMID- 8437601 TI - Should transesophageal echocardiography be used to guide cardioversion? PMID- 8437602 TI - Northern exposure--can the United States learn from Canada? PMID- 8437603 TI - Tacrine in Alzheimer's disease. PMID- 8437604 TI - Tacrine in Alzheimer's disease. PMID- 8437605 TI - Tacrine in Alzheimer's disease. PMID- 8437606 TI - Tacrine in Alzheimer's disease. PMID- 8437607 TI - Evaluation of a breast mass. PMID- 8437608 TI - Evaluation of a breast mass. PMID- 8437609 TI - Evaluation of a breast mass. PMID- 8437610 TI - Viral culture of HIV in neonates. PMID- 8437611 TI - Viral culture of HIV in neonates. PMID- 8437612 TI - Anaphylactic reaction to gonadotropin-releasing hormone. PMID- 8437613 TI - Cell wall fractions from Paracoccidioides brasiliensis induce hypergammaglobulinemia. AB - The antibody response against the antigen sheep red blood cells (SRBC) was investigated in mice pre-treated with formalin-killed Paracoccidioides brasiliensis or with cell wall fractions of the fungus. Pre-treatment with P. brasiliensis, as well as with the Fl fraction and beta-glucan significantly increased the anti-SRBC antibody response in the experimental groups as compared to the control group that received only SRBC. This immunomodulatory effect varied with the different doses employed and with pre-treatment time. We conclude that the cell wall fractions of P. brasiliensis might play an important role in the hypergammaglobulinemia associated with Paracoccidioidomycosis. PMID- 8437614 TI - The influence of post-filtration washing on the in vitro assay of Candida albicans adherence to human buccal epithelial cells. AB - A simple in vitro assay technique was used to determine the effect of post filtration washing on the adherence of C. albicans (NCPF 3736) to human buccal epithelial cells (BEC). Washing was carried out with a range of volumes of phosphate buffered saline (PBS), viz. 0, 5, 10 and 20 ml, at a standard flow rate. Both the number of C. albicans adherent to BEC and the percentage of BEC with adherent C. albicans were significantly decreased (p < 0.001 for each of these measures) after washing with 5 ml PBS. Further increases in the volume of PBS did not significantly decrease either measure of adherence. These data indicate that only a small volume of PBS, 5 ml, is required to achieve the removal of non-adherent C. albicans from the surface of BEC. The result of the adherence assay is not significantly affected by increasing the volume of PBS used. It is concluded that considerable savings in time may be made through using only a small (5 ml) volume of washing buffer at a standard flow rate. PMID- 8437615 TI - In vitro vomitoxin exposure alters IgA and IgM secretion by CH12LX B cells. Relationship to proliferation and macromolecular synthesis. AB - The CH12LX cell line was used as a clonal model to assess the direct effects of vomitoxin on IgM and IgA secretion in B cells. When vomitoxin was included in LPS driven CH12LX B cell cultures, it had multiple effects on Ig secretion. Whereas vomitoxin doses of 115 and 120 ng/ml caused 50% inhibition (ID50) of IgA and IgM production, respectively, toxin concentrations in the 5 to 50 ng/ml range slightly stimulated IgA production. However, low vomitoxin doses did not induce switching of membrane IgM+ CH12LX B cells to membrane IgA+. Total cell number was unaffected at vomitoxin concentrations up to 100 ng/ml but dropped markedly at 200 ng/ml (ID50 = 170 ng/ml). Using the MTT reduction assay as another measure of viability and cell function, vomitoxin was also inhibitory (ID50 = 130 ng/ml). Both thymidine incorporation and leucine incorporation were also inhibited by the toxin with estimated ID50s being 120 and 110 ng/ml, respectively. The results indicate that although at high doses, vomitoxin inhibits proliferation, Ig secretion and DNA/protein synthesis in the clonal B cell model, the toxin marginally stimulated IgA secretion at lower doses. PMID- 8437616 TI - Britain urged to lift barriers to investment in biotechnology. PMID- 8437617 TI - Europeans protest against patent for Harvard mouse. PMID- 8437618 TI - Institute files for patents on first Japanese sequences. PMID- 8437619 TI - Drugged by tobacco. PMID- 8437620 TI - Telephone book of life. PMID- 8437621 TI - The powers and pitfalls of parsimony. AB - Parsimony analysis is a powerful tool for the study of biological evolution. It is used to construct phylogenetic trees, to evaluate alternative hypotheses objectively, and to study evolutionary pattern and process. Yet, as comparative data sets expand, the pitfalls of parsimony analysis are catching experts and novices alike. PMID- 8437622 TI - Landmark stability is a prerequisite for spatial but not discrimination learning. AB - Neurons sensitive to both place and direction from distinct regions of the hippocampal formation, allometric relationships between spatial learning and hippocampal structure and pronounced impairments in spatial learning after lesions in this area, indicate that the hippocampal formation subserves allocentric spatial learning. To learn more about the process of spatial representation, we have developed a task that provides independent control of both landmark and directional cues. On the basis of physiological and behavioural work, this task also makes it possible to investigate the relevance of associative learning principles, such as predictability, to the spatial domain. We report here that although rats learn to discriminate between landmarks on the basis of their proximity to a reliably predicted food reward, they will only learn to use them to represent its location if they maintain stable locations within a geometric frame of reference. PMID- 8437623 TI - Qa-2 molecules are peptide receptors of higher stringency than ordinary class I molecules. AB - Class I molecules of the major histocompatibility complex (MHC) transport peptides to the cell surface for surveillance by T cells. Ligand specificity is stringent and differs from allele to allele. Here we report analysis of natural ligands of 'unconventional' glycophosphatidyl-anchored mouse class I molecules, Qa-2. The function of these molecules is unclear; they can serve as recognition structures for 'unrestricted' cytotoxic T cells but have not been found to present peptides to T cells, although the DNA sequence suggests a similar peptide binding groove to that of 'conventional' class I molecules, and other unconventional class I molecules can present antigens in a few cases. Pool sequencing of natural Qa-2 ligands shows that Qa-2 molecules are indeed peptide receptors, having ligand specificity similar to that of conventional class I molecules, that is, a predominant length of nine amino acids, anchor positions, and hydrophobic termination of peptides. But ligand specificity is much more stringent than with other class I molecules: of the nine positions, two are anchors and four have rather limited occupancy. PMID- 8437624 TI - Drug assay using antibody mimics made by molecular imprinting. AB - Ligand-binding assays are used for determination of minute amounts of substances in the bloodstream. Such assays require a receptor that specifically binds the substance of interest. The receptor used is often an antibody, but antibodies require special handling and a costly production procedure. We have used molecular imprinting, a method for creating selective recognition sites in synthetic polymers, to prepare polymers that mimic antibody combining sites. Molecular imprints made against theophylline and diazepam showed strong binding and cross-reactivity profiles similar to those of antibodies. Here we describe a new radiolabelled ligand-binding assay, the molecularly imprinted sorbent assay, which uses antibody mimics. This assay accurately measures drug levels in human serum, with results comparable to those obtained using a well established immunoassay technique. Antibody mimics, which are stable and readily prepared by molecular imprinting, may provide a useful general alternative to antibodies. PMID- 8437625 TI - Efficient adenovirus-mediated transfer of a human minidystrophin gene to skeletal muscle of mdx mice. AB - Duchenne progressive muscular dystrophy is a lethal and common X-linked genetic disease caused by the absence of dystrophin, a 427K protein encoded by a 14 kilobase transcript. Two approaches have been proposed to correct the dystrophin deficiency in muscle. The first, myoblast transfer therapy, uses cells from normal donors, whereas the second involves direct intramuscular injection of recombinant plasmids expressing dystrophin. Adenovirus is an efficient vector for in vivo expression of various foreign genes. It has recently been demonstrated that a recombinant adenovirus expressing the lac-Z reporter gene can infect stably many mouse tissues, particularly muscle and heart. We have tested the ability of a recombinant adenovirus, containing a 6.3 kilobase pair Becker-like dystrophin complementary DNA driven by the Rous sarcoma virus promoter to direct the expression of a 'minidystrophin' in infected 293 cells and C2 myoblasts, and in the mdx mouse, after intramuscular injection. We report here that in vivo, we have obtained a sarcolemmal immunostaining in up to 50% of fibres of the injected muscle. PMID- 8437626 TI - Transcriptional differences in polymorphic and conserved domains of a complete cloned P. falciparum chromosome. AB - Classical genetic studies on the human malaria parasite Plasmodium falciparum have been hampered by a complex life cycle which alternates between vertebrate and invertebrate hosts. Consequently, only a few genetic crosses have been performed so far. In addition, molecular genetics has provided only limited access to the genes of this pathogen, a consequence of an unusually high A + T content. To overcome these limitations we have constructed an ordered telomere-to telomere contig map of P. falciparum chromosome 2 by isolating overlapping yeast artificial chromosome clones. This approach was used to examine the strain dependent polymorphisms commonly observed for P. falciparum chromosomes. Our analysis reveals that polymorphisms of chromosome 2 are restricted to regions at either end, representing 20% of the chromosome. Transcription mapping of the entire chromosome suggests a compartmentalization of chromosome 2 into a transcribed central domain and silent polymorphic ends. PMID- 8437627 TI - Evidence for an essential non-Watson-Crick interaction between the first and last nucleotides of a nuclear pre-mRNA intron. AB - Nuclear pre-messenger RNA splicing requires the action of five small nuclear (sn) RNAs, U1, U2, U4, U5 and U6, and more than 50 proteins. The mechanistic similarity of nuclear pre-mRNA splicing and group II self-splicing suggests that many of the central processes of nuclear pre-mRNA splicing are based on RNA-RNA interaction. To understand the mechanism of pre-mRNA splicing, the interactions, and their temporal relationships, that occur between the snRNAs and the pre-mRNA during splicing must be identified. Several snRNA-snRNA and snRNA-intron interactions have been demonstrated but the putative RNA-based interactions that recognize the AG dinucleotide at the 3' splice site during 3' cleavage and exon ligation are unknown. We report here the reciprocal suppression between 5' and 3' splice site mutations in the yeast actin intron, and propose that the 3' splice site is positioned for 3' cleavage and exon ligation, at least in part, through a non-Watson-Crick interaction between the guanosines at the 5' and 3' splice sites. PMID- 8437628 TI - [Headache: the 13th in the dozen of emergency stage 3]. PMID- 8437629 TI - [Oral rehydration therapy in Europe]. PMID- 8437630 TI - [Introduction of immunotherapeutic agents in clinical practice; current status concerning anti-endotoxin antibody HA-1A in the control of sepsis]. PMID- 8437631 TI - [Oral rehydration solution based on nutrition: a promising method]. PMID- 8437632 TI - [Magnetic resonance angiography]. PMID- 8437633 TI - [Immunotherapy using the anti-endotoxin antibody HA-1A in patients with sepsis syndrome; good results in relation to treatment with placebo]. AB - Passive immunization with a human anti-endotoxin monoclonal IgM antibody (Centoxin, HA-1A) was recently studied in patients with suspected Gram-negative sepsis. Comparison of the results obtained in the Amsterdam subpopulation with those in a larger international study population of which the Amsterdam patient group was a part, showed that it had been possible to select a patient population in which HA-1A has an 'intention-to-treat' effect based upon clinical criteria (a decrease in mortality compared with placebo by 42% (p = 0.04) and in the larger study by 9% (p = 0.24). Until a clinically useful test becomes available, identification of patients who have a high likelihood of Gram-negative sepsis and who would benefit from anti-endotoxin immunotherapy with HA-1A should be based upon the history and evaluation of underlying disease, infection status, severity and progression of the disease. The severely ill patients thus selected should receive treatment as early as possible. PMID- 8437634 TI - [Immunotherapy using the anti-endotoxin antibody HA-1A (Centoxin) in patients with sepsis syndrome; fair results following protocol selection of patients]. AB - OBJECTIVE: Evaluation of HA-1A treatment in patients with the sepsis syndrome. DESIGN: Descriptive. SETTING: Department of intensive care, Academic Medical Centre, Amsterdam. PATIENTS AND METHODS: Intensive-care patients with the sepsis syndrome and shock or organ failure with a presumptive diagnosis of Gram-negative infection were eligible for treatment with HA-1A. We analysed and compared the results with those of the double-blind, randomized HA-1A study by Ziegler et al. RESULTS: Between May 1991 and March 1992, 27 patients were treated with HA-1A. The mortality rate was 59% (16/27). Among the 11 patients with a Gram-negative bacteraemia mortality was 7/11, much higher than in the Ziegler study (30%). In comparison with the HA-1A study we selected sicker patients: the mean APACHE II score was higher, 93% of our patients were in shock and 85% had organ failure. More patients presented with an intra-abdominal sepsis and mortality in this group was very high (11/14). In patients with a Gram-negative bacteraemia the delay between the onset of the sepsis syndrome and the administration of HA-1A was longer (median 22 h versus 14.3 h in the Ziegler study, mean 30 versus 20 h). CONCLUSION: HA-1A does not appear to be beneficial in critically ill patients with a longstanding sepsis syndrome, especially not if an intra-abdominal sepsis is apparent. Therefore, we decided not to use H-1A until additional data become available. Additional objective inclusion criteria are needed to improve the identification of the patient group that may benefit from treatment with HA-1A. PMID- 8437635 TI - [Cost-effectiveness analysis of human monoclonal antibody HA-1A in patients with sepsis syndrome]. AB - The efficiency of prescribing HA-1A for sepsis patients is analysed by comparing direct medical costs and effects. Effects are estimated on the basis of published data from a randomised clinical trial. Costs are analysed by combining data from the same trial with expectations about hospital days. Average costs per life year gained are estimated at DF1. 25,000. Sensitivity analysis is applied and the efficiency of treating patients with HA1A is shown to depend highly on the expected duration of survival after successful treatment. This leads to the advice to take epidemiologic knowledge into special account before setting the indication for using HA-1A. PMID- 8437636 TI - [What is self-evident but does not occur as a matter-of-course; observations on the report about biological psychiatry]. PMID- 8437637 TI - [Financing of health research. The Dutch Kidney Foundation]. PMID- 8437638 TI - [Wrong questions, erroneous answers; an absurd choice]. PMID- 8437639 TI - [Wrong questions, erroneous answers; an absurd choice]. PMID- 8437640 TI - [Wrong questions, erroneous answers; an absurd choice]. PMID- 8437641 TI - [Spontaneous regression of cancer; report of 7 cases]. PMID- 8437642 TI - [The value of new diagnostic techniques in Alzheimer's disease]. PMID- 8437643 TI - [There is no such thing as the CVA]. PMID- 8437644 TI - [Thyroid hormones and depressive disorders--critical overview and perspectives. Part 1: Clinical aspects]. AB - This review gives a critical synopsis of the literature on the interaction between thyroid hormones and depressive illness, a phenomenon that has been well known for over 100 years. Possible perspectives for clinical practice and research are discussed. The most relevant conclusions and hypotheses being as follows: 1. Thyroid hormone disorders (hypo- and hyperthyroidism) may induce almost any psychiatric symptom or syndrome. However, no disease of the thyroid causes symptoms typical of a specific diagnosis. 2. Depressed patients are euthyroid, at least in terms of their laboratory values. Abnormal values are all not specific for any psychiatric diagnosis. They are probably due to intervening variables such as stress or weight loss, or simply to methodological problems. 3. Attempts to treat depressive patients with TRH or T3 have not produced any results of clinical relevance. However, some preliminary reports of a prophylactic effect of high-dose thyroxine in previously resistant "rapid cycling" patients are most promising. 4. All antidepressant and prophylactic therapies (antidepressant drugs, sleep deprivation, ECT, lithium, and carbamazepine) affect thyroid hormone concentrations. During treatment with antidepressants, carbamezepine, and lithium, these changes are significantly correlated to clinical response. PMID- 8437645 TI - [Drug treatment of anorexia nervosa and bulimia nervosa. A review]. AB - With the apparent increase in prevalence of anorexic and bulimic eating disorders, the search for effective treatments for these disorders has been intensified in recent years. In this review the results of psychopharmacological studies of patients with anorexia or bulimia nervosa are presented and analysed. The focus of this review is on controlled studies. Although a variety of psychopharmacological substances has been tested in patients with anorexia nervosa, the outcome of controlled studies has been generally disappointing. A possible differential therapy effect of cyproheptadine needs replication: in one study it enhanced body weight gain in non-bulimic anorexics, while it appeared to hinder weight gain in bulimic anorexics. The issue of prophylaxis of osteoporosis in chronic low-weight anorexics has received increasing attention in recent years, and pharmacological prophylaxis appears indicated in this patient group. The results of psychopharmacological treatment studies of patients with bulimia nervosa have overall been more favourable than those of anorexic patients. Statistically significant effects concerning the reduction of bulimic or depressive symptoms in bulimia nervosa has been demonstrated for tricyclic antidepressants (imipramine, desipramine), serotonergic agents (fluoxetine, d fenfluramine), non-selective monoamine-oxydase-inhibitors (isocarboxazide, phenelzine) and trazodone. The antibulimic effect appears not to be associated with the antidepressant effect. Theoretical, methodological and practical issues concerning pharmacological treatment of anorexic and bulimic eating disorders are presented and discussed. PMID- 8437646 TI - [Diagnosis of alcohol dependence]. AB - The dependence syndrome has gained central importance in diagnosing alcohol abuse disorders, as shown by its incorporation in ICD-10 and DSM-III-R. After dealing with historical concepts of alcoholism, the concurrent and predictive validity of the dependency syndrome is discussed in relation to aspects of typology and comorbidity, and to neurobiological variables. Diagnostic instruments are assessed and research perspectives indicated. PMID- 8437647 TI - [Berlin follow-up study of eating disorders in adolescence. I. Inpatient follow up]. AB - Following an introductory comment regarding the purpose of this longitudinal study on eating disorders in adolescence, findings based on assessment of the illness course during inpatient treatment are presented. A multidimensional research design that included both self rating and rating by others demonstrates a clear reduction of symptoms in a number of different areas. This is evident in the 'semantic differential' self-evaluation with regard to body-image and personality, the patient's attitudes toward eating, specific characteristics of the eating disorder syndrome, the self-concept, various personality attributes, physical complaints, and the sense of well-being. The analogous assessments made by therapists and ward staff members also indicated definite improvement with regard to those symptoms that are specific to eating disorders. PMID- 8437648 TI - [Psychiatric disorders in elderly general hospital patients: incidence and long term prognosis]. AB - As part of a survey conducted in six general-hospital departments of internal medicine, in the neighbouring cities of Mannheim and Ludwigshafen (total pop. 470,000), 626 patients in the age range 65 to 80 years, all admitted from private addresses, were screened by means of a standardized questionnaire (Cognitive and Affective Screening of the Elderly--'CASE'). All patients whose scores indicated possible mental abnormality, together with a proportion of those having normal scores, were then examined in greater detail, using the Clinical Psychiatric Interview. Following correction, the screening results indicated a frequency of 30.2% for clinically significant psychiatric disturbance, made up of 9.1% with organic mental disorders and 21.1% with functional mental illness only. These rates are considerably higher than could be expected on the basis of a field study of the background population. One year after hospital discharge, the numbers of deaths and of admissions to long-stay care were established for the whole sample, and in addition, individually matched sub-samples of 100 mentally ill and 100 mentally normal patients were reinvestigated. A second follow-up of the matched sub-samples was undertaken after a further interval of 5.6 years on average. The results of follow-up show that 75% of the identified cases ran a chronic or recurring course, while only a small proportion proved to be transient reactions to physical illness or hospital admission. In general, the psychiatrically ill patients had a relatively unfavourable outcome, even after the effects of age, physical disability and other relevant variables had been controlled for. When compared with the matched group of mentally normal patients, they manifested a 43% excess of mortality, and an increase of 157% in the risk for having to be admitted to long-stay care. PMID- 8437649 TI - [Young chronic patients: how can we better manage the most difficult cases among them? A review of the literature]. AB - The term "Young Adult Chronic Patients" (YACPs) was first used in the early eighties in the American literature. It describes a new generation of young mentally ill persons who become chronic, no longer in the clinic but in the community. They are characterized less by a common psychopathology than by their social deficits and their behaviour, which frustrates caregivers and makes them feel helpless. Possible causes of the YACP phenomenon and shortcomings of the care provided for them are discussed. The authors consider that a flexible, individually tailored and comprehensive multi-program system of services including case-management is needed to treat the YACPs better in future. Finally, advantages and problems of the YACP concept are discussed. PMID- 8437650 TI - [Monoamine oxidase inhibitors in the treatment of obsessive disorders. Two case reports and review of the literature]. AB - Two patients who were admitted to hospital with severe obsessive compulsive disorders (OCD) improved dramatically after treatment with the MAO-Inhibitor tranylcypromine. The possibility of treating obsessive-compulsive disorders with MAO-Inhibitors and serotonergic drugs is discussed. PMID- 8437651 TI - The significance of spinal cord compression as the initial manifestation of lymphoma. AB - Eighteen patients with spinal cord compression caused by previously undiagnosed lymphoma were treated at our institution between 1976 and 1991. There were 14 male and 4 female patients (mean age, 58.2 years). The absence of bony involvement on radiographic images was a feature in 16 of the cases. All patients underwent laminectomy for decompression and tissue diagnosis, after which 5 underwent radiotherapy, 3 underwent chemotherapy, and 10 underwent combined modality treatment. The functional outcome was improvement in 8 patients and no change in 10; no patient worsened after surgery. Eleven had advanced disease at diagnosis, while seven had limited disease, including three patients with localized extradural lymphoma. There were 16 cases of non-Hodgkin's lymphoma and 2 of Hodgkin's disease. Two patients had T-cell lymphoma and were among the longest survivors. DNA flow cytometry identified the low-grade tumors as diploid with very low proliferative indices, while the high-grade tumors all had high indices. At a mean observation time of 41.7 months, five patients have died of their disease, and seven remain in complete remission. Survival is markedly better than that reported for other malignant extradural tumors; however, even limited stage lymphoma can behave aggressively. Similarities in age, sex distribution, histological features, and the results of flow cytometry suggest behavior similar to extranodal lymphoma at other sites. Surgery to provide a tissue diagnosis, followed by combined radiotherapy and chemotherapy, is indicated for all cases. PMID- 8437652 TI - Aneurysm of the posterior cerebral artery: report of eleven cases--surgical approaches and procedures. AB - Eleven cases of an aneurysm of the posterior cerebral artery are reported. All 11 aneurysms were saccular, and 3 were either giant or large. The aneurysms arose from the P1 segment in three patients, the P1-P2 junction in three patients, the P2 segment in three patients, and from the P3 segment in two patients. In all, 10 patients underwent surgery. All P1 and P1-P2 junction aneurysms were treated with the pterional approach. Three P2 and two P3 aneurysms were managed by the subtemporal approach. Two small aneurysms in the series were treated by coating the aneurysmal dome, two by clipping the afferent artery, and all other saccular type aneurysms were treated by clipping the aneurysmal neck. Seven patients had either an excellent or good outcome; two had poor results; and one patient died. The operative approaches and procedures are also discussed in relation to the anatomy of posterior cerebral artery aneurysms. PMID- 8437653 TI - Supratentorial ependymomas of the first two decades of life. Long-term follow-up of 20 cases (including two subependymomas). AB - In order to better elucidate the lesser known aspects of the biological behavior and prognosis of supratentorial ependymomas in children and young adults, we studied a series of 20 patients, ages 1 to 20 years. The tumor site was extraventricular in 14 cases and intraventricular in 6 (including one third ventricle tumor). Histologically, according to World Health Organization criteria, there were 12 ependymomas (E), 2 subependymomas (SE), and 6 malignant ependymomas (ME). Of the 18 patients surviving surgery, 12 (66.6%) are alive and disease free 63 to 252 months (mean, 146 mo) after the operation; 9 harbored an E, 2 had an SE and 1 had an ME. Four patients are now out of risk of recurrence according to Collin's law. Six of the long-term survivors (50%), four E and two SE, did not receive postoperative radiotherapy. However, two patients with E, initially treated by surgery alone, had a recurrence and one subsequently died. Two ME patients showed signs of spinal metastases after subsequent operation for recurrence and shortly before death. Considering the partially good results as well as failures after surgery alone in our and in other series and the risks of irradiating the child's brain, we tried to elucidate in what cases radiotherapy could be reasonably withheld, or alternatively, when prophylactic craniospinal irradiation should be prescribed. The main conclusions of our study are the following: 1) Radical surgery alone is a reasonable option as the initial treatment for lateral ventricle tumors and for solid extraventricular tumors located far from eloquent brain areas, provided the histology is benign, especially if of the SE type.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437654 TI - The expectant treatment of "asymptomatic" supratentorial epidural hematomas. AB - Seventy-four patients with a traumatic epidural hematoma (EDH) and a Glasgow Coma Scale score of more than 12 received expectant treatment; 14 subsequently underwent surgical evacuation of the EDH. A patient with initial brain computed tomograms (CT) showing an EDH volume of more than 30 ml, a thickness of more than 15 mm, and a midline shift beyond 5 mm tended to require surgery within 3 days of the injury when the brain had exhausted its compensatory mechanism and yielded to the expanding EDH. After the 3-day period, in the absence of neurological symptoms, the presence of the EDH may not be an indication for surgical evacuation or hospitalization beyond 7 days. In our patients, the presence of a skull fracture in the temporal bone, the heterogeneous density of the EDH in the CT scan, or the 6-hour period between the CT study and the injury did not significantly increase the failure rate of nonsurgical treatment. Although a zero mortality was achieved in this series, these guidelines may not be applicable to the management of an infratentorial EDH. PMID- 8437655 TI - The role of cortex in central pain syndromes: preliminary results of a long-term technetium-99 hexamethylpropyleneamineoxime single photon emission computed tomography study. AB - The role of the somatosensory cortex in central pain syndromes is widely questioned. Two recent position emission tomography studies detected a strong activation of the parietal and cingular cortices after brief nociceptive stimuli. On the other hand, a recent single photon emission computed tomography study found no cortical activation in five patients affected by central poststroke pain and algodystrophia. In this study, we present the single photon emission computed tomography findings in five patients suffering from central pain syndromes. Two of these, one with facial postrhizotomy anesthesia dolorosa and the other with central poststroke pain, showed a decrease of blood flow in the parietal lobe, further decreasing after stimulation by nonpainful maneuvers. Our results suggest that somatosensory cortical areas might be involved in the generation of anomalous pain states in some cases of central pain syndromes. PMID- 8437656 TI - Use of vascularized fat from the rectus abdominis myocutaneous free flap territory to seal the dura of basicranial tumor resections. AB - Resection of large skull base tumors may sometimes result in extirpation defects that are not amenable to local tissue closure. Patients with these tumors require free tissue transfer for closure of the intracranial space after basicranial tumor extirpation. The deep inferior epigastric artery supplies the rectus abdominis muscle and the skin and subcutaneous tissue of the lower abdomen. The closure of massive, central defects can be performed with a free flap designed from the ample rectus abdominis vascular territory. This free tissue donor site has abundant and reliable well-vascularized skin and subcutaneous tissue that can be customized to seal these tenuous areas and provide three-dimensional reconstruction. We have modified the rectus abdominis myocutaneous free flap in seven patients for reconstruction of the skull base. The subcutaneous fat was sculptured to form a soft, vascularized "cork" and was used for obliteration of the irregular deep portions of defects at the midcranial base against the repaired or unrepaired dura. All patients who had the vascularized fat used to obliterate the deep space had successful closure of the defect without cerebral spinal fluid leak. There were two wound infections and one donor-site hernia in this group. The judicious use of the vascular territory of the deep inferior epigastric vessels can accomplish secure three-dimensional reconstruction of the skull base. The flap can be reliably transferred, and the vascularized subcutaneous fat can be used to sequester and seal the dura repair.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437657 TI - Occipitocervical fusion with a five-millimeter malleable rod and segmental fixation. AB - Although occipitocervical fusion is frequently used for instability of the upper cervical spine and the occipitocervical articulation, most currently used techniques have one or more of the following disadvantages: the necessity for sublaminar wires, the use of occipital screws, a fixed angle of instrumentation, or the necessity for routine postoperative halo immobilization. Moreover, many reported techniques are associated with a high rate of nonunion or instrumentation failure. We present our experience with a technically simple method of obtaining rigid occipitocervical arthrodesis using a 5-mm malleable rod that is fixed to the skull by a pair of wires passed through four suboccipital burr holes. Segmental spinal fixation is achieved with Wisconsin interspinous wires and is occasionally supplemented with sublaminar wires. Supplemental autogenous bone graft is used in all cases. A cervical collar is routinely used for postoperative immobilization. The results of treatment were retrospectively reviewed in 16 patients with an average age of 49.4 years (range, 9-69). Mean follow-up was 24 months (range, 12-36 mo). The indication for fusion was instability of the occiput-C1-C2 complex as a result of Chiari malformation, rheumatoid disease, skull base tumor resection, basilar invagination, ankylosing spondylitis, Down's syndrome, cervical laminectomy, and trauma. The average number of levels fused was 5.4 (range, O-C3 to O-T3). Successful occipitocervical arthrodesis was achieved in all but one of the surviving patients. The single patient with a pseudarthrosis was successfully managed with supplemental bone grafting and halo immobilization. There were two deaths from medical complications in chronically ill patients. Other complications included one postoperative instrumentation loosening, one myocardial infarction, and one superficial occipital decubitus. In conclusion, rodding and segmental interspinous wiring is an effective, technically simple method of obtaining rigid occipitocervical fixation, which obviates the need for bulky orthoses. PMID- 8437658 TI - Extracranial application of the frameless stereotactic operating microscope: experience with lumbar spine. AB - The frameless stereotactic operating microscope has expanded the potential application of modern stereotaxis to procedures outside of the intracranial compartment by removing the constraint of a rigid frame. We studied seven patients all of whom had a history, examination, and imaging studies consistent with lumbosacral spinal pathology for which they subsequently underwent surgery with the operating microscope. The ability of the frameless stereotactic system with preoperative computed tomography data to locate the level of the lesion as well as define the boundary of the spinal pathology intraoperatively was assessed. In parallel with this application of the frameless system, we analyzed the relationship between the lumbar intervertebral disc spaces (L3-L4, L4-L5, L5 S1) and skin surface fiducials using lateral radiographs. In seven patients with extracranial cases (six herniated lumbar discs and one lumbar spondylolysis with Grade I spondylolisthesis) who underwent operations by this system, the accuracy of the digitization component of the system with respect to localization of an independent test fiducial was 3.28 mm (SD, 0.61). The accuracy of the entire system in locating the independent fiducial within the viewing plane was 6.05 mm (SD, 4.04). Disc space localization had a far greater error of 28.81 mm (SD, 7.49). There was no consistent pattern to the magnitude or direction of the displacement of the lumbar intervertebral discs with respect to the fiducial markers in the sagittal plane. Although accuracy at the level of the fiducial plane was similar to that of intracranial applications, paraspinal tissue and vertebral column deformations rendered poorer accuracy with deeper structures. PMID- 8437659 TI - A preliminary report on the use of laser-Doppler flowmetry during tethered spinal cord release. AB - Neurological deterioration in the tethered cord syndrome has been postulated to result from a compromise of blood flow in the distal spinal cord. In order to evaluate vascular perfusion in human subjects, a new technique of laser-Doppler flowmetry was used to monitor continuously the microcirculation of the distal spinal cord during surgery for tethered cord release in 10 children. For further comparison, five children undergoing selective dorsal rhizotomy were also monitored. In the tethered cord syndrome group, spinal cord blood flow before untethering was a mean of 12.6 ml/min per 100 g of tissue and increased in all cases after release to a mean of 29.4 ml/min per 100 g of tissue. All patients improved neurologically. The selective dorsal rhizotomy group had a preoperative mean spinal cord blood flow of 30.8 ml/min per 100 g of tissue, which was not altered by the operative procedure. Significant improvement occurs in distal spinal cord blood flow after tethered cord release, which may be representative of an important mechanism in the pathophysiology of the tethered cord syndrome. PMID- 8437661 TI - Intraoperative recordings of evoked extraocular muscle activities to monitor ocular motor nerve function. AB - During 22 operations in 18 patients, we stimulated the ocular motor nerves electrically, intracranially, and recorded compound muscle action potentials (CMAP) directly from the extraocular muscles with a ring electrode that we developed. Recording electrodes were applied in 52 instances to the superior rectus, medial rectus, superior oblique, or lateral rectus muscle and to the levator palpebrae superioris in 2 instances; CMAP were recorded successfully from 22 muscles. Evoked CMAP were not recorded in 2 instances because of problems with recording equipment; in the remaining 30 instances, no evoked CMAP were recorded because 1) the oculomotor or abducens nerve was not exposed during the operation; or 2) the recording electrode on the superior oblique muscle had not been properly placed to record trochlear nerve CMAP. Placement of this electrode is difficult. Ocular motor nerve function was analyzed preoperatively and postoperatively to evaluate the usefulness of this intraoperative electrophysiological monitoring method in preventing damage to ocular motor nerves. The results of this study showed that monitoring enables surgeons to locate precisely ocular motor nerves that would otherwise have been overlooked and thus possibly injured during surgery. Monitoring results also confirmed the surgeons' visual findings, thus helping the surgeons operate with greater confidence. Further, intraoperative monitoring provided us with some insights into the pathophysiology of ocular motor nerve dysfunction caused by skull base lesions; we documented electrophysiologically the occurrence of the slowing of conduction in the ocular motor nerves. We conclude that monitoring ocular motor nerve CMAP can reduce the incidence of surgical complications such as functional blindness due to inadvertent sectioning of one of these nerves and that it would be worthwhile to conduct studies of this technique in many more cases to validate our findings. PMID- 8437660 TI - Modification of cortical stimulation for motor evoked potentials under general anesthesia: technical description. AB - This pilot study presents a possible modification of direct cortical electrical stimulation technique for the recording of motor evoked potentials under general anesthesia. The exposed primary motor cortex was stimulated by a short train of anodal rectangular pulses at high frequency (300-500 Hz), while the compound muscle action potentials were recorded from the forearm and hand muscles. When compared with the traditional way of eliciting movement of the extremities by applying a train of pulses at lower frequency (50-60 Hz), muscle responses were obtainable at an intensity of much lower charge. It is suggested that this stimulation achieves a repetitive activation of the corticomotoneuronal tract. Responses could be continuously recorded throughout surgery and seemed to respond to surgical manipulation affecting the motor pathways. This technique seems to be applicable for intraoperative monitoring of motor pathways but requires further optimization of stimulation and recording parameters before wider clinical applications are possible. PMID- 8437662 TI - Total intravenous anesthesia with propofol for burst suppression in cerebral aneurysm surgery: preliminary report of 42 patients. AB - Forty-two patients underwent cerebral aneurysm clipping at our institution in 1991, 35 with a ruptured aneurysm and 7 with an unruptured aneurysm. Preoperatively, 22 patients with a ruptured aneurysm were graded I or II according to the World Federation of Neurosurgical Societies and 21 underwent an operation on the first day. All underwent a standard cerebral protective general anesthesia, combining propofol with fentanyl, arterial normotension (mild hypertension with volume loading and/or dopamine during temporary clipping and once the aneurysm was secured), normocarbia or slight hypocarbia, brain relaxation with lumbar drainage, mannitol and propofol, and electroencephalogram burst suppression when temporary clipping (> or = 2 min) was required. Propofol doses for induction were 1.8 +/- 0.1 mg/kg (mean +/- standard error); for maintenance, doses were 86 +/- 3.5 micrograms/kg per min; and for burst suppression doses were 500 micrograms/kg per min. After clipping, the propofol dose rate was reduced to allow early recovery and neurological examination in the operating room. In 21 patients, temporary clipping was required for a mean duration of 8.8 +/- 1.3 minutes (range, 2-29); none of these patients deteriorated as compared with their preoperative neurological state. Twenty-four of the 42 patients (57%) had a Glasgow Coma Outcome Scale (GOS) score of 1, 7 patients had a GOS score of 2, 8 had a score of 3, and 3 had a score of 5. Thirty two patients were extubated in the operating room with a mean GOS Score of 13.2 +/- 0.5, and 10 were extubated later in the intensive care unit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437663 TI - Stereotactic radiosurgery: principles and comparison of treatment methods. AB - Methods of stereotactic radiosurgery are reviewed and compared with respect to technical factors and published clinical results. Heavy-ion beams, the Leksell cobalt-60 gamma knife, and the conventional linear accelerator (linac) are compared with respect to dosimetry, radiobiology, treatment planning, cost, staffing requirements, and ease of use. Clinical results on the efficacy of treatment of arteriovenous malformations are tabulated, and other applications of radiosurgery are described. It is concluded that although there are dosimetric and radiobiological advantages to charged-particle beams that may ultimately prove critical in the application of radiosurgery to large (> 30 mm) lesions, these advantages have not yet demonstrated clinical effect. On the other hand, equally excellent clinical results are obtained for small lesions with photon beams--the gamma knife and the linac. There are only minor differences between gamma and x-ray beam dose distributions for small, spherical-shaped targets. Mechanical precision is superior for the gamma knife as compared with the linac. The superior mechanical precision is of limited importance for most clinical targets, because inaccuracy of cranial target localization based on radiological imaging is greater than the typical linac imprecision of +/- 1 mm. Treatment planning for the linac is not standardized, but existing systems are based on well-known algorithms. The linac allows flexible, ready access to individualized beam control, without intrinsic field size limitations. Thus, it is more readily possible to achieve homogeneous dose distributions for nonspherical targets with one or more dimensions greater than 25 mm, as compared with that achieved with the gamma unit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437664 TI - Silicone rubber microangiography of acute spinal cord injury in the rat. AB - The purpose of this study was to investigate the acute changes in the large vessels and microvasculature of the spinal cord after acute clip compression injury in the rat. Nineteen female Wistar rats underwent acute compression of the spinal cord at C8-T1 at 53 g for 1 min. Silicone rubber was injected into the ascending aorta at 15 minutes, 1, 4, or 24 hours after injury. An additional nine rats served as normal controls. The perfused spinal cords were cleared by the alcohol-methylsalicylate technique. The results showed that, in the normal rat, the centrifugal arterial system from the sulcal arteries provided the major blood supply to the gray matter and the lateral and ventral white matter extending all the way to the pial surface. In the normal rat, there were large veins in the posterior columns coursing longitudinally in the parasagittal plane at the base of the posterior columns. The injured spinal cords displayed marked ischemia and hemorrhage at the injury site. The hemorrhage predominated in the gray matter and posterior white columns and extended rostrally and caudally for 2 to 7 mm in each direction from the injury site. Remote hemorrhages originated from damage to the large parasagittal veins in the posterior columns. Extravasations of silicone rubber were frequently seen at the earlier posttraumatic times and often originated from the sulcal arteries or their branches at the injury site. Occluded sulcal arteries were identified at the injury site at 4 and 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437665 TI - Nerve growth factor receptor expression in medulloblastomas and the potential role of nerve growth factor as a differentiating agent in medulloblastoma cell lines. AB - Nerve growth factor (NGF) has the potential to induce cellular differentiation in various neoplastic and nonneoplastic cell lines. In this study, our aim was to determine NGF receptor (NGFr) status in medulloblastoma specimens and cell lines and to investigate whether NGF could act as a potential differentiating agent for this common pediatric brain tumor. Paraffin-embedded tumor tissue from 10 patients with the diagnosis of medulloblastoma was retrospectively analyzed to determine the frequency of NGFr expression. Of the 10 tumor specimens evaluated, 4 were positive for NGFr; however, NGFr staining was confined to only 5 to 8% of the cells in a randomly scattered pattern. No colocalization was present with neuronal, glial, or vascular structures. In addition, two medulloblastoma cell lines established in our laboratory were also evaluated for NGFr. In this study, we also examined the effects of retinoic acid, 12-O-tetradecanoyl-phorbol-13 acetate, and NGF on medulloblastoma cell lines to evaluate their effect on morphological differentiation and NGFr expression. Although these agents failed to cause NGFr expression in our cell lines, morphological alteration was noticed in only one of the cell lines with retinoic acid. Therefore, because of the lack of de novo or induced NGFr expression, it is unlikely that NGF will be useful as a potential therapeutic differentiating agent for medulloblastomas. PMID- 8437666 TI - Effect of U88999E on experimental cerebral vasospasm in rabbits. AB - U88999E, 7-[4,(4, 4'-difluorobenzhydryl)piperazino-1-methyl]-4- isopropyl-2 methoxy-2,4,6-cycloheptatrien-1-one hydrochloride, is a recently developed tropolone derivative that inhibits lipid peroxidation and also acts as a calcium antagonist. The effects of U88999E on basilar artery tone were examined in two model systems: 1) an in vitro preparation of arterial rings that measures isometric tension, and 2) an in vivo model of cerebral vasospasm measuring arterial diameter. U88999E elicited dose-dependent relaxation of preconstricted arterial rings maintained in vitro. Ring preparations were preconstricted using elevated potassium (40 mmol/L), uridine triphosphate (10(-3) mol/L), or endothelin-1 (10(-8) mol/L); U88999E reversed these constrictions across a concentration range of 10(-8) to 10(-5) mol/L. The potency of U88999E for relaxing preconstricted vessels was slightly less than that observed for flunarizine or diltiazem. A dose-dependent, relaxing effect of U88999E on potassium-induced contractions was observed in the presence of calcium concentrations ranging from 0.03 to 20 mmol/L. Vasospasm of basilar arteries after subarachnoid hemorrhage was inhibited in a dose-dependent and significant manner by intravenous injections of U88999E. Animals receiving intraperitoneal injections of U88999E also exhibited a tendency for reduced vasospasm; however, this effect did not achieve statistical significance. These findings suggest that U88999E may be useful in the prevention of cerebral vasospasm after subarachnoid hemorrhage. PMID- 8437668 TI - Decade of the brain: National Institute of Neurological Disorders and Stroke. PMID- 8437667 TI - Pathophysiology of brain swelling after acute experimental brain compression and decompression. AB - Global ischemia was created by controlled expansion of an epidural balloon for 25 minutes in Group A (six cats) and for 5 minutes in Group B (six cats). The alterations of intracranial pressure, arteriovenous oxygen content difference, cerebral metabolic rate of oxygen, cerebral blood flow, and electroencephalogram were observed until brain death or 24 hours' survival with normal intracranial pressure. The animals were then killed for brain histological examination. In four other cats, a 2% solution of Evans blue dye (4 mg/kg) was injected intravenously--immediately after deflation--resulting in 25 minutes of global ischemia. Two other cats received 5 minutes of global ischemia. The cats were killed 1 hour later. Abrupt swelling occurred in Group A, and no swelling was found in Group B. A transient absolute hyperemia was found immediately after deflation in both groups. The cerebral blood flow and cerebral metabolic rate of oxygen decreased markedly with low arteriovenous oxygen content difference and flat electroencephalogram in Group A, compared with gradual recovery of cerebral blood flow and cerebral metabolic rate of oxygen with high arteriovenous oxygen content difference and reappearance of electroencephalogram activity in Group B. The extravasation of Evans blue was observed on the compressed cerebral hemisphere, thalamus, hypothalamus, and brain stem in swelling animals and only on the compressed hemisphere in nonswelling animals. Histologically, the damage and congestive dilation of capillary, degeneration, and necrosis of neuronal and glial cell were found prominently on the hypothalamus and brain stem in the swelling group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437669 TI - Multiple spinal meningiomas: a case of 47 distinct lesions in the absence of neurofibromatosis or identified chromosomal abnormality. AB - The authors present a unique case of multiple spinal meningiomas with the late development of intracranial lesions. The patient had 47 distinctly separate, yet histologically identical, lesions excised, with many others noted at the time of surgery and by radiographic studies. He was evaluated for neurofibromatosis and was found to have neither Type I nor Type II. Genetic analysis, including restriction fragment length polymorphism analysis, was performed and detected no abnormalities. PMID- 8437670 TI - Vertebral hemangioma symptomatic during pregnancy--report of a case and review of the literature. AB - A spinal tumor complicating pregnancy is a rare condition. A 25-year-old woman who became paraplegic during the 35th week of her second pregnancy presented during the postpartum period. She underwent two surgical interventions, and the cord compression caused by a T5 vertebral body hemangioma with laminar involvement and extradural extension was relieved. The occurrence of vertebral hemangiomas during pregnancy is discussed; the radiological features with special reference to magnetic resonance imaging are outlined; and cases from the literature are reviewed. PMID- 8437671 TI - "Acquired" Chiari I malformation after multiple lumbar punctures: case report. AB - The authors present the history of a patient with a Chiari I malformation "acquired" after multiple traumatic lumbar punctures. The genesis of tonsillar descent is believed to be related to persistent leakage of cerebrospinal fluid secondary to the multiple traumatic lumbar punctures. The topic of acquired Chiari I malformations and complications of lumbar puncture is reviewed. PMID- 8437672 TI - Stereotactic management of benign pineal region cysts: report of two cases. AB - Recent case reports describing the open resection of symptomatic benign cysts of the pineal region have noted that the results of stereotactic management of such cysts have not been reported. We report the results of the stereotactic aspiration of benign pineal region cysts in two patients with symptomatic ventriculomegaly secondary to obstruction of the aqueduct. Stereotactic aspiration produced several cubic centimeters of brown-to-yellow fluid that was negative for tumor on cytological examination. Ventriculomegaly and symptoms were relieved without complications by the procedure in one patient who remains asymptomatic after 30 months of follow-up. In the second patient, persistent ventriculomegaly demonstrated on computed tomography resulted in the placement of a ventriculoperitoneal shunt; however, this was removed several months later during an episode of appendicitis and the patient remained asymptomatic without the shunt. The symptoms and ventriculomegaly recurred 71 months postaspiration, and the cyst was reaspirated. Ten months later, she remains asymptomatic. Options for managing such patients include open resection, shunting, and stereotactic aspiration. The relative merits of each approach are discussed. PMID- 8437673 TI - Symptomatic cysts of the pineal gland: stereotactic diagnosis and treatment of two cases and review of the literature. AB - We report two cases of pineal gland cysts, both in young girls, causing aqueductal stenosis and symptomatic hydrocephalus, which were diagnosed and treated by Talairach's stereotactic method. This procedure permitted aspiration of the cyst content, normalization of aqueductal stenosis, and a differential histological diagnosis. Postoperative computed tomographic scan examination showed a stable reduction of the cystic volume and a complete clearance of the hydrocephalus. At present, the two patients are clinically normal and are leading a productive life (follow-up, 42 and 40 mo). It is important that this kind of nonneoplastic lesion be identified, in order to avoid confusion with pineal tumors and possible inappropriate treatment. Pineal cysts rarely become symptomatic. Up to the present, only 27 symptomatic cases have been described in the literature. Of those, signs of intracystic bleeding were found in 17 of the 21 cases in which the cyst contents were known. Moreover, in our own two cases, numerous hemosiderin-laden macrophages were present in the cystic fluid. We think, therefore, that intracystic bleeding has been the determining factor for the occurrence of symptoms in most of these cases. The authors underline the advantages of this type of stereotactic management, which can provide both diagnosis and treatment and thus avoid the possible risks of surgical excision and/or of radiotherapy. PMID- 8437674 TI - Remote-control vascular occluder: technical note. AB - We have designed a new remote-control vascular occluder for the temporary control of arterial blood flow. It is a modification of the biopsy forceps used in stereotactic surgery. The arm of the occluder is flexible and can be set so that it does not disturb the surgeon's view. The occluder is positioned with the blades open on the vessel to be occluded. This device, which is held with a self retaining retractor connected to the head frame, enables an immediate on-off remote control of arterial occlusion by closing and releasing the blades with a closing button and releasing lever, respectively. Partial closure of the blades is also feasible. The device can be set in a narrow operating field, when proximal control of a parent artery is necessary at its segment distant from the exposed operating field. It can be used in a variety of vascular cases, including giant aneurysms and large arteriovenous malformations. PMID- 8437675 TI - Even small doses of morphine might provoke "luxury perfusion" in the postoperative period after craniotomy. PMID- 8437676 TI - Video endoscopic sympathectomy using a fiberoptic CO2 laser to treat palmar hyperhidrosis. PMID- 8437677 TI - Role of prostaglandins in delayed cerebral ischemia after subarachnoid hemorrhage. PMID- 8437678 TI - Memory for different aspects of complex visual scenes after unilateral temporal- or frontal-lobe resection. AB - Delayed recognition memory for different aspects of complex visual scenes was examined in 65 patients with unilateral temporal- or frontal-lobe excisions and 15 normal control subjects. Right anterior temporal lobectomy, irrespective of the extent of hippocampal removal, impaired memory for figurative detail (the visual characteristics of the objects in a scene) and spatial composition (the arrangement of the filled and unfilled space in a scene). In contrast, only patients with right temporal-lobe lesions that included extensive hippocampal removal were impaired at detecting changes in the spatial location of specific objects. A subsequent study provided no evidence that right temporal lobectomy impairs the immediate recognition of these types of visual information, suggesting that the impairments observed after a delay represent a failure of retention or retrieval rather than of encoding. PMID- 8437679 TI - Frontal lobe and frontal-striatal substrates for different forms of human cognitive flexibility. AB - Frontal lobe and basal ganglia lesions have been associated with similar cognitive impairments, although their specialized roles in behavior are likely to be different. We examined whether these structures mediate distinctive or overlapping aspects of a complex behavioral process that has been associated with both neural sites, i.e. cognitive flexibility. Patients with focal ischemic lesions to the frontal lobe and basal ganglia were compared on two forms of cognitive flexibility: (1) shifting response set (i.e. reactive flexibility), and (2) producing a diversity of ideas (i.e. spontaneous flexibility). Results indicated that frontal lobe and basal ganglia damage each caused a similar degree of impairment in reactive flexibility, both groups performing at a significantly lower level than posterior cortical lesion and normal comparison groups. However, frontal lobe damage markedly disturbed spontaneous flexibility, while performance after basal ganglia lesion was significantly higher and comparable to posterior cortical lesions. Findings suggest that the frontal lobe and basal ganglia participate differently in the neural substrate of cognitive flexibility. The frontal lobe appears to mediate spontaneous flexibility. The production of diverse ideas may require direct cortical-cortical interactions by the frontal lobe in order to access knowledge systems with novel strategies that transcend the most common semantic linkages. In contrast the corticostriate system appears to mediate reactive flexibility, as the frontal lobe, basal ganglia and their interconnections are required for its operation. PMID- 8437680 TI - Stimulus cancellation by macaques with unilateral frontal or parietal lesions. AB - Monkeys' spontaneous behaviors in cancelling a variety of visual and somatosensory stimuli were measured before, and acutely after, unilateral periarcuate (N = 16) and inferior parietal (n = 14) cortical removals. Postoperative behavior was analyzed for both severity of change from the preoperative baseline, and for the type of behavior (perceptual or premotor) affected by the lesion. Overall the two lesion groups could not be differentiated by severity or type of deficit. In two tasks, premotor deficits, manifest as extreme disuse of the hand contralateral to the lesion, were significantly worse in the parietal than the frontal group. In a third, the frontal group showed a greater perceptual deficit, manifest as marked preference for acting within ipsilesional space, than the parietal. In the three remaining tasks, premotor and perceptual deficits were equal in the two groups. These quantitative behavioral data suggest that deficits are more highly contingent upon task requirements than upon lesion sites. This in turn suggests that frontal and parietal association cortical fields each play multiple, and sometimes interchangeable, roles in the spatially directed attention and motor behavior of the monkey. PMID- 8437681 TI - Line bisection errors in visual neglect: misguided action or size distortion? AB - The rightward line bisection errors made by patients with visuospatial neglect can be explained as due to a spatially misdirected response, which would be predicted on either of two accounts. An alternative view, however, is that such patients actually misperceive the left half of a horizontal line as being shorter than the right half. We have tested this possibility directly in three neglect patients, by giving them prebisected lines: they were found to judge a central transection mark as lying nearer to the left end of the lines. We were also able to test one of the patients on a series of size comparisons using computer generated patterns. She was found to judge horizontal lines as shorter in the left half of visual space than in the right. This was also true for comparisons of the areas of nonsense figures. However she did not make such constant errors when comparing the lengths of vertical lines. It is suggested that an attentional deficit in left hemispace may result in the underestimation of horizontal extent. This would act in combination with misdirected reaching to determine the magnitude of line bisection errors. PMID- 8437682 TI - Re-orientation of attention in Parkinson's disease: an extension to the vibrotactile modality. AB - Parkinson's disease (PD), a disorder of the dopaminergic nigro-striatal pathway, is associated with both motor and cognitive impairments, including perhaps the ability to focus attention. Disturbances of attentional processes were further examined in a series of vibrotactile choice reaction time (cRT) experiments involving biased probabilities of event occurrence, or valid/invalid precueing. Results of three experiments suggest that PD subjects, compared to controls, are less adept at maintaining attention in space. The performance of the PD subjects improved, however, when they were permitted to direct their gaze to one hand or the other, and when valid external precues were provided before each trial. Observed similarities between the cognitive and motor deficits of PD subjects support the notion that there is a close coupling between the mechanisms coordinating attention and movement. PMID- 8437683 TI - A left visual field bias for semantic encoding of unattended words. AB - Previous studies have shown that verbal processing in both normal individuals and a split-brain patient can be strongly affected by the semantic category of an unattended word presented to the left visual field (LVF). The effect was interpreted in terms of inhibition, since responses were slower when the unattended LVF word belonged to the same category as the target word. The present experiment discriminated between two alternative explanations for this finding. Subjects were presented with two letter strings, one in central vision and one to the left or right of centre. Subjects made a speeded lexical decision to the central string, and were instructed to ignore the lateral string. When a word was presented to the LVF subjects responded more slowly when it was semantically related to the central word. When an unattended word was presented to the RVF, its semantic relationship to the central word had no effect on decision latency. This finding is discussed in relation to views of performance laterality and selective attention. PMID- 8437684 TI - Cognitive strategies and hypothesis testing during discrimination learning in Parkinson's disease. AB - This study investigated the nature and extent of impairments in the use of hypotheses and cognitive strategies in medicated subjects with idiopathic Parkinson's disease (PD) and matched control subjects. PD subjects did not differ from controls in solving one- or two-dimensional discrimination learning problems, but showed impairment on four-dimensional problems which did not appear to be attributable to memory deficits. They achieved fewer correct solutions, used fewer hypotheses, and were less likely to use appropriate lose-shift strategies following negative feedback. The pattern of findings was similar to those previously reported for subjects with frontal lobe lesions. PMID- 8437685 TI - A dissociation of shape discrimination and figure-ground perception in a patient with normal acuity. AB - We report the case of a 21-year-old man who sustained brain damage due to anoxia. His visual acuity was normal and his colour perception was adequate if not completely normal. However, his shape discrimination was so impaired that he had great difficulty distinguishing a square from an oblong or a large square from a smaller square. At the same time, other aspects of his shape perception were remarkably intact. His performance on a shape detection task was good. He had no difficulty on tests of figure-ground (boundary) segmentation and his perception of subjective and illusory contours appeared to be normal. S.M.K.'s performance on a number of tasks is compared with that of a patient (F.G.P.) previously reported who showed the opposite pattern of deficit (Kartsounis and Warrington, Neuropsychologia 29, 969-980, 1991). This evidence of a double dissociation between two components of shape perception is discussed in the context of a neurophysiological model of the organization of the visual system. PMID- 8437686 TI - New criteria for the diagnosis of vascular dementia: do we know enough yet? PMID- 8437687 TI - Epidemiology, education, and the ecology of Alzheimer's disease. PMID- 8437688 TI - Use of twin cohorts for research in Alzheimer's disease. AB - The causes of Alzheimer's disease (AD) remain a mystery despite the recent identification of several putative environmental risk factors and the discovery of several linked genetic loci and point mutations associated with the disease. Particularly uncertain is the generalizability of the genetic findings to the common forms of disease encountered in clinical practice or population research. Twin studies of AD can illuminate causal mechanisms, both genetic and environmental. This consensus document explores the rationale for such twin studies, as well as a number of methodologic problems that render them difficult to implement or interpret. We review existing twin studies of AD and note several ambitious new studies. Finally, we delineate several practical strategies for the near future of twin research in AD. PMID- 8437689 TI - Human walking and higher-level gait disorders, particularly in the elderly. PMID- 8437690 TI - Mitochondrial DNA alterations as a source of human disorders. AB - The mitochondrial genome has an underdeveloped "DNA repair repertoire" compared with the nuclear genome, making the mitochondrial DNA more susceptible to mutations by endogenous factors such as defects of the mitochondrial polymerase itself, and by exogenous factors such as radiation and UV light. Increased sensitivity to mutagenic factors may account for the mitochondrial DNA polymorphism within ethnic groups and the mitochondrial diseases associated with all mitochondrial DNA mutations, including DNA depletion. The presence in highly developed organisms of a DNA repair repertoire less organized in the mitochondria than in the nuclei might be a source of biologic dysfunction relevant also to aging and cell death. Uncorrected mitochondrial DNA modifications may determine lethal and severe diseases or asymptomatic biochemical dysfunctions. Considering the long life span and the complex metabolism of highly developed cells, the tendency to produce and accumulate mitochondrial DNA mutations may assume a pathogenetic role with aging. PMID- 8437691 TI - Pick's disease versus Alzheimer's disease: a comparison of clinical characteristics. AB - The clinical recognition of Pick's disease depends on its differentiation from Alzheimer's disease (AD). To identify distinguishing clinical features, we reviewed the clinical records of 21 patients with pathologically confirmed Pick's disease and matched them by sex, age of onset, and duration of dementia with 42 patients having pathologically confirmed AD. In the absence of temporal or frontal lobar atrophy on CTs, all the Pick patients and none of the AD patients had three of five clinical features: presenile onset (before age 65), an initial personality change, hyperorality, disinhibition, and roaming behavior. In addition, the Pick patients had a tendency toward reiterative and other speech disturbances. These findings suggest that Pick patients are potentially distinguishable from AD patients on the basis of clinical manifestations. PMID- 8437692 TI - Relationship between cigarette smoking and Alzheimer's disease in a population based case-control study. AB - We investigated whether cigarette smoking is negatively associated with Alzheimer's disease (AD) in a population-based, frequency-matched, case-control study of 152 AD patients and 180 controls. Ever having smoked was associated with lower risk of AD (adjusted odds ratio = 0.61; 95% confidence interval: 0.37 0.99). Additional multivariate analyses demonstrated that education and history of hypertension modified this association. The direction of the modification was for higher education level and history of hypertension to further reduce the risk. The "dose-response" pattern showed the greatest risk reduction among those who smoked least and suggests a biologic mechanism of a dose-dependent up regulation of nicotinic (cholinergic) brain receptors. These data, although consistent with current opinion about pathophysiology of AD, do not suggest smoking should be used as a preventive strategy for AD. PMID- 8437694 TI - The visual variant of Alzheimer's disease: a clinicopathologic case study. AB - A 59-year-old man developed problems with reading and driving. When first examined, he had great difficulty locating and identifying items by sight. Visual acuity was normal, but contrast sensitivity for low spatial frequencies was severely impaired. The peripheral visual fields were moderately constricted with depressed flicker fusion frequencies, more on the right. Color identification was preserved. The difficulties in identifying and locating objects by sight were aggravated by increasing the complexity and multiplicity of the items in the field of vision and by changing the ambient illumination. Intellect and memory were relatively intact, except for difficulty with calculations. Over a 12-year course the visual defects steadily worsened, and eventually memory and language skills failed. Social manners, perseverance, and affect remained normal. Postmortem examination showed cortical atrophy, predominantly posterior, with abundant neurofibrillary tangles and senile plaques. The density of the tangles was correlated with the severity of the atrophy, being highest in the occipitoparietal areas and lowest in the frontal lobes. Alzheimer's disease can preferentially affect the posterior cerebral hemispheres and cause a dementia presenting with, and dominated by, visual disturbances. PMID- 8437693 TI - Long-term and high-dose piracetam treatment of Alzheimer's disease. AB - Preclinical research suggests that piracetam (a nootropic drug) may improve cognitive functions, but previous studies have failed to demonstrate a clear benefit for the treatment of Alzheimer's disease (AD). We report a 1-year, double blind, placebo-controlled, parallel-group study with a high dose of piracetam (8 g/d per os) in 33 ambulant patients with early probable AD. Thirty subjects completed the 1-year study. No improvement occurred in either group, but our results support the hypothesis that long-term administration of high doses of piracetam might slow the progression of cognitive deterioration in patients with AD. The most significant differences concerned the recall of pictures series and recent incident and remote memory. The drug was well-tolerated. PMID- 8437696 TI - Magnetic resonance imaging in hereditary and idiopathic ataxia. AB - We used magnetic resonance imaging (MRI) to study brain and spinal cord morphology in hereditary and idiopathic ataxia. Our interest was in whether the classical neuropathologic categories--cerebellar cortical atrophy (CCA), olivopontocerebellar atrophy (OPCA), and spinal atrophy (SA)--could be identified in vivo and which clinical phenotype corresponded to which morphologic category. To this end, we measured the size of the cerebellar vermis, cerebellar hemispheres, fourth ventricle, middle cerebellar peduncles, basis pontis, medulla oblongata, and cervical spinal cord on T1-weighted images of 61 patients and 24 healthy controls. Five patients with Friedreich's ataxia (n = 7) and all with late-onset Friedreich's ataxia (n = 3) had SA without major involvement of the brainstem or cerebellum. Morphologic findings in patients with early-onset cerebellar ataxia with retained tendon reflexes (n = 11) were heterogeneous: six patients had MRI findings compatible with CCA, and two patients had a combination of SA and CCA. The three remaining patients had an atypical pattern of atrophy. Similarly, the morphologic changes in patients with autosomal-dominant cerebellar ataxia with additional noncerebellar symptoms (ADCA-I; n = 13) were nonuniform: atrophic changes typical for CCA, OPCA, or SA were each present in one case, four patients had a combination of OPCA and SA, and the remaining patients could not be assigned to one of the morphologic categories. In autosomal-dominant cerebellar ataxia with a pure cerebellar syndrome (ADCA-III; n = 6), all patients except one had CCA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437695 TI - Time course of postanoxic akinetic-rigid and dystonic syndromes. AB - Twelve previously normal patients with anoxic brain damage due to various causes are described. The mean age at anoxia was 27.4 years. Six patients, in their fourth decade or older, developed an early akinetic-rigid syndrome; the mean interval between anoxia and akinetic-rigid syndrome was 3.1 months (range, less than 1 week to 12 months). Four of these six patients also developed dystonia, usually after some months. Six other patients, all children or young adults, developed a pure dystonic syndrome; the mean interval between anoxia and dystonia was 9.7 months (range, 1 week to 36 months). Dystonia was generalized and progressed over a mean period of 21.9 months (range, 3 to 96 months). Severe bulbar involvement was common. Age determined whether an akinetic-rigid or a dystonic syndrome developed in our patients and those reported in the literature. Many, but not all, patients had lesions on brain imaging (or at autopsy). In those with visible lesions in the basal ganglia, those with dystonia tended to have damage in putamen, while those with an akinetic-rigid syndrome tended to have damage in the globus pallidus. There were exceptions. PMID- 8437697 TI - Permanent global amnesia with unknown etiology. AB - Three patients developed severe and selective memory impairment with no known cause, one during a period of a few days and two others during a period of 1 to 2 years. In two of these patients, the amnesia has been stable and circumscribed for 5 to 6 years. The third patient appears to have declined in cognitive functions during the past year, at the age of 78, after 6 years of stable, circumscribed amnesia. Neuropsychological testing reveals severe impairment in the ability to learn verbal and nonverbal material as well as retrograde amnesia covering at least 20 years. CT and routine brain MRIs were uninformative. Subsequently, a high-resolution protocol for imaging human hippocampus with MR revealed that the hippocampal formation was markedly reduced in size in all three patients. The pattern of cognitive impairment and the MR findings are similar to the findings in other patients with chronic amnesia due to a known anoxic or ischemic episode, and differ from the findings in amnesic patients with alcoholic Korsakoff's syndrome. We suggest that the amnesia may be due to ischemic damage to medial temporal lobe brain structures important for memory. PMID- 8437698 TI - Intramedullary spinal sarcoidosis: clinical and magnetic resonance imaging characteristics. AB - We present a retrospective series of the clinical and MRI findings in 16 patients with intramedullary spinal sarcoidosis (ISS), including 12 patients studied with gadolinium-DTPA. The spectrum of MRI findings includes leptomeningeal enhancement, fusiform spinal cord enlargement, focal or diffuse intramedullary disease, and spinal cord atrophy. We present a classification of ISS correlating the clinical progression and the temporal sequence of MRI abnormalities. Improvement occurred in five of 12 patients (42%) treated with immunosuppressive therapy. PMID- 8437699 TI - Coxiella (Q fever)-associated myelopathy. AB - We describe six men with a slowly progressive myelopathy characterized by asymmetric, incomplete spinal cord syndrome manifested with a thoracic sensory level, mild spastic paraparesis, and urinary incontinence. The spinal cord lesions were evident by MRI in four of them. Coxiella burnetii infection was confirmed in the blood of all patients by immunofluorescence microscopic assay (IFA) and transmission electron microscopy (TEM). In two patients, we detected C burnetii by TEM and IFA using CSF from the patients inoculated onto fresh peripheral blood lymphocyte. Four patients, treated with appropriate antibiotics, responded either with partial resolution of symptoms or arrest of further neurologic progression. In three, the MRI lesions decreased in size. PMID- 8437700 TI - Methylprednisolone selectively affects dystrophin expression in human muscle cultures. AB - Glucocorticoid therapy slows the progression of Duchenne muscular dystrophy. In muscle cultures, the addition of the glucocorticoid methylprednisolone increases myogenesis in most normal mixed and clonal cultures. Conversely, in some normal clonal and most dystrophic cultures, methylprednisolone inhibits fusion. However, in fusion-arrested normal and Becker muscular dystrophy cultures, dystrophin is expressed independently of fusion and of myosin heavy chain expression, and in some cases, expression is apparently enhanced by methylprednisolone. We suggest that dystrophin is a muscle-specific protein that does not require fusion for expression, and the methylprednisolone-induced enhancement of dystrophin expression may account for some of the clinical benefits of glucocorticoids in vivo. PMID- 8437701 TI - Psychogenic myoclonus. AB - We report 18 patients (13 women, 5 men; age range, 22 to 75 years; mean, 42.5), whom we ultimately diagnosed as having "psychogenic myoclonus." The myoclonus was present for an average of 36 months (range, 1 to 110), and it was segmental in 10, generalized in seven, and focal in one. Stress precipitated or exacerbated the myoclonic movements in 15 patients; 14 had a definite increase in myoclonic activity during periods of anxiety. A combination of the following findings helped to establish the psychogenic nature of the myoclonus: (1) clinical features incongruous with "organic" myoclonus, (2) evidence of underlying psychopathology, (3) an improvement with distraction in 14 and with placebo in nine, and (4) the presence of incongruous sensory loss or false weakness in five. Over half of all patients with adequate follow-up improved after gaining insight into the psychogenic mechanisms of their movement disorder. This study attempts to characterize psychogenic myoclonus, the most common psychogenic movement disorder in our movement disorders clinic, and provides a guide to its diagnosis and treatment. PMID- 8437702 TI - Transcranial Doppler assessment of cerebral perfusion reserve in patients with carotid occlusive disease and no evidence of cerebral infarction. AB - Using transcranial Doppler ultrasound (TCD), we measured bilateral middle cerebral artery mean blood flow velocities (MCAVs) before and 10 minutes after intravenous infusion of 1 gram of acetazolamide in 20 patients without cerebral infarction. Seven patients had normal carotid arteries (group 1), seven had unilateral internal carotid artery (ICA) stenosis > or = 75% (group 2), and six had unilateral ICA occlusion (group 3). Before acetazolamide infusion, side-to side differences in MCAV were 0.06 cm/sec in group 1 (p = 0.98), 4.3 cm/sec in group 2 (p = 0.36), and 15.0 cm/sec in group 3 (p = 0.02). Bilateral MCAV increased in all three groups after acetazolamide infusion, and the side-to-side differences in MCAV were 3.2 cm/sec in group 1 (p = 0.40), 11.4 cm/sec in group 2 (p = 0.04), and 27.6 cm/sec in group 3 (p = 0.03). Patients with carotid stenosis or occlusion and ipsilateral transient ischemic attacks (TIAs) had higher side-to side differences in MCAV before (p = 0.03) and after (p = 0.01) acetazolamide than did asymptomatic patients with carotid disease. The association of impaired cerebral perfusion reserve and TIAs suggests that the TCD-acetazolamide test may enable identification of a subgroup of patients with carotid occlusive disease who are at higher risk for stroke. PMID- 8437703 TI - Lack of a proprioceptive deficit after dorsal column lesions in monkeys. AB - Previous psychophysical examinations of the effects of dorsal column (DC) lesions on proprioception of the lower extremity have not revealed disturbances in proprioception, and there have been no similar experiments for the upper extremity. To evaluate the effect of DC lesions on upper extremity proprioception, we tested two monkeys with a variation of the typical clinical test for position sense. This test required the monkeys to detect the direction of a passive displacement of the finger. We identified proprioceptive deficits in one monkey following a DC lesion, but only when the finger was displaced with a small (< 14 degrees), slow (< 7 degrees/sec) movement. When we included displacements of all sizes and velocities in the analysis, performance was unaffected by the DC lesions in either monkey. Since the standard test for proprioception does not specify the speed and size of movements, we conclude that this test is not a valid method for estimating damage to the DCs. PMID- 8437704 TI - Pharmacodynamic modeling of oral levodopa: clinical application in Parkinson's disease. AB - We investigated the relationship between levodopa plasma concentration and the tapping effect, after a standard oral levodopa test, by kinetic-dynamic modeling in 40 parkinsonian patients with stable or fluctuating response to levodopa, and found no difference in levodopa plasma pharmacokinetics between stable and fluctuating patients. Conversely, levodopa equilibration half-life between plasma and effect-site concentration was five-fold shorter on average in fluctuating patients. Overall, levodopa equilibration half-life highly correlated with the duration of tapping response and provided a reliable quantitative index of central mechanisms that affect the length of clinical effect. Individual fitting of tapping measures to modeled drug effect-site concentrations by sigmoid Emax model revealed that fluctuating patients required almost two-fold higher levodopa concentrations (EC50) to elicit almost the same motor response (Emax). These findings suggest that shortening of levodopa clinical effect may be accompanied by a reduced drug affinity for the nigrostriatal dopaminergic system (EC50), with no change in its intrinsic activity (Emax). PMID- 8437705 TI - Loss of basic fibroblast growth factor in substantia nigra neurons in Parkinson's disease. AB - Basic fibroblast growth factor (bFGF) has a neurotrophic effect on mesencephalic dopaminergic neurons in vitro and in vivo. To explore whether an abnormality in bFGF expression occurs in Parkinson's disease (PD), we examined the substantia nigra (SN) of six PD and eight control cases immunohistochemically using a monoclonal antibody to bFGF. The mean number of melanin-positive neurons in sections of PD SN was 30.3% of the control mean, but the number of bFGF immunopositive neurons was only 4.7% of the control mean. bFGF-immunoreactivity was present in only 8.2% of PD, but in 93.7% of control melanin-positive neurons. These results suggest a profound depletion of bFGF in surviving dopaminergic neurons of the SN in PD, and this depletion may be related to the disease process. PMID- 8437706 TI - Primary T-cell lymphoma of the brainstem. AB - Most primary CNS lymphomas are non-Hodgkin's lymphomas of B-cell lineage. We report a case of a small lymphocytic-type T-cell lymphoma localized primarily to the brainstem and compare the characteristics of primary CNS T-cell lymphomas with those of primary CNS B-cell lymphomas. PMID- 8437707 TI - Nevus of Ota and leptomeningeal melanocytic lesions. AB - Two patients with congenital nevus of Ota developed intracranial malignant melanocytic tumors. One had a localized tumor that resembled a melanocytoma, but the other had a more highly malignant tumor that diffusely seeded the leptomeninges. There are 10 prior cases in the world literature. These cases are contrasted with the other disorders in which melanotic skin lesions are associated with CNS melanocytic tumors, including neurocutaneous melanosis, cellular blue nevus, and metastatic malignant melanoma. Each disorder tends to involve particular sites of the CNS. The nevus of Ota can be considered a neurocristopathy and, rarely, may give rise to malignant CNS lesions. PMID- 8437708 TI - Cortical somatosensory potentials evoked by magnetic stimulation of thoracic and lumbar roots. AB - We applied twin coil magnetic stimulation to thoracic and lumbar roots to evaluate the posterior column function in 50 normal subjects and 34 patients with neurologic disorders. In all nine patients with cervical myelopathy, there were abnormal somatosensory evoked potentials (SEPs) with stimulation of upper thoracic levels. In 14 patients with thoracic or lumbar myelopathy, there were normal SEPs with stimulation of spinal roots above the lesions and abnormal SEPs with stimulation below the lesions. In a patient with girdle sensation between T 3 and T-6, the peak latencies of P2 were significantly delayed with stimulation of T-2 and T-4, but peak latencies were normal with T-6, T-10, and L-3 stimulation. Ten patients with polyneuropathy had normal SEPs recorded with thoracic and lumbar root stimulation. SEPs by twin coil stimulation at thoracic and lumbar root levels are useful in detecting lesions of spinal cord or roots and for following their clinical course noninvasively. PMID- 8437709 TI - Sulfated glucuronyl glycolipids and gangliosides in the optic nerve of humans. AB - Pathologically delayed visual evoked potentials may be present in patients with neuropathy associated with IgM M-proteinemia, which is directed against myelin associated glycoprotein and sulfated glucuronyl glycolipids (SGGLs), but there are no reports of these antigens in the optic nerve. We recently examined human optic nerve and occipital lobe tissues for the occurrence of SGGLs using the technique of immunostaining on thin-layer chromatographic plates and found them in the optic nerve, but not the occipital lobe. SGGLs in the optic nerve may represent target antigens for CNS involvement by the M-protein in patients with neuropathy. We also studied the ganglioside composition of the optic nerve and found it different from that of the brain. Human optic nerve is characterized by an abundance of the b-series gangliosides, including GD1b, GT1b, and GQ1b. GD1a, which is usually a major component of brain gangliosides, is only a minor species of the optic nerve ganglioside fraction. PMID- 8437710 TI - Multiple cerebral hemorrhages in HTLV-I-associated myelopathy. AB - We describe a 66-year-old woman with long-standing HTLV-I-associated myelopathy who developed multiple parenchymal hemorrhages and whose angiogram suggested cerebral vasculitis. After cyclophosphamide and glucocorticoid therapy, both her acute deficits and chronic paraparesis improved. HTLV-I may be an etiologic agent in isolated angiitis of CNS. PMID- 8437711 TI - Frequent presence of anti-GQ1b antibody in Fisher's syndrome. AB - We used the enzyme-linked immunosorbent assay to investigate autoantibodies against the gangliosides GM1, GD1a, GD1b, GT1b, GD2, and GQ1b in sera from 16 patients with Fisher's syndrome. We found high anti-GQ1b antibody titers, mainly those of the IgG class, in the sera of 13 of these patients. The titers decreased with the clinical course of the illness. Moreover, anti-GQ1b antibody-positive patients had more severe ataxia of cerebellar type than the antibody-negative patients. PMID- 8437712 TI - Motor neuron diseases and amyotrophic lateral sclerosis: GM1 antibodies and paraproteinemia. AB - Six of 110 patients (5.5%) with forms of motor neuron disease had abnormal titers of GM1 antibodies of 1:1,600 or higher. Four others came with previously known high titers. Three patients with upper motor neuron (UMN) signs had titers of 1,600; those with probable or no UMN signs had higher titers. Nine patients had conduction block; six of them had abnormal antibody titers, four with 6,400 or higher. Therefore, patients with motor neuron disease and abnormal anti-GM1 titers may have UMN signs or conduction block. PMID- 8437714 TI - Hypertension and the risk of new-onset unprovoked seizures. AB - We tested the a priori hypothesis that hypertension can lead to seizures through vascular brain damage that might or might not involve manifest stroke. A case control study with 227 patients admitted for a first unprovoked seizure and 294 acute surgical controls was carried out at Harlem Hospital Center, New York City, between 1981 and 1984. History of hypertension was significantly associated with unprovoked seizures, even after adjustment for antecedent stroke and other potential confounders (adjusted odds ratio [OR] = 1.57; 95% confidence limit [CL], 1.0 to 2.44). There was marked synergism between history of stroke and history of hypertension; subjects with a history of both had a fourfold increase in seizure risk compared with subjects with neither (adjusted OR = 4.07; 95% CL, 1.50 to 11.0). In these data, history of hypertension appears to be an independent risk factor for new-onset unprovoked seizures, especially, but not only, in conjunction with a history of stroke. PMID- 8437713 TI - Nonketotic hyperglycinemia: clinical and electrophysiologic effects of dextromethorphan, an antagonist of the NMDA receptor. AB - A 10-week-old girl with nonketotic hyperglycinemia was treated with increasing amounts of dextromethorphan, an NMDA receptor antagonist. She improved neurologically; at 35 mg/kg/d, seizures ceased and EEG normalized. Dextromethorphan withdrawal resulted in a dramatic clinical deterioration coinciding with epileptic and high-voltage slow activity in the EEG. After reintroduction of dextromethorphan (35 mg/kg/d), recovery occurred within 24 hours. PMID- 8437715 TI - Abundant reinnervation in peripheral nerves in Joseph disease. AB - We performed coherent electromyographic studies in six patients with Joseph disease to determine whether there was collateral sprouting in peripheral nerves. An abundant reinnervation may partially explain why muscle strength is relatively preserved in Joseph disease. PMID- 8437716 TI - Aspiration in bilateral stroke patients: a validation study. AB - We validated the predictive accuracy of an "old" regression model in a "new" sample of bilateral stroke patients (N = 38). Abnormal gag reflex and impaired voluntary cough accurately predicted radiographically verified aspiration in both samples. A final model, using both samples, grouped patients into three risk strata: low risk of 14% (cough and gag normal), moderate risk of 46% to 51% (one of two behaviors abnormal); and high risk of 87% (cough and gag abnormal). PMID- 8437717 TI - Catatonic syndrome in acute severe encephalitis due to Borrelia burgdorferi infection. AB - We report a 19-year-old patient who presented with an acute encephalopathy manifested by catatonia. We isolated Borrelia burgdorferi from the CSF and demonstrated intrathecal production of IgG antibodies against B burgdorferi. The patient completely recovered after intravenous ceftriaxone therapy. PMID- 8437718 TI - Home ventilation for amyotrophic lateral sclerosis patients: outcomes, costs, and patient, family, and physician attitudes. AB - We conducted this study to better inform amyotrophic lateral sclerosis (ALS) patients about home ventilation and to assist them in decision-making. We gathered data on the prevalence of ALS patients on home ventilation in northern Illinois and the percentage who chose it, and we asked identified subjects, their families, and physicians for their attitudes toward home ventilation. Fewer than 10% of ALS patients had chosen home ventilation, and fewer than 5% were still on it. Seventeen patients (90%) were glad to have chosen home ventilation and would choose it again. Family caregivers reported major burdens, and only half would choose it for themselves. The mean yearly cost of home ventilation was $153,252. Home ventilation is effective for ALS patients had desired by the small number who undergo it, but it imposes significant burdens on families. PMID- 8437719 TI - Carbamazepine-related acute renal failure. PMID- 8437720 TI - Valine homozygous 129 PrP genotype in a French growth-hormone-related Creutzfeldt Jakob disease patient. PMID- 8437721 TI - AIDS and Chagas' disease. PMID- 8437722 TI - Leptomeningeal metastasis. PMID- 8437723 TI - ALS and eye movements. PMID- 8437724 TI - ALS and eye movements. PMID- 8437725 TI - Absence status. PMID- 8437726 TI - Visual cortical dysfunction. PMID- 8437727 TI - Parkinsonian tremor. PMID- 8437728 TI - Liver in Creutzfeldt-Jakob disease. PMID- 8437729 TI - Further cases of gas mask phobia. PMID- 8437730 TI - Utilization review. PMID- 8437731 TI - Al Eskan or pigeon breeder's disease? PMID- 8437732 TI - Chemical casualty decontamination by medical platoons in the 82d Airborne Division. AB - Chemical casualty decontamination must be carried out as far forward as possible to limit spread of agents and to render aid as quickly as possible. Traditionally, decontamination in the 82d Airborne Division has been provided by the Forward Support Medical Company. During Operation Desert Shield, the Division's Medical Platoons acquired the ability to decontaminate casualties for the first time. The author describes a detailed plan for casualty decontamination by Medical Platoons developed for this purpose. Dedicated rehearsal of decontamination and other aspects of chemical casualty care is essential. PMID- 8437733 TI - Loud noise and pregnancy. AB - Whether loud noise is harmful to the developing fetus and warrants removal of the pregnant woman from exposure remains ambiguous. The role of noise attenuation in utero in determining risk is discussed in this review. Reports in the medical literature have been frequently found to have confounders for human fetal development. Animal noise data are presented and their cautious extrapolation to humans is recommended. In summary, pregnant women should not unnecessarily be removed from the work force, and the Aeromedical Council may wish to establish policy for pregnant workers exposed to hazardous noise. PMID- 8437734 TI - Compatibility of army face paint and insect repellent formulation. AB - The compatibility studies of a new controlled-release repellent formulation (NSN 6840-01-284-3982, insect repellent personal application) and a new camouflage face paint (NSN 6850-01-262-0635) indicated that the repellent did not interfere with the use of face paints when repellent was applied first, and the face paints did not reduce the effectiveness of the repellent against mosquitoes. PMID- 8437735 TI - Effects of the Persian Gulf War on veterans with combat-related post-traumatic stress disorder. AB - The authors prospectively studied 32 male veterans with combat-related post traumatic stress disorder (PTSD) during the Persian Gulf War. The veterans were enrolled in a Veterans Affairs mental health clinic and met the DSM-III-R criteria for PTSD. The purpose of the study was to evaluate exacerbation and reactivation of PTSD symptomatology utilizing the Mississippi Scale and the Impact of Event Scale, two widely used self-report inventories for assessment of PTSD symptoms. Results did not support an increase in the PTSD symptoms of avoidance and intrusion during the actual combat period. Possible reasons for this finding are discussed. PMID- 8437736 TI - Lowering the cesarean rate at a small USAF hospital. AB - From July 1, 1988 to June 30, 1989, programs were initiated at the 93d Strategic Hospital at Castle AFB, California, to lower the cesarean (C/S) rate. Programs included vaginal birth after cesarean, external cephalic version, adequate labor documentation, and peer review of all C/S for fetal distress. One year prior (N = 467) was compared to the year after the start of these programs (N = 430). A significant decrease of 21.2% to 10.2% (p < 0.0001) was documented. We conclude that aggressive management of obstetrical patients can reduce the rate of C/S in a small USAF hospital without increasing maternal or neonatal risk. PMID- 8437737 TI - Predicting percent body fat from circumference measurements. AB - All U.S. Navy service members are required to meet percent body fat (%BF) standards as a condition of military service. Naval personnel who exceed standards for %BF can be separated from active duty. Currently, %BF predictions are determined by circumference measurements and a prediction equation (circumference equation = CEQ). In view of the importance these prediction results have for personnel retention, a validation study was undertaken to determine the accuracy of %BF prediction for a population determined to be overfat by the CEQ. The population for the validation study comprised men with 22%BF or greater and women with 30%BF or greater. Values for %BF were determined for 49 men and 50 women by hydrostatic weighing (HW) and circumference measurements at the Naval Submarine Medical Research Laboratory (NSMRL) using a regression equation developed at the Naval Health Research Center (NHRC), San Diego, California. The HW and CEQ values were compared to a superset of the original NHRC population. The correlation coefficients for the NSMRL validation group were lower than those reported in the original NHRC group. The results are attributed to the restricted range of NSMRL data and greater error of prediction at extreme ranges of values. A medical diagnostic model was used to evaluate the sensitivity, specificity, and predictive value of CEQ. It shows that the Navy's current procedures produce a 6.8 to 18% false positive rate for individuals declared as having excess body fat. The data suggest that caution should be utilized when using the CEQ method for individual career decisions. PMID- 8437738 TI - No longer destined to eat their young: satisfaction among Army family practice faculty. AB - In January 1987, all 63 faculty members at Army Family Practice Residencies received satisfaction questionnaires. Fifty-nine faculty (93.8%) responded with 40 (67.8%) being satisfied and 19 (32.2%) dissatisfied. Compared to faculty 7 years prior, these faculty are slightly older, have more practice experience, more opportunities for fellowship training, and are less likely both to have remaining mandatory military obligation and to leave the Army after 3 years. The key areas of faculty development, control over professional life, administration, and departmental goals and objectives truly discriminated satisfaction from dissatisfaction. A strategy to systematically develop potential faculty and reduce dissatisfaction is proposed. PMID- 8437739 TI - Satisfaction and dissatisfaction in institutional practice: results from a survey of U.S. military physicians. AB - Because of recent concerns about the professional satisfaction of physicians in general and of military physicians in particular, the authors surveyed a national sample of 1,392 military physicians; 88% responded. Two-thirds of physicians were at least somewhat satisfied with the professional abilities of their peers and with the quality of care they were able to provide, but only 19% were satisfied with salary and 27% with practice efficiency. Characteristics of physicians that were independently related to overall satisfaction included age, recruitment pathway, workload, specialty, and perceived availability of key resources. Indicator variables for the individual medical facilities were also significantly related to global satisfaction, suggesting a separate "hospital effect" that bears additional investigation. Efforts to improve satisfaction may enhance recruitment and retention of military physicians. PMID- 8437741 TI - Antecedent trauma and amyotrophic lateral sclerosis in young adult men. AB - Antecedent trauma has been implicated as a risk factor for many neurologic disorders, including amyotrophic lateral sclerosis (ALS). Aging is a dynamic, exponentially increasing risk factor for many disorders, also including ALS. Consequently, the relative significance of other risk factors diminishes correspondingly with increasing age. Gompertzian risk analysis suggests that only in a young susceptible individual could the age-dependent risk be low enough to relate the development of ALS to a non-age-dependent risk factor, such as preceding trauma. This point is illustrated by the case histories of three young adult men who developed ALS within 2 years following trauma. PMID- 8437740 TI - Results of a structured psychiatric interview to evaluate NASA astronaut candidates. AB - One hundred six astronaut applicants who had passed initial screening were evaluated for Axis I and Axis II DSM-III-R diagnoses using a structured psychiatric interview. Nine of 106 candidates (8.5%) met diagnostic criteria for six Axis I (including V-code), or Axis II disorders. The use of the NASA structured interview was effective in identifying past and present psychopathology in a group of highly motivated and healthy astronaut applicants. This was the first time that a structured interview had been used in such a setting for this purpose. The methodology described is applicable to any situation where the presence or history of psychopathology requires evaluation for job selection (e.g. pilot selection). PMID- 8437742 TI - Temporary thoracotomy wound closure following penetrating thoracic aorta injury. AB - On rare occasions, thoracic injuries require resuscitative efforts including emergent thoracotomy that result in edematous changes to the lungs and heart. Hemodynamic compromise occurs when these organs are placed in their anatomic position and closure of the thoracotomy is attempted. Adaptation of a temporary abdominal closure to a thoracic injury is described. PMID- 8437743 TI - Progressive wound closure with constant tension traction: combat theater application. PMID- 8437744 TI - Recalcitrant chylothorax and chylous ascites associated with hypothyroidism. AB - A patient with bilateral chylous effusions and chylous ascites resulting from mediastinal and periaortic radiation for Hodgkin's lymphoma is described. The chylothoraces were resistant to medical treatment as well as to surgical pleurectomy. The patient's medical condition worsened due to progression of the chylous effusions and an episode of catheter-related bacteremia complicated by respiratory failure requiring mechanical ventilation. While receiving mechanical ventilation, the patient was found to have hypothyroidism and was subsequently begun on thyroid hormone replacement therapy. Within 1 week, the chylous drainage from the pleural spaces dramatically decreased and eventually resolved. Eighteen months after beginning thyroid hormone replacement therapy, the patient continues to do well without recurrence of the chylous effusions. PMID- 8437745 TI - Reye's syndrome in a young adult. AB - Reye's syndrome (RS), originally known by the more descriptive name "encephalopathy with fatty degeneration of the viscera," was first described in children and is still seen mostly in them. However, there have been a few case reports of adult Reye's Syndrome (ARS) since the mid-1970s. The following report is a case of ARS in a previously healthy 26-year-old woman. Although the clinical description and the pathophysiology are well known in RS, the etiology and the pathogenesis are still far from clear. From available evidence a multifactorial cause seems likely, encompassing genetic susceptibility, environmental factors, and the convincing role of aspirin. Moreover, as there is increasing awareness of metabolic mimics, questions arise about the validity of some of the diagnoses of RS, even in Reye's original cases. PMID- 8437746 TI - Caring is not just what we do; it is who we are. PMID- 8437747 TI - Nursing is a basic service in our society. PMID- 8437748 TI - Untheorized dimensions of caring work: caring as a structural practice and caring as a way of seeing. PMID- 8437749 TI - The technology of caring: a synthesis of technology and caring for nursing administration. PMID- 8437750 TI - Caring for culturally diverse racial groups: an administrative matter. PMID- 8437751 TI - The microstory pathway of executive nursing rounds: tales of living caring. PMID- 8437752 TI - Nursing error and caring in the workplace. PMID- 8437753 TI - Caring in the time of AIDS: the importance of empathy. PMID- 8437754 TI - Caring for the caregivers: a wellness and renewal project. PMID- 8437755 TI - An ethical practice environment as a caring environment. PMID- 8437756 TI - An environment for care and service leadership: the nurse administrator's impact. PMID- 8437757 TI - Professional autonomy in nurses. PMID- 8437758 TI - What do young adolescent New Zealanders eat? Nutrient intakes of a nationwide sample of form 1 children. AB - AIM: To determine the nutrient intakes of a nationwide sample of form 1 children (aged 10-11 years), and to identify possible areas of nutritional concern. METHOD: Ten form 1 classes (322 children) were chosen as a nationally representative but nonrandom sample. A 24-hour dietary record was used to obtain quantitative information on all food and beverages consumed. Mean daily intakes were compared with Australian recommended dietary intakes (RDIs) for ages 8 to 11 years. Mean percentage contributions made by selected macronutrients to total energy intake, were compared to targets set for adult New Zealanders. RESULTS AND DISCUSSION: The final sample comprised 251 children (114 boys, 137 girls) aged 10 to 11 years. Mean energy intake was 8.32 MJ/d (boys) and 7.97 MJ/d (girls). These intakes were within the Australian recommended range for 10 to 11 year olds. Snacks contributed a mean of 30 percent to the daily energy intake of this sample. The mean percentage of daily energy from total fat was 36% (boys) and 35% (girls), close to the target set for adult New Zealanders. However, polyunsaturated fatty acids (PUFA) provided only 4% of mean daily energy compared to the 8% recommended for adults. Sugar intake was considered too high, with total sugars contributing one quarter of daily energy. This group would probably benefit from increased consumption of complex carbohydrate including fibre, and less refined sugar. Nearly half of the girls sampled had a calcium intake less than 70% of the Australian RDI. This result is of concern with respect to maintaining positive calcium balance for achievement of peak bone mass. Mean sodium intake was high at approximately 100 mmol/d, despite no information on salt added during cooking and before eating. Intake of zinc and vitamin B6 was considered to be too low with over one-third of the sample consuming less than 70% of the Australian RDI. PMID- 8437759 TI - Control of emesis associated with cancer chemotherapy. PMID- 8437760 TI - Nonspecific systolic murmurs: an audit of the clinical value of echocardiography. AB - AIM: To evaluate the clinical use of echocardiography in patients with nonspecific systolic murmurs. METHODS: Analysis of request forms and echocardiogram reports in a consecutive series of scans done for patients with nonspecific systolic murmurs between 1984 and 1991. RESULTS: Normal cardiac structure and function were found in: (1) 62% of 565 studies done for patients with nonspecific systolic murmurs; (2) 96% of 69 scans in patients with clinical diagnosis of a benign murmur and (3) 93% of 45 pregnant women with nonspecific systolic murmurs. No echocardiographic abnormalities were detected in 76% of studies done for patients aged between 1 and 50 yr. Congenital heart disease was found in 39% of patients with nonspecific systolic murmurs aged between 0 and 1 yr. Mitral regurgitation was found in 33% and aortic valve disease in 22% of nonspecific systolic murmurs patients aged over 60 yr. CONCLUSIONS: Echocardiography rarely revealed significant abnormalities in the assessment of patients with nonspecific systolic murmurs aged between 1 and 50 yr, especially when the test was used to confirm the clinical suspicion that the heart was normal. Ultrasound scanning was useful in the assessment of nonspecific murmurs in patients aged 0-1 yr or over 50 yr, particularly those over 60 yr. PMID- 8437761 TI - Pyloric stenosis: the Christchurch experience. AB - OBJECT: Evaluation of the performance of a general paediatric unit in diagnosis and treatment of infantile hypertrophic pyloric stenosis, including morbidity and measurable outcomes in relationship to changing management. METHODS: Retrospective case note audit. RESULTS: In the 11 year period 1980-91, 103 infants underwent surgical correction of pyloric stenosis, after correction of metabolic disturbance. There was a predominance of males (82.5%), but the incidence of first born infants affected was no greater than the population birth order. While the clinical diagnosis was firm in the majority of infants, over 75% had at least one radiologic imaging procedure. On objective criteria, 80% of patients were less than 5% dehydrated, despite having electrolyte and acid-base derangement. The relatively high incidence of mucosal perforation (31.1%) did not lead to further morbidity. The incidence of postoperative vomiting (19.4%) was significantly less than in previously reported series. There were no deaths, one patient suffered longterm neurologic deficit following profound hypoglycaemia. A change in preoperative management to aggressive rehydration did not reduce morbidity, and was associated with an increased median postoperative stay. CONCLUSIONS: Pyloric stenosis remains a relatively common surgical problem of infancy. The cornerstone of diagnosis remains a clinical one; however there is a place for radiology. Operative repair is elective, following correction of metabolic derangement. In a general paediatric unit, long term sequelae of initial morbidity are rare. PMID- 8437762 TI - Maori attitudes to diabetes and diabetes health care delivery in north Canterbury. AB - AIMS: The study aims were as follows: (1) To obtain information regarding Maori attitudes to diabetes and to the services provided by a specialist diabetes clinic in Christchurch; (2) to initiate discussion about local diabetes health care delivery for Maori. METHODS: A questionnaire was designed following advice from professional Maori health researchers, with the aim of assessing Maori attitudes to diabetes and specialist diabetes services, available in Christchurch. RESULTS: The questionnaire was delivered to 51 (77%) of the 66 Maori with noninsulin dependent diabetes (NIDDM), attending a specialist diabetes clinic in Christchurch. Although 47 of the 51 subjects were able to name one or more diabetes complications, only five subjects named heart disease as a complication, despite the fact that heart disease is a major cause of mortality in NIDDM: Subjects were selected on the basis of being hospital specialist clinic attenders and the majority were satisfied with currently available services, yet 10 of the 51 subjects indicated that they would prefer marae-based to hospital based diabetes health care, if they had a choice. CONCLUSIONS: The process of questionnaire interview and dissemination of results proved to be a cost effective means of initiating local discussion about future directions for Maori diabetes health care delivery. PMID- 8437763 TI - Psoriasis: therapeutic aspects. AB - Some of the more common features of psoriasis are reviewed here as an introduction to therapeutic modalities that can be employed in the management of this disorder in the New Zealand situation. An approximate indication of costs for the various therapies is included. This article is sponsored by the therapeutics section of the Department of Health, however, the views of the contributors do not necessarily reflect departmental policies. PMID- 8437764 TI - Herpes simplex encephalitis. PMID- 8437765 TI - Volunteer service abroad. PMID- 8437766 TI - Current affairs programmes and RHA purchasing. PMID- 8437767 TI - Predicted values for peak flow rates. PMID- 8437768 TI - Feeling better, costing less. PMID- 8437769 TI - Contracting quality health care. PMID- 8437770 TI - Missing patients in general practice; the computerised age-sex register. PMID- 8437771 TI - NZMA patient information pamphlet on child sexual abuse. PMID- 8437772 TI - Vitamin K prophylaxis in the newborn. PMID- 8437773 TI - Health reforms. PMID- 8437774 TI - AIDS. PMID- 8437775 TI - The common problem of vulvar pruritus. PMID- 8437776 TI - Subchorionic hematoma: a review. AB - A review of the English literature on subchorionic hematoma (SCH) is presented. Fourteen studies are reviewed. The incidence of SCH varied greatly among studies from 4 to 48 per cent. Small SCH tend to be more common in the first trimester and appear to pose no added risk to the ongoing pregnancy. Conversely, SCH in the second trimester often are larger and may be associated with an increased risk of preterm delivery. The etiology of these hematomas remains unclear. Pathological changes that might contribute to their formation are reviewed. Larger studies with controls, including data on the incidence of SCH in a population of normal obstetric patients are needed. PMID- 8437777 TI - Chronic pelvic pain in women: toward an integrative model. PMID- 8437778 TI - The prostaglandin synthesis inhibitor ketorolac blocks ritodrine-stimulated production of prostaglandin F2 alpha in pregnant sheep. AB - OBJECTIVE: To determine whether ritodrine-stimulated production of prostaglandin (PG) F2 alpha by pregnant uterine tissues can be blocked by the concurrent administration of ketorolac, a PG synthesis inhibitor. METHODS: We infused saline, ritodrine, ketorolac, or a combination of ritodrine and ketorolac into chronically catheterized pregnant sheep. Concentrations of PGF2 alpha in uterine venous plasma were measured by radioimmunoassay at 0, 1, 2, 3, 4, and 24 hours during the infusions. RESULTS: Ritodrine significantly increased uterine venous PGF2 alpha; mean percent increases at 4 hours were 330% and 380%, and at 24 hours 370%, compared with controls. During concurrent ritodrine and ketorolac infusion, there was no increase in uterine venous PGF2 alpha at any time. CONCLUSIONS: Ketorolac completely blocks ritodrine-stimulated production of PGF2 alpha in pregnant uterine tissues. We conclude that ritodrine stimulates PG production through mobilization of arachidonic acid, and this can be effectively blocked with a PG synthesis inhibitor. This finding may have important clinical applications in the treatment of preterm labor. PMID- 8437779 TI - Production of prostacyclin and thromboxane in lupus pregnancies: effect of small dose of aspirin. AB - OBJECTIVES: To find out whether the tendency toward poor outcome in lupus pregnancies could be explained by changes in prostacyclin/thromboxane production, to relate these changes to the presence of antiphospholipid antibodies, and to study the potential benefits of low-dose aspirin. METHODS: We followed the urinary output of prostacyclin metabolites (6-keto-prostaglandin [PG]F1 alpha, 2,3-dinor-6-keto-PGF1 alpha) and thromboxane metabolites (thromboxane B2, 2,3 dinor-thromboxane B2) using high-pressure liquid chromatography followed by radioimmunoassay. We studied 14 pregnant women with systemic lupus erythematosus (SLE), of whom six had detectable antiphospholipid antibodies. The patients were randomized by a computerized program to receive either 50 mg aspirin daily (six women) or placebo (eight women). Nine healthy pregnant women served as controls. RESULTS: The production of prostacyclin was normal in early pregnancy in SLE patients but was reduced during late gestation in those without antiphospholipid antibodies. The production of thromboxane was increased in SLE patients compared with controls, and this increase was highest (two-to threefold rise) when antiphospholipid antibodies were detectable. Aspirin eliminated thromboxane dominance without affecting prostacyclin production. CONCLUSION: These data suggest that the presence of antiphospholipid antibodies in SLE patients may trigger thromboxane dominance, possibly contributing to the adverse outcome of these pregnancies. This thromboxane dominance can be eliminated with aspirin. PMID- 8437780 TI - Labor induction with the prostaglandin E1 methyl analogue misoprostol versus oxytocin: a randomized trial. AB - OBJECTIVE: To compare the safety and efficacy of intravaginal misoprostol versus intravenous (IV) oxytocin infusion for labor induction. METHODS: One hundred thirty patients were randomly assigned to one of two induction groups: 1) intravaginal misoprostol or 2) IV oxytocin by continuous infusion, with prior cervical ripening using prostaglandin (PG) E2 gel if necessary. RESULTS: Among 129 patients evaluated, 64 were allocated to the misoprostol group and 65 to the oxytocin group. Prostaglandin E2 gel was administered to 29 patients (45%) in the oxytocin group with unripe cervices. Uterine tachysystole occurred more frequently in patients in the misoprostol group (34.4%) than in the oxytocin group (13.8%) (P < .05). Nevertheless, no statistically significant differences were noted between the groups in intrapartum complications including uterine hyperstimulation syndrome, mode of delivery, and neonatal or maternal adverse outcomes. The interval from induction to vaginal delivery was significantly shorter in the misoprostol group (11 versus 18 hours; P = .004). In 74% of patients in the misoprostol group, only one intravaginal dose was required for successful labor induction. CONCLUSIONS: Intravaginal administration of misoprostol safely and effectively induces labor while minimizing the expense associated with IV oxytocin infusion. The higher frequency of uterine tachysystole associated with the use of misoprostol did not increase the risk of adverse intrapartum or perinatal outcomes. The use of PGE2 gel for cervical ripening contributed to the longer induction-to-vaginal delivery interval noted in the oxytocin group. Clinical trials appear warranted to detail misoprostol's optimal route, dose, and schedule for labor induction and its safety. PMID- 8437781 TI - Altered lipid composition, increased lipid peroxidation, and altered fluidity of the membrane as evidence of platelet damage in preeclampsia. AB - OBJECTIVE: To assess lipid composition, lipid peroxidation, and fluidity of the membrane of platelets from preeclamptic women. METHODS: We studied 40 primigravid women at 28-32 weeks' gestation; 20 were preeclamptic and 20 were normotensive. After preparing platelet membranes, we extracted lipids, measured cholesterol and phospholipid concentrations, and calculated the proportion of unsaturated to saturated fatty acids. Lipid peroxides expressed as conjugated dienes were determined by spectrophotometry. Membrane fluidity was determined by means of fluorescent lipophilic probes. Statistical analysis was performed by the Student t test, with significance at P < .05. RESULTS: Cholesterol concentration, cholesterol-to-phospholipid ratio, the amount of unsaturated fatty acids, conjugated dienes, and membrane fluidity significantly increased in platelets from preeclamptic patients as compared with the normotensive women. CONCLUSIONS: The discrepancy between cholesterol increase and membrane fluidity increase is consistent with the increase in unsaturated fatty acid content. In the platelet membrane, unsaturated fatty acids constitute the larger substrate for lipid oxidation and can also take part in the formation of thromboxane. Therefore, platelet membrane damage in preeclampsia, through imbalance of thromboxane A2/prostacyclin production, may contribute to the onset or maintenance of vasoconstriction and hypertension. PMID- 8437782 TI - Fetal growth in patients with elevated maternal serum hCG levels. AB - OBJECTIVE: To determine the relationship between maternal serum hCG levels and small for gestational age (SGA) infants. METHODS: Maternal serum hCG levels were measured in 638 consecutive pregnant women in whom gestation was dated by crown rump length and who later delivered a singleton infant. Fetal growth was compared between the women with elevated maternal hCG (above 2 multiples of the median) and those with normal levels. RESULTS: Elevated maternal hCG values were found in 6.6%, of whom 19% delivered SGA infants. In the normal maternal hCG group, 3.9% of the infants were SGA. These differences were statistically significant by chi 2 analysis. Mothers with elevated hCG also had a significantly higher risk for fetal death, preterm rupture of the membranes, and abruptio placentae by the Fisher exact probability test. CONCLUSION: Elevated maternal serum hCG levels correlate with SGA infants. PMID- 8437783 TI - Glucose tolerance test: degree of glucose abnormality correlates with neonatal outcome. AB - OBJECTIVE: To determine how well the extent of glucose abnormality, as reflected by the number of abnormal values on the 3-hour oral glucose tolerance test (GTT), correlates with the level of carbohydrate intolerance during pregnancy and with the severity of adverse outcome. METHODS: We followed 764 gestational diabetic women under a once-per-week fasting and 2-hour postprandial serum glucose monitoring system. The subjects were stratified by the number of abnormal values on their GTTs. The level of glucose control and incidence of large for gestational age (LGA) infants were then determined and compared with the findings in 636 gravidas with abnormal screening but all normal GTT values. RESULTS: Patients with one or more abnormal GTT values had comparable incidences of LGA infants, which were all significantly greater than that in the 0-abnormal group (23-27% versus 13%; P < .01). This difference was due to subjects with poor glucose control. The means of the GTT values for each sampling time were greater and the GTT periodicity (the time for the GTT curve to return to the fasting level) was longer with an increasing number of GTT abnormal values (zero versus one versus two versus three versus four abnormal values, P < .02). The mean fasting, 2-hour postprandial, and overall mean glucose values during the study were positively associated with the number of abnormal GTT values. CONCLUSIONS: One or more abnormal GTT values were associated with comparably elevated incidences of LGA infants in patients with poor glycemic control. Achievement of recommended glucose control decreased adverse outcomes to near normal levels. PMID- 8437784 TI - Perinatal outcome in hypothyroid pregnancies. AB - OBJECTIVE: To relate hypothyroidism to perinatal outcome. METHODS: A cohort of 68 hypothyroid patients with no other medical illnesses was divided into two groups according to the initial thyroid function tests. The first group had 23 women with overt hypothyroidism, and the second had 45 subjects with subclinical hypothyroidism. We sought to identify the pregnancy outcomes of gestational hypertension, low birth weight, fetal death, congenital anomalies, maternal anemia, and postpartum hemorrhage. RESULTS: Gestational hypertension--namely, eclampsia, preeclampsia, and pregnancy-induced hypertension--was significantly more common in the overt and subclinical hypothyroid patients than in the general population, with rates of 22, 15, and 7.6%, respectively. In addition, 36% of the overt and 25% of the subclinical hypothyroid subjects who remained hypothyroid at delivery developed gestational hypertension. Low birth weight in both overt and subclinical hypothyroid patients was secondary to premature delivery for gestational hypertension. Except for one stillbirth and one case of clubfeet, hypothyroidism was not associated with adverse fetal and neonatal outcomes. CONCLUSION: Normalization of thyroid function tests may prevent gestational hypertension and its attendant complications in hypothyroid patients. PMID- 8437785 TI - Anonymous cocaine screening in a private obstetric population. AB - OBJECTIVE: To establish the prevalence of cocaine use in private obstetric patients during their prenatal care and at admission to delivery units. METHODS: Urine samples were collected anonymously during routine sampling from 1425 patients in six private hospitals and four private physicians' offices. RESULTS: Positive cocaine metabolites were identified in three of 555 urine specimens (0.54%) obtained from hospitals and in two of 870 (0.23%) obtained from private offices during prenatal examinations. The total positive urine cocaine results were five of 1425 (0.35%). CONCLUSIONS: Universal screening in a private obstetric population similar to that found in Denver would not be cost-effective. We urge health care providers to ask patients about substance abuse and to screen patients who are at high risk for substance use. PMID- 8437786 TI - Sexuality after hysterectomy: a factor analysis of women's sexual lives before and after subtotal hysterectomy. AB - OBJECTIVE: To study the effect of subtotal hysterectomy on a woman's sexuality. METHODS: One hundred four women were interviewed 1 month before and 1 year after surgery. Data concerning their sexuality before and after the operation were evaluated using a multivariate method. RESULTS: Half of the women reported improvement in their sexuality after surgery and 21% reported deterioration. There were only small changes in sexual variables: Frequency of cyclicity of sexual desire was reduced, coital frequency increased, and frequency of desire, frequency of orgasm, and multiplicity of orgasm were unchanged for the entire series. The best predictive factors for sexuality after surgery were presurgical coital frequency, cyclicity of arousability, frequency of desire, and frequency of orgasm. Multiplicity of orgasm, cyclicity of desire, and attitude to the sexual partner also correlated with postoperative sexuality. Preoperative deep dyspareunia had a small influence, although 83% (48 of 58) with deep dyspareunia experienced relief after the operation. Preoperative deterioration of desire and coital activity had no correlation to sexuality after surgery. CONCLUSION: Preoperative sexual activity is more important in predicting postoperative sexuality than is the occurrence of dyspareunia or deterioration of sexual activity because of uterine disease. PMID- 8437787 TI - Hysterectomy, oophorectomy, and subsequent ovarian cancer risk. AB - OBJECTIVE: To analyze the relation between hysterectomy with or without oophorectomy and the risk of subsequent ovarian cancer. METHODS: We have conducted a case-control study since 1983 in a network of general and university hospitals in the greater Milan area. The cases were 953 women aged less than 75 years with histologically confirmed epithelial ovarian cancer. Women younger than 75 years residing in the same geographic area and admitted for acute conditions to the same network of hospitals where the cases had been identified were eligible as controls. Potential controls were excluded if they had been admitted for gynecologic, hormonal, or neoplastic diseases or had previously undergone bilateral oophorectomy. A total of 2758 controls were interviewed. RESULTS: Fifty two cases (5.5%) and 215 controls (7.8%) reported a history of hysterectomy, including eight cases and 38 controls who also reported unilateral oophorectomy. In comparison with women with intact uterus and ovaries, the age-adjusted relative risk (RR) was 0.7 in both women who reported hysterectomy alone (95% confidence interval [CI] 0.5-0.9) and in those reporting hysterectomy plus unilateral oophorectomy, though the latter finding was not statistically significant (95% CI 0.3-1.4). The risk of ovarian cancer was inversely related with time from hysterectomy. Compared with women reporting no pelvic surgery, the RR was 0.9 (95% CI 0.4-1.7), 0.7 (0.3-1.6), 0.7 (0.3-1.4), and 0.5 (0.3-0.8), respectively, in women reporting hysterectomy within 4 years or less and 5-9, 10 14, and 15 years or more before interview. CONCLUSION: Hysterectomy approximately halves the risk of ovarian cancer, possibly because of altered ovarian blood flow or the opportunity that hysterectomy provides for examining the ovaries. PMID- 8437788 TI - Flow cytometric evaluation of early invasive cervical cancer. AB - OBJECTIVE: To define the role of flow cytometry as a prognostic indicator in early cancers of the uterine cervix. METHODS: Flow cytometry was used to determine ploidy, DNA index, and S-phase fraction on 141 samples from the tumors of 53 women with stage IB cancers of the cervix treated by radical hysterectomy and pelvic lymphadenectomy as primary therapy. Multiple samples of the same tumor were analyzable for 47 (89%) of the subjects. One-way analysis of variance for the multiple samples was used to compare the heterogeneity of flow cytometry data, both within each tumor and between patients. Flow cytometry results, as well as previously described clinical and pathologic prognostic factors, were correlated to recurrence and survival using Cox regression hazard ratios and Kaplan-Meier estimates. RESULTS: We found DNA aneuploidy in 25 (47%) of the cancers, with a mean (+/- standard error) DNA index of 1.52 +/- 0.07. The mean S phase fraction was 7.6 +/- 0.4% for diploid tumors and 9.2 +/- 0.4% for aneuploid tumors. The cancers from 24 women (45%) were homogeneously diploid, 18 (34%) were consistently aneuploid, and five (9%) had mixed diploid/aneuploid samples. Analysis of variance of the multiple samples for each woman revealed a greater standard deviation (SD) between patients than within any individual tumor for both DNA index (ratio of between SD to within SD 2.1; P < .0001) and S-phase fraction (ratio 1.6; P < .0001). Of the previously described clinical and pathologic prognostic factors, only depth of invasion, expressed as either percent of cervical wall thickness or as thirds, was correlated with recurrence or survival. Neither the DNA index nor S-phase fraction correlated significantly with recurrence or survival. CONCLUSIONS: These results suggest that alterations in the DNA content or proliferative activity of early invasive cancers of the uterine cervix do not reflect biologic behavior in terms of recurrence or survival, and that this behavior is not due to tumor heterogeneity. PMID- 8437789 TI - Women with human immunodeficiency virus infection and abnormal Papanicolaou smears: a prospective study of colposcopy and clinical outcome. AB - OBJECTIVE: To determine the effect of human immunodeficiency virus (HIV) infection on colposcopic and histologic findings and clinical outcome in women who have abnormal Papanicolaou smears. METHODS: We conducted a prospective study of women with abnormal Papanicolaou smears from among those participating in a longitudinal study of HIV infection, human papillomavirus infection, and genital neoplasia. Women with squamous intraepithelial lesions (SIL) on blindly interpreted Papanicolaou smears were referred for colposcopy and standard gynecologic care. Colposcopic and histologic findings were correlated with cytology, and differences between HIV seropositives and seronegatives were analyzed. RESULTS: Thirty-eight of 48 women referred underwent colposcopy, of whom 36 (94.7%) had colposcopic or histologic findings no more severe than those suggested by Papanicolaou smear. Seventeen of 25 HIV seropositives (68%) had cervical or vaginal condyloma or neoplasia, compared with three of 13 seronegatives (23%) (odds ratio [OR] 7.1, 95% confidence interval [CI] 1.5-33.0). Among seropositives, seven (28%) had cervical intraepithelial neoplasia (CIN) grade II or III; ten (40%) had cervical or vaginal condyloma, CIN I, or both; and eight (32%) had no vaginal or cervical SIL. There was no case of invasive carcinoma. Seven seropositives (28%) had or developed multicentric disease, compared with no seronegatives (P = .07). Follow-up ranged at 3-37 months and showed that all three treated seronegative women and five of ten treated seropositive women had normal examinations. Three seropositive patients had persistent disease without progression, and two had progression of condyloma. No CIN II, CIN III, or invasive carcinoma was seen during follow-up. CONCLUSIONS: Among women seropositive for HIV who had SIL on a Papanicolaou smear, colposcopic and histologic findings were predicted reliably by the cytologic smear. Rapid progression of CIN after standard gynecologic care for early genital lesions was not seen. PMID- 8437790 TI - Comparison of persistent ectopic pregnancy after laparoscopic salpingostomy versus salpingostomy at laparotomy for ectopic pregnancy. AB - OBJECTIVE: To compare persistent ectopic pregnancy after laparoscopic salpingostomy versus salpingostomy at laparotomy for the treatment of intact ampullary ectopic pregnancy. METHODS: We reviewed the medical records of 157 patients who had undergone salpingostomy for intact ampullary ectopic pregnancy at Yale-New Haven Hospital between September 1, 1986 and August 31, 1991. One hundred three women had laparoscopic salpingostomy and 54 had salpingostomy at laparotomy. RESULTS: Sixteen of 103 women (15.5%) undergoing laparoscopic salpingostomy were treated for persistent ectopic pregnancy, in contrast to one of 54 women (1.8%) who had salpingostomy by laparotomy. The adjusted odds ratio for persistent ectopic pregnancy after laparoscopic salpingostomy versus salpingostomy at laparotomy for an intact ampullary ectopic pregnancy was 8.4, with 95% confidence interval 1.1-62 (P < .02). Stepwise logistic regression demonstrated that a laparoscopic approach to salpingostomy (P < .05), smaller ectopic size (P < .01), and fewer days of amenorrhea (P < .05) predicted persistent ectopic pregnancy. CONCLUSION: Persistent ectopic pregnancy is more likely after laparoscopic salpingostomy than after salpingostomy at laparotomy for intact ampullary ectopic pregnancy. PMID- 8437791 TI - The microbiology of post-cesarean wound morbidity. AB - OBJECTIVE: To determine the microbiology of wound morbidity following cesarean deliveries. METHODS: Nine hundred thirty-nine wounds in post-cesarean patients were followed prospectively. Aspirates from the abdominal incision were collected if the wounds developed erythema, induration, or pain and had demonstrable fluid collection noted on ultrasound. Cultures were also obtained of wound exudates when there was spontaneous separation of the skin. Gram stains were performed concomitantly with culture. RESULTS: The cumulative incidence of post-cesarean wound morbidity between September 1990 and June 1991 was 6.9% (65 of 939), and the rate of culture-positive wounds was 72% (47 of 65). Ureaplasma urealyticum was the most frequent isolate at a rate of 62% (29 of 47), followed by coagulase negative staphylococci at 32% (15 of 47) and Enterococcus faecalis at 28% (13 of 47). Gram stains of the exudates obtained were used to predict microbiologic results. Organisms present on Gram stain yielded a sensitivity of 0.55, specificity of 1.0, positive predictive value of 1.0, and negative predictive value of 0.71 when used to predict positive culture results for bacterial wound infection other than with genital mycoplasmas. White blood cell counts greater than ten per 400x high-power fields yielded a sensitivity of 0.83, specificity of 0.72, positive predictive value of 0.89, and negative predictive value of 0.62 when used to predict wound infection including genital mycoplasmas. CONCLUSIONS: Genital mycoplasmas are the most prevalent bacterium in post-cesarean wound infections in this population. If genital mycoplasmas are pathogenic in this setting, then the Gram stain may be useful in predicting wound microbiology. More research is needed on the pathogenic role of genital mycoplasmas in wound infections. PMID- 8437792 TI - Reduction in very low birth weight deliveries and perinatal mortality in a specialized, multidisciplinary twin clinic. AB - OBJECTIVE: To determine whether a specialized, multidisciplinary twin clinic could reduce rates of very low birth weight (VLBW) and perinatal mortality. Multifetal gestations account for only 1% of all pregnancies, yet are responsible for nearly 10% of all perinatal mortality. Very low birth weight (less than 1500 g) infants are the major contributors to this increased perinatal mortality rate. METHODS: Eighty-nine twin pairs followed in the Twin Clinic since 1988 were compared with 51 contemporary twin pairs who did not attend the Twin Clinic. Patients not attending the Twin Clinic were attended in the high-risk clinic by the obstetric residents and faculty. All maternal transports were excluded. Aspects of prenatal care emphasized in the Twin Clinic that differed from the high-risk clinic included consistent evaluation of maternal symptoms and cervical status by a single certified nurse-midwife, intensive preterm birth prevention education, individualized modification of maternal activity, increased attention to nutrition, and tracking of clinic non-attenders. RESULTS: There were no differences between the groups in demographic characteristics, adequacy of prenatal care, or antepartum complications. However, Twin Clinic attenders had lower rates of VLBW infants, neonatal intensive care unit admission, and perinatal mortality. CONCLUSIONS: These improvements in perinatal outcome for twin gestations are attributed to intensive preterm birth prevention education, individualization of prenatal care, and frequent maternal assessment by a consistent care provider. This approach reduced the rate of very early preterm delivery and its neonatal sequelae. PMID- 8437793 TI - Iatrogenic respiratory distress syndrome following elective repeat cesarean delivery. AB - OBJECTIVE: To determine the incidence of iatrogenic respiratory distress syndrome (RDS) following elective repeat cesarean delivery and to identify whether it was associated with departures from accepted management guidelines. METHODS: Between January 1986 and March 1991, there were 23,125 deliveries at Northwestern Memorial Hospital, of which 1207 were repeat cesarean births without labor. During this period, 18 neonates of 37 weeks' gestation or greater or 2500 g or greater who were delivered by elective repeat cesarean were admitted to the neonatal intensive care unit (NICU) for respiratory difficulties. RESULTS: Five of the 18 neonates admitted to the NICU with respiratory difficulty following elective repeat cesarean delivery met the criteria for RDS. This represents an incidence of 0.41% (five of 1207), or one case of RDS for every 241 repeat cesarean deliveries without labor. Four of the five neonates required mechanical ventilation for an average of 6.8 days. The average NICU stay was 11.2 days. Complications included pneumothorax (one) and pulmonary hemorrhage (one). Departures from accepted management guidelines included a discrepancy between ultrasound and menstrual dates (two), no confirmation of menstrual dates (one), and delivery before 39 weeks' gestation (two). CONCLUSION: Iatrogenic RDS continues to occur in the setting of elective repeat cesarean delivery and is associated with a failure to adhere to clinical protocols. PMID- 8437794 TI - Maternal tobacco use and substance abuse: reported prevalence rates and associations with the delivery of small for gestational age neonates. AB - OBJECTIVE: To determine the changes in reported prevalence rates of tobacco use and substance abuse in a population of pregnant women, as well as to evaluate the associations between such use and sociodemographic characteristics and the delivery of small for gestational age (SGA) neonates. METHODS: We studied 7741 women who delivered at Cedars-Sinai Medical Center from 1986-1990. Antenatal and delivery information was entered prospectively into the computerized perinatal data base. Subjects were classified according to tobacco use and substance abuse status. We defined SGA as a birth weight less than the tenth percentile for gestational age at delivery. Univariate and multivariate analyses were used to determine the associations between SGA and tobacco use, substance abuse, and sociodemographic characteristics. RESULTS: We found that the reported prevalence rates of tobacco use and substance abuse declined between 1986-1990 (10 versus 6% and 7 versus 2%, respectively; P < .001). Tobacco use and substance abuse were reported as being highest in black women (11 and 6%) and lowest in Asian and Hispanic women (4 and 3%), a significant difference (P < .001). Tobacco use and race-ethnicity were found to have the strongest independent associations with SGA. The incidence of SGA was highest in black women identified as tobacco users and substance abusers. CONCLUSIONS: The reported rates of tobacco use and substance abuse varied by year, race-ethnicity, and insurance status. There were significant associations between maternal tobacco use, substance abuse, and race ethnicity and the incidence of SGA neonates. PMID- 8437795 TI - Detection of human parvovirus B19 in early spontaneous abortuses using serology, histology, electron microscopy, in situ hybridization, and the polymerase chain reaction. AB - OBJECTIVE: To determine whether there is an association between parvovirus B19 infection and early spontaneous abortion at less than 20 weeks' gestation. METHODS: Eighty samples of early spontaneous abortions were analyzed. Each sample was examined histologically for the presence of viral inclusions, and selected cases were analyzed for parvovirus using electron microscopy and in situ hybridization. Polymerase chain reaction DNA amplification for the virus was done in each case. Maternal sera were analyzed for immunoglobulin (Ig) M and IgG parvovirus antibodies and compared with temporally matched controls. RESULTS: Five cases in the study group had evidence of seroconversion for parvovirus, compared with two controls. Products of conception from two of these five cases were positive for virus by polymerase chain reaction amplification, and only one of these two had a characteristic inclusion of parvovirus histologically. Conversely, five chorionic vesicles from mothers who had not seroconverted had histologic changes suggesting parvovirus infection, but all of these cases were negative for parvovirus using in situ hybridization, polymerase chain reaction, and electron microscopy. CONCLUSIONS: Parvovirus B19 DNA was found in two of 80 early spontaneous abortuses. Although viral DNA was detected in two cases, there was no clear evidence that the infections caused fetal death. Neither case showed erythroblastosis with large numbers of inclusions, as is seen in hydropic fetuses with parvovirus infection. In addition, in five cases in which parvovirus infection was not documented serologically or by the polymerase chain reaction, there was erythroid nuclear clearing suggestive of parvovirus B19 inclusions. This indicates that histologic evaluation for parvoviral inclusions is not always reliable in early spontaneous abortuses. PMID- 8437796 TI - Non-coiled umbilical blood vessels: a new marker for the fetus at risk. AB - OBJECTIVE: To evaluate the perinatal outcomes of fetuses born with non-coiled umbilical blood vessels. METHODS: We performed a prospective study of umbilical cords that lacked umbilical vascular coiling. The perinatal outcomes were compared with those of neonates born with coiled umbilical blood vessels. RESULTS: Thirty-eight (4.3%) of 894 fetuses were born with non-coiled umbilical vessels. The non-coiled group had a significantly increased incidence of intrauterine death (P = .009), preterm delivery (P = .006), repetitive intrapartum fetal heart rate decelerations (P < .00005), operative delivery for fetal distress (P < .00005), meconium staining (P = .007), and anatomical karyotypic abnormalities (P = .03). CONCLUSIONS: Our findings suggest that the fetus with non-coiled (ie, straight) umbilical blood vessels is at increased risk for perinatal morbidity and mortality. Non-coiled umbilical vessels may represent a pathologic developmental process that places the fetus at risk. Moreover, absence of the normal coiled umbilical configuration may result in a cord that is structurally less able to resist external compressive forces. PMID- 8437797 TI - Fetal hemivertebrae: associated anomalies, significance, and outcome. AB - OBJECTIVE: To study fetuses who had the sonographic diagnosis of hemivertebrae made in utero (excluding open neural tube defects) and to determine the incidence of associated anomalies, karyotypes, and neonatal outcome. METHODS: Twenty-seven fetuses with sonographically detected vertebral abnormalities (excluding neural tube defects) and postnatal follow-up were included in the study. Associated structural defects and karyotypic anomalies were tabulated. The outcome for fetuses with isolated vertebral abnormalities on prenatal sonogram was compared with that of fetuses with associated anomalies. RESULTS: Eleven of 27 fetuses had hemivertebrae as the only sonographic anomaly. Nine of the 11 were live-born with a good outcome; one patient elected pregnancy termination, and one fetus died of sepsis after premature rupture of the membranes. Sixteen fetuses had other anomalies including cardiac, intestinal, renal, intracranial, and limb anomalies. Seven of these 16 had Potter syndrome, two of whom also had sacral agenesis. Only five of those with additional anomalies survived; five died and six pregnancies were electively terminated. Because four of the six aborted fetuses had Potter syndrome (renal dysgenesis), a lethal malformation, a total of at least nine of the 16 fetuses with other anomalies would not have survived. All seven fetuses with severe oligohydramnios had lethal anomalies. Eighteen fetuses underwent karyotyping (including all those with isolated vertebral anomalies), and all had normal karyotypes. CONCLUSION: Our study suggests that sonographically diagnosed, isolated fetal vertebral anomalies carry a good prognosis and the likelihood of a normal karyotype. The presence of associated anomalies reduces the survival to 50%, and when accompanied by significant oligohydramnios, the mortality is 100%. PMID- 8437798 TI - Racial comparisons and contrasts in urinary incontinence and pelvic organ prolapse. AB - OBJECTIVE: To compare black and white women with regard to urinary incontinence and prolapse. METHODS: Two hundred consecutive women referred for evaluation of urinary incontinence or severe prolapse, 54 of whom were black, were evaluated. Each had a comprehensive standardized evaluation. Qualitative and quantitative data were analyzed for significant differences between the groups. RESULTS: The symptoms of pure stress, pure urge, and mixed incontinence were described by 7, 56, and 37% of black subjects, respectively, compared to 31, 28, and 41% of white subjects (P = .001). The conditions of pure genuine stress incontinence (GSI), pure motor incontinence, and mixed incontinence were diagnosed in 27, 56, and 17% of black subjects, respectively, compared to 61, 28, and 11% of whites (P = .0008). Black women with mixed symptoms were significantly less likely than white women to have pure GSI (47 versus 74%; P = .05). Blacks with GSI were significantly heavier, had higher parity, more often took a diuretic, were more often diabetic, and had better passive urethral closure pressure but greater urethral axis mobility than whites. Blacks with motor incontinence were significantly younger, heavier, less likely to have had prior continence surgery or hysterectomy, and had better passive urethral closure pressure but smaller bladder capacities than whites. The prevalence of severe prolapse in this referral population was the same for blacks and whites (24 and 23%), although blacks had significantly more vaginal deliveries. No other significant racial differences were noted in the prolapse group. CONCLUSIONS: Black women with urinary incontinence have a different distribution of symptoms, different conditions causing their incontinence, and different risk profiles for these conditions than do whites. The significantly lower prevalence of pure GSI in black women compared to white women makes the clinical evaluation for GSI appreciably less accurate in the individual black patient. Until further epidemiologic information regarding incontinence in black women is available, such women should be considered candidates for more accurate, sophisticated urodynamic testing before continence surgery. PMID- 8437799 TI - Levator ani muscle morphology and recurrent genuine stress incontinence. AB - OBJECTIVE: To assess the impact of levator ani muscle morphology on the outcome of patients with genuine stress incontinence undergoing reconstructive surgery of the pelvic floor. METHODS: A follow-up investigation was performed on 30 patients from a previous study, who had undergone hysterectomy with combined anteroposterior vaginal repair for pelvic floor relaxation and genuine stress incontinence. Biopsy specimens of the pubococcygeal muscle had been obtained during posterior colporrhaphy and subsequently evaluated for evidence of striated muscle tissue. Eleven patients had striated muscle tissue in the biopsy specimens (group A), whereas 19 subjects did not (group B). Before operation and at 41 months (range 37-44) after operation, the patients underwent urodynamics, perineal sonography, and perineometry. RESULTS: At follow-up, all patients in group A were continent, whereas ten of 19 patients (53%) in group B showed recurrent genuine stress incontinence (P < .01). Compared with group B (48.5 +/- 21.9%), group A patients (71.8 +/- 16.5%) had a significantly higher abdominal pressure transmission ratio at follow-up (P = .02). At postoperative perineal sonography, group A patients (107.7 +/- 14.0 degrees) showed a significantly smaller retrovesical angle during straining than did group B patients (134.6 +/- 25.9 degrees) (P < .01). CONCLUSION: The levator ani muscle morphology has prognostic importance for the outcome of patients with genuine stress incontinence undergoing anteroposterior vaginal repair. PMID- 8437800 TI - A comparison of the cough stress test and single-channel cystometry with multichannel urodynamic evaluation in genuine stress incontinence. AB - OBJECTIVE: To assess the predictability and accuracy of a simplified approach- the cough stress test and single-channel cystometry--in the diagnosis of genuine stress incontinence (GSI) by comparing these tests to the more complex multichannel cough urethral pressure profile and urethrocystometry. Conversely, we assessed the predictability and accuracy of the multichannel approach--the cough urethral pressure profile and urethrocystometry--in GSI by comparing these tests to the cough stress test and single-channel cystometry. METHODS: Prospectively, 145 women with complaints of urinary incontinence underwent a complete urogynecologic evaluation. All patients underwent single-channel cystometry with cough stress test and multichannel urethrocystometry with cough urethral pressure profiles in the erect position. Genuine stress incontinence was diagnosed if 1) the patient was seen to spurt urine per urethra with cough at full cystometric capacity in the absence of vesical instability as determined by single-channel cystometry, or 2) the cough urethral pressure profile demonstrated pressure equalization in the absence of vesical instability as determined by multichannel urethrocystometry. Statistical values were calculated for both the simplified and the multichannel methods, and measures of validity were compared statistically. RESULTS: For the diagnosis of GSI, the simplified method had a positive predictive rate of 87.2% and a negative predictive rate of 80.6%. The multichannel method had a positive predictive rate of 84.0% and a negative predictive rate of 84.4%. CONCLUSION: For the diagnosis of GSI, the simplified method of the cough stress test and single-channel cystometry is as accurate and predictive as the multichannel method. PMID- 8437801 TI - Prepubertal ovarian cyst formation: 5 years' experience. AB - OBJECTIVE: To document the frequency of ovarian cyst formation in the prepubertal female and to report on the clinical implications of these cysts. METHODS: We evaluated cases from a retrospective chart review of prepubertal females with ovarian cysts. RESULTS: Over a 5-year period, 1818 ultrasound studies were completed in prepubertal females, from which 99 patients were identified as having ovarian cysts. The majority (82 of 99, 83%) were small, unilocular cysts averaging 2-3 mm in diameter. The incidence of these small cysts ranged at 2-5% in females between birth and age 8. Large ovarian cysts (ie, greater than 2 cm in diameter) are rare in young girls over age 2, with most occurring within the first year of life. Of the 17 large ovarian cysts, two presented with torsion and both were complex on ultrasound examination. Five (29%) of the large ovarian cysts were treated conservatively and demonstrated regression on follow-up; these were unilocular cysts. Although functioning cysts resulting in precocious pseudopuberty are expected to be rare, we identified five cases (5%) in our series. CONCLUSIONS: Small, unilocular ovarian cysts less than 1 cm in diameter are found in prepubertal females with a frequency of 2-5% and are clinically insignificant. Ovarian cysts greater than 2 cm are rare. Unilocular ovarian cysts less than 5 cm may be followed conservatively with ultrasound surveillance until regression, without a major risk of torsion. Ovarian cysts associated with precocious pseudopuberty are generally larger than 2 cm and may be recurrent. PMID- 8437802 TI - Serum levels of placental protein 14 do not accurately reflect histologic maturation of the endometrium. AB - OBJECTIVE: To determine whether serum levels of placental protein 14, a major product of the progesterone-induced secretory endometrium, accurately reflect histologic maturation of the endometrium. METHODS: Daily serum levels of placental protein 14 were compared in 50 normally cycling women with normal or delayed endometrial maturation, as assessed by histologic dating of an endometrial biopsy in the midluteal phase of the same cycle. Ten of these subjects had placental protein 14 measurements but no biopsy in an additional cycle to examine the potential effects of the biopsy on secretion of this protein. RESULTS: Serum placental protein 14 concentrations started to increase 8 days after the LH surge and peaked at similar levels on the first day of the next menses in biopsy and non-biopsy cycles. The biopsy cycles had a shorter luteal phase but a slightly faster increase in placental protein 14 concentrations. Both the integrated secretion of this protein and single measurements on the day of the biopsy or at the onset of the next menses overlapped substantially in women with different degrees of endometrial development, even when differentiation of the endometrium was severely delayed. CONCLUSION: Serum measurements of placental protein 14 do not accurately predict, and thus should not replace, histologic evaluation of the endometrium at nidation. PMID- 8437803 TI - Pregnancy outcome following a second-trimester loss. AB - OBJECTIVE: To evaluate the association between fetal loss in the second trimester and subsequent adverse birth outcomes. METHODS: We identified 95 women in our system who had a pregnancy loss at 13-24 weeks in the years 1985-1990 and tabulated the rates of preterm delivery, stillbirth, and neonatal death in the next pregnancy. We compared these outcomes to two groups: women who delivered at 25-36 weeks in their index pregnancy and those who delivered at term in their index pregnancy. RESULTS: Thirty-nine percent of women who had a pregnancy loss at 13-24 weeks in the index pregnancy had a preterm delivery in their next pregnancy, 5% had a stillbirth, and 6% had a neonatal death, with all outcomes worse than those found in the two control populations. Delivery at 19-22 weeks in the index pregnancy was associated with a 62% preterm delivery rate in the subsequent pregnancy. CONCLUSION: A second-trimester loss, especially one occurring at 19-22 weeks, is associated with a poor prognosis in the subsequent pregnancy. PMID- 8437804 TI - Fetal vibroacoustic stimulation. AB - OBJECTIVE: To review the literature on fetal vibroacoustic stimulation as a method of changing the fetal sleep state during nonstress testing. DATA SOURCES: The MEDLINE data base and reference lists were used to select articles pertaining to human and animal fetal vibroacoustic stimulation. METHODS OF STUDY SELECTION: We reviewed the English-language literature with respect to sound intensity, stimulus duration, and repetition rate as possible means of altering fetal sleep wake cycles. DATA EXTRACTION AND SYNTHESIS: Several criteria have been used to measure fetal response: gestational age, fetal heart rate, fetal movements, fetal breathing movements, fetal habituation, and fetal behavioral states. The use of vibroacoustic stimulation for antepartum and intrapartum fetal assessment and safety issues are also reviewed. CONCLUSION: Although further research is needed, the ability of vibroacoustic stimulation to elicit FHR accelerations has been established, thus decreasing the false-positive rate associated with nonreactive nonstress testing. PMID- 8437805 TI - The Human Genome Project: implications for the practicing obstetrician. AB - The Human Genome Project is an international effort to discern the complete genetic makeup of human beings. The isolation and characterization of genes will offer tremendous opportunities for disease detection, diagnosis, screening, prevention, and counseling. Advances in genetic research are occurring simultaneously with the development of new techniques for prenatal genetic testing. Use of gene therapy in humans likely will lag behind our ability to detect genetic disorders. Consequently, obstetricians will be forced to face some difficult medical, ethical, and social challenges. The possibility of a national cystic fibrosis screening program is an example of the complex problems we will face as new genes are described. The obstetric community needs to participate actively in the debate surrounding the ethical and legal implications of the Human Genome Project. We need to establish clinical standards and use our professional organization to act as a resource for clinicians, the public, and legislatures. Because of the increased requirement for genetic counseling, we recommend an expansion of genetics training for residents and clinicians and the development of computer-based interactive video programs for genetic counseling. PMID- 8437806 TI - A resident teaching program in operative endoscopy. AB - To provide a structured experience in operative endoscopy, a comprehensive teaching program has been incorporated into the obstetrics and gynecology residency program at our institution. This program consists of both a didactic and a hands-on portion. The hands-on session is conducted on a pelvic trainer. This approach to teaching residents operative endoscopy has been widely accepted by residents, faculty, and operating room personnel. PMID- 8437807 TI - Electrical cutting device for laparoscopic removal of tissue from the abdominal cavity. AB - The extraction of large tissue masses from the abdominal cavity during laparoscopic surgery is a time-consuming, complicated process. A new prototype instrument is introduced that allows quick laparoscopic removal of fibromas, ovaries, or other tissues from the abdomen. A cylinder with a coning knife at its intra-abdominal end is placed inside the trocar sleeve and is rotated by an electrical micro-engine attached to the trocar. Cylindrical tissue blocks are cut step by step out of the main specimen and removed from the peritoneal cavity through the sleeve with a grasping forceps. Tissue removed is suitable for histologic examination. The principal application is morcellation of fibromas, whereas use in ovarian disease is limited. This new device provides a safe and effective approach inside the abdominal cavity. PMID- 8437808 TI - Quadruplet pregnancy: contemporary management and outcome. PMID- 8437809 TI - Incidence of breast cancer in a 22-year study of women receiving estrogen progestin replacement therapy. PMID- 8437810 TI - Hemolytic disease of the fetus: a plea for restraint. PMID- 8437811 TI - New York AIDS policies authorized. PMID- 8437812 TI - NIOSH lifting formula changes scope to calculate maximum weight limits. PMID- 8437813 TI - Industry profile: healthcare hazards of the healthcare profession. PMID- 8437814 TI - EPA reports on passive smoke hazards. PMID- 8437815 TI - Paraneoplastic retinopathy syndrome. PMID- 8437816 TI - Keratoconus contact lens failure. PMID- 8437817 TI - Reversal of glaucomatous cupping. PMID- 8437818 TI - Fungal dacryocystitis. PMID- 8437819 TI - The government's cataract guidelines: can science and clinicians find a middle ground? PMID- 8437820 TI - Clinicopathologic study of the effect of radial tears and loop fixation on intraocular lens decentration. AB - PURPOSE: The purpose of this study is to determine the effect of loop fixation and anterior capsular tears on intraocular lens (IOL) decentration. METHODS: A retrospective measurement of IOL decentration was performed on 144 human eyes with posterior chamber (PC) IOLs obtained after death. RESULTS: Decentration in eyes with asymmetrical bag-sulcus fixation (mean +/- standard deviation, 0.64 +/- 0.39 mm) was significantly higher than eyes with symmetrical fixation. In the presence of radial tears, symmetrically fixated IOLs in either the capsular bag or the ciliary sulcus decentered to a similar degree, 0.35 +/- 0.25 mm and 0.4 +/ 0.26 mm, respectively. The least decentration was observed with capsular fixation and no radial tears (0.18 +/- 0.09 mm). This was significantly less decentration than with any other form of fixation in the presence of radial tears. CONCLUSION: This study shows that capsular fixation with no radial tears, as can be achieved by using the continuous curvilinear capsulorhexis, is associated with the least decentration. PMID- 8437821 TI - Scleral flap necrosis and infectious endophthalmitis after cataract surgery with a scleral tunnel incision. AB - BACKGROUND: Long scleral tunnel dissection techniques have been developed for cataract surgery incisions. These incisions reduce postoperative astigmatism and keratorefractive instability. If fashioned correctly, the internal lip of the incision produces a tight seal to the anterior chamber, permissible of sutureless surgery. The behavior of such a wound during intraocular infection is unknown. METHODS: The authors describe two elderly patients in whom postoperative bacterial endophthalmitis was accompanied by infectious scleritis, infectious sclerokeratitis or keratitis, and rapid scleral flap necrosis. One of the patients had a painless disease process. RESULTS: Intraocular isolates of Staphylococcus aureus and Streptococcus equinus were recovered from the two patients, respectively. Management was complicated by loss of tectonic integrity that followed scleral flap necrosis, by impaired vitreoretinal visualization associated with rapidly progressive sclerokeratitis or keratitis, and by bacterial scleritis in the base of the scleral flap. No light perception was retained in either eye. CONCLUSION: Scleral tunnel incisions create a potential abscess cavity. Although a rare occurrence, postoperative endophthalmitis in such an eye may present major surgical and therapeutic problems intrinsic to the wound design. PMID- 8437822 TI - Corticosteroid-induced ocular hypertension in the treatment of aphakic or pseudophakic cystoid macular edema. AB - PURPOSE: To examine the relationship between corticosteroid-induced ocular hypertension and the reduction and/or resolution of chronic aphakic or pseudophakic cystoid macular edema (CME). METHODS: The authors retrospectively reviewed 454 cases coded for CME between 1971 and 1991 and identified 21 patients with aphakic or pseudophakic CME greater than 6 months' duration who experienced a documented rise in intraocular pressure (IOP) on corticosteroid therapy. These patients were compared with similarly treated controls who did not experience a rise in IOP, and visual acuity and the biomicroscopic appearance of CME were examined. RESULTS: Sixteen of 21 patients showed improved visual acuity and reduction and/or resolution of CME. In all five cases of treatment failure, there was evidence of vitreous attachment to anterior segment structures. This is statistically significant compared with controls, in which 4 of 14 patients with normal vitreous anatomy showed similar improvement (P = 0.00003). CONCLUSION: This small retrospective series suggests that in the absence of vitreous traction, corticosteroid-induced ocular hypertension possibly leads to reduction and/or resolution of chronic aphakic or pseudophakic cystoid macular edema. PMID- 8437823 TI - Clinical experience with N-butyl cyanoacrylate (Nexacryl) tissue adhesive. AB - BACKGROUND: To investigate the indications, outcomes, and complications of N butyl cyanoacrylate tissue adhesive for ocular clinical use. This tissue adhesive is under investigation by the Food and Drug Administration. METHODS: N-butyl cyanoacrylate was used as an investigational device on 44 patients at the authors' institution over a 2-year period. The charts of these patients were reviewed. RESULTS: The indications for glue application included corneal perforation (19 eyes), descemetoceles (9 eyes), leaking filtering blebs (6 eyes), stromal thinning (5 eyes), wound leaks (4 eyes), and exposure keratopathy (1 eye). A bandage contact lens was used over the dried tissue adhesive in 38 of the 44 eyes. Length of glue adherence ranged from 1 to 660 days (mean, 72 days). Outcome was penetrating keratoplasty (19 eyes), no further intervention (14 eyes), enucleation (4 eyes), surgical revision of a filter (2 eyes), scleral patch graft (1 eye), conjunctival transplant (1 eye), failed tarsorrhaphy (1 eye), suturing of wound (1 eye), and a lamellar graft (1 eye). Vision improved in 52% (23/44) of eyes. CONCLUSION: This tissue adhesive may soon be available to all ophthalmologists, and the authors' experience demonstrates that it is an effective method of temporary or permanent closure of an impending or frank perforation. PMID- 8437824 TI - Videokeratography of the fellow eye in unilateral keratoconus. AB - PURPOSE: To identify a population of keratoconus patients with unilateral disease based on clinical findings and slit-lamp biomicroscopy and examination with a nine-ring photokeratoscope (Corneascope) and to study the topography of the clinically normal fellow eye with videokeratography. METHODS: Clinical charts and Polaroid Corneascope photographs of both eyes of 200 patients with a diagnosis of keratoconus from three large cornea referral practices in the Los Angeles area were retrospectively reviewed. Patients whose clinical findings were within normal limits and whose Corneascope Polaroid photographs had concentric rings with no detectable abnormalities, consistent with a diagnosis of keratoconus in one eye, were considered unilateral. These patients were recalled to our clinic, and the topography of the apparently normal eye was studied using a Corneascope and a computer-assisted videokeratoscope, the Topographic Modeling System, on the same day. RESULTS: Based on examination with a slit-lamp biomicroscope and the Corneascope, eight patients had unilateral disease. Videokeratography in seven of the eight fellow eyes displayed a pattern of inferior steepening suggesting "early keratoconus." All seven eyes had a positive "I - S value," a quantitative measure, indicating increased dioptric power below the corneal apex. CONCLUSION: Our findings suggest that keratoconus is almost always bilateral. These data support genetic influences in the pathogenesis of this disorder. Additionally, videokeratography data presented might prove useful in the detection of early keratoconus and refining patient selection for myopic keratorefractive procedures. PMID- 8437825 TI - Corneal complications associated with the use of crack cocaine. AB - BACKGROUND: A case series of patients with corneal complications associated with crack cocaine use is presented. Patients had infectious keratitis or sterile epithelial defects. METHODS: Entry criteria into this series included the presence of an infectious corneal ulcer or sterile epithelial defect after the patient used crack cocaine routinely. Patients were prospectively identified from July 1, 1989 to June 30, 1991. RESULTS: Fourteen patients with crack-related corneal problems were identified. In 10 patients with infectious corneal ulcers, both bacterial and fungal organisms were isolated, and patients were treated with appropriate antimicrobial therapy. The group of patients with sterile corneal epithelial defects were seen after they had rubbed their eyes vigorously after crack cocaine use. The epithelial defects were treated and healed without complication. CONCLUSION: Crack cocaine users appear to represent a unique subset of young patients predisposed to infectious keratitis and corneal epithelial defects. A number of hypotheses are offered to explain this effect. Both ophthalmologists and the general public should be aware of these severe corneal problems associated with the use of crack cocaine. PMID- 8437826 TI - Microbial keratitis in childhood. AB - BACKGROUND: Microbial keratitis occurs infrequently in childhood. The leading ocular predisposing factors are trauma and preexisting corneal disease. Many of the age-related risk factors in adults play a minor role in children. METHODS: The authors retrospectively studied 51 eyes with ulcerative keratitis in 50 children younger than 16 years of age. This includes all patients treated at Bascom Palmer Eye Institute during an 11 1/2-year period from January 1, 1980, to June 30, 1991. The criterion for inclusion in the study was a discharge diagnosis of microbial (nonviral) keratitis. RESULTS: The principal risk factors identified in this study were trauma (44%), prior corneal surgery (24%), systemic illness (14%), and contact lens wear (12%). Systemic illness or an immunocompromised state existed in 7 (47%) of the 15 children younger than 3 years of age. There was a large male preponderance (68%). Forty-four (86.3%) of the 51 eyes were culture-positive; six (11.7%) were polymicrobial. Five of seven culture-negative patients had received prior topical antibiotic therapy. Pseudomonas aeruginosa (34%), Staphylococcus aureus (20%), and fungi (18%) were the most common organisms isolated. Seven (14%) eyes required surgery. CONCLUSION: This study presents important differentiating factors between adult and childhood nonviral microbial keratitis. Identification of principal risk factors in children may aid in early recognition and treatment of microbial keratitis. PMID- 8437827 TI - Corneal stromal penetration of topical ciprofloxacin in humans. AB - PURPOSE: Use of fluoroquinolone agents as single drug treatment for severe bacterial keratitis requires that adequate stromal drug concentrations are achievable that exceed the MIC90 for common corneal pathogens. The purpose of this study, therefore, is to document the human stromal penetration of the fluoroquinolone, ciprofloxacin, in human tissue obtained from patients undergoing penetrating keratoplasty. METHODS: Twelve patients, all with intact corneal epithelia, received 0.3% ciprofloxacin (Ciloxan) eyedrops every 15 minutes for the first hour and then every hour for 10 hours before their scheduled keratoplasty. Corneal tissue samples obtained from the excised buttons at the time of surgery were frozen and subsequently analyzed for drug concentration using high-pressure liquid chromatography. RESULTS: A mean corneal tissue concentration of 5.28 +/- 3.4 micrograms/g tissue (mean +/- standard deviation) of ciprofloxacin was determined. Tissue levels ranged from 1.43 micrograms/g of tissue to 10.58 micrograms/g of tissue. CONCLUSION: Ciprofloxacin penetration was variable in patients with an intact epithelium and, in some cases, did not exceed the MIC90 for some gram-positive organisms. The presence of an epithelial defect is expected to potentiate the penetration of ciprofloxacin to most likely exceed the MIC90 for most corneal pathogens. PMID- 8437828 TI - Penetrating ocular injuries secondary to motor vehicle accidents. AB - BACKGROUND: Penetrating ocular trauma is second only to cataracts as the most common cause of visual impairment in the United States; motor vehicle accidents are an important cause of injuries (ocular and non-ocular). METHODS: The files of 293 consecutive patients treated for a penetrating ocular injury over a 5-year period (1986 to 1991) were reviewed, and 10 (3.4%) were associated with a motor vehicle accident. RESULTS: Median age was 27.5 years and median initial visual acuity was 20/200 (range, 20/30 to light perception). A sharp glass fragment penetrating the eye was the mechanism of injury in seven cases. A seatbelt was worn by only one patient. Six patients had a corneoscleral laceration, and two patients each had corneal and scleral lacerations. Primary repair of the laceration was solely performed in eight patients. Vitreous surgery was required in two cases, one with retained intraocular foreign bodies and one with a retinal detachment. The median follow-up period was 5 months, and 8 of 9 retinas remained attached at final follow-up. One patient died of unrelated causes. Final median visual acuity was 20/25 (range, 20/20 to hand motions). CONCLUSION: Among patients in a large series of penetrating ocular injuries, the percentage of injuries due to motor vehicle accidents is low. The anterior segment is predominantly involved, and the final visual prognosis is favorable. Compulsory seatbelt legislation may reduce the frequency and morbidity of these accidents in the United States. PMID- 8437829 TI - Significance, specificity, and ultrastructural localization of HMB-45 antigen in pigmented ocular tumors. AB - PURPOSE: To evaluate the expression of the monoclonal HMB-45 antibody in melanocytic and nonmelanocytic ocular tumors and seek "activated" cellular subpopulations in an attempt to distinguish between benign and malignant melanocytes, to compare HMB-45 and S100 activity, and to determine the specificity of this tumor marker for melanocytic ocular lesions. METHODS: Immunohistologic investigations were performed with paraffin-embedded tissue of 10 acquired conjunctival melanoses, 19 conjunctival nevi, 34 conjunctival melanomas, 69 uveal melanomas, 20 basal cell carcinomas of the lid, 20 cystic dermoids, 15 hemangiomas of the lid, 20 conjunctival papillomas, 20 squamous cell carcinomas, 20 pterygia, 11 sebaceous gland carcinomas, 10 retinoblastomas, and 5 choroidal metastatic carcinomas. The avidin-biotin peroxidase technique and monoclonal HMB-45 antibody were used. The distribution of S100 protein was studied in the melanocytic tumors for comparison. To localize the HMB-45 antigen, lowicryl-embedded tissue of uveal melanomas was investigated immunoelectron microscopically. RESULTS: More than 95% of the conjunctival and choroidal melanomas expressed the HMB-45 antigen, while S100 was found in all melanomas of the conjunctiva and in 91% of the uveal melanomas. In benign melanocytic lesions of the conjunctiva (nevi and melanocytes), especially the intraepithelial and junctional components stained with HMB-45, and at the site of tumor invasion, infiltrating cells showed increased HMB-45 reactivity. On the whole, HMB-45 antigen was less evenly distributed in the melanocytic tumors investigated than S100 antigen. All nonmelanocytic ocular tumors revealed no HMB-45 expression. Retinal pigment epithelium and tumor-free choroid were negative for HMB-45. The HMB-45 antigen was immunoelectron microscopically found in melanosomes at stages II and III. CONCLUSION: HMB-45 immunohistology helps in distinguishing melanocytic from nonmelanocytic ocular tumors and often clarifies the front of tumor invasion. The stronger HMB-45 reactivity probably reflects melanocytic activation, but a sharp line between benign and malignant melanocytes cannot be drawn. PMID- 8437830 TI - Plaque radiotherapy in the management of retinoblastoma. Use as a primary and secondary treatment. AB - BACKGROUND: Radioactive episcleral plaque brachytherapy is a treatment method for selected retinoblastomas. The authors have used this technique since 1976 as both a primary and a secondary treatment method after other methods failed to achieve tumor control. METHODS: A review of the records of 400 consecutive children with retinoblastoma showed that solitary plaque radiotherapy was used as a method of management in 103 cases. The authors' overall experience was evaluated, and the results between primary and secondary plaque therapies were compared in these 103 cases. RESULTS: Of the 103 tumors, the mean basal diameter was 7 mm, and the mean thickness was 4 mm. Overlying vitreous seeds were clinically apparent in 50 cases (48%). The mean proximity of the tumor margin to the optic disc margin was 6 mm and to the foveola was 6 mm. The mean follow-up period was 40 months. In 89 cases (86%), the tumor was controlled by one plaque application, whereas in 13 cases (13%), tumor recurrence after initial tumor shrinkage necessitated subsequent treatment. Final visual outcome was good in 63 cases (62%), poor in 30 (29%), enucleation in 9 (9%), and unknown in 1 case. The poor vision was due to foveal retinoblastoma (with or without amblyopia) in 25 cases (83%). Eight of the nine enucleated eyes were treated initially with external beam radiotherapy then later with plaque radiotherapy. In 31 cases (30%), plaque radiotherapy was used as a primary treatment to the tumor, while in 72 cases (70%), it was a secondary form of management after failure of other methods to control the tumor. Statistical analysis showed that tumors treated with plaque radiotherapy as a primary measure were more likely to be larger in in base (P = 0.01) and thickness (P = 0.01) than secondary treated tumors. The secondary treated retinoblastomas were more likely to have vitreous seeds (P = 0.02) than the primary treated tumors. The rate of tumor control and patient survival was similar between the two groups. CONCLUSION: Plaque radiotherapy is very effective in treating selected retinoblastomas with a high rate of tumor control and patient survival. It can be used successfully as a primary or a secondary treatment for tumors that have not been adequately controlled by other therapeutic methods. PMID- 8437831 TI - Clinical manifestations of posterior precortical vitreous pocket in proliferative diabetic retinopathy. AB - BACKGROUND: In diabetic retinopathy, fibrovascular tissue is prone to form around the macular area in a circular pattern. Posterior precortical vitreous pocket is a physiologically presented premacular liquefied lacuna of the vitreous. The authors studied how a posterior precortical vitreous pocket affects the clinical feature of proliferative diabetic retinopathy (PDR). METHODS: The authors examined the vitreous of 148 diabetic eyes from 114 patients with a ring- or C shaped fibrovascular tissue surrounding the posterior fundus. RESULTS: A cone shaped partial posterior vitreous detachment was a common feature of the vitreous. A posterior vitreous detachment was prevalent outer to the ring-shaped proliferation. In the posterior fundus inner to the ring, only the gel component of the vitreous was detached from the fundus with the cortical vitreous still attached onto the retina. The premacular liquefied lacuna was identified as the posterior precortical vitreous pocket. The profile of this pocket became obvious when vitreous hemorrhage settled within the posterior precortical vitreous pocket. The ring-shaped proliferation was formed along its the outer margin. CONCLUSION: These results suggest that a posterior precortical vitreous pocket plays a key role in determining the pattern of proliferation in some types of diabetic retinopathy. PMID- 8437832 TI - Prognostic factors in the natural course of retinopathy of prematurity. The Cryotherapy for Retinopathy of Prematurity Cooperative Group. AB - BACKGROUND: There exists no reliable information that allows the ophthalmologist to predict with any degree of certainty a particular infant's chances of requiring surgical treatment for retinopathy of prematurity (ROP) or of reaching an unfavorable outcome on the basis of the retinal findings at the time of the nursery examination. METHODS: In the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP), 4099 infants weighing less than 1251 g at birth underwent eye examinations that began at 4 to 6 weeks after birth and subsequently continued at 2-week intervals. Independent variables in the population were studied using multiple logistic regressions. RESULTS: An increased risk of reaching threshold ROP was found associated with lower birth weights, younger gestational age, white race, multiple birth, and being born outside a study center nursery. For infants who developed ROP (66%), corresponding probabilities are presented for developing severe ("threshold") ROP or of having an unfavorable macular outcome. The risk of an unfavorable macular outcome was increased with zone 1 ROP, "plus" disease, the severity of the stage, and the amount of circumferential involvement. A higher risk also was associated with a rapid rate of progression of ROP to prethreshold disease but not with the postconceptional age at which ROP was first noted. CONCLUSION: The findings indicate that the ocular characteristics of ROP, along with some easily identifiable and available basic systemic and demographic information about an infant, can assist the ophthalmologist in understanding variations in an individual baby's chance for a good or poor macular outcome. PMID- 8437833 TI - Diode laser photocoagulation for threshold retinopathy of prematurity. A randomized study. AB - BACKGROUND: Although peripheral cryotherapy decreases the incidence of unfavorable anatomic outcomes in threshold retinopathy of prematurity (ROP), apnea, bradycardia, and lid edema can occur. Argon laser indirect ophthalmoscope photocoagulation has been used as an alternative to cryotherapy, with fewer adverse effects. Retinal lesions placed with diode lasers are deeper than similar argon laser lesions, and it is not known whether this difference could influence the response to ablative therapy. METHODS: Patients were enrolled under a prospective, randomized protocol. One eye of each patient with symmetric, threshold ROP was treated with an 814/815 nm diode laser, while the other eye was treated with cryotherapy. Patients with asymmetric diseases also were randomized for treatment in the threshold eye. RESULTS: Nineteen infants (33 eyes) were treated, ranging from 485 to 863 g birth weight (23 to 27 weeks gestational age); 18 patients (32 eyes) were followed for 3 months or longer. Four patients (8 eyes) had bilateral zone 1 disease. Postconceptional age was 36 to 45 weeks at the time of treatment. The diode laser treatment was better tolerated than cryotherapy, and the treatment apparatus was more easily transported. Apneic episodes requiring intubation resulted from two cryotherapy sessions but no diode laser sessions. Five cryotherapy-treated eyes required retreatment because of persistent disease with adjacent skip areas. In the group followed for 3 to 15 months, 1 cryotherapy-treated eye and 1 diode laser-treated eye progressed to stage 5 retinal detachment. CONCLUSION: Compared with cryotherapy, the diode laser was more convenient, technically easier to administer, and better tolerated by the patient. Although the number of patients was too small for meaningful statistical analysis of outcome, diode laser peripheral retinal ablation appeared to be as effective as cryotherapy for the treatment of threshold ROP. PMID- 8437834 TI - Anterior transposition of the inferior oblique muscle for dissociated vertical deviation. AB - BACKGROUND: Recently, anterior transposition of the inferior oblique muscle was reported to be an effective treatment for dissociated vertical deviation (DVD), but data on long-term stability have not been reported. METHODS: A retrospective, longitudinal analysis of 17 consecutive patients (22 eyes) with dissociated vertical deviation and inferior oblique overaction who had an anterior transposition of the inferior oblique for significant dissociated vertical deviation and a minimum of 12 months postoperative follow-up was undertaken. The size and degree of control of the dissociated vertical deviation and the degree of inferior oblique overaction were assessed preoperatively, and postoperatively at 1 week, at 4 to 6 months, and when last seen. The frequency of postoperative hypotropia and elevation deficits were noted. RESULTS: The mean preoperative dissociated vertical deviation measured 13.4 delta, and the mean total vertical deviation measured 16.2 delta in primary position at 6 meters. The mean dissociated vertical deviation at last follow-up measured 6.7 delta, and the mean total vertical deviation was 7 delta. The dissociated vertical deviation remained controlled based on objective evaluation and subjective patient/relative response in 19 of 22 eyes after a mean follow-up of 2 years (range, 1 to 4.9 years). It recurred in one eye by 6 months postoperatively and in 3 eyes at the last examination. The inferior oblique overaction did not recur to a significant extent in any patient. The best results were achieved in eyes with preoperative dissociated vertical deviations less than 15 delta (0 of 11 failures). When the preoperative dissociated vertical deviation measured > 15 delta, 3 of 11 were failures. Postoperative primary position hypotropia was uncommon (1 of 17 patients), whereas 27% of eyes had mild postoperative elevation deficits in abduction and adduction. CONCLUSION: Anterior transposition of the inferior oblique is an effective treatment for dissociated vertical deviation with inferior oblique overaction but may be less stable in the long term when the preoperative dissociated vertical deviation is in excess of 15 delta. PMID- 8437835 TI - Ptosis repair by single suture aponeurotic tuck. Surgical technique and long-term results. AB - PURPOSE: To assess the effectiveness and long-term results of a simplified aponeurotic tuck technique for ptosis repair. METHODS: The author simplified the aponeurotic approach for ptosis repair by minimizing the dissection and using a single 6-0 nylon stitch to control the lid height and curvature. Prospectively, 169 ptotic lids were repaired by this technique over a 7-year period. All consecutive patients with ptosis ranging from 1 to 5 mm, levator function greater than 8 mm, and with no history of previous eyelid surgery were included. Patients with measurements and levator function outside of this range or who had ptosis secondary to eyelid or orbital mass, as a complication of eyelid surgery, or associated with systemic disease were excluded. The follow-up period ranged from 18 to 96 months, with an average of 60 months. RESULTS: Of the 169 eyelids, 162 (95%) were corrected to 1 mm. There were 12 reoperations, including 4 on patients who had initial correction to within 1 mm. Complications included overcorrection in three patients and undercorrection in six, peaking in five, and two immediate recurrences and three late recurrences. Long-term results were excellent, as no change in the lid height was observed. CONCLUSION: The single-stitch aponeurotic tuck is simple, effective, and versatile. It can be used in the correction of involutional, postcataract, traumatic, and congenital types of ptosis. Although local anesthesia is preferred, consistent results also can be obtained in those cases where general anesthesia is indicated. The complications that occurred were minimal and easily corrected. PMID- 8437836 TI - Controlled tissue expansion in periocular reconstructive surgery. AB - BACKGROUND: Soft tissue expansion is a technique useful in reconstruction when a shortage of tissue exists. This method allows the creation of skin similar in appearance and type to that immediately adjacent to the defect. The use of this technique as a stage in repairing large periocular defects is presented. The sequence of implant placement, expansion, and ensuing eyelid reconstruction is illustrated. METHODS: The soft tissue adjacent to an eyelid defect was expanded by means of a subcutaneously implanted reservoir that was progressively inflated over several weeks by percutaneous injection of fluid. The prosthesis was removed after adequate expansion had been achieved. The expanded tissue was then used to fashion a local flap to resurface the defect. RESULTS: Upper eyelid skin expansion was performed in one patient, and five patients received expansion in an adjacent area. The expanded tissue was then used to reconstruct the eyelid defect. The only complications encountered were tissue necrosis at the tip of an advancement flap in one patient and hematoma formation within the dissection pocket after expander insertion in another patient. CONCLUSIONS: This technique complements existing reconstructive methods and provides a valuable surgical alternative for managing various periocular defects. The potential application of this technique in eyelid and periocular reconstruction appears promising. PMID- 8437837 TI - A prospective three-year study of response properties of normal subjects and patients during automated perimetry. AB - PURPOSE: The purpose of this study is to evaluate prospectively the reliability characteristics of patients undergoing automated perimetry over a 3-year period and compare these results with the results of previous investigations. METHODS: The subjects included 48 normal observers, 32 ocular hypertensive subjects, and 19 patients with early glaucomatous visual field loss. Both eyes were tested annually for 3 years with automated perimetry, using the standard procedures for the Humphrey Field Analyzer. Fixation losses, false-positive errors, false negative errors, and short-term variability (double determinations) were evaluated. RESULTS: Short-term variability was slightly higher for the early glaucoma group than for the normal observer and ocular hypertensive groups, but there were no meaningful changes in short-term variability over 3 years. False positive errors were very low in all three groups throughout the investigation. False-negative errors were slightly higher in the early glaucoma group, but all three groups had relatively low false-negative error rates throughout the study. Fixation losses were the most common source of unreliable results. The number of fixation losses decreased for the second and third years of the study. CONCLUSION: Contrary to a previous report, a relatively low number of unreliable tests were found for both initial and follow-up visits. The majority of unreliable visual field tests were sporadic events. Only a few subjects repeatedly produced unreliable test results. The authors conclude that automated perimetry can provide a reliable means of following patients over extended periods of time. PMID- 8437838 TI - Influence of pupil size, anisocoria, and ambient light on pilocarpine miosis. Implications for supersensitivity testing. AB - BACKGROUND: This study determines how pupil size, anisocoria, and ambient light influence miotic responses to dilute pilocarpine. The aim is to establish whether mechanical properties of the iris affect miotic behavior using a cholinergic agonist and, if so, to define a more specific clinical definition of supersensitivity testing for suspected tonic pupil disorders. METHODS: The right pupil of 42 normal subjects was first dilated with phenylephrine to create an experimental anisocoria. Then, pilocarpine 0.1% was placed in both eyes. Net constriction of the larger right pupil was determined by subtracting the amount of pilocarpine-induced constriction of the control left pupil from the amount of pilocarpine-induced constriction of the experimental right pupil. Pupil diameters were measured in room light and darkness. RESULTS: In only a few subjects, the larger right pupil became smaller than the left pupil after pilocarpine administration. Net constriction of the right pupil was greater when determined in room light than in darkness. The amount of net constriction of the right pupil showed good correlation with the degree of baseline anisocoria when evaluated in room light, but not so in darkness. CONCLUSION: Pupil size, degree of anisocoria, and light conditions influence the amount of pilocarpine-induced change in anisocoria. If a patient's larger pupil becomes the smaller pupil in darkness after dilute pilocarpine is applied to both eyes, then it is likely that such a response occurred independent of mechanical properties of the iris, and likely represents a supersensitive response. Ophthalmology. PMID- 8437839 TI - Alternating skew on lateral gaze. Neuroanatomic pathway and relationship to superior oblique overaction. AB - BACKGROUND: Previous studies of patients with heterogeneous, often diffuse neurologic disorders concluded that the neurologic substrate for alternating skew on lateral gaze may be localized at the level of the brain stem tegmentum or the cervico-medullary junction, or both. The localized nature of brain tumors offers an opportunity to further investigate the anatomic localization for this as well as other conditions. METHODS: To test the hypothesis that cervico-medullary and cerebellar lesions are responsible for alternating skew on lateral gaze, the authors investigated a series of 50 children with brain tumors, 39 of whom showed neuro-ophthalmologic abnormalities on clinical testing. Seven children had alternating skew on lateral gaze. RESULTS: All seven children with alternating skew on lateral gaze showed neoplastic involvement at the level of the cervico medullary junction and/or the cerebellum on critical analysis of neuro-imaging studies. CONCLUSION: The authors conclude that the neuroanatomic substrate for alternating skew on lateral gaze is localized at the level of the cervico medullary junction and/or the cerebellum. Knowing that (1) alternating skew on lateral gaze closely mimics superior oblique overaction clinically, (2) superior oblique overaction is frequently found in patients with myelomeningocele, and (3) myelomeningocele is uniformly associated with Arnold-Chiari type II which includes cerebellar and cervico-medullary region abnormalities, the authors propose that alternating skew on lateral gaze and superior oblique overaction associated with myelomeningocele have similar neuroanatomic pathways. PMID- 8437840 TI - Alanine mutagenesis of conserved residues in the platelet-derived growth factor family: identification of residues necessary for dimerization and transformation. AB - Platelet-derived growth factor (PDGF) and vascular endothelial growth factor define a family of dimeric proteins characterized by eight conserved cysteine residues involved in disulfide bonds. Thirteen non-cysteine residues conserved among the platelet-derived/vascular endothelial growth factors were individually mutated to alanine in v-sis/PDGF-B. In addition, five other residues flanking F148 were also mutated to alanine. The resulting mutants were assayed for transformation of NIH3T3 cells, and the mutant proteins were assayed for their ability to dimerize. Four residues were found to be crucial for disulfide-linked dimer formation: P152 and G162 were mandatory, while R159 and H205 also contributed to efficient dimerization. Four of the mutant proteins (at residues N147, F148, L149 and K185) dimerized efficiently yet exhibited less than 50% transforming activity compared with wild-type v-sis. Two mutants (at residues D142 and F148) were located in a region important for PDGF receptor interaction and were further studied with regard to secretion and PDGF receptor autophosphorylation. A series of substitutions at residue F148 revealed a strong preference for aromatic amino acids. One mutant from this series (F148G) dimerized but was completely inactive for transformation. This study thus identifies four residues in v-sis/PDGF-B important for dimerization and also identifies additional residues critical for full activation of PDGF receptors. The E5 oncoprotein encoded by bovine papillomavirus type I exhibits two short regions of amino acid similarity when compared with the minimal transforming region of v-sis/PDGF-B. Several of the v-sis mutants discussed in this work affect residues that are also present in the E5 oncoprotein, including F148, L149 and H205. PMID- 8437841 TI - Serum factors and v-src control two complementary mitogenic pathways in quail neuroretinal cells in culture. AB - Quail neuroretinal cells (QNR cells) from 7-day-old embryos do not proliferate even in the presence of 8% fetal calf serum. After infection by the Rous sarcoma virus (RSV) they proliferate actively and exhibit a transformed phenotype; this effect is mediated by the oncoprotein pp60v-src. Secondary cultures infected by the thermosensitive strain tsNY68 of RSV are blocked in G0 either by thermal inactivation of pp60v-src at 41.5 degrees C or by serum deprivation at the permissive temperature (36.5 degrees C). Cell division is reinduced either by pp60v-src thermal renaturation or by subsequent serum addition. Our results indicate that v-src and serum control two synergic pathways leading to G0/G1 transition in QNR cells. In order to characterize genes related to the mitogenic and transforming effects of v-src in nerve cells, we have constructed a cDNA library from QNR cells transformed by tsNY68. We report the properties of five molecular clones isolated by differential screening of this library. Unlike immediate-early genes like c-fos, they are induced in mid and late G1. Four of them correspond to unknown mRNAs and the last one codes for nucleolin. This set of v-src-regulated genes is likely to code for functions deficient in terminally differentiated QNR cells and necessary for the progression in G1. PMID- 8437842 TI - p53 gene mutations in human epithelial skin cancers. AB - In the present study we analysed 38 epithelial skin cancers, 19 basal cell carcinomas (BCCs), 13 squamous cell carcinomas (SCCs) and six Bowen diseases (BwDs), using a combination of polymerase chain reaction (PCR) and single stranded conformation polymorphism (SSCP) techniques for the presence of p53 and RAS gene mutations. Whereas 48% (9/19) of the BCCs tested presented a mutated p53 gene, the frequency was lower (15%, 2/13) in our series of SCCs and negative in the BwDs. Nine of the 11 characterized mutations were single-nucleotide substitutions and, interestingly, seven of these involved CC dimers, where a C was changed into a T or a G (three C-->T transitions and four C-->G transversions). This mutational pattern, added to the fact that all the mutated tumors occurred at sun-exposed body sites, implicates UV light in their genesis. Furthermore, we observed two internal deletions of 6 and 24 bp whose flanking sequences contained two or three Cs on either strand. In addition to molecular detection, we searched for p53 protein accumulation, by immunocytochemical staining, in a subset of 23 epithelial skin tumors (nine bearing a mutation, 14 which scored negative in our assay). Three commercially available anti-p53 antibodies (PAb CM1, mAbs DO7 and 1801) were used, and 3/23 (all showing a mutated p53 gene) presented specific nuclear staining. In contrast to other reported data we could not detect any activating RAS gene mutation in our series of human skin cancers. PMID- 8437843 TI - An immediate early human gene encodes an Id-like helix-loop-helix protein and is regulated by protein kinase C activation in diverse cell types. AB - Transcription factors characterized by the presence of a helix-loop-helix (HLH) domain play a central role in the regulation of cell growth/differentiation and tumorigenesis. We report here the cDNA sequence of a human early-response gene, designated HLH 1R21, encoding a 15-kDa HLH protein that lacks a basic, DNA binding domain and which by a number of criteria appears to be the human homologue of mouse HLH 462. Like its murine counterpart, HLH 1R21 protein functions as an Id (inhibitor of DNA binding) transcription factor by inhibiting the binding of E2A-containing protein complexes to muscle creatine kinase E-box enhancer oligonucleotide in vitro. However HLH 1R21 does not inhibit the binding of HLH Max protein to a Max-binding oligonucleotide in vitro, indicating that it has limited promiscuity in its ability to antagonize the function of other HLH transcription factors. In addition, HLH 1R21 mRNA transcripts are regulated by phorbol ester treatment of a diverse range of human cell lines and, when overexpressed in mouse NIH3T3 cells, HLH 1R21 induces a morphologically transformed phenotype. PMID- 8437844 TI - T1, an immunoglobulin superfamily member, is expressed in H-ras-dependent epithelial tumours of mammary cells. AB - T1 is a glycosylated protein in the carcinoembryonic antigen (CEA) family of tumour marker molecules. It was originally identified by virtue of its transient induction after the expression of p21H-ras in NIH3T3 fibroblasts. Here we show that the T1 gene is activated in mammary adenocarcinomas of transgenic mice harbouring an H-ras transgene under the control of the mammary-specific whey acidic protein (WAP) promoter. By contrast, T1 mRNA was not, or only faintly, detectable in mammary carcinomas of transgenic mice bearing a WAP-myc transgene. Thus, T1 overexpression does not appear to be a general tumour-specific phenomenon. A dependence of T1 gene expression on the action of p21H-ras is suggested by the observation of T1 mRNA in nude mouse tumours generated from H ras-transformed cultured mammary epithelial cells. Interestingly, activation of the T1 gene is also found during the maturation of the mammary gland (3-4 weeks after birth), whereas it is absent during its terminal differentiation in pregnancy and lactation. This expression pattern suggests a role for the secreted T1 glycoprotein in the phase of epithelial proliferation of the mammary gland. It appears that p21H-ras-induced transformation of mammary epithelial cells mimics the situation occurring in puberty. In both developmental stages the T1 glycoprotein might affect cell interactions of the proliferating epithelial cells with the surrounding stroma. It might thus promote ductal outgrowth in gland maturation as well as invasive growth of p21H-ras-transformed mammary epithelial cells. PMID- 8437845 TI - The 12S adenoviral E1A protein immortalizes avian cells and interacts with the avian RB product. AB - Quail cells were immortalized for the first time by using retroviruses expressing the 12S adenoviral E1A gene. In these cells, interaction between the 12S E1A product and the quail RB protein was shown, suggesting that the 12S adenoviral E1A product works in avian cells through similar biochemical pathways as in mammalian cells by interacting and inactivating host cellular proteins, including the RB product. These results confirm that the RB product exhibits a universal function among higher vertebrates in controlling cellular growth and tumor progression. PMID- 8437846 TI - E1A oncogene expression level in sarcoma cells: an independent determinant of cytolytic susceptibility and tumor rejection. AB - Ad2/5 E1A oncogene expression induces cytolytic susceptibility of rodent cells to natural killer lymphocytes. To determine whether the requisite thresholds of E1A oncoprotein expression differ for induction of cytolytic susceptibility as compared with other E1A-related activities, sarcoma cells expressing low or normal levels of E1A oncoproteins were compared for differences in morphological transformation, transactivation of viral genes, cytolytic susceptibility and tumorigenicity. Low-level E1A expression transformed sarcoma cells and transactivated the Ad5 E2A gene but did not induce the increased cytolytic susceptibility observed with normal levels of E1A expression. Furthermore, low level E1A expressers retained the tumorigenicity of parental cells, whereas normal-level expressers were non-tumorigenic in hosts with intact natural killer (NK)-cell responses. In contrast to E1A, E1B oncogene expression caused no changes in morphological, cytolytic or tumorigenic phenotypes in these sarcoma cells. These data define an expression threshold for E1A-induced cytolytic susceptibility and associated NK-cell-dependent tumor rejection. The results suggest that the cellular mechanisms involved in E1A induction of cytolytic susceptibility differ from those involved in E1A-mediated cellular transformation and viral gene transactivation. PMID- 8437847 TI - Differences in the interaction of p21c-Ha-ras-GMP-PNP with full-length neurofibromin and GTPase-activating protein. AB - Neurofibromin, the product of the neurofibromatosis type 1 gene, was found to form a stable complex with immobilized p21c-Ha-ras-GMP-PNP (a non-hydrolyzable GTP analog). This complex, detectable as early as 30 min after addition of crude brain extract, is extremely stable, with less than 50% dissociating after 5 h at 4 degrees C. We interpret this to suggest that the dissociation of full-length neurofibromin from p21c-Ha-ras-GMP-PNP is tightly linked to the hydrolysis of GTP to GDP. Failure to remove a significant proportion of the bound neurofibromin in the presence of EDTA and GDP implies that the binding of neurofibromin to p21c-Ha ras-GMP-PNP results in the ras protein becoming resistant to guanine nucleotide exchange. Under conditions in which neurofibromin quantitatively binds to p21c-Ha ras-GMP-PNP, we were unable to detect a complex between p21c-Ha-ras and GAP (GTPase-activating protein). The failure to detect GAP binding to immobilized p21c-Ha-ras-GMP-PNP cannot be explained by the known differences in affinities of the GAP-related domain of neurofibromin and GAP for p21c-Ha-ras-GTP. GAP is, however, able to interact biochemically with immobilized p21c-Ha-ras, suggesting a difference in the interaction between GAP and neurofibromin with p21c-Ha-ras GMP-PNP. PMID- 8437848 TI - Regulation of Xenopus c-myc promoter activity in oocytes and embryos. AB - We have studied the regulation of transcription of the Xenopus c-myc I gene in oocytes and embryos. Various 5' and internal deletions of a 1310-bp-long c-myc I promoter fragment have been ligated upstream of the chloramphenicol acetyl transferase (CAT) reporter gene and microinjected into oocytes and fertilized eggs. Activity was determined by CAT assay and primer extension. The c-myc promoter drives transcription very efficiently, and a truncated promoter -158/+46 essentially retains full activity. This region contains an overlapping E2F/SP1 site and two tandem Sp1 sites homologous to those found in the c-myc gene of mouse. Internal deletions show that both elements are equally active in oocytes in driving the expression of CAT. A germinal vesicle extract contains a DNA binding activity specific for an Sp1 consensus sequence but not the E2F site. The data suggest that the high transcription level of the endogenous c-myc gene in Xenopus oocytes is mediated by Sp1 or a related transcription factor. In embryos a different mechanism emerges and the functional role of the Sp1 binding sites appears to be less important. PMID- 8437849 TI - Different structural organization of Ras and Rho effector domains. AB - Ras regulates proliferation and differentiation signals in cells, and activation of the protein can lead to malignant transformation. Activation of the related protein, Rho, affects cell morphology, and it has been suggested that it may also have some oncogenic potential. We show here that Rho does not induce a malignant phenotype in NIH3T3 cells but instead is a potent activator of actin stress fibre formation. The limited homology between Ras and Rho has enabled us to determine the amino acids specifying their different biological activities and GTPase activating protein (GAP) protein sensitivities using chimeras. Rho substituted with amino acids 23-46 of Ras induces transformed foci in NIH3T3 monolayers, and we conclude that Ras has a single effector domain required for downstream signalling. Although mutational analysis of Rho has revealed that residues 32-42 are also essential for its biological activity, Ras substituted with amino acids 25-48 of Rho does not induce actin stress fibre formation. On the basis of these experiments, we propose that Rho may have two effector domains: one at amino acids 32-42 and corresponding to the effector region of Ras and the second located elsewhere in the carboxy-terminal two-thirds of the molecule. PMID- 8437850 TI - Frequent loss of heterozygosity on chromosome 14 occurs in advanced colorectal carcinomas. AB - The current model for colorectal tumorigenesis defines four specific mutations (activation of a ras proto-oncogene and inactivation of the APC, p53 and DCC tumor-suppressor genes) that accumulate in a colonic epithelial cell as it progresses towards a carcinoma. However, further mutations must be needed for progression to malignancy because advanced adenomas have been observed with all four of these mutations. Loss of heterozygosity (LOH) for 11 loci spanning the distal portion of the long arm of chromosome 14 was studied in 89 sporadic colorectal adenocarcinomas and 25 adenomas. The overall rate of LOH in carcinomas was 53% (46/86 informative carcinomas). The smallest region of overlap (SRO) of deletions includes the markers D14S19 to D14S20. No LOH was seen in the 18 informative adenomas examined. There was a significant trend towards higher levels of LOH within the SRO in advanced Dukes' stages (P = 0.016). Since frequent loss of heterozygosity in a specific region of a chromosome may reflect the inactivation of a tumor-suppressor gene located there, these data suggest that a gene involved in the progression of colonic neoplasia may reside on the distal portion of the long arm of chromosome 14, and that its inactivation may be a critical event in this process. PMID- 8437851 TI - Products of the TAL1 oncogene: basic helix-loop-helix proteins phosphorylated at serine residues. AB - TAL1 gene rearrangement is observed in nearly 30% of patients with T-cell acute lymphoblastic leukemia (T-ALL), and thus it represents the most common genetic lesion associated with this disease. Nevertheless, the presence of TAL1 gene products in normal or leukemic cells has not been reported. Therefore, immunoprecipitation with anti-TAL1 antisera was used to demonstrate the presence of TAL1 phosphoproteins, pp42TAL1 and pp22TAL1, in both T-ALL and erythroleukemia cell lines. The pp42TAL1 and pp22TAL1 proteins appear to be phosphorylated forms of full-length and truncated TAL1 gene products respectively. Phosphoamino acid analysis revealed that pp42TAL1 contains phosphoserine residues. The TAL1 phosphoproteins were detected in all of the T-ALL cell lines that harbor obvious TAL1 gene rearrangements. Interestingly, pp42TAL1 and pp22TAL1 were also present in some, but not all, of the T-ALL lines without detectable TAL1 gene alterations. Therefore, TAL1 activation may promote leukemogenesis in a far greater proportion of T-ALL patients than the 30% that bear gross TAL1 gene rearrangements. PMID- 8437852 TI - Escape from redox regulation enhances the transforming activity of Fos. AB - Fos and Jun form dimeric complexes that bind to DNA sequences containing activator protein 1 (AP-1) sites and regulate gene expression. The in vitro DNA binding activity of these proteins is sensitive to reduction-oxidation (redox). Reduction of a single conserved cysteine residue, located in the DNA-binding domain, either by reducing agents or by a nuclear redox factor (Ref-1), is required for AP-1 DNA-binding activity. Replacing the critical cysteine with serine results in a protein that can bind to DNA in vitro even under oxidizing conditions. To determine whether redox control affects the function of Fos in vivo, we have constructed, and compared the properties of, retroviral vectors expressing either a truncated Fos protein (F118-211) or a truncated Fos protein in which the critical cysteine was replaced by serine (FC154S). In infected chicken embryo fibroblasts (CEFs), both vectors expressed similar levels of Fos protein, which formed heterodimers with Jun at equivalent efficiencies. However, extracts from cells expressing FC154S exhibited a threefold increase in AP-1 DNA binding activity compared with cells expressing F118-211. Furthermore, this enhanced binding activity was resistant to treatment with the oxidizing agent diamide. Infection of CEFs by virus expressing FC154S resulted in increased numbers of transformed colonies and an increase in colony size compared with those obtained following infection by virus expressing Fos 118-211. These results suggest that redox regulation may limit the total level of functional Fos-Jun complexes in vivo and that escape from this control enhances transforming activity. PMID- 8437853 TI - Phosphorylation of serum response factor by casein kinase II: evidence against a role in growth factor regulation of fos expression. AB - Serum response factor (SRF) is a transcription factor involved in the serum and growth factor regulation of the c-fos gene. SRF is phosphorylated by casein kinase II (CKII), which causes a large increase in its DNA-binding activity. CKII activity has been shown to be stimulated by growth factors and serum. Since c-fos transcription is induced by a number of the same agents that stimulate CKII activity, and since fos activation and CKII stimulation demonstrate similar rapid kinetics, a role was proposed for CKII in regulating fos expression via its phosphorylation of SRF. In this report, we provide evidence against this hypothesis by using several different strategies. First, by immunoprecipitation of SRF from cells, we show that the phosphorylation state of SRF does not change upon growth factor treatment. Second, by two-dimensional electrophoresis of lysates from a cell line that overexpresses SRF, we show that, although SRF exists in the cell in several different isoforms, there is no change in their relative amounts upon serum stimulation. Third, we tested the activity of an SRF mutant that binds DNA at constitutively high levels irrespective of CKII phosphorylation. If phosphorylation is regulatory, this mutant would be expected to constitutively activate (or repress) fos expression. However, when overexpressed stably in cells this mutant had no effect on endogenous c-fos expression, suggesting that CKII phosphorylation of SRF is not the limiting event for fos activation. PMID- 8437854 TI - Molecular cloning and analysis of cDNA encoding the murine c-yes tyrosine protein kinase. AB - The cellular yes (c-yes) gene is a member of the class of proto-oncogenes that encode non-receptor tyrosine protein kinases. In this report we describe the isolation of cDNAs that encode the murine c-yes gene product and analysis of the nucleotide sequence of the murine c-yes cDNA clones. The reading frame encodes a protein of 541 amino acids with a calculated molecular mass of 60.63 kDa that is reactive with anti-Yes antisera and possesses protein kinase activity. PMID- 8437855 TI - v-Rel and c-Rel are differentially affected by mutations at a consensus protein kinase recognition sequence. AB - The avian retroviral oncoprotein v-Rel and its cellular homolog c-Rel are members of a family of related site-specific DNA-binding proteins. Towards the carboxy terminal end of the highly conserved Rel homology (RH) domain in the majority of Rel proteins, there is a consensus recognition sequence for protein kinase A (PK A). We have investigated the importance of this sequence (Arg-Arg-Pro-Ser) for several functional properties of v-Rel and c-Rel. Disruption of the PK-A sequence by a two amino acid insertion between the arginine and the proline residues completely abolished the ability of v-Rel and c-Rel to bind a kappa B site in vitro. When the phosphorylatable serine in this sequence (Ser-275 in v-Rel, Ser 266 in c-Rel) was replaced by an alanine, DNA binding by v-Rel was not affected, whereas the ability of c-Rel to bind DNA was reduced approximately fourfold by this mutation. Similarly, a serine to tryptophan change greatly reduced the DNA binding ability of c-Rel, whereas v-Rel was not appreciably affected by this change. When this serine was replaced by an acidic amino acid, DNA binding by v Rel was reduced approximately twofold and the DNA-binding activity of c-Rel was nearly abolished. Glutaraldehyde cross-linking experiments indicated that mutations at the PK-A recognition site that reduced DNA binding also negatively affected protein oligomerization, which is likely to be responsible for the reduced ability of mutant v-Rel and c-Rel proteins to bind DNA. Domain-swapping experiments showed that structural differences between v-Rel and c-Rel in the central region of the proteins are primarily responsible for the higher sensitivity of c-Rel to a serine to alanine mutation in the PK-A site. One difference between v-Rel and c-Rel, a glutamine to alanine change in v-Rel located three amino acids carboxy-terminal to the PK-A phosphorylatable serine (Ala-278 in v-Rel; Glu-269 in c-Rel), is mainly responsible for the lack of an effect on DNA binding by v-Rel when Ser-275 is replaced by alanine. That is, a v Rel double mutant (v-275A/278E) showed reduced DNA-binding and transforming abilities as compared with v-Rel and v-275A. Similarly, the mutations in c-Rel that affected DNA binding showed a corresponding effect on the ability of c-Rel proteins to activate transcription in yeast from a reporter gene containing upstream Rel binding sites.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8437856 TI - BM2L is a spontaneous leukemogenic variant of a non-leukemogenic v-myb transformed myeloid cell line. AB - Leukemogenesis is a complex process involving an accumulation of genetic lesions affecting both growth and differentiation in cells of the hematopoietic lineage. Our laboratory has established a non-producer v-myb-transformed cell line (BM2/C3A) which, when injected into the chicken embryo, does not produce leukemia. Recently, a spontaneous variant of this cell line, called BM2L, was obtained from in vivo experiments. BM2L produces an acute monoblastic leukemia when injected into the chicken embryo. BM2L cells do not differentiate in vivo or in vitro, but continue to proliferate under conditions in culture that allow for the differentiation of BM2/C3A cells into macrophages. In addition, BM2L cells have reduced requirements for exogenous growth factors. BM2L cells contain the v myb allele and express v-Myb protein, but leukemogenicity does not involve point mutations in v-myb. The BM2 model, consisting of two non-producer cell lines differing in vivo in their leukemogenicity, provides a novel system for identifying genes that play a role in the induction or suppression of leukemogenesis. PMID- 8437857 TI - Leukemogenicity of v-myb-transformed monoblasts cells can be modulated by normal bone marrow environment. AB - The avian myeloblastosis virus (AMV) causes monoblastic leukemia in the chick. Two non-producer clones of AMV-transformed monoblasts, BM2/C3A and BM2L/A2B5, have been described (see Bottazzi et al., this issue). They differ in their growth requirements and in their ability to induce leukemia when injected into the chick embryo. We first genetically tagged these clones by retroviral infection with a vector expressing the bacterial lacZ gene. Then, we injected the lacZ-positive cells via the chorioallantoic vein into chick embryos. With BM2L/A2B5 cells, the bone marrow of the injected birds was rapidly invaded by lacZ-positive cells. In addition, these cells rapidly overgrew cultures of bone marrow cells derived from injected animals. Conversely, the growth of BM2/C3A was inhibited in the injected animals and only a few blue cells, with the morphology of macrophages, were detected in cultures of bone marrow cells. We developed an in vitro assay to mimic in vitro the differential growth of BM2/C3A and BM2L/A2B5 observed in vivo. These data strongly suggest that BM2/C3A cells retain their ability to differentiate into macrophages in the normal bone marrow environment and that BM2L/A2B5 cells differ from BMC/C3A in the loss of this capacity. PMID- 8437858 TI - Structure, expression and chromosomal mapping of c-akt: relationship to v-akt and its implications. AB - Sequence analysis of a nearly full-length murine c-akt cDNA clone and comparison with v-akt revealed the following: (a) The entire coding region of c-akt is identical to that of v-akt with the exception of five G to A transitions that do not alter the reading frame. The 3' untranslated regions of v-akt and c-akt are also identical with the exception of three single-base differences. (b) The recombination event that gave rise to v-akt occurred between the virus at nucleotide 785 from the Gag ATG codon and the 5' untranslated region of c-akt to 60 bp 5' from the c-akt ATG codon. (c) Three nucleotides absent from both Gag and c-akt were inserted at the junction between the two genes. The outcome of these events was to place, in frame, a 63-bp fragment between Gag and Akt. The resulting v-akt oncogene is predicted to encode a tripartite Gag (p12, p15, delta p30)-X-c-akt protein product. The c-akt protein contains, starting from its amino terminus, a src homology 2-like (SH2-like) domain, a domain rich in glutamic acid residues, part of which is predicted to form an amphipathic helix, and a kinase domain encoding a serine-threonine kinase with high degree of homology to members of the protein kinase C (PKC) family. The mouse c-akt is 90% homologous to human AKT1/RAC at the nucleic acid level and 98% homologous at the amino acid level. c akt in the mouse is composed of 13 exons. The first exon contains a 5' untranslated GC-rich region. Since the recombination that gave rise to v-akt occurred with the 5' untranslated region, we hypothesize that the transduction of c-akt was preceded by provirus insertion upstream from or within the 5' untranslated region and in the same transcriptional orientation as the gene. c akt was mapped by fluorescence in situ hybridization (FISH) to mouse chromosome 12 and rat chromosome 6 in close proximity to the Igh locus. PMID- 8437859 TI - Severely decreased MARCKS expression correlates with ras reversion but not with mitogenic responsiveness. AB - Phorbol ester-inducible phosphorylation of MARCKS, the '80-kDa' substrate of protein kinase C, was undetectable in several phenotypically dominant, non transformed revertants independently derived from the ras-transformed cell line NIH3T3 DT-ras. Extremely low expression of MARCKS protein accounted for this apparent lack of phosphorylation. MARCKS-encoding mRNA levels were correspondingly decreased relative to normal and ras-transformed cells in all four ras revertant cell lines studied: C-11 and F-2, derived by 5-azacytidine treatment and selection with ouabain; CHP 9CJ, derived by ethylmethane sulfonate mutagenesis and selection with cis-hydroxy-L-proline; and 12-V3, derived by transfection with the human Krev-1 gene. However, re-expression of MARCKS after transfection of a cloned MARCKS cDNA into the C-11 ras revertant cells was not sufficient to induce retransformation. In fact, no significant difference in sensitivity to mitogenic stimulation by phorbol esters was observed among several cell lines expressing widely varying levels of MARCKS. This evidence argues against a direct role for MARCKS in mitogenic signaling. However, the strong correlation between attenuation of MARCIS expression and phenotypically dominant ras reversion suggests that a common negative regulatory mechanism might be responsible for both effects, presenting a potentially useful strategy for identifying factors involved in transducing the ras signal. PMID- 8437860 TI - Analysis of the neurofibromatosis type 1 (NF1) GAP-related domain by site directed mutagenesis. AB - The gene for von Recklinghausen neurofibromatosis type 1 (NF1) was recently identified by positional cloning and found to encode a protein with sequence similarity to a family of eucaryotic GTPase-activating proteins (GAPs). Expression of the NF1-GAP-related domain (NF1GRD) has been shown to complement yeast strains deficient in the yeast GAP homologs, IRA1 and IRA2, to interact with human RAS proteins and to accelerate the conversion of ras-GTP to ras-GDP. Further analysis of this region has revealed a number of residues that are highly conserved between members of the GAP family. Mutational analysis of a representative number of these residues produced one of three effects: (1) no change in NF1GRD function, (2) complete disruption of NF1GRD function and (3) intermediate retention of NF1GRD function. One of these mutations at residue 1423 was shown to have reduced ability to negatively regulate ras in yeast, which is interesting in light of a recent report demonstrating a similar naturally occurring mutation in human malignancies. PMID- 8437862 TI - Allele loss patterns on chromosome 17q in 109 breast carcinomas indicate at least two distinct target regions. AB - Loss of heterozygosity (LOH) of markers for chromosome 17 is the most frequent genetic change observed in breast cancer to date. To assess whether the location of several candidate target genes is compatible with patterns of allele losses in the individual tumors, we examined the LOH status of chromosome 17 in 109 primary breast tumors with 15 polymorphic DNA markers (three for 17p and 12 for 17q). Allelic imbalance (AI) at 17q was observed in 44 of the 97 informative cases. A significant correlation was found between AI at the long arm and AI at the short arm of chromosome 17. The patterns of AI on 17q in the tumors differed and were highly complex in some cases. A number of tumors showed AI distal to the growth hormone locus, whereas others showed AI exclusively proximal of this marker. These results indicate that there are at least two different regions of allele loss on 17q. PMID- 8437861 TI - c-Ets-1 protein is hyperphosphorylated during mitosis. AB - The ets-1 and ets-2 proto-oncogene products can serve as transcription factors and become phosphorylated in response to Ca(2+)-mediated signals. We have examined expression of Ets proteins during the cell cycle in cells synchronized by centrifugal elutriation or nocodazole-induced mitotic block. Both methods revealed the presence of a hyperphosphorylated isoform of Ets-1 during the mitotic phase. This isoform showed a characteristic mobility shift and was observed during mitosis in each of four cell lines (three human T-cell lines and a human astrocytoma) that express ets-1. In elutriated cells, only a small portion of the Ets-1 in cells from the G2/M fractions was hyperphosphorylated, while in nocodazole-arrested cells more of the Ets-1 was shifted. When cells were released from nocodazole arrest, this isoform disappeared within 1-2 h as cells completed mitosis and entered G1. This suggests that hyperphosphorylated Ets-1 is present transiently during early mitosis, before or around the time of the metaphase-anaphase transition. Exposure of unsynchronized cells to okadaic acid resulted in a dramatic hyperphosphorylation of virtually all Ets-1, suggesting that changes in cellular phosphatase activity are important for cell cycle regulation of Ets-1. Hyperphosphorylated Ets-1 appears to arise from multiple phosphorylations on serine in the exon 7-encoded domain of the protein and did not appear to alter sequence-specific DNA-binding activity. Although enhanced phosphorylation of Ets-2 was detected in nocodazole-arrested cells, no Ets-2 hyperphosphorylation was seen. PMID- 8437863 TI - Nasopharyngeal carcinoma shows no detectable retinoblastoma susceptibility gene alterations. AB - Since multistage carcinogenesis is frequently associated with the loss of suppressor gene activity, and since in over 90% of cases of nasopharyngeal carcinoma (NPC) p53 alterations are not involved [Sun, Y., Hegamyer, G.H., Cheng, Y.-J., Hildesheim, A., Chen, J.-Y., Chen, I.-H., Cao, Y., Yao, K.-T. & Colburn, N.H. (1992). Proc. Natl. Acad. Sci. USA, 89, 6516-6520] we investigated the possible involvement of the inactivation of the retinoblastoma susceptibility gene (RB) in nasopharyngeal carcinogenesis. We analysed the expression, gross structure and possible point mutation of the RB gene in an NPC cell line as well as seven NPC biopsies obtained from seven patients. The NPC cell line expresses the RB gene with a normal size and abundance, as assayed by reverse transcriptase polymerase chain reaction (RT-PCR) and Northern hybridization. No point mutation was detected in two independent E1A/large T-binding regions, which are the common sites for mutations in the RB gene. NPC biopsies also showed no point mutations at four exon-intron boundaries at which point mutations have been reported in other human carcinomas. The biopsies and cell line had no deletions in the promoter region of the gene and showed no gross deletions or rearrangements. Taken together, we conclude that, in contrast to multistage carcinogenesis leading to human retinoblastoma, osteogenic sarcomas and carcinomas of lung, breast, bladder and prostate, nasopharyngeal carcinogenesis appears unlikely to involve RB gene alterations. PMID- 8437864 TI - Genomic structure, cDNA sequence, and expression of gly96, a growth factor inducible immediate-early gene encoding a short-lived glycosylated protein. AB - We report the cDNA sequence and genomic structure of gly96, an immediate early gene inducible by serum growth factors in mouse fibroblasts. It encodes a 153 amino acid protein that does not share significant sequence similarity with any known protein. In the adult mouse, gly96 is expressed predominantly in the lung, testes and the uterus. We have identified the Gly96 protein in Balb/c 3T3 cells using affinity-purified antibodies recognizing the Gly96 polypeptide. We show that Gly96 is glycosylated and has a short half-life in serum stimulated fibroblasts. PMID- 8437865 TI - Ha-Ras functions downstream from protein kinase C in v-Fps-induced gene expression mediated by TPA response elements. AB - v-Fps activates promoters under the control of the 12-O-tetradecanoyl phorbol 13 acetate (TPA) response element (TRE). The induction of TRE-mediated transcription by v-Fps was sensitive to a dominant-negative mutant of Ha-Ras. An activated derivative of Ha-Ras, v-Ha-Ras, also activated TRE-mediated transcription. v-Fps induced TRE-mediated gene expression was sensitive to depleting cells of protein kinase C (PKC), whereas v-Ha-Ras-induced TRE-mediated transcription was insensitive to PKC depletion, suggesting that Ha-Ras functions downstream from PKC in v-Fps-induced TRE-mediated gene expression. Consistent with this hypothesis, the induction of TRE-mediated gene expression by phorbol esters that activate PKC directly was blocked by the dominant-negative Ha-Ras mutant. Thus, v Fps-induced activation of TRE-mediated gene expression is via an intracellular signaling mechanism that is dependent upon both PKC and Ha-Ras and Ha-Ras functions downstream from PKC. PMID- 8437866 TI - Isolation of PEBP2 alpha B cDNA representing the mouse homolog of human acute myeloid leukemia gene, AML1. AB - Breakpoints of the t(8;21) chromosome translocation in acute myeloid leukemia are clustered within the human gene, AML1, located on chromosome 21 [Miyoshi, H., Shimizu, K., Maseki, N., Kaneko, Y. & Ohki, M. (1991). Proc. Natl. Acad. Sci. USA, 88, 10431-10434]. The product of AML1 has a region about 130 amino acids long that is highly homologous to the Drosophila segmentation gene runt (runt homology region). The cDNA isolated from mouse fibroblasts encoding the alpha subunit of polyomavirus enhancer binding protein 2 (PEBP2/PEA2) revealed that it also has a runt homology region (E. Ogawa et al., submitted). In this study, a different cDNA clone presumed to represent the mouse homolog of human AML1 (PEBP2 alpha B) was isolated from a cDNA library derived from B cells. The deduced amino acid sequence of PEBP2 alpha B is 99% identical to that of AML1 for the first 241 residues, including the runt homology region, though their sequences diverge thereafter. On the other hand, PEBP2 alpha B and PEBP2 alpha share only 92% and 82% homologies at the amino acid and nucleotide levels respectively, even for the runt homology region, indicating that these proteins are encoded by distinct genes. While PEBP2 alpha is highly expressed in T-cell lines but not in most of the B-cell lines and functions as an activator of T-cell-specific genes, PEBP2 alpha B is expressed in both types of cells. A possible functional relationship between PEBP2 alpha and PEBP2 alpha B is discussed in relation to leukemogenic potential of AML1. PMID- 8437867 TI - An algorithm for the management of acoustic neuromas regarding age, hearing, tumor size, and symptoms. AB - An algorithm has evolved for the management of patients with acoustic neuroma. Decisions as to surgery vs. observation, surgical approach, and whether hearing preservation should be attempted depend on age, patient symptoms, size of the tumor, residual hearing, and degree of facial nerve involvement at the time of surgery. Conservative management is used for patients over 65 years of age. This consists of observation or subtotal resection through a translabyrinthine approach, depending on the absence or presence of brainstem signs or symptoms. In patients under 65 years of age, hearing preservation is attempted through the retrosigmoid approach in tumors 1.5 cm or less if pure-tone average is less than 30 dB and the discrimination score is greater than 70%. The translabyrinthine approach is our preferred approach for tumors of any size when hearing is not serviceable. A near-total excision is performed when the facial nerve cannot be separated from the tumor. The rationale for this algorithm in the management of 130 cases of acoustic neuroma over the past 17 years is presented. PMID- 8437868 TI - Progressive hemifacial atrophy. PMID- 8437869 TI - Paratracheal lymph node dissection for carcinoma of the larynx, hypopharynx, and cervical esophagus. AB - Paratracheal lymph node (PTLN) metastasis has been implicated as an etiologic factor in peristomal recurrence after laryngectomy. To determine the relationship between the primary site, the risk of peristomal recurrence, and the prognostic significance of PTLN metastasis, the medical records of 645 patients who underwent total laryngectomy between 1978 and 1990 for squamous cell carcinoma of the larynx, hypopharynx, and cervical esophagus were reviewed. Criteria for inclusion were the surgeon's description of PTLN dissection and hemi- or total thyroidectomy, as well as gross and microscopic pathologic identification of PTLNs. These requirements were fulfilled in 141 patients, who composed the cohort analyzed. There were 117 males and 24 females, with a median followup of 20 months (range, 1 to 94 months). Fifty-three patients were treated previously; among these, 21 underwent tracheostomy before laryngectomy. The primary site of origin was the larynx in 64.5% of patients, the hypopharynx in 25.5%, and the cervical esophagus in 9.9%. Of the patients with endolaryngeal primary tumors, 33% had subglottic extension. Postoperative stomal irradiation was administered to 61 patients. The mean number of PTLNs removed was 3.9 (range, 1 to 30), and metastasis was present in 29 patients (20.5%). PTLN metastasis by primary tumor site was the cervical esophagus, 10 of 14 (71.4%) (p < 0.001); the larynx, 16 of 91 (17.6%); and the hypopharynx, 3 of 36 (8.3%). Of the 30 patients with subglottic extension, eight (26.7%) had PTLN metastases. Peristomal recurrences developed in six of 141 patients (4%), and metastasis to PTLNs was identified in one third of these patients. No peristomal recurrence developed in any of the patients who received postoperative radiotherapy to the stoma (p = 0.057). Survival was significantly reduced by the presence of PTLN metastases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8437870 TI - Intramuscular hemangioma of the head and neck. AB - Intramuscular hemangiomas (IMH) are uncommon tumors in the head and neck region, occurring most often in the trunk and extremities. Preoperative misdiagnosis is common because of the deep location of these tumors. Ten recent cases of head and neck IMH are presented, five of which involve the masseter muscle--the most frequent site of involvement in the head and neck. Masseter IMH occurred almost exclusively in the pediatric age group. The clinical presentation, radiographic and histologic findings, treatment, complications, and outcome of these patients are presented. The vital role of preoperative diagnosis using magnetic resonance imaging (MRI) is discussed, as well as a review of the natural history of IMH and indications for surgical intervention. PMID- 8437871 TI - Clinical evaluation of the monothermal caloric test. AB - The Torok Monothermal Caloric Test has been described as offering a strong advantage over bithermal caloric testing because it can distinguish labyrinthine from retrolabyrinthine lesions. Weak and strong irrigations of room-temperature water are administered to each ear and the ratios of strong to weak nystagmus responses compared to those of normal individuals. Ratios that fall below normal are said to represent decruitment and to denote retrolabyrinthine disease. Ratios that exceed normal are said to represent recruitment and to denote labyrinthine lesions. We attempted to verify the clinical value of the Monothermal Caloric Test by examining patients with known labyrinthine (N = 9) and retrolabyrinthine (N = 25) lesions. Ten patients with dysequilibrium and nonlocalizing testing were also examined. The test was performed exactly as described by the originator. Decruitment was found either unilaterally or bilaterally in 56% of patients with retrolabyrinthine lesions. However, it occurred on the side of the lesion in only 42%. Decruitment was also found in 47% of patients without retrolabyrinthine lesions, including 63% of those with unilateral Meniere's disease. Recruitment was never found on the side of a labyrinthine lesion. A description of the test and a summary of our results are presented. We conclude that the Monothermal Caloric Test is moderately sensitive to the presence of retrolabyrinthine lesions, but lateralizes poorly and is not highly selective. The test was found to be insensitive to the presence of labyrinthine disease. PMID- 8437872 TI - Radiographic imaging of sinusitis in HIV infection. AB - Magnetic resonance images (MRI) of the brain from 75 homosexual men were reviewed to evaluate the frequency and severity of incidental sinus disease associated with human immunodeficiency virus (HIV). All scans had been performed for reasons other than a history of sinus disease. The opacification of each sinus cavity was scored such that 0 = normal, 1 = < 25%, 2 = 25% to 75%, and 3 = > 75% opacification. Subjects were then stratified by clinical status into four groups: HIV-, HIV+ without HIV-related symptoms, AIDS-related complex (ARC), or AIDS. Grade 1 mucosal thickening was present in 52% to 55% of HIV- and HIV+ subjects alike. Moderate disease (grade 2 or 3) was seen in seven of 52 HIV+ subjects, but none of the 23 HIV- controls. The incidence of maxillary sinus thickening was 69% in men with AIDS, compared to 30% in HIV- men (chi 2 = 4.1, p < 0.05). Mean maxillary sinus scores were 1.25 +/- 0.29 in those with AIDS compared to 0.43 +/- 0.15 in HIV- men (f = 5.11, p < 0.05). Our results suggest that maxillary sinus disease is more common and more severe in patients who have AIDS. PMID- 8437873 TI - Pathology of labial salivary gland cellular aggregates in Sjogren's syndrome. AB - Sjogren's syndrome (SS) is a chronic autoimmune inflammatory disease in which lymphocytic infiltration of the lacrimal and salivary glands is the hallmark of disease diagnosis. The present study was conducted to identify developmental features of labial salivary gland histopathology to permit earlier diagnosis of SS patients with borderline biopsies. Control subjects were chosen on the basis of clinical presentation consistent with SS, but whose biopsies did not meet current focus score criteria. Intraglandular connective tissue and diffuse cellular infiltration were significantly greater in SS patients than in controls. Glands in both groups had small cellular aggregates (10 to 50 cells/100 microns2), but those in SS patients were more numerous, larger, and contained more lymphocytes, plasma cells, and active fibroblasts. The large inflammatory foci characteristic of SS appeared to be formed by the enlargement and merging of these aggregates. This suggested aggregate formation was the earliest stage of pathology. Therefore, a comprehensive analysis of these cellular aggregates in borderline or negative biopsies could identify at-risk patients and lead to earlier diagnosis and intervention in the disease. PMID- 8437874 TI - Autologous, orthotopic thyroid follicular cell transplantation: a surgical component of ex vivo somatic gene therapy. AB - Ex vivo strategies for somatic gene therapy involve the harvest of primary cells from patients, the transfer of novel genetic material into these cells in cell culture, and reimplantation of the genetically engineered cells back into patients. In consideration of methods for targeting somatic gene therapy to the thyroid, we have studied the autologous, orthotopic transplantation of thyroid follicular cells in a canine model. Using the fluorescent dye Dil, we were able to stain follicular cells in vitro before transplantation and then follow the pattern of engraftment through histologic sectioning and microscopy up to 14 days after transplantation. The transplantations involved the direct injection of intact and disrupted follicles into a remaining thyroid lobe after cell harvest from the contralateral lobe. We also demonstrated engraftment of individual follicular cells recovered from primary monolayer cultures. Histologic studies revealed the presence of transplanted cells and follicles as well as focal regions of granulomatous reaction in close relation to the engrafted material. These studies demonstrate the feasibility of autologous, orthotopic transplantation of thyroid follicular cells. This method is an essential component of ex vivo strategies for targeting somatic gene therapy to the thyroid gland. PMID- 8437875 TI - Lateral division of the rabbit cricoid cartilage: its effect on cartilage growth. AB - Laryngotracheoplasty often includes bilateral lateral division of the cricoid cartilage, despite the theoretical risk that cartilage growth centers might be located in the lateral cricoid. To investigate the effect of lateral cricoid cartilage division on subsequent cartilage growth, 60 five-week-old New Zealand white rabbits were divided into four groups of 15 animals each. Group I was comprised of unoperated controls. The remaining animals underwent anterior (group II), anterior and posterior (group III), and anterior, posterior, and bilateral lateral (group IV) division of the cricoid cartilage. Animals were killed 20 weeks after surgery, and the cross-sectional area of each animal's cricoid cartilage and of each animal's airway was determined. There was no statistically significant difference in mean cartilage cross-sectional area between any of the four groups; the group IV mean was larger than that of any other group, though the difference was not significant. There was no significant difference in airway cross-sectional area between any of the groups operated on. From these results, lateral cricoid division in the growing animal does not appear to interfere with subsequent normal growth of the larynx. PMID- 8437876 TI - Impedance audiometry and iatrogenic hearing loss. PMID- 8437877 TI - Actinomycosis of the external auditory canal. PMID- 8437878 TI - Neurilemmoma (schwannoma) of the facial nerve presenting as a parotid mass. PMID- 8437879 TI - Aggressive papillary tumors of temporal bone. PMID- 8437880 TI - Bilateral idiopathic aneurysms of the lingual arteries. PMID- 8437881 TI - Surgical glove perforations in otolaryngology: prevention with cut-resistant gloves. AB - This study examines the role of cut-resistant, "orthopedic-type" gloves in prevention of exposure of surgical personnel to infectious body fluids through surgical glove perforation. The incidence of glove perforations in 12 consecutive cases of intermaxillary fixation (IMF) was studied. Surgeons were double-gloved with standard latex gloves and wore cut-resistant gloves between the outer and inner gloves. As controls, six cadaver heads were wired into IMF with surgeons double-gloving without the cut-resistant glove. The rates of latex glove perforation were then compared between the two groups. Fifty-three percent (32 of 60) of outer latex gloves, but no inner latex gloves (0 of 50) were perforated when surgeons wore cut-resistant gloves. In the control group, 45% of outer gloves (9 of 20) and 15% of inner gloves (3 of 20) were perforated. The difference of inner glove perforations--hence cutaneous exposure--between these two groups was statistically significant (p < 0.01). The use of cut-resistant gloves in addition to double-gloving with latex surgical gloves is recommended for facial plastic and reconstructive procedures with metal implants and major head and neck surgery, because these operations have a high rate of glove perforation. Because some loss of dexterity is noted when cut-resistant gloves are worn, the risk of glove perforation must be weighted against the need for optimal dexterity. PMID- 8437882 TI - A new endotracheal tube for carbon dioxide and KTP laser surgery of the aerodigestive tract. AB - We have tested the fire-resistance of a new endotracheal tube designed for use in laser surgery of the upper aerodigestive tract. This Teflon/metallic-wrapped silicone tube seems capable of withstanding occasional, accidental pulsed laser impact at power settings used clinically (1 to 10 watts) without fire. On rare occasions when continuous mode is used, the tube seems capable of withstanding at least several seconds of continuous irradiation at clinical power settings without igniting. When used with other recommended safety procedures, this tube should minimize the risk of endotracheal tube fire from accidental laser impact. PMID- 8437884 TI - Mechanical modulation of a voltage-dependent non-inactivating K+ current in cultured bullfrog sympathetic neurones. AB - Cultured bullfrog sympathetic ganglion cells were voltage-clamped with a whole cell patch-clamp technique. Local flow of a solution (identical to the bathing solution) from a micropipette to a cell, but not other mechanical stimuli, produced a non-inactivating outward (in 34 cells out of 141) or inward (in 70 cells) current [I(f)(out) or I(f)(in), respectively] depending on cells. Both I(f)(out) and I(f)(in) appeared at voltages more positive than -60 mV. The mechanism, however, was activated even at -70 mV, as I(f)(out) or I(f)(in) appeared on shifting membrane potential to -30 mV immediately after the local flow. I(f)(out) and I(f)(in) were accompanied by increases and decreases, respectively, in the membrane conductance and current relaxation to a voltage jump between -30 mV and -55 mV without a change in its time constant (whose value was similar to that of a voltage-dependent non-inactivating K+ current, IM), and reversed at a membrane potential close to the equilibrium potential for K+. Both I(f)(out) and I(f)(in) were blocked by Ba2+ (4-8 mM), a blocker of IM, and by muscarine (10 microM), which produced either an "apparent inward" or outward current. A transient outward current activated by a voltage jump from -85 mV (or 75 mV) to -30 mV was little affected by a local flow of a solution which produced I(f)(out) or I(f)(in). These results suggest that the local solution flow produced I(f)(in) or I(f)(out) by deactivating or activating IM, respectively. PMID- 8437883 TI - Spontaneous calcium oscillations and mechanically and chemically induced calcium responses in mammary epithelial cells. AB - Changes of intracellular calcium activity (Ca2+i) in mouse mammary epithelial cells in primary culture (normal) and in an established cell line (MMT060562, cancerous) were investigated by microfluorometry and image analysis of fura-2 fluorescence. In both types of cells, some populations exhibited occasional Ca2+i oscillations with a period of 50-160 s. Slight mechanical stimulation of a cell with a fine glass pipette induced a Ca2+i increase, which spread from the stimulated cell to the surrounding cells with a speed of 7-12 microns/s. ATP (> 1 mumol/l) and ADP, but not AMP induced a Ca2+i increase in both cell types. Bradykinin was highly effective (> 10 nmol/l) only in the cancerous mammary epithelial cells. In Ca(2+)-free solution, all these Ca2+i responses remained unchanged at the first application, and decreased abruptly at the second trial. La3+ (> 0.5 mmol/l) suppressed the response to ATP but not the response to bradykinin. Addition of extracellular Mn2+ rapidly quenched the fura-2 fluorescence in the cell even in a non-stimulated state. Influx of Mn2+ did not increase during Ca2+i responses. These results indicate that the sources of Ca2+i responses in mammary epithelial cells are intracellular stores, which exchange Ca2+ with the extracellular medium. PMID- 8437885 TI - Effect of endurance training on angiogenic activity in skeletal muscles. AB - The effect of endurance training on angiogenic activity in skeletal muscle was investigated using cell culture. The exercised rats were trained on a rodent treadmill, 5 days a week for 9 weeks. After the training program, a significant increase (7.8%) in mass was found in soleus muscle (MS), although we noted no apparent increase in gastrocnemius muscle and extensor digitorum longus muscle. The extracts from all the muscles (especially from the MS) of trained rats considerably increased the capillary growth in an in vitro angiogenesis model, in which microvascular fragments and myofibroblastic (Mf) cells isolated from lipid tissues were grown in co-culture. In addition, the extract from the MS of trained rats increased the DNA synthesis and growth of bovine capillary endothelial (BCE) cells, although the extract did not stimulate the growth of Mf cells. Moreover, the extract from the MS of trained rats notably enhanced the activity of plasminogen activator in the conditioned medium of BCE cells compared with that of sedentary rats. On the other hand, extracts from the MS of both sedentary and trained rats increased the synthesis of collagen by Mf cells and metalloproteinase activity in the conditioned medium of BCE cells to the same degree. These results suggest that endurance training increases the angiogenic activity in skeletal muscles. PMID- 8437886 TI - Inactivation determined by a single site in K+ pores. AB - An N-terminus peptide or a C-terminus mechanism involving a single residue in transmembrane segment 6 produces inactivation in voltage-dependent K+ channels. Here we show that a single position in the pore of K+ channels can produce inactivation having characteristics distinct from either N- or C-type inactivation. In a chimeric K+ channel (CHM), the point reversion CHM V369K produced fast inactivation and CHM V369S had the additional effect of halving K+ conductance consistent with a position in the pore. The result was not restricted to CHM; mutating position 369 in the naturally occurring channel Kv2.1 also produced fast inactivation. Like N- and C-types of inactivation, pore or P-type inactivation was characterized by short bursts terminated by rapid entry into the inactivated state. Unlike C-type inactivation, in which external tetraethylammonium (TEA) produced a simple blockade that slowed inactivation and reduced currents, in P-type inactivation external TEA increased currents. Unlike N-type inactivation, internal TEA produced a simple reduction in current and K+ occupancy of the pore had no effect. External TEA was not the only cation to increase current; external K+ enhanced channel availability and recovery from inactivation. Additional features of P-type inactivation were residue-specific effects on the extent of inactivation and removal of inactivation by a point reversion at position 374, which also regulates conductance. The demonstration of P-type inactivation indicates that pore residues in K+ channels may be part of the inactivation gating machinery. PMID- 8437888 TI - Contribution of potassium accumulation in narrow extracellular spaces to the genesis of nicorandil-induced large inward tail current in guinea-pig ventricular cells. AB - The mechanism of nicorandil-induced large inward tail current (Itail) in single guinea-pig ventricular cells was investigated using the whole-cell patch-clamp technique. In the presence of 0.5-1.0 mM nicorandil, an activator of adenosine 5' triphosphate (ATP)-sensitive K+ current (IKATP), a depolarization pulse causing a large outward current was followed by a large inward Itail on the repolarization step to the holding potential at -85 mV. The larger the outward current, the greater the Itail. The amplitude of Itail increased as a single exponential function (tau = 74.9 ms) as the duration of preceding depolarization was prolonged. Both the outward current and Itail were inhibited nearly completely after application of glibenclamide (1 microM), a specific blocker of IKATP. Substitution of K+ with Cs+ in both the external and internal solutions resulted in a virtual elimination of Itail. Itail was well preserved under the condition where Ca2+ entry during the preceding depolarization was largely inhibited or where external Na+ was replaced by Li+. A transient positive shift of reversal potential for the net current was observed at the peak of Itail). At 30 mM external K+ concentration, Itail was almost eliminated. From these findings, its is concluded that the Itail is a K+ current associated with an alteration of the K+ equilibrium potential (EK) following a substantial K+ efflux. This EK change is most likely explained by an accumulation of K+ in transverse tubules (T tubules) since Itail was not induced in atrial cells in which T-tubules are poorly developed. PMID- 8437887 TI - Agonist-induced inhibition of inositol-trisphosphate-activated IK(Ca) in NG108-15 neuroblastoma hybrid cells. AB - IK(Ca) activated by intracellular ionophoresis of inositol trisphosphate (IP3) or pressure-applied acetylcholine was inhibited by bradykinin and acetylcholine in NG108-15 cells transfected with m1 receptors. The inhibition of the IP3-evoked current was complete at 10 microM acetylcholine. This inhibition was not seen if the current was evoked by intracellular ionophoresis of calcium ions. Only receptors the activate the phosphoinositide system in these cells produced this inhibition, i.e. transfected muscarinic m1 and m3 and bradykinin receptors, but not muscarinic m2, m4 or adrenergic alpha 2 receptors. This inhibition was not sensitive to pertussis toxin or staurosporine. The concentrations of acetylcholine needed to inhibit the evoked current were identical to those needed to raise intracellular calcium but tenfold less than those needed for the agonist to activate IK(Ca). In a normal calcium-containing superfusate, recovery from inhibition required around 8 min (half-time 4 min) after removal of acetylcholine. When the experiment was performed in calcium-free medium no recovery was seen after 8 min washing in drug-free solution, but complete recovery was seen within 3 min (half-time 1.5 min) after adding calcium. Responses to repeated pressure applications of acetylcholine could be reversibly inhibited by acetylcholine and bradykinin. It seems, then, that there is no direct action of acetylcholine or bradykinin on the IK(Ca) channels themselves but that concentrations below those needed to activate IK(Ca) can empty and inhibit the IP3-sensitive calcium store. This may provide a mechanism for heterologous desensitization for phospholipase-C-linked receptor-mediated responses. PMID- 8437889 TI - Central and peripheral contributions to control of heart rate during heat acclimation. AB - The contributions of the autonomic nervous system and the cardiac pacing cells in the development of heat-acclimation-induced bradycardia were analyzed, and the effect of heat acclimation on the chronotropic response of the heart to heat stress (40 degrees C) was studied. Rats were acclimated at 34 degrees C for 0, 5, 14, 30 and 60 days. Heart rate (HR) was measured in conscious animals, using chronic subcutaneous electrodes. Sympathetic and parasympathetic influences were studied by IP administration of 0.1 and 1 mg/100 g body weight atropine and propranolol respectively, while intrinsic HR (HRi) was measured following administration of both drugs simultaneously. The effects of carbamylcholine and norepinephrine on the beating rate of isolated rat atria were investigated to study pacemaker responsiveness to neutrotransmitters. Up to day 14 of heat acclimation, bradycardia was attained by tonic parasympathetic acceleration (18%) and temporal sympathetic withdrawal (0.8% on day 14), to compensate for the gradually augmented HRi (2.5% and 8% on days 5 and 14, respectively). Following long-term acclimation HRi declined below pre-acclimation rate. This was associated with resumed sympathetic activity (16% and 10% on days 30 and 60 respectively) while parasympathetic activity continued to be high (18%). Tachycardia, known to occur with severe uncontrolled body hyperthermia, was attenuated following heat acclimation by 42%. It was concluded that during the initial phase of heat acclimation bradycardia is achieved primarily by changes in autonomic influences, while following long-term acclimation, changes in the intrinsic properties of the pacing cells (HRi) and the autonomic system both play a role. PMID- 8437890 TI - Bradykinin stimulation of electrogenic ion transport in epithelial layers of cultured human endometrium. AB - Primary cultures of glandular endometrial epithelial cells grown on permeable supports formed monolayers with a high transepithelial electrical resistance [1096 +/- 83 omega.cm2 (n = 34)] and displayed electrogenic ion transport as demonstrated by an inward short circuit current (Isc; 20 +/- 2 microA/cm2). Bradykinin, 10(-8)-10(-6) M, added to either the basolateral or apical solutions enhanced the inward ISC. The concentration-response curves for bradykinin were bell-shaped in nature. The ISC response was more sensitive to apical addition of bradykinin and the maximum response was also greater with apical bradykinin. The increases in ISC were accompanied by two- to three-fold increases in transepithelial conductance. Apical addition of amiloride, 10(-4) M, reduced the unstimulated ISC by 80%. In the presence of amiloride, the response to both apical and basolateral bradykinin was reduced by > 50% in 8 out of 18 layers, and the mean response was reduced by approximately 25%. The data are consistent with a physiological role for bradykinin in the control of the intrauterine electrolyte environment, mediated in part by enhanced Na+ absorption. PMID- 8437891 TI - Antioxidant enzyme systems in skeletal muscle atrophied by immobilization. AB - To clarify the mechanism of oxidative stress in skeletal muscle atrophied by immobilization, we investigated the change of antioxidant enzyme activities in a typical slow red muscle, the soleus. Atrophied soleus muscles were collected from male Wistar rats (16 weeks old), one ankle joint of which had been immobilized in the fully extended position for 7 days. Also, soleus muscles were collected from intact age-matched rats as control. The activities of Mn-containing superoxide dismutase (Mn-SOD), Cu,Zn-containing superoxide dismutase (Cu,Zn-SOD), Se dependent glutathione peroxidase (Se-GSHPx), glutathione S-transferase (GST), catalase, and glutathione reductase (GSSGRx) were measured. The activities of Cu,Zn-SOD, GST, and GSSGRx were significantly higher in atrophied muscles, while the others were unchanged. Increased Cu,Zn-SOD and unchanged Mn-SOD levels might reflect increased generation of superoxide anions in the cytoplasm rather than in the mitochondria. Owing to the enhancement of Cu,Zn-SOD and the unaltered Se GSHPx and catalase activities, hydrogen peroxide is thought to be increased in the cytoplasm. Because there is also an increase of iron in the microsomes of atrophied muscles, the production of hydroxyl radicals, the most aggressive of radicals, might consequently be elevated. PMID- 8437892 TI - Non-typical K(+)-current in cesium-loaded guinea pig type I vestibular hair cell. AB - Isolated guinea pig type I vestibular hair cells were voltage clamped at HP-110 mV in whole cell clamp configuration and depolarized up to +20 mV. Increasing depolarizations elicited large outward currents. These currents were replaced, in cesium-loaded cells, by inward/outward currents that reversed at membrane potentials between -55 and -30 mV. The reversal potential varied from cell to cell, and appeared to depend on the intracellular potassium cesium ratio. The current remaining in the presence of intracellular cesium was essentially due to a non-typical potassium conductance, which decreased in the presence of 4-AP and was blocked by 4-AP plus TEA. This current appeared as soon as the membrane was depolarized, showing the high potassium permeability of type I vestibular hair cells. A small part of this current was a strictly calcium inward current, sensitive to flunarizine, with a leakage component in the hyperpolarized state and a voltage component when the cell was depolarized. PMID- 8437893 TI - Gap junctional conductance tunes phase difference of cholecystokinin evoked calcium oscillations in pairs of pancreatic acinar cells. AB - Using the double whole-cell recording technique we measured the gap junctional conductance (gj), while simultaneously monitoring the cytoplasmic free calcium concentration ([Ca2+i]) in isolated acinar cell pairs from the pancreas of mouse. Physiological concentrations of the secretagogue cholecystokinin-octapeptide (CCK OP) elicited [Ca2+i] oscillations and after a delay in the minute range reduced gj. The results provide the first evidence suggesting that gj regulates the phase difference (delta phi) of [Ca2+i] oscillations between neighbouring cells not in an all or none process, but with decreasing absolute value of gj delta phi monotonically increases. CCK-OP induced electrical uncoupling as well as the corresponding increase of delta phi could be blocked completely by the protein kinase C inhibitor polymyxin B. The data support the hypothesis that Ca2+ flow through gap junctions synchronizes [Ca2+i] oscillations between jap junctional coupled cells. PMID- 8437894 TI - Morphological and functional consequences of chronic epilepsy in rat hippocampal slice cultures. AB - We have developed an in vitro model of chronic epilepsy in order to study the consequences of prolonged periods of epileptic activity. After applying the convulsants bicuculline and/or picrotoxin to mature rat hippocampal slice cultures for 3 days, large numbers of swollen and vacuolated cells were observed throughout all hippocampal subfields. The number of dendritic spines of pyramidal cells was massively reduced. These changes were similar to those observed previously in post-mortem studies of hippocampal tissue from human epilepsy patients. Intracellular recordings from CA3 pyramidal cells revealed that spontaneous synaptic activity was greatly reduced in treated cultures. gamma Aminobutyric acid-mediated inhibition was apparently not affected by sustained convulsant activity, although synaptic excitation was markedly depressed. Acute re-application of bicuculline to treated cultures elicited, upon stimulation of the mossy fibre tract, a typical interictal burst lasting several hundred milliseconds, with a wave form similar to those occurring in untreated cultures, but of a shorter duration. In contrast, ictal bursts (lasting tens of seconds), which always occur spontaneously in control cultures during initial perfusion of bicuculline, were not observed in treated cultures. These pathological changes were reversible when treated cultures were returned to normal medium for 1 week. The surviving cells had a healthy morphology and a normal complement of dendritic spines. Spontaneous synaptic activity was normal, and ictal bursts occurred spontaneously upon perfusion of bicuculline. The findings suggest that the morphological and functional changes are a consequence, rather than a direct cause of epilepsy. PMID- 8437895 TI - Nursing Times open learning programme. P11: models for care. Part (ii): Two contrasting nursing models (continuing education credit). PMID- 8437896 TI - Midwifery-led care. PMID- 8437897 TI - Revival tactics. PMID- 8437898 TI - Labour's lost love? PMID- 8437900 TI - Children and death. A cry for help. PMID- 8437899 TI - Children and death. Saying goodbye. PMID- 8437901 TI - Project 2000: back to basics. PMID- 8437902 TI - Immunosuppressive agents. PMID- 8437903 TI - Liver failure in young children. PMID- 8437904 TI - The right fit. PMID- 8437905 TI - Welcome visitor. PMID- 8437906 TI - Value yourself. PMID- 8437907 TI - Munchausen syndrome by proxy. PMID- 8437908 TI - Continence. A testing time. PMID- 8437910 TI - Nursing Times open learning programme. P11: models for care. Part (iii): Your own nursing model (continuing education credit). PMID- 8437909 TI - Continence. Suffering in secret. PMID- 8437911 TI - Prophit and loss. Interview by Daloni Carlisle. PMID- 8437912 TI - Buying-out appeals. PMID- 8437913 TI - After the vote. PMID- 8437914 TI - A double-edged chalice? PMID- 8437915 TI - Community Care Act. Funding the Act. PMID- 8437916 TI - Community Care Act. Managing care at home. PMID- 8437917 TI - Travelling companions. PMID- 8437919 TI - Making sense of shock. PMID- 8437918 TI - In a day's work. PMID- 8437920 TI - Grave new world. PMID- 8437921 TI - Two-way split. PMID- 8437922 TI - Diabetes. Operations manager. PMID- 8437923 TI - Diabetes. Educating experience. PMID- 8437924 TI - Ageing matters. Attitude problem. PMID- 8437925 TI - Ageing matters. Altered images. PMID- 8437926 TI - Nursing Times open learning programme. R5: using research. Part (i): The route from research to practice (continuing education credit). PMID- 8437928 TI - Male rape. PMID- 8437927 TI - Crab lice an indicator of other STDs. PMID- 8437929 TI - System failure? PMID- 8437930 TI - Child benefit. PMID- 8437931 TI - Power of the lobby. PMID- 8437932 TI - Professional development. Survival of the fittest. PMID- 8437933 TI - Professional development. Managing challenge. PMID- 8437935 TI - Community care. The case for supervision. PMID- 8437934 TI - Professional development. Growing pains. PMID- 8437936 TI - Community care. A hindrance to care? PMID- 8437937 TI - Surgery. Transatlantic challenges. PMID- 8437938 TI - Learning revolution. PMID- 8437939 TI - Essential support. PMID- 8437940 TI - Systems of life. The nervous system. 5. PMID- 8437941 TI - Midwives' journal. Male delivery. PMID- 8437942 TI - Midwives' journal. Supporting services. PMID- 8437944 TI - Research module R5: using research. Part (ii): Your role in introducing research. PMID- 8437943 TI - Midwives' journal. Grin and bear it? PMID- 8437945 TI - The magic touch. PMID- 8437946 TI - Working with numbers. PMID- 8437947 TI - The marketing morass. PMID- 8437948 TI - Infection patrol. PMID- 8437950 TI - Get it write. PMID- 8437949 TI - Smoke-screening. PMID- 8437951 TI - Inside story. PMID- 8437952 TI - Non-fiction addiction. PMID- 8437953 TI - Counselling--call for help. PMID- 8437955 TI - Community Care Act. From hospital to community. PMID- 8437954 TI - Sexual health--reaching out. PMID- 8437956 TI - The nursing Princess. PMID- 8437957 TI - The gender trap. PMID- 8437958 TI - Quality assurance--measured pace. PMID- 8437959 TI - Wound care. Prescribing potential. PMID- 8437960 TI - Wound care--practical changes. PMID- 8437961 TI - Wound care--a painful ordeal. PMID- 8437962 TI - Wound care--skin complaint. PMID- 8437963 TI - Measurement of Tc-99m DTPA serum clearance for estimating glomerular filtration rate in children with cancer. AB - Clearance of the radiopharmaceutical Tc-99m DTPA estimated from blood samples with no urine collection can provide a reliable estimate of glomerular filtration rate (GFR) in adults, but has not been well studied in children. The disposition of Tc-99m DTPA was determined in 17 children with cancer, and the influence of binding and study design on the estimates for serum clearance were evaluated. Nine blood samples were obtained over 6 hours in each patient, and serum was assayed for total and free Tc-99m. Free Tc-99m DTPA was determined by ultrafiltration. Estimates of clearance derived from a two-compartment model for ultrafiltrable Tc-99m DTPA were determined from all nine measured concentrations, and these results served as a reference value for GFR in each subject. Total Tc 99m DTPA concentrations also were best described by a two-compartment model, but the median total clearance (35 ml/min) was significantly (p < 0.01) lower than the ultrafiltrate clearance (58 ml/min). The effect of a simplified sampling schedule was assessed from clearance estimates based on a 3-point subset of the ultrafiltrable data. The median clearance of 69 ml/minute was significantly higher (p < 0.01) than the reference GFR. However with a correction factor included to account for the positive bias arising from the limited sampling schedule, the reference estimates for GFR were well predicted (r2 = 0.99) with no significant bias. Ultrafiltrable Tc-99m DTPA serum clearance using a limited sampling schedule can provide a consistent and clinically feasible estimate of glomerular filtration rate in children, but binding in serum and study design are potentially important confounding factors. PMID- 8437964 TI - Growth factors in nutritional support. AB - Protein catabolism occurs in the severely stressed patient despite adequate protein supplementation. Supplementation of endogenous growth factors is one mechanism being evaluated to promote anabolism and improve nitrogen retention. Recombinant technology has provided a means to reproduce these endogenous growth factors. Both recombinant human growth hormone (rGH) and recombinant human insulin-like growth factor-1 (rhlGf-1) are undergoing clinical trials to establish their roles in nutritional support. PMID- 8437965 TI - Pharmacotherapy of preterm labor. AB - Preterm labor is defined as the onset of uterine contractions in a woman who has completed less than 37 weeks of pregnancy. It may be due to maternal, placental, fetal, or idiopathic causes, and it is associated with a number of risk factors. Nondrug measures such as bedrest and hydration have been used alone or in combination with drug therapy to treat the disorder. Pharmacologic (tocolytic) agents include ethanol, progesterone, indomethacin, nifedipine, beta-adrenergic agonists, and magnesium salts. The three most commonly used drugs are ritodrine, terbutaline, and magnesium. PMID- 8437966 TI - Pharmacokinetics and pharmacodynamics of ranitidine and famotidine in healthy elderly subjects: a double-blind, placebo-controlled comparison. AB - The pharmacokinetics and pharmacodynamics of ranitidine and famotidine were studied in 13 healthy elderly volunteers. On 3 mornings separated by a 1-week wash-out period, each subject received a single oral dose of ranitidine 300 mg, famotidine 40 mg, and placebo in a crossover, randomized fashion with double dummy administration. Plasma and urine concentrations of ranitidine and famotidine were determined by high-performance liquid chromatography. Intragastric pH was measured for 24-hours with an antimony probe. Famotidine's plasma half-life (4.42 hrs) was significantly longer than ranitidine's (3.14 hrs, p < 0.05, paired t test). The 24-hour, area under the curve of pH profiles of the two drugs were significantly different from placebo (p < 0.05, analysis of variance and Fisher PLSD test) but not from each other. The duration of effect (defined as median pH > 4) was similar for ranitidine and famotidine, 10.3 and 9.9 hours, respectively (p = 0.713, paired Student's t test). Thus both agents exhibited a similar duration of 24-hour antisecretory response under these study conditions. PMID- 8437967 TI - Omeprazole: a comprehensive review. AB - Omeprazole is a member of a new class of substituted benzimidazoles. These agents inhibit the proton pump in the gastric parietal cell, blocking the final step in the gastric acid secretory pathway. Omeprazole has been investigated for the treatment of gastric ulcer, duodenal ulcer, gastroesophageal reflux, and various hypersecretory states. The prolonged inhibition of gastric acid secretion allows for once-daily dosing in patients with peptic ulcer disease and gastroesophageal reflux, and once- or twice-daily dosing in patients with Zollinger-Ellison syndrome. Compared with currently available therapies, omeprazole is well tolerated and demonstrates a more rapid ulcer healing rate. It is superior to conventional therapies in the treatment of Zollinger-Ellison syndrome. Side effects are infrequent when the drug is used for the short-term management of ulcers. PMID- 8437968 TI - The use of delta osmolality to predict serum isopropanol and acetone concentrations. AB - We investigated whether serum delta osmolality will predict the total serum concentration of isopropanol and acetone metabolite. Three isopropanol ingestions were monitored by delta osmolality determinations followed by quantification of serum isopropanol and acetone concentrations. The delta osmolality was established by routine chemical analysis and standard freezing point depression osmometry. Serum isopropanol and acetone levels were quantified by gas chromatography-head space analysis (GC-HS). Patients were initially suspected of having isopropanol intoxication secondary to an elevated delta osmolality discrepancy (measured - calculated > 10 mOsm). Serum concentrations versus delta osmolality were analyzed by linear regression (correlation coefficient r = 0.713; p < 0.05). The delta osmolality paralleled and decreased relative to the total low molecular weight of volatile concentration in each case. In emergencies, delta osmolality may be a screening test to identify rapidly patients at risk for complications associated with isopropanol ingestion when GC-HS is not available. PMID- 8437969 TI - Sinus arrest associated with continuous-infusion cimetidine. AB - The administration of intermittent intravenous infusions of cimetidine is infrequently associated with the development of bradyarrhythmias. A 40-year-old man with leukemia and no history of cardiac disease developed recurrent, brief episodes of apparent sinus arrest while receiving continuous-infusion cimetidine 50 mg/hour. The arrhythmias were temporally related to cimetidine administration, disappeared after dechallenge, and did not recur during ranitidine treatment. This is the first reported case of sinus arrest associated with continuous infusion cimetidine. PMID- 8437970 TI - Propafenone-theophylline interaction. AB - A 63-year-old man with ventricular tachycardia (VT) refractory to drug therapy was admitted for surgical ablation of the VT with coronary artery bypass graft surgery. He developed increased theophylline concentrations with decreased calculated theophylline clearance after propafenone therapy for recurrent VT was initiated. Within 1 day after the addition of propafenone 150 mg every 8 hours to a drug regimen that included theophylline sustained-release tablets 300 mg every 12 hours, the patient demonstrated increased theophylline serum concentrations and decreased calculated theophylline clearance. Despite a decrease in theophylline dosage, theophylline concentrations continued to rise as the dosage of propafenone was increased to 300 mg every 8 hours. Theophylline was discontinued due to a rising theophylline level, improved oxygenation, and absence of wheezing. Both propafenone and theophylline are hepatically metabolized by the cytochrome P-450 enzyme system. The decrease in theophylline clearance of 25% to 69% in this patient may be due to competitive metabolism resulting in enzyme inhibition and increased theophylline concentrations. Since propafenone and 5-OH-propafenone levels were not measured, it is unknown whether propafenone clearance was affected as well. Health care practitioners should be aware of this possible drug interaction and monitor theophylline concentrations and the electrocardiogram closely if the agents are coadministered. PMID- 8437971 TI - Seizure after lidocaine for bronchoscopy: case report and review of the use of lidocaine in airway anesthesia. AB - Lidocaine-induced seizures have been reported after topical administration. A 30 year-old, 48-kg women with acquired immunodeficiency syndrome, chronic end-stage renal failure, anemia, congestive heart failure (CHF), cardiomyopathy, and increased liver function tests was admitted to the hospital with fever, chills, and dry cough. Bronchoscopy was performed to rule out Pneumocystis carinii pneumonitis; the patient experienced seizure activity after administration of a total dose of topical lidocaine 300 mg. Plasma drug concentration measured shortly after seizure, and at 4 and 22 hours after seizure were 12.0, 7.6, and 1.4 mg/L, respectively. A direct correlation exists between clinical symptoms and blood level of lidocaine; as the level increases to 8-12 mg/L the probability of seizure increases. The extent of absorption and bioavailability after airway administration depends on tissue vascularity, sites and techniques of application, patient's disease state, and, most important, the dose/unit body weight. The lidocaine dose should be titrated slowly and patients monitored for altered mental status. The dose often has to be decreased empirically in patients with liver disease or CHF. Efforts should be made to deliver minimum amounts of the drug to the lower respiratory tract, since its pharmacokinetics at that site are similar to those with intravenous administration. PMID- 8437972 TI - [Diagnosis of right heart stress with one- and two-dimensional echocardiography- sensible normal values, problems and limitations]. AB - Unidimensional and two-dimensional echocardiography is considered to be an established method of examination in cardiology alongside Doppler sonography and the transoesophageal method. It is planned to propagate the use of unidimensional and two-dimensional echocardiography in internistic pneumological diagnostics. To achieve this it is imperative to know the standard values of the right heart and to know how they are to be assessed. The standard values stated so far have proved to be too low in practice, resulting in many false positive findings, and are often also too complicated to obtain. 53 healthy probands were selected at random and six different measurements of the right heart and the efferent major vessels were performed. Only the diameter of the right ventricle and right atrium, as well as the wall thickness of the right ventricular wall were found to be suitable parameters for confirming right ventricular strain. The measured values were tested for reproducibility in patients suffering from diseases of the lung and of the airways. Compared with pressure values of pulmonary circulation obtained by invasive methods, maximum values obtained in patients with pulmonary hypertension can serve to recommend unidimensional and two-dimensional echocardiography as screening method in cases of suspected cor pulmonale. PMID- 8437973 TI - [Intravascular ultrasound in preoperative diagnosis of central bronchial tumors- initial clinical experiences]. AB - In the course of preoperative diagnosis, intravasal sonography for tumour imaging was conducted in three patients suffering from central bronchial carcinoma. The catheters of 6.0 or 4.8 French diameter were advanced in each case after pulmonary angiography via the left or right pulmonary artery up to the tumour area. Endosonographic tumour imaging was compared with the findings of the other preoperative diagnostic measures and in two cases with intraoperative and postoperative findings. The vascular walls of the central pulmonary arterial segments showed sonographically no typical three-layer structure. In all cases, however, tumour infiltration was showed up by disappearance of the vascular wall reflexes in the relevant pulmonary artery branches. Visualisation of the mediastinal pulmonary artery segments or of the main stem of the pulmonary artery is difficult with the wire-guided catheters used, since these cannot be stabilised in the centre of the vessel. Development of suitable catheters with low-frequency transducers and greater depth of penetration is imperative especially for the diagnostically important visualisation of the surrounding mediastinal structures. PMID- 8437974 TI - [Recommendations for long-term oxygen therapy in severe chronic hypoxemia. German Society of Pneumology]. PMID- 8437975 TI - [Patient training in obstructive respiratory tract diseases--the status in Germany]. AB - An analysis of the situation in respect of the activity of the Working Group "Patient Training" of the German Society of Pneumology reveals that the development has been a positive one. During the period under scrutiny (1988-1990) the patient training measures were markedly broadened for patients suffering from obstructive airway diseases. A significant increase took place in specialised hospitals and in the medical practices of physicians. Patients suffering from asthma, chronic obstructive bronchitis and pulmonary emphysema were trained both for coping with their individual diseases and with subsequent and concomitant diseases. On the whole, about 18,000 patients were trained in Germany. Both own material and in an increasing measure material supplied by the pharmaceutical industry was successfully employed. Although most of the trainers are physicians, these are being increasingly joined by nurses and physiotherapists. In the consulting-rooms of practising physicians, patient training is performed mainly up to two hours after consulting hours, especially in the evening. Preferred subjects are technique of inhalation, problems of therapy and causes of airway diseases. Second in importance after the individual talk with the patient is the group discussion. To spread patient training it will be necessary to set up pilot units: however, the medical professional organisations should also help in translating the project into reality. Standardisation of training measures for clinic and practice is planned and will be a future target for the working group. The aim is to officially integrate training measures into the therapeutic concept in obstructive airway disease also for practising physicians. PMID- 8437976 TI - [Tolerance and effect of short-term theophylline infusions]. AB - Short-term infusions with theophylline or aminophylline are often infused very quickly. The present study aimed at comparing the tolerance and therapeutic effect of a theophylline short-term infusion (420 mg theophylline) and an aminophylline short-term infusion (theophylline component 351.3 mg). We infused 16 adults suffering from chronic obstructive respiratory disease, daily at 7 a.m. with increasing speed of infusion and in the following week the other one, and recorded undesirable effects and actions on pulmonary function and gas exchange. 3 of 16 patients tolerated only slow speeds of infusion, 7 patients had mild side effects and tolerated like the other 6 patients even the shortest infusion time. On the whole, both preparations were equally well tolerated. FEV1 and peak flow improved clearly, but only in the course of the next few hours. Theophylline short-term infusion was markedly more effective in this regard. The prompt and infusion rate-independent improvement of the transcutaneous O2 and CO2 partial pressures, which took place even during the short-term injection period, was independent of the preparation. Our data show that intravenously administered theophylline or aminophylline are therapeutically acutely useful substances. However, there is evidently no need to administer theophylline or aminophylline short-term infusions very rapidly, i.e. at below 20 minutes infusion time. PMID- 8437977 TI - [Tuberculosis of the tongue in chronic hematogenous lung tuberculosis]. AB - According to epidemiological data pulmonary and extrapulmonary tuberculosis even today represents a significant socio-medical problem. Tongue tuberculosis is rare and has been described in single cases only. In our clinic a patient suffering from tongue tuberculosis and hematogenously spreading chronic pulmonary tuberculosis was treated for the first time. The diagnosis was made by means of biopsy and pathohistological examination. The tongue lesions on account of rich vascularisation reacted very quickly to the antituberculous therapy, and the pulmonary alterations regressed considerably so that the patient could be dismissed to policlinical treatment. PMID- 8437978 TI - [Respiratory sounds and incidental sounds. Historical review and recommendation for adopting the new 1985 international classification and nomenclature]. PMID- 8437979 TI - Plasminogen and plasminogen activator assembly on the human endothelial cell. AB - Through assembly of plasminogen and its activators, the endothelial cell surface may provide a favorable environment for constitutive generation of plasmin. This system may be regulated at multiple levels. Abundant expression of a 40-kDa protein with dual ligand-binding capacity may promote cell surface plasmin formation by colocalizing t-PA and plasminogen in a catalytically favorable configuration. Conversion of Glu-PLG to the preactivated form Lys-PLG, in the vicinity of the cell surface, may also precede plasmin formation. Physiologic concentrations of Lp(a), furthermore, may serve to modulate plasminogen activation at the cell surface by competing for binding sites, whereas elevated levels of Lp(a) might suppress this mechanism and lead to a subclinical prothrombotic state. Finally, cell surface binding sites for both plasmin and t PA appear to protect these molecules from their physiologic antagonists, alpha 2 plasmin inhibitor and plasminogen activator inhibitor, type-1, respectively. Plasmin formation may contribute to the nonthrombogenicity of the blood vessel wall. PMID- 8437980 TI - Cellular assimilation of water-soluble vitamins in the mammal: riboflavin, B6, biotin, and C. PMID- 8437981 TI - Characterization of 17 human immunodeficiency virus-1 carrier cell lines with T cell, myelomonocyte, or megakaryocyte lineages. AB - Of 29 hematopoietic cell lines tested for susceptibility to human immunodeficiency virus (HIV)-1HTLV-IIIB infection, all CD4+ cell lines became infected. Continuous culturing of infected cell lines resulted in nine HIV-1 carrier cell lines, including, for the first time, an HIV-1 carrier megakaryoblastic cell line, MEG-01/HIV. The immunophenotypic profiles of a total of 17 HIV-1 carrier cell lines (nine newly and eight previously established cell lines) were compared with their respective parental noninfected cell lines. Except for total absence of CD4 expression, the expression of other antigens was variable among the 17 HIV-1 carrier cell lines. Persistent and consistent replication of infectious HIV-1 was detected in all of them in varying quantities. The great variability observed in both the altered marker expression, with respect to that of the noninfected parental cell lines, and in the quantities of persistently produced infectious HIV-1 was, nevertheless, specific to the individual cell lines. Furthermore, the present study demonstrates that there is no apparent correlation in the quantity of HIV-1 produced to either T cell, myelomonocytic cell, or megakaryocytic cell types. Instead, the results suggest that a particular interaction between HIV-1 and individual clonal cell lines may provide insight into the extremely complex immune dysregulation associated with the pathogenesis of acquired immune deficiency syndrome. Thus, the 17 HIV-1 carrier cell lines of diverse origin presented here provide valuable and unique models for further understanding acquired immune deficiency syndrome pathogenesis at the cellular and molecular levels. PMID- 8437982 TI - Progesterone antagonist mifepristone (RU 486) decreases cardiotoxicity of cocaine. AB - RU 486, a potent progesterone antagonist, was used to determine whether RU 486 blocks the enhanced cardiotoxicity of cocaine mediated by progesterone upon rat papillary muscles. Groups of nonpregnant rats were pretreated with: progesterone for 3 days (n = 12); progesterone + RU 486 for 3 days (n = 12); progesterone for 3 days + single low dose RU 486, progesterone for 3 days + single high dose RU 486, and RU 486 for 3 days (n = 6); or were untreated (n = 12). Papillary muscles from these groups were electrically paced during exposure to cocaine concentrations ranging from 10(-14) M to 10(-3) M. One group (n = 6) was pretreated with RU 486, but not exposed to cocaine. The results showed that all muscles from rats pretreated with RU 486 for 3 days were functional when exposed to cocaine concentrations one to four orders of magnitude higher than tolerated by muscles from untreated or progesterone-treated rats. As indicated by alterations in contraction response patterns, RU 486 treatment for 3 days reversed progesterone-enhanced cardiotoxicity of cocaine. Single low dose and high dose RU 486 administrations also reversed progesterone's effects upon cocaine-induced cardiotoxicity. PMID- 8437983 TI - Effects of sex steroids on myocardial anoxic resistance. AB - Eight treatment groups of CD strain castrate male or female rats were injected daily with cottonseed oil (sham), testosterone propionate (50 micrograms/100 g body wt), estradiol benzoate (7 micrograms/100 g body wt), or a combination of both steroids dissolved in cottonseed oil. These physiologic replacement dosages of sex steroids, determined by bioassay procedures, were injected in a 0.1-ml bolus of cottonseed oil daily (intraperitoneally) for 16 weeks. Myocardial anoxic resistance was quantified by means of an in vitro right ventricular strip preparation that evaluated the ability of the isolated right ventricle to maintain contractions in response to electrical pacing at 1 Hz after 10 min of anoxia. While this parameter was elevated 2- to 3-fold in the estrogen-treated groups of male and female castrates compared with the sham (oil)-injected groups, neither testosterone treatment alone nor combination steroid treatment produced anoxic resistance values that differed significantly from those of the sham injected animals. Thus, although estrogen alone may afford anoxic protection to the myocardium, testosterone is able to abolish this hormone-induced protection. PMID- 8437984 TI - Selenium supplementation enhances the expression of interleukin 2 receptor subunits and internalization of interleukin 2. AB - Selenium (Se) is an essential nutritional factor that was shown previously by us to alter the kinetics of expression of high affinity (p55/p75) interleukin 2 receptors (IL-2R). This study shows that dietary (2 ppm for 8 weeks) or in vitro (1 x 10(-7) M) supplementation with Se (as sodium selenite) results in a significant upregulation of the expression of both the p55 and p70/75 IL-2 binding sites on the surface of concanavalin A-stimulated lymphocytes from C57BL/6J mice. This resulted in the formation of significantly higher numbers of high affinity IL-2R/cell with preservation of the normal ratio of high affinity to total IL-2 binding sites/cell. The high affinity IL-2R on cells from Se supplemented animals functioned normally in terms of ligand binding and kinetics of IL-2 internalization, but their greater numbers/cell resulted in the internalization of significantly larger amounts of IL-2/cell. As Se supplementation results in an earlier expression of greater numbers of high affinity IL-2R, the presence of Se in the cell environment can result in an accelerated clonal expansion of activated lymphocytes. PMID- 8437985 TI - Volume of renal cortical cytoplasm in rabbits, and basolateral transport gradients of cycloleucine and p-aminohippurate. AB - The intracellular volume of distribution of the nonmetabolizable sugar derivative 3-O-methylglucose was determined in the renal cortex of diuresing rabbits. This sugar is not well reabsorbed from the lumen, but is readily taken up across the basolateral cell membranes by an apparently flow-limited, nonconcentrative process. The ratio of distribution volumes of nonfiltered 3-O-methylglucose and inulin, therefore, equals the ratio of their mean artery-vein transit times. An intracellular and presumably cytoplasmic volume for 3-O-methylglucose of 0.13 ml/g was thus determined in the cortex of rabbits undergoing mannitol diuresis; similar values were obtained with three other less direct approaches. Availability of a reliable value permitted calculation of the activity gradients against which para-aminohippurate and the neutral amino acid cycloleucine can be accumulated at the basolateral membrane in vivo; both gradients equal about 6:1. This finding underlines the active nature of basolateral amino acid uptake and points to a further characteristic common to the organic anion and the cycloleucine carrier systems. PMID- 8437986 TI - Cyclosporin A-induced embryopathy in embryo culture is mediated through inhibition of the arachidonic acid pathway. AB - Embryos from Swiss Webster mice were grown in culture for 24 hr starting at Day 8.5 of gestation to study the effects of cyclosporin A (CsA) on the developing embryo. The embryos exposed to concentrations of CsA from 0.1 microgram/ml to 10.0 micrograms/ml developed a significant increase in the incidence of malformations from 28.6% to 78.6%, as compared with the 6.8% incidence of malformations in the control embryos. These malformations included defects in the neural tubes, head folds, and facial arches. In addition, inhibition of embryonic growth in CsA-exposed embryos was shown by a lower somite number, crown-rump length, and protein content than those of the control embryos. Supplementation of the culture medium with arachidonic acid or prostaglandin E2 decreased the incidence of CsA-induced malformations by 50% to 70% and prevented the CsA induced inhibition of growth. We conclude that CsA causes abnormal embryonic development in mouse embryo culture and that the mechanism of CsA-induced embryopathy involves inhibition of the arachidonic acid pathway. PMID- 8437987 TI - Role of gastric digestion in the absorption of slowly digestible peptide, oligo-L methionine, in rats. AB - Absorption of a slowly digestible peptide, oligo-L-methionine (OM), added to a low casein diet was faster than absorption of OM added to a low soybean protein isolate diet in early stages of feeding in chronic portal-cannulated rats. In the present study, the gastric digestion of 14C-labeled OM in rats fed a casein-based diet was higher than that in rats fed an soybean protein isolate-based diet 30 min and 3 hr after feeding. In rats with chronic bile-pancreatic juice diversion from the proximal small intestine, the higher gastric solubilization of OM in the stomach of the casein group was also observed, but the contents of soluble digest of OM in the stomach were lower than those in the normal rats. The portal absorption of OM in the casein group was higher than in the soybean protein isolate group both 30 min and 4 hr after feeding in the bile-pancreatic juice diverted rats, and the difference of the portal absorption between the diet groups corresponded to the difference of the amount of solubilized OM in the upper small intestine; this, in turn, depends on pepsin digestion in the stomach. These findings suggest that the difference between the two diet groups in the ability to digest OM in the stomach can at least partly explain the higher portal absorption of OM in the casein group in the early stages of feeding. PMID- 8437988 TI - Effect of alcohol, neurohypophysectomy, and vasopressin antagonists on hemorrhage induced bradycardia in the rat. AB - During initial stages of hemorrhage in the rat, cardiovascular compensation leads to a tachycardia (mean +/- SE, 5.2 +/- 0.7%; n = 23) that helps prevent a large fall in blood pressure. This compensatory phase is followed by a decompensatory phase in which mean arterial pressure and heart rate fall. A rise in arginine vasopressin (AVP) levels has been postulated as the cause of this hemorrhage induced bradycardia (HIB). The object of the present study was to determine whether interference with AVP release by alcohol anesthesia or neurohypophysectomy or by blockade of AVP receptors in the plasma or cerebral spinal fluid could attenuate HIB. Male Wistar rats were anesthetized with pentobarbital, surgically prepared, and bled to maintain a blood pressure of 40 50 mm Hg. After hemorrhage, heart rate decreased 15 +/- 2% (n = 6) with alcohol anesthesia compared with 32 +/- 3% (n = 7) with pentobarbital. After neurohypophysectomy, however, HIB remained unchanged (-15 +/- 2%; n = 5) compared with sham-operated controls (-19 +/- 3%; n = 6). Peripheral administration of two nonselective V1/V2 antagonists and one V2 antagonist had no effect on HIB, whereas a V1 antagonist significantly attenuated the heart rate decrease (-15 +/- 4%; n = 6) compared with controls (-32 +/- 3%; n = 7). None of the AVP antagonists tested at one tenth the peripheral dose had any effect on HIB when administered into the lateral ventricle of the brain, although a mixed serotonin, dopamine, and catecholamine antagonist, spiperone, potentiated the response. It was concluded that although peripheral release of AVP may be partially involved in the heart rate response to hemorrhage, central AVP release and central AVP receptors were not involved in HIB. PMID- 8437989 TI - Hormonal and electrolyte responses to acute isohemic volume expansion in unanesthetized rats. AB - This study was undertaken to explore the time course of the metabolic response to isohemic blood volume expansion (30%) in normotensive, unanesthetized Sprague Dawley rats. Whole blood, drawn from a femoral artery catheter of conscious donor rats, was infused into the jugular vein of recipient rats. Blood samples were drawn from a carotid artery of recipient rats at time points beginning immediately post-volume expansion (IPVE) up through 5 days post-volume expansion (PVE). To characterize the attendant compensatory mechanisms, the plasma concentrations of electrolytes and fluid regulatory hormones were determined. Hematocrit began to raise IPVE and was significantly elevated above control IPVE 20, 30, 40, 60, and 90 min, and 2, 4, 6, 8, 12, and 24 hr PVE. Consistent with our current understanding of the hormonal response to excess volume, atrial natriuretic factor was significantly increased above the prevolume expansion (control) values 0-30 min PVE. Surprisingly, plasma aldosterone levels were significantly increased above control at 20 and 30 min and 6 hr PVE, whereas plasma renin activity was significantly decreased 30-40 min PVE. Plasma sodium was not changed from control values except for a significant increase at 6 hr post-volume expansion. Plasma potassium, osmolality, and arginine vasopressin levels were not altered by the volume expansion. These studies delineate the physiologic time scheme operative in the regulation of fluid volume during acute ischemic volume expansion. PMID- 8437990 TI - Effect of dietary carbohydrate and phenotype on sucrase, maltase, lactase, and alkaline phosphatase specific activity in SHR/N-cp rat. AB - The obese spontaneous hypertensive rat/NIH-corpulent (SHR/N-cp) rat exhibits some of the metabolic and pathologic alterations associated with non-insulin-dependent diabetes mellitus and hypertension. The current study was conducted to investigate the influence of phenotype (ob versus In) and source of dietary carbohydrate (sucrose versus starch) on intestinal sucrase, maltase, lactase, and alkaline phosphatase activity in SHR/N-cp rats. For 3 months, lean and obese male SHR/N-cp rats were fed isocaloric diets containing as the sole source of carbohydrate either 54% cooked corn starch or sucrose. Serum and urine markers for diabetes were observed in obese rats. Wet weight and length of intestines were significantly increased in obese rats compared with lean littermates. Among the intestinal enzymes measured, statistical tests confirmed that sucrase activity was significantly increased (P < 0.01) by both phenotype (ob > In) and feeding a sucrose diet. Diet alone (sucrose > starch) significantly increased (P < 0.05) maltase activity in obese rats, but had no effect on lean rats. Lactase activity was significantly higher (P < 0.05) in obese sucrose-fed rats compared with obese starch-fed and/or lean littermates. Statistical tests revealed that intestinal alkaline phosphatase activity was significantly altered (P < 0.05) by both phenotype and diet. Intestinal alkaline phosphatase was higher in starch-fed lean rats compared with lean littermates fed sucrose and to starch or sucrose-fed obese rats. These results are not indicative of a simple, nonspecific increase in intestinal enzyme activity, since the effects observed in intestinal alkaline phosphatase contrast the effects observed in intestinal sucrase, maltase, and lactase activity. These results indicate that both phenotype and diet alter structural and enzymatic intestinal activities of SHR/N-cp rats. Distinct variations in the observed intestinal enzymatic activities suggest that these enzymes are under the control of genetic, hormonal, and dietary factors. Rationale for these differences are discussed. PMID- 8437991 TI - Glucocorticoid-prolactin interactions in Nb2 lymphoma cells: antiproliferative versus anticytolytic effects. AB - The interaction between the immunosuppressive effects of glucocorticoids and the mitogenic effects of prolactin (PRL) were examined in Nb2 lymphoma cells, a pre-T cell line. The synthetic glucocorticoid, dexamethasone (Dex), caused a concentration-dependent (6.25-200 nM) inhibition of basal and ovine PRL (oPRL) stimulated Nb2 cell proliferation. Although Dex was antiproliferative, the steroid had no effect on cell viability in the presence of PRL. However, when PRL was omitted from the medium, Dex increased the proportion of dead Nb2 cells by 24 hr in a concentration (25-200 nM)-dependent fashion without affecting total cell number. The antiproliferative and cytolytic effects of Dex were mimicked by other corticosteroids (cortisol, corticosterone, aldosterone, and deoxycorticosterone) in the expected order of glucocorticoid potency, but not by other steroids (17 beta-estradiol, progesterone, testosterone, 5-alpha-dihydrotestosterone, and dehydroepiandrosterone) or triiodothyronine. In addition, the antiproliferative and cytolytic effects of glucocorticoids were antagonized by the glucocorticoid receptor antagonist RU 486. Since corticosteroid-induced cytolysis was apparent only in the absence of mitogen, the anticytolytic effects of oPRL were tested. In the presence of Dex (100 nM), oPRL (25-1600 pg/ml) caused a concentration dependent inhibition of cytolysis without changing cell number. Other lactogenic hormones (human growth hormone, human placental lactogen, rat PRL), but not trophic nonlactogenic hormones (rat growth hormone, human chorionic gonadotropin, ACTH), also inhibited Dex (100 nM)-induced cytolysis. Agarose gel electrophoresis of DNA extracted from Nb2 cells revealed that within 12 hr, 100 nM Dex induced DNA fragmentation, indicative of programmed cell death or apoptosis. Coincubation of cells with Dex and oPRL (1 ng/ml) inhibited Dex-induced fragmentation of Nb2 cell genomic DNA. These studies reveal a complex interaction between glucocorticoids and PRL in Nb2 cells. Although a glucocorticoid receptor-mediated antiproliferative effect is evident, PRL (at concentrations that usually stimulate cell proliferation) has the capacity to protect the cell against glucocorticoid-receptor-mediated induction of apoptosis. PMID- 8437992 TI - Differences in the plasma transport and tissue concentrations of tocopherols and tocotrienols: observations in humans and hamsters. AB - Certain aspects of tocopherol and tocotrienol absorption, plasma transport, and tissue distribution were examined in humans and hamsters. Plasma transport differed in that tocopherols were found primarily in low density lipoprotein and high density lipoprotein in association with plasma surface components, whereas tocotrienols disappeared from plasma with chylomicron clearance. In keeping with transport by triglyceride-rich lipoproteins, tocotrienols were deposited in conjunction with triglycerides in the adipose tissue of hamsters. In hamsters, tocopherols were the only tocol readily detected in all tissues, except adipose during tocotrienol supplementation. In fasting humans, the plasma tocotrienol concentration was not significantly increased after tocotrienol supplementation, whereas the platelet concentration of delta-tocotrienol doubled. Furthermore, tocotrienol intake did not appear to modulate the plasma cholesterol concentration in normolipemic hamsters. Thus, the transport, tissue concentration, and relative biologic function of tocopherol and tocotrienol appear somewhat disparate and possibly unrelated. PMID- 8437993 TI - Gastrin-mediated changes in tyrosine kinases in isolated gastric mucosal cells from young and aged rats. AB - The present investigation examines the changes in tyrosine kinase (Tyr-k) activity and tyrosine-specific phosphorylation of membrane protein(s) in isolated gastric mucosal cells from young (3 months) and aged (22 months) Fischer-344 rats after exposure to gastrin. In mucosal cells from young rats, a 15-min time course study revealed a steady rise of Tyr-k activity for the first 2 min in response to 10(-9) M gastrin (G-17 I), whereafter the enzyme activity decreased sharply. In these cells, a significant 90% (P < 0.001) increase in the enzyme activity was observed only after 30 sec of exposure to gastrin, with maximal stimulation (124%; P < 0.001) occurring after 2 min. These increases were also associated with a 2- to 3-fold rise in tyrosine-specific phosphorylation of 55-, 80-, and 100-kDa membrane proteins. In contrast, in mucosal cells from aged rats, neither Tyr-k activity nor tyrosine phosphorylation of membrane proteins was affected by gastrin with doses up to 10(-6) M. Our observation of an immediate induction of Tyr-k activity and tyrosine phosphorylation of certain membrane proteins by gastrin in gastric mucosal cells from young, but not from aged, rats suggests that these events may play an important role regulating some of the physiologic actions of gastrin at different stages of life. PMID- 8437994 TI - Blunting effect of pepsanurin introduced in the duodenum on the atrial natriuretic peptide diuretic action in rats. AB - Pepsanurin (PU) is a peptide(s) obtained by pepsin hydrolysis of human plasma or its globulin fraction. We have reported that the accelerated renal excretory rate induced by atrial natriuretic peptide (ANP) can be considerably blunted by PU either in the intact rat or in the isolated perfused rat kidney. We explored whether or not PU can be part of a signaling mechanism originated in the digestive tract, involved in the regulation of water and electrolyte homeostasis. PU obtained either from human (0.5 ml) or rat plasma (0.25-0.5 ml) administered into the duodenal lumen of rats, counteracted significantly the diuretic saluretic action of a 0.5- microgram bolus of ANP, reproducing qualitatively the effect of its intraperitoneal administration. Human PU reduced the ANP-stimulated renal excretion by 67-90% for Na (P < 0.001) and by 35-54% for water (P < 0.02-P < 0.001); the inhibition induced by rat PU was 45-96% for Na (P < 0.05-P < 0.01) and 35-65% for water (P < 0.05-P < 0.01). Rat PU (0.5 ml) abolished the rise of glomerular filtration rate induced by ANP without affecting fractional Na excretion. All the samples tested decreased K excretion, but in some experiments, the difference did not reach statistical significance. Contrary to the effect of PU, the introduction in the duodenum of (i) isotonic glucose solution, (ii) hydrolysate of bovine serum albumin, or (iii) hydrolysate of casein prepared after the same procedure yielding PU from plasma failed to produce an inhibition of the ANP stimulation of renal excretory rate. In addition, human plasma incubated at 37 degrees C for 24 to 48 hr, prior to pepsin digestion, did not yield PU, which indicates that PU is generated from a substrate sensitive to endogenous enzymes and/or that its stability is vulnerable to endogenous enzymes. PMID- 8437995 TI - Pseudomonas aeruginosa exotoxin A enhances automaticity and potentiates hypoxic depression of isolated rat hearts. AB - The potent virulence factor exotoxin A, produced by Pseudomonas aeruginosa, has been reported to suppress the synthesis of the alpha-subunit of cardiac Gi protein and may have general effects upon synthesis of other myocardial proteins. To determine whether such exotoxin A actions influence specific functional properties of the intact heart, characteristics of isolated perfused hearts obtained from rats receiving injections of exotoxin A 48 hr before sacrifice were compared with those of rats receiving no exotoxin A. Exotoxin A treatment increased the spontaneous beating rates and potentiated the suppressive effects of hypoxia upon heart rate, left ventricular systolic pressure, and rates of ventricular contraction and relaxation. On the other hand, exotoxin A treatment did not influence the magnitude or rate of pressure development under control conditions, the positive chronotropic and inotropic responses to isoproterenol, or the negative chronotropic responses to adenosine. Since a specific exotoxin A induced suppression of myocardial alpha-subunit of the Gi protein should confer hypersensitivity to isoproterenol and reduced sensitivity to adenosine, the absence of alterations in responses to these interventions suggests that exotoxin A's effect was not confined to specific suppression of this protein. However, net effects of exotoxin A exposure included a pronounced increase in excitability of the hearts and enhanced vulnerability to hypoxic insults. PMID- 8437996 TI - Miniature isotropic optical fibre probes for quantitative light dosimetry in tissue. AB - A small detector to measure light fluence rates in turbid media and biological tissue, based on an optical fibre with a fluorescent dye-doped tip, is presented. The measured optical power of the fluorescent light transmitted through the fibre is directly proportional to the local fluence rate of the treatment or excitation light at the tip. The detector has been built as small as 170 microns outer diameter, while retaining good mechanical properties for insertion into soft tissue. The detector response is linear with fluence rate over a wide range and isotropic for all angles less than 160 degrees from the forward direction. Hence, the detector can measure accurately the fluence rate in turbid media and biological tissue. This fluorescent tip design has no fundamental restrictions in size and shows comparable isotropy, but is less sensitive than, fluence rate detectors based on optical fibres with light-scattering tips. PMID- 8437997 TI - A computerized autofluorescence and diffuse reflectance spectroanalyser system for in vivo skin studies. AB - A microcomputer-controlled spectroanalyser system has been set up to study optical properties of normal and abnormal human skin in vivo. The system can measure both tissue autofluorescence and diffuse reflectance at selected skin locations. The sample holder allows adjustment of the incident angle of the illumination light and the pick-up angle of the collected light providing the means to examine different depths of skin tissue. Using this system, we detected measurable skin autofluorescence with a maximum at about 470 nm when excited with 380 nm UV radiation. In this work, we also show that the absorption and scattering properties of the skin tissue (which can be determined from the measured diffuse reflectance spectrum) affect the shape of the autofluorescence spectrum. We believe that the combination of autofluorescence and diffuse reflectance measurements will lead to better understanding of the optical properties of normal and abnormal skin tissue. PMID- 8437998 TI - Direct cone beam SPECT reconstruction with camera tilt. AB - A filtered backprojection (FBP) algorithm is derived to perform cone beam (CB) single-photon emission computed tomography (SPECT) reconstruction with camera tilt using circular orbits. This algorithm reconstructs the tilted angle CB projection data directly by incorporating the tilt angle into it. When the tilt angle becomes zero, this algorithm reduces to that of Feldkamp. Experimentally acquired phantom studies using both a two-point source and the three-dimensional Hoffman brain phantom have been performed. The transaxial tilted cone beam brain images and profiles obtained using the new algorithm are compared with those without camera tilt. For those slices which have approximately the same distance from the detector in both tilt and non-tilt set-ups, the two transaxial reconstructions have similar profiles. The two-point source images reconstructed from this new algorithm and the tilted cone beam brain images are also compared with those reconstructed from the existing tilted cone beam algorithm which requires rebinning the projection data. These comparisons demonstrate that the new algorithm, compared with the existing tilted cone beam algorithm, can provide better image contrast and improved image resolution. PMID- 8437999 TI - Optimization of beam orientations in radiation therapy: some theoretical considerations. AB - The problem of optimizing beam orientations for irradiations with multiple fixed beams is investigated. It is shown that this is a complex, in mathematical terms 'non-convex', optimization problem, whose solution requires sophisticated techniques. In this work, the optimization is performed with the method of simulated annealing. In order to keep the calculation time within reasonable limits, the problem is expressed in the spatial frequency domain using Parseval's theorem. All calculations are then performed in the frequency domain. The algorithm is described in detail. Various treatment techniques, including intensity modulation, are considered. The results for various exemplary cases are presented. They are based on a simplified dose calculation model. A general conclusion is that the optimum beam configuration for multiple-beam irradiations (with more than three beams) tends to be an even distribution over an angular range of 0 to 2 pi. PMID- 8438000 TI - An image processing technique for the identification of contact pixels applied to x-ray CT images of implanted hip prostheses. AB - Uncemented prosthetic joint implants used in orthopaedic surgery are usually coated with a porous surface to encourage bone ingrowth. Better contact between the endosteal bone and the porous surface improves ingrowth, and such contact may be increased if the joint further subsides into position in the first weeks following implantation. An image processing technique has been developed as part of a study undertaken to determine the effect of early subsidence on endosteal contact. The method provides a measure of the degree of contact between the surfaces from transverse x-ray CT images, but is suitable for application to any image with a similar intensity distribution. PMID- 8438001 TI - Riyadh on my mind. PMID- 8438002 TI - Diagnostic classification of patients with low back pain: report on a survey of physical therapy experts. AB - BACKGROUND AND PURPOSE: A survey of expert orthopedic physical therapists was conducted to assist in the development of a classification system for patients with low back pain (LBP). The goal of the survey was to measure levels of agreement on labels and accompanying constellations of signs and symptoms for subgroups of patients with LBP. SUBJECTS: Twenty-four of the 30 expert orthopedic physical therapists who were originally contacted responded to the survey request. METHODS: A modified Delphi technique was used. The first stage involved a review of the literature and identification of 25 diagnostic classes of LBP. Experts were asked to rate the "appropriateness" of each diagnostic class for inclusion in a classification scheme. Clinical findings relevant to each diagnostic class were identified and rated on the degree of "essentialness" to that class. RESULTS: Three diagnostic classes--hypomobility dysfunction, nerve root adhesion, and sacroiliac hypermobility--were distinct in that the agreement criteria for the appropriateness of diagnostic classes as well as the surveyed essential signs and symptoms were met. Six of the 25 diagnostic classes did not meet the minimum levels required for agreement as appropriate diagnostic classes: facet syndrome, chronic pain behavior, muscle strain, iliolumbar ligament sprain, posterior ligament sprain, and myofascial dysfunction. CONCLUSION AND DISCUSSION: The importance of developing homogeneous subgroups of patients with LBP based on constellations of reliable clinical findings is emphasized. PMID- 8438003 TI - The effects of an AIDS education program on the knowledge and attitudes of a physical therapy class. AB - BACKGROUND AND PURPOSE: The purpose of this investigation was to determine the effect of an education unit on physical therapy students' knowledge about acquired immunodeficiency syndrome (AIDS), their attitudes toward patients with AIDS, and their willingness to treat patients who have AIDS. SUBJECTS: A sample of convenience of 103 entry-level undergraduate junior physical therapy students, aged 20 to 35 years (mean = 22.1, SD = 2.8), from one class at one institution participated in this study. METHODS: A two-group pretest-posttest with control group delayed-intervention design was used. Subjects were randomly assigned to either a group that received an AIDS education unit (experimental group) or a group that did not receive a special education unit (control group). All subjects were pretested and posttested together with a modified version of the State University of New York at Buffalo School of Nursing AIDS Study Questionnaire. Willingness to treat patients who have AIDS was assessed based on self-report responses. After the pretest of both groups, the experimental group received an AIDS education unit followed by the posttest, whereas the control group received no AIDS education unit before the posttest. RESULTS: The experimental group showed significant improvement of knowledge, attitudes, and willingness to treat patients who have AIDS as a result of the AIDS education unit. The control group showed no significant change or a lowered score and thus a change in a nondesired direction. The results of this study confirm the effectiveness of an AIDS education program for physical therapy students at this institution. CONCLUSION AND DISCUSSION: Further study of entry-level graduate physical therapy students, licensed physical therapists, and other allied health professionals is needed to determine whether the education of these groups can affect their knowledge and attitudes toward patients with AIDS. Improved knowledge and attitudes of the health care provider with an increased willingness to treat patients who have AIDS ensures these patients will receive optimal and appropriate health care. PMID- 8438004 TI - Vacuum-compression therapy for the treatment of an ischemic ulcer. AB - This case report describes the use of a new medical device that utilizes vacuum compression therapy (VCT) in the management of a 30-year-old female patient with severe arteriosclerosis and an associated nonhealing fasciotomy wound. Attempts were made to treat the patient with local care consisting of debridement and saline-moistened gauze dressings. Following a poor response to nonsurgical management, a skin graft was performed in an attempt to encourage more rapid healing. Infection and poor healing followed the graph, and only 40% of the graft remained viable after 12 days. Outpatient physical therapy management consisted of hydrotherapy and hydrocolloid dressings. This treatment resulted in minimal success until combined with VCT. The patient received hydrotherapy, VCT, and hydrocolloid dressings three times per week for 11 weeks. Wound healing occurred at an average rate of 0.64 cm2 per day, and the wound completely reepithelialized by the end of the eighth week of VCT therapy. Increased capillary filling is proposed as a primary factor in the improved healing. PMID- 8438005 TI - A longitudinal study of children with Down syndrome who experienced early intervention programming. AB - BACKGROUND AND PURPOSE: The long-term motor, cognitive, and adaptive functioning of a sample of adolescents with Down syndrome who experienced an early intervention program was examined in this descriptive study. SUBJECTS: Ten children with Down syndrome (7 girls, 3 boys) who had participated in an early intervention program constituted the early intervention (EI) group. An age matched group of children with Down syndrome (6 girls, 4 boys) who had not experienced an early intervention program served as a comparison group. METHODS: The EI group's motor functioning was compared with that of a normative sample used in the development of the Bruininks-Oseretsky Test of Motor Proficiency. The cognitive and adaptive skills of the EI group were compared with those of the comparison group. The children were assessed using the Stanford-Binet Intelligence Scale, the Vineland Social Maturity Scale, and the Bruininks Oseretsky Test of Motor Proficiency. RESULTS: The EI group subjects fell below their chronological age levels in gross and fine motor skills; however, their mean gross motor skill levels exceeded their mean fine motor skill levels. The specific deficits in gross motor and fine motor skills, which were documented in a previous follow-up study on the same sample, continued to be areas of deficits (visual motor coordination, running speed, balance, and reaction time). The EI group subjects had significantly higher scores on measures of intellectual and adaptive functioning than did the children in the comparison group. The EI group subjects did not show the decline typically seen with age in adaptive functioning in individuals with Down syndrome. CONCLUSION AND DISCUSSION: Because of the design limitations, the differences between the groups should be interpreted with caution. PMID- 8438006 TI - Movement patterns of adolescents rising from a bed. AB - BACKGROUND AND PURPOSE: The purposes of this study were to describe the movement patterns (MPs) adolescents use when rising from a supine position on a bed to a standing position and to determine whether these MPs vary with age across adolescence. SUBJECTS: Sixty nondisabled adolescents participated in the study. METHODS: Twenty adolescents from each of three age groups (ie, 11, 14, and 17 years) were videotaped performing 10 trials of rising from a bed. The MPs of each of four body regions were described, and the most common forms of movement observed in each age group were determined. RESULTS: The observed incidence (frequency of occurrence) of MPs in each body region varied with age, and in two of the four regions, the predominant pattern varied across age groups. Eighty nine different forms of rising were observed, with the greatest variability among 11-year-old subjects. The most frequent forms of rising were seen in only 5% to 15% of the trials for each age group; one of these was common across age groups. CONCLUSION AND DISCUSSION: Therapists should consider how MPs vary with age and avoid unnecessarily using a specific approach when teaching this activity. PMID- 8438007 TI - Implications of elbow arthrodesis for individuals with paraplegia. AB - A 38-year-old woman who had a recent injury resulting in T-3 Frankel Class C paraplegia and a comminuted fracture of the right elbow is described in this case report. The elbow required an arthrodesis, but the position in which the elbow should be fused was not initially known. To illustrate to the rehabilitation team and the patient the advantages and disadvantages of each of two elbow positions under consideration for the arthrodesis, the author recruited an individual with paraplegia to demonstrate some activities of daily living with two elbow splints that stimulated the two positions of fusion being considered. The patient and the rehabilitation team concluded that the 30-degree flexion fusion offered more functional mobility than the 90-degree flexion fusion. At the completion of her initial rehabilitation, the patient was a full-time manual wheelchair user. She was independent in all self-care and transfers, including uneven transfers to heights of 22.9 cm (9 in) over and 45.7 (18 in) lower than the wheelchair seat. She drives a four-wheel-drive vehicle and is independent in stowing her wheelchair. PMID- 8438008 TI - Expansion-augmentation of the breast. AB - Patient expectations for superlative results with breast augmentation are higher than ever, challenging the surgeon to interpret the patient's desired final breast size correctly and create natural-appearing breasts. One method that gives an aesthetically pleasing result and allows for patient input in determining breast size is the use of overexpansion with the Becker expandable prosthesis. This study shows the results of overexpansion-augmentation in 23 women, all of whom received smooth or textured Becker expandable implants. The procedure involved inflating the prostheses gradually at regular intervals after the initial surgery. When the patient indicated the size she preferred, the implants were inflated with an additional 150 to 200 cc for 4 weeks, at which time the excess was removed. This 4-week overexpansion period results in a natural shaping of the breast and gives patients control over the final size. PMID- 8438009 TI - Breast capsular contracture: a retrospective study of textured versus smooth silicone implants. AB - Recent media attention has transformed breast augmentation, a routine surgical procedure, into a highly controversial one. Capsular contracture is cited in both the lay press and scientific literature as the most frequent complication of breast augmentation. This retrospective study compares two similar groups of breast augmentation patients. The first group consists of 98 consecutive patients utilizing smooth-surface silicone implants, and the second group consists of 99 consecutive augmentations using textured-surface silicone implants. The operative technique and postoperative care were identical--with the surface differences being the only significant variable. Textured-surface silicone implants are shown statistically to reduce capsular contracture to 4 percent, compared with a 21 percent incidence with smooth-surface silicone implants. PMID- 8438010 TI - Combined tissue expansion: clinical attempt to decrease pain and shorten placement time. AB - Tissue expansion can be characterized as a unique reconstructive procedure that takes advantage of the intrinsic ability of tissues to stretch and, in some instances, to grow in response to expansive forces. The efficacy of combined intraoperative expansion to obtain sufficient expanded tissue more rapidly was tested in reconstructions of the extremities, and the comparison between conventional and combined expansion was performed observing five parameters: initial injected volume, pain score, duration of pain, total period of expansion, and histologic findings. We treated 22 patients with conventional expansion and 29 with combined expansions. The latter approach enabled us to overexpand the expanders initially and was associated with lower pain scores than conventional expansion. Furthermore, in the combined expansion group, shortening of the duration of pain was statistically significant in the upper arm (p < 0.05) as well as in the lower leg (p < 0.01). In this group, the total expansion period also was significantly shorter (p < 0.01). Histologically, only minor differences were seen between groups. In this study, intraoperative expansion combined with subsequent rapid overinflated expansion proved to be superior to conventional expansion not only in reducing expansion time but also in decreasing pain. We consider the following effects to contribute to this result: (1) increased skin elasticity due to repeated intraoperative load cycling, which leads to easier expansion of the skin and less irritation of the sensory nerves, (2) improved survival and vascularization of skin flaps due to the "delayed-flap" phenomenon, and (3) prevention of shrinkage of the expanded skin and widening of scars due to overinflated expansion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8438011 TI - Enophthalmos following orbital transposition for craniofacial malformations. AB - This is a retrospective study of the frequency and factors that portend enophthalmos following orbital osteotomies and transposition for craniofacial malformations. Clinically obvious postoperative enophthalmos (POE) was noted in 23 (37.7 percent) of 61 patients undergoing such procedures. Postoperative enophthalmos was observed in 86 percent of Apert patients who had combined anteromedial orbital transposition and in 48 percent of patients with hypertelorbitism who had standard 360-degree osteotomies. In contrast, the incidence of postoperative enophthalmos was 21 percent following frontofacial (monobloc) or subcranial (Le Fort III) advancement. Postoperative enophthalmos also correlated with the occurrence of orbital fracture/fragmentation and with disruption of the periorbita. This study underscores the importance of establishing the correct relationship of the globe to the orbital rim (euophthalmos) while maintaining the spatial position of the eye, especially its anterior projection. Postoperative enophthalmos can be prevented by inserting bone grafts into orbital osteotomy gaps, correcting orbital volume/morphology following floor or wall outfracture/fragmentation, and preserving the periorbital supporting system. PMID- 8438012 TI - Postoperative care after craniofacial surgery: evaluation of routine laboratory testing. AB - In this study, two protocols for monitoring children after major craniofacial surgery were compared. The first protocol consisted of repetitive laboratory testing in 37 children to detect surgical and medical complications during a 2 year period. None of the complications were predicted by abnormal test results, and abnormal results of routinely performed tests never led to a change in management. The second protocol, an adapted version of the first protocol, was continued for 5 years as a prospective study in 98 children: Patients were routinely tested only once, and further testing was initiated either after an abnormal test result or because of clinical symptoms. Clinical management and the incidence of postoperative complications did not differ between groups. The second protocol considerably reduced the mean number of tests per patient from 42.5 to 7.0, but in contrast with the first protocol, 84 percent of abnormal test results led to changes in clinical management. In conclusion, in the first group the test results were not used and were not predictive of complications. In the second group, tests were more apt to have abnormal results and often initiated treatment. This shows that indiscriminate routine laboratory testing is of limited value in covering the postoperative period after craniofacial surgery. PMID- 8438013 TI - Use of a free conchal cartilage graft for closure of a palatal fistula: an experimental study and clinical application. AB - In order to establish an operative procedure for the closure of palatal fistulas, the usefulness of free conchal cartilage grafts was confirmed through animal experiments, and a clinical application of this procedure was attempted. In the animal experiment, an oronasal penetrating fistula 10 mm in diameter was formed in the hard palate of 33 rabbits. One month later, the size of the palatal fistula decreased to 2 to 3 mm in diameter in all the rabbits. These rabbits were divided into two groups. Group 1 (n = 8) was used as a control group. In group 2 (n = 25), the palatal fistula was closed by an autograft of conchal cartilage, and the conchal cartilage graft site was observed for a period of 16 weeks. In 75 percent (6 of 8) of group 1, the palatal fistula persisted even after 1 year, but in 96 percent (24 of 25) of group 2, the palatal fistula was closed. The palatal fistula closure procedure using a conchal cartilage graft was found to be remarkably effective (chi 2c = 10.9, p < 0.001). In the clinical application, a fistula closure procedure with the use of conchal cartilage grafts was attempted in 24 patients with palatal fistulas. The procedure was modified into three types according to the size of the palatal fistula. For type I (diameter less than 2 mm) a conchal cartilage graft was created as in the animal experiment. For type II (2 to 5 mm in diameter), a palatal fistula closure procedure was used employing both a small hinge flap and a conchal cartilage graft.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8438014 TI - Intraoperative rapid expansion in cleft palate repair. AB - Intraoperative rapid expansion in cleft palate repair increases surface area by distension of the palate and recruitment of the surrounding palate tissue. A 5-cc Foley catheter with the distal tip trimmed is employed as the tissue expander. Intraoperative rapid palate expansion is proposed for closure with less tension of large gaps between cleft borders. This procedure has not demonstrated any deleterious clinical effects in cleft palate repair. PMID- 8438015 TI - Lip parameters in Nigerian children. AB - This is a study of lip dimensions in normal Nigerian children. It was carried out at University College Hospital, Ibadan, Nigeria, between January of 1986 and January of 1987. Two hundred and forty children of both sexes and aged from birth to 12 years had parameters relating to the anatomy of the human lip evaluated. The parameters determined included length of the upper vermilion arc, width of the mouth, and heights of the cutaneous upper lip and upper vermilion. All measurements were taken with the lips at rest. The length of upper vermilion arc and mouth width demonstrated a steady increase with age, mean male values being significantly greater than female values at 2 to 3 and 8 to 9 years. The heights of the cutaneous upper lip and upper vermilion showed an initial steady growth up to 6 years, followed by a decline in the rate of growth of the lip. There was a linear relationship between weight and height of the children and upper vermilion arc length, mouth width, and height of the cutaneous upper lip. Objective assessment of the size of the lip and mouth and surgical planning based on established standards are recommended. PMID- 8438016 TI - Repeated skin expansion for excision of congenital giant nevi in infancy and childhood. AB - Three children with giant pigmented nevi were treated by repeated tissue expansion. Five flaps were expanded twice, and one flap was expanded three times. The delay between expansions was 4 to 15 months (mean 9 months). With full inflation, vascularization of the flap remained good. However, every new expansion decreased flap length by 50 percent. Overall results with this technique, especially in two infants with giant pigmented nevi involving respectively 20 and 40 percent of the body surface, have been most impressive. Only one major complication has occurred: erosion of the skin caused by a fold of the expander envelope resulting in exposure of the expander. This technique improves the early surgical management of giant pigmented nevi and may provide better long-term functional and cosmetic results. PMID- 8438017 TI - Lateral canthal tendon resection with conjunctiva preservation for the treatment of lower eyelid laxity during lower eyelid blepharoplasty. AB - Lower eyelid laxity is a problem commonly encountered in patients undergoing lower eyelid blepharoplasty. Two problems associated with the numerous surgical procedures used for the management of this condition are (1) postoperative alteration of the shape of the palpebral fissure and lateral canthal angle and (2) difficulty with appropriate suture positioning or placement when reattaching the resected lateral canthal tendon. To address these problems, the surgical technique of lateral canthal tendon resection was modified by preserving the lateral conjunctiva, thus maintaining normal anatomic landmarks and ensuring proper suture placement. To date, this technique has been performed effectively on 50 patients who demonstrated mild to moderate eyelid laxity during preoperative evaluation for lower eyelid blepharoplasty. The only complication encountered has been undercorrection in one patient. The benefits of this procedure have been prevention of alteration of the palpebral fissure or canthal angle shape, greater ease and more accurate suture placement when reattaching the lateral canthal tendon, and avoidance of the need for full-thickness eyelid resection. PMID- 8438018 TI - Lifting the malar fat pad for correction of prominent nasolabial folds. AB - The anatomic presence of a discrete malar fat pad has not been widely recognized. In his paper on the "deep plane rhytidectomy," Hamra describes the increased thickness of the subcutaneous fat over the anterior midface. Cadaver and clinical studies confirm the consistent presence of a localized subcutaneous malar fat pad overlying the body of the zygoma and maxilla. Downward displacement of the infraorbital skin and underlying malar fat pad causes an increased prominence of the nasolabial fold. The surgical dissection of the malar fat pad starts from the malar eminence at the plane of the orbicularis oculi muscle and superficial to the origin of the zygomaticus and levator muscles, which are invested by the SMAS. There is an easily dissected plane deep to the fat pad that extends to the nasolabial crease. Surgical correction of the prominent nasolabial fold is enhanced by undermining the malar fat pad and advancing it laterally by traction on the skin flap with additional upward fixation by sutures between the lateral edge of the fat pad and the subcutaneous fascia at the lateral malar eminence. PMID- 8438019 TI - The middorsal notch: an intraoperative guide to overresection in secondary rhinoplasty. AB - A notch commonly appears at the midpoint of the nasal dorsum when the bridge has been resected beyond the ability of the soft tissues to contract. This notch, commonly seen in secondary rhinoplasty patients, occurs at the cephalic end of the supratip convexity and appears whether or not the tip has been overresected. The notch corresponds to the center of the "inverted V" deformity that signals middle vault collapse and may occur even when the middle vault has been reconstructed by spreader grafts. The middorsal notch also appears intraoperatively and therefore can guide the surgeon in determining the limits of dorsal skeletal resection. Ablation of the mid-dorsal notch by dorsal grafting is effective in both primary and secondary rhinoplasty patients. PMID- 8438020 TI - Ischemia tolerance of free-muscle flaps: an NMR-spectroscopic study in the rat. AB - The ischemia tolerance of free-muscle flaps was investigated in the rat by orthotopic and syngeneic transplantation of muscle flaps measuring 4 x 2.5 cm. The effects of ischemia with a maximal duration of 7 hours on the raised flaps and of anoxia caused by occlusion of the flap vessels were studied for the first time using 31P-spectroscopy. Energy metabolism was found to recover fast after 3 hours of ischemia, whereas a duration of 4 hours led to severe, only slowly reversible changes. Longer periods of ischemia resulted in a complete loss of energy reserves (PCr) and weaker ATP signal. The complete absence of ATP and a pH value under 6 indicated irreversible muscular damage. PMID- 8438021 TI - Vascularized tail bone grafts in rats. AB - A new experimental model for vascularized corticocancellous bone grafts was established by investigation of vascular anatomy of the tail in 15 adult Fischer 344 rats and determination of the viability of vascularized tail bone grafts into the abdominal wall in 22 7-week-old rats. The tail bones of 40 rats were then raised on the pedicle of the caudal artery and its venae comitantes, transferred to a resected portion in the femur, and observed for 16 weeks. The vascularized graft showed marked reactive periosteal bone formation during the first and second weeks following transfer, and thereafter, the graft continued to show active bone formation. In transverse section, the sharp processes became rounded. In the cancellous bone, both bone resorption and bone formation were noticeably activated early after transfer, although resorption predominated and the amount of the cancellous bone consequently diminished. The nonvascularized grafts showed "creeping substitution." The results suggest that morphologic adaptation occurs if living (i.e., vascularized) tail bones are transferred to long-bone femurs. PMID- 8438022 TI - Experimental rectus abdominis myocutaneous and rectus abdominis myoperitoneal flaps as urinary bladder wall substitutes in miniature swine. AB - An experiment was performed in Yucatan miniature swine to determine the feasibility and characteristics of musculocutaneous or musculoperitoneal flaps as urinary bladder wall substitutes. In five swine, a single-pedicle skin island flap (rectus abdominis myocutaneous, RAM/C) was sutured into the bladder. In five other swine the flap was a peritoneum island (rectus abdominis myoperitoneal, RAM/P). Three swine were sham-operated controls. The patches were in place for 20 weeks, remaining viable and elastic. Inflammation, maceration, and infection were absent. Skin patch histology was unchanged. The peritoneal patches became resurfaced with uroepithelium. The sham bladder volume (ml/kg body weight) did not differ significantly from RAM/P bladder volume (p = 0.54). RAM/C bladders were slightly smaller than shams (p = 0.11) and significantly smaller than RAM/P bladders (p = 0.03). Substitution of the bladder wall with RAM patch flaps is feasible. This is an important preliminary step toward our goal of nonenteral urinary bladder wall substitution. PMID- 8438024 TI - "Doctor, I would like you to close the skin": an invitation one can do without. PMID- 8438023 TI - The effect of microvascular anastomosis configuration on initial platelet deposition. AB - The propensity for platelets to bind at a native vessel anastomosis is thought to be related to subendothelial exposure, the presence of suture material, and local flow disturbances. By using an artificial microvascular graft to artificial microvascular graft anastomosis model that mimics the geometry and topography of a native microvascular anastomosis but which eliminates the endothelial and subendothelial contributions, the influence of the normal anastomotic configuration alone on initial platelet deposition was measured. Anastomotic and immediate downstream platelet deposition was not augmented by the presence of the anastomotic configuration alone. This suggests that the enhanced initial platelet deposition in the region of a native vessel microanastomosis is primarily related to the presence of injured endothelium and exposed subendothelium rather than to flow disturbances. PMID- 8438025 TI - Capsular contracture simulating myocardial infarction on ECG. AB - A patient is presented with severe bilateral class IV capsular contractures who presented 16 years after prepectoral breast augmentation with a "septal infarct" pattern on ECG. This abnormal ECG proved to be an artifact caused by unavoidable misplacement of the V2 and V3 leads because of the severe capsular contracture. Following open capsulotomy, normal anatomic lead placement was possible, and a normal ECG was produced. PMID- 8438026 TI - Malignant hemangiopericytoma of the forearm. AB - Hemangiopericytoma is a tumor that arises from primitive perivascular cells in many sites of the body. A painless tumor may be present for years. Malignant hemangiopericytoma of the upper extremity is rare, with only 14 cases previously reported in the English literature. Because of the often unpredictable behavior of this tumor, extended follow-ups are strongly recommended. PMID- 8438027 TI - Partial replantation after traumatic proximal lower limb amputation: a one-stage reconstruction with free osteocutaneous transfer from the amputated limb. AB - A case of immediate stump reconstruction following proximal leg amputation below the knee is reported. Additional length and sensation are conferred to the stump by free autotransplantation of a composite flap taken from the unsalvageable amputated leg. This flap provided 13 cm of vascularized tibia invested in the skin of the foot. This operative procedure facilitated the fitting of a prosthesis and preserved knee function despite an initial very proximal amputation. PMID- 8438028 TI - Simultaneous replantation of both lower legs in a child: a long-term result. AB - The progress of contemporary medicine and operative techniques makes it possible to successfully perform the simultaneous replantation of major segments of two extremities, especially in young patients, taking into consideration their high biologic potential. An adequate antishock management, hemotransfusion therapy in particular, at all stages of treatment is an indispensable condition of a favorable outcome of such operations. The method of lengthening the extremities using a distraction apparatus is rather promising for the improvement of functional results of replantations of major segments of the lower extremities. The use of this method makes it possible to broaden the scope of indications for such operations. PMID- 8438029 TI - Detection of gel implant rupture: a clinical test. AB - This report outlines a simple clinical test for detection of a ruptured smooth, predominantly gel breast implant in a noncontracted capsule. The test is rapid and extremely simple to perform and has been used by me since 1979. Approximately 630 patients meeting these criteria have been examined with this method, many annually. Five ruptured implants were detected, and there were no false-positive results. There also were no false-negative results, although only 72 patients had surgical confirmation of implant integrity. The radiographic measures helpful for detecting a ruptured gel implant are also discussed. In this series, the clinical test was more accurate than mammography for detecting implant rupture in the absence of capsular contracture. PMID- 8438030 TI - Cosmetic reconstruction of the mons veneris and lower abdominal wall by skin expansion as the last stage of the surgical treatment of bladder exstrophy: a report of three cases. AB - The results of the correction of the medial scar depression and diastasis of the pubic hair of the mons veneris in three postpuberal female patients operated on for bladder exstrophy are reported. The reconstructive surgery is carried out using skin expanders. The expanded skin is utilized to create two dermoadipose flaps to fill the medial depression, to outline again the public hair areas, and to allow sutures without tension. PMID- 8438031 TI - Chordee: different concept and new trend of treatment. AB - Chordee or ventral curvature of the penis is commonly associated with and occasionally without hypospadias. The usual recommended treatment is excision of the fibrous tissue that is responsible for the bowing. This results in a proximal retraction of the meatus. With a different concept and explanation of the ventral curvature, we treat this abnormal condition as a shortage of tissue. More than a hundred consecutive cases of chordee with and without hypospadias were treated by skin release and dorsal to ventral transposition of preputial skin as well as hypospadias repair. The whole procedure is simple, planned as a single-stage operation with less morbidity or fewer complications. The meatus is not pushed back proximally, no dissection distal to the meatus is performed, and there is no need for tissue excision. The results were very successful, with no recurrence of the ventral curvature. PMID- 8438032 TI - Gold lid loads. PMID- 8438033 TI - Is it a foreign-body reaction or enhancement of wound healing? PMID- 8438035 TI - FDAA bans sale on microwave ovens to women: an imaginary scenario. PMID- 8438034 TI - Reflex sympathetic dystrophy: a multimodality pain-management treatment. PMID- 8438036 TI - Ear cartilage graft on the hand joint. PMID- 8438037 TI - "Our" Freud. PMID- 8438038 TI - On the setting of analytic fees. PMID- 8438039 TI - A screen memory: my recollections and distortions of the 1950 film, Three Came Home. PMID- 8438040 TI - The analyst's use of humor. AB - The author presents two clinical vignettes involving the deliberate use of humor by the analyst, which appeared to help foster an atmosphere that promoted the analytic process. It is suggested that the analyst's use of humor conveyed information about his mental state and his attitude toward the patient which disconfirmed inhibiting expectations and thus increased the patient's ability to be self-reflective and to face painful affects. The potentially deleterious effects of humorlessness in the analyst are also discussed. PMID- 8438041 TI - On the value of explicit reconstruction. AB - Classical psychoanalysis provides a clinical method and a technique which enable us to help the patient undo primary process transformations of crucial organizing events and the fantasies about them, toward the end of understanding not only the original internal components of conflicts still persisting in the present, but the manner in which the patient originally constructed his or her unique pathogenic system of meaning. That technique involves explicit reconstruction. Private systems of meaning are frequently constructed around the apparently arbitrary contiguities of life, and only the reconstruction of those contiguities can reveal to the patient how he or she has understood and continues to understand the data of external perception. An extended clinical example is presented. PMID- 8438042 TI - Vincent: the self-portraits. AB - The self-portraits of Vincent van Gogh are examined in the context of his tragic life experience, ending in psychosis and suicide. The self-portraits are seen as repeated and unresolved efforts at self-exploration and self-definition in an attempt to add a sense of continuity and cohesion to a fragile and fragmented self-experience. The portraits are painted in mirror perspective; Vincent's search for identity is thus seen as mediated by the dynamics of the mirroring phenomenon. Further implications are explored in terms of processes of projection and introjection and their role in self-consolidation. PMID- 8438043 TI - Shedding the load--vasodilators in treating chronic heart failure. PMID- 8438044 TI - Echocardiography in chronic heart failure in the community. AB - A total of 128 patients from a single practice population who were receiving loop diuretics for treatment of presumptive cardiac failure were identified from prescribing data captured by the Medicines Monitoring Unit. A subgroup of 78 patients underwent echocardiography to determine the prevalence of true left ventricular systolic dysfunction in this population and the validity of the diagnosis of cardiac failure in primary care. A further 50 patients were studied to assess the workload generated by these patients for both primary health care and hospital services. The estimated prevalence of left ventricular systolic dysfunction was 0.84%, whereas 1.6% of the population received loop diuretics for this indication. A false-positive diagnosis occurred in 47% and was more likely in females (73%) than males (37%). Of all consultations 79% were seen by GPs, 14% as hospital out-patients and 7% as in-patients. Within the hospital general physicians have most contact with these patients. In summary chronic heart failure is common within the community, although the false-positive rate for diagnosis of this condition is high. GPs and general physicians treat the majority of these patients and should therefore receive continuing education regarding recent advances in this area. Echocardiography should be performed early in the management of all patients suspected of having cardiac failure. PMID- 8438045 TI - The clinical benefits of molecular medicine. PMID- 8438046 TI - DNA diagnosis of fatal fructose intolerance from archival tissue. AB - Hereditary fructose intolerance is a recessively-transmitted disorder of metabolism caused by deficiency of aldolase B in the liver, intestine and kidney, that responds favourably to an exclusion diet. The occurrence of fatal hepatorenal failure in a 16-year-old girl, who had received infusions of fructose and sorbitol during minor surgery, led us to suspect that she had suffered from hereditary fructose intolerance. Molecular analysis of leucocyte DNA obtained from her brother who had had a long-standing aversion to fruit and sugar, showed two previously unknown mutations in the aldolase B gene. An initiation codon mutation, M-1T, was inherited from the father, whereas Y203X, inherited from the mother, is a nonsense mutation that replaces a tyrosine codon by the ochre termination signal. The only source of genomic DNA from the index case was a fixed fragment of necrotic liver that had been obtained by needle aspiration postmortem and was embedded in paraffin wax. Analysis of aldolase B genes in this sample by procedures based on the polymerase chain reaction (PCR) confirmed the presence of both mutations in the proposita, the diagnosis of hereditary fructose intolerance, and the cause of death. PMID- 8438047 TI - Primary hypogammaglobulinaemia: a survey of clinical manifestations and complications. AB - The records of 240 patients with common variable immunodeficiency, seven with thymoma-associated hypogammaglobulinaemia and 44 patients with X-linked agammaglobulinaemia seen at this centre over the past 20 years, were reviewed. Although substantial advances have been made in treatment there continues to be a delay in diagnosis, as well as high mortality and morbidity rates. Hypogammaglobulinaemia is associated with a high incidence of chronic sinopulmonary infection, chronic diarrhoea, malignancy, joint disease and hepatitis. There is particular concern that infection with mycoplasmas and enteroviruses can be resistant to treatment. The high incidence of lymphoma and gastric carcinoma in patients with common variable immunodeficiency is high lighted. PMID- 8438048 TI - Murine typhus in Thailand: clinical features, diagnosis and treatment. AB - One hundred and thirty-seven patients with murine typhus were reviewed. A history of direct contact with rats was rare, and none gave a history of flea bite. No seasonal trend was observed. Clinical presentations included fever (100%), hepatomegaly (24%), rash (20%) and non-specific signs. Complications were uncommon but included jaundice, pneumonia, renal insufficiency and meningitis. Only two patients died. A single 200 mg dose of doxycycline significantly shortened the duration of fever: 79% were afebrile in 48 h, compared to 15% of the untreated group. PMID- 8438049 TI - Pleural involvement in the carcinoid syndrome. AB - Tissue fibrosis is a recognized complication of the carcinoid syndrome but pleural changes have not been described. Prompted by the finding of severe pleural thickening in two patients with the metastatic carcinoid syndrome but no thoracic metastases or previous pleural disease we reviewed the chest radiographs and CT scans in 50 patients with the carcinoid syndrome investigated from 1981 to 1990. Pleural abnormality was noted in 14 of the 50 patients (28%), five of whom had other possible causes for pleural disease. However, nine (18%) patients had 'idiopathic' pleural thickening. Pleural disease had developed within 2 years of the diagnosis in all cases, and seven of the nine patients had fibrosis elsewhere (heart valves, skin or mesentery). There were no features to suggest a more rapid disease progression in the patients with pleural disease. We suggest that the pleural abnormality is a complication of metastatic carcinoid disease. PMID- 8438050 TI - Mitochondrial myopathy associated with chronic zidovudine therapy in AIDS. AB - One hundred and eighteen consecutively identified AIDS patients, 88 of whom received zidovudine (1000-1200 mg/day), were followed for 1 year to investigate prospectively the relationship between zidovudine and myopathy. Clinical and biochemical evidence of proximal myopathy was seen in 7 of 41 patients (17%) who had been receiving zidovudine for more than 270 days, but in none of those on short-term therapy and in none of the controls. Serum creatine kinase levels rose a mean of 76 days (range 34-187) before the onset of clinical signs. Creatine kinase returned to normal within 4 weeks of cessation of zidovudine and strength returned within 8 weeks, though loss of muscle bulk persisted. Chronic malaise, anorexia and nausea accompanied the myopathy and remitted within 8 weeks of stopping zidovudine. Muscle histology in four patients with myopathy showed fibre size variation with atrophic, necrotic and degenerating fibres and an absence of inflammation. Ultrastructural studies showed glycogen-packed sarcoplasm, lipid droplets and grossly giant mitochondria. These abnormalities improved substantially after stopping zidovudine. Similar but less marked changes were seen in a zidovudine treated patient without myopathy, but were absent in one AIDS patient not taking the drug. Long-term zidovudine therapy is associated with a mitochondrial myopathy and the constitutional features suggest that it is part of a wider disorder affecting cellular function in other tissues. PMID- 8438051 TI - Necrotizing crescentic glomerulonephritis without significant immune deposits: a clinical and serological study. AB - To determine the spectrum of systemic diseases associated with pauci-immune necrotizing crescentic glomerulonephritis, we have analysed extra-renal manifestations, occurrence of extra-glomerular vasculitis and incidence and specificity of antinuclear cytoplasmic antibodies (ANCA) in 40 patients selected only on renal histological criteria. Extra-renal symptoms were unexpectedly observed in all patients but one, and were suggestive of vasculitis in 24. Extra glomerular vasculitis was seen in 18 kidney biopsies and four biopsies from other organs. Among the 33 patients with suspected or established vasculitis, 13 had presumed or biopsy-proven Wegener's granulomatosis, three had a macroscopic form of polyarteritis nodosa and 17 could not be adequately classified. An additional patient had clinical signs of Wegener's granulomatosis without clinical and histological evidence of vasculitis. ANCAs were detected in 28 of 33 and 25 of 34 sera tested by immunofluorescence and enzyme-linked immunoassay, respectively: 19 contained anti-myeloperoxidase antibodies and six had anti-proteinase 3 activity. Anti-myeloperoxidase and anti-proteinase 3 antibodies were present in all clinical subgroups but with various frequencies: anti-myeloperoxidase antibodies were more common (six of 12) than anti-proteinase 3 (four of 12) in patients with suspected or histologically proven Wegener's granulomatosis. Anti-proteinase 3 antibodies were 3- to 4-fold more common in patients with Wegener's granulomatosis than in those with systemic vasculitis of other causes (one of 12) or necrotizing crescentic glomerulonephritis without evidence of extra-renal vasculitis (one of 10). These results strongly suggest that pauci-immune necrotizing crescentic glomerulonephritis belongs to the broad spectrum of necrotizing vasculitides affecting glomerular capillaries. This study shows substantial improvement in renal prognosis and life expectancy with aggressive immunosuppressive therapy despite the older age of the patients, dissemination of the vasculitic process and often delayed diagnosis. PMID- 8438052 TI - Superinfection in HIV diseases. PMID- 8438053 TI - Superinfection in HIV disease. PMID- 8438055 TI - Delay to thrombolysis in myocardial infarction. PMID- 8438054 TI - Frequency of ventricular fibrillation and resuscitation success. PMID- 8438056 TI - Relationship between mitotic delay and the minimum dose rate of X irradiation required to stop cell proliferation. AB - When cells are subjected to irradiation, their progression through the cell cycle can be arrested. If the arrested cells are subjected to additional damage, their period of arrest is prolonged. Under continuous low-dose-rate irradiation, the cumulative nature of arrest time leads to a geometric increase in the arrest time as a function of the dose rate. Above a certain cell-line-specific dose rate, the arrest duration becomes infinite and cell proliferation ceases. We find that the lowest dose rate (critical dose rate) required to stop cell proliferation during continuous irradiation is the reciprocal of the mitotic delay per gray of high dose-rate irradiation. The calculated critical dose rates for X rays agree with those measured by Mitchell et al. (Radiat. Res. 79, 537-551, 1979), provided that the critical dose rate is identified with the minimum dose rate which allows no more than one population doubling. This specific identification of the critical dose rate is explained on the basis of cell cycle kinetics. A kinetic mechanism for cell cycle arrest and recovery leads to the critical dose rate as the reciprocal sensitivity for G2 arrest. PMID- 8438057 TI - Calcium receptor binding of cisplatin and terbium in human breast tumor cells after hyperthermia. AB - Terbium phosphorescence was used to investigate a thermosensitive calcium binding protein located in the plasma membrane of human MCF-7 breast tumor cells. The cells were pretreated at 25, 37, or 43 degrees C for 1 h, before binding experiments were performed at 25 degrees C. The delta Imax for the Tb(3+)-MCF/7 complex increased significantly after cellular exposure to 43 degrees C. The Kd for the Tb(3+)-MCF/7 complex did not change with the temperature. These results suggested that hyperthermia can unmask preexisting calcium binding sites on the surface of the plasma membrane, without affecting their affinity. After treatment at 43 degrees C, the quenching of the Tb(3+)-MCF/7 intensity by cisplatin was significantly greater than that at 37 degrees C. Hyperthermia was determined to increase the affinity of cisplatin for the calcium binding protein. The effect of hyperthermia on the calcium receptor binding of cisplatin is hypothesized to be the basis for the synergism between their cytotoxicities. PMID- 8438058 TI - Ionizing radiation down-regulates histone H1 gene expression by transcriptional and post-transcriptional mechanisms. AB - The cellular response to ionizing radiation includes growth arrest and DNA repair. However, little is known about the regulation of gene expression by this agent. The present studies demonstrate that exposure to ionizing radiation is associated with a dose-dependent decrease in histone H1 gene expression. Following treatment with 20 Gy, this effect was transient, detectable at 15-30 min, and maximal at 6 h. Nuclear run-on assays demonstrate that this down regulation is controlled at least in part by transcriptional mechanisms. We also demonstrate that inhibition of protein synthesis with cycloheximide abrogates the down-regulation of both histone H1 gene transcription and mRNA levels in irradiated cells. The results demonstrate that treatment with ionizing radiation is associated with a decrease in the stability of the histone H1 transcript, and that this effect is reversed by inhibition of protein synthesis. These findings demonstrate that ionizing radiation activates at least two distinct signaling pathways that control histone H1 expression at the transcriptional and post transcriptional levels. PMID- 8438059 TI - Cell killing induced by decay of 125I during the cell cycle: comparison of 125I antipyrine with 125I-bovine serum albumin. AB - The lethal effects induced by the decay of 125I in synchronized L5178Y cells were studied by suicide experiments. We used 125I-antipyrine, which is freely diffusible in cells, and 125I-bovine serum albumin (BSA), which remains outside the cells. Synchronized cells mixed with either 125I-antipyrine or 125I-BSA were frozen and stored at -196 degrees C for various periods to accumulate 125I decays. A clonogenic assay was used to measure the killing of these stored cells. Cells in G1-S and G2-M phases were more sensitive than those in late S phase for both 125I treatments. The ratio of survival in late S to that in G1-S (late S/G1 S) obtained by the decay of 125I-antipyrine, however, was much smaller than that obtained by the decay of 125I-BSA in the dose range examined. These results suggest that Auger electrons emitted from 125I-antipyrine cause a high-LET-type effect. The reason for the high-LET effect must be the intracellular localization of 125I-antipyrine and its closer contact with DNA. PMID- 8438060 TI - Effect of captopril on changes in rats' hearts induced by long-term irradiation. AB - The aim of this study was to test the efficacy of captopril, an angiotensin converting enzyme inhibitor and a known suppressor of fibrosis, in preventing late radiation-induced cardiac pathology. Myocardial functional, histochemical and ultrastructural-morphometric studies were done on perfused hearts of rats isolated 3 and 6 months after 60Co gamma irradiation with 20 Gy and age-matched controls. At each time the animals were divided into the following groups: nonirradiated controls; irradiated once with 20 Gy; irradiated as above and given daily doses of captopril; daily doses of captopril without irradiation. The results showed that captopril, while ameliorating the decrease in the indices of capillary function, increase in mast cells, fibrosis, number of atrial granules, and changes in nerve terminals, failed to prevent the progressive functional deterioration of the hearts after irradiation. These findings suggest that an intramyofiber derangement may be involved in the long-term myocardial complications of irradiation. PMID- 8438061 TI - Accelerated heavy particles and the lens. VIII. Comparisons between the effects of acute low doses of iron ions (190 keV/microns) and argon ions (88 keV/microns). AB - The nature of the RBE-LET relationship for radiation-induced effects in vivo is not well known in the high-LET range above about 100 keV/microns. Here, we compare the cataractogenic effects of acute doses of 190 keV/microns iron ions on the eyes of rats with those of 88 keV/microns argon ions. The RBEs of the two radiations cannot be distinguished statistically, both being between 50 and 200 at our lowest dose of 0.01 Gy and decreasing to between 2 and 14 at our highest dose of 0.5 Gy; these values are consistent with results obtained in vivo, both for cataractogenesis and for oncogenesis. For this end point, therefore, the RBE LET relationship probably varies very slowly between 88 and 190 keV/microns. On the basis of these studies with acute doses of 88 and 190 keV/microns particles, the detailed distribution in LET of the very high-LET galactic cosmic-ray dose to which astronauts in deep space are exposed may not be critical for the prediction of biological hazard. Such a conclusion might simplify the task of high-LET radiation risk estimation in space. PMID- 8438062 TI - Skeletal uptake and lifetime retention of 90Sr and 226Ra in beagles. AB - Skeletal uptake and retention of graded doses of ingested or injected 90Sr and injected 226Ra have been studied in 863 beagles; measurements of skeletal burden were made up to a maximum lifetime of 18.5 years. Doses ranged from 0 in 162 controls to levels that markedly reduced life span. Skeletal uptake of the administered doses averaged 2 to 2.3% for 90Sr fed to 388 beagles from midgestation to age 540 days, 33 to 35% for 45 dogs that were given single intravenous injections of 90Sr at age 540 days, and 37 to 45% for 226Ra given in eight fortnightly intravenous injections to 253 dogs from age 435 to 540 days. Skeletal retention was evaluated from the time when uptake ended until death, which occurred, on the average, at 14 to 14.5 years for the lower levels. Simple two-parameter power functions of the form SB(t) = at-b, with SB the skeletal burden, t the time after beginning of intake, and a and b fitted parameters, but corrected for radioactive decay, were used to describe the whole-skeleton retention of deposited 90Sr or 226Ra, as well as in 17 skeletal subgroups. The negative logarithmic slope, b, of these power functions for whole skeleton was about the same for both 90Sr and 226Ra, with an average value of 0.30 +/- 0.05 SD, indicating a common clearance mechanism. The lifetime average cumulative absorbed dose to irradiated skeleton varied from 0.38 to 107 Gy for beta rays in the 90Sr studies and from 0.94 to 167 Gy for alpha particles in the 226Ra studies. Daily dose rates to the skeleton for singly injected 90Sr fell rapidly after injection and declined to about 10% of the peak values late in life. Rates declined more slowly to 40-50% of peak values in other treatment groups. The time weighted average dose rate for fed 90Sr and injected 226Ra was a robust measure that declined only about 20% late in life compared to peak values. The lifetime average dose rate varied from 0.08 to 133 mGy day-1 for the 90Sr studies and from 0.21 to 162 mGy day-1 for the 226Ra studies. Lifetime doses to mandible and cervical vertebrae for the intermediate dose levels of fed 90Sr were calculated to be about 40% higher than the skeletal average. PMID- 8438063 TI - Photon activation of iododeoxyuridine: biological efficacy of Auger electrons. AB - Photon activation therapy is a binary system being investigated as a potential therapeutic modality to improve the treatment of malignancies, particularly the highly lethal and malignant brain tumor, glioblastoma multiforme. Its success relies upon the incorporation of a target atom in the immediate vicinity of a tumor cell's critical site, followed by the activation of this atom with photons of energies suitable for the induction of the photoelectric effect and its concomitant Auger cascades. The collective action of the Auger electrons imparts high-LET type damage at the critical site. Photon activation therapy uses iodine from stable iododeoxyuridine (IdUrd) as the target atom, and monochromatic photons above the K absorption edge of iodine (33.2 keV) as the activating agent. Although IdUrd is a cell-sensitizing agent, work described was designed to separate the biological efficacy due to sensitization from that of the Auger effect. Chinese hamster V79 cells with and without IdUrd in cellular DNA were irradiated at the X17B1 beam line in the National Synchroton Light Source of Brookhaven National Laboratory. Monochromatic photons above (33.4 keV) and below (32.9 keV) the K absorption edge were used to determine if any additional biological damage would accrue from the Auger cascades. The 33.4-keV photons were found to be a factor of 1.4 times more effective than 32.9-keV photons in damaging iodinated cells. The sensitizing effect, evaluated separately, was found to be a factor of 2.2 at 10% survival, regardless of photon energy. Thus the total therapeutic gain was 1.4 x 2.2 = 3.1. Irradiations of noniodinated control cells showed no difference in their response to energies above and below the iodine K edge. PMID- 8438064 TI - Recovery from radiation damage in mouse lung: interpretation in terms of two rates of repair. AB - A reanalysis was performed of the extensive data set obtained with fractionated irradiations of mouse lung reported by Travis et al. (Int. J. Radiat. Biol. 52, 903-919, 1987). The possibility was investigated that the poor fit of these data to the linear-quadratic model might have been the result of the presence of two rates of repair of sublethal damage instead of one. Therefore, the incomplete repair linear-quadratic model was adapted to incorporate two independent rates of repair and the data were analyzed using this two-component incomplete-repair model. The results which are subjected to certain qualifications with respect to the assessment of the validity of the confidence limits indicated the presence of two significantly different repair rates, corresponding to a fast-repair half time (t1/2) of 0.40 h (0.28, 0.53) and a slow t1/2 of 4.01 h (1.55, 6.57). A weight factor determined simultaneously indicated that the fast component has approximately four times more weight than the slow component. The alpha/beta value calculated for the entire data set using the same model was 3.8 Gy (3.0, 4.6), which is not significantly different from the alpha/beta of 3.6 Gy (2.8, 4.5) calculated for the 8- and 12-h data only, using the complete-repair linear quadratic model. An experiment specifically designed to test the significance of the fast-repair component was performed in which mouse lungs were irradiated with two equal dose fractions, separated by intervals ranging from 10 min to 6 h. Data obtained from this experiment allowed only one repair rate to be determined, corresponding to a t1/2 of only 0.4 h. This finding confirms the presence of a very fast repair rate in mouse lung. PMID- 8438065 TI - A Gompertz age-specific mortality rate model of toxicity from short-term whole body exposure to fission neutrons in rats. AB - A Gompertz age-specific mortality rate model was developed for toxicity resulting from a single dose of a toxicant resulting in nonrepaired injury that summates with natural (aging) injury. The model was applied to mortality data for male Sprague-Dawley rats subjected to short-term whole-body exposure to fission neutrons (D. Chmelevsky et al., Radiat. Res. 98, 519-535, 1984; J. LaFuma et al., Radiat. Res. 118, 230-245, 1989). The logarithmic-logistic function was used to relate the displacement of the Gompertz function with dose. Analysis of the age specific mortality rate provides a measure of total injury over time from combined neoplastic and non-neoplastic causes and can be used to calculate the relative biological effectiveness (RBE) of different radiation sources. It is a useful adjunct to conventional risk assessment paradigms, particularly for those toxicants such as fission neutrons which result in a large number of competing causes of death other than cancer. PMID- 8438066 TI - Assessment of radiation-induced lung injury in mice using carbon monoxide uptake: correlation with histologically visible damage. AB - Carbon monoxide uptake is a sensitive measure of lung injury, but its application to mice using the rebreathing technique has produced a nonlinear dependence of carbon monoxide uptake on mouse weight, in contrast to the linear relationship obtained in larger rodents using the single-breath technique. Improvements were made to the equipment and the procedures used in the rebreathing technique which resulted in linear relationships between uptake and weight in three mouse strains, CBA/J, C57BL/6J, and C57L/J. Sequential measurements were made on mice during the early and intermediate phases after irradiation of the thorax which demonstrated the development of injury in individual mice with considerable sensitivity. Estimates of the proportion of lung which was considered to be nonfunctional based on its histological appearance were obtained using alveolar ducts as sampling markers in 64 C57L/J mice between 10 and 31 weeks after irradiation. The deficit in carbon monoxide uptake was determined on the day of sacrifice for each mouse, and the results showed good correspondence to the histological estimate of the extent of damage. The correspondence between breathing rate elevation and the histological assay was not as good. PMID- 8438067 TI - Lack of differential radiosensitization of hypoxic cells in a mouse tumor at low radiation doses per fraction by cisplatin. AB - Korbelik and Skov (Radiat. Res. 119, 145-156, 1989) have reported that cis diamminedichloroplatinum (II) (cisplatin) shows substantial preferential radiosensitization of hypoxic cells in vitro at low radiation doses (1-4 Gy), and that the interaction seen with low doses of radiation is greatly diminished at high radiation doses. If such an interaction occurred with fractionated irradiation in vivo, it would be extremely important to radiation therapy, since the sensitizer enhancement ratios achievable in the low-dose region are higher than those achievable with current hypoxic cell radiosensitizers. We have tested this possibility in an experimental mouse tumor using fractionated irradiation under conditions in which the response of the tumor was determined by either its aerobic or its hypoxic cells. RIF-1 tumors were irradiated with 10 fractions of 1 4 Gy every 12 h with cisplatin given either as 12 mg/kg once before the first radiation dose or as 1.2 mg/kg at various times prior to each radiation dose. The tumors were irradiated with or without a clamp applied 2-3 min before each radiation dose. The effectiveness of the treatments was assayed by regrowth delay. Cisplatin caused a similar regrowth delay when used alone in both clamped and nonclamped tumors and produced a similar additive or supra-additive interaction when used with the 10 fractionated radiation schedule whether the tumors were hypoxic or aerobic. Our data suggest that cisplatin does not show any preferential radiosensitization of hypoxic cells with low-dose multifraction irradiation in this tumor, although a clear schedule-dependent interaction between the drug and radiation was seen for both aerobic and hypoxic tumors. PMID- 8438068 TI - Longitudinal study of astronaut health: mortality in the years 1959-1991. AB - We conducted a historical cohort study of mortality among 195 astronauts who were exposed to space and medical sources of radiation between 1959 and 1991. Cumulative occupational and medical radiation exposures were obtained from the astronaut radiation exposure history data base. Causes of death were obtained from obligatory death certificates and autopsy reports that were on file in the medical records. There was a total of 20 deaths that occurred during the 32-year follow-up period of which 16 were due to accidents. The all-cause standardized mortality ratio (SMR) was 181 (95% confidence interval 110, 279). There was 1 cancer death in the buccal cavity and pharyngeal ICD-9 rubric whose occurrence was significantly beyond expectation. Mortality for coronary disease was 53% lower than expected (2 deaths; SMR = 47; 95% confidence limits 5, 168). The crude death rate for 12 occupationally related accidents was 445 deaths per 100,000 person-years and was an order of magnitude greater than accidental death rates in the mining industries. The SMR of 1346 for fatal accidents was significantly beyond expectation (16 deaths; 95% confidence limits 769, 2168) and was similar to SMRs for accidents among aerial pesticide applicators. The 10-year cumulative risk of occupational fatalities based on the exponential, Weibull, Gompertz, and linear-exponential distributions was 10%. Mortality from motor vehicle accidents was slightly higher than expected, but was not significant (1 death; SMR = 165; 95% confidence limits 2,922). Radiation exposures from medical procedures accounted for a majority of cumulative dose when compared with space radiation exposures. Overall, it was found that astronauts are at a health disadvantage as a result of catastrophic accidents. PMID- 8438069 TI - Similar heat-induced cell cycle delays in the clonogenic and nonclonogenic fractions of a thermotolerant population. AB - We have tested the theory that a faster rate of recovery from thermal damage in thermotolerant cells relative to nontolerant cells is the critical factor which confers heat resistance. We measured the rate of recovery from the heat-induced cell cycle delay in Chinese hamster ovary cells, since this delay is shortened in thermotolerant cells (i.e., exhibits thermotolerance) and can be measured in individual cells. Individual thermotolerant cells were followed by discontinuous microscopic observation from shortly after heating, through the first mitosis after heating, until a colony formed or failed to form by 8 days. The heat induced delay in the clonogenic and nonclonogenic fractions was the same. This shows that the rate of recovery from the cell cycle delay was not the determining factor as to whether or not a cell survived to form a colony. Either additional factors are involved or the rate of recovery from the cell cycle delay plays no role in cell survival. These data show the importance of determining whether a faster rate of repair of thermal damage is specific for the clonogenic fraction, since most if not all types of thermal damage are likely to be repaired more quickly when thermotolerant and nontolerant cells are compared at isodose. PMID- 8438070 TI - On the question of the cause of the initial slope of survival curves. AB - In the double-strand break (DSB) model, the initial slope (alpha) of the survival curve is determined by the number of DSBs remaining unrepaired at a certain time after irradiation. There are three types of calculations which confirm the validity of this approach. First, the model quite reasonably predicts the low-LET alpha values for Chinese hamster V79, mouse L5178Y-R, normal fibroblast, ataxia telangiectasia (AT), and Ehrlich ascites tumor (EAT) cells using the measured values of the cellular DNA content, the radiation yield for DSB induction, the time constant for DSB repair, and the time available for DSB repair. Second, this approach correctly predicts an increase in alpha values for V79 and Chinese hamster ovary (CHO) cells due to postirradiation treatments with hypertonic saline or a high concentration of araA. These calculations are based on the duration of the DSB repair block induced by those treatments. Third, a fair agreement between the predicted and measured initial slopes for 3- to 4-MeV alpha particles was obtained for normal fibroblast, EAT, V79, CHO, Chinese hamster HS 23, C3H 10T1/2, and lung epithelial cells. However, the alpha values for AT and xrs-6 cells were overestimated. The calculation of high-LET alpha values uses the experimental values of the relative increase in the DSB repair time constant and in the radiation yield for DSB induction for alpha particles in comparison with those for X rays. PMID- 8438071 TI - Adenovirus facilitation of molecular conjugate-mediated gene transfer. PMID- 8438072 TI - Progress and perspectives in human hepatitis B virus research. PMID- 8438073 TI - The epidemiology and control of hepatitis B in sub-Saharan Africa. PMID- 8438074 TI - Biotic-abiotic mechanisms for long-term preservation and reemergence of influenza type A virus genes. PMID- 8438075 TI - Detection and significance of HIV sequences in HIV infection. PMID- 8438076 TI - Defective parvoviruses may be good for your health! PMID- 8438077 TI - Assembly of bacteriophage P22: a model for ds-DNA virus assembly. PMID- 8438078 TI - Clinical and public health virology: a continuous task of changing pattern. PMID- 8438079 TI - Rabies: a new look at an old disease. PMID- 8438081 TI - Stereotactic treatment of brain tumors with radioactive implants or external photon beams: radiobiophysical aspects. AB - We perform calculations, based on the linear-quadratic model, to assess the biologically effective doses (BED) of tumor and normal tissue in the stereotactic irradiation of brain tumors with either radioactive implants or radiosurgery techniques. Treatment protocols for radiosurgery and radioactive implants, as obtained from the literature, are reviewed and compared. A figure of merit is defined to be the ratio of tumor to normal tissue BED, expressed in units of Gy10/Gy3. These comparisons indicate a clear radiobiological advantage for brachytherapy, unless the radiosurgery is to be delivered in a large number of fractions. The differences in dose uniformity, and in the volume of normal tissue encompassed by the high dose regions, are factors that may also influence clinical results. PMID- 8438080 TI - Craniopharyngioma--a long-term results following limited surgery and radiotherapy. AB - Between 1950 and 1986 173 patients with craniopharyngioma were treated at the Royal Marsden Hospital with external beam radiotherapy either alone or following surgery. Four patients had complete tumour excision, 21 subtotal and 78 partial resection, 14 had biopsy alone, 34 aspiration alone and 22 had no surgery directed at tumour eradication. Seventy-seven (45%) were children (aged < 16 years). The 10 and 20 year progression-free survival (PFS) rates were 83% and 79%. There were no independent prognostic factors for PFS. The 10 and 20 year survival rates were 77% and 66% at a median follow-up of 12 years. After adjustment for mortality in the normal population, age and technique of radiotherapy (which corresponded with era of treatment) were significant independent prognostic factors for survival. The risk of death (corrected for mortality from natural causes and controlling for radiotherapy technique) for age groups 16-39 and > or = 40 was 0.58 and 0.40 respectively, relative to a risk of 1.0 for the age group < 16 years. Survival and PFS were not influenced by the extent of surgical excision. Visual field defect improved after radiotherapy in 36% of patients (38/106) and visual acuity in 30% (27/91). No patient developed radiation optic neuropathy. We conclude that limited surgery and radiotherapy achieve excellent long-term tumour control and survival with low morbidity. PMID- 8438083 TI - External beam radiotherapy in the management of ovarian carcinoma. AB - Between 1970 and 1983, 345 patients with ovarian cancer clinical stage I, II, and III were irradiated postoperatively. Five-year NED survival was achieved in 41.7% of patients. The most important prognostic factors were histological grade and clinical stage of cancer. Postoperative external beam radiotherapy appeared to be highly efficient for the patients with microscopic residual disease, giving 70% 5 year survival, and moderately efficient for patients with small, i.e. < or = 3 cm in diameter residual disease, giving 40% 5-year survival. The optimal technique of irradiation appeared to be the irradiation given to the entire abdominal cavity with additional irradiation coned down to the pelvis. External beam radiotherapy was ineffective in patients with gross residual disease, i.e. > 3 cm in diameter, and useless as palliative treatment given to patients with inoperable cancer of the ovary. PMID- 8438082 TI - Effect of intersource spacing on local control and complications in brachytherapy of mobile tongue and floor of mouth. AB - From 1971 to 1988, 133 T1 and 141 T2 biopsy-proven squamous cell carcinomas of mobile tongue and floor of mouth were definitively managed by Iridium-192. Implantations were performed using either guide gutters or afterloading plastic catheters. The prescribed dose at the reference isodose (85% of the basal dose rate, Paris system) was 60-70 Gy. Total dose was not adjusted to dose rate or tumor volume. Results of the 274 implants have been analysed to look for a possible influence of intersource spacing on local control and necrosis. Follow up for patients free of local recurrence is 1-180 months with median of 35 months. The 274 tumors were divided into two groups according to intersource spacing: 9-14 mm (n = 204), and 15-20 mm (n = 70). At 5 years, the estimated local control (Kaplan Meier) was 86% and 76%; respectively (p = 0.13); the necrosis rate was 33% and 46%, respectively (p = 0.04). Multivariate analysis shows that dose and activity of wires were significantly related to local control, while only tumor site was predictive of necrosis; there was a non statistically significant relationship between intersource spacing of wires and local control (p = 0.055). When considering only patients with oral tongue cancers, necrosis was significantly related to activity of wires (p = 0.013), and there was a non-significant trend to a relationship between necrosis and intersource spacing (p = 0.066) and tumor diameter (p = 0.065). For patients with floor of mouth cancer, none of these factors was significantly related to necrosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8438084 TI - Pilocarpine and carbacholine in treatment of radiation-induced xerostomia. AB - Twenty-four patients with radiation-related xerostomia were treated with oral pilocarpine solution 6 mg t.i.d., and after a 4-week drug-free period 16 of these patients were treated with carbacholine 2 mg tablets t.i.d. Basal and stimulated whole saliva flow rates were measured before commencing the drug treatment, and after 1 and 12 weeks on treatment. On a subjective linear scale both pilocarpine (p = 0.01) and carbacholine (p = 0.02) improved mouth moistness. Only 2 of the 8 patients with no basal or stimulated saliva flow reported some subjective benefit from the drug treatment, whereas all 8 patients with less severe xerostomia improved (p = 0.007). However, the salivary flow rates measured 12 h after the last drug dose did not improve with either drug. Both drugs were generally well tolerated. It is concluded that both drugs may be useful in the treatment of radiation-induced xerostomia among patients with residual salivary function. PMID- 8438085 TI - Thermoradiotherapy in locally advanced deep seated tumours--thermal parameters and treatment results. AB - From October 1987 to December 1990 a total of 37 patients with deep seated tumours of the pelvis (n = 34), the abdomen (n = 2), or lower leg (n = 1) were treated with radiotherapy and regional hyperthermia. Hyperthermia was produced by the BSD-1000 system and the annular phased array (AA) applicator usually driven at 60-80 MHz, or the BSD-2000 system and the Sigma-60 (S 60) applicator usually driven at 70-90 MHz. Detailed thermal mapping and temperature analysis was performed on 29 patients. The overall mean maximum, average and minimum temperature observed was 42.9 +/- 2.4 degrees C, 40.9 +/- 1.5 degrees C, and 39.3 +/- 0.9 degrees C for all treatments. The time-averaged tumour temperatures achieved in 20%, 50% and 90% of all measured temperature sites were 41.8 +/- 2.1 degrees C (T20), 40.9 +/- 1.6 degrees C (T50), and 39.9 +/- 1.2 degrees C (T90). In addition, the overall mean maximum, average and minimum temperature measured in normal tissue was 42.4 +/- 1.4 degrees C, 40.6 +/- 1.0 degrees C, and 39.2 +/- 0.9 degrees C. The time averaged normal tissue temperatures achieved in 20%, 50% and 90% of all measured temperature sites were 41.3 +/- 1.1 degrees C, 40.6 +/- 1.1 degrees C, and 39.6 +/- 1.0 degrees C. In 36 assessable patients, the overall objective response rate was 31%: 2 complete responses (CR) and 9 partial responses (PR). PMID- 8438086 TI - Intratumoral pO2 predicts survival in advanced cancer of the uterine cervix. AB - Experimental evidence suggests that the hypoxic fraction in a solid tumor may increase its malignant potential and reduce its sensitivity towards non-surgical treatment modalities (e.g. standard irradiation, certain anticancer agents). However, the clinical importance of tumor hypoxia remains uncertain since valid methods for the routine measurement of intratumoral O2-tensions in patients have so far been lacking. A clinically applicable standardized procedure has been established which enables the determination of intratumoral oxygen tensions in advanced cervical cancers by use of a computerized polarographic needle electrode histography system. Tumor oxygenation as measured by this method represents a novel tumor feature which can be individually determined for each tumor and which is independent from other known oncological parameters. The results of an interim analysis of an open prospective clinical trial to evaluate the prognostic significance of tumor oxygenation based on the survival data of the first 31 patients are presented. Fifteen patients have been treated by primary radiation, 11 patients received multimodality therapy including irradiation. After a median follow-up of 19 months (range 5-31 months), Kaplan-Meier-life table analysis showed significantly lower survival and recurrence-free survival for patients with a median pO2 of < or = 10 mmHg compared to those with better oxygenated tumors (median pO2 > 10 mmHg). The Cox proportional hazards model revealed that the median pO2 and the clinical stage according to the FIGO are independent, highly significant predictors of survival and recurrence-free survival. We conclude from these preliminary results that tumor oxygenation as determined with this standardized procedure appears to be a new independent prognostic factor influencing survival in advanced cancer of the uterine cervix. PMID- 8438087 TI - Evaluation of isoeffect formulae for predicting radiation-induced lung damage. AB - An experiment has been performed in which fractionated irradiation was given to the whole thorax of Sprague-Dawley rats with schedules chosen so that doses per fraction and overall treatment time were changed independently. Damage was monitored by lethality. The data have been analyzed to yield dose per fraction and time parameters using multiple non-linear regression analysis. The results show that a linear-quadratic cell survival formula, extended to include an exponential time component to account for proliferation or slow repair during the treatment, can predict isoeffective doses to within 7% accuracy over a wide range of times (3.5-49 days) and doses per fraction (1.8-10.2 Gy). Other isoeffect formulae based on the linear-quadratic and empirical power law functions were also evaluated. A linear-quadratic formula with a time dependent alpha parameter fitted the data particularly well. This result suggests an alternative underlying mechanism and requires further investigation. PMID- 8438088 TI - Accelerated repopulation of intestine post-irradiation following intraluminal injection of a mucosal cell suspension or its supernatant. AB - The injection of (1-7) x 10(5) mucosal cells into the intestinal lumen at 4 h after 14 or 18 Gy increased the number of intestinal microcolonies (> or = 10 cell foci) and microclusters (4-9 cell foci) when assayed at day 3. The effects were less when (a) the interval between irradiation and injection was increased to 20 h, (b) the assay time was increased to 4 days or more, (c) a cell supernatant was injected instead. The data indicate that the injections stimulated earlier regeneration. The effect of the supernatant suggests that the stimulation is mediated through a humoral factor. PMID- 8438089 TI - Micronuclei expression in tumors as a test for radiation sensitivity. AB - Dose-effect curves were determined for the frequency of micronuclei and impairment of cell clonogenicity from two types of tumours of different sensitivity irradiated in situ. Micronucleated cells were measured 24, 48 and 72 h after treatment. The quantitative relationships between cell reproductive death and the induction of micronuclei are the same for both tumours. PMID- 8438090 TI - Influence of cisplatinum on intestinal tolerance to photon and neutron irradiation in mice. AB - The hypothesis that cisplatinum (c-DDP) interacts with radiation by inhibiting the cellular repair capacities, was tested by comparing the interaction of c-DDP with low-LET (60Co gamma-rays) and high-LET radiation (d(50) + Be neutrons) in mice. The biological endpoint was lethality, 6 days after total body irradiation (early intestinal tolerance). The dose modifying factor was 1.80 +/- 0.25 for c DDP plus 60Co gamma-rays, and 1.97 +/- 0.3 for c-DDP plus neutrons. As less repairable damage is induced by fast neutrons than by photons, this suggests that, in this system, the interaction between radiation and c-DDP is not explained by repair inhibition but is purely additive. PMID- 8438091 TI - Diagnosis and treatment of spontaneous canine brain tumors with a CT scanner. AB - Spontaneous brain tumors in 25 pet dogs were diagnosed and treated with a modified CT scanner. Five or more weekly 9-Gy fractions resulted in marked clinical improvement in most dogs and a significant decrease in tumor size in many dogs without adverse effects from the radiotherapy. PMID- 8438092 TI - Toxicology of daily administration to mice of the radiation potentiator SR 4233 (WIN 59075). AB - We have investigated the feasibility of administration of an effective dose of the hypoxic cytotoxin, SR 4233, Monday-Friday daily for 6 weeks. From a thorough hematological, histopathological and clinical chemistry evaluation throughout the course and during a 3-week recovery period, we conclude that daily administration of a radiopotentiating dose of SR 4233 in mice is well tolerated and that bone marrow suppression is likely to be the dose-limiting toxicity. PMID- 8438093 TI - Evaluation of brachytherapy implants using the "natural" volume-dose histogram. AB - The "natural" volume-dose histogram as described by Anderson visualises graphically even small differences between source arrangements, making it a useful tool to compare planned and realised source configurations. In this study the histogram is applied to demonstrate that the introduction of an applicator in oral cavity implants or of iridium wire spacers used as templates in bladder implants improved the quality of the implants considerably, resulting in close agreement between the planned and the realised source configuration. PMID- 8438094 TI - Snoring and sleep apnoea. PMID- 8438095 TI - Tropical eosinophilia: a review. PMID- 8438096 TI - The effect of salbutamol controlled release on airways responsiveness to inhaled methacholine in mild asthmatic subjects. AB - Single doses of inhaled bronchodilating agents have been shown to reduce airways responsiveness (AR) in both normal and asthmatic individuals. The longer term effects of these treatments on airways responsiveness are less clear. We have studied the effects of 4 weeks of treatment with oral salbutamol controlled release (SCR) (8 mg b.d.) on airways responsiveness in mild asthmatics in a double-blind, placebo-controlled study. Airways responsiveness to inhaled methacholine, baseline FEV1 and plasma salbutamol levels was assessed 6 h, 48 h and 4 weeks after commencing treatment and again 24 h and 72 h after cessation of medication. When compared to placebo, SCR significantly attenuated AR at the 48-h time point only. There were no increases in AR recorded at any of the post treatment time points. In addition, there were no significant differences in baseline FEV1 at any of the time-points studied, when compared to placebo. The change in AR at 48 h after starting treatment was probably due to functional antagonism of smooth muscle contraction. Importantly, there were no increases in AR recorded at either of the post-treatment time points. PMID- 8438097 TI - Bronchial hyperresponsiveness in patients recovering from acute severe asthma. AB - Bronchial hyperresponsiveness is widely recognized as a marker of airway inflammation in asthma. The degree of bronchial hyperresponsiveness following acute severe attacks of asthma and the time course of its recovery has not previously been studied. Bronchial responsiveness to histamine was measured in 18 unselected patients admitted to hospital because of acute severe asthma, during their acute admission, and geometric mean PD20 histamine was 0.08 (range 0.02 0.32) mumol. In nine patients, further measurements were performed at 3-4 and 12 weeks following discharge. Geometric mean PD20 histamine was 0.09 mumol acutely, 0.23 mumol at 3-4 weeks (n = 9, p = 0.05 by analysis of variance) and 0.59 mumol at 12 weeks (n = 8, P = 0.04). For the eight patients studied at 12 weeks, a mean 10.3-fold increase in PD20 was shown, with no suggestion of a maximum effect having been achieved. In contrast, spirometry had returned to the normal range by 4 weeks. The dissociation between improvement in bronchial hyperresponsiveness and spirometry is of interest. The delayed reduction in hyperresponsiveness may have important clinical implications for the duration of anti-inflammatory corticosteroid treatment following acute severe asthma. PMID- 8438098 TI - Nebulized sodium cromoglycate in preterm infants--protection against water challenge-induced bronchoconstriction. AB - Nebulized water is an effective bronchoprovocative agent in asthmatic adults and children. The aim of this study was to assess the bronchoconstrictor effect of this agent in preterm infants studied at follow-up and if their response to it was altered by pre-treatment with nebulized sodium cromoglycate. Lung function, thoracic gas volume and airway resistance, was measured by whole body plethysmography and specific conductance (SGAW) calculated. Measurements were made before and after nebulized saline, nebulized water (first water challenge), nebulized sodium cromoglycate and again nebulized water (second water challenge). There was no significant change in SGAW following either normal saline or sodium cromoglycate. In nine infants SGAW deteriorated by more than 16% (twice the coefficient of variation of the measurement) after the first water challenge but only in one after the second water challenge (P < 0.01). We conclude that nebulized water is an effective bronchoconstrictor in preterm infants and that sodium cromoglycate can protect against this challenge. PMID- 8438099 TI - Pneumothorax in patients with AIDS. AB - Eighty-seven inpatients were treated for 93 episodes of Pneumocystis carinii at St Mary's Hospital between January 1989 and December 1990. During this period, 298 patients with the acquired immunodeficiency syndrome (AIDS) were treated at this hospital. Sixteen episodes of pneumothorax occurred and 12 of these, occurring in ten patients, were unrelated to procedure. In six of 12 (50%), the pneumothoraces occurred concurrently with Pneumocystis carinii pneumonia (PCP) and in ten (83%) cases there was a past history of PCP. Bilateral pneumothorax occurred in five cases (42%). In seven (58%) of the cases, patients had been using aerosolized pentamidine as prophylaxis for PCP. This retrospective study confirms the association of pneumothorax with current PCP and also shows an association with previous infection. The use of aerosolized pentamidine was not associated with pneumothorax development. It is important to suspect pneumothorax in a patient with PCP who deteriorates acutely. The high incidence of bilateral pneumothorax means that pleurodesis should be considered early. PMID- 8438100 TI - Influence of simulated mucus on cough sounds in cats. AB - Although in the clinic the presence of mucus in the airways is known to be an important factor influencing the sound of coughing in pathological conditions, this observation has not been established experimentally. We have substituted mucus in the airways of anaesthetized cats with 0.5 ml of natural undiluted egg albumin (EA) from hens' eggs, or with 1 ml of 10% pig gastric mucin (PGM) in saline. There were obvious changes in the character of cough sounds and significant increases in the intensity of the sounds (+76% with EA, +36% with PGM). The intensity of cough efforts significantly increased but only in the cats with addition of PGM (mean 30%). Removal of EA or PGM caused the opposite effects, a decrease in cough sounds (-41%) and intensity of cough effort (-52%), with simultaneous changes in the character of the cough sounds. There were no clear-cut patterns of cough sounds as has been described for humans. The cough sounds were often present not only during the expiratory phase of cough but also during the inspiratory phase. The results establish an important role of mucus in the airways in the creation of cough sounds. PMID- 8438101 TI - The aging lung: an epidemiological perspective. PMID- 8438102 TI - Effect of experimental lung oedema on cough sound creation. AB - We have assessed the importance of changes in lung structure on the pattern of cough sound and its creation with 13 anaesthetized cats. Acute lung injury with oedema was induced by i.v. administration of a mixture of fatty acids. Cough was elicited by mechanical stimulation of the mucous membranes of the airways and was evaluated by its intensities of effort and sound before and up to 2 h after administration of the fatty acids. Changes of cough sound pattern were not definitive, there being no typical alterations. The cough effort and sound intensities, induced from the trachea, consistently decreased (by 70-80% in both cases). The cough efforts immediately after induction of oedema were transiently abolished in some cats. The cough values induced from the larynx similarly decreased at 5 min (51-57%) but subsequently gradually returned to control values. There were significant correlations, both for coughs induced from the trachea and from the larynx, and for changes in intensity of efforts compared with sounds. Thus, pathological changes in the lungs modify the intensities both of cough efforts and their associated sounds. PMID- 8438103 TI - Communicating the diagnosis of lung cancer. AB - In order to assess their reaction to the information given, 50 patients underwent a semi-structured interview with a social worker within 1 week of having been told the diagnosis of lung cancer. There were 32 men and 18 women with a mean age of 63 (range 38-82) years. Thirty-eight (76%) belonged to Registrar General social class IV or V, and 45 (90%) had left school at the age of 15 years. Two patients were unaware of the diagnosis despite having been told that they had lung cancer. Two patients would have preferred not to have been told the diagnosis and two were unsure, while 46 (92%) felt that telling them the diagnosis truthfully had been correct. No patient felt that they had been given too much information, but 13 (26%) indicated a lack of information about prognosis. Despite being told 'bad news', 31 (62%) felt more reassured after their interview with the doctor, 5 (10%) felt less reassured, and 14 (28%) were uncertain. Twenty-one (42%) patients were experiencing a sense of guilt or regret at having smoked. Many patients had concerns about specific symptoms which they expected to suffer. In general, patients wanted to be told their diagnosis truthfully and required a high level of information. Many patients felt reassured by the discussion of such details. PMID- 8438104 TI - Macroscopic hematuria after a respiratory tract infection. PMID- 8438105 TI - Prescribed respiratory diseases in the 1990s. PMID- 8438106 TI - Blood gas techniques. PMID- 8438107 TI - Adult cystic fibrosis: current issues in a regional unit. PMID- 8438108 TI - [Skin cancers following organ transplantation: clinical and therapeutic approach]. AB - Three of the most frequent cancers occurring in transplant recipients affect the skin: Kaposi's sarcoma and spino- and baso-cellular carcinomas. The two latter neoplasms are often preceded by precancerous lesions such as keratosis, warts, porokeratosis and keratoacanthomas. We describe the clinical presentations of these lesions and detail the possible therapies in each case: local treatment, surgery, modulation of immunosuppression, and chemotherapy. PMID- 8438109 TI - [Drug antagonism]. AB - The mechanisms responsible of either a loss of therapeutic efficiency or a beneficial cancellation of toxic phenomena are reviewed. References are specifically made to antagonists of anti-vitamin K, oral contraceptives, antihypertensive drugs and statin. Concerning the antidotes, the importance of anti-digoxin antibodies, naloxone and flumazenil is emphasised. PMID- 8438110 TI - [Surgical interruption of the inferior vena cava]. AB - The historical review of the different techniques of inferior vena cava interruption allows to take into consideration the improvement in the treatment and prophylaxis of thromboembolism. On the one hand, technological progresses led to less invasive, often endoluminal surgical procedures. On the other hand, owing to administration of anticoagulant and fibrinolytic drugs, the indications of permanent and temporary vena cava filters become clearer and more precise. PMID- 8438111 TI - [Gynecological cancer and pregnancy]. AB - The available data regarding the impact of pregnancy on the course of gynecologic cancers and the effects of the malignant processes and their treatments on both the mother and the fetus are analyzed in the present work. The incidence of specific gynecologic cancers in pregnant women parallels that in woman of child bearing age in general. Cervical cancer is the most common followed by breast and ovarian cancer. The review of the recent literature indicates that for equivalent clinical stage, maternal age and lymph node involvement, survival rate of patients affected with gynecologic cancer during pregnancy is similar to those of non-pregnant women. A conflict between maternal therapy and fetal well-being is frequently observed in cases of invasive gynecologic cancer and a multidisciplinary approach is crucial to optimal treatment of the mother and her fetus. PMID- 8438112 TI - [Clinical applications of positron emission tomography]. AB - Positron emission tomography (PET) is a non invasive method of medical investigation which allows visualization and quantification of functional and metabolic data at the level of target organs. PET gives access to biological data on regional blood flow, energetic metabolism, synthesis and binding processes. In the brain, PET allows the study of different processes related to neurotransmission. PET provides data on cellular changes related to injuries, dysfunctions or abnormal proliferation. Diagnostic value of PET informations has been documented in several diseases, mainly in neurology, cardiology and oncology. The expected development of PET is related to advances in new radiotracers chemistry. PMID- 8438113 TI - [Medical confidentiality and insurance]. PMID- 8438114 TI - [Meeting in a Canadian university]. PMID- 8438115 TI - [Pulmonary embolism]. PMID- 8438116 TI - [Chronic abdominal pain and eosinophilia in a patient from Southern Italy]. AB - Strongyloidiasis is a parasitic disease which occurs not only in tropical regions, but to some extent in the South of Europe. Diagnosis is often difficult because of a polymorphic clinical picture and low larvae excretion in the stool. A case of an Italian patient suffering from a long-standing intestinal strongyloidiasis is reported. Diagnosis was made only after a long time and after a couple of superfluous examinations. Several treatment attempts were necessary to eradicate the infection. PMID- 8438117 TI - [AIDS and tourism. What is essential for clinical practice]. AB - The Swiss spend in the average 7% of their income for travelling and thus belong to the nation most eager to travel. Next to the technical preparation of a trip, medical prevention is equally important. Unfortunately, many physicians limit their activities around travelling to prescriptions for common troubles of travelling and to recommendations and measures for prophylaxis such as vaccinations or antimalaria drugs. This however, often singular visit by healthy 'patients' offers a good opportunity to address the subject of HIV/AIDS considering the various reasons for a risk of increased infection. The following article offers guidelines for such a conversation. PMID- 8438118 TI - [A case from practice (263). Giardia lamblia infection of the intestines]. PMID- 8438119 TI - [Follow-up drug treatment in the practitioner's office]. AB - The therapeutic drug monitoring begins to extend from specialized laboratories into the practitioners office. A systematic approach to these new problems is, therefore, recommended, following these guidelines: The rationale for measuring a drug level must be established. The precision of technical equipment and employed methods has to be optimal. The practicability and reliability of the methods (accuracy, precision, intra- and inter-series, variability) have to be assessed, and quality-control is mandatory. A result must be interpretable. Next to analytical precision, the result has to be attributed unequivocally to a sample, which in turn had to be collected under optimal circumstances. Finally, drug monitoring has to be an integral part of individual therapy plans. In this context understanding the therapeutic range and the pharmacokinetics is essential. Competences needed to manage an entire drug monitoring program are thus many-fold. Only a multidisciplinary team appears able to provide sufficient expertise. The conditions implied in this development burden a medical office financially by needed material and personal resources. PMID- 8438120 TI - [What studies should be done in syncope?]. AB - Fainting (short loss of consciousness) is a frequent reason for a consultation in a general practitioner's or cardiologist's office. Four main causes are recognized commonly: cardial with auriculo-ventricular block and arrhythmias, vascular in particular vaso-vagal syncopes, neurologic and other causes. In 38 to 47% of the patients no etiology is found: these are syncopal attacks of unknown origin. The first diagnostic step comprises noninvasive investigations. A 24-hour recording of the ECG or a 'long strip' improve the diagnostic rate by 10%. They are particularly useful for sick sinus syndromes. The head-up tilt-test has been developed recently. It is very useful for detection of vagovasal syncope and permits to understand the pathophysiology and the therapeutic consequences of these disorders. This test plays a particular role for the diagnosis of syncopes of unknown causes and shows in 24 to 75% of the cases pathologic results. Patients at high risk for ventricular arrhythmia can be recognized by ECG with high amplification. Doppler investigation of the neck vessels, however, seems to be of low diagnostic value in syncopes. Invasive measures are the last line resort. Electrophysiologic studies provide criteria that are well defined. They are useful for detection of ventricular dysrhythmias and conduction disorders. This latter approach is reserved to patients with negative noninvasive tests and in particular with cardiopathy. The approach to syncope and the power of noninvasive and invasive tests is thus well established. However, in a certain number of patients the cause for fainting is not disclosed. Fortunately mortality is low in this particular group. PMID- 8438121 TI - [A case from practice (264). Branchial cysts (lateral neck cysts). Ethanol and hashish abuse]. PMID- 8438122 TI - A good manager has to delegate. PMID- 8438123 TI - Lead still poisoning our children. PMID- 8438124 TI - What's wrong with this patient? Mike has Ehlers-Danlos syndrome. PMID- 8438125 TI - Second-degree AV block. PMID- 8438126 TI - What would you rather be doing? PMID- 8438128 TI - Suggest diets with a difference. PMID- 8438127 TI - Sexual harassment: an updated picture. PMID- 8438129 TI - RNs and the AMA. PMID- 8438130 TI - Don't overlook pain in AIDS patients. PMID- 8438131 TI - Hospital patients have a right to privacy. PMID- 8438132 TI - Clean intermittent catheterization--physical and psychological complications. AB - During a 6 months period in 1988, 407 patients (206 men and 201 women) with a mean age of 51.7 years, treated with clean intermittent catheterization (CIC), were included in a one-year prospective follow-up study regarding physical and psychological complications and complaints related to the treatment. According to diagnoses and examinations, the patients were divided in 5 groups: supranuclear affections (106 patients), infranuclear affections (141), detrusor myopathy (136), infravesical obstruction (19) and suprapontine affections (5). Significant bacteriuria was found in 50.6% of all urine samples analyzed, with E. Coli as the dominant species. In urine samples from patients not using antiinfective agents, bacteriuria was found in 57.5% while the corresponding figures in patients using methenamine hippurate and antibiotics were 42.5% and 37.5% respectively. Bacteriuria was found equally in both sexes. The distribution of species was equal in CIC-treated patients and in other outpatients studied. Only minor differences were found regarding the drug resistance pattern. The prevalence of symptomatic urinary tract infections varied from 11.9% to 17.4% with a higher frequency in females and patients using antibiotics. During the observation period of one year 24.5% had no clinical UTI at all, 58.6% had minor symptoms, 14.3% had more comprehensive or frequent symptoms while 2.6% claimed major symptoms. Women had a higher clinical infection rate than men (p < 0.01). Bleeding in connection with the catheterization procedure varied from 10.7% to 13.6%. Traces of blood were detected in 22.8% of all urine samples analyzed with no differences between patients who claimed observing blood and those denying. No other major physical complications were detected in significant values or seriousness. Predictive factors of clinical UTI were low age and high mean catheterization volume in female patients. In male patients low age, neurogenic bladder dysfunction and non-self-catheterization were predictors in addition to urine leakage in those with neurogenic dysfunction. Bacteriuria was a risk factor of future clinical infection and bacteriuria. No other risk factor of bacteriuria could be identified in the female population, while low frequency of catheterization, high age and non-self-catheterization were found predictive in males.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8438133 TI - [Tuberculosis 1992: current clinical aspects, epidemiology and diagnosis]. AB - We review four different aspects of tuberculosis (TB), a disease which is making a comeback as a focus of medical attention. The diagnosis of TB in HIV infected individuals can be very challenging for the clinician and an increased number of side effects complicates treatment. Updated information in this area appears necessary for physicians who are in charge of HIV-infected patients. The "cursed duet" of TB and HIV infection is also responsible for the increase of TB in subsaharan Africa. Recent data are discussed in relation to this issue. Another problem for developing countries is the diagnosis and treatment of children's TB, which involves particular features as compared to the adult form of the disease. Finally, new diagnostic methods are now available from the laboratory. The detection of mycobacteria with the polymerase chain reaction has proven very useful in the diagnosis of tuberculous meningitis. Detection of tuberculostearic acid and mycobacterial antigen also represent important advances. The role of these techniques in the diagnosis of TB forms other than meningitis will need to be defined in the near future. PMID- 8438134 TI - [Current methods in rapid diagnosis of tuberculosis]. AB - The field of mycobacteriology has significantly advanced during the past 10 years. Optimized specimen processing, fluorescence microscopy, radiometric mycobacterial detection system, and use of nucleic acid probes for identification provide more rapid and more sensitive detection of tuberculous mycobacteria. Nevertheless, the diagnosis of tuberculosis is often a long and tedious process which can take up to several weeks. Recently, several new and rapid diagnostic tests have been developed. Despite major advances, the serodiagnosis of tuberculosis remains an investigational method requiring further development and prospective evaluation. Detection of tuberculostearic acid in cerebrospinal fluid by use of gas chromatography-mass spectrometry has proven to be a very rapid, sensitive, and specific test for tuberculous meningitis. The most recent development is the use of polymerase chain reaction (PCR) for the detection of Mycobacterium tuberculosis directly in clinical specimens. PCR is an extremely sensitive and rapid method based on in vitro amplification of specific DNA sequences. However, before using this method for clinical practice, further efforts to develop simple routine procedures that are safe from cross contamination are warranted. Furthermore, large-scale trials are needed to determine the clinical value of diagnostic PCR assay for diagnosis of tuberculosis in different patient populations. PMID- 8438135 TI - [Is antitubercular chemoprophylaxis useful--a controversy]. PMID- 8438136 TI - [Indications for chemoprophylaxis of tuberculosis. Arguments for]. AB - After a first infection with M. tuberculosis, reactivation of the disease may be prevented by chemoprophylaxis with isoniazid or rifampicin. Such chemoprophylaxis should be administered to all subjects with an immune defect due to HIV infection, immunosuppressors, severe diabetes, renal insufficiency or silicosis. Extensive sequelae of tuberculosis on chest X-ray are also a major risk of reactivation without treatment. Tuberculosis is most likely to become active during the first three years following first infection for an healthy subject. However, beyond this limit or when the time of infection is unknown, the most objective decisional analysis still demonstrates the clear-cut benefit of chemoprophylaxis in proportion to its side effects for all young subjects aged less than 35 years. PMID- 8438137 TI - [Preventive chemotherapy for tuberculous infection. Arguments against]. AB - Preventive chemotherapy with isoniazid (INH) is generally considered to be indicated in some patients with tuberculous infection who have a high risk of evolution towards disease. There are, however, some practical problems of treatment which may limit its application: correct assessment of tuberculin tests and risk factors, monitoring of treatment, patient compliance and management of possible side effects. Current treatment may not yet represent the ideal solution. PMID- 8438138 TI - [Scuba diving: barotrauma, decompression sickness, pulmonary contra-indications]. AB - The practice of scuba diving is associated with two specific medical problems: barotrauma directly related to changes in ambient pressure, and decompression sickness related to the uptake and the release of inert gases by the body. Neurological symptoms are frequent in severe diving accidents. They may arise following either barotrauma or decompression sickness, and often require urgent treatment in a hyperbaric chamber. Asthma, chronic obstructive pulmonary disease, and spontaneous pneumothorax increase the risk of lung barotrauma and represent contraindications to diving. PMID- 8438139 TI - [Mortality due to chronic obstructive bronchopneumopathies]. AB - Many recent studies have drawn attention to the rise in chronic obstructive pulmonary disease (COPD) mortality. COPD is the fifth leading cause of death in developed countries. While the data in these studies do indeed suggest that there is a global rise in COPD mortality, the increase is chiefly confined to old COPD cohorts while mortality is falling in younger COPD cohorts. The trend is probably due to the beneficial effect of stabilization or decrease of the smoking habit in developed countries. Medical antismoking campaigns are starting to be successful. There are many factors predictive of survival in COPD. As a therapeutic approach, long-term oxygen therapy is the only treatment which has definitely been shown (by two well controlled studies) to radically improve survival in hypoxemic COPD patients. However, much indirect evidence suggests that bronchodilators or topical corticosteroids may favourably influence survival in these patients. Well controlled long-term studies on these treatments are urgently needed. In the meantime, COPD patients should benefit from these treatments and smoking should be actively discouraged, to alleviate the heavy burden of COPD morbidity and mortality. PMID- 8438140 TI - [Exertional asthma in Swiss top-ranking athletes]. AB - In 1990, 1530 active Swiss athletes of national or international level (53% response rate) answered a questionnaire on allergies, hay fever and respiratory symptoms during or after physical effort. Compared with 1986, the prevalence of allergies among these athletes had increased from 14.7 to 18%, and of hay fever from 16.8 to 19.7%. The prevalence of respiratory symptoms was 12.1 in 1990, compared with 7.1% in 1986. Smoking was less frequent than in 1986 (7.1% against 12%). There was a significant correlation between the reported allergies and respiratory symptoms, but none between respiratory symptoms and smoking or frequency of consultations at a physician's office. The examination of 104 athletes complaining of respiratory symptoms on 10 minutes ergometry showed a decrease of FEV1 of 10% or more in 21%. Exercise induced asthma (EIA) is not as frequent as suspected in other publications. 25% of the sportsmen examined showed a cutaneous allergy to one or more of the six most frequent inhalative allergens. The typical history of dyspnea, wheezing or coughing after exercise, possibly combined with a feeling of tightness of the chest or the larynx, and the number of positive allergy skin test reactions, correlated with the decrease in FEV1 after exercise. A considerable percentage of these athletes do not treat their respiratory symptoms or ask for professional help. In medical treatment, attention must be paid to doping regulations. IOC accepts the use of salbutamol, terbutaline, orciprenaline and Cromoglycic acid in the treatment of asthma. Corticosteroids by inhalation are accepted but intramuscular injection is forbidden.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8438141 TI - [Air pollution]. AB - This review includes a summary of the symposium "Air Pollution" of the Swiss Society of Pneumology, and supplementary information on in- and outdoor air quality in Switzerland. With regard to atmospheric pollution, high exposures to ozone during summer are of major concern. A substantial reduction of ozone levels appears to be considerable problem in view of the high population and particular topography. More precise estimates of possible health damage require further epidemiological studies. In this context it is interesting to note that the environmental catastrophe of Kuwait did not reveal new insights into the dose effect relation of air pollutants, in that the exposure of the population and hence the health hazards of oil fires were less serious than expected. As to the wellbeing of humans, indoor air pollution deserves equal attention. The predominant noxious agent is tobacco smoke, which significantly affects the respiratory health of infants. In addition, there is some epidemiological evidence that passive smoking can cause lung cancer. However, a variety of other and often neglected pollutants can be present in homes and at workplaces and may be the cause of various respiratory diseases. Finally, thought is given to more general problems such as better definitions and diagnosis of diseases due to airborne agents, the cost-benefit ratio and the conflicts of interest involved in effective control measures. PMID- 8438142 TI - [Air pollution and the juvenile lungs]. AB - The present overview summarizes data from the literature dealing with effects of air pollution on lung health in children. Special care was taken to critically review manuscripts which were published in peer reviewed international journals. In doing so, one realizes that the degree of air pollution is closely related to pulmonary problems of children. However, since single peak loads of polluted air might not be a sufficient indicator for long-term effects of contaminated air on human health, special care has to be taken to search for connections between air toxicity and data of epidemiology, physiology, and pathophysiology. PMID- 8438143 TI - [Polysomnography: useful or superfluous?]. AB - The sleep apnea/hypopnea syndrome is a common disorder. Medical and social complications are frequent. When the condition is untreated, life expectancy is reduced. The standard technique for diagnosing sleep apnea and establishing effective long-term treatment is overnight polysomnography. Limited diagnostic investigations and screening methods are currently being investigated. PMID- 8438144 TI - Environmental aspects of pesticide use in Italian agriculture. AB - Pesticides used in agriculture accumulate in organisms and reach man through complex metabolic pathways. Accurate analysis of pesticides presence in each step of the food chain is necessary because of the high number of these substances, their potential toxicity and the presence of amplified toxic effects due to synergic interactions. In the same way it is necessary to evaluate the environmental effects of the whole pesticides cycle, from industrial production until final disposal of used containers and residuals. Furthermore recent introduction of new categories of chemicals which are not strictly classifiable as pesticides (photosynthetic activity stimulators, aesthetic aspect enhancers) and not yet sufficiently studied in their metabolic behaviour, increase the problem complexity. Complete studies about these complex problems and about the effects on ecosystems have not yet been carried out in Italy, due to ambiguous laws and regulations, inadequate data collection methods and decisional influence of the chemical industry on agriculture policy. PMID- 8438145 TI - Correction: a Li-Fraumeni syndrome p53 mutation. PMID- 8438146 TI - Hughes' tough stand on industry ties. PMID- 8438147 TI - A shot in the arm for TB research. PMID- 8438148 TI - AIDS research. Shalala backs reorganization. PMID- 8438149 TI - Scripps-Sandoz deal comes under fire. PMID- 8438150 TI - Unexpected intelligence turns up in a cellular gel. PMID- 8438151 TI - Cell communication failure leads to immune disorder. PMID- 8438152 TI - Cloning the differences between two complex genomes. AB - The analysis of the differences between two complex genomes holds promise for the discovery of infectious agents and probes useful for genetic studies. A system was developed in which subtractive and kinetic enrichment was used to purify restriction endonuclease fragments present in one population of DNA fragments but not in another. Application of this method to DNA populations of reduced complexity ("representations") resulted in the isolation of probes to viral genomes present as single copies in human DNA, and probes that detect polymorphisms between two individuals. In principle, this system, called representational difference analysis (RDA), may also be used for isolating probes linked to sites of genomic rearrangements, whether occurring spontaneously and resulting in genetic disorders or cancer, or programmed during differentiation and development. PMID- 8438153 TI - Existence of a flat phase in red cell membrane skeletons. AB - Biomolecular membranes display rich statistical mechanical behavior. They are classified as liquid in the absence of shear elasticity in the plane of the membrane and tethered (solid) when the neighboring molecules or subunits are connected and the membranes exhibit solid-like elastic behavior in the plane of the membrane. The spectrin skeleton of red blood cells was studied as a model tethered membrane. The static structure factor of the skeletons, measured by small-angle x-ray and light scattering, was fitted with a structure factor predicted with a model calculation. The model describes tethered membrane sheets with free edges in a flat phase, which is a locally rough but globally flat membrane configuration. The fit was good for large scattering vectors. The membrane roughness exponent, zeta, defined through h alpha L zeta, where h is the average amplitude of out-of-plane fluctuations and L is the linear membrane dimension, was determined to be 0.65 +/- 0.10. Computer simulations of model red blood cell skeletons also showed this flat phase. The value for the roughness exponent, which was determined from the scaling properties of membranes of different sizes, was consistent with that from the experiments. PMID- 8438154 TI - The secretory granule matrix: a fast-acting smart polymer. AB - The secretory granule matrix is a miniature biopolymer that consists of a charged polymer network that traps peptides and transmitters when it condenses and releases them on exocytotic decondensation. Models of exocytotic fusion have treated this matrix as a short circuit and have neglected its electrical contributions. This matrix responded to negative voltages by swelling, which was accompanied by a large increase in conductance, and to positive voltages by condensing. Thus, the matrix resembled a diode. The swollen matrix exerted large pressures on the order of 12 bar. The responses took place within milliseconds of the application of the electric field. These findings suggest that matrix decondensation, and therefore product release, is controlled by potential gradients. PMID- 8438155 TI - Structure of the thiamine- and flavin-dependent enzyme pyruvate oxidase. AB - Pyruvate oxidase from Lactobacillus plantarum is a tetrameric enzyme that decarboxylates pyruvate, producing hydrogen peroxide and the energy-storage metabolite acetylphosphate. Structure determination at 2.1 angstroms showed that the cofactors thiamine pyrophosphate (TPP) and flavin adenine dinucleotide (FAD) are bound at the carboxyl termini of six-stranded parallel beta sheets. The pyrophosphate moiety of TPP is bound to a metal ion and to a beta alpha alpha beta unit corresponding to an established sequence fingerprint. The spatial arrangement of TPP and FAD suggests that the oxidation of the oxyethyl intermediate does not occur by hydride displacement but rather by a two-step transfer of two electrons. PMID- 8438156 TI - Deletion of IRF-1, mapping to chromosome 5q31.1, in human leukemia and preleukemic myelodysplasia. AB - One of the most frequent cytogenetic abnormalities in human leukemia and myelodysplasia is an interstitial deletion within chromosome 5q. A tumor suppressor gene has been hypothesized to lie in 5q31, the smallest commonly deleted region. IRF-1, a gene whose product manifests anti-oncogenic activity, was mapped to 5q31.1. IRF-1 lies between IL-5 and CDC25C and is centromeric to IL 3 and GM-CSF. Among these genes, only IRF-1 was consistently deleted at one or both alleles in 13 cases of leukemia or myelodysplasia with aberrations of 5q31. Inactivating rearrangements of one IRF-1 allele, accompanied by deletion of the second allele, were also identified in one case of acute leukemia. Thus, IRF-1 may be a critically deleted gene in human leukemia and myelodysplasia. PMID- 8438157 TI - Anti-oncogenic and oncogenic potentials of interferon regulatory factors-1 and 2. AB - Interferon regulatory factor-1 (IRF-1), a transcriptional activator, and IRF-2, its antagonistic repressor, have been identified as regulators of type I interferon and interferon-inducible genes. The IRF-1 gene is itself interferon inducible and hence may be one of the target genes critical for interferon action. When the IRF-2 gene was overexpressed in NIH 3T3 cells, the cells became transformed and displayed enhanced tumorigenicity in nude mice. This transformed phenotype was reversed by concomitant overexpression of the IRF-1 gene. Thus, restrained cell growth depends on a balance between these two mutually antagonistic transcription factors. PMID- 8438159 TI - Shutdown of class switch recombination by deletion of a switch region control element. AB - Upon activation, B lymphocytes can change the class of the antibody they express by immunoglobulin class switch recombination. Cytokines can direct this recombination to distinct classes by the specific activation of repetitive recombinogenic DNA sequences, the switch regions. Recombination to a particular switch region (s gamma 1) was abolished in mice that were altered to lack sequences that are 5' to the s gamma 1 region. This result directly implicates the functional importance of 5' switch region flanking sequences in the control of class switch recombination. Mutant mice exhibit a selective agammaglobulinemia and may be useful in the assessment of the biological importance of immunoglobulin G1. PMID- 8438158 TI - Carboxyl methylation of Ras-related proteins during signal transduction in neutrophils. AB - In human neutrophils, as in other cell types, Ras-related guanosine triphosphate binding proteins are directed toward their regulatory targets in membranes by a series of posttranslational modifications that include methyl esterification of a carboxyl-terminal prenylcysteine residue. In intact cells and in a reconstituted in vitro system, the amount of carboxyl methylation of Ras-related proteins increased in response to the chemoattractant N-formyl-methionyl-leucyl phenylalanine (FMLP). Activation of Ras-related proteins by guanosine-5'-O-(3 thiotriphosphate) had a similar effect and induced translocation of p22rac2 from cytosol to plasma membrane. Inhibitors of prenylcysteine carboxyl methylation effectively blocked neutrophil responses to FMLP. These findings suggest a direct link between receptor-mediated signal transduction and the carboxyl methylation of Ras-related proteins. PMID- 8438160 TI - Minorities in science: the dialogue. PMID- 8438161 TI - A 'Manhattan project' for AIDS? PMID- 8438162 TI - Pasteur notebooks reveal deception. PMID- 8438163 TI - Deja vu guides the way to new antimicrobial steroid. PMID- 8438164 TI - A complete second gut induced by transplanted micromeres in the sea urchin embryo. AB - Founder cells for most early lineages of the sea urchin embryo are probably specified through inductive intercellular interactions. It is shown here that a complete respecification of cell fate occurs when 16-cell stage micromeres from the vegetal pole of a donor embryo are implanted into the animal pole of an intact recipient embryo. Animal pole cells adjacent to the transplanted micromeres are respecified from presumptive ectoderm into vegetal plate founder cells. These induced vegetal plate cells express the entire battery of genes characteristic of the endogenous vegetal plate cells. The ectopic vegetal plate invaginates during gastrulation to form a second archenteron which differentiates properly into a tripartite gut, as shown by the spatial pattern of expression of an endoderm-specific marker gene. Thus, transplanted micromeres can signal neighboring cells to induce them to change their fate. PMID- 8438165 TI - The nonhelical structure of antifreeze protein type III. AB - Antifreeze proteins (AFPs) are present in the blood of some marine fishes and inhibit the growth of ice crystals at subzero temperatures by adsorption to the ice lattice. The solution structure of a Type III AFP was determined by two dimensional nuclear magnetic resonance spectroscopy. These measurements indicate that this 66-residue protein has an unusual fold in which eight beta strands form two sheets of three antiparallel strands and one sheet of two antiparallel strands, and the triple-stranded sheets are packed orthogonally into a beta sandwich. This structure is completely different from the amphipathic, helical structure observed for Type I AFPs. PMID- 8438166 TI - Identification of a ten-amino acid proline-rich SH3 binding site. AB - The Src homology 3 (SH3) region is a small protein domain present in a very large group of proteins, including cytoskeletal elements and signaling proteins. It is believed that SH3 domains serve as modules that mediate protein-protein associations and, along with Src homology 2 (SH2) domains, regulate cytoplasmic signaling. The SH3 binding sites of two SH3 binding proteins were localized to a nine- or ten-amino acid stretch very rich in proline residues. Similar SH3 binding motifs exist in the formins, proteins that function in pattern formation in embryonic limbs of the mouse, and one subtype of the muscarinic acetylcholine receptor. Identification of the SH3 binding site provides a basis for understanding the interaction between the SH3 domains and their targets. PMID- 8438167 TI - A functional role for GTP-binding proteins in synaptic vesicle cycling. AB - The squid giant synapse was used to test the hypothesis that guanosine-5' triphosphate (GTP)-binding proteins regulate the local distribution of synaptic vesicles within nerve terminals. Presynaptic injection of the nonhydrolyzable GTP analog GTP gamma S irreversibly inhibited neurotransmitter release without changing either the size of the calcium signals produced by presynaptic action potentials or the number of synaptic vesicles docked at presynaptic active zones. Neurotransmitter release was also inhibited by injection of the nonhydrolyzable guanosine diphosphate (GDP) analog GDP beta S but not by injection of AIF4-. These results suggest that a small molecular weight GTP-binding protein directs the docking of synaptic vesicles that occurs before calcium-dependent neurotransmitter release. Depletion of undocked synaptic vesicles by GTP gamma S indicates that additional GTP-binding proteins function in the terminal at other steps responsible for synaptic vesicle replenishment. PMID- 8438168 TI - [Results of a combined surgical procedure in complete Tossy III acromioclavicular joint dislocation]. AB - This paper presents the results of a follow-up examination of 31 patients who had undergone reconstructive surgery for complete acromioclavicular (AC) dislocation between 1 September 1986 and 30 June 1989. The operation performed consisted in suturing of coracoclavicular and acromioclavicular ligaments with a coracoclavicular PDS cord augmentation and a transarticular K-wire left in place for 6 weeks. The follow-up investigation included a questionnaire on subjective assessment and daily problems with the treated shoulder, a clinical examination and a X-ray of both shoulders with 10 kg weight on each side. Good and very good results were found in 93% for clinical patterns, in 90% for subjective opinion, and in 79% for radiological examination. No correlation could be found between clinical results and radiological results, even concerning AC joint arthrosis following the operation. PMID- 8438169 TI - [Surgical treatment of Galeazzi fracture]. AB - In this study 20 patients with Galeazzi fractures were studied. In 19 patients the Galeazzi fracture was reset using the osteosynthetic procedure and one had conservative treatment alone. Open repositioning is apparently unavoidable. The fracture should be treated with dynamic compression plates (DCP) using 6-8 holes. It is also still open to question as to whether a prolonged healing process can be avoided. A revision of the wrist should only be done if the stability after osteosynthesis is not guaranteed or if repositioning is not satisfactory. Post operative immobilization proved to be of no value. Although with improved operative techniques the prognosis is not bad, subluxation persists. PMID- 8438170 TI - [Surgical treatment of habitual patella dislocations by combined soft tissue surgery]. AB - Since January 1988 21 operations using a modified Madigan and Goldthwait method have been carried out on 18 patients suffering from recurrent dislocation of the patella. This soft tissue procedure is presented here in its individual operational steps. The average age of the patients was 22 years and the majority were female (6:1). The mean follow-up time was 19.3 months. One patient who had both knees operated on reported recurrent luxation 6 months after the operation in one knee and subluxation in the other. None of the other patients suffered further dislocations. In the opinion of the patients, 17 (81%) knee operations were evaluated as favorable (good/very good, satisfactory) while 4 (19%) were considered unsatisfactory. All patients had stable knee joints and a full range of motion. The modified soft tissue operation presented here can be recommended for all patients with recurring patella dislocations if previous conservative functional therapy remains unsuccessful. PMID- 8438171 TI - [Percutaneous bone biopsy. Critical analysis of 153 patients]. AB - The value of transcutaneous bone biopsy was critically examined in a retrospective study of 153 patients with various bone diseases. A comparison of the clinical, radiological and histological findings gave reliable results in approximately 82%. Specific results were worse in inflammatory processes than in those involving tumours. The results of biopsy were of particular interest where clinical and radiological examinations pointed to an isolated bone metastasis in cases of known and unknown primary tumours. The advantages of the method are discussed with regard to the patient's well-being and to cost. PMID- 8438172 TI - [Development of aneurysma spurium of the arteria profunda femoris as a late complication of DHS osteosynthesis]. AB - A rare case of a false aneurysm of the profunda femoris artery as a late iatrogenic complication of dynamic hip screw osteosynthesis is described. A review of complications of the dynamic hip screw and other means of internal fixation is given, with special reference to arterial injury during trauma surgery. PMID- 8438173 TI - [Mechanoreceptors in the distal aspects of the m. vastus medialis?]. AB - Five cadavers were fixed in Jores' solution and alcohol. The distal parts of the medial vastus muscle and the medial parts of the patella ligament and of the capsule of the knee joint were prepared and histologically examined. Previous examinations had shown mechanoreceptors in the knee joint ligaments; the present study was designed to find whether mechanoreceptors could be identified in the anatomical structures mentioned, in which case an arthrotomy by the Payr access would interrupt the muscle reflexes. Only some mechanoreceptors in the medioventral parts of the knee joint capsule close to the tendon of the great muscle could be identified. Thus, when the Payr access is used there is no interruption of the sensibility transmitted by proprioceptors. PMID- 8438174 TI - [Two cases of complex carpometacarpal dislocation]. AB - Dislocations and fracture dislocations of the carpometacarpal joints are rare. In most cases they are caused by sudden forces, e.g. the crash of a motorcyclist against an obstacle while holding the handlebars or direct compression of the hand by a machine. The majority of patients are male. The literature contains reports of dorsal, palmar and divergent dislocations involving anything from one to all five carpometacarpal joints. Since the numbers of cases published by the various authors are rather small and different methods of treatment are proposed, we would like to describe two more carpometacarpal dislocations and compare them with previous reports. PMID- 8438175 TI - [Importance of ultrasound in postoperative follow-up after reconstruction of the anterior cruciate ligament]. AB - Eighty-eight male patients following reconstruction of the anterior cruciate ligament (ACL; mean 24 months since operation) had a thorough clinical examination including instrumented measurement of laxity using the KT 1000. These results were correlated with an ultrasound (US) grading that evaluates the reconstruction itself as well as its functional behaviour during the anterior drawer test. Thirty-four magnetic resonance (MR) studies of 33 patients were available. Undoubtedly postoperative visualization of the reconstructed ACL is superior to that of both normal control ACL and acute trauma cases. Especially operative procedures which use the patellar or semitendinosus tendon lend themselves to accurate evaluation of the intraarticular reconstruction. The sensitivity, specificity, positive and negative predictive values and overall accuracy of US/MR versus the clinical laxity measurement are calculated to be 66.7%/96.0%, 71.2%%/23.8%, 59.5%/60.0%, 77.1%/83.3% and 69.4%/63.0% respectively. US has a satisfactory diagnostic value and performs similarly well on all these parameters. MR, on the other hand, correctly diagnoses nearly all unstable knees but is associated with a high number of false positives. There is no statistically significant, linear correlation between MR and US; r = -0.0769, P = 0.6706. Only three times did the reconstructed ACL appear normal on MR, whereas 48.5% of the reconstructions were graded type I (normal) on US. Clinical Consequences: Ultrasound and MRT should not be considered rival but rather complementary methods: ultrasound is a good method for documenting changes within the knee joint on an outpatient basis, while the indications for MR in the postoperative course are any occurrences of pain, instability or reinjury. PMID- 8438176 TI - [Comminuted open tibial fracture. An alternative treatment method]. AB - The treatment of comminuted fracture of the tibia is one of the problem cases in operative fracture care. In our department we favour stabilization with the aid of interlocking nails, providing absolute fixation of the interlocking screw is possible. The patient is positioned on the Maquet table, and the fracture of the tibia is temporarily reduced by the Goetze percutaneous cerclage wiring technique. The special feature of our method is that we remove the wires after nailing. In this way the advantages of both techniques, anatomical reduction with cerclage wires and the stability and possibility of early mobilization afforded by interlocking nailing are combined. Poor blood flow in the periosteum is avoided by the immediate removal of the wires. PMID- 8438177 TI - [Osteosynthesis using a buttress plate--a new principle for stabilizing scaphoid pseudarthroses]. AB - Deformity with palmar bone resorption can be observed in 20-50% of scaphoid pseudarthroses. A palmar wedge-shaped defect develops after repositioning and debridement of the pseudarthrosis. In the present paper 16 cases in which operations with cancellous bone grafting and palmar buttress plate osteosynthesis in addition were performed are presented. In all but 1, the pseudarthrosis united. All patients were pain-free at follow-up examination a minimum of 9 months (mean 28 months) only slightly reduced. Grip strength and mobility were after operation. The persisting pseudarthrosis necessitated wrist arthrodesis because of radiocarpal arthrosis. Metal slackening with erosion and rupture of the flexor pollicis longus tendon occurred in 1 patient. Palmar buttress plating is a biomechanically consistent form of osteosynthesis. It neutralizes all relevant forces. This means that cancellous bone grafts are sufficient, whereas lag screw or tension band osteosyntheses need cortico-cancellous grafts to resist compression forces. Stability and better chances of healing of pure cancellous bone grafts are the main advantages of palmar buttress plating in scaphoid pseudarthroses. PMID- 8438178 TI - Inferior subluxation of the shoulder. PMID- 8438179 TI - Subluxation of the upper thoracic spine in rheumatoid arthritis. AB - Only single cases with rheumatoid arthritis of the thoracic spine with vertebral subluxation have been reported to date. In a review of 100 patients with severe rheumatoid arthritis who had undergone occipitocervical fusion, arthritis of the upper thoracic spine with subluxation was discovered on conventional radiographs in four patients. Two additional patients were found elsewhere. Magnetic resonance imaging (MRI) was performed in three of the patients, confirming the diagnosis of subluxation of the upper thoracic vertebrae. In addition, MRI revealed encroachment on the anterior subarachnoid space and compression of the spinal cord. PMID- 8438180 TI - Bone mineral and other bone components in vertebrae evaluated by QCT and MRI. AB - To evaluate the usefulness of assessing bone components using magnetic resonance imaging (MRI), the contributions of bone components, including mineral, fat and collagen, to bone mineral density (BMD) and T1 relaxation time (T1) were studied using phantoms. Excised human vertebrae were also evaluated by quantitative computed tomography (QCT) and MRI. T1 was shortened with increasing quantities of fat and collagen. In water, T1 was significantly affected by bone density, while in oil, T1 became slightly longer as bone density increased. The presence of fat and collagen caused under- and overestimations of BMD, respectively. There was good correlation between T1 and BMD in osteoporotic vertebrae and the vertebrae with long T1 showed an increased content of hematopoietic marrow and/or abnormally increased bone mineral. It was concluded that the experimental data showed that MRI can contribute to the assessment of bone quality. PMID- 8438181 TI - The periphysis and its effect on the metaphysis. II. Application to rickets and other abnormalities. AB - The metaphyseal collar due to the periphysis is lost (in 98% of 49 subjects) as an early sign of rickets and returns with recovery. The term "pseudophysis" refers to that unossified metaphyseal osteoid and cartilage as in rickets. The collar is intact in metaphyseal chondrodysplasias (a helpful sign in differential diagnosis from rickets), is shortened in achondroplasia, and frequently is spared in osteomyelitis, luetic bone disease, and Caffey infantile cortical hyperostosis. The periphyseal bone bark is thinned, but often apparent, in rickets, and is not thinned in cases of tyrosinosis and phenylketonuria. PMID- 8438182 TI - Elastofibroma dorsi: a radiological diagnosis. AB - Elastofibroma dorsi is a rarely made radiological diagnosis. The rarity of the condition, lack of a suitable imaging modality, and an inconsistent clinical approach in evaluating indeterminate soft tissue tumors has contributed to this failure. With magnetic resonance imaging now being recognized as the examination of choice for all indeterminate soft tissue tumors, a prebiopsy diagnosis can frequently be made by radiologists familiar with the characteristic periscapular location, predilection for elderly females, and short T2 on magnetic resonance imaging. PMID- 8438183 TI - Case report 758. Reflex sympathetic dystrophy syndrome (RSDS). AB - We report the angiographic and venographic findings in a case of reflex sympathetic dystrophy syndrome (RSDS) of the lower extremity. The hypervascular intraosseous lesion which initially simulated an arteriovenous malformation provides important information about the vascular nature of this lesion. PMID- 8438184 TI - Case report 772. Stress fracture of the hip secondary to renal osteodystrophy and erosion of ischium due to amyloid deposition. AB - We have reported the case history of a 72-year-old woman who was on hemodialysis for 15 years. Her course was marked by many of the musculoskeletal complications of ESRD including CTS, stromal amyloid deposition of synovium, amyloid cystic degeneration of bone, and inflammation of the synovium due to the deposition of calcium oxalate and calcium pyrophosphate microcrystals. She also had evidence of metabolic bone disease: moderate osteoporosis related to secondary hyperparathyroidism and osteomalacia related to aluminum deposition at the mineralization front. The pathological and radiological findings associated with her bone disease are described. PMID- 8438185 TI - Case report 774. Coincidental parosteal lipoma with osseous excresence and intramuscular lipoma. AB - The parosteal lipoma is a rare but recognizable lesion. The combination of (a) a well-defined, radiolucent, soft-tissue mass that on CT is confirmed to be entirely composed of homogenous mature adipose tissue and (b) an osseous excresence and/or saucerization at the attachment of the soft-tissue mass to the subjacent cortex should be diagnostic. We were unable to find any other case report of a parosteal lipoma coexisting with another lipoma in the same individual. PMID- 8438186 TI - Case report 775. Canine osteosarcoma with associated avascular necrosis and sequestrum formation. AB - A young dog was found to have an osteosarcoma of the proximal femur containing a radiologically evident sequestrum of dead bone. Although the tumor was extensive, the plain films were most remarkable for the presence of a sequestrum. MR scans revealed the extent of the lesion, with low signal throughout the lesion consistent with the heavily calcified tumor and central avascular bone. At the 1 year follow-up, lung metastases had developed, but the dog appeared well. PMID- 8438187 TI - MRI of soft tissue tumors. AB - Magnetic resonance imaging (MRI) is the only noninvasive method of defining a soft tissue tumor. The extent of the tumor and the question of involvement or noninvolvement of various adjacent tissues and structures can be determined. This information, determination of lymphatic and distant metastatic spread, is invaluable for staging and management of the disease. Whether or not the tumor type can be reliably determined, or even whether the malignant or benign nature of the tumor can be ascertained on MRI examination, is open to question. Review of the literature indicates proponents on both sides of the issue. This review illustrates the imaging features that are relevant to suggesting a histologic diagnosis, and the pitfalls that are encountered in trying to determine the malignancy or benignity of a lesion. The clinical significance of these determinations is also discussed. PMID- 8438188 TI - Anterior cervical spine fusion: struts, plugs, and plates. AB - Bone grafting in the cervical spine is an expanding and rapidly changing area. Its success depends on the presence of bone formation, bone incorporation, and ongoing adaptive remodeling to mechanical loads. The evaluation of anterior cervical spine grafts requires a basic understanding of bone graft physiology, its clinical applications, and its postoperative appearances. The roles of routine radiography, polydirectional tomography, computed tomography, and magnetic resonance imaging in the assessment and follow-up of the postoperatively grafted cervical spine will be discussed. The main focus of this paper is to review current surgical procedures utilized for stabilizing the cervical spine as well as to discuss the radiologist's role in the imaging of this region. PMID- 8438189 TI - Hematopoietic bone marrow in the adult knee: spin-echo and opposed-phase gradient echo MR imaging. AB - Hematopoietic bone marrow in the distal femur of the adult may be mistaken for a pathologic marrow process in magnetic resonance imaging of the knee. We investigated the incidence of hematopoietic marrow in the distal femur in a series of 51 adult patients and compared spin-echo (TR/TE in ms: 500/35, 2000/80) and opposed-phase gradient-echo (0.35 T, TR/TE in ms: 1000/30, theta = 75 degrees) magnetic resonance images. Zones with intermediate to low signal intensity on T1-weighted spin-echo and opposed-phase gradient-echo sequences representing hematopoietic marrow within high signal intensity fatty marrow were observed in 18 of the 51 patients. Five patterns of marrow signal reduction were identified; type 0: uniform high signal, i.e., no signal change; type I, focal signal loss; type II, multifocal signal loss without confluence; type III, confluent signal loss; and type IV, complete homogeneous reduction in marrow signal. Opposed-phase gradient-echo sequences demonstrated markedly greater red yellow marrow contrast than conventional spin-echo sequences. Follow-up studies in three patients using a gradient-echo sequence with TE varying from 10 to 21 ms at 1-ms increments showed a cyclic increase and decrease in red and yellow marrow signal intensity depending on the TE. The contribution of intravoxel chemical shift effects on red-yellow marrow contrast in opposed-phase gradient-echo images was verified by almost complete cancellation of the TE-dependent marrow signal oscillation with use of a chemically selective pulse presaturating the water protons. Hematopoietic marrow in the adult distal femur in the absence of hematologic abnormalities is found primarily in women of menstruating age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8438190 TI - Preoperative irradiation for unresectable carcinoma of the rectum. AB - The records of 20 patients with unresectable carcinoma of the rectum who received preoperative radiation therapy (4,300 to 5,580 cGy) in an attempt to facilitate resection were reviewed. Patients were stratified as unequivocally unresectable at the time of diagnosis or borderline resectable. Thirteen of the 20 patients were able to undergo resection with curative intent after radiotherapy. Patients had follow-up examinations for a minimum of five years, and median survival period for all patients was 43 months with a five year survival rate of 40 percent. Patients stratified to unequivocally resectable survived for a median of only 17 months. Three of the 13 patients who underwent a curative resection had a local recurrence in the pelvic area. Sixteen complications occurred in nine of the 17 patients who underwent any sort of resection, with infectious and wound healing complications being most prevalent. The incidence of complications in similar series is discussed and the need for better selection of patients is addressed. PMID- 8438191 TI - The role of abdominal metroplasty in the era of operative hysteroscopy. AB - The current retrospective study was undertaken at a tertiary care academic reproductive medical center to evaluate the role of abdominal metroplasty (Jones or Strassman techniques) in patients with bicornuate uteri, T-shaped uteri and septate uteri when associated with other pelvic lesions not amenable to the transcervical approach. Fifteen patients with double uterus (13 septate and two bicornuate) and three with T-shaped uterine cavities after diethylstilbestrol exposure underwent abdominal metroplasty (Jones or Strassman techniques) for the repair of the uterus during the period August 1983 through August 1991. Patients with septate uteri had other pelvic lesions as well. Thirteen of 16 patients attempting pregnancy conceived and delivered postoperatively. The fetal wastage rate decreased from 87.9 percent before metroplasty to 9.1 percent after metroplasty. Abdominal metroplasty (Jones or Strassman techniques) continues to yield gratifying results in patients with bicornuate, T-shaped and septate uteri. When patients have additional pelvic lesions not amenable to the transcervical approach alone, it may be appropriate to use conventional abdominal metroplasty. For the bicornuate condition, this remains the only approach. PMID- 8438192 TI - The impact of operative bleeding on outcome in transplantation of the liver. AB - Excessive operative blood transfusion has been correlated with an increased rate of infectious complications and lower survival rate after transplantation of the liver. Two hundred and five consecutive transplants of the liver, performed between January 1988 and December 1989, were studied retrospectively to determine preoperative risk factors associated with an increased operative blood loss and to evaluate the impact of operative transfusion on the outcome of transplantation. Preoperative clinical and laboratory parameters in patients who required 10 units or more of banked erythrocytes were compared with those in patients who received less than ten units of erythrocytes. In evaluating the outcome, the two groups were compared for infection, rejection and graft and patient survival rates. The median operative blood loss for 205 patients was 5 units of banked erythrocytes (range of zero to 52, mean of 6.9 units). Only 41 patients (20 percent) required 10 units or more of erythrocytes. The significant factors on univariate analysis that were associated with an increased operative blood loss were hospitalized patients (United Network for Organ Sharing Status > or = 3), fulminant hepatic failure, previous portosystemic shunt and complete ABO mismatch. Patients who required more blood had higher incidence of coagulation abnormalities, renal dysfunction and high bilirubin levels. A stepwise logistic regression analysis model using all these parameters identified an elevated serum creatinine, decreased platelets and a prolonged partial thromboplastin time as being the strongest risk factors. Using these variables, operative bleeding of more than 10 units could be predicted accurately only 60 percent of the time (sensitivity 60.0 percent with a specificity of 69.1 percent). Septic episodes occurred more frequently in patients with an excessive operative blood loss (p < 0.05), and these patients also tended to have a higher rate of severe cytomegalovirus infections and a lower incidence of acute rejection. Patients who required more blood also had significantly prolonged stays in the intensive care units postoperatively (18.3 versus 6.3 days, p < 0.002) and lower graft and patient survival rates (p < 0.001 and p < 0.05, respectively). We conclude that intraoperative bleeding has remained a significant problem affecting the immediate outcome after transplantation of the liver. Preoperative parameters cannot predict operative bleeding accurately and the mainstay to prevent bleeding is a meticulous surgical technique during the hepatectomy and correction of coagulation abnormalities throughout the procedure. PMID- 8438193 TI - An evaluation of risk factors in incisional hernia recurrence. AB - In the present study, generally accepted risk factors for developing a primary incisional hernia are reviewed for their influence on the development of recurrent incisional hernia. The records of 417 patients undergoing an incisional hernia repair between 1980 and 1989 at the University Hospital Rotterdam were reviewed retrospectively, and in the event no hernia recurrence was documented, patients were asked to visit the outpatient department for physical examination. Patients having a primary incisional hernia (n = 302) were selected and patient related factors of gender, age, obesity, chronic cough, prostatism, constipation, diabetes mellitus and the use of corticosteroids were analyzed. In addition, operation related factors, including the technique of operation (mainly, one layer interrupted and one layer continuous closures), use of drains, use of antibiotics, wound contamination (fecal or purulent spill), duration of operation, technique of anesthesia, wound complications, mortality and period of hospitalization, were analyzed. Hernia related factors--the hernia-free interval, original operation, type of incision and the size of the hernias--were also analyzed. Statistical analysis of the data was performed using the chi-square test to compare percentages between groups. Cumulative percentages of patients having a recurrence along time were calculated using life-table methods. Of the group of primary incisional hernias, four patients lacked follow-up evaluation and were excluded, leaving 298 patients for study. With a mean follow-up period of 34.9 months, the recurrence rate was 36 percent; 45 percent had recurrence in the first year, 64 percent in the second year and 78 percent of all recurrences occurred within three years. Therefore, a follow-up evaluation of at least three years is recommended. The cumulative (life-table) recurrence rate after five years was 41 percent. After second, third and fourth incisional hernial repair, recurrence rates were higher (56, 48 and 47 percent, respectively). Except for the size of the hernia, none of the studied parameters led to a significantly higher recurrence rate. Obesity, diabetes mellitus, lower midline incision and wound infection did have higher recurrence rates, but these were not significant. Incisional hernias, smaller than 4 centimeters, had a significantly (p = 0.01) lower recurrence rate (25 percent) than larger hernias (41 percent). Considering these facts, a better technique is badly needed. In large defects, the use of inlay of prosthetic material consistently has the lowest recurrence rates. The question remains whether or not prosthetic material is also needed for repair of smaller hernias. PMID- 8438194 TI - Blood lost and transfused in patients undergoing elective orthopedic operation. AB - Autologous blood predeposit is a widely used transfusion practice that has become a standard of care for elective orthopedic operation. Despite the support for this practice, there are limitations in the use and efficacy of autologous blood programs. This study is a prospective analysis of 385 orthopedic patients in whom a type and crossmatch were requested in which 249 patients predonated autologous blood and 136 patients did not. Preoperative anemia, blood lost and the "transfusion trigger" were evaluated for each of these patients. We conclude that the prevalence of anemia (25 percent) and rate of homologous blood exposure (25 percent) in autologous blood donors indicate a need for innovative blood conservation strategies to minimize homologous blood transfusion in this patient subgroup; the high prevalence of anemia (39 percent) and the homologous blood exposure (49 percent) in patients who did not donate autologous blood demonstrate a need for early recognition and treatment to procure autologous blood and reduce homologous blood exposure in these patients. The procurement of three to eight autologous blood units, along with the regeneration of a erythrocyte volume of 8 to 12 milliliters per kilogram, would avoid homologous blood transfusion in 95 percent of the patients in this setting. PMID- 8438195 TI - Experience in twenty patients with carcinoma of hilar bile duct treated by resection, targeting chemotherapy and intracavitary irradiation. AB - Three years ago, we reported a new treatment modality for carcinoma of the hilar bile duct consisting of limited hepatic hilar resection with selective adjuvant therapies by local chemotherapy using a new drug delivery system and by intracavitary 60Co irradiation using a remote after loading system. This treatment was applied in 20 patients by April 1991 and the results are fairly good. The overall one, three and five year survival rates are 80, 33 and 26 percent, respectively, which are better than those reported. No serious complications have been observed after operation and adjuvant therapies. Comparing the survival rate and prognostic factors, it was proved that the prognostic factors were not influential in the 20 patients. For the further improvement of this treatment modality, some special devices will be necessary to treat not only the resection stump but also the excisional surface of the tumor. PMID- 8438196 TI - Long term results of surgical sphincterotomy in the treatment of choledocholithiasis. AB - The present article analyzes the indications for sphincterotomy in the Surgical Department of the University of Murcia, postoperative morbidity and mortality and the long term clinical situation of the patient after a follow-up period averaging 5.8 years. During a ten year period, a total of 2,610 patients underwent operation for biliary lithiasis, with exploratory choledochotomy indicated in 591 (22.6 percent). Surgical exploration of the bile duct finished with sphincterotomy in 135 (22.9 percent); 52 percent of these patients were less than 60 years old. The most frequent preoperative diagnosis was choledocholithiasis (33.3 percent) and cholelithiasis with crises of acute pancreatitis (30.3 percent). If we divide the ten years of the study into two five year periods, we noted a statistically significant decrease (p < 0.001) in the percentage of sphincterotomies compared with the number of choledochotomies performed during the second period. The rate of intra-abdominal complications was 5.1 percent; four intra-abdominal abscesses, one hemorrhaging at the level of the sphincterotomy and two instances of postoperative pancreatitis. Mortality in the series was 1.4 percent (two patients)--one with postoperative pancreatitis that developed torpidly and one with pulmonary embolism. Six years after the operation, 72.9 percent of the patients are still asymptomatic and the remaining patients have some type of symptoms--15.8 percent presented with dyspeptic syndrome; 2.0 percent had crises of colicky pain, and 5.9 percent required hospital admission for cholangitis. All of the patients with symptoms underwent endoscopy and ultrasonographic exploration of the bile duct. There were no pathologic findings in the biliary tree of patients who had dyspeptic syndrome or colicky pain, and all of the patients with cholangitis had a papillary stenosis and required endoscopic sphincterotomy or reoperation. PMID- 8438197 TI - Routine endometrial curettage is not indicated at the time of cervical cone biopsy. AB - Endometrial currettage is commonly performed after cervical cone biopsy to detect occult endometrial abnormalities. Recently, this practice has been questioned and specific criteria promulgated to reduce the number of concomitant endometrial curettages performed at the time of cone biopsy. To investigate the reliability of these criteria, we reviewed the records of 370 women who underwent cold-knife cervical cone biopsy, 323 (87.3 percent) of whom underwent concomitant endometrial curettage. Significant endometrial abnormalities were present in only 18 women, each of whom met at least one specific criterion for endometrial currettage. In contrast, 23 endometrial currettings either contained cervical tissue (five patients) or were insufficient for diagnosis (18 patients). The incidence of complications directly attributable to endometrial curettage was 1.6 percent. We conclude that limiting endometrial curettage at the time of cone biopsy to those women meeting specific criteria would significantly reduce the number of endometrial currettings performed, without hindering the ability to detect significant endometrial abnormalities. Such a reduction would minimize surgical morbidity and could save $13 million annually in the United States. PMID- 8438198 TI - A comparison of the gastric bypass and the gastric wrap for morbid obesity. AB - The standard for surgical treatment of morbid obesity is gastric reservoir reduction (GRR). The two popular techniques for GRR are the gastric bypass (GBP) and vertical banded gastroplasty. In 1981, a new approach to GRR, namely, the gastric wrap (GW) was introduced. The GW envelops the stomach in a customized Teflon (polytetrafluoroethylene) mesh. The current study compares, for the first time, the long term efficacy of GW and GBP. One hundred and five morbidly obese patients were studied. Fifty-two patients had GBP and 53 had GW. Preoperative and ideal weights averaged 301 and 129 pounds in the GW patients versus 278 and 123 pounds in the GBP patients. The two groups had similar age, height and co-morbid conditions. All patients survived the operation. After discharge, the patients had follow-up examinations at two weeks, two months, six months and then yearly. The GW was significantly more effective than the GBP in attaining and maintaining weight loss. The increased percent excess weight loss (percent EWL) was statistically significant at 12 months when the GW patients achieved 67 percent EWL compared with 57 percent EWL in the GBP patients. After the third year, the percent of EWL declined in the GBP patients, averaging 48 percent at four years and 47 percent at five years. In contrast, the GW patients maintained a 72 percent EWL at four years and a 66 percent EWL at five years. This weight loss was accomplished without nutritional embarrassment in both groups. The superiority of the GW in achieving and maintaining weight loss is reflected by the opinions of the patients regarding the attainment of preoperative objectives and their willingness to recommend GW to others. The downside of the GW is the higher incidence of reversal and the increased technical difficulties with reversal or revision compared with the GBP. PMID- 8438199 TI - Breast feeding after aesthetic mammary operations and cardiac operations through horizontal submammary skin incision. AB - In most aesthetic mammary operations, a certain amount of tissue remains connected with the areola complex. When performing horizontal submammary skin incision for median sternotomy, no mammary tissue is removed. Therefore, lactation should not be impaired after these operative procedures. We examined 107 patients after aesthetic mammary operation and 27 patients after horizontal submammary skin incision and asked for breast feeding attitudes. Only two of 22 patients with a delivery after operation could not breast feed their infants because of agalactia. In four patients, insufficient support might have been the main reason for primary ablactation. In 12 patients, we found reduced areola sensibility; however, asensibility was not observed. We did not find any correlation between areola sensibility and attitude of breast feeding. No patient reported severe complications because of breast feeding. From the current data, we can conclude that breast feeding is possible after aesthetic mammary operation or after a horizontal submammary skin incision for cardiac operation. Patients should be instructed before the mammary operation and encouraged during pregnancy to breast feed their infants. Scars in the region of the breast should not be a reason for primary ablactation. PMID- 8438200 TI - Economic impact of hospitalizations for lower abdominal adhesiolysis in the United States in 1988. AB - Much has been written about adhesion formation and prevention. Little is known about the number and cost of hospitalizations during which adhesiolysis is performed. This report describes the number of hospitalizations and days of care attributable to adhesiolysis in the United States and estimates the costs associated with these stays. The cost per hospital day and associated surgeons' fees are based on prevailing nationwide charges. During 1988, there were 281,982 hospitalizations during which adhesiolysis was performed, accounting for 948,727 days of inpatient care. These hospitalizations were responsible for an estimated $1,179.9 million in expenditures, of which $925.0 million was associated with hospital costs and $254.9 million with surgeons' fees. This estimate does not include outpatient costs and indirect costs. The results of this study demonstrate substantial costs associated with hospitalizations for adhesiolysis. Further understanding and prevention of adhesions may help to reduce unnecessary morbidity and mortality rates. PMID- 8438201 TI - The surgical treatment of Graves' disease. AB - A series of 215 patients treated surgically for Graves' disease between 1981 and 1988 were studied and compared with an earlier series of 105 patients operated upon in the same establishment between 1966 and 1980. More than 85 percent of the patients in the two series had long term follow-up evaluation. Surgical complications were rare in both series, with an overall morbidity rate of 2.7 percent, the rate of permanent recurrent laryngeal paralysis decreasing from 1 to zero percent and that of permanent hypoparathyroidism increasing from 1.0 to 1.9 percent. The incidence of residual or recurrent hyperthyroidism decreased markedly from 11.0 to 3.7 percent. This improvement can no doubt be attributed to bilateral subtotal lobectomy having been abandoned in favor of total lobectomy on one side and subtotal on the other. In contrast, this approach increases the incidence of hypothyroidism, with the rate rising from 13.0 to 48.7 percent. Long term monitoring is always necessary because results change during the course of time. PMID- 8438202 TI - A new and simple approach to open laparoscopy. AB - This new and simple approach to laparoscopy should be in the armamentarium of every laparoscopic surgeon. Similar to the dissection involved with an open peritoneal lavage, the peritoneal cavity is entered. After placement of a pursestring fascial suture, the introducer and laparoscope are inserted. The suture is used to provide an airtight seal and close the defect at the termination of the procedure. We believe that this is a safe, rapid, effective technique that is easy to learn. PMID- 8438203 TI - A simplified technique for ileal J-pouch construction. AB - A stapling technique for construction of an ileal J-pouch is presented. The technique is simple, minimizes the chances for pelvic contamination and avoids midpouch enterotomies. By postponing the performance of the apical enterotomy until after the pouch is in the definitive position, the apical enterotomy is placed exactly where needed to facilitate the subsequent ileoanal anastomosis. PMID- 8438204 TI - A simplified approach to superficial inguinal dissection with sparing of the saphenous vein in patients with carcinoma of the vulva. PMID- 8438205 TI - Piggyback orthotopic intestinal transplantation. PMID- 8438206 TI - Fetal wound healing. AB - Multiple distinctions concerning the adult and fetal wound healing processes exist. In the fetus, a minimal inflammatory response to wounding is seen with a marked deposition of glycosaminoglycans, particularly hyaluronic acid. Collagen seems to be present in small amounts and is rapidly and efficiently organized into structural nonscarred tissue components, a process that seems to be uniquely influenced by the ECM and its components. The exact mechanisms of control of growth, development and healing in the fetus are unclear, although a transition from fetal to adult processes takes place in utero. Furthermore, some processes may, in part, transiently reappear in healing wound found in adults. Clearly, there is a vast horizon for future investigation. The concept of fetal surgical treatment has become a reality. Many observations made in this field may well be applied in future attempts to prevent pathologic healing, and may even yield wounds far superior to the predicted "normal" results we see today. The future of wound manipulations may involve the crafting of complex matrices interwoven with a variety of cytokinetic agents, which could result in a healed wound or regenerated tissue that is mechanically and functionally equivalent to adjacent unwounded tissue. Furthermore, if the secrets of fetal healing can be revealed, areas of clinical intervention may be expanded to aid in controlling other abnormal patterns of tissue growth observed in clinical medicine as well. PMID- 8438207 TI - Mechanism of self-tolerance to endocrine tissue. PMID- 8438208 TI - Genetics of autoimmune endocrine diseases. PMID- 8438210 TI - Autoimmune Addison's disease. PMID- 8438211 TI - Immunity to the thyroid-stimulating hormone receptor. PMID- 8438212 TI - Variations in the incidence of sudden infant death syndrome (SIDS), United States, 1980-1988. AB - Sudden infant death syndrome (SIDS) continues to be the second leading cause of infant mortality in the United States. In 1989, 5,634 SIDS cases were recorded, resulting in a rate of 139.4 per 100,000 live births. While this 1989 rate was less than 1 percent below that in 1988, it was the second lowest of the decade. As with total infant mortality rates, SIDS rates have been slowly declining over the years but remain disproportionately higher among black infants than white. Unlike the total infant death rates, however, the gap between the races is narrowing--SIDS death rates among black infants decreased 19 percent between 1980 and 1988, in contrast to the 4 percent drop among white infants during the same period. The black-to-white ratio dropped from 2.18:1 in 1980 to 1.83:1 in 1988. Geographic differences in SIDS rates persist, with rates being the highest in the West and Midwest regions and lowest in the Northeast. While many SIDS risk factors have been and continue to be identified, the diagnosis remains one of exclusion. The etiology continues to elude definition, and increasingly more diagnoses are being made based on autopsy reports and death scene investigations. As these diagnostic practices become more standardized, SIDS prevalence is expected to change. Whether new insights will ultimately lead to eradication, remains unknown at this time. PMID- 8438209 TI - The immunologic insult in type 1 diabetes. PMID- 8438213 TI - Geographic profile of the aged. AB - The 1990 Census revealed that the number of persons aged 65 and over, especially those aged 85 and over, continue to grow rapidly. As a result, the nation's health, economic and social systems, already heavily impacted, will face escalating problems. However, there are extensive geographic variations in the sex differences and the number of elderly as well as in their rates of growth. For instance, while half of the nation's aged reside in just eight states, in some states they are a small fraction, and in others--such as Florida--they constitute a major portion. PMID- 8438214 TI - Tonsillectomy and adenoidectomy in-hospital charges, 1991. AB - Trends in tonsillectomy and adenoidectomy (T&A) procedure rates show a steady national decline since 1970. MetLife hospital T&A claims experience is analyzed for group policyholders and dependents during 1991. The total claims charges increased over the years while the number of in-hospital procedures decreased. The average cost to MetLife for a T&A in 1991 was $3,440, $2,910 in 1990 and $2,580 in 1989 among 625, 1,193 and 1,683 patients, respectively. The 1991 charges were the highest in the Pacific area and the lowest in the East North Central geographic area. Among states with ten or more T&As, Illinois led with charges 37 percent above the average. The lowest claims charges were reported in Maryland, 30 percent below the U.S. total. Average U.S. physician fees were $1,230 and comprised 36 percent of the total charges. This proportion varied from half of the total T&A charges in New York to one-quarter in South Carolina. Ancillary fees accounted for 77 percent of the hospital charges and ranged from just over half in California to 90 percent in South Carolina. Length of stay increased from 1.1 days in both 1989 and 1990 to 1.2 days in 1991. As increasing numbers of surgeons and patients are aware of and comfortable with the concept of outpatient surgeries and as more insurance plans include incentives for ambulatory surgeries, it seems clear that fewer uncomplicated T&As will be performed on an inpatient basis. PMID- 8438215 TI - Developments in medical care costs: an update. AB - The nation spent roughly $830 billion on all categories of medical care in 1992. Available data for personal health care expenditures and prices indicate that their increases slightly slowed last year, but the burden placed on the economy by the total health care sector continues to mount. Although the uncertainty of the Presidential election is over, the debate on health care reform will continue. PMID- 8438216 TI - Too much pretransfusion testing? PMID- 8438217 TI - Posttransfusion Serratia marcescens septicemia. PMID- 8438218 TI - The application of protein A immunoadsorption to remove platelet alloantibodies. PMID- 8438219 TI - Increased tumor necrosis factor alpha (TNF alpha), interleukin 1, and interleukin 6 (IL-6) levels in the plasma of stored platelet concentrates: relationship between TNF alpha and IL-6 levels and febrile transfusion reactions. AB - Increased interleukin 6 (IL-6) levels were found in 8 of 12 platelet concentrates (PCs) after 3 days of storage and in 10 of 12 PCs after 5 and 7 days of storage. Most of the PCs with an increased IL-6 level also showed increased tumor necrosis factor alpha (TNF alpha) and interleukin 1 beta (IL-1 beta) levels. Levels of IL 6 increased by 3 log10 over the base level during storage. Increased levels were found when the PC white cell count exceeded 3 x 10(9) per L. A linear correlation was found among the levels of TNF alpha, IL-1 beta, IL-1 alpha, and IL-6 in the PCs (r > 0.885). Comparison of the TNF alpha, IL-1 beta, and IL-6 levels in samples taken at various storage times indicates that the increased levels are the result of an active synthesis and release of interleukins during storage. In a second part of the study, 45 transfusions of white cell-reduced PCs were studied. Six transfusions were complicated by a febrile reaction. These reactions were related to high levels of IL-6 and TNF alpha in the PCs (p < 0.0001). These cytokines are known as endogenous pyrogens. These findings indicate that transfusion reactions might be due to the intravenous administration of plasma with high cytokine levels and might not always result from an antigen-antibody reaction. PMID- 8438220 TI - Transfusion-associated transmission of human T-lymphotropic virus types I and II: experience of a regional blood center. AB - During a 22-month period, 78,000 blood donors were screened for human T lymphotropic virus types I and II (HTLV-I/II) at Belle Bonfils Memorial Blood Center (Denver, Colorado). Positive donors and the living recipients of their previously donated blood components were evaluated for risk factors and symptoms related to HTLV-I infection, were screened by enzyme immunoassay, confirmed by Western blot for HTLV-I/II, and subsequently tested by polymerase chain reaction and peptide enzyme immunoassay to distinguish between HTLV-I and -II infection. Six seropositive blood donors (0.008%) were identified; four were typed as having HTLV-I infection and two as having HTLV-II. Of 18 living recipients of components from seropositive donors, none had risk factors for HTLV-I infection prior to transfusion and none had signs or symptoms of HTLV-I infection at follow-up. The mean time from transfusion to testing was 6.4 years. Seven recipients of HTLV-I infected components were HTLV seropositive; all were typed as having HTLV-I. A possible case of posttransfusion HTLV-I-associated myelopathy was identified in one patient who died before complete evaluation. One possible case of transfusion associated HTLV-II was identified. These data further support the continued screening of blood donors for HTLV-I/II. PMID- 8438221 TI - Absence of hepatitis B virus DNA detected by polymerase chain reaction in blood donors who are hepatitis B surface antigen negative and antibody to hepatitis B core antigen positive from a United States population with a low prevalence of hepatitis B serologic markers. AB - A recent study in hepatitis B surface antigen (HBsAg)-negative, antibody to hepatitis B core antigen (anti-HBc)-positive blood donors from a population with a high prevalence of hepatitis B serologic markers showed the presence of hepatitis B virus DNA (HBV DNA) as detected by polymerase chain reaction (PCR) in 4 percent of these donors. A sensitive, nested PCR assay was used to assess the prevalence of HBV DNA in a population of HBsAg-negative, anti-HBc-positive blood donors from a United States population with a low prevalence of hepatitis B serologic markers. The lower limit for detection by the PCR assay was 10(-5) pg per mL of HBV DNA. There was a review of 26,492 consecutive blood donations in a 12-month period. During this time, only 1 unit (0.004%) was HBsAg positive. An additional 158 units (0.6%) were repeatably reactive for anti-HBc. These 158 HBsAg-negative, anti-HBc-positive units were given by 119 donors of blood for allogeneic and autologous use. HBV DNA was not detected by PCR in blood from 83 allogeneic blood donors (93 samples) or 36 autologous blood donors (65 samples). Anti-HBc testing is an inefficient means of screening for potential hepatitis B infectivity and is associated with low test specificity in populations with a low prevalence of hepatitis B serologic markers. PMID- 8438222 TI - A retrospective study to determine the risk of red cell alloimmunization and transfusion during pregnancy. AB - A retrospective review of post-delivery antibody records was performed at a teaching hospital and a community hospital to determine the frequency of new red cell alloantibody production and transfusion during pregnancy. If alloantibody was undetected at delivery, it was assumed that alloimmunization had not occurred. When antibody was detected, a chart review was performed to determine if the antibody was present at the beginning of the pregnancy or was newly produced during the pregnancy. A total of 17,568 pregnancies were reviewed. Antibody was detected at delivery in 948 (5.4%) cases, of which 89.5 percent (848/948) involved passive anti-D or clinically insignificant antibodies. The remaining 100 pregnancies involved clinically significant IgG antibodies. In 58 pregnancies, the antibody was detected in the first trimester, and in 42, new antibody production occurred during the pregnancy. Thus, the prevalence of new antibody production during pregnancy was 0.24 percent (95% confidence interval [CI], 0.17-0.32). Transfusion records indicated that the prevalence of transfusions during pregnancy was 0.09 percent (95% CI, 0.04-0.14). None of the women with new alloantibody formation during their pregnancies required transfusion; hence, new alloantibody production and the need for transfusion appear to be independent events. The probability of these events occurring together was 2.1 x 10(-6), or 1 in 500,000 deliveries. PMID- 8438223 TI - Nosocomial epidemic of Serratia marcescens septicemia ascribed to contaminated blood transfusion bags. AB - Two cases of transfusion-related Serratia marcescens bacteremia prompted extensive epidemiologic investigations in three independent hospitals. Test tubes and plasma from donors whose blood was drawn into bags from a single production batch were cultured. Analysis of the ribotype of S. marcescens isolates was performed. For comparison, a strain from the production plant and eight other, unrelated bacteremia isolates were examined. In addition, a retrospective national survey was carried out. S. marcescens was cultured from 11 (0.73%) of 1515 blood units, and an additional (third) bacteremic patient was identified. The clinical isolates from three patients, the three units of blood transfused, and the plant-derived strain shared a unique ribotype. The incident is interpreted as a sporadic, bacterial contamination of blood bags with the S. marcescens epidemic strain, occurring during the manufacturing or packaging. A similar incident has not previously been reported. Attention is drawn to the possibility of significant contamination during the complex production of multiple-bag blood collection systems. Guidelines for improved registration and handling of transfusion complications in wards are suggested. Manufacturers should be encouraged to provide blood packs with sterile exteriors, in appropriate, single, outer packages. PMID- 8438224 TI - Strategies for the avoidance of bacterial contamination of blood components. AB - Gram staining and bacterial culturing methods were used to determine the incidence of bacterial contamination of cellular blood components at the time of transfusion reactions. Over a 5-year period, 2208 (4.3%) of 51,278 transfusions were complicated by reactions. Overall bacterial contamination occurred in 5 (0.03%) of 17,928 transfusions of single-donor apheresis platelets, 1 (0.14%) of 712 transfusions of pooled random-donor platelet concentrates, 1 (0.003%) of 31,385 transfusions of red cells, and 0 of 1253 transfusions of fresh-frozen plasma. Gram staining done at the time of positive cultures was positive in three of six cases. Although six of seven recipients of contaminated components suffered no clinical sequelae, contaminated transfusions may have been a contributing cause of death in one case. Attempts were made to avoid the transfusion of contaminated cellular blood components by performing routine bacterial cultures: 0 of 341 quality control cultures were positive. To avoid the transfusion of contaminated platelets by identifying bacteria, Gram staining was performed in all single-donor apheresis platelet units collected on open systems and daily in platelets stored > 48 hours: 8 (0.15%) of 5334 smears done on 3829 platelet units were interpreted as positive, and those units were not transfused, but only two of eight units were culture positive. These studies suggest that bacterial contamination can result in adverse clinical sequelae in transfusion recipients and that both culturing and Gram staining are poor methods of screening for contaminated units. More sensitive and specific methods of generalized screening for bacterial contamination are needed. PMID- 8438225 TI - Treatment of refractoriness to platelet transfusion by protein A column therapy. AB - Ten thrombocytopenic patients (platelets < 10-24 x 10(9)/L) who were refractory to platelet transfusion were investigated for their responsiveness to staphylococcal protein A column therapy. Nine patients had previously been treated with steroids, intravenous immune globulin, and/or other forms of immunosuppressive therapy without improvement in their transfusion response. All patients were receiving multiple platelet transfusions without achieving 1-hour corrected count increments (CCIs) > or = 7500. Eight patients had antibodies that reacted with platelets and were directed against HLA class I antigens, ABO antigens, and/or platelet-specific alloantigens. Plasma (500-2000 mL) from each patient was passed over a protein A silica gel column and then returned to the patient. Patients received from 1 to 14 treatments. A positive response to protein A therapy was defined as at least a doubling of the pretreatment platelet count and/or two successive 10- to 120-minute posttransfusion CCIs > or = 7500. Following plasma treatments, 6 of 10 patients responded with daily platelet counts that averaged 48 +/- 11 x 10(9) per L as compared with counts of 16 +/- 7 x 10(9) per L (p < 0.0005) before treatment. Posttransfusion CCI values determined in four of these patients averaged 2480 +/- 810 and 10,010 +/- 3540 (p < 0.005) before and after treatment, respectively. In contrast, among the four unresponsive patients, platelet counts averaged 10 +/- 9 and 13 +/- 10 x 10(9) per L (p = NS), respectively, while posttransfusion CCIs were 700 +/- 1410 and 1520 +/- 2460 (p = NS), respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8438226 TI - Plasma exchange does not improve survival in a canine model of human septic shock. AB - Whether plasma exchange would improve survival in antibiotic-treated canines with septic shock was investigated. Escherichia coli O86H8 (1.4 X 10(10)) was surgically implanted as an intraperitoneal clot in 18 two-year-old (10-12 kg) purpose-bred beagles. Beginning 4 hours after surgery, all animals received cefoxitin and gentamicin for 5 days. Three treatment groups were defined: 1) a no apheresis, or control group, (n = 6); 2) a sham apheresis group, whose whole blood plasma was removed, separated, and then transfused (n = 6); and 3) a plasma exchange group from whom blood and plasma were removed and separated, to whom the blood was returned, and in whom infected plasma was replaced with compatible fresh-frozen canine plasma (n = 6). For the sham apheresis and plasma exchange groups, a commercial blood cell processor was used to separate 1.5 blood volumes of plasma at 5 and 24 hours after surgery. Serial radionuclide left ventricular ejection fractions and femoral and pulmonary arterial catheter hemodynamics were measured simultaneously in awake animals. All six animals in the plasma exchange group died. In both the sham and control groups, only one of six animals survived. Survival times were ordered (median in hours) (control [372 h] > sham apheresis [48 h] > plasma exchange [24 h] [p < 0.038]). Decreases in mean cardiac index and mean arterial pressure (from before apheresis to after) at 5 to 7 hours after surgery were ordered (plasma exchange > sham apheresis > control; p < 0.03). Thus, plasma exchange in this controlled trial of septic shock was associated with decreased survival and worsened hemodynamics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8438227 TI - A flow cytometric method for counting very low levels of white cells in blood and blood components. AB - Reduction of white cells (WBCs) in blood components may reduce the risk of virus transmission and HLA alloimmunization. Filtration provides a means by which to achieve high-efficiency WBC reduction. A method has been developed using flow cytometry to quantitate the number of WBCs in WBC-reduced packed red cells or platelet concentrates. This method uses a detergent and propidium iodide (PI) solution to label the WBC nuclei and incorporates a known amount of fluorescein isothiocyanate (FITC)-labeled chicken red cells (cRBCs) into the mixture as an indicator of the volume examined. The number of observed WBCs per mL is calculated as follows: Number of PI WBC nuclei events/Number of FITC cRBC events x Number of FITC cRBCs added to mixture/Volume of blood in mixture. The method may allow the detection of WBCs at a concentration as low as 0.01 per microliters (10/mL) in a blood sample. It is an efficient method of collecting data, as it requires less than 10 minutes per sample. This flow cytometric technique is suitable for research purposes and for quality control of WBC-reduced blood components, because it is precise and can be used to quantitate WBCs in large or small numbers in a sample. PMID- 8438228 TI - ABO errors. PMID- 8438229 TI - Method for counting white cells (WBCs) in WBC-reduced red cell concentrates. PMID- 8438230 TI - Untangling the energetics of protein folding. PMID- 8438231 TI - A major superfamily of transmembrane facilitators that catalyse uniport, symport and antiport. AB - Many transport proteins of bacteria and eukaryotes are thought to possess a common structural motif of 12 transmembrane-spanning alpha-helical segments. In this report we use statistical methods to establish that five families or clusters of these facilitators comprise a single superfamily. The five clusters include: (1) drug-resistance proteins, (2) sugar facilitators, (3) facilitators for Krebs cycle intermediates, (4) phosphate ester-phosphate antiporters and (5) a distinct group of oligosaccharide-H+ symporters. Over 50 transporters of bacteria, lower eukaryotes, plants and animals, and one putative bacterial transcriptional regulatory protein are members of this superfamily, which we term the 'major facilitator superfamily' (MFS). PMID- 8438232 TI - News from the interface: the molecular structures of triacylglyceride lipases. AB - Neutral lipases constitute one of the most ubiquitous and diverse families of enzymes. The recently solved crystal structures of three lipases show that enzymatic hydrolysis occurs with the assistance of a catalytic triad, which is structurally reminiscent of serine proteinases. However, these lipases only become active at the oil-water interface through a conformational change that exposes the active centre of the enzyme. PMID- 8438233 TI - Experimental application of top-down control analysis to metabolic systems. AB - Metabolic control analysis (MCA) has provided the language and framework for quantitative study of control over flux, or over metabolites, by individual enzymes of a pathway. By contrast, top-down control analysis (TDCA) yields an immediate overview of the control structure of the whole system of interest, giving information about the control exercised by large sections of complex pathways. Unlike MCA, TDCA does not rely on the use of specific inhibitors or genetic manipulation to determine control coefficients. The method and an application of TDCA to ketogenesis are described. PMID- 8438234 TI - Hot line to the secretory pathway. PMID- 8438235 TI - Pre-tRNA splicing: variation on a theme or exception to the rule? AB - There has been a growing recognition that there are many conserved features among apparently diverse RNA splicing systems, suggesting that they may have a common origin. However, pre-tRNA splicing is an apparent exception in nearly all respects. Features of this unique class should be considered in any comprehensive discussion of the origin(s) of splicing and its implications for the evolution of gene structure. PMID- 8438236 TI - The yeast open reading frame encoding a dual specificity phosphatase. PMID- 8438237 TI - Membrane traffic wardens and protein secretion in gram-negative bacteria. AB - Recent progress in the genetic analysis of protein secretion in diverse Gram negative bacteria has revealed three major, highly conserved but functionally independent pathways that involve accessory apparatus proteins. Protein secretion via the Type I pathway is signal sequence-independent with no free periplasmic intermediate. Secretion by the Type II pathway is signal sequence-dependent and via the periplasm. Recent results also suggest that a third (Type III) secretory pathway exists in which protein secretion is signal sequence-independent. PMID- 8438238 TI - Convocation. PMID- 8438239 TI - Lysis of endothelial cells by graft-infiltrating lymphocytes after clinical heart transplantation. PMID- 8438240 TI - CD4+ T-cell-dependent destruction of MHC class I disparate cardiac allografts. PMID- 8438241 TI - Cytokines and transplantation. PMID- 8438242 TI - Interleukin-2 receptor signal transduction: translocation of active serine threonine kinase Raf-1 from IL-2 receptor into cytosol depends on IL-2-induced tyrosine kinase activation. PMID- 8438243 TI - Cells infiltrating rejected human kidney allografts secrete IFN-gamma, IL-6, and IL-10, and are modulated by IL-2 and IL-4. PMID- 8438244 TI - Cytokine mRNA expression during development of acute rejection in murine cardiac allografts. PMID- 8438245 TI - Mixed lymphocyte kidney and islet cell cocultures: the effect of IFN-gamma and anti-IFN-gamma. PMID- 8438246 TI - Treatment with rapamycin blocks arterial intimal thickening following mechanical and alloimmune injury. PMID- 8438247 TI - Activation of lymphokine mRNA and protein synthesis in vivo in a murine graft-vs host reaction. PMID- 8438248 TI - Interleukin-2 antisense oligonucleotides inhibit T-cell function. PMID- 8438249 TI - Intragraft eosinophilia and interleukin-5 mRNA accompany liver allograft rejection. PMID- 8438250 TI - Monoclonal anti-tumor necrosis factor-alpha antibody suppresses rejection, but enhances infectious complications in rat liver allograft recipients. PMID- 8438251 TI - Long-term storage of liver grafts is associated with a postoperative elevation of tumor necrosis factor: a possible role in the pathogenesis of primary nonfunction of the graft and pulmonary complications. PMID- 8438252 TI - Role of HLA-DP antigen in xenogeneic iso-skin grafts using transgenic mice. PMID- 8438253 TI - Antifection: a new method for targeted gene transfection. PMID- 8438254 TI - Renal tubular cell expression of MHC class II (I-Eb) is insufficient to initiate immune injury in a transgenic kidney transplant model. PMID- 8438255 TI - Loss of heparan sulfate proteoglycan as a manifestation of cellular immunity in vivo and in vitro. PMID- 8438256 TI - Lymphocyte adhesion to allogeneic endothelium involves at least four different pathways. PMID- 8438257 TI - Medawar Prize Lecture. Liver allo- and xenotransplantation. PMID- 8438258 TI - Influence of oncogenes and cell metabolism on immunogenicity and tolerogenicity of a model macrophage cell line. PMID- 8438259 TI - Modulation of ongoing antibody synthesis by antibody-coated platelets in the rat: opposite effects of antibody classes. PMID- 8438260 TI - HLA, anthropology, and transplantation. PMID- 8438261 TI - Diversity in mRNA encoding soluble form MHC class I-like molecules in human renal tissues. PMID- 8438262 TI - HLA 1992: typing strategies and perspectives in bone marrow transplantation. PMID- 8438263 TI - Revisiting HLA matching for kidney transplantation. PMID- 8438264 TI - Workshop report: clinical relevance of new crossmatching techniques. PMID- 8438265 TI - Sequence-specific interactions of the nuclear proteins with polymorphic upstream regulatory regions of HLA-DRB genes. PMID- 8438266 TI - Rejection of skin allografts by indirect allorecognition of donor class I major histocompatibility complex peptides. PMID- 8438267 TI - Molecular characterization of endothelial cell antigens involved in renal allograft rejection. PMID- 8438268 TI - T-cell recognition of donor class I major histocompatibility complex peptides during allograft rejection. PMID- 8438269 TI - A simple and practical test of HLA-DRB and -DQB matching in transplantation. PMID- 8438270 TI - Polymerase chain reaction-single-strand conformation polymorphism analysis of HLA DP genes and its application in transplantation. PMID- 8438271 TI - Efficacy of sequence-specific oligotyping in determining HLA-DR compatibility in cadaver kidney transplantation. The North Italy Transplant Program Working Group on Improvement of Kidney Transplantation. PMID- 8438272 TI - The transplantation society meeting in Paris. PMID- 8438273 TI - HLA-DR matching is effective in reducing posttransplant costs in renal allograft recipients on triple therapy. PMID- 8438274 TI - Does previous breast feeding affect maternal donor renal allograft outcome? A single-institution experience. PMID- 8438275 TI - Effect of reexposure to mismatched major histocompatibility complex antigens on renal retransplant allograft survival. PMID- 8438276 TI - Reduction of the center effect by HLA matching. PMID- 8438277 TI - Role of HLA matching in cadaveric renal transplantation--influence of improved serologic HLA-DR typing. PMID- 8438278 TI - Significance of HLA-DR matching at the DNA level in clinical renal transplantation. PMID- 8438279 TI - HLA-B mismatch: an equally strong prognostic factor for kidney transplantation when compared with HLA-DR mismatch. PMID- 8438280 TI - Role of donor-recipient HLA disparity in the development of humoral immune reactions in corneal transplantation. PMID- 8438281 TI - Living-related kidney transplant or simultaneous pancreas-kidney for diabetic renal failure? PMID- 8438282 TI - Degree of HLA mismatch as a predictor of death from allograft arteriopathy after heart transplant. PMID- 8438283 TI - Effects of DR mismatch on long-term graft survival in simultaneous kidney pancreas transplantation. PMID- 8438284 TI - HLA-A2-specific antibody production in severe combined immunodeficient mice reconstituted with human peripheral blood leukocytes from HLA-presensitized donors. PMID- 8438285 TI - Delayed elimination of donor red blood cells is associated with host major histocompatibility complex and donor-specific blood transfusion enhancement of rat renal allograft survival. PMID- 8438286 TI - Anti-HLA antibodies: detection and effect on renal transplant function. PMID- 8438287 TI - Flow cytometry crossmatching for kidney transplantation. PMID- 8438288 TI - Clinical relevance of a positive B-cell crossmatch on renal transplantation: a multi-transplant center evaluation. PMID- 8438289 TI - Xenotransplantation: a view to the future. PMID- 8438290 TI - Computer algorithm that predicts both acceptable and unacceptable private and public HLA class I antigens in highly sensitized patients. PMID- 8438292 TI - Strategy for improving retransplantation in the CyA era. PMID- 8438291 TI - Preformed antibodies in sensitized recipients: effect of immunoglobulin titer, class, and specificity on liver and heart allografts. PMID- 8438293 TI - Value of flow cytometric monitoring of posttransplant antibody status in renal transplantation. PMID- 8438294 TI - Effect of anti-HLA antibodies on the long-term survival of heart and kidney allografts. AB - Study of anti-HLA antibodies in a population of 238 primary renal and 199 primary heart allograft recipients showed significant association between development of anti-HLA antibodies and that of chronic allograft rejection. The 5-year renal allograft survival was 70% in recipients without antibodies and 53% in recipients who developed anti-HLA alloantibodies during the first year following transplantation. Heart allograft survival at 5 years was 91% in patients without and 78% in patients with antibodies during the first 12 months posttransplantation. Development of antibodies is associated with acute rejection episodes and probably with the release of soluble HLA antigens. PMID- 8438295 TI - Importance of HLA matching in highly sensitised renal transplant recipients with high transplant survival rates. The Manchester Kidney Transplant Team. PMID- 8438296 TI - Crossing the ABO blood barrier in renal transplantation. PMID- 8438297 TI - ABO-incompatible kidney transplantation in a single-center trial. PMID- 8438298 TI - Local immune states in ABO-incompatible renal allografts. PMID- 8438299 TI - Induction of tolerance in immature and mature T cells. PMID- 8438300 TI - Anergy in allogeneic transplantation. PMID- 8438301 TI - Intrathymic islet allografts prevent hyperglycemia and autoimmune beta-cell destruction in BB rats following transplantation in the prediabetic period. PMID- 8438302 TI - Reduction in donor-specific cytotoxic T lymphocytes and prolonged cardiac allograft survival following intrathymic donor splenocyte injection. PMID- 8438303 TI - Medullary thymic epithelium induces tolerance to allogeneic major histocompatibility complex class I antigens. PMID- 8438304 TI - Prolongation of islet allografts by pretreatment with intrathymic UV-B donor spleen cells. PMID- 8438305 TI - Donor-specific tolerance to cardiac, but not renal, allografts is induced by intrathymic transfer of donor splenocytes. PMID- 8438306 TI - Prolonged survival of rat cardiac allografts after intrathymic inoculation of donor thymocytes. PMID- 8438307 TI - Tolerance induction to skin allografts following intrathymic injection with donor specific splenocytes in major histocompatibility complex class I, class I+MLS, and class I+II disparities. PMID- 8438308 TI - Induction of specific unresponsiveness to rat cardiac allografts by pretreatment with intrathymic donor major histocompatibility complex class I antigens. PMID- 8438309 TI - Knock-out mice: a new tool for transplantation immunologists. PMID- 8438310 TI - Intrathymic inoculation of islets at birth prevents autoimmune diabetes and pancreatic insulitis in the BB rat. PMID- 8438311 TI - Intrathymic injection of donor antigen-presenting cells prolongs heart graft survival. PMID- 8438312 TI - Donor antigen-specific T-lymphocyte deletion after intrathymic inoculation. PMID- 8438313 TI - Induction of immune unresponsiveness by intrathymic injection of allogeneic cells in a murine model. PMID- 8438314 TI - Neonatal induction of transplantation tolerance in mice is associated with in vivo expression of IL-4 and -10 mRNAs. PMID- 8438315 TI - Decreased IFN-gamma and IL-2 mRNA expression in peripheral tolerance to heart allografts with conserved granzyme A, perforin, and MHC antigens mRNA expression. PMID- 8438316 TI - Role of interferon-gamma in the induction of clonal deletion after injection of staphylococcal enterotoxin B. PMID- 8438317 TI - Tolerance induction in human kidney retransplantation: impact of repeated HLA mismatches in 156 second renal grafts. PMID- 8438318 TI - Interleukin-2 reverses the ability of cyclosporine to induce tolerance to class I disparate kidney allografts in miniature swine. PMID- 8438319 TI - Th2-like effectors may function as antigen-specific suppressor cells in states of transplantation tolerance. PMID- 8438320 TI - Peripheral tolerance specific for host minor histocompatibility antigens in acute GVHR-protected mice is associated with functional deletion of CD4+ but not CD8+ T cells and an active suppressive mechanism. PMID- 8438321 TI - Mechanism of allograft tolerance in nonhuman primates: purification of a specific isotype of IgG with suppressor activity. PMID- 8438322 TI - Body parts: the modern dilemma. PMID- 8438323 TI - Thy 1+ donor cells function as veto cells in the maintenance of tolerance across a major histocompatibility complex disparity in mixed-lymphoid radiation chimeras. PMID- 8438324 TI - Persistence of donor-reactive T cells after liver transplantation-induced tolerance in mice. PMID- 8438325 TI - Xenotransplantation from pig to cynomolgus monkey: approach toward tolerance induction. PMID- 8438326 TI - Donor bone marrow infusion suppresses alloantibody response in RATG-treated recipients: a correlate of long survival. PMID- 8438327 TI - Effect of depleting CD3+ cells from DR- donor bone marrow to facilitate kidney graft tolerance in recipients given total lymphoid irradiation. PMID- 8438328 TI - Impact of perioperative portal venous administration of donor lymphocytes on survival of rat cardiac allografts and renal grafts of the mongrel dog. PMID- 8438329 TI - Tolerance induction using autologous bone marrow modified with an allogeneic class I MHC gene. PMID- 8438330 TI - In vitro and in vivo activities of long-term cultured veto suppressor clones. PMID- 8438331 TI - Prolonged survival of hepatic and cardiac allografts by i.v. injection of donor spleen cells following splenectomy in rats: possible mechanisms involved in tolerance induced by intraportal injection of donor antigens. PMID- 8438332 TI - Ontogeny of tolerogen-responsive lymphocytes following neonatal inoculation of class II disparate semiallogeneic cells. PMID- 8438333 TI - Induction of immunity and oral tolerance to alloantigen by polymorphic class II major histocompatibility complex allopeptides in the rat. PMID- 8438334 TI - Induction of specific unresponsiveness using transfected cells expressing donor major histocompatibility complex molecules: evidence for indirect presentation of allopeptides in vivo. PMID- 8438335 TI - Anti-V beta TcR monoclonal antibodies identify and can activate anergic T cells from mice rendered neonatally tolerant of class II alloantigens. PMID- 8438336 TI - Liver graft induced donor specific unresponsiveness without class I and/or class II antigen differences. PMID- 8438337 TI - Effect of tolerance to allogeneic major histocompatibility complex antigens on rejection across minor antigen differences. PMID- 8438338 TI - Insights into the mechanism of allograft acceptance in T-cell receptor (beta chain) transgenic mice. PMID- 8438339 TI - Alterations in peripheral V beta 11+ T-cell populations are not predictive of allograft rejection in I-E- mice resistant to neonatal tolerance induction. PMID- 8438340 TI - Continued presence of donor leukocytes in recipients of liver grafts. PMID- 8438341 TI - Donor-specific tolerance induced by non-major histocompatibility complex disparate kidney grafts for subsequent pancreas transplants. PMID- 8438342 TI - Specific intravenous carbohydrate therapy: a new approach to the inhibition of antibody-mediated rejection following ABO-incompatible allografting and discordant xenografting. PMID- 8438343 TI - Study of the target antigens of hyperacute xenogeneic rejection in discordant combinations. PMID- 8438344 TI - Administration of nonanticoagulant heparin inhibits the loss of glycosaminoglycans from xenogeneic cardiac grafts and prolongs graft survival. PMID- 8438345 TI - Long-term survival of xenogeneic skin grafts in widely disparate combinations. PMID- 8438346 TI - Depletion of preformed antibody in primates for discordant xenotransplantation by continuous donor organ plasma perfusion. PMID- 8438347 TI - Prolongation of cardiac xenograft survival by pre- and posttransplant splenectomy is associated with a decrease in anti-donor antibody titers. PMID- 8438348 TI - Relationship between human natural anti-A, anti-B alloantibodies and anti-pig xenoantibodies. PMID- 8438349 TI - Consent for organ donation: what are the ethical principles? PMID- 8438350 TI - Characterization of human antibodies that are cytotoxic to pig aortic endothelial cells. PMID- 8438351 TI - CD46 (MCP) confers protection from lysis by xenogeneic antibodies. PMID- 8438352 TI - Complement depletion prolongs discordant cardiac xenograft survival in rodents and non-human primates. PMID- 8438353 TI - Dedication of the XIVth International Congress of the Transplantation Society- the Jean Hamburger Memorial Congress--and citations. PMID- 8438354 TI - Inhibitory effect of the complement receptor-specific monoclonal antibody on the induced antibody response and the role of CD4+ and CD8+ T-cells in the rat to mouse xenotransplantation. PMID- 8438355 TI - Effectiveness of combination therapy using cobra venom factor, splenectomy, and deoxyspergualin in guinea pig to rat cardiac xenografts. PMID- 8438356 TI - Prolonged survival of guinea pig-to-rat heart xenografts using repeated low doses of cobra venom factor. PMID- 8438357 TI - Effect of repetitive doses of soluble human complement receptor type 1 on survival of discordant cardiac xenografts. PMID- 8438358 TI - Deoxyspergualin and rabbit antithymocyte globulin markedly prolong discordant pig pancreatic islet xenografts. PMID- 8438359 TI - Long-term suppression of natural and graft-induced xenophile antibodies by short term antigen-cyclophosphamide treatment. PMID- 8438361 TI - Alternative sources of clinically transplantable vital organs. PMID- 8438360 TI - Splenectomy is a potent immunosuppressive modality for cardiac xenografting. PMID- 8438362 TI - Consistent prolonged "concordant" survival of hamster-to-rat cardiac xenografts by inhibition of anti-species antibodies with methotrexate. PMID- 8438363 TI - Effects of cholera toxin in xenograft survival. PMID- 8438364 TI - Anti-CD4 monoclonal antibody treatment in hamster-to-rat cardiac transplantation: cytotoxic antidonor antibodies detected by a new flow cytometric complement dependent cytotoxicity assay. PMID- 8438365 TI - Continuous administration of methyldeoxyspergualin prolongs xenograft survival in hamster-to-rat cardiac transplantation. PMID- 8438366 TI - Modulation of acute and hyperacute rejection of xenografts in concordant hamster to-rat combination. PMID- 8438367 TI - Effect of bursectomy on deposition of natural xenoreactive antibodies and complement within rat cardiac xenografts in the chicken. PMID- 8438369 TI - Xenoreactive T-cell lines initiate pancreatic islet graft destruction in vivo. PMID- 8438368 TI - Long-term functional xenograft tolerance after intrathymic islet transplantation (Lewis rat-->B6 mouse). PMID- 8438370 TI - Human antiporcine mixed lymphocyte reaction. PMID- 8438371 TI - Cytokine messenger RNA profiles in hamster-to-rat liver xenografts. PMID- 8438372 TI - Allogeneic and xenogeneic cross-reactions in hyperimmune recipients. PMID- 8438373 TI - Role of activated natural killer and CD4+, CD8+ cells in the cellular rejection of a discordant xenograft. PMID- 8438374 TI - Human humoral immune reactions against pig antigens: a method to clear preexisting preformed natural antibodies. PMID- 8438375 TI - Long-term chimera produced by transplantation of human fetal liver cells into severe combined immunodeficiency mice. PMID- 8438376 TI - Effect of primary xenograft or allograft on the rejection of a subsequent allograft. PMID- 8438377 TI - Xenoreactivity in mouse + rat-->mouse chimeras. PMID- 8438378 TI - Xenogeneic orthotopic liver transplantation in nonhuman primates. PMID- 8438379 TI - Humoral reaction to microencapsulated rat, canine, and porcine islet xenografts in spontaneously diabetic NOD mice. PMID- 8438380 TI - Comparative immunopathologic study of hyperacute rejection in naive and sensitized rodent cardiac xenograft models. PMID- 8438381 TI - Drug development and testing in relation to cell migration and chimerism. PMID- 8438382 TI - Is there a need for pancreas transplantation? Pro. PMID- 8438383 TI - Therapeutic monoclonal antibodies in transplantation. PMID- 8438384 TI - Prevention of graft-versus-host disease after bone marrow and small bowel transplantation by ultraviolet B modulation of bone marrow cells. PMID- 8438385 TI - Peptides corresponding to T-cell receptor-HLA contact regions inhibit class I restricted immune responses. PMID- 8438386 TI - Specificity of donor bone marrow cells that abrogate second-set allograft rejection. PMID- 8438387 TI - Peptide from one of the alpha helical regions of H-2Kb can manipulate responses to the H-2Kb alloantigen in vitro and in vivo. PMID- 8438389 TI - Single pretransplant donor-specific transfusion in cadaver and living related donor renal transplantation. PMID- 8438388 TI - Peptides corresponding to the CD8 binding region of HLA class I block the differentiation of cytotoxic T lymphocyte precursors. PMID- 8438390 TI - Intrathymic inoculation of donor cells promotes survival of rat orthotopic liver allografts. PMID- 8438391 TI - Pretreatment with irradiation and donor-specific transfusion prolongs survival in small intestinal transplantation. PMID- 8438392 TI - Selective changes in human T-cell receptor repertoire after blood transfusion. PMID- 8438393 TI - Ex vivo perfusion of the cluster graft with anti-class II antibody can significantly prevent acute rejection in swine abdominal organ cluster transplantation. PMID- 8438394 TI - Serum suppressive factor appears to potentiate cardiac allograft survival after portal vein injection of ultraviolet B-irradiated donor spleen cells. PMID- 8438395 TI - Ten years' experience with cyclosporine monotherapy after renal transplantation. PMID- 8438396 TI - Is cyclosporine-associated glomerulopathy a new glomerular lesion in renal allografts using CyA? PMID- 8438397 TI - Cyclosporine and rapamycin block protein kinase C-mediated induction of the activation signal, activator of DNA replication, in cell-free assay. PMID- 8438398 TI - Is there a need for pancreas transplantation? Con. PMID- 8438399 TI - Cyclosporine preferentially inhibits clonal deletion of CD8-positive T cells with an MHC class II restricted autoreactive T-cell receptor. PMID- 8438400 TI - Nuclear membrane-associated cyclophilins of potential importance in cyclosporine immunosuppression. PMID- 8438401 TI - European multicentre trial of cyclosporine in renal transplantation: 10-year follow-up. PMID- 8438402 TI - Effect of cyclosporine on chronic vascular rejection in an inbred rat cardiac model. PMID- 8438403 TI - Temporary immunosuppression for peripheral nerve allografts. PMID- 8438404 TI - Studies on morphological outcome of cyclosporine-associated arteriolopathy after discontinuation of cyclosporine in patients with renal allografts. PMID- 8438405 TI - TCR alpha/beta targeted therapy in the rat: pretreatment with R73 monoclonal antibody induces profound immunological anergy and long-term allograft survival. PMID- 8438406 TI - Comparison of T10Bg.1A-31 and OKT3 in treating acute renal allograft rejection. PMID- 8438407 TI - Immunosuppressive effects of anti-CD3 MAb and soluble co-stimulatory molecules. PMID- 8438408 TI - Do prophylactic antilymphocyte globulins (ALG and OKT3) improve renal transplant survival in recipient and donor high-risk groups? PMID- 8438409 TI - Regulated commercialism of vital organ donation: a necessity? Con. PMID- 8438410 TI - Results of a prospective, randomized double-blind study comparing standard vs low dose OKT3 induction therapy. PMID- 8438411 TI - Low-dose OKT3 induction therapy following renal transplantation leads to improved graft function and decreased adverse effects. PMID- 8438412 TI - OKT3 prophylaxis in liver transplant patients: a European and Australian multicenter, prospective controlled trial. PMID- 8438413 TI - OKT3 antibody response study (OARS): a multicenter comparative study. PMID- 8438414 TI - Suppression of OKT3-induced tumor necrosis factor alpha formation by pentoxifylline in renal transplant recipients. PMID- 8438415 TI - Cytokine-related encephalopathy induced by OKT3: incidence and predisposing factors. PMID- 8438416 TI - Activation of coagulation and fibrinolysis during treatment with OKT3. PMID- 8438417 TI - In vivo induction of IL-10 by anti-CD3 monoclonal antibody in mice. PMID- 8438418 TI - Prophylactic OKT3 monoclonal antibody versus antilymphocyte globulins: a prospective, randomized study in 148 first cadaver kidney grafts. PMID- 8438419 TI - Morbidity of intraoperative OKT3 administration in primary cadaveric renal transplant recipients. PMID- 8438421 TI - Association of sensitization to horse antilymphocyte/thymocyte globulin with recipient age and decreased renal allograft survival rates. PMID- 8438420 TI - Is the routine use of induction immunosuppression with ALG or OKT3 justified in cadaveric renal transplantation? PMID- 8438422 TI - Regulated commercialism in transplantation: the factitious focus. PMID- 8438423 TI - Initiation of ALG pretransplant reduces the incidence of delayed renal allograft function. PMID- 8438424 TI - Optimal combination of immunosuppressive agents for renal transplantation: first report of a multicentre, randomised trial comparing cyclosporine+prednisolone with cyclosporine+azathioprine and with triple therapy in cadaver renal transplantation. The Australian Collaborative Trials Committee. PMID- 8438426 TI - Quadruple induction immunosuppression after liver transplantation with IL-2 receptor antibody (BT 563) is equally effective and better tolerated than ATG induction therapy. PMID- 8438425 TI - Prospective randomized comparison of quadruple vs triple therapy for first cadaver transplants with immediate function. PMID- 8438427 TI - Randomized controlled trial of complete steroid withdrawal in renal transplant patients receiving triple immunosuppression. PMID- 8438428 TI - Safety and efficacy of long-term cyclosporine-ketoconazole administration and preliminary results of a randomized trial. PMID- 8438429 TI - Predictors of improved outcome in second pediatric renal transplant recipients. PMID- 8438430 TI - A futures market in cadaveric organs: would it work? PMID- 8438431 TI - Renal transplantation: nifedipine for the nonstarters? A prospective randomised study. PMID- 8438432 TI - Misoprostol in renal transplantation. PMID- 8438433 TI - Role of thromboxane in the generation of allograft arteriosclerosis in chronic rejection. PMID- 8438434 TI - Ascorbic acid and alpha-tocopherol prolong rat cardiac allograft survival. PMID- 8438435 TI - Effect of nifedipine on renal haemodynamics and urinary protein excretion in stable renal transplant recipients. PMID- 8438436 TI - Influence of posttransplantation blood transfusion on kidney allograft survival: a one-center, double-blind, prospective, randomized study comparing cryopreserved and fresh red blood cell concentrates. PMID- 8438437 TI - Adhesion and homing molecules. PMID- 8438438 TI - Trial of cyclosporine vs OG37-325 in cadaveric renal transplantation: a preliminary report. PMID- 8438439 TI - New cyclosporine derivative SDZ IMM 125: in vitro and in vivo pharmacologic effects and toxicologic evaluation. PMID- 8438440 TI - One-year follow-up results of a phase I trial of mycophenolate mofetil (RS61443) in cadaveric renal transplantation. PMID- 8438441 TI - Controlled trial of RS-61443 in renal transplant patients receiving cyclosporine monotherapy. PMID- 8438442 TI - RS-61443 for treatment-resistant human liver rejection. PMID- 8438443 TI - RS-61443: rescue therapy in refractory kidney transplant rejection. PMID- 8438444 TI - Prolongation of allograft and xenograft survival with mycophenolate mofetil (RS 61443) and brequinar sodium (DUP-785). PMID- 8438445 TI - RS-61443/cyclosporine combination therapy prolongs canine liver allograft survival. PMID- 8438446 TI - Potentiation of the antiproliferative activity of brequinar sodium for murine lymphocytes by exogenous cytidine. PMID- 8438447 TI - Brequinar sodium suppresses liver allograft rejection and induces permanent tolerance in the rat. PMID- 8438448 TI - Correlation of the in vitro and in vivo immunosuppressive activity of brequinar sodium. PMID- 8438449 TI - Effects of brequinar sodium on cynomolgus monkeys: immunosuppression and pharmacokinetics. PMID- 8438450 TI - Rapamycin treatment prevents and/or erases sensitization and abrogates accelerated rejection of vascularized organ allografts. PMID- 8438451 TI - Influence of rat strain on rapamycin's kidney effects. PMID- 8438452 TI - Rapamycin in a porcine renal transplant model. PMID- 8438453 TI - Effect of rapamycin on induction of unresponsiveness in ALS-treated, marrow injected mice. PMID- 8438454 TI - Rapamycin reverses acute heart, kidney, and pancreas allograft rejection and prevents accelerated heart allograft rejection in the rat. PMID- 8438455 TI - Studies of the T-cell receptors of T cells recognizing the same HLA molecule. PMID- 8438456 TI - Rapamycin's long-term effects on humoral and cellular immune responses in the rat. PMID- 8438457 TI - In vivo use of rapamycin suppresses neither IL-2 production nor IL-2 receptor expression in rat transplant model. PMID- 8438458 TI - Interaction between rapamycin and pretransplant blood transfusions in rat heterotopic heart transplantation. PMID- 8438459 TI - Rapamycin effects on immunologic reconstitution. PMID- 8438460 TI - Rescue therapy with rapamycin blocks an ongoing process of heart allograft rejection. PMID- 8438461 TI - T-cell alloreactivity to major histocompatibility complex peptides in context of self major histocompatibility complex. PMID- 8438462 TI - Establishment of rejection therapy with deoxyspergualin by multicentral controlled clinical studies in renal recipients. PMID- 8438463 TI - Human interleukin-2-IgM heavy-chain-fusion proteins are cytotoxic for cells expressing the IL2 receptor. PMID- 8438464 TI - Interference with intracellular carbohydrate processing by castanospermine prolongs heart allograft survival. PMID- 8438465 TI - Immunosuppressive effects of leflunomide in a cardiac allograft model. PMID- 8438466 TI - Leflunomide, a novel immunomodulatory agent: in vitro analyses of the mechanism of immunosuppression. PMID- 8438467 TI - Analysis of T-cell receptor V beta gene usage in T cells infiltrating human renal allografts. PMID- 8438468 TI - Effects of rapamycin on renal microsomal P-450 systems in the rat. PMID- 8438469 TI - Effects of immunosuppressive therapy on the rat aortic allograft model. PMID- 8438470 TI - DAB486-IL-2 (IL-2-toxin) in combination with low-dose RS-61443 (mycophenolate mofetil) prolongs murine thyroid allograft survival. PMID- 8438471 TI - Synergistic effect of cholera toxin with cyclosporine and azathioprine on survival of rat renal allografts. AB - A combination of 10 mg/kg/d of AZA and 0.1 mg/kg/d of CT significantly prolonged graft survival (P < .05) over 10 mg/kg/d of AZA alone. A combination of 2.5 mg/kg/d of CyA and 0.1 mg/kg of CT given only once significantly (P < .05) prolonged graft survival over 2.5 mg/kg/d of CyA alone. PMID- 8438472 TI - Prolongation of allogeneic transplanted skin grafts and induction of tolerance by leflunomide, a new immunosuppressive isoxazol derivative. PMID- 8438473 TI - 15-Deoxyspergualin potentiates the immunosuppressive effect of cyclosporine A in a rat heart allograft model. PMID- 8438474 TI - T-cell receptor V gene segment usage of graft-infiltrating T-lymphocytes after heart transplantation. PMID- 8438475 TI - Further study of deoxyspergualin prophylaxis in living related renal transplantation. PMID- 8438476 TI - Generation of a potentially immunosuppressive rat interleukin-2 immunoglobulin M fusion molecule. PMID- 8438477 TI - Eight-year actuarial graft and patient survival of kidney transplants in highly immunized recipients pretreated with total lymphoid irradiation: a single-center experience. PMID- 8438478 TI - 15-Deoxyspergualin inhibits antibody production in mouse to rat heart transplantation. PMID- 8438479 TI - Immunosuppression of cynomolgus renal allograft recipients with humanized OKT4A monoclonal antibodies. PMID- 8438480 TI - Anti-CD4 monoclonal antibody-induced allograft survival is associated with a defect in interleukin-2-dependent T-cell activation. PMID- 8438481 TI - Selection and chimerization of a monoclonal CD4 antibody for heart transplantation. PMID- 8438482 TI - Stability of tolerance in mice generated by CD4 and CD8 monoclonal antibody treatment: cell transfer experiments. PMID- 8438483 TI - Interaction between CD4 and CD8 T cells determines graft outcome in monoclonal antibody-treated mice. PMID- 8438484 TI - Potent CD8+ CTLs detected in anti-CD4 (OKT4A) MAb immunosuppressed cynomolgus recipients with prolonged allograft survival. PMID- 8438485 TI - Anti-T cell monoclonal antibodies for immunosuppression in xenotransplantation of fetal pig pancreas in NOD mice. PMID- 8438486 TI - Devising murine models to better adapt clinical protocols: sequential low-dose treatment with anti-CD3 and anti-CD4 monoclonal antibodies to prevent fully mismatched allograft rejection. PMID- 8438487 TI - Cell migration and chimerism--a unifying concept in transplantation--with particular reference to HLA matching and tolerance induction. PMID- 8438488 TI - Differential expression of T-cell receptor-V region determinants on infiltrating T cells in rejecting and nonrejecting human kidney, liver, and heart allografts. PMID- 8438489 TI - OKT4A (a murine IgG2a anti-CD4 monoclonal antibody) in human organ transplantation: pharmacokinetics and peripheral pharmacodynamics. PMID- 8438490 TI - Use of OKT4A (a murine monoclonal anti-CD4 antibody) in human organ transplantation: initial clinical experience. PMID- 8438491 TI - CD4 monoclonal antibodies in the preclinical dog renal allograft model. PMID- 8438492 TI - Differential sensitivity to anti-LFA-1 inhibition of Th1 vs Th2 anti-minor histocompatibility antigen immune T cells after restimulation with antigen on hepatic or splenic APCs. PMID- 8438493 TI - A non-lymphocyte-depleting monoclonal antibody to the adhesion molecule LFA-1 (CD11a) prevents sensitization to alloantigens and effectively prolongs the survival of heart allografts. PMID- 8438494 TI - Monoclonal antibodies against LFA-1 and VLA-4 inhibit graft vasculitis in rat cardiac allografts. PMID- 8438495 TI - Chemically engineered bispecific antibody directed at the p55 and p75 chains of the human interleukin 2 receptor: specific high-affinity cross-linking of p55/p75 complexes and high blocking effect on IL2-induced T cell proliferation. PMID- 8438496 TI - Prophylactic use of the anti-IL-2 receptor monoclonal antibody LO-Tact-1 in cadaveric renal transplantation: results of a randomized study. PMID- 8438497 TI - Generation of rabbit anti-lymphocyte monoclonal antibodies. PMID- 8438498 TI - T-cell receptor-V alpha gene use in sequential liver allograft biopsies. PMID- 8438499 TI - Effect of monoclonal antibody on corneal graft survival across major and minor histocompatibility mismatches. PMID- 8438500 TI - Conceptual aspects of antigen presentation across a species barrier. PMID- 8438501 TI - H-2 class I-restricted recognition of allogeneic class I peptides. PMID- 8438502 TI - Major histocompatibility complex-expressing human cardiac myocytes are not the direct target of host cardiac-infiltrating cells: evidence for a prominent role of the indirect pathway in human cardiac allograft rejection. PMID- 8438503 TI - Comparison of the repertoire of T-cell lines and clones specific for minor histocompatibility antigens derived from immunized mice and from mice developing a graft-versus-host reaction. PMID- 8438504 TI - Passenger leukocyte effect not mediated by interstitial dendritic cells. PMID- 8438505 TI - Lymphocyte culture from routine endomyocardial biopsies: lack of clinical or pathological correlations. PMID- 8438506 TI - Safe motherhood: listening to women. PMID- 8438507 TI - Drug resistance of Mycobacterium tuberculosis in Karachi, Pakistan. AB - We determined the primary and secondary resistance of isolates of M. tuberculosis to the standard antituberculous drugs in Karachi (Pakistan). Primary resistance to one or more anti-tuberculous drugs was found in 17% of 123 isolates of M. tuberculosis (obtained from patients with no history of previous treatment for tuberculosis). Secondary resistance was found in 36% of 33 isolates (obtained from individuals who had received anti-tuberculous treatment in the past). The drug to which organisms were most commonly resistant was isoniazid (11% primary resistance, 30% secondary resistance). Fifteen per cent of isolates obtained from previously-studied patients showed secondary resistance to rifampicin. We discuss the importance of these findings for tuberculosis treatment and control. PMID- 8438508 TI - Use of steroids in dermatological emergencies. PMID- 8438509 TI - Paederus (Nairobi fly) vesicular dermatitis in Tanzania. AB - Four cases of dermatitis following contact with insects of the genus Paederus are described. The insects are known in East Africa as Nairobi fly and cause an acute, painful toxic epidermolysis when crushed on skin. Local clinicians are familiar with the condition, but it should also be borne in mind as a cause of unusual skin lesions in visitors returning from East Africa. PMID- 8438510 TI - Surveys of antimicrobial sensitivity. PMID- 8438511 TI - Endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy: experience in the Sudan. AB - Over a 5 year period 626 endoscopic retrograde cholangiopancreatography (ERCP) examinations were attempted in Khartoum, Sudan. The relevant duct was successfully cannulated and visualized in 94% of cases of biliary tract disease and in 73% of cases of pancreatic disease. This was due to the large number of cases with advanced pancreatic cancer. The commonest abnormal finding was stones in the biliary tree in 214 cases (35% of all cases). Cholangiocarcinoma was seen in 18 cases, pancreatic cancer in 64 cases, chronic pancreatitis in 48 cases and periampullary carcinoma in 20 cases. ERCP was considered normal in 100 cases. Endoscopic sphincterotomy (EST) was performed in 48 cases; 44 had common duct stones. ERCP and EST are feasible and useful procedures in a developing country. However they are expensive and should be carried out in referral centres. PMID- 8438512 TI - Volvulus of the sigmoid colon--a re-appraisal. PMID- 8438513 TI - Malaria: impact of a standardized protocol on inpatient management. PMID- 8438514 TI - Malaria and prophylaxis among expatriate aid workers in the Solomon Islands: 1987 to 1992. PMID- 8438515 TI - Analysis of 31 consecutive cases of ovarian carcinoma in Nigeria. PMID- 8438516 TI - Antibiotic susceptibility of urinary pathogens from inpatients in Kumasi, Ghana. PMID- 8438517 TI - Antibiotic sensitivities of beta-haemolytic streptococci isolated in Barbados. PMID- 8438518 TI - Perinephric abscess presenting as acute peritonitis. PMID- 8438519 TI - Tuberculous abdominal sinuses and HIV diseases. PMID- 8438520 TI - Reducing perinatal mortality. PMID- 8438521 TI - Lighting the operating field with a vehicle's headlight. PMID- 8438522 TI - Letter from ... Malawi: the first year of the College of Medicine of the University of Malawi. PMID- 8438523 TI - Mesenteric fibromatosis presenting as ovarian tumour. PMID- 8438524 TI - Primary tuberculous ulcer of the tongue. PMID- 8438525 TI - Vaginal calculus. PMID- 8438526 TI - Two cases of cephalic tetanus. PMID- 8438527 TI - An unusual foreign body in the eye. PMID- 8438528 TI - A health district as the operational unit for primary health care. PMID- 8438529 TI - Organizational design and the district health team. PMID- 8438530 TI - Radiation damage of fluorinated organic compounds measured by parallel electron energy loss spectroscopy. AB - The sensitivity of fluorinated organic compounds to radiation damage in the electron microscope was measured by electron energy loss spectroscopy (EELS). Five classes of molecules were investigated with fluorine atoms situated on: (1) an aliphatic chain, (2) an aromatic ring, (3) a trifluoromethyl group on an aromatic ring, (4) a trifluoromethyl group on a heterocyclic ring, and (5) a trifluoromethyl group next to a carbonyl group. The damage dose for fluorine loss was found to depend strongly on the position of the fluorine atoms and on specimen temperature. For poly-substituted fluorine on an aliphatic chain, approximately half of the fluorine was retained at doses in excess of 10(7) e/nm2. At room temperature molecules containing trifluoromethyl groups on aromatic or heterocyclic rings were much more sensitive to fluorine loss than compounds having fluorine substituted directly on the rings. This behavior is consistent with the relatively low chemical stability of the trifluoromethyl group in these structures. The rapid loss of fluorine at low electron doses (approximately 10(4) e/nm2) in the trifluoromethyl aromatic compounds was reduced several orders of magnitude by cooling the specimen to liquid-nitrogen temperatures. An understanding of how specific types of fluorinated compounds suffer damage under the electron beam will be important in their potential application as biochemical or pharmacological probes. PMID- 8438531 TI - Two approaches to motion analysis of the ultrasound image sequence of carotid atheromatous plaque. AB - It has been observed, with a sequence of ultrasonic images, that a significant number of carotid atheromatous plaques moved under the influence of cardiovascular forces. The aim of this project was to analyse the movement of the heterogeneous and homogeneous plaques using both the discrete approach and the continuous approach. In order to verify that the movement of plaque is not due to the movement of the transducer or the respiration of the patient, global movement estimation was also carried out. Experimentation on an artificial image sequence showed that both approaches can track the target accurately. These approaches were then applied on clinical image sequences and the results showed that carotid plaque was locally moved as a result of the momentum transfer rather than the global movement of the surrounding normal tissue. PMID- 8438532 TI - A review of the physical properties and biological effects of the high amplitude acoustic field used in extracorporeal lithotripsy. AB - Extracorporeal shockwave lithotripsy (ESWL) has now been used for more than a decade in the treatment of urinary stone disease. During this period there has been a wide range of studies on the physical properties of the high-amplitude focussed fields used in ESWL and the biological effects of exposure to such fields, including their ability to fragment hard concretions. These studies form a distinct body of knowledge whose relevance to the broader literature on biological effects from lower amplitude exposures has yet to be fully evaluated. This review attempts to present the main results of biological-effects studies in ESWL along with what is known of the physical properties of lithotripsy fields with the aim of assisting this evaluation. In general, the reported biological effects of lithotripsy fields are compatible with those that have been observed at those lower amplitudes of focussed pulsed ultrasound in which transient cavitation is the dominant mechanism of interaction. The relatively large amplitudes and low frequencies in ESWL, however, make it a more potent generator of transient cavitation than most other forms of medical ultrasound. Biological effects studies with lithotripsy fields may, therefore, be expected to extend our understanding of the nature of transient cavitation and, in particular, its effects in mammalian tissue. PMID- 8438533 TI - [Solidarity and subsidiary aspects. Their association in social health insurance]. PMID- 8438535 TI - [Legal medicine aspects of current abuse potential]. AB - Abuse is defined as use of a thing, which deviates from the original use and its purpose resp. in qualitative as well as quantitative manner. The task of the forensic medicine is to evidence the abuse and the misused substance resp. in order to find a basis for the judgement of the ability of the offenders guilt. The potential of abuse of several psychotropic drugs and their proof with its possibilities and limitations are described. PMID- 8438534 TI - [Life expectancy of the drug addict]. AB - The exact characterization of the epidemiology of drug-related mortality demands investigations of cross-sectional dates and the pursuit of trends under scientifically correct conditions. At the moment the possibilities of research in this field are limited. This is the reason why conclusions concerning the life expectancy of drug-addicts should be drawn with caution. Although systemic studies are not available and--for different reasons--cannot be expected in the FRG few sample surveys do exist which may be considered indicative of certain trends in mortality. Besides the Netherlands the FRG has become the most important market characterized by a rapid increase in illegal drug traffic. The number of drug-related deaths dramatically rises and the elder age-groups are increasingly concerned with the age-group from 20 top 30 years displaying a significantly increased mortality in connection with drug abuse. The epidemiologic development described so far is supposed even to be aggravated because the i.v.-drug-addicts are at high risk to acquire a hepatitis or HIV infection. PMID- 8438536 TI - [Medicinal and illicit drug effects on automobile drivers in the Munster area 1980 to 1989. A retrospective study]. AB - Chemical and toxicological investigations were carried out on blood and/or urine samples from 367 cases from the years 1980 to 1989 when there was a suspicion of driving under the influence of medication or drugs. During the investigation period no increase in the number of cases was found. This shows a clear discrepancy to the increasing misuse of medication and drugs an subsequently poses a substantial problem in traffic medicine. In 72% of the cases substances were found, which are capable of reducing the psychic and physical competence, most commonly benzodiazepines, barbiturates and opiates. In some cases these substances were present in overdose levels. The proportion of female road-users was 20% of the total. The age group between 20 and 29 was the most strongly represented rein both men and women. PMID- 8438537 TI - [Psychiatric aspects of surgical therapy in advanced age]. AB - Nowadays, in medical treatment of the aged, anaesthesiology and surgical techniques permit extensive operative interventions, whereby there ist no given age limit. Apparently, possible psychic problems which often occur in old age play no role; publications in this area are scarce. Very little research has been carried out concerning the problem of patient's consent for the operation, the risks involved in anaesthesia and operation which are probably increased by brain deficiency, and the patient's reduced ability to cooperate in rehabilitation. So far, there are many questions but few answers. PMID- 8438538 TI - [Homicide crimes in hospitals]. AB - Report of some cases of willful homicide in hospitals of the former GDR. In no case the patient has wished his death. Besides compassion the cause of the homicide was a large carefully expense and in two cases the attempt to prove the incapability of the competent doctor. The patients were only means to an end. All the cases are discovered by the great number of obscure death. PMID- 8438539 TI - [The relevance of autopsy for insurance carriers]. AB - By means of a retrospective study with an analysis of the data of 12,743 postmortem examinations over a period of 10 years 630 autopsy cases have been ascertained which had a connection to an insurer. Considerable differences in the reaction and behaviour in the event of damage have been found between public and private insurers. In the course of preliminary investigations by professional/trade associations or pension offices in general an immediate and consistent reaction for this group of insured persons--which has been recorded "purely accidentally"--is to be observed through initiating or analysing of postmortem investigations. Quite in contrast to these findings private insurers to only a small percentage made use of their contractual possibilities of a postmortem control and--if at all--mostly delayed, especially in those cases where the costs of such an investigation were to be debited to the insurer's account. In most cases private insurers made use of the results of postmortems by scientific organisations, courts or professional associations. According to the results of an examination following the rules of forensic medicine of postmortem findings an insurance contract conditions, in more than 50 p. c. of the cases the medical preconditions for the performance of the insurance contract had to be denied. A critical comment should follow: in quite a number of undisclosed cases a regulation of accident and life insurance claims is carried through in which unfounded decisions are taken without any postmortem controls. PMID- 8438540 TI - Prevalence of pleurisy and pneumonia in pigs in Northern Ireland (1969-1989). AB - A database of condemnation data from abattoirs was combined with a meteorological database to investigate the relationship between the prevalence of pleurisy and pneumonia in pigs in Northern Ireland and prevailing weather conditions. Between 1969 and 1989 three significant trends were found in the occurrence of condemnations due to pleurisy and pneumonia, and significant correlation coefficients were found between the percentage condemnations and air temperature. PMID- 8438541 TI - Development of a sperm zona pellucida binding assay for bull semen. AB - Assays based on sperm zona pellucida binding have been developed as diagnostic tests to predict the fertilisation potential of human spermatozoa. The aim of this study was to establish a similar assay for bull sperm. The results showed differences between established fertile bulls in the relative numbers of sperm cells bound to the zona pellucida of a batch of oocytes. These differences suggest that there may be a relationship between the sperm zona pellucida binding capacity and the fertility of bulls. PMID- 8438542 TI - Failure to publish syndrome. PMID- 8438543 TI - Dangerous dogs. PMID- 8438544 TI - Otitis media in suckler calves. PMID- 8438545 TI - Suspected adverse reaction surveillance scheme 1991: summary of results. PMID- 8438546 TI - Rhodococcus equi infection in foals: a report of an outbreak on a thoroughbred stud in Zimbabwe. AB - Twenty-four foals were confirmed to be infected with Rhodococcus equi on a private stud in Zimbabwe over a two-year period. Six mares had foals which were affected in each of the two years. All the foals were febrile and early cases were detected by this pyrexia. Bronchopneumonia was only clinically detectable in advanced cases. In spite of energetic hygiene measures relating to pasture and housing management, the incidence was higher in the second year (23 per cent of foals born) than in the first (15 per cent of foals born). The mean age of the foals was significantly greater in the second year. The immunological status of some of the foals was obtained from zinc sulphate turbidity tests performed at 24 hours old and all the affected foals so tested were considered to have had effective colostral transfer. Clinically, affected foals showed pyrexia, tachypnoea and tachycardia and many had a scanty purulent nasal discharge. Only one animal had diarrhoea which was attributed to enteric infection with R equi. Diagnosis was confirmed by clinical examination, culture of the organism from tracheal aspirates and thoracic radiography and was supported by significant elevations of plasma fibrinogen and platelet and neutrophil counts in all cases. Anaemia was not a major finding in any case. Rifampicin and erythromycin were administered per os and weight-related doses were continued until plasma fibrinogen and the absolute neutrophil and platelet counts had been persistently normal for two weeks. Supportive radiography was obtained in some cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8438547 TI - Acute lead poisoning in a beef herd associated with contaminated silage. PMID- 8438548 TI - Spina bifida in lambs. PMID- 8438549 TI - Anomalous thoracic venous and arterial patterns in a sheep. PMID- 8438550 TI - Repair of ventral metrocele (gravid) in a goat. PMID- 8438551 TI - Certificate in animal welfare. PMID- 8438552 TI - Firing and snoring. PMID- 8438553 TI - Vero cytotoxin-producing Escherichia coli in a herd of dairy cattle. PMID- 8438554 TI - Neuronal ectopic masses induced by prenatal irradiation in the rat. AB - Ectopic neuronal masses below the subcortical white matter were seen in the brains of postnatal rats after 200 cGy irradiation at embryonic day 14. In contrast with the laminated organisation of the cortex located above the subcortical white matter, the ectopic masses were formed of confluent nodules composed of pyramidal and non-pyramidal neurons distributed at random, with no laminar organisation. Afferent and efferent fibres to/from the ectopic masses running together with fibres passing the subcortical white matter indicated that the ectopic masses were heavily connected to neighbouring structures. Examination of irradiated embryos revealed that the ectopic masses originated from ectopic periventricular rosettes, composed of germinal cells, which were formed shortly after irradiation. Neuronogenesis in these rosettes did not follow an inside-out gradient, as seen in the laminated cortex; however, early-generated neurons predominated in the external regions, whereas late-generated neurons were mainly located in the middle and internal regions of the ectopic masses. PMID- 8438555 TI - Scanning electron microscopy of human lumbar vertebral trabecular bone surfaces. AB - Trabecular bone from fourth lumbar vertebral bodies of 30 autopsy subjects (18 male and 12 females, 30-91 years of age) was investigated using surface mode scanning electron microscopy. In the younger individuals, proper coupling of formation and resorption appeared to have maintained both the bone mass and the shape and structural integrity of the trabecular elements. In elderly individuals, including osteoporotics, irregularities and uncoupling of these activities brought about a loss of bone and a disruption of trabecular structure. Distinct resorption patterns (lateral and vertical) are responsible for trabecular thinning and removal of structural elements. Irregularities in the formative process in old age may account for the compensatory thickening and changes in shape and texture of trabecular elements. The mechanisms involved in the occurrence of microfractures and the fate of disconnected elements were also identified. An increased proportion of arrested mineralizing fronts is found in older individuals and in frank osteoporotics. Resorption may occur through osteoid and arrested mineralizing fronts, as well as through resting, fully mineralized surfaces. PMID- 8438556 TI - Widespread distribution of nuclear androgen receptors in the basal cell layer of the normal and hyperplastic human prostate. AB - The role of the basal cell layer in organogenesis, epithelial renewal and development of benign prostatic disorders is largely unknown. The objective of the present study was to investigate whether or not basal cells express the nuclear androgen receptor (AR). Computer-assisted image analyses of immunohistochemical double stainings were performed to localize AR and basal-cell specific cytokeratins in identical sections. The results showed that the basal cells express nuclear AR widely in normal and hyperplastic conditions. When compared with the staining intensities detected in secretory luminal cells, the receptor was most frequently expressed at lower levels in basal cells, which may exhibit strong AR immunoreactivity focally. Basal cells with increased AR expression were most frequently detected in hyperplastic lesions including post atrophic and atypical hyperplasia. The presence of nuclear receptors for both androgens and oestrogens or progestins in basal cells may indicate that these cells are targets of the hormonal imbalance which has frequently been implicated in the aetiology of benign prostatic hyperplasia. PMID- 8438557 TI - Amyloid stroma in meningiomas. AB - Twenty-three cases of meningiomas with psammoma bodies (PBs) and 15 without PBs have been studied using histochemical, ultrastructural and immunohistochemical methods for amyloid. Amyloid was found in all cases showing PBs and in only 5 cases in the group devoid of PBs. Meningiomas may contain amyloid in their stroma. PMID- 8438558 TI - Diagnosis of cardiac thrombosis in patients with atrial fibrillation in the absence of macroscopically visible thrombi. AB - Cardiac thrombosis due to atrial fibrillation (AF) has been recognized as the most common cause of cerebral embolism. However, sometimes no macroscopic thrombus is found at autopsy in the heart of a victim of this type of cerebral embolism. We investigated morphological changes in the left atrial endocardium of 31 patients (including 21 cases with AF) who had died of cerebral embolism. "Rough endocardium" (RE) seen macroscopically provided evidence for the existence of atrial thrombosis. The RE that appeared in AF cases was due to a granular and wrinkled appearance of the endocardium associated with oedematous and fibrous thickening. Fibrin-thread deposits were also always distinguishable. Mural thrombi and oedema with neutrophil infiltration in the subendocardium could be seen under the microscope. Small areas of endothelial denudation and thrombotic aggregations were commonly observed by scanning electron microscopy (SEM). These SEM lesions were significantly more frequent in cases with AF than in controls (P < 0.001). The diagnostic success rate for atrial thrombosis among cases with AF increased from 33.3% to 81% when thrombi proven by histological investigation of the areas with RE were added. Left atrial RE may be an anatomically relevant finding for the existence of atrial thrombosis with AF, when the thrombosis cannot be detected upon gross observation at autopsy. PMID- 8438559 TI - Cytogenetic study of botryoid rhabdomyosarcoma of the uterine cervix. AB - We report a case of sarcoma botryoides of the uterine cervix occurring in a 19 year-old woman. By light microscopy the tumor showed round and spindle cells with hyperchromatic nuclei and, focally, a cambium layer subjacent to the surface epithelium and surrounding endocervical glands. Strap-shaped cells with and without cross-striations and small foci of immature cartilage were also present. Immunohistochemical studies showed positive staining within the tumor cells for myoglobin, desmin, vimentin, muscle-specific actin and CD56. By electron microscopy, tumor cells showed cytoplasmic filaments in an alternating pattern of thick and thin filaments. Chromosomal analysis demonstrated deletion of the short arm of chromosome 1, and trisomies 13 and 18. To our knowledge, this is the first reported case of sarcoma botryoides of the endocervix with chromosomal analysis. PMID- 8438560 TI - The tobamovirus capsid protein functions as a host-specific determinant of long distance movement. AB - The tobamoviruses, tobacco mosaic virus (TMV) and Odontoglossum ringspot virus (ORSV), differ in the range of plant species that each can systemically infect. Both viruses systemically infect Nicotiana benthamiana similarly, but differ in the ability to systemically infect tobacco (N. tabacum). ORSV is confined to the inoculated leaves of N. tabacum, whereas TMV causes a rapid systemic infection. Genetic chimeras were created to identify viral genes involved in specific interactions in long-distance movement in N. tabacum. In N. tabacum, a chimera expressing the ORSV 30-kDa protein exhibited a reduced rate of cell-to-cell spread, similar to that of ORSV, and, also like ORSV, was deficient in systemic invasion, implying a relationship between the rates of cell-to-cell and long distance movement. However, a TMV chimera expressing the ORSV capsid protein gene spread cell to cell similarly to TMV, but was deficient in long-distance movement and systemic infection. These data suggest that tobamovirus capsid protein(s) may be required to interact with host components in a specific manner to allow efficient long-distance movement, and the ORSV capsid protein did not function in this manner in tobacco plants. PMID- 8438561 TI - Self-limiting infection by int/nef-double mutants of simian immunodeficiency virus. AB - Simian immunodeficiency virus (SIVmac) infectious for rhesus monkeys was altered by site-directed mutagenesis of genes influencing in vivo replication and persistence with the long-term goal to develop attenuated lentiviruses with limited replication capacity in vivo. Double mutants of SIVmac (termed delta-int 1 to 3) were generated by introducing frameshift and deletion mutations into the nef gene and into the pol gene region coding for the integrase protein. Delta int/delta-nef viruses formed after transfection of CD(4+)-lymphocyte cell lines were unable to establish sustained replication. In contrast, both wild-type SIVmac and mutant SIVmac delta-nef (coding for a truncated NEF protein and a wild type INT protein) replicated continuously and at a comparable rate. However, a transient and self-limiting infection of the C8166 T-cell line was observed subsequent to transfection of double mutant proviruses into HeLa-tat-III cells. Viruses attenuated by int/nef-double mutation were able to enter the T-cells, initiate synthesis of viral DNA as shown by PCR amplification of closed circular episomes, and express viral antigens in infected cells as demonstrated by immunocytochemical staining. Integration of the int mutant viruses into the chromosome was completely inhibited. Episomal viral DNA was detectable in the infected cells for up to 2 weeks, after which it disappeared. Thus, SIVmac attenuated by int and nef mutation established a transient infection of permissive cells resulting in the expression of viral antigen from episomal viral DNA over a limited period of time. PMID- 8438562 TI - Directed mutagenesis of a Sindbis virus pathogenesis site. AB - The E2 glycoprotein gene of Sindbis virus contains three neutralizing antigenic sites, and examination of monoclonal antibody (MAb) escape mutants of one of these, the E2c site, has suggested an association of the E2c domain with determinants of virulence in neonatal mice. Codons associated with the E2c site, E2 62, 96, and 159, were subjected to site-directed mutagenesis generating a library of 25 viable virus mutants containing different amino acids at these loci. The mutants were assessed for their ability to bind E2a, E2b, and E2c MAbs in an enzyme-linked immunosorbent assay, to induce fatal disease in neonatal mice following subcutaneous or intracranial inoculation and to compete with wild-type virus for binding to unfractionated neonatal mouse brain cells. None of the substitutions affected binding of E2a or E2b MAbs, and decreased binding to E2c MAbs was correlated with decreased virulence in neonatal mice. However, correlation of decreased virulence and binding to E2c MAbs with decreased competition for wild-type virus binding to mouse brain cells was not observed. The effect of mutation on E2c binding and virulence varied widely depending on the locus and the specific substitution, suggesting strategies for the molecular design of live virus vaccines which select both locus and codon to maximize attenuation and minimize the potential for reversion to virulence. PMID- 8438563 TI - Biosynthesis of reovirus-specified polypeptides: identification of regions of the bicistronic reovirus S1 mRNA that affect the efficiency of translation in animal cells. AB - The reovirus S1 gene cDNA was systematically altered by site-directed mutagenesis in an attempt to identify regions important in determining the relative efficiency of translation of the two open reading frames of the bicistronic S1 mRNA. The synthesis of the minor capsid protein sigma 1 encoded by ORF1, extending from AUG14 to UGA1424, and the synthesis of the nonstructural protein sigma 1NS encoded by ORF2, extending from AUG75 to UAG432, were examined in transfected COS cells. Deletion of the 5'-untranslated region upstream of ORF1 AUG14 did not significantly affect either the relative amount, or the ratio, of sigma 1 and sigma 1NS synthesized. Creation of a strong context ORF1 initiation site by substitution of 5'-untranslated region nucleotides flanking AUG14 likewise did not affect sigma 1 synthesis, but sigma 1NS synthesis from ORF2 was decreased about twofold relative to wild-type S1 mRNA. The amount of sigma 1NS synthesis was increased less than twofold either by elimination of the ORF1 AUG14 initiation codon or by termination of sigma 1 synthesis shortly after initiation from AUG14. No sigma 1 synthesis was detected when the ORF1 AUG14 was mutated to a UUG14 codon. When ribosomes which initiated translation at AUG14 were frameshifted at the next codon after AUG14, elongation occurred with comparable efficiency in the sigma 1NS ORF2 and in sigma 1 ORF1. No sigma 1NS synthesis was detected when the ORF2 AUG75 was mutated to an CUG75 codon, and this mutation did not affect the amount of sigma 1 synthesis. sigma 1NS synthesis was not affected by truncation of the 3'-untranslated region or premature termination of sigma 1 synthesis shortly after the ORF2 UAG432. However, truncation of the ORF2 5' untranslated region at either 6 or 36 nt following the ORF1 AUG14 significantly increased the efficiency of sigma 1NS synthesis. These results indicate that the region of the S1 mRNA immediately downstream of the sigma 1 ORF1 initiation codon AUG14 but well upstream of the sigma 1NS ORF2 initiation codon AUG75 plays a major role in determining the relative efficiency of synthesis of sigma 1 and sigma 1NS from the reovirus bicistronic s1 mRNA. PMID- 8438564 TI - A conditional mutant of vRel containing sequences from the human estrogen receptor. AB - The mechanism by which the v-rel oncogene of the avian Rev-T retrovirus transforms chicken spleen cells is not known. We have created v-rel mutants that show conditional properties by fusing sequences encoding the ligand-binding domain of the human estrogen receptor (ER) in-frame at the 3' end of the v-rel oncogene. Two vRel-ER fusion proteins showed estrogen-dependent subcellular localization in chicken embryo fibroblasts (CEF): vRel-ER proteins were located in the cytoplasm of CEF in the absence of estrogen and were located in the nucleus of CEF in the presence of estrogen. Wild-type vRel was located in the nucleus of CEF in the presence or absence of estrogen. Mobility shift assays using extracts from infected CEF showed that the ability of vRel-ER to bind DNA was also dependent on estrogen. However, the ability of vRel-ER to repress transcription from kappa B site-containing promoters was not dependent on estrogen. Finally, we were able to isolate a vRel-ER-transformed avian spleen cell line whose growth is dependent on estrogen; this indicates that a vRel function is needed for both the initiation and the maintenance of the transformed state. The vRel-Er protein may be useful for determining genes controlled by vRel. PMID- 8438565 TI - Transcomplementation of VIF- HIV-1 mutants in CEM cells suggests that VIF affects late steps of the viral life cycle. AB - The vif gene of HIV-1 has previously been claimed to be essential for the ability of cell-free virus preparations to infect cells. Here we report that the CEM T cell-line, stably transfected with and expressing vif, supports the replication of vif- HIV-1 viruses to the same extent as wild-type HIV1. Cell entry and early replication stages are the same for vif- and vif+ HIV-1 passaged in CEM, as measured both by a PCR-based cell entry assay and by fusogenic potential. These findings indicate that vif does not affect viral infectivity on CEM cells, but seems to act at a later stage of virus replication/maturation. We also show that the VIF proteins of two different HIV-1 strains can transcomplement different vif HIV-1 mutants. PMID- 8438566 TI - Synthesis of the putative red clover necrotic mosaic virus RNA polymerase by ribosomal frameshifting in vitro. AB - The red clover necrotic mosaic virus (RCNMV) genome is split between two single stranded RNA species termed RNA-1 and RNA-2. RNA-1 directs the synthesis of 88 kDa (p88), 57-kDa (p57), 37-kDa (p37), and 27-kDa (p27) polypeptides and RNA-2 a 35-kDa (p35) polypeptide in vitro. The coding order of the RNA-1 products was determined to be 5'-p27-p57-p37-3'. Antibodies to synthetic peptides representing the carboxyl terminal portions of p27 and p57 immunoprecipitated their respective polypeptides in addition to p88, suggesting that p88 is a fusion protein. A frameshift heptanucleotide sequence element has been identified in RCNMV RNA-1. In addition, a stable stem-loop secondary structure adjacent to the heptanucleotide sequence is predicted. Together, these sequence elements suggest that a ribosomal frameshifting event occurs which allows translational readthrough of the p27 open reading frame into the p57 open reading frame, generating the observed p88 product. An RNA-1 expression construct fusing the p57 and the CP open reading frame was engineered to investigate the ribosomal frameshifting event. CP antibodies immunoprecipitated a fusion protein of the predicted size containing the carboxyl portion of CP. Site-directed mutagenesis of the frameshift element indicates that in vitro, p88 can also be expressed alternatively by suppression of an amber termination codon. Based on these data, we propose that the putative RCNMV RNA polymerase is an 88-kDa polypeptide expressed by a ribosomal frameshifting mechanism similar to those utilized by retroviruses. PMID- 8438567 TI - Intracellular transport and virion incorporation of vpx requires interaction with other virus type-specific components. AB - Viral protein X (vpx) is a virion-associated HIV-2/SIV accessory protein that enhances viral infectivity and replication in natural target cells. To investigate whether other viral components affect its biosynthesis, subcellular localization, and virion incorporation, we expressed HIV-2 vpx in a mammalian cell system and examined its transport and packaging requirements using an in trans complementation assay. The complete vpx coding region of HIV-2ST was placed under the control of a high-efficiency promoter system (SR alpha) which contained both an SV40 promoter/enhancer region and R/U5 elements of the HTLV-1 LTR. Following transfection of Cos-1 cells, this construct (pSR alpha-vpx) facilitated high level expression of vpx, as demonstrated by Western blot analysis of transfected cell lysates. Moreover, indirect immunofluorescence analysis revealed an intense vpx staining pattern distributed evenly throughout the cytoplasm of transfected cells. This distribution differed markedly from cells expressing wild type HIV-2 in which vpx localized to the inner surface of the plasma membrane. To determine whether other HIV components were required for this surface localization, we expressed vpx in the context of replication competent HIV-1 and HIV-2 proviruses. Following cotransfection with a vpx-deficient HIV-2 provirus (pXM7), eukaryotically expressed vpx targeted to the plasma membrane and colocalized with HIV-2 p27 gag in a pattern indistinguishable from wild-type HIV 2. Moreover, progeny virions from cotransfected Cos-1 cells contained wild-type amounts of vpx protein, demonstrating that vpx could be efficiently packaged in trans. Under the same experimental conditions, cotransfection of vpx with wild type HIV-1 (pHXB2) and with vpr-deficient HIV-1 (pR2) failed to result in detectable cell surface targeting or virion incorporation of vpx despite its high level cellular expression. These results demonstrate that efficient intracellular transport and packaging of vpx require interaction with other type-specific virus components. PMID- 8438568 TI - Preliminary X-ray data analysis of crystalline cowpea chlorotic mottle virus. AB - Crystals of cowpea chlorotic mottle virus (CCMV) that diffract X-rays to 3.1 A resolution were grown in a succinate-PEG solution buffered at pH 3.3. The crystals are in space group P2(1)2(1)2(1) with unit cell dimensions of a = 381.26 A, b = 381.26 A, and c = 408.59 A. Four particles occupy the unit cell, placing a single virion in the crystallographic asymmetric unit. Diffraction intensities measured from 196 films collected at the Cornell High Energy Synchrotron Source accounted for 55% of the theoretically possible data to 3.2 A. Unit cell dimensions and rotation function analyses of the X-ray data revealed that the particles were organized in a pseudo-tetragonal relationship with the pseudo fourfold axis along the crystal c axis. Analysis of electron micrographs of two dimensional crystals of CCMV revealed a remarkable similarity between these and planes of particles perpendicular to the crystallographic c axis in the three dimensional crystal. PMID- 8438569 TI - Morphogenic capabilities of human immunodeficiency virus type 1 gag and gag-pol proteins in insect cells. AB - To determine the interaction between the gag precursor and the viral protease and to confirm the role of gag precursor in formation of human immunodeficiency virus type 1 particles, the gag and protease encoding regions of a proviral genome with mutations at the site between p17 and p24 or p24 and p15 were expressed by recombinant baculoviruses under the transcriptional control of the strong polyhedrin promoter. Western blot analyses of the expressed products of p17-p24 mutated viruses revealed that both 41- and 55-kDa proteins were synthesized. However, free p24, p17, and the other smaller cleavage products (p9, p6) could not be detected in infected insect cells. The second recombinant virus (p24-p15) synthesized not only a 55k-Da protein, but also a number of smaller products including a 40k-Da protein, p24, and p17. Examination of the insect cells infected by either of these two recombinant viruses by electron microscopy failed to detect any gag particle formation, although some irregular membrane protrusions and profound distortions of the cell surface were clearly visible in the cells infected with recombinant mutant p17-p24 virus, but not with recombinant p24-p15 mutants. To investigate the morphogenic capability of the gag pol fusion protein, a mutant gag-pol gene containing an inactive protease as well as a modified gag-pol gene lacking the frameshifting activity were expressed in insect cells. While the inactive protease mutant was capable of forming immature particles that were secreted, the frameshifting mutant synthesized only an aberrant form of gag particles with a large radius of curvature in lieu of spherical particles. However, when this mutant was expressed in insect cells in the presence of a truncated gag protein with M(r) of 46 kDa (lacking only the p6 domain), normal immature particles containing both antigens were formed. PMID- 8438570 TI - In vitro differentiation of monocytoid THP-1 cells affects their permissiveness for HIV strains: a model system for studying the cellular basis of HIV differential tropism. AB - The prototypic macrophage-tropic HIV-1 isolate, HIV-1BaL, cannot replicate in the monocytoid cell line THP-1. After induction of differentiation by a phorbol diester, a fraction of THP-1 cells became permissive to HIV-1BaL. In contrast, this treatment decreased permissiveness for the lymphotropic isolate HIV-1LAI. Viral DNA was not synthesized in unstimulated THP-1 cells, as determined with PCR, suggesting that the block to HIV-1BaL replication in these cells occurred at an early step of the virus replicative cycle prior to or at the level of reverse transcription. Virus binding studies showed that differences in cell permissiveness for HIV-1BaL were not due to altered virus binding. Substantial amounts of HIV-1BaL bound to both undifferentiated and differentiated THP-1 cells, and this binding could not be prevented by blocking with the anti-CD4 antibody Leu3a, which did prevent the binding of HIV-1LAI to CEM T lymphoid cells. While Leu3a was very effective at preventing the infection by HIV-1LAI in CEM cells, it was less effective in preventing HIV-1BaL infection of differentiated THP-1 cells or primary macrophages. Although it is likely that molecules other than CD4 on monocytic cells can mediate binding of macrophage tropic HIV, the binding of HIV-1BaL to THP-1 cells was not sufficient for infection, because binding was the same in nonpermissive undifferentiated cells as in permissive differentiated cells. Thus, the restriction of viral replication in this model cell system occurs at some step after virion binding. Comparison of differentiated THP-1 cells with their undifferentiated counterparts may provide an approach to defining cellular determinants of HIV host range other than CD4 expression and to characterizing the incompletely defined steps of viral entry. PMID- 8438571 TI - pH-dependent pore formation in Semliki forest virus-infected Aedes albopictus cells. AB - The plasma membrane properties of Semliki forest virus-infected Aedes cells were studied using whole-cell patch-clamp recording. Cells exhibited a marked increase in membrane conductance, gm (from 0.48 +/- 0.09 nS to 14.2 +/- 10.8 nS) upon exposure to acidic pH (5.6). The membrane potential depolarized from -40.9 +/- 5.2 mV to -2.43 +/- 7.14 mV under these conditions. In uninfected cells, there was no change in gm after lowering the pH. This implies that viral fusion proteins are involved in changing the membrane properties at low pH. The increased gm in infected cells at low pH was not persistent but declined within minutes. Millimolar concentrations of calcium and zinc prevented or reverted the increase in gm. The results suggest that viral proteins, if brought to their fusogenic conformation by exposure to low pH, form unspecific pores in the residing membrane. These pores might play a role in virus entry. PMID- 8438572 TI - Interferon alpha-mediated inhibition of human immunodeficiency virus type 1 provirus synthesis in T-cells. AB - Previously, we have shown that interferon (IFN)-alpha markedly inhibits human immunodeficiency virus type-1 (HIV-1) replication in the CEM-174 lymphocytic cell line during a single replication cycle. In the present study, we demonstrate that the IFN-mediated block of HIV-1 replication is at the level of HIV-1 provirus formation. Using polymerase chain reaction and a set of primers that detects complete or nearly complete proviral DNA, HIV-1 provirus could be found as early as 5 hr after infection in CEM-174 cells and peripheral blood lymphocytes. Pretreatment of cells with 500 U/ml IFN-alpha resulted in a significant reduction in the relative levels of HIV-1 proviral DNA. The levels of HIV-1 proviral DNA in IFN-alpha-treated cells were also reduced when primers detecting the early reverse-transcripts were used, indicating that IFN interferes with the initiation of HIV-1 reverse-transcription. The inhibition of provirus formation was also observed in vitro; addition of cytoplasmic extracts from IFN-treated CEM-174 cells, but not from the control cells, resulted in inhibition of both virion associated and recombinant HIV-1 reverse transcriptase activity. These studies implicate that, when used therapeutically, IFN-alpha should limit the spread of HIV-1 infection. PMID- 8438573 TI - Defective interfering RNA-mediated resistance against cymbidium ringspot tombusvirus in transgenic plants. AB - Defective interfering (DI) RNA of cymbidium ringspot tombusvirus was cloned downstream from the bacteriophage T7 RNA polymerase promoter. In vitro synthesized RNA was biologically active when coinoculated with parental genomic RNA onto Nicotiana benthamiana plants and prevented the occurrence of apical necrosis. N. benthamiana plants were transformed with the DI RNA sequences in both the positive and negative orientations relative to the cauliflower mosaic virus 35S promoter. Integration of DI RNA sequences in the plant genome was verified using PCR amplification of DNA extracts and Northern blot analysis of RNA extracts. DI RNA-related transcripts were detected in uninfected transgenic plants, but inoculation with the parental virus induced replication of the DI RNA only in transgenic plants expressing DI RNA in the positive orientation. Transgenic plants in which DI RNA accumulated were protected from apical necrosis and death. PMID- 8438574 TI - Molecular characterization of porcine reproductive and respiratory syndrome virus, a member of the arterivirus group. AB - Porcine reproductive and respiratory syndrome virus (PRRSV)-specific cDNA clones spanning the 3' terminal 5 kb of the genomic RNA were isolated, sequenced, and used as probes for identification of PRRSV-specific RNAs. The PRRSV genome is a positive-stranded polyadenylated RNA of about 15 kb. In infected cells, a 3' coterminal nested set of six major subgenomic mRNAs could be demonstrated. Within the 3' terminal 3.5 kb of the PRRSV genome, six overlapping reading frames (ORFs) were identified, each most likely expressed by one of the subgenomic mRNAs. Amino acid sequence comparisons revealed that the most 3' terminal ORF (ORF7) encodes the PRRSV nucleocapsid protein with a calculated molecular weight of 14 kDa. It displays 44.8% amino acid identity with the capsid protein of lactate dehydrogenase-elevating virus (LDV) and 23.6% with that of equine arteritis virus (EAV). The product of ORF6, the second 3' terminal ORF, represents a putative membrane protein and exhibits 53.2 and 27.2% amino acid identity with the corresponding LDV and EAV polypeptides, respectively. Similar to EAV, ORFs 2 through 5 might encode glycosylated viral proteins. The polypeptide deduced from the most 5' ORF (ORF1b) contains two conserved domains common to EAV and coronavirus polymerases. Genome organization, strategy of gene expression, and the sequence of deduced proteins show that PRRSV belongs to the Arterivirus group of viruses. PMID- 8438575 TI - Human adenovirus serotype 12 virion precursors pMu and pVI are cleaved at amino terminal and carboxy-terminal sites that conform to the adenovirus 2 endoproteinase cleavage consensus sequence. AB - The sequence of a 1158-base pair fragment of the human adenovirus serotype 12 (Ad12) genome was determined. This segment encodes the precursors for virion components Mu and VI. Both Ad12 precursors contain two sequences that conform to a consensus sequence motif for cleavage by the endoproteinase of adenovirus 2 (Ad2). Analysis of the amino terminus of VI and of the peptide fragments found in Ad12 virions demonstrated that these sites are cleaved during Ad12 maturation. This observation suggests that the recognition motif for adenovirus endoproteinases is highly conserved among human serotypes. The adenovirus 2 endoproteinase polypeptide requires additional co-factors for activity (C. W. Anderson, Protein Expression Purif., 1993, 4, 8-15). Synthetic Ad12 or Ad2 pVI carboxy-terminal peptides each permitted efficient cleavage of an artificial endoproteinase substrate by recombinant Ad2 endoproteinase polypeptide. PMID- 8438576 TI - Reovirus protein lambda 3 is a poly(C)-dependent poly(G) polymerase. AB - Reovirus protein lambda 3 has been isolated from cells infected with two recombinant vaccinia viruses into the TK gene of which the reovirus serotype3 strain Dearing L1 genome segment under the control of the bacteriophage T7 RNA polymerase promoter, or the T7 polymerase gene itself, had been cloned. Highly purified protein lambda 3 does not transcribe double-stranded reovirus RNA into single-stranded RNA, or plus-stranded reovirus RNA into minus-stranded RNA, but it does transcribe poly(C) into poly(G). It prefers Mn2+ to Mg2+. A polymer consisting of poly(C) linked linearly to poly(U) provided template activity only for its poly(C) moiety. Protein lambda 3 forms complexes with protein lambda 1, as well as with protein lambda 2, and with both lambda 1 and lambda 2, which are sufficiently stable to be precipitated by monospecific antisera. None of these complexes are capable of transcribing either ds- or ssRNA. PMID- 8438577 TI - Multiple arginine residues within the basic domain of HTLV-I Rex are required for specific RNA binding and function. AB - The Rex protein of the type I human T-cell leukemia virus (HTLV-I) is essential for viral replication, acting post-transcriptionally to enhance the expression of unspliced and singly spliced viral mRNAs that encode the Gag, Pol, and Env virion proteins. Rex function involves its direct interaction with a complex stem-loop structure termed the Rex RNA response element (RexRE), which is located within the 3' retroviral long terminal repeat. Binding of Rex to the RexRE involves a positively charged arginine-rich domain located near the N-terminus which also functions as a nuclear localization signal. Strikingly, substitution of all seven of the arginine residues present within this domain with positively charged lysine residues exerted no adverse effect on the nuclear targeting of Rex. However, these lysine substitutions completely abrogated both Rex binding to the RexRE and Rex function. Reversion of multiple substituted lysines to arginines at specific locations within this domain was required to restore both RexRE binding and biological function to the Rex protein. Thus, while the presence of positive charge alone in this domain appears sufficient for nuclear localization of Rex, multiple arginine residues at specific sites are essential for the full expression of RNA binding and functional activity of this retroviral trans regulatory protein. PMID- 8438578 TI - Mapping of the polycistronic RNAs of tomato leaf curl geminivirus. AB - Four major transcripts from infected tomato were identified and mapped onto the monopartite genome of the geminivirus tomato leaf curl virus (TLCV). The C1, C2, and C3 ORFs are spanned by one transcript and a second internal RNA covered C2 and C3. Both these RNAs have their counterparts in the DNA A components of the bipartite subgroup of geminiviruses. The 5' ends of the virion-sense RNAs map either side of the first in-frame AUG of the V1 ORF. The 3' ends of the virion sense RNAs are coterminal and overlap with the 3' ends of the complementary-sense RNAs. All of the RNAs have transcription regulatory sequences close to their mapped termini and the presence of overlapping transcripts suggests that temporal regulation of their synthesis may occur. The translation of these polycistronic RNAs is discussed in the light of the RNA mapping data. PMID- 8438579 TI - Induction of micronuclei by HTLV-I Tax: a cellular assay for function. AB - Cellular chromosomal damage is ubiquitously seen in HTLV-I-transformed lymphocytes. It is also characteristic of cells that have been exposed to mutagens. A sensitive measurement for mutagen-induced DNA damage is the formation of micronuclei in treated cells. Because current evidence suggests that HTLV-I Tax is etiologically linked to transformation, we tested for its activity in inducing micronuclei. We show here that transfection into cells of a Tax producing plasmid rapidly induced the formation of micronuclei. This effect cooperated with that of a mutagen (mitomycin C) and was correlated with the inherent trans-activation capacity of Tax. These findings suggest that a commonly used mutagen assay could be a quick biological test for putatively oncogenic proteins. PMID- 8438580 TI - Identification of proteins encoded by avian reoviruses and evidence for post translational modification. AB - Twelve avian reovirus strain 176 proteins, 10 structural (lambda 1, lambda 2, lambda 3, mu 1, mu 2/mu 2C, sigma 1, sigma 2, sigma 3, and sigma 4), and 2 nonstructural (mu NS and sigma NS) were identified and characterized by electrophoretic analysis of purified virions and infected cell lysates. Three of the identified proteins (mu 1, mu NS, and sigma 4) have not been previously described. In pulse-chase experiments, 10 of the proteins (lambda 1, lambda 2, lambda 3, mu 1, mu 2, mu NS, sigma 1, sigma 2, sigma NS, sigma 3) were shown to be primary translation products, whereas mu 2C was shown to be a post translational cleavage product of mu 2. PMID- 8438581 TI - Bovine respiratory syncytial virus nucleocapsid protein expressed in insect cells specifically interacts with the phosphoprotein and the M2 protein. AB - The coding region of the gene for the nucleocapsid (N) protein of bovine respiratory syncytial virus has been inserted into the genome of Autographa californica nuclear polyhedrosis virus (AcNPV) using transfer vector pVL 1393. Infection of Spodoptera frugiperda cells with recombinant virus resulted in the synthesis of high levels of N protein. This protein was indistinguishable from the authentic bovine respiratory syncytial virus (BRSV) N protein by SDS-gel electrophoresis and immunoprecipitation with anti-BRSV serum. [35S]methionine labeled N protein synthesized in S. frugiperda cells was used in a protein blotting protein overlay assay for its interactions with BRSV-infected cell proteins. The N protein synthesized in S. frugiperda cells was found to specifically interact with the phosphoprotein (P) and M2 protein of BRSV but only with the P protein of human RSV. Our results suggest that the recombinant N protein produced in S. frugiperda cells could be used to determine the domains on N protein required for binding to P and M2 proteins. PMID- 8438582 TI - Analysis of sequence variation in grapevine yellow speckle viroid 1 reveals two distinct alternative structures for the pathogenic domain. AB - The nucleotide sequences of 24 full-length cDNA clones prepared from a field isolate of grapevine yellow speckle viroid 1 (GYSV 1) have been determined and compared with that of the previously published GYSV 1 sequence. A large number of sequence variations were observed, the majority of which occurred in the pathogenicity domain (P domain) of the viroid. The GYSV 1 variants could be divided into two types each containing a distinct secondary structure within the P domain. Monomeric exact-length RNA transcripts produced from individual clones belonging to both types were infectious in viroid-free grapevines and produced homogenous populations of progeny viroid in vivo. PMID- 8438583 TI - The block to HIV-1 envelope glycoprotein-mediated membrane fusion in animal cells expressing human CD4 can be overcome by a human cell component(s). AB - Membrane fusion mediated by interaction of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein with the human CD4 molecule generally requires that the CD4 be expressed on a human cell. The failure of murine or simian cells expressing human CD4 to form syncytia upon mixing with cells expressing envelope glycoprotein could not be corrected by expression of both molecules at extremely high surface levels using vaccinia virus expression vectors. Video fluorescence microscopic analysis of fluorescent dye transfer between fusing cells indicated that the block occurred at the level of membrane fusion between individual pairs of cells. To gain insight into the basis for this fusion block, we tested the ability of fluorescent probe cells expressing envelope glycoprotein to fuse with transient animal x human hybrid giant cells expressing human CD4. The hybrid giant cells were generated either by low-pH-induced fusion of vaccinia-infected cells or by CD4/HIV-1 envelope glycoprotein-mediated cell fusion. We observed that envelope glycoprotein-expressing probe cells efficiently fused with CD4 expressing animal x human hybrid giant cells, independent of whether the CD4 was originally expressed on the animal or on the human cell. Fusion did not occur with CD4-expressing giant cells derived from animal cells alone. These results indicate that the fusion block is not due to dominant inhibitory components in the animal cell. Rather, they suggest that human cells contain an additional component(s) which, when transferred to the CD4-bearing animal cell, confers the ability to undergo membrane fusion mediated by the HIV-1 envelope glycoprotein. PMID- 8438584 TI - The activity of the coat protein promoter of chloris striate mosaic virus is enhanced by its own and C1-C2 gene products. AB - DNA fragments from the bidirectional promoter region of the geminivirus chloris striate mosaic virus (CSMV) were cloned into the pUC18-based vector, pG1 producing transcriptional fusions with the beta-glucuronidase (GUS) gene and nopaline synthase terminator sequence. The relative activity of each promoter construct was analyzed by a GUS expression assay of extracts from Zea mays (maize) Black Mexican Sweet protoplasts coelectroporated with the GUS reporter constructs and constructs in which individual CSMV open reading frames (ORFs) were placed under control of a cauliflower mosaic virus 35 S promoter. Weak promoter activity was observed for the promoter of the C1 and C2 ORFs (C1-C2 gene) and for the promoter of the V1 ORF. The activity of these promoters was unaffected by coelectroporation with the CSMV ORF constructs. Moderate activity was observed for the promoter of the V2 ORF (coat protein gene) which was enhanced by coelectroporation of the C1-C2 ORF construct. Sequences within the C1 C2 gene responsible for transactivation of the V2 ORF promoter were mapped close to the A site of a conserved NTP-binding sequence pattern within the C2 ORF. To a lesser extent activity for the promoter of the V2 ORF was enhanced by the V2 ORF construct providing evidence for positive autoregulation of the CSMV coat protein gene. PMID- 8438585 TI - Canine distemper virus L gene: sequence and comparison with related viruses. AB - We cloned the genomic RNA of canine distemper virus (CDV) and determined the nucleotide sequence of the large (L) protein-coding gene. The L gene is 6573 nucleotides long and contains a single open reading frame coding for a polypeptide of 2161 amino acids (MW 246,354). The precise 5' end of the viral genome consists of a 38-nucleotide leader region. The CDV L protein shows over 77% amino acid similarity with its morbilliform relative measles virus (MV) with nearly 67% of their amino acids conserved. The sequence homology of 11 negative strand viruses L proteins is compared and relatedness was found in the following decreasing order: CDV, MV, Sendai virus, parainfluenza virus type 3, simian virus 5, parainfluenza virus type 2, mumps virus, Newcastle disease virus, respiratory syncytial virus, vesicular stomatitis virus, rabies virus. The consensus sequence of proposed functional domains involved in L gene catalytic activities was well conserved in the CDV L protein. PMID- 8438586 TI - Genetic reassortment between avian and human influenza A viruses in Italian pigs. AB - Pandemic strains of influenza A virus arise by genetic reassortment between avian and human viruses. To examine the possibility that pigs serve as "mixing vessels" for such reassortment events (Scholtissek et al., Virology 147, 287-294, 1985), we phylogenetically analyzed the internal protein genes of classic H1N1, avian like H1N1, and human-like H3N2 viruses circulating among Italian pigs. The results show that human-like H3N2 strains isolated from 1985 to 1989 contained the internal protein genes of avian-like H1N1 viruses, whereas those isolated in 1977 and 1983 did not. Thus, at some time between 1983 and 1985, genetic reassortment took place between avian- and human-like viruses in Italian pigs. This study provides the first evidence supporting genetic reassortment between human and avian viruses in a natural swine environment. PMID- 8438587 TI - Selective alteration of the turnover of interferon beta mRNA in peritoneal macrophages from LPS-hyporesponsive mice and its role in the defective expression of spontaneous interferon. AB - Basal levels of interferon (IFN)-beta mRNA transcription were detected in both freshly explanted LPS-responsive (Lpsn) and LPS-hyporesponsive (Lpsd) peritoneal macrophages (PM). In vitro cultivation of PM resulted in a time-dependent reduction in the level of IFN-beta mRNA, which was far more rapid in Lpsd than in Lpsn PM. Treatment of Lpsn PM with cycloheximide (CHX) resulted in a marked accumulation of IFN-beta mRNA, which was not associated with an increase in IFN beta gene transcription. However, treatment of Lpsd PM with CHX did not induce accumulation of IFN-beta mRNA. CHX induced the accumulation of IFN-alpha-4 mRNA in both Lpsn and Lpsd PM, CHX enhanced the accumulation of two cytoplasmic factors interacting with AU-rich sequences within the 3' untranslated region of IFN-beta mRNA. We conclude that Lpsd PM exhibit an impaired capacity to stabilize IFN-beta mRNA that may account for their low expression of IFN-beta. PMID- 8438588 TI - Secretion of a truncated form of the human immunodeficiency virus type 1 envelope glycoprotein. AB - We have characterized a truncated secreted form of the HIV-1 envelope glycoprotein gene. Expression via a recombinant vaccinia virus resulted in a glycoprotein product of approximately 140 kDa (gp160t) and a minor cleavage product of 120 kDa (gp120). Pulse-chase analysis revealed that the majority of gp160t remained cell-associated and underwent degradation within 10-20 hr of synthesis. A secreted form (gp160t/sec) and gp120 were detected in the media 2-4 hr postsynthesis and were not significantly degraded within a period of 20 hr. Most of the cell-associated gp160t remained sensitive to digestion with endoglycosidase H, whereas gp160t/sec and gp120 were largely resistant. Gp160t, gp160t/sec, and gp120 formed oligomers which were stabilized by intermolecular disulfide bonds and/or noncovalent interactions and were also found to bind to soluble CD4. Both wild type gp160 and wild type gp160t were observed to undergo a post-translational modification 4-5 hr postsynthesis, resulting in glycoproteins with a slightly increased electrophoretic mobility. These differences in electrophoretic mobility remained following treatment with N-glycosidase F, indicating that they are not a consequence of N-linked oligosaccharide processing, but may represent an additional modification of the envelope glycoprotein. PMID- 8438589 TI - Sequence analysis of the nucleocapsid protein gene of rat coronavirus SDAV-681. AB - The nucleotide sequence of the 3'-end of the genomic RNA of sialodacryoadenitis virus strain 681 (SDAV-681) was determined. A large open reading frame encoding a 454-amino-acid protein was identified as the nucleocapsid protein (N) gene, since the predicted protein is similar in size, chemical properties, and amino acid sequence to the N proteins of other coronaviruses. The amino acid variance of the N proteins between SDAV and mouse hepatitis virus (MHV) is not markedly different from that among MHV strains. A high degree of genetic relatedness between SDAV and MHV was revealed in the intergenic and 3'-noncoding sequences as well as in the N gene. PMID- 8438590 TI - HIV infection of the BS-1 human stroma cell line: effect on murine hematopoiesis. AB - BS-1, a stroma cell line derived from normal human bone marrow, can support the growth of murine erythroid (BFU-E), granulocyte-macrophage (CFU-GM), and megakaryocyte (CFU-Meg) progenitor cells in a short-term in vitro coculture system. Exposure of BS-1 cell to the human immunodeficiency virus (HIV) prior to coculture results in a marked reduction in the stroma cell's ability to support murine BFU-E and CFU-GM. The effect of HIV on the BS-1 cell's hematopoietic support function (HSF) is dependent on the multiplicity of infection (m.o.i.). BS 1 stimulation of CFU-GM is significantly impaired at m.o.i. values ranging from 10 to 0.1, whereas its support of BFU-E colony formation is inhibited at m.o.i. values of 10 and 1. No effect of HIV on the BS-1 cell's HSF is observed with further log dilutions of virus. The HIV-mediated suppression of the BS-1 cell's ability to support hematopoiesis is neutralized by a monoclonal antibody (titers ranging from 1:10 to 1:50) to the Gp160 surface antigen of the virus. Suppression of BS-1 cell's HSF is again observed with log dilution (> 1:100) of the antibody. HIV suppression of the BS-1 cell's HSF correlates with replication of the virus. P24 antigen levels of 150 pG/ml are measured as early as Day 6 postinfection and rise to 360 pG/ml by Day 16 of culture. The results suggest that HIV may impair normal hematopoiesis by infecting the stroma cells of the bone marrow microenvironment and compromising their role as accessory cells in supporting the proliferation and differentiation of hematopoietic progenitor cells. PMID- 8438591 TI - Autologous neutralizing antibodies prevail in HIV-2 but not in HIV-1 infection. AB - Human immunodeficiency virus type 2 (HIV-2) has been reported to be less pathogenic than HIV-1. We have investigated the capacity of sera from nine HIV-2 infected individuals to neutralize their own autologous virus. All nine HIV-2 infected individuals neutralized autologous virus with titers ranging between 20 and 320. In contrast, we have previously reported that most HIV-1-infected individuals lack such antibodies. The difference between HIV-1 and HIV-2 infection was statistically significant (P < 0.0002, Pearson test) and the difference in neutralizing antibody prevalence may explain the faster disease progression in HIV-1-infected individuals than in HIV-2-infected individuals. PMID- 8438592 TI - African swine fever virus encodes a DNA ligase. AB - Sequencing of the EcoRI N' fragment of African swine fever virus (ASFV) DNA revealed an open reading frame encoding a protein similar to ATP-dependent DNA ligases. When the gene encoding this protein was expressed in Escherichia coli, a protein of the expected molecular mass was labeled in bacterial extracts upon incubation with [alpha-32P]ATP. The recombinant protein comigrated in SDS-PAGE with the putative viral DNA ligase detected in extracts of infected cells. We demonstrate that the recombinant protein is a DNA ligase by dissociation of the protein-[32P]AMP adduct with pyrophosphate and nicked DNA. The putatively adenylylated lysine in ASFV is surrounded by two arginine residues, instead of by two hydrophobic amino acids as in the other ATP-dependent DNA ligases. This might explain the high concentration of pyrophosphate necessary to revert the DNA ligase--AMP adduct in ASFV, 10- to 100-fold higher than that required for other DNA ligases. A comparison of the amino acid sequences reported for ATP-dependent DNA ligases disclosed three new amino acid motifs around the adenylylation site of these enzymes. ASFV DNA ligase has little similarity to the other enzymes at the ends of the molecule, but conserves the amino acid motifs of the central region. PMID- 8438594 TI - [Implantation of defibrillators with transvenous-subcutaneous electrode systems]. AB - In 23 patients an integrated pacemaker-defibrillator-system with transvenous subcutaneous lead system was implanted. Two transvenous electrodes were positioned, one in the right ventricle for sensing, pacing and defibrillation and one in the superior vena cava for defibrillation alone. Another electrode was positioned subcutaneously near the ventricular apex for defibrillation. In 22 patients (96%) the lead system could be implanted without a major complication. The defibrillation threshold for ventricular fibrillation was 16 +/- 5 joules. During follow up of 6 +/- 4 months all spontaneous tachyarrhythmias were successfully terminated. There were three complications during follow up. In 2 patients the transvenous electrode dislocated and one patient showed a sensing malfunction. In conclusion the non-thoracotomy approach is effective, reduces the perioperative risk and represents therefore a great advantage compared to peri /epicardial lead system. PMID- 8438593 TI - Canine distemper terminal and intergenic non-protein coding nucleotide sequences: completion of the entire CDV genome sequence. AB - Sequences critical for the transcription and replication functions of canine distemper virus (CDV) RNA polymerase were analyzed. The sequence was obtained from polymerase chain reaction (PCR) products using either c-DNA clones from a genomic library as template or in most instances genomic CDV RNA. Clones coding for the precise 3'- and 5'-ends of the CDV genome were sequenced and the results confirmed by additional PCR experiments. The virtual identity of terminal sequences and spacing at the two noncoding ends speak to the importance of these areas in replication and transcription. The sequence for each of the CDV gene boundaries was defined and all were compared to related viruses. This report completes the sequence determination of the CDV genome. PMID- 8438595 TI - [Importance of coronary dilatation in patients after bypass operation]. AB - 342 consecutive patients with recurrent angina pectoris were investigated 4.9 +/- 2.9 years after bypass surgery. According to the respective coronary morphology, angioplasty (PTCA) was performed in 110 patients (32%), repeat surgery in 32 (9%) and 200 patients (58%) were treated medically. Angioplasty was undertaken in 113 native coronary arteries (18 via a patent venous graft) and 29 bypass grafts. One vessel was dilated in 84 patients (76%) and more than one vessel in 26 patients (24%), giving an average of 1.3 vessels per patient. The initial success rate was 84% (120 of 142 vessels). The success rate varied from 60% in the midportion of venous grafts to 100% in the bypass protected left main stem. One patient died from complications (0.9%) and 5 patients (4.5%) suffered a myocardial infarction. Revascularisation was complete in 64 patients (58%) and remained incomplete in 40 patients. Clinical state improved in all but 7 patients and 70 patients (64%) became symptom-free. After 6 months 88 patients were clinically reevaluated. 52 patients (59%) still showed improvement in anginal status or remained symptom free. Due to recurrent symptoms a re-angioplasty was performed on 21 patients and 6 patients had to be reoperated. In conclusion, coronary angioplasty is frequently a feasible alternative to reoperation with calculable risks in patients with recurrence of symptoms after prior bypass surgery. PMID- 8438596 TI - Spirometric alterations in patients with reduced renal function. AB - Spirometric parameters were measured in 49 patients with reduced renal function. The patients were divided according to their glomerular filtration rate (GFR) into two groups: (A) GFR < 0.2 ml s-1-end stage renal failure; (B) GFR > or = 0.2 ml s-1. FEV1 and FEF25-75 were significantly lower in the end-stage renal failure group of patients. 80% of the patients with GFR < 0.2 ml s-1 and 31% of the patients with GFR > or = 0.2 ml s-1 had spirometric evidence of small airways dysfunction. In multiple stepwise regression analysis with ventilatory parameters as dependent variables and renal function, total protein, urea, creatinine, sodium, and hemoglobin levels, proteinuria, diuresis, and history of left ventricular failure as independent variables only GFR and total protein correlated significantly with FEV1 and FEF25. In conclusion, our study demonstrates that impairment of spirometric function in patients with renal insufficiency is continual, with reduction of GFR, and thus small airways dysfunction may be expected not only in patients with end-stage renal failure, but also in those with moderate GFR reduction. PMID- 8438597 TI - Blood biochemical changes in trained subjects during prolonged restriction of physical activity and chronic hyperhydration. AB - The objective of this investigation was to determine the effect of daily fluid and salt supplementation on biochemical changes in the serum of endurance trained athletes after exposure to hypokinesia (decreased number of steps from 15,000 to 1000 steps/day). The studies were performed after exposure to 364 days of hypokinesia on 18 long-distance runners aged 19-24 years who had a V02 max of 67.5 ml/kg/min. The volunteers were divided into three equal groups: The 1st group underwent a normal ambulatory life (control subjects), the 2nd group was placed under continuous restriction of motor activity, and the 3rd group was kept under continuous restriction of motor activity whilst consuming daily supplements of 26 ml water/kg body weight and 0.16 g sodium chloride/kg body weight. For hypokinesia the number of steps taken per day by the volunteers in groups 2 and 3 were restricted to an average of 1000. During the hypokinetic period of 364 days and posthypokinetic period of 30 days urea, glucose, acid-soluble phosphorus, inorganic phosphorus, cholesterol (low-density and high-density lipoprotein) and phospholipids were measured at predetermined intervals. During the hypokinetic period in hyperhydrated volunteers urea, cholesterol, phospholipids, inorganic phosphorus and acid soluble phosphorus decreased, while glucose increased. In hypokinetic volunteers a significant increase in urea, cholesterol, phospholipids, inorganic phosphorus and acid soluble phosphorus, and a significant decrease in glucose was demonstrated. During the posthypokinetic period these biochemical changes normalized in both hypokinetic and hyperhydrated volunteers. It is concluded that daily fluid and salt supplementation may effectively counteract changes in blood biochemistry in endurance trained subjects during prolonged restriction of physical activity. PMID- 8438598 TI - Coffee, lipoproteins and cardiovascular disease. AB - Morbidity and mortality of cardiovascular diseases are related to life-style (in particular diet, exercise and smoking). Many epidemiological studies have demonstrated that nutrition significantly affects cholesterol (C) and lipoprotein levels i.e. LDL-c and HDL-c, whereby an increase in LDL-c and a decrease in HDL-c represent independent primary risk factors for atherogenesis. For many years studies have been performed to discover other risk factors, one of the most important being the influence of coffee consumption. Epidemiological analysis of a single dietary factor produces many methodological difficulties, which may explain the inconsistent study findings regarding the effects of coffee. Thus, these studies have to be performed with large numbers of participants over many years, during which time dietary and drinking habits have to be stabilized in order to detect possible associations. Coffee contains a number of biochemically active substances, one of the most important being caffeine, a xanthine derivative. Recent studies have concentrated on the methods of preparation of coffee, which vary from country to country. A lipid fraction of boiled coffee, which is widely consumed in Northern European countries has been shown to significantly raise C and LDL-c in a dose-dependent manner. Filtered coffee, however, does not contain this lipid elevating fraction. Thus, recommendations concerning the consumption of coffee have to take into account the particular method of preparation, the amount consumed and predisposing risk factors that could interact with coffee consumption such as hypertension, hyperlipidaemia, cardiac arrhythmia. PMID- 8438599 TI - Prostacyclin and molsidomine synergise in their fibrinolytic and anti-platelet actions in patients with peripheral arterial disease. AB - In vitro prostacyclin (PGI2) and nitric oxide (NO) synergise in their anti aggregatory actions on blood platelets. Presently, we have studied an interaction of molsidomine (ML--pro-drug for the NO-donor SIN-1) and PGI2 in 20 patients with peripheral arterial disease (PAD) on the plasma fibrinolytic system and platelet aggregability. A synergism of these drugs in their fibrinolytic action as measured by shortening of euglobulin clot lysis time (ECLT) and in their anti platelet action as measured by an increase in the ratio of free platelets to platelet aggregates was observed. It seems that PGI2 and ML activated the fibrinolytic system by two independent mechanisms i.e. by a PGI2-induced direct release of pro-fibrinolytic t-PA from endothelial cells and by a ML-induced suppression of the release of anti-fibrinolytic PAI-1 from platelets. This may constitute a basis for the synergism. A synergism between PGI2 and ML in their anti-platelet action seems to be rooted in the potentiation by cyclic-GMP on the anti-aggregatory action of cyclic-AMP in platelets. On the other hand, no synergism between PGI2 and ML was observed in their hypotensive effects as measured by systolic and diastolic arterial blood pressure. It may well be that the synergism in fibrinolytic and anti-platelet actions between stimulators of adenylate and guanylate cyclases accompanied by a lack of synergism in their hypotensive actions may allow reduction of the therapeutic doses of either stimulator, thus avoiding hazards of their hypotensive side effects. PMID- 8438600 TI - [10 years Helicobacter (Campylobacter) pylori]. PMID- 8438601 TI - [Glycogenoses and other metabolic hepatopathies in childhood and adolescence]. PMID- 8438602 TI - [Frequent diagnostic errors in fever]. PMID- 8438603 TI - [Exposure to toxic heavy metals--their sequelae for immune competence in the human]. PMID- 8438604 TI - [Therapy of erectile dysfunction with corpus cavernosum autoinjection and current legal aspects]. PMID- 8438605 TI - [A case from general practice (60): epigastric pain with jaundice]. PMID- 8438606 TI - [From clinicum medicum universitatis to Clinic of Internal Medicine of the Berlin Charite--stages in its development]. PMID- 8438607 TI - [Alfons Krautwald]. PMID- 8438608 TI - Epidemiology of diarrhoeal disease: implications for control by vaccines. AB - Vaccines present perhaps the most attractive solution to the worldwide problem of diarrhoeal disease. Epidemiological evidence has important implications for the development and use of such vaccines, and results of studies on diarrhoeal diseases in developing and developed countries, in particular among children, and travellers' diarrhoea are reviewed. The virulence and pathogenicity of various enteropathogens are discussed, and the extent to which immunity may be acquired. It is concluded that the development of appropriate vaccines may be a complex task. PMID- 8438609 TI - Novel vaccination strategies for the control of mucosal infection. AB - Enteric disease remains one of the greatest causes of mortality and morbidity in both human and veterinary species. There has been a remarkable lack of success in vaccination to control mucosal disease and it is therefore apparent that novel strategies are required to achieve effective mucosal immunity. Basic studies described in this paper have addressed problems associated with antigen handling and the induction of an immune response in the intestine, and the subsequent dissemination of effector cells and molecules to intestinal and extra-intestinal submucosal regions. Effective induction of IgA responses is dependent on T-cell help and requires cognate interactions between T cells and B cells within organized gut-associated lymphoid tissue (GALT). The delivery of an IgA antibody response to mucosal sites is also a T cell dependent but antigen driven process. The normal route by which antigen is taken up by GALT is via the epithelial surface but antigen presented in this way via villus epithelial cells generates predominantly a suppressor response. Strategies designed to overcome this effect include the use of powerful adjuvants (such as cholera toxin, muramyldipeptide and phorbol esters), the use of immunogenic carriers, or delivery via liposomes, microspheres or genetically engineered viral or bacterial vectors. Alternatively, the feasibility of accessing GALT via the serosal surface by administration of intraperitoneal antigen in oil emulsion has been explored and a vaccine formulation (Auspharm (patent pending)) has been developed which is suitable for IP delivery in commercial applications. PMID- 8438610 TI - Circulating cellular immune response to oral immunization of humans with cholera toxin B-subunit. AB - Peripheral blood mononuclear cells were taken from subjects before and after oral immunization with cholera toxin B-subunit. Cells obtained from naive volunteers before immunization did not proliferate in vitro to B-subunit. Oral immunization induced a proliferative response in all volunteers with a peak stimulation index of 20, and was detected up to 1 year later. The proliferative response kinetics suggest the appearance in the blood of primed T cells from the gut coinciding with the disappearance of primed plasmablasts from the circulation, supporting the concept of a common mucosal immune system in man for T and B cells. PMID- 8438611 TI - The PhoP virulence regulon and live oral Salmonella vaccines. AB - The PhoP virulence regulon is essential to Salmonella typhimurium mouse typhoid fever pathogenesis and survival within macrophages. This virulence regulon is composed of the PhoP (transcriptional regulator) and PhoQ (environmental sensor) proteins and the genetic loci they positively (pags for PhoP activated genes) and negatively (prgs for PhoP repressed genes) regulate. Three regulated loci pagC, pagD, and prgH, when singly mutated, affect the virulence of S. typhimurium for mice. Strains with phoP locus mutations are effective as live vaccines in mice, and strains with a constitutive regulatory mutation, a point mutation in PhoQ, can protect mice against typhoid fever when only very few organisms are administered. The addition of various PhoP regulon mutations further attenuates aroA mutants of S. typhimurium, suggesting that these mutations would be useful in further attenuating vaccine strains with metabolic pathway mutations. The phoP, phoQ, pagC, and pagD genes are highly conserved between S. typhimurium and S. typhi and may be valuable as mutations in live vaccines for human typhoid fever. A plasmid suicide vector that allows deletion of the pagC gene and stable insertion of heterologous antigen genes within the deleted pagC locus has been constructed and used successfully in S. typhimurium and S. typhi. PMID- 8438612 TI - Effect of parenteral immunization on the intestinal immune response to Salmonella typhi Ty21a as measured using peripheral blood lymphocytes. AB - The effects of parenteral administration of a killed typhoid vaccine on the intestinal immune response to live orally administered Salmonella typhi Ty21a in human subjects was assessed using an assay of in vitro specific antibody production by circulating peripheral blood lymphocytes (PBL). Previous priming with the parenterally administered vaccine had no effect on secondary immune responses to a live oral vaccine in humans with this response not differing in magnitude or duration from that following the primary oral vaccination course (p = 0.38). Following the primary PBL anti-LPS IgA response to an oral course of live vaccine in all subjects (6/6), boosting with a single oral dose of live vaccine resulted in 0/6 responders, while 2/11 subjects responded after a single dose of parenteral vaccine. No additional responses were evident after the second parenterally administered booster dose. PBL IgG and IgM responses were also demonstrated following oral vaccination, with 1/6 and 2/6 subjects parenterally vaccinated demonstrating IgM PBL responses after the first and second vaccination respectively. This study confirmed that parenteral vaccination did not impair the PBL IgA immune response to a secondary course of live orally administered organisms, and that multiple parenteral booster doses did not induce primary or secondary recirculation of antigen-specific PBL. PMID- 8438613 TI - Biodegradable microparticles for oral immunization. AB - Ovalbumin (OVA) was entrapped in poly(lactide-co-glycolide) microparticles and administered to mice. Following intraperitoneal immunization, the microparticles induced both proliferative T-cell responses and cytotoxic T-cell responses in spleen cells. Following oral immunization, the mean salivary IgA antibody response to microparticles was significantly greater than the response to soluble OVA (p < 0.0001). Serum IgG antibody levels were also significantly greater in the group administered microparticles (p < 0.001). Cholera toxin B subunit was also entrapped in microparticles. Following oral immunization in mice, specific antibody-secreting cells were detected both in the spleens and in the mesenteric lymph nodes. PMID- 8438614 TI - Preclinical evaluation of microencapsulated CFA/II oral vaccine against enterotoxigenic E. coli. AB - Colonization Factor Antigen (CFA/II) from enterotoxigenic Escherichia coli (ETEC) prepared under good manufacturing practices (GMP) was successfully incorporated into biodegradable poly(D,L-lactide-co-glycolide) (PLGA) polymer microspheres (BPM) under GMP and found to be safe and immunogenic when administered intraduodenally to rabbits. Following vaccination, Peyer's patch cells responded by lymphocyte proliferation to in vitro challenge with CFA/II. Also, B cells secreting specific anti-CFA/II antibodies were found in spleens following vaccination. No pathological changes were found following total necropsies of ten rabbits vaccinated with CFA/II BPM. Sixty-three per cent of the CFA/II BPM were between 5 and 10 microns diameter by volume particle size distribution; 1.17% protein content; 2.15% moisture; < 0.01% acetonitrile; 1.6% heptane; 22 non pathogenic bacteria and three fungi per 1 mg protein dose; and passed the general safety test. We conclude that the CFA/II BPM oral vaccine is immunogenic and safe to begin a Phase I clinical safety study following Investigational New Drug approval. PMID- 8438615 TI - Strategies for development of potential candidate Shigella vaccines. AB - Bacillary dysentery, caused by Shigella bacteria, is a major enteric disease responsible for over 200 million infections annually with 650,000 fatal cases. Due to its high communicability, improvement of hygienic standards alone should reduce the spread of dysentery. However, such measures are expensive, and in the communities (e.g. penitentiaries and asylums) or in the areas of the world where bacillary dysentery is most frequently encountered (e.g. in the developing countries) they are not likely to take effect in the reasonably near future. Therefore the possibility of other preventive means such as anti-dysentery vaccines have been explored over the past 40 years. Recently, increased understanding of the molecular biology of bacillary dysentery and the possibility of designing well characterized vaccine strains have increased interest in the field. Several promising vaccine candidates are at various levels of investigations, but to date no Shigella vaccines are available for public health purposes. In this review, beyond the relevant basic information about the pathology, pathomechanism and molecular biology of bacillary dysentery, the various approaches and strategies to construct a safe and immunogenic anti dysentery vaccine are critically discussed. PMID- 8438616 TI - Safety and immunogenicity of the live oral auxotrophic Shigella flexneri SFL124 in adult Vietnamese volunteers. AB - The live, auxotrophic dependent Shigella flexneri Y vaccine strain SFL124 with a deleted aroD gene was tested in 30 healthy adult male Vietnamese volunteers. A single dose of 2 x 10(9) live bacteria was given orally to 15 volunteers, whereas 15 received three doses every other day. None of the volunteers reacted with fever or diarrhoea and SFL124 was excreted by all for a mean of 2.8 (single dose) and 2.6 (three doses) days. A total of 27 of 30 (90%) and 26 of 30 (87%) responded with significantly (0.001 < p < 0.01) increased antibody-secreting cell (ASC) numbers against Shigella flexneri Y lipopolysaccharide (LPS) and invasion plasmid-coded antigens (Ipa). A faecal IgA antibody response to LPS and Ipa was seen in 20 of the 30 (67%) volunteers against both antigens. Serum antibody responses were seen in 23 of 30 (77%) against the LPS and in 17 of the 30 against Ipa. The three-dose schedule elicited only somewhat stronger immune responses than the single-dose schedule. A booster dose of 2 x 10(9) live bacteria was given to half of the volunteers in each group after 6 months, the other half received the same dose after 12 months. Following the booster at 6 or 12 months (i) the excretion of SFL124 was significantly shorter (p < 0.05) than after primary vaccination; (ii) the anti-S. flexneri LPS and anti-Ipa faecal sIgA titres were significantly higher (p < 0.05 to p < 0.01) than after primary vaccination; (iii) the anti-LPS and anti-Ipa ASC responses were significantly lower (p < 0.05) and of shorter duration than after primary vaccination, and (iv) the serum anti-LPS and anti-Ipa responses were significantly elevated (p < 0.05) and similar to those seen after primary vaccination. The results indicate that SFL124 is a safe, live vaccine strain with a negligible reactogenicity in adults living in a Shigella endemic area. SFL124 induces specific immune responses against LPS and Ipa with a mucosal memory lasting for at least 1 year. PMID- 8438617 TI - Evaluation of Shigella vaccine safety and efficacy in an intranasally challenged mouse model. AB - Five Shigella vaccine candidates (EcSf2a-1, EcSf2a-2, Sfl124, T32-Istrati and SMD) were tested for safety and efficacy in Balb/cJ mice using an intranasal challenge model. Experiments in this model suggest that (i) the relative attenuation of vaccines can be determined in mice by intranasal inoculation, (ii) all vaccines tested elicited antibacterial mucosal immunity protecting against pulmonary infection with Shigella flexneri 2a, (iii) protection was associated with serum IgA and/or IgG antibody recognizing the 2a somatic antigen. PMID- 8438618 TI - Shigella flexneri 2a and sonnei I vaccine with two attenuating markers: construction, tolerability and immunogenicity in 143 children aged 3-17 years. AB - The vaccine candidates were constructed through stepwise incorporation of weakly attenuated purine auxotrophy with subsequent rifampicin resistance (RNA polymerase) mutation to yield optimal attenuation. These strains showed a maintained invasiveness for conjunctival epithelia. Therefore, while not causing keratoconjunctivitis, they were excreted for a short but marked period and provided partial protection in the Sereny test. Children tolerated the maximum dose of 1-3 x 10(9) colony-forming units (c.f.u.) of lyophilized vaccine without side effects. This total dose distributed among three oral inoculations, induced coproantibodies in 70% of recipients during the first three months. However, the single application of this total dose for primary immunization or booster proved to be more efficient: 90% of the subjects had markedly elevated titres for not less than six months. PMID- 8438619 TI - Live oral vaccines against cholera: an update. AB - One hundred years elapsed between the first (live, parenteral) cholera vaccine that entered clinical trials in 1885 and the field trials of two oral inactivated cholera vaccines undertaken in Bangladesh in the mid-1980s. The oral inactivated vaccines advanced the art by establishing, convincingly, that oral vaccines could protect (although multiple doses were required) and that (at least in adults) protection could last 3 years. Attenuated Vibrio cholerae O1 strain CVD 103-HgR (deleted of the cholera toxin A subunit gene and harbouring a gene encoding resistance to Hg++) constitutes another significant advance. This live oral vaccine is well tolerated and highly immunogenic in adults and children and highly protective (in adult volunteer challenge studies) following ingestion of of a single dose. PMID- 8438620 TI - Recombinant enterotoxins as vaccines against Escherichia coli-mediated diarrhoea. AB - A fusion protein, comprising the B subunit of the heat-labile enterotoxin and a portion of the precursor to the heat-stable enterotoxin of Escherichia coli, has been created by recombinant genetic techniques. It is exported successfully to the bacterial periplasm and assembles into pentamers which retain the ability to bind to GM1 ganglioside. Native toxin epitopes are displayed and the molecule can be easily purified from periplasmic extracts of cells expressing the gene fusion. Although the protein carries the natural sequence of the heat-stable enterotoxin, it is greatly attenuated in toxicity. Systemic immunization of mice or oral administration of the fusion elicits antibody responses against both classes of E. coli enterotoxin. PMID- 8438621 TI - Antigenicity, immunogenicity and vaccine efficacy of the galactose-specific adherence protein of Entamoeba histolytica. AB - Entamoeba histolytica is an enteric protozoan that causes amoebic colitis and liver abscess. Human immunity to E. histolytica is apparently mediated by a serum antibody response and amoebicidal cellular mechanisms. The galactose-specific adherence protein of E. histolytica is a 260 kDa glycoprotein which mediates amoebic in vitro adherence to human colonic mucins, epithelium, and inflammatory cells. Amoebic lysis of cells is dependent upon binding by this adherence protein. Serum IgG and salivary IgA antibodies from greater than 90% of subjects with invasive amoebiasis recognize the adherence protein's 170 kDa heavy subunit. Incubation of peripheral blood mononuclear cells from antibody-positive subjects with the purified galactose-specific adherence protein induces in vitro T lymphocyte proliferation, IL-2 and gamma interferon production, and direct lymphocyte amoebicidal activity. The rationale for an adherence protein vaccine includes sIgA blockage of amoebic binding to colonic mucins, humoral IgG prevention of parasitic adherence in tissues, and development of amoebicidal cell mediated immunity. Immunization of gerbils with purified adherence protein in Freund's adjuvant provides protection against intrahepatic challenge with the trophozoites. In summary, the galactose specific adherence protein of E. histolytica contains highly conserved B- and T-cell epitopes, and has a high degree of vaccine efficacy in the gerbil model of amoebic liver abscess. PMID- 8438622 TI - The conference on vaccines protective against enteric diseases. PMID- 8438623 TI - K and Ca content of fresh green tea, black tea, and tea residue determined by X ray fluorescence analysis. AB - X-Ray fluorescence (XRF) can be successfully used for the qualitative and quantitative elemental analysis of various agricultural products. Its simplicity, high throughput and the possibility of automation make it useful for screening large numbers of samples. The K and Ca content of 138 samples of fresh green tea, black tea and black tea residues were determined by applying the XRF system. Such a method of mineral analysis of food products is not very common. Tea from different tea-growing areas of Turkey, green tea of different shooting periods, black tea processed at different tea plants and tea residues from these black tea were analysed. The K content of green tea, processed black tea and tea residues after brewing were found to have ranges of 19,049-26,254 mg/kg, 21,904-26,883 mg/kg and 9,468-13,778 mg/kg, respectively. In the same samples the Ca content was determined as 3,580-4,799 mg/kg, 3,370-4,823 mg/kg, and 3,743-5,733 mg/kg, respectively. These findings were compared with the results of atomic emission techniques and it was concluded that the XRF system could be effectively used for quantitative analysis of the K and Ca content of tea samples. PMID- 8438624 TI - Determination of optimum pH and temperature for pasteurization of citrus juices by response surface methodology. AB - Optimization of microbial death, enzyme inactivation and vitamin C retention during pasteurization of pH-adjusted orange juice is discussed free of equipment dependent parameters such as the heating lag. The pH-temperature optimum was determined by response surface methodology in the range of 65 degrees C-75 degrees C and pH 2.5-4.0. The results implied that there was no pectinesterase activity below pH 3.5. Leuconostoc mesenteroides had its maximum and minimum thermal resistance at pH 3.5 and pH 2.7, respectively. For an ideal theoretical process requiring four log cycles of microbial reduction the optimum pasteurization conditions were 12 min at 75 degrees C and pH 2.7. PMID- 8438625 TI - [Pre-conception counseling and pregnancy in chronic inflammatory bowel diseases- Crohn disease and ulcerative colitis]. AB - Since chronic inflammatory diseases start to develop during the fertile years, the possibility of a mutual influence of pregnancy and bowel disease obviously must be considered. The knowledge about the interference between disease and pregnancy influences the management of pregnancy and delivery as well as of the disease itself. Intensive care, including genetic counseling, dietary management, and drug therapy ought to start even before pregnancy. In the care of the pregnant patient with Crohn's disease or ulcerative colitis corticosteroids and sulphasalazine may be used just as in the nonpregnant patient. An increased activity of the disease in the beginning of pregnancy causes high rates of prematurity, spontaneous abortions, and stillbirths. Frequency of defects in embryonic development varies between 0 and 4% and is even higher in severe cases of Crohn's disease. Prophylactic drug administration in pregnancy is not suitable to decrease the risk of exacerbation. Several studies revealed that the risk of exacerbation is not increased during pregnancy. Low activity in the onset of pregnancy is continued in 61%. Higher rates of abdominal and vaginal operative deliveries (26% in Crohn's disease) seems to be associated with active intervention on the base of activity indices. PMID- 8438626 TI - [Disorders of thyroid function and sterility in the woman]. AB - In 118 successive infertile women (aged 22-40 years, median 30 years) with longstanding infertility from our infertility clinic we performed an endocrinological (TRH-test, TT3, TT4, TBG, antibodies) as well as a morphological thyroid examination (sonography and 99mTc-scintigraphy. The same endocrinological investigations except TRH-test and a thyroid sonography was performed in the control group (50 fertile women, aged 24-39 years, median 33 years). Two patients were hyperthyroid and one patient had primary hypothyroidism. Antibodies against thyroglobulin (TgAK) and thyroid peroxidase (TPO) or microsomal antibodies (MAK) were found in 19 patients (19%). The incidence of biochemical immunological thyroiditis was not significantly different from the control group. But thyroid volume was significantly higher in patients (21 versus 15.6 ml, p < 0.03). Goitre (> 18 ml) was diagnosed in 52% (n = 57) of the patients, although 43 had normal TRH-test results with delta TSH 2.5-12.5 microU/ml. So-called subclinical (latent) hypothyroidism (delta TSH > 12.5 microU/ml) was found in 29 patients; 18 of these infertile women had no goitre. Iodine avidity (99mTc-uptake) increased significantly with the increase in thyroid volume, but showed a tendency to lower values with increasing delta TSH-values and higher iodine avidity in women with thyroid enlargement (n = 109). During follow-up of 12-24 months 10 women with goitre conceived spontaneously after initiation of iodine and/or L-thyroxine 100 micrograms treatment. These data support recent studies, that factors other than TSH cause thyroid enlargement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8438627 TI - Multiple pregnancies as a result of IVF and ET in a program without cryopreservation possibility. AB - Of the 71 clinical pregnancies achieved in the IVF and ET program at the Institute for the Care of Mother and Child between January 1989 and June 1992 22 were multiple (30.9%). In seven cases (31.3%) spontaneous reduction occurred. A total of six patients underwent a multi-fetal pregnancy reduction. Close monitoring of ovarian response, limitation of the number of transferred embryos, selection of the most viable embryos using cocultivation systems and embryo freezing should be used to avoid the higher order multiple pregnancies after IVF ET. PMID- 8438628 TI - [Comparison of Doppler ultrasound assessment of utero-placento-fetal perfusion in normal pregnancies and in those with threatened premature labor]. AB - The aim this study to compare perfusion parameters, measured by Doppler sonography, between normal pregnancies and pregnancies with symptoms of preterm labor. The patient collective comprised of 3 groups: 62 normal pregnancies (group 1), 23 preterm labor before tocolysis (group 2) and 114 preterm labor up to 48 hours under tocolysis (group 3). In each case pulsatility index was measured in the uterine artery on the placental side and non-placental side, umbilical artery, fetal descending aorta and middle cerebral artery. In the contrary to patients in group 1, patients in group 2 and 3 showed significantly elevated PI values in uterine artery placental side and non-placental side, respectively. The median of PI for both uterine arteries in both groups was significantly higher compared to that of group 1. However, 1/3 of patients with preterm labor showed pathologic uterine perfusion before or during tocolysis. The values of PI in umbilical artery, fetal descending aorta and middle cerebral artery did not reveal significant difference in all group. Nevertheless, 30% of pregnancies with preterm labor have pathological perfusion in the fetal descending aorta. We conclude that some patients with symptoms of preterm labor have pathological perfusion in uterine arteries and fetal descending aorta not induced by uterine contractions. We believe that the complex assessment of uterine perfusion should include the median PI value of both uterine arteries in order to have a reliable information. A short-term intravenous tocolysis with betamimetics does not seem to have a positive influence on the hemodynamic insufficiency. PMID- 8438629 TI - IgG, IgM and IgA umbilical blood concentrations in normal singleton vaginal deliveries with stinking amniotic fluid or intrapartal maternal febrility > or = 38 degrees C or duration of delivery > 12 hours. AB - Total of 321 preterm/term newborns delivered in normal singleton vaginal deliveries was studied. Babies were divided into two groups. The first one includes 62 newborns with single, isolated clinical sign: stinking amniotic fluid or intrapartal maternal febrility > or = 38 degrees C or duration of delivery > 12 hours. The second one (control group) contained 259 newborns with no such a sign. In both groups the umbilical cord blood IgG, IgM and IgA concentration (g/L) were quantified by a radial immunodiffusion method. The obtained values were classified into the groups according to 500-grams-birth-weight-ranges. The differences of the mean IgG, IgM and IgA concentrations between the each 500 grams-birth-weight-range subgroup separately in both control and experimental group so as between the same subgroup of the control and experimental group were tested by the means of the Student's t-test. Obtained results did not express the significant differences in the mean IgG, IgM and IgA umbilical cord blood concentrations between the experimental and control group of the newborns. PMID- 8438630 TI - Postprandial blood-glucose-screening for gestational diabetes. AB - The author reports on his 6-year experience (1. 1. 1985--31. 12. 1990) in screening for gestational diabetes at the Clinic of Gynecology and Obstetrics of the Medical University of Debrecen. The results of screening performed on a group of 1124 pregnant women with risk factors are evaluated. The diagnosis was established on the basis of postprandial glucose determinations and 75 g oral glucose challenge. The examinations revealed that gestational diabetes developed in 24% of patients with positive urinary glucose test, in 31% of patients with poor obstetrical history, and in 52% of those having family history of diabetes. The overall incidence of gestational diabetes was found to be 34% in the screened group of patients. At the time of the study the number of gravid women in Debrecen was 15.749. The prevalence of gestational diabetes was 1.95%. PMID- 8438631 TI - Studies on carbohydrate metabolism in physiological pregnancy. AB - Tests were performed on fasting (N = 780), postprandial (N = 890), and glucose loaded (50 and 75 g glucose given orally) blood samples in the period from 10 to 40 weeks of gestation. The highest physiological value of glucose was given as x + 2SD. Fasting blood glucose was found to be stable during pregnancy with the highest value of 5.65 mmol/l. Postprandial blood glucose concentrations showed a significant rise (p < 0.01), and the x + 2SD value remained below 7.5 mmol/l. The highest levels of blood glucose concentrations after 50 g one, two, and three hours following glucose loading were 8.43. 7.69 and 5.7 mmol/l, and after 75 g glucose loading: 9.73, 7.56 and 5.79 mmol/l respectively. PMID- 8438632 TI - [Mortality and fatalities after cesarean section in West Berlin 1975 to 1989]. AB - From 1975 till 1989 246 621 deliveries were registered in West-Berlin, 29,257 of which were caesarean sections. 41 cases of maternal death appeared. 19 women succumbed after vaginal delivery, 22 after caesarean section. Thus, during the 15 years of observation, mortality after caesarean section was 0.75% (1 case of maternal death on 1330 caesarean sections), whereas lethality--death due to surgical or anesthetical complications--was 0.41% (1:2438). At the end of the 80ies lethality of caesarean section was three-fold higher than of vaginal delivery. PMID- 8438633 TI - HDL and coronary artery disease. PMID- 8438634 TI - Recognition and management of panic disorder. PMID- 8438635 TI - Impotence: the internist's approach to diagnosis and treatment. PMID- 8438636 TI - Recognition and elimination of tuberculosis. PMID- 8438637 TI - T lymphocytes and cytokine networks in asthma: clinical and therapeutic implications. PMID- 8438638 TI - Erythropoietin therapy in renal failure. AB - It is indeed rare that a medication can do so much good and be associated with so few side effects and complications. The judicious use of Epo along with informed dosing practices will lead to an overwhelming favorable balance in the risk/benefit ratio of care. The move from a very specialized area of need into a more generic arena has done well for the development of drugs of this nature and may help stimulate further research in other "orphan" areas of drug need. PMID- 8438639 TI - Fulminant hepatic failure. PMID- 8438640 TI - The intestinal and liver complications of diabetes mellitus. AB - Gastroparesis, constipation, diarrhea, and fecal incontinence occur frequently in diabetics with long-standing and often poorly controlled insulin-dependent diabetes. These motor abnormalities of the gastrointestinal tract tend to be associated in these patients with evidence of autonomic neuropathy and other diabetes-related complications such as peripheral neuropathy, nephropathy, and retinopathy. The management of these derangements of motility is generally frustrating and very difficult. The prokinetic agents currently available have fewer side effects than previously used drugs, and have expanded the treatment options for diabetics with motility disorders of the gastrointestinal tract. The treatment of diabetic diarrhea remains aimed at the symptom because the cause is often unknown. The diagnosis of diabetic diarrhea depends on a careful and judicious assessment, which allows for the distinction of this condition from other causes of diarrhea. For example, celiac disease can occur in insulin dependent diabetics, but it is specifically treated by the elimination of gluten from the diet. In recent years, we have also gained a better understanding of the liver and biliary tree abnormalities that occur in the diabetic. The most common hepatobiliary lesions found in these patients include excessive glycogen deposition, fatty liver, and gallstones. Cirrhosis of the liver can develop in diabetics as a result of progressive fatty steatosis, pericentral hepatic fibrosis, and, at times, central hyaline sclerosis. Future study of the underlying pathogenesis of diabetes may one day allow us to find common threads in the seemingly disparate gastrointestinal and hepatic complications of this disease. PMID- 8438641 TI - The newer uses of growth hormone in adults. PMID- 8438642 TI - Osteoporosis: pharmacologic treatment strategies. PMID- 8438643 TI - Left ventricular mass, diastolic dysfunction, and hypertension. PMID- 8438644 TI - The endocrine complications of acquired immunodeficiency syndrome. PMID- 8438645 TI - Infection and autoimmunity. PMID- 8438646 TI - The use of esophageal function tests. AB - The esophagus is subject to a variety of disorders that can be mechanical or functional in origin. In addition, GERD is quite common and can present with atypical manifestations. Mirroring these disorders, the esophageal function tests can likewise be broken down into anatomic and functional studies. The barium esophagogram, when properly performed, is probably the single most important test because it evaluates both oropharyngeal and esophageal anatomy and motility as well as the presence or absence of GERD. Endoscopy allows direct inspection and sampling of the esophagus. Esophageal scintigraphy and manometry play less important but well defined roles. Finally, the advent of prolonged ambulatory esophageal pH monitoring has advanced our knowledge about GERD and has particularly helped in the diagnosis of patients with atypical reflux presentations such as chest pain and pulmonary or otolaryngologic symptoms. PMID- 8438647 TI - Bacterial overgrowth of the gastrointestinal tract. PMID- 8438648 TI - Polycystic kidney disease: hereditary and acquired. PMID- 8438649 TI - Implantable cardioverter-defibrillators. PMID- 8438650 TI - The benefits and risks of exercise training: the exercise prescription. AB - The physiologic responses to exercise are mediated by a complex interaction of central, peripheral, and neurohumoral stimuli designed to increase cardiopulmonary function. With repetitive exercise, significant cardiovascular and muscular adaptations occur that facilitate and enhance the response to exercise. Exercise is beneficial not only to younger healthy individuals, but to patients with many chronic medical conditions and to elderly individuals as well. Physical activity has a role in the reduction of major cardiac risk factors and in both the primary and secondary prevention of cardiac events. With proper evaluation and counseling, exercise can be performed safely, even among patients with cardiovascular and other chronic diseases. Given the high percentage of the U.S. population whose sedentary lifestyle predisposes them to the development of cardiovascular disease and the numerous beneficial effects of exercise, it is prudent to prescribe exercise as a means of improving individual and general public health. PMID- 8438651 TI - A clinician's primer on the circadian clock: its localization, function, and resetting. PMID- 8438652 TI - Disturbed fluid and electrolyte homoeostasis following dehydration in elderly people. AB - Disturbances in homoeostatic capacity are typical of the ageing process. Changes in the neuroendocrine controls of salt and water homoeostasis with age make elderly people more susceptible to fluid and electrolyte disturbances such as dehydration and overhydration. Not only do elderly subjects show reduced thirst and water intake following dehydration, but their kidneys are less able to retain water. This reduced thirst and water intake is not dependent on palatability of the liquids offered as the amounts drunk are no different if water alone or a variety of beverages are offered to healthy elderly dehydrated men. It is of interest that the arginine vasopressin (AVP) response to dehydration is maintained in elderly subjects, indicating that their reduced renal water retentive capacity is due to relative renal resistance to vasopressin. The mechanism underlying the reduced thirst is unclear. Dehydration causes plasma hypertonicity and reduced extracellular fluid (ECF) volume, both of which stimulate thirst and AVP secretion. Elderly subjects show deficits in sensing the reduced ECF volume through reduced low and high pressure baroreceptor sensitivity. In contrast, while the AVP responses to hypertonicity are maintained, the thirst responses seem to be reduced. It seems unlikely that the primary sensing 'osmoreceptor' neurons in the hypothalamus leading to AVP secretion or thirst would be differentially affected by age. Therefore the thirst deficit may result from changes with age in the more poorly defined pathways that bring thirst to consciousness. Following rehydration, thirst and AVP secretion are inhibited in young individuals thus avoiding overhydration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8438653 TI - The Sandoz Foundation for Gerontological Research. PMID- 8438654 TI - Biological significance of DNA methylation in the ageing process. AB - In order to understand the possible importance of DNA methylation in ageing, characteristics of its age-associated changes were examined in mouse and man. The total methylated deoxycytidine level in the genome decreased in the senescent period in mouse liver, but not in mouse brain and human liver. The examination of DNA methylation in each individual gene revealed that only a few genes showed alteration in the senescent phase while many genes change in the maturation period. The alterations were gene- and tissue-specific. Comparison of short living mouse and long-living man for the age-associated changes of the c-myc gene methylation revealed that the rate of change in mouse was about 20 times faster than that in man. This suggests a deep involvement of DNA methylation in ageing. Further investigations into the causes and consequences of the changes would clarify a basic mechanism of ageing. PMID- 8438655 TI - Studies on DNA repair defects in degenerative brain disease. AB - Using the alkaline filter elution technique we determined the induction and disappearance of single-strand breaks (SSB) in freshly isolated peripheral blood lymphocytes (PBL) from 43 Alzheimer disease (AD) patients and from 48 healthy, age- and sex-matched control subjects following in vitro exposure to N-ethyl-N nitrosourea (ENU), methyl methanesulphonate (MMS), or gamma (gamma)-radiation. No differences in SSB disappearance between AD patients and controls were observed after treatment of PBL with MMS or gamma-rays. After treatment with ENU, however, the amount of SSB disappearance was significantly lower in PBL from familial, but not in PBL from sporadic AD patients. ENU repair in PBL from neurological controls was comparable to that found in normal age-matched controls, indicating that the lower amount of ENU repair in familial AD patients is not a consequence of neuronal degeneration. These tentative findings are discussed in relation to the aetiology of AD. PMID- 8438656 TI - Toward understanding of the molecular basis of loss of neuronal plasticity in ageing. AB - Although there are several lines of evidence which suggest that neuronal plasticity decreases in some regions of both the central and peripheral nervous systems as well as in neuroendocrine tissues during development and ageing, the molecular mechanisms underlying loss of plasticity are largely unknown. To explore this question, we examined changes in expression profiles of neuronal growth-associated proteins (nGAPs) during ageing as well as the molecular regulatory mechanisms of their induction by nerve growth factor (NGF). SCG10, one of the nGAPs, is expressed in subsets of central neurons which maintain a high degree of plasticity in the adult, and is induced after neuronal deafferentation. This is a basis for analysing if SCG10 is involved in the remodelling of adult neurons during reactive synaptogenesis in diseased brains as well as in normal ageing. Studies of the induction of SCG10 by NGF in PC12 cells suggest that transcriptional inducible element(s) are present, at least in part, in the upstream region of the SCG10 gene. These studies of the regulation of nGAPs in ageing brains and neuroendocrine cells may yield new insights on reactivating neurites of partially degenerated neurons in the ageing brain. PMID- 8438657 TI - The importance of basic research in gerontology. PMID- 8438658 TI - Treatment of elderly hypertensives: some questions remain unanswered. PMID- 8438659 TI - A controlled trial of exercise by residents of old people's homes. AB - Regular exercise is widely advocated for the young and middle-aged, but less is heard about its relevance to elderly people. This study reports the findings of a controlled trial of seated exercise in residents of local authority homes for the elderly. Forty-nine residents aged 64-91 years volunteered for the 7-month project, and participated in either twice-weekly exercise or reminiscence sessions. Primary outcome measures were postural sway, flexibility of the spine and knees, hand-grip strength and functional capacity. The average (range of) attendance at the exercise sessions was 91% (64-100%), and at the reminiscence sessions was 86% (46-100%). By the end of the project, the change observed in the exercise group was significantly different from that of the reminiscence group in terms of grip strength (p < 0.02), spinal flexion (p < 0.001), chair-to-stand time (p < 0.001), activities of daily living (p < 0.05), and self-rating of depression (p < 0.01). Even very elderly residents of old peoples homes can benefit from participation in regular seated exercise and improve their functional capacity. PMID- 8438660 TI - Survey of 160 centenarians in Shanghai. AB - One hundred and sixty centenarians were discovered and followed up for 7 years (1982-88) in Shanghai. The proportion of centenarians in the population was non significantly greater in the urban than in the rural area and centenarians were in general increasing in both areas over the years. The factors promoting longevity were good medical care and benevolent attention from family members. Autopsy was performed in eight centenarians revealing the main causes of death as pneumonia and cancer. PMID- 8438661 TI - Quantification of the cardinal signs of parkinsonism and of associated disability in spouses of sufferers. AB - Work on the causation of idiopathic parkinsonism is limited by relying on gross clinical definition and lack of studies in the old. A prognostic index for parkinsonism, based on hypo/bradykinesia of gait, had considerably higher values in spouses of 20 aged suffers, who had been cohabiting for about half a century, than in 40 controls. Postural abnormality, measured by standing sway and foot separation during walking, was also greater in these spouses. Marked differences remained after correction for relevant covariates. A blinded rigidity rating was greater in the spouses of sufferers, tremor rating was not. The differences found are difficult to explain by selective mating, learned or reactive behaviour. This suggests that environmental causative influences operate in adult life. PMID- 8438662 TI - Is this walk normal? PMID- 8438663 TI - Percutaneous transluminal coronary angioplasty for post-infarction angina in elderly patients. AB - To assess the short-term outcome of percutaneous coronary angioplasty (PTCA) for post-infarction angina in elderly patients, we have retrospectively evaluated the results of 88 procedures of PTCA (98 lesions attempted), performed for post infarction angina (PIA), in 84 patients of > or = 65 years (elderly group), and compared the results obtained with those of 165 PTCAs (200 lesions attempted) in 161 patients of < 65 years old with PIA (young group). Angiographic success was obtained in 91 (93%) vs. 181 (91%) of lesions attempted in the groups, respectively. Complete revascularization was achieved in 54 (61%) patients treated in the elderly group vs. 106 (65%) in the young group. PTCA success was obtained in 78 (89%) procedures vs. 147 (89%) of both groups. No patients required emergency coronary surgery, two patients (2%) had a reinfarction in the elderly group vs. five patients (3%) in the young group, and two patients died (one in the elderly and one in the young group). In conclusion, PTCA for PIA in elderly patients provides a high clinical success rate with a low frequency of complications, similar to the results obtained in young patients. PMID- 8438664 TI - The association of age with gastric emptying. AB - Gastric emptying is important as a rate-limiting step in the absorption of orally administered drugs. Paracetamol absorption kinetics were used to compare gastric emptying in 19 fit elderly and 19 fit young volunteers. The results showed no significant difference in any of the derived parameters (t1/2abs, tlag and tmax) between the two groups. These results suggest that ageing does not impair this rate-limiting step in drug absorption. PMID- 8438665 TI - Is caffeine a factor in subjective insomnia of elderly people? AB - Subjective insomnia is more prevalent in elderly than in young populations. In order to examine the relationship between caffeine and sleep quality we studied 181 community-dwelling subjects over a wide age range and 53 elderly patients receiving continuing hospital care. Subjects completed a sleep questionnaire and data concerning smoking, alcohol, use of hypnotics and caffeine-containing substances were recorded. Late afternoon plasma caffeine concentrations were measured in a sub-group of 87 of the community-dwelling subjects and in the hospitalized patients. For the group as a whole, there was a significant negative correlation between age and coffee but not tea consumption (p < 0.001). A global score of sleep quality was significantly inversely related to age (p < 0.001). For the community-dwelling population, the median plasma caffeine concentration was 1.71 micrograms/ml (range 0.10-6.74) and showed a significant correlation with sleep quality (p < 0.05). In contrast, for the hospital dwelling population, median caffeine concentration was higher in patients reporting sleep problems than in those without (p < 0.05). Self-reported consumption of coffee and tea did not correlate with plasma caffeine concentrations. It is possible that people with poor sleep quality, residing in the community, are aware of the stimulatory effects of caffeine and lower their intake accordingly, whereas hospitalized elderly patients, who have less control over their environment, do not. PMID- 8438666 TI - The incidence of neglect phenomena and related disorders in patients with an acute right or left hemisphere stroke. AB - We studied 171 consecutive patients with an acute hemispheric stroke (69 right hemisphere, 102 left), at 2-3 days post-stroke. A standardized test battery, previously validated in patients with acute stroke, was used to detect a wide variety of neglect phenomena and related disorders. Visual neglect was found in 82% of assessable right hemisphere patients and 65% of left hemisphere patients. Hemi-inattention was found in 70% of right and 49% of left hemisphere strokes. Tactile extinction was found in 65% of right and 35% of left hemisphere patients; allaesthesia in 57% (right), and 11% (left); visual extinction in 23% (right) 2% (left). Anosognosia was found in 28% (right), and 5% (left); anosodiaphoria in 27% (right), and 2% (left); non-belonging in 36% (right) and 29% (left). Visual neglect occurred more commonly in left hemisphere stroke than previously reported. Although neglect phenomena and related disorders were associated with right hemisphere damage, it is possible that language difficulties obscured their presence in some patients with a left hemisphere stroke. PMID- 8438667 TI - Effect of exercise on cardiovascular ageing. AB - Ageing of the cardiovascular system presents several costly public health problems, loss of quality of life, dependency, and other various health hazards. Large declines of 0-24% per decade in cardiovascular function have been cited in the literature but no long-term longitudinal studies have been reported. Serially measured cardiovascular function was performed on 12 normal men, aged 44-79 years, at 0, 10, 15, 20 and 25 years. Over the same time period, daily exercise training data were reported monthly including mode, frequency, intensity, and duration. Although seven men developed some form of pathological disease, the total group's cardiovascular function remained 60% greater than the average of ten investigations. The overall decline in cardiovascular function (Vo2 max) was 13%, or 5% per decade, 45.4 ml.min-1.kg-1 to 39.5 ml.min-1.kg-1. In summary, cardiovascular function was one-half, or 0.24 ml.min-1.kg-1.year-1 of the 0.45 ml.min-1.kg-1.year-1 reported to be the average decline for ageing cited in the literature. PMID- 8438668 TI - Outcome of an integrated approach to the investigation of dizziness, falls and syncope in elderly patients referred to a 'syncope' clinic. AB - Sixty-five consecutive elderly patients (mean age 78 years) referred to a 'syncope' clinic over a six-month period were prospectively studied. Initial evaluation included ambulatory electrocardiography, carotid sinus massage before and after atropine and prolonged head-up tilt. Diagnostic criteria for causes of syncope were assigned at the beginning of the study. Overall, a diagnosis was attributed to symptoms in 92% of patients; overlap was present in a quarter. Diagnoses were cardioinhibitory carotid sinus syndrome (CSS; 5%), vasodepressor CSS (26%), mixed CSS (14%), orthostatic hypotension (32%), vasodepressor vasovagal syncope (11%), cardiac arrhythmia (21%), epilepsy (9%), cerebrovascular disease (6%) and others (12.5%). Sixty per cent of patients with vasodepressor CSS also had orthostatic hypotension or vasodepressor vasovagal syncope suggesting a common aetiology. Using an integrated approach incorporating head-up tilt and carotid sinus massage in a selected group of elderly patients referred to a 'syncope' clinic, the diagnostic yield was high. PMID- 8438669 TI - Falling and perimenopausal women. AB - The relationships between falling, fracture and bone density in perimenopausal women have not previously been explored. As part of a population-based screening programme for osteoporosis examining historical risk factors and bone mineral density, we have investigated risk factors for falling in 45-49-year-old women. Our results indicate that the risk of falling may be related to menopausal status, increased body weight, use of diuretics, self-reported arthritis and absence of car ownership. PMID- 8438670 TI - Review: abuse of elderly people in the domestic setting: a UK perspective. AB - Interest in, and concern about, the abuse of elderly people is growing rapidly. A study of the literature shows little research in the UK, but valuable indicators about risk factors and interventions from North America. One of the major problems has been definition and this paper distinguishes between different kinds of abuse. Conclusions are drawn about future research, and about the importance of records, assessment and multidisciplinary working, as well as the prevention of abuse. PMID- 8438671 TI - Glycosylated haemoglobin in the diagnosis of diabetes mellitus in elderly people. PMID- 8438672 TI - Adult day care for the demented elderly. PMID- 8438673 TI - Use of transdermal fentanyl for cancer pain management. PMID- 8438674 TI - The nicotine patch. PMID- 8438675 TI - Tattoo-acquired verruca plana. PMID- 8438676 TI - Prevention of hepatitis B virus infection. PMID- 8438677 TI - Peptic disease syndrome: should we treat H. pylori? PMID- 8438678 TI - Diary of a week in practice. PMID- 8438679 TI - Tension-type headaches. AB - Tension-type headaches are generally characterized by slowly progressive, dull, constant, nonpulsatile pain in the occipital and posterior neck or in a "headband" distribution. Episodic tension-type headaches occur fewer than 15 times a month, and chronic tension-type headaches occur more than 15 times a month for at least six months. Cranial radiography, computed tomographic scanning, electroencephalography and other adjunctive tests are unnecessary if the presentation is typical and the headache is not associated with seizure activity, mental status changes, neurologic deficits and other markers of potentially serious underlying disease. Treatment of episodic tension-type headaches may include topical heat or cold packs, exercise and other stress reduction techniques, mild analgesics, muscle relaxants and trigger-point injections. Some patients may benefit from antidepressants and individual or family counseling. PMID- 8438680 TI - Inflammatory bowel disease: Part II. Medical and surgical management. AB - Substantial advances have been made in the management of inflammatory bowel disease. Mesalamine and olsalazine are new anti-inflammatory agents that may serve as alternatives to corticosteroids and sulfasalazine, which have been the mainstays of medical therapy. These new agents are available in oral, enema and suppository forms. Brooke ileostomy remains the standard surgical treatment for advanced ulcerative pancolitis, but continent ileostomy procedures may be more cosmetically acceptable to selected patients. PMID- 8438681 TI - Managing Raynaud's phenomenon: a practical approach. AB - Raynaud's phenomenon is characterized by vasospasm of the digits, most commonly the fingers, although the toes, ears, nose and even the tip of the tongue may be involved. The disorder is commonly precipitated by exposure to cold, although vasoconstrictive drugs and emotional distress may be triggers. Patients with Raynaud's phenomenon should avoid these triggers. Behavioral therapies, including stress management, relaxation training and biofeedback, are effective in some patients. When lifestyle changes fail to control symptoms, medications may be prescribed to correct various underlying pathophysiologic mechanisms. Medications that may be effective include calcium channel blockers, angiotensin converting enzyme inhibitors, alpha-adrenergic blockers, pentoxifylline, dipyridamole and low-dose acetylsalicylic acid. PMID- 8438682 TI - Disorders of sexual desire: diagnosis and treatment of decreased libido. AB - Decreased libido is the most common concern expressed by patients when they discuss sexual issues with their physicians. The causes of decreased libido are complex and multifactorial, requiring attention and a careful history to isolate the primary origin. Although dissatisfaction with the relationship or marriage is the most common factor in patients with depressed desire, organic causes must also be considered. Physicians must remember that depressed libido is relative and depends on the patient's definition, not on an absolute standard of how frequently people do or should have sexual relations. PMID- 8438683 TI - Oral rehydration therapy. AB - Acute gastroenteritis is a leading cause of visits to physicians among children in the United States. Oral rehydration therapy has prevented or reversed dehydration among millions of children in developing countries. Although most U.S. health care providers are familiar with oral rehydration therapy, its proper use is still not widespread in industrialized nations. Viral pathogens in diarrheal illness can destroy absorptive cells at the intestinal villous tip while leaving secretory cells intact. Oral rehydration therapy takes advantage of the remaining intact absorptive cells, is less invasive than intravenous rehydration and allows parents to be involved in their children's care. This article outlines how to select patients for oral rehydration therapy, what fluids to use and how to implement therapy. PMID- 8438684 TI - Dioxin toxicity. Agency for Toxic Substances and Disease Registry. AB - Dioxins bioaccumulate in adipose tissue and can be found in most persons. Human exposure to dioxin is a concern because dioxins cause cancer in some animals. Chloracne is the only overt clinical sign of dioxin exposure in humans. PMID- 8438685 TI - Prevention of hepatitis B virus infection. AB - Hepatitis B virus infection is the most important cause of acute and chronic liver disease worldwide. The Immunization Practices Advisory Committee has proposed a comprehensive strategy to eliminate the transmission of hepatitis B virus in the United States. The three phases of this strategy are prevention of perinatal transmission of the hepatitis B virus, universal vaccination of all infants against hepatitis B virus infection and selected vaccination of high-risk adolescents and adults. Because family physicians provide obstetric, perinatal, adolescent and adult care, they can have a major influence on the success of this strategy. PMID- 8438686 TI - Diagnosis and treatment of pediatric foot deformities. AB - In children, the lower extremities have extremely wide variations of normal, including calcaneovalgus foot, metatarsus adductus and flatfoot. The first two conditions often resolve or improve spontaneously over time and may be considered abnormal if they persist into adulthood. Serial casting, splints and surgery are rarely necessary. Corrective shoes, orthotic inserts and some forms of splinting have not proved to be effective. The primary care physician must establish an early and correct diagnosis, perform a general screening examination to rule out accompanying musculoskeletal deformities, assess the conditions that may become disabling and require treatment, and reassure parents and family members when observation with close follow-up is the most appropriate course of action. PMID- 8438687 TI - Flumazenil: an antidote for benzodiazepine toxicity. AB - Flumazenil, a specific benzodiazepine antagonist, is useful in reversing the sedation and respiratory depression that often occur when benzodiazepines are administered to patients undergoing anesthesia or when patients have taken an intentional benzodiazepine overdose. Judicious use of flumazenil may provide useful diagnostic information and may obviate the need for mechanical ventilation and other invasive supportive measures. Although some controversy exists regarding the possible precipitation of seizure activity in the setting of mixed tricyclic antidepressant-benzodiazepine overdose, worldwide experience with flumazenil has validated its safety and efficacy. PMID- 8438688 TI - Update on food labeling. PMID- 8438689 TI - Preventive medicine: disease prevention. Recommended core educational guidelines for family practice residents. American Academy of Family Physicians. PMID- 8438691 TI - HIV telephone service for physicians. PMID- 8438690 TI - ADA issues management guidelines for lipid disorders in diabetics. PMID- 8438692 TI - Detection of reperfusion 30 and 60 minutes after coronary recanalization by a rapid new assay of creatine kinase isoforms in acute myocardial infarction. AB - We measured creatine kinase (CK) isoforms by a new immunoinhibition method to evaluate their usefulness in detecting early coronary reperfusion. Blood samples were collected at 15-minute intervals from 50 patients with acute myocardial infarction. CK isoforms were determined by a 10-minute immunoinhibition method with an autoanalyzer. Values for inhibited isoforms (MM3, MM2/2, and MB2/2) were divided by those of noninhibited isoforms (MM1, MM2/2, MB1, MB2/2, and BB) to calculate the isoform ratio. In the reperfused group the increase in the isoform ratio was 2.69 +/- 1.80 (SD) 30 minutes after reperfusion and 2.41 +/- 2.01 at 60 minutes, which was significantly higher than the corresponding values in the nonreperfused group (0.17 +/- 0.16 and 0.32 +/- 0.26, respectively). When an increase of 0.70 or more in the isoform ratio was used as the criterion for reperfusion, the sensitivity and specificity were 92% and 100% at 30 minutes and 100% and 100% at 60 minutes after recanalization, respectively. We conclude that the isoform ratio obtained by the new 10-minute assay of CK isoforms is useful for the noninvasive detection of reperfusion 30 and 60 minutes after recanalization in acute myocardial infarction. PMID- 8438693 TI - Myocardial technetium 99m sestamibi kinetics after reperfusion in a canine model. AB - Clinical sestamibi imaging protocols after reperfusion therapy are based on the premise that redistribution does not occur. However, animal studies that use punch biopsies or imaging have variably reported either some or no redistribution. This study was designed to (1) utilize implantable radiation detectors to determine whether sestamibi is redistributed after reperfusion, (2) accurately determine the time course, extent, and kinetics of the redistribution, and (3) determine whether sestamibi kinetics can be used to document reperfusion and salvage after a single dose of sestamibi. Twenty-five dogs were injected with 5.0 mCi of technetium 99m sestamibi and microspheres during circumflex occlusion, and reperfusion occurred within 5 minutes in group 1 (15-minute occlusion) and group 2 (1-hour occlusion). Group 3 was not reperfused. Sestamibi activities in the normal and occluded zones were monitored with radiation detectors for 2 hours, and serial gamma camera imaging and arterial blood sampling was begun. No dogs in group 1 and all dogs in groups 2 and 3 had infarcts as shown by triphenyltetrazolium chloride stain. The final occluded/normal zone technetium 99m activity ratio was significantly higher than the flow ratio at the time of sestamibi injection only in the group 1 dogs (0.51 +/- 0.05 vs 0.38 +/- 0.06, p = < 0.0001). In addition, the mean 2-hour fractional sestamibi clearance from the occluded/reperfused zone (0.03 +/- 0.02) was significantly slower in the group 1 dogs compared with normal zone clearance (0.09 +/- 0.01, p = 0.03). Gamma camera images demonstrated large posterior wall perfusion defects initially, which persisted 2 hours later with no visual evidence of redistribution in any of the reperfused dogs in groups 1 and 2. Thus in an experimental animal model under ideal conditions, sestambi is redistributed into reperfused viable myocardium; however, the amount of this redistribution is small and could not be perceived by visual image analysis. Sestamibi is not redistributed into reperfused nonviable myocardium or into nonreperfused myocardium. Therefore sestamibi kinetics after a single dose of tracer in an experimental animal model can be used to document reperfusion of viable myocardium but cannot differentiate reperfusion of the infarcted territory from nonreperfused infarcted myocardium. PMID- 8438694 TI - Plasma endothelin-1 in acute myocardial infarction with heart failure. AB - Endothelin-1 is a potent vasoconstricting substance that may aggravate circulatory dysfunction in acute myocardial infarction. In 59 patients with acute myocardial infarction peripheral venous blood was sampled, and endothelin-1 was measured by radioimmunoassay. Hemodynamic measurements were performed with a flow directed thermodilution catheter in 16 patients. Plasma endothelin-1 levels in Killip's classes were as follows: group I (no heart failure, n = 25), 1.97 +/- 0.69 pg/ml; group II (heart failure, n = 16), 2.74 +/- 1.02 pg/ml; group III (pulmonary edema, n = 13), 4.54 +/- 1.17 pg/ml; and group IV (cardiogenic shock, n = 5), 8.91 +/- 3.16 pg/ml (normal control group, n = 12: 1.51 +/- 0.39 pg/ml). There were significant correlations between the plasma endothelin-1 level and mean right atrial pressure (r = 0.554; p < 0.05), mean pulmonary artery pressure (r = 0.589; p < 0.02), and cardiac index (r = -0.534; p < 0.05). There were closer correlations between plasma endothelin-1 level and mean pulmonary artery wedge pressure (r = 0.678; p < 0.005) and total pulmonary vascular resistance (r = 0.831; p < 0.001). These results indicate that endothelin-1 is elevated in accordance with cardiac and pulmonary circulatory distress in patients with acute myocardial infarction, which may further aggravate circulatory dysfunction. PMID- 8438695 TI - Precordial ST segment depression in patients with Q wave inferior myocardial infarction: role of infarction-associated pericarditis. AB - To examine the diagnostic significance of precordial ST segment depression in Q wave inferior myocardial infarction, 157 consecutive patients were examined carefully by means of auscultation, ECG, and two-dimensional echocardiography. Precordial ST segment depression was transient (lasting < 72 hours from the onset of myocardial infarction) in 63 patients and persistent (> or = 72 hours) in 40. Twenty-eight patients with persistent, 19 patients with transient, and 14 patients without precordial ST segment depression had advanced asynergy (akinesia or dyskinesia) in the posterior segments, whereas 13 patients with persistent, six with transient, and six without precordial ST segment depression had pericardial rub. Patients with persistent precordial ST segment depression had a significantly higher incidence of severe wall motion abnormality (p < 0.01) and inflammation (p < 0.05) of the posterior wall than the other two groups. In 5 of 40 patients with persistent ST segment depression, pericardial rub was detected in the absence of advanced asynergy in the posterior segments. Although not highly sensitive, persistent precordial ST segment depression appeared to be a fairly specific indicator (specificity 92%) of concomitant posterior involvement with severe wall motion abnormality, inflammation, or both. PMID- 8438696 TI - Early heart rate variability alterations after acute myocardial infarction. AB - In order to assess early changes in heart rate variability, we studied 81 patients with acute myocardial infarction during the initial 24 hours after thrombolytic therapy. The standard deviation of the mean heart rate and the low (0 to 0.05 Hz), mid (0.05 to 0.20 Hz), and high (0.20 to 0.35 Hz) frequency band power were evaluated with 24-hour ECG Holter recordings. We found diminished variance in the time domain and reduced power spectrum in the frequency domain compared with a group of 41 normal subjects (p < 0.01). Patients with anterior infarction had significantly (p < 0.01) higher heart rates and lower heart rate variability values than patients with inferior infarction. Reduction in heart rate variability occurred within the first 8 hours in patients with anterior infarction; a significant fall (p < 0.03) was especially noted in the high frequency band after a decline in ST-segment elevation. Heart rate variability alterations in patients with inferior infarction were most evident in the final 8 hour interval. These findings may be viewed in terms of sympathovagal imbalance and may be related to clinical signs of intense autonomic nervous system activity that are observed early in the course of acute anterior and inferior myocardial infarction. PMID- 8438697 TI - Angioplasty of the septal perforators: acute outcome and long-term clinical efficacy. AB - Critical stenosis of a large septal perforator artery can cause significant myocardial ischemia. Since septal perforators are generally not accessible for bypass grafting, balloon angioplasty offers an excellent alternative for revascularization of these vessels. The short-term outcome and long-term clinical follow-up angioplasty of the septal perforator was evaluated retrospectively in 21 patients. Fourteen of the 21 (66%) had previous myocardial infarction, 9 of 21 (43%) had previous coronary bypass surgery, 10 of 21 (48%) had previous percutaneous transluminal coronary angioplasty (PTCA), and 6 of 21 (28%) had congestive heart failure. Additional PTCA of one or more vessels was undertaken in all patients. Primary success of PTCA of the septal perforator was achieved in 20 of 21 (95%) patients. The mean stenosis was improved from 89.8 +/- 10% to 18.4 +/- 11.7%. No acute closure, emergency coronary bypass, or myocardial infarction was observed or needed during hospital stay. At long-term follow-up (18 +/- 9 months), event-free survival was 95%. No cardiac death occurred. In 86% of cases, there was significant improvement in anginal class at 2 years. Five of the six patients with congestive heart failure showed marked improvement in functional class at 2 years. In conclusion, balloon angioplasty of the large septal perforator artery is technically feasible, with a high success rate, and does not increase the rate of acute complications of the procedure. Along with PTCA of other arteries, it provides long-term relief of angina in a majority of symptomatic patients with complex multivessel disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8438698 TI - Safety, success, and restenosis after elective coronary implantation of the Palmaz-Schatz stent in 100 patients at a single center. AB - We report the immediate safety, efficacy, and 6-month angiographic follow-up after elective implantation of the Palmaz-Schatz stent (Johnson & Johnson Interventional Systems, Warren, N.J.) in the first 100 consecutive patients at a single center. Patients with suitable cardiac anatomy and no contraindications to anticoagulation were prospectively entered into the study. One hundred two stents were successfully implanted in 99 patients. The mean diameter stenosis was 70% +/ 11% before implantation and was reduced to 20% +/- 11% after stent implantation. There were no deaths, Q-wave myocardial infarcts, urgent bypass operations, or strokes during the procedure or follow-up period. Stent thrombosis occurred in two patients; in both vessel patency was successfully accomplished by balloon angioplasty. There were three gastrointestinal hemorrhages, two of which required transfusion. Angiographic follow-up was performed in 98% of patients at 6.3 +/- 2.6 months after the procedure. Restenosis (> or = 50% stenosis within or immediately adjacent to the stent) occurred in 32%. Stent restenosis was associated with male sex (36% vs 7% for female subjects; p = 0.03) and stent implantation in a restenosis lesion (47% vs 25% for de novo lesions; p = 0.03); it was inversely associated with current cigarette smoking (0% vs 36% for nonsmokers; p = 0.02). In conclusion, the Palmaz-Schatz stent can be electively implanted with high success and low complication rates. The restenosis rate appears to be similar to that of balloon angioplasty. PMID- 8438699 TI - Assessment of myocardial fatty acid metabolism with positron emission tomography at rest and during dobutamine infusion in patients with coronary artery disease. AB - The myocardial clearance rate of C-11 palmitate as an index of fatty acid oxidation was assessed by means of positron emission tomography (PET) at rest and during dobutamine infusion in seven normal subjects and 10 patients with coronary artery disease. In the normal subjects the clearance half time was homogeneous in the left ventricle at rest and uniformly shortened during dobutamine infusion. In the myocardium at risk, clearance half time tends to be longer in the segments with an abnormal Q wave on ECG, exhibiting regional wall motion abnormality, and supplied by severely stenosed coronary arteries, particularly during dobutamine infusion. These data indicate that fatty acid oxidation may be decreased in infarcted myocardium and associated with regional asynergy. Such an abnormality was most striking in those with severe coronary stenosis during dobutamine infusion. We conclude that PET with the use of C-11 palmitate at rest and during dobutamine is a useful means of identifying impaired fatty acid oxidation and decreased metabolic reserve in patients with coronary artery disease. PMID- 8438700 TI - Cardiopulmonary exercise testing in syndrome X. AB - Patients with syndrome X have been found to have an abnormal coronary blood flow reserve. The physical performance during exercise, however, has been incompletely investigated. Cardiopulmonary exercise testing (CPX) is a reliable noninvasive method to provide indexes of lung, heart, circulation, and muscle functions. In 15 patients (10 women) with syndrome X and in age and sex-matched normal individuals, CPX was performed twice a day (8 AM and 4 PM) on two separate occasions 2 months apart. Time and oxygen consumption at peak exercise, at ventilatory anaerobic and electrocardiographic thresholds, as well as norepinephrine plasma concentrations at each work load and at peak exercise in both tests were obtained. In syndrome X in both evaluations, the 4 PM performance was characterized by an earlier onset of both ventilatory anaerobic and electrocardiographic thresholds despite lower values of VO2 and double-product, and by a greater peak ST segment depression despite similar total exercise time, VO2, and double-product. No difference between tests was found in the norepinephrine response to exercise. Normal subjects showed reproducible CPX and hormonal responses in the two tests. Thus these data may suggest a circadian variation of coronary vascular response to exercise in patients with syndrome X, leading to a lower ischemic threshold early in the afternoon. The parallel earlier onset of the ventilatory anaerobic threshold may reflect a concomitant abnormal muscular blood flow response (that is, vasoconstriction of working muscle arteries), suggesting a link between coronary and peripheral circulations. PMID- 8438701 TI - Diagnostic value of postexercise systolic blood pressure response for detecting coronary artery disease in patients with or without hypertension. AB - To evaluate the diagnostic value of the postexercise systolic blood pressure (SBP) response for detecting and evaluating the presence of coronary artery disease (CAD), treadmill testing was conducted in 130 subjects with normal blood pressure and 51 patients with hypertension, each of whom underwent selective coronary angiography. A total of 48 subjects with normal blood pressure and 27 patients with hypertension had no significant narrowing of the coronary artery (control subjects), whereas 82 subjects with normal blood pressure and 24 patients with hypertension had significant narrowing (patients with CAD). The postexercise SBP response was defined on the basis of the SBP ratio (i.e., the SBP at 3 minutes of recovery divided by that at peak exercise). An SBP ratio that exceeded 0.90 (cutoff point for discriminating control subjects from patients with CAD) was considered to be an abnormal SBP response. In the subjects with normal blood pressure, the abnormal SBP response identified CAD as accurately as did ST-segment depression. In the patients with hypertension, the diagnostic accuracy was increased significantly by combining the abnormal SBP response and ST-segment depression (p < 0.01). The SBP ratio increased with the number of diseased coronary arteries. Ten of the 14 patients with a narrowing of the left main coronary artery had an SBP ratio higher than 1.00. The postexercise SBP response may be useful for detecting CAD in patients with and without hypertension and for evaluating the severity of CAD. PMID- 8438702 TI - Heart rate variability and aerobic fitness. AB - Heart rate variability, a noninvasive marker of parasympathetic activity, diminishes with aging and is augmented after exercise training. Whether habitual exercise over time can attenuate this loss is unknown. This cross-sectional investigation compared 72 male runners, aged 15 to 83 to 72 age- and weight matched sedentary control subjects for the amplitude of their heart rate variability. Heart rate variability was assessed during rest while subjects were breathing at a rate of 6 breaths per minute and at an augmented tidal volume (tidal volume = 30% of vital capacity). Fitness levels were assessed with on line, open-circuit spirometry while subjects were performing an incremental stress test. Overall results between the two groups showed that the physically active group had significantly higher fitness levels (p < 0.001), which were associated with significantly higher levels of heart rate variability, when compared with their sedentary counterparts (p < 0.001). These findings provide suggestive evidence for habitual aerobic exercise as a beneficial modulator of heart rate variability in an aging population. PMID- 8438703 TI - Circadian rhythmicity of heart rate and QTc interval in diabetic autonomic neuropathy: implications for the mechanism of sudden death. AB - Patients with diabetic autonomic neuropathy (DAN) exhibit decreased heart rate variability (HRV) and are prone to sudden death. When HRV was used as an index of DAN, the circadian rhythmicity of heart rate and QT intervals was studied in 17 patients with diabetes who had varying degrees of DAN and 13 healthy control subjects. Heart rate and QT and QTc intervals for all subjects were found to exhibit a significant circadian periodicity. Heart rate was lowest and QT and QTc intervals were longest between midnight and 6:00 AM; heart rate increased and QT and QTc intervals shortened in the hours after waking. The diabetic group with more severe autonomic neuropathy (DAN+, HRV = 76 +/- 20 msec, n = 7) had significantly higher heart rate and shorter QT and QTc intervals compared with the diabetic group without autonomic neuropathy (DAN-, HRV = 120 +/- 13 msec, n = 10) or healthy control subjects (CT, HRV = 119 +/- 26 msec, n = 13). Twenty-four hour mean heart rate was 90 +/- 7 beats/min (range, 79 to 98 beats/min) for DAN+, 77 +/- 8 beats/min (range, 64 to 86 beats/min) for DAN- (DAN+ vs DAN-; p = 0.005), and 74 +/- 7 beats/min (range, 64 to 80 beats/min) for CT (DAN+ vs CT; p = 0.0004). Mean 24-hour QTc was 391 +/- 13 msec (range, 387 to 399) msec for DAN+, 417 +/- 19 msec (range, 413 to 425 msec) for DAN- (DAN+ vs DAN-; p = 0.01), and 412 +/- 28 msec (range, 408 to 419 msec) for CT (DAN+ vs CT; p = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8438704 TI - Initiation of atrial fibrillation in the Wolff-Parkinson-White syndrome: the importance of the accessory pathway. AB - Atrial fibrillation in the Wolff-Parkinson-White syndrome may be related to microreentry in the accessory pathway. If such is the case, catheter ablation of the accessory pathway should eliminate atrial fibrillation. Among 95 patients undergoing catheter ablation, 20 had atrial fibrillation during standard electrophysiologic study (atrial vulnerability) before ablation. There were 16 women and four men with a mean age of 32 years. Before ablation six patients required electrical cardioversion. Thirty minutes after ablation, 11 continued to have inducible atrial fibrillation. Atrial fibrillation terminated spontaneously in every patient after ablation. A control group of 20 patients with accessory pathway ablation had no inducible atrial fibrillation before or after ablation. Catheter ablation had no effect on atrial properties including functional refractory period (227 +/- 37 vs 215 +/- 29 msec before versus after ablation, mean +/- SD) or wavelength (7.4 +/- 3.2 vs 7.2 +/- 2.7 before versus after ablation). These data suggest that an intact accessory pathway is not necessary for initiation of atrial fibrillation in most patients with Wolff-Parkinson-White syndrome. A rapid ventricular response over the accessory pathway may facilitate the perpetuation of atrial fibrillation in persons prone to this arrhythmia. PMID- 8438705 TI - Reappraisal of radiofrequency ablation of multiple accessory pathways. AB - Complete electrophysiologic study and radiofrequency ablation were performed in 145 consecutive patients with Wolff-Parkinson-White syndrome. Presence of multiple accessory atrioventricular pathways was documented in 20 patients (13.8%); 17 had two, two had three, and one had four accessory pathways. Location of accessory pathways was posteroseptal in 18, left free wall in 15, right free wall in nine, and right midseptal in two. Of the 44 pathways, 36 were found during baseline electrophysiologic study and eight were found after successful ablation of the initially attempted pathways. After delivery 20 +/- 23 pulses (per patient) of radiofrequency energy (37 +/- 6 W, 70 +/- 30 seconds), 43 accessory pathways were ablated successfully without complications. Duration of the procedure (4.5 +/- 1.7 vs 3.7 +/- 1.6 hours, p < 0.05) and radiation exposure time (53 +/- 30 vs 38 +/- 18 minutes, p < 0.05) were longer in patients with multiple pathways, whereas the success rate (95% vs 95%, p > 0.05) and incidence of recurrent conduction (11% vs 11%, p > 0.05) were similar in patients with single or multiple accessory pathways. These findings confirmed that multiple accessory pathways were common in patients with Wolff-Parkinson-White syndrome, and these pathways could be ablated successfully by radiofrequency energy with a success rate comparable to that of a single accessory pathway. PMID- 8438706 TI - Hemostatic changes induced by percutaneous mitral valvuloplasty. AB - A study was conducted of hemostatic changes in 15 patients with mild-to-moderate rheumatic mitral stenosis who underwent percutaneous mitral balloon valvuloplasty (PMV). The patients were divided into two groups according to the degree of valve dilatation as evaluated by Doppler echocardiography before and 2 to 3 months after therapy: one group (n = 7) with suboptimal valvuloplasty (< 0.5 cm2) and one (n = 8) with optimal valvuloplasty (> or = 0.5 cm2). On the day of echocardiographic evaluation, hemostatic testing of the platelet, coagulation, and fibrinolytic systems was performed. Before PMV there were no differences in the hemodynamic and hemostatic variables between the two groups. No favorable hemostatic changes were achieved by PMV in the suboptimal group. In the optimal group, however, platelet-specific protein levels decreased after PMV; the mean levels of platelet factor 4 and beta-thromboglobulin were moderately elevated before and decreased after PMV from 38.5 +/- 22.2 to 8.13 +/- 5.08 ng/ml (p < 0.01) and from 132.5 +/- 78.6 to 38.8 +/- 19.5 ng/ml (p < 0.02), respectively. Coagulation and fibrinolytic systems were unchanged in this study. These data indicate that PMV produces favorable hemostatic effects when sufficient mitral valve dilatation is achieved. Analysis of our data also discloses that platelet activation plays an important role in the initial step of thrombus formation in patients with rheumatic mitral stenosis. PMID- 8438707 TI - Clinical significance of small left-to-right shunts after percutaneous mitral valvuloplasty. AB - Left-to-right shunt after percutaneous mitral valvuloplasty was evaluated by contrast echocardiography in 29 patients at 24 hours and at 1, 3, 6, and 9 months after the procedure. The patients were divided into two groups: in group A (13 patients) the double-balloon technique was used; in group B (16 patients) the Inoue single-balloon technique was used. The two groups were comparable in terms of age, gender, and mitral valve area before and after percutaneous mitral valvuloplasty. A left-to-right shunt was detected in all patients 24 hours after the procedure. At 1 month follow-up the shunt was present in 12 patients of group A (92%) and in 13 of group B (81%) with a statistically significant difference (p < 0.001). At 3 months the values were 7 (54%) in group A and 6 (37.5%) in group B (p < 0.05); at 6 months the values were 3 (23%) in group A and 3 (19%) in group B (NS). At 9 months a left-to-right shunt was no longer detectable in any of the patients in either group. The disappearance of the shunt could be related to a healing process of the atrial septal injury that occurs within a few months after percutaneous mitral valvuloplasty. This process seems to be more rapid in group B patients, probably because of the smaller lesion that is produced in the atrial septum by the passage of the Inoue balloon. PMID- 8438708 TI - Importance of abnormal lung perfusion in excessive exercise ventilation in chronic heart failure. AB - Whether excessive ventilatory response to exercise is related to the maldistribution of pulmonary blood flow was examined in 23 patients with chronic heart failure and nine age-matched normal subjects. With the use of technetium 99m macroaggregated albumin, the resting distribution of pulmonary blood flow was assessed by the scintigraphic counts ratio of upper to lower lung fields. The ventilatory response to exercise was assessed by the slope of the relationship between minute ventilation and carbon dioxide production during exercise. Eight patients (group A) had slope less than 33, the upper limit of the normal range, and 15 patients had slope of 33 or greater (group B). In group B pulmonary blood flow was distributed more to the upper lung, which made the counts ratio (60%) higher than in normal subjects (34%) or in patients in group A (38%). There was no significant difference in pulmonary flow distribution between normal subjects and patients in group A. In group B tidal volume did not increase during exercise as much as it did in normal subjects and in patients in group A; therefore, the respiratory pattern was rapid and shallow. Although the ratio of physiologic dead space to tidal volume fell by 20% during exercise in normal subjects and by 23% in patients in group A, it failed to decrease in patients in group B (-1%), which indicates a relative increase in dead space respiration during exercise. These data indicate that decreased lung compliance and regional ventilation-perfusion mismatch caused by pulmonary vascular and parenchymal abnormalities would play an important role in the excessive exercise ventilation in chronic heart failure. PMID- 8438709 TI - Arterial hemodynamics and cardiac effects of enoximone, dobutamine, and their combination in severe heart failure. AB - The acute systemic and regional hemodynamic effects of dobutamine (5, 10, and 15 micrograms/kg/min intravenously), of enoximone (1, 1.5, and 2 mg/kg intravenously), and of the dobutamine-enoximone combination were compared in eight patients with severe congestive heart failure. Dobutamine and enoximone similarly and dose-dependently increased cardiac index and decreased systemic vascular resistance, right atrial pressure, and mean capillary wedge pressure. Dobutamine, but not enoximone, increased heart rate after 10 and 15 micrograms/kg/min. The combination of the two drugs caused a greater increase in cardiac index and a greater decrease in total peripheral resistance than did each drug alone. In the forearm vascular bed, brachial blood flow and brachial artery diameter were increased by enoximone significantly and dose-dependently and by dobutamine only at 5 micrograms/kg/min. Finally, the combination of the two drugs increased brachial blood flow but not brachial artery diameter to a larger extent than enoximone alone. Hepatosplanchnic and renal blood flows were not altered by any of the treatments. These results indicate that (1) enoximone exerts a significantly greater muscular vasodilator action than dobutamine; (2) the dobutamine-enoximone combination potentiates the systemic and brachial vasodilator effects of each drug; and (3) high doses of dobutamine (10 and 15 micrograms/kg/min) improve hemodynamics through their positive inotropic and chronotropic effects, whereas at low doses (5 micrograms/kg/min) a peripheral vasodilation also contributes. PMID- 8438710 TI - Clinical and histologic features of alcohol drinkers with congestive heart failure. AB - To clarify the difference between alcoholic cardiomyopathy and dilated cardiomyopathy and to investigate the characteristics of alcoholic cardiomyopathy, right ventricular endomyocardial biopsy was performed, and the two diseases were compared clinically and histologically. Changes in the cardiothoracic ratio, cardiac index, and systolic blood pressure/end-systolic volume index were greater after treatment in patients with alcoholic cardiomyopathy than in patients with dilated cardiomyopathy. Histologically, myocytic hypertrophy, fibrosis, and nuclear change were less significant in the former than in the latter. Among patients with alcoholic cardiomyopathy, the cardiac index in those with less fibrosis was greater than in those with more fibrosis. Thus patients with alcoholic cardiomyopathy had more preserved and reversible cardiac function and fewer histologic changes than the patients with dilated cardiomyopathy. Reversibility of cardiac function in patients with alcoholic cardiomyopathy correlated inversely with the severity of histologic changes. PMID- 8438711 TI - Factors associated with heavy smoking among men and women: the physician delivered smoking intervention project. AB - As part of a randomized trial that compared the effects of three physician delivered smoking interventions on patients' long-term cessation rates, we examined factors associated with the extent of baseline cigarette smoking separately in 546 men and 715 women who were enrolled in this trial. Several baseline characteristics were significantly related to heavier (> or = 25 cigarettes per day) smoking after controlling for a variety of factors in multivariate analyses, which were performed separately for men and women. Among both men and women, extent of addictiveness to smoking and number of cigarettes smoked during periods of heaviest smoking were significantly related to extent of current cigarette smoking (p < 0.001). In addition, among men shortness of breath, lack of previous attempts to quit and lack of confidence in their ability to stop smoking were significantly related to current heavy cigarette smoking (p < 0.05). The results of this study in ambulatory outpatients suggest a profile of heavy cigarette smokers that may be used for the more effective delivery of targeted smoking intervention efforts. PMID- 8438712 TI - Superior vena cava occlusion and/or syndrome related to pacemaker leads. AB - Four cases of pacemaker-related SVC obstruction or syndrome are reported. While two of them lacked any symptom suggestive of SVC obstruction, the other two presented with mild symptoms. None of them received any treatment. One died from a cause unrelated to SVC obstruction, while the others presented no change in their clinical status. A review of the literature suggests that neither thrombotic nor fibrotic obstruction in patients with pacemaker leads is strictly related to the number of abandoned leads, the presence of severed leads, or the time elapsing from pacemaker implant. The diagnosis is clinically made and is confirmed by venography. Only one of the reported deaths is attributable to SVC obstruction. The remaining cases from the literature responded to treatment with heparin, thrombolytic agents, angioplasty, or surgery. PMID- 8438713 TI - Excimer laser coronary angioplasty in The Netherlands: preamble for a randomized study. AB - The immediate outcome of ELCA by XeCl excimer laser radiation is described in 53 patients who were selected to undergo ELCA from December 1990 to September 1991 in two centers that are currently performing ELCA in the Netherlands. Immediate success rates on the basis of visual assessment of the angiogram were as follows. Laser success (> 20% reduction of diameter stenosis after ELCA alone) was observed in 77% of patients, procedural success (< 50% residual stenosis after ELCA with or without adjunctive balloon dilatation [PTCA]) in 91%, and clinical success (procedural success without clinical complications) in 83% of patients. Quantitative coronary angiography by automated contour detection was performed in 31 patients who underwent ELCA in the Thoraxcenter. The minimal luminal diameter (mean +/- SD) of the treated coronary segments increased from 0.77 +/- 0.41 mm to 1.24 +/- 0.25 mm after ELCA and further to 1.67 +/- 0.29 mm after adjunctive PTCA in 25 patients. The present experience is put in perspective of results initially reported by other centers and compared with data from multicenter registries of ELCA. Finally, a short description is given of the design of a prospective, randomized trial of ELCA versus conventional PTCA (AMRO trial). PMID- 8438714 TI - Nitrogen-13 ammonia perfusion imaging: relation to metabolic imaging. AB - PET provides an advanced imaging technology that permits the accurate definition of regional tracer distribution. In combination with N-13 ammonia, PET allows for the sensitive and specific detection of coronary artery disease. Results of several studies indicate the superiority of this approach compared with standard thallium-201 tomographic imaging. In addition, regional blood flow can be accurately measured with N-13 ammonia PET, and this approach can be used in conjunction with pharmacologic stress imaging to quantify regional flow reserve. In combination with metabolic markers, N-13 ammonia is capable of assessing myocardial viability. Furthermore, the N-13 ammonia PET approach may differentiate among various forms of cardiomyopathy. More studies are needed to define the cost-benefit ratio of the N-13 ammonia PET technique for the management of patients with coronary artery disease or cardiomyopathy. PMID- 8438715 TI - White blood cell count, coronary heart disease, and death: the NHANES I Epidemiologic Follow-up Study. AB - To confirm the reported association of elevated WBC count with increased risk of CHD incidence and death in white men and to determine whether such associations exist for CHD incidence and death in women and blacks, data were examined from the NHANES I Epidemiologic Follow-up Study. Over a follow-up period of 7 to 16 years, WBC counts > 8100 cells/mm3 compared with WBC counts < 6600 cells/mm3 were associated with increased risk of CHD incidence in white men (RR = 1.31; 95% CL 1.07, 1.61) and in white women (RR = 1.31; 1.05, 1.63) aged 45 to 74 after adjustment for baseline risk factors. The association was found in white female but not in white male subjects who had never smoked. Increases in risk of death from all causes, cardiovascular diseases, and noncardiovascular diseases were also seen in all white men in the sample. RRs for death for all causes at ages 45 to 74, which compared the upper and lower strata of WBC counts, were 1.43 (95% CL 1.22, 1.68) in all white men and 1.33 (95% CL 1.00, 1.78) in subjects who had never smoked after adjustment for baseline risk factors. Similar increases in risk of death from all causes were seen in blacks aged 45 to 64 despite small sample size. Thus this analysis failed to clearly establish an increased risk of CHD incidence in white men with relatively elevated WBC counts who never smoked cigarettes, although such an association was evident in white women. The increased risk of death from all causes in men appeared to be only partially due to effects of smoking.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8438716 TI - Preexisting cardiovascular conditions and long-term prognosis after initial myocardial infarction: the Framingham Study. AB - Preexisting cardiovascular conditions (angina pectoris, intermittent claudication, stroke or transient ischemic attack, and congestive heart failure) were evaluated in relation to long-term prognosis after an initial MI in 828 subjects from the Framingham Heart Study. Preexisting angina pectoris and intermittent claudication in men were associated with increased risk of coronary mortality and recurrent MI, whereas congestive heart failure increased coronary mortality. In women, prior angina pectoris increased the risk of recurrent MI and congestive heart failure increased the coronary mortality. Adjusting for the major cardiovascular risk factors measured before MI, these results held for men but no significant adverse effects persisted in women. Among subjects who survived to return for subsequent examinations, only prior congestive heart failure in men increased the risk after adjusting for post-MI risk factors. In women who returned, angina pectoris and intermittent claudication were associated with poor post-MI prognosis. These results suggest that atherosclerosis is a diffuse disease of the circulatory system, and one in which post-MI prognosis is influenced by the presence of other preexisting cardiovascular conditions. Hence a patient who has an MI after prior expression of cardiovascular disease requires more vigorous preventive management. PMID- 8438717 TI - Clinical application of coronary flow velocity for stent placement during coronary angioplasty. PMID- 8438718 TI - Angiographic changes induced by intracoronary ultrasound imaging before and after coronary angioplasty. PMID- 8438719 TI - Intravascular ultrasound diagnosis of a coronary artery pseudoaneurysm following percutaneous transluminal coronary angioplasty. PMID- 8438720 TI - The surgical implications of endoluminal coronary ultrasound. PMID- 8438721 TI - Treatment of perioperative mammary artery graft spasm with nifedipine. PMID- 8438722 TI - Angina and ischemic electrocardiographic changes secondary to coronary arteriovenous fistula with abnormal basal and reserve coronary blood flow. PMID- 8438723 TI - Coronary angiodysplasia causing left ventricular shunt and myocardial ischemia. PMID- 8438724 TI - Protruding left ventricular thrombus formation following blunt chest trauma. PMID- 8438725 TI - Unruptured sinus of Valsalva aneurysm presenting with embolization. PMID- 8438726 TI - Radiofrequency catheter ablation of a right posterolateral atrioventricular accessory pathway with decremental conduction properties (Mahaim fiber). PMID- 8438727 TI - Delayed recurrence of atrioventricular block after radiofrequency ablation of atrioventricular node reentry: a word of caution. PMID- 8438728 TI - Infected transvenous permanent pacemakers: role of transesophageal echocardiography. PMID- 8438729 TI - Acute life-threatening hypertension following balloon angioplasty of native coarctation of the aorta. PMID- 8438730 TI - Immunohistochemical analysis of a human coronary artery exposed to excimer laser angioplasty in vivo: evidence for release of fibroblast growth factor at the site of injury. PMID- 8438731 TI - Transesophageal echocardiographic identification of a vegetation due to a jet lesion. PMID- 8438732 TI - Nonrheumatic valvular heart disease in the United States. PMID- 8438733 TI - Hemodynamic, mechanical, and metabolic determinants of thrombolytic efficacy: a theoretic framework for assessing the limitations of thrombolysis in patients with cardiogenic shock. AB - Although thrombolytic therapy has been shown to limit infarct size, preserve left ventricular function, and improve survival in most subgroups of patients with acute MI, a benefit has not been demonstrated in patients with clinical left ventricular dysfunction or overt cardiogenic shock before treatment is initiated. The reason(s) for the lack of benefit derived from thrombolytic therapy in these settings is unclear. Left ventricular dysfunction and overt cardiogenic shock are the result of extensive myocardial necrosis, typically in excess of 30% of the left ventricle, which progresses over time. The available data suggest that thrombolytic efficacy is decreased because of either hemodynamic, mechanical, or metabolic factors. As a result coronary patency is rarely achieved in a timely fashion, and if patency is achieved it typically is not maintained. The ability of mechanical revascularization by means of balloon angioplasty to reduce mortality suggests that reperfusion is a key determinant of outcome even among patients with large infarctions and early signs of left ventricular dysfunction. Thrombolytic therapy, which is widely available and extensively tested, represents the standard of care for patients with acute MI. Its apparent lack of efficacy in patients with congestive heart failure and cardiogenic shock is poorly understood. Further investigation must therefore be undertaken. PMID- 8438734 TI - Association of angiographically detected coronary artery disease with low levels of high-density lipoprotein cholesterol and systemic hypertension. AB - The prevalence of risk factors for atherosclerosis in 488 consecutive patients undergoing cardiac catheterization for the investigation of chest pain was compared with that in 868 subjects from a population sample. The presence and severity of angiographic coronary artery disease (CAD) (defined as mean diameter stenosis > 50%), total and high-density lipoprotein (HDL) cholesterol, triglycerides, history of systemic hypertension, smoking, diabetes mellitus, family history and drug therapy were assessed. Low HDL cholesterol (< 0.9 mmol/liter [35 mg/dl]) was more prevalent in patients with CAD than in the population sample in both men (44% [95% confidence interval 38 to 48] vs 21% [12 to 28]; p < 0.01) and women (12% [9 to 15] vs 1% [0 to 3]; p < 0.01). There were no differences in total cholesterol levels between these 2 groups. Total:HDL cholesterol ratios were significantly greater in patients with CAD. History of systemic hypertension was more prevalent in both men and women with CAD than in the population sample (47% [37 to 57] vs 20% [16 to 25] for men, and 31% [26 to 36] vs 21% [17 to 26] for women; p < 0.01). The prevalence of other risk factors was not significantly different between the 2 groups. In patients with CAD, the severity of disease was inversely correlated with levels of HDL cholesterol in both men and women (p < 0.01), and positively correlated with total cholesterol in men aged < 55 years (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8438735 TI - Coronary surgery and coronary angioplasty in patients with two-vessel coronary artery disease. AB - There is uncertainty regarding the selection between coronary artery surgery and angioplasty in many patients with coronary artery disease, especially in those with 2-vessel disease. Whereas randomized trials will provide the best possible and most detailed data comparing therapy in these patients, clinical data bases may be used to provide a current perspective. The purpose of this study was to compare the long-term outcome of patients with 2-vessel coronary artery disease undergoing coronary surgery or angioplasty at Emory University hospitals in the years 1984 and 1985. Data on all patients with 2-vessel disease diagnosed at Emory University who underwent elective angioplasty or coronary surgery in the years 1984 and 1985 were compared. Categoric variables were analyzed by chi square and continuous variables by unpaired t test. Survival was determined by the Kaplan-Meier method and differences in survival by the Mantel-Cox method. Determinants of survival were determined by Cox model analysis. There were 415 angioplasty patients and 454 surgical patients. Surgical patients were older and had more frequent systemic hypertension, diabetes mellitus, prior myocardial infarction, severe angina and congestive failure, and more significant narrowing in the left anterior descending coronary artery, totally occluded vessels and left ventricular dysfunction than did angioplasty patients. Complete revascularization was achieved more often in surgical patients. There was no difference in Q-wave myocardial infarction in the hospital. No angioplasty patient died compared with 1.1% of surgical patients (p = 0.03). Whereas 5-year survival was 93% in angioplasty patients and 89% in surgical patients (p = 0.11), there was no difference in risk-adjusted survival.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8438736 TI - Comparison of death rates from acute myocardial infarction in a single hospital in two different periods (1977-1978 versus 1988-1989). AB - The in-hospital prognosis of patients with definite acute myocardial infarction (AMI) treated at the University Medical Center in Marburg, Germany, was retrospectively evaluated for the years 1977 to 1978 and 1988 to 1989. Diagnosis of AMI was established in 357 patients (251 men, 106 women) in 1977 to 1978 and in 338 patients (240 men, 98 women) in 1988 to 1989. Overall in-hospital death rate increased from 19.6% (1977 to 1978) to 28.7% (1988 to 1989) (p < 0.01). Median ages of both groups were comparable. Patients treated in 1988 to 1989 had a higher prevalence of arterial hypertension (p < 0.001), hypercholesterolemia (p < 0.0001), reinfarction (p < 0.01), and successful resuscitation before hospital arrival (p < 0.0002). Univariate risk factor evaluation suggested the following unfavorable prognostic variables: age, successful resuscitation before hospital arrival, diabetes mellitus, reinfarction, and female sex. A favorable prognosis was associated with a history of smoking, higher serum cholesterol concentration and thrombolysis. Logistic regression analysis identified age, smoking, serum cholesterol concentration, and the combination of treatment period with either successful resuscitation before hospital arrival, or diabetes mellitus, as independent variables of in-hospital prognosis. In conclusion, the apparent increase of in-hospital death rate between 1977 to 1978 and 1988 to 1989 could mainly be attributed to differences in the 2 study groups. PMID- 8438737 TI - Retreatment with alteplase for early signs of reocclusion after thrombolysis. The European Cooperative Study Group. AB - Recurrent chest pain with new ST-segment elevation was observed in 26 of 652 patients (4%) with myocardial infarction in a clinical trial of alteplase (recombinant tissue-type plasminogen activator; 100 mg) and aspirin with or without heparin. Clinical and electrocardiographic signs of reocclusion were treated with a second dose of alteplase: 50 mg in 20 patients with signs of reocclusion < or = 24 hours after initial therapy, and 100 mg in 5 patients with signs between 24 and 77 hours, and in 1 patient with early signs of reocclusion. Pain and ST changes disappeared within 100 minutes (median 50). D-dimer determinations in 15 patients were increased, indicating activation of the coagulation system. Signs of reocclusion occurred despite adequate anticoagulation with heparin in 5 of 11 patients in whom coagulation measurements were available. No excess bleeding was observed in patients who received a second dose of alteplase. Retreatment with alteplase is feasible and provides an alternative for angioplasty in patients with clinical and electrocardiographic signs of reocclusion early after thrombolytic therapy. PMID- 8438738 TI - Use of carbon-11 acetate and dynamic positron emission tomography to assess regional myocardial oxygen consumption in patients with acute myocardial infarction receiving thrombolysis or coronary angioplasty. AB - Carbon-11 (C-11) acetate has been introduced for the noninvasive measurements of myocardial oxygen consumption. This study was designed to assess regional C-11 acetate clearance in patients with acute myocardial infarction. Thirty-one patients were studied within 8 days of acute myocardial infarction. C-11 acetate washout-rate constants were significantly lower in the infarct territory than in the remote myocardium (p < 0.008). The scintigraphic measurements correlated with heart rate-blood pressure product in the remote as well as infarct areas (0.52 and 0.48, respectively). There was no significant correlation to left ventricular ejection fraction. C-11 washout rates were significantly affected by beta receptor therapy as assessed by multiple regression analysis. Thus, C-11 acetate kinetics allow noninvasive characterization of regional myocardial oxygen demand, which may be useful in assessing the extent of myocardial injury and myocardial oxygen demand of remote myocardium. PMID- 8438739 TI - Diagnostic accuracy of seismocardiography compared with electrocardiography for the anatomic and physiologic diagnosis of coronary artery disease during exercise testing. AB - A multicenter study was performed to compare the diagnostic accuracy of a new technique, seismocardiography, with that of electrocardiography for physiologically and anatomically significant ischemic coronary artery disease (CAD) during exercise stress testing. Five participating centers enrolled 129 patients who had simultaneous seismocardiograms and 12-lead electrocardiograms at the time of their exercise treadmill stress tests. Two different definitions of CAD were used: anatomic and physiologically significant disease. The presence of anatomically significant CAD (> or = 50% diameter stenosis) was documented by coronary angiography. Physiologically significant CAD was defined as present in the same 129 patients when coronary arteriography (> or = 50% diameter stenosis) and thallium-201 scintigraphy (defect on initial postexercise images) were both abnormal. Seismocardiography had a significantly better sensitivity for detecting anatomic CAD than did electrocardiography (73 vs 48%; p < 0.001), without loss of specificity (78 vs 80%; p = NS). Exercise seismocardiography added significant incremental diagnostic information beyond that provided by exercise electrocardiography. Seismocardiography was more sensitive (without less specificity) in women and in patients who did not achieve maximal predicted heart rate. In patients with physiologically significant CAD, the seismocardiogram was also significantly more sensitive (78%) than was the electrocardiogram (55%) (p < 0.02), without loss of specificity (84 vs 74%). Seismocardiography significantly improved sensitivity for the detection of anatomic and physiologic CAD. It is easy to perform and may be a clinically useful adjunct in exercise stress testing. PMID- 8438740 TI - Quantitative analysis of factors influencing late lumen loss and restenosis after directional coronary atherectomy. AB - Although encouraging initial results have been demonstrated after directional atherectomy, the mechanisms and predictors of late lumen loss and restenosis after this procedure have not been evaluated. To examine these issues, clinical and angiographic follow-up were obtained in 262 (96%) and 212 (77%) of 274 patients undergoing successful directional coronary atherectomy. Symptom recurrence developed in 87 (33%) patients and angiographic restenosis was found in 93 (44%). Restenosis was highest in re-stenotic lesions in saphenous vein grafts (78% [95% confidence interval (CI): 56 to 100%]) and lowest in new-onset lesions in the left anterior descending (27% [95% CI: 15 to 39%]) and circumflex (14% [95% CI: 0 to 43%]) coronary arteries. Residual lumen diameter immediately after atherectomy was smaller in re-stenotic lesions (p = 0.002) and in lesions > or = 10 mm in length (p = 0.02). Late lumen loss was associated with the minimal lumen diameter immediately after atherectomy (p < 0.001), saphenous vein graft lesion location (p = 0.008), and male gender (p = 0.02). Re-stenotic lesions (p < 0.001), lesions > or = 10 mm in length (p = 0.018), saphenous vein graft lesion location (p = 0.025) and male gender (p = 0.045) were independent predictors for restenosis. It is concluded that restenosis after directional atherectomy is related both to factors resulting in a suboptimal initial result and to factors contributing to excessive late lumen loss. These results may have implications for lesion selection in patients undergoing directional coronary atherectomy. PMID- 8438741 TI - Propafenone versus sotalol for suppression of recurrent symptomatic atrial fibrillation. AB - Because conventional antiarrhythmic therapy is often ineffective in maintaining sinus rhythm or is associated with adverse side effects in patients with atrial fibrillation (AF), there is a clinical need to test newer agents. One hundred patients with AF who had unsuccessful therapy with 1.9 +/- 1.0 type IA antiarrhythmic agents were randomized to receive either propafenone (n = 50) or sotalol (n = 50). Patients were stratified into 4 groups based on AF pattern (chronic vs paroxysmal) and left atrial size (large [> or = 4.5 cm] vs small [< 4.5]). The proportion of patients remaining in sinus rhythm on each agent was calculated for each group by the Kaplan-Meier method. For patients randomized to propafenone, 46 +/- 8%, 41 +/- 8% and 30 +/- 8% remained in sinus rhythm at 3, 6 and 12 months, respectively, after cardioversion. A similar proportion of patients treated with sotalol remained in sinus rhythm at follow-up (49 +/- 7%, 46 +/- 8% and 37 +/- 8% at 3, 6 and 12 months, respectively; p = NS). The proportion of patients remaining in sinus rhythm on propafenone and sotalol was not dependent on arrhythmia pattern or left atrial dimension. Except for constipation that occurred more frequently in patients treated with propafenone, adverse side effects were equally distributed between the 2 therapies. Two patients receiving sotalol died during follow-up. Propafenone and sotalol, 2 new antiarrhythmic agents, were found to be equally effective in maintaining sinus rhythm in 100 patients with recurrent AF. Response rates were not affected by arrhythmia pattern, left atrial size or unsuccessful prior drug therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8438742 TI - Risks of developing supraventricular and ventricular tachyarrhythmias after implantation of a cardioverter-defibrillator, and timing the activation of arrhythmia termination therapies. AB - The clinical courses of 39 consecutive recipients (mean age 61 +/- 12 years, and mean left ventricular ejection fraction 0.32 +/- 0.15) of an automatic implantable cardioverter-defibrillator (ICD) were examined to determine the risks of developing ventricular tachycardia (VT) and supraventricular tachyarrhythmias (SVT) after surgery, with ventricular response rates fulfilling ICD detection criteria. ICD system leads were implanted by thoracotomy in 25 patients and by using nonthoracotomy lead systems in 14. Six patients (18%) developed SVT after surgery, whereas 14 (36%) developed sustained VT. The median times to the development of both SVT and VT were 2 days. By actuarial analysis, the probability of developing VT after surgery was significantly greater than that of SVT during hospitalization (p = 0.04). This significant excess of postoperative VT over SVT was most marked in patients aged < or = 61 years, those who received nonthoracotomy rather than epicardial lead systems, those who presented with VT rather than ventricular fibrillation, and those who received > 20 intraoperative defibrillation shocks. These observations recommend the activation of ICD therapies immediately after implantation. PMID- 8438743 TI - Doppler echocardiographic assessment of an impedance-based dual-chamber rate responsive pacemaker. AB - Rate-responsive pacing allows patients with chronotropic incompetence to achieve more physiologic heart rate responses to exercise. One sensor currently being investigated uses impedance-derived measurements of changes in right ventricular stroke volume to alter the pacing rate. Correlation of pacemaker-derived measurements of stroke volume with an accepted method of stroke volume measurement has not been performed. The relative changes in impedance-derived stroke volume were compared in 10 patients with an impedance-based dual-chamber rate-responsive pacemaker (Precept DR, Cardiac Pacemakers, Inc.) with simultaneous Doppler echocardiographic measurements of right and left ventricular stroke volume. These comparisons were made during pacing at 2 heart rates (70 and 100 beats/min) and 3 AV intervals (150, 200 and 250 ms) while in a supine resting state, during lower body negative pressure to -30 mm Hg, and while performing 25% maximal handgrip. Pacemaker-derived stroke volume decreased by 7 to 11% and Doppler time-velocity integral measurements decreased by 14 to 19% in response to an increase in pacing rate (p = NS). There was also no significant difference by either technique in the mean stroke volume change when the atrioventricular interval was varied. Both techniques detected a decrease in stroke volume during lower body negative pressure, ranging from -7 to -20% by pacemaker, and -17 to 38% by Doppler. Overall, the pacemaker stroke volume measurements responded in an appropriate direction to each intervention, signaling the pacemaker's ability to detect directional change in stroke volume. The Precept DR may aid in the programming of parameters such as atrioventricular interval and heart rate by allowing for optimization of stroke volume in individual patients. PMID- 8438744 TI - Comparative trial of doxazosin and atenolol on cardiovascular risk reduction in systemic hypertension. The Alpha Beta Canada Trial Group. AB - The impact of treating hypertension on coronary artery disease has been less than anticipated from epidemiologic studies of cardiovascular risk factors. It has been suggested that adverse effects on lipids of traditional diuretic or beta blocker regimens may diminish the potential benefits of antihypertensive therapy. Patients with mild to moderate systemic hypertension and normal serum lipids (n = 191) were randomly assigned to doxazosin or atenolol. After dose titration to goal diastolic blood pressure of < or = 90 mm Hg, patients continued treatment for a further 24 weeks. The principal outcome measurement was overall coronary artery disease risk using the Framingham formula. Relative risk of coronary artery disease was reduced to 92.4% of baseline (p = 0.144) for evaluable patients taking atenolol (n = 71), and to 74.6% (p = 0.0001) for patients taking doxazosin (n = 51): atenolol versus doxazosin, p = 0.0074. In patients who met the strict Framingham criteria for age, total cholesterol and high density lipoprotein cholesterol, the relative risk of coronary artery disease for patients taking atenolol (n = 23) was reduced to 86.2% of baseline (p = 0.082), and to 67.4% (p = 0.0004) for patients taking doxazosin (n = 18): atenolol versus doxazosin, p = 0.049. Alpha blockade with doxazosin was more effective than beta blockade with atenolol in reducing the risk of coronary artery disease in hypertensive patients because of the beneficial effects of doxazosin on high density lipoprotein cholesterol. Overall withdrawal rate was greater in the alpha blocker group because of a lower response rate and more adverse events. PMID- 8438745 TI - Hemodynamic response to orthostatic stress in the elderly with systolic systemic hypertension before and after long-term thiazide therapy. AB - The hemodynamic effects of orthostatic stress in elderly subjects with systolic hypertension were studied before and after long-term hydrochlorothiazide therapy (50 mg daily). Sixteen nondiabetic men aged 70 +/- 1 (SE) years participated in the study initially, and 12 completed 1 year of therapy. Patients underwent 45 degrees head-up incline on a tilt table before, after 1 month and after 1 year of therapy. Hemodynamic variables were measured in the following situations: (1) the supine position, (2) immediately after completion of passive 45 degrees head-up position at 0 minute, (3) at 15 minutes in the tilted state while patients performed intermittent foot movements to minimize gravitational pooling and simulate the standing position outside the laboratory, and (4) after returning to the supine position. Systolic and diastolic blood pressure (BP) decreased significantly after 1 month of therapy, and this reduction was maintained up to 1 year in all aforementioned body positions, with the exception of diastolic BP at 0 minute of tilt, which was significant at 1 year only. Before therapy was begun, there was a significant reduction in systolic BP immediately after completion of tilting; however, this was statistically insignificant both at 1 month and 1 year of therapy. Thus, the data may help dispel the concern of exacerbating the hypotensive response to orthostatic stress in patients with systolic hypertension after long-term thiazide diuretic therapy. PMID- 8438746 TI - Frequency and severity of intravascular hemolysis after left-sided cardiac valve replacement with Medtronic Hall and St. Jude Medical prostheses, and influence of prosthetic type, position, size and number. AB - Intravascular hemolysis occurs often in patients with mechanical heart valve prostheses, but in most cases is of mild degree and subclinical. The severity of hemolysis is reported to be related to the type, position and size of prostheses used, as well as the presence of valve malfunction. Hemolysis was evaluated in 170 patients with St. Jude Medical (SJM) and 80 patients with Medtronic Hall (MH) prostheses, with normal mechanical function. The presence and severity of hemolysis was assessed on the basis of serum lactic dehydrogenase, serum haptoglobin, blood hemoglobin and reticulocyte levels as well as the presence of schistocytes. Overall, patients with SJM prostheses had greater frequency (51.2 vs 18.7%, p < 0.005) and severity (p < 0.005) of hemolysis than patients with MH prostheses, irrespective of position and size. No patient had decompensated anemia. The frequency of hemolysis was similar in both groups with double-valve replacement, whereas severity was greater with SJM than MH prostheses (p < 0.001). The number and position of the prostheses were correlated with severity of hemolysis: Double-valve replacement and mitral position were correlated with greater hemolysis than single-valve replacement (p < 0.01) and aortic position (p < 0.01). Valve size, cardiac rhythm and time from operation did not correlate either with frequency or severity of hemolysis. It is concluded that in normally functioning SJM and MH prostheses: (1) hemolysis is frequent but never severe; (2) SJM demonstrates greater frequency and severity when compared with MH valve; and (3) number, position, but not size, significantly affect the severity of hemolysis. PMID- 8438747 TI - Usefulness of metoprolol for unexplained syncope and positive response to tilt testing in young persons. AB - The efficacy of intravenous metoprolol in preventing symptoms during a repeat tilt test was compared with the outcome of chronic oral treatment in 21 patients (14 female, 7 male), age 8 to 20 years (mean 13 +/- 3) with unexplained syncope (> or = 1 episode) and a positive response to tilt testing. A positive response was defined as the development of either syncope or presyncope. During the initial tilt test, a positive response occurred during baseline (14 patients) or isoproterenol (0.03 to 0.1 microgram/kg/min) infusion (7 patients) with a cardioinhibitory (1 patient), vasodepressor (5 patients) or mixed (15 patients) pattern. Metoprolol (0.1 to 0.2 mg/kg) was administered intravenously. During the repeat tilt test, response was negative in 18 patients, including 11 of 14 patients with a positive response in the baseline and 7 of 7 patients with a positive response during isoproterenol infusion. Metoprolol (0.8 to 2.8 mg/kg/day) was administered orally to 15 patients for an average of 10 months. Symptoms were absent (7 patients) or improved (2 patients); metoprolol was discontinued because of adverse effects (3 patients) or recurrence of symptoms (3 patients). In 7 of 12 patients with a negative response and 2 of 3 patients with a positive response after intravenous metoprolol, oral administration of metoprolol prevented or improved symptoms without adverse effects. Many young patients (60%) with recurrent syncope obtained symptomatic improvement from chronic oral metoprolol treatment without adverse effects; repeat tilt testing after intravenous metoprolol did not appear to offer any additional information than would have been obtained from a trial of chronic oral treatment. PMID- 8438748 TI - Relation between patent foramen ovale and unexplained stroke. AB - To better elucidate the possible role of the patent foramen ovale (PFO) in patients with unexplained stroke, the relation between the incidence of stroke and 3 characteristics of PFO (timing, magnitude of appearance of echocardiographic contrast in the left atrium, and morphology of the atrial septum) was analyzed. Twenty-nine patients with unexplained stroke and 28 without stroke were compared. A significant relation was only found between the incidence of cerebrovascular accident and positive contrast echocardiography in patients with early and massive passage of contrast in the left atrium (6 of 29 [21%] in the stroke group vs 0 of 28 [0%] in the control group; p < 0.05). An abnormal morphology of the foramen ovale was found more frequently in patients with PFO than in those without PFO (9 of 13 [69%] vs 1 of 44 [2%]; p < 0.001). The results suggest the use of timing and quantification of contrast appearance in the left atrium during contrast transesophageal echocardiography, and that paradoxical embolism through a PFO is a possible mechanism of cryptogenic stroke only if there is a massive passage of contrast through an abnormal foramen ovale. PMID- 8438749 TI - Ninety-three hearts > or = 90 years of age. PMID- 8438750 TI - Effect of enalapril on congestive heart failure treated with diuretics in elderly patients with prior myocardial infarction and normal left ventricular ejection fraction. PMID- 8438751 TI - Diagnosis of patent foramen ovale by transesophageal contrast echocardiography. PMID- 8438752 TI - Aortic biomechanical properties in pediatric patients with the Marfan syndrome, and the effects of atenolol. PMID- 8438753 TI - Aortic dimensions in tall men and women. PMID- 8438754 TI - Heart rate and blood pressure consequences of an afternoon SIESTA (Snooze-Induced Excitation of Sympathetic Triggered Activity). PMID- 8438755 TI - Left ventricular diastolic function by Doppler echocardiography in relation to hormonal replacement therapy in healthy postmenopausal women. PMID- 8438756 TI - Mitral regurgitation and death while awaiting cardiac transplantation. PMID- 8438757 TI - Emergency simultaneous transthoracic and epicardial defibrillation for refractory ventricular fibrillation during routine implantable cardioverter-defibrillator testing in the operating room. PMID- 8438758 TI - Unilateral pulsatile varicose veins from tricuspid regurgitation. PMID- 8438759 TI - Massive perigraft aortic aneurysm late after composite graft replacement of the ascending aorta and aortic valve in the Marfan syndrome. PMID- 8438760 TI - The best anti-heart failure agent will be a lipid-lowering agent. PMID- 8438761 TI - Age-associated changes in left ventricular diastolic performance during isometric stress. PMID- 8438762 TI - Control of arginine vasopressin and congestive heart failure. PMID- 8438763 TI - Determinants of post-cardiac transplantation hypercholesterolemia. PMID- 8438764 TI - Sex-hormone-binding globulin and protein-energy malnutrition indexes as indicators of nutritional status in women with anorexia nervosa. AB - Serum sex-hormone-binding globulin (SHBG), transferrin, prealbumin, retinol binding protein, and ceruloplasmin concentrations were evaluated in 12 women with anorexia nervosa before and after weight gain and in 12 healthy women with normal weight. The serum SHBG concentrations were higher in patients with anorexia nervosa before weight gain than in control subjects and they returned to the normal range after weight gain. The changes of SHBG concentrations were not associated with any change in plasma testosterone, estradiol, or free thyroxin concentrations. The body mass index in our patients after weight gain was lower than in control subjects. Prealbumin, retinol-binding protein, ceruloplasmin, and transferrin in anorectic patients before weight gain did not differ from those of the control subjects and increased after weight gain. The changes of serum SHBG concentrations in patients with anorexia nervosa during weight gain make SHBG determination a reliable index of nutritional status in this type of eating disorder. PMID- 8438765 TI - Determination of body composition--a comparison of dual-energy x-ray absorptiometry and hydrodensitometry. AB - Determination of body composition by dual-energy x-ray absorptiometry (DEXA) was evaluated in healthy men, by using underwater weighing (UWW), skinfold thickness measurement, and bioimpedance analysis. There were strong correlations between percent body fat obtained by all techniques, but DEXA gave significantly lower values (P < 0.001). The influence of differences in bone mineral density (BMD) on fat content determined by UWW was also studied. The individual differences between UWW and DEXA fat estimates were calculated and there was a negative correlation with BMD (r = -0.50, P < 0.05). There was also a negative correlation between body fat by UWW and BMD (r = -0.71, P < 0.01) in the subjects with lowest fat by DEXA, indicating that high or low BMD gave false values by UWW. In conclusion, DEXA and UWW provide complementary information and a combination of these techniques seems to offer new opportunities in evaluations of body composition. PMID- 8438766 TI - Waist-hip ratio is a poor predictor of changes in visceral fat. AB - Magnetic resonance imaging was used to study the effect of weight loss on three fat depots: the visceral and subcutaneous abdominal depots and the subcutaneous depot at trochanter level. Changes in fat depots were compared with changes in circumference measures and the waist-hip ratio (WHR) in obese men (n = 38) and women (n = 40). Mean weight loss was (mean +/- SD) 12.9 +/- 3.5 kg (P < 0.001). The proportional reduction of fat was largest in the visceral depot (men 40%, women 33%). Less fat was lost subcutaneously, especially at trochanter level (men 29%, women 26%). WHR decreased significantly in both sexes (P < 0.001). Change in WHR was not significantly related to the absolute reduction in visceral fat. Total body-fat loss showed a stronger association with subcutaneous fat loss than with visceral fat loss. The findings suggest that fat distribution may change with weight loss, particularly by the loss of visceral fat, but changes in WHR are not appropriate for evaluating changes in this fat depot. PMID- 8438767 TI - Growth and body composition of periurban Guatemalan children in relation to zinc status: a cross-sectional study. AB - In a study of periurban Guatemalan school-children (89 males, 73 females) aged 81.5 +/- 7.0 mo (mean +/- SD), height, weight, arm circumference, and triceps skinfold-thickness (TSF) measurements were examined in relation to plasma and hair zinc concentrations, plasma and red blood cell alkaline phosphatase activities, recognition thresholds for salt (RTS), delayed-cutaneous hypersensitivity response to seven recall skin test antigens, and cognitive measures. Children were stunted [median height-for-age (HA) Z score -1.49] but not wasted [median weight-for-height (WH) Z score 0.20], with median midarm muscle area (MAMA) and midarm-fat area (MAFA) Z scores of -0.57 and -0.35, respectively. Of the children, 63.5% of males and 44.1% of females had hair zinc < 1.68 mumol/g (P < 0.05); 12.3% of males and 1.5% of females had plasma zinc < 10.71 mumol/L (P < 0.05). Children with hair zinc < 1.68 mumol/g had higher (P < 0.05) medians for WA Z and WH Z scores, RTS, and phytic acid intake than did those with hair zinc > or = 1.68 mumol/g. Zinc status explained some of the variance in growth (HA, WA, and WH Z scores), body composition (MAFA Z scores), and taste acuity. Suboptimal zinc status arose partly from diets low in readily available zinc. PMID- 8438768 TI - Growth and body composition of periurban Guatemalan children in relation to zinc status: a longitudinal zinc intervention trial. AB - Changes in growth, body composition, and zinc indexes were evaluated after 25 wk in a double-blind zinc-supplementation study of 162 periurban Guatemalan children aged 81.5 +/- 7.0 mo (mean +/- SD). Children receiving the zinc supplement (10 mg Zn/d as amino acid chelate) for 90.1 +/- 9.2 d had higher mean fasting plasma zinc (16.2 +/- 2.9 vs 14.9 +/- 2.1 mumol/L, P < 0.01), a greater increase in median triceps skinfold Z score (0.50 vs 0.38, P < 0.05), and a smaller deficit in median midarm circumference (MAC) Z score (-0.03 vs -0.20, P < 0.05) compared with the placebo group. Initial hair zinc classified as < 1.68 and > 1.68 mumol/g was the only laboratory variable that explained some of the variance in final Z scores of midarm-muscle area (P < 0.05) and MAC (P < 0.01). Children responded to the zinc supplement with changes in indexes of body composition rather than growth. PMID- 8438769 TI - Evidence of energy sparing in Gambian women during pregnancy: a longitudinal study using whole-body calorimetry. AB - Components of daily energy expenditure were measured serially by whole-body calorimetry in Gambian women before pregnancy and at 6, 12, 18, 24, 30, and 36 wk gestation. Weight gain was (mean +/- SD) 6.8 +/- 2.8 kg, fat deposition was 2.0 +/- 2.5 kg and lean tissue deposition was 5.0 +/- 2.5 kg. Basal metabolic rate (BMR) was depressed during the first 18 wk of gestation, causing total cumulative maintenance costs by week 36 to be 8.4 MJ. Individual responses to pregnancy correlated with changes in body mass (36 wk: delta BMR vs delta weight; r = 0.60, P < 0.01 delta BMR vs delta LBM; r = 0.62, P < 0.01). There was no significant increase in the cost of treadmill exercise (0% slope: F = 0.71, P = 0.64; 5% slope: F = 1.97, P = 0.10), 24-h energy expenditure (F = 0.72, P = 0.64), activity or diet-induced thermogenesis (F = 1.02, P = 0.43), during pregnancy in spite of body weight gain. Total metabolic costs over 36 wk were 144 MJ (fetus 43 MJ, fat deposition 92 MJ, cumulative maintenance costs 8.4 MJ). These were far lower than reported for well-nourished Western populations. PMID- 8438770 TI - Biological determinants of pregnancy weight gain in a Filipino population. AB - Patterns of pregnancy weight gain and predictors of first trimester and total weight gain were investigated in a sample of 1367 women from Cebu, Philippines, with pregnancy intervals of < 2 y. The mean total weight gain based on actual measurements of prepregnant weight was 8.4 kg. Controlling for gestational week when weight was measured, multivariate-regression models predicted higher first trimester weight gain with higher parity, lower prepregnant body mass index (BMI), and longer nonpregnant intervals. Higher total weight gain was associated with longer nonpregnant intervals, lower prepregnant BMI, taller maternal stature, and relatively high dietary energy intakes. Lactation into the third trimester of pregnancy and maternal age over 35 y had significant negative effects on total weight gain. Given the importance of maternal weight gain in predicting birth outcome, this study provides information on modifiable risk factors that should be considered when developing maternal-infant health policy and programs. PMID- 8438771 TI - Fat preference and adherence to a reduced-fat diet. AB - The nature and mechanisms of altered food acceptability during adherence to a reduced-fat diet have not been characterized. These issues were assessed in healthy adults assigned to a reduced-fat diet excluding discretionary fat sources (n = 9), a similar diet permitting fat-modified products (n = 9) or no dietary modification (n = 9). Sensory responses to foods, body composition, and dietary intake were determined at baseline, monthly during 12 wk of diet adherence, and 12 followup wk. Marked and comparable reductions of fat intake were achieved in the experimental groups. Hedonic (ie, pleasantness) ratings for high-fat foods and preferred fat content of selected foods declined, but only in the group deprived of sensory exposure to fats. Thus, the frequency of sensory exposure to fats exerts a stronger influence on hedonic ratings of foods containing fat than total fat intake. The hedonic shift may promote long-term compliance with a reduced-fat diet. PMID- 8438772 TI - Saturated fatty acid chain length and positional distribution in infant formula: effects on growth and plasma lipids and ketones in piglets. AB - Human milk contains a large proportion of palmitic acid (16:0) with > 70% esterified to the center sn-2 position of the milk triglyceride. Infant formulas often use 8:0 + 10:0 [medium-chain triglyceride (MCT)] or 12:0 + 14:0 (coconut oil) as the saturated fat. The effect of formula saturated fatty acid composition; 8:0 + 10:0, 12:0 + 14:0, or 16:0 from palm oil or synthesized triglyceride containing predominantly sn-2 16:0 on plasma lipids and fatty acids was studied in piglets. Although the formulas contained similar 18:1 and 18:2n-6, plasma lipid percentages of 18:1 and 18:2n-6 were higher in piglets fed the formula with MCT or coconut oil rather than the formulas with 16:0, or sow milk. The sn-2 16:0 of the synthesized triglyceride had unique properties. Specifically, piglets fed synthesized triglyceride had significantly higher cholesteryl ester 16:0 identical to that in piglets fed sow milk and higher plasma total and high-density-lipoprotein cholesterol than piglets fed the other formulas. PMID- 8438773 TI - Oxidation of low-density lipoproteins: intraindividual variability and the effect of dietary linoleate supplementation. AB - Low-density lipoprotein (LDL) oxidation was measured in vitro to determine intraindividual variability and to relate oxidation to linoleic acid enrichment. Intraindividual variability was determined for eight subjects on 3 consecutive days after 14 d on a fixed diet. Coefficients of variation were 7.49 +/- 1.50%, 6.58 +/- 1.16%, and 4.58 +/- 0.77% for oxidation rate, lag time, and diene concentration, respectively. In the second study 12 normolipidemic men consumed a daily diet supplement containing 35 g linoleate-rich oil in one period and 35 g oleate-rich oil in the other period (2 x 3 wk crossover). LDL oxidized faster after the linoleate diet than after the oleate diet (mean +/- SE: 16.42 +/- 0.85 and 13.16 +/- 0.68 nmol diene.mg LDL protein-1.min-1, respectively, P < 0.02) and produced more conjugated diene (416 +/- 12.60 and 379.29 +/- 11.06 nmol/mg protein, respectively, P < 0.05) in proportion to the increase in LDL linoleate (r = 0.698, P < 0.001 and r = 0.618, P < 0.01 for rate and diene concentration, respectively). Lag time before onset of oxidation was not significantly altered by the linoleate-rich diet. PMID- 8438774 TI - Correlation of lactose maldigestion, lactose intolerance, and milk intolerance. AB - Lactose digestion and tolerance were evaluated in 164 African Americans ranging in age from 12 to 40 y who claimed intolerance to one cup (240 mL) or less of milk. With use of a breath-hydrogen test with 25 g lactose as test dose and the presence or absence of symptoms, 50% of the subjects were classified as lactose maldigesters and intolerant, 8% were maldigesters but tolerant, 15% were digesters but intolerant, and 27% were digesters and tolerant. Forty-five subjects from the lactose maldigesting and intolerant group were further tested for milk intolerance in a double-blind study. Sixty-seven percent of the subjects reacted appropriately to the presence or absence of lactose in ingested milk whereas 33% reported symptoms to both low-lactose milk and milk containing lactose. The results suggest that the cause of milk intolerance in as many as one third of African Americans claiming symptoms after ingestion of a moderate amount of milk cannot be its lactose content. PMID- 8438775 TI - Effect of beta-carotene on immunological indexes in healthy male smokers. AB - To evaluate the immunomodulatory effects of beta-carotene we performed a randomized, double-blind trial in healthy male cigarette smokers. Lymphocyte subsets in peripheral blood were assessed by using double labeling with monoclonal antibodies before and after 14 wk beta-carotene (20 mg/d; n = 21) or placebo (n = 24) supplements. In addition we measured the ex vivo phytohemagglutinin and concanavalin A induced lymphocyte proliferation in a separate group (23 placebo, 24 beta-carotene). The beta-carotene and placebo groups were comparable on all initial characteristics. During the intervention plasma concentrations of beta-carotene increased 13-fold in the treatment group whereas retinol concentrations remained constant. Beta-carotene had no effect on lymphocyte subpopulations in peripheral blood. After treatment the beta-carotene group showed 12% higher PHA-induced lymphocyte proliferations than the placebo group (P = 0.02). For ConA induced proliferations no significant difference was observed. These results suggest that supplementary beta-carotene can moderately enhance certain aspects of immune response in healthy male cigarette smokers. PMID- 8438776 TI - A 1-y trial of the effect of high-selenium bread on selenium concentrations in blood and toenails. AB - The concentration of selenium in toenail clippings and blood reflects dietary intake better than does intake calculated from dietary data because of the highly variable selenium concentration in different samples of the same food. However, the time course of selenium intake in relation to subsequent concentrations in toenail clippings is unclear. Therefore, 12 males were fed high-dose (4.91 mumol Se/d), medium-dose (2.61 mumol Se/d), or control (0.41 mumol Se/d) whole-wheat bread for 1 y and the concentration of selenium was measured in toenail clippings collected every 12 wk for 2 y. Toenail selenium concentration was unaffected by dietary intake in the previous 3 mo and appeared to provide a time-integrated measure of intake over a period of 26-52 wk. Use of selenium concentration in toenail clippings may be an alternative to blood when a measure of long-term average intake is desired. The absence of a short-term effect of diet on toenail selenium concentration also makes this a useful marker of intake in retrospective studies. PMID- 8438777 TI - Day-to-day variation in iron-status indexes in elderly women. AB - Day-to-day variability in biochemical indicators of iron status in well-hydrated and healthy women 70-79 y old (n = 10) was determined. Venous blood was collected on 4 nonconsecutive days during a 2-wk period. Analytical (sigma 2 rep) and biological (sigma 2 fd) variance components were computed based on a previously established scheme in younger adults. These two variance components were summed to obtain the total day-to-day variability (sigma 2 fd). Our results indicate that biological variation contributed most to the intraindividual variation. We calculated that sampling once for most iron indexes and twice for plasma transferrin receptors in elderly individuals is adequate to accurately determine these indexes whereas serum iron and transferrin saturation, indexes with high CVfd, require seven and eight measurements, respectively. These data, compared with previously published data in younger adults, demonstrate that aging is associated with a decreased variation in some indexes of iron status such as serum ferritin. PMID- 8438778 TI - Hepatic utilization of exogenous nucleotide precursors for restoration of ATP after cold ischemia in rats. AB - The study objective was to assess hepatic utilization of exogenous adenosine or adenine to enhance ATP recovery in rat liver after cold ischemia. ATP was measured noninvasively by 31P nuclear magnetic resonance (NMR) in perfused livers before and after 18 h of cold ischemia. The hepatocellular concentration of ATP during the initial postischemic reperfusion without adenosine or adenine coinfusion was 60% of that in fresh liver. The ATP increased significantly (P < 0.001) to 139% and 82% of baseline in postischemic livers coinfused for 90 min with adenosine or adenine (final concentration, 1 mmol/L), respectively. Less than 0.5% of the excess adenosine was catabolized to uric acid. In conclusion, adenosine and, to a lesser extent, adenine are salvaged by liver after extended cold ischemia to enhance ATP restoration. Provision of these ATP precursors, as components of an enteral formulation may facilitate the repletion of liver ATP and foster early resumption of liver function after an ischemic insult. PMID- 8438779 TI - Essential fatty acids, plasma cholesterol, and fat-soluble vitamins in subjects with age-related maculopathy and matched control subjects. AB - A matched-control study of plasma retinol, alpha-tocopherol, carotenoid, and cholesterol concentrations and the polyunsaturated fatty acid content of plasma and erythrocyte phospholipids was undertaken in 65 elderly patients with age related maculopathy and 65 control subjects matched for age and sex. Despite the high statistical power of the study and large variations between subjects in the variables under consideration, no significant differences were noted between patients and control subjects. However, several statistically significant differences were noted between male and female subjects independent of their classification with maculopathy or as controls and age: plasma cholesterol, total phospholipids, alpha-tocopherol, and beta-cryptoxanthin concentrations were higher in females than in males. The mean plasma cholesterol concentration for the upper tertile of the whole sample was 7.6 mmol/L. Plasma concentrations of total carotenoids, alpha-carotene, and beta-carotene, but not alpha-tocopherol, were significantly lower in smokers than in non-smokers. The results of this study do not provide any evidence in favor of changing the dietary intake of polyunsaturated fatty acids or fat-soluble vitamins to protect against age related maculopathy. PMID- 8438780 TI - Rapid catch-up growth of children fed a high-protein diet during convalescence from shigellosis. AB - Sixty-nine children age 2-5 y, convalescing from shigellosis in a randomized clinical trial were fed either a high-protein diet containing 628 kJ.kg-1.d-1 with 15% of total energy as protein, or a standard-protein diet that was isoenergetic but with 7.5% of total energy as protein for 21 d. Children fed the high-protein diet showed a significant increase in height (1.02 +/- 0.44 cm; mean +/- SD) compared with the children who were fed the standard-protein diet (0.69 +/- 0.34 cm; P < 0.001). Similarly, increases in body weight were 1.25 +/- 0.48 vs 0.86 +/- 0.48 kg for the high-protein and the standard-protein diet, respectively (P < 0.001). The mean increases of serum proteins were also significantly higher in the high-protein group (P < 0.01). These results indicate that increasing the protein content of the diet during convalescence from shigellosis in children leads to more rapid catch-up growth. PMID- 8438781 TI - Effect of isoenergetic intake of three or nine meals on plasma lipoproteins and glucose metabolism. AB - To investigate the effects of meal frequency on plasma lipid and carbohydrate metabolism, 19 healthy normocholesterolemic free-living men and women consumed their usual diet as three or nine meals per day in random order for 2 wk each. There was no significant difference in macronutrient intake. Compared with the three-meal/d diet, nine meals per day reduced fasting plasma total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol by 6.5% (P < 0.005), 8.1% (P < 0.005), and 4.1% (P < 0.05), respectively. Body weight, fasting triglycerides, apolipoproteins A-I and B, and the LDL-HDL cholesterol ratios were not different for the two diets, as were 24-h urinary C peptide-creatinine ratios and insulin-glucose response to a glucose load. The insulin-glucose curve measured over 3 h in the evening after the evening meal was flatter for the nine meals, but the areas under the curves were not significantly different. Increasing meal frequency while maintaining a constant nutrient intake produces a small but significant decrease in LDL cholesterol in normolipidemic free-living subjects. PMID- 8438782 TI - The thermogenic role of exercise in the treatment of morbid obesity. PMID- 8438783 TI - L-cysteine in metabolic acidosis of low-birth-weight infants. PMID- 8438784 TI - Diagnosis of urinary tract infection. A modern procrustean bed. PMID- 8438785 TI - Plasma cocaethylene concentrations in patients treated in the emergency room or trauma unit. AB - Cocaethylene and cocaine concentrations were measured by high-pressure liquid chromatography in the plasma of 18 patients whose corresponding blood demonstrated ethanol and whose urine contained either benzoylecgonine and/or cocaine on screening for illicit drug use. Although sixteen patients had suffered trauma, only 15 were admitted to the trauma unit. Three patients were seen only in the emergency room. Both cocaethylene and cocaine were detected together in the plasma of 10 patients and not all in 5 patients. In two patients, cocaine was found without cocaethylene, and in one patient cocaethylene was present without cocaine. For the entire series, cocaine concentrations showed significant correlation with those of cocaethylene. Plasma cocaethylene concentrations varied and were as high as 784 nmol/L (249 micrograms/L), and those of cocaine were as high as 1,455 nmol/L (441 micrograms/L). Before this study, published measurements of cocaethylene have been limited almost exclusively to postmortem specimens. PMID- 8438786 TI - A modified screening procedure to detect pyruvate kinase deficiency. AB - Beutler's screening procedure was used to detect pyruvate kinase deficiency in the local population. In this test, hemolysate and the reagent mixture are incubated and then placed at a spot on filter paper to be examined for fluorescence. Complete nonfluorescence marks the reaction endpoint, and fluorescence beyond 30 minutes indicates pyruvate kinase deficiency. It was difficult to determine this endpoint due to uneven sedimentation of unhemolyzed red cells on the spot. In this modified technique, the leukocyte-depleted red cell suspension was frozen and thawed for complete red cell lysis before being used for the test. Using both techniques, 493 health individuals and 126 anemic patients were screened for pyruvate kinase deficiency. By the conventional technique, 3.7% remained fluorescent after 30 minutes, whereas by the modified technique, none were fluorescent after 30 minutes. Quantitative assay indicated that all samples had pyruvate kinase activity levels greater than the lower limit of the reference range. We also demonstrated that blood samples from individuals with thalassemia trait were primarily responsible for the aberrant results from the conventional screening procedure. PMID- 8438787 TI - Investigation of bone marrow lymphocyte subsets in normal, reactive, and neoplastic states using paraffin-embedded biopsy specimens. AB - Bone marrow lymphocyte subsets in normal and reactive states and in neoplastic diseases involving the marrow were investigated with a select panel of monoclonal antibodies reactive on routinely processed, paraffin-embedded trephine biopsy material. In all cases, the antibodies beta F1 and UCHL1 (CD45RO) stained virtually equal numbers of T cells (reactive and neoplastic), whereas antibody OPD4 stained only about one half of this number of T cells. Antibody L26 (CD20) stained B cells (reactive and neoplastic) in all specimens. The T-cell to B-cell ratio in the normal marrow was between 4:1 and 5:1, and a significant increase in T-cell numbers was observed in reactive and myelodysplastic states. A significant increase in B-cell numbers, however, was seen only in marrow infiltrated by B cell lymphoma. Bone marrow exhibiting infiltrates of B-cell lymphoma, acute leukemia, or myeloproliferative disorders showed normal or decreased numbers of T cells. These findings show that antibodies UCHL1, beta F1, and L26 can be used to determine the numbers of B and T lymphocytes in paraffin-embedded, formalin-fixed bone marrow specimens and thus may help to distinguish reactive T lymphocytosis from B-cell lymphoma. PMID- 8438788 TI - Determination of low-molecular-weight heparin by Heptest on the automated coagulation laboratory system. AB - The manual Heptest for measuring low-molecular-weight heparin fractions was applied to a fully automated, coagulation-dedicated analyzer, the Automated Coagulation Laboratory 300 Plus. The clot-based assay mode of the instrument was used, which operates on the principle of light scattering. Undiluted plasmas and the original reagents of the Heptest kit were used. Also, the 2-minute incubation time of the manual procedure was maintained. Automation reduced plasma and reagent volumes by about one half. As a result of the high precision of the automated procedure, single determinations suffice, and 18 plasma samples can be analyzed in about 8 minutes. Coefficients of variation were 1.0% to 3.2% for within-run and 1.9% to 6.0% for inter-run analyses. Analytical recovery was 98% to 104%. Comparisons of 132 samples between the two procedures yielded an R value of 0.974 for activity expression in seconds and 0.945 for U/mL. Several low molecular-weight heparin fractions were tested. PMID- 8438789 TI - Evidence of a cold immunoglobulin M autoantibody against 78-kD platelet glycoprotein in a case of EDTA-dependent pseudothrombocytopenia. AB - Pseudothrombocytopenia is a phenomenon in which the electronic count shows spuriously low platelet counts in subjects with normal platelet levels. The mechanism of anticoagulant-dependent pseudothrombocytopenia appears to involve cold reactive agglutinins against platelet antigens. The authors report a case of EDTA-dependent pseudothrombocytopenia with evidence of a cold immunoglobulin M antibody against 78-kD platelet membrane glycoprotein (GP). Cell counts were performed by Coulter Counter S-Plus VI (Coulter, Hialeah, FL) in the following anticoagulants: EDTA, Na-citrate, and citrate-theophylline-adenosine dipyridamole. Anti-platelet antibodies and platelet membrane GP antigens were assayed by an immunofluorescence technique as described by Van dem Borne in 1978. An immunoglobulin M/lambda anti-platelet antibody was found to react in serum as well as in plasma EDTA at room temperature, but not at 37 degrees C. This antibody appeared to be directed against GP78 membrane antigen because this antigen was not detectable by immunofluorescence in platelets collected in EDTA and Na-citrate anticoagulant, whereas a fluorescence signal was revealed in platelets collected in citrate-theophylline-adenosine-dipyridamole. This evidence was confirmed by platelet clumping inhibition tests in which target platelets were pretreated with anti-GP monoclonal antibodies. Clumping in the presence of pseudothrombocytopenia serum was inhibited by anti-GP78kD and anti-GPIIb/IIIa but not by anti-Ib. In this case, GP78 appears to be involved in platelet clumping, together with IIb/IIIa complex. The partial inhibition of the phenomenon observed in citrate-theophylline-adenosine-dipyridamole is probably related to a lower expression of the membrane antigens in platelets collected in this anticoagulant. PMID- 8438790 TI - Laboratory considerations in the diagnosis and management of Lyme borreliosis. PMID- 8438791 TI - Estrogen and progesterone receptor content in human thyroid disease. AB - Recent studies have confirmed the presence of estrogen and progesterone receptors in many benign and malignant thyroid tumors, but their clinical significance is unclear. The estrogen and progesterone receptor content of 135 thyroid lesions was assayed prospectively from 1980 through 1986 using the dextran-coated charcoal method. The cases included 30 papillary, 13 follicular, 6 medullary, and 2 Hurthle cell carcinomas. Thirty-two follicular adenomas, 45 goiters, and 7 cases of thyroiditis also were studied. Estrogen receptor protein was positive (> or = 2 fmol/mg) in 46% of the cases, with no clear statistical predilection related to the type or size of the thyroid lesion, age, or sex. Progesterone receptor protein was positive (> or = 10 fmol/mg) in 51% of the cases, with the highest median values obtained in papillary carcinomas, particularly in male patients and women older than 50 years. Metastases at presentation, noted in 28 of 51 carcinomas, were unrelated to receptor content. Mean follow-up of 55 months in 48 patients with various carcinomas yielded 12 cases with late metastases, which were similarly unrelated to receptor content. Although estrogen receptors are commonly detectable in thyroid lesions, they have no clear relationship to presenting clinical or pathologic features or, in cases of carcinoma, to subsequent metastatic potential. The role of progesterone activity in papillary carcinoma and in goiter merits more investigation. PMID- 8438792 TI - Cytologic evaluation of serous effusions. Processing techniques and optimal number of smears for routine preparation. AB - A double-blind retrospective review of 90 pleural and ascitic fluids was performed to determine the optimal number of smears necessary to produce an accurate evaluation, and to analyze the utility of different preparation techniques. Each case had four Papanicolaou-stained smears (two alcohol fixed and two Saccomanno fixed) and one Diff-Quik-stained, air-dried smear. Forty cases originally were reported as positive (37 adenocarcinoma, 1 lymphoma, and 2 Pneumocystis carinii) and 50 were reported as negative. The results showed that the diagnostic yield of evaluating five smears compared with three (one of each preparation) is identical. Air-dried smears were the most sensitive in identifying malignant cells and infectious organisms. It is concluded that (1) the diagnostic accuracy is enhanced by the use of several preparation techniques to include air-dried smears and (2) when variable processing methods are used, the evaluation of more than three smears does not increase the diagnostic yield. PMID- 8438793 TI - Flow cytometric and image analyses of colorectal adenocarcinomas. A comparative study with clinical correlations. AB - Quantitative DNA measurements were performed in 183 colorectal carcinomas by image and flow cytometric analyses of paraffin-embedded tissue. Flow cytometric analysis yielded more diploid tumors compared with image analysis, which identified more tetraploid tumors. Histogram patterns were concordant in 115 tumors (66%); the discordant cases were primarily tumors interpreted as diploid by flow cytometric analysis but were aneuploid or tetraploid by image analysis. Linear regression analysis of DNA indices of concordant samples showed good correlation but only moderate correlation for the entire group. Both techniques revealed more aneuploid tumors in the distal colon and rectum than in the proximal colon. Diploid tumors were associated with a better prognosis; however, tetraploid tumors behaved like aneuploid tumors by flow cytometric analysis but like diploid tumors by image analysis. When stratified by stage, the prognostic value of diploid tumors was seen in stages A and B disease by image analysis only and in stage C disease by flow cytometric analysis only, possibly because of the small cohort size. The S-phase fraction (mean value, 16.8% +/- 9.9%) was higher in aneuploid than in diploid tumors, but no relationship to prognosis was seen. Flow cytometric and image analyses are useful to study ploidy of colorectal carcinoma from archival material. However, important discordant observations reflecting differences in characteristics of the two techniques should be considered, depending on which technique is used. PMID- 8438794 TI - Coexistence of anti-neutrophil cytoplasmic antibody-associated glomerulonephritis and membranous glomerulopathy. AB - The association of renal Wegener's granulomatosis with other glomerular diseases is very rare. A case of anti-neutrophil cytoplasmic antibody-associated necrotizing glomerulonephritis superimposed on a membranous glomerulopathy in a patient with systemic Wegener's granulomatosis is reported. Renal failure was corrected by immunosuppressive therapy treatment, but a non-nephrotic-range proteinuria persisted for several months. The association of membranous glomerulopathy with anti-glomerular basement membrane disease and other autoimmune diseases is well described; however, anti-neutrophil cytoplasmic antibody-associated vasculitis superimposed on membranous glomerulopathy has not been reported previously. PMID- 8438795 TI - Perilous times in pathology education. PMID- 8438796 TI - Perilous times in pathology education. PMID- 8438797 TI - Perilous times in pathology education. PMID- 8438798 TI - Syphilis screen at delivery: a need for uniform guidelines. PMID- 8438799 TI - Cystic fibrosis presenting with sinus disease in children. PMID- 8438800 TI - Brachydactyly secondary to pheochromocytoma. PMID- 8438801 TI - A steroid-responsive nephropathy in a child with human immunodeficiency virus infection. PMID- 8438803 TI - Life will never be the same. Violence in rural America. PMID- 8438802 TI - Cardiac injury from an air gun pellet: a case report. PMID- 8438804 TI - Heterogeneity and variability of inborn errors of metabolism. PMID- 8438805 TI - Late clinical presentation of partial carbamyl phosphate synthetase I deficiency. AB - OBJECTIVE: To describe the late manifestation of partial carbamyl phosphate synthetase I deficiency in an adolescent whose previous symptoms were not distinctive enough to suggest the presence of a metabolic disease. RESEARCH DESIGN: Clinical description of one patient. SETTING: Primary care children's hospital. PARTICIPANT: An adolescent boy. SELECTION PROCEDURE: Random observation. INTERVENTIONS: Intravenous sodium benzoate and sodium phenylacetate were more successful in reversing the coma than any other intervention. MEASUREMENTS/MAIN RESULTS: The patient has had no recurrence for 2 years, but he appears to have had a partial impairment of cognitive functioning. CONCLUSIONS: General pediatricians and intensivists should be aware that partial carbamyl phosphate synthetase I deficiency, and other partial urea cycle disorders, may become manifest in adolescence, even though they usually present in neonates or infants. When patients present in hyperammonemic coma, the urea cycle disorders should be considered, especially if no obvious cause is identified. PMID- 8438806 TI - Ketoconazole decreases the serum ionized calcium and 1,25-dihydroxyvitamin D levels in tuberculosis-associated hypercalcemia. AB - OBJECTIVE: To evaluate whether tuberculosis-associated hypercalcemia is related to abnormal synthesis of 1,25-dihydroxyvitamin D (1,25[OH]2D) and whether ketoconazole administration may be useful in treating tuberculosis-associated hypercalcemia. DESIGN: Case study. SETTING: Endocrine Unit, Pediatric Clinic, University of Pisa (Italy). PARTICIPANTS: Two boys (aged 10.5 years and 14.7 years) with active tuberculosis and hypercalcemia. MEASUREMENTS/MAIN RESULTS: At admission, serum 1,25-dihydroxyvitamin D levels were elevated. Oral ketoconazole administration (3.0 mg/kg every 8 hours) decreased 1,25-dihydroxyvitamin D levels within the first week of therapy (from 208.8 to 57.6 pmol/L [-72.4%] in one boy and from 321.6 to 115.2 pmol/L [-64.2%] in the other). We also found a coincident normalization of serum ionized calcium concentration (from 1.45 to 1.24 mmol/L [ 13.0%] in one boy and from 1.55 to 1.26 mmol/L [-17.0%] in the other). CONCLUSIONS: Abnormal elevated levels of 1,25-dihydroxyvitamin D caused hypercalcemia in our patients; ketoconazole administration may be effective in the treatment of hypercalcemia in patients with tuberculosis, which decreases 1,25-dihydroxyvitamin D synthesis. PMID- 8438807 TI - Plasma integrated concentration of growth hormone after recombinant human growth hormone injection. Implications for determining an optimal dose. AB - OBJECTIVE: To evaluate the effect of a standard dose of injected recombinant growth hormone on the integrated concentrations of growth hormone and insulin. DESIGN: Integrated concentrations were studied in patients receiving growth hormone therapy before and on the day of injection. SETTING: Pediatric endocrine clinic and diagnostic unit. PATIENTS: Twelve growth hormone-deficient patients with poor linear growth and deficient growth hormone response to provocative stimulation and/or 24-hour integrated concentration. INTERVENTION: Patients received subcutaneous injections of 0.06 mg/kg of growth hormone three times a week in the evenings at approximately 8 PM. Integrated concentrations were measured again approximately 6 months after the start of therapy at the time of a growth hormone injection. MEASUREMENTS AND RESULTS: Mean growth hormone dose administered was 2.0 +/- 0.5 mg. Integrated concentration of growth hormone was 2.2 +/- 0.9 micrograms/L before therapy. The integrated concentration of growth hormone after treatment (14.6 +/- 4.2 micrograms/L) was significantly higher than that before treatment and that of normally growing children (P < .001). After injection, peak growth hormone level was 53.7 +/- 24.1 micrograms/L; time to peak growth hormone level, 4.8 +/- 1.2 hours; constant of elimination, 0.24 +/- 0.06 per hour; half life, 3.0 +/- 0.7 hours; area under the curve, 328 +/- 85 (microgram.h)/L; clearance rate, 107.6 +/- 34.3 mL/min (3.2 +/- 0.8 mL/min per kilogram based on weight, 95.2 +/- 24.2 mL/min per meter squared based on surface area). There was no relationship between integrated concentration of growth hormone or pharmacokinetic variables after treatment and the growth response to 6 months' therapy. Integrated concentration of insulin before treatment was 19.0 +/ 10.9 mU/L, which was significantly lower than that after injection of growth hormone (33.4 +/- 9.5 mU/L; n = 9, P < .0008). CONCLUSIONS: Integrated concentrations of growth hormone after an injection of 0.06 mg/kg of growth hormone are considerably higher than spontaneous integrated concentrations of growth hormone observed in normally growing children, and associated with a rise in insulin secretion. These changes may be pertinent in patients with underlying insulin resistance or when higher doses of growth hormone are used for therapy. PMID- 8438808 TI - Health and social conditions of street children in Honduras. PMID- 8438809 TI - Insurance coverage and residents' experience in a pediatric teaching clinic. AB - To examine the relationship between insurance coverage and the diagnostic content of residents' experience in a hospital-based pediatric teaching clinic, we analyzed outpatient problem lists for 6543 patients seen in our clinic over a 15 month period. Problem-list contents were categorized using diagnostic clusters. The frequency distribution of clustered problems was compared for patients with four types of insurance coverage: indemnity insurance, health maintenance organization, Medicaid, and no insurance. The four insurance categories differed in the overall distribution of problems, but the differences could not be attributed to a disparity in the frequency of any single diagnosis or diagnostic cluster. We conclude that there was no important effect of insurance coverage on the diagnostic content of residents' experience in a teaching clinic. PMID- 8438810 TI - Comparison of the safety and immunogenicity of acellular (BIKEN) and whole-cell pertussis vaccines in 15- to 20-month-old children. AB - OBJECTIVE: To compare the immunogenicity and reactogenicity of a two-component acellular pertussis vaccine (BIKEN) with whole-cell diphtheria and tetanus toxoids and pertussis vaccine (WC-DTP) when administered to children aged 15 to 20 months. DESIGN: A randomized, double-blind study. SETTING: Children in this study were from 12 general pediatric practices (11 were private and one was university-affiliated) and one inner-city university pediatric clinic. PARTICIPANTS: Two hundred forty-six children aged 15 to 20 months who had received a three-dose primary series of standard WC-DTP vaccine during infancy. SELECTION PROCEDURES: Children were randomly assigned to receive either WC-DTP or one of three lots of acellular diphtheria and tetanus toxoids and pertussis vaccine (DT-aP) in a 1:3 ratio at the 11 private practices and in a 1:1 ratio at the university-affiliated practice and inner-city university pediatric clinic. INTERVENTIONS: The DT-aP vaccines contained 23.4 micrograms each of pertussis toxin and filamentous hemagglutinin per 0.5 mL and the same concentrations of diphtheria and tetanus toxoids as WC-DTP. Serum samples were obtained on the day of immunization and 4 to 6 weeks later. Adverse reactions at 6, 24, 48, and 72 hours were recorded by parents who were contacted by telephone at 24 and 72 hours and 14 days after immunization. MEASUREMENTS/MAIN RESULTS: An indirect enzyme linked immunosorbent assay method was used to determine IgG antibody response to pertussis toxin and filamentous hemagglutinin and IgG, IgA, and IgM to tetanus toxoids; a Chinese hamster ovary cell assay was used to measure functional antibodies to pertussis toxin; serum neutralization on VERO cells assayed diphtheria anti-toxin. Recipients of the DT-aP vaccine had fewer local reactions in the first 6 to 48 hours and fewer systemic reactions at 24 hours than did recipients of the WC-DTP vaccine. Acetaminophen was administered to 31% of DT-aP recipients compared with 63% of WC-DTP recipients. Infants given DT-aP had higher geometric mean antibody titer levels against pertussis antigens after vaccination. CONCLUSION: The BIKEN DT-aP vaccine used in this study is less reactogenic and more immunogenic for selected pertussis antigens than the WC-DTP vaccine in children aged 15 to 20 months. PMID- 8438811 TI - Comparison of a diphtheria and tetanus toxoids and bicomponent acellular pertussis vaccine with diphtheria and tetanus toxoids and whole-cell pertussis vaccine in infants. AB - OBJECTIVE: To compare the reactogenicity and immunogenicity of a diphtheria and tetanus toxoids and two-component acellular pertussis (ADTP) vaccine with a US licensed whole-cell (WDTP) vaccine. SETTING: General pediatric practice in suburban Rochester, NY. DESIGN: Prospective, double-blind, randomized study. PARTICIPANTS: One hundred ten infants were studied; 88 (80%) received ADTP and 22 (20%) received WDTP at ages 2, 4, and 6 months. INTERVENTION: Vaccination. MEASUREMENTS/MAIN RESULTS: Temperature of 38.3 degrees C or higher (P = .03) and moderate or severe injection-site pain (P = .02) occurred less frequently in infants receiving ADTP than those receiving WDTP for the combined three doses. Following the third dose, ADTP vaccination produced higher antibody responses than WDTP to pertussis toxin (geometric mean enzyme-linked immunosorbent assay IgG was 52.2 vs 12.5; P < .001) and to filamentous hemagglutinin (geometric mean IgG was 182.8 vs 3.5; P < .001). No interference in the diphtheria or tetanus antibody responses was observed in recipients of the ADTP vaccine. CONCLUSIONS: This two-component ADTP vaccine, when given as a primary infant series, produces fewer adverse effects and greater immunogenicity to the two pertussis components that it contains than US-licensed WDTP vaccine. PMID- 8438812 TI - Q fever in children. AB - OBJECTIVE: To describe clinical profiles of Q fever in children. DESIGN: Retrospective study. SETTING: Tertiary teaching hospital. PARTICIPANTS: Thirteen children aged 2 to 14 years, with a mean +/- SD age of 9.6 +/- 3.6 years. SELECTION PROCEDURES: Review of the medical records of all children with Q fever admitted from 1986 to 1990. The diagnosis was made by detection of phase II antibodies to Coxiella burnetii by the complement fixation test. MEASUREMENTS/MAIN RESULTS: Clinical profiles consisted of a self-limited illness characterized by high fever (mean +/- SD, 39.9 degrees C +/- 0.66 degrees C) of 5 to 10 days' duration (mean +/- SD, 7.4 +/- 1.6 days), constitutional symptoms, and mild liver dysfunction. Eleven patients had gastrointestinal manifestations (vomiting and/or abdominal pain). Respiratory symptoms were not prominent. Most patients had normal or low white blood cell counts, and seven showed a relative increase of band forms. Their erythrocyte sedimentation rates ranged from 8 to 23 mm/h. All patients did well without specific therapy for C burnetii. CONCLUSION: In children with the symptoms described above, tests to detect antibodies to C burnetii should be performed. PMID- 8438813 TI - Preterm twins and triplets. A high-risk group for severe respiratory syncytial virus infection. AB - OBJECTIVE: To assess the impact of multiple births and crowded homes on the severity of respiratory syncytial virus illness in preterm infants with bronchopulmonary dysplasia. RESEARCH DESIGN: Retrospective case-control chart review from a prospective longitudinal respiratory illness study. SETTING: Neonatal High-Risk Follow-Up Clinic (outpatient setting) and tertiary care hospitals (inpatient setting). PARTICIPANTS: Fourteen sets of twins and two sets of triplets followed up between 1983 and 1989 and matched with 34 singleton infants for date of birth (within 3 months) and gestational age (within 1 month). MEASUREMENTS/MAIN RESULTS: The risk of developing respiratory syncytial virus illness was significantly higher in multiple-birth infants than in singletons (53% vs 24%; P = .01). Multiple-birth infants were also at greater risk for developing pneumonia (24% vs 6%; P = .05) and requiring hospitalization (32% vs 18%; P = .05) than were singletons. Additional risk factors for developing pneumonia and bronchiolitis were examined in all 68 children. Multiple birth (P = .05), gestational age of less than 30 weeks (P = .02), and crowded homes (defined as more than one person living in 19 m2 of living space [P = .002] or more than one child living in 22 m2 of living space [P = .004]) were additional risk factors for developing pneumonia. CONCLUSION: Multiple-birth preterm infants are at a higher risk of developing pneumonia than are singletons. Additional risk factors for developing pneumonia in preterm infants with bronchopulmonary dysplasia include gestational age of less than 30 weeks and crowded homes. At risk infants with any of these risk factors should be targeted for prophylactic and therapeutic interventions against respiratory syncytial virus. PMID- 8438814 TI - Radiological case of the month. Congenital pyloric atresia in Down syndrome. PMID- 8438815 TI - Radiological case of the month. Foreign-body aspiration. PMID- 8438816 TI - Picture of the month. Phytophotodermatitis. PMID- 8438817 TI - Picture of the month. Infantile Marfan syndrome. PMID- 8438818 TI - Pathological case of the month. Helicobacter pylori gastritis. PMID- 8438819 TI - Pathological case of the month. Thoracic and abdominal actinomycosis. PMID- 8438820 TI - Acquired ocular visual impairment in children. 1960-1989. AB - OBJECTIVE: To describe the causes, sites, and types of eye anomaly and associated handicaps in children identified in the last 30 years with ocular visual impairment of 20/200 (6/60) or worse in the better eye with correction. DESIGN: Trend study. STUDY POPULATION: Children in British Columbia younger than 19 years with visual loss diagnosed between January 1960 and December 1989 who were referred for multidisciplinary assessment. RESULTS: The incidence of acquired ocular visual impairment has decreased from 0.6 to less than 0.2 per 10,000 people aged 19 years or younger during the last 30 years. The most common cause was a genetic cause, followed by tumor, injury, infection and autoimmune disorders. Optic nerve atrophy and retinal disorders together resulted in more than 90% of all ocular lesions. Gender distribution revealed more males than females to be affected. Sixty-six percent of children had enough sight to read. The percentage of affected children with neurologic disabilities has increased overall in the last 30 years because more children with profound brain damage have survived. CONCLUSIONS: Acquired ocular visual impairment is rare. The incidence of such impairment has been reduced by two thirds in the last 30 years. This decline has had little impact, however, because most cases of blindness are due to congenital conditions. The number of cases of acquired blindness is only one fourth that of congenital blindness, which has begun to increase again owing to the reemergence of retinopathy of prematurity. PMID- 8438821 TI - Survival of profoundly disabled people with severe mental retardation. AB - OBJECTIVE: To define further the association between survival and clinical disabilities in profoundly disabled people with mental retardation in an 11-year period. RESEARCH DESIGN: An 11-year follow-up study of the survival of six mutually exclusive subgroups. The presence of severe, profound, or suspected mental retardation and incontinence were considered in all individuals when forming the subgroups. Varying combinations of abilities in mobility, rolling, feeding, and arm-hand use were also considered. PARTICIPANTS: Six subgroups of severely disabled subjects. Included were 128,248 of 155,851 persons who received services from the California Department of Developmental Services between January 1980 and March 1991. MEASUREMENTS/MAIN RESULTS: Survival estimates for individuals who were immobile and could not roll over were short regardless of arm-hand use or feeding status, as were estimates for people who were tube fed. For individuals who could roll over, but were otherwise immobile, survival was relatively improved. CONCLUSION: Individuals who are unable to move their extremities or bodies voluntarily or who require tube feeding have very shortened life expectancies. PMID- 8438822 TI - Are children born small for gestational age at increased risk of short stature? AB - OBJECTIVE: To assess the height outcome of newborns born small for gestational age. DESIGN: A historical prospective study. SETTING: A cohort of 1758 newborns born at a single university hospital maternity ward and subsequently examined at the military draft medical board at age 17 years. PARTICIPANTS: Newborns whose weight at birth was below the third percentile were defined as small for gestational age. Their body measurements at age 17 years were compared with those of their peers who were appropriate for gestational age. MEASUREMENTS/MAIN RESULTS: The adjusted mean +/- SEM height for boys born small for gestational age vs peers born appropriate for gestational age was 169.9 +/- 1.5 vs 175.4 +/- 0.8 cm (P < .0001); and for girls, 159.4 +/- 1.3 vs 163.1 +/- 0.8 cm (P < .0005). In addition, the risk for height attainment below the 10th percentile was significantly increased for newborns born small for gestational age. The adjusted odds ratio was 4.13 for boys (95% confidence interval, 1.66 to 10.25; P < .0006) and 3.32 for girls (95% confidence interval, 1.38 to 8.05; P < .0005). CONCLUSION: Infants born small for gestational age may be at increased risk for short stature in late adolescence. PMID- 8438823 TI - A quality assurance program for the measurement of capillary blood cholesterol levels in private pediatric practices. The Children's Health Project. AB - OBJECTIVE: To develop an easy to use quality assurance program for the measurement of capillary blood cholesterol levels in private pediatric practices. The program needed to comply with the guidelines laid down by the National Cholesterol Education Program. DESIGN: Intervention study. SETTING: Nine private pediatric practices in and around northern Philadelphia, Pa. PARTICIPANTS: The analysts included clinic staff members with laboratory expertise ranging from none to some previous experience. None of the participants had previous experience with a quality assurance program. INTERVENTIONS: Progress was reported monthly to the Lipid Research Laboratory, Philadelphia, and action was taken to correct inaccuracies in bias or variance. MAIN OUTCOME MEASURE: Compliance with the analytical guidelines laid down by the National Cholesterol Education Program in that the coefficient of variation was no greater than 5% and the bias was no greater than +/- 5% in the first year of the study. RESULTS: Within the first year of the study, there were 152 monthly quality assurance returns for each of two lyophilized control materials. On four occasions the coefficient of variation was greater than 5% while the overall bias was within the desired +/- 5% on 143 (94%) of 152 occasions. After the first 3 months of the study, as user confidence increased, intervention by the Lipid Research Laboratory became minimal. The internal quality assurance was further evaluated by a successful performance in a quarterly external quality assurance program. CONCLUSIONS: It is possible to devise an easy to use quality assurance program for extra laboratory measurement of cholesterol levels in children, and, with minimal assistance, maintain acceptable standards of cholesterol analysis. The quality assurance improved following the first 3 months of training and education. Subsequent continuous quality improvement was maintained with minimal involvement of the specialist center. Should the controversial issue of private office measurement of blood cholesterol levels become universally acceptable, the implication from our study is that standards acceptable to the National Cholesterol Education Program and the Clinical Laboratory Improvement Amendments of 1988 are possible using a suitable quality assurance program. PMID- 8438824 TI - A comparative study of heel-stick devices for infant blood collection. AB - OBJECTIVE: To evaluate two heel-stick devices by comparing the volume of blood collected, blood sampling time, amount of hemolysis, pain inflicted during the procedure, and extent of bruising. DESIGN: Randomized trial. SETTING: Primary care center in a tertiary-level perinatal hospital. PARTICIPANTS: Forty healthy, full-term newborns with a postnatal age of greater than 24 hours. Newborns were fed no more than 1 1/2 hours before blood sample collection and fulfilled the requirement for routine phenylketonuria and thyroid screening. INTERVENTIONS: Newborns were allocated to a single stab with either an automated incision or a lancet puncture device. MEASUREMENTS/MAIN RESULTS: The total volume of blood and blood sampling time were significantly better with the automated incision device (P < .001). Hemolysis was also reduced with the automated incision device (P < .03). Plasma hemoglobin levels were below 1.0 g/L in all samples obtained with the automated incision device and in 71% of samples obtained with the lancet device. There were no differences in the extent of bruising or in pain symptoms manifested by mean increases in heart rate and percentage of time crying during the procedure. CONCLUSIONS: The larger volume of blood obtained within a shorter period for blood collection and reduced hemolysis with the automated incision device make it a preferred instrument for neonatal blood collection. PMID- 8438825 TI - The effects of skills and intentions to use drugs on posttreatment drug use of adolescents. AB - The present study examines the relationship between (a) social, cognitive, and behavioral skills; (b) self-reported intentions to use drugs and alcohol following treatment; and (c) later drug and alcohol use for a sample of 130 adolescents. Social, problem solving, self-control, and drug and alcohol avoidance skills were significantly related to marijuana use, variety and severity of drug use, and to the number of drug-free months for female subjects at 12-month follow-up. These skills did not have a statistically significant direct effect on any measured drug outcomes for males. However, skills did lower male subjects' intentions to use drugs or alcohol. Decreased intentions to use, in turn, were associated with less drug and alcohol use, suggesting an indirect relationship between skills and reductions in drug and alcohol use among males at 12-month follow-up. Implications for the treatment of adolescents who engage in drug and alcohol use are discussed. PMID- 8438826 TI - Correlates of drug injection behaviors among methadone outpatients. AB - Intravenous drug use, which has been recognized as the second most common risk behavior associated with AIDS, was studied among methadone outpatients who were enrolled in a methadone program at a hospital-based clinic in New York City. Intercorrelations among the following variables were observed: sociodemographic, psychological, drug use patterns, and criminal history. Then a stepwise discriminant analysis was employed to examine factors differentiating the high risk clients from the lower risk clients in terms of needle use/sharing in the 30 days prior to the interview. The subjects (N = 152) were heterosexual (95%), non White (63%), had no more than 12 years of education (72%), were not full-time employed (65%), and had been arrested at least once (79%). The median age at the time of entering the methadone treatment was 33 and the median length of stay in the treatment was 17.5 months (mean = 44.7 months), with an average 52 mg of methadone dosage. Results indicated that risk behavior in terms of current needle use/sharing occurred in about 16% of a sample of clients in the methadone maintenance. A shorter length of stay in treatment was the strongest predictor of high risk, followed by early arrest history, ethnicity, depression, and employment status. PMID- 8438827 TI - The role of work for wives of alcoholics. AB - The family has increasingly been recognized as an important component in the development, maintenance, and treatment of alcoholism. Few empirical studies, however, have examined alcoholism within a family context. Questionnaire and interview data were collected from women whose husbands received inpatient treatment for alcoholism. Since wives now typically work outside the home, this article focuses on the 60 employed wives. Employment was examined as a source of stress as well as social support. The majority of working wives reported minimal negative impact of their husbands' drinking on all areas of their work functioning, with a small subset indicating impairment attributable to the drinking. These wives were very satisfied with their current positions and described work as a positive experience. However, unobtrusive measures that alcoholism in a family member intrudes into the workplace were apparent, including changing jobs, absenteeism, and discussing husbands' drinking at work. Further, these women scored closer to a sample of depressed women than a community sample on measures of physical and mental health, depressed mood, and smoking symptoms. Possible reasons for the discrepancy between subjective reports and objective indicators are discussed. PMID- 8438828 TI - Meprobamate dependence secondary to carisoprodol (Soma) use. PMID- 8438829 TI - Sexual versus psychiatric predictors of suicide in men with AIDS-related illnesses. PMID- 8438830 TI - Implementation issues and techniques in randomized trials of outpatient psychosocial treatments for drug abusers. II. Clinical and administrative issues. AB - This paper focuses on implementation problems in randomized trials of outpatient psychosocial treatments for drug abusers. The authors examined these problems in nine clinical trial studies and drew on published literature and their own research experiences. Common problems faced by principal investigators include the need for midstream treatment protocol and research design modifications based on the response of both clients and clinical staff, tension between research and clinical requirements, and the need to administer a large, complex organization over a substantial period of time. Solutions include conducting a pilot study, employing advanced research and analysis methods that can incorporate complex design variations, fostering a team spirit between diverse staffs, and employing special management structures. PMID- 8438831 TI - A psychotherapeutic approach to substance abuse: preliminary observations. AB - Twenty-four long-term substance abusers were told that addiction is an attempt to adapt to an insufficiency in natural neurochemicals that contribute to a sense of well-being; this insufficiency is experienced as a craving for abuse substances which mimic the missing anxiolytic and euphorigenic neurochemicals. They were also told that they could satisfy their cravings immediately and completely without taking abuse substances by intentionally restoring adequate levels of the depleted neurochemicals. To perform this self-regulation, they were taught a specific psychological technique that united reason and emotion in an unambivalent order to the brain. Nineteen abusers (79%) were able to use the procedure to relieve all substance cravings and withdrawal symptoms. Their remissions have lasted 41 to 66 months to date (July 1991). A replication of the findings reinforces the desirability of further studies of the treatment's effectiveness and mechanisms. PMID- 8438832 TI - Exposure to methadone programs and heroin use. AB - The aims of this study were to: (a) assess the effects of various patterns of exposure to methadone programs on heroin use; (b) assess the effects of other patient, program, and treatment variables; and (c) identify variables that promote the type of exposure to methadone programs that is most effective for reducing heroin use. The sample was 526 patients who were admitted from 1979 to 1981 into 17 methadone programs that participated in the Treatment Outcome Prospective Study. The study differs from previous research in that it addresses the time that patients spent in methadone programs during the follow-up period in defining exposure patterns. Heroin use was lowest among patients who were continuously exposed to methadone programs. Retention was highest among patients who attended programs that informed them of their methadone dose levels, were easy to access, and provided them with high quality social services. PMID- 8438833 TI - Three-month follow-up of 28 dual diagnosis inpatients. AB - The coexistence of psychiatric and substance abuse problems within the same patient occurs with significant frequency. These patients present serious challenges to a health care system which has traditionally treated mental health and substance abuse in separate venues, with differing and sometimes contradictory treatment modalities. Few studies exist on the treatment of the "dual diagnosis" patient utilizing an integrated approach, where both problems are addressed by the same staff on a single inpatient ward. We describe such a program in which dual diagnosis patients on one ward are separated into two different treatment tracks based upon the severity of their psychiatric illness. Follow-up measures at 3 months after discharge are compared for patients from each treatment track, with no significant difference found for the five outcome variables studied. This suggests that chronically mentally ill inpatients may benefit from integration of attention to their substance abuse problems with psychiatric treatment. PMID- 8438834 TI - Treatment effectiveness for legally coerced versus voluntary methadone maintenance clients. AB - Analyses examined whether addicts reporting themselves coerced into drug abuse treatment by actions of the criminal justice system differed from voluntary admissions in their response to treatment, and whether such responsiveness varied across gender or ethnicity. Six hundred eighteen methadone maintenance clients admitted to programs in six southern California counties were categorized into high, moderate, and low legal coercion levels. Multivariate analysis of variance procedures for repeated measures (before, during, and after initial treatment episode) were used to test relevant hypotheses. Dependent variables included criminal justice system contact, criminal activities, drug and alcohol involvement, and measures of social functioning. Few differences within any measured domain were found among the three groups. All groups were similar in showing substantial improvement in levels of narcotics use, criminal activities, and most other behaviors during treatment with some regression in these behaviors posttreatment. Results support legal coercion as a valid motivation for treatment entry; those coerced into treatment respond in ways similar to voluntary admissions regardless of gender or ethnicity. PMID- 8438835 TI - A question of quality. PMID- 8438836 TI - Laparoscopic cholecystectomy for acute cholecystitis. PMID- 8438837 TI - Laparoscopic cholecystectomy: the procedure of choice for acute cholecystitis. PMID- 8438838 TI - The safety and clinical utility of esophagogastroduodenoscopy for acute gastrointestinal bleeding after myocardial infarction: a six-year study of 42 endoscopies in 34 consecutive patients at two university teaching hospitals. AB - The risks versus benefits of panendoscopy performed soon after myocardial infarction were studied. At Robert Wood Johnson University Hospital from January 1986 through December 1991 and at Princeton Medical Center from January 1990 through December 1991, 82 patients developed overt gastrointestinal bleeding (1.2% of all myocardial infarctions) and 14 patients developed occult gastrointestinal bleeding (0.2% of all myocardial infarctions) within 3 weeks after myocardial infarction. Thirty-four of the patients underwent 42 panendoscopies within 3 weeks of myocardial infarction. Indications for the initial endoscopy included hematemesis in 25, melena without hematemesis in four, red blood per rectum in three, and occult blood in the stool in two. The initial panendoscopy, on average, was performed 6.2 +/- 7.5 (SD) days after myocardial infarction. The 34 initial panendoscopies provided the diagnosis in 27 (79%), and clinically helpful information in four (12%). Common diagnoses were duodenal ulcer in 11, hemorrhagic gastritis in four, and hemorrhagic esophagitis in three. Three complications were due to the initial endoscopy, including fatal ventricular tachycardia, near respiratory arrest, and hypotension. These complications occurred in three (37.5%) of eight patients who were significantly unstable before endoscopy. No (0%) complications occurred in the 26 relatively clinically stable patients undergoing the initial endoscopy. This difference in complication rate was statistically significant (p < 0.01, Fisher's exact test). We conclude that recent myocardial infarction is not an absolute contraindication to panendoscopy. In this retrospective study, the benefits exceeded the risks of panendoscopy in medically stable patients with significant gastrointestinal bleeding. Panendoscopy should be performed with monitoring by electrocardiography and pulse oximetry after stabilization of vital signs, which may require transfusion of blood products, supplemental oxygen administration, endotracheal intubation, and mechanically assisted ventilation. Panendoscopy in highly unstable patients had a high complication rate in this study. PMID- 8438839 TI - A comparison of esophageal motility in response to bread swallows and water swallows. AB - Studies of esophageal manometry during eating have demonstrated abnormal motility in patients with dysphagia in whom standard water-swallow manometry was normal. However, there have been few concurrent motility studies making a direct comparison of food swallows with water swallows. This paper presents the results of such a study in 20 healthy volunteers. A comparison of bread swallows with water swallows revealed that both peristaltic amplitude in the proximal esophagus and peristaltic duration throughout the esophagus were significantly increased (p < 0.05). Peristaltic propagation velocity was significantly decreased in the proximal and mid-esophagus (p < 0.05). Percentages of nonconducted and nonperistaltic contractions were significantly increased (p < 0.05-0.001) during bread-swallow manometry. Therefore, the response of the normal esophagus to food has been shown to be different from its response to water swallows. In particular, the high percentage of nonpropagated swallows in normal subjects when eating indicates that the results of food manometry in patients with dysphagia must include wider limits of normality. PMID- 8438840 TI - Passive smoking is associated with an increased risk of developing inflammatory bowel disease in children. AB - Adult cigarette smoking is associated with the development of Crohn's disease and protection from the development of ulcerative colitis. Children usually are nonsmokers whose risk of developing inflammatory bowel disease (IBD) may be related to passive smoking. The purpose of this matched case-control study was to evaluate passive smoking exposure in 72 nonsmoking children with recently diagnosed IBD (39 with ulcerative colitis and 33 with Crohn's disease), and in an equal number of peer-nominated controls. Passive smoking exposure at birth was significantly associated with the development of IBD (odds ratio 3.02, 95% confidence interval 1.28-7.06). The effect was greater in Crohn's disease (odds ratio 5.32) than in ulcerative colitis (odds ratio 2.19). Maternal smoking at birth also was significantly associated with the development of IBD (odds ratio 2.09, 95% confidence interval 1.02-4.29), an effect that also was greater in Crohn's disease than in ulcerative colitis. There was a dose-response relationship between packs smoked per day and IBD, and packs smoked at home per day and IBD. At symptom onset, the risk of developing IBD from passive smoking exposure was increased but was not significant (odds ratio 1.88, 95% confidence interval 0.84-4.18). The magnitude of the effect was greater in Crohn's disease than in ulcerative colitis, and the association demonstrated dose-response. In conclusion, passive smoking exposure and maternal smoking at birth and, to a lesser extent, passive smoking exposure at symptom onset are associated with an increased risk of developing IBD in children. The association is stronger in Crohn's disease than in ulcerative colitis, and there is a dose-response effect. The specific toxic exposure is more likely to be inhaled rather than passed through the placenta or in breast milk. PMID- 8438841 TI - Relationship between Helicobacter pylori colonization and acute inflammation of the duodenal mucosa. AB - A relationship between Helicobacter pylori colonization and acute inflammation of the duodenal mucosa was studied in 75 patients with duodenal ulcer and nine with endoscopically normal duodenal mucosa. A biopsy of the duodenal bulb in each patient was used for both detection of H. pylori and histological assessment of acute inflammation [polymorphonuclear leukocyte (PMN) infiltration and regenerative changes of the duodenal epithelial cells]. Biopsies with regenerative changes showed a marked PMN infiltration, regardless of the duodenal H. pylori status. In biopsies without regenerative changes, H. pylori colonization was closely associated with PMN infiltration. Acute inflammation in the duodenal mucosa surrounding ulcers is caused mainly by acid, but our data suggest that H. pylori is another important factor in the development of PMN infiltration in the duodenal mucosa. PMID- 8438842 TI - Gastrointestinal motility in patients with non-ulcer dyspepsia: a role for Helicobacter pylori infection? AB - Motor disorders of the upper gastrointestinal tract are a frequent finding in patients with non-ulcer dyspepsia (NUD). In this study we attempted to assess whether Helicobacter pylori infection contributes to gastrointestinal motor disorders in NUD. Interdigestive and post-prandial gastrointestinal motility was studied in 46 consecutive patients with NUD and in eight healthy control subjects. Abdominal complaints were assessed by means of a symptom score. Chronic gastritis and H. pylori infection were assessed and graded by histology. Accordingly, patients with NUD were divided into two sub-groups: 18 patients with H. pylori infection and chronic active gastritis and 28 patients without H. pylori infection. The length of the interdigestive motor cycle was not different in patients with NUD (139 +/- 6 min, mean +/- SEM), compared with controls (128 +/- 5.5 min). There was also no difference in the duration of individual phases I, II, and III, either between NUD and controls or between H. pylori-positive and -negative patients. The motility index (MI) of antral phase II also was not changed in NUD patients. Postprandial antral motility was decreased in patients with NUD (MI 6.96 +/- 0.4 vs. 9.7 +/- 0.3 controls; p < 0.025), with no difference between H. pylori-positive and -negative subgroups. It therefore appears unlikely that H. pylori infection plays a primary role in the pathophysiology of antroduodenal motor disorders in NUD. PMID- 8438843 TI - Collagenous colitis: are bacterial cytotoxins responsible? AB - In a case of collagenous colitis, cholestyramine treatment resulted in symptomatic and histological normalization. After discontinuation of cholestyramine, collagenous colitis relapsed. At this time fecal cytotoxic activity was demonstrated in McCoy cell lines. Symptoms, histologic changes, and cytotoxicity disappeared when cholestyramine treatment was reinstituted. We hypothesize that a bacterial toxin is responsible for the development of collagenous colitis. PMID- 8438844 TI - Esophageal motor function in primary Sjogren's syndrome. AB - To evaluate esophageal motor function in patients with primary Sjogren's syndrome (PSS) and its relation to the presence of dysphagia, 20 outpatients, who met the four criteria for PSS proposed by Fox et al. were prospectively studied by esophageal manometry after dry or wet swallows. Dysphagia was present in 15 (75%) patients, although the presence or severity of the symptom was not related to any specific motility pattern. Moreover, this study did not show any correlation between dysphagia and degree of inflammatory infiltrate of the labial minor glands, the parotid flow rate, or the presence of autoantibodies. In conclusion, although dysphagia is a common complaint in patients with PSS, esophageal motor studies have failed to show any consistent pattern. PMID- 8438845 TI - Routine tests of renal function, alcoholism, and nutrition improve the prognostic accuracy of Child-Pugh score in nonbleeding advanced cirrhotics. AB - In an attempt to improve the prognostic capacity of Child-Pugh score in nonbleeding cirrhotics, 110 consecutive in-patients without gastrointestinal hemorrhage at admission were studied and followed up for 24 months or until death. Fifty-five of the 110 patients (50%) died during this period. Mean survival time was 18.8 +/- 1.4 months (mean +/- SEM). In addition to Child-Pugh score, eight variables, including anthropometric nutritional parameters, routine renal function tests, and alcoholism markers, were recorded at admission. The ability of these variables to improve the prognostic capacity of the Child-Pugh score was assessed with the proportional hazard Cox's regression procedure, using a stepwise method for covariate selection, after including the Child-Pugh score at the first step. Thus, in addition to Child-Pugh score (beta = 0.302), three variables were included in the final model: serum urea (beta = 0.113), MCV (beta = 0.027), and mid-arm muscle circumference (beta = -0.025). According to the contribution of each of these factors to the model, a prognostic index was obtained to estimate survival in the individual patient. An assessment of the predictive power of the model was made by means of a split-sample technique. The prognostic index described in this study may contribute to improve the selection of nonbleeding patients with advanced cirrhosis to receive specific therapies such as transplantation. However, its true clinical relevance will be established only by prospectively comparing its prognostic value with that of the Child-Pugh score in a new sample of patients. PMID- 8438846 TI - Short-term prognosis of cirrhotics with spontaneous bacterial peritonitis: multivariate study. AB - In order to identify the predictive factors of hospital mortality in cirrhotics with spontaneous bacterial peritonitis (SBP), we studied 64 patients who fulfilled the accepted diagnostic criteria. All cases were treated with cefotaxime up to 2 days after the infection was considered cured (7.7 +/- 2.9 days). Eleven patients (17%) died while in hospital, six of them before SBP was cured. After uni- and multivariate analyses, only seven routine clinical, biological, and bacteriological variables studied were independently associated with hospital mortality. These were: the presence of upper gastrointestinal bleeding at admission (beta = 2.01), the absence of abdominal pain as presenting symptom (beta = -1.29), the polymorphonuclear count (%) in the ascites (beta = 0.48), prothrombin rate (beta = -0.22), and serum Na (beta = -0.64), creatinine (beta = 0.50), and cholesterol (beta = -0.68). When the equation obtained was computed in a randomly selected sample of the patients studied, it correctly predicted the outcome in 92.3% of the cases. We conclude that short-term outcome of SBP patients depends on the existence of recent gastrointestinal bleeding, the severity of SBP, and the degree of liver and renal failure. The prognostic value of this model needs prospective validation in a new series of patients. PMID- 8438847 TI - Treatment of duodenal ulcer with omeprazole or ranitidine in a Brazilian population: a multicenter double-blind, parallel group study. AB - Two hundred and forty-one patients with at least one ulcer at stage A1 or A2, measuring at least 5 mm in its larger diameter, were included in this Brazilian double-blind randomized study. Patients received omeprazole 20 mg in the morning (n = 120) or ranitidine 300 mg at night (n = 121) for 2 wk; unhealed ulcers were treated for an additional 2 wk. At the end of 4 wk, unhealed ulcers were treated openly with omeprazole 20 mg o.m. for 4 wk. Healing rates at 2 and 4 wk were 67.3% and 92.9% for omeprazole and 39.8% and 82.0% for ranitidine (per protocol analysis). Results were similar when analyzed as intention to treat (p significant in favor of omeprazole). Epigastric day-time pain was the most common of all symptoms (89.2%), but only heartburn at day 15 showed a significantly better response to omeprazole than to ranitidine. A multivariate analysis (logit analysis) showed that the odds in favor of healing were greater for small ulcers, nonsmokers, and omeprazole treatment. PMID- 8438848 TI - Increased expression of epidermal growth factor receptors in Barrett's esophagus associated with alkaline reflux: a putative model for carcinogenesis. AB - A 49-yr-old male was reviewed who had a 10-yr history of reflux esophagitis. He presented initially with frequent heartburn of moderate severity and, on subsequent endoscopy, was noted to have erosive esophagitis and, at that time, a high maximal gastric acid output. During the next 5 yr, his symptoms and acid output diminished. Eight years after presentation, he was noted to have developed a small area of Barrett's metaplasia, without dysplastic change. Ten years after the initial presentation he was completely asymptomatic, despite having extensive Barrett's metaplasia, now with high grade dysplasia. As a result, he was referred for esophagogastrectomy. At the time of surgery, he had alkaline reflux, with antacid gastric contents and, subsequently, hypochlorhydria was proven by a pentagastrin test. A second individual (male, 46 yr) who presented initially with reflux symptoms and gastric-type metaplasia, underwent gastric secretory studies that revealed a peak acid output of 16 mmol/L in 1986. During the period 1989 to 1991, his symptoms progressed despite H2 antagonist therapy. In this regard he was reinvestigated, and his peak acid output in 1991 was 0 mmol/L, and subsequent esophageal biopsies demonstrated intestinal metaplasia in four of six biopsies (two biopsies had high-grade dysplasia; the two others had gastric-type metaplasia). He has refused esophageal resection, and is being reviewed regularly at the endoscopy clinic. Flow cytometric analysis of the esophagus in both individuals revealed expression of epidermal growth factor receptor which was increased in the areas of high grade dysplasia, compared with Barrett's mucosa without dysplasia or normal cardiac mucosa. We conclude that alkaline reflux may accelerate the development of Barrett's esophagus (and intestinal type metaplasia) in patients with gastroesophageal reflux disease. The increased expressed of epidermal growth factor receptors in Barrett's mucosa with dysplasia compared with Barrett's mucosa without dysplasia may reflect the higher malignant potential of the former mucosa. PMID- 8438849 TI - Serum levels of CA 50 in nonmalignant liver diseases: a clinical and biochemical study. AB - CA 50 is a tumor marker used in the evaluation and follow-up of some cancers, especially of the digestive tract. However, CA 50 frequently produces false positive results, particularly in pancreatic and hepatobiliary diseases. This study was carried out to evaluate the behavior of CA 50 in 159 patients with benign diffuse liver diseases, who underwent a thorough clinical and laboratory evaluation. There were abnormal levels of CA 50 in 56% of the 159 patients, and in 75.3% of the 85 cirrhotics, with very high values in some cases. We found significant correlations between CA 50 and some clinical and biochemical parameters. Significantly higher levels of CA 50 were found in cirrhotics than in noncirrhotics (p < 0.0001), and in hyperbilirubinemic patients than in those with normal bilirubin (p < 0.0001). Several mechanisms, including liver dysfunction and pathological changes of the smallest bile ducts, probably are responsible for the increase in CA 50. Several cut-offs for different subsets of patients, according to the diagnosis and level of bilirubin, have been calculated. Whenever CA 50 is used in the evaluation of a cancer patient, a benign liver disease should be excluded, because the liver disorder can result in increased serum levels of CA 50, independent of cancer. PMID- 8438850 TI - B-cell clonal detection in gastric low-grade lymphomas and regional lymph nodes: an immunohistologic and molecular study. AB - Gastric low-grade B cell lymphomas originating in mucosa-associated lymphoid tissues are composed of reactive hyperplastic germinal centers and interfollicular centrocyte-like cells. Their polymorphic, histologic composition and infrequent dissemination beyond the gastric wall led to the denomination of these tumors as "pseudolymphomas." To elucidate their clonal character, a Southern blot study of DNA and immunohistological study was carried out on 14 cases of surgical specimens from gastrectomy (11 low-grade and three high-grade tumors). Monoclonal and polyclonal antibodies were used on frozen and paraffin sections. A mucosa-associated lymphoid tissue origin for the tumors was assigned due to their centrocyte-like morphology and the presence of lymphoepithelial lesions. Southern blot analysis of DNA and immunohistological results confirm the monoclonal composition of gastric low-grade lymphomas in all cases. Although both types of technique correlated well on the predominant light-chain, Southern blot DNA study was nevertheless more sensitive than the immunohistochemical techniques. Surprisingly, in two cases of gastric low-grade lymphoma, Southern blot DNA analysis of histologically reactive regional lymph nodes showed an unexpected immunoglobulin heavy chain gene rearrangement. This coincided with that found in the gastric wall. Results confirm the monoclonal nature of the low grade gastric lymphoma. This supports consideration of this tumor as an indolent primary lymphoma of the stomach, confirming the suitability of excluding the term "pseudolymphoma." Involvement of regional lymph nodes may be a more frequent occurrence than previously detected through morphological study. PMID- 8438851 TI - Rhabdomyolysis associated with the use of intravenous vasopressin. AB - A patient with acute esophageal variceal bleeding developed fatal rhabdomyolysis during treatment with a continuous intravenous infusion of vasopressin. Signs of ischemia, including mottling of skin and painful extremities, preceded the development of the characteristic electrolyte abnormalities and cardiac arrhythmias. No other recognized causes of rhabdomyolysis were identified on retrospective review of the hospital course. There are several factors which might promote a peripheral ischemic response to vasopressin in the bleeding cirrhotic patient, including altered resting hemodynamics, increased resting sympathetic tone, impaired vasodilation as a compensatory response to vasopressin, and reduced hepatic drug clearance. Idiosyncratic factors involving vasopressin receptor affinity and distribution, vasopressin-associated vasodilation in some vascular beds, and the effect of vasopressin on the renin angiotensin system may further contribute to impaired tissue perfusion. These multiple overlapping factors probably lead to rhabdomyolysis in a minority of patients receiving vasopressin infusion. PMID- 8438852 TI - Flexible video vaginoscopy and its use in enterovaginal fistulas. AB - The demonstration of the pathway of enterovaginal fistulas has been challenging physicians since first described. This case demonstrates a new method for elucidating the tract pathway via flexible vaginoscopy, the use of catheters for endoscopic retrograde cholangiopancreatography, and plain films of the pelvis. PMID- 8438853 TI - Hepatic coma as a presenting feature of constrictive pericarditis. PMID- 8438854 TI - Diffuse nodular regenerative hyperplasia of the liver associated with human immunodeficiency virus and visceral leishmaniasis. AB - We present a patient with human immunodeficiency virus (HIV) infection coincident with diffuse nodular regenerative hyperplasia (DNRH) of the liver and visceral leishmaniasis. This association has not been previously described. Some DNRH cases are secondary to irregular blood flow in the liver. In the presently described case, there exist two possible conditioning factors for heterogeneous distribution of blood flow: 1) the increased blood flow from splenomegaly, and 2) the irregular circulation of blood through sinusoids infiltrated by Leishmania parasitized hyperplastic macrophages. PMID- 8438855 TI - Angioedema presenting as chronic gastrointestinal symptoms. AB - Gastrointestinal complaints may be the presenting feature of patients with acquired or hereditary angioedema. We describe two patients with episodic nausea, abdominal pain, and cramping secondary to C1 inhibitor deficiency. In one patient, an acquired deficiency arose as a paraneoplastic syndrome with abdominal complaints preceding the diagnosis of an occult lymphoma. The second patient presented at age 61 with abdominal complaints secondary to a hereditary deficiency of C1 inhibitor. The patients' symptoms were due to gastrointestinal angioedema, resulting from episodic unregulated complement activation. The biochemical mechanism of this unusual syndrome and its diagnostic importance are discussed. A C1 inhibitor deficiency should be considered in patients with unexplained abdominal symptoms suggestive of intestinal pseudo-obstruction. PMID- 8438856 TI - Eradication of Helicobacter pylori normalizes serum gastrin concentration and antral gastrin cell number in a patient with primary gastrin cell hyperplasia. AB - A 60-yr-old man with longstanding duodenal ulcer was found to have hyperchlorhydria, moderate fasting hypergastrinemia, and markedly exaggerated meal-stimulated gastrin release. Antral tissue specimens showed the proliferation of gastrin cells and increased gastrin content, and he was found to have Helicobacter pylori infection in the antral mucosa. His illness was diagnosed as primary gastrin cell hyperplasia with H. pylori infection. Eradication of H. pylori normalized not only gastrin hypersecretion but also gastrin cell hyperplasia. These results indicate that H. pylori infection could be one of the causes of this syndrome. PMID- 8438857 TI - The value of precise preoperative localization of colonic arteriovenous malformation in childhood. AB - Massive hemorrhage from the gastrointestinal tract in a 12-yr-old boy caused by a congenital atypically located colonic arteriovenous malformation is described. Guided and "clean" resection of the involved colon was possible due to preoperative selective angiography, which proved to be the most efficient diagnostic tool. Histologic documentation of this rare pathology in childhood is presented, and the classification and features of the disease are briefly reviewed. PMID- 8438858 TI - Primary aortoduodenal fistula: a unique presentation of a pseudoaneurysm associated with cystic medial necrosis. AB - A 42-yr-old man who exsanguinated from an acute upper gastrointestinal bleed was found to have a primary aortoduodenal fistula on postmortem examination. The fistula arose in an aortic pseudoaneurysm associated with cystic medial necrosis. Although there was no suggestion of Marfan's syndrome on physical examination, there was cystic medial necrosis of not only the involved aorta, but also other systemic arteries. Primary aortoduodenal fistula is a rare cause of acute upper gastrointestinal bleeding and is usually associated with atherosclerotic disease of the aorta. This is the first report of a pseudoaneurysm associated with cystic medial necrosis presenting as an aortoduodenal fistula. PMID- 8438859 TI - Diagnostic difficulty in a case of heterotopic pancreatic tissue of the ileum. AB - We describe a case of heterotopic pancreatic tissue of the ileum causing acute gastrointestinal tract bleeding. It was initially clearly demonstrated as an ileal polyp preoperatively by radiologic means. Exploratory surgery was performed, and the segment of ileum containing the mass was resected. Histopathologic examination of the lesion revealed heterotopic pancreatic tissue of Heinrich type II. There was no histological evidence of acute or chronic pancreatitis, but erosion was confirmed at the tip of the mass. Even symptomatic heterotopic pancreatic tissue of the ileum may give difficult diagnostic problems. The present case is reported to show the possibility of diagnosing rare abnormalities of the ileum. PMID- 8438860 TI - Methotrexate for PBC: hope or hype? PMID- 8438861 TI - Tarnish on the golden scalpel? PMID- 8438862 TI - Features of portal hypertensive gastropathy. PMID- 8438863 TI - Measurement of stool color by paint samples. PMID- 8438864 TI - Pancreatitis in AIDS patients treated with didanosine. PMID- 8438865 TI - Vignettes of the past: clysters, fumagators, and the fundament. PMID- 8438866 TI - Pancreatitis associated with naproxen. PMID- 8438867 TI - Fulminant hepatic failure in an AIDS patient: possible zidovudine-induced hepatotoxicity. PMID- 8438868 TI - alpha-Interferon therapy for hepatitis C virus chronic infection with mixed cryoglobulinemia. PMID- 8438869 TI - Annular pancreas with dilated biliary and pancreatic ducts. PMID- 8438870 TI - Acute painless pancreatitis as a rare complication in Legionnaires disease. PMID- 8438871 TI - Leiomyoma of the common bile duct. PMID- 8438872 TI - Calcified retroperitoneal enteric duplication cyst. PMID- 8438873 TI - Severe weight loss, renal failure, and metabolic alkalosis due to duodenal adenomyoma. PMID- 8438874 TI - Clinical and prognostic significance of in vivo differentiation in acute myeloid leukemia. AB - Bromodeoxyuridine (BrdU) was administered to 86 newly diagnosed patients with standard risk acute myeloid leukemia (AML) prior to starting induction therapy and the labeling index (LI), durations of S-phase (Ts), and the cell cycle (Tc) of myeloblasts were determined. Induction therapy with cytosine arabinoside and daunomycin was subsequently started. Bone marrow biopsies were obtained on days 6 and 17 and weekly thereafter, and were treated with a monoclonal anti-BrdU antibody to determine the fate of cells labeled on day 0 by BrdU. BrdU labeled granulocytes indicating the presence of in vivo differentiation (Diff+) were identified in 48 patients ranging from 1+ (1-10 labeled cells) to 4+ (greater than 31 labeled granulocytes). When compared to 38 differentiation negative (Diff ) patients, Diff+ group had longer Ts (14.5 hr vs. 10.95 hr, P = 0.015) and Tc (59.7 hr vs. 41.7 hr, P = 0.017). Remission duration was significantly longer (no median) for 3-4+ Diff+ as compared to Diff- (median = 220 days) patients (Wilcoxon P = 0.04). We conclude that the detection of in vivo differentiation in AML patients indicates a favorable long-term prognosis either due to the presence of a substantial amount of normal residual hematopoiesis prior to starting induction therapy or due to the ability of leukemic cells to undergo differentiation. PMID- 8438876 TI - Flow cytometric analysis of the ploidy of normoblasts in the peripheral blood of patients with beta-thalassemia. AB - The chronic severe anemia of patients with beta-thalassemia major stimulates extensive erythropoiesis, which results in circulating nucleated normoblasts. We devised a dual staining flow cytometric procedure in order to analyse the cell cycle and ploidy of these normoblasts. Peripheral blood cells of O blood-group type were first stained with Fluorescein Isothiocyanate (FITC)-conjugated anti-H lectin which labels erythroid cells (RBC and normoblasts) by green fluorescence, and then with propidium iodide (PI) which binds to DNA and thereby labels nucleated cells (leukocytes and normoblasts) by red fluorescence. The leukocytes and normoblasts present in the blood sample of thalassemic patients could be distinguished and "gated" based on their green fluorescence. The PI (red) fluorescence, i.e., the DNA histogram of each population, was thus obtained. The results indicated no statistically significant difference in the PI fluorescence of these two populations. Thus, in spite of the abnormal erythropoiesis in beta thalassemia, the resultant orthochromatic normoblasts are normal with respect to their DNA content. PMID- 8438875 TI - Alpha granule proteins in type I von Willebrand's disease. AB - Platelet von Willebrand factor (vWf) is located in the alpha granules. Individuals with type I von Willebrand's disease (vWd) with prolonged bleeding times are best discriminated from those who have normal bleeding times by the normal level of platelet vWf ristocetin cofactor activity (vWf activity) and, to a lesser extent, by their platelet vWf antigen content. We have studied the content of adhesive proteins and platelet factor-4 (PF-4), and beta thromboglobulin (beta TG) in the platelet alpha granules of types I and III vWd patients to determine if other alterations in alpha granule contents of proteins occur in vWd. We found that type I vWd patients with prolonged or normal bleeding times could not be differentiated on the basis of their platelet levels of beta TG, PF-4, fibronectin, or fibrinogen. The levels of the alpha granule constituents in the type I vWd patient were similar to normal except for the platelet fibrinogen concentration. Patients with type I vWd, regardless of the level of platelet vWf activity of antigen, had increased levels of platelet fibrinogen. The patients with type III vWd who had undetectable levels of platelet and plasma vWf also had increased levels of platelet fibrinogen. In our study we could not attribute the variation in the platelet vWf activity and antigen in type I vWd to the size of the alpha granule pool as determined by the measurement of other alpha granule proteins. The mechanism(s) of increased platelet fibrinogen in these vWd patients is at present unknown. PMID- 8438877 TI - Plasminogen activators and their inhibitors in leukemic cell homogenates. AB - Plasminogen activator (PA) and PA inhibitor (PAI) were measured in homogenates of leukemia cells. Both PA and PAI levels were higher in non-lymphoblastic leukemia than in lymphoblastic leukemia. The levels were below the sensitivity of determination in chronic myelocytic leukemia (CML) but showed significant increases in blast crisis (CML,bc). The level of the tissue type PA (t-PA) antigen was highest in acute myeloblastic leukemia (AML) and that of the urokinase type PA (u-PA) was highest in acute promyelocytic leukemia (APL). The PAI-I antigen showed no marked cell specificity, but the PAI-II antigen was markedly increased in myelomonocytic leukemia and acute monocytic leukemia (AMoL). From these findings, various PAs and PAIs are considered to be present in leukemia cells and to be involved in hemostatic disorders, thus they are of diagnostic value in leukemia. PMID- 8438878 TI - Evaluation of bone marrow iron stores in anemia associated with chronic disease: a comparative study of serum and red cell ferritin. AB - The serum ferritin (SERFER) may be elevated and misleading in the setting of chronic disease (chronic inflammation, liver disease, and neoplasm). The red cell ferritin (RBCFER) may be more stable in clinical situations that affect the SERFER. We compared the ability of SERFER and RBCFER to assess iron stores in these settings. Iron stores were defined by bone marrow aspirate staining. We studied 120 anemic (Hb < 14 g/dl) male patients. Twenty-eight (23%) were iron deficient based on the absence of marrow iron. The SERFER correlation with marrow iron stores (r = 0.58; P < 0.001) was better than the RBCFER (r = 0.36; P < 0.001). Cutoff values for the diagnosis of iron deficiency were determined by chi square analysis (SERFER < 70 ng/ml; RBCFER < or = 4 ag/RBC). The sensitivity for detecting iron deficiency with SERFER (0.60) was less than RBCFER (0.82). The specificity of SERFER (0.90) was slightly better than RBCFER (0.83). Neither difference reached statistical significance (P > 0.05). The positive predictive value between the two assays was the same (SERFER 0.65 vs. RBCFER 0.59). The combination of SERFER < 70 ng/ml with RBCFER < or = 4 ag/RBC was more specific (0.97) when compared with the SERFER alone (0.90) (P = 0.04). In addition, the potential of this combination to predict iron deficiency (0.82) was higher than that seen with either SERFER (0.65) or the RBCFER (0.59). Our findings show that the RBCFER as a single assay is not anymore accurate than the SERFER. However, we find that the RBCFER can effectively complement the SERFER to either predict iron depletion or confirm the presence of bone marrow iron. PMID- 8438879 TI - Improved or fatal acute disseminated intravascular coagulation in systemic lupus erythematosus. AB - To analyze the outcome of systemic lupus erythematosus (SLE) associated with acute disseminated intravascular coagulation (DIC) and also to clarify the clinical factor(s) contributing to the outcome, we retrospectively investigated 120 SLE patients treated between 1981 and 1991. Eight of these patients (6.7%) developed acute DIC; four recovered and the other four died within 2 weeks of onset. Infection preceded acute DIC in all these patients. Acute DIC associated with atypical pneumonia was always fatal, while the patients with pharyngitis or urinary tract infection survived when they were treated adequately. Comparison of the dead and surviving groups revealed that the activity of SLE before the onset of DIC, the severity of DIC, and the treatment given for DIC and the coexistent infection were not significantly related to a fatal outcome. However, severe infection such as atypical pneumonia in patients with secondary immunodeficiency was likely to be fatal irrespective of the presence of DIC. PMID- 8438880 TI - Tumor necrosis factor-alpha overproduction in Fanconi's anemia. AB - Various in vitro studies and clinical observations suggest that Fanconi's anemia (FA) patients are unable to detoxify adequately superoxide anions (O2-) released by activated phagocytes. Recent studies have shown that certain lymphokines such as tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) can significantly enhance O2- production by phagocytic cells. To ascertain lymphokine production in FA patients, we measured TNF-alpha and IFN-gamma production in vivo and in vitro. TNF-alpha was detected in the plasma of 16 of 18 FA patients with concentrations ranging from 6 to 131 pg/ml (mean 31 pg/ml). TNF-alpha was detected in only one of 25 control (healthy donor) plasma, and the level was very low (7 pg/ml). IFN-gamma levels in normal and patient plasma were negligible. Spontaneous and phytohemagglutinin (PHA)-induced production of IFN-gamma and TNF alpha by cultured peripheral blood mononuclear cells did not differ significantly between FA patients and normal controls. The significance of overproduction of TNF-alpha in vivo in the pathophysiology of FA is discussed. PMID- 8438881 TI - New assay for the rapid determination of plasma holotranscobalamin II levels: preliminary evaluation in cancer patients. AB - We describe a new and rapid assay for the measurement of plasma B12 bound to transcobalamin II (holotranscobalamin II) using the property of adsorption of the polypeptides of apotranscobalamin II and holotranscobalamin II to the hydrophobic surface of microfine glass particles. Acid-washed microfine glass was used to separate vitamin B12 bound to the glycoproteins transcobalamin I and transcobalamin III (haptocorrin or R binder) from that bound to transcobalamin II. Sephadex gel filtration separation of 57Co-labelled vitamin B12 binders confirmed that > 90% of holotranscobalamin II can be removed from plasma holohaptocorrin by adsorption to microfine glass particles. Since only holotranscobalamin II is capable of delivering vitamin B12 to metabolizing cells, plasma holotranscobalamin II content reflects the availability of B12 to cells. Use of this test in cancer patients undergoing either chemotherapy or radiation therapy revealed evidence of early negative B12 balance that in some instances was induced by the treatment itself. PMID- 8438882 TI - Effectiveness of cryosupernatant therapy in refractory and chronic relapsing thrombotic thrombocytopenic purpura. AB - This report describes objective improvement in two patients with poorly responsive thrombotic thrombocytopenic purpura (TTP) syndromes (with cryosupernatant). The first had a partial response to plasma exchange with whole plasma (fresh frozen plasma; FFP) and responded dramatically when switched to plasma exchange with cryosupernatant replacement. The second had chronic TTP (three relapses in 9 months) that required prolonged courses of exchange with FFP (approximately 1 month each) to achieve remission. Attempts to manage her recurrent TTP with infusion of two units of FFP had been unsuccessful. The latter patient was tried on cryosupernatant infusions (2 units daily) and responded within 4 days. Moreover, she has been in continuous remission for 12 months while receiving 2 units (one to three times per week). These results suggest that cryoprecipitate-poor plasma may offer advantages over whole plasma in the management of both acute and chronic forms of TTP. PMID- 8438883 TI - Hemorrhagic pleural effusion and pleural thickening as a complication of chronic lymphocytic leukemia. AB - We report a case of pleural thickening and hemothorax in a 56-year-old male with B-cell chronic lymphocytic leukemia (CLL). The association of this entity with CLL has not been previously reported. Awareness of this occurrence is essential to appropriate therapy for similar patients with CLL. PMID- 8438884 TI - A mild type of Hb S-beta(+)-thalassemia [-92(C-->T)] in a Sicilian family. AB - Hematological data are presented for an adult Sicilian patient with a mild Hb S beta(+)-thalassemia caused by a C-->T mutation at position -92 of the beta promoter. This mutation was identified by sequencing of amplified DNA and was confirmed by dot-blot analysis with specific probes. A comparison of levels of Hb S and Hb A in Hb S-beta-thalassemia patients with different beta-thalassemia alleles showed great variations; the highest level of Hb A (45%) was recorded in the patient with Hb S-beta(+)-thalassemia [-92(C-->T)] and the lowest (approximately 13%) in patients with Hb S-beta(+)-thalassemia [IVS-II-745 (C- >G)]. Clinical severity is directly related to the level of Hb A present. PMID- 8438885 TI - Zinc abuse and sideroblastic anemia. AB - We report the case of a young woman who presented with anemia and leukopenia. A bone marrow aspirate revealed a marked excess of ringed sideroblasts. A detailed dietary history disclosed excessive zinc intake. High serum zinc and low serum copper concentrations were confirmed. After discontinuation of the zinc supplements, she made a complete hematologic recovery. This report emphasises the importance of trace metals and their role in the development of hematologic abnormalities. PMID- 8438886 TI - Occurrence of T-cell lymphoma in a patient with Philadelphia chromosome-positive chronic myelogenous leukemia with rearrangements of BCR and TCR-beta genes in the lymph nodes. PMID- 8438887 TI - Early paternity and relapse after bone marrow transplantation. PMID- 8438888 TI - Simultaneous occurrence of factor VIIIC inhibitor and lupus anticoagulant. PMID- 8438889 TI - Reduced fibrinolytic state in early respiratory distress syndrome. PMID- 8438890 TI - Low beta 2-glycoprotein I levels in patients with disseminated intravascular coagulation. PMID- 8438891 TI - Low-dose aspirin and bleeding in uremia. PMID- 8438892 TI - Hypoplastic anemia in an infant with human immunodeficiency virus (HIV) infection. PMID- 8438893 TI - Efficiency of alteplase in the treatment of venous and arterial thrombosis in neonates. PMID- 8438894 TI - Pseudohyperkalemia and platelet count in thrombocythemia. PMID- 8438895 TI - Cyclosporine A used as a single drug in the treatment of pure red cell aplasia associated with thymoma. PMID- 8438896 TI - Idiopathic thrombocytopenic purpura with X chromosome abnormality. PMID- 8438897 TI - Altered properties of erythrocytes in the aged. AB - Erythrocytes in the aged have a decreased life span. The properties of the red blood cells of old individuals are compared to those of the cells of young individuals. In young individuals, removal of the normal erythrocyte at the end of its lifespan is determined by a signal(s) due to (1) modified phospholipids, (2) modified carbohydrate residues, and/or (3) modified proteins. Similar changes may occur in the erythrocytes of old individuals but at a greater rate. In particular, the enhanced degradation of band 3 protein by calpain may provide a senescence signal. PMID- 8438898 TI - Long-term high-level expression of human beta-globin occurs following transplantation of transgenic marrow into irradiated mice. AB - When the human beta-globin gene is transferred into the bone marrow cells of live mice, its expression is very low. To investigate the reason for this, we transferred the bone marrow of transgenic mice containing and expressing the human beta-globin into irradiated recipients. We demonstrate that long-term high level expression of the human beta-globin gene can be maintained in the marrow and blood of irradiated recipients following transplantation. Although expression decreased over time in most animals because of host marrow reconstitution, the ratio of human beta-globin transgene expression to endogenous mouse beta-globin gene expression in donor-derived erythroid cells remained constant over time. We conclude that there is no inherent limitation to efficient expression of an exogenous human beta-globin gene in mouse bone marrow cells following marrow transplantation. PMID- 8438899 TI - Induction of hypomagnesemia during Amsacrine treatment. AB - Serious cardiac arrhythmias and QT interval prolongation have been reported following Amsacrine chemotherapy. The underlying mechanism is unknown. In this study, electrolyte and electrocardiographic parameters were prospectively studied in patients with acute myeloid leukemia (AML) treated with an Amsacrine containing combination chemotherapy regime. Data were collected immediately before and at 20 (+20) and 90 (+90) min after commencement of Amsacrine administration. Sixteen episodes were studied in six consecutive patients over a continuous 9 month period. One patient developed asymptomatic ventricular tachycardia during administration. Results from +20 and +90 min were compared with baseline by Wilcoxon matched pairs test. There was no significant change in potassium, albumin, or ionized calcium concentration at +20 or +90 min. The magnesium concentration at +20 min was significantly reduced (mean -0.04 mmol/liter; P < 0.05) but not so at +90 min. Sodium concentration at +20 min was significantly reduced (mean - 1.9 mmol/liter; P < 0.01). Electrocardiographic analysis showed no significant alteration in PR interval or QRS duration. Heart rate fell significantly from baseline, mean change -10 and -8 min-1 at +20 and +90 min, respectively (P < 0.01 for both). Corrected QT interval (QTc) was significantly prolonged at +20 min (+0.05) and +90 min (+0.05) (P = 0.0001 and P < 0.0001, respectively). This study confirms the high incidence of QTc prolongation with Amsacrine administration and suggests that transient hypomagnesemia may contribute to the risk of cardiac arrhythmia in this setting. PMID- 8438900 TI - Abnormalities of von Willebrand factor multimers in drug-associated thrombotic microangiopathies. AB - Six patients with thrombotic microangiopathy associated with drug therapy had serial analyses of von Willebrand factor (vWF) multimeric patterns in their EDTA plasma samples by sodium dodecyl sulfate-1% agarose gel electrophoresis and autoradiography. In the plasma of five patients (one with chronic myelogenous leukemia, two with prostatic cancer, and two with lymphoma), vWF abnormalities were observed during evolution of the thrombotic microangiopathy. These abnormalities were either the presence of unusually large (UL)vWF multimers of the type similar to those found within, and released or secreted by, endothelial cells (three patients) or a relative decrease in the largest plasma vWF multimers of the type that can be induced to attach to platelets (one patient) or both vWF abnormalities in different serial samples (one patient). In the one cardiac transplant patient who did not develop vWF multimeric abnormalities associated with thrombotic microangiopathy, vWF antigen levels were elevated more than threefold. This later individual received therapy with cyclosporin A alone. The other five thrombotic microangiopathy patients received cyclosporin A in combination with other chemotherapeutic agents (two patients); mitomycin-C, along with other chemotherapy (two patients); or multiple chemotherapeutic drugs, but not cyclosporin A or mitomycin C (one patient). The finding of vWF multimeric abnormalities during serial analysis of plasma samples from five of six patients with drug-associated thrombotic microangiopathy suggests the possibility that ULvWF forms derived from damaged or stimulated endothelial cells, along with the largest plasma vWF multimers, may be involved in the intravascular platelet clumping that is an essential part of the pathophysiology of this disorder. PMID- 8438901 TI - Platelet multielemental composition, lability, and subcellular localization. AB - Diagnostic X-ray spectrometry (DXS), based on X-ray fluorescence, was used to quantitate directly the multiple elemental composition of washed, intact human platelets (n = 16), with the following results: K = 3.08 +/- 1.00 mg/g, Ca = 1.18 +/- 0.29 mg/g, Zn = 35 +/- 9 micrograms/g. These values show that washed platelets contain significant pools of K, Ca, and Zn, the latter some 30-60-fold higher than plasma levels. Dialysis of whole platelets against cation exchange resin (Chelex-100) did not extract Ca(II) and Zn(II) sequestered within whole cells. To identify the subcellular locale of the elements, platelet lysate was subjected to 30-70% sucrose gradient ultracentrifugation and subcellular enriched fractions were obtained. Fractions were analyzed by DXS (for elements), electron microscopy (for dense granules), and subcellular markers fibrinogen and von Willebrand factor. In contrast to Ca and K, which accumulate in the dense granules and the cytoplasm, respectively, Zn appears to be distributed in the alpha-granules (40%) and the cytoplasm (60%). The subcellular distribution of Zn(II) is discussed within the context of the sensitivity of platelet response to the availability of Zn(II) and the platelet release reactions following stimulation. PMID- 8438902 TI - Unusually large von Willebrand factor multimers preferentially promote young sickle and nonsickle erythrocyte adhesion to endothelial cells. AB - Sickle red blood cells (RBC) suspended with endothelial cell (EC)-derived unusually large (UL) von Willebrand factor (vWF) multimers, but not large plasma vWF forms, adhered to human venous EC under shear flow conditions. When sickle RBC were separated by density gradient centrifugation, fractions rich in less dense RBC were the most adhesive to EC in the presence of ULvWF. Incubation of sickle RBC with monoclonal antibodies against platelet surface receptors GPIb or GPIIb/IIIa, or with the integrin receptor agonist Arg-Gly-Asp-Ser (RGDS) decreased the ULvWF-mediated sickle RBC adhesion to EC 84%, > 99%, and 90%, respectively. When incubated with EC before the flow studies, anti-GPIb antibody and RGDS inhibited the ULvWF-mediated sickle RBC adhesion to EC. ULvWF also promoted the adhesion to EC of nonsickle RBC (HbAA) from patients with an increased proportion of young erythrocytes. When the EC supernatant was depleted of most vWF forms, young nonsickle RBC adhesion decreased by 90%. Preincubation of young nonsickle RBC with anti-GPIb antibody, anti-GPIIb/IIIa antibody, or RGDS inhibited the ULvWF-mediated young RBC adhesion to EC by 47%, 88%, and 92%, respectively. These data indicate that (1) low-density erythrocyte fractions enriched in young sickle or young nonsickle RBC are capable of binding ULvWF multimers via GPIb-like and GPIIb/IIIa-like receptors; (2) the RBC vWF receptors are lost or modified as erythrocytes age in the circulation; and (3) ULvWF/RBC complexes also bind to EC via a GPIb-like receptor. PMID- 8438903 TI - Comparison of acute myeloid leukemia occurring de novo or preceded by a myelodysplastic stage: differences in cellular DNA content. AB - The DNA content of bone marrow cells in patients with acute leukemia preceded by a myelodysplastic stage (MDS-AML) was compared to that in patients with de novo AML. We studied granulocytes, lymphocytes, monocytes, and blasts/promyelocytes from Feulgen-stained bone marrow smears of 11 patients with de novo AML, ten patients with MDS-AML, and 13 apparently healthy controls. The mean amount of DNA per cell (DNA index; DI) in each cell population was determined using a digital video-based image-analyzing system (CAS-100). Analysis of variance (F test) showed a significant difference in the DNA content between de novo AML on one hand and MDS-AML and controls on the other as regards to blasts/promyelocytes (P < 0.01), lymphocytes (P < 0.05), and monocytes (P < 0.01), respectively. In three of 11 (27%) patients with de novo AML, a lower than normal limit DI was found both in immature and mature bone marrow cells. Patients with MDS-AML had those of DI values similar to normal controls. In consequence, a significantly reduced mean DI was found in patients with de novo AML in blasts/promyelocytes (P < 0.01), and monocytes (P < 0.05) compared to both normal controls and MDS-AML. Together with data published separately, suggesting differences in granulocyte morphology, clonality, and HLA-DR expression, these data suggest biological differences between the two diseases. PMID- 8438904 TI - Addition of serum from patients with collagen diseases increases to cultured human endothelial cells production and release of von Willebrand factor. AB - The addition of sera from patients with collagen diseases, particularly those with vascular complications, to the supernatant of cultured vascular endothelial cells (EC) in vitro significantly increased the surface and intracellular amounts of von Willebrand factor antigen (vWF:Ag) compared with results obtained with sera from normal healthy subjects. Peak levels of vWF:Ag occurred after 24 h of in vitro culture. Moreover, the amounts of vWF:Ag secreted into the EC supernatant with patient serum added were significantly higher than the amounts secreted into EC supernatant with control serum added, even after 48 h of in vitro culture. Levels of large and intermediate multimers (LIM) of von Willebrand factor (vWF) increased in EC supernatant exposed to serum from patients with collagen diseases as compared with levels in supernatant exposed to serum from normal controls, whereas no significant differences were detected overall between adding the plasma of patients and of normal subjects. In addition, C-reactive protein (CRP) induced a time- and dose-related release of vWF:Ag from EC, while glucocorticoid did not effect the release of vWF:Ag from EC. These results suggest that the sera of patients with collagen diseases, particularly those with vascular complications, stimulate the production and release of LIM of vWF from EC. PMID- 8438905 TI - Spleen in sickle cell anemia: comparative studies of Nigerian and U.S. patients. AB - Anecdotal reports have attributed persistent splenomegaly in African sickle cell anemia (SS) patients to the effects of malaria. However, no comparative studies of patients in malarial and nonmalarial regions have been conducted, and few studies of malaria antibody titers have been reported. In the present study, age- and sex-matched Nigerian patients (n = 310), while it was found only in 8% of U.S. patients (n = 100) from Georgia. There was significant linear correlation between spleen size and Hb levels and with serum immunoglobulins in the Nigerian group. However, serum complement levels (C3 and C4) were not affected by spleen size. In both groups, patients with splenomegaly had fewer circulating pitted red cells than their counterparts without splenomegaly. The mean +/- SE of IgG specific malaria antibody titer among the Nigerian patients without palpable spleens was 9,386 +/- 2,036; 9,334 +/- 2,980 in those with spleens between 1 and 5 cm, 16,201 +/- 4,502 in those with spleens between 6 and 10 cm, and 22,445 +/- 8,456 in those with spleens above 10 cm. Coexistent alpha-thalassemia did not influence the prevalence of splenomegaly among the Nigerian SS patients. This study provides additional evidence that malaria plays a significant role in the persistence of splenomegaly in African patients. PMID- 8438906 TI - Effect of warfarin on arterial thrombogenesis: problems of monitoring. AB - Platelet reactivity to shear stress and collagen and dynamic overall coagulation were measured in vitro from nonanticoagulated blood of 137 patients on warfarin. One hundred five matched, healthy subjects served as controls. Platelet reactivity to both stimuli and contribution of platelets to plasmatic coagulation were significantly inhibited in patients on warfarin. No correlation was found between platelet reactivity and the coagulation status assessed by the international normalized prothrombin time ratio (INR). Despite similar INR, platelet reactivity showed great individual variation. In 98 patients who were followed up for 3 months, measurement of platelet reactivity to shear stress could discriminate between those who had either bleeding or thromboembolic episodes. These findings suggest that monitored platelet function would help in individualizing oral anticoagulant regimens and hence would increase the benefit of therapy without the risk of bleeding complications. PMID- 8438907 TI - Successful bone marrow transplantation in children with severe aplastic anemia using HLA-partially matched family donors. AB - Bone marrow transplantation (BMT) using HLA-partially matched family donors has produced disappointing results (25-30% of long-term survivors) in patients with severe aplastic anemia. We describe two children affected by severe aplastic anemia, not responsive to immunosuppressive therapy, who underwent allogeneic bone marrow transplantation using a HLA-partially matched family donor. Both cases presented 2 first class HLA-antigens (A and B) disparity between donor and recipient. The pretransplant conditioning regimen consisted of cyclophosphamide, thoracoabdominal irradiation, cytosine-arabinoside, and antilymphocyte globulin. As graft versus host disease (GVHD) prophylaxis, Cyclosporine-A was administered at usual dosages for 6 months. A full marrow engraftment was observed in both cases. Only grade I acute GVHD, promptly responsive to corticosteroid therapy, developed with no chronic GVHD. Five months after transplant, both children progressively developed hypertension, renal function impairment, thrombocytopenia, and severe normochromic anemia, with erythropoietin serum levels lower than expected for the haematocrit. After antihypertension treatment and supportive therapy, the clinical picture progressively improved, while treatment with recombinant human erythropoietin completely corrected the long lasting anemia. The two children are alive and well 28 months after the transplant, with a Karnofsky score of 100% and a normal peripheral blood count. The authors suggest that, once immunosuppressive therapy has failed, BMT from donors other than HLA-identical sibling is a feasible approach in children affected by severe aplastic anemia, not having an HLA-identical donor. PMID- 8438908 TI - Combined use of alpha 2B-interferon, chlorambucil, and prednisone in the treatment of previously treated B-chronic lymphocytic leukemia patients. PMID- 8438909 TI - Megadose methylprednisolone for Diamond-Blackfan anemia. PMID- 8438910 TI - Sex-related differences of platelet arachidonate metabolism. PMID- 8438911 TI - Reconstructive procedures for the gynecologic surgeon. AB - In this article are discussed several minor reconstructive pelvic procedures that should be a part of the gynecologic surgeon's armamentarium, specifically the following: Z-plasty, full-thickness skin grafting, skin flaps, W-plasty, and transposition skin flaps. These procedures are essential in both primary reparative and reoperative surgery. These procedures are widely used in other surgical specialties and can be adapted for use in gynecologic surgery. PMID- 8438912 TI - A protocol for routine voluntary antepartum human immunodeficiency virus antibody screening. AB - Human immunodeficiency virus infection among both women of reproductive age and their infants is rapidly increasing. One strategy to address this increase involves the offering of routine voluntary antepartum human immunodeficiency virus antibody counseling and testing. The rationale for this policy is that all prenatal patients are educated about the major modes of viral transmission and encouraged to practice risk reduction behavior. Human immunodeficiency virus infected women receive comprehensive prenatal care; they are referred for medical follow-up, and their infants are identified and targeted for pediatric infectious disease follow-up. During the past 4 years we have developed a protocol for antepartum human immunodeficiency virus screening in our institution. The protocol includes a self-reported human immunodeficiency virus risk behavior profile, pretest counseling conducted by trained human immunodeficiency virus counselors in small groups, written informed consent for human immunodeficiency virus antibody testing, posttest counseling, and education. By following this protocol we have identified and referred for follow-up > 350 human immunodeficiency virus-infected women. PMID- 8438913 TI - Predictors of human gestational length. AB - OBJECTIVES: Our objective was to identify statistically significant variables that determine the length of human gestation. STUDY DESIGN: Multiple linear regression was used to analyze 9355 observations from the Delivery Interview Program, a cross-sectional study conducted from 1977 through 1980 at the Boston Hospital for Women (now called the Brigham and Women's Hospital). RESULTS: Maternal parity, age, and race were found to be the most important variables determining the length of human gestation. Multiparous women, women aged < 19 or > 34 years, and black women were found to have shorter gestations than primiparous women, women aged 19 to 34 years, or white women. CONCLUSION: By means of our linear model the length of pregnancy for women with different risk factors can be estimated more precisely than Naegele's rule allows. PMID- 8438914 TI - Outpatient excisional management of cervical intraepithelial neoplasia. A prospective, randomized comparison between loop diathermy excision and laser excisional conization. AB - OBJECTIVE: The purpose of our study was to compare loop diathermy excision and laser excisional conization with respect to treatment time, reliability, effectiveness, and safety. STUDY DESIGN: Three hundred women with cervical intraepithelial neoplasia attending our colposcopy clinic were randomized to treatment with either loop diathermy excision (group 1, n = 150) or carbon dioxide laser excisional conization (group 2, n = 150), both performed with local anesthesia on an outpatient basis. Student's t or Mann-Whitney test were used to compare continuous data; the chi 2 test was used for categoric data. RESULTS: The mean age, parity, histologic features, depth of excision, and occurrence of residual or recurrent disease were similar; however, the mean time required to complete treatment and hemostasis (2.5 +/- 3.6 vs 24.2 +/- 11.8 min), patient discomfort, blood loss (2.77 +/- 3.76 vs 27.15 +/- 17.51 ml; p < 0.001), and considerable thermal artifact affecting histologic interpretation of excision margins (5 cases vs 25 cases; p < 0.01) were significantly less in group 1 than in group 2. CONCLUSION: In our experience outpatient loop diathermy excision is an equally effective, quicker, safer, and more reliable excisional technique than laser excisional conization. PMID- 8438915 TI - Postpartum perineal morbidity after fourth-degree perineal repair. AB - OBJECTIVE: We attempted to determine the frequency of postpartum perineal morbidity (dehiscence, infection, and rectovaginal fistula) in women after fourth degree perineal repair. STUDY DESIGN: The medical records of 390 women at Parkland Memorial Hospital with fourth-degree perineal repair during 1989 and 1990 were retrospectively reviewed in a case-cohort study. Statistical analysis included chi 2 contingency tables, Fisher exact test, Mann-Whitney test, and analysis of variance. RESULTS: Twenty-one of 390 women (5.4%) had postpartum perineal morbidity. Seven (1.8%) had dehiscence alone, 11 (2.8%) had infection and dehiscence, and 3 (0.8%) had infection alone. Overall there were 18 dehiscences (4.6%) and 14 infections (3.6%) in the total group with perineal morbidity. Two high rectovaginal fistulas were concomitantly detected in women with perineal dehiscence. Only shoulder dystocia, metritis, and postpartum fever occurred significantly more frequently in patients with postpartum perineal morbidity than in women without perineal morbidity. Smoking and human papillomavirus infection were not associated with perineal repair morbidity. CONCLUSIONS: Postpartum perineal morbidity after fourth-degree perineal repair is an uncommon event. It is not predicted by readily preventable antepartum or intrapartum factors. PMID- 8438916 TI - Peripartum heart failure associated with prolonged tocolytic therapy. AB - beta-Adrenergic receptor agonist tocolysis has been reported to cause noncardiogenic pulmonary edema. We report an association between chronic terbutaline therapy and cardiomyopathy in peripartum women. Among 15 gravidas who had peripartum heart failure, 4 had received prolonged terbutaline tocolysis. Although those four patients had completely normalized ventricular function, only 7 of the 11 others recovered. We suggest that gravidas receiving long-term beta sympathomimetic tocolysis undergo close evaluation of cardiac function. PMID- 8438917 TI - Immature lecithin/sphingomyelin ratios and neonatal respiratory course. AB - OBJECTIVE: We hypothesized that the absolute value of an immature lecithin/sphingomyelin ratio, in addition to gestational age and birth weight, contributes significantly to predicting the clinical course of the neonate. The lecithin/sphingomyelin value may therefore enhance clinical decision-making regarding timing of delivery and use of tocolytics in high-risk pregnancies. STUDY DESIGN: One hundred four mother-baby pairs with delivery within 72 hours of an immature lecithin/sphingomyelin determination in the 3-year period immediately before the initiation of surfactant therapy in our hospital were retrospectively reviewed. Stepwise regression was performed for the independent variables of gestational age, birth weight, and lecithin/sphingomyelin values in a linear model to predict total days of respiratory support (oxygen, continuous positive airway pressure, or mechanical ventilation). RESULTS: In the patients without preterm premature rupture of membranes the lecithin/sphingomyelin value was the best predictor of duration of respiratory support (R2 = 0.2426, F = 12.4908, p = 0.011). After gestational age was controlled for, there was a significant inverse correlation between the lecithin/sphingomyelin value and days of respiratory support (F = 4.634, p = 0.031). In the patients with preterm premature rupture of membranes with vaginally collected fluid, however, lecithin/sphingomyelin values did not contribute significantly in predicting duration of respiratory support. Rupture-to-delivery interval and gestational age were the best predictors in this group. CONCLUSION: Although a mature lung profile is the ideal situation, preterm delivery may be indicated in pregnancies complicated by maternal disease or evidence of possible fetal compromise. We conclude that in patients without premature rupture of membranes the absolute value of the immature lecithin/sphingomyelin ratio is a better predictor than gestational age or birth weight of duration of respiratory support and should be considered in timing of delivery. PMID- 8438918 TI - Premature rupture of membranes at < 25 weeks: a management dilemma. AB - OBJECTIVE: A retrospective study was conducted to establish the perinatal and long-term neonatal outcome at 1 year of life (corrected) of pregnancies complicated by premature rupture of membranes before fetal viability. STUDY DESIGN: The outcome of 94 singleton pregnancies admitted from June 1982 to June 1991 with premature rupture of membranes at < 25 weeks' gestation that were managed expectantly were studied. To establish the effect of rupture of membranes, the neonatal outcomes of babies born with birth weights > 500 gm and gestational ages > 24 weeks were compared with those of a similar group of neonates from patients without preterm rupture of membranes and matched by gestational age, birth weight, race, sex, and mode of delivery. The outcome of the surviving neonates at 1 year of life (corrected) was established on the basis of their Bailey mental and psychomotor scores and on the results of neurologic, ophthalmologic, and hearing examinations. RESULTS: The overall incidence of amnionitis was 24%. The median latency period was 10.5 days; in 26% of patients delivery was delayed > 2 weeks. Pulmonary hypoplasia was detected in 5% of patients, and there was no evidence of orthopedic deformities. Survival was achieved in 39 (40%) of neonates; 63% of these survivors were considered to have had normal development at 1 year of life (corrected). CONCLUSION: Premature rupture of membranes at < 25 weeks is associated with a relatively high risk of perinatal mortality and neonatal and long-term morbidity, but a successful outcome can be achieved in about 60% of survivors. PMID- 8438919 TI - Beneficial effects of the combined use of prenatal corticosteroids and postnatal surfactant on preterm infants. AB - OBJECTIVE: Our objective was to test the hypothesis that prenatal maternal corticosteroids would improve the subsequent response of infants to surfactant treatments. STUDY DESIGN: We used the data bases of two recently published large multicenter trials of multidose surfactant treatments to retrospectively evaluate the possible interactions between maternal corticosteroids and randomized surfactant treatments on short-term ventilatory effects, complications of respiratory distress syndrome and prematurity, and 28-day death rates. RESULTS: The combined use of corticosteroids and surfactant significantly decreased overall death and death caused by respiratory distress syndrome relative to either treatment alone. Ventilatory variables at 72 hours were improved in those infants receiving both treatments, and other major complications of prematurity also tended to have decreased incidences. CONCLUSION: The combined use of prenatal corticosteroids, when indicated, and postnatal surfactant improves neonatal outcome. PMID- 8438920 TI - Sexual intercourse during pregnancy and preterm delivery: effects of vaginal microorganisms. The Vaginal Infections and Prematurity Study Group. AB - OBJECTIVE: Our aim was to investigate the influence of vaginal colonization with specific microorganisms on the relationship between sexual intercourse during pregnancy and preterm delivery. STUDY DESIGN: As part of a multicenter, prospective study interviews and physical examinations were conducted with and genital cultures were obtained from women seeking prenatal care from 23 to 26 weeks' gestation. At 31 to 36 weeks interviews were conducted with a randomly selected sample of these patients. RESULTS: Frequent intercourse (defined a priori as once per week or more) at 23 to 26 weeks was associated with a significantly reduced risk of subsequent preterm delivery in women without Trichomonas vaginalis, Mycoplasma hominis, or bacterial vaginosis, possibly because of the relative health and lack of complications in the pregnancies of those women engaging in sexual intercourse. Frequent intercourse was not significantly associated with preterm delivery in women with T. vaginalis, M. hominis, or bacterial vaginosis. Neither T. vaginalis, M. hominis, nor bacterial vaginosis was associated with preterm delivery among women with infrequent intercourse at 23 to 26 weeks. However, T. vaginalis and M. hominis were risk factors for preterm delivery among those with frequent intercourse. CONCLUSIONS: Frequent sexual intercourse by itself is not associated with an increased risk of preterm birth. However, women who are colonized with specific microorganisms and who engage in frequent intercourse are at increased risk of preterm delivery. PMID- 8438922 TI - Plasma concentration of endothelin-1 in women with cocaine-associated pregnancy complications. AB - OBJECTIVE: The purpose of this study was to determine if the plasma concentration of endothelin-1 is elevated in pregnant women abusing cocaine and to determine how these levels differ from those in patients with preeclampsia and in women with uncomplicated pregnancies. STUDY DESIGN: Plasma endothelin-1 levels were measured in 30 women with acute cocaine intoxication, 32 women with preeclampsia, 14 pregnant women with chronic hypertension, 26 women with uncomplicated pregnancies, and 16 nonpregnant individuals. Serial samples after delivery were obtained in 12 women with preeclampsia, 10 with cocaine abuse, 4 with chronic hypertension, and 7 with uncomplicated pregnancies. RESULTS: The mean endothelin 1 concentration in those with cocaine abuse was 18.2 +/- 8.1 pg/ml (95% confidence interval 15.2 to 21.2). This was similar to that in women with preeclampsia (21.1 +/- 5.9 pg/ml, 95% confidence interval 19 to 23.3) (p = 0.2) but significantly different from that in women with chronic hypertension (11.5 +/ 3.6 pg/ml, 95% confidence interval 9.4 to 13.6) (p < 0.001) and women with uncomplicated pregnancies (6.7 +/- 3.9 pg/ml, 95% confidence interval 5.1 to 8.2) (p < 0.001). CONCLUSIONS: Endothelin-1 levels in women abusing cocaine are comparable to those in women with preeclampsia and are significantly higher than those in gravid women with chronic hypertension and women with uncomplicated pregnancies. Elevated levels of endothelin-1 may contribute to some of the pregnancy-related complications in women abusing cocaine. PMID- 8438921 TI - Colony-stimulating factor-1 in primary ascites of ovarian cancer is a significant predictor of survival. AB - OBJECTIVE: Our purpose was to determine whether the concentration of colony stimulating factor in ascites of ovarian carcinoma is a prognostic factor for survival. STUDY DESIGN: Forty-four ascites samples from patients undergoing primary surgery for ovarian carcinoma were measured for colony-stimulating factor 1 by radioimmunoassay. Retrospective analysis of clinical data allowed comparison of accepted prognostic factors to ascites colony-stimulating factor-1 concentration for impact on survival by means of life-table analysis (Kaplan Meier) by the Wilcoxon test and the Cox regression methods. RESULTS: In patients with advanced disease (International Federation of Gynecology and Obstetrics stages III and IV, n = 37) ascites colony-stimulating factor-1 concentration levels below a critical cutoff of 8.59 ng/ml were associated with longer overall survival (p < 0.05) and were a better predictor of survival than any other prognostic factor except zero residual disease after cytoreduction. International Federation of Gynecology and Obstetrics stage, tumor histologic type, malignant cells in fluid, grade of tumor, age, and performance status at presentation were not predictive of outcome. CONCLUSION: Colony-stimulating factor-1 in ascites may be an independent indicator of prognosis in patients with epithelial ovarian cancer. PMID- 8438923 TI - Humerus and femur length shortening in the detection of Down's syndrome. AB - OBJECTIVE: Our purpose was to determine the utility of screening for humerus and femur length shortening in prenatal detection of Down's syndrome (trisomy 21). STUDY DESIGN: On the basis of the biparietal diameter, predicted humerus and femur lengths were derived from a sample control group of 350 karyotypically normal fetuses. The regression formulas were prospectively applied to 45 consecutive fetuses with Down's syndrome and 942 fetuses with normal karyotypes. Ratios of measured humerus length/predicted humerus length and measured femur length/predicted femur length were calculated for each fetus. RESULTS: Eleven of 45 (24.4%) fetuses with Down's syndrome had short humerus (measured humerus length/predicted humerus length ratio of < or = 0.89), and 11 (24.4%) had short femur (measured femur length/predicted femur length ratio of < or = 0.91. In comparison, among 942 karyotypically normal fetuses only 43 (4.5%) showed short humerus and 44 (4.7%) showed short femur (p < 0.05). Fetuses with both short humerus and short femur carried an 11-fold greater risk of Down's syndrome (risk ratio = 11.1; 95% confidence interval = 5.0 to 25.0). CONCLUSION: Prenatal ultrasonographic detection of short humerus to short femur, or both significantly increase the risk of Down's syndrome; this information may be useful in screening programs. PMID- 8438924 TI - Oncofetal fibronectin in patients with false labor as a predictor of preterm delivery. AB - OBJECTIVE: Our objective was to determine whether fetal fibronectin is a discriminator for preterm labor and early delivery in women who have intact membranes and uterine activity. STUDY DESIGN: In our prospective study 28 women between 24 and 34 weeks' gestation with regular, persistent uterine contractions (> 10/hr) and intact membranes were assessed for presence of fetal fibronectin. A Dacron swab was applied to the external os for 10 seconds. The cervix was < or = 1 cm, and all patients were diagnosed as having false labor. The assay was performed by using monoclonal antibody FDC-6 to bind fetal fibronectin. RESULTS: Of the 28 patients with false labor, 14 had a positive fetal fibronectin, and all had preterm labor (specificity and positive predictive value 100%). Of these, nine delivered preterm, yielding a specificity and positive predictive value of 72% and 64%, respectively. Among the 14 women with a negative fetal fibronectin, only four developed preterm labor (sensitivity 78%, negative predictive value 71%). One patient delivered preterm at 34 weeks (sensitivity 90% and negative predictive value 93%). CONCLUSIONS: A positive fetal fibronectin in women who have false labor indicates a significant risk for preterm labor and early delivery. A negative fetal fibronectin is a reassuring sign. PMID- 8438925 TI - Trial of labor after a one- or two-layer closure of a low transverse uterine incision. AB - In the subsequent labor and delivery of 292 women who had a prior low transverse cesarean section the incidence of scar separation was low and was not affected by the method of uterine closure. A low transverse incision closed in one continuous layer should not preclude a subsequent trial of labor. PMID- 8438926 TI - Fetal growth retardation: associated malformations and chromosomal abnormalities. AB - OBJECTIVE: Our objective was to determine the incidence and pattern of chromosomal abnormalities in fetal growth retardation. STUDY DESIGN: Blood karyotyping was performed in 458 fetuses referred to us for further assessment of growth retardation at 17 to 39 weeks' gestation. RESULTS: The fetal karyotype was normal in 369 and abnormal in 89 (19%) of the cases. The most common chromosomal defect in the group referred at < 26 weeks' gestation was triploidy; in those referred at > or = 26 weeks, it was trisomy 18. The incidence of fetal autosomal chromosome aberrations increased, whereas the incidence of triploidy did not change, with maternal age. Ninety-six percent of chromosomally abnormal fetuses had multisystem fetal defects that were characteristic of the different types of chromosomal abnormalities. Compared with those fetuses with a normal karyotype, the chromosomally abnormal group had a higher mean head circumference/abdominal circumference ratio, a higher incidence of normal or increased amniotic fluid volume, and normal waveforms from the uterine or umbilical arteries or both. CONCLUSION: The findings of the different types of chromosomal abnormalities and their ultrasonographically detectable phenotypic expression provide the background for prospective studies to determine the incidence of chromosomal abnormalities in unselected populations of small-for-gestational-age fetuses. PMID- 8438927 TI - Seeking early medical attention after vaginal bleeding will not assure mild disease in postmenopausal endometrial carcinoma. AB - We compared the length of time between the onset of vaginal bleeding and (1) initial visit to a physician and (2) hysterectomy in patients with endometrial carcinoma (mild vs advanced disease). There was no difference in these times. We conclude that patients with advanced endometrial carcinoma do not delay seeking medical attention when compared with patients with mild disease. PMID- 8438928 TI - Rapid diagnosis and classification of hydatidiform moles with polymerase chain reaction. AB - OBJECTIVE: The purpose of our study was to determine whether the polymerase chain reaction can be used to diagnose the gestational trophoblastic disease hydatidiform mole and distinguish between partial, monospermic complete, and dispermic complete hydatidiform mole. STUDY DESIGN: In 20 cases of well characterized hydatidiform mole, deoxyribonucleic acid was amplified from parental and molar samples by using primers for the variable number tandem repeat sequence YNZ22 and for sex chromosome-specific sequences. RESULTS: Polymerase chain reaction amplification of the YNZ22 polymorphism identified contributions from both parents in 5 of 7 partial hydatidiform moles. Nine of 13 complete hydatidiform moles were shown to be androgenetic by using primers for the YNZ22 polymorphism. Two of the complete hydatidiform moles were classified as dispermic on the basis of Y chromosome-specific sequences. CONCLUSION: Polymerase chain reaction was shown to be a rapid and accurate method of identifying parental contributions to the molar genome and thus has the potential to be used for diagnosis and classification of hydatidiform moles. PMID- 8438929 TI - Placental sulfatase deficiency and congenital ichthyosis with intrauterine fetal death: case report. AB - Placental sulfatase deficiency and congenital ichthyosis are two manifestations of an X-linked recessive inborn error of metabolism. This uncommon disorder can be diagnosed antenatally by maternal urinary steroid assays. A case with an affected sibling is presented, and the disorder's association with fetal death and failure to induce labor is discussed. PMID- 8438930 TI - Hyaline membrane disease: the role of ethnicity and maternal risk characteristics. AB - OBJECTIVE: Our objective was to explore the association between maternal ethnicity and maternal antepartum complications of pregnancy, maternal sociodemographic factors, and newborn characteristics with the incidence of hyaline membrane disease. STUDY DESIGN: By using a retrospective cohort analysis the incidence of hyaline membrane disease was determined for 2295 preterm infants. The study population consisted of all live, inborn infants delivered vaginally from 1982 to 1987. Statistical differences were assessed by use of chi 2 and Student's t tests. A logistic regression procedure determined the relationship of ethnicity and hyaline membrane disease after the study was controlled for all other significant population differences. RESULTS: The differences between black and white populations in marital status, were statistically significant years of education, prolonged rupture of membranes, anemia, and chronic hypertension were statistically significant. Infants of black mothers were diagnosed with hyaline membrane disease less often than infants of white mothers (overall and at each gestational age interval). After the study was controlled for population differences, infants of black mothers were still found to experience hyaline membrane disease less often. CONCLUSION: These data suggest that hyaline membrane disease occurs less frequently, is less severe, and is accompanied by fewer related complications in black preterm infants. PMID- 8438931 TI - Uterine contractions after antibiotic therapy for pyelonephritis in pregnancy. AB - OBJECTIVE: The purpose of our study was to investigate the pathogenesis of preterm labor in pyelonephritis, we determined the number of uterine contractions occurring in patients with pyelonephritis before and after antibiotic therapy. STUDY DESIGN: We recorded the uterine contractions before and after antibiotic administration in 30 patients with acute pyelonephritis at Lyndon B. Johnson Hospital in Houston. Exclusion criteria were cervical dilatation > or = 4 cm, < 26 weeks' gestation, antibiotics within 7 days, clinical intraamniotic infection, rupture of membranes, or other maternal infection. Statistical analysis was by Kruskal-Wallis analysis of variance and Wilcoxon rank sum tests. RESULTS: The patients averaged eight contractions per hour on admission. The contraction rate significantly increased in hours +1 to +4 after antibiotic administration. The increase in uterine contractility occurred in patients with urinary tract gram negative isolates. CONCLUSIONS: Pregnant women with pyelonephritis resulting from gram-negative bacteria increase their rate of uterine contractility after antibiotic treatment. This observation may be important in understanding the pathogenesis of preterm labor in pyelonephritis. PMID- 8438932 TI - The effect of sustained exercise on follicular phase levels of 17 beta-estradiol in recreational athletes. AB - OBJECTIVE: Our purpose was to test the hypothesis that sustained exercise elevates circulating levels of 17 beta-estradiol in an intensity-dependent manner. STUDY DESIGN: Blood samples were obtained in the follicular phase of the menstrual cycle from 75 female recreational athletes before and immediately after 20 minutes of aerobics or running at their usual exercise intensity. RESULTS: The levels of 17 beta-estradiol rose after exercise 97% of the time. At exercise intensities between 50% and 88% of maximum capacity there was a direct linear relationship (r = 0.57) between exercise intensity and magnitude of increase in estradiol levels. A similar relationship was not present for cortisol. CONCLUSION: Sustained exercise produces an intensity-dependent increase in the levels of 17 beta-estradiol that probably reflects decreased hepatic clearance caused by the fall in splanchnic blood flow. Thus the magnitude of the increase in the level of 17 beta-estradiol can be used as a rough index of the exercise induced decrease in splanchnic blood flow. PMID- 8438933 TI - Maternal placental vasculopathy and infection: two distinct subgroups among patients with preterm labor and preterm ruptured membranes. AB - OBJECTIVE: Our aim was to find out whether patients delivered preterm because of preterm labor or preterm premature rupture of membranes can be categorized according to clinical characteristics and placental pathologic findings. STUDY DESIGN: We performed a case-control study of 105 patients who were delivered preterm, 42 because of preterm labor and 63 because of premature rupture of membranes, and 105 patients who were delivered at term after uncomplicated pregnancies. RESULTS: Maternal placental vascular lesions were present in 14 (34.1%) patients with preterm labor, 19 (35.1%) patients with premature rupture of membranes, and 9 (11.8%) control patients (odds ratios 3.8 and 4.0, 95% confidence intervals 1.3 to 11.1 and 1.5 to 10.8, p = 0.0065 and 0.0022, respectively). Infection of the products of conception was found in 16 patients (38%) with preterm labor, 23 patients (36.5%) with premature rupture of membranes, and 19 control patients (18%) (odds ratios 2.7 and 2.6, 95% confidence intervals 1.1 to 6.6 and 1.2 to 5.6, p = 0.017 and 0.01, respectively). Patients with maternal placental vasculopathy had significantly different characteristics compared with those of infected patients. CONCLUSIONS: It is possible to identify two subgroups of patients among those who are delivered preterm because of preterm labor or premature rupture of membranes, one with infection of the products of conception and another with maternal placental vasculopathy. PMID- 8438934 TI - Increased chemotactic activity of peritoneal fluid in patients with endometriosis. AB - OBJECTIVE: Our purpose was to investigate the ability of the peritoneal fluid of patients with endometriosis to induce chemotaxis of neutrophils and macrophages. STUDY DESIGN: Peritoneal fluid samples of patients with endometriosis (n = 20), normal fertile controls (n = 12), or patients with medical suppression (n = 8) were evaluated for chemotactic activity. Results of chemotactic activity were analyzed by analysis of variance. RESULTS: Peritoneal fluid of patients with endometriosis demonstrated a significantly higher chemotactic activity than that of patients without endometriosis or with medical suppression. Patients who had received medical treatment had the lowest chemotactic activity. (p < 0.001 for endometriosis vs control or treatment patients, p = 0.005 for control group vs treatment group). CONCLUSIONS: Patients with endometriosis have a higher chemotactic activity in their peritoneal fluid; prior medical treatment significantly reduces this activity. This chemotactic factor has an estimated weight of 20 kd. The nature and source of this chemotactic factor remains to be determined. PMID- 8438935 TI - Urinary endothelin-1: not a useful marker for preeclampsia. AB - Urinary endothelin-1 levels were assayed from 50 gravidas with preeclampsia and 11 with normotension in the third trimester of pregnancy. Urinary endothelin-1 levels (mean +/- SEM) were similar between gravidas with normotension and preeclampsia (62.7 +/- 7.5 vs 79.8 +/- 9.3 fmol/mg urinary creatinine, respectively). Urinary endothelin-1 excretion is not significantly increased in patients with preeclampsia and therefore not a good marker for preeclampsia. PMID- 8438936 TI - The use of color flow Doppler ultrasonography to diagnose umbilical cord entanglement in monoamniotic twin gestations. AB - OBJECTIVE: Our purpose was to investigate the use of color flow Doppler ultrasonography to identify umbilical cord entanglement. STUDY DESIGN: Our case series consisted of three monoamniotic twin gestations. Color flow Doppler was used prospectively to study the umbilical cords. RESULTS: Apparent "branching" of the umbilical artery, with evidence of two different heart rates in the two segments of the branch, was seen in all cases. Compression of the umbilical vein was identified by extremely high blood velocity. CONCLUSIONS: Color flow Doppler is useful in the identification of umbilical cord entanglement in monoamniotic twin pregnancies and may provide a method of monitoring the fetuses for evidence of cord compression. PMID- 8438937 TI - Possible physiologic role of calcitonin gene-related peptide in the human uterine artery. AB - OBJECTIVE: The purpose of our study was to determine the potential physiologic role of calcitonin gene-related peptide as an endogenous vasodilator of human uterine arteries during pregnancy. STUDY DESIGN: Isolated, suffused uterine arteries from pregnant patients (n = 9) and nonpregnant patients (n = 19) were used in the study. RESULTS: Calcitonin gene-related peptide (1 nmol/L to 0.1 mumol/L) produced a concentration-dependent relaxation of norepinephrine (1 mumol/L)-induced contractions. The values of calcitonin gene-related peptide that inhibited norepinephrine-induced contractions by 50% were 0.9 +/- 0.7 nmol/L (n = 8) and 6.5 +/- 1.5 nmol/L (n = 12) in pregnant and nonpregnant arteries, respectively. The calcitonin gene-related peptide-induced relaxation was not affected by propranolol (1 mumol/L), indomethacin (5 mumol/L), methylene blue (10 mumol/L), or by the removal of the endothelium. The relaxant effect of calcitonin gene-related peptide was inhibited by human calcitonin gene-related peptide(8 37). The endogenous levels of calcitonin gene-related peptide were 110.2 +/- 13.5 pmol/L/gm wet weight in pregnant arteries and 14.8 +/- 3.2 pmol/L/gm wet weight in nonpregnant arteries. CONCLUSIONS: These results demonstrate that the vasodilatory effect of calcitonin gene-related peptide is mediated by calcitonin gene-related peptide1 receptors and does not involve beta-adrenoceptors, vasodilator prostanoids, increased levels of guanosine 3',5'-cyclic monophosphate, or endothelium-derived relaxing factor. The findings that calcitonin gene-related peptide acts as a potent dilator and that pregnancy increases both the sensitivity to calcitonin gene-related peptide and the endogenous levels of calcitonin gene-related peptide support the view that calcitonin gene-related peptide has a physiologic role in dilating the uterine vasculature, especially during pregnancy. PMID- 8438938 TI - The temporal relationship between maternal blood and amniotic fluid glucose levels. AB - OBJECTIVE: Our purpose was to examine the temporal relationship between maternal blood and amniotic fluid levels. STUDY DESIGN: Glucose levels were measured on 158 paired samples from maternal plasma and amniotic fluid obtained from healthy women undergoing genetic amniocentesis at 15 to 20 weeks of gestation. The samples of venous blood and amniotic fluid were drawn at different time intervals, randomly assigned from 0 to 200 minutes. Linear regression analysis was used to test the relationship. The significance was tested by two-tailed t test. RESULTS: A good significant correlation (r = 0.78, p < 0.01 and r = 0.67, p < 0.05) was found at 21- to 40- and 121- to 140-minute intervals, respectively. CONCLUSION: The amniotic fluid glucose level reflects the maternal blood glucose levels at specific lag times. PMID- 8438939 TI - Fetal plasma erythropoietin concentration in severe growth retardation. AB - OBJECTIVE: The aim of this study was to determine whether hypoxemia induces an increase in plasma erythropoietin concentration in human fetal life and, if so, whether this response stimulates fetal erythropoiesis. STUDY DESIGN: The plasma erythropoietin concentration in blood samples from 33 small-for-gestational-age fetuses at 26 to 38 weeks' gestation was measured. Measurements were compared with the reference range for gestation, and associations with PO2, pH, and erythroblast and erythrocyte counts were examined. RESULTS: The mean plasma erythropoietin concentration in the small-for-gestational-age fetuses was significantly increased, and the degree of increase was significantly associated both with fetal acidemia and, more strongly, with fetal erythroblastosis. CONCLUSION: Erythropoietin production in response to tissue hypoxia occurs from at least 26 weeks' gestation with measurable physiologic effects on erythropoiesis. Furthermore, more accurate assessment of tissue oxygenation may be obtained by measuring the erythroblast count rather than the blood pH. PMID- 8438940 TI - Long-term effects of hormone replacement therapy on the uterus and on uterine circulation. AB - OBJECTIVE: Our purpose was to study the effects of postmenopausal hormone replacement therapy on the uterus and uterine circulation. STUDY DESIGN: The study population consisted of 432 women, 58 to 59 years of age. Color Doppler ultrasonography with a transvaginal probe was used to measure the size of the uterus and the uterine artery pulsatility index. RESULTS: The mean endometrial thickness in group 1 (controls without hormone replacement therapy) was significantly thinner compared with group 2 hormone replacement therapy and with group 3 after discontinuance of hormone replacement therapy. The mean uterine artery pulsatility index was lower both in group 2 and 3 compared with group 1. When hormone replacement therapy was initiated 2 to 10 years after menopause, the endometrial thickness did not differ from that among those who had started hormone replacement therapy earlier, but the pulsatility index was significantly higher. There was positive correlation between the size of the uterus and the pulsatility index in group 1, but the correlation was negative in group 2. In general, the duration of hormone replacement therapy had no effect on the pulsatility index. Estrogen users had a significantly thicker endometrium compared with estrogen-progestogen users. The pulsatility index was highest in the estrogen users with progestogen added every month. CONCLUSION: The duration, onset of treatment in relation to menopause, discontinuance of hormone replacement therapy, and mode of treatment modify both the normal postmenopausal endometrial thickness and the uterine vascular resistance. PMID- 8438941 TI - Amniorrhexis lowers the incidence of positive cultures for group B streptococci. AB - OBJECTIVE: Our purpose was to determine the effect of amniorrhexis on cultures for group B streptococci. STUDY DESIGN: Intrapartum vaginal cultures for group B streptococci were obtained before and after rupture of membranes in 166 women; in addition, rectal cultures were obtained from the last 35 patients. RESULTS: Before rupture of membranes 49 of 166 (30%) of the vaginal cultures were positive for group B streptococci; only 28 of 166 (17%) remained positive after rupture of membranes (p = 0.0009). Similarly, before rupture of membranes 10 of 35 (30%) rectal cultures were positive, whereas only three of 35 (0.9%) remained positive for group B streptococci after rupture of membranes (p = 0.03). CONCLUSION: The prevalence of positive genital cultures for group B streptococci is significantly lower immediately after rupture of membranes. PMID- 8438942 TI - Fetal sacral length in the ultrasonographic assessment of gestational age. AB - OBJECTIVE: Our purpose was to establish a nomogram of fetal sacral length throughout gestation and to assess its value in cases of abnormal fetal growth. STUDY DESIGN: A prospective cross-sectional study of 506 singleton fetuses with normal growth between 15 and 41 weeks' gestation was performed. Regression analyses were performed on sacral length, gestational age, biparietal diameter, head circumference, and femur length. The sacral length in 80 singleton gestations with abnormal growth (40 > 90th percentile and 40 < 10th percentile for gestational age) were compared with the nomogram. RESULTS: Linear relationships between gestational age and sacral length, biparietal diameter, head circumference, and femur length were demonstrated. Sacral length (centimeters) as a function of gestational age (weeks) was expressed by the regression equation: Sacral length = -0.108 + 0.102 Gestational age, with a Pearson correlation coefficient of R2 = 0.959. The sacral length of all 80 fetuses with abnormal growth demonstrated the same relationship to gestational age as did the 506 normal controls. CONCLUSION: This study defines the normal limits of sacral length; demonstrates a high correlation between sacral length, gestational age, and other standard measurements of fetal growth; and indicates that sacral length can predict gestational age, irrespective of fetal nutritional status. PMID- 8438943 TI - A five-year experience with second-trimester induced abortions: no increase in complication rate as compared to the first trimester. AB - OBJECTIVE: Our purpose was to compare the complication rate of first-trimester suction curettage with that of second-trimester dilation-and-evacuation abortions in the same clinical setting. STUDY DESIGN: Retrospective analysis (chart review) of the 3772 induced abortions performed between 1986 and 1990 at the Family Planning Clinic of the Centre Hospitalier Universitaire de Sherbrooke, Quebec, Canada. RESULTS: Among the 3355 cases with known follow-up (89%), the complication rate was 5.1% for the 2908 suction curettages at < 15 weeks' gestation compared with 2.9% for the 447 dilation-and-evacuation procedures at 15 to 20 weeks' gestation. Serious complications were few and not increased among patients undergoing dilation and evacuation. CONCLUSION: A careful approach to second-trimester dilation-and-evacuation procedures can make them comparatively as safe as suction curettages, contrary to common belief derived from large surveys done in the late 1970s. PMID- 8438944 TI - Absent end-diastolic flow velocity waveforms in the umbilical artery--the subsequent pregnancy. AB - OBJECTIVE: Our purpose was to assess the recurrence risk, course, and outcome of subsequent pregnancies in women with absent umbilical end-diastolic velocity. STUDY DESIGN: Absent umbilical end-diastolic velocity was detected in 88 women. Sixteen of them were prospectively followed up in their 19 subsequent pregnancies. These pregnancies were compared with their index pregnancies. RESULTS: The index pregnancy was invariably complicated with a perinatal mortality of 56%, growth restriction in 94% (15/16), and prematurity in 100% (75% < 32 weeks' gestation). In contrast, the outcome of the subsequent pregnancies was much better, and 74% (14/19) were uncomplicated. No perinatal deaths occurred, and none were delivered before 32 weeks' gestation. Absent umbilical end-diastolic velocity recurred in only two pregnancies, both of which were complicated. Six women had autoantibodies; these accounted for 80% (4/5) of subsequent complicated pregnancies. CONCLUSION: After an index pregnancy with absent umbilical end-diastolic velocity, subsequent pregnancies had favorable outcomes. Recurrence of absent umbilical end-diastolic velocity was low. The absence of autoantibodies and normal Doppler studies were associated with improved outcome. PMID- 8438945 TI - Maternal age and placenta previa: a population-based, case-control study. AB - OBJECTIVE: Our purpose was to determine if advanced maternal age has an adverse effect on placenta previa independent of other risk factors. STUDY DESIGN: A population-based, case-control study was performed with North Carolina vital records from 1988 to 1990, individually matching controls to cases on maternal race, gravidity, parity, previous spontaneous or induced abortion, previous cesarean section, and gestational age at delivery. RESULTS: A multivariate analysis showed that women aged 34 years or older had a two to three times higher risk of placenta previa in relation to women < 20 years old. A clear dose response pattern was observed with increasing age. CONCLUSION: Advancing maternal age appears to increase the risk of placenta previa independent of other factors. PMID- 8438946 TI - Placental and fetal Doppler velocimetry in pregnancies complicated by maternal diabetes mellitus. AB - OBJECTIVE: Our purpose was to investigate placental and fetal circulation in pregnancies complicated by maternal diabetes mellitus and to relate any changes to fetal blood pH, Po2, and hematocrit. STUDY DESIGN: Doppler measurements of both uterine arteries, one umbilical artery, the fetal descending thoracic aorta, and one fetal middle cerebral artery were performed in 65 well-controlled diabetic pregnancies in a cross-sectional study at the Harris Birthright Research Centre for Fetal Medicine, London. In 41 cases cordocentesis was also performed for the measurement of umbilical venous blood pH, Po2, and hematocrit. RESULTS: The mean umbilical venous blood pH was significantly lower and the hematocrit significantly higher than the appropriate normal mean for gestation. However, the Doppler indices of the placental and fetal circulations were essentially normal, except in some of the cases complicated by preeclampsia or intrauterine growth retardation. CONCLUSIONS: Maternal diabetes mellitus is not associated with abnormalities in Doppler indexes of the placental or fetal circulations. PMID- 8438947 TI - Secretion of prostanoids by platelets and monocytes in normal and hypertensive pregnancies. AB - OBJECTIVES: Secretory products of immune cells may induce or potentiate coagulation disturbances and vasoconstriction, both central features of pregnancy induced hypertension. Women with chronic essential hypertension are at high risk of superimposed pregnancy-induced hypertension. The aim of our study was to compare secretory rates of prostanoids (active in coagulation and vascular reactivity) by peripheral blood monocytes and platelets from nonpregnant controls and from women in the third trimester of pregnancy, normals and those with either pregnancy-induced hypertension or uncomplicated chronic essential hypertension. STUDY DESIGN: From 100 ml blood, peripheral blood monocytes and platelets were isolated; their relative rates of in vitro production of prostacyclin, prostaglandin E2, and thromboxane were measured, and responses to stimulation by arachidonic acid or the calcium ionophore A23187 were compared among the four groups of subjects. RESULTS: Basal peripheral blood monocyte secretory levels of prostanoids were low in all groups, with responses to both stimuli. Cells from women with chronic essential hypertension had a relatively exaggerated rise in thromboxane secretion (and to a lesser extent, prostacyclin) in response to the stimuli used, with a similar but less marked trend for those with pregnancy induced hypertension. Platelets from women with chronic essential hypertension had particularly high basal secretory levels of thromboxane, with little further response to stimulation by arachidonic acid or A23187. CONCLUSIONS: Our work demonstrates clearly for the first time that peripheral blood monocytes from pregnant women secrete low levels of vasoactive prostanoids and respond to the stimuli used in a manner similar to that of nonpregnant women, and that cells from pregnant women with hypertension have a tendency to increased reactivity that is most marked in those with chronic essential hypertension. Platelets from women with chronic essential hypertension secrete near-maximal amounts of thromboxane in the absence of exogenous stimuli, indicating a degree of prior activation. PMID- 8438948 TI - Pharmacokinetics of ampicillin and sulbactam in pregnancy. AB - OBJECTIVE: This study evaluated the effects pregnancy had on pharmacokinetic parameters of ampicillin and sulbactam. STUDY DESIGN: Twenty-two women undergoing cesarean section for obstetric indications were randomly assigned to receive a single intraoperative dose of either 1 gm of ampicillin intravenously or 1 gm of ampicillin plus 0.5 gm of sulbactam intravenously after umbilical cord clamping. Blood was drawn from an indwelling intravenous catheter at 15, 30, 45, 60, 120, 240, and 360 minutes after infusion of the antibiotic for determination of serum ampicillin and/or sulbactam levels. Pharmacokinetic parameters were determined by fitting data (serum concentrations versus time) to a single-compartment model that provided elimination rate constants, beta-intercept (calculated concentration at 0 minutes), area under the time-versus-concentration curve, half life of the drug, total body clearance, and volume of distribution. After the examination 6 weeks post partum, each subject was given an additional dose of the drug she had received during cesarean section, and a second pharmacokinetic study was performed and compared with the previous results. RESULTS: Pregnancy significantly increased the elimination rate constant, decreased the area under the drug-versus-time curve, shortened the serum half-life, and increased the total body clearance in comparison with these parameters in the nonpregnant state for ampicillin. Sulbactam kinetics were similarly affected, although these changes failed to attain statistical significance. CONCLUSION: Because pregnancy is associated with more rapid elimination of beta-lactam drugs, physicians treating infections in pregnant or newly parturient women should consider using shorter intervals between antibiotic doses when a range of dosage intervals is under consideration. PMID- 8438949 TI - Impact of medical treatment of endometriosis on bone mass. AB - A review of studies examining the effect of medical therapy of endometriosis on bone mass and potential approaches to preventing bone loss was undertaken. Studies specifically examining bone density in women with endometriosis treated medically were used. Reports on effects of oral contraceptives and progestins on bone mass were derived from women using them for contraception. Oral contraceptives and medroxyprogesterone acetate apparently did not adversely affect bone mass. While initial studies with dual-photon absorptiometry were unable to detect appreciable bone loss with gonadotropin-releasing hormone agonist, subsequent studies have invariably found significant bone loss beginning as early as 3 months of treatment. Quantitated computerized tomography always shows significant trabecular bone loss of the vertebrae and hip with gonadotropin releasing hormone agonist. Depot preparations appear to produce more marked loss than daily injections of intranasal spray. Recent studies indicate recovery of bone loss may take longer than 6 months or even 1 year after discontinuation of therapy with considerable individual variation. Danazol produced bone gain. Bone loss with gonadotropin-releasing hormone agonists could be prevented or attenuated with progestins, and this is worthy of further studies. Impact of medical therapy on bone mass should be a practical consideration in the selection of patients, in repeat medical therapy for recurrence of endometriosis, and in formulation of medical therapy so as to attenuate or overcome such silent adverse effects. PMID- 8438950 TI - Effect of administration route and estrogen manipulation on endometrial uptake of Photofrin porfimer sodium. AB - OBJECTIVE: Our purpose was to evaluate the influence of the route of drug administration and target tissue vascularity on the distribution of a photosensitizer, Photofrin porfimer sodium, in the uterus. STUDY DESIGN: The study was divided in two phases. In phase I 80 mature female rats were hormonally suppressed and then stimulated with estrogen. They were randomized to receive intravenous, intraperitoneal, or intrauterine Photofrin and killed 3, 6, 24, or 48 hours later. Drug distribution and levels were then determined. In phase II 40 female rats were randomized to receive hormonal stimulation, suppression, both, or neither. All received intrauterine Photofrin and were killed 24 hours later. Statistical analysis was performed with the unpaired t test and the two-way analysis of variance. RESULTS: Intrauterine administration was determined to be the simplest and most effective method of delivery because it provided for optimal uptake and distribution (p = 0.05) within the uterus, at lower doses. CONCLUSIONS: Selective localization of photosensitizer within the target tissue suggests that highly selective photodynamic destruction of endometrial tissue can be achieved. Furthermore, the combination of intrauterine administration of photosensitizer with estrogen adjuvant may minimize the most debilitating side effect of Photofrin, cutaneous phototoxicity. PMID- 8438951 TI - Enhanced proliferation of fetal rat hepatocytes in primary culture induced by ritodrine. AB - OBJECTIVE: Although ritodrine crosses the placenta, its direct effect on fetal cell proliferation has not been reported. We hypothesized that beta 2-adrenergic receptor stimulation could promote fetal liver growth. STUDY DESIGN: Ritodrine was added to serum- and hormone-free primary cultures of fetal, neonatal, or adult rat hepatocytes. We measured both tritiated thymidine incorporation into deoxyribonucleic acid and nucleus number. The effect of ritodrine on cell cycle was also analyzed with flow cytometry. RESULTS: Ritodrine enhanced the proliferation of fetal rat hepatocytes. Ritodrine remarkably stimulated deoxyribonucleic acid synthesis of fetal and neonatal but not adult hepatocytes. The effect was dose dependent and was antagonized by propranolol. Analysis of the nuclear deoxyribonucleic acid content derived from flow cytometry revealed that cells stimulated by ritodrine entered S phase. CONCLUSION: These results indicate that ritodrine may promote the proliferation of fetal hepatocytes through the stimulation of beta 2-adrenergic receptors, followed by induction of deoxyribonucleic acid synthesis. PMID- 8438952 TI - Interaction of myogenic and adrenergic mechanisms in isolated, pressurized uterine radial arteries from late-pregnant and nonpregnant rats. AB - OBJECTIVE: The purpose of this study was to examine how myogenic and adrenergic mechanisms interact in controlling the lumen diameter of small uterine arteries from nonpregnant and late-pregnant rats. STUDY DESIGN: Radial arteries (150 to 250 microns lumen diameter) from nonpregnant (n = 28) and late-pregnant (n = 18) rats were studied in vitro under conditions of varying transmural pressure and agonist concentrations. RESULTS: (1) Arteries from late-pregnant rats were significantly (p < 0.05) larger in diameter and, unlike nonpregnant vessels, developed a stable intrinsic tone at transmural pressures > 25 mm Hg. (2) Vessels from late-pregnant rats displayed a threefold increase in sensitivity to the constrictor effects of phenylephrine: 50% of maximal constriction, nonpregnant = 691 +/- 148 nmol/L and late-pregnant = 229 +/- 32 nmol/L (p < 0.01). (3) There was no difference in sensitivity to potassium depolarization. (4) Arteries from late-pregnant rats actively constricted to changes in transmural pressure, whereas those from nonpregnant did not unless preactivated beforehand with phenylephrine or K+. (5) After preconstriction the autoregulatory effectiveness of late-pregnant arteries in physiologic saline solution versus phenylephrine or K+, or of nonpregnant in K+ and phenylephrine, appeared to be equal in terms of absolute micrometers but not relative percent change in lumen diameter. CONCLUSION: Pregnancy is associated with significant changes in the active contractile properties of uterine resistance artery function, specifically heightened alpha-adrenergic sensitivity, intrinsic (pressure-dependent) tone, and myogenic reactivity. PMID- 8438953 TI - Effects of antipyrine on umbilical and regional metabolism in late gestation in the fetal lamb. AB - OBJECTIVE: Antipyrine has been used extensively in fetal metabolic studies and is now known to inhibit prostaglandin synthesis; therefore we wished to determine the effects of antipyrine on fetal umbilical and regional metabolism. STUDY DESIGN: Chronically catheterized fetal lambs were randomly assigned to antipyrine (n = 6) or control (n = 5) groups. Animals in the antipyrine group were infused with antipyrine (mean +/- SD 9.6 +/- 0.9 mg/min for 165 +/- 38 minutes), and control group animals were not infused. Measurements were made of fetal blood gases, oxygen content, glucose, lactate, lower-body blood flow, upper-body flow distribution, and substrate uptakes across the umbilical and hind limb circulations. The unpaired t test, correlation coefficient, and regression analysis were used for comparisons. RESULTS: There were no differences in antipyrine and control group animals with respect to blood gases, metabolite levels, umbilical blood flow, or umbilical uptakes. Hind limb blood flow (p < 0.10) and oxygen uptake (p < 0.05) were lower and lactate production was higher (p < 0.01) in antipyrine animals than in control group animals. Duration of antipyrine exposure correlated directly with hind limb lactate production (r = 0.85, p < 0.001) and inversely with hind limb oxygen uptake (r = -0.65, p < 0.05). The distribution of blood flow within the fetal upper body also differed between groups, with higher cardiac distribution in the antipyrine group (p < 0.025). CONCLUSIONS: Antipyrine does not affect umbilical metabolism but does affect carcass metabolism and fetal blood flow distribution. PMID- 8438954 TI - Endotoxin-induced fetal growth retardation in the pregnant guinea pig. AB - OBJECTIVES: Our purpose was to test the hypothesis that bacterial endotoxin may reduce fetal growth and to assess some of the pathophysiologic mechanisms of such an effect. STUDY DESIGN: Two randomly selected groups of nine guinea pigs at 30 days' gestation were treated with a solution of endotoxin isolated from Bacteroides fragilis or with solvent alone. Antibody titers, glucose, triglycerides, and 6-keto-prostaglandin F1 alpha were determined in maternal or fetal blood samples. Fetal weight was determined at 61 days' gestation. RESULTS: Endotoxin-treated guinea pigs showed positive antiendotoxin antibody titers, reduced weight gain, and significantly higher serum levels of triglycerides and 6 keto-prostaglandin F1 alpha, but not of glucose, than did sham-treated controls. Fetuses of endotoxin-treated animals had significantly lower birth weights and serum glucose concentrations and significantly higher triglyceride levels than did control fetuses. CONCLUSIONS: Bacteroides fragilis endotoxin causes fetal growth retardation in the pregnant guinea pig, which may be due to alterations in carbohydrate and fat metabolism mediated by cytokine action. PMID- 8438955 TI - Effects of repeated administration of cocaine to the fetal sheep in the last days of pregnancy. AB - OBJECTIVE: There are no reports on the direct effects of repeated cocaine administration to the fetus in late pregnancy. The aim of our study was therefore to examine the effects of repeated fetal exposure to cocaine on fetal development. STUDY DESIGN: Ten fetal sheep were instrumented at 123 +/- 1 days' gestation. Five fetuses received a single daily intravenous injection of cocaine (2 mg/kg) commencing at 130 to 131 days of gestation until delivery at 132 to 144 days of gestation; those fetuses were compared with fetuses that did not receive cocaine (n = 5). RESULTS: Basal fetal arterial blood gas values, blood pressure, heart rate, and nuchal and diaphragmatic activities did not change in the days preceding labor. Fetal arterial PO2 fell after cocaine administration, but this was significant only on the first day. Cocaine induced consistent significant alterations in fetal pH and PCO2, blood pressure, and heart rate. During labor cocaine stimulated diaphragmatic and nuchal muscle activity when compared with the other days. There was no increase in diaphragmatic and nuchal muscle activity in the controls. CONCLUSION: Our studies indicate that in fetal sheep the cardiovascular and blood gas response to cocaine in late pregnancy is not altered by repeated exposure to cocaine and that cocaine stimulates fetal breathing during labor. PMID- 8438956 TI - Total number of particles in a bounded region estimated directly with the nucleator: granulosa cell number in ovarian follicles. AB - OBJECTIVE: Our objective was to evaluate the precision of the "nucleator" with regard to estimation of the number of granulosa cells in individual follicles and the average number of granulosa cells per follicle in a group of follicles. STUDY DESIGN: Nine murine ovarian follicles embedded in plastic were oriented isotropically with the "orientator" by Mattfeldt, cut into 20 microns serial sections, and stained with hematoxylin. In each follicle the number of granulosa cells was estimated in two ways, both unbiased: (1) with the nucleator principle in the section that contains the nucleolus of the oocyte and (2) in the complete set of follicle sections with the "fractionator" principle. Estimates with the fractionator were interpreted as "true" values. Therefore the precision (CE) of the nucleator estimates could be calculated. RESULTS AND CONCLUSION: The nucleator provides precise estimates of the number of granulosa cells in one complete follicle: CE = 0.12. The amount of effort is minimal, because estimation is based on roughly 50 granulosa cells. The precision of the procedure with regard to estimation of the average number of granulosa cells in a group of follicles depends mainly on the biologic variation (CVbiol = 0.71). PMID- 8438957 TI - Intermittent sinusoidal heart rate pattern in vagotomized fetal lambs. AB - OBJECTIVES: Our aims were to investigate the relationship between the dose of arginine vasopressin and the pattern and duration of arginine vasopressin-induced sinusoidal fetal heart rate and to elucidate the correlation between intermittent sinusoidal heart rate and fetal sleep cycle. STUDY DESIGN: Sinusoidal heart rate pattern was induced by intravenous arginine vasopressin infusion at doses from 2 to 78 mlU/min into 11 chronically instrumented fetal lambs with bilateral cervical vagotomy. Appearance and frequency of sinusoidal heart rate, intermittent sinusoidal heart rate, and persistent sinusoidal heart rate were observed along with fetal tracheal pressure and electrooculogram. RESULTS: Intermittent sinusoidal heart rate response to low, medium, and high doses of arginine vasopressin appeared in 73.3%, 50.0%, and 33.3% of experiments, respectively. Intermittent sinusoidal heart rate appeared more frequently than persistent sinusoidal heart rate with lower doses (p < 0.02). When intermittent sinusoidal heart rate was induced, the incidence of sinusoidal patterns significantly increased during non-rapid-eye-movement sleep in comparison with rapid-eye-movement sleep (p < 0.01). CONCLUSIONS: Appearance of sinusoidal heart rate seems to be related to the dose of arginine vasopressin infused. Appearance of sinusoidal heart rate is also influenced by fetal sleep cycle; sinusoidal heart rate is more likely to appear during non-rapid-eye-movement sleep than during rapid-eye-movement sleep. These results support the hypothesis that persistent sinusoidal heart rate correlates with severity of stress. PMID- 8438958 TI - Surgical techniques for cytoreduction in advanced ovarian malignancy. PMID- 8438959 TI - Effect of fetal sepsis on umbilical cord blood gases. PMID- 8438960 TI - Abortion and obstetrics: a conflict of interests. PMID- 8438961 TI - Definition of pelvic abscess. PMID- 8438962 TI - Academic medicine and the workplace. PMID- 8438963 TI - Why don't medical students choose primary care? PMID- 8438964 TI - Primary health care and hospitalization: California and Cuba. PMID- 8438965 TI - Mental health services and outcome-driven health care. AB - Mental disorders and mental symptoms often go untreated in both chronic care and primary care settings. However, they covary with functional disability. They are likely to impair social and occupational function in medical outpatients and to cause excess instrumental and cognitive disability in frail older persons. In both groups, they are frequent and often remediable. The costs of untreated mental disorders are often shifted to caregivers and to society in general. To ensure adequate mental health care requires a reorientation of medical care toward optimizing function and well-being as well as longevity. Such a reorientation will necessarily entail more attention to treatable mental disorders. Research is needed to (1) develop firm knowledge on which to base integrated medical and mental health treatment and (2) evaluate the potential economic benefits of combined care. Incentives must be changed if such a paradigm of care is to prosper. PMID- 8438966 TI - The effect of federal grants on medical schools' production of primary care physicians. AB - OBJECTIVES: Title VII of the Health Professions Educational Assistance Act of 1976 was created to encourage the production of primary care physicians. This study explored recent trends in the proportion of US medical school graduates entering primary care in relationship to Title VII funding. METHODS: The American Medical Association Physician Masterfile was used to determine the specialty choice of all students graduating from American medical schools between 1960 and 1985. RESULTS: The proportion of graduates entering primary care rose from 19.7% in 1967 to 31.1% in 1976 and remained stable for the subsequent decade. The increase occurred before implementation of Title VII. Rural, state-owned medical schools with departments of family medicine tend to produce a greater proportion of primary care physicians than urban private schools without family medicine departments. CONCLUSIONS: The values of American medical schools and the reward structure of American medical practice favor the production of specialists over primary care physicians. Although Title VII helped to encourage and sustain the development of primary care educational programs at both the medical student and graduate levels, an increase in the proportion of primary care physicians will require fundamental changes. PMID- 8438967 TI - Commentary: primary care--medical students' unpopular choice. AB - Title VII funding to medical schools has not succeeded in correcting the shortage of primary care physicians. Although it is generally true that there is an inverse relationship between the amount of research funds awarded to a school and its success in producing primary care physicians, there are many exceptions. Neither Title VII, the amount of research funding, or Medicare's Direct Medical Education payments has had a substantial effect on the production of primary care physicians. These factors are comparatively insignificant when considered in the light of strong external incentives to specialize. Medical education cannot remedy the specialty imbalance unless the external environment becomes more friendly to generalists. PMID- 8438968 TI - Mental health service use by the elderly in nursing homes. AB - OBJECTIVES: Because current Omnibus Budget Reconciliation Act regulations influence the disposition of US nursing home residents who have mental illness, National Nursing Home Survey (1985) data are analyzed for predictors of mental health service use. METHODS: Elderly residents' rates of mental health service use are presented. Logistic regression yielded odds ratios for treatment by both mental health specialists and general practitioners for client and service system variables. RESULTS: Among the two thirds of elderly residents with a mental disorder (including dementia), only 4.5% receive any mental health treatment in a 1-month period. The ratio of specialist to general practitioner care is approximately 1:1. Patients seen by a specialist are likely to be younger (aged 65 to 74); live in the Northeast; and have a diagnosis of schizophrenia (13:1), dementia (3:1), or other mental disorders (5:1). Prior residence in a psychiatric hospital predicts care by both health professional types. Rural location, nonproprietary ownership of the nursing home, and aggressive behavior point to general physician care. CONCLUSIONS: Our findings indicate significant neglect of the mental health needs of older nursing home residents and underscore the importance of monitoring the regulations for screening and treatment of mental disorders under the Omnibus Budget Reconciliation Act. PMID- 8438969 TI - Expenditures in caring for patients with dementia who live at home. AB - OBJECTIVES: Given the national interest in progressive dementia, we estimated expenditures incurred in caring for dementia patients who live at home. METHODS: Primary caregivers of 264 patients from a university-based memory disorders clinic were interviewed at baseline and asked to keep service use diaries for 6 months; 141 caregivers who returned the diaries are the focus of this report. We examined both formal and informal services (distinguished by whether money was exchanged) and associated expenditures. RESULTS: Neither caregivers returning diaries nor their patients differed at baseline from those not returning diaries and their patients. Expenditures incurred over 6 months were extensive for both formal ($6986) and informal ($786) services. Out-of-pocket expenditures were high (e.g., in-home companion or sitter, adult day care, visiting nurse). Multivariable analyses indicated that patients with more severe symptoms of dementia and families with higher incomes reported significantly higher expenditures. CONCLUSIONS: The expense of caring for patients with progressive dementia living at home may be higher than previously estimated and frequently involves expenses paid directly by patients and their families. PMID- 8438970 TI - Reducing the use of physical restraints in nursing homes: will it increase costs? AB - OBJECTIVES: Reducing the widespread use of physical restraints in nursing homes is a primary goal of the federal nursing home reforms enacted as part of the Omnibus Budget Reconciliation Act of 1987. However, some nursing home operators assert that reducing restraint use could be prohibitively expensive, costing payors perhaps as much as $1 billion annually. We investigated whether nursing home residents free from physical restraint require more care and resources than similar residents who are restrained. METHODS: We examined the major component of nursing home costs--staff time--and its allocation among residents who were physically restrained and those who were not restrained. The multivariate analysis used staff-time-study data on the care of 11,932 nursing home residents in 276 facilities in seven states. RESULTS: The analyses indicate that, when differences in impairment and care needs are controlled for, residents who are physically restrained require more nursing care than other residents. Higher levels of nursing-assistant time were consistently provided to restrained residents. CONCLUSIONS: Residents free of restraints are less costly to care for than restrained residents. The 1987 federal requirements concerning restraint use, which are aimed at improving quality of care and quality of life, can be implemented without engendering a major increase in care costs. PMID- 8438971 TI - Medicare patients' use of overpriced procedures before and after the Omnibus Budget Reconciliation Act of 1987. AB - OBJECTIVES: Under the Omnibus Budget Reconciliation Act of 1987, Medicare reduced physician fees for 12 procedures identified as overprices. This paper describes trends in the use of these procedures and other physician services by Medicare patients during the 4-year period surrounding the implementation of the 1987 budget act. METHODS: Medicare physician claims files were used to develop trends in physician-services use from 1986 to 1989. Services were grouped into four categories: overpriced procedures, other surgery, medical care, and ancillary tests. RESULTS: Growth in the volume of overpriced procedures slowed substantially after the 1987 budget act was implemented. Moreover, the reduction in the rate of volume growth for these procedures differed little among specialities or areas. In comparison, the rate of volume growth fell modestly for other surgery, was unchanged for medical care, and increased for ancillary tests. CONCLUSIONS: Increases do not necessarily occur in the volume of surgical procedures whose Medicare fees are reduced. Although the conclusions that may be drawn from a descriptive analysis are limited, these findings suggest that concerns that the resource-based Medicare fee schedule will lead to higher surgery rates may be unwarranted. PMID- 8438972 TI - The cost-effectiveness of rehabilitation in the home: a study of Swedish elderly. AB - OBJECTIVES: To investigate whether care of elderly and disabled patients could be more cost-effective after a short-term hospital stay, we examined the impact of a primary home care intervention program on functional status, use and costs of care after 6 months. METHODS: When clinically ready for discharge from the hospital, chronically ill patients with dependence in one to five functions in personal activities of daily living were randomized to physician-led primary home care with a 24-hour service, and the controls were offered ordinary care. Physical, cognitive, social, and medical functions were assessed in 110 team subjects and 73 controls. Data regarding inpatient days and outpatient visits were collected and converted to costs. RESULTS: Team patients demonstrated better instrumental activities of daily living and outdoor walking and significantly fewer diagnoses and drugs at 6 months. They used less inpatient and more outpatient care compared with the control patients. Significant cost reductions were found in the team group. CONCLUSIONS: This primary home care intervention program is cost-effective, at least for a selection of patients at risk for long term hospital care. PMID- 8438973 TI - The underrecognition of HIV infection in women in an inner-city emergency room. AB - OBJECTIVES: This study analyzed the recognition of human immunodeficiency virus (HIV) infection and associated factors in women and men attending an emergency room in the Bronx, New York, NY. METHODS: From April 16, 1989, to May 5, 1989, the emergency room records of 2102 consecutive patients 13 years of age or older were reviewed and, for 856 patients undergoing venipuncture, linked anonymously to results of HIV antibody tested in excess blood. RESULTS: HIV seroprevalence was 7.8% in women and 14.6% in men. Among seropositive women, 5.0% had acquired immunodeficiency syndrome (AIDS), compared with 26.0% of men. Excluding patients with AIDS, HIV infection was recognized in 13.2% of women and 27.0% of men. HIV infection was recognized only in women aged 25 through 44 years. In men, recognition occurred in all age groups. Clinical presentation did not distinguish the seropositive from seronegative women. Risk assessments were recorded less frequently for women (11.2%) than men (15.9%). For 92.5% of persons with any behavioral risk assessment, injecting drug use was the only behavior assessed. CONCLUSIONS: HIV infection is underrecognized in women, in part, because of a lower prevalence of AIDS. Universal HIV risk assessment, which includes heterosexual behaviors, may help increase recognition of HIV in women and opportunities for early intervention. PMID- 8438974 TI - The underreporting of cocaine-related trauma: drug abuse warning network reports vs hospital toxicology tests. AB - OBJECTIVE: The purpose of this study was to assess whether cocaine-related trauma is underreported to the US Federal Drug Abuse Warning Network (DAWN). METHODS: We compared DAWN reports filed by an urban emergency department with the department's toxicology results for patients treated for major trauma. DAWN regulations in effect during the study period required the reporting of all patients treated for injury who used drugs or who tested positive for drugs of abuse. RESULTS: Of 520 patients treated for major trauma, 217 (42%) were tested for a variety of drugs. Of these, 82 (38%) tested positive for cocaine. Of the 102 patients injured in motor vehicle accidents, 20 (20%) tested positive for cocaine. Of the 59 patients injured in motor vehicle accidents who were under age 40, 18 (30%) tested positive for cocaine. Of 100 victims of violent assault, 57 tested positive for cocaine. During the time period studied, DAWN recorded 48 hospital visits associated with cocaine, none involving trauma or injury. CONCLUSIONS: Cocaine-related trauma was unreported to DAWN despite the hospital's compliance with the system's guidelines. The pattern of DAWN reports from other institutions suggests that underreporting of cocaine-related injury is widespread. PMID- 8438975 TI - Primary care and public emergency department overcrowding. AB - OBJECTIVES: Our objective was to evaluate whether referral to primary care settings would be clinically appropriate for and acceptable to patients waiting for emergency department care for nonemergency conditions. METHODS: We studied 700 patients waiting for emergency department care at a public hospital. Access to alternative sources of medical care, clinical appropriateness of emergency department use, and patients' willingness to use nonemergency services were measured and compared between patients with and without a regular source of care. RESULTS: Nearly half (45%) of the patients cited access barriers to primary care as their reason for using the emergency department. Only 13% of the patients waiting for care had conditions that were clinically appropriate for emergency department services. Patients with a regular source of care used the emergency department more appropriately than did patients without a regular source of care. Thirty-eight percent of the patients expressed a willingness to trade their emergency department visit for an appointment with a physician within 3 days. CONCLUSIONS: Public emergency departments could refer large numbers of patients to appointments at primary care facilities. This alternative would be viable only if the availability and coordination of primary care services were enhanced for low-income populations. PMID- 8438976 TI - Treating measles: the appropriateness of admission to a Wisconsin children's hospital. AB - OBJECTIVE: A large number of children with measles were hospitalized at a children's hospital during a metropolitan measles outbreak. In this study we addressed the appropriateness of those admissions. METHODS: Charts of all 634 patients with a diagnosis of measles who were treated between August 1989 and April 1990 were reviewed. Determination of the appropriateness of hospital admission was based on severity of illness and presence of severe complications of measles. RESULTS: Of 564 patients with clinical measles or serologic evidence of recent infection, 252 were inpatients (median age 1.5 years) and 312 were outpatients (median age 2.1 years). Fifty-nine (23.4%) of the inpatients had been inappropriately admitted. Inpatients were significantly more likely than outpatients to have physiologic instability or a clinical complication. Children 15 months of age or younger were more likely to be hospitalized, as were children evaluated in the first 3 months of the outbreak period, even if admission was not appropriate on the basis of physiologic instability or complications. CONCLUSIONS: Younger patients with measles and patients evaluated earlier in the epidemic were more likely to be admitted to the hospital even when admission was inappropriate as assessed by degree of physiologic instability or presence of complications. PMID- 8438977 TI - Depression, anxiety, and social disability show synchrony of change in primary care patients. AB - OBJECTIVES: The purposes of this study were to (1) characterize the social disability associated with the common psychiatric illnesses of primary care patients in terms of role dysfunction (self-care, family role, social role, occupational role) and (2) establish whether severity of psychiatric illness and disability level show synchrony of change. METHODS: A two-stage sample design was employed. In the first stage, 1994 consecutive attenders of 25 general practitioners were screened on psychiatric illness by their physicians and with the General Health Questionnaire. A stratified random sample (n = 285) with differing probabilities was selected for a second-stage interview. Patients with psychiatric symptoms were reinterviewed 1 and 3.5 years later (n = 143). RESULTS: (1) Disability level among patients was increased (moderately for depression, mildly for anxiety) and was associated with severity of psychiatric illness. (2) Most disability was found in occupational and social roles. (3) Change in severity of psychiatric illness was concordant with change in level of disability and was largely invariant across diagnosis (depression, anxiety, mixed anxiety/depression). At follow-up, disability among improved patients had returned to normal levels. CONCLUSIONS: Psychiatric illness in primary care patients is associated with mild to moderate disability, and severity of psychiatric illness and disability show synchrony of change. PMID- 8438978 TI - A work-site nutrition intervention: its effects on the consumption of cancer related nutrients. AB - OBJECTIVES: In a work-site nutrition intervention targeting fat and fiber, we examined the intervention's effect on specific nutrients implicated in carcinogenesis, including trace metals, vitamins, and categories of fatty acids. The rationale was based on the association observed in a variety of epidemiologic studies between these nutrients and epithelial cancers. METHODS: Data were taken from eight control companies and five intervention companies that fully implemented the Treatwell intervention. Analyses of variance were used preserving the study's nested design. RESULTS: Significant intervention-related associations were observed for increased total vitamin A and carotene. Marginal intervention effects were observed for relative decreases in the percentage of calories from both saturated and monounsaturated fatty acids, a relatively smaller increase in the percentage of calories from polyunsaturated fatty acids, and an increase in the consumption of vitamin B6. CONCLUSIONS: Results indicate a broader effect of the intervention than on fat and fiber only. Increased intake of carotene, the single most important of these other nutrients, is plausibly related to a variety of epithelial cancers. PMID- 8438980 TI - California adults with elevated blood lead levels, 1987 through 1990. AB - OBJECTIVES: Follow-up of California blood lead registry reports, 95% of which are of occupationally exposed adults, can guide interventions at specific high-risk work sites and measure the impact of targeted, industry-specific interventions. METHODS: A protocol was implemented to follow up the most severe case reports (> or = 2.90 mumol/L) and establish a statistical database for descriptive analysis. RESULTS: From 1987 through 1990, the California Department of Health Services received 17,951 reports for 4069 civilian, noninstitutionalized adults employed by at least 328 companies. Of 232 incident case subjects with severe lead toxicity (> or = 2.90 mumol/L), 182 were successfully traced and interviewed. Index case subjects were mostly male (95%) and disproportionately Hispanic (46%); 35% lived with children aged 7 or younger, and 10% had been hospitalized. Ninety four percent involved overexposures at work sites that lacked medical removal (50%), ventilation (36%), appropriate respirators (62%), training (64%), clothing changes (45%), or showering (60%). CONCLUSIONS: Well-known risk factors for occupational lead poisoning clustered at the work sites of index case subjects. Despite standards of the Occupational Safety and Health Administration, lead overexposure in California adults remains a significant public and occupational health concern. PMID- 8438979 TI - The Healthy Worker Project: a work-site intervention for weight control and smoking cessation. AB - OBJECTIVES: A randomized trial was conducted to evaluate the effectiveness of a work-site health promotion program in reducing obesity and the prevalence of cigarette smoking. METHODS: Thirty-two work sites were randomized to treatment or no treatment for 2 years. Treatment consisted of health education classes combined with a payroll-based incentive system. Evaluation was based on cohort and cross-sectional surveys. RESULTS: Of 10,000 total employees in treatment work sites, 2041 and 270 participated in weight control and smoking cessation programs, respectively. Weight losses averaged 4.8 lbs, and 43% of smoking participants quit. Net 2-year reductions in smoking prevalence in treatment vs control work sites were 4.0% and 2.1% in cross-sectional and cohort surveys, respectively. No treatment effect was found for weight. Treatment effects for smoking prevalence and weight were both positively correlated with participation rates in the intervention programs (r = .45 for smoking and r = .55 for weight). CONCLUSIONS: This work-site health promotion program was effective in reducing smoking prevalence at a cost that is believed to make the investment worthwhile. PMID- 8438981 TI - The initial impact of a workplace lead-poisoning prevention project. AB - The California Department of Health Services began an occupational lead poisoning prevention project in cooperation with 275 radiator service companies. The agency developed and marketed resources to facilitate companies' own efforts, tracked the progress of each company, and urged the companies to conduct blood lead testing. Testing by participating employers increased from 9% to 95%, and 10 times as many companies with likely overexposures were identified as had been reported to the state's lead registry in the previous year. The success of this project indicates that the model should be applied more extensively. PMID- 8438982 TI - Is access to home health care a problem in rural areas? AB - In 1987, urban Medicare beneficiaries were 13.7% more likely than their rural counterparts to use Medicare home health care services. Regression analysis shows that rural use rates, particularly those in sparsely populated areas, fall short of those in urban areas, other things being equal. Rural areas have lower Medicare ceilings, proportionately fewer visiting nurse associations, and lower availability of auxiliary services. These factors combined account for 82% of the difference between rural and urban use rates. PMID- 8438983 TI - The smoking habits of Minnesota physicians. AB - The prevalence of smoking among physicians has gradually declined over the past 25 years. Few recent studies have examined specific smoking habits. Of 393 physicians in the Minnesota Medical Association who responded to a survey (response rate of 83%), 9% reported smoking any form of tobacco. The prevalence of cigarette smoking was 4.9%, while 5.1% smoked a pipe and 2.1% smoked cigars. The prevalence estimates of current and former smokers were greater among men than women and among older than younger physicians. Cigarette and overall smoking prevalence among physicians continues to be well below levels reported for the general population. PMID- 8438984 TI - Health as a human right: an epidemiologist's perspective on the public health. AB - The modern idea of health as a human right is examined, as it evolved from the 18th century, in terms of its origins, its essential content, and 20th-century attempts at implementation. Equity for social groups is seen as a guiding principle. Two attempts at implementation, in Britain and in Cuba, are examined for their effects on equity in health service and in health states. The British National Health Service achieved equity between social classes in services but failed to achieve it in health states (as measured by mortality). Deficiencies in commitment to public health services, it is argued, contributed largely to this failure. The Cuban experiment appears to have moved beyond equity solely in services and toward equity in health states. This success reflects an overall Cuban commitment to the public health. Two important elements of that commitment are, first, continuous evaluation with flexible response and, second, community involvement. PMID- 8438985 TI - Seat belt study conclusions go beyond data. PMID- 8438986 TI - How accurate is the Reflotron cholesterol analyzer? 1. Accuracy of reflotron misrepresented in study. PMID- 8438987 TI - How accurate is the Reflotron cholesterol analyzer? 2. Reflotron screenings considered a success. PMID- 8438988 TI - Can smoking be child abuse? PMID- 8438989 TI - Underscoring the continued need for a sustained national HIV prevention and public education initiative. PMID- 8438990 TI - Human sexual behavior research. PMID- 8438991 TI - Domestic violence. PMID- 8438992 TI - The health of refugees and displaced persons: a public health priority. PMID- 8438993 TI - Advertising and promotion of alcohol and tobacco products to youth. PMID- 8438994 TI - Prevention of infections following penetrating abdominal trauma. AB - A major problem for patients who survive a traumatic injury is morbidity due to infectious complications; this risk increases when there is injury to the liver, pancreas, or colon, the abdominal trauma index is > 25, and/or surgery is prolonged. For major injuries of either the liver or pancreas, the use of closed suction drainage decreases the risk of infection; sump drainage should be avoided. Most penetrating colon injuries can be managed with primary repair or resection and anastomosis, unless there is an underlying medical condition or a need for massive transfusions. For gunshot wounds penetrating the colon, removal of retained missiles should be attempted because these increase the risk of abscess. A brief course of appropriate antibiotic treatment should be initiated as soon as possible after wounding and should be continued for 24 hours. Prolonged courses of antibiotic provide no added benefits. PMID- 8438995 TI - Factors influencing the risk of infection after trauma. AB - Infection after injury is characterized by the degree of contamination, the duration of attendant hypotension, and the delay in definitive surgical treatment. Factors further influencing this outcome include the age of the patient and, in most U.S. urban centers, the general health of the patient. Current antibiotic treatment of such patients may soon be assisted by selective and sequential immunostimulants, which are increasingly more specific for defined defects in host defenses after injury. An ever more significant contribution to morbidity and mortality on trauma services is pneumonia, which is often caused by gram-negative aerobes. The design of clinically significant trials with respect to infection in the injury patient will be more difficult and complex. PMID- 8438996 TI - Role of immunomodulator therapy in sepsis. AB - Endotoxin is released from the cell walls of gram-negative bacteria and causes severe systemic effects due to the release of cytokines. Monoclonal antibodies directed at endotoxin may be promising adjuncts to the standard therapeutic interventions of antibiotics and supportive measures used to treat patients with gram-negative sepsis. Monoclonal antibodies interfere with the bacteria's ability to trigger an unfavorable response. In recent clinical trials, two immunoglobulin M monoclonal antibodies have improved survival in certain small patient subgroups, although neither drug improved overall mortality in all septic patients treated. E5 murine monoclonal antibody reduced mortality in patients with gram-negative sepsis who were not in refractory shock. HA-1A human monoclonal antibody reduced mortality in patients with gram-negative infections who were bacteremic or in shock. The statistical significance and clinical importance of these benefits is not yet known. Results of these clinical trials are reviewed. PMID- 8438997 TI - Occupational risks of infection in the surgical management of trauma patients. AB - The evolution of the acquired immunodeficiency syndrome secondary to the human immunodeficiency virus (HIV) has resulted in increased concern by surgeons and other members of the health care team with respect to occupationally acquired viral infections. Hepatitis B, hepatitis C, and other viral infections of the liver remain more important than HIV as a cause of morbidity and death for surgeons. Reduction in risk of these infections for surgeons can be achieved by hepatitis B vaccination, better utilization of personal protective equipment, and by improved techniques in the performance of procedures. An overall enhanced awareness in the use of sharp instruments in the operating room is most important. Finally, serologic testing of patients prior to operative procedures, or of surgeons as a condition to performing procedures is an expensive and counterproductive exercise that cannot be recommended. PMID- 8438998 TI - Hospital-acquired gram-negative pneumonia in critically ill, injured patients. AB - Hospital-acquired gram-negative pneumonia is a major problem in critically ill, injured patients. The currently available therapeutic interventions to prevent the disease process are of limited usefulness. This most likely reflects an incomplete understanding of the complex pathophysiologic mechanism and thus invites examination of alternative mechanisms. We have hypothesized that the lung's response to traumatic injury may be driving the local organ injury by generating an early, local pulmonary cytokine production independent of the systemic cytokine response or the intensive care unit environment. Understanding the local pulmonary cytokine response to traumatic injury and its effect on the pulmonary airspace's immunologic contents may yield targeted and clinically relevant therapeutic interventions. Currently, the successful treatment of hospital-acquired gram-negative pneumonia depends on a clear and consistent definition of the disease process, knowledge that therapy with a single antibiotic is effective, and use of a concise treatment protocol that provides for reassessment of the patient when antibiotic therapy appears to be ineffective. PMID- 8438999 TI - Injury severity scoring: perspectives in development and future directions. AB - The impulse to catalogue injuries is as old as human history, but the actual measurement of injury severity began only 40 years ago. The rapid development of objective measures for trauma required enormous investments of time and money to accrue large enough data bases to validate these measures. Tools are now available to measure both physical injury (injury severity score) and physiologic injury (revised trauma score), as well as their synergistic combination into the probability of survival score, and these tools are in everyday use at most trauma centers. Nevertheless, it is likely that further improvement in outcome prediction is possible. The current injury severity scoring system is based on clinically assigned injury severity rather than measured outcome, and considers only one injury per body region. Both of these shortcomings should be addressed. The advent of large computerized data bases will facilitate this process. PMID- 8439000 TI - Predicting infectious morbidity in elective operations. AB - The determination of surgical risk is a major problem in general surgical practice and many studies have attempted to predict postoperative outcome. Clinical judgment is still a fundamental skill with which the experienced surgeon can estimate the risk of postoperative infectious morbidity. Predictive scores based on statistical analysis have also proven to be valid and useful tools. This discussion analyzes the importance of surgical risk prediction. With future research in this area, it is hoped that therapeutic strategies will result that will reduce or eliminate this risk. PMID- 8439001 TI - Mechanism of increased susceptibility to infection following hemorrhage. AB - Although hemorrhage is known to cause increased susceptibility to infection, the precise mechanism remains unknown. Regional hypoxia due to reduced blood flow following hemorrhage appears to be a primary mediator that initiates the cascade of events leading to immunodepression and increased susceptibility to infection. This was evident from depression of lymphocyte functions, production of various lymphokines, macrophage expression of receptors involved in opsonin-mediated phagocytosis, and antigen presentation function of peritoneal, splenic, and Kupffer cells following hemorrhage. The depression in various immune functions is apparent immediately after hemorrhage and persists for a prolonged period of time, despite volume resuscitation. Furthermore, it appears that the increased release of systemic mediators, such as interleukin-1 (IL-1), IL-6, tumor necrosis factor, transforming growth factor type beta, and prostaglandin E2 is associated with marked depression in immune responses and increased susceptibility to infection following hemorrhage. PMID- 8439002 TI - Nutritional support in the patient with the systemic inflammatory response syndrome. AB - The syndrome previously known as "sepsis" is now recognized as a generalized response to a number of stimuli that cause systemic activation of inflammatory mediators. The so-called "systemic inflammatory response syndrome" (SIRS) represents a final common endpoint to overwhelming persistent infection, massive tissue injury, prolonged tissue oxygen debt, or any other insult precipitating global inflammation. The metabolic consequences of SIRS are profound but in the past were not fully appreciated because patients died from more immediate causes (e.g., renal failure, pulmonary failure, gastrointestinal hemorrhage). As modern critical care has maintained patients in prolonged phases of recovery, the need for appreciation of the nutritional impact of the hypermetabolic response is taking center stage. The systemic activation of counterregulatory hormones, cytokines, and other mediators of inflammation has complex metabolic effects that are discussed in this review. A rational approach to assessing nutritional needs in patients with SIRS will be presented along with a discussion of how the needs are best met. Finally, the pitfalls encountered in nutritional support of patients with sepsis will be outlined along with a protocol for monitoring tolerance to and effectiveness of metabolic support in SIRS. PMID- 8439003 TI - The human leukocyte antigens and their relationship to infection. AB - Human leukocyte antigen DR (HLA-DR) expression on peripheral blood monocytes has been found to correlate highly with infection in many clinical scenarios. This is particularly true for the trauma patient, where changes in HLA-DR expression predate and therefore often predict development of infection. Expression of this antigen is limited to immunocompetent cells, such as B lymphocytes, macrophages, and activated T cells. The HLA-DR heterodimer is required for major histocompatibility complex restricted antigen presentation, a key step in the development of a specific immune response. The degree of monocyte HLA-DR expression may reflect the ability eventually to present antigen, since close correlation has been found between the two. There was remarkable reproducibility of monocyte HLA-DR expression among > 100 asymptomatic volunteers without regard to age, gender, race, and sampling time. Immunosuppressive medication had no effect. Incubation of monocytes from severely infected patients with endotoxin distinguished survivors from those who died by enhanced HLA-DR expression in the survivors. Of several agents that enhance HLA-DR expression, interferon-gamma has received the most attention in experimental models as well as humans. Although promising in selected patients, further clinical trials will be needed to define its specific role. Identification of the patient at high risk for infection, particularly following trauma, will be crucial for the efficient evaluation of future therapeutic interventions. Monocyte HLA-DR expression is the first simple assessment of the host immune response to play an important role in this endeavor. PMID- 8439004 TI - Management of the surgical patient with multiple system organ failure. AB - The management of the surgical patient with multiple system organ failure (MSOF) remains a formidable problem. Despite advances in critical care, mortality from MSOF remains virtually unchanged since the syndrome was characterized almost two decades ago. At the present time, there are no modalities that can actively reverse established organ failure, hence the treatment of these patients consists of metabolic and hemodynamic support until the process reverses itself or until death. Therefore, the best management of the surgical patient at risk for MSOF is prevention of the syndrome. Strategies to avoid MSOF include early institution of enteral nutrition, the use of specific nutritional substrates and formulas, early fixation of long bone fractures, prompt restoration of perfusion and oxygen delivery, and the aggressive diagnosis and drainage of abdominal infection prior to organ failure. This review will focus on oxygen delivery, early stabilization of fractures, and prompt reexploration for suspected abdominal sepsis. (Nutritional therapy is discussed in another article in this supplement.) All of these interventions have been associated with the prevention of MSOF and decreased mortality. In addition, future therapy using cytokines and monoclonal antibodies targeted for the prevention and treatment of MSOF will be examined. PMID- 8439005 TI - Combination antibiotic therapy in the management of intra-abdominal infection. AB - Combination antimicrobial regimens consisting of an agent with activity against gram-negative bacilli (an aminoglycoside) plus an agent with anaerobic activity (usually clindamycin or metronidazole) have traditionally been accepted as the standards for the treatment of intra-abdominal infection. Because of the problems of nephrotoxicity and ototoxicity in patients treated with aminoglycosides, clinical trials have been conducted using alternative combination therapy (e.g., aztreonam plus clindamycin) or single beta-lactam antimicrobial agents. Most clinical trials of intra-abdominal infections have been conducted in relatively small patient populations with a variety of low- and high-risk patients. The newer regimens have demonstrated efficacy equivalent to traditional combination therapy in selected patient populations. When selecting an antimicrobial regimen for treatment of intra-abdominal infection, multiple issues should be considered, including demonstrated efficacy in clinical trials, potential for adverse effects, and cost. PMID- 8439006 TI - UV resonance Raman spectroscopy for analytical, physical, and biophysical chemistry. Part 2. PMID- 8439007 TI - Marie Curie. Half-life of a legend. PMID- 8439008 TI - Ascorbate and dehydroascorbate measurements in aqueous solutions and plasma determined by gas chromatography-mass spectrometry. AB - The tert-butyldlmethylsllyl derivatives of ascorbic acid and dehydroascorbic acid were characterized by gas chromatography-mass spectrometry, and an isotope dilution assay for ascorbate and dehydroascorbate was developed using [13C6]ascorbic acid and [13C6]- and [6,6-2H2]dehydroascorbate. This assay was used to monitor ascorbic acid loss and the resulting rise of dehydroascorbic acid in aqueous solutions and plasma. Ascorbic acid was shown to rapidly decompose in aqueous solutions containing transition metal ions or when exposed to oxygen. Ethylenedlaminetetraacetic acid chelation did not prevent ascorbic acid degradation in aqueous solution, and ascorbate in ethylenedlaminetetraacetic acid chelated plasma was converted to dehydroascorbate on freezing. Gas chromatography mass spectrometry appears to be a satisfactory method for determining the ascorbate and dehydroascorbate content of solutions including human blood plasma, whether or not there is ongoing oxidation of ascorbate in those solutions. PMID- 8439009 TI - Na+/D-glucose cotransporter based bilayer lipid membrane sensor for D-glucose. AB - A new type of amperometric blosensor for glucose was fabricated using a Na+/D glucose cotransporter as the signal-transducing sensory element that exploits the D-glucose-triggered Na+ ion current through bilayer lipid membranes (BLMs). The planar BLM was formed by the folding method across a small aperture of a thin Teflon film. The Na+/D-glucose cotransporter, isolated and purified from small intestinal brush border membrane of guinea pigs, was embedded into BLMs through proteoliposomes. The number of the protein molecules thus incorporated in the present sensing membrane was estimated to be ca. 10(7). The sensor response was measured as an ionic current through the BLM arising from cotransported Na+ ion flux under a constant applied potential and was only induced by D-glucose above 10(-9) M, but not by the other monosaccharides except for D-galactose. The effect of applied potentials, Na+ and K+ ion concentrations, and the addition of a competitive inhibitor, phlorizin, were scrutinized to characterize the sensor output. The results were briefly discussed in terms of the potential use of the Na+/D-glucose cotransporter as a sensory element for D-glucose. PMID- 8439010 TI - Toxin detection using a tyrosinase-coupled oxygen electrode. AB - An enzyme-based "electrochemical canary" is described for the detection of cyanide. The sensing system imitates cyanide's site of toxicity in the mitochondria. The terminal sequence of electron transfer in aerobic respiration is mimicked by mediator coupling of tyrosinase catalysis to an electro-chemical system. An enzyme-coupled oxygen electrode is created which is sensitive to selective poisoning. Biocatalytic reduction of oxygen is promoted by electrochemically supplying tyrosinase with electrons. Thus, ferrocyanide is generated at a cathode and mediates the enzymatic reduction of oxygen to water. An enzyme-dependent reductive current can be monitored which is inhibited by cyanide in a concentration-dependent manner. Oxygen depletion in the reaction layer can be minimized by addressing enzyme activity using a potential pulsing routine. Enzyme activity is electrochemically initiated and terminated and the sensor becomes capable of continuous monitoring. Cyanide poisoning of the biological component is reversible, and it can be reused after rinsing. The resulting sensor detects cyanide based on its biological activity rather than its physical or chemical properties. PMID- 8439011 TI - Analyses of cryogenic samples using ion-induced desorption and multiphoton resonance ionization. AB - In this study, ion-beam-induced desorption with multiphoton resonance ionization detection of desorbed neutral molecules is used to characterize frozen aqueous solutions. This type of matrix is of particular importance since it serves as a model for biological matrices. The time-of-flight mass spectrum, obtained in this way for a millimolar tryptophan/H2O solution, is virtually identical to that for a submonolayer of tryptophan on a silicon wafer. The tryptophan signal from a frozen solution is demonstrated to have a linear dependence on concentration by using 4,4'-biphenyldiol as an internal standard. A detection limit of 2 x 10(-6) M is also demonstrated. Since our ion beam samples one layer of 0.1 cm2 and we assume 10(15) molecules/cm2 of ice, this concentration corresponds to approximately 4 x 10(6) molecules/layer. It is also shown that the signal exhibits an exponential decay with primary ion dose due to the accumulation of primary ion damage in the near-surface molecules. PMID- 8439012 TI - Observation of "hook effects" in the inhibition and dose-response curves of biotin assays based on the interaction of biotinylated glucose oxidase with (strept)avidin. AB - The inhibition of highly biotinylated enzymes by avidin and streptavidin has been used in the development of homogeneous assays for biotin and other analytes. Usually, this inhibition occurs in a similar fashion for both avidin and streptavidin. Specifically, the curves that relate the inhibition of the enzymatic activity with the concentration of avidin or streptavidin have a sigmoidal shape; I.e., the inhibition of the enzyme-biotin conjugates increases gradually with increasing amounts of avidin or streptavidin and arrives at a plateau at high binding protein concentrations. However, when these two biotin specific binding proteins interact with biotinylated glucose oxidase a significant difference in their inhibitory action is observed. In particular, the inhibition curves have a sigmoidal shape for streptavidin, while those for avidin exhibit a maximum ("hook") at low avidin concentrations. This difference in the reactivity of the two proteins with biotinylated enzymes influences both the shape of the dose-response curve and the detection limits of homogeneous enzyme linked competitive binding assays for biotin. PMID- 8439013 TI - Detection of electrophore-labeled DNA and albumin by gas chromatography: labile amide electrophoric release tags. PMID- 8439014 TI - To help the dying die--a new duty for anesthesiologists? PMID- 8439015 TI - A practice parameters overview. PMID- 8439016 TI - Epidural sufentanil and bupivacaine for labor analgesia and Doppler velocimetry of the umbilical and uterine arteries. AB - BACKGROUND: The pain of parturition is associated with major physiologic alterations mediated by neurohumoral factors and increased activation of the sympathetic nervous system. Epidural local anesthetics abolish or alleviate many of the pain-mediated responses by reducing maternal catecholamine levels, inducing sympathectomy and consequent vasodilatation. The hormone response to surgical stress is not attenuated after epidural opioids as efficiently as after local anesthetics. Opioid receptors may modulate sympathetic outflow at a spinal level. This study was performed to compare the effects of epidural sufentanil and bupivacaine on the uterine and placental circulation. METHODS: Utilizing a prospective randomized, double-blind study design, 30 healthy women at term were examined employing a color Doppler technique to assess and compare the effects of analgesia using sufentanil or bupivacaine epidurally during the first stage of labor on blood flow velocity waveforms in the uterine and umbilical arteries. RESULTS: Effective analgesia was provided by both drugs, bupivacaine and sufentanil. Uterine and umbilical blood velocity waveform indices did not change significantly. There was, however, a significantly greater incidence of fetuses with changes in heart rate tracings in the sufentanil group, decreased variability being the most frequent. Maternal side effects attributable to sufentanil were common but mild. No patient became hypotensive in either group. CONCLUSIONS: Epidural sufentanil and bupivacaine provide effective analgesia with acceptable side effects during the first stage of labor in healthy parturients. Neither drug had any detrimental effects on blood flow indexes reflecting peripheral vascular resistance in the umbilical and uterine arteries in healthy parturients. PMID- 8439017 TI - Indirect memory during anesthesia. The effect of midazolam. AB - BACKGROUND: The preservation of implicit memory function during anesthesia is controversial, with conflicting results appearing in the literature. This study was designed to elucidate the effect of midazolam as part of an anesthetic technique on implicit memory function during anesthesia. Using a prospective randomized, double-blind study design, performance in three tasks (category generation, free association, and homophone spelling) was assessed. METHODS: Forty-eight consenting patients were assigned to two equal groups, to receive 2 mg intravenous midazolam or normal saline before induction of anesthesia. Anesthesia was induced with fentanyl and propofol and maintained with isoflurane 1.3 MAC until incision and isoflurane 1.0 MAC in 70% nitrous oxide thereafter. Fentanyl was used for supplementation of anesthesia. During anesthesia, one of two 50-min tapes containing the test material was played to each patient on a portable cassette player. In the postanesthesia care unit and 48 h after surgery, patients were engaged in three tasks by an observer unaware of the treatment group or tape. RESULTS: No significant main effect of priming or midazolam was observed in any of the tasks. In the word-association task, an interaction was observed between priming and treatment group (F = 9.62, P < .01) due to negative priming in the placebo group. CONCLUSIONS: The lack of a main effect of priming in any of the three tasks is consistent with the conclusion that indirect memory was not demonstrated for events occurring during the standard anesthetic conditions of this study. Further, midazolam appeared to have no effect. PMID- 8439018 TI - The pressure rate quotient is not an indicator of myocardial ischemia in humans. An echocardiographic evaluation. AB - BACKGROUND: The pressure rate quotient (PRQ; mean arterial pressure/heart rate [MAP/HR]) less than one (PRQ < 1) has been proposed as a simple, clinically available hemodynamic index of myocardial ischemia. Recent investigations using electrocardiography (ECG) detection of myocardial ischemia have not found this index reliable. We prospectively compared PRQ < 1 to detection of myocardial ischemia via transesophageal echocardiography (TEE) and ECG in patients undergoing elective coronary artery bypass graft. METHODS: Forty-six of 50 patients admitted into the study had acceptable data acquisition. Calibrated ECG leads II and V5 were recorded with a computerized ST-segment analyzer. Hemodynamic data were stored at 2-min intervals. After tracheal intubation, a 5.0 MHz TEE probe was inserted. Electrocardiography-detected ischemia was defined as new onset ST-segment deviation (> or = 1 mm) lasting for > 1 min. Transesophageal echocardiography determination of ischemia was worsening of wall motion > or = 1 grade and lasting > 1 min. PRQ < 1 was compared to ECG and/or TEE as a predictor or indicator of myocardial ischemia. RESULTS: Electrocardiography ischemia occurred during 230 intervals in 10 patients, and in only 41 of 230 (18%) was PRQ < 1. Transesophageal echocardiography-defined ischemia occurred during 592 intervals in 9 patients, and in 119 of 592 (20%) PRQ < 1. Compared to ECG and TEE, PRQ < 1 had a low sensitivity (21%) and poor positive predictive value (25%). CONCLUSIONS: Pressure rate quotient < 1 is an unreliable indicator and predictor of myocardial ischemia when evaluated by ECG, TEE, and the combination of these modalities in patients undergoing coronary artery bypass graft surgery. PMID- 8439019 TI - Effect of posture on lung and regional chest wall mechanics. AB - BACKGROUND: Little is known about the extent to which changes in postures in clinical situations affect respiratory mechanics, even in humans with healthy respiratory systems. This study tested the hypothesis that posture has only small effects on overall respiratory system mechanics in healthy subjects, despite changes in parts of the respiratory system in some postures. METHODS: Measurements were made of airway flow, airway and esophageal pressures, and rib cage and abdominal volume displacements (with inductance plethysmography) of awake, healthy subjects, relaxed at functional residual capacity, during external forcing at 0.2 Hz with a tidal volume of 8-10 ml/kg. From these measurements, discrete Fourier transform was used to calculate elastances (E) and resistances (R) of the total respiratory system, lungs, total chest wall, and compartments of the chest wall (rib cage, diaphragm-abdomen, and belly wall). Measurements were made while the subjects were in nine different postures: in six of these, the torso was straight; in three, the torso was bent or twisted. RESULTS: Although changes in mechanics of parts of the respiratory system were evident in certain postures, overall respiratory mechanics were not greatly affected by posture. Changing from sitting to supine decreased E and R of the diaphragm-abdomen about 50% (P < .05), but total chest wall E and R changed only slightly. Lung E increased 24% (P < .05), but total respiratory E did not change (P < .05). Lung and total respiratory R increased 40-50% (P < .05) with this same change in posture. As long as the torso was straight, however, changes in orientation of 30 degrees from the horizontal or a shift to lateral posture resulted in only minor changes in the variables measured. Postures in which the torso was twisted or bent increased E of the total chest wall 20-30% compared to supine (P < .05), due to increases in E of one or more compartments. Respiratory system E also increased, at most 14%. Although lung R decreased 30-45% (P < .05) in these postures compared to supine with a straight torso, chest wall and total respiratory R generally were unchanged. CONCLUSIONS: Changes in respiratory system mechanics over a wide range of postures that may be encountered clinically are relatively small in healthy awake subjects due to adaptability of total chest wall mechanical behavior. PMID- 8439020 TI - Sufentanil disposition. Is it affected by erythromycin administration? AB - BACKGROUND: Because oral erythromycin administration has been associated with reduced elimination of alfentanil, suspicion has been raised about related opioids with similar metabolic pathways. A controlled crossover study of sufentanil pharmacokinetics was undertaken to resolve this issue. METHODS: Six subjects had measurements of plasma concentrations for 9 h after intravenous administration of sufentanil (3 micrograms/kg). Each subject was studied following no erythromycin (control) and after 1- and 7-day courses of erythromycin base. RESULTS: Plasma concentrations during the 9 h of measurement were similar before and after erythromycin. Terminal half-life and clearance and distribution volume did not change significantly among treatment groups. Values measured after 7 days of erythromycin were similar to controls. CONCLUSIONS: Prior administration of erythromycin does not alter pharmacokinetics of sufentanil in the 9 h following sufentanil administration. Thus, there are no apparent clinical consequences of prior or concomitant erythromycin administration in patients receiving sufentanil for procedures of 9 h or less. PMID- 8439021 TI - Increases in hemodynamic variables and catecholamine levels after rapid increase in isoflurane concentration. AB - BACKGROUND: Ventilation of the lungs with isoflurane in nitrous oxide and oxygen has been shown to increase the plasma concentration of norepinephrine. Whether this increase is related to the tachycardia and increased arterial blood pressures, seen following a sudden increase in the concentration of isoflurane, was tested in humans. METHODS: Twenty-two healthy patients in whom the trachea was intubated were given 15 min of stable isoflurane-O2-air anesthesia [end-tidal concentration of isoflurane (ETIso) of 1.3%] (baseline). Patients were then randomly allocated to one of two groups. For 13 "IsoHigh" patients, the inspired concentration of isoflurane was increased abruptly. In those patients, the ETIso was kept at 2.6% for 10 min, i.e., until the end of the study, after which the depth of anesthesia was reduced. For nine "IsoLow" control patients, the ETIso level of 1.3% was continued until the end of the study. Heart rate, arterial pressures, catecholamine levels, and end-tidal concentration of CO2 were recorded at baseline and at 1, 1.5, 2, 4, 6, and 10 min after increase in isoflurane. RESULTS: IsoHigh patients showed significant increases in heart rate (40% from 84.6 to 118.1 beats/min), systolic arterial pressure (SAP, 23%, from 96.4 to 118.3 mmHg), and diastolic arterial pressure (DAP, 30%, from 53.9 to 70.0 mmHg); all three variables peaked at 2 min. Significant increases occurred also in norepinephrine levels (80%, from 0.342 to 0.615 ng/ml) and in end-tidal concentration of CO2 (from 4.22% to 4.43%), both of which peaked at 4 min. Epinephrine levels did not increase significantly, although significant differences were seen between IsoHigh and IsoLow patients during the trial. IsoLow patients had no changes in these variables. CONCLUSIONS: A sudden increase in isoflurane concentration is associated with a transient but clinically significant increase in heart rate, arterial pressures, and norepinephrine concentration. PMID- 8439022 TI - Menstruation increases the risk of nausea and vomiting after laparoscopy. A prospective randomized study. AB - BACKGROUND: Several factors may influence the incidences of postoperative nausea and vomiting. In women, one of these factors may be the timing of their surgery in relation to their menstrual cycle. The purpose of this study was to assess the effect of menstruation and efficacy of the antiemetic droperidol on postoperative nausea and vomiting. METHODS: In a prospective randomized double-blind clinical trial, 100 female patients who were scheduled for laparoscopic tubal sterilization were stratified on the basis of the date of their last menses into menstrual (days 1-8) and nonmenstrual (days 9-28) groups. Patients in both groups were then randomized to receive placebo or 10, 20, or 30 micrograms/kg droperidol before induction of anesthesia, and data were obtained for 24 h after completion of their surgery. RESULTS: Nausea and vomiting were reported in 55 patients, and the risk was 2.92 times greater in the menstrual group (71.4%) than in the nonmenstrual group (46.2%; (P = .013). Droperidol (30 micrograms/kg) reduced the incidence of vomiting from 47.1% (placebo) to 13.3% in the nonmenstrual group (P = .045) but had no effect in the menstrual group. Five prognostic variables (menstrual stratum, droperidol, age 30 yr or younger, weight 65 kg or less, and history of nausea and vomiting) for postoperative nausea and vomiting were tested by stepwise logistic regression. Menstrual stratum was the only variable identified as a significant (P = .017) predictor, having a percent probability equal to 2.21. CONCLUSIONS: The risk of postoperative nausea and vomiting is increased in women undergoing laparoscopic tubal sterilization during the first 8 days of their menstrual cycle, and droperidol up to 30 micrograms/kg is not as effective in these patients. PMID- 8439023 TI - Hemodynamic and analgesic actions of epidurally administered clonidine. AB - BACKGROUND: alpha 2-Adrenergic agonists such as clonidine produce behavioral analgesia and cardiovascular depression in animals, but clonidine's site of action in clinical analgesia and cerebrospinal fluid (CSF) pharmacokinetics have not been defined. METHODS: Clonidine was administered in the lumbar epidural space to nine volunteers while monitoring blood pressure, heart rate, finger and toe blood flow, and response to cold pain testing, and while sampling CSF and arterial plasma for clonidine analysis. Effects were correlated to plasma and CSF clonidine concentrations. Ten other volunteers received stepped intravenous infusions of the opioid alfentanil with similar testing. RESULTS: Clonidine decreased pain report in the foot but not the hand, and this effect correlated stronger with CSF than with plasma clonidine, suggesting a spinal site for analgesia. Extrapolation of CSF clonidine pharmacokinetics suggests the minimum effective CSF clonidine concentration for postoperative pain relief is 76 +/- 15 ng/ml. Clonidine increased finger and toe blood flow, decreased blood pressure and heart rate, produced sedation, and mildly increased arterial PCO2, in most cases correlating better with plasma than CSF clonidine concentrations, suggesting actions at central sites. In 10 other volunteers, intravenous infusion of the opioid alfentanil produced analgesia of similar intensity to clonidine but was accompanied by significant respiratory depression. CONCLUSIONS: These data support previous studies in animals and provide the scientific rationale for this novel analgesic therapy. In comparison to the potent opioid alfentanil, epidural clonidine produces a similar degree of analgesia but less respiratory depression. PMID- 8439024 TI - The effect of alfentanil on cerebral blood flow velocity and intracranial pressure during isoflurane-nitrous oxide anesthesia in humans. AB - BACKGROUND: Intravenous opioids often are used as a component of anesthesia during neurosurgical procedures. However, the cerebrovascular effects of alfentanil administered to patients are controversial. In this study, the effect of alfentanil in patients with and without intracranial pathology was studied. METHODS: Sixteen neurosurgical patients and 16 patients scheduled for orthopedic procedures were studied. Anesthesia was maintained with isoflurane (0.4-0.6 vol% inspired) and nitrous oxide (50%) in oxygen. Within each group, the patients were assigned randomly to receive either 25 or 50 micrograms/kg intravenous alfentanil. During normocapnia and without surgical stimulation, the right middle cerebral artery flow velocity, and mean arterial pressure were measured every minute for 10 min after the administration of alfentanil. In the neurosurgical patients, intracranial pressure, cerebral perfusion pressure, and cerebral arteriovenous oxygen content difference were determined also. Neurosurgical patients received intravenous phenylephrine to maintain mean arterial pressure as needed. RESULTS: There was no significant change in middle cerebral artery flow velocity and arteriovenous oxygen content difference in the neurosurgical patients. In the high-dose group, intracranial pressure increased by 2 mmHg at 4 min but was otherwise unchanged. Despite phenylephrine administration, there was an immediate but transient decrease in mean arterial pressure in the high-dose group and a corresponding decrease in cerebral perfusion pressure. In the orthopedic patients, mean arterial pressure decreased significantly. Middle cerebral artery flow velocity decreased in the high-dose group but remained unchanged in the low-dose group. CONCLUSIONS: Based on the flow velocity and metabolic data, alfentanil is neither a cerebral vasodilator nor a vasoconstrictor in these doses. Furthermore, there was no clinically significant increase in intracranial pressure when alfentanil was administered in either dose. PMID- 8439025 TI - Direct in vivo visualization of bronchodilation induced by inhalational anesthesia using high-resolution computed tomography. AB - BACKGROUND: Volatile anesthetics are effective at preventing and reversing bronchospasm, but their effects on baseline airway tone are controversial. While tantalum bronchography has been used in the past to measure one-dimensional airway diameter changes, this method has inherent problems associated with the irritant effects of tantalum. Until recently, no other direct noninvasive in vivo method to assess airway caliber was available. The present investigation assesses the effects of the inhalation anesthetic halothane on individual unstimulated airways in vivo. METHODS: Ten studies were performed in seven dogs. All dogs were initially anesthetized with 15 mg/kg thiopental followed by a 10-mg.kg-1 x h-1 maintenance dose. Following tracheal intubation the lungs were mechanically ventilated (15 ml/kg, 15 beats/min). The dogs subsequently received increasing doses of halothane (range 0.5-1.5%). On a separate day, the dogs were pretreated with atropine (0.2 mg/kg) and the study was repeated. Fifty sequential high resolution computed tomography scans were obtained using a 1-s scan time, 137 kVp, 220 mA, 2-mm slice thickness, and 1-mm table feed. Airway areas ranging in size from 3 to 22 mm in diameter were measured and analyzed by one way analysis of variance and Bonferroni pair-wise comparisons of means. RESULTS: Halothane in concentrations of 0.5%, 1.0%, and 1.5% showed significant dose-dependent dilation of the airways (percent increase from control) that averaged 90 +/- 19% (mean +/- SEM), 128 +/- 20%, and 182 +/- 27%, respectively (P = .017). Atropine pretreatment alone significantly dilated the airways to 151 +/- 25% (P = .002) of their baseline value. Halothane caused no further airway dilation in atropine pretreated dogs. CONCLUSIONS: Halothane dilates baseline airways by blocking baseline vagal tone. Since baseline airway tone, airway wall thickness, and initial airway diameter are major determinants of airway reactivity, the observed dilation by halothane may be one of the mechanisms by which inhalational anesthetics decrease airway reactivity. PMID- 8439026 TI - Neostigmine counteracts spinal clonidine-induced hypotension in sheep. AB - BACKGROUND: Intraspinal clonidine injection produces analgesia free of respiratory depression, but also decreases blood pressure and causes sedation. Spinal neostigmine injection alone increases blood pressure in animals and enhances clonidine-induced analgesia. METHODS: To test whether neostigmine would alter clonidine-induced hypotension, nine chronically prepared sheep received intrathecal injections of saline or neostigmine (150, 300, 1,000 micrograms) followed in 15 min by 200 micrograms clonidine. RESULTS: Clonidine plus saline decreased mean arterial pressure by 12 +/- 3% associated with small, statistically nonsignificant decreases in heart rate, cardiac output, and systemic vascular resistance. Prior injection of neostigmine diminished hypotension 60 min after clonidine injection in a dose-dependent manner. To further define the time course and pharmacology of this interaction, seven other sheep received intrathecal saline, neostigmine (1,000 micrograms), or neostigmine plus methylatropine (1,000 micrograms) 75 min prior to 200 micrograms clonidine. With this longer interval between injections, neostigmine abolished clonidine induced hypotension, and this protective effect was inhibited by methylatropine. To test whether rostral spread of neostigmine in cerebrospinal fluid would alter its hemodynamic effects, we injected intrathecal neostigmine into the upper cervical site. Intrathecal neostigmine increased mean arterial pressure and heart rate at this site to a degree similar to that in the thoracic area, with no effect on behavioral or arterial blood gas tensions. CONCLUSIONS: These data are consistent with neostigmine's counteraction of clonidine-induced hypotension by a spinal muscarinic mechanism and support investigation of spinal alpha 2 adrenergic-cholinergic combinations for pain therapy. PMID- 8439027 TI - The role of focal nerve ischemia and Wallerian degeneration in peripheral nerve injury producing hyperesthesia. AB - BACKGROUND: A new model of pain associated with an experimental peripheral mononeuropathy has stimulated interest in mechanisms of pain and their structural correlates in peripheral nerve, the site of the experimental lesion. METHODS: The pathology of the neuropathy was studied and the results correlated with alterations in nerve blood flow and with the behavioral response to heat applied to the foot. The focal neuropathy was created by loosely tying several ligatures around rat sciatic nerve, which produces hyperesthesia in the ligated limb in 3-5 days. The neuropathology was striking with epineurial and endoneurial vascular stasis, edema, and extensive nerve fiber injury in the ligated segment noted at 1 week after ligation. RESULTS: Nerve blood flow was reduced significantly in the ligated segment during the development of the hyperesthesia response, suggesting that changes in nerve blood flow caused by the ligature compression of the epineurial vessels contributes to the nerve fiber injury and pathophysiology of the model. To further test this hypothesis, the epineurial vasculature was removed from 1-cm lengths of rat sciatic nerve, which reduces nerve blood flow by 58%, and by ligation of the ipsilateral femoral artery, which focally reduces nerve blood flow by 70%, and the behavioral response to heating of the paw was evaluated at 1 week. Crush injury was used as a positive control creating Wallerian degeneration without a substantial reduction in nerve blood flow. CONCLUSIONS: The results suggest that ischemia is an important initial pathogenic mechanism in the hyperesthesia associated with the loose ligature pain model, in so far as it produces Wallerian degeneration and axonal injury. Modest degrees of ischemia producing only demyelination did not produce significant hyperesthesia. PMID- 8439028 TI - Enflurane, halothane, and isoflurane attenuate contractile responses to exogenous and endogenous norepinephrine in isolated small mesenteric veins of the rabbit. AB - BACKGROUND: Volatile anesthetics exert both direct and indirect (neurally mediated) effects to produce splanchnic venodilation. These effects may result in clinically relevant hemodynamic changes. The present study examined the direct effects of isoflurane, halothane, and enflurane on rabbit mesenteric venous smooth muscle. METHODS: Changes in isometric tension, in response to exogenous and endogenous norepinephrine, were measured in isolated mesenteric vein rings before and during the administration of volatile anesthetics. RESULTS: Exogenous and electrically evoked endogenous norepinephrine produced an increase in tension with super-imposed rhythmic oscillations in tension. The exogenous norepinephrine induced increase in tension was augmented in the presence of NG-nitro-L-arginine methyl ester (L-NAME, 5 x 10(-5) M). The oscillatory activity was not altered by L-NAME. The increase in isometric tension in response to electrical stimulation was inhibited by phentolamine (5 x 10(-6) M) and tetrodotoxin (3 x 10(-6) M). Equianesthetic (1 MAC) concentrations of isoflurane, halothane, and enflurane significantly attenuated contractile responses to exogenous and endogenous norepinephrine, with isoflurane demonstrating a more depressant effect than halothane or enflurane. Volatile anesthetics also suppressed the amplitude and frequency of oscillations in the control as well as L-NAME-treated veins. The inhibitory effects of volatile anesthetics on the oscillations were comparable to the effects of ryanodine, a specific blocker of calcium channels in sarcoplasmic reticulum. CONCLUSIONS: These results suggest that: 1) vascular endothelium, via endothelium-derived relaxing factor, modulates exogenous norepinephrine responses of the venous smooth muscle; 2) the oscillatory behavior of mesenteric veins may be attributed to calcium fluxes in the venous smooth muscle cells; and 3) the norepinephrine-dependent increases in contractile and oscillatory activity are attenuated more by isoflurane than halothane or enflurane. This indicates that volatile anesthetic-mediated splanchnic venodilation is, at least in part, due to a direct action on vascular smooth muscle as well as withdrawal of sympathetic tone. PMID- 8439029 TI - Focal cerebral ischemia in rats. Effect of hypervolemic hemodilution with diaspirin cross-linked hemoglobin versus albumin on brain injury and edema. AB - BACKGROUND: Hemodilution has had limited success as a treatment of cerebral ischemia. When using a non-oxygen-binding fluid, the therapeutic efficacy of hemodilution-induced increases in blood flow are offset by concomitant decreases in oxygen content. METHODS: The effect of hemodilution, with diaspirin cross linked hemoglobin (DCLHb), on brain injury and edema was assessed during middle cerebral artery occlusion (180 min) and reperfusion (120 min) in rats (blood volume increased by approximately 30% and n = 10 for each group): (1) 44/B: 8.0 ml of donor blood was given; (2) 30/albumin: hematocrit was decreased to 30% with 10% albumin; (3) 30/DCLHb: hematocrit was decreased to 30% with 10% DCLHb; or (4) 9/DCLHb: hematocrit was decreased to 9% with DCLHb. Infarct size was analyzed with 2,3,5-triphenyltetrazolium chloride, and edema by microgravimetry. RESULTS: Brain injury (percent of the hemispheric area ipsilateral to ischemia, mean +/- SD) was greater in the 44/B group (44 +/- 4) versus the 30/albumin group (37 +/- 3). In addition, brain injury was greater in the 44/B and 30/albumin groups versus the 30/DCLHb group (27 +/- 4); which was in turn greater than the 9/DLCHb group (18 +/- 3). Specific gravity was greater (less brain water) in all hemodiluted groups versus the 44/B group. CONCLUSIONS: These results support a hypothesis that hemodilution decreases focal cerebral ischemic injury, and when an oxygen-binding fluid is used, there is a dose-dependent effect of hemodilution on ischemia. In addition, these results suggest that hemodilution, as achieved with DCLHb, was more effective in reducing ischemic brain damage than was the same degree of hemodilution as achieved with albumin. PMID- 8439030 TI - Myocardial hypercarbic acidosis reduces cardiac resuscitability. AB - BACKGROUND: The severity of spontaneous myocardial hypercarbic acidosis during cardiac arrest previously has been predictive of the likelihood of restoring spontaneous circulation. The present study investigated whether hypercarbia itself impairs cardiac resuscitation. Since coronary perfusion pressure is the overriding determinant of cardiac resuscitability, we used a porcine model of cardiac arrest in which coronary perfusion pressure was controlled. METHODS: In 31 domestic pigs anesthetized with pentobarbital, the lungs were mechanically ventilate. Myocardial carbon dioxide tension and hydrogen ion concentration were measured by sensors advanced into the myocardium. After 15 min of untreated ventricular fibrillation, venoarterial extracorporeal circulation was initiated. Animals were randomized to receive a carbon dioxide gas fraction in the extracorporeal perfusate of 0.00, 0.10, 0.30, or 0.50 with oxygen concentration maintained constant at 0.50. Extracorporeal flow was adjusted to maintain a coronary perfusion pressure in the range of 60-80 mmHg, a level of predictive resuscitability. RESULTS: The proportion of animals successfully resuscitated and the proportion of animals maintaining spontaneous circulation for 60 min or longer decreased with increasing perfusate PCO2 and concurrent increases in myocardial CO2 tension in the absence of altered oxygen utilization (P < .01). CONCLUSIONS: Hypercarbia, in this experimental setting, was therefore a quantitative determinant of both myocardial resuscitability and the restoration of spontaneous circulation. PMID- 8439031 TI - Dorsal scapular nerve block: description of technique and report of a case. PMID- 8439032 TI - False desaturation due to intradermal patent blue dye. PMID- 8439033 TI - Ipsilateral shoulder pain following thoracic surgery. PMID- 8439034 TI - High-titer protamine-specific IgG antibody associated with anaphylaxis: report of a case and quantitative analysis of antibody in vasectomized men. PMID- 8439035 TI - Acute right ventricular failure after pulmonary hypertensive responses to airway instrumentation: effect of fentanyl dose. PMID- 8439036 TI - Intraoperative pacemaker-mediated tachycardia: a complication of dual-chamber cardiac pacemakers. PMID- 8439037 TI - Practice guidelines for pulmonary artery catheterization. A report by the American Society of Anesthesiologists Task Force on Pulmonary Artery Catheterization. PMID- 8439038 TI - An easy, safe, and clean procedure to open propofol ampules. PMID- 8439039 TI - Atmospheric pollution with topical anesthetics. PMID- 8439040 TI - Risk of ischemia in patients receiving desflurane versus sufentanil: sample size and clinical significance. PMID- 8439041 TI - Perioperative dislocation in a patient with a prosthetic hip. PMID- 8439042 TI - Prevention of awareness during total intravenous anesthesia. PMID- 8439043 TI - Hazards of supplying supplementary oxygen through main gas flowmeters. PMID- 8439044 TI - Hypotension and spinal anesthesia. PMID- 8439045 TI - Nitrous oxide--it's enough to make you vomit. PMID- 8439046 TI - Combined spinal-epidural anesthesia using needle-through-needle technique. PMID- 8439047 TI - Overcoming the language barrier in obstetrics anesthesia practice. PMID- 8439048 TI - Anesthesia for children with Freeman-Sheldon syndrome. PMID- 8439049 TI - Playing a key role in the "Decade of the Brain". PMID- 8439050 TI - Nurses grapple with restraint issue. PMID- 8439051 TI - Symposium says health care reform must include mental health care. PMID- 8439052 TI - Bringing mental health care to Russia. PMID- 8439053 TI - Psychiatric liaison nursing: a ready help in organizational change. PMID- 8439054 TI - Refuting some myths about psychiatric nursing. PMID- 8439055 TI - ANA advocates APNs for primary care. PMID- 8439056 TI - Restructuring health care includes discussing options. PMID- 8439057 TI - Registered nurses show true spirit of Christmas. PMID- 8439058 TI - Clinic provides a helping hand for mentally ill, homeless women. PMID- 8439059 TI - Psych/mental health nurses care patients as a team. PMID- 8439060 TI - ANA contemplates development of national policy statement on UAP. PMID- 8439062 TI - 18: a magic number in proper immunization procedures. PMID- 8439061 TI - Nursing and professional boundaries: legal barriers to practice. PMID- 8439063 TI - American RNs reach out to Romanian colleagues. PMID- 8439064 TI - Study shows nurse practitioner care may rival physician primary care. PMID- 8439065 TI - New nurses need not fear "reality" of acute care settings. PMID- 8439066 TI - Taking bold, uncharted steps--ANA is getting positioned. PMID- 8439067 TI - The 'possible' dreams of mental health reform. PMID- 8439068 TI - American Nurses Association Position Statement on registered nurse utilization of unlicensed assistive personnel. PMID- 8439069 TI - [Early detection of deafness in infancy. Theory vs. practice]. PMID- 8439070 TI - [Urinary concentration capacity in neonatal hydronephrosis]. AB - In order to determine the renal concentration capacity in neonatal hydronephrosis, 10 micrograms of DDAVP were administered intranasally to 18 infants with hydronephrosis. Fluid intake was restricted to 50% of normal for 3 hours before and 6 hours after the administration of DDAVP. Maximal urine osmolality (mean +/- SD) was 348 +/- 180 mOsm/kg in 7 newborns younger than 21 days and 420 +/- mOsm/kg in 11 neonates between 22-50 days of age. Both osmolarities were inferior to the standard response to DDAVP reported in normal neonates. After 24 hours of clinical observation, we did not notice any secondary effects caused by this test. PMID- 8439071 TI - [Blastocystis hominis and abdominal pain in childhood]. AB - We report the clinical features observed in 10 children, ranging from 5 1/12 to 13 7/12 years of age, with intestinal infections caused by Blastocystis hominis. A parasitological study of the stools was made by using the ethyl-acetate formol concentration technique and a count of the number of B. hominis per field was performed. In 8 of the cases, no other enteropathogens (viruses, bacteria or other parasites) were found, whereas in 2 cases Giardia lamblia was also isolated. Nine out of ten of the patients presented with abdominal pain. In three of the cases it appeared as a pseudo-appendicular ailment which led to an appendectomy. Those children who were treated with metronidazole and those who were not treated with antibiotic recovered satisfactorily. PMID- 8439072 TI - [Acute intestinal invagination: hydrostatic reduction vs. pneumatic reduction]. AB - We report the results of 100 cases of acute intussusception treated by inflation of the colon with air under controlled pressure. We compare this method with the traditional one and we analyse the advantages of each method. Successful reduction was achieved in 76% of the cases of intussusception treated with a barium enema and in 88% of the cases treated with an air enema. Pneumocolon in the treatment of acute intestinal intussusception is an alternative method that is very effective and with additional advantages such as: less radiation, less cost and less morbidity in case of perforation. PMID- 8439073 TI - [Early discharge of low-birth-weight neonates. 5-year experience]. AB - The object of this study was to determine whether the hospital stay could be reduced in low birth weight infants without any risk. A prospective, controlled and randomized study has been made with 80 newborn infants with birth weights < or = 2.000 gm. The infants of the experimental group (n = 40) were discharged with weights < or = 2.000 gm and the control group (n = 40) were discharged with weights > or = 2.000 gm. Both groups showed similar social, economic, perinatal and postnatal conditions. We have found significant advantages in the experimental group such as: reducing the period of hospitalization (p = 0.005), greater weight increase (p < 0.001), a longer breast feeding period (p = 0.02) and a 29% reduction in expenditures. The follow-up shows that there are no significant differences between the groups regarding morbidity, mortality, growth or psychomotor development. We conclude that there are no disadvantages, but considerable advantages, in early discharge of low birth weight infants. PMID- 8439074 TI - [Splenectomy in childhood. Review of a case load]. AB - We review the cases of splenectomy performed in children between 1974 and 1988. During this period, we performed 24 splenectomy procedures, none of which were done as a result of injury. Most patients were between 5 to 10 years of age and had the splenectomy as a result of hemolytic disease. Antibiotic prophylaxis and anti-pneumococcic vaccination preceded splenectomy, resulting in a low morbidity and mortality. This report emphasizes the indications for splenectomy, a decrease in its frequency, variations in its etiology and the low incidence of surgical complications. PMID- 8439075 TI - [Randomized double-blind study of treatment of croup with adrenaline and/or dexamethasone in children]. AB - We present the results of a study designed to verify the efficacy of nebulized L Adrenaline and/or dexamethasone given intramuscularly (IM) in the treatment of croup during childhood. Sixty-six children, hospitalized for croup during the period between october 1989 and september 1990, entered the study. They received the ordinary treatment with oxygen-therapy and fluid-therapy and were randomly assigned, in a double-blind fashion, into one of four treatment groups: Group 1: Nebulized L-Adrenaline and placebo (IM). Group 2: Nebulized saline and placebo (IM). Group 3: Nebulized saline and dexamethasone (IM). Group 4: Nebulized L Adrenaline and dexamethasone (IM). The clinical evaluation was based on a scoring system assessing the inspiratory stridor, croupy cough, retractions and cyanosis. An analysis of variance was performed on the evolution of the score for two factors (Adrenaline and dexamethasone) to verify that there was no interaction between them. Subsequently, a one-factor analysis of variance was performed on the four treatment groups. We conclude that nebulized Adrenalin is more beneficial than saline in the clinical evolution of croup (p < 0.05). However, we did not find a statistically significant improvement in the group treated with dexamethasone when compared with the group treated with the placebo IM injection. PMID- 8439076 TI - [Transcutaneous bilirubin measurement in neonates]. AB - A study was performed to determine, in our population, the relationship between transcutaneous, visual and serum bilirubin values. This was done in attempts to reduce the number of serum bilirubin determinations to be performed in the future. We did a correlation coefficient between serum bilirubin and five measurements of transcutaneous bilirubin levels in a group of 60 term newborns and 60 preterm newborns, obtaining a value of 0.84 in both groups. The results were also considered from an analytical point of view where the ability of the test to predict an alteration in serum bilirubin levels, for example > or = 12 mg/dl in preterm and > or = 13 mg/dl in term newborns, was assessed. For values of 18 in preterm and 17 in term infants, the transcutaneous method was found to be both sensitive and specific. If Kramer's test is also evaluated the results improve. PMID- 8439077 TI - [Epidemiologic study of accidental poisoning cases treated at a pediatric hospital]. AB - A prospective study, by epidemiological survey, was carried out in the 447 children with acute poisoning attended in our hospital between February 1, 1990 and January 31, 1991. All data was processed to analyze the possible associations that would help to better understand the factors that take part in poisoning. We observed a predominance in male infants, with a greater incidence between two and three years of age, and the accidents occurred almost exclusively at home, mainly in the kitchen or bedroom. The child is often not adequately watched and the toxic elements are usually within easy access. There was neither a seasonal nor daily predominance. We noticed an hourly predominance with most accidents occurring between 12 a.m. and 4 p.m. Drugs are the most common agents, followed by household cleaning products. Morbidity was scarce and there was no mortality. PMID- 8439078 TI - [Neurologic evolution of premature infants following assisted ventilation, with and without bronchopulmonary dysplasia]. AB - The aim of this work was to evaluate the influence of bronchopulmonary dysplasia on the neurological outcome of the preterm infant requiring assisted ventilation. Thirty-nine preterm infants requiring ventilation support during 72 hours or more were classified into two groups according to the presence or absence of bronchopulmonary dysplasia (BPD). In the BPD group (n = 11), only the incidence of mild cognitive deficits was significantly higher (36.4 % vs 0 %). Our results suggest that the neurological outcome of the infants with BPD is more closely associated with other neonatal events (intraventricular hemorrhage, periventricular leukomalacia, neonatal seizures, longer ventilation support, maximum serum bilirubin levels, low Apgar score at 10 minutes and poor intake of amino acids) than with the presence of BPD. The data of this study suggest that indomethacin reduces the risk of neurological deficits. PMID- 8439079 TI - [Alcohol and tobacco consumption of middle school students in the municipality of Madrid]. AB - We studied alcohol and tobacco abuse un 842 students from 24 different schools in Madrid. The information was obtained from validated questionnaires adapted to our country. The most important outcomes were: 43% of the students drank alcohol at least once a week (especially on weekends). Most of the consumption was moderate on working days, but increased significantly on feastdays P < 0.001). Twenty seven percent of the students smoked daily and 17% smoked occasionally. Of these students, 69% smoked less than 10 cigarettes per day (c/d), 28% 10-20 c/d and 3% more than 20 c/d. They usually started smoking and drinking at 14 years of age. Men drank more frequently and heavier than women, but there were no sex differences in tobacco usage. We did not find any differences between social status or type of school. PMID- 8439080 TI - [First centenary of birth of Prof. Fanconi (1892-1979)]. PMID- 8439081 TI - [Jarcho-Levin syndrome: report of three cases. Associated extra-skeletal malformations]. PMID- 8439082 TI - [Congenital oculomotor apraxia associated with duplication of band P13 of chromosome 5. Review of the literature]. PMID- 8439083 TI - [Acquired postnatal intestinal atresia]. PMID- 8439084 TI - [Unilateral hyperlucent lung in a child]. PMID- 8439085 TI - [Autoimmune thyroiditis diagnosed while studying pericardial effusion in a Down syndrome patient]. PMID- 8439086 TI - [Study of the gene of Duchenne muscular dystrophy using PCR analysis]. AB - We have performed the polymerase chain reaction (PCR) to study 26 patients affected with Duchenne muscular dystrophy as a direct diagnostic method of screening for gene deletions. We have amplified simultaneously 9 sequences which belong to 9 exons located along the two "hot spots" of the gene. We have detected deletions in many of the exons in 11 of the 26 patients (42.3% of the cases). PMID- 8439087 TI - [Hepatitis B2 in childhood]. PMID- 8439088 TI - [Genital prolapse in a newborn infant]. PMID- 8439089 TI - [Acute hemorrhagic edema in an infant]. PMID- 8439090 TI - [Hirschsprung disease and primary central hyperventilation syndrome: a new form of neurocristopathy]. PMID- 8439091 TI - [Breast feeding and the infant food industry: two contrasting terms?]. PMID- 8439092 TI - [Fluoride content in formulated milk]. PMID- 8439093 TI - [Iron deficiency anemia: a current problem]. PMID- 8439094 TI - [Relationship between primary lactose malabsorption and consumption of dairy products]. AB - This study was designed to determine the influence of lactose malabsorption on the consumption of dairy products. We studied 157 children and 43 adults. The Breath-hydrogen test was used to define their level of lactose digestion. The prevalence of lactose maldigesters was 12%. We found a large relationship between the consumption of milk and milk products and age. Malabsorbers consumed more fermented dairy products (ripened cheese and yogurt) than did absorbers (p < 0.05). Subjects with normal lactose absorption consumed more milk, butter, cream cheese and global lactose than the maldigesters (p < 0.05). Lactose intolerance, familiar consumption and geographic origins had little influence on an individual's consumption habits. PMID- 8439095 TI - [Folic acid and vitamin B12 in children under long-term anticonvulsant therapy]. AB - Folic acid (FA) and vitamin B12 have been measured prospectively in 110 children that were under treatment with anticonvulsants. The control group consisted of 59 healthy children. A statistically significant difference in levels of serum FA and mean corpuscular volume (MCV) was observed between groups. Children under anticonvulsant treatment had lower serum FA levels and higher MCV. No significant difference was observed between the two groups in levels of serum vitamin B12. All children with serum FA levels lower than 3 ng/ml were given folate and no adverse side effects were observed due to treatment. Anticonvulsant drugs decrease serum FA levels; therefore, FA should be determined periodically in children under long-term anticonvulsant treatment. PMID- 8439096 TI - [Poisoning by viper bites in children]. AB - Our experience with 36 cases of adder bites, collected during 13 years (1976 1989), is presented. The severity of the clinical picture was minimal to moderate in most of the cases, with mainly local symptomatology noted. Only 4 of the cases had symptoms such as vomiting and abdominal pain. Good results wee obtain in all cases with the prescribed medical treatment, except in one case which had partial necrosis of the skin on one finger on the side of viper bite. Antibiotics were used in all cases except three and anti-tetanus therapy was used in those cases where needed. Corticosteroids and antihistamines were used on selected occasions. We recommend the use of antiofidic serum, although the possibilities of anaphylactic reaction must be noted. We do not recommended local incisions and suction for this type of bites. PMID- 8439097 TI - [Comparative study of tonal liminal audiometry and evoked otoacoustic emissions in school screening programs]. AB - Early diagnosis of deafness is an important objective during the pediatric age. This study compares two different audiological techniques, otoacoustic emissions (OEA) and tonal audiometry (AUD), to be used as screening methods in school revisions programmed for 6 years olds. The correlation between techniques is very good (97% of the positives and 92% of the negatives). The OEA method is objective and faster if the environmental noise is low; if not, AUD seems to be more reliable. At this age (6 years), the otoacoustic emissions have characteristics of the adult age. PMID- 8439098 TI - [Single or double dose of vaccine needed for the eradication of measles in Spain?]. AB - A descriptive and retrospective epidemiological study of measles vaccinations was realized. This study involved 112 children hospitalized in Valencia (Spain) for measles during the period from January 1983 to December 1988. We compared children that had received vaccination and those children that had not. Statistically significant differences were observed in regards to the age of the child (p < 0.025) and the year in which the cases were diagnosed (p < 0.05). The evolution of measles in Spain and in the United States shows the need for revaccinations, as well as the need to augment the coverage of vaccinations in order to eradicate this disease. PMID- 8439099 TI - [Femoral hernia in children]. AB - Femoral hernia is rare in adults and even less common in children, to the point that expert surgeons have limited experience with it. Eleven patients with femoral hernia have been operated upon in our service during the past 15 years. Preoperative diagnosis was made in 6 cases (54.5%), and we underline that the ideal therapy began with this early diagnosis. We review the etiologies, clinical findings and treatment of femoral hernia in children. PMID- 8439100 TI - [Unilateral agenesis of the pulmonary artery. Experience with 4 cases]. AB - We present our experience with four cases of unilateral pulmonary agenesis, 3 of the right artery and the other one of the left. Two of the patients had pulmonary hypertension and one of them died at two years of age. All cases were diagnosed by using pulmonary angiography. Aortography demonstrated the absence of circulatory supply to the lung and a contralateral aortic arch to the absent pulmonary artery. We have performed a review of the literature with an emphasis on the diagnostic aspects of this condition, and discuss the considerations for possible surgery in symptomatic patients. PMID- 8439101 TI - [Insulin resistance and clinical evolution in infantile myotonic dystrophy]. AB - We present the results of a 13 year follow-up of seventeen children with myotonic dystrophy, with the aim of better understanding the progression of this disease. We want to emphasize two basic aspects; first, the detection of myotonia with the use of EMG during the first five years of life when the clinical profile is suggestive of the disease, previous reports have stated that this sign appears relatively late in the disease process, and secondly, we want to point out that more than 50% of these patients showed insulin-resistance starting from the sixth year of life. This aspect of the disease has been well described in adult patients, but is practically absent in the pediatric literature. Hyperinsulinemic subjects demonstrated an intellectual quotient significantly lower than those subjects with normal insulin levels (p < 0.01). Basal insulin levels also had a predictive value in relation to the rest of the points n the insulin curve. The changes in insulin resistance are discussed in relation to cellular membrane changes present in myotonic dystrophy. PMID- 8439102 TI - [Study from Navarra. Variations in the average arterial blood pressure level according to age, gender and body height]. AB - As part of an epidemiological study on cardiovascular risk factors among children and adolescents in Navarra, arterial blood pressure (BP) readings were taken in 5,829 children, including both sexes and aged between 4 and 17 years. The subjects were randomly selected from the public and private school population in our community. BP-age and BP-height percentiles were obtained for each sex and the physiological variations in BP according to these parameters was also analyzed. Systolic BP increased with age in both sexes throughout childhood. During adolescence, there is almost no variation in BP among girls, but in boys older than 13 years, there is a sudden increase. For this reason, boys have higher values than girls. Diastolic BP shows a linear increase in both sexes. BP increases with height in both sexes. In spite of the sudden rise in systolic BP among the boys taller than 145 cm, the increase in systolic BP in relationship to height is smaller and more homogeneous than the increase seen with age. As the BP variations with height are smaller and more homogeneous than those related to age, it is preferable to evaluate this parameter by BP-height rather than by BP age. PMID- 8439103 TI - [Study from Navarra. Hyperlipidemia II. Variations according to age and sex in the average cholesterol level, LDL-cholesterol and triglycerides in an infant child population]. AB - As part of an epidemiological study on cardiovascular risk factors among children and adolescents in Navarra, lipids and lipoproteins were analysed in 5,829 children. The study group was selected at random from the school population in our community and included students of both sexes between 4 and 17 years of age. In this article we describe the variations from 4 to 10 years of age in both sexes and decrease from that age on. Among males older than 14, they continue decreasing, while they become stable in females. For this reason, values during childhood are higher than during adolescence in both sexes, and within this period, males show lower levels than girls. Variations in LDL serum levels according to age and sex are similar to those recorded with cholesterol. The triglyceride serum levels increase in line with age among boys. With girls, something similar happens until they are 13. Starting from this age, there is an inversion showing lower levels than the male adolescents. In both sexes, levels during adolescence are higher than during childhood. PMID- 8439104 TI - [Nutritional management of acute infectious diarrhea of mild and moderate intensity]. AB - In childhood, acute infectious diarrhea remains one of the most important causes of mortality (due to dehydration) and morbidity (due to malnutrition). Whilst, the introduction of solutions for oral rehydration have meant a therapeutic advance of extraordinary importance to meet the objective of avoiding or correcting the dehydration, the nutritional management of the child with acute diarrhea remains a subject of great controversy. Evidence that suggests that the mild or moderate forms of the illness do not cause functional or anatomic alterations in the gastrointestinal apparatus of the severity or duration described in the more severe forms of diarrhea, makes necessary a new therapeutic focus which, together with the rehydration, takes into account the nutritional aspect. In this report, we analyze the factors that justify the early reintroduction of easily digested nutrients in children with acute infectious diarrhea and we propose different models of refeeding according to age, type of previous feeding, severity of the diarrhea, the hydrational and nutritional status at the time of suffering the infection, and social/family environment of the patient. PMID- 8439105 TI - [Chronologic study of signs of myocardiopathy in progressive muscular dystrophy]. AB - In order to analyze the evolution of cardiomyopathy in progressive muscular dystrophies, thirty-three patients (17 with Duchenne type, 11 with Becker type and 5 with the autosomal recessive type dystrophy) were studied retrospectively. Cardiac and systemic follow-up every 3-6 months was made in 29 patients. The electrocardiogram was the first test that became altered, followed by the echocardiogram and thoracic radiograph and finally heart failure manifestations. There was a direct correlation between age and the appearance of abnormal cardiac tests. Electrocardiographic alterations, in patients who were less than 12.5 years of age, were significantly more frequent in the group with Duchenne dystrophy that in the no-Duchenne group. In regards to the appearance of the echocardiographic and radiographic abnormalities, there were no significant differences between the two groups. However, we have noticed a trend towards a more frequent and earlier presentation of these abnormalities in the Duchenne's muscular dystrophy than in the no-Duchenne group. PMID- 8439106 TI - [Cardiovascular calcifications in Gaucher disease]. PMID- 8439107 TI - [Mannosidosis. A clinical case]. PMID- 8439108 TI - [Childhood hemangiopericytoma. Apropos of a case]. PMID- 8439109 TI - [Campylobacter jejuni infection in the neonatal period. A potentially serious condition]. PMID- 8439110 TI - [Carbamazepine: serious intolerance in interstitial pneumonia, fever, exanthema and immunoglobulin deficiency]. PMID- 8439111 TI - [Congenital infection: current aspects]. PMID- 8439112 TI - Discontinuing rheumatic fever prophylaxis in selected adolescents and young adults. A prospective study. AB - OBJECTIVE: To assess the safety of discontinuing prophylaxis with antimicrobial agents in patients judged to be at relatively low risk for recurrence of acute rheumatic fever. DESIGN: Observational cohort study. SETTING: Public health clinics in the Southeast Health District of Santiago, Chile. PATIENTS: Fifty-nine patients (19 men, 40 women) ranging in age at study entry from 15 to 44 years (mean, 24.5 years). Forty-eight had completed their prescribed period of prophylaxis. Eleven refused or were allergic to intramuscular benzathine penicillin G and were non-compliant with oral sulfadiazine. INTERVENTION: In patients who did not have carditis during their previous attack(s), prophylaxis was discontinued after 5 years or at age 18, whichever was longer. In those with only mild mitral regurgitation or healed carditis, prophylaxis was stopped after 10 years or at age 25. Symptomatic intercurrent streptococcal throat infections were treated with antibiotics. MEASUREMENTS: Patients were seen every 3 months during the study (July 1982 to September 1988). For the first 4.25 years, throat cultures as well as sera samples for antistreptolysin O and anti-DNAse B assays were obtained at each visit. RESULTS: During laboratory surveillance, significant increases in antibody titers were detected in 56 instances (28.1 [95% CI, 21.7 to 36.5] per 100 patient-years), and 29 isolations of group A streptococci occurred (14.5 [CI, 10.1 to 20.8] per 100 patient-years). The patients were followed for a total of 3349 patient-months, during which time two acute rheumatic fever recurrences were observed (0.7 [CI, 0.2 to 2.6] per 100 patient-years). No recurrences occurred during an outbreak of acute rheumatic fever in 52 patients in the study area in 1986. CONCLUSIONS: These and other data indicate that acute rheumatic fever prophylaxis can safely be discontinued in young adults judged to be at low risk for recurrence and who are maintained under careful prospective surveillance. PMID- 8439113 TI - Efficacy of oral ondansetron in the prevention of emesis in outpatients receiving cyclophosphamide-based chemotherapy. The Ondansetron Study Group. AB - OBJECTIVE: To evaluate the efficacy and safety of oral ondansetron (Zofran) as an antiemetic in patients receiving cyclophosphamide-based chemotherapy. DESIGN: A multicenter, randomized, double-blind, stratified, placebo-controlled trial conducted between March 1989 and January 1990. SETTING: Twenty-seven oncology centers including university hospitals, community cancer centers, and private medical oncology practices. PATIENTS: A total of 349 chemotherapy-naive patients having their first cycle of cyclophosphamide (> or = 450 mg/m2)-based chemotherapy. Patients also received methotrexate (> or = 30 mg/m2) or doxorubicin (> or = 35 mg/m2). All patients were evaluated for safety and 318 (91%) were evaluated for efficacy. INTERVENTIONS: Patients were randomly assigned to one of four treatment groups: placebo, 1 mg, 4 mg, or 8 mg of ondansetron. Assigned study medication was taken three times per day for 3 consecutive days. MEASUREMENTS: Time and number of emetic episodes as well as degree of nausea were recorded by patients for each of the 3 study days. RESULTS: Compared with placebo, all three doses of ondansetron were superior (P < 0.001) in preventing vomiting and controlling nausea. A complete response (no emetic episodes) was observed in 19%, 57%, 65%, and 66% of patients in the placebo, 1-mg, 4-mg, and 8 mg ondansetron groups, respectively. For patients who received higher-dose cyclophosphamide and doxorubicin, a dose-related trend in antiemetic efficacy of ondansetron was observed. Mild headache and constipation were the most frequently reported adverse events. No extrapyramidal reactions were observed. CONCLUSION: Oral ondansetron is a safe and effective antiemetic that is more efficacious than placebo for patients receiving cyclophosphamide-based chemotherapy. PMID- 8439114 TI - Clinical reactivation of herpes simplex virus type 2 infection in seropositive pregnant women with no history of genital herpes. AB - OBJECTIVE: To determine the risk for genital herpes and asymptomatic herpes simplex virus (HSV) shedding in late pregnancy and delivery in a population of HSV type 2 (HSV-2)-seropositive but previously asymptomatic pregnant women. DESIGN: A prospective inception cohort study. PARTICIPANTS: A total of 1355 pregnant women with no history of genital herpes referred from three private obstetrics practices between November 1985 and June 1988. MAIN OUTCOME MEASURES: Confidential questionnaires evaluated sexual risk factors in relation to HSV-2 serologic status as determined by Western blot analysis. Herpes simplex virus shedding was determined by viral culture of the cervix and vulva and of any suspicious lesions. RESULTS: Antibody to HSV-2 was detected in 439 of 1355 pregnant women (32%) with no history of genital herpes. Asymptomatic HSV shedding was detected in 5 of 1160 cultures (0.43%) obtained in late pregnancy and during delivery. A first episode of clinical genital herpes was recognized by 43 of 264 HSV-2-seropositive women (16%) during their pregnancy. CONCLUSIONS: Serologic evidence of unknown HSV-2 infection was common in pregnant women without a history of genital herpes. Asymptomatic viral shedding in these women occurred at a rate similar to that seen in women with symptomatic genital HSV-2 infection. To improve recognition of genital herpes near term, obstetricians should counsel pregnant women about the high prevalence and mild and diverse symptoms of genital HSV-2 infection. PMID- 8439115 TI - Incidence of postpartum thyroid dysfunction in patients with type I diabetes mellitus. AB - OBJECTIVE: To assess the incidence of postpartum thyroid dysfunction in women with type I diabetes. DESIGN: Cohort study of consecutive patients with clinical and biochemical assessments of thyroid dysfunction and glycemic control done during the first postpartum week and 3 and 6 months after delivery. SETTING: University medical center providing obstetric care for more than 90% of the pregnant women in the region with type I diabetes. PATIENTS: Fifty-one patients with type I diabetes who resided in the Hamilton, Ontario, catchment area and who delivered babies between May 1989 and June 1991, were not taking thyroid medication or thyroactive or immunosuppressive medications. Forty patients completed follow-up. MAIN OUTCOME MEASURES: Postpartum thyroid dysfunction was defined on the basis of thyroid function test results. RESULTS: Postpartum thyroid dysfunction occurred in 10 of 40 patients (25%; 95% CI, 12.7% to 41.2%); postpartum thyroiditis developed in 9 patients and postpartum Graves disease developed in 1 patient during the first 6 months after delivery. The incidence could have varied between 19.6% and 41.2% , depending on whether none or all of the 11 nonparticipating eligible patients developed thyroid dysfunction. Glycemic control was not affected by thyroid dysfunction. CONCLUSIONS: Women with type I diabetes are at a high risk for symptomatic postpartum thyroid dysfunction and therefore may benefit from routine thyroid function screening at postpartum visits. PMID- 8439116 TI - Hepatic injury during propylthiouracil therapy in patients with hyperthyroidism. A cohort study. AB - OBJECTIVE: To evaluate the incidence, severity, and course of propylthiouracil induced hepatic injury in patients with hyperthyroidism. DESIGN: Cohort study. SETTING: Outpatient clinic of a university-based hospital. PATIENTS: Fifty-four patients with normal aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values and a definite diagnosis of hyperthyroidism. INTERVENTION: Treatment with propylthiouracil, 300 mg/d for 2 months followed by 100 to 150 mg/d for 3 months and a subsequent maintenance dose of 100 mg/d. MEASUREMENTS: Liver biochemical tests were studied before therapy and 2 months and 5 months after starting propylthiouracil therapy. The patients were monitored with clinical evaluation and weekly liver biochemical tests after AST or ALT levels became abnormal. Serologic markers of hepatitis A, B, C, and delta virus infection were also studied when appropriate. RESULTS: Fifteen (28%; 95% CI, 16% to 42%) of the 54 patients showed ALT elevations 2 months after propylthiouracil therapy. The mean peak ALT level for these patients was 1.35 mu kat/L (range, 0.65 3.85 mu kat/L). None of these patients had symptoms or hyperbilirubinemia. Liver biopsy in three patients showed mild perivenular focal necrosis or ill defined granuloma composed of foamy histiocytes with ceroid pigment and mild fatty metamorphosis. Despite continued propylthiouracil therapy at a reduced dose, ALT levels returned to normal in 13 of 15 patients in the following 3 months. None of these ALT elevations resulted from hepatitis A, B, C, or delta virus infection. No statistical difference was seen in the pretreatment characteristics between patients with and those without ALT elevation, except that the former had a higher pretreatment T4 level (270 +/- 12.9 compared with 237 +/- 7.72 nmol/L, P = 0.027) and T3 level (7.22 +/- 0.72 compared with 5.85 +/ 0.39 nmol/L, P = 0.048). CONCLUSIONS: Propylthiouracil-induced subclinical liver injury is common and is usually transient and asymptomatic. Therapy with propylthiouracil may be continued with caution in the absence of symptoms and hyperbilirubinemia. PMID- 8439117 TI - Influence of sex hormones on plasma endothelin levels. AB - OBJECTIVE: To determine whether a sex-associated difference in endothelin levels exists and to assess whether this difference is mediated by sex hormones. DESIGN: Initial survey in healthy persons, followed by a nonrandomized intervention. SETTING: A university teaching hospital. PATIENTS: Twenty-three healthy men, 29 healthy women, 20 pregnant women, and 12 male-to-female and 13 female-to-male transsexual patients. MEASUREMENTS: Plasma levels of endothelin were first assessed in healthy men, healthy women, and pregnant women; subsequently, endothelin levels were determined in male-to-female and female-to-male transsexual patients both before and during cross-gender hormone treatment. This treatment involves administration of testosterone esters to women and of ethynylestradiol and cyproterone acetate to men. RESULTS: Endothelin levels were higher in men than in women (5.9 +/- 1.2 compared with 4.17 +/- 0.67 pg/mL; P < 0.01). Endothelin levels were lower in pregnant women than in age- and sex matched nonpregnant controls (2.19 +/- 0.73 compared with 4.17 +/- 0.67 pg/mL; P < 0.01). In 12 male-to-female transsexuals treated with estradiol and the progestational agent cyproterone acetate, endothelin levels decreased from 8.1 +/ 3.0 to 5.1 +/- 2.0 pg/mL (P < 0.01). In 13 female-to-male transsexuals treated with testosterone, endothelin levels increased from 6.2 +/- 1.1 to 7.8 +/- 1.2 pg/mL (P < 0.01). CONCLUSION: Sex hormones may modulate plasma endothelin levels, with male hormones raising levels and female hormones lowering them. This finding may be important in explaining sex-associated differences in susceptibility to atherosclerotic cardiovascular disease. PMID- 8439118 TI - Medical treatment of benign gastrocolic fistula. PMID- 8439119 TI - Heart rate variability. AB - PURPOSE: To present an overview of the applicability of heart rate variability measurements in medicine. DATA SOURCES: During a 4-year period all new papers concerning heart rate variability were collected. A selection of the most recent publications in the presented research area was used for this review. DATA SYNTHESIS: The amount of short- and long-term variability in heart rate reflects the vagal and sympathetic function of the autonomic nervous system, respectively. Therefore heart rate variability can be used as a monitoring tool in clinical conditions with altered autonomic nervous system function. In postinfarction and diabetic patients, low heart rate variability is associated with an increased risk for sudden cardiac death. A sympathovagal imbalance is also detectable with heart rate variability analysis in coronary artery disease and essential hypertension. Besides diabetic neuropathy, in many other neurologic disorders, such as brain damage, the Guillain-Barre syndrome, and uremic neuropathy, heart rate variability analysis can provide insight into which division of the autonomic nervous system is most affected. Heart rate variability can be influenced by various groups of drugs, but it can also shed light on the mode of action of drugs. The protective effect of cardiovascular drugs in postinfarction patients has been investigated. CONCLUSIONS: Heart rate variability analysis is easily applicable in adult medicine, but physiologic influences such as age must be considered. The most important application is the surveillance of postinfarction and diabetic patients to prevent sudden cardiac death. With heart rate variability analysis, individual therapy adjustments to achieve the most favorable sympathetic-parasympathetic balance might be possible in the future. PMID- 8439120 TI - Alternative perspectives on the biased foundations of medical technology assessment. AB - Medical technology assessment seeks to improve the care of individual patients (the conventional unit of clinical practice) through evaluation studies conducted in groups of patients (the conventional unit of clinical investigation). This distinction between individuals and groups has practical relevance to the design, analysis, and clinical applicability of technology assessment studies. We define several biased perspectives about technology assessment that derive from the distinction between individuals and groups: a misguided emphasis on efficacy versus effectiveness, on statistical significance versus clinical importance, and on objective versus subjective outcomes. In each case, we contrast these alternative perspectives and speculate on their implications for health care policy. PMID- 8439121 TI - Passing stones. PMID- 8439122 TI - Variation in group A streptococci and the prevalence of rheumatic fever: a half century vigil. PMID- 8439123 TI - Placebos and principles: a trial of ondansetron. PMID- 8439124 TI - Fecal occult blood tests for colorectal cancer. PMID- 8439125 TI - Fatal all-trans retinoic acid pneumonitis. PMID- 8439126 TI - Positional right-to-left shunting. PMID- 8439127 TI - Skin ulcers and tuberculosis outbreaks. PMID- 8439128 TI - When to discuss advance directives. PMID- 8439130 TI - Rx: an injection of energy. PMID- 8439129 TI - Human rights and medicine's obligations. PMID- 8439131 TI - Environmentalism. PMID- 8439132 TI - Laparoscopic instruments. Patient care, cost issues. PMID- 8439133 TI - Laparoscopic spermatic vein ligation. A new technique to treat varicoceles. PMID- 8439134 TI - Toupet partial fundoplication. Correcting, preventing gastroesophageal reflux. PMID- 8439135 TI - Differentiated nursing practice. A proposed model for perioperative practice. PMID- 8439136 TI - American Nurses Association publishes policies, documents on a variety of subjects related to AIDS/HIV. PMID- 8439137 TI - Nursing students--a precious resource. PMID- 8439138 TI - Preventing glove tears, sharp injuries. PMID- 8439139 TI - At-will employment. PMID- 8439140 TI - Proposed recommended practices. Laser safety in the practice setting. Association of Operating Room Nurses. PMID- 8439141 TI - Recommended practices. Traffic patterns in the surgical suite. Association of Operating Room Nurses. PMID- 8439142 TI - Identification and ecology of bacterial communities associated with necroses of three cactus species. AB - To compare the bacterial communities residing in necrotic tissues of columnar cacti of the Sonoran Desert, isolates from 39 organ pipe, 19 saguaro, and 16 senita cacti were obtained. The isolates were clustered into 28 conspecific groups on the basis of their fatty acid profiles. The distributions of the individual bacterial isolates varied among cactus species. Seven of the 28 species groups were unique to a particular cactus species, whereas 8 species groups were found in all three cacti. The effective number of bacterial species for each cactus species was positively correlated with both the chemical complexity and glucose concentration of the plant tissues. The effective number of bacterial species and bacterial distribution patterns were compared with those known for communities of cactophilic yeasts. The observed bacterial distribution patterns are most likely due to differences in the chemical compositions of the three cactus species. PMID- 8439143 TI - Arbitrary primer polymerase chain reaction, a powerful method to identify Bacillus thuringiensis serovars and strains. AB - Arbitrary primer polymerase chain reaction technology has been applied to the identification of commercial strains of Bacillus thuringiensis by using total DNAs extracted from single bacterial colonies as templates. Characteristic DNA banding patterns can be readily and reproducibly obtained by agarose gel electrophoresis. This method has been used to distinguish commercial products containing B. thuringiensis serovar kurstaki (3a3b). When a single primer was used this method was capable of producing discriminating DNA fingerprints for 33 known serovars. Differentiation from the closely related species Bacillus cereus is also readily achieved. This technique should prove to be a powerful tool for identification and discrimination of individual B. thuringiensis strains. PMID- 8439144 TI - Comparison of the post-Chernobyl 137Cs contamination of mushrooms from eastern Europe, Sweden, and North America. AB - A comparison was made of 134Cs and 137Cs contamination in fungi from eastern Europe and eastern North America. Mean activities of 25 Ukrainian, 6 Swedish, and 10 North American collections were 4,660, 9,750, and 205 Bq/kg (dry weight), respectively. Additional measurements were made on samples from the Moscow, southern Belarus, and Yugoslavia/Bulgaria regions. Activity values were found to vary by several orders of magnitude within all geographic areas, even for the same mushroom species. Significantly higher specific activities were observed in mycorrhizal species than in saprophytic and parasitic fungi. Unfortunately, many of the European mycorrhizal species considered as prized edibles contained unacceptably high levels of 137Cs (> 1,000 Bq/kg [dry weight]) and should be used sparingly as food. By contrast, no mushrooms collected in Ontario or northern Michigan exceeded 1,000 Bq of 137Cs per kg (dry weight). The excessive 137Cs contamination was evident in mushrooms from areas that had substantial fallout from the 1986 accident in reactor 4 at the Chernobyl nuclear power station. However, observations suggest that about 20% of the 137Cs in eastern Europe (Moscow area, Belarus, and Ukraine) is of non-Chernobyl origin. PMID- 8439145 TI - Identification and enumeration of Listeria monocytogenes by nonradioactive DNA probe colony hybridization. AB - A plasmid containing the cloned listeriolysin gene of Listeria monocytogenes was used as a probe to identify Listeria strains by DNA colony hybridization. The probe DNA was labeled with horseradish peroxidase in the presence of glutaraldehyde. After the hybridization and wash procedures, the hybrid molecules were detected by luminescence, which resulted from the oxidation of luminol by a horseradish peroxidase-hydrogen peroxide-coupled reaction. Of the 150 Listeria strains and 16 non-Listeria strains examined, the probe hybridized only with L. monocytogenes. The technique was also used to enumerate L. monocytogenes in artificially contaminated foods. PMID- 8439146 TI - Administration of different Lactobacillus strains in fermented oatmeal soup: in vivo colonization of human intestinal mucosa and effect on the indigenous flora. AB - In vivo colonization by different Lactobacillus strains on human intestinal mucosa of healthy volunteers was studied together with the effect of Lactobacillus administration on different groups of indigenous bacteria. A total of 19 test strains were administered in fermented oatmeal soup containing 5 x 10(6) CFU of each strain per ml by using a dose of 100 ml of soup per day for 10 days. Biopsies were taken from both the upper jejunum and the rectum 1 day before administration was started and 1 and 11 days after administration was terminated. The administration significantly increased the Lactobacillus counts on the jejunum mucosa, and high levels remained 11 days after administration was terminated. The levels of streptococci increased by 10- to 100-fold in two persons, and the levels of sulfite-reducing clostridia in the jejunum decreased by 10- to 100-fold in three of the volunteers 1 day after administration was terminated. In recta, the anaerobic bacterium counts and the gram-negative anaerobic bacterium counts decreased significantly by the end of administration. Furthermore, a decrease in the number of members of the Enterobacteriaceae by 1,000-fold was observed on the rectal mucosa of two persons. Randomly picked Lactobacillus isolates were identified phenotypically by API 50CH tests and genotypically by the plasmid profiles of strains and by restriction endonuclease analysis of chromosomal DNAs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8439147 TI - Cloning of the afl-2 gene involved in aflatoxin biosynthesis from Aspergillus flavus. AB - Aflatoxins are extremely potent carcinogens produced by Aspergillus flavus and Aspergillus parasiticus. Cloning of genes in the aflatoxin pathway provides a specific approach to understanding the regulation of aflatoxin biosynthesis and, subsequently, to the control of aflatoxin contamination of food and feed. This paper reports the isolation of a gene involved in aflatoxin biosynthesis by complementation of an aflatoxin-nonproducing mutant with a wild-type genomic cosmid library of A. flavus. Strain 650-33, blocked in aflatoxin biosynthesis at the afl-2 allele, was complemented by a 32-kb cosmid clone (B9), resulting in the production of aflatoxin. The onset and profile of aflatoxin accumulation was similar for the transformed strain and the wild-type strain (NRRL 3357) of the fungus, indicating that the integrated gene is under the same control as in wild type strains. Complementation analyses with DNA fragments from B9 indicated that the gene resides within a 2.2-kb fragment. Because this gene complements the mutated afl-2 allele, it was designated afl-2. Genetic evidence obtained from a double mutant showed that afl-2 is involved in aflatoxin biosynthesis before the formation of norsolorinic acid, the first stable intermediate identified in the pathway. Further, metabolite feeding studies with the mutant, transformed, and wild-type cultures and enzymatic activity measurements in cell extracts of these cultures suggest that afl-2 regulates gene expression or the activity of other aflatoxin pathway enzymes. This is the first reported isolation of a gene for aflatoxin biosynthesis in A. flavus. PMID- 8439148 TI - Adaptation and growth of Serratia marcescens in contact lens disinfectant solutions containing chlorhexidine gluconate. AB - Serratia marcescens (11 of 12 strains) demonstrated an ability to grow in certain chlorhexidine-based disinfecting solutions recommended for rigid gas-permeable contact lenses. For a representative strain, cells that were grown in nutrient rich medium, washed, and inoculated into disinfecting solution went into a nonrecoverable phase within 24 h. However, after 4 days, cells that had the ability to grow in the disinfectant (doubling time, g = 5.7 h) emerged. Solutions supporting growth of S. marcescens were filter sterilized. These solutions, even after removal of the cells, showed bactericidal activity against Pseudomonas aeruginosa and a biphasic survival curve when rechallenged with S. marcescens. Adaptation to chlorhexidine by S. marcescens was not observed in solutions formulated with borate ions. For chlorhexidine-adapted cells, the MIC of chlorhexidine in saline was eightfold higher than that for unadapted cells. Cells adapted to chlorhexidine showed alterations in the proteins of the outer membrane and increased adherence to polyethylene. Cells adapted to chlorhexidine persisted or grew in several other contact lens solutions with different antimicrobial agents, including benzalkonium chloride. PMID- 8439149 TI - Properties of nisin Z and distribution of its gene, nisZ, in Lactococcus lactis. AB - Two natural variants of the lantibiotic nisin that are produced by Lactococcus lactis are known. They have a similar structure but differ in a single amino acid residue at position 27; histidine in nisin A and asparagine in nisin Z (J.W.M. Mulders, I.J. Boerrigter, H.S. Rollema, R.J. Siezen, and W.M. de Vos, Eur. J. Biochem, 201:581-584, 1991). The nisin variants were purified to apparent homogeneity, and their biological activities were compared. Identical MICs of nisin A and nisin Z were found with all tested indicator strains of six different species of gram-positive bacteria. However, at concentrations above the MICs, with nisin Z the inhibition zones obtained in agar diffusion assays were invariably larger than those obtained with nisin A. This was observed with all tested indicator strains. These results suggest that nisin Z has better diffusion properties than nisin A in agar. The distribution of the nisin variants in various lactococcal strains was determined by amplification of the nisin structural gene by polymerase chain reaction followed by direct sequencing of the amplification product. In this way, it was established that the nisZ gene for nisin Z production is widely distributed, having been found in 14 of the 26 L. lactis strains analyzed. PMID- 8439150 TI - Monitoring airborne fungal spores in an experimental indoor environment to evaluate sampling methods and the effects of human activity on air sampling. AB - Aerobiological monitoring was conducted in an experimental room to aid in the development of standardized sampling protocols for airborne microorganisms in the indoor environment. The objectives of this research were to evaluate the relative efficiencies of selected sampling methods for the retrieval of airborne fungal spores and to determine the effect of human activity on air sampling. Dry aerosols containing known concentrations of Penicillium chrysogenum spores were generated, and air samples were taken by using Andersen six-stage, Surface Air System, Burkard, and depositional samplers. The Andersen and Burkard samplers retrieved the highest numbers of spores compared with the measurement standard, an aerodynamic particle sizer located inside the room. Data from paired samplers demonstrated that the Andersen sampler had the highest levels of sensitivity and repeatability. With a carpet as the source of P. chrysogenum spores, the effects of human activity (walking or vacuuming near the sampling site) on air sampling were also examined. Air samples were taken under undisturbed conditions and after human activity in the room. Human activity resulted in retrieval of significantly higher concentrations of airborne spores. Surface sampling of the carpet revealed moderate to heavy contamination despite relatively low airborne counts. Therefore, in certain situations, air sampling without concomitant surface sampling may not adequately reflect the level of microbial contamination in indoor environments. PMID- 8439151 TI - Characterization of the structural gene encoding a copper-containing nitrite reductase and homology of this gene to DNA of other denitrifiers. AB - A copper-containing nitrite reductase gene (nirU) from Pseudomonas sp. strain G 179 was found in a 1.9-kb EcoRI-BamHI DNA fragment. The coding region contained information for a polypeptide of 379 amino acids. The encoded protein had 78% identity in amino acid sequence to the nitrite reductase purified from Achromobacter cycloclastes. The ligands for type 1 copper- and type 2 copper binding sites found in A. cycloclastes were also found in Pseudomonas sp. strain G-179, suggesting that these binding sites are conserved. Upstream from the promoter, two putative fnr boxes were found, suggesting that an FNR-like protein may be involved in regulation of the nitrite reductase gene under anaerobic conditions. When the 1.9-kb clone was used to probe Southern blots for similar sequences in DNAs from different denitrifiers, hybridization bands were seen for 15 of 16 denitrifiers known to have nitrite reductase containing copper. Except for Pseudomonas stutzeri JM300, all denitrifiers tested that have nitrite reductases containing heme c,d1 showed no or weak hybridization to this probe. Thus, this structural gene may be useful as a probe to detect denitrifiers with copper-containing nitrite reductases. PMID- 8439152 TI - Presence of lactate dehydrogenase and lactate racemase in Megasphaera elsdenii grown on glucose or lactate. AB - Activity of D-lactate dehydrogenase (D-LDH) was shown not only in cell extracts from Megasphaera elsdenii grown on DL-lactate, but also in cell extracts from glucose-grown cells, although glucose-grown cells contained approximately half as much D-LDH as DL-lactate-grown cells. This indicates that the D-LDH of M. elsdenii is a constitutive enzyme. However, lactate racemase (LR) activity was present in DL-lactate-grown cells, but was not detected in glucose-grown cells, suggesting that LR is induced by lactate. Acetate, propionate, and butyrate were produced similarly from both D- and L-lactate, indicating that LR can be induced by both D- and L-lactate. These results suggest that the primary reason for the inability of M. elsdenii to produce propionate from glucose is that cells fermenting glucose do not synthesize LR, which is induced by lactate. PMID- 8439153 TI - Molecular analysis of the rolling-circle replicating plasmid pA1 of Lactobacillus plantarum A112. AB - Lactobacillus plantarum A112 has four different plasmids. Plus-origin-specific probes were used to determine that the smallest, cryptic plasmid, pA1 (2,820 bp), showed homology to the pE194 plasmid family. This subclass of plasmids uses the rolling-circle mode of replication. Subsequent analysis of plasmid pA1 demonstrated that it generates single-stranded DNA intermediates, and sequence analysis revealed that it contains three putative open reading frames (ORFs): ORF1, ORF2, and ORF3, which could encode proteins designated RepA (47 amino acids [aa]) and RepB (196 aa) and a protein of 103 aa, respectively. Two of these proteins, RepA (5.6 kDa) and RepB (26 kDa), were identified in in vitro transcription translation assays. The RepA protein contains a characteristic alpha-helix-turn-alpha-helix motif typical of DNA-binding proteins that act as DNA-binding repressors. The RepB protein shows a significant similarity with replication initiation proteins of the pE194 family of plasmids that use the rolling-circle mode of replication. Plasmid pA1 is able to replicate in Escherichia coli and Lactobacillus lactis subsp. lactis as well as in other L. plantarum strains. PMID- 8439154 TI - Microbial degradation of dibenzofuran, fluorene, and dibenzo-p-dioxin by Staphylococcus auriculans DBF63. AB - Staphylococcus auriculans DBF63, which can grow on dibenzofuran (DBF) or fluorene (FN) as the sole source of carbon and energy, was isolated. Salicylic acid and gentisic acid accumulated in the culture broth of this strain when DBF was supplied as a growth substrate. Also, the formation of 9-fluorenol, 9-fluorenone, 4-hydroxy-9-fluorenone, and 1-hydroxy-9-fluorenone was demonstrated, and accumulation of 1,1a-dihydroxy-1-hydro-9-fluorenone was observed when this strain grew on FN. On the basis of these results, the degradation pathways of DBF and FN were proposed. The analogous oxidation products of dibenzo-p-dioxin were obtained by incubation with DBF-grown S. auriculans DBF63 cells. PMID- 8439155 TI - Cobalamin-mediated mercury methylation by Desulfovibrio desulfuricans LS. AB - The prominence of sulfate reducers in mercury biomethylation prompted the examination of the methyl carrier and mercury methylation activity of Desulfovibrio desulfuricans LS. There was a low degree of mercury tolerance and a high degree of methylation during fermentative growth; the opposite was true during sulfate reduction. During 2 days of fermentative growth, up to 37% of HgCl2 was methylated at 0.1 micrograms/ml, but only 1.5% was methylated at 10.0 micrograms/ml. Less than 1% of the added HgCl2 was methylated under sulfate reducing conditions. D. desulfuricans LS radioimmunoassay results were positive for cobalamin. The addition of CoCl2 and benzimidazole to fermentative cultures increased methylation activity. From D. desulfuricans LS grown in the presence of (57)CoCl2, a corrinoid was extracted and purified. High-performance liquid chromatography analysis of the purified extract yielded a single peak with the retention time of cobalamin, and 97% of the (57)Co radioactivity was associated with this peak. Fast atom bombardment and UV and visible spectra of the isolated corrinoid matched those of cobalamin. When methylated with (14)CH3I, the isolated corrinoid methylated Hg(2+) with a 93.9% preservation of (14)C specific activity. We conclude that D. desulfuricans LS methylates mercury via cobalamin (vitamin B12). Under physiological conditions, the enzymatic catalysis of this reaction is likely. PMID- 8439156 TI - Biosynthesis of the lantibiotic subtilin is regulated by a histidine kinase/response regulator system. AB - Subtilin is a lanthionine-containing peptide antibiotic (lantibiotic) which is produced by Bacillus subtilis ATCC 6633. Upstream from the structural gene of subtilin, spaS, three genes (spaB, spaT, and spaC) which are involved in the biosynthesis of subtilin have been identified (C. Klein, C. Kaletta, N. Schnell, and K.-D. Entian, Appl. Environ. Microbiol. 58:132-142, 1992). By using a hybridization probe specific for these genes, the DNA region downstream from spaS was isolated. Further subcloning revealed a 5.2-kb KpnI-HindIII fragment on which two open reading frames, spaR and spaK, were identified approximately 3 kb downstream from spaS. The spaR gene encodes an open reading frame of 220 amino acids with a predicted molecular mass of 25.6 kDa. SpaR shows 35% similarity to positive regulatory factors OmpR and PhoB. The spaK gene encodes an open reading frame of 387 amino acids with a predicted molecular mass of 44.6 kDa and was highly similar to histidine kinases previously described (PhoM, PhoR, and NtrB). Hydrophobicity blots suggested two membrane-spanning regions. Thus, spaR and spaK belong to a recently identified family of environmentally responsive regulators. These results indicated a regulatory function of spaR and spaK in subtilin biosynthesis. Indeed, batch culture experiments confirmed the regulation of subtilin biosynthesis starting in the mid-logarithmic growth phase and reaching its maximum in the early stationary growth phase. Gene deletions within spaR and spaK yielded subtilin-negative mutants, which confirms that subtilin biosynthesis is under the control of a two-component regulatory system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8439157 TI - Differentiation of Listeria monocytogenes and Listeria innocua by 16S rRNA genes and intraspecies discrimination of Listeria monocytogenes strains by random amplified polymorphic DNA polymorphisms. AB - Differences in the 16S rRNA genes (16S rDNA) which can be used to discriminate Listeria monocytogenes from Listeria innocua have been detected. The 16S rDNA were amplified by polymerase chain reaction with a set of oligonucleotide primers which flank a 1.5-kb fragment. Sequence differences were observed in the V2 region of the 16S rDNA both between L. monocytogenes Scott A and L. innocua and between different L. monocytogenes serotypes. Although L. monocytogenes SLCC2371 had the same V2 region sequence as L. innocua, the two species were different within the V9 region at nucleotides 1259 and 1292, in agreement with previous studies (R.-F. Wang, W.-W. Cao, and M.G. Johnson, Appl. Environ. Microbiol. 57:3666-3670, 1991). Intraspecies discrimination of L. monocytogenes strains was achieved by using the patterns generated by random amplified polymorphic DNA primers. Although some distinction can be made within the L. monocytogenes species by their 16S rDNA sequence, a far greater discrimination within species could be made by generating random amplified polymorphic DNA patterns from chromosomal DNA. By using a number of 10-bp primers, unique patterns for each isolate which in all cases examined differentiate between various L. monocytogenes serotypes, even though they may have the same 16S rRNA sequences, could be generated. PMID- 8439158 TI - Chromosomal rearrangements during vegetative growth of a wild strain of Saccharomyces cerevisiae. AB - Electrophoretic karyotypes of two strains of Saccharomyces cerevisiae, a haploid laboratory strain and a wild strain known to be at least diploid, have been checked during vegetative growth. The karyotype of the haploid strain was very stable; however, the diploid strain underwent frequent modifications. In most cases the number of bands was reduced, but occasionally we observed one band splitting into two. In one case, chromosomal rearrangements took place between differently sized copies of chromosomes I and VI. We concluded that the chromosome length polymorphism observed among wild strains of S. cerevisiae could be explained partly by chromosomal structure reorganization occurring during mitosis. PMID- 8439159 TI - Quantitative observations of heterogeneities in Pseudomonas aeruginosa biofilms. AB - Heterogeneity in a Pseudomonas aeruginosa biofilm was quantified by measuring distributions of thickness in biofilm samples and a distribution of particle sizes in effluent samples. The mean steady-state thickness was approximately 33 microns, but individual measurements ranged from 13.3 to 60.0 microns. Particles exceeding 100 microns3 were observed in the reactor effluent. The results reveal a rough biofilm surface and indicate that most biomass detaches in the form of multicellular particles. PMID- 8439160 TI - Cloning and sequencing of pepC, a cysteine aminopeptidase gene from Lactococcus lactis subsp. cremoris AM2. AB - A gene coding for an aminopeptidase (PepC) from Lactococcus lactis subsp. cremoris AM2 was cloned by complementation of an Escherichia coli mutant lacking aminopeptidase activity. The nucleotide sequence was determined. A portion of the predicted amino acid sequence of PepC (436 amino acids) showed strong homology to the active site of cysteine proteases. No signal sequence was found, indicating an intracellular location of the enzyme. PMID- 8439161 TI - Construction and characterization of heavy metal-resistant haloaromatic-degrading Alcaligenes eutrophus strains. AB - Alcaligenes eutrophus strains exhibiting both plasmid-borne heavy metal resistance and haloaromatic-degrading functions were obtained by intraspecific conjugation. The strains which we constructed expressed catabolic and resistance markers together. Degradation of various polychlorinated biphenyl isomers and 2,4 D (2,4-dichlorophenoxyacetic acid) was observed in the presence of 1 mM nickel or 2 mM zinc, provided that the metal resistance determinant was present in the catabolizing strain. Such strains may be useful for decontamination of sites that are polluted with both organic compounds and heavy metals. PMID- 8439162 TI - Inhibition of adhesion of Escherichia coli K88 to piglet ileal mucus by Lactobacillus spp. AB - Enteropathogenic Escherichia coli K88 colonizing the piglet ileum adhere to the mucosa by K88 fimbrial appendages. A recent study in our laboratory has implicated indigenous lactobacilli in the suppression of the colonization potential of enteropathogenic E. coli as measured by adhesion to ileal mucus. The aim of this study was to investigate the effect of Lactobacillus spp. of porcine origin on the adhesion of K88 fimbriae of E. coli. With an in vitro assay, the adhesion of E. coli K88ab strain G1108E and E. coli K88ac strain 1107 to 35-day old piglet ileal mucus was studied in the presence of spent culture fluid of Lactobacillus spp. Detailed studies focused specifically on culture fluid of Lactobacillus fermentum 104R. Subsequently, the ileal mucus was exposed to the retentate of the spent culture fluid after dialysis and fractionation. Adhesion was confirmed to be attributable to K88 fimbriae when K88-specific monoclonal antibodies and isogenic mutants of E. coli K-12 with and without the plasmid containing the K88 gene were used. The active component was characterized by pretreatment of dialysis retentate with heat, periodate, pronase, and centrifugation, as well as by growth of the lactobacillus in various media and by assays at both 0 and 37 degrees C. All three lactobacilli of porcine origin reduced adhesion of E. coli K88 by approximately 50%. Inhibition occurred when mucus was pretreated with either spent culture dialysis retentate or the void volume (fraction of > 250,000 molecular weight) after gel filtration. The activity of the dialysis retentate was sensitive to pronase, but there was still activity at 0 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8439163 TI - Starvation-survival of a p-nitrophenol-degrading bacterium. AB - An environmental actinomycetes, capable of utilizing p-nitrophenol as its sole carbon and nitrogen source, was starved for an 8-week period and showed no reduction in its ability to biodegrade p-nitrophenol. Microscopic examination revealed that starvation of the bacterium resulted in the fragmentation of filaments into individual cells. PMID- 8439164 TI - Comparison of membrane filters for recovery of legionellae from water samples. AB - The procedure currently used for isolating legionellae from environmental samples recommend filtration through a 0.2-microns-pore-size polycarbonate filter. In this study we evaluated the performance of 23 other filters composed of various materials and having various pore sizes. We prefer the 0.2-micron-pore-size Gelman Supor filter because of its high level of recovery, faster filtration rate, and ease of handling. PMID- 8439165 TI - Cloning and characterization of the gene encoding glutamate 1-semialdehyde 2,1 aminomutase, which is involved in delta-aminolevulinic acid synthesis in Propionibacterium freudenreichii. AB - The gene from Propionibacterium freudenreichii that encodes glutamate 1 semialdehyde 2,1-aminomutase (EC 5.4.3.8), which is involved in the C5 pathway for synthesis of delta-aminolevulinic acid (ALA), a precursor in heme and cobalamin biosynthesis, was cloned onto a multicopy plasmid, pUC18, via complementation of an ALA-deficient mutant (hemL) of Escherichia coli. Subcloning of fragments from the initial 3.3-kb chromosomal fragment allowed the isolation of a 1.9-kb fragment which could complement the hemL mutation. Nucleotide sequence analysis of the 1.9-kb DNA fragment revealed an open reading frame (ORF) that was located downstream from a potential ribosome-binding site. The ORF encoded a polypeptide of 441 amino acid residues, and the deduced molecular mass of this polypeptide is 45,932 Da. A high G+C content (70 mol%) of the codons of the ORF was found and was consistent with the taxonomic features of Propionibacterium species. The amino acid sequence showed a high degree of homology with those of the HemL proteins from other organisms, and a putative binding site for pyridoxal 5'-phosphate was conserved, with the exception of a single substitution of phenylalanine for leucine. These results suggest that ALA is synthesized via the C5 pathway in a producer of vitamin B12, P. freudenreichii. PMID- 8439166 TI - Evidence for catabolite inhibition in regulation of pentose utilization and transport in the ruminal bacterium Selenomonas ruminantium. AB - Pentose sugars can be an important energy source for ruminal bacteria, but there has been relatively little study regarding the regulation of pentose utilization and transport by these organisms. Selenomonas ruminantium, a prevalent ruminal bacterium, actively metabolizes xylose and arabinose. When strain D was incubated with a combination of glucose and xylose or arabinose, the hexose was preferentially utilized over pentoses, and similar preferences were observed for sucrose and maltose. However, there was simultaneous utilization of cellobiose and pentoses. Continuous-culture studies indicated that at a low dilution rate (0.10 h-1) the organism was able to co-utilize glucose and xylose. This co utilization was associated with growth rate-dependent decreases in glucose phosphotransferase activity, and it appeared that inhibition of pentose utilization was due to catabolite inhibition by the glucose phosphotransferase transport system. Xylose transport activity in strain D required induction, while arabinose permease synthesis did not require inducer but was subject to repression by glucose. Since an electrical potential or a chemical gradient of protons drove xylose and arabinose uptake, pentose-proton symport systems apparently contributed to transport. PMID- 8439167 TI - Growth, copper-tolerant cells, and extracellular protein production in copper stressed chemostat cultures of Vibrio alginolyticus. AB - The influence of elevated copper concentrations on cell numbers and extracellular protein production was investigated in chemostat cultures of Vibrio alginolyticus. High (20 microM) copper in the medium reservoir resulted in a dramatic drop in cell numbers which was overcome with time. The copper-stressed cultures established a new equilibrium cell concentration slightly (ca. 20%) lower than control cultures. Copper-stressed chemostat populations contained an increased number of copper-resistant cells, but these averaged only 26% of the copper-adapted population. Previously copper-stressed populations exhibited resistance to a second challenge with copper. Proteins with properties identical to those of copper-induced, copper-binding proteins (CuBPs) observed in batch cultures of V. alginolyticus were observed in the supernatants of copper-stressed chemostat cultures and not in controls. CuBPs from batch and chemostat cultures were identical in terms of their induction by copper, molecular weight, and retention volumes on both immobilized copper ion-affinity chromatography and reverse-phase high-performance liquid chromatography columns. The concentration of CuBP in the chemostat was dependent on copper concentration in the medium reservoir. Either one or two forms of CuBP were observed in various analyses from both batch and chemostat cultures. Gel-to-gel variability was implicated as a factor determining whether one or two forms were resolved in a given analysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8439168 TI - Waterborne Giardia cysts and Cryptosporidium oocysts in the Yukon, Canada. AB - Several outbreaks of waterborne giardiasis have occurred in southern Canada, but nothing has been reported from the Canadian North. The objective of this study was to collect information relevant to waterborne giardiasis and cryptosporidiosis in the Yukon including epidemiological data and analyses of water, sewage, and animal fecal samples. Remote, pristine water samples were found to be contaminated with Giardia cysts (7 of 22 or 32%) but not with Cryptosporidium oocysts. Giardia cysts were found in 21% (13 of 61) of animal scats, but no Cryptosporidium oocysts were observed (small sample size). Whitehorse's drinking water was episodically contaminated with Giardia cysts (7 of 42 or 17%) and Cryptosporidium oocysts (2 of 42 or 5%). Neither were found in Dawson City's water supply. The only water treatment in the Yukon is chlorination, but contact times and free chlorine residuals are often too low to provide adequate protection by disinfection. Raw sewage samples from the five largest population centers in the Yukon contained 26 to 3,022 Giardia cysts and 0 to 74 Cryptosporidium oocysts per liter. Treated sewage from Whitehorse contained fewer Giardia cysts but more Cryptosporidium oocysts on average. Both were detected in Lake Laberge, downstream of Whitehorse, which has a history of fecal coliform contamination. Daily monitoring of raw sewage from the suburbs of Whitehorse showed a summertime peak of Giardia cysts and occasional Cryptosporidium oocysts after springtime contamination of drinking water. Despite this evidence, epidemiological data for the Yukon showed an endemic infection rate of only 0.1% for giardiasis (cryptosporidiosis is not notifiable).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8439169 TI - Precipitation of cadmium by Clostridium thermoaceticum. AB - Cadmium at an initial concentration of 1 mM was completely precipitated by cultures of Clostridium thermoaceticum in complex medium. The precipitation was energy dependent and required cysteine, although cysteine alone did not act as a growth substrate. Electron microscopic analysis revealed localized areas of precipitation at the surfaces of nonstarved cells as well as precipitate in the surrounding medium. The addition of cadmium had no apparent effect on growth or acetogenesis. However, nickel and cadmium were synergistically toxic at a concentration (1 mM) at which neither alone was toxic. The amount of protein extracted from cadmium-treated cultures was twofold higher than that in control extracts, and the amount of total sulfide was fourfold higher in cultures containing cadmium than in control cultures. Comparable levels of cysteine desulfhydrase activity were observed in extracts of both cadmium-treated and control cultures, but the enzyme activity was expressed maximally about 24 h earlier in the cadmium-treated cultures than in the untreated controls. PMID- 8439170 TI - Isolation and purification of propionicin PLG-1, a bacteriocin produced by a strain of Propionibacterium thoenii. AB - Production of propionicin PLG-1 by Propionibacterium thoenii P127 was pH dependent, with maximal activity detected in supernatants of cultures grown at pH 7.0 Propionicin PLG-1 was purified by ion-exchange chromatography and isoelectric focusing. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of propionicin PLG-1 purified through isoelectric focusing resolved a protein band with a molecular weight of 10,000. Propionicin PLG-1 was bactericidal to sensitive cells, demonstrating single-hit kinetics. The producing strain harbored a single plasmid (pLG1) with an approximate size of 250 kb. Preliminary data indicate that both propionicin PLG-1 and immunity to the bacteriocin are encoded on the chromosome. Exposure of strain P127 to acriflavine or to N-methyl-N'-nitro N-nitrosoguanidine yielded isolates that no longer produced bacteriocin activity and isolates that were cured of the plasmid. However, loss of bacteriocin production was not correlated with loss of the plasmid. Isolates cured of the plasmid were phenotypically identical to plasmid-bearing cells in fermentation patterns, pigment production, and growth characteristics. PMID- 8439171 TI - Characterization of the genome of the Rhodococcus rhodochrous bacteriophage NJL. AB - Temperate bacteriophage NJL of Rhodococcus rhodochrous has a 49-kb linear double stranded DNA with cohesive ends (cos). NJL DNA has unique target sites for HindIII and SspI, two target sites each for NheI and ScaI, and no cleavage site for AxyI, DraI, EcoRI, SacI, and SphI. The single-stranded regions of cos ends were ligated to each other with T4 DNA ligase, removed with mung bean nuclease, or blunted with the Klenow large fragment of DNA polymerase I; then the sequences of the cos ends were determined. Comparison of these sequences revealed that the single-stranded regions are complementary and 18 bases long and protrude at the 3' ends; they have the following sequences: 5'-TTGGCACCGTGGGAGGAG-3' and 3' AACCGTGGCAC CCTCCTC-5'. A physical map of NJL was constructed by a cos mapping method based on information about the structure of the cohesive ends and multiple digestions with restriction endonucleases. PMID- 8439172 TI - Variables affecting the reporting of pain following an acute myocardial infarction. AB - The presence of unreported chest pain (CP) in patients hospitalized with an acute myocardial infarction (AMI) has received only anecdotal mention in the literature, with the exception of one small study. A purposeful sample of seven informants, using an exploratory design and qualitative methods, was used to examine the experience and reporting of CP. The data indicated existence of unreported CP and represented a process of decision-making in response to the symptoms associated with an AMI. The decision-making process involved three stages: the experience of pain, assessing the pain, and taking action. The reporting of pain (or failure to report pain) was found to be influenced by a broad range of internal and external cues that occurred throughout the decision making process. PMID- 8439173 TI - Content analysis of groups for inpatients with bipolar disorder. AB - Group therapy for patients with bipolar disorder is recognized as beneficial but has not been studied in an inpatient population. In this study, content analysis procedures were used to describe the content and process issues in 40 short-term group psychotherapy sessions attended by 65 inpatients with bipolar disorder. Five core categories emerged from the content: understanding the disorder, relating with others, managing daily life, relating with self, and living in society. Guidance, universality, and self-understanding were described most frequently when patients identified the group event that was most personally important to them. Implications for practice include providing therapy and education to this population through a topic-oriented group model. PMID- 8439174 TI - Predictors of concerns and coping strategies of cancer chemotherapy outpatients. AB - The purpose of this study was to determine predictor variables of the number of concerns and coping strategies of cancer patients during a 6-month period of chemotherapy. The adult patients (N = 64) were diagnosed with selected types of cancer. Patients kept logs in which they recorded concerns and strategies for managing those concerns. Three significant predictors of patients who experienced greater numbers of concerns were identified. Patients with less vigor-activity, less of an internal locus of control, and who perceived the goal of their chemotherapy treatment to be curative reported greater concerns. These factors explained 55% of the total variance in the number of concerns. No significant predictors of coping strategies were obtained. PMID- 8439175 TI - Older adults' metamemory: coping, depression and self-efficacy. PMID- 8439176 TI - The parenting profile assessment: screening for child abuse. PMID- 8439177 TI - Comparison of selected pain assessment tools for use with the elderly. PMID- 8439178 TI - Applying triangulation in nursing research. PMID- 8439179 TI - Acoustical analysis of maternal sounds during the second stage of labor. AB - Experienced obstetric nurse and midwives indicate they can differentiate among sounds indicating that a woman is (a) beginning to manifest the effort to bear down, (b) experiencing pain, or (c) frightened. This study examined the acoustical properties of work/effort, childlike, and out-of-control utterances to determine whether their acoustical properties differed. Out-of-control utterances are more tense but contain similar levels of shimmer and pitch as childlike utterances. Work/effort utterances are higher pitched and more tense than childlike utterances. Work/effort utterances contain more shimmer but have similar levels of pitch and tenseness as out-of-control utterances. PMID- 8439180 TI - [Regulation of cadherin-based cell adhesion and metastasis]. AB - Cadherins are a family of transmembrane glycoproteins which are responsible for calcium-dependent cell-cell adhesion. At least two types of proteins called alpha and beta-catenin are known to be closely associated with the cytoplasmic domain of cadherin molecules and to play a crucial role in the regulation of cadherin cell adhesion function. Sequence analyses of cDNAs encoding these catenins have revealed that alpha- and beta-catenins have a similarity to vinculin and Drosophila armadillo protein, respectively. The possible involvement of these catenin molecules in the molecular mechanism of human cancer invasion and metastasis is discussed. PMID- 8439181 TI - [Visualization of phosphorylation events occurring in the intermediate filaments]. AB - Glial fibrillary acidic protein (GFAP) is a component of glial filaments specific to astroglia. We now report the spatial and temporal distributions of four phosphorylated sites in the GFAP molecule during mitosis of astroglial cells, determined by antibodies which can distinguish phosphorylated-epitopes from non phosphorylated-epitopes. Immunofluorescence microscopy showed that the Ser-8 residues in the entire cytoplasmic glial filament system are initially phosphorylated when the cells enter mitosis. In cytokinesis, the phospho Ser-8 residues become dephosphorylated, whereas Thr-7, Ser-13 and Ser-34 in glial filaments at the cleavage furrow become the preferred sites of phosphorylation. These results suggest that multiple glial filament kinases are activated with different time schedules in astroglial cells. PMID- 8439182 TI - [Tumor metastasis and adhesion molecules]. AB - Effective prevention of tumor metastasis would be a great contribution to the therapy of malignant tumors. Recent progress in the research of adhesion molecules has revealed that cell adhesion is an essential process in tumor metastasis. In this study, we discuss the possible involvement of adhesion molecules in various steps of tumor metastasis. PMID- 8439183 TI - [Inhibition of tumor cell adhesion and metastasis]. AB - Since the establishment of an experimental metastasis model using some tumor metastatic cell lines, progress has been made in basic studies on tumor metastasis. In addition, the complex mechanisms of tumor metastasis have been elucidated by the cellular and molecular studies. Here we focus our attention on the relationship between tumor metastasis and cellular adhesiveness, a factor which is a critical determinant in tumor progression and metastasis. The roles of cell adhesive molecules in the metastatic process are also described. This type of study is invaluable in understanding the molecular and regulatory mechanisms of tumor metastasis. We also report the antimetastatic effect of some polypeptides of fibronectin in the extracellular matrices, poly (RGD) and recombinant fusion peptide containing cell- and heparin-binding domain of fibronectin (CH-271) in regulating the mechanism of tumor cell adhesion. PMID- 8439184 TI - [Regulation of tumor metastasis and extracellular matrix degradative enzyme production by microenvironments]. AB - We have recently established human tumor cell lines which metastasize to specific organs from orthotopic implantation sites but not from ectopic sites in nude mice. Using these tumor cell lines we have been studying the mechanisms of the regulation of tumor metastasis by organ specific microenvironments. Here, we discuss the mechanisms of the regulation of extracellular matrix degrading enzyme production by interactions between tumor cells and tissue specific fibroblasts. PMID- 8439185 TI - [Expression of matrix metalloproteinases in tumor cells]. AB - Tumor cells have to degrade extracellular matrix components to invade surrounding tissue and to form metastatic colonies at distant organs. Matrix metalloproteinases are the enzymes that can degrade various types of native collagens and glycoproteins. In this study, we demonstrated the roles of matrix metalloproteinases in metastatic colony formation in chick embryo by transfecting TIMP-1 gene into a metastatic gastric cancer cell line, KKLS. The mechanism regulating expression of one of the type IV collagenases, MMP-9, was also studied using the promoter region of the gene. PMID- 8439186 TI - [Lymphatic metastasis and cell adhesion, growth and growth inhibition]. AB - Malignant tumor cells often metastasize to regional and distant lymph nodes. The mechanisms of lymphatic metastasis, however, have not been well understood. To investigate these mechanisms, we used mouse CS-21 malignant T lymphoma cells which form tumors at subcutaneous sites and metastasize to lymph nodes with a high incidence. In contrast, CS-21 cells do not metastasize to other organs following intravenous injection. CS-21 lymphoma cells continuously grew in vitro when the cells were cocultured with CA-12 stromal cells isolated from lymph nodes. However, when CS-21 cells were separated from the stromal cells, they underwent apoptosis which was characterized by nucleus condensation and DNA fragmentation. We have developed monoclonal antibodies against CS-21 cell surface molecules by intrasplenic injection of the cell membranes. Several clones of monoclonal antibodies were able to partially inhibit adhesion of CS-21 cells to a monolayer of CA-12 stromal cells. Treatment of CS-21 cells with the monoclonal antibodies which specifically bind to the cell surface components of M(r) -168K and -23K prevented the apoptosis of CS-21 cells after separation from the stromal cells. In the experiments using Transwell chambers we found that the growth of CS 21 cells was also supported by soluble factors secreted from CA-12 stromal cells. The secreted factors were, however, not sufficient to prevent CS-21 cell apoptosis. The result suggested that the stromal cells of lymph nodes play an important role in lymphatic metastasis of CS-21 lymphoma cells by cell-cell adhesion and secretion of soluble factors that prevent apoptosis of lymphoma cells and enhance their growth in concert. PMID- 8439187 TI - [Scatter factor and cell motility]. AB - Cell dispersion and motility are thought to be important steps in the invasion of tumor cells. The molecular mechanisms responsible for the induction of cell dispersion and motility remain unclear. Several factors affecting cell motility have been discovered. Among them, scatter factor (SF), a mesenchymal cell-derived protein, dissociates epithelial cell colonies into individual cells and stimulates the migration of epithelial cells. Purified SF promotes the invasiveness into collagen matrices of a number of human carcinoma cell lines, suggesting that SF is involved in the invasion of tumor cells. Recently, SF has been found to be identical to hepatocyte growth factor. Moreover, the c-met proto oncogene product (the c-met protein) possessing a tyrosine kinase domain was identified as a receptor for SF. Three possible mechanisms have been postulated in which a tumor cell might increase its invasive potential through enhanced motility via SF and its receptor. First, in a cell already expressing the c-met protein, an unexpressed SF gene might be activated, leading to synthesis and secretion of the factor which could then initiate active motility in an autocrine fashion. Second, the tumor cell expressing the c-met protein may release a factor that affects surrounding mesenchymal cells, promotes synthesis and release of SF. The tumor cell would be stimulated in a paracrine fashion. Finally, the tumor cell may be exposed to SF already released by surrounding cells but may not be able to respond because it is partially or completely deficient in the c-met protein. Induction and increased expression of the c-met gene would result in the invasive phenotype of the tumor cell. Studies on these possible mechanisms will be required to elucidate the involvement of SF in the invasion of tumor cells. PMID- 8439188 TI - [Enhanced malignancy of tumor cells by the interaction with host cells reactive to foreign body]. AB - We examined factors promoting malignant progression using a weakly malignant variant cell line, ER-1, derived from c-SST-2, a rat mammary carcinoma. ER-1 cells were converted to a highly malignant phenotype (highly tumorigenic, metastatic, invasive in vitro) by the in vitro/in vivo interaction with host cells reactive to foreign body. Epidermal growth factor (EGF) and transforming growth factor-beta (TGF-beta) produced by host reactive cells, transiently enhanced the tumorigenicity and in vitro invasiveness of ER-1 cells into an endothelial cell monolayer. The host reactive cells also produced oxygen radicals and induced mutations in ER-1 cells. It is speculated that mutations induced by host reactive cells cause cellular diversification, including the emergence of highly malignant variant cells whose growth is selectively promoted by growth factors such as EGF and TGF-beta. PMID- 8439189 TI - Pulmonary gas exchange during facemask ventilation immediately after birth. AB - The rate of carbon dioxide production (VCO2), heart rate, and oxygen saturation were recorded during resuscitation in 30 newborn infants. Twenty eight infants were ventilated through a facemask only and two were intubated after initial facemask ventilation. Five neonates were born at full term, eight had a gestational age of 32-36 weeks, and 17 of 27-31 weeks. Towards the end of the five minute study period, the VCO2 in ventilated infants, born after 32 weeks or more, was not different from that of spontaneously breathing infants. Neonates with a gestational age of 27-31 weeks showed a low VCO2, particularly when no reflex response from the baby was recorded, with a significant increase if a reflex response was elicited. Ventilation was found to be satisfactory if the heart rate increased to 130 beats/min or more within 5-15 seconds or if the oxygen saturation, measured in the right hand, was 70% or more. PMID- 8439190 TI - Echocardiographic assessment of cardiac function in shocked very low birthweight infants. AB - The contribution of abnormal cardiac function to hypotension and metabolic acidosis, which affect approximately 40% of ventilated very low birthweight infants in the first 24 hours after birth was assessed using M mode, two dimensional, and Doppler echocardiography in 75 very low birthweight infants during the first few hours after birth. Thirty four infants whose blood pressure was less than the 10th centile or who had a metabolic acidosis in the first 24 hours were compared with 41 who showed neither feature. The median shortening fraction was significantly lower in the hypotensive/acidotic (shocked) group than in the controls. In 16 of 34 (47%) shocked infants left ventricular contractility and output were significantly worse than in the control subjects. One and five minute Apgar scores were also significantly lower in the shock group when compared with controls. Cardiac dysfunction was an important feature in the shocked very low birthweight infants. It is speculated that volume expansion may not always be the most appropriate first line treatment for such infants. PMID- 8439191 TI - Urological anomalies in the Northern Region Fetal Abnormality Survey. AB - From 1 January 1985 to 31 December 1990, the Northern Region Fetal Abnormality Survey received 736 notifications of fetuses with suspected urological abnormalities; a prevalence of three per 1000 births. There was a male:female ratio of 2:1, the ratio was higher in obstructive than in intrinsic renal parenchymal lesions. Overall diagnostic sensitivity was 68.9% and positive predictive value 50.8%. Hydronephrosis was the most frequent antenatal diagnosis (421 cases, 57.2%): 233 (55.3%) of these were found to be normal postnatally. There were 52 other false positive diagnoses. Of 113 babies with confirmed hydronephrosis antenatal diagnosis was correct in 97, sensitivity 85.8%, specificity 48.1%; 1.8% of these had chromosome defects. In 33 cases of bilateral renal agenesis antenatal diagnosis was correct or potentially correct in 24, sensitivity 72.7%, specificity 98.9%. Only six of 26 babies with posterior urethral valves were suspected, sensitivity 23%, specificity 98.7%. Mortality rate in 91 babies with unsuspected abnormalities was 39.6%: overall mortality was 24.2%. Unsuspected abnormalities occurred more frequently when mothers were not scanned after the 16th week of pregnancy. PMID- 8439192 TI - Transcutaneous application of oil and prevention of essential fatty acid deficiency in preterm infants. AB - The topical application of vegetable oil was assessed as an alternative means of providing essential fatty acids (EFA) to parentally fed preterm infants who were not receiving lipid. Three infant pairs ranging in gestational age from 26-32 weeks were studied. Safflower oil or safflower oil esters (1 g linoleic acid/kg/day) were applied to available areas daily. All infants rapidly developed biochemical EFA deficiency. The plasma fatty acid profiles were similar in infants with or without topical oil, and all returned to normal once parenteral lipid was introduced. We found no evidence to suggest that the transdermal route is of use in the nutritional management of preterm infants. PMID- 8439194 TI - Screening for toxoplasmosis during pregnancy. PMID- 8439193 TI - Changes in plasma cortisol and catecholamine concentrations in response to massage in preterm infants. AB - The biochemical and clinical response to massage in preterm infants was assessed. Eleven stable infants, of 29 weeks' median gestational age, median birth weight 980 g, and median postnatal age 20 days, were studied. Blood samples were obtained for the determination of adrenaline, noradrenaline, and cortisol 45 minutes before the start of massage and approximately one hour after completion of massage. Cortisol, but not catecholamine, concentrations decreased consistently after massage (median difference -35.8 nmol/l; 95% confidence interval -0.5 to -94.0, Wilcoxon matched pairs). There was a slight decrease in skin temperature (median difference -0.36 degrees C, 95% confidence interval 0.09 to -0.65) but there was no change in oxygenation or oxygen requirement. This study has shown that it is possible to detect an objective hormonal change following a supposedly 'non-therapeutic' intervention in preterm infants. The development of such methods of assessment are likely to be of particular relevance in the extremely immature or ill neonate in whom behavioural evaluation cannot play more than a limited part. PMID- 8439195 TI - Biased assessment of gestational age at birth when obstetric gestation is known. AB - The gestational age of 302 neonates whose obstetric gestational age was known was assessed at birth using the Dubowitz method; it was obtained from Dubowitz score both graphically from a nomogram and by calculation from the corresponding equation. The values obtained graphically differed to a lesser extent from the obstetric gestational age than did the gestation derived algebraically. With infants small for gestational age (SGA) the difference between the methods was smaller and not significant. It is concluded that the concurrent knowledge of obstetric gestational age introduced a bias in the graphic step; this did not happen in SGA infants probably because in these cases the available information is sometimes less certain. These data demonstrate that even simple procedures are influenced by concurrent information; as a philosophical point about the interpretation of data in general, this study provides an empirical example of the 'theory-ladenness of facts' in medicine. PMID- 8439196 TI - Fetal anaemia and its relation with increased concentrations of adenosine. AB - Adenosine concentrations were measured in umbilical venous blood obtained by cordocentesis from 14 fetuses of 19-34 weeks' gestation. The concentration did not change significantly with gestational age, but anaemic fetuses showed significantly increased concentrations of adenosine and there was a positive association with blood oxygen tension. These findings suggest that the fetus responds to tissue hypoxia by increasing blood adenosine concentrations from at least 19 weeks' gestation. PMID- 8439197 TI - Endoscopic balloon dilatation of acquired airway stenosis in newborn infants: a promising treatment. AB - Acquired stenosis of the trachea or bronchus in newborn infants is a possible complication of perinatal intubation and mechanical ventilation. Although the exact pathophysiology is unknown, stenosis formation seems to be initiated by pressure necrosis. Prematurity is thought to be an important risk factor for acquired airway stenosis. Management of stenotic lesions may be conservative, surgical, or endoscopic. Four patients were treated with endoscopic balloon dilatation with satisfactory results. Endoscopic balloon dilatation is the method of choice in most newborn infants with acquired bronchial or tracheal stenosis. PMID- 8439198 TI - Intussusception in preterm infants. AB - Two cases of intussusception in infants born at 26 and 30 weeks' gestation are described. The two infants presented in the neonatal period with abdominal distension, intolerance of feeds, and rectal bleeding. An initial diagnosis of necrotising enterocolitis was made and the infants were treated medically. This led to a delay in the diagnosis of the intussusception. Published work on neonatal intussusception is reviewed and attention is drawn to the fact that the presenting signs and symptoms can be similar to those of necrotising enterocolitis. A diagnosis of intussusception should therefore be considered in any preterm infant with suspected necrotising enterocolitis. PMID- 8439199 TI - Gall bladder contractility in preterm infants. AB - Postnatal response of the gall bladder to feeding was studied in 28 preterm infants (gestational age 24-37 weeks) by ultrasonography immediately before feeding and one hour after feeding. Nineteen of the infants were studied once during the first week of life, and nine infants were studied weekly from a postconceptional age of 27-31 until a postprandial gall bladder contraction was seen. A contraction index was calculated as a percentage decrement of the surface area of the gall bladder from its initial value. All preterm infants of more than 33 weeks' gestation showed a gall bladder response to feeding with a contraction index of at least 50%. Very preterm infants (gestational age 27-32 weeks) showed no postprandial gall bladder contraction or the contraction index was under 50%. In a follow up study of nine very preterm infants, the contraction index exceeded 50% at a postconceptional age of 29 to 32 weeks. One infant with prolonged feeding problems had no postprandial gall bladder response before the postconceptional age of 38 weeks. The contraction index increase was dependent on gestational age at birth and on the bolus volume of feeds. PMID- 8439200 TI - Plasma cholecystokinin concentrations after breast feeding in healthy 4 day old infants. AB - The aim of the present study was to characterise plasma concentrations of cholecystokinin (CCK) after breast feeding in newborn infants. Fifty eight healthy full term exclusively breast fed infants were investigated at 4 (1) (2-6) days of age. Each infant contributed one blood sample collected just before, immediately after, or 10, 30, and 60 minutes after breast feeding. Plasma concentrations of CCK were measured with a technique consisting of high pressure liquid chromatography separation of gastrins and CCKs and consequent analysis with radioimmunoassay. Mean (SD) preprandial plasma concentrations of CCK (CCK8+CCK-33,39) were 68 (17) pmol/l. A significant increase was seen immediately after breast feeding, which was followed by a decline at 10 minutes and a secondary rise was seen at 30 and 60 minutes. The first peak is likely to be due to a suckling related activation of the vagal nerve and the second to a stimulatory effect of food on CCK-producing cells. An inverse relationship between basal concentrations of CCK and age of the infant was found. In rats peripheral injections of CCK reduce food intake and cause postprandial sedation and sleepiness via activation of an afferent vagal mechanism. CCK release in response to breast feeding may therefore in addition to exerting stimulatory effects on digestion and metabolism contribute to relaxation and sleepiness seen after breast feeding. The high CCK concentrations seen in younger infants may help the infant to remain satiated and calm despite receiving very little food during the first days of life. PMID- 8439201 TI - The development of anti-HLA antibodies in multiply transfused preterm infants. AB - The development of antihuman leucocyte antigen antibodies (aHLAA) in response to multiple transfusions in preterm infants was studied prospectively. Fifty seven infants requiring a minimum of two blood transfusions were recruited after obtaining informed written parental consent. They were randomised to receive either whole blood or blood that had been passed through a leucocyte filter. Anti HLAA were sought in maternal and cord blood so as to ensure that any aHLAA detected after transfusion had not been passively transferred antenatally, and in 1 ml samples drawn monthly from the baby, at least 10 days from a previous transfusion, until discharge from hospital. Anti-HLAA were detected by microlymphocytotoxicity assay. Results were obtained in 42 babies, 19 in the filter and 23 in the no filter group. Fifteen babies had to be excluded because of protocol violation or because they died. None of the babies receiving filtered blood developed aHLAA, but seven babies in the no filter group developed aHLAA. In conclusion, multiply transfused preterm infants have the ability to elaborate antibodies to HLA and leucocyte filters may prevent this. PMID- 8439202 TI - Transplacental transfer of cefuroxime in uncomplicated pregnancies and those complicated by hydrops or changes in amniotic fluid volume. AB - The transplacental transfer of cefuroxime was determined at antenatal fetal blood sampling in a cross sectional study of 78 patients between 15-35 weeks' gestation, 8-138 minutes after a maternal intravenous dose of 750 mg. Mean serum cefuroxime concentration, measured by high performance liquid chromatography, was 7.4 (95% confidence interval (CI) 6.8 to 8.1) mg/l in control fetuses; concentrations in hydropic fetuses were similar (6.2 mg/l, CI 4.7 to 7.7) but in fetuses with oligohydramnios they were significantly lower, (4.9 mg/l, CI 3.6 to 6.2). Antibiotic concentration did not correlate with gestational age and remained unchanged by transfusion of packed red cells. We conclude that (i) fetal serum concentrations of cefuroxime obtained after a maternal dose of 750 mg are only adequate for prophylaxis against organisms with a minimum inhibitory concentration of < 4 mg/l and (ii) transplacental passage of cefuroxime is significantly reduced in the presence of oligohydramnios. PMID- 8439203 TI - Diagnosis of patent ductus arteriosus in the preterm newborn. PMID- 8439204 TI - Pulmonary gas exchange immediately after birth in spontaneously breathing infants. AB - The pulmonary gas exchange (rate of oxygen consumption, VO2 and rate of carbon dioxide production, VCO2), heart rate, and transcutaneously measured oxygen saturation were measured during the first five minutes after birth in healthy newborn infants. Fifteen full term infants who were vaginally delivered, 15 full term infants born by caesarean section, and 10 preterm infants born by caesarean section were studied. VO2 tended to be slightly higher than VCO2 during the first minutes, with a gradual change to a respiratory exchange ratio above 1.0. VO2 and VCO2 were significantly higher in vaginally delivered infants than in those born by caesarean section during the second minute after birth, partly due to a higher number of cries/minute. During periods of calm breathing, VO2 and VCO2 were significantly higher in vaginally delivered infants than in those born by caesarean section, with low gas exchange levels in infants born by caesarean section during the second minute after birth. Decreased ventilation was reflected by a significant drop in oxygen saturation within 30-45 seconds. PMID- 8439205 TI - Dr John Ballantyne (1861-1923): perinatologist extraordinary of Edinburgh. PMID- 8439206 TI - Neutrophil chemotaxis and adhesion in preterm babies. PMID- 8439207 TI - Use of sedatives and muscle relaxants in newborn babies receiving mechanical ventilation. PMID- 8439208 TI - Streptococcal toxic shock-like syndrome. The importance of surgical intervention. AB - Pyrogenic exotoxins A, B, and C produced by group A beta-hemolytic streptococci (Streptococcus pyogenes) may cause a syndrome characterized by fever, rash, desquamation, hypotension, and multi-organ-system dysfunction. This syndrome, the streptococcal toxic shock-like syndrome (TSLS), has a rapid and fulminant course closely resembling the staphylococcal toxic shock syndrome (TSS) caused by the staphylococcal toxic shock syndrome toxin-1 (TSST-1). The recent recognition of this syndrome is thought to stem from the appearance of more virulent strains of streptococci that have a greater tendency to produce potent exotoxins than prior strains. During the past 6 years, the authors have treated six patients with TSLS; three of these patients have presented recently. The sites of streptococcal infection associated with the development of the syndrome are frequently in soft tissue and skin. Early diagnosis, treatment with penicillin, and radical operative debridement are required. PMID- 8439209 TI - Efficacy of a beta-lactamase inhibitor combination for serious intraabdominal infections. AB - A double-blind trial was conducted in 385 patients with suspected bacterial intra abdominal infections to compare the efficacy and safety of ampicillin-sulbactam with cefoxitin. Patients were randomized to receive either 3 g ampicillin sulbactam (2 g ampicillin-1 g sulbactam), or 2 g cefoxitin, every 6 hours. To be evaluable, patients had to demonstrate positive culture evidence of peritoneal infection at the time of operation. A total of 197 patients were evaluable for clinical efficacy. The two treatment groups were comparable in demographic features and in the presence of risk factors for infection. Clinical success (absence of infection and of adverse drug reaction) was observed in 86% of patients in the ampicillin-sulbactam group and 78% in the cefoxitin group. Eradication of infection occurred in 88% of the ampicillin-sulbactam group and 79% of the cefoxitin group. There were no differences in the nature or frequency of side effects observed in the two groups. Ampicillin-sulbactam demonstrated no difference in safety or efficacy when compared with cefoxitin in the treatment of serious intra-abdominal infections of bacterial origin. PMID- 8439210 TI - The cost of not wearing seat belts. A comparison of outcome in 3396 patients. AB - Data from the North Carolina Trauma Registry were analyzed to determine the effect of seat belt usage on outcome in motor vehicle accidents. Of 6237 persons involved in motor vehicle accidents, data on seat belt usage were available for 3396. Of these, 1916 were not and 1480 were wearing seat belts. The mean hospital charge in belted patients was $10,500 +/- $18,200; and in unbelted patients, $15,250 +/- $26,300 (p < 0.001). The total hospital charges were $23 million for the 1508 patients not wearing seat belts. If the unbelted patients had outcomes similar to belted patients, the charges resulting from caring for the 1508 patients would have been $15.8 million, a potential savings of $7.2 million. There were 135 deaths among the unbelted patients (7.0%) and 47 deaths among the belted patients (3.2%) (p < 0.001). A similar projection of belted outcome for unbelted patients suggests that seat belt usage could have reduced the unbelted mortality rate by over one half. Patients wearing seat belts also had significantly shorter hospital stays, fewer days in the intensive care unit, and fewer days on the ventilator (p < 0.001). Seat belt usage is associated with a significant decrease in mortality rate, hospital charges, length of stay, intensive care unit stay, and ventilator requirements. Seat belts could have saved at least 74 lives and 7.2 million dollars during the period from October 1, 1987 to July 1, 1989 in patients seen in the seven trauma centers in North Carolina. PMID- 8439211 TI - Indications, technique, and clinical use of ambulatory 24-hour esophageal motility monitoring in a surgical practice. AB - The development of miniaturized electronic pressure transducers and portable digital data recorders with large storage capacity has made ambulatory monitoring of esophageal motor function over an entire circadian cycle possible. The broad clinical application of this new technology in a large number of asymptomatic normal volunteers and patients with primary esophageal motor disorders or gastroesophageal reflux disease provides new insights into esophageal motor function in health and disease under a variety of physiologic conditions. In normal volunteers and symptomatic patients, esophageal motor activity increases with both the state of consciousness and eating activity, i.e., from sleep to awake to meal periods. In the normal situation there is a higher prevalence of nonperistaltic esophageal contractions than appreciated on stationary manometry. Compared with standard manometry, ambulatory esophageal manometry provides a more than 100-fold larger database for the classification and quantitation of abnormal esophageal motor function and leads to a change in the diagnosis in a substantial portion of patients with symptoms suggestive of a primary esophageal motor disorder. In patients with nonobstructive dysphagia, the circadian esophageal motility pattern is characterized by an inability to organize the motor activity into peristaltic contractions during meal periods. In patients with noncardiac chest pain, ambulatory motility monitoring can document a direct correlation of abnormal esophageal motor activity with the symptom and shows that the abnormal motor activity immediately preceding the pain episodes is characterized by an increased frequency of simultaneous, double- and triple-peaked, high-amplitude, and long-duration contractions. A long esophageal myotomy can abolish the ability of the esophagus to produce this abnormal motor pattern. In patients with gastroesophageal reflux disease, ambulatory motility monitoring shows that the contractility of the esophageal body deteriorates with increasing severity of esophageal mucosal injury, compromising the clearance function of the esophageal body. These data suggest that ambulatory esophageal motility monitoring allows for a more precise classification of esophageal motor disorders than standard manometry and can identify abnormal esophageal motor pattern associated with nonobstructive dysphagia, noncardiac chest pain, or gastroesophageal reflux. Ambulatory esophageal manometry therefore should replace standard manometry in the assessment of esophageal body function and has potential to improve the diagnosis and management of patients with esophageal motor abnormalities. The combination of ambulatory 24-hour esophageal manometry with esophageal and gastric pH monitoring is currently the most physiologic way to assess patients with functional foregut disorders. PMID- 8439212 TI - Detection of point mutations in the Kirsten-ras oncogene provides evidence for the multicentricity of pancreatic carcinoma. AB - It has been reported that multicentricity of pancreatic carcinomas extending beyond the pancreatic duct occur in 15% to 40% of patients. This has been difficult to confirm, however, with currently available histologic techniques. Mutations in the Kirsten (Ki)-ras oncogene, which can be detected frequently in pancreatic carcinomas using the polymerase chain reaction (PCR), may serve as a potential clonal marker of the cancer cells. Fifty-three patients with a histopathologic diagnosis of pancreatic carcinoma were selected for the determination of certain Ki-ras mutations through PCR. The authors identified mutations in the Ki-ras codon 12 in 46 of 53 tumors. Two of these 46 tumors had two different mutations to aspartic acid (GAT) and to valine (GTT) in Ki-ras codon 12. Another isolate had an additional mutation in Ki-ras codon 13. The detection of different mutations in the same tumor suggests that there may be multicentricity in pancreatic carcinomas and that its frequency may be as low as 6% of the carcinomas. These results imply that total pancreatectomy for eliminating tumor recurrence due to multicentricity may not be warranted. PMID- 8439213 TI - Water-soluble ethylhydroxyethyl cellulose prevents bacterial translocation induced by major liver resection in the rat. AB - Enteric bacteria might act as pathogens, translocating across the intestinal barrier to extraintestinal sites after major liver resection. In the current study, water-soluble ethylhydroxyethyl cellulose (EHEC) was administered before hepatectomy to evaluate the influence on bacterial translocation induced by major liver resection, phagocytic capacity by visceral and circulating macrophages, enteric bacterial population, and bacterial adherence on the intestinal surface in rats subjected to sham operation or to 70% or 90% hepatectomy. Oral or intravenous (IV) administration of EHEC reduced the incidence of bacterial translocation to mesenteric lymph nodes (MLN) and blood after major liver resection. Oral EHEC appeared more effective than IV administration in protecting against bacterial translocation to MLN in animals with 90% hepatectomy. Ethylhydroxyethyl cellulose (oral and IV) significantly diminished intestinal macrophage uptake capacity of 125I-labeled, heat-killed Escherichia coli as compared with animals without EHEC administration. Overgrowth or colonization of enteric bacteria after major liver resection could be prevented by oral or IV EHEC. Adherence of 14C-labeled, alive E. coli on the intestinal mucosa decreased after EHEC treatment in animals subjected to major liver resection. Systemic arterial pressure and intestinal blood flow markedly decreased from 1 hour and on after 90% hepatectomy. Intravenous administration of EHEC did not improve these alterations. Bacterial hydrophobicity and surface negative charge were significantly reduced 1 hour after bacterial culture with EHEC. Thus, EHEC appears to be a potent agent preventing translocation of enteric bacteria from the gut after major liver resection, by altering the surface characters of enteric bacteria, balancing the enteric microflora, inhibiting bacterial attachment onto the intestinal surface, and blocking phagocytosis by intestinal macrophages. PMID- 8439214 TI - Percutaneous endoscopic gastrostomy. Initial placement by single endoscopic technique and long-term follow-up. AB - Of 598 patients, 595 underwent placement of a percutaneous endoscopic gastrostomy (PEG) tube using a single endoscopy technique and a polyurethane gastrostomy tube. Primary indications were altered mental status and dysphagia. All procedures were performed in the operating room, with 74 patients receiving general anesthesia and 524 intravenous sedatives with or without topical anesthesia. Average operating room time was 34 minutes. Of 208 patients with prior intra-abdominal surgery, 207 underwent successful placement. The overall complication rate was 4.9%, with a major complication rate of 1.3%. One death occurred from presumed leakage at the gastrostomy site with peritonitis. One hundred twenty patients subsequently died of causes unrelated to the gastrostomy tube after 75 +/- 164 days (range, 1 to 972). One hundred fifty-four patients recovered an adequate oral diet and had the PEG removed after 169 +/- 244 days (range, 6 to 1337). The remaining 319 patients continued to use their gastrostomy tube for 1532 +/- 411 days (range, 134 to 2251). The polyurethane gastrostomy tube has been very durable; none has required replacement because of deterioration. PMID- 8439215 TI - A comparison of medium-chain and long-chain triglycerides in surgical patients. AB - Available lipid emulsions made from soybean or safflower oil are classified as long-chain triglycerides (LCT). In contrast, medium-chain triglyceride (MCT) emulsions have different physical properties and are metabolized by other biochemical pathways. To compare the differences between these two fat emulsions, the authors studied 12 surgical patients and 6 volunteers. These subjects were randomly assigned to receive parenteral nutrition with MCT or LCT emulsion. Measurement of arterial and venous concentration differences across the forearm demonstrated that muscle utilization was significantly improved with MCT administration. There was also a trend toward improved nitrogen balance in the MCT group, and less weight loss in the postoperative period also was observed in this group. During the fat clearance test, the serum ketone concentrations were significantly higher in the MCT than the LCT group. The improvement in nitrogen retention may be associated with increasing ketone and insulin levels. Fat emulsions containing 50% MCT are safe for use in parenteral nutrition and may provide an alternate fuel that improves protein metabolism. PMID- 8439216 TI - The effect of postoperative intravenous feeding (TPN) on outcome following major surgery evaluated in a randomized study. AB - Three hundred patients undergoing major general surgical procedures were randomized by means of a computer-assisted algorithm to receive either total parenteral nutrition (TPN) from the first postoperative day or only prolonged glucose administration (250-300 g/day) up to 15 days after operation. All patients receiving TPN were treated individually based on daily measurements of energy and nitrogen balances. The treatment goal was to keep the patients in positive energy balance (+20%) and close to nitrogen balance. The effects of the two "nutrition regimens" on outcome such as mortality rate, complications, the need of additional medical support and patient-related functional disabilities were investigated. No selection of patients was made, that is, malnourished patients were also randomized. There were no differences among TPN versus glucose treatment when results were analyzed according to intent to treat. Approximately 60% of all patients were able to start eating within 8 to 9 days after operation. No differences were observed between such patients regardless of being treated with TPN or glucose only. Patients on glucose treatment during 14 days had a significantly higher mortality rate (p < 0.05) than patients on either continuous and uncomplicated TPN treatment or short-term glucose treatment. Similar results for mortality rates also were seen with regard to severe complications (cardiopulmonary problems, sepsis, and wound-healing insufficiencies), functional disturbances, the need of additional medical support, and abnormalities in nutritional state. Twenty per cent of the patients randomized to TPN treatment showed a statistical trend (p < 0.10) toward a higher mortality rate (36%) compared with patients randomized to prolonged glucose treatment (21% mortality rate). These patients could not be identified by evaluation of preoperative factors. Thus, the overall evaluation of the results makes it likely that a fraction of high-risk patients (approximately 20%) were not doing well on immediate postoperative intravenous feeding, and it is possible that TPN to such patients accentuated their morbidity rate. Although patients (20%) on prolonged semi-starvation (14 days glucose treatment) had increased mortality rate and severe complications, it was possible that undernutrition induced a slightly different complication scenario than induced by TPN in the high-risk patients. The results demonstrate that in most surgical patients (60%), postoperative semi starvation is not a limiting factor for outcome. In remaining 40%, inadequate nutrition was associated with both increased morbidity and mortality rates. In this sense, inadequate nutrition represents both too much and too little, whereas overfeeding seemed to be a larger problem than underfeeding.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8439217 TI - Profile of hyaluronidase activity distinguishes carbon dioxide laser from scalpel wound healing. AB - Hyaluronic acid plays a key role in the process of wound repair. Deposition of this glycosaminoglycan polymer is in turn controlled by levels of the enzyme hyaluronidase. Hyaluronidase activity was examined in a rat incisional skin wound model comparing laser and scalpel wounds. A polyacrylamide gel electrophoresis (PAGE) hyaluronic acid substrate assay was used to detect differences in the rates of appearance, and level, of hyaluronidase activity in wound homogenates. The hyaluronidase activity in laser wounds appeared earlier, had a bimodal distribution, and increased to a higher level than that in scalpel wounds. The origin of hyaluronidase is not clear, but control of its appearance and modulation of its activity may be a more complex process than previously assumed. PMID- 8439218 TI - Talk about not talking. PMID- 8439219 TI - Do physicians have a duty to treat Medicare patients? PMID- 8439220 TI - Offering truth. One ethical approach to the uninformed cancer patient. PMID- 8439221 TI - Recent evidence on drug therapy of mild to moderate hypertension and decreased risk of coronary heart disease. PMID- 8439222 TI - Oral anticoagulant therapy--50 years later. AB - The year 1991 marked the 50th anniversary of the first clinical use of oral anticoagulant therapy as a means of preventing thromboembolic disease. Despite long-term physician familiarity with oral anticoagulants, this mode of therapy still suffers from a relatively high-risk/safety profile. This review briefly highlights important historical and pharmacokinetic points of interest but focuses predominantly on aspects of the day-to-day management of anticoagulant therapy aiming to enhance physician performance in this therapeutic milieu. Emphasis is placed on therapeutic monitoring, understanding the prothrombin time, managing complications, and assessing future innovations for the management of a growing population of patients treated with orally administered anticoagulants. PMID- 8439223 TI - Blood pressure, systolic and diastolic, and cardiovascular risks. US population data. AB - The National High Blood Pressure Education Program (NHBPEP) was launched 20 years ago based on data from population studies and clinical trials that showed high blood pressure (HBP) was a major unsolved--but soluble--mass public health problem. The present review summarizes recent data from US prospective population studies on blood pressure--systolic (SBP), diastolic (DBP)--and cardiovascular risk. The outcome variables include blood pressure-related risks, primarily incidence and mortality from coronary heart disease, stroke, other and all cardiovascular diseases (CVD); also cardiac abnormalities (roentgenographic, electrocardiographic, echocardiographic); also, all-cause mortality and life expectancy. Data accrued during the past 20 years confirm that SBP and DBP have continuous, graded, strong, independent, etiologically significant relationships to the outcome variables. These relationships are documented for young, middle aged, and older men and for middle-aged and older women of varying socioeconomic backgrounds and ethnicity. Among persons aged 35 years or more, most have SBP/DBP above optimal (< 120/< 80 mm Hg); hence, they are at increased CVD risk, ie, the blood pressure problem involves most of the population, not only the substantial minority with clinical HBP. For middle-aged and older persons, SBP relates even more strongly to risk than DBP; at every DBP level, higher SBP results in greater CVD risk and curtailment of life expectancy. A great potential exists for improved health and increased longevity through control of the blood pressure problem. Its realization requires a strategy combining population wide and high risk approaches, the former to prevent rise of blood pressure with age and to achieve primary prevention of HBP by nutritional-hygienic means; the latter to enhance detection, treatment, and control of HBP. The newly expanded goals of the NHBPEP, aimed at implementing this broader strategy for the solution of the blood pressure problem, merit active support from physicians and all health professionals. PMID- 8439224 TI - An analysis of ischemic stroke in an urban southern California population. The University of California, San Diego, Stroke Data Bank. AB - BACKGROUND: Stroke databanks may provide important information regarding regional and temporal variations in the causes of stroke. METHODS: Five hundred consecutive patients presenting to the University of California, San Diego, stroke services with acute ischemic stroke were evaluated prospectively. A specific cause of stroke was assigned in each case according to predetermined diagnostic criteria. RESULTS: Relative incidences of ischemic stroke causes were as follows: lacunar, 27%; unknown cause, 23%; cardioembolic, 22%; large-vessel atherothrombotic/embolic, 18%; and miscellaneous, 10%. CONCLUSIONS: These relatively high rates of lacunar stroke and stroke of unknown cause are similar to those from other recent surveys and may reflect an important shift in the pathophysiologic mechanisms that underlie ischemic stroke. PMID- 8439225 TI - Gender differences in the treatment of patients with acute myocardial infarction. A multihospital, community-based perspective. AB - OBJECTIVE: As part of a community-wide study examining temporal trends in the incidence and survival rates of acute myocardial infarction, we examined differences between the sexes in overall utilization rates and changes over time, therein, of various therapies used in the management of acute myocardial infarction. DESIGN: Nonconcurrent prospective study. PATIENTS: Three thousand three hundred sixty-one men and 2119 women hospitalized with validated acute myocardial infarction in 16 hospitals in the Worcester, Mass, metropolitan area during 1975, 1978, 1981, 1984, 1986, 1988, and 1990. RESULTS: After controlling, by means of a logistic regression analysis, for a variety of patient-related factors that could affect physician prescribing patterns, women were significantly more likely to receive diuretics during hospitalization for acute myocardial infarction, whereas men were significantly more likely to receive antiplatelet agents, lidocaine, and other antiarrhythmic agents. No statistically significant differences were seen between men and women with regard to the use of anticoagulants, beta-blockers, calcium channel blockers, digoxin, nitrates, and thrombolytic agents. Marked increases over time (1975 through 1990) were seen in the use of anticoagulants, antiplatelet agents, beta-blockers, lidocaine, and nitrates in each of the sexes, while declines were seen in the use of digoxin and diuretics. Use of thrombolytic therapy increased between 1986 and 1990, whereas use of calcium channel blockers decreased over this period for both men and women. CONCLUSIONS: The results of this multihospital, population-based, observational study suggest that physician practice patterns in the pharmacologic treatment of men and women hospitalized with acute myocardial infarction are very similar. PMID- 8439226 TI - Anticholinergic drug use and bowel function in nursing home patients. AB - BACKGROUND: We sought to measure the relationship between the use of anticholinergic drugs and bowel dysfunction in nursing home patients. METHODS: The study population consisted of 800 residents (average age, 84.7 years; range, 65 to 105 years) from 12 intermediate-care facilities in Massachusetts. Patient characteristics and actual medication use were documented during a 1-month observation period. Neuropsychological and functional testing was performed on all residents receiving psychoactive medications. Constipation was assessed by measuring the frequency of laxative use. RESULTS: Laxatives were used daily by 74% of residents; 45% received more than one laxative a day. After adjusting for potential confounding by logistic regression modeling, we found that daily laxative use was significantly more common in residents taking highly anticholinergic antidepressants such as amitriptyline (odds ratio, 3.12), diphenhydramine (odds ratio, 2.18), highly anticholinergic neuroleptics such as thioridazine (odds ratio, 2.01), and in the very old (odds ratio, > or = 85 years = 2.23). Gender, decreased functional status, impaired cognitive function, and the use of benzodiazepines or antiparkinsonian agents were not associated with increased use of laxatives. CONCLUSIONS: A strong association exists in institutionalized elderly between the use of specific anticholinergic medications and constipation, as reflected in the increased use of laxatives. This effect was not seen with nonanticholinergic sedatives, nor was it explained by the patients' cognitive or functional status. These drugs may be responsible for substantial iatrogenic effects on bowel function in elderly patients. PMID- 8439227 TI - Chronic Q fever. Ninety-two cases from France, including 27 cases without endocarditis. AB - OBJECTIVE: Chronic Q fever is seldom recognized; before 1989, only 234 cases had been reported in the literature. The 92 cases of chronic Q fever collected at the French National Reference Center for Rickettsioses from 1982 through 1990 represent the largest series ever reported. PATIENTS: The patients included in the study were diagnosed between July 31, 1982, and August 1, 1990, at the French National Reference Center for Rickettsioses as having chronic Q fever by the following criteria: presence of antibody against Coxiella burnetii phase I antigen at a titer greater than or equal to 800 for IgG and 50 for IgA by the indirect immunofluorescence test. Epidemiologic, clinical, laboratory, and treatment data were collected from 39 different collaborative hospitals throughout France. MAIN OUTCOME MEASURE: For each serologically selected patient, a computerized questionnaire was utilized to record 188 different items of demographic, epidemiologic, clinical, laboratory, and therapeutic data, which were analyzed. RESULTS: Chronic Q fever occurs more frequently in city dwellers than in rural inhabitants, and exposure to domestic ruminants and raw milk is an important feature. Immunocompromising conditions (20.2%) and underlying heart disease (88.4%) or vascular disease are the most important risk factors to consider in potential cases of chronic Q fever. The mortality in these patients with endocarditis was high (23.5%). The clinical spectrum of 84 patients included 57 cases of endocarditis, three cases of vascular prosthesis infection, three cases of aneurysmal infection, three cases of osteoarthritis, four cases with lung localizations, nine asymptomatic cases, three cases of hepatitis, and two cases with cutaneous forms of the disease. CONCLUSIONS: In patients with unexplained fever, negative blood cultures, and a history of underlying vascular or cardiac disease, Q fever should be considered. PMID- 8439228 TI - The molar ratio of insulin to C-peptide. An aid to the diagnosis of hypoglycemia due to surreptitious (or inadvertent) insulin administration. AB - After beta-cell stimulation by carbohydrate or other secretagogues, insulin and C peptide are secreted into the portal vein in a 1:1 molar ratio. A large fraction of endogenous insulin is cleared by the liver, whereas C-peptide, which is cleared primarily by the kidney and has a lower metabolic clearance rate than insulin, traverses the liver with essentially no extraction by hepatocytes. Hence, the molar ratio of insulin to C-peptide in peripheral venous blood (ICPR) should be less than 1.0 during fasting and feeding, unless exogenous insulin is introduced into the systemic circulation. Consequently, an ICPR in excess of 1.0 in a hypoglycemic patient argues persuasively for surreptitious or inadvertent insulin administration and against insulinoma (or sulfonylurea ingestion) as the cause of the hypoglycemia. This conclusion is supported by personal experience and by the literature. PMID- 8439229 TI - Acupuncture for reflex sympathetic dystrophy. PMID- 8439230 TI - Fatal right ventricular infarction in association with contraceptive pills, without coronary disease. PMID- 8439231 TI - Expression study with the Escherichia coli lep gene for leader peptidase in phototrophic purple bacteria. AB - Synthesis and assembly of leader peptidase of Escherichia coli (signal peptidase I), was studied by heterologous expression of its lep gene in three species of phototrophic purple bacteria. Cell extracts of the recipient species showed neither cross reaction with antibodies against E. coli leader peptidase nor cleavage of the model substrate M13-procoat in vitro. The lep gene was transferred via conjugation using the plasmid expression vector for phototrophic bacteria pJAJ9. Plasmid-borne leader peptidase enzyme was identified by immunochemical means. However, extracts of transconjugant cells showed no cleavage function. Trypsin digestion studies revealed that the enzyme was not properly integrated across the host membranes. The data suggest that cleaving enzymes for protein export and/or their assembly pathway in purple bacteria differ from the E. coli type. PMID- 8439232 TI - Complete oxidation of benzoate and 4-hydroxybenzoate by a new sulfate-reducing bacterium resembling Desulfoarculus. AB - A new sulfate-reducer "strain SAX" was isolated from an anaerobic marine sediment [Saxild, Denmark]. The isolate was a gram-negative, motile and non-spore-forming rod which sometimes appeared as a curved rod. Strain SAX differed from all described Desulfovibrio-, Desulfobotulus- and Desulfoarculus-species by the ability to degrade aromatic compounds such as benzoate, 4-hydroxybenzoate and phenol completely to CO2. Electron donors used included lactate, pyruvate, malate, fumarate, crotonate and butyrate, while pyruvate was fermented in the absence of an external electron acceptor. Sulfate, thiosulfate or sulfite served as electron acceptors with benzoate as the donor, while nitrate and nitrite did not. The sulfate-reducing bacterium required vitamins and NaCl-concentrations of about 20 g/l. The optimum temperature for growth of strain SAX was 30 degrees C and the optimum pH value was 7.3. The DNA base composition was 62.4 mol% G+C. The strain possessed cytochrome c3, but no desulfoviridin. On the basis of these characteristics and because strain SAX could not be ascribed to any of the existing species therefore assignment as a new species to the genus Desulfoarculus was suggested. PMID- 8439233 TI - Effect of growth temperature on the fatty acid composition of Mycobacterium phlei. AB - In Mycobacterium phlei, fatty acid unsaturation increased with decreasing temperature. The 10-hexadecenoic acid content increased as the temperature was reduced from 35 degrees C to 26-20 degrees C. At lower temperatures tuberculostearic acid decreased while oleic and linoleic acids increased, the latter being found in M. phlei for the first time. Concomitantly palmitic acid content decreased, and the 6- and 9-hexadecenoic acids increased slightly on reducing the temperature from 35 to 10 degrees C. Thus, down to 26-20 degrees C palmitic acid was mainly replaced by 10-hexadecenoic acid. From this range down to 10 degrees C, palmitic and tuberculostearic acids were replaced by oleic and linoleic acids. Consequently, fatty acid branching decreased and mean chain length increased, as the temperature was reduced. These observations support the view that regulation of membrane fatty acid composition is part of microbial temperature adaptation, and that the mechanism behind the responses might be more complex than generally believed. PMID- 8439234 TI - Syntrophic interactions during degradation of 4-aminobenzenesulfonic acid by a two species bacterial culture. AB - During synthrophic growth of Hydrogenophaga palleronii (strain S1) and Agrobacterium radiobacter (strain S2) with 4-aminobenzene sulfonate (4ABS) only strain S1 desaminates 4ABS by regioselective 3,4-dioxygenation. The major part of the metabolite catechol-4-sulfonate (4CS) is excreted and further metabolized by strain S2. Although both organisms harbour activities of protocatechuate pathways assimilation of the structural analog 4CS requires first of all enzyme activities with broader substrate specificity: protocatechuate 3,4-dioxygenase and carboxymuconate cycloisomerase activities were identified which in addition to the natural substrates also convert 4CS and 3-sulfomuconate respectively. 4 Carboxymethyl-4-sulfobut-2-en-4-olide (4SL) was identified as a metabolite. Its further metabolism requires a desulfonating enzyme which eliminates sulfite from (4SL) and generates maleylacetate. Convergence with the 3-oxoadipate pathway is catalyzed by a maleyl acetate reductase, which was identified in cell-free extracts of both organisms S1 and S2. Characteristically, only strain S1 can oxidize sulfite and thus contributes to the interdependence of the two bacteria during growth with 4ABS. PMID- 8439235 TI - Amino acid utilization by the ruminal bacterium Synergistes jonesii strain 78-1. AB - The ruminal bacterium Synergistes jonesii strain 78-1, which is able to degrade the pyridinediol toxin in the plant Leucaena leucocephala, was studied for its ability to utilise amino acids. The organism used arginine, histidine and glycine from a complex mixture of amino acids, and both arginine and histidine supported growth in a semi-defined medium. The products of (U-14C)-arginine metabolism were CO2 acetate, butyrate, citrulline and ornithine. The labelling pattern of end products from (U-14C)-histidine metabolism differed in that carbon also flowed into formate and propionate. Arginine was catabolised by the arginine deiminase pathway which was characterised by the presence of arginine deiminase, ornithine transcarbamylase and carbamate kinase. This is the first report of a rumen bacterium that uses arginine and histidine as major energy yielding substrates. PMID- 8439236 TI - Growth and flagellation of Vibrio fischeri during initiation of the sepiolid squid light organ symbiosis. AB - A pure culture of the luminous bacterium Vibrio fischeri is maintained in the light-emitting organ of the sepiolid squid Euprymna scolopes. When the juvenile squid emerges from its egg it is symbiont-free and, because bioluminescence is part of an anti-predatory behavior, therefore must obtain a bacterial inoculum from the surrounding environment. We document here the kinetics of the process by which newly hatched juvenile squids become infected by symbiosis-competent V. fischeri. When placed in seawater containing as few as 240 colony-forming-units (CFU) per ml, the juvenile became detectably bioluminescent within a few hours. Colonization of the nascent light organ was initiated with as few as 1 to 10 bacteria, which rapidly began to grow at an exponential rate until they reached a population size of approximately 10(5) cells by 12 h after the initial infection. Subsequently, the number of bacteria in the established symbiosis was maintained essentially constant by a combination of both a > 20-fold reduction in bacterial growth rate, and an expulsion of excess bacteria into the surrounding seawater. While V. fischeri cells are normally flagellated and motile, these bacteria did not elaborate these appendages once the symbiosis was established; however, they quickly began to synthesize flagella when they were removed from the light organ environment. Thus, two important biological characteristics, growth rate and flagellation, were modulated during establishment of the association, perhaps as part of a coordinated series of symbiotic responses. PMID- 8439237 TI - Purification of glutaryl-CoA dehydrogenase from Pseudomonas sp., an enzyme involved in the anaerobic degradation of benzoate. AB - Cell-free extracts of Pseudomonas sp. strains KB 740 and K 172 both contained high levels of glutaryl-CoA dehydrogenase when grown anaerobically on benzoate or other aromatic compounds and with nitrate as electron acceptor. These aromatic compounds have in common benzoyl-CoA as the central aromatic intermediate of anaerobic metabolism. The enzymatic activity was almost absent in cells grown aerobically on benzoate regardless whether nitrate was present. Glutaryl-CoA dehydrogenase activity was also detected in cell-free extracts of Rhodopseudomonas, Rhodomicrobium and Rhodocyclus after phototrophic growth on benzoate. Parallel to the induction of glutaryl-CoA dehydrogenase as measured with ferricenium ion as electron acceptor, an about equally high glutaconyl-CoA decarboxylase activity was detected in cell-free extracts. The latter activity was measured with the NAD-dependent assay, as described for the biotin-containing sodium ion pump glutaconyl-CoA decarboxylase from glutamate fermenting bacteria. Glutaryl-CoA dehydrogenase was purified to homogeneity from both Pseudomonas strains. The enzymes catalyse the decarboxylation of glutaconyl-CoA at about the same rate as the oxidative decarboxylation of glutaryl-CoA. The green enzymes are homotetramers (m = 170 kDa) and contain 1 mol FAD per subunit. No inhibition was observed with avidin indicating the absence of biotin. The N-terminal sequences of the enzymes from both strains are similar (65%). PMID- 8439238 TI - Conversion of 2-chloromaleylacetate in Alcaligenes eutrophus JMP134. AB - 2,4-Dichlorophenoxyacetate (2,4-D) in Alcaligenes eutrophus JMP134 (pJP4) is degraded via 2-chloromaleylacetate as an intermediate. The latter compound was found to be reduced by NADH in a maleylacetate reductase catalyzed reaction. Maleylacetate and chloride were formed as products of 2-chloromaleylacetate reduction, the former being funneled into the 3-oxoadipate pathway by a second reductive step. There was no indication for an involvement of a pJP4-encoded enzyme in either the reduction or the dechlorination reaction. PMID- 8439239 TI - Auditory P300 abnormalities and left posterior superior temporal gyrus volume reduction in schizophrenia. AB - Abnormalities in the auditory P300 event-related potential are one of the most robust findings in schizophrenia. To investigate the brain source(s) of this major functional abnormality, we combined P300 recordings with the use of a new generation of magnetic resonance imaging (MRI) technology to examine specific temporal lobe gray matter regions of interest in schizophrenics and normal controls. In schizophrenics, gray matter volume reductions in the left posterior superior temporal gyrus (STG), which includes Heschl's gyrus and the planum temporale, were highly and specifically associated with both P300 amplitude reduction and left < right topographic asymmetry. In contrast, left hippocampus and parahippocampal gyrus gray matter volume reductions, although present in schizophrenics, were not associated with any P300 abnormalities. There were also no statistically significant correlations between P300 amplitude at any of the central or left-sided electrode sites or any of the MRI-defined volumes of gray matter regions of interest in the right temporal lobe, superior frontal gyrus, or cingulate gyrus; additional work will thus be required to determine the role of these regions, if any, in P300 generation, along with the role of other brain areas not examined in the present study. These initial data appear most compatible with a model that postulates a major role for bilateral STG sources in P300 generation: The strongly asymmetric STG volume reduction (left < < right STG volume) found in many schizophrenic subjects produces asymmetric P300 amplitudes (left < < right) at lateral electrode sites, where the influence of the abnormal region is most easily detected. PMID- 8439240 TI - Pseudoautosomal locus for schizophrenia excluded in 12 pedigrees. AB - A pseudoautosomal locus for schizophrenia has been proposed based on observations of an excess of same-sex affected sibling pairs over opposite-sex pairs when the transmitting parent is the father. Such a pattern of partial concordance by sex related to paternal transmission would be difficult to explain by any biologic mechanism other than pseudoautosomal transmission of schizophrenia. To test the pseudoautosomal hypothesis, 37 sibling pairs concordant for the schizophrenia spectrum were identified from 24 nuclear pedigrees. No significant difference in concordance for sex was found between sibships of paternal and maternal transmission of schizophrenia. Next, a linkage analysis was performed in 12 informative pedigrees, examining seven marker loci spanning the pseudoautosomal region. Both strict schizophrenia and a broader schizophrenia spectrum were analyzed as the affected phenotype, and both autosomal dominant and autosomal recessive models were tested. None of the markers supported linkage to either schizophrenia or the schizophrenia spectrum. Lod scores of less than -4 were obtained across the entire pseudoautosomal region by means of multipoint linkage analyses in the autosomal dominant model. In the autosomal recessive model, the respective lod scores were less than -2. We conclude that there is no evidence of a pseudoautosomal locus for schizophrenia in our pedigrees in any of the genetic models we tested. PMID- 8439241 TI - Exclusion of linkage between schizophrenia and the D2 dopamine receptor gene region of chromosome 11q in 112 Irish multiplex families. AB - A leading theory hypothesizes that schizophrenia arises from dysregulation of the dopamine system in certain brain regions. As this dysregulation could arise from abnormal expression of D2 dopamine receptors, the D2 receptor gene (DRD2) on chromosome 11q is a candidate locus for schizophrenia. We tested whether allelic variation at DRD2 and five surrounding loci cosegregated with schizophrenia in 112 small- to moderate-size Irish families containing two or more members affected with schizophrenia or schizoaffective disorder, defined by DSM-III-R. Evidence of linkage was assessed using varying definitions of illness and modes of transmission. Assuming genetic homogeneity, linkage between schizophrenia and large regions of 11q around DRD2 could be strongly excluded. Assuming genetic heterogeneity, variation at the DRD2 locus could be rejected as a major risk factor for schizophrenia in more than 50% of these families for all models tested and in as few as 25% of the families for certain models. The DRD2 linkage in fewer than 25% of these families could not be excluded under any of the models tested. Our results suggest that the major component of genetic susceptibility to schizophrenia is not due to allelic variation at the DRD2 locus or other genes in the surrounding chromosomal region. PMID- 8439242 TI - A linkage study of chromosome 11q in schizophrenia. AB - The long arm of chromosome 11 is of interest in schizophrenia research because of three independent reports of balanced 11q translocations cosegregating with schizophrenia and other major psychiatric illness in pedigrees. In addition, a number of candidate genes for psychosis are located in the translocated regions. These include the dopamine D2 receptor, porphobilinogen deaminase, which has shown an allelic association with schizophrenia, and neural cell adhesion molecule, a cell surface glycoprotein involved in neuronal cell-cell recognition during brain development. To search for a schizophrenia locus on chromosome 11q, we conducted linkage analyses in 12 multiplex pedigrees. Sixteen DNA markers, including the above three candidate genes, were used to screen the entire long arm of chromosome 11. None of these markers were supportive of linkage to schizophrenia regardless of whether the affected phenotype was defined narrowly or broadly, whether high or low penetrance was assumed. Both dominant and recessive models tested more than 130 centimorgans of chromosome 11q, and therefore, the reported translocation regions. The results provide no evidence for a susceptibility locus for schizophrenia on chromosome 11q in these pedigrees. PMID- 8439243 TI - Heritable factors influence sexual orientation in women. AB - Homosexual female probands with monozygotic cotwins, dizygotic cotwins, or adoptive sisters were recruited using homophile publications. Sexual orientation of relatives was assessed either by asking relatives directly, or, when this was impossible, by asking the probands. Of the relatives whose sexual orientation could be confidently rated, 34 (48%) of 71 monozygotic cotwins, six (16%) of 37 dizygotic cotwins, and two (6%) of 35 adoptive sisters were homosexual. Probands also reported 10 (14%) nontwin biologic sisters to be homosexual, although those sisters were not contacted to confirm their orientations. Heritabilities were significant using a wide range of assumptions about both the base rate of homosexuality in the population and ascertainment bias. The likelihood that a monozygotic cotwin would also be homosexual was unrelated to measured characteristics of the proband such as self-reported history of childhood gender nonconformity. Concordant monozygotic twins reported similar levels of childhood gender nonconformity. PMID- 8439244 TI - Advancing a neurodevelopmental origin for schizophrenia. PMID- 8439245 TI - Human sexual orientation. The biologic theories reappraised. AB - Recent studies postulate biologic factors as the primary basis for sexual orientation. However, there is no evidence at present to substantiate a biologic theory, just as there is no compelling evidence to support any singular psychosocial explanation. While all behavior must have an ultimate biologic substrate, the appeal of current biologic explanations for sexual orientation may derive more from dissatisfaction with the present status of psychosocial explanations than from a substantiating body of experimental data. Critical review shows the evidence favoring a biologic theory to be lacking. In an alternative model, temperamental and personality traits interact with the familial and social milieu as the individual's sexuality emerges. Because such traits may be heritable or developmentally influenced by hormones, the model predicts an apparent nonzero heritability for homosexuality without requiring that either genes or hormones directly influence sexual orientation per se. PMID- 8439246 TI - Reply to 'A genetic study of male sexual orientation'. PMID- 8439247 TI - The 25th Walter J. Zeiter Lecture. The greening of physiatry in a golden era of rehabilitation. PMID- 8439248 TI - Long-term use of computerized bicycle ergometry for spinal cord injured subjects. AB - Twenty-eight spinal cord injured subjects who participated in an electrical stimulation bicycle ergometry home program were surveyed to determine perceived benefits, home exercise adherence, and predictors of continued home exercise with electrical stimulation. Subjects were classified as users or nonusers depending upon if they used the electrical stimulation ergometry on a regular basis in the home during the past four months. Nineteen subjects qualified as users and nine were nonusers. Ninety-five percent of the users cycled at least twice per week whereas the majority of the nonusers stopped regular home exercise within one month postclinic discharge. All subjects generally perceived increases in muscle bulk and endurance. Users and nonusers perceived inconsistent results related to spasticity. Minimal effects were noted with neurogenic pain and swelling. Adherence to the home exercise program was significantly related to sex of subject and pre-injury exercise habits. Results are discussed in relation to the costs and benefits of electrical stimulation bicycle ergometry in the home. PMID- 8439249 TI - Motor and sensory recovery following complete tetraplegia. AB - Sixty-one individuals admitted for rehabilitation with a diagnosis of complete tetraplegia due to traumatic spinal cord injury underwent prospective examinations for motor and sensory recovery. The amount of motor, light touch and sharp/dull (pin prick) sensory recovery was independent of the initial neurologic level of injury between C4 and C8. In the interval between one month and one year following injury, the American Spinal Injury Association Motor Score increased an average of 8.6 +/- 4.7. However, the rate of motor recovery rapidly declined in the first six months and then approached plateau. Ninety-seven percent of muscles with Grade 1/5 ("Trace") or 2/5 ("Poor") strength one month after injury recovered to > or = 3/5 ("Fair") strength by the time of first annual follow-up. Muscles with 0/5 strength one month after injury and located one neurological level below the most caudal level having motor function regained > or = 3/5 strength in only 27 percent of cases at one year follow-up and at two levels below in only 1% of cases. PMID- 8439250 TI - Causes of death during the first 12 years after spinal cord injury. AB - A study of 9,135 persons injured between 1973 and 1984 and treated at any of 13 regional spinal cord injury care systems was conducted to compare their age-, sex , race-, and cause-specific mortality rates with those of the general population. All subjects survived at least 24 hours. Follow-up was terminated in December, 1985 when 854 persons (9.3%) had died. Although many persons had multiple causes of death, the leading primary causes were pneumonia, nonischemic heart disease, septicemia, symptoms and ill-defined conditions, pulmonary emboli, and ischemic heart disease. During the study period, spinal cord injured persons were 82.2 times more likely to die of septicemia, 46.9 times more likely to die of pulmonary emboli, and 37.1 times more likely to die of pneumonia than comparable individuals from the general population. Though some cause-specific mortality rates for spinal cord injured persons have declined dramatically, many remain substantially above normal. Before life expectancies increase further, improved methods for preventing and managing these fatal complications must be developed. PMID- 8439251 TI - Depressive symptomatology in persons with spinal cord injury who reside in the community. AB - Depressive symptomatology was studied in a community-based sample of 100 men and 40 women with spinal cord injury. The mean for the Center for Epidemiologic Studies Depression Scale was higher than that reported previously for the general population, and the mean for women was higher than that for men. Findings from the Mobility dimension of the Craig Handicap Assessment and Reporting Technique (CHART) suggested that differences between men and women in degree of mobility within home and community partly mediate the gender difference in depressive symptomatology. Other CHART dimensions, Social Integration and Occupation, were inversely related with depression scores, although these dimensions did not differentiate men and women. A statistically significant relationship was not obtained between depression and disability, assessed by a self-report version of the Functional Independence Measure, or between depression and impairment, reflected by the ASIA Total Motor Index Score. Depression was not related with the presence of either pressure ulcers or presumptive evidence of urinary tract infection. PMID- 8439252 TI - Electromyographic study of overuse syndromes in sign language interpreters. AB - Sign language is the fourth most common language in the United States; this mode of communication involves sustained, repetitive use of the hand, wrist, and arm. Signers, therefore, are at risk of overuse disorders as carpal tunnel syndrome (CTS) and ulnar neuritis (UL). Using electrodiagnostic methods, the prevalence of hand nerve entrapments in signers was investigated. Thirty-three signers, six of whom were deaf, were compared to 21 age-matched controls (mean age = 31 and 29 years; respectively). Demographics were obtained by questionnaire. Physical examination and nerve conduction studies followed; 78 hands were examined. No significant mean differences in median motor or sensory latencies discriminated signers from controls. Although no signer's median SNAP latency was greater than 2 SDs from controls, some signers could be considered "abnormal" by other published criteria (eg, median/ulnar mid-palmer comparisons). Using these, 10 of 33 signers had mild abnormalities, five suggestive of CTS, three of UL, and two of both; of controls, two had CTS and two UL. The ratio of electrodiagnostic abnormalities did not differentiate the two groups (p > .05). Reports of hand and/or wrist pain were extremely high in interpreters (nondeaf signers) and were linked to EMG findings (p < .05). Deaf signers, even those with ED findings consistent with CTS, all reported no symptoms, possibly because their signing is less stressful or learned at an earlier age. PMID- 8439253 TI - Stretchability of the rectus femoris muscle: investigation of validity and intratester reliability of two methods including X-ray analysis of pelvic tilt. AB - Validity and intratester reliability of two test methods designed to identify stretchability of the rectus femoris muscle (RFM) was investigated, combined with x-ray analysis of pelvic tilt in the sagittal plane. The first method is commonly used in clinical practice. The second is a new technique supposed to tilt the pelvis posteriorly and thus further separate the origin and insertion of the muscle. Investigation of validity and intratester reliability of the two methods was made by testing and retesting a random sample of 71 persons. The tests were performed with an equipment that automatically recorded the angle of knee flexion from a previously determined applied torque, indicating the end point of motion for that particular subject. Angle of knee flexion and subjective estimation of pain sensation due to stretch were recorded at each measurement. The pelvic tilt analysis consisted of test-retest reliability of x-ray measurements, comparison between the methods in both starting and final position, and x-ray and electronic goniometer measurements. All applied torques were measured with a strain gauge. Two out of three criteria of validity favored the new method and the third pointed out the two methods as equal. The two methods as well as the x-ray measurements showed high reliability, and the hypothesis of a more posterior tilted pelvis in the new method was confirmed. The electronic goniometer was less sensitive than x-ray, but proposed to analyse pelvic tilt clinically. Methodology procedures for joint angle measurements are discussed. PMID- 8439254 TI - The long-term consequence of strength deficits after menisectomy. AB - This study was undertaken to investigate the long-term effects of a muscular imbalance of the knee extensors of both legs, resulting from a menisectomy and a subsequent training program. Sixteen subjects were tested at the end of an eight week training program and again 28 months later. At the end of the training program strength deficits of 13% (maximum isometric torque) and 28% (maximum isokinetic torque) were found. During the 28-month follow-up a significant increase in the mean isometric torque of the operated leg and the mean isokinetic torque of both legs was observed (p < 0.05). This resulted in a symmetrical maximum isometric and isokinetic torque of the knee extensors of both legs. A physical examination and an interview, which formed part of the 28-month follow up, revealed no indications of knee injury or serious complaints resulting from the strength imbalance present at the end of the training program. It is concluded that the present study does not support the general opinion that a strength imbalance of the knee extensors of both legs will result in further injury to the knee joint. Secondly, it is suggested that the strength of the knee extensors of the operated leg may increase and symmetry may be reached even if the training program is ended and normal activities are resumed. PMID- 8439255 TI - Arm and leg cycle cross-training effect on anaerobic threshold and heart rate in patients with coronary heart disease. AB - It has been suggested that the anaerobic threshold (AT) represents a minimal intensity for eliciting an exercise training adaptation. Thirteen men (age = 66 +/- 9; weight = 81 +/- 13kg) and two women (age = 58 +/- 21; weight = 70 +/- 3kg) with coronary heart disease (CHD) trained for 12 weeks to determine the effect of an exercise regimen composed of three- to six-minute intervals of alternating arm and leg cycling (cross-training) on AT. The patients cross-trained for a total of 30 minutes per session, three days per week. Maximal cycle ergometer tests with breath by breath ventilatory gas analyses were performed before and after training. Peak oxygen uptake increased by 8.9% and peak power output increased (p < .05) by 28.3%, whereas resting heart rate (HR) decreased (p < .05) by 9.6% as a result of the cross-training regimen. Cross-training did not effect a significant change in AT but HR at AT was decreased by 6.3% (p < .05). Arm and leg cross training produced a physiological adaptation and may have reduced the HR threshold for effective exercise training. PMID- 8439256 TI - Standard and four-footed canes: their effect on the standing balance of patients with hemiparesis. AB - We studied 14 patients to test the hypotheses that, when patients with hemiparesis use a cane to assist standing balance, their postural sway decreases and the average position of their center of pressure (COP) shifts forward and towards the cane side, and that there is no difference in either of these parameters between standard and four-footed canes. Each subject stood on a Kistler force platform for three ten-second intervals: one without a cane, one with a standard cane, and one with a four-footed cane. Matched-pairs t tests revealed a significant decrease in both the mediolateral (ML) and anteroposterior (AP) travel (postural sway) when the subjects used the standard cane. There was also a significant shift of the average ML position of the COP toward the cane side when they used a standard cane, but no significant difference in the average AP position. When they used the four-footed cane, neither the differences in travel nor the differences in COP position were significant, although they were similar in magnitude to those measured when they used the standard cane, compared with which there was no significant difference. Two conclusions appear warranted. First, a standard cane has a significant effect on force-platform measures of the standing balance of persons with hemiparesis of mild-to-moderate severity- specifically a reduction in the extent of ML and AP postural sway and a shift in the mean position of the COP toward the cane side. Second, as regards such measures of standing balance, a four-footed cane appears to offer no advantage over a standard one. PMID- 8439257 TI - A computer algorithm for defining the group electromyographic profile from individual gait profiles. AB - A computer algorithm was developed to determine the group electromyographic (EMG) profile for the soleus muscle during free speed level walking. Subjects consisted of 50 adults (21 male, 29 female) with no history of musculoskeletal disease. EMG was recorded from the soleus muscle with wire electrodes, and was normalized by maximum muscle test. Two algorithms (time-adjusted mean profile (TAMP) and mean intensity profile (MIP)) were implemented to construct a group profile from identical individual EMG profiles. In addition, a grand ensemble average (GEAV) of the same individual data was performed. A high positive correlation (omega 2 > .995) was found between MIP and GEAV of EMG data. A control group was established based on mean timing and relative intensity of the individual EMG profiles. The MIP and GEAV were shown to have earlier onsets, later cessations, and extended EMG duration in comparison to control values. No significant differences were observed comparing TAMP and mean values for any measure. PMID- 8439258 TI - Balance evaluation in hemiparetic stroke patients using lateral forces applied to the hip. AB - A technique for assessing balance that involves applying predictable controlled forces to the hips is described. Impairments in hemiparetic stroke patients' balance were documented by comparing their hip movements during and after a push with those of control subjects of similar age. Stroke patients swayed further and took longer to stabilize hip position than did the control subjects. The disturbance to stroke patients' balance caused by the termination of lateral force caused them more difficulty than did the onset of the force. Differences between stroke patients' involved and noninvolved sides were more pronounced on release from a push than at its onset. The implications of the findings for the assessment and treatment of balance after stroke are discussed. PMID- 8439259 TI - Influence of cryotherapy on spasticity at the human ankle. AB - The application of cryotherapy to temporarily reduce spasticity is a widespread clinical practice. A method of quantifying spasticity, based on viscoelastic stiffness measurements at the ankle, was applied to objectively determine the efficacy of cryotherapy in reducing spasticity of the calf. Baseline, cryotherapy and one-hour postcryotherapy measurements of spasticity were performed in 25 subjects with clinical signs of spasticity secondary to traumatic brain injury, spinal cord injury, and stroke. A statistically significant reduction in spasticity occurred during cryotherapy. Postcryotherapy results were equivocal, although there was a tendency for diminished spasticity relative to the baseline measurement. Two subjects showed a clear aggravation of spasticity following cryotherapy, thus leading to the conclusion that dichotomous results are possible. PMID- 8439260 TI - Anaerobic threshold in wheelchair athletes with cerebral palsy: validity and reliability. AB - This study examined the validity and reliability of the anaerobic threshold (AT) using blood lactate (ATLa) and respiratory gas exchange (ATg) criteria during cycle ergometry (CE) and wheelchair ergometry (WE) in athletes with spastic cerebral palsy (CP). Eleven subjects attempted a discontinuous incremental test protocol, two minutes work interspersed with one minute rest, twice each on the CE and WE. Only five out of the 11 subjects were able to complete the CE tests, whereas all the subjects were able to complete the WE test. Inadequate hip flexion due to muscle spasticity was the primary limiting factor during the CE tests. Although the maximal aerobic power using this protocol was reliable during WE (r = 0.89, p < .05), the validity and reliability of the AT identified by two independent evaluators using these two techniques was questionable. Evaluator 1 was able to identify ATLa and ATg in seven out of the 11 cases, whereas evaluator 2 was successful in five and seven cases, respectively. It is unclear from these results whether the poor validity and reliability of the AT was due to the discontinuous test protocol used, or whether it was due to inconsistencies in the rate of lactate diffusion from the muscle into the blood due to variations in muscle spasticity during the test. PMID- 8439261 TI - Steroid psychosis: a cause of confusion on the acute spinal cord injury unit. AB - The use of glucocorticoids has long been known to be associated with a number of side effects. The current use of high-dose methylprednisolone in spinal cord injured patients puts this population at increased risk. In particular, the risk of acute psychotic reactions is increased because it is a dose response relationship. Conservative estimates report an incidence of 5.7%. These reactions place the patient at increased risk of further spinal cord injury and worsening neurologic deficit. We present two cases of possible steroid psychosis in which the mental status changes did indeed place the patients at risk of further injury. PMID- 8439262 TI - Successful treatment of immobilization hypercalcemia using calcitonin and etidronate. AB - Hypercalcemia of immobilization may present in patients with spinal cord injury, multiple fractures, or Landry-Guillain-Barre Syndrome. It is attributed to an increase in bone resorption and diminished bone formation characterized clinically by elevated serum calcium levels, hypercalciuria, increased risk of urinary lithiasis, and renal failure. Traditional treatment methods can interfere with the intensive level of therapy provided in the comprehensive rehabilitation program. Other treatments, less disruptive of the rehabilitation milieu, are possible. Reported are six patients with hypercalcemia of immobilization who were successfully treated with combination therapy of salmon calcitonin and sodium etidronate. The patients developed hypercalcemia an average of 69 days after the onset of illness. Serum calcium levels dropped an average of 2.8mg/dL (12.3mg/dL, SD 1.33 to 9.5mg/dL, SD 0.42) within eight days after initiation of treatment. In two patients, 24 hour urine excretions of calcium decreased by 414 and 210mg/day, respectively. All patients had a reduction in serum calcium levels noted within two days of treatment, and a normal serum calcium levels within one week. Patients were usually changed to a single medication maintenance regimen, sodium etidronate, within a few days. Full therapies in the treatment gyms were given to all patients within a day of initiation of the combined treatment. These two drugs appear to have a rapid and combined effect on the treatment of hypercalcemia of immobilization, and allow full participation in a comprehensive rehabilitation program. PMID- 8439263 TI - Cervical myelopathy presenting as a genu recurvatum gait disorder. AB - A 49-year-old man presenting with a genu recurvatum gait disorder was found to have a cervical myelopathy, probably on the basis of cervical spondylosis and a cervical disc herniation compromising a congenitally narrow cervical spinal canal. Satisfactory resolution of abnormal hyperextension of the knee was achieved through the use of an ankle-foot orthosis. A genu recurvatum gait disorder as the presenting sign of cervical myelopathy does not appear to have been reported previously. PMID- 8439264 TI - Surgical decompression of impingement in the weightbearing shoulder. AB - Shoulder pain is a common affliction, posing particular limitations on the spinal cord injured person. Abnormalities of the rotator cuff mechanism are a common cause of shoulder injury in the general population and it has recently been observed that a large percentage of persons with paraplegia suffer from chronic shoulder pain. This report describes six cases of impingement syndrome in four spinal cord injured persons who depend on upper extremity function for the execution of activities of daily living and mobility. All had failed prolonged trials of conservative therapy and subsequently underwent anterior acromioplasty and when indicated, repair of the supraspinatus tendon. In each case, functional capacity that approached or equalled premorbid levels was achieved. Pain complaints also markedly decreased from preoperative levels. It is suggested that surgical decompression of shoulder impingement and rotator cuff repair may be beneficial in spinal cord injured persons who have failed conservative therapy. Further study is required to determine the long-term efficacy of surgical intervention in this population. PMID- 8439265 TI - Rehabilitation of patients with Hallervorden-Spatz syndrome. AB - Hallervorden-Spatz Syndrome is an infrequently occurring disorder involving pigmentary degeneration of the globus pallidus, red nucleus, and substantia nigra. Resultant corticospinal and extrapyramidal signs and symptoms predominate early in the course of the disease, with concomitant intellectual deterioration paralleling the developing muscular disorder. To date, there have been no reports in the literature of rehabilitative intervention in patients with this disabling pathology. We report the case of a 43-year-old man whose illness spanned 20 years. He was referred for rehabilitation after a precipitous decline in function over the course of six months. An interdisciplinary team approach was implemented and various medical strategies were used, including the initiation of carbidopa levodopa. An improvement in functional skills, communication, and the ability to use cognitive strategies was observed. We conclude that a multidisciplinary team approach and in selected cases, the use of carbidopa-levodopa are valid methods for the rehabilitation of patients with Hallervorden-Spatz Syndrome. PMID- 8439266 TI - Physiatric opportunities through education. PMID- 8439267 TI - Collagen clarification. PMID- 8439268 TI - Coma and vegetative states. PMID- 8439269 TI - In vitro hematological testing of rotary blood pumps: remarks on standardization and data interpretation. AB - Pump test procedures using blood will have to meet several standards not only to obtain reliable results in vitro but also to allow comparison of results of different investigators. This article reviews some of the issues that should be considered in pump testing, especially referring to the discussions held at the International Workshops on Rotary Blood Pumps in 1988 and 1991. The test loop itself should meet some requirements such as constant physiological temperature, standardized circulating volume, control of pressure and flow, and exact definition of the blood-contacting surface. Specifications have to be made concerning the test fluid blood, including sampling technique, anticoagulation, blood gases, pH, and glucose level. Only fresh blood should be used. Heparin is recommended for anticoagulation because it will be used also in vivo. Different procedures for cleaning and rinsing of plastic materials for reuse are mentioned. Bacterial overgrowth, which can lead to extreme oxygen consumption and acidosis, may be avoided through addition of antibiotics (e.g., gentamicin). To be able to compare data of the different working groups, a new modified index of hemolysis (MIH) has been defined. PMID- 8439270 TI - Report on artificial heart work. PMID- 8439271 TI - Tribute to Dr. C. William Hall, founding director of U.S. Artificial Heart Program at NIH (1922-1992) PMID- 8439272 TI - Clinical trials for removal of bilirubin by high-capacity nonionic adsorbent. AB - To remove bilirubin from patients with hyperbilirubinemia, nonionic macroporous adsorbent NK-110 was tailor-made from styrene and divinyl benzene at Nankai University. Five patients were perfused through shunts filled with 500 ml of the above adsorbent. After 2 h of hemoperfusion, total bilirubin decreased within the range of 22-51%. During the treatment, no noticeable changes in electrolytes, urea nitrogen, serum glutamicpyruvic transaminase (SGPT), TTT, and amino acid concentrations were observed. Platelet depletion was satisfactory. Hemoglobin, white cell count, globulin, and albumin showed no remarkable changes. The nonionic adsorbent shows a high efficacy for bilirubin removal and has a great potential for future clinical applications. PMID- 8439273 TI - Open-loop analysis of circulatory system in awake live animals: relations between mixed venous saturation (SvO2) and hemodynamic parameters. AB - In order to derive quantitative relations between the mixed venous hemoglobin saturation (SvO2) and hemodynamic and metabolic parameters in awake live animals, biventricular bypass experiments were conducted in goats using a pair of pneumatic artificial hearts. The artificial hearts were used to bypass continuously the fibrillating ventricles, to control precisely the pump output, and to derive open-loop responses of the peripheral circulatory system. The specially developed reflection-type optical sensors were mounted on each artificial heart to measure continuously arterial and mixed venous SO2 and hemoglobin content ([Hb]), which in combination with pump output data oxygen consumption of the animal was derived on-line for a maximum duration of 40 days. The SvO2 sensitively reflected the changes in respiratory status. [Hb], pump output, and oxygen consumption. The SvO2 was linearly related to the oxygen consumption but showed nonlinear relation to the pump output. The exercise study revealed that the SvO2 level may be used to detect the anaerobic threshold. The SvO2 is a useful parameter to evaluate circulatory status of the patients. PMID- 8439274 TI - Nonpulsatile mode of blood flow required for cardiopulmonary bypass and total body perfusion. AB - Higher morbidity and mortality rates are seen after the use of cardiopulmonary bypass in infants and elderly patients. Clinical procedures acceptable for adult patients may not be acceptable for them. Infants require more effective tissue gas exchange or tissue perfusion because of their active metabolic status. On the other hand, vascular systems of elderly patients are more rigid and do not have enough reserve capacity for nonpulsatile perfusion compared to young adults. More effective tissue perfusion is needed for them during cardiopulmonary bypass. Traditionally, we utilize a nonphysiological, nonpulsatile pump and perfuse the patients with bypass flows below their resting cardiac outputs (70-80%). In our experience, in general, it is necessary to have approximately 20% higher cardiac output in cases where we use a nonpulsatile mode of total body perfusion compared with a pulsatile mode of perfusion. In addition, higher bypass flow is expected to be required for infants because of their higher metabolic rate and for elderly patients because of their more rigid vascular structure. PMID- 8439275 TI - Biology and behavior. A set-point hypothesis of psychological functioning. AB - This article provides a broad overview of an exploratory thesis designed to enhance an understanding of perturbations and rigidities of psychological functioning--a set-point hypothesis of psychological functioning. Historical precedents and parallels with Keesey's set-point theory of obesity are offered. Basic tenets of the hypothesis are detailed, and relevance to clinical behavioral theory is outlined. It is concluded that the set-point hypothesis may provide a framework for conceptualizing clinical cases and optimizing interventions. The thesis appears to be testable; however, the articulation of specific methodologies and research designs must be undertaken before the ultimate usefulness of the set-point hypothesis can be determined. PMID- 8439276 TI - The integration of empirically derived personality assessment data into a behavioral conceptualization and treatment plan. Rationale, guidelines, and caveats. AB - This article suggests that the appropriate integration of personality (trait) data with information gleaned from a traditional behavioral interview will enhance client-treatment matching. The achievement of this goal is predicated on the ability of behaviorists to challenge tightly held (mis)conceptions of the process of "personality" assessment and to apply empirical criteria when engaged in this integrative endeavor. To facilitate such integration, a rationale for the use of dispositionally based assessment data within a behavioral framework is presented. Guidelines are provided for the accurate measurement and integration of such data in addition to a review of caveats that should be considered if such an enterprise is ultimately to reach fruition. PMID- 8439277 TI - Incorporating personality trait measures in behavioral assessment. Nuts in a fruitcake or raisins in a mai tai? AB - Articles by Collins and Thompson, Staats, and Williams and Thompson have taken different tracks, but all advocate the integration of "personality" measures with behavioral assessment. This article addresses several issues that have hindered such integration. First, many traits are poorly defined, inconsistently applied, and excessively molar. The concept of trait communicates a useful idea--that there are meaningful consistencies in behavior across situations. However, the concepts of personality and personality traits are superfluous. They are inbued with semantic imprecision, redundancy, and unwanted psychodynamic and causal connotations. Also, trait measures are insensitive to the dynamic aspects of behavior. Finally, personality assessment questionnaires are frequently used in behavioral assessment but most often for client or subject selection and molar therapy outcome evaluation. The goal of research in this area should be to determine the persons. situations, purposes, particular traits, and measurement methods affecting the utility of trait measures in behavioral assessment. PMID- 8439278 TI - Personality theory, abnormal psychology, and psychological measurement. A psychological behaviorism. AB - Behaviorism, because it has not had a theory of personality, has been separated from the rest of psychology, unable in large part to draw from or contribute to it. Traditional psychology has not had a theory of personality that says what personality is, how it comes about, or how it functions. An antagonism has resulted that weakens rather than complements each tradition. Psychological behaviorism presents a new type of theory of personality. Derived from experimentation, it is constructed from basic theories of emotion, language, and sensory-motor behavior. It says personality is composed of learned basic behavioral repertoires (BBRs) that affect behavior. Personality measurement instruments are analyzed in terms of the BBRs, beginning the behaviorization of this field and calling for much additional research. These multilevel developments are then basic in psychological behaviorism's theory of abnormal behavior and of clinical treatment. The approach opens many new avenues of empirical and theoretical work. PMID- 8439280 TI - L-mandelate dehydrogenase from Rhodotorula graminis: comparisons with the L lactate dehydrogenase (flavocytochrome b2) from Saccharomyces cerevisiae. AB - L-Lactate dehydrogenase (L-LDH) from Saccharomyces cerevisiae and L-mandelate dehydrogenase (L-MDH) from Rhodotorula graminis are both flavocytochromes b2. The kinetic properties of these enzymes have been compared using steady-state kinetic methods. The most striking difference between the two enzymes is found by comparing their substrate specificities. L-LDH and L-MDH have mutually exclusive primary substrates, i.e. the substrate for one enzyme is a potent competitive inhibitor for the other. Molecular-modelling studies on the known three dimensional structure of S. cerevisiae L-LDH suggest that this enzyme is unable to catalyse the oxidation of L-mandelate because productive binding is impeded by steric interference, particularly between the side chain of Leu-230 and the phenyl ring of mandelate. Another major difference between L-LDH and L-MDH lies in the rate-determining step. For S. cerevisiae L-LDH, the major rate-determining step is proton abstraction at C-2 of lactate, as previously shown by the 2H kinetic-isotope effect. However, in R. graminis L-MDH the kinetic-isotope effect seen with DL-[2-2H]mandelate is only 1.1 +/- 0.1, clearly showing that proton abstraction at C-2 of mandelate is not rate-limiting. The fact that the rate determining step is different indicates that the transition states in each of these enzymes must also be different. PMID- 8439281 TI - Effects of chronic 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxy- adenosine (AbeAdo) treatment on polyamine and eIF-5A metabolism in AbeAdo-sensitive and resistant L1210 murine leukaemia cells. AB - We have previously reported that prolonged chronic exposure to the S-adenosyl-L methionine decarboxylase (AdoMetDC) inhibitor, 5'-([(Z)-4-amino-2 butenyl]methylamino)-5'-deoxy-adenosine (MDL 73811, AbeAdo), leads to cytostasis of L1210 cells [Byers, Ganem and Pegg (1992) Biochem. J. 287, 717-724]. Further studies to investigate the mechanism by which these effects are brought about were carried out by comparing an L1210-derived cell line (R20) that is resistant to AbeAdo with the parent cells. The R20 cells were derived by two rounds of AbeAdo-induced cytostasis followed by rescue with exogenous polyamines. Cytostasis was induced in L1210 cells treated for 12 days with 10 microM AbeAdo; however, exposure to up to 40 microM AbeAdo did not induce cytostasis in R20 cells. Putrescine levels were elevated and spermine levels were depleted in both treated L1210 and treated R20 cells. Spermidine was depleted in treated L1210 cells but was only partly reduced in treated R20 cells. AdoMetDC activity was below the limit of detection in treated L1210 cells but, although greatly reduced, could be measured in the treated R20 cells. The resistance of the R20 cells to the effects of AbeAdo on cell growth and spermidine depletion correlated with reduced AbeAdo accumulation by R20 cells. In the absence of spermidine synthesis, unhypusinated eukaryotic translation initiation factor 5A (eIF-5A) accumulated in AbeAdo-treated L1210 cells. There was no detectable accumulation of unhypusinated eIF-5A in R20 cells. Unhypusinated eIF-5A accumulated during AbeAdo treatment was depleted in L1210 cells rescued by exogenous spermidine. These findings are consistent with the hypothesis that AbeAdo-induced cytostasis is due to the loss of hypusinated eIF-5A. However, spermine was able to rescue AbeAdo-treated L1210 cells without significantly reducing the unhypusinated eIF 5A accumulated during AbeAdo treatment, suggesting that only a small amount of the unmodified protein must be hypusinated to restore cell growth. PMID- 8439279 TI - Stress response of yeast. PMID- 8439282 TI - Modulation of expression of endogenous collagenase and collagen genes by electroporation: possible involvement of Ca2+ and protein kinase C. AB - We have investigated the effect of electroporation on the expression of collagen alpha 1(I), collagenase, c-fos and c-jun genes in human dermal fibroblasts (HDF), human smooth muscle cells (HSMC) and HeLa cells. Collagenase and collagen mRNA levels were respectively increased and decreased in a voltage-dependent manner in HDF harvested 2 days after a sham electroporation. These effects were still observed 10 days after electroporation. Similar effects occurred in electroporated HSMC. Neither collagen nor collagenase mRNAs were detected in control or electroporated HeLa cells. c-fos and c-jun mRNA levels were also increased in electroporated HDF, HSMC and HeLa cells harvested 1 h after plating. This suggests that factor AP1 (fos/jun) could mediate the up-regulation of collagenase expression in electroporated HDF and HSMC. When electroporation of HDF was performed in the presence of H7, an inhibitor of protein kinase C, no increase in collagenase mRNA level was observed, suggesting that protein kinase C might be involved in the transduction of the effect. All the effects reported were also suppressed when cells were electroporated in a medium containing EGTA, suggesting that Ca2+ might mediate the transduction of this effect. PMID- 8439283 TI - The pKa of the catalytic histidine residue of chloramphenicol acetyltransferase. AB - A catalytically essential histidine residue (His-195) of chloramphenicol acetyltransferase (CAT) acts as a general base in catalysis, abstracting a proton from the primary hydroxy group of chloramphenicol. The pKa of His-195 has been determined from the pH-dependence of chemical modification. Both methyl 4 nitrobenzenesulphonate and iodoacetamide inactivate CAT by irreversible modification of His-195. The kinetics of inactivation by methyl 4 nitrobenzenesulphonate are pseudo-first-order, and the pH-dependence of inactivation yields a pKa value of 6.60. Iodoacetamide inactivation proceeds with second-order kinetics and a pKa value of 6.80. An alternative site of modification at the active site of CAT is the thiol group of Cys-31, a residue which has no catalytic role. On replacement of Cys-31 with alanine (Ala-31 CAT), the pH-dependence of iodoacetamide inactivation gives a pKa value of 6.66. The pKa values derived from chemical-modification experiments directed at His-195 are in agreement with the pKa values of 6.62 and 6.61 determined for wild-type and Ala-31 CAT respectively from the pH-dependence of kcat/Km. PMID- 8439284 TI - Membrane peptidases on human osteoblast-like cells in culture: hydrolysis of calcitonin and hormonal regulation of endopeptidase-24.11. AB - Five membrane peptidase activities have been identified on cultured human osteoblast-like cells. These consisted of the four exopeptidases aminopeptidase A, aminopeptidase-N, aminopeptidase-W and carboxypeptidase-M, and the endopeptidase, endopeptidase-24.11. The presence of endopeptidase-24.11 was confirmed immunochemically by immunofluorescent staining and by enzyme-linked immunosorbent assay. The inclusion of phosphoramidon partially inhibited the hydrolysis of human calcitonin by a membrane fraction prepared from osteoblast like cell membranes, thus implicating endopeptidase-24.11 in its inactivation. Another metallopeptidase also contributed substantially to calcitonin hydrolysis. Purified porcine endopeptidase-24.11 (1 microgram) was shown to hydrolyse calcitonin with a half-life of 23 min, which compared to a half-life of 0.5 min for substance P under similar conditions. Sequence data revealed that the initial site of hydrolysis of calcitonin was between residues Lys18 and Phe19. The expression of endopeptidase-24.11 by cultured osteoblast-like cells was shown to be modified by various agents: expression was decreased by phorbol 12-myristate 13-acetate (160 nM for 48 h) and increased in the presence of calcitonin (1.5 nM for 48 h) and 1,25-dihydroxyvitamin D3 (0.01-1 microM for 72 h). PMID- 8439285 TI - Oxidation of low-density lipoprotein with hypochlorite causes transformation of the lipoprotein into a high-uptake form for macrophages. AB - Oxidation of low-density lipoprotein (LDL) lipid is thought to represent the initial step in a series of oxidative modification reactions that ultimately transform this lipoprotein into an atherogenic high-uptake form that can cause lipid accumulation in cells. We have studied the effects of hypochlorite, a powerful oxidant released by activated monocytes and neutrophils, on isolated LDL. Exposure of LDL to reagent hypochlorite (NaOCl) at 4 degrees C resulted in immediate and preferential oxidation of amino acid residues of apoprotein B-100, the single protein associated with LDL. Neither lipoprotein lipid nor LDL associated antioxidants, except ubiquinol-10, represented major targets for this oxidant. Even when high concentrations of NaOCl were used, only low levels of lipid hydroperoxides could be detected with the highly sensitive h.p.l.c. post column chemiluminescence detection method. Lysine residues of apoprotein B-100 quantitatively represented the major target, scavenging some 68% of the NaOCl added, with tryptophan and cysteine together accounting for an additional 10% of the oxidant. Concomitant with the loss of LDL's amino groups, chloramines were formed and the anionic surface charge of the lipoprotein particle increased, indicated by a 3-4-fold increase in electrophoretic mobility above that of native LDL on agarose gels. While both these changes could be initially reversed by physiological reductants such as ascorbic acid and methionine, incubation of the NaOCl-modified LDL at 37 degrees C resulted in increasing resistance of the modified lysine residues against reductive reversal. Exposure of mouse peritoneal macrophages to NaOCl-oxidized LDL resulted in increased intracellular concentrations of cholesterol and cholesteryl esters. These findings suggest that lipid-soluble antioxidants associated with LDL do not efficiently protect the lipoprotein against oxidative damage mediated by hypochlorite, and that extensive lipid oxidation is not a necessary requirement for oxidative LDL modification that leads to a high-uptake form of the lipoprotein. PMID- 8439286 TI - Relationship between phosphorylation and translocation to the plasma membrane of p47phox and p67phox and activation of the NADPH oxidase in normal and Ca(2+) depleted human neutrophils. AB - Stimulation of neutrophils with different agonists activates a latent multicomponent NADPH oxidase that reduces molecular oxygen to superoxide anion. Evidence has accumulated that phosphorylation of p47phox (the 47 kDa cytosolic phagocyte oxidase factor) and translocation of the two cytosolic components p47phox and p67phox are essential steps in the activation of NADPH oxidase in response to phorbol esters. We analysed the relationships between activation of the NADPH oxidase and phosphorylation and translocation of p47phox and p67phox in normal and Ca(2+)-depleted neutrophils stimulated by the receptor-mediated agonists formyl-methionyl-leucyl-phenylalanine and concanavalin A. The results produced the following conclusions: (1) Translocation of p47phox and p67phox is an essential mechanism for activation of the NADPH oxidase. (2) A continuous translocation of p47phox and p67phox is necessary to maintain the NADPH oxidase in an activated state. (3) Only a fraction of p47phox and p67phox translocated to the plasma membrane is functional for the activation of the oxidase. (4) Translocation is independent of protein kinase C, and is linked to transmembrane signalling involving Ca2+ transients and production of lipidic second messengers. However, under some conditions, such as in Ca(2+)-depleted neutrophils, translocation can also occur independently of signalling pathways involving production of second messengers from hydrolysis of phospholipids and Ca2+ transients. (5) Phosphorylation of p47phox and p67phox can be quantitatively dissociated from translocation, as staurosporine markedly inhibits phosphorylation but not translocation. (6) The activity of NADPH oxidase is not correlated with the amounts of the phosphorylated proteins present in the plasma membrane. PMID- 8439287 TI - Tumour necrosis factor-induced cytotoxicity is accompanied by intracellular mitogenic signals in ME-180 human cervical carcinoma cells. AB - Tumour necrosis factor-alpha (TNF) induced a cytotoxic response in ME-180 human cervical carcinoma cells in vitro. This cytotoxic response was accompanied by a temporal series of intracellular signals that are commonly triggered by a mitogenic stimulus: increased c-fos (20-30 min) and c-myc (40-60 min) expression, increased activity of ornithine decarboxylase (3 h), increased intracellular polyamine content (7 h) and increased thymidine incorporation into DNA (14 h). A cytotoxic response independent of these mitogenic signals could not be explained by an induction of interleukin-6, which is an autocrine cytotoxic agent in some cell types; nor by a biphasic, dose-dependent response in which low concentrations of TNF are mitogenic and higher concentrations are cytotoxic. Conversely, a dependent role of these mitogenic signals was suggested by the absence of a TNF-promoted increase in thymidine incorporation into DNA in an ME 180 clone that is resistant to TNF-induced cytotoxicity. A decrease in the proliferation rate of TNF-sensitive cells induced by either alpha difluoromethylornithine treatment (resulting in polyamine depletion) or serum starvation rendered the cells insensitive to TNF-induced cytotoxicity, further suggesting a role for mitogenic signals and cell division in TNF-mediated cytotoxicity. However, inhibiting proliferation with cycloheximide resulted in increased sensitivity to TNF, implying that mitogenesis itself was not essential for a cytotoxic response. TNF induced DNA fragmentation in sensitive cells, suggesting that cytotoxicity occurred via apoptosis. PMID- 8439288 TI - Site-directed activation of calpain is promoted by a membrane-associated natural activator protein. AB - Human erythrocytes contain a calpain activator protein with a molecular mass of approx. 40 kDa. The activator is present in association with the plasma membrane and promotes expression of calpain activity at a concentration of Ca2+ close to physiological values. The initial step of the activating mechanism involves association of the activator with calpain, followed by autoproteolytic activation of the proteinase in the presence of 1 microM Ca2+, at a rate identical to that induced by 1 mM Ca2+. In a reconstituted system, the activator binds to erythrocyte membranes, but not to phospholipid vesicles, suggesting the participation of an intrinsic membrane protein(s). In its membrane-associated form the activator selectively binds calpain, thus favouring interaction of the proteinase with the inner surface of plasma membranes. These results further confirm the importance of a natural activator protein in promoting intracellular activation of calpain under physiological conditions through a site-directed mechanism, which explains the high specificity of the proteinase for membrane of cytoskeletal proteins. PMID- 8439289 TI - The characterization of glutathione S-transferases from rat olfactory epithelium. AB - The glutathione S-transferases (GSTs) of rat olfactory epithelium have been characterized with regard to substrate specificity and subunit composition and compared to those of the liver. The presence of cytosolic GST activity in rat olfactory epithelium was confirmed and, using 1-chloro-2,4-dinitrobenzene as substrate, was found to be approximately one-third that of the liver. Olfactory microsomal GST activity was greater than that of liver microsomes and could be activated by treatment with the sulphydryl agent N-ethylmaleimide. The subunit and isoenzyme profile of GSTs in the olfactory epithelium was investigated using a number of techniques. (1) Olfactory GSTs were characterized using a range of relatively subunit-specific substrates. Activities ranged from 40-90% of those found in liver. Most noticeable was the extremely low olfactory activity with the substrate specific for subunit 1. (2) Immunoblotting with antibodies against specific rat hepatic GSTs confirmed the presence of a number of subunits and the absence of subunit 1. (3) F.p.l.c. chromatofocusing and reverse-phase h.p.l.c. indicated that the cytosolic GST profile of olfactory epithelium is unique and is made up of subunits 2, 3, 4, 7, 8 and 11 with subunits 3 and 4 predominating. There is an absence of isoenzymes containing subunit 1. PMID- 8439290 TI - Evolutionary families of peptidases. AB - The available amino acid sequences of peptidases have been examined, and the enzymes have been allocated to evolutionary families. Some of the families can be grouped together in 'clans' that show signs of distant relationship, but nevertheless, it appears that there may be as many as 60 evolutionary lines of peptidases with separate origins. Some of these contain members with quite diverse peptidase activities, and yet there are some striking examples of convergence. We suggest that the classification by families could be used as an extension of the current classification by catalytic type. PMID- 8439291 TI - Disruption of the processing alpha-mannosidase gene does not prevent outer chain synthesis in Saccharomyces cerevisiae. AB - Processing of N-linked oligosaccharides in Saccharomyces cerevisiae begins with the removal of glucose and mannose residues from Glc3Man9GlcNAc2 to form a single isomer of Man8GlcNAc2. The importance of mannose removal for subsequent outer chain synthesis was examined in strains of S. cerevisiae disrupted in the MNS1 gene encoding a specific alpha 1,2-mannosidase responsible for Man8GlcNAc2 synthesis [Camirand, Heysen, Grondin and Herscovics (1991) J. Biol. Chem. 266, 15120-15127]. Both MNS1 transcripts of 1.85 kb and 1.7 kb were not observed in Northern blots of mns1 cells (i.e. cells containing the disrupted gene). Analysis on Bio-Gel P-6 of endo-beta-N-acetylglucosaminidase-H-sensitive oligosaccharides following a 10 min pulse with [2-3H]mannose revealed similar amounts of labelled outer chains excluded from the gel in both control and mns1 cells. H.p.l.c. of the included oligosaccharides showed that a Man9GlcNAc, rather than a Man8GlcNAc, intermediate was formed in mns1 cells. Analysis of [3H]mannose-labelled core oligosaccharides from immunoprecipitated CPY and invertase by h.p.l.c. showed a similar size distribution in mns1 and control cells. Invertase immunoprecipitated from [35S]methionine-labelled mns1 cells was highly glycosylated, but migrated slightly faster than that from control cells on denaturing PAGE, indicating a small difference in glycosylation. A similar difference in mobility was observed for invertase activity stain following non-denaturing gel electrophoresis. It is concluded that the alpha-mannosidase encoded by MNS1 is the only enzyme responsible for mannose removal in vivo, and that this processing step is not essential for outer chain synthesis. PMID- 8439292 TI - Folate transport in intestinal brush border membrane: involvement of essential histidine residue(s). AB - We examined the possible existence of histidine residue(s) in the folate transporter of rabbit intestine. This was done with use of the histidine-specific reagent diethyl pyrocarbonate (DEPC) and purified intestinal brush-border membrane vesicles. DEPC caused significant concentration- and time-dependent inhibition of folic acid transport. The inhibition was only seen when transport was examined in vesicles incubated in buffer at pH 5.2 and not in those incubated in buffer at pH 7.4. The addition of unlabelled folic acid to vesicle suspension before treatment with DEPC (2.5 mM) led to a significant (P < 0.01) protection (84%) against the inhibition of folic acid transport. Treating vesicles pretreated with DEPC (2.5 mM) with reducing reagents (dithiothreitol, 2 mercaptoethanol and 2,3-dimercaptopropanol, all at a final concentration of 10 mM) did not reverse the inhibitory effect of DEPC on folic acid transport. On the other hand, treating the DEPC-pretreated vesicles with hydroxylamine (140 mM) led to a significant reversal (P < 0.01) (54%) of the inhibition of folic acid transport. The inhibitory effect of DEPC on carrier-mediated folic acid transport was found to be mediated through a decrease in the Vmax. (i.e. a decrease in the number and/or activity) of the carriers and an increase in the apparent Km (i.e. a decrease in their affinity), classifying the effect as a mixed-type inhibition. These results demonstrate the existence of critical histidine residue(s) in the intestinal brush-border-membrane folate transporter which is essential for its interaction with, and transport of, the vitamin. These findings also suggest that the histidine residue(s) is located at (or near) the substrate-binding site. PMID- 8439293 TI - Characterization of the inhibition by stilbene disulphonates and phloretin of lactate and pyruvate transport into rat and guinea-pig cardiac myocytes suggests the presence of two kinetically distinct carriers in heart cells. AB - 1. The kinetics of transport of pyruvate (Km 0.20 mM), L-lactate (Km 2.2 mM) and D-lactate (Ki 10.2 mM) into rat cardiac myocytes were studied and compared with those for guinea-pig heart cells [Poole, Halestrap, Price and Levi (1989) Biochem. J. 264, 409-418] whose equivalent values were 0.07, 2.3 and 6.6 mM respectively. Maximal rates of transport were about 5-fold higher in the rat heart cells. 2. 4,4'-Dibenzamidostilbene-2,2'-disulphonate (DBDS), a powerful inhibitor of monocarboxylate transport into erythrocytes [Poole & Halestrap (1991) Biochem. J. 275, 307-312], was found to be a potent but apparently partial inhibitor of lactate and pyruvate transport, with an apparent Ki value at 0.5 mM L-lactate of about 16 microM in both species. Maximal inhibition was 50% and 80% in rat and guinea-pig cells respectively. 3. The maximal extent of inhibition and apparent Ki values were dependent on both the substrate transported and its concentration. Maximum inhibition was less and the Ki was greater at higher substrate concentrations. 4. A variety of other stilbene disulphonates were studied which showed different Ki values and maximal extents of inhibition. 5. Phloretin was a significantly less potent inhibitor of transport into both rat (Ki 25 microM) and guinea-pig (Ki 16 microM) heart cells than into rat erythrocytes (Ki 1.4 microM). In the rat but not the guinea-pig heart cells, inhibition appeared partial (maximal inhibition 84%). 6. We demonstrate that our results can be explained by the presence of two monocarboxylate carriers in heart cells, both with Km values for L-lactate of about 2 mM and inhibited by alpha cyano-4-hydroxycinnamate, but with different affinities for other substrates and inhibitors. One carrier is sensitive to inhibition by stilbene disulphonates and has lower Km values for pyruvate (0.05-0.10 mM) and D-lactate (5 mM), whereas the other has higher Km values for pyruvate (0.30 mM) and D-lactate (25 mM), and is relatively insensitive to stilbene disulphonates. Rat heart cells possess more of the latter carrier and guinea-pig heart cells more of the former. 7. The significance of these results for the study of lactate transport in the perfused heart is discussed. PMID- 8439294 TI - Purification and characterization of a DNA-binding heterodimer of 52 and 100 kDa from HeLa cells. AB - In studies of protein binding to the upstream region of the human proliferation associated antigen p120 gene, a heterodimer of 52 and 100 kDa proteins was purified from HeLa cells. A 1:1 ratio of p52 and p100 was constant throughout the purification. The heterodimer was localized to cell nuclei, as shown by immunofluorescence. The pI values of the p52 and p100 were 7.8 and 8.6 respectively. The peptide sequences obtained for p52 (QSNKTFNLEKQNHTPRKKHQ and PLRGKQLRVRFAAHSASLTVR) and for p100 (PGGPKPGGGPGLSTPGGHPKPPHRGGGEPPRGRQ and GPGPGQSGPKPPIPPPPPHQQ) were not found in the computer databanks. One p52 peptide sequence, PLRGKQLRVRFA, shows considerable sequence similarity to a conserved motif in topoisomerase II of multiple species. The p52/100 heterodimer bound to different DNA probes. The binding was competed by poly(dI-dC), sonicated salmon sperm DNA, and circular or linearized plasmid DNA. The optimal DNA binding for the heterodimer was at pH 7-9 with low salt. The DNA-binding subunit of the heterodimer was the p100 polypeptide, as shown by u.v.-cross-linking assays and Southwestern blots. PMID- 8439295 TI - Temperature-induced membrane-lipid adaptation in Acanthamoeba castellanii. AB - A method has been developed for the separation of the major membrane fractions of Acanthamoeba castellanii after growth at different temperatures. The acyl-lipid compositions of individual membrane fractions, microsomal membranes, plasma membrane and mitochondria were analysed after a shift in culture temperature from 30 degrees C to 15 degrees C. The major change in lipid composition observed was an alteration in the relative proportions of oleate and linoleate. This reciprocal change was seen in all the membrane fractions, but occurred most rapidly in the phosphatidylcholine of the microsomal fraction. Thus, there appears to be a rapid induction of delta 12-desaturase activity in A. castellanii after a downward shift in growth temperature. Changes were also seen in the proportions of the n-6 C20 fatty acids, with a decrease in the proportions of icosadienoate and increases of icosatrienoate and arachidonate. However, unlike the alteration in oleate/linoleate ratios, this change was not seen in all the individual lipids of each membrane fraction. PMID- 8439296 TI - Purification and characterization of 5-aminolaevulinic acid dehydratase from Escherichia coli and a study of the reactive thiols at the metal-binding domain. AB - 5-Aminolaevulinic acid dehydratase (ALAD) from a recombinant strain of Escherichia coli was purified to homogeneity. The enzyme is a homo-octamer of subunit M(r) 36554 +/- 17. Enzyme activity was dependent on the presence of Zn2+ ions and an exogenous thiol. Two molar equivalents of Zn2+ are bound/mol of subunit under reducing conditions. On exposure to the metal chelator EDTA, the two Zn2+ ions are removed, giving an inactive metal-depleted apo-ALAD. On oxidation of holo-ALAD, two disulphide bonds are formed with the loss of 1 mol of Zn2+/mol of subunit. The formation of the first disulphide led to the loss of catalytic activity. Replacement of the two bound Zn2+ ions with Co2+ resulted in the formation of a green protein with a spectrum indicative of the presence of charge-transfer bands from one or more cysteine-Co2+ ligands. While Mg2+ could not activate apo-ALAD alone, it was able to substitute for the second molar equivalent of bound Zn2+, leading to a further 4-fold stimulation in activity. The four cysteine residues involved in the formation of the two disulphide bonds were identified by protein-chemistry studies and were all located in a region of the protein extending from amino acid residues 120-134. Protein sequence data obtained in the present study has permitted the resolution of several differences between the published gene-derived protein sequences for ALAD from E. coli. PMID- 8439297 TI - Ionization characteristics of the Cys-25/His-159 interactive system and of the modulatory group of papain: resolution of ambiguity by electronic perturbation of the quasi-2-mercaptopyridine leaving group in a new pyrimidyl disulphide reactivity probe. AB - 1. A new thiol-specific reactivity probe 4,4'-dipyrimidyl disulphide [compound (VII), m.p. 110 degrees C, pKa of its monohydronated form 0.91] was synthesized and used to resolve the ambiguity of interpretation of the behaviour of papain (EC 3.4.22.2) in alkaline media known to depend to varying extents on two ionizations with pKa values approx. 8.0-8.5 and > or = 9.5 respectively. 2. A new extensive pH-second-order rate constant (k) data set for the reaction of papain with 2-(acetamido)-ethyl 2'-pyridyl disulphide (IV) demonstrated the existence of a striking rate maximum at pH approx. 4, the independence of k around pH 8 and the increase in k with increase in pH across a pKa value of 10.0, behaviour similar to that of other 2-pyridyl disulphides (R-S-S-2-Py) that lack key substrate-like binding sites in R. 3. Although the simplest interpretation of the pKa value of 10.0 assigns it to the formation of (Cys-25)-S-/(His-159)-Im from the ion-pair state of the papain catalytic site, another interpretation may be conceived in which this pKa value is assigned to another group remote from the catalytic site, the state of ionization of which modulates catalytic-site behaviour. This alternative assignment is shown to require compensating effects in the pH region around 8 such that the formation of (Cys-25)-S-/(His-159)-Im across pKa 8.0-8.5 is without net kinetic effect in the reactions of simple 2 pyridyl disulphides such as compound (IV) and 2,2'-dipyridyl disulphide (II). 4. The lower basicity of compound (VII) relative to that of compound (II) (pKa 2.45) was predicted to diminish or abolish the compensation postulated as a possibility in reactions of 2-pyridyl disulphides because of the decreased effectiveness of reaction via a (His-159)-Im+H-assisted transition state. The characteristics of the pH-dependence of the reaction of papain with compound (VII) which are quite different from those for its reaction with compound (II) support both this prediction and the alternative assignment with a value of 8.3 for the pKa of the formation of (Cys-25)-S-/(His-159)-Im. 5. Evidence that the behaviour of papain towards both substrates and some substrate-derived time-dependent inhibitors is determined not only by the loss of the (Cys-25)-S-/(His-159)-Im+H ion-pair state by dehydronation with pKa 8.3 but also by another ionization of pKa approx. 10.0 is briefly discussed. PMID- 8439298 TI - Studies on the inhibitory mechanism of iodonium compounds with special reference to neutrophil NADPH oxidase. AB - Diphenyleneiodonium (DPI) and its analogues have been previously shown to react via a radical mechanism whereby an electron is abstracted from a nucleophile to form a radical, which then adds back to the nucleophile to form covalent adducts [Banks (1966) Chem. Rev. 66, 243-266]. We propose that the inhibition of neutrophil NADPH oxidase by DPI occurs via a similar mechanism. A reduced redox centre in the oxidase could serve as electron donor to DPI, and inhibition would occur after direct phenylation of the redox cofactor, or of adjacent amino acid groups by the DPI radical. In the absence of an activatory stimulus, human neutrophil NADPH-oxidase was not inhibited by DPI. The Ki for time-dependent inhibition by DPI of human neutrophil membrane NADPH oxidase was found to be 5.6 microM. Inhibitory potency of DPI was shown to be directly related to rate of enzyme turnover, indicating the need for a reduced redox centre. Adducts were formed between photoreduced flavin (FAD or FMN) and inhibitor (DPI or diphenyliodonium). These were separated by h.p.l.c. and characterized by absorbance spectroscopy, 1H-n.m.r. and fast-atom-bombardment m.s. and found to have properties consistent with substituted 4a,5-dihydroflavins. After incubation of pig neutrophil membranes with DPI, the quantity of recoverable intact flavin was greatly diminished when NADPH was present to initiate oxidase turnover, indicating that the flavin may be the site of DPI activation. These results may provide a common mechanism of action for iodonium compounds as inhibitors of other flavoenzymes. PMID- 8439299 TI - Mechanisms of hepatic phosphatidylcholine synthesis in the developing guinea pig: contributions of acyl remodelling and of N-methylation of phosphatidylethanolamine. AB - Hepatic phosphatidylcholine (PC) from the immature fetal guinea pig at day 55 of gestation comprised mainly unsaturated molecular species containing C18:2(n-6) and C22:6(n-3) at the sn-2 position, reflecting placental permeability to essential fatty acids. At both day 55 and term (day 68), [Me-14C]choline was incorporated in utero over 3 h largely into sn-1-C16:0 PC species, with incorporation into sn-1-C18:0 PC species increasing by 18 h of incubation. Comparison of specific radioactivities after 3 h and 18 h suggests PC acyl remodelling by phospholipase A1. No incorporation into C20:4(n-6)-containing PC species could be detected of either [Me-14C]choline in vivo or CDP-[Me 14C]choline in isolated microsomes. The major phosphatidylethanolamine (PE) species were 16:0/22:6 and 18:0/22:6. Although [14C]ethanolamine was initially incorporated mainly into sn-1-C16:0 species, specific-radioactivity analysis suggested differential turnover rather than acyl remodelling. [1,2 14C]Ethanolamine and [Me-14C]methionine incorporation into PC molecular species indicated that both newly synthesized and total PE pools were available for N methylation. Since the PC pool synthesized from PE included C20:4- and C22:6 containing species, N-methylation may provide a mechanism for supplying essential long-chain fatty acids to developing tissues that can be regulated independently from bulk PC synthesis. PMID- 8439300 TI - Catalytic-site characteristics of the porcine calpain II 80 kDa/18 kDa heterodimer revealed by selective reaction of its essential thiol group with two hydronic-state time-dependent inhibitors: evidence for a catalytic site Cys/His interactive system and an ionizing modulatory group. AB - 1. Four calpain II heterodimers (80 kDa/30 kDa, 80 kDa/29 kDa, 80 kDa/26 kDa and 80 kDa/18 kDa) were isolated from fresh porcine kidney by (NH4)2SO4 precipitation, chromatography on DEAE-Sepharose CL-6B and subsequently on Reactive Red 120/agarose followed by f.p.l.c. on a Q-Sepharose Hi-Load 16/10 column. 2. The major component (80 kDa/30 kDa) was used to provide the catalytically active calpain II 80 kDa/18 kDa heterodimer by treatment with CaCl2; titration with trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane (E64) in the presence of monothioglycerol showed the preparation to have 1.0 +/- 0.05 catalytic sites per molecule of heterodimer. 3. The 80 kDa/30 kDa heterodimer was separated from monothioglycerol and other low-molecular-mass material by gel filtration on Sephadex G-25 without loss of catalytic activity towards sulphanilic acid/azocasein in the presence of added Ca2+. On storage overnight at a concentration of 3 microM in KCl at 4 degrees C in the absence of Ca2+ the activator-free preparation still produced fully active 80 kDa/18 kDa heterodimer on addition of Ca2+. 4. Activator-free 80 kDa/30 kDa heterodimer (in the absence of Ca2+) reacts relatively slowly with ethyl 2-pyridyl disulphide at pH 5.9; over 5000 s five thiol groups per molecule react, all at similar rates. In the presence of 8 mM CaCl2 under otherwise identical conditions (and also in the pH range 3.8-10.4) an initial faster phase of reaction corresponding to approx. one thiol group per molecule of heterodimer is generated, but it is not cleanly separated from the subsequent slower reactions on the stopped-flow trace. This fast phase of reaction does not occur when E64-inactivated calpain II is substituted for active 80 kDa/18 kDa heterodimer. 5. Greatly improved resolution of the fast phase of reaction involving the catalytic-site thiol group was achieved by using 2,2'-dipyridyl disulphide (2-Py-S-S-2-Py) instead of ethyl 2 pyridyl disulphide. 6. The pH-dependence of the second-order rate constant (k) for the reaction of the catalytically active activator-free 80 kDa/18 kDa calpain II heterodimer with 2-Py-S-S-2-Py was studied by stopped-flow spectral analysis in the pH range approx. 3-8 without interference from reactions of other thiol groups. 7. The form of the pH-k profile establishes for the first time the existence of an interactive catalytic site system [probably containing a (Cys)-S /(His)-Im+H ion pair] analogous to those present in monomeric non-Ca(2+) activated cysteine proteinases.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8439301 TI - Factors which affect the activity of purified rat liver acyl-CoA oxidase. AB - The activity of the enzyme acyl-CoA oxidase (EC 1.3.99.3) is influenced by detergents. At concentrations above the critical micellar concentration, Triton X 100, Triton X-114 and Thesit stimulate oxidase activity. Lower concentrations of Triton X-100 and Triton X-114 render the acyl-CoA oxidase less sensitive towards substrate inhibition by palmitoyl-CoA or dec-4-cis-enoyl-CoA. Other detergents inhibited the enzyme activity. CoA was found to be a relatively powerful competitive inhibitor of the enzyme, with a Ki,slope value of 63 +/- 3 microM. This inhibition is dependent on an intact CoA molecule, as dephospho-CoA, dethio CoA and acetyl-CoA are less potent inhibitors of the enzyme. Dec-2-trans-enoyl CoA is a product-inhibitor of acyl-CoA oxidase, with a Ki,slope value of 7 +/- 1 microM. PMID- 8439302 TI - Differential expression of corticostatins/defensins: higher levels of CS-4 (NP-2) transcripts compared with CS-6 (NP-5) in rabbit lung. AB - cDNA clones encoding two members of the corticostatin (CS)/defensin family of peptides have been isolated from a rabbit bone marrow cDNA library through cross hybridization with cDNA encoding the human corticostatin HP-4. They encode the precursors of CS-4 (NP-2, MCP-2) and CS-6 (NP-5). Highly specific probes were generated for Northern blotting of RNA from various normal rabbit tissues. Both detected high levels of message in bone marrow, moderate in spleen, and low in thymus. In lung, however, while moderate levels were detected with the CS-4 probe, CS-6 message was barely detectable. This correlates with the report of CS 4, but not CS-6 peptide in lung macrophages, and implies that differential regulation of CS/defensin expression in rabbit lung is at the level of gene transcript abundance. PMID- 8439303 TI - Interaction of actin with positively charged phospholipids: a monolayer study. AB - The interactions of actin, a negatively charged cytoskeletal protein, with lipids have been studied by the monolayer technique. The lipids (either pure phosphatidylcholine or incorporating 10%, 30% or 50% of a positively charged surfactant, stearylamine) were spread at the air/water interface and actin was allowed to interact with the monolayer after injection in the subphase. The results show that at a given surface pressure, increasing the density of positive charges in the lipid monolayer causes a significant increase in the intercalation of the actin within the lipid molecules, thereby indicating that the adsorption of actin is facilitated by electrostatic interactions. However, this intercalation is only possible up to a critical surface pressure above which actin does not penetrate the lipid surface. PMID- 8439304 TI - Biosynthesis and secretion of growth factor proteins by kidney cells from DES treated Syrian hamsters. AB - Long-term estrogen treatment of Syrian hamsters results in the initiation and development of hormone-dependent renal adenocarcinomas. The pathway(s) to neoplastic transformation remain unknown in this animal model of hormonal carcinogenesis. In the present study, short-term primary kidney cell cultures and incubations of freshly prepared kidney slices have been incubated with [35S] methionine to study the effects of estrogen treatment on protein biosynthesis in the Syrian hamster. An increase in amount of two secreted proteins were observed with an increasing duration of diethylstilbestrol (DES) treatment. Further characterization of these proteins by two-dimensional electrophoresis identified two proteins present only in treated hamsters, a 20-22 kDa protein and a 16-18 kDa protein with an isoelectric point of 8.5-9.0. Immunoprecipitation using specific antibodies to growth factors, followed by separation on SDS-PAGE electrophoresis, showed that kidney slices from five month-treated animals produced a TGF-alpha-like protein and a bFGF-like protein. The induction of these growth factors may play an important role in the tumorigenic process in kidneys of Syrian hamsters, including cell proliferation and vascularization of the tumor tissue. PMID- 8439305 TI - Anti-Candida activity of cispentacin: the active transport by amino acid permeases and possible mechanisms of action. AB - Cispentacin tranport into Candida albicans CCH442 was via a specific inducible proline permease and other amino acid permeases. Drug entry was also dependent upon the proton motive force. The apparent Km and Vmax for drug uptake under induced conditions were 0.4 mM and 7 nmol/microliter/min, respectively, with cellular accumulation in the mM range. Cispentacin uptake was competitively inhibited by L-proline with an apparent Ki of 75 microM. Cispentacin did not charge to transfer-RNA or incorporate into protein; however, the compound did inhibit in vivo incorporation of [14C]lysine into protein and [3H]adenine into RNA as well as in vitro [14C]proline charging to transfer-RNA. Cispentacin did not inhibit amino acid biosynthesis in vivo but did elevate levels of several amino acids possibly by interfering with self-regulatory mechanisms. PMID- 8439306 TI - pH-dependent decarboxylation of 2-amino-3-ketobutyrate, the unstable intermediate in the threonine dehydrogenase-initiated pathway for threonine utilization. AB - 2-Amino-3-ketobutyrate can be readily formed enzymatically by the action of L threonine dehydrogenase. A convenient assay for determining the half-life of this beta-keto acid is afforded by its rapid and quantitative conversion to glycine (+ acetyl CoA), as catalyzed by 2-amino-3-ketobutyrate CoA lyase. Using this system, we have found the half-life of 2-amino-3-ketobutyrate varies with pH from 8.6 minutes at pH 5.9 to 140 minutes at pH 11.1 yielding a theoretical titration curve that predicts a pKa value of 8.15 for the alpha-amino group of this intermediate. These data are considered relevant to discussions pertaining to a threonine dehydrogenase/2-amino-3-ketobutyrate CoA lyase enzyme complex in the threonine utilization pathway and to mechanistic aspects of the 5-aminolevulinate synthase-catalyzed reaction where 2-amino-3-ketoadipate is involved. PMID- 8439307 TI - Similarities between alanine dehydrogenase and the N-terminal part of pyridine nucleotide transhydrogenase and their possible implication in the virulence mechanism of Mycobacterium tuberculosis. AB - Recent developments in simultaneous multiple alignment methods of protein sequences allow prediction of structural similarity in related proteins. Alanine dehydrogenase and the N-terminal sequence of pyridine nucleotide transhydrogenase were compared for their sequences. High similarities of sequences were observed especially in their NAD(H)-binding sites. These similarities suggest that antibodies which recognized the alanine dehydrogenase of Mycobacterium tuberculosis can also be directed against the membrane bound pyridine nucleotide transhydrogenase. If this is the case, the virulent property of this pathogen could be linked to its higher synthesis of NADPH necessary for its anabolism. PMID- 8439308 TI - Chicken and mouse focal adhesion kinases are similar in structure at their amino termini. AB - A novel protein-tyrosine kinase, designated 'Focal Adhesion Kinase' (FAK), has recently been implicated in signal transduction pathways activated by extracellular adhesion molecules and by neuropeptide growth factors. Previously deduced primary structures for chicken and mouse FAK polypeptides differ at their amino-termini, with mouse FAK reported to have a 25 amino acid residue extension not present in chicken FAK. Additional sequence information from the 5'-end region of the chicken FAK transcript now indicates that the amino-terminal extension previously thought to be unique to mouse FAK is, in fact, also predicted for chicken FAK. Thus mouse and chicken FAK polypeptides appear to be structurally similar throughout their lengths. This is further supported by comparison of their electrophoretic mobilities. PMID- 8439309 TI - Complex I and complex III of mitochondria have common inhibitors acting as ubiquinone antagonists. AB - Mitochondrial complex I and complex III have common inhibitors with ubiquinone like structure. The tridecyl analog of stigmatellin, which inhibits mitochondrial complex III at nanomolar concentrations, also inhibits the NADH:ubiquinone reductase activity of complex I at micromolar concentrations. The inhibitor titer depends upon the concentration of the mitochondrial particles and extrapolates to 0.2 microM at zero particle concentration. The stigmatellin analog is more powerful than its parent compound and is noncompetitive with exogenous ubiquinones, rotenone and piericidin. Myxothiazol, which is another potent inhibitor of complex III, is also found to inhibit the activity of complex I with a titer comparable to that of the tridecyl analog of stigmatellin. Additionally, piericidin, which is the most powerful inhibitor of complex I, inhibits the ubiquinol:cytochrome c reductase activity of complex III at micromolar concentrations in mitochondrial particles and at submicromolar concentrations in the isolated enzyme complex. PMID- 8439310 TI - Cadmium and zinc mediated changes of the Ca(2+)-dependent endonuclease in apoptosis. AB - Isolated nuclei from mammalian cells contain a Ca(2+)-dependent endonuclease [1]. The produced DNA fragmentation is a necessary step in the sequence of events resulting in apoptosis [2]. We report here that zinc inhibits the DNA fragmentation in dependence of the free Ca2+ concentrations, suggesting that a balance between zinc and calcium might regulate the Ca(2+)-dependent endonuclease. Incubation of nuclei with different free calcium concentrations combined with cadmium shows a stronger inhibition of the DNA fragmentation than zinc. Cadmium inhibits the endonuclease in a calcium-independent way. Surprisingly cadmium alone is able to stimulate the endonuclease, thus to replace Ca2+. PMID- 8439311 TI - Smooth muscle alpha-actin promoter activity is induced by serum stimulation of fibroblast cells. AB - Transient transfection analysis of a plasmid containing human alpha-actin promoter linked to bacterial chloramphenicol acetyl transferase (CAT) reporter gene, in Rat-2 fibroblast cells, indicates that smooth muscle (sm) alpha-actin promoter activity is induced by serum. The CArG [CC (A/T) 6GG] box sequences within the alpha-actin promoter mediate the serum induction. This induction can be blocked by overexpression of Fos, suggesting that it follows the same regulatory pathway as c-fos. PMID- 8439312 TI - The effect of copper ion on arachidonic acid metabolism in the porcine corneal epithelium. AB - The effect of copper ion on arachidonic acid metabolism in the corneal epithelium was studied. Our results showed that when 3H-arachidonic acid (1 microCi/microgram) was incubated with homogenate of corneal epithelium at 37 degrees C for 45 min., three metabolites were formed. Metabolite A, the major metabolite, was identified as 12-HETE by HPLC and GC. An analysis with chiral phase HPLC revealed that metabolite A was a (R)-enantiomer. The production of 12(R)-HETE was stimulated by low concentrations of CuCl2 (< 0.1 mM) and inhibited by higher concentrations of CuCl2. Study on the biological activity of 12(R)-HETE showed that it could stimulate migration of endothelial cells in a concentration as low as 10 ng/ml. These results suggest that one of the effects of copper ion on the corneal neovascularization may be to regulate the level of 12(R)-HETE. PMID- 8439313 TI - Purification of calreticulin-like protein(s) from spinach leaves. AB - In a search for the plant equivalent of calsequestrin or calreticulin, the high capacity, low affinity Ca2+ binding proteins of muscle and non-muscle cells thought to play important roles in Ca2+ storage, we purified two Ca(2+)-binding proteins from spinach leaves. The proteins had apparent molecular weights of 55 and 53 kDa. On Western blot, they did not react either with anti-rabbit skeletal muscle, anti-dog cardiac muscle calsequestrin or anti-rabbit or anti-rat liver calreticulin antibodies, indicating that they were antigenically distinct. Periodic acid Schiff staining (PAS) revealed that the larger protein was glycosylated while the 53 kDa one was PAS-negative. When the proteins were subjected to NH2-terminus amino acid sequencing, the 55 and 53 kDa proteins turned out to be identical, thus probably representing different isoforms of the same protein. Comparison with published amino acid sequences of calreticulin reveals regions of similarity indicating that the plant Ca(2+)-binding proteins probably belong to the calreticulin family. PMID- 8439314 TI - Enhanced glutathione S-transferase 7-7 expression in rat hepatic cytosol following treatment with pyrrole. AB - Rat hepatic GST 7-7 expression in cytosol and in the S-hexylglutathione-agarose affinity purified fraction of cytosol from saline- (control) and pyrrole-treated animals was examined using metabolic activity, SDS-PAGE, immunoblot, and HPLC analyses. Metabolic activity of hepatic cytosol from pyrrole-treated animals was assayed using the substrates 1-chloro-2,4-dinitrobenzene, ethacrynic acid, and acrolein, and an approximately 1.5-, 1.2-, and 1.3-fold increase, respectively, was monitored in the rate of GST-catalyzed substrate conjugation to reduced glutathione. SDS-PAGE and immunoblot analysis using Class Pi GST-specific IgG confirmed that the GST 7 subunit was expressed in hepatic cytosol and in the affinity purified fractions from pyrrole-treated rats. In contrast, the GST 7 subunit was below the limit of detection in hepatic cytosol of saline-treated animals. HPLC analysis demonstrated the presence of the GST 7 subunit in the affinity purified fraction from pyrrole-treated rat hepatic tissue and showed that the level of this subunit was increased approximately 8-fold relative to the barely detectable level present in control tissue. N-terminal amino acid sequencing analysis confirmed the identity of the HPLC peak as GST 7-7. GST subunits 3, 1a, and 1b were elevated approximately 1.7-, 2.0-, and 2.4-fold respectively, in response to pyrrole treatment. These data provide evidence that pyrrole treatment results in de novo expression of GST 7-7 in rat hepatic tissue and suggest that pyrrole-containing compounds potentially generated during disease and/or altered heme metabolism, or those ingested in food products, may alter GST expression in hepatic tissue. PMID- 8439315 TI - Adenosine diphosphate ribulose in human erythrocytes: a new metabolite with membrane binding properties. AB - Incubation of ADPribose with yeast phosphoriboisomerase resulted in the formation of an adenylic nucleotide that was identified with ADPribulose by mass spectrometry. Synthesis of [32P]ADPribulose from [32P]NAD+ by the combined activities of commercial NAD+ glycohydrolase and phosphoriboisomerase allowed us to use it as a labeled internal standard throughout the procedure of purification from trichloroacetic acid extracts of human red blood cells. ADPribulose was purified by means of three sequential reverse phase HPLC separations and its concentration in human erythrocytes was estimated to be 0.11 +/- 0.1 microM. Unsealed erythrocyte ghosts did not transform ADPribulose, which bound to specific membrane proteins with a trichloroacetic and formic acid-resistant binding. The labeled proteins were identified as spectrin, bands 3, 4.1, 4.2 and Glyceraldehyde 3-phosphate dehydrogenase on the basis of their relative mobilities on SDS-PAGE. PMID- 8439316 TI - Evidence for an indirect effect of nerve growth factor (NGF) on the ADP ribosylation of a 22 kDa rho-like protein in PC12 cells. AB - EDIN catalyzes the ADP-ribosylation of a 22 kDa protein, probably related to rho, in permeabilized PC12 cells in a time- and dose-dependent manner. Pre-treatment of the cells with nerve growth factor inhibits this EDIN-catalyzed ADP ribosylation, both in vitro and in vivo. This inhibition is largely prevented by the addition of K-252a. Nerve growth factor itself causes neither ADP ribosylation nor phosphorylation of this 22 kDa protein. These results suggest that the ADP-ribosylation of the rho protein is inhibited, albeit indirectly, by nerve growth factor treatment. PMID- 8439317 TI - Analysis of the distribution of protein binding DNA motives in the vicinity of the 3'-side chicken alpha-globin enhancer. AB - DNA-protein interactions in the vicinity of the 3'-side chicken alpha-globin enhancer were analyzed in vitro. Downstream of the three GATA-1 motifs which constitute the core enhancer, a 4th homology box, containing two further DNA binding motifs, was found by sequence alignment between duck and chicken. One was identified as being a fourth GATA-1 motif in opposite polarity, while the other contains a putative AP-1/NF-E2 binding site. In addition, it was found that several GGTGG motifs interacting with nuclear factors are interspersed between the different GATA-1 sites. When nuclear extracts from chicken erythroblasts transformed by an AEV ts-mutant (clone HD3) or from adult chicken erythrocytes were compared, different protein factors were found to interact with these DNA motifs in DNase I footprinting and electrophoretic retardation experiments. These results are discussed in terms of a general distribution of protein-binding DNA sequences and the presence of nuclear factors in the majority of globin and also some non-globin gene control regions. PMID- 8439318 TI - Cloning and expression of cDNA encoding human betacellulin, a new member of the EGF family. AB - Betacellulin (BTC) is a novel growth factor purified from the conditioned media of mouse pancreatic beta tumor cells and has been found to be a new member of the epidermal growth factor (EGF) family. The cDNA encoding human BTC has been cloned from a cDNA library prepared from human breast adenocarcinoma cell line MCF-7. The nucleotide sequence encodes a polypeptide which consists of 178 amino acid residues including a putative signal sequence, indicating that the structural organization of human BTC is similar to that of mouse BTC. The amino acid sequence of the human BTC precursor protein exhibits 79% similarity with that of the mouse precursor protein. The BTC gene was found to be expressed in several mouse tissues including kidney and liver as well as in a mouse beta tumor cell line and MCF-7 cells, suggesting that BTC might play a physiological role in normal tissues. PMID- 8439319 TI - Presence of a serine protease in the complement-activating component of the complement-dependent bactericidal factor, RaRF, in mouse serum. AB - A 100-kDa protein was isolated from the complement-activating component of mouse Ra-reactive factor. It generated a 29-kDa chain upon reduction. Partial amino acid sequences of the 29-kDa chain were determined after fragmentation with CNBr. A 386-bp-long probe was synthesized by the polymerase chain reaction with oligonucleotide primers designed by reference to the amino acid sequence. Using this probe, we cloned a 3.7-kb DNA from a mouse liver cDNA library. The amino acid sequence of the 29-kDa chain deduced from the nucleotide sequence of this cDNA was consistent with the amino acid sequences determined. The full sequence was found to have characteristics of a serine protease and exhibited 29% and 30% homologies with those of light chains of the C1r and C1s subcomponents of complement, respectively. PMID- 8439320 TI - Expression of bone morphogenetic protein in human adenocarcinoma cell line. AB - A subclone termed as HSG-S8 was previously isolated from human salivary adenocarcinoma cell line, HSG, and proliferated in a serum-free culture. When HSG S8 and parental HSG cells were transplanted into nude mice i.m. or s.c., both cells reproducibly induced adenocarcinoma. Furthermore, injection of HSG-S8 consistently induced formation of cartilage i.m. or bone s.c. in tumors, but did not parental HSG cells. The cytoplasm of HSG-S8 cells was specifically immunostained by anti-bone morphogenetic protein (BMP)-2 antibody. The conditioned medium of HSG-S8 cells contained a protein of M(r) 18,000 which specifically reacted with anti-BMP-2 protein antibody. Northern blot analysis also revealed that HSG-S8 cells expressed transcripts for BMP-2. On the other hand, parental HSG cells gave a very slightly positive signal only in Northern blot analysis. These results indicate that HSG-S8 cells synthesize and secrete BMP-2 protein, which is probably involved in the formation of cartilage and bone in the tumor tissues in nude mice. PMID- 8439321 TI - Human melanoma cells but not normal melanocytes express vascular endothelial growth factor receptors. AB - Vascular endothelial growth factor (VEGF) is a specific mitogen for endothelial cells in vitro and an angiogenic factor in vivo. Its role in other cell types is not yet clear. To explore its possible involvement in malignant transformation, we studied the expression of its receptors in normal and malignant melanocytes. Binding and cross-linking experiments showed that human melanoma cells but not normal melanocytes express VEGF receptors. Separation of reaction products by SDS PAGE demonstrated the presence of 125I-VEGF/receptor complexes of 180 and 165 kDa in the melanoma cells. A diffuse complex with a mass of approximately 235 kDa was also detected in some experiments. Heparin enhanced the binding of the radioactive ligand to the receptors of the WW94 and SW1614 melanoma cell lines. This binding was completely abolished by heparinase digestion and was restored by the addition of exogenous heparin, indicating that heparin-like molecules are necessary for ligand/receptor interaction. This study suggests that the aberrant expression of VEGF receptors is one of the phenotypic changes occurring in melanoma cells during malignant transformation. PMID- 8439322 TI - Microtubule-associated protein interactions with actin filaments: evidence for differential behavior of neuronal MAP-2 and tau in the presence of phosphatidyl inositol. AB - Microtubule-associated protein (MAP) interactions with actin were investigated by falling-ball viscometry. At 1-2 microM MAP-2 or tau, we obtained a critical gelation concentration for actin of 0.1 mg/ml. In the presence of phosphatidyl inositol, actin filament bundling was completely disrupted only when MAP-2 served as the cross-linker, whereas tau-induced bundling of actin was unaffected by phosphatidyl-inositol. This represents the first clear indication that MAP-2 and tau exhibit differential behavior in their interaction with cytoskeletal components. PMID- 8439323 TI - Wall shear stress rather than shear rate regulates cytoplasmic Ca++ responses to flow in vascular endothelial cells. AB - Recent evidence suggests that the vascular endothelial cell (EC) can sense the flow-rate over its surface and according to the information, regulates not only its own morphology and functions but also those of the surrounding smooth muscle and other tissues. There is now a discussion over which of the following mechanisms actually initiates the signal-transacting response of EC against flow: the mechanical shear deformation of the cell due to flow-oriented wall shear stress (tau), or the diffusional accumulation of vasoactive agonists on the cell surface modulated by wall shear rate (gamma) or both. To identify the relative importance of each mechanism, we examined quantitative changes in the cytoplasmic free Ca++ concentration ([Ca++]i) in cultured EC in the presence of the Ca++ mobilizing agonist ATP, i.e., a second messenger response of the internal signalling system, following the perfusion of two buffers with different viscosities (mu), which relates these factors as tau = mu gamma. The results of in vitro fluorescence photometry in EC with Fura-2 showed that the [Ca++]i level was enhanced with increase in the shear rate but to a greater extent with higher viscosity, and that the [Ca++]i levels at the same calculated level of shear stress were virtually identical, regardless of difference in shear rate and viscosity. This quantitative one-to-one relationship between the shear stress and the second messenger response suggests that wall shear stress rather than wall shear rate is the principal physical factor eliciting EC responses to flow. PMID- 8439324 TI - Characterization of the factor E1BF from a rat hepatoma that modulates ribosomal RNA gene transcription and its relationship to the human Ku autoantigen. AB - We have purified the DNA binding protein E1BF (Enhancer 1 Binding Factor) from the nuclei of Morris hepatoma 3924A. This protein, which consists of two polypeptides of 72 kDa and 85 kDa, binds to several DNA sequences involved in the regulation of rDNA transcription. UV-crosslinking studies show that interaction of the protein with DNA is primarily through the 72 kDa polypeptide. Purified E1BF can also modulate pol I-directed transcription in a cell-free systems derived from rat and mouse. E1BF is related to the human autoantigen Ku as demonstrated by immunological cross-reactivity with monoclonal antibodies directed against Ku p70 in Western blot and gel mobility shift assays. PMID- 8439326 TI - Evidence for a polarized efflux system for peptides in the apical membrane of Caco-2 cells. AB - The transport of two model peptides across confluent monolayers of human colon adenocarcinoma (Caco-2) cells was studied. In the case of AcPhe(NMePhe)2NH2, transport in the apical to basolateral direction was increased with increasing peptide concentration in the apical compartment. Transport was also increased in the presence of verapamil. In contrast, the flux of AcPheNH2 was neither concentration dependent nor affected by verapamil. Further, in the presence of verapamil, transport in the basolateral to apical direction was showed for AcPhe(NMePhe)2NH2 and again unchanged for AcPheNH2. These results are consistent with the presence of a saturable, apically polarized transport system in Caco-2 cells which serves to hinder transport in the apical to basolateral direction, increase flux in the basolateral to apical direction and shows substrate specificity for these model peptides. PMID- 8439325 TI - Phosphorylation of an acid-soluble nuclear protein in response to catecholamine in cultured rat cardiocytes. AB - Effect of norepinephrine on the phosphorylation of nuclear proteins was examined in cultured rat cardiocytes. Differential effects of phorbol esters, endothelin and platelet activating factor on the phosphorylation of a nuclear acid soluble fraction were evaluated. A specific phosphorylated nuclear acid soluble protein was identified in response to norepinephrine. The increase in phosphorylation in the norepinephrine-treated cardiocytes is significantly greater than 8 fold (p < 0.001) as compared to the control group. This nuclear acid soluble protein has a high content of serine (> 12%) as well as acidic amino acids (> 20%) which is distinctively different from the histones as analyzed by amino acid composition. The specific phosphorylation of this nuclear protein (Mr 31 Kda) can be induced by norepinephrine within 5 minutes, indicating of an early gene activation event which modulates nucleosomal structure by phosphorylation. PMID- 8439327 TI - An AP-1 enhancer mediates TPA-induced transcriptional activation of the chicken insulin-like growth factor I gene. AB - As a step to elucidate a role of protein kinase C(PKC) pathways in the regulation of insulin-like growth factor I(IGF-I) gene, we sought to determine whether the IGF-I gene promoter of chicken can be a target of regulation by PKC. An initial gene transfer study showed that, in a human cell line HepG2, the IGF-I gene promoter directs accurate transcription of IGF-I-luciferase fusion gene and enhances luciferase activity. Treatment of transfected cells with 12-o tetradecanoylphorbol 13-acetate(TPA) increased promoter activity of 2100 and 600bp 5'-flanking sequence 4.9- and 3.6-fold, respectively. Site-directed mutagenesis in the AP-1-like sequence located within the 600bp resulted in 91% loss of its TPA-induced promoter activity, and a gel mobility-shift analysis revealed that TPA-stimulation of HepG2 cells caused a dramatic increase in specific protein-binding to the AP-1-like sequence, suggesting that the sequence functions as an AP-1 enhancer. These observations support a direct role for PKC pathways in activating the IGF-I gene promoter in chicken. PMID- 8439328 TI - Thyrotropin receptor in non-thyroid tissues. AB - Thyrotropin receptor (TSH-R), the main target for the autoantibody in Graves' disease, has been thought to be a thyroid-specific protein. However, we successfully obtained the cDNA fragments of TSH-R from rat retro-orbital tissues and adipose tissues by using polymerase chain reaction methods. Sequencing has revealed that the nucleotide sequence of the cDNAs from these non-thyroid tissues was identical to that from the thyroid. TSH-R peptide antibody, which recognizes rat TSH-R, stained a 104 kDa protein from the retro-orbital tissues and the adipose tissues. The band was not detected with the antibody preabsorbed with the peptide. These results suggest that the message is translated to make a TSH-R protein even in these non-thyroid tissues. PMID- 8439329 TI - Induction of cytochrome P450 2E1 during chronic ethanol exposure occurs via transcription of the CYP 2E1 gene when blood alcohol concentrations are high. AB - Induction of cytochrome P450 CYP 2E1 during chronic ethanol exposure in rats has been reported by our laboratory to occur by a complex two step process. The first step occurs at relatively low blood alcohol concentrations and involves increases in CYP 2E1-dependent activities and apoprotein levels with no increases in steady state mRNA encoding CYP 2E1. The second step of this process occurs at higher blood alcohol concentrations and involves elevated mRNA levels. In this report, we demonstrate for the first time that CYP 2E1 induction by chronic ethanol is associated with increased CYP 2E1 gene transcription and is independent of gonadal factors. PMID- 8439330 TI - Membrane association of leucyl-tRNA synthetase during leucine starvation in Escherichia coli. AB - The influence of leucine starvation on the subcellular location of leucyl-tRNA synthetase in Escherichia coli was examined in a leucine auxotrophic strain by sucrose density sedimentation analysis. Analysis of the subcellular distribution of leucyl-tRNA synthetase activity revealed that during unrestricted growth, the leucine synthetase enzyme activity was found to be localized in the soluble protein fraction of the gradient. However, during restricted growth on low levels of leucine, leucyl-tRNA synthetase activity was localized in the cytoplasmic membrane fraction of the gradient. The transition from soluble to membrane association of the enzyme also occurred following inhibition of protein synthesis by treatment of cells with chloramphenicol. These results collectively suggest that leucyl-tRNA synthetase may be recruited to the cytoplasmic membrane in response to shortages of leucine or perturbation of protein synthesis. PMID- 8439331 TI - Chloroquine allows to distinguish between hepatocyte lysosomes and sinusoidal cell lysosomes. AB - We have examined the effect of chloroquine on rat liver lysosomal enzyme distributions after isopycnic centrifugation in a sucrose gradient. Chloroquine injection causes the large majority of cathepsin C, acid phosphatase and N acetyl glucosaminidase to migrate towards lower density regions; on the other hand only about 50% of arylsulfatase and acid deoxyribonuclease are subjected to such a density shift. To specifically mark hepatocyte lysosomes and sinusoidal cell lysosomes, rats were injected with galactosylated bovine serum albumin (A) or mannosylated bovine serum albumin (B) labelled with 125I tyramine cellobiose; A is selectively endocytosed by hepatocytes, B by sinusoidal cells. The radioactivity distribution is affected by chloroquine in the same way as cathepsin C, after injection of A though it is not influenced by chloroquine after the injection of B. These results show that chloroquine does not modify the density of liver sinusoidal cell lysosomes when it decreases the density of hepatocyte lysosomes. Such a difference could result from the fact that sinusoidal cell lysosomes do not accumulate chloroquine to the same extent as hepatocyte lysosomes. Chloroquine treatment could be useful to distinguish between hepatocyte lysosomes and sinusoidal cell lysosomes. PMID- 8439332 TI - Identification of the fatty acid binding site on glutathione S-transferase P by immobilization to fatty acid-linked sepharose. AB - The association of glutathione S-transferase P (GST-P) with various fatty acids was confirmed by gas-liquid chromatography and mass-spectrometry. Palmitic and stearic acids were the major fatty acids bound to the enzyme in which the molar ratio was 1:0.8 (GST-P:fatty acid). To evaluate the association with respect to the fatty acid carbon chain length and identify the binding site, we prepared a series of fatty acid-linked Sepharoses. GST-P tightly bound the fatty acid-linked Sepharoses (CH3(CH2)nCOOH, n = 4 approximately 16), and the site was determined to be residues 121-156 from the amino terminus by tryptic digestion of GST-P bound to a fatty acid-linked Sepharose. By fatty acid affinity labeling, we identified the binding site as residues 141-188 (Biochem. Biophys. Res. Commun., in press). The overlapping hydrophobic residues (residue 141-156) is expected to be essential for the ligand binding site. PMID- 8439333 TI - Translocation of Ki-ras p21 between membrane and cytoplasm by smg GDS. AB - We have previously shown that smg GDS forms a complex with Ki-ras 4B p21 and thereby stimulates its GDP/GTP exchange reaction. We have shown here that smg GDS inhibits the binding of Ki-ras 4B p21 to membranes and induces the dissociation of prebound Ki-ras 4B p21 from membranes. Moreover, we have found that cotransfection of the smg GDS and Ki-ras 4B p21 cDNAs into COS7 cells increases the ratio of the cytosolic form of ras p21 to the membrane-bound form and the ratio of the GTP-bound form of ras p21 to the GDP-bound form. These results indicate that smg GDS regulates not only the GDP/GTP exchange reaction of Ki-ras 4B p21 but also its translocation between membrane and cytoplasm. PMID- 8439334 TI - Identification of a novel gamma-subunit from bovine brain GTP binding regulatory proteins (Gi/o). AB - Heterogeneity of the gamma-subunit of G proteins has been demonstrated by cDNA cloning and by partial sequence analyses. We have isolated two intact beta gamma subunit isoforms from bovine brain Gi/o mixture, in which only gamma subunits are distinct (Sohma, H., et al. (1992) Biochem. Biophys. Res. Commun. 184, 175-182). In this study, we isolated the gamma-subunit isoforms, gamma-I and gamma-II, and examined their amino acid sequences. Both gamma-I and gamma-II had blocked N terminal amino acid residues, and the terminal amino acids of both were able to be truncated by an acylamino-acid-releasing enzyme. Gamma-I seemed to be identical with the gamma-subunit reported elsewhere, while the gamma-II appeared to be a novel protein. Antibodies to synthetic peptides based on the part of the amino acid sequences of gamma-I and gamma-II reacted specifically to gamma-I and gamma-II, respectively. PMID- 8439335 TI - Congenitally defective aldosterone biosynthesis in humans: inactivation of the P 450C18 gene (CYP11B2) due to nucleotide deletion in CMO I deficient patients. AB - CYP11B2, the gene coding for steroid 18-hydroxylase (P-450C18), has been recently shown to be the same gene as that for corticosterone methyl oxidase type I and type II (CMO I & II) which were previously postulated to catalyze the final two steps in the biosynthesis of aldosterone in humans. Molecular genetic analysis of CYP11B2 of three patients affected with CMO I deficiency has revealed that deletion of 5 nucleotides occurs exclusively in exon 1, resulting in a frameshift to form a stop codon in the same exon. Thus, P-450C18 is not produced at all due to the mutation, causing a complete lack of aldosterone biosynthesis in the patients. Restriction fragment length polymorphism analysis has demonstrated that the patients are homozygous and the unaffected parent is heterozygous as for the mutation, indicating that CMO I deficiency is inherited in an autosomal recessive manner. These results provide the molecular genetic basis for the characteristic biochemical phenotype of CMO I deficient patients. PMID- 8439336 TI - Molecular cloning and sequencing of a cDNA encoding mung bean cytochrome P450 (P450C4H) possessing cinnamate 4-hydroxylase activity. AB - With the aid of partial amino acid sequences determined for cinnamate 4 hydroxylase (P450C4H) purified from mung bean seedlings, two cDNA clones were isolated and their inserts were completely sequenced. The nucleotide sequences of the two clones were nearly identical and contained an open reading frame predicted to encode a polypeptide consisting of 505 amino acid residues. The partial sequences determined from the purified P450C4H closely corresponded to the primary structures deduced from the cDNA sequences. This is the first isolation of cDNA clones encoding a higher plant P450 possessing clear physiological activity. Comparison to known cytochromes P450 indicated that P450C4H belongs to a novel P450 gene family. PMID- 8439337 TI - Activation by protein synthesis inhibitors of glucose transport into L6 muscle cells. AB - The effects of protein synthesis inhibitors on glucose transport into L6 myotubes was examined. Similar to the acute effects of insulin, short-term treatment with anisomycin or cycloheximide increased transport 2-fold. Kinetic studies demonstrated that this activation was due to a doubling in the Vmax values. The effects of anisomycin or cycloheximide were not additive to that of insulin. Both protein synthesis inhibitors caused only small increases in GLUT4 expression and negligible effects on GLUT1 expression. Anisomycin, as well as insulin, induced the translocation of both transporters from intracellular vesicles to the plasma membrane through not in quantities sufficient to entirely account for the activation of transport. The results indicate that protein synthesis inhibitors stimulate hexose transport in L6 myotubes by increasing the number of transporters in the plasma membrane and augmenting the intrinsic catalytic activity of the transporters. PMID- 8439338 TI - Cloning of alternately spliced mRNA transcripts coding for variants of ovine testicular follitropin receptor lacking the G protein coupling domains. AB - We report the cloning and characterization of two alternately spliced forms of ovine testicular follitropin receptor mRNA. A smaller receptor cDNA (151 A1) of 727 bp codes for a possible soluble receptor protein of 134 amino acids arising from exons 1-4 of the full length receptor. The 1.1 Kb cDNA clone (HK 18) extending up to the 8th exon codes for a mature protein of 259 amino acids with a single membrane spanning domain predicted by hydropathy analysis. As these structures account for 34% and 61% respectively of the extracellular domain of the full length receptor, we suggest that their putative protein products are likely to possess moderate or high affinity binding sites of physiological significance. PMID- 8439339 TI - Functional epidermal growth factor receptor localizes to the postacrosomal region of human spermatozoa. AB - The human epidermal growth factor receptor was detected immunohistochemically in the postacrosomal region of ejaculated human sperm and, when immunopurified and exposed to [gamma-32P]ATP, was found to be autophosphorylated. Localization of an apparently enzymatically active epidermal growth factor receptor to spermatozoa suggests that epidermal growth factor receptor-ligand interactions may play a role in gamete physiology or in fertilization. PMID- 8439340 TI - Modification of cell surfaces by enzymatic introduction of special sialic acid analogues. AB - Taking advantage of the defined acceptor specificity of rat liver alpha 2,6 sialyltransferase, N-linked Gal beta 1,4GlcNAc-sequences of glycoconjugates at the plasma membrane of viable human erythrocytes and lymphoblastic IM-9 cells were modified to terminate in three NeuAc analogues endowed with special biochemical properties: sialidase-resistant 9-amino-NeuAc, O-acetylesterase resistant 9-acetamido-NeuAc and photolabile 9-azido-NeuAc. Incorporation of the latter analogues and of parent NeuAc proceeded to similar values, whereas 9-amino NeuAc yielded slightly reduced values. PMID- 8439341 TI - Decreased ubiquinone levels in tissues of rats deficient in selenium. AB - The effect of selenium deficiency (-Se) on the levels of ubiquinones in liver, heart, kidney, and leg muscle was studied in the rat. Levels of ubiquinone 9 and ubiquinone 10 in the liver of -Se rats were about 50% of the levels in selenium adequate animals. Both ubiquinones in the heart were about 15% lower in -Se rats. Only ubiquinone 9 was significantly lower in the kidney of -Se rats. There was no difference in ubiquinone levels in leg muscle. Glutathione peroxidase activity in the tissues of -Se rats was > 95% lower. It is concluded that Se, as an integral part of the enzyme glutathione peroxidase, may protect tissues from oxidative damage, thereby preserving the ability of the cells to synthesize ubiquinone and preventing ubiquinone from oxidative degradation. PMID- 8439342 TI - cdc2 kinase phosphorylation of desmin at three serine/threonine residues in the amino-terminal head domain. AB - Phosphorylation of desmin filament by cdc2 kinase induced a transition toward the depolymerized state of the filament. Sequence analysis of purified phosphopeptides derived from cdc2 kinase-phosphorylated desmin revealed that Ser 6, Ser-22 and Thr-64 in the N-terminal head domain were the sites phosphorylated. PMID- 8439343 TI - Biochemical genetics of glycogenosis type II in Brahman cattle. AB - Glycogenosis type II is an inherited lysosomal storage disorder caused by acid alpha-glucosidase deficiency. The disorder is inbred in Brahman cattle, and the incidence of carriers in Australian herds averages 15%. Affected animals are lethargic and die typically in the eighth or ninth month after birth. A complete lack of acid alpha-glucosidase synthesis was demonstrated in cultured fibroblasts and muscle tissue of affected animals. Moreover, the tissue was found to be devoid of acid alpha-glucosidase mRNA. Gross abnormalities of the acid alpha glucosidase gene itself were not detected by Southern blot analysis. These results suggest Brahman glycogenosis type II to be caused by a point mutation or a micro deletion/insertion in the acid alpha-glucosidase gene. PMID- 8439344 TI - Cloning and sequence analysis of hypothalamic cDNA encoding Xenopus preproneuropeptide Y. AB - Neuropeptide Y (NPY) consists of 36 amino acids and it constitutes one of the most conserved neuropeptides. Here we report the complete sequence of the first amphibian NPY precursor by cloning of a hypothalamic cDNA encoding Xenopus laevis preproNPY. The overall amino acid sequence identity between Xenopus and other known NPY precursor proteins ranges from 59% (fish) to 82% (chicken); a low degree of identity was found for the signal peptide sequence (32-75%) and for the carboxy-terminal peptide of NPY (CPON; 43-73%), while the NPY peptide sequence itself constitutes the most highly-conserved region (89-100%) within the preproNPY structure. PMID- 8439345 TI - Tyrosine kinase inhibitors suppress agonist-induced contraction in smooth muscle. AB - Because tyrosine kinases participate in diverse signalling pathways, we suspected that these enzymes might also participate in regulation of signal transduction in smooth muscle. Therefore, we studied the effects of geldanomycin, tyrphostin, and genistein, three structurally unrelated tyrosine kinase inhibitors, on receptor mediated and depolarization-mediated contraction in three different types of smooth muscle. Contraction elicited by stimulation of muscarinic receptors with carbachol, or by stimulation of alpha-adrenergic receptors with norepinephrine or phenylephrine were markedly (> 80%) and reversibly inhibited by tyrosine-kinase inhibitors. In contrast, only slight inhibition (20%) occurred in contractions elicited by K(+)-induced depolorization. Moreover, tyrphostin did not inhibit direct Ca(2+)-mediated activation of the contractile apparatus in preparations permeabilized with beta-escin. These results suggest the novel hypothesis that tyrosine kinases participate in regulation of signal transduction that is associated with receptor-mediated contraction of smooth muscle. PMID- 8439346 TI - Potent metabolic stimulation of septal gray and cerebral white matter in vivo by intraventricular endothelin and nitric oxide. AB - Endothelin-1 (ET) and sodium nitroprusside (SNP, which liberates nitric oxide, NO) were given alone or together into a lateral cerebral ventricle (icv) of anesthetized rats to assess their potential interaction on cerebral rates of glucose metabolism (autoradiographic [14C]deoxyglucose technique). ET (9 pmol) produced hypermetabolic effects ipsilaterally in the septal nuclei and periventricular white matter. NO lesioned the septum, which displayed neuronal damage and diminished metabolic activity, and evoked potent increases in glucose metabolism bilaterally in commissural and projection white matter tracts. Together, ET and NO had synergistic hypermetabolic effects in the hippocampal fimbria, but were antagonistic on the metabolic rate of the lateral septal nucleus and choroid plexus. The results reveal an extraordinary sensitivity in the metabolic rate of septal gray matter to ET and of white matter fibers to NO in vivo. Icv administration offers a useful approach for examination of the metabolic and toxicological properties of the novel neurotransmitter substances ET and NO on septal neurons, myelinated fibers, and choroidal epithelia. PMID- 8439347 TI - Critical role of a lipoyl cofactor of the dihydrolipoyl acetyltransferase in the binding and enhanced function of the pyruvate dehydrogenase kinase. AB - Mammalian pyruvate dehydrogenase kinase binds to the lipoyl domain region of the core structure forming dihydrolipoyl acetyltransferase (E2) subunits. The bound kinase has a greatly enhanced rate in phosphorylating E2-bound pyruvate dehydrogenase (E1) tetramers versus the rate at which resolved kinase phosphorylates dissociated E1. This E2-activated kinase function was completely prevented by selective alkylation of reduced lipoyl groups while kinase and E1 binding to the E2 core were retained. Selective removal of lipoyl cofactors from intact E2 by treatment with Enterococcus faecalis lipoamidase decreased kinase activity by 4-fold and caused selective release of a major portion of the kinase from E2 in a sucrose-step gradient procedure. Selective and reversible modification of the lipoyl groups of E2 subunits also allowed the kinase to be dissociated under mildly chaotropic conditions. Thus, the lipoyl prosthetic group on one of the two lipoyl domains of E2 subunits is critically important for maintaining E2-activated kinase function and contributes to binding of the kinase to E2. Since removal of the lipoyl group weakened kinase binding to E2 more than modifying lipoyl thiols, it is suggested that the hydrophobic inner portion of the lipoyl conjugate (i.e., lysine carbons and C1 to C5 of the lipoic acid) is important in the binding of the kinase. PMID- 8439348 TI - The role of interleukin-1 in disease. PMID- 8439349 TI - [Birth of an illness, exemplified by Meniere disease]. AB - Martin Luther's history and a case report by Grapengiesser in 1801 demonstrate that there were typical clinical manifestations of Meniere's disease long before Meniere's description. Luther suspected Satanic inflictions as cause of his disease; later on clinical pictures of this kind were interpreted as cerebral apoplectiform congestions, or as symptoms of a psychosis. It is Meniere's merit to have shown that lesions of the inner ear can cause deafness, tinnitus and vertigo without involving the middle ear, the acoustic nerve or the brain. The biography of Prosper Meniere (1799-1862) is briefly outlined. He made his pioneering observation between 1834 and 1838 when he had to attend to a young lady who after catching a cold presented with vertigo and deafness on both ears, and died 5 days later. He reported on this case in an annotation to his translation of W. Kramer's textbook on otology in 1848, but did not mention the vertigo. It was only in 1861 that he described the complete syndrome he had discovered, referring in detail to the case and the post mortem findings of 25 years ago to prove his hypothesis that lesions in the inner ear can cause such symptoms. Following his presentation a controversy prevailed for many decades about the question whether there is an idiopathic Meniere's disease or not. This is highlighted by quotations from the literature. The first audiogram-like picture of the hearing loss involving all frequencies was presented by Gradenigo in 1892.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8439350 TI - [Effect of auditory deprivation on maturation of auditory pathways in the rat]. AB - To examine the influence of an auditory deprivation on the maturation of the central auditory pathways we reared newborn rats until the age of 21 days in a sound-proof chamber and additionally sutured their pinnae. At the age of 21 days we reopened the outer ear channels and placed the young rats into a normal environment. Every three days we recorded brain stem auditory evoked potentials with clicks, 1-, 8- and 16 kHz tone pulses until the age of 45 days, at the age of 60 days for the last time. Additionally all animals underwent middle latency response audiometry. Only directly after reopening the ear channels the thresholds for 8 and 16 kHz were worse in the deprived animals than in the normal ones. For clicks and 1 kHz and all testings on the other days the mean threshold response of the deprived rats did not differ from that of the normal animals. Testing with clicks, the interpeak latencies (I-IV), that is the brain stem transmission time, were prolonged significantly between the 24th and the 36th day of life. Measuring with 1 kHz tone pulses we found a difference from the 30th to the 36th day. Testing with 8 and 16 kHz tone pulses the brainstem transmission time was significantly prolonged between the 21st and 33rd day of life. The middle latency responses showed large variances, there was no significant difference. After the 36th day of life all latencies had normalised. PMID- 8439351 TI - [Improved evaluation of transitory evoked otoacoustic emissions by correlation filtering]. AB - Hearing screening as well as evaluation of cochlear function under therapy with ototoxic agents or patients with various diseases is increasingly done by registration of transient evoked otoacoustic emissions (TEOAE). Usually the standard system ILO 88 Otodynamic Analyser is used, where until now emissions were analyzed subjectively. However, evaluation of signals may be difficult mainly in the hearing threshold area. In this article we describe a method to mathematically analyze registered emissions by correlation-filtering. This allows to better identify small specific responses, to further increase the sensitivity of TEOAE, and offers a more objective means for audiologic diagnoses. PMID- 8439352 TI - [Comparative studies of the ototoxicity of cisplatin and carboplatin]. AB - The application of the potent anticancer drug cisplatin is limited by major side effects such as its ototoxicity and its nephrotoxicity. Since carboplatin has been introduced into clinical use, a platinum derivative with less pronounced ototoxicity and nephrotoxicity is available. The aim of this study was to quantify the ototoxicity of carboplatin comparing it to cisplatin using the wellknown guinea-pig model. Using morphological and functional methods it could be shown that the ototoxic damage was by far higher in a group which had received a total dose of 12 kg cisplatin/kg than in a group which had received a dosage of 90 mg carboplat/kg. Our investigations show that the ototoxic potential of cisplatin in the guinea-pig is more than 9 times higher than that of carboplatin. PMID- 8439353 TI - [Soft laser therapy in combination with tebonin i.v. in tinnitus]. AB - 28 patients were treated with soft-laser therapy. Two-thirds of them had suffered from tinnitus for more than six months and had undergone different therapies before. Each patient was treated twelve times, treatment lasting ten minutes. Before therapy six ml of Tebonin were given i.v. Four minutes later, the laser was positioned at a distance of one centimetre from the patients' mastoid. The laser beam was directed two fingers above the mastoid tip aiming at the lateral wall of the contralateral orbit. Before and three weeks after treatment each patient underwent pure tone audiometry and determination of the tinnitus intensity. Patients were asked to score symptoms before and three weeks after therapy. Hearing levels before and after soft-laser therapy did not show any statistic difference. Three weeks after the last treatment, twenty patients denied any change in tinnitus. Two patients felt an improvement of tinnitus and one patient had recovered completely. Five patients remained undecided about the outcome of therapy. To sum up, according to our results, the trial so far failed to show clear benefits of soft-laser therapy for patients suffering from chronic tinnitus. PMID- 8439354 TI - [Transcranial magnetic stimulation in perioperative damage to the facial nerve]. AB - 5 patients (3 men, 2 women, aged from 28 to 51 years) with unilateral facial palsy after surgery of a cerebellopontine angle tumour have been investigated by transcranial magnetic stimulation. The purpose was to evaluate the prognostic aspects of this method, which was compared with the electrical stimulation of the facial nerve and the elicitation of an orbicularis-oculi reflex. The components of the blink reflex were absent in all cases. In 3 patients electrical stimulation was possible (compound muscle action potentials were delayed). With transcranial magnetic stimulation ipsilateral short-latency and contralateral long-latency responses (stimulation of the cortex) were elicited and registered from the M. mentalis as well as 3 times from the M. orbicularis oculi. The short latency response revealed no prognostic aspects. Despite the missing response, a recovery was possible. Long-latency responses could be evoked in all patients. The extent of delay in latency was strongly correlated with clinical improvement of the paresis. Interestingly, this correlation could also be observed in the single rami of the facial nerve when two muscles were investigated in a patient. Transcranial magnetic stimulation is an important improvement in electrophysiological diagnosis of perioperative lesion of facial nerve to prove continuity of the nerve and to evaluate the clinical course. PMID- 8439355 TI - [Ionomer cement in cochlear implant surgery]. AB - Ionomer-based cement is a new bone replacement material. After promising results have been obtained with this material in middle ear and skull base surgery as well as in plastic reconstructive surgery, this material can be used to fix a cochlear implant system (internal receiver as well as the electrode) to the temporal bone. This material is formed via a reaction of a glass powder with a polycarboxylic acid. The cement has a manipulation period of about 5 minutes. After setting, the cement is well tolerated by tissue and has the additional advantage of being biocompatible and permanently stable in a biological environment. The cement and the acid are commercially available as a two component capsulated system. In cochlear implant surgery this material is used to achieve a stable attachment of the internal receiver to the temporal bone. Displacement and damaging of the internal receiver and the electrode are prevented. PMID- 8439356 TI - [Topical anesthesia of the tympanic membrane and tubal function--is there a correlation?]. AB - The influence of topical anaesthesia of the tympanic membrane on Eustachian tube function was investigated using the pressure chamber impedance method, thus obtaining quantitative data. Anaesthesia was performed by application to the tympanic membrane of small cotton balls containing lidocaine and dimethylsulfoxide. We did not observe significant alterations of tubal parameters after unilateral or bilateral anaesthesia. Our observations are in contrast to investigations published by Nagai. We suppose that differences in methods of topical anaesthesia are responsible for this discrepancy. Our technique of topical anaesthesia of the tympanic membrane excludes any effect on the Eustachian tube, thereby avoiding negative consequences of middle ear pressure on wound healing. PMID- 8439357 TI - [Reconstruction of a malformed external ear by an endoprosthesis of porous polyethylene with an integrated suction system]. AB - Complete reconstruction of the external ear is one of the most difficult tasks in plastic and reconstructive surgery. The risk of frame protrusion inherent in all alloplastic materials is reduced by using a new premoulded endoprosthesis with an integrated suction system. It consists of tissue-compatible porous polyethylene. A conventional suction drainage can be attached to a hollow canal system within the endoprosthesis that empties from defined spaces corresponding to the natural concavities of the external ear. In combination with a preceding expansion the overlying skin is then adapted evenly and completely to the frame by suction. As a result of this vacuum seromas and haematomas can be prevented. Furthermore, infections and pressure necroses due to matress sutures cannot develop. The use of this endoprosthesis obviates the removal of autogenous cartilage and all the complications and scars that are connected with this procedure. The frame itself is stable and has a relief that is largely similar to the natural form of the auricle. Thus, an aesthetically satisfying result can be achieved also in the hand of the surgeon who is not often engaged in this field of plastic surgery. PMID- 8439358 TI - [Surgery of cholesteatoma of the ear canal]. PMID- 8439359 TI - [The effect of age on inhibition of visual fixation of the rotatory-induced nystagmus reaction]. AB - The interactive functions between sensory systems show changes that depend on the development of the growing body. Important conditions for the development of the visual suppression of vestibular evoked nystagmus reactions are the maturation of the visual system, the presence of a functioning vestibular system and close connections between both systems. Response to vestibular, visual and combined vestibular and visual stimulation does not only change during early childhood. We have also learnt from studies of adults of different ages that there are characteristic changes in nystagmus reactions to vestibular stimulation, in optokinetic reactions and in vestibular-spinal functions during the whole period of life. 272 randomly selected neuro-otologic routine patients aged between one year and four months and eighty-eight years and ten months were included in the study to analyse age-related changes of visual suppression during rotatory stimulation. The rotatory stimulation consisted of an sinusoidal stimulus pattern with amplitudes of +/- 180 degrees and a period duration of 20s. The vestibular stimulation was performed in total darkness and with a visual target which was attached to the chair in front of the patient's eyes. The results of this study demonstrate that the amplitudes of nystagmus reactions, evoked by sinusoidal harmonic acceleration, can be quantitatively suppressed by visual fixation. The degree of suppression depends on age. The fixation indices provide the ability to measure the degree of this suppression in percent. The trend to better fixation suppression increases up to the end of the age of forty. The ability to suppress vestibular nystagmus decreases, however, after reaching the fortieth year of life. The analysis of smooth pursuit shows after the sixtieth year of life a continuous rise in the number of saccades with increasing age. These changes are caused by aging processes in cerebral tissues which lead to functional changes e.g. in the interactive functions between sensory systems. PMID- 8439360 TI - Prevention of deafness and hearing impairment. Interview by Barbara Campanini. PMID- 8439361 TI - The state opts out, the people opt in. PMID- 8439362 TI - Urban community health volunteers. AB - An evaluation was made of the effectiveness of an urban community health volunteer programme in Pokhara, Nepal, in sensitizing and motivating people for the improvement of health knowledge and skills and the use of services. Despite weaknesses and inadequate management support, there has been a sharp increase in coverage by the health services. If management support were properly developed the programme could undoubtedly play a vital role in raising health standards. It was clearly demonstrated that the utilization of services can be increased if access to them is improved. PMID- 8439363 TI - Group learning by mothers about primary health care. PMID- 8439364 TI - The very young as agents of change. PMID- 8439365 TI - Ethics of drug trials in developing countries. PMID- 8439366 TI - Drug trials in developing countries: the need for ethics. AB - Drug trials in developing countries may contribute to a better understanding of the properties of antirheumatic drugs. Before this can be done, however, there is a need for ethical committees to oversee the trials and for effective regulation of drug availability. PMID- 8439367 TI - No relaxation on drug safety and efficacy. AB - The background and current status of legislation and practice relating to drug certification in Canada are examined. An outline is given of procedures introduced to handle the growing workload faced by the regulatory authority. PMID- 8439368 TI - Who really cares for Africa? AB - The destiny of all the peoples in the world is today, more than ever before in recorded history, linked closely together. This is why the traditional political, economic and social divisions that were created to promote self-interest at the expense of others can no longer be tolerated. The author gives some examples of the obstacles to progress in Africa and other developing countries, and calls for a truly new world order based on justice and equity. PMID- 8439369 TI - Epidemiology teaching and the community perspective. PMID- 8439370 TI - Which way for malaria control and epidemiological services? AB - Historically epidemiological services were intimately linked with malaria control, and both were conceived as an integral part of local public health services. The strategy of malaria eradication between 1956 and 1969 moved malaria activities away from the health services and led to a weakening of epidemiological capacities. The epidemiological requirements of malaria control are now greater than ever. However, the capacity of health services to fulfil these requirements remains seriously weak. Investment in malaria control could provide an important building block for the much-needed strengthening of national public health. PMID- 8439371 TI - Citizens' action for public health. AB - The European Public Health Alliance aims to ensure broad participation in health related policy-making and to contribute to the promotion of public health. The origins of the Alliance and the ways in which it relates to official bodies are outlined below. PMID- 8439372 TI - Piped water for rural houses. PMID- 8439373 TI - A computer program on worldwide tobacco consumption. PMID- 8439374 TI - Sexual discrimination hits women's health. PMID- 8439375 TI - Family planning education by radio. PMID- 8439376 TI - Safer motherhood now in Sevagram. PMID- 8439377 TI - Nurses as drug prescribers in rural areas. PMID- 8439378 TI - Chronic back pain. PMID- 8439379 TI - Basic requirements for hospital equipment. PMID- 8439380 TI - Eye drops for rural populations. PMID- 8439381 TI - Use of night soil in agriculture and fish farming. AB - The use of untreated night soil as a fertilizer in agriculture or as a source of nutrients in fish farming presents a considerable health hazard in the form of pathogens and parasites. A pilot study is reported in which night soil was placed in an anaerobic digester, producing biogas and residual organic matter. The latter was introduced into biostabilization ponds, and nutrients were thus obtained for the rearing of fish. Fish ponds receiving nutrients derived from treated night soil were less contaminated than ones to which untreated night soil was applied, and the fish reared in them were of superior quality. PMID- 8439382 TI - Telemedicine in rural Norway. AB - Trials are reported from Norway on the use of videoconference facilities to make remote diagnoses in the fields of pathology, dermatology, otorhinolaryngology, cardiology and radiology. Telemedicine is moving from the experimental stage to become a regular feature of practice. PMID- 8439383 TI - What future for traditional Chinese medicine outside China? AB - In certain countries of east and south-east Asia, traditional Chinese medicine continues to be used by many people. However, the pattern of use favours the advance of the drug-retailing side of this sector rather than medical care, and there is consequently some concern about the professional status of practitioners in the long term. PMID- 8439384 TI - Planning and management of change in health systems. AB - The modernization of a health system may require priorities to be defined and the responsibilities of staff at the periphery to be increased. With a view to achieving these objectives, senior personnel from Guinea-Bissau's Ministry of Health participated in a seminar on mission mapping, the nature of which is outlined below. PMID- 8439385 TI - Birth control vaccine research. PMID- 8439387 TI - Tuberculosis on the increase. PMID- 8439386 TI - Resurgence of yellow fever. PMID- 8439388 TI - Site selection for new hazardous waste management facilities. PMID- 8439389 TI - Platelet monoamine oxidase B activity in Parkinson's disease: a re-evaluation. AB - An increase in platelet monoamine oxidase (MAO) B activity in drug-free parkinsonians (n = 6) compared with healthy controls (n = 10) has been confirmed using both phenylethylamine (PEA) and dopamine as substrates, reaching statistical significance in the case of PEA oxidising activity (p < 0.05). Thus, certain reports of raised platelet MAO B activity towards PEA but decreased activity towards dopamine in parkinsonians, raising the possibility of the existence of an abnormal form of MAO B in this condition, cannot be supported. PMID- 8439390 TI - The effects of L-threo-3,4-dihydroxyphenylserine on the total norepinephrine and dopamine concentrations in the cerebrospinal fluid and freezing gait in parkinsonian patients. AB - We studied the effects of L-threo-DOPS (L-DOPS) on the concentrations of total (conjugated and unconjugated) dopamine (DA) and norepinephrine (NE) in the cerebrospinal fluid (CSF) of parkinsonian patients with freezing phenomenon. The NE concentration increased remarkably and dose-dependently after administration of L-DOPS in both L-dopa/carbidopa-pretreated and untreated patients. The DA concentration also increased mildly but significantly in L-dopa/carbidopa untreated patients. Freezing phenomenon improved in 6 out of 8 patients at Hoehn and Yahr's stage III, and 1 out of 5 patients at stage IV. These results indicate that L-DOPS administration increases the NE concentration dose-dependently, and is effective for freezing of gait of moderate severity. PMID- 8439391 TI - Speed and power of higher cerebral functions in parkinsonian patients. AB - We compared 21 idiopathic, pharmaceutically well managed parkinsonian patients, neurological stages I and II on the Hoehn and Yahr scale with 21 parkinsonian patients stage III and 19 healthy controls group-matched for age, sex and education to study to what extent impairments of fluid intelligence in parkinsonian patients are due to a slowing of cognitive processes, i.e. to bradyphrenia (a deficit in the speed component) or to a true performance deficit (a deficit in the power component). The Vienna Matrices Test, which is similar to Raven's Standard Progressive Matrices was presented to the patients in a modified form. The Cognitrone was used to measure the influence of vigilance and perception on the cerebral function assessed. With increasing neurological severity of the disease, the dimension examined showed true deficits in the power component. There was no bradyphrenia in the sense of slower performance which would otherwise be equal to that of the control subjects. Vigilance and perception did not change in the course of the disease. PMID- 8439392 TI - Value and appropriate use of rating scales and apparative measurements in quantification of disability in Parkinson's disease. AB - Despite widespread use in pharmacotherapeutical trials, in the majority of rating scales used in Parkinson's disease (PD) validity, reliability and appropriate use have never been confirmed by statistical data. For this reason 350 unselected PD pats. were investigated by an extensive standardized test-battery including registration of basis data, Columbia University Rating Scale (CURS), scale for assessment of functional disability (ADL), SCAG-scale, Hoehn & Jahr-scale (HY), mod. Webster step second-test (WSST), Purdue-pegboard, questionnaire for subjective complaints (SC), WDG, LPS1/2, 3/4, 6, 7, 10, clinical assessment of dementia, v. Zerssen-scale and orthostatic hypotension (60 degrees tilt up). For CURS, SCAG and ADL instrumental reliability was calculated by Cronbach's alpha. For CURS, SCAG, ADL and the total data of complete test battery (CTB) principal component analysis (PCA) was performed for data reduction. CURS, SCAG and ADL showed high internal consistency (alpha approximately > or = 0.9). For CURS 5 factors accounting for 66% total variance could be extracted by PCA. They represent gait, rigidity, tremor, right/left dexterity (eigenvalues > 1). For SCAG 3 factors (61% of total variance) representing dementia, depression and change of personality were extracted. For ADL 3 factors (67% of total variance) could be extracted, representing overall functional disability, handwriting and disability by pain. PCA of the CTB identified 8 interpretable factors (66% of total variance) characterizing at least partially the clinical profile of PD: 1. motor disability (assessment by rating-scales) 2. dementia, 3. motor-disability (assessment by apparative measurements), 4. depression, 5. orthostatic hypotension, 6. WDG, 7. tremor and 8. pain. Our data confirm the suitability of the investigated scales and give a rational base for their appropriate use in a sense of data reduction and economical evaluation. PMID- 8439393 TI - Sequencing of exons 16 and 17 of the beta-amyloid precursor protein gene reveals the beta-amyloid sequence to be normal in cases of the parkinson dementia complex of Guam. AB - Exons 16 and 17 of the beta-amyloid precursor protein gene has been sequenced in individuals with the amyotropic lateral sclerosis/Parkinson's dementia complex of Guam to test the hypothesis that this disease is an allelic variant of Alzheimer's disease and to test whether sequence differences within beta-amyloid in this population contributes to the non-deposition of this peptide in the disorder. The sequence was normal. PMID- 8439394 TI - A molecular approach to Alzheimer's disease. PMID- 8439395 TI - Primary structure of the hinge region in adult chicken cardiac myosin subfragment 2. AB - The complete amino-acid sequence of the hinge region in the subfragment-2 (S-2) derived from adult chicken cardiac ventricular muscle myosin has been determined by direct protein sequencing. The entire amino-acid sequence of this hinge composed of 143 residues was established by structural analysis of CNBr peptides, lysyl and arginyl endopeptidase peptides of carboxymethylated S-2. By sequence comparison with the corresponding region of the same chicken cardiac myosin which was recently deduced from its cDNA eight amino-acid differences were recognized. Comparing the sequence of this hinge with those of other cardiac myosins such as rat alpha- and beta-myosin heavy chains (MHC), rabbit alpha-MHC and human alpha- and beta-MHCs relatively lower degrees of sequence identities, namely 74.8%, 77.6%, 76.1% 75.5% and 75.5%, are observed. On the other hand, more than 89.5% sequence identities are shown among these mammalian cardiac myosins. These results indicate that avian cardiac MHC has diverged earlier than mammalian cardiac myosin has diverged to alpha- and beta-MHC. Amino-acid substitutions in this hinge region form a cluster on the C-terminal sequence region. On the contrary, in the N-terminal portion, completely conserved segments are observed, suggesting that these regions may contribute to the myosin ATPase activity and muscle contraction. PMID- 8439396 TI - Effects of the phenacetin metabolite 4-nitrosophenetol on glycolysis and pentose phosphate pathway in human red cells. AB - Human erythrocytes exposed to 4-nitrosophenetol showed marked alterations of their endogenous metabolism. Rapid ferrihemoglobin formation mediated by the NADPH-dependent enzymic cycling of the nitrosoarene ("Kiese cycle") and extensive GSSG production caused an immediate drain of G-6-P into the pentose phosphate pathway at maximal flow. Despite a 2.4-fold increase in glucose phosphorylation rate and a branching ratio of 97:3 between pentose phosphate pathway and Embden Meyerhof pathway, the G-6-P supply was obviously insufficient to meet the immense NADPH demand. Thus, a significant recycling of pentose phosphate pathway-derived F-6-P was observed in the order of 65%. Comparison of NADPH regeneration and ferrihemoglobin formation indicates the "Kiese cycle" to be a minor mechanism in ferrihemoglobin production in the case of high 4-nitrosophenetol concentrations. Most probably, reactive intermediates of 4-nitrosophenetol other than N-hydroxy-4 phenetidine, i.e. bicyclic arylamines and glutathione S-conjugates are formed which produce ferrihemoglobin without involvement of NADPH. The experiments have shown that red cells are remarkable robust to tackle the massive oxidative stress as elicited by 4-nitrosophenetol. The immediate metabolic response of the pentose phosphate pathway allows rapid regeneration of reduced glutathione. Thereby, SH containing enzymes are effectively protected and/or regenerated and hemolysis is kept minimal. Hence, red cells are favourably suited for clearing the blood from N-oxygenated arylamines before they can reach more sensitive target organs. PMID- 8439397 TI - Effects of the phenacetin metabolite 4-nitrosophenetol on the glutathione status and the transport of glutathione S-conjugates in human red cells. AB - The extent of ferrihemoglobin formation in human erythrocytes by 4 nitrosophenetol and its metabolisation rate strongly depended on the availability of cellular GSH. Ferrihemoglobin formation rate was increased by inhibition of the red cell glutathione reductase, and 4-nitrosophenetol disappeared more slowly. When red cells were completely depleted from SH groups, ferrihemoglobin formation was retarded, despite 4-nitrosophenetol was hardly metabolized. In turn, the glutathione status of human red cells was strongly affected by 4 nitrosophenetol. GSSG, which was produced in large amounts, was reduced, as long as the reducing system was intact. The decreased total glutathione content, however, did not recover completely, indicating formation of stable glutathione S conjugates. The active export of the stable model glutathione thioether S-(2,4 dinitrophenyl)glutathione was strongly inhibited by 4-nitrosophenetol. A Lineweaver-Burk plot of the transport data suggested a competitive inhibition mechanism, presumably caused by glutathione adducts. The results indicate that the strong pi-donor substituent in 4-nitrosophenetol enables metabolic reactions with glutathione, producing biological effects hitherto not observed with nitrosobenzene. Bicyclic arylamines and glutathione S-conjugates may cause ferrihemoglobin formation that is not brought about by the diaphorase reaction. The latter may be responsible for transport inhibition of GSSG and other glutathione S-conjugates. PMID- 8439398 TI - Divergent binding sites in pyruvate kinases I and II from Escherichia coli. AB - Pyridoxal 5'-phosphate incorporation into pyruvate kinase II from E. coli was decreased by the substrate phosphoenolpyruvate and increased by the allosteric activator ribose 5-phosphate, the total incorporation being linearly related to inactivation. Four lysyl residues were substantially modified, whatever the incubation conditions were while two additional residues became reactive only in the presence of the allosteric activator. Six tryptic peptides containing modified lysines were purified and sequenced. They defined five regions of pyruvate kinase II, since one of them contained two labelled lysines and included a peptide which also appeared independently. Sequence comparison with E. coli type I, yeast and cat muscle pyruvate kinases shows that the binding regions of pyruvate kinase II are clearly divergent from those of pyruvate kinase I and of the eukaryotic enzymes. PMID- 8439399 TI - A convenient spectrophotometric method for measuring the kinetic parameters of glyceryl-ether monooxygenase (EC 1.14.16.5). AB - Details of a direct spectrophotometric method for assaying glyceryl-ether monooxygenase activity are described. The assay has several advantages over previous methods including the convenient determination of the kinetic parameters of lipid substrates and tetrahydropterin cofactors with acceptable accuracy. The apparent Km and Vmax values have been measured for 6-methyl- and 6,7-dimethyl 5,6,7,8-tetrahydropterins and 6R-tetrahydrobiopterin as well as twelve lipid ethers including lyso-PAF (platelet activating factor), and the V/K values are a better index for comparing substrate efficiencies. The monooxygenase activities of a variety of assorted lipids are also compared with RS-batyl alcohol, some of which are weak inhibitors. The effects on monooxygenase activity by various concentrations of six detergents are compared and showed that Mega-10 is the most satisfactory for solubilising alkyl ether substrates at low concentrations (ca. 0.08%) of detergent. The syntheses of a variety of ether lipids used in this work, together with their 1H-NMR and IR spectra, are described. PMID- 8439400 TI - Evaluation of collagen cross-linking techniques for the stabilization of tissue matrices. AB - The use of glutaraldehyde (GTA) for cross-linking biological tissue implants has a number of undesirable side effects, including cytotoxicity and induction of calcification. In an attempt to find an improved cross-linking agent for tissue implants, we have evaluated a number of cross-linking procedures shown previously to be effective with pure collagen or collagenous substrates, including GTA, succinic anhydride, cyanamide, 1-ethyl-3-(dimethylaminopropyl)carbodi-imide, dimethyl suberimidate, ascorbate-copper, glucose-lysine and acyl azide treatments. Apart from GTA, only acyl azide treatment significantly cross-linked human dermis, the degree of cross-linking being better than that seen after treatment of dermis with 1 mM GTA. Acyl azide treatment of thicker vascular tissue (porcine aorta) also resulted in a significantly cross-linked tissue. Preliminary cytotoxicity studies suggested that acyl azide treatment was not toxic, and, therefore, coupled with its cross-linking ability, this treatment is worthy of further investigation and may prove to be an alternative to GTA for the treatment of bioprostheses. PMID- 8439401 TI - The application of lux genes. PMID- 8439402 TI - Encapsulation of the cobra cytotoxin P4 in liposomes. AB - Cytotoxin P4 isolated from the venom of the cobra Naja nigricollis nigricollis was encapsulated in liposomes by the reverse-phase evaporation method using phosphatidylcholine, cholesterol and phosphatidylethanolamine at molar ratios of 3:1:1. Cytotoxicity examination on murine melanoma B16F10 revealed that the activity of the entrapped cytotoxin did not change significantly and remained stable for at least 1 year at 4 degrees C without any significant leak from the liposomes (< 1%). Moreover, the activity of the cytotoxic liposomes was 20-fold higher towards human erythrocytes. Whereas 45 micrograms of the free cytotoxin/ml were needed for total haemolysis, the cytotoxic liposomes brought about the same effect at cytotoxin concentrations of 2-2.5 micrograms/ml, indicating the potential of the liposomes as a delivery system for the snake toxin. PMID- 8439403 TI - Sugar-coated liposomes: a novel delivery system for increased drug efficacy and reduced drug toxicity. AB - The uptake of glycoside-bearing liposomes by macrophages has been studied in vitro. Since the uptake was found to be specific for the end sugar attached to the glycoside, the possibility is raised that glycoside-bearing liposomes might be used in vivo as systems to deliver drugs to macrophages. Using the antileishmanial drug urea stibamine, these delivery systems have been tested in vivo against model leishmaniasis. The results indicate that the drug encapsulated in sugar-coated liposomes is much more potent in comparison with normal liposome encapsulated drug or to the free drug. Mannose-grafted liposomes are more efficient in transportation of drugs compared with those bearing glucose. Toxicity studies involving blood parameters, histological staining of tissues and specific enzyme activities related to liver function, show no apparent toxicity with the drugs. Hence, drug encapsulated sugar-coated liposomes may have possible applications to humans. PMID- 8439404 TI - Immobilization of beta-glucosidase from Penicillium funiculosum on nylon powder. AB - beta-Glucosidase from Penicillium funiculosum was immobilized on nylon powder previously activated with triethyloxonium tetrafluoroborate, 1,2-diaminoethane and glutaraldehyde. The activation of the nylon powder and the immobilization processes were studied and optimized for the enzyme and the matrix. A high activity retention (67%) was obtained using the activation and immobilization conditions finally selected. PMID- 8439405 TI - Hydrolytic properties of two cellulases of Trichoderma reesei expressed in yeast. AB - Two cellulases of the filamentous fungus Trichoderma reesei, cellobiohydrolase II (CBHII, EC 3.2.1.91) and endoglucanase I (EGI, EC 3.2.1.4), produced in recombinant strains of the yeast Saccharomyces cerevisiae, were tested in the hydrolysis of cellulose, xylan and other polymeric substrates. Both enzymes were active against unsubstituted, insoluble cellulose. CBHII had greater activity than EGI against crystalline cellulose, whereas in the case of amorphous substrate the order was reversed. Evidence for synergism was obtained when mixtures of the two enzymes were used with a constant total protein dosage. The EGI was also active against soluble substituted cellulose derivatives, whereas the activity of CBHII against these substrates was insignificant. Both enzymes were active against barley (1-->3,1-->4)-beta-glucan, but were inactive against (1-->3,1-->6)-beta-glucan (laminarin). An apparent low mannan-degrading activity of EGI against locust-bean (Ceratonia siliqua) gum galactomannan was not confirmed when homopolymeric mannan was used as substrate in a prolonged hydrolysis test. EGI exhibited considerably greater activity against insoluble, unsubstituted hardwood xylan than against amorphous cellulose. Soluble 4-O-methyl glucuronoxylan was also attacked by EGI, although to a somewhat lesser extent than the unsubstituted xylan. By comparison with two purified xylanases of T. reesei, EGI produced xylo-oligosaccharides with a longer mean chain length when acting on both substituted and unsubstituted xylan substrates. CBHII was inactive against xylan. PMID- 8439406 TI - Calbindin D-28K and NADPH-diaphorase activity are localized in different populations of periglomerular cells in the rat olfactory bulb. AB - Calbindin D-28k (CaBP) immunocytochemistry and NADPH-diaphorase (ND) histochemistry have been combined in the rat olfactory bulb by successive incubations of the same sections. The outer strata showed a similar neuronal staining pattern for both markers with positive periglomerular neurons (although the CaBP-stained periglomerular cells were six-fold more abundant than the ND active ones) and larger neurons scattered in the glomerular and external plexiform layers. Both populations of periglomerular cells were distinct but they did not show specific morphological characteristics nor a predominant distribution around ND-positive and negative glomeruli. The colocalization study demonstrates that the larger ND and CaBP-stained juxtaglomerular cells, identified according to their size, location and processes branching patterns as two types of short axon cells (superficial short-axon and Van Gehuchten Cells) were also independent populations. PMID- 8439407 TI - Oxidant injury to the alveolar epithelium: biochemical and pharmacologic studies. AB - This multifaceted study involved a combined biochemical and cellular analysis of oxidant metabolism by a lung cell at risk from injury by endogenous and environmental oxidants, the pulmonary alveolar type II epithelial cell. Within the framework of this study, a method was developed for effectively delivering antioxidant enzymes and alpha-tocopherol to the intracellular compartment of alveolar epithelial cells. Alveolar type II cells are key sources of pulmonary surfactant phospholipids and apoproteins and serve as progenitors of type I alveolar epithelium, thus playing an important role in the re-epithelialization of the lung alveolus after exposure to pulmonary oxidants. The type I and II pulmonary epithelium also play an essential collaborative role in maintaining the integrity of the air-blood barrier of the lung. Because of these critical properties of the alveolar epithelium and their recognized sensitivity to oxidant stress derived from diverse sources, such as activated inflammatory cells, hyperoxia, the environmental oxidants and nitrogen dioxide, and surgical procedures, such as cardiopulmonary bypass and lung transplantation, we endeavored to understand more about the oxidant metabolism and antioxidant pharmacology of these cells. In our experiments, we made the observation that loss of differentiated oxidant generation and antioxidant properties of type II cells occurs very rapidly in vitro. For example, we observed a 50% to 75% reduction in the specific activities of type II cell superoxide dismutase, catalase, and glutathione peroxidase, all critical scavengers of cell superoxide and hydrogen peroxide and key enzymes in the attenuation of hydroxyl radical formation. Although the differentiated characteristics of the type II cell antioxidant defenses changed in vitro, they may have become more reflective of type I alveolar epithelial cells. The type I cell is the most vulnerable for oxidant damage in the alveolus because of its large surface area and the possibility of a reduced antioxidant capacity compared to type II alveolar epithelium. In spite of this limitation, we were able to culture type II cells and study their adaptive and toxic responses to exogenously administered oxidant stress. We also observed that a significant source of self-generated oxidants in type II cells was the enzyme xanthine oxidase. Normal rates of oxidant production by this enzyme had an inhibitory effect on incorporation of biosynthetic precursors into surfactant phospholipids; these effects were eliminated by the xanthine oxidase inhibitor, allopurinol.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8439408 TI - Increased production of the TrkB protein tyrosine kinase receptor after brain insults. AB - The protein-tyrosine kinases Trk, TrkB, and TrkC are signal-transducing receptors for a family of neurotrophic factors known as the neurotrophins. Here we show that seizures induced by hippocampal kindling lead to a rapid, transient increase of trkB mRNA and protein in the hippocampus. TrkB is a component of a high affinity receptor for brain-derived neurotrophic factor (BDNF). No change was detected in mRNAs for Trk or TrkC, components of the high affinity nerve growth factor or neurotrophin-3 receptors, respectively. trkB mRNA was also transiently increased in the dentate gyrus following cerebral ischemia and hypoglycemic coma; these treatments had no effect on trk and trkC mRNAs. The increase in trkB mRNA and protein showed the same time course and distribution as the increase in BDNF mRNA. These data suggest that BDNF and its receptor may play a local role within the hippocampus in kindling-associated neural plasticity and in neuronal protection following epileptic, ischemic, and hypoglycemic insults. PMID- 8439409 TI - Both oligodendrocytes and astrocytes develop from progenitors in the subventricular zone of postnatal rat forebrain. AB - The developmental fates of subventricular zone (SVZ) cells of the postnatal rat forebrain were determined by retroviral-mediated gene transfer and immunolabeling for glial antigens. A beta-galactosidase-containing retrovirus injected stereotactically into the SVZ infected small, immature cells. By 28 days post injection labeled cells had appeared in both gray and white matter of the ipsilateral hemisphere. White matter contained labeled oligodendrocytes, but few astrocytes, while neocortex and striatum contained both glial types, often appearing in tightly knit clusters. An analysis after simultaneously injecting alkaline phosphatase- and beta-galactosidase-containing retroviruses showed that cells in each cortical cluster were related. Most clusters contained a single cell type, but approximately 15% contained both astrocytes and oligodendrocytes. These observations strongly suggest that a single SVZ cell can differentiate into both glial types. PMID- 8439410 TI - Localization of TNF alpha and IL-1 alpha immunoreactivities in striatal neurons after surgical injury to the hippocampus. AB - Since the inflammatory process develops after transplantation to the brain, we sought to determine the presence of cytokines following a surgical trauma to the brain of an adult mouse. We report the early and marked presence of tumor necrosis factor-alpha and interleukin-1 alpha in neuronal somata of the striatum following a surgical injury to the hippocampus. The expression of cytokines later extends to neuronal cells of the hippocampus, thalamus, cerebral cortex, brain stem, and cerebellum and to glial cells of the corpus callosum. By contrast, these cytokines are not expressed by neuronal cells following injury to other regions, such as the striatum, cerebellum, and cortex. This study suggests a possible role for certain neurons in the brain's early reaction to a penetrating injury. PMID- 8439411 TI - Cloning and growth of multipotential neural precursors: requirements for proliferation and differentiation. AB - The importance of intrinsic commitments and epigenetic influence to the development of mature neural cell phenotypes was assessed using embryonic day 10 murine neuroepithelial cells, isolated from telencephalon and mesencephalon. Two types of clones were generated with fibroblast growth factor: type-A clones consisted of large, amorphous cells, and type-B clones contained epithelial-like cells. In many type-B clones, very large numbers of precursor cells were produced. Twenty-four percent of type-B clones contained small numbers of neurons, and 59% of clones containing neurons also contained astrocytes, indicating that this clonal type was derived from a bipotential precursor cell. Neuronal differentiation was enhanced by culturing precursor cells with conditioned medium derived from an immortalized astroglial-like cell line. These results indicate that neuroepithelial precursors have discrete epigenetic requirements for their proliferation and differentiation. PMID- 8439412 TI - Developmental switch in the expression of NMDA receptors occurs in vivo and in vitro. AB - The properties of many ligand-gated ion channels are altered during development. We have characterized a developmental switch in the sensitivity of NMDA receptors to the novel antagonist ifenprodil using ligand binding assays with rat brain membranes and voltage-clamp recording of Xenopus oocytes expressing NMDA receptors after injection of RNA from rat brain and from cloned subunits of the receptor. In neonatal rat brain, NMDA receptors have a uniformly high affinity for ifenprodil. During postnatal development, a second population of receptors having a 100-fold lower affinity for ifenprodil is expressed and represents 50% of NMDA receptors in adult rat brain. This developmental change also occurred in cortical neurons maintained in primary culture. Ifenprodil potently inhibited responses of homomeric NR1 and heteromeric NR1/NR2B receptors but not NR1/NR2A receptors expressed in oocytes, suggesting that inclusion of different NR2 subunits in native NMDA receptors can control the sensitivity to ifenprodil. PMID- 8439413 TI - Cell type-specific transcriptional regulation of the Drosophila FMRFamide neuropeptide gene. AB - We have used lacZ reporter gene constructs to study the promoter/enhancer regions of the Drosophila FMRFamide neuropeptide gene in germ line transformants. FMRFamide is normally expressed in approximately 60 diverse neurons of the larval CNS that represent approximately 15 distinct cell types. An 8 kb FMRFamide DNA fragment (including 5 kb of 5' upstream sequence) was sufficient to direct a pattern of lacZ expression that mimicked nearly all spatial aspects of the normal pattern. This result indicates that the cell-specific regulation of FMRFamide expression is largely generated by transcriptional mechanisms. Reporter gene expression was lost from selected cell types when smaller fragments were tested, suggesting that multiple control regions are included in the FMRFamide promoter. One region (a 300 bp fragment from -476 to -162) acted as an enhancer for 1 of the approximately 15 FMRFamide-positive cell types, the OL2 neurons. These results suggest that, in the mature nervous system, the complex pattern of FMRFamide neuropeptide gene expression derives from the activity of discrete, cell type-specific enhancers that are independently regulated. PMID- 8439414 TI - Interaction of synaptotagmin with the cytoplasmic domains of neurexins. AB - Synaptotagmin, a major intrinsic membrane protein of synaptic vesicles that binds Ca2+, was purified from bovine brain and immobilized onto Sepharose 4B. Affinity chromatography of brain membrane proteins on immobilized synaptotagmin revealed binding of alpha- and beta-neurexins to synaptotagmin in a Ca(2+)-independent manner. Using a series of recombinant proteins in which glutathione S-transferase was fused to the cytoplasmic domains of three different neurexins or of control proteins, it was found that synaptotagmin specifically interacts with the cytoplasmic domains of neurexins but not of control proteins. This interaction is dependent on a highly conserved, 40 amino acid sequence that makes up most of the cytoplasmic tails of the neurexins. Our data suggest a direct interaction between the cytoplasmic domains of a plasma membrane protein (the neurexins) and a protein specific for a subcellular organelle (synaptotagmin). Such an interaction could have an important role in the docking and targeting of synaptic vesicles in the nerve terminal. PMID- 8439415 TI - Rings, slings and such things: diagnosis and management with special emphasis on the role of echocardiography. AB - Vascular anomalies of the aorta and pulmonary artery that cause tracheal, esophageal, or tracheoesophageal compression form an important group of congenital cardiovascular malformations. The diagnostic approach to the patient with possible vascular ring is variable. This article presents a systematic approach to the evaluation and management of this fascinating group of malformations, with special emphasis on the role and limitations of echocardiography. Using this approach between September 1990 and March 1992, we identified and defined vascular anomalies of aorta and pulmonary artery in eight children. PMID- 8439416 TI - Echocardiographic recognition of partial papillary muscle rupture. AB - Acute papillary muscle rupture complicating acute myocardial infarction represents a potentially lethal complication of acute myocardial infarction. Survival depends on prompt recognition and institution of immediate medical and surgical therapy. We present two cases of partial papillary muscle rupture in the setting of acute myocardial infarction and describe the echocardiographic features that may allow early recognition of this condition before complete rupture. PMID- 8439417 TI - Transesophageal echocardiographic evaluation of a transthoracic echocardiographic pitfall: a diaphragmatic hernia mimicking a left atrial mass. AB - Diaphragmatic hernia may mimic a left atrial mass when imaged by transthoracic echocardiography. In this case study we emphasize the value of transesophageal echocardiography in clarifying the cause of this apparent atrial mass. PMID- 8439418 TI - Value and limitations of transesophageal echocardiography in the evaluation of aortic prostheses. AB - Results of 34 transesophageal (TEE) studies in patients with suspected aortic prosthetic dysfunction were compared with transthoracic echocardiographic (TTE) results and to anatomic findings. Mass lesions noted at surgery (autopsy) were correctly described in 93% by TEE versus 43% by TTE. Abscesses were detected in 88% by TEE versus 18% by TTE. Bioprosthetic degeneration was visualized in 88% versus 38% and prosthetic obstruction correctly identified in 75% versus 50% by TEE and TTE, respectively. Anatomic aortic regurgitant lesions were identified in 96% by TEE versus 77% by TTE, whereas the correct origin was detected in 88% of cases by TEE versus 54% of cases by TTE. TEE provides valuable additional information on morphologic conditions and flow pathology in aortic valve prostheses. PMID- 8439419 TI - Aortoatrial fistulae diagnosed by transthoracic and transesophageal echocardiography: advantages of the transesophageal approach. AB - Aortoatrial fistulae are uncommon, providing a difficult diagnostic challenge both in the clinical diagnosis and in the choice of an imaging modality that fully delineates the abnormal anatomy and flow patterns. This report describes four cases of aortoatrial fistula resulting from three different underlying causes. The fistula communicated with the right atrium in three cases and the left atrium in one. We also describe the diagnostic information obtained during both transthoracic and transesophageal echocardiography and stress that full detail of the abnormal anatomy and shunting could be obtained only with the transesophageal approach, with its improved image quality of the aortic root. No extra information, other than the coronary anatomy, was obtained during aortography in the two patients who underwent cardiac catheterization. Transesophageal echocardiography should, therefore, be the investigation of choice in patients in whom there is a suspicion of aortoatrial shunting after clinical examination and routine transthoracic studies, and it may avoid the need for invasive investigation in these potentially hemodynamically unstable patients. PMID- 8439420 TI - Atrial lipomatous hypertrophy: lipomatous atrial hypertrophy with significant involvement of the right atrial wall. AB - Lipomatous atrial hypertrophy is a generally benign abnormality characterized by the deposition of adipose tissue in the interatrial septum and is usually detected as an incidental echocardiographic finding. We present two cases in which the presence of lipomatous atrial hypertrophy was diagnosed by transthoracic echocardiography, but tangential cuts of a more diffuse lipomatous process suggested the presence of intracavitary right atrial mass lesions. Transesophageal echocardiography provided additional details of significant right atrial wall involvement. In one case computer assisted tomographic scans showed a progression of thickening over a 4-year period. Lipomatous atrial hypertrophy can be a more generalized and progressive abnormality then previously thought and should be considered in the differential diagnosis of echocardiographic intracavitary right atrial masses. PMID- 8439421 TI - Transgastric imaging: a valuable addition to the assessment of congenital heart disease by transverse plane transesophageal echocardiography. AB - Multiview transgastric imaging was performed with standard single transverse plane transesophageal probes in 16 patients to assess its potential additional value in defining the complexities of congenital heart disease. The age of patients studied ranged from 1.1 to 32 years (mean of 10.4 years). Their body weight ranged from 8.3 kg to 69 kg (mean of 29 kg). In all studies, a complete range of transesophageal and transgastric views could be obtained. The information thus obtained was correlated with the findings of prior precordial echocardiography and subsequent cardiac catheterization or surgical inspection. The pathologic conditions studied included tetralogy of Fallot, (4), isolated ventricular septal defect (4), valvular aortic stenosis (1), subvalvular and valvular aortic stenosis (1), supraaortic stenosis (1), total atrioventricular septal defect (1), secundum atrial septal defect (1), double-outlet right ventricle (1), double-chambered right ventricle (1), and pulmonary atresia, ventricular septal defect, and superoinferior ventricles (1). The single-plane data provided by transgastric scanning were compared and contrasted with that obtained from transesophageal scanning. Transgastric views were shown to be superior to transesophageal imaging in demonstrating the anatomy of the right ventricular outflow tract, the left ventricular outflow tract, and the apical and anterior aspects of the ventricular septum. In addition, these views offered a favorable angle of incidence for spectral wave Doppler studies of flow in both outflow tracts. We conclude that transverse plane transgastric imaging is an important addition to the transesophageal assessment of congenital cardiac disease. Its main additional benefit is in the study of lesions that involve either the right or left ventricular outflow tract or the anteroapical ventricular septum. Its main clinical value is likely to be in the evaluation of the perioperative patient in whom diagnostic precordial imaging is frequently impossible. PMID- 8439422 TI - Noninvasive imaging of intraarterial baffles in infants and children. AB - Baffles within the lumen of the pulmonary artery are created in (1) the Aubert procedure, a variation of the arterial switch favored by some surgeons when two major coronary ostia arise close to one another or when one coronary artery has an intramural course, and (2) the Takeuchi procedure, a technique applied to patients with anomalous origin of the left coronary from the pulmonary artery. In both operations, coronary artery transplantation is avoided; instead, an aorticopulmonary window is created and aortic blood is redirected by an intrapulmonary artery baffle into the coronary circulation. We imaged five patients with Aubert and 10 patients with Takeuchi procedures by use of ultrasound to assess the sequelae of such intraarterial baffles. All five Aubert patients were < 3 weeks old; the ages of the 10 Takeuchi patients ranged from 2 to 86 months. Two patients died early after surgery; the remaining 13 patients were observed for 3 to 83 months (median 46 months). In all 15 patients, the baffle geometry was visualized and the aorticopulmonary window was identified. In the six who had serial imaging, none developed aorticopulmonary window stenosis. In no patient was any peribaffle shunting detected. Supravalvar narrowing, caused by the baffle partially obstructing the neopulmonary artery, was observed in two of five Aubert patients; in only one of these has reoperation been performed. In one of the 10 Takeuchi patients supravalvar narrowing of the pulmonary artery (related to repair of coexistent tetralogy of Fallot) has developed and the patient has since undergone reoperation. PMID- 8439423 TI - In vitro calculation of flow by use of contrast ultrasonography. AB - Contrast echocardiography has been used for qualitative assessment of cardiac function, and its potential for quantitative assessment of blood flow is being explored. With the development of an ultrasound contrast agent capable of passage through the microcirculation, a mathematical model based on classic dye dilution theory, and a digital ultrasound acquisition system, absolute quantitation of myocardial perfusion may be feasible. This study validates the mathematical model in a simple in vitro tube system. Flow was delivered at variable rates through an in vitro tube system while a longitudinal section was imaged with a modified commercial ultrasound scanner. Albunex contrast agent was injected, and videointensity data were captured and analyzed off line. Time-intensity curves were generated, and flow was calculated by use of a mathematical model derived from classic dye dilution mathematics. For 39 different flow rates, ranging for 9.2 to 110 ml/seconds, a correlation coefficient of r = 0.928 (p < 0.001) with a slope of 0.97 was calculated. We conclude that (1) contrast ultrasonography is capable of quantitative determination of flow in an in vitro system, and (2) a mathematical model based on dye dilution theory can be used to calculate flow with accuracy and precision. PMID- 8439424 TI - Accuracy of cardiac output estimation with biplane transesophageal echocardiography. AB - To evaluate the accuracy of cardiac output measurements with biplane transesophageal Doppler echocardiography, we examined 26 sets of observations in 14 patients using thermodilution technique as the standard. A mitral inflow method by single-plane combined the time-velocity integral of mitral inflow at the mitral annulus with the area of mitral annulus, assuming it to be a circular shape, by use of either the four- or the two-chamber view. With both views, a mitral inflow method by biplane combined the average of time-velocity integral of mitral inflow from the four- and the two-chamber views with the area of mitral annulus, assuming it to be an ellipsoid shape. The correlation coefficients between thermodilution and single-plane method of cardiac output were 0.81 (SEE = 0.72 L/min) and 0.85 (SEE = 0.79 L/min) for the four- and the two-chamber views, respectively. The correlation coefficient with biplane method was 0.93 (SEE = 0.47 L/min). Thus, biplane transesophageal Doppler echocardiography can be used for more accurate estimation of cardiac output. PMID- 8439425 TI - Three-dimensional echocardiography: in vitro validation for quantitative measurement of total and "infarct" surface area. AB - The rapid development of numerous therapeutic options for myocardial revascularization requires more advanced, quantitative echocardiographic methods such as measurement of total endocardial and infarct surface area to evaluate myocardial infarction and assess the effects of therapy. Two-dimensional echocardiography is insufficiently quantitative for this purpose because it cannot directly measure three-dimensional relationships with such as volume and surface area. To limitation this limitation we have developed a three-dimensional echocardiograph capable of measuring total and regional or "infarct" surface area. In vitro validation of this method has been carried out comparing computed areas with true areas of a pin model and fixed hearts. Infarcts were demarcated on the fixed hearts by placing pins in the myocardium. The pin heads on the epicardial surface defined infarct regions that could be imaged. True surface areas of the pin model were determined by physical measurement and calculation. True areas of the fixed hearts were determined by planimetry of surface casts made with plastic tape. Accuracies for total and infarct areas were 1.36% and 2.13% for the pin model and 1.61% and 3.48% for the fixed hearts. Interobserver variability for both phantoms was less than 2.5%. The standard error of the estimate predicting total and infarct surface area for the fixed hearts was 1.53 cm2 and 0.71 cm2, respectively (p < 0.001). Three-dimensional echocardiography provides a new, accurate method for directly measuring global and regional surface areas and holds promise for improved evaluation of myocardial infarction and assessment of its treatment. PMID- 8439426 TI - Academic physicians' opinions on preliminary reporting of echocardiographic data. AB - Preliminary reporting of echocardiographic data by cardiac sonographers has become a key issue in the echocardiography community. A survey on this issue was sent to 248 academic physicians and 89 (35.8%) were returned. In response to a question in the survey, 76 physicians stated that they had at least a limited amount of knowledge in echocardiography. For the group, 62% wanted a written or verbal preliminary report and 52% concluded that this report should be a part of the cardiac sonographer's position. If cardiac abnormalities are suspected, 65% wanted the results before the cardiologist reviewed the study, but only 42% of the physicians wanted a diagnostic versus a descriptive type of report. About 49% stated that if necessary they would attempt to influence the cardiac sonographer to give them a preliminary report, whereas 67% of the physicians would possibly use this information to medically manage the patient. Fifty percent believed that it was legal for a cardiac sonographer to give a preliminary report. Another 70% said that the cardiac sonographer would NOT be "practicing medicine without a license" and 66% concluded that they would NOT be "aiding and abetting the unauthorized practice of medicine" if given this information. These data have important potential ramifications for both cardiac sonographers as well as for the practice of cardiology regarding the issue of preliminary echocardiographic reports. PMID- 8439427 TI - Transesophageal echocardiography in the detection and surgical management of a papillary fibroelastoma of the mitral valve causing partial mitral valve obstruction. AB - Primary mitral valve tumors are rare. We describe the transesophageal appearances of a papillary fibroelastoma (Lambl's giant excrescence) of the anterior mitral valve leaflet causing partial mitral valve obstruction. Transesophageal echocardiography proved particularly useful in identifying the limited attachment of the tumor to the anterior mitral valve leaflet and excluding its attachment to the interatrial septum. These features helped to exclude the possibility of the tumor being a left atrial myxoma, the primary differential diagnosis of the lesion. Transesophageal echocardiography enabled the planned surgical option to be mitral valve repair and also allowed intraoperative monitoring to assess the results of the surgical repair. PMID- 8439428 TI - Double cardiomyopathy: coexistent cardiac amyloidosis and hypertrophic obstructive cardiomyopathy. AB - A combination of hypertrophic obstructive cardiomyopathy (HOCM) and cardiac amyloidosis in the same patient is very rare. Clinical diagnosis could be extremely difficult and may require myocardial biopsy. We are reporting a patient with this combination who was referred to our institution because of features of HOCM based on clinical, echocardiographic and Doppler criteria. Cardiac amyloidosis was only recognized after myocardial biopsy that failed to reveal evidence of HOCM. Only after the patient expired from severe, intractable heart failure did the autopsy findings confirm the association of HOCM. We believe that the combination of the two cardiomyopathic processes is very rare and makes treatment extremely difficult. PMID- 8439429 TI - Partial thrombosis of a bileaflet mitral prosthetic valve: diagnosis by transesophageal echocardiography. AB - We describe the contribution of transesophageal echocardiography in the diagnosis of acute thrombosis of a bileaflet mechanical prosthetic valve in the mitral position. The thrombus had immobilized one hemidisc without affecting the function of the other. These findings were confirmed at surgery. PMID- 8439430 TI - The transesophageal echocardiographic features of double-orifice left atrioventricular valve. AB - Three adult patients with a double-orifice left atrioventricular valve (AV) were studied by both precordial and transesophageal ultrasound imaging, (two transverse plane and one biplane studies) to compare and contrast the information obtained by either imaging modality. In two patients, this pathologic condition was associated with other congenital heart malformations--a muscular inlet ventricular septal defect in the first, atrioventricular and ventriculoarterial discordance and an unrestrictive ventricular septal defect in the second. In the third patient, the double-orifice left AV valve existed as an isolated lesion. In the first and second case, both orifices were of similar size; in the third the additional orifice was of diminutive size and was demonstrated only by transesophageal longitudinal plane scanning. In summary, in this adult patient group, transesophageal echocardiography with color flow mapping was superior to precordial scanning in the assessment of both the morphology and functional status of a double-orifice left AV. PMID- 8439431 TI - Knowledge of AIDS and other sexually transmitted diseases among women attending a family planning clinic in Nairobi, Kenya. AB - We interviewed 1,716 women attending a family planning clinic in Nairobi between January 1990 and May 1991 about their knowledge of the acquired immunodeficiency syndrome (AIDS) and other sexually transmitted diseases (STDs). When participants in the study were asked to name spontaneously the STDs they knew, more than 90% of the women named gonorrhea and AIDS, and 75.0% named syphilis; 65.4% could name two or more signs of AIDS; and 96.9%, 66.5%, and 58.3% mentioned sexual transmission, transmission via blood transfusion, and perinatal transmission, respectively, as routes of transmission of AIDS. Knowledge of most symptoms and routes of transmission of AIDS, as well as knowledge of gonorrhea and syphilis, was significantly positively associated with level of education. Unmarried women were significantly less likely to know symptoms and routes of transmission of AIDS than were married women. Level of knowledge of gonorrhea and syphilis was significantly positively associated with number of lifetime sexual partners. Although awareness of AIDS was very high, detailed knowledge of signs of AIDS and routes of transmission was deficient, particularly among less educated women. This positive association of detailed AIDS knowledge with level of education suggests a need to design AIDS prevention activities that are more accessible to, and better understood by, women who have little education. PMID- 8439432 TI - AIDS knowledge in minorities: significance of locus of control. AB - A convenience sample of 587 subjects from the community health centers of Harris County, Texas, completed a structured interview that included questions on knowledge of AIDS transmission and prevention and on the Wallston Health Locus of Control (HLOC) Scale. HLOC score was a strong independent predictor of AIDS knowledge, with high externality associated with less knowledge. In a regression equation predicting AIDS knowledge, HLOC contributed 3% of the variance after education and ethnicity were accounted for. Hispanic and black individuals had a higher external orientation than white individuals. These findings suggest the need to address personal beliefs and perceptions concerning risk and to consider HLOC when educating patients and the public about AIDS. PMID- 8439433 TI - Evaluation of two AIDS prevention interventions for inner-city adolescent and young adult women. AB - Two hundred and fourteen young women received acquired immunodeficiency syndrome (AIDS) prevention interventions at an inner-city family health center serving minority patients predominantly. The community in which the health center is located has a high incidence of intravenous (IV) drug abuse. Either a peer or a health care provider delivered the intervention. In the peer-delivered intervention, a trained peer educator reviewed with patients an AIDS "Rap" videotape and several AIDS brochures, which imparted information about human immunodeficiency virus (HIV), its transmission, and prevention. In the provider delivered intervention, family practice residents, attending physicians, and nurse practitioners used a patient-centered counseling approach to convey the same information. Questionnaires administered immediately before and after the intervention and at one month follow-up evaluated changes in knowledge, attitudes, and behavior. Analyses of data from both combined intervention groups revealed significant improvements in several areas of knowledge, including the effectiveness of using a condom and cleaning IV drug implements with bleach to prevent transmission of HIV. Many improvements were retained at the one-month follow-up. In addition, subjects in both groups who were sexually active stated immediately after the intervention that asking a sexual partner about past sexual experience would now be less difficult, and at one-month follow-up they reported a significant decrease in the frequency of vaginal sex. Our findings suggest that counseling by physicians can achieve more changes in knowledge of sexual risks, whereas peer education can achieve greater changes in knowledge about IV drug use. Results show that both approaches to AIDS prevention used in this study can significantly affect knowledge, attitudes, and sexual behavior. PMID- 8439434 TI - Cigarette smoking and lens opacities: the Beaver Dam Eye Study. AB - We evaluated the relationship between cigarette smoking behavior and lens opacities in cross-sectional data on 4,926 adults in Beaver Dam, Wisconsin. The frequencies of more severe levels of nuclear sclerosis increased with packyears of cigarette smoking in women and men. For women, the odds ratio (OR) associated with 10 packyears was 1.09 (confidence interval [CI] = 1.04, 1.16) and for men it was 1.09 (CI = 1.05, 1.14) after controlling for age. The frequencies of posterior subcapsular opacities also increased in both sexes with increased packyears. The OR associated with 10 packyears of cigarette smoking was 1.06 (CI = 0.98, 1.14) for women and 1.05 (CI = 1.00, 1.11) for men after controlling for age. There was no significant effect on cortical opacities. Smoking was associated with past cataract surgery. The significant relationships of smoking with lens opacities suggest an etiologic effect. If confirmed prospectively, our results would indicate another benefit of smoking cessation. PMID- 8439435 TI - Pharmacological approaches to smoking cessation. AB - Currently, 28% of U.S. adults smoke, and this percentage is declining by 0.5% per year; however, this rate of decline must double if the goal in Healthy People 2000 (smoking prevalence of no more than 15% among adults) is to be reached. To help decrease physiological barriers to smoking cessation, numerous pharmacological approaches have been used. I review the effectiveness of these approaches, including interventions reported in the relatively older literature as well as more recent approaches, such as nicotine replacement, clonidine, antianxiety agents, and antidepressants. I also discuss the results and design of clinical trials. PMID- 8439436 TI - Body composition and blood pressure in children based on age, race, and sex. AB - We evaluated 675 nine- and twelve-year-old children for body composition and circulatory differences based on age, race, and sex. The specific variables measured included height, weight, triceps and subscapula skinfolds, body mass index, percentage fat, fat-free weight, and systolic, diastolic, and mean arterial blood pressures. A 2 x 2 x 2 factorial multiple analysis of variance (MANOVA) test of significance showed body composition and blood pressure differences (P < .01) for race, age, and sex. The univariate test of the specific variables within the factors showed that black children had higher fat-free weights and lower fat levels but higher blood pressure values (P < .05) than white children. Boys had lower fat levels than girls, and the older children had higher values on the body composition variables but not on blood pressure. Zero order correlations between body composition and blood pressure ranged from 0.14 to 0.55; systolic blood pressure and body weight shared the highest correlation. These data show that, although black children have less body fat than white children, they are heavier and have higher blood pressure. We hypothesize that some aspect of fat-free body weight may contribute to hypertension in black individuals. PMID- 8439438 TI - Evaluation of a method for detecting outbreaks of diseases in six states. AB - A new statistical method, developed for detection of changes in reporting, has proved useful in analysis of provisional data reported by state health departments to the National Notifiable Diseases Surveillance System (NNDSS). In this system, data from the current four-week period can be compared with data from the previous, same, and subsequent four-week periods from each of the preceding five years, and reports exceeding historical limits are highlighted in a horizontal bar graph. To evaluate the usefulness of this method at the state level, we applied it to weekly reports of seven notifiable diseases in six states over a four-month period. Participating state health departments investigated all events exceeding historical limits and reported known outbreaks that were not identified by the method. During the four-month period, the method identified 27 episodes of disease reports exceeding historical limits. Of these, 14 (52%) represented outbreaks. None was detectable by analysis of aggregate national surveillance data. Five outbreaks known to state health department officials were not identified by the method, because of increased disease activity during the baseline period or lack of timely provisional reporting of outbreak-related cases. Methods for detection of increases in reporting at the state level may identify events of public health importance that are obscured in aggregate national data and may supplement other local sources of information available to state health departments in the recognition of significant public health events. PMID- 8439437 TI - The current practices of internists in prevention of residential fire injury. AB - Residential fires are a leading cause of unintentional injury in the United States. We completed a cross-sectional study in an urban internal medicine clinic to describe the patients' risk factors for fire injury and internists' current methods for addressing this health problem. We used a physician self-report survey (n = 301), patient interviews (n = 300), and chart reviews (n = 300) in the evaluation. Among physicians returning the questionnaire (70% response rate), more than 85% demonstrated reasonable knowledge of injury as a major health problem and relatively positive attitudes toward incorporating injury prevention into clinical practice. However, 62% of physicians reported "never" and 23% only "seldom" counseling patients about smoke detectors. Among patients attending the clinic, only 63% reported having a smoke detector in their home. Factors associated with not having a smoke detector through multivariate logistic analysis were black race (odds ratio [OR] = 4.3, confidence interval [CI] = 1.7, 10.6) and patient report that physician did not counsel about smoke detectors (OR = 2.38, Cl = 1.15, 4.90). Age younger than 65 (OR = 1.7, Cl = .93, 2.9) and alcohol abuse (OR 1.5, Cl = .92, 2.5) were borderline in their statistical significance. Eighteen percent of the patients reported being counseled by their physician about smoke detectors, although no documentation appeared in any of the charts. In addition, those patients with risk factors for fire injury did not report being counseled more often than their lower risk counterparts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8439439 TI - Sensitivity and specificity of self-examination for cutaneous malignant melanoma risk factors. AB - We wanted to determine whether self-examination for skin pigmentary characteristics associated with cutaneous malignant melanoma might help identify persons at high risk for this cancer. Dermatology patients without melanoma were asked to record the number of freckles on the right forearm, number of palpable arm nevi, and nevi greater than five millimeters in diameter on the entire body (factors that have been associated with increased risk for malignant melanoma). Each participant was independently examined for the same features in a standardized clinical exam. With the exam as the standard, we determined sensitivities and specificities for each of these characteristics at several different cutpoints. Specificity ranged from 83% to more than 95% for these three cutaneous markers. Sensitivity was 88% or higher for freckling status, 63% for detecting one or more palpable arm nevus, and 68% for detecting large nevi. These results indicate that self-exam may be useful in identifying individuals at high risk for melanoma. PMID- 8439440 TI - The effect of routine use of computer-generated preventive reminders in a clinical practice. AB - Computer-generated reminders for patients and physicians can increase provision of preventive services. On July 1, 1989, the Department of Family Medicine at the Medical University of South Carolina extended a computerized prevention reminder system to all physicians and adult patients in the department's clinical practice. The prevention program consisted of computer-generated physician reminders for any deficiencies in five preventive services at the time of patient visits, a personalized patient reminder letter sent just before a patient's birthday, and educational interventions. We defined adherence using a population based approach, that is, the percentage of all eligible patients who had received the preventive services within the recommended period of time. The data revealed that the percentage of patients who received preventive services either increased or remained stable during the 12-month study period, which ended July 1, 1990. Adherence was greater for women, for older patients, and for those with Medicare/Medicaid and HMO insurance. We noted higher rates of adherence for all five preventive services, compared with baseline rates of adherence recorded on July 1, 1988. A population-based approach to prevention allows physicians to become more active in providing preventive care to patients. Computer-based reminder and tracking systems can integrate population-based prevention into practice. PMID- 8439441 TI - How much do health care providers know about AIDS? AB - We sent a survey to more than 8,000 New Jersey health professionals to collect information on their knowledge level, attitudes, and prevention practices relating to the human immunodeficiency virus (HIV) and the acquired immunodeficiency syndrome (AIDS). The surveys were distributed through the mail in three separate waves with a postcard reminder. A total of 2,725 individuals provided completed questionnaires (34% response rate). We assessed the AIDS and HIV-related knowledge level of these health professionals, compared their knowledge levels, and identified variables that predict a high level of knowledge. The overall test scores indicate a definite need for AIDS education among these health professionals; on average, doctors answered 71% of the knowledge items correctly; dentists, 66%; and nurses, 65%. Doctors scored higher than the other health professionals on almost all of the 38 items relating to the epidemiological aspects of HIV, transmission, identification and reporting of HIV disease and AIDS, and assessment of HIV-associated risks. The multivariate regression model explained 24% of the variability in knowledge score (P = .0001) and identified the following independent variables as significant predictors of knowledge score: age, race, marital status, religious beliefs, political orientation, professional group, average number of hours worked each week, experience with HIV+/AIDS patients, knowledge self-assessment, and sources of AIDS information. PMID- 8439442 TI - Validity, reliability, and generalizability in studies of AIDS knowledge, attitudes, and behavioral risks based on subject self-report. PMID- 8439443 TI - Cigarette smoking and cataract. PMID- 8439444 TI - Molecular basis of heritable connective tissue disease. AB - The family of collagens represents a series of highly vulnerable gene-protein systems. This can be explained by the fact that both the folding of the pro alpha chains and the assembly of collagen monomers into fibrils highly depend on the principle of nucleated growth, in which every subunit of the system must have the correct structure. DNA analysis showed that over 90% of patients with OI have mutations in one of the two structural genes for type I procollagen, that many patients with severe chondrodysplasias apparently have mutations in the gene for type II procollagen, and that most patients with the potentially lethal type IV variant of Ehlers-Danlos syndrome have mutations in the gene for type III procollagen. The incidence of such genetic diseases varies from 1:100,000 births for lethal forms of OI to 1:25,000 births for mild forms (48). Mild chondrodysplasias such as the Stickler syndrome may have an incidence of 1:10,000 births. It is the subject of current investigation whether some mutations in the genes for type I, II, and III procollagen can also cause some of the common diseases of later onset, such as osteoporosis, osteoarthritis, or familial aneurysms. These genes have been demonstrated to be mutated in at least some subsets, and further analysis of the exceptionally large genes for most collagens is underway to resolve these questions. Rapid DNA analysis techniques, which are developed independently in several laboratories and in a concerted effort through the human genome project, will soon make it possible to screen a population for genetic defects and identify people at risk for developing connective tissue disease. As vulnerable as the collagen gene-protein system might be, the multimeric collagens may prove nevertheless to be accessible to gene therapy, as the suppression of defective alleles, e.g., through antisense strategies, may be much easier to accomplish than the gene augmentation necessary to correct other genetically determined diseases. PMID- 8439445 TI - Expression of recombinant human glutathione reductase in eukaryotic cells after DNA-mediated gene transfer. AB - Glutathione reductase (EC 1.6.4.2) protects tissues from oxidant stress by catalyzing the NADPH-mediated reduction of glutathione disulfide to glutathione. We describe construction of a vector for DNA-mediated gene transfer and successful transient overexpression of human glutathione reductase cDNA in CHO cells. No expression was observed when the same vector was transiently transfected into NIH3T3 or LA4 cells or stably integrated in CHO cells. These results demonstrate the ability to constitute recombinant glutathione reductase expression in eukaryotic cells but suggest that this expression may be toxic. PMID- 8439446 TI - Decrease in the NAD level in tumor-derived cultured fibroblasts from neurofibromatosis patients. PMID- 8439447 TI - 13-cis-retinoic acid affects oxidation and DNA damage in oxidative-positive SLE lymphocytes but may not be useful for therapy. AB - 13-cis-Retinoic acid (13-CRA), a water-soluble vitamin A analog and 5' lipoxygenase inhibitor, was tested in vitro for effects on excess oxidative metabolism and DNA damage in mitogen-stimulated lymphocytes from patients with systemic lupus erythematosus (SLE), because other 5'-lipoxygenase enzyme inhibitors were shown to lower the excess oxidative metabolism in SLE cells. Excess chemiluminescence (CL) was abolished within minutes after the addition of 1 x 10(-6) M 13-CRA in five of five CL-positive mitogen-stimulated SLE lymphocytes, and was lowered in five of eight samples after 48 to 72 h culture. Similarly, low concentrations of 13-CRA for 48-72 h largely prevented the S1 nuclease-sensitive DNA changes/DNA damage observed in CL-positive lupus lymphocytes in vitro. However, 13-CRA did not affect DNA damage in four of four CL-negative lymphocyte samples. 13-CRA, like other retinoic acid compounds, was known to stimulate B-cell activities in vivo and in vitro but effects on dividing lupus T cells had not been studied. 13-CRA further inhibited the diminished PHA stimulated lupus T-cell growth in tissue culture at a concentration of 9 x 10(-6) M in three of five lupus lymphocyte samples. 13-CRA has positive and negative effects on multiple aspects of the immune system and it is not clear whether 13 CRA will have positive or adverse clinical effects on SLE patients. Close attention to vitamin A and vitamin "supplements" in patients with SLE may answer this question. PMID- 8439448 TI - Fatty acid composition and the oxidation of low-density lipoproteins. AB - The effect of the fatty acid composition of low-density lipoprotein (LDL) on copper-ion-catalyzed oxidation of isolated LDL was examined in 18 normolipidemic men. The decrease in LDL linoleic acid concentration (delta L) during oxidation was found to be strongly correlated with initial LDL linoleic acid concentration (r = 0.976, n = 18, P < 0.001), whereas the production of thiobarbituric acid reacting substances (TBARS) was not. The concentration of oleic acid in LDL was then increased significantly (mean increase 20%, P < 0.05) in 8 male volunteers by a daily dietary supplement of rapeseed oil/muesli for 4 weeks. The mean delay before copper-ion-catalyzed production of conjugated dienes (the lag phase) was significantly (P < 0.001) greater in LDL isolated after the study period (67 min) than that of before the study period (40 min). The rate of formation of conjugated dienes, delta L and TBARS production during oxidation of LDL was not significantly altered by the rapeseed oil/muesli supplement. These results suggest that the linoleic acid content of LDL is a determinant of individual variability in LDL oxidation, and that a rapeseed oil/muesli dietary supplement reduces the susceptibility of LDL to oxidation. PMID- 8439449 TI - Factors that influence radioimmunoassay of human plasma melatonin: a modified column procedure to eliminate interference. AB - We describe here the effect of various agents and conditions that can influence the assay of plasma melatonin and report a modified column method which minimizes these interferences. Melatonin was measured by a sensitive radioimmunoassay which can detect melatonin from 5 to 500 pg/ml; the assay was linear about 0-60 pg/ml range. The hemolysis of samples increases the apparent level of melatonin in plasma. When the hemolyzed samples were passed through the SEP-cartridge and washed with methanol, the normal basal level was restored. Elution from the column was highest at 100% methanol and proportionate with the "spiked" value of melatonin. The addition of hemoglobin standard and serum albumin decreases the assayed value of melatonin while the addition of red blood cells and heparin increases the level. EDTA, oxalate, and citrate do not influence the basal level of melatonin. Samples that have been affected by these various agents and conditions can be normalized by passing samples through the column. Up to three cycles of freezing and quick thawing of plasma had no effect on the assay of melatonin; however, beyond three cycles levels were reduced. Long-term storage (up to 4 years) has no influence on the assay. PMID- 8439450 TI - Effect of urease-induced hyperammonemia on metabolism of guanidino compounds. AB - We previously reported that guanidino compounds produced by the catabolism of arginine play an important role in the pathophysiology of acute hyperammonemia. In order to understand the metabolism of guanidino compounds during sustained hyperammonemia, we investigated the effect of intraperitoneal urease injection (800 IU/kg) on the levels of guanidino compounds in blood, liver, kidney, and brain of rats. Control rats received an equal volume of saline. Eight hours following injection, rats were sacrificed and blood and tissues were removed. Ammonia and urea were determined by enzymatic and colorimetric assays, respectively. Guanidino compounds were analyzed by high-performance liquid chromatography. Blood and tissue ammonia were significantly increased and urea decreased in urease-treated animals. Blood and kidney arginine levels were significantly decreased although hepatic arginine was increased following urease injection. Elevated hepatic arginine may be due to the rapid conversion of urea to ammonia by urease and the development of a futile urea cycle. Catabolites produced by the transamidination of arginine were significantly decreased in the blood, liver, kidney, and brain of urease-treated rats, whereas acetylation of hepatic arginine to alpha-N-acetylarginine was increased. Blood and tissue guanidinosuccinic acid levels were not elevated during urease induced hyperammonemia, supporting the hypothesis that urea is a precursor for the synthesis of guanidinosuccinic acid. PMID- 8439451 TI - Regulation of liver glycogen synthesis from [14C]glucose and [14C]lactate by portal-arterial glucose difference in the perfused rat liver. AB - To study effects of the portal-arterial glucose difference on the hepatic glycogenesis, the liver was isolated from fasted rats and was bivascularly perfused. Thirty-five milliliters of Krebs-Ringer buffer (pH 7.4) with 2 mM glucose, 3 mM lactate, 20 ng/ml insulin, and [1-14C]glucose or [U-14C]lactate was recirculated at flow rates of 14 ml/min via the portal vein and 7 ml/min via the hepatic artery. Glucose was continuously infused at a rate of 27.75 mumol/min into the portal (P experiment) and the arterial cannula (A experiment), and the portal-arterial glucose gradients were +1.98 and -3.96 mM. Perfusate glucose concentration was not different between the P and A experiments within 20 min. Perfusate lactate level was higher in the P experiment than in the A experiment at 20 min. Incorporation of radioactivity from [14C]glucose into glycogen was higher in the P experiment than in the A experiment (0.245 +/- 0.014%/20 min vs 0.175 +/- 0.022%/20 min, P < 0.01), and not influenced by the addition of insulin. Incorporation of 14C from [14C]lactate into glycogen was not different between the P and A experiments, and was significantly increased with the addition of insulin. This activity, in the presence of insulin, was higher in the P experiment than in the A experiment (0.490 +/- 0.028%/20 min vs 0.406 +/- 0.025%/20 min, P < 0.05). These results suggest that the portal-arterial glucose difference has an important role in the regulation of hepatic glycogenesis from exogenous glucose and gluconeogenesis. PMID- 8439452 TI - Increased plasma apolipoprotein E-rich high-density lipoprotein and its effect on serum high-density lipoprotein cholesterol determination in patients with familial hyperalphalipoproteinemia due to cholesteryl ester transfer activity deficiency. AB - Plasma apo E-rich HDL was studied in regard to its quantity and chemical composition in the members of a family with cholesteryl ester transfer activity deficiency, exhibiting familial hyperalphalipoproteinemia. The approach involved a simple precipitation method established in our laboratory. Serum apo E-rich HDL concentrations for two homozygous members were elevated up to 66 and 60 mg/dl in terms of cholesterol (normal, 6.7 +/- 2.3 mg/dl, n = 38), and to 9.4 and 10.8 mg/dl in terms of apo E (normal, 2.6 +/- 1.5 mg/dl, n = 38). The cholesterol/apo E ratio (mole/mole) of apo E-rich HDL was higher in two homozygotes (669 and 531) than in two cholestatic patients with elevated apo E-rich HDL (268 and 149) and in normal subjects (242 +/- 115, n = 38). Chromatographic studies of the serum from a homozygote showed enlargement of all HDL subclasses and apo E in the larger HDL subclass. These facts indicate that the increase of apo E-rich HDL in this disease occurs secondarily to the enlargement of HDL particles, which require substances to cover their cores, having expanded due to the accumulation of cholesteryl ester. The sera from the homozygotes gave HDL cholesterol concentrations which were remarkably discrepant among commercial precipitating reagents, because of the difference in recovery of apo E-rich HDL with these reagents. PMID- 8439453 TI - Clinical and biochemical studies in an American child with sialuria. AB - Sialuria is a rare inborn error of sialic acid (NeuAc) metabolism resulting from failure of CMP-NeuAc to adequately feedback inhibit the rate-limiting enzyme in sialic acid synthesis, UDP N-acetylglucosamine (UDP-GlcNAc) 2-epimerase. We describe the fourth reported sialuria patient, T.W., whose clinical features include developmental delay, coarse facies, and massive urinary excretion of sialic acid. Biochemical studies of T.W. fibroblasts revealed a 200-fold increase in free NeuAc content compared with normal. Bound NeuAc was only slightly elevated. The free NeuAc was predominantly in the cytosol fraction of fibroblasts after differential centrifugation, with only 4% of the free NeuAc content in other (nuclear, granular, and microsomal) cellular compartments. CMP-NeuAc inhibited UDP-GlcNAc 2-epimerase by 80% in normal fibroblasts but inhibited the epimerase of T.W. (sialuria) cells by only 13%. Cytidine feeding of sialuria fibroblasts decreased the intracellular free NeuAc content by 47%; this was accompanied by a fourfold increase in CMP-NeuAc, which may be sufficient to feedback inhibit the mutant epimerase and reduce free NeuAc production. Cytoplasmic pH was determined by the pH sensitive fluorescent indicator 2',7' bis(carboxyethyl)-5(6)-carboxyfluorescein, pentaacetoxymethylester (BCECF/AM) using the H+ equilibration method. The intracellular pH of sialuria fibroblasts, 7.18 +/- 0.04, was not found to be significantly different from that of normal cells (7.19 +/- 0.08). PMID- 8439454 TI - Type 1 Gaucher disease: molecular, biochemical, and clinical characterization of patients from northern Portugal. AB - We report the study of 16 catholic type 1 Gaucher disease patients originating from a well-defined region in the north of Portugal where a relatively high incidence is observed. The patients were screened for mutations: 3060G-->A, 5841A ->G, 5976C-->G, and 6433T-->C, which enabled the identification of 27 of the 32 mutated alleles. Four different genotypes were identified, namely 5841G/6433C (n = 6), 5841G/5841G (n = 5), 5841G/? (n = 4), and 6433C/? (n = 1). All but one of the patients carried at least one 5841G mutated allele, making its frequency 62.5%, which is similar to that described for Ashkenazi Jewish patients. The 5841G homozygotes presented an overall milder clinical profile, whereas no clear genotype/phenotype correlation could be established for heterozygous patients. On the basis of residual glucocerebrosidase activity, no distinction could be made between 5841G homozygotes and 5841G/6433C compound heterozygotes. Patients that had at least one 5841G allele (encoding the Ser 370 mutated enzyme) all presented a cell-type-specific residual glucocerebrosidase activity as well as an increased molecular activity when measured in the presence of the physiological activators. PMID- 8439455 TI - [A better adolescence]. PMID- 8439456 TI - [Burns: better safe than ...]. PMID- 8439457 TI - [Relatives--a resource in home care nursing]. PMID- 8439459 TI - [A clinical eye]. PMID- 8439458 TI - [Pediatric clinics]. PMID- 8439460 TI - ["New spring" in long-term psychiatry? To change an old post]. PMID- 8439461 TI - [Preventive health activities. The role of occupational health services]. PMID- 8439462 TI - [Preventive health activities. Why does health personnel need occupational health services?]. PMID- 8439463 TI - [Children in hospital--before and after]. PMID- 8439464 TI - Medicare outpatient payment reform--Part 2. PMID- 8439465 TI - More on the role of cytoreductive surgery for ovarian cancer. PMID- 8439466 TI - Impact of mammography media campaign assessed at 4 years. PMID- 8439467 TI - Helping low-income minority women reduce cancer risk. PMID- 8439468 TI - Clinical trials referral resource. Clinical trials with topotecan. PMID- 8439469 TI - Radioimmunoguided surgery for colorectal cancer. AB - This article provides a basic understanding of the RIGS (radioimmunoguided surgery) technique and reviews the evolution of the technology from its inception as an experimental technique in animal models to the current clinical trials in patients. A review of published data from the laboratory and from preclinical and clinical trials is updated by a statement of the current status of RIGS. A look at the future of RIGS as an experimental and clinical tool highlights current areas of investigation based on this technology. PMID- 8439470 TI - Male-female differences in the impact of cancer therapy. AB - Sex has been shown to be a significant predictor of cancer survival, with females living longer than males. This survival differential could occur because women benefit more than men from cancer treatments. This article reports the results of a study of the adequacy of the current clinical trials literature to examine sex differences in response to cancer therapy. All phase III (randomized) trials of cancers in non-sex-specific sites published between 1988 and 1990 were identified in three cancer-specific and four general medical journals. Of 55 studies that investigated outcomes by sex, 33% reported differences. Future studies should include adequate numbers of male and female participants, where appropriate, to allow generalization of study findings; routine reporting of the sex composition of the study sample in clinical trials reports; and routine analysis of the effects of sex on prognosis and responses to specific treatments. PMID- 8439472 TI - Anti-neutrophil cytoplasmic antibody-associated glomerulonephritis in children. AB - Two cases of anti-neutrophil cytoplasmic antibody (ANCA)-associated necrotizing and crescentic glomerulonephritis are reported. A 12-year-old girl and a 10-year old boy presented with polyarthritis, anaemia, haematuria, proteinuria, impaired renal function, anorexia, nausea, marked loss of weight and lethargy. The boy also had a vasculitic rash and anterior uveitis. Both children had diffuse cytoplasmic ANCA identified by indirect immunofluorescence and confirmed by specific enzyme-linked immunosorbent assay. Renal biopsies showed severe focal and segmental necrotizing glomerulonephritis with 100% crescents. They were treated with plasma exchange, prednisolone, cyclophosphamide and heparin. Within 1 month of commencing treatment, both had normal serum creatinine concentrations and ANCA was not detectable. Renal biopsies 6 weeks following commencement of treatment revealed quiescent disease, although up to 40% of glomeruli were sclerosed or had fibrous crescents. Following cessation of cyclophosphamide and heparin after 7 months and reduction in steroid dose, a biopsy at 10 months in the boy revealed quiescent disease, but the girl had recurrent disease associated with reappearance of a low titre of ANCA and small cellular crescents in 20% of the glomeruli. These cases reflect the potential usefulness of ANCA determination for categorizing paediatric patients, helping in the selection of therapy and as a possible marker of disease activity, similar to the experience in adults. PMID- 8439471 TI - Gout, uric acid and purine metabolism in paediatric nephrology. AB - Although gout and hyperuricaemia are usually thought of as conditions of indulgent male middle age, in addition to the well-known uricosuria of the newborn, there is much of importance for the paediatric nephrologist in this field. Children and infants may present chronically with stones or acutely with renal failure from crystal nephropathy, as a result of inherited deficiencies of the purine salvage enzymes hypoxanthine-guanine phosphoribosyltransferase (HPRT) and adenine phosphoribosyltransferase (APRT) or of the catabolic enzyme xanthine dehydrogenase (XDH). Genetic purine overproduction in phosphoribosylpyrophosphate synthetase superactivity, or secondary to glycogen storage disease, can also present in infancy with renal complications. Children with APRT deficiency may be difficult to distinguish from those with HPRT deficiency because the insoluble product excreted, 2,8-dihydroxyadenine (2,8-DHA), is chemically very similar to uric acid. Moreover, because of the high uric acid clearance prior to puberty, hyperuricosuria rather than hyperuricaemia may provide the only clue to purine overproduction in childhood. Hyperuricaemic renal failure may be seen also in treated childhood leukaemia and lymphoma, and iatrogenic xanthine nephropathy is a potential complication of allopurinol therapy in these conditions. The latter is also an under-recognised complication of treatment in the Lesch-Nyhan syndrome or partial HPRT deficiency. The possibility of renal complications in these three situations is enhanced by infection, the use of uricosuric antibiotics and dehydration consequent upon fever, vomiting or diarrhoea. Disorders of urate transport in the renal tubule may also present in childhood. A kindred with X linked hereditary nephrolithiasis, renal urate wasting and renal failure has been identified, but in general, the various rare types of net tubular wasting of urate into the urine are recessive and relatively benign, being found incidentally or presenting as colic from crystalluria. However, the opposite condition of a dominantly inherited increase in net urate reabsorption is far from benign, presenting as familial renal failure, with hyperuricaemia either preceding renal dysfunction or disproportionate to it. Paediatricians need to be aware of the lower plasma urate concentrations in children compared with adults when assessing plasma urate concentrations in childhood and infancy, so that early hyperuricosuria is not missed. This is of importance because most of the conditions mentioned above can be treated successfully using carefully controlled doses of allopurinol or means to render urate more soluble in the urine. Xanthine and 2,8-DHA are extremely insoluble at any pH. Whilst 2,8-DHA formation can also be controlled by allopurinol, alkali is contraindicated. A high fluid, low purine intake is the only possible therapy for XDH deficiency. PMID- 8439473 TI - Clinical quiz. Sweat test indicates cystic fibrosis in a child with sweat sodium of 99 mmol/l and sweat chloride of 139 mmol/l. PMID- 8439474 TI - Glomerular morphometry in reflux nephropathy: functional and radiological correlations. AB - Using computerized digitometry, we investigated the relationships between renal size, glomerular filtration rate (GFR), proteinuria, incidence of segmental and global glomerulosclerosis, glomerular size, hilar arteriolar wall thickness and hyaline deposition in renal biopsies obtained from 24 children and adolescents with reflux nephropathy, of whom only 4 were hypertensive. Age-matched controls comprised minimal-change nephrotic syndrome (6) and recurrent haematuria with normal biopsy (13). The mean sectional area of patients' glomeruli was double that of controls. Glomerular size correlated with the amount of proteinuria (measured as protein/creatinine ratios in early morning urine) and inversely with renal size and GFR. Segmental sclerosis, invariably of hilar origin, was observed in 8 patients and the percentage of glomeruli affected correlated strongly with glomerular size and proteinuria. Global sclerosis was found equally in patients and controls, and showed no similar correlations. Compared with controls, patients' hilar arterioles showed increased wall thickness, more intramural hyaline deposits and decreased luminal diameter when related to glomerular size. The proteinuria and glomerular changes are consistent with hyperfiltration, while the previously undescribed hilar vascular changes, which both precede and accompany sclerosis, resemble abnormalities reported experimentally following renal ablation. PMID- 8439475 TI - Reversible tubular proteinuria precedes microalbuminuria and correlates with the metabolic status in diabetic children. AB - Early tubular alterations were studied in 53 children with insulin-dependent diabetes mellitus (IDDM), 32 of whom were followed at regular 6-monthly intervals for 3 years. The urinary levels of retinol-binding protein (RBP), beta 2 microglobulin and brush border antigens (BBA) (determined by monoclonal enzyme immunoassay) were taken as indices of functional and cellular tubular alterations; urinary albumin was considered an early marker of glomerular alterations. All indices of tubular alterations were higher in IDDM children than in 368 normal children, while albuminuria was unchanged. Urinary levels of BBA, however, varied widely during follow-up, with 25 of the 32 IDDM patients who were followed at regular intervals having pathological values for BBA on at least one occasion, followed by normalization. Metabolic alteration was found to be the main cause of this variability, since a high statistical correlation was found between urinary BBA and fructosamine (P < 0.001) and between RBP and the stable fraction of glycosylated haemoglobin (P < 0.001). The data confirm that transient tubular proteinuria occurs in diabetic children before any other marker of renal involvement such as microalbuminuria. The maintenance of good metabolic control is essential to normalize this early abnormality that can be considered a reversible sign of functional renal involvement. PMID- 8439476 TI - Glomerular lesions in adolescents with gross hematuria or the nephrotic syndrome. Report of the Southwest Pediatric Nephrology Study Group. AB - We report clinical and pathological data in 56 adolescents presenting with gross hematuria (GH) and 65 presenting with idiopathic nephrotic syndrome (INS). IgA nephropathy (present in 52%) and other mesangial lesions were found in the majority of the 56 patients with GH. Many of these patients had complex urological procedures prior to consideration of a nephrological problem. This often led to significant delays in making the appropriate diagnosis. Pathological lesions in the 65 patients with INS included minimal change NS (MCNS) in 31%, membranous glomerulonephritis (MGN) and focal segmental glomerulosclerosis (FSGS) in 18.5% each, and membranoproliferative GN (MPGN) in 12%. In 47 of the patients with INS, in whom no specific treatment had been given prior to renal biopsy, MCNS and MGN were observed with a similar frequency (26% and 23%, respectively), with FSGS and MPGN being found in 21% and 11%. These results indicate that the pathological lesions in adolescents with INS who undergo a renal biopsy more closely resemble those in adults, and are usually more severe than those in young children. However, it should be noted that our study was retrospective. Hence, there were probably some adolescents with INS who had a successful response to therapy and therefore did not have a renal biopsy performed. PMID- 8439477 TI - Renal artery stenosis secondary to neurofibromatosis in children: detection by Doppler ultrasound. AB - Renal artery stenosis was diagnosed in two adolescents with neurofibromatosis using Doppler ultrasound. The diagnosis was confirmed by angiography. The renal vascular lesion in neurofibromatosis usually affects the proximal segment of the artery, which is the part most optimally visualized by ultrasound. We suggest that Doppler ultrasound of the renal arteries may be a useful technique in the investigation of hypertensive children with neurofibromatosis. PMID- 8439478 TI - Salt-deficient diet and early weaning inhibit DNA synthesis in immature rat proximal tubular cells. AB - A maturational gradient exists between the inner and the outer cortical nephrons in infant rats. This study compares the putative growth-retarding effects of early weaning (EW) and a salt-deficient (SD) diet in proximal tubule (PT) cells in the inner and the outer cortex. The mitotic response was measured as tritiated thymidine incorporation in PT cells from 18- to 22-day-old rats. Under basal conditions the mitotic index is the same in the inner and the outer cortex. EW retarded body growth, but had no significant effect on the kidney/body weight (KW/BW) ratio. EW caused a significant decrease in DNA synthesis in both the outer and the inner cortical PT cells, but the effect was significantly more pronounced in the outer cortex. The SD rats had significantly lower levels of serum sodium, lower urinary sodium excretion, slightly decreased BW, but no differences in KW/BW ratio or in dry/wet KW. SD caused a decrease in DNA synthesis in the PT cells in the outer cortex, but not in the inner cortex. In conclusion, two manipulations that can retard proliferation of PT cells, i.e. EW and a SD diet, have a more pronounced effect in immature than in mature PT cells. PMID- 8439479 TI - Recurrent nephrotic syndrome after transplantation: early treatment with plasmaphaeresis and cyclophosphamide. AB - Steroid-resistant nephrotic syndrome (NS) with focal glomerulosclerosis (FGS) and its recurrence after transplantation are mainly seen in children. The recurrence rate approximates 30% and the graft loss is about half this. Several therapeutic regimens have been proposed, giving conflicting results. In an attempt to remove a putative circulating factor and inhibit its production by lymphocytes, three patients with biopsy-proven FGS in the native kidney were included in a prospective uncontrolled trial using early plasmaphaeresis followed by substitutive immunoglobulins in association with methylprednisolone pulses and cyclophosphamide instead of azathioprine over a 2-month period. The patients were girls, aged 6.5, 13.3 and 15.8 years, who received a cadaveric transplant; concomitant immunosuppression included prednisone and cyclosporine A. All three patients exhibited early recurrence of the NS and were treated 5-10 days after the onset of proteinuria. Rapid and sustained remission was achieved in all patients within 12-24 days on therapy. One patient experienced a late acute but steroid-sensitive rejection episode; another suffered from septic ankle arthritis as a complication of reinforced immunosuppression. The latter girl had a second late recurrence of proteinuria that was controlled within 7 weeks. With a 18- to 27-month follow-up, all three patients have normal renal function, normal blood pressure and no proteinuria. We conclude that intensive therapy using plasmaphaeresis, steroid pulses and cyclophosphamide over a 2-month period can induce complete remission in children with early recurrence of NS after transplantation. PMID- 8439481 TI - Pharmacokinetics of recombinant human erythropoietin applied subcutaneously to children with chronic renal failure. AB - The single-dose pharmacokinetics of recombinant human erythropoietin (rHuEPO) given SC was investigated in 20 patients aged 7-20 years at different stages of chronic renal failure. In a pilot study we confirmed the lower bioavailability of the drug in 2 children when given SC compared with the IV route (24% and 43%, respectively). Following administration of 4,000 units/m2, rHuEPO SC effective serum erythropoietin concentrations increased from a mean baseline level (+/- SD) of 23 +/- 13 units/l to a mean peak concentration of 265 +/- 123 units/l, which was reached after 14.3 +/- 9.4 h, followed by a slow decline until baseline values were attained at 72 h. Mean residence time was 30 +/- 9 h and mean elimination half-time 14.3 +/- 7 h. The single-dose kinetics of SC rHuEPO in children with different degrees of renal failure are comparable to those in adult patients. Possibly, the higher efficacy of SC rHuEPO in patients with renal anaemia compared with IV rHuEPO is related to its prolonged action. PMID- 8439480 TI - Glomerular injury in end-stage liver disease--role of circulating IgG and IgM immune complexes. AB - The relationship of IgG- and IgM-bound circulating immune complexes and immune dysfunction to glomerular injury was evaluated in 15 children with end-stage liver disease (ESLD) awaiting liver transplantation. Compared with age-matched controls, children with ESLD had significantly (P < 0.01) increased serum IgG, IgA, and IgM levels, as well as IgG- and IgM-bound circulating immune complexes. Furthermore, they showed a significant (P < 0.05) depression of C3 and C4 levels compared with controls. Hematuria occurred in 66% of children with ESLD, and the urinary protein/creatinine ratio was also significantly (P < 0.01) increased compared with controls (4.65 +/- 2.56 vs. 0.16 +/- 0.04 mg/mg). Light microscopy of renal biopsy tissue obtained from 6 children with ESLD at the time of transplantation demonstrated mesangial proliferation and expansion with basement membrane splitting. This was associated with subendothelial deposits on electron microscopic examination, compatible with a diagnosis of membranoproliferative glomerulonephritis. By immunofluorescence, deposition of IgG, IgA, and IgM occurred in various combinations with co-deposition of complement fragments. We conclude that membranoproliferative glomerulonephritis is a common finding in children with ESLD, probably due to entrapment of circulating IgG- and IgM-bound immune complexes. PMID- 8439482 TI - Fatal pulmonary haemorrhage and crescentic glomerulonephritis without autoantibodies: a paediatric case report. AB - The case of an 8-year-old girl who had a fatal pulmonary haemorrhage and crescentic glomerulonephritis without autoantibodies is presented. Circulating anti-glomerular basement membrane antibodies, circulating immune complexes and anti-neutrophil cytoplasmic autoantibodies were not detected. To our knowledge this is the youngest reported case of the disease. PMID- 8439483 TI - Long-term follow-up of a patient with Gitelman's syndrome. AB - The long-term follow-up (from age 6 to 20 years) of a girl with Gitelman's syndrome, who had four hypomagnesaemic-tetanic episodes associated with normal plasma calcium, hypokalemia and hypocalciuria, is presented. During and after puberty, hypomagnesaemia was of the order of 0.41-0.49 mmol/l and plasma potassium was at the lower reference limit. The long-term clinical course and growth of this patient appeared good, but, magnesium supplementation reduces the risk of tetanic crises. PMID- 8439484 TI - Hypoproteinemia in the hemolytic-uremic syndrome of childhood. AB - A retrospective review of admission serum protein concentration in 18 children with hemolytic-uremic syndrome (HUS) showed significantly decreased serum total protein, albumin and globulin concentrations upon admission compared with 22 matched controls (P < 0.003). One child with atypical disease without diarrhea had normal serum protein concentrations. A strongly positive correlation (P = 0.006) was found between the age of HUS patients with diarrhea and their lowest total protein concentrations. In 10 children who eventually required hemodialysis, there was a significantly negative correlation (r = -0.8316, P = 0.01) between the admission serum albumin and the patients' highest creatinine levels, suggesting that hypoproteinemia may be a risk factor in the development of renal failure. The pathophysiological and clinical significance of hypoproteinemia in HUS needs further investigation. PMID- 8439485 TI - Intracranial calcifications associated with nephrogenic diabetes insipidus. AB - A 6-year-old boy with nephrogenic diabetes insipidus (NDI) and intracranial calcification is reported. The calcifications were symmetrical and located in the basal ganglia and in the subcortical regions of the frontal, temporal, parietal and occipital lobes. Episodes of hyperosmolality during infancy are considered to be one of the causes of intracranial calcification in NDI. However, other unknown factors may be involved, because up to now there have been no reports of intracranial calcification in patients with central diabetes insipidus. PMID- 8439486 TI - Assessment of urine specific gravity by reagent strip test in newborn infants. AB - Specific gravity was measured with a strip test (N-Labstix SG, Ames Division, Miles, Puteaux, France) in 98 urine specimens obtained from 57 newborn infants; osmolality was measured with an osmometer. The strip test did not accurately predict urine osmolalities; a very weak correlation was found between the specific gravity and the osmolality (r2 = 0.598, P < 0.01). Specific gravity values up to 1.015 always indicated hypotonic urine with osmolality less than 211 mosmol/kg H2O, whereas higher values could be associated with either hypotonic or hypertonic urine. Therefore, the strip test cannot be recommended in the neonatal period because its clinical usefulness is strictly restricted to urine samples with low specific gravities (< or = 1.015) and without confounding variables (urine pH > or = 6.5, glucosuria, proteinuria, haematuria). PMID- 8439487 TI - Congenital nephrosis in association with hypothyroidism and hypoadrenocorticism. AB - Adrenal abnormalities are rarely recognized in association with the nephrotic syndrome. This report describes the hospital course of an 11-week-old child with congenital nephrotic syndrome secondary to diffuse mesangial sclerosis, in addition to hypothyroidism and hypoadrenocorticism. PMID- 8439488 TI - Tubulointerstitial nephritis in methylmalonic acidemia. AB - We report two patients with methylmalonic acidemia (MMA) in whom renal biopsy demonstrated interstitial nephritis, bringing the total of such reported cases to four. In addition, hypertension, observed in one of our patients, has not been previously reported as the presentation of renal disease in MMA. The etiology of interstitial nephritis in MMA did not appear to be due to urate nephropathy. To date, 15 patients with MMA have been reported with renal complications, including chronic renal failure, making it imperative that children with MMA have their renal status evaluated. PMID- 8439489 TI - Familial hypouricaemia due to an isolated tubular defect of urate reabsorption. AB - Hypouricaemia due to an isolated renal tubular defect is a rare condition. Several members from an affected family are described. The propositus is a 12 year-old girl with hypouricaemia (0.7-1.1 mg/dl) and increased fractional excretion of uric acid (50%). Pyrazinamide and sulphinpyrazone tests revealed an attenuated response in this subject to both drugs. The mother and one of the propositus' two brothers have the same defect. The other brother has uric acid levels at the lower limit of normal and increased fractional excretion of uric acid. These results suggest familial hypouricaemia due to a pre-secretory reabsorptive tubular defect, transmitted by autosomal dominant inheritance. PMID- 8439490 TI - Immunotactoid glomerulopathy in a child with Down syndrome. AB - A 9-year-old girl with Down (21-trisomy) syndrome was found to have proteinuria and microscopic haematuria at age 6 years. Proteinuria gradually increased during the next 3 years, although blood pressure and renal function remained normal. The patient exhibited no underlying systemic diseases, monoclonal gammopathy, cryoglobulinaemia or histological evidence of plasmacytoma. A percutaneous renal biopsy revealed immunotactoid glomerulopathy (fibrillary glomerulonephritis) characterized by thickening of the glomerular basement membrane, diffuse mesangial expansion and various-sized acid-Schiff-positive nodules that were intensely positive for IgG, light chains (kappa and lambda) and complement components (C3, C4, C1q) along the glomerular capillaries in the mesangium. Congo red dye and amyloid thioflavine T staining were negative. Fibrils (15-17 nm in diameter--larger than amyloid fibrils) were present in the mesangial area and within the glomerular basement membrane. We are not aware of a previous report of immunotactoid glomerulopathy and a patient with chromosomal abnormalities. PMID- 8439491 TI - Non-immunological risk factors in paediatric renal transplantation. AB - In paediatric renal transplantation, non-immunological risk factors account for about one-third of graft losses. Recurrence of original disease is observed mainly in primary hyperoxaluria and glomerulopathies such as steroid-resistant nephrotic syndrome and membranoproliferative glomerulonephritis. In both glomerulopathies, 20% of grafts are lost from recurrence. Vascular thrombosis is, in most series, the second cause of graft loss in children, particularly in young recipients or with young donors (under 5 years of age). Non-compliance with treatment is a common non-immunological factor in adolescent recipients, which may trigger a severe rejection process resulting in graft loss. The role of factors related to graft preservation and intra- and post-operative management (ischaemia time, delayed graft function) or to cytomegalovirus infection is less obvious in our series. Prevention of vascular thrombosis and of non-compliance is most important in order to improve the results of paediatric renal transplantation. PMID- 8439492 TI - Regulation of cell function by extracellular matrix. AB - The extracellular matrix (ECM) provides structural support and adhesive substrates for the body tissues. Recent advances in our understanding of the biology of matrix indicate that the ECM also plays a significant role in regulating the behavior of cells. Matrix proteins engender changes in cell shape and movement, bind growth factors, and facilitate cell-cell and cell-matrix interactions. Matrix-induced differentiation results from multiple stimuli that include: tensile forces on the cell, cytokine- or growth factor-mediated stimulation, and interaction with bioactive domains of matrix glycoproteins. Because these signals are important determinants of cell behavior, pharmacological manipulation of cell-matrix interactions may offer a valuable new approach to disease treatment. PMID- 8439493 TI - Stem cell origins of leukaemia and curability. AB - It is suggested that most childhood acute lymphoblastic leukaemias and some other paediatric cancers are chemo-curable because they arise in stem cell populations that are functionally transient, chemosensitive and programmed for apoptosis. Most adult acute leukaemias are chemo-incurable at least in part because they originate in relatively drug resistant stem cells with extensive self-renewal capacity. The latter property in turn increases the probability of clones evolving with multi-drug resistance. Particular mutations may superimpose additional adverse features on leukaemic cells. PMID- 8439494 TI - Garlic and its significance for the prevention of cancer in humans: a critical view. AB - Recently published results of epidemiologic case-control studies in China and Italy on gastric carcinoma in relation to diet suggest that consuming garlic may reduce the risk of gastric cancer. Chemical constituents of garlic have been tested for their inhibiting effect on carcinogenesis, using in vitro and in vivo models. In most experiments inhibition of tumour growth was established using fresh garlic extract, garlic compounds or synthetically prepared analogs. In this review the strengths and weaknesses of the experiments are discussed and the outcomes are evaluated to assess the possible significance of garlic or garlic compounds for the prevention of cancer in humans. It is concluded that evidence from laboratory experiments and epidemiologic studies is presently not conclusive as to the preventive activity of garlic. However, the available evidence warrants further research into the possible role of garlic in the prevention of cancer in humans. PMID- 8439495 TI - Characterisation of a humanised bispecific monoclonal antibody for cancer therapy. AB - A humanised bispecific monoclonal antibody (bsMAb) with binding specificity for carcinoembryonic antigen (CEA) on one arm and a radiolabelled chelate (DTPA-90Y) on the other arm was generated by consecutively transfecting the humanised genes of an anti-CEA MAb and the chimerised genes of an anti-chelate MAb into eucaryotic BHK cells using the calcium-phosphate coprecipitation technique. The antibodies secreted were of IgG3 isotype with a shortened hinge region (delta gamma 3) and light chains. Double transfectomas were screened for the secretion of bsMAbs using a double determinant enzyme-linked immunosorbent assay (ELISA) based on solid phase attached HSA-benzyl-DTPA and an anti-idiotypic MAb selective for the CEA-specific arm. After purification on two immunoaffinity chromatography columns, the humanised bsMAbs were characterised by SDS-PAGE and a quantitative binding assay in antigen excess. The purification procedure resulted in 95% reactive bispecific MAb. This humanised bsMAb may be employed in two phase radioimmunotherapy, binding to the tumour via the anti-CEA arm and localising a radiolabelled chelate with the other arm, without inducing a strong immune response observed sometimes with murine MAbs. PMID- 8439496 TI - Tumour growth inhibition in mice by glycosylated recombinant human lymphotoxin: analysis of tumour-regional mononuclear cells involved with its action. AB - We compared the antitumour effects of glycosylated LT (gLT), nonglycosylated LT and TNF against a solid tumour in mice. We found that: (a) The systemic administration of gLT showed significant antitumour activity. These effects were, however, quite small in nude mice. Nonglycosylated LT and TNF attained the same degree of effectiveness as gLT, but at a 5-times higher dose. The serum half-life of gLT was 3-fold longer than that of nonglycosylated LT and 22-fold longer than that of TNF. (b) The effect of gLT was significantly blocked by pretreatment with anti-asialo GM1 antibody. Treatment with gLT produced a significant reduction in numbers of tumour-regional mononuclear cells, which in turn, produced increases intensive necrosis. (c) Mononuclear cells in the tumour tissues before gLT injection were predominantly IL-2 receptor +/CD3- cells and CD3+ cells. Pretreatment with the anti-asialo GM1 antibody produced a drastic reduction of IL 2 receptor +/CD3- cells. These findings suggest that the efficient antitumour effect of gLT is due to a longer serum half-life than that of nonglycosylated LT or TNF in vivo, and its function is largely mediated by IL-2 receptor +/CD3- cells. PMID- 8439497 TI - Carcinoembryonic antigen: enhancement of liver colonisation through retention of human colorectal carcinoma cells. AB - Carcinoembryonic antigen (CEA) is an oncofetal antigen whose function in the progression of colorectal carcinoma remains unclear although recent studies suggest it participates in homotypic cellular adhesion. We have previously shown that 40 micrograms of CEA injected intravenously into athymic nude mice enhances experimental metastasis in liver and lung by two human colorectal carcinoma cell lines that are injected intrasplenically 30 min later. The metastatic potential of another three moderately to highly metastatic colorectal carcinoma cell lines and of one weakly metastatic line has now been analysed in this model. CEA pretreatment only enhanced colony formation by cell lines that were weakly metastatic in untreated nude mice; it did not affect experimental metastasis by highly metastatic lines. CEA pretreatment enhanced the retention of 125I Idudr labelled weakly metastatic tumour cells within the liver and lungs 4 h after intrasplenic injection but not the retention of highly metastatic tumour cells or inert latex beads. A significant correlation existed between the formation of experimental metastases and the early retention of tumour cells within the liver after intrasplenic injection. Aggregation did not appear to be important for retention in liver because CEA did not aggregate colorectal carcinoma cells in vitro. Also CEA did not alter natural host effector cell function in a cytolysis assay in vitro. We suggest that CEA facilitates liver colonisation by three of eight human colorectal carcinomas in athymic nude mice by increasing the hepatic retention of tumour cells. The potential mechanisms by which CEA may increase the retention of tumour cells in the liver are discussed. PMID- 8439498 TI - Cytophotometric DNA content and argyrophilic nucleolar organiser regions of oesophageal carcinoma. AB - The cytophotometric DNA content and the argyrophilic nucleolar organiser regions (AgNORs) of biopsy specimens taken before undergoing any treatment were examined in 91 surgically treated oesophageal carcinoma cases. There was a significant linear dependence between the mean DNA content and the number of AgNOR per nucleus (AgNOR number) (r = 0.615, P < 0.001). The DNA distribution pattern and the range of the AgNOR number also showed a significant correlation (P < 0.01). Twenty three of 28 cases with a low AgNOR number (< 4) were then determined to have a diploid pattern (type II), while 17 out of 22 cases with a high AgNOR number (> or = 6) had high ploidy values (type IV). The patients with a type II DNA distribution pattern and a low AgNOR number thus showed a good post-operative course with a 5 year survival rate of 55.2%, whereas no patients survived over 4 years among the 17 cases with both a type IV DNA pattern and a high AgNOR number (P < 0.001). These data thus demonstrate the close relationship between cytophotometric DNA content and AgNOR number and suggest that the combined detection of these two parameters, using biopsy specimens, should be of benefit in making an accurate preoperative evaluation of prognosis for patients with oesophageal carcinoma. PMID- 8439499 TI - Different HSP70 expression and cell survival during adaptive responses of 3T3 and transformed 3T3 cells to osmotic stress. AB - Responses both to hyperosmotic stress and to heat shock were compared in 3T3 cells, spontaneously transformed cells (ST3T3) and simian virus 40-transformed cells (SV3T3). Cell adaptation to these stresses was measured in terms of surviving cell viability and plating efficiency, while their induced synthesis of stress proteins was monitored in terms of the presence of mRNA for HSP70, the pattern of polypeptides synthesised and the accumulation of HSP70 detectable by monoclonal antibodies. All three types of cells responded similarly to heat shock in their expression of HSP70 and showed no clear differences in ability to recover. In contrast, both ST3T3 and SV3T3 cells adapted more poorly and much more slowly to hyperosmotic stress (0.5 osM incubation) than did normal 3T3 cells. This different pattern of adaptation to hyperosmotic stress was parallelled by the cells' different expression of a stress protein that could not be distinguished from the heat-induced HSP70 by any of the methods listed above. In view of these findings it seems possible that hyperosmotic treatment might be useful in selectively affecting the survival of tumour cells. PMID- 8439500 TI - Epithelial cell proliferation in the sigmoid colon of patients with adenomatous polyps increases during oral calcium supplementation. AB - To study the effect of oral supplemental calcium on colonic epithelial proliferation, 17 adenomatous polyp patients received 1.5 g Ca2+ as calcium carbonate daily during 12 weeks, while on a calcium constant diet, based on the patients' habitual diet. Seven subsequently continued calcium supplementation for 9 months without dietary restrictions. Epithelial proliferation rate in colonic biopsies, expressed as labelling index (%), was determined with 5 bromodeoxyuridine and immunohistochemistry. Biopsies were taken from the midsigmoid at time of polyp excision and at the end of the intervention period. Median labelling index increased from 6.1% before to 8.7% after 12 weeks calcium (n = 17, P < 0.02). This was due to increased labelling in the basal third of the crypts (11.9 vs 16%), whereas labelling in mid and luminal compartments was not affected. Labelling index remained increased after 1 year calcium supplementation at 8.8%. Crypt length was not affected by calcium. These results are in contrast to those of others, who have shown a decrease of rectal epithelial proliferation during similar doses of calcium. Therefore, the effect of nutritional intervention on colonic epithelial proliferation should be studied in biopsies taken not only from the rectum, but also from more proximal parts of the colon. Caution with respect to large scale intervention studies with calcium in high risk groups is mandatory. PMID- 8439501 TI - Neuroblastoma in a transgenic mouse carrying a metallothionein/ret fusion gene. AB - We have recently succeeded in producing transgenic mice carrying a hybrid gene consisting of mouse metallothionein promoter-enhancer and the ret oncogene (MT/ret). (Iwamoto et al., 1991b). A retroperitoneal tumour developed in one of 17 MT/ret transgenic founder mice. Histological analysis revealed that the tumour consisted of undifferentiated neuroblasts and differentiated ganglion cells, the latter of which were strongly positive for neuron specific enolase. Expression of the ret transgene was observed at high levels in RNA from the tumour, but not in those of other normal tissues. In addition, a 100kDa ret protein was detected in the cell lysate of the tumour. Taken together with our previous data, these results suggest a possible role for the ret oncogene in the proliferation of neural crest cells. PMID- 8439502 TI - Temporal sequence and cellular origin of interleukin-2 stimulated cytokine gene expression. AB - A study of activation of the cytokine network by interleukin 2, IL-2, may provide a rationale for devising cytokine combination and cytokine antagonist treatments with increased anti-tumour efficacy and decreased toxicity. We have investigated the expression of mRNA for 13 cytokines and three transcription factors during in vitro culture of peripheral blood mononuclear cells, PBMC, with IL-2. A consistent pattern of induction was seen in nine individuals, with early (2-24 h) induction of IL-1 beta, IL-6, tumour necrosis factor, TNF, lymphotoxin, LT, and gro. TNF and LT mRNA was expressed continually throughout culture, but levels of mRNA for IL-1 beta, IL-6, and gro declined by 24-48 h. After 48 h, PBMC began to express mRNA for IFN-gamma, IL-5, GM-CSF, and M-CSF. At 15 min to 1 h post IL-2 mRNA for c-fos, c-jun, and c-myc, and TNF was induced in three individuals studied. IL-4, IFN-alpha, and IL-1 alpha mRNA was not detected. Only a minority of cells expressed mRNA for TNF, IL-1 beta, IL-6 and IFN-gamma, and monocytes were the main source. Levels of cytokine protein in culture supernatants mirrored the pattern of mRNA induction. This in vitro model shows clear parallels with the reported in vivo production of cytokines during IL-2 therapy, and may prove useful in designing new therapeutic strategies. PMID- 8439503 TI - Transforming growth factor-beta 1 as a signal for induction of cell death by apoptosis. AB - Cell death by apoptosis is a major determinant of growth of normal tissues and tumours. The present study aimed to elucidate signal factors involved in its regulation. Epithelial cells in control liver, during regression of cyproterone acetate induced liver hyperplasia, in liver (pre)neoplasia and in uterus undergoing apoptosis in vivo show immunostaining for transforming growth factor beta 1 (TGF-beta 1) as detected by anti-pre(266-278) TGF-beta 1 antibodies. Positive immunostaining is also seen in a few intact cells of hyperplastic, regressing liver apparently preparing for apoptosis, but is virtually not found in hepatocytes of normal or growing liver nor in cells undergoing death by necrosis. Recombinant latency associated protein (rLAP, dimer of the pro-region non-covalently associated with the mature region) complex and mature TGF-beta 1 induce apoptosis in isolated hepatocytes cultured in vitro. These findings suggest an involvement of TGF-beta 1 in the induction of apoptosis in certain epithelia in vivo. PMID- 8439504 TI - Effective treatment of malignant hypercalcaemia with a single intravenous infusion of clodronate. AB - Thirty patients with hypercalcaemia due to malignancy that persisted following rehydration, were treated with a single dose of the bisphosphonate, clodronate. Clodronate (1.5 g) was administered intravenously in 500 ml normal saline over 4 h. Serum and urine biochemistry were measured before and after treatment and the results were compared with data from 15 patients given the recommended regimen 300 mg intravenous clodronate daily for 5 consecutive days. The single infusion induced a rapid and significant fall in serum calcium, apparent at day 3 (P < 0.0001) that persisted to the end of follow-up at day 10 (P < 0.001). Eighty per cent (24/30) of patients became normocalcaemic. The response was associated with a significant decrease in fasting urinary calcium excretion, and no change in renal function, as judged by serum creatinine. The same dose of clodronate, given as 5 daily infusions, induced a comparable decrease in serum calcium, but was less rapid in onset so that at day 3 the serum calcium was significantly lower with the single infusion (P = 0.02). The calcium lowering effect of both regimens depended on the tumour type. We conclude that the single infusion of 1500 mg clodronate is as effective in reducing serum calcium as the same dose given over 5 days. The single infusion has a more rapid onset of effect, is more convenient than multiple infusions, and has no adverse effect on renal function. PMID- 8439505 TI - Dynamic test with recombinant interferon-alpha-2b: effect on 90K and other tumour associated antigens in cancer patients without evidence of disease. AB - We have previously shown that a short course of recombinant interferon-alpha-2b (rIFN-alpha-2b) (3 million units day for 5 days) for patients with primary gynaecologic malignancies was able to increase the circulating levels of a newly discovered tumour associated antigen, termed 90K. In this study, we have investigated the effects of the same modality of administration of rIFN-alpha-2b in 62 patients with breast and colorectal cancer whose primary tumour was surgically removed 1 month before and who were without evidence of disease (NED) at the time of the study. A significant increase of 90K serum concentration was already observed 24 h after the first r-IFN-alpha-2b injection and persisted throughout the investigational period. The increase was more pronounced in patients with a basal 90K-negative than a 90K-positive assay. Of 54 patients who started the test with a 90K negative assay, 17 (31%) shifted to a positive assay after rIFN-alpha-2b. Twenty-eight of 62 (45%) patients exhibited a 90K value above the mean increment of the whole population. The serum levels of CEA, CA-15 3, CA 19-9, and alpha-fetoprotein measured in the same serum samples were not modified. After 2 years of follow-up, ten patients relapsed. Six of them showed a 90K increase above the mean increment of the whole population. As with ovarian cancer, the increase of 90K following r-IFN-alpha-2b administration might be of importance for the early detection of disease recurrence in clinically NED breast and colon cancer patients. PMID- 8439506 TI - Clinical profile and problems of management of 108 cases of germ cell tumours of testis at Institute Rotary Cancer Hospital, All India Institute of Medical Sciences New Delhi 1985-1990. AB - A retrospective analysis of 108 cases of primary germ cell tumours of testis seen over a 6 year period at Institute Rotary Cancer Hospital of All India Institute of Medical Sciences, New Delhi is presented. There were 45 (42%) cases of seminoma and 63 (48%) of non-seminomatous germ cell tumours (NSGCT). The median age at presentation was 35 and 30 years respectively. Almost half (56) patients presented in advanced stage (stages IIc-IV). Tumours in undescended testis formed an important subgroup (14%). The standard approach of treatment was radiotherapy in stages I & II seminomas and chemotherapy in bulky seminomas and metastatic NSGCT. Chemotherapy protocols used were VAB-6 and PVB. Although a policy of surveillance has been practised for stage I NSGCT, it is debatable whether it is universally suitable for our patients. The results of treatment in low volume disease are comparable to that in the west but the management of bulky disease requires a more aggressive approach. Unfortunately only 74 out of 108 (68.5%) patients were able to complete the treatment prescribed. Most of the defaulters were from the chemotherapy group because of inability to afford the drugs. The probability of survival of those who completed treatment was 0.77 at 4 years. Since testicular tumours are largely curable, a more vigorous policy of detection, follow up and treatment needs to be pursued. Better screening of children with undescended testis will reduce cancer in this group. Failure to provide chemotherapy to all patients is particularly unfortunate for a curable disease like testis cancer. PMID- 8439508 TI - Cytological reporting of cervical abnormalities according to endocervical status. AB - An analysis of cytology reporting within Victorian Cytology Service demonstrates that the proportion of Papanicolaou smears which were reported as including an endocervical component increased from approximately one half during 1987-89 to more than three quarters during 1990-91. The improvement coincided with the routine provision of special sampling instruments to all practitioners supplemented by an education program. Despite the increase in endocervical sampling, no increase in the rate of reporting of high-grade intraepithelial lesions of the cervix has occurred. An increase between the two time periods in the cytological reporting of adenocarcinoma, adenocarcinoma in situ and endocervical dyskaryosis has occurred, but does not reach statistical significance. PMID- 8439507 TI - Reduced expression of TGF beta is associated with advanced disease in transitional cell carcinoma. AB - The gene structure and expression of the related peptide regulatory factors TGF beta 1 and TGF beta 2 were studied in a panel of seven urothelial carcinoma cell lines and 40 transitional cell carcinomas. The latter comprised 15 grade 1, 18 grade 2 and 5 grade 3 tumours and two cases of carcinoma in situ. Control tissues included ten matched 'field' biopsies and 17 other biopsies including 11 biopsies of macroscopically normal urothelium, two of which were from patients with no history of bladder cancer. No amplification of rearrangements of either TGF beta 1 or TGF beta 2 were detected in any sample. A complex pattern of expression or the two genes was found in the urothelial cell lines. High, but variable levels of the 2.5 kb TGF beta 1 transcript were detected and lower and more variable levels of the three (4.1 kb, 5.1 kb and 6.5 kb) transcripts of TGF beta 2 were detected. Although those cell lines expressing most TGF beta 1 tended to express less TGF beta 2 transcript there was no clear-cut relationship. In comparison, no TGF beta 2 transcript was identified in any primary transitional cell carcinoma or control tissue. Markedly reduced or undetectable levels of TGF beta 1 transcript were detected in 4/15 (26%) grade 1, 5/18 (28%) grade 2 and 3/5 (60%) grade 3 tumours. There was no clear relationship to tumour stage, lymphocytic infiltration or stromal content of the tumours. Clinical review one year after the 2 year period of tumour collection showed that 6/9 (66%) of patients with tumours with reduced levels of transcript had died or had disease which was not controllable by local resection and 3/9 (33%) had developed tumour re occurrences. In comparison, in the group with normal levels of expression of TGF beta 1, 3/18 (17%) had disease which was not controllable by local means, 9/18 (50%) had tumour re-occurrence and 6/18 (33%) had no evidence of disease. The association of reduced expression of TGF beta 1 and advanced disease was statistically significant P < 0.02 (Fisher's test). Although the sample size is small, we suggest that the loss of expression of TGF beta 1 may be a potential marker of progressive disease or prognosis in transitional cell carcinoma and warrants further study. PMID- 8439509 TI - Gastric cancer with p53 overexpression has high potential for metastasising to lymph nodes. AB - Overexpression of the tumour suppressor gene p53 was investigated immunohistochemically in 96 primary gastric carcinomas and 26 corresponding metastatic perigastric lymph nodes. Abnormalities in p53 expression were found in 52 (54%) of the 96 primary carcinomas. Tumours stained positively for p53 frequently metastasised to lymph nodes (the metastatic rate: 85%) compared to findings in those with negative p53 staining (64%, P < 0.05). Ninety-two percent (24/26) of the malignant cells in the lymph nodes stained positively for p53. When the DNA ploidy pattern of the tumour was determined by flow cytometry, the aneuploid tumours in p53 positive and negative groups accounted for 69% and 45%, respectively (P < 0.05). Proliferative activity of the tumour, as measured by Ki 67 labelling, was significantly higher (30.6 +/- 12.0%) in the p53 positive group than that (25.1 +/- 10.7%) in the p53 negative group (P < 0.05). Thus, gastric cancer with a mutant p53 has high proliferative activity and metastasis to lymph nodes will probably occur. PMID- 8439510 TI - The Centre H. Becquerel studies in inflammatory non metastatic breast cancer. Combined modality approach in 178 patients. AB - One hundred and seventy-eight patients with non metastatic inflammatory breast cancer (IBC) have been treated at the Centre H. Becquerel. Median follow up is 67 months (6-178). Every patient received neoadjuvant chemotherapy (mean number of cycles = 4; range: 2-8), followed by a loco regional treatment (radiotherapy = XRT or modified radical mastectomy = S), followed by adjuvant chemotherapy. During this period, the types of chemotherapy and locoregional treatment have been the following: Study I: 64 patients treated with CMF or AVCF and XRT; Study II: 83 patients, treated with either AVCF, FAC or VAC followed by S (n = 38) or XRT (n = 22) in case of complete or partial response, or followed by XRT (23) in case of initial supraclavicular lymph node involvement or lack of response after chemotherapy; Study III: 31 patients treated with FEC-HD + Estrogenic recruitment followed by S and XRT after adjuvant chemotherapy, except seven patients who received XRT (refusal of surgery). Although objective response rates (= 56.2, 73.5 and 93.5% for study I, II and III respectively) are statistically better in the 3rd study, this does not translate in dramatically different disease free survival (median = 16.7, 19 and 22.2 months respectively for study I, II and III) or overall survival (median = 25, 45.7 and 32.6 months respectively for study I, II and III). Analysis of subset of patients without supra clavicular lymph node involvement where neoadjuvant chemotherapy obtained at least a 50% response reveals a median disease free survival and median overall survival of respectively 38.3 and 60.1 months for patients who underwent S vs 19 and 38.3 months for those who received XRT (P = 0.15). These studies suggest that surgery has no deleterious effect on outcome of IBC. Advantage on disease free survival or overall survival from intensive chemotherapy in IBC remains to be proven with appropriate randomised trials. PMID- 8439511 TI - Effect of tamoxifen on Ki67 labelling index in human breast tumours and its relationship to oestrogen and progesterone receptor status. AB - This study aimed to investigate the effect of tamoxifen on breast tumour levels of oestrogen and progesterone receptor (ER and PR) and proliferation as defined by the Ki67 antibody. A group of primary breast cancer patients was randomised to receive either tamoxifen (n = 59) or placebo (n = 44) treatment in the interval between clinic and surgery (median 21 days). Frozen sections of breast tumour biopsies obtained before and after treatment were stained immunocytochemically to obtain the percentage of nuclei containing ER and PR, and a Ki67 labelling index (LI). Tamoxifen-treated patients had a median Ki67 LI of 5.6% in the first biopsy falling to 3.0% in the second biopsy (P < 0.001 by Wilcoxon's matched pairs test), whereas placebo-treated patients had a median Ki67 LI of 5.4% in the first biopsy and 5.75% in the second (no significant difference). No significant differences were observed when the median %ER or %PR staining before and after treatment were compared. The Ki67 LI tended to increase with increasing histological grade and was greater in tumours that were ER - ve compared to those that were ER + ve (> 5% nuclei stained), median 7.8% and 4.3% respectively (P = 0.011 by Mann-Whitney U-test). However, the decline in tumour Ki67 LI following anti-oestrogen treatment failed to correlate with ER and PR status or to predict recurrence over a short follow-up period. To our knowledge, this is the first time that tamoxifen treatment has been shown to reduce the Ki67 LI in human breast tumours in vivo. These data indicate that staining with the Ki67 antibody may be useful in monitoring response to anti-oestrogen therapy. PMID- 8439512 TI - Perception of risk in women with a family history of breast cancer. AB - We present the findings of a pilot study to assess the perception of risk in 155 women with a family history of breast cancer by questionnaire. Only 11% of women were able to identify the correct population risk and more than half were unable to assess their own lifetime risk within 50% of the clinicians' estimate. Although it is probable that women are helped by genetic counselling and if at substantial risk, annual mammography, the psychological impact of assigning true risk and the value of mammography need to be evaluated. PMID- 8439513 TI - Cancer mortality and morbidity in employees of the United Kingdom Atomic Energy Authority, 1946-86. AB - In further analyses of a cohort of 39,718 United Kingdom Atomic Energy Authority employees after 7 more years follow-up, cancer mortality, based on 1,506 deaths in 1946-86, was 20% below the national average. Prostatic cancer mortality showed a statistically significant association with external radiation exposure, largely confined to men who were also monitored for internal contamination by radionuclides other than plutonium. Prostatic cancer mortality was highest in radiation workers at Winfrith. In women monitored for radiation exposure, mortality from cancer of the uterus (including the cervix uteri) was increased relative to other employees, and, showed a statistically significant association with external radiation exposure. While there were some other statistically significant results, as would be expected by chance alone when multiple comparisons are made, there were no other cancer sites with consistently exceptional findings. Point estimates for risk associated with increasing exposure to radiation suggest a decrease of four deaths per 10(4) person-years per Sv for leukaemia and an increase of 20 deaths for all cancers except leukaemia, but confidence intervals indicate that a wide range of values are compatible with the data. Cancer morbidity based on 1,699 registrations in 1971 84 was 12% below the national average. Findings from site-specific analyses largely replicated those of the mortality analyses. PMID- 8439514 TI - Cisplatin in breast cancer. PMID- 8439515 TI - Receptor binding and biological effects of three 125I-iodinated estrogen derivatives in human breast cancer cells (MCF-7). AB - Three 125I-iodinated estrogen derivatives; 16 alpha-[125I]iodo-11 beta-methoxy-17 beta-estradiol ([125I]IME2), E-17 alpha-[125I]iodovinylestradiol ([125I]IVE2) and E-17 alpha-[125I]iodovinyl-11 beta-methoxyestradiol ([125I]MIVE2) were synthesized with high specific activities and their binding characteristics and biological effects were analyzed in vitro using the estrogen-receptor-positive human breast cancer cell line MCF-7. Direct and competitive bindings in a whole cell assay indicated that the three derivatives bound to the estrogen receptor (ER) with high affinity. The dissociation constants of the three compounds were higher than the one found for tritiated E2 suggesting that the presence of the methoxy and the vinyl groups decreased the binding affinity. The decreasing affinity order is: [3H]E2 > or = [125I]IME2 > [125I]IVE2 > [125I]MIVE2. The three unlabeled derivatives as well as E2 have been found to activate the vitellogenin promoter fused to the chloramphenicol acetyl transferase reporter gene transfected into MCF-7 cells. This assay showed that the ER is activated in the presence of the three compounds. Unlabeled IME2 produced stimulatory effects similar to those of E2 on MCF-7 growth in vitro. Unlabeled IVE2 and MIVE2 at concentrations lower than 10(-8) M enhanced MCF-7 growth but at a lower level than E2 and IME2 did. Our results clearly indicate that the three derivatives behave like estrogens and that they would be excellent candidates for imaging or monitoring ER-containing breast tumors. Because its affinity for the ER is greatest, IME2 would be the best-suited of the three as a radiotracer. PMID- 8439516 TI - 3-aminobenzamide protects the mouse thymocytes in vitro from dexamethasone mediated apoptotic cell death and cytolysis without changing DNA strand breakage. AB - Exposure of mouse thymocytes to 1 microM dexamethasone (Dex) resulted in a dramatic increase in the degree of DNA strand breakage up to 80% between 4 to 6 h postincubation. During incubation a marked decrease in the number of total and viable cells as well as an increase in the release of lactate dehydrogenase into medium were detectable, indicating a strong cytotoxicity of Dex on the mouse thymocytes. Agarose gel electrophoresis of DNA from cells exposed to Dex for 6 h clearly demonstrated an increased laddering of DNA fragments multiple of approx. 200 base pairs as a characteristic feature of an apoptosis or programmed cell death. The cytotoxicity of Dex, as judged by the decrease in the viability and increase in the cell lysis, was effectively prevented by 3-aminobenzamide, a potent inhibitor of poly(ADP-ribose) synthesis. Furthermore, the lowering of intracellular NAD levels, which was observable in the present study most probably as a result of activation of poly(ADP-ribose) synthesis due to Dex-mediated DNA strand breakage, was also specifically prevented by the inhibitor, although the DNA strand breakage itself was not affected under these conditions. Our present results indicate that the Dex-mediated thymocyte death and cytolysis and probably intrathymic apoptotic thymocytolysis could be attributable primarily to the loss of intracellular NAD. PMID- 8439517 TI - Azasteroids as inhibitors of testosterone 5 alpha-reductase in mammalian skin. AB - Elevated levels of testosterone 5 alpha-reductase (5 alpha-R) and its product, dihydrotestosterone are associated with a number of androgen-dependent skin conditions. A series of 4-azasteroids were tested in vitro as inhibitors of 5 alpha-R in the isolated anagen human hair follicle. Major structural requirements for maximal 5 alpha-R inhibitory activity include a 4-methyl-4-aza moiety and a bulky, lipophilic side chain at C-17. Only one compound, 17 beta-N,N diethylcarbamyl-4-methyl-4-aza-5 alpha-androstan-3-one (4-MA), was found to be a potent 5 alpha-R inhibitor in all tissues studied: human hair follicles, foreskin (Ki = 3 nM), genital fibroblasts (Ki = 12 nM), and prostate. 17 beta Hydroxysteroid dehydrogenase activity was not inhibited by 4-MA. With the exception of 4-MA, azasteroid IC50s varied widely in human prostate vs skin, suggesting the possible existence in man of at least two 5 alpha-R isozymes. Finasteride [N(1,1-dimethylethyl)-3-oxo-4-aza-5 alpha-androst-1-ene-17 beta carboxamide], a delta 1 orally active, specific 5 alpha-R inhibitor exhibiting no affinity for the androgen receptor, was only modestly active in the hair follicle microassay (IC50 = 200 nM). However, it was a potent in vitro inhibitor of human foreskin and prostate 5 alpha-R. Orally administered to rats finasteride inhibited 5 alpha-R in skin. A vasodilator used to treat male pattern baldness (MPB), minoxidil, was found to be a weak inhibitor of human hair follicle 5 alpha R (IC50 = 1000 nM). 5 alpha-R activity in frontal scalp hair follicles from a MPB subject was four times higher than in occipital follicles. 4-Azasteroids are efficient inhibitors of human skin 5 alpha-R and offer promise for the treatment of acne, hirsutism and MPB. PMID- 8439518 TI - Binding affinities of mometasone furoate and related compounds including its metabolites for the glucocorticoid receptor of rat skin tissue. AB - The binding affinities of mometasone furoate (MF), its metabolites and related compounds for the glucocorticoid receptor of rat epidermis and dermis were measured. MF and its main metabolite exhibited binding affinities higher than those of alclomethasone dipropionate (ADP) and betamethasone dipropionate (BDP), but equivalent to betamethasone 17-valerate (BMV). For compound I (metabolite of MF), ADP, BDP and BMV, the binding affinity was found to be higher in epidermis relative to dermis. This difference in the dermal/epidermal binding ratio may be a favorable sign leading to a possible reduction of dermal collagen atrophy, a known side effect of glucocorticoids. In structure-binding relationship studies, esterification of the 17-OH by furoylation and introduction of the 9 alpha-Cl caused a marked increase of the binding affinity, whereas the 6 beta hydroxylation led to a pronounced decrease. PMID- 8439519 TI - Inheritance of androgen program of male-specific expression of unusual estrogen binding protein by daughter hepatocytes at rat liver regeneration. AB - A possibility of inheritance of androgen and basic genetic programs at the level of unusual estrogen-binding protein (UEBP) by daughter hepatocytes was investigated. Liver regeneration after partial (2/3) hepatectomy or after selective poisoning of hepatocytes of the central zone of hepatic lobules with CCl4 in adult rats were used as models of total and zonal proliferation of hepatocytes, respectively. UEBP content and the pattern of its tissue expression in the course of liver regeneration were monitored by radioligand and immunocytochemical technique. In animals of all groups possessing the androgen program of UEBP expression (intact, castrated and/or hypophysectomized males, and ovariectomized females treated with androgen) UEBP content was shown to be similarly high before initiation and after completion of liver regeneration. Unlike in males, in androgenized females a transient 4-fold increase of UEBP concentration on day 4 after partial hepatectomy was observed. In animals with a basic genetic program at the level of this protein (ovariectomized females, neonatally castrated males) only trace amounts of UEBP were observed in intact as well as in regenerated liver. The data were confirmed by immunocytochemical technique. A gradient mode of distribution of UEBP-contained cells within hepatic lobules with the highest specific staining around central veins was found by immunocytochemical technique in males. Specific staining of centrolobular and periportal hepatocytes was 7- to 10-fold in intact, and 4- to 6-fold in castrated and/or hypophysectomized males. In intact females specific staining was distributed uniformly at extremely low levels similar to that in periportal hepatocytes of males. Androgen administration to ovariectomized females stimulated a significant and stable increase of UEBP content in two layers of hepatocytes surrounding the central vein. Profiles of specific staining of hepatocytes within the hepatic lobules similar to that in control animals were observed after the completion of liver regeneration of different groups of rats. The results obtained suggest all the hepatocytes to be targets for androgen programming, natural in males or experimental in females, while the extent of expression of this program depends on the position of a hepatocyte within the liver lobules and the sex of the animal. PMID- 8439520 TI - A localization study of the cytochrome P-450(21)-linked monooxygenase system in adult rat brain. AB - Immunohistochemical studies were performed to investigate the localization of the cytochrome P-450(21)-linked monooxygenase system in rat brain using a specific antibody against bovine adrenal cytochrome P-450(21) (P-450XXIA1), which was purified electrophoretically as a single protein band and with a heme content of 18.0 nmol/mg protein from adrenocortical microsomes. The cytochrome P-450(21) was found to be mainly localized in the tractus reticulothalamicus and other ascending fibers in adult rat brains. This finding indicated that deoxycorticosterone or its derivatives could be implicated in the regulation of consciousness and the induction of an anesthetic effect. PMID- 8439521 TI - Secretion by the human testis of epitestosterone, with its sulfoconjugate and precursor androgen 5-androstene-3 beta,17 alpha-diol. AB - Epitestosterone (ET) and testosterone (T), free and sulfoconjugated, as well as 5 androstene-3 beta,17 alpha-diol (5AD3 beta 17 alpha) and its 17 beta-epimer have been analyzed, by gas chromatography-mass spectrometry with stable isotope dilution, in peripheral and spermatic venous plasma of patients with left varicocele. All these androgens are secreted by the testis as evidenced by the significant concentration gradients between peripheral and spermatic venous plasma. Half of the daily ET production is ascribed to the testis, while 95% of T sulfate and roughly 70% of ET sulfate are also of testicular origin. Significant correlations between ET and 5AD3 beta 17 alpha are an indication that the 5-ene pathway is also operative for ET biosynthesis. High ratios of spermatic to peripheral venous plasma levels of ET and 5AD3 beta 17 alpha are also related to the high clearance rates of 17 alpha-hydroxy-androgens. PMID- 8439522 TI - Long-term administration of testosterone enanthate to normal men: alterations of the urinary profile of androgen metabolites potentially useful for detection of testosterone misuse in sport. AB - Doses equivalent to 18, 72 and 216 mg testosterone (T)/week were administered for 6 months to eugonadal men. Urinary excretions of androgen glucuronides (G) were quantitatively analyzed by gas chromatography-mass spectrometry with stable isotope dilution during periods of control (without hormone treatment), T administration and recovery. The lowest dosage T administration did not affect the androgen profile, while higher dosages generally increased urinary excretions of T metabolites (TG, T sulfate, glucuronides of androsterone, etiocholanolone, 5 alpha- and 5 beta-androstane-3 alpha,17 beta-diol) and decreased excretions of conjugates of epitestosterone (ET) and its precursor androgen 5-androstene-3 beta,17 alpha-diol. A dose-dependent decrease of urinary LH in response to T was also observed. The ratio (T/ET)G, which is the sole official criterium for assessment of T self-administration by athletes, increased above the threshold value of 6 in most of the subjects, but not all, after the two highest dosage T regimens, and returned to normal during the recovery period. False positive or negative testing emphasizes the need for improvement of testing procedures. In this regard, valuable complementary information may be gained from ratios such as TG/ET(Total), TG/LH, (T/5-androstene-3 beta,17 alpha-diol)G, (5 alpha/5 beta)androstane-3 alpha,17 alpha-diol and (5 alpha/5 beta)androstane-3 alpha,17 beta-diol. PMID- 8439523 TI - A study of androgen biosynthesis by the human testis in vitro. AB - The biosynthetic pathways in human testicular tissue have been studied extensively in our laboratory without the use of radioisotopes. Experiments were conducted with normal testicular tissue from patients undergoing orchiectomy for prostatic cancer. These studies have shown that the preferred pathway of testosterone biosynthesis is influenced by the nature and concentration of cofactor added to the incubation medium. Four enzymes are involved in the transformation of pregnenolone to testosterone, that is, 3 beta-hydroxysteroid dehydrogenase, 17 alpha-hydroxylase, C17-C20 lyase and 17 beta-hydroxysteroid oxidoreductase. Our studies show that the 4-ene pathway predominates in the biosynthesis of testosterone from pregnenolone. Analysis of several samples of human testicular vein blood supports the contention that 4-androsten-3,17-dione is the immediate precursor of testosterone. PMID- 8439524 TI - Inhibition study of human placental aromatase with 3-deoxy- and 6-oxo-steroids using [1 beta-3H]16 alpha-hydroxyandrostenedione as a substrate: a comparison to that using [1 beta-3H]androstenedione. AB - Inhibition of aromatase activity in human placental microsomes with 3-deoxy- (1, 2, 4, 6 and 8), 6-oxo- (3, 5 and 9), and 16 alpha-bromo- (7) steroids was studied using [1 beta-3H]16 alpha-hydroxyandrostenedione (16 alpha-OHAD) as a substrate and compared to that with the conventional substrate, [1 beta-3H]androstenedione. All the steroids inhibited both 16 alpha-OHAD and [1 beta-3H]androstenedione aromatization in a competitive manner. Based on Ki/Km ratios obtained in both series of experiments, their relative inhibitory activities in the series with 16 alpha-OHAD were not necessarily identical with those in the other series. The results would be important to understand the relationship of structure to function of aromatase in human placental microsomes. PMID- 8439525 TI - DNA changes in mechanically deformed osteoblasts: a new hypothesis. AB - The available evidence strongly implicates the osteoblast as the key regulator of bone remodelling activity. Since orthodontic tooth movement is a potent inducer of such activity it is relevant to study the effect of mechanical forces on this cell population. The development of a model for mechanically deforming monolayer cultures of cells is described. The effect of mechanical forces on osteoblast like cells was examined by a number of parameters. Changes in DNA synthesis seen in short-term experiments were at variance with previous published data. The data derived from longer term experiments was in close agreement with in vivo models; intermittent forces producing an increase in DNA synthesis when compared to static or continuous forces. These changes are discussed in relation to current perspectives of second messenger activation by mechanical strain. Prostaglandins did not appear to mediate these events. There was also no evidence that synthesis of the cytokine, interleukin-1 (IL-1), or the metalloproteinase, collagenase was altered by mechanical forces. PMID- 8439526 TI - A comparison of five different methods for describing sagittal jaw relationship. AB - Analysis of sagittal jaw relationship is important in orthodontic diagnosis and treatment planning, and can be investigated by angular or linear parameters. In the present study an analysis was performed using profile cephalograms of 40 children with skeletal Class II malocclusion. A correlation analysis is presented, involving five different methods of expressing sagittal jaw relationships. Whilst some degree of agreement could be noted, it was not possible to suggest a pair of measurements, which in combination, could give a more accurate picture of sagittal jaw relationships. PMID- 8439527 TI - Horizontal skeletal typing in an ethnic Chinese population with true Class III malocclusions. AB - Eighty Chinese adults with true Class III malocclusions were analysed cephalometrically to determine the percentage in each horizontal skeletal subtype. The maxillary and mandibular skeletal bases for each subject were analysed using angular (SNA/SNB) as well as linear (point A/B to McNamara's line) criteria. Results indicated that mandibular hyperplasias with normal anteroposterior maxillary position comprised the majority of true Class III malocclusions. While the majority of Class III in males were due to hyperplastic mandibles and normal maxillary antero-posterior relationship, most of the female Class III malocclusions were due to normal mandibles and hypoplastic maxillae. There was no significant difference between the incidence in Class III subtypes when using either angular or linear criteria. PMID- 8439528 TI - The use of occlusal indices in assessing the provision of orthodontic treatment by the hospital orthodontic service of England and Wales. AB - This retrospective study was carried out to assess the need for orthodontic treatment and the standard of treatment provided by a sample of 17 hospital-based orthodontic departments. A total of 1630 sets of patients records were collected and analysed for orthodontic treatment need and standard of treatment with the Index of Orthodontic Treatment Need and the PAR index, respectively. The data were analysed with a variant of analysis of covariance using linear modelling techniques. In general terms it appeared that the hospital service provided treatment of a high standard, in terms of dento-occlusal change, to a caseload of patients that were in need of treatment. The effectiveness of treatment provision was influenced by the grade of operator, the choice of treatment methods and by the departmental attitudes and aspirations. PMID- 8439529 TI - Attitudes of orthodontic postgraduates to MSc research projects--a retrospective survey. AB - A questionnaire survey of 103 past orthodontic postgraduate students from seven U.K. institutions, was undertaken to determine the perceived value of M.Sc. research projects in relation to the amount of effort required by students to complete their reports. Seventy-nine (76.7 per cent) replies were received. The majority of the respondents (47, 59.5 per cent) had trained at the Eastman Dental Hospital, although this did not markedly affect the results statistically other than where the graduates were given a choice of MSc subject (P < 0.001). Most postgraduates (42, 54.6 per cent) had found their projects interesting and useful, but 42 (54.6 per cent) claimed to have spent more than 30 per cent of their working time producing them. Forty-four (55.7 per cent) commented that they had problems with the project; of these, there were complaints of insufficient time (23.5 per cent), material (14.7 per cent), data (13.3 per cent), inadequate supervision or direction (26.5 per cent), and interference with clinical time (16.4 per cent). Twenty (25.3 per cent) had carried out further work on their projects, but only three (2.9 per cent) had gone on to complete a Ph.D. PMID- 8439530 TI - An unsupervised straight wire appliance--a case report. AB - The remarkable potential of the straight-wire appliance to provide continuing tooth movement is demonstrated. A 14-year-old male patient was fitted with an upper appliance which remained in situ, unsupervised, for 14 months. An unexpected degree of space closure and overjet reduction occurred. Factors that may have contributed to this unexpected degree of improvement are considered. PMID- 8439531 TI - Persistent paradoxes. PMID- 8439532 TI - An ideal preformed archwire? PMID- 8439533 TI - Preformed round, rectangular and square stainless steel archwires. A comparison of those available from UK supply houses. PMID- 8439534 TI - A pre-transition-state mimic of an enzyme: X-ray structure of adenosine deaminase with bound 1-deazaadenosine and zinc-activated water. AB - The refined 2.4-A structure of adenosine deaminase, recently discovered to be a zinc metalloenzyme [Wilson, D. K., Rudolph, F. B., & Quiocho, F. A. (1991) Science 252, 1278-1284], complexed with the ground-state analog 1-deazaadenosine shows the mode of binding of the analog and, unexpectedly, a zinc-activated water (hydroxide). This structure of a pre-transition-state mimic, combined with that previously determined for the complex with 6(R)-hydroxy-1,6-dihydropurine ribonucleoside, a nearly ideal transition-state analog, sheds new understanding of the precise stereospecificity and hydrolytic catalysis of an important and well-characterized member of a large group of zinc metalloenzymes. As both of these excellent mimics were generated in the active site, they demonstrate a powerful means of dissecting the course of an enzymatic reaction by direct crystallographic analysis. PMID- 8439535 TI - Titration of histidine 62 in R67 dihydrofolate reductase is linked to a tetramer< ->two-dimer equilibrium. AB - R67 dihydrofolate reductase (DHFR) is an R-plasmid encoded protein that confers clinical resistance to the antibacterial drug trimethoprim. To determine whether an acidic titration in kinetic pH profiles is related to titration of histidines 62, 162, 262, and 362, the stability of tetrameric R67 DHFR has been monitored as a function of pH. For the pH range 5-8, tetrameric R67 DHFR reversibly dissociates into dimers, as monitored by ultracentrifugation and molecular sieving techniques. From the crystal structures of dimeric and tetrameric R67 DHFR [Matthews et al. (1986) Biochemistry 25, 4194-4204] (Narayana, Matthews, and Xuong, personal communication), symmetry-related histidines 62, 162, 262, and 362 occur at the two dimer-dimer interfaces and protonation of these residues could destabilize tetrameric R67 DHFR. Ionization of these histidines was confirmed by monitoring the chemical shifts of the C2 proton in NMR experiments, and best fits of an incomplete titration curve yield a pKa of 6.77. Since tryptophans 38, 138, 238, and 338 also occur at the dimer-dimer interfaces, fluorescence additionally monitors the tetramer-two dimers equilibrium. When fluorescence was monitored over the pH range 5-8, a protein concentration dependence of fluorescence was observed and global fitting of three titration curves yielded Kd = 9.72 nM and pKa = 6.84 for the linked reactions: [formula: see text] Modification of H62, H162, H262, and H362 by diethyl pyrocarbonate stabilizes dimeric R67 DHFR and causes a 200-600-fold decrease in catalytic efficiency. Decreased catalytic activity in dimeric R67 DHFR is presumably due to loss of the putative single active site pore found in tetrameric R67 DHFR. PMID- 8439536 TI - Structure and dynamics of the acid-denatured molten globule state of alpha lactalbumin: a two-dimensional NMR study. AB - Two-dimensional 1H-NMR spectroscopy has been used to study the acid-denatured molten globule (A-state) of alpha-lactalbumin. The NMR spectra show that chemical shift dispersion is limited but significantly greater than that expected for a random coil conformation. The small chemical shift dispersion of side-chain resonances in the A-state together with line broadening associated with conformational averaging indicates that most of the long-range tertiary structure in the A-state is likely to be nonspecific. Side-chain resonances in the A-state are generally shifted somewhat upfield of random coil values; this and the observation of a large number of interresidue NOEs, however, indicate that some side-chain interactions, at least at the level of hydrophobic clustering, exist in the A-state. Analysis of NOESY spectra shows no evidence for an ordered structure for either of the two major clusters of aromatic residues which in the native structure make up part of the hydrophobic core of the helical domain of the native protein. A new aromatic cluster in the A-state which results from rearrangement of the side chains of Tyr103, Trp104, and His107 from their native state positions was, however, detected by a number of well-defined interresidue NOE effects. Similar NOE patterns are observed in a peptide corresponding to residues 101-110 of alpha-lactalbumin in trifluoroethanol, suggesting that the non-native structure in the 101-110 region of the A-state is not dependent on specific interactions with the rest of the chain. Trapping experiments indicate that amide protons from regions of the sequence which in the native state are helical are among those strongly protected from solvent exchange in the A-state; those from one of the helices (the C helix) were specifically identified. Taken together, these results reinforce a model of the A-state which has stable regions of localized secondary structure but a largely disordered tertiary structure. PMID- 8439537 TI - Retinol uptake from retinol-binding protein (RBP) by liver parenchymal cells in vitro does not specifically depend on its binding to RBP. AB - The uptake characteristics of both the retinol and retinol-binding protein (RBP) moieties of the retinol-RBP complex by liver parenchymal cells (PC) in vitro were studied to assess whether retinol uptake is mediated by a cell-surface receptor for RBP. At 37 degrees C as well as 4 degrees C, [3H]retinol uptake from [3H]retinol-RBP showed a time-dependent increase, and was not saturable at concentrations exceeding the physiological concentration by more than a factor of 2 (3 microM). Uptake of [3H]retinol was not inhibited by a 10-fold molar excess of unlabeled retinol-RBP. Cell association of 125I-RBP at 37 and 4 degrees C was low and showed no time dependence. In addition, the association of 125I-RBP was not saturable at concentrations up to 3 microM. These data do not support the existence of a cell-surface receptor for RBP on rat liver PC. The uptake of [3H]retinol from RBP was also compared to the uptake of retinol from cellular retinol-binding protein (CRBP) and lactoglobulin. Uptake characteristics of [3H]retinol from CRBP and lactoglobulin were similar to that of [3H]retinol from RBP. Furthermore, a similar percentage of the [3H]retinol taken up by PC was metabolized into retinyl esters, irrespective of its carrier. These data suggest that the uptake of retinol and its subsequent metabolic processing do not depend on binding to RBP. The low level of cell association of 125I-binding proteins was not due to uptake, degradation, and secretion of ligand by PC. This suggests that retinol is dissociated from its binding protein before uptake by PC. PMID- 8439538 TI - Mutagenesis by the (+)-anti-diol epoxide of benzo[a]pyrene: what controls mutagenic specificity? AB - Mutagenesis by (+)-anti-benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide [(+)-anti B[a]PDE], an important mutagenic/carcinogenic metabolite of benzo[a]pyrene (B[a]P), is being studied in order to understand the factors that influence mutagenesis both quantitatively and qualitatively. A new mutational system, which permits the selection of supF- mutations in an Escherichia coli plasmid, pUB3, was used. The work described herein is an extension of previous work, which involved plasmid adduction and then immediate transformation (Rodriguez & Loechler, 1993), and began with the observation that mutation frequency (MF) decreased approximately 2-fold when the (+)-anti-B[a]PDE-adducted plasmid pUB3 is either (1) frozen and then thawed prior to transformation or (2) heated at 80 degrees C for 10 min prior to transformation. Several results suggest that this decrease is not due to the loss of labile adducts. To begin to understand this phenomenon, the mutagenic spectra are compared for (+)-anti-B[a]PDE in supF for the unheated (187 mutants), the freeze/thawed (134 mutants), and the heated (254 mutants) samples. In general, freeze/thawing and heating cause a decrease in all classes of mutations. Considering substitution mutations at G.C base pairs, which predominate, the mutagenic specificity for the combined data sets is GC-->TA (57%), GC-->AT (23%), and GC-->CG (20%). This raises the question, how does (+) anti-B[a]PDE generate this complex mutagenic specificity, which contrasts with the situation for, e.g., simple methylating agents? One factor is that mutagenic specificity at a particular guanine residue can be influenced by the base on its immediate 5'-side, most notably where mutations are virtually exclusively restricted to GC-->TA in 5'-TG-3' sequence contexts. One unexpected finding may provide additional insight. G115 in supF, which is the major hot spot for base pairing mutagenesis, is the only site where the qualitative pattern of mutagenesis is significantly affected by heating the (+)-anti-B[a]PDE-adducted plasmid prior to transformation. Without heating, G115-->T mutations predominate, but following heating there is a statistically significant increase in the fraction of G115-->A and G115-->C mutations. The most likely model to explain this and other results is (1) a particular DNA adduct can adopt multiple conformations, (2) the conformation adopted by an adduct can be influenced by various factors, including DNA sequence context, as well as heating and freeze/thawing, and (3) each of these conformations can cause a different pattern of mutation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8439539 TI - Promoter-specific synthetic photoendonuclease: rose bengal-labeled T7 RNA polymerase. AB - We have constructed a synthetic photoendonuclease composed of T7 RNA polymerase linked to rose bengal. The promoter-specific polymerase confers site-specific binding, and the photosensitizer rose bengal allows light-induced DNA cleavage. Using a gentle labeling procedure, we find that the polymerase can be labeled with 1-30 rose bengals. Polymerase labeled to about 8 rose bengals per molecule retains the same efficiency and specificity of binding to promoter-containing DNA as unlabeled polymerase. At this level of rose bengal substitution, the synthetic endonuclease, in the presence of visible light, specifically cleaves linear or supercoiled DNA containing a T7 promoter. It induces frank single-strand breaks, rather than labile sites convertible to breaks upon additional treatments. Neither the free rose bengal moiety not bonded to polymerase nor the free (not bound to DNA) rose bengal-substituted polymerase cleaves DNA. Although rose bengal is an efficient generator of singlet oxygen, depletion of oxygen from reaction mixtures increases the cleavage rate. This indicates that singlet oxygen cleavage is not a major mechanism of DNA nicking by the synthetic endonuclease. At higher levels of rose bengal substitution, the labeled polymerase shows decreased binding efficiency and increased nonspecific binding to DNA without a T7 promoter; the specificity of DNA cleavage also decreases. These results indicate that the site specificity of rose bengal photocleavage by the synthetic endonuclease results from specific binding of the polymerase, and thus rose bengal photonicking reflects polymerase binding. PMID- 8439541 TI - A hydrogen-bonding network modulating enzyme function: asparagine-194 and tyrosine-225 of Escherichia coli aspartate aminotransferase. AB - The electron distribution within the coenzyme or coenzyme-substrate conjugate needs to be properly regulated during the catalytic process of aspartate aminotransferase (AspAT). Asn194 and Tyr225 may function in regulating the electron distribution through hydrogen-bonding to O(3') of the coenzyme, pyridoxal 5'-phosphate (PLP) or pyridoxamine 5'-phosphate (PMP). The roles of Tyr225 have already been explored by site-directed mutagenesis (Inoue et al., 1991; Goldberg et al., 1991). In the present studies, the mutant enzymes Asn194- >Ala and Asn194-->Ala + Tyr225-->Phe were analyzed kinetically and spectroscopically and were compared with the wild-type and Tyr225-->Phe enzymes. The kinetic studies showed that Asn194 is not essential for AspAT catalysis, although the Kd values for the substrates were increased by 10- to 50-fold upon the replacement of Asn194. The measurements of the absorption and fluorescence excitation spectra revealed that the ratio of an enolimine to a ketoenamine form was considerably increased as a tautomeric form of the protonated PLP in the active site of the double mutant enzyme. The pH-pKd relationship for the binding of maleate to AspAT could be explained by a simple thermodynamic cycle where only one ionizing group (the imine nitrogen of the internal aldimine bond) affects the binding of maleate. The analyses of the pH-pKd curves for the wild-type and mutant enzymes showed that (i) the hydrogen bond between O(3') of PLP and Asn194 is weakened by the binding of maleate to AspAT, while the hydrogen bond between O(3') and Tyr225 is not changed, and that (ii) the replacement of Asn194 causes some effect hampering the binding of maleate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8439540 TI - Product dependence of deuterium isotope effects in enzyme-catalyzed reactions. AB - Theory for enzyme-catalyzed reactions is developed for the dependence on product concentration of deuterium isotope effects on V and V/K. Generally, a product that decreases the off-rate for a second product to zero causes the isotope effect on V/K to decrease to DKeq and that on V to decrease to a value between 1 and DKeq. If the second product off-rate is decreased to a finite value, DV and D(V/K) will decrease to a value greater than DKeq, while if there is no effect on the off-rate for the second product, DV and D(V/K) will not change. Interestingly, for a ping-pong mechanism, the presence of the product that provides a reversible connection between the isotope-sensitive step and the isotope-insensitive half-reaction will give an isotope effect on V/K for the latter. (In the absence of the product, the isotope effect on V/K for the isotope insensitive half-reaction will be unity.) Theory is supported with data for alcohol and lactate dehydrogenases. For lactate dehydrogenase, D(V/Kpyruvate) decreases from 1.93 +/- 0.02 at zero to 1.16 +/- 0.02 at infinite lactate concentration, while DV decreases from a value of 1.75 +/- 0.03 at zero to a value of 0.93 +/- 0.05 at infinite lactate concentration. Thus, it appears that the pathway in which lactate is released first is greatly preferred, but the pathway in which NAD+ is released before lactate is observed at high lactate concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8439542 TI - Environments and mechanistic roles of the tyrosine residues of delta 5-3 ketosteroid isomerase. AB - Delta 5-3-Ketosteroid isomerase (EC 5.3.3.1) from Pseudomonas testosteroni converts delta 5-3-ketosteroids to delta 4-3-ketosteroids by a stereoselective and conservative transfer of the 4 beta-proton to the 6 beta-position. The 10(9.5)-fold enzymatic rate acceleration can be attributed to a concerted rate limiting enolization in which Tyr-14 and Asp-38, positioned orthogonally, act as general acid and base, respectively. The pKa value of the phenolic hydroxyl group of Tyr-14 of the Y55F/Y88F double mutant is 11.6 +/- 0.2 by UV titration. However, the fluorescence titration of Tyr-14 shows biphasic sigmoidal behavior with apparent pKa values of 9.5 and 11.5. This suggests the assistance of a basic residue at the active site, possibly a lysine or tyrosine residue. Mutation of each of the four lysine residues K119L, K108Q, K92Q, and K60Q lowered specific activities only slightly to between 43% and 98% of the wild-type enzyme. Similarly, mutations of Tyr-55, Tyr-88, or both to phenylalanine led to only 2-4 fold reductions in catalytic activity. These findings suggest that despite the enormous difference between the pKa value of Tyr-14 (11.6) and that of the 3 carbonyl group of the steroid (ca. pKa-7), the reaction may rely on the concerted participation of Tyr-14 and Asp-38 only. The apparent pKa value of 9.5 in the fluorescence titration of Tyr-14 and in kinetic measurements probably results from conformational changes of the enzyme. The unusually high pKa value of Tyr-14 of 11.6 +/- 0.2 was used to estimate a local dielectric constant of 18 +/- 2 near this residue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8439543 TI - Binding of a synthetic apolipoprotein B-100 peptide and peptide analogues to chondroitin 6-sulfate: effects of the lipid environment. AB - The association of apolipoprotein B-100 (apoB-100) containing lipoproteins, low density lipoproteins (LDL), very low density lipoproteins (VLDL) and lipoprotein(a) [Lp(a)] with chondroitin sulfate-rich proteoglycans (CSPG) of the arterial intima appears to contribute significantly to lipoprotein disposition during atherogenesis. Using frontal elution analysis and competition experiments, we have previously suggested that the apoB-100 segment RLTRKRGLK (3359-3367) is a mediator of the association between LDL and arterial CSPG. Here, with direct binding measurements and fluorescence titrations, we evaluated the effect of the lipid environment on the affinity of the above apoB-100 segment for chondrotin 6 sulfate (C6S). We synthesized a secondary model peptide with hydrophobic tails which allowed its binding to lipid vesicles and lipoproteins (VVWRLTRKRGLKVVV). When associated with lipid vesicles, this peptide showed a higher affinity (KD = 3.9 microM) for C6S than the free peptide (KD = 18.7 microM). However, the affinity was still lower than that of LDL (KD = 0.21 microM). The increase in affinity for the peptide after association with lipid vesicles indicates that the secondary structure induced by its association with lipid vesicles is a significant modulator of the affinity for glycosaminoglycans. When bound to LDL and VLDL subfractions, VVWRLTRKRGLKVVV increased the affinity of the lipoproteins for C6S. The results suggest that, with the proper secondary structure induced by the lipid environment, the segment RLTRKRRGLK of apoB-100 is an important determinant of the association of LDL and VLDL with glycosaminoglycans but that probably other basic segments contribute to this interaction. PMID- 8439544 TI - Kinetics of the inhibition of human leukocyte elastase by elafin, a 6-kilodalton elastase-specific inhibitor from human skin. AB - We have investigated the kinetics of inhibition of human leukocyte elastase by elafin, a small protein originally isolated from human skin. A single inhibitor molecule was found to bind to a single site on the protease, blocking the reactive serine at the enzyme's catalytic center. Association of the enzyme with the inhibitor proceeds via a single bimolecular process, with a second-order rate constant of 3.6 x 10(6) M-1 s-1 at pH 8.0 and 25 degrees C. Dissociation of the enzyme-inhibitor complex regenerates fully active enzyme with a first-order rate constant of 6.0 x 10(-4) s-1. The species of elafin which is released from the complex simultaneously with the enzyme was estimated to be at least 99.8% active, with association and dissociation kinetics identical to preparations of the inhibitor which had never been exposed to the enzyme. Ki, the equilibrium dissociation constant of the enzyme-inhibitor complex, decreases from 6.7 x 10( 9) to 2.0 x 10(-10) M as the pH is increased from 5.4 to 9.0. The effect of pH on the association rate constant reveals that the reaction rate is dependent on the concentration of the unprotonated form of a group with pKa of 6.8, which we have assigned to the histidine which forms part of the catalytic triad in the enzyme's active site. On the basis of these findings, we conclude that elafin is a potent, substrate-like, but fully reversible inhibitor of human leukocyte elastase. PMID- 8439545 TI - Identification of a guanine binding domain peptide of the GTP binding site of glutamate dehydrogenase: isolation with metal-chelate affinity chromatography. AB - Photoaffinity labeling with [alpha-32P]8N3GTP and [gamma-32P]8N3GTP was used to identify the guanine binding domain of the GTP regulatory site within glutamate dehydrogenase (GDH). Without photolysis, 8N3GTP mimicked the regulatory properties of GTP on GDH activity with 8N3GTP exhibiting a Ki of 5 microM while the Ki for GTP was about 0.6 microM. Under optimal photolabeling conditions saturation of photoinsertion with 1 microgram of GDH revealed an apparent Kd of 9 +/- 4 microM for [gamma-32P]8N3GTP. Photolabeling with this analog could be competitively inhibited with GTP with an apparent Kd of 12 +/- 2 microM. Other nucleotides such as ATP and NAD(P)H could not reduce the amount of photoinsertion as effectively as GTP. ADP could decrease photoinsertion, but only at much higher concentrations. NAD(P)+, GDP, AMP, and GMP had little effect on photoinsertion. Divalent cations Mg2+ and Ca2+ also reduced photoinsertion significantly while the monovalent K+ and Na+ ions had no effect. Aluminum(III)-chelate or iron(III) chelate affinity chromatography and reversed-phase HPLC were used to purify photolabel-containing peptides generated with either trypsin or chymotrypsin. This identified a portion of the guanine binding domain within the GTP regulatory site as the region containing the sequence Ile439 to Tyr454. Photolabeling of this peptide was prevented 91% by the presence of 300 microM GTP during photolysis. Lys445 was not identified in sequence analyses of the photolabeled peptides. Also, trypsin was unable to cleave the photolabeled peptide at this site. These results suggest that Lys445 may be the residue modified by [alpha 32P]8N3GTP. PMID- 8439546 TI - Society for Adolescent Medicine. Annual meeting program issue. March 18-21, 1993, Chicago, Illinois. Abstracts. PMID- 8439547 TI - Conformational changes in oligo-nucleotides upon binding to a peptide representing the N-terminal region of a viral coat protein. An optical spectroscopy study. AB - Conformational changes of the oligonucleotides r(A)12, d(GC)5, and d(AT)5 upon binding to a pentacosapeptide representing the RNA-binding N-terminus of the coat protein of cowpea chlorotic mottle virus (CCMV) were studied by using absorption and circular dichroism spectroscopy. The peptide destabilizes the single-stranded structure of r(A)12 at pH 7.2, but disrupts the double-stranded structure of r(A)12 at pH 5.0. However, at pH 4.0, the peptide is not able to disrupt this double-stranded structure. The double-stranded structures of d(GC)5 and d(AT)5 with Watson-Crick base-pairing are stabilized upon binding to the peptide. PMID- 8439548 TI - Purification and characterization of the HU-like protein HPB9 from the Bacillus subtilis nucleoid. AB - The Bacillus subtilis HPB9 is the major heat-stable and acid-soluble protein associated with the nucleoid isolated at low ionic strength. The abundance of the protein in the cell is estimated to about 20,000 monomers per cell (Salti et al. (1985) J. Gen. Microbiol. 131, 581-590). The protein cross reacts specifically with the antiserum against the Bacillus globigii HBg. Moreover, HPB9 is able to introduce negative supercoiling in a relaxed covalently closed circular DNA, in the presence of topoisomerase I as demonstrated by one and two-dimensional electrophoresis. These results indicate that the nucleoid associated protein HPB9 is an HU-like protein and could be involved in the DNA compaction. PMID- 8439549 TI - Characterization of DBPm, a plant protein that binds to DNA containing 5 methylcytosine. AB - A protein (DBPm) has been isolated from nuclear extracts of soybean seeds, cauliflower florets, corn seed, wheat germ, and pea hypocotyl, seeds, apices, roots, and leaves that specifically binds to double-strand DNA containing 5 methylcytosine residues. In electrophoretic mobility shift assays, non-methylated duplex DNAs competed only slightly, while methylated DNAs were strong competitors. Specific binding still occurred after partial proteolysis of DBPm, but not after heating at 45 degrees C. By ultraviolet light-crosslinking and sodium dodecyl sulfate polyacrylamide gel electrophoresis and gel filtration, the size of pea seed DBPm was estimated to be in the range 70-90 kDa. From equilibrium binding studies the equilibrium constant for binding of pea seed DBPm to a 34 bp duplex deoxyoligonucleotide containing 12 5-methylcytosine residues was 1.2 x 10(9) M-1. The binding properties of DBPm make it a good candidate for a plant protein capable of mediating the effects of DNA methylation on the activity of some plant genes. PMID- 8439550 TI - Identification and characterization of a yeast gene encoding an adenylate kinase homolog. AB - Screening for genes homologous to adenylate kinase in the yeast Saccharomyces cerevisiae resulted in the isolation of a homolog of the previously characterized ADK1. The derived protein sequence is most closely related to mammalian GTP:AMP phosphotransferase (adenylate kinase isozyme 3; AK3); this novel gene is therefore named ADK3. Its deletion from the yeast genome does not lead to an observable change in cellular phenotype. A strain defective for both ADK1 and ADK3 is viable. When introduced on a multicopy plasmid into an ADK1-deficient yeast strain, which shows a reduced proliferation rate, ADK3 did not rescue this growth defect. The protein was also highly overexpressed in E. coli cells. However, no change in enzymatic activity was detected in cellular extracts of yeast or bacteria. PMID- 8439551 TI - Structure of the gene encoding human liver cholesterol 7 alpha-hydroxylase. AB - A human cholesterol 7 alpha-hydroxylase gene spanning 17 kb in length which includes the sequence 5' flanking region (6. kb) and that of the entire transcriptional region (10.5 kb) was obtained from two partially overlapping clones (i.e., HG 18 and HG 17) of a human genomic library. The exon-intron boundaries are completely identical with that of rat gene. Several transcriptional factor recognition sequences were observed in the 5' flanking region. PMID- 8439552 TI - A gene coding for a new plant serpin. AB - The barley (Hordeum vulgare) protein Zx gene (3283 bp) has been isolated and sequenced in its entirety. The predicted 398 amino acids (aa) of Zx are 70% identical to barley protein Z4 and show approx. 30% similarity to the animal members of the serpin superfamily. Zx has an Arg-Ser as the putative reactive site. The Zx gene is interrupted by a 971 bp intron located at a position identical to that in Z4. The 5' and 3' noncoding regions as well as the intron show no pronounced sequence similarity to the Z4 gene or other plant genes. PMID- 8439553 TI - Human FLI-1 localizes to chromosome 11Q24 and has an aberrant transcript in neuroepithelioma. AB - The v-ets oncogene family shares a conserved motif, termed the ETS-domain, that mediates sequence-specific DNA binding. This motif is unique among transcription factor families. Using partially degenerate oligonucleotides to highly conserved amino acids in this motif as primers for the polymerase chain reaction, a novel ETS-domain cDNA fragment was generated. This fragment was subsequently used to clone both mouse and human full length cDNAs for this gene. The amino acid sequence of the longest open reading frame showed that this gene was homologous to the mouse FLI-I gene, an ETS family gene activated by Friend erythroleukemia virus insertion. The gene is normally expressed only in hematopoietic cells. The gene was localized to chromosome 11q24, a region of aberrations in Ewing's sarcoma and neuroepithelioma. In the neuroepithelioma cell line TC-32 the FLI-1 transcript is present but has an aberrant structure, indicating that it may be rearranged in neuroepithelioma. PMID- 8439554 TI - Sequence analysis of monkey acrosin-trypsin inhibitor transcripts and their abundant expression in the epididymis. AB - Seven independent cross-hybridizing clones have been isolated from a Macaca fascicularis epididymal cDNA library and their inserts shown to correspond to a secreted inhibitor of the sperm serine proteinase, acrosin. Hybridizing transcripts of approx. 0.6 kb have been shown by Northern blot analysis to be considerably more abundant in the epididymis than the testis. This finding is in surprising contrast to a previous report that human acrosin-trypsin inhibitor mRNA predominates in the testis. PMID- 8439555 TI - Cloning and sequencing of a full length cDNA encoding ovine lipoprotein lipase. AB - A cDNA clone encoding lipoprotein lipase has been isolated from an ovine adipocyte library. Sequencing of this clone has revealed a single open reading frame encoding a 450 amino acid protein. Comparison with known LPL sequences from other species shows a high degree of conservation in the sequence of the protein and in the 5' untranslated region of the DNA sequence. PMID- 8439556 TI - Alteration of superhelical state of DNA by aluminium (Al). AB - The effect of aluminium (Al) on the supercoiled state of pUC18 DNA was studied by ethidium bromide fluorescence and agarose gel electrophoresis. Al at physiologically relevant concentrations relaxed the intact supercoiled DNA as well as the topoisomers induced by chloroquine. EDTA prevented the unwinding effect of Al on supercoiled DNA. Al did not alter the mobility of linear DNA in agarose gels. The implications of this finding in neurological disorders are discussed. PMID- 8439557 TI - Molecular cloning and expression of rabbit pancreatic cholesterol esterase. AB - Rabbit pancreatic cholesterol esterase (CEase, carboxyl ester lipase, EC 3.1.1.3) has been cloned from a lambda gt11 library of adult rabbit pancreatic cDNA. The open reading frame consists of 1788 nucleotides which encodes 576 amino acids of the functional protein and a 20 amino acid leader peptide. When compared to other species, the greatest homology is observed between residues 82-248 with little or no homology at the C-terminal end where proline-glutamate-serine-threonine (PEST) segments are a characteristic feature of the human CEase. Rabbit CEase (RCEase) retains the active-site serine (gxsxg), the active-site histidine and the tentative heparin binding site (KKRCLQ) at similar positions in comparison to pancreatic CEases of other species. When rabbit CEase cDNA is expressed in monkey kidney (COS-7) cells, enzymatic hydrolytic activity is detected in the growth medium as is a 67 kDa protein by Western blotting with polyclonal anti-CEase antibody. Northern blot analysis shows two mRNA (2.2 and 3.2 kb) species. PMID- 8439558 TI - Cloning and structural analysis of genomic DNA for human renal dipeptidase. AB - A genomic DNA for human renal dipeptidase was isolated from a human genomic library using probes for human renal dipeptidase cDNA. The human renal dipeptidase gene, containing ten exons and nine introns, had a total length of approx. 6 kbp. The DNA sequence of these exons was slightly different from that of the human renal dipeptidase cDNA reported by Adachi et al. [1]. From the results of a comparison of the deduced amino acid sequence of each exon with various mammalian renal dipeptidases, the fourth exon was found to be highly conserved (90%). PMID- 8439559 TI - Nucleotide sequence of the p74 gene of a baculovirus pathogenic to the spruce budworm, Choristoneura fumiferana multicapsid nuclear polyhedrosis virus. AB - Polypeptide p74 has been found to be essential for production of virulent occlusion bodies of the baculovirus Autographa californica multicapsid nuclear polyhedrosis virus (AcMNPV). Hybridization with AcMNPV-derived probes has led to the location of the p74 gene in the spruce budworm virus, Choristoneura fumiferana MNPV. Sequence data indicate that CfMNPV p74 is 73% identical to AcMNPV at the nucleotide level and 77% identical at the amino acid level. Elements of predicted secondary structure are also conserved. PMID- 8439560 TI - A rat histone H2B pseudogene is closely associated with the histone H1d gene. AB - A 9 kb EcoRI restriction fragment was isolated from a recombinant phage out of a rat genomic library. This DNA fragment contains a rat H1d histone gene, its flanking sequences and a H2B histone pseudogene closely associated with the H1d gene. A comparison of the H2B pseudogene with human H2B genes flanking regions reveals sequence homologies to a human H2B histone gene (Albig, W. et al. (1991) Genomics 10, 940-948). PMID- 8439561 TI - The 5' sequence of human factor XII gene contains transcription regulatory elements typical of liver specific, estrogen-modulated genes. AB - The human Factor XII gene codes for a serine proteinase synthesized in liver that activates both the coagulation and the fibrinolytic cascades. The nucleotide sequence analysis of a HincII-HincII 3129 bp fragment was performed showing that the FXII promoter region contains neither CAAT and TATA regulatory elements, nor GC islands, but revealing the presence of two tandemly repeated sequences in opposite orientation, two LF-A1 elements typical of the liver specific genes and one estrogen responsive element, that substantiates the observation of Factor XII gene modulation by estrogens. PMID- 8439562 TI - Cloning and characterization of a novel member of protein kinase family from soybean. AB - The cDNA coding for a novel protein kinase from soybean (Glycine max L.), named GmPK6, was sequenced. The primary sequence of GmPK6 consists of 462 amino acids with an N-terminal sequence similar to the central region of Xenopus U1 snRNP 70K protein, and a C-terminal kinase domain representing structural mosaicism with features diagnostic of both protein serine/threonine and tyrosine kinases in eukaryotic organisms. The GmPK6 gene is expressed as 2.5 kb transcript in a variety of tissues. PMID- 8439563 TI - An adenine nucleotide translocator gene from Arabidopsis thaliana. AB - The sequence of an adenine nucleotide translocator (ANT) gene of Arabidopsis contains three introns, the first of which is located upstream of the assumed initiation codon. The presequence characteristic for plant ANTs is processed also in Arabidopsis as suggested by Western blot analysis, most likely at the conserved cleavage site. PMID- 8439564 TI - Isolation and sequence analysis of variant forms of human transcobalamin II. AB - Two cDNA clones (1.9 kb and 1.5 kb, respectively) encoding full length human TC II have been isolated from a human endothelial cell cDNA library and sequenced. The differences between the two clones are the length of the 5' end and the 3' end non-coding regions and the codon at position 198 and 219. Both the clones differ from the recently isolated (human endothelial cell) cDNA for TC II (Platica, O., Janecko, R., Quadros, E.V., Regee, A., Romain, R. and Rothenberg, S.P. (1991) J. Biol. Chem. 266, 7860-7863) in codon 259 and 376 and in their calculated pI values. In vitro transcription followed by translation in a reticulocyte lysate system and SDS-PAGE revealed that the isolated cDNA clones encode a protein of 43 kDa. Upon treatment with canine pancreatic microsomes, the molecular mass of the in vitro translated product was reduced to 41.5 kDa, indicating the presence of an approximately 1.5 kDa signal peptide. This translation product was immunoprecipitated with rabbit anti-serum to human TC II and was able to bind to Cbl-Sepharose beads. The amino acid sequence alignment of TC II with that of other Cbl binding proteins (rat intrinsic factor, human transcobalamin I and porcine haptocorrin) revealed only 33% overall homology. However, there were four regions of greater than 80% homology and two regions of about 60% homology. These regions encompass the majority of the hydrophobic areas of the Cbl-binders. Based on these studies, we suggest that structural basis for the expression of different polymorphic forms of TC II may be due to single point mutations and that TC II, like other mammalian Cbl-binders, have evolved from a common ancestral gene. Furthermore, the Cbl-binding functional domain most probably resides in a hydrophobic pocket which is formed by all or some of the six regions of high homology. PMID- 8439565 TI - Nucleotide sequence of a cDNA for canine beta-spectrin reveals high evolutionary conservation. AB - A cDNA coding for the carboxy-terminus of canine beta-spectrin was isolated from a canine tracheal cDNA library. Analysis of the 3267 nucleotide sequence revealed a single open reading frame coding for 707 amino acids. Comparison of the deduced amino acid sequence to that of the recently reported general isoform of human beta-spectrin (beta G) revealed 98% identity. This high degree of conservation of the general isoform of beta-spectrin illustrates a strong evolutionary selection and should help in identification of sites that are candidates to mediate specialized functions of this general isoform. This is the first report of a cDNA encoding canine beta-spectrin. PMID- 8439566 TI - Determination of mouse major asialoglycoprotein receptor cDNA sequence. AB - Hepatic lectins (asialoglycoprotein receptors) specifically recognize galactose terminated glycoproteins and mediate endocytosis of these molecules. We now report the cloning and sequence of a cDNA encoding murine asialoglycoprotein receptor. It shows high homology with rat and human major receptor forms designated RHL-1 and HHL-1, respectively. They have many conserved regions, such as a transmembrane region, carbohydrate additional region and carbohydrate related region. According to the homology analysis, we concluded that the clone encodes the mouse major asialoglycoprotein receptor (MHL-1). PMID- 8439567 TI - Organization of a rainbow trout estrogen receptor gene. AB - The complete coding region of the estrogen receptor gene was isolated from a rainbow trout genomic library. This gene is divided into ten exons spanning at least 30 kb of genomic DNA. With two exceptions, intron positions are identical to those of the human estrogen receptor gene. The 5' end of the gene, including 1.7 kb of the promoter region, was sequenced. This region exhibits several putative regulatory elements. Localization of a potential estrogen responsive element to the first exon suggests that this gene is autoregulated. This 5' end region was also shown to be able to drive the expression of a CAT reporter gene in Xenopus laevis oocytes. PMID- 8439568 TI - A retropseudogene for non-histone chromosomal protein HMG-1. AB - Southern analysis of the human genome revealed that there are several sequences with homology to the nonhistone chromosomal protein HMG-1. The majority of the HMG-1 sequences are intronless as suggested from the polymerase chain reaction of HeLa DNA. Sequencing of a clone from a human placenta genomic library revealed that the clone was intronless and displayed 99% homology to the human HMG-1 cDNA. The 5' regulatory motif, CCAAT, is present in the clone but there is no TATA-box. Most of the differences between the HMG-1 cDNA sequence and the clone involve point mutations with no interruption of the reading frame. The sequence is flanked at 5' and 3' ends by a 15 nucleotide long direct repeat suggesting that the clone is a processed HMG-1 retropseudogene. Sequence differences between the reading frames of the HMG-1 pseudogene and HMG-1 cDNA indicated that the pseudogene arose relatively late in evolution, approximately one million years ago. The present paper is the first study on a genomic sequence related to HMG-1 genes. PMID- 8439569 TI - Cloning of two isozymes of Trichoderma koningii glyceraldehyde-3-phosphate dehydrogenase with different sensitivity to koningic acid. AB - Koningic acid inhibits glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by binding to the SH group in the active center. The fungus Trichoderma koningii, the producer of koningic acid, contains two GAPDH isozymes (GAPDHs I and II). GAPDH I is inhibited 50% by 1.1.10(-3) M koningic acid, while GAPDH II is inhibited 50% at 6.8 x 10(-6) M. cDNAs of the two isozymes were cloned from T. koningii and their nucleotide sequences were determined. The sequence of coding region and codon usage in both clones were compared with each other and with those of the gene for Aspergillus nidulans GAPDH (enzyme activity is inhibited 50% by 2.7 x 10(-7) M koningic acid). Results indicated that GAPDH II is more closely related to A. nidulans GAPDH than GAPDH I. All essential amino acid residues, except 174 and 181, which are implicated in catalysis and binding of NAD and substrates, were conserved among A. nidulans GAPDH and GAPDHs I and II. Residues 174 and 181 are threonine in both A. nidulans GAPDH and GAPDH II, but alanine and serine, respectively, in GAPDH I. The side-chain of alanine-174 in GAPDH I can not replace threonine-174 functionally as threonine-174 side-chain forms a hydrogen bond with the catalytically essential histidine-176. PMID- 8439570 TI - HGH isoforms: cDNA expression, adipogenic activity and production in cell culture. AB - We have isolated, cloned and achieved functional expression of the cDNAs for both 22 kDa and 20 kDa human growth hormone (hGH) isoforms. A selective cDNA cloning strategy was used to preferentially and simultaneously obtain both hGH 22 kDa and hGH 20 kDa cDNAs. These were used to construct minigenes which were subcloned into two eukaryotic expression vectors and then introduced transiently in COS-7 cells and stably into CHO cells in culture. Transfection assays in COS-7 cells of both minigenes allowed the detection of the secreted hGH 22 kDa and hGH 20 kDa. These hGHs isoforms secreted into COS-7 medium were able to specifically promote differentiation of 3T3-F442A preadipocytes to adipose cells. Adipocyte differentiation was quantitated by Oil Red O triacylglycerol staining or glycerophosphate dehydrogenase activity. Furthermore, stable CHO cell lines have been derived that produce these hGH isoforms. PMID- 8439571 TI - Preliminary characterisation and partial purification of ribosomal gene promoter binding proteins from Trypanosoma brucei. AB - DNA fragments including the promoter region of the major ribosomal RNA gene of Trypanosoma brucei (r-promoter) were identified and subcloned using a synthetic oligonucleotide probe corresponding to the putative core promoter. These fragments were used in mobility shift assays with proteins extracted from T. brucei nuclei, and demonstrated the presence in 0.15 M NaCl extracts of protein(s) with specific binding affinities for the r-promoter region. Binding was stable in the presence of a 100-fold excess of competitor DNA, and occurred at the relatively low salt concentrations (< 50 mM NaCl) characteristic of many enzyme activity optima in this organism. A control DNA fragment not including the r-promoter region was not retarded in the mobility shift assays, and the r promoter-binding activity had a molecular weight of about 140,000. Nuclear extracts from T. brucei contained large amounts of DNase activity, and the promoter-binding proteins were partially purified from the crude extract using ammonium sulphate precipitation, sephacryl S-200 and Heparin-sepharose chromatography. PMID- 8439572 TI - 1,25-Dihydroxyvitamin D-3 destabilizes c-myc mRNA in HL-60 leukemic cells. AB - The differentiation process is accompanied by alterations in the expression of a variety of genes. Monocytic maturation of hematopoietic cells (HL-60) induced by 1,25-dihydroxyvitamin D-3 (1,25(OH)2D3), results in a decrease in steady state c myc mRNA levels. To elucidate the mechanism by which 1,25(OH)2D3 regulates c-myc mRNA expression, transcriptional and post-transcriptional modes of regulation were investigated. No transcriptional regulation was identified, however, 1,25(OH)2D3 appeared to decrease steady state c-myc mRNA levels by increasing its turnover rate. Using actinomycin D to block transcription, the half-life of c-myc mRNA was shown to decrease from 20 min in the absence of 1,25(OH)2D3 to < 5 min in the presence of 1,25(OH)2D3. Cycloheximide reversed the instability induced by 1,25(OH)2D3, prolonging the half-life of c-myc mRNA in both uninduced and 1,25(OH)2D3-induced HL-60 cells to > 60 min, indicating a translational requirement for the destabilization process. Additionally, the c-myc mRNA instability induced by 1,25(OH)2D3 in HL-60 appears to be a specific result of this agent, as indicated by the inability of other monocytic and granulocytic differentiation inducing agents to destabilize c-myc mRNA. PMID- 8439573 TI - Exon skipping in the expression of the gene immediately upstream of N-ras (unr/NRU). AB - The unr (or NRU) gene was identified during investigations of the structure of the N-ras locus in the genome of mammals. A striking feature of the unr/N-ras gene tandem is the short intergenic distance of 150 nucleotides which suggests the possibility of transcriptional interactions between the two genes. At present, the function of the unr gene is unknown, but the predicted translation product shows a distant relationship to a class of DNA binding proteins. Comparison of the two published cDNA sequences, from a human lymphocytic and a rat testis cDNA library, reveals a difference of 31 amino acids in the size of the predicted proteins. We show that this is due to the skipping of exon 5 within the human NRU gene and that a similar phenomenon occurs in the rat unr gene. Exon skipping takes place in all the cells and tissues we have analyzed and generates the predominant form of message, except in the brain where both classes are about as abundant. This exon skipping is independent of other aspects of unr expression such as the choice of the polyadenylation site. PMID- 8439574 TI - Identification of the initiation region of DNA replication in the murine immunoglobulin heavy chain gene and possible function of the octamer motif as a putative DNA replication origin in mammalian cells. AB - An origin region of DNA replication in the murine immunoglobulin heavy chain (IgH) gene was identified by BrdU pulse labeling and PCR amplification methods. The origin region spans about 1000 base pairs and contains the region of transcriptional enhancer in which the octamer sequence is present. The octamer sequence, TNATTTGCAT, is a well-conserved promoter/enhancer element responsible for B cell-specific transcription and is also found in the regulatory sequences for histone genes and others. Its activity as an autonomously replicating sequence was further examined. The murine IgH enhancer region containing the octamer motif was cloned in pUC18 and transfected to HeLa cells. After 60-65 h, the low molecular weight DNA was extracted and the degree to which the plasmid DNA had been replicated in the cells was measured by back-transformation of competent bacteria. Five to ten copies of the plasmid were detected per cell. The replicated plasmid-form DNA could be detected by this assay for at least 7 days after transfection. Synthetic oligonucleotides corresponding to the octamer and the Ephrussi box in the IgH enhancer were also cloned into pUC18 and examined for replicating activity. These plasmids replicated provided that the octamer sequence remained intact, irrespective of the Ephrussi box sequence and of the sites of insertion. These results suggest that the octamer transcriptional element may also serve as a putative origin for cellular DNA replication. PMID- 8439575 TI - Interaction of VspI and Tru9I restriction endonucleases with synthetic oligonucleotides. AB - We describe the properties of two new restriction endonucleases VspI and Tru9I which recognize sequences AT TAAT and T TAA, respectively. The molecular weights, subunit structure and steady-state kinetic constants of these enzymes for native and modified substrates have been determined. We have investigated the interaction of VspI and Tru9I with synthetic oligonucleotides containing modifications either within the recognition sites or around them. These modifications represent the substitution of different DNA deoxyribonucleosides by 1,2-dideoxy-D-ribofuranose, which corresponds to loss of the heterocyclic base while the sugar-phosphate chain remains intact. The effects of the substitutions were analyzed by determining the steady-state kinetic values of the hydrolysis reaction by VspI and Tru9I. The enzymes exhibited Michaelis-Menten kinetics for hydrolyzable substrates. The initial rates (V0) of hydrolysis of modified and unmodified strands of the duplexes varied as a result of these substitutions. The substrates for VspI and Tru9I which contain modifications around the bond to be hydrolyzed or within the complementary nucleosides were unreactive. PMID- 8439576 TI - Differential expression of the mRNAs for the soluble and membrane-bound forms of rabbit cytochrome b5. AB - Total RNA was extracted from a variety of rabbit tissues and reverse transcribed for use in the polymerase chain reaction technique. Using primers designed to amplify the membrane-bound liver cytochrome b5 cDNA, products of two sizes were observed. Both hybridized strongly to a radiolabelled liver cytochrome b5 probe. Sequencing confirmed that the two types of cDNA product encoded the membrane bound and the soluble forms of b5. Messenger RNA corresponding to the soluble cytochrome was detected in the lung, gallbladder and the adrenal gland, as well as in reticulocytes and bone marrow. This was an unexpected finding since the protein has been isolated only from erythrocytes. In contrast, membrane-bound cytochrome b5 mRNA was detected in all tissues tested, suggesting that the corresponding protein is ubiquitous in tissue distribution. PMID- 8439577 TI - The use of computer-assisted diagnosis in cardiac perfusion nuclear medicine studies: a review (Part 2). AB - Computer-assisted diagnosis (CAID) is commonly used to evaluate cardiac nuclear medicine studies such as thallium perfusion scans. Part I of this series (Journal of Digital Imaging, Vol 5, No 4, pp 209-222) reviewed the basic theory underlying CAID in nuclear medicine and its use in planar thallium imaging. This review discusses the application of CAID to SPECT perfusion studies. PMID- 8439578 TI - An integrated picture archiving and communications system-radiology information system in a radiological department. AB - In this report we present an integrated picture archiving and communication system (PACS)--radiology information system (RIS) which runs as part of the daily routine in the Department of Radiology at the University of Graz. Although the PACS and the RIS have been developed independently, the two systems are interfaced to ensure a unified and consistent long-term archive. The configuration connects four computer tomography scanners (one of them situated at a distance of 1 km), a magnetic resonance imaging scanner, a digital subtraction angiography unit, an evaluation console, a diagnostic console, an image display console, an archive with two optical disk drives, and several RIS terminals. The configuration allows the routine archiving of all examinations on optical disks independent of reporting. The management of the optical disks is performed by the RIS. Images can be selected for retrieval via the RIS by using patient identification or medical criteria. A special software process (PACS-MONITOR) enables the user to survey and manage image communication, archiving, and retrieval as well as to get information about the status of the system at any time and handle the different procedures in the PACS. The system is active 24 hours a day. To make the PACS operation as independent as possible from the permanent presence of a system manager (electronic data processing expert), a rule-based expert system (OPERAS; OPERating ASsistant) is in use to localize and eliminate malfunctions that occur during routine work. The PACS-RIS reduces labor and speeds access to images within radiology and clinical departments. PMID- 8439579 TI - Optimized algorithms for displaying 16-bit gray scale images on 8-bit computer graphic systems. AB - Most personal computers contain 8-bit graphic display hardware, whereas most medical gray scale images are stored at 16-bit per pixel integers. To display medical gray scale images on such computers, the 16-bit image data must be remapped into 8-bit gray scale images. This report presents the algorithms and computer code that allow very rapid 16-bit to 8-bit image data transformation. These algorithms are helpful in allowing personal computers with at least the performance of a Macintosh II (Apple Computer, Cupertino, CA) computer to function as low-end picture archiving communication systems or personal workstations. PMID- 8439580 TI - Physician experience with viewing digital radiographs in an intensive care unit environment. AB - After several years of continuous operation, the utility of digital viewing stations as assessed by bedside clinicians has been investigated through the distribution of questionnaires to past and present users. The results of the questionnaire have indicated that the bedside physicians prefer using the workstations over handling film. For evaluation of line placements, chest tubes, and pleural effusions, the physicians prefer softcopy display over hardcopy. However, for analysis of air space disease and diagnosis of pneumothorax, images displayed on the workstation were not believed to be as useful as standard hardcopy. PMID- 8439581 TI - Time comparison of intensive care units with and without digital viewing systems. AB - As hospital radiology departments and intensive care units (ICUs) make plans to use or expand the usage of digital data outside of the radiology department, the need to assess the requirements of the potential recipients in the ICUs has become more important. The present operations in an ICU that uses digital viewing instead of film has been compared with a unit that does not. The difference in time between x-ray exposure and final image viewing was determined in both settings and compared. In this preliminary study, significant differences were found between the two units. The odds of having examination results actually accessed by the ordering physician in an hour or less were 9.5 times greater for the unit with digital viewing capability than for the one without it. PMID- 8439582 TI - Improvement of detection in computed radiography by new single-exposure dual energy subtraction. AB - It is reported that the use of the dual-energy subtraction method enhances the abnormal shadow detection capability. However, because the subtracted image is significantly inferior to the original in signal-to-noise ratio (SNR), the x-ray dosage normally used for chest x-rays has not yielded subtracted images with adequate SNRs. Under these circumstances, we focus on the fact that there is a correlation between the noise contents of bone-and soft-tissue-subtracted images although there is no correlation between the signal contents of these images. We propose an algorithm that improves SNRs of subtraction images by reducing the noise only. PMID- 8439583 TI - Automatic lung nodule detection using profile matching and back-propagation neural network techniques. AB - The potential advantages of using digital techniques instead of film-based radiography have been discussed extensively for the past 10 years. A major future application of digital techniques is computer-assisted diagnosis: the use of computer techniques to assist the radiologist in the diagnostic process. One aspect of this assistance is computer-assisted detection. The detection of small lung nodule has been recognized as a clinically difficult task for many years. Most of the literature has indicated that the rate for finding lung nodules (size range from 3 mm to 15 mm) is only approximately 65%, in those cases in which the undetected nodules could be found retrospectively. In recent published research, image processing techniques, such as thresholding and morphological analysis, have been used to enhance true-positive detection. However, these methods still produce many false-positive detections. We have been investigating the use of neural networks to distinguish true-positives nodule detections among those areas of interest that are generated from a signal enhanced image. The initial results show that the trained neural networks program can increase true-positive detections and moderately reduce the number of false-positive detections. The program reported here can perform three modes of lung nodule detection: thresholding, profile matching analysis, and neural network. This program is fully automatic and has been implemented in a DEC 5000/200 (Digital Equipment Corp, Maynard, MA) workstation. The total processing time for all three methods is less than 35 seconds. In this report, key image processing techniques and neural network for the lung nodule detection are described and the results of this initial study are reported. PMID- 8439584 TI - Communications for a picture archiving communications system with a parallel operating image data base. AB - In cooperation with BAZIS (Support Group Hospital Information Systems at Leiden, The Netherlands), we started the design of a Picture Archiving and Communications System (PACS) a few years ago that contains a centralized image data base. By means of system modeling and measuring some performance parameters, we have discovered that such a system cannot provide the required response times. This is mainly because of equipment communications interfaces that are not fast enough and have a throughput that does not generally exceed 16 Mbits/second. By providing a parallel operating image buffer system, the problems related to the limited speed of the communication interfaces can be overcome. Moreover, by splitting the network into a number of subnets connected to each other by means of "bridges," the communications load can be locally reduced, improving in this manner the response times. Our PACS contains a supervisor and one relational data base that relates patient data with image locations. A significant part of the report is concerned with the design of the high speed American College of Radiology-National Electronic Manufacturing Association transmission control protocol/internet protocol (ACR-NEMA TCP/IP) communications interface. The use of such an interface eliminates the need for a Network Interface Unit, reducing in this manner communication delays and complexity. We have developed and have in operation for experimental purposes a small-scale PACS, consisting of a number of workstations, a relational data base and image buffers, all connected to a network that uses the ACR-NEMA TCP/IP protocols. This experimental PACS is used to provide input data to a PACS performance model, to validate this model, and to investigate alternative system configurations. PMID- 8439586 TI - Fibroblastic cell cycling in collagen gels. AB - Quiescent C3H10T1/2 mouse fibroblasts resume DNA synthesis and proliferation following incubation in medium containing fresh serum both when grown in monolayer and when grown in a collagen matrix. We observed that the rate of DNA synthesis is reduced at high initial cell densities and low initial collagen concentrations. In a collagen matrix, fibroblasts contract the matrix causing an increase in cell density and collagen concentration. We studied the chronological relationship between the kinetics of DNA synthesis and the collagen matrix contraction. The rate of collagen collection per cell changes in time, dependent on initial cell and collagen concentration. The kinetics of the collagen collection showed a positive correlation with the kinetics of DNA synthesis, 16 h later. PMID- 8439585 TI - Humoral stimulating activities in post-cyclophosphamide rat sera and their purified fractions. AB - Enhanced humoral, stimulating activities (HSAs) of post-cyclophosphamide (CY) sera and their purified fractions, acting on mitogen activated T-lymphocytes, were detected in Wistar rats after treatment by high single doses of the aplasia producing alkylating cytostatic drug CY. These activities, monitored in vitro, were partially purified from post-CY sera, collected 2, 4, and 7 days after treatment, yielding fractions with higher humoral stimulating activity. The preliminary purification included molecular cutting by Amicon-Diaflo filters (1 30 kDa pore size range) and gel-filtration on Sephadex G-50 and G-75. Results show that post-CY sera partially purified fraction (10-20 kDa), enhances the proliferation of hydrocortisone resistant (HCR) T-lymphocytes up to threefold under microculture conditions (P << 0.001); partially purified post-CY sera fraction (10-20 kDa) increases the proliferative response of T-cells in microcultures to the mitogenic 145-2C11 monoclonal antibody (mAb) up to tenfold (P << 0.001). These results show that the activity of stimulating factors is localized in the molecular weight range of 10-20 kDa. PMID- 8439587 TI - Cell cycle progression in human cells following re-oxygenation after extreme hypoxia: consequences concerning initiation of DNA synthesis. AB - The initiation of DNA synthesis and further cell cycle progression in cells during and following exposure to extremely hypoxic conditions in either G1 or G2 + M has been studied in human NHIK 3025 cells. Populations of cells, synchronized by mitotic selection, were rendered extremely hypoxic (< 4 p.p.m. O2) for up to 24 h. Cell cycle progression was studied from flow cytometric DNA recordings. No accumulation of DNA was found to take place during extreme hypoxia. Cells initially in G1 at the onset of treatment did not enter S during up to 24 h exposure to extreme hypoxia, but started DNA synthesis in a highly synchronous manner within 1.5 to 2.25 h after reoxygenation. The duration of S phase was only slightly affected (increased by approximately 10%) by the hypoxic treatment. This suggests that the DNA synthesizing machinery either remains intact during hypoxia or is rapidly restored after reoxygenation. Cells initially in G2 at the onset of hypoxia were able to complete mitosis, but further cell cycle progression was blocked in the subsequent G1. Following reoxygenation, these cells progressed into S phase, but the initiation of DNA synthesis was delayed for a period corresponding to at least the duration of normal G1 and did not appear in a synchronous manner. In fact, cell cycle variability was found to be increased rather than decreased as a result of exposure to hypoxia starting in G2. We interpret these findings as an indication that important steps in the preparation for initiation of DNA synthesis take place before mitosis. Furthermore, the change in cell cycle duration induced by hypoxia commencing in G1 is of a nature other than that induced by hypoxia commencing in other parts of the cell cycle. PMID- 8439588 TI - The influence of cell co-operation, nutrients and surface area on cell division. AB - Two opposite views have been proposed to explain the decline of the growth potential in cell populations with a limited life span: 1 variations in the probability of cycling and in cycling times or 2 a progressive increase in the nondividing cell fraction. Human brain-derived cells were studied with respect to their proliferative potential under the influence of different growth conditions, using haptotactic palladium islands on agarose. The results emphasize the need for cell co-operation, surface area and nutrients for cell division. These parameters also influence the final cell density. The results illustrate the multiple factors that can vary the probability of initiating the division cycle and stress the uncertainty of defining the irreversible non-dividing state. PMID- 8439589 TI - Inhibition of distinct steps in the adipocyte differentiation pathway in 3T3 T mesenchymal stem cells by dimethyl sulphoxide (DMSO). AB - The process of adipocyte differentiation in murine 3T3 T mesenchymal stem cells involves three well-defined steps: 1 predifferentiation growth arrest; 2 non terminal (reversible) differentiation and 3 terminal differentiation associated with the irreversible loss of proliferative potential. To further investigate these processes, the effects of dimethyl sulphoxide (DMSO), an agent that affects differentiation in several other cell systems, was tested. The results show that DMSO modulates two distinct steps of adipocyte differentiation. The first effect is evident when growing 3T3 T cells are cultured in differentiation-inducing medium in the presence of DMSO. Therein the expression of adipocyte phenotype is inhibited because the cells fail to growth-arrest at the predifferentiation growth arrest state. Instead in the presence of DMSO, cells growth-arrest at a biological state that does not support differentiation. The second effect is evident if nonterminally differentiated adipocytes are cultured in terminal differentiation-inducing medium containing DMSO. Therein the terminal step in differentiation is inhibited. These inhibitory effects occur in a dosage dependent manner; maximum inhibition of differentiation requires 2% DMSO. Therefore, whereas DMSO typically promotes differentiation in other cell systems, DMSO inhibits multiple steps in the process of adipocyte differentiation. These observations support the conclusion that a single pharmacological agent can have markedly different effects on specific cell types. Even more important, the data establish that DMSO can now be used as a tool to study the molecular mechanisms involved in the multistep process of adipocyte differentiation. PMID- 8439591 TI - The in vitro response of human tumour cells to desferrioxamine is growth medium dependent. AB - Iron chelating agents have been demonstrated to inhibit tumour cell growth. However, in vitro and in vivo results using desferrioxamine a hexadentate iron chelating agent, for anti-cancer treatment are not always in agreement. Therefore, we have studied the response of three human tumour cell lines (HL-60 promyelocytic leukaemia, MCF-7 breast cancer and HepG2 hepatoma), grown in culture medium supplemented with either human pooled (HPS) or fetal bovine serum (FBS), to desferrioxamine. Desferrioxamine, at micromolar concentrations, induced severe cytotoxicity in all tumour cell lines grown in FBS medium. When grown in HPS medium, comparable desferrioxamine cytotoxicity was observed in the millimolar range. The addition of 50% saturated human transferrin to FBS medium resulted in protection against desferrioxamine cytotoxicity. HL-60 cells were further studied for iron metabolism characteristics. HL-60 cells, grown in medium with FBS, were found to have an 8.4 fold increase in surface transferrin receptor (TfR) expression (P < 0.001) as compared with HL-60 cells grown in medium with HPS. However, iron uptake of HPS cultured HL-60 cells, after incubation with saturated human transferrin, was higher, resulting in a higher concentration of iron in HPS cultured HL-60 cells as compared with FBS cultured cells (1.72 +/- 0.02 mumol/g protein v. 1.32 +/- 0.14 mumol/g protein; P < 0.001). Using desferrioxamine it was shown that TfR expression is dependent on the biological availability of iron in the cell. Consistent with the lower iron content in FBS cultured cells, we conclude that the cytotoxicity of desferrioxamine is dependent on the ability of cells to replenish cellular iron stores from the culture medium. Cells grown in FBS medium lack this ability and are therefore more susceptible to desferrioxamine. PMID- 8439590 TI - Ki-67 expression and BrdUrd incorporation as markers of proliferative activity in human prostate tumour models. AB - The validity of the use of the monoclonal antibodies Ki-67 and anti-BrdUrd to evaluate proliferative activity of human prostate tumour models was studied. Growth of the transplantable PC-82 and PC-EW prostate tumours, as assessed by tumour volume measurements, was significantly correlated with the proliferative activity as reflected by BrdUrd incorporation into DNA (r = 0.64 and r = 0.78, respectively). The proliferative activity of PC-82 tumours detected by Ki-67 antigen expression paralleled the pattern observed with BrdUrd (r = 0.51) and a significant correlation (r = 0.60) between the results obtained with both markers was found. In growing PC-82 and PC-EW tumours only small variations in the Ki-67 and BrdUrd indices were observed. In contrast, Ki-67 expression in regressing PC 82 tumours varied considerably (2.7 +/- 2.2%). The BrdUrd index in regressing PC 82 tumours showed less variation (1.3 +/- 0.2%), but part of the BrdUrd-positive cells were found in the stromal (murine) part of the regressing tissue. It is concluded that the Ki-67 and BrdUrd proliferation markers are reliable parameters to monitor changes in growth of prostate tumour lines, but that in slow growing or regressing tumours Ki-67 and BrdUrd data should be interpreted with caution. PMID- 8439592 TI - An immunoblotting procedure following agarose gel electrophoresis for subclass typing of IgG paraproteins in human sera. AB - A method for subclass typing of IgG paraproteins in human sera following agarose gel electrophoresis is presented. After electrophoretic separation, serum proteins were blotted by capillary diffusion onto nitrocellulose. Mouse anti human IgG1-IgG4 monoclonal antibodies were exposed to bound IgG. Goat anti-mouse IgG alkaline phosphatase conjugate was employed as second antibody. Thirty six sera were examined, in which the presence of an IgG paraprotein had previously been proved by agarose gel electrophoresis and subsequent immunofixation with anti-IgG antiserum. The subclass frequency distribution was 27 IgG1, 6 IgG2, 2 IgG3 and 1 IgG4. By means of IgG subclass typing in 8 out of these 36 sera, a total of 12 additional monoclonal bands (1 to 2 bands per serum) were detected which were not seen after immunofixation electrophoresis with anti-IgG antiserum. Eleven of 12 additional bands belonged to an IgG subclass different from that of the bands already detected by immunofixation electrophoresis. Light chain typing was performed in 9 of 12 bands found additionally. Two of these 9 bands belonged to a light chain class different from that of the bands already detected by immunofixation electrophoresis. The method described can be employed to further elucidate the possible diagnostic and prognostic significance of the subclass type of an IgG paraprotein. PMID- 8439593 TI - Pre-analytical, analytical and biological sources of variation of lipoprotein(a). AB - The pre-analytical, analytical and biological sources of variation were estimated for serum lipoprotein(a) concentrations, as measured with a new commercially available procedure. There were no significant differences between the concentrations of lipoprotein(a) measured in EDTA plasma and serum. The analyte is stable in specimens stored for up to two weeks in the refrigerator, or up to three months at-20 degrees C. Fasting is not essential before the lipoprotein(a) determination. Data on analytical (between-run coefficient of variation < 15.7%), within-subject (8.6%) and between-subject variation (85.8%) were used to calculate the analytical goal for imprecision (< 4.3%), the critical difference between serial values from an individual that represents a significant change (36.3%), the number of specimens which should be collected to estimate the homeostatic value for an individual to within +/- 5% (26), and to establish the marked individuality of lipoprotein(a) (index of individuality, 0.1). PMID- 8439594 TI - New approaches with the Chem-1 creatinine determination. AB - Three modifications of the Chem-1 determination of serum creatinine were tested. Two different algorithms developed for compensating the interference of bilirubin were compared with the current one by analysing bilirubin-enriched albumin solutions and 82 icteric serum samples. A number of known other interfering substances were also tested. The modification involving parallel bichromatic measurement plus bilirubin correction appeared to give the best performance. However, despite the improvements, the determination is not yet completely satisfactory. PMID- 8439595 TI - Reference ranges for thyrotropin in the serum of full-term neonates--compared with the ranges for full-term neonates with various post-partal adaptation disorders, and premature neonates. AB - The "IMx hTSH ultrasensitive test" from Abbott Laboratories is a new method for the determination of thyrotropin. Its introduction for the purpose of hypothyreosis screening led to the present investigation of the reference ranges in full-term and premature neonates. In a total of 1712 healthy neonates, the reference range for serum thyrotropin on the 5th day post partum was 0.4-9.05 mU/l (median value 1.90 mU/l). In contrast, 64 full-term neonates with various post-partal adaptation disorders showed a significantly lower serum thyrotropin concentration on the 5th day post partum (0.14-6.39 mU/l; median value 1.60 mU/l). Serum thyrotropin was also determined on the 7th and 14th day post partum in 131 premature neonates with birth-weights below 2500 g. In the birth-weight range 1500- < 2500 g, the median values for serum thyrotropin were 2.35 and 2.12 mU/l, respectively. A negative correlation (r = -0.3019) was found between the birth-weight and the serum thyrotropin concentration on the 14th day post partum. In two premature neonates with birth-weights less than 800 g, the serum thyrotropin concentrations were conspicuously high (18.6 and 28.0 mU/l) on the 14th day post partum. PMID- 8439596 TI - Immunonephelometry and radial immunodiffusion compared for measuring serum retinol-binding protein. AB - We compared a nephelometric method and a radial immunodiffusion (RID) assay for the measurement of retinol-binding protein in samples of serum from children with malignancies. The mean (+/- standard deviation) retinol-binding protein concentration as measured by the Behring Nephelometer was 31.0 +/- 15.6 mg/l; the mean by RID was 31.2 +/- 15.7 mg/l. This difference was not statistically significant by Student's t test (P = 0.6), and the correlation coefficient (r) was 0.87. Thus, the Behring Nephelometer method measures retinol-binding protein rapidly and as accurately as radial immunodiffusion. PMID- 8439597 TI - New neonatal thyrotropin enzyme immunoassay with fluorimetric detection: comparison with time-resolved fluoroimmunoassay. AB - This short communication compares a novel fluorimetric microplate enzyme immunoassay (FEIA) with a commercial time-resolved fluoroimmunoassay for the determination of thyrotropin in dried blood spots. The evaluation was performed using a retrospective study design with newborn blood samples from three screening centres. Non-parametric Spearman rank correlation analysis revealed highly significant positive correlation between methods: rs = 0.465, p < 0.0001 (Hannover), rs = 0.659, p < 0.0001 (Minsk), rs = 0.755, p < 0.0001 (Helsinki). Wilcoxon signed rank test performed for paired FEIA and time-resolved fluoroimmunoassay showed that the results obtained by both tests represented the same distribution (p < 0.0001). The new method, using fluorimetric detection, can be performed with the instrumentation commonly used for the screening of congenital hypothyroidism and phenylketonuria. Results are obtained within three to four hours after arrival of the sample in the laboratory. Preliminary evaluation indicates the method to be a suitable alternative to time-resolved fluoroimmunoassay for neonatal thyroid function screening. PMID- 8439598 TI - Zero-adjustment of Eppendorf flame photometers for lithium measurement is incorrect. PMID- 8439599 TI - Spectral analysis of the EEG and 99m-Tc-HMPAO SPECT-scan in Alzheimer's disease. AB - 99m-technetium-hexamethylpropylene-amineoxine (99m-Tc-HMPAO) single-photon emission-computer-tomography (SPECT)-scans and spectral analyzed electroencephalogram (EEGs) of 20 patients with Alzheimer's disease (AD) were studied. A significant correlation was found between the temporoparietal cerebellar-ratio (TP/C-ratio) of the SPECT-scan and the peak frequencies of leads T3-T5, C3-P3, and C4-P4 of the EEG. In addition a significant negative correlation between the TP/C-ratio and the theta/alpha-ratio (t/a-ratio) of leads T3-T5, T4-T6, C3-P3, and C4-P4 was demonstrated. Our study demonstrates that slowing of the EEG parallels a decrease in blood flow in the temporoparietal regions in AD-patients. Both findings could be parallel phenomena of regional hypometabolism. PMID- 8439600 TI - The effects of antidepressants on the thyroid axis in depression. AB - Thirty-nine patients with major depression were studied to determine the differential effects of desipramine (DMI) and fluoxetine (FLU) on thyroid hormones. Twenty-six percent showed some abnormality in baseline thyroid hormone levels. There were no demonstrable differences for any of the thyroid indices from baseline to the 3- or 6-week samples for the total group or for either drug by repeated measures analysis of variance. There was a significant group by time interaction for total thyroxine (TT4) between the drug treatment groups, which was caused by a small but significant increase in TT4 in the DMI sample. Correlations were performed between the change in hormones over the 6 week period and treatment response. There was a significant association between a decline in triiodothyronine (T3) levels and response to FLU but not DMI. The implications of these findings for the pathophysiology of depression and antidepressant drug mechanisms are discussed. PMID- 8439601 TI - Psychophysiologic assessment of attempts to simulate posttraumatic stress disorder. PMID- 8439602 TI - Disruption of sensory gating by the alpha 2 selective noradrenergic antagonist yohimbine. PMID- 8439603 TI - The interface between thyroid activity, magnesium, and depression: a pilot study. PMID- 8439604 TI - CSF corticotropin-releasing factor is not affected in panic disorder. PMID- 8439605 TI - Exercise-induced "arterialization" of venous blood in some schizophrenics: a further note on possible microcirculation disturbances. PMID- 8439606 TI - The possible association between affective disorder and partially deleted mitochondrial DNA. PMID- 8439607 TI - IL-1b and Kallmann's syndrome: a variant model of schizophrenia? PMID- 8439608 TI - Metabolic subtypes in patients with schizophrenia. AB - Patterns of regional cerebral glucose metabolism were examined in a group of patients with schizophrenia (n = 17) and normal controls (n = 16) to determine if different metabolic profiles were present. For the patients with schizophrenia, two profiles were found. The first was characterized by a normal "shape" but overall reductions in cerebral metabolism. The second had focal reductions in frontal metabolism. This latter group also had significantly larger frontal horns than the other schizophrenic group. The two groups with schizophrenia did not differ on other attributes or clinical variables. These results are discussed in terms of our understanding of heterogeneity in schizophrenia and etiology. PMID- 8439609 TI - Lateralized attentional abnormality in schizophrenia is correlated with severity of symptoms. AB - Numerous studies have demonstrated a lateralized impairment of attention in schizophrenia. In this study, attention in schizophrenia is investigated with a task that involves centering a rod while blindfolded. Symptoms were rated on the Brief Psychiatric Rating Scale (BPRS) for each of the 20 schizophrenic subjects. The more symptomatic patients demonstrated a right-sided hemineglect compared to the less symptomatic patients (p = 0.013). Furthermore, the difference between more and less symptomatic patients was even more distinct when they were categorized by the BPRS schizophrenia subscale alone (p = 0.0025). These findings support the hypothesis that the pathophysiology of schizophrenia involves a lateralized defect in the control of attention, and that this defect is associated with the severity of symptoms. This raises the possibility that effects of neuroleptic medication may be asymmetric, which could account for some of the inconsistencies in studies of hemispheric dysfunction in schizophrenia. PMID- 8439610 TI - Round spermatid nuclei injected into hamster oocytes from pronuclei and participate in syngamy. AB - Round spermatids are spermatogenic cells that have just completed meiosis. To discover whether nuclei of these haploid cells are genetically ready for fertilization, nuclei were individually injected into mature hamster oocytes via a microsurgical technique. In the majority of oocytes that were successfully injected and activated, spermatid nuclei transformed into pronuclei and underwent DNA synthesis. Ultimately their chromosomes mingled with ootid chromosomes immediately prior to the first cleavage. Although we could not determine the developmental potential of these zygotes, spermatid nuclei appear capable of participating in syngamy. PMID- 8439611 TI - Ontogenesis of 3 beta-hydroxysteroid dehydrogenase delta 5-delta 4 isomerase in the rat ovary as studied by immunocytochemistry and in situ hybridization. AB - The enzyme complex 3 beta-hydroxy-5-ene-steroid dehydrogenase and steroid 5-4-ene isomerase (3 beta-HSD) is involved in the biosynthesis of all classes of active steroids, namely glucocorticoids, mineralocorticoids, and sex steroids. To obtain more information about the age-specific expression and localization of 3 beta-HSD during development in the rat ovary, two complementary cytochemical techniques were used, immunocytochemical localization with antibodies against purified human placental 3 beta-HSD, and 3 beta-HSD mRNA localization achieved by in situ hybridization with a [35S]-labeled cDNA encoding 3 beta-HSD. In the fetal ovary, no significant immunolabeling or hybridization signal could be observed. The first expression of the enzyme was observed 6 days after birth, immunolabeling as well as autoradiographic reaction being found in a few interstitial gland cells. At the 10th day of postnatal life, the theca interna cells of growing follicles appeared to be labeled with both techniques. The granulosa cells of growing follicles also exhibited hybridization signal, whereas no immunostaining could be detected in these cells at any of the time intervals studied. At puberty, 3 beta HSD was localized in theca interna and granulosa cells of the growing and mature follicles as well as in the interstitial gland and corpus luteum cells. Similar results were obtained in 40-day-old and adult animals. The present data indicate a progressive expression of 3 beta-HSD in different morphological structures during ovarian development in the rat. PMID- 8439612 TI - Endogenous retinoids in rat epididymal tissue and rat and human spermatozoa. AB - Recent work has demonstrated high levels of retinoid binding proteins in rat epididymis, and a lumenal retinoic acid binding protein has been purified. These findings suggested that vitamin A may be involved in spermatozoal maturation in the epididymis. We further addressed this question by quantifying retinol, retinyl esters, and retinoic acid isomers from perfused epididymal tissue, from rat testicular and epididymal spermatozoa, and from human ejaculate sperm. HPLC showed vitamin A levels to be higher in caput than in corpus or cauda tissue. Retinoic acid and 9-cis-retinoic acid were found to be graded from lowest levels in caput to highest in cauda. Spermatozoa from caput epididymidis and enriched testicular spermatozoa were found to have higher levels of vitamin A than did spermatozoa from corpus or cauda epididymidis. Spermatozoal retinyl esters had acyl substituents similar to those seen in whole epididymis, and diminished in quantity in sperm from distal segments. Human ejaculate sperm were found to retain high levels of retinyl palmitate and stearate. Retinol and retinoic acid were only marginally detectable in human sperm. Retention of retinoids in mature spermatozoa suggests roles for vitamin A in spermatozoal reproductive physiology beyond the epididymal stage. PMID- 8439613 TI - DNA synthesis occurs throughout the rat ventral prostate during its postnatal development. AB - We previously used autoradiographic methods to show that cells proliferate throughout the rat ventral prostate during its postnatal development (Biol Reprod 1991; 45:773-782). The objective of the present study was to quantify the extent to which DNA synthesis, and thus growth, occur in the distal and proximal segments of the rat ventral prostate. To this end, rats were administered 3H thymidine in vivo. Subsequently, 3H-thymidine incorporation per prostatic segment and per micrograms DNA was determined, as was the number of labeled cells in the proximal and distal segments. We report that 3H-thymidine was incorporated into both the distal and proximal segments of the ventral prostate of rats 10, 20, 45, and 60 days of age, with significantly greater amounts (6-21 times) incorporated into the distal segment at each age. Consistent with this, the distal segment contained 5-20 times more labeled cells than the proximal segment. However, when 3H-thymidine incorporation was expressed per micrograms DNA, only relatively small, though significant, differences were seen between the distal and proximal segments of Days 10 and 20; and no differences were seen at Days 45 and 60. Taken together, these results strongly support the contention that DNA synthesis occurs throughout the rat ventral prostate, and suggests therefore that prostatic growth is not limited to the distal tips of the gland. PMID- 8439614 TI - Insulin-like growth factor (IGF)-I stimulates proliferation and migration of mouse ectoplacental cone cells, while IGF-II transforms them into trophoblastic giant cells in vitro. AB - We examined the effects of a 10.5-day placental extract and various growth factors (insulin-like growth factor [IGF]-1, IGF-II, epidermal growth factor [EGF], basic fibroblast growth factor [b-FGF], and transforming growth factor alpha [TGF-alpha]) on proliferation, migration, and transformation of mouse ectoplacental cone (EPC) cells in vitro. Both the 10.5-day placental extract and IGF-I increased the surface area of the EPC cell colony and strongly stimulated the uptake of bromodeoxyuridine (Brd-U) as well as the migratory activity of EPC cells on the plastic culture dish. Such effects of 10.5-day placental extract were partly inhibited by the addiction of anti-IGF-I antibody. On the other hand, IGF-II did not significantly affect proliferation and migration of EPC cells, but increased the number of cells having a large nucleus (trophoblastic giant cells; TGCs) per EPC and enlarged the ploidy levels of EPC cells. Histochemical staining with succinyl wheat germ agglutinin (s-WGA), an in situ marker for secondary TGCs on Day 10.5 post coitum revealed that IGF-II or the placental extract induced the expression of s-WGA-binding glycoproteins in the TGCs in vitro. The effects of IGF-II or placental extracts were also inhibited by anti-IGF-II monoclonal antibody. No appreciable effect was found in the EPCs cultured with TGF-alpha, whereas b-FGF and EGF promoted migratory activity of the cells. The present study indicates that IGFs or IGF-like substances may be present in the mouse placenta, that IGF-I may promote the proliferation and migration of EPC cells, and that IGF II may induce the transformation of EPC cells into TGCs in vitro. PMID- 8439615 TI - Characterization of a source and levels of plasma immunoreactive inhibin during the ovulatory cycle of the domestic hen. AB - The domestic hen with its well-organized follicular hierarchy offers a unique model system for the study of the role of inhibin in follicular development. We have validated a homologous bovine RIA for use in the hen to measure plasma immunoreactive inhibin-like activity during the ovulatory cycle as well as during experimental conditions in which follicular development has been altered. Validation of the bovine RIA kit revealed that increasing amounts of hen plasma gave linear increases in the amount of immunoreactive inhibin detected. This assay system as well as a homologous chicken LH RIA were used to assess plasma concentrations of immunoreactive inhibin and LH, respectively, in experiments 1 3. In experiment 1, blood samples were collected from hens (n = 5) at 2-h intervals for 24 h starting at 1600 h after the lay of the last egg of the sequence through the following day. No significant peak in plasma immunoreactive inhibin level was detected during the ovulatory cycle, in spite of a significant preovulatory rise in plasma LH. The highest level of plasma immunoreactive inhibin was attained, however, 2 h prior to the preovulatory LH surge. In experiment 2, eCG (n = 6) or vehicle (n = 3) was administered to hens daily for 6 days. A blood sample was drawn immediately before injection each day as well as 24 h after the last day of treatment. Treatment with eCG significantly (p < 0.01) raised plasma immunoreactive inhibin-like levels, compared to vehicle-injected controls. In experiment 3, three to four of the largest follicles (F1-F4) were surgically removed, or sham surgery was performed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8439616 TI - Relationships between the level of atresia and inhibin contents (alpha subunit and alpha-beta dimer) in morphologically dominant follicles during their growing and regressing phases of development in cattle. AB - The objectives were to determine the relationships between changes in the levels of histological and biochemical (estradiol [E2]:androstenedione [A], E2:A ratio) atresia and changes in inhibin contents of morphologically dominant follicles collected during the growing or the regressing phase of the first wave of follicular development in cycling crossbred beef heifers. Heifers were slaughtered either when the dominant follicle (> or = 9 mm; diameter of the antral cavity as assessed by ultrasonography) of the first wave was still growing (n = 7) or when the first dominant follicle (> or = 9 mm; n = 7) was regressing or was at the end of the plateau phase. Following ovary collection, the dominant follicle was dissected and level of histological atresia was determined on sections of follicular walls. Aliquots of follicular fluid from each of the dominant follicles were collected to measure concentrations of E2, A, and inhibin alpha subunit by RIA and to measure concentrations of dimeric (alpha-beta dimer) inhibin by a two-site immunoradiometric assay. Heifers were slaughtered on Days 5.4 +/- 0.5 (growing phase) and 11.8 +/- 0.5 (regressing phase) of the estrous cycle, and mean diameter of the dominant follicles was similar in both phases (9.9 +/- 0.4 vs. 10.8 +/- 0.4 mm; p > 0.09). All morphologically dominant follicles collected during the growing phase (7/7) were histologically healthy and estrogen-active (E2:A ratio > 1), while those collected during the regressing phase (7/7) were histologically atretic and estrogen-inactive (E2:A ratio < 1; chi 2 = 14.0, p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8439617 TI - Localization of leukocyte subsets in the rat ovary during the periovulatory period. AB - The ovulatory process has been compared with inflammation because several classical inflammatory mediators appear to participate in this process. One component of the inflammatory reaction is the migration of leukocytes to the site of inflammation and the subsequent activation of these cells. We have reported recently that perfusion of leukocytes into the rat ovary in vitro enhances the number of LH-induced ovulations, which suggests an active role of leukocytes in ovulation. In the present study we characterize immunohistochemically the distribution of macrophages, T lymphocytes, and granulocytes in the ovaries of untreated immature rats and of eCG-hCG-primed rats killed prior to hCG injection, at ovulation, and at 33-36 h post-ovulation. Macrophages, identified with monoclonal antibodies ED1 and ED2, were the major leukocyte population and were found primarily in the medullary region surrounding the blood vessels. The density of the cells in this region increased continuously during development to sexual maturity and until after ovulation. Macrophages were also present in the thecal layer of the preovulatory follicles, and the numbers of these cells increased about 5-fold in this area in ovulating follicles (12 h after hCG) compared to preovulatory follicles (before hCG). A portion of macrophages in both areas expressed major histocompatibility complex (MHC) class II antigens (OX6+); these cells were present mostly in the medullary region, with no apparent change in density during the periovulatory period. Neutrophilic granulocytes comprised a lesser proportion of the total leukocyte population in the medullary region but were abundant in the thecal layer. The density of neutrophils increased 3-fold in the medullary region and 8-fold in the thecal region in ovulatory compared to preovulatory follicles. T lymphocytes (OX52+) were evenly distributed at relatively low density in the medulla and the stroma of the cortex. Most T lymphocytes expressed the CD8 antigen (OX8+) and hence were of the MHC class I restricted phenotype. Few T lymphocytes were present in the thecal layer. In summary, macrophages, neutrophilic granulocytes, and T lymphocytes are present in the ovary at ovulation. There is a selective increase in the numbers of macrophages and neutrophilic granulocytes in the medullary region and in the thecal layer as the ovulatory period progresses, indicating that these cells may actively be involved in the tissue remodeling occurring at ovulation. PMID- 8439618 TI - Extracellular matrix composition and resilience: two parameters that influence the in vitro migration and morphology of rat inner cell mass-derived cells. AB - Parietal endodermal (PE) migration along rat trophectodermal (TE) cells coincides with the deposition of Reichert's membrane between these two cell layers. In this study, we compared the influences of fibronectin and laminin, two components of Reichert's membrane, on the migration and replication of PE-like cells from cultured rat inner cell masses (ICMs). We also explored the role of substrate nondeformability by comparing cell translocation on gels versus coatings of Matrigel (a tumor cell-derived basement membrane preparation) or of collagen. ICMs, isolated by immunosurgery from Day 5 blastocysts, were cultured on coatings of collagen IV, laminin, fibronectin, collagen I, or Matrigel, or on gels of the latter two substrates. Minimal laminin or fibronectin coating concentrations of 2.5 micrograms/ml were required for ICM attachment and cell migration. Migration was similar during the first 48 h of culture on fibronectin and on laminin; however, by 72 h, the extent of cell translocation on fibronectin was greater (1.5- to 2-fold) than that measured on laminin. Fibronectin-cultured ICM-derived cell clusters also contained 1.5- to 2-fold more cells than those on laminin. Migration did not occur on undiluted gels of Matrigel but was supported by diluted (1:10 and 1:20) Matrigel coatings. Similarly, cell migration on coatings of collagen IV reached almost 3-fold that measured on collagen I gels. Most of the cells migrating on fibronectin or collagen (I or IV) were flattened and elongated. In contrast, a high proportion of the cells migrating on laminin or Matrigel coatings were tall and rounded, with thin cytoplasmic extensions. Fibronectin- and collagen IV-cultured cells stained strongly for both collagen IV and laminin, but contained no fibronectin. In contrast, laminin-cultured cells contained fibronectin but were less immunoreactive for laminin and collagen IV. These findings indicate that substrate composition and resilience influence the in vitro migration and morphology of ICM-derived PE-like cells. A role for the TE cells in anchoring Reichert's membrane during development of the PE cell layer within the blastocyst is postulated. Furthermore, the sensitivity of cell morphology and differentiation to individual basement membrane components provides a potential key mechanism whereby an emerging basement membrane can regulate cell migration and differentiation, two fundamental processes that occur throughout embryonic development. PMID- 8439619 TI - Modulation of the fertilizing ability of spermatozoa from roosters carrying the Sd (sperm degeneration) allele. AB - Roosters carrying the Sd (sperm degeneration) allele produce spermatozoa that die prematurely in vivo. Consequently, these mutants are subfertile. The objective of the present study was to determine whether or not subfertility could be modulated. A previous study found that the proximal efferent ducts of mutants were characterized by a reduced surface-to-volume ratio. We hypothesized that if subfertility was exacerbated by hemicastration of chicks, which increases daily sperm production in adults, then a relationship between efferent duct function and sperm longevity would be likely. In experiment 1, hemicastration of chicks exacerbated the subfertility of adults (p < 0.001). As inferred from SDS-PAGE in previous research, mutants lack at least one non-albumin seminal plasma protein. Therefore, it was hypothesized that protein supplementation would ameliorate subfertility. In experiment 2, fertility increased (p < 0.001) when spermatozoa from mutants were mixed with albumin-depleted seminal plasma protein from fertile roosters before insemination. In contrast, supplementation with BSA had no effect (p > 0.05). In summary, the subfertile status of Sd roosters was dynamic and appeared to depend upon the interaction of testicular output, efferent duct structure, and seminal plasma protein. Thus the study of this dysfunction may help to identify factors responsible for sperm maturation in the domestic fowl. PMID- 8439620 TI - Immunocytochemical localization and endogenous synthesis of apolipoprotein E in testicular Leydig cells. AB - Apolipoprotein E (apoE) is synthesized by a wide variety of tissues, including those involved in steroidogenesis; its function in most extrahepatic tissues is unknown. Significant amounts of apoE mRNA have been detected in the testis, but the cellular origin of this material has not yet been determined. The purpose of the present study was to determine whether the steroidogenic cells of the testis synthesize apoE. We localized apoE in the testis of mice by an avidin-biotin peroxidase technique using a cross-reactive anti-rat apoE antibody. ApoE immunoreactivity was strongest in interstitial cells but was also diffusely localized throughout the seminiferous tubules. Acute treatment of mice with hCG diminished apoE immunoreactivity in the testis. A murine Leydig tumor cell line (I-10 cells) also demonstrated apoE immunoreactivity, suggesting that at least one source of interstitial apoE is the Leydig cell. Normal Leydig cells were subsequently isolated from control and hCG-treated mice using Percoll density gradients. Isolated hepatocytes, I-10 cells, and Leydig cells (with or without hCG in vitro) were incubated in the presence of [35S]methionine. A 35S-labeled protein of approximately 33-35 kDa was immunoprecipitated from the cells and media of all three types of preparations using whole antiserum or affinity purified antibody. Preincubating the antibodies with apoE-containing murine very low-density lipoprotein or purified rat apoE eliminated these bands. Leydig cell apoE synthesis and secretion were decreased by hCG treatment in vivo and/or in vitro. These data suggest that apoE is synthesized by normal and transformed Leydig cells and may play a role in sterol transport in the testis. PMID- 8439621 TI - A factor(s) from a rat trophoblast cell line inhibits prolactin secretion in vitro and in vivo. AB - The purpose of the present study was to measure the inhibitory action of secretions from trophoblast cells on prolactin (PRL) secretion in cycling and pregnant rats, and to determine whether factor(s) from trophoblast cells act directly on anterior pituitary cells. A rat choriocarcinoma cell line (Rcho)--a line consisting of trophoblast cells, including differentiated giant cells that secrete members of the placental PRL family--was used. When Rcho cells (1 x 10(6) cells) were transplanted under the kidney capsule of cycling rats, tumors developed and the rats went into constant diestrus. Eight days after cell injection, plasma progesterone was significantly increased in treated rats compared to controls, whereas plasma and pituitary PRL and pituitary PRL mRNA levels were significantly decreased. Similar PRL results were seen on Day 9 of pregnancy after injection of Rcho cells on Day 0 or Day 1 of pregnancy. To determine whether secretions from Rcho cells had a direct effect on anterior pituitary cells to inhibit PRL release, anterior pituitary cells were enzymatically dispersed and cultured for 4 days. Conditioned medium was obtained from 9-day Rcho cell cultures and concentrated by ultrafiltration. A fraction containing substances with molecular weights greater than 10,000 suppressed PRL release from the pituitary culture after 3 and 24 h. Conditioned medium containing substances with molecular weights between 1000 and 10,000 had no effect on PRL release, nor did conditioned medium from a placental cell line designated HRP-1. HRP-1 also contains trophoblast cells but does not contain the differentiated giant cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8439623 TI - Inhibition of acrosin activity with a trypsin inhibitor blocks human sperm penetration of the zona pellucida. AB - To evaluate the role of acrosin in human sperm penetration of the zona pellucida (ZP), sperm-oocyte interaction was studied after acrosin activity was blocked with soybean trypsin inhibitor (SBTI). Oocytes that had failed to fertilize because of sperm pathology in a clinical in vitro fertilization program were used to assess sperm binding to and penetration into the ZP. The acrosome reaction of sperm bound to the ZP was determined using fluorescein-labeled Pisum sativum agglutinin after sperm were removed from the ZP. Acrosin activity, determined by a gelatin substrate film method, was severely inhibited by 2 mg/ml SBTI. Sperm motility and movement characteristics, assessed by a Hamilton-Thorn motility analyzer, were unchanged after 6-h incubation with SBTI. Inhibition of acrosin activity did not affect the number of sperm bound to the ZP but completely blocked sperm penetration of the ZP after a 5-h incubation. SBTI did not influence the spontaneous acrosome loss of sperm in culture medium after 6-h and 20-h incubations, but the percentage of acrosome-reacted sperm bound to the ZP was significantly reduced. It was concluded that acrosin activity plays a key role in sperm-zona interaction in humans. Motile sperm are unable to penetrate the ZP when acrosin activity is inhibited. This might result from interference with a phase of the sperm-ZP binding reaction or with a lytic action of acrosin. Also, acrosin may be involved in the acrosome reaction induced by sperm binding to the ZP. PMID- 8439622 TI - Apparent absence of negative feedback in middle-aged persistent-estrous rats following luteinizing hormone-releasing hormone agonist treatment: relation to plasma inhibin and 17 beta-estradiol. AB - Reproductive aging in female rats is associated with a transition from regular estrous cyclicity to an anovulatory condition described as persistent estrous (PE). This PE condition is characterized by continued follicular development with elevated circulating levels of estrogen and FSH. In an attempt to investigate further the age-related changes in neuroendocrine function of PE rats, we have developed a model through which the return of hypothalamic-pituitary and ovarian function can be assessed following the withdrawal of chronic LHRH agonist suppression. Subsequent to withdrawal of continuous (2.5 micrograms/h for 12 days) LHRH agonist [DTrp6, Pro9-NHEt]-LHRH (LHRH-AG) treatment, circulating FSH concentrations in PE rats increase and remain elevated with an apparent absence of ovarian negative feedback, and these rats fail to return to estrous cyclicity. In the present studies, estrogen administration induced significant decreases in FSH secretion in PE rats following withdrawal of LHRH-AG treatment and ovariectomy (OVX), suggesting that the negative feedback response to estrogen is maintained in PE females. However, progesterone administration 2 days later failed to elicit a positive feedback response of gonadotropin secretion in PE females prior to LHRH-AG treatment, serum inhibin and 17 beta-estradiol (E2) concentrations were similar in middle-aged PE rats and young cyclic females on proestrus, while FSH levels were significantly greater in PE rats. After withdrawal of LHRH-AG treatment, plasma FSH concentrations remained elevated in PE rats as compared to young rats despite similar increases in E2. However, increases in plasma inhibin were delayed and significantly attenuated in PE rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8439624 TI - Chromatin configurations and meiotic competence of oocytes are related to follicular diameter in nonstimulated rhesus monkeys. AB - Specific aims of this study were to compare relationships between size of intact antral follicles and meiotic competence, diameters, and chromatin configurations of germinal vesicle (GV) oocytes in non-gonadotropin-stimulated rhesus monkeys. Intact antral follicles were dissected from excised ovaries of nine normally cycling monkeys in the follicular phase of the menstrual cycle and of two acyclic monkeys. Follicles were classified according to diameter: I (200-450 microns), II (451-700 microns), III (701-1000 microns) and IV (> 1000 microns). Cumulus enclosed oocytes were released from follicles and either measured (diameter) and fixed immediately or cultured for 48 h in modified CMRL medium containing 0.5 micrograms/ml ovine FSH, 10 micrograms/ml ovine LH, and 10% bovine calf serum. Following Hoechst staining, three distinct patterns of chromatin organization (GV1-3) were identified in GV oocytes according to the degree of association with the nucleolar periphery (encapsulation or "rimming"). In antral follicles > 450 microns in diameter, perinucleolar encapsulation (GV3) of oocytes before culture and meiotic maturation (metaphase II) of oocytes after culture increased (p < 0.01) with antral follicle growth in a graded fashion. While 56.3% of oocytes from large (> 1000 microns) follicles completed maturation, few (9.3%) oocytes from small (200-450 microns) follicles were competent to mature in vitro. At 0 h of culture, class IV follicles contained a greater (p < 0.01) proportion of GV3 oocytes and a smaller (p < 0.01) proportion of GV1 oocytes than classes I, II, and III follicles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8439625 TI - Development of uterus-like redifferentiation in the cervix of the ewe after exposure to estradiol-17 beta. AB - Prolonged treatment with estrogen causes the cervix of the ewe to redifferentiate to become more like uterus, and results in permanent infertility. Such permanent infertility has been observed only in ewes that have received two successive exposures to estrogen, raising the possibility that the initial exposure has a priming effect for subsequent treatment. In the study presented here, we examined whether any priming effects could be detected in the development of uterus-like histological changes in cervix of ewes given a single or two successive treatments with estradiol. Exposure to estradiol for 180 days resulted in stratified squamous hypertrophy of the cervical epithelium and also produced glandular hyperplasia, an increased proportion of lamina propria tissue in the endocervix, and fewer cervical folds. During the 30 days after treatment ceased, the epithelium returned to normal, while changes in cervical structure, as measured by reduced number of folds, became more marked. A second treatment with estradiol 180 days later produced a response similar to that after the first exposure, so it was not possible to identify any specific priming effect of the initial treatment with estrogen. However, treatment with estrogen established a process of cervical redifferentiation, and some aspects of this change appeared to be dependent on the withdrawal of estrogen. PMID- 8439626 TI - In vitro maturation of horse oocytes: characterization of chromatin configuration using fluorescence microscopy. AB - The chromatin configuration of resting horse oocytes and the time course of in vitro oocyte maturation was characterized using a fluorescent, DNA-specific label. Oocytes were classified as having either compact (CP) or expanded (EX) cumuli at the time of collection. Centrifugation of oocytes was effective in allowing visualization of the germinal vesicle. Two main chromatin configurations were found in oocytes known to have a germinal vesicle: condensed chromatin (CC), in which the chromatin formed a dense mass surrounding the nucleolus; and fluorescing nucleus (FN), in which the entire nucleus, containing diffuse or spotty chromatin, was visible. The proportion of CC to FN was higher for oocytes with EX cumuli. At time 0, 78% of CP oocytes and 73% of EX oocytes were in the germinal vesicle stage. Significantly more EX than CP oocytes were in metaphase I or II at time 0. In both CP and EX groups, maturation had not begun after 8 h of incubation. Maximal maturation occurred after 24 h for oocytes in the EX group, whereas CP oocytes continued to mature between 24 and 32 h. The percentage of EX oocytes in metaphase I did not change between 24 and 32 h, indicating a possible arrest of some EX oocytes at metaphase I. There was no difference in the percentage of oocytes at metaphase II between the CP and EX groups after 32 h of incubation. PMID- 8439627 TI - Amino acids and ammonium regulate mouse embryo development in culture. AB - The regulation of 1-cell mouse embryo development in culture by amino acids was investigated. When the 20 amino acids in Eagle's medium were present, blastocyst formation at 72 h (9%; p < 0.01), and blastocyst cell number (66; p < 0.05) and hatching (45%; p < 0.05) after 96 h of culture were significantly increased, compared to control embryos grown in the absence of amino acids (0%, 60, and 23%, respectively). The beneficial effect of Eagle's amino acids was attributed primarily to the non-essential group. In the presence of non-essential amino acids, blastocyst formation (54%; p < 0.001) and cell number after 72 h of culture (33; p < 0.05), and blastocyst cell number (69; p < 0.01) and hatching (68%; p < 0.01) after 96 h of culture were all significantly greater than for embryos cultured with all amino acids (9%, 26, 66, and 45%, respectively). In the absence of glutamine, essential amino acids significantly reduced blastocyst cell number after 96 h (53; p < 0.05). Continual culture in the presence of amino acids reduced the cleavage rate after around 72 h of in vitro culture; this decrease was not observed in the absence of amino acids. Transfer of embryos to fresh medium after 48-72 h of culture resulted in increases in the percentage of blastocysts formed and in blastocyst cell numbers. These data are consistent with the build-up of an inhibitory compound in the medium, possibly ammonium, an end product of amino acid metabolism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8439628 TI - Platelet-activating factor (PAF) in male reproductive organs of guinea pigs and rats: effect of androgen on PAF in seminal vesicles. AB - Studies were conducted on platelet-activating factor (PAF) in male reproductive organs. Total lipids were extracted from the seminal vesicles, and PAF was purified by silicic column chromatography, thin-layer chromatography, and HPLC. PAF activities in the seminal vesicles of guinea pigs and rats as measured by assay of platelet aggregation were 0.26 and 0.25 ng PAF/mumol original phospholipids. These activities were inhibited by the specific PAF antagonists CV6209 and L652,731. In guinea pigs, PAF activity decreased to 50% and 31% of the normal level 2 wk and 4 wk, respectively, after castration. The activity increased to 136% of the normal level on administration of 1 mg of testosterone propionate every day for 1 wk beginning 2 wk after castration, but decreased to 74% of the control level on administration of vehicle. Furthermore, administration of 100 IU of hCG every other day to guinea pigs resulted in increased activity, to 132% (p < 0.05) and 154% (p < 0.01) of the activity in vehicle-treated animals on Days 1 and 3, respectively. Electron microscopic studies showed changes in the rough endoplasmic reticulum of the epithelial cells of the seminal vesicles in castrated guinea pigs. (The rough endoplasmic reticulum is involved in PAF biosynthesis.) PAF activity was also demonstrated in tissues of the testis, epididymis, and vas deferens of guinea pigs and rats, and in the prostate of rats. Thus PAF may play important physiological roles in male reproductive organs. PMID- 8439629 TI - Identification and preliminary characterization of luteotropic activity in the rabbit placenta. AB - The corpus luteum of the rabbit requires estradiol (E2) and the conceptus to maintain progesterone (P4) during the second half of pregnancy. The factor produced by the fetal placenta that is responsible for maintaining P4 production has not yet been identified. Therefore, the goal of these experiments was to determine whether the rabbit placenta contained luteotropic activity and to begin preliminary characterization of this factor. A bioassay system utilizing corpora lutea explants incubated with placental extracts and other treatments was developed and validated. Neither pooled placental extracts (200 micrograms) nor E2 alone affected P4 production (p > 0.05). However, the combination of placental extracts plus E2 significantly stimulated P4 production approximately 1.5-fold (p < 0.05). Skeletal muscle (200 micrograms) + E2 also had no effect on P4 production, indicating that the effect of placental extracts was tissue-specific. Carboxymethyl-cellulose ion-exchange chromatography of placental extracts yielded four separate fractions, which were examined individually at three doses for activity in the bioassay system. The first and most acidic fraction (Fraction 1) significantly stimulated P4 production at 10 and 100 micrograms when incubated in combination with E2 (p < 0.05). Both heat and trypsin treatment abolished the ability of placental Fraction 1 to stimulate P4 production in the presence of E2. Size fractionation of Fraction 1 using dialysis membranes with 3500, 6000-8000, and 12,000-14,000 molecular weight cutoff points had no effect on bioactivity of Fraction 1. These results indicate that the rabbit placenta contains a potential luteotropin with the characteristics of an acidic, heat-sensitive protein greater than 12,000-14,000 in molecular weight. PMID- 8439630 TI - Bovine blastocyst development after in vitro maturation in a defined medium with epidermal growth factor and low concentrations of gonadotropins. AB - Higher proportions of oocytes matured in a defined medium with epidermal growth factor (EGF) and low concentrations of gonadotropins reached the blastocyst stage in vitro after in vitro fertilization than were obtained after in vitro maturation (IVM) in defined conditions alone, or with EGF and no gonadotropin. Proportions of cumulus-oocyte complexes undergoing partial and full cumulus expansion after IVM with 0, 1.0, 10.0, or 100 ng EGF/ml were 16.7%, 43.6%, 52.0%, and 63.0%, respectively; higher proportions also exhibited cumulus expansion after IVM with LH or FSH alone or in combination with EGF than after IVM in defined medium alone (p < 0.05). Varying concentrations of EGF in combination with low concentrations of either FSH or LH (0.5 micrograms/ml) for IVM increased the proportions (p < 0.05) of oocytes reaching the blastocyst stage over conditions afforded by each gonadotropin alone. For FSH+EGF at 1.0, 10.0, and 100 ng/ml, the proportions that reached the blastocyst stage were 33.7%, 39.5%, and 32.8%, respectively; for FSH alone, 13.0%. For LH+EGF at 10.0 and 100 ng/ml proportions were 33.3% and 30.8%, respectively; for LH alone, 15.3%. Combination of EGF with low concentrations of gonadotropins during IVM enabled subsequent blastocyst development in proportions comparable to those afforded by high concentrations of FSH or LH. Findings suggest a possible physiological role for EGF in regulating bovine oocyte maturation. PMID- 8439631 TI - Glycosylation of rat sperm plasma membrane during epididymal maturation. AB - Spermatozoa acquire fertilizing ability during passage through the epididymis. Modification of oligosaccharide moieties on sperm surface glycoproteins are some of the biochemical changes believed to be important in the production of functionally mature spermatozoa during passage through the epididymis. In an attempt to understand the mechanism underlying these modifications, we quantified four glycosyltransferase activities (the enzymes that catalyze the transfer of sugar residues from nucleotide sugar donor to the sugar chains on glycoproteins and glycolipids) of spermatozoa and fluid from various regions of the epididymis. Our results are as follows. (1) Only 10-20% of the total glycosyltransferase activities (sialyltransferase, fucosyltransferase, galactosyltransferase, and N acetyl glucosaminyltransferase) sedimented with the spermatozoa; the remaining 80 90% of the four enzymes were present in soluble form in the epididymal fluid. (2) When the four transferase activities were expressed per 10(6) spermatozoa, only sialyltransferase and fucosyltransferase activities showed maturation-dependent changes. The former enzyme was significantly higher on the proximal caput spermatozoa and the latter on the distal caput spermatozoa. The higher levels of the two enzymes on caput spermatozoa could be due to their binding to the endogenous sugar acceptor molecules on the sperm surface, and subsequent release following sequential sialylation and fucosylation of the molecules in the proximal and distal caput spermatozoa, respectively. (3) When spermatozoa from the proximal and distal caput, corpus, and proximal and distal cauda were incubated with fucose-labeled nucleotide sugar (GDP[14C]fucose), higher levels of radioactivity were routinely incorporated into the spermatozoa from the distal caput. (4) The [14C]fucose-labeled spermatozoa or sperm plasma membranes, when solubilized, resolved on SDS-PAGE, and visualized by autoradiography, showed that the radioactivity had been incorporated into an endogenous acceptor of 86 kDa (major component) and several minor components. Treatment of the solubilized spermatozoa with N-glycanase suggested that the [14C]fucose is mainly present on N-linked oligosaccharide units. These studies demonstrate that some of the sperm surface components are fucosylated during sperm maturation. The potential significance of the in vitro fucosylation of sperm surface components in the production of functionally mature spermatozoa is discussed. PMID- 8439632 TI - Short report: a non-metronidazole triple therapy for eradication of Helicobacter pylori infection--tetracycline, amoxicillin, bismuth. AB - Triple therapies using bismuth, metronidazole and tetracycline or amoxicillin were the first truly successful anti-H. pylori therapies. Metronidazole resistance has become an increasing problem that has severely limited the usefulness of the original triple therapy. Resistance to tetracycline or amoxicillin has not been reported and both are effective against H. pylori. We therefore tested a new triple therapy consisting of 500 mg tetracycline, 500 mg amoxicillin, and 2 tablets of bismuth subsalicylate each administered four times daily (with meals and at bedtime) for 14 days during treatment with ranitidine 300 mg daily. H. pylori eradication was defined as no evidence of H. pylori one or more months after stopping therapy. H. pylori status was evaluated by a combination of urea breath test and histology. Sixteen patients with H. pylori infection and active peptic ulcers were enrolled. The new triple therapy was successful in only 7 individuals (43%). Metronidazole appears to be critical for the effectiveness of the original triple therapy. An alternative to metronidazole will be required for a new successful triple therapy. PMID- 8439633 TI - Pantoprazole and 24-hour intragastric acidity. PMID- 8439634 TI - Review article: S-adenosyl-L-methionine--a new therapeutic agent in liver disease? AB - The established biochemical effects of exogenous S-Adenosyl-L-Methionine (SAMe) are diverse and are still being explored in liver disease. Putative therapeutic effects could be exerted via different mechanisms. The established deficiency of SAMe synthetase in cirrhosis could by bypassed by exogenous SAMe, leading to increased levels of sulphur-containing amino acids and glutathione which would protect against oxidant stress and drug-induced hepatotoxicity (for example, paracetamol). Furthermore SAMe could act by improving membrane fluidity, and thus potentially improve or restore the function of receptors, enzymes and transporters in the cell surface. Membrane fluidity is known to be affected by alterations in cell membrane lipid composition in chronic liver disease. Very few therapeutic agents are effective for the symptomatic or specific treatment of chronic liver disease. SAMe has established biochemical and biophysical effects which in pilot studies ameliorate symptoms and biochemical parameters of cholestasis. Moreover, abnormalities in liver function tests (including transaminase values) also improve. Before SAMe can be considered as an established therapy for patients with hepatic disease, long-term controlled clinical trials of SAMe are needed to assess the benefit for patients' symptoms, well being, histological changes and progression of liver disease. PMID- 8439635 TI - Early histological features of small intestinal injury induced by indomethacin. AB - The early histological features of indomethacin-induced jejunal injury in the rat are described in tissues preserved by perfusion-fixation with 10% formol-saline. After an oral dose of indomethacin (15 mg/kg, known to cause severe multifocal ulceration of the rat jejunum), groups of rats were anaesthetized with subsequent perfusion-fixation of the gastrointestinal tract at 1, 2, 3, 6 and 48 h after dosing. Using routine light microscopic techniques, we have observed a sequence of four distinct stages, in time, of small intestinal injury. The earliest histological features were shortening of the villi, epithelial stratification, basal lamina degeneration, eosinophil degranulation and infiltration of the epithelium prior to infiltration of the mucosa by neutrophils. We consider that these earliest changes, seen at 1, 2 and 3 h, represent a distinct histological entity termed Type 1 change or villous 'tufting'. Type 2 change includes all of the features of Type 1 change plus the subsequent infiltration of the mucosa by neutrophils at 2, 3 and 6 h. Type 3 change includes necrosis of the upper-third of the villi and was mainly seen at 3 and 6 h. Type 4 change describes extreme injury to more than one-third of the mucosa with severe, acute inflammation and perforation of the bowel wall by 48 h. Although a small number of neutrophils had appeared to infiltrate the mucosa as early as 2 h after dosing, they were only significantly increased at 3, 6 and 48 h. Possible pathogenic mechanisms involved in shortening of villi as a result of smooth muscle contraction and the role of mucosal eosinophils in NSAID-induced jejunal injury in the rat are discussed. PMID- 8439636 TI - Gastric and duodenal mucosal blood flow in patients receiving non-steroidal anti inflammatory drugs--influence of age, smoking, ulceration and Helicobacter pylori. AB - Using laser Doppler flowmetry, we measured gastric and duodenal mucosal blood flow in 70 patients who had taken non-steroidal anti-inflammatory drugs (NSAIDs) for longer than 4 weeks, and studied the correlation with demographic factors, ulceration, and Helicobacter pylori. Blood flow was also measured in 17 other subjects not taking any drugs. Measurements were taken from healthy-looking mucosa in the gastric antrum and the first part of the duodenum. Both gastric and duodenal blood flow values were significantly lower in patients taking NSAID than in those who did not. In the NSAID group, the median duodenal mucosal blood flow was 150 perfusion units in smokers (n = 29) compared with 175 in non-smokers (P = 0.024), 123 units in patients with duodenal ulcers (n = 12) compared with 160 in those without duodenal ulcers (P = 0.020), 135 units in patients with H. pylori (n = 30) compared with 168 in patients without H. pylori (P = 0.033), and 118 in smokers infected with H. pylori compared with 175 units in non-smokers not infected with H. pylori (F = 13.4, P = 0.0005). There was no correlation with age. Gastric blood flow was not significantly influenced by any of the above variables. These results suggest that chronic NSAID intake is associated with reduced blood flow in both the stomach and duodenum. However, amongst NSAID patients, duodenal, but not gastric, mucosal blood flow is reduced in smokers, and in those with duodenal ulcers and H. pylori.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8439637 TI - Early evening nizatidine intake with a meal optimizes the antisecretory effect. AB - The importance of the temporal relationship between meal and nizatidine intake was studied in a six-armed, double-blind, placebo-controlled trial. Eleven healthy volunteers received early (18.00 hours) or late (21.00 hours) supper, with either placebo, early (18.00 hours) nizatidine, or late (21.00 hours) 300 mg nizatidine. Ambulatory 21-hour gastric pH-metry was performed and plasma nizatidine concentrations were determined by high pressure liquid chromatography. Early-nizatidine/early-supper (median pH 2.50), but not late-nizatidine/late supper (median pH 2.30), produced significantly higher median 21-hour pH values than did early-nizatidine/late-supper (median pH 1.90). Concomitant food delayed the absorption of nizatidine but did not change the drug's bioavailability. Oral nizatidine should be taken with food, preferably early in the evening, to optimize its anti-secretory effect. PMID- 8439638 TI - Dose-dependent stimulation of gallbladder contraction by intravenous erythromycin in man. AB - We have previously shown that a single oral dose of 500 mg erythromycin causes gallbladder contraction. The effect of intravenous erythromycin on antroduodenal motility is dose-dependent; < 3 mg/kg body weight stimulates propagated contractions in a fashion similar to motilin while doses > 7 mg/kg cause giant non-propagated antral contractions not seen with motilin. Using ultrasound, we have examined the effect of differing doses of intravenous erythromycin on gallbladder motility in man. Erythromycin (1 mg/kg) caused fasting gallbladder contraction to 52% of basal gallbladder volume (P < 0.001), and increased gallbladder emptying following a liquid meal (maximal percentage emptied 75 +/- 6.8% vs. 58 +/- 9.0% following saline, P < 0.05). Erythromycin (7 mg/kg) however, had no effect on gallbladder fasting or post-prandial motor activity. We conclude that the effect of erythromycin on gallbladder motility is dose-dependent, with higher doses having no effect. It is possible that at higher doses erythromycin stimulates other receptors in addition to the motilin receptor, and that the combined effect is different to the stimulation of the motilin receptor alone. PMID- 8439639 TI - Omeprazole is superior to ranitidine plus metoclopramide in the short-term treatment of erosive oesophagitis. AB - Histamine H2-receptor antagonists are moderately effective in symptomatic treatment and healing of erosive oesophagitis, but they are not as effective as the proton pump inhibitor omeprazole. In some studies prokinetic agents seem to increase the effectiveness of H2-antagonists, but no study comparing the efficacy of omeprazole to H2-antagonists plus prokinetic agents has been performed. The purpose of this study was to compare the efficacy and tolerability of 20 mg omeprazole daily with 150 mg ranitidine b.d.s. plus the prokinetic agent 10 mg metoclopramide q.d.s. in patients with erosive oesophagitis. After both 4 and 8 weeks of treatment, omeprazole healed the mucosa in significantly more patients than did ranitidine plus metoclopramide. Omeprazole also provided significantly greater relief from daytime heartburn, nighttime heartburn, and acid regurgitation, and was associated with decreased concomitant antacid use. Although the overall incidence of adverse events was similar in the two treatment groups, a significantly higher number of treatment-related adverse events and more treatment-related withdrawals from the study occurred in the ranitidine plus metoclopramide treatment group. Omeprazole is more effective and better tolerated than the combination of standard dose ranitidine plus metoclopramide for patients with erosive oesophagitis. PMID- 8439640 TI - The effect of trospium chloride on oesophageal motility. AB - Trospium chloride is a muscarinergic antagonist acting on oesophageal smooth muscle and on ganglionic and/or myenteric neurons. The effect of this drug on oesophageal motility was tested in 16 healthy male subjects in a double-blind randomized cross-over examination of trospium chloride or placebo following phentolamine or placebo application. Each subject underwent two separate investigations at least one week apart. Trospium chloride was effective in the oesophagus to reduce contractile activity (amplitude and duration of peristalsis) in all parts of the oesophageal body, and this effect was not blocked by phentolamine. Its potent action and its minor side-effects appear to be promising for clinical use in patients with motility disorders such as the hypercontractile oesophagus. PMID- 8439641 TI - Cimetidine improves GERD symptoms in patients selected by a validated GERD questionnaire. AB - A questionnaire was constructed and validated to improve the accuracy of symptom assessment in diagnosing gastro-oesophageal reflux disease (GERD). The GERD questionnaire consisted of four questions describing an upward moving, uncomfortable feeling in the chest frequently accompanied by retrosternal burning that is improved with antacids. It was found that if a patient answered yes to all four questions the likelihood was 85% that erosive oesophagitis would be detected on endoscopy or that pathological gastro-oesophageal reflux on 24-hour pH-monitoring would be documented, or both. The GERD questionnaire was used to identify 269 patients with probable GERD who after one week on placebo entered a 2-week double-blind placebo-controlled study which was completed by 251 patients. Cimetidine (400 mg) b.d. was given to 124 patients and placebo to 127 patients. On diary cards the patients noted the number, the mean duration and the mean severity of GERD symptoms episodes. Cimetidine was significantly superior to placebo in increasing the percentage of symptom-free days, and in reducing the median number of daily symptom episodes. This trial demonstrates that 400 mg cimetidine b.d. is effective in improving GERD symptoms in patients identified by a descriptive, validated GERD questionnaire. PMID- 8439642 TI - Calcium polycarbophil compared with placebo in irritable bowel syndrome. AB - Calcium polycarbophil was compared with placebo in 23 patients with irritable bowel syndrome in a six-month, randomized double-blind crossover study. Patients received polycarbophil tablets at a dosage of 6 g/day (twelve 0.5-g tablets) or matching placebo tablets. At study end, among patients expressing a preference, 15 of 21 (71%) chose polycarbophil over placebo for relief of the symptoms of irritable bowel syndrome. Statistically significant differences favouring polycarbophil were found among the following patient subgroups: 15 (79%) of 19 with constipation: all six with alternating diarrhoea and constipation; 13 (87%) of 15 with bloating: and 11 (92%) of 12 with two or more symptoms. Polycarbophil was rated better than placebo in monthly global responses to therapy. Patient diary entries showed statistically significant improvement for ease of passage with polycarbophil. Polycarbophil was rated better than placebo for relief of nausea, pain, and bloating. The data suggest that calcium polycarbophil can benefit irritable bowel syndrome patients with constipation or alternating diarrhoea and constipation and may be particularly useful in patients with bloating as a major complaint. PMID- 8439643 TI - Rolling review: autoimmune liver disease. PMID- 8439644 TI - Glomerular preload and afterload reduction as a tool to lower urinary protein leakage: will such treatments also help to improve renal function outcome? AB - It has been well documented that different therapeutic strategies, including angiotensin-converting enzyme (ACE) inhibitors, nonsteroidal anti-inflammatory drugs, and dietary protein restriction, lower urinary protein excretion in patients with diabetic and non-diabetic nephropathy. Experimental evidence suggests that this antiproteinuric effect is, at least in part, related to a reduction in the glomerular capillary hydraulic pressure. ACE inhibitors appear to achieve this reduction in glomerular capillary pressure, mainly through a fall in postglomerular arteriolar resistance, whereas dietary protein restriction and non-steroidal antiinflammatory drugs appear to invoke the response predominantly through an increase in preglomerular resistance. This leads to the suggestion that both "glomerular preload reduction" (afferent vasoconstriction) and "glomerular afterload reduction" (efferent vasodilation) will result in an anti proteinuric response. Interestingly, these same therapeutic regimens, particularly the ACE inhibitors and low-protein diets, have been proven to prevent progressive glomerulosclerosis in animal models. This concept of influencing glomerular hemodynamics both at the afferent and efferent arteriolar level may open new perspectives in the treatment of patients with renal protein loss and renal failure. At present, however, it is too early to conclude whether the fall in proteinuria induced by these treatments will also contribute to a better renal survival of these patients. PMID- 8439645 TI - Species-specific properties of the glomerular mesangium. AB - Mesangial cells play a central role in the physiology and pathophysiology of the glomerulus. To date, most of the in vitro studies have been performed in cultured rat mesangial cells, with only 10% of them performed in human mesangial cells. In this article, the major differences between results obtained with these two types of cultured cells will be reviewed. In rats and in humans, most of the mesangial cells appear to be of smooth muscle origin. In the rat, some of the cultured cells also express a phenotype suggesting a monocyte/macrophage origin. Phagocytosis and synthesis of cytokines or proinflammatory proteins that have been described in cultured rat cells seem mostly linked to this monocyte/macrophage subtype of resident mesangial cells. In humans, macrophages are only detected in pathologic conditions, suggesting that they are not resident but rather infiltrating cells. Mesangial receptors, most notably angiotensin II receptors, are clearly present on mesangial cell membranes and are linked to prostaglandin E2 synthesis and to cell contraction. In humans, spontaneous prostanoid synthesis is low and is increased by the induction of cyclooxygenase by sodium butyrate in the medium. Even so, the amount of prostaglandin E2 synthesized by human mesangial cells is quantitatively low comparatively with that in rats. In rats, accordingly, mesangial cells play a role in the regulation of single-nephron GFR. In humans, angiotensin II also exerts a control on GFR but it is more difficult to demonstrate its contractile effect on human than on rat mesangial cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8439646 TI - Secondary syphilis and the nephrotic syndrome. AB - A case of nephrotic syndrome in a 21-yr-old black man with secondary syphilis and diabetes mellitus is described. A renal biopsy was performed, which showed membranous glomerulopathy stage I associated with mesangial hyperplasia and mesangial deposits. The clinical course and the histologic findings, compatible with syphilitic nephropathy, are offered to remind internists (nephrologists) that sexually transmitted diseases, like syphilis or hepatitis B, in addition to human immunodeficiency virus, can have important renal manifestations. PMID- 8439647 TI - Clinical clues to understanding the early course of diabetic nephropathy. PMID- 8439648 TI - Slope of serial glomerular filtration rate and the progression of diabetic glomerular disease. AB - Glomerular function was evaluated longitudinally over a 24- to 48-month period in 18 patients with diabetic glomerular disease (DGD) manifested by proteinuria. GFR was determined by iothalamate clearance at 4-month intervals. The patients were divided into two groups: Group 1 (N = 9) had subnephrotic proteinuria and an initially normal GFR of 91 +/- 8 mL/min. Group 2 (N = 9) had nephrotic-range proteinuria, and initial GFR was reduced to 53 +/- 5 mL/min. Serial GFR fluctuated over time in Group 1, but no trend towards hypofiltration was evident. In contrast, GFR declined linearly in Group 2 at 1.1 +/- 0.3 mL/min per month. The transglomerular sieving of uncharged dextrans of graded size was analyzed and initially revealed a uniform reduction in glomerular pore density and an enhancement of shuntlike pores. Pore density was initially reduced by 80% and declined further after 24 months in nephrotic Group 2; corresponding pore density in subnephrotic Group 1 was reduced by half but remained constant. Renal biopsy of four members of Group 1 revealed a 22% prevalence of global glomerulosclerosis. Remaining open glomeruli exhibited hypertrophy, excessive extracellular matrix, and deformation of epithelial podocytes. The latter abnormality appeared to be the predominant determinant of lowered ultrafiltration capacity. It was inferred that trials of therapy to attenuate the progression of DGD should be initiated at a functional level similar to that in subnephrotic Group 1. Because GFR is unlikely to decline over a 2- to 4-yr period, it is suggested that such trials be extended for longer periods. Alternatively, morphometric analysis of serial renal biopsies may shorten the time needed to demonstrate effective renoprotection in DGD. PMID- 8439649 TI - Renal functional reserve in healthy elderly subjects. AB - The increase in GFR after an amino acid (AA) load, the so-called renal functional reserve, is impaired in the aged rat. Whether the renal functional reserve predicts the progression of renal disease in humans is controversial, but it is possible that age-related alterations of renal hemodynamics are relevant for the evolution of renal disease in the elderly. We compared renal hemodynamics before and after an AA infusion in 15 healthy normotensive subjects of young age (seven women, eight men; median age, 26 yr; range, 23 to 32) and in 10 subjects of old age (six women, four men; median age, 70 yr; range, 61 to 82) on normal dietary protein intake. Baseline GFR and effective RPF were measured after 12 h of fasting by the inulin (Cin) and para-aminohippurate (Cpah) steady-state infusion techniques. The renal functional reserve was examined after an overnight AA infusion (7% solution; 83 mL/h). Median basal Cin and Cpah were significantly lower (P < 0.01) in the elderly (102 and 339 mL/min per 1.73 m2) than in the young subjects (122 and 647 mL/min per 1.73 m2), but virtually all GFR values of the elderly were still within the normal range. Median Cin upon infusion of AA was 118 mL/min per 1.73 m2 (range, 98 to 137) in the elderly and 146 (range, 120 to 171) in the young, respectively. Corresponding values of Cpah were 349 mL/min per 1.73 m2 in the elderly versus 689 mL/min per 1.73 m2 in the young. Cin increased significantly (P < 0.01) after the AA load in both young and elderly subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8439650 TI - Extracellular matrix component mRNA expression in glomeruli in experimental focal glomerulosclerosis. AB - This study was designed to assess how the expression of genes for components of the extracellular matrix is altered in a model of focal glomerular sclerosis. In this model, a unilateral nephrectomy combined with injections of puromycin aminonucleoside induces a much higher incidence of focal glomerular sclerosis. Rats received puromycin aminonucleoside on days 0, 27, 34, and 41 and underwent unilateral nephrectomy on day 22. Control rats received physiologic saline injections with and without unilateral nephrectomy. Rats from each group were killed on days 48, 60, and 80. The steady-state levels of glomerular mRNA encoding type IV collagen, the B1 and B2 chains of laminin, heparan sulfate proteoglycan, and type I and type III collagens were compared in both the puromycin aminonucleoside-treated and the control glomeruli. The mRNA levels encoding type IV collagen and laminin B1 and B2 were increased three-, two-, and twofold, respectively, on day 48 of focal glomerular sclerosis. These transcripts were further increased eight-, seven-, and eightfold, respectively, on day 80 compared with the control glomeruli (P < 0.01). In contrast, heparan sulfate proteoglycan mRNA levels were not increased on day 48 when the animals had marked proteinuria. However, the heparan sulfate proteoglycan mRNA levels did become elevated by day 60 and remained elevated thereafter. The expression of type I and type III collagen mRNA was increased 12- and 7-fold, respectively (P < 0.01), on day 80 in focal glomerular sclerosis rats compared with the controls. An immunofluorescence study revealed the accumulation of immunoglobulin M, C3, type IV collagen, laminin, heparan sulfate proteoglycan, and type I and type III collagens in the sclerotic area. These data indicate that changes in the mRNA levels for components of the basement membrane and interstitial collagen are associated with the development of glomerular sclerosis. PMID- 8439651 TI - Glomerular epithelial cells produce endothelin-1. AB - Endothelin-1, a vasoactive peptide originally isolated from vascular endothelial cell culture supernatants, has constricting or mitogenic effects on smooth muscle and glomerular mesangial cells. Whether or not cultured rat glomerular epithelial cells synthesize endothelin-1 was assessed. Under basal culture conditions, the synthesis and release of endothelin-1 peptide by glomerular epithelial cells was time dependent, reaching 0.231 +/- 0.017 pg/1,000 cells at 24 h. For comparison, unstimulated bovine pulmonary artery endothelial cells and rat mesangial cells produced 0.982 +/- 0.237 and 0.004 +/- 0.002 pg of endothelin-1 peptide/1,000 cells per 24 h, respectively. In addition to endothelin-1 peptide, unstimulated glomerular epithelial cells expressed preproendothelin-1 mRNA. Transforming growth factor-beta, complement C5b-9, thrombin, and phorbol myristate acetate significantly enhanced endothelin-1 peptide synthesis in glomerular epithelial cells (45, 15, 55, and 25% above basal levels at 24 h, respectively), whereas epidermal growth factor had no effect. Thrombin and phorbol myristate acetate appeared to stimulate endothelin-1 peptide by activating protein kinase C, because the protein kinase inhibitor 1-(5-isoquinolinyl-sulfonyl)-3-methyl piperazine abolished the thrombin- and phorbol myristate acetate-induced rise in endothelin-1 but had no effect on basal production. The stimulatory effect of thrombin was also markedly diminished in glomerular epithelial cells that had been depleted of protein kinase C by prolonged preincubation with a high dose of phorbol myristate acetate. Thus, glomerular epithelial cells may be an important source of endothelin-1, which might influence glomerular vasoconstriction or proliferation of target cells, particularly in the presence of proinflammatory molecules in the glomerulus. PMID- 8439652 TI - Chronic in-center hemodialysis patients' attitudes, knowledge, and behavior towards advance directives. AB - Forty-three chronic in-center hemodialysis patients were asked about their knowledge, attitudes, and behavior towards advance directives. The survey collected patient demographic data and assessed attitudes, knowledge, and behavior towards advance directives by agreement or disagreement with statements. Sixty-six percent of patients did not know what a health care proxy was, and 42% did not know the legal status of a living will. However, 90% of older patients (> or = 60 yr of age) understood living wills. Although 77% of the patients had discussed their wishes about life-sustaining care with someone close to them, only 17% had had such discussions with their doctor. Twenty-one percent had completed an advance directive. Fifty percent of patients agreed with the statement that a potential problem with advance directives was that patients could change their minds about heroic treatments; 51% agreed that advance directives might interfere with a doctor's judgment. Only 26% agreed that a dialysis unit's promotion of the use of advance directives might lead to undertreatment. Patient age, race, marital status, and time on dialysis did not affect responses. A prior failed transplant and the educational level completed by the patient influenced some specific responses. Despite some concern, 79% of patients agreed that a dialysis unit policy asking patients whether they had completed an advance directive was a good idea. PMID- 8439653 TI - Improvement of plasma lipoprotein profiles during high-flux dialysis. AB - Patients undergoing maintenance hemodialysis therapy have increased mortality due to cardiovascular disease. One possible etiologic factor for this increased mortality is the lipid abnormalities associated with chronic renal failure. These include elevated triglyceride (TG) and decreased high-density lipoprotein (HDL) concentrations. Lipoprotein profiles of patients undergoing chronic hemodialysis with either saponified cellulose ester (CE) (N = 9) or polysulfone (PS) high-flux dialysis membranes (N = 10) were compared. Patients in each group received similar amounts of heparin during the dialysis. CE-dialyzed patients showed no alteration in serum TG, HDL, low-density lipoprotein, or total cholesterol when predialysis and postdialysis values were compared. PS patients, on the other hand, had a significant decrease in TG concentrations (P < 0.01) as well as a significant rise in HDL (P < 0.01). These changes might signify activation of lipoprotein lipase (LPL) during dialysis. LPL activity in PS sera was significantly greater than LPL in CE sera. Moreover, sera from PS patients inhibited LPL much less than did sera from CE patients. These findings suggest that a circulating substance not dialyzable with cellulosic membranes inhibits LPL in uremic subjects and is removed during dialysis with a PS membrane. Alternatively, the greater biocompatibility of PS may produce less LPL inhibitory cytokines during dialysis. The improvement of lipoprotein profiles in patients receiving dialysis with PS membranes may, in the long term, lead to less morbidity and mortality from atherosclerotic disease. PMID- 8439654 TI - Acid-base regulation of hepatic glutamine metabolism and ureagenesis: study with 15N. AB - The metabolism of (5-15N)glutamine and (2-15N) glutamine has been studied by isolated hepatocytes obtained from either control, chronically acidotic, or alkalotic rats. The main goal was to elucidate the mechanism(s) by which altered acid-base state affects hepatic ureagenesis from glutamine. Isolated hepatocytes were incubated in Krebs buffer (pH 7.4) supplemented with 0.1 mM ornithine plus either 1 mM (5-15N)glutamine or (2-15N)glutamine. To elucidate the role of glutamine cycling in net ammonia metabolism, a separate series of experiments were performed with 1 mM unlabeled glutamine plus 1 mM (15N)H4Cl. Net glutamine utilization was significantly lower in hepatocytes obtained from chronically acidotic rats compared with control or alkalotic rats. The sum of the rates of 15NH3 and (15N)urea production from (5-15N)glutamine was decreased in acidosis compared with alkalosis. After incubations of 50 min, approximately 75, 65, or 90% of the N in carbamoyl-phosphate was derived from the 5-N of glutamine in control, acidosis, or alkalosis respectively. In experiments with (2 15N)glutamine, the production of singly and doubly labeled (15N)urea as well as (15N)aspartate and (15N)H3 was significantly smaller in acidosis compared with alkalosis. Furthermore, a correlation was observed between production rates of (15N)aspartate and (15N)urea, suggesting that alterations in urea production may depend on aspartate formed from glutamine. However, the production of (15N)alanine was higher in acidosis compared with alkalosis with apparent correlation between the production of (15N)alanine and 2-oxoglutaramate, a product of the glutamine aminotransferase pathway. In addition, the rate of glutamine recycling was significantly higher in acidosis compared with control or alkalosis, indicating that both flux through glutamine aminotransferase and flux through glutamine synthetase were elevated in acidosis compared with alkalosis. These data suggest that decreased formation of aspartate from glutamine may limit ureagenesis in chronic metabolic acidosis. The formation of aspartate may depend on the availability of oxaloacetate rather than diminished flux through transaminase reaction. The enhancement of alanine production and glutamine synthesis may provide an alternate route of N disposal in cases of diminished urea formation. PMID- 8439655 TI - Glucocorticoid-induced changes in the quantity and secretory capacity of individual rat somatotropes. AB - Chronic glucocorticoid treatment is complicated by growth failure. The study presented here was designed to investigate the effect of cortisone on growth hormone (GH) secretion by individual pituitary cells in young male rats. Beginning at 37 days of age, animals were injected sc with cortisone acetate (CORT; 5.0 mg/rat per day) or the same volume of saline (SAL) for 8 days. At 45 days of age, the body weights of the CORT animals (134.5 +/- 5.5 g) were significantly less (P < 0.0005) than those of SAL controls (179.3 +/- 4.2 g). The secretory capacity of dispersed pituitary cells was assessed by the reverse hemolytic plaque assay. Cells were exposed to six concentrations of GH-releasing hormone (GHRH) ranging from 0.01 to 3.0 nM. CORT treatment significantly decreased the absolute number of somatotropes per pituitary gland (CORT, 1.23 +/- 0.03 x 10(6); SAL, 1.57 +/- 0.09 x 10(6); P = 0.025). Conversely, the mean plaque areas were significantly greater for CORT animals at all concentrations of GHRH tested, indicating that the amount of GH secreted by individual somatotropes was significantly increased by CORT. It was concluded that the paradoxical increase in the in vitro GHRH responsiveness, which is commonly observed after glucocorticoid treatment, was due to an increase in the capacity of fewer individual somatotropes to secrete GH. PMID- 8439656 TI - Verrucous carcinoma of the oesophagus and achalasia. AB - A 67 year old male caucasian clerical worker with a background of long-standing gastro-oesophageal reflux-like dyspepsia and bronchiectasis presented to a tertiary hospital gastroenterology unit with a recent onset of dysphagia. An initial diagnosis of achalasia was made and within 1 year an established verrucous carcinoma of the upper oesophagus had developed. The tumour was inoperable due to tracheal invasion and therefore palliative treatment was given. The patient developed a tracheo-oesophageal fistula and died of pneumonia. Thus, verrucous squamous cell carcinoma of the oesophagus can occur with achalasia. PMID- 8439657 TI - Bacterial invasion into the colonic mucosa in ulcerative colitis. AB - This study investigated interactions between mucosal lesions and bacterial invasion in ulcerative colitis using the acridine-orange staining method. In all 16 cases of ulcerative colitis, the mucosa was found to be invaded by small rods and cocci. In five of 10 controls, bacteria were seen only adhering to the mucosa and no bacteria were detected in the five remaining cases. It is suggested that the presence of bacteria in the colonic mucosa may be a factor responsible for the persistence or aggravation of ulcerative colitis. PMID- 8439658 TI - Differential regulation of ferritin H and L subunit mRNA during inflammation and long-term iron overload. AB - Iron overload, such as occurs in the genetic disease haemochromatosis, leads to synthesis of ferritin containing an increased proportion of L subunits. Inflammation also leads to clinically important increases in ferritin synthesis but the predominant subunit involved is unclear. Elevation of serum ferritin concentration during the acute phase response confounds its use as an indicator of body iron stores and identification of the major subunit involved may allow distinction of the ferritin associated with inflammation from the synthesized during iron overload. The present study examined H and L ferritin subunit mRNA levels in rats with: (i) longstanding iron overload, both parenteral and oral, in which changes should be maximal and stable; and (ii) inflammation of 24 and 48 h duration. A two-fold increase in L mRNA level was found in both groups of iron loaded animals while H mRNA level was unchanged. This finding would account for the observed preponderance of L subunits in ferritin during iron overload. During the course of inflammation there was a progressive decrease in L mRNA level in the liver but not the spleen. H mRNA relative to total RNA level was unchanged in both liver and spleen. It is concluded that the differential regulation of the two ferritin subunits in response to different stimuli and in different tissues occurs at the level of alteration in mRNA concentration. PMID- 8439659 TI - Bacterial biofilm, brown pigment stone and blockage of biliary stents. AB - Bacterial pathogens gain access into the biliary system by descending via the portal venous circulation or ascending through the sphincter of Oddi in duodenal biliary reflux. Bacteria thrive as glycocalyx-enclosed microcolonies, coalescing to form an adherent biofilm. The establishment of biofilm is a key event in the formation of biliary sludge and pigment gallstones, and the blockage of biliary stents. The biofilm mode of growth is very effective because it provides bacteria with a measure of protection from antibacterial agents and phagocytic leucocytes. Calcification of the matrix confers further protection for the micro-organisms living inside the biofilm. To date, attempts to prevent blockage of biliary stent have employed physical methods by using large self-expandable stents and stents without side hole. Incorporation of antibiotics within stents has not been successful presumably because bacteria once living in their biofilm are quite resistant to antimicrobial agents. Even the most toxic bile salts have no effect on the biofilm bacteria. Yet, hydrophobic bile salts reduce bacterial adhesion on biomaterial, suggesting that incorporation of such bile salts might prevent the formation of bacterial biofilm. PMID- 8439660 TI - Emergency endoscopic nasobiliary drainage for acute calculous suppurative cholangitis and its potential use in chemical dissolution. AB - Acute suppurative cholangitis is one of the common causes of acute abdomen in Taiwan. Emergency decompression is a life-saving procedure if patients fail to respond to antibiotic treatment. From July 1988 to June 1991, 224 patients were encountered with concomitant bile duct stones and cholangitis; 40 were brought to the emergency service with shock or mental confusion or responded poorly to antibiotic treatment. The patients consisted of 20 males and 20 females aged 21 81 years (mean age 64 years); 55% had intrahepatic duct stones, 50% had positive blood culture, 38% had undergone previous biliary surgery, 25% had concomitant medical illnesses and 20% presented with mental confusion. Emergent endoscopic nasobiliary drainage (ENBD) was performed within 48 h of each patient's arrival in the emergency room. In 3 days all the patients exhibited significant improvement as defined by body temperature, vital signs, white blood cell count, serum bilirubin and alkaline phosphates levels. When their condition had stabilized, 21 patients underwent elective surgery. Six patients received ethylenediaminetetraacetic acid infusion through an ENBD tube. Two of the patients' stones dissolved completely. Six patients received papillotomy with stone removal. The remaining patients refused further treatment. There was no hospital mortality. It is therefore concluded that ENBD offers an effective treatment for acute calculus suppurative cholangitis and it is a potential route of administration for the chemical dissolution of bile duct stones. PMID- 8439661 TI - Quantitative immunohistochemical analysis of lymphocyte subsets in alcoholic liver disease. AB - To investigate the role of lymphocytes frequently observed in the parenchyma of alcoholic liver disease (ALD), lymphocytes infiltrating into the liver were stained immunohistochemically with monoclonal antibodies (MoAb) and were quantitatively assessed by a morphometric analysis in 17 patients with ALD and, for comparison in five patients with chronic active hepatitis B (B-CAH). In patients with alcoholic hepatitis, the number of CD8+ lymphocytes in the hepatic lobule was similar to that in patients with B-CAH but was significantly greater than that in alcoholics with hepatic fibrosis (HF). The CD4/CD8 ratio in the hepatic lobule was low in both alcoholic hepatitis and B-CAH compared with that of alcoholic patients with HF. When Mallory bodies (MB) and lymphocytes were simultaneously stained with a specific antibody against MB and MoAb, respectively, only CD3+ and CD8+ lymphocytes were found to have a close contact with MB. These results suggest that in alcoholic hepatitis, hepatocyte necrosis may be partly mediated by immunological mechanisms involving cytotoxic T cells infiltrating into the hepatic lobule. PMID- 8439662 TI - Therapeutic upper gastrointestinal endoscopy in children: an audit of 443 procedures and literature review. AB - The safety, effectiveness and capabilities of therapeutic upper fibreoptic endoscopy in children undergoing therapeutic endoscopic procedures (n = 443) was studied. Therapy for gastrointestinal bleeding formed the major group (injection sclerotherapy for varices, n = 197 procedures; thermocoagulation for haemorrhagic gastritis, n = 1; and photocoagulation for Dieulafoy's disease, n = 1). Sclerotherapy was 97% effective in controlling acute bleeding and 84% effective in obliterating varices with no serious complications or deaths. Oesophageal dilatations for surgical, caustic, congenital and peptic strictures and achalasia (n = 193) were performed with no oesophageal perforations or deaths. Foreign bodies were retrieved (n = 34) with no failures or complications. Percutaneous endoscopic gastrostomy was performed (n = 11) with one failure, proceeding to an unsuccessful surgical gastrostomy. Miscellaneous procedures included endoscopic transpyloric tube placement (n = 5) and endoscopic diathermy of pyloric web (n = 1). Therapeutic fibreoptic endoscopy is therefore concluded to be safe and effective in children, replacing rigid oesophagoscopy and some traditional surgical approaches. PMID- 8439663 TI - Protective effect of a cephalosporin, Shiomarin, plus a new potent protease inhibitor, E3123, on rat taurocholate-induced pancreatitis. AB - The role of infectious factors in the pathogenesis of acute pancreatitis and the protective effect of combined therapy with a new potent synthetic protease inhibitor, E3123, and a new potent synthetic cephalosporin, Shiomarin were examined in rat acute pancreatitis. Sodium taurocholate injection into the pancreatico-biliary duct of rats caused severe pancreatitis with a high mortality rate, characterized by hyperamylasaemia, high amylase activity in ascitic fluid, hyperendotoxaemia and a high serum level of fibrin degradation products (FDP) and redistribution of cathepsin B from the lysosomal fraction to the zymogen fraction. Sodium taurocholate injection into the pancreatico-biliary duct also caused the bacterial growth in the pancreas. In rats with E3123 infusion almost all parameters were improved, including mortality rate, serum and ascitic fluid amylase levels, plasma endotoxin and serum FDP levels, and distribution of lysosomal enzyme. But combination therapy with E3123 and Shiomarin was significantly more protective than E3123 therapy alone. These results indicate that infection plays an important role in the development of severe pancreatitis and that combination therapy with a new synthetic protease inhibitor and a new potent antibiotic may be useful in the treatment of severe pancreatitis. PMID- 8439664 TI - Gastrointestinal involvement in homocystinuria. AB - Homocystinuria is frequently associated with severe multisystem involvement such as dislocated lenses, skeletal deformities, mental retardation and premature vascular occlusions. Surprisingly, gastro-intestinal involvement has not been described in this disorder. We present a 17 year old boy with homocystinuria due to cystathionine beta-synthase deficiency, who developed severe gastrointestinal involvement, manifested by chronic diarrhoea and acute pancreatitis. The diarrhoea was successfully treated with betaine. Possible pathophysiological mechanisms and suggested treatment are described. PMID- 8439665 TI - Significant changes in intestinal lymphatic system and immune response elicited by Peyer's patch excision in adult rats. AB - The effect of deprivation of Peyer's patches (PP) on transport of lymphocytes through intestinal lymph and intestinal mucosal immune responses was investigated in rats. All visible PP in the rat small intestine were excised in order to examine the roles of PP in the intestinal lymphatic system and mucosal immune responses of the intestine. Two weeks after the experimental excision of PP, lymphocyte transport in intestinal lymph was significantly decreased in PP excised rats without significant changes in lymphocyte subsets as compared with sham operated control rats. Lymphocyte subsets as determined morphometrically in the intestinal mucosa showed no significant alteration in PP-excised rats. There was a significant decrease in the number of immunoglobulin A (IgA) containing cells in the intestinal mucosa of PP-excised rats, while IgM and IgG containing cells showed no statistically significant changes in number. Conversely, the macrophages in the intestinal mucosa increased in number, suggesting the enhanced accessory functions of these macrophages. Antigen-specific immune response was further studied in PP-excised rats using intraduodenal priming and challenge with cholera toxin (CT). Both the determinations of cells producing antigen-specific antibody in the intestinal mucosa using anti-CT antibody and those of cells secreting anti-CT Ig in the intestinal lymph by enzyme-linked immunospot (ELISPOT) assay showed a significant reduction of CT-specific antibody production in PP-excised rats compared with controls. Peyer's patches appear to have an important role in lymphocyte transportation through intestinal lymph and also in mucosal immune responses. PMID- 8439666 TI - Spontaneous occurrence of autoimmune cholangitis in senescent mice. AB - The biliary lesions that developed spontaneously in senescent female C57BL/6NCrj mice were investigated. Degeneration of the bile duct epithelium was observed in 12 of 13 mice (92%), destruction of bile duct epithelial cells was seen in six of 13 mice (46%) and chronic non-suppurative destructive cholangitis was found in three of 13 mice (23%). The biliary lesions were characterized by prominent round cell infiltrates in the portal areas. Extra-hepatic lesions such as sialoadenitis were observed in six mice (46%) and pancreatis in seven (53%). IgM class antipyruvate dehydrogenase antibody was positive in one of three C57BL/6NCrj mice not given anti-Lyt 2 antibody and in three of six C57BL/6NCrj mice injected with anti-Lyt 2 antibody. These lesions were not observed in male C57BL/6NCrj mice, young female C57BL/6NCrj mice, or ICR mice. However, by transferring the splenic cells of senescent female C57BL/6NCrj mice to 6 week old females, the biliary lesions could be transferred at the rate of 6/9. The lymphocytes infiltrating in the bile ducts were CD8 positive lymphocytes. Moreover, in the ultrastructural immunocytochemical analysis of lymphocytes infiltrating bile duct epithelia, CD8 positive lymphocytes often formed broad contacts with the epithelial cells. The biliary lesions developing spontaneously in these mice are similar to those found in human primary biliary cirrhosis. PMID- 8439667 TI - The liver in systemic lupus erythematosus. PMID- 8439668 TI - Pathogenesis and assessment of malnutrition in liver disease. PMID- 8439669 TI - pSym nod gene influence on elicitation of peroxidase activity from white clover and pea roots by rhizobia and their cell-free supernatants. AB - The activities of salt-elutable peroxidases from roots of white clover and pea were examined during the early interaction of these legume hosts with strains of Rhizobium leguminosarum in homologous and heterologous combination. Peroxidase specific activity from clover root hairs began to increase 6 hr after inoculation with R. l. bv. viciae RL300 and was localized over the entire area of their deformations. In contrast, the onset of elicitation of peroxidase activity from root hairs was delayed after inoculation with R. l. bv. trifolii ANU843 and was localized only at the site of infection thread initiation. Three wild-type strains (R. l. bv. trifolii ANU843, R. l. bv. viciae RL300 and 1003) and one hybrid transconjugant strain of R. leguminosarum containing pSym from R. l. bv. viciae 248 (RBL5715) elicited increased specific activity of peroxidases eluted from pea and clover roots in heterologous combination. A comparison of peroxidase activity eluted from pea roots inoculated with ANU843 or its pSym-cured derivative indicated that pSym is required for elicitation of peroxidase on this heterologous host. The level of peroxidase activity elicited by nodE mutants (which have extended host range) is decreased on their new host. An extracellular fraction of RL300 contained flavonoid-dependent, heat-stable, and ethanol-soluble elicitor(s) of peroxidase activity. Treatment of clover seedlings with this cell free fraction decreased the number of root hairs infected by ANU843. We propose that elicitation of root hair peroxidase may contribute to the infection process in this Rhizobium-legume symbiosis by altering root hair wall structure at sites of incipient penetration. PMID- 8439670 TI - Genetic analysis of the Rhizobium meliloti exoYFQ operon: ExoY is homologous to sugar transferases and ExoQ represents a transmembrane protein. AB - The nucleotide sequence of a 4.8-kb ClaI-EcoRI DNA fragment of megaplasmid 2 of Rhizobium meliloti Rm2011 involved in succinoglucan (EPS I) synthesis and nodule infection was determined. Four open reading frames (ORFs) were identified on this fragment. A mutational analysis revealed that these ORFs represent genes that were termed exoX, exoY, exoF, and exoQ. The locations of transposon insertions in these exo genes were determined at the nucleotide level. Plasmid integration mutagenesis revealed that the genes exoY, exoF, and exoQ are organized in an operon. The exoX gene running in opposite direction forms a monocistronic transcriptional unit. The exoX gene was shown to negatively influence the amount of EPS I synthesized. The exoY gene is coding for a membrane associated protein homologous to the C-terminal part of the Xanthomonas campestris glucosyltransferase GumD and the Salmonella typhimurium galactose transferase RfbP. ExoF, a probable periplasmatic protein, is nearly identical to the protein encoded by ORF1 of Rhizobium sp. strain NGR234. ExoQ is most probably a membrane associated protein as deduced by its hydrophobic structural features. All three genes of the exoYFQ operon were shown to be essential for succinoglucan synthesis and nodule infection. PMID- 8439671 TI - Electrophoretic karyotypes of Tilletia caries, T. controversa, and their F1 progeny: further evidence for conspecific status. AB - Electrophoretic karyotypes were obtained from intact sporidia and mycelia of Tilletia controversa and T. caries, and hybrid progeny were obtained by crossing these pathogens. The chromosomes typically ranged from approximately 850 to 4,490 kilobases (kb) for all strains, and they were variable in number with 19 or 20 for strains of T. controversa, 14-20 for T. caries, and from 19 to 22 for the hybrid progeny. The estimated genome size varied from 28 to 42 megabases (Mb) for these strains. Radiolabeled probes made of single copy DNA fragments and a heterologous actin gene identified four linkage groups among all strains that exhibited maximum chromosome length polymorphisms of 14% or less. The chromosomes carrying the rDNA genes, representing a fifth linkage group, exhibited length polymorphisms of approximately 40%. The actin gene and a rDNA probe hybridized with one or more bands in these strains, suggesting that some of the variability in chromosome number may result from aneuploidy. The karyotypes of the hybrid progeny revealed chromosome numbers and genome sizes essentially identical to each parental strain, clearly indicating that the reduction division stage of meiosis had occurred. These data and other corroborative genetic data provide substantial evidence that T. controversa and T. caries are not different species, but variants of a single species. PMID- 8439673 TI - In time, we will prevail. PMID- 8439672 TI - Molecular cloning and analysis of abundant and stage-specific mRNAs from Puccinia graminis. AB - To characterize highly expressed mRNAs from germinated urediniospores of Puccinia graminis f. sp. tritici, we isolated 68 cDNA clones of abundant mRNA species belonging to at least six homology groups. The two most abundant homology groups, HG1 and HG2, contained 54 of the 68 cDNA clones and accounted for 2.4 and 0.6% of the poly(A)+ RNA in germinated urediniospores, respectively. By sampling different developmental stages of the uredinial cycle, we showed that the uam transcript, corresponding to HG2, accumulated in all stages of hyphal and urediniospore development, whereas the accumulation of usp transcript, corresponding to HG1, was specific to the sporulation stage. Southern blot analysis indicated that usp is a small gene family consisting of three to four members. Sequence analysis of 10 cDNA clones indicated that two different members of the usp gene family were expressed in germinated urediniospores. This gene family encodes small hydrophobic polypeptides of 113 amino acids with an unusual amino acid composition, in that alanine, glycine, leucine, and proline represent 48% of the protein. These polypeptides are predicted to be localized extracellular because they contain a putative signal sequence and may be functionally related to hydrophobins, a family of small hydrophobic proteins abundantly expressed during sporulation in Schizophyllum commune and Aspergillus nidulans. The uam and usp genes deserve further investigation, including isolation of genomic clones. The regulatory regions of the uam gene, which is highly expressed in hyphae, may be useful in the construction of a transformation vector for rust fungi. PMID- 8439675 TI - Wearable artificial kidneys for continuous dialysis. A personal view. AB - Since 1971, the author has been actively promoting and working on a wearable artificial kidney for continuous dialysis. Such a kidney could allow the patient to have a more normal life style, eliminate treatment scheduling, and provide stable chemistries. Two partially successful wearable kidneys based upon hemofiltration have been devised. One required the patient to drink a liter of dialysate every hour to replace ultrafiltrate loss, and the other regenerated the ultrafiltrate with a REDY sorbent cartridge. Although the patients underwent anticoagulation, their hemofilters clotted in fewer than 5 days. In addition, there was a serious risk of bleeding in the event of accidental injuries. Use of a peritoneal access eliminates these blood related problems. Continuous ambulatory peritoneal dialysis (CAPD) is a successful continuously wearable kidney, but the bag changes are a chore. This drawback often produces technique failure, resulting in the patient shifting to hemodialysis. Regeneration of peritoneal dialysis has been performed successfully in intermittent peritoneal dialysis, but the higher concentration of protein in spent CAPD fluid interfered with performance of the sorbent cartridge. The author demonstrated that removing the protein by filtration through a hemofilter before regeneration resolves this problem, permitting development of a viable wearable kidney. PMID- 8439674 TI - Evolution of recombinant human erythropoietin usage in clinical practice in the United States. Is there an optimal way to use rHuEPO? PMID- 8439676 TI - Electronic control of pathologic tone disturbances in the larynx. AB - The complex anatomy of the larynx and the wide varieties of disturbances potentially affecting the tension of its constituent muscles give rise to various clinical presentations. Whatever the causes of pathologic tone disturbances affecting the larynx, rehabilitation should start by focusing on the dynamic adjustment of glottic tension in the muscles that have become separated from their respective central nervous system command centers. The objective of laryngeal rehabilitation is combined restoration of individual behaviors such that mutual, global relationships simulating those present before disability are reestablished. PMID- 8439677 TI - Performance optimization of left ventricular assistance. A computer model study. AB - Performance of temporary parallel left ventricular assistance was investigated and the theoretic conditions leading to optimal behavior of the mechanical system were explored. Computer models of nonpulsatile and pulsatile left ventricular assist devices (LVADs) were incorporated into a previously reported closed-loop simulation of the canine cardiovascular system. Assuming the assisted heart was capable of recovery, LVAD performance was assessed based on both myocardial oxygen balance and cardiac output. With a synchronous LVAD, and operating in a counterpulsation mode, these variables were sensitive to the phasing of pump ejection. Maximum reduction in cardiac oxygen consumption, maximum increase in oxygen availability, and maximum increase in cardiac output with the atrio-aortic device were obtained when pump ejection immediately followed aortic valve closure. These variables were directly proportional to the magnitude of bypass volume. The pulsatile asynchronous and nonpulsatile LVAD models affected oxygen balance in a similar manner, but neither performed so well as the synchronous model when equal bypass volumes were used. Ventricular uptake of blood provided a further 27% decrease in oxygen consumption and further 78% increase in oxygen availability than atrial uptake. In summary, the model predicted that the pulsatile synchronous LVAD, filling from the ventricle during heart systole and ejecting into either the ascending or descending aorta just after ventricular systole, would be most beneficial to both myocardial oxygen balance and cardiac output. PMID- 8439678 TI - Predictive performance of three methods of activated clotting time measurement in neonatal ECMO patients. AB - Previously reported activated clotting time (ACT) data in adults demonstrated higher values with the HemoTec LRACT (HT) and TriMed ACTivator (TM) techniques than with the Hemochron System P214/215 (HC) technique throughout a range of heparin concentrations. This study sought to determine if a difference exists in ACT values of neonatal patients receiving ECMO. ACTs were performed in nine neonatal ECMO patients using the HC, HT, and TM techniques. Techniques were compared for positive or negative direction of any prediction difference (bias), and the typical value of a difference (precision). Simultaneous, duplicate, morning, and afternoon ACT comparisons were obtained using all three techniques. Forty-six comparisons of HC values in the 180-240 sec range were analyzed. All techniques produced results different from the same sample. The HT and TM techniques were upwardly biased by 51 and 148 sec, respectively, when evaluated against HC. HT was negatively biased by 123 sec when evaluated against TM. Because ACT values vary among techniques, ACT target ranges should be technique specific. Future references to ACT data should identify the equipment and procedures employed. PMID- 8439679 TI - Coagulation patterns in bovine left heart bypass with phospholipid versus heparin surface coating. AB - The current study was designed to evaluate tubing sets with either polymeric phospholipids or ionically bound heparin in six bovine experiments (body weight, 70 +/- 5 kg). No heparin was given systemically. Left heart bypass was started with 300 ml of clear priming solution and maintained over 6 hours (50 ml/kg/min). Coagulation studies included platelet counts, activated coagulation time (ACT), thrombin time (TT), fibrinogen (Factor I), antithrombin III (AT III), and fibrinopeptide A (FPA). Normalized platelet levels dropped from 100 +/- 12% before to 86 +/- 13% after 6 hours of left heart bypass for heparin, compared with 100 +/- 46% to 90 +/- 44% for phospholipid coating (NS). The ACT increased from 146 +/- 7 sec at 10 min to 159 +/- 16 sec after 6 hours for heparin, compared with 122 +/- 4 to 126 +/- 5 sec for phospholipid (p < 0.05). Thrombin time changed from 18 +/- 0 sec before to 19 +/- 1 sec after 6 hours for heparin, as compared with 16 +/- 1 sec to 18 +/- 1 sec for phospholipid (NS). Factor I levels decreased from 1.5 +/- 0.3 g/L to 1.3 +/- 0.1 g/L for heparin, compared with 1.5 +/- 0.2 g/L to 1.4 +/- 0.3 g/L for phospholipid. Antithrombin III levels changed from 102 +/- 26% to 91 +/- 7% for heparin, compared with 123 +/- 12% to 118 +/- 12% for phospholipid. Fibrinopeptide A levels changed from 100 +/- 60% to 130 +/- 13% for heparin, compared with 100 +/- 11% to 99 +/- 6% for phospholipid (P < 0.05). No macroscopic red clots were found in either group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8439680 TI - Intermediate-term outcome of renal retransplants in the cyclosporine era. AB - To determine the influence of selected parameters on intermediate-term outcome of renal retransplants, univariate and multiple regression analyses were performed on all 100 consecutive cyclosporine treated retransplants performed between 1984 and 1990 (mean follow up, 4.6 +/- 2.3 years). Actual 1 year and actuarial 5 year graft survivals were higher in living compared with cadaver donor transplants (84% and 79% vs 69% and 56%, respectively; p < 0.05). Among cadaver donor transplant recipients, allografts with immediate early function had better 1 and 5 year graft survivals when compared with those with delayed function (81% and 62% vs 59% and 38%, respectively; p < 0.05). Recipients with acute rejection had inferior 1 year and 5 year graft survivals when compared with rejection free patients (65% and 35% vs 80% and 57%, respectively; p < 0.05). Graft survival time of primary transplants was also a significant predictor of retransplant outcome with 1 and 5 year graft survivals of 50% and 36%, respectively, in patients in whom primary grafts survived less than 3 months, compared with 75% and 58% in those in whom grafts survived longer than 3 months (p < 0.05). Recipient age, race, renal disease, and levels of panel reactive antibodies had no effect on intermediate-term outcome. In a multiple regression analysis, delayed graft function, acute rejection, and primary graft survival time less than 3 months correlated inversely with long-term survival of retransplants (multiple r = 0.65). A total of 39 grafts were lost due to rejection (22), sepsis (6), graft nonfunction (5), death with a functioning graft (4), noncompliance (1), and recurrent renal disease (1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8439681 TI - Erythrocytosis after renal transplantation. A prospective analysis. AB - A prospective analysis of all cyclosporine treated renal transplants performed between 1987 and 1990 was performed to determine the incidence and etiologic factors of post transplant erythrocytosis (PTE) and its effect on short-term outcome. PTE developed in 25 (8.1%) recipients (mean age, 41 +/- 10 years). PTE occurred more frequently in men (12.8%) than women (1.6%) (p < 0.001), diabetic patients (22.9%) than nondiabetic patients (6.2%) (p < 0.001), and rejection-free recipients (11%) compared with those with early rejection (4%) (p < 0.05) but was independent of recipient race and donor source. Sixteen patients in whom PTE subsequently developed had pretransplant hematocrits above 30%. PTE occurred most frequently in the first year posttransplant (range, 2-29 months). Serum erythropoietin levels were inappropriately elevated in all patients (mean, 24 +/- 2.2 mU/ml), but serum iron, folate, and B12 levels were all normal. Mean serum creatinine and creatinine clearance were 1.7 +/- 0.5 mg/dl and 58 +/- 20 ml/min, respectively. Twenty-three patients underwent phlebotomy (mean, 3.5 +/- 0.5 units) and six had PTE-related complications. In 14 patients, PTE persisted with hematocrit of 53 +/- 1.5% (range, 51-56) compared with 57 +/- 2.6% (range, 54-64) at the time of PTE onset. In conclusion, PTE occurs primarily in the first year posttransplant and is characterized by inappropriate elevation of erythropoietin. Predictors for PTE include male gender, diabetes mellitus, pretransplant hematocrit above 30%, absence of rejection, and excellent renal allograft function. PMID- 8439682 TI - An electric model with time varying resistance for a pneumatic membrane blood pump. AB - To investigate the effects of an artificial heart and cardiac assist device on the cardiovascular system and determine the proper control method, an electrical model is an effective tool. An electric model with time varying resistance is proposed to represent a pneumatic membrane blood pump, by which the resistance of the valves in the pump is a function of time. The model is consistent over the whole cardiac cycle, and the important transitional processes between systole and diastole are considered. The calculated results based on this model are compared with the experimentally measured waveforms of the corresponding state-variables of a loaded pump, and the model parameters estimated using the least-squares criterion are compared with the measured physical values of corresponding functional parts. Results showed that this electric model is capable of representing a pneumatic membrane pump with quite satisfactory accuracy. They also showed that the transitional property of the valve resistance has a significant influence on the output characteristics of the pump. PMID- 8439683 TI - The Moncrief-Popovich catheter. A new peritoneal access technique for patients on peritoneal dialysis. AB - Existing catheter implantation techniques violate a fundamental premise of wound healing. The immediate presence of the catheter in the post operative surgical wound forms a passage for permanent colonization of the catheter tunnel and cuff(s). This is manifested by the almost universal presence of the biologic products of bacterial growth (biofilm) on the external and internal surfaces of these catheters. The Moncrief-Popovich catheter and implantation technique are designed to address this problem. The Moncrief-Popovich catheter is implanted in the standard fashion, except that the external segment of the catheter is buried subcutaneously at the time of implantation. After allowing 3-5 weeks for tissue in-growth in a sterile environment, a small incision is made in the skin through which the external segment of the catheter is exteriorized and attached to an adapter. A 2 year trial was conducted in 59 patients, comprising 530 patient months of experience; the incidence of peritonitis was one episode for every 29.4 patient months. All but three of the patients used the standard spike exchange technique. In a recently initiated study using disconnect procedures in 63 of the 74 patients studied, the peritonitis rate was one episode for every 28.7 patient months; patient-months have totalled 201.2 to date. There was a rate of one exit site infection every 12.57 patients-months. It was concluded that the Moncrief Popovich catheter and implantation technique result in a substantial decrease in the incidence of peritonitis for patients using the standard spike exchange system. PMID- 8439684 TI - Peritoneal transfer during maximal hyperosmotic ultrafiltration in the rat. AB - Peritoneal transfer parameters were estimated in rats (n = 24) while maximal net ultrafiltration rate (nUFR) was achieved with 15% dextrose dialysis solution (1,153 mOsm/kg) and compared with those obtained with 0.37% dextrose solution (301 mOsm/kg). Experiments were carried out with dialysis solutions of pH approximately 6.5 and approximately 7.6, respectively, for 15% dextrose dialysis solution and 0.37% dextrose solution. Increases in both convective and diffusive transfer resulted in more than 70% greater peritoneal clearances of urea, potassium, and phosphate with hyperosmotic solutions at both pH values. Protein removal was increased only with a hyperosmotic solution of pH approximately 6.5 compared with isosmotic conditions at the same pH. Results support the hypothesis that increased peritoneal transfer parameters under hyperosmotic conditions depend not only upon enhanced convection but also on factors promoting diffusive transfer. PMID- 8439685 TI - Fundamental rhythm of sympathetic nerve discharge in animals with total artificial hearts. PMID- 8439686 TI - Plasma amino acids in patients with acute nonlymphocytic leukemia receiving parenteral nutrition. AB - OBJECTIVE: To assess the effect of parenteral amino acid solutions on plasma amino acid concentrations in patients with acute nonlymphocytic leukemia (ANLL) receiving parenteral nutrition (PN). DESIGN: Ten patients were studied at diagnosis, on the morning PN was started, and three times during PN therapy coinciding with the sequential administration of three different amino acid solutions (Aminosyn, FreAmine HBC, and TrophAmine). The order of amino acid solution administration in each patient was by a randomized, block design. RESULTS: The patients were undergoing identical intensive induction therapy. There was no significant difference in the number of days they received PN or the amount of protein or calories received during the three PN study periods. At diagnosis, phenylalanine and glutamic acid concentrations were elevated compared with previously published normal values and remained elevated at all observation times. During PN, asparagine, aspartic acid, and tyrosine concentrations were significantly lower with all three amino acid solutions compared with their concentrations at diagnosis. Glycine and threonine concentrations were also significantly lower with FreAmine HBC and TrophAmine administration and cysteine concentrations were significantly lower with FreAmine HBC administration than at the time of diagnosis. Aminosyn was associated with plasma amino acid concentrations most similar to those measured at diagnosis. CONCLUSIONS: These results indicate that most amino acid concentrations fall within the normal range at diagnosis in the ANLL patients studied. Plasma concentrations for certain amino acids can be influenced by the amino acid solution used in PN. Further understanding of the derangements in amino acid metabolism and the influence of parenterally administered amino acid solutions on plasma amino acid concentrations may lead to improvements in the nutritional support of cancer patients. PMID- 8439687 TI - Population pharmacokinetics: development of a medical intensive care unit specific gentamicin dosing nomogram. AB - OBJECTIVE: This study was designed to develop a population-specific dosing nomogram for gentamicin in medical intensive care unit (MICU) patients using the population pharmacokinetic program nonparametric expectation maximization (NPEM). DESIGN: Observational clinical gentamicin dosing data were collected, entered into the USC*PACK database program PASTRX, and downloaded into the population pharmacokinetic program NPEM. NPEM generated population pharmacokinetic parameter values that were used to develop a gentamicin dosing nomogram. The nomogram was tested in the next 15 patients admitted to MICU to determine accuracy. Doses given per the MICU and the Hull-Sarubbi nomograms were compared with doses based on actual patient-specific pharmacokinetic parameter values. Reliability coefficients (intraclass correlation coefficients) were calculated to assess the agreement between observations. SETTING: Data were gathered from patients receiving gentamicin therapy in the MICU, Presbyterian University Hospital, Pittsburgh. PATIENTS: Baseline population pharmacokinetic parameter values were determined in 36 MICU patients receiving gentamicin therapy. Patients with renal failure receiving hemodialysis or another mechanical method of blood clearance or fluid removal were excluded. The population parameter values in the form of a dosing nomogram were then used prospectively to dose gentamicin in 15 patients. RESULTS: NPEM generated population parameter values similar to those previously published using the Sawchuk-Zaske method in ICU patients. The mean volume of distribution generated using NPEM was 0.34 +/- 0.12 L/kg. The relationship between creatinine clearance (Clcr) and elimination rate constant (Ke) was: Ke = 0.00218 x Clcr + 0.007. The nomogram-derived doses correlated with doses determined by using actual patient-specific pharmacokinetic values (p < 0.05). The Hull-Sarubbi derived doses, however, did not correlate with patient-specific doses (p > 0.05). Only one patient had a peak concentration < 6 mg/L. Two of 15 patients had trough concentrations prior to the first maintenance dose > 2 mg/L. CONCLUSIONS: The use of NPEM to generate population-specific pharmacokinetic parameter values has been previously described. Application of population specific dosing nomograms can improve initial dosing regimens such that conventional therapeutic concentrations can be achieved early in therapy. This nomogram, however, does not preclude follow-up patient-specific pharmacokinetic analysis. PMID- 8439688 TI - Pharmacy-enforced outpatient drug treatment protocols: a case study of Medi-Cal restrictions for cefaclor. AB - OBJECTIVE: To evaluate whether a pharmacy-enforced treatment protocol successfully limited the use of a high-cost medication to high-risk patients. DESIGN: A case study cost-effectiveness analysis was conducted to evaluate a treatment protocol for cefaclor. Episodes of care were defined, healthcare expenditures for all services were aggregated, and demographic data were retrieved from a five percent random sample of California Medicaid (Medi-Cal) recipients. Data were available for episodes occurring before cefaclor was made available under Medi-Cal. SETTING: Medi-Cal added cefaclor to its formulary, limiting its use to patients over 50 years of age with lower respiratory tract infections (LRTIs). The unit of analysis was an episode of outpatient antibiotic treatment. PATIENTS: Confirmed LRTI episodes and unconfirmed LRTI cefaclor episodes were analyzed, including multiple episodes of treatment for individual patients. A total of 7855 non-cefaclor LRTI episodes and 2556 cefaclor episodes were analyzed. MAIN OUTCOME MEASURES: The primary outcome measures were healthcare expenditures three months after the initiation of antibiotic therapy, differentiated by type of service. RESULTS: Physicians directed cefaclor toward higher-risk patients over age 50 years, even in unconfirmed LRTI episodes. Cefaclor use was estimated to reduce posttreatment costs by $388 per patient (p < 0.001), primarily because of reduced hospital expenditures of $366 (p < 0.001). CONCLUSIONS: Pharmacy-enforced outpatient drug treatment protocols may be a viable alternative to restrictive formularies and prior authorization. In the case of cefaclor, the Medi-Cal treatment protocol appeared to allow high-risk patients better access to a high-cost medication while reducing total posttreatment costs. PMID- 8439689 TI - Inappropriate use of high-dose glyburide to treat uncontrolled type 2 diabetes mellitus. AB - OBJECTIVE: To report a case of chronic glyburide overdose. CASE SUMMARY: A patient with noninsulin-dependent diabetes mellitus (NIDDM) who had previously developed secondary failure while taking a maximal dosage of glipizide was switched to glyburide 5 mg/d. The patient initially experienced adequate glycemic control while taking glyburide, but subsequently experienced deterioration in glycemic control. This necessitated gradual increases in the dosage of glyburide until the maximum dosage of 20 mg/d was reached. Because the patient's diabetic control did not improve with this dosage of glyburide, she decided independently to increase the dosage further. She ingested an average daily dose of 37.7 mg of glyburide over the 18 days that preceded her clinic visit without experiencing any glyburide-related adverse effects. DISCUSSION: Progression of NIDDM may be responsible for the development of secondary sulfonylurea failure in NIDDM patients treated with oral sulfonylurea drugs. Consequently, these patients should be treated as patients dependent on insulin. CONCLUSIONS: NIDDM patients treated with oral sulfonylurea drugs require long-term blood glucose monitoring to detect the development of secondary sulfonylurea failure. Patients who experience secondary failure to a particular sulfonylurea drug do not appear to develop long-term blood glucose control when switched to a different oral sulfonylurea drug. These patients should be treated with insulin therapy. PMID- 8439690 TI - Isoniazid-associated psychosis: case report and review of the literature. AB - OBJECTIVE: To describe a case of isoniazid-associated psychosis and review the incidence of this adverse effect. DATA SOURCES: Information about the patient was obtained from the medical chart. A MEDLINE search of the English-language literature published from 1950 to 1992 was conducted and Index Medicus was manually searched for current information. STUDY SELECTION: All case reports describing isoniazid-associated psychosis were reviewed. DATA EXTRACTION: Studies were evaluated for the use of isoniazid, symptoms of psychosis, onset of symptoms, and dosage of isoniazid. DATA SYNTHESIS: The case report is compared with others reported in the literature. The incidence of isoniazid-associated psychosis is rare. CONCLUSIONS: The mechanism of isoniazid-associated psychosis is uncertain. It appears that isoniazid was associated with the psychosis evident in our patient and in the cases reviewed. PMID- 8439691 TI - Suspected nafcillin-induced interstitial nephritis. AB - OBJECTIVE: To present a case of nafcillin-induced interstitial nephritis. METHODOLOGY: Case report and literature review. SETTING: Hospital. RESULTS: Three days following initiation of nafcillin therapy for staphylococcal pneumonia, an 80-year-old woman developed allergic manifestations and progressive renal impairment suggestive of acute allergic interstitial nephritis. These manifestations were completely reversed within 96 hours of cessation of nafcillin therapy. CONCLUSIONS: In the clinical setting of acute renal failure in a patient on nafcillin therapy, acute interstitial nephritis should be considered. Prompt cessation of nafcillin therapy has generally been associated with reversal of symptoms and an improvement in renal function. PMID- 8439692 TI - Hypersensitivity reactions associated with parenteral nutrition: case report and review of the literature. AB - OBJECTIVE: To report a case of hypersensitivity reaction to total parenteral nutrition (TPN) and to review the available literature on this rare adverse effect. CASE SUMMARY: The reaction occurred in a 52-year-old woman with pancreatic carcinoma who received intravenous metronidazole, tobramycin, vancomycin, ranitidine, morphine, TPN, and lipid emulsion postoperatively. Within 30 minutes of starting the TPN and lipid emulsion, the patient complained of dyspnea and pruritus. She began hyperventilating and was hypoxic. The reaction resolved after discontinuation of the TPN and lipid emulsion. The reaction recurred when lipid-free TPN was initiated on two subsequent occasions, and resolved spontaneously following the discontinuation of the lipid-free TPN. The antibiotics, ranitidine, and morphine therapy were continued with no further adverse effects and the patient was discharged on postoperative day 17. DISCUSSION: Case reports in the literature on TPN-related hypersensitivity reactions were reviewed. It was speculated that the multivitamin preparation (MVI) may have been the causative agent in our patient; however, this was not confirmed by MVI-free TPN administration or by epicutaneous allergy testing. CONCLUSIONS: Hypersensitivity reactions to TPN can be managed by withholding the TPN and treating with antihistamines if needed until the reaction resolves. Identification, possibly by epicutaneous allergy testing, and removal of the offending agent(s) from the TPN is necessary if TPN therapy must be restarted. PMID- 8439693 TI - Retroperitoneal abscess caused by Mycobacterium chelonae and treatment. AB - OBJECTIVE: To report a case of retroperitoneal abscess caused by Mycobacterium chelonae and treatment. DESIGN: Case report. SETTING: Private community teaching hospital. PATIENTS: A patient was admitted to the hospital following a gunshot to the flank. The bullet passed through the iliac crest and lodged in the abdomen. INTERVENTION: The patient was treated with cefazolin, trimethoprim/sulfamethoxazole, and amikacin at different times. OUTCOME: The patient responded well to pharmacologic treatment and at 18-month follow-up, he is disease free. CONCLUSIONS: Antimicrobial agents with in vitro activity against M. chelonae, especially amikacin-containing regimens, are recommended for treating M. chelonae infection. PMID- 8439694 TI - Labetalol: response and safety in critically ill hemorrhagic stroke patients. AB - OBJECTIVE: To observe and characterize the blood pressure (BP)-lowering and adverse hemodynamic and/or central nervous system effects of intravenous bolus doses of labetalol in hemorrhagic stroke patients. DESIGN: Observational, prospective, pilot survey conducted over an eight-week period. SETTING: Surgical intensive care unit. PARTICIPANTS: Patients admitted with an intracerebral or subarachnoid hemorrhage. MAIN OUTCOME PARAMETERS: Absolute decline in systolic BP (SBP) and diastolic BP (DBP), time to peak reduction in SBP and DBP, and adverse hemodynamic and mental status changes. RESULTS: Labetalol at doses between 5 and 25 mg lowered SBP by 6-19 percent (baseline 152-184 mm Hg) and DBP by 3-26 percent (baseline 50-99 mm Hg). Adverse hemodynamic or mental status changes were not detected following labetalol administration. CONCLUSIONS: Small (< or = 25 mg) intravenous bolus doses of labetalol produce mild decreases in BP in hemorrhagic stroke patients. PMID- 8439695 TI - Use of clonidine to treat hot flashes secondary to leuprolide or goserelin. AB - OBJECTIVE: To determine the effects of clonidine, a centrally acting adrenergic agonist, in abating symptoms of hot flashes in men receiving either leuprolide or goserelin for prostate cancer. DESIGN: Patients were administered transdermal or oral clonidine 0.1-0.2 mg/d. Dosages were increased in increments of 0.1-0.3 mg/d every two to four weeks if symptoms persisted or until adverse effects developed. SETTING: Medical oncology clinic at the University of Illinois and the hypertension clinic at the Veterans Affairs West Side Medical Center. PARTICIPANTS: Consenting male patients were eligible for the study if they were receiving leuprolide or goserelin for prostate cancer and were experiencing hot flashes. Exclusion criteria included diastolic blood pressure of 75 mm Hg or below or a history of adverse reactions to clonidine. MAIN OUTCOME MEASURES: Effectiveness of clonidine was determined by questioning patients about frequency, severity, and duration of hot flashes at baseline and at two- to four week intervals. RESULTS: All four patients receiving clonidine experienced a partial response within two weeks of starting treatment. No dose-dependent response was observed. Adverse effects were noted in one patient but did not result in discontinuation. CONCLUSIONS: Our results document the first report of the use of clonidine to treat hot flashes secondary to leuprolide or goserelin therapy. Symptomatic improvement was noted in all four patients. Further evaluation of clonidine as well as other centrally acting adrenergic agonists is needed. PMID- 8439696 TI - Nurses' performance of inhalation technique with metered-dose inhaler plus spacer device. AB - OBJECTIVE: To determine if nurses could correctly use a metered-dose inhaler plus spacer (MDI-spacer) device after a brief description and demonstration of proper use by a clinical pharmacist. DESIGN: Pretest, educational intervention, posttest. SETTING: University hospital. PARTICIPANTS: Twenty-three nurses. INTERVENTIONS: Nurses were asked to use the MDI-spacer (Aerochamber) and were scored using a nine-point checklist (pretest). Educational intervention by the clinical pharmacist consisted of a five-minute discussion and correct demonstration of the device. Nurses were then asked to use the device again (posttest). MAIN OUTCOME MEASURES: Pre- and posttest scores. RESULTS: Total scores were improved after the educational intervention (66 percent pretest vs. 88 percent posttest, p = 0.0001). In an item analysis, four of the nine steps had improved significantly. CONCLUSIONS: A brief discussion and demonstration of correct use of MDI-spacers is effective in improving nurses' skill in using the device. PMID- 8439697 TI - Ondansetron for postoperative nausea and vomiting. PMID- 8439698 TI - Isoproterenol treatment of torsades de pointes. PMID- 8439699 TI - Vigabatrin. AB - OBJECTIVE: To introduce the reader to the use of a new agent, vigabatrin, in the treatment of refractory complex partial seizures. Clinical trials and pharmacokinetic data are reviewed, as well as neuropathology, adverse effects, drug interactions, and dosage guidelines. DATA SOURCES: A MEDLINE search through March 1992 was used to identify pertinent English-language literature, including clinical trials, reviews, abstracts, and conference proceedings. Indexing terms included vigabatrin and anticonvulsants. STUDY SELECTIONS: All clinical trials (total of 21) were reviewed, as were all pharmacokinetic studies (total of 8). Selected studies highlighting chemistry, pharmacology, neuropathology, and adverse effects were also reviewed. DATA EXTRACTION: Performed subjectively by the author. Trials were assessed by design, sample size, types of seizures of the subjects, and clinical response. DATA SYNTHESIS: Vigabatrin represents the first of a new class of antiepileptic drugs (AEDs)--the gamma-aminobutyric acid transaminase (GABA-T) inhibitors. Vigabatrin works by selective, irreversible inhibition of GABA-T, thus preventing the breakdown of GABA. It has been shown to produce dose-dependent increases in cerebrospinal fluid GABA concentrations, and decreases in GABA-T activity. Vigabatrin may also cause a decrease in excitation related amino acids. It is well absorbed, is not protein bound, and is eliminated by glomerular filtration. However, even with a short half-life (5-7 h), vigabatrin may be given once or twice daily because of its mechanism of action. Few drug interactions have been reported with this agent, although decreases in phenytoin concentration may reach clinical significance. Concern over neuropathologic findings (microvacuolization of white matter) in animals caused trials of vigabatrin to be halted in 1983, but trials have now resumed as there is no evidence of toxicity in humans. Clinical efficacy of vigabatrin has been evaluated in controlled trials and appears to be most effective in complex partial seizures, producing a 50 percent or greater reduction in seizure frequency in approximately 50 percent of the adult patients studied. Efficacy in children with partial seizures also appears promising, and one uncontrolled study suggests that further study of vigabatrin in infantile spasms may be warranted. CONCLUSIONS: Vigabatrin appears to be effective in treating refractory complex partial seizures in adults and refractory partial seizures in children. Its relatively benign adverse-effect profile and few known drug interactions may given this agent an advantage over existing anticonvulsants. However, definitive conclusions about the role of vigabatrin in epilepsy treatment should await the completion of ongoing Phase II and Phase III trials. PMID- 8439700 TI - Renal functional alterations induced by angiotensin-converting enzyme inhibitors in heart failure. AB - OBJECTIVE: To review the effects of angiotensin-converting enzyme (ACE) inhibitors on renal pathophysiology and the compensatory mechanisms involved in heart failure. A clinical application of the use of these agents in the setting of concomitant heart failure and renal insufficiency also is presented. DATA SOURCES: A MEDLINE search was conducted using the terms heart failure, congestive; renal insufficiency; and angiotensin-converting enzyme inhibitors. STUDY SELECTION: All applicable animal and human trials were reviewed. DATA SYNTHESIS: Advances in the management of heart failure have led to new insights into the complex pathophysiology of this condition, particularly the favorable clinical effects noted with the ACE inhibitors. The net effect of ACE inhibitors on the renin-angiotensin system in patients with heart failure is to augment renal blood flow to a greater extent than cardiac output. Glomerular filtration rate is either unchanged or decreased by ACE inhibition. Sodium excretion is augmented primarily by alterations in glomerular hemodynamic parameters. ACE inhibitors may alter renal tubular function, both directly and indirectly, leading to increased diuresis and natriuresis. CONCLUSIONS: Although ACE inhibitors exert beneficial pharmacodynamic effects on the renal bed in patients with heart failure, clinical consideration of volume and neurohormonal status prior to institution of therapy is prudent. PMID- 8439701 TI - Use of trans-retinoic acid in the treatment of acute promyelocytic leukemia. AB - OBJECTIVE: To discuss acute promyelocytic leukemia (APL) and review the literature concerning differentiation treatment of APL with trans-retinoic acid (t-RA). DATA SOURCES: English-language articles concerning APL or its treatment with t-RA were identified with a MEDLINE search. STUDY SELECTION: All studies available at the time of article preparation, which addressed t-RA treatment in APL, were selected. DATA EXTRACTION: Data extraction and assessment were performed subjectively by the authors. An extensive discussion of specific study details is included in the article. DATA SYNTHESIS: APL is a unique subset of acute myelogenous leukemia and is typified by an accumulation of malignant promyelocytes in the bone marrow. Within the granulocyte cell cycle of a patient with APL, differentiation has been halted at the level of the promyelocyte, preventing formation of mature granulocytes. Upon treatment with traditional cytotoxic chemotherapy, complete remission rates of approximately 70 percent, with a five-year survival ranging from 25 to 40 percent have been achieved. In most patients with APL, a characteristic chromosomal t(15q+;17q-) translocation has been found, which may be responsible for the production of an aberrant retinoic acid receptor-alpha. Therefore, t-RA induction therapy has been investigated and has produced promising results. Administration of t-RA in dosages of 45-100 mg/m2/d has induced complete remissions. The apparent mechanism of t-RA is the induction of promyelocyte differentiation and maturation. The most common adverse effects noted have been dry skin, cheilitis, and headaches. CONCLUSIONS: Upon consideration of the initial trials, t-RA appears to be a promising and unique treatment for APL. PMID- 8439702 TI - Assessing the quality of pharmaceutical care. II. Application of concepts of quality assessment from medical care. AB - OBJECTIVE: To present a framework that facilitates quality assessment of pharmaceutical care (PC) so that the profession and the public may identify pharmacists in ambulatory settings who provide quality care in all aspects of the their practices. DATA SOURCES: A MEDLINE search augmented by a review of International Pharmacy Abstracts was used to identify pertinent quality assessment and pharmacy practice literature; indexing terms included quality assurance, healthcare, pharmacists, community pharmacy services, ambulatory, pharmacy, and process and outcome assessment. STUDY SELECTION: All identified quality assessments of community pharmacy practice were considered. Studies that documented the effectiveness of specific pharmacist activities and patient satisfaction were also included. DATA EXTRACTION: The literature was independently reviewed by the primary author. DATA SYNTHESIS: The structure process-outcome paradigm is presented as a framework for quality assessment of PC. Structure should be assessed at periodic intervals because it identifies the potential for the provision of quality care. Process, the care that pharmacists provide, must be documented and linked to outcomes before either structure or process can be used to make inferences about the quality of PC. Technical and interpersonal processes should be examined. Outcomes require an interdisciplinary approach that not only considers other medical care inputs but also recognizes the psychologic, economic, and social factors that affect health status and quality of life. Process and outcome must both be assessed to distinguish the contribution of pharmacists from that of other healthcare providers. Examples of criteria are provided and a model to integrate PC within the healthcare system is discussed. CONCLUSIONS: It is pharmacists' duty to ensure that patients receive an acceptable level of PC. The structure-process-outcome paradigm provides a framework to identify and link pharmacists' processes with patients' outcomes. PMID- 8439703 TI - Vancomycin and tobramycin clearance in an infant during continuous hemofiltration. AB - OBJECTIVE: To report a case of vancomycin and tobramycin clearance by continuous veno-venous hemofiltration in an infant. Hemofiltration clearance (ClHF) was calculated by two methods and compared for ease and reliability. METHODOLOGY: Case report of a hospitalized four-month-old infant. With method A, ClHF calculation for vancomycin and tobramycin was determined by accurate collection of ultrafiltrate in five 24-hour periods and a midpoint serum sample. With method B, ClHF calculation was determined by obtaining prefilter sample, postfilter sample, and blood flow through filter (Fick principle) over three study periods, correlating to three of five study periods in method A. RESULTS: The infant received continuous veno-venous hemofiltration. With method A, vancomycin ClHF ranged from 0.27 to 0.80 mL/min; tobramycin ClHF ranged from 0.32 to 0.91 mL/min. With method B, ClHF for vancomycin ranged from 0 to 2.08 mL/min. Tobramycin ClHF ranged from 0 to 1.6 mL/min when calculated with method B. CONCLUSIONS: Continuous veno-venous hemofiltration increased the clearance of vancomycin and tobramycin requiring dosage modifications. It appears that method A, which uses the ultrafiltration concentration compared with the serum concentration is more accurate than method B, as it averages fluctuations in ultrafiltrate flow rates. Method B compares a single pre- to postfilter drug concentration and relies on an accurate measurement of ultrafiltration flow rate. Determining ClHF based upon one point in time may overestimate ClHF when the ultrafiltration flow rate varies, as it does in the critically ill. Daily serum concentrations for vancomycin and tobramycin are recommended during continuous veno-venous hemofiltration. PMID- 8439704 TI - Acyclovir pH--possible cause of extravasation tissue injury. PMID- 8439705 TI - Effectiveness of bumetanide with low-dosage dopamine for diuresis. PMID- 8439706 TI - Ventricular fibrillation and anoxic encephalopathy secondary to astemizole overdose. PMID- 8439707 TI - Comment: profuse diarrhea after misoprostol use in Crohn's disease. PMID- 8439708 TI - Approaches to characterize protein-DNA interactions in vivo. AB - With the availability of direct genomic footprinting techniques the study of native genomes has been greatly facilitated. This review provides an overview of the techniques involved and gives also a description of the mode of action of different DNA modifying agents which can be used for such methods. These include exonuclease III, deoxyribonuclease, DNase I, micrococcal nuclease, dimethyl sulfate, diethyl sulfate, ethyl methanesulphonate, ethylnitrosourea, diethylpyrocarbonate, bromoacetaldehyde, potassium permanganate, osmium tetroxide, methidiumpropyl-EDTA-iron(II), formaldehyde, psoralen, 1,10 phenanthroline-copper and UV light. We also describe the limitations of the currently existing techniques and give some potential developments. PMID- 8439709 TI - Regulatory role of osteogenic growth polypeptides in bone formation and hemopoiesis. AB - Osteogenic growth polypeptides such as the osteogenic growth peptide (OGP), fragments of the parathyroid hormone (PTH), and insulin-like growth factors (IGF) regulate bone cell activity in vitro and may affect in vivo osteoblastic functions in an autocrine, paracrine, or endocrine manner. Several growth polypeptides capable of regulating osteogenesis circulate in the blood in an inactive form, complexed to parent molecules or binding proteins. During postablation bone marrow regeneration these factors may be activated, released from the blood clot, and together with locally produced polypeptides mediate the initial intramedullary/systemic osteogenic phase of this process. Then osteogenic growth polypeptides expressed by osteoblasts and other stromal cells have the potential to promote the second phase of regeneration that consists of osteoclastogenesis, resorption of the transient intramedullary bone, and hemopoiesis. This is probably an indirect effect inasmuch as these polypeptides can regulate the stromal cell expression of hemopoietic factors such as macrophage colony stimulating factor (M-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin 6 (IL-6), and the stem cell factor (SCF). The postablation marrow regeneration model is suitable for studying the expression and activity of osteogenic growth polypeptides and already has been used to assess the effect of aging on these parameters. Clinically, the osteogenic growth polypeptides and marrow regeneration have a potential role in osteoporosis therapy, implant and corrective bone surgery, and bone marrow transplantation. PMID- 8439710 TI - Results of interspinous segmental instrumentation in the sagittal plane. AB - There is concern that distraction instrumentation with segmental interspinous wiring (ISSI) might flatten the sagittal curves. We studied 110 cases of idiopathic scoliosis treated with ISSI with an average follow-up of > 2 years. The coronal deformity averaged 53 degrees preoperatively with a 58% average correction. For the entire group, the average preoperative thoracic kyphosis was 34 degrees and 32 degrees at follow-up. Children, however, gained an average of 4 degrees of thoracic kyphosis. Children wired to both rods gained 10 degrees in thoracic kyphosis. Preoperative lumbar lordosis was 45 degrees and 42.5 degrees at follow-up. There were five wire breakages in four patients, without loss of correction. There was one deep and one superficial infection and one dysesthesia that resolved. There were no cases of rod failure or pseudarthrosis. ISSI with careful rod contouring can maintain sagittal curves. In children, small improvements in the hypokyphotic spinal deformity can be achieved. PMID- 8439711 TI - Secondary axes activity of normal subjects and low back pain patients. AB - The purpose of this study was to compare the secondary axes activity of normal subjects and low back pain patients. Each subject performed maximum isometric trials in all six primary directions. This was followed by five dynamic repetitions in each of the cardinal planes against relative resistances set at 50% of the recorded maximum isometric torques for each axis. The results showed that for all movement axes the secondary axes torques were significantly less (p = 0.01-0.001) for low back pain patients compared to normal subjects. The secondary axes torques were generally weakly related to an individual's ability to both generate maximum isometric torques about the same axis and the primary axes maximum velocities. PMID- 8439712 TI - Spinal instrumentation for metastatic disease: in vitro biomechanical analysis. AB - A calf spine corpectomy model was employed to compare the ability of various spinal instrumentation techniques to restore stability after destruction of the anterior and middle columns. The constructs tested were an intact specimen, a Harms titanium cage, a cross-linked rectangular anterior Texas Scottish Rite Hospital construct, posterior segmental Luque rods combined with a cross-linked rectangular anterior TSRH construct, posterior Luque rods alone, cross-linked posterior Luque rods, and posterior Luque rods embedded in polymethyl methacrylate (PMMA). When compared to the intact state, only the combined anterior/posterior construct and the anterior TSRH construct were able to restore axial, sagittal, and torsional stiffnesses to levels equal to or higher than control levels. Embedding Luque rods in PMMA provided greater stiffness than either Luque rods alone or cross-linked Luque rods. If the anterior and middle columns of the spine are incompetent, as frequently occurs with metastatic disease, the goal of surgical treatment is to restore spinal stability while decompressing the neural elements. Either anterior or posterior techniques may be used. The findings of this study imply that commonly used spinal instrumentation constructs differ in their ability to restore axial, sagittal, and torsional stiffnesses to normal levels. PMID- 8439713 TI - A randomized double-blind trial of dextrose-glycerine-phenol injections for chronic, low back pain. AB - This randomized clinical trial evaluated the efficacy of injections of a dextrose glycerine-phenol connective tissue proliferant into the posterior ligaments, fascia, and joint capsules to treat chronic low back pain. Seventy-nine patients with chronic low back pain that had failed to respond to previous conservative care were randomly assigned to receive a double-blind series of six injections at weekly intervals of either Xylocaine/saline solution or Xylocaine/proliferant into the posterior sacroiliac and interspinous ligaments, fascia, and joint capsules of the low back from L4 to the sacrum. Patients were observed with a visual analog, disability, and pain grid scores, and with objective computerized triaxial tests of lumbar function for 6 months following conclusion of injections. Pretreatment imaging tests with either magnetic resonance imaging (MRI) or computed tomography (CT) scans were performed in all patients. Thirty of the 39 patients randomly assigned to the proliferant group achieved a 50% or greater diminution in pain or disability scores at 6 months compared to 21 of 40 in the group receiving lidocaine (p = 0.042). Subjective parameters measured at 6 months posttreatment improved (p < 0.001) overall in both the treatment and control group compared to baseline. Improvements in visual analog (p = 0.056), disability (p = 0.068), and pain grid scores (p = 0.025) were greater in the proliferant group. Objective testing of range of motion, isometric strength, and velocity of movement showed significant improvements in both groups following treatment but did not favor either group. The MRI and CT scans showed significant abnormalities in both groups, but these did not correlate with subjective complaints and were not predictive of response to treatment. PMID- 8439714 TI - Length dependence of a halo orthosis on cervical immobilization. AB - This study was designed to observe the length dependence of a well-molded fiberglass body cast attached to a halo on motion restriction in an unstable cadaveric cervical spine. Also, by using this technique, comparison between the immobilization provided by a body cast and that provided by a standard premolded polyethylene halo vest could be made. Extreme cervical instability was created on adult cadavers. A halo ring was applied and then attached to a fiberglass body cast or to a polyethylene halo vest. Sequential lateral cervical radiographs were obtained during maximum flexion as the body cast was shortened from the level of the iliac crests to the level of the xiphoid process. Radiographic motion was also assessed within the polyethylene halo vest. Results revealed minimal motion difference as the fiberglass body cast was sequentially shortened. In contrast, motions within the polyethylene halo vest were variable. These results suggest that cervical immobilization may be relatively independent of support structure length and that immobilization can be maintained by a well-fitting halo vest extending to the level of the xiphoid process. PMID- 8439715 TI - The effect of long-term high-dose naloxone infusion in experimental blunt spinal cord injury. AB - The effect of long-term continuous subcutaneous infusion of naloxone on blunt spinal cord injury in the rat was assessed using four tests of neurological function, seven histological categories, and two electrophysiological measures. All four neurological function tests showed a trend toward improvement in naloxone-treated animals: the degree of improvement was statistically significant in two of the four categories. A significant reduction in myelin sheath edema was found in the naloxone-treated animals. Although there was a decrease in corticomotor-evoked potentials complexity following injury, there was no significant difference in naloxone-treated animals. Somatosensory-evoked potentials were significantly increased in amplitude and latency in naloxone treated animals. This increase was most apparent at 60 min: no difference was found by 3 weeks postinjury. These results confirm earlier reports that naloxone can ameliorate the functional neurological deficits of spinal cord injury. Naloxone also produces alterations in the somatosensory-evoked responses in the early phase of treatment and significantly reduces myelin sheath edema. PMID- 8439716 TI - Computer-assisted DREZ microcoagulation: posttraumatic spinal deafferentation pain. AB - Our data demonstrate that approximately 23-29% of standard dorsal root entry zone (DREZ) microcoagulation procedures fail to relieve pain due to inadequate thermal lesions and that approximately 39% fail due to insufficient superior extent of lesions. The remaining failures are related to inadequate lesion placement, improper selection of patients, and, rarely, posttraumatic spinal deafferentation pain resulting from other non-DREZ mechanisms. Computer-assisted DREZ microcoagulation is a satisfactory procedure to treat intractable posttraumatic spinal deafferentation pain, brachial plexus avulsion pain, and lumbosacral nerve root avulsion pain. In all these conditions we have identified areas of abnormal focal hyperactivity in the DREZ area. Perhaps this procedure can be applied to other central pain conditions if, using this technique, abnormal focal hyperactivity is demonstrated to be present. PMID- 8439717 TI - Anatomical and roentgenographic features of atlantooccipital instability. AB - An anatomical study using six fresh, human cadaveric cervical spine specimens was performed. After the dissection of all soft tissue, flexion-extension radiographs were obtained to verify initial stability. A sagittal plane bone cut was then made, centered on the odontoid and sparing the alar ligaments, the tectorial membrane, and the atlantooccipital (AO) ligaments. Repeat flexion-extension radiographs and photographs were taken to document maintenance of stability of these hemisections. The occipital-atlantoaxial ligaments were then individually and sequentially incised, maintaining all other structures each time. After the sectioning of each ligament, flexion-extension radiographs and photographs were obtained to identify subsequent motion patterns. Both gross anatomical and roentgenographic examinations demonstrated the important stabilizing role of the tectorial membrane in flexion. Additionally, contact between the posterior arch of C1 and the occiput limited hyperextension as a secondary restraint once the tectorial membrane was sectioned. Furthermore, the AO ligaments proved to play an insignificant role in the preservation of AO stability through a flexion extension arc of motion. Under normal circumstances, the AO articulation is not excessively stressed. However, acute AO injury, as well as the insidious failure of these ligaments, has been documented in several cases involving various pathologies. This study demonstrates a mechanism of instability and highlights the essential role of the tectorial membrane in maintaining upper cervical spine stability. PMID- 8439718 TI - Modifications to the transverse Caspar cervical retractor blades optimized for a single-level anterior cervical discectomy. AB - A modification of the transverse Caspar cervical soft-tissue retractor blades for their use in a single-level anterior cervical discectomy is presented. These modified retractor blades are similarly inserted into the elevated anterior mesial portion of the longus colli muscles. However, they allow a smaller skin incision, less soft-tissue dissection, and do not require use of the superior and inferior smooth retractor blades, while providing the same surgical vision and operative ability in the disc space as does the four-bladed Caspar retractor system. PMID- 8439719 TI - Cervical spine injury in an air-bag-equipped vehicle. AB - We describe a patient who suffered an upper cervical spine fracture despite wearing a seat belt and deployment of an air bag system. All individuals treating trauma victims should be aware that a potentially life-threatening injury can occur despite proper use of optimal available restraints. PMID- 8439720 TI - Spinal subdural hematoma: a rare cause of recurrent postoperative radiculopathy. AB - Spinal subdural hematoma is a rare condition with numerous etiologies. It is even more rare in the postoperative period and must be differentiated from the more common causes of postoperative pain and radiculopathy. We report a 36-year-old man presenting 6 weeks after surgery with incapacitating pain who was found to have a subdural but extraarachnoid fluid collection. We describe clinical presentation, radiological findings, etiology, and treatment. We conclude that, although rare, the spinal subdural hematoma should be considered in patients with postoperative pain. Prompt recognition and surgical evacuation are important for optimal recovery. PMID- 8439721 TI - Digital subtraction lumbar diskography: technical note. AB - A simple technique is described for increasing the conspicuousness of radiographic contrast media injection during lumbar diskography. Injections are monitored with a digital C-arm unit using digital subtraction technique, rather than conventional fluoroscopic technique. Fourteen disk levels in six patients have so far been imaged with digital subtraction lumbar diskography. The technique permits more precise monitoring of contrast injections, and may be particularly useful for detecting minute test injections in spaces other than the nucleus pulposus, as well as for diskography on large and overweight patients. PMID- 8439722 TI - Hyndman-Schneider procedure for paraplegia caused by a sharp, angular scoliosis: a case report and a review of the literature. AB - Scoliosis causing neurologic deficit is rare. Nonoperative treatment has been shown to be unsuccessful in reversing the condition or preventing further neurologic progression. Surgical intervention using the Hyndman-Schneider approach (costotransversectomy and apical pedicle resection) decompresses the spinal cord by transposing it into the concavity of the deformity. Although it is a demanding procedure with significant risks, lateral spinal cord transposition is the preferable procedure to provide full neurologic recovery in successful cases. PMID- 8439723 TI - Latissimus dorsi rupture: an unusual complication of anterior spine surgery. AB - Anterior spinal surgery is a common part of the treatment for spinal trauma and deformity. Two cases of an unusual postoperative complication of the surgical exposure for anterior spinal fusion with rib strut grafts are herein reviewed. In each case, the patient presented 3-6 months postoperatively with a large, painful mass along the posterior axillary line near the surgical incision. The mass was diagnosed as a rupture of the latissimus dorsi. The cause of this disruption is unclear, but it appears to be a complication of the surgical approach; therefore, surgeons performing transthoracic and thoracoabdominal approaches should be aware of it. PMID- 8439724 TI - Right-sided cervical radiculopathy. PMID- 8439725 TI - Tuberculosis of the spine. PMID- 8439726 TI - Incorporation of copy-number control elements into yeast artificial chromosomes by targeted homologous recombination. AB - We have developed a pair of vectors for exchanging yeast artificial chromosome (YAC) arms by targeted homologous recombination. These conversion vectors allow the introduction of copy-number control elements into YACs constructed with pYAC4 or related vectors. YACs modified in this way provide an enriched source of DNA for genetic or biochemical studies. A LYS2 gene on the conversion vector provides a genetic selection for the modified YACs after transformation with appropriately prepared vector. A background of Lys+ clones that do not contain modified YACs is also present. However, clones with converted YACs can be distinguished from this background by counter-screening for loss of the original p YAC4 TRP1 arm (Trp- phenotype). The elimination of yeast replication origins (ARS elements) from the conversion vectors increased the frequency of Lys+ Trp- clones, but resulted in weaker amplification. Several YACs have been converted with these vectors, and the fate of the transformed DNA and of the resident YAC DNA has been systematically investigated. PMID- 8439727 TI - Definition, distribution, and use of a conserved Bovidae retroposon element sequence motif. AB - Based on a data-base search, the sequences of 32 Bovidae retroposon elements have been compared. Two conserved areas are identified, and one of the corresponding sequences of the derived bovine consensus was used to design oligonucleotides as primer molecules for random DNA amplification of Bovidae DNA. Such a primer binding site should occur on average every 10,000 bp in the bovine genome, as suggested by a survey of published sequences. This estimate about the distribution of these possible primer binding sites was experimentally substantiated by mapping four of these primer binding sites within 40 kb of contiguous bovine DNA, carrying the heretofore undescribed bovine lactoferrin gene. Furthermore, these conserved, ubiquitous sequence motifs prove to be useful for mapping of bovine DNA. PMID- 8439728 TI - Multiplication of Mhc-DRB5 loci in the orangutan: implications for the evolution of DRB haplotypes. AB - The beta chain-encoding (B) class II genes of the primate major histocompatibility complex belong to several families. The DRB family of class II genes is distinguished by the occurrence of haplotype polymorphism--the existence of multiple chromosomal forms differing in length, gene number, and gene combinations, each form occurring at an appreciable frequency in the population. Some of the haplotypes, or fragments thereof, are shared by humans, chimpanzees, and gorillas. In an effort to follow the DRB haplotype polymorphism further back in time, we constructed DRB contig maps of the two chromosomes present in the orangutan cell line CP81. Two types of genes were found in the two haplotypes, Popy-DRB5 and Popy-DRB1*03, the former occurring in two copies and one gene fragment in each haplotype, so that the CP81 cell line contains four complete DRB5 genes and two DRB5 fragments altogether. Since the four genes are more closely related to one another than they are to other DRB5 genes, they must have arisen from a single ancestral copy by multiple duplications. At the same time, however, the two CP81 haplotypes differ considerably in their restriction enzyme sites and in the presence of Alu elements at different positions, indicating that they have been separated for a length of time that exceeds the lifespan of a primate species. Moreover, a segment of about 100 kilobase pairs is shared between the orangutan CP81-1 and the human HLA-DR2 haplotype. These findings indicate that part of the haplotype polymorphism may have persisted for more than 13 million years, which is the estimated time of human-orangutan divergence. PMID- 8439729 TI - Genetic mapping of the X-linked dominant mutations striated (Str) and bare patches (Bpa) to a 600-kb region of the mouse X chromosome: implications for mapping human disorders in Xq28. AB - Striated (Str) and bare patches (Bpa) are X-irradiation-induced, X-linked dominant mouse mutations that are lethal prenatally in hemizygous males. To map the Str mutation, we generated a backcross involving Mus castaneus. Pedigree analysis of 193 affected female and normal male progeny from the cross places Str extremely close to DXMIT1 and favors a gene order of (Cf-9)-Ids-Gabra3-DXS1104h (Str, DXMIT1)-F8a-DXPas8-DXBay6-DXMIT6 for the loci studied. This region of the mouse X Chromosome (Chr) is syntenic with proximal human Xq28. Based on the mode of inheritance and clinical phenotype, Str may be a homolog of human familial incontinentia pigmenti (IP2). Further refinement of our genetic mapping of bare patches positions that locus between DXS1104h and DXPas8 in the same region as Str, raising the possibility that Bpa and Str may be allelic or are due to mutations in overlapping contiguous genes. PMID- 8439730 TI - Genetic mapping of opioid binding protein gene(s) to mouse chromosome 9. PMID- 8439731 TI - Localization of the tryptophanyl tRNA synthetase gene (WARS) on human and bovine chromosomes by in situ hybridization. PMID- 8439732 TI - The functional genes for protein synthesis initiation factor 4AI and 4AII map to mouse chromosomes 11 and 16. PMID- 8439733 TI - An improved low racemization solid-phase method for the synthesis of reduced dipeptide (psi CH2NH) bond isosteres. AB - Preparation of peptides containing a reduced bond isostere reveals that the solid phase procedure introduced by D.H. Coy is prone to generate significant levels of peptide diastereomers. A systematic study was conducted analyzing reaction conditions and reagents for causes of this epimerization. These studies show that trapping of the intermediate imine is the major contributor to generation of peptide diastereomers in the final product. These studies also suggest that careful adjustments of solvent and pH are necessary to suppress epimerization. Thus, an improved solid-phase procedure has been devised that efficiently traps the intermediate imine, resulting in extremely low levels of peptide diastereomers. These improved procedures have been successfully used in synthesis from 0.25 mmol to > 50 mmol batch sizes. PMID- 8439734 TI - Direct quantitative determination of peptides and proteins in PVDF transfer membrane using a computing densitometer. AB - In this paper we describe a method that makes it possible to quantify bands or spots directly on membranes using a computing densitometer. The method is based on the fact that polyvinylidene difluoride (PVDF) membrane is translucent when immersed in solutions containing > 50% methanol. Peptide markers (2.512-16.949 kDa), as well as purified Neuropeptide Y, have been used to optimize direct densitometry of PVDF membrane. For all peptides and proteins analyzed, the optical response of the instrument to peptide and protein bands in PVDF membrane wetted in 50% methanol was linear and highly reproducible. The method described here is useful for a rapid quantification of peptides and proteins on PVDF membrane and is an alternative to RIA, ELISA or bioassay. PMID- 8439735 TI - Edman degradation sequence analysis of resin-bound peptides synthesized by 9 fluorenylmethoxycarbonyl chemistry. AB - The efficacy of Edman degradation sequence analysis for evaluating the synthetic efficiency of peptide-resin assembly by 9-fluorenylmethoxycarbonyl (Fmoc) solid phase methodology has been studied. Prior researchers have described the use of solid-phase "preview" sequence analysis for peptides synthesized by tertiary butyloxycarbonyl (Boc) chemistry, where benzyl-based side-chain protecting groups and peptide-resin linkers are stable to the conditions of Edman chemistry. We have successfully sequenced a variety of resin-bound peptides synthesized by Fmoc chemistry, where tertiary-butyl-based side-chain protecting groups and peptide resin linkers are labile to the conditions of Edman chemistry. Crude peptides are liberated from trifluoroacetic acid-labile linkers during the first cycle of Edman degradation and subsequently "embedded" in membranes. For peptides up to 20 residues, embedded sequencing repetitive yields were comparable to those of solid phase sequencing. Preview sequencing of resin-bound Fmoc-synthesized peptides proved to be advantageous compared to other analytical methods, in that synthetic failures were detected and quantitated at the point of occurrence, regardless of whether incomplete Fmoc deprotection or incomplete coupling was responsible, and without interference from by-products formed during peptide-resin cleavage. Quantitative ninhydrin analysis, which previously has been found to give false positive results due to removal of the Fmoc group by a combination of reagents and high temperature, gave false negative results in this study, most probably due to incomplete removal of the Fmoc group prior to coupling. Quantitative sequence analysis results were supported by high-performance liquid chromatographic, amino acid and electrospray mass spectrometric analyses of the crude and purified peptides. PMID- 8439736 TI - An evaluation of microwave heating for the rapid hydrolysis of peptide samples for chiral amino acid analysis. AB - The hydrolysis of peptide samples in 6 N deuterium chloride by microwave heating has been investigated. The influence of the power and time of heating on the recovery of the amino acids and on their racemization was studied. A high recovery of sensitive amino acids and minimal racemization, as determined by the amount of deuterium incorporation, is obtained by using an intermediate irradiation power and 30 min reaction time. PMID- 8439737 TI - Practical multipeptide synthesis: dedicated software for the definition of multiple, overlapping peptides covering polypeptide sequences. AB - A personal computer program for the conversion of linear amino acid sequences to multiple, small, overlapping peptide sequences has been developed. Peptide lengths and "jumps" (the distance between two consecutive overlapping peptides) are defined by the user. To facilitate the use of the program for parallel solid phase chemical peptide syntheses for the synchronous production of multiple peptides, amino acids at each acylation step are laid out by the program in a convenient standard multi-well setup. Also, the total number of equivalents, as well as the derived amount in milligrams (depend-ending on user-defined equivalent weights and molar surplus), of each amino acid are given. The program facilitates the implementation of multipeptide synthesis, e.g., for the elucidation of polypeptide structure-function relationships, and greatly reduces the risk of introducing mistakes at the planning step. It is written in Pascal and runs on any DOS-based personal computer. No special graphic display is needed. PMID- 8439738 TI - Evidence for visual cortical area homologs in cat and macaque monkey. AB - The maps of visuotopically discrete visual cerebral cortical areas in the cat and the macaque monkey are compared and gaps in knowledge are identified that limit such comparisons. Cat areas 17, 18, and 19 can be equated with macaque areas V1, V2, and V3, respectively, based on criteria of relative position in the cortical mantle, internal organization of visual field representations, and trans- and subcortical connections. Using these same criteria, a visual area on the medial bank of the lateral suprasylvian sulcus (area PMLS) in the cat can be equated with macaque area V5. The equivalences are supported by data on neuronal receptive field properties and the contributions the areas make to visual behavior. Although the data are scanty for most other visual areas, there are enough data tentatively to equate collectively cat areas 20a and 20b with macaque areas TF and TH and to liken cat areas 21a and 21b with macaque area V4. What is not clear is if there is a region in cat that is equivalent to area TE in the macaque monkey. If there is, it likely lies on the banks of the posterior suprasylvian sulcus between areas 20 and 21 and the polysensory cortex of the posterior ectosylvian gyrus. Knowledge gained from prior research on macaque areas V4 and TE can be used to formulate specific additional investigations of cat area 21 and the uncharted posterior suprasylvian sulcus. In addition, prior investigations carried out on cat area 20 can be used to devise specific explorations of macaque areas TF and TH. PMID- 8439739 TI - Regenerative activity in apical dendrites of pyramidal cells in neocortex. AB - In intracellular recordings from three neocortical pyramidal cells in vitro, intracellular dye injection identified the impalement site as the primary trunk of the apical dendrite. Dendritic recordings displayed two types of regenerative events: relatively fast, low-threshold spikes with amplitudes of 12-69 mV, and slower, higher-threshold spikes up to 80 mV in amplitude. This distinctive dendritic firing pattern was also encountered in six recordings without dye filled electrodes. Fast spike frequency was extremely sensitive to small changes in membrane potential at the recording site. In one recording, the fast spikes were blocked by 1 microM TTX, while slow events were spared. A computational model of a pyramidal cell was constructed to assist in interpreting the recordings. Simulations suggested that the fast spikes were generated primarily by active Na+ conductance concentrated at a distance from the impalement site, probably in the region of the soma. The low threshold of the fast spikes suggested that Na+ channels also exist in the apical dendrites, where they have a relatively low density. The data strongly imply that there are Ca2+ channels in the apical dendrites. PMID- 8439740 TI - Numerical relationships between geniculocortical afferents and pyramidal cell modules in cat primary visual cortex. AB - An analysis has been made of the quantitative data available on the number of pyramidal cell modules of layer IV neurons, and of geniculocortical axons and their synapses in cat striate cortex. It is found that the convergence of geniculocortical afferents upon any one pyramidal cell module is enormous, since in any one location there is overlap between 360-540 X-axons and 300-540 Y-axons. In total, the X- and Y-axonal arbors provide some 1640 x 10(6) synapses to area 17, which is equivalent to a ratio of 160-200 synapses per layer IV neuron. These values assume that geniculocortical terminals synapse only with the spiny stellate cells of layer IV. The values are reduced to 100-125 per spiny stellate cell when account is taken of the synapses that involve the dendrites that enter layer IV from neurons with cell bodies in other layers. Since each layer IV neuron receives some 2500 asymmetric synapses, this means that only 5% of the total excitatory input to a layer IV neuron seems to be provided by the geniculocortical afferents. Further, if the boutons in the geniculocortical axonal arbors are distributed homogeneously across layer IV, each axon could only provide one synapse to about one in four of the layer IV neurons encompassed by its plexus. It may be, however, that instead of being spread evenly, boutons in individual arbors converge upon individual neurons to supply a number of synapses to them. But even so, it seems unlikely that any individual geniculate axon could dominate the activity of a particular cortical neuron. PMID- 8439741 TI - CA-1, a novel phosphoprotein, interacts with the promoter of the cab140 gene in Arabidopsis and is undetectable in det1 mutant seedlings. AB - We have identified and partially purified a DNA binding protein from Arabidopsis that interacts specifically with the phytochrome-responsive promoter of the Arabidopsis cab140 gene. Promoter deletion analyses in transgenic tobacco showed that, if a region that includes the sequence interacting with this protein was deleted, both expression and phytochrome responsiveness were lost. The protein protected a cytosine- and adenine-rich region from DNase I digestion, and therefore it has been called Ca-1. CA-1 was shown to be a phosphoprotein, and dephosphorylation changed the migration of the protein-DNA complex in DNA mobility shift assays. The data suggested that the protein has an apparent molecular weight of 70,000. The CA-1-protected region of the cab140 promoter included an ACGT motif that has been found in the target sequences of a number of bZIP transcription factors, but the binding behavior of CA-1 differed from those factors. CA-1 binding activity was present in plants grown in either white light or darkness, and no differences in the binding activity were detected in the dark grown plants after short red or white light treatments. However, the CA-1 binding activity was not detectable in extracts of seedlings bearing the det1 mutation grown in the dark and given the same illumination treatments as wild type. In contrast to wild type, the mutant seedlings express cab RNA at a high level when grown in complete darkness, and we found no further increase in cab140 mRNA in response to brief red illumination. The lack of CA-1 activity in the det1 mutant suggests that it may function as a transcriptional repressor regulating the expression of the cab140 gene in Arabidopsis. PMID- 8439742 TI - Conservation of the b mating-type gene complex among bipolar and tetrapolar smut fungi. AB - In the phytopathogenic fungus Ustilago hordei, one locus with two alternate alleles, MAT-1 and MAT-2, controls mating and the establishment of the infectious dikaryon (bipolar mating). In contrast, for U. maydis, these functions are associated with two different gene complexes, called a and b (tetrapolar mating); the a complex has two alternate specificities, and the b gene complex is multiallelic. We have found homologs for the b gene complex in U. hordei and have cloned one from each mating type using sequences from one bEast allele of U. maydis as a probe. Sequence analysis revealed two divergent open reading frames in each b complex, which we called bW (bWest) and bE (bEast) in analogy with the b gene complex of U. maydis. The predicted bW and bE gene products from the two different mating types showed approximately 75% identity when homologous polypeptides were compared. All of the characterized bW and bE gene products have variable amino-terminal regions, conserved carboxy-terminal regions, and similar homeodomain motifs. Sequence comparisons with the bW1 and bE1 genes of U. maydis showed conservation in organization and structure. Transformation of the U. hordei b gene complex into a U. hordei strain of opposite mating type showed that the b genes from the two mating types are functional alleles. The U. hordei b genes, when introduced into U. maydis, rendered the haploid transformants weakly pathogenic on maize. These results indicate that structurally and functionally conserved b genes are present in U. hordei. PMID- 8439743 TI - hy8, a new class of arabidopsis long hypocotyl mutants deficient in functional phytochrome A. AB - Emerging evidence suggests that individual members of the phytochrome family of photoreceptors may regulate discrete facets of plant photomorphogenesis. We report here the isolation of phytochrome A mutants of Arabidopsis using a novel screening strategy aimed at detecting seedlings with long hypocotyls in prolonged far-red light. Complementation analysis of 10 selected mutant lines showed that each represents an independent, recessive allele at a new locus, designated hy8. Immunoblot and spectrophotometric analyses of two of these lines, hy8-1 and hy8 2, showed that, whereas phytochromes B and C are expressed at wild-type levels, phytochrome A is undetectable, thus indicating that the long hypocotyl phenotype displayed by these mutants is caused by phytochrome A deficiency. A third allele, hy8-3, expresses wild-type levels of spectrally normal phytochrome A, suggesting a mutation that has resulted in loss of biological activity in an otherwise photochemically active photoreceptor molecule. Together with physiological experiments, these data provide direct evidence that endogenous phytochrome A is responsible for the "far-red high irradiance response" of etiolated seedlings, but does not play a major role in mediating responses to prolonged red or white light. Because the hy8 and the phytochrome B-deficient hy3 mutants exhibit reciprocal responsivity toward prolonged red and far-red light, respectively, the evidence indicates that phytochromes A and B have distinct photosensory roles in regulating seedling development. PMID- 8439744 TI - Translation of the mRNA of the maize transcriptional activator Opaque-2 is inhibited by upstream open reading frames present in the leader sequence. AB - The protein encoded by the Opaque-2 (O2) gene is a transcription factor, translated from an mRNA that possesses an unusually long 5' leader sequence containing three upstream open reading frames (uORFs). The efficiency of translation of O2 mRNA has been tested in vivo by a transient assay in which the level of activation of the b32 promoter, a natural target of O2 protein, is measured. We show that uORF-less O2 alleles possess a higher transactivation value than the wild-type allele and that the reduction in transactivation due to the uORFs is a cis-dominant effect. The data presented indicate that both uORF1 and uORF2 are involved in the reducing effect and suggest that both are likely to be translated. PMID- 8439745 TI - Expression of a self-incompatibility gene in a self-compatible line of Brassica oleracea. AB - In cruciferous plants, self-pollination is prevented by the action of genes situated at the self-incompatibility locus or S-locus. The self-incompatibility reaction is associated with expression of stigma glycoproteins encoded by the S locus glycoprotein (SLG) gene. Only a few cases of self-compatible plants derived from self-incompatible lines in the crucifer Brassica have been reported. In these cases, self-compatibility was generally ascribed to the action of single genes unlinked to the S-locus. In contrast, we report here a line of Brassica oleracea var acephala with a self-compatible phenotype linked to the S-locus. By means of both biochemical and immunochemical analyses, we showed that this self compatible (Sc) line nonetheless possesses stigmatic SLGs (SLG-Sc) that are expressed with a similar spatial and temporal pattern to that described for the SLGs of self-incompatible Brassica plants. Moreover, the SLG-Sc products segregate with the self-compatibility phenotype in F2 progeny, suggesting that changes at the S-locus may be responsible for the occurrence of the self compatibility character. A cDNA clone encoding the SLG-Sc product was isolated, and the deduced amino acid sequence showed this glycoprotein to be highly homologous to the pollen recessive S2 allele glycoprotein. Hence, self compatibility in this Brassica Sc line correlates with the expression of a pollen recessive-like S allele in the stigma. PMID- 8439746 TI - MsERK1: a mitogen-activated protein kinase from a flowering plant. AB - The induction of proliferation and differentiation in cultured mammalian cells is mediated by a cascade of protein phosphorylations. A key enzyme in this signaling pathway is mitogen-activated protein (MAP) kinase (or ERK, extracellular signal regulated kinase). We report the recovery of a full-length cDNA clone encoding a MAP kinase from alfalfa. We have named the 44-kD protein encoded by this clone MsERK1. Recombinant MsERK1 (rMsERK1), when overexpressed in Escherichia coli, is recognized by antibodies raised against MAP kinases from rat, Xenopus, and sea star and by anti-phosphotyrosine antibodies. Site-directed mutagenesis of MsERK1 demonstrated that Tyr-215 is either directly or indirectly responsible for recognition of the protein by anti-phosphotyrosine antibodies. Semipurified rMsERK1 phosphorylated itself and a model substrate, myelin basic protein, in vitro, but the Tyr-215 mutant did neither. Genomic DNA gel blot analysis suggested that the gene that encodes MsERK1 is either a member of a small multigene family or a member of a polymorphic allelic series in alfalfa. Because MAP kinase activation has been associated with mitotic stimulation in animal systems, such an enzyme may play a role in the mitogenic induction of symbiotic root nodules on alfalfa by Rhizobium signal molecules. PMID- 8439748 TI - Spread of disease via the subperitoneal space: the small bowel mesentery. AB - The designation of the subperitoneal space emphasizes the continuum of the potential space of extraperitoneal and intraperitoneal areolar tissue traversed by blood vessels, lymphatics, and nerves. Across its root, the subserous connective tissue of the small bowel mesentery is anatomically continuous with that deep to the posterior parietal peritoneum. There is thereby provided an avenue of spread from multiple sites to and from the small bowel mesentery and its relationships. These include perforated lesions of the bowel, pancreatitis, lymphoma, neuroblastoma, leiomyosarcoma of small bowel, and hemorrhage of retroperitoneal and pelvic origin. PMID- 8439747 TI - Structure and function of plant cell wall proteins. PMID- 8439749 TI - Bidirectional spread of disease via the subperitoneal space: the lower abdomen and left pelvis. AB - In early fetal life a persistent interconnection between the peritoneum and retroperitoneum of the abdomen and pelvis is formed--the subperitoneal space (SS). This paper serves to complete the description of the specific anatomical nuances of the SS as they relate to the bidirectional direct spread of disease in the left lower abdomen and pelvis. Described are the two avenues of communication (central and lateral pathways) within this portion of the SS. Selected cases illustrating the bidirectional spread of disease processes within this portion of the SS are reported. PMID- 8439750 TI - MRI demonstration of peritoneal ligaments and mesenteries. AB - The normal appearances of 14 peritoneal ligaments and mesenteries were demonstrated by magnetic resonance imaging (MRI). Antegrade or retrograde air introduction was employed to distend and mark the gastrointestinal tract. Delineation of these ligaments and mesenteries was helped by the presence of ascites and air-distended bowel loops. The different intraperitoneal compartments are also demonstrated. PMID- 8439751 TI - The use of MRI in bowel obstruction. AB - Nine patients with clinical or radiographic evidences of bowel obstruction were examined by magnetic resonance imaging. Retrograde insufflation of 1000-1200 ml of air through a Foley catheter placed in the rectum was employed. Scopolamine was used to inhibit bowel peristalsis and possibly relax the ileocecal valve. The administered air successfully distended the colon and the small bowel distal to the obstruction in seven of the nine cases. The air-filled small bowel loops were useful in delineating the obstruction sites and adjacent lesions in these seven cases. The diagnosis was established by means of surgery in six cases and by clinical course in three cases. The causes of obstruction included four peritoneal carcinomatoses, and one each of supravesical hernia, intussusception, adhesive band, benign granulomatous stricture, and radiational stricture. The site of obstruction was the distal small bowel in eight cases, and the rectosigmoid colon in one case. PMID- 8439752 TI - Intra-anal intussusception: diagnosis by posteroanterior stress proctography. AB - Intra-anal intussusception was diagnosed in eight of 39 patients on evacuation proctography. Posteroanterior views revealed prolapse of the infolded rectum into the anal canal on staining in seven of eight patients, associated with splaying open of the anal canal and sudden distal movement of the fold during prolapse. Similar changes were seen in four of 31 patients in whom intussusception had not been diagnosed on lateral evacuation proctography. The pattern of the collapsed rectum was assessed for fold length, thickness, and angulation in relation to the midline of the rectum. Infoldings that prolapsed were closer to the anorectal junction on stress (mean 14.6: 42.4 mm, p < 0.0001) showed greater change in height between rest and strain (28.8: 14.6 mm, p < 0.05) and became more acutely angled during straining (41.9: 5.3 degrees, p < 0.01). Intra-anal intussusception may be missed in 33% (four of 12 patients) on routine evacuation proctography. Posteroanterior stress proctography is a simple supplementary examination to validate intussusception. PMID- 8439753 TI - Agenesis and pseudo-agenesis of the dorsal pancreas. AB - Agenesis of the dorsal pancreatic anlage is a very unusual congenital anomaly. The case reported appears to be accompanied by hypertrophy of the ventral gland. Atrophy of the pancreas following an episode of acute pancreatitis is also very unusual. When the atrophy spares the uncinate process, it may also resemble agenesis of the dorsal gland. PMID- 8439754 TI - Anatomical variation of pancreatobiliary ducts in biliary stone diseases. AB - Endoscopic retrograde cholangiopancreatography examinations were prospectively analyzed to determine whether anatomical variations of ductal systems have a role in the pathogenesis of cholecystolithiasis and choledocholithiasis. Included were 140 normal examinations (control group), 102 patients with cholecystolithiasis, and 68 patients with choledocholithiasis (primary stones in the common bile duct). Low entry of the cystic duct was observed frequently in patients with cholecystolithiasis (15.7% vs. 2.1% in control, p < 0.01). No preferential type of course of the cystic duct was observed in patients with cholecystolithiasis and choledocholithiasis. Separate openings of the bile and pancreatic ducts were significantly prevalent in patients with choledocholithiasis (53.5% vs. 30.6% in control, p < 0.01). Common channel was significantly short in patients with cholecystolithiasis. Incidence of juxtapapillary duodenal diverticula was significant in patients with choledocholithiasis. These observations suggest that some of the pancreatobiliary ductal anatomy may be closely implicated in the development of gallstone diseases. PMID- 8439755 TI - Imaging of complications of laparoscopic cholecystectomy. AB - Laparoscopic cholecystectomy has gained widespread acceptance for treatment of cholelithiasis. Because radiologists have a primary role in recognizing and treating complications of this surgical technique, we reviewed the clinical records and imaging studies of 29 patients with complications after laparoscopic cholecystectomy. Complications included bile duct injuries (15 cases), retained common bile duct stones (seven cases), cystic duct stump leak (four cases), bowel perforation (two cases), abdominal abscess (two cases), intraperitoneal gallstones (2), and failure to diagnose malignant bile duct obstruction (one case). Twenty-two patients required reoperation, and one patient with bowel perforation died. Eleven of 15 bile duct injuries were imaged prior to hepaticojejunostomy. Nine of 11 were proximal bile duct injuries within 2 cm of the junction of the right and left bile ducts. Endoscopic retrograde cholangiography (ERC) identified the distal extent of injuries, but transhepatic cholangiography (THC) was necessary to fully evaluate the proximal extent of the bile duct abnormalities. ERC was used for diagnosis and treatment of the seven patients with choledocholithiasis. Abdominal films showed intraperitoneal in one patient with bowel perforation, intraperitoneal stones in a second patient, and intraabdominal abscess in one of two patients in whom abdominal films were performed. Computed tomography (CT), done in three patients with bowel perforation or abscess, showed the one duodenal perforation, and the two abscesses. CT also showed bilomas, intraperitoneal gallstones, and unsuspected malignancy. Imaging studies detected and defined complications after laparoscopic cholecystectomy in all cases. PMID- 8439756 TI - Intrahepatic splenosis mimicking a liver tumor. AB - A rare case of ectopic splenic tissue in the liver is presented which mimicked a liver tumor. It is considered that some splenic tissue was seeded in the liver during the splenectomy that the patient underwent 23 years ago. Computed tomography (CT), magnetic resonance imaging (MRI), and angiographic features of this lesion were almost indistinguishable from those of other liver tumors. PMID- 8439757 TI - Hepatic and splenic sarcoidosis: ultrasound and MR imaging. AB - Abdominal imaging studies may be performed for various indications in patients known to have sarcoidosis. To assess magnetic resonance imaging (MRI) and sonographic ability to detect abnormalities in sarcoidosis patients with abdominal involvement, a prospective study on 18 selected patients was performed. Besides organomegaly, when present, ultrasound demonstrated normal or increased hepatic parenchymal echogenicity, coarsening of the liver parenchyma with or without discrete nodules, focal calcifications, as well as contour irregularity. Splenic discrete nodules were seen on ultrasound in a single patient. Besides organomegaly, MRI abnormalities include abnormal hepatic signal intensity, discrete nodules, contour irregularity, speculation of small hepatic vascular branches, and a high periportal signal intensity. MRI splenic abnormalities include contour irregularity, nodularity, and abnormal signal intensity. The data presented in this study reveals the spectrum of ultrasound and MRI findings in sarcoidosis patients with abdominal organ involvement, potentially enabling the evaluation of the severity of the disease. MRI appears more sensitive than ultrasound for study of abdominal sarcoidosis. PMID- 8439758 TI - MR imaging in intracystic hemorrhage of simple hepatic cysts. AB - Intracystic hemorrhage of simple hepatic cysts is one of the most frequent complications. Ultrasonography (US) and computed tomography (CT) may show abnormal findings and mimic other diseases. We describe magnetic resonance (MR) imaging in four patients with intracystic hemorrhage confirmed by surgery or percutaneous aspiration. In all cases the lesions were hyperintense on both T1- and T2-weighted sequences. In three of the four cases the signal was heterogeneous on T1-weighted sequences. Two cases of a thickened wall and one case of a fluid-fluid level were also observed. We suggest that MR imaging may be helpful to differentiate intracystic hemorrhage from other cystic lesions by showing high signal on T1- and T2-weighted sequences. PMID- 8439759 TI - Hepatic mesenchymal sarcoma: MRI findings. AB - Hepatic undifferentiated mesenchymal sarcoma is a rare pediatric malignant neoplasm. We present three children, aged 7, 8, and 12 years, with this tumor. Clinical presentation was abdominal pain, palpable mass, asthenia, anorexia, and weight loss. One had jaundice. All three lesions were detected on ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI). MRI localized the lesions more accurately than the other methods, with good resectability correlation. On MRI, these tumors were markedly hyperintense on long TR/TE spin-echo (SE) and short-time inversion recovery (STIR) sequences. This was due to the cystic areas with myxoid material and necrosis. The internal separations were hypointense on these sequences. On short TR/TE SE sequences the lesions presented a fibrous pseudocapsule (two cases), and internal hyperintense areas representing hemorrhage (two cases). MRI also detected vascular invasion (one case), biliary obstruction (one case), and hilar adenopathies (one case). The combination of hemorrhage (hyperintense on short TR/TE SE) and cystic or myxoid components (markedly hyperintense on long TR/TE SE and STIR sequences) is common in this tumor. PMID- 8439760 TI - Renal streak artifact during contrast-enhanced CT: comparison of low versus high osmolality contrast media. AB - Two hundred abdominal computed tomographic (CT) scans in 200 patients, 100 performed with low osmolality contrast (ioversol 68%, 100 ml) and 100 performed with high osmolality contrast (diatrizoate meglumine 60%, 150 ml), were retrospectively evaluated for the presence of renal streak artifact. Contrast was administered by hand injection at a rate of approximately 1-2 ml/s and sequential scanning was employed. Of the scans performed with high osmolality contrast, 70% had no artifact, 28% had minimal artifact, and only 2% had marked artifact. Only 26% of the exams performed with low osmolality contrast were artifact-free, whereas 53% demonstrated minimal artifact and 21% demonstrated marked artifact. The likelihood of encountering renal streak artifact when using low osmolality contrast agents is almost seven times greater than when high osmolality contrast agents are used. PMID- 8439761 TI - Tuberculous stricture of the urinary tract: antegrade balloon dilation and ureteral stenting. AB - In eight patients with tuberculous strictures of the urinary tract, antegrade balloon dilation and ureteral stenting was attempted. In six patients, antegrade balloon dilation was successfully performed; however, the procedure was aborted in the remaining two patients due to the failure in passing a guidewire through the stenotic lesions. In six patients in whom balloon dilation and ureteral stenting were performed, a total of nine stenotic lesions were dilated. Those were four ureteric lesions, two lesions of ureteropelvic junctions, two lesions of ureterovesical junctions, and a lesion of calyceal infundibulum. In all six patients in whom balloon dilation and ureteral stenting was successfully accomplished, intravenous urograms obtained 9-31 months after the procedure showed improvements both in contrast media excretion and in prestenotic dilatation. Antegrade balloon dilation of the urinary tract combined with ureteral stenting was an effective technique for the management of stenoses secondary to tuberculosis of the urinary tract. PMID- 8439762 TI - Is the preliminary film necessary prior to the micturating cystourethrogram in children? AB - The aim of the study was to determine the value of the preliminary film in children undergoing a micturating cystourethrogram (MCU). The coded computer reports of 806 children undergoing MCUs in a 12-month period were retrospectively reviewed for abnormalities of the lumbar spine, hips, or for calcifications. Vesicoureteric reflux was present in 185 patients (23%). Four patients had renal calculi (0.5%), and in all cases the abnormality was evident on preceding imaging of the upper urinary tract. Spinal anomalies (other than known meningomyelocele) were present in four patients. The clinically obvious abnormalities present in these were a sacral teratoma, a sacral lipoma, scoliosis with tracheo-oesophageal fistula, and a cutaneous angioma with a sacral pit. No patients (other than those with known meningomyelocele) had dislocated hips diagnosed. If the preliminary film had not been performed in 806 patients, neither spinal anomaly, renal calculus, nor congenital dislocated hip would have been missed. The low incidence of plain film anomalies indicates that in our population a plain film is not justified routinely. PMID- 8439763 TI - Duplicated mullerian duct remnants associated with unilateral renal agenesis. AB - A case of duplicated Mullerian duct remnants associated with unilateral renal agenesis in a male patient is described. This association is not uncommon in females, but is rarely recognized in male patients. The possibility of Mullerian duct cyst or enlarged prostatic utricle should be considered in the differential diagnosis of a pelvic cyst in a male patient with unilateral renal agenesis. PMID- 8439764 TI - Serotonin binding proteins in bovine retina: binding of serotonin and catecholamines. AB - Serotonin binding proteins (SBP) are present in the soluble fraction of bovine retina homogenates. These proteins can be precipitated with 30% ammonium sulphate and their binding and physicochemical characteristics are very similar to those of SBP in bovine and rat brain. Binding of [3H]serotonin to bovine retina SBP requires Fe2+ but not Fe3+. In the presence of an optimal concentration of Fe2+ (0.1 mM), these proteins behave as a single class of non-cooperative sites for [3H]serotonin (Bmax = 242 +/- 10 pmol/mg protein, KD = 0.22 +/- 0.44 microM). Competition binding studies reveal that serotonin analogs possessing an hydroxyl group on the indole ring and catecholamine analogs possessing an intact catechol moiety are potent competitors (K1 from 0.12 to 0.3 microM). In both cases, the affinity is strongly decreased if aromatic hydroxyl groups are methoxylated. Catecholamine SBP interactions can also be demonstrated directly by binding experiments with [3H]dopamine. Binding of this catecholamine is greatly enhanced by Fe2+, to a lesser extent by Cu2+ and Mn2+, but not by Fe3+. The Fe(2+) dependent binding component is saturable (Bmax = 505 +/- 30 pmol/mg protein. KD = 0.34 +/- 0.04 microM). The SBP from bovine retina show the same physicochemical properties as SBP from bovine and rat brain: they elute immediately after the void volume on a Sephacryl S100 HR (1.6 x 140 cm) gel filtration column (reflecting aggregation) and they migrate with apparent molecular weights of respectively 43 kDa and 57 kDa on native polyacrylamide gel electrophoresis. The serotonin-storing role of SBP in serotonergic neurones has already been well documented.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8439765 TI - Changes in lactate dehydrogenase isoenzyme pattern in patients with tumors of the central nervous system. AB - Lactate dehydrogenase (LDH) isoenzymes were studied in biopsy samples obtained from 100 benign and malignant brain tumors. Diagnosis was confirmed by histopathology. It is observed that all tumors investigated had elevated LDH activity and showed a LDH isoenzyme pattern which is different from that of normal brain. A pronounced cathodal shift was seen in malignant tumors like medulloblastoma, grade 3-4 astrocytomas and neuroblastomas, whereas anodal pattern was seen in benign tumors like grade 1-2 astrocytomas and oligodendrogliomas. Some tumors like meningiomas showed a midzone pattern like increased LDH3. It was possible to differentiate certain tumors on the basis of LDH isoenzyme pattern like medulloblastomas into differentiated and undifferentiated; craniopharyngiomas into recurring and non-recurring ones. LDH1/LDH5 ratio was low (< 1.0) in malignant tumors and high (5.0-14.0) in benign tumors and it was useful in differentiating tumors according to the degree of malignancy and biological behavior. It is observed that both LDH isoenzyme pattern and LDH1/LDH5 ratio could be used as an adjuvant to histopathological grading of brain tumors. PMID- 8439766 TI - Cerebellar soluble lectin and its glycoprotein ligands in the developing brain of control and dysmyelinating mutant mice. AB - The levels of an endogenous lectin, the cerebellar soluble lectin (CSL) and of its endogenous glycoprotein ligands were studied using immunoblotting and affinoblotting techniques in the forebrain of quaking, shiverer and jimpy dysmyelinating mutant mice and their respective control littermates during the postnatal development. In the controls of the mutant mice, the level of CSL showed an important increase between days 5-18 then a stabilization, although at all ages the level of CSL was reduced (at least 15%) in the control littermate of the shiverer mutant. In the shiverer mutant the developmental pattern is similar to the control but was reduced by 50% as compared to the control. In the jimpy mutant an erratic development of CSL was observed which was with quasi absence of CSL at days 12 and 25. Variation of CSL levels in the quaking brain were also observed. CSL glycoprotein ligands also showed variable developmental profiles with a special persistence with ageing of CSL-binding glycoproteins in the quaking and jimpy mice. Developmental variations were also observed between the different control littermates. These results are discussed in view of developmental roles attributed to CSL and its glycoproteins ligands in cell adhesion mechanism during brain ontogenesis and especially myelination. PMID- 8439767 TI - Effects of lysophospholipids and diacylglycerols on the transfer of arachidonic acid to phospholipids and triacylglycerols in rat brain membranes. AB - Brain membranes catalyze the acylation of lysophospholipids and diacylglycerols (DAG) to form the respective phospholipids and triacylglycerols (TAG). These acylation reactions were examined using brain plasma membrane-enriched fractions by measuring the incorporation of [14C]arachidonic acid into TAG and individual phospholipids under a variety of conditions. In the absence of added lipid substrates, the amount of [14C]arachidonic acid incorporated into TAG in the presence of ATP, Mg2+, and CoA was approx twice the amount incorporated into phosphatidylositol (PtdIns), and more than 10 times the amount incorporated into phosphatidylcholine (PtdCho), phosphatidylethanolamine (PtdEtn) and phosphatidylserine (PtdSer). These results suggest the presence of endogenous DAG, lysoPtdIns, and the required enzymes in the membrane preparations for acylation reactions. The addition of DAG, lysoPtdCho or lysoPtdIns to the incubation system resulted in a 2-20-fold increase in the rate of incorporation of labeled arachidonic acid into TAG, PtdCho or PtdIns, respectively. LysoPtdEtn and lysoPtdSer were poor substrates for the synthesis of PtdEtn and PtdSer. On the other hand, the addition of lysoPtdSer stimulated the incorporation of [14C]arachidonic acid into TAG and into most phospholipids, especially phosphatidic acid, the synthesis of which was enhanced more than 10-fold. Exogenous lysoPtdCho and lysoPtdIns inhibited the incorporation of [14C]arachidonate into TAG in the presence of DAG, and DAG inhibited the incorporation of [14C]arachidonic acid into phospholipids in the presence of lysophospholipids. In general, [14C]palmitic acid was less effectively incorporated into lipids than arachidonic acid. These results suggest reciprocal regulatory effects of DAG and lysophospholipids on acyltransfer to phospholipids and triacylglycerol in brain membranes. PMID- 8439768 TI - Acetylcholine levels, choline acetyltransferase and acetylcholinesterase molecular forms during thyroxine-induced cardiac hypertrophy. AB - The effects of left ventricular hypertrophy induced by hyperthyroidism on three biochemical markers of parasympathetic innervation were investigated. In response to subcutaneous injections of thyroxine (400 micrograms/kg; T4) for 6 days, the left ventricle, but not the right, developed significant hypertrophy (20%). In the enlarged left ventricle, acetylcholine (ACh) content and choline acetyltransferase (ChAT) activity per chamber were elevated approx. 25-30%, although no change in these two markers was evident when the data were expressed per unit wet weight. Immunoblot analysis showed that the relative abundance of ChAT protein increased in the hypertrophied left ventricle in correlation with the increased ChAT activity. No changes in ACh content, ChAT activity and ChAT relative abundance were evident in the right ventricle of T4-treated animals. Although hyperthyroidism did not alter AChE specific activity (per unit wet weight) in the left ventricle, the percent activities of the individual AChE globular forms were affected in this chamber. Specifically, T4-treatment reduced the percent activity of globular (G)4 AChE by 20% and increased that of the combined G1 and G2 AChE pool by 15%. Interestingly, in the hypertrophied left ventricle total AChE activity in its extracellular or functionally-relevant pool was reduced due to a loss of G4 AChE activity. These results show that a compensatory increase in parasympathetic innervation can occur during hyperthyroid-induced left ventricular hypertrophy. However, the reduced activity of the functionally-relevant AChE pool suggests that the clearance of ACh after release may be slowed in the hypertrophied left ventricle. PMID- 8439769 TI - Heterogeneity of the specific imidazoline binding of [3H]idazoxan in the human cerebral cortex. AB - The aim of the present study was to verify whether [3H]idazoxan can be considered as a highly selective ligand for imidazoline preferring receptors (IPR). In human frontal cortex membrane preparations [3H]idazoxan at a low concentration (2 nM) only labelled imidazoline sensitive, catecholamine insensitive sites. Binding was of high affinity, saturable and stereospecific. The rank order of potency of different compounds able to inhibit this binding was cirazoline > (+/-)-idazoxan > guanoxan > (-)-idazoxan > tolazoline > UK-14304 > clonidine. Amiloride, imidazol-4-acetic acid and histamine had no significant affinity for IPR labelled by [3H]idazoxan. [3H]idazoxan bound to 2 different sites (KD1 = 1 nM and KD2 = 16.4 nM). Clonidine behaved as a non competitive, non allosteric inhibitor of [3H]idazoxan binding. Both [3H]idazoxan binding sites were equally affected by clonidine. In membrane preparations obtained from the Nucleus Reticularis Lateralis region (NRL) of the brainstem, [3H]idazoxan binding was similar to that in cortical membranes, particularly with regard to specificity and kinetics. However, in the NRL region binding sites were 4-5 times more numerous than in the frontal cortex. Non linear analyses of saturation data obtained with NRL membrane preparations were compatible with both a one site and a two sites model. No significant effects of 1 mM MgCl2 alone or with 100 microM Gpp(NH)p were observed on either [3H]idazoxan binding or the competition with clonidine or rilmenidine. As in the cortical membrane, clonidine was a non competitive inhibitor of [3H]idazoxan binding to membranes from the NRL region. In conclusion, we show that when a low concentration is used, [3H]idazoxan binding to human brain involves sites almost completely insensitive to catecholamines and specific for imidazolines or related compounds. This binding involves two distinct sites. We also report that [3H]idazoxan imidazoline binding sites are not coupled with a G protein. Because of the non competitive interaction between clonidine and [3H]idazoxan for the binding sites of the latter, we are unable to conclude that the binding sites of the two drugs are identical. However, the non competitive, non allosteric interaction suggests a complex model of multiple binding sites. PMID- 8439770 TI - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) effects on enkephalinergic neurons in various regions of mouse brain. AB - In order to elucidate the effects of MPTP on enkephalinergic neurons, dopamine (DA), norepinephrine (NE), proenkephalin (PE) mRNA and met-enkephalin (ME) were measured in striatum, olfactory tubercle, and prefrontal cortex of C57/B16 mice 1 day-2 weeks following treatment with 96 mg/kg MPTP HCl (24 mg/kg i.p., twice/day for 2 days). DA and its metabolites were depleted 70% in striatum and 40% in olfactory tubercle within 1 day. In cortex, DA was unchanged, whereas homovanillic acid and NE were depleted 50 and 40% respectively by 3 days. ME increased in all three brain regions at different times whereas PE mRNA showed a different pattern in each region, with an increase in olfactory tubercle, a decrease in cortex, and in striatum, a decrease at 1 day followed by an increase at 3 days. Thus enkephalinergic neurons in each region respond differently to MPTP treatment. In striatum and olfactory tubercle. DA is depleted sufficiently to release its tonic inhibition on the enkephalinergic neurons, thereby leading to increased enkephalin synthesis. In cortex, the change in NE metabolism appears to cause a decrease of ME release and thereby a depression of PE synthesis. The possible relationship between these results and the changes observed in Parkinson's disease are discussed. PMID- 8439771 TI - Effects of antidepressant drug treatment on levels of NPY or prepro-NPY-mRNA in the rat brain. AB - The effects of acute and chronic treatment with the tricyclic antidepressant drugs, imipramine, clomipramine and desipramine on levels of neuropeptide Y (NPY) and prepro-NPY-mRNA were studied in different areas of the rat brain. Chronic treatment with imipramine (6.3-25 mg/kg/day) for 10-30 days caused an approx. 15 25% reduction in NPY immunoreactivity in the frontal cortex, but only insignificant changes in striatum, hippocampus, amygdala and hypothalamus. Slight and insignificant changes in the concentrations of prepro-NPY-mRNA were also detected by Northern blot analysis in these brain areas. Only in the hypothalamus was a 20% increase in prepro-NPY-mRNA found. NPY or prepro-NPY-mRNA levels were not altered 3 or 24 h after a single injection of imipramine. The effects of clomipramine and desipramine, at doses of 25 mg/kg daily for 10 days, were investigated in the frontal cortex and in the hippocampus. Except for a slight decrease in prepro-NPY-mRNA in the frontal cortex after desipramine no significant changes in NPY tissue levels or prepro-NPY-mRNA concentrations were observed in the frontal cortex and the hippocampus. In summary, treatment with the three tricyclic antidepressant drugs had no consistent effects on the brain NPY system. These data do not support the previous suggestion that antidepressant drugs may exert their actions by increasing NPY levels in the brain. PMID- 8439772 TI - The asymmetric distribution of phosphatidylcholine in rat brain synaptic plasma membranes. AB - The distribution of phosphatidylcholine between inner and outer monolayers of rat brain synaptic plasma membrane was investigated by means of a phosphatidylcholine specific exchange protein. About 70% of the total membranal phosphatidylcholine was in the outer leaflet, 33% of which was exposed and readily exchanged in intact synaptosomes while the remainder was exchangeable following osmotic shock. Permeabilization of the synaptic plasma membranes by overnight incubation in buffer or by saponin (< 0.08%) exposed an additional 30% of phosphatidylcholine to exchange, presumably from the inner cytoplasmic leaflet. Phosphatidylcholine is therefore asymmetrically distributed in the synaptosomal plasma membrane, as it is in other plasma membranes. PMID- 8439773 TI - Relationships between serotonin induced elevation of intracellular Ca2+ concentration and stimulation of Ca2+ influx in blood platelets. AB - Serotonin (5-HT) caused immediate elevation of intracellular Ca2+ concentration ([Ca2+]i) in blood platelets, and it was completely inhibited by 1 mM EGTA. In Ca2+ replenished platelets, however, 2 mM EGTA did not affect the 5-HT induced elevation of [Ca2+]i when EGTA was applied just before or during the stimulation by 5-HT. At the same concentration 5-HT was also found to enhance Ca2+ influx through the activation of 5-HT2 receptor, but with rather longer latent time. From these results it is suggested that 5-HT induced elevation of [Ca2+]i is caused by mobilization of Ca2+ from intracellular Ca2+ storage sites, but not by direct stimulation of Ca2+ influx. Depletion of such Ca2+ stores might impair the effect of 5-HT on [Ca2+]i. Thus, 5-HT induced augmentation of Ca2+ influx might be secondary to replenishment of the depleted Ca2+ stores which was caused by 5 HT induced internal release of Ca2+. It is concluded that the effects of 5-HT on [Ca2+]i and Ca2+ influx in platelets are manifested sequentially or independently. PMID- 8439774 TI - Subtypes and localization of dopamine receptors in human brain. AB - Dopamine receptors in the human brain play an important role in the pathophysiology and treatment of psychosis and movement disorders. Pharmacological and biochemical studies, and more recently gene cloning techniques, have demonstrated that there are multiple receptors for dopamine in the brain. There is confusion in the literature as new subtypes (D3, D4 and D5 receptors) were classified according to unspecified criteria. At present, however, all subtypes of dopamine receptors that have been identified still fit in the traditional D1/D2 dopamine receptor classification scheme. In this article, a more hierarchical system of nomenclature is proposed and our insights into the distribution and localization of the dopamine receptor subtypes in human brain are summarized. Although the current status of the different subtypes of the D1 and D2 receptor families in human brain remains unclear, their discovery has created hope for the development of more efficacious and specific medicines with less side-effects. PMID- 8439776 TI - Canadian recommendations for the prevention and treatment of malaria among international travellers. PMID- 8439775 TI - Neuroimmune modulation: signal transduction and catecholamines. AB - In recent years, much interest has centered on the commonalities and bi directional interactions between the nervous system and the immune system. This review focuses on mechanisms through which, catecholamines, a class of neuro endocrine molecules, modulate immune functions. Catecholamines can be immune suppressive and inhibit lymphocyte activation of both T and B cells as well as the generation of immune-mediated anti-tumor responses. Some of these catecholamine-regulated activities appear to be modulated through the second messenger, cyclic AMP, whereas others appear to be catecholamine-dependent but cyclic AMP independent. Further delineation of the interacting ligand-receptor complexes, populations of responding cells and signal transduction mechanisms leading to the activation of specifically involved genes and gene products, will lead to enhanced understanding of the integratory functions of the nervous system in immune responses, the biology of stress, the role of stress-associated molecular mechanisms in perturbations of physiological homeostasis and the development of a new biological psychiatry with accompanying rational therapeutic modalities. PMID- 8439777 TI - Microsporidiosis in AIDS patients. PMID- 8439778 TI - National Advisory Committee on Immunization (NACI). Statement on typhoid immunization. PMID- 8439780 TI - Hepatitis A--Newfoundland. PMID- 8439779 TI - Hepatitis A among men in a Canadian correctional facility. PMID- 8439781 TI - Influenza surveillance worldwide. PMID- 8439782 TI - Skin lesions. The GP's view. PMID- 8439783 TI - Skin lesions. The plastic surgeon's view. PMID- 8439784 TI - Impact of confocal scanning optical microscopy on pathological practice. AB - This review outlines some recent advances likely to influence the hospital laboratory practice of light microscopy, a technique that remains the cornerstone of all surgical pathology. The principal advances are confocal scanning optical ('indirect view') microscopy, to which this short account is restricted, and tandem scanning ('direct view') microscopy. PMID- 8439785 TI - Benefits and risks of thrombolytic, anticoagulant and antiplatelet therapies in atrial fibrillation. AB - The decision whether to anticoagulate is a common dilemma when faced with a patient with atrial fibrillation. This article reviews the role of warfarin and antiplatelet agents and recommends a rational approach to the management of this condition. PMID- 8439786 TI - Dental abscess in an anticoagulated patient with ankylosing spondylitis. PMID- 8439787 TI - Management of advanced gynaecological malignancies. AB - The management of patients with advanced gynaecological malignancies remains a therapeutic challenge and relies on careful staging of the disease and individualization of treatment regimes. This article explores the historical and current therapeutic options available for women with disease originating from the vulva, cervix, endometrium and ovary. PMID- 8439788 TI - Priority setting in purchasing. AB - The NHS cannot deliver full comprehensive health care to all the population. In this article the need to define a range of basic health services is emphasized. Agreement on priorities requires ethical, economic and clinical debate. PMID- 8439789 TI - Postoperative shivering. AB - Shivering is common during recovery from anaesthesia. Factors in the aetiology include the use of volatile anaesthetic agents, prolonged anaesthesia, gender and age. The relationship between postoperative shivering and thermoregulation is not clear. Management should include measurement of the patient's temperature. PMID- 8439790 TI - Osteoporotic sacral fracture causing neurological deficit. PMID- 8439791 TI - The rationale behind rationing. PMID- 8439792 TI - Deinstitutionalization and the mentally ill. PMID- 8439794 TI - Terminology and learning disability. PMID- 8439793 TI - Surrogacy: time to heed the patient's views. PMID- 8439795 TI - Salus fidesque animalium. PMID- 8439796 TI - Plasma profiles of albendazole metabolites after administration of netobimin and albendazole in sheep: effects of parasitism and age. AB - Netobimin and albendazole were administered to 3-month-old lambs with moderate infections of Nematodirus battus and to comparable parasite-naive lambs. Albendazole sulphoxide and albendazole sulphone concentrations were determined in the plasma of all lambs at frequent intervals after treatment. Both anthelmintic preparations were 100% effective in reducing nematode faecal egg output in the lambs. There were no significant differences in the concentrations of the sulphoxide or sulphone metabolites in parasitized compared with non-parasitized lambs given the same parent anthelmintic. The parasite-naive lambs were subsequently weaned and maintained indoors in conditions designed to preclude nematode parasite infection until they were 9 months old. Netobimin and albendazole were administered again and the plasma profiles of the albendazole sulphoxide and albendazole sulphone metabolites determined. There were no significant differences in the plasma distribution of these metabolites with age of the lambs. The area under the plasma concentration time curve, mean resident time and apparent half-life of the albendazole sulphoxide metabolite was determined following administration of each parent drug and the clearance of the metabolite/systemic availability of parent drug was determined as a marker of the amount of drug available for metabolism. There were no significant differences in pharmacokinetic variables between parasitized and non-parasitized animals nor with the age of the animals. PMID- 8439797 TI - The application of molecular biology to the study of veterinary infectious diseases. AB - The practical impact that the techniques of molecular biology is having on the study of infectious diseases of veterinary importance is discussed. The areas highlighted include the development of novel diagnostic assays such as the polymerase chain reaction, the use of recombinant antigen in ELISA tests, and the potential of genetically engineered vaccines to alter radically the disease status of animals in developed and developing countries. Novel vaccine strategies such as the use of rationally attenuated viruses as has been successfully employed with pseudorabies virus, and the use of viruses such as vaccinia as vaccine vectors to carry the genes encoding potent immunogens from a range of pathogens (such as rabies and rinderpest) are described. Contributions to the study of epidemiology, mechanisms of pathogenesis and immune responses are also discussed. PMID- 8439798 TI - The uses and limitations of the electroretinogram in veterinary practice. PMID- 8439799 TI - A comparative review of human and equine leucocyte differentiation antigens. AB - Monoclonal antibody technology has allowed the recognition and study of numerous leucocyte antigens in man and laboratory animals for over a decade. Numerous advances in the understanding of immune responses and immunopathology have resulted. In recent years equine researchers have started to develop similar reagents, which now offer a powerful tool to investigators of equine immunology and disease. PMID- 8439800 TI - Culicoides; do vectors respect national boundaries? PMID- 8439801 TI - Progressive retinal atrophy in miniature longhaired dachshund dogs. AB - A form of generalized progressive retinal atrophy unlike other previously recorded canine retinal dystrophies has been investigated in Miniature Longhaired Dachshund dogs. Segregation patterns in litters from matings involving affected individuals were consistent with simple autosomal recessive inheritance. The earliest ophthalmoscopic signs, appearing at approximately 6 months of age and coinciding in some cases with the onset of nyctalopia, included changes in the granular appearance of the tapetal fundus followed by generalized tapetal hyper reflectivity and retinal vascular attenuation; later there was irregular loss of pigment in the non-tapetal fundus and optic atrophy. However, there was marked variation in the age of onset and progression of the disease, even within a single litter. The electroretinogram was normal in waveform and latency in four affected littermates at 10 weeks of age but by 9 months was markedly reduced in amplitude in two pups and virtually extinguished in the others. Significant histological changes at 10.5 weeks of age included thinning of the outer nuclear layer, irregularity and attenuation of the rod photoreceptor outer segments and early disorganization of the rod outer segment disc lamellae. By 25 weeks the photoreceptors were grossly degenerate with short rounded inner segments and only residual amounts of outer segment material remaining. This condition in the Miniature Longhaired Dachshund is later in onset than rod-cone dysplasia in Irish Setters but significantly earlier than progressive retinal atrophy in Tibetan Terriers and progressive rod-cone degeneration in, for example, Miniature Poodles. The condition could therefore serve as a potentially useful model for retinitis pigmentosa in man. PMID- 8439802 TI - Scientific publications from the Animal Health Trust at Newmarket 1942-1991: a veterinary record. PMID- 8439804 TI - Distribution of types of neurons in the optic tectum of the small-spotted dogfish, Scyliorhinus canicula L. A Golgi study. AB - The distribution of neuronal types in the six layers of the optic tectum of the small-spotted dogfish, Scyliorhinus canicula, was studied using Golgi methods. The eight types of neurons have a variable distribution, some of them represented in all six tectal layers. Most neurons of the optic tectum have a radial orientation, and a small portion are disposed horizontally. The relative ratios of the different neuronal types in the six layers indicate that about 80% of the tectal neurons are intermingled with the optic nerve axon terminals in the superficial layers of the tectum. These results corroborate previous reports that the tectum of this selachian species is more specialized than formerly supposed, in spite of the differences in degree of neuropil lamination with other non mammalian vertebrates. PMID- 8439803 TI - The diencephalon and optic tectum of the longnose gar, Lepisosteus osseus (L.): cytoarchitectonics and distribution of acetylcholinesterase. AB - The cytoarchitecture of nuclei in the diencephalon and the distribution of acetylcholinesterase (AChE) in the diencephalon and optic tectum were analyzed in the longnose gar, Lepisosteus osseus, a non-teleost actinopterygian fish. Nuclei were identified in the preoptic area, thalamus, posterior tubercle, hypothalamus, synencephalon, and pretectum which are homologous to like-named nuclei in teleosts and other non-teleost actinopterygians. Of particular note, a nucleus in the rostral diencephalon, nucleus rostrolateralis, which has previously been identified only in the osteoglossomorph Pantodon, is present in the long-nose gar. The posterior pretectal nucleus, previously identified in teleosts and in the bowfin Amia, is also present in gars. The small size of the posterior pretectal nucleus in gars supports the hypothesis that this nucleus was small plesiomorphically. The distribution of AChE in the diencephalon and optic tectum corresponds in most respects to that found in teleosts. The superficial pretectal nuclei, including the posterior pretectal nucleus, are strongly positive for AChE. In contrast, most of the nuclei within the preglomerular complex are negative for AChE. Acetylcholinesterase is present in some of the fibers in the optic tracts and in most retinorecipient nuclei, as well as in some other nuclei and tracts. PMID- 8439805 TI - How are more complex brains different? One view and an agenda for comparative neurobiology. AB - Do more complex brains operate on the same principles as simpler brains, merely employing more of the same; or has evolution produced new principles? A neglected research agenda is the search for relevant differences between brains of animals belonging to different major grades of complexity and cognitive capacity. More complex brains are believed to be capable of more transactions, discriminations, memory and repertoire--functional criteria of 'better' brains. While comparative cognition needs to test these expectations to verify what would be one of the major consequences of evolution, comparative neurobiology needs to discover what, in detail, by all the methods and measures of neuroanatomy, neurophysiology and neurochemistry, is different in more complex brains and which of these differences are relevant to behavioral differences. Formerly it was fashionable to deny differences in the dimension that might be called higher and lower. The criterion of complexity, defined as the number of different parts, processes, interactions and behaviors, may be a useful index of advancement. Unequivocal advancement has occurred between some major taxa, although it is not inevitable. Anatomically, it is clear that novelties have evolved and complexity is more than size or number of the same components. Physiologically, new types of cells, local and larger circuits and emergent properties of assemblies have increased the complexity of operations and organization. It needs to be reasserted that more complex brains have evolved repeatedly, both among invertebrates and among vertebrates, because similar assertions have been incorrectly labeled as 'intuitive scaling' and anthropocentric or moral statements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8439806 TI - Auditory projections to the anterior telencephalon in the budgerigar (Melopsittacus undulatus). AB - The connections of a higher order auditory area in the neostriatum intermedium pars ventrolateralis (NIVL) were mapped with pathway tracing techniques in order to elucidate possible pathways by which auditory feedback may influence vocal learning in the budgerigar (Melopsittacus undulatus). Previous research has shown that NIVL receives projections from Field 'L' as well as adjacent portions of the dorsolateral neostriatum intermedium (NIDL) and hyperstriatum ventrale (HV) and, therefore, may be homologous to previously described auditory centers in the dorsal and lateral portions of the auditory neostriatum of songbirds. The efferent connections of NIVL terminate within a small portion of the rostromedial archistriatum as well as a more rostrally situated area within the medial neostriatum intermedium (NI) and HV. Near by (but not overlapping) fields in NI and HV receive input from the nucleus dorsomedialis posterior thalami (DMP), the archistriatum and ectostriatum. Interestingly, only the DMP projection field overlaps a neural field known to be related to the vocal motor system. The DMP projection field corresponds to that previously described as the magnocellular nucleus of the anterior neostriatum; this nucleus is known to project to the higher vocal center in the budgerigar. In addition to projections from NIVL to medial NI and HIV, auditory information is relayed to the anterolateral telencephalon directly from the brainstem via the ventrolateral nucleus of the lateral lemniscus (VLV). This latter pathway appears comparable to that described in pigeons derived from the intermediate nucleus of the lateral lemniscus. The projection field of VLV overlaps a restricted portion of the caudal and medial aspect of nucleus basalis. These results support the notion that many aspects of telencephalic auditory pathways in birds are primitive characters, although a direct connection between auditory and vocal motor circuits was not found in the present study. PMID- 8439807 TI - Testicular cancer. PMID- 8439808 TI - Prostate cancer. PMID- 8439809 TI - Cancer chemotherapeutic and biologic agents. PMID- 8439810 TI - Cancer chemotherapeutic and biologic agents. PMID- 8439811 TI - The National Cancer Data Base: a cancer treatment resource. PMID- 8439812 TI - Clinical highlights from the National Cancer Data Base: 1993. PMID- 8439813 TI - Trends in prostate cancer care in the United States, 1974-1990: observations from the patient care evaluation studies of the American College of Surgeons Commission on Cancer. PMID- 8439814 TI - Mycosis fungoides: clinical and histologic features, staging, evaluation, and approach to treatment. PMID- 8439815 TI - Influence of Kupffer cell phagocytosis blockade on the production of ovalbumin specific IgE and IgG1 antibodies in an experimental model. AB - The aim of the present study was to evaluate the influence of Kupffer cell phagocytosis blockade (KCPB) on the production of reaginic (IgE) and non-reaginic (IgG1) ovalbumin antibodies in an experimental animal model. Forty-two female heterozygous Gunn rats were injected with two 100 micrograms doses of ovalbumin separated by 13 days, into jugular vein (Group I, n = 10), portal vein (Group II, n = 10), jugular vein with prior KCPB (Group III, n = 10) and portal vein with prior KCPB (Group IV, n = 12). KCPB was induced with gadolinium chloride (5 mg/kg body weight, 24 hr before each ovalbumin administration). Antibodies were determined by passive cutaneous anaphylaxis in sera obtained 12 days after the first dose of ovalbumin and 8 days after the second one. No antibodies were detected at any time in Group II. The maximum response was observed in Group IV in which, after two doses of ovalbumin, 100% of the animals presented IgG1 and 58% presented detectable IgE antibodies. Differences between group IV and the other groups were statistically significant. This phenomenon does not seem to be due to a systemic effect of gadolinium chloride since humoral response was not increased in Group III with respect to Group I. It is concluded that the liver represents a barrier to IgE and IgG1 sensitization. KCPB not only eliminates this barrier, but also clearly increases antibody production to a protein antigen (ovalbumin) arriving at the liver through the portal vein. PMID- 8439816 TI - Characterization of Aspergillus umbrosus carbohydrate antigens by biotinylated lectins and IgG response to mannan/mannoprotein antigens in patients with farmer's lung. AB - Twenty-one different biotinylated lectins were used to recognize the carbohydrates of Aspergillus umbrosus, one of the most common microbes that patients with farmer's lung in Finland are exposed to. The glycoprotein fraction of A. umbrosus was bound especially well by Concanavalin A and consisted mainly of carbohydrates mannose and glucose. The carbohydrate fraction of A. umbrosus antigens were isolated from the crude extract of A. umbrosus with Con A-Sepharose affinity chromatography. Serum IgG antibodies to A. umbrosus mannoprotein fraction were determined in 57 patients with farmer's lung, 10 asymptomatic exposed farmers and 10 healthy controls by enzyme linked immunosorbent assay. Candida albicans and Saccharomyces cerevisiae mannan were used as controls. Patients had high levels, whereas asymptomatic exposed farmers showed moderate, and health controls low levels, of IgG antibodies to the A. umbrosus mannan/mannoprotein fraction. There were no significant differences in the mean antibody levels between the patients and controls against C. albicans or S. cerevisiae mannose fraction although in all groups more antibodies were detected against C. albicans than S. cerevisiae. PMID- 8439817 TI - Elimination diet and intestinal permeability in atopic eczema: a preliminary study. AB - We measured small intestinal permeability to lactulose and rhamnose in 18 healthy children and in 15 children with atopic eczema, before and after a 14-day elimination diet. The children with atopic eczema had higher initial urinary lactulose/rhamnose ratios than the controls. After dietary restriction, there was no overall change in permeability. Dietary therapy did however result in a large reduction in permeability in three of the nine children whose skin disease was improved, but a statistically significant decrease in permeability was not observed in the diet-responsive group as a whole. Larger studies would be required to confirm that dietary restrictions can reduce intestinal permeability in some children with atopic eczema. PMID- 8439818 TI - Effect of murine recombinant interleukin-5 on bronchial reactivity in guinea pigs. AB - We have reported that an intratracheal injection of murine recombinant interleukin-5 (mrIL-5, 15 micrograms/0.25 ml/animal) induces the increased number of inflammatory leucocytes and epithelial cells in bronchoalveolar lavage fluid (BALF) 24 hr after administration of mrIL-5 in guinea-pigs [1]. In this paper, we have examined the effects of mrIL-5 on bronchial reactivity in guinea-pigs. An intratracheal injection of mrIL-5 (15 micrograms/0.25 ml/animal) induced airway hyperresponsiveness to acetylcholine (ACh) which was accompanied with eosinophilia and neutrophilia in blood at 24 hr in guinea-pigs. Bovine serum albumin (BSA, 15 micrograms/0.25 ml/animal) used as a reference material did not cause airway hyperresponsiveness, blood eosinophilia and neutrophilia. Prednisolone (20 mg/kg, i.p.) inhibited mrIL-5-induced airway hyperresponsiveness, eosinophilia and neutrophilia. Ketotifen (2 mg/kg, i.p.) also reduced this airway hyperresponsiveness and neutrophilia but not eosinophilia. In contrast, the injection of 2% disodium cromoglycate (DSCG) into the trachea showed the tendency of inhibitory effects against mrIL-5-induced airway hyperresponsiveness, eosinophilia and neutrophilia. The present data indicate that mrIL-5 induces airway hyperresponsiveness, blood eosinophilia and neutrophilia in guinea-pigs and that prednisolone and ketotifen inhibit mrIL-5 induced airway hyperresponsiveness accompanied with reduction of the increased number of leucocytes, suggesting that eosinophils and neutrophilia in blood may be important for the onset of bronchial hyperresponsiveness caused by mrIL-5 in guinea-pigs. PMID- 8439819 TI - Evidence for chestnut pollinosis in Paris. AB - The existence of chestnut pollinosis in Paris is not generally accepted in spite of the production of very large quantities of chestnut pollen in July. We carried out systematic skin-prick testing with chestnut pollen on 81 patients seen in the allergology department. The results were positive in 17 of the 47 patients presenting seasonal symptoms and in none of the 34 patients with perennial symptoms (chi 2 test = 12.91, P < 0.001). Eight of the 17 positive patients had sIgE levels above 300 IU/ml, 15 had a positive RAST and 14 had a positive nasal provocation test result. On the basis of these findings and the results of the clinical examination during the peak period of pollen emission, we diagnosed chestnut pollinosis in 11 patients. We draw our conclusions from the evidence of this form of pollinosis in the Paris region, together with the reasons why it is, as yet, rarely recognized. PMID- 8439820 TI - Macrophage: dendritic cell interaction in regulation of the IgE response in asthma. PMID- 8439822 TI - Precise area determination of skin-prick tests: validation of a scanning device and software for a personal computer. AB - When skin-prick tests (SPTs) are used quantitatively, the circumference of the weal and/or the flare is outlined using a felt tip pen, and transferred to paper by adhesive tape. The aim of the study was to develop and validate a procedure, objectively and precisely determining these areas after transfer to paper. A system was developed enabling the drawing of the area of weal or flare to be read by a hand-held scanner and calculated on a personal computer. Areas in the 5-500 mm2 range could be determined with day-to-day and interoperator coefficients of variation (CVs) of 3.1% and 1.8%, respectively. Accuracy was determined in two ways: by correlation to cutting/weighing of four times enlarged SPT areas (r2 = 0.999, P < 0.001) and by measuring standardized areas (deviations less than intra assay CV, i.e. 1-2%). For comparison, CV of alternative methods were also determined: eight different areas (9-76 mm2) were evaluated in quadruplicate using the SPT-scanner (CV = 1.4%), by cutting/weighing of paper (CV = 2.3%), by digitizing (CV = 4.4%) or by measuring longest and orthogonal diameters (CV = 13.6%). In conclusion, the scanning device and software provides an objective and reproducible procedure for rapid determination of SPT areas. When areas are determined by scanning, digitizing or cutting/weighing the variations in area determination becomes negligible compared to the variations of the entire skin test procedure. PMID- 8439821 TI - Improvement of food-sensitive atopic dermatitis accompanied by reduced lymphocyte responses to food antigen following natural measles virus infection. AB - Five patients with atopic dermatitis (AD) who were sensitive to hen's egg were observed before and after natural measles virus infection. Within 4 weeks of natural measles virus infection, the eczematous lesions clearly improved in four of the five patients in whom neither offending foods were eliminated, nor anti allergic drugs, systemic steroids and steroid ointment administered. This was accompanied by reduced proliferative responses of peripheral blood mononuclear cells (PBMCs) to ovalbumin (OA). Another patient showed a transient improvement of AD symptoms, from severe to mild, and thereafter returned to severe accompanied by increased proliferative responses of PBMCs to OA. Radioallergosorbent test (RAST) scores for hen's egg in all five patients did not change in each level in each patient, except the transiently decreased RAST scores for hen's egg in one patient, after the infection. Thus, in patients with AD who are sensitive to food, the improvement of AD symptoms that appeared within 4 weeks of natural measles virus infection was related to reduced proliferative responses of PBMCs to the food antigen following the infection. PMID- 8439823 TI - Defining allergens of mammalian origin. PMID- 8439824 TI - Prevention of ventricular remodelling post myocardial infarction: timing and duration of therapy. AB - OBJECTIVE: To review the evidence for the temporal pathophysiological evolution of structural, topographic and functional changes during remodelling post infarction, and how the timing and duration of therapeutic interventions for limiting remodelling might influence outcome. DATA SOURCES: Published English language literature. STUDY SELECTION: The focus was on experimental and clinical studies relating to modification of post infarct remodelling as well as pertinent clinical trials with clinical outcome and mortality end-points. DATA EXTRACTION: An objective determination of the timing and duration of therapy from the indexed infarction, and the rationale for the approach and its possible relation to measured outcome parameters. DATA SYNTHESIS: Several strategies targeted to salvage ischemic myocardium and unload the left ventricle have proven effective in limiting remodelling. Because remodelling begins very early and is a staged and progressive pathophysiological process, timing and duration of therapy are likely to have a profound effect on outcome. Different outcomes can be expected depending on whether therapy is begun very early (during the infarction process), early (after completion of the infarction process but before significant deposition of infarct collagen has occurred), late (after infarct collagen has peaked and infarct healing is completed) or very late (after healing is completed). Different outcomes can also be expected with therapy that spans one or more of these stages. Maximum benefit might be expected from therapy that is begun very early, spans the entire healing process and extends beyond. Two dimensional echocardiograms can be used to assess the impact of therapies on remodelling and function. Very early thrombolysis and low dose intravenous nitroglycerin followed by prolonged angiotensin-converting enzyme inhibition and/or nitrate appear to be a very promising algorithm. CONCLUSIONS: The optimal therapeutic strategy for limiting post infarct remodelling should recognize the pathophysiological staging of the process and be targeted at preventing infarction, early expansion and progressive dilation. PMID- 8439825 TI - Pulmonary edema induced by fluid administration in acquired immune deficiency syndrome patients with cardiac autonomic dysfunction. AB - Two patients with the acquired immune deficiency syndrome developed acute pulmonary edema following intravenous fluid administration. Both recovered with diuretic therapy. In neither case was there evidence of persistent severe left ventricular dysfunction, nor was there evidence (either clinically or by thallium study) of flow limiting coronary lesions or of cardiac uptake of iodine-123 meta iodobenzylguanidine, pointing to ventricular sympathetic neuropathy. It is hypothesized that destruction of the cardiac sympathetics contributed importantly to the development of pulmonary edema following the intravenous fluid load. PMID- 8439826 TI - Vitamin E--then and now. PMID- 8439827 TI - Coronary artery luminal narrowing in the young with sudden unexpected death: a coroner's autopsy study in 350 subjects age 40 years and under. AB - OBJECTIVE: To describe the extent and distribution of coronary artery luminal narrowing in a Canadian population (aged 40 years and under) dying suddenly and unexpectedly. METHODS: From a coroner's autopsy population of 350 subjects whose mean age was 28.4 +/- 6.5 years and of whom 250 were male, percentage luminal narrowing was estimated in the four epicardial coronaries. The left main, left anterior descending, left circumflex and right major coronary arteries were sectioned at 5 mm intervals and percentage cross-sectional luminal narrowing from the internal elastic lamina of each segment was estimated microscopically and then graded into four categories: I, 0 to 25%; II, 26 to 50%; III, 51 to 75%; and IV, greater than 75%. A total of 14,611 5 mm segments were evaluated (mean 41.7 per case). The segments were classified as originating from males or females and into three age groups (less than 20, 20 to 29 and 30 to 40 years). RESULTS: For the entire population, virtually no luminal narrowing greater than 50% was found in patients less than age 20 years, but was found in 3% of segments in the group aged 20 to 29 years and in 8.4% of segments in the group aged 30 to 40 years. In the group aged 20 to 29 years, greater than 50% narrowing was found in 3.8% of segments in males and in 1.2% of segments in females (P < 0.001). In the group aged 30 to 40 years, the corresponding numbers were 10.5% for males and 2.2% in females (P < 0.0001). Eighty-six males (34.4%) had greater than 50% narrowing of at least one coronary artery versus 19 females (19%) (P < 0.01). Left main narrowing of greater than 50% was found in 17 subjects, of which 13 were males. Luminal narrowing was more prevalent in the left anterior descending than the right coronary artery or left circumflex coronary artery and more prevalent in the right coronary artery than the left circumflex coronary artery. CONCLUSIONS: In subjects less than age 20 years, luminal narrowing greater than 50% was virtually nonexistent. Its frequency progressed in both sexes after age 20 years and was significantly more pronounced in males. Narrowing of the left main coronary artery was more frequent than anticipated and was more common in males. PMID- 8439828 TI - The acute and chronic effects of nitrendipine on plasma catecholamines in hypertensive patients. AB - OBJECTIVE: To investigate the acute and chronic effects of nitrendipine on plasma catecholamines in hypertensive patients. DESIGN: The variations in level of plasma noradrenaline and adrenaline were measured in the supine and standing positions before and after the initial dose, and after 12 weeks of nitrendipine therapy. Following a washout placebo period, treatment was initiated by a single 20 mg dose of nitrendipine. This was followed by a double-blind randomization into two groups: one receiving 10 mg nitrendipine twice daily, the other receiving 20 mg once daily. SETTING: Clinical investigation unit, University Hospital (University of British Columbia site), Vancouver, British Columbia. PATIENTS: Sixteen patients (seven males and nine females), mean age 51 years (range 27 to 63), with mild to moderate, uncomplicated hypertension. RESULTS: Two hours after administration of the initial 20 mg nitrendipine dose to all patients, there was a significant fall in the supine and standing systolic and diastolic blood pressure - from 164 +/- 3/102 +/- 1 to 139 +/- 2/87 +/- 2 mmHg, and from 153 +/- 4/105 +/- 1 to 139 +/- 3/90 +/- 1 mmHg, respectively. The supine and standing heart rates were unchanged. After 12 weeks of nitrendipine therapy, blood pressure was reduced (2 h after the dose) to a similar extent as that seen after the initial dose. Acute and chronic nitrendipine administration significantly increased supine and standing noradrenaline, but not adrenaline. Two hours after the initial 20 mg dose, supine noradrenaline increased from 3404 +/- 585 to 4005 +/- 644 pmol/L and standing noradrenaline increased from 3769 +/- 609 to 5821 +/- 615 pmol/L. At the end of the 12 weeks of therapy, similar dose dependent effects were observed 2 h after the dose, but not 12 or 24 h after the dose, in both groups. The percentage increase in noradrenaline produced by nitrendipine in the standing position was consistently greater than in the supine position. CONCLUSIONS: Chronic nitrendipine therapy results in a daily increase in plasma noradrenaline (2 h after the dose), and the effect is greater in the standing position. PMID- 8439829 TI - Effect of ageing on the relationship between early diastolic left ventricular function and mitral valve motion. AB - OBJECTIVE: The relationships between age and diastolic left ventricular function, and age and mitral valve motion were studied. DESIGN: The maximum velocity of circumferential fibre lengthening (negative peak Vcf) of left ventricular function and mitral valve motions, such as mitral valve E and A wave amplitude, D E and E-F slopes, and their relationships were assessed. SUBJECTS: Twenty young, healthy persons (10 males and 10 females) from 20 to 47 years old (mean 34.5), and 26 older healthy subjects (five males and 21 females) from 62 to 94 years old (mean 80.0) were studied. INTERVENTION: M-mode echocardiography of left ventricular function and mitral valve motion were recorded and digitized for the assessment. MAIN RESULTS: Age showed a significant (P = 0.0001) correlation with negative peak Vcf (r = -0.62), with E wave amplitude (r = -0.83), with D-E slope (r = -0.71) and with E-F slope (r = -0.83). Negative peak Vcf was correlated with E wave amplitude (r = 0.51, P = 0.0007), with D-E slope (r = 0.31, P = 0.058), with E-F slope (r = 0.53, P = 0.0005). Its relations with mitral valve A wave amplitude was r = -0.30, P = 0.17 in the elderly group and r = 0.003, P = 0.99 in the younger group. A significant (P < 0.001) positive, linear correlation was observed between age and mitral A/E ratio (r = 0.82). CONCLUSIONS: The easily measurable mitral valve E-F slope and E wave amplitude can be used to assess early diastolic left ventricular function in ageing. Left atrial contraction appears to play a more important role in the elderly, compensating for the decline in early diastolic left ventricular function. PMID- 8439830 TI - Surgery for cardiac tumours: the University of Ottawa Heart Institute experience (1980-91). AB - OBJECTIVE: To review the University of Ottawa Heart Institute's experience with surgery for cardiac tumours. Case series of all patients who had surgical exploration of cardiac tumours from 1980-91 inclusive. Hospital charts, surgical pathology reports, gross photographs and glass microscopic slides were reviewed in each case. SETTING: Tertiary care, specialized cardiac referral centre. PATIENTS: All patients were diagnosed and treated surgically for heart tumours at the University of Ottawa Heart Institute over the 11-year period. The group consisted of 29 adults (14 male, 15 female) aged 15 to 76 years (mean 48) and one male newborn (six days old). Follow-up was available in 24 of 30 cases and averaged three years and four months (range four days to seven years). RESULTS: Twenty-six patients had primary cardiac tumours; 24 were benign (18 myxomas and seven nonmyxomas [one patient with lipomatous hypertrophy had coexistent myxoma]) and two were malignant. Four patients had involvement of the heart by tumours elsewhere: one benign and three malignant. Twenty-two of 24 benign primary tumours were resected successfully with relief of symptoms; two tumours were not resectable. None of the resected benign tumours recurred. Both patients with malignant primary tumours died from their disease. Three of the four patients with tumours arising elsewhere died, while the patient with benign hepatic vein leiomyoma extending into the heart remains well. CONCLUSIONS: Therefore, surgical resection of benign cardiac tumours, whether primary or secondary, is safe and usually curative. Surgery for malignant tumours is diagnostic at best. PMID- 8439831 TI - The role of ambulatory blood pressure monitoring in evaluating hypertensive patients and their treatment. AB - Clinical blood pressure often does not permit estimation of ambulatory blood pressure levels which may be lower than, identical to or higher than office pressure. By providing a substantial number of blood pressure values, ambulatory monitoring decreases subject variability and greatly increases the accuracy of blood pressure measurements. This technique is, therefore, attractive for determining hypertensive patients who would benefit from treatment. Moreover, ambulatory blood pressure measurements correlate well with target organ damage and appear to be a more potent predictor of cardiovascular morbidity and mortality than causal blood pressure. In recent years, ambulatory blood pressure monitoring has proved to be more reliable than measurements in a physician's office when evaluating the efficacy of antihypertensive drugs. It may confirm a fall in blood pressure demonstrated by office measurements and may give valuable information about the antihypertensive effect during specific situations, such as a stressful work setting. Furthermore, ambulatory monitoring is a useful tool for assessing the duration of antihypertensive drug effects. This technique can help to determine whether a once-daily regimen provides 24 h antihypertensive efficacy. Thus, ambulatory blood pressure monitoring is useful in identifying genuinely hypertensive patients who would benefit from treatment, as well as the effects and duration of antihypertensive medications. PMID- 8439832 TI - Risk factors of venous aortocoronary bypass graft disease noted at late symptom directed angiographic study. AB - One hundred and nineteen consecutive patients who had undergone venous aortocoronary bypass surgery 95.1 +/- 46.0 months earlier and in whom symptom directed late graft angiography was performed were studied. Patients were designated 'controls' if their graft(s) appeared intact or revealed only minimal irregularities; they were designated 'cases' if one or several grafts showed at least 25% stenosis or complete occlusion. Controls and cases did not reveal significant differences in the frequency of classic nonlipoprotein risk factors or medication, including the use of acetylsalicylic acid. In multivariate analysis, significant graft narrowing or occlusion was most strongly related to elevated serum apolipoprotein B and lipoprotein(a) levels, as well as to the age of the grafts. PMID- 8439833 TI - Future directions of vitamin E and its analogues in minimizing myocardial ischemia-reperfusion injury. AB - Oxidant injury contributes to myocardial stunning, and cardiac ischemic and reperfusion injury. Vitamin E is the major--and perhaps the only--lipid soluble, chain-breaking antioxidant in the heart. Vitamin E and its analogues potentially offer significant advantages for the prevention of ischemic and reperfusion injury. Recent investigations have suggested that modified vitamin E analogues may be more efficacious than vitamin E and may permit myocardial salvage from acute myocardial ischemic injury. PMID- 8439834 TI - Myocardial infarct size reduction by single high dose or repeated low dose vitamin E supplementation in rabbits. AB - OBJECTIVE: To determine whether myocardial infarct size in rabbits could be reduced by pretreatment with vitamin E, either as a dietary supplement over 10 days or as a single oral dose either 24 or 72 h before coronary artery occlusion and reperfusion. DESIGN: Control and treated rabbits underwent 3 h of coronary artery ligation and 6 h of reperfusion. Region at risk was defined by colloidal carbon and necrosis by triphenyl tetrazolium chloride and light microscopy. Percentage necrosis of the region at risk was determined by planimetry of gross tissue sections by a blinded observer. Analysis of variance and Scheffe's F test compared results. SETTING: The animal research facilities of the Toronto Hospital (General Division). ANIMALS: Adult New Zealand rabbits. INTERVENTIONS: Controls (n = 8) received standard feed; treated groups (n = 8) were given supplemental vitamin E doses of 2000 IU 24 h preoperation (group 24-E), 2000 IU 72 h preoperation (group 72-E) or 200 IU.day-1 for 10 days preoperation (group Lo-E, n = 8). MAIN RESULTS: Percentage necrosis of the region at risk was: control mean, 76.2 +/- 13.0 (mean +/- SD); Lo-E group, 21.8 +/- 10.6; 24-E group, 67.6 +/- 15.1; 72-E group, 47.1 +/- 21.5. Myocardial infarct size was reduced significantly (P < 0.05) versus control in groups Lo-E and 72-E, but not in group 24-E. CONCLUSIONS: Myocardial infarct size in rabbits can be reduced by 10 days of supplemental dietary vitamin E or a single oral dose of vitamin E 72 h before ischemia. The current results suggest possible clinical potential for oral vitamin E to be used as prophylaxis against myocardial ischemia and reperfusion injury. PMID- 8439836 TI - MRI of dorsal mesencephalic lipomas. AB - We detected 23 intracranial lipomas using MRI. Among them were nine pericallosal lipomas, six lipomas at the dorsal surface of the midbrain, and eight in other locations. In this paper, six lipomas at the dorsal surface of the midbrain were analyzed. Five of these lipomas were in the quadrigeminal cistern and one in the left-sided quadrigeminal cistern. Excluding the smallest lipoma, five of the six lipomas had irregular margins and were broadly based on the surface of the midbrain. In these five cases, deformities of the brain parenchyma were observed adjacent to the lipomas. A mildly dilated ventricular system was observed in one of the largest lipomas in a quadrigeminal cistern. Based on their characteristic shapes and locations, we termed them "dorsal mesencephalic lipomas." Thus, the two preferential sites of intracranial lipomas were pericallosal and dorsal mesencephalic. PMID- 8439835 TI - CT diagnosis of rib anomalies, tumors, and infection in children. AB - The computed tomography (CT) findings of 3 patients with Ewing's sarcoma and 10 patients with a variety of benign rib lesions including osteomyelitis, hemangiomatosis, eosinophilic granuloma, aneurysmal bone cyst, neurofibromatosis, enchondroma, and Jarcho-Levin syndrome are presented. CT is of great value in demonstrating characteristic findings of several benign rib lesions. Also, CT accurately shows the destructive pattern of the rib lesion, the presence of pleural effusion, and the local spread of the soft tissue mass. When an aggressive rib lesion with pleural effusion is encountered in an infant or child, Ewing's sarcoma must be excluded unless this lesion has characteristic radiographic findings and a strong clinical history that suggest another diagnosis. The CT findings and differential diagnosis of rib lesions are discussed. Three-dimensional CT well demonstrated the appearance of congenital rib anomalies. PMID- 8439837 TI - Calcified ovarian metastases from mucinous carcinoma of the colon. AB - The authors report a case of calcified ovarian metastases from a mucinous carcinoma of the colon observed in an 85-year-old woman. The radiological aspects observed at computed tomography (CT) are described and the possible mechanisms of tumoral calcifications are discussed. PMID- 8439838 TI - Retroperitoneal ganglioneuroma extending across the midline: MR features. AB - A rare adult case of retroperitoneal ganglioneuroma in which magnetic resonance imaging (MRI) clearly demonstrated unusual extension of the tumor across the midline is reported. Dynamic MR imaging was very useful to distinguish benign ganglioneuroma from other retroperitoneal tumors, especially neuroblastoma and pheochromocytoma. PMID- 8439839 TI - CT diagnosis of concurrent hematomas of the psoas muscle and rectus sheath: case reports and review of anatomy, pathogenesis, and imaging. AB - Two cases are presented in which psoas muscle and rectus sheath hematomas occurred concurrently. The case presentations are followed by a review of anatomy, pathogenesis, and imaging modalities involved in the cause and diagnosis of such hematomas. PMID- 8439840 TI - Lipoma of the falciform ligament: US, CT, and MRI appearances. AB - A case of lipoma of the falciform ligament was demonstrated using computed tomography (CT), ultrasonography (US), and magnetic resonance imaging (MRI). US demonstrated a heterogeneous solid mass anteriorly in the upper portion of the abdomen. CT and MRI revealed a solitary, fatty mass with a small amount of soft tissue in it. PMID- 8439841 TI - Costovertebral erosion with spinal canal encroachment secondary to thoracic aortic aneurysm CT and MR evaluation. PMID- 8439842 TI - Splenic abscess as a complication of septic yersinia: CT evaluation. AB - Yersinia enterocolitica (YE) frequently causes gastrointestinal illness, but is rarely a cause of systemic infection. The complications of septic YE include a wide variety of extraintestinal manifestations, with a 34-50% mortality rate. We present a patient with septic YE complicated by a splenic abscess. The clinical presentation was nonspecific, and the diagnosis of splenic abscess was made by computed tomography (CT). Because of the nonspecific clinical presentation and the wide range of extraintestinal manifestations of septic YE, CT can prove helpful in the diagnosis and management of these patients. PMID- 8439843 TI - Imaging implications in the evaluation of permanent needle acupuncture. AB - Traditional Chinese acupuncture involves placing needles into the subcutaneous tissues along predefined meridians, and later totally removing the needles. A peculiar form of acupuncture exists called "Hari", which involves the permanent placement of fine needles into the subcutaneous tissues. Although this form of acupuncture is uncommon, it is still practiced in both the Orient and the West. Following treatment, the patient's skin is imbedded with hundreds of these fine needles, which remain in the skin for the rest of the patient's life. Several reports have appeared describing their curious radiologic appearance. We present plain films, sonograms, and computed tomography findings of three patients who have undergone this form of acupuncture, and describe their implications in radiographic and clinical evaluation. PMID- 8439844 TI - Post-traumatic sialoceles and mucoceles of the salivary glands. AB - Three cases of post-traumatic sialocele involving the parotid region and one case of post-traumatic mucocele involving the submandibular region are presented. Computed tomography (CT) with contrast showed enhancing borders after a few weeks. Cases earlier than 2 weeks from occurrence showed no enhancement because of the absence of a well-developed capsule. Patients who had the disease longer showed better enhancement of the periphery with contrast because of capsule development. By CT scanning alone it is difficult to differentiated these lesions from other cystic lesions of the face and neck, although certain characteristics like location and rim enhancement may favor one lesion over the other. PMID- 8439845 TI - MRI of intradural-extramedullary spinal neurinomas and meningiomas. AB - The magnetic resonance images of 16 patients with intradural-extramedullary spinal tumors, consisting of 11 neurinomas and five meningiomas were reviewed. The neurinomas appeared hypointense compared to the spinal cord on unenhanced T1 weighted images (T1WI) in nine of 11 patients, and hyperintense on T2-weighted images (T2WI) in nine of 11 patients. Neural foraminal extension was present in two cases. All 10 neurinomas were markedly enhanced; six of them exhibited ring like enhancement on Gadolinium-DTPA (Gd-DTPA)-enhanced T1WI. The meningiomas appeared isointense on unenhanced T1WI in four of five patients and on T2WI in three of four patients. Three meningiomas showed moderate homogeneous contrast enhancement after the intravenous administration of Gd-DTPA. It is concluded that careful scrutiny of magnetic resonance images facilitates the differential diagnosis of spinal neurinomas and meningiomas. PMID- 8439846 TI - MRI of malignant "triton" tumor in a child. AB - We report a case of malignant "Triton" tumor of the right foot in a 5-year-old Caucasian boy with neurofibromatosis. The characteristics and the extent of the tumor were well demonstrated on magnetic resonance imaging. PMID- 8439847 TI - Acalculous cholecystitis (panniculitis) associated with Weber-Christian disease. AB - Acalculous cholecystitis occurred in a patient with Weber-Christian disease. It reflected a panniculitis similar to that which developed in the orbit, abdominal cavity, and the retroperitoneal space. PMID- 8439848 TI - CT, MRI, and angiographic findings of a highly aggressive malignant meningioma. A case report. AB - A case is presented of a highly aggressive malignant meningioma with its associated imaging findings. The case report is followed by a brief review of recognized findings of malignant meningiomas versus their benign counterparts and the accuracy of such findings in differentiating malignant from benign meningiomas. PMID- 8439849 TI - Benign nerve sheath tumor of the sigmoid colon. AB - A rare case of a nerve sheath tumor of the sigmoid colon is presented. The radiological appearance of this tumor is described. The diagnostic roles of ultrasound sonography (US) and the barium enema in differentiating submucosal colon tumors are emphasized. PMID- 8439850 TI - Saccular extracranial carotid artery aneurysm secondary to Behcet's disease. Case report. PMID- 8439851 TI - MRI of intradural spinal arteriovenous fistula associated with ischemia and infarction of the cord. AB - This report presents a patient with an intradural spinal arteriovenous fistula complicated by infarction of the cord. The diagnosis of an arteriovenous malformation was made on the magnetic resonance imaging (MRI) study with the demonstration of intraspinal serpentine areas of low signal intensity (flow voids). The presence of other MRI findings believed to represent spinal cord ischemia included multisegmental swelling of the cord associated with T1 and T2 prolongation and gadolinium enhancement. The location of the malformation, as well as arterial supply and venous drainage, were defined on selective spinal arterial digital subtraction angiography (DSA). Following surgical resection, the clinical condition stabilized, but with poor return of lost function. The repeat MRI 6 months after surgery demonstrated diffuse thoracic cord atrophy. PMID- 8439852 TI - Acute pulmonary hemorrhage. CT evaluation. AB - The computed tomography (CT) scans and chest radiograph of seven patients with bronchoscopic or pathologically proven cases of pulmonary hemorrhage were reviewed to determine the appearance and value of each modality. CT revealed the presence and location in all cases while chest radiographs were falsely negative in two cases. The CT pattern was always an alveolar pattern while the pattern was more variable on chest radiographs. By providing better pattern definition than the chest radiographs, CT is the study of choice in detecting the presence of a suspected pulmonary hemorrhage. PMID- 8439853 TI - The direction of bladder displacement by adnexal masses. AB - Impression on the bladder, or its displacement, indicates the presence of a mass or mass effect. The direction of the displacement aids in the formulation of an appropriate differential diagnosis. We present for discussion two cases in which preoperative lateral bladder displacement was attributed to adnexal masses. When the anatomy of the paravesical spaces is reviewed, it is apparent that lateral bladder displacement is generally not compatible with such masses. PMID- 8439854 TI - Post-traumatic synovitis presenting as a mass in the suprapatellar bursa of the knee. MRI appearance. AB - A lobulated mass in the suprapatellar bursa of the knee is presented with MRI findings simulating the features of focal pigmented villonodular synovitis (PVS). Microscopic examination demonstrated a nonspecific, inflammatory mass of hypertrophied synovium. The MRI features of various forms of synovitis are reviewed from recent literature and differential considerations of a suprapatellar, intrabursal mass are discussed. PMID- 8439855 TI - A 14-month-old HIV-positive female with a 2-day history of fever and vomiting. PMID- 8439856 TI - Oculopharyngeal muscular dystrophy. PMID- 8439857 TI - Correction of blepharoptosis in oculopharyngeal muscular dystrophy: review of 91 cases. AB - Oculopharyngeal muscular dystrophy is a progressive, hereditary myopathy in which the levator palpebrae and the pharyngeal muscles are selectively involved. Progressive, usually symmetric blepharoptosis with or without dysphagia appears in the fifth decade. The high prevalence of this myopathy in Quebec stems from the immigration of a single couple from France in 1634, whose numerous descendants manifest its autosomal dominant heredity. We review our experience in 91 cases over 20 years. The ptosis was moderate in 83% of the cases at the time of surgery, and the average age was 65 years. Beard's surgical guidelines for correction of ptosis based on the degree of ptosis and residual levator function were applied directly in cases of primary intervention, with consistently satisfactory results. This is in contrast to other types of hereditary myopathic ptosis, in which the guidelines must be modified. The rate of recurrence of ptosis among patients followed for at least 9 years was 13%. PMID- 8439858 TI - Surgical results and pathological findings in the oculopharyngeal dystrophy syndrome. AB - The oculopharyngeal dystrophy syndrome is an autosomal dominant disorder commonly seen in patients of French-Canadian descent. The syndrome is characterized by progressive ptosis and dysphagia, with onset in midlife. In this series 26 patients (47 eyelids) underwent surgery to correct the ptosis. The aponeurotic advancement technique, performed in 28 of the lids, resulted in an average elevation of 2.5 mm (mean follow-up interval 8.6 months). The combined aponeurosis-Muller's muscle advancement technique, performed in 17 lids, resulted in an average elevation of 3.5 mm (mean follow-up period 8.0 months). Muller's muscle as well as the levator muscle was found to be involved in the dystrophic process. PMID- 8439859 TI - Complications of retinotomies for subretinal fluid drainage. AB - We reviewed 287 cases of pars plana vitrectomy performed between January 1985 and June 1990 in which retinotomies were created for drainage of subretinal fluid or blood. We found subretinal neovascularization associated with the retinotomy site in two cases (1%) and focal proliferative vitreoretinopathy associated with the retinotomy site in seven cases (2%). These complications were more likely to occur with retinotomies made within the superior macular region (p = 0.002). PMID- 8439860 TI - High-frequency radio wave electrosection of full-thickness eyelid tissues. AB - The Ellman Surgitron, commonly used in dermatology practice, is an electrosurgical instrument with a high-frequency waveform that is modified by filtering and undamping the current so that an almost pure cut is possible, yet with a small amount of coagulation. This device was used in six patients undergoing full-thickness eyelid resection (unilateral in three and bilateral in three) for involutional entropion or ectropion. Nine lid margins were cut with scissors, and nine with the electrosurgical instrument. The latter was found to cause minimal tissue damage and to modify the superficial epithelial cell layer very slightly, without causing it to slough. The tissue was cut cleanly, with less bleeding than occurred with scissors incision. PMID- 8439861 TI - Screening for diabetic retinopathy: changes in direction? PMID- 8439862 TI - Totally asymptomatic inferior oblique overaction. AB - Seventeen children were demonstrated to have completely asymptomatic overaction of one or both inferior oblique muscles. None had a constant vertical deviation in primary position, up gaze or down gaze, and significant patterns were absent. None had diplopia or complaints of torsion. The Bielschowsky head tilt test gave a negative result in all cases. No patient showed excyclorotation on fundus examination. Long-term follow-up (28 to 134 [average 75.6] months) of 13 of the patients showed that the condition did not worsen with time and may not require surgical weakening of the inferior oblique muscle. PMID- 8439863 TI - Iris cavernous hemangioma in a patient with recurrent hyphema. AB - A 41-year-old woman presented with a hyphema in her right eye. Clinical examination revealed a vascular lesion of the iris that had enlarged over a 6 month period. The patient had no other evidence of ocular or cutaneous vascular malformations. Subsequently she experienced recurrent episodes of spontaneous hyphema, and there was objective evidence of growth of the lesion. Consequently, the lesion was excised by means of a sector iridectomy. Histopathological examination showed several large vascular compartments separated by thin, fibrous septa and lined by endothelium, consistent with a cavernous hemangioma. A benign iris melanocytic lesion was identified adjacent to the cavernous hemangioma. The intraocular pressure in the affected eye remained normal after the lesion was removed. After 6 months of follow-up no new hyphemas had developed. Iris cavernous hemangioma should be added to the differential diagnosis of recurrent hyphema. PMID- 8439864 TI - Spontaneous hyphema in an infant with Christmas disease. AB - A 4-month-old boy presented with an apparently spontaneous uniocular hyphema as the initial manifestation of Christmas disease (hemophilia B). Although it is uncommon for patients with hemophilia to experience major bleeds in infancy, and the ocular involvement is usually limited to periocular hemorrhages, we recommend that a coagulation profile be obtained in all patients with intraocular hemorrhage to rule out this disease. PMID- 8439865 TI - Use of ophthalmologic services by diabetic patients in Nova Scotia. AB - To evaluate the possible public health consequences of diabetic retinopathy in Nova Scotia, we investigated the number and frequency of ophthalmologic examinations in patients with diabetes mellitus. A total of 36,683 people (4.2%) were identified from the administrative database of the provincial health department as having a diagnostic code of diabetes during the period March 1987 to February 1990. All billings by ophthalmologists for these patients during the same period were then identified. Of the 36,129 patients aged 10 years or more, 17,518 (48.5%) had seen an ophthalmologist at least once during the study period, and 5218 (14.4%) had seen an ophthalmologist approximately annually. Increased age and being female were associated in univariate logistic regression analysis with higher use of ophthalmologic services. The medical insurance system is free of direct costs to patients, and there are enough ophthalmologists to meet patient needs (4.35 per 100,000 population). The findings indicate that most diabetic patients in Nova Scotia are not seen at least once a year, as recommended by the Expert Committee of the Canadian Diabetes Advisory Board, despite ready availability of ophthalmologic care. PMID- 8439866 TI - Seasonal changes in the adherent microflora of the rumen in high-arctic Svalbard reindeer. AB - Seasonal changes in bacterial colonization of the epithelial tissue were examined in the rumen of high-arctic Svalbard reindeer. Samples of tissue were collected from eight sites in the rumen of reindeer during summer and winter and bacterial colonization was examined using scanning and transmission electron microscopy. At two of these sites, colonization by adherent bacteria was estimated to cover approximately 30% of the ruminal epithelium in specimens collected from reindeer during summer. Bacteria at these sites resembled Ruminococcus sp. and were surrounded by large amounts of glycocalyx. In winter specimens, less than 10% of the epithelial surface was covered by adherent bacteria. Those bacteria that did colonize the epithelial surface were smaller and had virtually no glycocalyx on their surface. Bacteria attached to plant cell wall material in summer samples of reindeer ingesta contained large intracellular glycogen deposits, whereas feed particle-associated bacteria in ingesta collected in winter contained no intracellular glycogen. These data demonstrate that the ruminal bacterial population responds to seasonal changes in feed intake and quality. It is yet to be determined if these bacterial changes enhance the ability of Svalbard reindeer to survive in the hostile environment of the high Arctic. PMID- 8439867 TI - Outer membrane proteins from Serratia marcescens. AB - The outer membrane proteins (OMPs) of several strains of Serratia marcescens have been studied by sodium dodecyl sulphate - urea - polyacrylamide gel electrophoresis. Four major OMPs, named Omp1, Omp2, Omp3, and OmpA (42, 40, 39, and 37 kDa, respectively), have been visualized. The relative proportions of Omp2 and Omp3 depend on cultural conditions (temperature of incubation, osmolarity, and nutrient availability). PMID- 8439868 TI - Mannosyl transfer in Cryptococcus neoformans. AB - A particulate enzyme preparation from Cryptococcus neoformans transferred the mannosyl residue from GDP-mannose to an acceptor consisting of a commercial preparation of methyl 3-O-alpha-mannopyranosyl-alpha-mannopyranoside (containing 10% 2-O-alpha-mannopyranosyl-alpha-mannopyranoside). The configuration of the new bond was alpha by its susceptibility to alpha-mannosidase; the amount of product was dependent on the concentration of enzyme, of GDP-mannose, and of acceptor. The optimal temperature and pH were 37 degrees C and 7.0, respectively. Manganous ion was required for activity and acetyl coenzyme A was stimulatory. Studies suggested that dolichyl phosphate intermediates were not involved in this mannose transfer. The fact that none of the several acapsular mutants tested were deficient in this mannosyltransferase suggested that this enzyme was not involved in synthesis of backbone mannan linkages in capsular polysaccharide. NMR analysis of the methylmannotriose product showed only alpha(1-->2) linkages between sugar moieties. This mannosyltransferase evidently extends alpha(1-->2) mannan by adding another alpha(1-->2)-linked mannosyl residue. Its activity is appropriate for a role in synthesis of "high mannose" oligosaccharide moieties of glycoproteins. PMID- 8439869 TI - Characterization of bacteria isolated from a bleached kraft pulp mill wastewater treatment system. AB - Water samples from the wastewater treatment system of a bleach kraft mill and from the river that supplies the mill were plated on six different media and culturable isolates were screened for substrate utilization patterns, taxonomic characters, plasmid content, and resistance to ampicillin, streptomycin, kanamycin, tetracycline, naldixic acid, mercury, nickel, copper, cobalt, cadmium, and zinc. A cluster analysis of the substrate utilization profiles and taxonomic characters revealed that Pseudomonas, Acinetobacter, and Acidovorax spp. were common among the culturable isolates from the river, while Ancylobacter aquaticus, Klebsiella spp., and an unknown group of pleomorphic Gram-negative methylotrophs were common among the culturable isolates from the mill treatment system. Of isolates from the settling pond and aerated lagoon, 78 and 64% carried plasmids, while only 56% of isolates from the river carried plasmids. Plasmids were significantly associated with resistance to cadmium but not with any other resistance characters. Large numbers of plasmid-carrying A. aquaticus strains and pleomorphic methylotrophs accounted for high plasmid incidence levels in the mill treatment system, and the ability to dechlorinate simple aliphatic substrates was found in these two groups as well as in one Pseudomonas strain. PMID- 8439870 TI - Cloning of a xylanase gene from the ruminal fungus Neocallimastix patriciarum 27 and its expression in Escherichia coli. AB - An endo-beta-1,4-xylanase gene was cloned from Neocallimastix patriciarum 27 in the bacteriophage vector lambda gtWES lambda B and was subcloned into the plasmid vectors pUC18 and pUC19 in which xylanase activity was expressed in both orientations. The xylanase was located in the periplasmic space of the host, Escherichia coli HB101. The pH and temperature optima for periplasmic xylanase activity were 6.2 and 40 degrees C, respectively, and the Km for oat spelt xylan hydrolysis was 0.89 mg.mL-1. It also exhibited hydrolytic activity on carboxymethyl cellulose that was equivalent to 28% of the activity exhibited by the enzyme on xylan. It bound to crystalline cellulose, but lacked hydrolytic activity on amorphous cellulose. SDS-PAGE followed by zymogram analysis showed active bands of 68, 58, and 51 kDa. Isoelectric focusing in gels combined with zymogram analysis showed one band of xylanase activity with a pI of 3.6. PMID- 8439871 TI - The mitochondrial genome of the entomopathogenic fungus Beauveria bassiana: analysis of the ribosomal RNA region. AB - The 28.5-kbp mitochondrial (mt) genome from the entomopathogenic fungus Beauveria bassiana was studied using restriction enzyme analysis, gene probe hybridization, and DNA sequence comparisons. A detailed restriction enzyme map allowed cloning of the entire genome into a number of segments. Hybridization of heterologous gene probes to the mtDNA resulted in the identification of the large ribosomal RNA (lrRNA) and small ribosomal RNA (srRNA) genes. Gene probes derived from several yeasts and fungi failed to identify any additional genes. However, partial DNA sequence analysis revealed the lrRNA and srRNA genes as well as four protein-encoding genes: the NADH dehydrogenase subunit 1 (NAD1), NADH dehydrogenase subunit 6 (NAD6), cytochrome oxidase subunit 3 (CO3), and ATPase subunit 6 (ATP6) genes. The ATPase subunit 9 (ATP9) gene was not identified by hybridization to mtDNA, but could be detected by hybridization to total cellular DNA. The portions of the genes sequenced were homologous to the equivalent genes from yeast and other filamentous fungi, most notably Aspergillus nidulans. No introns were identified in these regions. The organization of the sequenced region of the B. bassiana mt genome more closely resembled that of A. nidulans than that of Podospora anserina or Neurospora crassa. PMID- 8439872 TI - Partial purification and characterization of two extracellular N-acetyl-D glucosaminidases produced by the entomopathogenic fungus Beauveria bassiana. AB - Beauveria bassiana grown in a liquid medium containing N-acetyl-D-glucosamine and colloidal chitin produced two distinct N-acetyl-D-glucosaminidases, NAGase 1 and NAGase 2. NAGase 1 had a molecular weight of 97,000 and NAGase 2 was comprised of two subunits, of molecular weights 64,000 and 66,000. The optimal temperature and pH for NAGase 1 were 57 degrees C and pH 5 and for NAGase 2 they were 37 degrees C and pH 5. NAGase 1 was more thermostable than NAGase 2. The isolectric points of NAGase 1 and 2 were ca. pH 9.5 and 5.5, respectively. NAGase 1 and 2 were unaffected by a 10 mM concentration of chloride salts of the ions Ca2+, Mg2+, or Zn2+, by 10 mM EDTA, and by 0.25-1 mM of short chain fatty acids. Dithiothreitol caused some inactivation of NAGase 2 while stimulating activity of NAGase 1. NAGase 1 had a Km of 0.38 mM and a Kcat/Km of 3923.88 M-1.s-1.NAGase 2 had a Km of 2.095 mM and a Kcat/Km of 411.88 M-1.s-1 when p-nitrophenyl-beta-N acetylglucosaminide was used as the substrate. PMID- 8439873 TI - Use of bacteriophage for the selective isolation of thermophilic actinomycetes from composted eucalyptus bark. AB - A method was developed to reduce the numbers of thermophilic bacteria on isolation plates, which in turn facilitated the detection and isolation of thermophilic actinomycetes. The method involves exposing the test material to bacteriophage suspensions prior to inoculation on isolation plates. This method was applied to composted eucalyptus bark samples, which were then inoculated on R8 and 1/2 TSA + 0.2% casein hydrolysate agar plates. The phage susceptibility of thermophilic bacteria provided a selective means of reducing their numbers on isolation plates and hence increased the numbers of Thermomonospora, Saccharopolyspora rectivirgula, and thermophilic Streptomyces spp. on these media in comparison with the numbers recorded from control plates. PMID- 8439874 TI - Sporocidal properties of peracetic acid and hydrogen peroxide, alone and in combination, in comparison with chlorine and formaldehyde for ultrafiltration membrane disinfection. AB - The sporocidal properties of peracetic acid, hydrogen peroxide, chlorine, and formaldehyde were compared in vitro using a dilution-neutralization micromethod. A combination of peracetic acid and hydrogen peroxide was also tested to assess their interactions. The activities of these agents, which are widely used as disinfectants, were evaluated against Bacillus spore isolates found on stored membranes and collection cultures. Peracetic acid and chlorine exhibited an excellent antimicrobial activity, with a destruction of 10(5) spores/mL after 5 min of contact. Generally the effects of the biocides tested were time dependent. The sporocidal activities of hydrogen peroxide and formaldehyde were the lowest. The combination of peracetic acid and hydrogen peroxide, tested by a checkerboard micromethod, was found to be synergistic. The minimal sporocidal concentration (MSC) was established in terms of time for each biocide. The lowest MSC values for peracetic acid, hydrogen peroxide, chlorine, and formaldehyde were 168-336 ppm (1-2 h of contact), 5625-11250 ppm (5-7 h), 168-336 ppm (2-3 h), and 1875 3750 ppm (5-30 min), respectively. The MSC of a biocide combination of peracetic acid and hydrogen peroxide showed that synergy was maintained with increasing contact time and that the MSC could be reduced by two to eight times when compared with those of the biocides alone. Optimal concentrations and contact times of those chemicals that were promising in vitro were then tested for their ability to disinfect ultrafiltration membranes. The sporocidal activities of peroxide compounds and chlorine were confirmed and the synergism between peracetic acid and hydrogen peroxide was also maintained.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8439875 TI - Regulation of extracellular N-acetyl-D-glucosaminidase production in the entomopathogenic fungus Beauveria bassiana. AB - The entomopathogenic fungus Beauveria bassiana produces two extracellular N acetylglucosaminidases (NAGase) in liquid medium containing colloidal chitin as the sole source of carbon and nitrogen. To study the regulation of NAGase synthesis, N-acetyl-D-glucosamine (GlcNAc), glucose NH4NO3, or amino acids were added to the colloidal chitin medium and NAGase activity was measured. NAGase synthesis was (i) induced with GlcNAc, and no repression was observed with GlcNAc provided at 2% (w/v); (ii) repressed in the presence of glucose plus NH4NO3; (iii) partially repressed when glucose or NH4NO3 was provided; and (iv) repressed to levels that were < 40% of the control levels when glutamic acid, tyrosine, arginine, proline, valine, and histidine were provided to the colloidal chitin medium. Total NAGase activity levels were > 60% of the control activity when alanine, glycine, isoleucine, aspartic acid, and leucine were tested. It appears that synthesis of NAGase is sensitive to cell energy and the carbon and nitrogen requirements. PMID- 8439876 TI - Changes in the rumen microbial population and its activities during the refaunation period after the reintroduction of ciliate protozoa into the rumen of defaunated sheep. AB - Changes in the microbial populations, their activities, and the ruminal fermentation were monitored for 50 d following the reintroduction of ciliate protozoa into four defaunated sheep. A protozoal population was reestablished successfully in each recipient, using a washed inoculum containing approximately 10(3) cells, although there were between-animal differences in the rates of recolonization and genus establishment. Entodinium spp. predominated in the initial stages of the refaunation period and had an apparent maximal generation time of 9-10 h. Bacterial and fungal numbers did not decline following the reintroduction of protozoa and a small transient increase in the numbers of amylolytic and xylanolytic bacteria and fungal zoospores occurred in the early stages of refaunation when the protozoal population was < 10(5)/g ruminal contents, but these subsequently declined as the protozoa established. Although the fibrolytic bacterial population was lowest in period 3 (> 10(5) protozoa/g), the in sacco ruminal digestion of Lolium perenne hay and polysaccharolytic enzyme activities in the solids-associated populations were either maintained or increased when protozoa were present confirming the important contribution of protozoa to fibre breakdown in the rumen. Significant changes in ruminal microbial activities occurred after protozoal reinoculation but before the rumen had refaunated completely. Arylamidase activities in the liquor-phase population and ruminal ammonia concentrations increased significantly within 48 h of transfaunation; the magnitude of the effects became more pronounced as the protozoal population developed. However, volatile fatty acid formation and ruminal pH were not affected after the reintroduction of protozoa. PMID- 8439877 TI - An "all-purpose" cellulase reporter for gene fusion studies and application to the paracrystalline surface (S)-layer protein of Caulobacter crescentus. AB - The secreted endoglucanase (CenA) from the Gram-positive bacterium Cellulomonas fimi and a deletion derivative (delta CenA) lacking the N-terminal leader peptide of native CenA were used to explore the potential of delta CenA as a reporter molecule in Caulobacter crescentus. Expression of cenA in C. crescentus yielded extracellular endoglucanase activity, suggesting that the N-terminal leader peptide of CenA could direct the enzyme to the periplasm where it subsequently leaked into the medium. In contrast, expression of delta cenA yielded only cell associated endoglucanase activity; this suggested that the enzyme retained activity in the C. crescentus cytoplasm. Using the putative cytoplasmic and periplasmic forms of delta CenA as markers, a simple assay for periplasmic delta CenA hybrids was developed. This assay indicated that delta CenA activity was largely independent of cellular location. To facilitate the use of delta CenA as a reporter, a broad host range translational fusion vector (pEC215) incorporating delta cenA was constructed. This vector was used to investigate factors important to the expression of the gene (rsaA) encoding the paracrystalline surface protein (S-layer) of the bacterium. It was found that altering the 5' untranslated region of the rsaA mRNA reduced gene expression by 70%. One rsaA:delta cenA gene fusion resulting from these experiments that incorporated only rsaA translation initiation information was further modified to serve as a general reporter for creating transcriptional gene fusions with other promoters. Gene fusions between alkaline phosphatase (phoA) and either cenA or lacZ were used to supplement information about RsaA secretion derived from rsaA:phoA gene fusions. It was found that linkage of the N-terminal leader peptide of CenA to PhoA yielded 50 100 times more cell-associated PhoA activity in C. crescentus than linkage of the RsaA N terminus. Taken together, these experiments indicated that delta CenA was useful for tagging proteins localized to the cytoplasm, exported to the periplasm, or secreted from the cell, as well as for monitoring events in the cytoplasm such as examining factors important to the level of gene expression. Further, because delta CenA was active in all cell compartments, it could be used to estimate the efficiency of hybrid protein export-secretion from enzyme activity measurements alone. In short, delta CenA possessed many of the attributes of an "all-purpose" reporter. PMID- 8439878 TI - To screen or not to screen. PMID- 8439879 TI - To screen or not to screen. PMID- 8439880 TI - Consultation protocol. PMID- 8439881 TI - Karoshi and smoking. PMID- 8439882 TI - Bursaries for native medical students. PMID- 8439883 TI - Four decades of glucocorticosteroid immunosuppression. PMID- 8439884 TI - We should consider some new approaches to addiction. PMID- 8439885 TI - We should consider some new approaches to addiction. PMID- 8439886 TI - When is a market not a market? PMID- 8439887 TI - Toward integrated medical resource policies for Canada: 12. Looking back, looking forward. PMID- 8439888 TI - Effect of generic drug competition on the price of prescription drugs in Ontario. AB - OBJECTIVE: To analyse the potential effect of generic drug competition on prices in Ontario to assess the costs and benefits associated with Bill C-22 (An Act to amend the Patent Act). DESIGN: Comparison of the cost of the least and most expensive versions of all products sold by more than one manufacturer in 1991. The number of brand-name and generic drug companies marketing each of the products was recorded. RESULTS: Of 1599 products 437 (27.3%) were made by more than one company. Almost half (44.6%) of the 437 were sold by two companies. The more companies that sold a drug the greater the difference in price between the least and most expensive versions. Similarly, as the proportion of generic drug companies in competition increased, the greater the price difference. When competition was between generic drug companies only, the price spread was smaller than when it was between brand-name drug companies only. CONCLUSIONS: Generic drug competition can result in savings to the Ontario Drug Benefit Plan. A more in-depth analysis of the potential savings is necessary to fully assess the costs and benefits associated with Bill C-22. PMID- 8439889 TI - Prevalence of non-insulin-dependent diabetes mellitus and impaired glucose tolerance in two Algonquin communities in Quebec. AB - OBJECTIVE: To assess and compare the prevalence of non-insulin-dependent diabetes mellitus (NIDDM) and impaired glucose tolerance (IGT) in two native Indian communities. DESIGN: Population-based study. SETTING: Two Algonquin communities in Quebec: River Desert and Lac Simon. PARTICIPANTS: All native Indian residents aged at least 15 years were eligible; 621 (59%) of them volunteered to enroll in the study. The participation rate was 49% in River Desert and 76% in Lac Simon. MAIN OUTCOME MEASURES: Fasting blood glucose level and serum glucose level 2 hours after 75-g oral glucose tolerance test, as described by the World Health Organization, in all subjects except those with confirmed diabetes. Other measures included body mass index (BMI), fat distribution and blood pressure. MAIN RESULTS: The age-sex standardized prevalence rate of NIDDM was 19% in Lac Simon (95% confidence interval [CI] 16% to 21%); this was more than twice the rate of 9% in River Desert (95% CI 7% to 11%). The IGT rates were comparable in the two communities (River Desert 5%, Lac Simon 6%). NIDDM and IGT were uncommon under the age of 35 years. Only in Lac Simon was the NIDDM prevalence rate significantly higher among the women than among the men (23% v. 14%); almost half of the women aged 35 years or more had diabetes. In Lac Simon the rate of marked obesity (BMI greater than 30) was significantly higher among the women than among the men (37% v. 19%; p < 0.001); this sex-related difference was not found in River Desert (rates 31% and 23% respectively). Previously undiagnosed NIDDM accounted for 25% of all the cases. NIDDM and IGT were significantly associated with high BMI, sum of skinfold thicknesses and waist:hip circumference ratio (p < 0.001). The subscapular:triceps skinfold ratio, however, did not display such an association, nor did the age-adjusted systolic blood pressure. CONCLUSIONS: The prevalence of NIDDM is high in Algonquin communities and may vary markedly between communities. Although widespread, particularly in women, obesity cannot entirely explain the much higher rate of NIDDM in Lac Simon. Family and lifestyle risk factors, in particular diet and activity patterns, are being analysed in the two communities. PMID- 8439890 TI - Isoniazid toxicity with cerebellar ataxia in a child. PMID- 8439891 TI - Vital statistics--what they teach. 1919. PMID- 8439892 TI - Catholic hospitals strive to retain religious focus in an increasingly secular country. PMID- 8439893 TI - MDs' open letter criticizes CMPA advice on sexual abuse issue. PMID- 8439894 TI - "Plastic surgery tourism" proving a boon for Costa Rica's surgeons. PMID- 8439895 TI - The last great health disciplines turf war, 1990-2020. PMID- 8439896 TI - Medical care in remote areas. PMID- 8439897 TI - Another advantage of breast-feeding. PMID- 8439898 TI - Environmental medicine. PMID- 8439899 TI - Tobacco and denial. PMID- 8439900 TI - Where is the evidence? PMID- 8439901 TI - Where is the evidence? PMID- 8439902 TI - Lovastatin and cholestasis. PMID- 8439903 TI - Where is the evidence? PMID- 8439904 TI - Argentina's health care system. PMID- 8439905 TI - Diagnostic testing in chronic urticaria and angioedema. PMID- 8439906 TI - Guiding STARS. PMID- 8439907 TI - Near-death experience denied. PMID- 8439908 TI - The wicked womb. PMID- 8439909 TI - Clinical practice guidelines: between science and art. PMID- 8439910 TI - Community care for the elderly: is it really better? PMID- 8439911 TI - Hysteria, or "suffocation of the mother". AB - OBJECTIVE: To understand or explain the surprising adherence of prominent physicians throughout the centuries to terms suggesting that the womb could move and cause suffocation, choking or difficulty in swallowing. DATA SOURCES: Hippocratic writings on hysterical symptoms and the views of subsequent authors and contexts surrounding such views. DATA SYNTHESIS: Physicians who followed Hippocrates repeatedly related difficulties in breathing or choking and difficulties in swallowing to the uterus, although most recognized that the womb did not rise out of the pelvis, except partially, when enlarged by pregnancy. Respiratory and gastrointestinal symptoms were often associated with anxiety. The effects may have been attributed to the womb, because it was recognized that the womb, when enlarged, can cause difficulty in breathing. Anxiety was also reported more often in women and may have been attributed to the womb for that reason. CONCLUSION: The suffocation of the mother can be understood as anxiety with dyspnea, and globus hystericus reflects anxiety with a choking sensation or difficulty in swallowing. PMID- 8439912 TI - Are physicians changing the way they practise obstetrics? AB - OBJECTIVE: To examine trends in obstetric interventions in women at low risk over approximately 3 years. It was postulated that there would be a general reduction in most intervention rates. DESIGN: Retrospective review of hospital records. SETTING: Three downtown hospitals of the University of Toronto, in which academic and nonacademic family physicians and obstetricians practised. PATIENTS: A total of 2365 women in phase 1 (April 1985 to March 1986) and 1277 in phase 2 (May to September 1988) met the inclusion criteria for grade A (pregnancy at no predictable risk) of the Ontario Antenatal Record at the time of admission to hospital. OUTCOME MEASURES: Rates of artificial rupture of the membranes, induction, augmentation, epidural anesthesia, continuous electronic fetal monitoring (EFM), instrumental delivery, episiotomy and cesarean section. RESULTS: The family physicians and the obstetricians had significant decreases (p < 0.01) over time in the rates of episiotomy, especially mediolateral, and low forceps delivery. The rate of epidural anesthesia decreased significantly in the obstetrician group. The rates of artificial rupture of the membranes, induction and continuous EFM increased in the two physician groups; the increased rate of EFM was significant in the obstetrician group (p < 0.01). There was no significant change in the rates of augmentation, midforceps delivery, vacuum extraction or cesarean section. All of the trends were found to hold when the intervention rates were analysed according to the women's parity. CONCLUSIONS: Some of the findings reflect recommendations and trends reported in the literature, whereas others are not supported by clear medical evidence. The unpredictable nature of the trends suggests that further study is warranted of the reasons for obstetric trends and for the changes in physicians' practice patterns. PMID- 8439913 TI - Concerning old age. 1927. PMID- 8439914 TI - Some opinions on longevity. 1954. PMID- 8439915 TI - When considering attacks against the National Breast Screening Study, consider the sources. PMID- 8439916 TI - Clinical practice guidelines: weapons for patients, or shields for MDs? PMID- 8439917 TI - Report calls for major changes in drug-approval process, but will they be implemented? PMID- 8439918 TI - Researchers, physicians paying more attention to weather's impact on health. PMID- 8439919 TI - The patient behind the veil: medical culture shock in Saudi Arabia. PMID- 8439920 TI - The bigger slice of the pie? PMID- 8439921 TI - The bigger slice of the pie? PMID- 8439922 TI - The bigger slice of the pie? PMID- 8439923 TI - The bigger slice of the pie? PMID- 8439924 TI - The bigger slice of the pie? PMID- 8439925 TI - Organ and tissue transplantation. PMID- 8439926 TI - Sulfite-containing pharmaceuticals. PMID- 8439927 TI - Drug nomenclature: suggestions for change. PMID- 8439928 TI - Improving the treatment of out-of-hospital cardiac arrest. PMID- 8439929 TI - Avoidable injuries. PMID- 8439930 TI - Controversial computer system. PMID- 8439931 TI - Aerosol therapy in Canada: what are the standards? PMID- 8439932 TI - Why are there so many myths about AIDS? PMID- 8439933 TI - Implementing practice guidelines. PMID- 8439934 TI - HIV antibody testing in children. Infectious Diseases and Immunization Committee, Canadian Paediatric Society. PMID- 8439935 TI - Low-birth-weight symposium: summary of proceedings. PMID- 8439936 TI - Women in pediatrics: the experience in Quebec. AB - OBJECTIVES: To compare the practice patterns of female pediatricians in Quebec with those of their male counterparts and to identify specific factors influencing these practice patterns. DESIGN: Matched cohort questionnaire survey. SETTING: Primary, secondary and tertiary care pediatric practices in Quebec. PARTICIPANTS: All 146 female pediatricians and 133 of the 298 male pediatricians, matched for age as well as type and site of practice; 119 (82%) of the female and 115 (86%) of the male pediatricians responded. MAIN OUTCOME MEASURES: Demographic and family data as well as detailed information about the practice profile. RESULTS: The two groups were comparable regarding demographic data, professional work and patient care. Compared with the male respondents, the female pediatricians were younger and saw more outpatients. The mean number of hours worked per week, excluding on-call duty, was 40.5 (standard deviation [SD] 12.4) for the women and 48.9 (SD 12.0) for the men (p < 0.001). The female pediatricians were more likely than their male counterparts to have spouses who were also physicians (40%) or in another profession (45%). The female pediatricians without children worked significantly fewer hours than the male pediatricians with or without children (p < 0.001). Children (p = 0.006), but not the number of children (p = 0.452), had a significant effect on the number of hours worked by the female pediatricians. CONCLUSION: The duality of the role of female physicians as mothers and professional caregivers must be considered during workload evaluations. If the same style of practice and the increase in the proportion of female pediatricians continue, about 20% more pediatricians will be needed in 10 years to accomplish the same workload. PMID- 8439938 TI - Free AIDS pamphlets aimed at parents and women. PMID- 8439937 TI - Drowning deaths in people with epilepsy. AB - OBJECTIVE: To determine the demographic characteristics and risk factors associated with death from drowning among people with epilepsy. DESIGN: Retrospective review of medical examiner's investigations into deaths from drowning from Jan. 1, 1981, to Dec. 31, 1990. SETTING: Alberta. MEASURES: Personal data, medical history, circumstances surrounding the death, autopsy findings and results of postmortem toxicologic analyses. RESULTS: Of 482 deaths from drowning in Alberta during the study period, 25 (5%) were considered by the medical examiner's office to be directly related to seizures. Fifteen (60%) of the 25 deaths occurred while the person was taking a bath, unsupervised. Only one person (4%) died while taking a shower. The remaining deaths occurred on a river or lake (16%), in a private pool (8%), in a public pool (8%) and in a jacuzzi (4%). Two people fell out of moving boats while having a seizure; neither had been wearing a personal flotation device. Nineteen (83%) of 23 people who had been receiving anticonvulsant drug therapy had undetectable or subtherapeutic levels of one or more of the drugs at autopsy. Ethanol was not a factor in any of the deaths. CONCLUSIONS: Seizure-related drownings represent a small but potentially preventable proportion of all drownings. Enhanced seizure control and compliance with anticonvulsant drug therapy may prevent some of these deaths. In addition, all people with epilepsy, regardless of the level of control of their condition, should be encouraged to take showers while sitting instead of baths. The presence of people in the same house who are not directly supervising the person in the bathroom does not protect against drowning. Personal flotation devices should be worn at all times during boating activities. PMID- 8439939 TI - Hospital foundations raise large amounts of money, but also raise some troublesome issues. PMID- 8439940 TI - AIDS: the fictions, the facts. PMID- 8439941 TI - Medicolegal nightmare: a tragic case, a needless trial. PMID- 8439942 TI - "My worst fantasy is that the therapist-patient abuse will sink psychiatry as a profession": MD. PMID- 8439943 TI - Manitoba workshop provides insight into sexual abuse by physicians. PMID- 8439944 TI - Self-help movement experiencing rapid growth in Canada. PMID- 8439945 TI - Nazi medicine: "the perversion of the noblest profession". PMID- 8439946 TI - Genotype and phenotype of glutathione S-transferase class mu isoenzymes mu and psi in lung cancer patients and controls. AB - Glutathione S-transferase class mu (GSTM1) is known to detoxify certain carcinogens or their activated metabolites. In a previous study using phenotyping methods, individuals genetically devoid of this enzyme activity were significantly overrepresented among lung cancer patients compared to controls, suggesting that this trait is a risk factor for lung cancer. Here, GST class mu status has been determined both pheno- and genotypically, i.e., (a) by ex vivo measurement of trans-stilbene oxide conjugation in lymphocytes, (b) by GSTM1 quantification in blood using an immunoassay, and (c) by the application of polymerase chain reaction to genomic DNA with characterization of an inactivating mutation responsible for the null allele and a G/C single base allelic variance corresponding to the polymorphism of GSTM1 isoenzymes mu and psi, respectively. One hundred seventeen lung cancer patients and 155 control patients were studied. The two groups were of German origin and were similar with respect to age, sex, smoking history, and catchment area. In about 97% of cases, the three methods of assigning activity type of GSTM1 gave corresponding results. By genotype, 55 of 117 lung cancer patients (47.0%) and 73 of 155 control patients (47.1%) were GSTM1 active. The control group was confirmed by analysis of GSTM1 genotype in 200 further, independently studied reference patients; 101 of them were GSTM1 active (50.5%). Thus, the hypothesis of heritable GSTM1 deficiency as a host factor predisposing to lung cancer proved inappropriate. Detailed analysis of subgroups with respect to smoking habits, age, and sex failed to reveal an impact of GST class mu genotype on lung cancer risk. Among the total of 272 patients studied, 36 individuals carried at least one psi allele; however, no unexpected frequency distribution was observed. PMID- 8439947 TI - Absence of synergistic effects on tumor promotion in CD-1 mouse skin by simultaneous applications of two different types of tumor promoters, okadaic acid and teleocidin. AB - Okadaic acid, a specific inhibitor of protein phosphatases 1 and 2A, and teleocidin, an activator of protein kinase C, are both potent tumor promoters on mouse skin. The effects of simultaneous treatment of the two different types of tumor promoters on tumor promotion as well as on their biochemical activities were studied. Three independent experiments with different doses of tumor promoters revealed that simultaneous repeated applications of okadaic acid and teleocidin did not induce any synergistic or additive effects on tumor promotion in mouse skin initiated with 7,12-dimethylbenz(a)anthracene (DMBA). In Experiment 1, the group treated with a single application of DMBA, followed by repeated applications of 1.0 micrograms (1.2 nmol) okadaic acid and 2.5 micrograms (5.7 nmol) teleocidin, resulted in 64.3% tumor-bearing mice at week 20. But the groups treated with DMBA plus okadaic acid or DMBA plus teleocidin gave 73.3% and 71.4%, respectively. The biochemical activities were studied by means of induction of ornithine decarboxylase in mouse skin and protein phosphorylation in the cells. Simultaneous application of okadaic acid at three different doses with teleocidin did not induce ornithine decarboxylase activity synergistically or additively. Phosphorylation of proteins, cytokeratins, or heat shock protein 27 was not synergistically increased in human keratinocytes treated with okadaic acid and teleocidin, although the cotreatment in a cell-free system synergistically increased protein phosphorylation. Thus, the absence of synergistic effects on tumor promotion in mouse skin was also confirmed in two systems, induction of ornithine decarboxylase in mouse skin and protein phosphorylation in human keratinocytes. The effect of cotreatment of okadaic acid and teleocidin is discussed at the molecular level. PMID- 8439948 TI - Sulfotransferase-mediated activation of 4-hydroxy- and 3,4-dihydroxy-3,4 dihydrocyclopenta[c,d]pyrene, major metabolites of cyclopenta[c,d]pyrene. AB - Cyclopenta[c,d]pyrene, a ubiquitous environmental and occupational pollutant, has been reported to be metabolically activated through epoxidation at the 3,4 double bond in the cyclopenta ring to produce an electrophilic and mutagenic cyclopenta[c,d]pyrene-3,4-epoxide. 4-Hydroxy-3,4-dihydrocyclopenta[c,d]-pyrene (4 HDCPP) and 3,4-dihydroxy-3,4-dihydrocyclopenta[c,d]pyrene (3,4-DHDCPP) are known to be major metabolites of cyclopenta[c,d]pyrene, which appear to be derived from cyclopenta[c,d]pyrene-3,4-epoxide. The present study was undertaken to determine whether 4-HDCPP or 3,4-DHDCPP can be further activated via the formation of reactive benzylic sulfuric acid ester metabolites. Thus, when 4-HDCPP or 3,4 DHDCPP was incubated with calf thymus DNA in the presence of rodent liver cytosol and the sulfo group donor, 3'-phosphoadenosine-5'-phosphosulfate, a significant covalent DNA binding was observed. This cytosol- and 3'-phosphadenosine-5' phosphosulfate-dependent DNA binding was inhibited by 2,6-dichloro-4-nitrophenol and dehydroepiandrosterone, suggesting the involvement of both phenol and hydroxysteroid sulfotransferases in the activation of 4-HDCPP and 3,4-DHDCPP. A gender difference was observed for the hepatic cytosolic sulfotransferase activity for 4-HDCPP in rats (i.e., male > female). Of the two isomers of 3,4 DHDCPP, the trans-diol produced DNA adducts to a much greater extent than did the cis counterpart by sulfotransferase. 4-HDCPP and 3,4-DHDCPP were also mutagenic toward bacteria in the presence of hepatic cytosol and 3'-phosphadenosine-5' phosphosulfate. The chemically synthesized sulfuric acid ester 4-sulfooxy-3,4 DCPP was directly mutagenic without any activation system. The data from this study suggest that sulfotransferase plays an important role in the activation of those secondary benzylic hydroxyl metabolites derived from cyclopenta[c,d]pyrene 3,4-epoxide and, possibly, from epoxides of other aromatic hydrocarbons. PMID- 8439949 TI - Benzene and its phenolic metabolites produce oxidative DNA damage in HL60 cells in vitro and in the bone marrow in vivo. AB - Benzene, an important industrial chemical, is myelotoxic and leukemogenic in humans. It is metabolized by cytochrome P450 2E1 to various phenolic metabolites which accumulate in the bone marrow. Bone marrow contains high levels of myeloperoxidase which can catalyze the further metabolism of the phenolic metabolites to reactive free radical species. Redox cycling of these free radical species produces active oxygen. This active oxygen may damage cellular DNA (known as oxidative DNA damage) and induce genotoxic effects. Here we report the induction of oxidative DNA damage by benzene and its phenolic metabolites in HL60 cells in vitro and in the bone marrow of C57BL/6 x C3H F1 mice in vivo utilizing 8-hydroxy-2'-deoxyguanosine as a marker. HL60 cells (a human leukemia cell line) contain high levels of myeloperoxidase and were used as an in vitro model system. Exposure of these cells to phenol, hydroquinone, and 1,2,4-benzenetriol resulted in an increased level of oxidative DNA damage. An increase in oxidative DNA damage was also observed in the mouse bone marrow in vivo 1 h after benzene administration. A dose of 200 mg/kg benzene produced a 5-fold increase in the 8 hydroxydeoxyguanosine level. Combinations of phenol, catechol, and hydroquinone also resulted in significant increases in steady state levels of oxidative DNA damage in the mouse bone marrow but were not effective when administered individually. Administration of 1,2,4-benzenetriol alone did, however, result in a significant increase in oxidative DNA damage. This represents the first direct demonstration of active oxygen production by benzene and its phenolic metabolites in vivo. The conversion of benzene to phenolic metabolites and the subsequent production of oxidative DNA damage may therefore play a role in the benzene induced genotoxicity, myelotoxicity, and leukemia. PMID- 8439950 TI - Pediatric phase I trial and pharmacokinetic study of topotecan administered as a 24-hour continuous infusion. AB - Topotecan, a water-soluble semisynthetic analogue of camptothecin, is the first topoisomerase I inhibitor to undergo evaluation in pediatric patients with refractory malignancies. A phase I and pharmacokinetic study was performed to determine the maximum tolerated dose (MTD) and dose-limiting toxicities, the incidence and severity of other toxicities, and the pharmacokinetics of topotecan in children. Twenty-nine patients received 42 courses of i.v. topotecan administered as a 24-h continuous infusion every 21 days at doses ranging from 2.0 to 7.5 mg/m2. Dose-related hematological toxicity was the dose-limiting toxicity. Leukopenia, neutropenia, and thrombocytopenia occurred sporadically at the 3.0- to 5.5-mg/m2 dose levels, but at 7.5 mg/m2 4 of 5 patients experienced dose-limiting thrombocytopenia (grade 4) and 2 of 5 had dose-limiting neutropenia (grade 4). No other dose-limiting toxicities were observed. Nausea and vomiting were mild and occurred in < 20 and 10% of patients, respectively. Grade 2 hematuria occurred in one patient. No objective responses were observed. Pharmacokinetic studies revealed a linear relationship between the steady-state topotecan concentration and dose. The mean steady-state concentration at the MTD was 18.2 +/- 3.7 nmol/liter and the total body clearance was 28.3 +/- 6.5 liters/h/m2. Elimination was biexponential with a t1/2 alpha of 14.4 +/- 1.8 min and a t1/2 beta of 2.9 +/- 1.1 h. The recommended starting dose for phase II pediatric trials is 5.5 mg/m2. Although this dose exceeds the MTD identified in heavily pretreated adult patients receiving topotecan on the same schedule, it is less than the MTD for minimally pretreated adult patients. Therefore, dose escalation to 7.5 mg/m2 in phase II pediatric trials should be considered for patients who tolerate treatment well at the 5.5-mg/m2 dose. PMID- 8439951 TI - Clinical observations on adoptive immunotherapy with vaccine-primed T-lymphocytes secondarily sensitized to tumor in vitro. AB - The adoptive immunotherapy of human malignancy requires reliable methods to sensitize and expand patients' T-cells reactive to autologous tumors. In animal studies, we have generated therapeutic effector cells against a poorly immunogenic tumor by a two-step procedure: vaccination of the host followed by the secondary stimulation of vaccine-primed lymph node (LN) cells by in vitro sensitization (IVS) with tumor in the presence of interleukin 2 (IL-2). Based on these observations, we performed a clinical trial in patients with advanced cancer to evaluate the antitumor efficacy of vaccine-primed LN cells which were similarly activated in vitro. Patients were vaccinated with irradiated autologous tumor admixed with Bacillus Calmette-Guerin and had draining LN excised 10 days later for IVS culture. During IVS culture, LN cells expanded up to 14-fold (average of 8.4-fold). A mean of 6.7 x 10(9) cells was infused in ten patients (seven melanoma, three renal cell cancer) along with the concomitant i.v. administration of IL-2 (180,000 IU/kg every 8 h for 5 days). Phenotype analysis of IVS-LN cells revealed 78 +/- 4% CD3+ T-cells which were predominantly CD4+ (67 +/- 5%) with expression of HLA-DR and IL-2 receptor. IVS-LN cells displayed relative specificity of autologous tumor lysis in four of ten cases compared to zero of seven IVS-peripheral blood lymphocytes derived from the same patients as measured by the 51Cr release assay. One mo after therapy, seven of nine patients treated with IVS-LN cells and IL-2 developed delayed-type hypersensitivity reactivity to autologous tumor compared to zero of nine patients treated with tumor vaccination and IL-2 only (P < 0.002). These observations suggest that antitumor reactivity was passively transferred with the IVS-LN cells. Major toxic side effects including fever, hepatic dysfunction, and weight gain associated with the capillary leak syndrome were associated with exogenous IL-2 administration. Tumor vaccination and cell transfer were well tolerated without significant complications. Of the ten patients treated with IVS-LN cells and IL 2, there were one partial and one minor response, and one patient has had stable disease for 27+ mo. There was no evidence of tumor response in ten patients treated with tumor vaccination and IL-2 only. Further clinical studies evaluating the antitumor reactivity of vaccine-primed LN cells are warranted. PMID- 8439952 TI - Genetic susceptibility for C19 androgen induction of ovarian granulosa cell tumorigenesis in SWXJ strains of mice. AB - Susceptibility to pubertal onset, malignant granulosa cell (GC) tumors of the ovary is inherited in SWR/Bm and certain SWR-related SWXJ recombinant inbred strains of mice. In some SWXJ strains, GC tumors occur spontaneously (spontaneous strains), and in others GC tumors can only be induced by treatment with dehydroepiandrosterone (DHEA-dependent strains). A gene controlling susceptibility to both spontaneous and DHEA-induced GC tumorigenesis, Gct, has been assigned to Chromosome 4. Additional research on the role of steroids in GC tumorigenesis has revealed a second gene controlling response to C19 androgenic steroids. Spontaneous strains showed increased tumor frequency after treatment with testosterone (T), whereas DHEA-dependent strains showed no GC tumors following T treatment. Within treatment groups, serum steroid data from DHEA, T, and control treated mice showed no consistent differences between spontaneous and DHEA-dependent strains with respect to progesterone, DHEA, androstenedione, dihydrotestosterone, T, estrone, or estradiol. Thus, observed differences in GC tumor responsiveness to exogenous steroids were not due to different patterns of steroid metabolism among spontaneous and DHEA-dependent strains. Further studies on the range of effective C19 steroids were conducted using one spontaneous and one DHEA-dependent strain. The spontaneous strain showed increased GC tumor frequency in response to dihydrotestosterone and androsterone treatment, whereas the DHEA-dependent strain showed no response. This result suggests that spontaneous strains may be sensitive to a broad range of C19 steroids. To determine whether genetic differences in endogenous steroid levels have a role in spontaneous GC tumorigenesis, serum steroid levels were measured in SWR/Bm and SJL/Bm progenitor strains during the developmental period of risk between 22 and 38 days of age. With the exception of transiently increased DHEA at 22 days, there were no consistent differences in steroid levels analyzed. Thus, serum steroid profiles were not reliably prognostic for GC tumorigenesis. In conclusion, GC tumor induction in response to T treatment has co-segregated with susceptibility to spontaneous GC tumors in the SWXJ recombinant inbred strains. Thus, the second gene in our ovarian granulosa cell tumor model regulates responsiveness to T. We propose to name this gene spontaneous ovarian tumorigenesis (Sot), with alleles for susceptibility (s) carried by spontaneous strains and resistance (r) carried by DHEA-dependent strains. PMID- 8439953 TI - Synergistic antitumor activity of cisplatin and interleukin 1 in sensitive and resistant solid tumors. AB - The antitumor activity of cis-diamminedichloroplatinum(II) (cP) and human recombinant interleukin-1 alpha (IL-1 alpha) was studied in RIF-1 and SC VII solid tumor models and in a cP-resistant subline of RIF-1 designated RIF-R1cP. In RIF-1 tumors, clonogenic cell survival after cP plus IL-1 alpha combinations was highly schedule and IL-1 alpha dose dependent. More than additive clonogenic cell kill was seen when cP was given 6 h before, but not 8 h before or at 2-6 h after IL-1 alpha. Time course studies indicated that maximal clonogenic cell killing was achieved within 4-6 h after the cP plus IL-1 alpha combination, with little or no recovery for up to 24 h. In vivo dose-response studies indicated that cP plus IL-1 alpha combinations induced more clonogenic cell kill than cP alone in all three tumor models, and analysis by the median effect principle indicated highly synergistic antitumor activity. Dexamethasone but not indomethacin inhibited the synergistic interaction. IL-1 alpha had no effect on the cytotoxicity of cP in SCC VII cells in vitro, and neither in vitro hypoxia nor in vivo ischemia, induced by clamping tumor blood supply, significantly affected cP clonogenic cell killing. Increased clonogenic cell killing was seen, however, after removal of the clamp, implicating reperfusion events, such as oxyradical stress, as a potential mechanism for increased cP cytotoxicity in SCC VII solid tumors. The data from our model systems provide a rationale for additional work to define the mechanisms of the synergistic antitumor activity of the cP plus IL 1 alpha combination and indicate that IL-1 alpha might be a useful adjunct to increase the clinical efficacy of cP-containing strategies for both sensitive and cP-resistant cancers. PMID- 8439954 TI - Inhibition of growth of prostatic cancer cell lines by peptide analogues of insulin-like growth factor 1. AB - We have investigated three prostatic cancer cell lines, PC-3, DU-145, and LNCa.FGC, and found that all three cell lines can grow in serum-free medium without the addition of exogenous growth factors. All three cell lines produce substantial amounts of insulin-like growth factor 1 (IGF-1) that is secreted in the medium and they all display constitutively autophosphorylated IGF-1 receptors; two of the cell lines overexpress IGF-1 receptor RNA. The growth of all three cell lines is inhibited by an antisense oligodeoxynucleotide to IGF-1 receptor RNA or by peptide analogues of IGF-1 that compete with IGF-1 binding to its receptor. Our results indicate that these three cell lines grow by an autocrine loop in which the overproduced IGF-1 activates its receptor. Interference with the activation of the receptor leads to cessation of growth. PMID- 8439955 TI - Alpha 1-interferon gene transfer into metastatic Friend leukemia cells abrogated tumorigenicity in immunocompetent mice: antitumor therapy by means of interferon producing cells. AB - Highly metastatic alpha/beta-interferon (IFN-alpha/beta)-resistant Friend leukemia cells (FLC) were transfected with a retroviral vector (pLTneoL-5) containing the mouse IFN-alpha 1 gene. Transfected clones were isolated and tested for their capacity to secrete IFN-alpha 1 and their tumorigenicity when injected s.c. into immunocompetent syngeneic DBA/2 mice. Almost all FLC clones producing IFN in the range of 16-512 units/ml failed to grow when injected s.c. or i.p. into normal mice, whereas control FLC (transfected with a vector without the IFN gene) exhibited the highly malignant phenotype of the original FLC. High levels of IFN were detected in peritoneal fluid, tumor extracts, and sera of mice given injections of IFN-producing cells. Injection of mice with antibodies to IFN alpha/beta resulted in the development of tumor ascites in mice transplanted i.p. with IFN-producing FLC. In contrast to the tumor rejection observed in immunocompetent mice, IFN-producing FLC were highly tumorigenic when transplanted into immunosuppressed nude mice. Mice given injections of IFN-producing FLC developed a long-lasting tumor-specific immune resistance to subsequent injection with highly metastatic FLC. Simultaneous s.c. injection of both metastatic FLC (approximately 10(3) 50% lethal doses) and IFN-producing cells resulted in potent inhibition of the tumor growth, with a survival rate of approximately 50% for injected mice. Contralateral injection (s.c.) of IFN-producing FLC into mice with established metastatic tumors produced a marked inhibition of tumor growth, with a survival rate of 10% for injected mice. These results indicate that: (a) the genetic modification of highly metastatic FLC by means of transfer of the IFN alpha 1 gene results in potent tumor cell rejection, which is mediated by an IFN induced host immune response; (b) injections of IFN-producing tumor cells are effective in inhibiting tumor growth in mice with established metastatic tumors. These data suggest that tumor cells transfected with the IFN-alpha gene might be used as an effective therapy for the treatment of certain human metastatic tumors, provided that suitable strategies are defined to prevent growth of the cytokine-producing cells. PMID- 8439956 TI - Protection against experimental cerebral metastases of murine melanoma B16 by active immunization. AB - Melanoma patients often develop brain metastases despite effective systemic immunotherapy against melanoma. We have attempted to establish a mouse model to develop strategies to combat this problem. Immunization of C57BL/6 (H-2b) mice with a combination of the syngeneic G3.12/BM2 melanoma (a B16 subclone) and the allogeneic Cloudman-S91 melanoma was effective in preventing the growth of 10,000 viable, s.c. injected G3.12 cells in 93% of the mice. Irradiated whole tumor cells pretreated with gamma-interferon for 2 days were most effective. A nonspecific adjuvant (DETOX) was injected routinely together with the tumor cells. Active immunization with 2 different doses of irradiated melanoma cells (1 x 10(5) or 2.5 x 10(6) cells/injection x 5 injections) protected against intracerebral challenge with 200 live G3.12 cells in 69% of the mice. This challenge caused the death of all control mice within 30 days. T-cell-mediated, tumor-specific cytotoxicity against G3.12 melanoma was demonstrated in the spleen of immunized mice. Histological observations in the brain, 80 days after tumor challenge, indicated complete eradication of the melanoma, but although CD4+ and CD8+ T-cells and macrophages were present, their number was low. Gliosis was present in both immunized and control animals. Thus, in this murine melanoma model syngeneic mice were protected from death by s.c. and intracerebrally inoculated tumor cells if pretreated with a sufficient number of irradiated syngeneic and allogeneic melanoma cells and an immunological adjuvant. Whether this regimen can treat established tumors of the brain, alone or in combination, is uncertain. Yet its success suggests that the "blood-brain barrier" impeding immunity to tumors may not be absolute. PMID- 8439957 TI - AgSK1, a novel carcinoma associated antigen. AB - An IgM human monoclonal antibody (HuMAb) SK1 was generated from mesenteric nodal lymphocytes of a colon cancer patient that were fused with a human B lymphoblastoid cell line SHFP-1. The reactivities of HuMAb SK1 to various human cell lines were screened by cell enzyme linked immunosorbent assay and immunocytochemical staining. The HuMAb SK1 reacted strongly with all 11 human carcinoma cell lines that were tested and had no detectable binding with noncarcinoma cell lines of the following origins: fibroblast; fetal lung; melanoma; soft tissue sarcoma; neuroblastoma; and glioblastoma. Carcinoma preferred reactivity of HuMAb SK1 was further confirmed by immunoperoxidase staining of a large number of frozen tissues, both malignant and benign. The antigen SK1 (AgSK1) in human carcinoma detected by immunoperoxidase staining was also identified biochemically as a sialoglycoprotein that migrated at M(r) 42,000 with an isoelectric point (pI) of approximately 5.9. A preferential staining by HuMAb SK1 was seen among colorectal, gastric, pancreatic, and lung cancers. Competitive inhibition study in solid-phase immunoassay suggested that the HuMAb SK1 did not cross-react with other antibodies specific for CEA, CA 19-9, and TAG 72. The AgSK1 appears to be a novel carcinoma associated antigen which may be a useful tumor marker in cancer diagnosis and treatment. PMID- 8439958 TI - Differential effect of ionizing radiation on the expression of cyclin A and cyclin B in HeLa cells. AB - Ionizing radiation induces a G2 delay in eukaryotic cells. Since mitotic cyclins are required to trigger the transition from G2 into and through mitosis, we chose to investigate their expression after irradiation in HeLa cells. In normally cycling HeLa cells, both cyclin A and B mRNA and protein levels rise dramatically in G2/M and rapidly fall coincident with the completion of mitosis. The rise of cyclin A mRNA at the S/G2 boundary slightly precedes that of cyclin B mRNA. Although the peaks of expression of each of these molecules overlap, cyclin A mRNA and protein diminish before cyclin B. After irradiation in S, cyclin A mRNA and protein levels rose with the same kinetics as in the controls, but ultimately exceeded the levels seen in the control population. Cyclin A mRNA and protein levels remained high throughout the G2 delay induced by irradiation. In contrast, cyclin B mRNA and protein levels did not rise as the irradiated cells entered G2/M. Only later, before the irradiated cells exited from G2/M, did levels of cyclin B reach the levels seen in the unirradiated controls. The decreased amount of cyclin B mRNA and protein was inversely proportional to the dose of radiation. These data indicate that irradiation that results in a G2 delay appears to block cells at a point after production of cyclin A but before cyclin B can be fully expressed and that cells do not exit from the delay until cyclin B is again expressed. Thus, cyclin A and cyclin B expression respond differentially to radiation, with cyclin A rising at the same time as the control and to even higher levels than that seen in the controls, whereas cyclin B shows a temporal delay in expression. PMID- 8439959 TI - Dimethyl sulfoxide inhibits the binding of granulocyte/macrophage colony stimulating factor and insulin to their receptors on human leukemia cells. AB - Numerous agents can induce the terminal differentiation of leukemia cells in vitro, and this action has been found to be of therapeutic value in the treatment of acute promyelocytic leukemia. The proximal site of action of the prototypical chemical inducer of differentiation, dimethyl sulfoxide (DMSO), is not known. In this study, DMSO was found to rapidly cause a 45% to 85% reduction in the specific binding of the growth factors granulocyte/macrophage colony-stimulating factor and insulin to their respective cell surface receptors on HL-60 human acute promyelocytic leukemia cells. Significant inhibition of binding was first observed after 30 min of DMSO treatment, occurred at both 4 degrees C and 37 degrees C, and was due to a DMSO-induced decrease in apparent receptor affinity, with little change in receptor number. A similar inhibition of insulin binding was seen with a second inducer of differentiation, hexamethylene bisacetamide. Kinetic studies demonstrated that DMSO enhanced the rate of insulin dissociation from its receptor. The inhibition of insulin binding by DMSO was also observed in a cell-free extract, suggesting that the effect was not a cell-mediated response to DMSO treatment. DMSO blocked the insulin-induced stimulation of protein tyrosine phosphorylation. These studies suggest that one action of DMSO may be the disruption of the structure and/or organization of cell surface receptors that regulate growth and differentiation. PMID- 8439960 TI - Mutagenic processing of ethylation damage in mammalian cells: the use of methoxyamine to study apurinic/apyrimidinic site-induced mutagenesis. AB - The aldehyde reagent methoxyamine is able to interact with apurinic/apyrimidinic sites formed in vivo within cells and displays both an anti-cytotoxic and an antimutagenic activity on N-ethyl-N'-nitro-N-nitrosoguanidine-induced DNA damage in Chinese hamster ovary cells. To clarify the underlying mechanism we have examined the mutational spectra induced by N-ethyl-N'-nitro-N-nitrosoguanidine alone and in the presence of methoxyamine in the hypoxanthine-guanine phosphoribosyltransferase gene of Chinese hamster ovary cells. In both cases all mutations were base pair substitutions, and their distribution among various classes did not differ significantly. Almost 60% were transitions, predominantly GC to AT, and the remaining 40% were transversions, mainly at AT base pairs. The analysis of the proportion of the different types of mutations showed that in the presence of methoxyamine, GC to AT transitions decreased by a factor of 1.8, and AT to CG transversions were reduced by a factor of 13. These data indicate that in mammalian cells the fixation of ethylation damage into mutations occurs by both (a) direct mutagenesis likely driven by O6-ethylguanine adducts and to a minor extent by O4-ethylthymine and (b) apurinic/apyrimidinic site-mediated mutagenesis. These apurinic/apyrimidinic sites are formed during the processing of ethylation at critical sites and are likely to involve O6-ethylguanine and O2 ethylthymine adducts. PMID- 8439961 TI - Induced megakaryocytic maturation of the human leukemia cell line UT-7 results in down-modulation of erythropoietin receptor gene expression. AB - Erythropoietin (Epo) affects not only erythrocyte production but, in vitro, also promotes megakaryocyte maturation. However, the mechanism of action of Epo on megakaryocytic development remains to be determined. Recently, we reported the establishment of a human Epo-dependent megakaryoblastic leukemic cell line UT-7. Exposure of UT-7 to the tumor promoter, phorbol myristate acetate (PMA), resulted in the appearance of mature megakaryocytic properties, including the expression of platelet factor 4 and beta-thromboglobulin. With exposure to PMA, however, UT 7 cells lost their responsiveness to Epo and Scatchard analysis showed an 85% decrease in the number of Epo receptors after 24 h. While the number of binding sites declined, the affinity of Epo binding was unchanged. Associated with the decline in the number of Epo receptors was a profound decrease (> 95%) in the level of Epo receptor (Epo-R) mRNA. To determine the level of regulation of the Epo-R gene, its rate of transcription was measured by nuclear run-off assay in untreated cells and in cells exposed to PMA for 6, 12, and 24 h. The rate of transcription was nearly identical at all time points in control and PMA-treated cells. Stability of Epo-R mRNA also was measured in the presence of actinomycin D, an inhibitor of transcription. The half-life of Epo-R mRNA in untreated and PMA-treated cells was 90 and 30 min, respectively. These results indicate that the down-modulation of the expression of the Epo-R gene is mainly caused by increased instability of mature mRNA of Epo-R. Posttranscriptional regulation may be an important mechanism in the regulation of hematopoietic growth factor receptor genes and one of the mechanisms by which lineage restriction is achieved. PMID- 8439962 TI - Distinct pattern of p53 mutations in bladder cancer: relationship to tobacco usage. AB - A distinct mutational spectrum for the p53 tumor suppressor gene in bladder carcinomas was established in patients with known exposures to cigarette smoke. Single-strand conformational polymorphism analysis of exons 5 through 8 of the p53 gene showed inactivating mutations in 16 of 40 (40%) bladder tumors from smokers and 13 of 40 (33%) tumors from lifetime nonsmokers. Overall, 13 of the 50 (26%) total point mutations discovered in this and previous work were G:C-->C:G transversions, a relatively rare mutational type in human tumors. In six tumors, identical AGA (Arg)-->ACA (Thr) point mutations at codon 280 were observed, suggesting a mutational hotspot in these tumors. Comparison of the mutational spectra from smokers and nonsmokers revealed no obvious differences in the types or positions of inactivating mutations; however, 5 of 15 tumors containing point mutations from cigarette smokers had double mutations, four of which were tandem mutations on the same allele. No double mutations were found in tumors from nonsmoking patients. None of the mutations in smokers were G:C-->T:A transversions, which would be anticipated for exposure to the suspected cigarette smoke carcinogen 4-aminobiphenyl. The results suggest that, although cigarette smoke exposure may not significantly alter the kinds of mutations sustained in the p53 gene, it may act to increase the extent of DNA damage per mutagenic event. PMID- 8439963 TI - Evidence for the presence of two tumor suppressor genes on chromosome 8p for colorectal carcinoma. AB - We have examined loss of heterozygosity on the short arm of chromosome 8 in 133 colorectal carcinomas, using 20 restriction fragment length polymorphism markers. Loss of heterozygosity was observed in 58 (44%) of 131 tumors that were informative with at least one locus. Among these 58, 32 revealed a partial or interstitial deletion of chromosome 8p. Detailed deletion mapping of chromosome 8p in these tumors identified two distinct, commonly deleted regions. One was located between markers C18-266 and pSVL-LPL at 8p23.2-8p22, and the other between CI8-319 and CI8-494 at 8p21.3-8p11.22. The genetic lengths of these two intervals were estimated to be 28 and 18 cM, respectively. The results suggest that at least two tumor suppressor genes associated with colorectal carcinomas are present on chromosome 8p. Correlation of loss of heterozygosity on 8p to the clinicopathological stage was also detected, suggesting that inactivation of a tumor suppressor gene(s) on 8p plays a role in progression of colorectal carcinomas. PMID- 8439964 TI - Purification and characterization of a novel cytotoxic protein from transformed fibroblasts. AB - The mechanism by which cancer cells overwhelm normal parenchymal cells during cancer invasion remains obscure. In this article, we describe the purification of a potent cytotoxic protein from plasma membranes of ras oncogene transformed fibroblasts. Tumor cytotoxic protein was purified from detergent extracted tumor membranes by anion exchange and gel filtration chromatography. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate indicated that the hemolytic fractions contained a single protein with an apparent molecular weight of 62,000. A higher concentration of tumor cytotoxic protein was required to lyse fibroblasts as compared to RBC. Based on plasma membrane localization, immunological identity, and biological characteristics, tumor cytotoxic protein is a novel cytolysin which is capable of killing normal cells during cancer invasion. PMID- 8439965 TI - Nude mouse metastatic models of human stomach cancer constructed using orthotopic implantation of histologically intact tissue. AB - Nude mice have been used to develop s.c. growing human stomach tumors, but these rarely metastasize. Recently, I. J. Fidler and others have developed orthotopic implantation metastatic models using cell suspensions which are inoculated into the corresponding organ of nude mice from which the tumor cells were originally derived in the human. However, recent work has indicated that disaggregated cell suspensions may not always express their full metastatic potential. In this light, we have recently developed an orthotopic implant model utilizing intact tissue such as that obtained directly from surgery. This approach has yielded high take rates and frequent metastases in colon cancer, bladder cancer, lung cancer, pancreatic cancer, and prostate cancer. We report here the application of this intact tissue orthotopic implant technique to stomach cancer resulting in the formation of metastases in 100% of the mice with extensive primary growth to the regional lymph nodes, liver, and lung. In contrast, when cell suspensions were used to inject stomach cancer cells at the same site, metastases occurred in only 6.7% of the mice with local tumor formation, emphasizing the importance of using intact tissue to allow full expression of metastatic potential. Injuring the serosa similar to that occurring in intact tissue transplantation did not increase the metastatic rate after orthotopic injection of cell suspensions of stomach tumor cells. This intact tissue orthotopic implantation model should allow development of new treatment modalities and further study of the biology of human stomach cancer. PMID- 8439966 TI - A rapid colorimetric in situ messenger RNA hybridization technique for analysis of epidermal growth factor receptor in paraffin-embedded surgical specimens of human colon carcinomas. AB - We have developed a rapid colorimetric in situ mRNA hybridization procedure to analyze epidermal growth factor receptor (EGF-R) transcripts in paraffin-embedded surgical specimens of human colon carcinomas. This technique is based on the use of 24-base oligonucleotide probes labeled with 6 biotin molecules at the 3' end. mRNA integrity was verified using a hyperbiotinylated 30-residue-long deoxythymidylate oligonucleotide probe, and the specificity of the reaction was confirmed by using labeled EGF-R-specific sense and antisense probes. Avidin alkaline phosphatase detection and the capillary technology used in the Microprobe System allowed for completion of the procedure in under 5 h. The human A431 epidermoid carcinoma cells growing in culture and fixed with formalin as well as paraffin-embedded sections of this tumor growing s.c. in nude mice served as positive controls. In situ hybridization with antisense EGF-R oligonucleotide probes directly correlated with EGF-R mRNA and protein levels observed by Northern blot and immunohistochemistry, respectively. In situ hybridization of paraffin-embedded sections of primary human colon carcinoma and metastases from liver and lymph node revealed cell-specific staining with EGF-R antisense oligonucleotide probes that correlated directly with Northern blot and immunohistochemistry analyses. Since this rapid and sensitive in situ mRNA hybridization technique can be used in properly preserved paraffin-embedded tissue, it allows for retrospective analyses of human tumor specimens using archival material. PMID- 8439967 TI - Evidence for the involvement of a bis-diol-epoxide in the metabolic activation of dibenz[a,h]anthracene to DNA-binding species in mouse skin. AB - Dibenz[a,h]anthracene (DB[a,h]A) and its microsomal metabolites, trans-3,4 dihydro-3,4-dihydroxydibenz[a,h]anthracene (DBA-3,4-diol), trans,trans-3,4:8,9 tetrahydro-3,4:8,9-tetrahydroxydibenz[a,h]anth racene, trans,trans-3,4:10,11 tetrahydro-3,4:10,11-tetrahydroxydibenz[a,h] - anthracene (DBA-3,4,10,11-bis diol) and trans,trans-3,4:12,13-tetrahydro-3,4:12,13- tetrahydroxydibenz[a,h]anthracene were each applied topically to mouse skin and the epidermal DNA isolated 24 h later. 32P-postlabeling analysis of each of the DNA samples was performed. DNA from mice treated with DB[a,h]A produced an adduct map on TLC consisting of one major and three minor adduct spots. A similar pattern of spots was produced by DBA-3,4-diol. No detectable DNA adducts were produced by trans,trans-3,4:12,13-tetrahydro-3,4:12,13-tetrahydroxy- dibenz[a,h]anthracene, although a single, minor adduct spot was produced by trans,trans-3,4:8,9-tetrahydro-3,4:8,9-tetrahydroxydibenz[a,h]- anthracene. However, DBA-3,4,10,11-bis-diol was found to produce a major single adduct that comigrated on thin layer chromatography with the major adduct produced by both DB[a,h]A and DBA-3,4-diol. In addition, this adduct was present at a level 10 times higher than the corresponding adduct produced by treatment with the parent hydrocarbon. Coelution of the major adducts formed from DB[a,h]A and DBA-3,4-diol with that formed from DBA-3,4,10,11-bis-diol was also demonstrated on reverse phase high performance liquid chromatography. Thus, we propose that, in mouse skin, the major pathway of DB[a,h]A activation to DNA binding products is via a 3,4-diol to the 3,4,10,11-bis-diol and ultimately to a bis-diol-epoxide (potentially the 3,4,10,11-bis-dihydrodiol-1,2-oxide). PMID- 8439968 TI - Transfection of interleukin 2 gene into human melanoma cells augments cellular immune response. AB - A preclinical model was used to determine if transfection of the interleukin 2 (IL-2) gene into human melanoma cells would augment the response of autologous and allogeneic peripheral blood lymphocytes (PBLs) from melanoma patients. IL-2 gene was transfected into three human melanoma cell lines; secretion of IL-2 from stable transfected cells was confirmed by enzyme-linked immunosorbent assay. The PBL response to these melanoma cells was then examined in a mixed-lymphocyte tumor reaction using PBLs from eight melanoma patients. The PBL response to autologous (P < 0.01) or human leukocyte antigen A cross-reactive (P < 0.05) transfected melanoma cells was significantly higher than it was to nontransfected melanoma cells. These data suggest that IL-2 gene transfection may be an important strategic approach to enhancing specific immune responses induced by a polyvalent melanoma cell vaccine. PMID- 8439969 TI - Frequent c-Ki-ras oncogene activation in mucous cell hyperplasias of pancreas suffering from chronic inflammation. AB - In order to scrutinize the possible significance of (nonatypical) mucous cell hyperplasia of the pancreas to neoplasia, we analyzed these lesions in terms of c Ki-ras activation, which is known to be very frequent in pancreatic carcinomas. A total of 16 such mucous cell hyperplasias were collected from 10 pancreases resected for chronic pancreatitis. Tiny tissue fragments were taken from hematoxylin-stained sections by microdissection, and DNA analysis was carried out by the polymerase chain reaction amplification and oligonucleotide hybridization methods. Activating mutations of c-Ki-ras oncogene at codon 12 were detected in 10 of the 16 lesions (62.5%), a high rate as seen in carcinomas. The results indicated a clonal origin of cells comprising the mucous cell hyperplasia suggesting a neoplastic and/or precancerous nature. PMID- 8439970 TI - Turcot's syndrome of glioma and polyposis occurs in the absence of germ line mutations of exons 5 to 9 of the p53 gene. AB - The term "Turcot's syndrome" has been used to describe approximatively 55 patients with an association of colonic polyposis and primary neuroepithelial tumors of the central nervous system. The p53 tumor suppressor gene is a possible candidate underlying the syndrome because (a) mutations in the p53 gene are ubiquitous in human cancer, including colon carcinoma and gliomas, and (b) somatic or germ line mutations of the p53 tumor suppressor gene cause the Li Fraumeni syndrome, which is characterized by the association of breast and soft tissue tumors. We determined the DNA sequence of the conserved regions of the p53 gene (exons 5 to 9) in the tumor tissues and lymphocytes of two patients with glioma-polyposis and found that mutations did occur as independent tumor-specific alterations but did not involve the germ line of these patients, suggesting that p53 may play a role in progression but not initiation of the disease. PMID- 8439971 TI - In vitro and in vivo targeting of gene expression to melanoma cells. AB - Gene therapy protocols for cancer usually involve removal of tumor cells, culture in vitro to allow gene transfer, and subsequent reintroduction in vivo. Targeting therapeutic genes to tumor cells in situ requires an accuracy of gene delivery that currently is not possible with the use of existing techniques. To overcome these limitations we have used two promoters, which are preferentially active in melanocytic cells, to direct gene expression specifically to melanoma cells both in vitro and in vivo. Here we describe experiments showing that as little as 769 base pairs of the 5'-flanking regions of the tyrosinase, and 1.4 kilobase pair of the tyrosinase-related protein 1, genes are sufficient to direct expression of the beta-galactosidase gene to both human and murine melanoma cells and melanocytes, while not permitting expression in a range of other cell types in vitro. These promoters showed high levels of activity in 12 of 14 murine and human melanoma cell lines tested but showed only basal levels of activity, similar to that of a promoterless construct, in a range of 12 other cell types. Cell type specificity is maintained when the construct is delivered to cells either by physical means or by inclusion of the cell type-specific expression cassette into a retroviral vector. Direct injection of DNA, encoding the beta galactosidase gene expressed from either promoter, into established B16 melanomas or Colo 26 tumors in syngeneic mice resulted in extensive transduction of tumor cells in the B16 melanomas (approximately 10% of tumor cells expressing 10 days after DNA injection), whereas no blue-staining cells were seen in the Colo 26 tumors. The reporter gene was expressed in melanoma cells and in some normal melanocytes but not in other surrounding normal tissue. We propose that the combination of a tissue-specific promoter driving a therapeutic gene, with delivery of such a construct directly to sites of tumor growth in vivo, either by direct DNA injection or by retroviral infection, may provide significantly enhanced safety for gene therapy for solid tumors. PMID- 8439972 TI - Reversal of cytochrome P-4501A1 and P-450-EF expression in MCA-C3H/10T1/2 cell derived tumors as compared to cultured cells. AB - The 3-methylcholanthrene-transformed tumorigenic cell line, MCA-C3H/10T1/2 CL15 (MCA), expresses the novel benz(a)anthracene (BA)-inducible polycyclic aromatic hydrocarbon-metabolizing cytochrome P-450 (P-450-EF). The level of expression is comparable to that reported for the nontumorigenic C3H/10T1/2 CL8 (10T1/2) cells (Pottenger, L. H., Christou, M., and Jefcoate, C. R. Arch. Biochem. Biophys., 286: 488-497, 1991). Sarcomas (3-12 mm in diameter) generated in athymic "nude" mice by s.c. injection of MCA cells exhibited much lower 7,12 dimethylbenz(a)anthracene-metabolizing activities (5-15% of the levels in cultured cells), both constitutively and after in vivo treatment with BA. A sharp decrease in P-450-EF expression was observed both at the functional level (10- to 30-fold) (as determined by antibody inhibition studies) and at the apoprotein level (50- to > 100-fold) (as determined by Western immunoblots). However, in contrast to the BA-treated MCA cells in which P-450-EF comprises essentially the total spectrally detectable P-450 content (approximately 30 pmol/mg) with virtually undetectable cytochrome P-4501A1, tumors from these cells expressed substantial levels of P-4501A1 immunodetectable protein in response to BA treatment (approximately 0.5-3 pmol/mg). In these tumors, P-450-EF expression decreased to undetectable or barely detectable levels (< 0.2-0.5 pmol/mg). P 4501A1-expressing cells were localized in tumor sections immunocytochemically and were morphologically identical to other MCA cells, which formed the majority of the sarcoma. At the functional level, antibody inhibition studies and product ratios demonstrated that P-4501A1 accounted for only 40% of the total dimethylbenz(a)anthracene-metabolizing activity of BA-induced tumor microsomes, whereas the remaining activity was due to P-450-EF. This low catalytic activity for P-4501A1 (35-95 pmol/mg/h) indicated that the majority of BA-inducible P 4501A1 in the tumors (> 95%) was expressed as apoprotein. The contribution from P 450-EF was consistent with full expression of hemoprotein. Tumor size affected the total dimethylbenz(a)anthracene-metabolizing activities/mg microsomal protein (small tumors were 2- to 3-fold more active than large tumors) but had no effect on the ratio of activities dependent on, respectively, P-450-EF and P-4501A1 holoenzymes (1.5:1), thus suggesting controlled coexpression of these proteins. Reculturing of tumor-derived cells effected partial restoration of P-450-EF expression and eliminated the expression of P-4501A1, confirming a unique contribution from tumor environment to the regulation of these genes. Possible mechanisms for an environment-dependent concerted regulation of the P-4501A1 and P-450-EF genes are discussed. PMID- 8439973 TI - Specificity of bischloroethylnitrosourea-induced mutation in a Chinese hamster ovary cell line transformed to express human O6-alkylguanine-DNA alkyltransferase. AB - The human O6-alkylguanine-DNA alkyltransferase complementary DNA was transfected into the alkyltransferase-deficient Chinese hamster ovary cell line, D422, in an effort to dissect the underlying mechanisms of bischloroethylnitrosourea (BCNU) induced mutations. The alkyltransferase-transformed cell line exhibited 100-fold protection against BCNU-induced toxicity and an overall decrease in mutation frequency to 25% of that observed in the parental cell line at the hemizygous adenine phosphoribosyl transferase gene target. The frequency of the predominant mutation in the parental cell line, the G:C-->T:A transversion, was reduced from 16 x 10(-6) to 0.7 x 10(-6) in the O6-alkyltransferase-transformed cell line. Likewise, the G:C-->A:T transitions, the second most common BCNU-induced mutation in the parental cell line, was reduced in frequency from 5.2 x 10(-6) to 0.9 x 10(-6) in the alkyltransferase-transformed Chinese hamster ovary cells. These findings suggest that both the G:C-->T:A transversions and G:C-->A:T transitions were O6-alkylguanine-mediated mutations. In the alkyltransferase-transformed Chinese hamster ovary cell line, T:A-->G:C transversions, comprising 45% (23 of 51) of the recovered mutations, emerged as the most common base substitution. In summation, in the absence of alkyltransferase-dependent DNA repair, mutations resulting from O6-alkylation of guanine underlie both the cytotoxic and mutagenic activity of BCNU. In cells expressing high levels of alkyltransferase activity, the cytotoxic and mutagenic actions of BCNU are greatly reduced and mutations resulting from A:T base pair modifications appear to be the major genotoxic lesions induced by the drug. PMID- 8439974 TI - Interleukin-2 in cancer treatment: disappointing or (still) promising? A review. AB - The central question to discuss in this review is whether the results of interleukin-2 (IL-2) treatment are still disappointing or again promising. Although in the (recent) past application of high doses of systemically applied rIL-2 has led to some success, the overall results are not as one had hoped. Considering these poor results it seems clear that the application of high systemic doses rIL-2 was not a good choice. IL-2 has been used more or less as a chemotherapeutic compound in the highest tolerable dose. This has led to a great number of unwanted toxic side-effects. In addition, these doses mainly stimulated nonspecific lymphokine-activated killer activity through low-affinity IL-2 receptors, which does not lead to systemic immunity. On the other hand, several groups have shown that application of intratumoral low doses of IL-2 can be highly effective against cancer and without toxic side-effects. Significant tumor loads constituting up to 6% of the total body weight of a mouse were eradicated after treatment with low-dose rIL-2 given locally. Furthermore local treatment can lead to eradication of a tumor at a distant site. This type of therapy is effective in many systems namely against different tumor types in mice, hepatocellular carcinoma in guinea-pigs and vulval papilloma and carcinoma and ocular carcinoma in cattle. Low-dose IL-2 is very effective in experimental animals if it is given relatively late after inoculation of the tumor cells. In other words, it seems necessary that some sort of immune reaction has started or is developing before low doses of rIL-2 effectively stimulate it. In fact there is strong evidence that T lymphocytes, both CD4+ and CD8+ cells, are directly involved in the process leading to induction of specific immunity. In our opinion rIL-2 therapy should therefore aim at the stimulation of such (originally weak) specific immune reaction. Under these conditions also systemic immunity can be induced. In conclusion, application of rIL-2 as a modality for cancer treatment is still promising. High priority should be given to a further delineation of the mechanisms involved after local application. The method of giving IL-2 systemically in the highest tolerable dose should be abandoned. Specific stimulation of the immune system by low-dose rIL-2 is a much more promising option. PMID- 8439975 TI - The role of apoptosis in antibody-dependent cellular cytotoxicity. AB - Apoptosis in three lymphoma cell lines has been studied following cytotoxicity induced in vitro by normal human blood lymphocytes utilizing either natural killer (NK) or antibody-dependent cellular cytotoxic (ADCC) mechanisms. Guinea pig L2C leukaemic lymphocytes, but not the human cell lines Daudi and Jurkat, revealed a degree of time- and temperature-dependent apoptotic death upon simple culture in vitro. NK cytotoxicity at low effector:target ratios (E:T) induced both release of 51Cr and apoptosis. However NK cytotoxicity at higher E:T, and ADCC at all E:T, increased the level of 51Cr release while reducing the level of apoptosis. The findings were consistent with the apoptotic process being cut short by intervention of necrotic death. The same characteristics accompanied ADCC whether the effectors were recruited by Fc gamma regions of antibody coating the targets, or by bispecific antibodies attaching one arm to the targets and the other to Fc gamma receptors type III on effectors. This finding, and the high level of cytotoxicity elicited by the bispecific method, confirm the belief that NK cells, in addition to exerting NK cytotoxicity, represent the principal effectors for ADCC among blood mononuclear cells. Our results suggest that NK cells have both apoptotic and necrotic mechanisms available for killing their targets, but use only the latter for ADCC. PMID- 8439976 TI - Enhancement of the antibody-dependent cellular cytotoxicity of human peripheral blood lymphocytes with interleukin-2 and interferon alpha. AB - Antibody-dependent cellular cytotoxicity (ADCC) is regarded as an important mechanism by which monoclonal antibodies (mAb) can exert an antitumour effect in vivo. It may be possible, therefore, to enhance the therapeutic efficacy of mAb by cytokines that are able to enhance the ADCC of human CD3-, CD56+, CD16+ natural killer (NK) cells. We investigated in vitro the effects of recombinant interferon alpha (rIFN alpha) and recombinant interleukin 2 (rIL-2), alone or in combination, on the ADCC of human peripheral blood NK cells. Both cytokines enhanced the ADCC of the human effector cells. rIFN alpha induced a maximally increased ADCC after an exposure of human effector cells to 20 IU/ml for 15-30 min, while rIL-2 induced optimal ADCC after incubation of the cells for 2 days in 20-50 U/ml. We now show that activation of the NK cells with a combination of rIL 2 and rIFN alpha induced significantly higher levels of ADCC than either cytokine alone. The highest ADCC was induced if the cells were first exposed to rIL-2 before rIFN alpha was added to the culture. Culture of NK cells in medium or rIL 2 decreased the expression of Fc gamma RIII (CD16), indicating that intensity of CD16 expression and level of ADCC are not directly correlated, although blocking experiments with a mAb directed against CD16 showed that this Fc gamma R was essential for ADCC of the human effector cells. PMID- 8439977 TI - Therapeutic effects of a synthetic peptide of C-reactive protein in pre-clinical tumor models. AB - Previous studies have shown that multilamellar vesicles (MLV) or other carriers containing purified human C-reactive protein (CRP) have therapeutic activity in preclinical tumor models. Here we evaluated the therapeutic effects of MLV containing novel synthetic peptides, derived from the structure of CRP, on the extent of (a) established lung metastases of fibrosarcoma T241 in C57Bl/6 mice, (b) survival of C57Bl/6 mice bearing established liver metastases of colon carcinoma MCA-38, and (c) primary tumor growth of Renca renal carcinoma in Balb/c mice. In all cases, a single synthetic CRP peptide, RS-83277, demonstrated significant antitumor effects comparable to that seen with intact CRP. Two other synthetic CRP peptides, RS-83287 and RS-83147, showed no therapeutic activity and were comparable to control MLV containing only buffer. None of the peptides contained sequences homologous with that of the phagocyte stimulant, tuftsin. Activity of MLV-encapsulated RS-83277 was dose-dependent, and a comparable dose of the soluble peptide, given either alone or following injection of buffer-MLV, was ineffective. These results demonstrate immunotherapeutic potential for a novel synthetic peptide derived from CRP, and endogenous acute-phase protein. PMID- 8439978 TI - The role of monoclonal antibody A7 as a drug modifier in cancer therapy. AB - An anticancer antibiotic, neocarzinostatin (NCS), was covalently conjugated to the murine monoclonal antibody A7 (mAb A7), which recognizes the glycoprotein on the cell surface of human colon cancer. The biological and pharmacological properties of the conjugate (A7-NCS) were examined and compared with those of unconjugated NCS. A7-NCS exhibited a strong binding and cytotoxicity to the cell and an antigen-specific tumor accumulation. Significant tumoricidal effects in vivo were observed in the antigen-positive tumor-bearing mice treated with A7 NCS, whereas NCS mixed with mAb A7 and NCS alone were relatively ineffective. In the antigen-negative tumor, the tumoricidal effect of A7-NCS was lower than in the antigen-positive tumor. The NCS concentration in blood and tumor were significantly elevated by conjugation to mAb A7. The NCS localization in tumor was higher in the antigen-positive tumor than in the antigen-negative tumor. Death due to acute toxicity was observed at a dose of 20 units (U) NCS in mice treated with unconjugated NCS, whereas toxicity was seen with a much higher dose of NCS (100 U) if the drug was conjugated to the mAb. These findings show that mAb A7 confers more favorable pharmacological properties on an anticancer drug, making it potentially more useful for cancer chemotherapy. PMID- 8439979 TI - Preservation of immune effector cell function following administration of a dose intense 5-fluorouracil-chemotherapy regimen. AB - In a phase II clinical trial of 5-fluorouracil (5FU) plus N-(phosphonacetyl)-L aspartate (PALA) therapy administration, a number of slowly developing clinical responses were observed. Because of this, a variety of immune parameters were sequentially studied in 21 patients on this trial. Of the 21 patients studied, 20 provided sufficient samples to compare baseline with subsequent values, 10 of the 20 patients responded to treatment. Responders and non-responders did not differ in any studied parameter at baseline. After 2 months of therapy, non-specific monocyte cytotoxicity (NSMC), antibody-dependent monocyte cytotoxicity (ADMC) and natural killer (NK) activity were higher in the entire study population, but these increases were not statistically significant. When responders and non responders were evaluated separately, it was apparent that the trend was due solely to the changes observed in the responding patient population. When mean lysis values for each patient group were determined for each studied time point, it was possible to generate a mean area under the cytotoxicity/time curve (AUC) for each studied parameter. NSMC and ADMC did not differ in responders and non responders. However, NK activity was significantly greater by mean AUC analysis (P = 0.006) in the responding group; NK activity was maintained in the responders, but decreased in non-responders. When lymphocyte and monocyte expression of the surface markers beta 2-microglobulin, HLA-DR, CD56, HNK-1, CD16 and interleukin-2 receptor were evaluated, there were no differences among responders and non-responders at baseline by mean AUC analysis or when comparing baseline with non-baseline values. It is concluded that although baseline immunological characteristics do not identify patients who are likely to respond to weekly 5FU and PALA, treatment is not associated with deleterious effects on the immune effector function parameters evaluated in this study, there being no effects on expression of a variety of associated cell-surface molecules. PMID- 8439980 TI - Restricted T cell receptor V-beta and J-beta usage in T cells from interleukin-2 cultured lymphocytes of ovarian and renal carcinomas. AB - Tumour-infiltrating lymphocytes (TIL) are often observed in human tumours and their presence has been correlated with a better prognosis. It has been suggested that TIL are enriched for tumour-specific cytotoxic cells, and TIL activated and expanded in vitro by interleukin-2 (IL-2) are currently used in the therapy of human cancer. We have studied the T cell repertoire in IL-2-expanded TIL cells from patients with ovarian and renal carcinoma using T-cell-receptor-V-beta specific monoclonal antibodies and a polymerase-chain-reaction-based Southern blot technique for analysis of J-beta usage. In TIL lines derived from three of nine patients with ovarian carcinomas and from two of eight patients with renal carcinomas, selective usage of the V-beta 6 or V-beta 5 T-cell receptor gene products was found. The majority of the cells were CD4+, with up to 40% of the T cells utilizing the same V-beta gene. T-cell lines derived from peripheral blood lymphocytes from patients or healthy donors contained normal levels of V-beta subsets. Only moderate levels of V-beta 6+ T cells were detected from freshly isolated TIL and the increase of this subpopulation appeared as a result of in vitro culture. The level of clonal restriction, as measured by the usage of J beta gene segments within the V-beta 5 or V-beta 6 families, was analysed using a recently developed technique based on the polymerase chain reaction. Evidence for restricted J-beta usage was detected only in TIL expanded in vitro, while this was not the case in freshly isolated tumour-derived lymphocytes or T cell lines obtained from peripheral blood lymphocytes. The presence of a population with biased T cell receptor expression in cells derived from tumour tissue could be explained by their activation in vivo as a result of contact with tumour antigens and should be taken into consideration when discussing the therapeutic efficiency of IL-2-expanded TIL. PMID- 8439981 TI - HLA-Dr-expressing CD8bright cells are only temporarily present in the circulation during subcutaneous recombinant interleukin-2 therapy in renal cell carcinoma patients. AB - The effect of subcutaneous recombinant interleukin-2 (rIL-2) therapy on the "activation status" of peripheral blood lymphocytes (PBL) of 17 renal cell carcinoma patients was investigated in a longitudinal study. The expression of the activation markers HLA-Dr and CD25 on cytotoxic T cells, helper T cells, and natural killer (NK) cells, was analysed using two-colour flow cytometry of whole blood samples. In addition, the ability of isolated PBL to proliferate in vitro in response to various stimuli was investigated. The absolute amounts of NK cells and HLA-DR-expressing NK cells increased continuously during the whole course of therapy. The absolute amounts of T cells and HLA-Dr-expressing T cells, however, showed an early increase only during the first 1 or 2 weeks of therapy, after which the absolute amounts of HLA-Dr-expressing T cells decreased. In particular, the absolute amount of HLA-Dr-expressing CD8bright+ T cells was significantly lowered in the second half of therapy. PBL collected on day 7 of therapy (post cycle-1 PBL) showed, as compared to those collected prior to therapy (pretherapy PBL), a decreased proliferative response in vitro after stimulation with phytohaemagglutinin, concanavalin A, soluble CD3 mAb (WT32) or rIL-2. This decreased in vitro response of post-cycle-1 PBL was also reflected in a decrease in the percentage of CD8bright+ T cells expressing HLA-Dr in cultures with rIL-2 or CD3 mAb, in contrast to cultures of pretherapy PBL, which showed an increase of this percentage. We conclude that T cells are the predominantly stimulated subpopulation during the first 2 weeks of subcutaneous rIL-2 therapy. The significant decrease in the absolute amounts of HLA-Dr-expressing T cells in the peripheral blood during the second half of therapy may partly be explained by a decreased responsiveness to rIL-2, but a selective redistribution of HLA-Dr expressing cells may also be involved. PMID- 8439982 TI - Sex hormones and immune dysregulation in multiple myeloma. AB - A group of 49 multiple myeloma patients, 20 men and 29 women, were evaluated. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17 beta-oestradiol (E) and testosterone (T) serum concentrations have been detected by radioimmunoassay. Peripheral blood lymphocyte proliferation in response to phytohaemagglutinin (PHA), concanavalin A (ConA), recombinant interleukin-2 (rIL 2) and dextran sulphate (DxS) was investigated. Our findings provide evidence for two different patterns of sex hormone changes and immune dysfunctions presented differently by male and female multiple myeloma patients. In men increased FSH, LH and E concentrations and an augmented E to T ratio were associated with decreased lymphocyte blastogenic response to PHA, ConA and increased proliferation to rIL-2 and DxS. Female patients with multiple myeloma demonstrated normal values of FSH, LH and T, but a diminished E level and decreased E to T ratio correlated with a lymphocyte normal response to PHA and ConA and augmented blastogenesis to IL-2 and DxS. Our data, while admittedly preliminary, suffice to provide an indication of sex hormone changes in multiple myeloma patients, which could be responsible, at least in part, for the immune dysfunction observed in multiple myeloma. PMID- 8439983 TI - Possible role for cytotoxic lymphocytes in the pathogenesis of acute interstitial nephritis after recombinant interleukin-2 treatment for renal cell cancer. AB - A patient with renal cell cancer developed acute renal failure due to biopsy proven acute tubulo-interstitial nephritis (AIN) in the 6th week of continuous infusion of 9 x 10(6) IU m-2 day-1 recombinant interleukin-2 (rIL-2). We investigated whether the AIN was the result of a cellular cytotoxic reaction induced by the rIL-2 treatment. The cytolytic activity of cryopreserved peripheral blood lymphocytes (PBL), isolated before and at the end of the rIL-2 treatment (at the time of AIN), was studied after 5 days of culture with or without rIL-2 or anti-CD28 and immobilized anti-CD3 antibodies. The PBL isolated before and at the end of the rIL-2 treatment showed cytolytic activity towards a number of allogeneic targets. However, only the PBL isolated at the end of the rIL-2 treatment showed, when stimulated with rIL-2 in vitro, significant cytolytic activity against an autologous renal cell line cultured from the AIN biopsy specimen and against an allogeneic renal cell cancer cell line. These PBL displayed no enhanced killing capacity towards autologous PBL and the melanoma cell line M14. These observations suggest that the AIN may be the result of a cytotoxic lymphocyte-mediated reaction induced by the rIL-2 treatment. PMID- 8439984 TI - Immunization of breast cancer patients using a synthetic sialyl-Tn glycoconjugate plus Detox adjuvant. AB - We have synthesized various formulations that have potential for active specific immunotherapy (ASI) of human cancers. Sialyl-Tn (STn) is a potentially important target structure for ASI because its expression on mucins is a strong, independent predictor of poor prognosis, suggesting that it may have functional significance in the metastatic process. In this first pilot study of synthetic sialyl-Tn hapten conjugated to keyhole limpet hemocyanin (STn-KLH), with Detox adjuvant, toxicity and humoral immunogenicity were assessed in 12 patients with metastatic breast cancer. Toxicity was minimal, restricted to local cutaneous reactions (apart from transient nausea and vomiting following single low-dose cyclophosphamide treatment). Using STn-conjugated human serum albumin in a solid phase enzyme-linked immunosorbent assay, it was shown that all patients developed IgM and IgG specific for the synthetic STn hapten. Following immunization, most patients were shown to develop increased titres of complement-mediated cytotoxic antibodies, partially inhibited by synthetic STn hapten, but not by the related TF hapten. We also detected IgM and IgG antibodies reactive with natural STn determinants expressed on ovine submaxillary mucin, the STn specificity of this reactivity being confirmed by hapten inhibition. Evaluation of clinical efficacy in a small pilot study is difficult. Five patients are alive 12 or more months after entry, and another 4 patients are alive 6 or more months after entry into the study. All 3 patients with known widespread bulky disease progressed despite ASI, 2 having died from widespread cancer. Two patients had partial responses, each lasting 6 months. While several patients had disease stability for 3-10 months, 1 patient with pulmonary metastases remains stable 15 months after entry into the program. PMID- 8439985 TI - T cell killing of human colon carcinomas by monoclonal-antibody-targeted superantigens. AB - The bacterial superantigen staphylococcal enterotoxin A (SEA) induces T cell activation as well as directing activated T cells to kill major histocompatibility-complex-class-II-expressing tumours such as freshly prepared leukemia cells. We now report that conjugates of SEA and the colon-carcinoma reactive mAb C215 mediate T-cell-dependent killing of freshly isolated cells obtained from surgical specimens of human colon carcinomas. Cytotoxicity was observed at nanomolar concentrations of conjugate while no or very low effects were seen with the mAb C215 or SEA alone. Tumour-infiltrating lymphocytes (TIL) did not exert any cytotoxicity against conjugate-treated tumour cells immediately after isolation. In vitro culture of TIL with interleukin-2 and SEA resulted in SEA-mAb-conjugate-dependent killing of freshly isolated tumour cells. This suggests that mAb-SEA conjugates may be of potential use to target T lymphocytes, including TIL, against colon carcinoma cells in vivo. PMID- 8439986 TI - Cure of mice bearing a late-stage, highly metastatic, drug-resistant tumor by adoptive chemoimmunotherapy. AB - We show here that in contrast to BALB/c mice bearing a late-stage, large MOPC-315 plasmacytoma, BALB/c mice bearing a late-stage, large RPC-5 plasmacytoma were not cured by cyclophosphamide therapy (15, 50, 100 or 200 mg/kg). However, most BALB/c mice bearing a late-stage RPC-5 tumor were cured by cyclophosphamide therapy (100 mg/kg) in conjunction with adoptive immunotherapy using tumor infiltrated spleen cells (TISpC) that had been cultured with inactivated RPC-5 tumor cells plus polyethylene glycol 6000, even though this protocol was not effective for the therapy of mice bearing a barely palpable, early-stage RPC-5 tumor. Only a few of the mice that were cured of a late-stage RPC-5 tumor following adoptive chemoimmunotherapy (ACIT) were resistant to a subsequent challenge with RPC-5 tumor cells. However, the challenged mice that had developed progressively growing tumors could then be cured by cyclophosphamide alone when the tumor became large, even though this treatment was not curative for mice bearing a tumor of similar size but not previously treated by ACIT. Thus, the cure by ACIT of BALB/c mice bearing a lethal, late-stage RPC-5 tumor with extensive metastases provides a novel experimental tumor model for investigating the mechanisms by which a chemotherapeutic drug and adoptive cellular immunotherapy can cooperate in causing the complete regression of a large tumor load. PMID- 8439989 TI - Current bibliography of cell calcium prepared by the University of Sheffield Biomedical Information Service. PMID- 8439987 TI - Mechanism of stimulation of human natural killer cytotoxicity by arabinogalactan from Larix occidentalis. AB - Cultures of human peripheral blood mononuclear cells (PBMC) as well as cultures of preseparated peripheral non-adherent cells (PNAC) and monocytes showed enhancement of natural killer (NK) cytotoxicity against K562 tumor cells when pretreated with arabinogalactan from Larix occidentalis for 48-72 h. Lack of enhanced responses of PBMC (37% of donors) did not necessarily mean that PNAC and monocyte cultures were also non-responsive to arabinogalactan treatment. Moreover, PBMC, PNAC and monocytes of individual donors could exhibit various responses to arabinogalactan when cultures derived from bleedings after intervals of several months were assayed. Arabinogalactan-mediated enhancement of NK cytotoxicity was not initiated directly but was found to be governed by the cytokine network. Generally, arabinogalactan pretreatment induced an increased release of interferon gamma (IFN gamma), tumor necrosis factor alpha, interleukin 1 beta (IL-1 beta) and IL-6 but only IFN gamma was involved in enhancement of NK cytotoxicity since cytotoxicity enhancement of PBMC and PNAC but not that of monocytes could be blocked when anti-IFN gamma antibodies were present during pretreatment. The presence of anti-IL-2 antibodies completely blocked NK cytotoxicity enhancement of PBMC and only moderately that of PNAC and monocytes. This blocking effect was also observed when no detectable increase of IL-2 release could be recorded. The receptor specificity of arabinogalactan is not well characterized. Initial information obtained from comparative studies indicated that arabinogalactan presumably interacts with a receptor that showed specificity for a NK-cytotoxicity-enhancing oligo-saccharide from Viscum album extracts since the action of both components was not synergistic but rather competitive. PMID- 8439988 TI - Antitumor effects of a novel monoclonal antibody with high binding affinity to ganglioside GD3. AB - Ganglioside GD3, which is one of the major gangliosides expressed on the cell surface human tumors of neuroectodermal origin, has been studied as a target molecule for passive immunotherapy. We established ten kinds of anti-GD3 monoclonal antibodies (mAb) of the mouse IgG3 subclass by immunization with purified GD3 and melanoma cells. One of the established mAb, KM641, showed major reactivity with GD3 and minor reactivity with GQ1b out of 11 common gangliosides in an enzyme-linked immunosorbent assay. Immunostaining of gangliosides, separated on thin-layer chromatography plates, using KM641 revealed that most of the melanoma cell lines contained immunoreactive GD3 and GD3-lactone at a high level, but only the adrenal gland and the urinary bladder out of 21 human normal tissues had immunoreactive GD3. In immunofluorescence, KM641 bound to a variety of living tumor cell lines especially melanoma cells, including some cell lines to which another anti-GD3 mAb R24, established previously, failed to bind. High affinity binding of KM641 to a tumor cell line was quantified by Scatchard analysis (Kd = 1.9 x 10(-8) M). KM641 exerted tumor-killing activity in the presence of effector cells or complement against melanoma cells expressing GD3 at a high level. Not only natural killer cells but also polymorphonuclear cells were effective as the effector cells in antibody-dependent cellular cytotoxicity. Intravenous injection of KM641 markedly suppressed the tumor growth of a slightly positive cell line, C24.22 (7.2 x 10(5) binding sites/cell), as well as a very GD3-positive cell line, G361 (1.9 x 10(7) binding sites/cell), inoculated intradermally in nude mice. KM641, characterized by a high binding affinity for GD3, has the potential to be a useful agent for passive immunotherapy of human cancer. PMID- 8439990 TI - Estradiol modulation of PMA--and ionomycin-stimulated LH secretion from pituitaries of castrated rats. AB - Quartered pituitaries from castrated (72 h) +/- estradiol (E2)-treated (24 h) rats were used in a perifusion system to investigate estradiol modulation of ionomycin and ionomycin + PMA stimulated LH secretion. Estradiol enhanced the LH responses to GnRH (1 nM) and ionomycin (10 microM), and was necessary for the manifestation of PMA-stimulated (1 microM) LH secretion. Cycloheximide (5 microM) inhibited the E2-enhanced responses to GnRH, ionomycin and PMA. The protein synthesis inhibitor also partially suppressed the GnRH response from pituitaries of castrates, but was totally ineffective against the ionomycin-induced LH secretion. Protein synthesis-dependent, synergistic interactions between PMA and ionomycin were evident from pituitaries of castrates (even though PMA alone was an ineffective secretagogue). Synergistic interactions were not apparent from pituitaries of castrated + E2-treated rats. These results indicate that: (i) estradiol enhances the responsiveness of male gonadotropes to ionomycin and PMA by protein synthesis-dependent mechanisms which appear to mask their synergistic interactions; and (ii) increases in cytoplasmic Ca2+ might be a prerequisite for an expression of the involvement of PKC as a mediator of LH secretion in the absence of high concentrations of estradiol. PMID- 8439991 TI - Independent actions of asparagine and high levels of free Ca2+ in the induction of ornithine decarboxylase. AB - During growth stimulation of cells, Ca2+ and amino acids of the A, ASC and N transport systems are important for the induction of ornithine decarboxylase (ODC, L-ornithine carboxylase, EC 4.1.1.17). In order to clarify the relationship between Ca2+ and amino acids, we studied the induction of ODC by asparagine under three different Ca2+ states in H-35 rat hepatoma cells. First, in normal cells, extracellular Ca2+ above 0.1 mM and 10 mM asparagine separately stimulated ODC activity and their effects were approximately additive. In these normal cells, asparagine could act in the absence of medium Ca2+. TMB-8, a sequestered-Ca2+ release antagonist, had no effect on ODC induction whilst the asparagine action is sensitive to treatment with W7, a Ca-calmodulin antagonist, or lanthanum, a Ca2+ antagonist. Secondly, in cells treated with 0.5 mM EGTA in Ca(2+)-free medium, the asparagine action on ODC induction was blocked but the inhibition could be reversed by the addition of Ca2+ to the medium. Thirdly, ionomycin treatment in the absence of medium Ca2+ did not block the asparagine effect. Furthermore, in ionomycin-treated cells, the presence of high levels of medium Ca2+ increased ODC activity, but this increase was additive to, and could not replace, the action of asparagine. Our results indicate that the asparagine action does not depend on an increase of intracellular free-Ca2+. PMID- 8439992 TI - A discrete Na+/Ca2+ exchange dependent, Ca2+ compartment in cultured neonatal rat heart cells. Characteristics, localization and possible physiological function. AB - A pool of calcium has been identified in cultured neonatal rat heart cells whose exchange is dependent on extracellular sodium and calcium. In the absence of extracellular sodium and calcium this pool retains at least 760 mumol calcium/kg dry weight, which is released upon the introduction of sodium and calcium, with a t1/2 of 4.4 s. Video microscopy experiments of non-stimulated cells showed that the cells, despite the retention of 760 mumoles calcium/kg dry weight, do not develop contracture, indicating that the majority of the pool is not retained in the general cytoplasm. Neither is the pool displaced by lanthanum. Several probes for the sarcoplasmic reticulum were used. Ryanodine (1 microM) had no significant effect on the size of the pool. Caffeine reduced the size of the pool by 60% and thapsigargin, an inhibitor of the sarcoplasmic reticulum Ca-ATPase reduced the content of the pool by 70%. High concentrations of ryanodine (1 mM) reduced the pool even further. The experimental data, in association with recently developed concepts of the diadic region [1], indicate that the pool may reside in the sub sarcolemmal space between the sarcoplasmic reticulum and the sub-sarcolemma. The physiological significance of this pool is discussed. PMID- 8439993 TI - Accuracy and precision of quantitative digital coronary arteriography: observer-, short-, and medium-term variabilities. AB - Coronary arteriograms are increasingly acquired and stored in digital format, which allows instantaneous review of the pictorial data during the cardiac catheterization procedure. To support the angiographer in choosing the optimal sizes of the recanalization devices and studying the efficacy of the recanalization procedures, we have developed a new analytical software package (Automated Coronary Analysis = ACA) on the Philips DCI (-SX) digital cardiac imaging system. The ACA-package allows the objective and reproducible assessment of the morphologic and functional severity of coronary obstructions. Required user interaction is limited to the definition of the start and end points of the coronary segment to be analyzed. Automated contour detection is based on the use of first and second derivative functions along scanlines perpendicular to the automatically computed vessel pathline in the first iteration and perpendicular to the initial contours in the second iteration. These derivative functions have been modified based on the line spread function of the X-ray imaging chain, which is of particular importance for the accurate measurement of small vessel sizes. Phantom studies have indeed demonstrated that vessel sizes down to 0.66 mm can be measured accurately and reproducibly. Inter- and intraobserver variability studies have demonstrated a variability in the obstruction diameter of 0.11 mm and 0.10 mm, respectively, and in the percent diameter stenosis of 5.64% and 3.18%, respectively. These variability studies have been extended to short-term studies with repeated acquisition in the same angiographic views after 5 min and to medium-term studies with repeated acquisition in the initial angiographic views at the end of the catheterization procedures. With these standardized repeated acquisition and analysis procedures, the variabilities in the obstruction diameters increased to 0.19 and 0.18 mm, respectively, and remained below 6% in the percent diameter stenosis (5.61% and 5.28%, respectively). With an analysis time of approximately 15 sec on the DCI-SX, an efficient tool is now available in the catheterization laboratory for the objective and reproducible assessment of vessel dimensions and changes therein as a result of recanalization procedures. PMID- 8439994 TI - Effect of balloon size and stepwise inflation technique on the acute results of Inoue mitral commissurotomy. Inoue Balloon Catheter Investigators. AB - Currently percutaneous transvenous mitral commissurotomy (PTMC) is performed by most operators using stepwise inflation of the Inoue balloon beginning at a small diameter and increasing size by a sequence of inflations to nominal diameter. The effect of balloon size on procedure results using the Inoue balloon has not been evaluated. In 260 patients final balloon inflation was to nominal size in 42% of pts, larger than nominal size (overinflated) in 10%, and less than nominal size (underinflated) in 48% of pts. The average number of inflations was 3 (range 1 9). Pressure gradient and Doppler mitral regurgitation (MR) were assessed after each inflation. When MR increased, further inflations were not done. Patients in whom the balloon was overinflated underwent more balloon inflations than those in whom it was inflated to nominal size (5.0 +/- 2.1 vs. 2.9 +/- 1.4, p < 0.01). Those with balloon underinflation had fewer balloon inflations (2.4 +/- 1.2 vs. 2.9 +/- 1.4, p < 0.01). The post PTMC valve area in patients with overinflation was slightly less than those with nominal inflations (1.6 +/- 0.4 vs. 1.8 +/- 0.7), and with underinflation the valve area was no different compared to nominal inflation. Using a stepwise procedure, if mitral regurgitation was noted to increase after a balloon inflation, the procedure would be stopped even if less than an ideal result was achieved. Fewer inflations were done in patients in whom the balloon was inflated to less than nominal size because of the appearance of mitral regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8439995 TI - Coronary venous retroperfusion of arterial blood for the treatment of acute myocardial ischemia. AB - Synchronized coronary venous retroperfusion of autologous arterial blood was offered to patients referred for medically refractory unstable angina or evolving myocardial infarction with contraindications to thrombolytic therapy. Primary endpoints of angina, ST segment deviation, and two-dimensional echocardiographic systolic wall motion were followed to determine the efficacy of retroperfusion in patients prior to and then during angioplasty, surgical intervention, or pharmacological management, as the clinical picture warranted. Over a 12 month period, 21 patients were referred and 15 received retroperfusion. All experienced full relief of angina (p = 0.008). ST segment deviations and systolic wall motion of ischemic zones were observed to improve (p = 0.06 ST changes; p = 0.0001 wall motion changes) with synchronized retrograde perfusion. During attempts to remove patients from retroperfusion, statistically significant (p < 0.01) reproducible changes in these same endpoints were documented. Retroperfusion appears to improve acute myocardial ischemia. This technique functions well in the intensive care unit environment with only fluoroscopy as technical imaging support. PMID- 8439996 TI - Urokinase infusion after unsuccessful angioplasty in patients with chronic total occlusion of native coronary arteries. AB - Percutaneous transluminal coronary angioplasty (PTCA) is often unsuccessful in patients with chronic total occlusion of coronary arteries. In this study, prolonged urokinase infusion (< or = 24 hr) was administered to 20 patients with chronic total coronary artery occlusion in whom previous PTCA had failed. An intracoronary bolus of urokinase, 120,000 IU, was followed by urokinase infusion, up to 200,000 IU/hr, if necessary, until angiography demonstrated reperfusion and a guiding wire could be advanced past the occlusion site. These results were achieved in 18 of the 20 cases. The two failures occurred early in the series, when the maximum urokinase infusion rate was 120,000 IU/hr. All but one patient with re-established flow subsequently had successful PTCA. Urokinase infusion was well tolerated, with no evidence of intramyocardial hemorrhage. Pretreatment with prolonged urokinase infusion appears to increase the likelihood of successful PTCA in patients with chronic total occlusion of coronary arteries. PMID- 8439997 TI - Cardiac catheterization 1991: a report of the Registry of the Society for Cardiac Angiography and Interventions (SCA&I). AB - This report summarizes the results of the 1991 Registry of the Society for Cardiac Angiography and Interventions in which 72 laboratories reported a total of 92,157 patients, including 17,073 coronary angioplasties, studied between January 1 through December 31, 1991. Complications were similar to previous reports of this Registry. PMID- 8439998 TI - Coronary artery spasm culminating in thrombosis following ergonovine stimulation. AB - A 53-yr-old active man with angina but no angiographically significant obstructive coronary artery disease developed refractory spasm following ergonovine provocation. This resulted in thrombus formation and myocardial infarction. As such, this is the first case in which thrombosis developed at the site of intense coronary artery spasm induced by ergonovine, all of which were documented angiographically. Despite the notable safety of this test, this case re-emphasizes the potential of ergonovine to produce intractable myocardial ischemia and infarction. PMID- 8439999 TI - Radiation-induced stenosis of the left main coronary artery. AB - Isolated left main coronary artery stenosis induced by mediastinal radiation is a well-documented but rare entity. Its clinical manifestations can be latent for many years, but its ominous sequela cannot be ignored. We report here such a patient presenting 16 yr postmediastinal radiation, the longest documented latency to date. PMID- 8440000 TI - Patent ductus arteriosus presenting in old age. AB - This report describes an unusual case of patent ductus arteriosus, presenting in old age. The patient is the oldest living female with patient ductus reported thus far in the medical literature. She initially presented with chest pressure and dyspnea, and subsequently developed subacute bacterial endocarditis and typical angina pectoris with ECG changes, but with normal coronary anatomy. PMID- 8440001 TI - Partial congenital defect of the left pericardium: angiographic diagnosis and treatment by thoracoscopic pericardiectomy: case report. AB - Congenital defects of the pericardium are extremely rare and frequently difficult to diagnose. We present a diagnosis of partial congenital defect of the left pericardium based on a characteristic chest X-ray and left ventriculogram. Additionally, we report findings of a diastolic, migratory coronary stenosis on coronary arteriography which, to date, has not been reported. Confirmation of the diagnosis by mediastinoscopy was followed by thoracoscopic pericardiectomy. PMID- 8440002 TI - Angiographic recognition of a proximal balloon tear during Inoue balloon mitral valvotomy. PMID- 8440003 TI - Repeat balloon occlusion of a pulmonary arteriovenous fistula following cavopulmonary anastomosis in tetralogy of Fallot. AB - A 30-year-old woman with tetralogy of Fallot and cavopulmonary anastomosis (Glenn shunt) presented with a large pulmonary arteriovenous fistula in the right lower lobe. This report describes the successful management following two successive therapeutic balloon embolizations. PMID- 8440004 TI - "Hugging balloon" dilatation: modification and limitation of the technique in oversized vessels. AB - We report a case of "hugging balloon" dilatation of an oversize graft, using two "over-the-wire" balloon catheters via a single 8-F guiding catheter. This combination has not been previously reported, and the limitation of this technique is also discussed. PMID- 8440005 TI - Interpretation of cardiac pathophysiology from pressure waveform analysis: acute aortic insufficiency. PMID- 8440006 TI - Tracker tricks: applications of a novel infusion catheter in coronary intervention. AB - The "Tracker" is a highly trackable and readily exchangeable catheter which can be used to facilitate coronary angioplasty in situations where the guide wire is unable to cross the lesion and is buckling under pressure. In addition it is also useful in assessing the severity of borderline coronary artery stenoses and for local infusion therapy. PMID- 8440007 TI - Balloon catheter systems for PTCA: the importance of the catheter length. AB - The length of a balloon catheter system plays an important role in successfully dilating distal coronary or vein graft stenoses. We herein report a case in which a distal saphenous vein graft lesion could not be reached with a conventional balloon catheter. Factors responsible for this failure included insufficient length. The lesion was eventually reached and successfully dilated with another balloon catheter, which according to the manufacturer had the same length as the first balloon. In order to study this phenomenon eleven balloon catheters were examined using the following measurements: functional catheter length, deliverable catheter length, crossing distance and longitudinal compression. Seven guide catheters were also measured. Results showed variations in standard functional length between several manufacturers, ranging from 132.2-137.8 cm. The deliverable length ranged from 18.3-23.9 cm, crossing distance ranged from 7-37 mm, and the longitudinal compression ranged from 4-30 mm. Guiding catheter length varied among several manufacturers, ranging from 100.6-107 cm. A significant variation was found not only among certain manufacturers, but also among several standard catheters made by one manufacturer. The results of this study suggest that significant variations exist in the length of standard balloon catheters and guiding catheters even among those made by the same manufacturer. These findings can affect the ability to reach a lesion and should be taken into account, especially when attempting to perform angioplasty of stenoses located in the distal portion of a coronary artery or saphenous vein graft. PMID- 8440008 TI - Rupture and entrapment of a balloon catheter in the left anterior descending artery: fluoroscopic appearance of impending balloon failure. AB - Rupture of an angioplasty balloon in an undilated left anterior descending coronary stenosis resulted in entrapment of the balloon requiring surgical removal. The balloon was found to have a circumferential tear. The fluoroscopic appearance of impending balloon rupture is demonstrated. It is suggested that when faced with an unyielding stenosis, inflation pressure sufficient to cause impending balloon failure should be avoided. PMID- 8440009 TI - New technique for right heart catheterization using a Mullins' sheath. AB - A new technique for right heart catheterization using a Mullins' sheath is described. This device allows a Swan-Ganz catheter to reach pulmonary artery position easily and permits simultaneous pressure recordings in right heart chambers, thus avoiding a double venous puncture and two catheters. This new technique, its indications, and our experience in 29 patients are described. It is most useful in patients with severe pulmonary hypertension and in those conditions in which accurate right heart pressure measurements are needed. PMID- 8440010 TI - Coronary stenting through 6 French guiding catheters. AB - Most stent implantation procedures currently require the use of large-diameter guiding catheters. We describe our preliminary successful experience with 6 French guiding catheters to deliver balloon-expandable Palmaz-Schatz stents to the coronary arteries. PMID- 8440011 TI - Right brachial arterial sheath insertion. PMID- 8440012 TI - Complete heart block complicating retrograde left heart catheterization. PMID- 8440013 TI - MOVC as cause of Budd-Chiari syndrome. PMID- 8440014 TI - Inherited predisposition to thrombosis. PMID- 8440015 TI - Structure(?) and function of acidic transcription activators. PMID- 8440016 TI - CLN3 functions in both daughter and mother cells of S. cerevisiae. PMID- 8440017 TI - A suppressor of cln3 for size control. PMID- 8440018 TI - pelle encodes a protein kinase required to establish dorsoventral polarity in the Drosophila embryo. AB - The pelle gene is required for the nuclear import of dorsal protein that establishes dorsoventral polarity in Drosophila embryos. We report here the genetic mapping and molecular characterization of pelle. DNA sequence analysis revealed that pelle encodes a protein of 501 amino acids, the last 292 of which comprise a protein kinase catalytic domain. Microinjection of in vitro synthesized transcripts containing site-directed mutations indicates that the kinase catalytic domain is required for biological activity. This domain is most similar to that of the rat and mos protein kinases and is predicted to have a serine and threonine specificity. These results provide direct evidence for the role of phosphorylation in the in vivo regulation of a rel-like transcription factor. PMID- 8440019 TI - Organizing activity of wingless protein in Drosophila. AB - The adult appendages of Drosophila are formed from imaginal discs, sheets of epithelial cells that proliferate during larval development and differentiate during metamorphosis. wingless (wg, DWnt-1) protein, a putative signaling molecule, is expressed only in prospective ventral cells in each of the leg discs. To test the role of wg, we have generated randomly positioned clones of cells that express wg protein constitutively. Clones that arise in the prospective ventral portions of the leg discs develop normally. In contrast, dorsally situated clones give rise to ventrolateral patterns and exert a ventralizing influence on neighboring wild-type tissue. We propose that wg protein organizes leg pattern along the dorsoventral axis by conferring ventral positional information within the disc. PMID- 8440020 TI - Induction of cell differentiation by human immunodeficiency virus 1 vpr. AB - Cell lines from rhabdomyosarcomas, which are tumors of muscle origin, have been used as models of CD4-independent HIV infection. These cell lines can be induced to differentiate in vitro. We report here that the vpr gene of HIV1 is sufficient for the differentiation of the human rhabdomyosarcoma cell line TE671. Differentiated cells are characterized by great enlargement, altered morphology, lack of replication, and high level expression of the muscle-specific protein myosin. We have also observed the morphological differentiation and inhibition of proliferation of two other transformed cell lines. vpr-transfected cells remain fully viable in culture for extended periods. These observations elucidate a potential role for vpr in the virus life cycle and raise the possibility that some aspects of HIV-induced pathologies may be caused by a disturbance of cells by vpr. PMID- 8440021 TI - Genetic evidence that an activation domain of GAL4 does not require acidity and may form a beta sheet. AB - Regulation of gene expression in eukaryotes relies on intricate protein-protein interactions. Transcription of the galactose genes in yeast has been a productive model for this type of interaction. The positive activator in this system, GAL4, has a bifunctional C-terminus. It contains both a prototypic acidic activation domain and a region that binds the negative regulator, GAL80. We have taken advantage of this colocalization of functions to subject the region to a constrained mutagenesis analysis: one function was maintained, while the other one was altered. This analysis and the experiments it suggested have led us to two conclusions: first, the acidic amino acids are not, as commonly thought, required for activation; second, this region is not unstructured or alpha helical, but its function may require a beta sheet. PMID- 8440022 TI - The acidic activation domains of the GCN4 and GAL4 proteins are not alpha helical but form beta sheets. AB - The most common class of activation domains, the so-called acidic activators, has been proposed either to adopt an amphipathic alpha-helical structure or to exist as unstructured "acid blobs." However, genetic analysis of an acidic activation domain in the yeast GAL4 protein has suggested that the structure of the activation region is a beta sheet. To distinguish between these models, we conducted a biophysical analysis of peptides corresponding to the yeast GAL4 and GCN4 acidic activation domains. Circular dichroism spectroscopy shows that the peptides are not alpha helical, but that they can undergo a transition to a structure that is almost 100% beta sheet in character in slightly acidic solution. We also show that the artificial acidic activator AH has structural properties that are markedly different from the natural GAL4 and GCN4 domains and does not adopt a beta-rich structure at reduced pH. PMID- 8440023 TI - Actin-binding protein is a component of bovine erythrocytes. AB - Actin-binding protein (ABP) is a well-characterized polypeptide capable of crosslinking filamentous actin. To date, this polypeptide has been shown to exist in a number of tissues and cultured cell lines. This report shows that by using a panel of three monoclonal antibodies for immunoblotting and immunofluorescence analysis, that ABP is present in bovine erythrocytes. Moreover, the data obtained suggest that this protein is a component of the erythrocyte membrane skeleton. Additionally, bovine erythrocyte ABP is shown to possess both an apparent molecular weight and an isoelectric point identical to that of bovine smooth muscle filamin, implying that these two polypeptides are identical. PMID- 8440024 TI - Morphology of nexin links in relation to interdoublet sliding in the sperm flagellum. AB - In this work, we examine whether the "nexin" linkages of the flagellum can extend in length to accommodate interdoublet sliding. Flagellar bends of large angle were induced in bull spermatozoa by hypotonic treatment. It is argued that this produces large interdoublet displacements that are, nevertheless, still within physiological limits. Such flagella were examined by the rapid-freeze, deep-etch technique and the nexin linkages identified by their position in relation to the inner dynein arms and by their straplike, bipartite, morphology. They were found to bridge perpendicularly (or occasionally at an angle) between the A- and B tubules of adjacent doublets. The nexin linkages were no more than approximately nm in length, even in regions in which approximately 200 nm of sliding could be inferred. Variable registration between adjacent nexin rows gave some further support to the assumption that sliding had indeed taken place. From this, it is concluded that elastic deformation of the links, such as would accommodate interdoublet sliding, does not occur; some form of displacement must occur between nexin and the adjacent B-tubule. PMID- 8440025 TI - Incorporation of microinjected mutant and wildtype recombinant tropomyosins into stress fibers in fibroblasts. AB - The structural requirements for assembly of tropomyosin into stress fibers were investigated by microinjecting wildtype and four mutant striated chicken muscle alpha-tropomyosins expressed in E. coli as fusion and nonfusion proteins into cultured rat embryo fibroblasts, followed by localization of tropomyosin using indirect immunofluorescence. The results show that the determinants for stress fiber incorporation in living cells correlate with the in vitro actin affinity of these tropomyosins. Wildtype recombinant protein incorporated into stress fibers both when the amino terminus was unacetylated and when it was blocked with an 80 residue fusion protein [Hitchcock-DeGregori, S.E., and Heald, R.W. (1987): J. Biol. Chem. 262:9730-9735]. The pattern of incorporation was indistinguishable from that of tropomyosin isolated from chicken pectoral muscle. The striated alpha-tropomyosin incorporated into stress fibers, even though this isoform is not found in nonmuscle cells. Three recombinant mutant tropomyosins in which one half, two-thirds, or one actin binding site was deleted were tested [Hitchcock DeGregori, S.E., and Varnell, T.A. (1990): J. Mol. Biol. 214:885-896]. Only the fusion protein with a full actin binding site deleted incorporated into stress fibers. However, the unacetylated, nonfusion proteins with one half and one actin binding site deleted incorporated into stress fibers, consistent with the ability of troponin to promote the actin binding in vitro. A fourth mutant, in which the conserved amino-terminal nine residues were deleted, did not incorporate into stress fibers, consistent with the complete loss of function of this mutant [Cho, Y.J., Liu, J., and Hitchcock-DeGregori, S.E. (1990): J. Biol. Chem. 265:538-545]. PMID- 8440026 TI - PDGF and neomycin induce similar changes in the actin cytoskeleton in human fibroblasts. AB - The addition of platelet-derived growth factor (PDGF) to serum-starved fibroblasts induces increased motility, formation of lamellipodia, increased ruffling activity, and actin ring structures associated with dorsal ruffles. Involvement of the phosphatidylinositol cycle (PI-cycle) in these morphological changes was investigated by observing the effects of neomycin, an inhibitor of the PI-cycle, on cultured human foreskin fibroblasts. The role of actin in the changes was investigated by using cytochalasin D (CD). Actin in detergent extracted cells was labelled with TRITC-phalloidin and examined with fluorescence microscopy. Using PDGF and neomycin simultaneously potentiated lamellipodia formation, ruffling activity, as well as the number of cells with actin rings. Furthermore, neomycin by itself induced morphological changes similar to those induced by PDGF. Quantitation of actin rings showed dose and time dependency for PDGF and neomycin respectively, with a maximal number of cells containing rings after 15 min of exposure to either 3.5 mM neomycin or 10 ng PDGF/ml. Comparing the two substances, PDGF induced ring formation in a greater number of cells. These processes were inhibited by the presence of CD. PDGF- and neomycin-induced changes in the actin cytoskeleton were also observed in human embryonic lung fibroblasts, human glial cells, and embryonic mouse fibroblasts, all of which are known to express PDGF-receptors. In conclusion, the present study indicates that an increased turnover of the PI-cycle is not essential for the changes in actin organization induced by PDGF. PMID- 8440027 TI - Cytoskeletal sheets of mammalian eggs and embryos: a lattice-like network of intermediate filaments. AB - Mammalian eggs and embryos possess a major cytoskeletal network composed of large planar "sheets" distributed throughout the cytoplasm. Cytoskeletal sheets are found neither in mammalian somatic cells nor in eggs or embryos of non-mammals. In this study, we have investigated the structural composition of the sheets in eggs and embryos of the golden Syrian hamster by (1) analysis of replicas from quick-frozen, deep-etched specimens, (2) analysis of thick, resin-embedded specimens using an intermediate voltage electron microscope (IVEM), (3) laser diffraction of EM images, (4) differential extraction with detergents, and (5) immunocytochemistry. Our results indicate that each sheet is composed of two closely apposed arrays of 10-nm filaments. Each filament within an array is held in register with its neighbor by lateral cross-bridges and the two parallel arrays of filaments are interconnected by periodic cross-bridges about 20 nm in length. Laser diffraction of negatives from IVEM images indicates that each array is composed of fibers that form a square lattice, and the two arrays are positioned in register by cross-bridges forming a single sheet. This lattice forms the skeleton of the sheets which is covered with a tightly packed layer of particulate material. By incubation in media containing different ratios of mixed micelle detergents, it is possible to remove components sequentially from the sheets and to extract the particulate material. Immunocytochemical localization demonstrates that the sheets bind antibodies to keratin, and to a small extent actin, but do not bind antibodies to vimentin or tubulin. Examination of sheets within embryos at the time of embryonic compaction demonstrates that the sheets begin to fragment and disassemble in regions of blastomeres where desmosomes form, but undergo no structural alterations in interior and basal surfaces of the blastomeres. In regions of blastomere-blastomere contact the sheets fragment and associate with granules resembling keratohyalin granules found in keratinocytes. PMID- 8440028 TI - Intestinal parasitic infections and urbanization. AB - About a third of the population in the cities of developing countries live in slums and shanty towns. By the year 2000 it is estimated that this number will grow to 2200 million, and by 2025 about 57% of the population in developing countries will be in urban areas. The prevalence of infections caused by Entamoeba histolytica and Giardia intestinalis and the prevalence and intensity of Ascaris lumbricoides and Trichuris trichiura infections may increase among the rural populations who are migrating to these urban and suburban settings owing to the favourable conditions for transmission. Urgent consideration should therefore be given to improving sanitation in deprived urban areas and to treating periodically these populations to reduce the worm burden, especially in school age children. PMID- 8440029 TI - Nomenclature of amyloid and amyloidosis. WHO-IUIS Nomenclature Sub-Committee. AB - This classification of amyloid and amyloidosis is based on the amyloid fibril proteins, followed by a designation of the fibril protein precursor. Additional information includes the protein type or variant (where applicable) and the clinical diagnosis. PMID- 8440030 TI - Nomenclature for T-cell receptor (TCR) gene segments of the immune system. WHO IUIS Nomenclature Sub-Committee on TCR Designation. AB - The recommended procedures and criteria for T-cell receptor (TCR) designations are described. The officially adopted designations are for the TCR A, B, D and G loci and for V, D, J and C segments. PMID- 8440031 TI - Long-acting chloramphenicol for bacterial meningitis. PMID- 8440032 TI - Cholera and international trade in food. PMID- 8440033 TI - Rapid evaluation methods (REM) of health services performance: methodological observations. AB - The rapid evaluation method (REM) was developed by WHO in order to assess the performance and quality of health care services, identify operational problems, and assist in taking managerial action. It was tested in five developing countries (Botswana, Madagascar, Papua New Guinea, Uganda and Zambia) between 1988 and 1991. REM consists of a set of observation- and survey-based diagnostic activities, carried out mainly in health care facilities. The article describes the various steps of REM, methodological issues such as setting objectives and using an issue-information matrix, preparation of survey instruments, use of computer software (Epi Info), data quality control, fieldwork, and the use of data to produce useful information for decision-makers. REM aims at bringing prompt and relevant information to planners and decision-makers who need it for a specific purpose. In the present examples, REM provided information for preparing a programme proposal for external funding, for establishing baseline data for a situation analysis, and for assessing staff performance after extensive training in order to improve the curriculum. PMID- 8440034 TI - Structured observations of hygiene behaviours in Burkina Faso: validity, variability, and utility. AB - The use of observation techniques has been promoted for the study of hygiene practices; however, questions still remain about the validity and repeatability of such techniques. In this article we compare data on hygiene behaviours obtained from questionnaires with data obtained using a structured observation approach and examine the repeatability of structured observations of behaviours and spot observations of environmental conditions. Poor agreement between questionnaire responses and observations was found for child defecation and stool disposal practices (kappa statistic: 0.25 and 0.28, respectively). There was evidence of over-reporting of "good" behaviours (P < 0.0001). Repeated observations of child defecation and stool disposal behaviours showed better agreement (kappa statistic: 0.76 and 0.62, respectively) based on small sample sizes. These findings suggest that our questionnaire data are less valid than data obtained by direct observation. However, different approaches to questioning may be less prone to over-reporting of "good" behaviours than our approach. Further research into the validity of different forms of question is warranted. Behaviours and conditions related to hygiene vary. Observations may be useful in determining the frequency of different behaviours/conditions in the community. However, individual practices may be too variable to assign individuals to exposed and non-exposed groups for the purpose of identifying links with health outcomes. Further studies on the variability of behaviours and the repeatability of observations are therefore needed. PMID- 8440035 TI - A vaccination survey using the EPI methodology ot evaluate the impact of a child health outreach programme in an urban area of South Africa. AB - A community-based survey of the vaccination status of children aged 12-23 months was conducted to evaluate the impact of a child health outreach programme on vaccination coverage in Alexandra township, South Africa. The EPI cluster sampling technique was adapted for this purpose. The sample size, including the number of clusters and the number of units per cluster, was increased to permit stratification of the data and comparison of the results with those obtained in a study conducted prior to the introduction of the outreach services in 1988. At the time of the survey interview, 67% of the children were fully vaccinated (78% against measles) and by 1 year of age, 58% were fully vaccinated (69% against measles). The increase in coverage since the introduction of the programme was statistically significant only for measles (Student's t-test, P < 0.01). A total of 75% of children living in formal dwellings, compared with 51% living in informal dwellings, were fully vaccinated by interview (Fisher's exact test, two tailed, P < 0.0001). Mothers from informal dwellings had a 1.88 times greater chance of not knowing about the outreach services (P < 0.001). Children whose mothers knew where vaccinations were given, attended postnatal clinics, used the outreach services, possessed a road-to-health card from the Alexandra Health Centre, and who resided in a formal dwelling all had a higher chance of being vaccinated. PMID- 8440036 TI - BCG vaccination of full-term infants with chronic intrauterine malnutrition: influence of immunization age on development of post-vaccination, delayed tuberculin hypersensitivity. AB - To determine the effect of intrauterine growth retardation (IUGR) on the response to BCG vaccination, we evaluated the specific delayed tuberculin hypersensitivity of 57 full-term infants with symmetric IUGR (SGA or small for gestational age) and 52 full-term infants with normal intrauterine growth (AGA or appropriate for gestational age). The infants were evaluated using post-vaccination skin tests to tuberculin purified protein derivative (PPD) and tuberculin lymphocyte transformation tests. Using a positive response to the skin test as an indicator of delayed hypersensitivity, we found that the rate of response to BCG in the SGA and AGA groups was similar. A total of 65% of infants with IUGR responded to BCG vaccination. The response rate among SGA infants who were vaccinated at 5 days of age, about 26 days of age (weight > or = 2500 g), 3 months of age, and 6 months of age was 68%, 47%, 69%, and 88%, respectively. The overall response rate for infants with no IUGR was 71%; the rate response to BCG vaccination among this group was 52% (those vaccinated at 5 days of age), 90% (3 months of age), and 80% (6 months of age). Our data suggest that the immunogenicity of BCG vaccine is similar in term infants who have normal or abnormal intrauterine growth and the presence of IUGR should not be a reason for delaying BCG vaccination. PMID- 8440037 TI - The resurgence of lymphatic filariasis in the Nile delta. AB - A study of 325,000 residents of 314 villages in six governorates of the Nile delta area of Egypt revealed that the prevalence of lymphatic filariasis increased from < 1% in 1965 to > 20% in 1991, especially in the governorates of Qalyubiya, Monufiya, Dakhaliya, and Giza. The distribution of the communites with endemic filariasis is focal. Clusters of villages with high prevalences are surrounded by others in which the disease is absent, although their environmental, social, and agricultural features appear similar. The article analyses why the significant decline in filariasis between 1945 and 1965 in Egypt has been followed by a resurgence of the disease. PMID- 8440038 TI - Bancroftian filariasis in an isolated hunter-gatherer shifting horticulturist group in Papua New Guinea. AB - A survey for Wuchereria bancrofti microfilaraemia using membrane filtration was carried out among the Hagahai, a recently contacted Papua New Guinea group of hunter-gatherer shifting horticulturists. Adult men had a significantly higher microfilaraemia rate than women. Children aged > 15 years had significantly fewer infections than adults and the microfilaraemia densities were considerably lower. Two subjects exhibited matutinal microfilarial periodicity, peaking at approximately 06 h 00. The possible reasons for the epidemiological and microfilarial findings are discussed. PMID- 8440039 TI - Epidemiology of rheumatic fever and rheumatic heart disease in a rural community in northern India. AB - The epidemiology of rheumatic fever and rheumatic heart disease in a rural community (total population 114,610) in northern India was studied by setting up a registry based on primary health care centres. Health workers and schoolteachers were trained to identify suspected patients in school and village surveys (121 villages). Medical specialists screened 5-15-year-olds (n = 31,200). The population was followed up for 3 years (from March 1988 to March 1991). All suspected and registered cases were investigated by serial echocardiography and Doppler ultrasonography at a tertiary care centre. A total of 102 cases were confirmed to have rheumatic fever/rheumatic heart disease (prevalence, 0.09%); 66 were aged 5-15 years (prevalence, 0.21%). A total of 48 patients (24 males, 24 females; mean age, 12.11 +/- 3.7 years) were diagnosed to have a possible first attack of rheumatic fever (incidence, 0.54 per 1000 per year). Arthritis was observed in 36 (75%) and carditis in 18 (37.5%) of cases. Prolapse of the anterior mitral leaflet into the left atrium occurred in 5 (22%) cases with carditis. Mitral regurgitation was observed in all 18 cases of carditis; over the period of observation it disappeared in three cases and progressed to mitral stenosis in a further three. A total of 22 patients (11 males, 11 females; mean age, 19.41 +/- 8.1 years) were registered as rheumatic fever recurrences, and 32 patients (18 females, 14 males; mean age, 22.1 +/- 10.1 years) had chronic rheumatic heart disease. Of those with recurrences, 9 (41%) had carditis and 11 (50%) had arthritis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8440040 TI - A 3-year follow-up study of coronary heart disease in Delhi. AB - A follow-up study of coronary heart disease (CHD) was carried out among adults in Delhi 3 years after an initial community-based epidemiological survey of the same population. A total of 575 of the 814 cases of CHD detected clinically and by electrocardiogram (ECG) in the initial survey took part. On re-examination of the original cohort of 4151 adults who were free of CHD both clinically and by ECG in the initial survey, 245 new cases of CHD were detected - 73 on a clinical basis (21 with myocardial infarction and 52 with angina pectoris) and 172 by ECG (13 with myocardial infarction and 159 with probable CHD based on ST and T changes). The overall incidence of CHD was 19.7 per 1000 (males, 17.3 per 1000; females, 21.0 per 1000). The incidence on a clinical basis was 5.9 per 1000 (males, 6.5 per 1000; females, 5.5 per 1000) compared with 13.8 per 1000 by ECG (males, 10.8 per 1000; females, 15.5 per 1000). Although the incidence of myocardial infarction was higher in men (3.6 per 1000) than women (2.2 per 1000), the incidence of angina pectoris was 36.5% higher in women (18.7 per 1000) than in men (13.7 per 1000). Hypercholesterolaemia and systemic hypertension were the commonest risk factors in the 245 new cases. PMID- 8440041 TI - Risk factors for mortality in the Bangladesh cyclone of 1991. AB - Cyclones continue to pose a dangerous threat to the coastal populations of Bangladesh, despite improvements in disaster control procedures. After 138,000 persons died in the April 1991 cyclone, we carried out a rapid epidemiological assessment to determine factors associated with cyclone-related mortality and to identify prevention strategies. A nonrandom survey of 45 housing clusters comprising 1123 persons showed that mortality was greatest among under-10-year olds (26%) and women older than 40 years (31%). Nearly 22% of persons who did not reach a concrete or brick structure died, whereas all persons who sought refuge in such structures survived. Future cyclone-associated mortality in Bangladesh could be prevented by more effective warnings leading to an earlier response, better access to designated cyclone shelters, and improved preparedness in high risk communities. In particular, deaths among women and under-10-year-olds could be reduced by ensuring that they are given special attention by families, neighbours, local authorities, and especially those in charge of early warnings and emergency evacuation. PMID- 8440042 TI - Contaminated weaning food: a major risk factor for diarrhoea and associated malnutrition. AB - Infections and the malnutrition associated with them are responsible for a significant proportion of the 13 million deaths among infants and children under 5 years of age worldwide each year. After respiratory infections, diarrhoeal diseases are the commonest illnesses and have the greatest negative impact upon the growth of infants and young children. The causes of diarrhoeal diseases have traditionally been ascribed to water supply and sanitation. In attempts to prevent such diseases, efforts by governments and nongovernmental organizations have been focused on and sometimes limited to improving water supply and sanitation as well as promoting and protecting breast-feeding. Based on studies reported in the literature, this review article demonstrates that weaning foods prepared under unhygienic conditions are frequently heavily contaminated with pathogens and thus are a major factor in the cause of diarrhoeal diseases and associated malnutrition. In the light of the evidence presented, it appears that current efforts are not sufficient to prevent diarrhoeal diseases: education of mothers in food safety principles, particularly weaning food, must also receive high priority. Educational programmes based on the hazard-analysis-critical control-point approach, taking into consideration also sociocultural factors, should be integrated into all national infant feeding or food and nutrition programmes. PMID- 8440044 TI - Liver function in UK patients with oral lichen planus. PMID- 8440043 TI - Measles control in developing and developed countries: the case for a two-dose policy. AB - Despite major reductions in the incidence of measles and its complications, measles control with a single dose of the currently used. Schwarz strain vaccine has failed to eradicate the disease in the developed countries. In developing countries an enormous toll of measles deaths and disability continues, despite considerable efforts and increasing immunization coverage. Empirical evidence from a number of countries suggests that a two-dose measles vaccination programme, by improving individual protection and heard immunity can make a major contribution to measles control and elimination of local circulation of the disease. Cost-benefit analysis also supports the two-dose schedule in terms of savings in health costs, and total costs to society. A two-dose measles vaccination programme is therefore an essential component of preventive health care in developing, as well as developed countries for the 1990s. PMID- 8440045 TI - Medical audit--need for a positive commitment. AB - To assess the effectiveness of a case note audit in two dermatology units, the effect of policy changes in clinical practice, made following the identification of deficiencies in practice by an initial audit in 1987, were evaluated 2 years later by repeating the audit process, i.e. 'completing the audit circle'. The case notes of 200 new referrals of patients with psoriasis were audited, using a criteria set of 18 questions devised by a group of 66 dermatologists, in 1987 and again in 1989. Following the initial audit in 1987, policy changes were made at one centre (B) but not at the other (A). In the centre where no policy changes were agreed (A) there was no improvement in record keeping when re-audited in 1989. In centre (B), where a number of policy decisions were taken and protocols established, there was a highly significant improvement in record keeping (60% satisfactory completion of the criteria set in 1987 increased to 74% in 1989, P < 0.0001). Doctors in training grades performed best and were most responsive to the policy changes. The effectiveness of a criterion-based audit depends on a commitment to change, where indicated, and regular reinforcement of new policies at all levels of medical staff. PMID- 8440046 TI - The march of melanoma. PMID- 8440047 TI - Measurement of plaque thickness and evaporative water loss in psoriasis with PUVA and dithranol treatment. AB - Pre-treatment plaque thickness determined the rate at which psoriasis responded to PUVA treatment, taking longer with thicker plaques. For dithranol, the rate of response to treatment was independent of pre-treatment plaque thickness. Plaques of psoriasis that showed the greatest evaporative water loss before treatment took longest to clear with PUVA. At the time of clinical clearing the water loss had returned to that of adjacent, uninvolved skin. With dithranol the evaporative water loss did not return to normal levels but remained considerably elevated when the plaque was clinically clear. PMID- 8440048 TI - Ultra-short topical treatment of pityriasis versicolor with 2.5% bifonazole cream. AB - The therapeutic efficacy of a preparation containing 2.5% bifonazole was investigated by comparing three different treatment modalities--A, B, and C. Group A used bifonazole only on Days 1, 2 and 3, and the Group C on Days 1, 3 and 5. Of the patients in Group A 56% had a negative mycological examination at the end of the study. The results obtained in Groups B and C were not significantly different: 92% of the patients had a negative mycological examination at the end of the study. Electron microscope (EM) studies showed morphological alterations such as loss of cytoplasmic organization with shrinkage and folding of the cell membranes after 1 week of treatment only in Groups B and C. We conclude that 2.5% bifonazole is a highly effective treatment for Pityrosporum ovale infection when applied using a 3-day schedule. PMID- 8440049 TI - Cutaneous malignancy related to cyclosporin A therapy. PMID- 8440050 TI - The relationship of psoriasis to malignancy: a clinical report. AB - A large variety of cutaneous reactions to malignancy have been described but to our knowledge none include psoriasis. Two cases of psoriasiform reactions in association with malignancy were first documented by Braverman, and Bazex's syndrome is now well documented in the literature. Both conditions, although clinically psoriasiform, are said to demonstrate an eczematous histology. A number of patients with psoriasis and malignancy have presented to us in the Dermatology Department. The appearance or behaviour of their psoriasis appeared to be linked to their malignancy. We have collected them together to report on this phenomenon which appears infrequently in the literature. PMID- 8440051 TI - Keratosis pilaris decalvans non-atrophicans. AB - A patient is described who presented with an eruption of tiny follicular keratotic papules on the limbs and the trunk accompanied by profuse hair loss. Histologically, a diagnosis of keratosis pilaris was made. The eruption cleared spontaneously in 3 months with complete regrowth of hair. Neither atrophy nor scarring remained. This appears to be the first reported case of keratosis pilaris decalvans non-atrophicans. PMID- 8440052 TI - Acute febrile neutrophilic dermatosis in association with erythema nodosum and sarcoidosis. AB - We report two cases of simultaneous Sweet's syndrome and erythema nodosum. We believe this to be a real association rather than the extension of the neutrophilic infiltrate of Sweet's syndrome into the subcutaneous fat. In one of our cases, concurrent erythema nodosum and Sweet's syndrome was a presentation of sarcoidosis with bilateral hilar lymphadenopathy. To our knowledge, this is the first report of Sweet's syndrome with sarcoidosis. PMID- 8440053 TI - Familial melanoma. AB - The presence of large numbers of moles, atypical in appearance and distribution typifies the atypical mole syndrome. The syndrome may occur in one individual alone or in an autosomal-dominant fashion in his/her family. The presence of this phenotype indicates an increased risk of melanoma, although the risk varies according to the presence or absence of a family history. The classification devised by Kraemer et al. works well in estimating the risk of melanomas but is, as yet, not fully evaluated. The diagnosis of the syndrome is essentially clinical, necessitating the consideration of various aspects of phenotype such as total mole count, distribution, clinical appearance of the moles, the age of onset, site, and number of melanomas. It is always helpful to screen first-degree and second-degree relatives if there is a family history of moleyness or melanoma. Small numbers of clinically and, sometimes histologically dysplastic naevi may occur in normal individuals. The vast majority of these probably regress as do totally banal naevi, although a low percentage will result in a melanoma. Those patients should be questioned to establish the existence of a family history of increased numbers of moles and melanoma. They should also be thoroughly examined for the presence of other signs of the syndrome: increased total mole count, iris freckles etc. In the absence of either a family history or these additional clinical features it is unlikely that these individuals have 'the syndrome'. Common sense advice about sun avoidance and self-examination should be given. It is important to distinguish this from the atypical mole syndrome (AMS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8440054 TI - Urticated annular erythema: a new manifestation of Sjogren's syndrome. AB - A patient with a unique urticated annular erythema associated with Sjogren's syndrome and some features of systemic lupus erythematosus (SLE) is reported. There has been one previous report of a similar eruption occurring in a patient with Sjogren's syndrome. PMID- 8440055 TI - Piroxicam photosensitivity associated with vesicular hand dermatitis. AB - A case of piroxicam photosensitivity in a 42-year-old man is reported. While he was taking piroxicam, eczematous skin lesions on sun-exposed skin and vesicular hand dermatitis on the finger webs and palms developed. He showed a lowered minimal erythema dose (MED) to UVA when a rechallenge with piroxicam was attempted. Photopatch testing with piroxicam was positive. PMID- 8440056 TI - A case of Achenbach's syndrome. AB - Achenbach's syndrome is a rarely reported clinical entity consisting of spontaneous or mechanically induced haematomas on the volar aspects of fingers which are associated with burning pain and swelling of the digits. We describe such a case in a 46-year-old nursing sister. PMID- 8440057 TI - Improvement of yellow nail syndrome with oral zinc supplementation. AB - An unusual case of yellow nail syndrome (YNS) is reported. Total resolution of yellow nails and lymphoedema was observed following oral zinc supplementation for 2 years. A few years later, the patient developed a classical seropositive rheumatoid arthritis (RA). YNS, alone or associated with RA remains a rare clinical condition. The reported beneficial effects of zinc supplementation in YNS, as well as in several other pathological conditions, raise interest about the role of this trace element and its potential therapeutic implications and suggest further investigations are necessary. PMID- 8440058 TI - Subcutaneous sarcoidosis. AB - Subcutaneous sarcoid appears to be rare, particularly in Caucasians. When it does occur, it usually heralds systemic involvement. A case of subcutaneous sarcoid is reported, which is unusual both in its extent, and by its lack of demonstrable extra-cutaneous disease. Cutaneous sarcoid is well recognized, but subcutaneous sarcoid has rarely been described. We report only the fourth case of subcutaneous sarcoid from the UK. PMID- 8440059 TI - Transcutaneous electronic nerve stimulation in the treatment of generalized pruritus. AB - Generalized pruritus is a notoriously troublesome condition for both patient and dermatologist. This paper describes the favourable therapeutic effect of transcutaneous electrical nerve stimulation (TENS) in two elderly patients with severe chronic generalized pruritus unresponsive to other treatment. The therapeutic application of TENS to the treatment of generalized pruritus has not previously been described. PMID- 8440060 TI - Isotretinoin-associated pseudoporphyria. AB - We present two patients who developed pseudoporphyria whilst taking isotretinoin (Roaccutane). At that time, both patients were receiving other agents which could be incriminated as causing their pseudoporphyria. However, it is significant that these other agents had been longstanding and that the porphyria-like cutaneous changes did not develop until after the introduction of the isotretinoin (Roaccutane). In both cases, withdrawal of the isotretinoin resulted in clinical improvement of their cutaneous signs. The interaction of isotretinoin and another agent, rather than isotretinoin independently, may be involved in the development of pseudoporphyria. PMID- 8440061 TI - Adult onset Mongolian spot. AB - We report a case of adult onset, unilateral, progressive, grey-blue pigmentation on the back of an Asian male. Histology showed the pigmentation to be due to deep dermal melanocytes. The spectrum of clinical presentations of dermal melanocytosis is reviewed and the unique features of this case outlined. PMID- 8440062 TI - Scurvy occurring in a teenager. AB - Scurvy is now an uncommon condition in the western world. We report a case of scurvy in a 14-year-old female with an inadequate diet who developed a purpuric rash affecting her trunk and legs. The rash resolved dramatically with ascorbic acid therapy. PMID- 8440063 TI - Ulcerating necrobiosis lipoidica effectively treated with pentoxifylline. AB - A 30-year-old man had suffered from persistent ulceration within an area of necrobiosis lipoidica diabeticorum for 13 months. The ulcerating necrobiosis lipoidica was resistant to topical therapy and oral therapy with acetylsalicylic acid. However, the ulcers healed completely within 8 weeks of administration of 400 mg pentoxifylline twice daily. PMID- 8440064 TI - Recurrent impetiginized eczema as a presenting manifestation of cyclic neutropenia. AB - A patient is described with a persistent, impetiginized dermatitis that worsened periodically, which was preceded by neutropenic episodes during which her circulating neutrophil count fell to 500-600/ml. Each episode lasted 24 h and had a 7-11 day periodicity. The importance of this case depends on the frequency and brevity of the neutrophil trough levels that made the dermatitis appear to be continuous. Similar cases may be more common than expected as isolated abnormal leukocyte counts may be disregarded as laboratory artefacts. Dermatologists should be cautious in managing patients with persistent atypical impetigo. PMID- 8440065 TI - Lymphoepithelioma-like carcinoma of the skin. AB - A 70-year-old patient who presented with a mass on the dorsum of his nose of 2 years evolution is reported. Histologically it was formed by dermal nests and cords of atypical epithelial cells surrounded by an intense inflammatory infiltrate composed of lymphocytes and histiocytes of an usual aspect. The lesion was removed, relapsing 2 years later. The ultrastructural and immunohistochemical results are discussed. We compare another six cases of lymphoepithelioma-like carcinoma, reported in the literature. The differential diagnosis with other related conditions is discussed together with its possible adnexal origin. PMID- 8440066 TI - 'Fade out' photochromonychia. AB - Two English women are described who developed chestnut-brown pigmentation of the distal part of the finger- and thumb-nail plates whilst using 'over the counter' topical hydroquinone depigmenting creams. In both individuals there was marked deepening of the pigmentation during periods of intense sun exposure. Withdrawal or protection of the nails from the hydroquinone resulted in resolution of the pigmentation. Hydroquinone staining of the nails is not well recognized and this report confirms a previous suggestion of a relationship between the intensity of the pigmentation and light exposure. PMID- 8440067 TI - Epidermodysplasia verruciformis and malignant thymoma. AB - We describe a patient with a long history of skin lesions clinically and histologically consistent with epidermodysplasia verruciformis (EV) who developed malignant thymoma. HPV-9DNA was found in the macular lesion and HPV-4DNA and HPV 9DNA in the coexistent common warts. Thrombocytopenia and hypogammaglobulinaemia preceded the diagnosis of thymoma. Our patient seems to represent an example of an EV-like syndrome in immunodeficiency. PMID- 8440068 TI - An unusual distribution of an acneiform rash due to herpes zoster infection. AB - Acne can affect unusual sites and occur at unusual ages with little involvement of the commonly affected sites. Discrete areas can be affected by acne which has been reported to occur in a naevoid form. We report a patient who developed an acneiform rash in the site of a previous herpes zoster infection. PMID- 8440069 TI - Pili torti with congenital deafness (Bjornstad's syndrome)--report of three cases in one family, suggesting autosomal dominant transmission. AB - Pili torti is a rare hair shaft abnormality in which the hair is flattened and intervals twisted at irregular through 180 degrees about its axis. Pili torti may occur as a congenital defect or as an acquired disorder (secondary to patchy alopecia from a variety of causes). When it is congenital, it may be isolated and determined by an autosomal dominant gene or associated with various rare syndromes, including ectodermal dysplasias, neurological defects and metabolic disturbances. The association of neurosensory hearing loss and pili torti has been recognized as Bjornstad's syndrome since 1965. As far as we know, only 15 cases of this syndrome have been reported. We describe here three cases of Bjornstad's syndrome in one family. PMID- 8440070 TI - Role of late complement components in experimental autoimmune thyroiditis. AB - Availability of a line of rabbits deficient in the sixth complement component (C6 D) made it possible to evaluate the role of the terminal complement complex (TCC) in the development of experimental autoimmune thyroiditis (EAT) of the rabbit. Immunization with saline extract of homologous thyroid, known to be composed predominantly of thyroglobulin, led in normocomplementemic (NC) rabbits to severe thyroiditis, with cellular infiltrates occupying 50-95% of the thyroid, and to minimal or moderate thyroiditis, with 1-35% of thyroids infiltrated in C6-D rabbits. Cellular infiltrates consisted predominantly of mononuclear cells with appreciable numbers of granulocytes. Destruction of thyroid follicles was extensive and diffuse in NC rabbits, but it was only minimal and focal in C6-D rabbits. Immunohistology revealed in both groups of rabbits deposits of IgG and C3 along follicular basal laminae. In addition, NC rabbits showed deposition of C6 and MAC in thyroid follicles. These results suggested that TCC is necessary for the development of fully expressed, severe EAT; simultaneously, however, they showed that a significantly reduced EAT can develop without TCC. Administration of NC but not of C6-D rabbit serum to C6-D rabbits resulted in a significant increase in the severity of EAT. It was also shown that C6-D rabbits have "normal" T-cell activity, since they developed experimental autoallergic encephalomyelitis as readily as NC rabbits. Therefore, it is likely that development of EAT is indeed impaired by the C6 deficiency in rabbits. The requirement for TCC observed in this study may be relevant to the understanding of the pathogenesis of Hashimoto's thyroiditis, in which thyroid tissue was recently shown to contain TCC deposits. PMID- 8440071 TI - Rheumatoid factor isotypes in serum and salivary fluid of patients with primary Sjogren's syndrome. AB - Salivary fluid and serum levels of immunoglobulin and rheumatoid factor (RF) isotypes were measured in patients with primary Sjogren's syndrome (SS) as well as in patients suspected of the syndrome in whom the diagnosis could be excluded (NON-SS) in order to investigate the site of RF production in primary SS and to determine the diagnostic value of determination of salivary fluid levels of RF. Increased salivary fluid levels of IgA-RF were found in 46% of 39 primary SS patients, 14% of 42 NON-SS patients, and in 2% of 41 healthy controls. Salivary fluid levels of other RF isotypes were not increased in the patient groups. The frequency of elevated titers of IgA-, IgG-, and IgM-RF in serum of primary SS patients was 51, 7, and 59%, respectively. The levels of IgA, IgG, and IgM in salivary fluid of primary SS patients were increased in 36, 31, and 23%, respectively. Comparison of RF levels in samples of serum and saliva from primary SS patients after correction for immunoglobulin levels indicated local production of IgA-RF in salivary glands. Significant positive correlations were found between IgA-RF levels in serum and saliva but not between the levels of immunoglobulin isotypes in the two compartments. The results of this study show that (1) increased levels of IgA-, but not IgG- and IgM-RF occur in saliva of primary SS patients; (2) IgA-RF is locally produced in the salivary glands; (3) the stimuli for IgA-RF production in the systemic and secretory compartment may be similar; and (4) measurement of both IgA- and IgM-RF in serum may be used as adjunctive diagnostic procedure for primary SS. PMID- 8440072 TI - Regulation of B cell function by bucillamine, a novel disease-modifying antirheumatic drug. AB - Bucillamine [N-(2-mercapto-2-methylpropionyl)-L-cysteine] (BUC) is a thiol compound that differs from D-penicillamine (DPC) in that it contains two free sulfhydryl groups. Clinical trials have demonstrated that its efficacy in rheumatoid arthritis is superior to that of DPC, but its mechanism of action remains unclear. We therefore examined the effects of BUC on the in vitro function of human B cells in comparison to those of DPC. IgM production was induced from highly purified B cells from healthy donors by stimulation with Staphylococcus aureus Cowan I (SA) plus factors generated from mitogen-activated T cells (TF) or interleukin-2 (IL-2) or with immobilized anti-CD3-activated CD4+ T cells. BUC suppressed the production of IgM at concentrations of 0.3-100 micrograms/ml irrespective of the presence of CuSO4. Whereas BUC suppressed the production of IL-2 and interferon-gamma by immobilized anti-CD3-activated CD4+ T cells, its suppressive effects on the production of IgM in anti-CD3-stimulated cultures were not overcome by addition of TF or IL-2, indicating that the action of BUC involves direct inhibition of B cell function. BUC suppressed the initial stages of B cell activation, but not the maturation of previously activated B cells. In contrast to DPC, the suppressive activities of BUC did not require the presence of copper and were not overcome by the addition of monocytes or catalase. The effects of SA981, a metabolite of BUC with an intramolecular disulfide, on B cell function were more marked than those of BUC, whereas the effects of SA679, another metabolite of BUC with one of the two sulfhydryl bonds methylated, were similar to those of DPC. SA672, a metabolite of BUC with both of the two sulfhydryl bonds methylated, did not suppress B cell function. These results indicate that BUC as well as some of its metabolites inhibit cytokine production by T cells and also suppress the production of IgM at least in part by directly inhibiting B cells. These compounds exert immunosuppressive effects that are similar to those of DPC, but also unique inhibitory effects that depend upon the capacity of BUC to form an intramolecular disulfide between its two sulfhydryl groups. PMID- 8440073 TI - Cytokine mRNA expression in intestine from normal and inflammatory bowel disease patients. AB - Cytokines are involved in the regulation of normal immune events and may be important in the development or perpetuation of immune events in inflammatory bowel disease. We have previously shown that normal human mononuclear cells from tonsil, spleen, and peripheral blood exhibit tissue and stimulus-specific patterns of cytokine mRNA expression. The aim of this study was to determine if disease-dependent differences of cytokine mRNA expression could be found in the intestine. Total RNA was isolated from intestinal mucosa and lamina propria mononuclear cells from inflammatory bowel disease patients and controls. cDNA probes specific for interleukins (IL)-1, -4, -5, and -6 and transforming growth factor-beta were used. IL-1 beta mRNA and TGF-beta mRNA steady state expressions were higher in inflammatory bowel disease specimens than in normal intestine. In addition, mononuclear cell specimens had stronger cytokine mRNA expression than mucosal specimens. The steady state mRNA expression of proinflammatory cytokines is higher in inflammatory bowel disease, consistent with the ongoing inflammation seen. PMID- 8440075 TI - Suppressive effect of interleukin-4 (IL-4) on IL-6 production by adherent rheumatoid synovial cells. AB - Interleukin-6 (IL-6) has recently been characterized as a mediator of multiple inflammatory responses. Excessive production of this cytokine has been demonstrated in the joints of patients with rheumatoid arthritis (RA). On the other hand, anti-inflammatory effects of IL-4 have recently been demonstrated. We therefore investigated the suppressive effect of IL-4 on IL-6 production by synovial cells in patients with RA. Freshly prepared adherent rheumatoid synovial cells expressed IL-6 mRNA and spontaneously produced a large amount of IL-6 in culture. This spontaneous production of IL-6 was significantly suppressed by IL 4. The suppressive effect of IL-4 on IL-6 production was demonstrated in all patients with RA tested in this study. On the other hand, IL-6 mRNA levels already expressed in adherent synovial cells were not reduced by IL-4 in 24 hr of culture. The suppressive effect of IL-4 on IL-6 production suggests that IL-4 is an important physiological regulator of IL-6 production in synovial cells. PMID- 8440074 TI - Subclasses of immunoglobulins and autoantibodies in autoimmune diseases. AB - The differing capacity of subclasses of IgG to bind to protein A and protein G was used in a sequential affinity purification procedure to examine immunoglobulin isotypes and subclasses in autoimmune disease. The utility of the procedure is that affinity-purified fractions containing particular isotypes and subclasses of immunoglobulin can be analyzed for their content of autoantibodies using standard techniques. For each of four autoimmune diseases studied, chronic active hepatitis, Sjogren's syndrome, primary biliary cirrhosis, and rheumatoid arthritis, there were characteristic protein elution profiles and the various disease-specific autoantibodies showed preferential distributions among the isotypes and subclasses. Moreover there was not an absolute correlation between an increased level of a particular subclass and the occurrence of antibodies of that subclass. The occurrence of highly disease-specific immunoglobulin subclass profiles suggests that the hypergammaglobulinemia associated with autoimmunity cannot be attributed entirely to polyclonal B-cell activation. Rather, there are disease-specific alterations in isotype subclass switching which may reflect different cytokine-dependent influences on autoimmune B cells and their products. PMID- 8440076 TI - Human CD4 modulation in vivo induced by antibody treatment. AB - Clinical improvement after treatment with anti-CD4 antibodies has been documented in patients suffering from rheumatoid arthritis. This observation has stimulated the interest in effects induced by the in vivo application of anti-CD4 antibodies. Here, we have investigated features of CD4 modulation during and after anti-CD4 therapy with the monoclonal anti-body MAX.16H5. Depletion of circulating helper T cells was accompanied by modulation of the CD4 molecule down to 30% of the initial antigen density 1 hr after antibody infusion. However, despite the reappearance of CD4+ cells in the circulation CD4 remained down modulated for up to 28 days without a significant residual anti-CD4 binding. Depletion of CD4+ cells as well as CD4 modulation were observed to a similar extent both in responders and non-responders to anti-CD4 therapy. Modulation of CD4 was more effective in vivo than in vitro with a mean reduction of CD4 density down to 46% in vitro. It was induced in varying degrees by all anti-CD4 antibodies investigated except for OKT4 and required viable monocytes in the case of MAX.16H5 and most of the anti-CD4 antibodies investigated. Supernatants from LPS-activated monocytes or the addition of monocytes that were freeze-fractioned or fixed monocytes did not substitute for this requirement. The effect was Fc receptor dependent since F(ab)2 fragments of MAX.16H5 did not induce CD4 modulation. No significant co-modulation was found for a variety of T-cell surface antigens including CD2, CD3, CD8, CD45R, CD45RO, CD25, CDw29, and HLA-DR. In order to test functional effects, the influence of CD4 modulation on the increase of free cytosolic Ca2+ concentration ([Ca2+]i) stimulated via the T-cell receptor complex by an anti-CD3 antibody was studied. A significant inhibition was observed upon direct binding of anti-CD4 to its ligand. However, a diminished CD4 density alone as induced by in vivo modulation did not reduce, but rather enhanced the T cell receptor-mediated mobilization of [Ca2+]i in T cells of the patients. Taken together, no evidence was found that CD4 modulation per se could explain the beneficial effects of anti-CD4 therapy. PMID- 8440077 TI - An infant with macrocephaly, abnormal neuronal migration and persistent olfactory ventricles. AB - An asphyxiated male infant was delivered by cesarean section at 38 weeks gestation. The patient was macrocephalic with clinical evidence of fetal immobility syndrome. He died aged two days. Autopsy revealed excessive brain weight, pachygyria, enlarged olfactory tracts and hypoplastic optic nerves. Microscopy revealed evidence of impaired neuronal migration throughout the cortex. The olfactory bulbs showed persistence of the primitive olfactory ventricles and absence of olfactory glomeruli. There was persistence of the fetal connection between lateral and olfactory ventricles. The lateral geniculate nuclei, inferior olivary nuclei and dentate nuclei of the cerebellum were abnormally formed. Relevant aspects of fetal brain development and clinical neuropathologic syndromes are discussed. PMID- 8440078 TI - Juvenile parkinsonism caused by chronic meningoencephalitis: a clinicopathological study. AB - After a six-year history of poor concentration, intellectual and growth retardation, and a one-year history of absences, an 11-year-old girl developed parkinsonism and thereafter had a progressive, predominantly extrapyramidal disorder for the next nine years, until her death at age 20. Other clinical features included pyramidal signs, peripheral neuropathy and sideroblastic anemia. Despite a clinical course suggestive of a degenerative condition, the principal findings on examination of the brain were chronic meningitis, brainstem encephalitis and mild diffuse cerebral gliosis. Extensive investigations failed to demonstrate an infective agent, either in life or by post mortem examination. PMID- 8440079 TI - Distribution of thrombotic lesions in the cerebral arteries in spontaneous occlusion of the circle of Willis: cerebrovascular moyamoya disease. AB - In this paper, we have attempted to discuss the role of thrombogenesis in the formation or progression of the obstructive vascular lesions in so-called "spontaneous occlusion of the circle of Willis" (cerebrovascular Moyamoya disease) through histopathological observation on the cerebral arteries in this disease. Using the autopsy cases with this disease (28 cases), we examined the histological details of the cerebral arteries, including the circle of Willis and its major branches, to describe the distribution and the nature of thrombotic lesions. Thrombotic lesions were observed in up to 15 out of the 28 cases (54%). Predominant sites of the thrombi were the internal carotid arteries, the posterior communicating arteries, and the posterior cerebral arteries. The high incidence of thrombi formation as well as their distribution which closely correlated with the progression of the intimal lesion of this disease strongly suggested the importance of abnormal thrombogenesis as an etiologic factor in this disease. PMID- 8440080 TI - Calbindin D-28k immunoreactivity in the temporal neocortex in patients with Alzheimer's disease. AB - Calbindin D-28k immunoreactivity in the temporal isocortex was examined in seven patients with Alzheimer's disease (AD) and in six controls. In normal brains, calbindin D-28k-immunoreactive cells were bitufted neurons, multipolar cells with ascending dendrites and large double-bouquet cells mainly located in layers II and III. Immunoreactive fibres were seen in the molecular layer and in vertical bundles in layers III and V/VI. Calbindin D-28k immunoreactivity was reduced in patients with AD, although with differences from one patient to another. Immunoreactivity was decreased in the plexus of the molecular layer and in the vertical bundles in the cellular layers in every case. Most patients had, also, decreased immunoreactivity in the dendritic arbors. The number of calbindin D-28k immunoreactive cells was significantly decreased in three of five patients with moderate or severe dementia, and was normal in two cases with mild dementia. PMID- 8440081 TI - Primary leptomeningeal T-cell lymphoma: a case and a review of primary T-cell lymphoma of the central nervous system. AB - A case of primary leptomeningeal T-cell lymphoma of pleomorphic large cell type is presented. The lymphoma, which was first diagnosed at autopsy, occurred in a 67-year-old man, who had no personal or family history of immunodeficiency disorders. Review of the literature reveals only 13 immunocytochemically well documented cases of primary T-cell lymphoma in the CNS. In five of these cases the lymphoma was apparently confined to the leptomeninges. The relatively high frequency of leptomeningeal presentation may indicate that this tumor form is more common with primary T-cell lymphoma of the CNS than with B-cell neoplasms. PMID- 8440082 TI - Principles of paramunization. Option and limits in veterinary medicine. AB - The so-called primitive immune system has not changed during evolution. Even in primates it plays the most important role in first line defence against invading microorganisms. Cellular components such as macrophages, granulocytes, Natural Killer cells and gamma delta-T cells and soluble humoral factors--the cytokines- are the representatives of the primitive immune system. An interlocking communicative network regulates flexible response of effector cells towards "non self" antigens. It also ensures close connection with the repertoire of specific immune response, e.g. antibody formation. Multifactorial diseases, nosocomial infections, tumour diseases and various forms of immuno-suppression initiated alternative methods in immunotherapy. Immunostimulation at the non-specific defense level has first been noticed as "side effects" of vaccination. Today it should be differentiated between substitution of the immune system with cytokines and induction of the non-specific defense repertoire mimicking natural antigen contact that is called paramunization. Advantages and disadvantages of both methods are discussed. In vitro as well as in vivo experiments with poxviruses document safety and efficacy of purified and inactivated virus particles in paramunization protocols. The main stimulative components of the poxvirus particles are located in the envelope of the virions. Poxvirus-induced stimulation of non-specific defense reactions is likely to have remote effects on the quality of further antigen processing. Besides the induction of a high short term alertness in the primitive immune system paramunization may efficiently influence ongoing specific responses, e.g. immunoglobulin isotype selection. Therefore the term paramunization should not be used to characterize a separate part of the immune system, however, for didactic reasons it will facilitate the understanding of principles of the immune system. PMID- 8440083 TI - The modern epidemiological aspects of rabies in the world. AB - The most recent advances in rabies epidemiology in various wildlife and domestic reservoirs are presented, especially in foxes, bats and dogs. Rabies epidemiology in the dog reservoir is directly associated to dog ecology which needs to be better understood in order to implement appropriate rabies control measures in the dog population. The progress of molecular biology, especially the development of the Polymerase Chain Reaction technique offers many interesting possibilities in epidemiological investigations. PMID- 8440084 TI - Effect of physical exercise on the phagocytic function of peritoneal macrophages from Swiss mice. AB - The influence of strenuous physical exercise (swimming until exhaustion) or physical training (swimming 90 min daily during 20 days) on different aspects of phagocytic function of peritoneal macrophages from Swiss mice was studied. The adherence capacity was not modified by strenuous or training exercise. The spontaneous mobility, chemotaxis, spontaneous attachment and ingestion of Candida albicans and of inert particles (latex beads) were also not modified by the strenuous physical activity, but increased significantly with training. The attachment and ingestion of opsonized C. albicans, as well as the nitroblue tetrazolium (NBT) reduction in the absence (oxidative metabolism measure) or presence (microbicidal capacity measure) of ingested material (C. albicans with and without serum or latex beads), were increased by both the strenuous and the training physical exercises. Moreover, significantly higher values were found for training activity compared with those found for strenuous physical exercise. The advantageous effects of physical exercise in the phagocytic function of macrophages are discussed. PMID- 8440085 TI - In vitro effect of cefoxitin on phagocytic function and antibody-dependent cellular cytotoxicity in human neutrophils. AB - The effects in vitro of Cefoxitin, a beta-lactam antibiotic, at a concentration of 50 micrograms/ml (similar to a therapeutic level in plasma) on each step of the phagocytic process, in addition to antibody-dependent cellular cytotoxicity (ADCC) of blood peripheral human neutrophils have been studied. The antibiotic produced a significant stimulation of adherence capacity, chemotaxis, attachment of Candida albicans to neutrophils and phagocytosis of Candida albicans (with serum, decomplemented serum or without serum), ingestion of inert particles (latex beads), microbicidal activity, and digestion capacity of the ingested material [measured by nitroblue tetrazolium (NBT) reduction]. Moreover, cefoxitin (50 micrograms/ml) demonstrated chemoattractant activity for neutrophils. ADCC was also increased by this antimicrobial agent. These results therefore suggest that a therapeutic concentration of cefoxitin may enhance microbicidal and cytotoxic functions of a pivotal human phagocytic cell: the neutrophil. PMID- 8440086 TI - Incidence of Aeromonas species in diarrhoeic stool in University College Hospital Ibadan, Nigeria. AB - Between February and July 1989, stool samples from 100 diarrhoeic patients were screened for Aeromonas species. For isolation, alkaline peptone water was used for enrichment and xylose desoxycholate citrate agar as differential and selective medium. Only one sample (1%) yielded Aeromonas hydrophila having come from a 2-month old baby. No other enteric pathogens were isolated from the positive stool sample, a strong indication that A. hydrophila was responsible for the diarrhoea in the baby. Of nine antimicrobial agents used the lone A. hydrophila isolate was resistant only to ampicillin. PMID- 8440087 TI - The development of Pneumocystis carinii pneumonia in germ-free rats requires immunosuppression and exposure to the Pneumocystis carinii organism. AB - Adult germ-free rats treated with dexamethasone and exposed to a non-sterile environment did not harbor or develop Pneumocystis carinii cysts or trophozoites after 10 weeks of immunosuppression. Only when they were exposed to infected, conventional rats and treated with dexamethasone for 8 weeks or longer, did adult germ-free rats develop P. carinii infection. PMID- 8440088 TI - Characterization of Pasteurella from gingival scrapings of dogs and cats. AB - Gingival scrapings of 62 dogs and cats were examined for the presence of Pasteurella. Isolation was performed in a medium supplemented with thiostrepton. Twenty-eight and 37 strains were obtained from 21 dogs and 26 cats, respectively, and classified in recently described species or subspecies of the genus Pasteurella (P.): P. multocida subspecies multocida and septica, P. canis, P. dagmatis and P. stomatis. Twenty-one strains were classified as atypical P. stomatis and one strain obtained from a cat remained unclassified. All strains were susceptible to the antibiotics studied. P. multocida and P. stomatis (including atypical strains) represented 65 and 30% of feline isolates, and 14 and 68% of canine isolates, respectively. Assuming that P. multocida, P. canis and P. dagmatis are potentially pathogenic for humans, and that P. stomatis has a low pathogenicity or non-pathogenic, 77 and 28% of examined cats and dogs harboured one or several pathogenic strains. This difference could explain the fact that Pasteurella infections in man are lower in dog bites rather than cat bites. PMID- 8440089 TI - The isolation of cytotoxic necrotizing factor (CNF)-producing Escherichia coli from the intestinal contents of babies who died of sudden infant death syndrome (SIDS) and other causes as well as from the faeces of healthy babies. AB - Strains of Escherichia coli producing cytotoxic necrotizing factor (CNF) have been isolated from intestinal contents of 16.8% of babies who died of Sudden Infant Death Syndrome (SIDS) and 16.5% of faeces from healthy babies. While no difference in CNF carriage was seen, it is noteworthy that these CNF-producing E. coli are present in such specimens. Some of the CNF-producing E. coli belonged to serotypes associated with this factor in other parts of the world. PMID- 8440090 TI - Detection of tumor necrosis factor activity in the supernatants of feline macrophages and lymphocytes. AB - Using tumor necrosis factor (TNF)-sensitive L929 cells, TNF-like activity was assayed in the supernatants of feline macrophage and lymphocyte cultures. Macrophages were separated from thioglycollate-elicited peritoneal cells. Lymphocytes were purified from peripheral blood and were then stimulated with calcium ionophore A23187 and phorbol myristate acetate. Lymphocyte stimulators alone did not have cytotoxicity against L929 cells. Based on the facts that cytotoxicity decreased with increasing dilutions of supernatant and that this cytotoxic activity could be blocked by antibody to human TNF, the activity detected in the supernatants of the feline macrophages and lymphocytes was likely due to feline TNF-alpha or -beta. PMID- 8440091 TI - Suspended judgment n-of-1 trials. PMID- 8440092 TI - Exact repeated confidence intervals for Bernoulli parameters in a group sequential clinical trial. AB - This paper presents methods for constructing exact repeated confidence intervals (RCIs) for the success probability, p, of a single Bernoulli treatment and for the difference of success probabilities, delta = p1-p2, of two independent Bernoulli treatments in the context of a group sequential clinical trial. These RCIs calculated at each interim analysis are useful for evaluating the data in light of all the information available rather than relying on rigid stopping criteria used by repeated significance tests. Extensions to construction of RCIs for the relative risk p = p1/p2 and odds ratio psi = p1(1-p2)/p2(1-p1) are indicated. PMID- 8440093 TI - Operational and policy considerations of data monitoring in clinical trials: the Diabetes Control and Complications Trial experience. AB - Many clinical trials incorporate a system for monitoring emerging data that utilizes a committee composed of individuals who are independent of the investigators conducting the study. Although this is a common practice, there is a paucity of publications examining the operating methods of these groups. This paper describes the composition, functions, and procedures of the Data, Safety and Quality Review Group (DSQ) of the Diabetes Control and Complications Trial (DCCT). The DSQ is not masked to emerging data and the voting membership is made up of individuals with a wide diversity of expertise that reflects the needs of the trial. There are also nonvoting exofficio members who represent other components of the study organization. In addition to data monitoring, the DSQ provides external review of coordinating center operations. A distinctive aspect of the DCCT's DSQ is the creation of a free-standing operations manual for the DSQ's use during the trial and the involvement of the study investigators in developing certain sections of this document. Utilizing a process that allowed participation of the investigators was considered critical to achieving a mutual understanding regarding the planned uses and interpretations of the study data prior to the study's completion so as to minimize the chances of major disagreements regarding the conclusions drawn. Equally important, the existence of such a manual provides documentable reassurance to all interested parties that both scientific integrity and patient safety are being closely watched and gives the study investigators confidence that the results of the study will be scientifically credible and clinically important. PMID- 8440094 TI - Design features of a controlled clinical trial to assess the effect of an HMG CoA reductase inhibitor on the progression of coronary artery disease. Canadian Coronary Atherosclerosis Intervention Trial Investigators Montreal, Ottawa, and Toronto, Canada. AB - This report describes the design and methodological features of a double-masked, randomized, placebo-controlled trial to determine whether administration of the HMG CoA reductase inhibitor lovastatin retards the progression or facilitates the regression of coronary atherosclerosis. The study population consists of coronary patients with a recent arteriogram that characterizes them as being at high risk for coronary progression and a baseline fasting total serum cholesterol > or = 5.7 mmol/L and < or = 7.8 mmol/L. Lovastatin, or matching placebo, are up titrated from 20 mg to 40 mg to 80 mg/day during the first 16 weeks of the study in an attempt to attain a fasting serum LDL cholesterol level of 3.4 mmol/L; patients and study personnel remain masked as to cholesterol levels throughout the trial. Coronary arteriography is repeated at 2 years, or earlier if necessitated by worsening symptoms, and all segments are measured quantitatively using a computer-based system. The primary outcome of the trial is a comparison between the lovastatin and placebo groups for coronary change score, defined as the mean of the minimum lumen diameter changes for all lesions (follow-up minus baseline arteriogram) per patient. The advantages and limitations of coronary arteriographic trials and some of the issues related to outcome measurements are discussed. The question posed by this study is of clinical relevance because the consequences of progression of coronary disease, angina, myocardial infarction, and sudden cardiac death are leading causes of morbidity and mortality. PMID- 8440095 TI - Monoclonal antibodies to tumor necrosis factor in sepsis: help or harm? PMID- 8440096 TI - Measured and predicted energy expenditure in critically ill patients. PMID- 8440097 TI - Drowning: to treat or not to treat--an unanswerable question? PMID- 8440098 TI - International safety standards in the intensive care unit. PMID- 8440099 TI - Influence of an anti-tumor necrosis factor monoclonal antibody on cytokine levels in patients with sepsis. The CB0006 Sepsis Syndrome Study Group. AB - OBJECTIVES: To determine the safety, pharmacokinetics, and activity of an anti tumor necrosis factor (TNF)-alpha monoclonal antibody in severe sepsis. DESIGN: Open-label, prospective, phase II multicenter trial with escalating doses of a murine monoclonal antibody (CB0006). SETTING: Twelve academic medical center intensive care units in the United States and Europe. PATIENTS: Eighty patients with severe sepsis or septic shock who received standard supportive care and antimicrobial therapy in addition to the anti-TNF antibody. INTERVENTIONS: Patients were treated intravenously with one of four dosing regimens with CB0006: 0.1 mg/kg, 1.0 mg/kg, 10 mg/kg or two doses of 1 mg/kg 24 hrs apart. MEASUREMENTS AND MAIN RESULTS: The murine monoclonal anti-TNF antibody was well tolerated despite the development of anti-murine antibodies in 98% of patients. No survival benefit was found for the total study population, but patients with increased circulating TNF concentrations at study entry appeared to benefit by the high dose anti-TNF antibody treatment. Increased interleukin (IL)-6 levels predicted a fatal outcome (p = .003), but TNF levels were not found to be a prognostic indicator. TNF levels were higher (206.7 +/- 60.7 vs. 85.9 +/- 26.1 pg/mL; p < .001) and outcome was poor (41% vs. 71% survival; p = .007) in patients who were in shock at study entry when compared with septic patients not in shock. CONCLUSIONS: The murine anti-TNF-alpha monoclonal antibody CB0006 has proven to be safe in this clinical trial and may prove to be useful in septic patients with increased circulating TNF concentrations. Further studies are needed to determine efficacy and the ultimate clinical utility of this immunotherapeutic agent in sepsis. PMID- 8440100 TI - Improved cardiovascular stability during continuous modes of renal replacement therapy in critically ill patients with acute hepatic and renal failure. AB - OBJECTIVE: To determine whether continuous modes of renal replacement therapy result in improved cardiovascular stability compared with standard daily intermittent treatment in critically ill patients. DESIGN: Prospective, randomized controlled trial. SETTING: Intensive care unit in a quaternary referral center for liver failure/transplantation. PATIENTS: Thirty-two consecutive, critically ill, mechanically ventilated patients with combined acute hepatic and renal failure. INTERVENTIONS: Patients were randomized to treatment with either intermittent machine hemofiltration or continuous modes of renal replacement therapy; continuous arteriovenous hemofiltration (CAVH) or arteriovenous hemofiltration with dialysis (CAVHD), provided intracranial pressure was controlled. MEASUREMENTS AND MAIN RESULTS: Cardiac output, tissue oxygen delivery (DO2), and uptake were assessed during 32 treatments with intermittent machine hemofiltration (4 hrs) and during the first 5 hrs of 25 continuous treatments (CAVH and CAVHD). During the first hour of treatment, there was a reduction in cardiac index of 15 +/- 2% during intermittent machine hemofiltration compared with no significant change during the continuous modes of treatment (CAVH/CAVHD) (3 +/- 3%; p < .05). This reduction in cardiac output during intermittent machine hemofiltration was associated with a maximum reduction in mean arterial pressure from 82 +/- 2 to 66 +/- 2 mm Hg (p < .001), a reduction in pulmonary artery occlusion pressure of 27 +/- 4%, tissue DO2 of 15 +/- 3%, and tissue oxygen uptake of 12 +/- 5%, with no significant change in systemic vascular resistance and an increase in pulmonary vascular resistance of 50 +/- 12%. In addition, there was a maximum increase in intracranial pressure of 45 +/- 5% during the first hour of intermittent machine hemofiltration. There were no significant changes during the same time period during the continuous modes of renal replacement therapy. CONCLUSIONS: In critically ill patients, in whom DO2 is impaired, the use of continuous forms of renal replacement therapy is preferred for its improved cardiovascular tolerance compared with daily intermittent machine treatments. PMID- 8440101 TI - Oral ranitidine as prophylaxis for gastric stress ulcers in intensive care unit patients: serum concentrations and cost comparisons. AB - OBJECTIVES: a) To determine whether enteral ranitidine in intensive care unit (ICU) patients would produce serum levels that would reduce stimulated gastric acid by > or = 50%, and b) to evaluate the differences in cost between enteral and parenteral administration of ranitidine. DESIGN: Prospective, nonrandomized clinical trial. SETTING: A surgical ICU in a public primary teaching hospital for a medical school. PATIENTS: Postoperative or posttraumatic surgical patients who met one or more main criteria for stress. INTERVENTIONS: Two groups of patients were given ranitidine through a nasogastric tube. Group 1 (n = 10) received 150 mg every 12 hrs, and group 2 (n = 8) received 300 mg every 12 hrs. MEASUREMENTS AND MAIN RESULTS: Serum samples for measurement of ranitidine concentrations were collected at 2, 6, and 12 hrs after the fifth dose of oral ranitidine. Patients were monitored for upper gastrointestinal bleeding. All patients had therapeutic serum ranitidine concentrations at 2 and 6 hrs, while 88% of patients had therapeutic levels at 12 hrs. CONCLUSIONS: a) Enteral administration of ranitidine every 12 hrs leads to effective absorption of the drug from the upper gastrointestinal tract of ICU patients. b) Serum concentrations of ranitidine for both 150-mg and 300-mg enteral doses remained within, or exceeded, the therapeutic range in > 90% of ICU patients with clinically important criteria of stress. PMID- 8440102 TI - Atrial natriuretic peptide release in response to different positive end expiratory pressure levels. AB - OBJECTIVE: To assess the influence of different positive end-expiratory pressure (PEEP) levels on plasma atrial natriuretic peptide concentrations. DESIGN: Prospective, randomized study. SETTING: Intensive care unit of a university hospital. PATIENTS: Twenty-seven patients who were mechanically ventilated due to acute respiratory failure. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The patients were randomized into three groups: in each group, a defined PEEP level (5, 10, or 15 cm H2O, respectively) was applied, alternating with zero PEEP (0 cm H2O) in consecutive order (reversal experiment). Blood samples for the determination of atrial natriuretic peptide concentrations were drawn from the pulmonary artery and the radial artery catheters. There were no decreases in atrial natriuretic peptide concentrations with a PEEP of 5 cm H2O, but significant decreases could be shown for PEEP values of 10 and 15 cm H2O. The patients of all groups were subjected to PEEP levels of 5, 10, 15, and 20 cm H2O in randomized order (step experiment). The data demonstrated a significant inverse correlation between changes in PEEP levels and changes in plasma atrial natriuretic peptide concentrations. CONCLUSION: The data suggest that the release of atrial natriuretic peptide is influenced by a PEEP of > or = 10 cm H2O, while a PEEP of < or = 5 cm H2O does not disturb this cardiac endocrine function. PMID- 8440103 TI - Interaction between intrinsic positive end-expiratory pressure and externally applied positive end-expiratory pressure during controlled mechanical ventilation. AB - OBJECTIVE: To assess the interaction between intrinsic and externally applied positive end-expiratory pressure (intrinsic PEEP and administered PEEP) in mechanically ventilated patients. DESIGN: Prospective study. SETTING: Intensive care unit of a university hospital. PATIENTS: Twelve consecutive critically ill patients. INTERVENTIONS: Application of an external PEEP of the same value as the intrinsic PEEP. MEASUREMENTS AND MAIN RESULTS: We found that when the administered PEEP was increased from 0 to the baseline value of intrinsic PEEP, mean intrinsic PEEP decreased from 6.5 +/- 4.2 (SD) to 1.3 +/- 0.7 cm H2O (p = .001). The mean end-inspiratory pressure was increased from 20.3 +/- 4.6 to 23.1 +/- 6.1 cm H2O (p < .05). The difference between the modification of intrinsic PEEP and the change in the end-inspiratory pressure was not significantly > 0 cm H2O. Thus, the increase in end-inspiratory pressure may be directly attributable to the increase in total PEEP (administered PEEP plus intrinsic PEEP). None of the other measurements of pulmonary mechanics changed (peak pressure, inspiratory resistance, compliance, and trapped-gas volume). CONCLUSIONS: The administration of positive end-expiratory pressure equal to the intrinsic positive end expiratory pressure causes the almost total disappearance of the intrinsic positive end-expiratory pressure. When the administered positive end-expiratory pressure does not exceed the intrinsic positive end-expiratory pressure, the former is applied almost in its entirety to the patient's external circuit. The administration of positive end-expiratory pressure without prior quantification of the intrinsic positive end-expiratory pressure results in an overestimation of the beneficial effects of the administered positive end-expiratory pressure on the quasi-static compliance. PMID- 8440104 TI - Comparison of mask and nasal continuous positive airway pressure after extubation and mechanical ventilation. AB - OBJECTIVE: To examine the effects of continuous positive airway pressure applied via face masks and nose masks on the change in functional residual capacity and gas exchange. DESIGN: Descriptive and prospective study. SETTING: Intensive care unit of a university hospital. PATIENTS: Ten patients with acute lung injury who had required mechanical ventilation. INTERVENTIONS: Continuous positive airway pressure at a level of 10 cm H2O applied in random order via face and nose masks. MEASUREMENTS AND MAIN RESULTS: Both continuous positive airway pressure methods resulted in an almost identical increase of functional residual capacity. During nasal continuous positive airway pressure, the increase in functional residual capacity was 294 +/- 82 mL. During mask continuous positive airway pressure, the increase in functional residual capacity was 290 +/- 85 mL. PaO2 increased and the alveolar-arterial oxygen tension/alveolar oxygen tension quotient decreased significantly during mask continuous positive airway pressure and nasal continuous positive airway pressure at a level of 10 cm H2O. Two patients showed a periodic change in their breathing patterns; they took a few breaths at an increased lung volume, followed by one deep expiration caused by mouth opening. Change in mask pressure was negligible in these two patients. Using a visual analog scale (10 = highly comfortable; 0 = severely uncomfortable), the patients rated nasal continuous positive airway pressure (8.6 +/- 0.9) significantly more comfortable than mask continuous positive airway pressure (2.6 +/- 0.8). CONCLUSION: The major advantages of continuous positive airway pressure (the improvement of functional residual capacity and oxygen transfer) can also be achieved with nasal continuous positive airway pressure in the postextubation period in patients who have been mechanically ventilated for acute lung injury. PMID- 8440105 TI - The Acute Physiology and Chronic Health Evaluation II classification system is a valid marker for physiologic stress in the critically ill patient. AB - OBJECTIVE: To compare the Acute Physiology and Chronic Health Evaluation (APACHE II) score with resting energy expenditure obtained from indirect calorimetry to determine whether the APACHE II scoring system is an accurate, objective measure of the degree of critical illness and physiologic stress between groups of patients. DESIGN: Prospective study. SETTING: University hospital, tertiary referral center. PATIENTS: Seventy critically ill patients, consecutively sampled from burn, surgical, and medical intensive care units. INTERVENTIONS: Indirect calorimetric studies were performed on each patient using a metabolic cart. The acute physiologic score component of the APACHE II scoring system was determined at the time of metabolic testing, a mean of 15.9 days after hospital admission. MEASUREMENTS AND MAIN RESULTS: True resting energy expenditure was calculated by adjusting the measured energy expenditure for diet-induced thermogenesis and fever. A predicted resting energy expenditure was calculated for each patient using the Harris-Benedict equation alone, and by using the Harris-Benedict value corrected for previously published metabolic activity factors. To eliminate differences in body composition and size, true resting energy expenditure was divided by weight, body surface area, and Harris-Benedict resting energy expenditure. Results showed no significant correlation between APACHE II scores and either the Harris-Benedict resting energy expenditure or the Harris-Benedict value corrected by metabolic activity factors. However, there was a significant (p < or = .001; r2 = .18 to .20) relationship between increasing APACHE II scores and both increasing measured and true resting energy expenditure. The true resting energy expenditure divided by body surface area, kilogram body weight, and Harris-Benedict predicted value, were all shown to be significantly (p < .01) related to APACHE II score, but showed no better degree of correlation (r2 = .12 to .23) than comparison of APACHE II score with measured or true resting energy expenditure. CONCLUSIONS: The APACHE II classification may be a valid marker of physiologic stress as demonstrated by its statistically significant (although weak) relationship with indirect calorimetric measures of energy expenditure associated with varying degrees of critical illness. PMID- 8440106 TI - Near drowning: is emergency department cardiopulmonary resuscitation or intensive care unit cerebral resuscitation indicated? AB - OBJECTIVES: a) To report the neurologic outcome of a series of near-drowning victims treated with supportive management without aggressive cerebral resuscitation; and b) to identify patient characteristics that indicate prognosis and guide therapy at the scene, the Emergency Department, and in the intensive care unit (ICU). DESIGN: Retrospective review of all near-drowning patients requiring admission to the ICU over a 6-yr period (1/1/82 to 12/31/88). Hospital records were examined for the circumstances of submersion and rescue, patient condition on arrival in the Emergency Department and ICU, treatments, hospital course, and ultimate outcome. SETTING: Emergency departments of the referring hospital and ICU of Children's Hospital. PATIENTS: Forty-four pediatric submersion victims were treated with therapy limited to the support of vital functions. Three patients who met cold-water drowning criteria were excluded from the analysis for predictors of neurologic outcome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In our warm-water near-drowning patients, 56% survived neurologically intact, 32% survived in a persistent vegetative state, and the remaining 32% died. Unreactive pupils in the Emergency Department and a Glasgow Coma Score of < or = 5 on arrival to the ICU were the best independent predictors of poor neurologic outcome (odds ratio and 95% confidence intervals 374 [17 to 16,000] and 51 [5 to 2,200], respectively). However, no predictor was absolute and two nonhypothermic patients who arrived to the Emergency Department without vital signs, requiring cardiopulmonary resuscitation and cardiotonic medications, had full neurologic recovery. CONCLUSIONS: Our results cast further doubt on the utility of aggressive forms of cerebral monitoring and resuscitation and emphasize the need for initial full resuscitation in the Emergency Department. PMID- 8440107 TI - Time-consuming procedures and prehospital thrombolytic treatment. AB - OBJECTIVES: To assess time-consuming procedures in the prehospital stage of acute myocardial infarction patients who had received thrombolytic therapy at the scene, and to evaluate their effect on the clinical outcome. DESIGN: Prospective study. SETTING: Mobile intensive care unit staffed by an intern or a hospital based physician. PARTICIPANTS AND INTERVENTIONS. Thrombolytic therapy with recombinant tissue-type plasminogen activator (total dose of 120 mg/6 hrs) was initiated at the scene in 167 patients. Treatment continued during transportation and thereafter in the cardiac care unit. During hospitalization, radionuclide ventriculograms and coronary angiography were performed in most patients. MEASUREMENTS AND MAIN RESULTS: Correct diagnosis was confirmed in 165 of 167 patients. Mean time to treatment was 96 +/- 42 (SD) mins with no significant difference between patients treated at home (n = 105) or in public places (n = 60). Global duration of treatment was significantly shorter when thrombolytic therapy was given in public as compared with treatment applied at home (50 +/- 13 vs. 57 +/- 16 mins, respectively, p < .002). CONCLUSION: If patients and physicians become aware of the potential advantages of prompt initiation of thrombolytic therapy at the scene, critical time may be saved in delivering thrombolysis to the clotted coronary artery. PMID- 8440108 TI - Left ventricular function in patients with acute myocardial infarction, acute pulmonary edema, and mechanical ventilation: relationship to prognosis. AB - OBJECTIVES: To evaluate the relationship between left ventricular function and prognosis in patients treated with mechanical ventilation for severe, persistent pulmonary edema as a consequence of acute myocardial infarction. DESIGN: A prospective study. SETTING: A nine-bed coronary care unit in a 900-bed teaching hospital. PATIENTS: Sixty-nine successive patients. INTERVENTIONS: All patients had acute pulmonary edema not responding to classical treatment and were treated with mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: The inhospital mortality rate was 67%. Thirteen of 23 patients surviving hospitalization died during follow-up, a mean of 5.8 +/- 7.7 months after infarction. Six of ten long term survivors are in functional capacity class 1 or 2 (New York Heart Association) and four survivors are in class 3. Echocardiographic examination indicated that severe left ventricular dysfunction was present in most patients during the time of mechanical ventilation. Repeat echocardiographic examination performed 14.2 +/- 8.1 months after infarction showed a remarkable improvement in left ventricular function among the survivors. Multivariate analysis indicated that the small group of patients with a good long-term prognosis could not be separated prospectively from the larger group dying during or after hospitalization using variables obtained at the time of mechanical ventilation. CONCLUSIONS: The mortality rate is high in this group of patients. Left ventricular function of survivors is severely diminished at the time of infarction but improves markedly during follow-up. The small subgroup of patients with a good long-term prognosis cannot be identified prospectively when evaluated during the acute stage of infarction and the provision of mechanical ventilation. PMID- 8440109 TI - Enteral nutrition with simultaneous gastric decompression in critically ill patients. AB - OBJECTIVE: Early enteral nutrition is an important adjunct in the care of critically ill patients. A double-lumen gastrostomy tube with a duodenal extension has been reported to enable early enteral feeding with simultaneous gastroduodenal decompression. We tested the ability of this device to achieve these goals in critically ill patients. DESIGN: Noncomparative, descriptive case series. SETTING: Surgical intensive care unit in a university hospital. PATIENTS: Fifteen consecutive critically ill patients, who, at the time of laparotomy, were assessed likely to need long-term nutritional support and gastric decompression, underwent tube placement. Mean age was 47 +/- 21 yrs. Mean Acute Physiology and Chronic Health Evaluation (APACHE II) and Therapeutic Intervention Scores were 15 +/- 7.3 (SD) and 29 +/- 10.2, respectively, and the mean Injury Severity Score of 11 trauma patients in the group was 27 +/- 7.4. INTERVENTIONS: Correct tube positioning was verified by radiograph or endoscopy. METHODS: Caloric and protein requirements, nutritional parameters, and problems encountered with the device were recorded. The correlation between the volume of feeding port input and suction port output was noted, and this correlation was considered significant if r2 was > or = .5. RESULTS: Only three (20%) of 15 patients reached full enteral nutritional support via the enteral route. None of these patients achieved this level of nutritional support within the first postoperative week. In 67% of the patients, large quantities of enteral feeding solution appeared in the gastroduodenal suction port effluent. When feeding port input was plotted against effluent volume, a correlation coefficient of > .71 (r2 = > or = .5) was found in 40% of the patients. Other complications included: a) excessive gastroduodenal drainage requiring fluid/electrolyte replacement in eight (53.3%) patients; and b) skin ulceration at the tube entrance site in seven (46.7%) patients. CONCLUSIONS: These data do not support the use of this device for early enteral feeding and simultaneous gastric decompression in critically ill patients. PMID- 8440110 TI - Hypercortisolism in septic shock is not suppressible by dexamethasone infusion. AB - OBJECTIVE: To explore the feedback regulation of glucocorticoids on corticotropin secretion in patients with septic and nonseptic circulatory shock. DESIGN: Prospective study. SETTING: An intensive care unit of a general hospital. PATIENTS: Two groups of patients with septic shock (n = 11) or nonseptic shock (n = 7). A control group (n = 20) was also studied. INTERVENTIONS: Intravenous dexamethasone (1 mg/hr for 4 hrs) suppression test. MEASUREMENTS: Plasma concentrations of corticotropin-releasing factor, beta-lipotropin, and corticosteroid-binding globulin measured by radioimmunoassays, and plasma cortisol measured by radiocompetition assay; the ratio of cortisol to corticosteroid-binding globulin calculated as the free cortisol index. MAIN RESULTS: In both groups of patients, the concentrations of plasma cortisol and beta-lipotropin, and the ratio of cortisol to corticosteroid-binding globulin, were higher than normal subjects (p < .001) and were not different between septic and nonseptic shock patients, whereas the plasma corticosteroid-binding globulin concentration was significantly (p < .001) lower in septic shock patients than in normal subjects (444 +/- 154 vs. 696 +/- 56 nmol/L [22.0 +/- 7.6 vs. 34.5 +/- 2.8 mg/L]), but not significantly lower in nonseptic shock patients (607 +/- 157 nmol/L [30.0 +/- 7.8 mg/L]). In contrast to the complete suppressive effect of dexamethasone infusion on cortisol and beta-lipotropin concentrations in normal subjects, dexamethasone did not suppress cortisol or lipotropin in either septic or nonseptic shock patients. CONCLUSIONS: During circulatory shock, hypercortisolism is associated with high concentrations of lipotropin, and is not suppressible by intravenous dexamethasone infusion. PMID- 8440111 TI - Volume recruitment maneuvers are less deleterious than persistent low lung volumes in the atelectasis-prone rabbit lung during high-frequency oscillation. AB - OBJECTIVES: To test whether the pulmonary risk of repeated volume recruitment is greater or less than the risk associated with unreversed atelectasis during 6 hrs of high-frequency oscillatory ventilation in the atelectasis-prone rabbit lung. DESIGN: Prospective, controlled, randomized comparison over 6 hrs of ventilator management. SETTING: Laboratory. SUBJECTS: Twenty-eight adult New Zealand white male rabbits (weight 2.3 to 2.8 kg). BACKGROUND: Controversy exists over whether high-frequency oscillatory ventilation should be used with volume recruitment maneuvers in the atelectasis-prone lung, or be used at low mean and peak pressures without volume recruitment to avoid the risks of even transient pulmonary overdistention. Potential risks and benefits accompany both alternatives. INTERVENTIONS: We evaluated the pulmonary effects of three high frequency oscillatory ventilation protocols in anesthetized rabbits made surfactant deficient by saline lavage, using animals ventilated with conventional positive-pressure ventilation with positive end-expiratory pressure as a reference group; n = 5 in each group. The three high-frequency oscillatory ventilation groups were ventilated for 6 hrs at 15 Hz (900 breaths/min), FIO2 = 1.0. The repeated stretch group received 15-sec sustained inflations at 30 cm H2O mean airway pressure every 20 mins, with maintenance mean airway pressure sufficient to keep PaO2 > 350 torr (46.7 kPa). The repeated deflation group was maintained at levels that produced PaO2 70 to 120 torr (9.3 to 16 kPa), with the endotracheal tube opened to atmospheric pressure for 15 secs every 20 mins. Animals in the repeated stretch after deflations group were managed as in the repeated stretch protocol but each sustained inflation was preceded by a 15-sec deflation to functional residual capacity. The conventional positive-pressure ventilation group was ventilated at rates of 30 to 100 breaths/min, keeping PaO2 70 to 120 torr (9.3 to 16 kPa). End-points included terminal functional residual capacity and a compliance index computed from respiratory system pressure-volume curves. MEASUREMENTS AND MAIN RESULTS: After 6 hrs of ventilation, respiratory system compliance in the repeated stretch group had returned to control values (1.35 +/- 0.18 [SD] mL/kg/cm H2O). Respiratory system compliance was significantly less than this number in both the repeated deflation (0.89 +/- 0.08) and repeated stretch after deflations (1.24 +/- 0.22) groups (p < .05). Respiratory system compliance after 3 hrs of conventional positive-pressure ventilation decreased to 0.34 +/- 0.10 mL/kg/cm H2O. Functional residual capacity changes paralleled these changes of respiratory system compliance. CONCLUSIONS: These data demonstrate that the potential pulmonary risk of repeated lung stretch during volume recruitment is significantly less than the damage arising from the avoidance of such maneuvers in lungs in which alveolar recruitment is possible. We conclude that sustained inflations during high-frequency oscillatory ventilation produce the benefits of increased oxygenation for a given mean airway pressure plus decreased progression of lung injury. PMID- 8440112 TI - Effects of graded doses of epinephrine on both noninvasive and invasive measures of myocardial perfusion and blood flow during cardiopulmonary resuscitation. AB - OBJECTIVES: Epinephrine administered during cardiopulmonary resuscitation (CPR) is known to increase aortic diastolic and myocardial perfusion pressures, while enhancing myocardial blood flow. Optimal dosing of epinephrine during CPR is less certain. Interest in high-dose epinephrine use under such circumstances is increasing. The effect of different doses of epinephrine on simultaneously measured perfusion pressures, myocardial blood flow, cardiac output, and end tidal CO2 (PCO2) (used as an indirect measure of cardiac output during CPR) is unknown. DESIGN: Prospective, sequential evaluation of no epinephrine, standard dose epinephrine, and high-dose epinephrine. SETTING: An experimental resuscitation laboratory. SUBJECTS: Twelve domestic swine. INTERVENTIONS: Myocardial perfusion pressure, myocardial blood flow, cardiac output, and end tidal PCO2 were studied after various doses of epinephrine were administered during prolonged CPR. After 3 mins of untreated ventricular fibrillation, each animal received 5 mins of CPR without epinephrine, 5 mins of CPR after standard dose epinephrine (0.02 mg/kg), and 5 mins of CPR after high-dose epinephrine (0.2 mg/kg). Cardiac output and regional myocardial blood flow values were measured with nonradioactive, colored microspheres. MEASUREMENTS AND MAIN RESULTS: Myocardial perfusion pressure (aortic diastolic minus right atrial diastolic) was significantly (p < .05) increased over baseline with high-dose epinephrine (35 +/ 8 vs. 14 +/- 4 mm Hg), but not with standard dose epinephrine (20 +/- 5 vs. 14 +/- 4 mm Hg). Epinephrine's effect on myocardial blood flow was similar, increasing after the high dose (71 +/- 21 vs. 20 +/- 5 mL/min/100 g; p > .05), but not with the standard dose (23 +/- 6 vs. 20 +/- 5 mL/min/100 g). Cardiac output decreased significantly (p < .05) after high-dose epinephrine (7 +/- 1 vs. 13 +/- 1 mL/min/kg). Mean end-tidal PCO2 levels were lower after high-dose epinephrine (15 +/- 2 vs. 20 +/- 2 mm Hg; p < .05) but not after standard dose epinephrine (19 +/- 2 vs. 20 +/- 2 mm Hg). CONCLUSIONS: Standard dose epinephrine had minimal effect on myocardial perfusion pressure, myocardial blood flow, cardiac output, or end-tidal PCO2. High-dose epinephrine enhanced myocardial perfusion pressure and myocardial blood flow despite significantly decreasing cardiac output. PMID- 8440113 TI - Cardiovascular effects of dopamine and dobutamine in conscious pigs with chronic heart failure. AB - OBJECTIVE: To test the hypothesis that the cardiovascular responses of dopamine and dobutamine might be affected by the cardiovascular conditions. DESIGN: Prospective, controlled dose-response comparison of dopamine and dobutamine. SETTING: Laboratory for Experimental Cardiology at a university. SUBJECTS: Normal conscious pigs and conscious pigs with chronic left ventricular dysfunction induced by occlusion of a coronary artery 3 to 4 wks before measurements were obtained. INTERVENTIONS: Intravenous infusions of dopamine and dobutamine at rates of 1 to 25 micrograms/kg/min. MEASUREMENTS AND MAIN RESULTS: Left ventricular function was characterized by a lower cardiac output in the pigs with left ventricular dysfunction (23%), stroke volume (34%), and left ventricular pressure (15%), and a higher heart rate (16%), peripheral resistance (41%), and left ventricular end-diastolic pressure (96%) than the normal pigs. Dopamine increased cardiac output to the same extent in the animals with failure as in the normal animals; stroke volume increased only in the animals that had left ventricular dysfunction. The vasodilatory response to dopamine was also similar, but the increase in left ventricular pressure was attenuated similar, in the animals with left ventricular dysfunction, compared with normal animals. Dobutamine showed cardiovascular effects equivalent to dopamine. Left ventricular work, depressed at baseline, increased more rapidly during infusion of dopamine (or dobutamine) in the animals with heart failure than in normal animals. CONCLUSIONS: Both dopamine and dobutamine increased cardiac output in conscious pigs with chronic heart failure. Unlike the response in normal conscious pigs, in which only heart rate increased, in animals with heart failure, these agents enhanced both stroke volume and heart rate. PMID- 8440115 TI - Intensive management and treatment of severe Guillain-Barre syndrome. AB - OBJECTIVE: To review the management and therapeutic approaches to severe acute Guillain-Barre syndrome, with emphasis on the ventilatory dysfunction, and cardiovascular instability seen in patients with this syndrome. DATA SOURCES/STUDY SELECTION: Clinical studies on Guillain-Barre syndrome patients, physiologic studies on animals and humans. DATA EXTRACTION/SYNTHESIS: Guillain Barre syndrome is an acutely evolving, immune-mediated, inflammatory disorder of the peripheral nervous system, leading to demyelination and axonal loss. Clinical hallmarks are symmetric flaccid muscle paresis and areflexia in the presence of an increased cerebrospinal fluid protein content, and electrophysiologic studies demonstrating evolving demyelination. The only well-investigated, efficacious immunomodulatory therapy is plasmapheresis. Plasmapheresis has been shown to decrease ventilator dependence in severe Guillain-Barre syndrome. Ventilatory failure and cardiovascular instability are the main reasons for intensive care support. Ventilatory failure is caused by involvement of airway and respiratory muscles, particularly the diaphragm. Cardiovascular instability is due to involvement of the autonomic nervous system and results in labile blood pressure, cardiac arrhythmias, and hypovolemia. After admission to the intensive care unit, the most serious complications result from mechanical ventilation, circulatory disturbances, thrombosis, starvation, and sepsis. Special emphasis should be given to psychologic support and management of pain. CONCLUSIONS: With modern intensive care support, the outcome is excellent (> 80% recovery). In severe cases, a higher frequency of persistent residual paresis occurs; however, the majority of this group ultimately have a good functional recovery. PMID- 8440114 TI - Effects of norepinephrine and dobutamine on oxygen transport and consumption in a dog model of endotoxic shock. AB - OBJECTIVES: Severe septic shock is associated with an imbalance between oxygen demand and oxygen supply (DO2) in the presence of an impaired oxygen extraction. Vasopressors are often used to restore a minimal perfusion pressure and inotropic agents are often used to increase myocardial contractility. However, optimal adrenergic support remains controversial. The present study investigated the effects of norepinephrine and dobutamine on DO2, oxygen consumption (VO2), and oxygen extraction in a dog model of endotoxic shock. DESIGN: Prospective, randomized, cross-over trial. SETTING: University intensive care laboratory. SUBJECTS: A total of 14 mongrel dogs anesthetized with pentobarbital and mechanically ventilated with air. INTERVENTIONS: The dogs received 2 mg/kg Escherichia coli endotoxin intravenously. After 30 mins, fluid administration with 0.9% saline was started to restore baseline filling pressures. The dogs randomly received dobutamine and norepinephrine. Each agent was infused for 20 mins followed by a drug free interval of 30 mins so that each dog could serve as his own control. Results for norepinephrine were grouped as low dose (0.1 and 0.2 micrograms/kg/min) and high dose (0.5 and 1.0 micrograms/kg/min). Results for dobutamine were also grouped as low dose (5 micrograms/kg/min) and high dose (10 micrograms/kg/min). MEASUREMENTS AND MAIN RESULTS: Norepinephrine increased both mean arterial pressure (MAP) and cardiac output without a significant change in systemic vascular resistance. Only high-dose norepinephrine increased DO2 (from 969 +/- 62 to 1240 +/- 49 mL/min [p < .001]) and VO2 (from 176 +/- 15 to 194 +/- 14 mL/min [p < .001]). Dobutamine increased both cardiac output and MAP. Both low and high-dose dobutamine increased DO2 (from 891 +/- 91 to 1142 +/- 99 mL/min [p < .001] and from 847 +/- 54 to 1317 +/- 75 mL/min [p < .001], respectively) and VO2 (from 172 +/- 14 to 182 +/- 15 mL/min [p < .001] and from 168 +/- 13 to 184 +/- 14 mL/min [p < .001], respectively). The increase in VO2 for a given increase in DO2 was higher with high-dose norepinephrine compared with high-dose dobutamine. When all doses were taken together, DO2 increased more with dobutamine than norepinephrine. Oxygen extraction decreased with all doses for both norepinephrine and dobutamine. CONCLUSIONS: In this endotoxic shock model, both norepinephrine and dobutamine can increase DO2 and VO2 but dobutamine caused a more consistent increase in these parameters. The decrease in oxygen extraction was relatively similar with dobutamine and norepinephrine. The present study does not support a significant beneficial effect of norepinephrine on the tissue extraction capabilities in endotoxic shock. PMID- 8440116 TI - Predictors of outcome in acute meningococcal infection in children. AB - OBJECTIVES: To develop a rapid and sensitive method for identification of patients at risk for organ system failure and death due to acute meningococcal infection, and to evaluate the reliability of the Pediatric Risk of Mortality score in predicting mortality rates from acute meningococcal infection. DESIGN: A prospective study which followed a retrospective analysis. SETTING: The Emergency Department and pediatric intensive care unit (ICU) of a university-affiliated children's hospital. PATIENTS: The hospital records of 86 pediatric patients with acute meningococcal infection during a 5-yr period (group 1) were reviewed. Twenty-two ICU patients (group 2) were then prospectively evaluated, and the occurrence rate of organ system failure was compared with that rate predicted by the model developed from the analysis of group 1. INTERVENTIONS: The occurrence of prognostic factors was compared with the development of organ system failure and death by Fisher's exact test and logistic regression analysis for patients in group 1. The mortality rates for groups 1 and 2 were compared with those rates that were predicted by the use of the Pediatric Risk of Mortality score. MAIN RESULTS: Eighteen of 86 patients in group 1 developed organ system failure, and seven (8.1%) patients died. Logistic regression analysis found that the combination of circulatory insufficiency, peripheral WBC counts of < 10,000 cells/mm3, and coagulopathy best predicted organ system failure. Ten of 22 patients in group 2 developed organ system failure, and two died. All patients with organ system failure exhibited > or = 1 of three identified prognostic factors. The probability of organ system failure occurring was > .5 for nine of ten patients with organ system failure. A total of nine patients in groups 1 and 2 developed multiple organ system failure, and all nine patients died. Based on Pediatric Risk of Mortality scoring, the mortality risk for nonsurvivors ranged from 27% to 94%, compared with 1% to 48% for survivors. The overall mortality rate was consistent with that rate predicted by the Pediatric Risk of Mortality scoring system. CONCLUSIONS: Patients with acute meningococcal infection who exhibit signs of circulatory insufficiency, a peripheral WBC count of < 10,000 cells/mm3, or a coagulopathy have a high probability of developing organ system failure. Death is highly probable when multiple organ system failure develops, and the overall mortality rate is accurately predicted by the Pediatric Risk of Mortality score. PMID- 8440117 TI - International standards for safety in the intensive care unit. The International Task Force on Safety in the Intensive Care Unit. PMID- 8440118 TI - Healthcare reform: the role of coordinated critical care. AB - OBJECTIVE: To evaluate and editorialize the evolving role of the discipline of critical care as a healthcare delivery system in the process of healthcare reform. DATA SOURCES: The sources included material from the Federal Office of Management and Budget, Health Care Financing Review, President Bush's Office, Association of American Medical Colleges, and publications of the Society of Critical Care Medicine. STUDY SELECTION: Data were selected that the author felt was relevant to the healthcare reform process and its implications for the discipline of critical care. DATA EXTRACTION: The data were extracted by the author to illustrate the forces behind healthcare reform, the implications for the practice of critical care, and role of critical care as a coordinated (managed) care system in the process of healthcare reform. DATA SYNTHESIS: Healthcare reform has been initiated because of a number of considerations that arise in evaluating the current healthcare delivery system: access, financing, cost, dissatisfactions with the mechanisms of delivery, and political issues. The reform process will occur with or without the involvement of critical care practitioners. Reforms may greatly alter the delivery of critical care services, education, training, and research in critical care. Critical care has evolved into a healthcare delivery system that provides services to patients who need and request them and provides these services in a coordinated (managed) care model. CONCLUSIONS: Critical care practitioners must become involved in the healthcare reform process, and critical care services that are effective must be preserved, as must the education, training, and research programs. Critical care as a healthcare delivery system utilizing a coordinated (managed) care model has the potential to provide services to all patients who need them and to deliver them in a manner that is cost effective and recognized as providing added value. PMID- 8440119 TI - Use of vitamin B12 in the treatment and prevention of nitroprusside-induced cyanide toxicity. AB - OBJECTIVE: To review the mechanism of action, safety, and efficacy of hydroxocobalamin in the treatment and prevention of nitroprusside-induced cyanide toxicity. DATA SOURCES: English and foreign-language journal articles and reference texts identified from Index Medicus. Both animal and human studies were included. DATA SYNTHESIS: High-dose or prolonged therapy with nitroprusside in patients with hepatic or renal dysfunction increases the risk for nitroprusside induced cyanide or thiocyanate toxicity, respectively. Hydroxocobalamin has been shown to significantly reduce RBC and plasma cyanide concentrations in animals and surgical patients without producing clinically important adverse effects or toxic metabolites. Thiosulfate infusions also decrease cyanide toxicity but can cause accumulation of thiocyanate resulting in clinical toxicity. Cyanocobalamin cannot effectively remove cyanide due to poor binding. CONCLUSIONS: Hydroxocobalamin is a safe and effective agent in the prevention and treatment of nitroprusside-induced cyanide toxicity. Prolonged or high-dose infusions of nitroprusside should be minimized in critically ill patients, especially if hepatic and/or renal dysfunction is present. PMID- 8440120 TI - Isoelectric electroencephalogram and loss of evoked potentials in a patient who survived cardiac arrest. PMID- 8440121 TI - Axillary vein cannulation in neonates. PMID- 8440122 TI - Guidelines for the use of innovative therapies in sepsis. PMID- 8440123 TI - Hazards of humidifiers with heated wires. PMID- 8440124 TI - Large-scale cryopreservation of isolated dog hepatocytes. AB - This study aimed to develop methods for the large-scale preparation of hepatocytes from large animal livers and for the mass cryopreservation of isolated hepatocytes. Isolated hepatocytes were obtained from Beagle dogs weighing around 10 kg by collagenase digestion plus preperfusion with the Ca2+ chelator ethylene glycol bis N,N'-tetraacetic acid. The cell yield was 2.1 +/- 0.45 x 10(10)/liver with 90% viability by the trypan blue dye exclusion test, and the estimated cell yield was 72 +/- 13%. The optimal conditions were large-scale cryopreservation of dog hepatocytes were (i) a freezing rate of 1-10 degrees C/min, (ii) a dimethyl sulfoxide (Me2SO) concentration of 20% (final concentration: 10%), (iii) a cell density that did not exceed 10(8)/ml, and (iv) rapid thawing in a 37 degrees C water bath. The viability of preserved hepatocytes was 75 +/- 3.0% and the estimated recovery rate was approximately 50%. Preserved hepatocytes showed 20-50% of the metabolic activity of fresh cells, as assessed by ammonia and fructose loading tests, ATP content, and [14C]leucine uptake. Following culture after thawing, the morphological normalization of preserved cells was confirmed by light and electron microscopy. PMID- 8440125 TI - Metabolic activity of freshly prepared and cryopreserved hepatocytes in monolayer culture. AB - The successful use of isolated hepatocytes for transplantation will, no doubt, require cryopreservation of the cells. However, cryopreservation results in the loss of viability of isolated hepatocytes. In this study a method is described that allows recovery of viable hepatocytes after cryopreservation. Freshly prepared and cryopreserved hepatocytes (1.8 M Me2SO in Euro-Collins solution) were suspended in Dulbecco's culture medium and allowed to form monolayers in Primaria T-25 culture flasks. Viable hepatocytes produced monolayers after 3 h of incubation and viable cultures could be maintained for up to 7 days as judged by trypan blue exclusion. Metabolic viability was measured by incorporation of radiolabeled isoleucine into proteins. Maximal protein synthetic capabilities in freshly prepared hepatocytes was obtained 24 h after culturing. Cryopreserved hepatocytes showed a decrease in protein synthetic capabilities after 24 h culturing. However, longer times of culture resulted in regenerating the capacity of these cryopreserved cells to carry out protein synthesis to levels similar to those of freshly prepared and cultured cells. Thus, incubation of monolayer cultures of cryopreserved hepatocytes for at least 48 h provides a means for reversing the injury caused by freeze-thaw stress and the regeneration of initial viability. This technique may provide a method that is suited for the use of cryopreserved hepatocytes for clinical transplantation. PMID- 8440126 TI - Cytotoxicity of amphotericin B for fibroblasts in human heart valve leaflets. AB - The cytotoxicity of amphotericin B (Fungizone, containing deoxycholate) was investigated for human heart valve leaflet fibroblasts. Leaflets were obtained from human aortic and pulmonic valves and incubated in culture medium containing amphotericin B. Upon completion of incubation, some leaflet sets were analyzed immediately, and others were cryopreserved and stored below -135 degrees C. Quantitative fibroblast viability assays were performed. The results can be summarized by consideration of the data obtained from autoradiographic analysis of [3H]proline incorporation into collagen. Incubation with 10 micrograms/ml amphotericin B at 37 degrees C resulted in approximately 11% loss of fibroblast viability. After cryopreservation, the leaflets incubated with amphotericin B experienced an additional 42% loss of fibroblast viability. These results indicate that use of amphotericin B, in this form, is ill advised for treatment of human heart valves prior to cryopreservation. PMID- 8440127 TI - Long-chain acyl-coenzyme A thioesters and renal hypothermic ischemic injury: effects of glycine flush. AB - The effects of hypothermic ischemia utilizing Euro-Collins flush on renal tissue long-chain activated fatty acid content was studied in dogs. Also, the ability of the simple amino acid glycine to complex these acyl thioesters was also investigated. Renal inner cortex was found to contain (in increasing amounts) myristoyl-, palmitoleoyl-, palmitoyl-, arachidonyl-, and oleoyl-coenzyme A throughout the 3 days of cold ischemia. Although the amounts of individual long chain acyl-CoA compounds varied considerably, the concentrations were not found to differ significantly with increasing ischemia times. The presence of 5 mM of glycine in the flush also did not influence the amount or species of long-chain acyl-CoA esters in renal tissue during cold ischemia. Ischemic renal tissue content of most long-chain acyl-CoA compounds was reduced by about 50% when the tissue underwent in vitro reperfusion with 37 degrees C O2-saturated media. Glycine included in the flush storage solution did not alter acyl-CoA levels in tissue undergoing hypothermic ischemia and short-term in vitro reperfusion with O2-saturated buffer. In conclusion, long-chain acyl-CoA thioesters are present during hypothermic renal ischemia and the levels of most of these species are reduced during in vitro reperfusion after ischemia. The quality and production mass of these metabolites appears to be unaltered by progressive hypothermic ischemia times. Finally, the protective effects of glycine in this model of renal organ preservation injury are not associated with reductions of renal tissue long chain activated fatty acids. PMID- 8440128 TI - Effects of various cryoprotective agents and membrane-stabilizing compounds on bull sperm membrane integrity after cooling and freezing. AB - In this study attempts were made to improve the survival rates of bull spermatozoa after freezing/thawing and to clarify the importance of certain agents to the cryopreservation of spermatozoa. For that purpose the standard freezing extender was modified by the addition of different concentrations of various cryoprotectants and membrane-stabilizing agents: glycerol, 1,2 propanediol, polyvinylpyrrolidone, sucrose, egg yolk, lipid vesicles, and bovine serum albumin (BSA). Sperm membrane impermeability toward H33258 was employed as the parameter for sperm integrity during cooling and after freezing/thawing. Exclusion of glycerol from the extender did not significantly affect sperm integrity. Replacing 6% glycerol by 6% 1,2-propanediol resulted in reduced sperm survival, whereas replacement of glycerol by 62.5 mM sucrose slightly improved survival rates. Addition of 5 or 10% polyvinylpyrrolidone (either or not in combination with 0.5 M sucrose) significantly reduced sperm integrity. Excluding egg yolk from the extender caused a serious decrease of sperm survival after both cooling and freezing. The cryoprotection offered by egg yolk could not be mimicked by dioleoylphosphatidylcholine (DOPC) vesicles or DOPC/phosphatidic acid/cholesterol vesicles in concentrations up to 29 or 9 mM, respectively. However, the freezing extender containing 6.5 mM DOPC vesicles in combination with 6% BSA yielded results which did not significantly differ from those obtained with the standard extender; higher vesicle concentrations combined with BSA might produce even better results. Further research on the cryopreservation of bovine spermatozoa should focus on membrane stabilization since the membrane stabilizing compounds yield more promising results than the ice-preventing agents. PMID- 8440129 TI - Contributions of cooling and warming rate and developmental stage to the survival of Drosophila embryos cooled to -205 degrees C. AB - Because of their high susceptibility to chilling injury, permeabilized Drosophila embryos can not be cryobiologically preserved by slow freezing at rates low enough to prevent the formation of intraembryonic ice. Calculations indicated that to outrun the chilling injury they must be cooled and warmed rapidly at an estimated 20,000 degrees C/min or faster. Ordinarily, such cooling rates would inevitably produce lethal intracellular ice. To prevent this, embryos must contain and be surrounded by sufficiently high concentrations of glass-promoting solutes to induce vitrification on cooling and prevent devitrification on warming. Like Steponkus et al. (Nature 345, 170, 1990) we have used ethylene glycol as the solute and have exposed permeabilized 12-h embryos to it in two steps. (Permeabilization was effected by exposing dechorionated embryos to a mixture of 0.3% 1-butanol in n-heptane for 90 or 110 s.) The two steps were (i) a 30-min exposure to 2 M ethylene glycol at 23 degrees C and (ii) a 5-min exposure to 8.5 M ethylene glycol [+/- 10% polyvinylpyrrolidone (PVP)] at 5 degrees C. The volumetric response to the first step indicates that full permeation of the 2 M glycol has been approached by 30 min. The point of the second step is to raise the intraembryonic concentration of ethylene glycol to near 8.5 M ethylene glycol by osmotic dehydration. Survival based on hatching is some 45% at this point. When 12-h embryos in 8.5 M glycol containing 10% PVP are then cooled to -205 degrees C at approximately 100,000 degrees C/min and warmed at about that rate, an average of about 12% survive (hatch), although in about half the runs 15-29% survive. Survivals in the absence of PVP are usually poorer but have been as high as 40%. Currently, 5% of the surviving larvae develop to adult flies (Steponkus et al. reported 18% hatching and 3% development to adult). Embryos that develop but do not hatch show readily detectable abnormalities in mouth parts and dorsal closure. Very high warming rates are much more critical to survival than are very high cooling rates; for example, none survive when warming is 2000 degrees C/min. The deleterious effect of slow warming is exerted between -80 and -40 degrees C. The lack of reciprocity between the effects of time spent cooling and time spent warming argues against ascribing death to chilling injury. Rather, it and other data argue for ascribing death to the devitrification during warming of cytoplasm that vitrified during cooling.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8440130 TI - Laboratory and animal model evaluation of the Cryotech LCS 2000 in hepatic cryotherapy. AB - Hepatic cryotherapy is increasingly used in the treatment of patients with multiple hepatic metastases, particularly from colorectal cancer. The Cryotech LCS 2000 system, with insulated shaft-circulated liquid nitrogen probes, was designed for this purpose and was evaluated on the bench and in an animal model. The 9-mm probe was considerably more effective than the 5-mm probe when judged on time to create an iceball of a given diameter. The use of thawing gas reduced the time until the probe could be removed from 25 to 5 min but heated gas only produced a further reduction of 2 min. In the animal model, significant reduction in treatment times occurred with vascular inflow occlusion. The zone of necrosis as a percentage of the original iceball diameter was significantly higher following a twin freeze/thaw cycle. The relationship of the edge of the iceball to the eventual zone of hepatic necrosis was studied using different unabsorbable markers. India ink and sutures proved unreliable but a Teflon cannula was more successful and the margin was only of the order of 2 mm. The discrepancy between this observation and the percentage of the original iceball diameter which apparently becomes necrotic (64 and 82%) for single- and double-freeze lesions, respectively, suggests that the cryolesion undergoes shrinkage within 1 month and that the diameter of necrosis underestimates the true zone of destruction. PMID- 8440131 TI - Effect of the composition of vitrification media on survival of rabbit embryos. AB - A total of 448 rabbit morula stage embryos were used to examine the effect of modified vitrification procedure and vitrification media containing 10% (1.36 M) glycerol, 20% (2.72 M) 1,2-propanediol, and 1 M sucrose. The best result, 89.5% embryos developed in vitro, was obtained after equilibration, vitrification, and dilution of embryos using media in which the salt concentration was maintained constant on a molar basis. Media prepared on a molal basis were more toxic and/or less efficient. PMID- 8440132 TI - Aortic dissection and aortic aneurysm surgery: clinical observations, experimental investigations, and statistical analyses. Part III. PMID- 8440133 TI - Regional sublocalization of the human thyroid peroxidase gene (TPO) by tritium and fluorescence in situ hybridization to chromosome 2p25-->p24. AB - Thyroid peroxidase (TPO), the enzyme responsible for thyroid hormone synthesis, is a key autoantigen in autoimmune thyroid disease. Based on the results of a study using both isotopic and nonisotopic in situ hybridization, we assign the gene coding for human TPO to chromosome region 2p25-->p24. PMID- 8440134 TI - Localization of the human alpha 2-plasmin inhibitor gene (PLI) to 17p13. AB - We previously assigned the human alpha 2-plasmin inhibitor gene (PLI) to 18p11.1- >q11.2 by isotopic in situ hybridization. However, results obtained subsequently via Southern blot analysis of somatic cell hybrids and fluorescence in situ hybridization studies indicate that the gene is located at 17p13. Accordingly, we reassign PLI to 17p13. PMID- 8440135 TI - Localization of the human vitamin D 24-hydroxylase gene (CYP24) to chromosome 20q13.2-->q13.3. PMID- 8440136 TI - Integration of the cytogenetic and genetic linkage maps of human chromosome 16 using 50 physical intervals and 50 polymorphic loci. AB - A comprehensive genetic linkage map constructed from 50 loci represented by 68 markers was anchored to 50 cytogenetically defined intervals on human chromosome 16. The linear order of the loci on the cytogenetic map was compatible with the independently derived linear order on the genetic map. The sex-averaged genetic length is 164.5 cM, with an average distance between loci of 3.3 cM. Sex-specific distances are 132.8 cM in males and 201.8 cM in females. This is the first detailed synthesis of genetic and cytogenetic maps for any human chromosome and is the first step in correlating the genetic and physical maps of this chromosome. The combined map, containing 15 loci with a minimum heterozygosity of 60% and 6 PCR-formatted microsatellite markers, will be useful for assignment and regional localization of disease genes to this chromosome. PMID- 8440137 TI - Analysis of sperm chromosome complements from a man heterozygous for a pericentric inversion, inv(8)(p23q22). AB - Human sperm chromosomes were studied in a man heterozygous for a pericentric inversion (p23q22) of chromosome 8. The pronuclear chromosomes were analyzed after in vitro penetration of golden hamster eggs. A total of 166 sperm were examined; 88.6% were chromosomally balanced and 11.4% were recombinant. Of the balanced complements, the proportion with a normal chromosome 8 (53.6%) was approximately equal to the proportion with an inverted 8 (46.4%). Of the recombinant complements, the proportion of sperm with a duplication of 8q and a deletion of 8p (5.7%) was equal to the reciprocal event of a duplication of 8p and a deletion of 8q (5.7%). The frequencies of X-bearing (53.2%) and Y-bearing sperm (46.8%) were not significantly different from the expected 1:1 ratio. There was no evidence for an interchromosomal effect. A total of four pericentric inversions have been studied by human sperm chromosome analysis; recombinant chromosomes have been observed in two of the four cases. PMID- 8440138 TI - In humans all U3 genes map to chromosome 17p12-->p11, but in mouse the U3A and U3B genes are located on different chromosomes. AB - U3 small nucleolar RNA, which participates in eukaryotic rRNA processing, is encoded by a small multigene family in mammals. In humans, the four to six gene copies code for an identical U3 RNA molecule; rodents, however, have two variant forms of these genes, U3A and U3B. We show that all U3 genes in humans map to a single chromosomal locus, 17p12-->-p11, which corresponds exactly to the region of mouse Chromosome 11 where the four U3B genes are clustered. By contrast, in mouse the unique U3A gene copy is not linked to the U3B gene cluster but maps to another chromosome (the B2-B4 region of Chromosome 10). PMID- 8440139 TI - Newly acquired peri-telomeric heterochromatin in a transgenic mouse lineage. AB - Karyotypes of an embryonic stem cell line and normal bone marrow and peripheral blood cells from a transgenic mouse lineage, strain 83, exhibit a novel region of constitutive heterochromatin in the peri-telomeric region of chromosome 3. This heterochromatic region co-localizes with the integration site of the transgene, an 11-Mb tandem insertion of a plasmid containing human beta-globin gene sequences, and is inherited in Mendelian fashion. The significance of this finding is discussed, and a nomenclature for such newly acquired heterochromatic regions is suggested. PMID- 8440140 TI - Chromosomal localization of omega and trophoblast interferon genes in cattle and river buffalo by sequential R-banding and fluorescent in situ hybridization. AB - Fluorescent in situ hybridization (FISH) of the cattle cDNA probe bTP-509 to RBA banded cattle (Bos taurus L.) chromosomes confirmed the assignment of the omega (IFNW) and trophoblast (IFNT) interferon genes to chromosome 8q15. Using the same probe, these genes were also localized to river buffalo (Bubalus bubalis L.) chromosome 3q15 following sequential RBA-banding and FISH. The extensive G- and R banding homology observed between cattle chromosome 8 and river buffalo chromosome arm 3q supports the conserved chromosomal location of the IFNW and IFNT genes in these two species. PMID- 8440141 TI - A simple G-banding technique following nonradioactive in situ hybridization. AB - A simple G-banding protocol has been found to be compatible with a nonisotopic in situ hybridization technique utilizing a biotin-streptavidin-polyalkaline phosphatase complex. The chromosomes are banded following detection of the hybridization signal, the procedure requires no pretreatment of cultures or special optical equipment, and it produces permanent preparations. PMID- 8440142 TI - Detection of a new submicroscopic Norrie disease deletion interval with a novel DNA probe isolated by differential Alu PCR fingerprint cloning. AB - Differential Alu PCR fingerprint cloning was used to isolate a DNA probe from the Xp11.4-->p11.21 region of the human X chromosome. This novel sequence, cpXr318 (DXS742), detects a new submicroscopic deletion interval at the Norrie disease locus (NDP). Combining our data with the consensus genetic map of the proximal short arm of the X chromosome, we propose the physical order Xcen-DXS14-DXS255 (DXS426, TIMP)-(DXS742-([MAOB-MAOA-DXS7], NDP)-DXS77-DXS228)-DXS209-DXS148-DXS196 ++ +Xpter. The cpXr318 probe and a subclone from a cosmid corresponding to the DXS7 locus were converted into sequence-tagged sites. Finally, DXS742, DSX7, DXS77, and MAOA were integrated into a physical map spanning the Norrie disease locus. PMID- 8440143 TI - Linkage analysis of the monoamine A and B genes using newly-defined polymorphisms. AB - The monoamine oxidase A (MAOA) and B (MAOB) genes have been localized to chromosome Xp11.3. Recently-defined polymorphisms and linkage analysis have shown tight linkage between MAOA and MAOB, with a distance of approximately 2.7 cM between them. PMID- 8440144 TI - Chromosome banding in Amphibia. XIX. Primitive ZW/ZZ sex chromosomes in Buergeria buergeri (Anura, Rhacophoridae). AB - The karyotype of the common bell-ring frog, Buergeria buergeri, is characterized by primitive ZW/ZZ (female/male) sex chromosomes. The only difference between the Z and W is the presence of a nucleolus organizer region (NOR) and its associated constitutive heterochromatin in the Z. This causes a sex-specific difference in the number of ribosomal RNA genes, with a male:female ratio of about 2:1. In the cell nuclei of the various tissues analyzed the NORs on both Z chromosomes are transcriptionally active. During meiosis in females, the ZW chromosomes form a characteristic lampbrush sex bivalent with a conspicuous absence of chiasmata along half of their long arms. No further morphological differences are present in these primitive sex chromosomes. The results indicate that there is no Z chromosome inactivation mechanism operating in this amphibian. Experimental sex reversal of genetic (ZW) females to functional males was achieved by estrogen treatment of tadpoles. Mating of sex-reversed females with normal females yields the expected 25% lethal nucleoli-less WW embryos, which die at the tail-bud stage. The sex of the remaining viable embryos with one or two nucleoli determined after metamorphosis was in a female:male ratio of 1.57:1. These genetic experiments confirm that a primitive ZW/ZZ (female/male) type of chromosomal sex determination operates in this species. PMID- 8440145 TI - Micromanipulation by "multiple" optical traps created by a single fast scanning trap integrated with the bilateral confocal scanning laser microscope. AB - We have developed a novel micromanipulator consisting of multiple optical traps created by scanning one single beam trap along a variable number of positions. Among other things, this enables the orientation of irregularly shaped and relatively large structures which could not be oriented by just one trap as is demonstrated on long Escherichia coli bacteria filaments. We expect that the multiple trap manipulator will broaden the field of applications of optical trapping as a micromanipulation technique. For example, it facilitates the study of mechanical properties of extended structures as illustrated by a "bending" experiment using E. coli bacterium filaments. A special application of the multiple trap manipulator is the "indirect trapping" of objects which we did by keeping them held between other optically trapped particles. Indirect trapping makes it possible to trap particles which either cannot be trapped directly due to their optical properties (refractive index) or for which exposure to the laser radiation is undesirable. The multiple optical trap manipulator is controlled interactively by a UNIX workstation coupled to a VME instrumentation bus. This provides great flexibility in the control of the position and the orientation of the optical traps. Micromanipulation makes it desirable to have real time 3D microscopy for imaging and guidance of the optical traps. Therefore we integrated optical micromanipulation and a specially developed real-time confocal microscope. This so called bilateral confocal scanning laser microscope (bilateral CSLM) [Brakenhoff and Visscher, J Microsc 165:139-146, 1992] produces images at video rate. PMID- 8440146 TI - Pulse modulation of the excitation light source boosts the sensitivity of an arc lamp-based flow cytometer. AB - It has been found that the type of short arc high-pressure lamps used in some flow cytometers can be pulsed to reach intensities many times higher than that measured when they are operated on constant power. A 75 W mercury-xenon lamp was fed 20 microseconds current pulses super-imposed on its rated current of 5.4 A. Pulses of 50 A produced a 75-fold increase of the emission intensity at the excitation wavelength of FITC, which means that the excitation intensity in the flow chamber at this wavelength exceeded 100 mW. At the major emission lines of mercury, i.e., 366, 436, and 546 nm, the increase was about 25-fold, corresponding to intensities of the order of 300 mW. The light pulses were found to be reproducible to within 2% and the intensity was independent of the pulse frequency up to at least 250 pulses/s. Operated in this mode the lamp produced more than 1 x 10(8) 30 A pulses, which is sufficient to measure some 10,000 typical size samples. The rise time of the light pulses was about 5 microseconds. This was sufficiently short that the leading edge of the light scattering signal from a cell entering the excitation focus of the flow cytometer could be used to trigger the current pulse so that the cells were exposed to the full light pulse intensity while they were still within the focus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8440147 TI - Phase-resolved fluorescence lifetime measurements for flow cytometry. AB - A flow cytometer capable of measuring fluorescence lifetimes by the phase shift method has been built and evaluated. Under optimal conditions, the resolution of the fluorescence lifetime measurement is shown to be under 200 picoseconds. Pulse intensity variations are normalized using limiting amplifiers and electronic filtering. Normalization of signal intensities provides a lifetime measurement that is independent of fluorescence intensity over at least a 50-fold (17 dB) range in fluorescence intensity. The fluorescence lifetimes of unbound dye, fluorescent beads, cells stained with ethidium bromide, propidium iodide, and phycoerythrin-conjugated monoclonal antibodies have been measured. The fluorescence lifetimes measured for these particles are well correlated with lifetime measurements made using a standard fluorimeter. Cells stained with ethidium bromide and propidium iodide at various nucleotide-to-dye ratios are shown to exhibit similar behavior to static cuvette measurements. The fluorescence lifetime parameter is also shown to resolve phycoerthyrin fluorescence from propidium iodide fluorescence. PMID- 8440148 TI - Immunofluorescent evaluation of DNA repair synthesis using interactive laser cytometry. AB - An improved differential fluorescence analysis technique which employs scanning laser cytometry for the detection of two DNA binding fluorochromes was used to quantitate both total DNA and cellular incorporation of the base analogue, bromodeoxyuridine (BrdUrd), into UV- or methyl methane sulphonate (MMS)-treated DNA. In this procedure DNA containing BrdUrd was partially denatured and immunolabeled by binding anti-BrdUrd monoclonal IgG to incorporated BrdUrd. Anti BrdUrd was detected with a secondary fluorochrome-labeled polyclonal anti-IgG. Cells were counterstained with propidium iodide to allow the determination of total DNA. Fluorescence was determined using the Meridian ACAS 570 Scanning Laser Cytometer. The computer-analyzed images were generated from monodisperse populations of UV- or MMS-treated cells, allowing the evaluation of DNA synthesis associated with excision repair and of total DNA content in single cells. These data were compared with 3H-thymidine incorporation occurring as a function of excision repair. The analysis of DNA synthesis with this technique is consistent, relatively simple, and rapid with excellent sensitivity and provides a viable method for determining cycling vs. non-cycling cells, total cellular DNA, and excision repair-associated DNA synthesis of individual cells within heterogeneous cell populations. PMID- 8440149 TI - Statistical confirmation that immunofluorescent detection of DNA repair in human fibroblasts by measurement of bromodeoxyuridine incorporation is stoichiometric and sensitive. AB - Diploid human fibroblasts (IMR-90 cells), grown to confluency and growth-arrested by serum starvation, were irradiated with a variety of doses of UV light (0.025 40 J/m2) or incubated with broad dose ranges of four direct-acting mutagens [ethyl methanesulfonate (EMS), ICR-170, methyl methanesulfonate (MMS), and 4 nitroquinoline oxide (4-NQO)] and pulsed with a thymidine analog, 5 bromodeoxyuridine (BrdUrd) to detect evidence of DNA repair. These cells and appropriate controls were immunochemically stained and subjected to flow cytometric analysis to quantify BrdUrd incorporation into DNA and simultaneously measure cellular DNA content. Since the maximal quantity of BrdUrd incorporated with repairing cells is profoundly less than the amount incorporated during replicative synthesis and flow cytometric analysis collects information on a cell to-cell basis, data collection using linear histograms succeeded both in revealing repairing cellular populations and eliminating replicative cells from the analysis. Technical modifications necessary to achieve stoichiometry with UV irradiated IMR-90 fibroblasts included a 48h repair (and pulse) period, followed by denaturing cellular DNA for 15 min at 90 degrees C. The limit of detection was equal to or below the lowest dose investigated (0.025 J/m2). DNA repair was also detected with cultures incubated with low doses of all chemicals and pulsed with BrdUrd for a 24 h period. The limits of detection were near or below 500 microM EMS, 5 microM MMS, 0.25 microM 4-NQO, and 0.1 microM ICR-170. PMID- 8440151 TI - Shape changes in Escherichia coli B/r A during agar filtration. AB - We have investigated the phenomenon of shape distortion in a sample of 1,552 Escherichia coli B/r A cells in balanced exponential growth, during preparation for electron microscopy by agar filtration. Mixed preparations of bacterial cells and polystyrene latex spheres were shadow cast at low angle and the resulting shadows used to obtain quantitative estimates for the dimensions of the dehydrated cells; these then serve as a basis for a model of its shape in three dimensions. A statistical analysis of the projections of clustered cells and the intervening fissures, in nonshadow-cast preparations, provides an estimate of the effects of drying. The average width of the dehydrated cell (450 nm) is about 20 nm greater than the diameter of the live bacterium, whereas its length (1,398 nm) is approximately 40 nm less. PMID- 8440150 TI - Flow cytometric analysis of two incorporated halogenated thymidine analogues and DNA in a mouse mammary tumor grown in vivo. AB - A technique was developed for the staining of nuclei for DNA using propidium iodide, and incorporated chlorodeoxyuridine (CldUrd) and iododeoxyuridine (IdUrd) using two monoclonal antibodies that showed negligible cross-reactivity. The mouse mammary solid tumor MCaK was labeled in vivo by intraperitoneal injection of the nucleosides. Tumor cell nuclei were stained after isolation from ethanol fixed solid tumor tissue and acid denaturation. The Br3 antibody, which specifically recognizes CldUrd, was applied first, followed by indirect staining with goat anti-mouse phycoerythrin. The direct fluorescein isothiocyanate conjugate of the B44 antibody, which specifically recognizes IdUrd, was then applied. In the direct conjugate form this antibody reacted only minimally with CldUrd. The nuclei were then stained with propidium iodide. With this dye combination the coefficients of variations of the DNA histograms were consistently in the 2-4% range. Two other dye combinations were compared. The propidium iodide/phycoerythrin/fluorescein isothiocyanate dye combination was the simplest because of the compatibility with single laser flow cytometry. PMID- 8440152 TI - Flow cytometric clonal excess analysis of peripheral blood, routine handling, and pitfalls in interpretation. AB - Clonal excess (CE) analysis by flow cytometry is a convenient method to detect minimal involvement of peripheral blood and bone marrow by B-cell lymphoma. The method is based on evaluation of the congruity between kappa and lambda light chain distributions within a normal B-cell population. By using the Kolmogorov Smirnov method for evaluation of histogram identity, the maximum difference (D value) between distributions is calculated. However, variable adsorption of cytophilic plasma immunoglobulin (Ig) to CD16 positive cells, T-cell subsets, and the B cells themselves may cause incongruity between the light chain distributions that might simulate or disguise a true clonal excess and thus create major pitfalls in the interpretation of the CE analysis. These phenomena are observed both in normal blood donors and in patients with non-Hodgkin's lymphoma. In the present report we describe: (1) how freezing of the isolated mononuclear cells before immunostaining effectively removes most of the adsorbed cytophilic Ig, (2) how by exclusion of the CD16 positive population further resolution of the relevant histogram shape is obtained to avoid false interpretations of incongruity, and (3) how adsorption of Ig to B-cells creates a typical pattern of "reciprocal labeling" that can be mistaken for a clonal excess. Based on our observations we argue against an uncritical use of normal D values for definition of clonal excess and advocate an analytic evaluation of the kappa and lambda overlay distribution by dual immunofluorescence, either by excluding CD16 positive cells or by including only B cells, to reveal the nature of the different deviations. PMID- 8440153 TI - Flow cytometric analysis of DNA and nuclear protein in paraffin-embedded tissue. AB - Previously we described the simultaneous quantification of DNA and nuclear protein in unfixed tissue from solid tumors. The resultant 2 parameter flow cytometric analysis has several advantages over that of DNA alone. In this report, we describe a modification of the technique for the analysis of formalin fixed paraffin-embedded tissue. Paraffin-embedded material was prepared by hydrating sections, incubating in 0.5% pepsin solution, washing, and resuspending in buffer containing nonionic detergent. The nuclei were then stained with fluorescein isothiocyanate and propidium iodide in the presence of ribonuclease. Several solid tumor tissue types have been analyzed, including breast, colon, kidney, and thymus. The best results were obtained when the initial pepsin treatment was for 1.5 h, instead of 0.5 h. Pepsin treatment for 1.5 h improved the CVs of both the DNA and nuclear protein parameters, and did not appear to reduce nuclear protein levels or to cause significant disintegration of nuclei. The DNA/nuclear protein histograms of unfixed and fixed, paraffin-embedded tissue were similar. Since tumor nuclei typically have higher protein levels than DNA diploid nuclei, the technique reduces population overlapping and permits less subjective identification of DNA aneuploidy. PMID- 8440154 TI - Resolution of fluorescence signals from cells labeled with fluorochromes having different lifetimes by phase-sensitive flow cytometry. AB - A flow cytometric method has been developed that uses phase-sensitive detection to separate signals from simultaneous fluorescence emissions in cells labeled with fluorochromes having different fluorescence decay lifetimes. By CHO cells were stained with propidium iodide (PI) and fluorescein isothiocyanate (FITC). These dyes bind to DNA and protein and the fluorescence lifetimes of the bound dyes are 15.0 and 3.6 ns, respectively. Cells were analyzed as they passed through a modulated (sinusoidal) laser excitation beam. Fluorescence was measured using only a long-pass filter to block scattered laser excitation light and a single photomultiplier tube detector. The fluorescence detector output signals were processed by dual-channel phase-sensitive detection electronics and the phase-resolved PI and FITC signals were displayed as frequency distribution histograms and bivariate plots. By shifting the phase of one detector channel reference signal by pi/2 + phi 1 degrees and the phase of the other detector channel reference signal by - pi/2 + phi 2 degrees, where phi 1 and phi 2 are the phase shifts associated with the PI and FITC lifetimes, the PI and FITC signals were separately resolved at their respective phase-sensitive detector outputs. This technology is also applicable to suppressing background interferences caused by cellular autofluorescence, unbound/free dye, nonspecific dye binding, and Raman and Rayleigh scattering. PMID- 8440155 TI - Use of mouse hepatocytes for the flow cytometric determination of DNA levels of nuclei extracted from fresh tissue of hybrid larch (Larix x eurolepis Henry). AB - A rapid and reliable method is presented to release intact nuclei from small amounts (100 mg) of fresh plant tissue. Further, an accurate and readily accessible new standard is proposed. Both techniques have potential application for many plant systems. The system chosen as a standard (inbred mouse strain Balb/C or B6/AF1 hepatocyte nuclei) contains both diploid and polyploid cells. This system was applied in the flow cytometric determination of absolute nuclear DNA values of female gametophytes and in vitro propagated shoots of hybrid larch (Larix x eurolepis Henry). The amount of DNA in 2C nuclei of in vitro grown larch is 32.48 +/- 4.04 or 31.97 +/- 6.14 pg/nucleus, respectively, when calculated using the mouse hepatocyte 4C or 8C nuclear peak as a reference standard. The amount of DNA in female gametophyte nuclei is 17.47 +/- 1.33 pg DNA/nucleus when these haploid larch nuclei were analyzed with trout red blood cell nuclei as the standard. When hepatocyte 4C nuclei were used as a standard, the absolute value of DNA per haploid larch nucleus was estimated as 16.8 +/- 0.53 pg. Plant tissue with as little as 4-6 pg DNA/nucleus up to as much as 35 pg DNA/nucleus can be tested using mouse hepatocytes as a standard while retaining an optimal sample/standard ratio. PMID- 8440156 TI - Changes in intracellular free calcium during hyperthermia: effects of local anesthetics and induction of thermotolerance. AB - We wished to determine if local anesthetics (LAs) induced changes in intracellular free calcium ([fCa2+i]) that could have an effect on cell killing by hyperthermia. Flow cytometry was used to measure [fCa2+i] of mouse NIH 3T3 cells during heating at 45.5 degrees C. In both non-tolerant and thermotolerant cells, heating caused a rapid increase (within 1 min) in [fCa2+i] of approximately 100 nM, which remained relatively constant during 25 min of continued heating; however, survival was higher in thermotolerant cells. Procaine, lidocaine, and tetracaine had no effect on survival or [fCa2+i] of cells kept at 37 degrees C up to 25 min. Cells heated with procaine and lidocaine showed no difference in [fCa2+i] compared to cells heated without LAs but were greatly sensitized to killing. Cells heated with tetracaine became permeable to trypan blue within 10-15 min of heating. We conclude that heat sensitization by LAs does not involve changes in [fCa2+i]. Furthermore, these studies reject the hypothesis that changes in [fCa2+i] are involved in heat-induced cell killing. PMID- 8440157 TI - Flow injection cytometry: a new approach for sample and solution handling in flow cytometry. AB - A prototype instrument for sample and solution handling in flow cytometry has been constructed. The system is modular and allows the control of any combination of up to 4 pumps, 2 selection valves, and 2 injection valves. These devices are controlled by a computer using TTL-logic. The flow injection instrument is interfaced to the flow cytometer via a 6-port injection valve, thereby facilitating virtually any flow pattern to be implemented without affecting the fluidics of the cytometer. Salient features of the instrument are accurate control of the volume of injected sample and reagent, reproducible timing, and controlled mixing conditions. Results from model experiments of on-line staining of trout erythrocytes with different concentrations of 4',6-diamidino-2 phenylindole (DAPI) and propidium iodide (PI) are shown. Possible ways to improve the performance and utility of the instrument are also discussed. PMID- 8440158 TI - Haemophilus influenzae B immunisation. PMID- 8440159 TI - Caution with disposable soft contact lenses. PMID- 8440160 TI - [The effect of captopril in nitrate tolerance]. AB - To test whether angiotensin-converting-enzyme (ACE) inhibitor can counteract nitrate tolerance, 15 men (mean age 65 [55-69] years) were studied. They all had an at least 75% stenosis of a main coronary artery branch, proven by coronary angiography no longer than 6 months previously. Each patient underwent six ergometric tests (two each per day on alternate days) at constant exercise level and duration: the sum of S-T segment depressions was measured during the recovery and exercise minutes. The initial ergometry test was done without medication, when the S-T segment sum was 1.15 +/- 0.20 mV. After 25 mg captopril (2nd ergometry period) this sum fell to 0.80 +/- 0.18 mV. Two hours after application of a nitrate plaster the S-T segment sum was 0.55 +/- 0.12 mV (3rd ergometry period). Adding 25 mg captopril a further reduction to 0.35 +/- 0.10 was achieved (4th ergometry period). Subsequently, continuous nitrate application brought about nitrate tolerance. The 5th ergometry period then produced a sum of S-T segment depressions of 0.85 +/- 0.18 mV. Renewed captopril administration reduced this value to 0.50 +/- 0.13 mV (57% of the initial value). The effect of captopril in nitrate tolerance is apparently due to an addition of the anti ischaemic action of the ACE inhibitor (31%) and the residual effect of the nitrate (26%). PMID- 8440161 TI - [The tryptophan-associated eosinophilia-myalgia syndrome. A clinical follow-up of 8 patients]. AB - Seven women and one man aged from 51 to 70 years suffered from eosinophilia myalgia syndrome after taking medicines containing tryptophan for depression or sleep disorders; the total duration of intake ranged from three to 106 months and the average daily dose was 1312 mg. All the patients had muscle pains and skin lesions resembling scleroderma together with impairment of general well being; six of them had high eosinophil counts of up to 2,600 cells/microliters (mean 1,629); other symptoms were weight loss, pruritus, fever, dyspnoea and sensory abnormalities. Discontinuation of tryptophan combined with systemic treatment with prednisone in doses of 32 or 20 mg/d for 4 to 16 weeks soon brought the eosinophil counts down, but the skin lesions, muscle pains and other symptoms showed little improvement over a follow-up period averaging 17.1 months. Treatment with penicillin G (20 mega-units daily for 14 days), azathioprine (100 mg daily for 2 months) or cyclosporin (2.5 mg/kg.day) was tried in some cases but had no significant effect. PMID- 8440162 TI - [Chronic bismuth poisoning with encephalopathy and dementia]. AB - A 58-year-old woman developed severe progressive dementia. Markedly impaired memory, apraxia and abnormal behaviour with psychotic components suggested Alzheimer's syndrome. But there were atypical signs, namely abnormal coordination, occasional tremors and dysarthria. A search for a possible toxic cause was at first unsuccessful, but by chance a "gastric power" containing 0.1 g of bismuth gallate per gram of powder, was found in her night-table. The patient had taken it regularly over years, at a dosage of up to 1.5 g daily, to combat gastric acidity. Six days after stopping the drug the blood bismuth level was 70 micrograms/l, which within 1-2 months fell to 9 micrograms/l. After 4 1/2 months in hospital the patient was discharged in a good general condition and with normal intellectual function. PMID- 8440163 TI - [The diagnosis of primary hemochromatosis]. PMID- 8440164 TI - [Omeprazole. Its pharmacology and therapeutic efficacy]. PMID- 8440165 TI - [Endoscopic sonography in extrahepatic obstructive jaundice]. PMID- 8440166 TI - [Baker's asthma]. PMID- 8440167 TI - [The state of knowledge and the duration of medical activity]. PMID- 8440168 TI - In vivo regulation of recombinant cardiac myosin heavy chain gene expression by thyroid hormone. AB - Cardiac myocytes have the unique ability to express exogenous genes that have been injected directly into the heart tissue in vivo. This technique makes it possible to identify cis-acting DNA sequences responsible for the regulation of myocyte-specific genes in a working heart. In these studies we introduced recombinant plasmids containing 5'-flanking sequences of the alpha-myosin heavy chain (alpha MHC) gene into the rat myocardium in order to identify sufficient promoter/enhancer sequences that faithfully reproduced the activity of the endogenous gene. The transcriptional activity of the alpha MHC promoter sequence was measured by the level of activity of the firefly luciferase reporter gene and was reported as the activity relative to a coinjected constitutively active viral promoter construct (pRSVCAT) which corrected for variations in DNA uptake and posttranscriptional events. We report that a recombinant plasmid containing 5' flanking sequences -2560 to +421 basepairs of the transcriptional start site of the alpha MHC gene was appropriately inactive in the hypothyroid rat heart, in which expression of the endogenous gene was also inhibited. The activity of this promoter sequence was increased 44-fold by thyroid hormone in the hearts of thyroidectomized rats. In contrast, although this recombinant plasmid was appropriately active in the euthyroid myocardium, its activity could not be further stimulated by thyroid hormone. The observation that regulation of the transcriptional activity of the alpha MHC promoter by thyroid hormone was different in euthyroid and hypothyroid hearts suggests that the participation of nuclear regulatory factors, including the thyroid hormone/retinoid family of receptors, may differ according to thyroid status. PMID- 8440169 TI - Biochemical properties of the agonist-induced desensitization of the follicle stimulating hormone and luteinizing hormone/chorionic gonadotropin-responsive adenylyl cyclase in cells expressing the recombinant gonadotropin receptors. AB - In most experiments done in cell-free systems, the LH/CG-induced desensitization of the ovarian LH/CG-responsive adenylyl cyclase has been reported to be dependent on GTP. Little is known, however, about the molecular basis of this phenomenon or about the FSH-induced desensitization of the FSH-responsive adenylyl cyclase. We report here that, contrary to most previous findings, ATP is required for desensitization of the LH/CG- and FSH-responsive adenylyl cyclase in human kidney cells stably transfected with the complementary DNAs for the rat LH/CG or FSH receptor. This requirement does not seem to be peculiar to transfected cells because under our experimental conditions ATP is also preferred over GTP for the human CG-induced desensitization of the LH/CG-responsive adenylyl cyclase in highly purified plasma membranes from MA-10 Leydig tumor cells. Maximal desensitization of both FSH- and LH/CG-sensitive adenylyl cyclase in membranes from the transfected cells was achieved with millimollar concentrations of Mg2+ and ATP and did not appear to correlate with activation of the enzyme. In both of these systems, GTP, uridine triphosphate, and cytidine triphosphate were not able to substitute for ATP. In MA-10 membranes, however, there was some desensitization even without added nucleotide triphosphates, and ATP was more potent than GTP. Last, desensitization of the gonadotropin-sensitive adenylyl cyclase could not be explained by a decrease in the functional activities of stimulatory guanine nucleotide binding protein or of the catalytic moiety of the enzyme. A change in the functional properties of the gonadotropin receptors appears to be the most likely mechanism for desensitization. PMID- 8440170 TI - Identification of binding proteins for nuclear localization signals of the glucocorticoid and thyroid hormone receptors. AB - Nuclear entry of proteins the size of the glucocorticoid and thyroid hormone receptors appears to be mediated by an interaction of nuclear localization signals (NLSs) within the proteins and specific NLS-binding proteins. NLSs have been identified in the hinge region of both receptors. We have identified the cellular binding proteins of the glucocorticoid receptor NLS and the thyroid hormone receptor NLS after cross-linking of radiolabeled signal peptides to subcellular fractions. Two S49 lymphoma cytosolic polypeptides of 60 and 76 kilodaltons (kDa) were specifically bound to either the glucocorticoid or thyroid hormone receptor NLS. The two binding sites demonstrated saturable binding. A competitive binding assay showed that the binding sites were specific for NLSs and that a mutated NLS was a poor competitor for the binding of labeled glucocorticoid receptor NLS. However, competition studies with peptides unrelated to NLSs, yet resembling NLSs in that they had a net positive charge, revealed that the 60-kDa entity demonstrated greater specificity for binding to NLSs than did the 76-kDa polypeptide. Glucocorticoid receptor NLS and thyroid hormone receptor NLS-binding proteins of 60 and 76 kDa were also identified in nuclear fractions. Although the unoccupied glucocorticoid receptor resides in the cytoplasm, while the unoccupied thyroid hormone receptor is always found in the nucleus, the hinge NLS interactions do not specify these different localizations of the unoccupied receptors. Rather, the data support roles for the hinge NLS in general steps of nuclear import and the 60-kDa cross-linked product as a chaperone of both receptors into the nucleus. Its cellular localization also suggests a role for the 76-kDa cross-linked product as a chaperone, but its relatively less stringent binding specificity may indicate that this polypeptide has a different physiological function. PMID- 8440171 TI - Diurnal pattern of pulsatile luteinizing hormone and testosterone secretion in adult male rhesus monkeys (Macaca mulatta): influence of the timing of daily meal intake. AB - Adult male rhesus monkeys have a diurnal pattern of reproductive hormone secretion that is characterized by significantly elevated LH and testosterone secretion in the evening hours and a nadir in secretion of these hormones in the morning. To test the hypothesis that the daily pattern of food intake may play a role in regulating the diurnal pattern of reproductive hormone secretion we performed three studies. First, to determine the relationship between the timing of the diurnal rise in LH secretion and meal consumption, blood samples were collected from 13 adult male rhesus monkeys via chronically indwelling venous catheters (samples every 15-20 min from 0800-0800 h) while monkeys were maintained on the standard feeding regimen in our colony (one meal of Purina monkey chow fed between 1100 and 1200 h). On a day of normal feeding there was a significant diurnal rhythm in mean LH concentrations with elevated levels at night (nadir: 13.41 +/- 0.82 ng/ml from 0800-1100 h; peak: 21.34 +/- 1.56 ng/ml from 2000-2300 h, P < or = 0.05). The rising phase of the diurnal rhythm in LH secretion was apparent starting in the early afternoon, shortly after the daily meal, at 1400 h (5 h before lights went off at 1900 h), and the diurnal rise in LH secretion was no longer apparent by 0500 h (several hours before the lights went on at 0700 h). Second, we examined the influence of missing the daily meal on the diurnal pattern of LH and testosterone secretion. Blood samples were collected for a 24-h period on a day of fasting from 9 monkeys. On a day of fasting there was no diurnal rise in plasma LH or testosterone concentrations; plasma concentrations of these hormones remained at the low morning levels throughout the day. Third, we examined the diurnal pattern of LH and testosterone secretion after adapting 5 monkeys (for 6-8 weeks) to a new meal time that was 6 h later in the day than the standard meal time (i.e. at 1700 h). After adaptation to this later feeding time monkeys showed a 6-h delay in the time of the first significant rise in LH secretion (which occurred at 2000 h).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8440172 TI - Tissue distribution and ontogeny of growth hormone receptor messenger ribonucleic acid and ligand binding to hepatic tissue in the midgestation sheep fetus. AB - While circulating GH concentrations are high in fetal life, skeletal growth is only slightly reduced by GH deficiency in utero. This has been explained by the relatively low binding of GH to fetal hepatic tissue, suggesting a lack of GH receptors (GHR). The GHR also recognizes ovine placental lactogen (oPL), which may have a specific role either as a fetal growth-promoting hormone or in regulating fetal metabolism. We investigated GHR expression and membrane binding of ovine (o) GH and oPL in various ovine fetal tissues and in maternal liver at different gestational stages. Singleton-bearing ewes at 51, 95, and 120 days gestation were killed. Liver, muscle, kidney, and brain samples were taken from the fetuses as well as placentas and livers from the ewes (n = 3/gestational age). GHR mRNA measured by Northern blot analysis was expressed at high levels in maternal liver at all gestational stages. A major band was observed at 4.4 kilobases (kb), and three minor bands were observed at 2.5, 1.7, and 8.1 kb. In fetal and placental tissue, only the 4.4-kb band was detected. This was present as early as day 51 of gestation in liver, kidney, lung, heart, and placenta and increased slightly with advancing gestation. On day 51, the expression of GHR mRNA in muscle was negligible, but by day 95, muscle expressed higher concentrations than fetal liver. Placental samples showed only a slight signal, with no change over the gestational range studied. In situ hybridization revealed the placental mRNA to be primarily associated with the decidua. Hepatic tissue showed specific binding to [125I]oGH and [125I]oPL from 51 days gestation. [125I]oPL showed a higher [51 days, 17.9 +/- 1.9% (mean +/- SEM); 95 days, 11.5 +/- 1.6%; 120 days, 16.3 +/- 0.9%] specific binding to the liver membranes than [125I]oGH (51 days, 2.1 +/- 0.7%; 95 days, 2.6 +/- 0.3%; 120 days, 3.5 +/- 0.4%). We conclude that oGHR are present as early as day 51 of gestation in various tissues, including liver. The message appears later in skeletal muscle than in liver. As the GH receptor binds oPL with higher potency than oGH, the parallel ontogenic changes in [125]oGH and [125]oPL binding in the liver do not support the presence of a PL receptor under independent developmental regulation. PMID- 8440173 TI - Ovarian follicular dominance in cattle: relationship between prolonged growth of the ovulatory follicle and endocrine parameters. AB - In cattle, the development of ovarian follicles 5 mm or larger occurs in either two or three consecutive follicular waves per estrous cycle. When the luteal phase is artificially lengthened with an intravaginal progesterone-releasing device (CIDR) that maintains subluteal levels (i.e. levels of progesterone that are below normal luteal levels, but higher than basal follicular phase levels), prolonged development of the ovulatory follicle is observed. To study the endocrinological correlates of prolonged follicular dominance and to test the hypothesis that it is mediated by effects of plasma progesterone on LH pulse frequency, heifers (n = 6/group) were treated with blank CIDRs (no progesterone, control group), with one CIDR for 14 days from day 14 of the cycle (1 CIDR group), or with one CIDR for 14 days from day 14 plus a second CIDR during days 24-28 (2 CIDR group). Cycle length was significantly longer in the 1 and 2 CIDR groups than in the controls (30.2 +/- 0.2 and 31.8 +/- 0.5 vs. 21.6 +/- 0.4 days, respectively; P < 0.0001). Follicular dynamics were normal in the control heifers. In the 1 CIDR group, the ovulatory follicle grew larger than in control or 2 CIDR animals, was maintained as the largest follicle on the ovaries for a much longer time, and ovulated after CIDR removal. In the 2 CIDR group, a similar growth pattern was observed until day 24; after insertion of a second CIDR, however, prolonged dominance was reversed, a new wave was recruited, and the dominant follicle of this wave ovulated after CIDR removal. The size of the ovulatory follicle and the length of the dominance phase in the 2 CIDR group were similar to those in control animals. Reversal of prolonged dominance in the 2 CIDR group was associated with changes in progesterone. Progesterone remained at subluteal levels (1.5-2.3 ng/ml) in both CIDR groups until day 24, when insertion of the second CIDR in the 2 CIDR group restored progesterone concentrations to normal luteal levels (3.5-6 ng/ml). Pulsatile LH secretion was assessed by frequent blood sampling every 12 min for 6 h (0800-1400 h) on selected days of the treatment cycle. LH pulse frequency was not different among groups before treatment started (days 12 and 13). However, LH pulse frequency was significantly higher in the 1 CIDR than in the 2 CIDR group on both day 26 (P < 0.03) and day 28 (P < 0.05), i.e. during the reversal of prolonged dominance in the 2 CIDR group.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8440174 TI - Primary structure and biological activity of a third gonadotropin-releasing hormone from lamprey brain. AB - Previous studies have led to the identification of two molecular forms of GnRH (GnRH-I and II) in the brain of the sea lamprey, Petromyzon marinus. From analysis of these two forms, the primary structure of GnRH-I and the amino acid composition of GnRH-II were determined. We have now isolated a third molecular form of GnRH (GnRH-III) from the brain of this species that is different from GnRH-I and -II. The primary structure of GnRH-III is pGlu-His-Trp-Ser-His-Asp-Trp Lys- Pro-Gly-NH2. A synthetic decapeptide with this amino acid sequence was chromatographically identical to natural GnRH-III. Intraperitoneal injection of synthetic lamprey GnRH-III (0.1 microgram/g) produced a significant (P < 0.05) elevation of plasma progesterone (31% over basal values) in female lampreys that was comparable to that produced by the same dose of lamprey GnRH-I (36% over basal). The elevation in plasma estradiol produced by lamprey GnRH-III (244% over basal) was significantly (P < 0.05) less than the elevation produced by GnRH-I (322% over basal). We propose based on the biological activity of lamprey GnRH III in these studies and the occurrence of this peptide during metamorphosis in lampreys, that both lamprey GnRH-I and -III are neurohormones involved in reproduction in lampreys. PMID- 8440175 TI - Ligand-binding properties of the two isoforms of the human insulin receptor. AB - Tissue-specific alternative splicing of exon 11 of the insulin receptor gene results in 2 mRNAs that differ by 36 nucleotides within the coding region. The 2 transcripts encode 2 protein isoforms with (Ex11+) or without (Ex11-) 12 additional amino acids at the carboxy-terminus of the receptor alpha-subunit. Previous studies of the 2 isoforms of the human insulin receptor expressed in mammalian cell transfectants have revealed small functional differences at the levels of equilibrium insulin binding affinity and acute ligand-induced receptor internalization. In the present study, we determined the biochemical basis for differential insulin binding affinity. Further functional characterization of the 2 receptor isoforms was also performed. The results obtained were as follows. 1) Studies of ligand association demonstrated a faster (1.8-fold) "on rate" for Ex11 receptors than for Ex11+ receptors, as determined by the kinetics of [125I]insulin binding to transfected cells. In addition, dissociation of prebound [125I]insulin from Ex11- receptors was characterized by an accelerated "off rate" relative to that of Ex11+ receptors. 2) Using both intact Chinese hamster ovary (CHO) cells and partially purified solubilized insulin receptors, the ability of insulin-like growth factor-I to compete for [125I]insulin binding to either isoform differed markedly. The mean IC50 for Ex11- was 40 nM vs. 350 nM for Ex11+. 3) Both Ex11- and Ex11+ receptors were equally capable of hybrid formation with endogenous CHO cell insulin-like growth factor-I receptors. 4) The relative abilities of 2 inhibitory polyclonal antiinsulin receptor antisera to displace [125I]insulin binding did not differ between the two isoforms. 5) Studies of insulin-induced (300 nM) receptor down-regulation in CHO cell transfectants suggested preferential down-regulation of Ex11- receptors; however, no down regulation difference was observed when Rat 1 cell transfectants expressing the two splice variants were studied. These findings further support the idea that the 2 isoforms of the insulin receptor are functionally distinct in important ways. PMID- 8440176 TI - Differential expression of insulin-like growth factor-I (IGF-I) and IGF-II messenger ribonucleic acid in growing rat bone. AB - Insulin-like growth factors (IGF-I and IGF-II) are among the most abundant growth factors found in bone. Although their local production has been implicated in growth and development, localization of the cells that express these proteins is not well documented. We have studied, by in situ hybridization, the temporal and spatial expression of IGF-I and IGF-II mRNA in rat long bones at different stages of postnatal bone development. In 2-day-old rats, IGF-II was highly expressed in cartilage and in the mesodermal structures that surround the bone. At later stages of bone development, the IGF-II signal decreased in intensity, but could still be detected in the growth plate of tibial bones at 3 and 5 weeks. At this stage, the IGF-II signal in the epiphyseal growth plate was unevenly distributed and was stronger in the periphery than in the center, where it was mainly concentrated in the germinal layer and in some, but not all, cartilage columns. IGF-I, on the other hand, was only faintly detected in the periosteum at the early cartilaginous stage of bone development. At later stages, IGF-I was strongly associated with regions of ossification in the trabecular bone of the metaphysis and epiphysis and along the endosteal and periosteal surfaces. Surprisingly, we did not detect at any time IGF-I mRNA in chondrocytes of the epiphyseal growth plate. These results suggest that in the rat, IGF-II plays a role in early development of bone and in the longitudinal growth of the epiphyseal plate. IGF-I is more closely associated with the osteogenic regions and does not replace the declining levels of IGF-II in the growth plate. PMID- 8440177 TI - Regulation of parathyroid hormone release by protein kinase-C is dependent on extracellular calcium in bovine parathyroid cells. AB - The purpose of this study was to evaluate regulation of PTH secretion by protein kinase-C (PKC) in adult bovine parathyroid cells. Extracellular calcium (Ca2+e) is the main physiological regulator of PTH secretion. Putative second messengers include intracellular calcium (Ca2+i), cAMP, inositol trisphosphate, and diacylglycerol (DAG). Both DAG and Ca2+i activate PKC. Certain phorbol esters mimic the effect of DAG and cause prolonged stimulation of PKC. The stimulatory phorbol esters 12-O-tetradecanoylphorbol acetate (1 microM) and phorbol-12,13 dibutyrate (1 microM) did not affect PTH secretion at low Ca2+e, but increased both individual cell secretion and recruitment of cells to secrete at high Ca2+e. The PKC inhibitors H7 (1 microM), tamoxifen (10 microM), and sphinganine (5 microM) inhibited PTH release at low Ca2+e (0.1 and 0.2 mM) and decreased cell recruitment over the physiological range of Ca2+e. The nonstimulatory phorbol esters 4 alpha-phorbol-12,13-didecanoate (1 microM) and phorbol-13-monoacetate (1 microM) had no effect on PTH secretion. To assess the mechanism by which certain phorbol esters stimulated PTH secretion, in situ hybridization for PTH mRNA was performed. Phorbol-12,13-dibutyrate (1 microM) qualitatively increased steady state PTH mRNA levels compared to control values. We conclude that 1) PKC stimulation increased PTH secretion at high Ca2+e, but not at low Ca2+e; 2) PKC inhibition decreased PTH secretion at low Ca2+e; and 3) PKC stimulation increased steady state PTH mRNA levels. These data suggest that PKC plays an important regulatory role in the synthesis and secretion of PTH. PMID- 8440178 TI - Transforming growth factor-beta 1 inhibits aldosterone biosynthesis in cultured bovine zona glomerulosa cells. AB - Transforming growth factors (TGF beta s) are emerging as possible autocrine regulators of steroidogenesis in a variety of steroid hormone-producing cells. Our laboratory has recently shown that TGF beta 1 is a potent inhibitor of basal and ACTH- and (Bu)2cAMP-stimulated aldosterone production. In this study, we investigated the effects of TGF beta 1 on potassium- and angiotensin-II (A-II) stimulated aldosterone and the mechanisms by which TGF beta 1 inhibits aldosterone biosynthesis. Cultured zona glomerulosa cells were incubated in serum free PFMR-4 medium in the presence and absence of TGF beta 1. To investigate the effects of TGF beta 1 on the early pathway of aldosterone biosynthesis, we studied the production of pregnenolone in the presence of the cyanoketone derivative WIN 19,578, which blocks the conversion of pregnenolone to progesterone. TGF beta 1 inhibited pregnenolone production from 133.9 +/- 30.1 to 68.7 +/- 25.4 ng/10(6) cells.h, and the ACTH-stimulated production of pregnenolone was inhibited from 764.6 +/- 127.7 to 141.0 +/- 2.2 ng/10(6) cells.h. In contrast, TGF beta 1 did not inhibit 25-hydroxycholesterol-stimulated pregnenolone production. To study the late pathway of aldosterone production, we added the steroid precursors deoxycorticosterone and corticosterone. TGF beta 1 significantly inhibited deoxycorticosterone- and corticosterone-stimulated aldosterone production by over 50%. TGF beta 1 inhibited the AII- and potassium induced synthesis of aldosterone. These observations show that TGF beta 1 inhibits AII- and potassium-induced aldosterone synthesis and the early pathway of aldosterone biosynthesis by interfering with the transport of cholesterol across the mitochondrial membrane as well as inhibiting the late pathway of aldosterone biosynthesis. PMID- 8440179 TI - Unimpaired postreceptor regulation of luteinizing hormone secretion by gonadotropin-releasing hormone and estrogen in aged rat anterior pituitary cells. AB - Delayed, attenuated, or absence of the proestrous LH surge occurs in aging rats. To assess how aging affects the positive feedback action of 17 beta-estradiol (E2) on the pituitary, we determined the responsiveness of rat pituitary cells to GnRH and the secretagogues affecting intracellular signal transduction mechanisms in the presence or absence of E2. We also correlated the LH response to pituitary LH content. Anterior pituitaries excised from ovariectomized Sprague-Dawley rats, either young (3-4 months) or old (19-20 months), were enzymatically dispersed and then pretreated with or without E2 (0.6 nM) for 48 h, followed by incubation for 3 h with or without various secretagogues. The secretagogues included GnRH (1 and 10 nM), veratridine (increases Ca2+ influx; 5 and 10 microM), and phorbol 12 myristate 13-acetate (a protein kinase-C activator; 10 and 100 nM). LH in media and cells were measured by RIA and expressed on the basis of cellular DNA. GnRH, veratridine, and phorbol 12-myristate 13-acetate at all doses stimulated (P < 0.01) LH release in cells from both young and old rats. E2 stimulated (P < 0.05 to P < 0.01) all secretagogue-induced LH release in cells from both young and old rats, but only basal LH release (P < 0.05) in cells from young rats. The magnitude of both basal and secretagogue-induced LH release in either the presence or absence of E2 was smaller (P < 0.01) in cells from old than in those from young rats. The initial cellular LH was lower (P < 0.01) in cells from old than in those from young rats. The LH-releasing ability (expressed as a percentage of total cellular LH) of cells from old rats was identical (P > 0.05) to that of cells from young rats under all conditions studied. These results suggest that the reduced magnitude of LH release by cells from old rats may be attributed to reduced cellular LH, rather than to impaired estrogen feedback or impaired signal transduction mechanisms. It remains to be determined whether LH biosynthesis per cell and/or the number of gonadotropes decrease with age. PMID- 8440180 TI - Iodothyronine 5'-deiodinase is present in mouse sublingual gland. AB - Homogenates from male ddy mouse sublingual glands were incubated with 100 nM [125I]rT3 in the presence of 2 mM dithiothreitol (DTT). Metabolites were analyzed by HPLC or Dowex-50 minicolumn assay. 3,3'-Diiodothyronine and I- were the only appreciable products. Iodide release from rT3 was compatible with the enzymatic nature. The Km and maximum velocity from three separate determinations were 326, 356, and 629 nM and 29.8, 42.1, and 31.3 pmol I- release/mg protein.min, respectively. The deiodinase activity was DTT dependent and had higher affinity for rT3 than for T4 or T3. 6-Propyl-2-thiouracil inhibited the deiodination, which was competitively overcome by DTT. Sublingual 5'-deiodinase activity was approximately 80% of that in the liver, while the submandibular gland showed no deiodination. Our results show the presence of 5'-deiodinase (type I) in mouse sublingual gland for the first time. Selective localization and abundance of the enzyme suggest a previously unrecognized role of the sublingual gland in thyroid hormone physiology. PMID- 8440181 TI - A role for heparan sulfate in androgen-induced deoxyribonucleic acid synthesis of mouse mammary carcinoma (Shionogi carcinoma 115)-derived SC-3 cells. AB - In response to androgen stimuli, SC-3 cells cloned from mouse mammary carcinoma (Shionogi carcinoma 115) secrete heparin-binding growth factor, which is able to bind to fibroblast growth factor (FGF) receptor, ultimately resulting in SC-3 cell proliferation. A role for glycosaminoglycan in the process of this androgen induced autocrine loop was examined. When quiescent SC-3 cells were stimulated with testosterone, enhanced DNA synthesis was demonstrated even at the early phase (12-24 h) of stimulation. During this early period, autocrine growth promoting activity was found to be associated with cell surface and extracellular matrix, but not to be present in the conditioned medium. This bound form of growth-promoting activity was able to be extracted with 2 M NaCl (pH 7.5) and absorbed onto a heparin-Sepharose affinity column, from which it was eluted at a concentration of 1.1-1.3 M NaCl. Extracted growth factor, whose activity was partially blocked by anti-basic FGF antibody, up-regulated the expression of FGF receptor-1 mRNA. These characteristics were similar to those of a soluble form of SC-3-derived growth factor previously reported from our laboratory. Androgen induced enhancement of DNA synthesis was inhibited by simultaneous treatment of SC-3 cells with 10 mIU/ml heparitinase or 25 mM sodium chlorate (an inhibitor of phosphoadenosine sulfate synthesis). However, chlorate treatment did not affect the synthesis and distribution of androgen-induced growth factor, suggesting that the response of chlorate-treated cells to this growth factor was impaired. These results indicate that heparan sulfate has important roles in concentrating androgen-induced heparin-binding growth factor on or very close to the cell surface and in potentiating its bioactivity. PMID- 8440182 TI - Neural cell adhesion molecules in rat endocrine tissues and tumor cells: distribution and molecular analysis. AB - The adhesive properties of neural cell adhesion molecules (NCAMs) can be modified by alternative splicing of the primary transcript or posttranslational modifications. In the present study, we describe distinct forms of alternative splicing and posttranslational modification of the extracellular domain of NCAM of various endocrine tissues and derived tumor cells of the rat. Using an antiserum detecting the immunoglobulin-like domains of NCAM as well as a monoclonal antibody recognizing the NCAM-specific polysialic acid (PSA), we observed a similar staining pattern in adrenals, pituitary, and neoplastic endocrine cells. In endocrine tumor cells [pheochromocytoma (PC12), insulinoma (RINA2), and pituitary tumor cells (GH3)], NCAM immunoreactivity was most intense at contact sites between the cells. The immunocytochemical data were substantiated by results of in situ hybridization histochemistry. Specifically, higher levels of NCAM mRNA were detected in the adrenal cortex than in the medulla. In the pituitary, NCAM mRNA was more abundant in the anterior and intermediate lobes than in the neural lobe. The sequence of NCAM mRNAs in endocrine cells was analyzed by polymerase chain reaction and S1 nuclease protection assays. We found that major exons 4-13 of the NCAM mRNA in endocrine tissues and related tumor cell lines were homologous to those in the brain. However, PC12, RINA2, and GH3 tumor cells; normal rat pituitaries; and adrenals contained different amounts of NCAM mRNA with an alternative extra exon, termed VASE (also called pi in mouse) between constitutive exons 7 and 8. In addition, in pituitaries, we detected an alternative exon in splice site a between the constitutive exons 12 and 13, termed a15, with or without an AAG triplett. These sites are thought to be important for the adhesive properties of NCAM. Therefore, these results suggest that modifications of NCAM may be important for adhesive interactions in normal and neoplastic endocrine cells. PMID- 8440183 TI - Osmolality and potassium cause alterations in the volume of glomerulosa cells. AB - Alterations in extracellular osmolality have a powerful inverse effect on aldosterone secretion and potassium- and angiotensin-stimulated aldosterone secretion. Whether alterations in extracellular osmolality produced sustained changes in cell volume that may contribute to the regulation of aldosterone secretion is not known. Using dispersed bovine glomerulosa cells grown in primary culture, the effect of alterations in osmolality on cell volume, measured by the distribution of [14C]urea and [3H]inulin and videometric analysis of the surface area of glomerulosa cells, was determined. Alterations in osmolality had an inverse effect on cell volume and surface area. Changes in cell volume induced by exposure to anisotonic medium were 52% greater (P > 0.02) than that predicted by the changes in osmolality. Increases in potassium concentration also caused sustained (1-h) concentration-dependent increases in cell volume and surface area. Angiotensin-II did not increase glomerulosa cell volume, but did produce a small dose-dependent transient increase in cell surface area. The results demonstrate that alterations in osmolality do cause sustained changes in cell volume, and thus, membrane stretch could be an important part of the cellular mechanism responsible for causing osmolality-induced changes in the cytosolic calcium concentration and subsequent alterations in aldosterone secretion. Alterations in membrane stretch may also be an important component of potassium induced, but not angiotensin II-induced, aldosterone secretion. PMID- 8440184 TI - Plasma and cerebroventricular fluid levels of pancreatic polypeptide in the dog: effects of feeding, insulin-induced hypoglycemia, and physical exercise. AB - We investigated the penetration of plasma pancreatic polypeptide (PP) into the third cerebral ventricular fluid (CSF) of dogs. Plasma and CSF levels of PP were measured by RIA during the iv infusion of PP and during such stimuli as eating, insulin-induced hypoglycemia, and physical exercise. Plasma and CSF levels of insulin and glucose were also measured and compared during eating and insulin induced hypoglycemia. Plasma glucose increased after feeding and decreased after insulin injection, followed by a corresponding change in CSF glucose without an apparent time lag. CSF insulin insignificantly increased after feeding and the injection of insulin, while CSF PP did not increase despite the marked elevation of plasma PP in response to these stimuli. CSF PP did not increase after the infusion of exogenous PP. Strenuous exercise, however, evoked an increase in both plasma and CSF PP levels; the CSF response was prompt, but more prolonged than that of plasma, suggesting the slow removal of PP from CSF. We conclude that 1) PP and insulin in CSF do not appear to play a major role in the short term regulation of food intake and acute changes in energy metabolism; and 2) PP, probably after entering the brain, may modulate brain function in such physiological situations as strenuous exercise. PMID- 8440185 TI - Uterine luteinizing hormone/human chorionic gonadotropin-binding sites in the early pregnant rat uterus: evidence for total occupancy in the periimplantation period. AB - We have investigated the presence of high affinity LH/hCG-binding sites (RLH) in crude membranes from early pregnant rats uteri. The uterine concentration of available RLH increased from day 1 to day 3 (1.3 +/- 0.2 vs. 2.8 +/- 0.4 fmol/mg protein) without a change in the affinity constant (approximately 5 x 10(10) M 1). However, unoccupied uterine RLH disappeared in the periimplantation period (days 4-6). To determine if the drop in available RLH was consecutive to their occupancy, uterine membranes were treated with acidified medium (25 mM Tris-HCl, and 5 mM MgCl2, pH 2.5) to remove endogenous ligand. The number and affinity of total (occupied plus available) RLH in acid-eluted membranes were estimated by Scatchard analysis of [125I]hCG binding and compared with those of available RLH in untreated membranes from the same uterine preparation. The uterine concentration of total RLH increased first between days 1 and 2 (2.2 +/- 0.5 vs. 4.2 +/- 0.8 fmol/mg protein), then between days 3 and 4 (4.2 +/- 0.6 vs. 6.5 +/- 0.8 fmol/mg protein), before plateauing until day 6. Thus, the reduction in the available uterine RLH in the periimplantation period is largely due to occupancy, rather than down-regulation, of RLH. The occupancy of uterine RLH 1) increased during early pregnancy (day 1, approximately 20%; days 2-3, approximately 40%; days 4-6, approximately 100%), 2) paralleled the increase in total RLH number, and 3) was probably due to pituitary LH only. However, the blastocyst itself seemed to influence uterine RLH occupancy, since available uterine RLH were detected on day 5 of pseudopregnancy. The increase in total uterine RLH as well as the perfect synchrony between their occupancy and the previously described pattern of uterine cAMP concentration during rat early pregnancy suggest that the response of uterine (and more precisely luminal epithelium) adenylate cyclase to LH (and/or related substance originating from embryo) may determine uterine receptivity for ovoimplantation and subsequent decidualization. PMID- 8440186 TI - Differential localization of the 5 alpha-reductase and the 3 alpha-hydroxysteroid dehydrogenase in neuronal and glial cultures. AB - The activities of the 5 alpha-reductase [the enzyme that converts testosterone into dihydrotestosterone (DHT)] and 3 alpha-hydroxysteroid dehydrogenase [the enzyme that converts DHT into 5 alpha-androstan-3 alpha, 17 beta-diol (3 alpha diol)] have been evaluated in primary cultures of neurons, oligodendrocytes, and type 1 and 2 astrocytes obtained from fetal or neonatal rat brain. All cultures were used on the fifth day. The formation of DHT and 3 alpha-diol was evaluated by incubating the different cultures with [14C]testosterone or [14C]DHT as substrates. The results obtained indicate that the formation of DHT takes place preferentially in neurons; however, type 2 astrocytes and oligodendrocytes also possess considerable 5 alpha-reductase activity, while type 1 astrocytes show a much lower enzymatic activity. A completely different localization was observed for 3 alpha-hydroxysteroid dehydrogenase. The formation of 3 alpha-diol appears to be mainly, if not exclusively, present in type 1 astrocytes. 3 alpha-Diol is formed in very low yields by neurons, type 2 astrocytes and oligodendrocytes. The compartmentalization of two strictly correlated enzymes (5 alpha-reductase and 3 alpha-hydroxysteroid dehydrogenase) in separate central nervous system cell populations suggests the simultaneous participation of neurons and glial cells in the 5 alpha-reductive metabolism of testosterone and possibly other hormonal steroids (e.g. progesterone, corticoids, etc.). PMID- 8440187 TI - Identification of the thyrotropin-releasing hormone-prohormone and its posttranslational processing in a transfected AtT20 tumoral cell line. AB - By using an AtT20 cell line transfected with complementary DNA for preproTRH, we have identified the proTRH polyeptide precursor [26 kilodaltons (kDa)] and shown that this molecule gives rise to the proTRH derived sequences as determined by pulse-chase and trypsinization studies. The predicted proTRH precursor composed of 231 amino acids with 5 copies of a TRH progenitor sequence (Gln-His-Pro-Gly) and 7 other cryptic peptides was demonstrated by: 1) Western Blot analysis of an AtT20 cell extract with anti-pCC10 antibodies (an antibody that recognizes the intact prohormone as well as some intermediate products of processing); 2) Immunoprecipitation of the radiolabelled 26 kDa protein with anti-pCC10 followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis; 3) Gel filtration chromatography of the radiolabeled 26 kDa extracted from SDS PAGE. 4) RIA with anti-pCC10 antiserum against peptides extracted from adult rat hypothalamus and olfactory lobe after SDS-PAGE. 5) Trypsinization of the proTRH precursor which generated the proTRH cryptic peptides preproTRH25-50 (pYE27) and preproTRH53-74 (pFT22). These moieties were also produced during trypsinization of intermediate products of processing. By means of pulse-chase studies, the 26 kDa polypeptide was shown to be the biosynthetic precursor to all the proTRH derived cryptic peptides. Cleavage at two positions in the center of the molecule (Lys107-Arg108 and Lys152-Arg153) generated two moieties of 16.5 and 15 kDa. The 15 kDa N-terminal fragment is later cleaved to a 6 kDa peptide that includes the proTRH derived peptides, pYE27, pFT22, and pEH24. The carboxy-terminal 16.5 kDa fragment of the prohormone is processed to a 9.6 kDa fragment which contains the proTRH derived peptide pST10 (preproTRH160-169) and a fragment of 5.4 kDa that may be the C-terminal peptide preproTRH208-255 recognized by antisera pAC12 and pYE17. In further processing, the 9.6 kDa molecule is cleaved to produce a 5.4 kDa peptide from either sequences 115-169 or 160-199. PMID- 8440188 TI - Processing of proTRH to its intermediate products occurs before the packing into secretory granules of transfected AtT20 cells. AB - The intracellular compartments where posttranslational processing of proTRH takes place have not been identified. Using AtT20 cells transfected with a complementary DNA for preproTRH, we have used purified antibodies that recognize the intact precursor, intermediate and end products of processing to identify the subcellular compartments in which cleavage occur. Further, pulse-chase experiments followed by subcellular fractionation were undertaken to determine the order of processing of proTRH during its transport to the secretory granules. Cells were homogenized by nitrogen cavitation and subjected to a centrifugation of 1.065 mg/ml density gradient of Percoll to separate secretory granules (SG) from rough endoplasmic reticulum (RER)/Golgi apparatus. The purity of the SG and RER fractions was assessed by assays of marker enzymes for mitochondria, RER, Golgi, and cytoplasm. ProTRH derived cryptic peptides and TRH in each fraction were determined by RIA. Golgi and SG fractions were subjected to polyacrylamide gel electrophoresis followed by extraction and RIA. Using the anti-pCC10 antiserum which recognizes intact (26 kd) as well as partially processed prohormone, the RER/Golgi fraction contained 0.3 pmol intact ProTRH and 0.2 pmol each 15 and 6 kilodalton (kDa) fragments; the SG contained the 15 kDa moiety (0.2 pmol) along with a 6 kDa (0.4 pmol) material but not the 26 kDa ProTRH. The SG were also enriched by 0.21 pmol pYE27 (PreproTRH 25-50), 0.23 pmol pFT (PreproTRH 53-74), 0.31 pmol pEH24 (PreProTRH 86-106), and 0.5 pmol TRH. None of these were present in the RER/Golgi. Pulse-chase studies also showed that the intact proTRH (26 kDa) precursor was only present in the RER/Gg fraction along with two of its N-terminal intermediate processing products, a 15 k mol wt peptide and a 6 k mol wt peptide, and two of its C-terminal processing products, a 16.5 k mol wt and a 9.6 k mol wt peptides. In addition, fully processed peptides as well as TRH were only detected in the neurosecretory granules. These observations suggest that after the initial conversion of proTRH in the RER/Golgi fraction, the peptides are delivered to the granules where processing to TRH and cryptic peptides takes place. Supporting this, our pulse-chase studies unequivocally showed that, pEH24, an end product of proTRH processing, was only produced in secretory granules. Thus, initial cleavage of the TRH precursor may be required for packing and sorting of the end products to occur. PMID- 8440190 TI - Melatonin and its analogs inhibit the basal and stimulated release of hypothalamic vasopressin and oxytocin in vitro. AB - The secretion of neurohypophyseal hormone and ACTH in the rat has been shown to exhibit circadian rhythms, with high values during the day and low values throughout the night. The neurohypophyseal hormone daily rhythm is altered by exposure to constant light and by pinealectomy. It was, thus, proposed that the observed fall in vasopressin (AVP), oxytocin, and ACTH over the hours of darkness could be related to the release of melatonin seen at this time. Therefore, a study was performed to determine the effect of melatonin on AVP, oxytocin, and CRH-41 release from the isolated rat hypothalamus in vitro. Employing a previously validated technique, rat hypothalami were incubated in either medium alone or medium containing melatonin or one of two melatonin analogs. Hormone release was measured by RIA, and the ratios were calculated and compared by Student's t test, with Dunnett's correction for multiple comparisons. Melatonin showed a dose-dependent inhibition of both basal and stimulated AVP and oxytocin release in the concentration range 4.3 x 10(-10) to 2.5 x 10(-3) M, while having no significant effect on the release of CRH-41. The two melatonin analogs, 2 iodomelatonin and 5-methoxy-N-isobutanoyltryptamine, were also found to inhibit both basal AVP and oxytocin release, indicating that this effect probably depends upon the presence of melatonin receptors in the hypothalamus. This inhibitory modulation of AVP, in the absence of any effect on CRH-41, suggests that melatonin may affect water balance by means of directly inhibiting hypothalamic AVP release. Furthermore, circadian rhythmicity in pituitary-adrenal activity may depend on melatonin modulation of AVP, rather than changes in CRH-41. PMID- 8440189 TI - Evidence for carrier-mediated uptake of triiodothyronine in cultured anterior pituitary cells of euthyroid rats. AB - T3 uptake and TSH secretion were investigated in anterior pituitary cells isolated from adult fed Wistar rats and cultured for 3 days in medium containing 10% fetal calf serum. TSH release during culture increased linearly with the number of cells in the range of 80,000-800,000 cells/well. Uptake and incubation experiments were performed at 37 C in medium containing 0.5% BSA. Incubation with TRH (0.1 microM) for 2 h stimulated TSH release 2.6-fold, and this effect was partly (approximately 45%) suppressed by preexposure for 2 h to T3 (0.01-1 microM) or T4 (1 microM). Similar concentrations of T3 and T4 reduced the cellular uptake of [125I]T3 (50 pM) during 1 h of incubation by 55%. After 15 min of incubation, [125I]T3 uptake (percent dose) amounted to 1.26 +/- 0.05% (mean +/ SE; n = 9)/500,000 cells. The major part (75%) of the [125I]T3 was found in the extranuclear fraction. Simultaneous incubation with unlabeled T3 (1 or 10 microM) reduced [125I]T3 uptake by 43% (n = 3; P < 0.001) and 52% (n = 6; P < 0.001), respectively. Reduction of the temperature to 20 C diminished the T3-suppressible fraction of [125I]T3 uptake approximately 3-fold. After preincubation (30 min) and incubation (15 min) with monodansylcadaverine (100 microM), the uptake of [125I]T3 was reduced by 32% (n = 3; P < 0.01). When the Na+ gradient was reduced by preincubation and incubation with ouabain (0.5 mM) or monensin (10 or 100 microM), T3 uptake was inhibited by 25% (n = 5; P < 0.01), 37% (n = 6; P < 0.001), and 61% (n = 3; P < 0.001), respectively. It is concluded that 1) T3 is taken up by the pituitary by a carrier-mediated mechanism, and 2) this uptake is at least partly dependent on the Na+ gradient. PMID- 8440191 TI - The effect of leukemia inhibitory factor on bone in vivo. AB - The local effects of leukemia inhibitory factor (LIF) on bone turnover in vivo have been examined. Recombinant murine LIF (0.2 micrograms) or vehicle was injected daily for 5 days over the right hemicalvaria, and the mice were killed on day 6 or 13. Effects on calvarial bone morphology were assessed using quantitative histomorphometry of nondecalcified bone tissue. Increased bone resorption was present in LIF-treated hemicalvaria compared with that in the noninjected hemicalvaria or calvaria from mice injected with vehicle alone at both 6 and 13 days. Significant increases in LIF-treated animals were as follows. Eroded surface increased 10-fold (P = 0.022), osteoclast surface increased 5-fold (P = 0.003), osteoclast numbers increased 3-fold (P = 0.002), and the number of osteoclast nuclei increased 3-fold (P = 0.009). Fibrotic tissue was laid down in the resorption defects, and there was an accompanying thickening of the periosteum (3 times greater in LIF-injected animals; P = 0.003), causing the overall thickness of the treated bones to be almost doubled (P = 0.045). Indices of bone formation were increased in animals treated with LIF. Osteoblast numbers, osteoblast surface, and osteoid area were doubled (P = 0.012, 0.016, and 0.058, respectively). Similar effects of LIF were seen in indomethacin-treated animals. Small but statistically significant morphological changes were also seen in the left noninjected hemicalvariae when LIF-treated animals were compared to controls. LIF increased periosteal area (P = 0.01) and total mineralized bone area (P = 0.002). In conclusion, LIF accelerated bone turnover locally in a prostaglandin-independent manner in normal mice, demonstrating its potential to modify in vivo bone cell function dramatically. PMID- 8440192 TI - Synthesis and release of calcitonin-like immunoreactivity by anterior pituitary cells: evidence for a role in paracrine regulation of prolactin secretion. AB - Calcitonin (CT) is a potent and specific inhibitor of basal and TRH-induced PRL release and PRL mRNA levels in rat anterior pituitary (AP) cells, an action mediated through specific inhibition of the Ca(2+)-inositol phosphate messenger system. Because CT and CT-like peptides have been reported to be present in the AP, the present studies investigated 1) whether 35S-labeled CT-like substances can be precipitated from rat AP cell lysates, 2) whether immunoreactive CT is secreted from rat AP cells, as assessed from a cell blot assay and from RIA of spent medium from cultured AP cells, and 3) whether the release of PRL from cultured rat AP cells can be influenced by immunoneutralization of endogenous CT. Dispersed rat AP cells were labeled with [35S]cysteine, CT-like substances were immunoprecipitated from the lysate with antihuman CT (anti-hCT) and antisalmon CT (anti-sCT) immunoglobulin G conjugated to protein-A-Sepharose beads, and the immunoprecipitates were fractionated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and identified by fluorography. The results revealed that both anti-sCT and anti-hCT sera precipitated three major bands of 35S-labeled material from AP cell lysates, with approximate molecular masses of 23, 6.5, and 3.5 kilodaltons. Synthetic sCT completely displaced anti-sCT-precipitable bands and partially displaced anti-hCT precipitates. The cell blot assay revealed the presence of CT-immunopositive AP cells, and secretion of this substance was indicated by zones of secretion surrounding these cells. Immunoreactive CT was also detected in spent medium from cultured rat AP cells, and the average rate of release over 4 days of culture was approximately 1 ng sCT eq/3 million AP cells.24 h. Both anti-sCT and anti-hCT sera significantly stimulated PRL release from rat AP cells, and the stimulatory effect of anti-sCT serum was dose dependent up to a concentration of 1:50. The present findings demonstrate that CT like peptide(s) is synthesized and released from cultured AP cells and suggest that this peptide may participate in the regulation of PRL secretion via paracrine or autocrine actions. PMID- 8440193 TI - Estrogen modulation of avian osteoclast lysosomal gene expression. AB - We have previously demonstrated that avian osteoclasts contain high levels of 17 beta-estradiol (17 beta E2) receptors and respond to 17 beta E2 treatment with a dose-dependent decrease in in vitro resorption of [3H] proline-labeled bone particles. To more accurately assess the influence of 17 beta E2 on osteoclastic activity, the specificity of estrogen modulation of resorption levels was determined using a quantitative pit resorption assay. Treatment with 17 beta E2 significantly decreased the number of osteoclast resorption pits formed compared with that after either vehicle or 17 alpha E2 treatment. Cotreatment with 17 beta E2 and hydroxytamoxifen (a complete 17 beta E2 antagonist in birds) abrogated the influence of 17 beta E2 on resorption activity. To elucidate the mechanism by which 17 beta E2 inhibits osteoclast activity, the effects of 17 beta E2 on the steady state mRNA levels of two avian osteoclast lysosomal proteins, lysozyme and a lysosomal membrane protein (LEP-100), were examined. Using highly purified avian osteoclasts, 17 beta E2 was shown to decrease lysosomal protein mRNA levels in a dose-dependent manner within 8 h of treatment in a process that required de novo protein synthesis. This response was specific for 17 beta E2, since the inactive stereoisomer 17 alpha E2 had no effect. Furthermore, coincubation of 17 beta E2 with hydroxytamoxifen eliminated the 17 beta E2 influence. After removal of 10(-8) M 17 beta E2, lysosomal gene mRNA levels returned to near-normal levels within 24 h. This is consistent with the previously reported ability of avian osteoclast-mediated resorption activity to recover from 17 beta E2 treatment. Lysozyme protein levels similarly decreased after 17 beta E2 treatment. These data suggest that avian osteoclasts are target cells for 17 beta E2 in vitro, that osteoclast activity in vivo is likely to be modulated by circulating levels of 17 beta E2, and that the 17 beta E2 inhibition of osteoclast resorption activity may be mediated at least in part via regulation of osteoclast lysosomal gene expression. PMID- 8440194 TI - Germ cells of the mouse testis express P450 aromatase. AB - Estrogen production within the testis has been a subject of considerable controversy for many years. Several studies have shown that both Sertoli and Leydig cells produce estrogen during different stages of development. Therefore, we have conducted experiments to localize aromatase, a cytochrome P450 enzyme that converts androgen to estrogen, within the testis. First, P450 aromatase (P450arom) was localized in germ cells of the adult mouse testis by immunocytochemistry, using an antiserum generated against purified human placental cytochrome P450arom. In the germinal epithelium, P450arom was located primarily in the Golgi region of round spermatids, throughout the cytoplasm of elongating spermatids, and along the flagella of late spermatids. Second, localization of P450arom within the germinal epithelium was supported by Western blot analysis of isolated germ cells. Third, Northern blot analysis using a mouse P450arom cDNA probe indicated that the mRNA for the mouse P450arom was present in testicular germ cells. Fourth, P450arom activity was measured in germ cells by the 3H2O water assay. Based upon these observations, we conclude that germ cells are a site of estrogen synthesis in the adult mouse testis. PMID- 8440195 TI - Inhibition of osteoclastic bone resorption in vivo by echistatin, an "arginyl glycyl-aspartyl" (RGD)-containing protein. AB - Osteoclastic bone resorption requires the formation of a tightly sealed compartment between the osteoclast and the mineralized bone matrix. This compartment functions as an extracellular "lysosome" which contains proteolytic enzymes and acids. Vitronectin receptors (VnR, integrin alpha v beta 3) displayed on the osteoclast cell surface may play a role in the attachment of osteoclasts to the resorption surface. VnR are known to bind to arginyl-glycyl-aspartyl (RGD) containing matrix proteins and it has recently been reported that soluble peptides containing RGD sequences can block osteoclast attachment to bone and inhibit bone resorption in vitro. In this study echistatin, a naturally-occurring protein containing an RGD-sequence motif, was shown to completely inhibit osteoclast-mediated bone resorption in vivo. Echistatin or smaller derivative peptides may prove useful in the treatment of disorders characterized by excess bone resorption, such as osteoporosis and metastatic bone disease. PMID- 8440196 TI - Echistatin, a potential new drug for osteoporosis. PMID- 8440197 TI - Role of glucocorticoids in the regulation of brain prostaglandin biosynthesis under basal conditions and in response to endotoxin. AB - Glucocorticoids (GC) are known to inhibit eicosanoid production in various peripheral tissues; however, their role in the regulation of basal and induced prostaglandin (PG) biosynthesis in the brain is still not clear. In the present study we examined the effect of exogenous dexamethasone (dex) or endogenous GC on basal and on bacterial endotoxin (lipopolysaccharide, LPS) induced ex vivo production of PGE2 by the frontal cortex of rat brain. The experimental groups were: 1) intact rats; 2) rats in whom endogenous GC were removed either by surgical or by chemical (metopirone) adrenalectomy (adex); and 3) rats exposed to specific corticosteroid receptor antagonists. In intact rats, the basal rate of PGE2 ex vivo synthesis was about 120 pg/mg protein.hr; dex (0.05-0.5 mg/100 g body wt ip) did not affect this level. Exposure to LPS (50 micrograms, intracerebroventricular) induced a 2-fold increase in PGE2, whereas pretreatment with dex abolished this increase. Bilateral adex or metopirone alone did not change PGE2 synthesis, whereas LPS administration to surgical or chemical adex rats resulted in a 4-fold increase in PGE2 production. Administration (intracerebroventricular) of either one or both of the specific corticosteroid receptor antagonists, RU-28318 (type I) and RU-38486 (type II) did not affect basal PGE2 production. When LPS was given after either one of these antagonists, a slight but significant elevation of PGE2 occurred, as compared to LPS-treated controls. When both antagonists were coadministered, the LPS-induced production of PGE2 was much more pronounced, similar to levels of LPS-treated, adex rats. These results suggest that LPS-induced production of PGE2, but not the basal production, is regulated by either endogenous or exogenous GC, and the inhibitory effect of GC on brain PG synthesis is mediated via both type I and II corticosteroid receptors. PMID- 8440198 TI - Serum factors induce messenger ribonucleic acid levels for cellular retinol binding protein in rat Sertoli cells. AB - This report shows that serum factors dramatically increase the levels of mRNA for cellular retinol-binding protein (CRBP) in cultured rat Sertoli cells. Incubation of rat Sertoli cells (0-24 h) with 10% fetal calf serum (FCS) was associated with a time-dependent increase in CRBP mRNA levels. A significant increase (6-fold) was observed after 3 h of incubation. Maximal levels (15- to 50-fold) were reached after 9-12 h and were maintained for as long as serum was present. The effect was concentration dependent, with maximal induction at 10% FCS. Removal of FCS resulted in a decline in the CRBP mRNA levels, with a t1/2 of approximately 7 h. The CRBP mRNA stimulating activity (CMSA) was completely removed from FCS by precipitation with 5% trichloroacetic acid, but was only partly (50%) inhibited by heating at 100 C or trypsin treatment. Removal of retinol from FCS by repeated ether extractions did not alter the CMSA of FCS. Both the induction and degradation of CRBP mRNA were inhibited by the protein synthesis inhibitor cycloheximide. A nuclear protein binding to the 5'-flanking region of the CRBP gene was detected in nuclear extracts from untreated Sertoli cells, but not in nuclear extracts from Sertoli cells treated with 10% FCS for 3 h. Thus, serum factors, different from retinoids, dramatically stimulate the levels of CRBP mRNA in rat Sertoli cells. This is associated with the loss of protein binding to the 5'-flanking region of the CRBP gene. PMID- 8440199 TI - Impaired peripheral thyroid hormone metabolism in genetic obesity. AB - The obese Zucker rat has alterations in thyroid hormone metabolism resulting in a lower serum T3 concentration and T3 plasma appearance rate compared to its lean littermates. This study was undertaken to measure the contribution of specific nonthyroidal tissues to the total production of T3 in vivo in the Zucker fatty rat. Simultaneous pulse kinetic studies of T4 and T3 were performed in lean and obese Zucker littermates and analyzed according to a three-pool model of distribution and metabolism. The serum concentration and plasma appearance rate of T3 were both decreased in the obese vs. lean Zucker phenotype (P < 0.05) despite an elevated serum concentration and plasma appearance rate for T4. The quantity of T4 within the fast pool (i.e. liver and kidney) available for deiodination was equal for both phenotypes; however, generation of T3 within the fast pool was impaired for the obese compared to the lean group (-25%; P < 0.05). The tissue content of radiolabeled T3 generated within the liver 24 h post injection of T4 for the obese group was 48% lower (P < 0.02) vs. the lean group. A separate group of lean and obese littermates were surgically thyroid-ectomized and replaced with T4 to maintain a euthyroid state. The obese Zucker group had lower serum T3 concentrations and T3 plasma appearance rates compared to similarly treated lean Zucker animals despite similar T4 serum concentrations. Treatment with propylthiouracil produced a decline in serum T3 plasma appearance rate T3 PAR (-55%; P < 0.02) in the T4-replaced lean rat but no alteration in T3 metabolism in the fatty Zucker rat. We conclude that the obese Zucker rat has impaired T3 synthesis in tissues containing Type I 5-deiodinase despite adequate T4 availability as substrate for deiodination to T3. PMID- 8440200 TI - Pulmonary effects of chronic exposure to liposome aerosols in mice. AB - Administering liposome-encapsulated drugs by aerosols could be a feasible way of targeting drugs to the lung, specifically to pulmonary alveolar macrophages (AM). In the mouse model, we characterized uptake of carboxyfluorescein- (CF-) labeled liposomes by AM in vivo after acute inhalation of liposome aerosols, and the effects of chronic exposure to liposome aerosols on lung histology and AM function. Mice were placed in a nose-only exposure module and exposed to liposome or saline aerosols for 1 h per day, 5 days per week, for 4 weeks. Five mice of both the experimental and control groups were removed weekly and their lungs examined. Liposomes were made from hydrogenated soy phosphatidylcholine (HSPC) at 50 mg/mL. In vivo uptake of liposomes by AM was documented by fluorescence microscopy and flow cytometry of bronchoalveolar lavage (BAL). A consistent amount of 1-3 micrograms of lipid inhaled per dosing per mouse was estimated from fluorescence measurements. Addition of Triton X-100 to BAL caused a significant increase in fluorescence intensity, indicating that liposomes remained intact in the lung for a period of time. The chronic inhalation study showed no histologic changes of the lung or untoward effects on the general health or survival of animals. AM phagocytic function, intracellular killing, and fatty acid composition were not affected. Transmission electron microscopy and morphometry (computerized image analysis) of AM likewise showed no alterations as a result of the treatment. It was concluded that AM uptake of liposomes delivered by aerosol was operant in vivo. This finding validates the concept of alveolar macrophage directed delivery of liposome-encapsulated agents to the lung via inhalation. It was also concluded that chronic liposome aerosol inhalation in mice produced no untoward effects on survival, histopathology, and macrophage function. These data confirm and extend prior findings regarding the functional and morphologic interactions of liposomes with AM in vitro (Gonzalez-Rothi et al., Exp. Lung Res. 17:687-705, 1991). PMID- 8440201 TI - Dual effect of nitrogen dioxide on rat alveolar macrophage arachidonate metabolism. AB - Significant deficits in alveolar macrophage (AM) function have been associated with acute exposure to nitrogen dioxide (NO2). The present investigation examined changes in enzymatic production of arachidonate metabolites from rat AM exposed to NO2. While in vitro exposure of AM to NO2 concentrations between 0.1 and 5 ppm alone had small effects on basal synthesis of cyclooxygenase or lipoxygenase products, exposure to either 1 ppm (2 or 4 h) or 5 ppm (1 h) markedly enhanced the response of AM to stimulation by the calcium ionophore, A23187. This pre exposure led to significant increases in cyclooxygenase products (thromboxane B2 (thromboxane), the stable metabolite of thromboxane A2, and 12 hydroxyheptadecatrienoic acid (12-HHT)) and lipoxygenase products (leukotriene B (LTB4) and monohydroxyeicosatetraenoate isomers) in response to A23187. In contrast, a 1-h exposure to 20 ppm NO2 alone significantly increased AM synthesis of thromboxane and 12-HHT, but suppressed the effect of subsequently added A23187. Increased synthesis of cyclooxygenase products with 20 ppm NO2 alone were blocked with the phospholipase inhibitor mepacrine and the cyclooxygenase inhibitor indomethacin. The lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) significantly reduced release of arachidonate; however, levels of thromboxane and 12-HHT were significantly increased. The results suggest a dual effect of NO2 on AM arachidonate metabolism in which low concentrations of NO2 had small effects on basal metabolism but markedly amplified the response to stimuli, while a high concentration of NO2 did the reverse. Such a complex dose response effect may have significant impact in explaining the pathologic effects of NO2. PMID- 8440202 TI - Human alveolar macrophage cytokine release in response to in vitro and in vivo asbestos exposure. AB - The lung macrophage is proposed to be involved in the development of asbestos induced pulmonary fibrosis. Knowledge of the effects of long-term asbestos exposure on lung macrophage cytokine release should better define the role of the macrophage in fibrogenesis. This study examines the effects of acute in vitro asbestos exposure and chronic in vivo asbestos exposure on human alveolar macrophage cytokine release. As indicators of asbestos-induced macrophage activation, the cellular release of IL-1 beta, TNF-alpha, IL-6, GM-CSF, and PGE2 was measured during a 24-h in vitro culture. Alveolar macrophages from normal volunteers were cultured in vitro with chrysotile asbestos. Of the factors measured, only TNF-alpha was elevated in response to asbestos exposure. Alveolar macrophages from asbestos-exposed individuals were placed into one of two groups based on their exposure history. These two groups were matched for age, smoking history, and diagnosis; none met the criteria for asbestosis. Cells isolated from subjects that had been exposed to asbestos for more than 10 years secreted enhanced basal amounts of IL-1 beta, TNF-alpha, IL-6, and PGE2, while those who had been exposed for less than 10 years did not. The results indicate that while asbestos had minimal acute effects on cytokine production by the human alveolar macrophage, intense, chronic exposure to asbestos leads to the enhanced basal release of significant amounts of several cytokines that have activity for the fibroblast, even in the absence of overt fibrosis. PMID- 8440203 TI - Mouse Clara cell 10-kDa (CC10) protein: cDNA nucleotide sequence and molecular basis for the variation in progesterone binding of CC10 from different species. AB - A protein similar to the rat Clara cell 10-kDa protein (CC10) was isolated from mouse lung homogenate by conventional chromatography. cDNA for the mouse CC10 protein was identified in the mouse lung cDNA library by using radiolabeled rat CC10 cDNA as the probe. The isolated cDNA was sequenced and the deduced primary amino acid sequence was compared to the known sequences of rabbit and hare uteroglobins and human and rat CC10 proteins. The cDNA sequence was confirmed by N-terminal amino acid sequencing of the purified protein. The purified mouse CC10 was tested for its ability to bind progesterone, and the binding was found to be 27% lower than rat CC10 and 48% lower than rabbit uteroglobin. The relative binding of mouse, rat, and human CC10 may reflect subtle structural perturbations. The only notable difference between mouse and rat CC10 is in the beta bend between helices 1 and 2, at residue 16. This difference also exists between rat and human CC10. The mouse CC10 sequence compares favorably with human CC10, which does not bind progesterone; however, the mouse CC10 does not contain M60, which has been proposed to block the binding of progesterone with human CC10. The wide variation in progesterone binding among this family of proteins casts doubt on the importance of such binding as a physiologic function. PMID- 8440204 TI - Differential influence of dexamethasone on the activity and synthesis of beta galactoside specific lectin (galaptin) during postnatal lung development. AB - This study examined the regulation of the activity and synthesis of lung beta galactoside specific lectin (galaptin) by dexamethasone (Dex). The effect of Dex was different depending on the postnatal period administered. Dex decreased galaptin activity and synthesis when administered daily during the "critical period" of alveolarization (postnatal days 3-13) described by Massaro and coworkers (J Clin Invest 76:1297-1305, 1985). The normal rise in galaptin activity (both soluble and membrane- or particulate-bound) observed for untreated controls was prevented by Dex (0.22 mg/pup day-1) treatment. Short-term (2 days) administration on days 4 and 5 had little effect. However, short-term administration of Dex at a later time (days 10-11) increased galaptin activity and synthesis. Both soluble and particulate-bound galaptin were similarly increased by Dex. These studies indicate that both pools of galaptin may be synthesized and activated by a similar mechanism. The effects of Dex on galaptin expression by the postnatal rat lung suggests that endogenous glucocorticoids play a role in the regulation of galaptin activity. The findings for rats given this level of Dex suggest that the period in which exogenous glucocorticoids are administered initially, either as short-term or chronic treatments, is important for the direction of their effect on galaptin expression. PMID- 8440205 TI - Individual differences in tolerance to shiftwork: a review. AB - Individual differences in the subjective health effects of shiftwork are reviewed. Circadian regulation and brain restitution (sleep) are the crucial mechanisms by which inter-individual factors can affect tolerance to shiftwork. On the other hand, shiftworkers can use different coping mechanisms by trying to schedule their lives and especially their sleeping habits to work at unusual hours. Individual factors related to shiftwork tolerance are discussed in two groups; first, the factors which affect primarily the circadian adjustment; and, second, the factors which mainly relate to the ability to sleep at unusual hours. The significance of circadian adjustment in shiftwork tolerance is outlined. PMID- 8440206 TI - The prediction of the adaptation of circadian rhythms to rapid time zone changes. AB - The aim of the study was to find out which factors could explain individual differences in the resynchronization speed of circadian rhythms of salivary melatonin and subjective alertness after transmeridian flights over 10 time zones. The mean age of the 40 female subjects was 33.0 +/- 6.9 years. The data were gathered by measurements of the circadian rhythms of melatonin excretion and altertness at 2 h intervals in Helsinki (Finland) two days before westward flight to Los Angeles (USA), where the measurements were repeated on the 2nd day after the flights and on the 2nd day in Finland after return flight. This shift in the acrophases of the two circadian rhythms were used as dependent variables in regression analyses. The predictors used were length of day, marital status, amount of physical exercise, age, neuroticism, extroversion, and eveningness. Age, day length, marital status, and physical exercise explained the acrophase adaptation of the melatonin rhythm after westward flight, and day length, neuroticism, and extroversion after eastward flight. Marital status, neuroticism, and physical exercise explained the variation of the acrophase adjustment of the alertness rhythm after westward flight, and age and eveningness after eastward flight. It is concluded that the amount of daylight and personality are the best predictors of the circadian rhythm adaptation after transmeridian flights. PMID- 8440207 TI - Individual differences in circadian rhythm parameters and short-term tolerance to shiftwork: a follow-up study. AB - The relationship between individual differences in the phase and amplitude of circadian rhythms and tolerance to shiftwork has been the subject of several studies. Those studies recorded circadian rhythms and shiftwork tolerance at approximately the same time. The present study aimed to examine the predictive relationships between the amplitude, phase, and mesor of 24 h rhythms obtained before exposure to shiftwork, and subsequent indices of tolerance measured after one and three years of shiftwork. The results revealed some stable relations between the various rhythm parameters and subsequent tolerance measures. Workers who had a higher mesor of positive moods, and a lower mesor of negative moods and fatigue, before entering shiftwork tended to tolerate shiftwork better. Further, those whose heart rate rhythm showed an earlier acrophase had better subsequent sleep quality scores, while those with a smaller amplitude of their temperature, negative mood and fatigue rhythms showed better night-shift tolerance. PMID- 8440208 TI - Predicting mood change on night shift. AB - This study examined the impact of night shift on six dimensions of mood. The efficacy of a range of personality, behavioural, and social/organizational predictors of these responses was also examined. Thirty-five female student nurses were studied during their first period of night work. ANOVAs indicated that only fatigue-inertia and vigour-activity were significantly affected by night work. Multivariate profile analyses revealed that significant changes were predominantly confined to the interval between the preceding rest day (B) and the first night (N1), although vigour-activity dropped significantly between N1 and N2 and rose significantly by N5 for one group of subjects. Multiple regression analyses revealed that morningness, neuroticism, work-non-work conflict, and sleep quality between shifts predicted fatigue-inertia. Extroversion and social support from both co-workers and family predicted vigour-activity. Extroversion and social support from co-workers appeared to predict the positive affect component of vigour-activity, rather than the vigour and energy component. PMID- 8440209 TI - Individual differences in night and continuously-rotating shiftwork: seeking anticipatory rather than compensatory strategy. AB - Individual differences in adaptation to night or continuously-rotating shiftwork may reflect distinct strategies of coping with temporal challenges of the environment. Rather than studying compensatory mechanisms, we have chosen the anticipatory response of the sleep onset time preceding work in order to reveal the strategy used by workers submitted to those shift systems including night work. Comprehensive interviews, taking into account several aspects of the workers' lives, allowed for a classification of the subjects in terms of adaptation to their working schedules. Night workers go to bed once a day, whereas shiftworkers prefer to allocate their sleep onsets to two different periods of the day. For both cases, the more well-adapted an individual is, according to the classification obtained by the interviews, the more regular will be the choice of sleep onset times. PMID- 8440210 TI - Burnout of female and male nurses in shiftwork. AB - Burnout and psychological stress of nurses in two- and three-shift work was analysed. The study concerned 124 mental health nurses and 162 nurses of mentally handicapped persons; half of the nurses were women. Fifty-two per cent were in three-shift work and the other half worked in two shifts. The Maslach Burnout Inventory was used as a measure of burnout. The inventory has three categories: psychological fatigue; loss of enjoyment of work; and (attitudinal) hardening. Female nurses in three-shift work reported more stress symptoms and had ceased to enjoy their work more often than women in two-shift work. Psychological fatigue and hardening were not dependent on the shift system. Male nurses experienced the same amount of burnout and stress in two- and three-shift work. Besides shiftwork, occupational demands and passive stress coping strategies contributed to the experience of burnout and stress. Family demands did not correlate with burnout of the nurses. PMID- 8440211 TI - The relationship between circadian, personality, and temperament characteristics and attitude towards shiftwork. AB - This study aimed to find out whether and to what extent circadian and personality characteristics contribute in determining attitude towards shiftwork. Two groups of female steel plant shift- (n = 54) and dayworkers (n = 54) were matched for age, job tenure, marital status, number, and age of children. The control group was made up of 2 subgroups of dayworkers with (n = 29) and without (n = 25) shiftwork experience. The subjects answered questionnaires on morningness, flexibility, languidity, neuroticism, extroversion, reactivity, and attitude towards shiftwork. Correlation analysis and multiple regression analysis were performed on the data of experimental group and control subgroups separately. Amongst current shiftworkers, the best predictors of attitude towards shiftwork were flexibility of sleeping habits and the ability to overcome drowsiness. Amongst former shiftworkers attitude was determined primarily by reactivity, but in the dayworkers without shiftwork experience no predictors of the attitude were found. The results imply that circadian and personality characteristics related to shiftwork adjustment contribute in determining attitude towards shiftwork. PMID- 8440212 TI - The design of shift systems. AB - All shift systems have advantages and drawbacks. There is no single 'optimum shift system' which can be used in industry or commerce at all work places. However, there are shift systems which are more favourable, and others which are less favourable, in the context of physiological, psychological, and social recommendations for the design of shift systems. This article discusses the following recommendations: (1) Nightwork should be reduced as much as possible. If this is not possible, quickly rotating shift systems are preferable to slowly rotating ones. Permanent nightwork does not seem to be advisable for the majority of shiftworkers. (2) Extended workdays (9-12 h) should only be contemplated, if the nature of work and the workload are suitable; the shift system is designed to minimize the accumulation of fatigue; there are adequate arrangements for cover of absentees; overtime will not be added; toxic exposure is limited; and if it is likely that a complete recovery after work and a high acceptance of the working time arrangement are possible. (3) An early start for the morning shift should be avoided. In all shiftsystems flexible working time arrangements are realizable. The highest flexibility is possible in 'time autonomous groups'. (4) Quick changeovers (e.g., from night to afternoon shift at the same day or from afternoon to morning shift) must be avoided. The number of consecutive working days should be limited to 5-7 days. Every shift system should include some free weekends with at least two successive full days off. (5) The forward rotation of shifts (phase delay, clockwise rotation) would seem to be recommendable at least in continuous shift systems. Besides the design of a shift system, implementation strategy is of particular importance for the acceptance of the shift system. PMID- 8440213 TI - Night shift dose and stress at work. AB - In a new approach to the problem of night work and its consequences, an investigation of the relationships between shift variables, stress at work (environmental and psychosocial aspects), well-being and health, and lifestyle characteristics was carried out, taking into consideration the actual number of remunerated night shifts ('night shift dose' (NSD)). Out of the entire workforce (n = 173) of a manufacturing plant of the cement industry located in Lower Austria, a group of 31 shiftworkers, working approximately 44 night shifts per year on average was examined in detail. Between night shift dose and psychosocial stress, an important relationship was detected. Taking into account workers' well being and health, the results suggest that psychosocial and environmental stress factors at work act independently from shift-related stress factors. PMID- 8440214 TI - Gender, ageing, and shiftwork intolerance. AB - The study investigated the hypothetical differences between male and female shiftworkers in their susceptibility to shiftwork-related health and social problems, with the special reference to the role of the age factor. The comparison concerned two matched-for-age-and-occupation groups of men and women, each of 83 persons, selected from the larger studied population of more than 700 workers in a Polish steel plant. The subjects were crane-operators employed in the same forward-rotated, three-shift, four-team shift system, 4:4:4 with shift changes at 06:00, 14:00, 22:00; and 48 h off following each shift block. The investigation comprised a battery of questionnaires on demographic characteristics, sleep quantity and quality, subjective health complaints, and opinions on shiftwork. The analysis of data revealed that men slept more than women, especially when working on the afternoon and night shifts. The differences became more striking and significant for all work shifts and days-off when related to declared individual sleep requirements. Women experienced more sleep disturbances than men and suffered more frequently from drowsiness during work, especially when working the morning shift. The ratings of subjective health were lower in women, with exception of respiratory complaints. Women generally suffered more than men from symptoms considered as specific to the 'intolerance syndrome', i.e. psychoneurotic, digestive, circulatory, and those of chronic fatigue. However, after passing the 'critical decade' of 40-50 years their subjective health generally improved, whereas in males one observed the consequent deterioration of health with advancing age. Women more often complained about their health and went to see the doctor, but on the other hand, they did not tend to quit shiftwork as often as did their male counterparts. PMID- 8440215 TI - The use of the Circadian Type Inventory as a measure of the circadian constructs of vigour and rigidity. AB - The Circadian Type Inventory (Folkard 1987) was administered to 191 students (150 females and 41 males). Corrected item to total correlations for both the Vigour and Rigidity scales were low to moderate. The internal reliabilities of the scales indicate that Vigour is statistically more homogeneous (0.74) than Rigidity (0.58). In the absence of the original CTI correlation matrix, replication using a 2-factor principal component varimax solution was undertaken. It explained only 26.7% of the variance. Post hoc factor analyses yielded 3 factors which explained 33.4% of the variance. The relatively low amounts of variance explained and the inadequate transfer of the circadian constructs of Rigidity and Vigour into question items does not recommend the use of the CTI to measure circadian rhythm characteristics in order to predict tolerance to shiftwork. PMID- 8440216 TI - Psychometric equivalence of an improved Basic Language Morningness (BALM) scale using industrial population within comparisons. AB - An existing 13-item composite circadian rhythm 'morningness' scale was simplified into a '(BA)sic (L)anguage (M)orningness' (BALM) scale at a seventh grade (12-13 years) reading level. It was given to 150 each of continuously rotating shifworkers and fixed-schedule dayworkers in an industrial manufacturing plant. Multiple factor analyses confirmed three prior identified factors, morningness/effort, morning alert, and evening. Morningness scores for dayworkers were higher than for shiftworkers (p < 0.001). The BALM scale revision is suitable for most worker levels. A suggested psychometrically 'purer' 9-item morningness scale omits the inconsistent evening factor scale items. PMID- 8440217 TI - Educational and intervention strategies for improving a shift system: an experience in a disabled persons' facility. AB - The improvement of an irregular three-shift system with anti-clockwise rotation of workers of a disabled persons' facility covering 42 h a week was a subject for management-labour debate. Workers were complaining of physical fatigue, high prevalence of low back pain, sleep shortages associated with short inter-shift intervals, and irregular holidays. With the co-operation of trade union members, an educational and intervention programme was designed to analyse, plan, and implement improved shift rotation schemes. The programme consisted of (a) a group study on the existing system and effects on health and working life; (b) joint planning of potential schemes; (c) communication and feedback (d) testing and evaluation; and (e) agreement on an improved system. The group study was undertaken by means of time study, questionnaire and physiological methods, and the results were jointly discussed. This led to the planning of alternative shift schemes incorporating more regular, clockwise rotation. It was agreed to stage a trial period with a view to shorter working hours. This experience indicated the importance of a stepwise intervention strategy with frequent dialogues and a participatory process focusing on the broad range of working life and health issues. PMID- 8440218 TI - The relationship between coping strategies and GHQ-scores in nurses. AB - This paper discusses the development of a situation specific questionnaire for measuring coping with shiftwork. Previously, no standardized measure appears to have been developed, even though coping behaviour is considered to be an important factor in determining tolerance to shiftwork. The results from this study indicated that the present questionnaire may have some potential. Its psychometric qualities were relatively good. Coping scores were related to psychological health, measured by GHQ-12. Analysis of variance showed a main effect of only one of the subscales (disengagement strategies) on GHQ and also a reliable interaction between disengagement and engagement on GHQ-scores. Further research into the effect of coping strategies on shiftwork tolerance is suggested. PMID- 8440219 TI - Locomotive engineers and their spouses: coffee consumption, mood, and sleep reports. AB - Locomotive engineers (train drivers) on irregular work schedules reported a general coffee consumption rate higher than that reported by a comparison sample of permanent shift factory workers. The present study examines the impact of this consumption on workday and non-workday sleep behaviour and mood ratings. Twenty seven engineers and their spouses each completed daily logs for 30 consecutive days. Daily logs were then sorted into workday and non-workday categories. Workday sleep length was significantly shorter than non-workday sleep length for both engineers and spouses. For the engineers only, coffee consumption on workdays was higher than on non-workdays. This increased coffee consumption was correlated with longer sleep latency, increased negative mood, and decreased positive mood on both work and non-workdays. This was not true for spouses. These results may be related to a days-off carry-over effect of caffeine or a general consumption behaviour characteristic. PMID- 8440221 TI - A polysomnographic study of morning and afternoon sleep quality during simulated night shift work. AB - Shiftworkers differ as to scheduling their day sleep between night shifts. An experimental study was carried out to compare the effects of morning and afternoon sleep behaviour on sleep quality within and after a period of seven night shifts. Twelve young males participated in a repeated-measures design, six sleeping in the morning and six in the afternoon after night shifts. Sleep quality was evaluated by polysomnographic and subjective measures. Morning and afternoon sleepers showed some differences in the trend of sleep changes over successive sleep periods. However, at the end of the night shift week, there were no marked differences in sleep quality. Both morning and afternoon sleep were characterized by deep sleep, and short sleep onset latencies. PMID- 8440220 TI - Nutrition and shiftwork: the use of meal classification as a new tool for qualitative/quantitative evaluation of dietary intake in shiftworkers. AB - Established nutritional science methods and a new concept for meal-classification were applied to shiftworkers (rotating 3-shift) data. The frequency of meals and snacks of different nutritional quality as a function of work schedule was evaluated, as well as the content of selected nutrients (energy, fat, sucrose, dietary fibres, ascorbic acid) in these meals and snacks. The results do not indicate that rotating 3-shift work affects the nutritional quality of the diet or the frequency of different types of meals and snacks. A qualitative classification of meals and snacks might be a cost-effective strategy for data evaluation in field studies of shift workers' eating habits when quantitative estimations of the dietary intake are to be complicated. PMID- 8440222 TI - A comparison of circadian rhythms in work performance between physically active and inactive subjects. AB - This study compared circadian rhythms in physiological, subjective, and performance measures between groups exhibiting different levels of habitual physical activity. Fourteen male subjects, aged 19-29 years, were assigned to a physically active (group I, n = 7) or a physically inactive (group II, n = 7) group on the basis of leisure-time physical activity. Rectal temperature, oral temperature, resting pulse rate, subjective arousal and sleepiness were measured at 02:00, 06:00, 10:00, 14:00, 18:00 and 22:00 in a counter-balanced sequence for each subject. Whole-body flexibility, back and leg strength, grip strength (right and left), flight time in a vertical jump, PWC150, and self-chosen work-rate were also recorded at each time point. At least 8h separated each test session. Subjects avoided exercise 48h prior to, and during the experiment. Data were subjected to the group cosinor method. Group I evidenced 1.5-2.5 times greater rhythm amplitudes than Group II for oral temperature, subjective arousal, sleepiness, flexibility, left and right grip strength, submaximal heart rate, and self-chosen work-rate (p < 0.05). Oral temperature and arousal for Group I were lower than Group II only at 06:00. Early morning troughs in most of the performance measures were significantly greater for Group I (p < 0.05). The groups did not differ with respect to phasing of the rhythms (p < 0.05). These results confirm with physical performance measures that rhythm amplitudes are higher for physically fit subjects. This could be attributed to greater early morning troughs in the measures for active individuals. Since the subjects were sedentary immediately prior to testing, it is plausible that these findings are training effects of physical activity. PMID- 8440223 TI - Dissecting circadian performance rhythms: implications for shiftwork. AB - Safety on shift systems will depend, at least in part, on the adjustment of shiftworkers' circadian (c.24h) rhythms in performance capabilities which will in turn depend on their underlying control. In the present study three volunteers lived on a 30h 'day' and performed a range of tasks every 2h (while awake) to allow estimates of the relative magnitude of the endogenous (body clock) and exogenous (masking) components of their rhythms to be made. Performance rhythms were found to differ considerably in this respect with, for example, speed on a 4 choice serial reaction time task appearing to be largely endogenously determined while that on a 5-target Sternberg task was more dependent on exogenous (i.e., 30h) factors. This implies that performance measures may adjust at very different rates to one another to night work, and hence that the optimal form of shift system may vary according to the precise demands of the shiftworker's task. PMID- 8440224 TI - Adaptation to permanent night work: the number of consecutive work nights and motivated choice. AB - To study the effects of different patterns of days on and days off duty within a permanent night shift schedule, we studied two groups of female permanent night nurses, one (n = 42) working 'many' nights in a row, and the other (n = 36) working 'few' nights in a row. The groups were matched for several important moderating variables. All nurses were interviewed individually, and they answered several questionnaires. A MANOVA revealed no statistically significant differences in subjective health between the two groups. Nor was any difference found for satisfaction measures. The many-night group however seemed to put more effort into dealing with their schedule; they used more active coping, had a higher cigarette consumption, and engaged more in sport. They also stayed one hour less in bed during the day after the last night shift. It is concluded that neither schedule was a clear threat to subjective health because the acceptance of permanent night work was the result of a motivated choice and because social support was high. The differences between the two schedules were not large enough to suggest that one of them should be favoured over the other. PMID- 8440225 TI - The perceptions and feelings of shiftworkers' partners. AB - The views and feelings of shiftworkers' partners are rarely sought in shiftwork research. For this study, the partners of UK nuclear power shiftworkers were surveyed in relation to how their spouse's shiftwork affected them personally. A sizeable proportion of partners reported being unhappy with their spouse's shiftwork and that their lives were disrupted quite substantially by it. Partners were also asked for their perceptions of the shiftworkers' shift-related problems. Importantly, it would appear that shiftwork had a significant negative impact upon the lives of the partners. In view of these results and the relative paucity of research in this area, future investigation of the effects of unusual work hours upon shiftworkers' partners and families is warranted. PMID- 8440226 TI - Trends in approaches to night and shiftwork and new international standards. AB - While relatively few countries have changed their working time legislation in recent years, new working time patterns show some changes in approaches to night and shiftwork. Prominent trends include (i) the spread of irregular hours of work to different sectors, including services, often as a result of decoupling business hours from individual working hours; (ii) greater flexibility, often in return for shorter hours, in covering operating hours by different individuals; (iii) the appearance of complex combinations of different categories of working time arrangements, such as a combination of full-time semi-continuous shifts and part-time weekend shifts; and (iv) the adoption of a complex process for changes in schemes, incorporating group study and joint planning. Importantly, these trends reflect fundamental changes in the concept of night work (and that of nightworkers). The issues related to these recent trends were apparent in the two year debate that led to new international labour standards, the Night Work Convention (No. 171) and Recommendation (No. 178), 1990, both of which apply to both sexes and to nearly all occupations. Also adopted was the Protocol of 1990 to the Night Work (Women) Convention (No. 89) of 1948, under which national laws or regulations may now permit night work of women in industry under strictly defined conditions. The new Convention and Recommendation define 'nightworker' to include workers performing a substantial amount of night work. They prescribe a variety of actions to improve the quality of working life of such workers, including measures related to working hours, rest periods, safety and health, transfer to day work, maternity protection, social services, and consultations. Strategies should be adopted that take into account the local situation, that are participatory, and that take due account of the diverse aspects of working life associated with the new concept of night work. PMID- 8440227 TI - Have we underestimated shiftworkers' problems? Evidence from a 'reminiscence' study. AB - This paper argues that shiftworkers may have gradually habituated to their problems and hence that they underestimate them. Some support for this view was obtained in a 'reminiscence' questionnaire study of retired UK Police Officers who had all subsequently taken on another (mainly day-time) job. They completed a specially constructed questionnaire, which included several measures of health and well being, and in which they were asked to reminisce about how they had felt while still a shiftworker. These reminiscence scores were compared to their current perception of how they were. The results clearly indicated that individuals in retrospect perceive their situation as being worse than they realised at the time. This effect was most marked for scores on the General Health Questionnaire and Chronic Fatigue scale. The results of this study draw attention to a potential confounding in much of the shiftwork literature which demands further, more detailed, investigation. PMID- 8440228 TI - The after-effects of night work on short-term memory performance. AB - The aim of this study was to assess the after-effects of night work on mental performance. Twenty experienced shift workers were examined in a baseline condition and during recovery after a night shift period. For control purposes eight other workers were studied in a similar baseline condition and during recovery after a non-night shift period. The subjects performed memory search tasks before and after a bicycle ergometer test. Cycling had different effects on mental performance, leaving the speed and accuracy of the reactions unchanged in the baseline and the non-night-recovery condition, while decreasing the mental performance in the night-recovery condition. Also in this condition a higher level mental effort investment was measured. These results suggest an incomplete recovery on the first fully undisturbed day-off (32 h) after a period of night work, manifesting itself in a deterioration of the efficiency of the information processing. PMID- 8440229 TI - Day- and shiftworkers' leisure time. AB - Cross-sectional studies of working and living conditions were conducted in two Brazilian petrochemical plants between 1988-1989. This paper presents analyses of reported activities undertaken during day- and shiftworkers' leisure time. One hundred and sixteen workers (67 continuous shiftworkers) daily logged standard protocols of all leisure activities, for three consecutive weeks. Workers logged 11,957 instances grouped in 27 different activities. The 14 most commonly mentioned leisure activities were analysed. Those most reported were meals with the family (breakfast, lunch, and dinner) and home TV viewing. Using chi 2 statistics, the results showed that the two factors studied--activities and work schedules (day and shift)--were not related. Analysing estimated coefficients of a second order log linear model, only a very few of the 14 activities most mentioned, did not differ in their frequencies between day and shiftworkers of the same plant. The same happened with the 12 activities most-mentioned of both plants: shiftworkers and dayworkers showed significant differences (p < 0.0001) on almost all frequencies of those activities mentioned. Hypotheses are made to explain some of the results. Home placement, and types of shiftwork schedules (weekly or swiftly rotating shifts) can be responsible for some of the activities performed during the workers' leisure time. Further investigation of those activities which are disturbed or cannot be performed due to work schedules is suggested. PMID- 8440230 TI - Advancing versus delaying shift systems. AB - Two hundred and sixty-one shiftworkers from a range of UK industrial and service organizations, took part in a study to determine the impact of the direction of shift rotation on the health and well-being of the individuals concerned. All the systems were continuous, rotating over three shifts. Systems were classified according to whether they delayed (i.e., rotated in a forward direction) or advanced (i.e., rotated in a backward direction). In addition, advancing systems were divided into those which incorporated a quick return (i.e., a break of only 8 h when changing from one shift to another) and those which did not. The results add some support for the use of delaying as opposed to advancing systems, and highlight the detrimental effects of incorporating a quick return into an advancing system. PMID- 8440231 TI - Does the 'forbidden zone' for sleep onset influence morning shift sleep duration? AB - Shiftwork researchers have concentrated on the problems on the night shift, and have tended to neglect the truncation of sleep that can occur before morning, or 'early', shifts. We examined the sleep timing and duration between morning shifts of shiftworkers on a variety of shift systems. The extent of morning shift sleep truncation depended very largely on the time at which individuals had to leave home. Further, there was some suggestive evidence that the failure of individuals to compensate by going to sleep earlier was not simply due to social pressures to stay up. Rather it would appear to have depended, at least in part, on the biological clock determined 'forbidden zone' for sleep that occurs shortly before habitual sleep onset. PMID- 8440232 TI - Extreme resistance to potato virus X infection in plants expressing a modified component of the putative viral replicase. AB - Three types of mutation were introduced into the sequence encoding the GDD motif of the putative replicase component of potato virus X (PVX). All three mutations rendered the viral genome completely noninfectious when inoculated into Nicotiana clevelandii or into protoplasts of Nicotiana tabacum (cv. Samsun NN). In order to test whether these negative mutations could inactivate the viral genome in trans, the mutant genes were expressed in transformed N.tabacum (cv. Samsun NN) under control of the 35S RNA promoter of cauliflower mosaic virus and the transformed lines were inoculated with PVX. In 10 lines tested in which the GDD motif was expressed as GAD or GED there was no effect on susceptibility to PVX. In two of four lines transformed to express the ADD form of the conserved motif, the F1 and F2 progeny plants were highly resistant to infection by PVX, although only to strains closely related to the source of the transgene. The resistance was associated with suppression of PVX accumulation in the inoculated and systemic leaves and in protoplasts of the transformed plants, although some low level viral RNA production was observed in the inoculated but not the systemic leaves when the inoculum was as high as 100 or 250 micrograms/ml PVX RNA. These results suggest for a plant virus, as reported previously for Q beta phage, that virus resistance may be engineered by expression of dominant negative mutant forms of viral genes in transformed cells. PMID- 8440233 TI - 8-Methoxypsoralen induced mutations are highly targeted at crosslinkable sites of photoaddition on the non-transcribed strand of a mammalian chromosomal gene. AB - We have determined the mutational specificity of 8-methoxypsoralen photoaddition at the endogenous adenine phosphoribosyltransferase gene of Chinese hamster ovary cells hemizygous for this locus. In addition, the distribution of 8 methoxypsoralen photo-adducts was resolved in vitro at the DNA sequence level, and compared with the observed site specificity for mutation. Among 27 mutants characterized, all were single base changes at AT base pairs: 16 A:T-->T:A, six A:T-->C:G, four A:T-->G:C and one -T frameshift. All these vents were targeted to potential sites of photoaddition. The vast majority of these sites were also detectable in vitro, suggesting that 8-methoxypsoralen plus UVA-induced mutational hotspots may be damage hotspots. Furthermore 26/27 mutations occurred at crosslinkable 5'TpA sites, supporting the notion that 8-methoxypsoralen biadducts rather than monoadducts are major premutagenic lesions in mammalian cells. Since 90% of our mutation collection could have resulted from damage on the non-transcribed strand, it appears that photoadducted thymine residues on the transcribed strand of the adenine phosphoribosyltransferase gene may be preferentially repaired. We therefore suggest a model for mutagenesis, induced by psoralen biadducts, based on the preferential incision of biadducts followed by translesion synthesis past modified T bases persisting on the non-transcribed strand. PMID- 8440234 TI - Construction and characterization of a mercury-independent MerR activator (MerRAC): transcriptional activation in the absence of Hg(II) is accompanied by DNA distortion. AB - The MeR regulatory protein of transposon Tn501 controls the expression of the mercury resistance (mer) genes in response to the concentration of mercuric ions. MerR is unique among prokaryotic regulatory proteins so far described in that it acts as a repressor [-Hg(II)] and an activator [+Hg(II)] of transcription of the mer genes, but binds to a single site on the DNA in both cases. This transcriptional activation process has been postulated to involve a protein induced conformational change in the DNA that allows RNA polymerase more readily to form an open complex at the promoter. It has been shown [Frantz and O'Halloran (1990) Biochemistry, 29, 4747-4751] that activation of transcription by MerR in the presence of mercury is accompanied by hypersensitivity of the operator to chemical nucleases that are sensitive to local distortion in DNA structure. Here we describe specific mutations in MerR that allow the protein to stimulate transcription in the absence of the allosteric activator Hg(II). We demonstrate that the degree of activation caused by these mutants directly correlates with the degree of DNA distortion as measured by the hypersensitivity of MerR-DNA complexes to the nuclease Cu-5-phenyl-o-phenanthroline. These results support the model described above. PMID- 8440235 TI - A nucleosome-dependent static loop potentiates estrogen-regulated transcription from the Xenopus vitellogenin B1 promoter in vitro. AB - We describe the transcriptional potentiation in estrogen responsive transcription extracts of the Xenopus vitellogenin B1 gene promoter through the formation of a positioned nucleosome. Nuclease digestion and hydroxyl radical cleavage indicate that strong, DNA sequence-directed positioning of a nucleosome occurs between 300 and -140 relative to the start site of transcription. Deletion of this DNA sequence abolishes the potentiation of transcription due to nucleosome assembly. The wrapping of DNA around the histone core of the nucleosome positioned between 300 and -140 creates a static loop in which distal estrogen receptor binding sites are brought close to proximal promoter elements. This might facilitate interactions between the trans-acting factors themselves and/or RNA polymerase. Such a nucleosome provides an example of how chromatin structure might have a positive effect on the transcription process. PMID- 8440236 TI - Interferon-beta promoters contain a DNA element that acts as a position independent silencer on the NF-kappa B site. AB - The human interferon-beta (IFN-beta) promoter contains several functional domains that contribute to its virus-inducible regulation. One of them, PRDII, and NF kappa B-binding sequence, can function as a constitutively activating element. Due to the presence of a negative regulatory domain that mediates a constitutive repression the natural IFN-beta promoter is silent in the non-induced state. Within this domain we have delimited an 11 bp element that acts as a negative regulatory element (NRE) of PRDII. Although the NRE is physically overlapping with PRDII in the IFN-beta promoter, it acts as a position-independent silencer of PRDII. Virus infection, which leads to the transcriptional activation of the IFN-beta promoter, does not alter the negative activity of the NRE on an isolated PRDII. It is the cooperative effect of PRDI and PRDII that is able to overcome the NRE function after virus infection. By UV cross-linking analysis using uninduced and virus-induced nuclear extracts, we show that two factors with molecular masses of approximately 95 and 100 kDa bind to the NRE. PMID- 8440237 TI - mdm2 expression is induced by wild type p53 activity. AB - We have recently characterized a 95 kDa protein, p95, which exhibits enhanced binding to temperature-sensitive p53 (ts-p53) when cells are shifted down to 32.5 degrees C, a temperature at which ts-p53 possesses wild-type (wt)-like activities. In the present study we show that p95 is a product of the mdm2 putative proto-oncogene. The enhanced complex formation of mdm2 with ts-p53 in cells maintained at 32.5 degrees C is due to an elevation in total mdm2 protein levels following the temperature shift. We further demonstrate that the induction of mdm2 expression by t p53 activity is at the mRNA level. The induction occurs with very rapid kinetics and does not require de novo protein synthesis, suggesting a direct involvement of p53 in the process. Based on these data and on recent findings implicating p53 as a transcription factor, we suggest that the mdm2 gene is a target for activation by wt p53. In view of the ability of mdm2 to act as a specific antagonist of p53 activity, this induction process may serve to tightly autoregulate p53 activity in living cells. PMID- 8440238 TI - A region in the C-terminus of adenovirus 2/5 E1a protein is required for association with a cellular phosphoprotein and important for the negative modulation of T24-ras mediated transformation, tumorigenesis and metastasis. AB - We have examined a series of small deletion mutants within exon 2 of the adenovirus 2/5 E1A oncogene product, the 243R protein, for immortalization, ras cooperative transformation, tumorigenesis and metastasis. Compared with wild-type 243R, various deletion mutants located between residues 193 and 243 cooperated more efficiently with ras to induce large transformed foci of less adherent cells that were tumorigenic and metastatic. However, the greatest enhancement of transformation (comparable to that obtained with a deletion of the C-terminal 67 amino acids) was observed with a mutant carrying a deletion of residues 225-238. This mutant was also more defective in immortalization. These results suggest that this 14 amino acid region may contain a function that is important for immortalization and negative modulation of tumorigenesis and metastasis. To identify cellular proteins that may associate with the exon 2-coded region of E1A (C-terminal half) and modulate its transformation potential, we constructed a chimeric gene coding for the C-terminal 68 amino acids of E1a fused to bacterial glutathione-S-transferase (GST). This fusion protein was used to purify cellular proteins that bind to the C-terminal region of E1a. A 48 kDa cellular protein doublet (designated CtBP) was found to bind specifically to the GST-E1a C terminal fusion protein as well as to bacterially expressed full-length E1a (243R) protein. It also co-immunoprecipitated specifically with E1a. Analysis of a panel of GST-E1a C-terminal mutant proteins indicates that residues 225-238 are required for the association of E1a and CtBP, suggesting a correlation between the association of CtBP and the immortalization and transformation modulating activities of exon 2. CtBP is a phosphoprotein and the level of phosphorylation of CtBP appears to be regulated during the cell cycle, suggesting that it may play an important role during cellular proliferation. PMID- 8440239 TI - Distinct TFIID complexes mediate the effect of different transcriptional activators. AB - Multiple chromatographically separable complexes containing the TATA binding protein (TBP), which exhibit different functional properties, exist in HeLa cells. At least three distinct subpopulations of such complexes can be functionally defined as TFIID since they function with RNA polymerase II. Using a partially reconstituted HeLa cell in vitro transcription system and immunoprecipitation with a monoclonal antibody directed against TBP, we show that stimulation of transcription by the chimeric activators GAL-VP16, GAL-TEF-1 and GAL-ER(EF) requires the presence of factors which are tightly associated with these TFIID complexes. Moreover, the activity of GAL-TEF-1 appears to be mediated by at least two chromatographically distinct populations of TFIID. The factor(s) associated with one of these populations is also required for the activity of GAL ER (EF) and GAL-VP16, while the factor(s) associated with the other population functions selectively with GAL-TEF-1. These two TFIID populations are composed of both common and unique TBP associated factors (TAFs). PMID- 8440240 TI - Human transcription factor USF stimulates transcription through the initiator elements of the HIV-1 and the Ad-ML promoters. AB - Earlier in vitro studies identified USF as a cellular factor which activates the adenovirus major late (Ad-ML) promoter by binding to an E-box motif located at position -60 with respect to the cap site. Purified USF contains 44 and 43 kDa polypeptides, and the latter was found (by cDNA cloning) to be a helix-loop-helix protein. In this report, we demonstrate a 25-to 30-fold stimulation of transcription via an upstream binding site by ectopic expression of the 43 kDa form of USF (USF43) in transient transfection assays. More recent data have also revealed alternate interactions of USF43 at pyrimidine-rich (consensus YYAYTCYY) initiator (Inr) elements present in a variety of core promoters. In agreement with this observation, we show here that USF43 can recognize the initiator elements of the HIV-1 promoter, as well as those in the Ad-ML promoter, and that ectopic expression of USF43 can stimulate markedly the corresponding core promoters (TATA and initiator elements) when analyzed in transient co transfection assays. Mutations in either Inr 1 or Inr 2 reduced the USF43 dependent transcription activity in vivo. In addition, in vitro transcription assays showed that mutations in either or both of the Inr 1 and Inr 2 sequences of the HIV-1 and Ad-ML promoters could affect transcription efficiency, but not the position of the transcriptional start site. These results indicate that USF43 can stimulate transcription through initiator elements in two viral promoters, although the exact mechanism and physiological significance of this effect remain unclear. PMID- 8440241 TI - Recognition of the Xenopus ribosomal core promoter by the transcription factor xUBF involves multiple HMG box domains and leads to an xUBF interdomain interaction. AB - The interaction of the ribosomal transcription factor xUBF with the RNA polymerase I core promoter of Xenopus laevis has been studied both at the DNA and protein levels. It is shown that a single xUBF-DNA complex forms over the 40S initiation site (+1) and involves at least the DNA sequences between -20 and +60 bp. DNA sequences upstream of +10 and downstream of +18 are each sufficient to direct complex formation independently. HMG box 1 of xUBF independently recognizes the sequences -20 to -1 and +1 to +22 and the addition of the N terminal dimerization domain to HMG box 1 stabilizes its interaction with these sequences approximately 10-fold. HMG boxes 2/3 interact with the DNA downstream of +22 and can independently position xUBF across the initiation site. The C terminal segment of xUBF, HMG boxes 4, 5 or the acidic domain, directly or indirectly interact with HMG box 1, making the core promoter sequences between 11 and -15 hypersensitive to DNase. This interaction also requires the DNA sequences between +17 and +32, i.e. the HMG box 2/3 binding site. The data suggest extensive folding of the core promoter within the xUBF complex. PMID- 8440242 TI - The Drosophila doublesex proteins share a novel zinc finger related DNA binding domain. AB - The doublesex gene of Drosophila melanogaster is the final member of a well characterized hierarchy of genes that controls somatic sex determination and differentiation. The male-specific and female-specific doublesex polypeptides occupy a terminal position in the hierarchy, and thus regulate those genes responsible for the development of sexually dimorphic characteristics of the fly. To investigate the molecular mechanism by which these two related proteins interact with specific target genes, we have identified and characterized their DNA binding domains. Using gel mobility shift experiments with sequentially deleted polypeptides, site-directed mutagenesis and spectrophotometric assays, we have shown that the two doublesex proteins share a common and novel zinc finger related DNA binding domain distinct from any reported class of zinc binding proteins. We have further shown that of 10 null dsx alleles, six encode proteins deficient in DNA binding activity, and that three of these alleles are the result of mutations that alter cysteine and histidine residues in the metal binding domain. Our results provide evidence that both the male-specific and female specific doublesex proteins share and depend upon the same DNA binding domain for function in vivo, suggesting that both proteins bind to, but differentially regulate, a common set of genes in both sexes. PMID- 8440243 TI - The expression pattern of a Drosophila homolog to the mouse transcription factor HNF-4 suggests a determinative role in gut formation. AB - A Drosophila gene, HNF-4(D), was selected by cross-hybridization with a probe to rat HNF-4 (hepatocyte nuclear factor 4), a steroid hormone receptor super-family member that plays an important role in liver-specific gene expression. The Drosophila gene matched the mouse gene in 60 out of 66 amino acids in the zinc finger DNA binding domain and in 140 out of 206 amino acids in the domain that specifies dimerization and ligand binding. HNF-4(D) is expressed in developing Drosophila embryos in mid-gut, fat bodies and malpighian tubules, a striking similarity to its limited expression in the adult intestine, liver and kidney of the mouse. Furthermore, Drosophila mutant that has a chromosome deletion spanning the HNF-4(D) locus fails to develop tissues where HNF-4(D) is expressed during late embryogenesis. These findings together with the earlier realization that the rat hepatocyte nuclear factor 3 (HNF-3) and forkhead, a Drosophila gene required for anterior and posterior gut formation, had virtually the identical DNA binding domain, lead us to speculate that a group of genes that participate in gut formation of invertebrates has survived in evolution to perform similar functions in mammals. PMID- 8440244 TI - In vivo footprinting of a low molecular weight glutenin gene (LMWG-1D1) in wheat endosperm. AB - The quality of the wheat grain is determined by the quantity and composition of storage proteins (prolamins) which are synthesized exclusively in endosperm tissue. We are investigating the mechanisms underlying the regulation of expression of a prolamin gene, the low molecular weight glutenin gene LMWG-1D1. The LMWG-1D1 promoter contains the endosperm box, a sequence motif highly conserved in the promoter region of a large number of storage protein genes, which is thought to confer endosperm-specific expression of prolamin genes. Here we show by in vivo DMS footprinting of wheat endosperm tissue that the endosperm box becomes occupied by putative trans-acting factors during grain ripening. During early stages of development the endosperm motif within the 5' half of the endosperm box becomes occupied first, followed by binding of a second activity to a GCN4/jun-like motif in the 3' half just prior to the stage of maximum gene expression. Occupancy of the endosperm box is highly tissue-specific: no protection was observed in husk and leaf tissues. Several binding activities were identified in vitro from nuclear protein extracts of wheat endosperm which bind specifically to the endosperm and GCN4/jun motifs identified by in vivo footprinting. PMID- 8440245 TI - Detection and characterization of a plastid envelope DNA-binding protein which may anchor plastid nucleoids. AB - Chloroplast DNA (cpDNA) binds to the envelope membrane of actively dividing chloroplasts (plastids) in young pea leaves. South-western blotting was used to identify and characterize the protein involved in the binding of cpDNA to the envelope membrane. A 130 kDa protein in the inner chloroplast (plastid) envelope membrane binds specific sequences within the cpDNA. These included a 0.41 kbp sequence located upstream of the psaAB gene, a 0.57 kbp sequence located downstream of the petA gene and a 1.2 kbp sequence located within the rpoC2 gene. The protein was detected in the envelope membrane of young pea leaves in which the cpDNA had been located by fluorescence microscopy at the chloroplast periphery, whereas it was undetectable in mature leaves. We therefore propose that the 130 kDa protein is involved in the binding of cpDNA to the envelope membrane, and named it plastid envelope DNA-binding protein. PMID- 8440246 TI - Chloroplast rps15 and the rpoB/C1/C2 gene cluster are strongly transcribed in ribosome-deficient plastids: evidence for a functioning non-chloroplast-encoded RNA polymerase. AB - Transcription of plastid genes and transcript accumulation were investigated in white leaves of the albostrians mutant of barley (Hordeum vulgare) and in heat bleached leaves of rye (Secale cereale) as well as in normal green leaves of both species. Cells of white leaves of the mutant and cells of heat-bleached leaves bear undifferentiated plastids lacking ribosomes and, consequently, plastid translation products, among them the subunits of a putative chloroplast RNA polymerase encoded by the plastid genes rpoA, B, C1 and C2. The following results were obtained. (i) Plastid genes are transcribed despite the lack of chloroplast gene-encoded RNA polymerase subunits. The plastid origin of these transcripts was proven. This finding provides evidence for the existence of a plastid RNA polymerase encoded entirely by nuclear genes. (ii) Transcripts of the rpo genes and of rps15, but not of genes involved in photosynthesis and related processes (psbA, rbcL, atpI-H), were abundantly accumulated in ribosome-deficient plastids. In contrast, chloroplasts accumulated transcripts of photosynthetic, but not of the rpo genes. (iii) Differences in transcript accumulation between chloroplasts and ribosome-deficient plastids are due to different relative transcription rates and different transcript stability. (iv) The observed differences in transcription are not caused by an altered pattern of methylation of plastid DNA. Thus, the prokaryotic plastid genome of higher plants is transcribed by two RNA polymerases. The observed differences in transcription between chloroplasts and undifferentiated plastids might reflect different functions of the two enzymes. PMID- 8440247 TI - Assembly of a processive messenger RNA polyadenylation complex. AB - Polyadenylation of mRNA precursors by poly(A) polymerase depends on two specificity factors and their recognition sequences. These are cleavage and polyadenylation specificity factor (CPSF), recognizing the polyadenylation signal AAUAAA, and poly(A) binding protein II (PAB II), interacting with the growing poly(A) tail. Their effects are independent of ATP and an RNA 5'-cap. Analysis of RNA-protein interactions by non-denaturing gel electrophoresis shows that CPSF, PAB II and poly(A) polymerase form a quaternary complex with the substrate RNA that transiently stabilizes the binding of poly(A) polymerase to the RNA 3'-end. Only the complex formed from all three proteins is competent for the processive synthesis of a full-length poly(A) tail. PMID- 8440248 TI - The RNA binding site of bacteriophage MS2 coat protein. AB - The coat protein of the RNA bacteriophage MS2 binds a specific stem-loop structure in viral RNA to accomplish encapsidation of the genome and translational repression of replicase synthesis. In order to identify the structural components of coat protein required for its RNA binding function, a series of repressor-defective mutants has been isolated. To ensure that the repressor defects were due to substitution of binding site residues, the mutant coat proteins were screened for retention of the ability to form virus-like particles. Since virus assembly presumably requires native structure, this approach eliminated mutants whose repressor defects were secondary consequences of protein folding or stability defects. Each of the variant coat proteins was purified and its ability to bind operator RNA in vitro was measured. DNA sequence analysis identified the nucleotide and amino acid substitutions responsible for reduced RNA binding affinity. Localization of the substituted sites in the three dimensional structure of coat protein reveals that amino acid residues on three adjacent strands of the coat protein beta-sheet are required for translational repression and RNA binding. The sidechains of the affected residues form a contiguous patch on the interior surface of the viral coat. PMID- 8440249 TI - Accumulation of D1 polypeptide in tobacco plastids is regulated via the untranslated region of the psbA mRNA. AB - The plastid psbA mRNA is present in all tissues, while the encoded 32 kDa D1 protein of photosystem II accumulates tissue-specifically and in response to light. To study the regulation of D1 accumulation, a chimeric uidA gene encoding beta-glucuronidase (GUS) under control of the psbA 5'- and 3'-regulatory regions (224 and 393 bp, respectively), was integrated into the tobacco plastid genome. A high level of GUS accumulation in leaves and the lack of GUS in roots, with uidA mRNA present in both tissues, indicated tissue-specific accumulation of the chimeric gene product. Light-regulated accumulation of GUS in seedlings was shown. (i) Light-induced accumulation (100-fold) of GUS in etiolated cotyledons was accompanied by only a modest increase in mRNA levels. (ii) Inhibition of GUS synthesis was observed in cotyledons when light-grown seedlings were transferred to the dark, with no reduction in mRNA levels. Tissue-specific and light regulated accumulation of GUS indicates that D1 accumulation is controlled via cis-acting regulatory elements in the untranslated region of the psbA mRNA. We propose that in tobacco, control of translation initiation is the primary mechanism regulating D1 protein accumulation. PMID- 8440250 TI - Non-standard translational events in Candida albicans mediated by an unusual seryl-tRNA with a 5'-CAG-3' (leucine) anticodon. AB - From in vitro translation studies we have previously demonstrated the existence of an apparent efficient UAG (amber) suppressor tRNA in the dimorphic fungus Candida albicans (Santos et al., 1990). Using an in vitro assay for termination codon readthrough the tRNA responsible was purified to homogeneity from C.albicans cells. The determined sequence of the purified tRNA predicts a 5'-CAG 3' anticodon that should decode the leucine codon CUG and not the UAG termination codon as originally hypothesized. However, the tRNA(CAG) sequence shows greater nucleotide homology with seryl-tRNAs from the closely related yeast Saccharomyces cerevisiae than with leucyl-tRNAs from the same species. In vitro tRNA-charging studies demonstrated that the purified tRNA(CAG) is charged with Ser. The gene encoding the tRNA was cloned from C.albicans by a PCR-based strategy and DNA sequence analysis confirmed both the structure of the tRNA(CAG) and the absence of any introns in the tRNA gene. The copy number of the tRNA(CAG) gene (1-2 genes per haploid genome) is in agreement with the relatively low abundance (< 0.5% total tRNA) of this tRNA. In vitro translation studies revealed that the purified tRNA(CAG) could induce apparent translational bypass of all three termination codons. However, peptide mapping of in vitro translation products demonstrated that the tRNA(CAG) induces translational misreading in the amino-terminal region of two RNA templates employed, namely the rabbit alpha- and beta-globin mRNAs. These results suggest that the C.albicans tRNA(CAG) is not an 'omnipotent' suppressor tRNA but rather may mediate a novel non-standard translational event in vitro during the translation of the CUG codon. The possible nature of this non standard translation event is discussed in the context of both the unusual structural features of the tRNA(CAG) and its in vitro behaviour. PMID- 8440251 TI - Topography of the E site on the Escherichia coli ribosome. AB - Three photoreactive tRNA probes have been utilized in order to identify ribosomal components that are in contact with the aminoacyl acceptor end and the anticodon loop of tRNA bound to the E site of Escherichia coli ribosomes. Two of the probes were derivatives of E. coli tRNA(Phe) in which adenosines at positions 73 and 76 were replaced by 2-azidoadenosine. The third probe was derived from yeast tRNA(Phe) by substituting wyosine at position 37 with 2-azidoadenosine. Despite the modifications, all of the photoreactive tRNA species were able to bind to the E site of E. coli ribosomes programmed with poly(A) and, upon irradiation, formed covalent adducts with the ribosomal subunits. The tRNA(Phe) probes modified at or near the 3' terminus exclusively labeled protein L33 in the 50S subunit. The tRNA(Phe) derivative containing 2-azidoadenosine within the anticodon loop became cross-linked to protein S11 as well as to a segment of the 16S rRNA encompassing the 3'-terminal 30 nucleotides. We have located the two extremities of the E site bound tRNA on the ribosomal subunits according to the positions of L33, S11 and the 3' end of 16S rRNA defined by immune electron microscopy. Our results demonstrate conclusively that the E site is topographically distinct from either the P site or the A site, and that it is located alongside the P site as expected for the tRNA exit site. PMID- 8440252 TI - Regulation of the Escherichia coli rmf gene encoding the ribosome modulation factor: growth phase- and growth rate-dependent control. AB - Ribosome modulation factor (RMF) is a protein specifically associated with 100S ribosome dimers which start to accumulate in Escherichia coli cells upon growth transition from exponential to stationary phase. The structural gene, rmf, encoding the 55 amino acid residues RMF protein has been cloned from the 21.8 min region of the E. coli genome and sequenced. While rmf was silent in rapidly growing exponential phase cells, a high level of transcription took place concomitantly with the growth transition to stationary phase. Under slow growth conditions, rmf was expressed even in exponential phase and there was an inverse relationship between the expression of rmf and the cell growth rate. Thus, the expression profile of rmf is contrary to those of genes for ribosomal components and ribosome-associated proteins constituting the translational apparatus. The katF gene product, a stationary phase-specific sigma factor, was not required for the expression of rmf. Disruption of rmf resulted in loss of ribosome dimers and reduction of cell viability during stationary phase. PMID- 8440253 TI - Genes for a beta-lactamase, a penicillin-binding protein and a transmembrane protein are clustered with the cephamycin biosynthetic genes in Nocardia lactamdurans. AB - Three genes encoding a typical beta-lactamase, a penicillin-binding protein (PBP4) and a transmembrane protein are located in the cluster of cephamycin biosynthetic genes in Nocardia lactamdurans. The similarity of the N. lactamdurans beta-lactamase to class A beta-lactamases from clinical isolates supports the hypothesis that antibiotic resistance genes in pathogenic bacteria are derived from antibiotic-producing organisms. The beta-lactamase is secreted and is active against penicillins (including the biosynthetic intermediates penicillin N and isopenicillin N), but not against cephamycin C. The beta lactamase is synthesized during the active growth phase, prior to the formation of three cephamycin biosynthetic enzymes. The PBP of N. lactamdurans is a low M(r) protein that is very similar to DD-carboxypeptidases of Streptomyces and Actinomadura. The pbp gene product expressed in Streptomyces lividans accumulates in the membrane fraction. By disruption of N. lactamdurans protoplasts, the PBP4 was shown to be located in the plasma membrane. Eight PBPs were found in the membranes of N. lactamdurans, none of which bind cephamycin C, which explains the resistance of this strain to its own antibiotic. A transmembrane protein encoded by the cmcT gene of the cluster also accumulates in the membrane fraction and is probably related to the control of synthesis and secretion of the antibiotic. A balanced synthesis of beta-lactam antibiotics, beta-lactamase and PBP is postulated to be critical for the survival of beta-lactam-producing actinomycetes. PMID- 8440254 TI - Variable opacity (Opa) outer membrane proteins account for the cell tropisms displayed by Neisseria gonorrhoeae for human leukocytes and epithelial cells. AB - Opacity proteins (Opa) of Neisseria gonorrhoeae, a family of variant outer membrane proteins implicated in pathogenesis, are subject to phase variation. In strain MS11, 11 different opa gene alleles have been identified, the expression of which can be turned on and off independently. Using a reverse genetic approach, we demonstrate that a single Opa protein variant of strain MS11, Opa50, enables gonococci to invade epithelial cells. The remaining variant Opa proteins show no, or very little, specificity for epithelial cells but instead confer interaction with human polymorphonuclear neutrophils (PMNs). Thus, depending on the opa allele expressed, gonococci are capable of invading epithelial cells or of interacting with human leukocytes. The respective properties of Opa proteins are maintained independent of the gonococcal strain; thus, the specificity for epithelial cells or leukocytes is intrinsic to Opa proteins. Significant homology exists in the surface exposed variable regions of two invasion supporting Opa proteins from independent strains. Efficient epithelial cell invasion is favoured by high level Opa production, however, a 10-fold reduction still allows significant invasion by gonococci. In contrast, recombinant Escherichia coli expressing Opa proteins adhered or invaded poorly under similar experimental conditions, thus indicating that additional factors besides Opa are required in the Opa-mediated interaction with human cells. PMID- 8440255 TI - Abscisic acid is involved in the iron-induced synthesis of maize ferritin. AB - The ubiquitous iron storage protein ferritin has a highly conserved structure in plants and animals, but a distinct cytological location and a different level of control in response to iron excess. Plant ferritins are plastid-localized and transcriptionally regulated in response to iron, while animal ferritins are found in the cytoplasm and have their expression mainly controlled at the translational level. In order to understand the basis of these differences, we developed hydroponic cultures of maize plantlets which allowed an increase in the intracellular iron concentration, leading to a transient accumulation of ferritin mRNA and protein (Lobreaux,S., Massenet,O. and Briat,J.F., 1992, Plant Mol. Biol., 19, 563-575). Here, it is shown that iron induces ferritin and RAB (Responsive to Abscisic Acid) mRNA accumulation relatively with abscisic acid (ABA) accumulation. Ferritin mRNA also accumulates in response to exogenous ABA. Synergistic experiments demonstrate that the ABA and iron responses are linked, although full expression of the ferritin genes cannot be entirely explained by an increase in ABA concentration. Inducibility of ferritin mRNA accumulation by iron is dramatically decreased in the maize ABA-deficient mutant vp2 and can be rescued by addition of exogenous ABA, confirming the involvement of ABA in the iron response in plants. Therefore, it is concluded that a major part of the iron induced biosynthesis of ferritin is achieved through a pathway involving an increase in the level of the plant hormone ABA. The general conclusion of this work is that the synthesis of the same protein in response to the same environmental signal can be controlled by separate and distinct mechanisms in plants and animals. PMID- 8440256 TI - An ATP transporter is required for protein translocation into the yeast endoplasmic reticulum. AB - The transfer of precursor proteins through the membrane of the rough endoplasmic reticulum (ER) in yeast is strictly dependent on the presence of ATP. Since Kar2p (the yeast homologue of mammalian BiP) is required for translocation, and is an ATP binding protein, an ATP transport system must be coupled to the translocation machinery of the ER. We report here the characterization of a transport system for ATP in vesicles derived from yeast ER. ATP uptake into vesicles was found to be saturable in the micromolar range with a Km of 1 x 10(-5) M. ATP transport into ER vesicles was specifically inhibited by 4,4'-diisothiocyanatostilbene-2,2' disulfonic acid (DIDS), a stilbene derivative known to inhibit a number of other anion transporters, and by 3'-O-(4-benzoyl)benzoyl-ATP (Bz2-ATP). Inhibition of ATP uptake into yeast microsomes by DIDS and Bz2-ATP blocked protein translocation in vitro measured co- as well as post-translationally. The inhibitory effect of DIDS on translocation was prevented by coincubation with ATP. Moreover, selective membrane permeabilization, allowing ATP access to the lumen, restored translocation activity to DIDS-treated membranes. These results demonstrate that translocation requires a DIDS and Bz2-ATP-sensitive component whose function is to transport ATP to the lumen of the ER. These findings are consistent with current models of protein translocation in yeast which stipulate the participation of Kar2p in the translocation process. PMID- 8440257 TI - Clathrin assembly protein AP180: primary structure, domain organization and identification of a clathrin binding site. AB - Binding of AP180 to clathrin triskelia induces their assembly into 60-70 nm coats. The largest rat brain cDNA clone isolated predicts a molecular weight of 91,430 for AP180. Two cDNA clones have an additional small 57 bp insert. The deduced molecular weight agrees with gel filtration results provided the more chaotropic denaturant 6 M guanidinium thiocyanate is substituted for the weaker guanidinium chloride. The sequence and the proteolytic cleavage pattern suggest a three domain structure. The N-terminal 300 residues (pI 8.7) harbour a clathrin binding site. An acidic middle domain (pI 3.6, 450 residues), interrupted by an uncharged alanine rich segment of 59 residues, appears to be responsible for the anomalous physical properties of AP180. The C-terminal domain (166 residues) has a pI of 10.4. AP180 mRNA is restricted to neuronal sources. AP180 shows no significant homology to known clathrin binding proteins, but is nearly identical to a mouse phosphoprotein (F1-20). This protein, localized to synaptic termini, has so far been of unknown function. PMID- 8440258 TI - Rab9 functions in transport between late endosomes and the trans Golgi network. AB - Rab proteins represent a large family of ras-like GTPases that regulate distinct vesicular transport events at the level of membrane targeting and/or fusion. We report here the primary sequence, subcellular localization and functional activity of a new member of the rab protein family, rab9. The majority of rab9 appears to be located on the surface of late endosomes. Rab9, purified from Escherichia coli strains expressing this protein, could be prenylated in vitro in the presence of cytosolic proteins and geranylgeranyl diphosphate. In vitro prenylated rab9 protein, but not C-terminally truncated rab9, stimulated the transport of mannose 6-phosphate receptors from late endosomes to the trans Golgi network in a cell-free system that reconstitutes this transport step. Rab7, a related rab protein that is also localized to late endosomes, was inactive in the in vitro transport assay, despite its efficient prenylation and capacity to bind and hydrolyze GTP. These results strongly suggest that rab9 functions in the transport of mannose 6-phosphate receptors between late endosomes and the trans Golgi network. Moreover, our results confirm the observation that a given organelle may bear multiple rab proteins with different biological functions. PMID- 8440259 TI - Sec dependent and sec independent assembly of E. coli inner membrane proteins: the topological rules depend on chain length. AB - Translocation of proteins across the inner membrane of Escherichia coli normally requires the participation of the sec machinery. A number of proteins are known, however, where translocation can proceed unhindered even when the function of either SecA or SecY, central components of the sec machinery, is blocked. We now show that there is a linear correlation between the length of a translocated region and its degree of dependence on SecA and SecY for lengths between 25 and 55 residues. We also find that positively charged residues have distinctly different topological effects during SecA dependent and SecA independent membrane protein insertion, and that a short cytoplasmic segment in Lep can be converted to a translocated segment (with a concomitant inversion of the original topology of the whole molecule) by increasing its length into the SecA/Y dependent realm. PMID- 8440260 TI - Membrane fusion of Semliki Forest virus in a model system: correlation between fusion kinetics and structural changes in the envelope glycoprotein. AB - This paper presents a kinetic analysis of low-pH-induced fusion of Semliki Forest virus (SFV) with cholesterol-containing unilamellar lipid vesicles (liposomes), consisting otherwise of phosphatidylcholine, phosphatidylethanolamine and sphingomyelin. Fusion is monitored continuously with a lipid mixing assay, involving virus bio-synthetically labeled with the fluorophore pyrene. At pH 5.55, 37 degrees C, SFV-liposome fusion occurs on the time scale of seconds. Extensive fusion (up to 60% of the virus) requires an excess of liposomes, while a low-pH preincubation of the virus alone results in inactivation of its fusion capacity. The onset of fusion after acidification of virus-liposome mixtures is preceded by a pH- and temperature-dependent lag phase. Early in this lag phase, a conformational change in the E2E1 spike glycoprotein occurs, involving formation of a trypsin-resistant E1 homotrimer, exposing a conformation-specific epitope (E1"). These changes are followed by a rapid, cholesterol-dependent binding of the virus to the liposomes (as assessed by sucrose density gradient analysis), subsequent fusion starting only after an additional delay. This sequence of events strongly suggests that the E1 homotrimeric structure represents the fusion active conformation of the SFV spike, the actual fusion complex possibly involving a higher order oligomer of E1 trimers. PMID- 8440261 TI - Divergent evolution of T cell repertoires: extensive diversity and developmentally regulated expression of the sheep gamma delta T cell receptor. AB - Sheep gamma delta T cells express an unprecedented repertoire of antigen receptors contributed by increased diversity in both variable and constant region gene segments. Variable region diversity results mainly from the utilization of a large family of duplicated V delta genes that have retained two distinct hypervariable segments comparable with the complementarity determining regions present in other antigen receptor V genes. This implies that sheep V delta chains have been intensely selected during evolution, probably at sites involved in ligand recognition. The sheep gamma delta heterodimer occurs in at least five isotypic variants formed by the association of a single C delta segment with one of five functional C gamma segments, each with distinctive hinge regions. Our analysis also shows that the establishment of a normal peripheral repertoire is both developmentally regulated and dependent on the continual presence of a functional thymus during ontogeny. The existence of an expanded V gene repertoire and multiple receptor isotypes together with the prominence of gamma delta T cells in the sheep immune system argues that this lineage of T cells has a more elaborate functional role in this evolutionary pathway. PMID- 8440262 TI - Biogenesis of von Willebrand factor-containing organelles in heterologous transfected CV-1 cells. AB - Von Willebrand factor (vWF) is a multimeric protein involved in the adhesion of platelets to an injured vessel wall. vWF is synthesized by the endothelial cell and the megakaryocyte as a precursor protein (pro-vWF) that consists of four repeated domains, denoted D1-D2-D'-D3-A1-A2-A3-D4-B1-B2-B3-C1-C2. Previously, we have defined the domains on the pro-vWF molecule involved in dimerization as well as the domains involved in multimer assembly of vWF dimers. In the endothelial cell, part of the vWF multimers is stored in specialized organelles, the Weibel Palade bodies. By using immunoelectron microscopy, we demonstrate that upon expression of full-length vWF cDNA, vWF-containing organelles are encountered in monkey kidney CV-1 cells that are morphologically similar to the endothelial specific Weibel-Palade bodies. Expression in CV-1 cells of a series of vWF cDNA deletion mutants, lacking one or more domains, revealed that only those vWF mutant proteins that are able to assemble into multimers are encountered in dense cored vesicles. Our data show that this process is independent of a particular domain on vWF and indicate that a 'condensed', multimeric vWF is required for targeting to the Weibel-Palade body. PMID- 8440263 TI - Association of p56lck with IL-2 receptor beta chain is critical for the IL-2 induced activation of p56lck. AB - Previous studies demonstrate that p56lck, a member of the src-family of protein tyrosine kinases (PTKs), can physically associate with the interleukin-2 (IL-2) receptor beta chain (IL-2R beta) and that IL-2 receptor engagement stimulates p56lck activity. To examine the mechanisms underlying p56lck PTK activation by IL 2, we established a mouse pro-B cell line, BAF-B03, expressing both IL-2R beta (either the wild-type or mutant forms) and mouse p56lck at high levels. BAF-B03 cells expressing a mutant IL-2R beta chain lacking an 'acidic' region of the cytoplasmic domain, previously shown to be essential for association with p56lck, fail to induce p56lck PTK activation upon IL-2 stimulation. This suggests that the association of p56lck with the IL-2R beta chain, despite its low stoichiometry, is required for the activation of cellular p56lck PTK upon IL-2 stimulation. Intriguingly, BAF-B03 cells expressing an IL-2R beta chain which lacks a different cytoplasmic region, the 'serine-rich' region, also fail to activate p56lck in response to IL-2. Hence, physical association of p56lck with the IL-2R beta chain is not by itself sufficient to permit IL-2-mediated regulation of this PTK. Additional experiments suggest that one result of PTK activation is the accumulation of c-fos and c-jun transcripts. PMID- 8440264 TI - cDNA cloning of MAP kinase kinase reveals kinase cascade pathways in yeasts to vertebrates. AB - A Xenopus 45 kDa protein has been identified as an immediate upstream factor sufficient for full activation of MAP kinase, and is shown to be capable of undergoing autophosphorylation on serine, threonine and tyrosine residues. In this study, we show that purified 45 kDa protein can phosphorylate a kinase negative mutant of Xenopus MAP kinase on tyrosine and threonine residues, suggesting that the 45 kDa protein functions as a MAP kinase kinase to activate MAP kinase. We then report the cloning and sequencing of a full-length cDNA encoding this 45 kDa MAP kinase kinase, and show that it is highly homologous to four protein kinases in fission and budding yeasts: byr1, wis1, PBS2 and STE7. These yeast kinases are therefore suggested to function as a direct upstream activator for a presumed MAP kinase homolog in each signal transduction pathway involved in the regulation of cell cycle progression or cellular responses to extracellular signals. Finally, we report bacterial expression of recombinant MAP kinase kinase that can be phosphorylated and activated by Xenopus egg extracts. PMID- 8440265 TI - Uptake and distribution of L-3-[I-125] iodo-alpha-methyl tyrosine in experimental rat tumours: comparison with blood flow and growth rate. AB - Radiolabelled amino acids combined with positron emission tomography (PET) show promise for the accurate delineation of viable tumour extent and may also provide a rapid and sensitive indicator of response to therapy. We have investigated the potential use of the radioiodinated amino acid analogue L-3-iodo-alpha-methyl tyrosine (IMT) for these purposes using experimental tumours in hooded rats. Preliminary studies using HSN tumours and IMT labelled with iodine-125 demonstrated maximum tumour uptake at 15 min post injection although an improved tumour-to-brain ratio was seen at 24 h due to the relatively poor retention of IMT in normal brain. Brain uptake of IMT was also found to be substantially reduced by competition with another large neutral amino acid phenylalanine; however, relatively less effect was seen in tumour, and in skeletal muscle no change in IMT uptake was observed. Quantitative autoradiography revealed no sign of heterogeneity in tumour IMT uptake: good penetration was seen even in poorly vascularised regions as confirmed by endothelial immunohistochemistry. Similar levels of IMT uptake were found in the OES.HR1 tumour during growth supplemented by exogenous oestrogen. Following arrest of tumour growth by removal of the oestrogen stimulus, IMT uptake was seen to fall from 1.7% to 1.0% of the injected dose per gram: this was matched by a fall in tumour blood flow as estimated by technetium-99m hexamethylpropylene amine oxime distribution. It appears that IMT uptake is more strongly influenced by blood flow than cell proliferation and that intratumoural distribution of IMT is principally determined by diffusion. PMID- 8440266 TI - Indium-111-labelled liposomes: dosimetry and tumour detection in patients with cancer. AB - Neutral phospholipid vesicles (VesCan), which had been prepared for clinical use, were loaded with 37 MBq indium-111 and administered to seven patients with malignant tumours. The median lipid dose was 2.0 mg/kg. Sequential images showed rapid blood clearance at the early stage, with homogeneous uptake of 111In labelled VesCan (111In-labelled V-liposomes) in the liver and spleen. Dosimetric estimates for these organs were 1.2 and 1.5 mGy/MBq, respectively, with a whole body exposure dose of 0.076 mGy/MBq. Total renal excretion of 111In was less than 10% of the injected dose, occurring mainly as 111In-EDTA in three patients. Gamma camera images 24-48 h after administration revealed increased activity in the tumours of four patients. 111In-labelled V-liposomes may enable the demonstration of the tumour site without toxicity and with radiation doses comparable to other radionuclide imaging techniques. PMID- 8440267 TI - The role of gallium-67 tumour scintigraphy in patients with small, non-cleaved cell lymphoma. AB - Two hundred and thirty-four scintigraphic studies were performed in 34 patients (27 men, 7 women, age 17.3 +/- 7.7 years) with small, non-cleaved cell lymphoma who had follow-up for 3-96 months (mean 21.6 +/- 21.7 months). Whole-body scintigraphy was performed 48-72 h following i.v. injection of 370 MBq gallium-67 citrate. "Gold standards" for truth determinations were surgery, autopsy, histology, axial x-ray computed tomography, magnetic resonance imaging, ultrasonography and clinical follow-up. Overall, 181 of 234 studies were true negative. Eighty proven sites of disease had true positive 67Ga uptake (in 21 patients/37 studies). Nineteen sites (in 12 patients/15 studies) were false positive. In addition, 31 benign lesions were detected and interpreted correctly in terms of non-malignancy. Ten lymphoma sites (in 6 patients/10 studies) were missed by scintigraphy. Overall, sensitivity of gallium scintigraphy was 89% when calculated by sites and 79% when calculated by studies. Corresponding specificities were 91% and 92%, respectively. Positive predictive values were 81% (sites) and 71% (studies), and negative predictive values 95% (sites and studies). Thus, gallium scintigraphy proved to be a sensitive and specific method for staging and follow-up in patients with small, non-cleaved cell lymphoma. PMID- 8440268 TI - Mechanism of thrombocytopenia in liver cirrhosis: kinetics of indium-111 tropolone labelled platelets. AB - Using indium-111 tropolone-labelled platelets, a study of platelet kinetics was performed on the basis of the relationship between platelet count, platelet survival time, platelet dynamics, platelet-associated immunoglobulin G (PA-IgG) and splenic volume in 31 patients with liver cirrhosis and a platelet count of less than 100 x 10(9)/l. The mean platelet count was 46.6 +/- 25.3 x 10(9)/l, and the mean platelet survival time was 6.50 +/- 1.33 days. The mean uptake into the spleen was 43.2% +/- 14.8% on the 1st day, and 53.7% +/- 14.3% on the 7th day. The mean PA-IgG level was 107.6 +/- 66.0 ng/10(7) platelets in five patients with chronic active hepatitis who were studied as controls, the mean platelet count was 197 +/- 30 x 10(9)/l, the mean platelet survival time 9.33 +/- 0.78 days, and the mean PA-IgG 21.2 +/- 2.9 ng/10(7) platelets. The former two parameters were significantly higher (P < 0.05), and the latter significantly lower (P < 0.05). In liver cirrhosis, the platelet count showed a positive correlation with the platelet survival time and a negative correlation with PA-IgG and the splenic volume. These results suggest that the increases in both the splenic platelet pool and platelet destruction in the spleen through immunological mechanisms may influence thrombocytopenia in liver cirrhosis. PMID- 8440269 TI - Iodine-123-labelled serum amyloid P component scintigraphy in amyloidosis. AB - This study describes the results of scintigraphy with iodine-123-labelled serum amyloid P component (SAP) as a means of establishing the distribution of organ involvement in amyloidosis. The significance of 123I-SAP scans obtained in 15 patients with biopsy-proven AA or AL amyloidosis is discussed. Biopsy-proven amyloidosis was typically confirmed by scintigraphy, though such confirmation was not obtained in the kidneys in six patients with histological proof of extensive renal amyloid deposition. This lack of uptake may have been due to the accumulation of a major part of the 123I-SAP in the spleen and/or liver. Twenty four hour whole-body retention of 123I-SAP was higher in patients with amyloidosis than in controls. Twenty-four hour tracer accumulation of the radioactivity in the extravascular compartment was notably greater in patients than in controls and appeared to be a good diagnostic criterion. We conclude that 123I-SAP scintigraphy may be helpful for the evaluation of organ involvement not only in patients with biopsy-proven amyloidosis but also when a biopsy cannot be performed or when a strong suspicion of amyloidosis exists in spite of repeated negative biopsies. PMID- 8440270 TI - Time sequential single photon emission computed tomography studies in brain tumour using thallium-201. AB - Time sequential single photon emission computed tomography (SPECT) studies using thallium-201 were performed in 25 patients with brain tumours to evaluate the kinetics of thallium in the tumour and the biological malignancy grade preoperatively. After acquisition and reconstruction of SPECT data from 1 min post injection to 48 h (1, 2, 3, 4, 5, 6, 7, 8, 9, 10 and 15-20 min, followed by 4-6, 24 and 48 h), the thallium uptake ratio in the tumour versus the homologous contralateral area of the brain was calculated and compared with findings of X ray CT, magnetic resonance imaging, cerebral angiography and histological investigations. Early uptake of thallium in tumours was related to tumour vascularity and the disruption of the blood-brain barrier. High and rapid uptake and slow reduction of thallium indicated a hypervascular malignant tumour; however, high and rapid uptake but rapid reduction of thallium indicated a hypervascular benign tumour, such as meningioma. Hypovascular and benign tumours tended to show low uptake and slow reduction of thallium. Long-lasting retention or uptake of thallium indicates tumour malignancy. PMID- 8440271 TI - Serial evaluation of left ventricular function by radionuclide ventriculography at rest and during exercise after orthotopic heart transplantation. AB - Discrepant results have previously been reported concerning long-term left ventricular function in the human transplanted heart as assessed by radionuclide ventriculography. In this study, radionuclide ventriculograms were obtained at rest and during exercise in 19 patients < 6 months, 7-12 months, 13-24 months and > 24 months after transplantation. Ejection fraction decreased significantly from < 6 months to 13-24 months after transplantation (rest: 69.1% +/- 9.7% to 56.7% +/- 8.3%, P < 0.05; exercise: 70.4% +/- 11.3% to 59% +/- 8%, P < 0.05). Heart rate increased significantly during exercise after > 2 years (90.2 +/- 10.5 beats/min to 103.5 +/- 15 beats/min, P < 0.05) but not within 6 months after transplantation (98.5 +/- 12.8 beats/min to 99.07 +/- 15.8 beats/min). Left ventricular end-diastolic volume remained unchanged. Peak filling rate at rest decreased significantly from 4.2 +/- 0.96 edv/s < 6 months after transplantation to 3.3 +/- 0.66 edv/s (P < 0.05) 13-24 months and 3.3 +/- 0.64 edv/s (P < 0.05) > 24 months after cardiac transplantation. Exercise peak filing rate did not change significantly. It is concluded that radionuclide ventriculography demonstrates a decrease in systolic left ventricular function in the long-term course after cardiac transplantation. A significant increase in exercise peak heart rate may be due to autonomic reinnervation. Differences in the literature concerning left ventricular function may be due to different observation intervals following cardiac transplantation. PMID- 8440272 TI - Significance of a hot spot on the bone scan after carpal injury--evaluation by computed tomography. AB - The use of bone scintigraphy in patients with negative radiographs after carpal injury is widely advocated. However, focally increased activity on the bone scan in the scaphoid or other carpal bones cannot always be radiologically confirmed as a fracture. To confirm scintigraphically suspected carpal fractures, computed tomography (CT) of the wrist was performed in patients with clinically suspected scaphoid fracture and initially negative radiographs. All patients underwent plain radiography, bone scintigraphy and CT. The combination of plain radiographs and CT, as judged by a panel of experienced observers, was used as the reference standard. In 18 patients, 21 out of 22 carpal hot spots on bone scintigraphy could be radiologically confirmed as a fracture. The diagnosis was missed by CT scan in three patients with proven fractures on plain radiographs. We conclude that, in patients with negative initial radiographs following carpal injury, a positive bone scan must be interpreted as a fracture. PMID- 8440273 TI - Active removal of radioactivity in the blood circulation using biotin-bearing liposomes and avidin for rapid tumour imaging. AB - In order to shorten the delay between the administration of tumour-imaging agents and obtainment of scintigrams, rapid delivery of radionuclide to tumours followed by rapid clearance from the blood is required. We used liposomes with biotin bound on their surface (B-liposomes) as carriers for rapid delivery. For rapid blood clearance, we employed avidin in the expectation that the strong affinity between biotin and avidin would result in the aggregation of B-liposomes in the blood circulation, and that these aggregates would be taken up rapidly by the reticuloendothelial system, resulting in the rapid elimination of liposomes and the radionuclide encapsulated in them. When B-liposomes encapsulating gallium-67 deferoxamine were intravenously administered to mice bearing sarcoma 180, large amounts of 67Ga were delivered to tumours by 4 h after injection, though the 67Ga blood level remained high. On the other hand, administration of avidin 4 h after administration of the B-liposomes dramatically reduced the blood level so that it was only 5% of that in the non-treated group 1 h later. As a result, the tumour to-blood ratio reached nearly 14 at 5 h after radionuclide administration, suggesting that rapid tumour-imaging will be feasible by means of this method. PMID- 8440275 TI - Lung scintigraphy: it could have been easier. PMID- 8440276 TI - Species and immunoglobulin preparation related effects on the biodistribution of technetium-99m-labelled immunoglobulin G in a baboon model. AB - Technetium-99m-labelled immunoglobulin G (99mTc-IgG) is a convenient and useful radio-pharmaceutical for the scintigraphic detection of inflammatory foci. However, unfavourable physiological biodistribution patterns such as high activities in the liver and especially in the kidneys impede the efficacy of this agent. This report describes biodistribution studies in the baboon model of various thiol reduction-mediated 99mTc-labelled immunoglobulins, including human IgG preparations (Sandoglobulin and Sigma: gamma-globulins prepared from Cohn fractions II and III) as well as baboon IgG preparations (Sigma: gamma-globulins prepared from Cohn fractions II and III and IgG isolated from the serum obtained from specific animals). The biodistribution studies demonstrated differences in kidney concentration, i.e. human IgG (Sandoglobulin) > baboon IgG (cross-over animal experiments with IgG isolated from the serum of the different animals) > human IgG (Sigma) approximately baboon IgG (Sigma) approximately baboon IgG (own IgG isolated from the serum of a specific animal, labelled with 99mTc and reinjected). Differences in liver concentration were also observed: human IgG (Sandoglobulin) < human IgG (Sigma) approximately baboon IgG (Sigma) approximately baboon IgG (own IgG) approximately IgG (cross-over). Characteristic were the relatively high activities in the liver and kidneys compared to those in other organs with high blood supply, and a relatively high retention in the blood pool.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8440274 TI - The value of lung scintigraphy in the diagnosis of pulmonary embolism. AB - The role of lung scintigraphy in the diagnostic management of patients with clinically suspected pulmonary embolism is reviewed. Evidence is provided that a normal perfusion scan excludes clinically relevant pulmonary embolism, and that a high probability lung scan, defined as a segmental perfusion defect with locally normal ventilation, sufficiently confirms the presence of pulmonary embolism in the majority of these patients. Furthermore, this review assesses the possibility of non-invasive tests for the diagnosis or exclusion of venous thromboembolic disease as a means of avoiding pulmonary angiography in patients with lung scan outcomes that are neither normal nor high probability. PMID- 8440277 TI - Enzymes of lysosomal origin in the cerebrospinal fluid and plasma of patients with multiple sclerosis. AB - Several lysosomal enzymes were determined in 47 and 62 samples of CSF and plasma, respectively, obtained from MS patients. CSF levels of most enzymes considered were significantly lower in patients when compared to those of the controls, whereas the plasma levels vary little and appeared to be influenced by the course of the disease. The most interesting result is the one concerning the beta-D glucuronidase in the plasma: in relapsing-remitting patients in the still untreated acute phase, the levels remain noticeably diminished in comparison to controls. The data suggest the potential of using this enzyme to monitor the progression of the disease. PMID- 8440278 TI - Unusual neuroradiological findings in systemic lupus erythematosus. AB - A 47-year-old woman affected by systemic lupus erythematosus (SLE) presented with headache, fever, splenomegaly and edema of the lower extremities. CT showed diffuse low density in the cerebral white matter and marked splenomegaly in the abdomen. T2-weighted MR images showed diffuse high intensity lesions in the white matter. After immunosuppressive therapy with prednisolone, there was marked improvement in the cranial CT and MR appearances. The underlying pathological process was probably edema secondary to a lupus microangiopathy. SLE can be complicated by a widespread abnormality of the white matter with marked radiological changes but few neurological signs. In the present case, only an episodic mild hemiparesis for 3 weeks without seizure and psychiatric disturbance was found neurologically during the whole clinical course. PMID- 8440279 TI - Seronegative myasthenia gravis and familial Hodgkin's disease. AB - A 29-year-old woman developed a seronegative myasthenia gravis. A thorax CT scan demonstrated an anterior mediastinal mass. Thoracotomy showed a lymphofollicular thymic hyperplasia and Hodgkin's disease of the nodular sclerosing type with mediastinal lymph node localisation. This patient's brother had been suffering as well from Hodgkin's disease. Epidemiological similarities (genetic influences and the role of a viral agent) between Hodgkin's disease and myasthenia gravis and the immune abnormalities found in these two diseases suggest that their association is not fortuitous. PMID- 8440280 TI - Oculomotor nerve palsy due to intraneural hemorrhage in idiopathic thrombocytopenic purpura: a case report. AB - We report a 52-year-old man with idiopathic thrombocytopenic purpura accompanying acute oculomotor nerve palsy. At autopsy, intraneural hemorrhage was found in the cavernous portion of the oculomotor nerve. Intraneural bleeding as well as extraneural compression by hematoma formation should be considered as a cause of neuropathies occurring in patients with aggravated thrombocytopenia. PMID- 8440281 TI - Failure to detect genomic material of HTLV-I or HTLV-II in mononuclear cells of Italian patients with multiple sclerosis and chronic progressive myelopathy. AB - To contribute to the undecided question if a retrovirus of the human T-cell lymphotropic virus (HTLV) family may be involved in the development of multiple sclerosis (MS), we investigated by the polymerase chain reaction (PCR) the presence of HTLV-I and HTLV-II sequences in the peripheral blood mononuclear cell DNAs from 30 patients affected by MS and 15 by chronic progressive myelopathy. Moreover a control group of 14 blood donors was examined. All these patients were devoid of anti-HTLV-I antibody in the serum and cerebrospinal fluid at ELISA. For the PCR, primers and probes specific for the tax region common to HTLV-I and HTLV II, for the pol region of HTLV-I, and for the pol region of HTLV-II were used. In spite of the high sensitivity of the technique used, the three groups of subjects were negative for HTLV-I and HTLV-II genomic sequences. PMID- 8440282 TI - A serial computerized tomographic study of the interval form of CO poisoning. AB - Serial computerized tomography (CT) was performed to quantitatively characterize cerebral changes in 1 case of the interval form of carbon monoxide poisoning. The patient was comatose for 2 days, regained consciousness for 8 days, and then developed akinetic mutism. During the remission period, a low-density area in the cerebral white matter was observed to enlarge progressively. These results suggest that the demyelination of the cerebral white matter progressed throughout the interval period. A correlation between changes in CT abnormalities and clinical presentation is described. PMID- 8440283 TI - Large and small coils in magnetic stimulation of the proximal portion of the facial nerve. AB - Magnetic stimulation (Magstim model 200) was performed with a large coil (14 cm in diameter) and a small coil (7 cm in diameter) in 12 healthy persons. Muscle potentials were obtained from ipsilateral orbicularis oris and nasalis muscles when magnetic stimulation was performed by placing a large or small magnetic coil at T6 or by placing a large magnetic coil at C4. The latency obtained by placing a magnetic coil at T6 was 1.2-1.3 ms (with a large coil) and 1.3-1.4 ms (with a small coil) longer, and the latency obtained by placing a large magnetic coil at C4 was 1.3-1.4 ms longer than the latencies obtained by stimulating at the stylomastoid foramen. The proximal portion of the facial nerve is considered to be stimulated transcranially when magnetic stimulation is performed by placing either a large or small coil at T6 or by placing a large coil at C4. PMID- 8440284 TI - Grading stenoses of the internal carotid artery by estimation of blood velocity with pulsed Doppler ultrasound. AB - The relationship between blood velocity and residual lumen diameter at the origin of 100 internal carotid arteries was studied. The diameter was measured by angiography and blood velocity by relatively simple Doppler ultrasound equipment. A scatter diagram between maximal velocity and diameter was used to construct a table on the sensitivity and specificity of various cutoff values for maximal velocity to diagnose stenoses of different degrees. A maximal velocity > or = 0.8 m/s had a sensitivity of 87% and a specificity of 93% to diagnose stenoses with a diameter < or = 3 mm (i.e. more than 50% diameter reduction). Thus, simple recording of maximal velocity can be used as a reliable screening method to detect patients with high- and medium-grade stenosis. Analysis of the spectral spreading of velocities across the lumen of a stenosis, or estimation of percent stenosis from the velocity in a stenosis and that in a poststenotic segment, were in our hands less useful for this purpose. None of the methods were good to detect or exclude the presence of low-grade stenosis. PMID- 8440285 TI - A neurophysiological study on the P300 component of event-related potentials in Hakim-Adams syndrome. AB - We have explored the variability of P300 event-related potentials in patients affected by Hakim-Adams syndrome, with raised or intermittent intracranial pressure, treated with surgical cerebrospinal fluid shunting. The clinical utility of P300 is confirmed in the light of the improvement of neurophysiological data after the surgical procedure, parallel with amelioration of neuropsychological performances. PMID- 8440286 TI - Extrapyramidal syndrome responsive to dopaminergic treatment following recovery from central pontine myelinolysis. AB - A 52-year-old woman developed severe hyponatremia following treatment for hypertension with chlorthalidone. Rapid correction of hyponatremia resulted in coma, quadriplegia and hypopnea compatible with central pontine myelinolysis. She recovered with residual facial hypomimia, bradykinesia, cogwheel rigidity and coarse resting tremor, responding to dopaminergic treatment. Her symptoms and signs, which are quite similar to idiopathic Parkinson's disease, are still responsive to treatment 7 years after onset. PMID- 8440287 TI - Dural arteriovenous fistula: a cause of hypoperfusion-induced intellectual impairment. AB - A 76-year-old, right-handed man developed posttraumatic dural arteriovenous fistula (DAVF) involving the superior sagittal sinus. He developed slow but progressive intellectual deterioration and gait disturbance after a minimal head trauma. Cerebral angiography demonstrated a DAVF of the superior sagittal sinus with sinus thrombosis supplied by branches of the bilateral external carotid arteries, and a DAVF of the right sigmoid sinus supplied by the right occipital artery. Selective embolization was carried out. He showed marked improvement on neuropsychological testing, especially on test items which are supposed to tap functions of the right cerebral hemisphere which showed an improved cerebral blood flow. We concluded that the intellectual impairment of our patient was caused by cerebral hypoperfusion, especially of the right cerebral hemisphere. PMID- 8440288 TI - Polymyositis associated with asymptomatic primary biliary cirrhosis. AB - We studied a 67-year-old female who suffered from polymyositis associated with primary biliary cirrhosis (PBC). Liver dysfunction was revealed by a screening test. Antimitochondrial antibodies (AMA) and antinuclear antibodies were positive. Liver biopsy was compatible with PBC (Scheuer stage I). Four years later she showed severe weakness and atrophy on her four extremities. Laboratory examination showed a creatinine kinase level of 312 IU/l, IgM 416 mg/dl, and AMA titer 1:320. Muscle biopsy findings were compatible with polymyositis. Electron microscopic examination disclosed diffuse increase of mitochondria in subsarcolemma and intermyofibrils, which has not been reported until now in polymyositis associated with PBC. PMID- 8440289 TI - Infantile mitochondria encephalomyopathies: report on 4 cases. AB - Four muscle biopsies from the quadriceps femoris muscle of children with symptoms suggesting mitochondrial encephalomyopathy were examined for morphological and biochemical differences. From a biochemical point of view, our patients showed a derangement of mitochondrial metabolism and in particular a marked deficit in the activity of cytochrome c oxidase. In all patients there was an abnormally high rise of lactate and pyruvic acid levels in blood before and after glucose loading. Results of morphological and enzyme histochemical studies showed smaller muscle fibre diameters than in normal children. Typical red ragged fibres and ultrastructural abnormalities in muscle mitochondria were present in 1 case only. Three patients showed focal changes in the distribution of some sarcoplasmic oxidative enzyme activities. The present findings suggest that the main metabolic disorder, pointed out by biochemical studies, is scarcely reflected by morphological and ultrastructural studies in the early stages of mitochondriopathies. PMID- 8440290 TI - Inverted Bruns' nystagmus in arachnoid cysts of the cerebellopontine angle. AB - A 9-year-old girl with huge, double arachnoid cysts at the cerebellopontine angle is reported. After a cyst-peritoneal shunt operation, she developed fine, high frequency gaze nystagmus towards the lesion side combined with coarse, large amplitude nystagmus in the opposite direction, which is the reverse of the Bruns' nystagmus. We call this reverse phenomenon 'inverted' Bruns' nystagmus. As the nystagmus disappeared after a second shunt operation, the nystagmus was presumed to be caused by the cystic lesion. PMID- 8440291 TI - The latencies of sympathetic skin responses. AB - The sympathetic skin response (SSR) was measured in 35 normal healthy adults and in 40 patients with diabetic polyneuropathy. When recording from the hand or the foot, the SSR latency was the same whether stimulating at the hand or the foot. This may suggest that the conduction velocity of afferent fibers is much faster than that of efferent fibers, so that the former do not contribute to the SSR latency. The SSR amplitudes were significantly reduced in diabetic patients (p < 0.001), but their latencies were normal as long as responses could be detected. It is possible that some surviving unmyelinated fibers and/or regenerated fibers take the responsibility for normal conduction. Another possible explanation is that the postganglionic unmyelinated fibers in polyneuropathy may represent themselves as 'all or none', i.e., either the fibers conduct with normal velocity or they do not conduct at all. PMID- 8440292 TI - Plasma levels of levodopa and its main metabolites in parkinsonian patients after conventional and controlled-release levodopa-carbidopa associations. AB - The paper reports plasma levels of levodopa (LD), its main metabolites [dopamine, dihydroxyphenylacetic acid, homovanillic acid, 3-O-methyldopa (3-O-MD)] and carbidopa in 14 parkinsonian patients first treated with Sinemet and thereafter with Sinemet-CR4. A good relationship was observed between LD plasma levels and pharmacological effects. While the LD area under the curve increased after Sinemet-CR4, the same was not observed with metabolites, except with 3-O-MD. The experiments in volunteer subjects confirmed the increase in 3-O-MD in plasma after Sinemet-CR4. Higher levels were observed also in the CSF with a reduction of LD concentrations. This seems to corroborate the hypothesis of an interference with LD passage through the blood-brain barrier in humans. PMID- 8440293 TI - Bilateral medial medullary infarction: magnetic resonance imaging and correlative histopathologic findings. AB - Bilateral medial medullary infarction is a rare event which clinically presents with flaccid tetraplegia sparing the face, bilateral disturbance of deep sensation, hypoglossal nerve palsy and respiratory failure. We here report a patient with such symptoms in whom magnetic resonance imaging enabled the detection of signal abnormalities in the lower brainstem as soon as 9 h after onset. Results of a control study 3 weeks later correlated well with the extent of infarction that was seen at autopsy. Early lesion detection in the lower medulla by magnetic resonance imaging and the unfavorable prognosis of patients with ischemic damage at that location may provide the rationale for aggressive therapeutic strategies in such a condition. PMID- 8440294 TI - Water metabolism and postconcussional symptoms 5 weeks after mild head injury. AB - Posttraumatic diabetes insipidus has been reported as a sequela to head injury. It is unknown whether subclinical types of diabetes insipidus, or other types of water metabolism disorders, occur after mild head injury (MHI) and, if so, whether they are related to the persistence of postconcussional symptoms. MHI patients (n = 38) were screened for disturbances of water metabolism by comparing plasma and urine osmolalities at about 5 weeks after the trauma. Eight patients had evidence of an increased plasma osmolality together with a relatively decreased urine osmolality after an overnight fast. The presence of this disturbance was significantly related to the persistence of postconcussional symptoms. The results suggest that subclinical disturbances of water metabolism may, among other factors, be related to the persistence of symptoms after MHI. PMID- 8440295 TI - The interval between the positive peak of premyoclonus spike and the onset of myoclonus is shorter than the cortical latency in cortical myoclonus. AB - In 6 patients with cortical myoclonus, the intervals between the positive peak of the premyoclonus cortical spike and the onset of the myoclonic jerk [interval (Sp Mcl)] were precisely measured by the computer-assisted jerk-locked averaging method. The intervals (Sp-Mcl) were 13.0-15.8 ms for the abductor pollicis brevis, 8.0-10.4 ms for the extensor digitorum communis and 5.5 ms for the biceps brachii, respectively. These were apparently shorter than the normal latencies of the responses elicited by transcranial cortical stimulation. The difference between the interval (Sp-Mcl) and the spinal latency was -0.8 to 3.5 ms, which was not long enough for the time required for the descending volleys going down from the cortex to the spinal cord. We have concluded that the motor cortex is activated before the positive peak of the premyoclonus spike in cortical myoclonus. PMID- 8440296 TI - Fatal hemorrhage during anticoagulation of cardioembolic infarction: role of cerebral amyloid angiopathy. AB - We report a patient with recurrent cardioembolism and hemorrhagic infarcts, who developed a fatal intracerebral hemorrhage 3 days after intravenous anticoagulation. At autopsy, cerebral amyloid angiopathy (CAA) was found. Because CAA and anticoagulation may add up to trigger cerebral hemorrhage, the possibility of underlying CAA should be raised before anticoagulating elderly patients with stroke. PMID- 8440297 TI - Peripheral facial nerve paralysis after local upper dental anaesthesia. AB - A 50-year-old female patient developed a facial nerve paralysis after a local upper dental block. This complication is known to occur after an inferior dental block but has only sporadically been reported after local anaesthetic procedures in the upper jaw for dental treatment. Some possible pathogenetic mechanisms are discussed. PMID- 8440298 TI - Open enrollment and students with disabilities: issues, concerns, fears, and anticipated benefits. AB - Open enrollment is a hotly debated form of educational choice. More than 25 states have legislation establishing or expanding public school choice options. At an issues clarification working session, professionals, legislators, policymakers, parents, and students described issues and generated implications for serving students with disabilities. Participants identified three kinds of issues for districts and students: outcome, implementation, and demographic. Participants also expressed other concerns about choice: pupil benefit, parent involvement (or convenience), teacher/administrator job protection, change, and teacher workload. PMID- 8440299 TI - The perceived environment of special education classrooms for adolescents: a revision of the classroom environment scale. AB - The Classroom Environment Scale (CES), originally developed for use in traditional public school classrooms, was revised for use in special education classrooms. The scale, which assesses students' perceptions of various aspects of the classroom, was administered to students in 79 special education classrooms in 16 residential and day treatment schools serving special education students with behavior disorders and emotional disturbance. Psychometric analyses showed that only seven of the nine aspects of the classroom found in the original CES were reliably reported in special education classrooms. The revised scale was found reliable for use in special education classes in residential and day treatment settings. PMID- 8440300 TI - "Flat" versus "weighted" reimbursement formulas: a longitudinal analysis of statewide special education funding practices. AB - Tennessee data were analyzed longitudinally from 1979-80 to 1987-88 in terms of numbers of children placed in a variety of service options. In 1983-84, the Tennessee funding formula was changed from a "flat" rate to a "weighted" formula. The weighted formula was associated with a statistically significant decrease in less restrictive placements and a reliable increase in more restrictive placements. A statewide survey of district special education directors suggested that service needs may have been more likely than monetary incentives to explain the observed changes. PMID- 8440301 TI - Integrated learning: explicit strategies and their role in problem-solving instruction for students with learning disabilities. AB - This study investigated the effectiveness of an explicit strategy as a means of linking facts, concepts, and problem solving in an unfamiliar domain of learning. Participants were 37 secondary students with learning disabilities. All students were taught health facts and concepts, which they then applied to problem-solving exercises presented through computer-simulation games. Students in the experimental group were taught an explicit strategy for solving the problems; the comparison group was given supportive feedback and encouraged to induce their own strategies. The explicit strategy group performed significantly better on two transfer measures, including videotaped problem-solving exercises. PMID- 8440302 TI - Beyond Section 504: satisfaction and empowerment of students with disabilities in higher education. AB - College and university students with disabilities were surveyed to determine their levels of satisfaction with accessibility, special services, and accommodations at their schools. In addition, students were requested to identify barriers to postsecondary education, improvements in services, and other concerns. Respondents generally expressed satisfaction with the services that they had received. However, the majority indicated that they had encountered barriers to their education, including a lack of understanding and cooperation from administrators, faculty, staff, and other students; lack of adaptive aids and other resources; and inaccessibility of buildings and grounds. Recommendations were made for improving the delivery of services and self advocacy of students with disabilities. PMID- 8440303 TI - Identification and characterisation of angiotensin II receptor subtypes in human brain. AB - Autoradiographic and homogenate binding studies using the radioligand, [125I]angiotensin II, identified a heterogeneous distribution of specific binding sites (defined by angiotensin II, 1.0 microM) throughout the human forebrain. Highest AT receptor densities were detected in the paraventricular nucleus, median eminence, substantia nigra, putamen and caudate nucleus (2.4, 1.2, 1.0, 0.30 and 0.24 fmol/mg tissue equivalent, respectively). The AT1 receptor antagonist, losartan (1.0 microM) competed for the majority of the specific binding. [125I]Angiotensin II-specific binding (although not consistently above non-specific binding levels) was also detected in various other brain regions (e.g. amygdala, entorhinal cortex, frontal cortex, hippocampus, inferior colliculus, nucleus accumbens, parietal cortex, periaquaductal grey, superior colliculus, striate cortex, temporal cortex, thalamus). In the presence of losartan (1.0 microM), angiotensin II, saralasin, losartan and PD123177 competed for [125I]angiotensin II binding to membranes prepared from the cerebellum or substantia nigra with a rank order of affinity; angiotensin II = saralasin > PD123177 > losartan. In the presence of PD123177 (1.0 microM), the rank order of affinity of losartan and PD123177 was reversed. These studies indicate the presence of both AT1 and AT2 receptor subtypes within various regions of the human forebrain. PMID- 8440304 TI - Effect of temperature on limitation by MK-801 of firing of action potentials by spinal cord neurons in cell culture. AB - The anticonvulsant, MK-801, limited sustained high frequency repetitive firing of sodium-dependent action potentials by mouse spinal cord neurons in monolayer dissociated cell culture. Limitation was voltage- and temperature-dependent and was accompanied by decreasing rate of rise of action potentials until firing ceased during the 400 ms depolarizations. The IC50 for limitation was 2 x 10(-7) M at 37 degrees C, 6.4 x 10(-7) M at 35 degrees C, and 4 x 10(-5) M at 23 degrees C. The relationship between the percentage of neurons capable of sustained repetitive firing and MK-801 concentration at 33 degrees C was biphasic. The first phase (about 50%) of limitation had IC50a = 1.5 x 10(-7) M, and the second had IC50b = 2 x 10(-4) M; the midpoint of the connecting plateau was 10(-5) M. At temperatures below 37 degrees C, the current needed to achieve maximal firing increased. The maximal rate of rise, maximal firing frequency and sensitivity to MK-801 of action potentials elicited by 1 ms stimuli decreased at temperatures below 37 degrees C. Passive membrane properties were unchanged. Slow firing and a temperature-sensitive conformational change in voltage-activated sodium channels could account for the higher concentrations of MK-801 required to block sodium dependent action potentials at temperatures below 37 degrees C. PMID- 8440305 TI - Differential effects of ceruletide on amphetamine-induced behaviors and regional dopamine release in the rat. AB - This study concerned the effects of ceruletide, a cholecystokinin (CCK)-related peptide, on amphetamine-stimulated behaviors (hyperlocomotion and stereotypy) and amphetamine-induced dopamine (DA) release from the striatum and the nucleus accumbens of the rat. Also, behavioral alterations due to ceruletide administration were compared with the change in DA release from these areas. Ceruletide 160 micrograms/kg s.c., attenuated hyperlocomotion induced by amphetamine, 1 mg/kg and 3 mg/kg s.c., but had no effect on amphetamine-induced stereotypy. Results from in vivo microdialysis experiments showed that s.c. administration of ceruletide caused a significant inhibition of the amphetamine induced increase in DA release in the nucleus accumbens but not in the striatum. These neurochemical inhibitory effects of ceruletide disappeared completely with bilateral subdiaphragmatic vagotomy. However, infusion of 1 microM of ceruletide into the nucleus accumbens through the dialysis probe had no effect on amphetamine-induced DA release. These results suggest that the inhibitory effect of peripheral administration of ceruletide on amphetamine-induced hyperlocomotion is closely related to the change in DA release from the nucleus accumbens. In the nucleus accumbens, systemically administered ceruletide acts initially on the peripheral organs and influences the activity of DA terminals via an unknown path related to the vagus. Ceruletide had different actions on the dopaminergic system in the striatum and that in the nucleus accumbens. PMID- 8440306 TI - Morphine depresses the transmission of noxious messages in the spino(trigemino) ponto-amygdaloid pathway. AB - We had recently demonstrated that a subregion of the parabrachial area relays nociceptive information in the spino(trigemino)-ponto-amygdaloid pathway. The aim of the present study was to investigate, in halothane-anesthetized rats, the effect of i.v. administration of morphine on nociceptive specific neurons located in the parabrachial area with some cells being antidromically driven from the amygdala. Morphine induced a marked depression of responses elicited by noxious thermal stimuli (waterbath, 50 degrees C) dose relatedly (1, 3, 9 mg/kg) and naloxone reversibly, with an ED50 = 1.8 mg/kg. This effect of morphine probably not only reflects the direct action of this drug at the spinal level, but could also involve a direct action at the parabrachial level. These results could account at least in part for the effect of morphine on the emotional-affective aspects of pain. PMID- 8440307 TI - Endothelin antagonizes the hypotension and potentiates the hypertension induced by clonidine. AB - Modification of clonidine-induced cardiovascular effects by endothelin-1 (ET-1) was studied in male Sprague-Dawley rats. A dose-dependent decrease in blood pressure and heart rate was produced by clonidine (100, 250 and 500 micrograms/kg i.v.). Lower doses produced only a fall in blood pressure (through central alpha adrenoceptors) while higher doses of clonidine produced an initial hypertensive response (through peripheral alpha-adrenoceptors) and subsequent longer lasting hypotension and bradycardia. The hypotension and bradycardia induced by 100 and 250 micrograms/kg i.v. dose of clonidine were completely blocked by ET-1 (100 ng/kg i.v.) pretreatment. Conversely, the hypertensive response induced by high dose of clonidine (500 micrograms/kg i.v.) was significantly potentiated by ET-1 pretreatment. In cervical sectioned rats, i.v. administered clonidine failed to produce any hypotensive effect, indicating lack of central effect of clonidine. ET-1 significantly (P < 0.0005) potentiated the hypertensive response of a low dose (50 micrograms/kg i.v.) of clonidine in cervical-sectioned rats. I.c.v. administration of clonidine (1, 2, 4 and 6 micrograms) produced a dose-dependent decrease in blood pressure and heart rate. ET-1 pretreatment (25 ng i.c.v.) transiently blocked the clonidine-induced decrease in blood pressure and heart rate for about 10 min but the hypotension and bradycardia was observed subsequently. Since the major site of action of clonidine is the ventral surface of medulla, clonidine was applied directly to the ventral surface of medulla and produced a decrease in blood pressure and heart rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8440308 TI - Ca2+ channel antagonists inhibit the intestinal absorption of digoxin in the guinea-pig. AB - Simultaneous administration of digoxin and Ca2+ channel antagonists results in an increased plasma level of digoxin. A possible mechanism underlying this interaction might be the influence of Ca2+ channel antagonists on the enteral absorption of digoxin. To study this interaction, two groups of experiments were performed with guinea-pigs. In the first group, the influence of Ca2+ channel antagonists on the rate of enteral absorption of digoxin in vivo was studied. In the second group, the influence of Ca2+ channel antagonists on the transfer of digoxin through the wall of the isolated everted small intestine in vitro was investigated. The intravenously determined minimal lethal dose of digoxin 30 min after its intraduodenal administration was increased in animals pretreated with either verapamil, diltiazem, nifedipine or nicardipine. Addition of either verapamil or diltiazem to the solution on the mucosal side of isolated everted small intestine sacs decreased the transfer of digoxin through the intestinal wall. Similar results obtained in both groups indicate that, under our experimental conditions, Ca2+ channel antagonists inhibit the enteral absorption of digoxin in the guinea-pig. PMID- 8440309 TI - Milacemide effects on the temporal inter-relationship of amino acids and monoamine metabolites in rat cerebrospinal fluid. AB - The temporal inter-relationship of various amino acids and monoamine metabolites in rat cerebrospinal fluid was examined after acute administration of milacemide (100, 200 or 400 mg/kg i.p.), a glycine prodrug. Glycine concentrations rose linearly and dose dependently (20-190%) but were only significantly elevated at the higher milacemide dose (200 and 400 mg/kg). In animals given 400 mg/kg, glycine values were still significantly elevated 8 h later. A concomitant increase (20-25%) in serine and taurine and a decrease in alanine cerebrospinal fluid values were observed at the highest milacemide dose. Other amino acids were unaffected. While cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations were unaffected, the dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, exhibited a linear dose-dependent reduction. However, only homovanillic acid values were significantly decreased after 400 mg/kg milacemide. Cerebrospinal fluid analysis may be useful as a first screen in ascertaining putative neurochemical changes associated with drug administration. PMID- 8440310 TI - Further studies on ocular responses to DP receptor stimulation. AB - Prostaglandin D2 (PGD2) and the selective DP receptor agonist BW 245C have been previously shown to lower intraocular pressure in rabbits, while PGD2, but not BW 245C, caused plasma extravasation, eosinophil infiltration, and goblet cell depletion. In these present studies definition of the ocular pharmacology of prostaglandin D2 (PGD2) has been extended by using a further selective DP receptor agonist SQ 27986 and a potent and selective DP receptor antagonist BW A868C. In cats and rabbits SQ 27986 caused ocular hypotension. The ocular hypotensive effect of PGD2 in rabbits was blocked by pretreatment with the DP receptor antagonist BW A868C, whereas the activities of PGE2 and PGF2 alpha remained unaltered. The singular involvement of the DP receptor in changes in rabbit intraocular pressure evoked by PGD2 was thereby verified by using the antagonist BW A868C. In terms of effects on the ocular surface, SQ 27986 caused no increase in conjunctival microvascular permeability, no eosinophil infiltration, and no depletion of the goblet cell population. These findings reinforce the concept that selective DP receptor agonists may be useful for lowering intraocular pressure without causing ocular surface pathology. PGD2 induced increases in conjunctival microvascular permeability were inhibited by BW A868C, despite the fact that DP receptor agonists failed to evoke a plasma exudation response. This finding was unexpected and suggests a possible subdivision of the DP receptor designation. PMID- 8440311 TI - The influence of prostaglandins on the contractile response to electrical field stimulation in rabbit myometrial and cervical smooth muscles. AB - Indomethacin (10 microM) significantly reduced the contractile responses to electrical field stimulation (EFS) in the non-pregnant myometrium (5-50 Hz by an average of 25.7%) and the pregnant myometrium (30-50 Hz by an average of 16.5%). On the other hand, it significantly increased the contractile responses of the cervix in non-pregnant (2.5-30 Hz by an average of 21.5%) and pregnant (2.5-10 Hz by an average of 12.5%) muscular strips. Prostaglandin (PG) E2 (0.1-1000 nM) strongly and PGI2 (0.1-1000 nM) slightly and dose-dependently inhibited the contractile response to EFS of the non-pregnant cervical muscle, but not of the myometrium. In the pregnant uterus, the contractile responses of the cervical muscle were similar to those of the non-pregnant cervix, while the response of the myometrium was increased significantly and dose-dependently by the application of PGE2 or PGI2.PGF2 alpha (1000 nM) significantly increased the contractile response of the myometrium but not cervical muscle to EFS in the pregnant rabbits. In non-pregnant muscles, the contractile responses of the myometrium and cervical smooth muscle to EFS were not influenced by the treatment with PGF2 alpha.PGE2 (0.1-1000 nM) also inhibited the contractile response to direct muscle stimulation, but the inhibition was significantly less than that of the response to indirect stimulation. PGI2 slightly inhibited the contractile responses to both indirect and direct stimulation. These findings indicate that PGE2, PGI2 and PGF2 alpha increase the contractile response of pregnant myometrium to EFS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8440312 TI - Heterogeneous responses of substantia nigra pars reticulata neurons to gamma hydroxybutyric acid administration. AB - The effect of intravenous administration of gamma-hydroxybutyric acid (GHB) (50 400 mg/kg) on the firing rate of substantia nigra pars reticulata (SN-PR) neurons was studied by making single cell extracellular recordings in unanesthetized rats. For comparison, the effect of intravenous muscimol (0.5-2 mg/kg) and ethanol (0.5-2 g/kg) was also studied. GHB produced variable effects: dose related inhibition in 7 out of 18 (38.8%) neurons and no significant change in 11 out of 18 (61.2%) neurons tested. In contrast, muscimol and ethanol produced a dose-related inhibition of the SN-PR firing rate. The results indicate that GHB, unlike muscimol and ethanol, has no profound effect on the activity of SN-PR neurons, and thus disinhibition of dopaminergic units, through inhibition of SN PR neurons, is probably not the mechanism by which GHB stimulates the firing rate of dopaminergic neurons. PMID- 8440313 TI - Effects of phencyclidine, MK-801 and 1,3-di(2-tolyl)guanidine on non-dopaminergic midbrain neurons. AB - The effects of i.v. administration of the noncompetitive NMDA receptor antagonists, phencyclidine and MK-801, and the sigma receptor ligand, 1,3-di(2 tolyl)guanidine (DTG), on the firing rates of non-dopaminergic mid brain neurons were evaluated in chloral hydrate-anesthetized rats. Phencyclidine and MK-801 inhibited the activity of putative gamma-aminobutyric acid (GABA)-containing interneurons identified by their response to foot-pinch. DTG did not significantly alter neuronal activity. These results suggest that the reported excitatory effects of non-competitive NMDA receptor antagonists on dopamine neuronal activity are due, in part, to disinhibition secondary to the inhibition of interneuron activity. PMID- 8440314 TI - Does 5-carboxamidotryptamine-induced turning in guinea-pigs involve 5-HT1D autoreceptors? AB - Contralateral turning induced by unilateral injection of 5-carboxamidotryptamine (5-CT) into guinea-pig substantia nigra could result from unilaterally reduced inhibition of the dopaminergic pathway as a consequence of a decreased release of inhibitory 5-hydroxytryptamine (5-HT) through stimulation of 5-HT1D autoreceptors. This hypothesis was tested by administering 5-CT unilaterally to freely moving guinea pigs through a microdialysis probe, and simultaneously measuring extracellular 5-HT in the dialysate and rotation. A concentration of 250 mN 5-CT was required to produce significant turning. This also induced a massive increase in extracellular 5-HT, introduced as an impurity of the 5-CT. The presence of high concentrations of extracellular 5-HT makes it unlikely that 5-CT-induced rotation is mediated through decreased 5-HT release resulting from 5 HT1D autoreceptor stimulation. PMID- 8440315 TI - The non-depolarizing D-form of bromohomoibotenic acid enhances depolarizations evoked by the L-form or quisqualate. AB - The D-enantiomer of bromohomoibotenic acid (Br-HIBO) was inactive in electrophysiological experiments when administered alone, but enhanced depolarizations evoked by L-Br-HIBO or quisqualate when co-administered with these agonists. In addition, quisqualate induced a long-lasting (> 120 min) sensitization of cortical wedge neurons to D-Br-HIBO. This latter effect of D-Br HIBO was similar to, but significantly more potent and selective, than the earlier observed quisqualate-induced sensitization of cortical neurones to depolarization by (S)-2-amino-4-phosphonobutyric acid (L-AP4). PMID- 8440316 TI - Nematolysosomes (elongate lysosomes) in rat hepatocytes: their distribution, microtubule dependence, and role in endocytic transport pathway. AB - The distribution of lysosomes in rat hepatocytes was examined by three dimensional electron microscopy combined with acid phosphatase (ACPase) cytochemistry. In the 2-microns-thick sections observed under 200- or 1000-kV TEM, it was apparent that ACPase activity localized on elongate lysosomes (we refer to them as nematolysosomes) with a diameter of 70-100 nm and lengths of several micrometers, as well as spherical lysosomes and trans-Golgi cisternae. Though most spherical lysosomes were located within the pericanalicular region, nematolysosomes were widely distributed throughout the hepatocytes. Typically, it appeared that the nematolysosomes elongated from the subsinusoidal region to the pericanalicular-Golgi complex area and they frequently formed a network at the cell periphery along the sinusoidal front. Furthermore, the formation of nematolysosomes was independent of new protein synthesis, but highly dependent on the integrity of microtubules. After a 6-8 h colchicine treatment, nematolysosomes were shrunk and/or fragmented, becoming roughly spherical lysosomes scattered throughout the cells. Nematolysosomes recovered their normal profiles after 24 h due to the reversible effect of the drug on microtubules. When the hepatocytes were exposed to horseradish peroxidase (HRP) in vitro or in vivo, HRP was quickly sequestered in nematolysosome-like structures via pinocytosis from the sinusoidal surface and transported to an area near the Golgi complex. These findings raise the possibility that the nematolysosomes engage in microtubule-dependent transport of macromolecules from the sinusoidal circulation to the Golgi complex area. PMID- 8440317 TI - Chromatin fibers with different protamine and histone compositions. AB - Previous studies have established that chromatin fibers which contain histones have variable diameters in different biological materials. In this paper we show that chromatin fibers are also present in spermatozoa and spermatids of bivalve molluscs in which some or all histones have been replaced by protamines. In all cases thick chromatin fibers are formed, with a diameter in the range 25-50 nm, depending on the species. We conclude that the formation of chromatin fibers is determined by the partial neutralization of the DNA charges with any histone or protamine, rather than due to a precise association of nucleosomes. This conclusion is in agreement with current theoretical work which shows that the diameter of complexes of DNA with counterions is determined by an overall balance of the interaction forces present. PMID- 8440318 TI - Ara-C treatment leads to differentiation and reverses the transformed phenotype in a human rhabdomyosarcoma cell line. AB - Rhabdomyosarcoma (RMS) is an embryonal tumor of childhood that arises from primitive skeletal muscle-forming cells (rhabdomyoblasts) probably arrested and transformed along the normal myogenic pathway to maturation. Since Ara-C is an antitumor agent known to induce differentiation in human acute myelogenous leukemia, also presumably a disorder of cellular maturation, we treated RD, a human embryonal RMS cell line, with Ara-C and evaluated its effect on growth and differentiation. Ara-C treatment of RD cells in vitro caused a dose-dependent growth inhibition in the absence of cytotoxicity. Interestingly, RD cells treated with 5 x 10(-7) M Ara-C for 4 days were able to recover logarithmic growth after the removal of the drug from the media. A reexposure of these cells to Ara-C led to morphological and biochemical changes related to differentiation, including the appearance of an increased number of multinucleated cells that expressed muscle-specific actin and skeletal muscle myosin heavy chain (MHC) (fast). In vivo studies demonstrated that RD cells pretreated with 5 x 10(-7) M Ara-C lost their ability to form tumors in nude mice. We conclude that treatment of this human embryonal RMS cell line with Ara-C results in marked growth inhibition in vitro, loss of tumorigenicity in vivo, and the expression of biochemical markers present in a more differentiated phenotype. These data suggest a potential role for differentiation therapy as a therapeutic approach in RMS. PMID- 8440319 TI - Detection of a novel sepiapterin reductase mRNA: assay of mRNA in various cells and tissues of various species. AB - Fragments of cDNA coding for rat, murine, and human sepiapterin reductase (SR) were amplified by PCR via primer positioning close to the reported 3'-end of the coding region in the rat enzyme. They were sequenced and used as probes for mRNA detection. Northern blot analysis detected two mRNA species for SR. Their sizes were 1.3 and 2.1 kb for rat, 1.3 and 2.3 kb for mouse, and 1.6 and 2.1 kb for human cell lines. Comparison of rat cell lines and rat tissues indicated that in tissues only the 1.3-kb species is present. Washing of the Northern blots under different stringency conditions indicated a more stable interaction of the 1.3-kb mRNA species with the cDNA probe as compared to the 2.3-kb species. The 1.3-kb species corresponds to the reported 28.2-kDa molecular mass of rat SR monomer. SR mRNA expression is absent in the human NK-like cell line YT and in the murine erythroleukemia subclone B8/3, which both lack SR activity. Moreover, the relative mRNA expression correlates with the enzymatic activities of different cell lines within the same species. This indicates that SR activity is regulated by its steady state mRNA levels. PMID- 8440320 TI - A high-affinity binding protein for the regulatory subunit of cAMP-dependent protein kinase II in the centrosome of human cells. AB - In the human lymphoblastic cell line KE 37, Northern blot analysis with cDNA probes for human regulatory subunits RII alpha RII beta of the cAMP-dependent protein kinase (A-kinase) type II and immunoblotting or immunoprecipitation studies with several antibodies directed against RII alpha and RII beta show that these two isoforms are expressed. The major isoform alpha is mostly cytosolic, whereas the beta isoform appears concentrated in the Golgi-centrosomal area, as judged by immunofluorescence and cell fractionation. Using a 32P-labelled RII overlay on Western blots, a 350-kDa RII-binding protein (AKAP 350) was specifically identified in centrosomes isolated from this cell line, whereas a Golgi fraction has previously been demonstrated to contain an 85-kDa RII-binding protein (AKAP 85). AKAP 350 is highly insoluble and can partially be extracted from centrosomes as a complex of AKAP 350 and RII subunit. AKAP 350 was identified as a specific centrosomal protein previously demonstrated in the pericentriolar material. The potential significance of a specific subcellular distribution for different RII-binding proteins in nonneuronal cells is discussed. PMID- 8440321 TI - Regulated expression of the MRP8 and MRP14 genes in human promyelocyticleukemic HL-60 cells treated with the differentiation-inducing agents mycophenolic acid and 1 alpha,25-dihydroxyvitamin D3. AB - The calcium-binding proteins MRP8 and MRP14 present in mature monomyelocytic cells are induced during differentiation and may mediate the growth arrest in differentiating HL-60 cells. We determined the levels of a protein complex (PC) containing MRP8 and MRP14 and investigated the mechanism by which the genes encoding these proteins are regulated in HL-60 cells treated with the differentiation-inducing agent mycophenolic acid (MPA). While the PC was barely detectable in untreated cells, MPA treatment resulted in elevated levels of the PC which were maximal at 3-4 days and were found to directly parallel gains in the steady-state levels of MRP8 and MRP14 mRNA. Transcription studies with the use of nuclear run-on experiments revealed increased transcription initiation at the MRP8 and MRP14 promoters after MPA treatment. 1 alpha,25-Dihydroxyvitamin D3, which induces HL-60 cell differentiation by another mechanism, was also found to increase transcription initiation at the MRP8 and MRP14 promoters. Our results suggest that this initiation is the major control of maturation agent-mediated increases in MRP8 and MRP14 gene expression, and supports a role for the PC in terminal differentiation of human monomyelocytic cells. PMID- 8440322 TI - Localization of basic fibroblast growth factor in bovine endothelial cells: immunohistochemical and biochemical studies. AB - To gain insight into the mechanisms of synthesis, storage, and release of basic fibroblast growth factor (bFGF), we studied the immunohistochemical localization of bFGF in bovine coronary artery, coronary sinus, and adrenal capillary endothelial cells grown in culture. Light and electron microscopic immunohistochemical studies were performed using the ABC immunoperoxidase method on p-formaldehyde-fixed cells. Five different anti-bFGF antibodies gave similar results in all cell types. In subconfluent cells, immunoreactivity was noted in the nuclear chromatin, nucleoli, cytosol, cytoplasmic vesicles (some of which appeared to fuse with the plasma membrane), and extracellular matrix. No reaction was found in endoplasmic reticulum or Golgi zones. Confluent cells demonstrated less immunoreactivity in the nuclei and cytosol but more in the extracellular matrix. Some cells of senescent morphology showed only cytoplasmic staining; however, no cells were found with only nuclear staining. Biochemical studies showed that three forms of bFGF (18, 24, and 26 kDa) were present in endothelial cells and varied with different culture conditions. Protection analysis indicated that bFGF mRNA is less abundant in postconfluent cells than in subconfluent cells. These data suggest that subconfluent cells synthesize bFGF and transport it into the nucleus and exocytotic vesicles, while confluent cells synthesize little bFGF but store it in extracellular matrix, cytoplasmic vesicles, and nuclei. PMID- 8440323 TI - Definition of the roles for iron and essential fatty acids in cell cycle progression of normal human T lymphocytes. AB - A serum-free cell culture system for human T lymphocytes was used to investigate the synthesis and metabolism of several important cell cycle-regulated proteins (p62c-fos, p110Rb, and p34cdc2 and its homologs) and the possible roles of iron and essential free fatty acids in regulating cell cycle progression. Following stimulation with phorbol dibutyrate (PDB) and ionomycin under serum-free conditions, resting T cells entered the cell cycle, as evidenced by a burst of synthesis of p62c-fos and an increase in the amount of the p33 homolog of the cdc2 kinase. However, in the absence of other additions, cells were arrested in the G1 phase of the cell cycle. Supplementation of the medium with two components, iron and linoleic acid (LA), permitted activated cells to progress through the G1 phase of the cycle and initiate DNA synthesis. Under these conditions p110Rb became phosphorylated and p34cdc2 was synthesized similar to T cells proliferating in normal serum-containing medium. The addition of iron, without LA, had little effect on activated cells; however, the addition of LA, in the absence of added iron, had profound effects. RNA accumulated to levels characteristic of cells at the G1/S interface, phosphorylation of p110Rb was almost complete, and p34cdc2 was synthesized, although at lower levels than in proliferating cells. However, no DNA synthesis was detected; under these conditions the cells appeared to be blocked at or near the G1/S border. Since there was a possibility that some component of the cell culture system could provide "trace" amounts of iron, and also to further delineate the role of iron in this system, cells were activated in medium containing LA and deferoxamine (10 microM), a chelator of iron. The accumulation of p34cdc2 was now reduced to nearly undetectable levels although phosphorylation of p110Rb was not substantially affected. It therefore appears that synthesis of p34cdc2 requires a low amount of iron, a finding which may define a possible regulatory point in the cell cycle for iron before its well-recognized role in regulating S phase entry by acting as a cofactor for the enzyme ribonucleotide reductase. PMID- 8440324 TI - Dihydrocytochalasin B enhances transforming growth factor-beta-induced reexpression of the differentiated chondrocyte phenotype without stimulation of collagen synthesis. AB - Rabbit articular chondrocytes were treated with retinoic acid (RA) to eliminate the differentiated phenotype marked by the synthesis of type II collagen and high levels of proteoglycan. Exposure of such cells to transforming growth factor-beta 1 (TGF-beta 1) in secondary culture under serum-free and RA-free, defined conditions led to reexpression of the differentiated phenotype. The microfilament modifying drug, dihydrocytochalasin B (DHCB), enhanced the effectiveness of TGF beta 1 and produced a threefold stimulation of type II collagen reexpression (measured by 2-D CNBr peptide mapping) at 0.3 ng/ml TGF-beta 1 without altering total collagen synthesis. Type II collagen reexpression was maximal from 1 to 5 ng/ml TGF-beta 1, with or without DHCB. The effect of DHCB on proteoglycan synthesis was maximal at 1 ng/ml TGF-beta 1. At this dose TGF-beta alone produced no increase in 35SO4 incorporation, while simultaneous treatment with DHCB caused a sevenfold stimulation of proteoglycan synthesis. DHCB-independent stimulation proteoglycan reexpression occurred between 5 and 15 ng/ml TGF-beta 1. In contrast, TGF-beta 1-dependent stimulation of proteoglycan synthesis in differentiated chondrocytes in primary monolayer culture was not substantially affected by DHCB. The collagen data suggest that TGF-beta 1 utilizes separate pathways to control phenotypic change and collagen (matrix) synthesis. Microfilament modification by DHCB selectively enhances the effectiveness of the TGF-beta 1-dependent signaling pathway that controls reexpression of the differentiated phenotype. PMID- 8440325 TI - System for quantitation of gene expression in single cells by computerized microimaging: application to c-fos expression after microinjection of anti-casein kinase II antibody. AB - A system which allows sensitive and fast automated analysis of weakly labeled fluorescent specimens is described. It is tested in the analysis of c-fos expression stimulated by fetal calf serum and calibrated by quantitation of defined solutions injected into cells with the automated microinjection system. Low light level imaging technology combined with quantitative image processing methods and computer control of the hardware allows fully automated analysis of fluorescent molecules in single living or fixed cells. Reliable methods for subtraction of fluorescent background and automated identification of objects of interest in double-stained cells are described. The accuracy of quantitation is considerably improved by normalizing the fluorescence intensities of respective fluorophores in the same object by the method of ratio imaging. The error rate in determining the relative protein content in single cells is less than 15%. The method is applied to microinjection studies with a monoclonal antibody against casein kinase II subunit beta. Microinjection of this antibody into synchronized cells specifically inhibits c-fos expression stimulated by fetal calf serum. In combination with the computer-automated capillary microinjection system, the technique will become a useful tool in experiments requiring quantitative single cell analysis. PMID- 8440327 TI - Expression of basement membrane proteins: evidence for complex post transcriptional control mechanisms. AB - Differentiated murine teratocarcinoma cell lines have been widely used as sources for the basement membrane proteins laminin and collagen IV. In order to understand the control of their expression, we have measured the transcription rates of the corresponding genes in nuclear run-on assays. The ratios of transcripts obtained from the five different genes of interest (for laminins A, B1, and B2 and alpha 1(IV), alpha 2(IV)) are rather different from the ratios of the corresponding mRNAs, which are again different from the protein levels needed. The gene for alpha 2(IV) is transcribed at a higher rate than the one for alpha 1(IV) and, similarly, the gene for laminin A is transcribed at a higher rate than the other two laminin genes, respectively. However, the alpha 2(IV) and laminin A mRNA levels are lower than those for the other chains of the same molecule. The alpha 1(IV) mRNA is 3- to 15-fold more abundant than the alpha 2(IV) mRNA, depending on the cell line. At the protein level, the A chain seems to be limiting for the assembly of laminin, in accordance with its low mRNA level. The two collagen chains have variable pool sizes, but the triple helical molecules always seem to be composed of two alpha 1(IV) and one alpha 2(IV) chains. These results point to extensive control mechanisms at various stages of posttranscriptional events, some of which we could identify. PMID- 8440326 TI - Cell motility, invasion, and malignancy induced by overexpression of K-FGF or bFGF. AB - We have tested the hypothesis that fibroblast growth factors contribute to cell locomotion and invasion, by investigating the properties of NIH-3T3 fibroblasts that secrete K-FGF following transfection with the K-fgf proto-oncogene and NIH 3T3 fibroblasts transfected with either the normal basic fibroblast growth factor (bFGF) coding sequence that lacks a known secretory signal sequence, or a chimeric bFGF sequence fused to an immunoglobulin signal sequence that targets the growth factor to the secretory pathway. The cell lines were tested for altered invasive characteristics on a physiologically relevant collagen substratum, and their motility rates were measured in cell locomotion assays using time-lapse video microscopy in the absence or presence of suramin, an inhibitor of growth factor-receptor interaction. The data were analyzed by comparing the motility rates of all K-fgf- and bFGF-transfected cell lines as a function of malignant potential. These studies show for the first time that K-fgf gene expression potently increases cell motility characteristics. Further, the bFGF transfectants generally exhibited increased rates of cell locomotion which were not dependent upon the presence of a signal sequence for secretion. These results support models of cell locomotion in which stimulation of this process can occur through both autocrine and intracrine pathways. In addition, a significant correlation was found to exist between cell locomotion and malignant potential, supporting the view that growth factor-induced motility, although not sufficient on its own to induce metastasis, is important in the promotion of tumor cell dissemination. PMID- 8440328 TI - The coupling between transforming growth factor-alpha and the epidermal growth factor receptor during rat liver regeneration. AB - Transcriptional and post-transcriptional regulation of hepatic expression of the epidermal growth factor receptor (EGF-R) and its autocrine ligand, transforming growth factor-alpha (TGF-alpha), were analyzed during liver regeneration. The EGF R mRNA levels were about twofold induced at 3 h after hepatectomy, caused by transcriptional activation. This was immediately followed by a decrease, reaching a low at half the initial level after 18 h, due to a decreased transcriptional rate. TGF-alpha mRNA expression was detected in normal liver using solution hybridization analysis. Concurrent with the decrease in EGF receptors, an increase of the TGF-alpha mRNA level occurred, starting at 6 h after hepatectomy and peaking at twice the initial TGF-alpha mRNA level after 12-24 h. For TGF alpha, however, no increase in the rate of gene transcription could be detected. TGF-alpha and EGF competed for binding to the same hepatic receptor in normal as well as in regenerating liver. TGF-alpha bound to a similar number of binding sites as EGF in both control and 18-h posthepatectomy livers, but with 4-5 times lower affinity than EGF. At 18 h posthepatectomy, the number of binding sites was reduced to about 55% for both ligands. When the subcellular distribution of endocytosed 125I-labeled TGF-alpha was compared with that of 125I-labeled EGF, no differences were observed, and furthermore, no changes were observed in the subcellular distribution of 125I-labeled TGF-alpha during liver regeneration. The distinct and coordinate regulation of the two interactors, EGF-R and TGF-alpha, suggests that the EGF-receptor system may be functionally involved in the different phases of the prereplicative growth stimulatory process during liver regeneration. PMID- 8440329 TI - CDGF (chicken embryo fibroblast-derived growth factor) is mitogenically related to TGF-beta and modulates PDGF, bFGF, and IGF-I action on sparse NIH/3T3 cells. AB - Chicken embryo fibroblast (CEF)-derived growth factor (CDGF), which was recently isolated from serum-free conditioned medium (SFCM) of confluent primary cultures of CEF (A. Geistlich and H. Gehring, Eur. J. Biochem. 207, 147-153, 1992), exhibited a strong mitogenic activity on sparse cultures of NIH/3T3 cells. The activity of CDGF was different from that of SFCM; i.e., the onset of DNA synthesis was delayed for about 7 h. CDGF induced maximally 25% of the activity of serum or SFCM if the activity was measured with a 2-h[3H]thymidine pulse starting 15 h after stimulation of the cells, indicating loss of a protein which modulated the mitogenic activity of CDGF. However, [3H]-thymidine incorporation of cells stimulated with approximately 50 pM CDGF reached serum values after prolongation of the thymidine pulse to 24 h. PDGF, at a concentration of approximately 300 pM, and bFGF (approximately 10 pM) exhibited strong activities in the 2-h pulse, whereas TGF-beta behaved like CDGF. IGF-I induced [3H]thymidine incorporation only weakly and only in the 2-h pulse. EGF did not induce any [3H]thymidine incorporation at all. CDGF together with small concentrations of bFGF (3.5 pM), higher concentrations of PDGF (300 pM), or IGF-I (1 nM) increased synergistically thymidine incorporation in the 2-h pulse, exceeding in the case of PDGF and bFGF the values obtained with 10% serum. Such a synergism could not be demonstrated with alpha-fetoprotein or fetuin, two serum proteins which have been reported to cooperate with growth factors. Regarding induction of cellular growth, only PDGF proved similar to serum, whereas cells stimulated with CDGF or TGF-beta showed a decreased rate of multiplication during the first day after stimulation. After this lag, however, CDGF- and TGF-beta-stimulated cells grew also with a rate similar to that obtained with serum, indicating the induction of an autocrine mitogen by CDGF or TGF-beta. FGF, IGF-I, and PDGF all enhanced CDGF induced cell growth during the first day, whereas an additive stimulation over at least 2 days was observed with PDGF. CDGF behaved similar to TGF-beta in the synergism with IGF-I. PMID- 8440330 TI - Measurement of cell-monolayer adhesion in cells transfected with N-CAM cDNAs. AB - To measure the adhesion of cells expressing the neural cell adhesion molecule N CAM, mouse Lmtk- fibroblast cells were transfected by a calcium phosphate precipitation technique with eucaryotic expression vectors encoding N-CAM polypeptides. We obtained cell lines expressing the 140-kDa transmembrane isoform of N-CAM at high levels by several rounds of selection by fluorescence-activated cell sorting and compared the adhesion of these cells to that of untransfected cells using a centrifugal removal assay that measures the centrifugal force required to remove radiolabeled probe cells from a cell monolayer. The adhesion of cells prepared from embryonic chicken neural retinas also was examined. Retinal probe cells remained associated with a retinal cell monolayer with an adhesive force of approximately 5 x 10(-6) dyn/cell, and this force was not reduced by treatment with specific anti-N-CAM antibody fragments. Transfected and untransfected mouse L cells each were dislodged from transfected cell monolayers with a removal force of 5 x 10(-5) dyn/cell and thus did not differ in their adhesion. These results support the hypothesis that N-CAM-mediated homophilic adhesion in retinal cells and transfected fibroblasts is relatively weak and that the major adhesive interaction involved in N-CAM-mediated cell-cell adhesion is heterophilic. PMID- 8440331 TI - Inhibition of chemotactic peptide-induced development of cell polarity and locomotion by the protein kinase C inhibitor CGP 41 251 in human neutrophils correlates with inhibition of protein phosphorylation. AB - Several protein kinase inhibitors of the staurosporine type displaying different enzyme specificity were used to study the role of protein kinase C (PKC) in motile neutrophil functions. Effects on protein phosphorylation, F-actin localization, morphology, and locomotion were determined. Only staurosporine, but not another inhibitor more specific for PKC (CGP 41 251) or inhibitors of cyclic nucleotide-dependent kinases (KT 5720, KT 5822), induced formation of F-actin enriched surface protrusions at nanomolar concentrations in initially spherical neutrophils. The inhibitor with the highest specificity for PKC, CGP 41 251, had no effect on morphology and F-actin localization of resting cells up to 1 microM. However, this inhibitor suppressed front-tail polarity and locomotion in chemotactic peptide-stimulated cells. The cells became nonpolar with surface projections instead. Inhibition of front-tail polarity induced by CGP 41 251 strongly correlated with inhibition of in situ phosphorylation of a 67-kDa protein (IC50 = 0.2 microM), whereas induction of polarity by chemotactic peptide was associated with increased phosphorylation of this protein. Kinase inhibitors inactive on PKC (KT 5720, KT 5822) did not affect development of front-tail polarity. We conclude that a kinase involved in the phosphorylation of a 67-kDa protein, very likely a PKC isoform, may be important for the development of cell polarity and locomotion. In contrast, chemotactic peptide-induced formation of actin-containing protrusions may not be mediated by this enzyme. PMID- 8440332 TI - Motch A and motch B--two mouse Notch homologues coexpressed in a wide variety of tissues. AB - Notch is one of the neurogenic genes of Drosophila controlling the decision between ectodermal and neural fate for cells in the early embryo. We have used a polymerase chain reaction (PCR)-based strategy to identify cDNA clones representing two mouse homologues to the Drosophila Notch gene. One of the genes, Motch A, is the mouse orthologue to the previously cloned Notch genes in Xenopus, rat, and man. The other gene, Motch B, is more distantly related to the characterized vertebrate Notch genes, but of equal homology to the Drosophila Notch as is Motch A, and therefore represents a distinct branch of a vertebrate Notch gene family. The Motch A and Motch B branches probably arose by gene duplication early in vertebrate evolution. Both Motch A and Motch B retain the same principal structure, encode mRNAs of approximately 10 kilobases, are expressed during mouse embryogenesis, and have largely overlapping expression patterns in adult tissues. We discuss possible consequences of expressing two closely related Notch homologues in the same set of tissues in terms of cell-cell signaling and differentiation control. PMID- 8440333 TI - Inhibition of EGF-induced signal transduction by microgravity is independent of EGF receptor redistribution in the plasma membrane of human A431 cells. AB - Epidermal growth factor (EGF)-induced c-fos and c-jun expression is strongly suppressed in microgravity. We investigate here whether this is due to inhibition of processes occurring during the initiation of EGF-induced signal transduction. For this purpose, EGF-induced receptor clustering is used as a marker. The lateral distribution of EGF receptors is directly visualized at an ultrastructural level by the label-fracture method. Quantification of the receptor distributions shows that EGF-induced receptor redistribution is similar under normal and microgravity conditions. This suggests that microgravity influences EGF-induced signal transduction downstream of EGF binding and EGF receptor redistribution, but upstream of early gene expression in human A431 cells. PMID- 8440334 TI - U1 and U2 snRNA are localized in the sperm nucleus. AB - Analysis of epididymal rat sperm RNA strongly suggested the presence of U snRNAs, especially U1 and U2 snRNA. By Northern blot analysis with radiolabeled oligodeoxynucleotide probes, the presence of U1 and U2 snRNA in rat sperm was confirmed. To precisely localize these RNAs, in situ hybridization with antisense and sense oligo probes labeled with digoxigenin was carried out. The results indicate that U1 as well as U2 snRNA are confined to the sperm nucleus. PMID- 8440335 TI - DIF-resistant expression of a prespore-specific gene in Dictyostelium in vitro development. AB - In submerged culture, the prespore-specific gene, D19, of Dictyostelium discoideum was found to be expressed in the early stages of development, even in the presence of 1 nM of DIF-1 (stalk differentiation inducing factor). This concentration of DIF-1 later caused the degradation of the previously accumulated D19 mRNA concomitant with the induction of the prestalk-specific genes ecmA/ecmB and eventually 85% of cells differentiated into stalk cells. These results suggest that prespore differentiation occurs at least transiently even in the presence of DIF-1. PMID- 8440336 TI - Exposure to low frequency pulsed electromagnetic fields increases interleukin-1 and interleukin-6 production by human peripheral blood mononuclear cells. AB - The exposure of human peripheral blood mononuclear cells to extremely low frequency pulsed electromagnetic fields (PEMFs) increased both the spontaneous and the PHA- and TPA-induced production of interleukin-1 (IL-1) and IL-6. Our results suggest that cells of the monocytic lineage, which are good producers of both IL-1 and IL-6, can be important cellular targets for PEMFs. Taking into account that these cytokines are among the most pleiotropic ones, these data can help us understand the previous reported effects of PEMFs on the proliferation of human lymphocytes and the effects exerted by such fields on cartilage and bone cells, whose physiological activity is highly dependent on IL-1 and IL-6. PMID- 8440337 TI - Regulation of erythropoietin production. PMID- 8440338 TI - Interleukin-3 followed by GM-CSF for delayed engraftment after autologous bone marrow transplantation. AB - Recombinant human interleukin-3 (IL-3) is well-tolerated according to phase I studies, and produces trilineage hematologic responses in patients with normal bone marrow. In addition, promising results have been obtained in a variety of bone marrow failure states. We studied IL-3 in 7 patients with markedly delayed engraftment after autologous bone marrow transplantation (ABMT) for hematologic malignancies (acute myeloid leukemia 4, chronic myeloid leukemia 1, myeloma 1, non-Hodgkin's lymphoma 1). All patients were red blood cell- and platelet transfusion-dependent, had an absolute neutrophil count (ANC) < 0.7 x 10(9)/L and failed to achieve a sustained ANC > 1.0 x 10(9)/L after receiving granulocyte macrophage colony stimulating factor (GM-CSF) for 28 days. IL-3 was given daily for 21 days at 2 micrograms/kg/d (2 patients) and 5 micrograms/kg/d (5 patients). Toxicity was mild and consisted mostly of low-grade fever and malaise. No changes in platelet, hemoglobin or reticulocyte levels were observed. Four patients had at least a 2-fold increase in ANC at the end of IL-3 treatment. Five patients received GM-CSF 10 micrograms/kg/d subcutaneously for 7 to 10 days immediately after IL-3 and 4 had a further increase in ANC (median 1.7-fold, range 1.6- to 5.8-fold), but no change in platelet transfusion requirements. Hematopoietic colony assays of bone marrow cells obtained before and after treatment showed that granulocyte-macrophage colony-forming cell (CFU-GM) and erythroid blast forming cell (BFU-E) levels were severely reduced and multilineage progenitors (CFU-GEMM) absent in all patients, and remained low after IL-3 treatment for 21 days. Sequential IL-3 and GM-CSF produced a significant but transient increase in the neutrophil counts of some patients. IL-3 appears to be of limited benefit in patients who are severely aplastic after ABMT and have very low levels of bone marrow progenitors. PMID- 8440339 TI - Compensatory mechanisms in platelet production: lack of a paracrine response in W/Wv mice treated with 5-fluorouracil. AB - W/Wv mice maintain normal platelet levels despite having a reduced functional stem cell pool, indicating that platelet production in these mice is compensated by altered megakaryocytopoiesis. In this study the effect of 5-fluorouracil (5 FU) treatment on platelet production in W/Wv mice and their congenic normal littermates was assessed. Recovery of circulating platelet levels occurred 11 days after 5-FU administration in W/Wv mice and subsequently did not increase above control values. In contrast, normal littermates showed an increased platelet count by day 8 and significant thrombocytosis between days 11 and 14. Investigation of bone marrow megakaryocytopoiesis in W/Wv mice showed there was no recovery in the number of megakaryocyte progenitors (CFU-Meg) per femur between days 3 and 5, but control values were reached by day 10. In addition, by day 8 the number of mature megakaryocytes per unit volume of bone marrow in these mice had not returned to control values, although the megakaryocytes were of an increased size. In comparison, the number of CFU-Meg per femur in normal mice treated with 5-FU began to recover after day 3, returned to control values by day 8 and increased to supranormal levels by day 14. Bone marrow megakaryocyte concentration was increased 2-fold over the control by day 8 and an increase in mean megakaryocyte size was also observed. The data suggest that platelet production in mice is dependent on the rate of establishment of both the progenitor cell and megakaryocyte pools. The inability of W/Wv mice to enhance and accelerate progenitor cell levels led to a reduced bone marrow response and failure to produce a marked thrombocytosis. PMID- 8440340 TI - A specific chromosomal deletion in murine leukemic cells induced by radiation with different qualities. AB - G-banded metaphase chromosomes prepared from 14 male CBA/Ca mice with histologically confirmed myeloid leukemia (ML) were studied in an effort to identify specific chromosomal changes associated with radiation leukemogenesis. The chromosome studies were undertaken as part of a larger investigation of radiation carcinogenesis, in which mice were exposed to radiation of several different qualities, i.e., x-rays, gamma-rays and "monoenergetic" fast neutrons of 5 mean energies ranging from 0.2 to 14 MeV. The 14 ML cases showed no histologically phenotypic differences and they were transplantable in syngeneic mice. We detected a specific chromosomal deletion in 1 copy of mouse chromosome 2 at regions D-E in all radiation-induced ML cells, regardless of radiation quality. Our results strongly implicate the involvement of genes within or close to regions D-E of chromosome 2 in radiation leukemogenesis. In addition to the specific deletion in chromosome 2, loss or gain of the Y chromosome was also detected in some cells from 6 ML cases. Because this hypo- or hyperploidy occurred in only a small fraction of leukemic cells, a causative role in radiation leukemogenesis appears unlikely. PMID- 8440341 TI - Quantitation of murine hematopoietic stem cells in vitro by limiting dilution analysis of cobblestone area formation on a clonal stromal cell line. AB - Murine hematopoietic stem cells with varying proliferative capacity can be assayed by limiting dilution analysis of "cobblestone area" (CA) formation on stromal layers in microlong-term bone marrow cultures. Cobblestone area forming cell (CAFC) frequency determined at early time points (day 7) correlates with mature stem cells measured as day 8 CFU-S, whereas CAFC frequency determined at day 28 correlates more closely with long-term marrow repopulating ability. Here we report a modification of the CAFC assay in which a clonal bone marrow stromal cell line, GB1/6, is substituted for fresh marrow-derived stromal layers. This modification simplifies the initial culture setup, eliminates inhomogeneities in the stromal layer and reduces the need for mice. Normal bone marrow CAFC frequencies were the same for both types of stromal cell underlayer, demonstrating the ability of a clonal cell line to completely replace the heterogeneous microenvironment of fresh stroma for in vitro stem cell support. PMID- 8440342 TI - Bilineage hematopoietic inhibitor and T lymphocyte dysfunction in a patient with pure red cell aplasia, myasthenia gravis and thymoma. AB - The case history, laboratory findings and clinical course of a patient with pure red cell aplasia (PRCA) combined with myasthenia gravis and thymoma are reported herein. In vitro study revealed bilineage complement-dependent IgG inhibitor(s) in both the granulocyte-macrophage and erythroblastic progenitor cells. His serum showed high anti-acetylcholine receptor antibody levels associated with activity of myasthenia gravis as well as PRCA. Patient history of thymectomy 7 years previously followed by extensive cutaneous candidiasis with abnormal T lymphocyte subsets (decreased T4/T8 ratio and increased number of activated T lymphocytes) in both the bone marrow and peripheral blood suggested primary T lymphocyte dysfunction, whereas the erythropoiesis was not inhibited by T lymphocytes. This case is of interest in the context of a possible immunological pathogenesis for other hematopoietic disorders, including some cases of aplastic anemia. PMID- 8440343 TI - Substituted purines elicit differential cytokinetic, molecular and phenotypic effects in HL-60 cells. AB - This study investigated and compared the cytokinetic, phenotypic and molecular effects elicited in HL-60 human leukemic cells by low doses (0.6 microM) of 3 closely related, substituted purines, puromycin (PM), puromycin aminonucleoside (PAN) and 6-dimethylaminopurine (6-DMAP). PM, but not 6-DMAP or PAN, inhibited [14C]leucine incorporation, induced a time-related cytotoxic effect, a G2-arrest, a metaphase-mitotic-arrest, apoptosis and c-myc mRNA superinduction. PAN and 6 DMAP exerted no detectable morphological or cytokinetic effects, although exposure to these drugs resulted in downregulation of c-myc mRNA levels. We suggest that the specific effects exerted by PM relate to the generation of nascent peptidyl-PM complexes by PM, but not by 6-DMAP or PAN. PMID- 8440344 TI - Cellular and cytokine dependent monocyte-mediated leukemic cell death: modulation by interferon-gamma and tumor necrosis factor-alpha. AB - Activated human monocytes and macrophages are involved in host defense against neoplastic cells. In view of cellular adoptive immunotherapy, we have studied the role of tumor necrosis factor-alpha (TNF-alpha) and gamma-interferon (IFN-gamma) in monocyte-mediated cytotoxicity on the level of both effector and leukemic target cells. Highly purified and IFN-gamma-activated monocytes were cytolytic to U937 cells up to 81.9 +/- 5.3% (mean +/- SEM) in a 24-hour MTT cytotoxicity assay at an effector-to-target-cell ratio of 10. Upon IFN-gamma activation these monocytes showed a 20-fold increase in TNF-alpha secretion of 663 +/- 122 pg/mL. Comparable concentrations of recombinant human TNF-alpha showed only cytostatic effects on U937 cells of approximately 20% after 24 hours, similar to the cytostatic effects of IFN-gamma-activated monocyte culture supernatants. These effects could be fully reversed by anti-TNF-alpha antibodies. U937 cells pretreated with TNF-alpha were almost completely resistant to monocyte-mediated cytotoxicity, supernatant-mediated cytostasis and to TNF-alpha up to 10(4) U/mL. IFN-gamma-activated monocytes were able to lyse TNF-alpha-modified U937 cells whereas IFN-gamma-activated monocyte supernatants showed only cytostatic activity after prolonged incubation. Additionally, target cell modulation by IFN-gamma potentiated the TNF-alpha-dependent cytolytic and cytostatic effects of monocytes, monocyte culture supernatants and TNF-alpha. We conclude that monocytes as a cellular component in monocyte-mediated cytotoxicity are far more potent in lysis of leukemic target cells than are secreted monokines. Furthermore, IFN-gamma and TNF-alpha are involved in the regulation of the susceptibility of leukemic cells for lysis by interactions with monocytes. PMID- 8440345 TI - Characterization of stroma-adherent colony-forming cells: a clonogenic assay for early hemopoietic cells? AB - Hemopoietic cells that adhered to preformed selected marrow stromal cell layers were characterized on the basis of progenitor cell production capacity, colony formation kinetics and forward light scatter (FLS) properties. It was shown that early hemopoietic cells attached to the stromal layers within 2 hours of incubation, and were responsible for the initial production of the more differentiated granulocyte-macrophage colony-forming cells (day 14 GM-CFC) in long-term cultures (LTC). In a clonogenic assay system, hemopoietic cells that adhere to stromal layers can be detected by the formation of small colonies of blast-like cells and are designated as stroma-adherent CFC. Cell fractionation on the basis of FLS and counting colonies on days 5, 14 and 21 revealed that there was a succession of colony formation, indicating that the stroma-adherent CFC consisted of subpopulations with different lag-phases before initiation of proliferation. Day 5, day 14 and day 21 stroma-adherent CFC were shown to have a high, intermediate and low FLS, respectively. The cells that produced GM-CFC by day 21 showed FLS properties similar to those of day 21 stroma-adherent CFC, suggesting a correlation between day 21 stroma-adherent CFC and CFC-producing cells in LTC. The CFC present on day 21 required the synergistic action of GM CSF+IL-3 + stem cell factor (SCF) for optimal proliferation. The prolonged lag phase, the low FLS and the multifactor-responsive progeny are properties similar to those reported for other early cells, and it is proposed that day 21 stroma adherent CFC represent an early hemopoietic cell type whereas day 5 stroma adherent CFC represent a more mature stage of differentiation. PMID- 8440346 TI - Bone morphology after bone marrow transplantation for Hodgkin's and non-Hodgkin's lymphoma. AB - The osteogenic consequences of bone marrow ablation followed by bone marrow transplantation for Hodgkin's and non-Hodgkin's lymphoma were examined. Pre- and post-transplantation iliac crest bone biopsies were reviewed for all patients undergoing transplantation at the Johns Hopkins Oncology Center between January 1981 and December 1989. Histomorphometric measurements included percentage of filled trabecular lacunae to estimate osteocyte viability, marrow cellularity and marrow fibrosis. A total of 37 non-Hodgkin's and 32 Hodgkin's patients had adequate biopsies for study inclusion. Twenty-seven received chemotherapy alone, while the remaining 42 had lethal total body irradiation plus chemotherapy. Twelve transplants were allogeneic. Estimated osteocyte viability was decreased for over 4 weeks after bone marrow transplantation. Continuing osteocyte dropout in the central regions of trabeculae was seen in conjunction with active new osteocyte formation along the periphery. Marrow fibrosis was significantly increased and marrow cellularity decreased. There were no major distinctions based on lymphoma type, pretransplant treatment regimen or type of bone marrow transplant. The results indicate that disruption of marrow hematopoiesis causes a diminution in osteocyte viability. Although there is an early appearance of new osteogenesis, the source of progenitor cells cannot be determined from this study. PMID- 8440347 TI - Evidence for an accessory component that increases the affinity of the erythropoietin receptor. AB - Evidence for an accessory component that can modify the affinity of the erythropoietin (Epo) receptor is presented. Dihydrofolate reductase (DHFR) deficient Chinese hamster ovary (CHO) cells were transfected with a plasmid containing the Epo receptor cDNA (derived from murine erythroleukemia cells with only low affinity receptors) and DHFR cDNA. The cells expressed both high and low affinity receptors. Upon amplification with methotrexate (MTX), only the number of low affinity receptors increased, suggesting that there was a constitutively expressed cellular component in CHO cells that can increase Epo receptor affinity. Further support for this hypothesis was provided by our finding that fusion of IW 201 cells, which have only low affinity receptors, with nontransfected CHO cells, which have no Epo receptors, resulted in high affinity binding sites for Epo. PMID- 8440349 TI - The polymerization of sickle hemoglobin in solutions and cells. AB - The polymerization of sickle hemoglobin occurs by the same mechanisms in solutions and in cells, and involves the formation of 14 stranded fibers from hemoglobin molecules which have assumed a deoxy quaternary structure. The fibers form via two types of highly concentration-dependent nucleation processes: homogeneous nucleation in solutions with hemoglobin activity above a critical activity, and heterogeneous nucleation in similarly supersaturated solutions which also contain hemoglobin polymers. The latter pathway is dominant, and creates polymer arrays called domains. The individual polymers bend, but also cross-link, and the resulting mass behaves as a solid. The concentration of polymerized hemoglobin increases exponentially unless clamped by rate limiting effects such as oxygen delivery. PMID- 8440348 TI - Membrane transport of Na and K and cell dehydration in sickle erythrocytes. AB - The cellular concentration of Hb S plays a central role in the kinetic of Hb S polymerization and cell sickling. Blood of patients with homozygous sickle cell (SS) anemia contains a variable fraction of cells which are markedly dehydrated and have increased Hb S concentration. Since a decrease in cellular Hb S concentration reduces Hb S polymerization and sickling, the study of the processes leading to sickle cell dehydration has important pathophysiological and therapeutic implications. Sickle cell dehydration is due to cellular loss of K and Cl. K loss in sickle cells can take place via either the Ca(2+)-activated K+ channel, or the K-Cl cotransport, or the combined effect of oxidative damage and deformation of the red cell membrane. Inhibitors of K transport through these pathways could be used to prevent dehydration of sickle cells in vivo, provided that they can be administered safely. PMID- 8440350 TI - Studies of a key protein in the mechanism of the excitation-contraction coupling process of frog skeletal muscle, using phenylglyoxal. AB - The excitation-contraction (E-C) coupling process in single twitch fibres from frog toe muscle was inhibited selectively by phenylglyoxal (PGO), a specific guanidyl modifying reagent. A new protein (31.5 kDa), which has PGO-binding ability and seems to play a key role in the E-C coupling process, was solubilized from transverse tubule membrane-junctional sarcoplasmic reticulum complexes (TTM JSR) of frog skeletal muscles, using 14C-PGO. The monoclonal antibody against this protein applied extracellularly inhibited the E-C coupling process of the single fibres. This protein appears to constitute the very first step of input for E-C coupling. It is considered to behave as an indispensable part of an 'electrometer' to measure membrane potentials. Therefore, the name 'electrometrin' is suggested for the new protein. PMID- 8440351 TI - A reappraisal of the hormonal regulation of larval fat body histolysis in female Drosophila melanogaster. AB - The histolysis of larval fat body cells in adult female Drosophila melanogaster was examined in wild type and mutant animals. The fat body cells of wild type (Canton-S), apterous56f homozygotes, apterous78jts homozygotes and heterozygotes, apterous4/+, ecdysoneless1 homozygotes and heterozygotes all underwent histolysis normally during the 72 h following adult eclosion. Only in the case of ap4/ap4 adults did the cells fail to histolyze normally. The fat body cells of both diapausing and non-diapausing wild type females underwent histolysis at the same rate. Attempts to demonstrate histolysis in vitro were unsuccessful, even in the presence of juvenile hormones (JHs), larval ring glands, or adult ovaries. In all strains other than the ap4 homozygotes, a significant proportion of larval fat body cells were dead at any time while the ap4/ap4 animals, almost all cells remained viable. It is postulated that fat body cell lysis following eclosion is not a JH-mediated event, but is elicited by an as yet unidentified factor(s), possibly originating in the ovary. PMID- 8440352 TI - Radioprotective effects of the immunostimulating lauroylpeptide LtriP (RP 56142). AB - The lipopeptide lauroyl-L-Ala-gamma-D-Glu-L,L-A2pm (LtriP) increased the resistance of mice to the lethal effect of gamma-ray irradiation. The radioprotective effect was dependent on the doses of LtriP and of radiation. Maximum survival was observed when the lipopeptide was injected on two successive days before irradiation. This activity seems to be related to immunostimulating functions, since the non-immunostimulating analog lauroyl-L-Ala-gamma-D-Glu-D,D A2pm-Gly, containing D,D-diaminopimelic acid, was not radioprotective. The protective activity might result from an induction of cytokines, such as IL-1, TNF and M-CSF, since LtriP induced the mRNA expression and the secretion of these immunomodulators. PMID- 8440353 TI - Cantharidin production in a blister beetle. AB - Cantharidin, a potent defensive chemical, is present in all ten life stages of the blister beetle Epicauta funebris. The first five larval stages accumulate cantharidin as they feed and grow in size. When disturbed, they exude cantharidin in a milky oral fluid, not in hemolymph which adult beetles reflexively discharge from leg joints. Two subsequent larval stages and the pupa do not feed, grow, regurgitate, or change in their defensive reserves (110 micrograms cantharidin/insect, regardless of sex). Adult beetles kept in isolation for 60-90 d exhibit a pronounced sexual dimorphism in cantharidin production: the male biosynthesizes about 17 mg of the toxin, representing 10% of his live weight, whereas the female actually loses most of her defensive reserves. But in the wild a female beetle repeatedly acquires cantharidin as copulatory gifts from her mates. PMID- 8440354 TI - Pregnanes from defensive glands of a belostomatid bug. AB - The aquatic bug Abedus herberti (Hemiptera: Belostomatidae) secretes a mixture containing four pregnanes (desoxycorticosterone (I), pregnenolone (II), progesterone (III), and 3 alpha-hydroxy-pregn-5-en-20-one (IV)) from its cephalic glands. Pregnanes had previously been characterized from the defensive glands of aquatic beetles (Dytiscidae) and shown to be deterrent to fish. It may be specifically under predation pressure from fish that A. herberti and Dytiscidae evolved their comparable defenses. PMID- 8440355 TI - High incidence of leukemic phase in follicular lymphoma in Akita, Japan: clinicopathologic, immunological and cytogenetic studies. AB - A leukemic phase occurred in 7 of 11 (64%) Japanese patients with follicular lymphoma. The clinical and hematologic features at the onset of this phase were splenomegaly, anemia, and thrombocytopenia. The lymphoma cells expressed monoclonal surface immunoglobulins with moderate to strong intensity in all 7 of the patients diagnosed as leukemic. Various B-cell associated antigens were expressed as follows: CD19 (5/6), CD20 (7/7), and CD10 (6/7). The reactivity to these markers was comparable in the lymph node and blood samples. The expression of CD38 antigen was much lower in the lymphoma cells of the blood than in those of the lymph nodes. Cytogenetic studies of the lymph nodes of follicular lymphoma in leukemic phase revealed a common chromosomal aberration, of t(14;18)(q32;q21) and +18, in 2 patients successfully analyzed. Although the follicular lymphomas in the leukemic phase in these patients in Akita, Japan, were consistent with those in the West with respect to morphology, immunology and cytogenetics, the high incidence of leukemic manifestations may be a salient feature of Japanese cases. PMID- 8440356 TI - The role of ABO matching in platelet transfusion. AB - A prospective controlled trial was performed to determine whether the use of ABO identical platelets from the start of treatment might provide higher post transfusion platelet increments, reduce the number of platelet transfusions and ultimately delay the onset of refractoriness. Forty newly diagnosed patients with haematological diseases were randomized to receive either pooled ABO-identical platelets or pooled platelets unmatched for ABO group throughout their course. The corrected platelet count increments (CCI) were calculated for the first 25 transfusions of each patient and non-immune factors present at the time of each platelet transfusion were documented. The mean CCI for the first 25 transfusions in the ABO-identical group was significantly higher (6600 +/- 7900 SD) than that achieved with ABO unmatched platelets (5200 +/- 7900; p < 0.01). The effect was most marked for the first 10 transfusions for each patient where the CCI was 64% higher in the ABO-identical group (8200 +/- 7500 vs 5000 +/- 8100; p < 0.0002). Patients given ABO-identical platelets required only about half as many transfusions in the first 30 days (10 versus 17, p < 0.05) or during the first admission (11 versus 21 p < 0.01) as patients in the ABO-unmatched group. A smaller percentage of patients in the ABO-identical group became refractory (36% vs 75% p < 0.03). The data suggest that patients requiring long-term platelet support should be transfused with ABO-identical platelets. PMID- 8440357 TI - Radioprotective potential of primitive hematopoietic precursors forming colonies in diffusion chambers in mice. AB - The purpose of this study was to determine the radioprotective ability of primitive hematopoietic precursors which form colonies in diffusion chambers in mice (CFU-D). Thirty-two lethally irradiated female ICR mice were injected with 5 to 7 male ICR mouse bone marrow-derived CFU-D colonies each. Fourteen of these mice survived over 30 days and were sacrificed at intervals up to a year. As a control, 20 lethally irradiated female ICR mice received cells from intercolony areas. All of these mice died before day 20. DNA samples obtained from hematopoietic organs and liver from 8 sacrificed mice were analyzed for the presence of CFU-D colony-derived cells. Only in 1 ICR mouse was CFU-D colony origin DNA detected by Southern analysis in all hematopoietic organs: bone marrow, spleen, thymus and lymph nodes. In 6 mice, only selected hematopoietic organs were repopulated by CFU-D colony-derived cells as judged by Southern analysis. In some of these mice, the remaining hematopoietic organs contained small CDU-D-derived cell populations which could be detected by more sensitive polymerase chain reaction (PCR). In 1 mouse, the presence of CFU-D-derived cells in all hematopoietic organs was only demonstrated by PCR. These findings suggest that lethally irradiated mice can be rescued by CFU-D-derived daughter cells. They appear to have the potential to give rise to clones containing lymphoid and myeloid cells in all hematopoietic organs, at least temporarily. Thus, it can be concluded that CFU-D represents a very primitive hematopoietic precursor cell with radioprotective capability. PMID- 8440358 TI - Lactic acidosis complicating adult T-cell leukemia: report of two cases. PMID- 8440359 TI - A granulocytosis after cutaneous contact with phenazone. PMID- 8440360 TI - The disposable teaspoon--a lethal risk to neutropenic patients. PMID- 8440361 TI - Detection of platelet antigen for antiplatelet antibodies in idiopathic thrombocytopenic purpura by flow cytometry, antigen-capture ELISA, and immunoblotting: a comparative study. AB - We compared three methods of detecting platelet antigens for antiplatelet antibodies in patients with idiopathic thrombocytopenic purpura (ITP), i.e., a microtiter well antigen-capture enzyme-linked immunosorbent assay (AC-ELISA), a platelet suspension immunofluorescence test using flow cytometry (PSIFT-FCM), and Western blotting. Using PSIFT-FCM, the reactivity of NNKY1-32, an anti glycoprotein (GP) IIb/IIIa antibody, and of NNKY5-5 (anti-GPIb) to platelets from 60 ITP patients were examined. By PSIFT-FCM, both the peak channel and the relative fluorescence value were below the mean-2SD for healthy control platelets in 15 patients when NNKY1-32 was used and in 2 patients when NNKY5-5 was used. Western blotting gave an apparent molecular weight for GPIb of 160,000, while GPIIb was 135,000 and GPIIIa was 88,000. By the AC-ELISA, 12 patients were positive for NNKY1-32 and 4 for NNKY5-5. Although NNKY1-32 binding was detected by PSIFT-FCM in 15 of the ITP patients using platelets, only 3 were positive using plasma. By AC-ELISA and Western blotting of plasma, 12 and 10 of the patients were positive for NNKY1-32 and NNKY5-5, respectively. Our results suggest that none of the three methods is good enough to stand alone and that they should be used together in the analysis of platelet antigens for antiplatelet antibodies in ITP. PMID- 8440362 TI - 9-Nitro-camptothecin delays growth of U-937 leukemia tumors in nude mice and is cytotoxic or cytostatic for human myelomonocytic leukemia lines in vitro. AB - The camptothecin derivatives 9-nitro-camptothecin (9NC) and 9-amino-camptothecin (9AC) inhibit similarly growth of HL-60, KG-1, and U-937 cells in vitro, whereas growth of THP-1 cells is inhibited by 9AC, but not by 9NC. Growth inhibition is accompanied by enlargement of cells which contain one (HL-60, THP-1) or more (KG 1, U-937) nuclei. Flow cytometry studies showed that 9NC-treated HL-60 and U-937 cells accumulate in the S and G2 phases of the cell cycle; then they die by apoptosis, with the HL-60 cells being more sensitive than U-937 cells to 9NC. In contrast, 9NC-treated KG-1 and THP-1 cells accumulate in S and G2 phases, but resist death by apoptosis. Of the cell lines tested, only U-937 cells xenografted in nude mice generated subcutaneous myeloid tumors, which exhibited a delayed growth in the presence of 9NC. Further, 9NC-treated advanced U-937 tumors regressed temporarily, indicating that U-937 cells consist of 9NC-sensitive and 9NC-resistant populations. PMID- 8440363 TI - Association between immune activation, changes of iron metabolism and anaemia in patients with HIV infection. AB - The pathogenesis of anaemia associated with human immunodeficiency virus infection is still far from being understood. It cannot be explained by direct effects of the virus on the haematopoietic system. Recent data suggest a role for immune activation. In a cross-sectional study we compared blood cell counts, haemoglobin and erythropoietin levels of 63 HIV-seropositive individuals with immune activation markers (interferon-gamma, serum and urine neopterin, and beta 2-microglobulin) and with parameters or iron metabolism (serum iron, transferrin, free iron binding capacity, ferritin). We found significant correlations between the concentrations of haemoglobin and the immune activation markers and erythropoietin concentrations. Additional significant correlations existed between the parameters of iron metabolism and haemoglobin levels, and ferritin correlated inversely with transferrin. In sum, low haemoglobin levels in patients were associated with enhanced cellular immune activation, as seen by increased interferon-gamma, neopterin and beta 2-microglobulin, and with changes of iron metabolism: low haemoglobin was associated with low transferrin and free iron binding capacity and high ferritin levels. Endogenous release of cytokines such as interferon-gamma-inhibiting erythropoiesis may be one underlying cause of anaemia in these patients. PMID- 8440364 TI - Initial versus deferred melphalan-prednisone therapy for asymptomatic multiple myeloma stage I--a randomized study. Myeloma Group of Western Sweden. AB - From October 1983 until December 1988, 50 patients with asymptomatic multiple myeloma stage I were included in a prospective randomized multi-centre study comparing melphalan-prednisone (MP) therapy started at the time of diagnosis with deferred therapy where MP was started at the time of disease progression. Twenty five patients were randomized to each group. The median time from diagnosis to start of therapy in the group with deferred therapy was 12 months. The reasons for starting therapy were increasing M-protein in 8 cases, symptomatic bone disease in 9 and anaemia in 5. In 2 cases, disease progression was complicated by vertebral fractures necessitating radiotherapy. Two patients in the group in which MP was started at the time of diagnosis developed acute leukaemia. No differences in response rate, response duration or survival were observed between the treatment groups. We conclude that in asymptomatic myeloma deferral of chemotherapy is feasible in well-informed and well-controlled patients but conveys no advantage in survival. In clinical practice the benefits of treatment deferral are to some extent outweighed by disease progression before start of treatment. PMID- 8440365 TI - Dynamics of intermediate filaments. Recent progress and unanswered questions. AB - Intermediate filaments (IFs) have always been considered as the most static and 'skeletal' cellular elements. This view is now changing: new information reveals that IFs exchange subunits at steady-state, that IF networks can be assembled de novo, and that IF proteins are subject to elaborate chemical modification and de modification during mitosis. I describe below some of the key observations which have made us realize that IFs are dynamic structures. I also discuss some of the remaining questions pertinent to the pathways of IF assembly under in vivo conditions. PMID- 8440366 TI - Avidin attachment to biotinylated amino groups of the erythrocyte membrane eliminates homologous restriction of both classical and alternative pathways of the complement. AB - Lysis of avidin-coated biotinylated sheep red blood cells (RBC) via the classical pathway of homologous (sheep) and heterologous (guinea pig) complement has been studied. The minimal surface density of avidin inducing antibody-dependent lysis via the classical pathway is smaller than that inducing antibody-independent lysis via the alternative pathway. Heterologous lysis via the classical pathway does not depend on the mode of avidin attachment: both biotinylation of membrane amino groups and insertion of biotinyl-lipid into the membrane provide the same lysis of avidin-coated RBCs by guinea pig serum in the presence of anti-avidin antibody. Avidin-free sheep RBC sensitized with hemolytic anti-RBC antibody were lysed by guinea pig, but not by sheep serum, confirming high efficiency of homologous restriction of the complement. However, avidin-coated RBCs were lysed by homologous serum in the presence of anti-avidin antibody at low surface density of avidin attached. The elimination of the homologous restriction depends on the mode of avidin attachment: biotinylation of membrane amino groups provides antibody-mediated lysis via the classical pathway of homologous complement, while insertion of biotinyl-lipid does not provide lysis. PMID- 8440367 TI - Tissue specificity of the regulation of ATP hydrolysis by isolated plant mitochondria. AB - Pea leaf mitochondria had a high ATP hydrolase activity following the collapse of the membrane potential by addition of valinomycin in state 4. In mitochondria isolated from potato tubers such ATP hydrolase activity was not observed. Pea leaf mitochondria also had a delta pH, in contrast to what was previously found for potato tuber mitochondria. This delta pH could, however, not explain the different results on ATP hydrolysis since this activity was also observed in the presence of nigericin. The results suggest a tissue-specific regulation of ATP hydrolysis in resting organs (potato tubers) as compared to active organs (leaves). PMID- 8440368 TI - The nitrogenase MoFe protein. A secondary structure prediction. AB - Surface residues, interior residues, and parsing residues, together with a secondary structure derived from these, are predicted for the MoFe nitrogenase protein in advance of a crystal structure of the protein, scheduled shortly to appear in Nature. By publishing this prediction, we test our method for predicting the conformation of proteins from patterns in the divergent evolution of homologous protein sequences in a way that places the method 'at risk'. PMID- 8440369 TI - Growth response to 4-hydroxy-L-threonine of Escherichia coli mutants blocked in vitamin B6 biosynthesis. AB - Mutants of Escherichia coli (pdx B and pdx C) which are blocked in the biosynthesis of pyridoxol (vitamin B6) showed a growth response to 4-hydroxy-L threonine. This observation constitutes the first direct evidence in support of the view that 4-hydroxy-L-threonine is implicated in the biosynthesis of vitamin B6. 1-Aminopropan-2,3-diol, the decarboxylation product of 4-hydroxy-L-threonine, does not support the growth of these mutants. Deuterium from deuterium-labelled 1 aminopropan-2,3-diol was not incorporated into pyridoxol. PMID- 8440370 TI - Downregulation of collagen synthesis in fibroblasts within three-dimensional collagen lattices involves transcriptional and posttranscriptional mechanisms. AB - Culturing human fibroblasts in a three-dimensional collagen matrix leads to a reduction of collagen I by more than 90%, both on the level of mRNA steady-state as well as protein. In order to differentiate changes in de novo transcription and posttranscriptional control, nuclear run on assays and pulse/chase experiments determining mRNA stability were used. Our results indicate that de novo transcription of the COL1A1 gene and pro-alpha 1 (I)collagen mRNA half-life are both decreased by 50% in fibroblasts grown in three-dimensional collagen lattices as compared to monolayer cultures. The extracellular matrix therefore elicits signals which are transduced from the cell surface to the inside of fibroblasts resulting in a specific reprogramming of transcriptional as well as posttranscriptional processes. PMID- 8440371 TI - Reversible inactivation and binding to mitochondria of nitrate reductase by heat shock in the yeast Hansenula anomala. AB - Heat shock from 25 degrees C to 40 degrees C of Hansenula anomala cells resulted in a rapid and reversible inactivation of the NADPH-nitrate reductase (NR) activity. The inactive enzyme retained partial activity with the non physiological co-substrates, reduced methyl viologen and reduced flavin mononucleotide. The inactive NR pelleted after centrifugation at 12,000 x g for 30 min and was associated with mitochondria. In untreated cells around 10% of the total NR is inactive and associated with mitochondria, while the active enzyme is soluble. In vitro, inactive NR could be partially dissociated from the mitochondria by incubating them at pH 11.5 or in the presence of 15 mM CHAPS. PMID- 8440372 TI - Modification of the amino acid specificity of tyrosyl-tRNA synthetase by protein engineering. AB - The amino acid specificity of Bacillus stearothermophilus tyrosyl-tRNA synthetase was studied by site-directed mutagenesis of residues close to the active site. X ray crystallographic studies of the enzyme have suggested that Asp-176 is a major determinant of amino acid specificity, as its carboxylate is observed to make a hydrogen bond with the hydroxyl group of the substrate tyrosine. Previous efforts to test the importance of Asp-176 by site-directed mutagenesis led to inactive enzymes. We have now investigated the catalytic properties of enzymes altered, not at Asp-176 itself, but instead at two amino acids, Asn-123 and Trp-126, that appear in the crystallographic structure to form hydrogen bonds with Asp-176. Mutation of Trp-126 does not affect the kinetics of activation with respect to ATP but leads to modest increases in the Km for tyrosine. Conversely, position Asn-123 mutants are strongly affected: 160-fold lower kcat and 5-fold higher Km for the Ala-123; and 17-fold decrease and 270-fold increase, respectively, of the same parameters for the Asp-123 mutation. The specificity against phenylalanine was determined from the ratios of kcat/Km for the amino acids in the pyrophosphate exchange reaction. The ratio of 1.2 x 10(5) for the wild-type enzyme decreases 4-fold on mutation of Asn-123 but increases 7-fold on the mutation of Trp-126-->Phe and 2-fold on Trp-126-->Leu. The wild-type enzyme has not reached the maximum limit of discrimination between tyrosine and phenylalanine. PMID- 8440373 TI - Association of the wasp venom peptide mastoparan with electrically neutral lipid vesicles. Salt effects on partitioning and conformational state. AB - We have measured circular dichroism signals of aqueous mastoparan and mastoparan X when titrated with electrically neutral phospholipid unilamellar vesicles. The data could be converted into association isotherms (binding curves) under various conditions of salt content. In spite of the absence of a net charge in the lipid moiety, substantial salt effects have been observed regarding the partition coefficient of the peptide and its conformation in the associated state. These results are discussed on the basis of a general thermodynamic approach for peptide association with lipid bilayers. PMID- 8440374 TI - Stereospecific assignments of the leucine methyl resonances in the 1H NMR spectrum of Lactobacillus casei dihydrofolate reductase. AB - A general method is described for the stereospecific assignment of methyl resonances in protein NMR spectra based on selective deuteration procedures. A selectively deuterated dihydrofolate reductase from L. casei was prepared by incorporating stereoselectively deuterated L-leucine, (2S,4R)[5,5,5-2H3]leucine. By comparing the COSY spectra of the dihydrofolate reductase-methotrexate complexes formed using deuterated and non-deuterated enzyme the stereospecific assignments for resonances of all 13 leucine residues were obtained by noting the absence of cross-peaks in spectra from the deuterated proteins. PMID- 8440375 TI - Interactions of calreticulin with proteins of the endoplasmic and sarcoplasmic reticulum membranes. AB - The ability of [125I]calreticulin to bind to membrane fractions isolated from different muscle and non-muscle tissues was examined by a protein overlay technique. Specific [125I]calreticulin binding proteins were detected in rat liver smooth and rough endoplasmic reticulum and Golgi, in canine pancreatic microsomes, and in rabbit skeletal muscle sarcoplasmic reticulum. These proteins were confined only to membranes that contain calreticulin; they were not found in rat liver mitochondria or cytosol. [125I]Calreticulin binds to a 50-kDa protein and a number of lower M(r) (20,000-38,000) endoplasmic reticulum membrane proteins and to 30-kDa protein in skeletal muscle sarcoplasmic reticulum. Full length calreticulin and the carboxyl-terminal region (C-domain) of the protein both competed with [125I]calreticulin for binding to the membrane proteins. Binding of [125I]calreticulin to pancreatic microsomes was also partially inhibited by the N-domain and to a lesser extent by the P-domain of the protein. We conclude that calreticulin interacts with the endoplasmic reticulum membrane proteins mainly through its carboxyl-terminal domain and that the endoplasmic and sarcoplasmic reticulum membranes may contain different calreticulin binding proteins. PMID- 8440376 TI - Probing the phalloidin binding site of actin. AB - Phallotoxins form tight complexes with filamentous actin and stabilize the polymer against shearing stress. In the present study a phalloidin derivative containing a thiol-capturing moiety was prepared and reacted with single thiol groups of monomeric muscle actin. Sites of attachment in the protein were Cys-374 next to the C-terminus and Cys-10, close to the N-terminus; the latter was recently shown to be uncovered during a slow but reversible conformational transition occurring in ADP-G-actin. Phalloidin bound to Cys-374 stabilizes filaments against shearing stress almost as effectively as free phalloidin, indicating that the phalloidin binding site cannot be far from the C-terminus of actin. Stabilization was also achieved when the phalloidin reagent was added to F actin, however, the subsequent formation of a covalent linkage with Cys-374 was not observed, most likely due to a restricted mobility of the reactants. In contrast to the efficient stabilization of filaments by phalloidin linked to Cys 374 a destabilizing effect was observed when phalloidin was attached to Cys-10. It appears that phalloidin located close to the N-terminus is unable to bind to the normal binding site in its own filament. Pronounced gelification of this actin derivative suggests that the toxin is able to mediate crosslinking with neighbouring filaments. From these results we conclude that the phalloidin binding site of actin is distant from the N-terminus, but close to the C terminus. Furthermore, the data provide evidence that binding of phalloidin reduces the mobility of the C-terminus. PMID- 8440377 TI - Presence of lipocortins I and IV, but not II and VI, in human platelets. AB - The present investigation revealed the presence of lipocortins I and IV, but not lipocortins II and VI, in human platelets. Lipocortin I was found in the Triton soluble fraction of both resting and thrombin-activated platelets and was not covalently bound to skeletal components. Without detergents, when resting platelets were lysed and fractionated in the absence of Ca2+, lipocortin I was found only in the cytosolic fraction, whereas, in the presence of Ca2+, lipocortin I was associated only with the crude particulate and not with the membrane nor the cytosolic fractions. PMID- 8440378 TI - Differential adrenergic regulation of C/EBP alpha and C/EBP beta in brown adipose tissue. AB - We investigated the regulation of the expression of two members of the C/EBP family of transcriptional activators, C/EBP alpha and C/EBP beta, in brown adipose tissue in mice. Less than one hour of cold exposure led to dramatic changes in the expression of both genes. C/EBP alpha steady-state mRNA and protein levels were drastically and rapidly reduced whereas C/EBP beta mRNA and protein levels were induced severalfold. Also norepinephrine injection affected the expression of the transcription factors. Preconfluent cells in brown fat primary cultures responded to norepinephrine with a decrease in C/EBP alpha and an increase in C/EBP beta mRNA; in confluent cells the expression of both factors was increased. Thus, C/EBP alpha and C/EBP beta gene expression is under adrenergic control both in vivo and in vitro but the type of response is directed by the degree of differentiation of the cells. PMID- 8440379 TI - Effect of pteridine derivatives on intracellular calcium concentration in human monocytic cells. AB - Pteridines are heterocyclic compounds which are synthesized and released by human monocytes/macrophages following stimulation by interferon-gamma. Their concentration in various body fluids proved to be indicative for the stimulation of the cellular immune system, and determination of pteridines has become an important diagnostic tool. We show that pteridine derivatives, namely neopterin (N), 7,8-dihydroneopterin (NH2), and 5,6,7,8-tetrahydrobiopterin (BH4) increase intracellular calcium (Cai) in human monocytic cells. Significant increases of Cai are observed at 10 nmol/l NH2, at 100 nmol/l BH4 and at 1 mol/l N, i.e. at concentrations encountered in vivo. At a concentration of 1 mumol/l, Cai is increased (from a control value of 145 +/- 7 nmol/l) to 464 +/- 62 nmol/l (NH2), 340 +/- 41 nmol/l (BH4) and 344 +/- 46 nmol/l (N), respectively. The increase of Cai depends on the presence of extracellular calcium and is likely to be due to activation of a calcium channel. We show that the absence of extracellular calcium or the addition of lanthanum ions to the extracellular fluid fully reverses the pteridine-induced increase of Cai. According to these observations, pteridines may mimic the effects of other inflammatory mediators on monocytic cells and seem to be involved in the crosstalk of immunocompetent cells. PMID- 8440380 TI - Cyclic ADP-ribose-induced Ca2+ release from rat brain microsomes. AB - Cyclic ADP-ribose (cADPR), an endogenous NAD+ metabolite in many mammalian and invertebrate tissues, is a potent mediator of calcium mobilization in sea urchin eggs. Our results show that cADPR also stimulates calcium release from rat brain microsomes, marked release occurring over the concentration range 10-250 nM. This is not inhibited by concentrations of heparin which completely abolish inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release. Ryanodine (100 microM) inhibits the cADPR response. Our results are consistent with cADPR being an endogenous messenger mediating Ca2+ release from ryanodine-sensitive pools in brain. PMID- 8440381 TI - The ligand binding domain of the nicotinic acetylcholine receptor. Immunological analysis. AB - The interaction of the acetylcholine receptor (AChR) binding site domain with specific antibodies and with alpha-bungarotoxin (alpha-BTX) has been compared. The cloned and expressed ligand binding domain of the mouse AChR alpha-subunit binds alpha-BTX, whereas the mongoose-expressed domain is not recognized by alpha BTX. On the other hand, both the mouse and mongoose domains bind to the site specific monoclonal antibody 5.5. These results demonstrate that the structural requirements for binding of alpha-BTX and mcAb 5.5, both of which interact with the AChR binding site, are distinct from each other. PMID- 8440382 TI - An enhancer unit of L-type pyruvate kinase gene is responsible for transcriptional stimulation by dietary fructose as well as glucose in transgenic mice. AB - We produced three lines of transgenic mice containing the 5' flanking region of the L-type pyruvate kinase gene from nucleotides -189 to +37, which includes an enhancer unit and TATA box as functional elements, linked to the chloramphenicol acetyltransferase gene. Since transgene expression was stimulated by both dietary fructose and glucose in a tissue-dependent manner, we suggest that this unit is responsive to both stimuli. PMID- 8440383 TI - Transport of prepro-albumin into inverted vesicles prepared from the inner membrane of rat liver mitochondria. AB - When inverted vesicles prepared from the inner membrane of rat liver mitochondria were incubated with prepro-rat serum albumin, considerable amounts of prepro albumin and pro-albumin were recovered with the inverted vesicles re-isolated by centrifugation. Pro-albumin was resistant to trypsin, but prepro-albumin was completely digested by trypsin, indicating that prepro-albumin was transported into the vesicles and concomitantly converted to pro-albumin. This transport process required ATP, but not a membrane potential. These results suggest that some export machinery for a protein having an amino acid sequence in its N terminal portion similar to the signal sequence of secretory protein exists in the inner mitochondrial membrane. PMID- 8440384 TI - 5-lipoxygenase-activating protein is an arachidonate binding protein. AB - 5-Lipoxygenase-activating protein (FLAP) is an 18-kDa integral membrane protein which is essential for cellular leukotriene (LT) synthesis, and is the target of LT biosynthesis inhibitors. However, the mechanism by which FLAP activates 5-LO has not been determined. We have expressed high levels of human FLAP in Spodoptera frugiperda (Sf9) insect cells infected with recombinant baculovirus, and used this system to demonstrate that FLAP specifically binds [125I]L-739,059, a novel photoaffinity analog of arachidonic acid. This binding is inhibited by both arachidonic acid and MK-886, an LT biosynthesis inhibitor which specifically interacts with FLAP. These studies suggest that FLAP may activate 5-LO by specifically binding arachidonic acid and transferring this substrate to the enzyme. PMID- 8440385 TI - v-Ha-Ras insertion/deletion mutants with reduced protease-inhibitory activity have no transforming activity. AB - We have purified 26 insertion/deletion mutants of v-Ha-ras oncogene products produced by Escherichia coli and investigated their protease-inhibitory activity toward papain and cathepsins B and L. Ki values for papain were relatively similar among the mutants, however, those for cathepsins B and L varied up to 10 fold. Among them, four mutants, 1-48 LIR 54-189, 1-110 LIS 112-189, 1-130 PDQ 146 189 and 1-155 LIR 166-189, showed significant reduction in the inhibitory activity toward cathepsin L and these four mutants have lost transforming activity toward NIH3T3 mouse fibroblasts. However, some other mutants also showed no transforming activity in spite of possession of the potent protease-inhibitory activity, suggesting that the protease-inhibitory activity of Ras might be necessary but not sufficient for its biological activity. PMID- 8440386 TI - Kinetic evidence that His-711 of neutral endopeptidase 24.11 is involved in stabilization of the transition state. AB - Neutral endopeptidase 24.11 (EC 3.4.24.11; NEP) is a membrane-bound Zn metalloendopeptidase with a catalytic activity and a specificity very similar to that of thermolysin, a bacterial zinc-endoprotease. NEP can be inactivated by reaction with diethylpyrocarbonate, due to the modification of a histidine residue present in the active site of the enzyme. This histidine residue was proposed to be analogous to His231 in thermolysin, which is involved in the stabilization of the tetrahedral intermediate during the transition state. Using site-directed mutagenesis of the cDNA encoding rabbit NEP, we have created two mutants of NEP where His711 was replaced by either Gln or Phe (NEP-Gln711 and NEP Phe711). Determination of kinetic parameters showed that both mutants had Km values very similar to that of the non-mutated enzyme but that their kcat values were 25-fold lower. The calculated difference in free energy needed to form the transition state complex was increased by 2.2 kcal/mol for both mutants. These observations strongly suggest that His711 is involved in the stabilization of the transition state by forming an hydrogen bond with the oxyanion of the tetrahedral intermediate. PMID- 8440387 TI - Carbohydrate structures of the cell adhesion molecule, contact site A, from Dictyostelium discoideum. AB - We determined the carbohydrate structures of contact site A from Dictyostelium discoideum. The carbohydrate moieties of contact site A were released by hydrazinolysis. Fractionation of the deacidified oligosaccharide mixture by Bio Gel P-4 column chromatography revealed that it was composed of four major oligosaccharides. Their respective structures were determined by sequential exoglycosidase digestion. It is known that contact site A consists of two kinds of carbohydrates, I and II. Taking together the previous and the present results, it was deduced that carbohydrate I comprises N-linked oligosaccharides and carbohydrate II O-linked ones. Furthermore, the relative molar contents of GalNAc and GlcNAc in reducing terminal suggested that contact site A contains 67% of N linked and 33% of O-linked oligosaccharides. PMID- 8440388 TI - Characterization of the alternative oxidase protein in the yeast Hansenula anomala. AB - The cyanide-resistant respiratory pathway is induced by respiratory inhibitors in the yeast Hansenula anomala. A monoclonal antibody against the alternative oxidase in the higher plant Sauromatum guttatum cross-reacted with a 36-kDa mitochondrial protein induced by antimycin A in H. anomala and with a protein encoded by a cDNA which was previously cloned for an antimycin A-inducible mRNA in the yeast. There was a similarity in the amino acid sequence between the cDNA encoded protein and the plant alternative oxidase protein. We propose that the 36 kDa mitochondrial protein encoded by the cDNA is a component of alternative oxidase in H. anomala. PMID- 8440389 TI - Evidence for a membrane skeleton in higher plants. A spectrin-like polypeptide co isolates with rice root plasma membranes. AB - A fraction enriched in plasma membranes was isolated from rice roots by differential centrifugation and aqueous polymer two-phase partitioning. Analysis of the fraction by SDS-PAGE showed the presence of several low mobility polypeptides (M(r) > 100 kDa). One of these polypeptides (M(r) approximately 230 kDa) was specifically recognized by polyclonal antibodies to human erythrocyte spectrin. This finding suggests that a higher plant spectrin-based membrane skeleton may be preserved and studied using high-purity plasma membrane fractions obtained by aqueous polymer two-phase partitioning. PMID- 8440390 TI - Pro-urokinase and prekallikrein are both associated with platelets. Implications for the intrinsic pathway of fibrinolysis and for therapeutic thrombolysis. AB - The contact-dependent intrinsic pathway of fibrinolysis involving factor XII, prekallikrein (PK) and pro-urokinase (pro-UK) remains poorly understood. Casein autography of washed, intact platelets revealed both PK and pro-UK. Accordingly, platelets may mediate physiological thrombolysis by this pathway since factor XIIa activates PK and kallikrein activates pro-UK. Acid washing dissociated PK but not pro-UK from platelets. Exogenous pro-UK was specifically incorporated by platelets from the ambient fluid and similarly could not be dissociated from intact platelets. Therefore, platelets may also mediate an effect from therapeutically administered pro-UK by prolonging its half-life. PMID- 8440391 TI - Purification of recombinant hepatitis delta antigen expressed in E. coli cells. AB - Recombinant DNA technology enables the massive production of recombinant hepatitis delta antigen (recHDAg) retaining immunological properties and transport functions. However, purification procedures of the recombinant delta antigen have, to date, not been described in the literature. We present a purification procedure allowing one to obtain highly purified recHDAg from bacterial cells expressing the hepatitis delta antigen. PMID- 8440392 TI - Dephosphorylation of human p34cdc2 kinase on both Thr-14 and Tyr-15 by human cdc25B phosphatase. AB - In mammalian cells, p34cdc2 kinase undergoes phosphorylation at threonine-14, tyrosine-15 and threonine-161 in the S and G2 phases of the cell cycle. At the onset of mitosis, the kinase becomes dephosphorylated at threonine-14 and tyrosine-15, resulting in activation. Cdc25 phosphatase has been shown to dephosphorylate tyrosine-15 in vitro, but whether it also does at threonine-14 remains unclear. In this study, we have found that human cdc25B phosphatase dephosphorylates both threonine-14 and tyrosine-15 but not threonine-161. PMID- 8440393 TI - Purification and characterization of the trefoil peptide human spasmolytic polypeptide (hSP) produced in yeast. AB - Recombinant human spasmolytic polypeptide (r-hSP) has been produced in relatively large amounts in Saccharomyces cerevisiae. The two intronless trefoil domains of the hSP-DNA were cloned separately by PCR from human genomic DNA, and the remaining parts of the gene synthesized. Recombinant plasmids were constructed to encode a fusion protein consisting of a hybrid leader sequence and the hSP sequence. The leader sequence serves to direct the fusion protein into the secretory pathway of the cell and to expose it to the Kex 2 processing enzyme system. The secreted r-hSP was found in a glycosylated and an non-glycosylated form. The two forms of r-hSP were purified from the yeast fermentation broth by a combination of ion-exchange chromatography and preparative HPLC. The overall yield from 8 litres of fermentation broth was 160 mg r-hSP and 219 mg glycosylated r-hSP corresponding to 50% and 34%, respectively. The structure of the r-hSP and the glycosylated r-hSP was determined by amino acid analysis and carbohydrate composition analysis as well as by peptide mapping, amino acid sequencing and mass spectrometric analysis. PMID- 8440395 TI - Generation, ethnicity, and marriage: historical patterns in the northern United States. AB - Immigration was a prominent feature of American life during the early decades of the twentieth century. About 40% of the white population was of foreign birth or parentage, and immigrants were increasingly from diverse national origins. Using data from the Public Use Microdata Sample of the 1910 U.S. Census, we examine generational and ethnic differences in marital timing. The analysis reveals a striking pattern of delayed marriage among native whites with foreign parents, but marked ethnic variation in the extent of marriage delay within the second generation. We hypothesize that locational factors, especially diverse economic opportunities, were important in shaping this marriage pattern. Separate multilevel analyses are conducted for females and for males living in urban and in rural places. Although significant effects for a variety of contextual factors are found, generational and ethnic differences in nuptial timing persist in multivariate models. PMID- 8440394 TI - Regulation of endothelin-1 action on the perfused rat liver. AB - Endothelin-1 (ET-1) was found to be a very potent stimulus for contraction and glycogenolysis in the perfused rat liver. At 1 nM it caused a dramatic increase in portal pressure of 22.1 +/- 2.7 cm water and enhanced the glucose output up to 3-fold. Extracellular Ca2+ and protein kinase C were involved in the signal transduction of ET-1. ET-1 action does not seem to be mediated by endogenous eicosanoids. The effects of ET-1 were significantly reduced in the presence of 1 microM Iloprost, a prostaglandin I2 analogue, or by 100 microM sin-1, a nitric oxide donor. In cultured hepatocytes, glycogenolysis was also stimulated by ET-1 although to an extent too small to explain the high glucose output found in the perfused liver. PMID- 8440396 TI - Use of sibling data to estimate family mortality effects in Guatemala. AB - This paper examines the potential bias in estimates of child mortality determinants produced by the questionable assumption that sibling data are independent, and estimates the unmeasured familial effects shared among siblings. The parameter estimates yielded by the multivariate hazard model are very similar to those yielded by the standard hazard model. The standard errors of the parameter estimates, however, tend to be underestimated in conventional analyses. The contribution to child mortality from the familial factors seems modest net of household socioeconomic status, at least in this Guatemalan data set. PMID- 8440397 TI - Birth interval and family effects on postneonatal mortality in Brazil. AB - In this paper random-effects logistic models are used to analyze the effects of the preceding birth interval on postneonatal mortality in Brazil, controlling for the correlation of survival outcomes between siblings. The results are compared to those obtained by using ordinary logistic regression. Family effects are found to be highly significant in the random-effects model, but the substantive conclusions of the ordinary logistic model are preserved. In particular, birth interval effects remain highly significant. PMID- 8440398 TI - Child support and welfare dynamics: evidence from Wisconsin. AB - This paper provides estimates of the effect of child support on exiting and reentering welfare for a sample of divorced women in Wisconsin. Modest amounts of child support do not have large effects on exiting welfare in this sample. The percentage of women who return to welfare is higher than has been reported previously. Receiving child support significantly decreases the likelihood of returning to welfare. PMID- 8440399 TI - The duration of breast-feeding: how is it affected by biological, sociodemographic, health sector, and food industry factors? AB - Breast-feeding duration has important effects on a wide array of demographic and maternal and infant health outcomes. This study uses a discrete-time logit hazards model to explore the relationship of biological, sociodemographic, health sector, and food industry practices on the duration of full and partial breast feeding in a sample of more than 2,600 infants from the Cebu Longitudinal Health and Nutrition Survey. Food industry and health sector practices (such as distribution of free samples of infant formula), the mother's perception of being pregnant, infant fatness, and a set of standard sociodemographic factors all affect breast-feeding duration significantly. PMID- 8440400 TI - Hutterite fecundability by age and parity: strategies for frailty modeling of event histories. AB - Effective fecundability declines with age and parity. Furthermore, women differ in their effective fecundability: some women have persistently low or high monthly chances of live-birth conception. Estimates are presented concerning the magnitude of these effects in a natural-fertility population: 406 Hutterite women in North America who had 3,206 births, largely in the 1940s and 1950s. The estimates are based on models that incorporate the effects of persistent heterogeneity and that use the full information provided by multiple-spell duration data. In addition, hazards rather than probabilities are modeled, piecewise linear hazard functions are used, and age and parity effects are decomposed systematically. These methods permit the development of more elaborate models of changing fecundability and of heterogeneity in postpartum amenorrhea. PMID- 8440401 TI - Reactivation of nonassociative memory. AB - The orienting response to an auditory stimulus, as measured by a decrease in heart rate, habituates rapidly, and at the same rate in preweanling and adult rats. Although adult rats retain this nonassociative memory for at least 7 days, preweanling rats show extremely rapid forgetting. In the preweanling, forgetting of this nonassociative memory appears to be complete after just 24 hr (Richardson & Campbell, 1991b). The results of several experiments in the present study with preweanling rats demonstrated that this type of nonassociative memory could be reactivated by presenting a fractional component of the original eliciting stimulus just prior to testing. The effectiveness of the reactivation treatment was critically dependent upon both the number of reactivating stimuli presented and the duration of those stimuli. Reactivation was also found to be stimulus specific in that presentation of an auditory stimulus qualitatively different from that used in training (white noise instead of a pure tone) did not reactivate the memory. Control groups in each experiment demonstrated that the reactivation treatment facilitated retrieval of the prior nonassociative memory and did not produce new learning. A possible process through which nonassociative memories can be reactivated is discussed. PMID- 8440402 TI - Androgen mediated effects of male fetuses on the behavior of dams late in pregnancy. AB - Two correlational studies were undertaken to explore the relationship between the sex ratio of the pups that a female Mongolian gerbil gestated and her behavior, morphology, and hormone levels late in pregnancy. In the first study, we found that the change in sex ratio between the first and second litters that a female gerbil delivered and the change in her frequency of scent marking late in her first and second pregnancies were significantly correlated. In the second study, we found significant positive correlations between both the percentage and the number of males in the litter a female delivered and (1) her plasma testosterone levels, (2) the size of her ventral gland, and (3) her frequency of scent marking, all measured late in pregnancy. Our data were entirely consistent with the hypothesis that fetal males excrete biologically significant quantities of testosterone into their dam's bloodstream and that this testosterone masculinizes both the behavior and morphology of dams late in pregnancy. PMID- 8440403 TI - A kinematic and electromyographic analysis of the development of sitting posture in infants. AB - This study was designed to describe the development of posture control in sitting in response to a natural perturbation. Seven normal infants 2 to 5 months of age were tested at two stages of independent sitting development. Trunk support was removed from infants while sitting erect and the postural responses were videotaped and EMG recorded from the upper trunk extensors, lumbar paraspinals, gluteus maximus, rectus femoris, hamstrings, and abdominals. Kinematic variables (trunk displacement, trunk velocity, trunk curvature) and an EMG variable (pattern of muscle activation) were analyzed with computer programs. Between Stages 1 and 2 of sitting development, anterior trunk displacement and velocity decreased significantly, although the trunk extension curve did not change significantly. Infants had variable muscle responses during Stage 1; however, during Stage 2 EMG analysis revealed less variability and the emergence of postural synergies. Overall, lumbar paraspinals, hamstrings, and quadriceps were the muscles most frequently active during the postural response. Each subject had a preferred synergy, with the most common synergies being a lumbar paraspinal hamstring synergy and a lumbar paraspinal-quadriceps synergy. These data provide evidence that trunk displacement and trunk velocity decrease in infants develop independent sitting posture, and these variables may be used to measure improvement in sitting control. We suggest that the control of sitting posture is related to the emergence and preferred use of the paraspinal-hamstring and paraspinal-quadriceps synergies. PMID- 8440404 TI - Stability of preference for odors after short-term exposure in young spiny mice. AB - The stability of olfactory preferences for artificial odors was studied in young spiny mouse pups (Acomys cahirinus). Subjects aged between 2 and 20 days were exposed to the odor of either cinnamon or cumin for 1.5 hr. The durability of preferences for the familiar versus novel odor was subsequently monitored in a three-choice preference test. The results suggest the existence of a sensitive phase for learning odor characteristics, through simple exposure, between Days 2 and 18 of the pups' postnatal life. The sensitive phase proved not to be an "on off" process, but the strongest effect of exposure to odors took place at about Days 4 and 6. However, the duration of preference for exposed odors was dependent on later experience with the odors during retests. The results point to an unusual plasticity in rapid learning of odors through simple exposure in precocial young spiny mice. PMID- 8440405 TI - Emeritus professors can, assistant professors mustn't. PMID- 8440406 TI - Electromagnetic field interactions with biological systems. AB - This is a report on Symposia organized by the International Society for Bioelectricity and presented at the 1992 FASEB Meeting. The presentations summarized here were intended to provide a sampling of new and fruitful lines of research. The theme topics for the Symposia were cancer, neural function, cell signaling, pineal gland function, and immune system interactions. Living organisms are complex electrochemical systems that evolved over billions of years in a world with a relatively simple weak magnetic field and with few electromagnetic energy emitters. As is characteristic of living organisms, they interacted with and adapted to this environment of electric and magnetic fields. In recent years there has been a massive introduction of equipment that emits electromagnetic fields in an enormous range of new frequencies, modulations, and intensities. As living organisms have only recently found themselves immersed in this new and virtually ubiquitous environment, they have not had the opportunity to adapt to it. This gives us, as biologists, the opportunity to use these electromagnetic fields as probes to study the functioning of living systems. This is a significant opportunity, as new approaches to studying living systems so often provide the means to make great leaps in science. In recent years, a diversity of biologists have carried out experiments using electromagnetic fields to study the function of living cells and systems. This approach is now becoming quite fruitful and is yielding data that are advancing our knowledge in diverse areas of biology. PMID- 8440407 TI - Aminopeptidases: structure and function. AB - Aminopeptidases catalyze the cleavage of amino acids from the amino terminus of protein or peptide substrates. They are widely distributed throughout the animal and plant kingdoms and are found in many subcellular organelles, in cytoplasm, and as membrane components. Several aminopeptidases perform essential cellular functions. Many, but not all, of these peptidases are zinc metalloenzymes and are inhibited by the transition-state analog bestatin. Some are monomeric, and others are assemblies of relatively high mass (50 kDa) subunits. cDNA sequences are available for several aminopeptidases, and a 3-dimensional structure is available for the bovine lens enzyme. Crystallographic, electron micrographic, NMR, and photoaffinity labeling studies indicate that lens leucine aminopeptidase protomers are bilobal and that bestatin and substrates are bound in an active site, which is found in the larger lobe on each protomer. Zn2+ is involved in substrate liganding in most aminopeptidases. There is no evidence of an acyl enzyme intermediate in hydrolysis. Amino acid sequences determined directly or deduced from cDNAs indicate some amino acid sequence homologies in organisms as diverse as Escherichia coli and mammals, particularly in catalytically important residues or in residues involved in metal ion binding. PMID- 8440408 TI - von Willebrand factor. AB - von Willebrand factor is a multimeric glycoprotein essential for the normal arrest of bleeding after tissue injury (hemostasis). The molecule is present in blood, both in plasma and inside platelets, as well as in endothelial cells and the subendothelial matrix of the vessel wall. Through multiple functional domains, von Willebrand factor mediates the attachment of platelets to exposed tissues, where discontinuity of the vascular endothelium occurs, and the subsequent platelet aggregation leading to the formation of platelet thrombi. The crucial role of von Willebrand factor in platelet function is particularly apparent when hemodynamic conditions create blood flow with high shear stress, as in capillaries under physiologic conditions or in stenosed and partially occluded arteries in disease states. The involvement of von Willebrand factor in the processes that lead to acute thrombosis has attracted considerable interest on the molecular and functional biology of the protein. Indeed, understanding the mechanisms and structural bases for von Willebrand factor function may result in new and effective approaches to anti-thrombotic intervention. PMID- 8440409 TI - Cellular metabolism and activation of retinoids: roles of cellular retinoid binding proteins. AB - Vitamin A and related molecules--the retinoids--play essential roles in vision, growth, reproduction, and cellular differentiation beginning in early development. Retinoic acid, a key regulatory retinoid formed intracellularly through the oxidation of retinol, functions as ligand for a family of nuclear retinoic acid receptors that regulate transcription from target genes. Metabolic events are critical to maintaining physiological concentrations of retinoic acid. In the cytoplasm, retinol, retinaldehyde, and retinoic acid are associated with retinoid-binding proteins, most of which are approximately 15-kDa proteins belonging to the fatty acid-binding protein/cellular retinol-binding protein family. The ligand binding properties and molecular features of these proteins have been well characterized. Recent experiments have highlighted the importance of the cellular retinoid-binding proteins in controlling the concentration of free retinoids and in directing protein-bound retinoids to key enzymes responsible for their metabolism. For example, the cellular retinol-binding protein, CRBP, has been implicated in retinol uptake, retinol esterification, mobilization of retinyl esters, and the initial oxidation of retinol to retinaldehyde. The ligands bound to other retinoid-binding proteins have also been shown to be available for enzymatic transformation. The new knowledge of the various ways these cytoplasmic proteins buffer the concentration of ligand, control their distribution, and determine their metabolism by specific enzymes is contributing to an improved understanding of the physiological control of retinoid action. PMID- 8440410 TI - New insights on mammalian phospholipase A2(s); comparison of arachidonoyl selective and -nonselective enzymes. AB - With the recent discoveries of novel forms of phospholipases A2 (PLA2s),2 new schemes for the roles of various PLA2s in lipid metabolism must be considered. The type II 14-kDa PLA2 isolated from human synovial fluid or platelet has many of the biochemical characteristics of the homologous snake venom and mammalian pancreatic PLA2s. It appears to function both as a cell-associated enzyme and extracellularly, where its expression and/or release is regulated by a variety of mediators such as cytokines or growth factors. The mammalian 85-kDa PLA2 purified from monocytic cells or platelets has no sequence homology to the 14-kDa PLA2 and exhibits biochemically different characteristics. It translocates from cytosol to particulate cell fractions in the presence of submicromolar levels of Ca2+ and has a substrate preference for sn-2-arachidonoyl-containing phospholipids. The cellular function and relative importance of these two enzymes in lipid metabolism remain to be determined. In this review, the biochemistry, localization, function, and regulation of these two distinct mammalian Ca(2+) dependent PLA2 are compared. PMID- 8440411 TI - Measurement of nitric oxide in biological models. AB - Nitric oxide (NO) is a small, gaseous, paramagnetic radical with a high affinity for interaction with ferrous hemoproteins such as soluble guanylate cyclase and hemoglobin. Interest in NO measurement increased exponentially with the discovery that NO or a related compound is the endothelium-derived relaxing factor (EDRF). In addition to being a potent endogenous vasodilator, NO has a role in inflammation, thrombosis, immunity, and neurotransmission. Measurement of NO is important as many of its effects (e.g., vasodilatation, inhibition of platelet aggregation) are similar to those of other substances produced by the endothelium, such as prostacyclin. NO is formed in small amounts in vivo and is rapidly destroyed by interaction with oxygen, making measurement difficult. A computerized search of the past five year's literature found NO measurements reported in fewer than 50 of 955 articles dealing with EDRF. Inhibitors of NO synthesis such as the arginine analogs or agents that inactivate NO, such as reduced hemoglobin, are commonly used as specific probes for NO, in vivo and in vitro; however, none of the NO inhibitors is completely specific. The most widely used assays use one of three strategies to detect NO: 1) NO is "trapped" by nitroso compounds, or reduced hemoglobin, forming a stable adduct that is detected by electron paramagnetic resonance (EPR) (detection threshold approximately 1 nmol); 2) NO oxidizes reduced hemoglobin to methemoglobin, which is detected by spectrophotometry (detection threshold approximately 1 nmol); 3) NO interacts with ozone producing light, "chemiluminescence" (detection threshold approximately 20 pmol). These assays can be performed to exclusively detect NO, or by adding acid and reducing agents to the sample, can measure NO and related oxides of nitrogen such as nitrite. Several new amperometric microelectrode assays offer the potential to measure smaller amounts of NO (10(-20) M), permitting NO measurement in intact issues and from single cells. This review describes the pharmacology and toxicology of NO and reviews the major techniques for measuring NO in biological models. PMID- 8440412 TI - Overexpression of mitochondrial manganese superoxide dismutase promotes the survival of tumor cells exposed to interleukin-1, tumor necrosis factor, selected anticancer drugs, and ionizing radiation. AB - Interleukin-1 (IL-1) and tumor necrosis factor (TNF) selectively induce mitochondrial manganese superoxide dismutase (MnSOD) production in various cell types. We have evaluated the capacity of tumor cells that overexpress MnSOD to recover from the cytostatic and cytotoxic effects of cytokines (IL-1 and TNF), chemotherapeutic agents, and ionizing irradiation. Clones of human melanoma cell line, A375, which overexpressed MnSOD after sense MnSOD cDNA transfection, showed increased recovery from treatment with cytostatic and cytotoxic doses of IL-1 alpha and TNF alpha, whereas clones of A375 cells that were transfected with anti sense MnSOD cDNA recovered less well than normal cells from IL-1 alpha and TNF alpha. In addition, Chinese hamster ovary (CHO) cells transfected with sense MnSOD cDNA showed increased survival after treatment with doxorubicin, mitomycin C, and gamma (gamma) radiation in vitro. It is hypothesized that mitochondrial MnSOD, by scavenging oxygen radicals induced by cytokines, some cytotoxic drugs, and ionizing radiation, is protective and promotes the survival of cells from the lethal effects of these treatments. PMID- 8440413 TI - A 1-hour pulse with IL-1 beta induces formation of nitric oxide and inhibits insulin secretion by rat islets of Langerhans: evidence for a tyrosine kinase signaling mechanism. AB - Nitric oxide has been implicated as the effector molecule that mediates interleukin-1 beta (IL-1 beta)-induced inhibition of glucose-stimulated insulin secretion by rat islets. Brief exposures of islets (1 h) to IL-1 beta have been shown to inhibit glucose-stimulated insulin secretion at 8 or 18 h after removal of this cytokine. The purpose of this investigation was to determine if brief exposures of islets to IL-1 beta are sufficient to induce the formation of nitric oxide and to examine the signaling process associated with IL-1 beta-induced expression of nitric oxide synthase. We demonstrate that a 1-h pretreatment of islets with IL-1 beta followed by an 8-h incubation in the absence of this cytokine results in inhibition of glucose-stimulated insulin secretion (50%), which is completely prevented by pretreatment of islets with the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (NMMA). The production of nitric oxide by islets under these pulse conditions is demonstrated by IL-1 beta-induced nitrite and electron paramagnetic resonance-detectable iron-nitrosyl complex formation, both of which are prevented by NMMA. IL-1 beta initiates a signal transduction process resulting in the expression of nitric oxide synthase. The signaling process appears to require the activation of a tyrosine kinase, since the tyrosine kinase inhibitor genistein prevents both IL-1 beta-induced inhibition of insulin secretion by islets and formation of nitric oxide by the insulinoma cell line RINm5F. These results show that short exposures of islets to IL-1 beta are sufficient to induce the formation of nitric oxide resulting in inhibition of glucose-stimulated insulin secretion and that a tyrosine kinase may participate in the early signaling events required for IL-1 beta to induce the expression of nitric oxide synthase. PMID- 8440414 TI - Novel Drosophila laminin A chain reveals structural relationships between laminin subunits. AB - Laminins are trimeric glycoproteins composed of A, B1, and B2 chains that play important roles in cell adhesion and differentiation and in the assembly of basement membranes. There is evidence that multiple independent gene products can be used to supply the A, B1, and B2-like chains, thereby generating diverse laminin molecules. The set of A chain-like polypeptides are the most divergent. The amino-terminal portion of each chain, called the short arm, is composed of alternating cysteine-rich and globular domains. The amino-terminal two-thirds of the newly characterized Drosophila laminin A chain appears to encode a novel structure, but the analysis presented here shows that substantial portions of its amino acid sequence are related to sequences found in other A, B1, and B2 chains. A portion of the Drosophila A chain is composed of sequences like those found in B2 chains. These sequences parallel a portion of the vertebrate A chains, suggesting a structure for a shared ancestral A chain. However, unlike vertebrate A chains, the Drosophila A chain also contains sequences typical of B1 chains, suggesting that its gene must have arisen by recombination of segments from different primordial laminin genes. PMID- 8440415 TI - From antigen to antibody. PMID- 8440416 TI - An animal model of longitudinal ulcers in the small intestine induced by intracolonically administered indomethacin in rats. AB - The ulcerogenic effect of intracolonically administered indomethacin was evaluated in rats. Conventionally fed rats aged from 5 to 10 weeks were treated by 8, 16, 24, or 32 mg/kg of intracolonic indomethacin for two days, and any damage to the stomach, small intestine and the colon was investigated. Longitudinal ulcers and scattered small ulcers were found in the small intestine at all doses of indomethacin, and the length of the longitudinal ulcers increase dose-dependently, but this was unrelated to the body weight of the rats. The cecum was frequently affected by irregularly shaped ulcers, and the incidence increased as the dose of indomethacin increased. The colon, other than the cecum, was not involved macroscopically. In contrast, the stomach was affected by only large doses of indomethacin (24 or 32 mg/kg), and the size of gastric ulcers increased according to the body weight of the rats. These findings suggest that intracolonic indomethacin in relatively young rats causes ulcers predominantly in the small intestine and the cecum, which are the frequent site of involvement of human Crohn's disease, and that this animal model may be suitable for investigation of the pathophysiology of inflammatory bowel disease. PMID- 8440417 TI - A case of appendiceal mucocele showing massive mucous production with concomitant colonic cancer. AB - A 58-year-old male patient presented with abnormal discharge of 200 ml transparent fecal mucus. Irregular protuberance of the ascending colon into the adjacent ileocecal region was observed by colonofiberscopy, and a cystic lesion in the ileocecal region was suggested by computerized axial tomography. Pale yellowish semitransparent jellied substances were observed exudating from the site of ileocecal resection. The diagnosis established was moderately differentiated colonic adenocarcinoma and a mucocele of the appendix. The mucus discharge disappeared after resection. Biochemical analysis of the mucus suggested the mucocele as a source of the discharged mucus. We report an extremely rare case of mucocele of the appendix that may be related to the cause of mucous stool. PMID- 8440418 TI - Reversibility of hepatopulmonary syndrome evidenced by serial pulmonary perfusion scan. AB - A patient with liver cirrhosis who exhibited marked hypoxemia is presented. An abnormal dilatation of intrapulmonary capillaries was evidenced by perfusion lung scan, contrast-enhanced echocardiography, and histological examinations of lungs. Serial perfusion lung scan disclosed that the radioisotope uptake by extrapulmonary organs was significantly increased and uptake by both lungs was significantly decreased during the state of severer hypoxemia. Shunt quantification method revealed that intrapulmonary right-to-left shunt ratio also paralleled the extent of hypoxemia. The pathophysiology of hepatopulmonary syndrome appeared to involve a reversible intrapulmonary vascular dilatation. The perfusion lung scan could semiquantitate the severity of intrapulmonary vascular dilatation and could offer the efficient method to follow their progress. PMID- 8440419 TI - Characteristic features of alcoholic liver disease in Japan: a review. AB - The characteristics of alcoholic liver disease (ALD) in Japanese patients were reviewed and compared with those in Western countries. From the study in Japanese cases, it became clear that alcoholic fibrosis and chronic hepatitis induced by alcohol were types of ALD other than the traditional 3 types. Liver injury in Japanese cases was clearly milder than that in American cases. In American cases, the injury may be fully developed, because of greater alcohol and fat intake. This may be one reason why the two above types of ALD have not been mentioned in the literature of Western countries. In Japanese patients, hepatitis C virus (HCV) infection is not related to alcoholic fibrosis and alcoholic hepatitis. On the other hand, the prevalence of HCV markers was high in chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) patients. Alcoholic hepatitis and chronic hepatitis are the high risk groups for the development of cirrhosis and the chronic hepatitis group is at high risk for the development of HCC. Although the risk is low in alcoholic fibrosis, some patients also develop cirrhosis. About half of the cases of cirrhosis may develop from alcoholic hepatitis and alcoholic fibrosis, and the remaining half cases may develop from chronic hepatitis. Over 80% of HCC cases may develop from chronic hepatitis in Japan. Chronic alcoholism enhanced the development of HCV-related HCC. Recent increase of HCC in alcoholic cirrhosis in Japan may be related to the increase of alcohol consumption, the increase of blood transfusions, and longer survival of cirrhosis patients. PMID- 8440420 TI - Interleukin 6 production by peripheral blood mononuclear cells in patients with chronic hepatitis B virus infection and primary biliary cirrhosis. AB - IL-6 production by peripheral blood mononuclear cells (PBMC) was studied in patients with chronic hepatitis B virus (HBV) infection and primary biliary cirrhosis (PBC) using the ELISA method. Spontaneous production of IL-6 was significantly increased in patients with HBeAg+ chronic hepatitis (CH). The cultures stimulated with lipopolysaccharide and lectin-free interleukin-2 (IL-2) showed enhanced IL-6 production both in controls and all patient groups compared with culture without any stimulation. IL-6 production in response to IL-2 was higher in patients with HBeAg+ CH and PBC than in controls. In PBMC with increased IL-6 production, monocyte function was increased in patients with HBeAg+ CH and PBC, while B cells from PBC showed elevated response to Staphylococcus aureus Cowan 1. IL-6 production in the presence of HBeAg was greater in anti-HBe+ patients than in HBeAg+ ones. These results suggest that IL 6 response is involved in the immune response in patients with chronic liver disease. PMID- 8440421 TI - Clinical significance of low or negative titer of antibody to hepatitis B core antigen during the course of chronic hepatitis B virus infection in adolescents. AB - Antibody to hepatitis B core antigen (anti-HBc) was measured by radioimmunoassay in 127 asymptomatic hepatitis B surface antigen (HBsAg) carriers (ASC; mean age 19) who had normal serum alanine aminotransferase (ALT) levels and 16 patients with chronic hepatitis B (CH; 19). All 16 CH patients, who were positive for hepatitis B e antigen (HBeAg) and 5 ASC cases who were negative for both HBeAg and its antibody (anti-HBe), had high anti-HBc titers. Anti-HBc titers in 27 (56.3%) of the 48 HBeAg-positive ASC and 18 (24.3%) of the 74 anti-HBe-positive ASC were relatively low. Two of the ASC were HBeAg-positive/anti-HBc-negative. In a follow-up study of the 19 HBeAg-positive ASC with low or negative anti-HBc titers, 5 had abnormal serum ALT levels and increased anti-HBc titers. In contrast, in the other 14 of these subjects, serum ALT levels remained normal and the low anti-HBc titers remained unchanged and/or decreased. The serological profile of HBsAg-positive/low or negative anti-HBc titer and increased anti-HBc titer with abnormal serum ALT levels are not necessarily exceptional in HBeAg positive adolescent ASC. It is suggested that anti-HBc is associated with the liver damage that occurs before adolescence in chronic hepatitis B virus infection. PMID- 8440422 TI - Glutathione S-transferases in primary cultured rat hepatocytes. AB - The present study is aimed to elucidate the changes in glutathione S-transferase (GST) activity and GST subunit components in primary cultured rat hepatocytes. Enzyme activity was measured with 1-chloro-2,4-dinitrobenzene as cosubstrate. The activity decreased at 48 hr, and subsequently increased and returned to levels initially observed at 12 hr by 120 hr. Phenobarbital caused an induction of GST activity in culture at 72 and 168 hr. Immunocytochemical studies were performed using a peroxidase-anti-peroxidase technique with three polyclonal antibodies: anti-Ya, Yb1 and Yp. With anti-Ya, hepatocytes were persistently positive up to 144 hr in cell culture. With anti-Yb1, hepatocytes were positive at 24 hr, though positivity then gradually decreased. On the other hand, with anti-Yp, cells were almost negative at 48 hr and became obviously positive at 96 hr. Immunoelectron microscopy with anti-Yb1 using the avidin-biotin ferritin method revealed ferritin particles in the ribosomes on endoplasmic reticulum as well as in the free cytoplasmic space. In conclusion, the GST subunit components are in a state of dynamic change in cultured rat hepatocytes, and overall time-dependent increase in the total activity of the enzyme can be accounted for by increased expression of the Yp subunit. Finally, the intracellular localization of Yb1 subunit was clarified in the present report. PMID- 8440423 TI - Localization of a new enteric non-A, non-B [HEV] virus in target organ liver. AB - Thirteen Macaca mulatta monkeys were used for transmission of enteric non-A, non B hepatitis virus (HEV) by the portal vein (PV) route. All these animals developed changes which are found in self-limiting acute viral hepatitis e.g. rise in liver enzymes, the presence of HEV specific viral particles in the stool and histological changes in the liver from 21 to 45 days after HEV inoculation. All the animals recovered completely as reflected by normalization of liver enzymes, and regenerative changes in the liver. The present report highlights the ultrastructural changes in the livers of these experimental monkeys. The histopathological changes included infiltration of lymphocytes and polymorphonucleocytes around the necrotic area, swelling of mitochondria, dilation of smooth endoplasmic reticulum (ER), and presence of 27-34 nm virus particles during the acute phase of the disease. In comparison, 9 control monkeys did not show any such histological changes. PMID- 8440424 TI - Elevated serum thymidine kinase activity in patients with acute viral hepatitis. AB - To evaluate the clinical applications of serum thymidine kinase (TK) activity, we compared the results obtained with this parameter with those of other liver function tests in 27 patients with acute viral hepatitis and 16 normal controls. In those in the acute stage, the serum TK activity increased significantly to 55.5 +/- 66.5 U/L. There was no significant correlation between serum TK activity and findings for serum albumin, bilirubin, alkaline phosphatase or r-glutamyl transpeptidase. However, it did correlate significantly well with the serum activity of aspartate aminotransferase (AST) (r = 0.621, P < 0.01), alanine aminotransferase (ALT) (r = 0.551, P < 0.01), and lactate dehydrogenase (LDH) (r = 0.620, P < 0.01). Serum TK activity reached higher than 70 U/L in 8 of 11 patients with hepatitis A; however, no patients with the other types of hepatitis reached such a high level. During the recovery stage, the serum TK activity decreased significantly to 5.9 +/- 1.7 U/L (P < 0.01), and did not correlate with AST, ALT, LDH or other conventional liver function parameters. The data suggest that an elevation of serum TK in patients with acute viral hepatitis results from hepatocellular damage. A marked elevation of serum TK activity may thus provide a marker for acute hepatitis A infection. PMID- 8440425 TI - The therapeutic effect of a new synthetic protease inhibitor (E-3123) on hemodynamic changes during experimental acute pancreatitis in dogs. AB - The therapeutic effect of a new synthetic protease inhibitor on hemodynamic changes was studied in experimental acute pancreatitis. Pancreatitis was induced by the injection of autologous bile mixed with trypsin into the main pancreatic duct after ligating the accessory duct. Plasma beta-endorphin concentrations and cardiovascular function were measured. Seventeen dogs (control group) were given 10 ml/kg/hr of lactate Ringer's solution intravenously 1 hr before the induction of pancreatitis and throughout the experiment. Seven dogs (the low protease inhibitor group) were given an intravenous bolus injection of 0.4 mg/kg of a new synthetic protease inhibitor, E-3123 (4-(2-succiminido-ethylthio)4 geranidinobenzoate methanesulfate) 30 min after the induction of pancreatitis and then a continuous intravenous infusion at 3 micrograms/kg/min throughout the experiment. Seven dogs (the high protease inhibitor group) received an intravenous bolus injection of 3 mg/kg and a continuous intravenous infusion at 50 micrograms/kg/min of E-3123 according to the same method as in the low protease inhibitor group. The mortality rate during the experiment was 41% (7/17) in the control group, 28.5% (2/7) in the high protease inhibitor group and 0% in the low protease inhibitor group. The increase in the plasma beta-endorphin levels in the control group was statistically significant. When E-3123 was given 30 min after the induction of pancreatitis, the increase in the plasma beta endorphin levels in the high protease inhibitor group was also found to be increased statistically significant, compared with preinduction levels, but the increase was statistically significantly lower than that in the control group. Plasma beta-endorphin levels in the low protease inhibitor group, however, did not increase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8440426 TI - A case of spontaneous intramural hematoma of the esophagus. AB - The authors experienced a case of spontaneous intramural hematoma of the esophagus (SIHE). This 44-year-old Japanese woman was admitted to our hospital because of chest pain accompanied by minimal hematemesis. Endoscopy revealed an elevated intraluminal bleeding bulge. Barium esophagograms showed a smooth and giant elevated intraluminal lesion. CT and MRI also revealed thickening of the esophageal wall. Fasting and intravenous hyperalimentation were prescribed on admission. The conditions improved and she became asymptomatic on the fifth day of hospitalization. Subsequent examinations by esophagography and endoscopy showed that the elevated lesion had disappeared and that the inflamed mucosal lesion had improved. The prognosis of cases of SIHE is excellent under conservative therapy, but close follow-up care is necessary. PMID- 8440427 TI - A case report of resected primary duodenal carcinoma associated with early gastric cancer and cumulative results at 21 institutions in Japan. AB - A case of primary duodenal carcinoma simultaneously associated with an early gastric cancer is reported. A 72-year-old woman complaining of appetite loss and nausea was admitted in June 1988. Endoscopic examination showed an ulcerative lesion in the angle of the stomach and a Borrmann type 2 tumor in the bulb of the duodenum. Both lesions were revealed to be adenocarcinomas by histological examination of obtained biopsy specimens. Synchronous carcinoma was diagnosed and pancreatoduodenectomy and lymph node dissection were performed. The primary tumor of the duodenum was histologically a moderately differentiated adenocarcinoma, and the gastric cancer was a tumor limited to the mucosa. Metastasis was recognized in a regional lymph node (No. 14A). There has been no recurrence during the 4-year postoperative follow-up period. This result suggests that pancreatoduodenectomy with systematic regional lymph node dissection can greatly contribute to prolonging the survival of patients with advanced duodenal cancer. This case is very rare, in that curative operation was performed for a primary duodenal carcinoma simultaneously associated with an early gastric cancer. PMID- 8440428 TI - The transplantation of gastrointestinal organs. AB - Over a period of 33 years, it has become possible to successfully transplant individual intra-abdominal viscera or combinations of these organs. The consequences have been, first, new information about the metabolic interrelations that the visceral organs have in disease or health; second, the addition of several procedures to the treatment armamentarium of gastrointestinal diseases; and third, a more profound understanding of the means by which all whole organ grafts are accepted. PMID- 8440429 TI - Design of a microwave system for endoscopy: an experimental study of energy, tissue contact, and hemostatic efficacy. AB - BACKGROUND: A microwave generator and delivery system for endoscopic use was built. Using a 650-W, 2450-MHz magnetron, 0-160 W were generated from the tip of a 180-cm flexible coaxial cable (2.1 mm diameter). METHODS: Three methods of achieving hemostasis with microwaves were identified studying standard bleeding canine ulcers: (1) interstitial method: inserting the coaxial tip into the tissue and heating slowly until bleeding stopped; (2) contact method: tip held in contact, light pressure applied; (3) noncontact method: microwave-induced sparking (dielectric breakdown) with tip held 1 mm from tissue. RESULTS: Studies of optimal energy levels for hemostasis showed that high power (70 W) noncontact methods required significantly less energy to stop bleeding than contact or interstitial methods. The noncontact method was more effective than the contact method, stopping 20 of 20 bleeding ulcers vs. 10 of 20 (P < 0.001) and was more rapidly effective causing less tissue damage (P < 0.05) than the interstitial method. CONCLUSIONS: In a randomized comparison using a non-contact method, microwave coagulation was superior (P < 0.001) to a polidocanol 1% + adrenaline 1:10,000 injection and control treatment stopping 40 of 40 vs. 0 of 20 and 0 of 20 standard bleeding ulcers. Microwaves stopped bleeding from 10 of 10 severed mesenteric vessels, whereas injection was ineffective (0 of 10, P < 0.001). Microwaves look promising for hemostasis at flexible endoscopy. PMID- 8440430 TI - Rat intestinal M cells contain acidic endosomal-lysosomal compartments and express class II major histocompatibility complex determinants. AB - BACKGROUND: It is generally believed that M cells do not modify the antigens they transport from the intestinal lumen to underlying immunocompetent cells because it has been reported that M cells contain few elements of the lysosomal system. METHODS: We used specific cytochemical and immunocytochemical probes to examine whether M cells in jejunal Peyer's patches of adult rats contain the requisite intracellular components to process and potentially present endocytosed antigens. RESULTS: M cells contained acid phosphatase-enriched prelysosomelike and lysosomelike structures. A basic congener of dinitrophenol, which concentrates in acidic cell compartments, is localized following its instillation into Peyer's patch-containing ligated jejunal loops to the endosomal-lysosomal system of M cells. Prelysosomelike and lysosomelike structures in ultrathin cryosections of M cells reacted with polyclonal antibody to a membrane glycoprotein (lgp120) enriched in prelysosomes and lysosomes. Using monoclonal antibody OX6 as a probe, M cells expressed the major histocompatibility complex (MHC) class II determinant, Ia, on the basolateral plasma membrane and in organelles with structural features of endosomes, prelysosomes, and lysosomes. Expression was enhanced by pretreatment with interferon gamma. CONCLUSIONS: M cells possess acidic endosomal and acid phosphatase-containing prelysosomal and lysosomal compartments and express MHC class II determinants. Hence, M cells may have the capacity to process and present endocytosed antigens to adjacent intraepithelial T lymphocytes. PMID- 8440431 TI - Zaldaride maleate, an intestinal calmodulin inhibitor, in the therapy of travelers' diarrhea. AB - BACKGROUND: The therapeutic value of zaldaride maleate (Zm), an intestinal calmodulin inhibitor, was examined in patients with travelers' diarrhea, known to be caused by enterotoxigenic Escherichia coli (ETEC) and other bacterial agents. METHODS: One hundred seventy-six American students acquiring diarrhea in Mexico during the summer of 1991 were given Zm in doses of 5 mg, 10 mg, or 20 mg, or a matching placebo, four times a day for 48 hours. RESULTS: The duration of diarrhea was reduced by 53% in the group given the 20-mg Zm dose (overall P < 0.01). Curative antibiotics were required post-treatment only in the placebo and 5-mg Zm groups (P < 0.01). The number of unformed stools passed during 0-48 hours of therapy with the highest Zm dose was reduced compared with placebo by 36% for all subjects (P < 0.05), by 39% for ETEC diarrhea (NS), by 45% for those with any bacterial agents (NS), and by 38% for those without an identifiable bacterial agent (NS). CONCLUSIONS: The fact that a calmodulin inhibitor decreases the severity and duration of travelers' diarrhea has therapeutic implications and suggests that calmodulin and intracellular calcium may serve as mediators of diarrhea in bacterial enteric infection. PMID- 8440432 TI - Psychological stress-induced accelerated colonic transit in rats involves hypothalamic corticotropin-releasing factor. AB - BACKGROUND: Brain corticotropin-releasing factor (CRF) is involved in stress induced accelerated colonic transit. Brain sites of action of CRF to stimulate colonic transit were investigated in conscious fed rats. METHODS: Bilateral guide cannulae were chronically implanted into the paraventricular nucleus of the hypothalamus (PVN) or central amygdala for peptide microinjection and a catheter into the proximal colon to measure colonic transit. RESULTS: CRF (0.6 nmol/rat) injected into the PVN reduced colonic transit time by 84% and stimulated fecal pellet output 20-fold, whereas CRF injected into sites outside of the PVN or the central amygdala had no effect. CRF stimulatory action was prevented by chlorisondamine, and atropine methyl nitrate but not by bretylium. The stress of avoiding water by standing on a small cube reduced colonic transit time by 75% and increased fecal output by 7-fold. Bilateral microinjection of CRF antagonist, alpha-helical-CRF, into the PVN abolished the colonic response to stress. The CRF antagonist had no effect on basal colonic transit time in nonstressed rats. CONCLUSIONS: Psychological stress-induced stimulation of colonic motor function in fed rats involves CRF pathways in the PVN. PMID- 8440433 TI - Distinct associations of HLA class II genes with inflammatory bowel disease. AB - BACKGROUND: There are relatively few studies of HLA class II association either with Crohn's disease (CD) or ulcerative colitis (UC). The few available association studies have been carried out by serological techniques, and the results from these studies are inconclusive. METHODS: The association between HLA class II genes was studied using molecular genotyping in combination with allele specific oligonucleotide hybridization by polymerase chain reactions. RESULTS: In UC (n = 74), we observed a positive association with the HLA DR2 allele (P = 0.008) and negative associations with the DR4 (P = 0.018) and DRw6 (P = 0.028) when compared with ethnically matched controls (n = 77). No associations were observed with any DQ alleles. In contrast, in CD (n = 95) we observed a positive association with the combination of DR1 and DQw5 alleles (P = 0.021). Furthermore, stratifying DR1 and DQw5 alleles indicated that neither allele was independently associated with CD, suggesting that the association was with the haplotype rather than either of the alleles individually. A suballele of DQw5, DQB1*0501, contributed this haplotypic association (P = 0.012). CONCLUSIONS: DR and DQ molecules firmly separate UC and CD on genetic grounds, suggesting that the contribution of the HLA class II genes to the disease susceptibility is quite different for the two disorders. PMID- 8440434 TI - Localization of intestinal interleukin 1 activity and protein and gene expression to lamina propria cells. AB - BACKGROUND: Interleukin 1 (IL-1) is a key mediator of bowel inflammation, but there is limited knowledge about the amount and site of production of this cytokine in the gastrointestinal tract under physiological or pathological conditions. METHODS: Epithelial and lamina propria mononuclear cells were isolated from control, and Crohn's disease- and ulcerative colitis-involved mucosa to investigate the capacity of these cells to generate IL-1 bioactivity, IL-1 alpha and IL-1 beta immunoreactivity, and gene expression. RESULTS: Control lamina propria mononuclear cells produced substantial amounts of IL-1 alpha and IL-1 beta, which increased dramatically when inflammatory bowel disease cells were used. Epithelial cells from control, Crohn's disease, and ulcerative colitis intestine displayed no IL-1 bioactivity or immunoreactivity. Lamina propria mononuclear cells contained moderate to large quantities of IL-1 alpha and IL-1 beta messenger RNA (mRNA), respectively, whereas epithelial cells had none. The absence of IL-1 transcripts in epithelial cells was selective, because mRNA for HLA-DR antigens was present in control and inflammatory bowel disease cells. CONCLUSIONS: In normal and inflamed human intestine there is a distinct compartmentalization of IL-1, as mononuclear but not epithelial cells generate this cytokine. The high levels of IL-1 in inflammatory bowel disease may explain several of its local and systemic manifestations, and blockade by specific antagonists could have important therapeutic effects. PMID- 8440435 TI - Immunohistochemical localization of transforming growth factor alpha in the developing rat colon. AB - BACKGROUND: Transforming growth factor alpha (TGF-alpha) is a 50-amino acid polypeptide that has been related to cell proliferation and differentiation. METHODS: Proximal and distal colon from fetal, newborn, and adult rats were studied by immunohistochemical techniques using a monoclonal antibody against human and rat TGF-alpha. RESULTS: Immunoreactive TGF-alpha (IR-TGF-alpha) first appeared in distal colon at 18 days of gestation when the proximal colon remained negative. At all ages studied, the staining for TGF-alpha at the base of the crypts in the distal colon showed a supranuclear pattern. At 22 days of gestation and until 9 days of postnatal development, the proximal colon is negative for TGF alpha. From day 10 to 24 of postnatal development, IR TGF-alpha cells with a cytoplasmic staining were confined to the lower half of the villi. Afterwards, cells at the crypts showed supranuclear staining and cells in the surface epithelium a cytoplasmic reaction. CONCLUSIONS: Age- and region-dependent expression of TGF-alpha in the rat colon suggests a functional role for TGF-alpha in the establishment and maintenance of proliferation and differentiation during development. PMID- 8440436 TI - Cell kinetics of mucosal atrophy in rat stomach induced by long-term administration of ammonia. AB - BACKGROUND: Helicobacter pylori produces ammonia in the stomach from urea. The present study was undertaken to clarify whether ammonia has an etiological role in H. pylori-associated gastric mucosal atrophy. METHODS: Ammonia at 0.01% was administered as drinking water for 8 weeks and mucosal cell migration rate and cell proliferation were investigated in rat stomach. RESULTS: Long-term administration of 0.01% ammonia for 4-8 weeks decreased mucosal thickness in the antrum but not in the body. Acceleration of cell migration preceded the occurrence of mucosal atrophy. Labeling indices in both antral and body mucosa significantly increased in all ammonia-treated groups, compared with those of the control group. In the antrum, the proliferative zone was significantly enlarged as mucosal atrophy developed, whereas, in body mucosa, enlargement of the proliferative zone occurred despite the absence of mucosal atrophy. CONCLUSION: Ammonia at 0.01% accelerates epithelial migration, especially in the antrum, leading to mucosal atrophy. Acceleration of epithelial proliferation occurs during the development of mucosal atrophy. PMID- 8440437 TI - Reducing sulfur compounds of the colon impair colonocyte nutrition: implications for ulcerative colitis. AB - BACKGROUND: Mercaptides (sodium hydrogen sulfide and sodium methanethiol) and mercapto-fatty acid (sodium mercaptoacetate) are reducing agents that help to maintain anaerobic conditions in the colonic lumen. The metabolic effect of these agents on n-butyrate and glucose oxidation in human colonocytes is unknown. METHODS: Isolated human colonocytes were prepared from 31 colectomy specimens, and generation of oxidative metabolites from [1-14C]n-butyrate and [6-14C]glucose was measured in the presence and absence of reducing agents. Injury to cells was judged by diminished production of metabolites. RESULTS: The injurious action of mercaptides at all sites of the colon was of the order of sodium hydrogen sulfide > methanethiol > mercaptoacetate. Significant inhibition of n-butyrate (< 0.005) but not glucose oxidation was observed with sodium hydrogen sulfide in the ascending colon, splenic flexure, and rectosigmoid region. Hydrogen sulfide more significantly inhibited fatty acid oxidation in the rectosigmoid than in the ascending colon (P < 0.02). CONCLUSIONS: Metabolic effects of sodium hydrogen sulfide on butyrate oxidation along the length of the colon closely mirror metabolic abnormalities observed in active ulcerative colitis, and the increased production of sulfide in ulcerative colitis suggests that the action of mercaptides may be involved in the genesis of ulcerative colitis. PMID- 8440438 TI - Indomethacin-induced renal dysfunction in patients with well-compensated cirrhosis. AB - BACKGROUND: Patients with cirrhosis and ascites are especially sensitive to the adverse renal effects of indomethacin-induced inhibition of prostaglandin synthesis. The aim of this study was to determine whether indomethacin affects renal function in patients with well-compensated cirrhosis. METHODS: Clearance techniques were used to assess renal hemodynamics and sodium and water homeostasis. RESULTS: The oral administration of 50 mg of indomethacin to well compensated patients with alcoholic cirrhosis was followed by a significant decrease in glomerular filtration rate (GFR) and effective renal plasma flow because of a preferential increase in afferent arteriolar tone. Indomethacin was both antidiuretic and antinatriuretic due principally to decreased free water clearance and increased proximal tubular reabsorption of sodium. The acute changes in renal function were not sustained. Patients with a high basal GFR were particularly sensitive to the adverse renal effects of indomethacin. CONCLUSIONS: This study indicates that in patients with well-compensated cirrhosis renal prostaglandins are functionally active and may contribute to the pathogenesis of glomerular hyperfiltration. Nonsteroidal anti-inflammatory drugs should be used with caution in all patients with cirrhosis. PMID- 8440439 TI - Glomerular hyperfiltration in patients with well-compensated alcoholic cirrhosis. AB - BACKGROUND: Peripheral and splanchnic arteriolar tone is often decreased in patients with cirrhosis. The responsible circulating vasodilator(s) would be expected to also lower renal vascular resistance. To examine this possibility we have undertaken a hemodynamic study of the renal circulation in patients with stable, well characterized, compensated cirrhosis and in healthy controls of similar age and sex. METHODS: Clearance techniques were used to assess splanchnic and renal hemodynamics and hepatocellular function. RESULTS: Renal vascular resistance was significantly reduced in the cirrhotic patients (P = 0.048) and was accompanied by a significant (P = 0.014) and proportional (r = -0.45; P = 0.016) increase in glomerular filtration rate. The hepatic extraction of indocyanine green, a measure of functional intrahepatic portasystemic shunts, was the only independent predictor of glomerular filtration rate (r = -0.65; P = 0.002). CONCLUSIONS: The results support the hypothesis that, in patients with cirrhosis, the presence of portasystemic shunts results in an increased delivery of endogenous vasodilator(s) into the systemic circulation where their principal action on the renal circulation is to preferentially decrease afferent arteriolar tone. The resultant glomerular hyperfiltration may contribute to the pathogenesis of cirrhotic glomerulosclerosis. PMID- 8440440 TI - Gut macromolecular permeability in pancreatitis correlates with severity of disease in rats. AB - BACKGROUND: Increased intestinal macromolecular permeability could allow absorption of substances from the bowel into the systemic circulation and contribute to multiple organ system failure. METHODS: Mild, intermediate, and severe grades of pancreatitis were induced in rats using intravenous caerulein and intraductal glycodeoxycholic acid. [14C]polyethylene glycol (molecular weight, 3350 daltons; 1.1 microCi/142 mg) was instilled into the distal duodenum. At 24 hours, the animals were killed, ascitic fluid was collected for trypsinogen activation peptide measurement, and pancreatic specimens were collected and scored for based on the degree of necrosis, inflammation, and hemorrhage. RESULTS: Gut permeability to polyethylene glycol 3350 (PEG 3350) was increased in animals with early experimental pancreatitis (5.4% +/- 1.2%, n = 20) when compared with control animals (1.8% +/- 0.2%; n = 6) (P = 0.0005). Furthermore, intestinal macromolecular permeability to PEG 3350 correlated with severity of disease as predicted by the method of induction of pancreatitis (P = 0.0003), the histological findings (P = 0.0002), and total ascitic trypsinogen activation peptides content (P = 0.029). CONCLUSIONS: Increased gut permeability in experimental pancreatitis can be correlated with pancreatitis severity. PMID- 8440441 TI - Exacerbation of lichen planus during interferon alfa-2a therapy for chronic active hepatitis C. AB - A 66-year-old man was treated for chronic active hepatitis C with 3 MU of recombinant interferon alfa-2a three times weekly. Nine months before interferon therapy, a mild lichen planus had been diagnosed, which exacerbated within 4 weeks of treatment to a generalized erosive lichen planus. After 8 weeks, interferon therapy was stopped because local measures did not improve skin lesions. Otherwise, the patient tolerated interferon therapy well, and the initially 20-fold elevated aminotransferase levels returned to normal. Four weeks after discontinuation of interferon therapy, nearly all mucosal and skin lesions had disappeared. But 8 weeks after the discontinuation, aminotransferase levels again rose to 10 times the normal range. Treating physicians should know that a preexisting lichen planus will potentially exacerbate as a side effect of interferon alfa-2a therapy of a chronic hepatitis. However, because this is the first report on this association, further observations are needed to decide the clinical relevance. PMID- 8440442 TI - Generalized juvenile polyposis with mixed pattern and gastric cancer. AB - Generalized gastrointestinal juvenile polyposis is a rare form of diffuse polyposis in which cancer infrequently develops. A clinical case is described in which gastric polyps showed a variety of histological features, including both in situ and invasive adenocarcinoma. Many mixed lesions were observed, confirming a morphological sequence already documented in colorectal tumorigenesis but still undefined in gastric tumors. The patient seems strongly predisposed to gastric cancer, presumably on a genetic basis, because he developed a malignancy in a hyperplastic juvenile polyp, usually not considered a precancerous lesion. There is no doubt that cases like this may be important for accurate genetic evaluation and biological characterization. PMID- 8440443 TI - Microwaves and the gut. PMID- 8440444 TI - Another challenge to the Opie myth. PMID- 8440445 TI - The kidneys in hepatic cirrhosis: victims of portal-systemic venous shunting (portal-systemic nephropathy) PMID- 8440446 TI - Appendectomy--will the laparoscope reign? PMID- 8440447 TI - Immunonutrition? PMID- 8440448 TI - Leiomyosarcoma: not all gastric malignancies have a dismal prognosis. PMID- 8440449 TI - Promises, promises: ursodeoxycholic acid for primary sclerosing cholangitis. PMID- 8440450 TI - Variable age of onset in hereditary nonpolyposis colorectal cancer: clinical implications. PMID- 8440451 TI - Intestinal involvement in sarcoidosis. PMID- 8440452 TI - Alkaline esophageal reflux--a misnomer. PMID- 8440453 TI - [Diagnostic results and their clinical interpretation--or: what you never wanted to know about diagnosis]. AB - Diagnostic test results become only relevant if clinically interpreted. A key issue in clinical interpretation is the predictive value which, however, in daily practice and even in medical literature, is frequently misunderstood, as if the predictive value would be about the same as sensitivity. Sensitivity and specificity of a test only together with the prevalence of the target disease allow estimation of the predictive values. This correlation will be exemplified with the diagnosis of chorioamnionitis measuring C-reactive protein: The predictive value is not constant, but depends on prevalence. Prevalence, however, changes with clinical situation, therefore similar test results must be clinically interpreted very differently. Finally, considering these correlations, decision analysis using the "threshold model" shows how to develop a rational, quantitative approach to the selection and interpretation of diagnostic tests. Although more and more studies on decision analysis in diagnostics are published, up to now, there is little response in day-to-day practice. This situation should be changed for the sake of our patients. PMID- 8440454 TI - [Follow-up of tumor markers in evaluating the effectiveness of chemo- or hormone therapy in metastatic breast cancer]. AB - We compared the course of the tumour markers CEA and CA 15-3 with the clinical course of 62 patients with metastasising breast cancer. The patients were treated by an aggressive chemotherapy (FAC-regimen) or high-dose hormonal therapy (1000 mg MPA/day). The markers were determined after a well-defined schema. In patients treated with aggressive chemotherapy, the markers were determined 4, 8 and 12 hours as well as 7 days after each course. In patients treated with hormonal therapy, the markers were determined weekly from the first to 12th week as well as 4, 8 and 12th week after onset of therapy. The course of the tumour markers was compared with the results of the radiological and clinical staging three months after beginning of therapy. For patients treated with aggressive chemotherapy CEA withdrawn 4 hours after the first and second cycle resulted in medium predictive values of 88% for marker increase and 93% for marker decrease. In comparison, the predictive values of CA 15-3 were 81% for marker increase and 71% for marker decrease. Both markers obtained better results when withdrawn four hours after therapy compared to values withdrawn 7 days after therapy. In high dose hormonal therapy, the determination of markers collected four weeks after onset of therapy is sufficient for predicting the clinical course. The medium predictive values of CEA after 4 and 8 weeks amount to 83% for marker increase and 87% for marker decrease. In comparison, the predictive values of CA 15-3 are 95% vs. 85%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8440455 TI - [The value of reoperation in the treatment of ovarian cancer]. AB - Recurrent ovarian cancer is still a significant problem despite intensive primary therapy, consisting of radical surgery and subsequent chemotherapy. The primary reason for consequent follow up investigations and immediate start of second-line therapy in cases of recurrence is based on the fact, that patients with relapse more than 12 months after primary therapy have a mean survival of 105 weeks after diagnosis. The value of surgical treatment is controversially discussed in the literature. Several authors argue, that there is no definitive prolongation of survival. Between January 1984 and July 1990, 285 patients presented themselves at our hospital with recurrence or progression of ovarian cancer. 72 of these patients had surgical treatment and those patients are part of the investigation. The mean survival of the patients (n = 18), which were operated with no remaining tumour, was 166 weeks. The average survival time of the 22 women with up to 2 cm remaining tumour was 108 weeks. The average survival time of the 32 patients with more than 2 cm after surgery was 72 weeks. One important criterion for the achievable tumour-free situation after surgery was the distinction between primary progression and relapse, where relapse was defined as recurrence more than 12 months after primary treatment. 29% of the patients with relapse could be operated tumour-free, a situation which could be achieved only in one of 13 patients (8%) with primary progression of the disease. Surgery in recurrent ovarian cancer is only indicated in patients with relapse more than 12 months after primary surgery. Tumour-free patients have significant benefit from the surgical procedure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8440456 TI - [Prevention of human birth trauma I. Computer-assisted simulation of delivery using magnetic resonance tomography and finite element analysis]. AB - Imaging procedures suitable for diagnosis of cephalopelvic disproportion, such as radiological pelvimetry, computer- or magnetic resonance imaging (MRI) fail to reflect the dynamics of delivery, including deformations of the birth channel as well as of foetal structures. In order to validate findings of imaging procedures in this respect, a method has been developed to perform dynamic, biomechanical postprocessing of the static information obtained from MRI. Using a specially developed software MRI pixel, matrices of the maternal pelvis and the foetal head were colour-coded and--according to the principle of equal density--line data were created. After sectional attribution of the resulting polygones, a three dimensional mesh of so called Finite Elements (FE) was created, which can then be used for deformation analysis. The foetal head was then moved through the birth channel by means of computed simulation. This allows not only ongoing deformations to be visualised, but also resulting forces can be calculated at any time of the delivery process for any point of the anatomical model. Furthermore, these calculations can be performed assuming various conditions such as different cephalopelvic dimensions and various labour forces or biomechanical properties of the tissues involved. This paper aims at presenting the method and its mode of working by means of one example of a computed birth simulation. PMID- 8440457 TI - [Discordant growth in twin pregnancy--value of Doppler ultrasound]. AB - A 4 MHz continuous-wave Doppler device was used to study uterine and umbilical arterial wave forms in 91 pairs of twins between 18th and 40th week of gestation. Biometry and cord localisation were effected by real-time ultrasound. The results of 182 Doppler flow examinations showed that umbilical flow velocimetry may prove relevant for early identification of twin pregnancies with discordant growth. Depending on the interval between examination and delivery, sensitivity and specificity values between 44% and 66%, and 66% and 73%, respectively, were obtained. A high resistance index in umbilical arteries was indicative of intrauterine growth retardation, at a specificity of 69% and a sensitivity of 44%. For uteroplacental as well as foetoplacental flow velocity waveform assessment, singleton reference values may be used, whereas, by reason of its low sensitivity, Doppler flow velocimetry does not lend itself as a primary diagnostic tool for intrauterine growth retardation. It can signal pathologic blood flow profiles, which are often associated with added risks, such as pregnancy-induced hypertension, foetal acidosis and stillbirth and can contribute to early detection of twin pregnancies that require close clinical and cardiotocographic surveillance. PMID- 8440458 TI - [The value of Doppler ultrasound studies within the scope of obstetric management in unexpected findings in the cardiotocograph]. AB - In a study of 30 cases with moderate or serious foetal heart rate alterations, we examined the influence of Doppler ultrasound on our obstetrical management. Normal results of Doppler umbilical artery flow velocity waveform analysis would allow us in 22 of 24 cases, to continue the pregnancy under usual control. Only in two cases with moderate foetal heart rate alterations, absence of labour and a normal Doppler result, Caesarean section was necessary because of foetal distress. A pathological Doppler result was found in six cases with intrauterine growth retardation. These risks were not known prior to the patients hospitalisation. Surprisingly, we found only moderate foetal heart rate alterations in these cases. Without any further control of the foetal heart rate, we decided to perform Caesarean section immediately after the Doppler investigation. We are of the opinion, that Doppler ultrasound could be very useful in obstetrical management to decide, if the pregnancy must be ended or could possibly be continued in cases of premature birth. PMID- 8440459 TI - [Survey of the availability and utilization of Doppler ultrasound in German speaking areas]. AB - The study was performed about the spread and usage of Doppler ultrasound measurements. Standardised questionnaires were sent to the obstetrical departments of 253 universities and teaching hospitals. 59% of the hospitals answered the questions. At the university departments, the method was used regularly. On the average twice the number of patients have been examined compared to the teaching hospitals. The obstetricians in the university departments were more experienced in safety determinations and quality control. Most of the university departments used their own norm curves. When measuring the resistance in the favoured vessels umbilical artery, middle cerebral artery and arcuate arteries, the resistance index (RI) was preferred to the pulsatility Index (PI) in both kinds of hospitals. The most severe pathological findings, zero and reverse flow, occurred with an incidence of more than 2% only in hospitals with less than 500 patients a year, indicating false positive results due to inexperienced physicians. Relevant software is not commercially available; therefore documentation and evaluation of the data was done manually in most of the departments. There are different opinions about the use of Doppler ultrasound as a screening test. However, Doppler ultrasound is seen as a valuable method for diagnosis of hypoxia especially in cases of intrauterine growth retardation and pregnancy-induced hypertension. In the year 2000 the method might be widely used in nearly every small hospital and even in offices. This development without adequate training of the obstetricians might result in a high incidence of false positive results. PMID- 8440460 TI - [Tuberculous mastitis--a rare differential diagnosis of non-puerperal mastitis]. AB - Tuberculosis in a case of non-puerperal mastitis is a rare clinical finding. A special case of a 28-year old Thai patient was diagnosed and successfully treated with an antituberculous chemotherapy. The most important diagnostic procedure was the microbiological and histological investigation to enable the diagnosis to be made. Surgical therapy was not necessary. PMID- 8440461 TI - [Pregnancy and laryngeal cancer]. AB - Although cancer during pregnancy is not a common clinical problem, its occurrence is associated with much anxiety distress for patient and physician alike. Such concern arises from the fact, that two lives are involved, and that decisions regarding evaluation of treatment of the mother may have direct consequences for the foetus. We discuss treatment and prognosis of laryngeal cancer during pregnancy of a 33 year old patient. PMID- 8440462 TI - Conformation of Escherichia coli outer membrane protein OmpA produced in Bacillus subtilis: influence of lipopolysaccharide. AB - The conformation of the outer membrane protein OmpA of Escherichia coli produced in Bacillus subtilis and solubilized in Sarkosyl was studied by measuring its ability to bind OmpA-specific phage K3 and to inhibit F-mediated conjugation. The partially purified protein was inactive in both of these assays. Refolding of the protein in the presence of lipopolysaccharide resulted in preparations with full phage-binding and conjugation-inhibiting capacity, indicating the formation of surface-exposed loops of OmpA of native conformation. The finding is of importance for the potential use of outer membrane proteins of Gram-negative bacteria as vaccines. PMID- 8440463 TI - Effects of immobilization on growth, morphology, and DNA content of the ciliated protozoon Tetrahymena thermophila. AB - Morphological and physiological properties of Tetrahymena thermophila immobilized by encapsulation in calcium-alginate hollow spheres were found to be substantially different from those of suspended cells. Immobilized T. thermophila reached lengths of 70-100 microns, whereas the average cell of suspension cultures was about 40 microns long. Suspended cells appeared typically pear shaped while immobilized cells developed a proboscis-like anterior end. Contrary to suspended T. thermophila, encapsulated cells were functionally deficient in phagocytosis although developing an oral apparatus. The diameter of the macronucleus of immobilized cells was about two times larger than the macronucleus of suspended cells and contained twice as much DNA, while the DNA content of the micronucleus remained unchanged. High cell density fermentations of suspended cells indicated that the alterations observed in immobilized cells were not due to close physical contacts between the cells. PMID- 8440464 TI - Environmental strains of Enterococcus faecium with inducible high-level resistance to glycopeptides. AB - High-level resistance to glycopeptides in Enterococcus faecium is associated with an inducible 39-kDa cytoplasmic membrane protein. The present paper shows that such glycopeptide-resistant E. faecium strains can not only be isolated in a definite clinical setting but also from waste water of sewage treatment plants. Nearer characterization of these and of clinical isolates by resistance pattern, biotyping, and genotyping (DNA-fingerprinting with pulsed-field gel electrophoresis) has shown that different glycopeptide-resistant E. faecium strains have been isolated from clinical sources and from waste water. PMID- 8440465 TI - Inhibition of Bordetella pertussis filamentous hemagglutinin-mediated cell adherence with monoclonal antibodies. AB - Filamentous hemagglutinin (FHA), a 220-kDa protein located on the surface of Bordetella pertussis, is one of the major cell adhesins of this bacterium. We have produced three hybridoma cell lines that express monoclonal antibodies (mAbs) against FHA: X3C, X3E and X4B. The anti-FHA mAbs X3C and X3E reacted with 220-kDa and 98-kDa FHA protein bands on Western blots. The mAb X4B, which reacted with FHA in ELISA, did not bind to FHA in a Western blot assay. All three mAbs seemed to be directed to the same epitope or to epitopes in close proximity as suggested by competition ELISAs. All three mAbs were able to inhibit the adherence of Chinese hamster ovary cells to purified FHA, and they could also inhibit the FHA-mediated agglutination of goose red blood cells. The attachment of B. pertussis to epithelial cell monolayers was inhibited by the mAb X3C. These antibodies are very useful probes to identify the presence of FHA in bordetellae species and in clinical reagents such as pertussis vaccines, and to characterize the functional domains of this important bacterial adhesin. PMID- 8440466 TI - Influence of drying on the survival of anaerobic fungi in rumen digesta and faeces of cattle. AB - Tolerance of anaerobic fungi in the faeces and rumen digesta of cattle to drying in air at approx. 20 degrees C or 39 degrees C was investigated. Anaerobic fungi were able to survive in dried faeces, but no significant survival was observed in digesta collected from five different regions of the rumen. Anaerobic fungi in faeces also survived when samples were dried in the presence of rumen digesta. When dried in the presence of sterile faeces, however, anaerobic fungi in rumen digesta failed to survive the drying process. The most plausible explanation for these results is that, during passage from the rumen to the rectum, anaerobic fungi undergo a transition to a dormant form resistant to air-drying. PMID- 8440467 TI - The role of conserved tryptophan residues in the interaction of a bacterial cellulose binding domain with its ligand. AB - The five conserved tryptophan residues in the cellulose binding domain of xylanase A from Pseudomonas fluorescens subsp. cellulosa were replaced with alanine and phenylalanine. The mutated domains were fused to mature alkaline phosphatase, and the capacity of the hybrid proteins to bind cellulose was assessed. Alanine substitution of the tryptophan residues, in general, resulted in a significant decrease in the capacity of the cellulose binding domains to bind cellulose. Mutant domains containing phenylalanine substitution retained some affinity for cellulose. The C-terminal proximal tryptophan did not play an important role in ligand binding, while Trp13, Trp34 and Trp38 were essential for the cellulose binding domain to retain cellulose binding capacity. Data presented in this study suggest major differences in the mechanism of cellulose attachment between Pseudomonas and Cellulomonas cellulose binding domains. PMID- 8440468 TI - A 16S rRNA-based DNA probe and PCR method specific for Listeria ivanovii. AB - A 16S rRNA-based DNA probe and polymerase chain reaction (PCR) method was developed for identification and rapid detection of Listeria ivanovii. The probe (R-1) is 5'-GTAGTGACGCATGTCATCAC-3' corresponding to positions 185-204 in the L. ivanovii 16S rRNA sequence. DNA hybridization results indicated that R-1 probe only reacted with L. ivanovii, and not with six other species of Listeria or other bacteria tested. The PCR method using R-1 and a reverse primer, R-2, was positive with all eight strains of L. ivanovii tested but was negative with six other species of Listeria, including nine strains of L. monocytogenes, and 20 other taxonomically related bacteria tested. In our PCR method, starting with whole bacterial cells, only 3 h were required for the PCR assay and 1 h for electrophoresis without any additional time for DNA isolation and DNA hybridization. This PCR method detected as few as 4 cells of L. ivanovii in pure cultures and 4-40 cells of L. ivanovii in inoculated and diluted mouse feed, blood, or faeces samples. PMID- 8440469 TI - Location of fructose in lipopolysaccharide isolated from 01 Vibrio cholerae NIH 41R. AB - Fructose, a rarely occurring sugar constituent of Gram-negative bacterial lipopolysaccharides (LPS), is distributed ubiquitously in LPS of 01 Vibrio cholerae so far examined, but its location in LPS has not hitherto been elucidated. It was found that hydrazinolysis of LPS successfully affords a derivative retaining virtually all the fructose of intact LPS, but no ester-bound phosphate. Structural analysis carried out on the LPS derivative prepared by the hydrazinolysis of R-type LPS isolated from a rough mutant strain (NIH 41R) of 01 V. cholerae NIH 41 (Ogawa) revealed that the fructose is present as a non reducing terminal residue bound to position C-6 of a glucose residue in the core region. This finding is considered to exclude the possibility that, in the LPS of 01 V. cholerae, the fructose is present in the region of the inner core in place of 2-keto-3-deoxyoctonate. PMID- 8440470 TI - Topology, structure and evolution of two families of proteins involved in antibiotic and antiseptic resistance in eukaryotes and prokaryotes--an analysis. AB - Analysis of deduced amino acid sequences has demonstrated that the sequences of eukaryotic and prokaryotic proteins mediating resistance to antibiotics and antiseptics are highly related. Hydropathy analysis and alignment of conserved motifs revealed that these proteins can be divided into two separate families with either 12 or 14 transmembrane segments (TMS). Conserved motifs have been identified which are either characteristic for each family or conserved in both families. The conservation of these motifs suggested that they may be essential for the function of these proteins. Phylogenetic and structural analysis revealed that the two families may have evolved from a common ancestor with six TMS. PMID- 8440471 TI - Cloning of the lysA gene from Mycobacterium tuberculosis. AB - The lysA and proC genes of Mycobacterium tuberculosis were cloned by screening of a recombinant lambda gt11 M. tuberculosis DNA library for phages able to complement lysA and proC Escherichia coli mutants. The lysA gene encodes diaminopimelic acid decarboxylase which catalyzes the conversion of diaminopimelic acid (DAP) to lysine. The lysA gene from M. tuberculosis encodes a 44-kDa protein, as determined by maxicell experiments. The nucleotide sequence of the structural gene was established. The deduced amino acid sequence was found to exhibit significant homology (from 55% to 73% similarity, and from 27% to 53% identity) to DAP decarboxylase sequences from other bacterial species. PMID- 8440472 TI - Isolation of a yeast essential gene, COF1, that encodes a homologue of mammalian cofilin, a low-M(r) actin-binding and depolymerizing protein. AB - We have cloned a Saccharomyces cerevisiae gene (COF1) encoding a low-M(r) actin binding protein of 143 amino acid (aa) residues (yeast cofilin; Cof); its aa sequence is 35% identical to porcine Cof. The yeast recombinant Cof produced in Escherichia coli exhibited in vitro activities on actin filaments similar to those of mammalian and avian Cof. Gene disruption and tetrad analysis showed that gene COF1 is essential for yeast cell growth. Expression of the cDNA of porcine Cof or destrin (Des), the latter a Cof-related protein, complemented the cof1 null allele in yeast cells. PMID- 8440473 TI - Isolation and characterization of a beta-tubulin-encoding gene from Colletotrichum gloeosporioides f. sp. aeschynomene. AB - Colletotrichum gloeosporioides f. sp. aeschynomene (C.g.a.) is a fungal pathogen of legumes and is used as a commercial mycoherbicide for rice and soybeans. As an initial study to potentially improve the utility of this fungus and develop a gene transfer system, a beta-tubulin (beta Tub)-encoding gene (TUB1) was isolated, cloned and sequenced. The coding sequence and deduced amino acid sequence of the C.g.a. TUB1 gene was highly homologous to the TUB1 gene of Colletotrichum graminicola. Southern hybridizations, using the C.g.a. TUB1 and C. graminicola TUB2 genes as probes, suggest that C.g.a. contains two TUB genes. Variation in both the restriction pattern and the number of TUB genes present in different formae specialis of C. gloeosporioides was evident. These observations are relevant for assessing relationships among formae specialis of C. gloeosporioides. PMID- 8440474 TI - A tandemly repeated sequence from the Plasmopara halstedii genome. AB - A 747-bp tandem repeat element from the genome of the fungus Plasmopara halstedii, the causal agent of downy mildew of sunflower, was cloned and analyzed. The clone can be used as a probe to distinguish races of the pathogen. Sequence analysis of a copy of this element revealed the presence of 103 direct repeats of 6 bp or greater and two potential ORFs. This tandemly repeated element consists of four subunits that may have evolved as a result of several unequal crossing-over events. PMID- 8440475 TI - A new luciferase promoter insertion vector for the analysis of weak transcriptional activities. AB - A new luciferase-encoding expression vector was generated by inserting the strong transcription termination signal from the mouse c-mos oncogene upstream from a multiple cloning site. This construct significantly reduced background transcription in NIH3T3 cells and has proven useful in the study of a weak promoter from the murine growth-arrest-specific gene gas-1. PMID- 8440476 TI - The sequence of Saccharomyces cerevisiae cloning vector pCS19 allowing direct selection for DNA inserts. AB - The complete nucleotide sequence of plasmid pCS19 has been determined. This centromeric Saccharomyces cerevisiae cloning vector was designed for the construction of gene libraries, since it allows direct selection for DNA inserts. PMID- 8440477 TI - The vanB gene of vancomycin-resistant Enterococcus faecalis V583 is structurally related to genes encoding D-Ala:D-Ala ligases and glycopeptide-resistance proteins VanA and VanC. AB - We report the cloning and sequencing of a 632-bp amplified fragment internal to the vanB gene of vancomycin-resistant (VmR) Enterococcus (En.) faecalis V583. The DNA fragment hybridized to VmR strains of En. faecium and En. faecalis, but not to their susceptible derivatives. PMID- 8440478 TI - Characterization of polygalacturonases. AB - Lei et al. [Gene 117 (1992) 119-124] recently published the nucleotide sequence of the peh gene of Erwinia carotovora subsp. carotovora (Ecc) and a characterization of its product endopolygalacturonase (Peh). The gene appears highly similar to previously described peh sequences of Ecc [Hinton et al., Mol. Microbiol. 4 (1990) 1029-1036; Saarilahti et al., Mol. Microbiol. 4 (1990) 1037 1044] which were not cited in the article. Ecc carries a single peh gene whose product, Peh, is here shown to share similarity with the two Pehs characterized thus far and a Peh-like protein of eukaryotic origin at the amino acid (aa) sequence level. Additionally, a highly conserved region within their C-terminal domains was found to share local similarity with two 13-aa segments of an otherwise distinct exo-poly-alpha-D-galacturonosidase (exo-Peh), suggesting that these segments might be required for enzyme activity in both Peh and exo-Peh. PMID- 8440479 TI - Escherichia coli host strains SURE and SRB fail to preserve a palindrome cloned in lambda phage: improved alternate host strains. AB - We have attempted to produce Escherichia coli strains with the optimal combination of host mutations required for the construction of genomic libraries in lambda and cosmid vectors. For lambda vectors, we defined this as a strain that combined high efficiency of phage plating with optimal tolerance to DNA methylation and the ability to propagate recombinants containing regions of potential secondary structure. To optimize this latter property, we have tested a series of strains for the ability to propagate a lambda phage containing a palindromic sequence. These included an mcr- derivative of a strain shown by Ishiura et al. [J. Bacteriol. 171 (1989) 1068-1074] to allow optimal stability of inserts in cosmid clones. All the sbcC strains allowed plaque formation of the palindrome-containing lambda phage. However, while the palindrome-containing phage plated with reasonable efficiency on SURE (recB sbcC recJ umuC uvrC) and SRB (sbcC recJ umuC uvrC), the majority of phage recovered from these strains no longer required an sbcC host for subsequent plating. These two strains also gave poorer titres with a low-yielding phage clone from the human Prader-Willi chromosome region. Optimal phage hosts appear to be those that are mcrA delta(mcrBC-hsd-mrr) combined with mutations in sbcC plus recBC or recD and without mutations in additional recombination functions such as recJ or recJ umuC uvrC (all of our E. coli strains are available on request). PMID- 8440480 TI - Cloning and analysis of Candida cylindracea lipase sequences. AB - Lipases (Lip) hydrolyze triglycerides into fatty acids and glycerol. Lip produced by the yeast Candida cylindracea are encoded by multiple genomic sequences. We report the molecular cloning and characterization of three genes from this family. They encode putative mature 57-kDa proteins of 534 amino acids (aa). To date, five Lip-encoding genomic sequences from C. cylindracea have been characterized in our laboratory. The five deduced aa sequences share an overall homology of 80%. These sequences have been aligned with each other and with those of homologous enzymes, the Lip from the mould Geotrichum candidum and the acetylcholinesterase from Torpedo californica, whose three-dimensional structures have been solved by X-ray analysis. The C. cylindracea Lip appear to have a structural organization similar to that described for both enzymes. PMID- 8440481 TI - Cloning, sequencing, and heterologous expression of a cellulase-encoding cDNA (cbh1) from Penicillium janthinellum. AB - From a Penicillium janthinellum cDNA library, two clones with 1.8- and 1.9-kb inserts were isolated by hybridization to a Trichoderma reesei cellulase-encoding gene probe (egl1). Both cDNAs have identical 5' ends and coding sequences, but different polyadenylation start points in their 3' untranslated regions. In the nucleotide (nt) sequence, one open reading frame of 537 amino acids was detected which shows 56% homology with endoglucanase I of T. reesei and 70% homology with cellobiohydrolase I of T. reesei, Phanerochaete chrysosporium, and Humicola grisea. Expression of the 1.9-kb cDNA in the Escherichia coli T7 system led to the detection of a 57-kDa protein, in agreement with the theoretical value. Fusion to the promoter of the yeast phosphoglycerokinase-encoding gene led to efficient expression and partial secretion of the cDNA-encoded cellulase with cellobiohydrolase I activity in Saccharomyces cerevisiae. PMID- 8440482 TI - Domain V of Giardia lamblia large-subunit rRNA: structure of the peptidyl transferase loop from an early-branching eukaryote and correlation with antibiotic sensitivity. AB - Large subunit rRNA (LSR) sequences that have been implicated in peptide bond formation form a specific secondary structure called the peptidyl transferase loop (PTL). Although well conserved, the PTLs of eubacteria, archaebacteria, and eukaryotes have several distinct differences. These differences correlate with different sensitivities to peptidyl transferase and translocase inhibitors. To shed light on the basis for these kingdom-specific differences in PTL structure and function, we have analyzed the sequence and secondary structure of LSR domain V, which contains the PTL, from Giardia lamblia. This parasitic protozoan derives from a very early branch in eukaryotic evolution, and its rRNA was previously shown to have bacteria-like features. In vitro and cell-free systems were also used to test the sensitivity of G. lamblia protein synthesis to specific PTL targeted inhibitors. Our results indicate that the PTL structure and inhibitor sensitivity typical of higher eukaryotes is conserved in G. lamblia. However, several adjacent domain V sequences more closely resemble archaebacterial rRNA, confirming the 'primitive' nature of G. lamblia rRNA. Thus, the eukaryotic PTL has been conserved over a vast evolutionary period. We speculate that the eukaryotic PTL is primordial and employs specific RNA-RNA interactions to catalyze protein synthesis. Three potential interactions were identified. PMID- 8440483 TI - The pRSET family of T7 promoter expression vectors for Escherichia coli. AB - A family of eight T7 promoter-based expression plasmids is presented. These are high-copy-number vectors featuring translational start and stop elements and a multiple cloning site (polylinker) with eleven unique restriction sites in all six reading frames. Depending on the cloning strategy used, recombinant proteins may contain either short vector-encoded fusion fragments or no fusion fragments at all. Following promoter induction, proteins are usually produced at a high level. PMID- 8440484 TI - Physical and functional characterization of the ColS8 plasmid. AB - The restriction map of the 5.1-kb colicinogenic plasmid ColS8 is reported. Transposon-insertion mutagenesis has been carried out to investigate the location of the various functional regions of this plasmid. Twenty-six independent ColS8::Tn1 insertions and six different deletion mutant plasmids were isolated, and the locations of the insertions and deletions were determined. The mapping of the transposon-insertion sites, together with characterization of the phenotypes of these mutants, permitted the localization of the regions of DNA involved in colicin production, colicin S8 immunity and mobilization by other plasmids. There is a polar effect in some mutants in which single insertions result in the non expression of all three functions. In minicell preparations, the ColS8 plasmid directed the synthesis of colicin S8 (60 kDa) and a 14-kDa immunity protein. One deletion mutant with a colicin-less phenotype can synthesize colicin S8 in minicells, which placed the DNA region involved in colicin release between the colicin production and immunity regions. Both the 60-kDa and 14-kDa proteins are expressed from pColS8 in maxicell preparations. PMID- 8440485 TI - Synthesis of the Bacillus subtilis histone-like DNA-binding protein HBsu in Escherichia coli and secretion into the periplasm. AB - A synthetic gene encoding the histone-like DNA-binding protein, HBsu, of Bacillus subtilis was cloned in-frame behind the coding region of the OmpA signal peptide of Escherichia coli. The gene encoding the fusion protein is under control of both the lpp promoter and the lac promoter-operator. Upon induction of gene expression, mature HBsu is secreted into the periplasm. The OmpA signal peptide is correctly removed, resulting in the production of authentic-length HBsu protein. The observed in vitro DNA-binding ability is taken as evidence for the correct folding and assembly of homodimeric HBsu protein. A normally intracellular protein can thus be secreted from E. coli in high yield and with full functionality. By analogy, every histone-like protein or mutant forms thereof may be produced heterologously in E. coli and may be purified without being contaminated by the homologous E. coli HU protein. PMID- 8440486 TI - Alzheimer's disease and ageing: a chromosomal approach. AB - Alzheimer's disease (AD) is the most common type of dementia in elderly people. Interrelations between AD and senescence have been the subject of many studies. Some researchers have suggested that chromosomal alterations may be involved in the etiology or pathogenesis of AD. We present cytogenetic findings in patients with Alzheimer's disease, normal elderly controls and young controls. Aneuploidy, premature centromere division, polyploidy and C-anaphase, were analysed and the results suggest that the cytogenetic alterations observed are inherent to the cellular ageing process and not specifically related to Alzheimer's disease. PMID- 8440487 TI - Increased urine interleukin-1 levels in aging. AB - Our laboratory previously noted an increase in thymocyte mitogenic activity in the urine of many elderly patients. The present study was performed to verify this finding and to determine if this activity was actually due to an increase in interleukin-1 (IL-1). IL-1 levels were measured in the urine of 33 healthy, ambulatory, elderly subjects (ages 83-95 years), using both a murine thymocyte bioassay, measuring activation by the incorporation of tritiated thymidine and an MTT dye reduction assay. There was a significant increase in urine IL-1 in 85% of elderly individuals. In the MTT dye reduction assay, mean elderly urine IL-1 levels were 0.88 U/ml, in comparison with a young control group (ages 23-37 years) in which urine IL-1 levels were very low (mean IL-1 < or = 0.05 U/ml). Urine levels of IL-1 beta were also measured by using a sensitive immunoassay (ELISA) and were found to be significantly increased in the elderly (mean = 57.4 pg/ml), compared to the young (mean = 2.5 pg/ml). In contrast, IL-2 levels in urine were very low, with no difference between the young and the elderly. Mean urine protein and creatinine levels did not differ significantly between young and old, and did not account for the increase in urine IL-1 levels. Although its immunologic significance is not yet understood, this striking increase in IL-1 is an unusual and interesting finding that merits further investigation. PMID- 8440488 TI - Potential influence of previous medical pathology on use of thrombolysis in the elderly with suspected acute myocardial infarction. AB - A perceived reluctance by many doctors to consider the use of thrombolytic therapy in elderly patients with acute myocardial infarction prompted us to investigate the potential influence of pre-existing medical pathology on use of fibrinolysis. Of 251 patients consecutively admitted to hospital with suspected acute myocardial infarction, absolute contra-indications to thrombolysis were found in 9 (4%) patients and relative contra-indications in a further 82 (31%) patients. This study suggests that the presence of contra-indications plays a small role in influencing the potential use of thrombolysis in the elderly. Age itself should not be assumed to be inevitably associated with an unacceptable rate of contra-indications for thrombolytic therapy. PMID- 8440489 TI - How common is increased airway reactivity amongst the elderly? AB - A random sample of subjects over 65 years of age who had replied to a postal questionnaire on respiratory symptoms was asked to attend for lung function studies and, if fit, an inhaled methacholine bronchial challenge. Of 283 subjects, 180 (63.6%) agreed to attend. Most (98%) subjects performed reproducible spirometry, with no evidence of fatigue on repeated testing. However, 20 subjects were found to be unsuitable for challenge (forced expiratory volume in 1 s, (FEV1) < 1 litre or unable to perform spirometry reproducibly). The dose of methacholine producing a 20% fall in FEV1 was termed the PD20. A positive challenge with PD20 < 6.13 mumol methacholine was found in 69 of 160 (43%) subjects studied, with highly reactive airways (PD20 < 1.0 mumol methacholine) in 19 of 160 (12%). Bronchial hyperreactivity, which is closely associated with clinical asthma, was found to be far more common amongst the elderly than previously recognised. Low initial FEV1 (1-1.5 litres) predisposed to both a positive challenge (p < 0.01) and also to highly reactive airways (p < 0.01), generally associated with respiratory symptoms. Subjects with low (1-1.5 litres) baseline FEV1 were five times more likely to have highly reactive airways than those with FEV1 > 1.5 litres, confirming a relationship between baseline airway calibre and bronchial reactivity. Early detection of subjects with low FEV1, who are therefore more likely to have increased airway reactivity, may help to reduce respiratory morbidity in the elderly with considerable benefit both to patients and to the Health Service. PMID- 8440490 TI - Is renal biopsy justified for the diagnosis and management of the nephrotic syndrome in the elderly? AB - During the past decade, controversy has raged about the necessity of renal biopsy for the management of the idiopathic nephrotic syndrome. The debate has centered on whether a precise diagnosis is imperative for steroid treatment or whether such therapy can be given blindly. The above question has not been addressed in the elderly. In this retrospective study 30 patients aged > 60 years, all of whom underwent a renal biopsy for an unexplained nephrotic syndrome, were categorized according to histological findings and clinical evolution of their disease. The spectrum of histology was diverse, the most common renal lesion diagnosed being membranous glomerulopathy (MGN) (23%). At variance with other works is the relatively high incidence of membranoproliferative glomerulonephritis (MPGN) (20%) found by us. Minimal change disease (MCD) and amyloidosis were encountered in 5 (17%) and 4 patients (13%), respectively. Specific therapy (steroids) was administered in 11 patients. No benefit of steroid treatment was shown in patients with either MGN or MPGN. The only lesion which responded to steroids was MCD (3 complete remissions, 1 partial). Only one biopsy was complicated by a clinically significant perirenal hematoma requiring blood transfusion. No surgical intervention was necessary. Our findings tend to favor a positive approach to the performance of a renal biopsy in the management of the nephrotic syndrome in the elderly. PMID- 8440491 TI - Autopsy and multiple pathology in the elderly. AB - We examined autopsy reports and the clinical diagnoses of 600 patients (200 in 1967 and 400 in 1987). For each patient we considered age, diagnostic error, main diseases and presence of multiple pathology. The number of diagnostic errors increased from 1967 to 1987. The diagnostic error was particularly high for pulmonary embolism and septic shock and significantly higher in patients > 65 than < or = 65 years old. Multiple pathology was higher in old patients: we found 4 or more diseases in 195/270 (72.2%) patients > 65 years and in only 135/330 (40.9%) patients < or = 65 years. The average period of hospitalization was directly proportional to the number of diseases present in the same patient. PMID- 8440492 TI - Modulation of membrane phospholipid fatty acid composition by age and food restriction. AB - Phospholipids from liver mitochondrial and microsomal membrane preparations were analyzed to further assess the effects of age and lifelong calorie restriction on membrane lipid composition. Results showed that the major phospholipid classes, phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol and cardiolipin did not vary significantly with age or diet. The fatty acid composition of the phospholipids was determined in PC and PE and ages of 6, 12 and 24 months. The data revealed characteristic patterns of age-related changes in ad libitum (AL) fed rats: membrane levels of long-chain polyunsaturated fatty acids, 22:4 and 22:5, increased progressively, while membrane linoleic acid (18:2) decreased steadily with age. Levels of 18:2 fell by approximately 40%, and 22:5 content almost doubled making the peroxidizability index increase with age. In addition, levels of 16:1 and 18:1 decreased significantly with age, indicating a possible change in delta 9-desaturase activity coefficient. Food restriction resulted in a significant increase in levels of essential fatty acids while attenuating levels of 22:4, 22:5, 22:6 and peroxidizability. We concluded that the membrane-stabilizing action of long-term calorie restriction relates to the selective modification of membrane long-chain polyunsaturated fatty acids during aging. PMID- 8440493 TI - New perspectives on the affordability of long-term care insurance and potential market size. AB - A study of over 6,000 elderly long-term care insurance purchasers shows that the typical policy sold costs $102 per month, covers 5 years of nursing home care and pays $69 per day in benefits. Close to one-third of the purchasers have incomes less than $20,000, most (63%) use some savings to pay for premiums, 37% spend more than 5% of income on policies. Most nonpurchasers cited reasons unrelated to policy cost to explain why they did not buy a policy. PMID- 8440494 TI - Maintaining continence in nursing home residents through the application of industrial quality control. AB - Supervisory nurses in seven nursing homes were taught how to implement a quality control management system that permitted the time-efficient assessment of how well a prompted voiding toileting program continued to be implemented by indigenous nursing aides. Random-hour wet checks taken during the 6-month management period revealed a reduction in wetness from 43% to 21% (p < .0001), which was sustained over the full 6-month period. PMID- 8440495 TI - Using telecomputing to provide information and support to caregivers of persons with dementia. AB - The Alzheimer's Disease Support Center (ADSC) is a telecomputing-based project designed to provide information and support to caregivers of persons with dementia. Inherent features of telecomputing make computer-mediated information and support systems like the ADSC a viable complement to existing efforts to meet caregivers' needs. This article outlines the rationale for the ADSC and describes its context, structure, content, and operation. PMID- 8440496 TI - A model abuse prevention program for nursing assistants. AB - This article describes the development, implementation, and evaluation of a model abuse prevention curriculum designed for nursing assistants. Findings from the evaluation showed high satisfaction with the program and improvement on a number of indicators, including reduced conflict with and abuse of residents. PMID- 8440497 TI - Gender and age differences in religiosity among black Americans. AB - Gender and age differences were examined in over a dozen religious indicators using cross-sectional data from the National Survey of Black Americans (N = 2,107). Although both genders manifested moderate to high levels of organizational, nonorganizational, and subjective religiosity, black women significantly exceeded black men in levels of religiosity at all ages, even when controlling for the effects of education, marital and employment status, region, urbanicity, and health satisfaction. PMID- 8440498 TI - Same-gender and cross-gender friendships among the frail elderly. AB - In this article, both the same-gender and cross-gender friendships of a small group (N = 22) of elderly Social Service Department clients in England are described, largely in qualitative terms. The paper raises issues about the importance of cross-gender friendships to the housebound, about gender differentiation within friendships, and about the different characteristics of the two kinds of friendships--ideas that need to be tested in larger, more representative studies. PMID- 8440499 TI - Predictors of use of paid help among older people living in the community. AB - We examined the impact of level of impairment, access to informal services, and household income on the use of paid help by impaired older people using data from the Supplement on Aging to the 1984 National Health Interview Survey. Consistent with previous research, results indicate that impaired elders turn to paid help when informal resources are unavailable. Paid help is more prevalent among elderly people with adequate economic resources and with access to entitlements. Income exerts the greatest impact on situations in which older people have the most discretion regarding acceptance of and sources of help. PMID- 8440500 TI - The labor market for home care workers: demand, supply, and institutional barriers. AB - Increasing demand for paraprofessional home care workers is already straining the quantity and quality of workers entering the field. The author describes variables that affect the supply and demand for home care workers, barriers to change in the home care labor market, and the importance of the government as a key variable in any discussion of the home care labor market. PMID- 8440501 TI - Work life improvements for home care workers: impact and feasibility. AB - Four work life demonstration projects designed to upgrade home aide employment, reduce turnover, and increase continuity of care were evaluated using randomly selected experimental and control groups at each of 11 agencies. The projects reduced worker turnover in the experimental groups from 10 to 44 percentage points. Where it was measured, continuity of care also significantly improved. Local political, economic, and competitive conditions affected the viability of the projects, which added from $.09 to $1.43 to the aides' hourly wage. PMID- 8440502 TI - Home care reimbursement and effects on personnel. AB - Reimbursement policy plays a critical role affecting the ability of providers to recruit and retain paraprofessional home care workers in an industry heavily influenced by public funding. In this article, estimates of paraprofessional home care revenue and size, the composition of the industry, and the workforce incentives inherent in different forms of reimbursement are presented. The findings from this review indicate that the industry's reliance on public funding places special importance on payment policies that recognize the critical role of trained caring staff in meeting long-term care policy goals. PMID- 8440503 TI - Home care quality and the home care worker: beyond quality assurance as usual. AB - Using data from diverse sources, we conclude that the jobs of paraprofessional home care workers who provide ongoing care for older clients would be more intrinsically rewarding and offer better conditions for high-quality care if workers had more contact with supervisors and peers, more information about clients and care plans, clearer accountability, and more authority. The home care worker's relationship with clients, which also affects quality of care, can be improved by addressing such issues as adequate compatibility, communication, boundary maintenance, balance of power, commitment, and flexibility. PMID- 8440504 TI - Public attitudes about the use of chronological age as a criterion for allocating health care resources. AB - We present the first systematic national survey of public opinion on age-based rationing of health care resources. Older people were oversampled in order to allow more precise comparisons of attitude by age cohort as well as by other demographic variables. We found that the majority of people accept the withholding of life-prolonging medical care to hopelessly ill patients, but few would categorically withhold such care on the basis of age. The majority of all ages felt that it was the duty of individual patients regardless of age to refuse medical care that is likely to be futile. PMID- 8440505 TI - Cultural and noncultural factors as determinants of caregiver burden for the impaired elderly in South Korea. AB - This study investigated the determining variables of caregiver burden in caring for impaired older relatives in South Korea. Economic factors, daily caregiving hours, and caregiver's health status emerged as the most important determinants of caregiver burden in Korea. Though not a powerful predictor, caregivers' congruency with the traditional caregiver selection norms remained a statistically significant predictor of certain dimensions of caregiver burden. PMID- 8440506 TI - Implementation of recommended guardianship practices and outcomes of hearings for older persons. AB - We analyzed 1,160 court records to determine whether implementation of recommended procedural safeguards and guardianship practices was associated with outcomes of hearings for older persons. The presence of the proposed ward at the hearing was not related to decisions about guardianship. Proposed wards who retained their own counsel were more likely to receive limited guardianships or have the petition denied. Wards with undefined court-appointed counsel more often received full guardianships than those without representation. PMID- 8440507 TI - The elderly driver: deciding when to stop. AB - This study examines the decision of people (N = 56) living in retirement communities to quit driving, and the role of their physician and family in making this decision. Most of the elderly stopped driving when a threshold was reached after an accumulation of compensatory behaviors. Few stopped because of their doctor's advice, although all felt a physician was in the best position to evaluate driving, and family involvement received limited support. PMID- 8440508 TI - The administration of eligibility for community long-term care. AB - Eligibility assessment systems for community long-term care vary widely across current programs funded by states and Medicaid and in proposals to expand federal funding. Improved equity and efficiency in both current and proposed programs will require better specification of eligibility criteria, timing and setting of assessments, language of assessment items, training of assessors, procedures for appeal and review, and consideration of the costs of care management. Recent research and demonstrations provide models and technology for more uniform approaches in national programs. PMID- 8440509 TI - [Early and presymptomatic detection of Huntington chorea]. AB - This review summarises the techniques for early and presymptomatic testing of Huntington's chorea, a chronic neurodegenerative disorder. Presenting electrodiagnostic, neuroradiographic and neuropsychological measurements, the problem of early detection of this hereditary disorder is discussed. Presently, except for DNA-testing, none of the tests presented can reliably identify symptom free gene carriers. PMID- 8440510 TI - [Schizophrenia and birth seasonality--contrary results in relation to genetic risk]. AB - In 1299 DSM III-R schizophrenics a slight excess of winter and spring births was evident when compared to the general population. However, when patients were allocated to different diagnostic subgroups according to the Leonhard classification this remained true only for those forms without obvious genetic loading (cycloid psychoses and systematic schizophrenias). On the contrary those forms with high genetic loading (unsystematic schizophrenias) showed a clearcut decrease of births in these months. This decrease, however, was significantly caused by periodic catatonics and cataphasics, but not by affect-laden paraphrenics. The findings corroborate the hypothesis that exogenous noxious agents, present in a crucial period of brain maturation, may be of etiological significance in schizophrenia with low genetic loading. Further, it was suggested that in some foetuses at high genetic risk for the disorder more abortions, stillbirths, postnatal deaths and early childhood deaths can occur, if additional exogenous noxious agents affect these individuals. PMID- 8440511 TI - [Normal and frequent neurologic findings in elderly patients]. AB - Numerous normal age-related changes that occur in the nervous system differ more quantitatively than qualitatively from certain common neurological diseases of elder individuals. Changes in the cranial nerve examination primarily relate to an age-related decline in sensory functions, especially of vision and hearing, and to a restriction in the range of eye movements, especially vertically. A progressive decline in the bulk and strength of muscles and in the speed and coordination of movements has long been recognised as an accompaniment of aging. Posture and gait show conspicuous changes with advancing age, partially correlating with diminished sensation in the legs and/or with a nonspecific bradykinetic senile gait. The distal depression of deep tendon reflexes and sensory function is primarily due to distal degeneration of sensory axons. Among the release signs, only the reappearance of the grasp reflex is a reliable sign for indicating pathology of the nervous system. Senile tremor, a decline in the maintenance of thermal homoeostasis, an increasing frequency of orthostatic hypotension, and disorders of sleep are also commonly associated with aging. PMID- 8440512 TI - Analysis of the hormonal control of female sexual behavior and the preovulatory LH surge in the ewe: roles of quantity of estradiol and duration of its presence. AB - Dose-response relationships have been suggested for the role of estradiol (E2) in the induction of both the LH surge and estrous behavior in the ewe. However, it is not always clear whether it is the amount of E2 or the length of time that E2 is present that is important. Furthermore, in previous studies, the intensity of sexual behavior has rarely been studied quantitatively. Our aims in this work were to analyze in more detail the effects of two injected doses of estradiol benzoate (25 or 50 micrograms) for the induction of both the LH surge and estrous behavior (experiment I) and to dissociate the roles of quantity and duration of presence of E2 as administered by implants (experiment II). Increasing the dose of E2 in both experiment I and experiment II decreased the latency to onset of both the LH surge and the receptivity. The duration of E2 presence marginally affected the latency of both responses and the duration of the LH surge. By contrast, the duration of receptivity depended largely on the duration of E2 presence (experiment II: r = 0.569, P < 0.01). This result explains the dose duration effect mentioned previously in the literature and found in experiment I. The maximum response increased with dose in both experiment I and experiment II for receptivity and only in experiment I for the LH surge. We conclude that, at estrus, E2 acts in a similar fashion to induce receptive behavior and the LH surge but controls the maximum levels and the duration of these endocrine and behavioral responses differently. PMID- 8440513 TI - Brain lesions affect penile reflexes. AB - Electrolytic lesions of several potential brain afferents to the spinal nucleus of the bulbocavernosus (SNB) affect the display of penile reflexes. Ablation of the median and pontine raphe areas significantly potentiates the expression of cups and flips. Animals with a bilateral lesion of the paraventricular nucleus of the hypothalamus have a shorter latency to the first erection but otherwise display normal reflex behavior. Although bilateral destruction of the lateral vestibular nucleus (LVN) completely eliminated penile reflex activity, it also caused significant motor impairment thus clouding conclusions concerning the normal role of the LVN in penile reflex behavior. These and other results support the hypothesis that these brain regions which project to the SNB region normally modulate spinal reflex behavior of the rat penis. PMID- 8440514 TI - Persistent effects on maternal aggression of pregnancy but not of estrogen/progesterone treatment of nonpregnant ovariectomized rats revealed when initiation of maternal behavior is delayed. AB - Two experiments explored the effects on subsequent maternal aggression of interspersing 5-24 days between pregnancy termination and pup exposure to elicit maternal behavior. Pregnancy-terminated females displaying maternal behavior were compared to nonpregnant females also stimulated by pups to behave maternally and to pregnancy-terminated groups that were not exposed to pups. Pregnancies were terminated by hysterectomy-ovariectomy on Gestation Day 19 (G19), with pup exposure commencing after 6 days (Expt. 1), and by Cesarean section + ovariectomy (OVX), after delays of 5, 10, or 24 days (Expt. 2). In each study pregnancy terminated, maternal groups were more aggressive than both nonpregnant, maternal groups and pregnancy-terminated, nonmaternal groups regardless of the imposed delays. In Expt. 2, postsurgical interval also was a significant factor, suggesting that surgical stress may elevate maternal aggression for several days. Prolonged treatment of nonpregnant OVX females (Expt. 3) with estrogen and progesterone elevated maternal aggression when pup exposure commenced 2 but not 7 days after termination of hormone treatment (Expt. 3). Therefore the physiological changes initiated during pregnancy that support maternal aggression persist for at least 4 weeks and may involve factors in addition to ovarian hormones that stimulate maternal behavior and maternal aggression. An additional unexpected finding was that nonpregnant (OVX) females had significantly higher Aggression scores after initiating maternal behavior. PMID- 8440515 TI - Corticosterone during the annual reproductive cycle and in sexual behavior in the crested newt, Triturus carnifex. AB - To clarify the role of corticosterone in the male and female crested newt, Triturus carnifex, and the possible involvement of this hormone in the reproductive processes, we monitored the seasonal and daily pattern of this corticosteroid; in addition, corticosterone, testosterone, and 17 beta-estradiol plasma levels were evaluated during the various phases of courtship. In both sexes, the seasonal pattern of corticosterone in plasma showed two peaks: one in winter, at the beginning of the reproduction, and the other one in summer, when the newts leave the pond. The corticosterone daily pattern showed a peak at 05:00 PM. During courtship, corticosterone was lower and testosterone higher in "inactive" male newts than in the courting animals, while estradiol was highest during the approach; in the females corticosterone was lower in "nonreceptive" animals than in "receptive" ones, and sex steroids did not show any difference. These data suggest that corticosterone is involved in the reproductive processes in male and female crested newts. PMID- 8440516 TI - Prostaglandin-induced female spawning behavior in goldfish (Carassius auratus) appears independent of ovarian influence. AB - This study was conducted to determine whether prostaglandin f2 alpha (PGF) induced spawning behavior in female goldfish (Carassius auratus) is influenced by sex steroids or by the stage of ovarian development (assessed by gonadosomatic index (GSI), ovary weight expressed as a percentage of body weight). In two groups of intact females with GSI values ranging from 0.2 to 16.6% (Experiment 1) and 0.6 to 12.7% (Experiment 5), respectively, there was a significant positive correlation between PGF-induced spawning behavior and GSI; however, within either the previtellogenic fish (GSI < 2.5%) or vitellogenic fish (GSI > 2.5%) of either experiment, the correlation between PGF-induced spawning and GSI was not significant. In one ovariectomy experiment, PGF-induced spawning behavior in ovariectomized fish remained equivalent to that of intact and sham fish between 3 and 13 weeks postsurgery. In a second ovariectomy experiment, ovariectomy did not decrease PGF-induced spawning of ovariectomized fish below presurgery levels, but did result in postsurgery spawning that was significantly less than that of intact and sham fish. At 4 weeks postovariectomy, PGF-induced spawning in females that had received blank silastic implants at surgery was no different from spawning of ovariectomized females implanted with either testosterone or 17 beta estradiol. PGF-induced spawning also was unaffected by injection of the oocyte maturation-inducing steroid 17 alpha, 20 beta-dihydroxy-4-pregnen-3-one 16 hr before PGF injection. Together the results indicate that factors associated with ovarian development have only minor influence at most on PGF-induced female spawning behavior, and support earlier proposals that female sex behaviors in externally fertilizing vertebrates are regulated not by ovarian steroids but by prostaglandins synthesized when ovulated oocytes are in the reproductive tract. PMID- 8440517 TI - Treatment of young rams with an agonist of GnRH delays reproductive development. AB - The objective of this study was to determine if the continuous treatment of young rams with an agonist of gonadotropin-releasing hormone (GnRH) in the period immediately prior to puberty would delay the onset of adult sexual behavior and retard testicular development. In the first experiment the GnRH agonist was shown to be effective in suppressing the plasma concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in adult wethers (neonatally castrated rams) when administered by either a biocompatible slow release implant (implant) or a mini osmotic pump (minipump) that released the agonist for 4 weeks. The minipumps were more effective than the implants in suppressing the secretion of LH and FSH. In a second experiment, administration of the GnRH agonist by implant or minipump to prepubertal rams for 16 weeks immediately prior to puberty inhibited the development of sexual behavior, reduced the plasma concentrations of testosterone, retarded testicular and epididymal development, and inhibited growth rates. The effects on sexual behavior were clearly reversible but testicular and epididymal weights were still reduced in treated rams 8 weeks after the end of treatment. These results indicate that the reproductive function of rams is sensitive to gonadotropins and testicular hormones immediately prior to puberty. The agonist of GnRH was successfully delivered to the rams in a biocompatible implant which may offer a practical means of manipulating reproductive function in young rams. PMID- 8440518 TI - Excitotoxic amino acid injections into the medial amygdala facilitate maternal behavior in virgin female rats. AB - The inhibitory role of the medial amygdala (MA) in maternal behavior control was explored. Injections of N-methyl-D,L-aspartic acid (NMA), an excitotoxic amino acid, into the MA resulted in a dramatic facilitation of maternal behavior in virgin female rats when pups were presented to them 12 days following the injections. This effect was specific to MA in that NMA injections into the basolateral amygdala were ineffective. The facilitatory effect of NMA injections into MA was found to be hormone dependent in that ovariectomies abolished the effect. Subsequent experiments provided evidence that NMA injections into MA induced a pseudopregnant state lasting about 13 days, and that maternal behavior was greatly facilitated only when pups were presented to such females coincident with pseudopregnancy termination. When pups were presented 24 days following injections of NMA into MA, rather than 12 days, only a modest facilitation of maternal behavior was observed. It was concluded that NMA injections into MA influence maternal behavior in two ways: By inducing an hormonal state stimulatory for maternal behavior and by removing neural inhibition over maternal behavior. PMID- 8440519 TI - Anuran calling circuits: inhibition of pretrigeminal nucleus by prostaglandin. AB - Neural correlates of mating calling and pulmonary respiration were recorded from isolated brain stems of male Northern leopard frogs (Rana p. pipiens) before and after exposure of the brain stems to prostaglandin F2 alpha (PG) or saline. Diffusion of PG (but not saline) from a pipette directly over the pretrigeminal nuclei abolished "calling" temporarily. Similar application of PG nearby had no effect. Exposure of only the anterior 1/2 of the brain stem, containing the pretrigeminal nuclei but not the pulmonary respiration generator, to PG (but not saline) abolished generation of slow waves by the pretrigeminal nucleus portion of the mating calling pattern generator. Exposure of only the posterior 1/2 of the brain stem, containing the pulmonary respiration generator but not the pretrigeminal nuclei, to PG had no effect on the correlates of pulmonary respiration. These results are consistent with the hypothesis that the inhibition of calling by PG is through an effect largely, perhaps exclusively, on the pretrigeminal nuclei. PMID- 8440520 TI - Testosterone, antiandrogen, and alloparental behavior in bobwhite quail foster fathers. AB - Vasectomized male Texas bobwhite quail (Colinus virginianus texanus) are used as foster fathers in a program to reintroduce the endangered masked bobwhite quail to its native habitat. Less than half of the Texas bobwhite, however, show appropriate alloparental behavior toward the chicks. They also undergo a significant decline in testosterone (T) after 3 to 4 days exposure to the chicks. Males that do not show alloparental behavior undergo a significant increase in T during the same exposure to chicks. Implants containing the antiandrogen flutamide do not affect the courtship and copulation behavior of mated bobwhite males, but flutamide implants do decrease the tendency of these males to act aggressively in the presence of an intruder into the pen of the pair. Flutamide implants do not, however, increase the probability that the males will exhibit alloparental behavior toward chicks that are not their own. Implants containing a mixture of flutamide and ATD (an aromatization inhibitor) also do not increase alloparental behavior. We conclude that while blocking the behavioral effects of T may be necessary for the expression of parental or alloparental behavior, it is not sufficient, suggesting that some other hormonal change may also be necessary to stimulate parental care of precocial chicks. PMID- 8440521 TI - Cell membrane antigen-antibody complex dissociation by the widely used glycine HCL method: an unreliable procedure for studying antibody internalization. AB - Methods following the process of binding and internalization of antibodies to cell surface antigens have often employed low pH isoosmolar buffers in order to dissociate surface antigen-antibody complexes. One of the most widely used buffers is a 0.05 M glycine-HCL buffer pH 2.8. Since the efficacy of action of this buffer was critical to a series of internalization experiments employing monoclonal antibodies (Mabs) to carcinoembryonic antigen (CEA) expressing cancer cell lines in this laboratory, we tested its performance in a number of different assays. Our results indicate that this buffer only partially dissociates antigen antibody bonds and therefore can introduce major inaccuracies in internalization experiments. PMID- 8440522 TI - Interleukin-2-responsive wound-infiltrating lymphocytes in surgical adjuvant cancer immunotherapy. AB - Wound-infiltrating lymphocytes (WIL) were assessed in murine models of localized sarcoma and carcinoma to evaluate the role of interleukin-2 (IL-2)-responsive lymphocytes in adjuvant immunotherapy. Following tumor resection, IL-2 or diluent was injected at the surgical site for 6 days. Surgical site tissues were harvested and digested in a triple enzyme mixture, and single cell suspensions were prepared. Thy 1.2+ lymphocytes were isolated by incubating cells with monoclonal anti-Thy 1.2 antibody-coated magnetic beads. Lymphocyte-bead complexes were extracted with a magnet and cultured in medium containing IL-2 (100 units/ml) for 1-3 weeks. Perioperative IL-2 immunotherapy led to a three- to four fold increase in WIL yield. WIL from IL-2-treated mice also demonstrated enhanced cytolysis of the autologous tumor and bound to activated endothelial cells with greater avidity than did the controls. We conclude that perioperative IL-2 therapy augments the yield, as well as the cytolytic and adhesive properties, of wound-infiltrating lymphocytes. PMID- 8440523 TI - Adherence of blood T cells to rat microvascular endothelial cells. Comparative studies of T lymphocytes isolated from various tissues. AB - Lymphocytes isolated from various tissues exhibit different magnitudes of adherence to endothelial cells (EC) in vitro. Nevertheless, a good correlation between the lymphocyte adherence to EC in vitro and their migratory properties to sites of inflammation in vivo was found. The main goal of this study was to compare, using unstimulated and IFN-gamma-, TNF-alpha- or LPS-pretreated EC, the adherence of T cells isolated from blood (BTC), with the adherence of T lymphocytes obtained from other tissues. The results show that BTC belong to poorly adhering cells. However, their adherence was increased about 3-fold, when EC were pretreated with IFN-gamma, TNF-alpha or LPS. This adherence was very similar to that observed for lymph node T cells (LNTC) and 2-3 times lower than the adherence of spleen T cells (SpTC) and peritoneal exudate T cells (PETC). In some experiments, T lymphocytes were incubated for 1 h with concanavalin A (Con A) and this led to the highest increase of BTC adherence, but the enhancement of the adherence was significantly smaller than the increase noted for SpTC and PETC. The differences in the adherence of lymphocytes isolated from various tissues may suggest that different adhesion molecules are responsible for their binding to EC. PMID- 8440524 TI - Monoclonal antibody prophylaxis against the in vivo toxicity of ricin in mice. AB - A BALB/c murine IgG1 monoclonal antibody, designated BG11-G2, specific for ricin was generated. BG11-G2 antibody did not bind to either purified ricin chain A or chain B, but recognized an antigenic determinant whose conformation requires the combination of the two chains in the formation of the native ricin molecule. It did not react with the protein synthesis inhibitor, T-2 mycotoxin, or with the sodium channel blockers, saxitoxin and tetrodotoxin. As little as 0.78 micrograms/ml of BG11-G2 IgG1 anti-ricin monoclonal antibody completely protected against the in vitro toxicity of ricin as determined by [3H]leucine uptake in EL 4 cell assays. Passive intraperitoneal infusion of purified BG11-G2 antibody into BALB/c mice one day prior to a lethal challenge with ricin considerably delayed the onset of toxicity and death. Better protection was obtained with BG11-G2 infused before and after ricin challenge. PMID- 8440525 TI - Effects of anesthesia on micturition and urodynamics. PMID- 8440526 TI - Pediatric renal function. PMID- 8440527 TI - Anesthesia for pediatric urological surgery. PMID- 8440528 TI - Pain management for pediatric urological surgery. PMID- 8440529 TI - Latex allergy and anaphylaxis. AB - Latex allergy is a potential cause of unexplained intraoperative anaphylaxis. Latex allergic reactions range from mild wheal and flare episodes to cardiovascular collapse. High-risk patient populations merit latex allergy testing. Preoperative prophylactic regimens may prevent or attenuate serious intraoperative latex allergic reactions in susceptible individuals. Additional work is needed to better characterize and understand latex allergy. PMID- 8440530 TI - Anesthesia for transurethral prostate surgery. PMID- 8440531 TI - Anesthetic considerations for extracorporeal shock wave lithotripsy. PMID- 8440532 TI - Regional anesthesia for urological surgery. PMID- 8440533 TI - Effects of patient positioning during anesthesia. PMID- 8440534 TI - Autonomic hyperreflexia. AB - Autonomic hyperreflexia presents as acute episodes of uninhibited reflex sympathetic hyperactivity in the patient with chronic high spinal cord lesion. An understanding of the pathophysiology of this syndrome is paramount in its successful management. It occurs in patients with chronic spinal cord lesions above T7 upon stimulation below the lesion, particularly distention of the urinary bladder. The main clinical signs are paroxysmal hypertension and bradycardia. Management of acute episodes should include withdrawal of the initiating stimulus and possibly administration of pharmacological agents such as nifedipine and nitroprusside. Long-term treatment may involve radical surgery. Despite its technical difficulties, spinal block is still the anesthesia of choice in these patients. PMID- 8440535 TI - Self-attributed consequences of cocaine use. AB - This study examines self-attributed consequences of cocaine use in a nonclinical sample of 1,270 young adults. A social learning perspective was used to examine the ability of motivational dimensions of use, as well as use patterns, to predict negative consequences of use. Four scales of negative consequences emerged: Negative Effects, Dependency Symptoms, Physical/Social, and Legal/Interpersonal consequences. Reasons for using cocaine, patterns of use, and their interactions significantly predicted negative consequences of use. Those subjects who endorsed coping reasons for use were more likely, while those who endorsed uplift reasons were less likely, to experience negative consequences. PMID- 8440536 TI - Life activities and life quality of heroin addicts in and out of methadone treatment. AB - The focus of the present study was the daily life activities and self-perceived health and life quality of heroin addicts both in and out of methadone treatment, based on 219 addicts followed for 8 months after treatment entry. The majority of outcome evaluations of methadone treatment have focused on the "hard" outcome criteria of drug use levels, criminal activities, and employment. The present study, in contrast, addressed how heroin addicts live on a daily basis, and whether being chemically supported on methadone was associated with changes in daily life activities and perceived quality of life. A six-dimensional measurement model of daily life activities, perceived health, and life quality was established. Substantial changes on the dimensions in a positive direction were found in the 2 months just following treatment entry. Changes in daily life activities (e.g., spending more time with the family, attending to the home) may be early indicators of the impact of methadone treatment that precede changes on the usual "hard" criteria (e.g., obtaining legal employment). PMID- 8440537 TI - Rural youth usage of alcohol, marijuana, and "hard" drugs. AB - Based on developmental theory, this article tests the relationships between first and current use of alcohol, marijuana and "hard" drugs among a sample of 197 rural and small-town youth. Findings indicate that age of first use of alcohol predicts current use of alcohol. The same pattern occurs for marijuana and hard drugs. Age of first use of alcohol is also related to first use of marijuana, which in turn is related to first use of hard drugs. The order is reversed for current use. Current use of hard drugs predicts current use of marijuana, which in turn predicts current use of alcohol. PMID- 8440538 TI - Attitudes toward and beliefs about smoking in grade school children. AB - A questionnaire was developed to study attitudes toward and beliefs about the health consequences and social value of smoking. After initial evaluation of the instrument's reliability, it was administered to approximately 400 children, ranging in age from 7 to 15 years. Significant age effects for some items were demonstrated, but no significant sex effects or sex by age interactions were revealed. Children as young as 7 years were found to be well aware of the health hazards of smoking and likely to express negative attitudes concerning it. We conclude that if smoking prevention programs are to have more than minimal success with youth, they must offer something more than mere information about the health hazards of smoking. PMID- 8440539 TI - Carbohydrate metabolism during exercise in hot and thermoneutral environments. AB - This study compared the effects of moderately intense exercise in hot and thermoneutral environments on muscle glycogen and carbohydrate utilization. Well trained, heat acclimatized cyclists (n = 7) rode at 73.6 +/- 1.1% maximal oxygen consumption for 60 min in a thermoneutral room (23.5 +/- 0.6 degrees C, 52.7 +/- 2.9 relative humidity) or an environmental chamber (33.7 +/- 0.1 degrees C, 49.1 +/- 1.8% relative humidity). During each exercise bout, the subjects received 125 ml of water every 15 min. Muscle biopsies from the vastus lateralis were obtained prior to and following each exercise bout. Exercise in the heat significantly elevated rectal temperature and heart rate above and reduced body weight and plasma volume below that produced by exercise in a thermoneutral environment. Plasma glucose and blood lactate concentrations were similar between treatments prior to exercise, but increased to a greater concentration (p < 0.05) when exercise was performed in the heat. No differences between treatments were found for blood glycerol or free fatty acid concentrations, carbohydrate oxidation or muscle glycogen utilization. These results suggest that moderately intense exercise in the heat, as opposed to a thermoneutral environment, does not increase the rate of muscle glycogenolysis or carbohydrate oxidation in well conditioned, heat acclimatized subjects. PMID- 8440540 TI - Effect of increased plasma non-esterified fatty acid concentrations on endurance performance during beta-adrenoceptor blockade. AB - Inhibition of adipose tissue lipolysis, leading to a reduced availability of non esterified fatty acids for energy production in the active skeletal muscles, may be involved in the impairment of endurance exercise capacity after administration of a beta-adrenoceptor blocking agent. The effect of increasing the availability of plasma NEFA during exercise after beta-blocker administration was studied. In a double-blind, randomized cross-over study 12 healthy volunteers were treated for 14 days with placebo, atenolol, and propranolol. On the 7th and 14th day of each treatment period an endurance exercise test at 70% of maximal aerobic power until exhaustion was performed while a continuous infusion of saline or triglycerides (Intralipid)+heparin was administered. Endurance time was reduced by 11% (n.s.) during atenolol and 40% (p < 0.01) during propranolol. Intralipid administration had no statistically significant effect on endurance in any treatment. Plasma NEFA and glycerol concentrations were elevated above control levels during Intralipid infusion, plasma glucose and lactate concentrations were unaffected. These results suggest that reduced availability of NEFA is not a major factor in the reduction of endurance performance during beta-adrenoceptor blockade, although an effect of beta-blockade on NEFA membrane transport cannot be excluded. PMID- 8440541 TI - Strength training by electrostimulation conditions for efficacy. AB - The overload imposed on the neuromuscular system under Electrostimulation (ES) can be expressed by applied current intensity or by Electrically Evoked Torque (EET). The aim of this study was to discern which of these two parameters is the one which is determinant for the efficacy of training by ES. Test and training involved isometric contraction of the flexion maintained at a joint angle of 25 degrees (0 degree = extension). The 16 trained subjects received 15 sessions of 25 electrically evoked contractions, using a monophasic rectangular waveform current at a frequency of 2500 Hz modulated at 90 Hz. Each stimulation lasted for 5 sec at the maximal tolerable current. Contrary to the control group (n = 16), the trained group significantly increased their MVIC (15.6%). The individual strength gains ranged from -5% to 49%. No correlation was found between current level and strength modifications. A direct relation was established between the EET and the strength gains (a minimum threshold of EET must be reached during at least 8 sessions to induce strength increases). The "overload principle", previously described for voluntary contraction strengthening, seems to be suitable for electrical stimulation and concerns the EET shown on the ergometer as the effect of the contraction of agonist and antagonist muscles. PMID- 8440542 TI - A physiological/psychological indicator of over-reaching during intensive training. AB - Many indicators of over-reaching and over-training have been proposed, using both physiological and psychological techniques. Field testing of athletes has led us to believe that a decrease in the ratio of blood lactate concentration to ratings of perceived exertion indicates a fatigued and/or over-reached state following intensive training. The purpose of this study, therefore, was to test the hypothesis that a decrease in the ratio of blood lactate concentration to ratings of perceived exertion would indicate an over-reached state. Seven well-trained male cyclists performed two weeks each of: normal (moderate) training, overtraining and recovery. During each time period an incremental exercise test was performed to maximal effort with blood lactate concentration (HLa) and ratings of perceived exertion (RPE) obtained for each workload. All seven subjects became over-reached during the two week period of intensive interval training. The ratio of HLa:RPE (multiplied by 100) decreased with all workloads following both one (mean decrease 29.1 +/- 3.0%) and two (mean decrease 48.7 +/- 2.5%) weeks of overtraining. However, only the decrease at the maximal workload was statistically significant. Examining the individual data revealed that at maximal workload all seven subjects had HLa:RPE ratios of less than 100 when over reached. The ease and speed at which the HLa:RPE ratio can be determined may make it useful for coaches and athletes in monitoring intensive exercise training and recovery. PMID- 8440543 TI - Reduced training volume and intensity maintain aerobic capacity but not performance in distance runners. AB - It has recently been shown that a 70% reduction in training volume, while maintaining training intensity, results in the maintenance of VO2 max and 5 km running performance in distance runners. The purpose of this study was to examine the effects of a 4 wk reduction in training volume and intensity in distance runners. Ten well-conditioned males (VO2max = 63.4 +/- 1.3 ml.kg-1 x min-1) underwent 4 wks of base training (BT) at their accustomed training distance (71.8 +/- 3.6 km.wk-1) and intensity (76% of total distance > 70% VO2max). Training volume (-66%), frequency (-50%), and intensity (all running < 70% VO2max) were then decreased for a 4 wk reduced training period (RT). Treadmill VO2max was unchanged with RT (p > 0.05) as were resting plasma volume, estimated from haemoglobin and haematocrit levels, and resting heart rate (HR). Submaximal treadmill exercise VO2 (l.min-1), ventilation and HR were also unchanged, however, submaximal exercise RER and blood lactate accumulation following 4 mins at 95% VO2max (8.39 vs 9.89 mmol.l-1) were significantly elevated by RT (p < 0.05). Estimated percent body fat also increased (10.4% vs 11.8%) (p < 0.05). Five km race completion time significantly increased from 16.6 +/- 0.3 mins at week 4 of BT to 16.8 +/- 0.3 mins (12 seconds) at week 4 of RT. Nine of the 10 subjects were slower after RT. It is concluded that aerobic capacity was maintained in these runners, despite the combined reduction in training volume and intensity. However, it appears that training intensity during RT is important for the maintenance of 5 km running performance. PMID- 8440544 TI - Exercise responses to in-line skating: comparisons to running and cycling. AB - A comparison of the physiological responses to in-line skating with the more traditional modes of exercise training has not been reported. The purpose of this study was to examine the physiological responses to in-line skating compared with running and cycling. Nine trained volunteers (2 male, 7 female) performed 3-6 submaximal (30-90% VO2max) workloads with each exercise mode. Oxygen uptake, heart rate and blood lactate were measured during each trial. Across the spectrum of oxygen uptakes studied, heart rate was higher with in-line skating than with cycling or running. At a lactate concentration of 4 mM, oxygen uptake was less for in-line skating and cycling than for running. Therefore, while in-line skating may be an effective mode of aerobic exercise, the training adaptations for in-line skating at 4 mM lactate may not be as great as for running, and at a given HR may be less than for running and cycling. PMID- 8440545 TI - The effect of moderate resistance weight training on peak arm aerobic power. AB - The purpose of this study was to examine the effect of moderate resistance weight training (MRWT) on peak arm aerobic power as measured by arm cranking ergometry. Fourteen sedentary college age males, divided equally into two groups, served as subjects. The seven subjects in the MRWT group completed 12, 1-hr bouts of weight lifting over a 4 week period, exercising on Monday, Wednesday and Friday of each week. Exercise sessions included 3 sets of 10 repetitions of the following lifts: bench press, overhead dumbbell press, dumbbell arm curl, and behind the neck pull down. The remaining seven subjects served as a non-training control group, whose purpose was to account for possible learning effects on the arm ergometer test that could distort the statistical relevance of the aerobic power data. These subjects did not serve as a control for the weight training exercises, as the procedures used to determine muscular strength may produce a modest training effect. Peak arm aerobic power and muscular strength, as measured by the one repetition maximum for each lift, were determined before and after the training program. The average increase in strength for all lifts combined for the trained group was 20.0%. They also experienced a 13.4% (p < .005) increase in peak arm aerobic power, whereas there was no significant change in this variable for the control group. It is concluded that peak arm aerobic power is enhanced by the changes in muscular strength produced by 4 wks of MRWT. PMID- 8440546 TI - Effect of running exercise on proteoglycans and collagen content in the intervertebral disc of young dogs. AB - Collagen and proteoglycans in the intervertebral disc (LI-II) of young beagle dogs (age 55 weeks) were analyzed following a 15 weeks' daily 20 km running training on a treadmill with 15 degree uphill inclination. In nucleus pulposus no statistically significant alterations were found in the content of proteoglycans or collagen. In annulus fibrosus the total tissue wet weight and total amount of collagen (hydroxyproline) increased by 34-36% in the runners as compared to age matched, untrained controls. Since the total amount of proteoglycans did not increase, the annulus fibrosus became relatively depleted of proteoglycans, as indicated by the 27% reduction in uronic acid concentration, expressed either per wet weight or hydroxyproline. The average molecular size of the remaining nonaggregating proteoglycans was larger, and there was also a trend towards increased proportion of proteoglycans aggregating with hyaluronan. Most of the chondroitin sulfate side chains were 6-sulfated (65-66%). Running did not alter the sulfation or length of the chondroitin sulfate chains. The decreased proteoglycan/collagen ratio in annulus fibrosus may result in altered mechanical properties of the tissue and reflects its adaptation to enhanced motion and stress. PMID- 8440547 TI - Blood glucose following training sessions in runners. AB - The possibility that blood glucose reaches potentially dangerous concentrations following training sessions was investigated in 10 competitive runners. Blood glucose concentration was assayed in the first 60 min following a continuous run at moderate pace for 45 min, a continuous run at hard pace for 30 min, an interval training session for 15 min, and an incremental exercise test to maximum effort. Glucose concentration increased and remained high for up to 30 min following the hard-pace, interval and maximum-effort runs; maximum concentrations (mean +/- SD 6.8 +/- 1.1, 6.8 +/- 1.0, 7.8 +/- 1.1 mmol.l-1 respectively) were significantly higher (p < 0.05) than those of the moderate-pace run (4.9 +/- 0.4 mmol.l-1). A 10-min warm-down at moderate pace dramatically attenuated the surge in glucose concentration following 30 min of hard-pace running, but a pre exercise carbohydrate snack had no effect. Level of glycation of haemoglobin in a venous blood sample (mean +/- SD 4.6 +/- 0.7 %) was normal. Thus transient elevations in blood glucose concentration following high-intensity training sessions are unlikely to damage body proteins. PMID- 8440548 TI - Physically induced pemphigus after cosmetic procedures. AB - BACKGROUND: Pemphigus is a vesiculobullous autoimmune disease characterized by acantholysis due to antibodies against epidermal antigens. CASE REPORTS: We report the first two cases of pemphigus in which lesions appeared in areas traumatized by cosmetic procedures. In one case, the patient had a history of pemphigus under excellent control; pemphigus lesions appeared only in her surgical scars 2 months after a reduction mammoplasty and facelift. The other patient presented with an outbreak of pemphigus 4 weeks after a chemical peel. CONCLUSIONS: Physical agents including infrared and ionizing radiation as well as ultraviolet light are known triggers of pemphigus. We suggest that cosmetic procedures can initiate pemphigus and that this change must be differentiated from postoperative wound infections and other reasons for poor wound healing. PMID- 8440549 TI - Erythema nodosum versus nodular vasculitis. AB - BACKGROUND: Erythema nodosum (EN) is usually considered to be a septal panniculitis, and nodular vasculitis (NV) a lobular panniculitis. We tested the usefulness of this histologic classification in clarifying a frequent clinical dilemma: EN versus NV. METHODS: Over 3 years 109 patients with panniculitis were included in this study. After a history and a physical examination, a clinical diagnosis was made according to well-established criteria. RESULTS: From the study of 88 patients, we concluded that in the clinically typical cases, the clinico-pathologic agreement was 93% and 94% for EN and NV respectively, whereas it diminished to 79%, 72%, and 67% in the cases clinically diagnosed as EN migrans, atypical EN, and atypical NV, respectively. Moreover, septal and lobular panniculitis were always two clear-cut, different, opposite patterns of hypodermal inflammation to these conditions. CONCLUSIONS: In the absence of a known pathogenetic mechanism, the histopathology remains the most objective discriminating marker between EN and NV, mainly in the clinically atypical and doubtful cases. PMID- 8440550 TI - Outbreak of cercarial dermatitis in Thailand. AB - BACKGROUND: An epidemic of cercarial dermatitis caused by Schistosoma spindale cercaria occurred in November 1988 in a district called Chaiya, Surajthani province, in Southern Thailand. CASE REPORTS: Fifty-eight Thai farmers in Chaiya, Surajthani gave a history of itch following immersion in water while planting rice. The area of rice field was flooded for 10 days before farmers started working. The duration of the disease ranged from 2 days to 1 month. Forty-one patients had the disease for the first time, seventeen had a history of previous manifestations. CONCLUSIONS: This epidemic was caused by S. spindale cercaria, which developed in the Indoplanorbis exustus snail, associated with flooding. PMID- 8440551 TI - Sarcoidosis on ritual scarification. PMID- 8440552 TI - Recalcitrant pyoderma gangrenosum responsive to cyclosporine. PMID- 8440553 TI - Widespread nevus spilus. PMID- 8440554 TI - Unilateral facial telangiectasia macularis eruptiva perstans. PMID- 8440555 TI - Unusual case of multicentric reticulohistiocytosis. PMID- 8440556 TI - Scabid: an unusual id reaction to scabies. PMID- 8440557 TI - Intravenous pyogenic granuloma. PMID- 8440558 TI - Psoriasis-like lesions in guinea pigs receiving propranolol. AB - BACKGROUND: beta-Blockers cause a psoriasiform eruption. We investigated the skin effects of systemic propranolol in a formal protocol. METHODS: Propranolol, 0.1 mg/day, was used systemically by gavage in eight albino guinea pigs. Normal saline was given to another group of seven guinea pigs. RESULTS: Propranolol produced psoriasiform lesions in five of seven guinea pigs on the 30th day. Biopsies showed acanthosis, parakeratosis, microabscesses, and cellular infiltration of upper dermis. Topical application of propranolol did not produce clinical psoriasiform changes, while acanthosis and papillomatosis was observed in six of the six guinea pigs. PMID- 8440559 TI - Treatment of paucibacillary leprosy. AB - BACKGROUND: When multidrug therapy was introduced a decade ago to shorten the duration of treatment, paucibacillary leprosy was advocated 6 months of treatment. The diagnosis is based mainly on clinical and histopathologic examination, negative slit-skin smear examination, and positive lepromin test. METHODS: The case records of 508 paucibacillary leprosy patients attending our urban leprosy center have been analyzed with reference to regularity of therapy, response to multidrug regimen, follow-up, and relapse. RESULTS: The incidence of paucibacillary leprosy was found to be 37%. Defaulter rate was 45%. Nine percent of the cases attended the center with deformities emphasizing the need for corrective surgery and early case detection to prevent them. CONCLUSIONS: The main problem that we faced was the optimum duration of treatment, which is as yet an unsettled question. The opinions of other workers have been given, and a slight modification in current WHO regimen has been suggested without significantly affecting the cost of therapy. PMID- 8440560 TI - Intramuscular low dose alpha-2B interferon and etretinate for treatment of mycosis fungoides. AB - BACKGROUND: Mycosis fungoides is a lymphoma of cutaneous origin characterized by a proliferation of cells with a T phenotype. METHODS: In this pilot study, 13 men with mycosis fungoides in various stages were treated with alpha-2b interferon and etretinate. RESULTS: In ten of them, such a therapy proved to be effective (7 complete responses, 3 partial responses), sometimes with prolonged remissions (up to 20 months, and still persistent) after suspension of the drugs. CONCLUSIONS: We chose low-dose interferon administration in order to prevent side effects, which are said to be dose-dependent. In our experience this is not true, but this drawback seems to be overcome by the very good, sometimes spectacular, response to this combination therapy, particularly in low stage forms of the disease. This fact, compared with results provided by other groups, prompts us to plan new research protocols based on associations of retinoids with different interferon types (or even associations of different interferons), because we believe they will have an important place in treatment of cutaneous T-cell lymphoma in future. PMID- 8440561 TI - Classification of skin diseases in nineteenth century America. PMID- 8440562 TI - Space Dermatology Foundation--5th annual seminar "Skin in Space". PMID- 8440563 TI - Disseminated granuloma annulare and intranasal calcitonin. PMID- 8440564 TI - Trichoptilosis caused by misuse of ketoconazole 2% shampoo. PMID- 8440565 TI - Morphology revisited. PMID- 8440567 TI - Chronic bullous dermatoses in China. PMID- 8440566 TI - Psychiatric syndromes of interest to dermatologists. PMID- 8440568 TI - The Fine Page: angiotensin converting enzyme angioedema. AB - Angioedema/urticaria secondary to ACE inhibitor drugs is an important clinical entity, which dermatologists should be aware of as they are so widely used and their use will undoubtedly increase. In addition to the obvious importance to the patient of promptly recognizing ACE inhibitor angioedema, uncovering the etiology of angioedema/urticaria is a rare and satisfying experience that can "make your day." PMID- 8440569 TI - Ultrastructure of Trichophyton violaceum. AB - BACKGROUND: The ultrastructure of different fungi have been described in recent literature; however, few reports have concerned dermatophytes. METHODS: Fine structure of Trichophyton violaceum was observed using electron microscopy. RESULTS: Hyphae appeared as branched segmented filaments with a cell wall consisting of two layers. Thin electron dense plasma membrane was evident continuous with the inner surface of the cell wall. Septal walls with central pores and a uniform electron opacity plugs were seen. The hyphae were multinucleated and the cytoplasm contained endoplasmic reticulum, mitochondria, and vacuoles. CONCLUSIONS: Although these findings showed ultrastructural similarities of the cell wall with Microsporum canis, Microsporum gypseum and Microsporum audouinii, there were some points of difference in the ultrastructure of the hyphae in Epidermophyton floccosum, and in the mitochondria of Trichophyton mentagrophytes as described by other investigators. PMID- 8440570 TI - [What is reliable in the treatment of osteoporosis in menopausal women?]. PMID- 8440571 TI - [Quantity and quality in medicine]. PMID- 8440572 TI - [What is guaranteed in the therapy of alcoholic hepatitis?]. PMID- 8440573 TI - [What is guaranteed in the therapy of hepatic encephalopathy?]. PMID- 8440574 TI - [What is guaranteed in the treatment of gastrointestinal endocrine tumors?]. PMID- 8440575 TI - [Treatment of fecal incontinence. Morphologic and pharmacologic principles]. PMID- 8440576 TI - [42-year-old patient with fever and a palpable abdominal tumor]. PMID- 8440577 TI - [What forms of thromboembolism prevention and therapy can be used in patients with chronic inflammatory bowel diseases?]. PMID- 8440578 TI - [What procedures are applicable, especially in elderly patients, to achieve weaning from an indwelling catheter?]. PMID- 8440579 TI - [Response to the previous comments by P. M. Shah]. PMID- 8440580 TI - [Diagnosis of allergy]. PMID- 8440581 TI - [Pharmacologic therapy of rheumatoid arthritis with delayed-action anti-rheumatic drugs]. PMID- 8440582 TI - Lens-equivalent age controls for diabetics. PMID- 8440583 TI - Congenital nystagmus mechanism. PMID- 8440584 TI - Effect of diltiazem on lid tension during light-flash-induced eye blinks in the rabbit. AB - PURPOSE: The purpose of this study was to examine the effect of the Ca blocker diltiazem in combination with the Ca chelator EGTA (ethyleneglycol-bis-ta-amino ethyl ether]N,N'-tetraacetic acid) on eyelid tension generated during the light induced eyeblink reflex in the adult rabbit. The goal is to develop nontoxic, nonsurgical therapies for blepharospasm. METHODS: Blinks were triggered in the alert rabbit, and tension was measured with a strain gauge attached to the eyelid. Strain gauge output was amplified, digitized, and stored on computer for later analysis. Experiments consisted of a set of trials in which identical light stimuli were delivered at 0.1 Hz for 5 min. RESULTS: In control trials, blink tensions decreased dramatically for the first seven to nine blinks and then levelled off, indicating that with respect to muscle tension output, blinks contained both rapidly habituating and nonhabituating components. After diltiazem and EGTA were injected in the lid, blinks were reduced 30% to 90% over those in control trials. Reductions could not be explained by injection trauma or irritation due to fluid volume, because injections of saline alone did not produce such tension depression. CONCLUSIONS: Diltiazem-EGTA produces a transient reduction in blink tension. A clinical application will depend on developing methods for the sustained release of these drugs in the eyelid. PMID- 8440585 TI - Plasma membrane internalization and recycling in rabbit lacrimal acinar cells. AB - PURPOSE: The purpose of this study was to examine internalization and recycling of plasma membrane constituents in lacrimal gland acinar cells. METHODS: Acinar cells were isolated from rabbit lacrimal glands. Surface-expressed reactive groups were biotinylated at 4 degrees C with sulfo-N-hydroxysuccinimidyl-biotin. Incorporated biotin was then labeled with avidin-horseradish peroxidase complex for light microscopy, with avidin-lucifer yellow conjugate for fluorescence microscopy, and quantitative fluorometry, and with avidin-ferritin conjugate for electron microscopy. RESULTS: At 4 degrees C labels remained at the surfaces of intact cells. Surface avidin-lucifer yellow decreased markedly, giving way to punctate cytoplasmic labeling, on warming to 37 degrees C. Electron microscopy of cells warmed after labeling with avidin-ferritin revealed ferritin in smooth vesicles underlying the plasma membranes, in vesicles adjacent to Golgi membranes, and in multivesicular bodies. Incubation at 37 degrees C before chilling and labeling with avidin-lucifer yellow decreased the cells' capacity to bind avidin-lucifer yellow by 95%, with t0.5 < 0.5 min. If cells were then incubated with avidin-lucifer yellow at 37 degrees C, they took up the marker with a time course that indicated that 60% of the initial biotin either recycled back to the plasma membrane or remained in intracellular compartments that could be reached by endocytosed extracellular fluid. Internalized biotin communicated with extracellular avidin-lucifer yellow with a t0.5 of 2 min, and this process was accelerated by carbachol at concentrations of 10 mumol/l and 1 mmol/l. CONCLUSIONS: Acinar cell plasma membrane constituents participate in an ongoing, secretagogue-modulated recycling traffic between small surface-expressed pools and 10- to 20-fold larger intracellular pools. PMID- 8440586 TI - Eyelid opening induces expression of a glycocalyx glycoprotein of rat ocular surface epithelium. AB - PURPOSE: We previously characterized a monoclonal antibody against a glycoprotein of rat ocular surface glycocalyx (ROSG). This monoclonal antibody recognizes a carbohydrate epitope on a glycoprotein expressed in apical cells of the differentiated ocular surface epithelium. Our goal was to determine the developmental appearance of the ROSG glycoprotein. METHODS: We localized the antigen immunohistochemically and immunocytochemically in newborn (day 1) rats and in rats 2-5, 7, and 11-15 days after birth. RESULTS: Before eyelid opening (days 12-14), the ROSG antigen was localized in the palpebral conjunctiva near the lid margin. The binding extended to layers of the subapical flattened cells. However, the antigen was not found in the corneal epithelium while the eyelid remained closed. In contrast, at the first day of eyelid opening (days 12-15), the antigen was present contiguously in several cell layers from the eyelid margin along the entire ocular surface, including the corneal epithelium. Thus, the binding pattern seen upon eyelid opening was similar to that of adult rats. The phenomenon of appearance of the glycoprotein upon eyelid opening was further demonstrated in rats with asynchronous eyelid opening. Artificial, premature eyelid opening at days 8-11 also induced the expression of the antigen along the entire ocular surface epithelium, similar to the binding in naturally opened eyes. CONCLUSION: Eyelid opening may induce glycosylation or expression of a glycocalyx component that we hypothesize to be involved in mucin spread. PMID- 8440587 TI - Histochemical distribution of carbonic anhydrase in rat and rabbit lacrimal gland. AB - PURPOSE: The purpose of this study was to examine the histochemical distribution of carbonic anhydrase (CA) in lacrimal glands from rats and rabbits; and to determine if age- and/or sex-related differences exist in the amount and distribution of CA in the rat lacrimal gland. METHODS: Lacrimal glands from young (3-12 wk) and aged (2-2.5 yr), male and female F344 rats and male rabbits were fixed in 1% paraformaldehyde and embedded in glycolmethacrylate. CA histochemistry was performed on 2-microns sections. The distribution of CA activity was determined by morphometric analysis. RESULTS: In rat lacrimal gland, CA activity was distributed in a discontinuous, mosaic fashion among the acinar cells. In tissue from young males and females as well as from aged females, about 10% of the acinar tissue displayed CA activity. Significantly more activity was present in tissue from aged male rats. CA was present in the ductal lumina, suggesting that it is a secretory product of the acinar cells. In rabbits, CA activity was associated with the basolateral membranes of the terminal acinar cells only. CONCLUSIONS: In rat, the presence of CA activity in certain acinar cells and in ductal lumina suggests that CA is actively secreted by the lacrimal gland. An age-related increase in the amount of CA activity in the male glands exists that may be under gender-specific hormonal influences. In the rabbit lacrimal gland, the membrane-associated CA found uniquely with the terminal acinar cells suggests that these cells have special transport functions associated with the primary secretion of lacrimal fluid. PMID- 8440588 TI - Light transmittance of ocular media in living rabbit eyes. AB - PURPOSE: The purpose of this study was to measure the transmittance of electromagnetic radiation, particularly visible light, through the ocular media of living and whole rabbit eyes. Previous determinations have been carried out on excised cadaver eyes. METHODS: A specially designed fiberoptic probe (outer diameter, 0.9 mm) was placed in the vitreous in front of the retina using a microsurgical technique. In eight living albino rabbits (under general anesthesia), ocular transmittance was determined in the wavelength range 350 to 1100 nm using a reversed beam path (from vitreous to cornea). RESULTS: A maximum optical transmittance of 94% to 96% (standard deviation, 2%-3%) was found between 630 and 730 nm (reflection losses in the cornea-air interface excluded). In the blue portion of the spectrum, transmittance decreased rapidly for shorter wavelengths, and was 50% at 400 nm and less than 1% at 380 nm. In the infrared part of the spectrum, transmittance was close to 90% up to 900 nm but declined at longer wavelengths, coinciding with the absorption in pure water. Calibration recordings showed a 1% to 2% accuracy of the method. CONCLUSIONS: This experimental technique using an intraocular fiberoptic probe yields a high accuracy and indicates that light transmittance is very high in vivo and superior to that reported from cadaver eyes. PMID- 8440589 TI - Synthesis of lens capsule in long-term culture of human lens epithelial cells. AB - PURPOSE: This study examined the extent to which human lens epithelial (HLE) cells in tissue culture retain the potential for differentiation, expression of lens-specific marker proteins, and the synthesis of lens capsule, the major characteristics of lens epithelium in vivo. METHODS: Primary cultures of HLE cells were maintained for up to 450 days. Transmission and immunoelectron microscopy were used to study the thickness of the synthesized capsule and the formation of type IV collagen and laminin, two major protein components of the basement membrane of lens capsule in vivo. RESULTS: In a long-term HLE culture system, without subcloning, lens fiber differentiation and capsular synthesis were maintained over a period of 450 days. In these cultures, the cell sheet showed three distinct zones: (1) a central zone with tight monolayer; (2) a mild peripheral zone with irregularly aggregated multilayer; and (3) a peripheral zone with loose monolayer. The basement membrane-like material was synthesized in the central zone and lentoids, which serve as a model for fiber differentiation, developed primarily in the mid peripheral zone. No capsular material or lentoids were observed in the peripheral zone. The capsule-like material was 2 to 2.5 microns thick and showed the presence of type IV collagen and laminin, as detected by antibody reaction. CONCLUSION: This study demonstrates for the first time that HLE cells in long-term cultures synthesize a continuous sheet of capsule-like material. The findings also suggest that reformation of a tight cell to-cell relationship or generation of high cell density similar to that found in vivo may be an important factor for the synthesis of lens capsule. PMID- 8440590 TI - Noninvasive measurement of rat intraocular pressure with the Tono-Pen. AB - PURPOSE: The purpose of this study was to evaluate the Tono-Pen 2 tonometer for measuring intraocular pressure (IOP) in the living rat eye. METHODS: One eye from each of 20 adult, anesthetized brown Norway rats (group 1) was cannulated and simultaneously connected to a syringe and a pressure transducer with a chart recorder. We increased IOP from 15 to 45 mmHg in 5-mmHg increments and obtained 15 consecutive readings (ignoring instrument-generated averages) at each pressure increment with a Tono-Pen 2 tonometer. To test the tonopen's ability to measure unknown IOP, transducer pressures were varied randomly in 20 additional animals (group 2), and tonopen readings were obtained in masked fashion. RESULTS: Plotting the mean tonopen readings for each animal against transducer IOP produced a regression formula of y = 4.54 + 0.79x (r = 0.98). Mean group 2 tonopen values plotted against transducer IOP yielded a regression formula of y = 4.75 + 0.78x (r = 0.94). A method comparison analysis showed that the tonopen significantly overestimates pressures at low IOP (< or = 15 mmHg), and it significantly underestimates pressures at high IOP (> or = 30 mmHg). Using two way analysis of variance, it was determined that the group 2 data did not differ significantly from the group 1 data (P > or = 0.76). Because of this consistency, we generated a correction factor with 95% prediction intervals for Tono-Pen readings. CONCLUSIONS: The Tono-Pen 2 can be used reliably to measure IOP in the normal rat eye. PMID- 8440591 TI - The relationship between aqueous humor flow and anterior chamber protein concentration in rabbits. AB - PURPOSE: Protein concentration in the anterior chamber of noninflamed eyes is determined by three factors: the rate of protein entry into the aqueous humor (AH), the removal rate by bulk flow of AH, and the anterior chamber volume. On the basis of observations by previous investigators and the authors' computational modeling, it was hypothesized that a direct reciprocal relationship exists between aqueous flare and AH flow. This relationship was studied in pigmented rabbits, under several conditions, to determine the validity of the hypothesis that changes in aqueous flare intensity reflect variations in AH flow rate. METHODS: Aqueous flare and AH flow were measured in rabbits entrained to a 12 hr light: 12 hr dark cycle, starting at 6 AM, which subsequently was phase shifted 6 hr earlier to allow measurements over the light-to-dark transition period. AH flow rates were determined fluorophotometrically using the clearance method after corneal deposition of fluorescein. A Kowa FC1000 cell/flare meter was used to measure aqueous flare. Predictions of anterior chamber protein concentration were made using a computer model of plasma-derived protein diffusion into AH. The response to changes primarily of AH flow were evaluated by concurrently determining flare and flow before and after administration of intravenous acetazolamide. RESULTS: Aqueous flare decreased 40% during constant light and 47% over the light-dark transition in a parallel, monophasic manner. AH flow did not change significantly under either condition. In contrast, acetazolamide-induced changes in AH flow resulted in reciprocal changes in flare that could be simulated with the computer model through flow parameter changes alone. CONCLUSIONS: Anterior chamber protein concentration in rabbits appears to be modulated both by factors affecting AH flow and protein entry into the aqueous. Thus, in rabbits, changes in aqueous flare do not necessarily reflect AH flow changes. PMID- 8440592 TI - Pravastatin and simvastatin differently inhibit cholesterol biosynthesis in human lens. AB - PURPOSE: In the current study, the hypocholesterolemic drugs pravastatin and simvastatin were compared for their influence on cholesterol biosynthesis in the human lens. METHODS: For measurements of cholesterol and fatty acid synthesis rates, human lenses were incubated for 20 hr in the presence of [14C]-acetate, and pravastatin or simvastatin. Radiolabeled [14C]-cholesterol and [14C]-fatty acids were determined. To avoid the influence of individual differences, one lens from each donor was incubated without drug (control) and the other lens was incubated in the presence of drug. For each lens pair, the percentage inhibition of the cholesterol synthesis caused by the drug was calculated. Fatty acid synthesis was not influenced by the drugs. By comparing the fatty acid synthesis rate of the drug-incubated with the control lens of a pair, a predefined exclusion criterion was used to eliminate lens pairs in which the lenses had no comparable biosynthetic capacities. RESULTS: Using various concentrations of the drugs, a dose-response curve was constructed for the inhibition of the cholesterol synthesis. The IC50 values (drug concentration give 50% inhibition) were 0.5 mumol/l and 0.004 mumol/l for pravastatin and simvastatin, respectively. 3-Hydroxy-3-methylglutaryl coenzyme A reductase activity in microsomal membranes from human lens cortex was inhibited by simvastatin and pravastatin to the same extent. CONCLUSIONS: Under the conditions used in this study, cholesterol synthesis in human lenses is inhibited by simvastatin 100-fold more effectively than by pravastatin. This difference was likely due to differences in the intracellular exposure of the reductase to the drugs in intact human lenses. PMID- 8440593 TI - Retroperfusion studies of the aqueous outflow system. Part I: Evaluation of technique using N-ethyl maleimide. AB - PURPOSE: The goal of this study was to develop a new technique to deliver drugs or other agents to the lumen of the angular aqueous plexus/Schlemm's canal (AAP/SC) while bypassing the trabecular meshwork, thereby gaining insight into AAP/SC inner wall function. METHODS: The anterior chamber is held at a small negative pressure and fluid is allowed to flow retrograde from the limbal vessels, through the collector channels, and into the AAP/SC ("retroperfusion"). Facility measurements are combined with histologic and tracer studies in bovine eyes. RESULTS: (1) Retroperfusion with a saline solution does not alter facility or change outflow pathway morphology; (2) fluid is able to move retrograde from the scleral surface and enter the lumen of the AAP; and (3) retroperfusion with N ethyl maleimide causes a dose-dependent increase in washout rate and concomitant inner wall breaks. CONCLUSIONS: It is hypothesized that the observed increase in washout is due to leakage of extracellular materials through breaks in the inner wall. PMID- 8440594 TI - Foveal ganglion cell loss is size dependent in experimental glaucoma. AB - PURPOSE: The purpose of this study was to study the pattern of foveal ganglion cell loss in experimental glaucoma. METHODS: Retinal ganglion cell size and number in the foveal region of seven monkey eyes with experimental glaucoma was determined and compared to normal monkey eyes. Serial sections of macular retina were studied in two regions: the plateau of peak density of ganglion cells (800 1100 microns from the fovea), and within 500 microns of the foveal center. RESULTS: In normal eyes, cell densities were 37,900 +/- 2700 in the foveal plateau and 17,200 +/- 1800 cells/mm2 in the foveal center. There was selective loss of larger ganglion cells in glaucoma eyes. The degree of foveal ganglion cell loss was significantly correlated to the degree of nerve fiber loss in the temporal optic nerve of the same eye. CONCLUSIONS: Detection of early, central visual function loss in glaucoma could be enhanced by testing functions subserved by larger retinal ganglion cells. PMID- 8440595 TI - Distribution of epidermal growth factor receptors in rabbit lens epithelial cells. AB - PURPOSE: This study examined the growth-promoting effect of epidermal growth factor (EGF) on rabbit lens epithelial cells and the distribution of EGF receptors in these cells. METHODS: Rabbit lens epithelial cells were cultured in TC-199 medium containing 0.5% fetal bovine serum and EGF for 1 to 5 days, and the growth-promoting effects of EGF were calculated with absorbance of methylene blue staining method. EGF receptors in the cells were analyzed by Scatchard plots using 125I-EGF in serum-free culture. RESULTS: EGF, which enhanced the cell growth in a dose-dependent manner, was stimulatory at 0.1-100 ng/ml and maximal (328.2%) with 10 ng/ml on day 5. The cells had two different affinity receptors. The number and the dissociation constant of the low affinity receptors were 5.81 x 10(4)/cell and 1.488 nM, respectively, and those of the high affinity receptors were 1.53 x 10(4)/cell and 0.159 nM, respectively. CONCLUSION: EGF may contribute to the development of living lenses. PMID- 8440596 TI - Identification of transforming growth factor-beta expressed in cultured human retinal pigment epithelial cells. AB - PURPOSE: This study examined whether retinal pigment epithelial (RPE) cells have the capacity to express transforming growth factor-beta (TGF-beta). Also examined were TGF-beta isoform genes expressed in the RPE cells. METHODS: Complementary DNA (cDNA) was generated from polyA+ RNA extracted from human RPE cells in culture, and polymerase chain reaction (PCR) using degenerate and specific primers of the known TGF-beta isoforms was carried out by using the cDNAs as templates. Sequencing and Southern blot analysis of the PCR products, and Northern blot analysis were performed to identify which isoforms are expressed in RPE cells. RESULTS: PCR using degenerate primers showed that most of the amplified sequences were derived from TGF-beta 2, although TGF-beta 1 expression was shown by using specific primers. Northern blot analyses confirmed not only the expression of the TGF-beta gene, but also suggested that alternative splicing of TGF-beta mRNA in the RPE cells occurred. CONCLUSION: Cultured human RPE cells expressed TGF-beta 1 and beta 2 genes, whereas gene expression of TGF-beta 3 was not confirmed. Our data suggest that RPE cell are intraocular origin of TGF-beta production. PMID- 8440597 TI - Systemic hypertension produces pericyte changes in retinal capillaries. AB - PURPOSE: The purpose of this study was to examine retinal capillaries and their pericytes that previous research suggests to be contractile. A contractile role regulating capillary blood flow may be more apparent when the vasculature is subjected to the stress of systemic hypertension. METHODS: Using ultrastructural morphometry and the myosin subfragment-1 technique, retinal capillaries of normal and hypertensive rats were measured at three different time points, early, intermediate, and late (24, 44, and 68 wk). RESULTS: Hypertensive capillaries seemed to dilate at the early time point (P = 0.002), were constricted at the intermediate time point (P < 0.001), and did not redilate later. Wall thickness was enlarged at all times, pericyte coverage (the ratio of plasma membrane length in contact with the vascular circumference to the outer circumference of the endothelial tube) was greater at early and intermediate time points, and the total area of viable cytoplasm relative to the vessel wall area was increased at the intermediate time (all P < 0.001). Also, at the intermediate time, the circumferential coverage of the endothelial tube by actin filament bundles within pericytes and the actin area relative to the vessel wall area had increased (P < 0.001). CONCLUSIONS: These data indicate that the effects of systemic hypertension extend into the retinal capillary bed, causing pericyte change with actin increase and capillary constriction. They represent the first in vivo indirect evidence by morphologic criteria for pericyte contractility in retinal vascular disease. PMID- 8440598 TI - The effect of thrombin on actin filament and vinculin of corneal endothelial cells. AB - PURPOSE: The authors examined the effect of thrombin on confluent bovine corneal endothelial (BCE) cells in vitro, especially on cellular integrity and on the redistribution of F-actin and vinculin. METHODS: Immunofluorescent stainings against F-actin and vinculin were carried out on confluent BCE cells, and the effect of thrombin was evaluated. RESULTS: F-actin was distributed at the cytoplasmic peripheries of confluent BCE cells, forming dense peripheral bands (DPB), whereas vinculin was linearly located at the cell borders. Enzymatically active thrombin caused the loss of DPB and an increase of central microfilament bundles, associating the dissociation of vinculin-cell plaques and the formation of intercellular gaps. However, enzymatically inactive thrombin did not induce such changes. The thrombin effect was reversible and occurred in a concentration dependent manner. The pre-incubation of BCE cells with disrupting agents of microtubules, such as colchicine and demecolcine, or voltage-dependent Ca2+ channel blockers did not affect these thrombin-induced changes, whereas forskolin and energy blockers such as oligomycin AB and C and antimycin A inhibited these changes. CONCLUSIONS: Enzymatic-active thrombin affects the arrangement of the cytoskeletal structure of BCE cells and cell-substratum interaction and plays an important role in the re-integrity or repair processes of the monolayer of BCE cells. PMID- 8440599 TI - Hypoxia inhibits rhodopsin regeneration in the excised mouse eye. AB - PURPOSE: The goal of this study was to evaluate the effect of oxygen deprivation on rhodopsin regeneration in the excised mouse eye. METHODS: A new preparation for studying rhodopsin regeneration with a superfused excised albino mouse eye was developed. The preparation exhibits multiple regenerations after moderate bleaches (15%-20%) and is sensitive to the composition of the perfusate, allowing reversible testing of conditions. A variety of protocols were used to evaluate the effect of hypoxia. The major experiments varied the timing of the decreased oxygen relative to the illumination: Decreasing the oxygen (1) before the illumination, (2) immediately after the illumination, or (3) some time after the illumination, after half of the rhodopsin had regenerated. Elevated concentrations of extracellular glucose also were used for certain experiments. RESULTS: Regardless of protocol, at low levels of oxygen no rhodopsin regeneration was observed. The effects were reversible, however, and decreased oxygen for up to 3 hr did not diminish the ability of the eye to regenerate rhodopsin after restoration of the oxygen and a subsequent bleach. CONCLUSIONS: Low levels of oxygen eliminated rhodopsin regeneration in the excised eye. The effect could not be offset by high levels of glucose, illumination, or other conditions known to reduce the dependence of photoreceptors on aerobic respiration. PMID- 8440600 TI - Preproinsulin mRNA in the rat eye. AB - PURPOSE: The goal of this study was to extend the results of previous immunoassay, immunocytochemistry, and in situ hybridization studies showing the presence of insulin-related peptide in the rat retina by confirming the expression of insulin genes in the rat eye. METHODS: Total and poly(A)+ RNA were isolated from whole rat eyes, and separately from the retina, choroid, iris, lens, and vitreous. The poly(A)+ RNA was used for preparation of insulin-specific cDNA according to a coupled reverse transcription polymerase chain reaction (RT PCR) protocol under high stringency conditions. Southern transfers, restriction fragment analyses, and nucleotide sequencing were used to characterize and identify the amplified cDNA products. RESULTS: Amplified cDNA fragments of 329 +/ 6 base pairs (bp) were derived from whole rat eye and rat retina poly(A)+ RNA, but not from other regions of the eye. Southern blots probed with preproinsulin specific primer demonstrated homology with similar-sized cDNA from rat pancreas. Restriction digests with 10 restriction enzymes and direct nucleotide sequencing confirmed that the 329-bp cDNA was identical to the previously known coding sequence for rat pancreatic preproinsulin1 DNA. CONCLUSIONS: The identification of retinal preproinsulin1 mRNA was confirmed. This correlates with previous studies showing insulin immunoreactivity in rat eyes and in cultured retina, and verifies in situ hybridization evidence for the presence of insulin-related mRNA in retinal glial cells. PMID- 8440601 TI - Paracetamol hepatotoxicity. PMID- 8440602 TI - Shouldice hernia repair--a five year audit. AB - A retrospective clinical follow-up study of 96 inguinal hernia repairs by a general surgeon over a period of five and a half years using the same method of repair is discussed here with results of follow-up, post-operative complications and recurrence rates. The period of follow-up ranges from one month to five and a half years and no case of inguinal recurrence has so far been reported. One femoral recurrence was reported and its possible link to the Shouldice methodology is discussed. The average length of hospital stay has decreased over the five and a half year period. PMID- 8440603 TI - The use of recombinant human erythropoietin in end stage renal disease. AB - We treated 57 patients who suffered from end stage renal disease (ESRD) with recombinant human erythropoietin (EPO) for a mean period of 56 weeks. Patients were aged between 18 and 81 years. Forty three patients were on haemodialysis and 14 on continuous ambulatory peritoneal dialysis (CAPD). Despite regular transfusions, the mean haemoglobin prior to EPO therapy was 7.4 g/dl +/- 1.7. The target haemoglobin of 10 g/dl was reached at a mean of 12 weeks for the CAPD patients and at 14 weeks for the haemodialysis population. Patients were noted during the study to have a progressive rise in mean red cell volume, and this appeared to be related to their level of iron stores. The mean dose EPO used to reach the target haemoglobin was 8,700 u/week (125 u/kg/week) for the haemodialysis patients and 7,200 u/week (102 u/kg/week) for the CAPD patients. Three patients (7%) developed thrombosis of their A/V fistula. Hypertension was exacerbated in 28% of the patients. We conclude that EPO is a very effective but not inexpensive therapy for the anaemia of ESRD. PMID- 8440604 TI - Post traumatic intussusception in an adult. AB - Intussusception is a rare cause of intestinal obstruction in adults. When seen most cases have identifiable pathology. Intussusception following blunt abdominal trauma is extremely rare. This report presents a case of double jejuno-jejunal intussusception in a patient who sustained such an injury. There was no other intra-abdominal abnormality and manual reduction resulted in a complete recovery. The coincidental discovery of Q-fever may be etiologically relevant. PMID- 8440605 TI - Fine needle aspiration biopsy of lymph nodes and subcutaneous masses. AB - The results of fine needle aspiration biopsy of lymph nodes and subcutaneous masses in 169 patients and the technique used are discussed. Of the 169 cases 76 were classified as cytologically malignant, 52 as benign/inflammatory and 49 as inadequate. Neck masses were most commonly sampled. The overall diagnostic accuracy achieved was 75%. No false positive and 2 false negative cases were seen. The advantages and limitations of the procedure are discussed as well as some of the possible sources of error. PMID- 8440606 TI - Association of Chlamydia trachomatis with tubal infertility. AB - A study was undertaken to determine whether the positive correlation between Chlamydia trachomatis antibodies and tubal infertility, noted by workers in other countries, also applied to infertile women in Northern Ireland. Ninety-one infertile women and 106 fertile controls were tested for current cervical infection with C. trachomatis and for evidence of past chlamydial infection. The incidence of C. trachomatis infection of the cervix was 5.8% in the infertile group and 2.8% in the control group. The prevalence of C. trachomatis antibody was 22% in the infertile group and 18.9% in the control group. Previous termination of pregnancy, history of sexually transmitted disease and number of sexual partners were identified as risk factors for seropositivity and tubal disease. We concluded that it would be of value to screen women attending the infertility clinic for C. trachomatis infection of the cervix, and that testing these patients for chlamydia antibodies may also be useful in planning further investigation. PMID- 8440607 TI - Anaplastic carcinoma of the thyroid following radio-iodine therapy. AB - We describe a 79 year old lady who presented with a cytologically confirmed anaplastic carcinoma of the thyroid gland eleven years after administration of radio-iodine for thyrotoxicosis. This is, we believe, the first such occurrence documented in the Irish literature. PMID- 8440608 TI - Let the finger linger. AB - Retrorectal masses are rare and of insidious onset. We report a consecutive series of six such cases (males = 4, females = 2). The main presenting complaint was back pain and the most reliable physical sign was a palpable mass posteriorly on rectal examination (all cases). C T scan was the most radiologically informative investigation. Surgical intervention was undertaken using both anterior (trans-abdominal) and posterior (retrorectal) approaches. The majority of the masses excised were benign and all patients, to date, remain well. PMID- 8440609 TI - Assessment of cognitive function in patients with systemic lupus erythematosus. AB - The spectrum of central nervous system manifestations of systemic lupus erythematosus (SLE) is very broad and has been found to include subtle subclinical cognitive dysfunction which may be detected only by the lengthy process of detailed neuropsychological evaluation. This study reports the value of estimating premorbid intelligence as a simple yet effective means of screening for subclinical cognitive dysfunction. Twenty one female patients with clinically quiescent SLE underwent neuropsychological examination at entry to the study. In all patients, this examination included measurement of full-scale intelligence quotient (IQ), verbal and performance IQ as well as verbal and visual memories. In addition, premorbid intelligence was estimated using the Schonell graded word reading test. Nine patients (43%) gave a history of neuropsychiatric (NP) disease. No difference was identified between the results of the neuropsychological evaluation in these 9 patients and in either the other SLE patients or in age and sex matched control patients. Sixteen patients were re evaluated 1 year later. A comparison of measured full-scale IQ with the estimated premorbid intelligence identified a subgroup of 3 patients who demonstrated a significant reduction in intelligence. Unlike the other 13 patients, these 3 patients had multiple (3 or more) other features of cognitive impairment. PMID- 8440610 TI - Predictors of neck node control in radically irradiated squamous cell carcinoma of the oropharynx and laryngopharynx. AB - Cases of squamous cell carcinoma (171) of the oropharynx and laryngopharynx with clinically positive neck nodes, treated primarily by radiotherapy, were used for a multivariate analysis of the factors related to the regional outcome. All patients were staged according to the UICC-TNM (1982) classification. Lymph node size (P < 0.01), TNM nodal category (P < 0.05), and stage of the disease (P < 0.05) were significant in univariate analysis. Patient- and disease-related factors (age, sex, and histology) and treatment related factors (radiation dose (5000-6000 rads), radiation schedule, and concurrent chemotherapy) did not reach statistical significance. The stepwise logistic regression resulted in a final model with node size as the most important predictor of neck node control (P < 0.01). Patients with neck nodes up to 1 cm can receive radical radiotherapeutic management for treating the primary as well as nodal disease. PMID- 8440611 TI - Cisplatinum-epirubicin chemotherapy for advanced unresectable squamous cell carcinoma of the head and neck. AB - Twenty-seven patients with locally advanced unresectable squamous cell carcinoma of the head and neck were offered three courses of cisplatinum and epirubicin. The purpose of this study was to evaluate the effectiveness of this chemotherapy regimen. Subsequent therapy included surgery when feasible and/or radiation therapy. Eighteen patients completed three courses of chemotherapy. Three had a complete response and 14 a partial response. Nine patients refused chemotherapy before treatment was completed. Overall response rate was 63%. Among responding patients, the initial favorable response to chemotherapy was apparent after the first course of chemotherapy. A moderate degree of nausea, vomiting, anorexia, and alopecia were the most common toxicities. Leukopenia grade 3 according to ECOG criteria (WBC 1,000-2,000/mm3) was found in 8(44%) of the 18 patients completing treatment. There was no cardiac toxicity. This regimen appears to be an effective induction chemotherapy for advanced unresectable head and neck cancer with acceptable side effects. Subsequent therapy with surgery and/or radiation can give long-term local control of disease in some patients. In a selected group of patients with smaller tumors, this treatment should have a better response rate and a favorable effect on survival. Phase III studies using this regimen should be carried out. PMID- 8440612 TI - Oral cavity reconstruction: an objective assessment of function. AB - The prime objective of oral cavity reconstruction is restoration of function, which must be carefully studied while evaluating the success of any reconstructive endeavour. We devised a unique comprehensive test series for the purpose that is suitable for use in routine follow-ups, and capable of providing objective documentation. Functional assessment included evaluation of general health, food intake, oral competence, mastication, speech, swallowing, tongue mobility, and shoulder-neck function. Fifty patients who had surgery were analyzed and their functional scores compared with those of 10 normal volunteers. The extent of mandibular resection and the magnitude of soft tissue excision significantly affected overall scores of function. Oral competence, as reflected by the water holding test (WHT), was uniformly impaired in the 50 patients, and in dentate individuals, the quality of bolus provided good correlation with all other functional scores. Among reconstructive modalities employed here, the bi paddled pectoralis major flap produced the best overall scores. PMID- 8440613 TI - Clinical significance of laminin deposition and T-cell infiltration in oral cancer. AB - Biopsied specimens from 55 patients with squamous cell carcinoma (SCC) of the oral cavity were examined immunohistopathologically as to the clinical significance of basement membrane (BM) deposition and T-cell infiltration at the tumor-stromal border using monoclonal anti-laminin and anti-CD3 antibodies. According to the immunoreactivity, all specimens could be divided into three groups: group A, a continuous linear pattern of positive staining for BM around tumor nests; group B, an alteration of BM deposition around tumor nests with T cell infiltration into those tumor nests; and group C, an alteration of BM deposition around tumor nests without T cell infiltration into those tumor nests. These groups were correlated with clinical manifestations, such as tumor size, tumor regression rate with induction chemotherapy, and regional lymph node metastatic rate. In these groups, tumors classified as group C showed a trend toward resistance to chemotherapy and high metastatic characteristics. Tumors classified as group B, which showed the same alteration of BM deposition as a result of T cell infiltration into the tumor nests, showed a sufficient tumor regression rate with chemotherapy. The visualization of the staining for BM laminin and T cells in oral SCC appeared not only to increase our understanding of the biologic and clinical behavior of individual tumors, but could be a prognostic indicator. PMID- 8440614 TI - Combined approach for excision of cervical nerve tumors with dural extension. AB - Tumors of the cervical plexus are rare. Often these tumors are found on routine exam as asymptomatic masses. We present our experience in managing four patients with tumors with dural extension. Three of these lesions were neurilemomas and one was a meningioma. Symptoms and signs included weakness and hypoesthesia. Evaluation included complete neurologic examination with electromyography (EMG). Magnetic resonance imaging (MRI) was the best diagnostic tool to see tumor extent into the epidural and intradural space. Computed tomography (CT) or plain x-rays were used to evaluate the degree of destruction of the cervical spine. The surgical removal of these tumors was performed by a two-team approach. A posterior laminectomy was combined with an anterior neck exploration. Follow-up shows persistent upper extremity weakness in two patients, hypesthesia in three patients, and anesthesia of the anterior chest wall in two patients. Patients with these lesions should be informed of the potential neurologic consequences of removal. PMID- 8440616 TI - Retropharyngeal leiomyoma: case report and review of the literature. AB - An 8-year-old girl was initially seen with dyspnea, drooling of secretions, and loss of weight. A large mass was seen protruding through the posterior pharyngeal wall, which was found to be a leiomyoma after excision. No previous case report exists of a retropharyngeal leiomyoma. PMID- 8440615 TI - Surgical strategies for differentiated carcinoma of the thyroid isthmus. AB - The postoperative outcome (including clinicopathologic features) in 19 patients with differentiated thyroid cancer of the isthmus was investigated to develop more appropriate surgical strategies for these lesions. The extent of thyroidectomy, including neck dissection, tumor size, nodal involvement, and other clinical features were evaluated. The incidence of intraglandular dissemination was about 16% in all patients. Analysis of regional node metastatic distribution revealed no definite metastatic pattern. In addition, there was no apparent correlation between tumor size and nodal involvement. Two of the six patients who underwent total thyroidectomy suffered permanent postoperative hypoparathyroidism. It is thus recommended that isthmusectomy, including an adequate edge of surrounding normal thyroid tissues of each lobe and modified or limited neck dissection when cervical nodes are palpably enlarged, is sufficient as an appropriate primary surgical procedure for differentiated carcinoma of the thyroid isthmus. PMID- 8440617 TI - Vascular considerations in approaches to the deep midface. PMID- 8440618 TI - Neonatal vocal cord paralysis. AB - The consultants agree that surgery is a common cause of unilateral vocal cord paralysis in neonates. In the absence of a history of surgery, they would evaluate a neonate for cardiovascular or central nervous system anomalies. None believes a relationship between laryngomalacia and vocal cord paralysis exists. But there is disagreement regarding the additional steps required to evaluate this child. The recommendations include endoscopy under general anesthesia with assessment of cricoarytenoid mobility, evaluation for other congenital anomalies, and observation of laryngeal dynamics (Dr. Benjamin), neurologic examination (Dr. Bailey), and no further testing (Dr. Gray). Laryngeal EMG in an infant is not an established technique and none of the consultants routinely performs this test. However, EMGs are part of the research protocol for one physician (Dr. Gray). The consensus is that aspiration is unlikely to be a problem in this case. However, if aspiration does occur, all would recommend conservative treatment. Feedings should be thickened and anti-reflux precautions taken. None was convinced that severe aspiration would be a problem. However, given the need for more aggressive treatment, the considerations would include collagen or Teflon injections or a tracheotomy (Dr. Gray) or a Nissen fundoplication, nasogastric tube feedings, or a gastrostomy (Dr. Bailey). Only one consultant would defer further treatment (Dr. Benjamin). The prognosis is generally good. Two consultants (Drs. Benjamin and Bailey) would follow a child with vocal cord paralysis by periodically repeating a laryngoscopic examination. A reinnervation procedure would be considered by one consultant at the age of 3 if the voice remains weak (Dr. Gray). PMID- 8440619 TI - Twice-a-day radiotherapy for squamous cell carcinoma of the head and neck: the University of Florida experience. AB - Between March 1978 and March 1989, 419 patients with 439 moderately advanced or advanced primary squamous cell carcinomas of the head and neck received treatment with curative intent with twice-a-day radiotherapy (120 cGy per fraction with a 4 to 6-hour interfraction interval). Seventy-nine percent of the patients had AJCC stage III or stage IV cancers. The primary site in most patients was the oropharynx, hypopharynx, or larynx. All patients received radiotherapy alone to the primary site, with or without planned neck dissection after radiotherapy. Surgery at the primary site was reserved for salvage of radiotherapy failures. No patient received chemotherapy as part of the initial treatment plan. Total doses were 7440 cGy to 7920 cGy in the majority of patients. In 54 patients with oropharyngeal lesions, an interstitial implant was used to add a 1,000- to 1,500 cGy boost after the basic dose. Local control results were compared on a site-by site and stage-by-stage basis with the results of continuous-course, once-a-day radiotherapy at the University of Florida; the control results were the same as or better than after once-a-day radiotherapy for each site and stage (T2 to T4). Severe complications of radiotherapy occurred in 4% of patients and correlated with tumor dose, T stage, and disease site (oropharynx or larynx/hypopharynx). The addition of a neck dissection 4 to 6 weeks after radiotherapy of patients with advanced-stage neck disease was accomplished with an acceptable rate of morbidity and significantly improved the rate of control of neck metastases compared with radiotherapy alone. PMID- 8440620 TI - Reconstruction of extensive defects of the cranium using free-tissue transfer. AB - Fourteen patients with large tissue deficits in the calvarium and orbits were reconstructed using microvascular free-tissue transfer (15 flaps). The etiology of these defects was skin neoplasms (seven), osteomyelitis (four), burn (two), and trauma (one). The free flaps used were the latissimus dorsi muscle flap with a split-thickness skin graft (seven), latissimus dorsi myocutaneous flap (two), rectus abdominis myocutaneous flap (three), radial forearm fasciocutaneous flap (two), and split-iliac crest flap (one). There was one postoperative death, one flap failure, two recurrences of neoplasm, and one loss of bone grafts and flap from infection. The free flaps can offer good results in patients undergoing wide resection in the cranium and orbits providing immediate repair with acceptable cosmetic result, minimized morbidity, and short hospitalization. However, immediate reconstruction following tumor resection carries a danger of positive margins discovered on permanent histologic sections or the difficulty in detecting recurrence underneath a bulky free flap. PMID- 8440621 TI - Comments on radiation processing of food. PMID- 8440622 TI - Pregnancy in the workplace. PMID- 8440623 TI - ECG of the month. PMID- 8440624 TI - A stranger in paradise. PMID- 8440625 TI - The veterinary medical/health sciences library as a continuing education opportunity for veterinarians. PMID- 8440626 TI - The unlicensed practice of veterinary medicine. PMID- 8440627 TI - Use of isotretinoin and etretinate for the treatment of benign cutaneous neoplasia and cutaneous lymphoma in dogs. AB - The purpose of this study was to evaluate the synthetic retinoids isotretinoin and etretinate to treat dogs with intracutaneous cornifying epitheliomas (ICE), other benign skin neoplasias, and cutaneous lymphoma. Twenty-four dogs were used. All tumors were diagnosed by histologic examination. Ten dogs with multiple (at least 5) benign skin tumors (7 with ICE, 1 each with inverted papillomas, sebaceous adenomas and epidermal cysts) were treated with isotretinoin (n = 7) and/or etretinate (n = 5). Twelve dogs with cutaneous lymphoma were treated with isotretinoin, and 2 dogs with cutaneous lymphoma were initially treated with etretinate. Successful treatment with isotretinoin was achieved in 1 dog with ICE, 1 with inverted papillomas, and 1 with epidermal cysts. Partial improvement with isotretinoin was seen in 2 dogs with ICE. Successful treatment was achieved with etretinate in 4 dogs with ICE (Norwegian Elkhound was the predominant breed with ICE). Remission was achieved in 6 of the 14 dogs with cutaneous lymphoma. Adverse effects developed in 7 of the 24 dogs, so treatment was stopped in 2 dogs. PMID- 8440628 TI - Efficacy of microcrystalline desoxycorticosterone pivalate for treatment of hypoadrenocorticism in dogs. DOCP Clinical Study Group. AB - The efficacy of microcrystalline desoxycorticosterone pivalate (DOCP) therapy was evaluated in 60 dogs with hypoadrenocorticism. Fifty-one of the dogs were being treated with either DOCP or fludrocortisone acetate prior to entering the study. The disease had been recently diagnosed in 9 dogs that were not under maintenance treatment prior to entering the study. Desoxycorticosterone pivalate (2.2 mg/kg of body weight, IM) was administered on days 0, 25, and 50. Physical examination was performed, and blood samples were obtained for serum biochemical analysis (Na+, K+, and BUN concentrations) on days 0, 14, 25, 39, 50, 64, and 75. On day 75 of the study, a final physical examination was performed and the course of treatment was evaluated. Sixty-eight percent (41/60) of the dogs had normal physical findings on day 0 vs 87% (52/60) on day 75. Mean (+/- SD) body weight increased from 24.8 +/- 12.7 kg on day 0 to 26.2 +/- 13.7 kg on day 75. Mean serum Na+ (137.7 +/- 8.5 mEq/L) and K+ (5.6 1.0 mEq/L) concentrations and Na(+) to-K+ ratio (25.4 +/- 5.0:1) were outside normal reference limits on day 0. By day 75, serum Na+ (144.3 +/- 4.8 mEq/L) and K+ (4.9 +/- 0.8 mEq/L) concentrations and Na(+)-to-K+ ratio (30.4 +/- 5.1:1) were normal and were significantly (P < 0.01) improved, compared with the corresponding values on day 0. Of the 60 dogs, 58 (97%) regained the loss in body weight, appetite, and muscular strength while given DOCP; once achieved, these improvements were maintained. These 58 dogs did not vomit or have diarrhea, common problems in dogs with hypoadrenocorticism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8440629 TI - Accuracy of references and quotations in veterinary journals. AB - The accuracy of references and quotations used to substantiate statements of fact in articles published in 6 frequently cited veterinary journals was examined. Three hundred references were randomly selected, and the accuracy of each citation was examined. A subset of 100 references was examined for quotational accuracy; ie, the accuracy with which authors represented the work or assertions of the author being cited. Of the 300 references selected, 295 were located, and 125 major errors were found in 88 (29.8%) of them. Sixty-seven (53.6%) major errors were found involving authors, 12 (9.6%) involved the article title, 14 (11.2%) involved the book or journal title, and 32 (25.6%) involved the volume number, date, or page numbers. Sixty-eight minor errors were detected. The accuracy of 111 quotations from 95 citations in 65 articles was examined. Nine quotations were technical and not classified, 86 (84.3%) were classified as correct, 2 (1.9%) contained minor misquotations, and 14 (13.7%) contained major misquotations. We concluded that misquotations and errors in citations occur frequently in veterinary journals, but at a rate similar to that reported for other biomedical journals. PMID- 8440630 TI - Serum biochemical changes in dogs competing in a long-distance sled race. AB - Fifty-five blood samples were collected from 28 dogs competing in the 1991 Yukon Quest International Sled-Dog Race to examine race-induced changes in serum biochemical values. Blood was collected after a 36-hour mandatory rest at the midpoint of the race, and again at 2 subsequent checkpoints. The mean speed of dogs between checkpoints was approximately 4.5 mph. There were no significant increases in PCV, or in serum total protein, sodium, or creatinine concentrations during the race. Mean serum potassium concentration decreased significantly (P < 0.05) from 4.8 +/- 0.4 to 4.4 +/- 0.3 to 3.9 +/- 0.3 mEq/L, as did the serum triglyceride concentration (138 +/- 52, 88 +/- 25, 81 +/- 16 mg/dl). Plasma cortisol concentration did not change significantly. Increases in the mean serum activity of creatine kinase (167, 420, 344 U/L), and aspartate aminotransferase (55, 79, 62 U/L) during the race were significant (P < 0.05). Participation in a long-distance sled race was associated with mild changes in routinely measured serum biochemical values in dogs. PMID- 8440631 TI - Chronic selenosis in horses fed locally produced alfalfa hay. AB - Chronic selenosis (alkali disease) was diagnosed in horses of western Iowa, a region associated with marginal to adequate soil selenium. Two locally produced alfalfa hays (Medicago sativa L) were identified as the primary source. Difficulty in selecting diagnostic specimens to evaluate potential chronic selenosis cases is complicated by the wide range of tissue concentrations reported in previous cases, conflicting correlation of sample selenium concentrations in the literature, and different recommendations on specimen selection and diagnostic value. These problems arise form the similarity in clinical signs for mild and severe chronic selenosis cases, and inability to establish the disease time course. Therefore, collection of multiple samples to confirm high selenium concentration in various tissues and identify selenium sources is recommended. Value of samples believed to reflect historical exposure vs current status may be questionable. Interpretation of results by practitioners and diagnosticians should consider selenium exposure level and duration, antagonistic or ameliorating factors, and postexposure excretion. PMID- 8440632 TI - Diaphragmatic hernia in a llama. AB - A 7-year-old castrated male llama was admitted for evaluation of mild colic. Exploratory celiotomy revealed a diaphragmatic hernia that was entrapping the proximal portion of the ascending colon. The hernia was reduced, and the devitalized ileum, cecum, and 45 cm of the proximal portion of the ascending colon were resected. Surgical repair of the defect in the diaphragm could not be accomplished from the ventral celiotomy, and the owners declined definitive repair via left thoracotomy. The llama recovered and did well until 9 months after surgery, when the hernia recurred. Necropsy revealed a defect, with characteristics consistent with a congenital origin, in the dorsal part of the left hemidiaphragm. On the basis of the findings in this llama, repair of such defects is strongly advocated. PMID- 8440634 TI - Diffuse cutaneous leishmaniasis in a cat. AB - An adult long-haired domestic cat native to South Texas developed signs consistent with diffuse cutaneous leishmaniasis. Cutaneous leishmaniasis, caused by Leishmania mexicana, was initially diagnosed from lesions confined to the left ear. A radical pinnectomy was done and the cat was returned to its owner. Two years later, lesions developed at the stump, and lesions later developed on the cat's muzzle and nasal mucosa. All of the lesions contained numerous L mexicana amastigotes. Several treatment regimens were attempted, but without evidence of resolution. The cat was tested multiple times for evidence of impaired immunologic competence and was found to be normal. The cat failed to respond to Leishmania antigen given interdermally (Montenegro test) on several occasions. On one occasion, however, there was partial regression of the lesions following the Montenegro test. Cats in areas endemic for cutaneous leishmaniasis (South Texas) may serve as sentinels for the agent. The epidemiology of the infection in this area is largely unknown, as is the importance of cats in the spread of disease. PMID- 8440633 TI - Ventral dermatitis and vasculitis in a calf with bovine leukocyte adhesion deficiency. AB - Dermatitis and vasculitis of the skin covering the sternum of a calf with bovine leukocyte adhesion deficiency was observed. The calf had been conceived through artificial insemination, delivered by cesarean section, and placed in a gnotobiotic isolator. Dermatitis was noticed at 54 days of age and was not responsive to antibiotic or ivermectin treatment. Proteus sp, Enterobacter sp, and Candida tropicalis were isolated from skin specimens. The lesion was characterized by lymphoplasmacytic and histiocytic inflammation with vasculitis and thrombosis. PMID- 8440635 TI - Uterine tear without a corresponding placental lesion in a mare. AB - A 3-cm full-thickness tear near the tip of the previously gravid uterine horn of a 12-year-old Thoroughbred mare was diagnosed at surgery. The mare had delivered a foal with veterinary assistance 2 days prior to surgery. The mare subsequently developed muscle tremors, anorexia, and signs of depression. Physical examination revealed pyrexia, extended capillary refill time, muscle fasciculations, and fewer-than-normal borborygmi. Abnormalities of the uterus or vagina were not detected by palpation per rectum or per vagina. The chorioallantois underlying the area of the tear was intact. We propose that the uterine tear was caused by pressure created by the foal's stifle against the maternal pelvis or by blunt forces caused by the foal's foot, sufficient to tear the uterus, but not the chorioallantois. PMID- 8440636 TI - Bilateral distal fibular growth abnormalities in a dog. AB - A 6-month-old Shetland Sheepdog was examined because of a valgus deformity of the left hind limb. Six weeks earlier, the dog had developed a fracture of the distal portion of the right fibula, which was successfully treated by use of external coaptation. Radiography revealed valgus deformity centered at the left distal tibial and fibular physes. Radiographically, the left fibula was 1.5 cm shorter than the left tibia, and the right fibula was 1.3 cm shorter than the right tibia. A distal tibial closing wedge ostectomy was performed to correct the left hind limb angular deformity. The angular deformity was believed to have developed because of abnormal growth of the left distal fibular physis. It is likely, considering the displacement of the right fibular head, that the dog also had premature closure of its right distal fibular physis. The fracture of the right fibula may have prevented development of an angular deformity of the right hind limb. PMID- 8440637 TI - Identification of Histoplasma capsulatum organisms in the pleural and peritoneal effusions of a dog. AB - Histoplasma capsulatum organisms were identified by cytologic evaluation in the thoracic and abdominal effusions of a 5-year-old sexually intact male Cocker Spaniel that was referred because of anorexia and lethargy. Treatment with amphotericin B and ketoconazole was instituted. The dog developed respiratory arrest, a complication of the disseminated disease, and died. Necropsy findings included pleural effusion, hepatomegaly, and enlarged tracheobronchial, hilar, mediastinal, and mesenteric lymph nodes. Granulomas containing periodic acid Schiff (PAS)-positive yeast-like organisms identified as H capsulatum were seen in the lungs, liver, and lymph nodes. The lymphatic vessels were dilated, and fibrosis of the portal and periportal regions of the liver was noticed. Identification of Histoplasma organisms by cytologic examination of pleural and abdominal effusions is a rare laboratory finding and can provide a minimally invasive and inexpensive definitive diagnosis of histoplasmosis. PMID- 8440638 TI - Lip fibromas associated with retrovirus-like particles in angel fish. AB - Fibromas were observed on the lips of adult female and juvenile angel fish (Pterophyllum scalare) from 3 Florida farm populations. Tumor prevalence in each population was < 1%. Affected fish were clinically normal except for those with large tumors, which had weight loss caused by physical obstruction of food intake. Fibromas originated as elevated masses from the mucocutaneous junction near the midline of the upper and/or lower lips. Characteristic features included dense fibrous stroma covered by thickened, stratified squamous epithelium, numerous intraneoplastic teeth, and scattered foci of stromal inflammation. Electron microscopy revealed intracytoplasmic type-A retrovirus-like particles in stromal cells from all tumors. Attempts to transmit fibromas, using a cell-free tumor ultrafiltrate, were unsuccessful. The relationship of the intraneoplastic viral particles to the development of lip fibromas in angel fish is uncertain. PMID- 8440639 TI - Upward fixation of the patella in cattle: 38 cases (1984-1990). AB - Case records of cattle admitted to 2 university veterinary hospitals during 6 years were evaluated to determine the age, breed, sex, and treatment of cattle with upward fixation of the patella. Affected cattle were compared with those from the respective hospital populations of cattle admitted during the same time. Of 38 cattle with upward fixation of the patella, 34 were treated surgically. Follow-up evaluation was obtained from owners of 28 of the treated cattle. Surgery was successful in eliminating all clinical signs in 25 of the 28 cattle. There was an increased risk of upward fixation of the patella associated with Brahman and Brahman-type cattle, compared with non-Brahman cattle. PMID- 8440640 TI - Surface-induced hypothermia in dogs: 19 cases (1987-1989). AB - Surface-induced hypothermia is used to protect tissues from ischemic events during surgery. In a review of 19 clinical cases in dogs, the technique was used to enable intracardiac surgery (4 dogs) and to facilitate removal of extensive thoracic or abdominal masses (15 dogs). For 16 dogs (84%), anesthesia was induced with an opioid/benzodiazepine combination and maintained with a balanced technique by use of an opioid, a neuromuscular blocking agent, and isoflurane in oxygen. Dogs were cooled in an ice bath to a mean esophageal temperature of 27.8 +/- 1.4 C. Mean anesthesia time was 4.04 +/- 1.37 hours. Hypothermic-induced adverse effects, such as increased blood viscosity, increased myocardial irritability, and shivering, were managed by hemodilution, manipulation of acid base balance, and administration of opioid and neuromuscular blocking agents. Complications requiring treatment included severe hypotension (74%), arrhythmias (47%), hypoxemia (42%), and acidemia (58%). Six dogs (32%) went into cardiac arrest and all were successfully resuscitated once the surgical procedure was completed. One dog was euthanatized during surgery, another died after surgery, and the 17 remaining dogs (90%) were discharged from the hospital to their owners. The technique appears beneficial in selected cases to decrease the morbidity and mortality associated with the risk of prolonged ischemia and life threatening hemorrhage. PMID- 8440641 TI - Uterine tube disease in cattle. PMID- 8440642 TI - What is your diagnosis? Splenomegaly and hepatomegaly in a macaw caused by chlamydiosis. PMID- 8440643 TI - What is your diagnosis? Diffuse nodular interstitial-to-alveolar pattern throughout the lungs. PMID- 8440644 TI - Herbage allowance x yearling heifer phenotype interactions for the growth of Brahman-Hereford F1 first-calf females grazing humid pasture and semiarid rangeland. AB - Growth data were collected over 4 yr from 349 Brahman-Hereford F1, first-calf, lactating females that had been allotted as weanlings to either semiarid extensive rangeland (Uvalde) or humid improved Bermudagrass pasture (Overton) and to one of four herbage allowance levels at each location as yearlings. Heifers were wintered according to systems in local practice and maintained on allotted forage levels both as yearlings and during their first lactation. Heifers were bred to Braford bulls to calve as 2-yr-olds in January to March. Herbage allowance (400 to 2,800 kg of DM/100 kg BW at Uvalde and 80 to 460 kg of DM/100 kg BW at Overton) was maintained by adjusting stocking density monthly from April to weaning (October). Herbage allowance and yearling heifer hook height, condition score, or weight (taken on April 15) were continuous independent variables in regression analyses. Final heifer weight, height, and condition responses to increased herbage allowances were related to yearling phenotypes differently (P < .01) for the two locations. At Uvalde, yearling condition score interactions were especially important in that heifers that had more condition (especially those > 5 for 1 to 10 with 10 = fattest) as yearlings retained more (P < .05) weight and condition and grew more (P < .05) in height than did those of lower yearling condition. These females also responded to increased herbage allowance by gaining advantage (P < .05) in these variables, whereas those of lower yearling condition made smaller advances. At Overton, yearling condition played little role in subsequent growth. The yearling variable that had the greatest interactive effect was height. Shorter yearling heifers (< 123 cm) responded (P < .07) to increased herbage allowance so that they had greater final condition and grew more rapidly in height than those taller as yearlings. PMID- 8440645 TI - Environmental effects on neonatal mortality of beef calves. AB - Calving records from 1969 to 1989 from the Roman L. Hruska U.S. Meat Animal Research Center were used to investigate how climatic conditions, in addition to dystocia, age of dam, size of calf, and sex affect calf survival from birth to 1 wk of age. Data were analyzed separately for cows calving with (n = 11,094) or without (n = 72,187) dystocia. Neonatal mortality was described by a logit model and parameters were estimated by maximum-likelihood procedures. Calves born to cows with dystocia were five times as likely to die neonatally than calves born without assistance. Of all calves that died, 43.6% were born with difficulty. Of these calves, survival was lowest for those that were small relative to their genetic group, sex, and age of dam. Large calves had markedly increased mortality only when born to 2-yr-old dams. Average ambient temperature and precipitation on day of calving affected survival nonlinearly and the magnitude of the effect depended on age of dam, sex and size of calf, and dystocia incidence. Calves born to 2-yr-old cows were more susceptible to severe weather conditions than calves born to older cows. The negative effect of precipitation on survival increased with decreasing temperature. PMID- 8440646 TI - Investigating optimal bull:heifer ratios required for estrus-synchronized heifers. AB - The objectives of this study were to determine 1) the effect of bull:heifer ratio on reproductive performance and associated costs and return on heifers in synchronized estrus and 2) the effect of estrus synchronization on reproductive performance and economic variables, in a multiple-sire, pasture breeding situation. Eight hundred yearling beef heifers and 28 mature, sexually experienced beef bulls were allotted to four treatments (two replicates per treatment) at bull:heifer ratios of 2 per 100 (1:50; Treatment 1), 2 per 100 (1:50; Treatment 2), 4 per 100 (1:25; Treatment 3), and 6 per 100 (1:16; Treatment 4). Treatment 1 (control) used nonsynchronized heifers, whereas heifers in Treatments 2, 3, and 4 were synchronized using the 33-d melengestrol acetate (MGA)-prostaglandin F2 alpha (PGF2 alpha) program. Pregnancy results after a 28-d breeding season indicate that there may be a limit to how many estrus synchronized heifers bulls can impregnate. Treatment 2 showed a 6% decrease (P < .10) in pregnancy rate (77%) compared with Treatment 3 (83%), indicating that the bulls probably were not able to service all the synchronized heifers. Treatments 3 and 4 had similar pregnancy rates (83 and 84%, respectively). Treatment 4 had a 3-d advantage (P < .01) over Treatment 3 in average day of conception. However, based on economic analysis, Treatment 3 exhibited greater returns. Estrus synchronization failed to provide any advantage in pregnancy rate or day of conception. For unknown reasons, the control, nonsynchronized heifers cycled and conceived as if they were synchronized.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8440647 TI - Effect of oxygen and neostigmine on stillbirth and pig viability. AB - In this experiment, 98 multiparous Yorkshire sows blocked on farrowing date were randomly assigned to four treatments in a 2 x 2 factorial arrangement. Oxygen inhalation (6 L/min) by the sow was tested in an effort to reduce stillbirth rate and improve pig viability. This study also tested the effect of increasing uterine contractions using neostigmine (5 mg) to determine whether simultaneous administration of oxygen to the sow could improve the inconsistent response of stillbirth rate to neostigmine. Pig viability was assessed using viability scoring and blood gas analysis of samples obtained from the suborbital sinus immediately after birth. The farrowings averaged 12.2 pigs/litter, 7.8% stillbirths, and 3.5% low viability (viability score < or = 6) pigs. Treatment had no effect on stillbirth rate or pig viability. Oxygen treatment increased pO2 (P = .0002), increased pCO2 (P = .02), and decreased pH (P = .02) in sow venous blood sampled after the birth of the last pig, but it had no effect on pig venous blood gases. Neostigmine treatment had no effect on either sow or pig venous blood gases. Oxygen treatment doubled the length of the first birth interval after the start of treatment (P = .003) but had no effect on remaining birth intervals. Neostigmine had no effect on birth interval. It is suggested that the effect of oxygen on birth interval is the reason for the lack of improvement in stillbirth rate. PMID- 8440648 TI - Yearling bulls shorten the duration of postpartum anestrus in beef cows to the same extent as do mature bulls. AB - The objective of this study was to determine whether yearling bulls, when pastured with cows, reduced the duration of postpartum anestrus to the same extent as did mature bulls. This experiment was conducted over a 3-yr period. Cows were stratified by parity group to achieve 37% 2-yr-old and 63% mature (> 2 yr-old) cows within each treatment group (approximately 50 cows per treatment per year). Cows were assigned in the order in which they calved to one of three treatment groups: 1) isolated from bulls (NBE; n = 158); 2) exposed to mature bulls that were > 3 yr of age (MBE; n = 154); or 3) exposed to bulls that were 1 yr of age (YBE; n = 152). Beginning the 2nd wk after calving, cows were pastured with either sterile bulls that were 1 yr (YBE) or > 3 yr of age (MBE) (three bulls per treatment group). Blood samples were collected twice weekly from late March until mid-July each year. Cows with serum concentrations of progesterone > 1 ng/mL for two consecutive sampling periods were assumed to have initiated estrous cycles after calving. Duration of postpartum anestrus in cows exposed to yearling bulls (YBE = 61.8 +/- 1.8 d) did not differ (P > .10) from duration of postpartum anestrus in cows exposed to mature bulls (MBE = 59.5 +/- 1.7 d). Duration of postpartum anestrus was shorter (P < .01) for cows exposed to bulls (MBE+YBE = 61.0 +/- 1.7 d) than for cows isolated from bulls (NBE = 72.3 +/- 1.8 d).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8440649 TI - Simulated effects of culling ewes for age and failure to conceive on biological efficiency of an annual lambing production system. AB - A deterministic computer simulation model was used to estimate the effects of different culling strategies for nonconception and age on the biological efficiency of an annual lambing system. Interaction among culling strategy and genotype for system efficiency was estimated by also varying ewe genetic potentials for fertility, precocity of fertility, and litter size. Biological efficiency was defined as grams of empty body weight equivalent value of market lamb, cull ewe, and wool output per kilogram input of TDN. Pure breeding with random selection of intraflock replacement ewe lambs was assumed. Sheep were fed to maintain normal weight. Maximum allowable ewe age (i.e., time at culling for age) was varied from 2 to 10 yr. The four strategies of culling for nonconception that were simulated ranged from no removal for nonconception to removal of all nonpregnant ewes 15 wk after exposure. During calculation of lamb empty body weight equivalent, relative values per kilogram of output for market lambs, cull ewes, and clean wool were assumed to be 1 to .33 to 2.04 for most simulation runs. In addition, relative value of cull ewes was varied to .01, .16, .50, or .99 for some simulations. The effect of strategy for removal of nonconceiving ewes on system efficiency depended on maximum ewe age and genotype. In general, if relative value per kilogram of cull ewes to market lambs was < or = .50, ewes should be allowed to produce through 4 or 5 yr of age and then be salvaged. Unless salvage value of culled ewes approaches that of market lambs, ewe lambs should not be culled for failure to conceive. PMID- 8440650 TI - Performance of hair breeds and prolific wool breeds of sheep in southern Illinois: effect of breed of service sire on lamb production of Suffolk and Targhee ewes. AB - The effects of year, age of ewe, sex of lamb, breed of ewe, and breed of service ram on fertility, prolificacy, lamb survival, lamb weaning weight, and ewe productivity of Suffolk and Targhee ewes mated to Finnsheep, Combo-6, Booroola Merino, St. Croix, and Barbados rams were estimated. Matings were in four consecutive years using three rams per breed of service ram each year, with a total of 758 ewe-year observations. There was a significant effect of year on fertility, prolificacy, and ewe productivity. Two- and three-year-old ewes had lowest (P < .05) fertility rates, whereas 3-, 4-, and 5(+)-yr-old ewes had higher (P < .01) prolificacy and ewe productivity than 2-yr-old ewes. Ram lambs were .9 kg heavier (P < .01) at weaning than were ewe lambs. Suffolk ewes gave birth to .13 more (P < .05) lambs per ewe lambing, and their lambs were 1.4 kg heavier (P < .01) than lambs from Targhee ewes. Ewes mated to St. Croix and Barbados rams had higher (P < .10) fertility rates than ewes mated to Finnsheep rams. Lambs sired by Barbados, Finnsheep, and St. Croix rams had higher (P < .05) survival rates to weaning than lambs sired by Booroola Merino rams. The heaviest (P < .01) lambs at weaning were those sired by Finnsheep and Combo-6 rams. Ewes mated to hair-breed rams had greater (P < .05) performance for the fitness traits of fertility and lamb survival but lower (P < .01) lamb weaning weights than ewes mated to wool-breed rams.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8440651 TI - Genotype x environment interactions in preweaning traits of purebred and reciprocal cross Angus and Brahman calves on common bermudagrass and endophyte infected tall fescue pastures. AB - Preweaning data on 486 Angus, Brahman, and reciprocal cross calves (AB, BA) managed on common bermudagrass or endophyte-infected tall fescue were used to evaluate the interactions of forage type and sex of calf with direct effects, individual heterosis, and maternal effects. Calves were spring-born in 1988, 1989, 1990, and 1991 to five sires of each breed. Male calves were castrated at birth, and calves were not creep-fed. Average values of heterosis for birth weight, 205-d weight, weaning hip height, and weaning weight:height ratio (WT/HT) were important (P < .01) and consistent across forage environment. Heterosis for birth weight was larger in bull calves than in heifer calves (P < .05), whereas heterosis for other preweaning traits were consistent across sex of calf. Average maternal effects for WT/HT (P < .10) were important and consistent across forage environment. Maternal effects for birth weight were larger with bull calves than with heifer calves (P < .01). Maternal effects for weaning hip height favored the Angus dam managed on bermudagrass (P < .05) but not managed on fescue. A similar but nonsignificant trend occurred in maternal effects for 205-d weight. Direct effects for birth weight were larger in bull calves than in heifer calves (P < .01). Direct effects for weaning height were larger in calves managed on bermudagrass than in calves managed on tall fescue (P < .07). A similar but nonsignificant trend was evident in direct effects for 205-d weight. Direct effects for WT/HT were relatively small and unimportant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8440652 TI - Divergent selection for postweaning feed conversion in Angus beef cattle: III. Linear body measurements of progeny. AB - Postweaning performance data were obtained on 401 group-fed, purebred Angus calves from 24 selected sires (12 high- and 12 low-feed-conversion sires) from 1983 through 1986 at the Northwestern Branch of the Ohio Agricultural Research and Development Center. Body measurements of progeny were taken from 1983 through 1986 for hip height and backfat, whereas others, except chest measurements (depth and width) that were available only in 1985, were taken from 183 progeny born in 1985 and 1986. The objective of this portion of the study was to determine whether differences in linear body measurements exist between progeny of high- and low-feed-conversion sires. Differences between progeny of high- and low-feed conversion sires tended to exist (P < .10) for heart girth (176.3 +/- 1.2 vs 173.2 +/- 1.2 cm) and were significant for backfat thickness (.94 +/- .01 vs .87 +/- .02 cm). No significant differences were observed for hip height (115.3 +/- .5 vs 115.5 +/- .5 cm), chest depth (58.8 +/- .6 vs 57.4 +/- .6 cm), chest width (44.4 +/- .5 vs 44.0 +/- .5 cm), head width (21.2 +/- .2 vs 21.1 +/- .2 cm), head length (42.4 +/- .3 vs 41.6 +/- .3 cm), muzzle circumference (41.0 +/- .4 vs 41.6 +/- .3 cm), length between hooks and pins (46.7 +/- .5 vs 46.2 +/- .5 cm), length between shoulder and hooks (94.9 +/- 1.0 vs 93.1 +/- 1.0 cm), or volume (361,199 +/- 4,885 vs 352,718 +/- 5,026 cm3). PMID- 8440653 TI - Ten-year linear trends in reproduction and wool production among inbred and noninbred lines of Rambouillet, Targhee, and Columbia sheep. AB - To investigate the value of creating inbred lines for genetic improvement of sheep, 54 inbred, 1 randombred control, and 3 noninbred control lines were evaluated for lamb and wool production. Results were based on 19,438 dam and 23,625 lamb records from Rambouillet (R), Targhee (T), and Columbia (C) sheep collected over 9 yr (for T and C) and 10 yr (for R), starting in 1954. Average inbreeding in the inbred lines during the period was near 25% for lambs and 20% for ewes. The general trend in inbred lines for litter weight weaned (120 d) and number weaned (net reproductive rate), per ewe exposed to breeding, was downward as inbreeding increased. Trends in fleece weight generally also were down, regardless of concomitant increases in body weight. Declines were most pronounced in two lines developed by rapid inbreeding. Reproductive merit in the R and C noninbred controls also declined, but the declines were less than those for most inbred lines. Although the T noninbred control declined in fleece weight, trends for fleece weight in the R and C controls were positive and significantly different from the negative trends in the inbred lines. For the randombred control, slight downward trends in litter weight and number weaned were less (P < .05) than those for most inbred lines, indicating genetic declines in these traits for most inbred lines. Direct selection for an index of overall phenotypic merit, recurrent selection for combining ability for overall merit, and direct selection for body type, clean fleece weight, or staple length were all ineffective in preventing a decline in reproductive merit. Ending means (last 2 yr of production) revealed that litter weight weaned in the control groups of each breed was clearly superior to that in most inbred lines. Controls also were typically superior for fleece and body weight. Not one of the 54 inbred lines was superior (P < .05) to its respective noninbred control in weight of lamb weaned or net reproductive rate. Only four of the inbred lines were superior to the noninbred controls in fleece weight. These results, after at least 23 yr of development for most lines, reflect little encouragement for the costly development of many inbred lines for the purpose of improving lamb and wool production, especially when using the above selection criteria. PMID- 8440654 TI - Relationship of maternal milk expected progeny differences to actual milk yield and calf weaning weight. AB - Calf weaning weights and estimates of 205-d milk yield (n = 317) were obtained from 90 Polled Hereford (PH) and 80 Simmental (SM) cows to evaluate the relationship of these measures with maternal milk and total maternal EPD from national cattle evaluations. An inverse parabolic exponential function predicted 205-d milk yields for each cow from five estimates of daily milk yield taken once per month via calf weigh-suckle-weigh. Changes in calves' 205-d adjusted weights were greater than predicted (P < .02) by maternal milk EPD of PH and SM dams and PH maternal grandsires (MGS) but were similar to changes predicted by SM MGS (P > .50). These changes were also greater than those predicted by total maternal EPD of PH dams and MGS (P < .02) but were similar to those predicted in SM dams and MGS (P > .38). Interactions of maternal milk and total maternal EPD with sex of calf and year did not influence calves' 205-d adjusted weights (P > .10). A positive relationship was found in both breeds between 205-d milk yield EPD (calculated from 205-d milk yield estimates) and maternal milk EPD from national cattle evaluations. Objectively assessing the magnitude of this relationship was hindered by problems in estimating heritability and interpreting correlations between EPD. These data indicate that maternal milk and total maternal EPD from national cattle evaluations are reasonably good predictors of genetic differences in milk yield and weaning weight. PMID- 8440655 TI - Evaluation of Australian merino and U.S. sheep breeds for growth and carcass traits. AB - One hundred twenty 4-mo-old wether lambs born to Targhee ewes and sired by six rams each from Merino (Finewool, FM and Strongwool, SM), Rambouillet (Dubois, DR and Texas, TR), and Targhee (T) breeds were randomly assigned to predetermined slaughter weight groups of 43, 48, 52, and 57 kg and evaluated for growth and carcass traits. Overall mean ADG and feed conversion rate (FC, kilograms of feed/kilogram of gain) were .28 and 6.4 kg, respectively; T grew the fastest (.31 kg) and FM grew the slowest (.23 kg). Targhee and SM had the best FC (6.2), whereas FM (6.8) had the poorest FC (P < .05). Overall mean backfat thickness (BT) and carcass fat (CF) were 4.8 mm and 25.6%, respectively. Targhee had the lowest (24%) and FM the highest (27.8%) CF percentage (P < .05). Differences (P < .05) were observed for BT and CF among slaughter weight groups; overall means for both traits gradually increased from the 43- to the 57-kg groups. Separate analysis of the 43- and the 48-kg groups indicated nonsignificant breed differences for feed traits, whereas significant differences still existed for CF. It was concluded that Merino strains grew more slowly, were less efficient in postweaning growth, and had higher carcass fat content than U.S. breeds at a constant slaughter weight; SM were more comparable to U.S. breeds than were FM. Merino-cross lambs should be slaughtered at lighter BW to avoid excessive carcass fat. PMID- 8440656 TI - Technical note: a pressure-sensitive sensor for measuring the characteristics of standing mounts of cattle. AB - A pressure-sensitive sensor that reacts to pressure by changing its electrical resistance was used to measure the characteristics of standing mounts of estrous cattle. While an estrous heifer fitted with a sensor on the rump was standing when mounted by a bull (i.e., during a standing mount), the sensor reacted to the addition and removal of pressure against it by the bull. The times of electric contact signals produced by these pressure changes were recorded to pinpoint the time of the mounted response and the duration of the mount. To detect the characteristics of standing mounts accurately, three types of sensors with different sensitivities and various positions on the rump of heifers were examined. When 13.5-cm sensors that operated with a pressure of 1,000 g/cm2 were fitted on the line combining the highest points of the left and right hip bones toward the tail, or 6.5 cm behind this position, on the rump of heifers (200 to 225 kg), mounts by vasectomized bulls (278 to 556 kg) were accurately recorded with the sensors more than 85% of the time. However, the correlation between the observed and automatically recorded lengths of mounting varied with combinations of the mounted and mounting animals or with locations of the sensor (r = .19 to .86). The pressure-sensitive sensor proved to be a promising device for continuously measuring the characteristics of standing mounts, especially the exact time at which a mount occurs. PMID- 8440657 TI - Experience with blackbrush affects ingestion of shrub live oak by goats. AB - Generalization occurs when an animal responds to novel stimuli in much the same way it has responded to similar, familiar stimuli. Our objective was to determine whether goats generalized foraging skills from older growth blackbrush (Coleogyne ramosissima) to shrub live oak (Quercus turbinella). Blackbrush (OGBB) has small leaves that are difficult to ingest without the twigs, whereas shrub live oak (SLO) has larger leaves that can be ingested easily without twigs. In Yr 1, 6-mo old goats and in Yr 2 18-mo-old goats were given experience browsing with OGBB for 0, 10, 20, or 30 d. They were next tested for 5 min/d for 2 d on OGBB, and then tested in the same way on SLO. The number of bites and bite rate increased significantly as goats of both ages gained experience browsing OGBB. Likewise, goats with more experience browsing OGBB took more bites during a 5-min period when foraging on SLO. Thus, goats generalized foraging skills from OGBB to SLO. Plant life form also affected the response of goats. Total intake, intake rate, and bite size were significantly higher for SLO than for OGBB. There was an interaction between level of experience and plant life form. The interaction occurred because goats with no experience browsing OGBB took more bites per 5 min of SLO than of OGBB, whereas goats with increasing levels of experience browsing OGBB generally took more bites of OGBB than of SLO. Controls took more bites per 5 min of SLO than of OGBB, because SLO leaves could be ingested (harvested and chewed) more easily than OGBB twigs. PMID- 8440658 TI - Comparison of the growth-promoting properties of daily versus continuous administration of somatotropin in female rats with intact pituitaries. AB - The effect of dose and mode of delivery of recombinant bovine (rbST) or porcine somatotropin (rpST) on the growth rate of female rats with intact pituitaries was investigated in a series of experiments. The overall objective of these studies was to compare the relationship of dose and mode of delivery on the growth response to somatotropin. The equivalence of rbST and rpST in stimulation of growth was demonstrated. In an initial study, treatment of rats with 0, .67 (3 mg/kg), or 2.0 mg/d (9 mg/kg) of rbST for 28 d resulted in ADG of .8, 2.6, and 3.8 g/d (P < .0001, SEM .1 g). A log-linear dose response to rbST in the range of .07 to 32 mg/d (.3 to 145 mg/kg) for the stimulation of gain was observed. Continuous delivery of rpST in bicarbonate buffer was achieved using osmotic pumps. Sustained, log-linear growth for doses of 0, .5, 1, 2, and 4 mg of rpST/d for 28 d was demonstrated. In a direct comparison of bolus injection and continuous delivery at doses of 0, .22, .67, 2.0, and 6.0 mg of rpST/d, a significant difference in slope (P < .0001) of the modes of delivery was observed; continuous delivery had a greater slope. Depending on the dose administered, bolus injection was either more (< .67 mg/d) or less efficacious (> .67 mg/d) than continuous delivery in its ability to stimulate growth in female rats with intact pituitaries. It is hypothesized that the difference in the slope of the dose-response curves can be accounted for by the animal's ability to utilize the hormone effectively. PMID- 8440659 TI - Determination of the relative abundance of skeletal muscle alpha actin mRNA in muscle of livestock species. AB - Three market-weight animals of meat-producing livestock species were slaughtered to obtain porcine (barrows), bovine (steers), ovine (wethers), and avian (cockerels) tissue samples. The four tissues of interest were skeletal muscle, heart, smooth muscle (stomach or gizzard), and liver. Total RNA was isolated from each tissue and then hybridized to a human skeletal (sk)-alpha-actin [32P]cDNA probe using both dot blot and Northern blot hybridization. No hybridization was observed with RNA from liver or smooth muscle from any of the species, suggesting little or no hybridization to nonmuscle and smooth muscle beta- and gamma-actin isoforms. The human sk-alpha-actin probe hybridized to RNA from skeletal muscle of pigs, cattle, sheep, and chickens, although relative hybridization was 75% less with chicken RNA. The hybridization was limited specifically to a band at 1.6 kb (kilobases), the known length of sk-alpha-actin mRNA. Hybridization was observed with RNA from pig heart (1.6 kb) and the relative abundance was consistently 7 to 10% of that observed with porcine skeletal muscle, even as stringency conditions were increased. These results indicate that the human sk alpha-actin probe can be used to determine alpha-actin mRNA expression in skeletal muscle for pigs, cattle, and sheep. PMID- 8440660 TI - The effect of live weight gain and live weight loss on body composition of merino wethers: noncarcass organs. AB - The weight of the noncarcass external tissues, thoracic organs, and visceral organs was measured during live weight gain (LWG) and live weight loss (LWL) to evaluate the effect of different periods of normal and retarded growth on noncarcass organs. Thirty-five Merino wethers were allowed ad libitum access to an experimental diet of 80% alfalfa chaff and 20% cereal grain (17.23% CP and 12.09 MJ/kg of DE) to grow from 23.0 to 33.0 kg live weight and then fed to lose 10 kg at 133 g/d. Groups of five animals were slaughtered at live weights of 23.0, 26.3, 29.6, and 33.0 kg during LWG and 29.6, 26.3, and 23.0 kg during LWL. Although total weight of noncarcass organs was significantly lower in LWL animals than in LWG animals at 23.0- and 26.3-kg (P < .05) common slaughter weights, the weight of some noncarcass organs was significantly greater in LWL animals. For example, the weight of the head at 23.0 and 26.3 kg (P < .05), of the feet and esophagus at 23.0 (P < .01) and 26.3 kg (P < .05), and of the total alimentary tract fat at 23.0 kg (P < .01) was greater in LWL wethers. Weights of other organs, however, were lower in LWL animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8440661 TI - Measurement of zeranol in plasma from three blood vessels in steers implanted with zeranol. AB - Zeranol (Z) is a widely used growth promotant; however, plasma Z profiles in cattle implanted with Z have not been characterized. This study was conducted to determine bovine plasma Z profiles. In Exp. 1, four steers (BW = 284.8 +/- 5.6 kg) were implanted with 108 mg of Z (Ralgro). To determine the effect of sampling site on plasma Z concentrations, blood was sampled by venipuncture from the maxillary vein ipsilateral (IMV) to the ear in which Z was implanted and from the ipsilateral (IJV) and contralateral (CJV) jugular veins of each steer. Samples were collected on d 1, 4, 6, 8, 11, and 13 after implantation and Z was assayed by RIA. There was an effect of sampling site (P < .01). The overall mean plasma Z concentrations and 95% confidence intervals (CI) for each vessel were 282 (CI: 172 to 463), 135 (CI: 85 to 215), and 67 (CI: 42 to 106) pg/mL for the IMV, IJV, and CJV, respectively. Plasma Z concentration was higher (P < .05) in IMV than in IJV and higher (P < .05) in IJV than in CJV. In Exp. 2, nine steers (BW = 316.7 +/- 10.0 kg) were implanted with 108 mg of Z and IMV blood was collected on d 0, 1, 3, 7, 10, 14, 17, 21, 28, 35, 42, 56, 63, 73, and 91 after implantation. Day affected plasma Z concentration (P < .01); plasma Z was elevated above preimplantation levels for 91 d (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8440662 TI - Effect of the genotype for malignant hyperthermia as determined by a restriction endonuclease assay on the quality characteristics of commercial pork loins. AB - A total of 913 boned pork loins were selected in a commercial cutting operation on the basis of color measured by a Colormet surface colorimeter. Color (L, a, b values) at three locations, free water, and ultimate pH were measured on each loin. In addition, the genotype with respect to malignant hyperthermia was determined by a restriction endonuclease assay. Six hundred ninety-three loins were determined to be of normal (NN) genotype, 198 heterozygote (Nn), and 22 homozygote (nn). This distribution reflected the selection strategy and not the incidence in the general population. Meat was darker (P < .01) and free water was reduced (P < .01) in NN loins compared to Nn or nn loins. Ultimate pH was lower (P < .01) in Nn loins than in NN loins. An increase in the incidence of Nn or nn meat samples was observed as the paleness of the loins or their free water content increased, or as the ultimate pH of the meat decreased. Based on this study, approximately 30% of meat classified as PSE on a color basis would come from heterozygote pigs. PMID- 8440663 TI - Body composition of postpubertal gilts at nutritionally induced anestrus. AB - An experiment using comparative slaughter was conducted to examine the relationship between occurrence of nutritionally induced anestrus in postpubertal gilts and chemically determined body composition and body composition changes. Thirty-nine Duroc x (Yorkshire x Landrace) gilts, each having experienced three or more estrous cycles, were used. Nine gilts were chosen randomly, weighed, ultrasonically scanned for 10th rib backfat thickness, and slaughtered to determine initial body composition. Remaining gilts were allotted randomly to five dietary treatments, four characterized as severely energy restrictive (RES; .25, .50, .75, and 1.0 mcal of ME/d) and a control (3.4 Mcal of ME/d). Dietary treatments provided equal amounts of protein (50 g), minerals, and vitamins daily. Individual serum progesterone levels were determined every 3 d using RIA and gilts were considered anestrous when concentrations were < 1.0 ng/mL for four consecutive samples (9 d). All RES gilts became anestrous, and gilts restricted more severely tended (P = .22) to do so more quickly. Days to anestrus were 66.0 +/- 12.0, 77.4 +/- 13.1, 84.5 +/- 12.0, and 86.5 +/- 12.0 for treatments .25, .50, .75, and 1.0, respectively. Among RES treatments there were no linear, quadratic, or cubic effects of ME intake (P > .10) on the quantity of body protein or fat lost, or on the quantity of body protein or fat remaining at anestrus. However, individual body protein and body fat contents of RES gilts at slaughter revealed that anestrus occurred at a wide range of body compositions, from 13.4 to 20.2 kg of protein and .36 to 27.0 kg of fat. This wide range of individual values suggests that estrous activity in the mature gilt is not controlled by specific threshold levels of body reserves. PMID- 8440664 TI - Estrous cycle characteristics of postpubertal gilts approaching anestrus due to limited dietary energy intake. AB - Twenty-nine Duroc x (Yorkshire x Landrace) gilts, approximately 9 mo of age and each having experienced at least three estrous cycles, were allotted randomly to five dietary treatments. Each treatment provided a different daily intake of metabolizable energy: .25, .5, .75, 1.0 Mcal (severely restrictive [RES]; chosen to cause cessation of estrous cycles) or 3.4 Mcal (control; designed for maintenance of estrous cyclicity). Blood samples were drawn by venipuncture every 3 d and sera were assayed for progesterone (P4) concentration. Estrous cycle length was estimated by defining d 0 as the last day when serum P4 concentrations were < 1 ng/mL before increasing to > 1 ng/mL. Gilts were considered acyclic when serum P4 levels remained < 1 ng/mL for four consecutive samples (9 d). Anestrus occurred after 78.7 +/- 6.1 d in all RES gilts (n = 23) and in one control on d 24. Compared with the control treatment, RES treatments resulted in longer (P < .05) average estrous cycles (21.0 +/- .2 vs 20.2 +/- .3 d) and greater (P < .05) mean serum P4 concentrations (13.7 +/- .4 vs 11.4 +/- .8 ng/mL). There were no differences in P4 or cycle length measurements among RES treatments. Cycle duration and serum P4 concentrations of the final estrous cycle before anestrus were similar to those of previous cycles. It is concluded that severe energy restriction caused elevated serum P4 concentrations. Neither cycle length nor serum P4 concentration was notably altered as gilts neared anestrus. PMID- 8440665 TI - Amino acid supplementation of low-protein sorghum-soybean meal diets for 20- to 50-kilogram swine. AB - Five growth experiments (28 or 35 d in duration) with growing pigs (24 kg initially) were conducted to assess the value of added threonine, tryptophan, methionine, and isoleucine in low-protein, lysine-fortified, sorghum-soybean meal diets. Basal 12, 13, and 14% CP diets were fortified with lysine.HCl to contain .62% digestible lysine, the lysine content of the 16% CP control diet included in all experiments. The additions of .12% threonine (.54 vs .42% dietary threonine) to the 12% CP diet in Exp. 1 improved (P < .01) ADG and gain/feed, but additions of .05% tryptophan or .10% methionine were without effect. Interactions of threonine, methionine, and tryptophan additions were nonsignificant (P > .30). Increasing lysine from .71 to .86% or increasing threonine from .54 to .65% in 12% CP diets of Exp. 2 improved (P < .07) gain/feed but did not affect ADG. Neither the addition of .05% isoleucine nor the addition .46% NaHCO3 to the 12% CP diet in Exp. 3 affected performance. All 12% CP diets in Exp. 1 to 3 resulted in performance below that obtained on the 16% CP diet. Addition of threonine to 13% CP (.47 vs .55% threonine, Exp. 4) or 14% CP (.51 vs .58% threonine, Exp. 5) diets tended (P < .12) to improve gain/feed but did not affect ADG. Performance on the 14% CP diet with added threonine and on the 16% CP diet was equivalent. These data suggest a minimum of 14% CP is needed in lysine-threonine fortified, sorghum-soybean meal diets of growing pigs for maximum performance. PMID- 8440666 TI - Amino acid supplementation of low-protein sorghum-soybean meal diets for 5- to 20 kilogram swine. AB - Four growth experiments were conducted to determine the value of added threonine (Thr), methionine (Met), tryptophan (Trp), and isoleucine (Ile) in low-protein, lysine (Lys)-fortified, sorghum-soybean meal diets for starting pigs weaned at 28 d. Trials lasted 28 d and average initial weight was approximately 6.5 kg. A 21% CP (1.15% total and .95% digestible Lys) diet was included in all trials. Basal 15, 17, and 19% CP diets were formulated to contain .95% digestible Lys by adding .38, .26, and .13% Lys, respectively. In Exp. 1, the additions of either Thr (.27%) or Met (.08%) to the 15% CP diet improved (P < .05) ADG and gain/feed (G/F); Trp (.04%) and Ile (.05%) additions had no effect. None of the 15% CP diets resulted in performance comparable to that obtained on the 21% CP diet. In Exp. 2, 19 and 17% CP diets fortified with Thr, Met, and Trp to obtain the digestible contents of the 21% CP diet produced performance equal to performance on the 21% CP diet. Results of Exp. 3 indicate that Thr (.11%) and Met (.08%) supplementation of the 17% CP diet were needed to maximize performance; Trp and Ile additions were not beneficial. Results of the final experiment suggested that Thr and Met additions to the 17% CP diet could be reduced to .05 and .04%, respectively, without lowering performance. These data indicate that a 17% CP, sorghum-soybean meal diet fortified with Lys, Met, and Thr can produce performance equal to that obtained by pigs fed a 21% CP diet. PMID- 8440667 TI - Effects of fumonisin-contaminated corn screenings on growth and health of feeder calves. AB - Fumonisins are myocotoxins produced by Fusarium moniliforme and F. proliferatum, common molds of corn in North America. The toxin is at especially high concentrations in corn screenings. Fumonisins are toxic to swine and horses, but effects of these toxins in cattle have not been evaluated. This experiment was conducted to determine the effects in cattle of feeding fumonisins at levels known to be toxic to swine and horses. A total of 18 crossbred feeder calves were fed diets containing fumonisins at 15, 31, or 148 micrograms/g for 31 d. Feed consumption, weight gain, complete blood count, serum clinical chemistries, and an immune function profile were done on d -3, 4, 10, 17 and 31 relative to the start of fumonisin feeding. There was no treatment-related effect on feed intake or weight gain, but feed containing 148 micrograms/g of fumonisins seemed to be less palatable than other feeds. Significant increases in serum aspartate amino transferase, gamma glutamyl transpeptidase, lactate dehydrogenase, bilirubin, and cholesterol occurred from d 10 through 31. Mild microscopic liver lesions were present in two calves fed at the highest fumonisin level. Lymphocyte blastogenesis was significantly impaired at the end of the feeding period in the group given the highest dose. Other measures of immune function were not affected significantly. Fumonisins are capable of causing changes in liver function and in some measures of immune function. However, cattle seem to be relatively less susceptible to fumonisins present naturally in grains than either swine or horses. PMID- 8440668 TI - Technical note: an improved method for extraction and quantification of toxic phenethylamines from Acacia berlandieri. AB - N-methyl-beta-phenethylamine (NMPEA) has been previously identified as the toxin causing locomotor ataxia in sheep and goats grazing the browse plant, Acacia berlandieri. We describe a simplified procedure for extraction and quantification of naturally occurring beta-phenethylamines from this Acacia species. Dried, ground plant tissue was extracted (1:20 wt/vol) with 1% glacial acetic acid and filtered. The filtrate was passed through a high-sulfonated polymeric solid-phase extraction (SPE) tube, which retained the compounds of interest (tyramine, hordenine, NMPEA) but allowed many impurities co-extracted from the plant tissue to be washed through. Amines were eluted from the tube, then separated and detected by reversed-phase HPLC. Extracted amines were resolved by HPLC in < 15 min, and UV-absorbance spectra matched those of authentic standards. Recovery efficiency of amine standards (125 micrograms/mL) from SPE tubes averaged 97, 101, and 98% for tyramine, hordenine, and NMPEA, respectively. Excess sample loss was prevented and the large volumes of solvents required for liquid-liquid extraction eliminated by use of solid-phase extraction techniques. PMID- 8440669 TI - Innate variability in sexual development irrespective of body fatness in gilts. AB - To separate the effects of fatness from those of lean tissue growth on reproductive development, 52 gilts (33.2 kg, 75 d) had ad libitum access to a high-energy diet (HE; n = 31) or were fed restrictively a low-energy diet (approximately 80% of ad libitum; LE; n = 31) until 160 d of age. All HE and 15 LE gilts were then slaughtered; the 16 LE gilts that remained were then allowed ad libitum access to the low-energy diet until slaughter at 175 d (LER). Twelve littermate trios allocated across treatments were cannulated and bled during both unfed and fed states before slaughter. Gilts in the HE group were 8 kg heavier, 3.5 mm fatter (backfat), and consumed 14.9 MJ of DE more per day than gilts in the LE group at 160 d (hereafter P < .05); LER gilts were 7 kg heavier, 2.2 mm fatter, and consumed 21 MJ of DE more per day at 175 d than LE gilts at 160 d. Carcass fat was lower in LE gilts than in HE or LER gilts, but carcass lean was similar among groups. Treatment did not affect basal or episodic LH or growth hormone secretion, reproductive tract weight, follicular volume, or plasma or follicular fluid estradiol-17 beta. Postprandial plasma insulin was greater in LER than in HE or LE gilts, but plasma insulin-like growth factor I and urea nitrogen were similar among groups. Plasma nonesterified fatty acids and creatinine were greater in HE than in LE or LER gilts. These results suggest that when protein accretion rate is maximal, differences in fatness do not influence reproductive development in the prepubertal gilt. Irrespective of treatment, the only measured factor showing an association with ovarian development was the innate variability in episodic and basal LH secretion. PMID- 8440670 TI - Responsiveness of porcine large and small luteal cells to luteotropic or luteolytic hormones and cell morphologic changes during the estrous cycle and pregnancy. AB - Isolated porcine luteal cells from d 10 and 15 of the estrous cycle (estrus = d 0) were incubated with or without combinations of FSH (0, 10, 10(2), 10(3) ng), LH (0, 10, 10(3) ng), oxytocin, or prostaglandin F2 alpha (PGF2 alpha) (each at 0, 10, 10(3), and 10(5) pg). Progesterone (P4) content was determined after overnight incubation (0 h) then at 2 and 24 h of incubation. The basal (0 h) P4 production of large cells (LC) from d 10 corpora lutea (CL) was 31-fold higher than that by small cells (SC) at 0 h. The LC and SC from d 10 but not those from d 15, were stimulated to a small extent by LH (P < .05). The FSH inhibited P4 production (P < .05) by SC at 24 h on d 10 and by LC after 2 or 24 h of incubation on d 15. There was no interaction between LH and FSH on P4 production. Oxytocin and PGF2 alpha decreased P4 production by d 15 LC at 2 h of incubation (P < .05) and by d 15 SC after 2 or 24 h of incubation (P < .05 and P < .01). The morphology of cells from CL of the cycle or early or mid pregnancy were examined using scanning and transmission electron microscopy (EM). Freshly isolated LC (using scanning EM) from d 10 contained many microvilli arranged in apparent networks on their membranes, but SC had smooth surfaces and contained only a few microvilli. Internally, LC had more small mitochondria than did SC and a different organization of smooth endoplasmic reticulum (SER). The SC from CL of pregnant (d 30 to 60) gilts contained more mitochondria than SC from CL of cyclic gilts. The results indicate that FSH, oxytocin, and PGF2 alpha can have a direct cellular luteolytic effect in the late luteal phase in pigs. The FSH influenced LC, whereas oxytocin and PGF2 alpha effected a more pronounced decrease in P4 from SC. The lower amount of P4 produced overall by SC may be associated with fewer microvilli, mitochondria, and SER in SC. PMID- 8440671 TI - Wool production and blood supply to skin and other tissues in sheep. AB - Quantitative measurements of blood flow (BF) to skin and several other tissues were made using radioactive microspheres in conscious sheep. The sheep were from established flocks that had been selectively bred for greater (Fleece plus) or lesser (Fleece minus) wool production. The BF rate per unit area of wool-bearing skin was significantly greater in the Fleece plus (n = 9) than in the Fleece minus (n = 6) group, but the correlation between skin BF and the wool growth rate in individual animals was modest (r = .581). There was a strong, positive correlation (r = .813) between wool production and pineal BF. Other tissues that exhibited significant BF differences between the two groups included adrenal glands and fat, which were greater in Fleece plus sheep, and thyroid glands, reticulum, rumen, and extremity skin (non-wool-bearing), which were lesser in Fleece plus sheep.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8440672 TI - Effect of methionine addition to a urea-grain supplement on intake and digestibility of mature, dormant grasses and performance of cows grazing winter range. AB - A digestibility trial involving 20 Hampshire ram lambs and a 2-yr grazing study using 103 mature crossbred cows were conducted to determine the effects of methionine addition to a urea-grain supplement on intake and digestibility of dormant range grasses and on cow performance. In each trial, four treatment groups were supplemented with either a urea-grain control (CON), urea-grain plus methionine (MET, 3.3% DL-methionine), urea-grain plus inorganic sulfur (SUL, 3.0% sodium sulfate), or soybean meal (SBM). Supplements were designed to provide 45 and 360 g of CP.animal-1.d-1 (lambs and cows, respectively) and were balanced for ME, Ca, P, and K. Lambs had ad libitum access to mature prairie hay, whereas cows grazed dormant winter range from mid-November until mid-February. For the grazing study, forage OM intake (OMI) was determined in late November and in late January by the fecal output/indigestibility ratio technique. Controlled-release chromic oxide boluses were used as an external marker to estimate fecal output, and acid insoluble ash was used as an internal marker to predict OM digestibility (OMD). Mean daily DMI of mature prairie hay was 1,057 g/lamb and was not affected by supplementation. Apparent DM, NDF, and ADF digestibilities and N biological value did not differ (P > .10) among treatments. Nitrogen digestibility was increased (P = .06) for lambs fed the MET or SUL compared with CON.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8440673 TI - Predictions of the nutrient composition of the diets of supplemented versus unsupplemented grazing beef cows based on near-infrared reflectance spectroscopy of feces. AB - Near-infrared reflectance spectroscopy of fecal samples from crossbred beef cows grazing native range forage was performed to determine whether supplemental feeding would alter the prediction of forage quality. In one trial, 2.27 kg.cow-1 x d-1 of supplemental feed with 20% CP and 3.3 Mcal of DE/kg had a detectable, but unimportant, effect on the predicted forage digestibility of OM, whereas the predicted forage content of CP was increased from 5.6 to 6.4% (P < .01). In a second trial at another location, supplemental feeding of isonitrogenous (700 g.cow-1 x feeding-1) feeds that provided low, medium, or high levels of DE three times weekly caused detectable, but unimportant, changes in the predicted digestibility of forage OM, whereas important changes were noted in the predicted CP content of grazed forages. Although forage quality could not be evaluated from spectra developed with unsupplemented cows, a change in the plane of nutrition was detectable. In the first trial, apparent effects of supplemental feeding on predicted diet quality were not detected if fecal sampling occurred 36 or 56 h after the supplemental feeding ceased for CP and OM digestibility, respectively. Whether supplemental feeding altered the grazing behavior of cows and quality of forage grazed, or merely altered composition of fecal samples, was not determined. PMID- 8440674 TI - Double-stranded RNA virus replication and packaging. PMID- 8440675 TI - Regulation of alpha 2,3-sialyltransferase expression correlates with conversion of peanut agglutinin (PNA)+ to PNA- phenotype in developing thymocytes. AB - Staining of thymus tissue with the plant lectin peanut agglutinin (PNA) is a classic technique for defining the cortical (PNA+) and medullary (PNA-) regions of this tissue. These two regions are primarily composed of immature and mature thymocytes, respectively. Conversion of the PNA+ to the PNA- phenotype has been attributed to masking of the cell surface carbohydrate receptors of PNA by sialic acid during the intrathymic maturation of these cells. We present evidence that the regulated expression of a single glycosyltransferase, a Gal beta 1,3GalNAc alpha 2,3-sialyltransferase, can account for this glycosylation change. This enzyme sialylates the preferred ligand of PNA, Gal beta 1,3GalNAc, forming the sequence NeuAc alpha 2,3Gal beta 1,3GalNAc, thus masking PNA binding sites. Expression of the enzyme is inversely proportional to expression of the PNA receptor, as evidenced by analysis of T-lymphoblastoid cell lines and by in situ hybridization experiments in human thymic tissue. PMID- 8440676 TI - Inhibition of glucose trimming by castanospermine results in rapid degradation of unassembled major histocompatibility complex class I molecules. AB - The CMT-cKd1 cell line provides a system for studying the initial processing steps of N-linked oligosaccharides as these cells have been shown to produce major histocompatibility complex (MHC) class I molecules which, due to a defect in assembly, recycle between the endoplasmic reticulum and a pre-Golgi compartment, failing to reach the cell surface (Hsu, V.W., Yuan, L. C., Nuchtern, J. G., Lippincott-Schwartz, J., Hammerling, G. J., and Klausner, R. D. (1991) Nature 352, 441-444). In the present study we observed that when the MHC class I heavy chain of these CMT cells was pulse-radiolabeled with [35S]methionine in the presence of the glucosidase inhibitor, castanospermine (CST), it underwent a rapid degradation during a 60-min chase, in contrast to control cells in which it remained stable during that period. The CST-promoted instability of the MHC molecule appeared to be specific, as it did not occur when 1-deoxymannojirimycin, an inhibitor of mannosidase, was added to the cells. Although endomannosidase was found to be present in the CMT cells, the electrophoretic mobility of the MHC heavy chain produced in the presence of CST indicated that deglucosylation through the alternate route provided by this enzyme did not occur. Furthermore, gamma-interferon did not prevent the rapid disappearance of the MHC molecule, although it brought about entry of this glycoprotein into the secretory pathway in cells incubated without CST. The results of our studies suggest that retention of glucose on N-linked oligosaccharides may under certain circumstances provide a signal for pre-Golgi protein degradation. PMID- 8440677 TI - Germ cell beta-chimaerin, a new GTPase-activating protein for p21rac, is specifically expressed during the acrosomal assembly stage in rat testis. AB - Diverse GTPase-activating proteins (GAPs) for the p21rho subfamily were detected by a novel overlay assay (Manser, E., Leung, T., Monfries, C., Teo, M., Hall, C., and Lim, L. (1992) J. Biol. Chem. 267, 16025-16028), with some GAPs being tissue specific. Using a PCR strategy exploiting conserved regions common to rho/rac GAPs, we have isolated a rat testis cDNA encoding a 34-kDa rac-GAP termed beta chimaerin, as it was highly related to n-chimaerin, containing both a GAP domain (77% identity) and the phorbol ester-binding region (93% identity). beta Chimaerin mRNA is expressed exclusively in the testis at the onset of sexual maturation. In situ hybridization and cell fractionation analyses show beta chimaerin mRNA expression to be stage-specific, paralleling acrosomal assembly at the late stage of spermatogenesis. A corresponding testis-specific 30-kDa rac-GAP was detected. The testis-specific and stage-dependent expression of this new member of the chimaerin family offer an alternative model system for investigating the functional role of this class of p21 GAPs, particularly in relation to cytoskeletal reorganization. PMID- 8440678 TI - Stimulation of specific types of Gs-stimulated adenylyl cyclases by phorbol ester treatment. AB - Regulation of adenylyl cyclases by protein kinase C was studied. Types 1-6 were transiently expressed in 293 cells. The cells were treated with 4 beta-phorbol 12 myristate 13-acetate (PMA), and adenylyl cyclase activity was measured. PMA treatment of untransfected or vector-transfected cells resulted in a 35% (mean) increase in basal and forskolin-stimulated activity. PMA treatment of type 2 enzyme-transfected cells showed a 3-fold increase in basal activity. This stimulation varied with Mg2+ concentration with up to 4.5-fold increases at low Mg2+. PMA treatment resulted in about a 60% increase in fluoride or GTP gamma S (guanosine 5'-O-(thiotriphosphate))-stimulated activity in type 2 enzyme transfected cells. Expression of the type 1 and 3 enzymes resulted in pronounced Ca2+/calmodulin stimulation, which was significantly increased upon pretreatment with PMA. No effects of PMA treatment were observable on other activities of the type 1 enzyme, whereas all activities of the type 3 enzymes were stimulated. Expressed types 4, 5, and 6 enzymes showed modest (approximately 30%) or no increases in basal and forskolin-stimulated activities upon PMA treatment. These data indicate that specific types of adenylyl cyclases can be functional targets for protein kinase C. The pronounced effects on the basal activity of the type 2 enzyme suggest this adenylyl cyclase could in the appropriate environment be an intracellular signal generator for external signals not routed through the activation of Gs. PMID- 8440679 TI - Identification and characterization of a binding site for factor XIIa in the Apple 4 domain of coagulation factor XI. AB - Previously we have characterized a binding site for high M(r) kininogen in the first of four tandem-repeat (Apple) domains within the heavy chain region of factor XI (Baglia, F. A., Jameson, B. A., and Walsh, P. N. (1990) J. Biol. Chem. 265, 4149-4154; Baglia, F. A., Jameson, B. A., and Walsh, P. N. (1991) J. Biol. Chem. 267, 4247-4252), whereas a substrate binding site for factor IX was localized to the second Apple (A2) domain (Baglia, F. A., Jameson, B. A., and Walsh, P. N. (1991) J. Biol. Chem. 266, 24190-24197). To define the factor XI domain that binds factor XIIa, we have screened a panel of synthetic peptides for their capacity to inhibit factor XI activation by factor XIIa. Peptide Gly326 Lys357 (located in the A4 domain) is a noncompetitive inhibitor of factor XI activation by factor XIIa (Ki = 3.75 microM), whereas structurally similar peptides from the A1, A2, and A3 domains were required at > 1000-fold higher concentrations for similar effects. The same peptide (Gly326-Lys357) is a competitive inhibitor of factor XIIa amidolytic activity (Ki = 3.8 microM) suggesting that it binds near the active site of factor XIIa. Computer modeling was used to predict the secondary and tertiary structure of the A4 domain of factor XI that interacts with factor XIIa. Rationally designed, conformationally constrained peptides were synthesized comprising residues Ala317-Gly326, Lys331 Lys340, and Gly344-Gly350, which act in concert to inhibit factor XI-activation by factor XIIa. Finally, a conformationally constrained peptide spanning residues Ala317-Gly350 inhibits factor XIIa-catalyzed factor XI activation 50% at a concentration of 5 x 10(-7) M. These results, interpreted in the context of the model, suggest that the sequence of amino acids from Ala317 through Gly350 of the heavy chain of the A4 domain of factor XI contains three peptide structures, possibly consisting of three antiparallel beta-strands that together comprise a contact surface for interacting with factor XIIa. PMID- 8440680 TI - Reduction of mutant phage T4 glutaredoxins by Escherichia coli thioredoxin reductase. AB - Fifteen mutant T4 glutaredoxins (previously T4 thioredoxin) have been assayed for activity with Escherichia coli thioredoxin reductase. The mutations include substitutions in the region of the active site, in the 2 cysteines, and in the 2 residues between the cysteines forming the active-site disulfide bridge. Mutant thioredoxins where substitutions have been made in charged residues around the active site show the biggest differences in activity. The positive residues Lys 13 and Lys-21 were found to be important for efficient binding to thioredoxin reductase. Substitution of the aspartic acid at position 80 with a serine produced a glutaredoxin with superior activity. This mutant glutaredoxin has earlier been shown to be more efficient than the wild type in thiol transferase activity (Nikkola, M., Gleason, F. K., Saarinen, M., Joelson, T., Bjornberg, O., and Eklund, H. (1991) J. Biol. Chem. 266, 16105-16112). Even the glutaredoxin P66A, where the active-site cis-proline has been substituted, could be efficiently reduced by thioredoxin reductase. Glutaredoxins lacking one or both cysteines were not active. PMID- 8440681 TI - The platelet-activating factor acetylhydrolase from human erythrocytes. Purification and properties. AB - Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3- phosphocholine) is a biologically active phospholipid. Tissues, blood cells, and plasma contain PAF acetylhydrolases (calcium independent phospholipase A2 activities) that catalyze the hydrolysis of phospholipids containing short chain sn-2 acyl groups. They inactivate PAF and thereby determine PAF accumulation. We purified the PAF acetylhydrolase from human erythrocytes 15,600-fold. The enzyme has a molecular weight of 25,000, it behaves as a dimer during gel filtration, and it is a previously uncharacterized cytosolic esterase, as it has a unique amino-terminal sequence. The erythrocyte PAF acetylhydrolase requires the addition of sulfhydryl agents for maximal activity, is inhibited by 5,5'-dithiobis(2-nitrobenzoic acid), NaF, diisopropyl fluorophosphate, diethylpyrocarbonate, p-bromophenacylbromide, and a number of proteases. Antibodies against the purified protein precipitate all PAF hydrolase activity from erythrocyte lysates. The erythrocyte PAF acetylhydrolase is specific for short or oxidized sn-2 acyl residues. It exhibits surface dilution kinetics, suggesting that hydrolysis occurs at lipid interfaces. This suggests that this enzyme acts in vivo as a scavenger of oxidatively fragmented phospholipids that are toxic to the cell. PMID- 8440682 TI - Molecular characterization and regulation of the human endothelin receptors. AB - Endothelin receptors (ETRs) are distributed throughout a variety of tissues. Two human cDNAs were identified which encode distinct ETR proteins. One cDNA encoded a 427-amino acid protein that shared 91% identity to rat ETAR. The second cDNA encoded a 442-amino acid protein that was 88% identical to rat ETBR. Ligand binding studies of the cloned receptors expressed in COS cells confirmed that they were pharmacologically ETAR and ETBR subtypes; although the selective antagonist BQ123 showed a potency similar to ET-3 in displacing 125I-ET-1 binding to ETAR. This observation contrasts with rat ETAR pharmacology where BQ123 has a 100-fold higher affinity than ET3. Chinese hamster ovary cells expressing the human ETAR displayed equal potencies in displacing 125I-ET-1 binding, which indicates that rat and human ETAR are pharmacologically distinct. Electrophysiological studies of both ETRs expressed in Xenopus oocytes revealed that they are functional. Northern analysis indicated that the two ETRs are differentially expressed in many tissues. Marmosets maintained on a high fat/high cholesterol diet exhibited 3-fold increase in ETBR mRNA levels with little change in ETAR mRNA levels. Availability of cDNA clones for ETR subtypes can open avenues for future analysis of their role in pathophysiology of various diseases. PMID- 8440683 TI - Characterization of the DNA-melting function of the Rickettsia prowazekii RNA polymerase. AB - In vitro specific transcription by the Rickettsia prowazekii RNA polymerase was investigated. The purified rickettsial RNA polymerase, in striking contrast to that of Escherichia coli, could specifically transcribe two R. prowazekii genes (ATP/ADP translocase and citrate synthase genes) and one E. coli gene (RNA-I) on negative supercoiled plasmids but not the same genes on linear plasmids. Following the specific binding of the rickettsial RNA polymerase to the translocase gene promoter on a linear plasmid, there was no detectable open complex formation. Both the E. coli and the R. prowazekii RNA polymerases worked well when poly(dA-dT).poly(dA-dT) or poly(dI-dC).poly-(dI-dC) was used as template for generalized transcription. However, the rickettsial RNA polymerase, in contrast to the E. coli enzyme, had little activity on poly(dG-dC).poly(dG dC), a template with a larger number of hydrogen bonds. These data indicate that the rickettsial RNA polymerase is weak, at least relative to E. coli, in the function required for the opening of DNA duplex. It appears that this operation in R. prowazekii is aided by the negative supercoiling and the high 72% AT composition of the rickettsial genome. PMID- 8440684 TI - Molecular cloning, DNA sequencing, and biochemical analyses of Escherichia coli glyoxylate carboligase. An enzyme of the acetohydroxy acid synthase-pyruvate oxidase family. AB - Glyoxylate carboligase (Gcl) (EC 4.1.1.47) of Escherichia coli catalyzes the condensation of two molecules of glyoxylate to give tartronic semialdehyde, a key intermediate in glyoxylate catabolism. We report the cloning, genomic location, and DNA sequence of the gene (called gcl) encoding E. coli Gcl and isolation of mutants lacking the enzyme. Gcl is a protein of 593 amino acid residues (64,738 Da) that has a high level (30%) of sequence similarity to the acetohydroxy acid synthases (AHAS) of branched chain amino acid synthetic pathway. Significant sequence identity (26%) was also observed with E. coli pyruvate oxidase, a redox flavoprotein, previously shown to be related to the AHAS enzymes (Chang, Y.-Y., and Cronan, J. E., Jr. (1988) J. Bacteriol. 170, 3937-3945). Consistent with a grouping of Gcl with the AHAS and pyruvate oxidase enzymes. Gcl contains a quinone binding site as well as binding site for thiamine pyrophosphate and FAD. We also found that a gene (orf258) immediately downstream of the gcl gene encoded a protein (Orf258) of 258 residues. Although the gene organization of gcl and orf258 is analogous to that of the ilv gene operons which encode the E. coli AHAS isozyme large and small subunits, Orf258 does not function as a Gcl subunit. Moreover, disruption of the chromosomal copy of orf258 did not affect growth on glyoxylate or glycolate. PMID- 8440685 TI - Interaction of heparin cofactor II with biglycan and decorin. AB - Two small interstitial dermatan sulfate-containing proteoglycans, biglycan and decorin, are present in extracellular matrices of skin, tendon, ligament, and cartilage. We investigated the effects of biglycan and decorin on the inhibition of alpha-thrombin by the serine proteinase inhibitor heparin cofactor II. In solution, heparin cofactor II inhibition of thrombin is accelerated by intact biglycan or decorin and by the dermatan sulfate-containing glycosaminoglycan (GAG) chains prepared from the proteoglycans, while core protein from cartilage biglycan had no effect. L-Iduronic acid-rich skin decorin and GAG chains had a greater accelerating effect than proteoglycan and GAG chains from cartilage that had lower L-iduronic acid content. Treatment of skin decorin and GAG chains with chondroitinase ABC totally eliminated the ability of these compounds to accelerate thrombin inhibition by heparin cofactor II suggesting that dermatan sulfate was responsible for this action. Both biglycan and decorin bound to type V collagen in a saturable and specific manner. Biglycan, decorin, and core protein from biglycan competed for decorin binding to the type V collagen, while only the intact proteoglycans competed for biglycan binding. When bound to type V collagen, both biglycan and decorin accelerated the heparin cofactor II/thrombin inhibition reaction as efficiently as the proteoglycans in solution. Our results demonstrate that heparin cofactor II in the presence of biglycan or decorin bound to type V collagen provides a "thromboresistant surface," further suggesting a physiological function for these proteins in regulating the extravascular activities of thrombin. PMID- 8440687 TI - A fluorescence anisotropy study of tetramer-dimer equilibrium of lambda repressor and its implication for function. AB - Tetramer-dimer equilibrium of lambda repressor has been studied by fluorescence anisotropy techniques. We have chosen 1-dimethylamino naphthalene-5-sulfonyl chloride (dansyl chloride)-labeled repressor to study the dissociation association equilibrium, because of relatively long life-time of the probe (> 10 ns). Polarization of the dansyl-labeled repressor decreases with decreasing protein concentrations in the range of 20 to 0.2 microM. The decrease of anisotropy was shown to be due to reversible dissociation of the protein. Size exclusion high-performance liquid chromatography studies and polyacrylamide gel electrophoresis under native conditions (Ferguson plot) confirmed that at around 20 microM concentrations the repressor exists in predominantly tetrameric form, whereas in lower concentrations it exists in predominantly dimer form. A dissociation constant of 2.3 +/- 0.9 microM was estimated in 0.1 M potassium phosphate, pH 8.0, at 25 degrees C. A stoichiometric amount of isolated single operator shifted the tetramer-dimer equilibrium toward the dimer. Increased ionic strength had only a modest effect on the dissociation constant. The thermodynamic constants for the dissociation reaction calculated from the Van't Hoff plot was +26.6 kcal/mol for delta H and +64.7 e.u. for delta S. The rotational correlation times derived from isothermal Perrin plot indicated elongated dimers and tetramers. PMID- 8440686 TI - Protein folding in a cell-free translation system. The fate of the precursor to mitochondrial aspartate aminotransferase. AB - The precursor to rat mitochondrial aspartate aminotransferase (pmAspAT) can be expressed in and purified from Escherichia coli as a fully active enzyme with remarkable trypsin resistance. Only two sites within the presequence are readily hydrolyzed (Martinez-Carrion, M., Altieri, F., Iriarte, A., Mattingly, J. R., Youssef, J., and Wu, T. (1990) Ann. N.Y. Acad. Sci. 585, 346-356). In contrast, pmAspAT freshly synthesized in rabbit reticulocyte lysate is significantly less resistant to proteolysis and is completely digested by trypsin. Extended incubation of the pmAspAT translation product slowly converts it to a species with qualitatively the same trypsin resistance as the purified pmAspAT. In addition, this species binds pyridoxal 5'-phosphate, exhibits catalytic activity, and loses its ability to be imported into mitochondria. This process appears to reflect protein folding. The rate of folding is unaffected by the addition of cofactor or the depletion of endogenous cofactor and is not significantly affected by the concentration of translation product in the reaction. Agents that decrease the availability of ATP partially inhibit the folding, whereas the sulfhydryl alkylating reagent N-ethylmaleimide and the detergent Triton X-100 completely prevent the conversion. Although the folding of pmAspAT in reticulocyte lysate is slow, folding is rapid once the translation product is sequestered within the mitochondria as the mature form of the enzyme. These results are presented as a model for the in vivo folding of pyridoxal-dependent, oligomeric mitochondrial precursors in the presence of cytoplasmic components and for the fate of true mitochondrial precursor proteins when not imported. PMID- 8440689 TI - Evidence for the presence of a phosphatidylcholine translocator in isolated rat liver canalicular plasma membrane vesicles. AB - In the present study we used the water-soluble short chain phosphatidylcholine analogue L-alpha-dibutyryl-glycero-3-phosphatidylcholine (diC4PC) to investigate the mechanism involved in the canalicular secretion of phospholipids in rat liver. Uptake of 14C-labeled di-C4PC was studied in isolated microsomes as well as in basolateral (sinusoidal) and canalicular plasma membrane vesicles. Saturable uptake of diC4PC into an osmotically active space was observed in microsomes and canalicular membrane vesicles. In contrast, diC4PC uptake into basolateral membrane vesicles could be accounted for by cross-contamination with endoplasmic reticulum and canalicular membrane vesicles. Whereas the Km values for diC4PC uptake (37 degrees C) were similar in microsomes (7.4 +/- 2.6 mM) and canalicular membrane vesicles (8.2 +/- 2.0 mM), the Vmax values were approximately 2-fold higher in canalicular membrane vesicles (29.6 +/- 2.7 nmol/mg of protein x min) than in microsomes (16.7 +/- 2.1 nmol/mg of protein x min). Furthermore, Pronase treatment of the membrane vesicles reduced diC4PC uptake by 34-54% in both subfractions, whereas the D-[14C]glucose-accessible water space was only reduced by approximately 20%. These data provide direct evidence for the presence of a protein-mediated phosphatidylcholine translocating activity in the canalicular membrane of rat hepatocytes. This canalicular "flippase" has kinetic properties similar to those described previously in microsomes and provides a potential pathway for the translocation of bile salt dissolvable biliary phospholipids to the exoplasmic leaflet of the canalicular membrane. PMID- 8440688 TI - Transcriptional regulation of G-protein alpha i subunit genes in LLC-PK1 renal cells and characterization of the porcine G alpha 1-3 gene promoter. AB - Heterotrimeric guanine nucleotide-binding proteins (G-proteins) function as signal transducers for a variety of hormone-coupled enzyme and ion transport systems in eukaryotic cells. The expression of pertussis toxin-sensitive G proteins (Gi) which couple their cognate receptors and effectors are regulated by cell cycle-dependent events in porcine LLC-PK1 renal epithelial cells. G alpha i 2 and G alpha i-3 isoforms are detected in these cells, and like G alpha i-2 (Holtzman, E. J., Soper, B. W., Stow, L. L., Ausiello, D. A., and Ercolani, L. (1991) J. Biol. Chem. 266, 1763-1771), we now demonstrate that G alpha i-3 mRNA and protein is coordinately expressed in these cells during differentiation. To gain further insights into these events, the porcine G alpha i-3 gene minimal promoter was characterized and found 67 base pairs upstream from the major transcription start site. The 56-base pair minimal promoter lacked TATAAA and GC boxes but did contain a sequence GGAAGTG conserved in both the human and porcine gene that could potentially bind an adenovirus E4TF1 transcription factor. In cells stably transfected with G alpha i-2 or G alpha i-3 gene 5'-flanking sequences fused to firefly luciferase cDNA reporter, temporal 10-15-fold transcriptional activation of both genes occurred before cellular polarization. Utilizing mobility shift assays which compared nuclear extracts from cells before and after cell polarization, a motif in the 5' region of the gene promoter GTACTTCCGCT was identified that bound an induced nuclear protein complex during transcriptional activation. In polarized cells complemented with the human glucocorticoid receptor, dexamethasone decreased G alpha i-2 but increased G alpha i-3 basal transcription and mRNA content 3-fold. These studies demonstrate that both G alpha i genes are dynamically regulated in LLC-PK1 cells by both growth, differentiation, and hormone signals. PMID- 8440690 TI - 13C nuclear magnetic resonance studies of malate and citrate synthesis and compartmentation in higher plant cells. AB - The synthesis of malate and citrate by sycamore cells (Acer pseudoplatanus L.) perfused with KH13CO3 was analyzed using 13C NMR. To perform in vivo experiments, cells were compressed in a 25-mm tube and perfused with an arrangement enabling tight control of the circulating nutrient medium. An original method using paramagnetic Mn2+ that induced a complete loss of the vacuolar malate and citrate signals was developed to discriminate between cytoplasmic and vacuolar pools of malate and citrate. Our results indicated the following. (a) The accumulation of appreciable amounts of malate in sycamore cells required rather high (1 mM) concentrations of bicarbonate at all the pH values tested. (b) Malate was equally labeled at C-1 and C-4, suggesting that malate labeled at C-1 was produced by randomization of C-1 and C-4 by mitochondrial fumarase. Indeed, the separation of the intact organelles from the lysed protoplasts indicated that fumarase activity was essentially limited to the mitochondria. Similarly, citrate was equally enriched at C-1 and C-5 + C-6 carboxyls. (c) Malate appeared first in the cytoplasmic compartment; and when a threshold of cytoplasmic malate concentration was attained, malate molecules were expelled into the vacuole, where they accumulated. On the other hand, citrate accumulated steadily in the vacuole. Pulse-chase experiments demonstrated the central role played by the tonoplast in governing the vacuolar influx of citrate and the permanent exchange of malate between the cytoplasm and the vacuole. PMID- 8440691 TI - Protein S binding to human endothelial cells is required for expression of cofactor activity for activated protein C. AB - An important feedback mechanism in blood coagulation is supplied by the protein C/protein S anticoagulant pathway. In this study we demonstrate that the binding of human protein S to cultured human umbilical vein endothelial cells (HUVECs) is required for the expression of cofactor activity of protein S toward factor Va inactivation by activated protein C (APC). The initial rate of endothelial cell mediated factor Va inactivation was 21.7 pM factor Va/50 pM APC min-1, which could be enhanced twice at a protein S concentration of 5 nM. This increase appeared to be specific for protein S because it could be inhibited by C4b binding protein and polyclonal antibodies against protein S. Furthermore, thrombin-cleaved protein S did not accelerate factor Va inactivation by APC on endothelial cells. The binding of 125I-protein S to endothelial cells was time dependent, specific, saturable, and required the presence of calcium ions. Scatchard analysis revealed (8.0 +/- 0.3) x 10(5) binding sites per cell with an apparent Kd of 24.4 +/- 2.2 nM. To study the physiological importance of the binding of protein S to human endothelial cells, seven monoclonal antibodies were examined for their ability to influence the protein S cofactor activity and binding capacity. Monoclonal antibodies directed against the gamma carboxyglutamic acid domain and the thrombin-sensitive region of protein S completely inhibited the protein S cofactor function in factor Va inactivation by APC on HUVECs. These monoclonal antibodies also inhibited 125I-protein S binding to HUVECs. Another monoclonal antibody, directed against an epitope on the third and/or fourth epidermal growth factor-like region, did not influence either protein S cofactor activity or binding of protein S to HUVECs. We conclude that binding of protein S to HUVECs is essential for the expression of its cofactor activity for APC. At least two regions in protein S, the gamma-carboxyglutamic acid domain and the thrombin-sensitive region, are involved in the expression of cofactor activity. PMID- 8440692 TI - Biosynthesis of platelet-activating factor (PAF) induced by chemotactic peptide is modulated at the lyso-PAF:acetyl-CoA acetyltransferase level by calcium transient and phosphatidic acid. AB - The chemotactic peptide fMLP (N-formyl-methionyl-leucyl-phenylalanine) induced the production of platelet-activating factor (PAF) by human polymorphonuclear leukocytes (PMN) incubated with cytochalasin B (CB). CoA-independent transacylase showed similar activity in both resting and stimulated PMN, and PAF production only occurred when lyso-PAF:acetyl-CoA acetyltransferase had been converted into the high activity form. PAF formation was coincidental with an increase of the concentration of cytosolic Ca2+ ([Ca2+]i), and with an enhanced formation of 1-O [3H]alkyl-2-acyl-sn-glycerol. Both fMLP-induced PAF production and the activation of lyso-PAF:acetyl-CoA acetyltransferase were diminished by propranolol. Since several molecular species of phosphatidic acid (PA) produced an inhibition of both PAF production and acetyltransferase activation on intact cells, a portion of the inhibitory effect of propranolol was related to the accumulation of PA. Furthermore, whereas CB increased both the extent and the duration of the fMLP induced [Ca2+]i transient, propranolol was found to inhibit the CB-induced increase of the [Ca2+]i transient. These data indicate that both the attenuation of [Ca2+]i transient and the accumulation of PA may operate as termination signals for PAF production by actin on lyso-PAF:acetyl-CoA acetyltransferase. PMID- 8440693 TI - The detection, purification, structural characterization, and metabolism of diphosphoinositol pentakisphosphate(s) and bisdiphosphoinositol tetrakisphosphate(s). AB - A new class of inositol phosphates containing energy-rich pyrophosphoryl residues has been characterized. D/L-1-Diphosphoinositol pentakisphosphate(s) and D/L-bis (1,4)-diphosphoinositol tetrakisphosphate(s) are present as soluble ionic species in the cytosol of amoebae (Dictyostelium discoideum) at concentrations in the range of 0.05-0.25 mM. These compounds are rapidly metabolized in intact cells and can be synthesized in cell lysates from myo-inositol hexakisphosphate in the presence of ATP. Their phosphomonoester groups have predicted C-O-P bond energies of between 3.3 and 4 kcal mol-1; however, the bond energies of the P-O-P links in their diphosphate moieties are 6.6 kcal mol-1 and hence similar to the equivalent bonds in ADP, indicating a potential role for these compounds as phosphate donors in phosphotransferase reactions. Compounds with similar chromatographic properties are found in a variety of mammalian cell types. PMID- 8440694 TI - Inhibitory action of 4-aminopyridine on Ca(2+)-ATPase of the mammalian sarcoplasmic reticulum. AB - In the isolated guinea pig diaphragm muscle, 4-aminopyridine (4-AP) elicited a marked potentiation of twitch contraction evoked by direct electrical stimuli. Although tetraethylammonium (TEA) and charybdotoxin only slightly potentiated twitch contraction, 4-AP, but not TEA, also augmented a contractile response to caffeine. These effects of 4-AP on muscle contraction could not be interpreted by a simple inhibition of potassium channels on the plasma membrane. In the fragmented sarcoplasmic reticulum (SR) prepared from the guinea pig psoas muscle, 4-AP inhibited the ATP-driven Ca2+ uptake from the extravesicular medium. Furthermore, 4-AP at concentrations less than 10 mM elicited a selective inhibition of Ca(2+)-activated SR ATPase in a competitive manner against the Ca2+ concentration of the medium and 10 mM 4-AP showed the unsurmountable inhibition. 4-AP at 30 mM apparently inhibited activities of other ATPases such as Na+,K+- and myosin ATPases. In contrast, other potassium channel blockers such as TEA, apamin, charybdotoxin, and glibenclamide did not inhibit the SR function. These results suggest that, although the specific concentration range is rather small, 4-AP elicits an inhibition of SR Ca(2+)-pumping activity, leading to the marked potentiation of muscle contractile responses to electrical stimuli and caffeine. PMID- 8440695 TI - Human plasma phospholipid transfer protein causes high density lipoprotein conversion. AB - The effect of human plasma phospholipid transfer protein (PLTP) on the particle size distribution of human high density lipoprotein (HDL) was studied by incubating human HDL3 (particle diameter, 8.7 nm) together with PLTP in vitro. Incubation of HDL3 with highly purified preparations of PLTP, devoid of cholesterol ester transfer protein (CETP), induced a conversion of the homogenous population of HDL particles into two main populations of particles, one larger, particle diameter 10.9 nm, and one smaller, particle diameter 7.8 nm, than the original HDL3. These size changes were evident as analyzed by gradient gel electrophoresis and by high resolution gel filtration. The degree of the conversion was dependent on the amount of PLTP added to the incubation and on incubation time. An inhibitory monoclonal antibody (TP-1) directed against CETP had no effect on the HDL conversion. The PLTP used was purified to homogeneity from human plasma using ultracentrifugation and a combination of hydrophobic, cation-exchange, heparin-Sepharose-, anion-exchange, and gel filtration chromatographies. The monoclonal anti-CETP antibody (TP-1), which inhibits lipid transfer catalyzed by CETP, did not react with PLTP or inhibit its activity. The estimated molecular weight of PLTP is 75,000. The present study demonstrates that PLTP can act like the putative conversion factor and has the ability to convert HDL3 into populations of larger and smaller HDL particles. The mechanism(s) involved in this process and its physiological relevance remain to be established. PMID- 8440696 TI - The transit sequence mediates the specific interaction of the precursor of ferredoxin with chloroplast envelope membrane lipids. AB - The interaction of the precursor of the chloroplast protein ferredoxin with membrane lipids was studied in monolayer experiments in order to investigate the possible involvement of membrane lipids in the protein translocation process. The precursor efficiently and specifically inserts into a total lipid extract of its biological target the outer envelope membrane of chloroplasts. This interaction is mediated by the transit sequence as it can also be observed for the chemically prepared transit peptide of ferredoxin but neither for the ferredoxin apoprotein nor holoprotein. Interactions with the individual chloroplast lipids, monogalactosyl-diacylglycerol, sulfoquinovosyl-diacylglycerol, and phosphatidylglycerol are predominantly involved which corresponds to the results obtained for transit peptide fragments of the small subunit of ribulose-1,5 bisphosphate carboxylase/oxygenase (van't Hof, R., Demel, R. A., Keegstra, K., and De Kruijff, B. (1991) FEBS Lett. 291, 350-354). No efficient interaction was obtained with digalactosyl-diacylglycerol and phosphatidylcholine, suggesting that a loose lipid headgroup packing due to small lipid headgroups and/or electrostatic repulsions facilitates efficient insertion. The observed preferences for interaction of the precursor and transit peptide of ferredoxin for the chloroplast outer envelope membrane lipid extract and the presequence of cytochrome c oxidase subunit IV for the mitochondrial outer membrane lipid extract indicate that targeting sequence-lipid interactions contribute to organelle-specific protein targeting. PMID- 8440697 TI - Identification of productive folding intermediates which account for the flow of protein folding pathway. AB - Reduced hirudin N-terminal fragment (Hir1-27, 4 cysteines) refolds to form two disulfide structures. The isomer containing the native disulfide prevailed as the predominant product. The disulfide folding pathway was elucidated by trapping the intermediates with acid (4% trifluoroacetic acid). All six possible one-disulfide intermediates were detected to exist in equilibrium with molar ratio of approximately 1:1:1:0.4:0.4:0.18. These intermediates were purified and structurally characterized. They were also allowed to resume the folding by reconstituting into alkaline buffer in order to evaluate the productivity of individual intermediate along the pathway. These results demonstrate that the most productive intermediate that specifies the pathway flow is neither a well populated species nor the one that contains the native disulfides. PMID- 8440698 TI - Purification of a mammalian protein geranylgeranyltransferase. Formation and catalytic properties of an enzyme-geranylgeranyl pyrophosphate complex. AB - A protein geranylgeranyltransferase (PGGT) that transfers the geranylgeranyl group from geranylgeranyl pyrophosphate (GGPP) to the cysteine residue in the C terminal sequence Cys-Ali-Ali-Leu (Ali is an aliphatic amino acid) of proteins and peptides has been purified to apparent homogeneity from bovine brain. This was accomplished by affinity chromatography of partially purified enzyme on a gel containing a covalently attached hexapeptide SSCILL. This peptide was identified as a tight-binding ligand of the PGGT by employing a semi-random peptide synthetic strategy. The purified enzyme consists of two subunits of apparent molecular mass 40 and 48 kDa. Affinity-purified PGGT effectively catalyzes the prenylation of peptides that contain a C-terminal Leu or Phe residue. The PGGT forms a stable binary complex with intact GGPP that can be isolated by gel filtration. Addition of a peptide substrate to this complex results in the quantitative transfer of the prenyl group to the peptide. This transfer occurs without the equilibration of enzyme-bound GGPP with free GGPP. When the PGGT was incubated with farnesyl pyrophosphate, the amount of binary complex formed was about 25% of that formed with GGPP. PMID- 8440699 TI - Transcriptional regulation of a hematopoietic proteoglycan core protein gene during hematopoiesis. AB - The expression of a hematopoietic proteoglycan core protein (HpPG) gene is up regulated during the early stages of myeloblast differentiation at a time point coinciding with the beginning of granule genesis (Stellrecht, C. M., Mars, W. M., Miwa, H., Beran, M., and Saunders, G. F. (1991) Differentiation 48, 127-135). The mechanism of this up-regulatory event was investigated by analyzing the expression and regulation of the HpPG gene during the differentiation of the pluripotent hematopoietic cell line, K562. The level of HpPG gene expression in these cells was up-regulated approximately 10-fold upon 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced megakaryocytic differentiation, as measured by Northern blot analysis. The HpPG gene's expression remained relatively unchanged during hemin-induced erythroid differentiation, further demonstrating the specificity of this regulatory event for granule-producing cell lineages. The effect of TPA induction on HpPG gene expression was also assessed during the differentiation of the myeloid leukemia cell line, HL-60. The expression of the gene was down regulated approximately 20-fold upon TPA-induced differentiation into macrophage like cells. In contrast, only a minimal decrease in HpPG gene expression was detected in gamma-interferon-induced monocyte differentiation. No detectable changes in expression levels were seen in HL-60 cells differentiated into granulocytes with retinoic acid or dimethyl sulfoxide. Nuclear runoff analysis demonstrated that the regulation of the HpPG gene is under transcriptional control in both TPA-induced differentiation systems. PMID- 8440700 TI - Insulin receptor autophosphorylation occurs asymmetrically. AB - The unoccupied insulin receptor is a structurally symmetric, disulfide-linked dimer, comprising two alpha beta halves, each with a potential insulin binding alpha subunit and a kinase active beta subunit. In the accompanying paper (Shoelson, S. E., Lee, J., Lynch, C. S., Backer, J. M., and Pilch, P. F. (1993) J. Biol. Chem. 268, 4085-4091), we described the utility of a novel insulin analogue, L-benzoylphenylalanineB25,B29 epsilon-biotin insulin (BBpa insulin)1 as a probe for receptor behavior, and we determined that binding and cross-linking of one BBpa insulin molecule could fully stimulate insulin receptor autophosphorylation. Here we use this analogue to determine the symmetry of the autophosphorylation reaction. The alpha beta half-receptor that does not covalently couple to BBpa insulin incorporates 50% more orthophosphate than the alpha beta half that becomes coupled to the insulin analogue. Phosphopeptide mapping of each receptor half shows minimal differences in the phosphorylation sites or their relative contribution to the phosphate content of each half. The kinetics of 32P incorporation into each receptor half are essentially identical over a 10-20-min time course. Phosphopeptide mapping analysis reveals that the phosphate incorporation patterns do not change between the two alpha beta half receptor forms (BBpa insulin-linked and unlinked, respectively) at different time points or concentrations of ATP ranging from 12 to 200 microM. Based on these and other data, we propose a model of insulin receptor activation whereby binding of one insulin molecule can trigger autophosphorylation in an asymmetric fashion. PMID- 8440701 TI - Features of calmodulin that are important in the activation of the catalytic subunit of phosphorylase kinase. AB - Calmodulin (CaM) is an integral subunit, called delta, of the phosphorylase kinase hexadecamer, and the activity of the isolated catalytic gamma-subunit of the kinase is stimulated by CaM. We report here the first analysis of functionally important features of CaM for activation of the gamma-subunit. A set of genetically engineered CaMs, in which acidic residues in each of the four E helices of the "EF-hands" were changed to basic lysine residues, was used to probe the relative importance of charge features in each domain of CaM. The maximal activation of the isolated gamma-subunit was diminished by all of the charge reversal mutations. The gamma-subunit was especially sensitive to reversals in the second and third E-helix of CaM (residues 45-47 and 82-84), the latter being present in the central helix. The results suggest the functional importance of electrostatics in the interactions between the delta-subunit (CaM) and the catalytic gamma-subunit of phosphorylase kinase, which is similar to results obtained with CaM-dependent myosin light chain kinase (MLCK) from chicken gizzard and CaM-dependent protein kinase II (CaMPK-II). However, novel features of the interaction between CaM and the gamma-subunit of phosphorylase kinase are the significant contribution of electrostatics throughout the CaM molecule, including residues in both halves and on more than one face of CaM, and the lack of a major effect of the CaM mutations on substrate kinetic parameters, unlike the effects observed with MLCK and CaMPK-II. These results are consistent with a model in which the delta-subunit (CaM) of phosphorylase kinase interacts with an extended region or multiple regions of the gamma-subunit and suggest that the mechanism of CaM activation of the gamma-subunit may have features that are distinct from those of MLCK and CaMPK-II. PMID- 8440702 TI - On the reaction mechanism of phenol hydroxylase. New information obtained by correlation of fluorescence and absorbance stopped flow studies. AB - Steps in the hydroxylation pathway of the flavoprotein phenol hydroxylase with resorcinol as substrate have been studied by a combination of fluorescence and absorbance stopped flow techniques. In the presence of azide, a series of highly fluorescent oxygenated flavin intermediates has been observed, corresponding to those previously detected by absorbance measurements (Detmer, K., and Massey, V. (1985) J. Biol. Chem. 260, 5998-6005). In addition, yet another intermediate has been found as the immediate product of the reaction of the reduced enzyme with O2. This new species is non-fluorescent in the presence of azide, but fluorescent in the absence of monovalent anions and had escaped detection in previous absorbance studies because of the similarity in its rates of formation and conversion to the next intermediate and similarity in their spectra. These two early intermediates are tentatively identified as the anionic and protonated species of the flavin C4a-hydroperoxide or, alternatively, as two conformationally different forms of the enzyme hydroperoxide. The next intermediate, previously referred to as intermediate II, is also highly fluorescent and so is considered unlikely to be due to a complex of a flavin alkoxyl radical and a substituted cyclohexadienyl radical, as proposed by Anderson et al. (Anderson, R. F., Patel, K. B., and Stratford, M. R. L. (1990) J. Biol. Chem. 265, 1952-1957). The conversion of intermediate II to the next intermediate, intermediate III (the C4a-hydroxyflavin), is characterized by a large substrate deuterium isotope effect in the 320-390 nm range, but not by fluorescence or by absorbance at wavelengths > 400 nm. This is ascribed to dissociation from the enzyme of a cyclohexadienone product, leaving the enzyme in its C4a-hydroxyflavin form. The latter eliminates H2O to re-form oxidized flavin, but in a competing reaction, in the presence of excess substrate, forms a very stable complex, which decays orders of magnitude more slowly than the uncomplexed enzyme. PMID- 8440703 TI - The action of oxidized low density lipoprotein on calcium transients in isolated rabbit cardiomyocytes. AB - The effect of oxidized low density lipoprotein (oxLDL) on the Ca2+ transients of isolated rabbit cardiomyocytes was assessed. LDL was oxidized by a free radical generating system in vitro. The systolic Ca2+ concentration in transients was significantly increased after treatment with 100 micrograms of oxLDL cholesterol/ml for 16 min without having any effect on the diastolic [Ca2+]. However, a toxic effect was observed when the concentration of oxLDL was increased to 1,000 micrograms/ml. Cells treated with 100 micrograms of oxLDL/ml were more sensitive to the blocking action of nicardipine on the Ca2+ transient than were control cardiomyocytes. Furthermore, oxLDL failed to produce a stimulatory effect on the transient when the extracellular [Ca2+] was lowered. The malondialdehyde content in the oxLDL correlated well with the change in systolic [Ca2+] of treated cells. Lazaroid, a novel antioxidant, completely inhibited malondialdehyde formation in the oxLDL and prevented the increment of systolic [Ca2+] in the treated cells. The data indicate that oxLDL can induce relatively rapid alterations in cellular Ca2+ transients via a modification of Ca2+ entry through the L-type Ca2+ channel. LDL oxidation induced by free radicals may play an important role in influencing cardiac contractile function during pathological conditions such as ischemia/reperfusion challenge. PMID- 8440704 TI - Identification of non-cyclooxygenase-derived prostanoid (F2-isoprostane) metabolites in human urine and plasma. AB - Free radicals are thought to play an important role in many types of tissue injury. Recently, we reported that a series of prostaglandin F2-like compounds (F2-isoprostanes) capable of exerting potent biological activity are produced in vivo by free radical-induced lipid peroxidation. Their formation is independent of the cyclooxygenase enzyme and has been shown to increase profoundly in animal models of free radical injury and lipid peroxidation. We now report the identification of F-ring isoprostane metabolites in human urine and plasma utilizing a gas chromatographic/mass spectrometric assay for the major urinary metabolite of prostaglandin D2 (9 alpha,11 beta-dihydroxy-15-oxo-2,3, 18,19 tetranorprost-5-ene-1,20-dioic acid). Evidence confirming these metabolites as tetranor, dicarboxylic acid compounds containing one double bond, cis cyclopentane ring hydroxyls, and one keto group similar in structure to the major urinary metabolite of prostaglandin D2 was obtained by analysis of human urine by electron ionization mass spectrometry. Levels of these metabolites in normal human urine were determined and found to be unaffected by cyclooxygenase inhibitors. Evidence that these metabolites arise from F2-isoprostanes was obtained by demonstrating that (a) marked increases in plasma levels and urinary excretion of these metabolites, which were unaffected by coadministration of indomethacin, occurred in rats administered CCl4 to induce F2-isoprostane formation and (b) marked increases in levels of these metabolites in plasma and urine resulted from the intravenous infusion of F2-isoprostanes into a rat. Quantification of these isoprostane metabolites in urine and plasma may provide a reliable index of endogenous isoprostane production which could prove to be an important advance in our ability to assess oxidant stress in vivo in humans. PMID- 8440705 TI - Mitogen activation of resting lymphocytes exposes cryptic insulin receptors. AB - Mitogen activation of resting lymphocytes induces expression of high affinity insulin receptors on the plasma membrane. The mechanism underlying this effect on insulin receptor expression was examined by comparing levels of insulin receptor mRNA and protein in resting and mitogen-activated rodent lymphocytes. Analysis of RNA levels indicated that resting and concanavalin A-activated lymphocytes contained equivalent amounts of insulin receptor mRNA with predominant transcripts of 7.9 and 9.5 kilobases. Although little or no insulin binding was detectable on intact resting lymphocytes, detergent solubilization of these cells resulted in the appearance of readily detectable insulin binding activity that could be immunoprecipitated with anti-insulin receptor antibodies. Detergent solubilized resting and mitogen-activated lymphocytes expressed equivalent amounts of insulin receptors that bound insulin with similar affinity (KD = 90 pM) and migrated on reduced SDS-polyacrylamide gels with apparent masses of approximately 130 and approximately 95 kDa. Insulin receptors from resting lymphocytes appeared to be associated with the plasma membrane since 125I labeling of intact lymphocytes radiolabeled the insulin receptor, insulin binding activity was detected in membrane fractions of hypotonically lysed cells, and trypsin treatment of intact cells destroyed > 90% of the insulin binding activity in detergent extracts. These results suggest that resting lymphocytes express insulin receptor mRNA and protein and that mitogen activation exposes cryptic insulin receptors present in the plasma membrane of resting lymphocytes. PMID- 8440706 TI - Location of the human red cell spectrin tetramer binding site and detection of a related "closed" hairpin loop dimer using proteolytic footprinting. AB - Head-to-head association of two spectrin alpha beta heterodimers to form tetramers involves the formation of two equivalent alpha-beta complexes. The sites on the alpha subunit N-terminal region and beta subunit C-terminal region that form these alpha beta complexes have been identified using protease footprinting and direct binding assays. The existence of a similar previously hypothesized internal head-to-head alpha beta interaction in dimers was also demonstrated. The discrete regions of both subunits that are protected from proteolysis in tetramers and dimers are not due to the laterally associated subunit since head-to-head complexes of a univalent alpha peptide with a univalent beta peptide show similar protection of the same sites. These sites are unshielded immediately after monomers assemble side-to-side to form heterodimers, demonstrating that reconstituted dimers are initially in an "open" conformation. Conversion of open dimers to a closed form through formation of the internal head to-head alpha beta association, as demonstrated by restoration of protease protection, occurred on a time scale of hours at 0 degrees C. Analysis of peptide binding affinities as well as isolation and sequence analysis of head-to-head alpha beta noncovalent complexes further defined the regions required for association on both subunits. These regions are homologous to the 106-residue repetitive motif that comprises most of both chains. An algorithm designed to improve prediction accuracy of multiple homologous motifs was used to model the conformation of spectrin repetitive motifs as well as the contact regions. In this model, the separate alpha and beta binding sites are incomplete complementary parts of a triple stranded folding unit. Formation of the alpha beta head-to-head complex produces a triple stranded conformational unit that is slightly different from other homologous motifs in the protein. Most hemolytic anemia mutations that are known to disrupt tetramer association are located in the mapped regions, including several mutations that induce a conformational change in the paired subunit. PMID- 8440707 TI - Interleukin 1 and tumor necrosis factor stimulate two novel protein kinases that phosphorylate the heat shock protein hsp27 and beta-casein. AB - We have partially purified and characterized two protein kinases that were strongly activated by interleukin-1 (IL-1) or tumor necrosis factor (TNF) in MRC 5 fibroblasts. The kinases were separated by anion exchange chromatography of cytosolic fractions. They phosphorylated in vitro the small heat shock protein (hsp27) or beta-casein and were stimulated 3- and 4.5-fold, respectively, in cells that had been exposed to IL-1 or TNF for 10 min. They were distinct from the mitogen-activated protein kinases, whose activation by IL-1 or TNF has been reported recently. The hsp27 kinase phosphorylated its substrate on serine residues. Its molecular mass was estimated to be 45-kDa by gel filtration. It is probably involved in the increase in hsp27 phosphorylation seen in intact cells. The beta-casein kinase behaved as a 65-kDa protein. It phosphorylated its substrate on serine and threonine residues and had little activity on alpha casein. The hsp27 and beta-casein kinases were not activated after stimulation of the cells with phorbol myristate acetate (PMA). In contrast, the MAP kinases were activated to a similar extent (2-3-fold) by the cytokines and by PMA. The hsp27- and beta-casein kinases probably correspond to novel enzymes whose mechanisms of activation may be independent of protein kinase C or MAP kinases. PMID- 8440708 TI - Inhibition of the tyrosine kinase activity of the fibroblast growth factor receptor by the methyltransferase inhibitor 5'-methylthioadenosine. AB - Stimulation of fibroblasts with basic fibroblast growth factor (bFGF) led to the rapid tyrosine phosphorylation of a number of cellular proteins, including a major substrate of 90 kDa. The methyltransferase inhibitor 5'-methylthioadenosine (MTA) was found to be a specific inhibitor of bFGF-stimulated protein tyrosine phosphorylation in fibroblasts, blocking both receptor autophosphorylation and substrate phosphorylation. MTA had no effect on either epidermal growth factor- or platelet-derived growth factor-stimulated protein tyrosine phosphorylation in fibroblasts. MTA also inhibited both bFGF-stimulated protein tyrosine phosphorylation and neurite outgrowth in PC12 cells. MTA was a specific inhibitor of bFGF-stimulated protein tyrosine phosphorylation only in intact cells. MTA delayed and reduced, but did not inhibit, bFGF internalization and processing. The effects of MTA on bFGF-stimulated tyrosine phosphorylation required only a brief pretreatment with the agent and were readily reversible. PMID- 8440709 TI - The hepatic interleukin-6 receptor. Studies on its structure and regulation by phorbol 12-myristate 13-acetate-dexamethasone. AB - Recombinant human 125I-interleukin-6 (IL-6) was cross-linked with the homobifunctional reagent disuccinimidyl suberate to human hepatoma cells (HepG2). Three recombinant human 125I-IL-6-containing complexes of apparent molecular masses of 100, 120, and 200 kDa were immunoprecipitated with specific antibodies to human IL-6 or to the 80-kDa IL-6 receptor subunit. We show by immunoprecipitation, peptide mapping, and by the use of a cleavable heterobifunctional cross-linker (Denny-Jaffe reagent) that different polypeptides are involved in the formation of the 100- and 120-kDa IL-6-containing complexes. The molecular compositions of the 100- and 120-kDa cross-linked complexes were identified. The 100-kDa complex consisted of one ligand and one IL-6 receptor subunit, glycoprotein 80 (gp80), whereas the 120-kDa complex was found to be composed of one ligand and a polypeptide which was immunoprecipitable with the monoclonal antibody AM64 directed against gp130. Exposure of HepG2 cells to phorbol 12-myristate 13-acetate (PMA) or PMA-dexamethasone led to an increase in the 80-kDa IL-6 receptor mRNA and functional receptor protein. Whereas treatment of HepG2 cells with PMA led to an increase in the formation of gp80.gp130.IL-6 complexes determined by cross-linking, no corresponding increase in high affinity binding sites was found. The existence of a third IL-6 receptor subunit present in limiting amounts on HepG2 cells is proposed to explain this discrepancy. Evidence is presented that the 80-kDa IL-6 receptor up-regulation by PMA dexamethasone is caused by the depletion of protein kinase C since the protein kinase C inhibitor staurosporine mimics the effect of PMA-dexamethasone. PMID- 8440710 TI - Isolation and characterization of a novel member of the gene family encoding the cAMP response element-binding protein CRE-BP1. AB - Among multiple CRE (cyclic AMP response element)-binding proteins, CRE-BP1 (also designated ATF-2) has two unique characteristics: it mediates the adenovirus E1A induced trans-activation and forms a heterodimer with c-Jun. Two structures, a putative metal finger and a leucine zipper, in CRE-BP1 are responsible for these capacities. As a new member of a CRE-BP1 family that has similar metal finger and leucine zipper structures, we have isolated cDNA clones of CRE-BPa by cross hybridization with CRE-BP1 cDNA. CRE-BPa protein consists of 508 amino acids and has a molecular weight of 56,840. CRE-BPa protein is highly homologous with CRE BP1 in four regions: two of them are the regions containing the putative metal finger or the DNA-binding domain consisting of the basic amino acid cluster and the leucine zipper. Like CRE-BP1, CRE-BPa binds to CRE with higher affinity than to the 12-O-tetradecanoylphorbol-13-acetate response element as a homodimer or a CRE-BPa/c-Jun or CRE-BPa/CRE-BP1 heterodimer. However, using the c-Myb-CRE-BPa fusion protein, it was show that CRE-BPa could not mediate the E1A-induced trans activation. Expression of CRE-BPa mRNA was found in a limited number of cell lines, and multiple sizes of CRE-BPa mRNA species were detected in some cell lines and tissues. CRE-BPa will be useful to clarify the mechanism of CRE mediated transcriptional activation by E1A or c-Jun. PMID- 8440711 TI - The biosynthesis of the subtilisin-related proprotein convertase PC3, but no that of the PC2 convertase, is regulated by glucose in parallel to proinsulin biosynthesis in rat pancreatic islets. AB - The biosynthesis of proinsulin is specifically stimulated by glucose in the pancreatic beta-cell, and this, in turn, places an increased demand on the mechanism for proinsulin to insulin conversion. Proteolytic proinsulin processing is catalyzed by two endopeptidases putatively identified as the subtilisin related PC2 and PC3 convertases (Bennett, D. L., Bailyes, E. M., Nielson, E., Guest, P. C., Rutherford, N. G., Arden, S. D., and Hutton, J. C. (1992) J. Biol. Chem. 267, 15229-15236; Bailyes, E. M., Shennan, K. I. J., Seal, A. J., Smeekens, S. P., Steiner, D. F., Hutton, J. C., and Docherty, K. (1992) Biochem. J. 285, 391-394). In this study, we demonstrate in isolated rat pancreatic islets that the biosynthesis of PC3 was specifically stimulated by glucose relatively parallel to that of proinsulin. In contrast, however, PC2 biosynthesis was not glucose-regulated. The stimulation of PC3 and proinsulin biosynthesis was observed above a threshold of 4 mM glucose and reached a maximum (about 7-10 fold) above 10 mM glucose concentrations. Glucose stimulation for PC3 and proinsulin biosynthesis was rapid (occurring within 20 min and reaching a maximum by 60 min) and was not affected by the additional presence of actinomycin D, suggesting regulation predominantly at the translational level. Moreover, the intracellular signals for glucose-stimulated PC3 and proinsulin biosynthesis appeared to be similar, requiring the metabolism of glucose. PC3 has been implicated as the key endopeptidase in proinsulin to insulin conversion, in that it is the enzyme which preferentially initiates the process (Rhodes, C. J., Lincoln, B., and Shoelson, S. E. (1992) J. Biol. Chem. 267, 22719-22727). We suggest that co-ordinate stimulation of PC3 biosynthesis, along with that of its proinsulin substrate, elucidates an additional control point by which the mechanism of proprotein processing might be regulated. PMID- 8440712 TI - Use of Escherichia coli strains containing fad mutations plus a triple plasmid expression system to study the import of myristate, its activation by Saccharomyces cerevisiae acyl-CoA synthetase, and its utilization by S. cerevisiae myristoyl-CoA:protein N-myristoyltransferase. AB - A system is described for studying protein N-myristoylation, a eukaryotic protein modification, in Escherichia coli strains containing components of eukaryotic metabolic pathways that regulate metabolism of myristoyl-CoA:protein N myristoyltransferase (Nmt1p) substrates. Three recombinant plasmids were used to simultaneously direct synthesis of Saccharomyces cerevisiae Nmt1p, a substrate protein (S. cerevisiae ADP-ribosylation factor 1, Arf1p), and one of the acyl-CoA synthetases produced by S. cerevisiae (Faa1p) in isogenic strains of bacteria with wild type or mutant alleles of genes comprising the regulon for fatty acid degradation (FadR, FadE, FadL and FadD). Incorporation of exogenous tritiated myristate into Arf1p and bacterial phospholipid biosynthetic pathways was analyzed. Removal of FadL, a 448-residue protein necessary for efficient transport of fatty acids across the outer membrane, had no detectable effect on Nmt1p-dependent N-myristoylation of Arf1p. This finding is consistent with the notion that permeation of C14:0 across the bacterial inner membrane can occur by simple diffusion. Studies of strains that contain a mutation in FadE which inhibits beta-oxidation of exogenous fatty acids, confirm that Nmt1p retains its specificity for myristoyl-CoA over palmitoyl-CoA in E. coli. A mutation that inactivates FadD, a 580-residue protein which is the only acyl-CoA synthetase produced by this bacterium, completely blocks incorporation of exogenous myristate into Arf1p. This failure to be incorporated indicates that myristoyl acyl carrier protein, generated by inner membrane acyl-acyl carrier protein synthetase, is not a substrate for Nmt1p. S. cerevisiae Faa1p can partially complement this mutant fadD allele. It can fully "restore" N-myristoylation of Arf1p. Faa1p can also rescue growth at 37 degrees C of fadD- strains on minimal media supplemented with C12:0, although this rescue becomes less efficient as the chain length of the supplemental fatty acid increases. In addition, S. cerevisiae Faa1p is better able to direct myristoyl-CoA to the bacteria's phospholipid biosynthetic pathways than FadD, while FadD is more efficient at directing myristoyl-CoA to the genetically engineered protein N-myristoylation pathway. Since cellular acyl-CoA synthetase activity in S. cerevisiae has been distributed to at least two functionally differentiated proteins, this system should be useful for comparing their structure-activity relationships as well as their interactions with Nmt1p in an organelle-free environment. PMID- 8440713 TI - Identification and purification of a calcium-binding protein in hepatic nuclear membranes. AB - Recent evidence suggests that nuclei possess Ca2+ transport mechanisms to regulate nucleoplasmic/cytosolic Ca2+ gradients. We, therefore, investigated the possibility that Ca(2+)-binding proteins may also exist within the nucleus. Electrophoretic analysis revealed the presence of an acidic 93-kDa protein (p93) in the membranes of isolated nuclei. p93 stained blue with "Stains-All" in SDS polyacrylamide gels and was the major 45Ca(2+)- and ruthenium red-binding nuclear envelope protein in electroblot overlays. p93 was resistant to extraction by 6 M urea but was solubilized in 2% Triton X-100. Citric acid was highly effective in removing the outer nuclear membrane (ER) with concomitant reduction (< 10-fold) of mannose-6-phosphatase activity, but not p93. 45Ca(2+)-binding assays of purified p93 revealed the presence of high capacity Ca(2+)-binding sites comparable to calreticulin. This evidence strongly suggests that p93 is a major Ca(2+)-binding protein of the inner nuclear envelope membrane. Partial amino acid sequence analysis revealed that p93 was close to 100% homologous with a recently identified ER Ca(2+)-binding protein known as calnexin. It is likely, therefore, that p93 is calnexin. However, mild CHAPS detergent treatment of nuclear envelopes and ER revealed distinctly different solubility properties of each membrane for the extraction of p93. This, together with the citrate data, strongly suggests that p93/calnexin, in isolated nuclear envelopes, is mostly bound to the inner membrane. It is possible that p93 may be involved with the regulation of Ca2+ transients between the nucleoplasm and perinuclear space. PMID- 8440714 TI - Biosynthesis of locust lipophorin. Apolipophorins I and II originate from a common precursor. AB - Biosynthesis of apolipophorins of high density lipophorin of the locust Locusta migratoria was studied in vitro. Analysis of immunoprecipitates from homogenates of in vitro labeled fat body revealed a common precursor for apolipophorin I (apoLp-I, M(r) 220,000) and apolipophorin II (apoLp-II, M(r) 72,000) with a molecular mass of approximately 280 kDa. Pulsechase experiments showed that this high molecular mass precursor is cleaved into apoLp-I and apoLp-II which subsequently are secreted as high density lipophorin from the fat body. The time required for the complete synthesis and secretion was estimated to be approximately 35 min. Both apolipophorins are glycoproteins as demonstrated by the incorporation of [3H]mannose. Treatment of [3H]mannose-labeled apolipophorin with endoglycosidase H resulted in the complete removal of the incorporated [3H]mannose. Endoglycosidase H treatment of [3H]leucine-labeled apolipophorins caused a reduction in molecular mass of approximately 3 kDa for apoLp-I and 3.5 kDa for apoLp-II, suggesting the N-linked carbohydrate content to be 1-2 and 5%, respectively. Incubation of fat body tissue in the presence of low concentrations of tunicamycin led to the synthesis and release of nonglycosylated apolipophorins. PMID- 8440715 TI - Characterization of a novel bacterial adhesion specificity of Streptococcus suis recognizing blood group P receptor oligosaccharides. AB - Streptococcus suis causes sepsis, meningitis, and other serious infections in piglets, and meningitis in humans. Hemagglutination inhibition experiments with mono- and oligosaccharides and glycoproteins indicated that galactose-binding strains of S. suis recognized the Gal alpha 1-4Gal sequence present in the P1 and Pk blood group antigen structures. In thin-layer chromatography overlay assays the bacteria bound to trihexosylceramide (GbO3) but not to globoside (GbO4) or Forssman glycolipid (GbO5), in contrast to P-fimbriated Escherichia coli, which bound only to the latter two. The S. suis adhesin also differed from that of E. coli in that some of the hydrogen bonds formed with the receptor, as determined with chemically modified receptor analogues, were different. In agreement with the binding specificity, the S. suis bacteria agglutinated best among P blood group erythrocytes those of the P1k and P2k type, and from different animal erythrocytes those from rabbit, which express GbO3 as the predominant glycolipid. Binding to frozen sections of pig pharyngeal tissue was decreased by the free GbO3 oligosaccharide and its protein conjugate, which indicated that the corresponding glycolipid may function as receptor for galactose-binding strains of S. suis in pig pharyngeal epithelium. PMID- 8440716 TI - Organization of the human gene encoding the cytoskeletal protein vinculin and the sequence of the vinculin promoter. AB - The human vinculin gene contains 22 exons ranging in size from 71 base pairs (bp) to 303 bp (average 155 bp) with the exception of exon 22 which contains 144 bp of coding sequence and 1848 bp of 3'-untranslated sequence including two polyadenylation signals. There is a limited correlation between exon boundaries and functional domains within the vinculin molecule. The talin-binding domain in vinculin spans residues 1-258, and the first 6 exons encode residues 1-261. Similarly, the predicted boundaries of the central repeat domain (residues 259 589) are close to the boundaries of exons 7 and 12. Analysis of vinculin mRNAs in human uterus showed that alternative splicing of the gene is limited to exon 19, which encodes the 68 amino acids included in the muscle-specific isoform called metavinculin. We have determined 1.1 kilobases of sequence 5' of the transcription start site. The vinculin promoter lacks a TATA box, but does contain six Sp1 sites, and a CArG box at position -262 which forms the core of the serum response element found in immediate-early response genes. Expression of a vinculin promoter/CAT construct is serum-inducible in NIH3T3 cells demonstrating that the promoter does contain a functional serum response element. PMID- 8440717 TI - Cloning and active site mutagenesis of Vibrio cholerae DsbA, a periplasmic enzyme that catalyzes disulfide bond formation. AB - Recently, a gene (dsbA) involved in the biogenesis of secreted oligomeric enterotoxins in Vibrio cholerae was described, which encodes an exported protein possessing a -Cys-Pro-His-Cys- motif similar to that found in the active sites of eukaryotic and prokaryotic thiol-disulfide oxidoreductases (Yu, J., Webb, H., and Hirst, T. R (1992) Mol. Microbiol. 6, 1949-1958). Here, we report the cloning of the dsbA gene of V. cholerae and the demonstration that the encoded periphlasmic enzyme has disulfide isomerase-like activity. Oligonucleotide-directed mutagenesis of either of the 2 Cys residues to Ala in the putative active site of DsbA abolished both its isomerase activity and its capacity to promote enterotoxin biogenesis. We conclude that the Cys residues constitute the active site domain of DsbA and are essential for its activity in vivo and in vitro. PMID- 8440718 TI - Transgenic analysis of the thyroid-responsive elements in the alpha-cardiac myosin heavy chain gene promoter. AB - The role of two putative, cis-acting thyroid hormone-responsive elements, TRE1 and TRE2, located at -129 to -149 and -102 to -120, respectively, on the murine alpha-myosin heavy chain (MHC) gene, has been investigated in transgenic mice. These motifs are present in a 4.5-kilobase fragment lying upstream of the transcriptional start site of the mouse alpha-MHC gene: this fragment directs appropriate expression of a reporter gene in transgenic mice (Subramaniam, A., Jones, W. K., Gulick, J., Wert, S., Neumann, J., and Robbins, J. (1991) J. Biol. Chem. 266, 24613-24620). Here, we independently mutate the TRE1 and TRE2 elements by base substitution. The mice were analyzed for transgene expression in different muscle and non-muscle tissues including the atria and ventricles. Normal levels of transgene expression were observed in euthyroid mice carrying a mutation in TRE1. In contrast to these results, mice in which TRE2 was mutated showed reduced levels of CAT activity in both the atria and ventricles, suggesting a previously undefined role for this element in the constitutive up regulation of the alpha-MHC gene. In hypothyroid mice carrying either of these mutations, the complete cessation of ventricular expression of the chloramphenicol acetyltransferase transcripts that takes place in the alpha-5.5 (wild type) animals did not occur. PMID- 8440719 TI - Helicase-deficient cysteine to glycine substitution mutants of Escherichia coli replication protein PriA retain single-stranded DNA-dependent ATPase activity. Zn2+ stimulation of mutant PriA helicase and primosome assembly activities. AB - The PriA replication protein of Escherichia coli guides the ordered assembly of the primosome, the mobile, multiprotein, bidirectional, DNA replication priming/helicase complex of which it is an integral part. Although the PriA protein is not essential for viability, primosome assembly via a PriA-dependent pathway is required for normal cellular replication and growth. The PriA protein itself is multifunctional. In addition to its role in directing primosome assembly, PriA is a site-specific, single-stranded DNA-dependent ATPase (dATPase) and a 3'-->5' DNA translocase and helicase. In an attempt to assess how each individual PriA activity is related to the others (i.e. can one activity function independently of the others or are they intrinsically coupled?), a series of site directed mutations within priA have been created. priA encodes a cysteine-rich motif, the sequence of which suggests that this region of the protein may be involved in metal binding. Biochemical characterization of three purified cysteine to glycine substitution mutant PriA proteins revealed that these mutant proteins retained their site-specific single-stranded DNA-dependent ATPase activity. However, two of the three mutant proteins were completely incapable of any helicase activity. Residual helicase activity of the third mutant PriA protein could be stimulated 3-fold by the presence of low concentrations of Zn2+ ions. Primosomes assembled with the mutant PriA proteins were also defective in both their ability to act as bidirectional helicase complexes, as well as their ability to synthesize primers for extension by the DNA polymerase III holoenzyme. The results presented here suggest that the cysteine-rich region of PriA is indeed involved in metal binding and that single cysteine to glycine substitutions within this region result in the uncoupling of the ATPase activity of PriA from both its helicase activity and its ability to interact correctly with the DNA template and the six other primosomal proteins. PMID- 8440720 TI - Gene structure and expression of an unusual protein kinase from Plasmodium falciparum homologous at its carboxyl terminus with the EF hand calcium-binding proteins. AB - An unusual protein kinase gene, termed PfCPK, was isolated from Plasmodium falciparum. The gene, which contains five exons and four introns, encodes a product with a predicted length of 524 amino acids. The amino-terminal segment of the predicted protein contains all of the conserved sequences characteristic of a protein kinase catalytic domain and has a high homology to several protein serine threonine kinase subfamilies (30-41% amino acid identities). These subfamilies include calcium/calmodulin-dependent protein kinases, calcium-dependent protein kinase, ribosomal S6 protein kinase, cyclic nucleotide-dependent protein kinases, protein kinase C, and the yeast SNF1 subfamily. All of these protein kinases are relatively close in the phylogeny tree and within the kinase catalytic domains have about 35% amino acid identities to each other, suggesting that PfCPK is also in this region of the phylogeny tree. An unusual feature of PfCPK is that its carboxyl-terminal segment displays homology to the EF hand calcium-binding proteins, for example 34% amino acid identity to chicken fast skeletal muscle troponin C and 35% amino acid identity to human calmodulin. Like troponin Cs and calmodulins, PfCPK also contains four EF hand calcium-binding motifs. Furthermore, the four introns in the PfCPK gene are all located in the carboxyl terminal putative EF hand calcium-binding region (EF hand calcium-binding proteins from higher eukaryotes generally contain multiple introns). This combination of a protein kinase and an EF hand calcium-binding protein in a single polypeptide implies that PfCPK may be directly activated by calcium. Constructs containing the full-length PfCPK cDNA have been expressed in Escherichia coli at a high level to generate a 60-kDa recombinant protein. Compared with similar fractions from control cells, the fraction containing PfCPK recombinant protein exhibited an elevated protein kinase activity which was Ca(2+)-dependent. PMID- 8440721 TI - Tryptophan super-repressors with alanine 77 changes. AB - The binding of L-tryptophan to Escherichia coli tryptophan aporepressor enables the holorepressor complex to bind operator DNA tightly. The side chain of residue alanine 77 is located in one of the most flexible regions of Trp repressor, between residues critical for binding DNA. Codon-directed mutagenesis was used to make genes encoding mutant Trp repressors with each of the 19 naturally occurring amino acid changes of Ala77. The 19 mutant proteins are made at the same steady state levels as wild type. Sensitive challenge phage assays show that 7 of the 19 mutant proteins (Cys, Ser, Val, Leu, Thr, Ile, and Lys) are more active than wild type protein when tryptophan is limiting in vivo. Among these 7 mutant super aporepressors, proteins with Cys and Ser changes also are super-holorepressors, because they repress better than wild-type holorepressor when tryptophan is in excess. These results and others suggest that super-aporepressors associate more poorly than wild-type aporepressor with nonspecific DNA. Consistent with this idea, these 7 changes are predicted to disrupt the tertiary structure of aporepressor, but have more limited effects on the structure of holorepressor. PMID- 8440722 TI - 3-Hydroxy-3-methylglutaryl coenzyme A lyase (HL). Cloning of human and chicken liver HL cDNAs and characterization of a mutation causing human HL deficiency. AB - 3-Hydroxy-3-methylglutaryl coenzyme A lyase (HL) catalyzes the final step of ketogenesis, an important pathway of mammalian energy metabolism. HL deficiency is an autosomal recessive inborn error in man leading to episodes of hypoglycemia and coma. Using the N-terminal peptide sequence of purified chicken liver HL, we designed degenerate sequence primers and amplified an 89-base pair (bp) chicken liver HL cDNA fragment. Longer cDNA clones for chicken (1384 bp) and human (1575 bp) HL were obtained by library screening. The peptide sequence predicted from the chicken clone contains two peptides from purified chicken HL. Mature human and chicken HL are 298-residue peptides. The sequence of the human clone predicts a 27-residue mitochondrial leader and a 31.6-kDa mature HL peptide. Human fibroblast and liver RNA contain a single 1.7-kilobase HL message. Two Acadian French-Canadian siblings with HL deficiency were homozygous for a 2-base pair deletion within the Ser-69 codon (S69fs(-2)), predicted to result in a truncated nonfunctional HL peptide lacking a complete active site. S69fs(-2) was not present in 12 other HL-deficient patients of 10 other ethnic origins, showing that HL deficiency is genetically heterogeneous. PMID- 8440724 TI - Chimeric regulatory light chains as probes of smooth muscle myosin function. AB - Functional domains of the smooth muscle regulatory light chain (LC) were identified from the assembly and motor properties of smooth muscle myosin containing chimeric LCs, in which the N- and C-terminal halves of the smooth and skeletal LCs were interchanged. A C-terminal domain was also expressed. The affinity of these LCs for the smooth muscle myosin heavy chain (HC) is: wild-type LC > N-skeletal/C-smooth > N-smooth/C-skeletal approximately skeletal LC >> C terminal domain. The C-terminal half of the LC thus contains an isoform-specific HC binding site, but the two halves of the LC must interact for tight binding. Smooth muscle myosin containing chimeric or skeletal LCs can no longer assume the folded monomeric conformation, suggesting that control of assembly involves both halves of the LC. Dephosphorylation/phosphorylation of the N-skeletal/C-smooth chimera nonetheless regulates the ability of smooth muscle myosin to move actin. Myosin containing phosphorylated N-smooth/C-skeletal or skeletal LCs, in contrast, is locked in the "off" state. Interactions between the stronger binding C-terminal domain of the LC and the HC are therefore primarily responsible for the regulatory capabilities of this subunit. Localization of the regulatory LC at the head/rod junction by electron microscopy establishes that phosphorylation induced changes must be transmitted over 10 nm within the head for product release to be enhanced. PMID- 8440723 TI - Evidence that a 550,000-dalton cartilage matrix glycoprotein is a chondrocyte membrane-associated protein closely related to ceruloplasmin. AB - Cartilage matrix glycoprotein (CMGP) is a disulfide-bonded 550,000-dalton protein that is synthesized by chondrocytes and ciliary epithelial cells. We have purified the protein from bovine and porcine articular cartilage and have sequenced two peptides, which both have significant homology with human ceruloplasmin, a copper-binding oxidase. Immunolocation analysis indicates that a commercial polyclonal antiserum to human ceruloplasmin reacts with bovine cartilage CMGP. Chelating columns made with copper bind CMGP from bovine cartilage extracts. CMGP is present in bovine chondrocyte membrane preparations purified from sucrose density gradients. Oligonucleotide probes have been synthesized based on the published sequence of the 3'-untranslated region and a portion of the C terminus of human ceruloplasmin and have been used to amplify a cDNA fragment from bovine cartilage and human liver libraries. CMGP demonstrates oxidase activity towards p-phenylenediamine similar to that of ceruloplasmin. These studies suggest that CMGP is closely related to, if not identical with, ceruloplasmin. It is possible that CMGP may be involved in metal transport into and/or within the chondrocyte. PMID- 8440725 TI - Crystallographic refinement of lignin peroxidase at 2 A. AB - The crystal structure of the major lignin peroxidase isozyme from Phanerocheate chrysosporium has been refined to an R = 0.15 for data between 8 A and 2.03 A. The refined model consists of 2 lignin peroxidase molecules in the asymmetric unit, 2 calcium ions per monomer, 1 glucosamine per monomer N-linked to Asn-257, and 476 water molecules per asymmetric unit. The model exhibits excellent geometry with a root mean square deviation from ideality in bond distances and angles of 0.014 A and 2.9 degrees, respectively. Molecule 1 consists of all 343 residues, while molecule 2 consists of residues 1-341. The overall root mean square deviation in backbone atoms between the 2 molecules in the asymmetric unit is 0.36 A. The refinement at 2.0 A confirms our conclusions based on the partially refined 2.6-A structure (Edwards, S. L., Raag, R., Wariishi, H., Gold, M. H., and Poulos, T. L. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 750-754). The overall fold of lignin peroxidase closely resembles that of cytochrome c peroxidase. A superimposition of alpha-carbons gives a root mean square deviation of 2.65 A between the two peroxidases and 1.66 A for the helices. The active sites also are similar since both contain a proximal histidine heme ligand hydrogen-bonded to a buried aspartate residue and both contain histidine and arginine residues in the distal peroxide binding pocket. The most obvious difference in the active site is that whereas cytochrome c peroxidase has tryptophan residues located in the proximal and distal heme pockets, lignin peroxidase has phenylalanines. There are four other especially noteworthy differences in the two structures. First, although the heme in cytochrome c peroxidase is recessed about 10 A from the molecular surface, the heme pocket is open to solvent. The analogous opening in lignin peroxidase is smaller which can explain in part the differences in reactivity of the two hemes. This same opening may provide the site for binding small aromatic substrates. Second, lignin peroxidase has a carboxylate-carboxylate hydrogen bond important for heme binding that is not present in cytochrome c peroxidase. Third, lignin peroxidase contains 2 structural calcium ions while cytochrome c peroxidase contains no calcium. The calciums in lignin peroxidase coordinate to residues near the C-terminal ends of the distal and proximal helices and hence are probably important for maintaining the integrity of the active site. Fourth, the extra 49 residues in lignin peroxidase not present in cytochrome c peroxidase constitutes the C-terminal end of the molecule with the C terminus situated at the "front" end of the molecule between the two heme propionates. PMID- 8440726 TI - Promoter and regulatory regions of the rat luteinizing hormone receptor gene. AB - The region of transcriptional activity in the rat luteinizing hormone receptor gene was localized to the 5'-flanking 173-base pair (bp) sequence in transfected mouse Leydig tumor cells and non-expressing Chinese hamster ovarian (CHO) and HeLa cells. Repression of activity in all cell types was induced by at least two domains located between -174 and -990 bp. An additional inhibitory region between -1237 and -2056 bp observed only in CHO and HeLa cells may contribute to the absence of receptor expression in these cells. Analysis of the 173-bp region revealed a promoter domain between -1 and -137 bp containing no TATA or CAAT boxes, but with three SP1 sites and three initiator elements located at transcriptional start sites -14, -19, and -33. Gel retardation studies showed a protein-binding DNA domain about 30 bp upstream of the transcriptional start sites and an adjacent domain containing an SP1 element that are required for maximal activity in all cell types and may play a role in basal transcription. A second promoter domain (-120 to -173 bp) with a protein-binding SP1 element had minor activity in Leydig cells but was prominent in CHO and HeLa cells. Leydig cell-specific DNA-binding protein(s) for each of the promoter domains were detected and may be of importance in transcriptional regulation. The control of gene transcription by differential activation of these promoter domains could be involved in hormone-induced regulation of luteinizing hormone receptor expression in the gonads. PMID- 8440727 TI - Engineering of cytochrome P450 2B1 specificity. Conversion of an androgen 16 beta hydroxylase to a 15 alpha-hydroxylase. AB - Six site-directed mutants of cytochrome P450 2B1 were constructed, and function was evaluated in COS cell microsomes by monitoring testosterone and androstenedione hydroxylation and inactivation by chloramphenicol. Mutants Ile 114-->Val and Ile-114-->Ala exhibited marked decreases in androgen 16 beta-OH:16 alpha-OH ratios and increases in 15 alpha-OH:16-OH ratios. Since substitution of Gly-478 with Ala or Ser reduces 16 beta-hydroxylation in favor of 15 alpha hydroxylation, four double mutants containing Val or Ala at position 114 and Ala or Ser at position 478 were examined. For any given residue at position 114 (Ile, Val, or Ala), the 15 alpha-OH:16-OH ratio increased as residue 478 was changed from Gly to Ala to Ser, and for any residue at position 478, this ratio increased as residue 114 was changed from Ile to Val to Ala. As a consequence, the Ile-114- >Ala, Gly-478-->Ser mutant displayed an approximately 1000-fold higher androgen 15 alpha-OH:16-OH ratio compared with the parental enzyme and functionally resembles mouse P450 2A4 much more closely than P450 2B1. All three mutants with Val at position 114 retained susceptibility to inactivation by chloramphenicol, whereas inactivation was suppressed by Ala at this position. The results suggest the feasibility of an empirical approach to P450 engineering involving the appropriate combination of residues at a few critical sites to confer new regio- and stereoselectivity with retention of overall monooxygenase activity. PMID- 8440729 TI - PDGF-AB requires PDGF receptor alpha-subunits for high-affinity, but not for low affinity, binding and signal transduction. AB - There are two PDGF receptor proteins (PDGFR alpha and PDGFR beta) which are proposed to function as subunits to form a high-affinity dimeric PDGF receptor. One aspect of this model about which there is still disagreement is whether PDGF AB can bind to cells that express only PDGFR beta and, if so, whether PDGF-AB can act as an agonist or an antagonist. To address this question, we derived 3T3 cell lines from Patch mutant mouse embryos in which the PDGFR alpha gene is deleted but which express normal levels of PDGFR beta. Comparison between the binding and response properties of mutant and wild type 3T3 cell lines allowed us to define the contribution that PDGFR alpha makes to the ability of a cell to bind, and respond to, PDGF-AB. We found that PDGF-AB binds to PDGFR alpha-negative 3T3 cells and can induce DNA synthesis, PDGFR beta dimerization, and phosphorylation on tyrosine. In addition we found that PDGF-AB binding and stimulation of these activities is strongly temperature-dependent, whereas PDGF-AB binding and activation of PDGFR beta in the presence of PDGFR alpha is not. However, 3T3 cells that do not express PDGFR alpha require for activation PDGF-AB concentrations that were nearly 100-fold greater than for cells that do express PDGFR alpha. These results suggest that neither PDGF-AA nor PDGF-AB are likely to be physiologically significant activators of cells unless the cells express PDGFR alpha. PMID- 8440728 TI - Differing signal transductions elicited by three isoforms of platelet-derived growth factor in vascular smooth muscle cells. AB - The differing signal transductions elicited by three isoforms of platelet-derived growth factor (PDGF) were studied in cultured rat vascular smooth muscle cells (VSMC), which show different mitogenic responses to the three PDGF isoforms. PDGF BB elicited a variety of cellular signals, including the phosphorylation on tyrosine of phospholipase C-gamma 1 (PLC-gamma 1) and the PDGF receptor, formation of inositol 1,4,5-trisphosphate and diacylglycerol, degradation of phosphoinositides (phosphatidylinositol, phosphatidylinositol 4-phosphate, and phosphatidylinositol 4,5-bisphosphate) and elevation of intracellular calcium ([Ca2+]i). However, PDGF-AB failed to show some of these signals, although it stimulated [3H]thymidine incorporation to almost the same extent as PDGF-BB. Importantly, phosphorylation on tyrosine of the PLC-gamma 1 was far less (< 6.25%) in the case of PDGF-AB than that of PDGF-BB when assessed by immunoblotting. On the other hand, calcium ion entry from the extracellular medium was comparable in PDGF-AB- and PDGF-BB- stimulated VSMC. PDGF-AA, which did not stimulate [3H]thymidine incorporation, failed to show any of these effects with the exception of diacylglycerol formation. These observations suggest that the three PDGF isoforms stimulate different signal transduction pathways and that calcium ion entry, but not tyrosine phosphorylation of PLC gamma 1, is essential for PDGF-induced mitogenesis in VSMC. PMID- 8440730 TI - Recombinant Chinese hamster ovary cell matrix metalloprotease-3 (MMP-3, stromelysin-1). Role of calcium in promatrix metalloprotease-3 (pro-MMP-3, prostromelysin-1) activation and thermostability of the low mass catalytic domain of MMP-3. AB - Recombinant human fibroblast pro-MMP-3 (prostromelysin-1) expressed in Chinese hamster ovary cells and the zymogen from cultured human dermal fibroblasts have been purified by monoclonal antibody immunoaffinity chromatography, and the role of Ca2+ in proenzyme activation and thermostability of the low mass catalytic domain of MMP-3 has been investigated. In the presence of high Ca2+ (5.0 mM), the organomercurial aminophenylmercuric acetate (APMA) initiated the stepwise removal of both NH2- and COOH-terminal domains from both recombinant and dermal fibroblast proenzymes, resulting in the generation of a heterogeneous family of nonglycosylated low mass truncated active enzyme species beginning at Phe83. However, in the presence of low Ca2+ (0.1 mM), incubation of recombinant pro-MMP 3 with or without APMA did not result in formation of either the high or low mass forms of active MMP-3 but resulted in complete autolysis of both enzyme species. The concentration of Ca2+ required for optimal pro-MMP-3 activation and stability of the low mass catalytic domain was 2.0 mM. The low mass truncated enzyme species containing the catalytic domain were remarkably heat-stable (90 min at 60 degrees C) in high Ca2+ (5.0 mM) but rapidly autolyzed when heated at 60 degrees C in low Ca2+ (0.1 mM). The thermostability properties of MMP-3 appeared to be specific for Ca2+, since no other divalent metal ions tested were able to confer thermostability to the low mass catalytic domain of MMP-3. From homology to the thermostable bacterial metalloprotease, thermolysin, two putative Ca2+ binding sites were found in the catalytic domain of MMP-3 and several other members of the MMP gene family. These putative Ca2+ binding sites are postulated to play an important role in stabilizing active MMP-3 and other members of the matrix metalloprotease gene family by protecting them against autolysis. PMID- 8440731 TI - Multiple components of the T cell antigen receptor complex become tyrosine phosphorylated upon activation. AB - Triggering of the multicomponent T cell antigen receptor (TCR) complex results in several biochemical processes which are critical for the functional activation of T lymphocytes. One common process is the tyrosine phosphorylation of several proteins, including the TCR zeta chain. Here we show that in addition to TCR zeta, other subunits (CD3 gamma, CD3 delta, and CD3 epsilon) of the TCR complex can also be tyrosine-phosphorylated in response to antigen receptor stimulation. This rapid phosphorylation was detected in several mature murine T cell subsets, including CD4+ type 1 and 2 helper cells (TH1 and TH2). Therefore, tyrosine phosphorylation of multiple TCR components in addition to TCR zeta may be an important event during the initiation of the signaling cascade leading to T cell activation. PMID- 8440732 TI - Construction of Zn2+/Cd2+ hypersensitive cyanobacterial mutants lacking a functional metallothionein locus. AB - Eukaryotic metallothioneins (MTs) have been extensively studied, but the precise functions of most of these molecules are not yet fully understood. Prokaryotes are often more tractable for the analysis of gene function and we report here the generation of mutants of Synechococcus PCC 7942 (strain R2-PIM8) deficient in the MT locus, smt. Viability of these mutants, designated R2-PIM8 (smt), reveals that prokaryotic MT performs no "vital" role (such as donation of metals to metallo proteins) in Synechococcus. R2-PIM8 (smt) has reduced (approximately 5-fold) tolerance to elevated Zn2+, with detectable hypersensitivity to Cd2+. Restoration of Zn2+ tolerance was used as a selectable marker to isolate recombinants derived from R2-PIM8(smt) after reintroduction of a linear DNA fragment containing an uninterrupted smt locus. These smt-complemented cells also exhibited restored Cd2+ tolerance. Hypersensitivity to Cu2+ was not detected in R2-PIM8(smt) indicating independence of Cu2+ resistance from smt mediated metal (Zn2+/Cd2+) tolerance. PMID- 8440733 TI - Lysine 106 of the putative catalytic ATP-binding site of the Bacillus subtilis SecA protein is required for functional complementation of Escherichia coli secA mutants in vivo. AB - The SecA protein is a major component of the cellular machinery that mediates the translocation of proteins across the Escherichia coli plasma membrane. The secA gene from Bacillus subtilis was cloned and expressed in E. coli under the control of the lac or trc promoter. The temperature-sensitive growth and secretion defects of various E. coli secA mutants were complemented by the B. subtilis SecA protein, provided the protein was expressed at moderate levels. Under overproduction conditions, no complementation was observed. One of the main features of the SecA protein is the translocation ATPase activity which, together with the protonmotive force, drives the movement of proteins across the plasma membrane. A putative ATP-binding motif can be identified in the SecA protein resembling the consensus Walker A type motif. Replacement of a lysine residue at position 106, which corresponds to an invariable amino acid residue, in the consensus motif by asparagine (K106N) resulted in the loss of the ability of the B. subtilis SecA protein to complement the growth and secretion defects of E. coli secA mutants. In addition, the presence of the K106N SecA protein interfered with protein translocation, most likely at an ATP-requiring step. We conclude that lysine 106 is part of the catalytic ATP-binding site of the B. subtilis SecA protein, which is required for protein translocation in vivo. PMID- 8440734 TI - Properties of the medium chain/long chain carnitine acyltransferase purified from rat liver microsomes. AB - Carnitine octanoyltransferase (COT) purified from rat liver microsomes has K0.5 values between 1.0 and 4.0 microM for saturated 6-carbon to 16-carbon length acyl CoAs, with little differences in Vmax values. The reaction rate is linear with time in the forward direction (acyl-CoA-->acylcarnitine), but it increases with time when assayed in the reverse direction (acylcarnitine-->acyl-CoA). The K0.5 for decanoylcarnitine and CoASH are 0.3 mM for CoASH and between 1.0 and 4.0 mM for decanoylcarnitine. The kinetic data indicate that the enzyme functions in the direction of acyl-carnitine formation. It is moderately inhibited by aminocarnitine, and D-carnitine and etomoxiryl-CoA are weak inhibitors; malonyl CoA does not inhibit the enzyme. The enzyme has little, if any, capacity to use valproylcarnitine, 3-methylglutarylcarnitine, or pivaloylcarnitine as a substrate. Polyclonal antibodies prepared against COT give a positive Western blot against the purified enzyme and against a protein in microsomes having the molecular mass of COT (53 kDA). Antimitochondrial CPT and antiperoxisomal CAT did not show appreciable cross-reactivity with purified microsomal COT. The inhibitor data, the kinetic data, the molecular masses, and the Western blotting profiles all show that the enzyme purified from rat liver microsomes is a different carnitine acyltransferase than those previously purified from other organelles. PMID- 8440735 TI - Identification of 40 S ribosomal protein S6 phosphorylation sites in Swiss mouse 3T3 fibroblasts stimulated with serum. AB - All of the phosphorylation sites in 40 S ribosomal protein S6 derived from serum stimulated Swiss mouse 3T3 cells are found within a small cyanogen bromide (CNBr) peptide derived from the carboxyl terminus, Lys218-Lys249. Further cleavage of the CNBr peptide or the intact protein with endoproteinase Lys-C (endo Lys-C) generated a single phosphorylated peptide, implying that all the sites of phosphorylation resided either between Arg231 and Lys243 or between Arg231 and Lys249 if cleavage at Lys243 was blocked by phosphorylation at a nearby residue. To discern between these possibilities and to identify the phosphorylation sites, the protein was purified from serum-stimulated cells and cleaved with endo Lys-C, and the single endo Lys-C phosphorylated peptide was isolated and sequenced following conversion of all the phosphorylated serines to S-ethylcysteine. The results show that the phosphorylated peptide extends from Arg231 to Lys249 and that the sites of phosphorylation in vivo are Ser235, Ser240, Ser244, and Ser247. PMID- 8440736 TI - Squid glutathione S-transferase. Relationships with other glutathione S transferases and S-crystallins of cephalopods. AB - Glutathione S-transferase (GST, EC 2.5.1.18) was purified from the digestive gland of the squid Ommastrephes sloani pacificus. It had high enzymatic activity for the 1-chloro-2,4-dinitrobenzene substrate and was composed of a major and a minor polypeptide band, both with molecular masses near 25 kDa on SDS polyacrylamide gels. GST cDNA clones were derived from the digestive gland mRNA. The deduced GSTs of the longest cDNAs (pGST5 and pGST11) containing the entire coding sequence have a molecular mass near 23 kDa. Sequence comparisons showed that the squid GST is 42-44% identical to both squid and octopus S-crystallins (the major proteins of the lens), 32-34% identical to class pi and 29-32% identical to class alpha GSTs of vertebrates, and 19-23% identical to other GSTs of vertebrates and insects. Northern blot hybridization revealed that GST mRNAs were much more abundant in the digestive gland than in the testis, mantle, or lens. Analysis of a squid GST gene indicated that it has an exon-intron structure similar to that of the vertebrate class pi GST gene. An apparently novel repetitive element was identified in the 5'-flanking sequence of the squid GST gene. Our results suggest that multiple duplications of an ancestral GST gene gave rise to a family of enzymatically inactive crystallins specialized for lens refraction and one (or two) active GST enzyme expressed preferentially, but not exclusively, in the digestive gland in squids. This differs from the innovation of refractive function from a metabolic enzyme by increased expression in the lens with minimal or no gene duplication, as occurred among the enzyme crystallins of vertebrates. PMID- 8440737 TI - Aristolochene synthase. Isolation, characterization, and bacterial expression of a sesquiterpenoid biosynthetic gene (Ari1) from Penicillium roqueforti. AB - Aristolochene is the likely precursor of the sesquiterpenoid toxins produced by a number of filamentous fungi. One of these, PR-toxin, is produced by Penicillium roqueforti. We report here the isolation of a gene (Ari1) coding for the sesquiterpene cyclase, aristolochene synthase (AS), from P. roqueforti. Nucleotide sequence analysis of genomic and cDNA clones revealed that the Ari1 gene contains two introns. A Protein A/AS fusion enzyme was expressed in Escherichia coli and shown to have sesquiterpene cyclase activity. Analysis of the Protein A/AS fusion enzyme reaction mixtures by TLC and gas chromatography/mass spectrometry identified aristolochene as a major product. The Ari1 gene encodes a polypeptide of molecular weight 39,200. Expression of Ari1 occurs in stationary phase cultures of P. roqueforti and appears to be transcriptionally regulated. PMID- 8440738 TI - Yeast AMP deaminase. Catalytic activity in Schizosaccharomyces pombe and chromosomal location in Saccharomyces cerevisiae. AB - The AMP deaminase gene was mapped to chromosome XIII of Saccharomyces cerevisiae strain JM1901. The AMP deaminase gene is located near SUP5, GAL80, SUF7, and SUF22. The presence of AMP deaminase in the fission yeast Schizosaccharomyces pombe was examined by comparing DNA hybridization, protein immunoreactivity, and catalytic activity from S. cerevisiae, known to contain the protein, to S. pombe. DNA hybridization experiments using the cloned S. cerevisiae AMP deaminase gene failed to hybridize to the genomic DNA from S. pombe strain 972h-s. Protein extracts from S. pombe and S. cerevisiae were analyzed in parallel and exhibited comparable AMP deaminase activities. Analysis of reaction intermediates in cell extracts of S. pombe established that IMP is formed directly from AMP without intervening steps. The AMP deaminase of S. pombe was purified 1,100-fold to a specific catalytic activity of 67 mumol/min/mg of protein. Purified protein interacted weakly with polyclonal antibodies prepared against S. cerevisiae AMP deaminase. AMP deaminases from both S. cerevisiae and S. pombe were activated by ATP with micromolar activation constants, are inhibited by coformycin, and are specific for AMP when compared to other purine nucleosides and nucleotides. The results establish that S. pombe contains an AMP deaminase with catalytic properties similar to that from S. cerevisiae, even though the DNA sequences of the genes and the immunoreactivity of the protein from S. pombe differs considerably from the AMP deaminase of S. cerevisiae. Genetic analysis of the pathways of purine metabolism in S. pombe (Pourquie, J., and Heslot, H. (1971) Genet. Res. 18, 33-44) had indicated the absence of AMP deaminase. The presence of a regulated AMP deaminase in S. pombe supports the hypothesis that eukaryotes regulate adenine nucleotide pools by the activity of AMP deaminase. PMID- 8440739 TI - Characterization of a lipophilic antifolate resistance provoked by treatment of mammalian cells with the antiparasitic agent pyrimethamine. AB - We describe the characterization of an antitumor drug resistance following multiple step selection of hamster cells to the 2,4-diaminopyrimidines (DAP) metoprine, pyrimethamine (Pyr), and trimethoprim (Tmp). Pyr and Tmp are DAP lipophilic antifolates currently used as antiparasitic and antibacterial antibiotics, respectively. Dihydrofolate reductase (DHFR) from hamster cells bore a low or poor affinity to these DAP as compared to the hydrophilic folate antagonist methotrexate (MTX). Metoprine-resistant cells over-expressed DHFR enzyme and consequently displayed a high level of resistance to both hydrophilic and lipophilic antifolates including DAP but maintained wild type sensitivity to pleiotropic drugs involved in multi-drug resistance (MDR). In contrast, although Pyr- and Tmp-resistant cells expressed parental levels of wild type DHFR, they displayed a high degree of resistance to DAP and, surprisingly, to the lipophilic MTX analogs piritrexim (PTX) and trimetrexate (TMTX), while maintaining sensitivity to MTX. These drug-resistant cells maintained wild type mRNA levels of the MDR gene product P-glycoprotein and showed collateral hypersensitivity to pleiotropic drugs. To study the underlying mechanism of this apparently new resistance phenotype, we have employed fluorescein-methotrexate (F-MTX) labeling of cells and its displacement by different antifolates. Parental AA8 and Pyr resistant cells showed a similar level of F-MTX labeling, however, while DAP, TMTX, and PTX showed an efficient competitive displacement of F-MTX from AA8 cells, Pyr-resistant cells displayed a persistent retention of F-MTX labeling in the presence of high concentrations of these lipophilic antifolates. Pyr resistant cells showed a wild type displacement of F-MTX with MTX. This DAP resistance phenotype was unstable as it was rapidly lost upon growth under nonselective conditions. Furthermore, when the antifolate resistance levels of Pyr-resistant cells were plotted versus the ratios of the 50% F-MTX displacement values obtained with resistant and parental AA8 cells, a good correlation (r2 > 0.98) was obtained. We conclude that Pyr-resistant cells possess a novel phenotype that derives its resistance to lipophilic antifolates solely from a predominant decrease in the accumulation of DAP and lipid-soluble analogs of MTX. PMID- 8440740 TI - Selective sympathectomy of the liver: a comparison of orthotopic liver transplantation and intraportal 6-hydroxydopamine injection. AB - 1. Tissue noradrenaline (NA) levels correlate well with the extent of sympathetic innervation of that tissue. 2. In this study the distribution of NA throughout the different lobes of the rat liver was studied. The extent of sympathectomy by means of either orthotopic liver transplantation (OLT) (n = 7) or chemical denervation by intraportal administration of 6-hydroxydopamine (6-OH-DA) (n = 8) was examined. 3. In the normally innervated rat liver, NA was homogeneously distributed throughout the organ. Tissue NA was decreased both by OLT (> 99%) and 6-OH-DA (93%) (both P < 0.001 versus control). 4. Samples of the renal cortex and left ventricle were taken as reference tissues. OLT did not result in any change in reference tissue NA, however, 6-OH-DA decreased renal cortex NA by 93% and ventricular NA by 76%, respectively (both P < 0.01 versus OLT). 5. We conclude that OLT causes selective and complete hepatic sympathectomy but that 6-OH-DA causes incomplete denervation of the liver and significant denervation of other organs. PMID- 8440741 TI - Utilization of interleukin-2 gene transfer in local immunotherapy of cancer. AB - It has been previously found that local administration of Balb/c plasmacytoma cells transformed and made non-tumorigenic by insertion of the cloned murine interleukin-2 (IL-2) gene induced regressions of a variety of murine tumours including the original Balb/c plasmacytoma X63-Ag8.653 growing in syngeneic mice. The tumour-inhibitory effect of the plasmacytoma cells transformed by IL-2 cDNA and designated as X63-m-IL-2 was due to their high constitutive production of IL 2. Here we show that admixture of syngeneic spleen cells to the X63-m-IL-2 transformants substantially (P < 0.025) increased the antitumour efficacy of the transformants. Balb/c spleen cells co-cultivated with X63-m-IL-2 cells in vitro yielded predominantly Thy 1.2+, CD3+, LFA-1+ lymphocytes, cytolytic for the X63 Ag8.653 plasmacytoma as well as for other murine tumours, including the X63-m-IL 2 target cells. PMID- 8440742 TI - Cost: the new factor clinical cancer investigators must learn to consider. PMID- 8440744 TI - Generalised giant-cell tumour of bone: successful treatment of pulmonary metastases with interferon alpha, a case report. AB - We report on a 37-year-old female patient with generalised giant-cell tumour of the bone, whose tumour was refractory to conventional chemotherapy. Subsequent treatment with interferon alpha 2a in increasing dosage from 4 x 10(6) IU (three times a week) to 9 x 10(6) IU (three times a week) led to a significant decrease of pulmonary metastases and a stabilisation of the disease after 12 months of treatment. In progressive chemotherapy refractory giant-cell tumour interferon alpha 2a may be of therapeutic benefit. PMID- 8440743 TI - Molecular mechanism of stomach carcinogenesis. AB - Gene changes in multiple oncogenes, multiple growth factors and multiple tumor suppressor genes are observed in stomach cancer. Among them, those most commonly implicated in both well-differentiated adenocarcinoma and poorly differentiated adenocarcinoma are inactivation (mutations and allele loss) of the p53 gene, and activation (abnormal expression and amplification) of the c-met gene. Moreover, they occur at an early stage of stomach carcinogenesis. In addition, loss of heterozygosity (LOH) on chromosome 5q (APC locus) is frequently associated with well-differentiated adenocarcinoma. LOH on chromosome 18q (DCC locus) and LOH of the bcl-2 gene also are common events of well-differentiated adenocarcinoma. LOH on chromosomes 1q and 7q may be involved in the progression of well differentiated adenocarcinoma. Conversely, the development of poorly differentiated adenocarcinoma, in addition to changes in p53 and c-met genes, requires reduction or dysfunction of cadherin. Overexpression of bcl-2 protein is observed in poorly differentiated adenocarcinoma or signet-ring cell carcinoma. Moreover, the K-sam gene is amplified preferentially in poorly differentiated adenocarcinoma of scirrhous carcinoma. K-sam amplification in scirrhous carcinoma often occurs independently of c-met gene amplification. LOH on chromosome 1p also is relatively common in poorly differentiated adenocarcinoma. Exceptionally, signet-ring cell carcinoma shares APC mutations. There are some differences in expression of the growth-factor/receptor system between well-differentiated adenocarcinoma and poorly differentiated adenocarcinoma. Moreover, interaction between cell-adhesion molecules in tumor cells expressing c-met and hepatocyte growth factor (HGF) from stromal cells is linked with morphogenesis of two histological types of stomach cancer. Intestinal metaplasia and adenoma of the stomach also contain p53 mutations and K-ras mutations or tpr-met rearrangement. Taken together, different genetic pathways of stomach carcinogenesis may exist for poorly differentiated and well-differentiated stomach cancers. Some of the latter may develop by a cumulative series of gene alterations similar to those of colorectal cancer. PMID- 8440745 TI - International Society for Biomedical Research on Alcoholism: relationship of cell necrosis and proliferation, free radicals and other agents to alcohol-related cancers. PMID- 8440746 TI - Multiple mechanisms for regulation of steroid hormone action. PMID- 8440747 TI - Estrogen receptor mutations in breast cancer. AB - It is fairly well accepted that the presence of estrogen receptor (ER) identifies those breast cancer patients with a lower risk of relapse and better overall survival [Clark and McGuire, 1988], and the measurement of ER has become a standard assay in the clinical management of breast cancer. Receptor status also provides a guideline for those tumors which may be responsive to hormonal intervention [McGuire 1978; Osborne et al., 1980; Rose et al., 1985]. But only about half of ER-positive patients will respond to the various hormonal therapies available, and of those who do initially respond, most will eventually develop hormonally unresponsive disease following a period of treatment even though ER is often still present. Loss of ER from initially ER-positive tumors biopsied again at a later date has been estimated at only 19% [Gross et al., 1984]. Obviously the simple measurement of ER presence by ligand-binding assays does not provide us with an adequate estimate of the functional state of the receptor. In 1985 Sluyser and Mester hypothesized that the loss of hormone dependence of certain breast tumors may be due to the presence of mutated or truncated steroid receptors that activate transcription even in the absence of hormone [Sluyser and Mester, 1985]. Based on the recent identification of several ER sequence variants in human breast cancer cell lines and tumor specimens, we would now like to propose that some of these identified mutations play a role in receptor dysfunction in vivo, and will review those ER mutations which may prove to be important in breast cancer progression. PMID- 8440748 TI - On the mechanism of DNA binding by nuclear hormone receptors: a structural and functional perspective. AB - The nuclear hormone receptor DNA-binding domain consists of two zinc finger-like modules whose amino acids are highly conserved among the members of the receptor superfamily. In this review, we describe the various genetic, biochemical, and structural experiments that have been carried out primarily for the DNA-binding domains of the glucocorticoid and estrogen receptors. We describe how the structural and functional information have permitted us to predict properties of the DNA-binding domains of other nuclear receptors. We postulate how receptors discriminate closely related response elements through sequence-specific contacts and distinguish symmetry of target sites through protein-protein interactions. This mechanism explains in part how the receptors regulate diverse sets of genes from a limited repertoire of core response elements. Lastly, we describe the stereochemical basis of nuclear receptor dysfunction in certain clinical disorders. PMID- 8440749 TI - Mechanisms of transcriptional activation by steroid hormone receptors. AB - Steroid hormones are involved in cell growth, development, and differentiation. The hormonal signal is mediated by nuclear receptors which represent a specific class of transcription factors. During the last few years, the cloning of all the major steroid hormone receptors increased our insight into how the hormonal signal converts the receptor into a transcriptional activator. Good progress has been made towards understanding the mechanism of steroid hormone action. In this review we will discuss the role of heat shock proteins in the process of transcriptional activation, the mechanistic differences between the hormone (agonist) and the antihormone (antagonist), the resulting functional consequences, and a possible mode by which transcriptional activation is mediated. PMID- 8440750 TI - 4-Quinolones cause a selective loss of mitochondrial DNA from mouse L1210 leukemia cells. AB - The 4-quinolone antibiotics nalidixic acid and ciprofloxacin are potent inhibitors of the bacterial type II topoisomerase DNA gyrase. Treatment of mouse L1210 leukemia cells with these drugs resulted in a delayed inhibition of cell proliferation. Prior to inhibition of cell proliferation, there was a time dependent decrease in the cellular content of mitochondrial DNA (mtDNA). The decrease in mtDNA was associated with a decrease in the rate of mitochondrial respiration and an increase in the concentration of lactate in the growth medium. Inhibition of cell proliferation by 4-quinolones was reversible upon drug washout. However, there was a 2- to 4-day lag before the growth rate returned to normal levels. This was preceded by an increase in mtDNA content and mitochondrial respiration. These studies suggest that inhibition of mammalian cell proliferation by 4-quinolone drugs is related to the selective depletion of mtDNA. PMID- 8440751 TI - Expression of histone and alkaline phosphatase genes in UMR 106-01 rat osteoblast like cells exposed to the Hoechst dye H33342. AB - The fluorescent Dye H33342 (H342) is a bis-benzimidazole used for intravital fluorescent staining. In this report, we found that H342 completely abolished histone 2a mRNA but had no effect on alkaline phosphatase gene expression and protein synthesis in UMR 106-01 rat osteoblast-like cells. The complete loss of histone 2a mRNA occurred after only 20 min of treatment with H342. This effect is unlikely to be a result of inhibition of DNA synthesis, which was only partly suppressed. The mechanism of the action of H342 on histone 2a mRNA is presently unknown. PMID- 8440752 TI - Effect of retinyl acetate on the assembly of the fibronectin extracellular matrix and the processing of the fibronectin receptor beta subunit of confluent C3H/10T1/2 mouse embryo fibroblasts. AB - The mouse embryo fibroblast cell line, C3H/10T1/2, synthesized and deposited a large amount of fibronectin especially in the pericellular matrix. Confluent cultures of these cells cultured in the presence of 0.3 micrograms/ml of retinyl acetate released cell surface fibronectin and the extracellular matrix fibronectin fibrils were disorganized. The immunoblot analysis demonstrated that the number of the fibronectin receptor was decreased in the prolonged culturing of retinyl acetate-treated cells. Immunoprecipitation of 35S-methionine pulse chase labeled cell extracts by antifibronectin receptor antibody indicated that about one-half of the pre-beta subunit was processed and converted to the mature form in control cells, and only about one-fourth of the pre-beta subunit was processed in the retinyl acetate-treated confluent cells. 1-deoxymannojirimycin (MNJ), which is an inhibitor of oligosaccharide processing, induced disorganization of the extracellular matrix fibronectin assembly similar to that observed with retinyl acetate. The results of this study suggest that a mechanism of action of retinyl acetate is inhibition of the glycosylation during processing of the fibronectin receptor, a step necessary for fibronectin binding and for assembly of the extracellular matrix. PMID- 8440753 TI - Temporally different poly(adenosine diphosphate-ribosylation) signals are required for DNA replication and cell division in early embryos of sea urchins. AB - To analyze the temporal relationship of poly(adenosine diphosphate [ADP] ribosylation) signal with DNA replication and cell divisions, the effect of 3 aminobenzamide (3ABA), an inhibitor of the poly(ADP-ribose)synthetase, was determined in vivo during the first cleavage division of sea urchins. The incorporation of 3H-thymidine into DNA was monitored and cleavage division was examined by light microscopy. The poly(ADP-ribose) neosynthesized on CS histone variants was measured by labeling with 3H-adenosine during the two initial embryonic cell cycles and the inhibitory effect of 3ABA on this poly(ADP ribosylation) was determined. The results obtained indicate that the CS histone variants are poly(ADP-ribosylated) de novo during the initial cell cycles of embryonic development. The synthesis of poly(ADP-ribose) is decreased but not abolished by 20 mM of 3ABA. The incubation of zygotes in 3ABA at the entrance into S1 phase decreased 3H-thymidine incorporation into DNA in phase S2, while S1 was unaltered. Alternatively, when the same treatment was applied to zygotes at the exit of S1 phase, a block of the first cleavage division and a retardation of S2 phase were observed. The inhibitory effect of 3ABA on both DNA replication and cell division was totally reversible by a release of the zygotes from this inhibition. Taking together these observations it may be concluded that the poly(ADP-ribosylation) signals related to embryonic DNA replication are not contemporaneous with S phase progression but are a requirement before its initiation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8440754 TI - Detection and characterization of low abundance cellular proteins that specifically increase upon loss of the metastatic phenotype. AB - Human epidermoid carcinoma (HEp-3) cells are highly tumorigenic and metastatic in vivo, but their metastatic phenotype is progressively and uniquely lost upon serial passage in vitro. The nonmetastatic phenotype is fully reversible to the highly metastatic state when HEp-3 cells are passaged back in vivo. To study the complex process of metastasis and its possible negative regulation by specific gene products, the expression of specific proteins between the highly metastatic and nonmetastatic HEp-3 cells was investigated by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and subsequent computer assisted analyses. Concomitant with the in vitro loss of metastatic potential of HEp-3 cells is the elevated expression of a subset of low abundance proteins detectable in 2D-PAGE but not apparent in high resolution one dimensional PAGE. When the HEp-3 cells revert to the metastatic state, the expression of these proteins declines. The increased cellular abundance of four distinct proteins directly correlates with the loss of the metastatic phenotype: two of the four proteins are associated with isolated cellular membranes (36kD, pI 5.7; 22kDa, pI 5.6), one protein fractionates with the cytoplasm (65kD, pI 6.2), and one protein is enriched in the nuclei fraction (32kD, pI 5.8). These data indicate that computer-assisted analysis of highly sensitive, large-format, 2D-PAGE can be used to identify specific proteins in subcellular compartments that are candidates for negative regulators of the metastatic process. PMID- 8440755 TI - New method for rapid characterization of molecular shapes: applications in drug design. AB - We present a method for the rapid quantitative shape match between two molecules or a molecule and a template, using atom triplets as descriptors. This technique can be used either as a rapid screen preceding the computationally expensive shape-based docking method developed by Kuntz and co-workers or as a stand-alone method to rank compounds in a large database for their fit to a shape template. The merits and limitations of this method are discussed in detail with examples. PMID- 8440756 TI - Computers in the new drug application process. AB - Before a company can introduce a new pharmaceutical in the United States, it must receive approval of a New Drug Application (NDA) from the Food and Drug Administration. As a document that may consist of over 100,000 pages, the NDA presents the company's evidence that the new pharmaceutical is safe and effective for treating a particular medical condition. This paper describes four major issues in the NDA process: the role of computers in the FDA review, standards for compound documents and data, substitution of computer-assisted new drug applications (CANDAs) and electronic versions of other documents for paper versions, and management of the heterogeneous collection of material on which an NDA is based. PMID- 8440757 TI - Drug development and registration in Japan: threshold of transition. AB - The responsibility for the regulation of pharmaceuticals is situated within the Pharmaceutical Affairs Bureau (PAB) of the Japanese Ministry of Health and Welfare. The scientific evaluation of the application is undertaken by a series of committees consisting of independent senior members of the medical and scientific community whereas all communication between them and the pharmaceutical company is conducted through PAB offices (Koseisho). As in the U.S., the Japanese drug application covers product quality, safety, and efficacy, but the actual data requirements differ between the two countries. Some of these differences have a basis in Japanese regulations whereas others emulate from demands set by senior members of the medical fraternity who carry great sway in Japan. These cause concern to international pharmaceutical companies since they may require studies to be duplicated with consequent delays. Moves toward the achievement of global harmonization of regulatory requirements with the associated benefits of reducing the numbers of animals sacrificed in the total development program and of important new medications reaching patients earlier are discussed. PMID- 8440758 TI - The effect of naproxen and interleukin-1 on proteoglycan catabolism and on neutral metalloproteinase activity in normal articular cartilage in vitro. AB - The events in inflammatory and degenerative joint diseases involve major changes in the metabolic events in the articular cartilage. The effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on articular cartilage metabolism remain unclear, however. The objective of this catabolism of proteoglycans in articular cartilage explants maintained in culture. Release of proteoglycan from the cartilage was compared with release of neutral metalloproteinase activity. The effect of the drug also was determined on the IL-1-stimulated release of proteoglycan and neutral metalloproteinase activity from the explants. At concentrations that included those present in synovial fluids of patients treated with the drug, naproxen sodium was found to suppress the release of proteoglycan and neutral metalloproteinase activity from the articular cartilage extracts. This is in contrast to the well-documented effect of interleukin-1 (IL-1), which was shown to stimulate release of proteoglycan and neutral metalloproteinase activity from articular cartilage. The effect of naproxen sodium on the IL-1 stimulated release was to suppress, but not totally overcome, the increased release of proteoglycan and neutral metalloproteinase activity. In summary, these in vitro studies of cartilage metabolism indicate that naproxen sodium has the potential to suppress catabolic activities in articular cartilage, including those that are motivated by IL-1. PMID- 8440759 TI - Receptor-based pharmacokinetic-pharmacodynamic analysis of corticosteroids. AB - The pharmacodynamics of three corticosteroids were investigated after intravenous administration of the phosphate esters of methylprednisolone, dexamethasone, and triamcinolone acetonide to healthy subjects at 20, 50, and 80 mg as well as placebo. Twenty-two different pharmacodynamic parameters were followed as a function of time for 48 hours. Statistically significant effects of the glucocorticoids were an increase in blood glucose levels, a decrease in the number of lymphocytes, eosinophils, basophils, and monocytes, and an increase in the number of granulocytes and stab cells. For the most significant pharmacodynamic effects (lymphocytes, granulocytes, and glucose) a previously derived integrated pharmacokinetic/pharmacodynamic model using plasma concentrations, protein-binding data, and in vitro receptor-binding affinities was used to predict the pharmacodynamic effect-time profiles. Good agreement of predicted and measured effects was observed, confirming the validity of the model. The clinical significance of the model was demonstrated by comparison of model-predicted maintenance doses with empirically determined clinical equivalency doses. PMID- 8440760 TI - Effect of unbound clearance on binding parameters of valproic acid to serum proteins. AB - Nine healthy subjects received 400 mg sodium valproate orally in the fasting state. Binding parameters of valproic acid to serum proteins were determined by Scatchard analysis for individual series of valproic acid data. Total and unbound (intrinsic) clearances (CLt and CLu) were calculated by dividing the dose by the appropriate area under the serum drug concentration-time curve. Unbound clearance correlated positively with the product of association constant (Ka) and concentration of free protein ((P)) (P < .05). Conversely, no significant correlation was found between CLt and binding parameters. The average unbound concentration correlated negatively with both CLu and ka(P) values. The result indicates an effect of CLu on Ka(P) value of valproic acid. PMID- 8440761 TI - Effect of ethanol on metabolic responses to treadmill running in well-trained men. AB - The metabolic effects of ethanol on treadmill performance were determined in four trained runners. Ethanol in doses of 25 mL in 150 mL of grapefruit juice (total volume) or grapefruit juice was randomly administered 10 minutes before and at 30 minutes of a 60-minute treadmill run. The speed and grade of the treadmill was adjusted to elicit an average oxygen consumption (VO2) of 80 to 85% of the subjects' VO2max. Three of the four subjects could not complete the treadmill run after the administration of ethanol. Administration of ethanol resulted in significant increases in the heart rate responses to treadmill running above those for the placebo grapefruit treatment. VO2 was higher after ethanol administration than the placebo grapefruit juice treatment, but these values were not significant. Blood glucose content rose significantly between 0 and 30 minutes of treadmill running for both the ethanol and placebo grapefruit juice treatments. Between 30 minutes of treadmill running and the termination of the exercise, the blood glucose level decreased significantly by 24% after the second ethanol treatment at 30 minutes of exercise. Plasma fatty acid, triglyceride, creatine phosphokinase, and renin contents followed expected exercise changes. It was concluded that the administration of ethanol adversely influenced treadmill exercise performance by eliciting a hypoglycemic effect between 30 minutes and the termination of the exercise. PMID- 8440762 TI - Pharmacokinetics of oral nifedipine in different populations. AB - Nifedipine disposition varies among populations. Reports on oral nifedipine pharmacokinetics show that peak plasma levels and AUC values are higher in Mexican and Japanese than in European and North American subjects. Increased nifedipine bioavailability in the nonwhite populations is likely due to nutritional habits. Certain flavonoids that inhibit the first-pass metabolism of dihydropyridines are present in the diets of both Mexican and Japanese. Differences in phenotypes may play a role in interethnic variability. PMID- 8440763 TI - Digoxin pharmacokinetics and perindopril in heart failure patients. AB - The influence of chronic perindopril treatment on digoxin pharmacokinetics was investigated in 10 patients with mild chronic heart failure under stable diuretic and digitalis treatment and normal renal function. Digoxin was administered at a dose of 0.125 mg/day (n = 2) or 0.250 mg/day (n = 8). The 24-hour steady-state digoxin profile was assessed before and after concomitant administration of perindopril for 1 month at doses of 2 mg once a day for the first 8 days and 4 mg once a day for the remaining 21 days. Chronic treatment with perindopril produced no significant effect on mean (+/- standard deviation) digoxin serum area under the curve for 24 hours (17.9 +/- 7.4 versus 16.3 +/- 4.4 ng/mL.h), peak digoxin concentration (1.3 +/- 0.54 versus 1.2 +/- 0.36 ng/mL), time to peak concentration (3 versus 4 hours), and apparent oral clearance of digoxin (237.7 +/- 109.6 versus 237.4 +/- 79.5 mL/min). Clinical and biologic tolerance of perindopril was good throughout the study. Chronic administration of perindopril did not alter steady-state digoxin kinetics in patients with mild chronic heart failure and normal renal function, indicating that no adaptation of the digoxin dose is required during co-prescription with perindopril in such patients. PMID- 8440764 TI - Continuous intravenous dosing with ciprostene using a portable pump in ambulatory patients. AB - Parenteral compounds present special drug delivery challenges. This open-label study evaluated a portable infusion pump as a means to deliver intravenous ciprostene, a stable prostacyclin analog. Ten patients with peripheral vascular disease and claudication received ciprostene (titrated to 120 ng/kg/min) infused over 8 hours 1 day per week for 4 consecutive weeks. Patients successfully maintained the pump strapped to the waist. The mean +/- standard deviation delivery error, with volumes of 6 to 10 mL over 8 hours, was -0.895 +/- 3.177%. Accordingly, the pump performed well with a potent drug under these clinical conditions. Headache, flushing, and infusion site irritation during infusion were the most frequent side effects. Blood pressure remained unchanged during infusion; however, heart rate increased significantly (P < .05, maximum increase was 13.9 +/- 2.1 beats per minute [mean +/- standard error of the mean]. Mean (+/ standard error of the mean) relative claudication times on treadmill remained unchanged; however, absolute claudication times increased (P < .05) from 6.6 +/- 1.8 to 10.0 +/- 2.2 minutes. Ciprostene inhibited adenosine diphosphate-induced platelet aggregation by 56.0 +/- 12.7% (mean +/- standard error of the mean). Mean template bleeding times and plasma concentrations of platelet-specific proteins (beta-thromboglobulin, platelet factor 4) did not change. PMID- 8440765 TI - Pharmacokinetics of beta-methyldigoxin in subjects with normal and impaired renal function. AB - Beta-methyldigoxin (beta-MD) was administered orally (0.2 mg) to 24 patients with various degrees of renal function, to investigate its pharmacokinetic characteristics related to renal function. Serum and urine collected until 120 hours after dosing were assayed for beta-MD and digoxin by high-performance liquid chromatography and fluorescence polarization immunoassay method. The steady-state volume of distribution decreased proportionately as creatinine clearance (CLCR) decreased, although steady-state volume of distribution of hemodialysis patients had large interindividual variability, and their mean value was not different from that of patients with normal renal function. Both renal clearance of beta-MD and digoxin were significantly correlated with CLCR (r = .820, P < .001 and r = .822, P < .01, respectively), and the slope of regression line for beta-MD was only 44% that for digoxin. Significantly reduced urinary excretion of total drug (beta-MD plus digoxin) was shown in patients with CLCR below 50 mL/minute/1.48 m2. This study suggests that the dosage modification is not necessary until CLCR decreases to below 50 mL/minute/1.48 m2, but careful attention should be given in the use of beta-MD in patients with CLCR below this value. PMID- 8440766 TI - Steady-state pharmacokinetics and dose relationship of nicotine delivered from Nicoderm (Nicotine Transdermal System). AB - An open-label, randomized, crossover study determined nicotine pharmacokinetics at steady state of a new Nicotine Transdermal System in 24 healthy adult male smokers. Three doses were each administered for 5 days: 7, 14 and 21 mg nicotine per day. Plasma nicotine concentrations reached steady state by the third day and were sustained throughout the 24-hour application periods. Mean steady-state nicotine and cotinine area under the curve (AUC0-24), maximum plasma concentration (Cmax), minimum plasma concentration (Cmin), average plasma concentration (Cavg), and total urinary cotinine were proportional to the dose of nicotine released in vitro from Nicotine Transdermal System. Time to reach peak concentration (tmax), half-life (t1/2), relative degree of fluctuation (DF) in steady-state plasma nicotine and cotinine concentrations, and renal cotinine clearance were similar for all three dosages, indicating linear pharmacokinetics and no change in nicotine metabolism with increasing dose. Findings from a second study also reflect the linear dose relationship for this Nicotine Transdermal System within the 7 to 21 mg/day dosage range. Bioequivalence based on the confidence interval test was demonstrated for a single application of Nicotine Transdermal System 21 mg/day and the same total dosage achieved by combined administration of Nicotine Transdermal System 7 mg/day plus Nicotine Transdermal System 14 mg/day, although there were small statistical differences. This Nicotine Transdermal System has a well-defined pharmacokinetic profile, with sustained plasma nicotine concentrations, and nicotine pharmacokinetics that are independent of the dose of this Nicotine Transdermal System. PMID- 8440768 TI - Evaluation of the pharmacokinetics and tolerability of tirilazad mesylate, a 21 aminosteroid free radical scavenger: II. Multiple-dose administration. AB - The multiple dose tolerability and pharmacokinetics of tirilazad mesylate, a 21 aminosteroid free radical scavenger, were assessed in 50 healthy male volunteers. Volunteers were randomized to receive intravenous normal saline placebo (n = 10), citrate vehicle placebo (n = 10), or 0.5 mg/kg/day (n = 6), 1.0 mg/kg/day (n = 6), 2.0 mg/kg/day (n = 6), 4.0 mg/kg/day (n = 6), or 6.0 mg/kg/day (n = 6) tirilazad mesylate in divided doses every 6 hours for 5 days, for a total of 21 doses. Drug was infused over 10 or 30 minutes. All tirilazad mesylate treatment groups and the citrate vehicle group had significantly more frequent and more intense pain at the injection site than did the saline group, but the pain intensity did not require interruption of dosing. Three episodes of clinical thrombophlebitis were observed. No statistically significant effects of tirilazad mesylate on blood pressure, heart rate, electrocardiograms, or renal function were apparent. Moderate and transient increases in serum alanine transaminase were observed in several subjects. In the 6.0 mg/kg/day group, 50% of the subjects exhibited increased alanine transaminase. Tirilazad mesylate did not significantly affect measures of glucocorticoid activity (blood glucose, adrenocorticotropic hormone, cortisol, eosinophil, or lymphocyte levels). Tirilazad mesylate pharmacokinetics were linear over the dosage range studied. Steady state appeared to be achieved by the fifth day of dosing. After the last dose, a mean terminal half-life of 35 hours was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8440767 TI - Single- and multiple-dose pharmacokinetics of Nicoderm (Nicotine Transdermal System). AB - The pharmacokinetics and tolerability of single and multiple applications of Nicotine Transdermal Systems (NTS), designed to deliver 14 mg of nicotine per 24 hours, were investigated in 20 healthy adult male smokers. After a single application, mean Cmax and tmax for plasma nicotine were 12.2 ng/mL and 4.4 hours, respectively. Plasma nicotine concentrations rose rapidly and then remained steady between 12 and 24 hours after application. The apparent nicotine half-life (t1/2) after system removal was 3.2 hours. Steady state was attained by the second day of multiple application, and mean steady-state nicotine Cavg was 25% higher on day 5 compared with the first NTS application. Steady-state plasma cotinine was reached by the fourth day of multiple application and, as with nicotine, Cavg and Cmax increased, tmax decreased, and t1/2 did not change compared with single application. The mean ratios of cotinine-to-nicotine area under the curve (AUC) values for single and multiple NTS applications were 14.0 and 15.8, respectively. The pharmacokinetics of nicotine and cotinine were linear between single and multiple NTS applications. The nicotine transdermal systems were generally well tolerated. PMID- 8440769 TI - Retinal transplants in congenitally blind mice: patterns of projection and synaptic connectivity. AB - Embryonic retinae were transplanted onto the midbrain of neonatal congenitally anophthalmic mice and neonatal mice from which both eyes had been removed. When donor mice of the AKR strain were used, the detailed patterns of the transplant projections to the host brain were demonstrated with an antibody to Thy-1.1, which specifically stains neural tissue derived from AKR donors. Many of the subcortical visual centers were innervated, and only small differences were encountered between anophthalmic and eye-enucleated mice. The terminal arbors of transplant-derived axons could not be classified as in normal animals, although several distinct arbor types were seen. In the superior colliculus, the laminar arrangements that characterize normal retinal arbors were disrupted. Despite this, the synaptic patterns formed by transplant-derived axons in the superior colliculus of anophthalmic mice compared very closely with those of retinal axons in normal, sighted animals. These observations indicate that the ability of a retinal transplant to innervate the host brain and to form the synaptic arrays characteristic of optic terminals are not dependent on prior innervation, nor do they appear to be influenced by the events that follow eye removal. PMID- 8440770 TI - Developmental study of the gene expression for alpha and gamma subunits of enolase in the rat brain by in situ hybridization histochemistry. AB - The gene expression for alpha and gamma subunits of enolase, a dimeric enzyme in the glycolytic pathway, was examined in the developing brain of rats by in situ hybridization. The expression for the gamma subunit of enolase was first detected in post-mitotic neurons settled in the mantle zone at E13, and it increased progressively until the adult stage. Expression signals for the alpha subunit were discerned in two discrete regions showing different developmental changes: the signals in the proliferative ventricular zone were intense at E13 and decreased and eventually disappeared around birth, whereas the signals in the mantle zone persisted until the adult stage. In the adult brain, mRNAs for the alpha and gamma subunits were expressed widely in neurons, resulting in almost similar temporal patterns in the brain except for the cerebellum. Expression levels of the alpha subunit in adult glial cells were below the detection threshold of the in situ hybridization analysis. These findings suggest that both alpha and gamma enolase subunits participate in energy production in neurons of the mature brain and that marked changes in the subunit composition of enolase occur according to both neuron type and maturation. PMID- 8440771 TI - NGF receptor (p75)-immunoreactivity in the developing primate basal ganglia. AB - The distribution of the p75 nerve growth factor receptor (NGFr) was determined within the developing human basal ganglia in specimens between weeks 16 through 40 of gestation, 5 years of age, and adulthood. Although NGFr-immunoreactive neurons were rarely seen in the caudate nucleus, a few such neurons were seen in the putamen between prenatal weeks 16 and 26 of development. At 26 and 40 weeks of gestation, the putamen also displayed NGFr-immunoreactive fibers of putative basal forebrain origin. Some of these fibers coursed through the putamen en route to the cortex while others appeared to remain within the putamen. The external segment of the globus pallidus contained dense collections of NGFr-immunoreactive neurons between 16 and 26 weeks of gestation, whereas the internal segment was devoid of immunoreactive perikarya. A few NGFr-immunoreactive neurons were observed within the globus pallidus at embryonic week 40. The expression of NGFr immunoreactive neurons within the external segment of the globus pallidus was paralleled by a dense granular NGFr-immunoreactive terminal-like staining pattern within the subthalamic nucleus. This staining pattern was most intense at midgestation (weeks 21-26) and was not observed at 40 weeks of gestation or in adulthood. Interestingly, a similar NGFr-immunoreactive terminal-like pattern was also observed within the monkey subthalamic nucleus at embryonic day 120. These data indicate that NGF receptor mediated mechanisms may underlie developmental processes within the primate basal ganglia. The absence of NGFr-immunoreactive neurons within the caudate nucleus, and the paucity of such neurons in the putamen, suggests that NGF receptors play a limited role in primate neostriatal development. Alternatively, developmental events mediated through NGF receptors may occur prior to embryonic week 16. Furthermore, an NGFr/trophic interaction appears to underlie the development of the pallidal-subthalamic nucleus pathway. PMID- 8440772 TI - Barrelettes--architectonic vibrissal representations in the brainstem trigeminal complex of the mouse. II. Normal post-natal development. AB - Vibrissal representations in the brainstem trigeminal complex (BTC) of rodents are manifested as architectural sub-units called barrelettes. The development of barrelettes was studied by using Nissl staining, cytochrome oxidase histochemistry, and Golgi-impregnation methods. On the day of birth (PND-1), barrelettes are manifested as longitudinal, histochemical cylinders in sub-nuclei principalis, interpolaris and caudalis of the BTC. One day later (PND-2), fully formed histochemical barrelette formations are seen in the three sub-nuclei. The development of cytoarchitectural barrelettes lags behind histochemical barrelettes by about two days. Between PND-2 and PND-3, longitudinal cytoarchitectonic cylinders begin to appear. By PND-3, BTC neurons segregate into five rows of barrelettes in the coronal plane. Segmentation of rows into individual barrelettes begins on PND-4, and complete cytoarchitectonic barrelette formations are seen by PND-5. Golgi-impregnation shows that on the day of birth, primary afferent terminals and dendritic arbors of second-order trigeminal neurons within the BTC are short and poorly ramified. Over the next five post natal days, lengthening of these processes as well as elaboration into secondary and tertiary branches take place. Growth of these processes continues for two additional weeks, contributing to the increase in barrelette neuropils (hollows). As the neuropils expand, neuronal somata are pushed toward barrelette sides. Morphometric measurements show that there is a relatively constant rate of growth of barrelettes over the first three post-natal weeks. The growth rate of the barrelette formations is identical to that of BTC as a whole. Thus, at the time of birth, the volume of neural tissue in the brainstem allotted to vibrissae is fixed relative to that allotted to other sensory receptors. Several features of the early development of barrelettes are identified: (1) Chemoarchitectural barrelettes appear before cytoarchitectural barrelettes, suggesting that terminal arbors of primary trigeminal afferents are organized before their target neurons form barrelettes. (2) Early cytoarchitecture is manifested in the form of unsegmented rows, suggesting that rough, row-based topological maps are first formed, which are then fine-tuned into individual sub-units. Recent evidence shows that other vibrissal representations--thalamic barreloids and cortical barrels--also follow these "afferent-before-target" and "row-before-individual units" sequences of development. This gradual, afferent-dependent fine-tuning of topological organization is analogous to similar events during the early development of the visual system, and may be a general feature of developing sensory systems.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8440773 TI - Network of GABAergic large basket cells in cat visual cortex (area 18): implication for lateral disinhibition. AB - Anatomical and immunohistochemical data indicate that, in addition to pyramidal neurons, nonpyramidal cells are exposed to perisomatic inhibition mediated by gamma-aminobutyric acid (GABA)-containing terminals. However, no direct information is available as yet for the origin of GABAergic inputs to morphologically identified GABAergic neurons. In the present paper, we studied the topographical and synaptic relationship between identified GABAergic large basket cells and their immunohistochemically characterized target neurons revealed by parvalbumin-(PV) and GABA immunostaining in the same material. Extracellularly applied biocytin labelled a total of 36 and 9 large basket cells in layers III and V, respectively. Of these, the axonal arborizations of two basket cells, BC1 and BC2, were reconstructed. The axon of BC1 occupied an area of about 2.3 x 2.2 mm2 in layer III, providing a total of 2,755 terminals. The axon of BC2 showed an overall extent of 3.8 x 1.7 mm2 in layer V elongated in the anteroposterior direction, and gave off 1,599 terminals. Immunostaining for PV was carried out to reveal putative nonpyramidal targets for BC1 and BC2. It was found that in addition to immunonegative cells, they established an average of 4 6 perisomatic contacts onto each of 58 (BC1) and 33 (BC2) PV-immunopositive neurons. For electron microscopic verification, 23 terminals apposing the somata of 12 PV-immunopositive neurons were selected. Each terminal was found to establish symmetrical (type II) contacts with its targeted cell. Furthermore, the distribution of soma area of the targeted PV-immunopositive cells and of identified large basket cells showed remarkable similarity, implying that the two populations were actually the same. In addition, the average horizontal distance between neighbouring PV-immunopositive target cells was found to be about 100 microns both in layers III and V. The results suggest that in area 18 the same large basket cell provides direct inhibition to certain pyramidal cells and facilitation to other pyramidal neurons, by inhibiting their presynaptic large basket cells at regular intervals. PMID- 8440774 TI - Effect of wound healing and tissue transplantation on the navigation of axons in organ-cultured embryonic chick eyes. AB - Wound closure and repair of embryonic neuroepithelium were studied in organ cultured embryonic retinae. Eyes from 3 to 4-day-old embryos were cultured after removing pieces of retinal tissue. During the subsequent 24 hours of incubation, the 150 to 200 microns wide holes in the retina closed completely. Histological studies showed that the wound closure was not accomplished by cell migration or cell proliferation, but by an approximation of the wound edges mediated by extracellular matrix fibrils of the vitreous body. The wound contraction facilitated the integration of transplants into the retinal neuroepithelium with a perfect alignment of the implants with the host at the vitreal surface. Within 24 hours, a continuous inner limiting membrane between transplant and host retina was established. The effect of wound healing and tissue transplantation on the navigation of optic axons in the retina was investigated. The wound contraction in the retina caused the optic axons near the lesion site to grow to the wound center, where the axons traversed the retina and formed a neuroma at the ventricular side, resembling the organization of axons at the optic disc. In the transplantation paradigm, axons from the host retina migrated into the transplant and vice versa. However, due to the wound contraction around the transplant, most axons grew into the interface between the transplant and host tissue. PMID- 8440775 TI - Ultrastructure of the extraocular photoreceptor in the genitalia of a butterfly, Papilio xuthus. AB - This paper describes the ultrastructure of a sensory neuron found in the extraocular photoreceptive site on the butterfly genitalia. Our previous studies have shown that there are two pairs of the photoreceptive sites in a butterfly (four per individual). Each photoreceptive site is recognizable by a transparent area in the pigmented cuticle of the genitalia. From the nerve that extends from the transparent cuticle to the last abdominal ganglion, a sustained train of single unit spikes can be recorded in response to a light flash. The single unit spikes disappear when the transparent cuticle is covered, thus indicating that a single photoreceptor exists close to it. Here, we examined complete serial semithin sections of plastic-embedded photoreceptive sites of both male and female, and observed an ovoid structure close to the transparent cuticle. The structure contained the cell body of a sensory neuron whose axon was in the nerve branch from which the photoresponse had been recorded. Further electron microscopy revealed that the cell body extended a few distal processes that protrude tubular membrane from the tip, forming a structure resembling the phaosome (from Greek; phaos = light, some = body) which was first described in the earthworm dermal photoreceptors. The sensory neuron was also found in a surgically isolated nerve-photoreceptor preparation that responded to the light. We therefore propose that the phaosome-containing sensory neuron is the butterfly genital photoreceptor. PMID- 8440776 TI - Jerzy Edwin Rose 1909-1992. PMID- 8440777 TI - Connections of somatosensory cortex in megachiropteran bats: the evolution of cortical fields in mammals. AB - The cortical connections of the primary somatosensory area (SI or 3b), a caudal somatosensory field (area 1/2), the second somatosensory area (SII), the parietal ventral area (PV), the ventral somatosensory area (VS), and the lateral parietal area (LP) were investigated in grey headed flying foxes by injecting anatomical tracers into electrophysiologically identified locations in these fields. The receptive fields for clusters of neurons were mapped with sufficient density for injection sites to be related to the boundaries of fields, and to representations of specific body parts within the fields. In all cases, cortex was flattened and sectioned parallel to the cortical surface. Sections were stained for myelin and architectonic features of cortex were related to physiological mapping and connection patterns. We found patterns of topographic and nontopographic connections between 3b and adjacent anterior parietal fields 3a and 1/2, and fields caudolateral to 3b (SII and PV). Area 1/2 had both topographic and nontopographic connections with 3b, PP, and SII. Connections of SII and PV with areas 3b, 3a, and 1/2 were roughly topographic, although there was clear evidence for nontopographic connections between these fields. SII was most densely connected with area 1/2, while PV was most densely connected with 3b. SII had additional connections with fields in lateral parietal cortex and with subdivisions of motor cortex. Other connections of PV were with subdivisions of motor cortex and pyriform cortex. Laminar differences in connection patterns of SII and PV with surrounding cortex were also observed. Injections in the ventral somatosensory area revealed connections with SII, PV, area 1/2, auditory cortex, entorhinal cortex, and pyriform cortex. Finally, the lateral parietal field had very dense connections with posterior parietal cortex, caudal temporal cortex, and with subdivisions of motor cortex. Our results indicate that the 3b region is not homogeneous, but is composed of myelin dense and light regions, associated with 3b proper and invaginations of area 1/2, respectively. Connections of myelin dense 3b were different from invaginating portions of myelin light area 1/2. Our findings that 3b is densely interconnected with PV and moderately to lightly interconnected with SII supports the notion that SII and PV have been confused across mammals and across studies. Our connectional evidence provides further support for our hypothesis that area 1/2 is partially incorporated in 3b and has led to theories of the evolution of cortical fields in mammals. PMID- 8440778 TI - Synapsin I gene expression in the adult rat brain with comparative analysis of mRNA and protein in the hippocampus. AB - Synapsin I is the best characterized member of a family of neuron-specific phosphoproteins thought to be involved in the regulation of neurotransmitter release. In this report, we present the first extensive in situ hybridization study detailing the regional and cellular distribution of synapsin I mRNA in the adult rat brain. Both the regional distribution and relative levels of synapsin I mRNA established by in situ hybridization were confirmed by RNA blot analysis. Our data demonstrate the widespread yet regionally variable expression of synapsin I mRNA throughout the adult rat brain. The greatest abundance of synapsin I mRNA was found in the pyramidal neurons of the CA3 and CA4 fields of the hippocampus, and in the mitral and internal granular cell layers of the olfactory bulb. Other areas abundant in synapsin I mRNA were the layer II neurons of the piriform cortex and layer II and V neurons of the entorhinal cortex, the granule cell neurons of the dentate gyrus, the pyramidal neurons of hippocampal fields CA1 and CA2, and the cells of the parasubiculum. In general, the pattern of expression of synapsin I mRNA paralleled those encoding other synaptic terminal-specific proteins, such as synaptophysin, VAMP-2, and SNAP-25, with noteworthy exceptions. To determine specifically how synapsin I mRNA levels are related to levels of synapsin I protein, we examined in detail the local distribution patterns of both synapsin I mRNA and protein in the rat hippocampus. These data revealed differential levels of expression of synapsin I mRNA and protein within defined synaptic circuits of the rat hippocampus. PMID- 8440779 TI - Localization of cannabinoid receptor mRNA in rat brain. AB - Cannabinoid receptor mRNA was localized in adult rat brain by 35S-tailed oligonucleotide probes and in situ hybridization histochemistry. Labelling is described as uniform or non-uniform depending on the relative intensities of individual cells expressing cannabinoid receptor mRNA within a given region or nucleus. Uniform labelling was found in the hypothalamus, thalamus, basal ganglia, cerebellum and brainstem. Non-uniform labelling that resulted from the presence of cells displaying two easily distinguishable intensities of hybridization signals was observed in several regions and nuclei in the forebrain (cerebral cortex, hippocampus, amygdala, certain olfactory structures). Olfactory associated structures, basal ganglia, hippocampus, and cerebellar cortex displayed the heaviest amounts of labelling. Many regions that displayed cannabinoid receptor mRNA could reasonably be identified as sources for cannabinoid receptors on the basis of well documented hodologic data. Other sites that were also clearly labelled could not be assigned as logical sources of cannabinoid receptors. The localization of cannabinoid receptor mRNA indicates that sensory, motor, cognitive, limbic, and autonomic systems should all be influenced by the activation of this receptor by either exogenous cannabimimetics, including marijuana, or the yet unknown endogenous "cannabinoid" ligand. PMID- 8440780 TI - Distribution of proneuropeptide Y-derived peptides in the brain of Rana esculenta and Xenopus laevis. AB - The distribution of proneuropeptide Y-containing perikarya and nerve fibers in the brain of Rana esculenta and Xenopus laevis was determined with antisera directed toward neuropeptide Y and the carboxyl terminal flanking peptide. The distribution of proneuropeptide Y-like immunoreactivity was similar in both anurans. In the telencephalon, immunoreactive perikarya were found in the olfactory bulb, all subdivisions of the pallium, the septum, pars lateralis of the amygdala, the nucleus accumbens, and the anterior preoptic area. In the diencephalon, labelled perikarya were detected in the ventromedial, ventrolateral and central thalamic nuclei, the magnocellular preoptic nucleus, the suprachiasmatic nucleus, the posterior tuberculum, and the infundibulum. Amacrine like cells were stained in the retina. In the pretectal area, posterior thalamic neurons showed intense, Golgi-like immunostaining. In the mesencephalon, immunoreactive cells were found in the reticular nucleus, the anteroventral tegmental nucleus, the optic tectum, the interpeduncular nucleus, and the torus semicircularis. In the rhombencephalon, labelled perikarya were detected in the secondary visceral nucleus, the central gray, the nucleus of the solitary tract, the dorsal column nuclei, and the spinal nucleus of the trigeminal nerve. Immunoreactive nerve fibers were observed in all areas of the brain that contained labelled perikarya. The densest accumulations were found in the accessory olfactory bulb, pars lateralis of the amygdala, the ventral habenula, the posterior pituitary, the optic tectum, the interpeduncular nucleus, and the saccular nucleus. The distribution of proneuropeptide Y-like immunoreactivity in the anuran brain showed many similarities to the distribution described for the amniote brain. PMID- 8440781 TI - Localization of cardiac vagal preganglionic motoneurones in the rat: immunocytochemical evidence of synaptic inputs containing 5-hydroxytryptamine. AB - The origin of cardiac vagal preganglionic motoneurones in the rat is still controversial and knowledge of the chemistry of synaptic inputs onto these neurones is limited. In this investigation vagal preganglionic motoneurones innervating the heart were identified by the retrograde transport of cholera toxin conjugated to horseradish peroxidase (CT-HRP) combined with the immunocytochemical localization of 5-hydroxytryptamine. Injection of CT-HRP into the myocardium resulted in the retrograde labelling of neurones primarily in the ventral regions of the nucleus ambiguus (75.1%). Labelled neurones were also distributed in a narrow band through the reticular formation extending between the dorsal motor nucleus of the vagus nerve and the nucleus ambiguus (17.3%) as well as in the dorsal motor nucleus itself (7.6%). A combination of retrograde labelling with immunocytochemistry for 5-hydroxytryptamine revealed that the neuronal perikarya and the dendrites of cardiac vagal motoneurones in the nucleus ambiguus were often ensheathed in 5-hydroxytryptamine-immunoreactive axonal boutons. Electron microscopic examination of this material confirmed that there were synaptic specializations between these boutons and the cardiac vagal motoneurones. The identification of 5-hydroxytryptamine-containing synaptic inputs to this population of vagal motoneurones provides further detail towards the understanding of the regulation of heart rate by the parasympathetic nervous system. PMID- 8440782 TI - Serotoninergic innervation of the dorsal column nuclei and its relation to cytoarchitectonic subdivisions: an immunohistochemical study in cats and monkeys (Aotus trivirgatus). AB - The serotoninergic innervation of the dorsal column nuclei (DCN) was investigated in cats and owl monkeys (Aotus trivirgatus) with immunohistochemical methods. A dense network of serotonin-immunoreactive fibers was present in the reticular regions of DCN in cats, and in the pars triangularis of the cuneate nucleus and the peripheral and caudal regions of the gracile nucleus in owl monkeys. The cat's cluster regions and the monkey's rotund regions were more sparsely innervated. Electron microscopic examination showed that the labeled fibers were thin and unmyelinated. Vesicle-containing, terminal-like structures were small. They were in contact with dendrites, other terminals and cell bodies, but synapses were rare. The results demonstrate that the serotoninergic projection to the DCN in both cats and owl monkeys is heterogeneously distributed in a pattern that is faithfully related to the cytoarchitectonic subdivisions of the DCN. The densely innervated reticular regions in the DCN of cats and the corresponding regions in monkeys are predominantly involved in the processing of sensory information to the cerebellum, either directly, or indirectly through projections to the inferior olive, pontine gray, tectum, pretectum, red nucleus, or zona incerta. Thus, the present findings suggest that the serotoninergic innervation of the DCN is primarily related to the DCN's involvement in motor functions. PMID- 8440783 TI - Noradrenergic innervation of the hypothalamus of rhesus monkeys: distribution of dopamine-beta-hydroxylase immunoreactive fibers and quantitative analysis of varicosities in the paraventricular nucleus. AB - The distribution of noradrenergic processes within the hypothalamus of rhesus monkeys (Macaca mulatta) was examined by immunohistochemistry with an antibody against dopamine-beta-hydroxylase. The results revealed that the pattern of dopamine-beta-hydroxylase immunoreactivity varied systematically throughout the rhesus monkey hypothalamus. Extremely high densities of dopamine-beta-hydroxylase immunoreactive processes were observed in the paraventricular and supraoptic nuclei, while relatively lower levels were found in the arcuate and dorsomedial nuclei and in the medial preoptic, perifornical, and suprachiasmatic areas. Moderate levels of dopamine-beta-hydroxylase immunoreactivity were found throughout the lateral hypothalamic area and in the internal lamina of the median eminence. Very few immunoreactive processes were found in the ventromedial nucleus or in the mammillary complex. Other midline diencephalic structures were found to have high densities of dopamine-beta-hydroxylase immunoreactivity, including the paraventricular nucleus of the thalamus and a discrete subregion of nucleus reuniens, the magnocellular subfascicular nucleus. A moderate density of dopamine-beta-hydroxylase immunoreactive processes were found in the rhomboid nucleus and zona incerta whereas little dopamine-beta-hydroxylase immunoreactivity was found in the fields of Forel, nucleus reuniens, or subthalamic nucleus. The differential distribution of dopamine-beta-hydroxylase immunoreactive processes may reflect a potential role of norepinephrine as a regulator of a variety of functions associated with the nuclei that are most heavily innervated, e.g., neuroendocrine release from the paraventricular and supraoptic nuclei, and gonadotropin release from the medial preoptic area and mediobasal hypothalamus. Additionally, quantitative analysis of dopamine-beta hydroxylase-immunoreactive varicosities was performed on a laser scanning microscope in both magnocellular and parvicellular regions of the paraventricular nucleus of the hypothalamus. The methodology employed in this study allowed for the high resolution of immunoreactive profiles through the volume of tissue being analyzed, and was more accurate than conventional light microscopy in terms of varicosity quantification. Quantitatively, a significant difference in the density of dopamine-beta-hydroxylase-immunoreactive varicosities was found between magnocellular and parvicellular regions, suggesting that parvicellular neurons received a denser noradrenergic input. These differential patterns may reflect an important functional role for norepinephrine in the regulation of anterior pituitary secretion through the hypothalamic-pituitary-adrenal stress axis. PMID- 8440784 TI - Fibronectin-like immunoreactivity of the basilar membrane of young and aged rats. AB - Dysfunction of cochlear mechanics has been hypothesized to be a source of age related hearing loss and the basilar membrane mass and stiffness contribute to normal cochlear mechanics. Fibronectin, a large, extracellular matrix protein and a major component of the basilar membrane, may contribute to both the mass and stiffness of the membrane. Mesothelial cells underlying the basilar membrane may produce the fibronectin and also contribute to the mass of the membrane. Changes in either the fibronectin or the mesothelial cells might, therefore, have an effect on cochlear mechanics. In order to assess basilar membrane changes in aged animals, young adult (2-4 months) and aged (24-26 months) Sprague-Dawley rats were evaluated for the presence of fibronectin-like protein and mesothelial cells. The basilar membrane in the young animals had strong fibronectin-like immunoreactivity throughout its length. The old animals, on the other hand, showed normal fibronectin immunoreactivity in the basilar membrane of the basal turn, but little or no reactivity in the apical cochlear turn. The number of mesothelial cells was reduced throughout the length of the membrane in aged animals, with the greatest loss in the basal turn (60% fewer cells). These two degenerative changes, which appear to be independent of each other, may contribute to the observed threshold shifts in aged cochleas. PMID- 8440785 TI - Visual system of a naturally microphthalmic mammal: the blind mole rat, Spalax ehrenbergi. AB - Retinal projections and visual thalamo-cortical connections were studied in the subterranean mole rat, belonging to the superspecies Spalax ehrenbergi, by anterograde and retrograde tracing techniques. Quantitative image analysis was used to estimate the relative density and distribution of retinal input to different primary visual nuclei. The visual system of Spalax presents a mosaic of both regressive and progressive morphological features. Following intraocular injections of horseradish peroxidase conjugates, the retina was found to project bilaterally to all visual structures described as receiving retinal afferents in non-fossorial rodents. Structures involved in form analysis and visually guided behaviors are reduced in size by more than 90%, receive a sparse retinal innervation, and are cytoarchitecturally poorly differentiated. The dorsal lateral geniculate nucleus, as defined by cyto- and myelo-architecture, cytochrome oxidase, and acetylcholinesterase distribution as well as by afferent and efferent connections, consists of a narrow sheet 3-5 neurons thick, in the dorsal thalamus. Connections with visual cortex are topographically organized but multiple cortical injections result in widespread and overlapping distributions of geniculate neurons, thus indicating that the cortical map of visual space is imprecise. The superficial layers of the superior colliculus are collapsed to a single layer, and the diffuse ipsilateral distribution of retinal afferents also suggests a lack of precise retinotopic relations. In the pretectum, both the olivary pretectal nucleus and the nucleus of the optic tract could be identified as receiving ipsilateral and contralateral retinal projections. The ventral lateral geniculate nucleus is also bilaterally innervated, but distinct subdivisions of this nucleus or the intergeniculate leaflet could not be distinguished. The retina sends a sparse projection to the dorsal and lateral terminal nuclei of the accessory optic system. The medial terminal nucleus is not present. In contrast to the above, structures of the "non-image forming" visual pathway involved in photoperiodic perception are well developed in Spalax. The suprachiasmatic nucleus receives a bilateral projection from the retina and the absolute size, cytoarchitecture, density, and distribution of retinal afferents in Spalax are comparable with those of other rodents. A relatively hypertrophied retinal projection is observed in the bed nucleus of the stria terminalis. Other regions which receive sparse visual input include the lateral and anterior hypothalamic areas, the retrochiasmatic region, the sub-paraventricular zone, the paraventricular hypothalamic nucleus, the anteroventral and anterodorsal nuclei, the lateral habenula, the mediodorsal nucleus, and the basal telencephalon.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8440786 TI - Cholinergic innervation of the human cerebellum. AB - Cholinergic innervation of the human cerebellum was investigated immunocytochemically by using a polyclonal rabbit antiserum against choline acetyltransferase. Immunoreactive structures were found throughout the cerebellar cortex but were localized predominantly in the vermis, flocculus, and tonsilla. These included 1) a population of Golgi cells in the granular layer; 2) a subpopulation of mossy fibers and glomerular rosettes; 3) thin, varicose fibers closely associated with the Purkinje cell layer and the molecular layer; and 4) a relatively dense network of fibers and terminals contributing to the glomerular formations in the granular layer. In the cerebellar nuclei, some cells stained positively for choline acetyltransferase, and a terminal field pattern could be detected with a distinct but sparse network of varicose fibers. Acetylcholine appears to be a primary transmitter in the vestibulocerebellar pathways at several levels, which may account for the potent effects of muscarinic antagonists in diminishing vestibular vertigo in humans. PMID- 8440787 TI - Multimorphic growth cones in the embryonic medicinal leech: relationship between shape changes and outgrowth transitions. AB - Comparative studies of growth cone morphology may provide insight into the mechanisms underlying motility and navigation in vivo. Here we analyzed the morphology of a unique set of growth cones in the embryonic medicinal leech, Hirudo medicinalis. The comb or C-cell is a transient cell found as a bilateral pair in each midbody segment. Early in development, from embryonic day (E)7 to E11, each C-cell adds and orients about 70 parallel growth cones that remain relatively nonmotile until E12 when rapid process outgrowth is initiated. Individual C-cells from E10 to E14 were injected with Lucifer yellow and growth cones were traced with a camera lucida. Growth cone morphology was quantified from the drawings. Lamellar regions increased in area with age and change in extension rate. Young, relatively nonmotile growth cones had numerous short filopodia in many orientations, while at highly motile stages filopodial number decreased, length increased, and orientation became more restricted in the direction of outgrowth. Thus, while filopodia were distributed symmetrically, such that the average filopodial angle was predictive of the direction of outgrowth at all stages, younger (relatively nonmotile) growth cones project more filopodia in many directions than do older more motile growth cones. These results suggest that: (1) alterations in morphology may reflect developmentally regulated changes in extension and the local environment, (2) these growth cones maintain a large area for environmental sampling as they increase extension rate, even as filopodia become more restricted in orientation, and (3) C-cell growth cones might progressively alter their affinity for local cellular cues as they initiate rapid and directed outgrowth. The C-cell of embryonic leech may provide a relatively simple system in which to test these ideas experimentally. PMID- 8440788 TI - Estimate of the total number of neurons and glial and endothelial cells in the rat spinal cord by means of the optical disector. AB - The total numbers of neurons and glial and endothelial cells in five rat spinal cords were estimated by stereological techniques. Each spinal cord was divided into 12 slabs of equal length. One transverse and one oblique slice was cut from each slab. The volumes of gray and white matter of each cord were then estimated by point-counting techniques on the transverse slices. By means of optical disectors and systematic sampling, the numerical densities of different cell types were estimated on 35 microns-thick plastic sections from the oblique slices. The total cell number was calculated by multiplying the numerical density by the total volume of gray and white matter. On average there were 15.1 and 21.1 million cells in white and gray matter, respectively. Of the cells in gray matter, 6.4 million were judged to be neurons, 4.3 million to be endothelial, and 10.3 million to be glial. Of the neurons, 1.7 million were located in the cervical region, 2.5 million in the thoracic, 1.6 million in the lumbar, and 0.6 million in the sacro-coccygeal region. The methods used are simple to perform, and the counting necessary to obtain a reliable estimate of cell number from one spinal cord can be carried out during the course of 1 day. The only major problem is reliable criteria for unambiguous cell classification. PMID- 8440789 TI - Immunocytochemical demonstration of early appearing astroglial structures that form boundaries and pathways along axon tracts in the fetal brain. AB - During normal development of the mammalian forebrain, the paired cerebral hemispheres are initially separated midsagittally by the connective tissue-filled longitudinal fissure. During subsequent stages, the hemispheres fuse as basal lamina is remodeled and fibroblasts are eliminated from the fissure to create new central nervous system (CNS) territory in the midline. Two axon pathways, the corpus callosum and dorsal callosal stria, eventually use this region as part of their pathway. In order to assess the possible role of glial cells in the fusion process and in the guidance of axons in this and several other areas of the forebrain, we have analyzed the developing brain in timed cat and mouse embryos with immunohistochemical and morphological techniques. With the use of astroglial specific antibodies and electron microscopy, we have visualized two distinct, primitive astroglial structures associated with the cerebral midline, and seven more associated with other specific brain regions. The way in which one of these structures moves as a column along the hemispheric midline in synchrony with seam formation suggests the possibility that during morphogenesis of the telencephalon, astrocytes may aid in the fusion process. In addition, the compact assemblage, early appearance and location of this and the other glial structures in relation to well defined neuroanatomical landmarks or axon pathways suggest that they may transiently compartmentalize relatively large regions of the CNS and organize certain developing fiber systems by acting as guides or barriers at critical stages of ontogeny. PMID- 8440790 TI - Cells of origin of the spinoparabrachial fibers in the rat: a study with fast blue and WGA-HRP. AB - The internal lateral (IL) subnucleus of the parabrachial nucleus (PB), which is one of the seven lateral subnuclei of the PB, receives information from the spinal cord. The IL subnucleus perhaps relays nociceptive signals to the intralaminar nuclei of the thalamus, apparently being implicated in the motivational-affective component of pain reaction. However, cells of origin of spinal fibers to the IL subnucleus have not been investigated sufficiently. We intended to clarify these cells by injection of fast blue or wheat germ agglutinin-conjugated horseradish peroxidase into the IL subnucleus and/or other lateral subnuclei in the rat. When the tracer was injected into the IL subnucleus, many cells were labeled bilaterally in laminae I, V, and VII, and in the dorsolateral and dorsomedial parts of the lateral funiculus throughout the entire length of the spinal cord. A small number of labeled cells appeared ipsilaterally in laminae II-IV and VI in the upper cervical segments and contralaterally in laminae VIII and X throughout the spinal cord. Labeled cells in lamina I were more numerous ipsilaterally than contralaterally in the first two cervical segments but were more numerous contralaterally than ipsilaterally in the remaining spinal segments. Labeled cells were seen with a contralateral predominance in lamina VII, but with an ipsilateral predominance in lamina V and in the dorsolateral and dorsomedial parts of the lateral funiculus. With tracer injected into the lateral subnuclei of the PB, excluding the IL subnucleus, labeled cells were found primarily in lamina I throughout the entire length of the spinal cord. These results show that cells giving rise to spinoparabrachial fibers were more numerous and more widely distributed than previously reported. PMID- 8440791 TI - The role of the right ventricle in determining cardiac output in the in the critically ill. PMID- 8440792 TI - Aspirin effect on early and late changes in acute lung injury in sheep. AB - OBJECTIVE: There have been several studies that have already explored the potential beneficial role of cyclo-oxygenase (CO) inhibitors on oleic acid (OA) induced lung injury in different species. These studies report no significant effect of CO inhibition, though thromboxane B2 (TxB2) was effectively blocked. However, recent studies indicate that pre-treatment with aspirin (ASA) preserve gas exchange in OA lung injury in dogs. Aim of our study has been to evaluate the potential beneficial effects of the pre-treatment with low doses of ASA on gas exchange, hemodynamics, respiratory mechanics, prostanoids and lung histology in OA-induced lung injury in sheep. DESIGN: 0.09 ml/kg of OA was administered into the right atrium of 14 anaesthetized sheep. Six received a bolus of ASA (10 mg/kg i.v.) 30 min before OA, the others saline as placebo. MEASUREMENTS AND RESULTS: Pulmonary and tissue gas exchange, pulmonary and systematic hemodynamics, respiratory system mechanics, TxB2 and 6-keto-PGF1 alpha, leukocytes and platelets concentrations were measured throughout the subsequent 3 h and lung histology was effected at end-experiment. The principal findings of our study are: 1) ASA reduces OA-induced early pulmonary vasoconstriction and bronchoconstriction, parallelled by a suppression of TxB2 generation; 2) the late increase in pulmonary artery pressure and airway resistance due to OA is not inhibited by ASA; 3) the early disturbance in pulmonary gas exchange is reduced by ASA, whereas the late severe deterioration is exaggerated by ASA; 4) the stability of tissue exchange ratio (R) at approximately 1 in ASA-group compared to its fall to approximately 0.7 in controls. CONCLUSION: Our findings suggest that ASA: 1) is only effective to treat the very transient TxB2-induced pulmonary vasoconstriction resulting in hydrostatic edema, and it is ineffective, even accentuates, the subsequent major pulmonary endothelial cell injury leading to alveolar flooding that is unrelated to TxB2; 2) has a transient protective effect on the TxB2-induced early bronchospasm; 3) has a biphasic behaviour on gas exchange, with a benefit which lasts only one hour and then results in a worse gas exchange; 4) has an immediate, stabilizing, persisting effect on R, contrasting with its transient effect on pulmonary hemodynamics and PaO2. PMID- 8440793 TI - Polymicrobial bacteremia in critically ill patients. AB - OBJECTIVE: To characterize the epidemiology of polymicrobial bacteremia (PMB) among critically ill patients. DESIGN: Prospective clinical study. SETTING: University medical center. PATIENTS: All patients with positive blood cultures in a medical-surgical ICU. MEASUREMENTS: PMB represents 8.4% of all true bacteremia in our ICU. Most of these patients were postoperative but none had malignancies or significant immunodepression. Over three-quarters of the episodes were nosocomial. No significant differences in factors associated with PMB were found when they were compared with a cohort of 154 monomicrobial episodes. Enterobacteriaceae were the most common organisms. Intravascular devices (42.8%) were the most common source of PMB, followed by intra-abdominal origin (21.4%). The overall mortality was 7.1%, a lower rate than has previously been described. CONCLUSIONS: We suggest catheter replacement in patients who develop PMB and improving techniques of catheter maintenance in order to reduce its incidence. PMID- 8440794 TI - Comparison of the hemodynamic effects of hydroxocobalamin and cobalt edetate at equipotent cyanide antidotal doses in conscious dogs. AB - OBJECTIVES: The hemodynamic effects of two cyanide antidotes, hydroxocobalamin and cobalt edetate were compared. DESIGN: This experimental study was performed in chronically instrumented conscious dogs and at equipotent cyanide antidotal doses (hydroxocobalamin 70 mg.kg-1; cobalt edetate 10.5 mg.kg-1). RESULTS: Peak plasma cobalt concentrations did not differ in the two groups (412 +/- 183 vs 400 +/- 160 mumol.l-1). Hydroxocobalamin induced a slight increase in mean arterial pressure (+17 +/- 9%, p < 0.05) and systemic resistance (+19 +/- 15%, p < 0.05). In contrast, cobalt edetate induced an increase in heart rate (+78 +/- 33%, p < 0.05), in cardiac output (+63 +/- 39%, p < 0.05), and in maximum rise of left ventricular pressure (+33 +/- 15%, p < 0.05), did not modify mean arterial pressure, and decreased systemic resistance (-36 +/- 15%, p < 0.05). These hemodynamic effects were associated with an increase in plasma catecholamine concentrations (epinephrine: 2524 +/- 3025 vs. 58 +/- 37 pg.ml-1, p < 0.05; norepinephrine: 1106 +/- 609 vs. 343 +/- 146 pg.ml-1, p < 0.05), which in contrast remained unchanged after hydroxocobalamin administration. Cobalt edetate also induced an increase in blood glucose concentrations (9.9 +/- 1.9 vs. 6.1 +/- 1.2 mmol.l-1, p < 0.05) and a moderate metabolic acidosis, whereas hydroxocobalamin did not. After adrenergic (alpha 1, beta) and cholinergic receptor blockade, cobalt edetate did not modify heart rate and various indices of cardiac function, suggesting that it has no direct cardiac effects. CONCLUSION: Considering its lack of hemodynamically relevant effects, these results indicate that hydroxocobalamin is potentially a safer cyanide antidote than cobalt edetate. PMID- 8440795 TI - Right ventricular function in early septic shock states. AB - OBJECTIVES: To define a variable which could reliably predict when fluid resuscitation as monotherapy is not expected to improve organ perfusion pressure, owing to limitations in cardiac output responsiveness in patients with severe sepsis. DESIGN: Prospective controlled trial. SETTING: Anesthesiological ICU in a university hospital. PATIENTS: Twenty seven patients in early septic shock states (MAP < 60 mmHg). INTERVENTIONS: Infusion therapy was titrated until no further increase in cardiac index and mean arterial pressure could be achieved. Fluid resuscitation as monotherapy was deemed unsuccessful at the end of 2 h if inotropic or vasoactive pharmacologic support was required to maintain a mean arterial pressure > 60 mmHg. MEASUREMENTS AND RESULTS: We investigated the hemodynamic course during fluid resuscitation (2850 +/- 210 ml crystalloids) with special emphasis on right heart function using the thermodilution technique. Eleven patients (group A) had a right ventricular (RV) ejection fraction below 45%. In this group positive inotropic and/or vasoactive drugs were obligatory to achieve and maintain a sufficient perfusion pressure (MAP > 60 mmHg) after fluid challenge. CONCLUSIONS: In 27 septic shock patients investigated, we diagnosed right ventricular dysfunction in 41%. In this specific patient population fluid replacement alone did not succeed in stabilizing hemodynamic variables, therefore necessitating catecholamine therapy. PMID- 8440796 TI - Inflation static pressure-volume curves of the total respiratory system determined without any instrumentation other than the mechanical ventilator. AB - OBJECTIVE: To assess the accuracy of static pressure-volume (PV) curves of the total respiratory system performed with the data directly obtained from the Servo 900 C vs. the data obtained from an external calibrated device. DESIGN: Performance of the PV curve by the method of Levy with simultaneous recording of data obtained from both systems. SETTING: The general ICU of Hospital de Sabadell. PATIENTS: Ten sedated and paralyzed patients ventilated in the control mode for acute respiratory failure were evaluated. INTERVENTIONS AND MEASUREMENTS: Inflation static PV curves were performed by the method of Levy. We simultaneously measured airway pressure and volume by means of calibrated pressure transducer and pneumotachograph and by the internal devices built in the ventilator Siemens Servo 900 C. Statistics were concordance analysis between the two methods and covariance analysis between derived curves. RESULTS: concordance analysis between both methods showed a 95% confidence interval of (+4%, -5%) in volume and (+2.2 cmH2O, -1.7 cmH2O) in pressure. Derived PV curves analyzed by MANOVA showed no significant differences whichever the method used within subject (p = 0.579). CONCLUSION: Inflation static pressure volume curves of the total respiratory system can be accurately performed with the data directly obtained from the Servo Ventilator 900 C without the need of any other external device. PMID- 8440797 TI - Prediction equation estimates of creatinine clearance in the intensive care unit. AB - OBJECTIVE: To assess the accuracy of 4 mathematical equations used to estimate creatinine clearance versus the 24-h creatinine clearance in ICU patients. DESIGN: Prospective study of renal function prediction. SETTING: The general adult ICUs of 3 metropolitan hospitals. PATIENTS: 199 critically ill patients with indwelling foley catheters. INTERVENTION AND MEASUREMENTS: Routine 24 h creatinine clearances were evaluated only in patients whose urine volume recorded by the nurses was within 10% of the laboratory's measured volume. Four mathematical equations utilizing age, sex, body weight, height, and plasma creatinine were used as a comparison. There was no difference in estimated creatinine clearance by 3 published methods when the 24 h creatinine clearance exceeded 100 ml/min. When the 24 h creatinine clearance was less than 100 ml/min, however, one prediction equation adjusted for lean body weight (LBW), was the most accurate. This equation accurately predicted creatinine clearance in the range of 30-100 ml/min and slightly overestimated creatinine clearance at 0-30 ml/min (p < 0.01, ANOVA all groups, p < 0.05 Fisher and Scheffe post-hoc tests) with a mean difference +/- 95% confidence interval of -5 +/- 3.1 ml/min. CONCLUSION: An initial rapid estimate of creatinine clearance in critically ill ICU patients with reduced renal function can be determined by an equation adjusted for LBW. PMID- 8440798 TI - Does platelet size correlate with function in patients undergoing cardiac surgery? AB - OBJECTIVE: Platelet dysfunction secondary to cardiopulmonary bypass (CPB) is one of the major reasons for nonsurgical post-operative bleeding in cardiac surgery. Whether platelet size is an indicator for platelet function was investigated in patients undergoing coronary artery bypass grafting. DESIGN: Prospective study. SETTING: Intra-operative, cardiac surgery operations. PATIENTS: 80 consecutive patients undergoing coronary artery bypass grafting. Excluding criteria were pre operative coagulation disorders and medication with anticoagulants within the last 10 days before the operation day. MEASUREMENTS AND RESULTS: Platelet function was assessed by aggregometry using a turbidimetric method (inductors: ADP 2.0 mumol/l, collagen 4 micrograms/l, epinephrine 25 mumol/l). Mean platelet volume (MPV) was measured by an electrical conductivity method. Measurements were carried out before, during, and after CPB until the 1st post-operative day on intensive care unit (ICU). Platelet size decreased significantly during CPB (max. -25% after weaning from bypass) and returned to baseline values on the 1st post operative day. Platelet count (ranging from 93 - 304 x 10(9)/l) did not correlate significantly with MPV or aggregation variables. Maximum aggregation and maximum gradient of aggregation induced by ADP and collagen were significantly decreased by CPB with the most pronounced reduction at the end of CPB (ranging from -25% to -45%). Analyses of co-variance revealed a significant correlation between changes in MPV and changes in aggregation variables (ADP, collagen). CONCLUSIONS: Platelet volume is easy to measure even in the operation room or in ICU and may indicate abnormalities in platelet function in the post-bypass period of cardiac surgery patients. PMID- 8440799 TI - Management of atrial tachyarrhythmias in the critically ill: a comparison of intravenous procainamide and amiodarone. AB - OBJECTIVE: To compare the efficacy and safety of intravenous (IV) amiodarone and procainamide for the treatment of atrial tachyarrhythmias (AT) in the critically ill. DESIGN: In this prospective study, patients were allocated to drug treatment on the basis of hospital identification number, even for procainamide and odd for amiodarone. SETTING: Patients were recruited from a teaching hospital ICU and did not include postoperative cardiac patients. PATIENTS AND PARTICIPANTS: 26 patients with AT sustained for at least 1 h and failure to respond to correction of possible precipitating factors were entered in the study. Exclusion criteria were systolic blood pressure (SBP) < 80 mmHg, and known hypersensitivity to either drug. Two patients with chronic atrial fibrillation (who received amiodarone) were later excluded from the analysis. In the final analysis, 14 patients received procainamide and 10 amiodarone. INTERVENTIONS: IV amiodarone (3 mg/kg followed by 10 mg/kg/24 h, with repeat dose of 3 mg/kg at 1 h if no response) or i.v. procainamide (10 mg/kg at 1 mg/kg/min followed by infusion of 2 4 mg/min for 24 h, with repeat dose of 5 mg/kg at 1 h if no response). MEASUREMENTS AND RESULTS: In the procainamide group 10/14 (71%) and in the amiodarone group 7/10 (70%) had converted to sinus rhythm by 12 h. There was no significant difference in response between the groups. SBP was not significantly different from baseline after administration of either drug. CONCLUSIONS: Procainamide and amiodarone appear to be safe and equally effective in the treatment of AT in the critically ill. PMID- 8440800 TI - Group A beta-haemolytic streptococcus septicaemia: the toxic strep syndrome. Report of our cases developing septic shock and multiple organ failure. AB - During the last two decades, severe group A beta-haemolytic streptococcal infections have been defined as the "toxic strep syndrome", and have been reported not only in immunocompromised or elderly people, but also occasionally in previously healthy patients. We describe 4 patients presenting with the toxic strep syndrome, requiring surgery and intensive care, and briefly review the related literature. Fatigue, localized pain and other nonspecific symptoms were associated with the onset of the disease, followed by septic shock with multiple organ failure. Early diagnosis and surgical intervention, if necessary, are mandatory. Subsequently, appropriate supportive treatment of vital organ dysfunction and penicillin as the antibiotic of choice represent the cornerstones of the management of this syndrome. PMID- 8440801 TI - Sotalol poisoning associated with asystole. AB - Sotalol overdose has special features because this beta-blocker has the potential to lengthen the Q-T interval and to initiate severe arrhythmias such as ventricular tachycardia or fibrillation. We describe the case of a 70-year-old woman who ingested 6.72 g sotalol with suicide attempt. Despite administration of activated charcoal, glucagon, atropine and isoprenaline, two episodes of asystole occurred, requiring cardiopulmonary resuscitation. Further treatment included ventricular pacing and dopamine. The patient recovered without neurologic nor cardiac sequelae. PMID- 8440802 TI - Treatment of severe tetanus by intrathecal infusion of baclofen. PMID- 8440803 TI - Traumatic perforation of the cervical esophagus: a complication of endotracheal intubation. PMID- 8440804 TI - Influence of constant sustained positive airway pressure on right ventricular performance. AB - OBJECTIVE: The detrimental effect of positive airway pressure on right ventricular (RV) performance is controversial and the aim of this study was to determine the effects of constant positive airway pressure without ventilatory fluctuation on RV performance with the aid of a pulmonary arterial catheter equipped with a rapid response thermistor for measuring RV ejection fraction (RVEF) and RV end-diastolic volume index (RVEDVI). DESIGN: A prospective, clinical study. SETTING: The central operating theatre of a university hospital. PATIENTS: Nine patients who had major surgery and required right heart catheterization for normal clinical management. MEASUREMENTS AND RESULTS: Cold indicator was injected into the RV 4 or 5 times for each airway pressure (0, 10 or 20 cmH2O) which was maintained manually stable for 15 s, and 9 paired data were analyzed by repeated-measures analysis of variance. They are separated into two groups; RVEF at zero airway pressure greater (A group) or less (B group) than 0.4. In A group (7 patients), increasing airway pressures (0 vs 10 vs 20 cmH2O) did not affect RVEF (0.55 +/- 0.05 vs 0.54 +/- 0.06 vs 0.56 +/- 0.04), RVEDVI (69 +/- 36 vs 73 +/- 29 vs 58 +/- 20 ml.m-2), or stroke volume index (SVI: 38 +/- 18 vs 40 +/- 17 vs 33 +/- 13 ml.beat-1.m-2); however, in B (2 patients), RVEF (0.35 and 0.38 vs 0.31 and 0.28 vs 0.19 and 0.17) and SVI (35 and 28 vs 32 and 27 vs 27 and 23) decreased, while RVEDVI increased (99 and 73 vs 103 and 97 vs 146 and 132). CONCLUSIONS: In most patients, the changes in RVEF, SVI, and RVEDVI did not occur under constant positive airway pressure, therefore the changes reported in mechanically ventilated patients may not attributable to the extent of positive airway pressure but rather to abrupt increases in airway pressure. These appears, however, to be patients whose RV function is so disturbed that they cannot cope with increased afterloads. PMID- 8440805 TI - Specificity of interpersonal sensitivity to non-melancholic depression. AB - Scores of 69 remitted depressed patients were compared to control subjects on the Interpersonal Sensitivity Measure (IPSM). The patients were categorised into melancholic and non-melancholic sub-groups according to DSM-III criteria. Differences between the depressives and controls were detected but were principally the result of high IPSM scores being returned by the non-melancholic depressives. Melancholic depressives did not differ from the controls in their IPSM scores, supporting the proposition that this depressive sub-type is not associated with a vulnerable personality style. PMID- 8440806 TI - Therapy and prevention of affective illness by total sleep deprivation. AB - The therapeutic effect of total sleep deprivation (SD) given twice a week, for 4 weeks, was investigated in 16 drug-free patients with major affective disorders. The response was excellent in five patients, satisfactory in three and minimal in eight patients. Six of these patients were treated prophylactically once a week, and four had an excellent response. Additionally, out of five normothymic drug free patients with affective illness treated prophylactically with SD, without prior therapeutic SD treatment, three had an excellent response. The majority of responders were rapid cycling patients. This method is worth applying to patients resistant to classical treatment. PMID- 8440807 TI - Suicidal behavior in bipolar and unipolar affective disorders: a meta-analysis. AB - A meta-analysis of studies of suicidal behavior in patients with bipolar and unipolar affective disorders found two possible trends: an excess of subsequent completed suicide in unipolar patients and an excess of subsequent attempted suicide in bipolar patients. Suggestions were made for future research. PMID- 8440808 TI - Do reversed depressive symptoms occur together as a syndrome? AB - Although the DSM-IIIR diagnostic criteria for major depression include hypersomnia, increase in appetite, and in children and in adolescents irritability, there is no general agreement on the existence of a depressive syndrome with reversed vegetative symptoms. Our findings suggest that these reversed depressive symptoms may not occur together as a syndrome. However, they may share an enhanced responsiveness to moclobemide treatment. PMID- 8440809 TI - DSM-III-R personality disorders in a mood and anxiety disorders clinic: prevalence, comorbidity, and clinical correlates. AB - This study examined the prevalence, comorbidity, and clinical correlates of personality disorders in an outpatient sample (N = 352) with anxiety and depression. Subjects were diagnosed using the Structured Clinical Interview for DSM-III-R (SCID) on Axes I and II, and they also completed interview and self report measures of symptoms. Subjects with a personality disorder were less likely to be married, more likely to be single or divorced, had lower family incomes, had more severe symptoms of both anxiety and depression, and had a greater number of lifetime Axis I diagnoses. Subjects with dysthymic and bipolar disorders were more likely, and subjects with panic disorder uncomplicated by agoraphobia were less likely to have a personality disorder compared to the rest of the sample. The most prevalent personality disorders were Avoidant, Obsessive Compulsive, Paranoid, and Borderline. Paranoid co-occurred with Narcissistic, and Borderline co-occurred with Histrionic personality disorder significantly more often than chance and base rates would predict. PMID- 8440810 TI - Comparison of primary and secondary panic disorder: a preliminary report. AB - We examined the onsets of comorbid psychiatric disorders in patients with panic disorder (PD) (N = 54). In 42 patients (77.8%), PD was preceded by another psychiatric condition (secondary PD group), while in 12 patients (22.2%), PD occurred first or was the only diagnosed mental disorder (primary PD group). Patients with primary and secondary PD did not differ with respect to demographic variables, mean ages of onset of PD, mean duration of PD, number of patients with a personality disorder, and number of patients with different DSM-III-R subtypes of PD. Except for the anger and sleep scales of the Hopkins Symptom Checklist 90, patients with primary PD had significantly less self-rated psychopathology; they also displayed less extensive phobic avoidance, and had a lower rate of current psychiatric comorbidity. These findings are discussed in light of the value of the concepts of comorbidity and primary/secondary dichotomy. PMID- 8440811 TI - Nutritional correlates of atrophic glossitis: possible role of vitamin E in papillary atrophy. AB - Atrophy of the filiform papillae of the tongue is a sign of malnutrition. However, papillary atrophy has not been correlated with laboratory indices of nutritional status. We studied photographs of tongues from 30 elderly subjects and determined the percentage of normal papillary development (%NPD) relative to a reference photograph. We also determined 16 nutritional blood levels and used stepwise multiple linear regression to examine their relationship to %NPD. We found that %NPD correlated significantly (p < 0.0031) with levels of vitamin E and prealbumin, but not with 14 other laboratory indices. Subjects with overt atrophic glossitis (%NPD < 50%) tended to have multiple nutritional deficiencies. The high correlation of plasma vitamin E levels with %NPD may be related to its role as an antioxidant and in the maintenance of cellular membrane integrity. PMID- 8440812 TI - Viewpoint on the Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults. PMID- 8440813 TI - Magnesium deficiency affects malaria susceptibility in mice. AB - One hundred twenty mice were fed control and magnesium-(Mg) deficient diets containing 960 and 50 mg Mg/kg, respectively. After 12 days, mice were inoculated with several strains of Plasmodium (P). Parasitemias and survivals were monitored for 20 days after infection. The Mg-deficient diet protected mice against the nonlethal parasite P. chabaudi as shown by decreased parasitemia. All control mice infected with P. vinckei died from the infection. Mg-deficient mice had a much lower parasitemia and recovered from the infection. In mice infected with the lethal strain P. berghei, the parasitemia showed a biphasic response. In control mice, the first phase resulted in the death of 40% of the animals. After a spontaneous reduction of parasitemia, the surviving animals showed a second increase in parasitemia, which resulted in the death of the remaining animals. In the deficient group, all the animals survived the first phase of infection. By contrast, the evolution of the second phase was similar to that observed in controls. Examination of blood smears showed that the second phase corresponded to an invasion of young reticulocytes by the parasite. The results suggest that the protective effect of Mg deficiency is related to the decrease in erythrocyte Mg and to the prooxidative effect of this mineral deficiency in mature erythrocytes. PMID- 8440814 TI - Treatment of Wilson's disease with zinc: XI. Interaction with other anticopper agents. AB - Zinc (Zn) is increasingly being used as a treatment for Wilson's disease. Some physicians have been prescribing Zn in conjunction with other anticopper agents, such as penicillamine or trien, although theoretically these drugs might be antagonistic in their effects. In addition, Wilson's disease patients quite often take vitamin C in high doses in conjunction with Zn therapy, and there are indications of possible interactions among vitamin C, Zn and copper (Cu). Interactions of penicillamine, trien, and vitamin C with Zn have not been previously studied in terms of the potential effects of these agents on Zn efficacy in Wilson's disease. Here we have studied these interactions in the maintenance phase of therapy, using Cu balance and absorption of orally administered 64Cu as endpoints. We find evidence for probable interactions of both penicillamine and trien with Zn; however, the end result on Cu balance is about the same with Zn alone as it is with Zn plus one of the other agents. Thus, there appear to be no advantages to concomitant administration. We find no detectable interaction of Zn and vitamin C on Cu balance, when vitamin C is taken in daily doses of 1000 mg. PMID- 8440815 TI - The relationship between placental cadmium, zinc, and copper. AB - A number of interactions between the essential metals zinc (Zn) and copper (Cu), and the toxic metal cadmium (Cd), have been described in animal, but not in human tissues. The purpose of this study was to determine whether Cd levels are directly related to Zn or Cu levels in the human placenta at term, and whether this relationship is affected by parity or smoking. Atomic absorption spectroscopy was used to determine Cd, Zn and Cu in perfused placental cotyledons from 292 low-risk parturients. Plasma thiocyanate levels were used to determine smoking status. Linear regression and repeated measures analysis of variance (ANOVA) were used to examine relationships between the elements and the effects of parity and smoking status. Results show significant correlations between placental Cd and both Zn (r-0.41; p < 0.01) and Cu (r-0.35; p < 0.01), but only in multiparous patients. These relationships were not altered by smoking. These results suggest that Cd-Zn and Cd-Cu interactions occur in the placenta at "normal" levels of Cd exposure and over a very short time period. PMID- 8440816 TI - The effect of fat and carbohydrate on plasma glucose, insulin, C-peptide, and triglycerides in normal male subjects. AB - Ten normal subjects were given 50 g starch, or 50 g starch + 50 g fat as a breakfast meal. The starch was given in the form of potato; the fat was given in the form of butter. The meals were ingested at 8 a.m. Plasma glucose, insulin, C peptide, and triglyceride concentrations were measured at various time points for 4 hours after each meal. The net 4-hour postprandial area responses to the ingested meals were determined using the trapezoid rule, with the fasting glucose concentration, measured at the same time points for 4 hours as a baseline. The glucose area response was 2.2 mmol hour/l following the potato meal. This was significantly reduced following ingestion of the meal containing fat (1.3 mmol hour/l) (p < 0.01). The insulin area response was slightly greater following the meal containing fat (459 pmol hour/l) compared to potato alone (423 pmol hour/l) (p < 0.01). The C-peptide area response following the meal containing fat was 0.80 pmol hour/ml, clearly greater than following potato alone (0.58 pmol hour/ml) (p < 0.01). The triglyceride area response also was much greater following the meal containing fat compared to potato alone (0.74 and 0.08 mmol hour/l, respectively). The mechanism of the attenuated glucose response to carbohydrate ingestion with a fat-containing meal is unknown. It may be due to the release of an enteric hormone that increases glucose disposal, either directly or indirectly, through insulin. PMID- 8440817 TI - Relationship between dietary protein intake and serum urea, uric acid and creatinine, and 24-hour urinary creatinine excretion: the BIRNH Study. AB - Relationships between dietary protein intake of a large free-living group and serum creatinine (Cr), urea and uric acid levels have been studied, based on data obtained from the BIRNH (Belgian Interuniversity Research on Nutrition and Health) study. Highly significant correlations were found in both sexes for total protein, as well as for animal and vegetable protein intake. In a subgroup, the relationship between dietary protein intake and 24-hour urinary Cr excretion has also been studied. The range of +/- 2 SD of the mean for total protein and animal and vegetable protein daily intakes resulted in a calculated range of 24-hour Cr excretion of 430, 317 and 209 mg/24 hours in men and of 192, 169 and 125 mg/24 hours in women, respectively. The 24-hour urinary Cr excretion was significantly influenced by both dietary protein and polyunsaturated fat intake. PMID- 8440818 TI - Metabolism of triglyceride-rich emulsions in rats with protein malnutrition. AB - Knowledge of chylomicron metabolism is very important in understanding and treating protein malnutrition, since these particles are the primary carriers of dietary fat in lymph and plasma. In the bloodstream, fat transported in chylomicrons is hydrolyzed by the action of lipoprotein lipase and the resulting fatty acids and glycerol are taken up by the body tissues. Chylomicron remnants are then rapidly removed by the liver. To clarify chylomicron metabolism in protein malnutrition, triglyceride-rich emulsions known to behave metabolically like lymph chylomicrons and labeled with 14C-cholesteryl ester and 3H triglycerides were injected intraarterially into control rats and rats fed a protein-deficient diet for 40 days. Plasma kinetics and organ uptakes of the labeled lipids were determined. Hydrolysis of the emulsion triglycerides by lipoprotein lipase was not different in the malnourished rats (TG-FCR = 0.250 +/- 0.027 m-1 vs 0.250 +/- 0.070 m-1 in controls), but plasma clearance of the resulting triglyceride-depleted emulsion remnant particles was markedly lower compared to controls (cholesteryl-ester FCR = 0.088 +/- 0.009 and 0.146 +/- 0.019 m-1, respectively, p < 0.001). These results were obtained regardless of the amount of emulsion lipid that was injected. Liver atrophy seem to account for the delayed remnant uptake in protein-depleted rats. These data provide insight into the consequences of parenteral nutrition with lipid emulsions when administered in states of protein malnutrition. PMID- 8440819 TI - A histomorphometric comparison of bone in young growing rats fed an elemental diet versus a chemically defined polymeric diet. AB - This study was designed to examine whether a synthetic elemental diet, which could be adapted for total parenteral nutrition, is capable of promoting bone growth comparable to a commercially available liquid polymeric diet. The orally fed young rat was chosen as a model of rapid bone growth. Sixteen male, Wag/Rij rats weighing 120 +/- 3 g were divided into two groups of eight rats each. One group was fed an elemental diet formulated to approximate the nutritional requirements of the rat as recommended by the National Research Council. The comparison group received a liquid polymeric diet. After 14 days there were no significant differences between groups in femur and tibia weights, cortical and medullary area, periosteal and endosteal label area, growth plate width, percent cancellous bone, bone apposition rates and osteoblasts and osteoclasts per millimeter. Both groups maintained a positive calcium and nitrogen balance. These data indicate that bone growth, structure and remodeling comparable to that seen in a polymeric-fed comparison group can be achieved in young rats when fed an oral dextrose/amino acid-based elemental solution for 2 weeks. PMID- 8440820 TI - Zinc kinetics in patients with bone demineralization due to physical immobilization. AB - To examine the relationship between zinc (Zn) status and bone demineralization, a body Zn kinetics study was performed with 74 (37 male, 37 female) disabled persons ranging in age from 16 to 45 years. Three groups were classified according to degree of limited mobility: group 1 (n = 23), capable of walking; group 2 (n = 20), capable of crawling; group 3 (n = 31), bed-ridden, Serum Zn levels were similar in the three groups, whereas body Zn clearance and the distribution of Zn showed a pattern [group 1 < group 2 < group 3 (p < 0.01, p < 0.05)], with the reverse in cases of bone mineral density (BMD) [group 1 > group 2 > group 3 (p < 0.01)]. Renal handling of Zn did not different among the three groups. There was a negative correlation between Zn distribution volume and values of BMD (p < 0.005, gamma = 0.387). Thus, various organs, as well as the skeleton, are Zn deficient in immobilized patients. PMID- 8440821 TI - Brief communication: effect of pharmacologic doses of vitamin B6 on carpal tunnel syndrome, electroencephalographic results, and pain. AB - The role of vitamin B6 as a therapeutic agent in the treatment of carpal tunnel syndrome was examined by monitoring both the standard clinical and electrophysiological parameters for entrapment neuropathy at the wrist. Electroencephalogram (EEG) studies were done in an attempt to identify patients most likely to benefit from B6 treatment. EEGs did not prove useful as predictors of clinical response to vitamin B6. Our patients, however, did not show any abnormalities prior to treatment, and no changes occurred during the treatment period. Motor latency, while the most common screening test for carpal tunnel syndrome, was not significantly changed during the course of treatment. It did not prove to be a useful test for monitoring clinical effectiveness of the treatment. Parameters showing the greatest changes were pain scores and sensory latency, which most closely paralleled clinical assessments. Pain scores, more than any other parameters, were improved in these patients following vitamin B6 treatment. Vitamin B6 has been shown to change pain thresholds in clinical and laboratory studies. This may be the basis of the significant improvement in pain scores when electrophysiologic data showed only mild improvement. This study suggests that vitamin B6 deficiency may not be a cause of carpal tunnel syndrome in spite of the observed therapeutic effect, without toxicity, of vitamin B6 treatment. PMID- 8440822 TI - Vitamin A status of alcoholics upon admission and after two weeks of hospitalization. AB - The purpose of this study was to determine the vitamin A status of alcoholics upon admission and after a brief in-patient stay. Fasting blood was drawn from 28 randomly selected subjects who were presumed to represent a wide range of liver disease severity. Admission laboratory tests revealed hypozincemia in 14.8% of subjects, while serum retinol and retinol-binding protein (RBP) were depressed below normal range in 15 (57.1%) and 7 (25%) of the subjects, respectively. Significant linear correlations were found between serum retinol and RBP (r = 0.90, p < or = 0.0001), serum retinol and albumin (r = 0.76, p < or = 0.0001), serum retinol and serum zinc (r = 0.56, p < or = 0.0003), and serum retinol and serum triglycerides (r = 0.42, p < or = 0.006). All subjects with elevated serum bilirubin levels demonstrated depressed serum retinol levels. However, elevated molar ratios of retinol to RBP suggest that the carrying capacity of RBP was at times exceeded, even with low serum retinol levels. Follow-up of 12 subject after 2 weeks of hospitalization revealed significant individual changes in blood chemistry, but no general trends. Although this study emphasizes the need for individual evaluation and treatment, elevated bilirubin levels may be indicative of low serum retinol levels in the alcoholic. Caution in levels of vitamin A therapy in these cases is advised, and consideration should instead be given to beta-carotene supplementation. PMID- 8440823 TI - To: President Clinton. Re: combating childhood obesity. PMID- 8440824 TI - Making our voices heard about the global effects of gender bias. PMID- 8440825 TI - Implementing the Americans with Disabilities Act. PMID- 8440826 TI - Carotenoid content of fruits and vegetables: an evaluation of analytic data. AB - The test of the association between dietary intake of specific carotenoids and disease incidence requires the availability of accurate and current food composition data for individual carotenoids. To generate a carotenoid database, an artificial intelligence system was developed to evaluate data for carotenoid content of food in five general categories, namely, number of samples, analytic method, sample handling, sampling plan, and analytic quality control. Within these categories, criteria have been created to rate analytic data for beta carotene, alpha-carotene, lutein, lycopene, and beta-cryptoxanthin in fruits and vegetables. These carotenoids are also found in human blood. Following the evaluation of data, acceptable values for each carotenoid in the foods were combined to generate a database of 120 foods. The database includes the food description; median, minimum, and maximum values for the specific carotenoids in each food; the number of acceptable values and their references; and a confidence code, which is an indicator of the reliability of a specific carotenoid value for a food. The carotenoid database can be used to estimate the intake of specific carotenoids in order to examine the association between dietary carotenoids and disease incidence. PMID- 8440827 TI - Feeding practices and nutrition recommendations for infants with cystic fibrosis. AB - Cystic fibrosis (CF) is an autosomal recessive disease characterized clinically by recurrent respiratory tract infections and malabsorption caused by pancreatic insufficiency. Typically diagnosed during infancy or childhood, CF impairs weight gain and growth, increases susceptibility to infection, and decreases longevity. Until recently, no guidelines for infant feedings were available. A consensus report prepared through the Cystic Fibrosis Foundation summarizes guidelines for the optimal nutrition management of patients with CF. This study identified current feeding practices and nutrition recommendations of dietitians who treat infants with CF and compared them with the recommendations of the consensus report. A survey was developed and sent to dietitians (n = 130) who work in accredited cystic fibrosis centers. Eighty-six dietitians (66%) responded after two mailings, and 75 usable surveys were analyzed. The survey investigated practitioners' recommendations for infant formulas, energy intake, nutritional supplements, and pancreatic enzyme supplementation. Protein hydrolysate infant formulas were recommended by most respondents (69%). Energy intake greater than 130% of the Recommended Dietary Allowances (RDAs) was recommended for well nourished infants with CF and greater than 140% of the RDAs for malnourished infants with CF at 1 year of age. Formula additives, including fat and carbohydrate modules, were used by all respondents and were frequently added to infant foods to increase caloric density. Enteric coated pancreatic enzymes were used by the majority (76%) of dietitians. These findings indicate that most dietitians follow the nutrition guidelines established by the Cystic Fibrosis Foundation consensus report for goals for energy and protein intake, use of nutritional supplements, and replacement of pancreatic enzymes in infants with CF. PMID- 8440828 TI - A survey of dietetics professionals' knowledge of and attitudes toward cholesterol management. AB - Dietetics professionals in Wisconsin (n = 687) were surveyed to assess their knowledge, attitudes, practices, experience, and educational interests regarding cholesterol management. The survey, conducted to guide the development of cholesterol education programming in the state, found that most dietetics professionals are familiar with and support the guidelines of the National Cholesterol Education Program (NCEP). Ninety-three percent of dietetics professionals responding to the survey believe that reducing serum cholesterol levels will reduce the risk of heart disease; the same percentage of respondents were familiar with NCEP guidelines for detecting and treating blood cholesterol levels and knew which cholesterol levels should be treated. Seventy-three percent were familiar with the American Heart Association step 1 diet, and 69% were familiar with the step 2 diet. On average, survey respondents defined a cholesterol level of 6.12 mmol/L as "high risk"; this value is almost identical to the NCEP definition. Respondents were optimistic about patients' ability to reduce their blood cholesterol levels through dietary modifications. Dietetics professionals are interested in education on cholesterol management, although individual educational interests vary depending on the respondent's area of practice. PMID- 8440829 TI - Standards of Practice criteria: consultant dietitians in health care facilities. AB - Establishment of quality assurance guidelines is becoming increasingly necessary in long-term-care facilities. The Consultant Dietitians in Health Care Facilities (CD-HCF) dietetic practice group of The American Dietetic Association (ADA) developed 27 documentations/outcome-oriented guidelines for quality assurance. The documentations were categorized according to the six Standards of Practice developed by ADA. The six general categories covered establishment of performance criteria, development of individual practice plans, knowledge of nutrition, self development, research, and use of resources. We surveyed 188 members of the CD HCF about their levels of agreement in theory with and frequency of completion for each documentation. Of the respondents, 165 (88%) were employed in long-term care facilities. Respondents had worked as consultant dietitians for a mean of 10 years. Four standards and the total questionnaire had highly significant positive correlations between agreement in theory and frequency of completion. The findings indicate that consultant dietitians agree with the theory of the documentation and frequently complete documentation. PMID- 8440830 TI - The development and application of a carotenoid database for fruits, vegetables, and selected multicomponent foods. AB - A carotenoid database for individual and multicomponent foods has been compiled that contains values for the five most common carotenoids (alpha-carotene, beta carotene, beta-cryptoxanthin, lycopene, lutein) in 2,458 fruits, vegetables, and multicomponent foods containing fruits and vegetables. The database was used to estimate intakes of specific carotenoids for 19- to 50-year-old women (n = 1,102), using food consumption data obtained from dietary recalls in the US Department of Agriculture Continuing Survey of Food Intake by Individuals, 1986. The major contributors of alpha-carotene were carrots consumed as a single food or as an ingredient in multicomponent foods. Carrots, cantaloupe, and broccoli were the main sources of beta-carotene. Orange juices and blends, oranges, and tangerines were important contributors of beta-cryptoxanthin. Tomatoes and tomato products consumed as single foods or as ingredients in multicomponent foods provided most of the dietary lycopene. Contributors of lutein + zeaxanthin included collard, mustard, or turnip greens; spinach; and broccoli. The per capita consumption of total carotenoids (the sum of the five specific carotenoids) among these women was approximately 6 mg/day. PMID- 8440831 TI - A nutrition counseling workshop: integrating counseling psychology into nutrition practice. PMID- 8440832 TI - Attitudes of long-term-care foodservice staff toward older workers. PMID- 8440833 TI - Galactose content of selected fruit and vegetable baby foods: implications for infants on galactose-restricted diets. PMID- 8440834 TI - Assessment of the food perceptions of university students. PMID- 8440835 TI - Position of the American Dietetic Association: child nutrition services. PMID- 8440836 TI - Health care reform--making nutrition part of the package. PMID- 8440837 TI - Clinical indicators for oncology, cardiovascular, and surgical patients: report of the ADA Council on Practice Quality Assurance Committee. AB - Clinical indicators were developed as an ADA project for use by the membership and the Joint Commission on Accreditation of Healthcare Organizations as part of its Agenda for Change. This 3-year project involved three clinical indicator task forces who developed clinical indicators for oncology, cardiovascular, and surgical adult acute-care setting patient populations. The task forces developed clinical indicators that were revised after an extensive field review and validation by field test. The following indicators were recommended: Cardiovascular--Patients at high risk for impaired nutritional status receive nutrition intervention within 5 days of admission or within consecutive 5 days on clear liquid diet/nothing by mouth; Patients make food choices consistent with therapeutic diet. Oncology--No patient is on clear-liquid diet/nothing by mouth without nutrition support for more than 5 days; All patients at moderate or high risk are identified by screening and assessed within 72 hours of admission; Patients at moderate or high risk are able to implement nutrition care plan at discharge. Surgery--No patient is on clear-liquid diet/nothing by mouth without nutrition support for more than 7 days; No patient has weight loss greater than 10% of admission weight at discharge; calorie and protein and/or volume goals for patients on enteral or parenteral nutrition are documented in the medical record; Patients on enteral or parenteral nutrition receive at least 1,000 kcal/day by the fourth day after an operation. PMID- 8440838 TI - Efficacy of heavy-resistance training for active women over sixty: muscular strength, body composition, and program adherence. AB - OBJECTIVE: To determine the effects of resistance training on muscular strength, body composition (percent fat and lean tissue mass), and program adherence in active women over 60 years of age. DESIGN: This study was designed as a stratified, randomized, non-blinded trial. Subjects were stratified into rank ordered pairs by level of physical activity according to the Blair Seven-Day Recall, then randomly assigned into either a weight-training (WT, n = 18) or control (CON, n = 18) group. PARTICIPANTS AND SETTING: Thirty-six women over the age of 60 (67.1 +/- 1.5, chi +/- SE) were recruited from the San Diego community. All subjects had to be engaging in some form of aerobic exercise at least 3 days each week for a minimum of 6 months. MEASUREMENTS AND INTERVENTION: Subjects engaged in isotonic training 3 days/week on Polaris machines at a target intensity of 80% of the 1 repetition maximum (1 RM) for three sets of seven exercises selected to train major muscle groups of the trunk and upper and lower body. The 1 RM was re-tested every 6 weeks in WT and the workload adjusted to maintain target intensity. The 1 RM was tested at 0, 12, and 24 weeks in CON. Body fatness and lean tissue mass, excluding skeletal mass, were assessed at 0 and 24 weeks by dual energy radiography using a total body scan. RESULTS: Increases in muscle strength of the weight trainers were significant for all seven exercises (5%-65%), with the greatest gains in the shoulder and trunk muscles. Percent body fat of weight trainers decreased significantly (from 38.8% to 37.9%, P < 0.05), while lean tissue mass increased by 1.5 kg (P < 0.01). No changes in body composition were observed in control subjects. Overall program adherence was 83% (15 weight trainers and 15 control women completed the study). Monthly attendance averaged 86.8 +/- 3.3%, with no incidence of injury during the training sessions. CONCLUSIONS: These data indicate that heavy-resistance weight training is safe and enjoyable for older women and that meaningful gains in muscular strength and body composition can be made even in women who are already highly active. PMID- 8440839 TI - Effect of aging on body fat. AB - OBJECTIVE: To examine the effects of aging on body fat. DESIGN: Cross-sectional comparison by age and gender. SETTING: Community health fairs, medical school, and a Department of Veterans Affairs Nursing Home Care Unit. PARTICIPANTS: Five hundred and fourteen individuals between the ages of 29-96 attending three different community health fairs; 62 first year medical students; and 121 male residents of a nursing home. INTERVENTION: None MEASUREMENTS: All underwent measurements of weight, height, and percentage body fat using the RJL Spectrum Bodycomp II Bioelectrical Impedance machine. RESULTS: Percentage body fat increased slightly between ages 20 to 39 years and 40 to 84 years. There were no significant differences noted in percentage body fat among the age groups 40-64, 65-74 and 75-84 in either males or females. There were also no significant differences noted in percentage body fat between any age groups when age-matched for body mass index. Patients over the age of 85 had significantly lower percentage body fat compared with all other age groups. Finally, nursing home patients were more likely to have a lower percentage body fat compared with the ambulatory population. CONCLUSIONS: The percentage body fat does not appear to increase significantly after the age of 40 years. In addition, the major reason for the increase in body fat in older persons appears to be weight gain rather than a true age-related increase in percentage body fat. Previous studies suggesting a marked increase in percentage body fat with advancing age have failed to correct for the presence of an increased body mass index that commonly occurs at middle age. PMID- 8440840 TI - Survival of elderly patients with transfusion-related acquired immunodeficiency syndrome. AB - OBJECTIVE: To determine the influences of age and risk group on the survival of AIDS patients. We concentrated on transfusion because it is the commonest risk factor for AIDS in patients over 70 years of age. DESIGN: Survival curve regression analysis. PARTICIPANTS: Patients aged 13 years and over with AIDS acquired through transfusion, and patients 65 years or older with AIDS as a result of intravenous drug use (IVDU). Data were obtained from the New York City Department of Health. MAIN OUTCOME: The patients were divided into four groups, ages 13-40 years, 41-64 years, and 65 years and over with AIDS as a result of transfusion, and 65 years and older with AIDS as a result of IVDU. The survivals of the three transfusion-related AIDS groups were compared, as were the 65 years and-over groups with AIDS as a result of transfusion or IVDU. AIDS-defining diagnoses between those over and under 65 years with AIDS as a result of transfusion were also compared. RESULTS: The median survival for the three transfusion-related AIDS groups were 273 days, 58 days, and 60 days, respectively. There was a significant association between shorter survival and increasing age. This was largely due to the longer survival of the patients aged 13-40 years. There was no difference in AIDS-defining diagnosis between those over and under 65 years with transfusion-related AIDS. The survival curves of the elderly with AIDS as a result of transfusion or IVDU were not different. CONCLUSION: Age over 40 years is an independent risk factor for poor survival among transfusion-related AIDS patients. Among the elderly, patients with transfusion-related AIDS have similar survivals to patients with IVDU-related AIDS. PMID- 8440841 TI - Left ventricular diastolic filling in elderly hypertensive patients. AB - OBJECTIVE: To evaluate the effects of mild to moderate hypertension and of LVH on diastolic filling and other Doppler indices in the elderly. DESIGN: Survey with a control group. SUBJECTS: Seventy-one hypertensives (34 men, 37 women) referred for echocardiograms and 32 age- and sex-matched normotensive volunteers. Thirty six of the hypertensives had LVH; 34 did not. SETTING: Echocardiographic laboratory. MEASUREMENTS: M-mode, two-dimensional, and pulsed Doppler echocardiograms. A wide variety of Doppler-derived indices of diastolic function were assessed. RESULTS: All Doppler derived indices of left ventricular diastolic filling (peak E, peak A, their ratio, EF slope, time-velocity integrals, atrial filling fraction, and isovolumic relaxation time) were similar among the three groups. CONCLUSION: Elderly mild to moderate hypertensives with or without LVH have LV diastolic filling that is normal for age. The identification of pathological diastolic dysfunction requires comparison to age-matched controls, since aging, a major factor influencing diastolic filling, can mask the effect of hypertension. PMID- 8440842 TI - How the manner of presentation of data influences older patients in determining their treatment preferences. AB - OBJECTIVE: To assess how the manner of presentation of graphic data to older patients influences their treatment preferences. DESIGN: Cross-sectional structured interviews with patients. SETTING: A university-based Department of Veterans Affairs Medical Center. PATIENTS: One hundred sixty-six consecutive patients (mean age = 64.8 years, range of ages 29-82) seen in a Department of Veterans Affairs general medicine clinic. MEASUREMENTS: Five pairs of 5-year survival curves were presented to patients. Each pair was composed of two survival curves for alternative unidentified treatments for an unidentified medical condition. Curve A (LT = better long-term, worse short-term survival) was fixed throughout all curve pairs. Curve B (ST = better short-term, worse long term survival) changed in each curve pair, showing incrementally better chances of short-term survival across the five curve pairs. Patients were randomly assigned to view the curve pairs in forward (increasing short-term survival) or backward (decreasing short-term survival) order. RESULTS: Order is a significant predictor of patients' initial preferences for the short-term survival curve (P = 0.0004) as well as their willingness to shift preferences during presentation of the five curve pairs. Patients > or = 65 were more likely to initially choose the ST curve in forward order presentation than patients < 65. More educated patients generally were less likely to prefer the ST curve under both elicitation orders. CONCLUSIONS: The data indicate that the method of eliciting patients' preferences strongly influenced their expressed preferences, and that these preferences may have predictable relationships with demographic characteristics such as age. PMID- 8440843 TI - Sex differences in the psychiatric manifestations of Alzheimer's disease. AB - OBJECTIVE: To test the null hypothesis, ie, that there are no gender differences in psychiatric problems manifest in patients with Alzheimer's disease. DESIGN: Survey. SETTING: Patients living in the community and evaluated at Alzheimer's disease and geriatric outpatient programs. PATIENTS: Three hundred twenty-eight women and 186 men clinically diagnosed with Alzheimer's disease using NINCDS/ADRDA or DSM-III-R criteria. MEASUREMENTS: Psychiatric signs and symptoms recorded following a psychiatric interview, including the Hamilton Depression Rating Scale. RESULTS: Approximately two-thirds of both men and women had psychiatric problems, but women had significantly more multiple symptoms. When pairs of symptoms were analyzed for independence, agitation was only significantly associated with paranoia in men, whereas in women agitation was significantly associated with most other psychiatric problems. CONCLUSION: The higher prevalence of multiple psychiatric problems in women may be due to many factors, including sociodemographic influences, physician bias, and/or other differences between men and women. The finding of a different pattern of association of symptoms with agitation in men and women deserves replication. PMID- 8440844 TI - Why men are interested in an evaluation for a sexual problem. AB - OBJECTIVE: To understand why men were interested in an evaluation of a perceived sexual problem. DESIGN: Survey. SETTING: Tertiary-referral VA Medical Center in Southeast Atlantic Region. PARTICIPANTS: Respondents from a 3% random sample of male veterans age 30-99 registered at a VA medical center with completed survey data (n = 427). MEASUREMENTS: A cross-sectional mailed survey. Independent variables included survey data related to emotional state, physical state, and/or demographic characteristics (marital status, race, and age). The dependent variable was interest in evaluation of a sexual problem. MAIN RESULTS: Measures of erectile function, libido, and orgasm, when entered sequentially as separate functional sets in a logistic regression analysis, have a statistically significant (P < 0.05) influence on interest in an evaluation of a sexual problem. After controlling for sexual function and emotional state, physical state did not add to predicting interest in an evaluation for a sexual problem. After controlling for all other covariates, those who were never married, non white, and elderly were less interested in an evaluation for a sexual problem (P < 0.05). CONCLUSION: Age, race, and marital status, in addition to sexual function, influence male veterans' interest in seeking clinical assessment for a sexual problem. PMID- 8440845 TI - Surface area measurement of pressure sores using wound molds and computerized imaging. AB - OBJECTIVE: To develop a method to measure wound surface area. DESIGN: Validity study. SETTING: Inpatient service. PARTICIPANTS: Four patients with decubitus ulcers. MEASUREMENTS: A new imaging process estimating wound surface area and volume by NMR spectroscopy of a mold of the pressure ulcer and a comparison measurement of volume of the mold by water displacement. Measurements made serially totalled 17. RESULTS: Measurement of the volume of the mold by the computer system correlated strongly with measurement of the volume by water displacement. Surface area of the pressure sore mold correlated strongly with volume of the mold raised to the two-thirds power. CONCLUSIONS: It is possible for the first time to measure surface area of decubitus ulcers. This may provide a way of determining accurately the dose of newly proposed topical treatments. PMID- 8440846 TI - Responsiveness of health status measures to change among older adults. AB - OBJECTIVE: This study examines the ability of commonly used self-reported health status measures to detect important changes in health (responsiveness) in older adults. DESIGN: We compared changes in health status measures over the year among subgroups of a cohort of seniors: those who experienced an intervening illness, hospitalization or increase in drug regimen, and those who didn't. Differences between the two groups in changes in the measures were quantitated using Guyatt's responsiveness statistic and receiver operating characteristic curves (ROC). SETTING: Staff model HMO. PARTICIPANTS: 1379 senior HMO enrollees who were participants in a health promotion trial and provided complete information at baseline and one year later. MEASUREMENTS: The following self-reported health status measures were evaluated: restricted activity days, bed disability days, the Medical Outcomes Study physical function scale, self-evaluated health, and a positive affect scale. MAIN RESULTS: All measures except the positive affect scale were able to discriminate significantly between seniors who were or were not hospitalized and/or reported a major illness in the intervening year. The two disability days measures showed the best responsiveness for all indicators of worsening health and included 70%-80% of the area under the ROC curves for major illness defined by hospitalization or self-report. CONCLUSIONS: Commonly used, brief self-reported physical health status measures are responsive to intervening illness among relatively healthy seniors supporting their use in longitudinal geriatric research. PMID- 8440847 TI - Effect of education on the clock-drawing dementia screen in non-demented elderly persons. AB - OBJECTIVE: To examine the effect of education on clock-drawing ability in non demented elderly persons. DESIGN, SETTING, PARTICIPANTS: Descriptive study of 187 elderly persons, 77 demented, 110 non-demented, 54 with 9+ years of education, 133 with 8 or fewer years of education, from three university medical center geriatric divisions. MEASUREMENTS: Subjects took the Folstein Mini-Mental State Exam and were asked to draw a clock showing a time of 3 o'clock. Clocks were scored using three previously described scoring scales (Shulman, Sunderland, and Wolf-Klein). Mean scores and proportions of normal and abnormal clocks were compared for well and poorly educated non-demented subjects. Sensitivities and specificities for detecting dementia were calculated. RESULTS: Mean scores of the well educated non-demented subjects were significantly better than mean scores of the poorly educated non-demented subjects on all three scales. However, proportions of abnormal clocks were not significantly different between well and poorly educated on the Wolf-Klein scale. For the poorly educated subgroup, sensitivity and specificity for detecting dementia by clock drawing were 90% and 42% by the Shulman scale, 74% and 44% by the Sunderland scale, and 48% and 90% by the Wolf-Klein scale. CONCLUSIONS: Clock-drawing ability is affected by education in non-demented elderly persons. The scoring method of Wolf-Klein is least educationally affected and maximizes specificity for detecting dementia but has low sensitivity. Educational effects make clock drawing a poor single screening test for dementia in a poorly educated population. PMID- 8440848 TI - Characteristic features of long-living patients with familial hypercholesterolemia in Japan. AB - OBJECTIVE: To assess characteristics of long-living familial hypercholesterolemics (FHs) in comparison with younger patients. DESIGN: Cross sectional study. SETTING: Lipid clinics of a university hospital and 14 related medical institutions. PATIENTS: A total of 335 heterozygous FHs including 17 patients over 70 years old. The average ages of the aged (> or = 70 years old) and the younger groups were 73.5 +/- 3.7 and 46.5 +/- 15.0 years, respectively. MEASUREMENTS: Medical history, serum lipids and apolipoproteins, and radiographic measurement of Achilles tendon xanthomas. MAIN RESULTS: Age distribution of FHs suggests shorter life of FHs compared with the general population. The age distribution of FH females was shifted to older age compared with that of FH males (P < 0.01). No significant differences were found between the levels of serum lipids and apolipoproteins in the aged and the younger groups. The thickness of the Achilles tendon was positively correlated with the product of excess total serum cholesterol and age in the patients (P < 0.01). Progression of Achilles tendon thickening was less in females than in males. A few cases of longevity could not be explained by any of the anti-atherogenic factors including female gender, a relatively low concentration of serum total cholesterol, a high concentration of HLD-cholesterol, a non-smoking habit, and a familial predisposition for longevity. CONCLUSIONS: The female gender was found to be one of the most important factors for long survival of FHs. The different progression of Achilles tendon thickening in females and males may be related to the slower development of atherosclerosis and higher survival rate of the female patients. PMID- 8440849 TI - Hospital Outcomes Project for the Elderly (HOPE): rationale and design for a prospective pooled analysis. AB - OBJECTIVE: To describe a collaborative investigation that is based on a series of six clinical studies aimed at reducing functional decline in the acutely-ill hospitalized elderly. DESIGN: A prospective, multicenter pooled analysis project involving collection of a common set of data from a group of related but distinct intervention trials with similar objectives. SETTING: Five university-affiliated hospitals and one community hospital. PARTICIPANTS: Elderly patients (age minimums from 65 to 75 years) admitted for a range of acute illnesses. INTERVENTIONS: Site-specific interventions include exercise and physical therapy; developing and implementing methods to improve detection and evaluation of delirious patients; a multidisciplinary geriatric care unit; a multidisciplinary intervention implemented in-hospital that includes some post-discharge care; and a nursing-centered geriatric care program. MAIN OUTCOME MEASURE: Functional status. CONCLUSION: The prospective, multicenter design of the Hospital Outcomes Project for the Elderly (HOPE) provides an innovative approach for analysis of hospital outcomes in the elderly. Although differences in study populations and interventions exist, qualitative comparisons across sites will enhance generalizability and will provide a great opportunity to examine consistency among the sites. The HOPE pooled analysis project will impart greater statistical power to detect the primary and secondary outcomes compared with previous single center trials that have assessed interventions related to functional decline in the hospitalized elderly. PMID- 8440850 TI - Extraneuronal manifestations of Alzheimer's disease. PMID- 8440851 TI - Discussions about limiting treatment in a geriatric clinic. AB - OBJECTIVE: Obtain detailed information about the frequency and content of discussions about withholding treatment between doctors and elderly outpatients. DESIGN: Survey. SETTING: Primary care geriatric clinic at an urban university. PARTICIPANTS: Twelve physicians and one nurse practitioner completed questionnaires for 185/198 (93.4%) patient visits. MEASUREMENTS: Questionnaires were completed by physicians after each patient visit during August 1989. Interviews were conducted with physicians who had discussed limiting life sustaining treatment with patients. RESULTS: Ten percent (n = 19) of patients seen had had discussions with their physicians about life-sustaining treatment. These patients were older and had worse prognoses as estimated by their physicians. Physicians usually raised the issue with the families of demented patients and mentioned dementia, quality of life, prognosis, and the need to make other clinical decisions as motivation for initiating discussions. The majority of patients with poor prognoses, however, had not had discussions about life support. CONCLUSIONS: Despite increasing attention given to end-of-life decisions in the medical and lay press, discussions with elderly outpatients about limiting treatment occur rarely. They are more likely when patients are older or have worse prognoses, but age, prognosis, and poor quality of life do not consistently lead physicians to raise the issue. PMID- 8440852 TI - Let the measurement fit the situation. PMID- 8440853 TI - Frailty and injuries in later life: the FICSIT trials. AB - Physical frailty and fall-related injuries present two of the biggest threats to older people's functioning and quality of life. The Frailty and Injuries: Cooperative Studies of Intervention Techniques (FICSIT) trials represent a set of eight different clinical trials concerning physical frailty and injuries in later life. This report documents the history and organization of the trials and provides an overview of the measures being collected at multiple sites and the analytic strategies to be used for multi-site investigations. PMID- 8440855 TI - Seniors' Program for Injury Control and Education. AB - The Seniors' Program for Injury Control and Education (SPICE) examines the effects of exercise and physical fitness on falls and related injuries among older persons. The design is a two-group, randomized trial with 2 years of follow up. The study is at Northwest Region of Kaiser Permanente (NWKP), a large hospital-based prepaid group practice HMO in Portland, OR. The participants are 1,323 community-living persons 65 years or older who are enrolled in NWKP and are at moderate risk of falling. A multifaceted intervention strategy uses a group approach to falls and injury prevention which includes moderate intensity endurance-building exercise (walking), strength and balance training, home safety improvements, and mental practice. Sessions of 20-25 participants are led by two nurses. Participants set their own realistic goals for exercising to accommodate to differing functional abilities and baseline conditioning. The control group receives usual care from the HMO. Participants report all falls for 2 years after randomization. Outcome measures include health status, physical functioning, falls, and fall-related medical care use and cost. If SPICE is effective, cost effectiveness analysis will examine the relative efficiency of SPICE versus other successful FICSIT interventions. Thus far, recruitment and intervention compliance goals have been met from a population of frail elderly HMO members. PMID- 8440854 TI - Development of the common data base for the FICSIT trials. AB - The eight FICSIT (Frailty and Injuries: Cooperative Studies of Intervention Techniques) sites test different intervention strategies in selected target groups of older adults. To compare the relative potential of these interventions to reduce frailty and fall-related injuries, all sites share certain descriptive (risk-adjustment) measures and outcome measures. This article describes the shared measures, which are referred to as the FICSIT Common Data Base (CDB). The description is divided into four sections according to the four FICSIT committees responsible for the CDB: (1) psychosocial health and demographic measures; (2) physical health measures; (3) fall-related measures; and (4) cost and cost effectiveness measures. Because the structure of the FICSIT trial is unusual, the CDB should expedite secondary analyses of various research questions dealing with frailty and falls. PMID- 8440856 TI - Yale FICSIT: risk factor abatement strategy for fall prevention. AB - Based on finding a strong association between number of impairments and risk of falling in earlier studies, Yale FICSIT investigators are conducting an intervention trial comparing the effectiveness of usual care plus social visits (SV) and a targeted risk abatement intervention (TI) strategy in reducing falls among at risk community elderly persons. Subjects include members of a participating HMO who are > or = 70 years of age, cognitively intact, not terminally ill, not too physically active, and possess at least one fall risk factor. The targeted risk factors include postural hypotension; sedative use; at least four targeted medications; upper and lower extremity strength and range of motion impairments; foot problems; and balance, gait, and transfer dysfunctions. The interventions include medication adjustments, behavioral change recommendations, education and training, and home-based exercise regimens targeting the identified risk factors. The interventions are carried out by the study nurse practitioner and physical therapist in TI subjects' homes. The SV subjects receive a comparable number of home visits as the TI subjects during which a structured life review is performed by social work students. The primary outcome is occurrence of falls during the 12-month followup. Secondary outcomes include change in mobility performance and fall-related efficacy. PMID- 8440857 TI - The Seattle FICSIT/MoveIt study: the effect of exercise on gait and balance in older adults. AB - While exercise is generally recommended for older adults, the specific role of exercise in preventing falls and frail health is unclear. The Seattle FICSIT/MoveIt study is a population-based, randomized, controlled trial comparing the effects of three 6-month exercise interventions (endurance training, strength training, or combined endurance and strength training), and three 3-month endurance training interventions (stationary cycle, walking, or aerobic movement). Primary study outcomes are aerobic capacity, strength, gait, balance, and physical functional status. The study enrolls adults age 68-85 who have leg weakness and impaired gait. It differs from most previous community-based exercise studies in several respects: recruitment of subjects from a defined population; eligibility criteria based upon physiologic and functional status deficits; random assignment to exercise groups; assessment of both physiologic and functional status outcomes; follow-up beyond the completion of supervised exercise; and a large sample size (Total N = 180). PMID- 8440858 TI - Effects of physical therapy on functional status of nursing home residents. AB - Nursing home residents typically have decreased functional and physical status and high health care utilization and costs. This randomized trial evaluates whether physical therapy is beneficial for frail debilitated long-stay residents of nursing homes. Subjects are recruited from a cohort of academic and community nursing home residents who have resided in the nursing home for greater than 3 months and are over age 60 and dependent in at least two activities of daily living. Subjects randomized to the intervention group receive one-on-one physical therapy sessions three times weekly for 4 months, while control group subjects receive structured social visits three times weekly to control for potential Hawthorne effects. Physical therapy sessions generally last 30 minutes and consist of functional activity and general conditioning exercises; these exercises are individually tailored to the subject's level of physical and functional disability. Prime outcome variables are physical function assessed by an observer-administered, performance-based instrument and self-perceived health status assessed by the Sickness Impact Profile. Health care utilization and associated costs are calculated for the following areas: the nursing home, hospitalizations, outpatient visits and procedures, medications, and the intervention. A cost-effectiveness ratio dividing incremental health care utilization and physical therapy intervention costs by the observed improvement in physical function is calculated. It is expected that results of this study can be used to help determine whether long-stay nursing home residents should be eligible for physical therapy. PMID- 8440859 TI - The Atlanta FICSIT study: two exercise interventions to reduce frailty in elders. AB - This study examines the effect of two different exercise approaches on balance and frailty measures among more than 200 community-dwelling individuals greater than 70 years of age. Exercises are provided for 15 weekly sessions on an individual basis for participants randomly assigned to a Balance Training group. Training consists of center-of-mass feedback displayed on a motor under static conditions, or, in later sessions, as the floor surface is moved, with eyes open or closed. This high technology interface provides instantaneous information about displacement of body weight in space so that balance can be enhanced. An alternative procedure is comparatively simple and requires little expense or space. Tai Chi Quan was originally developed as a martial arts form but has been used for centuries in China as an exercise among elderly citizens. Participants randomly assigned to this intervention meet twice weekly for 15 weeks to learn a condensation of 108 Tai Chi forms into 10 that emphasize movement components often restricted or absent with aging. A third group serves as a control for exercise interventions by meeting weekly for 15 sessions to discuss topics of interest such as memory loss, drug management, and nutrition. All subjects are screened prior to assignment, and a host of physical, behavioral, and functional measures are assessed before and after the intervention as well as 4 months later. Measurements unique to the Atlanta site include: balance with eyes closed, programmed force-distribution changes when stance is perturbed, cardiovascular assessments, WAIS, Affects Balance Scale, and a survey of home environment. PMID- 8440860 TI - The Boston FICSIT study: the effects of resistance training and nutritional supplementation on physical frailty in the oldest old. AB - Research indicates that lower extremity muscle weakness in the elderly is consistently related to impaired mobility and fall risk. Reversible components of the muscle weakness of aging include underuse syndromes and undernutrition, both of which are prevalent in nursing home populations. The Boston FICSIT study is a nursing home-based intervention to improve muscle strength through progressive resistance training of the lower extremities and/or multi-nutrient supplementation in chronically institutionalized subjects aged 70-100. Baseline measurements of falls, medical status, psychological variables, functional status, nutritional intake and status, body composition, muscle mass and morphology, muscle function, and gait and balance are taken. The nursing home residents are then randomly assigned to one of four treatment groups for 10 weeks: (1) high intensity progressive resistance training of the hip and knee extensors 3 days per week; (2) multi-nutrient supplementation with a 360-kcal high carbohydrate, low fat liquid supplement every day; (3) a combination of groups (1) and (2); and (4) a control group. Both non-supplemented groups receive a liquid placebo every day, and both non-exercising groups attend three sessions of "leisure activities" every week in order to control for the attentional aspects of the exercise and nutritional interventions. At the end of the 10-week period, all baseline measurements are re-assessed. PMID- 8440861 TI - Iowa FICSIT trial: the feasibility of elderly wearing a hip joint protective garment to reduce hip fractures. AB - Hip fractures exact a heavy toll in the elderly population. While intervention strategies are being investigated to reduce the numbers of geriatric falls and to improve the body's resiliency, the geriatric population remains at risk for the mortality and morbidity associated with fractures. The Iowa FICSIT site is investigating the feasibility of passive protection of the proximal femur through the use of hip pads. The pad is designed to disperse throughout the pad the energy created in a fall. The focus of the Iowa trial is to determine if elderly will wear hip pads for the majority of their waking hours. Thirty subjects are being recruited from each of six elderly populations who are at high risk to fall and at increased risk of injury. To facilitate compliance, the following strategies are utilized: run-in period, graduated implementation, tailoring of wearing times, and self-report of compliance. Outcome measures include compliance rates and injuries sustained during falls. PMID- 8440862 TI - Training balance and strength in the elderly to improve function. AB - Short-term exposure to altered sensory input or destabilizing platform movement results in significant improvement in sway control and inhibition of inappropriate motor responses, resulting in improved balance during repetitive testing. In addition, there is recent evidence that strength and function can be increased in both active and frail elderly who participate in strength training programs. Therefore, the hypotheses to be tested are that (1) balance training alone, or (2) strength training alone will each be capable of significantly improving balance, gait, and functional mobility, and that (3) a combined program of balance and strength training will be more effective than either approach alone. These hypotheses will be tested relative to a control group, using a 2 x 2 design (30 subjects per group), in a community-dwelling elderly at least 75 years of age. Intervention sessions of at least 45 minutes will occur three times per week for 3 months, with 6 months of follow-up, home-based Tai Chi training. The primary outcome variable is a basic measure of functional balance, ie, the occurrence of loss of balance during tilts of the support and/or movement of the visual surround. PMID- 8440863 TI - The lateral slump sign. PMID- 8440864 TI - CES-D: cutpoint or change score? PMID- 8440865 TI - The Mini-Mental State Examination. PMID- 8440866 TI - Alcohol use and falls. PMID- 8440867 TI - Paralysis metu. PMID- 8440868 TI - Total quality assurance. PMID- 8440869 TI - Acute hepatic and renal toxicity of dichlorobenzene isomers in Fischer 344 rats. AB - Studies were conducted to examine acute hepatic and renal toxicity of dichlorobenzene (DCB) structural isomers. Male Fischer 344 (F344) rats were injected with 2, 3 or 4 mmol kg-1 of 1,2-DCB, 1,3-DCB or 1,4-DCB (o-, m-, p-). Pair-fed control (PFC) animals were injected (i.p.) with corn oil (1 ml kg-1). Hepatic and renal toxicity was quantitated 24 h after injection of DCB or vehicle. Plasma transaminase (ALT/GPT) activity was increased (P < 0.05) by 1,2 DCB as a function of dose administered. Centrilobular necrosis was observed in rats treated with 1,2-DCB while morphology was relatively normal in rats treated with m- or p-DCB. Administration of (2 or 4 mmol kg-1) 1,3-DCB or 1,4-DCB did not alter kidney weight or blood urea nitrogen (BUN) levels. Renal cortical slice accumulation of p-aminohippurate (PAH) was decreased (P < 0.05) by (2 and 4 mmol kg-1) 1,3-DCB and (3 and 4 mmol kg-1) 1,2-DCB while accumulation of the cation tetraethylammonium (TEA) was decreased by 4 mmol kg-1 1,4-DCB. (TEA). The results of these studies demonstrated that ortho substitution enhanced hepatic and renal toxicity. The results also would suggest that the liver was more sensitive than the kidney for DCB toxicity. PMID- 8440870 TI - Influence of methylamine and N,N'-dimethylurea, the hydrolysis products of methyl isocyanate, on its systemic toxicity. AB - Subcutaneous administration of the LD50 dose of methyl isocyanate (MIC) to rats induced severe hyperglycaemia, lactic acidosis and uraemia in rats. Neither methylamine (MA) nor N,N'-dimethylurea (DMU), the hydrolysis products of MIC, administered in equimolar doses had any influence on these parameters except for a marginal transient increase in plasma urea by DMU. Methyl isocyanate administration led to haemoconcentration, resulting in an increase in the plasma concentration of total proteins and a decrease in both the plasma concentration of albumin and the plasma cholinesterase activity. The hydrolysis products of MIC had no influence on any of these parameters. Thus, it seems reasonable to suggest that the systemic effects of MIC are caused by MIC per se, in spite of its high hydrolytic instability. PMID- 8440871 TI - Partial contribution of biliary metabolites to nephrotoxicity, renal content and excretion of [14C]hexachloro-1,3-butadiene in rats. AB - Male Sprague Dawley rats with cannulated bile duct (BDC rats) received 100 or 200 mg kg-1 labelled hexachloro-1,3-butadiene ([14C]HCBD) by gavage 1 h (BDC1 rats) or 24 h (BDC24 rats) after surgical cannula implantation. Twenty-four hours after treatment with HCBD, rats were examined histochemically and biochemically for kidney damage. Urine, faeces, liver and kidney radioactivities were also measured in 24-h samples. Results were compared with those obtained from non-cannulated (NC) rats. Bile-duct cannulation did not completely protect against HCBD-induced kidney damage. The 24-h [14C] urinary excretion and tissue content was 30-50% lower in BDC rats compared to NC rats and correlated well with the toxicity findings. BDC1 rats appeared to be much more resistant to HCBD treatment than BDC24 rats. Since faecal [14C] radioactivity extractable by diethyl ether at neutral pH in BDC1 rats was twice that measured in BDC24 rats, the greater resistance was attributed to a higher deficiency in the gastrointestinal absorption of unchanged HCBD. The present results reveal that the biliary metabolites of HCBD are not solely responsible for kidney toxicity as previously assumed. They suggest a sinusoidal efflux of the HCBD conjugates from the liver. PMID- 8440872 TI - The dermal bioavailability of radiolabelled benzo[a]pyrene from acetone or from oils of differing viscosity, assessed by DNA and protein binding. AB - Tritium-labelled benzo[a]pyrene ([3H]BaP) was applied to mouse skin in acetone or mineral oils of differing viscosity. Epidermal DNA and protein were extracted after 24 or 48 h and the degree of adduct formation determined by the radioactivity present. When [3H]BaP was applied in acetone, the degree of DNA and protein binding was around 15-20 times greater than that observed when a low viscosity oil was used as a vehicle. When applied in oils of differing viscosity, however, only a twofold difference was seen across the whole viscosity range (13.5 cSt* at 40 degrees C to 1665 cSt at 60 degrees C). From measurements made of urine and faecal radioactivity and from small-scale investigations using other routes of administration, it was clear that the grooming activity of the animals had a marked effect on skin absorption and macromolecular binding. It is possible that greater grooming activity with low-viscosity oils may explain why oil viscosity did not have a greater effect on binding levels, but further studies are needed to investigate this. These findings may have important implications in the interpretation of long-term skin painting studies and may assist in the interpretation of analytical data and short-term biological assays. PMID- 8440873 TI - Comparative study on the changes in AChE and ATPase activities in neonate and adult rat brains under thiobencarb stress. AB - Thiobencarb (S-(4-chlorobenzyl)-N,N-diethyl thiol carbamate), a dithiocarbamate herbicide, was found to cause neuronal dysfunction in adult and neonate albino rats. In general, organocarbamates exert their action by inhibiting acetylcholinesterase (AChE) activity. Thiobencarb inhibited both acetylcholinesterase and adenosine triphosphatase (ATPase) activities in rat brain. Withdrawal of thiobencarb treatment resulted in the recovery of AChE activity to a normal level, whereas there was no recovery of Na(+)-K(+)-ATPase activity in either neonate or adult rat brains. The results suggest that neuronal dysfunction caused by thiobencarb is mainly due to the inhibition of ATPase activity rather than to the inhibition of AChE activity. PMID- 8440874 TI - The renal handling of calcium and phosphorus in environmental cadmium-exposed subjects with renal dysfunction. AB - Clearance methods were used to clarify the renal handling of calcium (Ca) and phosphorus (P) in a population with renal dysfunction induced by exposure to environmental cadmium (Cd). Seventy-six Cd-exposed subjects (32 men and 44 women) and 36 non-exposed subjects (18 men and 18 women) took part in this study. Fractional excretion of P was higher in the Cd-exposed subjects than in the non exposed subjects, while that of Ca was equal to that of the non-exposed subjects. The urinary excretion rates of Ca and P tended to be lower in the Cd-exposed subjects than in the non-exposed subjects. The urinary excretion rate of Ca was closely related to creatinine clearance, while that of P was related to creatinine clearance and the percentage tubular reabsorption of phosphorus. It is thought that in Cd-induced renal dysfunction the urinary excretion of Ca depends on glomerular function, and no increased excretion of urinary Ca was observed by these clearance methods. It is also clarified that the parallelism in the urinary excretion of Ca and Na persists in Cd-exposed subjects with renal dysfunction. PMID- 8440875 TI - Evaluation of the dermal carcinogenicity of lubricant base oils by the mouse skin painting bioassay and other proposed methods. AB - Lubricant base oils are petroleum products that are predominantly derived from the vacuum distillation of crude oil. Various types of refinement can be employed during the manufacturing process, and evidence suggests that certain of the associated process streams produce skin cancer. Polycyclic aromatic compounds (PACs), some of which are considered as the causative agents, are removed, concentrated or chemically converted during the refinement process. In order to understand the effects of various types of refinement processes on carcinogenic potential, 94 oils were evaluated in the mouse epidermal cancer bioassay. This Exxon database is unique, because of the wide range of crude oils and processing histories represented. Seven processing history classifications are described, and conclusions concerning the impacts of each refinement process on dermal carcinogenicity are discussed. This research also included an evaluation of selected biological and chemical test methods for predicting carcinogenic potential. These included a modified version of the Ames test for mutagenicity, as well as analytical characterizations of the polycyclic aromatic structures in the oils. For classification purposes, a sample was considered to be carcinogenic if it resulted in the production of two or more tumor-bearing animals (in test groups of either 40 or 50 animals). The modified Ames test was considered to be positive if the mutagenicity index was > or = 2.0, and PAC analyses were similarly designated as positive or negative according to proposed guidelines. All of the alternative test methods showed similar agreement with dermal carcinogenicity bioassay data; concordance values were > or = 80%. However, each test was incorrect in ca. 10%-20% of the cases evaluated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8440876 TI - Comparative study on the effects of five benzoylphenylurea insecticides on haematological parameters in rats. AB - Five benzoylphenylurea insecticides were administered to male Wistar rats for 28 days at oral doses of 100 mg kg-1 each. Elevation of methaemoglobin was found only in the diflubenzuron- and triflumuron treated groups. The number of reticulocytes was increased in all of the treated groups. PMID- 8440877 TI - Effect of propane-1,2-diol ingestion on carbohydrate metabolism in female rat erythrocytes. AB - This study was undertaken to assess the effect of propane-1,2-diol(PD) ingestion on carbohydrate metabolism in female rat erythrocytes. For this purpose, two different groups of adult albino female rats were treated orally with PD at two different dose levels of 73 and 294 mg 100 g-1 body wt. The blood samples drawn from the retro-orbital sinus prior to the treatment served as the controls, whereas the treated samples were collected at peak periods (1/2 and 2 h) 2 and 7 days after the treatment. A single dose of PD was found to elevate levels of blood glucose, lactate, pyruvate and the lactate/pyruvate ratio at the peak periods (P < 0.001) and after 2 days (P < 0.001) in both the groups. A significant (P < 0.05) increase in the contents of erythrocyte 2,3 diphosphoglycerate (2,3-DPG) was observed only at the peak periods. All these parameters returned to their base level after 7 days of treatment. The activities of hexokinase (HK), 2,3-diphosphoglycerate phosphatase (2,3-DPG Pase), lactate dehydrogenase (LDH), glucose-6-phosphate dehydrogenase (G-6-PD), 6 phosphogluconate dehydrogenase (6-PGD) and aldehyde reductase II (AR II) declined markedly, whereas those of pyruvate kinase (PK) and aldose reductase increased as a result of PD ingestion. The changes in the activities of 2,3-DPG Pase and LDH were persistent up to 8 days post-treatment. The [14C]glucose flux through glycolysis and the hexose monophosphate shunt pathway in erythrocytes was found to be lowered (P < 0.001) in response to PD treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8440878 TI - Ethical considerations in the use of subliminal stimulation to improve handwashing compliance: scientific utility versus autonomy of the individual. PMID- 8440879 TI - Bacteriological side effects of gut decontamination with polymyxin E, gentamicin, and amphotericin B. PMID- 8440880 TI - Chemical disinfection of medical waste--a totally wrong approach. PMID- 8440881 TI - Mycobacterium tuberculosis transmission in healthcare settings: is it influenced by coinfection with human immunodeficiency virus? PMID- 8440882 TI - Transmission of HIV-associated tuberculosis to healthcare workers. AB - OBJECTIVE: A retrospective investigation was made to compare the occupational risk of tuberculosis in personnel assisting human immunodeficiency virus (HIV) infected and uninfected subjects with active tuberculosis. DESIGN: We retrospectively reviewed 6 years of hospital activity in 3 units where HIV infected patients with tuberculosis are hospitalized and in 2 units where non-HIV infected tuberculosis patients are hospitalized. The risk of occupational tuberculosis in healthcare workers who assisted HIV-infected and non-HIV-infected patients with tuberculosis was investigated. PARTICIPANTS: The risk of occupational tuberculosis in healthcare workers was studied by considering the numbers of potential source cases (hospitalized patients with tuberculosis) in the two conditions investigated (HIV-positive and HIV-negative). Both potential source cases and cases of tuberculosis in healthcare workers had to be microbiologically proven in order to be considered. RESULTS: Seven cases of tuberculosis occurred in persons who cared for 85 HIV-infected subjects with tuberculosis, while only 2 cases occurred in staff members who took care of 1,079 HIV-negative tuberculosis patients over the same period (relative risk = 44.4; 95% confidence interval = 8.5-438). CONCLUSIONS: Tuberculosis seems no longer to be a neglectable risk in healthcare workers assisting patients with HIV infection. Further study is urgently needed to see whether such unexpectedly high dissemination of tuberculosis also is demonstrable in the community. PMID- 8440883 TI - Nosocomial infections in surgical patients in the United States, January 1986 June 1992. National Nosocomial Infections Surveillance (NNIS) System. AB - OBJECTIVES: To describe the distribution of nosocomial infections among surgical patients by site of infection for different types of operations, and to show how the risk of certain adverse outcomes associated with nosocomial infection varied by site, type of operation, and exposure to specific medical devices. DESIGN: Surveillance of surgical patients during January 1986-June 1992 using standard definitions and protocols for both comprehensive (all sites, all operations) and targeted (all sites, selected operations) infection detection. SETTING AND PATIENTS: Acute care US hospitals participating in the National Nosocomial Infection Surveillance (NNIS) System: 42,509 patients with 52,388 infections from 95 hospitals using comprehensive surveillance protocols and an additional 5,659 patients with 6,963 infections from 11 more hospitals using a targeted protocol. RESULTS: Surgical site infection was the most common nosocomial infection site (37%) when data were reported by hospitals using the comprehensive protocols. When infections reported from both types of protocols were stratified by type of operation, other sites were most frequent following certain operations (e.g., urinary tract infection after joint prosthesis surgery [52%]). Among the infected surgical patients who died, the probability that an infection was related to the patient's death varied significantly with the site of infection, from 22% for urinary tract infection to 89% for organ/space surgical site infection, but was independent of the type of operation performed. The probability of developing a secondary bloodstream infection also varied significantly with the primary site of infection, from 3.1% for incisional surgical site infection to 9.5% for organ/space surgical site infection (p < .001). For all infections except pneumonia, the risk of developing a secondary bloodstream infection also varied significantly with the type of operation performed (p < .001) and was generally highest for cardiac surgery and lowest for abdominal hysterectomy. Surgical patients who developed ventilator-associated pneumonia were more than twice as likely to develop a secondary bloodstream infection as nonventilated pneumonia patients (8.1% versus 3.3%, p < .001). CONCLUSIONS: For surgical patients with nosocomial infection, the distribution of nosocomial infections by site varies by type of operation, the frequency with which nosocomial infections contribute to patient mortality varies by site of infection but not by type of operation, and the risk of developing a secondary bloodstream infection varies by type of primary infection and, except for pneumonia, by type of operation. PMID- 8440884 TI - Secondary measles vaccine failure in healthcare workers exposed to infected patients. AB - OBJECTIVE: To describe 4 healthcare workers who developed measles despite pre existing antimeasles antibody levels. DESIGN: Hospital employees working in patient care areas from July through November 1990 were screened for measles antibody levels using a commercially available enzyme immunoassay (EIA). The clinical course and laboratory evaluation of the 4 healthcare workers who developed measles were reviewed. SETTING: An academic tertiary care children's hospital. PARTICIPANTS: A convenience sample of resident physicians, nurses, ward clerks, Child Life workers, physical and occupational therapists, radiology technicians, and housekeeping staff were screened regardless of age, immunization status, or history of measles infection. RESULTS: Of 1,311 employees working in patient care areas, 900 (68.6%) had sera tested for measles antibody. Fourteen (1.5%) were negative, 338 (37.6%) had low positive antibody levels, 372 (41.3%) were mid-positive, and 171 (19%) were high-positive; 5 (0.6%) showed equivocal results. Four healthcare workers vaccinated in the past developed measles. All had positive pre-illness measles antibody levels and all had a significant rise in measles-specific IgG following infection. Three of the them had received at least 2 live measles vaccinations prior to caring for patients with measles. CONCLUSIONS: These cases raise concerns regarding detection of adequate protective measles immunity. We recommend that all healthcare workers observe respiratory precautions in caring for patients with measles. PMID- 8440885 TI - An outbreak of acute nonbacterial gastroenteritis in a nursing home. AB - OBJECTIVE: To determine risk factors for and modes of transmission of an outbreak of acute nonbacterial gastroenteritis among residents and staff in a nursing home. DESIGN: Cohort study of residents and questionnaire survey of employees. SETTING: One hundred twenty-bed nursing home in Alabama. PATIENTS: From July 11, 1991, through July 25, 1991, 77 of 120 residents (attack rate = 64%) and at least 14 of 49 employees (minimum attack rate = 29%) developed acute gastroenteritis characterized by vomiting and diarrhea; few residents developed fever > 100 degrees F. Nine residents required intravenous rehydration, and 2 residents died. RESULTS: The risk of developing illness was greater for female residents (64/92 versus 13/28; relative risk [RR] = 1.5; 95% confidence interval [CI95] = 1.0-2.3) and for employees who reported handling residents' soiled linen, stools, or vomitus more frequently (> 5 times a shift versus < or = 5 times a shift: 7/13 versus 7/31; RR = 2.4; CI95 = 1.1-5.4). Direct transmission of infection, probably via person-to-person spread, sustained the outbreak. Temporal clustering analysis demonstrated that the risk of becoming ill 1 or 2 days after a roommate became ill was significantly greater than that of becoming ill at other times during the outbreak (RR = 2.2; CI95 = 1.3-3.8). No Salmonella or Shigella species, ova, or parasites were identified from 12 fecal specimens obtained from ill residents. CONCLUSIONS: Although stool and serum specimens were not available for viral studies, the clinical symptoms and incubation period were consistent with illness due to Norwalk-like viral agents. This outbreak emphasizes the severity of acute nonbacterial gastroenteritis among elderly and debilitated residents of nursing homes and the need for prompt use of enteric precautions in controlling outbreaks of gastroenteritis in these facilities. PMID- 8440886 TI - The affinity between continuous quality improvement and epidemic surveillance. AB - OBJECTIVE: To discuss the close affinity between the continuous quality improvement (CQI) concept of monitoring a process for the introduction of special causes and epidemic surveillance. DESIGN: A case study of a CQI tool for infection control epidemic surveillance. SETTING AND PATIENTS: A 668-bed acute care hospital with 5 intensive care units supporting heart, liver transplant, and trauma teams. The infection control department consists of 2.5 full-time employee nurse epidemiologists and a medical director who is an infectious disease specialist. RESULTS: The outbreak investigation illustrates principles of CQI and their relationship to epidemic surveillance through the use of applied statistical methods. CONCLUSIONS: The expanding role of hospital epidemiology is enhanced by applying CQI concepts to improving health care. The application of epidemiologic tools and principles to the problems of nosocomial infections is strongly connected to the CQI concept of using dependable data to improve processes. PMID- 8440887 TI - Antimicrobial prophylaxis in surgery: mechanisms, misconceptions, and mischief. PMID- 8440888 TI - Strong allelic selection in the course of brother x sister matings in mice. AB - A set of 36 recombinant congenic mouse strains, resulting from crosses between B10.D2 and DBA/2, was created. During the backcross phase, animals were selected for their sensitivity to the graft-versus-host reaction induced by a B10.D2 hematopoietic cell transplant after irradiation. The progress of inbreeding was followed throughout the brother x sister phase by determining the allelic form of 14 genetic markers. During the backcross phase, the mean selective value per generation and per marker for the heterozygous allelic combination was 2.81 (1 for the homozygous B10.D2). During the brother x sister phase, this value was 1.15 and 0.30 for the heterozygous and the DBA/2 homozygous combinations, respectively (1 for the homozygous B10.D2). The origin of this strong allelic disadvantage for the DBA/2 homozygote, in the face of countervailing selection, is discussed. These data strongly suggest coadaptation between alleles constituting the genome of the inbred strains of the laboratory mouse, resulting in strong counterselection of the alleles derived from one inbred strain when a small amount is spread over the genetic background of another inbred strain. PMID- 8440890 TI - Albinism in a Suffolk sheep. AB - This report introduces the second form of true albinism to be documented in sheep, which appears mild enough not to cause serious undesirable side effects yet apparently effective enough to have the potential for general usage in the sheep industry. Based on the matings conducted to date, the albinism is inherited like an autosomal recessive. Histochemical tests reveal a defective melanin synthesis involving a block to the conversion of tyrosine to dopa but not the subsequent reactions that lead to melanin. The enzyme tyrosinase is a product of the C locus and catalyzes the conversion of tyrosine to dopa and the following reaction (dopa to dopaquinone). Therefore, it is proposed that the albinism arises from a gene in the C locus that encodes a defective tyrosinase. The gene is provisionally named albino marrabel, the gene symbol is cmar, and the locus allele symbol is Ccmar. PMID- 8440889 TI - Chromosomal analysis of D. melanogaster long-term selected lines. AB - Crosses and chromosomal substitutions among five selected lines of Drosophila melanogaster were carried out. These lines came from the same natural population after long-term selection for increasing dorsocentral bristle number. Two of them (Ac-27S and Ac-27P) show a bristle number around 16, and the other three (S-27S, S-27P, and N-21) present very extreme phenotypes, between 35 and 40 bristles. Selected genes were located on the three major chromosomes. Recessivity and synergistic interactions among the selected chromosomes account for the existence of hidden genetic variability, which can be released by selection, for a trait that scarcely shows phenotypic variability in populations. Genes responsible for selection response in lines Ac-27S and Ac-27P are present in all the selected lines, while lines S-27S, S-27P, and N-21 have accumulated additional increasing alleles common to the three of them. Long-term response and the extreme phenotypes achieved by these three lines point to variation that arose de novo during the selection process. However, this idea disagrees with the low genetic variability found between them. All these facts are consistent with the idea that variability originated in the course of selection by a low-probability nonrandom mechanism such as the occurrence of rare recombination events. PMID- 8440891 TI - A potential role for superantigens in the pathogenesis of psoriasis. AB - Psoriasis is a complex inflammatory skin disease in which local vascular changes, T-cell activation, abnormal keratinocyte proliferation and differentiation, and neutrophil activation all contribute to the ongoing disease process. Because of recent interest in T-cell activation as a trigger for psoriatic lesions, we hypothesized that psoriasis may be triggered by superantigens, e.g., toxins of microbial origin that stimulate T cells expressing particular T-cell receptor (TCR) beta chain variable (V beta) gene segments. Lesional skin biopsies and peripheral blood from two patients with acute exacerbations of their psoriasis that appeared to be triggered by infection were analyzed for TCR V beta gene expression using monoclonal antibodies directed against V beta 5.1, 5.2, 6.7, 8.1, and 12. Skin biopsies from both patients demonstrated a different pattern of V beta expansion that correspond to the V beta pattern expected to be induced by the type of superantigen expressed during the infection. In contrast, using immunofluorescence and flow cytometry, peripheral blood T cells from these patients did not demonstrate any expansion of the 5 V beta subsets studied. These observations support the hypothesis that local activation of cutaneous T cells in psoriasis may be caused by a superantigen and provides a new direction for investigating the pathogenesis of this complex and fascinating skin disorder. PMID- 8440892 TI - Reconstitution of hair follicle development in vivo: determination of follicle formation, hair growth, and hair quality by dermal cells. AB - Combinations of cultured and uncultured epidermal and dermal cell preparations from newborn and perinatal mice were grafted onto the backs of athymic nude mouse hosts to elucidate the cellular requirements for skin appendage formation. All epidermal populations studied, including a total epidermal keratinocyte preparation from trypsin-split skin, developing hair follicle buds isolated from epidermis, and preformed hair follicles isolated from dermis, make haired skin when grafted with fresh dermal cells. Only pre-formed hair follicles produce haired skin on grafts without an additional dermal component. Hair follicle buds grafted alone or with cultured dermal cells will reconstitute skin but without appendage formation. Thus, cells or factors present in fresh, but not cultured, dermal cells are essential for supporting hair growth from budding follicles, whereas more developed (pre-formed) follicles appear to contain all the necessary components for hair formation. Dissociation of isolated hair follicles by trypsin/ethylenediaminetetraacetic acid prior to grafting is permissive for hair growth, suggesting that follicle cells can be re-induced or reassociate in vivo. Dermal papilla cells, microdissected from rat vibrissal follicles and cultured for up to 14 passages, stimulate hair growth from follicle buds and influence the quality of hair growth from pre-formed hair follicles. Thus, dermal papilla cells maintain inductive capacity in culture and contribute to the reconstituted skin. This reconstitution model should be useful for identifying cell populations within the hair follicle compartment necessary for hair growth and for examining the effects of specific gene products on hair follicle growth and development in vivo. PMID- 8440893 TI - Cyclosporin A prolongs human hair growth in vitro. AB - We studied the effect of cyclosporin A on human hair growth using a recently described model in which isolated hair follicles are grown in vitro. Cyclosporin A had no effect on the rate of hair growth, but at 10(-7) M, a dose within the therapeutic blood range, it maintained hair growth for longer than control to give a 42% greater mean follicle elongation after 15 d (p < 0.05). Eighteen of 42 cyclosporin-treated follicles (43%) were still growing after 15 d compared with one of 42 control follicles (2%). These results suggest that the hypertrichotic action of cyclosporin A may be due to prolongation of the anagen phase of the hair-growth cycle. PMID- 8440894 TI - Effects of the selective protein kinase C inhibitor, Ro 31-7549, on the proliferation of cultured mouse epidermal keratinocytes. AB - We have investigated the effects of Ro 31-7549, a selective protein kinase C (PKC) inhibitor, on DNA synthesis and proliferation in two primary mouse epidermal keratinocyte culture systems. In differentiating keratinocytes incubated in medium containing 10% serum and high calcium (approximately 0.5 mM), Ro 31-7549 blocked the inhibitory effect of the phorbol ester 12-0-tetradecanoyl 13-acetate (TPA) (a PKC activator) on keratinocyte DNA synthesis at 24 h [50% maximal response concentration (EC50) = 1 microM], consistent with inhibition of PKC-mediated differentiation. Continuous treatment of the differentiative culture system with the PKC inhibitor resulted in a marked (fourfold) stimulation of [3H]thymidine incorporation at day 7 of exposure, with an EC50 of 0.25 microM. The potencies of these effects of Ro 31-7549 are comparable to that reported for inhibition of TPA-induced platelet 47-kD protein phosphorylation [50% inhibitory concentration (IC50) = 4.4 microM]. The time course of [3H]thymidine incorporation indicated that Ro 31-7549 did not directly stimulate DNA synthesis but instead prevented the loss of proliferative capacity associated with continued culture in this medium. Maximal stimulation (2.6 times) of DNA synthesis was observed on day 4, whereas DNA synthesis at day 1 was unaffected. In a highly proliferative culture system using serum-free medium containing 25 microM calcium, TPA dose-dependently inhibited proliferation with an IC50 of approximately 0.3 mM. This antiproliferative effect of TPA was largely reversed by 0.1 microM Ro 31-7549. In the proliferative culture system, 0.75 microM Ro 31 7549 also essentially reversed the inhibition of proliferation caused by switching to high (1.0 mM) calcium. These results suggest that the loss of proliferative capacity in differentiating epidermal keratinocyte cultures may be mediated, at least in part, by PKC. PMID- 8440895 TI - Wallace H. Clark, Jr., M.D.: a biography and annotated bibliography. PMID- 8440896 TI - Wallace Clark Festschrift on Melanoma. PMID- 8440897 TI - Is carcinogenesis fundamentally adversarial-confrontational or physiologic adaptive? AB - The dominant dogma concerning the essential cellular changes during preneoplasia and precancer considers these as abnormal or foreign that evoke a basic "host parasite" response. An alternative view of how cancer develops, here briefly outlined, views the early and intermediate cellular changes as essentially physiologic and adaptive. This different concept introduces clonal adaptation as a basic response to many genotoxic carcinogenic stimuli including chemicals, radiations, and some viruses. The evidence in support of this new view of the carcinogenic process is summarized. PMID- 8440898 TI - Analysis of the protective effect of different sunscreens on ultraviolet radiation-induced local and systemic suppression of contact hypersensitivity and inflammatory responses in mice. AB - We investigated the capacity of three sunscreen compounds to protect mice from the inflammatory and immunosuppressive effects of ultraviolet radiation (UVR). The sunscreen preparations contained 7.5% 2-ethylhexyl-p-methoxycinnamate, 8% octyl-N-dimethyl-p-aminobenzoate, or 6% benzophenone-3 in an oil-in-water emulsion. Skin swelling was used as the measure of their effect on UVR-induced inflammation, and immunosuppression was assessed by contact sensitization with 2,4-dinitrofluorobenzene applied to UV-irradiated skin (local suppression) or a distant site (systemic suppression). The sunscreens were applied to the shaved dorsal skin of C3H mice, which were then given a single dose of UVR ranging from 2 to 32 kJ/m2 within the UVB (280-320 nm) region. All three sunscreens gave complete protection against local suppression of contact hypersensitivity caused by a dose of 2 kJ/m2 UVB. They also protected against both inflammation and systemic immunosuppression caused by UVR; however, protection was highly dependent on the UVR dose. Furthermore, the sunscreens were less effective in protecting against systemic immunosuppression than against inflammation. These results indicate that immunosuppression is less sensitive to the protective effects of the sunscreens than inflammation and that protection against UVR induced inflammation does not necessarily imply prevention of immunologic alterations. In addition, these studies suggest that UVR-induced immunosuppression and inflammation may involve different mechanisms. PMID- 8440899 TI - Cytogenetics of melanocytic tumors. AB - Chromosome studies of human melanocytic tumors have demonstrated non-random karyotypic abnormalities of chromosomes 1, 6, 7, 9, and 10. These visible genetic alterations may provide clues to the location of oncogenes and suppressor genes involved in the development of lesions from benign nervus to metastatic melanoma, and to the mechanisms by which the function of these genes is altered. To date, however, none of the specific growth regulatory genes important in this neoplastic progression has been identified, with the possible exception of the erbB oncogene in the later stages. Recent results in other human tumors do suggest, however, that the combined cytogenetic and molecular genetic approach will soon lead to the recognition of a number of important genes, both inherited and somatically altered, and that significant clinical applications will follow. PMID- 8440900 TI - Melanin pigments and melanosomal proteins as differentiation markers unique to normal and neoplastic melanocytes. AB - This report introduces some aspects of our current basic research focus on the unique metabolic pathways within the melanocyte. Using this approach, we hope to gain a better understanding of the pathophysiology of malignant melanoma and develop early laboratory diagnostic tests for this disease. Specifically, we will discuss that: 1) the synthesis of pheomelanin is markedly increased in malignant melanoma and dysplastic melanocytic nevi; 2) high levels of metabolites of pheomelanin and eumelanin can be detected in the urine and blood of patients with metastatic melanoma; 3) this release of melanin metabolites appears to correlate with tumor thickness and tumor load, including the extent of metastasis; 4) the synthesis of melanosomal proteins also becomes aberrant in malignant melanoma; and 5) this abnormal melanosome synthesis can be utilized in the identification of antigenic epitopes that are uniquely expressed in malignant melanoma. We believe that this synthesis and secretion of abnormal melanin pigment and melanosomal proteins (human melanosome-specific antigen) would be useful for the development of early laboratory diagnostic and monitoring tools for malignant melanoma. In addition, we also report the detection of pheomelanin component in "normal" unexposed skin; however, the relative amount of pheomelanin in the skin does not reflect hair color (e.g., red hair). The nature of this pheomelanin component in the skin needs to be further clarified. PMID- 8440901 TI - Antioxidant defense mechanisms in murine epidermis and dermis and their responses to ultraviolet light. AB - A comprehensive comparison of antioxidant defenses in the dermis and epidermis and their response to exposure to ultraviolet (UV) irradiation has not previously been attempted. In this study, enzymic and non-enzymic antioxidants in epidermis and dermis of hairless mice were compared. Enzyme activities are presented both as units/gram of skin and units/milligram of protein; arguments are presented for the superiority of skin wet weight as a reference base. Catalase, glutathione peroxidase, and glutathione reductase (units/gram of skin) were higher in epidermis than dermis by 49%, 86%, and 74%, respectively. Superoxide dismutase did not follow this pattern. Lipophilic antioxidants (alpha-tocopherol, ubiquinol 9, and ubiquinone 9) and hydrophilic antioxidants (ascorbic acid, dehydroascorbic acid, and glutathione) were 24-95% higher in epidermis than in dermis. In contrast, oxidized glutathione was 60% lower in epidermis than in dermis. Mice were irradiated with solar light to examine the response of these cutaneous layers to UV irradiation. After irradiation with 25 J/cm2 (UVA + UVB, from a solar simulator), 10 times the minimum erythemal dose, epidermal and dermal catalase and superoxide dismutase activities were greatly decreased. alpha Tocopherol, ubiquinol 9, ubiquinone 9, ascorbic acid, dehydroascorbic acid, and reduced glutathione decreased in both epidermis and dermis by 26-93%. Oxidized glutathione showed a slight, non-significant increase. Because the reduction in total ascorbate and catalase was much more severe in epidermis than dermis, it can be concluded that UV light is more damaging to the antioxidant defenses in the epidermis than in the dermis. PMID- 8440902 TI - Pyridoxine toxicity to cultured fibroblasts caused by near-ultraviolet light. AB - Pyridoxine, like riboflavin, has absorption in the range of near ultraviolet (UVA; 320-400 nm) radiation and is known to decompose after long irradiation with germicidal lamps. Thus, the possibility of UVA-induced pyridoxine photosensitization was studied in cultured normal human, hydroa vacciniforme, and xeroderma pigmentosum fibroblasts. Cytotoxicity caused by the sensitization was measured by post-UVA colony formation. Pyridoxine showed strong cytotoxic effect after UVA radiation and the effect remained for at least 60 min after UVA radiation. Although the cytotoxicity decreased a little when pyridoxine was irradiated under anaerobic conditions, the amount of hydrogen peroxide produced by UVA radiation was hardly cytotoxic and the rate of photodecomposition of pyridoxine was slower under anaerobic conditions than aerobic ones. Thus, the toxicity seemed to depend mostly on the photoproducts of pyridoxine. The UVA induced pyridoxine cytotoxicity was not due to DNA damage that is to be excision repaired because group A and C xeroderma pigmentosum fibroblasts were killed as in the case of normal human fibroblasts. PMID- 8440903 TI - Non-melanosomal regulatory factors in melanogenesis. AB - The enzyme activity of tyrosinase, catalase, and peroxidase and the number of metal ions in melanogenic subcellular compartments in pigment cells were measured. Coated vesicles were richest in tyrosinase and catalase, whereas premelanosomes had the highest amount of peroxidase. Among metals ions examined, copper, zinc, and iron were more concentrated in pre-melanosomes than in coated vesicles. A quantitative analysis revealed that peroxidase served to enhance eumelanin polymer formation from monomers in the presence of hydrogen peroxide and metal ions, especially copper ions, which had the greatest enhancing effect on the conversion of monomers to polymers. PMID- 8440904 TI - Growth regulation of cultured human nevus cells. AB - Cells isolated from congenital melanocytic nevi and cultured in vitro have growth characteristics that resemble their premalignant stage in situ. A serum-free, chemically defined medium has been developed that allows continuous growth of established nevus cultures for up to several months. Like primary melanoma cells, nevus cells in high-calcium-containing W489 medium require insulin for growth. In contrast to melanoma cells, nevus cells in serum-free medium require the presence of alpha-melanocyte-stimulating hormone, which enhanced intracellular levels of cyclic adenosine monophosphate. In contrast to the requirements of normal human melanocytes from newborn foreskin, congenital nevus cells grow with less dependency on basic fibroblast growth factor (bFGF). Nevus cultures contain bFGF like activity, and they express bFGF mRNA. Nevic cells of compound nevi also express bFGF mRNA in situ but only in the junctional areas. These results indicate that bFGF plays an important growth regulatory role for nevus cells in vitro and in vivo. PMID- 8440905 TI - Epidermal Langerhans cells are resistant to the permeabilizing effects of extracellular ATP: in vitro evidence supporting a protective role of membrane ATPase. AB - Extracellular adenosine 5'-triphosphate (ATPo) can induce pore formation in cell membranes, leading to cell permeabilization and eventual cell death. In this study, we examined the sensitivity of human epidermal Langerhans cells to ATP induced permeabilization and tested the possibility that the Mg(++)- or Ca(++) dependent plasma membrane ectonucleotidase (mATPase) on Langerhans cells provides protection against the cytotoxic effects of ATPo. Membrane permeability was assessed by using the fluorescent tracer propidium iodide, which confers red nuclear fluorescence to permeabilized cells. Langerhans cells were identified within human epidermal cell suspensions with fluorescein isothiocyanate conjugated MoAb against CD1a or human leukocyte antigen-DR (HLA-DR) antigens. Cultured human keratinocytes and J774 macrophages were both highly sensitive to permeabilization induced by incubation with ATP (0.5 to 20 mM at 37 degrees C), whereas Langerhans cells were relatively resistant. The non-hydrolyzable ATP analog, adenosine 5'-(beta,gamma-imido) triphosphate, but not other nucleotides such as ADP, AMP, GTP, or UTP, was also able to induce permeabilization comparable to that of ATP, thereby suggesting that ATP hydrolysis is not required for this effect. ATP4- is the moiety most likely responsible for permeabilization, because propidium iodide uptake occurred only when the pH of the medium was > or = 7.4. Permeabilization induced by ATP was augmented by chelation of divalent cations with ethylene-diamine-tetraacetic acid and by the addition of lanthanum or cerium (0.01 to 1 mM). Finally, incubation with the adenosine analog, 5'-p-fluorosulfonylbenzoyl-adenosine (1 mM), inhibited mATPase staining of Langerhans cells in human epidermal sheets, but markedly augmented ATP-induced permeabilization of Langerhans cells. The results indicate that epidermal LC are resistant to the lytic effects of ATPo and that mATPase is involved in such resistance. PMID- 8440906 TI - Interferon gamma regulation of de novo protein synthesis in human dermal fibroblasts in culture is anatomic site dependent. AB - The propensity of the skin of the lower anterior leg to be involved in Graves' dermopathy prompted an examination of the specific protein synthesis and response to interferon gamma in cultured fibroblasts from this area. Confluent cultures from normal skin of the lower leg and from the abdomen of the same three donors were pulse labeled with [35S]methionine for 3 h and subjected to two-dimensional protein gel electrophoresis and fluorography. Protein spots were mapped using a computer-driven program and the relative densities of the resolvable spots analyzed. Fibroblasts from the two anatomic sites display distinct patterns of de novo protein synthesis. Of the 157 abundant spots arbitrarily chosen for analysis, 31% varied substantially in levels of expression between the sites. A number of proteins appear to be expressed only in cultures derived from one of the two anatomic sites. Interferon gamma (100 U/ml) present in the culture medium for 48 h influenced the abundance of a number of proteins in a site-specific manner. Among them, plasminogen activator inhibitor type-1 was induced three to five times in the leg cultures, whereas this same polypeptide was down-regulated in abdominal fibroblasts. A 54-kD protein was induced in interferon-treated cultures from both sites at least 50 times. It appears that fibroblasts from different regions of the integument are intrinsically distinct in terms of both their protein synthetic programs and their responses to cytokines. PMID- 8440907 TI - Hair follicles, stem cells, and skin cancer. PMID- 8440908 TI - Eccrine differentiation in basal cell carcinoma. AB - Eccrine differentiation according to histologic and immunohistochemical criteria was demonstrated in 16 of 66 basal cell carcinomas. The possibility of origin of these neoplasms from the eccrine duct, including the acrosyringium, is discussed in relation to the differences in site distribution and etiology between basal cell carcinoma and squamous cell carcinoma. PMID- 8440909 TI - Increased interleukin 6 production by T cells derived from patients with atopic dermatitis. AB - Many immunologic aspects of atopic dermatitis have been studied, but basic pathobiologic mechanisms of this disease remain unknown. In this study, we measured the production of interleukin-6 (IL-6) by peripheral blood T cells and monocytes from patients with atopic dermatitis in comparison to normal control subjects and patients with chronic psoriasis. We found that peripheral blood T cells isolated from patients with atopic dermatitis produced significantly higher levels of IL-6 (36.1 +/- 5.1 units/ml, n = 22) than T cells derived from either normal subjects (12.6 +/- 1.9 units/ml, n = 22) or patients with chronic psoriasis (26.7 +/- 4.1 units/ml, n = 7). T-cell activation was also measured in the patients with atopic dermatitis by soluble serum IL-2 receptor levels and were found to be significantly higher (623.7 +/- 8.1 units/ml, n = 8) than normal subjects (357.2 +/- 26.0 units/ml, n = 8). In contrast to the increased production of IL-6 by T cells in atopic dermatitis, there was no significant difference in the IL-6 production by peripheral blood monocytes derived from patients with atopic dermatitis compared to normal subjects. Thus, peripheral blood T cells derived from patients with AD spontaneously produce increased amounts of IL-6 compared to T cells from normal subjects, which may reflect the increased activation state of T cells in atopic dermatitis. These data support the concept that activated T cells or subsets of T cells may be important effector cells in mediating inflammatory activity in atopic disease. PMID- 8440910 TI - Giant congenital nevi: a conceptualization of patterns. AB - Patterns in giant congenital nevi are classified as to extent of cellular involvement of the reticular dermis and by the quality of the fibrous matrix. In addition, classifications are influenced by degrees of cellular atypia. Two general categories are defined. In one, the phenomena are relatively independent of those operative at the dermal-epidermal interface. The lesions are characterized as dermal congenital tumorous dysplasias-blastomas. They are subdivided into major, intermediate, and minor categories and into mature and immature variants. In these variants, disparate populations in the patterns of nodules and plaques (lumpy-bumpy variants) qualify as dermal variants of minimal deviation melanoma as seen in the setting of giant congenital nevi. The respective melanomas in this category are small-cell malignant neoplasms (melanoblastomas of infancy and childhood). In a second category in the clinical setting of giant congenital nevus, rare childhood and some adult melanomas of a more common histologic type evolve from lentiginous and junctional components in patterns that recapitulate those of the dysplastic nevus syndrome. The suspicious areas in all categories are evaluated by the same clinical criteria. In the dysplasia-blastoma category, enlarging nodules must be biopsied. The criteria for the evaluation of lesions in the dysplastic nevus syndrome and in the category of minimal deviation melanoma have application to the unstable regions in giant congenital nevi. PMID- 8440911 TI - Immunophenotyping of compound and spitz nevi and vertical growth-phase melanomas using a panel of monoclonal antibodies reactive in paraffin sections. PMID- 8440912 TI - Penetration of autoantibodies into living epithelial cells. AB - The ability of autoantibodies to penetrate living cells is controversial. We have identified immunoglobulin G (IgG) antibodies capable of penetrating an epithelial cell line, COLO-16, in five of 36 (14%) antinuclear antibody positive sera from patients with SLE. Thirty minutes following incubation of cells with dilutions of either whole sera, globulin fractions, or F(ab')2 fragments of IgG, approximately 80-90% of cells demonstrated intranuclear IgG by indirect immunofluorescence. Viability of cells prior to assay was > 98% as determined by trypan blue staining and penetration of IgG into the nuclei did not affect viability or DNA synthesis of the cells in short-term culture. Intracellular IgG could not be detected following exposure of the cells to high-titer reference autoantibodies of known specificities (against DNA, Ro, La, Sm, RNP, or ribosomes). Furthermore, absorption of the sera with either DNA or chromatin failed to abolish intranuclear penetration, indicating that the autoantibodies were not directed against DNA receptors or nucleosomes on the cell surface. Antibody uptake was relatively selective for epithelial cell lines, because intranuclear IgG was not detected in cell lines of lymphoid origin exposed to the sera. Two of the five sera immunoprecipitated proteins of molecular weight 88 kD with or without a 68 kD protein from COLO-16 cells labeled with 125I at the cell surface. These findings indicate that a subset of SLE patients have IgG capable of penetrating a cell line of epithelial origin. These antibodies, most likely, bind to cell surface proteins and are translocated into the cell nucleus. Although direct immunofluorescence of a skin biopsy obtained from one of the five patients with "penetrating IgG" also showed intranuclear staining for IgG, the biologic relevance of these findings remains to be determined. PMID- 8440913 TI - Histopathologic recognition and grading of dysplastic melanocytic nevi: an interobserver agreement study. AB - Before the controversies surrounding dysplastic melanocytic nevi are resolved, dermatopathologists must be able to reliably distinguish dysplastic nevi from common acquired nevi and malignant melanoma. To establish whether grading of melanocytic dysplasia has any biologic relevance, dermatopathologists must be able to consistently recognize two or more grades of atypia. We studied the concordance among five dermatopathologists for recognition and grading of 60 nevomelanocytic lesions. Ten cases from each of the following categories of melanocytic proliferation were retrieved from the Massachusetts General Hospital files: 1) common melanocytic nevi, 2) melanocytic nevi with features of dysplastic nevi, 3) dysplastic nevi with slight cytologic atypia, 4) dysplastic nevi with moderate cytologic atypia, 5) dysplastic nevi with severe cytologic atypia, and 6) primary malignant melanoma. The slides were reviewed independently; no discussion of diagnostic criteria preceded the review. Overall concordance for diagnosing dysplastic nevi was 77%, with a kappa statistic of 0.55-0.84. Furthermore, in grading dysplastic nevi, experienced dermatopathologists had a concordance ranging from 35% to 58% (kappa value 0.38 0.47). Those with less experience in grading dysplastic nevi had a concordance of 16-65% (kappa value 0.05-0.24). The five observers in this study reliably distinguished dysplastic nevi from common acquired nevi and malignant melanoma. Further refinement of the criteria for grading of nevo-melanocytic dysplasia and experience in grading are critical for accuracy in subcategorization of dysplastic nevi. Consistent, reproducible subcategorization of dysplastic nevi is a requisite before the issue of biologic or prognostic relevance of grading (dysplastic nevi) can be addressed. This study supports the validity of existing criteria for the diagnosis of dysplastic nevi because the problems in diagnosis were at the limits of the spectrum, namely, discrimination of slightly atypical dysplastic nevi from common nevi and severely atypical dysplastic nevi from radial growth phase melanoma. PMID- 8440914 TI - Melanocytic nevi in histologic association with primary cutaneous melanoma of superficial spreading and nodular types: effect of tumor thickness. AB - The histologic presence of benign dermal nevus cells in contiguity with primary cutaneous melanoma, as a distinct population separate from malignant melanocytes, was evaluated in a large referral data base. The melanomas were limited to superficial spreading melanoma (SSM) and nodular melanoma (NM). Overall, dermal melanocytic nevi were found associated with 1126 of 1954 primary SSM/NM (57.6%). When the melanomas were stratified by tumor thickness, an inverse relationship between the presence of benign nevus cells and tumor thickness was found: 64.9% of tumors less than 0.76 mm and 64.5% of those between 0.76 and 1.69 mm were associated with dermal nevi, whereas in the thickness range 1.70-3.60 mm, there were 45.6% associated nevi, and in melanomas greater than 3.60 mm, there were only 32.0% noted to have nevus cells. When melanomas were separated by nevus type, it was found that 41% were associated with an acquired pattern nevus, 38% with congenital pattern nevus, and 21% with dysplastic nevus. It may be concluded that 1) the histologic presence of nevus cells is a common event in SSM/NM; 2) the association of melanocytic nevus and melanoma is more easily demonstrated in thinner tumors; and 3) acquired pattern nevi, congenital pattern nevi, and dysplastic nevi are all potential precursors of melanoma. PMID- 8440915 TI - Expression of functional alpha 4 beta 1 integrin by human dermal fibroblasts. AB - Fibroblasts interact with the extracellular matrix through cell-surface receptors belonging to the integrin family. In this report, we present evidence that cultured normal human fibroblasts express the integrin alpha 4 beta 1 and that this receptor facilitates fibroblast attachment to fibronectin. Fluorescence activated cell sorter analysis and immunoprecipitation with monoclonal antibodies demonstrated that normal dermal fibroblasts express the alpha 4-subunit on the cell surface, primarily in association with the beta 1-subunit. Cell-attachment assays demonstrated that normal human fibroblasts can attach to the 40-kDa fibronectin fragment containing the type III connecting segment domain recognized by alpha 4 beta 1. Adhesion to this fragment was inhibited by anti-alpha 4 antibody. Furthermore, our results indicate that alpha 4 beta 1 collaborates with another fibronectin receptor, alpha 5 beta 1, during fibroblast attachment to full-length fibronectin. The region of fibronectin recognized by alpha 5 beta 1 contains the amino acid sequence arg-gly-asp (RGD). A short synthetic RGD peptide, or the 120-kDa fibronectin fragment containing the RGD sequence, only partially inhibited attachment to full-length fibronectin, suggesting that fibroblasts utilize more than the RGD recognition sequence for binding to fibronectin. Accordingly, RGD peptide combined with anti-alpha 4 antibody produced more potent inhibition of cell attachment than either reagent alone. These observations show for the first time that functional alpha 4 beta 1 fibronectin receptor is not restricted to lymphoid cells and transformed cells. PMID- 8440916 TI - Tumor progression in ocular melanomas. AB - The term ocular melanoma refers to a heterogeneous group of cancers of melanocytic origin. The precursor of most cases of conjunctival melanoma is known to ophthalmologists as primary acquired melanosis. This condition passes through well-defined stages of tumor progression. Although tumor progression is not obligatory, as a conjunctival melanocytic lesion acquires new biologic properties it is more likely to progress further. Although junctional nevi are seldom encountered beyond childhood and primary acquired melanosis usually develops in middle-aged individuals, these two conditions may be histologically indistinguishable. Most junctional nevi eventually show evidence of differentiation, whereas nearly half of the cases of primary acquired melanosis with atypia progress to melanoma. Therefore, it is possible that aging may modulate the capability of certain clonal proliferations to differentiate. Uveal melanocytes normally reside in mesenchyme, so that the traditional histologic criterion for establishing the diagnosis of most melanomas--breach of an epithelial basement membrane--does not apply. Because uveal melanomas are not easily accessible to incisional biopsy (without disruption of vision), only two points in the spectrum of tumor progression are defined clinically: nevus and melanoma. Experimental evidence suggests that a spectrum of atypical melanocytic proliferations separates benign nevi from melanomas capable of generating metastases. Unlike conjunctival melanomas that spread first to regional lymph nodes, choroidal and ciliary body melanomas preferentially spread first to the liver and are examples of organ-specific metastases. PMID- 8440917 TI - Expression of type VI collagen mRNA during wound healing. AB - During the highly regulated process of wound healing the expression of the interstitial collagens I and III is increased in a time-dependent fashion. Although ultrastructural and in vitro studies suggest a physiologic role of collagen VI in the organization of extracellular matrix deposition, nothing is known about its role in wound healing. Therefore, we studied collagen VI gene expression during wound healing in humans compared to that of collagens I and III. The presence of specific alpha 1(VI) and alpha 3(VI) mRNA species in scar tissue was demonstrated by Northern blot analysis. Quantification of mRNA expression by dot blot analysis and in situ hybridization indicated that like for the interstitial collagens I and III collagen VI gene expression was increased during wound healing, reaching its maximum 2 weeks after initial insult. In the late phase of wound healing like alpha 1(I) the alpha 1(VI) gene expression was not down regulated significantly. In contrast, a reduction of alpha 3(VI) collagen gene expression was observed, as was for the alpha 1(III) collagen gene, indicating a non-coordinate regulation of these chains. Collagen VI gene expression could be localized to fibroblast-like cells and to endothelial cells of newly formed vessels. Collagen VI gene expression was undetectable in smooth muscle cells and myoepithelial cells of eccrine glands. These results indicate that collagen VI gene expression is regulated in a time-dependent fashion and that fibroblasts and endothelial cells appear to play an important role in collagen VI synthesis during wound healing. PMID- 8440918 TI - Early detection of malignant melanoma: observation on results of educational strategies. PMID- 8440919 TI - Autologous melanoma vaccine induces inflammatory responses in melanoma metastases: relevance to immunologic regression and immunotherapy. AB - Human primary malignant melanoma is often accompanied by a host response of infiltrating lymphocytes suggestive of tumor antigen-induced immunity and correlated in some tumors with prognosis. Whereas metastatic melanoma deposits typically are not inflamed and contain relatively few lymphocytes and dendritic immune cells, immunization with autologous melanoma-cell vaccine may induce a clinical inflammatory response associated with mononuclear-cell infiltration. In this study, we characterize immune responses to dermal and subcutaneous melanoma metastases in dinitrophenyl (DNP)-pre-sensitized patients immunized with DNP conjugated melanoma cells. Patients so treated develop cutaneous delayed hypersensitivity responses to DNP-conjugated autologous mononuclear cells, and approximately one-half show clinical evidence of inflammation and regression of metastases within 2-4 months. Whereas pre-vaccination biopsies of metastatic melanoma failed to reveal significant infiltration by lymphocytes, biopsies obtained after vaccination and coincident with clinical inflammation were markedly infiltrated preponderantly by T cells with a CD8+ phenotype. Clustering of these cells about individual degenerating melanoma cells in a manner analogous to "satellitosis" was a consistent feature of this reaction. Enhanced expression of intercellular adhesion molecule-1 (ICAM-1) and human leukocyte antigen (HLA) DR by melanoma cells were invariably associated with zones of T-cell infiltration, whereas diminished or absent expression was observed in relatively unaffected regions of tumors. Numerous HLA-DR+, CD4+, CD1-, Leu-1- dendritic cells were also associated with zones of early T-cell infiltration. These data indicate that clinical inflammation and regression of metastatic melanoma induced by autologous melanoma-cell vaccine involves activated T cells with cytotoxic suppressor phenotype and dendritic cells putatively capable of local antigen presentation. ICAM-1 upregulation on melanoma cells is a likely mediator of ligand interaction between infiltrating T cells and target cells in this model of antigen-induced host anti-tumor response. Structural alterations identified in this setting (e.g., tumor cell satellitosis) may provide additional insight into identifying features of naturally occurring host immune responses to primary cutaneous melanomas. PMID- 8440920 TI - Lessons from tumor progression: the invasive radial growth phase of melanoma is common, incapable of metastasis, and indolent. AB - Primary melanoma generally evolves through three clinically and morphologically discernable tumor progression steps. Transformed melanocytes first proliferate above the epidermal basement membrane, then invade the papillary dermis (the in situ and invasive radial growth phases of melanoma), and subsequently develop the capacity to grow as a tumor (the vertical growth phase). Here, we address three aspects of the invasive radial growth phase that provide the rationale for viewing it as the critical lesion for melanoma detection and therapy. We determined the fraction of melanomas having this growth phase, tested its hypothesized incapacity to metastasize, and estimated its longevity. The high prevalence of this step in tumor progression was demonstrated in a data base of 624 patients, where at least 87% of melanomas exhibited a radial growth phase. The benignity of this lesion was evinced by the perfect metastasis-free survival of 161 patients treated for pure radial growth-phase melanomas and followed for a median of 13.7 years. Its indolence was evident in an analysis of the ages of 234 patients with superficial spreading melanomas without or with vertical growth phase: The cases with lesions having only radial growth phase were 4.3 years younger than those additionally having vertical growth phase (p < 0.05). These features of the invasive radial growth phase of primary melanoma, first described by Wallace H. Clark, make it a pivotal lesion in the evolutionary biology of melanocytic neoplasia and confirm its central place in public health programs to control melanoma mortality. PMID- 8440921 TI - Direct interaction of antifungal azole-derivatives with calmodulin: a possible mechanism for their therapeutic activity. AB - Azole derivatives, such as ketoconazole and bifonazole, are well-established antifungal drugs. Recently, these compounds have been reported to have therapeutic efficacy also in inflammatory skin disorders. There is increasing evidence that calmodulin is involved in fungal infections as well as in inflammatory skin diseases. Therefore, we investigated the effects of various antifungal drugs on calmodulin activity, using calmodulin-dependent phosphodiesterase as an indicator for the calmodulin activity. All azole derivatives tested competitively inhibited calmodulin activity with 50% inhibitory concentration values in the low micromolar range. In contrast, antifungal drugs belonging to other chemical classes did not display inhibitory activity. Thus, this study provides evidence that direct interaction with calmodulin might contribute to the therapeutic activity of azole derivatives, particularly to their efficacy in the treatment of inflammatory skin disorders. PMID- 8440922 TI - A cohort study of melanoma in patients with dysplastic nevi. AB - A historical cohort of 153 patients with dysplastic nevi was studied for the development of melanoma. Each subject had a minimum follow-up of 5 years, with an average study follow-up of 94 months. Eleven new melanomas developed in 11 patients between 11 and 143 months (average 61 months) into the study period. Age adjusted melanoma incidence in the cohort was 692/100,000 person years. Development of melanoma was strongly correlated with prior personal and/or family history of melanoma. Even among the 89 patients with no personal or family history of melanoma, the age-adjusted incidence of melanoma was an alarming 154/100,000 person years. Within this small, non-randomly ascertained cohort no association could be discerned between melanoma incidence and total number of banal or dysplastic nevi. These findings support the public health significance of the recognition of dysplastic nevi and confirm the importance of family history in evaluating melanoma risk associated with dysplastic nevi. PMID- 8440923 TI - Risk of melanoma and other cancers in melanoma-prone families. AB - We evaluated the risk of developing melanoma over time in members of 23 melanoma prone families. All 23 families had dysplastic nevi as well as melanoma. Forty seven melanomas occurred prospectively, all in family members with dysplastic nevi. The prospective melanomas were markedly thinner than the melanomas diagnosed prior to or at the time of the subject's entry into the study. The cumulative risk of melanoma by age 50 years among people with dysplastic nevi was 48.9% +/- 4.2%. Overall, the relative risk of a prospective melanoma among family members with previous melanoma was 229 (95% confidence interval 110-422). The risk varied by time interval and was 362 in the first 5 years, decreasing to 120 after 5 years. The risk of developing melanoma was 85 times increased (95% confidence interval 41-156) in family members with dysplastic nevi and also declined over time in this group. There was no significant excess of cancers other than melanoma. Close surveillance of these high-risk families has led to diagnosis of melanoma at an earlier developmental stage, which should result in a decrease in mortality over time. PMID- 8440924 TI - In vivo epiluminescence microscopy: improvement of early diagnosis of melanoma. AB - The majority of pigmented skin lesions can be diagnosed correctly on the basis of clinical criteria; however, there remain a surprisingly high number of small pigmented lesions in which the distinction between melanocytic and non melanocytic and benign and malignant lesions, and thus between melanoma and non melanoma, is difficult or impossible to make with the naked eye. Epiluminescence microscopy is a non-invasive technique that, by use of oil immersion, makes sub surface structures of skin accessible for in vivo microscopic examination and thus provides additional criteria for the diagnosis of pigmented lesions. The technique of epiluminescence microscopy is reviewed, and the significant improvement in the clinical diagnosis of pigmented skin lesions and, in particular, melanoma by this technique is documented. PMID- 8440925 TI - Esophageal disease in AIDS is associated with pathologic processes rather than mucosal human immunodeficiency virus type 1. AB - Twenty-five patients with AIDS and esophageal symptoms were evaluated for the presence of esophageal disease and human immunodeficiency virus type 1 (HIV-1) in the esophageal mucosa. A single infectious process caused by Candida albicans, cytomegalovirus, herpes simplex virus, varicella-zoster virus, or Mycobacterium avium-intracellulare complex or a single noninfectious process caused by Kaposi's sarcoma or reflux esophagitis was identified in 20 patients. Two processes were identified in 5 patients. HIV-1 mRNA was detected by in situ hybridization in mononuclear cells in esophageal lamina propria in 36% of patients. The presence of HIV-1 in the esophageal mucosa was not associated with a specific esophageal symptom, mucosal inflammation or ulceration, Kaposi's sarcoma, specific opportunistic infection, or response of the infection(s) to therapy. Esophageal disease in patients with AIDS appears to be associated with specific pathologic processes rather than the presence of HIV-1 in esophageal mucosa. PMID- 8440926 TI - A human respiratory syncytial virus (RSV) primate model of enhanced pulmonary pathology induced with a formalin-inactivated RSV vaccine but not a recombinant FG subunit vaccine. AB - Human respiratory syncytial virus (RSV) is the leading cause of severe bronchiolitis and pneumonia in infants. RSV vaccine development has been stifled for the past 23 years because infants vaccinated with formalin-inactivated (FI) RSV have experienced exacerbated disease upon RSV infection. This exacerbated disease phenomenon is poorly understood, in part because of the lack of a primate model that exhibits a similar exacerbated disease state. Vaccination of African green monkeys with either FI RSV or a genetically engineered subunit vaccine termed FG glycoprotein reduced replication of challenge virus. However, only vaccination with FI RSV induced an enhanced pulmonary pathologic response to RSV infection. Pulmonary inflammatory scores in the FG glycoprotein-vaccinated monkeys were no greater than in monkeys vaccinated with adjuvant alone. This is the first demonstration of RSV vaccine-induced enhanced pathology in a primate and illustrates that a subunit vaccine has the potential of circumventing this exacerbated disease phenomenon. PMID- 8440927 TI - Antigenic and nucleic acid analysis of nosocomial isolates of respiratory syncytial virus. AB - Monoclonal antibodies and ribonuclease protection were used to analyze antigenic and genomic diversity among 42 isolates of group A respiratory syncytial virus (RSV) from studies of nosocomial RSV carried out at the University of Rochester during the 1974-1975 and 1975-1976 RSV seasons. Three distinct subgroups or lineages and a total of 12 viral variants were present. Against this background of diversity, an outbreak was recognized that included 13 indistinguishable isolates occurring during a 2-week period. This outbreak accounted for 6 of the 8 infants with nosocomial infection. In contrast to the limited diversity of the nosocomial isolates, isolates from the 10 infants with community-acquired infection included 8 variants. Like those from community outbreaks of RSV, isolates of RSV from hospitalized patients are virologically heterogeneous. However, discrete outbreaks associated with transmission of a single strain can occur. PMID- 8440928 TI - Vertical transmission of hepatitis A resulting in an outbreak in a neonatal intensive care unit. AB - Vertical transmission of hepatitis A virus (HAV) has not been reported. From 25 October to 15 November 1989, 10 cases of symptomatic HAV infection occurred among neonatal intensive care unit (NICU) staff. Testing of other NICU staff and patients identified 4 infected infants. Hepatitis A among staff was associated with caring for 1 of these infants, infant A (relative risk [RR], undefined; P = .05). Risk of illness was greater for staff who did not routinely wash their hands after treating infant A for apnea and bradycardia (RR = 4.9; P = .02). Staff, infants, visitors, and transfused blood products could not be implicated as a source of infant A's infection. Infant A's mother, however, was diagnosed with hepatitis A 10 days after premature labor and delivery. Evidence suggests that infant A was infected by his mother before or during birth. HAV then spread within the NICU because of breaks in infection control precautions. To prevent future outbreaks, NICU staff should adhere rigorously to body substance isolation measures. PMID- 8440929 TI - Fecal antibody responses to symptomatic and asymptomatic rotavirus infections. AB - The role of anti-rotavirus fecal IgA (RVflgA) in protecting children against natural rotavirus infections is unclear. Rotavirus outbreaks occurred in each of four day care centers attended by 129 children; 42% of the infections were asymptomatic. RVflgA titers were measured by EIA before infection and 4 weeks later in 50 children who excreted rotavirus (excretors) and in two samples 4 weeks apart from 50 children without detected virus excretion (nonexcretors). Forty-three (86%) excretors and 18 (36%) nonexcretors had a fourfold or greater RVflgA titer rise. Preexposure RVflgA titers were higher in not infected than symptomatic (P = .002), asymptomatic than symptomatic (P = .036), and not infected than asymptomatic children (P = .07). RVflgA titers after asymptomatic infections were slightly than after symptomatic infections (P = .087). In summary, higher RVflgA titers were associated with protection against infection and illness and increased fourfold or more in both asymptomatic and symptomatic children. PMID- 8440930 TI - Effect of age on cytotoxic T lymphocyte memory as well as serum and local antibody responses elicited by inactivated influenza virus vaccine. AB - Healthy seropositive adults aged < 40 (n = 15), 40-64 (n = 15), and > or = 65 (n = 17) years were parenterally immunized with trivalent subvirion influenza virus vaccine, and their cellular and humoral immune responses were compared. Vaccination resulted in a significant enhancement of class I human leukocyte antigen-restricted influenza A cross-reactive cytotoxic T lymphocyte (CTL) memory. Elderly subjects had significantly lower baseline and peak postvaccination mean percentages of specific lysis of influenza A virus-infected autologous targets but nonetheless mounted CTL responses to vaccine that were comparable in magnitude to those of younger adults. Serologic responses and nasal IgG responses to each of 3 vaccine strains were reduced in magnitude and frequency with advancing age. Parenteral immunization was ineffective at inducing nasal wash IgA antibodies. Between 2 and 12 weeks after vaccination, serum and nasal antibody titers decreased modestly, although the rate of decline was comparable between age groups. The ability of elderly adults to mount CTL responses after influenza vaccination suggests that T cell effector mechanisms may be an important determinant of vaccine-induced protection against serious illness in this age group. PMID- 8440931 TI - Safety and immunogenicity of a recombinant protein influenza A vaccine in adult human volunteers and protective efficacy against wild-type H1N1 virus challenge. AB - A recombinant influenza A vaccine (D protein), comprising a carboxy-terminal sequence from the hemagglutinin HA2 subunit of A/Puerto Rico/8/34 virus (H1N1, A/PR/34) fused to 81 amino-terminal residues of the NS1 nonstructural protein, has previously protected mice against influenza A challenge by inducing H1N1/H2N2 cross-reactive cytotoxic T cells (CTL) without hemagglutination-inhibiting (HI) or neutralizing antibody. In our dose-escalating study, the vaccine was safe in humans and induced both IgG and T cell proliferative responses to D protein but little antibody to A/PR/34 or A/Kawasaki/8/86 (H1N1, A/KW/86) viruses. Among an additional group of A/KW/86-seronegative volunteers immunized with 500 micrograms of D protein, none had a rise in serum HI or neutralizing antibody to A/KW/86, 20% had minimal IgG responses to A/KW/86 by EIA, and a minority had any increase in A/KW/86-specific CTL activity. However, viral shedding and clinical illness score were reduced in vaccines relative to A/KW/86-seronegative unimmunized controls after intranasal challenge with wild-type A/KW/86. D protein immunization conferred significant protective immunity not currently explained by any of the immune parameters measured. PMID- 8440932 TI - Immunologic and molecular biologic studies of prion proteins in bovine spongiform encephalopathy. AB - Bovine spongiform encephalopathy (BSE) is a transmissible neurodegenerative disease. Six brain regions from 11 cattle were examined for the presence of the abnormal isoform of the prion protein (PrPBSE). The highest concentrations of PrPBSE were found in the brain stem, where the greatest degree of spongiform change was observed. Molecular cloning of the bovine PrP gene showed that it encodes a protein of 256 or 264 amino acids with five or six Gly:Pro-rich octarepeats, respectively, in contrast to all other mammalian PrP genes, which encode only five octarepeats. The bovine PrP gene is single copy, and the entire open-reading frame lies within a single exon. Since the transmission of prions across species seems to be restricted by differences in PrP sequence, the high degree of homology between sheep and bovine PrP (98%) correlates with the proposed cause of BSE. PMID- 8440933 TI - Pathogen-specific risk factors and protective factors for acute diarrheal disease in urban Brazilian infants. AB - To evaluate potential risk factors and protective factors for acute diarrheal disease in urban infants, 500 infants < or = 12 months old with diarrhea and 500 age-matched control subjects coming to a Sao Paulo emergency room were studied. On multivariate analysis, these apparently sporadic community-acquired cases of diarrhea were significantly associated with hospitalization in the month before onset (odds ratio [OR], 3.4), day care center exposure (OR, 2.0), prior diarrhea in another household member (OR, 4.4), and low family income (OR, 1.8). Breast feeding infants < 6 months old (OR, 0.3) and boiling household drinking water (OR, 0.4) were protective. Enteropathogenic Escherichia coli (EPEC; OR, 12.0) and Salmonella (OR, 7/0, discordant pairs) infections were associated with prior hospitalization, rotavirus infections were associated with day care (OR, 6/0), and breast-feeding was protective against EPEC infections (OR, 0.1). These results suggest that certain preventive strategies can prevent a substantial proportion of cases of diarrheal disease in Brazilian infants. PMID- 8440934 TI - Fibronectin is more active than fibrin or fibrinogen in promoting Staphylococcus aureus adherence to inserted intravascular catheters. AB - To further define the role of fibrin(ogen) and fibronectin in Staphylococcus aureus adherence to central venous catheters, the amount, chemical integrity, and biologic activity of these proteins adsorbed on lines inserted in hospitalized patients were prospectively studied. Polyurethane cannulas promoted a significantly lower adherence of S. aureus than polyvinyl chloride (P < .01) or Hickman (P < .001) cannulas and contained the lowest amount of immunologically assayed fibronectin but not of fibrin(ogen). Fibrinogen showed an extensive loss of adherence-promoting activity on inserted cannulas, which was related to its proteolytic breakdown, as detected by SDS-PAGE and immunoblots with antifibrinogen antibodies and confirmed by in vitro studies with purified protein fragments. In contrast, either intact or fragmented fibronectin, although present in much lower amounts than fibrin(ogen), could actively promote S. aureus adherence onto intravenous catheters. PMID- 8440935 TI - In vitro model of Haemophilus ducreyi adherence to and entry into eukaryotic cells of genital origin. AB - Electron microscopy was used to examine Haemophilus ducreyi adherence to and entry into eukaryotic cells of genital origin. A clinical H. ducreyi isolate (90 244) adhered in snake-like whorls to the surfaces of cervical carcinoma cells (HeLa 229), endometrial adenocarcinoma cells (HEC-1-B), and human neonatal foreskin fibroblast (HFF) cells. A prototype strain of H. ducreyi (CIP542) adhered in randomly organized clumps on the surfaces of HFF. Strain 90-244 entered HFF and HEC-1-B cells but did not enter HeLa cells. The H. ducreyi in the HFF cells at 2 h were partly surrounded by a membrane consistent with that of a phagocytic vacuole. At 2 h, strain CIP542 was found in interstitial spaces between the HFF cells and also in the cytoplasm of the cells. After 7 and 24 h, both strains of H. ducreyi were found in the large interstitial spaces between the HFF cells, in the cytoplasm, and extracellularly. This model of in vitro H. ducreyi infection of eukaryotic cells will allow for more specific study of factors that determine the virulence of H. ducreyi. PMID- 8440937 TI - Nonprotein antigens of Borrelia burgdorferi. AB - Preparative thin-layer chromatograms of chloroform-methanol extracts of Borrelia burgdorferi (B31) sonicates showed four fractions (Rf values of 0.84, 0.81, 0.66 and 0.61) that stained with iodine vapors, orcinol, or phospray, suggesting the presence of lipid-, carbohydrate-, and phosphorus-containing compounds. Sera from patients with Lyme disease showed IgM or IgG antibody reactivity to hydrophobic fractions, designated F1 and F2, in both early and late stages of the disease. Lack of constitutive amino acids in these fractions was shown by protein, amino acid, and peptide detection analyses. Sera from patients with syphilis, systemic lupus erythematosus, and antiphospholipid syndrome reacted to one or both of the fractions. Adsorption of sera from Lyme disease patients with intact B. burgdorferi resulted in significantly different pre- and postadsorption patterns of reactivity by whole cell ELISA, whereas adsorption with F1 and F2 resulted in similar pre- and postadsorption patterns. These fractions may not be present in aqueous whole cell or whole cell lysate ELISA antigens or in immunoblots. PMID- 8440936 TI - Experimental Lyme disease in dogs produces arthritis and persistent infection. AB - Lyme disease was reproduced in specific pathogen-free beagle dogs by exposure to Borrelia burgdorferi-infected ticks (Ixodes dammini). Seroconversion and disease frequency were higher after exposure to infected adult ticks than to infected nymphs. Young pups developed clinical disease more readily than older dogs. The incubation period lasted 2-5 months. Acute recurrent lameness with fibrinopurulent arthritis was the dominant clinical sign. Dogs recovered but developed persistent mild polyarthritis. B. burgdorferi persisted in recovered dogs for at least 1 year. Isolation of B. burgdorferi and detection by polymerase chain reaction was most successful from skin biopsies at the site of the tick bite. Antibody to B. burgdorferi antigens was first detected by ELISA and Western blots by 4-6 weeks after exposure. High serum levels persisted during 17 months of observation. In contrast to infection from ticks, inoculation of dogs with cultured B. burgdorferi resulted in seroconversion with a shorter duration of antibody persistence and no clinical disease. PMID- 8440938 TI - Progression of hearing loss in experimental pneumococcal meningitis: correlation with cerebrospinal fluid cytochemistry. AB - The development of hearing loss and concomitant cerebrospinal fluid (CSF) cytochemical changes in a model of pneumococcal meningitis were examined. Rabbits were injected intracisternally with 10(5) pneumococci. Auditory evoked potentials to clicks and to 10- and 1-kHz tone bursts were recorded hourly; CSF was analyzed every 4 h. Sensorineural hearing loss developed in all animals beginning 12 h after infection and progressed to severe deafness. The onset of hearing loss was preceded by a CSF leukocytosis of > 2000 cells/microL and elevation of CSF protein and lactate concentrations to > or = 1 mg/mL. Temporal bone histopathology showed pneumococci and leukocytes extending from the CSF to the perilymph via the cochlear aqueduct. Hearing loss can develop early in the course of meningitis and is preceded by the abrupt onset of inflammatory changes in CSF. Progression of hearing loss is rapid and proceeds from cochlear base to apex in parallel with the degree of inflammation. PMID- 8440939 TI - Toxoplasmosis acquired during pregnancy: improved serodiagnosis based on avidity of IgG. AB - Serodiagnostic methods were evaluated in prenatal screening for primary Toxoplasma infections acquired during pregnancy in the Helsinki area. Altogether 44,181 sera were obtained consecutively during each trimester from 16,733 mothers. All IgG-containing samples were first examined by a sensitive mu-capture (IgM) ELISA, and positive results were reassessed by IgM immunoblotting and indirect IgM ELISA. An assay measuring the avidity of toxoplasma IgG was used for the first time under screening conditions. Patients suspected to have recent toxoplasmosis were reexamined by IgA ELISA and selectively by the differential agglutination assay (HS/AC test) and IgE ELISA; 16 women with diagnostic increases in IgG titer, 36 with IgM fulfilling strict specificity criteria, and 25 with IgG of low avidity were identified. The measurement of IgG avidity was a highly specific and sensitive method suitable for verification of acute primary Toxoplasma infections during pregnancy. PMID- 8440940 TI - Intensity of infection in AIDS-associated cryptosporidiosis. AB - A fluorescent monoclonal anti-Cryptosporidium antibody was used to count the oocysts in stools of 12 AIDS patients with chronic cryptosporidiosis. Oocyst excretion was present throughout the day in all 12 patients. Stool-to-stool variation in oocyst concentration was within one order of magnitude. Small variations were also found in daily mean oocyst concentration and total daily oocyst excretion in 3 patients who had multiple 24-h stool collections. However, there was a large patient-to-patient variation in mean oocyst concentration (from < 5.0 x 10(3) to 9.2 x 10(5) oocysts/mL) and 24-h total oocyst excretion (from < 6.0 x 10(6) to 1.2 x 10(9) oocysts/day). There was a significant correlation between oocyst excretion and numbers of Cryptosporidium organisms seen on small bowel biopsy. Oocyst excretion was reduced in 4 patients treated with paromomycin, but diarrhea improved only in the 2 patients with high initial oocyst excretion. PMID- 8440941 TI - Prevalence of human immunodeficiency virus types 1 and 2 infections in Nigeria. AB - The prevalence of human immunodeficiency virus (HIV) types 1 and 2 infections in Nigeria was estimated from 3854 serum samples collected at 21 locations from 1985 to 1990. Seventy-eight samples (2.0%) were reactive for HIV-1 and 49 (1.3%) for HIV-2 antibodies; 5 samples were reactive for both viruses. The prevalence of HIV 1 and -2 infections, respectively, was highest among 60 female prostitutes, with 10% and 6.7% positive. For other groups the respective rates of positivity were 4.1% and 3.4% in 610 patients with sexually transmitted diseases, 3.6% and 1.4% in 140 tuberculosis patients, 1.6% and 0.6% of 1253 other medical patients, and 1.2% and 0.9% of 1640 volunteer blood donors. Of 153 health care workers, 1.3% were positive for HIV-1 only. The age group from 20 to 29 years had the highest prevalences of HIV-1 (3.3%) and -2 (2.2%). In Nigeria, antibody prevalence for both viruses appears to have increased > 10-fold between 1986 and 1990. PMID- 8440942 TI - Parvovirus B19-specific DNA in bone marrow from B19 arthropathy patients: evidence for B19 virus persistence. AB - To determine if B19 infection persists in patients with chronic B19 arthropathy, acute B19 infection in adults was documented by IgM serology. Bone marrow aspirates were obtained 24-42 months after acute infection in 4 patients who developed chronic joint symptoms. DNA from bone marrow aspirates was amplified by polymerase chain reaction by using B19-specific DNA sequences in the viral capsid gene and probing with B19-specific oligonucleotides in Southern analysis. B19 specific DNA sequences were detected in all 4 chronic arthropathy patients compared with 0 of 7 anti-B19 IgM-, IgG- and 0 of 6 anti-B19 IgM-, IgG+ normal bone marrow donors. Three patients with serologically proven acute B19 infection and acute but nonchronic joint symptoms had B19 DNA detected in bone marrow aspirates 2-18 months after infection. These findings suggest that B19 arthropathy is associated with persistence of either B19 virus or select B19 DNA sequences. PMID- 8440943 TI - Diffuse and enteroaggregative patterns of adherence of enteric Escherichia coli isolated from aboriginal children from the Kimberley region of Western Australia. AB - Escherichia coli from 138 fecal samples from aboriginal children, in whom no other enteric pathogen was isolated (including enterovirulent E. coli), were examined for HEp-2 cell adhesion. Twenty-five (36.8%) of 68 children with diarrhea and 32 (45.7%) of 70 without diarrhea had diffusely adherent isolates, which were thus not associated with diarrhea (P > .25). However, after age stratification, children > or = 18 months showed a significant association of diffusely adherent E. coli with diarrhea (P < or = .05). Enteroaggregative E. coli were isolated from 12 children with diarrhea (17.6%) and 15 without diarrhea (21.4%); thus, there was no association with diarrhea (P > or = .5). Sixteen children with diarrhea (23.5%) and 6 without diarrhea (8.6%) carried isolates that caused detachment of the HEp-2 cell monolayer from the glass coverslip when examined in the adhesion assay and were significantly associated with diarrhea (P < or = .05). These isolates, termed cell-detaching E. coli, were different from all recognized classes of enterovirulent E. coli. PMID- 8440944 TI - Temporal variation in bacterial disease frequency: molecular population genetic analysis of scarlet fever epidemics in Ottawa and in eastern Germany. AB - In an effort to understand the molecular genetic basis of temporal variation in frequency and severity of bacterial disease, genetic relationships among strains of Streptococcus pyogenes that caused scarlet fever epidemics in Canada in the early 1940s and in eastern Germany in the 1960s to 1980s were studied. Application of multilocus enzyme electrophoresis and comparative sequencing of the gene (speA) encoding streptococcal pyrogenic exotoxin A (scarlet fever toxin) revealed that new waves of scarlet fever are associated with an increase in frequency of S. pyogenes clones carrying variant speA alleles. This finding suggests that the occurrence of new scarlet fever epidemics can be predicted by comprehensive monitoring of the frequency of S. pyogenes clones with variant toxin alleles. PMID- 8440945 TI - Interferon-gamma levels in serum and bronchoalveolar lavage fluid of mice infected with Bordetella pertussis. AB - The adherence of Bordetella pertussis to respiratory cilia and its survival in neutrophils and macrophages is crucial to the pathogenesis of whooping cough. To investigate the role of endogenous interferon (IFN)-gamma in acute infection, levels of IFN-gamma in bronchoalveolar lavage (BAL) fluid of mice infected intranasally with B. pertussis were determined. Since pertussis toxin is released during infection by B. pertussis either locally or systemically, serum levels of IFN-gamma in mice injected intravenously with pertussis toxin were also determined. A persistent and significant increase of IFN-gamma levels with concomitant peripheral blood lymphocytosis was observed after 5 and 10 days. The results of this study showed an early but transitory production of endogenous IFN gamma in BAL fluid of mice infected with B. pertussis. PMID- 8440946 TI - Assessment of candidate anticryptosporidial agents in an immunosuppressed rat model. AB - Cryptosporidium parvum causes life-threatening diarrhea in immunocompromised patients, especially those with AIDS. The efficiency of currently proposed anticryptosporidial therapies is limited or doubtful. In this report, molecular candidates for curative or preventive activity were investigated in an immunocompromised rat model that mimics severe human cryptosporidiosis. No significant anticryptosporidial activity was observed when using sulfadoxine pyrimethamine, quinacrine, trimethoprim-sulfamethoxazole, bleomycin, elliptinium, daunorubicin, pentamidine, alpha-difluoro-methylornithine, diclazuril or N methylglucamine. Vitamin A appeared to reduce oocyst shedding. Active agents included sinefungin (2-10 mg/kg/24 h), lasalocid A (2-10 mg/kg/24 h), metronidazole (25-50 mg/kg/24 h), and sulfadimethoxine (10-100 mg/kg/24 h). Sinefungin (10 mg/kg/24 h) and lasalocid A (10 mg/kg/24 h) displayed the highest anticryptosporidial activity. PMID- 8440947 TI - Induction of heat-shock protein 70 in neutrophils during exposure to subphysiologic temperatures. AB - The expression of heat-shock protein (HSP) 70, a marker of cellular stress, was evaluated in neutrophils. In cells isolated by conventional method, expression of both the inducible HSP72 and the constitutive HSP73 forms of HSP70 was found. This was observed when cells were isolated at room temperature or at 4 degrees C. When autologous plasma was used during the isolation procedure and the entire procedure was done at 37 degrees C, there was no expression of HSP72. Omission of plasma from the isolation procedure done at 37 degrees C also resulted in increased expression of HSP72. These studies demonstrate that the expression of HSP70 in neutrophils is induced by isolation at low temperatures and in the absence of plasma. These observations may be important for studies of the regulation of HSP expression and for other studies that relate to neutrophil activation. PMID- 8440948 TI - Herpes simplex virus infection as a risk factor for human immunodeficiency virus infection in heterosexuals. PMID- 8440949 TI - Beta-lactam antibiotic-induced release of free lipopolysaccharide. PMID- 8440950 TI - Retreatment with recombinant interferon-alpha in patients with chronic hepatitis C. PMID- 8440951 TI - Simultaneous outbreak of Salmonella enteritidis and Salmonella schwarzengrund in a nursing home: association of S. enteritidis with bacteremia and hospitalization. PMID- 8440952 TI - Long-term follow-up of patients with bacterial vaginosis treated with oral metronidazole and topical clindamycin. PMID- 8440953 TI - Pharmacokinetics of an IgM human monoclonal antibody against Pseudomonas aeruginosa in nonseptic patients. PMID- 8440954 TI - Trimethoprim resistance arising in animal bacteria and transferring into human pathogens. PMID- 8440955 TI - The case for immediate post-mastectomy breast reconstruction. PMID- 8440956 TI - ECG of the month. Oops! Defective intraventricular conduction. PMID- 8440957 TI - Necrotizing external otitis. AB - Necrotizing external otitis is a severe osteomyelitis of the temporal bone principally affecting elderly diabetics. It is caused by the gram negative bacillus, Pseudomonas aeruginosa. Clinical findings and diagnosis are reviewed. Long term therapy with intravenous antibiotics is recommended for cure, although newer antimicrobial agents give promise of being successful when administered orally. PMID- 8440958 TI - Spontaneous rupture of splenic hamartoma. AB - Hamartoma of the spleen is a rare benign tumor. Only one spontaneously ruptured splenic hamartoma has been reported that presented with an acute surgical abdomen. A second case of a ruptured hamartoma of the spleen is illustrated; however, this case is unique in that it presented as a nonsurgical abdomen. This case stresses the importance of serial physical examinations of the patient and appropriate diagnostic studies in correctly determining the diagnosis when preliminary findings are inconclusive. Surgeons should include splenic hamartomas in the differential diagnoses of splenic defects seen on radiologic studies or splenic masses palpated during abdominal exploration. PMID- 8440959 TI - Candida pericarditis in a child. AB - We report a case of candida pericarditis in a 12-year-old boy. This is the fourth pediatric case to be reported and the second to have occurred following cardiac surgery. The pathophysiology, diagnosis, and treatment are discussed. PMID- 8440960 TI - Bone marrow transplantation: a children's hospital of New Orleans experience. AB - Bone marrow transplantation has become an important therapeutic strategy in the treatment of pediatric malignancies and certain congenital disorders. We initiated a bone marrow transplant program at Children's Hospital in New Orleans at the start of January 1989. Both allogeneic and autologous bone marrow transplantations have been performed. To date, a total of 20 children have received transplants for a variety of diseases. Their ages ranged from 17 months to 20 years. The overall 2-year survival is 40%. For the good-risk patients, the projected 2-year disease-free survival is 85%, compared to 30% for the poor-risk patients. Regimen-related mortality has been extremely low in our settings primarily due to improvement of available supportive care. We conclude that bone marrow transplantation offers a potential cure for these otherwise fatal diseases. PMID- 8440961 TI - Leprosy in central Louisiana: a few more cases. PMID- 8440962 TI - The ionic basis of the receptor potential of frog taste cells induced by water stimuli. AB - The ionic mechanism underlying the receptor potential induced by a deionized water stimulus was studied in frog taste cells with conventional microelectrodes. The taste cells located in the proximal portion of the tongue generated a depolarizing receptor potential which averaged 10mV in response to stimulation with deionized water. The cell membrane of the water-sensitive taste cell could be divided into the taste-receptive (apical) and basolateral membranes and the cells were classified into two types: Cl(-)-dependent and Cl(-)-independent. In Cl(-)-dependent cells whose input resistance was decreased or unchanged by deionized water, the magnitude of the water-induced depolarization decreased with an increase in concentration of superficial Cl- in contact with the receptive membrane and with addition of blockers of anion channels (0.1 mmol l-1 SITS and 0.1 mmol l-1 DIDS) to deionized water. The reversal potential for the depolarization in this type shifted according to the concentration of superficial Cl-. These properties of the responses were consistent with those of the glossopharyngeal nerve which innervates the taste disc. In Cl(-)-independent cells whose input resistance was increased by deionized water, the reversal potential was approximately equal to the equilibrium potential for K+ at the basolateral membrane. The water-induced response of the glossopharyngeal nerve was decreased to about 60% of the control value by addition of interstitial 2 mmol l-1 Ba2+. It is concluded that the water-induced receptor potential is produced by Cl- secretion through the taste-receptive membrane in about 70% of water-sensitive frog taste cells, while it is generated by an inhibition of the resting K+ conductance of the basolateral membrane in the remaining 30% of the cells. PMID- 8440963 TI - Comparative rheology of human and trout red blood cells. AB - We have studied the comparative rheology of individual red blood cells from humans and rainbow trout (Oncorhynchus mykiss) at their natural body temperatures. Trout red blood cells were large ellipsoids (about 16 microns x 11.5 microns x 2.5 microns) with a mean volume of 250 fl, a surface area of approximately 350 microns 2 and an elongated nucleus of about 9 microns x 5 microns. Although much larger than human red cells (diameter 8 microns, V = 92 fl, A = 136 microns 2), both theoretical calculation and experimental aspiration into micropipettes indicated that the limiting size of a cylindrical vessel that both types of cell could enter was approximately 3 microns. Nevertheless, individual trout red cells had much longer transit times through 5 microns filter pores and were much slower to enter 3-4 microns diameter micropipettes. Interestingly, the relative deformability of the trout cells depended on the pore size and applied pressure, with entry times for trout and human cells converging as pipette diameter increased. The relatively poor overall cellular deformability of the trout cells reflected their membrane rigidity (shear elastic modulus 4-5 times higher than that of human membrane), as well as their large size and the presence of a prominent nucleus. Capillary diameters in trout muscle are similar to those in the human microcirculation (about 3 microns), while systemic driving pressures are much lower. Therefore, either red cell deformability is a less critical circulatory parameter than has previously been thought, or the apparently disadvantageous blood rheology of trout is adequate because of the lower demand for tissue perfusion. PMID- 8440964 TI - Cardiac responses of grey seals during diving at sea. AB - Heart rate, swimming speed and diving depth data were collected from free-ranging grey seals, Halichoerus grypus, as they foraged and travelled in the sea around the Hebrides Islands off western Scotland. Information was collected on a tracking yacht using a combination of sonic and radio telemetry. Diving heart rate declined as a function of dive duration. In long dives, grey seals employed extreme bradycardia, with heart rates falling to 4 beats min-1 for extended periods, despite the animal being free to breath at will. This extreme dive response is part of the normal foraging behaviour. Seals spent 89% of the time submerged during bouts of long dives; swimming was restricted to ascent and descent. Dive durations exceeded estimated aerobic dive limit, even assuming resting metabolic rates. These results indicate that behavioural, and possibly cellular, energy-sparing mechanisms play an important role in diving behaviour of grey seals. This has implications not only for studies of mammalian energetics but also for our understanding of the foraging tactics and prey selection of marine mammals. If some seals are using energy-sparing mechanisms to reduce metabolic costs while at depth, they may be forced to wait for and ambush prey rather than to search for and chase it. PMID- 8440965 TI - Identification, characterisation and in vitro reconstruction of an interneuronal network of the snail Helisoma trivolvis. AB - 1. We describe three interneurones and their follower cells in the central ganglionic ring of Helisoma trivolvis. 2. The largest neurone on the dorsal surface of the left pedal ganglion is shown to be an interneurone that contains dopamine and makes monosynaptic connections with a large number of follower cells in the visceral and left parietal ganglia. This neurone is designated as left pedal dorsal 1 (LPeD1). 3. Another giant neurone is located on the dorsal surface of the right pedal ganglion. Although the position and morphology of this cell, designated right pedal dorsal 1 (RPeD1), are similar to those of LPeD1, it contains serotonin rather than dopamine. This neurone was found to synapse only on LPeD1, no other follower cells have so far been discovered. The connections between LPeD1 and RPeD1 are mutually inhibitory. 4. A small FMRFamide immunoreactive neurone, identified here as visceral dorsal 4 (VD4), is located on the dorsal surface of the visceral ganglion. This neurone has a large number of follower cells throughout the central ganglionic ring. Among these follower cells are LPeD1 and RPeD1. The transmitter utilized by VD4 at these synapses is probably FMRFamide. In addition, VD4 receives excitatory inputs from LPeD1 that appear to be chemical and monosynaptic. 5. To test further the monosynaptic and specific nature of the connections within the network, the three interneurones were isolated and cultured in vitro. In these circumstances, the three neurones extended neurites and formed synapses which, with one exception (occasional electrical coupling between LPeD1 and RPeD1), were of similar type to those observed in vivo. 6. The identification and characterization of these three interneurones and their follower cells should greatly facilitate future studies of the Helisoma trivolvis nervous system. Furthermore, the possibility that this three-cell network can be reconstructed in vitro should aid our understanding of the mechanisms underlying synapse formation and neuronal plasticity. PMID- 8440966 TI - Odor sensitivity of cultured lobster olfactory receptor neurons is not dependent on process formation. AB - Cultured lobster olfactory receptor neurons (ORNs) were surveyed for their odor sensitivity with whole-cell, voltage-clamp recording. The nature of the adequate stimuli, the degree of tuning (response spectra) of the cells, the threshold of sensitivity and the dual polarity of the odor-evoked currents are consistent with chemosensitivity in the cultured ORNs being olfactory. The ability of odors to evoke currents in cultured ORNs that lack processes suggests that lobster ORNs can be induced in vitro to insert all the elements of the transduction cascade in the soma, including those that might normally be confined to processes. This should greatly facilitate analysis of olfactory transduction in these cells. PMID- 8440967 TI - Bulk flow of the medium and cutaneous sodium uptake in frogs: potential significance of sodium and oxygen boundary layers. AB - To examine the potential impact of fluid dynamic boundary layers on cutaneous ion exchange, we investigated how bulk flow of dilute Na+ solutions (< or = 1.0 mmol l-1) over the skin of intact frogs (Rana catesbeiana and Rana pipiens) affects cutaneous Na+ uptake (JNa(in)) and transepithelial potential (TEP). Cessation of stirring resulted in a 14-35% decrease in TEP and a 14-65% decrease in JNa(in). Two weeks' acclimation to an unstirred bath increased JNa(in) to levels 70% greater than in frogs acclimated to a continuously stirred bath and to levels comparable to those of frogs acclimated to deionized water. These effects are consistent with depletion of Na+ in the boundary layer, but are also consistent with depletion of O2 in the boundary layer, which might limit generation of ATP consumed by ATPases responsible for cutaneous Na+ uptake. To investigate this latter possibility, we measured TEP and JNa(in) while manipulating the PO2 of well-stirred external media at constant [Na+]. Hyperoxia (PO2 > or = 97 kPa) increased JNa(in) by 28% and had little or no effect on TEP. Hypoxia (PO2 < or = 1.5 kPa) reduced JNa(in) by 48% and decreased TEP by 22%. These results suggest that ionic and gaseous boundary layers may interact to affect cutaneous ion transport. PMID- 8440968 TI - Mammalian spinal biomechanics. I. Static and dynamic mechanical properties of intact intervertebral joints. AB - Four-point bending was used to apply pure extension and flexion moments to the ligamentous lumbosacral spine and pelvic girdle of monkey (Macaca fascicularis), rabbit (domestic and wild, Oryctolagus cuniculus), badger (Meles meles), wallaby (Wallabia rufogrisea frutica), sheep (Ovis aries), seal (Phoca vitulina) and tiger (Panthera tigris). The absolute ranges of angular change in lumbar-lumbar joints (from X-radiographs) were considerable and similar in monkey and wallaby (greater in flexion) and in rabbit and badger (symmetrical in extension and flexion). Mass-specific bending comparisons showed that monkey and seal joints were the most and least resistant, respectively, to these moments. The patterns of mobility showed no clear scaling effects. Subsequently, additional ligamentous joint complexes (three vertebrae and two intervertebral discs) of monkey, wallaby, tiger, jaguar (Panthera onca) and seal (Halichoerus grypus) were subjected to cyclic extension and flexion moments. Changes in intervertebral angle (y, from X-radiographs) were modelled as functions of applied specific bending moments (x):y=A(1-e-Bx). A and B values represented bending capacities and joint compliances respectively. Homologous monkey and wallaby joints had considerable flexion capacities, with low compliances. Homologous jaguar and tiger joints had limited flexion capacities, but greater compliances. The data suggest that flexion resistance may be controlled by different mechanisms in different species. PMID- 8440969 TI - Mammalian spinal biomechanics. II. Intervertebral lesion experiments and mechanisms of bending resistance. AB - Three-point cyclic bending was applied to intervertebral joint complexes (three vertebrae with two intervertebral discs) of monkey (Macaca fascicularis), wallaby (Wallabia rufogrisea frutica), tiger (Panthera tigris), jaguar (Panthera onca) and seal (Halichoerus grypus). Force-displacement loops were recorded for intact specimens in both extension and flexion. Reductions in peak forces at given displacements were measured, following lesions of ventral ligaments, superspinous ligaments, interspinous ligaments and muscles, ligamenta flava and the articular capsules. Subsequently, the vertebral arches were removed from the specimens to test the bending resistance of the intervertebral discs alone. The results of these lesion experiments, coupled with details of intervertebral joint anatomy, suggest that extension resistance is ultimately due to articular joint impaction for all species tested. The prominent ligamenta flava of the monkey and wallaby contrast with the robust discs of jaguar and tiger and illustrate two distinct mechanisms for resisting flexion in mammalian intervertebral joints. The conspicuous absence of soft structural elements in seal intervertebral joints contributes to their low bending resistance. The implications of these findings for mammalian locomotion, behaviour and scaling are discussed. PMID- 8440970 TI - Energetic cost of locomotion as a function of ambient temperature and during growth in the marsupial Potorous tridactylus. AB - In the marsupial, the potoroo, multiple regression analysis shows that ambient temperature makes a minor (2%) contribution towards variation in oxygen consumption with speed. This suggests that the heat generated during running is substituted for heat which would otherwise have to be generated for temperature regulation. Maximum levels of oxygen consumption are also temperature-independent over the range 5-25 degrees C, but plasma lactate concentrations at the conclusion of exercise significantly increase with ambient temperature. Adult potoroos show a linear increase in oxygen consumption with speed, and multiple regression indicates that the most significant factor affecting energy use during running is stride length. Juvenile potoroos have an incremental cost of locomotion about 40% lower than that predicted on the basis of body mass. The smaller animals meet the demands of increasing speed by increasing stride length rather than stride frequency, as would be expected in a smaller species. Our results show that juvenile potoroos diverge significantly from models based only on adult animals in incremental changes in stride frequency, length and the cost of transport, suggesting that they are not simply scaled-down adults. PMID- 8440971 TI - Osmoregulation in the parasitic nematode Pseudoterranova decipiens. AB - When subjected to hyper- or hypo-osmotic stress at 5 degrees C for 24 h, third stage larvae of the parasitic nematode Pseudoterranova decipiens do not exhibit changes in mass or in the osmotic pressure of the pseudocoelomic fluid. Immersion in solutions containing 3H2O demonstrates that exchange with the water in the pseudocoelomic fluid is substantially complete within 24 h. Sacs composed of cylinders of body wall without the intestine and pseudocoelomic fluid do not gain weight when immersed for 24 h in hypotonic medium. Metabolic poisons abolish the ability of whole worms and sacs to maintain their weight when immersed in hypotonic media. These observations support the conclusion that the nematode is capable of at least short-term osmoregulation and that the site of osmoregulation is the body wall. The observations that more fluid is passed from the anus in some hypo-osmotically stressed worms and that worms ligatured at the tail exhibit a small increase in mass when exposed to hypo-osmotic conditions may indicate that the intestine plays a minor and subsidiary role in osmoregulation. PMID- 8440972 TI - Water compartments and osmoregulation in the parasitic nematode Pseudoterranova decipiens. AB - A study of the time course of penetration of 3H2O into whole worms suggests that worms immersed in a hypo-osmotic environment (15% artificial sea water) reach full exchange equilibrium more slowly than worms in an iso-osmotic environment (40% artificial sea water). The apparent water content, determined by dry mass, matches that determined by 3H2O exchange when worms are immersed for 24 h in 40% artificial sea water (ASW), but the water content measured by 3H2O exchange is lower when worms are kept in a hypo-osmotic environment for 24 h. These differences disappear after 48 h. No such differences are apparent when sacs, consisting of cylinders of body wall lacking their intestines and pseudocoelomic fluid and closed at both ends by ligatures, are immersed in either 40% or 15% ASW for 24 h. The placing of ligatures at the head, but not at the tail, results in a failure of worms immersed in 40% ASW or 15% ASW containing 3H2O to achieve full exchange equilibrium within 24 h. These results suggest that although worms immersed in an iso-osmotic environment drink, those immersed in a hypo-osmotic environment do not, a conclusion supported by studies involving the addition of [14C]inulin to the medium. The application of ligatures to the head and tail of worms immersed in 40% ASW results in a slower penetration of 3H2O into the pseudocoelomic fluid, whereas similar ligatures do not further retard the penetration in worms exposed to 15% ASW. The results are consistent with a model which sees the pseudocoelomic fluid as consisting of two compartments containing water, one of which exchanges more slowly than the other. PMID- 8440973 TI - Motor neuron M3 controls pharyngeal muscle relaxation timing in Caenorhabditis elegans. AB - 1. Previous work has shown that 12 of the 14 types of neurons in the Caenorhabditis elegans pharyngeal nervous system are collectively but not individually necessary for the trapping and transport of bacteria. The aim of these experiments was to determine the functions of individual neuron types by laser-killing combinations of neurons and looking at the effects on behavior. 2. The motor neuron M3 and the sensory neuron I5 are important in trapping bacteria, as shown by two observations. First, when M3 and I5 are both killed, trapping is inefficient in the isthmus (the middle section of the pharynx). Second, M3 is sufficient in the absence of the other 11 neuron types for normal trapping in the corpus (anterior pharynx). 3. M3 and I5 influence the timing of pharyngeal muscle motions. When M3 is killed, pump duration (the interval from the beginning of pharyngeal contraction to the end of relaxation) increases from 170 to 196 ms. This increase is at least partially due to a slower relaxation. Thus, M3 speeds up relaxation. Pump duration decreases to 159 ms when I5 is killed. When I5 and M3 are both killed, pump durations are long (192 ms), just as when M3 alone is killed. These observations, together with previous electron microscopic work showing synapses from I5 to M3, suggest that I5 slows down relaxation by inhibiting M3. 4. To explain these results, I propose that M3 and I5 promote bacterial trapping by regulating the relative timing of muscle relaxation in different regions of the pharynx. PMID- 8440974 TI - Voltage-clamp frequency domain analysis of NMDA-activated neurons. AB - 1. Voltage and current-clamp steps were added to a sum of sine waves to measure the tetrodotoxin-insensitive membrane properties of neurons in the intact lamprey spinal cord. A systems analysis in the frequency domain was carried out on two types of cells that have very different morphologies in order to investigate the structural dependence of their electrophysiological properties. The method explicitly takes into account the geometrical shapes of (i) nearly spherical dorsal cells with one or two processes and (ii) motoneurons and interneurons that have branched dendritic structures. Impedance functions were analysed to obtain the cable properties of these in situ neurons. These measurements show that branched neurons are not isopotential and, therefore, a conventional voltage clamp analysis is not valid. 2. The electrophysiological data from branched neurons were curve-fitted with a lumped soma-equivalent cylinder model consisting of eight equal compartments coupled to an isopotential cell body to obtain membrane parameters for both passive and active properties. The analysis provides a quantitative description of both the passive electrical properties imposed by the geometrical structure of neurons and the voltage-dependent ionic conductances determined by ion channel kinetics. The model fitting of dorsal cells was dominated by a one-compartment resistance and capacitance in parallel (RC) corresponding to the spherical, non-branched shape of these cells. Branched neurons required a model that contained both an RC compartment and a cable that reflected the structure of the cells. At rest, the electrotonic length of the cable was about two. Uniformly distributed voltage-dependent ionic conductance sites were adequate to describe the data at different membrane potentials. 3. The frequency domain admittance method in conjunction with a step voltage clamp was used to control and measure the oscillatory behavior induced by N-methyl-D aspartate (NMDA) on lamprey spinal cord neurons. Voltage-clamp currents and impedance functions were measured at different membrane potentials. The impedance functions had a voltage-dependent resonance and phase shift characteristic of a negative conductance. These measurements provide a quantitative analysis of the conductances induced by NMDA in central neurons of the lamprey spinal cord and directly establish the basis of the non-linear oscillatory behavior previously observed in the presence of NMDA. NMDA was shown specifically to activate a negative and a positive conductance, both of which were markedly affected by the membrane potential. It is shown that the net current in the presence of NMDA must be considered as the algebraic sum of currents in opposite directions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8440975 TI - The paradigm and the fuzzy logical model of perception are alive and well. AB - Cutting, Bruno, Brady, and Moore (1992) criticized the paradigm for inquiry and the fuzzy logical model of perception (FLMP) presented in Massaro (1988a). In this reply to their remarks, it is shown that (a) the properties of the paradigm are ideal for inquiry; (b) models are best tested against the results of individual subjects and not average group data; (c) model fitting and analysis of variance do not give contradictory results; (d) the FLMP can be proven false and does not have a superpower to predict a plethora of functions or to absorb random variability; and (e) various extraneous characteristics of a model, such as equation length, cannot account for the success of the FLMP. On the other hand, the empirical findings of Cutting et al. give important new properties of pattern recognition. Finally, Cutting's theory of directed perception is compared with the FLMP. PMID- 8440976 TI - Mechanisms involved in the observational conditioning of fear. AB - Three experiments support the hypothesis that mechanisms involved in observational conditioning (OC) of fear are similar to those of direct classical conditioning and involve the organism attempting to detect the causal structure of its environment. Experiment 1, a correlational analysis, shows that model monkeys' fear behaviors on snake trials (unconditioned stimulus [US]) were highly correlated with observer monkeys' fear (unconditioned response) while watching the models' fear. In Experiment 2, all observers showed distress while watching the model's fear during Session 1 of OC, but only observers who could see the snake to which the model was reacting continued to show fear during subsequent OC sessions, suggesting that the model's fear is an easily habituable US. In Experiment 3, observers acquired significant fear of snakes after 1 OC session, indicating that the continued fear of those Experiment 2 observers that could see the snake may reflect their own acquired fear of snakes. PMID- 8440977 TI - Mirror-image matching and mental rotation problem solving by baboons (Papio papio): unilateral input enhances performance. AB - Three experiments, using a matching-to-sample procedure, were conducted to examine hemispheric specialization in mirror-image discrimination and mental rotation in baboons (Papio papio). In Experiment 1, no significant difference was found in discrimination of mirror-image and asymmetric pattern stimuli. In Experiment 2, orientation discrimination was assessed within the left (LVF) and right (RVF) visual half-fields. An RVF advantage was found in accuracy for asymmetric patterns, whereas an LVF advantage was found for discrimination of mirror-image stimuli. No significant relation was found between angular disparity of the stimuli and response time. Experiment 3 examined the effect of bilateral visual input on accuracy and response time. Significantly lower accuracy and longer response times were found for bilateral compared with unilateral visual input. PMID- 8440978 TI - Nonvisual navigation by blind and sighted: assessment of path integration ability. AB - Blindfolded sighted, adventitiously blind, and congenitally blind subjects performed a set of navigation tasks. The more complex tasks involved spatial inference and included retracing a multisegment route in reverse, returning directly to an origin after being led over linear segments, and pointing to targets after locomotion. As a group, subjects responded systematically to route manipulations in the complex tasks, but performance was poor. Patterns of error and response latency are informative about the internal representation used; in particular, they do not support the hypothesis that only a representation of the origin of locomotion is maintained. The slight performance differences between groups varying in visual experience were neither large nor consistent across tasks. Results provide little indication that spatial competence strongly depends on prior visual experience. PMID- 8440979 TI - Perceptual manifestations of an analytic structure: the priority of holistic individuation. AB - Properties that make items perceptually distinctive may not be represented in the dimensional structure used by subjects for analysis. In a classification task, a single dimensional structure, actually used by subjects when analyzing, occurred in several perceptual forms. Two types of perceptual variation were compared: (a) feature individuation, whether a feature occurs in a unique form in different items and (b) holistic individuation, the extent to which an item's features cohere into an individuated whole. These types of individuation had separate effects on exemplar-based classification. However, holistic individuation had priority in that the presence of individuated features did not produce exemplar based transfer if the item's holistic properties were altered. This priority of holistic individuation occurred whether the subjects had been given the classification rule or had attempted to discover it. PMID- 8440980 TI - Measuring the effect of attention on simple visual search. AB - Set-size in visual search may be due to 1 or more of 3 factors: sensory processes such as lateral masking between stimuli, attentional processes limiting the perception of individual stimuli, or attentional processes affecting the decision rules for combining information from multiple stimuli. These possibilities were evaluated in tasks such as searching for a longer line among shorter lines. To evaluate sensory contributions, display set-size effects were compared with cuing conditions that held sensory phenomena constant. Similar effects for the display and cue manipulations suggested that sensory processes contributed little under the conditions of this experiment. To evaluate the contribution of decision processes, the set-size effects were modeled with signal detection theory. In these models, a decision effect alone was sufficient to predict the set-size effects without any attentional limitation due to perception. PMID- 8440981 TI - Location dominance in attending to color and shape. AB - Four experiments investigated whether Ss direct attention to stimulus location when attempting to attend to its color or shape. In the first 2 experiments a given property (location, color, or shape) of a letter cue instructed Ss whether to report any letters from a subsequent display. Regardless of which property was relevant, Ss reported letters adjacent to the cue and not those similar to its color or shape. In the last 2 experiments, the varied location of a cue was irrelevant to the task, whereas its varied color instructed Ss to report a letter in a given location or of a given shape. Targets adjacent to the cue were reported faster than those remote from the cue. The results suggest that attempting to attend to any aspect of a stimulus entails directing attention to its location. PMID- 8440982 TI - Role of image acceleration in judging landing location of free-falling projectiles. AB - The vertical acceleration of the projective image of a free-falling object specifies whether the object will land behind or in front of the observation site. Human sensitivity to this visual cue was investigated in 4 studies. Experiments 1 and 2 examined sensitivity to both constant and accelerating vertical acceleration. Detection of acceleration required a total change in velocity that was about 20% of the average velocity. In Experiments 3 and 4, subjects judged where computer-simulated free-falling objects would land relative to the observation site by viewing the initial segment of the flight objects whose trajectories remained in the sagittal plane of the observer. Judgments were influenced significantly by the magnitude and direction of the image velocity change even when no error feedback was available, implicating image acceleration as a source of information for judging the landing site of free-falling objects. PMID- 8440983 TI - Similar attentional, frequency, and associative effects for pseudohomophones and words. AB - Between the presentation and recall of 1 or 5 digits, Ss performed a secondary task of naming a visually presented letter string--a pseudohomophone (e.g., FOLE, HOAP) or its real-word counterpart (FOAL, HOPE). Memory load interacted with frequency (HOPE vs. FOAL, HOAP vs. FOLE) but not with lexicality (HOPE vs. HOAP, FOAL vs. FOLE). This outcome counters models in which nonwords are named by a slow (resource-expensive) process that assembles phonology and words are named by a fast (resource-inexpensive) process that accesses lexical phonology. When the associative priming-of-naming task was secondary to the memory task, pseudohomophone associative priming (HOAP-DESPAIR, FOLE-HORSE) equaled associative priming (HOPE-DESPAIR, FOAL-HORSE) and was affected in the same way by memory load. Assembled phonology seems to underlie the naming of both words and nonwords. PMID- 8440984 TI - Optical information about the severity of upcoming contacts. AB - The time derivative (tau) of the inverse of the relative rate of optical expansion (tau) may have critical values with potential implications for controlling activity. The present research addresses the particular hypothesis that tau < -0.5 specifies "unsafe" collision courses and tau > or = -0.5 specifies "safe" collision courses. Optical expansion patterns were simulated on a computer with -1.0 < or = tau < 0 and judged as suggesting a "hard" or "soft" collision. tau < -0.5 led to significantly different decisions from tau > or = 0.5, but the critical value of -0.5 was not perceived reliably as soft, a deviation possibly due to discretely approximating continuous functions. Additional experiments evaluated terminal rates of change and display duration and examined the effects of biasing the presented displays toward the soft or the hard end of the tau continuum. The results were consistent with the tau hypothesis. PMID- 8440985 TI - Things that go bump in the light: on the optical specification of contact severity. AB - Psychologists are intrigued with the idea that optical variables can specify not only the time until an object impacts an observer but also the severity of the impact. However, the mapping between the optical variables (tau and .tau) and the kinematic variables (velocity, acceleration) has been misstated, erroneously implying that there exist critical values of the optical variables used for locomotion and control. In this commentary, the mathematical relationship between the optical and kinematic variables is reexamined and the erroneous assumptions that have led to the proposal of critical values are show. Also examined are the empirical data on deceleration to approach (particularly from active control paradigms) to assess whether the proposed optical variables are likely candidates for control strategies. Finally, problems associated with numerical approximations to dynamic systems, particularly when analytic solutions exist, are discussed. PMID- 8440986 TI - Representation of acoustic events in the primary auditory cortex. AB - One approach to the problem of specifying the contribution of the primary auditory cortex to auditory perception has been based on single-neuron recording techniques in animals. These experiments measure the response rates of individual neural elements to parametric variations in 1 or more stimulus dimensions. The patterns of response rates and response failures revealed by these manipulations are quantitative descriptions of the form and fidelity of the cortex's representation of those stimulus dimensions. This strategy has been used to advantage in studies of the cortical representation of the spectral content of auditory events, the spatial location of a sound, and the time structure of sounds. The data constitute new links between neural coding and behavioral performance in normal and impaired listeners. PMID- 8440987 TI - Depth perception in motion parallax and stereokinesis. AB - Perceived depth in the stereokinetic effect (SKE) illusion and in the monocular derivation of depth from motion parallax were compared. Motion parallax gradients of velocity can be decomposed into 2 components: object- and observer-relative transformations. SKE displays present only the object-relative component. Observers were asked to estimate the magnitude and near-far order of depth in motion parallax and SKE displays. Monocular derivation of depth magnitude from motion parallax is fully accounted for by the perceptual response to the SKE, and observer-relative transformations absent in the SKE are of perceptual utility only as determinants of the near-far signing of perceived sequential depth. The amount of depth and rigidity perceived in motion parallax and SKE displays covaries with the projective size of the stimuli. The monocular derivation of depth from motion is mediated by a perceptual heuristic of which the SKE is symptomatic. PMID- 8440988 TI - An objective criterion for apparent motion based on phase discrimination. AB - Studies of visual apparent motion have relied on observers' subjective self reports of experienced motion, for which there is no objective criterion of right or wrong. A new method of phase discrimination is reported that may offer an objective indicator of apparent motion. Ss discriminated the direction of an objective 75-ms phase shift, away from strict temporal alternation of 2 stimulus dots. Accuracy increased from 50% to 100% correct as rate of alternation and distance between the dots was decreased, in conformity with Korte's third law of apparent motion. This and additional evidence suggests that phase discrimination may be mediated by asymmetries between the experienced strengths of leftward and rightward motion. Phase discrimination may also be adaptable to the study of apparent motion and related phenomena in other sensory modalities and other animal species. PMID- 8440989 TI - Bistability and hysteresis in the organization of apparent motion patterns. AB - In a paradigm for which 2 distinct patterns are perceived for the same stimulus, perceptual hysteresis (persistence of a percept despite parameter change to values favoring the alternative pattern) and temporal stability (persistence despite intrinsic propensities toward spontaneous change) are interdependent. Greater persistence during parameter change reduces temporal stability, slowing the rate of parameter change reduces hysteresis by increasing opportunity for spontaneous change, and increasing temporal stability (by enlarging the stimulus) increases hysteresis. Hysteresis results in the perception of parametrically disfavored patterns; a parameter can influence a percept without specifying it. The visual system thus exhibits time-dependent behavior analogous to dynamical behavior observed in other systems, both physical and biological, for which there is competition among alternative patterns that vary in relative stability. PMID- 8440990 TI - Stimulus-response compatability for moving stimuli: perception of affordances or directional coding? AB - Michaels reported a compatibility effect in which responses were fastest at the destination of a moving stimulus; she interpreted this "destination" compatibility effect in terms of catching actions "afforded" by the stimulus motion. The present study evaluated implications of the catching-affordance account and compared them with those of an account based on spatial coding of relative direction. The destination compatibility effect was obtained when the responses were keypresses rather that catching movements of a joystick and regardless of whether the stimulus expanded, contracted, or only changed location. This effect was a function of relative rather than absolute location of the responses. A similar compatibility effect was obtained when destinations were designated by static arrow stimuli. The results are inconsistent with the catching-affordance account and are best explained by the coding of relative direction. PMID- 8440991 TI - Transitions in learning: evidence for simultaneously activated strategies. AB - Children in transition with respect to a concept, when asked to explain that concept, often convey one strategy in speech and a different one in gesture. Are both strategies activated when that child solves problems instantiating the concept? While solving a math task, discordant children (who produced different strategies in gesture and speech on a pretest) and concordant children (who produced a single strategy) were given a word recall task. All of the children solved the math task incorrectly. However, if discordant children are activating two strategies to arrive at these incorrect solutions, they should expend more effort on this task than concordant children, and consequently have less capacity left over for word-recall and perform less well on it. This prediction was confirmed, suggesting that the transitional state is characterized by dual representations, both of which are activated when attempting to explain or solve a problem. PMID- 8440992 TI - Vestibular (acoustic) schwannomas: histologic features in neurofibromatosis 2 and in unilateral cases. AB - Unilateral vestibular schwannomas (VS) differ from those in patients with neurofibromatosis 2 (NF-2) clinically and by in situ appearance. To determine whether there are histopathologic differences, the presence of each of 16 histologic features was compared in first surgical resection specimens of 48 VS from 39 NF-2 patients and 293 unilateral VS. Antoni A and B areas, nuclear atypia, whorls, scarring, chronic inflammation, and sheets of macrophages were found equally in both groups. Vestibular schwannomas in NF-2 had more Verocay bodies, foci of high cellularity, and lobular growth patterns, the latter possibly correlating with in situ appearance. Ten NF-2 VS specimens had either meningiomas or microscopic meningeal cell proliferations removed with the VS from the same area, whereas none of the patients with a unilateral VS had these findings. Unilateral VS had more hyalinized and malformed vessels, recent and old thromboses and hemosiderin deposits. The differences could not be attributed to patient ages because there were similar differences between the VS in NF-2 and the unilateral VS of 40 patients age-matched to the NF-2 patients. There were more female patients in both groups, but gender did not influence the occurrence of any histologic features. There were nine additional patients with apparently unilateral VS but in whom the diagnosis of NF-2 was suggested by additional findings; six of the VS from these patients had lobular patterns.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8440993 TI - Localization and quantitation of the chromosome 6-encoded dystrophin-related protein in normal and pathological human muscle. AB - A dystrophin-related protein (DRP) encoded by a gene on chromosome 6 was studied in 14 normal and 79 pathological human skeletal muscle biopsies, as well as in cultured myotubes by light microscopic immunocytochemistry and quantitative immunoblots. In normal muscle immunoreactive DRP was present at the postjunctional surface membrane, at the surface of satellite cells, in the walls of blood vessels, in Schwann cells and in perineurium of intramuscular nerves. All of this produced a weak signal on immunoblots. In Duchenne/Becker dystrophy (DMD/BMD) and in polymyositis (PM) or dermatomyositis (DM) DRP was present throughout the extrajunctional surface membrane of extra- and intrafusal muscle fibers, particularly regenerating ones. This produced a 15-17-fold increase of DRP over normal in DMD/BMD and 4-10-fold increase over normal in PM and DM on immunoblots. In other pathological muscles, DRP localization pattern and quantity was about the same as in normals. Dystrophin-related protein was present in about the same amounts and distribution in normal and DMD cultured myoblasts and myotubes. The molecular stimulus for the marked upregulation of DRP in DMD/BMD and in the inflammatory myopathies is not known. In DMD/BMD the diffuse sarcolemmal DRP may partially compensate for dystrophin deficiency. PMID- 8440994 TI - SP-40,40 immunoreactivity in inflammatory CNS lesions displaying astrocyte/oligodendrocyte interactions. AB - Immunoreactivity for SP-40,40, a putative complement inhibitor, adhesion or protective molecule, has been examined in a variety of inflammatory CNS lesions that displayed associations between hypertrophic astrocytes and oligodendrocytes, a phenomenon previously suggested to be related to oligodendrocyte phagocytosis or protection. SP-40,40 staining was common and was predominantly limited to hypertrophic astrocytes within lesion areas and diminished beyond the lesion margin. However, there was no consistent relationship between SP-40,40 immunoreactivity and astrocytes associated with oligodendrocytes. Staining for terminal complement complex (C5b-9/SC5b-9) occurred in association with larger vessel walls and microglial cells in the most active lesions, but was never seen in hypertrophic astrocytes. No association between SP-40,40 and complement deposition could be demonstrated. Staining for tumor necrosis factor-alpha showed a few scattered hypertrophic astrocytes to be positive. The findings confirm the presence of these astrocyte/oligodendrocyte interactions in active CNS lesions of varied etiology (multiple sclerosis, stroke and AIDS encephalitis). SP-40,40 immunoreactivity was common to hypertrophic astrocytes regardless of their associations with oligodendrocytes but showed no colocalization with terminal complement complex. Thus, these glial interactions do not apparently involve protection against complement-mediated lysis. Furthermore, the presence of SP 40,40 in astrocytes lacking association with oligodendrocytes did not support a role for this protein functioning as an adhesion molecule in astrocyte/oligodendrocyte associations. PMID- 8440995 TI - Temporal sequence of plaque formation in the cerebral cortex of non-demented individuals. AB - One of the hallmarks of Alzheimer's disease is the presence of argyrophilic plaques (arg-P) accompanying dementia and other forms of cognitive alterations. In the present investigation 195 non-demented, cognitively normal patients were grouped according to the presence or absence of critical coronary artery disease (cCAD), defined as a 75% or greater stenosis of one of the epicardial arteries. None of the subjects had significant cerebral vascular disease. The parahippocampal gyrus (PHG) and frontal pole were analyzed for the presence of arg-P, A4 deposition, ALZ-50 immunoreactive (IR) neurons and neuropil threads (NT). Individuals with cCAD have a significantly greater incidence of plaques than non-heart disease (non-HD) subjects. Every cCAD subject had ALZ-50 IR neurons in the PHG and a greater incidence of NT as compared to the non-HD subjects. Every subject with plaques also had IR neurons and NT in the PHG. Based on the presumption that early neurodegeneration labeled by ALZ-50 antibody and amyloid deposition are in some way linked, then the sequence of plaque formation is initiated by the presence of ALZ-50 IR neurons followed in order by NT, A4 deposition and diffuse form arg-P. PMID- 8440996 TI - The use of antibodies targeted against the neurofilament subunits for the detection of diffuse axonal injury in humans. AB - Axonal injury is a common feature of human traumatic brain injury. Typically, damaged axons cannot be recognized unless a patient survives the injury by at least 10-12 hours (h). Limitations associated with the use of the traditional silver methods have been linked with this inability to recognize early posttraumatic reactive axonal change. Recently, we reported that antibodies targeting the neurofilament subunits proved useful in recognizing early traumatically induced axonal change in traumatically brain-injured animals. Accordingly, in the present communication, we employed antibodies to detect at the light microscopic level the 68 kD Nf-L and 170-200 kD Nf-H neurofilament subunits in head-injured patients who survived the traumatic event for periods ranging from 6 h to 59 days. Antibodies targeting all of the above-described subunits revealed a progression of reactive axonal change. Antibodies to the 68 kD subunit proved most useful, as they were not complicated by concomitant immunoreactivity in surrounding nuclei and/or dendritic and somatic elements. These immunocytochemical strategies revealed, at 6 h postinjury, focally swollen axons which appeared intact. By 12 h, this focal swelling had progressed to disconnection, with the immunoreactive swelling undergoing further expansion over 1 week postinjury. These findings demonstrate the utility of the previously described immunocytochemical strategies for detecting reactive axonal change in brain-injured humans, particularly in the early posttraumatic course. More importantly, these methods also demonstrate in humans that reactive axonal change is not necessarily caused by traumatically induced tearing. PMID- 8440997 TI - Differential expression of the insulin-like growth factor II and transthyretin genes in the developing rat choroid plexus. AB - Choroid plexus (CP) development may depend on an inductive interaction between primordial CP epithelium and the overlying mesenchyme. Expression of the two CP epithelial-expressed genes, transthyretin (TTR) and insulin-like growth factor II (IGF-II), were studied by in situ hybridization in the developing rat. Transthyretin mRNA is expressed in abundance in the primordial CP epithelium prior to CP morphogenesis (e10-11) but IGF-II mRNA expression begins later (e13) and increases gradually as morphogenesis proceeds. In the CP stroma (mesenchyme), IGF-II mRNA is abundant prior to CP morphogenesis but decreases as embryogenesis proceeds and is absent in the adult. Our findings suggest that IGF-II may play an early paracrine and later autocrine role in CP development. A model is proposed in which IGF-II synthesized by mesenchyme serves as an inducing principle for CP epithelial differentiation. PMID- 8440998 TI - "Nature reveals herself to science". Memoirs of Kenneth Martin Earle, M.D., M.Sc. PMID- 8440999 TI - Pathogenesis of multiple sclerosis--the immune diathesis and the role of viruses. AB - Although the evidence of involvement of viruses in the pathogenesis of MS is largely circumstantial, the pattern of association is constant, with little evidence for direct viral infection of the CNS but with a consistent immune response to several common viruses. In parallel with these studies, epidemiological studies, while indicating genetic predisposition, favor an environmental pathogenetic factor and experimental models indicate that viruses can induce demyelination either by oligodendrolysis or by a variety of immune mechanisms with or without persistence in the CNS. In elucidating the pathogenesis of MS, the challenge is to understand the basis of the immune abnormalities, with intrathecal synthesis of viral antibodies and abnormal immune responses to some viruses, and to relate these to the MRI abnormalities which indicate periodic BBB breakdown. There is strong evidence that the breakdown is associated with inflammation. and that cytokines, particularly TNF, may play a role in demyelination. In conclusion, therefore, several factors are probably key in our understanding of MS. These include: (i) the genetic control of the immune system and its interaction with viral antigen; (ii) related effects on cerebral endothelium including cytokine and adhesion molecule regulation; and (iii) associated glial and axonal responses. Such an approach to the pathogenesis of MS may not identify a specific cause. It may, however, indicate that a pathological cascade can be "triggered" by several common viral infections and that therapy can be used to intervene at several points in the pathological response. PMID- 8441000 TI - Macaque ganglion cell responses to stimuli that elicit hyperacuity in man: detection of small displacements. AB - We measured responses of macaque ganglion cells as a function of contrast in a simple hyperacuity task, detection of displacement of an achromatic edge. Responses of ganglion cells of the magnocellular (MC) pathway were much more vigorous than those of cells of the parvocellular (PC) pathway. From the variability in the number of impulses in the response as compared with the distribution of impulses in maintained activity, it was possible to generate receiver operating characteristics for cells of the two pathways, and to predict individual cells' capability to detect a displacement with 75% probability. On comparing cell sensitivities to human psychophysical thresholds (75% probability of correct identification of displacement direction) at an equivalent retinal eccentricity (approximately 6 degrees), we found that one or two additional impulses in two MC pathway cells would suffice to support an ideal detector underlying psychophysical performance, at all contrast levels. Many more PC pathway cells would be required, especially at low contrasts. The much higher signal-to-noise ratio in the MC pathway relative to the PC pathway indicates that the MC pathway is likely to support this and other hyperacuity tasks. PMID- 8441001 TI - Replacement of lateral line sensory organs during tail regeneration in salamanders: identification of progenitor cells and analysis of leukocyte activity. AB - It has been proposed that supporting cells may be the progenitors of regenerated hair cells that contribute to recovery of hearing in birds, but regeneration is difficult to visualize in the ear, because it occurs deep in the skull. Hair cells and supporting cells that are comparable to those in the ear are present in lateral line neuromasts, and in axolotl salamanders these cells are accessible to microscopic observation in vivo. After amputation of a segment of the tail that contains neuromasts, cells from the posteriormost neuromast on the tail stump divide rapidly and form a migratory regenerative placode. The cells of the regenerative placode represent a lineage that eventually produces both hair cells and supporting cells in replacement neuromasts. We sought to identify the progenitors of the regenerative placode by using differential interference contrast microscopy combined with time-lapse video recording in living axolotl salamanders. In response to amputation, the mantle-type supporting cells at the posteroventral edge of the neuromast that is nearest to the wound increased their frequency of cell division, and gave rise to the first cells of the placode. The increase in mitotic activity of mantle-type supporting cells was accompanied by an unexplained decrease in the frequency of divisions in the same neuromast's population of internal supporting cells. The time-lapse records suggested that the changes in the mitotic activity of supporting cells might have been linked to the presence of phagocytic leukocytes in the vicinity of the neuromast that was nearest to the wound. Leukocytes were evenly distributed around control neuromasts, but during regeneration leukocyte activity increased significantly in the vicinity of the posterior half of the posteriormost neuromast. The redistribution of leukocytes occurred early in the regenerative response, but a causal role for the leukocytes has not been conclusively established. It is possible that the leukocytes could contribute to the formation of the regenerative placode at that location by breaking down the glycocalyx that ensheaths the outermost cells of the neuromast, or through the secretion of mitogenic growth factors. PMID- 8441002 TI - Modulation of dopamine efflux in the striatum following cholinergic stimulation of the substantia nigra in intact and pedunculopontine tegmental nucleus-lesioned rats. AB - The effects of microinjections of cholinergic agents into the substantia nigra pars compacta on dopamine (DA) efflux in the anterior dorsomedial striatum of urethane-anesthetized rats were investigated using in vivo chronoamperometry and intracerebral microdialysis techniques. A dose-dependent augmentation of DA efflux as evidenced by increases in the chronoamperometric signals was observed in the striatum following nigral microinjections of the cholinergic agonists nicotine or carbachol. Enhancing extracellular concentrations of ACh in the substantia nigra by intranigral infusions of the cholinesterase inhibitor neostigmine also resulted in an increase in the chronoamperometric signal corresponding to DA overflow in the striatum. These stimulatory effects of neostigmine on DA efflux in the striatum were confirmed using in vivo microdialysis. Compared to sham-operated control animals, quinolinic acid lesions of the pedunculopontine tegmental nucleus (PPTg) resulted in an attenuation of the stimulatory effects of intranigral neostigmine on DA efflux in the striatum. In contrast, these treatments resulted in an enhancement of striatal DA efflux in response to nigral infusions of the direct ACh receptor agonist nicotine. Combined, these data suggest that PPTg cholinergic neurons are indirectly involved in regulating the activity of the striatum by modulating the activity of DA neurons in the substantia nigra of the rat. PMID- 8441003 TI - Effect of SCN lesions on sleep in squirrel monkeys: evidence for opponent processes in sleep-wake regulation. AB - Sleep and wakefulness are governed by both the suprachiasmatic nuclei of the hypothalamus (SCN), and a sleep homeostatic process; however, the interaction of these control systems is not well understood. From rodent studies it has been assumed that the SCN promote neither wake nor sleep but gate the homeostatic sleep-promoting process. Yet in humans sleep tendency is lowest during the later waking hours of the day, and sleep duration can be predicted because of the precise circadian timing of waking. Thus in primates, the SCN could assure sleep wake cycle consolidation by actively promoting or facilitating wakefulness. To evaluate this hypothesis, we examined the sleep-wake and sleep-stage patterns of intact and SCN-lesioned (SCNx) squirrel monkeys maintained in constant light. This diurnal primate has consolidated sleep and wake patterns more similar to man than rodents. Sleep-wake, sleep stages, brain temperature, and drinking circadian rhythms were eliminated, and total sleep time was significantly increased (4.0 hr, P < 0.01) in SCNx monkeys. However, total times in deeper stages of non-rapid eye movement (non-REM; e.g., delta sleep) and REM sleep were not significantly affected by SCN lesions. Increased total sleep time was associated with a reduction in subjective day wake consolidation, as evidenced by substantially shorter wake bout lengths in SCNx monkeys (15 +/- 6 min) as compared to intact monkeys (223 +/- 10 min; P < 0.0001, ANOVA). These findings show that the SCN influence the regulation of daily total wake and sleep times, and implicate an alternative sleep-wake regulatory model in which an SCN-dependent process actively facilitates the initiation and maintenance of wakefulness and opposes homeostatic sleep tendency during the subjective day in diurnal primates. PMID- 8441004 TI - Neuropeptide Y mRNA and immunoreactivity in hypothalamic neuroendocrine neurons: effects of adrenalectomy and chronic osmotic stimulation. AB - Neuropeptide Y (NPY) coexists with vasopressin or oxytocin in magnocellular neurons of the hypothalamo-neurohypophysial tract. Using quantitative in situ hybridization histochemistry and immunohistochemistry, we have studied the effects of adrenalectomy and chronic osmotic stimulation, either alone or in combination, on NPY mRNA expression and NPY immunoreactivity in magnocellular neurons of the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, and arcuate nucleus (Arc). Adrenalectomy and chronic osmotic stimulation each increased NPY mRNA levels in magnocellular neurons of the PVN and SON, while the combination of both treatments had an additive effect. In the Arc, only the combination of adrenalectomy and chronic osmotic stimulation increased NPY mRNA levels. Chronic osmotic stimulation also resulted in a marked increase of NPY immunoreactive magnocellular perikarya in the PVN and SON. In contrast, adrenalectomy had only minor effects on the number of NPY-immunoreactive magnocellular PVN/SON perikarya. Neither chronic osmotic stimulation nor adrenalectomy affected the number of NPY-immunoreactive Arc perikarya. However, adrenalectomy decreased the number of NPY-immunoreactive nerve terminals in the external zone of the median eminence, while chronic osmotic stimulation increased the number of immunoreactive nerve fibers in the internal zone of the median eminence. The present study provides evidence that adrenalectomy and chronic osmotic stimulation can separately influence NPY gene transcription in magnocellular hypothalamo-neurohypophysial neurons, while only the combined effect of adrenalectomy and chronic osmotic stimulation increases NPY mRNA expression in neurons of the Arc. PMID- 8441005 TI - Dynamics of intracellular free calcium concentration in the presynaptic arbors of individual barnacle photoreceptors. AB - At photoreceptor synapses, transmitter release is continuous and graded. At this type of synapse, the control of presynaptic [Ca2+]i and calcium's role in releasing transmitter might be different than at terminals invaded by all-or-none action potentials. To examine this possibility, we measured the spatial and temporal changes of [Ca2+]i in response to depolarization of individual photoreceptor terminals of the barnacle Balanus nubilus, which had been injected with the Ca2+ indicator Fura-2. Depolarizing pulses produced voltage-dependent Ca2+ entry that was confined to the tips of the arbor where the release sites are located. At increasing distances from the tips, the rate of [Ca2+]i increase was slower and the peak [Ca2+]i occurred later, suggesting that Ca2+ entered the tips and diffused back into the larger processes of the arbor. Consistent with this result, a stable gradient of [Ca2+]i was observed at maintained depolarizations, with the highest values at the tips of the arbor. Removal of external Na+ did not affect the time course of Ca2+ decline in the terminal, indicating that Na+/Ca2+ exchange was not the primary mechanism for restoring [Ca2+]i to basal levels. Computer simulations, assuming only Ca2+ entry at the arbor's tips and diffusion of Ca2+ away from the entry site, qualitatively reproduced these observations. The threshold for Ca2+ entry was near -60 mV, and entry was maintained during prolonged depolarizations, in agreement with previous experiments showing that Ca2+ channels in the terminal region do not inactivate. The time course of the measured [Ca2+]i change in the terminal paralleled voltage changes due to a Ca(2+)-activated K+ conductance, which senses [Ca2+]i just under the membrane. This parallelism is expected since the release sites are located on processes of small-enough diameter to permit radial equilibration of [Ca2+]i within the time course of physiological voltage changes. Therefore, the optical measurements reflect the mean level of [Ca2+]i under the membrane. Whether this mean concentration is also the value at the sites that trigger exocytosis will depend on how close the Ca2+ channels are to these sites. PMID- 8441006 TI - Temporal filtering properties of midbrain neurons in an electric fish: implications for the function of dendritic spines. AB - Electrosensory neurons in the torus semicircularis (midbrain) of the weakly electric fish Eigenmannia vary considerably in their dendritic structure and responses to modulations of the amplitude of electric organ discharges. We investigated possible relations between these properties by recording intracellularly and labeling individual neurons while modulating stimulus amplitude over rates of approximately 2-20 Hz. Morphologically distinct cell types generally differed in their responses to these stimuli. The amplitude envelope of the stimulus was nicely reflected in fluctuations of the membrane potential of heavily spined neurons. The amplitude of these stimulus-related depolarizations decreased markedly as the stimulus modulation rate was increased. For aspiny or sparsely spined neurons, however, the amplitude of stimulus-related depolarizations either increased or remained constant over this range of modulation rates. In these cells, the amplitude envelope of the stimulus was not well represented in the membrane potential. Instead, fast EPSPs were observed that varied in number over time in accordance with the amplitude envelope of the stimulus. Aspiny neurons in the tectum also coded the amplitude envelope of stimuli with poor fidelity. The amplitude of stimulus-related depolarizations, however, decreased as the rate of modulation of stimulus amplitude was increased, consistent with the notion that tectal neurons receive afferent input from the spiny toral neurons. Spiny neurons appear, therefore, to act as low-pass filters of temporal information in sensory signals. Aspiny cells, however, code high temporal frequencies. These data support the hypothesis that dendritic spines contribute to the low-pass filtering of inputs to neurons. PMID- 8441007 TI - Sympathetic neurons expressing cholinergic properties are poised to allocate choline symmetrically between acetylcholine and the phosphatidylcholine generating pathway in growing neurites. AB - We have examined the question of how regenerating sympathetic neurons that are concomitantly induced to become cholinergic regulate choline allocation between ACh and the phospholipid synthetic pathway. The allocation of choline into ACh increased parabolically with time in culture, and by 3 weeks, cultures with neurites of approximately 6 mm length were incorporating over 85% of the choline locally in the neurites into four major metabolites: ACh, phosphorylcholine, cytidine diphosphocholine, and phosphatidylcholine. The near-equivalent distribution of labeled choline between intracellular choline, ACh, and phosphorylcholine was independent of time (5 min to 6 hr) and choline concentration (0.125-30 microM), phosphatidylcholine being the sole metabolite whose level in the neurites increased steadily with incubation time. Relative choline distribution into ACh and phosphorylcholine was unaltered even after a brief depolarizing prepulse, which caused a two- to fourfold enhancement in the total choline incorporated. These observations, allied with the similar half saturation constants and Vmax values of CAT and choline kinase for intracellular choline, suggest that growing sympathetic neurons are poised to allocate choline symmetrically between the synthesis of ACh and phosphatidylcholine in the neurites. When, however, the supply of choline was limited either by replacement of Na+ in the medium with N-methyl-D-glucamine, or by vesamicol, a 90-97% reduction in intracellular choline caused a similar decline in ACh levels but synthesis of metabolites of the phosphatidylcholine pathway was maintained unperturbed, as if no drug was present. We suggest that this can be accounted for by a 10-fold increase in choline kinase activity. Thus, growing sympathetic neurons that express cholinergic properties not only maintain their chief cellular phosphatidylcholine-synthesizing activity concomitantly with ACh synthesis in the neurites, but may also preserve phosphatidylcholine synthesis more effectively than ACh synthesis when the supply of choline is perturbed. Relinquishing ACh synthesis during growth may be one way of conserving and encouraging neurite regeneration. PMID- 8441008 TI - A PET study of visuospatial attention. AB - Positron emission tomography (PET) was used to identify the neural systems involved in shifting spatial attention to visual stimuli in the left or right visual field along foveofugal or foveocentric directions. Psychophysical evidence indicated that stimuli at validly cued locations were responded to faster than stimuli at invalidly cued locations. Reaction times to invalid probes were faster when they were presented in the same than in the opposite direction of an ongoing attention movement. PET evidence indicated that superior parietal and superior frontal cortex were more active when attention was shifted to peripheral locations than when maintained at the center of gaze. Both regions encoded the visual field and not the direction of an attention shift. In the right superior parietal lobe, two distinct responses were localized for attention to left and right visual field. Finally, the superior parietal region was active when peripheral locations were selected on the basis of cognitive or sensory cues independent of the execution of an overt response. The frontal region was active only when responses were made to stimuli at selected peripheral locations. These findings indicate that parietal and frontal regions control different aspects of spatial selection. The functional asymmetry in superior parietal cortex may be relevant for the pathophysiology of unilateral neglect. PMID- 8441009 TI - Visuospatial versus visuomotor activity in the premotor and prefrontal cortex of a primate. AB - When visuospatial stimuli instruct a limb movement, the stimulus can be said to have both sensory and sensorimotor aspects. We studied the premotor and prefrontal areas of a rhesus monkey in order to identify neuronal activity related to the motor (or instructional) aspects of such stimuli. A rhesus monkey chose limb-movement targets according to one of two rules: (1) visuospatial stimuli instructed and triggered a limb movement toward their locations or (2) identical stimuli triggered a movement toward a predetermined target regardless of their location. Gaze and head fixation assured that each stimulus appeared at a constant location in both retinocentric and craniocentric coordinates, as well as in allocentric space. The task required that the spatial location cued by certain stimuli had to be either remembered or attended after stimulus presentation and before movement. Thus, the visuospatial information presented under one rule differed from that presented under the other only in its motor (instructional) significance and not in its attentional, spatial, mnemonic, or strictly sensory aspects. We could thereby test and confirm the hypothesis that the motor significance of visuospatial cues should commonly affect neuronal activity in the premotor cortex, but less commonly do so in the prefrontal cortex. PMID- 8441010 TI - Gene expression of prohormone and proprotein convertases in the rat CNS: a comparative in situ hybridization analysis. AB - Posttranslational processing of proproteins and prohormones is an essential step in the formation of bioactive peptides, which is of particular importance in the nervous system. Following a long search for the enzymes responsible for protein precursor cleavage, a family of Kexin/subtilisin-like convertases known as PC1, PC2, and furin have recently been characterized in mammalian species. Their presence in endocrine and neuroendocrine tissues has been demonstrated. This study examines the mRNA distribution of these convertases in the rat CNS and compares their expression with the previously characterized processing enzymes carboxypeptidase E (CPE) and peptidylglycine alpha-amidating monooxygenase (PAM) using in situ hybridization histochemistry. Furin mRNA was ubiquitously distributed and detected both in neurons and non-neuronal tissue throughout the brain with a higher abundance in ependyma, the circumventricular organs, the islands of Calleja, hippocampus, and allocortex. The cellular localization of PC1 and PC2 was exclusively neuronal with highest concentrations in known neuropeptide-rich brain regions. In general, PC2 was more widely expressed than PC1 in the CNS, although many regional variations were detected. The identification of specific combinations of convertase expression together with CPE and PAM expression in neuropeptide-rich brain regions suggests that specific enzymatic pathways are involved in neuropeptide precursor processing, and that these specific combinations are responsible for region-specific differences of posttranslational processing. PMID- 8441011 TI - Role of substrate and calcium in neurite retraction of leech neurons following depolarization. AB - The aim of these experiments was to analyze how depolarization influences neurite outgrowth in leech neurons and what role the substrate and Ca2+ play in this response. Neurons in culture were exposed to 60 mM extracellular K+ for 30 min, which induced retraction of a subset of neurites growing on extracellular matrix substrate (ECM), a response comparable to that observed after electrical stimulation (Grumbacher-Reinert and Nicholls, 1992). After normal medium had been restored, the neurites continued to retract for about 1 hr to approximately 80% of the total starting neurite length. Retraction was reversible and regrowth began after the cells had been in normal medium for about 3 hr. Similar depolarization-induced neurite retraction was observed in both Retzius and anterior pagoda cells. Retraction was inhibited by raised extracellular Mg2+, suggesting a mechanism dependent on calcium. The effect of high K+ on neurite outgrowth was also influenced by the substrate on which the cells were plated. Cells plated on concanavalin A (ConA) did not retract but continued to extend processes during exposure to high K+. To understand the different behavior of cells grown on ECM and ConA, the morphology of growth cones was analyzed by scanning electron microscopy. The growth cones of cells grown on ECM and exposed to high K+ revealed retraction of lamellipodial and filopodial structures. On ConA, however, no differences were observed between growth cones of cells exposed to high K+ and those of control cells. These results demonstrate the importance of substrate molecules in the responses of growth cones to depolarization and therefore in the differentiation of neurons. PMID- 8441012 TI - Activity-dependent potentiation of recurrent inhibition: a mechanism for dynamic gain control in the siphon withdrawal reflex of Aplysia. AB - The siphon withdrawal response (SWR) of Aplysia supports several forms of learning that are under both excitatory and inhibitory control. Here we examine the role of interneuronal processing on the regulation of siphon responses, with an emphasis on the role of inhibition. We focus on the recurrent circuit formed by the excitatory interneuron L29 and the inhibitory interneuron L30, and show that this circuit provides a mechanism for use-dependent regulation of excitatory input onto siphon motor neurons. We utilized a reduced preparation in which input to the SWR circuit was elicited by taps applied to the siphon; tap-evoked EPSPs were measured in LFS siphon motor neurons. We first show that L29 is an important source of excitatory input to LFS motor neurons: voltage-clamp inactivation of a single L29 (out of five) results in a significant reduction of tap-evoked EPSPs. Next, we demonstrate that direct intracellular activation of L29, surprisingly, produces transient inhibition of evoked input to motor neurons that lasts up to 40 sec. We then provide several lines of evidence that the mechanism of L29 induced inhibition is through the recruitment and potentiation of recurrent inhibition from L30: (1) L29 activation results in reduced tap-evoked responses of other (nonactivated) L29s; (2) direct activation of L30 mimics the inhibitory effects produced by L29 activation (LFS neurons receive no direct synaptic input from L30); and (3) the L30 IPSP is significantly potentiated as a result of its own activity, whether produced directly (by L30 activation) or indirectly (through L29 activation). This IPSP potentiation has the same time course as L29 induced inhibition of motor neuron responses. Thus activity-dependent potentiation of L30 transmission can inhibit motor neuron responses, in part through inactivation of the L29 interneuronal pool. Finally, we propose that L29 L30 interactions provide a mechanism for dynamic gain control in the SWR. PMID- 8441013 TI - Coexpression of mRNAs for NGF, BDNF, and NT-3 in the cardiovascular system of the pre- and postnatal rat. AB - The expression of NGF, brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) mRNAs was examined in whole rat embryos and in the heart and great vessels of postnatal and adult rats, using in situ hybridization of cRNA probes. The patterns of expression were correlated with innervation patterns as revealed by immunostaining for neural cell adhesion molecule (NCAM) and with the HNK-1 antibody, which demonstrates derivatives of the neural crest. The patterns of neurotrophin mRNA localization were different from those of mRNAs for the low molecular-weight NGF receptor. Hybridization indicating the presence of mRNAs for all three neurotrophins is particularly prominent within the tunica media of the aorta, pulmonary, and other major elastic arteries of the thorax and abdomen and is first observed on embryonic day 13 (E13) when innervation is being established and rises to maximum by E15. In the fetus, there is little or no detectable expression in the CNS or PNS. NT-3 expression in the vessels is relatively constant and high from embryonic to adult stages, while levels of BDNF increase and those of NGF decrease over the same time course. During the fetal period, hybridization in the heart is absent. In the postnatal period, additional label becomes detectable in the coronary arteries but not in the walls of the atria or ventricles, other than at the base of the aorta and pulmonary trunk.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441014 TI - Excitation of rat locus coeruleus neurons by adenosine 5'-triphosphate: ionic mechanism and receptor characterization. AB - ATP and several congeners were applied to locus coeruleus neurons in slices cut from rat pons. Whole-cell recording of membrane current showed that ATP caused an inward current at -60 mV. Effective concentrations (applied by superfusion) were 3-300 microM, and the peak current was about 150 pA at -60 mV. 2 Methylthioadenosine 5'-triphosphate was slightly more potent than ATP, adenosine 5'-diphosphate was about equipotent with ATP, alpha,beta-methylene adenosine 5' triphosphate was slightly less potent than ATP, and beta,gamma'-methylene adenosine 5'-triphosphate and adenosine 5'-monophosphate had little or no effect. Adenosine (100 microM) caused small outward currents (40 pA). By changing the ionic composition of the pipette and extracellular solution, it was shown that the inward current resulted from both an increase in conductance to sodium ions and a reduction in conductance to potassium ions. It is concluded that rat locus coeruleus neurons express P2 purinoceptors, activation of which depolarizes the cells predominantly by increasing a conductance that allows sodium ions to enter the cell. PMID- 8441015 TI - Responses of monkey dopamine neurons to reward and conditioned stimuli during successive steps of learning a delayed response task. AB - The present investigation had two aims: (1) to study responses of dopamine neurons to stimuli with attentional and motivational significance during several steps of learning a behavioral task, and (2) to study the activity of dopamine neurons during the performance of cognitive tasks known to be impaired after lesions of these neurons. Monkeys that had previously learned a simple reaction time task were trained to perform a spatial delayed response task via two intermediate tasks. During the learning of each new task, a total of 25% of 76 dopamine neurons showed phasic responses to the delivery of primary liquid reward, whereas only 9% of 163 neurons responded to this event once task performance was established. This produced an average population response during but not after learning of each task. Reward responses during learning were significantly more numerous and pronounced in area A10, as compared to areas A8 and A9. Dopamine neurons also showed phasic responses to the two conditioned stimuli. These were the instruction cue, which was the first stimulus in each trial and indicated the target of the upcoming arm movement (58% of 76 neurons during and 44% of 163 neurons after learning), and the trigger stimulus, which was a conditioned incentive stimulus predicting reward and eliciting a saccadic eye movement and an arm reaching movement (38% of neurons during and 40% after learning). None of the dopamine neurons showed sustained activity in the delay between the instruction and trigger stimuli that would resemble the activity of neurons in dopamine terminal areas, such as the striatum and frontal cortex. Thus, dopamine neurons respond phasically to alerting external stimuli with behavioral significance whose detection is crucial for learning and performing delayed response tasks. The lack of sustained activity suggests that dopamine neurons do not encode representational processes, such as working memory, expectation of external stimuli or reward, or preparation of movement. Rather, dopamine neurons are involved with transient changes of impulse activity in basic attentional and motivational processes underlying learning and cognitive behavior. PMID- 8441016 TI - Corticosteroids regulate brain hippocampal 5-HT1A receptor mRNA expression. AB - Using in situ hybridization techniques, the expression of 5-HT1A receptor mRNA was measured within the hippocampal formation after bilateral adrenalectomy (ADX). After 24 hr ADX, 5-HT1A receptor mRNA expression was significantly increased in all hippocampal subfields in ADX animals relative to sham-operated controls (SHAM). The magnitude of the increase was most pronounced within CA2 (127%) and CA3/4 (94%)-subfields of dorsal hippocampus, intermediate in the dentate gyrus (73%), and least within CA1 (60%). Administration of exogenous corticosterone (CORT) at the time of ADX maintained the level of 5-HT1A receptor mRNA expression within the range of SHAM animals. In vitro receptor autoradiographic analysis of 5-HT1A receptors in adjacent sections from the same animals indicated a simultaneous increase in 5-HT1A binding throughout the hippocampus in response to ADX. 5-HT1A binding increased to a similar extent (approximately 30%) in CA subfields and dentate gyrus but remained within SHAM levels in CORT-replaced animals. 5-HT1A receptor mRNA levels were also increased in hippocampal subregions of 1 week ADX animals relative to SHAM animals. Within both CA1 and CA2 subfields, the increments were approximately double those observed after 1 d ADX. 5-HT1A receptor binding was increased in every hippocampal subfield to a similar extent as that observed after 1 d ADX. Increases in both 5-HT1A receptor mRNA expression and 5-HT1A receptor binding were preventable by administration of exogenous CORT at the time of ADX. Hippocampal 5-HT1C receptor mRNA and D1 receptor mRNA expression were not significantly altered by either acute or chronic ADX treatment. These data indicate that adrenal steroids may selectively regulate hippocampal 5-HT1A receptors at the level of 5-HT1A receptor mRNA expression. PMID- 8441017 TI - Combination-sensitive neurons in the primary auditory cortex of the mustached bat. AB - In the mustached bat, Pteronotus parnellii, neurons in the primary auditory cortex (AI) have been thought to respond primarily to single frequencies, as in other mammals. However, neurons in the Doppler-shifted constant-frequency (DSCF) area, a part of the mustached bat's AI that contains an overrepresentation of the prominent CF2 component of the biosonar signal, were found to show facilitative responses to combinations of different frequencies in the pulse and echo. The essential components for facilitation were the pulse FM1 and the echo CF2. The FM1-CF2 facilitation was sensitive to echo delays, indicating that DSCF neurons respond better to targets within particular ranges. On average, the longest discriminable echo delay, based on increased impulse counts due to facilitation, corresponded to a target range of 4.3 m, and the most discriminable delay corresponded to a target 3.6 m distant. Since mustached bats first show a behavioral response to a target at a distance of 3-4 m, DSCF neurons are suited to signal the presence of an insect within this behaviorally important range. DSCF neurons were broadly tuned to echo delay, with the average minimum discriminable echo delay corresponding to a target range of 1.9 m, and the delay tuning of the neurons followed (tracked) changes in pulse duration, indicating that facilitation occurs during much of the approach phase of insect pursuit when target characterization is presumably occurring. These results show that AI neurons in the mustached bat are specialized to respond to complex, behaviorally relevant stimuli during the search and approach phases of insect pursuit. PMID- 8441018 TI - Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types. AB - Proton nuclear magnetic resonance (1H NMR) spectroscopy is a noninvasive technique that can provide information on a wide range of metabolites. Marked abnormalities of 1H NMR brain spectra have been reported in patients with neurological disorders, but their neurochemical implications may be difficult to appreciate because NMR data are obtained from heterogeneous tissue regions composed of several cell populations. The purpose of this study was to examine the 1H NMR profile of major neural cell types. This information may be helpful in understanding the metabolic abnormalities detected by 1H NMR spectroscopy. Extracts of cultured cerebellar granule neurons, cortical astrocytes, oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells, oligodendrocytes, and meningeal cells were analyzed. The purity of the cultured cells was > 95% with all the cell lineages, except for neurons (approximately 90%). Although several constituents (creatine, choline-containing compounds, lactate, acetate, succinate, alanine, glutamate) were ubiquitously detectable with 1H NMR, each cell type had distinctive qualitative and/or quantitative features. Our most unexpected finding was a large amount of N-acetyl-aspartate (NAA) in O-2A progenitors. This compound, consistently detected by 1H NMR in vivo, was previously thought to ne present only in neurons. The finding that meningeal cells have an alanine:creatine ratio three to four times higher than astrocytes, neurons, or oligodendrocytes is in agreement with observations that meningiomas express a higher alanine:creatine ratio than gliomas. The data suggest that each individual cell type has a characteristic metabolic pattern that can be discriminated by 1H NMR, even by looking at only a few metabolites (e.g., NAA, glycine, beta-hydroxybutyrate).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441019 TI - Ban on enriched uranium exports intended against bomb builders also affects radiopharmaceutical makers. PMID- 8441020 TI - NRC chairman's mandate: patient "follow-up'. PMID- 8441021 TI - Next hurdle for radiolabeled antibodies: acceptance by medical insurers. PMID- 8441022 TI - Lines from the president: dispelling the confusion about radiation safety in medicine. PMID- 8441023 TI - The influence of plasma glucose levels on fluorine-18-fluorodeoxyglucose uptake in bronchial carcinomas. AB - PET studies with 2-18F-fluorodeoxyglucose (FDG) were carried out in 15 patients with bronchial carcinomas, first under fasting conditions and then 2 days later during intravenous infusion of a 20% glucose solution which raised the plasma glucose level from 84.6 +/- 14.7 to 168.3 +/- 23.6 mg/100 ml (n = 15, p < 0.001). Tumor metabolism was quantified by the dose absorption ratio (DAR) of FDG uptake [DAR = tissue concentration/(injected dose/body weight)] and also by the rate of glucose consumption (MR) as measured by the Patlak graphical approach in 12 patients. The DAR decreased from 5.07 +/- 1.89 under fasting conditions to 2.84 +/- 0.97 (-41.8% +/- 15%, n = 15, p < 0.001) during glucose infusion, while the MR remained constant (4.71 +/- 2.38 mg/100 ml/min versus 4.96 +/- 2.46 mg/100 ml/min, n = 12, ns). Correction of the DAR data by plasma glucose level eliminated the significant difference between the fasting and glucose load [4.24 +/- 1.59 versus 4.70 +/- 1.45 (n = 15, ns)], but considerable changes in individual patients remained. These data indicate that the DAR of FDG uptake in bronchial carcinomas is influenced significantly by plasma glucose levels. Dynamic quantification of glucose metabolism using the Patlak approach is less dependent on the plasma glucose level and appears advantageous when high reproducibility is needed. PMID- 8441024 TI - Measurement of regional cerebral glucose utilization with fluorine-18-FDG and PET in heterogeneous tissues: theoretical considerations and practical procedure. AB - Functional tissue heterogeneity, i.e., inclusion of tissues with different rates of blood flow and metabolism within a single region of interest, is an unavoidable problem with PET. Errors in determination of regional cerebral glucose utilization (rCMRglc) with [18F]FDG have resulted from the currently used simplifying assumption that all regions examined are homogeneous. We have established an optimal, yet practical procedure to minimize errors due to tissue heterogeneity in determination of rCMRglc. Effects of applying the three-rate constant kinetic model designed for homogeneous tissues with both dynamic and single-scan procedures and the Patlak plot were evaluated in normal subjects in experimental periods up to 120 min following tracer injection. The procedure with a single scan carried out any time within the interval between 60 and 120 min following tracer injection, combined with population average rate constants determined over a 120-min period, was found to be optimal for quantitative rCMRglc studies. PMID- 8441025 TI - The underestimation of segmental defect size in radionuclide lung scanning. AB - Criteria used to place ventilation-perfusion lung scans into categories with different probabilities for pulmonary embolism depend largely on the size and anatomical distribution of defects recognized. These criteria assume that actual segmental defects appear segmental on the lung scan. This study examined the accuracy with which four experienced observers were able to estimate the size of defects of known anatomical location and size, using images of segmental defects in ventilation produced with a bronchoscopic technique and 81mKr. Of the 24 segmental defects produced in this study, 17% were interpreted as being < 25% of a segment; 23% were interpreted as being 25%-50% of a segment; 17% were interpreted as 50%-75% of a segment; 40% were interpreted as being 75%-100% of a segment and 4% were interpreted as being > 100% of a segment. Intra- and interobserver agreement as assessed by the Kappa statistic varied with the number of size categories used but was generally poor. Underestimation of defect size observed in this study may explain why many patients with pulmonary embolism do not have high probability scans. We conclude that the subjective impression of the size of a defect on a lung scan is an unreliable indication of a defect's true segmental or subsegmental nature and that scoring systems based on these criteria should be viewed with caution. PMID- 8441026 TI - Improved evaluation of technetium-99m-red blood cell SPECT in hemangioma of the liver. AB - This paper reports the results of a prospective study carried out to evaluate a new reading method of tomographic 99mTc red blood cell (RBC) imaging in liver hemangiomas. For this purpose, assessment of planar imaging and conventional, static 99mTc-RBC SPECT presentation (x-ray type film) (Method 1) was compared to a dynamic three-view display of SPECT slices (Method 2) in 21 patients with 56 hemangiomas and 18 patients with malignant liver lesions. Of the 56 hemangiomas, 47 were diagnosed by US, 6 by CT and 56 by MRI. Twenty-nine (52%) hemangiomas were detected by planar scintigraphy and 38 (68%) by SPECT Method 1, whereas 53 (95%) were visualized by SPECT Method 2. Comparing Methods 1 and 2 in hemangiomas < or = 1.0 cm, 1.1-2.0 cm and 2.1-3.0 cm in diameter, Method 2 improved sensitivity from 18% to 82%, 50% to 93% and 82% to 100%, respectively. The smallest hemangioma detected with Method 2 was 0.5 cm in diameter; with Method 1, 0.9 cm; and with planar imaging, 1.0 cm. As assessed by evaluation of the metastases and carcinomas, the specificity for hemangioma was 100%, independent of the method applied, resulting in a positive predictive value of 100%. This study suggests that evaluation of dynamically displayed 99mTc-RBC SPECT studies is superior to conventional reading of static display and comparable to MRI in liver hemangioma > or = 1 cm. Therefore, this approach is suggested as an alternative to MRI for confirming the diagnosis of liver hemangioma > or = 1 cm if planar imaging is negative. This option is available with most modern computer software systems and saves additional disbursement. PMID- 8441027 TI - Prospective study of magnetic resonance imaging and SPECT bone scans in renal allograft recipients: evidence for a self-limited subclinical abnormality of the hip. AB - We recently reported that typical abnormalities of avascular necrosis (AVN) in magnetic resonance images (MRI) of the hips of asymptomatic renal transplant recipients whose plain radiographs are normal may improve spontaneously and even disappear completely. We present the results of serial bone scans, most of which were performed with single-photon emission computed tomography obtained over periods as long as 24 mo after transplantation in 72 of these patients. Three paired imaging studies (i.e., MR and bone scan performed within 30 days of each other) were available for each of these patients. In three patients, both the MR images and the bone scans showed changes consistent with bilateral AVN within 4 mo after transplantation. All three patients developed hip pain which was bilateral in two and unilateral in one. Two patients (three hips) required surgical intervention at which time AVN was found on pathologic examination of all three hips. None of the remaining 69 patients developed hip pain during the study. However, in nine patients whose MR studies were consistently normal, at least one bone scan was abnormal (13 hips). The presence of AVN was pathologically confirmed in each of the hips subjected to surgery. Where the imaging findings were identical to those in the asymptomatic patients as well as those in whom the imaging abnormality regressed, we suggest that the subclinical imaging abnormalities represent mild AVN, which is reversible in some cases. Since the process was identified in 10 hips by MRI and in 13 hips by bone scan, both studies are needed to detect subclinical AVN. This may be important if treatment of subclinical disease is clearly shown to prevent progression to symptomatic AVN. PMID- 8441028 TI - Influence of dose selection on absorbed dose profiles in radioiodine treatment of diffuse toxic goiters in patients receiving or not receiving carbimazole. AB - We retrospectively reviewed the records of 224 patients with diffuse goiters treated with radioiodine, half of which received carbimazole. In all the cases, we carefully monitored the calculation of dosage. A lower percentage of early hypothyroidism but a higher failure rate was observed in the carbimazole subgroup. Nevertheless, after one year, a constant (4.5%) incremental rate of hypothyroidism was found regardless of carbimazole administration. Since we were able to precisely estimate the absorbed doses in our series, we evaluated by simulation the dosimetric profiles of nine methods of dose selection (MDS). These MDS were calibrated in such a way that the same threshold value of absorbed dose would always be reached at the thyroid level. We showed that the more elaborate the MDS, the more accurate the irradiation at the thyroid level and the lower the radiation dose administered. In patients not receiving carbimazole, a rapid MDS using modified early uptake measurements to predict the 24-hr actual value was found to be advisable. With patients receiving carbimazole and if a goal is to delay the occurrence of hypothyroidism, we advise MDS based on either a 48-hr uptake or on the calculation of the individual half-life. PMID- 8441029 TI - Clinical outcome of cardiac patients with negative thallium-201 SPECT and positive rubidium-82 PET myocardial perfusion imaging. AB - In a previous comparison of 202 consecutive patients who underwent myocardial perfusion imaging with both 201Tl SPECT and 82Rb PET, 27 patients were identified as having true-positive 82Rb images, but false-negative 201Tl images. The purpose of this report is to determine the effect of correct image interpretation of coronary artery disease on the final management of those patients and compare it to the previous management scheme wherein a negative image was usually accepted as the end point unless clinical symptoms dictated otherwise. A follow-up study of the clinical course and outcome of these studies showed that 63% (17/27) of the patients with a true-positive 82Rb PET image were recommended for revascularization procedures. It is doubtful that this majority of patients would have received either surgical or interventional management based on the false negative 201Tl SPECT procedure alone. PMID- 8441030 TI - Measurement of PDT-induced hypoxia in Dunning prostate tumors by iodine-123 iodoazomycin arabinoside. AB - Photodynamic therapy (PDT) is known to produce vascular damage in solid tumors resulting in secondary ischemia and tumor cell death from hypoxia. The oxygenation status of both non-treated and PDT-treated Dunning R3327-AT prostate tumors growing in Fischer X Copenhagen rats was investigated with the novel hypoxic marker, 123I-iodoazomycin arabinoside (IAZA). Both qualitative and quantitative data from planar scintigraphy of anesthetized tumor-bearing rats showed increased retention of 123I-IAZA in tumors treated with PDT. Tumor perfusion in the same tumors was measured with 99mTc-hexamethylpropyleneamine oxime (HM-PAO). Region of interest analyses revealed an inverse correlation between tumor hypoxia measured by 123I-IAZA and tumor perfusion as measured by 99mTc-HMPAO (coefficient of correlation, r = -0.72). Planar images of 2-mm frozen sections from a large tumor showed 123I-IAZA selectively retained in the region that had been treated with PDT. This and other iodinated azomycin nucleosides, labeled with 123I, show promise for monitoring tumor oxygenation status non invasively and, in particular, for monitoring the effectiveness of interstitial PDT treatments where perfusion shutdown is a major mechanism of tumor response. PMID- 8441031 TI - Second generation hypoxia imaging agents. PMID- 8441032 TI - Does FDG uptake measure proliferative activity of human cancer cells? In vitro comparison with DNA flow cytometry and tritiated thymidine uptake. AB - The relationship between 3H-2-fluoro-2-deoxy-D-glucose (FDG) uptake and the proliferative rate of a human ovarian adenocarcinoma cell line (HTB77IP3) was examined in vitro. HTB77IP3 cells were plated and allowed to grow through lag, exponential and plateau phases. Proliferative rate assessed by DNA flow cytometry and 3H-thymidine incorporation was highest in the lag phase and fell significantly as the cells progressed from the exponential through plateau phases. By DNA flow cytometry, the proliferation index (% of S+G2/M phase cells) fell from 65% to 23%. Thymidine uptake per cell also declined, by 82%, from lag to plateau phase. By contrast, 3H-FDG uptake per cell was largely unchanged as the cells progressed through the cell growth cycle. Total 3H-FDG uptake was strongly correlated with the number of viable cancer cells present (r = 0.957). Total thymidine uptake, however, substantially underestimated the number of viable cancer cells present. These in vitro differences in tracer uptake suggest that in this adenocarcinoma cell line, FDG measures a substantially different parameter (viable cell number) than thymidine (proliferative rate) and that these differences may result in disparate findings on PET imaging of cancers using these two tracers. Our data for this in vitro system indicate that FDG uptake does not relate to the proliferative activity of cancer cells. However, FDG uptake is strongly related to the number of viable tumor cells. PMID- 8441033 TI - FDG accumulation in tumor tissue. PMID- 8441034 TI - Modeling and dosimetry of monoclonal antibody M195 (anti-CD33) in acute myelogenous leukemia. AB - Individual patient response to radioimmunotherapy is influenced by each patient's tumor burden, antibody clearance kinetics and the antibody-antigen interaction. In hematologic malignancies, wherein antibody access to tumor-cell associated antigen is rapid, mathematical modeling may provide a quantitative basis for assessing the impact of patient variability on a particular therapeutic protocol. Compartmental modeling analysis of antibody pharmacokinetics from a Phase I trial of 131I-labeled monoclonal antibody, M195 (anti-CD33), was used to estimate tumor burden in cases of acute myelogenous leukemia and the absorbed dose in liver, spleen and red marrow. The suitability of a nonlinear, two-compartment model for simulating M195 distribution in leukemia patients was evaluated by comparing model predictions with patient measurements. The results demonstrate that for directly accessible, hematologically distributed tumor cells, a two-compartment model fits observed patient biodistribution data and may provide information regarding both total tumor burden and tumor burden in the liver, spleen and red marrow. The model also provides biodistribution information for absorbed dose calculations to tissues that are not directly sampled. Such information is important in determining the optimum therapeutic dose of radiolabeled antibody for a given patient. PMID- 8441036 TI - Sampling requirements for dynamic cardiac PET studies using image-derived input functions. AB - The utilization of image-derived input functions is becoming common in quantitative PET studies of the heart. Consequently, imaging protocols must be designed to sample both blood and tissue concentrations adequately. Most clinical imaging protocols consist of a series of short initial scans to measure the rapid change in blood and tissue tracer concentration levels, followed by scans of gradually increasing length. The number of initial short scans must be matched to the shape of the input function. In this paper, noise-free simulation studies were performed to evaluate the effect of temporal sampling on estimates of the parameters of a two-compartment kinetic model. In addition, the consequences of varying tracer infusion length and timing were studied. The kinetic model parameters' bias decreased when infusion times were lengthened or sampling rates increased. Our results indicated that tracer infusions of 30 sec were best suited for these studies. Two currently employed clinical imaging protocols were then optimized for use with this infusion scheme. Ten initial scans with durations of 10 sec, or twenty of 5 sec length produced unbiased estimates of kinetic model parameters that describe myocardial physiology. Noisy simulations with the equivalent of one million events confirmed these results. PMID- 8441035 TI - Protein kinase C imaging using carbon-11-labeled phorbol esters: 12-deoxyphorbol 13-isobutyrate-20-[1-11C]butyrate as the potential ligand for positron emission tomography. AB - Protein kinase C plays a crucial role in signal transduction for a variety of biologically active substances which activates cellular functions and their proliferation. The actions are closely related to both normal and abnormal functions in the nervous system. Tumor-promoting phorbol esters can substitute for diacylglycerols which are important ligands that bind to protein kinase C. Three typical phorbol esters, phorbol 13-[1-11C]butyrate, phorbol 12,13-[1 11C]dibutyrate and 12-deoxyphorbol 13-isobutyrate-20-[1-11C]butyrate, were synthesized by using [11C]ethylketene with a high specific activity (186GBq/mumol). Their in vivo autoradiograms demonstrated a heterogenous distribution in rat brain. 12-deoxyphorbol 13-isobutyrate-20-[1-11C]butyrate was particularly suited for in vivo use due to its nontumor-promoting activity and its ready permeability to the blood-brain barrier. High optical density was observed in the cortex, amygdala and hippocampus. The in vivo binding properties of this compound to protein kinase C were confirmed by in vivo displacement studies with unlabeled 12-deoxyphorbol 13-isobutyrate-20-butyrate and unlabeled phorbol 12,13-dibutyrate. This suggests that 12-deoxyphorbol 13-isobutyrate-20-[1 11C] butyrate has a specific binding affinity for protein kinase C. PMID- 8441037 TI - A general, extracorporeal immunoadsorption method to increase the tumor-to-normal tissue ratio in radioimmunoimaging and radioimmunotherapy. AB - The aim of this study was to investigate a new extracorporeal immunoadsorption method to improve tumor-to-normal tissue ratios in radioimmunoimaging (RII) and radioimmunotherapy (RIT). We have developed and investigated a general method using biotinylated antibodies and an agarose-avidin column for extracorporeal immunoadsorption. The studies were made in an animal model and extracorporeal immunoadsorption (ECIA) was performed 24 or 48 hr after the injection of 125I labeled biotinylated antibodies. In athymic rats, heterotransplanted with human malignant melanoma, 90%-95% of the circulating activity was removed with ECIA. The tumor-to-normal tissue ratios at 24 hr was increased 4 times (from 1.2 to 5.1) in the liver, 2.5 times (0.7 to 1.8) in the lung, 4 times (1 to 4) in the kidneys and 4 times (1.4 to 5) in the bone marrow. Whole body activity was reduced by 40%-50%. Tumor-to-organ ratios at 48 hr were increased 3.5 times (from 1.5 to 5.2) in the liver, 2 times (0.9 to 1.7) in the lung, 3 times (1.3 to 3.8) in the kidneys and 4 times (1.4 to 5.5) in the bone marrow. Whole body activity was reduced by 35% when ECIA was performed 48 hr after injection. This study proves that an important reduction in background activity, and thereby an improvement in the tumor-to-background ratio, can be achieved by using this generally applicable, biotin-avidin ECIA method. For RII, the improved ratio increases the possibilities of detecting tumors and metastases in blood-rich organs. For RIT, the procedure may lead to a decreased absorbed dose to bone marrow and other critical organs. PMID- 8441038 TI - Enthesopathy of the patellar tendon insertion associated with isotretinoin therapy. AB - A 99mTc-MDP bone scan performed on a 34-yr-old female for suspected osteomyelitis of the proximal tibia revealed focally increased activity in both tibial tuberosities due to enthesopathies secondary to chronic isotretinoin therapy. Physicians should be aware that isotretinoin therapy can cause abnormal bone scans and not mistake these abnormalities for other diseases such as osteomyelitis. Second, bone scans may be helpful in diagnosing and following isotretinoin bone toxicity. PMID- 8441039 TI - Gallium-67-citrate and bone scintigraphy in disseminated North American blastomycosis. AB - We present a patient with North American blastomycosis involving lung and bone. Chest radiographs and CT scan showed a mass in the lung. Bone scintigraphy detected a photon-deficient area in the sternum and 67Ga SPECT showed uptake in the right upper lung and in the sternum. A diagnostic thoracotomy and needle biopsy from the sternal lesion revealed granulomatous infection due to Blastomyces dermatitidis. After 3 mo of antifungal therapy, the follow-up 67Ga study showed no evidence of the original lesions but demonstrated a new, asymptomatic, unsuspected lesion in the left infraspinatous muscle. This case illustrates that North American blastomycosis should be included in the differential diagnosis in cases of atypical pulmonary disease with bone involvement, even in geographic regions that are not considered endemic for this microorganism. Gallium-67 and bone scintigraphy may be useful in determining the extent of dissemination, in detecting occult lesions and in the follow-up of response to therapy. PMID- 8441040 TI - Open bronchial stump post-pneumonectomy: findings on xenon-133 ventilation imaging. AB - A 67-yr-old male status post right pneumonectomy for non-small cell lung cancer who later developed an open right bronchial stump underwent a ventilation perfusion lung scan because of episodes of recurrent dyspnea suspected to be due to pulmonary embolism. Xenon-133 ventilation images showed both rapid entry into and later washout of activity from the air-filled portion of the right thoracic cavity. A wide-open bronchial stump, documented both at bronchoscopy and later autopsy, allowed the xenon gas to freely wash out from the thoracic cavity, resulting in a different imaging pattern than for a typical bronchopleural fistula, which is usually characterized by prolonged trapping of radioactive gas within the pleural space. PMID- 8441041 TI - Unusual scintigraphic findings in a thyroid adenoma. AB - Thallium imaging is increasingly being used to evaluate the thyroid. Uptake patterns of 201Tl in benign and malignant thyroid nodules have been described. Thallium localizes all thyroid tissue with possibly different rates of washout in benign and malignant nodules. This case demonstrates a follicular adenoma presenting 123I as a clinically palpable nodule with nonvisualization of the remainder of the thyroid gland consistent with the diagnosis of an autonomously hyperfunctioning module. Subsequent thallium scanning revealed a complete reversal of tracer distribution with lack of uptake of 201Tl in the nodule while the rest of the gland showed normal thallium accumulation. Surgical excision of the nodule demonstrated follicular adenoma. PMID- 8441042 TI - The bacterial endotoxin test in the PET facility. AB - A method by which the gel-clot Limulus amebocyte lysate test may be performed in 20 rather than 60 min with sufficient sensitivity to satisfy the needs of the nuclear medicine or positron emission tomography laboratories has been developed and validated for use as a substitute for the Bacterial Endotoxin Test described in the United States Pharmacopeia, 22nd revision. Using this method, results may be obtained from the test prior to the human administration of radiopharmaceuticals without extensive loss of activity and with increased safety when compared to tests performed after administration. Additionally, studies on the shelf-lives of the reagents used in the test were conducted. When refrigerated between use, control standard endotoxin dilutions of 5 EU/ml or greater may be used for at least 1 mo after preparation and reconstituted lysate retains its labeled sensitivity for at least 10 days, considerably longer than the manufacturer's stated shelf-lives. PMID- 8441043 TI - A stationary hemispherical SPECT imager for three-dimensional brain imaging. AB - A completely stationary, hemispherical-coded aperture SPECT imaging system was designed to produce three-dimensional images of the brain. The system consisted of a hemispherical multiple-pinhole coded aperture and 20 small (100 x 100 mm crystal area) digital gamma cameras. Reconstructions and measured performance specifications from two laboratory versions of the imager are presented. The reconstructed field of view of these systems was an ellipsoidal region with semi diameters of 100 x 100 x 50 mm. The reconstructed spatial resolution for a point source in air at the center of this field was found to be 4.8 mm FWHM and the corresponding system sensitivity was 36 cps/microCi. An analysis using an ideal observer model indicated that the multiplexed projection data suffered a 21% degradation relative to similar, but nonmultiplexed SPECT data. Therefore, by this measure, the effective sensitivity of the brain imager was 79% of the measured value. PMID- 8441044 TI - Recovery of the human striatal signal in a slice oriented positron emission tomograph. AB - The human striatum is small enough for partial volume effects to be important when imaged in positron tomographs with slice widths 10 mm or greater. The combination of interslice distance and slice width in such tomographs results in an axial undersampling of the striatal activity which introduces the additional problem of variation of axial recovery as a function of position of the striatum along the tomograph axis. Using striatal phantoms, we have developed a method that corrects the recovered striatal signal to a maximum value equivalent to that measured when the object is centered with respect to a slice. This makes the recovery independent of the axial position of the striatum. The method also provides an estimate of the total striatal activity by integrating the axial image intensity distribution along the tomograph axis. The method is able to detect and correct for relative axial tilt of the left and right striatum. We applied it to 26 human [18F]-6-L-fluorodopa scans and obtained an average uptake rate constant k value of 0.25 +/- 0.05 ml/min/striatum and a left to right k value percentage asymmetry of 0.1% +/- 6.3%. PMID- 8441045 TI - A new graphic plot analysis for cerebral blood flow and partition coefficient with iodine-123-iodoamphetamine and dynamic SPECT validation studies using oxygen 15-water and PET. AB - To estimate regional cerebral blood flow (rCBF) and brain-blood partition coefficient (lambda) using a dynamic measurement, a new graphic plot analysis is proposed. By assuming a two-compartment model for tracer kinetics, we derived the linear relationship as Y(t) = K1 - k2 X(t), where Y(t) is the ratio of brain tissue activity-to-time-integrated arterial blood activity and X(t) is the ratio of time-integrated brain tissue activity-to-time-integrated arterial blood activity. A plot of Y(t) against X(t) yields a straight line and the y- and x intercept of the regression line represent rCBF (K1) and lambda, respectively. The slope is a washout constant (-k2). This method was applied to 14 subjects with N-isopropyl-p-iodine-123 iodoamphetamine ([123I]IMP). The mean values of K1 and lambda for normal subjects were 41.3 +/- 6.7 ml/100 g/min and 29.6 +/- 6.5 ml/g, respectively, in the gray matter. A comparative study with positron emission tomography (PET) using an H2(15)O autoradiographic method revealed good correlation between IMP K1 and PET rCBF [r = 0.822; K1 = 0.842 rCBF + 0.030 (ml/g/min)]. The values of K1 using the graphical method were in excellent agreement with those using a nonlinear least-squares fitting technique (r = 0.992 for K1; r = 0.941 for lambda). The estimated K1 values in the graphical method were not changed when scanning times were varied. We conclude that a two compartment model is acceptable for IMP kinetics within a scan time of 60 min. The graphical method gives a reliable and rapid estimation of rCBF when applied to dynamic data. PMID- 8441046 TI - Hepatobiliary scintigraphy: morphine-augmented versus delayed imaging in patients with suspected acute cholecystitis. PMID- 8441047 TI - Artificial intelligence: its use in medical diagnosis. AB - In nuclear medicine, analysis, interpretation and diagnosis may each be appropriate as applications for ANNs. Image processing and pattern recognition are two application areas of ANN technology that appear promising. An ANN (21) was used to classify normal and abnormal FDG-PET scans and performed better than discriminant analysis. Favorable results have been obtained from an ANN (22) in the interpretation of data recorded by experienced observers using various standard V/Q scans to determine the likelihood of pulmonary embolism. Carver Mead's book (23) on the development of hardware neural systems defines new approaches to ANN fabrication, including an electronic 100,000 transistor retina. As hardware is developed to permit the design of very large networks, we may expect many useful imaging applications to emerge for ANNs in the medical field. PMID- 8441048 TI - Graphic user interface-based nuclear medicine reporting system. AB - A graphically based, computerized report generation program has been developed and deployed at a dozen nuclear medicine facilities. The system is based on the Macintosh graphical user interface (GUI) and has been designed to be easy to learn and use. The system allows the nuclear medicine practitioner to generate reports for any nuclear medicine or nuclear cardiology procedure without transcriptionist support, dramatically decreasing report turnaround time. The system includes a relational database engine that allows cost-effective storage and rapid retrieval of final reports and also supports facsimile transmission of reports directly to referring clinicians' offices. PMID- 8441050 TI - NRC regulations on departures from manufacturer's instructions. PMID- 8441049 TI - Evaluating penile blood flow during tumescence. PMID- 8441051 TI - Correlation of radiation absorbed doses to nodal metastases. PMID- 8441052 TI - From monoclonal antibodies to peptides and molecular recognition units: an overview. AB - Various antigen-specific monoclonal antibodies (Mabs) are now being used clinically. Applications include in vitro testing (radioimmunoassay) and in vivo imaging (radioimmunoscintigraphy) for the early detection and staging of disease. Mabs can also be used as vehicles for delivering therapy (radioimmunotherapy) or to assess effects of therapeutic interventions. This review delineates those components making up antibody structure and discusses their functional significance. The method for radiolabeling immunoconjugates without altering their immunoreactivity or biological properties is dependent on an understanding of the structural units of the antibody and the labeling technique used. With the advent of genetic engineering, it has become feasible to design antibodies to circumvent certain adverse features or enhance a certain property. A review of the various "designer" antibodies and their relative advantages in the clinical setting is presented. PMID- 8441053 TI - Current imaging strategies for colorectal cancer. AB - Endoscopy and barium enema examinations are used to identify the primary site of disease in patients with clinical suspicion of colorectal cancer. Once colorectal cancer has been confirmed by imaging studies and biopsy, preoperative evaluation is directed toward accurate disease staging. Most currently available imaging techniques are inaccurate for detecting transmural extension, perienteric spread of tumors and distant lymph node involvement. Although both computed tomography (CT) and magnetic resonance imaging (MRI) have an unacceptably low sensitivity for accurate staging, CT is clearly superior to MRI for detecting extrahepatic metastases. Transrectal ultrasonography, however, is a promising new method for detecting perirectal spread of disease. The diagnostic efficacy of MRI and intravenous dynamic hepatic CT for detecting liver metastases is approximately equal. CT during arterial portography is recommended before resection of solitary liver metastases. Chest radiography is also part of the routine preoperative evaluation. Bone scans are rarely performed in patients without the skeletal pain suggestive of bone metastases. During the years following surgery for colorectal cancer, many patients undergo special imaging studies to identify local tumor recurrence, secondary tumor growth elsewhere within the large bowel and both regional and distant spread of disease. Thus, for the patient with a sharply increasing carcinoembryonic antigen level, CT of the abdomen and liver is the current recommendation. Immunoscintigraphy is a new imaging modality that addresses some of the limitations of current diagnostic procedures for colorectal cancer. This procedure gives whole body information on disease extent, especially in the extrahepatic abdomen and pelvis, and can therefore contribute to patient management decisions. PMID- 8441054 TI - Immunoscintigraphy in the surgical management of colorectal cancer. AB - The role of immunoscintigraphy in patients with colorectal cancer is being defined in ongoing clinical trials. Currently, most follow-up examination after "curative" resection of colorectal carcinoma are performed by surgeons, oncologists and gastroenterologists. They are largely focused on detecting recurrent intraluminal disease and measuring serial serum carcinoembryonic antigen (CEA) levels. Although rising CEA is often indicative of nonresectable disease, some patients with elevated CEA levels have no evidence of recurrent disease using conventional diagnostic modalities. In these patients, immunoscintigraphy will probably have a major diagnostic role. In addition, immunoscintigraphy may become valuable in screening patients at high risk for recurrence postoperatively, such as those with Dukes' stage C lesions, aneuploidy, poor tumor differentiation or tumor adhesion to or invasion of adjacent organs. Immunoscintigraphy may allow earlier diagnosis of recurrent disease and permit more targeted follow-up studies. Intensive, timely follow-up of these patients should lead to early detection of recurrent disease at a time when these lesions are still resectable. PMID- 8441055 TI - Clinical utility of immunoscintigraphy in managing ovarian cancer. AB - Ovarian cancer spreads to multiple areas of the peritoneal cavity early in the course of the disease. Multiple small foci of tumor are not identified readily with standard preoperative staging procedures. A review of an immunoscintigraphy study of more than 100 women preoperatively staged with 111In-labeled B72.3 (CYT 103) reveals that this technique has a low potential for serious side effects and it can identify miliary spread of ovarian cancer and extra-abdominal metastases. It has the potential to contribute favorably to patient management by detecting occult lesions, may define the extent of tumor as well or better than computerized tomography and may impact on surgical decision-making. PMID- 8441056 TI - Current applications of immunoscintigraphy in prostate cancer. AB - While adenocarcinoma of the prostate has always been one of the top three lethal malignant diseases in adult men, the ever-increasing size of the older male population due to prolonged life expectancy has added to the importance of this condition. It is estimated that over 133,000 new cases of prostatic cancer will be diagnosed this year and some 34,000 men will die from the disease. Thus, the importance of early detection and accurate staging has become more critical, particularly since safe and effective treatments are available. There is still considerable debate as to the most effective means of detection and routine screening procedures for prostatic cancer in men over the age of 50 yr. Digital rectal examination, prostatic-specific antigen determinations and rectal ultrasonography are the most successful and cost-effective screening procedures available. Regardless of the technique used, simple, accurate and reproducible staging is essential. Total surgical removal of the prostate, whether by radical retropubic or perineal approach, along with a lymph node dissection, is a potentially curative procedure. This is true provided the clinical staging is accurate and no undetected metastatic lesions are present. It is in this latter area that current technology is lacking. Routine technetium bone scans are not specific for prostatic cancer. Similarly, abdominal/pelvic computed tomography studies fail to detect lesions in localized prostatic cancer. A tumor-specific scan that detect not only bony lesions but also soft-tissue lesions would be optimal. Some believe that monoclonal antibodies directed at tumor-specific antigens afford this opportunity. We report on the Phase 1 clinical study results using an indium-labeled conjugate of the 7E11-C5.3 murine monoclonal antibody in patients with prostate cancer. PMID- 8441057 TI - Scintigraphic methods for detecting vascular thrombus. AB - Vascular thrombosis is a common and potentially life-threatening condition, but objective diagnosis is highly desirable before anticoagulant therapy is instituted. Existing nonscintigraphic modalities such as contrast venography and ultrasonography can image venous morphology but cannot reliably indicate the hematologic state of thrombi. Radiopharmaceuticals that bind specifically to fibrin or platelets afford the ability to determine whether a thrombus is hematologically active and therefore likely to propagate and/or embolize. Ideally, the test should produce a diagnostic result within a few hours and be capable of imaging thrombi that are several days old. A number of radiolabeled materials have been tested for their ability to bind to and permit scintigraphic detection of thrombi. These have included labeled fibrinogen, autologous platelets, monoclonal antibodies, fibrin fragment E1, plasminogen activators and synthetic peptides that mimic the molecular recognition units of antibodies. The current status of investigation of each of these radiopharmaceuticals is reviewed in this article. PMID- 8441058 TI - CT and SPECT image registration and fusion for spatial localization of metastatic processes using radiolabeled monoclonals. AB - The fusion of computed tomography (CT) and single-photon emission computerized tomography (SPECT) antibody images can enhance the information provided by either single modality by providing precise anatomical-functional correlation. Functional abnormalities seen on low resolution SPECT antibody images can be precisely located with specific anatomic structures seen in high resolution CT images. External fiducials located on each image modality aid in the automated registration, alignment and matching of CT and SPECT antibody images. The potential benefits of multimodal fusion include (A) the discrimination of more subtle activity peaks using anatomic organ segmentation, (B) temporal discrimination of recurrent disease, (C) assessment of residual activity post surgery and (D) automated localization of significant focal activity. In addition, the correlation of function with anatomy may be used to establish the physiologic status of ambiguously identified objects in the anatomic image. PMID- 8441059 TI - Insights from the hospital personnel survey. PMID- 8441060 TI - Evaluation of a clinical advancement system. AB - Evaluation of a nursing clinical advancement system was conducted to determine if it had achieved its goals: higher staff nurse job satisfaction and improved patient care. Findings included a trend toward higher job satisfaction and markedly lower turnover rates among clinically advanced staff. The subjective opinions of respondents supported a positive impact on patient care. The cost benefit ratio for this clinical advancement system, however, was negative. Recommendations for improving the credibility and effectiveness of such systems are presented. PMID- 8441061 TI - A multidisciplinary approach to case management of frail, hospitalized older adults. AB - Case management has been operationally defined in many ways, depending on the model and the needs of the population. This article describes a multidisciplinary resource utilization model of case management in a geriatric acute care medical unit that differs from many nursing- and protocol-driven case management models. The author discusses the design, implementation, and outcomes, which include improved quality of care, decreased length of stay, improved financial results, and increased physician compliance. PMID- 8441062 TI - Coalition building between public health nurses and parish nurses. AB - Community-based healthcare, particularly preventive healthcare services, requires mutual understanding and close cooperation between community healthcare providers. The authors describe the emergence of parish nursing, a new area of practice that emphasizes holistic healthcare, health promotion, and disease prevention activities. Similarities between public health and parish nursing practice, and the development of collaborative working relationships between these two groups of nurses are discussed. PMID- 8441063 TI - Research utilization in nursing administration. A graduate learning experience. AB - The authors describe a graduate learning experience designed to increase understanding and encourage the use of research utilization models to solve problems in nursing administration. One student project is described, and the extension of research utilization projects to include nursing administration research findings as well as clinical research findings is discussed. PMID- 8441064 TI - The advantages and risks of being a tax-exempt, nonprofit organization. AB - Most nonprofit hospitals enjoy exemptions from income, property, sales, and other taxes. The advantages of the tax exemption generally outweigh any disadvantages. Recent legislative and judicial challenges, however, have reduced the tax benefits of nonprofit hospitals. The authors review tax exemptions as they relate to hospitals, identify the primary advantages and risks, and highlight areas where nurse executives can further the exempt purpose of their institutions. PMID- 8441065 TI - Continuous quality improvement. Improving quality in your home care organization. AB - Total commitment to quality is an important factor in dealing with the competitive market and ensuring future survival. This article details the implementation of a continuous quality improvement program in one home care organization and examines initiation, implementation, and acceleration of the program over a period of just 16 months. It also illustrates how the same organization monitors clinical activities through quality assessment. PMID- 8441066 TI - Mentoring. The experience of nursing service executives. AB - Despite the popularity of mentoring, what is really known about its prevalence and application in the nursing service setting? This article presents views of 274 nursing service executives regarding their experience as proteges in the mentoring relationship. PMID- 8441067 TI - A collaborative practice model for the clinical nurse specialist. AB - This article describes a model of advanced nursing practice, jointly funded through nursing and medicine. The model is based on a matrix reporting structure with the clinical nurse specialist reporting to both a physician and a director of nursing. The authors discuss how the various role components are enacted and the benefits of the model to the specialist, institution, physicians, staff, and patients and their families. PMID- 8441068 TI - Panel urges nurses to take active role in information systems decisions. PMID- 8441069 TI - A collaboration model for solving the nursing shortage. PMID- 8441070 TI - How effective are your leadership skills? PMID- 8441071 TI - Study design in qualitative research: a guide to assessing quality. PMID- 8441072 TI - Return-visit intervals. PMID- 8441073 TI - Pneumonia decision making. PMID- 8441074 TI - Painful shoulder syndromes. PMID- 8441075 TI - Call nights and mortality. PMID- 8441076 TI - A clinical prediction rule for the diagnosis of ureteral calculi in emergency departments. AB - OBJECTIVE: To determine: 1) whether a simple clinical prediction rule could identify emergency department patients with ureteral calculi; 2) whether the kidney, ureter, and bladder (KUB) radiograph provides diagnostic information beyond that obtained from the history and physical examination; and 3) whether ureteral calculi can be diagnosed accurately in the emergency department without emergency excretory urography, commonly known as intravenous pyelography (IVP). PATIENTS: Two hundred three patients who underwent emergency KUB and IVP studies for nontraumatic abdominal or flank pain (derivation group) were retrospectively identified from radiology department records; 72 patients were prospectively evaluated in the emergency department for suspected ureteral stones (validation group). MEASUREMENTS: Clinical information included age, gender, characteristics of pain, associated symptoms, presence of fever, history of ureteral calculi, whether a stone was passed, and results of urinalysis and KUB and IVP studies. All KUB and IVP radiographs were independently reviewed by a radiologist blinded to the patient's clinical information and urinalysis results. DESIGN: Stepwise linear discriminant analysis was used to derive a four-item prediction rule from the derivation group and the validation group; the areas under the receiver operating characteristic (ROC) curves and the misclassification rates were compared. RESULTS: The four-item rule (acute onset, flank pain, hematuria, and positive KUB radiograph) correctly classified 83% of patients in the derivation group and 90% in the validation group. The four-item rule had an ROC area of 0.86 in the derivation group and 0.89 in the validation group. The KUB radiograph significantly improved the discriminant ability of the two history items and the urinalysis result. Thirty-three percent of patients were identified to be in a subset with a 96% probability of having a stone. CONCLUSION: These findings, which should be confirmed in another emergency department, suggest that subsets of patients with suspected ureteral calculi may be managed without emergency IVP; this approach thereby reduces the time a patient spends in the emergency department, radiation exposure, expense, and morbidity. PMID- 8441077 TI - Diagnosis of obstructive airways disease from the clinical examination. AB - OBJECTIVE: To determine the operating characteristics of history and physical examination items for pulmonary airflow obstruction. DESIGN: Prospective observational study. SETTING: Medical Preoperative Evaluation Clinic at the Durham Veterans Affairs Medical Center. PATIENTS/PARTICIPANTS: Consecutive patients referred for outpatient medical preoperative risk assessment. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Number of years the patient had smoked cigarettes, patient-reported wheezing [LR+ (likelihood ratio for finding present) = 3.1; LR- (likelihood ratio for finding absent) = 0.58], and auscultated wheezing (LR+ = 12; LR- = 0.87) were independent predictors of obstructive airways disease from the history and physical examination. Forced expiratory time and peak expiratory flow rate, both measured by the clinician at the bedside, were additional independent predictors of airflow obstruction. A nomogram using patient-reported wheezing, number of years the patient had smoked, and auscultated wheezing was developed and validated (area under receiver operating characteristic curve = 0.78; p = 0.0001) for the bedside prediction of obstructive airways disease. Peak expiratory flow rate can be substituted for auscultated wheezing with similar predictive ability. CONCLUSIONS: The results of bedside clinical examinations predict the presence of obstructive airways disease. A nomogram based on a combination of four bedside findings predicts airflow obstruction as well as clinicians' overall clinical impressions. PMID- 8441078 TI - Examiner dependence on physical diagnostic tests for the detection of splenomegaly: a prospective study with multiple observers. AB - OBJECTIVE: To determine the reliability and validity of various physical diagnostic techniques (including three methods of palpation and three methods of percussion) in detecting ultrasonographically identified splenomegaly. DESIGN: Prospective, double-blind study. SETTING: University hospital. PATIENTS: Twenty seven hospitalized male patients with suspected human immunodeficiency virus (HIV) infection. INTERVENTIONS: Three methods of palpation (bimanual, ballottement, and palpation from above) and three methods of percussion (as described by Nixon, Castell, and Barkun et al.) were performed on each patient by eight examiners. Splenic ultrasonography was performed within 96 hours of admission. MEASUREMENTS AND MAIN RESULTS: The prevalence of splenomegaly by ultrasonography (defined as a spleen > or = 13 cm on the longitudinal scan) in this population was 33.3%. The sensitivity and specificity of each method of palpation and percussion varied by examiner. The ranges of sensitivity across examiners for the three methods of palpation and the three methods of percussion were 0%-64.3% and 7.7%-75%, respectively. The ranges of specificity across examiners for the three methods of palpation and the three methods of percussion were 50%-100% and 60%-100%, respectively. Likelihood ratios pooled across observers revealed that for palpation, palpation from above, and percussion, Castell's method had the highest likelihood ratios [LR = 2.66 and 1.97, respectively; 95% CI = 1.52-4.64 and 1.22-3.19, respectively]. A combination of tests (either palpation or percussion) increased the diagnostic accuracy. CONCLUSION: Physical diagnostic techniques for the detection of splenomegaly are relatively insensitive but specific. In this study there was high interobserver variability, which did not appear to be associated to the level of experience. Combining tests increases diagnostic accuracy. PMID- 8441079 TI - Prevalence of depressive symptoms among established Vietnamese refugees in the United States: detection in a primary care setting. AB - OBJECTIVE: To determine the prevalence of depressive symptoms among Vietnamese refugees who have lived in the United States for at least two months. DESIGN: A prospective and descriptive study using the Vietnamese Depression Scale (VDS). Scores of > or = 13 on the VDS were considered indicative of depression. SETTING: Ten public health clinics in four states. PATIENTS/PARTICIPANTS: Four hundred seventy-six consecutive adult Vietnamese refugees presenting for primary care. INTERVENTIONS: The VDS, an 18-item culture-specific self-report measure, was used to screen for depressive symptoms. MEASUREMENTS AND MAIN RESULTS: Twenty percent of these patients had scores of 13 or above. Although being female; being older; being divorced, separated, or widowed; and being poorly educated were significant univariate risk factors for screening positive, only the latter two were significant in a multivariate model. Physical complaints were common and induced considerable anxiety about health status, but psychological and emotional symptoms were even more prevalent. Patients scoring 13 or higher had a higher rate of endorsement for every item in the scale than did those scoring lower than 13. CONCLUSIONS: This study substantiates the feasibility and importance of screening for depressive symptoms among Vietnamese refugees, particularly in primary care settings where they are most likely to seek care for both medical and psychological problems. PMID- 8441080 TI - The relevance to clinical practice of the certifying examination in internal medicine. AB - OBJECTIVE: To determine the relevance of the initial certifying examination to the practice of internal medicine and the suitability of items used in initial certification for recertification. DESIGN: Using a matrix-sampling approach, items from the 1991 Certifying Examination were assigned to two sets of judges: directors of the American Board of Internal Medicine (ABIM) and practicing general internists. Each judge rated the relevance of items on a five-point scale. PARTICIPANTS: 54 current or former directors of the ABIM and 72 practicing general internists; practitioners were nominated by directors and their ratings were included if they spent > 80% of their time in direct patient care. RESULTS: The directors' mean rating of all 576 items was 3.98 (SD = 0.62); the practitioners' mean rating was 4.11 (SD = 0.82). The directors assigned to 27 items ratings of less than 3 and the practitioners assigned to 42 items ratings of less than 3; seven of these items received low ratings from both groups. There were differences in the two groups' ratings of the relevance of various medical content categories, but the mean rating of core items was higher than that of noncore items and the mean rating of items testing clinical judgment was higher than that of items testing knowledge or synthesis. CONCLUSIONS: These findings suggest that the initial certifying examination is relevant to clinical practice and that many of the examination items are suitable for use in recertification. Differences in perception appear to exist between practitioners and directors, and the use of practitioner ratings is likely to be a routine part of judging the suitability of items for Board examinations in the future. PMID- 8441081 TI - NBME Examination Part I as a predictor of clinical and ABIM certifying examination performances. AB - The authors studied the extent that National Board of Medical Examiners examination Part I (NBME Part I) performance was predictive of American Board of Internal Medicine examination (ABIME) scores and clinical skill ratings. Information was obtained for Jackson Memorial Hospital internal medicine residents who completed training from 1980 to 1988. There was a highly significant association (r = 0.57, p < 0.0001, n = 117) between ABIME and NBME Part I scores. Clinical evaluations and NBME Part I scores were less strongly related. The data indicate that NBME Part I scores are highly predictive of ABIME outcome. NBME Part I scores also appear to be predictive of clinical performance, but to a lesser extent. PMID- 8441082 TI - Bacteremia in the elderly. AB - Bacteremia has a high mortality rate in all elderly populations, but especially nursing home residents and the hospitalized elderly. Elderly patients with bacteremia may present in a nonspecific fashion with incontinence, with falls, or afebrile. Mortality is greater in patients whose bacteremia originates outside the genitourinary tract or who are bacteremic with gram-positive organisms. Early appropriate treatment has been found to reduce mortality in some studies, especially in patients over 85 years old or with gram-positive bacteremias. Gram negative bacteremias are more common than those caused by gram-positive organisms in most studies. E. coli is the most common gram-negative isolate, followed in most studies by either Proteus or Klebsiella. Staphylococcus aureus is the most common gram-positive isolate; enterococcus and pneumococcus are also frequently isolated. Bacteremia in the elderly may present in a subtle fashion. Appropriate antibiotic therapy may reduce mortality and should include antibiotic coverage for S. aureus and gram-negative bacilli, as well as for anaerobes if pressure ulcers are suspected as the source. Clinicians who care for the elderly should be aware of the possible presentations of bacteremia and the appropriate treatment in all clinical settings. PMID- 8441084 TI - Bone marrow transplantation in children. PMID- 8441083 TI - Fibromyalgia: an age-old malady begging for respect. PMID- 8441085 TI - Framework for identifying children who have chronic conditions: the case for a new definition. AB - Efforts to identify children with ongoing health conditions generally rely on lists of diagnoses. However, there has been a growing trend to use a noncategorical, or generic, approach in which such children are identified by the consequences of their condition. Recent legislation and the Supreme Court decision in Sullivan v Zebley adopt this broader concept and mandate that a noncategorical approach be used in determining eligibility for services and benefits. Traditional condition lists are less desirable because (1) every disorder to which children are subject cannot be included, (2) diagnoses may be applied inconsistently by clinicians and across settings, (3) condition labels alone do not convey the extent of morbidity for individuals, (4) there is a bias toward identifying only those children who have access to the medical care system, and (5) there is often a gap between emergence of symptoms or consequences and diagnosis. We developed a noncategorical framework for identifying children with ongoing health conditions that responds to the federal mandate and uses consequences of disorders, rather than diagnostic labels. It can be applied to meet the objectives of services, research, policy, reimbursement, or program eligibility; is consistent across diagnoses; is descriptive of the impact of morbidity; is adaptable to meet specific purposes; and can be modified by imposing different severity levels. Our screening tool will soon be available for practical use. PMID- 8441086 TI - Bone mineralization in the first year of life in infants fed human milk, cow-milk formula, or soy-based formula. AB - OBJECTIVE: To test the hypotheses that (1) bone mineral content (BMC) is similar in infants fed soy-based formula (SBF) and human milk (HM) and higher in infants fed cow milk-based formula (CBF) and (2) serum 1,25-dihydroxyvitamin D, an index of mineral sufficiency, is similar in infants fed formula and infants fed HM. DESIGN: Randomized, prospective study of formula-fed group only. SETTING: Recruitment was in a normal newborn nursery. PATIENTS: 72 infants: 10 given HM, 20 given CBF (Similac), 21 given SBF (Isomil), and 21 given SBF (Prosobee). MEASUREMENTS: BMC and 1,25-dihydroxyvitamin D levels at baseline (days 2 through 7 of life) and at 8, 16, 26, and 52 weeks of age. The BMC was similar in all groups at all times; serum 1,25-dihydroxyvitamin D levels were similar in all groups, except that they were elevated at 8, 16, and 26 weeks in those fed Prosobee. CONCLUSIONS: (1) BMC is similar in SBF-, CBF-, and HM-fed infants and (2) compensatory elevation of serum 1,25-dihydroxyvitamin D concentrations may occur in SBF-fed infants. PMID- 8441087 TI - Lumbar puncture in children with periorbital and orbital cellulitis. AB - OBJECTIVE: To measure the frequency with which lumbar puncture (LP) was performed in children with periorbital and orbital cellulitis in the years 1979 through 1991, and to examine its value as a diagnostic test in these patients. DESIGN: Retrospective review of both computerized discharge diagnoses and medical records. SETTING: Tertiary care hospital. PATIENTS: Two hundred fourteen children younger than 18 years of age discharged between Jan. 1, 1979, and Dec. 31, 1991, with a final diagnosis of periorbital or orbital cellulitis. MAIN OUTCOME MEASURES: Rates of LP and of bacterial meningitis. RESULTS: Of the 214 patients, 96 (45%) had LPs. Two children (1%) had meningitis; in both, the diagnosis was strongly suspected before the LP was performed. No other subject had a discharge diagnosis of meningitis. During the 13 years of study, the proportion of patients in whom LP was performed increased from 14% in the first 6 years (1979 through 1984) to 62% from 1985 through 1991 (p < 0.0001). Those older than 2 months who were afebrile on arrival in the emergency department were 12.4 times more likely to have an LP in 1985 through 1991 than in 1979 through 1984 (p = 0.005). CONCLUSIONS: The increase in the number of LPs performed from 1985 through 1991 in children with periorbital or orbital cellulitis was not accompanied by an increase in the diagnosis of early or unsuspected meningitis. These data suggest the need for more judicious use of LP in children with periorbital swelling. PMID- 8441088 TI - Hospitalization of very low birth weight children at school age. AB - OBJECTIVE: To assess whether very low birth weight (VLBW) increases the risk of hospitalization at school age. DESIGN: Prospective, multisite cohort study. PARTICIPANTS: Selected from a previous multisite, hospital-based trial, 611 VLBW children, and, from a prior representative sample, 724 children who weighed 1501 to 2500 gm and 533 who weighed > 2500 gm. All the children were re-contacted at 8 to 10 years of age for this study. METHODS: Maternal interview with the use of standardized questions. MAIN OUTCOME: Hospitalization in year before interview. RESULTS: The VLBW children were three or four times more likely to be rehospitalized than children of normal birth weight, both in the year before the interview (7% vs 2%) and since birth (50% to 60% vs 22%). Morbidity and Medicaid coverage increased the risk of hospitalization in the year before the interview; non-white race decreased it. After control for other factors, however, lower birth weight remained a significant risk factor for hospitalization. CONCLUSIONS: The VLBW children continue to have an increased risk of hospitalization; the risk is similar in magnitude to that seen in infancy. PMID- 8441089 TI - Pulmonary function abnormalities in childhood sickle cell disease. AB - Pulmonary function tests in adults with sickle cell disease have shown a restrictive pattern that has been attributed to the sequelae of acute chest syndrome (ACS). We compared pulmonary function test results in 37 children with sickle cell anemia (20 with SS hemoglobin (HbSS), 14 with SC hemoglobin, and 3 with S beta hemoglobin) with those in 22 control subjects matched for sex, race, and height and compared pulmonary function in patients with and without a history of ACS. Of the 10 patients with a history of ACS, all but one had HbSS. Pulmonary function tests measured forced vital capacity (FVC), the diffusion capacity of carbon monoxide, and the plethysmographic determination of lung volumes. The FVC and forced expiratory volume in 1 second (FEV1), expressed as the percentage of the predicted value, were significantly less for those with HbSS with or without a history of ACS than for control subjects (p < 0.05), but the FEV1/FVC ratio, an index of airway obstruction, was normal in all groups. Total lung capacity was also significantly lower in patients with HbSS with or without a history of ACS than in control subjects (p < 0.05), but the ratio of residual volume to total lung capacity, another index of airway obstruction, was normal. We conclude that children with sickle cell disease, particularly those with HbSS, may have abnormally small lungs that function normally relative to their size; clustering of ACS episodes is not specifically associated with the observed abnormality. PMID- 8441090 TI - Panniculitis and fever in children. AB - We describe three children with panniculitis and associated systemic manifestations including fever. Histopathologic features, such as the presence of lobular or septal inflammation, presence of vasculitis, character of the cellular infiltrate, and presence of erythrophagocytosis, were useful in classifying this group of panniculitides. In one patient with subcutaneous polyarteritis nodosa, corticosteroid therapy was effective; in two other patients with histiocytic cytophagic panniculitis, there were poor responses to steroids, intravenously administered immune globulin, dapsone, or antimalarial drugs; cyclosporine was very effective and appeared to be the drug of choice. PMID- 8441091 TI - Association of facial hemangiomas with Dandy-Walker and other posterior fossa malformations. AB - Cutaneous hemangiomas are common benign tumors of infancy that only rarely are associated with malformations in other tissues or organs. We report nine infants with large facial hemangiomas who also had Dandy-Walker malformations or similar posterior fossa abnormalities. On the basis of the experience with our patients and with those previously reported, we recommend radiographic imaging studies of the brain of infants with large, aggressive facial hemangiomas to rule out posterior fossa defects. PMID- 8441092 TI - Cholelithiasis in infancy: a study of 40 cases. AB - During a 17-year period, 40 infants less than 1 year of age were investigated for cholelithiasis; 32 infants were seen within the past 10 years. Seventeen of them had no recognizable predisposing factors. In 6 infants, gallbladder lithiasis was a fortuitous finding on a plain radiograph or sonogram with no signs of common bile duct obstruction; under conservative management, no complications of lithiasis were observed on follow-up of 3 infants and spontaneous resolution occurred in 2 others. In the remaining 34 infants with lithiasis of the common duct or cystic duct or both, the initial symptoms were cholestatic jaundice in 21, acholic stools in 8, sepsis in 4, and abdominal pain in 1. Ultrasonography, performed in 33 of them, showed dilation of the biliary tract in 28, and stones in the gallbladder in 13 and in the bile ducts in 10. Percutaneous transhepatic cholangiography or operative cholangiography in 26 infants showed stones in the bile ducts in 23. In 3 infants, no lithiasis was visible, suggesting the spontaneous elimination of stones. Treatment was initially surgical in 9 infants, but starting in 1981 interventional radiologic procedures were attempted in 15 infants and were successful in 12. Spontaneous resolution of cholelithiasis occurred in 10 other infants with cholestasis. Recurrence of biliary stones was observed in 3 infants only after a follow-up of 7 months to 10 years. These results suggest that common bile duct lithiasis should be considered among the causes of cholestatic jaundice in infancy, and that some of the gallbladder calculi found in older children may have resulted from a lithogenic process that occurred during fetal life or shortly after birth. Percutaneous cholangiography with biliary drainage appears to be an effective means of treatment of infants with common bile duct obstruction; surgery can then be restricted to a limited number of cases, especially those with associated strictures of the bile ducts. PMID- 8441094 TI - Factors predictive of sustained growth in children after renal transplantation. The North American Pediatric Renal Transplant Cooperative Study. AB - To ascertain growth and rehabilitation of children after transplantation, the North American Pediatric Renal Transplant Cooperative Study collected growth data on renal transplant recipients. From January 1987 through December 1990, a total of 1553 children with one or more transplants were entered into the study by its 75 participating centers. Of these, the first 300 children with a functioning graft and 2 years of linear growth data form the cohort for this study. For the total cohort of 300 patients, the mean (+/- SEM) baseline height z score was 2.41 +/- 0.09, and the change in z score determined after 2 years was 0.18 +/- 0.06 (p < 0.01). Children in the age group from birth to 1 year had the maximal deficit and had the maximal improvement in z score, gaining about 1 SD (p < 0.01). For the 2- to 5-year-old group, the change in z score was about 0.5 SD (p < 0.001). No improvement in z score was noted for children 6 to 17 years of age. Each increase in serum creatinine concentration of 90 mumol/L (1 mg/dl) was associated with -0.17 decrease in the z score (p < 0.001). Gender, donor source, history of previous transplantation, and prior dialysis were not associated with a significant change in the z score; thus the increased rate of growth during the first 2 post-transplantation years occurred mainly in subjects less than 6 years of age. PMID- 8441093 TI - Nephrolithiasis, hypocitraturia, and a distal renal tubular acidification defect in type 1 glycogen storage disease. AB - Renal stones containing calcium can occur in patients with type 1 glycogen storage disease. We studied 11 patients with glycogen storage disease. Five patients had renal calculi, nephrocalcinosis, or both, and five had hypercalciuria. Serum levels of calcium, phosphorus, parathyroid hormone, and urate were normal. Serum levels of 1,25-dihydroxyvitamin D were elevated in each patient. None of the patients had a metabolic acidosis, but all nine who were tested had evidence of impaired acid excretion. In response to an acid load, eight of the nine patients had subnormal titratable acid excretion, and nine had subnormal ammonia excretion; six of nine patients were unable to secrete hydrogen ions in response to bicarbonate administration. These data indicate that patients with type 1 glycogen storage disease have an incomplete form of distal renal tubular acidosis. This may be the cause of hypercalciuria and nephrocalcinosis in these patients. PMID- 8441095 TI - A decline in Haemophilus influenzae type b meningitis. PMID- 8441096 TI - Responses of children to booster immunization with their primary conjugate Haemophilus influenzae type B vaccine or with polyribosylribitol phosphate conjugated with diphtheria toxoid. AB - Children primed with one of four conjugate Haemophilus influenzae type b vaccines received booster immunization with their primary vaccine or with polyribosylribitol phosphate conjugated with diphtheria toxoid. The latter vaccine produced postbooster antibody levels that equaled or exceeded those produced by boosting with the original vaccine, and thus may be used as a booster irrespective of the original vaccine. PMID- 8441097 TI - Confirmation of transpyloric feeding tube placement by ultrasonography. AB - We compared ultrasonography with radiography for placement of transpyloric feeding tubes. Ultrasound study successfully determined tube tip position and gave functional information unavailable with radiography, allowing for greater accuracy of placement and the observation of transpyloric reflux of feedings. PMID- 8441099 TI - Ornithine transcarbamylase deficiency presenting with strokelike episodes. AB - A girl with ornithine transcarbamylase deficiency had a history of recurrent strokelike episodes. The differential diagnosis of unexplained stroke should include primary urea cycle defects. PMID- 8441098 TI - Elevated serum aminotransferase activity as an early manifestation of gluten sensitive enteropathy. AB - Six children in whom long-standing hypertransaminasemia of unknown cause led to an initial diagnosis of chronic or protracted cryptogenic hepatitis were found to have asymptomatic celiac disease. Administration of a gluten-free diet caused a prompt improvement of both hepatic and intestinal biochemical/histologic abnormalities. Hepatic damage may be another "atypical" form of celiac disease in children. PMID- 8441100 TI - Treatment of somnambulism with anticipatory awakening. AB - A 8-year-old boy with a 6-year history of parasomnia (twice-weekly sleepwalking with enuresis) was treated by awakening him for 5 nights before the episodes. The sleepwalking stopped entirely. Anticipatory awakening may be a simple, inexpensive, low-risk therapy for somnambulism. PMID- 8441101 TI - Methylmalonic acidemia with a severe chemical but benign clinical phenotype. AB - A 5-year-old boy of West African origin had methylmalonic acidemia with a mut- enzyme phenotype, no clinical response to hydroxycobalamin, and metabolite measurements indicative of the severe form of mutase deficiency. His development, both mental and physical, was satisfactory and he had no episodes of metabolic decompensation. The explanation for the neurotoxic effects and metabolic decompensation in typical methylmalonic acidemia and the (allelic) genotype that explains this patient's phenotype are uncertain. PMID- 8441102 TI - Spinal cord injury at birth: diagnostic and prognostic data in twenty-two patients. AB - OBJECTIVES: To establish criteria, evident soon after birth, that predict long term outcome of neonates with spinal cord injury (SCI) at birth. DESIGN: Retrospective case-series. SETTING: Five Canadian regional neonatal tertiary care centers. PATIENTS: Consecutive samples of patients referred to five centers for a total of 22 subjects, in whom SCI was diagnosed during life. Sites of lesions were above the fourth cervical vertebrae (n = 14), at the fourth cervical to the fourth thoracic vertebrae (n = 6), and at the thoracolumbar region (n = 2). MEASUREMENTS AND MAIN RESULTS: All 14 patients with upper cervical SCI had cephalic presentations, whereas all 6 patients with cervicothoracic SCI had breech presentations (p < 0.0001). The site and extent of lesion were best diagnosed by clinico-imaging correlations. Ultrasonography appeared to be the most useful imaging study. In patients with upper cervical SCI who had no coexistent central nervous system abnormality associated with early death, long term outcome in survivors (dependency on mechanical ventilation and on aids for upper limb activity and for ambulation) was best predicted by age when breathing was first observed and by rate of recovery of limb motor function in the first 3 months. The presence of breathing movements on day 1 (n = 2) was associated with mild disability. The absence of breathing movements on day 1 and little or no recovery of motor function in the first 3 months was associated with permanent total dependency on mechanical ventilation and severe quadriplegia (n = 5). Apnea on day 1 and intermediate recovery rates in the first 3 months was associated with variable long-term prognoses (n = 3). PMID- 8441103 TI - Risk of intracranial hemorrhage and other adverse outcomes after cocaine exposure in a cohort of 323 very low birth weight infants. AB - We conducted a prospective cohort study of 323 consecutively born very low birth weight infants (< or = 1499 gm) to determine any association between prenatal cocaine exposure and (1) intracranial ultrasonographic abnormalities and (2) other adverse perinatal outcomes. The infants were assigned to either a cocaine exposed group (n = 86) or a cocaine-nonexposed group (n = 146) on the basis of combined detection methods for prenatal maternal cocaine abuse including maternal history, maternal and infant urine immunoassay (Emit), and meconium analysis (high-performance liquid chromatography and gas chromatography-mass spectrometry). Ninety-one infants were not assigned because of early death before complete testing (n = 80) or missed tests (n = 11). The detected incidence of cocaine exposure in the assigned population was 37% (86/232). Meconium testing with high-performance liquid chromatography and gas chromatography-mass spectrometry was the sole means of detection in 30% (26/86) of cases. The cocaine nonexposed infants did not differ from the cocaine-exposed infants in the incidence of intraventricular hemorrhage (36% vs 35%), grades III and IV intraventricular hemorrhage (14% vs 14%), or periventricular leukomalacia (4% vs 2%). Adverse outcomes increased by cocaine exposure were abruptio placentae (8% vs 18%; p = 0.046), surgical ligation of a patent ductus arteriosus (1% vs 7%; p = 0.02), and seizures (5% vs 17%; p = 0.004). We conclude that prenatal cocaine exposure does not increase the incidence or severity of intracranial hemorrhage or periventricular leukomalacia but does increase the risk of abruptio placentae, surgical ligation of a patent ductus arteriosus and seizures in very low birth weight infants. PMID- 8441104 TI - Long-term pulmonary consequences of respiratory distress syndrome in preterm infants treated with exogenous surfactant. AB - The pulmonary outcome for preterm infants 1 year after synthetic surfactant replacement for respiratory distress syndrome was assessed by examining their pulmonary status and the results of pulmonary function tests. A total of 47 infants were followed: 13 infants mean +/- SD: birth weight, 1960 +/- 616 gm; gestation, 32 +/- 1.1 weeks) had been assigned to the placebo group and 34 (birth weight = 1890 +/- 530 gm; gestation = 32 +/- 2.5 weeks) to surfactant treatment. The infants were examined at 3 to 6 months of age (n = 45) and at 9 to 12 months of age (n = 36). There were no significant differences between the two groups in predisposing clinical conditions that would lead to chronic lung disease. The infants had similar patterns of growth, respiratory-related illness, and need for theophylline therapy, diuretic therapy, or both. None had hypoxemia by pulse oximetry. Mean (+/- SEM) values for pulmonary mechanics and energetics in surfactant-treated infants were significantly (p < 0.01) lower for total pulmonary resistance in late infancy (57.7 +/- 11.7 vs 35.3 +/- 4.6 cm H2O/L per second). Lower values (mean +/- SEM) of resistive work of breathing were also measured in the surfactant-treated group (60.7 +/- 12.0 vs 38.2 +/- 3.6 gm-cm/kg per breath). The dynamic pulmonary compliance values were in the low-normal range for both groups, and the mean (+/- SEM) peak-to-peak esophageal pressure values were elevated (11.47 +/- 2.26 cm H2O in the placebo group; 9.24 +/- 0.69 cm H2O in the surfactant group). Forced expiratory flow measurements in late infancy demonstrated significant (p < 0.01) improvement in expiratory reserves and reduced evidence of airflow obstruction in the surfactant-treated infants (peak flow (mean +/- SEM): 287.1 +/- 69 vs 396.9 +/- 27 ml/sec; forced expiratory flow (mean +/- SEM) at functional residual capacity: 56.3 +/- 7.5 vs 83.4 +/- 19.5 ml/sec). No significant differences in pulmonary functions were noted in early infancy. These data suggest that surfactant replacement for respiratory distress syndrome may be associated with beneficial long-term effects on the resistive airflow properties of larger preterm infants. PMID- 8441105 TI - Comparison of three dosing procedures for administration of bovine surfactant to neonates with respiratory distress syndrome. AB - A multicenter, randomized, double-blind, controlled trial compared three beractant (Survanta) administration procedures in the treatment of neonatal respiratory distress syndrome. Infants weighing > or = 600 gm with respiratory distress syndrome who required assisted ventilation were treated within 8 hours of birth with beractant administered intratracheally. Procedure A required administration in two fractional doses after removal of the infant from the ventilator. Procedure B required administration in two fractional doses through a neonatal suction valve and did not require removal of the infant from the ventilator, and procedure C required administration in four fractional doses during removal from the ventilator. Procedure C is the method used in all previous beractant studies. Of the 299 infants enrolled, 103 were randomly assigned to procedure A, 100 to procedure B, and 96 to procedure C. The results indicate no significant differences among the treatment groups in the clinical outcome measures of fractional inspired oxygen, mean airway pressure, and arterial-alveolar ratio of partial pressure of oxygen at 72 hours of life, or in the incidences of air leaks, pulmonary interstitial emphysema, or death through 72 hours of life. There were no significant differences in the lowest heart rates recorded during administration of doses, but there was less oxygen desaturation during administration of dose 1 with procedure B than with procedure A (p = 0.001), and more reflux of beractant after procedure B than after procedure C (p = 0.007). We conclude that the three procedures are equally effective and can be used to administer beractant safely and effectively. Procedure B has the advantage of allowing administration without interrupting mechanical ventilation. PMID- 8441106 TI - Elevated 1,25-dihydroxyvitamin D serum concentrations in infants with subcutaneous fat necrosis. AB - Two infants with subcutaneous fat necrosis had hypercalcemia that normalized during glucocorticoid treatment. The combination of hypercalcemia, normal concentration of 25-hydroxyvitamin D, an elevated concentration of 1,25 dihydroxyvitamin D, a suppressed parathyroid hormone level, and low-normal bone turnover indicated abnormal 1,25-dihydroxyvitamin D production with increased intestinal absorption of calcium. Unregulated production of 1,25-dihydroxyvitamin D by the granulomatous cells of fat necrosis may cause hypercalcemia. PMID- 8441107 TI - Hospital treatment of asthma: lack of benefit from theophylline given in addition to nebulized albuterol and intravenously administered corticosteroid. AB - STUDY OBJECTIVE: To determine the efficacy of theophylline when given in addition to nebulized albuterol and intravenously administered corticosteroid to children hospitalized with mild to moderate asthma. DESIGN: Randomized, prospective, placebo-controlled, double-blind trial. SETTING: Tertiary-care children's hospital. PATIENTS: Twenty-nine patients with asthma between the ages of 2 and 16 years completed the study. The treatment and placebo groups were similar in age, gender, race, illness severity, and emergency department treatment. INTERVENTIONS: All patients received intravenously administered methylprednisolone and nebulized albuterol. The treatment group received intravenous theophylline therapy and the placebo group dextrose in water. When intravenously administered medications were discontinued, therapy continued with oral administration of theophylline (or placebo) and of prednisone. MEASUREMENTS AND MAIN RESULTS: Twice-daily assessments of clinical asthma symptoms were made by using a scoring system consisting of respiratory rate, inspiratory/expiratory ratio, wheeze, and accessory muscle use. Time required to reach study discharge criteria (asthma score < or = 2) (30.4 +/- 16.8 vs 27.0 +/- 10.3 hours; p = 0.51) and the rate of improvement of the clinical asthma score (-0.10 +/- 0.05 unit/hr vs -0.11 +/- 0.09 unit/hr; p = 0.88) were not significantly different between the theophylline and placebo groups. The number of albuterol aerosol treatments required and the adverse effects experienced were not significantly different between groups. CONCLUSION: When the combination of systemically administered corticosteroid and inhaled albuterol is used in the treatment of children hospitalized with mild to moderate asthma, addition of theophylline may not be justified. PMID- 8441108 TI - Efficacy of intravenously administered theophylline in children hospitalized with severe asthma. AB - PURPOSE: To determine whether intravenously administered theophylline, when added to frequently nebulized albuterol and intravenously administered methylprednisolone, benefits children hospitalized with severe asthma. DESIGN: Prospective, randomized, placebo-controlled, parallel-group, double-blind study. SETTING: Inpatient pediatric service at a tertiary-care teaching hospital. PATIENTS: Twenty-one children 5 to 18 years of age. INTERVENTIONS: All patients received 2.5 to 5.0 mg of nebulized albuterol every 20 minutes to every 6 hours, intravenously administered methylprednisolone (1 mg/kg every 6 hours), and either intravenously administered theophylline (as aminophylline) or placebo for 36 hours. Serum theophylline concentrations were maintained between 55 and 110 mumol/L (between 10 and 20 micrograms/ml) by adjusting loading doses and continuous infusion rates. MEASUREMENTS AND MAIN RESULTS: Forced expired volume in 1 second (FEV1) and clinical score were measured at 0, 1, 3, 6, 12, 24, and 36 hours after the start of each individual study. The total number of nebulizations, total albuterol dosage, adverse effects, and duration of hospital stay were recorded. Twelve children received theophylline and nine received placebo. The two groups did not differ significantly in age, sex, or baseline FEV1. In both groups, clinical score significantly improved from baseline by 12 hours, and FEV1 by 24 hours (p < 0.05). There were no significant differences between the groups in FEV1 or clinical score at any of the measured time points. There were no significant differences in rate of improvement in FEV1, total number of nebulizations, total albuterol dosage, or duration of hospital stay. Adverse effects were mild and infrequent and did not differ significantly between the two groups. CONCLUSIONS: Theophylline, at therapeutic concentrations, did not additionally benefit children hospitalized with severe asthma who were being treated frequently with nebulized albuterol and with methylprednisolone intravenously. PMID- 8441109 TI - Use of cholestyramine in the treatment of children with familial combined hyperlipidemia. AB - We studied the effectiveness of and compliance with the use of cholestyramine in children with heterozygous familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCHL). During a 10-year period, 673 children (aged 10.5 +/- 4.0 years) were referred for evaluation of hyperlipidemia, of whom 87 (36 with FH; 51 with FCHL) were treated with cholestyramine (8 to 24 gm/day). In both groups, total cholesterol, low-density lipoprotein (LDL)-cholesterol, and apolipoprotein B levels were significantly reduced after cholestyramine use. In those with FH, plasma LDL-cholesterol levels decreased from 258 +/- 35 mg/dl (6.67 +/- 0.90 mmol/L) to 190 +/- 31 mg/dl (4.91 +/- 0.80 mmol/L); in those with FCHL, LDL-cholesterol levels dropped from 207 +/- 40 mg/dl (5.35 +/- 1.03 mmol/L) to 141 +/- 35 mg/dl (3.64 +/- 0.90 mmol/L). High-density lipoprotein-cholesterol levels were not significantly changed after cholestyramine use in either group. In the FCHL group, plasma triglyceride levels increased significantly from 81 +/- 35 mg/dl (0.92 +/- 0.40 mmol/L) to 134 +/- 42 mg/dl (1.52 +/- 0.48 mmol/L). Seven patients were lost to follow-up; 18 discontinued the medication within 1 month. Of the remaining 62 children, 59 had a good response to the drug. Of the 62 patients, 52 discontinued the medication after 21.9 +/- 10 months. Adverse effects included foul taste (73%), nausea with bloating (18%), and constipation. Cholestyramine is effective in reducing LDL-cholesterol levels in children with inherited hyperlipidemia, but the majority of children will not comply with its long-term use. PMID- 8441110 TI - Use of play with clay to treat children with intractable encopresis. AB - We used play with modeling clay to treat six children, aged 4 to 12 years, with a history of intractable constipation with encopresis for a mean of 5.4 (2 to 8) years, refractory to treatment; biofeedback therapy had not been tried. Clay was chosen because, as a brown, messy material, it was a metaphor for feces and could let the child express either his disgust or aggressivity, or let him build symbolic structures. No interpretation was made during treatment. Four children had no symptoms during 2 months of therapy and no relapse during 1 year of follow up, one child improved significantly, and one child failed to respond but withdrew from treatment after only three sessions. Modeling clay may be a cheap and effective treatment modality for refractory constipation with encopresis. PMID- 8441111 TI - Behavior profile of children with severe breath-holding spells. AB - Thirty-two children with severe breath-holding spells and 42 control children were studied by using the Child Behavior Checklist. No single behavioral profile could identify children with breath-holding spells, and there were no group differences with respect to individual behavior categories, broad-band profiles, or total scores. No correlation was found between frequency of breath-holding spells and profile scores. PMID- 8441112 TI - Grover Powers. PMID- 8441113 TI - Fruit juice and chronic nonspecific diarrhea. PMID- 8441114 TI - Congenital heart disease in trisomy 21 mosaicism. PMID- 8441115 TI - Multicystic-dysplastic kidney and contralateral urologic abnormalities. PMID- 8441116 TI - Effect of respiratory syncytial virus infection on theophylline disposition. PMID- 8441117 TI - Breath hydrogen excretion in infancy. PMID- 8441118 TI - Carnitine status during prolonged total parenteral nutrition. PMID- 8441119 TI - Pseudo-glutaric aciduria type II in a patient with celiac disease. PMID- 8441120 TI - Stereoselective detection of amino acids by lobster olfactory receptor neurons. AB - 1. Biochemical and electrophysiological assays were used to test the hypothesis that the olfactory system of the Caribbean spiny lobster, Panulirus argus, contains populations of chemosensory receptors that are differentially sensitive to the L- and D-stereoisomers of the amino acid alanine. 2. Independent binding sites for L-alanine (dissociation constant (KD) of 6.6 microM and maximum binding (Bmax) of 16.8 fmole/microgram protein) and for D-alanine (KD of 21.6 microM and Bmax of 17.8 fmole/microgram protein) were characterized biochemically. The interaction of ligand with each binding site is rapid, reversible and saturable with respect to both time and concentration. 3. Based on a difference of at least 20% in the relative sensitivity of an olfactory receptor cell to alanine enantiomers, 44% and 34% of the 77 neurons tested were classified as L-alanine and D-alanine sensitive, respectively. The relative sensitivity to alanine enantiomers was independent of the concentration tested. Stereoselective receptors are likely for 17 of 20 other amino acids tested. 4. The congruence of biochemical and electrophysiological results leads to the conclusion that the lobster's responses to D- and L-alanine are mediated by receptors specific for each stereoisomer and that the receptors are differentially distributed among receptor cells. PMID- 8441121 TI - Labile cochlear tuning in the mustached bat. I. Concomitant shifts in biosonar emission frequency. AB - The cochlea of the mustached bat (Pteronotus parnellii) has sharp tuning characteristics and pronounced resonance within a narrow band near the second harmonic, constant frequency (CF2) component of the animal's biosonar signals. That fine frequency discrimination occurs within this narrow band is evident from Doppler-shift compensation, whereby bats in flight lower the frequency of emitted CF2s to maintain returning echoes within this band. This study examined various factors capable of producing shifts in both the cochlear resonance frequency (CRF) and CF2s emitted by stationary bats and bats actively Doppler-shift compensating on a pendulum. Each of three experimental factors shifted the CRF in a reversible manner. Changes in body temperature produced an average CRF shift of 39 +/- 18 Hz/degrees C. The CRF increased with flight by 150 +/- 100 Hz and returned to baseline values within 10 min after flight. Contralateral sound exposure produced smaller (100 +/- 20 Hz), rapid shifts in the CRF, suggesting that a mechanism different from the temperature- and flight-related shifts was involved. Changes in the CRF induced by temperature and flight were accompanied by shifts in the emitted CF2 of stationary and moving bats. Coupled with a companion study of associated shifts in neural tuning, the concomitant changes in CRF and CF2 provide evidence of cochlear tuning lability in the mustached bat. PMID- 8441122 TI - Labile cochlear tuning in the mustached bat. II. Concomitant shifts in neural tuning. AB - Acoustic stimuli near 60 kHz elicit pronounced resonance in the cochlea of the mustached bat (Pteronotus parnellii parnellii). The cochlear resonance frequency (CRF) is near the second harmonic, constant frequency (CF2) component of the bat's biosonar signals. Within narrow bands where CF2 and third harmonic (CF3) echoes are maintained, the cochlea has sharp tuning characteristics that are conserved throughout the central auditory system. The purpose of this study was to examine the effects of temperature-related shifts in the CRF on the tuning properties of neurons in the cochlear nucleus and inferior colliculus. Eighty-two single and multi-unit recordings were characterized in 6 awake bats with chronically implanted cochlear microphonic electrodes. As the CRF changed with body temperature, the tuning curves of neurons sharply tuned to frequencies near the CF2 and CF3 shifted with the CRF in every case, yielding a change in the unit's best frequency. The results show that cochlear tuning is labile in the mustached bat, and that this lability produces tonotopic shifts in the frequency response of central auditory neurons. Furthermore, results provide evidence of shifts in the frequency-to-place code within the sharply tuned CF2 and CF3 regions of the cochlea. In conjunction with the finding that biosonar emission frequency and the CRF shift concomitantly with temperature and flight, it is concluded that the adjustment of biosonar signals accommodates the shifts in cochlear and neural tuning that occur with active echolocation. PMID- 8441123 TI - Passive sound localization of prey by the pallid bat (Antrozous p. pallidus). AB - The pallid bat (Antrozous p. pallidus) uses passive sound localization to capture terrestrial prey. This study of captive pallid bats examined the roles of echolocation and passive sound localization in prey capture, and focused on their spectral requirements for accurate passive sound localization. Crickets were used as prey throughout these studies. All tests were conducted in dim, red light in an effort to preclude the use of vision. Hunting performance did not differ significantly in red light and total darkness, nor did it differ when visual contrast between the terrestrial prey and the substrate was varied, demonstrating that the bats did not use vision to locate prey. Our bats apparently used echolocation for general orientation, but not to locate prey. They did not increase their pulse emission rate prior to prey capture, suggesting that they were not actively scanning prey. Instead, they required prey-generated sounds for localization. The bats attended to the sound of walking crickets for localization, and also attacked small, inanimate objects dragged across the floor. Stationary and/or anesthetized crickets were ignored, as were crickets walking on substrates that greatly attenuated walking sounds. Cricket communication sounds were not used in prey localization; the bats never captured stationary, calling crickets. The accuracy of their passive sound localization was tested with an open-loop passive sound localization task that required them to land upon an anesthetized cricket tossed on the floor. The impact of a cricket produced a single 10-20 ms duration sound, yet with this information, the bats were able to land within 7.6 cm of the cricket from a maximum distance of 4.9 m. This performance suggests a sound localization accuracy of approximately +/- 1 degree in the horizontal and vertical dimensions of auditory space. The lower frequency limit for accurate sound localization was between 3-8 kHz. A physiological survey of frequency representation in the pallid bat inferior colliculus suggests that this lower frequency limit is around 5 kHz. PMID- 8441124 TI - International Society for the Study of Vulvar Disease. PMID- 8441125 TI - Vulvitis circumscripta plasmacellularis. A clinicopathologic entity? AB - Four cases of vulvitis circumscripta plasmacellularis (plasma cell vulvitis) are presented. One case was associated with cutaneous lupus erythematosus and another with a history of desquamative vaginitis. Two patients were postmenopausal, and two were premenopausal. The presenting symptoms were pruritus, tenderness, superficial dyspareunia and vulvar dysuria. The lesions were situated in the introitus in three patients and on the lateral aspect of the labium minus in the fourth and appeared as well-circumscribed, glistening, erythematous patches with a faint orange hue. Histologically, epidermal edema and inflammation, a dense upper dermal band of chronic inflammatory cells, including many plasma cells, dilated capillaries, extravasated red blood cells and hemosiderin deposition, were seen. There was a variable response to local steroid therapy, but one of the postmenopausal patients responded to local estrogen alone. The term vulvitis circumscripta plasmacellularis is useful to describe an idiopathic form of erosive vulvitis with a characteristic clinical and histologic appearance. PMID- 8441126 TI - Long-term control of vulval lichen sclerosus after treatment with a potent topical steroid cream. AB - Super potent topical steroids are an effective treatment for many patients with vulval lichen sclerosus, but concerns exist about their long-term safety. Review of 12 women up to 39 months following a course of super potent topical steroids shows that subsequent control of disease activity and symptoms is much easier than before therapy, with most patients requiring only small amounts of moderate potency topical steroid. Apart from a background erythema no long term cutaneous side effects were observed. PMID- 8441127 TI - Histologic parameters of vulvar invasive carcinoma and lymph node metastases. AB - We evaluated seven histologic parameters (tumor diameter, histologic grading, depth of stromal invasion, vascular invasion, pattern of invasion, lymphoplasmocytic infiltration and amount of necrosis) of 50 cases of vulvar invasive carcinoma to assess their correlation with groin lymph node metastases. Of 50 patients, 25 had groin lymph node metastases. No lymph node metastasis was found in four cases with depth of invasion < or = 2.0 mm. Among the 31 patients with vascular invasion, 23 (74%) had positive nodes, whereas lymph nodes were metastatic only in two of the 19 patients (10%) without vascular invasion. At univariate analysis, performed with Fisher's exact method, all the parameters considered, except pattern of invasion and amount of necrosis, were significantly associated (P < .05) with lymph node metastases. However, after adjustment by multiple logistic regression for the variables statistically significant at univariate level, only the presence of vascular invasion was significantly associated with nodal involvement and tumor diameter was borderline, whereas the effect of the other variables was almost completely explained by confounding. PMID- 8441128 TI - Neuroma of the vulva. A case report. AB - Even in the definitive textbook on vulvar conditions edited by Ridley no description of neuroma of the vulva exists, although neural tumors and neurofibroma are considered. The medical literature covering the past 25 years records only one case of terminal fiber neuroma in an episiotomy scar and one neuroma of the clitoris. The latter occurred in a patient with neurofibromatosis. This report documents a symptomatic neuroma of the labia minora considered to be the result of a vulval injury. It is postulated that dyspareunia related to episiotomy may be associated with disorganized proliferation of proximal nerve stumps. Because of the rarity and lack of expertise on management of vulval neuroma, we suggest that the International Society for the Study of Vulvar Disease (ISSVD) further investigate this condition. PMID- 8441129 TI - Clinical and histologic effects of topical treatments of vulval lichen sclerosus. A critical evaluation. AB - A randomized study was conducted on 79 patients with vulval lichen sclerosus who were treated for three months with four topical drugs including testosterone (2%), progesterone (2%), clobetasol propionate (.05%) and a cream based preparation. To evaluate the efficacy of the treatments, patients were examined before and after therapy for symptoms, gross appearance of the lesions and histopathologic features. Patients treated with clobetasol had a better response than responses recorded in the other groups. Remission of symptoms occurred in 75% of patients treated with clobetasol compared to 20% treated with testosterone, 10% treated with progesterone and 10% treated with a cream based preparation. The clobetasol group was the only group with gross changes and histologic evaluations before and after treatment, that showed a highly significant difference (P < .001). In a condition characterized by epidermal atrophy, we observed a significant reduction in epidermal atrophy after treatment. This study suggests that clobetasol propionate (.05%) (a very potent topical steroid) is the therapy of choice in vulval lichen sclerosus. PMID- 8441130 TI - Prevalence of Candida albicans in vaginal fluid of asymptomatic Portuguese women. AB - Candida albicans is by far the most frequent agent of genital candidosis. We studied the prevalence of C albicans in normal asymptomatic women attending primary health care centers throughout Portugal. The overall prevalence of C albicans in the vaginal fluid of 1,004 women studied was 10.4%. Interestingly, the prevalence rates were lower (6.8%) in women taking combination oral contraceptives and higher (13.0%) in those using intrauterine devices. PMID- 8441131 TI - Minimal and mild endometriosis. Is there anything new under the sun? AB - Research on endometriosis in patients with minimal or mild lesions is marred by our ignorance of the prevalence of limited stages in the asymptomatic female population of reproductive age. Laparoscopic studies performed on women undergoing tubal sterilization suggest that 2-8% are affected. However, the estimates may be unreliable because the studies were retrospective and misdiagnosis of subtle endometriosis cannot be excluded. In a recent prospective study of 86 asymptomatic women, more than 40% had minimal or mild lesions at laparoscopy. The data available do not support the suggestion that limited forms must always be treated to prevent disease progression, nor do they demonstrate worsening in all cases of minimal and mild endometriosis. Furthermore, there is no definitive evidence that the medical and surgical cytoreductive treatments available are effective in preventing eventual progression of the disease in some of the patients. We still do not know the prevalence of minimal and mild endometriosis in the healthy population, the percentage of progression towards severe stages or the risk factors of evolution of the disease. The hypothesis to test is that minimal endometriosis is partly a paraphysiologic condition that is frequently self-limited or resolves spontaneously. PMID- 8441132 TI - Benign vulvar melanosis. AB - Large melanotic lesions of the vulva are uncommon, but they may present a diagnostic problem. Eleven cases of benign vulvar melanosis are reported. The clinical features, histologic characteristics and differential diagnosis are described and analyzed. PMID- 8441133 TI - Laparoscopic versus clinical diagnosis of acute pelvic inflammatory disease. AB - The purpose of this study was to evaluate the accuracy of clinical diagnosis of acute pelvic inflammatory disease (PID). Data were obtained on 176 consecutive women admitted to St. Elizabeth Hospital Medical Center with a clinical diagnosis of PID. All underwent diagnostic laparoscopy. PID was established laparoscopically in 134 (76.1%) of the patients. Statistical tests for significant associations between PID and each of 21 clinical indicators of the disease were conducted using the chi 2 and Mann-Whitney tests. Stepwise logistic regression was performed on those variables whose univariate tests of significant association with PID resulted in P values < 0.20. An optimal set of PID indicators consisted of adnexal tenderness, lower abdominal pain of < one week's duration and an elevated white blood cell count. Use of these indicators resulted in a test with an estimated sensitivity and specificity of 86.6% and 45.7%, respectively. Estimated predictive values for positive and negative test results were 0.84 and 0.52, respectively. These results confirm the fact that laparoscopy is the definitive diagnostic modality in PID. PMID- 8441134 TI - Hematocolpometra presenting as urinary retention. A case report. AB - Acute urinary retention is a symptom that often accompanies hematocolpometra. The imperforate hymen is a rare gynecologic abnormality that can be easily diagnosed on initial presentation. We report on a 14-year-old white girl with hematocolpometra and imperforate hymen. The symptoms, operative findings and postoperative involution of internal genitalia are described. PMID- 8441135 TI - Conservative management of bilateral massive edema of the ovary. A case report. AB - A case of bilateral massive ovarian edema with unilateral ovarian torsion is reported. Following surgical removal of the adnexa with the torsion, the edema of the opposite ovary resolved with oral contraceptive therapy. This has not been previously reported. This case is instructive because the nodular appearance and yellow color of the ovaries and the presence of yellow ascitic fluid could lead to an erroneous diagnosis of malignancy, resulting in performance of a more radical surgical procedure than is necessary. A review of the literature and the unusual nature of this lesion indicates the need for caution in diagnosis and management. PMID- 8441136 TI - Dysesthetic ("essential") vulvodynia. Treatment with amitriptyline. AB - Twenty patients with chronic vulvar burning (vulvodynia) who had relief of symptoms only after treatment with low-dose amitriptyline were studied retrospectively. These patients had several factors in common, which suggested a possible neurologic component to their symptoms. The dosage of amitriptyline (initiated at 10 mg, gradually increased to 40-60 mg daily) was not sufficient to treat depression, but was in the range effective for other cutaneous dysesthesias. This study defines dysesthetic ("essential") vulvodynia, and describes a typical profile and symptom pattern for patients most likely to respond to treatment with amitriptyline (an average age of 66 with vulvodynia for three years). Dysesthetic vulvodynia appears to be a subset different from vulvar vestibulitis and other types of vulvodynia that are less responsive to treatment with tricyclic antidepressants. PMID- 8441137 TI - Erythermalgia, erythromelalgia, or both? Conditions neglected by rheumatologists. PMID- 8441138 TI - Early lesions of the articular surface in a strain of mice with very high incidence of spontaneous osteoarthritic-like lesions. AB - Our study was designed to see if the lesions of the articular surface represent an early event in the development of some types of articular degeneration. We examined the ultrastructural appearance of the articular surface labelled in vitro with cationized ferritin in several age groups of a substrain of C57BL/6 mice that develop a high incidence of osteoarthritic-like lesions. We found that as early as the age of 2 1/2 months the articular femoral and patellar surfaces presented abnormalities that became more severe with age. Alterations of the articular surface is a precocious event in this type of osteoarthritic-like degeneration. PMID- 8441139 TI - Comparison of triamcinolone acetonide with indomethacin in the treatment of acute gouty arthritis. AB - Twenty-seven patients presenting within 5 days of the onset of crystalline proven acute gout were prospectively treated with either indomethacin 50 mg tid or triamcinolone acetonide 60 mg intramuscularly. Patients with contraindications to therapy with indomethacin received triamcinolone acetonide. They were followed for 30 days. Resolution of all symptoms occurred at an average of 8 days for the indomethacin patients and 7 days in the triamcinolone patients. No side effects or episodes of rebound gout attacks occurred with the triamcinolone acetonide therapy. It is as safe and effective as indomethacin in the treatment of acute gout, and is particularly useful in patients with contraindications to therapy with nonsteroidal antiinflammatory drugs. PMID- 8441141 TI - Predicting remission in juvenile rheumatoid arthritis with methotrexate treatment. AB - Forty-nine children with a polyarticular course of juvenile rheumatoid arthritis treated with methotrexate (MTX) for at least one year were analyzed to identify clinical characteristics that would predict remission of arthritis after MTX treatment. Twenty-two children (45%) had remission of arthritis after a mean of 13.6 months of treatment and did not differ from the 27 with persistently active arthritis regarding years of disease before starting MTX, age starting MTX, maximum MTX dose, disease onset type, presence of radiographic joint destruction, concomitant treatment with hydroxychloroquine, sulfasalazine or prednisone, or presence of rheumatoid factor or antinuclear antibodies. Higher dose MTX, earlier treatment, genetic markers, and a standardized route of therapy may yield important information in future studies. PMID- 8441140 TI - Complement activation and immune complexes in juvenile rheumatoid arthritis. AB - We investigated the potential role of the complement system in juvenile rheumatoid arthritis (JRA) by examining plasma for levels of complement activation fragments C4d and Bb. We correlated findings with both disease activity and laboratory abnormalities, including immune complex (IC) levels. While there was a strong correlation between active disease and both C4d and Bb plasma levels in JRA, no strong correlations could be made between IC levels and complement activation products; weak associations were seen between complement activation fragments and erythrocyte sedimentation rate. Our data suggest that plasma complement activation is a concomitant of active disease in JRA; however, its role in the pathophysiology of JRA remains uncertain. PMID- 8441142 TI - Abnormalities in bone marrow mononuclear cells in patients with rheumatoid arthritis. AB - We analyzed the cell surface phenotype and the function of mononuclear cells in peripheral blood and in bone marrow of patients with rheumatoid arthritis (RA). The monoclonal antibodies anti-CD45RA, anti-CD29 and anti-S6F1 identify the suppressor-inducer (CD4+CD45RA+), helper-inducer (CD4+CD29+) and killer-effector (CD8+S6F1+) subpopulations of lymphocytes, respectively. In patients with RA, peripheral blood samples showed the same percentage of CD4+CD45RA+, CD4+CD29+ and CD8+S6F1+ cells as seen in control subjects. In contrast, in the bone marrow of patients with RA we observed a significant decrease in CD4+CD45RA+ cells, a significant increase in CD8+S6F1+ cells compared with findings in peripheral blood and in bone marrow samples from control subjects. Consistent with the phenotypic changes observed, bone marrow T cells also showed functional abnormalities, since autologous mixed lymphocyte reaction-activated CD4 cells from bone marrow of patients with RA showed a decrease in suppressor-inducer activity and CD8+ cells activated by allogenic E- cell showed an increase in killer-inducer activity. The changes noted above may contribute to the immunologic abnormalities that occur in this disease and provide insight into the pathophysiology of RA. PMID- 8441143 TI - Glycosylation of alpha 1-acid glycoprotein in systemic onset juvenile rheumatoid arthritis and acute bacterial infection: value in differential diagnosis. AB - Agarose based affinity immunoelectrophoresis with free concanavalin A (Con-A) as ligand was used to examine the microheterogeneity of alpha 1-acid glycoprotein in sera of patients with systemic onset juvenile rheumatoid arthritis (JRA) and acute bacterial infections. In JRA, a decreased proportion of Con-A reactive alpha 1-acid glycoprotein variants was found when compared to healthy control. In contrast, acute bacterial infection showed an increased reactivity. Investigation of glycosylation may be useful in the differential diagnosis of systemic onset JRA and acute bacterial infection. PMID- 8441144 TI - Eosinophilic fasciitis in children frequently progresses to scleroderma-like cutaneous fibrosis. AB - We evaluated longterm outcome in 21 pediatric patients with biopsy proven eosinophilic fasciitis (EF), 4 followed in our rheumatology clinic and 17 reported in the literature. Two-thirds of these patients developed residual cutaneous fibrosis, while one-third enjoyed complete resolution of disease. Children under age 7 years were twice as likely as those over age 7 years to experience disease progression to cutaneous fibrosis [relative risk = 2.0 (95% confidence intervals 1.2, 3.4)]. Fourteen of 17 patients with extensive disease at diagnosis (involvement of 3-4 extremities +/- trunk) progressed to cutaneous fibrosis whereas all 4 patients with minimal disease (involvement of 1-2 extremities) at onset resolved completely. We detected no association between progression to cutaneous fibrosis and sex of patient, duration of symptoms prior to therapy, type of therapy, history of prior physical stress, or laboratory variables at diagnosis. PMID- 8441145 TI - Mucolipidosis III presenting as a rheumatological disorder. AB - Genetic disorders of the osseous skeleton constitute a challenging area of differential diagnosis. Three patients, 2 girls and 1 boy, were referred to our pediatric rheumatology clinic because of progressive stiffness of their hands and flexion contractures of fingers, accompanied by additional musculoskeletal changes. One of the girls had been diagnosed in early childhood as having juvenile rheumatoid arthritis, the other was suspected to have scleroderma, and the boy had been labelled with "Hurler's syndrome." On evaluation, all 3 patients had the clinical and roentgenographic features of mucolipidosis III; the diagnosis of mucolipidosis III was confirmed by enzymatic assays. We call for an awareness of pediatricians, rheumatologists and orthopedic surgeons to the "rheumatological" presentation of mucolipidosis III. The establishment of a precise diagnosis will lead to adequate management and will allow appropriate genetic counseling. PMID- 8441146 TI - Apparent cure of rheumatoid arthritis by bone marrow transplantation. AB - We describe the induction of sustained remissions and possible cure of severe erosive rheumatoid arthritis (RA) by bone marrow transplantation (BMT) in 2 patients. BMT was used to treat severe aplastic anemia which was caused by gold in one case and D-penicillamine in the other. In the 8 and 6 years since the transplants (representing 8 and 4 years since cessation of all immunosuppressive therapy, respectively), the RA in each case has been completely quiescent. Although short term remission of severe RA following BMT has been reported, these are the first cases for which prolonged followup has been available. This experience raises the question of the role of BMT itself as a therapeutic option for patients with uncontrolled destructive synovitis. PMID- 8441147 TI - Rheumatoid arthritis associated with myositis and anti-Jo-1 antibody. PMID- 8441148 TI - Secondary erythermalgia in systemic lupus erythematosus; [comment]. AB - Secondary erythermalgia, as a symptom of an underlying illness, is characterized by burning pain in the extremities together with local erythema and warmth. The onset and clinical symptomatology of secondary erythermalgia in a woman with a 20 year history of systemic lupus erythematosus (SLE) is described. Histopathologic examination of affected skin areas revealed an inflammatory process compatible with vasculitis. These findings completely differ from the histopathology in erythromelalgia and in primary erythermalgia. The erythermalgic symptoms completely resolved by treatment with prednisone. We conclude that secondary erythermalgia in SLE in our patient was associated with cutaneous vasculitis. PMID- 8441149 TI - Mixed connective tissue disease associated with lupus lymphadenitis. AB - We have encountered 2 patients with mixed connective tissue disease (MCTD) associated with lymphadenopathy at the outset. Biopsy specimens of enlarged lymph nodes showed massive necrotizing lesions with follicular hyperplasia, which are occasionally observed in the involved lymph nodes of patients with systemic lupus erythematosus (SLE) and called lupus lymphadenitis. Usually, the only histologic finding of an involved lymph node in MCTD is lymphoid hyperplasia. These are the 2nd and 3rd cases of MCTD associated with lupus lymphadenitis. Our cases suggest that histologic studies of the swollen lymph nodes are not helpful in distinguishing MCTD from SLE. PMID- 8441150 TI - Duodenal hemorrhage and dermal vasculitis associated with mixed connective tissue disease. AB - We describe a 23-year-old woman with mixed connective tissue disease (MCTD) who developed duodenal bleeding responsive to treatment with corticosteroid and recurrent skin eruptions due to leukocytoclastic vasculitis. The endoscopic findings revealed patchy, reddened, edematous, friable mucosa with scattered small ulcers and oozing of blood in the second portion of the duodenum. Endoscopic pictures from the onset to healing are presented. This appears to be the first recorded occurrence of such findings in MCTD. PMID- 8441151 TI - Reflex sympathetic dystrophy syndrome and osteogenesis imperfecta. A report and review of the literature. AB - A case of multifocal reflex sympathetic dystrophy (RSDS) in a patient with the tarda form of osteogenesis imperfecta is described, followed by a review of the literature. Microfractures of the trabecular bone in these patients are proposed to be the initial stimulus in the pathogenesis of RSDS by a mechanism similar to the one involved in the pathogenesis of RSDS complicating other diseases associated with bone fragility. PMID- 8441152 TI - Reflex sympathetic dystrophy involving multiple extremities. AB - We describe a patient with 4 episodes of reflex sympathetic dystrophy involving 3 limbs occurring over a 4-year period of time. The patient did not respond to steroids but responded well to either sympathetic blocks or sympathectomy. PMID- 8441153 TI - Delayed type hypersensitivity in patients with rheumatoid arthritis. AB - Our study examines the relationship between in vivo delayed type hypersensitivity (DTH) and clinical and laboratory variables associated with rheumatoid arthritis (RA). Eleven patients with RA were examined. They were receiving no disease modifying drugs, immunosuppressive agents or corticosteroids. Skin tests were performed with the Multitest CMI system employing 7 antigens simultaneously. No patients were truly anergic, however, 3 of the 11 patients were hyporesponsive. No difference was noted between the total in vivo DTH responses of the patient and control populations. A significant correlation was observed between total DTH and the overall activity of the RA as measured by the erythrocyte sedimentation rate (ESR). However, there was no relationship between the total DTH scores and the degree of synovitis. There was no correlation between DTH and a variety of laboratory variables including the autologous mixed lymphocyte response, and the percentage of activated CD4+ or CD8+ T lymphocytes. These observations indicate that while anergy was uncommon in our population of patients with RA, decreased DTH responses were associated with greater disease activity as determined by the ESR. PMID- 8441154 TI - Two cases of spondylometaphyseal dysplasia. Literature review and discussion of the genetic inheritance of the disease. AB - We describe 2 cases of spondylometaphyseal dysplasia: in a 33-year-old woman and her 42-year-old stepsister. The usual pattern of inheritance is autosomal dominant. As this was not so in our cases, we offer another explanation. PMID- 8441155 TI - Effect of early synovectomy on the course of rheumatoid arthritis. PMID- 8441156 TI - Antituberculous drugs in rheumatoid arthritis. PMID- 8441157 TI - Non-Hodgkin's lymphoma, rheumatoid arthritis and methotrexate. PMID- 8441158 TI - Sjogren's syndrome associated with CREST and positive antibodies to Ro(SSA)/La(SSB) PMID- 8441159 TI - Prevalence of pericardial effusion by echocardiography in juvenile rheumatoid arthritis. PMID- 8441160 TI - Validity and reliability of the timed-stands test for patients with rheumatoid arthritis and other chronic diseases. AB - The timed-stands test (TST) is a simple measure of lower extremity strength which correlates with age in healthy people. We validated the TST as a functional assessment tool against other measurements of functional capacity and comorbidity in 147 patients with rheumatoid arthritis (RA) or other chronic diseases. The TST was significantly impacted by RA disease activity and by comorbidity. Age affected TST only in patients without arthritis or life threatening disease. TST is a simple, reproducible measure of lower extremity function that was valid in this patient population. PMID- 8441161 TI - Evaluation of the Thompson articular index. AB - Three articular indices for measuring disease activity are compared. In a cross sectional study the Thompson articular index (a modified Lansbury index) correlated better with laboratory variables than the Ritchie articular index or a swollen joint score (Thompson 0.74-0.77; Ritchie 0.57-0.58; swollen joint count 0.51-0.59). In a longitudinal study it was shown that the Thompson articular index is sensitive to detect changes of disease activity. We suggest that this index is appropriate for clinical trials. PMID- 8441162 TI - Which clinical variables contribute to the physician's assessment of medium term outcome in rheumatoid arthritis? AB - To investigate the clinical variables that contribute to the physician's opinion of the medium term outcome of rheumatoid arthritis (RA), we compared the physician's opinion with statistical modelling of these clinical variables. In 133 young female patients with RA followed yearly (mean followup duration 6 years) from symptom onset, the physician had to state whether the disease course was mild or progressive. Using logistic regression models we concluded that the physician's opinion could be explained by using a compilation of the erosion score, the number of swollen joints, the Ritchie score as measured at the latest visit, in combination with either the mean number of swollen joints during followup, or the number of prescribed second line drugs. Several different models with a common core were equally close to the physician's opinion. PMID- 8441163 TI - Familial amyloidosis--hereditary systemic disease of the connective tissue and other organs. PMID- 8441164 TI - Detecting treatment effects in patients with rheumatoid arthritis: the advantage of longitudinal data. AB - Assessment of therapy in patients with rheumatoid arthritis is important but difficult. We examined 4 different methods of analyzing pretreatment data and assessed the difference that each made in detecting a positive effect of intramuscular gold on the patient's overall disability. The methods were (1) calculating the arithmetic mean of prior data points, (2) taking the last data point pretreatment, (3) fitting a straight line to pretreatment points and (4) fitting the pretreatment points with a quadratic equation. After comparison with matched controls (not taking remittive agents) the most significant difference was found by fitting a straight line to pretreatment data. This technique demonstrated about one-third more of intramuscular gold's effectiveness than the usual technique of using the last data point pretreatment. We conclude that statistical power is improved by obtaining and analyzing longitudinal pretreatment data appropriately. PMID- 8441165 TI - Outcome of rheumatoid arthritis in relation to age and rheumatoid factor at diagnosis. AB - Our retrospective followup study reports the outcome of rheumatoid arthritis (RA) in relation to age (under 60 vs 60 years and over) and rheumatoid factor status at diagnosis. A sample of 130 adult patients with RA was assessed at a mean of 5.6 years after diagnosis. At final evaluation disease activity and radiographic damage in seropositive patients were similar in both age groups, but functional capacity was markedly lower in the older onset group, indicating lower functional reserves in this group. In seronegative patients the outcome was favorable in both age groups, especially in the older patients. Seropositive patients in both age groups had more disease activity, a lower functional capacity and more radiographic damage than seronegative patients; these differences were greater in the older onset patients. The mortality in patients with RA compared to the general population (standardized mortality ratio, SMR) was higher in seropositive patients (SMR 2.78, 95% CI 1.70-4.13) but not in seronegative patients (SMR 0.45, 95% CI 0.08-1.13). The relative risk of dying was 6 times higher in seropositive patients than in seronegative patients (95% CI 1.7-20.9). PMID- 8441166 TI - IgA anti-dsDNA antibodies in systemic lupus erythematosus: occurrence, incidence and association with clinical and laboratory variables of disease activity. AB - The relationship between IgA anti-dsDNA antibodies and systemic lupus erythematosus (SLE) disease activity was investigated. IgA anti-dsDNA antibodies were measured using ELISA techniques. Elevated serum levels of IgA anti-dsDNA antibodies were detected in 51% of the patients with SLE (n = 57) and 8% of the diseased controls (n = 214). The presence of IgA anti-dsDNA antibodies was associated with kidney and joint abnormalities, with hypocomplementemia and with circulating immune complexes. We conclude that increased levels of IgA anti-dsDNA antibodies are associated with disease activity in patients with SLE. PMID- 8441167 TI - The longterm prognosis of lupus nephritis: the impact of disease activity. AB - An inception cohort of 87 patients with lupus nephritis was evaluated using a classification tree regression technique. Four relevant outcomes were studied: (1) renal insufficiency (serum creatinine > 5.0 mg/dl); (2) renal failure; (3) death due to renal involvement; and (4) any death due to systemic lupus erythematosus. All 4 outcomes could be predicted by one or more renal severity measures (serum creatinine, 24-h urinary protein excretion, nephrotic syndrome, or duration of prior renal disease), and among those with nonsevere renal disease, with a single disease activity measure (the National Institutes of Health or le Riche index). In general 3 prognostic groups (high, intermediate and low risk) could be identified for each outcome. Our results demonstrate the value of regression tree techniques in studies of prognosis and are compatible with a hypothesis of the interaction of disease activity with organ damage in lupus nephritis. PMID- 8441168 TI - Prevalence of Raynaud's phenomenon in a healthy Spanish population. AB - To determine the prevalence of Raynaud's phenomenon (RP) in Spain, we studied a working population of 988 men and 479 women. The overall prevalence of RP was 3.7%, with a 3.2% rate for men and 4.7% for women. There was a statistically significant association between Raynaud's phenomenon and a personal or familial history of perniosis, acrocyanosis or migraine among women. The age at onset was significantly lower in women. RP was classified as primary in 89% of the cases and as secondary in 11%. Examination by capillaroscopy revealed no significant differences between primary Raynaud cases and controls. PMID- 8441169 TI - Induction of arthritis in DA rats by incomplete Freund's adjuvant. AB - OBJECTIVE: To define the arthritogenic effects of incomplete Freund's adjuvant (ICFA) injections in DA rats. METHODS: ICFA was injected into DA rats and other inbred rat strains. The severity of arthritis was scored and associated changes in weight recorded. RESULTS: After ICFA injection a mild transient symmetric arthritis developed in 15/22 (68%) of the DA rats observed for greater than 4 weeks. Histologic examination of the observed arthritis showed edema and neutrophil infiltrates with some lymphocytes and plasma cells. No arthritis developed in DA rats given normal saline injections nor in Lewis, DA.1N and WF.1N rats given ICFA. CONCLUSIONS: Injection of DA rats with ICFA alone can produce arthritis. PMID- 8441170 TI - Geographic variation in the prevalence of Raynaud's phenomenon: Charleston, SC, USA, vs Tarentaise, Savoie, France. AB - We estimated the prevalence of Raynaud's phenomenon (RP) in the general population of 2 geographic areas, Charleston County, South Carolina, USA, and Tarentaise, Savoie, France, using the same methodology in both countries. The first phase of the study, consisting of the telephone survey of a randomly drawn sample of households, yielded 2086 completed interviews in Charleston and 2000 in Tarentaise. Cold sensitivity or unusual digital color changes were reported by 17.9% of the subjects in Charleston and by 31.3% in Tarentaise. In the second phase of the study the diagnosis of RP was made by a medical team. Based on these results, the estimated prevalence of RP is 5.0% (0.8% SE) in Charleston (women 5.7%, men 4.3%) and 16.8% (2.0% SE) in Tarentaise (women 20.1%, men 13.5%). PMID- 8441171 TI - HLA-DP positive T cells in patients with polymyositis/dermatomyositis. AB - The examination of HLA-DP+ T cells in 21 patients with polymyositis/dermatomyositis revealed marked increases [28.5% (SD 16.6%)], compared with the HLA-DQ+ and DR+ T cells. The HLA-DP molecule was expressed on both CD4+ and CD8+ T cells. The majority of HLA-DP+ CD8+ cells were cytotoxic T cells. There was no significant correlation between the proportion of HLA-DP+ T cells and the level of myogenic enzyme, although a decrease in HLA-DP+ T cells after therapy was accompanied by a decrease in myogenic enzymes. However, the proportion of HLA-DP+ CD8+ cells was significantly higher in those patients with active pneumonitis. PMID- 8441172 TI - Therapeutic strategies distinguish community based primary care physicians from rheumatologists in the management of osteoarthritis. AB - Using an osteoarthritis (OA) case study, we described the drug therapy that primary care physicians prescribe for uncomplicated OA of the hip, and for OA complicated by a history of gastropathy or renal insufficiency. To produce "gold standard" criteria against which to interpret previous results, the same instrument was administered to 126 rheumatologists selected at random from the membership of the American College of Rheumatology. Virtually all rheumatologists prescribed nonsteroidal antiinflammatory drugs (NSAID); 76% specified doses large enough to have significant antiinflammatory effects. In contrast, 65% of the primary care physicians recommended NSAID therapy in a suboptimal antiinflammatory dose (p = 0.055 for the rheumatologist-primary care physician difference). For OA complicated by a history of either gastropathy or renal insufficiency, rheumatologists were more likely than primary care physicians to adopt a therapeutic strategy that did not inhibit prostaglandin synthesis (p < 0.001 for both). Differences also were noted in the ancillary therapies employed by the 2 groups for managing uncomplicated OA. Educational interactions between rheumatologists and primary care physicians could benefit by recognition of the differing perspectives on NSAID dosing, the avoidance of NSAID induced side effects, and ancillary therapies that appear to differentiate subspecialists and generalists. PMID- 8441173 TI - Hyaluronate in total hip replacement. AB - We studied the composition of the fluid in joint cavity of the hip joint in primary osteoarthritis (OA) from samples obtained at primary total hip replacement (THR) operations (N = 21) and in the THR pseudojoint, where the samples were obtained in revision operations for the common type of prosthesis loosening (N = 17). Protein concentrations differed little in both groups (31.8 +/- 1.9 mg/ml vs 34.4 +/- 1.9 mg/ml, p < 0.01), which suggests similar transcapillary flow in the degenerative hip joint and THR pseudojoint. Hyaluronate was found in OA joint fluid and in the fluid from the THR pseudojoint (2.21 +/- 0.23 mg/ml vs 0.43 +/- 0.04 mg/ml, p < 0.005) and high performance liquid chromatography (HPLC) analysis, calibrated using laser light scatter analyzed molecular weight standards, disclosed the low molecular weight nature of the OA synovial fluid compared to the THR pseudojoint fluid (1.12 +/- 0.84 x 10(6) vs 2.63 +/- 1.13 x 10(6) Da, NS). This suggests that THR arthroplasties cause an adaptive tissue response and formation of fibroblast-like B type lining cells able to synthesize and secrete hyaluronate. PMID- 8441174 TI - Plasminogen activators and plasminogen activator inhibitors in synovial fluid. Difference between inflammatory joint disorders and osteoarthritis. AB - The plasminogen activator (PA)/plasminogen activator inhibitor (PAI) system is believed to be involved in connective tissue remodelling in joint disease and both PA and PAI production has been shown in several cell types in the joint. We quantified immunoreactive PA and PAI in synovial fluid (SF) and correlated their levels to levels of cartilage derived proteoglycans, radiologically visible joint involvement and to signs of local inflammation. PAI-2 concentrations were increased, compared to normal plasma levels, in patients with rheumatoid arthritis (RA) and reactive arthritis, but not in patients with osteoarthritis (OA). Thirty percent of the patients with RA, but no patient with OA had increased concentrations of PAI-1. Increased concentrations of urokinase type PA (u-PA) were found in RA but not in OA. Tissue type PA (t-PA) concentrations were low in both disease groups. SF proteoglycan concentrations did not correlate with levels of PA or PAI. Concentrations of PAI-2 correlated significantly with SF leukocyte count and cytidine deaminase (CD) activity and u-PA concentrations correlated with CD activity. Both PAI-2 and u-PA were detected in supernatants from lysed polymorphonuclear cells. This suggests that in addition to release from synovial cells and chondrocytes these components may also be released from polymorphonuclear cells. Our results support a pathophysiological role for the fibrinolytic system in joint disease, possibly more pronounced in inflammatory disorders than in OA. PMID- 8441175 TI - Anomalously slow mobility of fluorescent lipid probes in the plasma membrane of the yeast Saccharomyces cerevisiae. AB - We measured the lateral mobility of two fluorescent lipid probes dioctadecylindocarbocyanine (diI) and tetramethyl rhodamine phosphatidylethanolamine (R-PE) in the plasma membranes of Saccharomyces cerevisiae ino1 and opi3 spheroplasts. These are well-characterized strains with mutations in the inositol and phosphatidylcholine biosynthetic pathways. Membrane phospholipid composition was altered by growing these mutants in the presence or absence of inositol and choline. Lateral mobility was measured by fluorescence recovery after photobleaching (FRAP). Microscopic fluorescence polarization employing CCD digital imaging produced an ordered orientation distribution of the lipid probe diI, confirming that at least one of the probes was largely incorporated into the bilayer membrane. Our results demonstrated anomalously slow mobility of both lipid probes for both mutants, regardless of whether the lipid composition was near normal or dramatically altered in relative composition of phosphatidylinositol and phosphatidylcholine. Trypsinization of the spheroplasts to remove surface proteins resulted in markedly increased lateral mobility. However, even in trypsinized spheroplasts, mobility was still somewhat lower than the mobility observed in the membrane of mammalian cells, such as rat smooth muscle culture cells tested here for comparison. PMID- 8441176 TI - Failure of chronic, high-dose, oral vitamin E treatment to protect the ischemic, reperfused porcine heart. AB - Lipid peroxidation, presumably the result of free radical-mediated injury, has been shown to occur during myocardial ischemia and reperfusion. Since vitamin E is a very effective, naturally occurring, chain-breaking antioxidant, it was investigated whether a vitamin E-supplemented diet increased myocardial tolerance towards ischemia and reperfusion in pigs. In addition to a standard diet which contained 30 mg vitamin E/kg (approximately daily vitamin E intake 30 mg), ten pigs were fed with 10 g vitamin E (all-rac-alpha-tocopherol acetate, Merck AG, Darmstadt, Germany) daily for at least 4 weeks. Ten control pigs remained on the standard diet. In an open chest preparation, the left anterior descending coronary artery was distally ligated for 45 min followed by 3 d of reperfusion. Infarct size was determined as the ratio of infarcted (tetrazolium stain) to ischemic myocardium (dye technique). Regional systolic shortening was evaluated by sonomicrometry. Vitamin E concentrations in plasma and myocardium were measured by high-performance liquid chromatography. Global hemodynamic characteristics did not differ between the two groups. Oral pretreatment with vitamin E raised the plasma concentration of this vitamin from 1.1 +/- 0.3 to 5.0 +/- 1.0 mg/l and the myocardial content from 4.2 +/- 0.7 to 18.6 +/- 2.7 ng/mg fresh weight. Vitamin E treatment did not reduce infarct size, which amounted to 71.3 +/- 5% in the control group and to 71.7 +/- 8.2% in the treated animals. Furthermore, recovery of regional systolic shortening of the reperfused segment did not significantly differ in the two groups after 3 d of reperfusion; it measured 2 +/- 4% in the controls and 6 +/- 6% (p = 0.16) in the treated animals. Therefore, chronic, oral treatment with vitamin E which raised myocardial and plasma concentrations of this vitamin 4- to 5-fold did not increase myocardial tolerance towards ischemia and reperfusion in this animal model. PMID- 8441177 TI - Circulating alpha-actin in angina pectoris. AB - We used Western blot, a highly sensitive technique that detects amounts of protein as low as 0.1 to 1.0 ng, to investigate the possible presence in the blood stream of the contractile protein alpha-actin in 29 patients diagnosed with angina pectoris (Braunwald's classification). Circulating protein was identified with a monoclonal antibody specific for cardiac alpha-actin. Of the 20 control samples of blood, the immunoblot results were negative for alpha-actin in 19. Of the 30 patients with skeletal muscle damage caused by surgery, 27 were negative for circulating alpha-actin. Of the 29 patients with angina pectoris, circulating alpha-actin was found in 19 as a 43 kDa band in immunoblots. Of the four patients with anterior acute myocardial infarction, mean concentration of circulating alpha-actin was 58 mg/l. Among the patients with angina pectoris, the highest circulating concentrations (mean 40 mg/l) was found in those with prolonged angina (class III B, according to Braunwald's classification). In the entire group of individuals with angina pectoris alpha-actin was detectable in serum for up to 175 h after the onset of pain, and showed two peaks, one at 1 h (112 mg/l) and one at 50 h (82 mg/l) after the onset of pain. These findings reinforce the notion that unstable angina should be considered a serious condition. PMID- 8441178 TI - The effect of thapsigargin on sarcoplasmic reticulum Ca2+ content and contractions in single myocytes of guinea-pig heart. AB - Contractures initiated by 1 s superfusion of single myocytes of guinea-pig heart with 10 mM caffeine were used as a relative index of the SR Ca2+ content. Thapsigargin (Tg) in concentration 2 x 10(-7) M completely blocked Ca2+ uptake during electrical stimulation by the SR from which Ca2+ has been previously depleted by caffeine. Tg did not affect the SR Ca2+ content in the resting myocytes and did not block release of the SR Ca2+ during electrically stimulated contractions (ESCs). It is concluded that in guinea-pig myocytes Tg affects SR Ca2+ by selective blocking the SR Ca2+ uptake. The amplitude of steady state ESCs dropped to 68 +/- 5.4% (S.D., n = 20) of that of the pre-Tg control. Time to peak contraction increased from 454 +/- 82.4 ms to 820 +/- 157.4 ms and time of relaxation increased from 368 +/- 90.8 ms to 474 +/- 87 ms after the SR Ca2+ has been depleted by Tg. Rest decay of contractions, post-extrasystolic potentiation and post-rest potentiation were inhibited. PMID- 8441179 TI - Coronary dilator reserve and morphological changes after relief of pressure overload in rats. AB - Using a rat model of short- (4 weeks) and long-term (10 weeks) ascending aortic banding and debanding, we examined the relationship between coronary dilator reserve and morphological vascular changes. After 4 or 10-week banding, in vivo systolic left ventricular pressure and ventricular wt/body wt ratio increased to a similar level, compared with controls. The coronary dilator reserve measured in an isolated heart preparation decreased similarly in the two banded groups, compared with controls. The ratios of medial to luminal area and perivascular collagen to luminal area in coronary microvessels increased in the banded groups. At 4 weeks after debanding, cardiac hypertrophy regressed to the control level, and the duration of banding did not alter the extent of the regression. The coronary dilator reserve normalized in the group debanded after 4-week banding, but did not regress in the group debanded after 10-week banding. In both of the debanded groups, the hypertrophied media regressed completely. The increased perivascular collagen regressed almost completely in the group debanded after 4 week banding, but remained greater in the group debanded after 10-week banding than in the controls. From these results, we conclude that (i) the regression of medial hypertrophy does not always improve the decreased coronary dilator reserve, and (ii) the vascular fibrosis may be the major cause of the irreversibility of decreased coronary dilator reserve in long-term cardiac hypertrophy. PMID- 8441180 TI - Toxic oxygen metabolites and ischemia-reperfusion increase histamine synthesis and release in the isolated rat heart. AB - Histamine is synthetized in the heart, and released by ischemia-reperfusion injury in several species. Histamine has arrhythmogenic, chronotropic, inotropic and vasoactive effects. Cardiac histamine release during ischemia-reperfusion may be mediated by toxic oxygen metabolites. We studied the effect of ischemia reperfusion and toxic oxygen metabolites on release and synthesis of histamine in the isolated rat heart (Langendorff model). The following groups were included: I, (n = 10) control perfusion for 60 min; II, (n = 7) H2O2 (200 microM) was given for 10 min followed by 50 min recovery; III, (n = 7) thiourea (15 mM) was given in addition to H2O2; IV, (n = 7) thiourea given alone; V, (n = 7) catalase (150 U/ml) plus H2O2; VI, (n = 7) 20 min ischemia followed by 40 min reperfusion. The contents of histamine in the coronary effluent and in cardiac tissue were measured repeatedly (radioenzymatic method). Ischemia-reperfusion and toxic oxygen metabolites increased release of histamine in the coronary effluent. Concomitantly the histamine contents in cardiac tissue increased, indicating increased synthesis of histamine. PMID- 8441181 TI - Protein kinase C phosphorylation of cardiac troponin I and troponin T inhibits Ca(2+)-stimulated MgATPase activity in reconstituted actomyosin and isolated myofibrils, and decreases actin-myosin interactions. AB - The inhibitory effects of the phosphorylation of bovine cardiac troponin I (TnI) and troponin T (TnT) by protein kinase C (PKC) on the activity of Ca(2+) stimulated MgATPase of reconstituted actomyosin complex, as a function of the concentration of myosin or myosin subfragment 1 (S-1), were investigated. Phosphorylation of TnI and/or TnT invariably decreased the Ca(2+)-stimulated enzyme activity of reconstituted actomyosin or actomyosin S-1, regardless of the concentration of whole myosin or S-1. The inhibition due to phosphorylated TnI was partially overcome as the concentration of myosin or S-1 increased, suggesting simple competition of phosphorylated TnI with myosin or S-1 for actin binding sites. Inhibition due to phosphorylated TnT, however, remained constant at all concentrations of myosin or S-1, suggesting that phosphorylated TnT may inhibit full Ca(2+)-activation of the thin filament. Both phosphorylated TnI and TnT inhibited the Ca(2+)-stimulated binding of S-1.ADP to regulated actin, consistent with the notion that the effects of phosphorylation of TnI and TnT affected interactions of the thin filament with the thick filament. Effects of PKC phosphorylation of the contractile components in adult rat cardiac myofibrils were also investigated. PKC phosphorylation of TnI and TnT, as well as other proteins in the contractile complex, resulted in the inhibition of Ca(2+) stimulated MgATPase activity with little change in the Ca(2+)-sensitivity. Thus, the negative inotropic effects attributable to activation of PKC by phorbol esters, as reported by others, could be explained in part through PKC mediated phosphorylation of components of the contractile apparatus. PMID- 8441183 TI - The role of sarcoplasmic reticulum and Na-Ca exchange in the Ca2+ extrusion from the resting myocytes of guinea-pig heart: comparison with rat. AB - Inhibition of the Na-Ca exchange at the beginning of rest in isolated myocytes of the guinea-pig heart by means of superfusion with Na,Ca-free solution or 5.0 mM Ni2+ resulted in appearance of multiple phasic contractures. Contractures could not be initiated when the sarcoplasmic reticulum (SR) Ca2+ had been depleted by short (1 s) or steady state exposure to 10 mM caffeine, 0.1 microM ryanodine or due to rapid spontaneous release of the SR Ca2+ occurring sometimes at the beginning of rest. Superfusion with 2 x 10(-7) M thapsigargin, which blocked the SR Ca2+ uptake, prevented contractures otherwise initiated by superfusion with the Na,Ca-free solution. The frequency of spontaneous contractures was positively related to the rate of stimulation before rest and negatively related to the duration of rest before superfusion with the Na,Ca-free solution. It is proposed that in guinea-pig myocardium Ca2+ taken up by the SR from sarcoplasm or other cellular compartments like mitochondria, is released during diastole and rest to the subsarcolemmal space from which it is extruded by means of Na-Ca exchange. The release is a primary event not dependent on decrease of the resting sarcoplasmic free [Ca2+] by the outward Ca2+ transport. Inhibition of the Na-Ca exchange at the beginning of rest did not initiate any contractile response in rat myocytes. If the spontaneous contractures were already present, they were inhibited by superfusion with the Na,Ca-free solution. The result reflects the basic difference in the properties of SR of guinea-pig and rat. PMID- 8441182 TI - Formation and breakdown of uridine in ischemic hearts of rats and humans. AB - In contrast to cardiac purine metabolism, little is known about pyrimidine catabolism in heart. We therefore investigated uridine and uracil formation in ischemic rat and human hearts. Human donor hearts accumulated uridine 3 x (P < 0.05) before implantation. Hearts released this pyrimidine during implantation or correction of cardiac defects. During the former systemic blood uridine rose 38% (P < 0.05). In explanted human hearts, uridine was the only pyrimidine released during reperfusion; isolated, perfused rat hearts produced initially 3 x more uracil than uridine. Uridine phosphorylase activity in human heart homogenate was 3.4 mU/g wet weight, i.e. 60 x lower than that in rat myocardium (198 mU/g, P < 0.02); its purine counterpart, nucleoside phosphorylase, differed much less in activity (0.32 and 1.12 U/g, respectively; P < 0.001). Thus human heart is virtually devoid of uridine phosphorylase, contrasting rat heart. Consequently uridine accumulates in ischemic human heart while uracil production predominates in rat heart. PMID- 8441184 TI - Diabetes-related eye disorders. AB - Ocular complications from diabetes represent a significant public health problem. Diabetic retinopathy alone represents a leading cause of new blindness each year in the United States. Neovascular glaucoma from diabetes, although not nearly as common, inflicts devastating consequences on vision. Together with the more frequent occurrence of other ocular disorders that cause visual impairment, the visual toll of diabetes is staggering. Much of this blindness is preventable with early detection and timely treatment. PMID- 8441185 TI - Prostate cancer: results of external irradiation. AB - From 1975 to 1982, 205 patients with local prostate cancer were treated at the radiation oncology department, the University of Kansas Medical Center, Kansas City, Kansas. Patients' median age was 73 years. All of the patients were staged according to American Urologic staging criteria. Twenty-eight patients had stage A2 cancer, 91 patients had stage B cancer, and 86 patients had stage C cancer. All patients were treated using megavoltage radiation (dosage range: 6000 cGy to 7100 cGy). The follow-up period ranged from a minimum of 8 years to a maximum of 15 years (median: 9.4 years). The clinical local control was 96% for stage A2, 94% for stage B, and 90% for stage C disease. The overall and disease-free survival rates were 71% and 60%, respectively. Fourteen patients developed moderate complications with one patient (0.5%) requiring surgical intervention. The local control and survival rates reported in this study are comparable with surgical results, suggesting that external beam irradiation in prostate cancer is safe and effective. PMID- 8441186 TI - Sexuality and sickle cell disease. AB - Chronic illness can impact negatively on sexuality and sexual satisfaction. A group of 44 patients with sickle cell anemia and a control group of 42 individuals with no chronic illness completed the Derogatis Sexual Functioning Inventory (DSFI). The sickle cell anemia group also completed the Psychosocial Adjustment to Illness Scale--Self-Report (PAIS-SR). Cumulative scores on the PAIS SR were used to divide the sickle cell anemia group into two subgroups--those who were poorly adjusted to their illness and those who were well adjusted to their illness. Analysis of the scores showed significant differences in sexual functioning and sexual satisfaction between those in the sickle cell group who were well adjusted to their illness and those who were poorly adjusted. Of note was the fact that there was no statistically significant difference between the DSFI scores in the well adjusted group and the control group. Other significant factors included the lack of accurate sexual information in the sickle cell anemia group and the importance of satisfaction with the health-care system in total adjustment to illness. In addition, results revealed that severity of illness had little impact on adjustment to illness. PMID- 8441187 TI - The value of endocervical curettage at time of cervical cone biopsy. AB - Two hundred eighty-nine patients were evaluated over a 23-month period to assess the efficacy of postcone biopsy endocervical curettage at the time of cervical conization. One hundred eleven patients were excluded because the endocervical curettage was insufficient or not performed, the final pathology on the cone biopsy and endocervical curettage revealed no dysplasia or cancerous process, or the endocervical margins were not assessed, leaving a total of 178 patients in the study population. A negative conization endocervical margin virtually assures no disease in the upper endocervical canal. The negative predictive value in this study population was 97%. We conclude that routine endocervical curettage is unnecessary for most patients and should be primarily considered for patients who are postmenopausal or for those receiving suboptimal conizations. PMID- 8441188 TI - The relationship between maternal hematocrit and pregnancy outcome: black-white differences. AB - Racial differences in hematocrit levels and the relationship between low and high hematocrit, intrauterine growth retardation, and preterm delivery were studied in a population of 17,149 low-income, iron- and folate-supplemented pregnant women. Hematocrit levels drawn during four gestational periods were considered. Evaluating pregnancy outcome in regard to hematocrit values at specific gestational ages eliminated the bias resulting in the previously reported association between a low hematocrit and preterm delivery in blacks. In contrast, in this study, in blacks, hematocrits of 27% to 30% were associated with lower but not significant reductions in the rates of intrauterine growth retardation and preterm delivery. Our major finding was that at 31 to 34 weeks, hematocrits > or = 40% were associated with significantly higher odds ratios for intrauterine growth retardation for both blacks and whites. These findings should prompt more attention to women who have high hematocrits in pregnancy while reducing concern for women of either race with low hematocrits. PMID- 8441189 TI - Actinomycosis of the neck: diagnosis by fine-needle aspiration biopsy. AB - A patient with actinomyces infection of the posterior neck was diagnosed by fine needle aspiration biopsy. The lesion presented as a recurrent, firm, and indurated mass that was clinically diagnosed as adenitis and cellulitis and was thought to be a lymphoma 6 months after the onset of his illness. Smears and cell block sections of the aspirate showed characteristic colonies ("sulfur granules") of actinomyces. Subsequent regional lymph node biopsy revealed reactive lymphoid hyperplasia. PMID- 8441190 TI - Adult multifocal extracardiac rhabdomyoma. AB - The occurrence of multifocal rhabdomyoma is exceedingly rare with less than half a dozen cases collected in the literature. We present a case of multifocal rhabdomyoma of the head and neck that involves extension of the tumor to the vallecula, the glossoepiglottic fold, and the aeriepiglottic fold. PMID- 8441191 TI - The Flexner Report and black academic medicine: an assignment of place. PMID- 8441192 TI - Providing adequate health care to all Americans: an open letter to president elect Clinton. PMID- 8441193 TI - Mycobacterium tuberculosis: resurgence of an old disease--current problems. PMID- 8441194 TI - Cardiovascular diseases and stroke in African Americans: a call for action. AB - Considerable disparities in cardiovascular and stroke mortality and morbidity rates exist between African Americans and other Americans. Increased prevalence and severity of hypertension, with earlier onset and often inadequate therapy, seem to be the major culprits responsible for the differences. There are ominous signs indicating that our recent dramatic progress in the control of cardiovascular disease and stroke is slowing, and in certain areas (stroke incidence and prevalence, hypertensive end-stage renal disease) progress is actually regressing. It is urgent that renewed research and medical interventions be undertaken to address this crisis. The American Heart Association and the National Medical Association have these and many other goals in common. Concerted action by all concerned organizations is essential. PMID- 8441195 TI - Looking ahead to next influenza season. PMID- 8441196 TI - Philip Morris recalls Marlboro cigarette lighter, considered 'enticing fire hazard for children'. PMID- 8441197 TI - What is age-associated memory impairment? PMID- 8441198 TI - Scientists chart course for brain map. PMID- 8441199 TI - From the Centers for Disease Control and Prevention. Minors' access to tobacco- Missouri and Texas. PMID- 8441200 TI - From the Centers for Disease Control and Prevention. Influenza activity--United States, 1992-1993. PMID- 8441201 TI - From the Centers for Disease Control and Prevention. Health status of Haitian migrants--U.S. Naval Base, Guantanamo Bay, Cuba, November 1991--April 1992. PMID- 8441202 TI - From the Centers for Disease Control and Prevention. Injuries to international petroleum drilling workers. PMID- 8441203 TI - From the Centers for Disease Control and Prevention. Business responds to AIDS program--1992-1993. PMID- 8441205 TI - From the Centers for Disease Control and Prevention. Adult blood lead epidemiology and surveillance. PMID- 8441204 TI - From the Centers for Disease Control and Prevention. Unintentional carbon monoxide poisoning following winter storm--Washington, January 1993. PMID- 8441206 TI - High-dose epinephrine in cardiopulmonary resuscitation. PMID- 8441207 TI - High-dose epinephrine in cardiopulmonary resuscitation. PMID- 8441208 TI - Substandard care, antidumping, and George Orwell. PMID- 8441209 TI - Substandard care, antidumping, and George Orwell. PMID- 8441210 TI - Underage drinking. PMID- 8441211 TI - Subspecialties and physician maldistribution. PMID- 8441212 TI - The California excise tax on cigarettes: the tobacco industry profits from this too. PMID- 8441213 TI - Exposure to environmental tobacco smoke in California. PMID- 8441214 TI - Sports participation, age at smoking initiation, and the risk of smoking among US high school students. AB - OBJECTIVE: To examine smoking patterns, smoking initiation, and the relationship of sports participation and age at smoking initiation to regular and heavy smoking among adolescents. DESIGN: Survey. PARTICIPANTS: A nationally representative sample of US high school students. OUTCOME MEASURES: Prevalences of smoking patterns, prevalence and incidence of smoking initiation, and prevalences and odds of regular and heavy smoking in relation to sports participation and age at smoking initiation. RESULTS: Seventy-two percent of students reported experimenting with, formerly, or ever smoking cigarettes, and 32% reported smoking in the past 30 days. Students who had participated in interscholastic sports were less likely to be regular and heavy smokers than were others who had not participated. Smoking initiation rates increased rapidly after age 10 years and peaked at age 13 to 14 years. Students who began smoking at age 12 years or younger were more likely to be regular and heavy smokers than were students who began smoking at older ages. CONCLUSIONS: These data suggest that smoking initiation at a young age can increase the risk of nicotine addiction during adolescence and that sports participation may influence smoking behavior. Interventions to prevent smoking should be available before age 12 years to help combat the smoking epidemic among youth. PMID- 8441215 TI - Health behavior and outcomes in sequential pregnancies of black and white adolescents. AB - OBJECTIVE: To examine the relationships among parity, preterm delivery, fetal growth retardation, and prenatal care utilization in first and second adolescent pregnancies. DESIGN: A longitudinal, retrospective study in which obstetric, behavioral, and sociodemographic data were used to examine birth outcomes of 737 low-income black (80%) and white (20%) teenagers delivering first and second singleton infants at 20 or more weeks' gestation. SETTING: Public health clinics in Jefferson County, Alabama, between January 1983 and February 1990. MAIN OUTCOME MEASURES: Mean birth weight, preterm delivery, fetal growth retardation, Apgar scores, and perinatal mortality. MAIN RESULTS: In their second pregnancies, adolescents presented 2.8 weeks later for care (P = .0001) and made fewer total clinic visits. Mean infant birth weight increased by 91 g (P = .0005). This increase was significantly associated with an increase in maternal prepregnancy body mass index. The rate of fetal growth retardation decreased (P = .0001) and the rate of preterm delivery increased (P < .02) in the second pregnancy. The rate of recurrence of fetal growth retardation was 13% and the rate of preterm delivery was 46%. CONCLUSIONS: Poorer utilization of prenatal care and high risk for recurrence of adverse outcomes are characteristic of adolescents' second pregnancies and should be considered in teenage pregnancy intervention programs. PMID- 8441217 TI - Current status and approaches to improving preventive services for adolescents. PMID- 8441216 TI - Confidentiality in health care. A survey of knowledge, perceptions, and attitudes among high school students. AB - OBJECTIVE: To assess adolescent knowledge, perceptions, and attitudes about health care confidentiality. DESIGN: Anonymous self-report survey with 64 items addressing confidentiality issues in health care. SETTING: Rural, suburban, and urban high schools in central Massachusetts. PARTICIPANTS: Students in ninth through 12th grades from three schools. RESULTS: A total of 1295 students (87%) completed the survey: 58% had health concerns that they wished to keep private from their parents, and 69% from friends and classmates; 25% reported that they would forgo health care in some situations if their parents might find out. There were differences in response by gender, race, and school. About one third were aware of a right to confidentiality for specific health issues. Of those with a regular source of care, 86% would go to their regular physician for a physical illness, while only 57% would go there for questions about pregnancy, the acquired immunodeficiency syndrome, or substance abuse that they wished to keep private. Sixty-eight percent had concerns about the privacy of a school health center. CONCLUSIONS: A majority of adolescents have concerns they wish to keep confidential and a striking percentage report they would not seek health services because of these concerns. Interventions to address confidentiality issues are thus crucial to effective adolescent health care. PMID- 8441218 TI - Promoting the healthy development of adolescents. PMID- 8441220 TI - Confidential health services for adolescents. Council on Scientific Affairs, American Medical Association. PMID- 8441221 TI - Making a difference in adolescent health. PMID- 8441219 TI - Should we be measuring blood cholesterol levels in young adults? AB - Should we measure blood cholesterol levels in all adults, or only in those at high risk of coronary heart disease (CHD)? Most men under the age of 35 years and women under the age of 45 years--roughly half the adult population--are at very low short-term risk of CHD. One consequence is that drug treatment to lower high blood cholesterol levels in the average young adult is an extremely expensive means of prolonging life; the estimated $1 million to $10 million per year of life is 100 to 1000 times the cost of other approaches. Individualized dietary treatment is somewhat cheaper but relatively ineffective. Another consequence of the low CHD risk in young adults is the greater likelihood that intervention may have harmful effects that outweight the benefits. Meta-analysis of primary prevention trials in middle-aged men reveal an increase in non-CHD deaths among those randomized to cholesterol interventions, an unexpected finding that is more substantial than the decrease in CHD deaths. This raises the possibility that one or more of the cholesterol interventions could have very serious adverse effects among young adults, whose risk of non-CHD death is normally 100 times their risk of CHD death. We conclude that the policy of screening and treating high blood cholesterol levels in young adults is neither cost-effective, nor does it satisfy ethical standards requiring strong evidence that preventive interventions do more good than harm. Fortunately, cholesterol screening in young adults is also not necessary: most CHD events associated with high blood cholesterol levels in this population will not occur for decades and can be prevented by treatment that is begun in middle age. Cholesterol screening and treatment in young adults should be limited to individuals with known coronary disease or other unusual factors that place them at high short-term risk of CHD death. PMID- 8441222 TI - Cholesterol testing in young adults. Prudent or profligate? PMID- 8441223 TI - Endopeptidase-24.11 and its inhibitors: potential therapeutic agents for edematous disorders and hypertension. PMID- 8441224 TI - PDGF-receptor localizes to mesangial, parietal epithelial, and interstitial cells in human and primate kidneys. AB - There is evidence that platelet derived growth factor (PDGF) is a mediator of proliferative changes in renal arteries and mesangium in human disease, in the mesangium in experimental mesangial proliferative glomerulonephritis, and in the interstitium in a rodent model of angiotensin II mediated hypertension. We utilized a monoclonal antibody to the beta-subunit of the PDGF-receptor to localize constitutive expression of this receptor in human and nonhuman primate tissues. Tissues were fixed in cold 2 or 4% paraformaldehyde, and immunohistochemical techniques both at the light microscopic level and immunoelectron microscopy were employed. In the glomerulus, there is widespread expression of this molecule by mesangial cells, and there is frequent expression on the apical and lateral surface of parietal epithelial cells. There is also widespread expression of this molecule by cortical and medullary peritubular interstitial cells, but not by glomerular or peritubular capillary endothelium or other renal parenchymal structures. The identification of receptors capable of binding PDGF B-chain at each of these sites: (1) provides a basis for PDGF mediated mesangial proliferation in human disease; (2) provides a basis for PDGF mediated interstitial cell migration and/or proliferation and/or activation at sites of tubulointerstitial injury; and (3) suggests that glomerular parietal epithelial cells may be responsive to stimulation by PDGF. PMID- 8441225 TI - Effect of protein kinase C activation and down-regulation on active calcium transport. AB - Active transcellular Ca2+ transport in primary cultures of the rabbit kidney collecting system has been shown to be responsive to PTH through activation of protein kinase A (PKA). The present study investigates an additional regulatory pathway activated by protein kinase C (PKC). Cells from rabbit kidney connecting tubules and cortical collecting ducts were isolated by immunodissection and subsequently cultured on permeable filters. Incubation of cultured cells with the PKC activator, 12-O-tetradecanoylphorbol 13-acetate (TPA, 10(-8) to 10(-6) M) had a dual effect on active transcellular Ca2+ transport. Short-term incubation increased membrane-associated PKC activity within 10 minutes and decreased active transcellular Ca2+ transport dose-dependently (IC50 = 3.4 +/- 0.4 nM), with a maximal inhibition of 74 +/- 3%. TPA (10(-7) M) concomitantly inhibited the amiloride-sensitive transepithelial potential difference (p.d.) and short-circuit current across the monolayers. After prolonged exposure to TPA, total cellular PKC activity was down-regulated, resulting in a maximal 65 +/- 5% reduction after one hour. Interestingly, this latter event was temporally separated from a gradual return of both Ca2+ absorption rate and transepithelial p.d. to control levels occurring over 96 and 48 hours, respectively, of further incubation with TPA. The inhibitor of protein kinase activity, staurosporine (10(-7) M), when present during incubation with submaximal concentration of TPA (10(-8) M) partly prevented the TPA-induced inhibition of Ca2+ absorption from 54 +/- 4 to 27 +/- 3%. This study demonstrates for the first time that, in addition to PKA, activation of PKC plays a regulatory role in transcellular Ca2+ reabsorption in the renal collecting system. PMID- 8441226 TI - Prostaglandin synthesis inhibition stimulates lithium reabsorption in Henle's loop in rats. AB - The effect of prostaglandin (PG) synthesis inhibition on tubular lithium (Li) handling in the rat was studied by micropuncture at the late proximal (LPT) and early distal (EDT) tubules. Animals received no treatment (N = 7), meclofenamate (MECLO; 5 mg/kg i.p. and 5 mg/kg i.v.; N = 7) or indomethacin (INDO, 1 mg/kg i.v.; N = 6). Whole kidney fractional Li excretion fell from 26.2 +/- 1.5% in control rats to 12.8 +/- 1.3% and 14.6 +/- 1.3% in MECLO and INDO treated rats. Fractional delivery of Li to the LPT was not affected by PG synthesis inhibition. All of the rise in tubular Li reabsorption took place between the LPT and EDT; at the EDT fractional Li delivery fell from 32.3 +/- 2.0% in the control group to 19.1 +/- 1.6% and 20.0 +/- 1.4% in the rats given MECLO or INDO. Water reabsorption between the LPT and EDT also increased. The tubular fluid/plasma Li concentration ratio ([T/P]Li) at the LPT was approximately 1.15 in all groups of rats. At the EDT, this ratio was approximately 1.06 in control rats, but only approximately 0.82 (P < 0.01) in rats subjected to PG synthesis inhibition. The finding that the [T/P]Li fell from values exceeding unity at the LPT to values below unity at the EDT during PG synthesis inhibition indicates that reabsorption of Li between these sites was stimulated to a greater extent than that of water. This dissociation strongly suggests that at least part of the increased Li reabsorption between the LPT and EDT took place in the water-impermeable thick ascending limb.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441227 TI - Extra-natriuretic effects of atrial peptide in humans. AB - To evaluate extra-natriuretic effects of atrial natriuretic peptide (ANP), plasma ANP (pANP) levels were assessed in seven healthy men on low-sodium diet (80 mEq NaCl/day), in basal conditions and during stepwise infusion of human ANP (2, 4, 8 and 16 ng/min/kg). To determine the individual physiological (PHY) pANP level, we measured pANP in the same subjects after a high-salt diet (400 mEq NaCl/day), that is, in a physiological stimulation of ANP. We then compared the effects of the PHY levels of ANP to the effects of pharmacological (PHA) pANP levels. Neither PHY nor PHA pANP levels modified creatinine clearance or blood pressure. The progressive rise in pANP levels was associated with increases in urinary excretion of Na+, K+ and urea. ANP alone respectively accounted for 41%, 30% and 92% of the increase in natriuresis, kaliuresis and urea excretion that occurred after changing salt intake from 80 to 400 mEq/day. Pharmacological ANP levels raised CH2O and reduced UOsm. Interestingly, PHA levels were associated with significant decrease in serum K+ (from 4.5 +/- .1 to 4.0 +/- .1 mEq/liter) and plasma urea (from 31.9 +/- 5 to 24.2 +/- 4 mg/dl). The mean cumulative urinary potassium and urea losses corresponded to the theoretical body losses of potassium and urea; moreover, the individual cumulative urinary losses of potassium and urea significantly correlated with the corresponding decrement in their plasma levels. In conclusion, ANP has both physiological and pharmacological significance in the control of potassium and urea metabolism by decreasing plasma levels of K+ and urea through effects on the renal excretory function. PMID- 8441228 TI - Visualization of serotonin effects on renal vessels of rats. AB - We studied the effects of serotonin (5-hydroxytryptamine, 5-HT) on glomerular blood flow (GBF) and on renal vessel diameters in the hydronephrotic kidney and in vascular casts of normal kidneys of rats. 5-HT (60 min after local application of 10(-8) mol.liter-1) constricted the arcuate arteries (-10 +/- 2% to -14 +/- 2%, mean +/- SEM), dilated the interlobular arteries (+13 +/- 2%) and afferent arterioles (+17 +/- 3%), and decreased GBF (-44 +/- 5%). In contrast to normal autoregulation, reduction of renal perfusion pressure after local application of 5-HT from 118 +/- 3 mm Hg by 10 and 20 mm Hg reduced GBF by 12 +/- 2% and 23 +/- 3%, respectively. The 5-HT2 antagonist, ritanserin (60 min after local application of 10(-6) mol.liter-1), dilated all preglomerular vessels and increased GBF. In the presence of ritanserin, 5-HT lost nearly all vascular effects. During infusion of 5-HT (5 micrograms.min-1 i.v. for 20 min) vascular reactions were similar to those under local application. After cyclooxygenase inhibition with indomethacin, infusion of 5-HT failed to constrict the arcuate arteries whereas vasodilation of the small preglomerular vessels remained unaffected. Analyzing vascular casts of normal kidneys we observed considerable vascular spasms and an average vasoconstriction of the interlobar arteries of 19 +/- 9% after i.v. infusion of 5-HT. We believe that 5-HT decreases GBF by 5-HT2 receptor-mediated constriction of the large renal vessels which are modulated by the prostaglandin system, whereas 5-HT dilates the small preglomerular vessels, most likely via 5-HT1-like receptors. Furthermore, our data indicate that 5-HT impairs the myogenic component of renal autoregulation in the low pressure range. PMID- 8441229 TI - Renal basement membranes by ultrahigh resolution scanning electron microscopy. AB - Three-dimensional ultrastructures of basement membranes of the rat kidney were investigated with an ultrahigh resolution scanning electron microscope (HSEM) equipped with a resolving power of 0.5 nm. All cellular components were extracted from renal cortical tissues by sequential-detergent treatment. Four types of acellular basement membranes were observed after tannin-osmium conductive staining: the glomerular basement membrane (GBM) associated with the mesangial matrix, the tubular basement membrane (TBM), the Bowman's capsule basement membrane (BCBM), and the peritubular capillary basement membrane (PTCBM). We could demonstrate the polygonal meshwork structures composed of strands in the respective basement membranes. The strands averaged 6 to 7 nm wide, whereas the pore sizes within the meshworks were variable and differed according to the basement membrane type. Moreover, we confirmed the presence of the heterogeneity of the GBM suggested by several approaches. Present data support the proposition that a polygonal meshwork structure may represent the basic structure of basement membrane. Some of the observed architectural dissimilarities in basement membrane types may reflect their different functional properties, which in turn may reflect the heterogeneous distribution of major basement membrane components as demonstrated by immunohistochemical and biochemical studies. PMID- 8441230 TI - Renal endothelin gene expression is increased in remnant kidney and correlates with disease progression. AB - We previously demonstrated that urinary endothelin excretion is increased in rats with extensive renal mass reduction, a model of progressive renal disease. Here we explored whether the increased urinary endothelin in this model were due to induction of renal pre-pro-endothelin-1 gene and whether changes in endothelin synthetic pathway correlated with the development of glomerulosclerosis. Four groups of rats with renal mass reduction and four groups of sham-operated control rats were studied 7, 30, 60 and 120 days after the surgical procedure. Urinary protein excretion in renal mass ablation animals did not differ from controls at seven days, but was already significantly elevated (P < 0.01) 30 days after surgery. Then proteinuria progressively increased in rats with remnant kidney at values above 400 mg/day at day 120. Serum creatinine concentration also progressively increased with time in renal mass ablation rats, unlike sham operated animals, and values were significantly different (P < 0.01) at each of the points considered. Rats with renal mass reduction, unlike sham-operated animals, developed focal glomerulosclerosis that affected 8% of glomeruli at day 30, and 24% of glomeruli at day 120. Seven days after renal mass reduction renal pre-pro-endothelin-1 (pre-pro ET) mRNA was comparable to that of sham-operated rats, while a 2.5-, 5- and fourfold increase in 2.3 Kb pre-proET-1 transcript was observed at 30, 60 and 120 days, respectively. Urinary excretion of endothelin was significantly elevated (P < 0.01) in rats with renal mass reduction with respect to sham-operated rats, starting from 30 days after surgery and increased further thereafter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441231 TI - Fish oil has protective and therapeutic effects on proteinuria in passive Heymann nephritis. AB - Passive Heymann nephritis (PHN) is a rat model of membranous nephropathy induced by injecting anti-Fx1A. The onset of proteinuria in PHN is caused by complement mediated injury to glomerular epithelial cells (GEC) accompanied by enhanced glomerular eicosanoid production. In addition, sublethal injury by complement of rat GECs in culture leads to phospholipase activation, phospholipid hydrolysis and release of arachidonic acid and dienoic prostanoids. Based on these findings, we undertook to determine if substituting arachidonic acid (omega-6) in GEC membrane phospholipids with omega-3 fatty acids derived from fish oil would alter the development and course of proteinuria in PHN. We found that rats fed a diet containing 10% fish oil for four weeks prior to antibody injection developed 50 to 60% less proteinuria between two and six weeks after anti-Fx1A than rats fed an equivalent diet containing 10% safflower oil, and had substantial enrichment of glomerular phospholipids with omega-3 fatty acids and displacement of arachidonic acid. This outcome was associated with a 50% reduction in release of glomerular thromboxane B2 (stable metabolite of thromboxane A2) in the fish oil group. More importantly, when PHN rats with well established proteinuria while on regular chow were randomized to three dietary groups, those fed fish oil had a 25 to 50% decline in proteinuria as compared to those fed lard or safflower oil. This difference was evident within two weeks of randomization and persisted until the end of the study after eight weeks. In neither study could the differences in urine protein excretion be accounted for by protein or calorie deprivation, or by differences in blood pressure, renal function, immune response to sheep IgG, or glomerular deposition of IgG or complement. Thus, our results indicate that dietary fish oil has protective and therapeutic effects with regard to proteinuria in PHN. These benefits may relate to alterations in membrane phospholipid composition in favor of omega-3 fatty acids and release of less reactive trienoic eicosanoids. PMID- 8441232 TI - Heparin suppresses mesangial cell proliferation and matrix expansion in experimental mesangioproliferative glomerulonephritis. AB - Proliferation and extracellular matrix (ECM) overproduction by glomerular mesangial cells characterizes many types of glomerulonephritis and often precedes the development of glomerulosclerosis. Heparin is a potent inhibitor of mesangial cell growth in vitro. We examined whether standard heparin can inhibit mesangial cell proliferation in vivo in the mesangioproliferative anti-Thy 1.1 nephritis. Untreated control rats were compared to rats infused with heparin either early (day -2 to 1) or late (day 2 to 5) after induction of anti-Thy 1.1 nephritis. The results show that heparin treatment significantly reduced mesangial cell proliferation regardless of when it was initiated. Heparin (either early or late treatment) also reduced mesangial basic fibroblast growth factor (bFGF) expression and platelet-derived growth factor (PDGF) receptor up-regulation as reflected by immunostaining, whereas PDGF B-chain expression was reduced only by late heparin treatment. Furthermore, heparin treatment markedly inhibited the mesangial matrix expansion for a variety of ECM proteins, including laminin, type I and IV collagen, fibronectin and entactin. Heparin did not affect the initial mesangiolysis, glomerular macrophage influx, deposition of anti-Thy 1.1 IgG or fibrinogen, or the glomerular platelet influx. These results suggest that heparin, via its antiproliferative rather than anticoagulant effect, can inhibit mesangial cell proliferation, overexpression of polypeptide growth factors, and ECM protein overproduction in vivo. The beneficial effect of heparin can be demonstrated even if treatment is initiated after the development of nephritis. By virtue of these properties, heparin may be an effective agent in the treatment of human mesangioproliferative disease and in the prevention of glomerulosclerosis. PMID- 8441233 TI - Structural-functional relationships in type I mesangiocapillary glomerulonephritis. AB - We quantitated glomerular and cortical interstitial structures in nine type I mesangiocapillary glomerulonephritis (MCGN) patients aged 6 to 20 years whose creatinine clearance (CCr) was 10 to 129 ml/min/1.73 m,2 as compared to age matched normal controls. Mean glomerular volume and mesangial volume fraction [Vv(mes/glom)] were increased and the percentage of the capillary endothelial circumference which was defined as filtration surface was decreased in type I MCGN patients. Vv(mes/glom) was inversely related to filtration surface area per glomerulus (r = -0.73, P < 0.05) and directly to volume density of cortical interstitium [Vv(int/cortex)] (r = +0.90; P < 0.01). Vv(mes/glom) (r = -0.87; P < 0.01), filtration surface area per glomerulus (r = +0.83; P < 0.01) and Vv(int/cortex) (r = -0.86; P < 0.01) were correlated with CCr. Thus, in type I MCGN, measures both of glomerular and of cortical interstitial structure are highly correlated with glomerular function. PMID- 8441234 TI - Effects of insulin-like growth factor I on renal function in normal men. AB - Acute and chronic studies in rats have shown that administration of human recombinant insulin-like growth factor I (rhIGF-I) lowers renal vascular resistance and increases RPF, GFR and proximal tubular phosphate absorption. In the present study we examined the effects of subcutaneous injections of rhIGF-I on glomerular and tubular function in eight normal men. Individuals were studied for 5.5 consecutive days in a clinical research center while they ate a constant diet. Four subjects were studied in a non-volume expanded state (Group 1) and four individuals were evaluated during a saline load. From the second to the fourth day, subjects received subcutaneous injections of rhIGF-I, 60 micrograms/kg, at 0800, 1400 and 2000 hours. After commencing the rhIGF-I injections, serum IGF-I levels rose quickly and remained at about three to four times that of baseline throughout the period of rhIGF-I injections. In both the normal and the saline loaded subjects, renal vascular resistance decreased and RPF and GFR (PAH and inulin clearances) rose quickly and were clearly altered within six hours after starting the rhIGF-I injections. RPF had increased by 32 +/- 3% and 33 +/- 2% (grand mean +/- SEM) in the normal and the saline loaded subjects, and GFR rose by 22 +/- 3% and 36 +/- 4% in the two groups. In both groups the absolute and the fractional excretion of phosphate decreased markedly during rhIGF-I treatment, but the absolute and fractional excretion of calcium did not change. The urinary fractional and absolute excretion of albumin and IgG also increased, although slightly, with rhIGF-I injections. There was no consistent effect of IGF-I on tubular sodium handling. These findings demonstrate that in normal men subcutaneous injections of rhIGF-I greatly increase RPF, GFR, and tubular phosphorus reabsorption and enhances microproteinuria. PMID- 8441235 TI - Effects of kidney or kidney-pancreas transplantation on plasma pentosidine. AB - Tissue and plasma concentrations of pentose-derived glycation end-products ("pentosidine") are elevated in diabetic patients with normal renal function and in both diabetic and nondiabetic patients with end-stage renal disease. To determine the effects of correcting hyperglycemia and/or renal failure on the accumulation of pentosidine, we used reverse phase and ion exchange high performance liquid chromatography to measure this advanced glycation end-product in plasma proteins of diabetic and nondiabetic transplant recipients at various time intervals after kidney-pancreas or kidney transplantation. Changes in plasma pentosidine levels after transplantation were compared to changes in simultaneously obtained glycohemoglobin levels. Both kidney and kidney-pancreas transplantation were accompanied by a dramatic, but incomplete, reduction of plasma pentosidine concentrations within three months of transplantation. Kidney pancreas transplantation resulted in normal glycohemoglobin levels within three months but offered no advantage over kidney transplantation alone in the partial correction of plasma pentosidine levels. There was no correlation between posttransplant plasma pentosidine and glycohemoglobin levels in either diabetic or nondiabetic transplant recipients. We conclude that renal failure is the major factor accounting for the accumulation of pentosidine in both diabetic and nondiabetic patients with end-stage renal disease. Restoration of euglycemia after kidney-pancreas transplantation provides no additional benefit in reducing plasma pentosidine levels to that achieved by correction of renal failure after kidney transplantation alone. PMID- 8441236 TI - Survival analysis of dialysis patients in Okinawa, Japan (1971-1990). AB - We analyzed longitudinal data obtained from the initiation of chronic dialysis in Okinawa, Japan. A total of 1,982 patients (824 females and 1,158 males) were registered in the Okinawa Dialysis Study (OKIDS) up to the end of 1990. The number of patients dying, undergoing renal transplantation, or being transferred was 605 (30.5%), 75 (3.8%), and 23 (1.2%), respectively. The mean acceptance rate per million population increased from 19.7 in 1971 to 1975 to 157.4 in 1986 to 1990. The percentage of diabetic patients and the annual gross mortality rate were, respectively 0% and 0.52 (1971 to 1975), 7.3% and 0.12 (1976 to 1980), 14.4% and 0.06 (1981 to 1985), and 24.6% and 0.07 (1986 to 1990). Cox proportional hazard analysis was used to determine the relative risk (RR) for sex, primary renal disease, age at entry, and the year of starting dialysis. The RR for males was 1.09 (1.00 for females) and the 95% confidence interval (CI) was 0.93 to 1.28. The RR for diabetics was 1.88 (95% CI; 1.55 to 2.28) when that for nondiabetics was set at 1.00. The RR (95% CI) for starting dialysis in 1976 to 1980, 1981 to 1985, and 1986 to 1990 was 0.65 (0.59 to 0.72), 0.43 (0.35 to 0.52), and 0.28 (0.20 to 0.38), respectively, when the RR in 1971 to 1975 was taken as 1.00. During the last two decades, the survival of chronic dialysis patients in Okinawa has continued to improve despite the large increase in acceptance rate, the older age of the new patients, and the increase in diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441237 TI - Lipoprotein heterogeneity in end-stage renal disease. AB - Fifteen patients on chronic maintenance hemodialysis without any additional known cause for dyslipidemia were arbitrarily divided into two groups based on fasting plasma triglyceride levels. The hypertriglyceridemic patients (plasma triglyceride levels above 170 mg/dl, N = 7) also had decreased high density lipoprotein (HDL) cholesterol levels and decreased post-heparin plasma lipoprotein lipase activity compared to the normotriglyceridemic patients (N = 8). All lipoprotein fractions collected by density gradient ultracentrifugation were triglyceride-enriched in the hypertriglyceridemic patients. Both groups of patients had elevated intermediate density lipoprotein levels, heterogeneity in the distribution of low density lipoproteins (LDL) and apoprotein-specific HDL subpopulations, and abnormalities in the size and composition of both LDL and HDL. The described alterations tended to be more marked in hypertriglyceridemic patients and are not detected by the usual laboratory evaluation of lipoproteins. These lipoprotein abnormalities have been shown to be atherogenic in patients without renal disease and are likely to contribute to the high prevalence of premature atherosclerosis in end-stage renal disease. PMID- 8441238 TI - Urinary excretion of platelet activating factor in patients with immune-mediated glomerulonephritis. AB - We have investigated whether human immune-mediated glomerulonephritis is associated with changes in platelet activating factor (PAF) biosynthesis. Urinary PAF, taken as a marker of its renal synthesis, was significantly higher in patients with membranous nephropathy (N = 9) than in healthy controls (N = 8). This was not due to a lower degradation of PAF since urinary acetylhydrolase activity was comparable in patients and controls. A significant positive correlation between urinary excretion of PAF and proteinuria was observed. PAF generation was comparable in polymorphonuclear cells isolated from patients with membranous nephropathy and controls. PAF levels in blood from patients with membranous nephropathy were significantly lower than in controls, suggesting that the excessive generation of PAF is confined to the kidney. The results document that signs of renal disease activity in human membranous nephropathy are associated with an excessive renal synthesis of PAF. PMID- 8441239 TI - Localization of apolipoprotein(a) and B-100 in various renal diseases. AB - Recently it has become clear that abnormalities of lipid metabolism play a large role in the progression of renal diseases. To investigate the relationship between lipids and kidney tissue, we employed an immunofluorescent technique to determine the localization pattern of apolipoprotein(a) [apo(a)], apoB-100, and low-density lipoprotein receptor in the glomeruli, and analyzed the relationship between their presence and the clinical and histological findings of a total 92 patients with glomerular diseases. Immunostaining showed co-localization of apo(a) and apoB-100 in glomeruli. The patients were divided into three groups, as follows: both apo(a) and apoB-100 positive (Group 1; 38 cases), apo(a) positive only (Group 2; 19 cases) and apo(a) negative (Group 3; 35 cases). Group 1 had more severe proteinuria, higher levels of lipoprotein(a) [Lp(a)], and lower total protein levels than Group 3. Group 1 had a higher prevalence of glomerulosclerosis and interstitial changes than Group 3. Group 2 had more severe proteinuria and a higher prevalence of glomerulosclerosis than Group 3. Although apo(a) and apoB-100 are almost absent in normal controls, these apoproteins [and presumably lipoproteins Lp(a)] are present in the glomeruli of patients with glomerular diseases. The data support the view that these apoproteins play a significant role in progressive renal diseases. PMID- 8441240 TI - The spectrum of bone disease in end-stage renal failure--an evolving disorder. AB - We have assessed the bone histology in 259 chronic dialysis patients, all of whom were in the same dialysis program. All patients had bone biopsies with quantitative histomorphometry, intact parathyroid hormone (PTH) measurements, basal and deferoxamine stimulated serum aluminum levels. Results demonstrate the increased incidence of the recently described aplastic bone lesion, particularly in patients treated with peritoneal dialysis (PD). Aluminum-related bone disease is much less common than previously described, perhaps in relation to the declining use of aluminum as a phosphate binder. A different pattern of bone lesions is seen in PD as compared with hemodialysis (HD), with low turnover disorders comprising 66% of the lesions seen in PD and high turnover lesions accounting for 62% of the bone histologic findings in HD. The difference in these patterns may relate to alterations in PTH levels, as mean PTH levels in HD patients were 2-1/2 times the levels found in PD patients (P < 0.0005), while older age, higher prevalence of diabetes and a shorter duration of dialysis may also have contributed to the findings in the PD patients. We suggest that PD, perhaps by maintaining calcium at higher levels, may more effectively suppress the parathyroid gland. PMID- 8441241 TI - Effects of dietary protein restriction on hemodynamics in chronic renal failure. AB - To elucidate the effect of protein and phosphorus restriction on hemodynamics in chronic renal failure, 14 patients were placed on a low-protein very-low phosphorus diet (LPVLPD) and observed for metabolic and hemodynamic changes. For three weeks after initiation of the LPVLPD, the patients displayed a positive sodium balance in spite of dietary sodium restriction. During the fourth week, sodium balance decreased and approached zero. Sodium retention was accompanied by a significant decrease in plasma renin activity (P < 0.05) and mean blood pressure (P < 0.01), an increase in body weight (P < 0.05), a slight temporary decrease in hemoglobin (P < 0.05), hematocrit (P < 0.05) and total protein (P < 0.005), a negative nitrogen balance, and an increase in left ventricular ejection fraction (P < 0.01) and peak filling rate (P < 0.05). Serum creatinine concentration and endogenous creatinine clearance did not change during the experiment. These data indicate a role of dietary protein and phosphorus restriction in cardiac and fluid homeostasis in the pathophysiology of chronic renal failure. PMID- 8441242 TI - Organic osmolytes in human and other mammalian kidneys. AB - Osmotically-active organic solutes, or osmolytes, have been found in high concentration in the renal inner medulla of a wide variety of mammalian species, but their existence in human kidneys has not yet been shown. The aim of this study was to demonstrate the presence of osmolytes in the human kidney. Human tissues were obtained from kidneys removed surgically for diseases which involved only one pole of the kidney; in most cases this was a tumor. Animal kidneys analyzed were from dogs, pigs and rabbits. Inner medulla and cortex tissue samples were analyzed and found to contain the organic osmolytes glycine betaine, myo-inositol, sorbitol and glycerophosphorylcholine. The levels were much higher in the medulla than in the cortex. Further dissection of the human kidneys showed that sorbitol, glycerophosphorylcholine and glycine betaine were maximally concentrated at the papillary tip, while myo-inositol was found in highest concentration at the papillary base. Osmolytes were in low concentrations or undetectable in rabbit skeletal muscle, ureter and bladder. The organic osmolytes detected are likely to be physiologically important in humans. Studies in other mammals can be used as models for the investigation of the osmolyte system in human kidney function. PMID- 8441243 TI - Distribution of GBM heparan sulfate proteoglycan core protein and side chains in human glomerular diseases. AB - Using monoclonal antibodies (mAbs) recognizing either the core protein or the heparan sulfate (HS) side chain of human GBM heparan sulfate proteoglycan (HSPG), we investigated their glomerular distribution on cryostat sections of human kidney tissues. The study involved 95 biopsies comprising twelve different glomerulopathies. Four normal kidney specimens served as controls. A homogenous to linear staining of the GBM was observed in the normal kidney with anti-HSPG core mAb (JM-72) and anti-HS mAb (JM-403). In human glomerulopathies the major alteration was a segmental or total absence of GBM staining with anti-HS mAb JM 403, which is most pronounced in lupus nephritis, membranous glomerulonephritis (GN), minimal change disease and diabetic nephropathy, whereas the HSPG-core staining by mAb JM-72 was unaltered. In addition we found HSPG-core protein in the mesangial matrix when this was increased in membranoproliferative GN Type I, Schonlein-Henoch GN, IgA nephropathy, lupus nephritis, diabetic nephropathy and in focal glomerulosclerosis. Also staining with the anti-HS mAb JM-403 became positive within the mesangium, although to a lesser extent. Furthermore, amyloid deposits in AL and AA amyloidosis clearly stained with anti-HSPG-core mAb JM-72, and to a lesser degree with anti-HS mAb JM-403. Finally, in membranous GN (stage II and III), the GBM staining with anti-HSPG-core mAb JM-72 became irregular or granular, probably related to the formation of spikes. In conclusion, major alterations were observed in the glomerular distribution of HS and HSPG-core in various human glomerulopathies. The mAbs can be useful to further delineate the significance of HSPG and HS for glomerular diseases. PMID- 8441244 TI - Permeable type I collagen membrane promotes glomerular epithelial cell growth in culture. PMID- 8441245 TI - Suppression of experimental crescentic glomerulonephritis by the interleukin-1 receptor antagonist. AB - The role of interleukin-1 (IL-1) in the pathogenesis of experimental crescentic glomerulonephritis was investigated. Administration of the interleukin-1 receptor antagonist (IL-1ra) was used to block the action of IL-1 during disease development. Two groups of six rats were primed with rabbit IgG, followed five days later by injection of rabbit anti-GBM serum (day 0). Animals were treated with a constant infusion of recombinant human IL-1ra (plasma level approximately 100 to 200 ng/ml) or saline (untreated) from day -1 until being killed on day 14. Untreated animals exhibited severe proteinuria and development renal dysfunction shown by increased serum urea and serum creatinine and reduced creatinine clearance. In contrast, IL-1ra treated animals had significantly reduced proteinuria (IL-1ra vs. untreated, P < 0.05) and maintained normal renal function (IL-1ra vs. untreated, P < 0.05). Histologically, IL-1ra treatment markedly reduced glomerular hypercellularity, glomerular necrosis and crescent formation and almost completely abrogated tubular atrophy and fibrosis. IL-1ra treatment suppressed glomerular macrophage accumulation by 57% (P < 0.01), while macrophage accumulation in the interstitium was completely abrogated and immune activation of the interstitial T cell infiltrate was prevented. This study demonstrates that IL-1 plays a key role in the pathogenesis of anti-GBM glomerulonephritis, and blocking its effects may provide a novel therapeutic approach to the treatment of human progressive glomerulonephritis. PMID- 8441246 TI - COL4A5 splice site mutation and alpha 5(IV) collagen mRNA in Alport syndrome. AB - Mutations affecting the COL4A5 gene encoding the alpha 5 chain of type IV collagen, are involved in the pathogenesis of X-linked Alport syndrome. We used denaturing gradient gel electrophoresis (DGGE) to screen PCR amplified exons of COL4A5 for point mutations in a set of 18 Alport patients previously characterized by Southern blotting. One sequence variant was identified in the exon 38 region of a male Alport patient. Sequence analysis revealed a G to C transversion in the 5' intron splice donor site downstream from exon 38 (GT to CT). To determine the effect of the mutation on mRNA splicing, alpha 5(IV) cDNA was generated from total RNA of peripheral blood lymphocytes. Subsequent cDNA PCR yielded a product 81 base pairs shorter in the affected Alport patient, compared to normal controls. The absence of exon 38 from the alpha 5(IV) cDNA was confirmed by sequence analysis. The results demonstrated that the mutation leads to skipping of exon 38 in the processing of alpha 5(IV) pre-mRNA. The shortened transcript lacked 27 codons encoding a Gly-X-Y-repeat sequence with a preserved reading frame, enabling the translation of codons further downstream. Clinically, the patient presented with juvenile onset Alport syndrome, end-stage renal failure, and deafness. He had no ocular lesions. Typical ultrastructural changes of the glomerular basement membrane (GBM) were shown on electron microscopy. The patient developed anti-GBM antibodies after renal transplantation, however, renal function deteriorated only moderately. PMID- 8441247 TI - Renovascular disease in children. PMID- 8441248 TI - From serum sickness to cytokines: advances in understanding the molecular pathogenesis of kidney disease. PMID- 8441249 TI - Mucosal immunity, HIV transmission, and AIDS. PMID- 8441250 TI - Transforming growth factor-beta protein and mRNA in glomeruli in normal and diseased human kidneys. AB - BACKGROUND: Evidence indicates a key role for transforming growth factor-beta (TGF-beta) in the accumulation of pathologic extracellular matrix in experimental glomerular injury. The aim of this study was to elucidate the expression of TGF beta and its role in human glomerulonephritis. EXPERIMENTAL DESIGN: Expression of TGF-beta 1 in normal and diseased human kidneys was examined by immunohistochemical staining with two antibodies (Ab1 and Ab2), and by in situ hybridization with an oligonucleotide probe. RESULTS: Staining with Ab1, which mainly recognizes mature TGF-beta 1 and the latency-associated peptide (LAP) of natural TGF-beta 1, was linearly positive along the glomerular basement membrane (GBM) and weakly so in the mesangium of normal tissues and those of various glomerular diseases which were pretreated with acid-urea to unmask a hidden epitope. Ab2, which reacts mainly with TGF-beta-LAP, bound to the mesangium and sclerotic areas of the tissues untreated with acid-urea. Immunoelectron microscopy showed that Ab1 was localized to the GBM and the mesangial matrix, and that Ab2 was distributed in subepithelial, or mesangial/paramesangial electron dense deposits. The presence of mature TGF-beta 1 and TGF-beta-LAP in normal kidneys was confirmed by immunoblotting using guanidine-extracted fractions of glomeruli and GBM isolated from normal human kidneys. Mesangial staining of TGF beta 1 with Ab2 was significantly correlated with the mesangial matrix increase in mesangial proliferative types of nephritis. In situ hybridization revealed TGF beta 1 mRNA expression in glomerular cells. Cells with positive mRNA signals were evident in glomeruli that were increased in both mesangial cells and TGF-beta 1 protein expression. The glomerular cells with positive signals were numerous, compared with the number of infiltrating monocyte-macrophages identified with a monoclonal antibody. CONCLUSIONS: These results indicate that mature TGF-beta and TGF-beta-LAP are localized in association with the matrix components of GBM or mesangium, and with immune deposits in human glomeruli. Glomerular expression of TGF-beta is enhanced in human glomerular diseases, and may contribute to the mesangial matrix increase. PMID- 8441252 TI - Peripherin immunoreactive structures in amyotrophic lateral sclerosis. AB - BACKGROUND: Increased levels of the neuron-specific intermediate filament, peripherin, have been recently detected in regenerating motor neurons of rat spinal cord after nerve transection. No data are yet available on peripherin expression in normal and diseased human spinal cord. EXPERIMENTAL DESIGN: We have investigated the presence of peripherin immunoreactive structures in routinely processed spinal cord of human patients with amyotrophic lateral sclerosis and control cases by immunohistochemistry and immunoelectron microscopy. Adjacent sections were stained with antibodies to neurofilaments (NF) and ubiquitin. RESULTS: In control cases, immunoreactivity for peripherin was found in neurons of dorsal root ganglia, in the posterior columns, in dorsal and ventral roots, and in scattered age-related axonal swellings. The cytoplasms of motor neurons were unstained. In amyotrophic lateral sclerosis cases most spheroids were immunoreactive for NF and to a lesser extent for peripherin. A few spheroids were strongly reactive for peripherin and were only weakly stained by antibodies to NF in adjacent sections. Both antibodies to NF and peripherin failed to demonstrate structures corresponding to the intraneuronal filamentous inclusions labeled by ubiquitin. CONCLUSIONS: The accumulation of peripherin and NF in spheroids is likely related to the reduced anterograde transport. Alternatively, the spheroids showing a higher degree of peripherin immunoreactivity might represent regenerating axonal terminals. PMID- 8441251 TI - Hypertensive nephrosclerosis in the Dahl/Rapp rat. Initial sites of injury and effect of dietary L-arginine supplementation. AB - BACKGROUND: The Dahl/Rapp strains of salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) rat were developed to examine pathogenetic mechanisms that produce hypertension in response to an increase in dietary salt. We have shown that providing SS/Jr rats with L-arginine, the metabolic precursor of nitric oxide, acutely prevented salt-sensitive hypertension, suggesting that SS/Jr rats developed hypertension because of inadequate nitric oxide production while on a high-salt diet. EXPERIMENTAL DESIGN: Male 23-day SS/Jr and SR/Jr rats were placed on chow that contained 8% sodium chloride. One group of SS/Jr rats also received L-arginine, 1.25 g/liter, in their drinking water. These three groups were examined at weekly intervals for 4 weeks. RESULTS: SS/Jr rats rapidly developed hypertension when placed on the high-salt chow. After 2 weeks on this diet, inulin clearance dramatically decreased, and albumin excretion rate increased. By the fourth week of study, SS/Jr rats on the high-salt diet had died or were dying. Coincident with the progressive decline in inulin clearance, renal morphologic analysis confirmed development of myointimal thickening, fibrinoid necrosis, and glomerulosclerosis. In contrast, over the 4 weeks of study, SS/Jr rats supplemented with oral L-arginine did not develop hypertension and any of the associated renal complications seen in age-matched SS/Jr rats on the high salt diet. L-Arginine also corrected hypertension in SS/Jr rats exposed to the high-salt chow for 2 weeks before the inception of L-arginine. L-Arginine administration after 3 weeks on this chow, however, failed to reverse hypertension and the depressed inulin clearance and morphologic renal damage. CONCLUSIONS: Along with previous work (Chen PY, Sanders PW, J Clin Invest 88:1559 67), these studies were consistent with the hypothesis that hypertension and hypertensive nephrosclerosis developed in SS/Jr rats because, while on a high salt diet, substrate (L-arginine) became a rate-limiting factor in the synthesis of nitric oxide. PMID- 8441253 TI - The pallid mouse. A model of genetic alpha 1-antitrypsin deficiency. AB - BACKGROUND: The current hypothesis of pulmonary emphysema is based on an alteration of the protease-antiprotease balance within the lower respiratory tract. This hypothesis derives largely from studies in emphysema patients with genetic deficiency in serum alpha 1-antitrypsin. In animals, naturally occurring deficiency in serum elastase inhibitory capacity associated with early development of emphysema has been reported in the tight-skin mouse. We describe here a mouse model of genetic deficiency of alpha 1-antitrypsin in which emphysema occurs late in life. EXPERIMENTAL DESIGN: A genetic deficiency in serum alpha 1-antitrypsin was investigated in pallid mice, a strain with spontaneous occurring emphysema. Additionally, the possible pathogenetic role of an elastase anti-elastase imbalance in pallid mice was investigated using molecular biologic, biochemical, histologic, ultrastructural, and immunoelectron microscopic methods. RESULTS: Pallid mice have markedly low levels of serum alpha 1-antitrypsin associated with a severe deficiency in serum elastase inhibitory capacity. However, they have normal alpha 1-antitrypsin mRNA levels in the liver. At ultrastructural examination, disruption of alveolar septa is first seen at 8 months of age. At histologic examination, some patchy areas of air-space enlargement with destruction of alveolar septa are seen from 12 months of age onward. These histologic changes are paralleled by a decrease in lung elastin content. The development of the pulmonary lesions is preceded by an alveolar elastolytic burden detected by an immunogold technique. CONCLUSIONS: All these data suggest that the lung changes in pallid mice are the result of an elastolytic process due to a severe inborn deficiency of serum alpha 1 antitrypsin. This animal model reproduces important features of the human condition and may provide new insights into the pathogenesis of emphysema. PMID- 8441254 TI - Prediction of operative mortality based on impairment of host defense systems in patients with esophageal cancer. AB - To determine whether operative risk based on impaired defense systems can be predicted, we examined 21 markers in 32 patients with esophageal cancer seen between 1983 and 1985 and related them to postoperative deaths. A discriminant analysis proved useful in determining whether the patient would be at risk of operative mortality, based on impaired defense systems. This model, the host defense index (HDI), was then used clinically to evaluate findings in 64 patients seen between 1986 and 1991. During this period, a change in policy for performing transthoracic esophagectomy on and perioperative care for patients with impaired defense systems was associated with a decrease in operative mortality. Thus, the HDI is beneficial to predict the risk of operative mortality based on impaired defense systems in patients with esophageal cancer. PMID- 8441255 TI - Cervical exploration for primary hyperparathyroidism. AB - The classical presentation of primary hyperparathyroidism, "moans, bones, groans," is no longer commonly seen since the diagnosis of hypercalcemia is now made much earlier with the routine use of the SMA 12. In the past 8 1/2 years, 85 patients underwent cervical exploration in our institution for primary hyperparathyroidism. There were 34 male and 51 female patients, ranging in age from 18-84 years. The specific symptoms included hypertension in 40 patients, generalized weakness in 25, renal stones in 14, psychiatric problems in 2, and bone changes on X-ray in 4. Forty-one patients were totally asymptomatic. The diagnosis was made mainly on the basis of history, serum calcium and phosphorous levels, parathormone assay, and 24-hour urinary calcium studies. Preoperative localization studies were performed in 38 patients. Thallium technetium subtraction scans, when positive, were very helpful. The surgical approach involved stepwise exploration of both sides of the neck with identification of all four parathyroid glands. In patients with uniglandular pathology (87%), the adenoma was removed with biopsy of at least one normal gland. In multiglandular disease, the abnormal glands were removed. Frozen section was routinely performed to confirm the presence of parathyroid tissue and no attempt was made to pathologically distinguish adenoma from hyperplasia. Two patients had parathyroid carcinoma. In three patients, serum calcium levels did not fall, resulting in an operative success rate of 96%. One patient treated by subtotal parathyroidectomy developed permanent hypoparathyroidism and one other patient developed temporary hypocalcemia. Only a single patient developed vocal cord palsy. Early exploration in patients with primary hyperparathyroidism is indicated. The basic diagnostic workup is sufficient for initial exploration. It is important to distinguish uniglandular from multiglandular pathology after careful bilateral exploration and identification of all four parathyroid glands. PMID- 8441256 TI - Composite reconstruction of the esophagus. AB - Composite reconstruction of the esophagus using both the mobilized stomach and free jejunal graft is described. Tension at the anastomotic site can be minimized with interposition of a jejunal autograft between the pharyngeal stump and the mobilized stomach, even when the mobilized stomach is not long enough. Furthermore, problems derived from differing calibers of the pharyngeal stump and the mobilized stomach can be resolved by creating an end-to-side pharyngojejunal anastomosis. Our method is proposed as one procedure for reconstruction of the esophagus when the pull-up organ is too short. PMID- 8441257 TI - Risk of internal mammary lymph node metastases and its prognostic value in breast cancer patients. AB - The risk of an internal mammary lymph node (IMN) metastasis and its prognostic value for patients with invasive breast cancer were assessed by evaluating 142 patients who had either a mastectomy with lymph node dissection or a biopsy of the IMN. By univariate analysis, overall survival significantly correlated with the patient's age, clinical axillary node status, tumor size, and DNA ploidy, as well as histologically confirmed axillary and IMN metastases. By multivariate analysis, however, only the presence of axillary and IMN metastases appeared to be an important independent factor affecting survival. However, the incidence of IMN metastases was associated significantly with age, clinical tumor and axillary node status, tumor size, axillary lymph node metastases, and DNA ploidy. Accordingly, the patient's age, tumor size, DNA ploidy, and axillary lymph node metastases proved to be effective variable for discrimination. Consequently, in predicting the presence of IMN metastases, a diagnostic accuracy of 82%, a sensitivity of 84%, and a specificity of 82% can be achieved by a discriminant function. We conclude that the discriminant function with these four variables is effective in assessing the risk of IMN metastases. PMID- 8441258 TI - The significance of ureteral obstruction in invasive transitional cell carcinoma of the urinary bladder. AB - Ureteral obstruction is a frequent complication of transitional cell carcinoma (TCC), known as a poor prognostic sign and indicative of advanced disease. We investigated retrospectively the medical records of 122 consecutive patients who suffered from invasive TCC of the urinary bladder during a 6-year period. Unilateral or bilateral ureteral obstruction was found in 66 patients (54.1%). High stage (T3-T4) and grade (III-IV) tumors were correlated with ureteral obstruction in 89.4% and 83.3% respectively compared to 67.9% and 66.1%, respectively, among patients with normal upper tracts (P < 0.001); 10.6% of the patients with ureteral obstruction had low stage disease, and all of them proved to have involvement of the ureteral orifices on the affected side. The 5-year survival rate of patients with and without ureteral obstruction was 32.2% and 65.9%, respectively (P < 0.001). The presence of ureteral obstruction, particularly in the absence of intravesical involvement of the ureteral orifices, signified a high stage, muscle invasive, and often metastatic tumor in more than 90% of the patients. Ureteral obstruction was an accurate criterion for poor prognostic and was associated with significantly lower, overall and stage specific, survival rates, despite of radical surgery. We conclude that evidence of ureteral obstruction is an important staging standard and significant prognostic indicator in transitional cell carcinoma of the urinary bladder. PMID- 8441259 TI - Surgical treatment of esophageal carcinoma in patients eighty years of age and older. AB - Before 1979, no patient 80 years of age or older had been operated on at our institution for esophageal cancer, while in the middle period (1980-1984), three patients were operated on, and postoperative pulmonary complications and operative death occurred in 66.7 and 33.3%, respectively. However, in the recent period (1985-1990), there was no postoperative morbidity or mortality in the five cases over age 80. On the other hand, there were 12 patients over age 80 who did not undergo operation, of whom all died of cancer. In the eight operated patients over age 80, two cases are still alive 17 and 34 months after operation. According to the above findings, when the patient's general condition is evaluated to be sufficient to tolerate the operation and the cancer is judged to be resectable, esophageal resection is thought to be indicative in all patients over eighty. PMID- 8441260 TI - Complete axillary lymph node dissection. PMID- 8441261 TI - An alternative treatment of anal squamous cell carcinoma: combined radiotherapy and chemotherapy. AB - The conventional surgical treatment of anal squamous cell carcinoma is abdominoperineal resection. A new approach of combined radiotherapy and chemotherapy has been proposed following the observation of excellent local control. In this retrospective study, 40 cases of primary anal squamous cell carcinoma without distant metastasis were collected between 1979 and 1986 and the individual prognosis of the above two methods of treatment was evaluated. Group I (20 cases) received abdominoperineal resection with or without postoperative radiotherapy. Postoperative radiation was given if regional lymph node biopsy was positive. Group II (20 cases) received combined radiotherapy and chemotherapy with or without wide local excision. Radiation was delivered to the anus, pelvis, and bilateral inguinal nodal areas to a total dose of 5,500 rads. A continuous infusion of 5-FU was started on day 2 of the irradiation at a dose of 1,000 mg/m2 body surface/day for 5 days and a bolus injection of mitomycin was given on day 2 at a dose of 10 mg/m2 body surface. The second course was given 1 month later to complete the chemotherapy. The wide local excision was performed if the disease still persisted after completion of combined radiotherapy and chemotherapy. All 40 cases were followed up for at least 5 years. All cases (100%) in group I survived 1 year, 18 cases (90%) 2 years, 14 cases (70%) 3 years, 10 cases (50%) 4 years, and 6 cases (30%) 5 years. Twenty cases (100%) in group II survived 1 year, 17 cases (85%) 2 years, 13 cases (65%) 3 years, 8 cases (40%) 4 years, and 5 cases (25%) survived 5 years. All the mortalities in both groups died of distant metastasis or abdominal carcinomatosis. From the above results, the overall survival rate of combined radiotherapy and chemotherapy was not significantly worse than that of conventional abdominoperineal resection. In conclusion, combined radiotherapy and chemotherapy may be chosen as an alternative management in treating anal squamous cell carcinoma. PMID- 8441262 TI - Colorectal carcinoma: analysis of management in two medical eras. AB - Trends in presentation, diagnosis, management, and outcome were analyzed for 503 patients with colorectal cancer seen at the UCLA Medical Center between 1960 and 1970 (Group A; n = 210) and 1980 and 1985 (Group B; n = 293). Patients in the latter group exhibited a shift in site to the right side of the colon (18% in Group A vs. 31% in Group B; P < .01), an increase in the number of primary resections without colostomy (38% vs. 61%; P < .01), a lower overall complication rate (28% vs. 18%; P = .01), and a decline in 30-day mortality (6.2% vs. 2%; P = .01). Although little difference was seen in detection of asymptomatic tumors, earlier lesions were treated in the latter group, accounting for substantially reduced rate of recurrence (69% in Group A vs. 44% in Group B; P < .01). Future management should include an emphasis on earlier detection in order to continue the trend toward enhanced survival. PMID- 8441263 TI - Carcinoma of the penis: the Indian experience. AB - A total of 150 evaluable patients with carcinoma of the penis were treated at the Tata Memorial Hospital between 1984 and 1987. The majority of patients were in the 4th to 7th decades. All patients presented with a growth on the penis, the biopsy of which revealed squamous carcinoma. The primary lesions were T1 in 34, T2 in 73, T3 in 41, and T4 in 2 patients, respectively. The inguinal nodes were not palpable (N0) in 77 patients, palpable but histologically not metastatic in 39 patients, and metastatic in 34 patients. The treatment of the primary lesion was surgery in 142 patients and radiation therapy in 8 patients. Patients with nonpalpable nodes were kept under surveillance and those with pathologically metastatic nodes were subjected to bilateral ilioinguinal lymphadenectomy. The size related 5 year survivals were 83.3% for T1, 60.4% for T2, and 39.5% for T3 lesions. The 5 year survivals for patients with grade I lesions were 90.3%, for grade II 58.6%, and for grade III 16.7%. The 5 year survival rate for patients for N0 nodes was 75.4% while the 3 year survival rates for patients with N1 and N2 nodes were 40% and 38.8%, respectively. The factors signifying poor survival were perinodal extension and iliac node metastases. There were 8 penile stump recurrences, of which 6 could be salvaged. Metachronous inguinal node metastases developed in 16 patients among whom surgical lymphadenectomy was possible in 12 while 4 had unresectable metastases. PMID- 8441264 TI - A suitable model for experimental liver metastasis of human colon cancer xenografts using mice with severe combined immunodeficiency. AB - Studies on liver metastasis of human colon cancer are limited because of a lack of suitable animal models. In this study, the usefulness of mice with severe combined immunodeficiency (SCID), which congenitally lack functional T and B lymphocytes, was evaluated in comparison with currently available nude mice. Three human colon cancer xenografts transplantable into nude mice were disaggregated enzymatically to obtain tumor cell suspensions, and implanted intrasplenically into SCID and nude mice. The incidence of splenic tumorigenesis and of liver metastases were significantly greater in SCID mice for all xenografts, in comparison with nude mice. In total, 33 of 36 SCID mice and 17 of 43 nude mice developed liver metastases. On the basis of this result, we conclude that SCID mice would be a more suitable model than nude mice for studying liver metastasis of human colon cancer. PMID- 8441265 TI - Choroidal metastasis from primary adenocarcinoma of the esophagus. AB - Primary adenocarcinoma of the esophagus is uncommon and the incidence in the middle third of the esophagus is rare, accounting for about 0.7%-1.5% of cases. Metastasis of carcinoma to the eye is a rare occurrence. We report here a case of primary adenocarcinoma of the middle third of the esophagus with choroidal metastasis. PMID- 8441266 TI - A comparison of the logistic regression and the Cox proportional hazard models in retrospective studies on the prognosis of patients with gastric cancer. AB - To define the independent prognostic factors reducing survival time for gastric cancer, we compared the logistic regression and the Cox proportional hazard models applied to patients who underwent curative gastrectomy. All patients were evaluated after being followed for long fixed periods. Of 1,019, 269 (26.4%) died of tumor recurrence within a 5-year period and 36 (3.5%) died over 5 years after the original surgery. With regard to survival time, multivariate analyses using the Cox proportional hazard model in a stepwise manner adjusted for the sex, age, and 10 other factors, suggested that size of tumor (P < 0.01, relative risk [rr] = 1.0962), degree of gastric wall invasion (P < 0.01, rr < 1.3520), and status of lymph node metastasis (P < 0.01, rr = 1.6572) were the most independent prognostic factors. As well as, using the stepwise logistic regression model, size of tumor, (P < 0.01, odds ratio [or] = 1.115), degree of gastric wall invasion (P < 0.01, or = 1.428), and status of lymph node metastasis (P < 0.01, or = 2.182) were also the most independent risk factors for recurrence within 5 years after surgery. Although regression coefficients are not all the same, these three factors proved significant in both multivariate analyses. This equation for risk factors for prognosis is approached when searching for an appropriate method of retrospective studies using multivariate analyses. PMID- 8441267 TI - CA 19-9 as a prognostic index after resection for pancreatic cancer. AB - Serial serum CA 19-9 assays were performed in 30 consecutive patients who underwent resection for pancreatic cancer. Patients with preoperative CA 19-9 levels < 200 U/ml had significantly better prognosis than those with CA 19-9 > 200 U/ml (P < 0.001). Serum tumor marker normalized in 14 patients after tumor resection, and survival in this group was significantly higher than that of patients with persistently elevated CA 19-9 (P < 0.0001). Prognosis was also influenced by absence of lymph node metastases (P < 0.02) and radicality of resection (P < 0.005). Elevation of serum CA 19-9 levels after operation well predicted tumor recurrence from 1-10 months before clinical and radiological evidence. CA 19-9 determination is useful as a prognostic index after resection for pancreatic carcinoma and as a surveillance test in monitoring the efficacy of treatment. PMID- 8441268 TI - Preimmunization of mice with formalinized extracellular antigens of melanoma in combination with IL-2 and surgical resection increased survival and tumor control in metastatic melanoma model. AB - Recently we found that immunization with formalized extracellular antigens (FECAs) could induce the production of specific antimelanoma antibodies and increase the defense mechanisms of antimelanoma cellular and humoral immunity. In experiments we used pathogen-free female mice C57BL/6 18-20 g. We injected FECA (0.02 mg of protein/per S.C.--subcutaneous injection) for 1 month, once per week. Concurrently we injected S.C. human recombinant IL-2: 100 U/g of weight (2,000 U/per mouse). Interleukin-2 (IL-2) was injected for 1 month, 5 days/week. On days 7, 14, 21, and 28 we took retroorbital blood from mice for the study of anti-FECA and anti-IL-2 antibody production with ELISA. Control and experimental mice were then given a subcutaneous injection with 0.5 x 10(6) cells B16-F10 melanoma in 25 microliters into the middle of the tail. By 18 days 100% developed local melanoma tumors. We resected tails of all control and experimental animals 5 mm distal the base of the tail under metaphan anesthesia. The production of antibodies to FECA and IL-2 started after the 21st day and was higher in the group of mice immunized with FECA and with IL-2 than in control animals. Combining preimmunization with FECA and IL-2 and resection of local melanoma tumors decreased the mortality and the number of mice with local recurrence and metastatic melanoma tumors to the lungs. PMID- 8441269 TI - Exposure of the superior thyroid pedicle during thyroidectomy. PMID- 8441270 TI - Minimizing the blood loss during flap raising in thyroidectomy. PMID- 8441271 TI - Risk of bilateral cervical lymph node metastases in papillary thyroid cancer. AB - We evaluated the risk of bilateral or contralateral cervical lymph node metastases in 135 patients with papillary thyroid cancer who underwent bilateral neck dissection. We confirmed that bilateral jugular lymph node metastases were frequent in patients with obvious carcinoma in both lobes of the gland, in those with cancers arising in the isthmus, in those with clinically detectable bilateral lymphadenopathy, and in those with recurrent thyroid cancer. However, only 24% of the patients who had cancer clinically confined to one lobe with no bilateral or contralateral lymphadenopathy had histologically detected bilateral or contralateral jugular lymph node metastases. But the occurrence of contralateral jugular lymph node metastases was significantly correlated with both clinical lymphadenopathy in the ipsilateral neck and contralateral paratracheal lymph node metastases. Bilateral lymph dissection might be beneficial for these patients. PMID- 8441272 TI - High dose rate intraluminal radiation in a combined modality treatment plan for carcinoma of the esophagus. AB - We have previously reported results for treatment of adenocarcinomas and squamous cell carcinomas of the mid and distal esophagus as well as the use of intraluminal high-dose rate radiation (HDR-RT) for palliation of carcinoma of the esophagus. In this report we describe the results of a chemotherapy/HDR RT/esophagectomy management program. Examination of the surgical specimens revealed a complete response in only 13% of patients and locoregional recurrence was disappointing. There were no operative deaths nor were there major complications attributable to the preoperative treatment. Two-year survival was 33%, only slightly better than that previously achieved by us with either primary surgery or primary external beam radiation among "curative" candidates with locoregional disease. HDR in combination with our selected chemotherapy regimen is insufficient for locoregional control and must be supplemented either by esophagectomy or external beam radiation for even modest long-term survival. PMID- 8441273 TI - Recurrence-associated mortality in patients with differentiated thyroid carcinoma. AB - Differentiated thyroid carcinoma (DTC) is associated with prolonged natural history, and even recurrent tumor is not necessarily followed by increased mortality. Prognostic factors and different treatment strategies, therefore, are difficult to assess. One hundred and fifty-seven patients were followed in our clinic. In an attempt to predict mortality from this tumor, we evaluated the risk factors in 36 patients who presented with recurrent disease. Ten of these patients died. Age above 40 years at initial diagnosis was the predominant risk factor associated with 44% mortality after recurrence. Male sex, lack of radioiodine treatment, and distant site of initial recurrence were all associated with a trend towards increased mortality. Tumor histology and local invasion or extent of initial surgical treatment failed to affect mortality. In conclusion, this approach may be used to identify those patients who will die from their disease, despite currently available treatment. It remains to be seen, however, if new treatment protocols can be developed to improve the prognosis of these patients. PMID- 8441274 TI - Changing role of splenectomy for hematologic disease. AB - In the past decade the development of accurate imaging and the evolution of the medical management of hematologic diseases has led to changes in the indications for splenectomy for these disorders. To assess the impact of these developments, a multi-institutional, retrospective review was undertaken. One hundred fifty-six splenectomies were performed for hematologic disorders between July 1, 1979 and June 30, 1991. Patients were divided into 2 groups: those undergoing splenectomy from 1979-1985 (Period I), and those undergoing splenectomy from 1986-1991 (Period II). Diseases were classified into 3 groups: cytopenic/anemic conditions, symptomatic splenomegaly, and Hodgkin's disease. Data was compared between the two periods using chi-square analysis. More splenectomies were performed for hematologic disorders during Period II than Period I (P < .005). This increase is secondary to a rise in the number of splenectomies performed for cytopenia/anemia during Period II. In contrast, splenectomies for splenomegaly and Hodgkin's disease decreased during Period II (P < .005 and < .05). More Hodgkin's patients were upstaged on the basis of positive laparotomy findings in Period II, compared to Period I (40% versus 10%, P = .01). Surgeons are now performing more splenectomies for cytopenic/anemic diseases, and fewer for splenomegaly and Hodgkin's disease. These results are consistent with recent trends: (1) earlier splenectomy in patients with cytopenia/anemia; (2) earlier medical intervention in infiltrative splenic disorders; and (3) more reliance on radiologic staging in Hodgkin's disease and widespread use of combination chemotherapy, leaving surgical staging for those cases in which treatment would be changed by laparotomy findings. PMID- 8441276 TI - Expression of carcinoembryonic antigen in fresh human gastric cancer cells assessed by flow cytometry. AB - The expression of carcinoembryonic antigen (CEA) by tumor cells from freshly excised human gastric cancers was investigated using flow cytometry (FCM). Highly purified fresh human cancer cells were obtained from solid tumors in 20 patients and from malignant ascites in 6 patients. Thirteen of the 26 tumors were positive for CEA by FCM. CEA expression was more common in well-differentiated tumors than in poorly differentiated tumors. CEA expression was investigated by both FCM and immunohistochemistry in 9 patients, and the two methods agreed in 8 of them. However, quantitative evaluation of CEA expression could only be performed by FCM and not by immunohistochemical staining. FCM could analyze the expression of CEA not only on the cell membrane but also in the cytoplasm, by using gastric cancer cells with or without Triton X-100 treatment. Thus, this study showed that CEA expression can be determined and evaluated quantitatively by FCM. PMID- 8441275 TI - Serum and tissue trace elements in colorectal cancer. AB - Serum copper, zinc, and Cu/Zn ratio were measured using atomic absorption spectrophotometry in 30 patients with colorectal cancer and compared with 30 healthy control subjects. In the patients with colorectal cancer, the tissue copper and zinc levels were also measured in paired histologically normal and malignant colorectal tissue samples obtained at surgery. The mean serum copper levels were higher in patients with colorectal cancer (165.99 vs. 98.84 micrograms/dl) (P < 0.001). The mean serum zinc levels were lowered only in advanced (Dukes stages C and D) colorectal cancer compared to controls (89.94 vs. 115.08 mu/dl) (P < 0.001). However, the Cu/Zn ratio progressively increased with the advancing stage of malignancy (1.86 vs. 0.86) (P < 0.001). The cancerous colorectal tissue showed a higher concentration of both copper (2.78 vs. 1.79 micrograms/g) (P < 0.001) and zinc (27.16 vs. 18.98 micrograms/g) (P < 0.01) compared to non-cancerous colorectal tissue. The exact mechanism responsible for the alterations in trace element levels in patients with colorectal cancer is largely unclear and requires further evaluation. However, the serum copper level and the Cu/Zn ratio are of value in estimating the extent of the carcinoma as well as in determining the prognosis of these patients. PMID- 8441277 TI - Adjuvant chemotherapy for osteogenic sarcoma of the extremity with sequential adriamycin and cisplatin. AB - Twenty-nine patients with high-grade nonmetastatic osteogenic sarcoma of the extremities were treated with adjuvant chemotherapy following definitive surgery. Chemotherapy consisted of systemic intravenous Adriamycin and cisplatin in a sequential fashion given for six courses. Nineteen out of 29 patients are alive and continuously disease free over a follow-up period ranging from 9+ to 30+ months. The relapse-free survival was 72%, and overall survival for the entire group was 69%. Median survival is not reached yet. Six out of 29 patients relapsed, of which 1 patient is alive for 6+ months after relapse. Three patients died of chemotherapy toxicity. The results were superior to historical controls treated with surgery alone. The need for more aggressive treatment approaches is discussed. PMID- 8441278 TI - Hepatic cryosurgery with and without the Bair Hugger. AB - Hypothermia is a significant clinical problem during hepatic cryosurgery, which at times causes the procedure to be halted until the patient's body temperature can be raised. This study examines the effects of the Bair Hugger (a warming device) on body temperature during hepatic cryosurgery. Twenty-eight cases of hepatic cryosurgery were performed without the Bair Hugger, while 44 cases included the Bair Hugger. The lowest mean temperature was significantly lower in the group without the Bair Hugger (34.2 degrees C vs. 35.3 degrees C; P < 0.0001). In addition, this group showed a significantly greater mean change in temperature during the procedure (1.81 degrees C vs. 0.73 degrees C; P < 0.0001). No patient in the Bair Hugger group reached the point of clinically significant hypothermia. In conclusion, the Bair Hugger is safe and very effective in regulating body temperature and it is an essential piece of equipment performing hepatic cryosurgery. PMID- 8441279 TI - Ewing's sarcoma. AB - Between 1984-1987, 50 patients with Ewing's sarcoma of the bone were entered on combined modality protocol at Tata Memorial Hospital. Protocol treatment involved induction therapy consisting of 6-week therapy with vincristine, Adriamycin (doxorubicin), and cyclophosphamide (VDC) followed by local radiotherapy 50 Gy to the involved bone. This was followed for six more cycles of VDC. Five patients had metastatic disease at presentation. Seventy-six percent (38/50) of patients had disease either at axial or proximal site. With a median follow-up of 48 months (range 14-87) 21 patients remained alive with disease-free survival of 38.0% +/- 2.5% at 5 years and overall survival of 36.0% +/- 2.6% at 5 years. Twenty-five patients relapsed with five patients developing local failure and four local and distant metastasis. Using Lee-Desu statistical methods, only response to therapy was a significant factor for survival. We conclude that more aggressive therapy with proper selection of local treatment modality including surgery and/or radiotherapy is required to produce more long-term survival in high-risk Ewing's sarcoma. PMID- 8441280 TI - Malignant arterial tumor embolization. AB - Malignant arterial tumor emboli large enough to cause ischemia or organ infarction are a rare, but often fatal, complication of neoplastic disease. The majority of arterial emboli are associated with primary or secondary pulmonary malignancies. The sites where they impact are similar in distribution to arteriosclerotic emboli, and the treatment follows well-established principles developed for the treatment of arteriosclerotic emboli. The results of embolectomy in accessible sites are very good, thus treatment should always be attempted. A case of a superior mesenteric tumor embolus occurring after pneumonectomy is reported, together with a review of all published cases of arterial tumor emboli of sufficient size to cause organ infarction or ischemia. PMID- 8441281 TI - Malignant pericardial effusion from squamous cell cancer of the cervix. AB - Although rarely diagnosed in women with gynecologic cancers, pericardial metastasis and effusion are often considered preterminal events. As newer therapies result in prolongation of survival for women with advanced cervical cancer, uncommon metastatic sites may be seen with increasing frequency, and warrant increased attention by the gynecologist with oncologic expertise. CASES: Two women with squamous cell carcinoma and symptomatic pericardial effusion, one at initial presentation and the other as recurrent disease, are presented. Following pericardiocentesis, both patients received cisplatinum-based chemotherapy. The patient with effusion at diagnosis survived four months, with recurrent effusion at death. The second patient had no return of cardiac symptoms, with twelve month survival. As demonstrated by the cumulative experience of the six reported cases of this entity, many women with pericardial involvement are candidates for aggressive radiation or chemotherapy. Duration of time from primary therapy prior to occurrence of effusion correlates with survival. PMID- 8441282 TI - [24-hour ambulatory electrocardiographic registry: differences between smokers and non-smokers and habit breaking effects]. AB - BACKGROUND: The purpose of this work was to determine the prevalence of arrhythmias in a group of 90 smokers and to carry out a prospective study on electrocardiographic modifications due to smoking withdrawal. METHODS: A Holter study was performed to 90 smokers and 30 non-smokers. Afterwards smokers were included in a smoking withdrawal program. One year later all subjects who stopped smoking underwent a new Holter study as well as 10 of the smokers who failed in smoking withdrawal. RESULTS: Initial Holter study revealed that smokers had a significantly higher mean cardiac rate (p < 0.001), prevalence of supraventricular arrhythmias (p < 0.01) and ventricular premature complexes (p < 0.05) than non-smokers. Holter study performed after smoking cessation, showed a statistically significant decrease of mean cardiac rate (p < 0.001) and supraventricular arrhythmias (p < 0.001). Holter study performed to the subjects who failed in smoking withdrawal showed no significant changes in relation to the study made the previous year. CONCLUSIONS: Smokers present a higher cardiac rate and prevalence of arrhythmias than non-smokers. From these data it could be suggested that tobacco consumption has an arrhythmogenic effect that can be reverted, at least in part, after smoking withdrawal. PMID- 8441283 TI - [Risk of nosocomial infection in elderly patients admitted to a university hospital]. AB - BACKGROUND: A high percentage of current hospital visits are made by the elderly. The aim of this work is to quantify the risk of contracting a nosocomial infection among elderly patients admitted to a university hospital. METHODS: From the patients admitted from the emergency unit, outpatients and the waiting list, 6 patients of different age groups were chosen each day by a simple random sampling. The criteria of nosocomial infection were those of the CDC. The analysis of the information was made with the programme EPIINFO version 5. The chi 2 tests and Fisher's exact test were used to compare proportions. RESULTS: The rate of nosocomial infection in the group aged over 64 was 14.8%, showing statistically significant differences with respect to other age groups (p = 0.001). In this group the predominant infection was urinary, with an odds-ratio of 3.69, in comparison with the 25 to 44 age group. A prolonged hospital stay (> 15 days) has proved to be closely related to the risk of nosocomial infection in all age groups (p < 0.0001) in patients over 64. CONCLUSIONS: The greater risk of contracting nosocomial infections in the elderly makes it advisable to develop specific prevention programmes for this group, and the fitness of accommodations the length of stay to the care needs suitable to the hospital level. PMID- 8441284 TI - [Resident and intern clinicopathologic conferences]. PMID- 8441285 TI - [Progressive infiltration of cranial nerves as first manifestation of primary meningeal lymphoma]. AB - Primary meningeal lymphomas are an infrequent disease representing 1% of the primary cerebral lymphomas. Progressive paraparesia constitutes the most frequent presentation with progressive infiltration of the cranial nerves being an usual initial manifestation. The case of a primary meningeal lymphoma is presented in a 76 years old patient in whom the form of presentation involved progressive infiltration of cranial nerves. Repeated lumbar punctions demonstrated infiltration of cranial nerves. Repeated lumbar punctions demonstrated inflammatory changes with high protein levels and low sugar levels in cerebrospinal fluid and pleocytosis. No malignant cells were observed upon cytologic study of the LCR. The importance of the determination of tumor markers in LCR and the use of MR with gadolinium in the early diagnosis of this entity is commented upon. PMID- 8441286 TI - [Total body irradiation. Current status]. PMID- 8441287 TI - [A 68-year-old female with acute severe hepatic insufficiency]. PMID- 8441288 TI - [What are we waiting for to reduce the deaths caused by breast cancer?]. PMID- 8441289 TI - [External cerebrospinal fluid diversion and Candida parapsilosis meningitis. Treatment with fluconazole]. PMID- 8441290 TI - [Actol or acfol: confused drug nomenclatures]. PMID- 8441291 TI - [Brucella melitensis: another possible cause of breast abscess++]. PMID- 8441292 TI - [Hypersensitivity to paracetamol]. PMID- 8441293 TI - [Prosody alteration in neurology]. PMID- 8441294 TI - [Intravesical BCG and arthritis]. PMID- 8441295 TI - [Concentration increase of sIL-2R in toxoplasmosis]. PMID- 8441296 TI - Preoperative laboratory testing: should any tests be "routine" before surgery? AB - Routine preoperative testing of all patients before elective surgery is unjustified. The frequency of unanticipated abnormalities or abnormalities shown to change patient management is too low to justify a practice pattern of testing all patients. Furthermore, little evidence exists that test result abnormalities are associated with perioperative morbidity. Table 12 lists a compilation of the findings from this article and recommendations regarding routine testing. PMID- 8441297 TI - What is the value of preoperative pulmonary function testing? AB - This article reviews the current information regarding the value of different tests of lung function in patients undergoing abdominal or thoracic surgery. Risk factors as well as the pathophysiology of postoperative pulmonary complications are also discussed. Finally, a rational approach synthesizing clinical features with pulmonary function test results to estimate risk and minimize complication is presented. PMID- 8441298 TI - Is age a risk factor for surgery? AB - The question of age as a risk factor for surgery is complicated. There are many factors that have an impact on mortality rates in surgical care of the elderly. The most important of these are the physiologic changes with aging, underlying disease states, the type of procedures performed, and whether the procedure is performed as an emergency. Although there are many risks in performing surgery in elderly patients, there are many patients who do well and benefit from undergoing surgical procedures. Age alone should never be used as the criterion to deny surgery indicated in an elderly patient. PMID- 8441299 TI - Is a hemoglobin of 10 g/dL required for surgery? AB - The "10/30" (hemoglobin/hematocrit) rule has long been recognized and accepted in the medical community as the threshold for transfusion in the perioperative setting. However, an increasing number of publications suggest there is no absolute threshold for transfusion, and that this decision should be based on an assessment of the overall clinical picture presented by the patient. This article reviews the risks associated with blood transfusions, and the data in humans and animals that describe the benefits of transfusion. Recommendations on the trigger for red cell transfusion are provided. PMID- 8441300 TI - Is blood pressure control necessary before surgery? AB - The need for blood pressure control before elective surgery depends on the degree and type of hypertension and the presence of other cardiovascular risk factors. Although blood pressure should be normalized in most patients for several months before surgery, mild to moderate diastolic or systolic hypertension do not place the patient at increased operative risk. Mild to moderate elevations should not be acutely controlled in the few days before surgery. Higher blood pressure elevations confer an increased operative risk and must be carefully controlled before surgery. Blood pressure control with certain antihypertensive medications confers a protective effect on the risk of intraoperative instability. The impact of preoperative control of hypertension in relationship to these variables is incorporated into useful recommendations for clinical practice. PMID- 8441302 TI - Cardiac risk stratification prior to vascular surgery. AB - A cardiac etiology is the cause of death in approximately 40% to 60% of patients who die in the early postoperative period following vascular surgery. A variety of modalities has been proposed to identify the patient at risk before the surgical procedure. This article puts these modalities in perspective and discusses the increased risk of cardiac complication for the vascular surgery patient, identifies the patient at risk, and defines methods to decrease patient risk. PMID- 8441301 TI - Ambulatory surgery ... how far can we go? AB - Since its revival in the United States in the 1970s, ambulatory surgery, that intermediate level of care between inpatient and outpatient surgery (with immediate discharge of the patient), has grown phenomenally. During the past decade, the growth has been the result of new surgical techniques, improved anesthetic agents and practices that make such procedures safer, improved and better managed ambulatory surgical facilities, and regulations by government and third-party payers. Consequently, increased utilization of expanded ambulatory surgery appears almost unlimited in the foreseeable future. PMID- 8441303 TI - Update. Deep vein thrombosis and pulmonary embolism prophylaxis in orthopedic surgery. AB - Deep vein thrombosis and pulmonary embolism continue to be controversial areas for prophylaxis in orthopedic surgery. This patient population continues to have the highest incidence of deep vein thrombosis and pulmonary embolism when inappropriately or not prophylaxis for this complication. This article reviews the current modalities for prophylaxis with respect to their safety and efficacy. In addition, the new modalities of low molecular weight heparin and arteriovenous impulse system are presented. PMID- 8441305 TI - Antimicrobial prophylaxis for surgery. AB - Infection of the surgical wound or deep structures violated during surgery account for a major portion of postoperative morbidity. The medical consultant should have an understanding of the principles of antimicrobial prophylaxis for postoperative infection in order to manage this complication in the postoperative period. This article assesses the risks for infection, patient preparation for surgery, and antibiotic usage in frequently performed surgeries. PMID- 8441304 TI - Approaches to the management of cholelithiasis for the medical consultant. AB - Gallstones constitute a major medical problem in the United States. Patients who are asymptomatic require no therapy. Subsequent symptoms develop in a minority of patients, and the need for cholecystectomy is low. Symptomatic patients with reversible risk factors for gallstones, those who refuse surgery, and those who are poor surgical candidates should be considered for medical therapy. Our approach is outlined in Figure 2. Practical options include oral dissolution agents, contact dissolution agents, and shock-wave lithotripsy. Unfortunately, these therapies are successful in very select patients, and only a small percentage of patients with symptomatic gallstones will be candidates for any combination of these. If successful, the recurrence rate is high. Cholecystectomy is a safe, effective procedure that definitively treats symptomatic cholelithiasis. Patients with frequent symptoms of biliary colic, those with severe symptoms, and those who are young and do not have reversible risk factors for gallstones should be considered for cholecystectomy. If surgical expertise is available, the patient requiring an elective cholecystectomy should be educated regarding the laparoscopic approach that offers a better cosmetic result, shorter hospital stay, and faster return to normal activities. The medical consult must be aware of all the options available for managing patients with cholelithiasis. This will afford greater versatility in medical care or perioperative management. PMID- 8441306 TI - Issues in the perioperative care of the patient with psychiatric illness. AB - Several topics have been reviewed pertaining to psychiatric patients requiring either surgery or ECT. Most of the morbidity unique to this group of patients in the perioperative period results from drug side effects or interactions. Complications can be minimized by familiarity with the side effects of psychotropic medication and by the discontinuation of these medications when indicated. PMID- 8441307 TI - Management of the patient with rheumatic diseases going to surgery. AB - This article reviews the perioperative management of rheumatoid arthritis, gout, systemic lupus erythematosus, scleroderma, and ankylosing spondylitis. It discusses the unique interactions between each rheumatologic disease and a surgical challenge and provides guidelines for the assessment of patients preoperatively. The available literature on surgical risks is analyzed, and approaches are suggested to both reduce postoperative complications and control the rheumatic disease. It is hoped that this will aid the internist in evaluating and treating the rheumatic patient undergoing surgery. PMID- 8441308 TI - Advances in perioperative nutritional support. AB - The perioperative period is one of increased metabolic demand and often describes decreased intake. The medical consultant must assist the surgeon in correctly assessing the patient's nutritional status and needs by identifying patients who require nutritional support and managing complications as they occur. PMID- 8441309 TI - Medical consultation in the patient with multiple trauma. AB - Medical consultation is frequently requested to assist the trauma team in the management of the patient with multiple traumatic injuries. Four areas are commonly encountered as problems for management in this patient population. In this article, myocardial contusion, stress ulceration, seizure prophylaxis, and deep vein thrombosis prevention are addressed with respect to incidence, assessment, and management. PMID- 8441310 TI - Intraoperative versus interstitial radiotherapy: a comparison of morbidity in the head and neck. AB - Intraoperative radiation therapy (IORT) and interstitial radiotherapy (brachytherapy) are highly effective adjunctive treatments for head and neck cancer. The radiotolerance of the carotid artery, pharynx, and mandible to therapeutic doses of these modalities, however, has not been clearly established. To investigate the effects of IORT and interstitial iridium 192 (192Ir) on these structures in the canine, both sides of the neck of 12 mongrel dogs were operated on to expose 4-cm segments of the common carotid artery, pharynx, and mandible. One side of the neck was irradiated in each animal with the opposite side serving as the unirradiated control. The animals were divided into 3 groups of 4 dogs each. The first group received 40-Gy IORT and the second, 60-Gy IORT. In the third group of animals, afterloading catheters were implanted followed by placement of 60-Gy 192Ir. At 2 and 4 months after irradiation, 2 dogs in each treatment group were killed and histopathologic examination of the carotid artery, pharynx, and mandible was performed using hematoxylin-eosin staining. No statistically significant difference between treatment groups was found for carotid artery injury, but a trend for the proportion of fibrosis of the carotid on the irradiated side to increase with dose (P = .125) and time (P = .250) was noted. No apparent or statistically significant difference was found between treatment groups for pharyngeal injury. The greatest histologic changes noted following IORT and 192Ir brachytherapy were found in mandible specimens. The incidence of bone marrow suppression in irradiated mandible specimens versus controls approached statistical significance (P = .062). Osteoradionecrosis (ORN) was noted in the irradiated mandible specimens of two dogs, one of which received 60-Gy IORT and the other 60-Gy interstitial 192Ir. This manuscript reviews animal and clinical investigations relevant to the use of IORT and interstitial radiotherapy to the head and neck. Recommendations are made regarding further animal and clinical research as well as methods of treatment. PMID- 8441311 TI - Nasal and paranasal sinus anomalies in children with chronic sinusitis. AB - Functional endoscopic sinus surgery (FESS) is being advocated to treat children with chronic sinusitis. The surgeon performing FESS needs an intimate understanding of the anatomy to adequately treat disease and avoid complications. One hundred thirty-six patients who had endoscopic sinus surgery were reviewed. Preoperative direct coronal computed tomography scans were available for review in 114 patients. Several nasal and paranasal sinus anomalies were uncovered during this evaluation. The most common was hypoplasia of the maxillary sinuses. All hypoplastic maxillary sinuses had diseased mucosa. Eleven patients were found to have a laterally deviated uncinate process and abnormal anatomy of the maxillary ostia. Other anomalies such as concha bullosa, Haller's cells, and paradoxic curvature of the middle turbinate were found, and their respective frequencies in this population were determined. PMID- 8441312 TI - Noise exposure in the rural setting. AB - Noise levels of 155 tractors on 36 farms were studied. The range of noise levels at the driver's ear level with radios off and windows closed (if so equipped) was from 78 to 103 dB. Seventy-five percent of tractors without cabs had noise levels in excess of 90 dB, compared to only 18% of tractors with cabs. The use of a radio adds an average of 3.1 dB of noise. When some cab windows are open and the radio is on, an average of 4.2 dB is added to the cab noise. From the results of this study, the authors recommend hearing protection when time on a tractor with a cab approaches 3 to 4 hours and when time on a tractor without a cab approaches 1.5 to 2 hours. Limited use of the radio is also recommended. PMID- 8441313 TI - Hyperparathyroidism induced by hypothyroidism. AB - The coexistence of hyperparathyroidism and thyroid tumors and/or chronic thyroiditis has raised the possibility of an etiologic relationship. The present study was designed to test the hypothesis that the chronic elevation of thyroid stimulating hormone (TSH) is related to the development of hyperparathyroidism. Three groups of 24 rats each were treated for 12 weeks as follows: group 1 received propylthiouracil (PTU) in their deionized water; group 2 received PTU and thyroid hormone to suppress TSH and to serve as a control group for possible direct effects of PTU; and group 3 was not treated at all and served as another control group. At 12 weeks, 95% of group 1 rats (PTU only) showed hyperplasia of the parathyroids with a 30% mean increase in circulating parathormone. PMID- 8441314 TI - Transpalatal advancement pharyngoplasty for obstructive sleep apnea. AB - Uvulopalatopharyngoplasty (UPPP) is a commonly performed procedure for obstructive sleep apnea (OSA). However, results are inconsistent. Patients in whom the UPPP procedure has failed have a smaller change in airway size as compared to responders, and also many demonstrate continued obstruction at the palate. We present a modification, transpalatal advancement pharyngoplasty, that increases upper oropharyngeal and retropalatal airway size by advancing the soft palate. Eleven patients with severe OSA and multiple sites of airway narrowing were corrected by this method. Three patients had prior UPPP and 5 patients had concomitant tongue-base procedures. Overall results demonstrate clinical enlargement of the retropalatal space. In the 6 patients who had transpalatal advancement pharyngoplasty alone, 4 (67%) were successful responders as defined by a respiratory disturbance index (RDI) of less than 20 events per hour. RDI decreased from 52.8 +/- 12.2 to 12.3 +/- 2.8 events per hour. For the entire group, RDI decreased from 73.3 +/- 29.4 to 25.1 +/- 28.2 events per hour (P < .001). There were four complications, including a transient oronasal fistula(1), transient dysphagia(2), and serous otitis media(1). Transpalatal advancement pharyngoplasty potentially may offer an alternative to increasingly aggressive resection with UPPP in an effort to increase the upper oropharyngeal and retropalatal airway and may be appropriate in careful selected patients as part of the surgical treatment of OSA. PMID- 8441315 TI - Symptomatic versus asymptomatic endolymphatic hydrops: a histopathologic comparison. AB - One of the unanswered questions in Meniere's disease research is the pathophysiology by which the classic symptoms are produced. A histopathological study was undertaken to identify the pathological features of symptomatic endolymphatic hydrops and their relationship to these symptoms. Two groups of temporal bones were examined, compared, and described. The first group was from patients with symptoms of Meniere's disease (n = 29). Temporal bones in the second group were chosen for the presence of endolymphatic hydrops and the absence of otologic symptoms (n = 13). Significant differences were noted in the severity of hydrops, the frequency of membrane ruptures, the endolymphatic duct, and coexistent pathologic conditions. Ruptures were seen in 38% of temporal bones from symptomatic patients and in only 8% of temporal bones from patients with asymptomatic endolymphatic hydrops. Based on this study and a review of the literature, the authors believe that the symptoms and findings of Meniere's disease are explained best on the basis of both chemical and physical mechanisms being operational intermittently and together. PMID- 8441316 TI - Does early expansion surgery have a role in the management of congenital subglottic stenosis? AB - To better define the clinical course of congenital subglottic stenosis, the authors reviewed a cohort of 27 children managed with long-term tracheotomy and interval bronchoscopy. Rates of spontaneous resolution were 19% at 6 months, 39% at 12 months, and 69% at 18 months (Kaplan-Meier survival analysis). Children older than 4 months of age at tracheotomy tended to have more rapid resolution of their stenoses (P = .08). Overall, the median time to decannulation was 15.8 months (95% confidence interval, 13.9 to 17.6 months). One death was possibly tracheotomy-related, and 12 (44%) of the children experienced complications or sequelae resulting in new or extended hospitalization. Considering the prolonged cannulation necessary for spontaneous resolution of congenital subglottic stenosis, the role of long-term tracheotomy as the sole form of management may be limited. Once the need for intervention is apparent, the authors recommend early consideration of cricoid split or laryngotracheoplasty as alternatives to long term tracheotomy. PMID- 8441317 TI - Facial nerve management in cranial base surgery. AB - This study reviewed 124 patients who required facial nerve manipulation during cranial base surgery. Most of them underwent only nerve displacement or selective transection for improved surgical access to the cranial base (70 and 34, respectively). Fourteen patients had the facial nerve resected for oncologic reasons and repaired with primary nerve grafting. Most patients regained quite satisfactory facial function with quality correlating with the degree of nerve injury. Six patients had facial nerve resected as part of oncologic palliation and had the facial deficit rehabilitated with regional tissue. A correlation between preoperative facial nerve weakness and the quality of nerve graft function was not found. An oncologic correlation, however, is suggested (patients with preoperative weakness had less favorable prognosis). Overall, patients who require facial nerve resection for oncologic reasons do not do as well as those with normal preoperative function. PMID- 8441318 TI - Sudden hearing loss induced by acoustic neuroma: significance of small tumors. AB - In our series of 111 patients operated on for acoustic neuroma from 1972 to 1990, 21 (18.9%) had sudden hearing loss. The 21 tumors involved were comprised of 9 small, 5 medium, and 7 large tumors. Emphasis is placed on the fact that even a small tumor has the potential to produce sudden hearing loss (SHL) and that the possibility of seeing patients with SHL is increasing thanks to advances in imaging diagnosis. Recognition of SHL as an initial symptom of acoustic tumor is considered essential to detect small acoustic neuroma. PMID- 8441319 TI - Primary reconstruction of the hypopharynx following pharyngolaryngectomy. PMID- 8441321 TI - Directory of Otolaryngological Societies. PMID- 8441320 TI - Lateral approach to tumors of the craniovertebral junction. PMID- 8441322 TI - Regulation of the M1 muscarinic receptor-Gq-phospholipase C-beta pathway by nucleotide exchange and GTP hydrolysis. AB - M1 muscarinic cholinergic receptors, G1 and G11 (Gq/11), and phospholipase C-beta 1 were highly purified from both natural sources and cells that express the appropriate cDNA's. When the proteins were co-reconstituted into phospholipid vesicles, the receptor efficiently and selectively promoted the activation of Gq/11, leading to marked stimulation of PLC activity in the presence of GTP gamma S. No stimulation was observed in the presence of GTP, however, which led to the finding that PLC-beta 1 stimulates the hydrolysis of GQ/11-bound GTP at least 50 fold. Thus, PLC-beta 1 is a GTPase activating protein, a GAP, for its physiologic regulator Gq/11. We discuss the implications of PLC-beta 1's GAP activity on the M1 muscarinic cholinergic signaling pathway. PMID- 8441323 TI - Phosphorylation of muscarinic receptors: regulation by G proteins. AB - Effects of G proteins on the phosphorylation of muscarinic receptors (mAChRs) have been examined. Cerebral but not atrial mAChRs were phosphorylated by any one of three types of protein kinase C and 4-6 mol of phosphate were incorporated per mol of mAChR, mostly in the 12-14 kDa from the carboxyterminus. Atrial mAChRs were better substrates of cAMP-dependent protein kinase than cerebral mAChRs. Phosphorylation of mAChRs by protein kinase C or cAMP-dependent protein kinase was not dependent on the presence of agonists and G proteins except that a slight inhibition by G proteins was observed probably because G proteins were also substrates of the two kinases. Agonist-dependent phosphorylation of atrial mAChRs or recombinant human mAChRs (m2 subtype) by a kinase (mAChR kinase), which is the same or very similar to beta adrenergic receptor kinase (beta ARK), was found to be regulated by the G proteins in a dual manner; stimulation by G protein beta gamma subunits and inhibition by G protein alpha beta gamma trimer. The inhibition by the G protein trimer is restored by addition of guanine nucleotides and is considered to be due to the formation of a ternary complex of agonist, mAChR and guanine nucleotide free G proteins. The stimulation by G protein beta gamma subunits was also observed for the light- or agonist-dependent phosphorylation of rhodopsin and beta AR by the mAChR kinase but not for the light-dependent phosphorylation of rhodopsin by rhodopsin kinase. The phosphorylation by beta ARK 1 was also found to be stimulated by G protein beta gamma subunits. The beta gamma subunit is considered to interact with the extra 130 amino acid residue carboxyterminal tail of beta ARK, which does not exist in rhodopsin kinase, and the interaction results in the activation of the kinase. We may assume that the G protein coupled receptor kinase is an effector of G protein beta gamma subunits and that one of the functions of beta gamma subunits is to stimulate the phosphorylation of G protein coupled receptors thereby facilitating their desensitization. PMID- 8441324 TI - Regulation of expression and function of muscarinic receptors. AB - The regulation of expression and function of the muscarinic acetylcholine receptor has been studied using several different systems. The role of glycosylation of the m2 receptor was examined by removal of glycosylation sites using site-directed mutagenesis followed by expression in stably transfected cells. The results demonstrated that glycosylation was not required for the synthesis and appearance of the receptors on the cell surface or for the coupling of the receptors to inhibition of adenylyl cyclase activity. Site-directed mutagenesis also was used to demonstrate that the single cysteine in the carboxy terminal domain of the m2 receptor was not required for receptor function, thus rendering unlikely a model suggesting a requirement for palmitoylation of this cysteine in receptor function. The muscarinic receptors expressed in embryonic chick heart were identified by molecular cloning. Two genes were initially identified which are expressed in chick heart and correspond to the chick m2 and m4 receptors. Experiments using the polymerase chain reaction to identify low abundance mRNAs indicate that at least one addition receptor gene is expressed in chick heart. In cell culture, activation of the muscarinic receptors decreases the levels of mRNA encoding the cm2 and cm4 receptors. This probably results from decreased gene transcription due to both mAChR-mediated inhibition of adenylyl cyclase and mAChR-mediated stimulation of phospholipase C. The elucidation of the factors which regulate the expression and function of muscarinic acetylcholine receptors (mAChR) is of obvious importance in understanding the mechanisms underlying cholinergic transmission. In this chapter, we will describe studies on the expression and function of wild type and mutant muscarinic receptors, the molecular characterization of mAChR expressed in chick heart, and the regulation of mAChR gene expression in response to muscarinic receptor activation. PMID- 8441325 TI - m1-toxin. AB - The venom of the Eastern green mamba from Africa, Dendroaspis angusticeps, contains a number of toxins which block the binding of 3H-antagonists to genetically-defined m1 and m4 muscarinic acetylcholine receptors. Most of the anti-muscarinic activity of the venom is due to the presence of a newly-isolated toxin, "m1-toxin", which has 64 amino acids and a molecular mass of 7361 Daltons. At present m1-toxin is the only ligand which is known to be capable of fully blocking m1 receptors without affecting m2-m5 receptors. It binds very rapidly, specifically and pseudoirreversibly to the extracellular face of m1 receptors on cells, in membranes or in solution, whether or not the primary receptor site is occupied by an antagonist. Bound toxin can either prevent the binding and action of agonists or antagonists, or prevent the dissociation of antagonists. The toxin is useful for identifying m1 receptors during anatomical and functional studies, for recognizing and stabilizing receptor complexes, and for occluding m1 receptors so that other receptors are more readily studied. PMID- 8441326 TI - Immunological localization of m1-m5 muscarinic acetylcholine receptors in peripheral tissues and brain. AB - Knowledge of the distributions and functions of native m1-m5 muscarinic acetylcholine receptors in tissues is limited. To characterize the family of m1 m5 proteins directly, a panel of subtype-selective antibodies was generated against divergent i3 loop-fusion proteins. Each antibody was shown to bind a single cloned receptor specifically. In peripheral tissues and brain, four receptor proteins (m1-m4) were found to account for the vast majority of the muscarinic binding sites using immunoprecipitation studies with the subtype specific antibodies. The subtypes were differentially distributed, although most tissues were comprised of a complex mixture of receptors. Moreover, within tissues there were major differences in the precise localization of the subtypes, as determined by immunocytochemistry. The immunological methods described offer a novel approach with exquisite sensitivity and specificity for delineating the distribution of m1-m5 receptors in animal and human tissues. PMID- 8441327 TI - Pharmacological characterization of guanine nucleotide exchange reactions in membranes from CHO cells stably transfected with human muscarinic receptors m1 m4. AB - We have studied muscarinic agonist stimulated [35S]GTP gamma S binding and [gamma 32P]GTP hydrolysis (GTPase) in membranes from CHO cells stably transfected with human muscarinic m1-m4 receptors. 'Full' agonists were at least 10-fold more potent at m2 & m4 receptors than at m1 & m3. This pattern was less marked with 'partial' agonists, which had a greater maximal effect at m2 & m4 than at m1 & m3. McN-A343 uniquely was more potent and efficacious at m4 than at m2 receptors. Antagonist affinity constants were estimated by fitting the data from inhibition curves directly to the Schild model. Antagonist affinity estimates were very similar to those measured earlier in binding studies using animal tissues, and confirmed a small degree of m4 selectivity for tropicamide and secoverine. The receptor subtypes activated more than one G-protein subtype; m2 & m4 receptors activated only pertussis (PTX) sensitive G-proteins, while m1 & m3 coupled to both PTX sensitive and insensitive G-proteins. Acetylcholine (ACh) was more potent in stimulating guanine nucleotide exchange in PTX-treated m1 cells than in controls. PMID- 8441328 TI - WAL 2014--a muscarinic agonist with preferential neuron-stimulating properties. AB - The ability of WAL 2014 to elicit muscarinic responses was investigated in various in vitro and in vivo models. In CHO cells transfected with human m1- or m3- receptor genes, WAL 2014 was clearly more effective in stimulating the M1 mediated PI response. In isolated tissue preparations, WAL 2014 exhibited full agonist properties in the rabbit vas deferens (putative M1 receptor) and behaved like a partial agonist at M2 receptors in the atrium and M3 receptors in the ileum of guinea-pigs. In the pithed rat, in which the increase in blood pressure is mediated through a stimulation of M1 receptors in sympathetic ganglia, WAL 2014 produced a full dose response curve, whereas the reference compounds RS 86 and arecoline exhibited a bell-shaped behaviour. This is in accord with the view that WAL 2014 selectively activates M1 receptors in sympathetic ganglia, whereas conventional agonists in the same dose range stimulate both ganglionic M1 and vascular M3 receptors. The preferential neuron-stimulating properties were confirmed by EEG recording in the rabbit, in which muscarinic activation occurred at doses similar to those for ganglionic stimulation in the pithed rat. On the other hand, higher doses of WAL 2014 were needed to elicit muscarinic effects in peripheral effector organs, i.e. bradycardia, urinary bladder contraction and increase in airway resistance. It is concluded that WAL 2014 due to its preferential neuronal activity is a promising candidate for a cholinergic substitution therapy in Alzheimer's disease. PMID- 8441329 TI - The design of novel muscarinic partial agonists that have functional selectivity in pharmacological preparations in vitro and reduced side-effect profile in vivo. AB - Antagonist/agonist binding ratios (NMS/Oxo-M ratio) were used as an index of the efficacy of novel compounds acting at muscarinic receptors. These binding ratios have been used with a range of functional pharmacological assays to investigate the effects of varying the efficacy of muscarinic agonists. This strategy has been used as a means of obtaining functional receptor selectivity by exploiting differences in effective receptor reserves. The oxadiazole and pyrazine muscarinic agonists L-670,548 (NMS/Oxo-M ratio 1100) and L-680,648 (NMS/Oxo-M ratio 690) are amongst some of the most potent and efficacious agonists known. Decreasing the efficacy of compounds from these series, resulted in compounds with functional selectivity. The chloropyrazine L-689,660 (NMS/Oxo-M ratio 28) was an agonist on the rat superior cervical ganglion (M1), a partial agonist on the guinea-pig ileum (M3), but was an antagonist in the guinea-pig atria (M2). Synthesis of compounds with even lower predicted efficacy, such as the cyclopropyloxadiazole L-687,306 (NMS/Oxo-M ratio 15), maintained agonist activity in the ganglion, but showed antagonist activity in the M3 ileal, as well as the M2 atrial preparations. When tested in vivo these compounds did not produce many of the side effects associated with more efficacious agonists, particularly those associated with the cardiovascular system. However, they were active in reversing scopolamine-induced deficits in a variety of behavioural paradigms. This approach shows how functional selectivity for muscarinic receptor subtypes can be achieved in vitro, that in vivo reduces the dose-limiting side effects normally associated with muscarinic agonists. PMID- 8441330 TI - Therapeutic potential of CNS-active M2 antagonists: novel structures and pharmacology. AB - Clinical trials with muscarinic agonists or acetylcholine esterase inhibitors for the treatment of Alzheimer's dementia have shown disappointing or equivocal results. An alternative treatment of this disease is the development of drugs which enhance the release of acetylcholine. It is believed, that of the five muscarinic receptor subtypes so far identified in the brain, M2 receptors are located presynaptically in the cortex and hippocampus and upon stimulation inhibit the release of acetylcholine. Based on this hypothesis, we initiated a drug discovery program with the aim of identifying selective and centrally active M2 antagonists which are capable of enhancing cholinergic transmission. These efforts resulted in the successful design and synthesis of novel muscarinic antagonists able to cross the blood brain barrier. Moreover, these compounds show few peripheral effects and possess a superior M2 versus M1 selectivity. The prototype of this novel class of M2 selective compounds, BIBN 99, could be a valuable tool to test the hypothesis that lipophilic M2 antagonists show beneficial effects in the treatment of cognitive disorders. PMID- 8441331 TI - Muscarinic receptor subtypes in airways. AB - Muscarinic receptor subtypes in the airways appear to subserve different physiological functions. M1-receptors facilitate neurotransmission through parasympathetic ganglia and enhance cholinergic reflexes, but are also localized to alveolar walls. M2-receptors act as autoreceptors on post-ganglionic cholinergic nerves and inhibit acetylcholine release. There is some evidence that they may be defective in asthma (as a consequence of airway inflammation?) and this may enhance cholinergic reflexes and account for beta-blocker-induced asthma. M2-receptors in airway smooth muscle may also counteract the bronchodilator action of beta-agonists. M3-receptors mediate contractile responses in airway smooth muscle via phosphoinositide hydrolysis, and are the predominant receptors on submucosal glands and airway vascular endothelium. M4- and M5-receptors have not been identified in human airways, but in rabbit lung M4 receptors are expressed on alveolar walls and smooth muscle. Anticholinergic drugs which selectively block M3 and M1-receptors may have an advantage over currently used non-selective antagonists in the treatment of airway obstruction. PMID- 8441332 TI - Effect of inflammatory cell mediators on M2 muscarinic receptors in the lungs. AB - Acetylcholine released from vagal nerve endings constricts airways by stimulating M3 muscarinic receptors on the airway smooth muscle. At the same time, released acetylcholine feeds back onto inhibitory M2 muscarinic autoreceptors on the nerve endings, limiting further release of acetylcholine. Loss of function of these M2 receptors increases vagally-mediated bronchoconstriction after viral airway infections, exposure to ozone, or antigen inhalation. Viral infections may decrease M2 receptor function by inducing inflammation or via direct damage to the receptors as a result of cleavage of sialic acid residues by viral neuraminidase. Inflammation appears to be critical in the loss of M2 receptor function after ozone exposure. Antigen-induced loss of M2 receptor function can be reversed acutely by administering the poly-anionic substances heparin or poly l-glutamate, possibly by binding and neutralizing positively charged eosinophil proteins. Such positively charged eosinophil proteins, particularly major basic protein, may be acting as endogenous inhibitors at the M2 receptors, as can be demonstrated in in vitro ligand binding studies. PMID- 8441333 TI - Ba 679 BR, a novel long-acting anticholinergic bronchodilator. AB - The use of anticholinergics in antiobstructive therapy is well established in pulmonary medicine. We sought to improve the duration of action of inhaled antimuscarinics. A newly developed compound, Ba 679 BR (abbreviated Ba 679) proved to be a highly potent muscarinic antagonist in guinea pig tracheal rings. Its binding to human receptors (Hm1, Hm2, Hm3) was characterized by KD-values in the 10(-10) M concentration range. Assessment of the dissociation rate of complexes of labelled Ba 679 and human muscarinic receptors revealed very slow dissociation in comparison to ipratropium. The half-lives in hours were: Ba 679 Hm3: 34.7, -Hm1: 14.6, -Hm2: 3.6; ipratropium-Hm3: 0.26, -Hm1: 0.11, -Hm2: 0.035. The duration of action in vivo was determined by means of acetylcholine-induced bronchospasms in dogs following inhalation of the drugs. Ba 679 demonstrated a significantly longer duration of protection than an equipotent dose of ipratropium. The plasma levels following inhalation in dogs declined rapidly and are unlikely to reflect the duration of the pharmacological activity. In summary, Ba 679 represents a novel type of antimuscarinic bronchodilator with a long duration of action, most likely due to its slow dissociation from Hm3-receptors. In addition, the drug showed "kinetic receptor subtype selectivity" by having a more rapid dissociation from Hm2 than from Hm1 and Hm3 receptors. PMID- 8441334 TI - Docosahexaenoic acid increases permeability of lipid vesicles and tumor cells. AB - Docosahexaenoic acid (DHA), a long-chain polyunsaturated omega 3 fatty acid, is tested to determine its mode of action as an anti-cancer agent. We demonstrate that DHA can increase the permeability of phospholipid vesicles, as monitored by vesicle swelling in isosmolar erythritol and leakage of sequestered carboxyfluorescein, and T27A tumor cells, as monitored by swelling in isosmolar erythritol and release of sequestered 51Cr. DHA was incorporated into lipid vesicles as either the free fatty acid or as 1-stearoyl-2-docosahexaenoyl-sn glycero-3-phosphocholine. DHA was incorporated into the tumor cells by fusion with vesicles made from the mixed-chain phosphatidylcholines. DHA is demonstrated here to be much more effective in increasing permeability than is oleic acid, the major unsaturated fatty acid normally found in tumor plasma membranes. It is proposed that incorporation of DHA makes tumor plasma membranes substantially more permeable, which may explain, in part, its anti-tumor properties. PMID- 8441335 TI - Hypertension in rats does not potentiate hypercholesterolemia and aortic cholesterol deposition induced by a hypercholesterolemic diet. AB - The effect of a hypercholesterolemic diet (HCD) on hyperlipemia and atherogenesis was investigated using normotensive Wistar/Kyoto rats (WKY), spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP), with systolic blood pressures increasing in that order. Feeding an HCD diet containing cholesterol, cholate and suet induced hypercholesterolemia in all the strains examined as compared with a normal diet. The plasma cholesterol levels were significantly higher in WKY than in SHR and SHRSP fed the HCD diet. The HCD diet also induced hepatic fat deposition, particularly deposition of cholesteryl esters, a slight increase in aortic cholesterol deposition, and elevation of both monoenoic/saturated fatty acid ratios and linoleate/arachidonate ratios in tissue lipids. The changes induced in the three strains by the HCD diet were not positively correlated with blood pressures. The HCD diet affected hepatic acyl CoA:cholesterol acyltransferase and plasma lecithin:cholesterol acyltransferase activities differently in WKY and SHR which, in addition to the induction of delta 9 desaturase, may partly account for the difference in the diet-induced changes in the fatty acid compositions of plasma cholesteryl esters. The results indicate that hypertension per se does not stimulate the development of hypercholesterolemia and arterial cholesterol deposition induced by an HCD diet, suggesting that other factors are involved. PMID- 8441336 TI - The relationship between fatty acid peroxidation and alpha-tocopherol consumption in isolated normal and transformed hepatocytes. AB - The response of normal and transformed rat hepatocytes to oxidative stress was investigated. Isolated normal rat hepatocytes and differentiated hepatoma cells (the Fao cell line was derived from the Reuber H 35 rat hepatoma) in suspension were incubated with the ADP/Fe3+ chelate for 30 min at 37 degrees C. Membrane lipid oxidation was assessed by measuring (i) free malondialdehyde (MDA) production by a high-performance liquid chromatography (HPLC) procedure, (ii) membrane fatty acid disappearance as judged by capillary gas chromatography, and (iii) alpha-tocopherol oxidation as determined by HPLC and electrochemical detection. The addition of iron led to increased MDA production in normal as well as in transformed cells, and to simultaneous consumption of polyunsaturated fatty acids (PUFA) and alpha-tocopherol. In addition, in Fao cells more alpha tocopherol was consumed during lipid peroxidation while less PUFA was oxidized. Lipid peroxidation was lower in tumoral hepatocytes than in normal cells. This could be due to a difference in membrane lipid composition because of a lower PUFA content and a higher alpha-tocopherol level in Fao cells. During oxidation, Fao cells produced 1.5 to 2 times less MDA than normal cells, while in the tumoral cells the amount of oxidized PUFA having 3 or more double bonds was 7 to 8 times lower. Therefore, measuring MDA alone as an index of lipid peroxidation did not allow for proper comparison of the membrane lipid oxidizability of transformed cells vs. the membrane lipid oxidizability of normal cells. PMID- 8441337 TI - Reduction of fatty acid hydroperoxides by human parotid saliva. AB - Arachidonic acid hydroperoxide (15-hydroperoxyeicosatetraenoic acid; 15-HPETE) was introduced into human parotid saliva and incubated at 37 degrees C. Straight phase high-performance liquid chromatography analysis of the reaction mixture showed that 15-HPETE was detoxified to its reduced form, 15 hydroxyeicosatetraenoic acid, in the presence of glutathione. Therefore, it is concluded that human parotid saliva possesses fatty acid hydroperoxide-reducing ability. However, its effectiveness was found to be lower than that of blood plasma. PMID- 8441338 TI - The identification of the allylic nitrite and nitro derivatives of methyl linoleate and methyl linolenate by negative chemical ionization mass spectroscopy. AB - The autoxidation of polyunsaturated fatty acids is initiated both in vivo and in vitro by nitrogen dioxide. The mechanism of the initiation process is believed to involve both addition reactions and hydrogen atom abstraction reactions, with hydrogen abstraction predominating at low levels of nitrogen dioxide. Therefore low levels of nitrogen dioxide should react with polyunsaturated fatty acids to give allylic derivatives; in an anaerobic system these derivations should be allylic nitro and nitrite compounds. Using negative methane chemical ionization mass spectrometry and other analytical techniques, we have identified these allylic nitrite and nitro compounds from the reactions of low levels of nitrogen dioxide with methyl linoleate and methyl linolenate in the absence of oxygen. PMID- 8441339 TI - Determination of 4-hydroxynonenal by high-performance liquid chromatography with electrochemical detection. AB - 4-Hydroxy-trans-2-nonenal (HNE) is a highly reactive product of lipid peroxidation originating from the break-down of phospholipid-bound polyunsaturated fatty acids of cellular membranes. Despite its biological relevance, this aldehyde is only occasionally determined due to the complexity of previously described procedures. Here we present a simple and very sensitive method for the detection of HNE in biological samples. The method is based on the measurement of the 2,4-dinitrophenylhydrazone (DNPH) of the aldehyde by electrochemical detection after separation by reverse-phase high-performance liquid chromatography (HPLC). The greater sensitivity of this procedure as compared to the ultraviolet detection method commonly employed to measure DNPH derivatives of aldehydes after HPLC will allow the detection of HNE below the pmol level. The detection of HNE is highly reproducible even in normal tissues and cells. Increased amounts of HNE were detected in the livers of animals intoxicated with prooxidant agents such as carbon tetrachloride, bromotrichloromethane or bromobenzene. An exponential increase in HNE (and in malondialdehyde) was measured in peroxidizing liver microsomes (in the NADPH/Fe dependent system). The method is also suitable for the study of very small samples, since HNE could be detected in approximately 1 million cultured cells (polyoma virus-transformed baby hamster kidney fibroblasts); the level rose after exposure of the cells to a Fe3+/ADP prooxidant system. PMID- 8441340 TI - Microplate methods for determination of serum cholesterol, high density lipoprotein cholesterol, triglyceride and apolipoproteins. AB - Microtiter plate methods were developed for the enzymatic determination of serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and triglyceride (TG), and for the turbidometric determination of apolipoproteins. The micromethods resulted in accurate, precise values that were in good agreement with the conventional spectrophotometric assays. The coefficient of variation for TC determinations was 4.5% or less and bias was 5% or less. The lipid micromethod assays are sensitive to 10 mg/dL or less, and the apolipoprotein assay to 1 mg/dL. Less than 100 microL of serum suffices for TC, TG and apoprotein assays; HDL-C requires an additional 100 microL of serum. Advantages of the micromethods include reductions in assay time and in the amount of reagents required. PMID- 8441341 TI - A lack of correlation among fatty acids associated with different lipid classes in human milk. AB - The fatty acids associated with triacylglycerol, cholesteryl ester, phosphatidylethanolamine, phosphatidylcholine and sphingomyelin in human milk were compared. Ten milk samples were selected for lipid class analysis based on their total lipid polyunsaturated/saturated fatty acid ratio (P/S ratio). The P/S ratio of the selected milk samples ranged from 0.3 to 0.8. Linoleic acid was the predominant fatty acid in milk to affect the P/S ratio. The percentage of linoleic acid in milk triacylglycerol was correlated (r = 0.84, P < 0.05) with the total milk lipid P/S ratio. Linoleic acid esterified to cholesterol was not correlated with total milk lipid P/S ratio but was correlated (r = -0.66, P < 0.05) with the quantity of lipid in the milk. Linoleic acid in the phospholipid classes did not correlate with shift in P/S ratio of the total milk lipid or linoleic acid content of other lipid classes. PMID- 8441342 TI - Overexpression of a Rhizopus delemar lipase gene in Escherichia coli. AB - A cloned complementary deoxyribonucleic acid encoding the precursor polypeptide of an extracellular lipase from the fungus Rhizopus delemar was altered by site directed mutagenesis to generate deoxyribonucleic acid fragments that specifically code for the polypeptides of the proenzyme and the mature form of the lipase. Attempts to produce these polypeptides in enzymatically active form in Escherichia coli revealed toxic effects toward the host. Therefore the polypeptides were expressed as inactive and insoluble forms in the cytoplasm of E. coli BL21 (DE3) cells using plasmid vector pET11-d. With this tightly regulated high-level expression system, lipase and prolipase polypeptides were produced to estimated levels of up to 21% and 15%, respectively, of total cellular protein. The insoluble polypeptides were solubilized in 8 M urea. Refolding into active forms was achieved by treatment with the redox system cystine/cysteine and dilution. Refolded mature lipase was purified to homogeneity by affinity and ion exchange chromatography. The enzyme had a specific activity comparable to that of lipase from the fungal culture. The quantities of pure enzyme obtained from a 1-L culture of E. coli exceeded those obtained from the fungal culture by a factor of at least 100. Refolded recombinant prolipase was purified essentially to homogeneity and had a specific activity similar to that of the mature enzyme. Its pH optimum was 7.5, rather than the pH 8 determined for recombinant mature lipase and for the enzyme purified from the fungal culture. Recombinant prolipase retained activity after 15 min incubation at 65 degrees C, while mature lipase retained activity only up to 45 degrees C. PMID- 8441344 TI - Medicine is an aspect of civilization: lessons from the Hippocratic medicine. PMID- 8441343 TI - Fatty acid synthesis from [2-14C]acetate in normal and peroxisome-deficient (Zellweger) fibroblasts. AB - The incorporation of [2-14C]acetate into the lipids of normal and peroxisome deficient (Zellweger's syndrome) skin fibroblasts was examined. Most of the label was incorporated into triacylglycerol fatty acids in normal as well as Zellweger's syndrome cells. Triacylglycerols and cholesteryl esters in Zellweger's syndrome cells contained increased levels of labelled saturated and monounsaturated very long-chain fatty acids (VLCFA, that is fatty acids with more than 22 carbon atoms), in particular hexacosanoic (26:0) and hexacosaenoic (26:1) acids. As traces of labelled VLCFA with up to 32 carbon atoms were detected in triacylglycerols even in control cells it is probable that these fatty acids are formed naturally during the elongation process. Our data suggest that peroxisomes are involved in the chain shortening of the saturated and monounsaturated VLCFA. PMID- 8441345 TI - History of microsurgery--from the beginning until the end of the 1970s. AB - Fine surgeries were started by vascular surgeons in the mid 1500s and included vascular ligature or suture of vascular wounds incurred in battle. Between 1800 and 1900, vascular end-to-end or end-to-side anastomoses and autogenous vein grafts became possible due to the efforts of Eck, Carrel and Guthrie. Thereafter, several experiments were performed for the transplantation of organs and limbs. Since the first use of the monocular microscope for ear surgery by Nylen in 1921 and the use of the binocular microscope by Holmgren in 1923, true microsurgery has developed and has gradually been specialized for every clinical discipline including otorhinolaryngology, ophthalmology, brain-neurosurgery, orthopedic surgery, plastic surgery, transplantation surgery, oncology, gynecology and urology. This could not have been accomplished without the development of the Zeiss operating microscope (OpMi system), fine microinstruments, and fine suture materials. The author describes the history of microsurgery from its beginning through the end of the 1970s, covering as many surgical disciplines as possible. PMID- 8441346 TI - 1992 news from Washington. PMID- 8441347 TI - Going "all out" pharmacologically? A re-examination of Berkman and Meyer's "alternative strategies and multiple outcomes in remediation of severe self injury: going 'all out' nonaversively". AB - Berkman and Meyer (1988) is frequently cited as evidence of the effectiveness of positive-oriented programming approaches and in opposition to aversive procedures. In that report, Berkman and Meyer attributed reductions in a client's self-injurious behavior to their intervention. They appeared to rule out the possibility that medication could have been responsible for behavior changes by reporting that medication was held constant during their intervention. We have recently obtained medication records indicating that (a) Berkman and Meyer incorrectly reported their client's medication status during their intervention and (b) there appears to have been a relation between the introduction of Thorazine (with subsequent increases in dosage) and reductions in the client's self-injurious behavior. PMID- 8441348 TI - Special Olympics: an evaluation by professionals and parents. AB - Attitudes toward Special Olympics were examined in a group of 41 experts in the field of mental retardation and 40 parents of participants in the Special Olympics program. Experts completed a 15-item questionnaire that included Likert type items regarding possible Special Olympics goals and their importance and fulfillment and open-ended questions regarding program benefits, strengths and weaknesses. Experts were also asked how the program might fit into the normalization debate. Parents were given a similar survey that also included child and parent participation questions. Generally, both groups viewed the program as highly beneficial, particularly in terms of social adjustment and life satisfaction. As to concerns cited, some experts noted potentially segregative aspects of the program, whereas parents focused on administrative issues. PMID- 8441349 TI - Gilles de la Tourette disorder among individuals with severe or profound mental retardation. AB - There have been limited reports on the incidence of Gilles de la Tourette disorder among individuals with mental retardation. Only three cases have been reported in people with severe or profound mental retardation. In this paper three additional case reports of people with severe or profound mental retardation and Tourette disorder were presented. Issues related to the diagnosis of Tourette disorder in this population were discussed. PMID- 8441350 TI - State MR/DD agency information systems and available data related to day and employment programs. AB - The current status of state mental retardation/developmental disability agency information systems related to day and employment programs for persons with disabilities was described, and data regarding the number and characteristics of persons served in different day-employment programs and the funding sources for these persons were summarized. Suggestions were made regarding data utilization and information systems design. PMID- 8441351 TI - Chernobyl nuclear catastrophe and the high risk potential for mental retardation. AB - The nuclear explosion at Chernobyl nuclear reactor on April 26, 1986, continues to have wide political, social, and medical ramifications. Hot debris from the Chernobyl reactor covered an area of more than 5,000 square kilometers with nearly 20 million curies of radionuclides. Eleven regions with a population of nearly 17 million people, of whom 2.5 million were children below the age of 5 years, suffered some degree of radioactive contamination. These children are currently of elementary school age. One of the tragedies of the explosion is that thousands of these children are at high risk for mental retardation and learning disorders. PMID- 8441352 TI - Cost-effectiveness of supported employment. AB - Monetary costs and benefits of supported employment to individuals, taxpayers, and society were assessed as was the cost-effectiveness of the nonmonetary benefit, namely, quality of life of employees, as a result of supported employment. Participants were 20 individuals from two Central Illinois agencies serving clients with developmental disabilities. Costs and effects were evaluated using benefit-cost and cost-effectiveness analyses. Supported employment was found to be cost-beneficial from the perspectives of the supported employee, the taxpayer, and society over a 5-year period as programs move from sheltered employment. In addition, supported employment was also more cost-effective with regard to quality of life than was sheltered employment. PMID- 8441353 TI - An experimental assessment of facilitated communication. AB - This report presents a quantitative study of facilitated communication. Participants were 12 people living at an institutional autism program and 9 people who provided them with facilitated communication support. These subjects were the 12 most competent producers of facilitated communication in the program. They were shown pictures of familiar objects and asked to type the names of the objects under three conditions: (a) assisted typing with facilitators unaware of the content of the stimulus picture, (b) unassisted typing, and (c) a condition in which the participants and facilitators were each shown pictures at the same time. In this last condition the paired pictures were either the same or different, and the participant's typing was facilitated to label or describe the picture. These participants were unable to succeed in the tasks without facilitator assistance. On trials when the facilitators and participants had different pictures, the only "correct" labels were for pictures shown to the facilitators and not shown to the participants. This finding demonstrates that the facilitators were unknowingly determining what was typed. PMID- 8441354 TI - Four different types of glucans synthesised by glucosyltransferases from Streptococcus sobrinus. AB - Four different kinds of glucosyltransferases (GTFs) were purified from the cariogenic bacterium Streptococcus sobrinus AHT. One of them (GTFP3) produced water-insoluble glucan with the alpha-1,3 linkage, exclusively. The others (GTFP1, P2 and P4) produced water-soluble glucans. GTFP2 produced oligosaccharides with linear 1,6-alpha-D-glucan structure. Since GTFP1 and P4 produce similar molecular weight glucans, the structural differences between these glucans remain unclear. To clarify the difference between GTFP1 and P4 products, the glucan structures were investigated by methylation analysis with gas liquid chromatography and gas liquid chromatography-mass spectrometry. The glucan synthesised by GTFP1 was 1,6-alpha-D-glucan with a high percentage (25.9 mol%) of 1,3-alpha-D-linked units. The other glucan synthesised by GTFP4 contained 1,6-alpha-D-glucan with 1,3,6-alpha-D-glucose (18.5 mol%). PMID- 8441355 TI - An arginine residue at the active site of beta-lactamase from Shigella flexneri UCSF-129. AB - The role of a residue of arginine at the active site of beta-lactamase from Shigella flexneri UCSF-129 was studied. It is a local pathogenic strain which produces intestinal problems, especially in children. Purified enzymes were obtained by affinity chromatography on phenylboronic acid-agarose gels. The enzyme was serine dependent with a molecular weight of 23.6 kD. It was specifically modified with phenylglyoxal (1/830 molar ratio) and incubated for 20 min in the presence of 50 mM sodium phosphate buffer at pH 8.3. The chemical change was established by isoelectric focusing, since a loss of one positive charge was detected. Protection by cephradine, a substrate, indicated the presence of a residue of arginine at its active site. Controls were conducted by differential spectroscopy. Similar results were obtained with 2,3,butanedione. This vital arginine stabilizes the negative charge of the carboxylic group of C-3 or C-4 from the substrates. PMID- 8441356 TI - Types of bacteria found in the canals of Amsterdam. AB - The bacteriological quality of the canal system in Amsterdam was assessed by determination of the quantity and quality of the water. Eight samples of water from different canals were studied. No Gram-positive bacteria were found. The number of Gram-negative bacteria varied from 720-1,820 (average 1,250) organisms per ml of water. The predominant bacteria were: Pseudomonas sp., Klebsiella pneumoniae and Escherichia coli. These data illustrate the high number of potential pathogens in the water canal system in Amsterdam. PMID- 8441357 TI - Polyamine metabolism in Acanthamoeba culbertsoni. AB - 1,3-Diaminopropane has been identified as the major polyamine of Acanthamoeba culbertsoni. N-acetylputrescine and spermidine were present in appreciable amounts and putrescine as well as N-acetylspermidine were also detected, but spermine was absent. Changes in polyamine levels were observed during the growth of amoebae. Ornithine decarboxylase activity was detected in cell-free extracts but there was very low activity of arginine and lysine decarboxylases. A potent polyamine oxidase was demonstrated which preferentially acted on N8-acetyl spermidine as the substrate while N1-acetylspermidine was a poor substrate; free polyamines did not serve as a good substrate for this enzyme. Active uptake of polyamines by the amoebae was also demonstrated. PMID- 8441358 TI - [What can pharmacology present to the pharmacist in the future?]. PMID- 8441359 TI - [Therapy with pancreatic enzyme preparations]. PMID- 8441360 TI - [Hormone therapy in the climacteric of women]. PMID- 8441361 TI - [Advancements in gene therapy]. PMID- 8441362 TI - Flosequinan for heart failure. PMID- 8441363 TI - Paroxetine for treatment of depression. PMID- 8441364 TI - Choice of an antidepressant. PMID- 8441365 TI - The history of behavioral neurology. AB - Although often considered to be a relatively new subdivision of neurology, behavioral studies actually have a long and colorful history. The events that led originally to a consideration of behavior as a neurologic subspecialty are outlined, followed by a listing of some of the major occurrences and key figures that have produced the considerable growth of behavioral neurology over the past two decades. PMID- 8441366 TI - Behavioral changes associated with epilepsy. AB - Epilepsy can be accompanied by changes in cognition, personality, affect, and other elements of behavior. There is no single epileptic constitution or personality complex. A unifying theme to the behavior in epilepsy is diversity. As one looks at the behavioral traits reported in epilepsy, a specific and consistent pattern is lacking. Rather, extremes of behavior are accentuated: sometimes in one direction, often in both directions. Changes in emotional state are prominent among behavioral features in epilepsy. Some authors describe a prominent deepening or increase in emotionality, whereas others identify a global decrease in emotional life and content. Emotional lability is also reported. Sexuality and libido are typically decreased, but fetishism, transvestism, exhibitionism, and hypersexual episodes also occur. Concerns over morality may be lacking or exaggerated. Patients may be irritable and aggressive or timid and apathetic. The impressive list of people with epilepsy in politics, religion, arts, and sciences suggests a positive expression of this behavioral spectrum. Psychosis, depression, paranoia, and personality disorders may represent a negative pole of epilepsy-related behavioral changes. The most important aspect of behavioral changes in epilepsy for physicians is to recognize and treat dysfunctional behavior. Depression is a common problem that is often unrecognized and untreated. Other treatable problems include impotence, anxiety, panic attacks, and psychosis. Identifying risk factors will, it is hoped, assist in developing methods to prevent these disorders. PMID- 8441367 TI - Seizure benefit: grand mal or grand bene? AB - The adverse stresses and injuries associated with epileptic seizures are prevented routinely when programmed, controlled grand mal seizures are administered. According to the described concepts of clinical benefit, symptoms of brain illnesses that are without substantial neuronal deterioration, but that have a sense of neurotransmitter dysregulation, are candidates for mitigation by administration of programmed seizures. Such symptoms include delirium, dementia, neuroleptic malignant syndrome, movement disorder, psychosis, and depression. Prior to recommending cortical excision for management of offtial complex epilepsy, a course of programmed seizures should be considered routinely. PMID- 8441368 TI - Neuroanatomic basis of developmental dyslexia. AB - This article reviews the known neuroanatomic and neuropathologic bases of developmental dyslexia in the context of some of the functional deficits exhibited by affected individuals. Observations from autopsy brains and experimental animal models disclose problems with cerebral asymmetry, focal developmental disorders affecting the cerebral cortex, and abnormalities in the magnocellular pathway of the visual system. PMID- 8441369 TI - The contribution of neuropathologic studies to the understanding of autism. AB - A review of the neuropathology of infantile autism shows abnormalities in the limbic forebrain and in cerebellar circuits. The role of the cerebellar lesions in the symptomatology of infantile autism is unknown. The cerebellar findings appear to date from a fetal stage of development with evidence for an ongoing process after birth. The timing of the findings in the limbic system is unknown. A postulated role for these findings in the limbic system in infantile autism is presented. PMID- 8441370 TI - Cognitive and emotional disturbances in multiple sclerosis. AB - The nature, prevalence, and course of cognitive and emotional disturbances in multiple sclerosis (MS) are described in this article. Mild to moderate cognitive impairment is common in MS and may be more incapacitating than physical symptoms for some patients. Although existing neurologic and neuroimaging procedures can detect some cognitively impaired patients, they lack sensitivity. Development of a brief neuropsychological screening battery, suitable for routine clinical use, is an important objective that may be achieved in the near future. PMID- 8441371 TI - Neurobehavioral sequelae of alcoholism. AB - Chronic alcohol abuse is associated with a wide range of cognitive deficits, including impairment in perceptual-motor skills, visual-spatial functions, learning/memory, and abstraction and problem solving. In Korsakoff patients, despite normal IQs, these deficits are pronounced, especially in episodic memory and new learning. Procedural memory (learning of simple, repetitive skills), however, is relatively intact. New evidence suggests that orbitobasal frontal lobe dysfunction in addition to diencephalic lesions contributes to the deficits found in Korsakoff patients. A genetically controlled thiamine deficiency has been hypothesized to account for the development of the Wernicke-Korsakoff disorder. Prognosis for the recovery from Korsakoff's syndrome is poor, although evidence suggests that these patients should be able to learn simple repetitive tasks involving procedural memory. In non-Korsakoff sober alcoholics the aforementioned cognitive deficits are less severe but nonetheless significant. These performance deficits are not easily accounted for by the current neuropsychologic hypotheses, although neuroanatomic changes frequently accompany chronic alcohol abuse. Family history, although a significant predictor of later alcoholism, does not appear to play a major role in determining alcohol-related cognitive deficits. A history of childhood behavioral disorders is associated with greater cognitive impairment. The means by which its effect is expressed, however, is unclear. The most parsimonious explanation focuses on the possibility that these disorders are the manifestation of inherited temperament traits that increase vulnerability to a variety of negative outcomes including antisocial personality and alcoholism. Significant recovery of cognitive function can occur but may be contingent on factors such as age and continued abstinence. PMID- 8441372 TI - Uses and abuses of neuropsychological testing in behavioral neurology. AB - This article provides a brief historical review of how psychological tests have been used to examine patients with brain dysfunction and summarizes the strengths and weaknesses of present-day neuropsychological testing procedures. Common uses and abuses of neuropsychological testing are listed with a few clinical examples. PMID- 8441373 TI - Elements of cognitive rehabilitation after right hemisphere stroke. AB - There are two basic approaches to cognitive training: (1) impairment training and (2) task specific training. Impairment training addresses impairments common to a number of tasks and attempts to offer a general benefit to all of the tasks at once. Task specific training focuses on the impairments that arise in a single task and attempts to improve performance on that task. Impairment training of spatial disorders following right hemisphere stroke has shown some success when curricula are properly designed. The success, however, is quite limited because of normal cognitive constraints and those occurring after brain damage. Task specific training in conjunction with the combined application of various cognitive principles appears more promising, but as yet, only a few studies exist. The neurologic factors are likely to be the same factors that influence recovery. The factors that influence trainability are lesion topography (size and location of the focus plus premorbid atrophy), lesion chronicity, and the presence of additional cognitive impairments (anosognosia, confusion, and abulia). Other interventions that may be beneficial, even for training resistant patients, include behavior modification, cognitive prostheses, and drugs. PMID- 8441374 TI - Vigilance and its disorders. AB - Vigilance has been defined as steady-state alertness-wakefulness. The right cerebral hemisphere, predominantly the right inferior parietal lobule and posterior parietal cortices, seems specialized for vigilance. Studies of the primary disorder of vigilance, a genetically determined condition, should provide a better understanding of the neurobiology of vigilance. Common causes of secondary hypovigilance (depression, learning disability, narcolepsy, and acquired focal right cerebral hemisphere brain lesions) explain the symptom complex of ADHD. If these specific entities producing hypovigilance are correctly identified, treatment is successful and with favorable outcome. The neuroanatomic substrate of lowered vigilance seems to be loss of modulating influence of the right cerebral hemisphere on the diencephalon and select brain stem nuclei. We propose that the right (more than the left) cerebral hemisphere is responsible for alertness and wakefulness (vigilance) with the reticular formation being accountable for sleep. PMID- 8441375 TI - Is depression a neurologic disease? AB - There is now ample evidence that depression produces observable changes in a variety of brain systems that should be of interest to investigators and clinicians in neurology. Thus neurologists should take the lead in providing comprehensive assessment of the clinical, neurophysiologic, neuropsychologic, neuropharmacologic, neurochemical, neuroimaging, and neuropathologic changes occurring in depression. In addition, because depression is a treatable condition, clinicians should make every attempt to identify the disorder and institute appropriate therapy to maximize neurologic benefit for the patient. PMID- 8441376 TI - Nonverbal aspects of language. AB - This article describes the recently discovered language functions of the right hemisphere that involve the (nonverbal) modulation of affective prosody and gestures. The organization of these functions, at a syndomic level, appears to be analogous to the organization of verbal language in the left hemisphere. The relationship of the affective aspects of language and communication with general emotions and the neurology of poststroke depression are discussed also. PMID- 8441377 TI - Dimerization of NF-KB2 with RelA(p65) regulates DNA binding, transcriptional activation, and inhibition by an I kappa B-alpha (MAD-3). AB - Inducible expression of human immunodeficiency virus (HIV) is regulated by a cellular transcription factor, nuclear factor kappa B (NF-kappa B). NF-kappa B is composed of distinct subunits; five independent genes, NFKB1(p105), NFKB2(p100), RelA(p65), c-rel and relB, that encode related proteins that bind to kappa B DNA elements have been isolated. We have previously found that NFKB2(p49/p52) acts in concert with RelA(p65) to stimulate the HIV enhancer in Jurkat T-leukemia cells. Here we examine the biochemical basis for the transcriptional regulation of HIV by NFKB2. Using Scatchard analysis, we have determined the dissociation constants of homodimeric p49 and heterodimeric p49/p65 for binding to the HIV kappa B site. p49 has a approximately 18-fold-lower affinity for the HIV kappa B site (KD = 69.1 pM) than does the approximately 50-kDa protein NFKB1(p50) derived from p105 (KD = 3.9 pM). In contrast, the affinity of heterodimeric NFKB2(p49)/RelA(p65) for this site is approximately 6-fold higher (KD = 11.8 pM) than that of p49 alone. Consistent with these findings, in vitro transcription was stimulated 18 fold by the addition of preformed, heterodimeric NFKB2(p49)/RelA(p65) protein. Transcriptional activation of the HIV enhancer was also subject to regulation by recently cloned I kappa B-alpha(MAD-3). Recombinant I kappa B-alpha(MAD-3) inhibited the DNA binding activity of p65, p49/p65, and p50/p65 but stimulated the binding of NFKB2(p49) or NFKB1(p50). Functional activation of an HIV reporter plasmid by p49/p65 in transiently transfected Jurkat T-leukemia cells was also inhibited by coexpression of MAD-3. These data suggest that binding of the NFKB2 subunit to the HIV enhancer is facilitated by RelA(p65) and that this NFKB2(p49)/p65 heterodimeric complex mediates transcriptional activation which is subject to regulation by MAD-3. PMID- 8441378 TI - Factors affecting authentic 5' splice site selection in plant nuclei. AB - To define elements critical for 5' splice selection in dicot plant nuclei, wild type and mutant transcripts containing the first intron of the pea rbcS3A gene were expressed in vivo by using an autonomously replicating plant expression vector. Mutations within the normal 5' splice site (+1) of this intron demonstrate that 5' splice sites at the normal exon-intron boundary having only limited agreement with a 5' splice site consensus sequence can be spliced quite effectively in dicot nuclei. Inactivation of the normal 5' splice site occurs only by point mutations of the G at position +1 of the intron (+1G) or +2U or by multiple mutations at other positions and results in the activation of three cryptic 5' splice sites in the adjacent exon and intron. cis competition of cryptic sites having consensus 5' splice site sequences with the normal 5' splice site demonstrates that cryptic splice sites in the exon, but not the intron, can compete to some extent with the normal site. Replacement of the sequences between the cryptic and normal 5' splice sites with heterologous exon or intron sequences demonstrates that the 5' boundary of this plant intron is defined by its position relative to the AU transition point between exon and intron. These results suggest that potential 5' splice sites upstream of the AU transition point are accessible for recognition by the plant pre-mRNA splicing machinery and that those downstream in the AU-rich intron are masked from recognition. PMID- 8441379 TI - The human prointerleukin 1 beta gene requires DNA sequences both proximal and distal to the transcription start site for tissue-specific induction. AB - In these studies, we have identified DNA sequences and specific protein interactions necessary for transcriptional regulation of the human prointerleukin 1 beta (proIL-1 beta) gene. A cell-type-independent lipopolysaccharide (LPS) responsive enhancer element located between -3757 and -2729 bp upstream from the transcription start site (cap site) consisted of at least six discrete subregions which were essential to the maximal induction by LPS in transfected monocytes. The enhancer also appeared to mediate phorbol myristate acetate induction in monocytes and IL-1 responsiveness in fibroblasts. Deletion and base substitution mutations along with DNA binding studies demonstrated that the enhancer contained a minimum of three functional protein binding sequences, two of which appeared to be important for gene induction. One of the essential proteins which bound to the enhancer was similar or identical to members of the C/EBP family of transcription factors required for both IL-1- and LPS-specific induction of the IL-6 gene (i.e., the NF-IL6 proteins). When ligated to the proIL-1 beta cap site-proximal region (located between -131 to +12), both the proIL-1 beta and the simian virus 40 enhancer elements functioned more efficiently in monocytes than in HeLa cells, which are not normally competent for IL-1 beta expression. When ligated to the murine c-fos promoter, however, the proIL-1 beta enhancer was inducible in phorbol myristate acetate-stimulated HeLa cells, suggesting the existence of a proIL-1 beta promoter-proximal requirement for tissue specificity. PMID- 8441380 TI - Influence of guanine nucleotides on complex formation between Ras and CDC25 proteins. AB - The Saccharomyces cerevisiae CDC25 gene and closely homologous genes in other eukaryotes encode guanine nucleotide exchange factors for Ras proteins. We have determined the minimal region of the budding yeast CDC25 gene capable of activity in vivo. The region required for full biological activity is approximately 450 residues and contains two segments homologous to other proteins: one found in both Ras-specific exchange factors and the more distant Bud5 and Lte1 proteins, and a smaller segment of 48 amino acids found only in the Ras-specific exchange factors. When expressed in Escherichia coli as a fusion protein, this region of CDC25 was found to be a potent catalyst of GDP-GTP exchange on yeast Ras2 as well as human p21H-ras but inactive in promoting exchange on the Ras-related proteins Ypt1 and Rsr1. The CDC25 fusion protein catalyzed replacement of GDP-bound to Ras2 with GTP (activation) more efficiently than that of the reverse reaction of replacement of GTP for GDP (deactivation), consistent with prior genetic analysis of CDC25 which indicated a positive role in the activation of Ras. To more directly study the physical interaction of CDC25 and Ras proteins, we developed a protein-protein binding assay. We determined that CDC25 binds tightly to Ras2 protein only in the absence of guanine nucleotides. This higher affinity of CDC25 for the nucleotide-free form than for either the GDP- or GTP-bound form suggests that CDC25 catalyzes exchange of guanine nucleotides bound to Ras proteins by stabilization of the transitory nucleotide-free state. PMID- 8441382 TI - The ubc-2 gene of Caenorhabditis elegans encodes a ubiquitin-conjugating enzyme involved in selective protein degradation. AB - The ubiquitin-protein conjugation system is involved in a variety of eukaryotic cell functions, including the degradation of abnormal and short-lived proteins, chromatin structure, cell cycle progression, and DNA repair. The ubiquitination of target proteins is catalyzed by a ubiquitin-activating enzyme (E1) and ubiquitin-conjugating enzymes (E2s) and in some cases also requires auxiliary substrate recognition proteins (E3s). Multiple E2s have been found, and these likely possess specificity for different classes of target proteins. Here we report the cloning and characterization of a gene (ubc-2) encoding a ubiquitin conjugating enzyme which is involved in the selective degradation of abnormal and short-lived proteins in the nematode Caenorhabditis elegans. The nematode ubc-2 gene encodes a 16.7-kDa protein with striking amino acid sequence similarity to Saccharomyces cerevisiae UBC4 and UBC5 and Drosophila UbcD1. When driven by the UBC4 promoter, ubc-2 can functionally substitute for UBC4 in yeast cells; it rescues the slow-growth phenotype of ubc4 ubc5 mutants at normal temperature and restores their ability to grow at elevated temperatures. Western blots (immunoblots) of ubc4 ubc5 yeast cells transformed with ubc-2 reveal a protein of the expected size, which cross-reacts with anti-Drosophila UbcD1 antibody. C. elegans ubc-2 is constitutively expressed at all life cycle stages and, unlike yeast UBC4 and UBC5, is not induced by heat shock. Both trans and cis splicing are involved in the maturation of the ubc-2 transcript. These data suggest that yeast UBC4 and UBC5, Drosophila UbcD1, and C. elegans ubc-2 define a highly conserved gene family which plays fundamental roles in all eukaryotic cells. PMID- 8441381 TI - V(D)J recombination: signal and coding joint resolution are uncoupled and depend on parallel synapsis of the sites. AB - V(D)J recombination in lymphoid cells is a site-specific process in which the activity of the recombinase enzyme is targeted to signal sequences flanking the coding elements of antigen receptor genes. The order of the steps in this reaction and their mechanistic interdependence are important to the understanding of how the reaction fails and thereby contributes to genomic instability in lymphoid cells. The products of the normal reaction are recombinant joints linking the coding sequences of the receptor genes and, reciprocally, the signal ends. Extrachromosomal substrate molecules were modified to inhibit the physical synapsis of the recombination signals. In this way, it has been possible to assess how inhibiting the formation of one joint affects the resolution efficiency of the other. Our results indicate that signal joint and coding joint formation are resolved independently in that they can be uncoupled from each other. We also find that signal synapsis is critical for the generation of recombinant products, which greatly restricts the degree of potential single-site cutting that might otherwise occur in the genome. Finally, inversion substrates manifest synaptic inhibition at much longer distances than do deletion substrates, suggesting that a parallel rather than an antiparallel alignment of the signals is required during synapsis. These observations are important for understanding the interaction of V(D)J signals with the recombinase. Moreover, the role of signal synapsis in regulating recombinase activity has significant implications for genome stability regarding the frequency of recombinase-mediated chromosomal translocations. PMID- 8441383 TI - Isolation and characterization of DNA sequences that are specifically bound by wild-type p53 protein. AB - Wild-type p53 was shown to function as a transcription factor. The N-terminal region of the protein contains the transcription activation domain, while the C terminus is responsible for DNA binding. Localization of the DNA-binding domain of the p53 protein to the highly conserved carboxy-terminal region suggests that the interaction of p53 with DNA is important for its function. We have developed a strategy for studying the DNA sequence specificity of p53-DNA binding that is based on random sequence selection. We report here on the isolation of murine genomic DNA clones that are specifically bound by the wild-type p53 protein but are not bound by mutant p53 protein forms. The isolated p53 target gene contains the unique DNA-binding sequence GACACTGGTCACACTTGGCTGCTTAGGAAT. This fragment exhibits promoter activity as measured by its capacity to activate transcription of the chloramphenicol acetyltransferase reporter gene. Our results suggest that p53 directly binds DNA and functions as a typical transcription factor. PMID- 8441384 TI - cDNA cloning of transcription factor E4TF1 subunits with Ets and notch motifs. AB - E4TF1 was originally identified as one of the transcription factors responsible for adenovirus E4 gene transcription. It is composed of two subunits, a DNA binding protein with a molecular mass of 60 kDa and a 53-kDa transcription activating protein. Heterodimerization of these two subunits is essential for the protein to function as a transcription factor. In this study, we identified a new E4TF1 subunit, designated E4TF1-47, which has no DNA binding activity but can associate with E4TF1-60. We then cloned the cDNAs for each of the E4TF1 subunits. E4TF1 was purified, and the partial amino acid sequence of each subunit was determined. The predicted amino acid sequence of each cDNA clone revealed that E4TF1-60 had an ETS domain, which is a DNA binding domain common to ets-related transcription factors. E4TF1-53 had four tandemly repeated notch-ankyrin motifs. The putative cDNA of E4TF1-47 coded almost the same amino acid sequences as E4TF1 53. Three hundred and thirty-two amino acids of the N termini of E4TF1-47 and -53 were identical except for one amino acid insertion in E4TF1-53, and they differ from each other at the C terminus. These three recombinant cDNA clones were expressed in Escherichia coli, and the proteins behaved in the same manner as purified proteins in a gel retardation assay. Nucleotide and predicted amino acid sequences were highly homologous to GABP-alpha and -beta, which is further supported by the observation that GABP-specific antibody can recognize human E4TF1. PMID- 8441385 TI - Activation of heat shock gene transcription by heat shock factor 1 involves oligomerization, acquisition of DNA-binding activity, and nuclear localization and can occur in the absence of stress. AB - The existence of multiple heat shock factor (HSF) genes in higher eukaryotes has promoted questions regarding the functions of these HSF family members, especially with respect to the stress response. To address these questions, we have used polyclonal antisera raised against mouse HSF1 and HSF2 to examine the biochemical, physical, and functional properties of these two factors in unstressed and heat-shocked mouse and human cells. We have identified HSF1 as the mediator of stress-induced heat shock gene transcription. HSF1 displays stress induced DNA-binding activity, oligomerization, and nuclear localization, while HSF2 does not. Also, HSF1 undergoes phosphorylation in cells exposed to heat or cadmium sulfate but not in cells treated with the amino acid analog L-azetidine-2 carboxylic acid, indicating that phosphorylation of HSF1 is not essential for its activation. Interestingly, HSF1 and HSF2 overexpressed in transfected 3T3 cells both display constitutive DNA-binding activity, oligomerization, and transcriptional activity. These results demonstrate that HSF1 can be activated in the absence of physiological stress and also provide support for a model of regulation of HSF1 and HSF2 activity by a titratable negative regulatory factor. PMID- 8441386 TI - Regulated splicing of the Drosophila sex-lethal male exon involves a blockage mechanism. AB - In Drosophila melanogaster, sex determination in somatic cells is controlled by a cascade of genes whose expression is regulated by alternative splicing [B. S. Baker, Nature (London) 340:521-524, 1989; J. Hodgkin, Cell 56:905-906, 1989]. The master switch gene in this hierarchy is Sex-lethal. Sex-lethal is turned on only in females, and an autoregulatory feedback loop which controls alternative splicing maintains this state (L. R. Bell, J. I. Horabin, P. Schedl, and T. W. Cline, Cell 65:229-239, 1991; L. N. Keyes, T. W. Cline, and P. Schedl, Cell 68:933-943, 1992). Sex-lethal also promotes female differentiation by controlling the splicing of RNA from the next gene in the hierarchy, transformer. Sosnowski et al. (B. A. Sosnowski, J. M. Belote, and M. McKeown, Cell 58:449-459, 1989) have shown that the mechanism for generating female transformer transcripts is not through the activation of the alternative splice site but by the blockage of the default splice site. We have tested whether an activation or a blockage mechanism is involved in Sex-lethal autoregulation. The male exon of Sex-lethal with flanking splice sites was placed into the introns of heterologous genes. Our results support the blockage mechanism. The poly(U) run at the male exon 3' splice site is required for sex-specific splicing. However, unlike transformer, default splicing to the male exon is sensitive to the sequence context within which the exon resides. This and the observation that the splice signals at the exon are suboptimal are discussed with regard to alternate splicing. PMID- 8441388 TI - Identification of a pentanucleotide telomeric sequence, (TTAGG)n, in the silkworm Bombyx mori and in other insects. AB - A pentanucleotide repetitive sequence, (TTAGG)n, has been isolated from a silkworm genomic library, using cross-hybridization with a (TTNGGG)5 sequence, which is conserved among most eukaryotic telomeres. Both fluorescent in situ hybridization and Bal 31 exonuclease experiments revealed major clusters of (TTAGG)n at the telomeres of all Bombyx chromosomes. To determine the evolutionary origin of this sequence, two types of telomeric sequence, (TTAGG)5 and a hexanucleotide repetitive sequence, (TTAGGG)4, which is conserved mainly among vertebrate and several invertebrate telomeres so far examined, were hybridized to DNAs from a wide variety of eukaryotic species under highly stringent hybridization conditions. The (TTAGGG)5 oligonucleotide hybridized to genomic DNAs from vertebrates and several nonvertebrate species, as has been reported so far, but not to any DNAs from insects. On the other hand, the Bombyx type of telomere sequence, (TTAGG)n, hybridized to DNAs from 8 of 11 orders of insect species tested but not to vertebrate DNAs, suggesting that this TTAGG repetitive sequence is conserved widely among insects. PMID- 8441387 TI - p53-mediated cell death: relationship to cell cycle control. AB - M1 clone S6 myeloid leukemic cells do not express detectable p53 protein. When stably transfected with a temperature-sensitive mutant of p53, these cells undergo rapid cell death upon induction of wild-type (wt) p53 activity at the permissive temperature. This process has features of apoptosis. In a number of other cell systems, wt p53 activation has been shown to induce a growth arrest. Yet, wt 53 fails to induce a measurable growth arrest in M1 cells, and cell cycle progression proceeds while viability is being lost. There exists, however, a relationship between the cell cycle and p53-mediated death, and cells in G1 appear to be preferentially susceptible to the death-inducing activity of wt p53. In addition, p53-mediated M1 cell death can be inhibited by interleukin-6. The effect of the cytokine is specific to p53-mediated death, since apoptosis elicited by serum deprivation is refractory to interleukin-6. Our data imply that p53-mediated cell death is not dependent on the induction of a growth arrest but rather may result from mutually incompatible growth-regulatory signals. PMID- 8441389 TI - Reconstituted human granulocyte-macrophage colony-stimulating factor receptor transduces growth-promoting signals in mouse NIH 3T3 cells: comparison with signalling in BA/F3 pro-B cells. AB - Granulocyte-macrophage colony-stimulating factor (GM-CSF) plays a critical role in growth and differentiation of myeloid cells. We previously reconstituted high affinity human GM-CSF receptor (hGM-CSFR) in a pro-B cell line, BA/F3, by cotransfecting alpha- and beta-chain cDNA clones and showed that the reconstituted receptor could transduce growth-promoting signals. The high affinity hGM-CSFR was also reconstituted in mouse NIH 3T3 cells, but its ability to transduce signals in fibroblasts remained undetermined. In the present study, we further characterized signal transduction by the reconstituted hGM-CSFR in both NIH 3T3 cells and BA/F3 cells. We found that the reconstituted hGM-CSFR transduces signals in NIH 3T3 fibroblasts and BA/F3 cells in response to hGM-CSF to activate transcription of the c-fos, c-jun, and c-myc proto-oncogenes. hGM-CSF also induces protein tyrosine phosphorylation and DNA synthesis in both cell types. These results indicated that hGM-CSFR is functional in fibroblasts, that signal transduction via hGM-CSFR in fibroblasts involves tyrosine kinase(s), and that association of hGM-CSFR with a factor(s) specific to hematopoietic cell lineage is not essential to transduce growth-promoting signals. PMID- 8441390 TI - Growth suppression of Friend virus-transformed erythroleukemia cells by p53 protein is accompanied by hemoglobin production and is sensitive to erythropoietin. AB - The murine allele temperature-sensitive (ts) p53Val-135 encodes a ts p53 protein that behaves as a mutant polypeptide at 37 degrees C and as a wild-type polypeptide at 32 degrees C. This ts allele was introduced into the p53 nonproducer Friend erythroleukemia cell line DP16-1. The DP16-1 cell line was derived from the spleen cells of a mouse infected with the polycythemia strain of Friend virus, and like other erythroleukemia cell lines transformed by this virus, it grows independently of erythropoietin, likely because of expression of the viral gp55 protein which binds to and activates the erythropoietin receptor. When incubated at 32 degrees C, DP16-1 cells expressing ts p53Val-135 protein, arrested in the G0/G1 phase of the cell cycle, rapidly lost viability and expressed hemoglobin, a marker of erythroid differentiation. Erythropoietin had a striking effect on p53Val-135-expressing cells at 32 degrees C by prolonging their survival and diminishing the extent of hemoglobin production. This response to erythropoietin was not accompanied by down-regulation of viral gp55 protein. PMID- 8441391 TI - p21ras and protein kinase C function in distinct and interdependent signaling pathways in C3H 10T1/2 fibroblasts. AB - Both p21ras and protein kinase C (PKC) are believed to function downstream of plasma membrane-associated tyrosine kinases in cellular signal transduction pathways. However, it has remained controversial whether they function in the same pathway and, if so, what their relative position and functional relationship in such a pathway are. We investigated the possibilities that p21ras and PKC function either upstream or downstream of each other in a common linear pathway or that they function independently in colinear signal pathways. Either decreased expression of endogenous normal ras in fibroblasts transfected with an inducible antisense ras construct or overexpression of a mutant ras gene reduced the capacity of the phorbol ester tetradecanoyl phorbol acetate to trigger expression of the tetradecanoyl phorbol acetate-responsive and ras-dependent reporter gene osteopontin (OPN). PKC depletion decreased basal OPN mRNA levels, and the overexpression of ras restored OPN expression to the level of non-PKC-depleted cells. We propose a model in which ras and PKC function in distinct and interdependent signaling pathways. PMID- 8441392 TI - A DNA polymerase mutation that suppresses the segregation bias of an ARS plasmid in Saccharomyces cerevisiae. AB - Yeast autonomously replicating sequence (ARS) plasmids exhibit an unusual segregation pattern during mitosis. While the nucleus divides equally into mother and daughter cells, all copies of the ARS plasmid will often remain in the mother cell. A screen was designed to isolate mutations that suppress this segregation bias. A plasmid with a weak ARS (wARS) that displayed an extremely high segregation bias was constructed. When cells were grown under selection for the wARS plasmid, the resulting colonies grew slowly and had abnormal morphology. A spontaneous recessive mutation that restored normal colony morphology was identified. This mutation suppressed plasmid segregation bias, as indicated by the increased stability of the wARS plasmid in the mutant cells even though the plasmid was present at a lower copy number. An ARS1 plasmid was also more stable in mutant cells than in wild-type cells. The wild-type allele for this mutant gene was cloned and identified as POL delta (CDC2). This gene encodes DNA polymerase delta, which is essential for DNA replication. These results indicate that DNA polymerase delta plays some role in causing the segregation bias of ARS plasmids. PMID- 8441393 TI - Hibernation-associated gene regulation of plasma proteins with a collagen-like domain in mammalian hibernators. AB - In mammals, hibernation is expressed by only a limited number of species, and the molecular mechanisms underlying hibernation are not well understood. Recently, we have found plasma proteins which disappear from blood specifically during hibernation in a mammalian hibernator, the chipmunk. Here, we report the cDNA cloning of these chipmunk hibernation-related proteins, HP-20, -25, and -27, and analyses of their expression. All three proteins contain a collagen-like domain near the N terminus and are highly homologous to each other. Their mRNAs were detected only in liver in nonhibernating chipmunks, and in hibernating chipmunks, the amounts were reduced to less than 1/10 of those in nonhibernating chipmunks, indicating that HP-20, -25, and -27 mRNA expression is regulated similarly in association with hibernation. Southern blot analyses of the squirrel family with each of chipmunk HP-20, -25, and -27 cDNA revealed that a nonhibernating species (tree squirrel) as well as another hibernating species (ground squirrel) retained the corresponding genes. However, their transcripts were detected only with the hibernating species, and in hibernating ground squirrels, their levels were greatly reduced compared with those in nonhibernating animals, as were the cases with the chipmunk. These observations are the first line of evidence for occurrence of hibernation-associated gene regulation. The results would indicate the commitment of HP-20, -25, and -27 to hibernation and support the idea that genetic controls are involved in mammalian hibernation. PMID- 8441394 TI - Phosphatidylcholine hydrolysis and c-myc expression are in collaborating mitogenic pathways activated by colony-stimulating factor 1. AB - Stimulation of diglyceride production via phospholipase C (PLC) hydrolysis of phosphatidylcholine was an early event in the mitogenic action of colony stimulating factor 1 (CSF-1) in the murine macrophage cell line BAC1.2F5 and was followed by a second phase of diglyceride production that persisted throughout the G1 phase of the cell cycle. Addition of phosphatidylcholine-specific PLC (PC PLC) from Bacillus cereus to the medium of quiescent cells raised the intracellular diglyceride concentration and stimulated [3H]thymidine incorporation, although PC-PLC did not support continuous proliferation. PC-PLC treatment did not induce tyrosine phosphorylation or turnover of the CSF-1 receptor. The major protein kinase C (PKC) isotype in BAC1.2F5 cells was PKC delta. Diglyceride production from PC-PLC did not target PKC-delta, since unlike phorbol esters, PC-PLC treatment neither decreased the electrophoretic mobility of PKC-delta nor increased the amount of GTP bound to Ras, and PC-PLC was mitogenically active in BAC1.2F5 cells in which PKC-delta was downregulated by prolonged treatment with phorbol ester. PC-PLC mimicked CSF-1 action by elevating c-fos and junB mRNAs to 40% of the level induced by CSF-1; however, PC-PLC induced c-myc mRNA to only 5% of the level in CSF-1-stimulated cells. PC-PLC addition to CSF-1-dependent BAC1.2F5 clones that constitutively express c-myc increased [3H]thymidine incorporation to 86% of the level evoked by CSF-1 and supported slow growth in the absence of CSF-1. Therefore, PC-PLC is a component of a signal transduction pathway leading to transcription of c-fos and junB that collaborates with c-myc and is independent of PKC-delta and Ras activation. PMID- 8441395 TI - The mechanism by which the human apolipoprotein B gene reducer operates involves blocking of transcriptional activation by hepatocyte nuclear factor 3. AB - Previously, we showed that when a DNA fragment extending from -3067 to -2734 of the human apolipoprotein B (apo-B) gene is inserted immediately upstream of an apo-B promoter segment (-139 to +121), transcription from this promoter is reduced by about 10-fold in cultured colon carcinoma cells (CaCo-2) but not in cultured hepatoma cells (HepG2). We postulated that this reducer operates by a mechanism involving active repression of a transcriptional activator that binds to the segment from -111 to -88 of the apo-B promoter (B. Paulweber and B. Levy Wilson, J. Biol. Chem. 266:24161-24168 1991). In the current study, the reducer element has been localized to a 24-bp sequence from -2801 to -2778 of the apo-B gene that contains a binding site for the negative regulatory protein ARP-1. Furthermore, we have demonstrated that the transcription factor hepatocyte nuclear factor 3 alpha (HNF-3 alpha) binds to the sequence 5'-TGTTTGCTTTTC-3' from -95 to -106 of the apo-B promoter, to stimulate transcription. Transcriptional activation by HNF-3 is repressed when the reducer sequence is inserted immediately upstream of the HNF-3 binding site, suggesting a mechanism by which the reducer-bound protein blocks the activation promoted by HNF-3. Data from cotransfection experiments in which ARP-1 is overexpressed in the absence of its binding site suggest that ARP-1 interacts either directly or via a mediator protein with proteins recognizing the HNF-3 site and that this interaction is sufficient to repress transcriptional activation by HNF-3. Because transcriptional activation by Sp1 is not affected by the reducer, it is unlikely that the reducer interacts directly with basic components of the transcriptional machinery. PMID- 8441396 TI - The immunoglobulin heavy chain locus contains another B-cell-specific 3' enhancer close to the alpha constant region. AB - The transcription of immunoglobulin genes is controlled by variable region promoters and by enhancers, both of which are lymphoid specific. Because immunoglobulin genes are subject to an extremely complex regulation, we anticipated that there might be additional control elements for these genes. We therefore sought additional enhancers and demonstrate here that there is indeed another weak transcriptional enhancer just 3' to the mouse alpha constant region. This novel immunoglobulin enhancer is lymphoid specific and at two positions can bind members of the Oct family of transcription factors. PMID- 8441397 TI - Nonimmune thyroid destruction results from transgenic overexpression of an allogeneic major histocompatibility complex class I protein. AB - The overexpression of major histocompatibility complex (MHC) class I molecules in endocrine epithelial cells is an early feature of autoimmune thyroid disease and insulin-dependent diabetes mellitus, which may reflect a cellular response, e.g., to viruses or toxins. Evidence from a transgenic model in pancreatic beta cells suggests that MHC class I overexpression could play an independent role in endocrine cell destruction. We demonstrate in this study that the transgenic overexpression of an allogeneic MHC class I protein (H-2Kb) linked to the rat thyroglobulin promoter, in H-2Kk mice homozygous for the transgene, leads to thyrocyte atrophy, hypothyroidism, growth retardation, and death. Thyrocyte atrophy occurred in the absence of lymphocytic infiltration. Tolerance to allogeneic class I was revealed by the reduced ability of primed lymphocytes from transgenic mice to lyse H-2Kb target cells in vitro. This nonimmune form of thyrocyte destruction and hypothyroidism recapitulates the beta-cell destruction and diabetes that results from transgenic overexpression of MHC class I molecules in pancreatic beta cells. Thus, we conclude that overexpression of MHC class I molecules may be a general mechanism that directly impairs endocrine epithelial cell viability. PMID- 8441399 TI - Complex telomere-associated repeat units in members of the genus Chironomus evolve from sequences similar to simple telomeric repeats. AB - The dipteran Chironomus tentans has complex tandemly repeated 350-bp DNA sequences at or near the chromosome ends. As in Drosophila melanogaster, short simple repeats with cytosines and guanines in different strands have never been observed. We were therefore interested in learning whether the Chironomus repeats could have evolved from simple sequence telomeric DNA, which might suggest that they constitute a functional equivalent. We screened for repeat units with evolutionarily ancient features within the tandem arrays and recovered two clones with a less-evolved structure. Sequence analysis reveals that the present-day 350 bp unit probably evolved from a simpler 165-bp unit through the acquisition of transposed sequences. The 165-bp unit contains DNA with a highly biased distribution of cytosine and guanine between the two strands, although with the ratios inverted in two minor parts of the repeat. It is largely built up of short degenerate subrepeats for which most of the sequence can be reconstructed. The consensus for the subrepeat sequence is similar to the simple telomeric repeat sequences of several kinds of eukaryotes. We propose that the present-day unit has evolved from telomeric, simple sequence, asymmetric DNA from which it has retained some original sequence features and possibly functions. PMID- 8441398 TI - Both N- and C-terminal domains of RelB are required for full transactivation: role of the N-terminal leucine zipper-like motif. AB - RelB, a member of the Rel family of transcription factors, can stimulate promoter activity in the presence of p50-NF-kappa B or p50B/p49-NF-kappa B in mammalian cells. Transcriptional activation analysis reveals that the N and C termini of RelB are required for full transactivation in the presence of p50-NF-kappa B. RelB/p50-NF-kappa B hybrid molecules containing the Rel homology domain of p50-NF kappa B and the N and C termini of RelB have high transcriptional activity compared with wild-type p50-NF-kappa B. The N and C termini of RelB cooperate in transactivation in cis or trans configuration. Alterations in the structure of the leucine zipper-like motif present in the N terminus of RelB significantly decrease the transcriptional capacity of RelB and of different RelB/p50-NF-kappa B hybrid molecules. PMID- 8441400 TI - Wnt-1-inducing factor-1: a novel G/C box-binding transcription factor regulating the expression of Wnt-1 during neuroectodermal differentiation. AB - The Wnt-1 proto-oncogene is essential for proper development of the midbrain and is expressed in a spatially and temporally restricted manner during central nervous system development in mice. In vitro, the gene is specifically transcribed during the retinoic acid (RA)-induced neuroectodermal differentiation of the P19 line of embryonal carcinoma cells. The P19 cells differentiate into neurons, astrocytes, and fibroblast-like cells when treated with RA. Treatment of the cells with dimethyl sulfoxide leads to differentiation along mesodermal lineages, including skeletal and cardiac muscle. We have used the P19 cell line to study the Wnt-1 promoter and identify and characterize the transcription factor(s) that regulates the differentiation-specific transcription of Wnt-1 in RA-treated P19 cultures. Transient-transfection assays have revealed that a 230 bp region comprising positions -278 to -47 of the 5' upstream Wnt-1 sequence was sufficient to direct RA-specific transcription. This promoter fragment was shown to contain a binding site for a nuclear factor that was not detected in undifferentiated P19 stem cells or their dimethyl sulfoxide-treated derivatives but was induced in differentiating RA-treated cells. This factor was termed Wnt-1 inducing factor-1 (WiF-1). DNase I footprinting analysis has identified the G/C rich WiF-1 binding site, and UV cross-linking studies have shown that WiF-1 is a protein with an M(r) of 65,000. WiF-1 binding activity was also detected in postpubertal mouse testis, the only tissue that expresses Wnt-1 in adults. Site directed mutations that inhibited WiF-1 binding to the Wnt-1 promoter concomitantly abolished the activity of the promoter in RA-treated P19 cells. The active WiF-1 protein was purified by DNA affinity chromatography. Our data suggest that WiF-1 is a novel G/C box-binding transcription factor and support a physiological role for WiF-1 in the developmentally regulated expression of Wnt 1. PMID- 8441401 TI - A protein synthesis-dependent increase in E2F1 mRNA correlates with growth regulation of the dihydrofolate reductase promoter. AB - Enhanced expression of genes involved in nucleotide biosynthesis, such as dihydrofolate reductase (DHFR), is a hallmark of entrance into the DNA synthesis (S) phase of the mammalian cell cycle. To investigate the regulated expression of the DHFR gene, we stimulated serum-starved NIH 3T3 cells to synchronously reenter the cell cycle. Our previous results show that a cis-acting element at the site of DHFR transcription initiation is necessary for serum regulation. Recently, this element has been demonstrated to bind the cloned transcription factor E2F. In this study, we focused on the role of E2F in the growth regulation of DHFR. We demonstrated that a single E2F site, in the absence or presence of other promoter elements, was sufficient for growth-regulated promoter activity. Next, we showed that the increase in DHFR mRNA at the G1/S-phase boundary required protein synthesis, raising the possibility that a protein(s) lacking in serum-starved cells is required for DHFR transcription. We found that, similar to DHFR mRNA expression, levels of murine E2F1 mRNA were low in serum-starved cells and increased at the G1/S-phase boundary in a protein synthesis-dependent manner. Furthermore, in a cotransfection experiment, expression of human E2F1 stimulated the DHFR promoter 22-fold in serum-starved cells. We suggest that E2F1 may be the key protein required for DHFR transcription that is absent in serum-starved cells. Expression of E2F also abolished the serum-stimulated regulation of the DHFR promoter and resulted in transcription patterns similar to those seen with expression of the adenoviral oncoprotein E1A. In summary, we provide evidence for the importance of E2F in the growth regulation of DHFR and suggest that alterations in the levels of E2F may have severe consequences in the control of cellular proliferation. PMID- 8441402 TI - Mammalian U6 small nuclear RNA undergoes 3' end modifications within the spliceosome. AB - Mammalian U6 small nuclear RNA (snRNA) is heterogeneous with respect to the number of 3' terminal U residues. The major form terminates with five U residues and a 2',3' cyclic phosphate. Because of the presence in HeLa cell nuclear extracts of a terminal uridylyl transferase, a minor form of U6 snRNA is elongated, producing multiple species containing up to 12 U residues. In this study we have used glycerol gradients to demonstrate that these U6 snRNA forms are assembled into U6 ribonucleoprotein (RNP), U4/U6 snRNPs, and U4/U5/U6 tri snRNP complexes. Furthermore, glycerol gradients combined with affinity selection of biotinylated pre-mRNAs led us to show that elongated forms of U6 snRNAs enter the spliceosome and that some of these become shortened with time to a single species having the same characteristics as the major form of U6 snRNA present in mammalian nuclear extracts. We propose that this elongation-shortening process is related to the function of U6 snRNA in mammalian pre-mRNA splicing. PMID- 8441403 TI - Differential effects of expression of the CD45 tyrosine protein phosphatase on the tyrosine phosphorylation of the lck, fyn, and c-src tyrosine protein kinases. AB - Expression of the CD45 tyrosine protein phosphatase is required for the response of functional lymphocytes to stimulation through the antigen receptor. One or more of its substrates may therefore be essential for signal transduction during lymphocyte activation. We have studied the phosphorylation of the closely related lck, fyn, and c-src tyrosine protein kinases in leukemic murine T-cell lines that have lost the expression of CD45. The phosphorylation of the lck kinase at an inhibitory site of tyrosine phosphorylation, Tyr-505, was increased by two-, six , and eightfold in three different cell lines. Phosphorylation of the fyn kinase at the homologous site, Tyr-531, was unaltered in one of these cell lines, but increased by 2.5-fold in the two others. The phosphorylation of p60c-src at the homologous tyrosine was essentially unchanged in the one CD45-negative cell line in which it was examined. The expression of CD45 therefore regulates the phosphorylation and potentially the activity of the lck and fyn tyrosine protein kinases, but the effect on the lck kinase is much greater than on the fyn kinase. This finding and the observation that CD45 had no effect on the phosphorylation of p60c-src suggest that CD45 exhibits polypeptide substrate specificity in vivo. Additionally, these findings are consistent with the hypothesis that the unresponsiveness of CD45-negative lymphoid cells to antigenic stimulation is due largely to hyperphosphorylation of the lck kinase. PMID- 8441405 TI - Mechanisms of p34cdc2 regulation. AB - The kinase activity of human p34cdc2 is negatively regulated by phosphorylation at Thr-14 and Tyr-15. These residues lie within the putative nucleotide binding domain of p34cdc2. It has been proposed that phosphorylation within this motif ablates the binding of ATP to the active site of p34cdc2, thereby inhibiting p34cdc2 kinase activity (K. Gould and P. Nurse, Nature [London] 342:39-44, 1989). To understand the mechanism of this inactivation, various forms of p34cdc2 were tested for the ability to bind nucleotide. The active site of p34cdc2 was specifically modified by the MgATP analog 5'-p-fluorosulfonylbenzoyladenosine (FSBA). The apparent Km for modification of wild-type, monomeric p34cdc2 was 148 microM FSBA and was not significantly affected by association with cyclin B. Tyrosine-phosphorylated p34cdc2 was modified by FSBA with a slightly higher Km (241 microM FSBA). FSBA modification of both tyrosine-phosphorylated and unphosphorylated p34cdc2 was competitively inhibited by ATP, and half-maximal inhibition in each case occurred at approximately 250 microM ATP. In addition to being negatively regulated by phosphorylation, the kinase activity of p34cdc2 was positively regulated by the cyclin-dependent phosphorylation of Thr-161. Mutation of p34cdc2 at Thr-161 resulted in the formation of an enzymatically inactive p34cdc2/cyclin B complex both in vivo and in vitro. However, mutation of Thr-161 did not significantly affect the ability of p34cdc2 to bind nucleotide (FSBA). Taken together, these results indicate that inhibition of p34cdc2 kinase activity by phosphorylation of Tyr-15 (within the putative ATP binding domain) or by mutation of Thr-161 involves a mechanism other than inhibition of nucleotide binding. We propose instead that the defect resides at the level of catalysis. PMID- 8441404 TI - Conservation of transcriptional activation functions of the NF-kappa B p50 and p65 subunits in mammalian cells and Saccharomyces cerevisiae. AB - The NF-kappa B transcription factor complex is composed of a 50-kDa (p50) and a 65-kDa (p65) subunit. Both subunits bind to similar DNA motifs and elicit transcriptional activation as either homo- or heterodimers. By using chimeric proteins that contain the DNA binding domain of the yeast transcriptional activator GAL4 and subdomains of p65, three distinct transcriptional activation domains were identified. One domain was localized to a region of 42 amino acids containing a potential leucin zipper structure, consistent with earlier reports. Two other domains, both acidic and rich in prolines, were also identified. Of perhaps more significance, the same minimal activation domains that were functional in mammalian cells were also functional in the yeast Saccharomyces cerevisiae. Coexpression of the NF-kappa B inhibitory molecule, I kappa B, reduced the transcriptional activity of p65 significantly, suggesting the ability of I kappa B to function in a similar manner in S. cerevisiae. Surprisingly, while the conserved rel homology domain of p65 demonstrated no transcriptional activity in either mammalian cells or S. cerevisiae, the corresponding domain in p50 was a strong transcriptional activator in S. cerevisiae. The observation that similar domains elicit transcriptional activation in mammalian cells and S. cerevisiae demonstrates strong conservation of the transcriptional machinery required for NF-kappa B function and provides a powerful genetic system to study the transcriptional mechanisms of these proteins. PMID- 8441407 TI - Expression of a gene duplication encoding conserved sperm tail proteins is translationally regulated in Drosophila melanogaster. AB - We have analyzed a locus of Drosophila melanogaster located at 98C on chromosome 3, which contains two tandemly arranged genes, named Mst98Ca and Mst98Cb. They are two additional members of the Mst(3)CGP gene family by three criteria. (i) Both genes are exclusively transcribed in the male germ line. (ii) Both transcripts encode a protein with a high proportion of the repetitive motif Cys Gly-Pro. (iii) Their expression is translationally controlled; while transcripts can be detected in diploid stages of spermatogenesis, association with polysomes can be shown only in haploid stages of sperm development. The genes differ markedly from the other members of the gene family in structure; they do not contain introns, they are of much larger size, and they have the Cys-Gly-Pro motifs clustered at the carboxy-terminal end of the encoded proteins. An antibody generated against the Mst98Ca protein recognizes both Mst98C proteins in D. melanogaster. In a male-sterile mutation in which spermiogenesis is blocked before individualization of sperm, both of these proteins are no longer synthesized. This finding provides proof of late translation for the Mst98C proteins and thereby independent proof of translational control of expression. Northern (RNA) and Western immunoblot analyses indicate the presence of homologous gene families in many other Drosophila species. The Mst98C proteins share sequence homology with proteins of the outer dense fibers in mammalian spermatozoa and can be localized to the sperm tail by immunofluorescence with an anti-Mst98Ca antibody. PMID- 8441406 TI - T cell receptor-beta mRNA splicing: regulation of unusual splicing intermediates. AB - The expression of functional T cell receptor-beta (TCR-beta) transcripts requires the activation of programmed DNA rearrangement events. It is not clear whether other mechanisms dictate TCR-beta mRNA levels during thymic ontogeny. We examined the potential role of RNA splicing as a regulatory mechanism. As a model system, we used an immature T cell clone, SL12.4, that transcribes a fully rearranged TCR beta gene but essentially lacks mature 1.3-kb TCR-beta transcripts in the cytoplasm. Abundant TCR-beta splicing intermediates accumulate in the nucleus of this cell clone. These splicing intermediates result from inefficient or inhibited excision of four of the five TCR-beta introns; the only intron that is efficiently spliced is the most 5' intron, IVSL. The focal point for the regulation appears to be IVS1C beta 1 and IVS2C beta 1, since unusual splicing intermediates that have cleaved the 5' splice site but not the 3' splice site of these two introns accumulate in vivo. The block in 3' splice site cleavage is of interest since sequence analysis reveals that these two introns possess canonical splice sites. A repressional mechanism involving a labile repressor protein may be responsible for the inhibition of RNA splicing since treatment of SL12.4 cells with the protein synthesis inhibitor cycloheximide reversibly induces a rapid and dramatic accumulation of fully spliced TCR-beta transcripts in the cytoplasm, concomitant with a decline in TCR-beta pre-mRNAs in the nucleus. This inducible system may be useful for future studies analyzing the underlying molecular mechanisms that regulate RNA splicing. PMID- 8441408 TI - Ligand-dependent, Pit-1/growth hormone factor-1 (GHF-1)-independent transcriptional stimulation of rat growth hormone gene expression by thyroid hormone receptors in vitro. AB - The expression of the rat growth hormone (rGH) gene in the anterior pituitary gland is modulated by Pit-1/GHF-1, a pituitary-specific transcription factor, and by other more widely distributed factors, such as the thyroid hormone receptors (TRs), Sp1, and the glucocorticoid receptor. Thyroid hormone (T3)-mediated transcriptional stimulation of rGH gene expression has been extensively studied in vivo and in vitro including the measurements of (i) rGH mRNA by blot hybridization, (ii) transcriptional rate of rGH gene by nuclear run-on, and (iii) reporter gene expression in which a chimeric plasmid containing 5'-flanking sequences of the rGH gene linked to a reporter gene has been transfected either stably or transiently into pituitary and/or nonpituitary cells. From these studies, it has been suggested that the Pit-1/GHF-1 binding site is necessary for full T3 action. We developed a cell-free in vitro transcription system to examine further the roles of the TRs and Pit-1/GHF-1 in rGH gene activation. Using GH3 nuclear extract as a source of TRs and Pit-1/GHF-1, this in vitro transcription assay showed that T3 stimulation of rGH promoter activity is dependent on the addition of T3 to the GH3 nuclear extract. This transcriptional stimulation was augmented with increasing concentrations of ligand and was T3, but not T4 or reverse T3, specific. T3-mediated stimulation of rGH promoter activity was completely abolished by preincubation of the nuclear extract with rGH-thyroid hormone response element (-200 to -160) but not with Pit-1/GHF-1 (-137 to -65) oligonucleotides. Further, neither deletion of both Pit-1/GHF-1 binding sites nor mutation of the proximal Pit-1/GHF-1 binding site from the rGH promoter abrogated the T3 effect. These results provide evidence that T3-stimulated rGH promoter activity is independent of Pit-1/GHF-1 and raise the possibility that the stimulation of rGH gene expression by T3 might involve direct interaction of TRs with the general transcriptional apparatus. PMID- 8441409 TI - SH1 domain autophosphorylation of P210 BCR/ABL is required for transformation but not growth factor independence. AB - P210 BCR/ABL is a chimeric oncogene implicated in the pathogenesis of chronic myelogenous leukemia. BCR sequences have been shown to be required for activation of the tyrosine kinase and transforming functions of BCR/ABL. In this work, we show that two other structural requirements for full transforming activity of P210 BCR/ABL include a functional tyrosine kinase and the presence of tyrosine 1294, a site of autophosphorylation within the tyrosine kinase domain. Replacement of tyrosine 1294 with phenylalanine (1294F) greatly diminishes the transforming activity of BCR/ABL without affecting the specific activity of the protein tyrosine kinase. Expression of an exogenous myc gene in fibroblasts partially complements the transforming capacity of mutant P210 BCR/ABL (1294F). Surprisingly, tyrosine 1294 is not required for efficient induction of growth factor-independence in hematopoietic cell lines by P210 BCR/ABL. These results suggest that autophosphorylation at tyrosine 1294 may be important for recognition and phosphorylation of cellular substrates in the pathway of transformation, but it is not critical for mediating the events which lead to growth factor independence. PMID- 8441410 TI - Purification and characterization of the stage-specific embryonic enhancer binding protein SSAP-1. AB - We have demonstrated that a highly conserved segment of DNA between positions 288 and -317 (upstream sequence element IV [USE IV]) is largely responsible for the transcriptional activation of the sea urchin H1-beta histone gene during the blastula stage of embryogenesis. This sequence is capable of acting as an embryonic enhancer element, activating target genes in a stage-specific manner. Nuclear extracts prepared from developmentally-staged organisms before and after the gene is activated all contain a factor which specifically binds to the enhancer. We have purified a 43-kDa polypeptide which binds to and footprints the USE IV enhancer element. We refer to this protein as stage-specific activator protein 1 (SSAP-1). Early in development before the enhancer is active, SSAP appears as a 43-kDa monomer, but it undergoes a change in its molecular weight beginning at about 12 h postfertilization (early blastula) which precisely parallels the increase in H1-beta gene expression. Modified SSAP has an apparent molecular mass of approximately 90 to 100 kDa and contains at least one 43-kDa SSAP polypeptide. Thus, it is the disappearance of the 43-kDa species and the appearance of the 90- to 100-kDa species which coincide with the H1-beta gene activation. The correlation between the change in molecular weight of SSAP and the stage-specific activation of H1-beta gene expression strongly suggests that this higher-molecular-weight form of SSAP is directly responsible for the blastula stage-specific transcriptional activation of the late H1 gene. PMID- 8441411 TI - Progression of interleukin-2 (IL-2)-dependent rat T cell lymphoma lines to IL-2 independent growth following activation of a gene (Gfi-1) encoding a novel zinc finger protein. AB - During progression of Moloney murine leukemia virus (Mo-MuLV)-induced rat T cell lymphomas, growth selection results in the expansion of cell clones carrying increasing numbers of integrated proviruses. These new provirus insertions reproducibly contribute to enhanced growth, allowing the emergence of cell clones from the initially heterogeneous population of tumor cells. The Mo-MuLV-induced rat T cell lymphoma lines 2780d and 5675d, which are dependent on interleukin-2 (IL-2) for growth in culture (IL-2d), were placed in IL-2-free medium to select for IL-2-independent (IL-2i) mutants. Southern blot analysis of genomic DNA from these mutants, which was hybridized to a Mo-MuLV long terminal repeat probe, revealed that all mutants carried new provirus insertions (from one to four new proviruses per cell line). A locus of integration identified through cloning of the single new provirus detected in one of the IL-2i mutants, 2780i.5, was found to be the target of provirus insertion in 1 additional IL-2i cell line of 24 tested. A full-length cDNA of a gene (growth factor independence-1 [Gfi-1]) activated by promoter insertion in the 2780i.5 cells was cloned and shown to encode a novel zinc finger protein. Gfi-1 is expressed at low levels in IL-2d cell lines cultured in IL-2-containing medium and at high levels in most IL-2i cell lines, including the two harboring a provirus at this locus. Gfi-1 expression in adult animals is restricted to the thymus, spleen, and testis. In mitogen-stimulated splenocytes, Gfi-1 expression begins to rise at 12 h after stimulation and reaches very high levels after 50 h, suggesting that it may be functionally involved in events occurring after the interaction of IL-2 with its receptor, perhaps during the transition from the G1 to the S phase of the cell cycle. In agreement with this, Gfi-1 does not induce the expression of IL-2. Expression of Gfi-1 in 2780d cells following transfer of a Gfi-1/LXSN retrovirus construct contributes to the emergence of the IL-2i phenotype. PMID- 8441413 TI - A dosage-dependent suppressor of a temperature-sensitive calmodulin mutant encodes a protein related to the fork head family of DNA-binding proteins. AB - The cmd1-1 mutation of calmodulin causes temperature-sensitive growth in Saccharomyces cerevisiae. We have isolated a dosage-dependent suppressor of cmd1 1, designated HCM1. Twentyfold overexpression of HCM1 permits strains carrying cmd1-1 to grow at temperatures up to and including 34 degrees C but does not suppress the lethality of either cmd1-1 at higher temperatures or the deletion of CMD1. Thus, overexpression of HCM1 does not bypass the requirement for calmodulin but enhances the ability of the mutant calmodulin to function. HCM1 is not essential for growth, but deletion of HCM1 exacerbates the phenotype of a strain carrying cmd1-1. HCM1 is located on chromosome III, which was recently sequenced. Our results correct errors in the published DNA sequence. The putative polypeptide encoded by HCM1 is 564 amino acids long and has a predicted molecular weight of 63,622. Antisera prepared against Hcm1p detect a protein that is overproduced in yeast strains overexpressing HCM1 and has an apparent molecular mass of 65 kDa. Eighty-six amino acid residues in the N terminus of Hcm1p show 50% identity with a DNA-binding region of the fork head family of DNA-binding proteins. When fused to the DNA-binding domain of Gal4p, residues 139 to 511 of Hcm1p can act as a strong activator of transcription. However, overexpression of HCM1 does not affect the expression of calmodulin. Furthermore, Hcm1p does not bind to calmodulin in a gel overlay assay. Thus, overexpression of HCM1 enhances calmodulin function by an apparently indirect mechanism. PMID- 8441412 TI - Differential pp40I kappa B-beta inhibition of DNA binding by rel proteins. AB - Regulation of gene expression by members of the NF-kappa B/rel transcription factor family is a central component of signal transduction pathways utilized by many cellular processes, including lymphocyte activation, embryonic development, and oncogenesis. The members of the NF-kappa B/rel transcription factor family are regulated by association with a family of inhibitor (I kappa B) proteins (I kappa B) proteins. To address the importance of the association between rel and I kappa B proteins for oncogenesis by rel proteins, we characterized rel-I kappa B interactions in chicken embryo fibroblasts (CEF) infected with retroviral vectors encoding the avian c-rel (p68c-rel), v-rel (p59v-rel), and I kappa B-beta (pp40I kappa B-beta) proteins. In these experiments, the p59v-rel:pp40I kappa B-beta ratio in coinfected CEF was nearly identical to the p59v-rel:pp40I kappa B-beta ratio in v-rel-transformed cells. The avian I kappa B-beta protein, pp40I kappa B beta, was able to associate with both the nononcogenic p68c-rel and the oncogenic p59v-rel. Association of p68c-rel with pp40I kappa B-beta in coinfected CEF resulted in inhibition of the DNA-binding activity of p68c-rel. Anti-pp40I kappa B-beta serum was able to restore DNA binding to p68c-rel in the presence of high levels of pp40I kappa B-beta, indicating that pp40I kappa B-beta functions in a trans-acting manner to inhibit DNA binding by p68c-rel. In contrast, sequence specific DNA binding by the oncogenic v-rel protein, p59v-rel, was not abolished by pp40I kappa B-beta in coinfected CEF. Anti-pp40I kappa B-beta serum did not immunoprecipitate the p59v-rel-DNA adduct or alter the electrophoretic mobility of the p59v-rel-DNA adduct, consistent with the idea that pp40I kappa B-beta and DNA are competitive inhibitors for the same or overlapping domains on rel proteins. Internal v-rel-derived sequences were identified that are responsible for loss of pp40I kappa B-beta-mediated inhibition of DNA binding by p59v-rel. Loss of pp40I kappa B-beta-mediated inhibition of DNA binding by recombinant v/c rel proteins was not sufficient for oncogenic activation of c-rel. Instead, removal of C-terminal c-rel-derived sequences in addition to loss of pp40I kappa B-beta-mediated inhibition of DNA binding was required for oncogenic activation of c-rel. These results demonstrate the presence of an interaction between internal and C-terminal regions of the c-rel protein that is important for the ability of c-rel to regulate the proliferation of lymphoid cells. PMID- 8441414 TI - Transcriptional repression in Saccharomyces cerevisiae by a SIN3-LexA fusion protein. AB - The yeast SIN3 gene (also known as SDI1, UME4, RPD1, and GAM2) has been identified as a transcriptional regulator. Previous work has led to the suggestion that SIN3 regulates transcription via interactions with DNA-binding proteins. Although the SIN3 protein is located in the nucleus, it does not bind directly to DNA in vitro. We have expressed a LexA-SIN3 fusion protein in Saccharomyces cerevisiae and show that this fusion protein represses transcription from heterologous promoters that contain lexA operators. The predicted amino acid sequence of the SIN3 protein contains four copies of a paired amphipathic helix (PAH) motif, similar to motifs found in HLH (helix-loop helix) and TPR (tetratricopeptide repeat) proteins, and these motifs are proposed to be involved in protein-protein interactions. We have conducted a deletion analysis of the SIN3 gene and show that the PAH motifs are required for SIN3 activity. Additionally, the C-terminal region of the SIN3 protein is sufficient for repression activity in a LexA-SIN3 fusion, and deletion of a PAH motif in this region inactivates this repression activity. A model is presented in which SIN3 recognizes specific DNA-binding proteins in vivo in order to repress transcription. PMID- 8441415 TI - Alpha B-crystallin expression in mouse NIH 3T3 fibroblasts: glucocorticoid responsiveness and involvement in thermal protection. AB - alpha B-crystallin, a major soluble protein of vertebrate eye lenses, is a small heat shock protein which transiently accumulates in response to heat shock and other kinds of stress in mouse NIH 3T3 fibroblasts. Ectopic expression of an alpha B-crystallin cDNA clone renders NIH 3T3 cells thermoresistant. alpha B crystallin accumulates in response to the synthetic glucocorticoid hormone dexamethasone. Dexamethasone-treated NIH 3T3 cells become thermoresistant to the same extent as they accumulate alpha B-crystallin. A cell clone in which alpha B crystallin is superinduced upon heat shock acquires augmented thermotolerance. Expression of the ras oncogene causes a rapid but transient accumulation of alpha B-crystallin within 1 day. Later, sustained ras oncogene expression suppresses the dexamethasone-mediated alpha B-crystallin accumulation. Thus, oncogenic transformation triggered by the ras oncogene interferes with hormone-mediated accumulation of alpha B-crystallin and concomitant acquisition of thermoresistance. Other known heat shock proteins do not accumulate in response to ectopic alpha B-crystallin expression or to dexamethasone treatment. These results indicate that alpha B-crystallin can protect NIH 3T3 fibroblasts from thermal shock. PMID- 8441416 TI - COUP-TF acts as a competitive repressor for estrogen receptor-mediated activation of the mouse lactoferrin gene. AB - We previously demonstrated that the estrogen response module (mERM) of the mouse lactoferrin gene, which contains an overlapping chicken ovalbumin upstream promoter transcription factor (COUP-TF)- and estrogen receptor-binding element, is responsible for estrogen induction. In this report we show that COUP-TF represses the mERM response to estrogen stimulation. Mutation and deletion of the COUP-TF-binding element or reduction of the endogenous COUP-TF increases mERM estrogen responsiveness. Likewise, overexpression of the COUP-TF expression vector blocked the estrogen-stimulated response of mERM in transfected cells. The molecular mechanism of this repression is due to the competition between COUP-TF and the estrogen receptor for binding at identical contact sites in the overlapping region of the mERM. Our results indicate that two members of the steroid-thyroid receptor superfamily work in concert to modulate lactoferrin gene expression. PMID- 8441417 TI - Downregulation of Ke 6, a novel gene encoded within the major histocompatibility complex, in murine polycystic kidney disease. AB - Polycystic kidney disease (PKD) is characterized by progressive enlargement of the kidneys due to numerous expanding cysts ultimately leading to renal failure. We have identified a gene, Ke 6, located within the H-2K/tw5 region on mouse chromosome 17, which is downregulated in two distinct murine models of heritable PKD. Ke 6 is a member of the short-chain alcohol dehydrogenase family and possess remarkable amino acid sequence conservation with several bacterial proteins with oxidoreductase function. The Ke 6 gene gives rise to two transcripts--a 1-kb Ke 6a mRNA which is abundant in kidney and liver tissue and a 1.4-kb Ke 6b mRNA which is found at a moderate level in spleen tissue. We report here the complete nucleotide sequence of Ke 6a cDNA and the expression of the Ke 6 gene in murine models of PKD. The Ke 6 gene may be intimately involved in the manifestation of these cystic kidney diseases. PMID- 8441418 TI - A nuclear factor for interleukin-6 expression (NF-IL6) and the glucocorticoid receptor synergistically activate transcription of the rat alpha 1-acid glycoprotein gene via direct protein-protein interaction. AB - The acute-phase reaction is accompanied by an increase in a variety of serum proteins, named acute-phase proteins. The synthesis of these proteins is synergistically controlled by glucocorticoids and inflammatory cytokines such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor alpha. Recently, we have cloned nuclear factor-IL-6 (NF-IL6), a transcription factor that activates the IL 6 gene, and have demonstrated its involvement in the expression of acute-phase protein genes. We report here an analysis of the molecular mechanisms by which inflammatory cytokines and glucocorticoid act synergistically to activate expression of the rat alpha 1-acid glycoprotein (AGP) gene. We found that NF-IL6 and ligand-activated rat glucocorticoid receptor acted synergistically to transactivate the AGP gene and that maximal transcriptional activation of the AGP gene required expression of both intact NF-IL6 and rat glucocorticoid receptor. Surprisingly, however, transcriptional synergism was still observed even when one of the two factors lacked either its DNA-binding or transcriptional-activation function. We present evidence for a direct protein-protein interaction between these two distinct transcription factors and propose that this may be responsible for the synergistic activation of the rat AGP gene. PMID- 8441419 TI - PRP19: a novel spliceosomal component. AB - We have isolated the gene of a splicing factor, PRP19, by complementation of the temperature-sensitive growth defect of the prp19 mutant of Saccharomyces cerevisiae. The gene encodes a protein of 502 amino acid residues of molecular weight 56,500, with no homology to sequences in the data base. Unlike other PRP proteins or mammalian splicing factors, the sequence of PRP19 has no discernible motif. Immunoprecipitation studies showed that PRP19 is associated with the spliceosome during the splicing reaction. Although the exact function of PRP19 remains unknown, PRP19 appears to be distinct from the other PRP proteins or other spliceosomal components. PMID- 8441420 TI - Nonsense codons can reduce the abundance of nuclear mRNA without affecting the abundance of pre-mRNA or the half-life of cytoplasmic mRNA. AB - The abundance of the mRNA for human triosephosphate isomerase (TPI) is decreased to approximately 20% of normal by frameshift and nonsense mutations that cause translation to terminate at a nonsense codon within the first three-fourths of the reading frame. Results of previous studies inhibiting RNA synthesis with actinomycin D suggested that the decrease is not attributable to an increased rate of cytoplasmic mRNA decay. However, the step in TPI RNA metabolism that is altered was not defined, and the use of actinomycin D, in affecting all polymerase II-transcribed genes, could result in artifactual conclusions. In data presented here, the nonsense codon-mediated reduction in the level of TPI mRNA is shown to be characteristic of both nuclear and cytoplasmic fractions of the cell, indicating that the altered metabolic step is nucleus associated. Neither aberrancies in gene transcription nor aberrancies in RNA splicing appear to contribute to the reduction since there were no accompanying changes in the amount of nuclear run-on transcription, the level of any of the six introns in TPI pre-mRNA, or the size of processed mRNA in the nucleus. Deletion of all splice sites that reside downstream of a nonsense codon does not abrogate the reduction, indicating that the reduction takes place independently of the splicing of a downstream intron. Experiments that placed TPI gene expression under the control of the human c-fos promoter, which can be transiently activated by the addition of serum to serum-deprived cells, verified that there is no detectable effect of a nonsense codon on the turnover of cytoplasmic mRNA. PMID- 8441421 TI - Epidermal growth factor regulates the exchange rate of guanine nucleotides on p21ras in fibroblasts. AB - Treatment of intact Rat-1 fibroblasts with epidermal growth factor (EGF) leads to rapid activation of cellular ras-encoded proteins. By using the bacterial toxin streptolysin O to permeabilize these cells, it was shown that the low basal rate at which guanine nucleotides bind to, and dissociate from, ras-encoded protein in quiescent fibroblasts was greatly accelerated by EGF treatment. Nucleotide binding to other proteins was not affected. Stimulation of nucleotide exchange on ras-encoded protein required tyrosine kinase but not phospholipase activity. EGF had no effect on total GTPase-activating protein activity. Regulation of ras encoded protein in Rat-1 fibroblasts is therefore mediated by stimulation, either directly or indirectly, of ras-encoded protein-specific guanine nucleotide exchange factors by the EGF receptor tyrosine kinase. PMID- 8441422 TI - The NFAT-1 DNA binding complex in activated T cells contains Fra-1 and JunB. AB - Activation of T cells induces transcription of the interleukin-2 (IL-2) gene. IL 2 expression is regulated through the binding of transcription factors to multiple sites within the IL-2 enhancer. One such cis-acting element within the IL-2 enhancer is the NFAT-1 (nuclear factor of activated T cells) binding site. NFAT-1 binding activity is absent in resting cells but is induced upon T-cell activation. The induction of NFAT-1 binding activity can be inhibited by cyclosporin A, potentially accounting for the ability of cyclosporin A to inhibit IL-2 production by T cells. We have previously reported that the NFAT-1 binding complex is composed of at least two proteins and that the 5' portion of the NFAT 1 sequence acts as a binding site for one or more proteins from the Ets family of transcription factors. We now report that the 3' portion of the NFAT-1 sequence contains a variant AP-1 binding site. NFAT-1 binding can be specifically inhibited by oligonucleotides containing a consensus AP-1 site. Moreover, mutation of the AP-1 site at the 3' end of the NFAT-1 sequence inhibits both NFAT 1 binding and the ability of the NFAT-1 binding site to activate expression from a reporter plasmid upon T-cell activation. Since AP-1 sites bind dimeric protein complexes composed of individual members of the Fos and Jun families of transcription factors, we used antibodies specific for individual Fos and Jun family members to determine whether they are present in the NFAT-1 binding complex. These experiments demonstrated that the NFAT-1 binding complex contains JunB and Fra-1 proteins. Northern (RNA) blot analyses demonstrate that both fra-1 and junB mRNAs are induced upon T-cell activation, although fra-1 mRNA is present even in quiescent T cells. Of interest, junB is not expressed in quiescent T cells, and it is induced with kinetics that are similar to those for the induction of IL-2 mRNA expression. Taken together, these results suggested that the JunB-Fra-1 heterodimer is the inducible nuclear component of the NFAT-1 binding activity and that JunB expression regulates the formation of the heterodimer. In addition, these data indicated that specific heterodimers of Fos and Jun family members may have selective roles in the induction of transcription during cellular activation. PMID- 8441423 TI - Evidence that GCD6 and GCD7, translational regulators of GCN4, are subunits of the guanine nucleotide exchange factor for eIF-2 in Saccharomyces cerevisiae. AB - Starvation of the yeast Saccharomyces cerevisiae for an amino acid signals increased translation of GCN4, a transcriptional activator of amino acid biosynthetic genes. We have isolated and characterized the GCD6 and GCD7 genes and shown that their products are required to repress GCN4 translation under nonstarvation conditions. We find that both GCD6 and GCD7 show sequence similarities to components of a high-molecular-weight complex (the GCD complex) that appears to be the yeast equivalent of translation initiation factor 2B (eIF 2B), which catalyzes GDP-GTP exchange on eIF-2. Furthermore, we show that GCD6 is 30% identical to the largest subunit of eIF-2B isolated from rabbit reticulocytes. Deletion of either GCD6 or GCD7 is lethal, and nonlethal mutations in these genes increase GCN4 translation in the same fashion described for defects in known subunits of eIF-2 or the GCD complex; derepression of GCN4 is dependent on short open reading frames in the GCN4 mRNA leader and occurs independently of eIF-2 alpha phosphorylation by protein kinase GCN2, which is normally required to stimulate GCN4 translation. Together, our results provide evidence that GCD6 and GCD7 are subunits of eIF-2B in S. cerevisiae and further implicate this GDP-GTP exchange factor in gene-specific translational control. PMID- 8441424 TI - A human mitochondrial transcriptional activator can functionally replace a yeast mitochondrial HMG-box protein both in vivo and in vitro. AB - Human mitochondrial transcription factor A is a 25-kDa protein that binds immediately upstream of the two major mitochondrial promoters, thereby leading to correct and efficient initiation of transcription. Although the nature of yeast mitochondrial promoters is significantly different from that of human promoters, a potential functional homolog of the human transcriptional activator protein has been previously identified in yeast mitochondria. The importance of the yeast protein in yeast mitochondrial DNA function has been shown by inactivation of its nuclear gene (ABF2) in Saccharomyces cerevisiae cells resulting in loss of mitochondrial DNA. We report here that the nuclear gene for human mitochondrial transcription factor A can be stably expressed in yeast cells devoid of the yeast homolog protein. The human protein is imported efficiently into yeast mitochondria, is processed correctly, and rescues the loss-of-mitochondrial DNA phenotype in a yeast abf2 strain, thus functionally substituting for the yeast protein. Both human and yeast proteins affect yeast mitochondrial transcription initiation in vitro, suggesting that the two proteins may have a common role in this fundamental process. PMID- 8441425 TI - The alpha-mating type locus of Cryptococcus neoformans contains a peptide pheromone gene. AB - The opportunistic fungal pathogen Cryptococcus neoformans has two mating types, MATa and MAT alpha. The MAT alpha strains are more virulent. Mating of opposite mating type haploid yeast cells results in the production of a filamentous hyphal phase. The MAT alpha locus has been isolated in this study in order to identify the genetic differences between mating types and their contribution to virulence. A 138-bp fragment of MAT alpha-specific DNA which cosegregates with alpha-mating type was isolated by using a difference cloning method. Overlapping phage and cosmid clones spanning the entire MAT alpha locus were isolated by using this MAT alpha-specific fragment as a probe. Mapping of these clones physically defined the MAT alpha locus to a 35- to 45-kb region which is present only in MAT alpha strains. Transformation studies with fragments of the MAT alpha locus identified a 2.1-kb XbaI-HindIII fragment that directs starvation-induced filament formation in MATa cells but not in MAT alpha cells. This 2.1-kb fragment contains a gene, MF alpha, with a small open reading frame encoding a pheromone precursor similar to the lipoprotein mating factors found in Saccharomyces cerevisiae, Ustilago maydis, and Schizosaccharomyces pombe. The ability of the MATa cells to express, process, and secrete the MAT alpha pheromone in response to starvation suggests similar mechanisms for these processes in both cell types. These results also suggest that the production of pheromone is under a type of nutritional control shared by the two cell types. PMID- 8441426 TI - The effect of varying levels of outdoor-air supply on the symptoms of sick building syndrome. AB - BACKGROUND: The sick building syndrome is the term given to a constellation of symptoms reported by workers in modern office buildings, hypothesized to occur when the supply of outdoor air is reduced, because of the accumulation of contaminants arising from within the building. We undertook this study to determine the effect of changing the supply of outdoor air in four office buildings on the symptoms reported by workers and their perception of the indoor environment. METHODS: Within each of three consecutive two-week blocks, the ventilation systems in each building were manipulated, in random order, to deliver to the indoor environment an intended 20 or 50 ft3 (0.57 or 1.4 m3) of outdoor air per minute per person for one week at a time. Each week, the participants, unaware of the experimental intervention, reported symptoms and the indoor environment was thoroughly evaluated. RESULTS: Of 1838 eligible workers in the four buildings, 1546 (84 percent) participated in the study. The supply of outdoor air averaged 7 percent and 32 percent in the ventilation systems and 30 and 64 ft3 (0.85 and 1.8 m3) per minute per person in the work sites at the lower and higher ventilation levels, respectively. These changes in the supply of outdoor air were not associated with changes in the participants' ratings of the office environment or in symptom frequency (crude odds ratio, 1.0; 95 percent confidence interval, 0.9 to 1.1). After work-site measures of ventilation, temperature, humidity, and air velocity were included in the regression analysis, the adjusted odds ratio was also 1.0 (95 percent confidence interval, 0.8 to 1.2). CONCLUSIONS: Increases in the supply of outdoor air did not appear to affect workers' perceptions of their office environment or their reporting of symptoms considered typical of the sick building syndrome. PMID- 8441428 TI - Effects of stimulus intensity and electrode placement on the efficacy and cognitive effects of electroconvulsive therapy. AB - BACKGROUND: The efficacy of electroconvulsive therapy in major depression is established, but the importance of the electrical dosage and electrode placement in relation to efficacy and side effects is uncertain. METHODS: In a double-blind study, we randomly assigned 96 depressed patients to receive right unilateral or bilateral electroconvulsive therapy at either a low electrical dose (just above the seizure threshold) or a high dose (2.5 times the threshold). Symptoms of depression and cognitive functioning were assessed before, during, immediately after, and two months after therapy. Patients who responded to treatment were followed for one year to assess the rate of relapse. RESULTS: The response rate for low-dose unilateral electroconvulsive therapy was 17 percent, as compared with 43 percent for high-dose unilateral therapy (P = 0.054), 65 percent for low dose bilateral therapy (P = 0.001), and 63 percent for high-dose bilateral therapy (P = 0.001). Regardless of electrode placement, high dosage resulted in more rapid improvement (P < 0.05). Compared with the low-dose unilateral group, the high-dose unilateral group took 83 percent longer (P < 0.001) to recover orientation after seizure induction, whereas the combined bilateral groups took 252 percent longer (P < 0.001). During the week after treatment, there was three times more retrograde amnesia about personal information with bilateral therapy (P < 0.001). There were no differences between treatment groups in cognitive effects two months after treatment. Forty-one of the 70 patients who responded to therapy (59 percent) relapsed, and there were no differences between treatment groups. CONCLUSIONS: Increasing the electrical dosage increases the efficacy of right unilateral electroconvulsive therapy, although not to the level of bilateral therapy. High electrical dosage is associated with a more rapid response, and unilateral treatment is associated with less severe cognitive side effects after treatment. PMID- 8441427 TI - A prospective study of dietary calcium and other nutrients and the risk of symptomatic kidney stones. AB - BACKGROUND: A high dietary calcium intake is strongly suspected of increasing the risk of kidney stones. However, a high intake of calcium can reduce the urinary excretion of oxalate, which is thought to lower the risk. The concept that a higher dietary calcium intake increases the risk of kidney stones therefore requires examination. METHODS: We conducted a prospective study of the relation between dietary calcium intake and the risk of symptomatic kidney stones in a cohort of 45,619 men, 40 to 75 years of age, who had no history of kidney stones. Dietary calcium was measured by means of a semiquantitative food-frequency questionnaire in 1986. During four years of follow-up, 505 cases of kidney stones were documented. RESULTS: After adjustment for age, dietary calcium intake was inversely associated with the risk of kidney stones; the relative risk of kidney stones for men in the highest as compared with the lowest quintile group for calcium intake was 0.56 (95 percent confidence interval, 0.43 to 0.73; P for trend, < 0.001). This reduction in risk decreased only slightly (relative risk, 0.66; 95 percent confidence interval, 0.49 to 0.90) after further adjustment for other potential risk factors, including alcohol consumption and dietary intake of animal protein, potassium, and fluid. Intake of animal protein was directly associated with the risk of stone formation (relative risk for men with the highest intake as compared with those with the lowest, 1.33; 95 percent confidence interval, 1.00 to 1.77); potassium intake (relative risk, 0.49; 95 percent confidence interval, 0.35 to 0.68) and fluid intake (relative risk, 0.71; 95 percent confidence interval, 0.52 to 0.97) were inversely related to the risk of kidney stones. CONCLUSIONS: A high dietary calcium intake decreases the risk of symptomatic kidney stones. PMID- 8441429 TI - Association between high levels of expression of the TRK gene and favorable outcome in human neuroblastoma. AB - BACKGROUND AND METHODS: The nerve growth factor receptor is expressed in some neuroblastomas, in which its primary component is encoded by the TRK protooncogene. To determine the relation of the expression of TRK messenger RNA in neuroblastomas to other clinical and laboratory variables, we studied frozen tumor samples from 77 patients. In addition, we tested two primary neuroblastomas that expressed TRK for responsiveness to nerve growth factor. RESULTS: TRK expression strongly correlated with favorable tumor stage (I, II, and IVS vs. III and IV), younger age (< 1 year vs. > or = 1 year), normal N-myc copy number, and low level of N-myc expression. N-myc amplification (indicated by a high copy number) correlated with advanced tumor stage, older age, an adrenal site of the primary tumor, low level of expression of TRK, and high level of expression of N myc. Analysis of five-year cumulative-survival rates demonstrated an association of a very favorable outcome with a high level of TRK expression (86 percent vs. 14 percent) and with normal N-myc copy number (84 percent vs. 0 percent). Univariate analysis showed that these two variables were the most powerful predictors of outcome (chi-square = 51.30, P < 0.001; and chi-square = 93.61, P < 0.001, respectively). TRK expression still had significant prognostic value when the analysis was restricted to tumors without N-myc amplification. In primary cultures of neuroblastoma cells expressing TRK, exposure to nerve growth factor induced early gene expression and neurite outgrowth, but deprivation of nerve growth factor led to neuronal cell death. CONCLUSIONS: A high level of expression of the TRK proto-oncogene in a neuroblastoma is strongly predictive of a favorable outcome. A tumor with a functional nerve growth factor receptor may be dependent on the neurotrophin nerve growth factor for survival and may regress in its absence, allowing a new approach to the treatment of certain patients with neuroblastoma. PMID- 8441430 TI - Pulmonary surfactant therapy. PMID- 8441431 TI - The sick building syndrome in office buildings--a breath of fresh air. PMID- 8441432 TI - Magnetic resonance coronary angiography--assessing an emerging technology. PMID- 8441433 TI - Composition of the diet and calcium kidney stones. PMID- 8441434 TI - Electroconvulsive therapy--a modern medical procedure. PMID- 8441435 TI - Patient access to magnetic resonance imaging centers in Orange County, California. PMID- 8441436 TI - Venous thrombosis and cancer. PMID- 8441437 TI - Venous thrombosis and cancer. PMID- 8441438 TI - Venous thrombosis and cancer. PMID- 8441439 TI - Psychosocial support during high-risk pregnancy. PMID- 8441440 TI - Psychosocial support during high-risk pregnancy. PMID- 8441441 TI - Psychosocial support during high-risk pregnancy. PMID- 8441442 TI - More on vaginal inflammation in Africa. PMID- 8441443 TI - More on vaginal inflammation in Africa. PMID- 8441444 TI - Endocrine effects of HIV infection. PMID- 8441445 TI - Endocrine effects of HIV infection. PMID- 8441446 TI - Endocrine effects of HIV infection. PMID- 8441447 TI - Managed care or mangled care? PMID- 8441448 TI - Margarita photodermatitis. PMID- 8441449 TI - The American health care system--Medicaid. PMID- 8441450 TI - Preview of 1994 US budget emphasizes big projects. PMID- 8441451 TI - French move past Genethon to gene-therapy research. PMID- 8441452 TI - Japanese panel proposes extension of cancer research. PMID- 8441453 TI - Leprosy researchers lament suppression of Indian paper. PMID- 8441454 TI - McBride found guilty of fraud. PMID- 8441455 TI - French AIDS team wins Faisal Prize. PMID- 8441456 TI - Global project under way to sample genetic diversity. PMID- 8441457 TI - Diet and cancer. PMID- 8441458 TI - More interferons. PMID- 8441459 TI - Human genetics. Penetrating the peroxisome. PMID- 8441460 TI - DNA replication. Methyltransferases in foci. PMID- 8441461 TI - Viral transactivation. Pleiotropy and henchman X. PMID- 8441462 TI - Conservation genetics. Breeding like flies. PMID- 8441463 TI - Dental HIV transmission? PMID- 8441464 TI - More protein talk. PMID- 8441465 TI - A sensory role for neuronal growth cone filopodia. AB - The dynamic nature of neuronal growth cone filopodia led to the suggestion that the primary function of filopodia is to sample their immediate environment, responding to and transducing environmental signals that affect growth cone behaviour and shape. Filopodia seem well suited to serve as antenna-like sensors, their broad span allows sampling of information over a greatly enhanced radius, and forward-projecting filopodia encounter potential cues in the molecular terrain long before the advancing growth cone itself. Filopodia in culture can serve structural roles, exert mechanical tension and selectively adhere to their surrounding. Whether or not filopodia have a general sensory role has not been tested directly, largely because of their small size, which limits an electrophysiological approach, and their integral relationship with the parent growth cone, which prevents resolution of their different functions. Here we use surgical procedures to isolate individual filopodia from their parent growth cone and, by monitoring their morphology and calcium second messenger systems, we show that neuronal growth cone filopodia contain signal transduction mechanisms that allow autonomous responses and the transmission of distant environmental information to their parent growth cone. PMID- 8441466 TI - Retinal age pigments generated by self-assembling lysosomotropic detergents. AB - A universal biomarker of cellular ageing in eukaryotic postmitotic cells is the appearance over time of autofluorescent lysosomal residual bodies called age pigments or lipofuscin granules. Their role in the process of cellular ageing has been debated without resolution. Neither the identity nor mechanism of formation of the fluorophores has been definitively determined. A postmitotic cell type that accumulates large quantities of age pigments is the ocular retinal pigment epithelium. We have now identified the major orange-emitting fluorophore of these pigments using fast-atom bombardment tandem mass spectrometry with collisional activation analysis. It is an amphoteric quaternary amine that arises as a Schiff base reaction product of retinaldehyde and ethanolamine. This compound should display lysosomotropic detergent behaviour which would help explain many of the age-related changes shown in this cell. These results suggest a new role for Schiff base reaction products as lysosomotropic amines in the genesis of cellular age pigments. PMID- 8441467 TI - Putative X-linked adrenoleukodystrophy gene shares unexpected homology with ABC transporters. AB - Adrenoleukodystrophy (ALD) is an X-linked disease affecting 1/20,000 males either as cerebral ALD in childhood or as adrenomyeloneuropathy (AMN) in adults. Childhood ALD is the more severe form, with onset of neurological symptoms between 5-12 years of age. Central nervous system demyelination progresses rapidly and death occurs within a few years. AMN is a milder form of the disease with onset at 15-30 years of age and a more progressive course. Adrenal insufficiency (Addison's disease) may remain the only clinical manifestation of ALD. The principal biochemical abnormality of ALD is the accumulation of very long-chain fatty acids (VLCFA) because of impaired beta-oxidation in peroxisomes. The normal oxidation of VLCFA-CoA in patients' fibroblasts suggested that the gene coding for the VLCFA-CoA synthetase could be a candidate gene for ALD. Here we use positional cloning to identify a gene partially deleted in 6 of 85 independent patients with ALD. In familial cases, the deletions segregated with the disease. An identical deletion was detected in two brothers presenting with different clinical ALD phenotypes. Candidate exons were identified by computer analysis of genomic sequences and used to isolate complementary DNAs by exon connection and screening of cDNA libraries. The deduced protein sequence shows significant sequence identity to a peroxisomal membrane protein of M(r) 70K that is involved in peroxisome biogenesis and belongs to the 'ATP-binding cassette' superfamily of transporters. PMID- 8441468 TI - A secreted protein kinase of Yersinia pseudotuberculosis is an indispensable virulence determinant. AB - Phosphorylation of proteins catalysed by protein kinases is associated with central functions in growth and proliferation of the eukaryotic cell, and kinases are particularly important in the signal transduction pathways. Enterobacterial protein kinases are structurally and functionally different from eukaryotic protein kinases, and no prokaryotic kinase has so far been described implicating a direct role for this activity in virulence. Virulent Yersinia possess a common virulence plasmid that encodes a number of secreted proteins (Yops), of which YopH has protein-tyrosine phosphatase activity with a key function in the block of phagocytosis by the pathogen. Here we report that the virulence plasmid of Yersinia pseudotuberculosis encodes a secreted protein kinase (YpkA) with extensive homology to eukaryotic Ser/Thr protein kinases. Specific mutants of ypkA resulted in avirulent strains. Thus, YpkA is, to our knowledge, the first reported prokaryotic secreted protein kinase involved in pathogenicity, presumably by interfering with the signal transduction pathways of the target cell. PMID- 8441469 TI - A yeast GTPase-activating protein that interacts specifically with a member of the Ypt/Rab family. AB - Members of the Ras superfamily of GTP-binding proteins are involved in a variety of cellular processes, including signal transduction, cytoskeletal organization and protein transport. GTP-binding proteins of the Ypt/Rab family direct vesicular protein transport in the secretory and endocytic pathways in the yeast Saccharomyces cerevisiae (Ypt proteins) and in mammalian systems (Rab proteins). The cellular activity of monomeric GTP-binding proteins is influenced by proteins that regulate GDP/GTP exchange and GTP hydrolysis. GTPase-activating proteins (GAPs) can increase the slow intrinsic GTPase activity of GTP-binding proteins by several orders of magnitude. As GAPs modulate the activity of GTP-binding proteins, they are thought to give a biochemical handle on the functioning of Ypt/Rab proteins in transport vesicle budding and docking or fusion at donor and acceptor membranes. We report here the first cloned GTPase-activating protein for the Ypt/Rab protein family. The gene, GYP6 (GAP of Ypt6 protein), encodes a protein of 458 amino acids which is highly specific for the Ypt6 protein and shows little or no cross-reactivity with other Ypt/Rab family members or with H Ras p21. PMID- 8441470 TI - Conversion of lytic to persistent alphavirus infection by the bcl-2 cellular oncogene. AB - Little is known about virus-host cell interactions that regulate the lytic potential of viruses during productive replication. Sindbis virus (SV), a single stranded positive-sense RNA virus in the alphavirus genus (family Togaviridae), results in lytic infection in most vertebrate cell lines, but persistent productive infection in post-mitotic neurons. The cellular oncogene bcl-2, which encodes an inner mitochondrial membrane protein of M(r) 26,000 (ref. 2), blocks programmed cell death (apoptosis) in neurons. We therefore investigated whether SV infection induces programmed cell death in non-neuronal cells, and if so, whether virus-induced programmed cell death can be blocked by transfection with bcl-2. We demonstrate that SV infection of baby hamster kidney (BHK-2), mouse neuroblastoma (N18), and rat prostatic adenocarcinoma (AT-3) cells results in programmed cell death, whereas SV infection of bcl-2-transfected AT-3 cells results in long-term persistent productive infection. Thus cellular bcl-2 oncogene expression plays a role in the establishment of persistent viral infection by blocking virus-induced programmed cell death. PMID- 8441471 TI - Hepatitis B virus transactivator HBx uses a tumour promoter signalling pathway. AB - The hepatitis B virus (HBV) transactivator protein HBx is enigmatic in that it stimulates a striking variety of promoters which do not share a common cis regulatory element. As it does not bind to DNA, it has been speculated that HBx acts indirectly through cellular pathways. Under certain conditions HBx can have an oncogenic potential, which may be relevant for HBV-associated liver carcinogenesis, but until now the mechanism for transactivation and cell transformation by HBx was unclear. We report here that HBx uses a complex signal transduction pathway for transactivation. An increase in the endogenous protein kinase C (PKC) activator sn-1,2-diacylglycerol and the subsequent activation of PKC give rise to activation of the transcription factor AP-1 (Jun-Fos). As a result, HBx transactivates through binding sites for AP-1 and other PKC-dependent transcription factors (AP-2, NF-kappa B), thereby explaining the as-yet incomprehensible variety of HBx-inducible genes. As the PKC signal cascade also mediates cell transformation by tumour-promoting agents, the mechanism presented here might account for the oncogenic potential of HBx. PMID- 8441472 TI - Local domains of supercoiling activate a eukaryotic promoter in vivo. AB - Experiments correlating template topology with transcriptional activity suggest that DNA topology plays a role in eukaryotic gene expression. Linear templates transfected into cultured cells produce far fewer transcripts than do circular transcription templates, and no transcripts can be detected from linear templates injected into Xenopus oocytes. Further, when transcriptionally active circular templates in Xenopus oocytes are linearized by injection of a restriction enzyme, transcription dramatically decreases. Here we show that transcription by phage T7 RNA polymerase from a divergent promoter can partially replace the requirement for circular Xenopus ribosomal RNA transcription templates in Xenopus oocytes. Supercoiled domains can apparently be generated on short pieces of DNA having no known sequences that result in association with the nuclear architecture, suggesting that localized, transient domains of supercoiling fulfil the minimum topological needs for Xenopus rRNA transcription in vivo. PMID- 8441473 TI - Magnetic bead capture of expressed sequences encoded within large genomic segments. AB - Magnetic bead capture utilizes biotin-streptavidin magnetic bead technology to isolate cDNAs rapidly from large genomic intervals, giving several thousand-fold enrichment of the selected cDNAs. The technique can allow parallel analysis of several large genomic segments of varying complexities and can be applied to the isolation of expressed sequences from various tissue sources. PMID- 8441474 TI - US drug industry's research support. PMID- 8441475 TI - Japan's foundations still building. PMID- 8441476 TI - Looking towards the West. PMID- 8441477 TI - The European pharmaceutical outlook. PMID- 8441478 TI - Making partnerships work. PMID- 8441479 TI - "Bad problem--worse solution". PMID- 8441480 TI - "Health care in the nineties". PMID- 8441481 TI - Post-traumatic epilepsy. PMID- 8441482 TI - Pre-operative staging of colorectal carcinoma using positron emission tomography. AB - Positron emission tomography (PET) is a unique technique for imaging functional metabolism of normal and diseased tissue. Accelerated rate of glucose metabolism typical of malignant tumor cells can be detected by using fluorine-18 deoxyglucose. In this pilot study, PET FDG imaging was compared to computerized tomography for the pre-operative staging of colorectal carcinoma. We prospectively evaluated 16 patients by simultaneously performing PET FDG and CT imaging for lesions in the liver, colon and rectum. The results were compared to the operative findings in all patients. Twenty tumor sites (lymph nodes 5, colon and rectum 13, liver 2) were found on histology in 16 patients. On comparison with histology, sensitivity, specificity and predictive accuracy for detection of tumor sites were 90%, 66% and 87% with PET as compared to 60%, 100%, and 65% with CT. These findings represent increased sensitivity and predictive accuracy for staging of colorectal carcinoma with PET FDG imaging as compared to CT scanning. PMID- 8441483 TI - Nebraska outpatient care quality assessment. AB - Nebraska Hospital Market Areas (HMAs) with significantly and consistently high admission rates for Ambulatory Care Sensitive Conditions (ACSC) were identified using the Blue Cross and Blue Shield of Nebraska (BCBSN) small area analysis data. Two-thirds of those hospitalized were surveyed by Wiese Research of Omaha, Nebraska to determine if the cause for the high admission rates was related to outpatient care quality. BCBSN members living in HMAs without high admission rates were also surveyed for comparison purposes. The survey revealed that satisfaction with outpatient care was high, and that access (geographic or financial) was not a problem for either the test or control group. The test group did delay (for a short time) obtaining outpatient care when compared to the control group. Most of the control group stated that they obtained outpatient care the day symptoms started. Although the majority of the test group obtained outpatient care within a week, they were not as prompt in obtaining outpatient care as the control group. The types of conditions studied (ACSCS) are conditions that can rapidly become severe, therefore prompt treatment is imperative. The main reason given for chronic delays of both groups were that the condition "suddenly became serious." There may be implications for providers to use more "compliance-gaining" strategies in problem area, and for insurers to offer contract endorsements which would encourage members to obtain prompt treatment and preventive healthcare. PMID- 8441484 TI - Neonatal transport. PMID- 8441485 TI - Laparoscopic surgery in the military. PMID- 8441486 TI - Organization and doctrine for a medical platoon. PMID- 8441487 TI - Organization and doctrine for a medical platoon. PMID- 8441488 TI - Laws of war. PMID- 8441489 TI - Use of knee and elbow pads during Ranger training. PMID- 8441490 TI - Pulsed, non-thermal, high-frequency electromagnetic energy (DIAPULSE) in the treatment of grade I and grade II ankle sprains. AB - Acutely sprained ankles represent a frequent and common injury among active duty troops in training, and are a significant source of morbidity with respect to days lost to training. Swelling in the form of periarticular edema limits motion, causes pain, prevents wearing of normal foot gear, and slows the healing process. Reduction of edema was attempted in acutely sprained ankles by the use of pulsed electromagnetic energy (Diapulse). In a randomized, prospective, double blind study of 50 grade I and II (no gross instability) sprained ankles, a statistically significant (p < 0.01) decrease in edema was noted following one treatment with Diapulse. The application of this modality in acutely sprained ankles could result in significant decreases in time lost to military training. PMID- 8441491 TI - The role of the United States Army active component pediatricians in Operations Desert Shield, Desert Storm, and provide comfort. AB - The professional activities and experiences of Army active component pediatricians deployed to Southwest Asia in support of Operations Desert Shield, Desert Storm, and Provide Comfort are reported. The 37 pediatricians who served in Southwest Asia were surveyed by a voluntary questionnaire. The survey revealed that Army pediatricians played an important role in these operations and in supporting the combat forces in Southwest Asia. They also played a critical role in caring for children displaced by the war and its aftermath in southern and northern Iraq. Pediatricians played an equally important role in continuing to provide care and support for the family members left behind in the United States and Europe. PMID- 8441492 TI - Medical evacuation experience of two 7th Corps medical companies supporting Desert Shield/Desert Storm. AB - Examining medical evacuation data in the high-intensity conflict environment of Desert Shield/Desert Storm yielded some interesting findings. Motor vehicle accidents accounted for most precombat injuries. The combat period was markedly more intense than the other periods and must be the focal point for planning. Indigenous civilians and prisoners of war accounted for a large portion of casualties during and after the combat phases. Mission coordination was a major problem until a central dispatch agency was organized. Ambulance exchange points lacked communication and triage capability, limiting multiple patient transfer and long-haul efficiency. Other problems included lack of translators for civilian casualties and inadequate passenger restraints in some ground vehicles. PMID- 8441493 TI - Delayed hemorrhage as a manifestation of occult vascular injury. PMID- 8441494 TI - Cases of Lyme disease reported in a military community. AB - Lyme disease, a growing public health problem in the United States, is also an increasing threat in Europe. Cases identified in a military community in West Germany are presented and problems of diagnosis and treatment discussed. PMID- 8441495 TI - Bowel obstruction from retained inner bumper following removal of gastrostomy tube: a case report. AB - Percutaneous endoscopic gastrostomy is an effective means of obtaining enteral access in patients who need chronic nutritional support. We describe a complication resulting from the inability to remove an inner bumper. This bumper migrated into the terminal ileum, where it lodged, causing bowel obstruction. Literature review revealed no reports of similar complications. PMID- 8441496 TI - Applying ATLS to the Gulf War. AB - During a 3-month deployment to Silopi, Turkey, for Operation Provide Comfort, the 39 TACG Air Transportable Hospital (ATH) managed 32 cases of severe military trauma. Fifty-two operations were necessary, 78% of which were performed at the ATH. Advanced Trauma Life Support (ATLS) protocols were applied to all of the patients. Only 14% of the 52 procedures were ATLS-learned skills. Also, only 30% of the patients could be managed solely by ATLS in the first 6 hours, the average time of ATH responsibility. ATLS alone is insufficient wartime readiness preparation for the military physician. PMID- 8441497 TI - A case report of painful oral ulcerations associated with the use of alpha interferon in a patient with chronic hepatitis due to non-A non-B non-C virus. AB - The following case report is of a patient who received alpha interferon for non A, non-B, non-C chronic hepatitis and developed severe painful oral ulcerations associated with inanition and weight loss. The association of painful oral ulcerations with interferon therapy has not been reported before. PMID- 8441498 TI - The Patient Self-Determination Act: is it all it can be? PMID- 8441499 TI - Against medical advice: Part I, A review of the literature. AB - As a preliminary step to studying the Army's experience with against medical advice (AMA) discharges, the literature was reviewed. Fifty-one articles were found through a computer program search. These articles reported widely varying rates depending upon the type of patient, primary diagnosis, and type of setting. Patients with drug and/or alcohol abuse problems are at significantly higher risk for AMA. No civilian studies have been identified which evaluate long-term trends. PMID- 8441500 TI - Against medical advice: Part II, The Army experience 1971-1988. AB - The Army experience with discharges against medical advice (AMA) from 1971 to 1988 is analyzed. AMA discharges have declined in a statistically significant manner in both medical centers and community hospitals. Discharges have decreased among men but increased among women. AMA discharges have decreased for both blacks and whites. Among clinical services, only obstetrics and gynecology demonstrated statistically significant increases. Among patient categories, only family members showed an increase. The possible sources of these various changes are discussed. PMID- 8441501 TI - Variables related to the psychological well being of Army wives during the stress of an extended military separation. AB - Past research has indicated that extended military separations have a profound impact on military wives. The present study examines the relationship between self-esteem, locus of control, accumulated stressors, perceived military stress, and the psychological well-being of 74 Army wives whose husbands were stationed in the Persian Gulf. Accumulated stressors and perceived military stress were able to account for a significant portion of the variance in psychological well being. This suggests that during an extended separation, the lower the accumulation of stressors and perceived military stress, the greater the psychological well-being of Army wives. Clinical implications of these findings are discussed. PMID- 8441502 TI - The role of hyperbaric oxygenation in the treatment of clostridial myonecrosis. AB - Hyperbaric oxygenation as an adjunct in the treatment of clostridial myonecrosis (gas gangrene) has been used extensively in facilities with hyperbaric chambers. The United States Air Force has had extensive experience in the treatment of clostridial myonecrosis, treating 77 patients since 1965. This study reviews the experience in the treatment of this disease process in military multiplace hyperbaric chambers and provides an in-depth analysis of factors affecting patient survival. A comprehensive review of the literature on the treatment of clostridial myonecrosis with hyperbaric oxygenation is presented in this paper. PMID- 8441503 TI - Preparing for the downsizing and closure of Letterman Army Medical Center: a case study. AB - Letterman Army Medical Center (LAMC) began a phased downsizing in July 1991 which will lead to closure by June 30, 1994. An analysis of the downsizing and closure process has yielded information which can be valuable to medical treatment facility managers faced with similar challenges in the future. By review and analysis of documentation, this case study extracted and interpreted pertinent information from historical records and from personnel involved in planning for the downsizing and closure of LAMC. This study provides managers of military hospitals that are downsizing or closing with a summary of issues for planning, compiled by their relative importance, and a description of methods employed by LAMC for managing these issues. PMID- 8441504 TI - Esophagogastroduodenoscopy in a small Army community hospital. AB - This is a review of the use of esophagogastroduodenoscopy (EGD) in a small Army community hospital. The method used was retrospective review of all patients who had EGD during a 4-month period. Patient demographics, indications for the procedure, and diagnoses were topics monitored. The most frequent indication for EGD was recurrent dyspepsia in patients already on H2 blockers. The most common diagnosis was gastritis and "gross" observation by examiners closely correlated with histologic diagnosis. EGD is performed for standard indications on a variety of patients at Cutler Army Community Hospital. Normal exams occurred at an acceptable rate and histological correlation with "gross" appearance was good. PMID- 8441505 TI - Establishment of an assisted reproduction program in the Armed Forces. AB - Approximately one in seven couples are infertile. Half of these couples fail to conceive following conventional therapies. Recently, technologies have evolved which provide hope to these couples and lead to cumulative pregnancy rates of 65%. An assisted reproduction (AR) program has recently been established at Wilford Hall Medical Center. The reproductive endocrinologists, on-service residents, and clinic support staff are responsible for all aspects of care including stimulation, retrieval, andrology, embryology, and transfer. To date, there have been 104 transfers with 28 pregnancies. In summary, AR is available in the Armed Forces and allows infertile couples to receive state-of-the-art health care. PMID- 8441506 TI - Pharmacy: the Saudi experience. AB - At deployment plus 60 days, we were busy preparing for the possibility of war while simultaneously providing pharmaceutical service for more than 25,000 people. We were anticipating the arrival of a new Deployable Medical Systems hospital, increased automation in the form of the Tri-Service Micro Pharmacy Computer system, and various improvements in reference materials. Experiences similar to ours were occurring throughout Saudi Arabia. Army pharmacy had been challenged. The challenge was accepted, and viewed as an opportunity to excel, by providing the best possible pharmaceutical care to conserve the fighting strength of our armed forces. PMID- 8441507 TI - A comparison of clinical diagnoses among male and female soldiers deployed during the Persian Gulf War. AB - A comparison of medical disorders between male and female soldiers during Operations Desert Shield and Desert Storm is presented. Acute gastrointestinal, acute respiratory, dermatologic, dental, psychiatric, orthopedic and optometric disorders were chosen for study. No association between the groups was noted for acute minor illnesses and dental disorders. Men were more likely to be diagnosed with orthopedic and dermatologic disorders (p < 0.001 and p < 0.019). Women were more likely to be diagnosed with psychiatric and optometric disorders (p < 0.001 and p < 0.001). These results can assist military and medical strategists target differential health care to male and female soldiers in the deployed garrison and combat scenarios. PMID- 8441508 TI - Ethnicity and child dental health status in the Manawatu-Wanganui Area Health Board. AB - Dental caries data on 3,283 5-year-old children, taken at the completion of their first treatment in the School Dental Service as new school entrants, showed that non-Maori children were three times more likely than Maori children to have no experience of caries. Maori children were three times more likely to have high (five or more missing or filled teeth) caries experience than non-Maori children. Caries experience in Pacific Island children lay between the Maori and non-Maori children. Maori children were almost three times more likely to have had general anaesthesia for dental treatment than were non-Maori. From records of 3,329 Form II (aged 12 or 13) children taken at the conclusion of their last treatment in the School Dental Service, non-Maori children were found to be twice as likely than Maori to have had no experience of caries. Maori children were over twice as likely to have had high (five or more missing or filled permanent teeth) caries experience than non-Maori. It is unlikely that the dental health outcome differences between Maori and non-Maori children will be reduced by the current dental health care system unless dental health promotion becomes more effective and culturally appropriate. PMID- 8441509 TI - Te niho waiora me te iwi Maori: dental health and the Maori people. AB - The standard of dental health for Maori people is still far below that of the non Maori (Pakeha or European) in this country. Their dental health needs are not being met by the dental profession. However, by making the delivery of dentistry culturally acceptable to Maori people and making dentistry appropriate and accessible for Maori people, much can be achieved. The Maori Dental Health Clinic at the School of Dentistry has shown this in the short time of its existence. One cannot change the way in which a restoration is done, but one can change the approach in which that restoration is done. By acknowledging and recognising the importance of the whanau, the family, in the delivery of dental health services, the dental profession in this country can go a long way to improve the dental health of the Maori people. Kia ora koutou katoa. PMID- 8441510 TI - Evaluation of a 10 percent carbamide peroxide gel vital bleaching agent. AB - A clinical study determined the whitening effect of a 10 percent carbamide peroxide gel on the teeth of 10 subjects. Histological evaluation of the effect of this agent on human tooth pulps and hamster cheek pouch tissues was also undertaken. The gel provided a modest, but unpredictable, whitening of discoloured teeth. A localised mild to moderate inflammatory response was found in some of the pulps of teeth that had been bleached. No soft-tissue changes were observed in the hamster cheek pouches. PMID- 8441511 TI - Prevention of infective endocarditis. PMID- 8441512 TI - Molar endodontics. AB - Molar endodontics is an extensive and complex subject. The treatment of molar teeth has deservedly taken a position of elevated importance in recent years. No longer are the molar teeth a target for extraction forceps, but are more often nowadays a target for crowns. Patients and dentists alike are striving to keep the marvellous molars and, with this in mind, the pillars of the future crowns and bridges must be preserved. Endodontic treatment of molar teeth is basically no different from treating the simple, single, straight canal. The principles of complete debridement, obturation and restoration are the same. The stumbling blocks confront us in the way of anatomical variations, difficulty with isolation and access and, probably the simplest and most crucial factor, time. Given the devotion of enough time, patience, and practice, the desired result will be achievable. PMID- 8441513 TI - What is hospital dentistry? PMID- 8441514 TI - Continuing professional development. AB - There is increasing political and consumer pressure on professions, which have a degree of monopoly of service, to ensure that their members are competent to practise. One means of maintaining competence is the requirement of professionals to undertake professional development activities throughout their practising careers. Options reviewed are: voluntary attendance at continuing education activities; complaints-initiated professional development; compulsory attendance at continuing education activities; practice audit; a professional development programme for recent graduates; and the professional development review process. PMID- 8441515 TI - Splenic artery aneurysm rupture during pregnancy. AB - Rupture of a splenic artery aneurysm during pregnancy or delivery is an unusual event. Only 98 previous cases have been reported. The survival of both mother and fetus is even more uncommon. This paper describes the tenth case of maternal fetal survival after splenic artery aneurysm rupture. The literature is reviewed in detail with emphasis on the epidemiology, etiology, clinical presentation, and treatment of this problem. A high index of suspicion and an awareness of the management options are necessary to achieve a successful outcome. PMID- 8441516 TI - Coccidioidomycosis and pregnancy. AB - Pregnant women with respiratory symptoms of pleuritic pain and productive cough should undergo evaluation for coccidioidomycosis. This should include a history of travel or residency in endemic areas and careful assessment for toxic erythema, erythema nodosum, or erythema multiforme. To confirm a diagnosis of this disease, a sputum culture, wet mount, and serological tests should be performed. The risk of dissemination, which is highest in the second and third trimesters, can be estimated by a complement-fixation titer. In disseminated cases aggressive treatment with amphotericin B has improved the previously reported high maternal and neonatal mortality rate. Fortunately, case reports do not indicate that transplacental spread occurs. Reactivation or exacerbation of a chronic low-grade infection during pregnancy may occur in patients treated for prior disseminated disease (32, 34). Interestingly, both of the reported cases of reactivation or exacerbation occurred in insulin-dependent diabetics. PMID- 8441517 TI - Cell potential of isolated outer hair cells as a function of extracellular K+ concentration. AB - Outer hair cells were isolated from apical turns of the guinea pig cochlea. The membrane potential differences of cells in extracellular medium with 5.8, 14.0, 28.9 or 67.5 mmol/l of potassium were -72.0 +/- 0.6 (mean +/- SEM, n = 93), -50.1 +/- 2.1 (n = 4), -37.7 +/- 0.5 (n = 73) or -20.0 +/- 1.5 mV (n = 16), respectively. Membrane depolarization can explain two thirds of the K(+)-induced shortening of isolated outer hair cells. PMID- 8441518 TI - Immunohistochemical localization of carbonic anhydrase in the endolymphatic sac of the mouse and guinea pig. AB - The localization of carbonic anhydrase (CA) in mouse and guinea pig endolymphatic sac (ES) was determined by immunohistochemistry. In the distal and intermediate portions of the ES of both species, epithelial cells reacted with anti-CA antiserum. All epithelial cells in the distal portion stained for CA. In the intermediate portion, immunoreactivity was prominent in about half the epithelial cells, but less intense in the remaining epithelial cells. The proximal portion of the ES lacked immunoreactivity. CA may play a crucial role in ES electrolyte transport. PMID- 8441519 TI - Ultrastructure of nerve endings in the stapedius muscle of the squirrel monkey. AB - The stapedius muscle of the squirrel monkey (Saimiri sciureus) was studied electron microscopically with regard to neuromuscular junctions, muscle-tendon junctions and tendons. Two types of neuromuscular junctions were identified. The first type which was predominant in number showed well-developed primary and secondary synaptic clefts. They were almost the same with those of other mammalian skeletal muscles. The second type showed a flat-shaped junction with fewer secondary synaptic clefts. Muscle-tendon junctions were characterized by many interdigitations between the muscle fibers and tendon. The tendon was composed of collagen fibers, approximately 70-100 nm in diameter. Muscle spindles were not present, while nerve endings resembling the Golgi tendon organ were found adjacent to the tendon and the muscle-tendon junctions. These findings suggest that a feedback system may exist and regulate the fine contractile function of this muscle. PMID- 8441520 TI - Steroid-responsive sensorineural hearing loss: combination therapy with prednisolone and Sairei-to. AB - We observed cases of hearing loss in which hearing deteriorated when steroid therapy was discontinued and improved upon re-administration. We identified these as cases of steroid-responsive sensorineural hearing loss (SNHL). The diagnostic criteria for determining steroid-responsive SNHL were stated, and 10 cases were examined. The 10 cases of steroid-responsive SNHL were divided into two groups: 3 cases associated with aortitis syndrome (systemic type) and 7 cases with no known systemic disease (localized type). Relatively satisfactory hearing was maintained in these cases by long-term oral administration of prednisolone (PSL). The combined use of Sairei-to made it possible to decrease the necessary maintenance dose of PSL. While the pathology of steroid-responsive SNHL is still unclear, it is suspected that immune complex disease or vasculitis may be involved. PMID- 8441521 TI - The so-called 'allergic' nasal polyp. AB - A series of 95 consecutive patients who have had a polypectomy was investigated with regard to clinical history and the morphology of the polyps. The results were compared with a series of 203 patients with allergy, of whom 12 had been polypectomized. The study revealed that a high percentage of the 95 patients had subjective complaints, particularly nasal congestion, nasal discharge, sneezing, headache, snoring and a loss of smell. The latter was present in nearly 58% of the patients, and persisted long after the operation in a third of the cases. More than 50% of the 95 patients had had 3 or more polypectomies. Rather few patients suffered from allergy-like conditions. Eighty-two of the 95 polyps were of the ordinary, oedematous, eosinophilic type; 7 were neutrophilic, fibro inflammatory; 5 showed pronounced hyperplasia of the seromucinous glands, and 1 was a so-called polyp with atypical stroma. Only 6% of the 203 patients with allergy had had a polypectomy. Ten of the 12 polyps removed from the series of patients with allergy were of the ordinary type and 2 of the fibro-inflammatory type. A review of the literature is done concerning the association between nasal polyp and different diseases. The results of the present study support the concept that allergy is not the only cause for nasal polyps and that the accumulation of eosinophilic granulocytes observed in most polyps is often not related to allergy. PMID- 8441522 TI - Nitrogen dioxide-induced eosinophilia and mucosal injury in the trachea of the guinea pig. AB - Nitrogen dioxide exposure-induced mucosal pathology of the guinea pig trachea was studied. Exposure to 3 or 9 ppm of nitrogen dioxide for 6 h a day, 6 times weekly for 2 weeks resulted in decreased ciliary activity as well as a dramatic eosinophil accumulation to the epithelium and submucosal layer. Especially exposure to 9 ppm of nitrogen dioxide induced epithelial injury through the activation of eosinophils accumulated in the tracheal mucosa. The epithelial damage induced by nitrogen dioxide could lead to hyperresponsiveness and prolonged allergic inflammation. Our study suggests that environmental nitrogen dioxide could contribute to the hyperresponsiveness and could most probably be involved in the development and chronicity of airway allergic disorders. PMID- 8441523 TI - Fine-needle aspiration in the diagnosis of head and neck growths: the pitfalls of false-positive diagnosis. AB - The results of fine-needle aspiration cytology (FNA) performed on 235 patients with head and neck growths were analyzed. The accuracy rate was 83%. The FNA was nondiagnostic in 9%, false negative in 7% and false positive in 1% of the cases. These results are similar to those in other centers. Due to false-negative diagnoses, FNA rarely allows the making of a major clinical decision. False positive diagnoses oblige the clinician to perform several investigations to assess the diagnosis of nonmalignancy and to reassure the patient. Thus, in our opinion, FNA is helpful for the diagnosis of head and neck growths in some rare situations only. PMID- 8441525 TI - Dumbbell-shaped schwannoma of the jugular foramen. AB - A 49-year-old male patient with schwannoma of the jugular foramen is described. T1-weighted magnetic resonance imaging with gadolinium showed an enhanced dumbbell-shaped mass with its smaller part occupying the left cerebellopontine angle and its larger part in left parapharyngeal space. The mass was totally removed with a left mastoidectomy and suboccipital craniotomy. The dura mater was closed with anterior lamina of the rectus sheath, and the large defect of the neck was obliterated with free rectus abdominis muscular flap. The postoperative course was uneventful, except for some sputum aspiration and hoarseness. He underwent surgical mediation and cricopharyngeal myotomy for his left, paralyzed vocal cord, and both speech and swallowing function improved quite well. This paper reports our experience in managing this dumbbell-shaped neurinoma of the jugular foramen. PMID- 8441524 TI - Unusual case of plasma cell tumor with monoclonal gammopathy of the sino-nasal cavity and clavicular bone. AB - A rare case of extramedullary plasmacytoma in the sino-nasal cavity is presented. During a prolonged clinical course, the tumor has recurred several times after irradiation, chemotherapy and surgery, and presented in the clavicular bone as well. Immunohistochemical staining of each tumor showed IgA kappa phenotype, and immunoelectrophoresis of the serum showed overproduction of IgA with kappa light chains. Although an elevation of serum IgA persists, the patient has remained well without evidence of overt multiple myeloma. PMID- 8441526 TI - Anterior communicating artery aneurysm presenting as pulsatile tinnitus. AB - Objective tinnitus is caused by a vascular abnormality of the cervical region, skull base or intracranium. These lesions produce an abnormal flow lesion in the arterial or venus circulatory system of the brain, skull base or cervical region. This flow abnormality is perceived by the auditory system as pulsatile tinnitus. An aberrant carotid artery, a dehiscent jugular bulb or a glomus tumor are common causes. The cause of subjective tinnitus is often not found. Many serious vascular anomalies and tumors can present as pulsatile tinnitus. These include: arteriovenous malformations, atherosclerotic vascular disease, and intracranial tumors with elevated cerebrospinal fluid pressure. We recently diagnosed a patient with an anterior communicating artery aneurysm presenting with pulsatile tinnitus. An aneurysm presenting as pulsatile tinnitus is extremely uncommon. Only 8 have been identified in the literature. The clinician evaluating patients with tinnitus must be aware of this diagnosis. A complete evaluation should include an appropriate radiologic exam; either computed tomography or magnetic reasonance imaging. PMID- 8441527 TI - Morphologic damage and changes of intracellular calcium-binding sites after acute noise trauma in the organ of Corti of the guinea pig. AB - In guinea pigs, an acute acoustic trauma was created by 6 consecutive gunshots. The sound pressure at the ear drum was 156 +/- 4 dB, the frequency maximum was between 4 and 6 kHz. Sixty hours after the noise trauma, the animals were decapitated, and the cochleae were prepared for microscopic analysis of the resulting trauma to the organ of Corti. During the process of fixation, the potassium-pyroantimonate precipitation reaction was performed to localize calcium binding sites. The pattern of cell morphology and the distribution of calcium binding sites was compared to that of normal control animals. Morphologic changes of the cells in the organ of Corti correlated with changes of the cellular calcium distribution, indicating the crucial role of calcium in cell damage and necrosis after acute noise trauma. PMID- 8441528 TI - [Hypertension and multimetabolic syndrome]. AB - The occurrence of multi-metabolic syndrome was studied by authors on 31 patients with obesity of android type and hypertension. Plasma glucose and plasma insulin levels were investigated during oral glucose tolerance test, plasma lipid levels were determined, furthermore body mass index and waist/hip ratio were calculated. It was considered that in 65 percent of the cases the presence of multi-metabolic syndrome could have been proved. Dyslipidemia in 22 cases, hyperinsulinemia in 20 cases, deterioration of the carbohydrate metabolism in 14 cases could be demonstrated. The negative correlation between glucose- and insulin-responses to glucose challenge may suggest the presence of insulin resistance. No significant difference was found in metabolic parameters between men and women. The multi metabolic syndrome is regarded by authors as a process which may lead to both type 2 diabetes mellitus and atherosclerosis. According to their appearance about two third of these patients could be screened. Authors emphasize the great significance of this problem and the importance of early diagnosis and prevention. PMID- 8441529 TI - [Effect of spinal exercises on spinal parameters in Scheuermann disease]. AB - Changes in the parameters of the spine (grade of kyphosis, total mobility of dorsolumbal spine, lumbal Schober's sign, finger-ground distance) within one year were studied in 103 Scheuermann-patients. In patients doing regular exercises the kyphosis did not increase and their finger-ground distance improved significantly; whilst in patients not doing regular exercises the kyphosis increased slightly though significantly, and their finger-ground distance did not improve. These result prove the beneficial effect of regular exercises. PMID- 8441530 TI - [Effect of antibiotics on autochtonous intestinal E. coli population in SPF mice and on planktonic phase isolates]. AB - Representatives of different groups of antibiotics were tested on the autochtonous Escherichia coli of mice being in biofilm mode of growth, as well as on their isolates in planktonic phase. Aminoglycoside antibiotics, chloramphenicol, oxytetracycline, erythromycin, lincomycin-clindamycin, and polymyxins showed a very reduced effectivity on Escherichia coli embedded in the biofilm matrix. On the other hand, beta-lactam antibiotics were equally effective both for sessile and planktonic bacteria. Derivates with broader, or broad spectra showed an increased biofilm activity. Testing the possibilities of penetration or concentration on mouse colonic pieces exposed to 2 Minimal Bactericidal Doses--polymyxin B showed no sign of penetration into the colonic mucus, while 2.9% of streptomycin and 60% of the exposed quantity of carbenicillin was detected in the intestinal mucus. Ampicillin, however, has concentrated about three-four times in the intestinal matrix. PMID- 8441531 TI - [Retroperitoneal Castleman tumor]. AB - Authors removed a 4 cm diameter tumour from below and behind of the hepatic hilum of a 40 y. o. woman. Histology revealed Castleman disease. 40 retroperitoneal Castleman tumour can be red in the literature, without any Hungarian one. The pathological and clinical characteristics of Castleman tumour are discussed, literature is surveyed. PMID- 8441532 TI - [Basic principles of the new health care financing system]. PMID- 8441533 TI - [Pushkin's family tree]. PMID- 8441534 TI - An external reference to identify the internal auditory canal in middle fossa surgery. AB - Traditional middle fossa landmarks, such as the facial hiatus and arcuate eminence, are often unreliable. This study was performed to establish an external reference from which to identify precisely the surgical anatomy of the middle fossa. The head of the malleus was identified from the middle fossa in the temporal bones of 20 adults. The lateral cortex of the temporal squamosa at the zygomatic root was used as the external plane of reference. The head of the malleus was consistently located 18 mm medial to the outer cortex on a line perpendicular to the reference plane. Medial extension of this line through the malleus head bisected the internal auditory canal. We recommend this method to precisely locate the malleus head as the first landmark in the middle fossa. Other structures, such as the geniculate ganglion, internal auditory canal, and superior semicircular canal can then be safely identified. We also present our results using this technique in six consecutive patients undergoing middle fossa surgery during the past 12 months. PMID- 8441535 TI - Obstructive sleep apnea syndrome: a review of 306 consecutively treated surgical patients. AB - Three hundred six consecutively treated surgical patients with obstructive sleep apnea syndrome were evaluated from a group of 415 patients. One hundred nine patients were excluded because they failed to obtain a postoperative polysomnogram or were lost to followup. All patients received a physical examination, cephalometric analysis, fiberoptic examination, and polysomnography before treatment to document OSAS and determine the areas of obstruction. A two phase surgical protocol was used for the reconstruction of the upper airway. Phase I surgery consisted of a uvulopalatopharyngoplasty (UPPP) for palatal obstruction and genioglossus advancement with hyoid myotomy-suspension for base of tongue obstruction. Failures of phase I were offered phase 2 reconstruction, which consisted of maxillary-mandibular advancement osteotomy. One hundred twenty one patients were treated with nasal continuous positive airway pressure (CPAP) before surgery and this was the primary method of evaluating surgical success. Results were reported on the polysomnogram performed a minimum of 6 months after surgery and compared to the preoperative polysomnogram and the second night nasal CPAP study. The polysomnographic results included respiratory disturbance index (RDI), lowest oxyhemoglobin saturation (LSAT), and sleep architecture parameters. Surgery was considered a success if it was equivalent to nasal CPAP or the postoperative RDI was less than 20 with normal oxygenation. The overall success rate, which included patients that dropped from the protocol, was 76.5%, with a mean followup of 9.3 months (SD, 6.7). The preoperative RDI, nasal CPAP RDI, and postoperative RDI were 55.8 (SD, 26.7), 7.2 (SD, 5.4), and 9.2 (SD, 7.5), respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441536 TI - Intraoperative facial nerve monitoring in posterior fossa acoustic neuroma surgery. AB - Intraoperative facial nerve monitoring has become an indispensable tool during cerebellopontine angle surgery. Ninety-seven patients underwent surgical removal of an acoustic neurinoma with the use of a pneumatic sensor monitoring between January 1, 1986, and December 31, 1990. In the early postoperative period, a normal or near-normal facial function (grades I and II) was achieved in 86% of the patients, a moderate dysfunction (grade III) was present in 7%, and a total or severe dysfunction (grades V or VI) was present in 6%. Normal function at 1 year was achieved in 90.5% of the patients, 4% were grade II, a moderate dysfunction (grade III) was present in 2%, and 3% showed a total or severe dysfunction (grade V and VI). The incidence of normal function decreased with tumor size, with an occurrence rate of 100%, 94%, and 91% in small, medium, and large tumors, respectively. In eight consecutive patients, all responses detected by the monitoring during the operation were collected and analyzed according to intraoperative events. Analysis of the results indicate that 95% of the 316 mechanically induced stimulations were of small or extremely small amplitude, and only 5% were of moderate amplitude. A medial-to-lateral strategy of dissection, preservation of the arachnoid veil over the facial nerve, a control by the monitoring of the amount of traction, and a more widespread use of sharp dissection were the major approaches to reduce surgical trauma during dissection. PMID- 8441537 TI - Crystalline preparation of botulinum toxin type A (Botox): degradation in potency with storage. AB - Laryngeal injection of botulinum toxin type A is currently the most effective method of treating spasmodic dysphonia. Botox, a crystalline preparation of botulinum toxin type A, is the only toxin approved for clinical use in the United States and is packaged in vials of 100 mouse units (MU). One MU corresponds to the calculated median lethal intraperitoneal dose (LD50) injected in mice. The logistic problems arising from the need for repeated injections of small amounts of Botox have been addressed by several investigators by refreezing unused Botox for use at a later time. Although FDA labeling recommends that Botox not used within 4 hours of reconstitution be discarded, data regarding degradation in potency after reconstitution and refreezing are not currently available. Using the LD50 Swiss-Webster mouse bioassay and statistical analysis by the Probit procedure, a 69.8% loss in potency was found when Botox was reconstituted, immediately frozen, and then assayed 2 weeks later (p < 0.0001). Statistically significant degradation in potency was seen after refrigerator storage for 12 hours (p = 0.007), but not for 6 hours (p = 0.16). Clinical implications regarding the dilution, use, and storage of Botox are discussed. PMID- 8441538 TI - Arterial supply of the human endolymphatic duct and sac. AB - The arterial anatomy of the endolymphatic duct and sac was studied in vascular casts of methyl methacrylate of six human heads. The chief source of arterial blood supply to the endolymphatic duct and sac appeared to be the occipital artery. Arterioles entered the bone of the mastoid process. Arterioles in bone, the walls of the sigmoid sinus, and the posterior fossa dura coursed medially to supply the endolymphatic sac. The orientation of arterioles tended to be along the long axis of the endolymphatic duct and sac, whereas venules were more likely to be circumferentially oriented. Arterioles arising from dural vessels divided into deeper branches, which supplied periductal connective tissue, and superficial branches, which entered canaliculi of the vestibular aqueduct. Gross anatomic findings were confirmed by histologic examination of temporal bones. PMID- 8441539 TI - Prolongation of secondary critical ischemia time of experimental skin flaps using UW solution as a normothermic perfusate. AB - A myriad of investigations have been published on the pharmacologic manipulation of flaps to enhance tolerance to ischemia. We recently reported a threefold increase in ischemic tolerance of the rat abdominal skin flap pedicle after 6 hours of primary ischemia and 12 hours of reperfusion. Flaps underwent normothermic perfusion washout with lactated Ringer's or U.W. solution, a newly developed organ preservation medium. Perfusion washouts were performed at one of three different points in the protocol: (1) onset of primary ischemia; (2) onset of secondary ischemia; or (3) 2 hours after onset of secondary ischemia. The last group was used to simulate the clinical situation in which flaps are discovered and salvage procedures instituted at a delayed time interval. This is the longest normothermic ischemic interval reported. We undertook the present study to determine the utility of the U.W solution in prolonging the tolerance of the flap to a second ischemic insult after a period of reperfusion. Seventy-five unilateral rat abdominal skin flaps were raised. Secondary ischemia was produced by placing a microvascular clamp across the inferior epigastric pedicle. Flap survival was assessed at 1 week postoperatively. While none of the nonperfused flaps survived 8 hours of secondary ischemia, at least 50% of the U.W. perfused flaps survived an average of 14 hours of secondary ischemia. Lactated Ringer's perfusion washout only modestly increased the ischemic tolerance. Perfusion washout in the secondary ischemic phase improved the ischemic tolerance to a significantly greater degree than in the primary ischemic interval. PMID- 8441540 TI - Madelung's disease: case reports and literature review. PMID- 8441541 TI - Prevertebral space infections associated with cervical osteomyelitis. PMID- 8441542 TI - Aspergillus mastoiditis. PMID- 8441543 TI - Guillain-Barre syndrome presenting as acute bilateral vocal cord paralysis. PMID- 8441544 TI - Cochlear implantation in the congenitally malformed ear. AB - A child with a congenital hearing loss and auricular malformations was evaluated for cochlear implantation. Preoperative radiologic studies demonstrated a common cavity cochlear malformation and a contralateral narrow internal auditory canal. Intraoperative findings included an aberrantly coursing facial nerve, preventing routine placement of the electrode array. The surgical approach was consequently modified and the cochlea was accessed through a malformed semicircular canal. Cochlear implantation can be performed safely and effectively in children with congenitally malformed ears. PMID- 8441545 TI - Infiltrative clival pituitary adenoma of ectopic origin. AB - An ectopic pituitary adenoma is a rare entity that may occur in several anatomic locations, the sphenoid sinus being the most common. Many of these tumors are amenable to surgical resection by means of a transsphenoidal approach. A more aggressive surgical approach is needed to attempt resection of extensive tumors that involve the clivus and the nasopharynx. Complete resection in these areas cannot always be guaranteed or determined, necessitating postoperative radiotherapy. Many different tumors of the sphenoid sinus and skull base can resemble ectopic pituitary adenomas on radiologic assessments. Because of this, preoperative endocrine assessment is recommended. PMID- 8441546 TI - Leiomyosarcoma of the trachea. PMID- 8441547 TI - Enteric duplications of the mouth. PMID- 8441548 TI - Chylous cyst of the neck in an adult. PMID- 8441549 TI - Spontaneous posterior fossa cerebrospinal fluid leak. PMID- 8441550 TI - Custom septal button. PMID- 8441551 TI - Suspension platform for stable microlaryngoscopy. PMID- 8441552 TI - Prosthetic restoration of the paralyzed face. PMID- 8441553 TI - Heterotopic gastric mucosal cyst of the tongue. PMID- 8441554 TI - National survey of neonatal transfusion practices: I. Red blood cell therapy. AB - Neonatal blood component transfusion practices during 1989 were surveyed via a questionnaire developed by the Pediatric Hemotherapy Committee of the American Association of Blood Banks. Of 1790 questionnaires mailed, 452 were selected to form the database for this analysis because they were from institutions in which neonates were transfused. Nearly all institutions contained intensive care units directed by neonatologists and were involved in the management of high-risk infants. Results from institutions serving as the primary pediatric teaching hospital of a medical school were compared with those with no medical school affiliation. Thirty-six percent of primary pediatric teaching hospitals and 52% of hospitals with no medical school affiliation performed pretransfusion testing in excess of that required, resulting in additional blood loss in neonates. Sixty six percent of primary pediatric teaching hospitals used fresh frozen plasma to adjust the hematocrit of red blood cell concentrates prior to transfusion (a practice increasing donor exposure), compared with only 29% of hospitals with no medical school affiliation. The usual indication for small-volume red blood cell transfusions in severely ill neonates was to maintain a desired hematocrit level, whereas for stable infants, red blood cell transfusions were given to treat symptomatic anemia, rather than to maintain a predetermined hematocrit. As found in 1985, neonatal transfusion practices in 1989 were variable. However, improvements have occurred since 1985 to suggest that further research and educational efforts may serve to promote even better neonatal transfusion therapy. PMID- 8441555 TI - Prolonged clinical use of a heme oxygenase inhibitor: hematological evidence for an inducible but reversible iron-deficiency state. AB - The heme oxygenase inhibitor tin (Sn4+)-mesoporphyrin, administered to two 17 year-old Crigler-Najjar type I patients during a 400-day study to lower plasma bilirubin levels, also produced changes, beginning approximately 50 days after initiation of treatment, in hematological and iron metabolism indices consistent with the development of iron deficiency anemia. These indices were responsive to iron supplementation and reverted to normal after termination of inhibitor treatment. Tin-mesoporphyrin enhances biliary heme excretion and inhibits intestinal heme oxygenase when administered orally or parenterally; the changes in blood indices could thus reflect, in part, blockade of heme catabolism and therefore of uptake of heme-derived iron, by intestinal epithelium. This action of the inhibitor suggests that such agents may facilitate studies involving aberrant metabolism of heme-derived iron in humans and that they merit further investigation with respect to their potential value in enhancing iron disposal in certain disorders such as those related, for example, to transfusion-induced iron overload states. PMID- 8441556 TI - The Vermont-Oxford Trials Network: very low birth weight outcomes for 1990. Investigators of the Vermont-Oxford Trials Network Database Project. AB - This report describes the Vermont-Oxford Trials Network, a voluntary collaborative research network, and summarizes the outcomes and medical interventions for very low birth weight infants at participating centers in 1990. The Vermont-Oxford Trials Network included 36 centers in 1990 (11% university hospitals, 44% university affiliates, 44% nonaffiliated) with a total of 2961 infants weighing 501 to 1500 g (median 73 infants, range 5 to 172). Eighty percent of the infants were inborn and 65% were white. The overall network frequencies for selected interventions and outcomes were as follows: prenatal care, 90%; a complete course of antenatal corticosteroids, 12%; cesarean section, 56%; surfactant therapy, 49%; postnatal steroids for chronic lung disease, 16%; high-frequency ventilation, 4%; patent ductus arteriosus, 31%; necrotizing enterocolitis, 6%; bacterial sepsis, 16%; and intraventricular hemorrhage, 26%. By 28 days, 15% of the infants had died and 8% had been transferred, whereas by discharge 18% had died and 18% had been transferred. There were marked variations among the centers in the frequencies of different medical interventions and in the frequencies of various clinical outcomes. The Vermont-Oxford Trials Network is a unique collaborative research group composed of a broad range of neonatal intensive care units. During 1990 there were considerable differences among the centers in the interventions used and patient outcomes observed. The investigators plan to devote the resources of the Network to a research program of randomized trials and outcome studies so that effective interventions can be identified and the quality of neonatal intensive care can be continuously improved. PMID- 8441557 TI - Treatment Investigational New Drug experience with Survanta (beractant). AB - From September 1989 through July 1991, before commercial availability, Survanta (beractant intratracheal suspension), a modified bovine-derived surfactant used for prevention and treatment of neonatal respiratory distress syndrome, was made available to 231 neonatal intensive care units in the United States and Canada under a Treatment Investigational New Drug protocol. Results of this open clinical experience are reported. Investigators could give one dose of Survanta soon after birth to neonates weighing 600 to 1250 g (prevention strategy). Neonates weighing 600 to 1750 g who were not treated at birth could begin Survanta therapy if respiratory distress syndrome developed within 8 hours of birth (rescue strategy). All neonates could receive up to three more doses over the first 48 hours of life at minimum intervals of 6 hours if they met retreatment criteria. Qualifications for enrollment closely matched those used in previous randomized controlled clinical trials. This report includes results from 8168 neonates who completed the study. Treatment Investigational New Drug rates for intracranial hemorrhage, patent ductus arteriosus, pulmonary hemorrhage, pulmonary air leaks, bronchopulmonary dysplasia, death or bronchopulmonary dysplasia, pulmonary interstitial emphysema, pretreatment sepsis, and posttreatment sepsis were less than for treated neonates in the controlled trials and survival was equivalent across studies. Problems with treatment administration were reported with 30.4% of doses, while adverse events were reported in 0.5% of neonates. The results of the Treatment Investigational New Drug protocol revealed no new safety concerns associated with the widespread use of Survanta and confirmed the safety profile established in earlier controlled trials. PMID- 8441558 TI - Association between neonatal care practices and efficacy of exogenous human surfactant: results of a bicenter randomized trial. AB - The purpose of this study was to analyze the impact of neonatal care practices on the efficacy of exogenous human surfactant. Two hundred newborns (gestational age 24.0 to 29.9 weeks, lecithin-sphingomyelin ratio less than 2 or absent phosphatidylglycerol, and requirement of mechanical ventilation at birth) participated in a randomized bicenter trial of human surfactant substitution. In only one of the two sites (site 2) surfactant substitution decreased the severity of respiratory failure and increased neonatal survival without bronchopulmonary dysplasia. For analysis of three-way association, continuous variables describing patient characteristics and treatment were dichotomized at the median. The following variables were significantly associated with good outcome in site 1 and 2 and with surfactant substitution in site 2: low oxygen requirement during first three neonatal days, low mean airway pressure during second and third day, low PaCO2 during first two neonatal days, and no ligation of ductus arteriosus. Low fluid intake during the first three days and low colloid intake during the first two days of life were associated with good outcome in both sites. The ratio between mean airway pressure and the oxygen requirement was higher in site 2 than in site 1 during the first day of life. Fluid intake and ventilatory management may influence the efficacy of exogenous surfactant. PMID- 8441559 TI - Adolescent abortion: views of the membership of the American Academy of Pediatrics. AB - To identify the positions held by the American Academy of Pediatrics (AAP) membership on a number of issues that may be topics of legislation regarding abortion, the AAP carried out a survey based on a random sample of 1000 active US members. A total of 785 usable questionnaires were returned. The majority of members surveyed (56.7%) favored access to abortion for adolescents for all the reasons identified in the questionnaire; 35.4% believed abortion should clearly be restricted in some circumstances, and 7.0% believed adolescents should not have access to abortion under any circumstances. For each individual reason for abortion, at least 60% of the membership believed adolescents should have access to abortion services. In addition, most pediatricians supported legal positions that would facilitate access to abortion services for adolescents. Urban, female, and non-self-employed pediatricians were slightly more likely to support access to abortion by adolescents than comparison groups. Discussion focuses on the extent to which pediatricians' views reflect medical concerns, the extent to which their views are reflected in the current laws, and implications for practice and for AAP policy. PMID- 8441560 TI - Psychological sequelae of medical complications during pregnancy. AB - To determine whether mothers with complicated pregnancies are at increased risk of postpartum depression and whether their children are at increased risk of being perceived as vulnerable, the investigators conducted an interview survey of mothers of 1095 children aged 4 to 8 in a community-based sample of primary care pediatric practices. The offspring were viewed as vulnerable by 17% of the women with severe pregnancy complications and 9% of the women without pregnancy complications (relative risk = 1.88; 95% confidence interval = 1.11, 2.63). Women with a severe complication of pregnancy were significantly more likely to report postpartum depression than those without a complication (27% vs 11%; relative risk = 2.45; 95% confidence interval = 1.55, 3.01). These relationships persisted after adjustment for prematurity, neonatal hospitalization, and demographic factors. It is concluded that pregnancy complications may place a woman at increased risk of postpartum depression and may have important effects on a mother's long-term perceptions of her child's vulnerability to illness. PMID- 8441561 TI - Effect of maternal race on outcome of preterm infants in the military. AB - Previous studies suggest that low birth weight black infants have less morbidity and birth-weight-specific mortality during the perinatal period than low birth weight white infants. We studied the effect of maternal race on outcome in preterm infants born at a military hospital that offers free access to obstetric and neonatal care. Between January 1, 1986, and December 31, 1991, data were prospectively collected on all 667 infants delivered at Wilford Hall USAF Medical Center with an estimated gestational age of less than 35 weeks. Three hundred ninety-two white infants and 165 black infants were included in the data analysis. The mean (+/- SD) birth weight was 1701 +/- 65 g for white infants and 1462 +/- 66 g for black infants. The mean estimated gestational age was 31.0 +/- 3.2 weeks for white infants and 29.9 +/- 3.8 weeks for black infants. Preeclampsia was more frequent in black mothers than in white mothers for the entire study population (21% vs 14%), but the birth weight differential between races remained after correction for preeclampsia. There were no significant differences between races in stillbirths, gender, maternal age, maternal transfer status, number of prenatal visits, or percentages of mothers with small-for gestational-age infants, multiple-gestation infants, prolonged rupture of membranes, or initial prenatal visit during the first trimester. Intraventricular hemorrhage was more frequent in white infants at 27 through 29 weeks estimated gestational age (50% vs 13%). There were no significant differences between the two groups in survival or in the occurrence of severe intraventricular hemorrhage or bronchopulmonary dysplasia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441562 TI - Are there good ways to give 'bad news'? AB - There has been considerable speculation about the inevitability of parental dissatisfaction with being informed about their child's disability. Mothers and fathers of 24 infants with a recently diagnosed disability were interviewed regarding their preferences for how to be told the "bad news." Qualitative analyses revealed nine themes of parental preferences for how to communicate difficult information. Parents affirmed communication themes previously discussed in the literature, such as being told early and together, and identified new ones, such as affective tone and physical contact with their baby. The importance of these themes is presented for this sample. Recommendations for how to present "bad news" can be concisely drawn from these findings. Results suggest that parental dissatisfaction with the process of telling is not inevitable. PMID- 8441563 TI - Recent improvement in outcome using transcatheter embolization techniques for neonatal aneurysmal malformations of the vein of Galen. AB - Vein of Galen malformations may present as congestive heart failure in the neonate and are usually fatal if untreated. Early studies using transcatheter embolization techniques, in a series of 22 patients, had a 50% mortality rate and a 37% incidence of severe mental retardation in survivors. Modifications of embolization techniques and neonatal care have improved the outlook in a more recent series of 11 patients. The diagnosis was established within 3 days of life in 91% of the cases. No mortality occurred, and 6 of the patients were functionally normal at up to 30 months' follow-up. Although two patients had severe neurologic deficits and/or a seizure disorder, only one case was possibly temporally associated with the embolization procedure. Some developmental delay was noted in one other patient. These improvements result, in part, from modifications of the treatment protocol, including earlier diagnosis, avoidance of digoxin, improvement in the application of newer microcatheters and acrylic polymers (n-butylcyanoacrylate), avoidance of overly aggressive neurosurgical procedures, and the use of stable central vascular access for total parenteral nutrition accompanying other general improvements in neonatal care. PMID- 8441564 TI - Pediatric emergency medicine: state of the art. AB - To assess the current practice of pediatric emergency care in the United States, a questionnaire was mailed to the directors of all 240 emergency departments (EDs) affiliated with pediatric residency training programs in the United States. One hundred seventy-two programs (72%) returned completed surveys, which comprised 32 questions highlighting staffing patterns, ancillary services, clinical issues, and resident education. The mean annual ED census was 39,290; the mean number of visits for children 0 to 18 years of age was 17,473. Seven percent of pediatric visits were categorized as critical, 23% as urgent, and 70% as nonurgent. Eleven percent of patients were admitted to the hospital. During peak periods, patients whose visits were triaged as nonurgent waited an average of 1.5 hours to be seen by a physician. Twenty-eight percent of programs provided 24-hour on-site coverage by a pediatric attending physician or fellow. Of the remaining programs, the average daily on-site pediatric coverage was 8.6 +/- 6.2 hours. Eighteen percent of programs used physician assistants or nurse practitioners in the ED. During their first, second, and third years of training, pediatric residents spent an average of 5.2, 5.8, and 3.5 weeks in the ED, respectively. The majority of EDs handled all levels of pediatric trauma (84%), had dedicated trauma teams (73%), employed social workers specifically assigned to the ED (62%), and had child abuse teams (72%). Ninety-one percent of EDs had radio communications with prehospital care vehicles and 67% provided medical command for incoming pediatric patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441565 TI - Site of upper airway obstruction in infants following an acute life-threatening event. AB - Twenty-five patients were screened following an acute life-threatening event for the presence of obstructive and mixed apnea. Simultaneous cardiorespiratory monitoring with fiberoptic laryngoscopy was performed to identify the site of upper airway obstruction during these episodes. In 3 of these subjects, who had been born prematurely, obstruction was observed at the laryngeal level, with the arytenoid masses and aryepiglottic folds closing over across the vocal cords. Such closure was also observed during periodic breathing, which was found to be prominent in 4 of the infants studied. The possible role of laryngeal reflexes as a mechanism for these events is discussed. PMID- 8441566 TI - Arterial partial pressure of oxygen required to achieve 90% saturation of hemoglobin in very low birth weight newborns. AB - Since very low birth weight preterm newborns are prone to oxygen toxicity and have red blood cells that have a high oxygen affinity, the knowledge of the P90 (the PaO2 required for 90% saturation of hemoglobin) could result in a more optimal oxygenation. This information could diminish the incidence of bronchopulmonary dysplasia and retrolental fibroplasia. To determine P90 and P50 (the PaO2 required for 50% saturation of hemoglobin), cord blood was obtained from 10 preterm newborns who were of less than 30 weeks' gestation (26.4 +/- 1.4 [SD] weeks) weighing less than 1000 g (816 +/- 119 g). The P50 and P90 were determined by gas mixing tonometry and expressed in millimeters of mercury at a temperature of 37 degrees C, a pH of 7.40, and PCO2 of 40 mm Hg. The tonometer permitted an equilibration and sampling of successive aliquots of blood at different oxygen tensions. Measurement of oxygen saturation, pH, and PaO2 provided the information for plotting the oxygen dissociation curve, the P50 and P90. There were at least six experimental points for each oxygen dissociation curve. The results showed that the mean P50 was 18.3 +/- 1.9 mm Hg (2.5 +/- 0.3 kPa) and the P90 was 40.8 +/- 3.6 mm Hg (5.4 +/- 0.5 kPa). This study demonstrates the fetal nature of the oxygen dissociation curve of very low birth weight newborns; but most importantly it also shows that when treating very low birth weight newborns with oxygen, a PaO2 of 41 mm Hg (5.5 kPa) is enough to saturate 90% of the hemoglobin at a physiological pH. This information could be of clinical importance to minimize oxygen toxicity. PMID- 8441567 TI - Is an emergency department visit a marker for undervaccination and missed vaccination opportunities among children who have access to primary care? AB - The purpose of this study was to determine: (1) whether preschool-age patients who utilize the emergency department (ED) are undervaccinated compared with patients having the same primary care provider and (2) whether reducing missed vaccination opportunities in the primary care office can potentially reduce the differences in undervaccination between the groups. This retrospective cohort study involved two groups: 583 ED patients, aged 4 to 48 months, who had primary care providers; and 583 control subjects randomly selected from primary care sites and matched according to date of birth and primary care site. The major outcome variable was the point prevalence of undervaccination, defined as more than 60 days past due for a vaccine at the time of the ED visit, and for control subjects, at the time of their matched patient's ED visit. Demographic variables, vaccination history, presence of chronic illness, and office utilization history were abstracted from office charts. The mean age of all patients was 20.0 months. Emergency department patients were more likely to be boys (61% vs 50%) and had more chronic illness, but did not differ racially from those in the control group. Primary care sites included a hospital-based clinic (n = 137), neighborhood health centers (n = 172), and private practices (n = 274). The undervaccination rates by primary provider type were for (1) hospital clinic ED patients 21.1%, control subjects 19.7%; (2) neighborhood health center ED patients 29.1%, control subjects 22.7%; and (3) private practice ED patients 26.6%, control subjects 14.9%. Overall, the odds ratio of ED patients' being undervaccinated compared with control subjects was 1.8 (95% confidence interval 1.3 to 2.5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441568 TI - Epilepsy as a risk factor for submersion injury in children. AB - The purpose of this study was to determine the risk of submersion injury and drowning among children with epilepsy and to define further specific risk factors. In a population-based retrospective cohort study the authors identified and reviewed records of all 0-through 19-year-old residents of King County, Washington, who suffered a submersion incident between 1974 and 1990. Children with epilepsy were compared with those without epilepsy with regard to age, sex, site of incident, supervision, outcome, and presence of preexisting handicap. Relative risks were determined using population-based estimates of epilepsy prevalence. Of 336 submersions, 21 (6%) occurred among children with epilepsy. Children with epilepsy were more likely to be greater than 5 years old (86% vs 47%) and more likely to submerge in a bathtub (38% vs 11%). The relative risk of submersion for children with epilepsy was 47 (95% confidence interval [CI] 22 to 100) in the bathtub and 18.7 (95% CI 9.8 to 35.6) in the pool. The relative risk of drowning for children with epilepsy was 96 (95% CI 33 to 275) in the bathtub and 23.4 (95% CI 7.1 to 77.1) in the pool. These data support an increased risk of submersion and drowning among children with epilepsy. PMID- 8441569 TI - Score for Neonatal Acute Physiology: a physiologic severity index for neonatal intensive care. AB - The substantial variation in birth weight-adjusted mortality among neonatal intensive care units (NICUs) may reflect differences in population illness severity. Development of an illness severity measure is essential for comparisons of outcomes. The Score for Neonatal Acute Physiology (SNAP) was developed and validated prospectively on 1643 admissions (114 deaths) in three NICUs. SNAP scores the worst physiologic derangements in each organ system in the first 24 hours. SNAP showed little correlation with birth weight and was highly predictive of neonatal mortality even within narrow birth weight strata. It was capable of separating patients into groups with 2 to 20 times higher mortality risk. It also correlated highly with other indicators of severity including nursing workload (r = .59), therapeutic intensity (r = .78), physician estimates of mortality risk (r = .65), and length of stay (R2 = .59). SNAP is an important new tool for NICU research. PMID- 8441570 TI - Efficacy of intranasal midazolam in facilitating suturing of lacerations in preschool children in the emergency department. AB - Sedating children safely and effectively for minor laceration repair is a well recognized clinical problem. A randomized, double-blind, and controlled study was conducted to evaluate the efficacy of intranasal midazolam for reducing stress during the suturing of lacerations in preschool children. Fifty-nine children with simple lacerations that required suturing were randomly assigned to one of three groups. Group 1 received intranasal midazolam, 0.4 mg/kg, prior to suturing. Group 2 received an equivalent volume of normal saline intranasally prior to suturing as a placebo. Group 3 was the control group and received no intervention prior to suturing. Heart rate, respiratory rate, blood pressure, and pulse oximetry were monitored at 5-minute intervals throughout the procedure. Subjective variables were also measured at 5-minute intervals and included a cry score, a motion score, and a struggle score. Parent satisfaction was measured via a short telephone interview the following day. There were no significant differences in outcome between the placebo group and the control group. Their results were pooled and compared with the results for the midazolam group. The midazolam group showed significant reductions for mean heart rate, maximum heart rate, and maximum systolic blood pressure when compared with the placebo/control group. Scores for two of the three subjective variables, cry and struggle, were significantly reduced for the midazolam group. The papoose board was considered unnecessary in retrospect for more than half of patients in the midazolam group compared with only one fifth of patients in the placebo/control group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441571 TI - From the bedside to the public policy arena: the role of general pediatric research. PMID- 8441572 TI - Comparison of stool containment in cloth and single-use diapers using a simulated infant feces. AB - Single-use diapers and cloth diapers with vinyl pants were compared for their relative abilities to contain stool within the diaper. Artificial feces with carbon black as an additive allowed a quantitative measure of fecal containment by image analysis in 60 infants. This method showed complete containment of feces in the diaper in 50% of the single-use diapers whereas only 10% of the cloth diapers showed complete containment. In infants where the border of the vinyl pants was used as the boundary of containment with the cloth diapers, complete containment occurred only 33% of the time. Fluorescein dye ratings for containment/leakage in 69 infants showed that 83% of single-use diapers and 30% of the cloth diapers were rated as having no or minor leakage of feces. Cultures were taken of laundered vinyl pants that had previously been used over cloth diapers to determine microbial contamination. Thirty-nine percent of the pants contained Gram-negative, lactose-fermenting bacilli indicating fecal contamination. This study comparing single-use and cloth diapers for containment of artificial feces by use of image analysis and fluorescein dye ratings showed better containment by single-use diapers. The study also raises the question of possible spread of feces-borne pathogens by the vinyl pants used over cloth diapers, particularly in a day-care center. PMID- 8441573 TI - Changes in carbohydrate composition in human milk over 4 months of lactation. AB - This study aimed to examine the carbohydrate content (monosaccharides, lactose, and oligosaccharides) of human milk over 4 months of lactation to determine whether any changes occurred over time. Milk samples from 46 mothers, who delivered at term, were collected at 4th, 10th, 30th, 60th, 90th, and 120th days after delivery. Carbohydrates were measured by high-pressure liquid chromatography. Mean lactose concentration (+/- SD) increased from 56 +/- 6.06 g/L on day 4 to 68.9 +/- 8.16 g/L on day 120. Oligosaccharide level decreased from 20.9 +/- 4.81 g/L to 12.9 +/- 3.30 g/L, respectively. Monosaccharides represented only 1.2% of total carbohydrates. The changes in carbohydrate composition found indicate that carbohydrate synthesis by the mammary gland is a dynamic process. The physiological and biological relevance of human milk oligosaccharides is also discussed. PMID- 8441574 TI - Are children born to young mothers at increased risk of maltreatment? AB - Previous case-control or cross-sectional studies have provided conflicting results about whether children of teenage mothers are at increased risk of maltreatment compared with children of older mothers. This study is the first to examine this question using a longitudinal, cohort design and the first to address important methodologic issues such as detection bias. Subjects were 219 consecutive index children born to inner-city women who were 18 years or younger and 219 sociodemographically similar comparison children born to women 19 years or older. Data were collected by reviewing the medical records of each child through the fifth birthday. Three outcomes were examined: maltreatment, poor growth, and a change in the child's primary caretaker. Maltreatment was ascertained by having two experts, one of whom was blind to the group status, review each injury documented in the records. Predefined criteria were used to distinguish unintentional injuries from maltreatment (abuse, neglect, or sexual abuse). Maltreatment occurred more frequently in the children of young mothers (12.8%) than in the comparison group (6.4%) (risk ratio [RR] = 2.00; 95% confidence interval [CI] = 1.17, 3.64). Poor growth, defined by growth criteria, occurred in 6.9% of the index group and in 4.1% of comparison children (RR = 1.67; 95% CI = 0.75, 3.73). A change in the child's primary caretaker, either because of placement in foster care or because the mother left the home, occurred in 12.8% of the index group and in 3.2% in comparison children (RR = 4.00; 95% CI = 1.80, 8.87).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441575 TI - Behavioral and emotional problems among preschool children in pediatric primary care: prevalence and pediatricians' recognition. Pediatric Practice Research Group. AB - This study examined how well private-practice pediatricians can identify emotional/behavioral problems among preschool children. Children aged 2 through 5 (N = 3876) were screened during a visit to 1 of 68 pediatricians who rendered an opinion about the presence of emotional/behavioral problems. Subsequently, children who scored above the 90th percentile for behavioral problems on the Child Behavior Checklist, along with children matched on age, sex, and race who had screened low, were invited for an intensive second-stage evaluation. There were 495 mothers and children who participated in that evaluation, which included a behavioral questionnaire, maternal interview, play observation, and developmental testing. Two PhD-level clinical child psychologists rendered independent opinions about the presence of an emotional/behavioral disorder. The psychologists identified significantly higher rates of problems overall--13.0% when the criterion was independent agreement that the child had an emotional/behavioral problem and a regular psychiatric diagnosis was assigned, vs 8.7% based on pediatricians' ratings. Prevalence rates based on psychologists' independent ratings were significantly higher than pediatricians' for both sexes, 4- through 5-year-olds, and whites, but not for 2- through 3-year-olds, African Americans, and all minorities. Prevalence rates based on psychologists' ratings were significantly higher than the pediatricians' for all subgroups when V-code diagnoses were included in the psychologists' ratings. Overall, pediatricians' sensitivity was 20.5%, and specificity was 92.7%. At least 51.7% of the children who had an emotional/behavioral problem based on the psychologist's independent agreement had not received counseling, medication, or a mental health referral from the pediatrician.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441576 TI - School-based crisis intervention services for adolescents: position paper of the Committees on Adolescence and School Health, Connecticut Chapter of the American Academy of Pediatrics. PMID- 8441577 TI - Garlic burns. PMID- 8441578 TI - Developmentally disabled children recycle car seats: a win-win program. PMID- 8441579 TI - Maternal and neonatal hyperparathyroidism as a consequence of maternal renal tubular acidosis. PMID- 8441580 TI - Partial methylcrotonyl-coenzyme A carboxylase deficiency in an infant with failure to thrive, gastrointestinal dysfunction, and hypertonia. PMID- 8441581 TI - Recurrent hemolytic uremic syndrome secondary to Escherichia coli O157:H7 infection. PMID- 8441582 TI - Group health supervision visits more effective than individual visits in delivering health care information. PMID- 8441583 TI - American Academy of Pediatrics Committee on Hospital Care: child life programs. PMID- 8441584 TI - Evaluation of febrile infant. PMID- 8441585 TI - Familial vesicoureteral reflux. PMID- 8441586 TI - Saving young arms and batters' heads. PMID- 8441587 TI - Saddened not amused. PMID- 8441588 TI - Saddened not amused. PMID- 8441589 TI - Amused not saddened. PMID- 8441590 TI - Button battery recommendations questioned. PMID- 8441591 TI - Pelvic examination--an essential skill. PMID- 8441592 TI - [A study of the utility of the MR image for the diagnosis of thymic tumors- imaging and pathologic correlation]. AB - MR imaging was performed in 25 patients with thymic tumors (five with non invasive thymomas, 15 with invasive thymomas, and five with thymic carcinomas), and the MR imaging appearance was compared with the pathological findings. Non invasive thymomas showed generally oval or round masses with well-defined margins and homogeneous intensity on T1- and T2-weighted images. Invasive thymomas showed a multinodular appearance in 79% (11/15) of cases, and an internodular difference in signal intensity (IDSI) in 64% (7/11) on T2-weighted images. It was considered that the IDSI on T2-weighted images correlated pathologically with the hemorrhagic and/or necrotic areas and hyalinization. The IDSI seemed to be a characteristic finding of invasive thymomas. The histological findings and MR imaging appearance of thymomas were compared. The predominantly epithelial type showed a low incidence of nodular appearance but showed marked IDSI on T2 weighted images. Therefore, it is more likely that the predominantly epithelial type induced more varied intratumoral changes than other types. Extension of thymic carcinomas was similar to that of invasive thymomas on MR imaging, but thymic carcinomas showed no definite nodular appearance. In conclusion, MR images in thymic tumors were useful for not only determining the morphology of the tumor but also the tissue characteristics. Therefore, MR imaging can be a useful modality to correlate with the histological findings and biological behavior of thymic tumors. PMID- 8441593 TI - [CT angiography of the liver]. AB - The diagnostic efficacy of CT arterial portography (CTAP) for the hepatic tumors has been established. We developed the double-phase incremental CTAP (DP-CTAP) using a fast CT scanner, by which the double-phase scanning of the whole liver was made during a single contrast administration. The DP-CTAP was performed in 9 cases of hepatic diseases, and was useful for the lesion detection and improvement of the visualization of the liver vasculatures. The maximum density projection angiogram of the portal and hepatic veins was easily made by DP-CTAP images, and useful for three dimensional understanding of the liver vasculatures and the detection of the vascular abnormalities. PMID- 8441594 TI - [Kinetics of flomoxef sodium monitored with in vivo 19F NMR spectroscopy]. AB - The potential usefulness of in vivo 19F NMR spectroscopy for the monitoring of flomoxef sodium (FMOX) kinetics was evaluated. In the experimental study using phantom the minimum concentration of FMOX of which signals could be monitored with 19F NMR spectroscopy was 16 micrograms/ml. In patients with intravenous bolus injection and drip infusion of FMOX (2 g/100 ml), signals from normal heart, liver, and kidney were clearly monitored with 19F NMR spectroscopy. In normal lung any signal was not detected, but in a lung with a cancer associated massive atelectasis the monitoring of signals was possible with 19F NMR spectroscopy in both intravenous and intraarterial injections. Monitoring of FMOX kinetics with in vivo 19F NMR spectroscopy will be useful in clinical applications. PMID- 8441595 TI - [Evaluation of the invasion of esophageal cancer to the aorta by cine-MR imaging]. AB - We examined the usefulness of cine-MR imaging for evaluation of the invasion of esophageal cancer to the aorta in 12 cases. We used the technique of field echo pulse sequence. When the low intensity stripe was recognized between the tumor and the wall of aorta, we interpreted it as negative finding of the direct tumor invasion. By using this criteria, 11 of the 12 cases (92%) of the esophageal cancer for aortic wall invasion were correctly diagnosed as compared with 75% correct diagnosis by conventional MR imaging. PMID- 8441596 TI - [Diagnosis of myocardial infarction by cine MR imaging--a comparative study with thallium-201 myocardial SPECT]. AB - The usefulness of cine magnetic resonance (MR) imaging was evaluated in 41 patients with acute (4 cases), subacute (21 cases) and chronic (16 cases) myocardial infarctions on the basis of the findings of thallium-201 myocardial SPECT. The overall rate of diagnostic accordance between cine MR imaging and SPECT was 85.0% (408/480). It was highest at the middle of the left ventricle (89.0%, 146/164) and lowest at the base (82.7%, 129/156). Measurement of wall thickness using the images printed on films was possible in 87.1% of segments (418/480). There was a significant difference in end-diastolic wall thickness and %-thickening between the infarcted and non-infarcted sites except for the base of the left ventricle. However, diastolic wall thinning was not remarkable in acute cases of less than one week after onset. In these cases %-thickening may be useful. Partial volume averaging on MR imaging and the inaccuracy of SPECT findings at the base also made meaningful comparison difficult. The most important diagnostic findings of myocardial infarction on cine MR imaging were end-diastolic wall thinning and abnormal motion such as akinesis and dyskinesis. It is concluded that cine MR imaging is a useful noninvasive examination method for evaluating the status of cardiac function in myocardial infarction. PMID- 8441597 TI - [MR imaging of bone bruise associated with ACL tear]. AB - The authors reviewed 56 MR studies of the knee performed for suspected cruciate ligament tear at the Tokyo Metropolitan Hiroo Hospital from April 1990 to March 1991. There were 10 patients with abnormal signal in the subcortical bone marrow. Eight of these patients had concomitant anterior cruciate ligament (ACL) tear with no evidence of fracture on plain radiographs of the knee. The abnormal signals were all seen in the lateral compartment, almost invariably in the middle third of the lateral femoral condyle and posterolateral aspect of the tibial plateau, and were of low intensity on T1-weighted and proton density images and of high intensity on T2-weighted images. It was speculated that these abnormalities resulted from impaction of the lateral femoral condyle into the posterior lip of the tibial plateau due to rotary subluxation of the tibia. One patient had a follow-up study three months later, which revealed complete resolution of bone bruise. It was concluded that bone bruise associated with ACL tear is seen specific locations, which may be a useful secondary sign of acute ACL tear. PMID- 8441598 TI - [Detection of myocardial fatty components with ultrafast CT]. AB - Intramyocardial fatty components are sometimes depicted by CT of the thorax. However, no studies have investigated the distribution, frequency and cause of these components by using statistical analysis. Three hundred forty-five patients with various cardiac diseases were examined with an ultrafast CT scanner, and intramyocardial fatty components were detected in 15 (4.3%) of them. The frequency of intramyocardial fatty components in each disease was as follows: 6% in ischemic heart disease, 7% in Kawasaki disease, 11% in hypertrophic cardiomyopathy (HCM), 18% in dilated cardiomyopathy (DCM) and 33% in arrhythmogenic right ventricular dysplasia (ARVD). Except for patients with HCM, the segments of the ventricles, where the fatty components were detected, agreed well with the segments with asynergy in left ventriculography and/or the segments with perfusion defect in T1 myocardial scintigraphy. Thus, ischemic fatty degeneration was considered to be a main factor in the production of intramyocardial fatty components in these diseases. The focus of arrhythmia was sometimes detected in the segments with intramyocardial fatty components in DCM and ARVD cases. It is suspected that intramyocardial fatty components sometimes produce arrhythmia in these diseases. PMID- 8441599 TI - [Detection of myocardial damage in patients with dilated cardiomyopathy using ultrafast CT]. AB - The myocardial characteristics of DCM patients were investigated by ultrafast CT (UFCT), left ventriculography (LVG) and T1 myocardial scintigraphy (SCINTI). Late enhancement, focal wall thinning and intramyocardial fatty components were detected as focal abnormal findings by UFCT. The regions of asynergy detected by LVG and perfusion defect detected by SCINTI were well correlated with those of focal abnormal findings detected by UFCT. There were significant differences between patients with and without focal abnormal findings, in ejection fraction and end-diastolic pressure of left ventricle and the incidence of ventricular arrhythmia. It is possible that these focal abnormal findings represented focal ischemic myocardial damage in DCM patients. DCM patients were divided into two different functional groups by UFCT findings. PMID- 8441600 TI - [Estimation of risk due to radiation exposure in the mass screening of cancer in Japan]. AB - Five types of mass screening programs for cancer are performed under the auspices of the Adult Health Promoting Act of the Japanese Government. The cancers involved are those of stomach, uterus, lung, breast and colon. Radiological images are routinely used for the screening of stomach and lung cancers, and mammography will be employed in the near future. In this study, the risk due to radiation exposure in the above-mentioned screening programs was estimated for an individual who participates in the screening of each cancer annually. The dose absorbed at each screening was estimated and an additive risk model was used as the pattern of occurrence of radiation-induced cancers for simplicity. Safety was also estimated. Results showed that the risk of a shortened life-expectancy as a result of undergoing annual mass screening for breast, stomach and lung cancer was insignificant in comparison with the average life-expectancy of about 80 years for Japanese men and women, and much smaller than the benefit of mass screening expressed in terms of prolonged life-expectancy. However, it should be emphasized that a quality control program must be established to keep the dose absorbed at each X-ray screening examination as low as reasonably possible. PMID- 8441601 TI - [Radiation injury of the lung following postoperative radiotherapy of breast cancer using a single large portal technique--CT study]. AB - When postoperative radiotherapy for breast cancer is indicated, we employ a single large portal technique with electron beams using a bolus made of MIX-R (soft tissue equivalent material) for the chest wall. The entire lymph node groups as well as the chest wall are irradiated uniformly, and the total dose is 50 Gy, 2 Gy/fraction, 5 days/week. Radiation changes of the lung in 35 breast cancer patients irradiated by this technique were evaluated by computed tomographic (CT) studies. Radiation injuries were detected in 12 patients out of 35 (34%). Among patients who were irradiated by three portal techniques without bolus, radiation injuries were detected in all 4 patients (100%) by CT and in 39 patients out 72 (54%: historical control group) by plain chest film. These results indicated the superiority of the single large portal technique. Radiation injuries were identified in CT studies at 135 day after commencement of radiotherapy, and their distributions were localized to areas of 80-100% dose level. Measurements in CT revealed that the thickness of the chest wall varied extremely according to surgical procedures, so that the adequacy of the selection of energy of electron beams in each patient by CT was indispensable. PMID- 8441602 TI - [MR imaging of postoperative change of dura mater of rabbits--effect of contrast enhancement of dura mater & correlation with pathological findings]. AB - To explain the mechanism of benign postoperative dural enhancement, the author made experimental model of rabbit's subdural hematoma and performed magnetic resonance (MR) imaging with gadolinium-diethylenetriaminepentaacetic acid (Gd DTPA). On plain T1-weighted images, infused blood or red blood cells could not be detected immediately after surgery. On follow up plain T1-weighted images, the infused blood could be identified in only a case with 1 cc blood infusion. Marked dural enhancement could be seen immediately after surgery and continued three to fourteen days after 1 cc or 0.1 cc blood or 0.1 cc red blood cells infusion. To the contrary, no definite dural enhancement could be seen in the cases with plasma or saline infusion. Subdural red blood cells were required for dural enhancement immediately after surgery. Pathological findings revealed three types of reaction to infused blood: newly formed capillarization with fresh hemorrhage from the capillaries; subdural hematoma and no reaction. After vanishment of dural enhancement, pathological findings of the specimens were identical to that of normal dura. Dural enhancement may be induced by increased permeability of the dura associated with subdural hematoma and/or the extravasation of the contrast from newly formed capillaries. PMID- 8441603 TI - [Relation between the local effect of thermoradiotherapy and the prognosis for recurrent lung cancers]. AB - From October 1986 through December 1991, 30 patients with locally recurrent lung cancer were treated by local hyperthermia combined with radiotherapy at the Kawasaki Medical School Hospital. Local heat was applied with 13.56 MHz radiofrequency (RF) capacitive heating equipment twice a week after radiotherapy for 40-60 minutes per session. The tumor temperatures of only a few patients (three patients) could be measured directly by thermocouples inserted into the tumors because of anatomical difficulties. Based on thermometrical results, it was estimated that the maximum tumor temperature was about 41 degrees C. When we consider the extensive low density areas often appearing in CT scan images following this combined therapy (NR2), the tumor response was as follows: CR 0, PR 5 (18%), NR 13 (40%), NR2 10 (36%), and PD 0. The local response rate (CR+PR+NR2) was 54%. The median survival time after the onset of retreatment was 12.8 months in PR cases, 7.1 months in NR cases and 24.1 months in NR2 cases. There was a statistically significant difference (p < 0.01) in the median survival times for NR and NR2 cases. From the standpoint of prognosis, we concluded that NR2 was a condition comparatively similar to clinical PR. PMID- 8441604 TI - [Experimental study of tumor response to twice-a-day irradiation at smaller doses than 2 Gy]. AB - Tumor response to twice-a-day irradiation (BID) at smaller doses than 2 Gy on mammary carcinoma of C3H/He mouse (alpha/beta ratio = 18 Gy) was studied with comparison of once-a-day irradiation (QD) in the same overall treatment time. The dose per fraction (dBID) was ranged from 110R to 162R in BID, and the dose per fraction (dQD) was ranged from 200R to 300R in QD fractionation (1R = 0.91 cGy). The number of fraction was 10 or 15 in QD, and 20 or 30 in BID. The interval of fractions was 4 hours in BID. Tumor response was assessed by tumor growth delay. MFD effect ratio, i.e., growth delay time of BID/growth delay time of QD, was significantly smaller than the ratio estimated from FDF formula, (alpha/beta + dBID) x dBID x NBID/(alpha/beta + dQD) x dQD x NQD, with decreasing fraction size. In the case of dBID = 120R and dQD = 200R, estimated ratio was 1.16, but MFD effect ratio was 0.58, regardless of 20% increments of daily dose. To get same or more tumor response, it is necessary to prolong the overall treatment time of twice-a-day irradiation. If the overall treatment time is same, it is estimated that the fraction size of BID equivalent to the fractionation of daily 200R is presumably 135R to this mouse tumor. PMID- 8441605 TI - Homology in accessory proteins of replicative polymerases--E. coli to humans. PMID- 8441606 TI - Contacts between mammalian RNA polymerase II and the template DNA in a ternary elongation complex. AB - Elongation complexes of RNA polymerase II, RNA-DNA-enzyme ternary complexes, are intermediates in the synthesis of all eukaryotic mRNAs and are potential regulatory targets for factors controlling RNA chain elongation and termination. Analysis of such complexes can provide information concerning the structure of the catalytic core of the RNA polymerase and its interactions with the DNA template and RNA transcript. Knowledge of the structure of such complexes is essential in understanding the catalytic and regulatory properties of RNA polymerase. We have prepared and isolated complexes of purified RNA polymerase II halted at defined positions along a DNA template, and we have used deoxyribonuclease I (DNAse I) to map the interactions of the polymerase with the DNA template. DNAse I footprints of three specific ternary complexes reveal that the enzyme-template interactions of individual elongation complexes are not identical. The size of the protected region is distinct for each complex and varies from 48 to 55 bp between different complexes. Additionally, the positioning of the protected region relative to the active site varies in different complexes. Our results suggest that RNA polymerase II is a dynamic molecule and undergoes continual conformational transitions during elongation. These transitions are likely to be important in the processes of transcript elongation and termination and their regulation. PMID- 8441607 TI - Cloning, chromosomal localization and expression pattern of the POU domain gene Oct-11. AB - POU domain genes encode a family of highly conserved transacting factors that influence the transcriptional activity of several cell type-specific and ubiquitous genes. We have cloned and sequenced cDNAs encoding a novel mouse POU domain protein, Oct-11, that is closely related within the POU domain to the POU class II proteins, Oct-1 and Oct-2. Recombinant Oct-11 protein binds specifically to an octamer sequence in vitro. The Oct-11 gene is expressed during mouse embryogenesis and in the adult thymus and testis. In addition, it is abundant in the myeloma cell line P3/NS-1/1-Ag4.1. We describe the structure of Oct-11 and its chromosomal localization, and discuss the evidence that the POU class II gene family has evolved by duplication and divergence of a common ancestral gene. PMID- 8441608 TI - Happy mapping: linkage mapping using a physical analogue of meiosis. AB - We have devised a simple method for ordering markers on a chromosome and determining the distances between them. It uses haploid equivalents of DNA and the polymerase chain reaction, hence 'happy mapping'. Our approach is analogous to classical linkage mapping; we replace its two essential elements, chromosome breakage and segregation, by in vitro analogues. DNA from any source is broken randomly by gamma-irradiation or shearing. Markers are then segregated by diluting the resulting fragments to give aliquots containing approximately 1 haploid genome equivalent. Linked markers tend to be found together in an aliquot. After detecting markers using the polymerase chain reaction, map order and distance can be deduced from the frequency with which markers 'co-segregate'. We have mapped 7 markers scattered over 1.24 Mbp using only 140 aliquots. Using the 'whole-genome' chain reaction, we also show how the approach might be used to map thousands of markers scattered throughout the genome. The method is powerful because the frequency of chromosome breakage can be optimized to suit the resolution required. PMID- 8441609 TI - Rotational symmetry in ribonucleotide strand requirements for binding of HIV-1 Tat protein to TAR RNA. AB - Transactivation of human immunodeficiency virus (HIV) gene expression requires binding of the viral Tat protein to a RNA hairpin-loop structure (TAR) which contains a two or three-nucleotide bulge. Tat binds in the vicinity of the bulge and the two adjacent duplex stems, recognising both specific sequence and structural features of TAR. Binding is mediated by an arginine-rich domain, placing Tat in the family of arginine-rich RNA binding proteins that includes other transactivators, virus capsid proteins and ribosome binding proteins. In order to determine what features of TAR allow Tat to bind efficiently to RNA but not DNA forms, we examined Tat binding to a series of RNA-DNA hybrids. We found that only one specific strand in each duplex stem region needs to be RNA, implying that interaction between Tat and a given stem may be solely or predominantly with one of the two strands. However, the essential strand is not the same one for each stem, suggesting a switch in the bound strand on opposing sides of the bulge. PMID- 8441610 TI - An RNasin-resistant ribonuclease selective for interleukin 2 mRNA. AB - Interleukin 2 (IL2) mRNA has a short half-life in the cytoplasm of T lymphocytes, relative to most mRNA. We have discovered a candidate ribonuclease to account for the rapid turnover of IL2 mRNA in the cytosol of the human T lymphocyte cell line Jurkat. In partially purified form, this RNase is about 7 times as active on IL2 as on beta-globin mRNA. Pancreatic RNase, by contrast, does not show a significant preference for IL2 mRNA. Neither 5' capping, nor polyadenylation of the substrate mRNAs affects their degradation by the IL2-selective mRNase, whose activity is optimal in 0.5 mM Mg++ and 100 mM potassium acetate. The mRNase behaves like a protein of molecular weight 60-70,000 on gel chromatography, and is unusual in that it is insensitive to placental RNase inhibitor (RNasin). The mRNase cleaves IL2 mRNA at a small number of sites in the coding region, and IL2 mRNA containing only the coding region and 36 nucleotides of the 3'-noncoding region competes efficiently with full-length IL2 mRNA for the mRNase, whereas beta-globin mRNA does not. PMID- 8441611 TI - A complete nucleolin cDNA sequence from Xenopus laevis. PMID- 8441612 TI - Cloning and sequence of the rat retinoblastoma (Rb) gene cDNA. PMID- 8441613 TI - PCR amplification of DNA sequences from nitrocellulose-bound, immunostained bacterial colonies. PMID- 8441614 TI - Large-scale production of DNA sequencing templates by microtitre format PCR. PMID- 8441615 TI - Interspersed repetitive sequence (IRS)-PCR amplification of pulsed-field gel fractionated DNA to derive markers from the incontinentia pigmenti 1 (IP1) locus. PMID- 8441616 TI - Modification interference approach to detect ribose moieties important for the optimal activity of a ribozyme. AB - A new approach for modification interference studies is presented. It involves the use of phosphorothioates as a handle to analyze any desired base or sugar modification. This method was applied to identify ribose and phosphate moieties which could be important in the pre-tRNA recognition of E. coli RNase P RNA (M1 RNA). The utility of this technique was confirmed by detecting the inhibitory effect of a deoxyribose in the 5'-flank (position-1). This site was already known to interfere with RNase P cleavage, if modified. We have analyzed pre-tRNA(Tyr) and pre-tRNA(Phe) and found different interference patterns for both tRNAs. Two unpaired regions were involved in both pre-tRNAs. Phosphorothioates interfered at the transition between acceptor- and D-arms. The results with deoxythymidines in the T-loop indicated that deoxyribose moieties or the extra methyl group in thymidine could interfere with RNAse P cleavage. These data suggest that even in complete pre-tRNAs, only a few intact ribonucleotides are important in the substrate recognition by RNase P. We have demonstrated the potential of this new approach which offers many future applications in all fields involving nucleic acids, for example RNA processing, action of ribozymes, tRNA charging and studies related to DNA promoter recognition. PMID- 8441617 TI - Telomere directed fragmentation of mammalian chromosomes. AB - Cloned human telomeric DNA can integrate into mammalian chromosomes and seed the formation of new telomeres. This process occurs efficiently in three established human cell lines and in a mouse embryonic stem cell line. The newly seeded telomeres appear to be healed by telomerase. The seeding of new telomeres by cloned telomeric DNA is either undetectable or very inefficient in non tumourigenic mouse or human somatic cell lines. The cytogenetic consequences of the seeding of new telomeres include large chromosome truncations but most of the telomere seeding events occur close to the pre-existing ends of natural chromosomes. PMID- 8441618 TI - Change of the higher order structure of DNA induced by the complexation with intercalating synthetic polymer, as is visualized by fluorescence microscopy. AB - The electrophoretic movement and Brownian motion of T4DNA, lambda DNA and their complexes with polyacrylamide (PAAm) via intercalative unit from 5-[(4 acryloylamino)phenyl]-3-amino-7-(dimethylamino)-2-methylp henazinium chloride were observed using fluorescence microscopy. It was found that T4DNA/PAAm complex migrates slower than T4DNA alone in gel electrophoresis, although they exhibit similar conformational change during the migration. Quantitative analyses of the translational diffusion of the lambda DNA and its complex in solution demonstrate that the DNA molecules extend due to intercalative binding of PAAm, suggesting the pseudo-grafting structure of the complex. PMID- 8441619 TI - Influence of tRNA tertiary structure and stability on aminoacylation by yeast aspartyl-tRNA synthetase. AB - Mutations have been designed that disrupt the tertiary structure of yeast tRNA(Asp). The effects of these mutations on both tRNA structure and specific aspartylation by yeast aspartyl-tRNA synthetase were assayed. Mutations that disrupt tertiary interactions involving the D-stem or D-loop result in destabilization of the base-pairing in the D-stem, as monitored by nuclease digestion and chemical modification studies. These mutations also decrease the specificity constant (kcat/Km) for aspartylation by aspartyl-tRNA synthetase up to 10(3)-10(4) fold. The size of the T-loop also influences tRNA(Asp) structure and function; change of its T-loop to a tetraloop (-UUCG-) sequence results in a denatured D-stem and an almost 10(4) fold decrease of kcat/Km for aspartylation. The negative effects of these mutations on aspartylation activity are significantly alleviated by additional mutations that stabilize the D-stem. These results indicate that a critical role of tertiary structure in tRNA(Asp) for aspartylation is the maintenance of a base-paired D-stem. PMID- 8441620 TI - Different TBP-associated factors are required for mediating the stimulation of transcription in vitro by the acidic transactivator GAL-VP16 and the two nonacidic activation functions of the estrogen receptor. AB - The estrogen receptor (ER) contains two nonacidic transcriptional activation functions, AF-1 and AF-2 (formerly TAF-1 and TAF-2). In this study we show that AF-1 and AF-2 are able to stimulate transcription in vitro in a HeLa cell system when fused to the DNA binding domain of the yeast activator GAL4. We also demonstrate that a factor(s) required for the function of the ER AFs is chromatographically separable from a factor(s) necessary for the activity of the acidic activation domain of VP16. Moreover, immunoprecipitation experiments using a monoclonal antibody directed against the TATA box binding protein (TBP) indicate, that these different factors are associated with TBP in distinct TFIID complexes. PMID- 8441621 TI - Glucose repression of lactose/galactose metabolism in Kluyveromyces lactis is determined by the concentration of the transcriptional activator LAC9 (K1GAL4) [corrected]. AB - In the budding yeast Kluyveromyces lactis glucose repression of genes involved in lactose and galactose metabolism is primarily mediated by LAC9 (or K1GAL4) the homologue of the well-known Saccharomyces cerevisiae transcriptional activator GAL4. Phenotypic difference in glucose repression existing between natural strains are due to differences in the LAC9 gene (Breunig, 1989, Mol.Gen.Genet. 261, 422-427). Comparison between the LAC9 alleles of repressible and non repressible strains revealed that the phenotype is a result of differences in LAC9 gene expression. A two-basepair alteration in the LAC9 promoter region produces a promoter-down effect resulting in slightly reduced LAC9 protein levels under all growth conditions tested. In glucose/galactose medium any change in LAC9 expression drastically affects expression of LAC9 controlled genes e.g. those encoding beta-galactosidase or galactokinase revealing a strong dependence of the kinetics of induction on the LAC9 concentration. We propose that in tightly repressible strains the activator concentration drops below a critical threshold that is required for induction to occur. A model is presented to explain how small differences in activator levels are amplified to produce big changes in expression levels of metabolic genes. PMID- 8441622 TI - Dispensable role of the NF-kappa B sites in the UV-induction of the HIV-1 LTR in transgenic mice. AB - We have previously reported the epidermis-specific expression of the HIV-1 LTR in transgenic mice and its induction by UV-B rays. To dissect the underlying mechanism of the UV induction of the LTR in mice, we developed two approaches. We first demonstrated by gel mobility shift analysis, using mice epidermal extracts, that the NF-kappa B sites of the HIV-1 LTR were one of the targets of the UV induction. The Sp-1 sites and the potential AP-1 sites of the LTR were not involved in this phenomenon. The transient transfection assays of modified LTR in HeLa cells also demonstrated the involvement of the NF-kappa B sites in the UV induction and were consistent with previously published data. Secondly, to study the regulation acting on an integrated gene, we generated transgenic mice carrying the lacZ gene under the control of the partially deleted LTR. All the transgenic lines and unexpectedly those carrying the LTR deleted for the kappa B sites displayed a UV-inducible epidermal expression. This suggests that, in mice, the UV induction might be mediated through other sites than the kappa B sites and may also depend on changes of the chromatin state. PMID- 8441623 TI - Nucleotide sequence of 5' portion of srfA that contains the region required for competence establishment in Bacillus subtilus. AB - The nucleotide sequence of the 20,535 base pairs of the 5' end of the srfA operon, containing the region required for competence development, was determined. This included the srfA promoter region, the first open reading frame, srfAA, encoding surfactin synthetase I and part of the second open reading frame, srfAB, encoding surfactin synthetase II. Three amino acid-activating domains characteristic of those found in peptide synthetases could be discerned in both srfAA (activating Glu, Leu and D-Leu) and srfAB (activating Val, Asp, and D-Leu). The presence of a conserved spacer motif in the amino-terminal end of srfAA suggests that the srfAA product may not initiate surfactin synthesis. The portion of srfA that contains the region required for competence is composed of srfAA and the first amino acid-activating domain of srfAB. PMID- 8441624 TI - Atomic force microscopy of oriented linear DNA molecules labeled with 5nm gold spheres. AB - The atomic force microscope (AFM;1) can image DNA and RNA in air and under solutions at resolution comparable to that obtained by electron microscopy (EM) (2-7). We have developed a method for depositing and imaging linear DNA molecules to which 5nm gold spheres have been attached. The gold spheres facilitate orientation of the DNA molecules on the mica surface to which they are absorbed and are potentially useful as internal height standards and as high resolution gene or sequence specific tags. We show that by modulating their adhesion to the mica surface, the gold spheres can be moved with some degree of control with the scanning tip. PMID- 8441625 TI - Regional base composition variation along yeast chromosome III: evolution of chromosome primary structure. AB - The recent determination of the complete sequence of chromosome III from the yeast Saccharomyces cerevisiae allows, for the first time, the investigation of the long range primary structure of a eukaryotic chromosome. We have found that, against a background G+C level of about 35%, there are two regions (one in each chromosome arm) in which G+C values rise to over 50%. This effect is seen in silent sites within genes, but not in noncoding intergenic sequences. The variation in G+C content is not related to differential selection of synonymous codons, and probably reflects mutational biases. That the intergenic regions do not exhibit the same phenomenon is particularly interesting, and suggests that they are under substantial constraint. The yeast chromosome may be a model of the structure of the human genome, since there is evidence that it is also a mosaic of long regions of different base compositions, reflected in wide variation of G+C content at silent sites among genes. Two possible causes of this regional effect, replication timing, and recombination frequency, are discussed. PMID- 8441626 TI - Cross-ligation and exchange reactions catalyzed by hairpin ribozymes. AB - The negative strand of the satellite RNA of tobacco ringspot virus (sTobRV(-)) contains a hairpin catalytic domain that shows self-cleavage and self-ligation activities in the presence of magnesium ions. We describe here that the minimal catalytic domain can catalyze a cross-ligation reaction between two kinds of substrates in trans. The cross-ligated product increased when the reaction temperature was decreased during the reaction from 37 degrees C to 4 degrees C. A two-stranded hairpin ribozyme, divided into two fragments between G45 and U46 in a hairpin loop, showed higher ligation activity than the nondivided ribozyme. The two stranded ribozyme also catalyzed an exchange reaction of the 3'-portion of the cleavage site. PMID- 8441627 TI - The ble resistance gene as a new selectable marker for Trypanosoma brucei: fly transmission of stable procyclic transformants to produce antibiotic resistant bloodstream forms. AB - We describe here the stable transformation of Trypanosoma brucei using a new selectable marker for kinetoplastid protozoa, the Sh ble, or phleomycin, resistance gene. A plasmid containing this gene targeted to the tubulin gene locus by homologous sequences was introduced into procyclic trypanosomes by electroporation and cells selected for antibiotic resistance. Southern analysis of stable transformants showed that the plasmid had been integrated into the tubulin locus by homologous recombination. Analysis of bloodstream stage transformants, produced by transmission through the vector Glossina, showed that the resistance gene was conserved and expressed in these forms in the absence of selective drug pressure. In both procyclic and bloodstream forms, transcription of the ble gene appears to originate from the upstream tubulin promoter, despite the presence of a VSG promoter in the integrated construct. The generation of stable bloodstream transformants for the first time will facilitate the study of gene function and expression during the trypanosome life cycle, and aid in the investigation of genetic exchange in these organisms. PMID- 8441628 TI - Folding of DNA substrate-hairpin ribozyme domains: use of deoxy 4-thiouridine as an intrinsic photolabel. AB - Hairpin ribozymes derived from (-)sTRSV RNA exhibit substantial cleavage activity when wobble GU base pairs are introduced in place of the AU pairs normally involved in helices I and II between substrate and ribozyme. This finding prompted us to synthesize by in vitro transcription a new hairpin ribozyme, active against a 14-mer substrate derived from a conserved HIV sequence. Interactions of the canonical and anti-HIV hairpin ribozymes with non cleavable DNA substrate analogues containing the photoaffinity probe deoxy-4-thiouridine (ds4U) at a single site were investigated. Upon near-UV light irradiation (365 nm), all these substrate analogues were covalently attached to ribozyme via single or multiple crosslinks. In contrast, no crosslinks were detected using either a DNA substrate analogue lacking ds4U or a ds4U containing oligomer unrelated to the substrate sequence. As expected, if the dissociation constant is in the range of 5-15 microM, the yield of crosslinked ribozyme increased markedly with increasing the substrate analogue concentration. The ribozyme residues involved in the crosslinks were determined by RNA sequencing. The pattern of crosslinks obtained with the two ribozyme systems provides additional evidence in support of the consensus secondary structure proposed for the hairpin domain. Minor alternative conformations were detected in the case of the (-)sTRSV system. PMID- 8441629 TI - A factor stimulating transcription of the testis-specific Pgk-2 gene recognizes a sequence similar to the binding site for a transcription inhibitor of the somatic type Pgk-1 gene. AB - The glycolytic enzyme phosphoglycerate kinase (PGK) consists of two isozymes, somatic-type PGK-1 and testis-specific PGK-2. The isozyme switch from PGK-1 to PGK-2 occurs during spermatogenesis at the mRNA level. The distal upstream region of the gene encoding mouse PGK-2 (Pgk-2) possesses a silencer-like negative cis element. In the present study, a positive cis element located in the proximal upstream region and factor(s) bound to it were analyzed in vitro. Cell-free transcription using nuclear extracts of rat organs demonstrated that the region between nucleotide positions -82 and -64, relative to the most distal transcription initiation site at +1, stimulates transcription in testis extracts. The cis element did not act on the promoter of the thymidine kinase gene, suggesting that it stimulates Pgk-2 transcription in a promoter-specific manner. The cis element bound a nuclear factor(s), which we designated TAP-1. Introducing various base substitutions within the cis element revealed that TAP-1-binding to the element requires the sequence 5'-GGAA-3', which is the binding motif for Ets oncoproteins. We previously reported that TIN-1, a transcription inhibitor of Pgk 1, binds to a sequence similar to the Ets-binding site. The addition of an oligo DNA containing the TIN-1-binding sequence of Pgk-1 prevented TAP-1 from binding to the Pgk-2 cis element, and vice versa. These results suggest that both TIN-1 and TAP-1, which are presumably involved in transcription regulation of the two Pgk genes, recognize DNA sequences related to the Ets-binding motif. PMID- 8441630 TI - Structural and functional properties of ribosomal protein L7 from humans and rodents. AB - By subtractive screening of a library made from mRNA of lipopolysaccharide (LPS) stimulated mouse B lymphocytes we isolated cDNA-clones encoding the ribosomal protein L7. Human L7 mRNA was cloned from activated T-lymphocytes. Although no specific function of L7 in the translation apparatus is known as yet, it should be a critical one as indicated by its high degree of structural conservation during evolution and its regulated expression in lymphoid cells. Human and rodent L7 proteins carry sequences similar to the basic-region-leucine-zipper(BZIP) motif of DNA-binding eucaryotic transcription factors. We show here that the region of L7 carrying the latter motif mediates L7-dimerization and stable binding to DNA and RNA. A preferential binding to RNA-structures is demonstrated. PMID- 8441631 TI - Differential expression of human nicotinic acetylcholine receptor alpha subunit variants in muscle and non-muscle tissues. AB - The nicotinic acetylcholine receptor (nAChR) is an oligomeric transmembrane glycoprotein consisting of four homologous subunits in stoichiometry of alpha 2, beta (gamma or epsilon). Recently the presence of a novel exon (P3A) in human alpha AChR gene has been reported. Two variants of the human alpha subunit arise from alternate RNA splicing, one with and one without the P3A exon. However, the evolutionary origin of the P3A exon and the regulation of the expression of the two variants in human muscle and non-human tissues is currently unknown. Examination of genomic DNA from various species shows that the P3A exon sequence is present only in hominoids, old world and new world primates species and is absent in the muscle cDNA or genomic DNA from rat, mouse or dog, indicating that P3A exon is evolutionary conserved for at least 50 million years. The P3A+ variant of alpha subunit was found to be constitutively expressed in skeletal muscle, brain, heart, kidney, liver, lung and thymus, while P3A-variant was differentially expressed only in skeletal muscle. Thus it appears that the P3A+ variant is generated by 'default' selection by the splicing machinery, while expression of the P3A- variant is regulated by tissue-specific factors in the skeletal muscle. Mechanisms regulating differential expression of the alpha subunit variants may be pertinent to the pathophysiology of myasthenia gravis. PMID- 8441632 TI - Mouse Oct-1 contains a composite homeodomain of human Oct-1 and Oct-2. AB - Members of the Oct family of transcription factors specifically interact with the octamer motif, ATGC-AAAT, a regulatory element important for tissue- and cell specific transcription as well as for the expression of housekeeping genes. Except for Oct-1, all Oct factors are expressed in a temporally and spatially restricted mode during murine development and their number varies in a given cell type. Despite its ubiquitous expression pattern Oct-1 may play a role in murine development. As a first step towards elucidating the role of Oct-1 we report the complementary DNA cloning of the mouse Oct-1 gene. Two large transcripts of 5 and 14 kb are derived from a single gene. The expression patterns of three splicing products of Oct-1 are similar in a number of cells and tissues. In the POU region murine Oct-1 differs in four amino acids from the human homologue and these differences are restricted to helices 1 and 2. Interestingly, two of the four variant amino acids are identical to those in human and mouse Oct-2 and thus the murine Oct-1 homeodomain is intermediary in sequence between human Oct-1 and Oct 2. These two amino acids together with a third one have been shown to be relevant for the interaction between human Oct-1 and herpes simplex virus transactivator VP16. Nevertheless, VP16 interacts albeit weakly with murine Oct-1. We speculate that the differences in the human and mouse Oct-1 homeodomains reflect host specific differences in protein-protein interactions. PMID- 8441633 TI - cDNA cloning of human N-Oct3, a nervous-system specific POU domain transcription factor binding to the octamer DNA motif. AB - Octamer transcription factors (Oct or OTF) are a subset of the POU family of transcription factors which regulate transcription of cellular and viral genes by binding to the octamer sequence motif ATGCAAAT. Neurons and astroglial cells harbour, in addition to the ubiquitous Oct 1 factor, at least four specific factors termed N-Oct 2,3,4 and 5. Here we report the cloning of a human brain derived cDNA that encodes the N-Oct 3 protein (443 aa) which is the human counterpart of the murine brain-2 gene product. Extracts from mammalian cells transfected with an N-Oct 3 expression vector yield three octamer DNA binding complexes in the electrophoretic mobility shift assay (EMSA): N-Oct 3 and two smaller complexes comigrating with the N-Oct 5A and 5B proteins of brain extracts. We present data suggesting that the N-Oct 5A and 5B proteins are generated by alternative translation initiation at internal AUG residues which are located before the POU domain. In contrast to the putative N-Oct 5 proteins, which are transcriptionally inert, the N-Oct 3 protein activates transcription from a reporter gene promoter with an octamer sequence, when transiently expressed in HeLa cells. PMID- 8441634 TI - Organization and nucleotide sequence of the DNA polymerase gene from the archaeon Pyrococcus furiosus. AB - We cloned the gene encoding the thermostable DNA polymerase from the archaeon Pyrococcus furiosus. The DNA fragment of 2785 base pair (bp) containing the structural gene for DNA polymerase was sequenced. DNA polymerase (Pfu polymerase), as deduced from the DNA sequence, consisted of 775 amino acids, had a molecular weight of 90, 109, and was structurally homologous to the alpha-like DNA polymerases (family B) represented by human DNA polymerase alpha and Escherichia coli DNA polymerase II. An unrooted phylogenetic tree of the alpha like DNA polymerases based on the amino acid sequence alignment was constructed. Pfu polymerase, with two other archaeon polymerases, constitutes a group with some animal viruses. The transcription initiation sites of the pol gene were identified by analysis of in vivo transcripts of both from P. furiosus and E. coli, and the promoters were assigned upstream of the pol coding region. A typical promoter sequence for the archaeon was found at a reasonable distance from the transcription initiation site in P. furiosus. PMID- 8441635 TI - Domain structure of a human general transcription initiation factor, TFIIF. AB - The structural and functional domains of a general transcription initiation factor, TFIIF (RAP30/74, FC), have been investigated using various deletion mutants of each subunit, both in vivo and in vitro. An in vivo assay showed that the N-terminal sequence containing residues of 1-110 of RAP30 that is located close to a sigma homology region interacts with a minimum sequence of residues 62 171 of RAP74 to form a heteromeric interaction. Reconstitution of in vitro transcription activity by deletion mutants of RAP74 clearly indicated that both N terminal residues 73-205 and C-terminal residues 356-517 are essential for full activity, the former interacting with RAP30, thus complexing with RNA polymerase II. From these data, the functional significance of domain structure of TFIIF is discussed in terms of its sigma homology sequences and complex formation with RNA polymerase II in the initiation and elongation of transcription. PMID- 8441636 TI - Structural requirements for the functional activity of a U1 snRNA gene enhancer. AB - The transcriptional enhancer of a chicken U1 small nuclear RNA (snRNA) gene contains a GC-box, an octamer motif, and an SPH motif that are recognized by the transcription factors Sp1, Oct-1, and SBF respectively. Previous work indicated that the octamer and the SPH motifs were both required for U1 gene enhancer activity in frog oocytes when the U1 gene was coinjected with a competing snRNA gene template. Here we show that neither two copies of the octamer motif, nor two copies of the SPH motif, can effectively substitute for the natural combination of octamer and SPH. Furthermore, neither the octamer nor the SPH motif (in the absence of the other) functioned efficiently in combination with a GC-box. Alteration of the spacing between the octamer and SPH motifs also reduced U1 template activity. Several potential cis-acting elements other than the SPH motif, with one possible exception among those tested, were unable to cooperate with the octamer motif to effectively enhance U1 gene expression. These results indicate that rather stringent structural requirements exist with respect to the essential cis-acting motifs present in the U1 enhancer, possibly reflecting the unique properties of the transcription complexes assembled on snRNA gene promoters. PMID- 8441637 TI - The cysteine conserved among DNA cytosine methylases is required for methyl transfer, but not for specific DNA binding. AB - All DNA (cytosine-5)-methyltransferases contain a single conserved cysteine. It has been proposed that this cysteine initiates catalysis by attacking the C6 of cytosine and thereby activating the normally inert C5 position. We show here that substitutions of this cysteine in the E. coli methylase M. EcoRII with either serine or tryptophan results in a complete loss of ability to transfer methyl groups to DNA. Interestingly, mutants with either serine or glycine substitution bind tightly to substrate DNA. These mutants resemble the wild-type enzyme in that their binding to substrate is not eliminated by the presence of non-specific DNA in the reaction, it is sensitive to methylation status of the substrate and is stimulated by an analog of the methyl donor. Hence the conserved cysteine is not essential for the specific stable binding of the enzyme to its substrate. However, substitution of the cysteine with the bulkier tryptophan does reduce DNA binding. We also report here a novel procedure for the synthesis of DNA containing 5-fluorocytosine. Further, we show that a DNA substrate for M. EcoRII in which the target cytosine is replaced by 5-fluorocytosine is a mechanism-based inhibitor of the enzyme and that it forms an irreversible complex with the enzyme. As expected, this modified substrate does not form irreversible complexes with the mutants. PMID- 8441638 TI - Sequence-specific and mechanism-based crosslinking of Dcm DNA cytosine-C5 methyltransferase of E. coli K-12 to synthetic oligonucleotides containing 5 fluoro-2'-deoxycytidine. AB - The product of the dcm gene is the only DNA cytosine-C5 methyltransferase of Escherichia coli K-12; it catalyses transfer of a methyl group from S-adenosyl methionine (SAM) to the C-5 position of the inner cytosine residue of the cognate sequence CCA/TGG. Sequence-specific, covalent crosslinking of the enzyme to synthetic oligonucleotides containing 5-fluoro-2'-deoxycytidine is demonstrated. This reaction is abolished if serine replaces the cysteine at residue #177 of the enzyme. These results lend strong support to a catalytic mechanism in which an enzyme sulfhydryl group undergoes Michael addition to the C5-C6 double bond, thus activating position C-5 of the substrate DNA cytosine residue for electrophilic attack by the methyl donor SAM. The enzyme is capable of self-methylation in a DNA-independent reaction requiring SAM and the presence of cysteine at position #177. PMID- 8441639 TI - An anti-parallel triple helix motif with oligodeoxynucleotides containing 2' deoxyguanosine and 7-deaza-2'-deoxyxanthosine. AB - Triple helix formation of oligodeoxynucleotides (ODNs) with a 15 base pair poly purine DNA target in the HER2 promoter was examined by footprinting analysis. 7 deaza-2'-deoxyxanthosine (dzaX) was identified as a purine analogue of thymidine (T) which forms dzaX:A-T triplets. ODNs containing 2'-deoxyguanosine (G) and dzaX were found to form triple helices in an anti-parallel orientation, with respect to the poly-purine strand of the target DNA. In comparative studies under physiological K+ and Mg++ concentrations and at pH 7.2, the ODNs containing G and dzaX showed high affinity to the target sequence while the ODNs containing G and T were not able to bind. In the absence of added monovalent salts both ODNs showed high affinity to the target sequence. The substitution of 7-deaza-2' deoxyguanosine for G substantially decreased the capacity of the ODNs to form triple helices under physiological conditions, indicating that dzaX may be unique in its ability to enhance triple helix formation in the anti-parallel motif. PMID- 8441640 TI - The helix-loop-helix containing transcription factor USF binds to and transactivates the promoter of the p53 tumor suppressor gene. AB - Expression of the wild-type p53 tumor suppressor gene has been found to play an important role in the regulation of cellular proliferation and differentiation. In addition, in many transformed cells and primary tumors, the gene has undergone allelic deletions and mutant forms of the p53 gene are expressed at elevated levels. In defining transcriptional regulatory regions of the p53 gene, we have previously shown that both the human and murine p53 promoters contain a conserved consensus recognition sequence for the basic-helix-loop-helix (bHLH) containing family of DNA-binding proteins. In the murine p53 promoter this element is required for full promoter activity and contains the sequence CACGTG, a sequence identical to the recognition site for the bHLH containing transcription factors c Myc, USF and TFE3. Here we examine the ability of one of these factors, USF, to bind to the p53 promoter. By assaying the binding activity of in vitro translated USF as well as factors present in nuclear extracts, we conclude that the transcription factor USF binds in a site-specific manner to a CACGTG motif within the murine p53 promoter and represents the major DNA-binding activity observed in nuclear extracts. Elevated levels of USF, generated upon transfection of a vector expressing USF, lead to enhanced activity of the p53 promoter. These findings indicate that USF may play a central role in regulating p53 expression. PMID- 8441641 TI - Cloning and analysis of the S2 ribosomal protein cDNA from Drosophila. PMID- 8441642 TI - The virB operon of the Agrobacterium tumefaciens virulence regulon has sequence similarities to B, C and D open reading frames downstream of the pertussis toxin operon and to the DNA transfer-operons of broad-host-range conjugative plasmids. PMID- 8441643 TI - Sequence of the 5.8S ribosomal gene of pathogenic and non-pathogenic isolates of Entamoeba histolytica. PMID- 8441644 TI - The gene for serine tRNA having anticodon sequence CAG in a pathogenic yeast, Candida albicans. PMID- 8441645 TI - I-Sce III: a novel group I intron-encoded endonuclease from the yeast mitochondria. PMID- 8441646 TI - Modified glutathione S-transferase fusion proteins for simplified analysis of protein-protein interactions. PMID- 8441647 TI - A simplified and reliable protocol for plasmid DNA sequencing: fast miniprep and denaturation. PMID- 8441648 TI - DNA sequences at immunoglobulin switch region recombination sites. AB - The immunoglobulin heavy chain switch from synthesis of IgM to IgG, IgA or IgE is mediated by a DNA recombination event. Recombination occurs within switch regions, 2-10 kb segments of DNA that lie upstream of heavy chain constant region genes. A compilation of DNA sequences at more than 150 recombination sites within heavy chain switch regions is presented. Switch recombination does not appear to occur by homologous recombination. An extensive search for a recognition motif failed to find such a sequence, implying that switch recombination is not a site specific event. A model for switch recombination that involves illegitimate priming of one switch region on another, followed by error-prone DNA synthesis, is proposed. PMID- 8441649 TI - Cloning, production and characterisation of wild type and mutant forms of the R.EcoK endonucleases. AB - The hsdR, hsdM and hsdS genes coding for R.EcoK restriction endonuclease, both with and without a temperature sensitive mutation (ts-1) in the hsdS gene, were cloned in pBR322 plasmid and introduced into E.coli C3-6. The presence of the hsdSts-1 mutation has no effect on the R-M phenotype of this construct in bacteria grown at 42 degrees C. However, DNA sequencing indicates that the mutation is still present on the pBR322-hsdts-1 operon. The putative temperature sensitive endonuclease was purified from bacteria carrying this plasmid and the ability to cleave and methylate plasmid DNA was investigated. The mutant endonuclease was found to show temperature-sensitivity for restriction. Modification was dramatically reduced at both the permissive and non-permissive temperatures. The wild type enzyme was found to cleave circular DNA in a manner which strongly suggests that only one endonuclease molecule is required per cleavage event. Circular and linear DNA appear to be cleaved using different mechanisms, and cleavage of linear DNA may require a second endonuclease molecule. The subunit composition of the purified endonucleases was investigated and compared to the level of subunit production in minicells. There is no evidence that HsdR is prevented from assembling with HsdM and HsdSts-1 to produce the mutant endonuclease. The data also suggests that the level of HsdR subunit may be limiting within the cell. We suggest that an excess of HsdM and HsdS may produce the methylase in vivo and that assembly of the endonuclease may be dependent upon the prior production of this methylase. PMID- 8441650 TI - Reversion of a transcriptionally defective MHC class II-negative human B-cell mutant. AB - RJ2.2.5, a mutant derived from the human B-lymphoma cell, Raji, is unable to express the MHC class II genes because of a recessive transcriptional defect attributed to the lack of an activator function. We report the isolation of a RJ2.2.5 revertant, namely AR, in which the expression of the mRNAs encoded by these genes is restored. Comparison of the binding of nuclear extracts or of partially purified nuclear preparations from the wild-type, the mutant and the revertant cells to a conserved MHC class II promoter element, the X-box, showed no alteration in the mobility of the complexes thus formed. However, in extracts from RJ2.2.5, and other MHC class II negative cell lines, such as HeLa, the amount of complex observed was significantly higher than in wild-type Raji cells. Furthermore, the binding activity exhibited by the AR revertant was lower than that of the RJ2.2.5 and higher than that of Raji. The use of specific monoclonal antibodies indicated that in all cases c-Jun and c-Fos or antigenically related proteins were required for binding. An inverse correlation between the level of DNA-protein complex formed and the level of MHC class II gene mRNA expressed in the three cell lines was apparent, suggesting that overexpression of a DNA binding factor forming complexes with class II promoter elements may cause repression of MHC class II transcription. A model which reconciles the previously ascertained recessivity of the phenotype of the mutation carried by RJ2.2.5 with the findings reported here is discussed. PMID- 8441651 TI - Mitochondrial genome expression in a mutant strain of D. subobscura, an animal model for large scale mtDNA deletion. AB - A mitochondrial mutant strain of D. subobscura has two mitochondrial genome populations (heteroplasmy): the first (20-30% of the population, 15.9 kb) is the same as could be found in the wild type; the second (70-80% of the population, 11 kb) has lost by deletion several genes coding for complex I and III subunits, and four tRNAs. In human pathology, this kind of mutation has been correlated with severe diseases such as the Kearns-Sayre syndrome, but the mutant strain, does not seem to be affected by the mutation (1). Studies reported here show that: a) Transcripts from genes not concerned by the mutation are present at the same level in both strains. b) In contrast, transcript concentrations from genes involved in the deletion are significantly decreased (30-50%) in the mutant. c) Deleted DNA was expressed as shown by the detection of the fusion transcript. d) The mtDNA/nuc.DNA ratio is 1.5 times higher in the mutant strain than in the wild type. The mutation leads to change in the transcript level equilibrium. The apparent innocuousness of the mutation may suggest some post-transcriptional compensation mechanisms. This drosophila strain is an interesting model to study the consequence of this type of mitochondrial genome deletion. PMID- 8441652 TI - The use of bidirectional transcription footprinting to detect platinum-DNA crosslinks by acridine-tethered platinum diamine complexes and cisplatin. AB - Bidirectional transcription footprinting has been used to probe the platination of DNA by cisplatin, and to examine the modulation of these interactions by (a) cyclisation of the non-reactive amino group by either ethyl or propyl groups, and (b) the further addition of a pendant intercalator (9-amino acridine) linked by either phenylethyl or phenylpentyl groups. Intrastrand crosslinking was detected for all derivatives at all 5'-GG and 5'-AG sequences on the template strand, but the same sites did not result in transcriptional blockages when on the non template strand. There was little effect of cyclysation of the amino groups, but the further addition of an intercalator resulted in three responses: a time dependent increase of the blocked transcript by one and three nucleotides; a reduction of the sequence selectivity of platination; a decrease of apparent interstrand crosslinking for these derivatives with a pendant intercalator tethered to the amino moiety of cisplatin. PMID- 8441654 TI - Pleiotrophic effects of point mutations in yeast tRNA(Asp) on the base modification pattern. AB - The base-modification pattern has been studied in several synthetic variants of yeast tRNA(Asp) injected into Xenopus laevis oocytes. Certain point mutations in the D-stem and the variable loop of the tRNA led to considerably decreased levels of m1G37, psi 40 and Q34/manQ34 in the anticodon stem or loop and an increased rate of synthesis for m5C49 in the T-stem. The formation of m2G6 in the aminoacyl stem was not affected in any of the tRNA-variants. Thus, mutations in one part of the tRNA-molecule can have long-range effects on the interactions between another part of the tRNA and the tRNA modifying enzymes. PMID- 8441653 TI - Targeted recombination with single-stranded DNA vectors in mammalian cells. AB - We studied the ability of single-stranded DNA (ssDNA) to participate in targeted recombination in mammalian cells. A 5' end-deleted adenine phosphoribosyltransferase (aprt) gene was subcloned into M13 vector, and the resulting ssDNA and its double-stranded DNA (dsDNA) were transfected to APRT Chinese hamster ovary cells with a deleted aprt gene. APRT+ recombinants with the ssDNA was obtained at a frequency of 3 x 10(-7) per survivor, which was almost equal to that with the double-stranded equivalent. Analysis of the genome in recombinant clones produced by ssDNA revealed that 12 of 14 clones resulted from correction of the deletion in the aprt locus. On the other hand, the locus of the remaining 2 was not corrected; instead, the 5' deletion of the vector was corrected by end extension, followed by integration into random sites of the genome. To exclude the possibility that input ssDNA was converted into its duplex form before participating in a recombination reaction, we compared the frequency of extrachromosomal recombination between noncomplementary ssDNAs, and between one ssDNA and one dsDNA, of two phage vectors. The frequency with the ssDNAs was 0.4 x 10(-5), being 10-fold lower than that observed with the ssDNA and the dsDNA, suggesting that as little as 10% of the transfected ssDNA was converted into duplex forms before the recombination event, hence 90% remained unchanged as single-stranded molecules. Nevertheless, the above finding that ssDNA was as efficient as dsDNA in targeted recombination suggests that ssDNA itself is able to participate directly in targeted recombination reactions in mammalian cells. PMID- 8441655 TI - Formation of AraC-DNA sandwiches. AB - With the use of special DNA binding sites, but not the natural aral binding site, the dimeric AraC protein can be forced to make sandwich structures in which two DNA molecules are joined by two AraC protein dimers. Apparently one subunit from each dimer contacts each DNA molecule in an extended structure. These sandwich structures form only in the absence of arabinose. This behavior is consistent with the protein's ability to form DNA loops by binding to separated half sites in the absence of arabinose and its preference for binding to adjacent half-sites in the presence of arabinose. PMID- 8441656 TI - The human hnRNP M proteins: identification of a methionine/arginine-rich repeat motif in ribonucleoproteins. AB - Recent reports indicate that proteins which directly bind to nascent RNA polymerase II transcripts, the heterogeneous nuclear ribonucleoproteins (hnRNPs), play an important role in both transcript-specific packaging and alternative splicing of pre-mRNAs. Here we describe the isolation and characterization of a group of abundant hnRNPs, the M1-M4 proteins, which appear as a cluster of four proteins of 64,000-68,000 daltons by two-dimensional electrophoresis. The M proteins are pre-mRNA binding proteins in vivo, and they bind avidly to poly(G) and poly(U) RNA homopolymers in vitro. Covalently associated polyadenylated RNA protein complexes, generated by irradiating living HeLa cells with UV light, were purified and used to elicit antibodies in mice. The resulting antisera were then employed to isolate cDNA clones for the largest M protein, M4, by immunological screening. The deduced amino acid sequence of M4 indicates that the M proteins are members of the ribonucleoprotein consensus sequence family of RNA-binding proteins with greatest similarity to a hypothetical RNA-binding protein from Saccharomyces cerevisiae. The M proteins also possess an unusual hexapeptide repeat region rich in methionine and arginine residues (MR repeat motif) that resembles a repeat in the 64,000 dalton subunit of cleavage stimulation factor, which is involved in 3'-end maturation of pre-mRNAs. Proteins immunologically related to M exist in divergent eukaryotes ranging from human to yeast. PMID- 8441657 TI - Presence of an inhibitor of RNA polymerase I mediated transcription in extracts from growth arrested mouse cells. AB - Extracts obtained from mouse cells growth arrested at stationary phase or under serum starvation exhibit no specific rDNA transcription activity. Experiments with mixed transcriptionally active and inactive whole cell extracts (WCE) obtained from rapidly dividing or growth arrested cells, respectively, demonstrate that rRNA synthesis in vitro can be suppressed by a polymerase I transcription inhibitory activity (PIN), present in inactive extracts. This inhibition effect is not related to increased nuclease activity and affects neither the non-specific Pol I transcription, nor a polymerase II promoter. A comparison of WCE isolated under different growth conditions indicates that PIN changes according to the physiological state of the cell. It reaches a maximal level soon after serum depletion and disappears rapidly when cells are allowed to recover in serum-rich medium. PIN can be clearly demonstrated in WCE but not in nuclear or cytoplasmic extracts and can be also obtained by an additional high salt extraction of nuclei. Furthermore, gel retardation and transcription-in pellet assays demonstrate that rDNA promoter binding and preinitiation complex stability are similar in active and inactive WCE. This indicates that some later stage(s) of rDNA transcription, rather than the preinitiation complex formation, are attenuated by inactive extracts. Analysis of partially fractionated extracts suggests that PIN is not associated with but can be separated from polymerase I. PMID- 8441659 TI - The helical repeat of DNA at high temperature. AB - The increasing number of studies on thermophilic organisms addressed the question of DNA double helix parameters at high temperature. The present study shows that the helix rotation angle per base pair omega of an unconstrained DNA decreases linearly upon temperature increase, up to the premelting range. In the ionic conditions tested, this rule extends to temperatures up to 85 degrees C, which is a common growth temperature for many hyperthermophilic organisms. In addition, the torsional constant K of DNA decreases with temperature, indicating that the energy required to modify the DNA twist is lower at high temperature. These findings have several implications for people working on the structure and enzymology of DNA at high temperature. PMID- 8441658 TI - Functional analysis of the human neurofilament light chain gene promoter. AB - We have carried out a structural and functional analysis on the human NF-L (H-NF L) gene. It contains a methylation-free island, spanning the 5' flanking sequences and the first exon and a number of neuronal-specific DNase I hypersensitive sites have been identified in the upstream region as well as within the body of the gene. Analysis in cell lines and transgenic mice using a combination of these sites has revealed the presence of a conserved element(s) between -300bp and -190bp which is required for neuronal-specific expression. PMID- 8441660 TI - Cloning and sequence determination of the Schizosaccharomyces pombe rpb2 gene encoding the subunit 2 of RNA polymerase II. AB - The gene, rpb2, encoding the second largest subunit, subunit 2, of RNA polymerase II has been cloned from Schizosaccharomyces pombe using the corresponding gene, RPB2, of Saccharomyces cerevisiae as a probe for cross-hybridization. We have determined the complete nucleotide sequence of rpb2, and parts of the PCR amplified rpb2 cDNA. The predicted coding sequence of a polypeptide of 1210 amino acid residues with a calculated molecular weight of 138 kilodaltons was interrupted by a short intron. The overall amino acid sequence homology of the S. pombe subunit 2 is 68, 62 and 62% with the corresponding protein from S. cerevisiae, D. melanogaster and H. sapiens, respectively. Southern analysis of the genomic DNA digested with various restriction enzymes showed that rpb2 was present as a single copy in the S. pombe genome. Northern analysis showed that the transcript of rpb2 was about 4 kb in length. PMID- 8441662 TI - An alternative approach to 32P radiation protection: source shielding. AB - 32P is the most widely used isotope in molecular biology laboratories and a high energy beta-emitter. Local doses are often underestimated and plexiglass shielding converts some energy into penetrating gamma radiation. We describe a series of equipment that reduces local doses and gamma radiation more efficiently than traditional equipment and at the same time facilitates the handling of the isotopes. PMID- 8441661 TI - Zebrafish pou[c]: a divergent POU family gene ubiquitously expressed during embryogenesis. AB - We report the isolation and characterization of cDNA for a novel zebrafish (Brachyodanio rerio) POU domain gene, pou[c], which is ubiquitously expressed during embryonic development. This gene encodes a 610 amino acids long protein with a 149 amino acid POU domain ending only 8 residues before the C terminus. The 453 amino acids long region N-terminal to the POU domain contains several features typical of transcriptional activation domains such as an acidic region with a putative amphipathic alpha-helix, a glutamine-rich region, and short threonine- and/or serine-rich regions. Comparison of the POU domain of pou[c] to other known POU sequences clearly show that pou[c] has the most divergent POU domain sequence reported to date. Thus, we suggest that pou[c] should be placed as the presently sole member of a new, sixth class of POU proteins. DNA-binding studies revealed that pou[c] is not an octamer-binding transcription factor like the Oct proteins described from mammals, chicken and Xenopus. Rather, pou[c] binds with high affinity to the TAATGARAT motif found in the promoters of the herpes simplex virus immediate early genes and to degenerate octamer-TAATGA motifs. Circular permutation analyses also show that pou[c] induces DNA bending upon sequence-specific binding. PMID- 8441663 TI - Isolation of telomeric DNA from the filamentous fungus Podospora anserina and construction of a self-replicating linear plasmid showing high transformation frequency. AB - It has been previously shown that linear plasmids bearing Tetrahymena telomeric sequences are able to replicate autonomously in the filamentous fungus Podospora anserina (1). However, autonomous replication occurs in only 50-70% of the transformants, suggesting a defect in the recognition of the Tetrahymena telomeric template by the putative P. anserina telomerase so that only a fraction of entering DNA is stabilized into linear extrachromosomal molecules. We have cloned DNA sequences added to the Tetrahymena (T2G4)n ends of the linear plasmid. Nucleotide sequencing showed that these sequences are exclusively composed of T2AG3 repeat units. Hybridization experiments of Bal31 treated DNA showed that T2AG3 repeats are confined within 200 bp in chromosomal P. anserina telomeres. A new plasmid has been constructed so that after linearization, the terminal sequences contain T2AG3 repeats. This linear molecule transforms P. anserina with a high frequency (up to 1.75 x 10(4) transformants/micrograms), autonomous replication occurs in 100% of the transformants and the plasmid copy number is about 2-3 per nucleus. These results underscore the importance of the telomeric repeat nucleotide sequence for efficient recognition as functional telomeric DNA in vivo and provide the first step toward the development of an artificial chromosome cloning system for filamentous fungi. PMID- 8441664 TI - Atomic force microscopy of DNA in aqueous solutions. AB - DNA on mica can be imaged in the atomic force microscope (AFM) in water or in some buffers if the sample has first been dehydrated thoroughly with propanol or by baking in vacuum and if the sample is imaged with a tip that has been deposited in the scanning electron microscope (SEM). Without adequate dehydration or with an unmodified tip, the DNA is scraped off the substrate by AFM-imaging in aqueous solutions. The measured heights and widths of DNA are larger in aqueous solutions than in propanol. The measured lengths of DNA molecules are the same in propanol and in aqueous solutions and correspond to the base spacing for B-DNA, the hydrated form of DNA; when the DNA is again imaged in propanol after buffer, however, it shortens to the length expected for dehydrated A-DNA. Other results include the imaging of E. coli RNA polymerase bound to DNA in a propanol-water mixture and the observation that washing samples in the AFM is an effective way of disaggregating salt-DNA complexes. The ability to image DNA in aqueous solutions has potential applications for observing processes involving DNA in the AFM. PMID- 8441665 TI - Oncogenic conversion of Ets affects redox regulation in-vivo and in-vitro. AB - The avian acute leukemia virus E26 encodes a fusion protein between viral Gag and the cellular transcription factors cMyb and cEts1(p68). vEts on its own transforms more mature erythroid cells. We have compared the properties of vEts and cEts1(p68). vEts interacts preferentially with an antibody that recognizes the active conformation of the DNA-binding domain. The DNA-binding activity of vEts is particularly sensitive to incubation conditions for band-shift assays, phosphorylation and modification by sulphydryl-specific reagents. Increased sensitivity is due to loss of a protective function of cEts1 C-terminal sequences. cEts2 has a related C-terminal sequence with a similar role. These results suggest that the vEts DNA-binding domain is more accessible to protein protein interactions and to regulatory mechanisms. Indeed, vEts DNA binding is preferentially inactivated by oxidizing conditions in-vivo. We suggest that the 'open' conformation of the vEts DNA-binding domain favours interactions with other proteins or DNA and facilitates transformation. PMID- 8441667 TI - Ease of DNA unwinding is a conserved property of yeast replication origins. AB - Autonomously replicating sequence (ARS) elements function as plasmid replication origins. Our studies of the H4 ARS and ARS307 have established the requirement for a DNA unwinding element (DUE), a broad easily-unwound sequence 3' to the essential consensus that likely facilitates opening of the origin. In this report, we examine the intrinsic ease of unwinding a variety of ARS elements using (1) a single-strand-specific nuclease to probe for DNA unwinding in a negatively-supercoiled plasmid, and (2) a computer program that calculates DNA helical stability from the nucleotide sequence. ARS elements that are associated with replication origins on chromosome III are nuclease hypersensitive, and the helical stability minima correctly predict the location and hierarchy of the hypersensitive sites. All well-studied ARS elements in which the essential consensus sequence has been identified by mutational analysis contain a 100-bp region of low helical stability immediately 3' to the consensus, as do ARS elements created by mutation within the prokaryotic M13 vector. The level of helical stability is, in all cases, below that of ARS307 derivatives inactivated by mutations in the DUE. Our findings indicate that the ease of DNA unwinding at the broad region directly 3' to the ARS consensus is a conserved property of yeast replication origins. PMID- 8441666 TI - Isolation of a cDNA encoding the adenovirus E1A enhancer binding protein: a new human member of the ets oncogene family. AB - The cDNA encoding adenovirus E1A enhancer-binding protein E1A-F was isolated by screening a HeLa cell lambda gt11 expression library for E1A-F site-specific DNA binding. One cDNA clone produced recombinant E1A-F protein with the same DNA binding specificity as that endogenous to HeLa cells. Sequence analysis of the cDNA showed homology with the ETS-domain, a region required for sequence-specific DNA binding and common to all ets oncogene members. Analysis of the longest cDNA revealed about a 94% identity in amino acids between human E1A-F and mouse PEA3 (polyomavirus enhancer activator 3), a recently characterized ets oncogene member. E1A-F was encoded by a 2.5kb mRNA in HeLa cells, which was found to increase during the early period of adenovirus infection. In contrast, ets-2 mRNA was significantly reduced in infected HeLa cells. The results indicate that E1A enhancer binding protein E1A-F is a member of the ets oncogene family and is probably a human homologue of mouse PEA3. PMID- 8441668 TI - BI-BII transitions in B-DNA. AB - Molecular modelling is used to study the conformational and energetic aspects of BI-BII transitions within the backbone of a B-DNA dodecamer d(CATGACGTCATG) whose fine structure has previously been determined by molecular modelling combined with NMR spectroscopy. It is shown that while the dodecamer under investigation does not contain any BII junctions, the central CpG step can most easily undergo the transition. More generally, it is also found that the base sequence and hence the backbone geometry of a DNA segment, strongly influences both the conformational impact of the transition, the associated energy barrier and the stability of the resulting BII state. PMID- 8441669 TI - Conformation of d(GGGATCCC)2 in crystals and in solution studied by X-ray diffraction, Raman spectroscopy and molecular modelling. AB - In the crystal, d(GGGATCCC)2 forms an A-DNA double helix as known from a single crystal X-ray diffraction study. Accordingly, in the Raman spectra of crystals the A-family marker bands at 664, 705, 807 and 1101 cm-1 and the spectral characteristics in the region 1200 to 1500 cm-1 clearly demonstrate the A-form as the dominant conformation. Bands at 691, 850, and 1080 cm-1, however, indicate that a minor fraction of the octamer molecules in the crystal is in an unusual, still not unequivocally identified conformation possibly belonging to the B family. In solution, the octamer is in B-like conformation as shown by the presence of B-DNA Raman marker bands at 685, 837, 1094 and 1421 cm-1. Molecular modelling techniques lead to three structures with slightly different B-form geometries as the lowest energies models when a sigmoidal dielectric function with the bulk dielectric constant epsilon = 78 and the value q = -0.5e for the effective phosphate charges was used in the calculations. An A-form structure bearing a strong resemblance to the experimentally determined crystal structure becomes the lowest energy model structure when the electrostatic parameters are changed to epsilon = 30 and q = -0.25e, respectively. PMID- 8441670 TI - Quantitative titration of nucleic acids by enzymatic amplification reactions run to saturation. AB - In vitro enzymatic amplification of nucleic acids by PCR or other techniques is a very sensitive method to detect rare DNA segments. We present here a protocol that allows the rapid, sensitive and precise quantification of DNA molecules using PCR amplification run to saturation. The DNA (or cDNA) to be assayed is co amplified with known amounts of an internal standard DNA. We show that the latter must be almost identical to the assayed DNA, otherwise quantification at the plateau is unreliable. The read-out of the amplification involves one or two additional oligonucleotides. Using fluorescent oligonucleotides as primers in run off reactions together with an automated DNA sequencer, we could measure the level of expression of several genes, like the murine MHC class I H-2Kd or a specific T cell receptor beta chain transcript in the course of an immunization. mRNA levels were normalized by measuring in a similar manner the number of transcripts encoding the housekeeping gene HPRT. Finally, our procedure might allow the rapid analysis of a large number of samples at the same time, as illustrated by the simultaneous analysis of the mRNAs encoding the CD4 and CD8 murine T cell markers. PMID- 8441671 TI - Effect of a 5'-phosphate on the stability of triple helix. AB - An effect of 5'-phosphorylation on the stability of triple helical DNA containing pyrimidine:purine:pyrimidine strands has been demonstrated by both gel electrophoresis and UV melting. A 5'-phosphate on the purine-rich middle strand of a triple helix lowers the stability of triple helix formation by approximately 1 kcal/mol at 25 degrees C. The middle strand is involved in both Watson-Crick and Hoogsteen base pairing. In contrast, a 5'-phosphate on the pyrimidine-rich strands, which are involved in either Watson-Crick or Hoogsteen base pairing, has a smaller effect on the stability of triple helix. The order of stability is: no phosphate on either strand > phosphate on both pyrimidine strands > phosphate on purine strand > phosphate on all three strands. Differential stability of triple helix species is postulated to stem from an increase in rigidity due to steric hindrance from the 5'-phosphate. This result indicates that labelling with 32P affect equilibrium in triplex formation. PMID- 8441672 TI - Identification of coding regions in genomic DNA sequences: an application of dynamic programming and neural networks. AB - Dynamic programming (DP) is applied to the problem of precisely identifying internal exons and introns in genomic DNA sequences. The program GeneParser first scores the sequence of interest for splice sites and for these intron- and exon specific content measures: codon usage, local compositional complexity, 6-tuple frequency, length distribution and periodic asymmetry. This information is then organized for interpretation by DP. GeneParser employs the DP algorithm to enforce the constraints that introns and exons must be adjacent and non overlapping and finds the highest scoring combination of introns and exons subject to these constraints. Weights for the various classification procedures are determined by training a simple feed-forward neural network to maximize the number of correct predictions. In a pilot study, the system has been trained on a set of 56 human gene fragments containing 150 internal exons in a total of 158,691 bps of genomic sequence. When tested against the training data, GeneParser precisely identifies 75% of the exons and correctly predicts 86% of coding nucleotides as coding while only 13% of non-exon bps were predicted to be coding. This corresponds to a correlation coefficient for exon prediction of 0.85. Because of the simplicity of the network weighting scheme, generalization performance is nearly as good as with the training set. PMID- 8441673 TI - Molecular cloning, sequence, structural analysis and expression of the histidyl tRNA synthetase gene from Streptococcus equisimilis. AB - The histidyl-tRNA synthetase gene (hisS) from Streptococcus equisimilis was cloned and sequenced. The gene for this aminoacyl-tRNA synthetase has an open reading frame of 1278 nucleotides. The deduced amino acid sequence encodes a protein of 426 amino acids with MW = 47,932. The protein is predicted to be soluble with a pl = 5.27. The protein sequence has extensive overall identity/similarity with the Escherichia coli and the yeast histidyl-tRNA synthetases (approximately 58% and approximately 20%, respectively). A putative promoter for gene transcription lies within two hundred nucleotides of the polypeptide start codon. The enzyme was overexpressed, to a level of about 18% of total cellular protein, as a fusion protein (containing an additional 15 amino acids) in E. coli using the pT7 expression system containing the T7 RNA polymerase/promoter (Tabor and Richardson, Proc. Natl. Acad. Sci. U.S.A. 82:1074 1078, 1985). The predicted MW for the hisS gene product is in good agreement with the size of the fusion protein determined by SDS-PAGE (M(r) = 53,700). Amino acid sequencing of the intact fusion protein and proteolytic fragments confirmed the deduced sequence of the synthetase at many positions throughout the protein. The expressed protein catalyzed the specific aminoacylation of tRNA(His) in vitro. PMID- 8441674 TI - Erythromycin and 5S rRNA binding properties of the spinach chloroplast ribosomal protein CL22. AB - The spinach chloroplast ribosomal protein (r-protein) CL22 contains a central region homologous to the Escherichia coli r-protein L22 plus long N- and C terminal extensions. We show in this study that the CL22 combines two properties which in E. coli ribosome are split between two separate proteins. The CL22 which binds to the 5S rRNA can also be linked to an erythromycin derivative added to the 50S ribosomal subunit. This latter property is similar to that of the E. coli L22 and suggests a similar localization in the 50S subunit. We have overproduced the r-protein CL22 and deleted forms of this protein in E. coli. We show that the overproduced CL22 binds to the chloroplast 5S rRNA and that the deleted protein containing the N- and C-terminal extensions only has lost the 5S rRNA binding property. We suggest that the central homologous regions of the CL22 contains the RNA binding domain. PMID- 8441675 TI - The adenovirus DNA binding protein effects the kinetics of DNA replication by a mechanism distinct from NFI or Oct-1. AB - Initiation of adenovirus DNA replication in vitro minimally requires the viral TP DNA template and the precursor terminal protein-DNA polymerase heterodimer (pTP pol). Optimal initiation occurs in the presence of the cellular transcription factors NFI and Oct-1 and the viral DNA binding protein (DBP). We have studied the influence of these three stimulatory proteins on the kinetics of formation of the pTP-dCMP initiation complex. NFI increases the Vmax of the reaction but does not affect the apparent Km for dC-TP. This indicates that NFI acts by enlarging the amount of active initiation complex in agreement with its stabilizing effect on binding of pTP-pol to the template. Similar kinetic effects were observed for Oct-1. Since Oct-1 does not stabilize binding of pTP-pol to the origin this suggests that Oct-1 increases the rate of pTP-dCMP formation. DBP stimulates the initiation reaction in two ways. First, it moderately increases the Vmax at suboptimal NFI concentrations, which is related to its enhancing effect on binding of NFI to the origin. Second, a much larger stimulation was caused by DBP itself based on a reduction of the Km for dCTP, which was independent of the concentration of pTP-pol or NFI. The Km for dCTP during initiation is lower than during elongation. PMID- 8441676 TI - Zinc finger-like motifs in rat ribosomal proteins S27 and S29. AB - The primary structures of the rat 40S ribosomal subunit proteins S27 and S29 were deduced from the sequences of nucleotides in recombinant cDNAs and confirmed by determination of amino acid sequences in the proteins. Ribosomal protein S27 has 83 amino acids and the molecular weight is 9,339. Hybridization of cDNA to digests of nuclear DNA suggests that there are 4-6 copies of the S27 gene; the mRNA for the protein is about 620 nucleotides in length. Ribosomal protein S29 has 55 amino acids and the molecular weight is 6,541. There are 14-17 copies of the S29 gene and its mRNA is about 500 nucleotides in length. Rat ribosomal protein S29 is related to several members of the archaebacterial and eubacterial S14 family of ribosomal proteins. S27 and S29 have zinc finger-like motifs as do other proteins from eukaryotic, archaebacterial, eubacterial, and mitochondrial ribosomes. Moreover, ribosomes and ribosomal subunits appear to contain zinc and iron as well. PMID- 8441677 TI - Restriction endonuclease cleavage of 5-methyl-deoxycytosine hemimethylated DNA at high enzyme-to-substrate ratios. AB - We have investigated the ability of a large number of restriction enzymes to digest non-canonically hemimethylated DNA at high enzyme-to-substrate ratios. A single-stranded unmethylated phagemid was used as a template to complete synthesis of the second strand using 5-methyl-dCTP to substitute for all the deoxycytosine residues. A fragment of this double-stranded hemimethylated DNA which contains the multiple cloning site region was used as a substrate. For all the enzymes tested, at least some degree of protection from digestion is observed. Sites completely protected from digestion by their cognate enzymes are SalI, BstXI, SacI, SacII, SmaI, SstI, XhoI, PstI, HinfI, BamHI and AccI. Sites partially protected from digestion by their cognate enzymes are XbaI, HindIII, KpnI, SpeI, ClaI, EcoRI and PvuII. Knowledge of the sensitivity of commonly used restriction enzymes to hemimethylated substrates is useful for several applications, which will be discussed. PMID- 8441678 TI - Identification of a cis acting element responsible for muscle specific expression of the c-mos protooncogene. AB - A series of deletion constructs of the 5' flanking region of rat c-mos gene was positioned upstream to the CAT gene and transfected into muscle and non-muscle cells. CAT activities revealed that a region located downstream of a TATA box and containing the proximal transcription start site is the muscle c-mos promoter. This promoter is more efficient in L6 alpha 1 myoblasts than in L6 alpha 1 myotubes but not in C3H10T1/2 cells. Gel shift assays demonstrated that nuclear proteins from myoblasts and myotubes formed complexes migrating differently. Footprinting analyses showed that nuclear proteins from L6 alpha 1 myoblasts protected a DNA fragment located at position nt -979 to nt -938 relative to the first ATG of the rat c-mos ORF while nuclear proteins from myotubes protected the DNA between nt -998 to nt -928. Furthermore one of protein - DNA complexes containing the proximal transcription start site, included a consensus sequence TGTC(AGT/TCG)CC(A/T)G present in the initiator element (Inr) of several genes. Southwestern blot analysis pointed to a 82kDa polypeptide as a potential candidate for trans acting factor in myoblasts. In L6 alpha 1 myotubes this polypeptide is replaced by other proteins of 40-42kDa and 82kDa. An interplay between these two complexes may constitute a developmental as well as a physiologically regulated mechanism that modulates c-mos expression during the early stages of myogenesis. PMID- 8441679 TI - Assessments of DNA inhomogeneities in yeast chromosome III. AB - With the sequencing of the first complete eukaryotic chromosome, III of yeast (YCIII) of length 315 kb, several types of questions concerning chromosomal organization and the heterogeneity of eukaryotic DNA sequences can be approached. We have undertaken extensive analysis of YCIII with the goals of: (1) discerning patterns and anomalies in the occurrences of short oligonucleotides; (2) characterizing the nature and locations of significant direct and inverted repeats; (3) delimiting regions unusually rich in particular base types (e.g., G+C, purines); and (4) analyzing the distributions of markers of interest, e.g., delta (delta) elements, ARS (autonomous replicating sequences), special oligonucleotides, close repeats and close dyad pairings, and gene sequences. YCIII reveals several distinctive sequence features, including: (i) a relative abundance of significant local and global repeats highlighting five genes containing substantial close or tandem DNA repeats; (ii) an anomalous distribution of delta elements involving two clusters and a long gap; (iii) a significantly even distribution of ARS; (iv) a relative increase in the frequency of T runs and AT iterations downstream of genes and A runs upstream of genes; and (v) two regions of complex repetitive sequences and anomalous DNA composition, 29000-31000 and 291000-295000, the latter centered at the HMRa locus. Interpretations of these findings for chromosomal organization and implications for regulation of gene expression are discussed. PMID- 8441680 TI - Structure of the rat p53 tumor suppressor gene. AB - Aberration within the p53 tumor suppressor gene is the most frequently identified genetic damage in human cancer. Regulatory functions proposed for the p53 protein include modulation of the cell cycle, cellular differentiation, signal transduction, and gene expression. Additionally, the p53 gene product may guard the genome against incorporation of damaged DNA. To facilitate study of its role in carcinogenesis using a common animal model, we determined the structure of the rat p53 gene. We identified 18 splice sites and defined 25 bases of the intervening sequences adjacent to these sites. We also discovered an allelic polymorphism that occurs within intron 5 of the gene. The rat gene approximates the mouse ortholog. It is 12 kb in length with the non-coding exon 1 separated from exon 2 by 6.2 kb of intervening sequence. The location and size of all rat gene introns approximate those of the mouse. Whereas the mouse and human genes each contain 11 exons, the rat p53 gene is composed of only 10. No intervening sequence occurs between the region of the rat gene corresponding to exons 6 and 7 of the mouse and human p53 genes. This implies intron 6 may be functionally insignificant for species in which it is retained. To extrapolate to p53 involvement in human tumorigenesis, we suggest that mutational events within intron 6 may not be of pathological significance unless splicing is hindered. PMID- 8441681 TI - Structure/function analysis of the Ala116-->Lys121 region of endonuclease V by random targeted mutagenesis. AB - Endonuclease V is the product of the denV gene of bacteriophage T4 and is responsible for the recognition and repair of pyrimidine dimers due to UV irradiation of DNA. This is accomplished by a two-step mechanism involving incision at the site of the lesion followed by cleavage of the phosphate backbone. In order to better understand this molecule, and to validate our new mutagenesis procedure, we have constructed a series of random mutations within the region Ala116-->Lys121 using a random targeted mutagenesis procedure developed for this study. The results presented here suggest an important role for this region in the stabilization of the thymine dimer-containing substrate. These mutants also confirm a direct correlation between survival and both DNA binding and pyrimidine dimer-DNA glycosylase activity. No such correlation exists between survival and AP lyase activity. The results are consistent with the recently published X-ray crystal structure. PMID- 8441682 TI - Quantitative sequence-activity models (QSAM)--tools for sequence design. AB - Models have been developed that allow the biological activity of a DNA segment to be altered in a desired direction. Partial least squares projections to latent structures (PLS) was used to establish a quantitative model between a numerical description of 68 bp fragments of 25 E.coli promoters and their corresponding quantitative measure of in vivo strength. This quantitative sequence-activity model (QSAM) was used to generate two 68 bp fragments predicted to be more potent promoters than any of those on which the model originally was based. The optimized structures were experimentally verified to be strong promoters in vivo. PMID- 8441683 TI - Nucleotide sequence of a Trichoderma longibrachiatum DNA fragment encoding the 5.8S rRNA gene. PMID- 8441684 TI - Nucleotide sequence of the cDNA encoding silk gland elongation factor 1 alpha. PMID- 8441686 TI - Seven new members of the Sox gene family expressed during mouse development. PMID- 8441685 TI - Elongation factor 1 contains two homologous guanine-nucleotide exchange proteins as shown from the molecular cloning of beta and delta subunits. PMID- 8441687 TI - The human homolog of ribosomal protein S18. PMID- 8441688 TI - DNA sequence and shuttle vector construction of plasmid pGL3 from Plectonema boryanum PCC 6306. PMID- 8441690 TI - The primary structure of human ribosomal protein L12. PMID- 8441689 TI - Striking homology between mouse and human transcription enhancer factor-1 (TEF 1). PMID- 8441691 TI - Reassessment of the murine c-fms proto-oncogene sequence. PMID- 8441692 TI - Lactobacillus casei contains a member of the CRP-FNR family. PMID- 8441693 TI - Single-step piperidine elution, cleavage, and recovery of premodified DNA electrotransferred on NA-45 membrane from mobility-shift gels. PMID- 8441694 TI - Localisation of DNA-protein contact points by DMS resistance of complexes resolved in gel retardation assays. PMID- 8441696 TI - DNA fingerprinting of Mycobacterium tuberculosis isolates by ligation-mediated polymerase chain reaction. PMID- 8441695 TI - Direct quantification of specific mRNA using a selected biotinylated oligonucleotide by free solution capillary electrophoresis. PMID- 8441697 TI - Sex determination by low stringency PCR (LS-PCR). PMID- 8441698 TI - Extension of yeast artificial chromosomes by cosmid multimers. PMID- 8441700 TI - Efficient DNA transfection of quiescent mammalian cells using poly-L-ornithine. PMID- 8441699 TI - Exon mapping by PCR. PMID- 8441701 TI - Efficient cloning of fragments of the polymerase chain reaction directly into the single stranded bacteriophage M13mp18. PMID- 8441702 TI - Efficient random mutagenesis method with adjustable mutation frequency by use of PCR and dITP. PMID- 8441703 TI - Non-radioactive analysis of multiplexed microsatellite reactions using a direct blotting-sequencing apparatus. PMID- 8441704 TI - Silicone lubricant enhances recovery of nucleic acids after phenol-chloroform extraction. PMID- 8441705 TI - A 'one tube reaction' for synthesis and amplification of total cDNA from small numbers of cells. PMID- 8441706 TI - Immunosuppressive activity in the series of cycloamanide peptides from mushrooms. AB - The immunosuppressor activity of the cycloamanides A, B, C, and D, and two of their D-amino acid residue-containing analogues, was examined using PFC (plaque forming cell) and DTH (delayed type hypersensitivity) tests. It was found that cycloamanide A (CyA A, II) [c-(Phe-Phe-Ala-Gly-Pro-Val-)] and its D-Phe containing analogue III [c-(Phe-D-Phe-Ala-Gly-Pro-Val-)] are the most potent immunosuppressors of the whole series. The retroanalogue of III [c-(D-Phe-Val-Pro Gly-Ala-)] was found to be less active than III. The immunosuppressor activity of O-carboxymethyl-Tyr6-antamanide (I) was also tested. It was found that the substitution of one of the Phe residues of ANT by O-carboxymethyl-Tyr does not substantially affect the immunosuppressor activity. PMID- 8441707 TI - Cytochemical characterization of anterior pituitary target cells for the neuropeptide, pituitary adenylate cyclase activating polypeptide (PACAP), using biotinylated ligands. AB - Two novel peptides, named PACAP (pituitary adenylate cyclase activating polypeptide) containing 38 (PACAP38) and 27 residues (PACAP27) were recently isolated from ovine hypothalami. In order to investigate the pituitary cell type(s) that bear a receptor for PACAP, PACAP38 was biotinylated and used for cytochemical examination of binding. The cells were also identified by immunocytochemical methods using the antisera against each of the rat anterior pituitary hormones or an antiserum against S-100 protein, a marker for pituitary folliculo-stellate (FS) cells. Biotinylated PACAP38 (biot-PACAP) exhibited adenylate cyclase stimulating activity (ACSA) comparable to PACAP38 in rat pituitary cell cultures, and displaced the bound 125I-PACAP27 to the rat pituitary membrane preparation to the same extent as PACAP38. After 2-4 days of culture, dispersed rat pituitary cells were incubated with varying concentrations of biot-PACAP at room temperature or 4 degrees C. The bound biot-PACAP38 was visualized by avidin-biotin-peroxidase complex (ABC) method with nickel intensification. Biot-PACAP-positive and pituitary hormone or S-100-positive cells were counted. More than 90% of S-100-positive cells bound biot-PACAP38. A considerable number of GH and PRL cells and a lesser number of ACTH cells also bound biot-PACAP38, whereas only a few identified LH, FSH, or TSH cells bound biot-PACAP38. These results suggest that FS cells are a major target cell type for PACAP. A recent study from our laboratory demonstrated that PACAP stimulated the release of interleukin (IL)-6 in rat pituitary cell cultures. FS cells are known to produce IL-6. PMID- 8441708 TI - Effects of anti-CCK-8 antiserum on acquisition and retrieval by mice in an appetitive task. AB - Endogenous cholecystokinin (CCK) was blocked in the posterior cingulate cortex of BALB/c mice using a local injection of anti-CCK-8 antiserum, and memory effects were tested using Go-No Go visual discrimination conditioning. Injection of 0.4 microliter of anti-CCK-8 antiserum diluted to 1:10, 10-15 min before each session, produced substantial learning impairment on the discrimination task. But when injections were stopped, animals began to learn the task normally, showing that the anti-CCK antiserum effect was reversible. When the antiserum was administered at the same dose before a single test session 14 days after the end of the initial training, the retrieval process was also disturbed. These results show that cingulate cholecystokinin is essential for memory processes and suggest that cholecystokinin octapeptide may be a neuromodulator of the thalamo-cingulate pathway of Papez's circuit, which is involved in memory processes. PMID- 8441709 TI - Primary structure of the major isomorph of the crustacean hyperglycemic hormone (CHH-I) from the sinus gland of the Mexican crayfish Procambarus bouvieri (Ortmann): interspecies comparison. AB - The amino acid sequence of this neuropeptide was elucidated by means of a combined approach of enzymatic digestions, manual and automatic Edman degradations, and mass spectrometry. It is a 72 residue peptide (molecular mass 8388 Da), with six cysteines forming three disulfide bridges connecting residues 7-43, 23-39, and 26-52, with blocked N- and C-termini, and lacking the amino acids histidine, methionine, and tryptophan. The CHH-I of Procambarus bouvieri is compared with the other known CHHs from Orconectes limosus (98.6% identity), Homarus americanus isomorph A (83.3% identity), Homarus americanus isomorph B (79.2% identity), and Carcinus maenas (61.1% identity). PMID- 8441711 TI - An owner's manual for total joint replacements. PMID- 8441710 TI - Dorsal raphe nucleus efferents: termination in peptidergic fields. AB - This study was performed to identify the efferents of the dorsal raphe nucleus (DRN), particularly in regard to nociception. Phaseolus vulgaris leucoagglutinin (PHA-L) was microiontophoresed into the DRN and visualized immunocytochemically; PHA-L-immunoreactive (-IR) fibers and terminals were identified in the forebrain, hypothalamus, midline and intralaminar thalamus, habenula, periaqueductal gray, locus coeruleus, parabrachial nucleus, medullary raphe and reticular nuclei, and nucleus tractus solitarius. Dual immunocytochemistry was used to identify corticotropin-releasing factor, neurotensin, and enkephalin neurons in DRN terminal fields, in some cases in close proximity to PHA-L-IR terminals. Terminal fields were identified in regions that influence nociception, and the neuroactive substances identified in these terminal fields may play modulatory roles in nociception. PMID- 8441712 TI - Should we go soft? PMID- 8441713 TI - Use of preoperatively deposited autologous blood for total knee replacement. AB - The efficacy of obviating homologous blood transfusion by an autologous blood program was investigated prospectively in a series of patients undergoing total knee replacement. Seventy-nine patients who underwent 110 consecutive total knee replacement operations (66 unilateral and 22 one-stage bilateral procedures) from 1986 to 1990 were studied. All patients who had elective procedures (86 of the 88 procedures) were encouraged to donate autologous blood prior to surgery if there were no medical contraindications. Seventy-six percent of the elective procedures (65 of 86) were done in patients who deposited autologous blood preoperatively. Homologous transfusion was required after only two of these 65 procedures (3%) in patients who predeposited autologous blood. This frequency of homologous transfusion was an order of magnitude lower than the frequency of homologous transfusion (35%) after procedures in patients who did not predeposit blood. Overall, 89% of the entire series of 88 procedures were performed in patients who received only autologous blood and 94% of the total volume of blood given after these 88 procedures was autologous. The Cell Saver was successful in salvaging an average of 287 mL of red blood cells per procedure after 36 procedures, but was not successful in saving blood after 29 others. The authors conclude that preoperatively deposited autologous blood is effective in reducing the need for homologous transfusion to patients who undergo elective total knee replacement. PMID- 8441714 TI - Fractures of the femoral shaft adjacent to long stem femoral components of total hip arthroplasty: report of seven cases. AB - Seven femoral shaft fractures adjacent to the distal aspect of long stem revision femoral components of total hip arthroplasty were evaluated at a mean of 6 years (range: 2 to 12) after fracture. Nonoperative treatment with a spica cast was used in four patients. Complications were delayed union in two patients and malunion in two. Operative treatment included revision and bone grafting in one patient and open reduction and internal fixation in two. Plate fracture and delayed union occurred in one patient. Operative treatment resulted in no malunions and earlier recovery of function than with nonoperative management. Femoral shaft fractures adjacent to long stem total hip arthroplasties are difficult to manage; the complication rate is 71%. PMID- 8441716 TI - Functional knee braces. PMID- 8441715 TI - Spinal injuries in 57 patients 17 years or younger. AB - Spinal column and cord injuries are rare in children and adolescents, and few reports in the literature that specifically address this subject. A retrospective review of medical records and radiographs of 57 patients was undertaken to identify age-related injury patterns, the incidence of neurologic deficits, and the presence of associated injuries. The most common injury in very young patients was spinal cord injury without radiographic abnormality or spinal cord injury with non-contiguous radiographic abnormality. The most common injury in older children was flexion-distraction injury, often associated with intraabdominal trauma. Adolescents tended to sustain injury patterns similar to adults. PMID- 8441717 TI - Pediatric femur fractures: an overview of treatment. AB - Femur fractures in the pediatric population are common injuries which may be either isolated or associated with polytrauma. The orthopedist is faced with treatment options ranging from skin traction to more aggressive methods, including internal or external fixation. We review the pros and cons of current treatment options. A simple treatment algorithm based on age of the patient, other associated injuries, and open vs closed injury is presented. PMID- 8441718 TI - Mechanical properties of bone after grafting with coralline hydroxyapatite: an experimental study. AB - Based on animal experiments, mechanical properties of rabbit radii after grafting artificial gaps with a coralline hydroxyapatite (CH) material are discussed. Healing velocity of complete and partial gaps after the same kind of grafting is also analyzed. Based on the results obtained from 48 gaps of 24 animals it is stated that fused grafts in both types of gaps showed bending strength of the radii similar to that of normal bone. The incidence of nonunions and infections are also discussed. It is concluded that CH is suitable in the treatment of incomplete bone defects. PMID- 8441719 TI - Interlocking intramedullary fixation of hand fractures. AB - Reduction and stabilization can be especially difficult in treating comminuted hand fractures with bone loss or nonunion. Two cases are presented to illustrate a method of intramedullary fixation using an AO mini fragment reconstruction plate, which allows interlocking fixation proximally and distally. Any defect can be filled with corticocancellous bone graft. When necessary, this graft can be fixed to the metal plate that acts as a strut. The fixation obtained is stable against rotational, angular, and compressive forces, making it a useful adjunct to the hand surgeon's armamentarium. PMID- 8441720 TI - Acute Pseudomonas infection following total hip replacement. PMID- 8441721 TI - Chronic posterolateral dislocation of the elbow in a child. PMID- 8441722 TI - Bilateral fracture dislocation of the sacrum without injury to the anterior pelvis. PMID- 8441723 TI - Osteonecrosis associated with nonunion of the hook of the hamate. PMID- 8441724 TI - Arthroscopic stabilization of anterior shoulder instability. PMID- 8441725 TI - What are the current indications for total elbow arthroplasty? Report of a case using allograft for TEA. PMID- 8441726 TI - Radiologic case study. Antibiotic modified osteomyelitis. AB - The clinical and radiologic presentation of antibiotic-modified osteomyelitis closely resembles primary subacute pyogenic osteomyelitis. The widespread use of antibiotics has increased the incidence of this entity. When a patient is found to have a solitary bone lesion, a careful history should include inquiries regarding recent antibiotic therapy for any condition. PMID- 8441727 TI - Sample size required for various methods of assessing bone status in commercial leghorn hens. AB - A study was conducted to determine the appropriate sample size required for various methods used to assess tibial bone status in commercial Leghorn hens. The methods used were in vivo bone mineral content (BMC), in vivo bone density (BD), in vitro BMC, in vitro BD, tibia bone breaking strength (TBS), and percentage bone ash (BA). Dietary total P levels of .4, .45, .5, .55, and .7% were used as treatment source of variation. Twenty hens were sampled randomly to represent each dietary treatment. The CV for each bone status comparison method was estimated and was used in a procedure to estimate the sample size requirement for detecting a difference of delta between treatments. The sample size required to detect the difference between treatment means varied depending on 1) the method used to compare bone status 2) the difference between the treatment means to be detected as significant (delta); and 3) the level of significance (alpha) assumed. The sample size required for various methods are tabulated at .01, .05, and .1 level of significance and for 2.5, 5,7.5, 10, 15, and 20% delta. To detect an actual difference of 5% from the mean to be significant, at the .05 level of significance, a sample size of 44, 22, 31, 23, 47, and 85 hens per treatment would be necessary for in vivo BMC, in vivo BD, in vitro BMC, in vitro BD, TBS, and BA methods, respectively. The estimated sample size values would help researchers in designing experiments that involve bone status comparison of commercial Leghorn hens. PMID- 8441728 TI - Early feed restriction of broilers: effects on abdominal fat pad, liver, and gizzard weights, fat deposition, and carcass composition. AB - A total of five experiments were conducted to investigate the effects of early feed restriction on organ weights, fat deposition, and carcass composition in broilers. In Experiments 1 and 2, broiler chicks were reared in litter pens for 49 days, whereas Experiments 3, 4, and 5 were conducted in battery cages for 28 days. Feed restriction in all experiments was accomplished by providing male broiler chicks 40 kcal per bird per day for 7 (Experiments 1 and 2) or 6 (Experiments 3, 4, and 5) days, starting at 4 days of age. Feed restriction of broiler pullets in Experiment 1 was imposed from 4 to 9 days of age. Furthermore, the starter and grower diets in Experiment 2 contained either 1 or 4% added fat and the starter diets in Experiments 3, 4, and 5 contained either 21 or 26% protein. No significant differences were observed for abdominal fat pad and gizzard weights, liver and carcass fat, or carcass protein between early restricted birds and ad libitum controls at 49 days of age in Experiments 1 and 2. Furthermore, with the exception of Experiment 4, no differences in abdominal fat pad weights were observed among the different feeding regimens. Significant increases in abdominal fat pad weights, percentage liver, and percentage carcass fat were noted for females at 49 days of age when compared with male broilers. Carcass fat was significantly higher and carcass protein was significantly lower in broilers fed commercial versus reduced fat diets. Broilers fed a 21% protein diet had significantly heavier abdominal fat pad weights at 28 days of age than birds fed a 26% protein diet. PMID- 8441729 TI - Influence of a novel oxy-halogen compound on early growth and nitrogen retention of broiler chickens challenged with Salmonella. AB - The potential of a novel oxy-halogen compound (OHC) to alter early growth and nitrogen retention of broiler chickens challenged with Salmonella was evaluated. Three hundred and twenty female broiler chicks (Arbor Acres x Arbor Acres) were weighed and distributed randomly within a 2 x 4 factorial arrangement of treatments. Main effects examined were the presence or absence of Salmonella typhimurium (ST) inoculation and OHC treatment. At hatching, 80 chicks were placed in electrically heated brooder batteries in each of four identical isolation rooms. Chicks designated to receive 100 microL of an oral inoculum containing 10(5) ST cfu at 3 days of age were in two of the rooms, and uninoculated chicks were raised in the other two rooms. Four replicates of 10 chicks each received drinking water containing either 0, .05, .1, or .5% OHC for each level of ST. Chicks administered .05% OHC exhibited enhanced (P < or = .01) growth at 7 and 14 days of age when compared with control values. A significant OHC by ST interaction was observed at 7 (P < or = .0001) and 14 (P < or = .03) days of age. Feed utilization was improved (P < or = .01) by OHC administration (.05 and .1%) from hatching to 7 days of age. The administration of OHC reduced (P < or = .01) nitrogen excretion and enhanced (P < or = .01) nitrogen retention by chicks at Day 7. Cecal ST log10 counts at 7 days of age for chicks given water containing 0, .05, or .1% OHC were 4.72, 3.93, and 3.74, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441730 TI - Detection of Salmonella enteritidis in experimentally infected laying hens by culturing pools of egg contents. AB - Two experiments were conducted to determine whether Salmonella enteritidis could be detected efficiently in pooled samples of the contents of eggs laid by experimentally infected hens. In Experiment 1, groups of laying hens were orally inoculated with either 10(4) or 10(6) S. enteritidis cells. In Experiment 2, one third of the hens in each group were orally inoculated with 10(6) S. enteritidis cells. At 2 wk postinoculation, culturing egg pools yielded positive results at frequencies similar to those obtained by culturing fecal samples, culturing internal organs, or testing for specific serum antibodies. Culturing fecal samples detected a higher percentage of exposed hens than egg pool culturing at 1 and 3 wk, and serum antibody tests were superior at 3 and 4 wk. In Experiment 1, more than 46% of the hens inoculated with 10(6) S. enteritidis cells laid at least one contaminated egg during the 2nd wk postinoculation. In Experiment 2, over 34% of the hens produced at least one contaminated egg during the 2nd wk postinoculation, but very few contaminated egg pools were identified during the 3rd and 4th wk. Bacteriological culturing of pooled egg contents for S. enteritidis, therefore, can apparently provide an effective method for assessing the potential public health threat posed by a flock. PMID- 8441731 TI - Influence of ambient temperature on true digestibility of protein and amino acids of rapeseed and soybean meals in broilers. AB - The effect of high ambient temperature (32 versus 21 C) between 4 and 6 wk of age on true digestibility of protein (TDP), amino acids (TDAA), and AME value of rapeseed and soybean meals was investigated in broilers. At 6 wk of age, 96 male and female birds were deprived of feed for 24 h and then force-fed with moistened diet (approximately 90 g). Excreta were collected during the two subsequent 24-h periods after force-feeding. The results of this experiment showed that the ambient temperature had no effect on AME values of the raw materials tested for both sexes of broilers. However, high ambient temperature significantly decreased (P < .001) AMEn values of the two rapeseed meals, which could be related to the nitrogen balance. Moreover, TDP and TDAA of two rapeseed and soybean meals tested in this experiment were decreased as the ambient temperature increased from 21 to 32 C. A 12% reduction in TDP value was observed with the rapeseed meals, whereas the diminution was only 5% with the soybean meal. Sex had no effect on TDP of the raw materials tested. However, for TDAA values, female birds appeared to be more sensitive to high ambient temperature than male chickens when fed rapeseed meals. PMID- 8441732 TI - Effects of dietary fat source on sudden death syndrome and cardiac sarcoplasmic reticular calcium transport in broiler chickens. AB - Wheat and soybean diets supplemented with either tallow or sunflower oil (SFO) were fed to broiler chicks. Variables examined included performance, incidence of sudden death syndrome (SDS), and cardiac sarcoplasmic reticular (SR) calcium transport. The phospholipid content of heart tissues was also determined. Birds fed the SFO diet gained significantly (P < .05) more weight over the first 21 days of age and had a significantly better feed:gain ratio (P < .01). The incidence of SDS mortality up to 39 days of age was also lower (P < .05) for SFO fed birds than for those fed the tallow diet. Calcium (45Ca2+) uptake and calcium magnesium 5'-adenosinetriphosphatase (Ca2+ + Mg(2+)-ATPase) activity in cardiac SR vesicles did not differ due to diet (P > .05). However, compared with similar weight pen-mates showing no disease signs, SDS birds had depressed 45Ca2+ uptake (P < .01) and Ca2+ + Mg(2+)-ATPase (P < .05) of cardiac SR vesicles. The phosphatidylcholine concentration in the cell membranes of heart tissue of tallow fed birds was significantly higher (P < .05) than in SFO-fed chicks. No differences were seen in other phospholipid constituents. The SDS birds, however, had significantly (P < .05) lower phosphatidylethanolamine plus phosphatidylglycerol, sphingomyelin, and total phospholipid concentrations in the heart tissues than the pen-mate controls. The results support the hypotheses that SDS in broilers is a cardiac dysfunction associated with defective cardiac SR membrane function and that dietary fat type is implicated with the syndrome. PMID- 8441733 TI - Research note: growth of Salmonella enteritidis in Grade A eggs during prolonged storage. AB - Migration of Salmonella enteritidis through egg albumen to the yolk and its subsequent growth in the yolk were examined. Submersion of eggs in .1% mercuric chloride solution for 1 h followed by submersion in 70% ethanol for 30 min resulted in an eggshell surface from which no Salmonella organisms were recovered. The eggs were then inoculated with S. enteritidis under the shell membrane. Although growth of S. enteritidis was negligible in eggs refrigerated up to 16 days, the population level of the organism increased by more than 8 log10 units in unrefrigerated eggs stored for the same amount of time. PMID- 8441734 TI - Research note: does compensatory growth occur following withdrawal of salinomycin from the diet of broilers? AB - Two floor pen studies were conducted to determine whether compensatory growth occurs following withdrawal of the anticoccidial drug salinomycin from the feed of broilers reared to 46 days of age. There were no significant differences in weight gain or feed conversion between medicated and unmedicated birds whether overall performance or performance during the 1-wk withdrawal period was measured. Feed intake of birds given salinomycin, however, was significantly lower than that of unmedicated birds, and feed intake following withdrawal was greater than that of birds still receiving the drug. PMID- 8441735 TI - Atropine and oxime treatment in lethal soman poisoning of anaesthetized guinea pigs: HLo 7 dimethanesulfonate versus HI 6 dichloride. AB - The oxime HI 6 is considered to be effective in soman poisoning and less effective in tabun poisoning. Recently, HLo 7 was shown to reactivate acetylcholinesterase (AChE) inhibited by soman and tabun. Therefore, the efficacy of HLo 7 and HI 6 was compared in soman poisoned guinea-pigs. Female Pirbright white guinea-pigs were anaesthetized with urethane (1.8 g/kg) and the a. carotis, v. jugularis and trachea were cannulated. After base line measurements soman 0.08 mg/kg (= 5 x LD50) or 0.16 mg/kg (= 10 x LD50) was injected intravenously, 2 min. later the antidotes were applied intravenously: HLo 7 0.03 or 0.1 mmol/kg, HI 6 0.03 or 0.1 mmol/kg, atropine 10 mg/kg, or a combination of atropine and an oxime. Respiratory and circulatory parameters were recorded for 60 min. or until the death of the animal. The injection of 5 x LD50 soman resulted in a rapid respiratory arrest followed by circulatory failure in the soman and soman plus oxime groups (survival time about 7 min). Atropine restored the circulatory parameters to base line but was unable to provide a sufficient respiratory function (survival time 26 min.). The combination therapy with atropine plus HLo 7 or HI 6 improved the respiration sufficiently, restored the circulation completely, and prolonged the survival time to about 50 min. Atropine treatment was insufficient in animals poisoned with 10 x LD50 soman. The combination of atropine and HLo 7 or HI 6 improved respiration, circulation, and survival time to various extent. Despite of the striking therapeutic effect no reactivation of erythrocyte AChE by the antidotes was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441736 TI - Inhibition of the vitamin B12 binding capacity of proteins by the hydrolysis product of cyclophosphamide. AB - The inhibitory effect of cyclophosphamide hydrolysis product (CPHP) on vitamin B12 binding ability to proteins has been established. The ester N-(2-chloroethyl) N'-(3-phosphopropyl)-ethylenediamine hydrochloride is probably responsible, in vitro, for blocking the protein binding sites. Preincubation of proteins with vitamin B12 prevents the inhibitory effect of CPHP. PMID- 8441737 TI - Efficacy of antidotes against soman poisoning in female physostigmine-protected rats. AB - Female rats have been found much more sensitive to lethal effects of soman than male rats. Therefore it was of interest to examine the efficacy of different antidotes against soman poisoning in females which are usually not being used in soman poisoning studies. The effects of acetylcholinesterase (AChE) non reactivating antidotes atropine and diazepam were analyzed in combination with physostigmine prophylaxis against supralethal doses of soman. Physostigmine prophylaxis was much more effective when supplemented by atropine and diazepam therapy, applied at the onset of the first signs of poisoning. The interval between the injection of a supralethal dose of soman and the appearance of signs of poisoning was shorter in physostigmine pretreated animals than in non pretreated controls poisoned with the same supralethal dose of soman. The prophylactic effect of physostigmine (used at maximal dose) disappeared in about 120 min. The addition of HI-6, an AChE-reactivating oxime, to atropine + diazepam therapy further increased the survival in soman-poisoned and physostigmine pretreated rats, yielding the highest protective ratio of 6.4. Pretreatment with physostigmine offered marked protection against inhibition of AChE by soman, as shown by enzyme activity determination in different brain regions and in diaphragm muscle. Application of HI-6 in addition to the combination of the above mentioned antidotes even preserved more AChE activity in the skeletal muscle but did not influence inhibition of the enzyme in brain. PMID- 8441738 TI - Clinical pharmacology and toxicology of cocaine. AB - Cocaine abuse has produced a major epidemic health problem in North America in the 1980s. The abuse of cocaine is maintained by the drug's effects on brain reward systems, mediated at least in part by its dopaminergic action. The patterns and consequences of use are best understood by considering the pharmacokinetics (rapid absorption and delivery to the brain, relatively short half-life) and the pharmacodynamics (intense central and peripheral neural stimulation). Cocaine is used therapeutically as a topical and local anaesthetic. Toxicity occurs primarily in cocaine abusers, but also occasionally after therapeutic dosing. Medical complications reflect primarily excessive central nervous system stimulation and excessive vasoconstriction, the latter resulting in severe hypertension and/or organ ischaemia with associated organ injury. Most deaths that result from medical complications of cocaine intoxication are sudden and occur before medical intervention is possible. Other complications of cocaine abuse with severe personal and social consequences include traumatic deaths and injuries, and reproductive disturbances, as well as transmission of infectious diseases, especially AIDS. Cocaine addiction is clearly a problem, although the number of addicts is unknown. Pharmacologic treatment of cocaine addiction has as yet been unsuccessful. Psychosocial approaches remain the mainstay of therapy. PMID- 8441739 TI - Comparison of hepatic drug-oxidizing activity after simultaneous administration of two probe drugs, caffeine and trimethadione, to human subjects. AB - Pharmacokinetic interactions between caffeine 2 mg/kg and trimethadione 4 mg/kg were evaluated in 10 healthy volunteers. Whether administered alone or together, the total body clearance (CL), the apparent volume of distribution (Vd) and half life (t1/2) of caffeine and trimethadione were the same, however, there was a weak correlation between the CL of caffeine and trimethadione [alone: r = 0.51 (P < 0.05); coadministered: r = 0.56 (P < 0.05)]. There were also weak correlations between the CL of trimethadione and the area under the serum concentration-time curves (AUC) of theobromine (r = -0.61, P < 0.05), paraxanthine (r = -0.69, P < 0.05) and theophylline (r = -0.60, P < 0.05), when the two drugs were administered alone. After combined administration, the correlation between the CL of trimethadione and the AUCs of the metabolites of caffeine were as follows: theobromine r = -0.63 (P < 0.05); paraxanthine r = -0.68 (P < 0.05); theophylline r = -0.65 (P < 0.05). These findings suggest that caffeine and trimethadione metabolism in healthy subjects is mediated by only in part by a form(s) of P450 enzymes involved. PMID- 8441740 TI - Effects of six months' white spirit inhalation exposure in adult and old rats. AB - In two separate experiments in rats the irreversible effects of six months' exposure to white spirit (0, 400 p.p.m., and 800 p.p.m.) were studied. In one experiment the exposure started at the age of three months, in the other the rats were 15 months at the beginning of the exposure. After an exposure-free period of several months neurobehavioural, pathological, and neurochemical examinations were performed. A marked difference in motor activity between young and aged animals was found. A slight effect on kidney function was seen at 800 p.p.m. No macroscopic or histopathological changes related to dosing were found. The concentrations of noradrenaline, dopamine, and 5-hydroxytryptamine in various brain regions and in whole brain were irreversibly changed. In conclusion, the study revealed different changes within the CNS, but failed to demonstrate neurobehavioural white spirit-induced neurotoxicity. PMID- 8441741 TI - Cardiotoxic effects of nitrofurantoin and tertiary butylhydroperoxide in vitro: are oxygen radicals involved? AB - Langendorff rat hearts were perfused for 15, 30 or 75 min. with the oxygen radical generators nitrofurantoin (0.25 or 0.5 mmol/l) or tertiary butylhydroperoxide (0.25 mmol/l). Both agents reduced the force of contraction and increased the release of glutathione, oxidized glutathione, lactate dehydrogenase and creatine phosphokinase into the perfusion fluid. The tissue concentration of glutathione was reduced. While there were no signs of an increased production of conjugated dienes, the tissue concentration of malondialdehyde was greater than in control experiments. The variability of the latter effect was large, however, and in most cases the increase was not statistically significant. Addition of catalase (100 mU/ml) or catechin (0.5 mmol/l) to the perfusion medium abolished the nitrofurantoin induced release of oxidized glutathione but did not not prevent or attenuate enzyme leakage from the cells and the development of a negative inotropic effect. These results suggest that the cardiotoxic effects of nitrofurantoin and tertiary butylhydroperoxide cannot be explained by the appearance of oxygen radicals alone and that an increased lipid peroxidation is not the mechanism which is primarily responsible for cell death. PMID- 8441742 TI - Oesophageal and gastric potential difference and pH in healthy volunteers following intake of coca-cola, red wine, and alcohol. AB - Alcohol causes gastroesophageal reflux and mucosal damage in the oesophagus and the stomach. The transmucosal electrical potential difference gives information on gastric mucosal integrity and function, while the validity of oesophageal measurements have been discussed. Baseline oesophageal potential difference measurements were performed three times with an interval of at least one week. We found oesophageal potential difference measurements reliable with an acceptable reproducibility. Oesophageal and gastric potential difference and pH were measured by use of a new microelectrode principle in 10 healthy volunteers following intake of coca-cola, wine and alcohol. Oesophageal and gastric potential difference decreased after intake of 250 ml coca-cola, 250 ml 11 vol% red wine and 60 ml 43 vol% whisky. Gastric potential difference decreased after intake of 250 ml ethanol 11 vol% and 60 ml ethanol 43 vol%. Intake of red wine and whisky resulted in a significant greater gastric potential difference decrease compared to similar concentrations and volumes of ethanol. The time until the potential difference had regained baseline level was longer after intake of red wine compared to coca-cola, whisky and ethanol. Oesophageal pH decreased after intake of coca-cola and red wine, but was unchanged after whisky. Gastric pH was unchanged after intake of all the drinks. In conclusion, the gastric potential difference reduction was not correlated to alcohol concentration. Red wine seems to affect the gastric potential difference more than coca-cola, whisky and ethanol. The observed changes in oesophageal and gastric potential difference might be due to changes in Cl- secretion and/or due to a damaging effect of the additives of the beverages. PMID- 8441743 TI - Differences in performance in three strains of rats in a 5-choice serial reaction time task. AB - Possible discrepancies between an albino stock (Wistar), a mixed strain (pigmented/albino, Brown Norwegian x Lewis) and a pigmented strain (Long Evans) of rats in the acquisition and performance of a visual task for attention were investigated. It was expected that Wistar rats were less accurate in performance of the task, considering the visual deficits genetically linked to albinism in rodents. However, Wistar performed with the same accuracy, speed and impulsivity as Long Evans. The Brown Norwegian/Lewis rats had a decreased responding, speed and impulsivity. During task acquisition they responded with the same accuracy as the other two types of rats. After task acquisition they were also less accurate. IN CONCLUSION: It seems reasonable to use Wistar rats as well as Long Evans for the present task. PMID- 8441744 TI - Effect of nitrous oxide on haematopoiesis in vitro: biochemical and functional features. AB - Prolonged exposure to nitrous oxide (N2O) can induce dyshaematopoiesis by causing a functional cobalamin-deficiency state through oxidation of methyl-cobalamin (vitamin B12). Herein, we demonstrate that N2O exposure of murine bone marrow cells in vitro results in both functional and biochemical perturbations. In haematopoietic and bone marrow stromal cells, N2O exposure results in a decrease in methionine synthetase activity with a corresponding increase in homocysteine efflux. In semisolid cultures, N2O inhibits colony formation by cells belonging to the colony forming unit in culture (CFU-C) compartment. In contrast, N2O exposed stromal cell layers maintain the ability to bind and support the differentiation of haematopoietic progenitor cells upon reseeding. Together, these data suggest that the dyshaematopoiesis seen after exposure to N2O is mediated through a direct inhibitory effect on haematopoietic cells. PMID- 8441745 TI - [The ethical status of the child in family and child psychotherapy]. AB - The implications of the United Nations' Convention on the Rights of the Child for psychotherapy and family therapy with the children are elaborated. Referring to the ethical discourse about patient information and informed consent, the authors suggest to integrate minors into decisions about participation in and goals of therapy. Shortcomings of common ways in dealing with minors in therapy are analyzed and discussed in the light of ethical principles. Empirical data concerning adequate judgments about competences of children are evaluated and suggestions for practical work in therapy and counseling are presented. PMID- 8441746 TI - [Sleep disorders in early childhood: developmental psychopathologic model and pilot study]. AB - Sleep disorders are early childhood problems with a relatively high prevalence and persistence. An integrative concept is presented which conceptualizes sleep disorders as a result of early self-regulation problems in the infants and various but unsuccessful soothing strategies, parental depressive mood, loss of feelings of self-efficacy and control. Experiences in behavioral therapy underline the importance of parental cognitive processes in coping with night waking. Data from a pilot-study are presented which included 20 infants (7-24 months). Questionnaires show that the infants are perceived as more difficult, their mothers feel more stressed and depressed, less in control of the problem than a control group. Night-waking has a strong emotional negative valence. Implications for counseling are discussed. PMID- 8441747 TI - [Effectiveness of the Gordon parent training]. AB - The analysis of recent reviews concerned with the efficacy of Parent Effectiveness Training (PET) demonstrates, within limits, its reliability and helpfulness as a therapeutic measure for children and adolescents. However, parents do seem to benefit more than their offsprings, on whom, judged by outcome, the effectiveness seems minor. As to its indication, open questions remain. Taking everything into account it would seem somewhat unjust or premature, to erasure PET from the catalogue of approved measures. PMID- 8441748 TI - [The importance of school achievements in adolescents with anorectic disorders]. AB - The question of pathologic roots of achievement patterns in girls and boys suffering from anorectic disorders is investigated by empirical and theoretical means. Records of 59 inpatients were reviewed with special emphasis on premorbid school achievement and its development during therapy. 44 completed a catamnestic questionnaire or interview. 10 students performed better, 10 worse. The latter differed in severity of clinical symptoms, duration of stay and continuing therapy, improvement in aggressiveness, recurring menstruation and changes in family interactions. Results are discussed regarding psychodynamic issues. PMID- 8441749 TI - Structural energetics of peptide recognition: angiotensin II/antibody binding. AB - The ability to predict the strength of the association of peptide hormones or other ligands with their protein receptors is of fundamental importance in the fields of protein engineering and rational drug design. To form a tight complex between a flexible peptide hormone and its receptor, the largeloss of configurational entropy must be overcome. Recently, the crystallographic structure of the complex between angiotensin II and the Fab fragment of a high affinity monoclonal antibody has been determined (Garcia, K.C., Ronco, P.M., Verroust, P.J., Brunger, A.T., Amzel, L.M. Three-dimensional structure of an angiotensin II-Fab complex at 3 A: Hormone recognition by an anti-idiotypic antibody. Science 257:502-507, 1992). In this paper we present a study of the thermodynamics of the association by high sensitivity isothermal titration calorimetry. The results of the experiments indicate that at 30 degrees C the binding is characterized by (1) a delta H of -8.9 +/- 0.7 kcal mol-1, (2) a delta Cp of -240 +/- 20 cal K-1 mol-1, and (3) the release of 1.1 +/- 0.1 protons per binding site in the pH range 6.0-7.3. Using these values and the previously determined binding constant in phosphate buffer, delta G at 30 degrees C is estimated as -11 kcal mol-1 and delta S as 6.9 cal K-1 mol-1. The calorimetric data indicate that binding is favored both enthalpically and entropically. These results have been complemented by structural thermodynamic calculations. The calculated and experimentally determined thermodynamic quantities are in good agreement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441750 TI - Successful prediction of the coiled coil geometry of the GCN4 leucine zipper domain by simulated annealing: comparison to the X-ray structure. AB - The recently solved X-ray structure of the dimerization region ("leucine zipper") of the yeast transcriptional activator GCN4 (O'Shea, E.K., Klemm, J.D., Kim, P.S., Alber, T. Science 254:539-544, 1991) is compared to previously predicted models which had been obtained by a conformational search procedure employing simulated annealing without any knowledge of the crystal coordinates (Nilges, M., Brunger, A.T. Protein Eng. 4:649-659, 1991). During the course of the simulated annealing procedure, the models converged towards the X-ray structure. The averaged root mean square difference between the models and the X-ray structure is 1.26 and 1.75 A for backbone atoms and all nonhydrogen atoms at the dimerization interface, respectively. The local helix-helix crossing angle of the X-ray structure falls within the range predicted by the models; a slight unwinding of the coiled coil toward the N-terminal DNA-binding end of the dimerization region has been correctly predicted. Distance maps between the helices are largely identical. The region around asparagine 20 is asymmetric in the X-structure and in the models. Surface side chain dihedrals showed a large variation in the models although the chi 1, chi 2, chi 3, chi 4 3-fold dihedrals were correctly predicted in 69, 42, 43, and 44% of the cases, respectively. Phenomenological free energies of dimerization of the models show little correlation with the root mean square difference between the models and the X-ray structure. PMID- 8441751 TI - Crystal structure of CTP-ligated T state aspartate transcarbamoylase at 2.5 A resolution: implications for ATCase mutants and the mechanism of negative cooperativity. AB - The X-ray crystal structure of CTP-ligated T state aspartate transcarbamoylase has been refined to an R factor of 0.182 at 2.5 A resolution using the computer program X-PLOR. The structure contains 81 sites for solvent and has rms deviations from ideality in bond lengths and bond angles of 0.018 A and 3.722 degrees, respectively. The cytosine base of CTP interacts with the main chain carbonyl oxygens of rTyr-89 and rIle-12, the main chain NH of rIle-12, and the amino group of rLys-60. The ribose hydroxyls form polar contacts with the amino group of rLys-60, a carboxylate oxygen of rAsp-19, and the main chain carbonyl oxygen of rVal-9. The phosphate oxygens of CTP interact with the amino group of rLys-94, the hydroxyl of rThr-82, and an imidazole nitrogen of rHis-20. Recent mutagenesis experiments evaluated in parallel with the structure reported here indicate that alterations in the hydrogen bonding environment of the side chain of rAsn-111 may be responsible for the homotropic behavior of the pAR5 mutant of ATCase. The location of the first seven residues of the regulatory chain has been identified for the first time in a refined ATCase crystal structure, and the proximity of this portion of the regulatory chain to the allosteric site suggests a potential role for these residues in nucleotide binding to the enzyme. Finally, a series of amino acid side chain rearrangements leading from the R1 CTP allosteric to the R6 CTP allosteric site has been identified which may constitute the molecular mechanism of distinct CTP binding sites on ATCase. PMID- 8441752 TI - Metal poison inhibition of carbonic anhydrase. AB - Carbonic anhydrase is inhibited by the "metal poison" cyanide. Several spectroscopic investigations of carbonic anhydrase where the natural zinc ion has been replaced by cobalt have further strengthened the view that cyanide and cyanate bind directly to the metal. We have determined the structure of human carbonic anhydrase II inhibited by cyanide and cyanate, respectively, by X-ray crystallography. It is shown that the inhibitors replace a molecule of water, which forms a hydrogen bond to the peptide nitrogen of Thr-199 in the native structure. The coordination of the zinc ion is hereby left unaltered compared to the native crystal structure, so that the zinc coordinates three histidines and one molecule of water or hydroxyl ion in a tetrahedral fashion. The binding site of the two inhibitors is identical to what earlier has been suggested to be the position of the substrate (CO2) when attacked by the zinc bound hydroxyl ion. The peptide chain undergoes no significant alterations upon binding of either inhibitor. PMID- 8441753 TI - A novel parameterization scheme for energy equations and its use to calculate the structure of protein molecules. AB - A novel scheme for the parameterization of a type of "potential energy" function for protein molecules is introduced. The function is parameterized based on the known conformations of previously determined protein structures and their sequence similarity to a molecule whose conformation is to be calculated. Once parameterized, minima of the potential energy function can be located using a version of simulated annealing which has been previously shown to locate global and near-global minima with the given functional form. As a test problem, the potential was parameterized based on the known structures of the rubredoxins from Desulfovibrio vulgaris, Desulfovibrio desulfuricans, and Clostridium pasteurianum, which vary from 45 to 54 amino acids in length, and the sequence alignments of these molecules with the rubredoxin sequence from Desulfovibrio gigas. Since the Desulfovibrio gigas rubredeoxin conformation has also been determined, it is possible to check the accuracy of the results. Ten simulated annealing runs from random starting conformations were performed. Seven of the 10 resultant conformations have an all-C alpha rms deviation from the crystallographically determined conformation of less than 1.7 A. For five of the structures, the rms deviation is less than 0.8 A. Four of the structures have conformations which are virtually identical to each other except for the position of the carboxy-terminal residue. This is also the conformation which is achieved if the determined crystal structure is minimized with the same potential. The all C alpha rms difference between the crystal and minimized crystal structures is 0.6 A.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441754 TI - A geometrical constraint approach for reproducing the native backbone conformation of a protein. AB - It is known that the backbone conformation of a protein can be reproduced with precision once a correct contact map (two-dimensional representation showing residue pairs in contact) is given as geometrical constraints. There is, however, no way to infer the correct contact map for a protein of unknown structure. We started with one-dimensional constraints using the quantity N14 (the number of neighboring residues within the radius of 14 A). Since the plot of N14 along a chain shows a good correlation with the corresponding amino acid sequence, the N14 profile obtained from the X-ray structure is predictable from the sequence. Construction of backbone conformations under a given N14 profile was carried out in the following two steps: (1) a contact map from the N14 profile was produced by taking the product of N14 values of every two residues; (2) backbone conformations were generated by applying the distance geometry technique to distance constraints given by the contact map. If present, disulfide bonds in a protein, as well as the secondary structure, were treated as additional constraints, and both cases with or without the additional information were examined. The method was tested for 11 proteins of known structure, and the results indicated that the reproduced conformation was fairly good, using an X ray structure for comparison, for small proteins of less than 80 residues long. The basic assumption and effectiveness of the present method were compared with those of previous studies employing the geometrical constraint approach.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441755 TI - Purification, crystallization, and preliminary X-ray studies on the rhizome lectin from stinging nettle and its complex with NN'N"-triacetylchitotriose. AB - Single crystals were grown from affinity-purified stinging nettle lectin and from its complex with the specific trisaccharide NN'N"-triacetylchitotriose by vapor diffusion at room temperature. The lectin crystallizes in space group P2(1)2(1)2(1) with unit cell dimensions a = 54.3 (1) A, b = 62.2 (1) A, and c = 92.4 (2) A, and diffracts to 3.0 A resolution. The asymmetric unit contains three lectin monomers. The crystals of the lectin-trisaccharide complex have space group P2(1)2(1)2(1) with cell constants a = 37.69 (4) A, b = 48.97 (6) A, and c = 57.32 (4) A. These crystals diffract to at least 2.0 A resolution and the asymmetric unit contains one lectin monomer. A three-dimensional X-ray structure determination is on its way. PMID- 8441756 TI - Crystallization and preliminary X-ray crystallographic analysis of arylesterase from Pseudomonas fluorescens. AB - Large crystals of arylesterase from Pseudomonas fluorescens have been grown at room temperature using ammonium sulfate as a precipitant. They grow to dimensions of 0.7 x 0.7 x 0.6 mm3 within a month. The crystals belong to the trigonal space group P3(1) (or P3(2)), with unit cell dimensions of a = 147.12 A and c = 131.08 A. The asymmetric unit seems to contain six molecules of dimeric arylesterase, with corresponding crystal volume per protein mass (VM) of 2.53 A3/Da and solvent fraction of 51.5% by volume. The crystals diffract to at least 2.2 A Bragg spacing when exposed to X-rays from a rotating-anode source. X-ray data have been collected to 2.9 A Bragg spacing from native crystals. PMID- 8441757 TI - Cysteine and glutathione deficiency in AIDS patients: a rationale for the treatment with N-acetyl-cysteine. AB - A series of clinical studies and laboratory investigations suggests that the acquired immunodeficiency syndrome (AIDS) may be the consequence of a virus induced cysteine deficiency. HIV-infected persons at all stages of the disease were found to have decreased plasma cystine and cysteine concentrations and decreased intracellular glutathione levels. In rhesus macaques, cysteine levels decrease already within 1-2 weeks after infection with the closely related virus SIVmac. HIV-infected persons and SIV-infected rhesus macaques have also, on the average, substantially increased plasma glutamate levels. Increased glutamate levels aggravate the cysteine deficiency by inhibiting the membrane transport of cystine. Even moderately elevated extracellular glutamate levels as they occur in HIV-infected persons cause a substantial decrease of intracellular cysteine levels. Clinical studies revealed that individual cystine and glutamate levels are correlated with the individual lymphocyte reactivity and T4+ cell counts but not T8+ cell counts. This phenomenon was demonstrated not only in HIV-infected persons but also in healthy human individuals. The cellular cysteine supply affects amongst others the intracellular glutathione level and IL-2-dependent proliferation of T cells and (inversely) also the activation of the transcription factor NF-kappa B. The cysteine deficiency of HIV-infected persons is, therefore, possibly responsible not only for the cellular dysfunction but also for the overexpression of tumor necrosis factor-alpha (TNF-alpha), interleukin-2 receptor alpha-chain, and and beta 2-microglobulin. All the corresponding genes are associated with kappa-like enhancer sequences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441758 TI - Effects of naltrexone on pharmacodynamics and pharmacokinetics of intravenously administered morphine in the rat. AB - Effects of naltrexone administered intravenously on the pharmacological actions and kinetics of morphine in serum following intravenous administration of morphine were determined in male Sprague-Dawley rats. A 10 mg/kg dose of morphine produced an analgesic response as measured by the tail flick test. Morphine also produced a hyperthermic effect. Naltrexone dose (0.625-2.5 mg/kg)-dependently antagonized the analgesic and hyperthermic effects of morphine. The effect of naltrexone (0.625 and 2.5 mg/kg) on the pharmacokinetic parameters area under the serum morphine concentration time curve (AUC0-->infinity), serum levels of morphine extrapolated to zero time (Cmax), half-life (t1/2), mean residence time (MRT), total body clearance (Clt), and volume of distribution at steady state (Vss) of morphine in serum was determined. Naltrexone (0.625 mg/kg) significantly increased AUC0-->infinity, Cmax, t1/2 MRT, but decreased the Vss, elimination rate constant (k) and Clt. The higher dose of naltrexone (2.5 mg/kg) produced an increase in the Cmax value of morphine in the serum, but the other pharmacokinetic parameters were unaffected. Since increased morphine concentrations in serum produced by naltrexone cannot explain its antagonistic effects on analgesia and hyperthermia, it is concluded that naltrexone produces its effects by blocking opiate receptors at the appropriate sites. The increases in serum morphine levels by naltrexone may be related to displacement of morphine from protein binding sites and inhibition of morphine metabolism by glucuronyl transferase. This study for the first time demonstrates that in the rat, when morphine and naltrexone are given concurrently, although serum levels of morphine increase, pharmacological effects of morphine are antagonized.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441760 TI - N-acetylcysteine: potential for AIDS therapy. AB - The observations that people infected with HIV suffer not only from an inflammatory stress but also from depleted glutathione levels have led to a general hypothesis that these two are causally related, and that treatment of AIDS should include thiol-replenishment therapy. In particular, inflammatory stimulations are dependent on intracellular thiol levels, as they are potentiated at low glutathione levels (oxidative stress) and inhibited at high glutathione levels. Inflammatory stress may itself lead to decreased levels of glutathione. HIV has taken advantage of inflammatory signals to regulate its own replication; thus, the HIV infection is exacerbated by low levels of glutathione. We have shown that N-acetylcysteine can inhibit inflammatory stimulations, including that of HIV replication. Since N-acetylcysteine can replenish depleted glutathione levels in vivo, we suggest that it be used as an adjunct in the treatment of AIDS. PMID- 8441759 TI - Structure-activity relationships for 2-substituted adenosines at A1 and A2 adenosine receptors. AB - A series of 55 2-alkyloxy-, 2-aryloxy- and 2-aralkyloxy-adenosines was screened as inhibitors of the binding of [3H]R-phenyl-isopropyladenosine to A1 adenosine receptors in rat cerebral cortical membranes, and of the binding of [3]N ethylcarboxamidoadenosine to A2 adenosine receptors in rat striatal membranes and as agonists at A2 adenosine receptors coupled to adenylate cyclase in rat pheochromocytoma PC12 cell membranes. The activities are consonant with a hydrophobic binding site in the A2 receptors at a distance from the 2-position of the adenine ring corresponding to a spacer chain of -O-CH2-CH2-. These is little lateral steric tolerance in the region occupied by the spacer chain. Interaction with the hydrophobic binding site is greatest in the 2-alkyloxy series for 2 cyclohexylethoxy-, 2-cyclohexylpropoxy- and 2-cyclohexylbutoxyadenosines and in the 2-aralkoxy series for 2-phenylethoxy-, 2-(4-methylphenyl)ethoxy-, 2-(4 chlorophenyl)ethoxy-, and 2-naphthylethoxy-adenosine. The affinities of the 2 substituted adenosines for the rat cerebral cortical A1 receptors are not as markedly altered by structural changes and are in almost all cases two- to hundredfold less than the affinity of the 2-substituted adenosine for the rat striatal A2 receptor. There is excellent correspondence of the present data on rat A2 receptors with reported potencies of these 2-substituted adenosines as coronary vasodilators in guinea pig heart preparations. PMID- 8441761 TI - Effect of cilazapril on exercise tolerance in congestive heart failure. AB - Cilazapril (C), an angiotensin-converting enzyme inhibitor with effective antihypertensive efficacy, was examined for its ability to alter exercise tolerance testing (ETT) and respiratory oxygen uptake in 33 patients with congestive heart failure (CHF). C was administered in capsules daily to patients with New York Heart Association Class II or Class III CHF for 12 weeks, in parallel double-blind treatment groups of 0 mg (n = 8), 0.5 mg (n = 8), 1.0 mg (n = 9), and 2.5 mg (n = 8). The blood pressure (BP) was reduced by 2.5 mg C: systolic BP (SBP) from 126 to 114 mm Hg; diastolic BP from 76 to 69 mm Hg. The maximum heart rate (MHR) during ETT was increased by 2.5 mg C from 137 to 143 bpm, as was the double product (MHR x maximum SBP x 0.01) from 237 to 251. There was an insignificant change in duration of exercise (548-610 s), anaerobic threshold (AT), and maximum oxygen uptake (14.1-15.7 ml/kg/min). The results suggest a positive effect of 2.5 mg C on energy utilization in CHF patients. PMID- 8441762 TI - Islet lysosomal enzyme activities and glucose-induced insulin secretion: effects of mannoheptulose, 2-deoxyglucose and clonidine. AB - In previous investigations we have shown a striking relationship between the activity of glycogenolytic glucose producing acid hydrolases in pancreatic islet tissue and certain insulin-releasing processes. In the present investigation we have studied the relation between islet lysosomal enzyme activities and glucose induced insulin secretion in vitro in the presence of various insulin secretory inhibitors. It was observed that the nonmetabolizable glucose analogue, mannoheptulose (5 mmol/l) did induce a 2-fold increase in insulin release at low (1 mmol/l) glucose, and a total suppression of insulin release at high (16.7 mmol/l) glucose. These changes in the insulin-secretory pattern were accompanied by similar changes in the activity of islet acid alpha-glucosidase. The activities of neutral alpha-glucosidase (endoplasmic reticulum) or acid phosphatase and N-acetyl-beta-D-glucosaminidase (lysosomes) were not affected by mannoheptulose. 2-Deoxyglucose (5 mmol/l), another glucose analogue, did not increase insulin secretion or acid alpha-glucosidase activity at low glucose. At high glucose, however, a partial inhibition of both insulin release (approximately 50%) and acid alpha-glucosidase activity was seen. 2-Deoxyglucose slightly suppressed acid phosphatase activity but did not influence the activities of neutral alpha-glucosidase or N-acetyl-beta-D- glucosaminidase. Direct addition of glucose to islet homogenates showed a suppressive effect on alpha-glucosidase activity at pH 4.0 and 5.0. The glucose analogues displayed only marginal (-10%) inhibition of alpha-glucosidase activity at pH 5.0. No effect of the analogues was seen at pH 4.0.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441763 TI - Cocaine and body temperature: effect of exercise at high ambient temperature. AB - The laboratory rat has been used as an animal model to investigate the effects of cocaine on body temperature and to determine if abuse of the drug is a risk factor in the pathogenesis of exercise-induced heat stroke. Animals were trained to run on a treadmill which was enclosed so that the ambient temperature could be regulated. Exercise at ambient temperatures of 20 and 30 degrees C led to a similar rise in core temperature of approximately 1 degrees C, although the starting core temperature was higher in the rats at 30 degrees C (38.5 +/- 0.10 degrees C compared to 37.9 +/- 0.06 degrees C). Cocaine (20 mg/kg) led to a transient fall in core temperature in the 20 degrees C group; the temperature then rapidly recovered, so that after 60 min exercise there was no significant difference between these and the control animals. At the higher ambient temperature cocaine augmented the rise in core temperature during running, although the animals had regained thermal balance by 30 min and core temperature was maintained at 40.2 +/- 0.13 degrees C until the end of the exercise period. The dopamine D1 receptor antagonist SCH 23390 (0.1, 0.3 or 1.0 mg/kg) led to suppression of spontaneous motor activity so that the rats could be persuaded to exercise for only 30-45 min after treatment. Pretreatment with the antagonist did not affect the rise in core temperature induced by cocaine at 30 degrees C which again stabilized by 30 min at 40.0 +/- 0.12 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441764 TI - Demonstration of antidiarrheal and antimotility effects of wood creosote. AB - Wood creosote administered to rats prevented castor-oil-induced diarrhea with an ED50 of 53 mg/kg p.o. This antidiarrheal effect was apparently produced by acceleration of net fluid absorption from the intestine, as shown by a 52% decrease (p < 0.001) of residual fluid volume in an intestinal loop, and partly by suppression of intestinal motility. Wood creosote also inhibited spontaneous longitudinal contractions of isolated ileal segments in rats (IC50 = 28 mg/l) and guinea pigs (IC50 = 17 mg/l). Contractions of the guinea pig ileum induced by electrical stimulation, bradykinin and acetylcholine were also inhibited dose dependently. We conclude that wood creosote has an antidiarrheal activity and that this effect is exerted by inhibition of intestinal motility and by augmentation of net fluid absorption from the intestine. PMID- 8441765 TI - An ultraviolet-sensitive mutant of Zymomonas mobilis affecting the stability of its natural plasmid pZMO2. AB - Plasmid pZMO2, a 1.9-kb natural plasmid of Zymomonas mobilis strain ATCC 10988, was found to be absent from the extract of a mutant isolate sensitive to ultraviolet irradiation, methyl methanesulfonic acid, and mitomycin C. This mutant, named uvs51, also exhibited extremely high segregational instability of the recombinant plasmid pDS212, whose maintenance in the parental strain is known to be due to pZMO2 sequences. Helped conjugations, employing uvs51 as recipient with Escherichia coli donors containing the conjugative plasmid pRK2013 and a mobilizable recombinant plasmid carrying the Rhizobium meliloti recA gene, showed complementation of uvs51 with the recA functions. Moreover, uvs51/recA stable transconjugants, containing the recA sequence integrated into their chromosomes, showed an increased stability of recombinant plasmid pDS212. The data presented here indicate that the stable maintenance of the natural plasmid pZMO2 in Z. mobilis is affected by a putative recA function. PMID- 8441766 TI - Isolation and characterization of a linear plasmid from the entomopathogenic fungus Ascosphaera apis. AB - An extrachromosomal DNA plasmid was isolated from both mating types of the entomopathogenic fungus Ascosphaera apis and named pAaL. The subculture in which pAaL was first identified originated from mummified honey bee larvae from an apiary in Wyoming. Very similar, homologous plasmids were found in 9 out of 10 of isolates collected from diverse geographic locations. The plasmid is found inside the mitochondria, has the same buoyant density as mitochondrial DNA in bisbenzamide--CsCl gradients, and does not contain sequences homologous to either mitochondrial DNA or genomic DNA. The plasmid is linear, double-stranded, of 12 kilobase pair, and has a higher copy number than the mitochondrial DNA. Endonuclease and exonuclease digestions suggest that an inverted repeat is probably present at each terminus and that pAaL has two blocked 5' ends, probably due to the presence of terminal binding proteins. Restriction site data showed pAaL to be AT-rich. There were no apparent differences in the growth rate, culture appearance, and reproductive cycle of plasmid-bearing or plasmid-free A. apis isolates. pAaL was stably inherited in the plasmid-free strains, but it was lost in the progeny of crosses and reciprocal crosses between the plasmid-free strain and plasmid-bearing strains. The biological function of this plasmid has not yet been determined. PMID- 8441767 TI - Lack of substantial sequence homology between the cryptic plasmid and chromosome of Neisseria gonorrhoeae. AB - Previous reports have suggested that either large segments of the 4.2-kb phenotypically cryptic plasmid or the entire plasmid are integrated into the chromosome of Neisseria gonorrhoeae, even in rare plasmid-free strains. A series of subclones of the cryptic plasmid have been used in Southern blotting experiments to map the extent of this hybridization with the chromosome. Hybridization could only be detected at low or medium stringency, and the data suggest the absence of entire plasmids, or even large contiguous sections of the cryptic plasmid, in the chromosome of N. gonorrhoeae. In confirmation of this, a chromosomal fragment that hybridizes to the cryptic plasmid was cloned and sequenced. The low stringency hybridization between the cryptic plasmid and chromosome seems to be the result of short repetitive sequences found in both DNA molecules, rather than full or partial plasmid integration. PMID- 8441768 TI - Biochemical and genetic analysis of the unidirectional theta replication of the S. agalactiae plasmid pIP501. AB - pIP501 is a broad-host-range plasmid originating from Streptococcus agalactiae. In this report we show that (i) it replicates by a theta mechanism initiating at the 3' end of the gene encoding the replication protein RepR and progressing in the direction of transcription of this gene; (ii) its replication origin lies within or a few nucleotides downstream from ORF R and not upstream from it as suggested in the literature (Brantl et al. (1990) Nucleic Acids Res. 18, 4783 4789); (iii) the RepR protein positively regulates pIP501 copy number; and (vi) the main function ensured by the sequences located upstream from ORF R is to express this ORF. Since the replication properties of pIP501 are indistinguishable from those of the highly related Enterococcus faecalis plasmid pAM beta 1, we conclude that these elements form the first family of theta replicating plasmids in gram-positive bacteria. Based on sequence similarities, we extend this family to the S. pyogenes plasmid pSM19035 and to 12 other plasmids isolated from streptococci or enterococci. PMID- 8441769 TI - Identification of the minimal replicon of the streptomycete plasmid pIJ101. AB - The minimal replicon of pIJ101 was defined to a 2.0-kb BalI-SacII fragment containing the rep ORF and a non-coding region of DNA, but not orf56 (pQR435). This non-coding region of DNA was found to be crucial for plasmid replication in Streptomyces lividans and may contain either the origin of replication or the rep promoter (or both). A 1.4-kb NotI-SacII fragment containing only the rep ORF produced a 54-kDa protein in vitro when expressed from the lacZ promoter. pQR435 was structurally unstable in S. lividans and accumulated single-stranded (ss)DNA. The insertion of the site for second-strand initiation (ssi) into pQR435 did not prevent the plasmid from rearranging or from accumulating ssDNA. PMID- 8441770 TI - The complete nucleotide sequence of a small cryptic plasmid from a rumen bacterium of the genus Butyrivibrio. AB - The complete nucleotide sequence of a plasmid, designated pRJF1, isolated from a rumen bacterium of the genus Butyrivibrio, has been determined. pRJF1 is a small plasmid (2631 bp) which shows the high AT content (64%) typical of plasmids from gram-positive organisms. Computer analysis of sequence data revealed two major open reading frames encoded on the same strand but in different frames. The smaller, ORF1 (435 bp), is preceded by Shine Dalgarno (SD) and Escherichia coli 10, -35 sequences and is predicted to encode an acidic polypeptide of 145 aa. The putative protein shows little homology to known bacterial proteins except in a small region similar to part of the Pre protein (plasmid recombination enzyme) of Bacillus plasmid pTB913. Pre proteins of the pTB913 family, however, show conservation of several amino acids in the amino terminal region of the protein that may be related to function. This pattern of amino acid conservation is not observed in ORF1. The predicted product of ORF2 (849 bp) is a basic protein of 283 as that shows significant similarity to repA gene products of plasmids from gram-negative (but not gram-positive) bacteria. No typical Shine Dalgarno sequence or -10, -35 sequences precede this coding region. While sequence homologous to nick sites of plasmids from gram-positive organisms that replicate via ssDNA intermediates were also detected in pRJF1, the order of the three consecutive inverted repeats typical of nick sites is not conserved. pRJF1, however, does contain an extended region of directly and inversely repeated sequence motifs reminiscent of theta replication origins. PMID- 8441771 TI - Stability analysis of the Lactococcus lactis DRC1 lactose plasmid using pulsed field gel electrophoresis. AB - Pulsed-field agarose gel electrophoresis of SmaI digests of genomic DNA was used to examine lactose plasmid copy number and stability in Lactococcus lactis. In L. lactis strain DRC1, the plasmid was found to exist as a single-copy plasmid. Transconjugants of strain HID113 carrying this plasmid were unstable. Variants were isolated with improved phenotypic stability resulting from improved maintenance of the lactose plasmid or from integration of part of the plasmid into the lactococcal chromosome. PMID- 8441772 TI - Nocardioform arsenic resistance plasmid characterization and improved Rhodococcus cloning vectors. AB - A representative of a group of related Rhodococcus arsenic resistance plasmids was characterized, locating the resistance genes and regions influencing host range and controlling copy number. This information, together with identification of antibiotic resistance determinants to replace the arsenic marker was used to construct Rhodococcus-Escherichia coli positive selection shuttle plasmids which, compared with those previously constructed, had half the size, a much higher copy number, and chloramphenicol rather than arsenic as selectable marker. PMID- 8441773 TI - Anti-inflammatory activity of resins from some species of the plant family Burseraceae. AB - The anti-inflammatory activities of extracts from the resins of four species of the plant family Burseraceae, Boswellia dalzielli, Boswellia carteri (gum olibanum), Commiphora mukul, and Commiphora incisa, were studied. The aqueous extracts of the resins of B. dalzielli, C. incisa, and C. mukul significantly inhibited both the maximal edema response and the total edema response during 6 h of carrageenan-induced rat paw edema. The octanordammarane triterpenes, mansumbinone and mansumbinoic acid, isolated from the resin of C. incisa, were separated and tested. Administered prophylactically, mansumbinone proved to be more than 20 times less potent than indomethacin and prednisolone in inhibiting carrageenan-induced rat paw edema. However, the molar potency of mansumbinoic acid was within one order of magnitude of those of indomethacin and prednisolone. The anti-inflammatory action of the acid on the carrageenan-induced edema was dose-related between 1.3 x 10(-5) and 2.5 x 10(-4) mol kg-1 when given before the inflammatory stimulus. The acid was able to reverse an established carrageenan induced inflammatory response when administered 2 h after induction. Daily administration of mansumbinoic acid at a single dose level (1.5 x 10(-4) mol kg 1) significantly reduced joint swelling in adjuvant arthritis in rats. The results indicated that this compound is worthy of further investigation as an anti-inflammatory drug. PMID- 8441774 TI - Effect of ginseng on plasma levels of ethanol in the rat. AB - The effect of red ginseng extract on the disposition of ethanol was studied in male Fischer 344 rats. Blood was drawn from the tail vein before and at 0.5, 1, 2, 3, 4, and 5 hours after dosing rats orally with aqueous ginseng (200 mg/kg), or an equivalent volume of water, followed immediately by 50% ethanol orally (3.2 g/kg) or intraperitoneally (1.5 g/kg). When the ethanol was administered orally, the mean area under the plasma concentration-time curve (0-->5 h) of ethanol was 21.0% less in the ginseng-treated rats than in the control rats. When the ethanol was administered intraperitoneally, there was no significant difference between ginseng-treated and control rats in area under the plasma concentration-time curve. The results show that plasma levels of ethanol are lower when the ethanol is administered orally with ginseng than when it is administered alone, but that orally administered ginseng has no effect on plasma levels of ethanol administered intraperitoneally. PMID- 8441775 TI - Quality of Ginkgo preparations. AB - A survey of known and of recently isolated constituents from Ginkgo leaves is given. The structures of flavonoids and terpene lactones which are considered to be the active compounds as well as their qualitative and quantitative determination in Ginkgo leaves and phytomedicines are presented. In the case of flavonoid analysis three selective methods worked out in our laboratories are described. The quality control of terpene lactones is discussed on the basis of a recently published paper. Finally, the standardization methods used for the quality control of Ginkgo preparations as well as the question as to whether or not phytomedicine generics--so called "phytogenerics"--exist, is discussed. PMID- 8441776 TI - Feverfew and vascular smooth muscle: extracts from fresh and dried plants show opposing pharmacological profiles, dependent upon sesquiterpene lactone content. AB - Preparations of fresh or dried feverfew (Chrysanthemum parthenium) are widely consumed in the U.K. as a remedy for arthritis and migraine, but the pharmacological basis for this has not been established. We have, therefore, compared the properties of extracts of fresh plants with those of dried powdered leaves available commercially from health food shops. The two extracts differed radically in their content of alpha-methylbutyrolactones and in their pharmacological profile when tested in vitro on the rabbit aortic ring and rat anococcygeus preparations. Extracts of fresh leaves caused does- and time dependent inhibition of the contractile responses of aortic rings to all receptor acting agonists so far tested; the effects were irreversible and may represent a toxic modification of post-receptor contractile function in the smooth muscle. The presence of potentially -SH reactive parthenolide and other sesquiterpene alphamethylenebutyrolactones in these extracts, and the close parallelism of the actions of pure parthenolide, suggest that the inhibitory effects are due to these compounds. In contrast , chloroform extracts of dried powdered leaves were not inhibitory but themselves elicited potent and sustained contractions of aortic smooth muscle that were not antagonised by ketanserin (5-HT2 receptor antagonist). These extracts did not contain parthenolide or butyrolactones according to a chemical-HPLC assay, We conclude that there are marked differences in the pharmacological potency and profiles between preparations from fresh and dried feverfew and that this may relate to their lactone content. As the effects of the lactones are potentially toxic, it will be necessary to compare the clinical profiles and side effects of preparations obtained from the two sources. PMID- 8441777 TI - The analgesic activity of Hedyosmum bonplandianum: flavonoid glycosides. AB - Kaempferol 3-O-[alpha-L-rhamnopyranosyl (1-->6)-beta-D-glucopyranoside] and kaempferol 3-O-[beta-D-glucopyranoside] were isolated from the leaves of Hedyosmum bonplandianum H.B.K. (Chloranthaceae), which is used in Colombian folk medicine as an analgesic. The n-butanol extract and the glycosyl flavonoids isolated exhibited significant analgesic activity in mice. PMID- 8441778 TI - The effects of tannic acid on serum lipid parameters and tissue lipid peroxides in the spontaneously hypertensive and Wistar Kyoto rats. AB - The effects of tannic acid or its vehicle (normal saline) on blood pressure, blood lipid parameters, liver and kidney malonaldehyde (MDA) levels were investigated in the spontaneously hypertensive rats (SHR) and the normotensive Wistar Kyoto rats (WKY). When tannic acid dissolved in normal saline, was injected intraperitoneally (i.p.) twice a week at a single dose of 15 mg/rat/injection (30 mg/week) for a period of 10 weeks to the SHR, the serum total cholesterol (TC), low density lipoprotein cholesterol (LDLC), and triglycerides (TG) were significantly lower compared to the vehicle-treated SHR. However, there was no significant difference in the high density lipoprotein cholesterol (HDLC) concentration. Administration (i.p.) of tannic acid to the WKY did not cause any significant effects on the serum TC, LDLC, and TG levels. The HDLC concentration of the tannic acid-treated WKY was significantly higher than in the vehicle-treated WKY. The LDLC/HDLC ratio was significantly lowered compared to their respective controls for both strains of rats. When tannic acid was administered (i.p.) by osmotic pumps over a 13 day period (30 mg tannic acid/week), the kidney MDA level in the SHR was found to be significantly lower than in the vehicle-treated SHR. The liver MDA level was not significantly different between the treated and control rats. In the WKY, MDA was detected in trace amounts in the kidneys of both the control and treated rats. There were appreciable amounts of MDA detected in the liver of the control and treated rats but these were not significantly different from one another.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441779 TI - Effects of agarwood extracts on the central nervous system in mice. AB - Agarwood (Jinkoh in Japanese) is an Oriental medicine for use as a sedative. Neuropharmacological studies have been conducted with the extracts of petroleum ether, benzene, chloroform, and water from agarwood (Aquilaria sp.; probably Aquilaria malaccensis Benth.) in mice. The benzene extract showed a reducing effect in spontaneous motility, a prolonging effect on hexobarbiturate-induced sleeping time, a hypothermic effect in terms of rectal temperature, and a suppressive effect on acetic acid-writhing by oral administration. Fr. 1 of the three fractions which were obtained from the benzene extract by column chromatography was found to produce more positive effects on these neuropharmacological tests than the original benzene extract. These facts suggest that the benzene extractable compounds of agarwood possess potent central nervous system depressant activities. PMID- 8441780 TI - Prevention of galactosamine-induced hepatic damage by picroliv: study on bile flow and isolated hepatocytes (ex vivo). AB - Picroliv, a standardized extract from the plant Picrorhiza kurrooa containing active constituents, showed a significant dose dependent (3-12 mg/kg p.o. x 7) protective activity against galactosamine-induced hepatic damage in rat as evaluated on the isolated hepatocytes (ex vivo) preparation. It markedly increased the percentage of viability of hepatocytes. It also restored the galactosamine-induced changes in the levels of enzymes (GOT, GPT and alkaline phosphatase) both in isolated hepatic cells as well as in serum. In addition, picroliv possessed a marked anticholestatic effect. Picroliv was found to be more potent than silymarin, a standard hepatoprotective agent. PMID- 8441781 TI - Isolation and biological effects of 7-O-methyleriodictyol, a flavanone isolated from Artemisia monosperma, on rat isolated smooth muscles. AB - The isolation for the first time from the genus Artemisia (Compositae) of the known flavanone, 7-O-methyleriodictyol (7-methoxy-5,3',4'-trihydroxy-flavanone), its identification, and its biological effects on rat isolated smooth muscles are described. 7-O-Methyleriodictyol (10(-7) M to 3 x 10(-4) M) caused concentration dependent inhibition of the amplitude of the phasic contractions and reduced the tone of the ileum, the uterus, and the urinary bladder. It also caused relaxation of the phenylephrine-precontracted pulmonary artery and the acetylcholine precontracted trachea. The flavanone also shifted to the right the acetylcholine concentration-effect curve on the ileum and the oxytocin concentration-effect curve on the uterus. The maximum contractions induced by acetylcholine or oxytocin were also inhibited by 7-O-methyleriodictyol. These antispasmodic effects are partly consistent with the use of A. monosperma in folk medicine for certain gastrointestinal disorders. PMID- 8441782 TI - Biochemical and morphological alterations of macrophages and spleen cells produced by antitumor polysaccharide from Acanthopanax obovatus roots. AB - Acanthopanax obovatus polysaccharide (AOPS) administrated intraperitoneally (i.p.) resulted in the augmentation of phagocytosis and the chemiluminescence in peritoneal macrophages of mice. Binding of the third component of complement (C3) cleavage products to the receptors on peritoneal macrophages was enhanced by AOPS. The C3 conversion in human serum was increased by AOPS in vitro treatment. When given i.p., AOPS led to the enhancement of spleen weight, spleen cell number, and plaque-forming cells. It was also found that after in vivo administration AOPS not only enhanced the synthesis of DNA and protein but also promoted the mitogenic responses of spleen cells. The morphological observation of spleens indicated that AOPS augmented the transformation from lymphocytes to plasma cells. AOPS inhibited the growth of mouse solid Sarcoma-180 and prolonged the survival time significantly. These results suggest that AOPS is an effective biological response modifier and its antitumor activity is related to its immunopotentiating effects. PMID- 8441783 TI - Strychnopentamine, a potential anticancer agent. AB - We analysed the effects of strychnopentamine, an alkaloid isolated from Strychnos usambarensis, on an Ehrlich ascites tumor growing in the mouse after inoculation. Four subcutaneous injections of 1.5 mg strychnopentamine (1 per day) induce a significant decrease of the number of tumor cells and a significant increase of the survival of the treated mice. Observed side effects are partial haemolysis and some liver damage. PMID- 8441784 TI - Antispasmodic activity of benzylisoquinoline alkaloids analogous to papaverine. AB - In vitro, reticuline, norarmepavine, coclaurine, and papaverine competitively antagonize the uterine muscular contractions induced by acetylcholine and calcium. The antagonism is more efficient for the alkaloid coclaurine which is even stronger than papaverine. The pA2 values obtained with each of the four alkaloids for both agents, acetylcholine and calcium, respectively, were as follows: reticuline (5.35 and 4.81), norarmepavine (5.55 and 4.09), coclaurine (7.42 and 6.91), papaverine (5.32 and 6.23). The two components, phasic and tonic, of the response of the vas deferens to potassium are reduced by the four alkaloids. The reduction is greater for the tonic phase, with the following IC50 values: reticuline 474 microM, norarmepavine 101 microM, coclaurine 68.9 microM, and papaverine 14.3 microM. The antispasmodic activity of the three alkaloids, similar to papaverine, is related to an inhibiting effect of extracellular calcium, an intracellular effect, or both. PMID- 8441785 TI - Chemical composition and antimicrobial activity of essential oils of Jasonia candicans and J. montana. AB - The essential oils of the aerial parts of Jasonia candicans and J. montana were analyzed by gas chromatography-mass spectrometry (GC/MS) technique. Of twenty-one components identified in the volatile oil of J. candicans, intermediol was the main constituent. Fifty-eight components were characterized in the essential oil of J. montana. Camphor, borneol, bornyl acetate, chrysanthemol, intermediol, and 1,8-cineole were the major constituents in this oil. The two oils showed antibacterial activity against Bacillus subtilis. They also showed a marked antifungal activity against Trichophyton mentagrophytes, Cryptococcus neoformans, and Candida albicans. PMID- 8441786 TI - Saponins in the leaves of birch? Hemolytic dammarane triterpenoid esters of Betula pendula. AB - Three hemolytic dammarane triterpenes, esterified with malonate at C-3 and acetate at C-12, were isolated from the leaves of Betula pendula. Their structures were elucidated by chemical and spectroscopic means. Former reports on the presence of saponins in birch leaf extracts could not be confirmed. The hemolytic activity of the extracts, which was ascribed to saponins, is caused by the dammarane esters instead. A fraction containing a mixture of the dammarane esters did not exhibit diuretic activity when tested p.o. in male Wistar rats. PMID- 8441787 TI - Bioactive single-ring acetogenins from seed extracts of Annona muricata. PMID- 8441788 TI - Contribution to the study of Salvia lavandulifolia essential oil: potential toxicity attributable to sabinyl acetate. PMID- 8441789 TI - Validation in the clinical theory of psychoanalysis. A study in the philosophy of psychoanalysis. PMID- 8441790 TI - Quality of life measurements in chronic disorders. AB - The political or ecological concept of quality of life refers to irreplaceable aspects of life. The health-related quality of life concept has the same impact of considering the irreplaceable (idiographic) aspects of treatment outcome in patients with chronic disorders. When comparing the different attempts to measure quality of life, two main approaches have been considered, namely a multi dimensional view of medical disorders and a global view of outcome of treatment. Both approaches have been discussed at the same level of measurement, i.e. how the patient considers the various components. A dialectic procedure has been followed: quality of life data versus 'raw' health data; idiographic versus nomothetic scales; index versus profile statistics; generic versus disease specific measurements. PMID- 8441791 TI - Nonverbal and verbal emotional expression and health. AB - The spontaneous nonverbal expression of emotion is related to immediate reductions in autonomic nervous system activity. Similar changes in specific autonomic channels occur when individuals are encouraged to verbally express their emotions. Indeed, these physiological changes are most likely to occur among individuals who are either verbally or nonverbally highly expressive. These data suggest that when individuals must actively inhibit emotional expression, they are at increased risk for a variety of health problems. Several experiments are summarized which indicate that verbally expressing traumatic experiences by writing or talking improves physical health, enhances immune function, and is associated with fewer medical visits. Although less research is available regarding nonverbal expression, it is also likely that the nonverbal expression of emotion bears some relation to health status. We propose that the effectiveness of many common expressive therapies (e.g., art, music, cathartic) would be enhanced if clients are encouraged to both express their feelings nonverbally and to put their experiences into words. PMID- 8441792 TI - Psychosomatic view of endocrine disorders. AB - This review is concerned with the clinical and research implications of psychosomatic research in endocrinology. A possible role of life events in the pathogenesis of endocrine disease, the psychological distress associated with acute illness, and the issue of quality of life in clinical endocrinology are surveyed. In particular, the psychosomatic aspects of Cushing's syndrome, Addison's disease, hyperthyroidism, hypothyroidism, hyperprolactinemia, acromegaly, growth hormone deficiency, and hirsutism are considered. PMID- 8441793 TI - Double-blind, placebo-controlled study of S-adenosyl-L-methionine in depressed postmenopausal women. AB - S-adenosyl-L-methionine (SAMe) is a naturally occurring substance which is a major source of methyl groups in the brain and has been found in previous studies to be an effective antidepressant. The aim of this study was to assess the efficacy of oral SAMe in the treatment of depressed postmenopausal women in a 30 day double-blind placebo-controlled randomized trial. During the course of the study, 80 women, between the ages of 45 and 59, who were diagnosed as having DSM III-R major depressive disorder or dysthymia between 6 and 36 months following either natural menopause or hysterectomy, underwent 1 week of single-blind placebo washout, followed by 30 days of double-blind treatment with either SAMe 1,600 mg/day or placebo. There was a significantly greater improvement in depressive symptoms in the group treated with SAMe compared to the placebo group from day 10 of the study. Side effects were mild and transient. PMID- 8441794 TI - A Pain Rating Scale and a Pain Behavior Checklist for clinical use: development, norms, and the consistency score. AB - A Pain Rating Scale [PRS] and a Pain Behavior Checklist [PBC] were developed for use during a clinical pain interview. Norms were based on 395 chronic pain patients referred for pain management. The PRS obtained ratings of present pain, and worst and least pain during the previous 30 days. The PBC recorded 16 pain behaviors during the 45- to 60-min interview. Normative data were given for seven measures: (1) worst pain rating, past month; (2) least pain rating, past month; (3) present pain rating; (4) difference between worst and least pain ratings; (5) pain behavior score; (6) total pain score (based on Nos. 1, 2, 3, and 5), and (7) consistency score. The consistency score reflects the agreement (or discrepancy) between the pain behavior and present pain ratings. A moderate overall relationship was found between pain behavior and present pain ratings (r = 0.46, p < 0.001). The frequency of good agreement between pain behavior and present pain ratings was unaffected by sex, race, age, pain site, type of injury, duration of pain, legal representation, and evaluating psychologist; but it varied markedly with conscious symptom magnification. Patients seen as consciously exaggerating pain (n = 127) gave higher pain ratings (all p values < 0.001); and had frequent (64.6%) discrepancies between their pain report and pain behavior compared to others (14.2%). The report of present pain was unrelated to pain behavior for conscious exaggerators (r = 0.04, NS); in contrast there was a moderately high relationship for other patients (r = 0.68, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441795 TI - [Psychosocial factors in carcinogenesis: on the problem of the so-called cancer prone personality]. AB - Without distinguishing between the heterogeneous types of the disease which are implied in the term "cancer" a stereotype--the cancer-prone personality--is regarded as the essential cause of the disease. Their striking characteristics are quoted as follows: depressive mood, social conformity, restrained expression of needs and emotions, reduced perception of physical symptoms, etc. In a prebioptical prospective study, basing on semi-structured interviews carried out at two different points of time, with 230 women with breast tumours and 95 patients with a suspected lung cancer, the theory of a psychosocial cancer ethiology was examined with regard to the following aspects: do the psychological phenomena observed reflect a premorbide personality structure or do they represent reactions to the disease? Is it possible to register personality related phenomena in the preventive behaviour and are there specific differences in the perception of the symptoms? Through this quasi-experimental approach it was possible to distinguish between the influence of the personal expectancy concerning the diagnosis and the effect of the actual disease. This way it was proven that psychological phenomena of cancer patients are to be understood as the result and not as the cause of the disease. PMID- 8441796 TI - [Anxiety neurosis--avoidant behavior--depression. A comparison between panic disorder and generalized anxiety disorder]. AB - 30 patients with "Anxiety disorder" were investigated with regard to their psychosocial experiences, their family history, the course of their illness, and their interpersonal relationships using a semi-structured interview. Patients with panic disorder significantly more frequently reported real fright of a parent than did patients with generalized anxiety disorder. Both groups showed a high degree of secondary depression and avoidance behavior in the course of their illness. Chronic anxiety was more frequent in patients with generalized anxiety disorder. The difference in the perception and judgement of anxiety clearly demonstrates the significance of attribution. Since the patient with panic disorder externalizes his anxiety, he has periods of complete remission, whereas the patient with generalized anxiety disorder internalizes his anxiety, thus experiencing it as an ego-syntonic feature, with which he cannot cope. PMID- 8441797 TI - [Psychometric assessment of defense mechanisms: correlation between questionnaire and expert rating. Initial study of validity]. AB - Within the limits of an epidemiological longitudinal field survey on prevalence and course of psychogenic disorders a high-risk-population suffering from medical psychogenic impairment was investigated. The study was conducted in order to verify an etiological multi-level-model of psychogenic disorders in relation to the socialempiric variables "critical life events" and "social support" as well as the depth psychological oriented construct "personality". Besides other instruments a self rating scale based on Vallant's hierarchical model of defense, i.e. the german adaptation of the DSQ (Defense Style Questionnaire) of Bond and coworkers, was used for the accurate measurement of relevant personality parameters. Although defense processes predominantly work unconscious, manifestations of defense mechanisms could be measured indirectly by means of the rating scale. Its essential dimensions separated clinical patients from a group of healthy controls. Furthermore an immature organisation of defense was found to be related to psychogenic impairment. Concerning self- and expert-rating a significant correlation between "immature defense" and the defense mechanisms "schizoid phantasy", "projection" and "acting out" was proved. PMID- 8441798 TI - [Experiences with psychosocial liaison service on oncologic units of an acute clinic]. AB - Within the last years psychosocial care in acute medicine has become more and more important. Therefore different conceptional structures are discussed to optimize the integration into primary care medicine, especious psychosomatic or psychosocial consultation and liaison services. Having resumed the concepts and practice of psychosocial care in oncology this paper describes a psychosocial liaison service accompanying a research project in psychooncology. The representation focuses the experience with psychosocial care of cancer patients over the last three years. Based on a systematic clinical documentation the activities are described with regard to psychosocial indication, patient assignment, patients needs during acute treatment and the different kinds of psychosocial interventions applied. The experiences are evaluated regarding the target groups (patients, relatives, medical staff) and associated problems of cooperation and organisation met with medical staff. Finally needs, possibilities and limits of psychosocial liaison services are discussed comparing the experiences with others reported in the literature. PMID- 8441799 TI - [Prenatal acoustic perception--a review of the literature from the psychosomatic viewpoint]. AB - In a critical overview on the empirical results to the problem of "Prenatal Hearing" the authors show the development of investigation in the last sixty years. Some conclusions on developmental psychosomatic aspects are discussed. PMID- 8441800 TI - [Ultrasonic imaging artifacts. Physical bases]. AB - This review describes frequently visualized and clinically relevant artifacts in ultrasound imaging. The imaging artifacts are categorized by their underlying physical or technical causes, such as: multiple reflections, non-linear propagation direction of the sound, sound beam diameter and pulse length, attenuation, interference, range ambiguity and propagation speed. Examples are given, and procedures that help to minimize imaging artifacts are discussed. PMID- 8441801 TI - [Pseudolesions in liver sonography]. AB - Several common hepatic ultrasound pseudolesions are presented that may closely resemble pathological conditions. The majority of these pitfalls is caused by normal anatomic structures, anatomical variants of the liver or the perihepatic regions, and benign alterations of the echotexture of the liver. Exact knowledge and a precise scanning technique by an experienced sonographer are essential to avoid mistaking such findings for true liver disease. In some instances (especially when dealing with anatomical variants) computed tomography is also helpful. PMID- 8441803 TI - [Possibilities of error in sonography of the pancreas and spleen]. AB - Sonography plays an essential role in imaging suspected disease in the pancreas and spleen. A variety of different factors, such as artifacts, the close anatomical relationship of the pancreas to other intestinal organs, variant anatomy, and the well-known effect of the skill and experience of the sonographer may cause diagnostic difficulties. In this article, we discuss potential pitfalls and differential diagnoses in ultrasonographic imaging of the pancreas and spleen. PMID- 8441802 TI - [Possibilities of error and pitfalls in sonography of the gallbladder and bile ducts]. AB - Ultrasound has a primary role in the imaging of biliary disease. Often the diagnosis is straightforward, but in this article the emphasis is placed on unusual and uncommon diseases, variant anatomy and artifacts that may present diagnostic challenges. The pitfalls and differential diagnosis in sonographic imaging of cholecystolithiasis, intraluminal gallbladder echoes, gallbladder wall thickening, artifacts of the gallbladder wall, pericholecystic fluid collections, bile duct dilatation and intraluminal bile duct echoes are discussed. PMID- 8441804 TI - [Possibilities of error in the sonographic diagnosis of the kidneys]. AB - In renal sonography pitfalls and differential diagnoses are very common. Typical pitfalls are presented in a pictorial essay and are discussed. PMID- 8441805 TI - [Gadolinium-DTPA enhanced MRT in the evaluation of the healing of autologous patellar ligament transplants for anterior cruciate ligament reconstruction]. AB - Eighteen patients with autologous patellar tendon transplant for reconstruction of the anterior cruciate ligament were examined postoperatively. The time between operation and MR study was up to 3 weeks in ten patients, between 3 and 35 weeks in three patients and more than 35 weeks in five patients. In all patients, Gd DTPA enhancement on the surface of the ligamentous transplant was visualized. This enhancement was between 1 and 10 mm thick. In all patients, complete stability of the knee joint was achieved, postoperatively. In 15 patients flexion and extension were normal at the postoperative investigation. Three patients had a limitation of knee movement. In these MR studies, significant hyperplasia of the synovial membrane of the entire joint was diagnosed, explaining the persisting problems. Gd-DTPA-enhanced MR of the knee joint allows non-invasive documentation of remodelling following a patellar ligament transplant and possible complications. PMID- 8441806 TI - [Radioactivity of bone cement]. AB - A total of 14 samples of different types of bone cement from five different manufacturers were examined for their radioactivity. Each of the investigated bone cements showed a low radioactivity level, i.e. between < 1 and 100 Bq/kg. The content of U-238 and K-40 always was below the limit of detection (< 1-< 10 Bq/kg). Significant differences were detected in the amount of Ra-226, Pb-210, and Ra-228 detected between different samples of the same product from the same manufacturer, as well as between various types of cements. The highest radioactivity level was measured for Ra-226. Although stochastic radiation effects can not totally be excluded, it is extremely unlikely that the small amount of radioactive substances additionally transferred into the body by the bone cement has negative effects on the recipient's organism or on the fate of the alloplastic implant: "The risk factor and extrapolation in a low dosage range ... do not lead to an underestimation but more likely to an overestimation of the radiation hazard" [18]. PMID- 8441807 TI - [The physician as patient]. PMID- 8441808 TI - [A progressive abdominal pain with a palpable resistance in the right lower abdomen]. PMID- 8441809 TI - [Comments on the article by B. Maier et al. Iotrolan versus Iopamidol. A controlled double-blind study in lumbar myelography]. PMID- 8441810 TI - Hydration and heat stability effects on protein unfolding. AB - In summary, the thermal denaturation of proteins has been elucidated in terms of the chain free energy and the hydration free energy as follows. (1) Method to calculate the unfolding free energy. The free energy of unfolding consists of two contributions: the hydration around the molecule, and the intramolecular interactions. A method to calculate the free energy of hydration from the accessible surface area (ASA) of the constituent atomic groups in a protein has been developed. This assumes a proportionality between the free energy and the ASA, where the proportional constants were determined by least-squares fitting to the experimentally derived thermodynamic data on small molecules. Similarly, the free energy of unfolding for the chain in vacuo can be also calculated from the ASA, using the unfolding thermodynamics derived from the experimental data of the ten proteins. (2) Thermodynamics of protein unfolding predicted from the three dimensional structures and from the amino acid content in proteins. First, our method is applied to predict the thermodynamics of protein unfolding from the X ray structure. The predicted values of four test proteins agree well with the experimentally derived values. It also accounts for the temperature dependence of the free energy and of the enthalpy upon unfolding for 14 proteins. Second, this method is applied to the helix-coil transition of short peptides of poly(L-Ala)20 and Ac-(AAAAK)3A-NH2. The calculated enthalpy change is close to the experimental values for poly-L-Lys and poly-L-Glu. Since delta Hcu at 25 degrees C significantly contributes to delta Gu, the helix formation is enthalpy-driven through interactions in the chain. Third, the method is applied to predict the unfolding thermodynamics of a globular protein from its amino acid content. It also accounts for the temperature dependence of the free energy of unfolding for the 14 proteins. The agreement between the experimental and the calculated values by this method for the 14 proteins is not so different from those obtained with the three-dimensional structures. Fourth, the values of delta Cpu for 14 proteins may be closely approximated to the predicted values of delta Cp,hu. The delta Cp,hu value in a protein consists of the major contribution from the hydrophobic and the aromatic residues, and the minor one from the hydrophilic residues. (3) Dominant free energies in protein folding.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8441811 TI - Derivation of locally accurate spatial protein structure from NMR data. PMID- 8441812 TI - Myelinated nerve fibres in the CNS. AB - (1) Lamellated glial sheaths surrounding axons, and electrogenetically active axolemmal foci have evolved independently in widely different phyla. In addition to endowing the axons to conduct trains of impulses at a high speed, myelination and node formation results in a remarkable saving of space and energy. This is particularly important in the CNS, where space is restricted. Unlike the PNS, most CNS axons are myelinated, and several axons may be myelinated by a single cell. This adds further economy of space and energy. On the other hand the high level of complexity of the CNS white matter makes it vulnerable. There are several different kinds of disease affecting myelinated fibre tracts, particularly with respect to CNS white matter. (2) The CNS node of Ranvier presents a more complex structure the larger the fibre. The constricted nodal axon is encircled by perinodal astrocytic processes which contain large gliosomes and emit delicate processes towards the nodal axolemma. One astrocyte may project to several nodes. The node gap contains a polyanionic extracellular material. (3) Lamellated myelinoid bodies are frequent along paranodes of large myelinated CNS fibres. These bodies probably form through budding off from the paranodal myelin sheath. Similar bodies are seen inside astrocytes and microglia. The observation that these bodies are Marchi-positive and argyrophilic, and the presence of acid phosphatase activity around myelinoid bodies inside microglia suggests that they might represent degenerating myelin quanta, involved in the turnover of large myelin sheaths. This putative quantal release and breakdown of myelin material must be compensated for by a production of new myelin at other sites. Therefore, myelination may be viewed as a process that continues throughout life. (4) Biochemical analysis of a sub-cellular fraction enriched in myelinoid bodies shows that these bodies have a composition basically similar to that of myelin. However, breakdown products of myelin constituents, as well as exotic high molecular substances, not present in conventional myelin, can also be found. In addition, the myelinoid body fraction contains proteolytic activity. Studies using isotope labelling of myelin proteins show a source-product relation between myelin and myelinoid bodies. Altogether these data strongly support the hypothesis that myelinoid bodies reflect the catabolic side of myelin turnover. (5) Axons in the nerve fibre layer of the adult rat retina are all unmyelinated, although their diameters range up to over 2 microns. These axons exhibit focally differentiated axolemmal areas. At these sites the axolemma presents a dense undercoating with externally associated Muller cell processes or astrocytic processes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8441813 TI - Two types of inhibitory postsynaptic potentials in the hypoglossal motoneurons. PMID- 8441814 TI - [Clinical comments on female homosexuality]. AB - In psychoanalytic theory, homosexual women are regarded as being possessed by violent hatred of the mother. They are held to identify with the male or the phallic and to display an absence of "normal" femaleness. Their attendant immaturity makes them incapable of love. The author takes issue with the assumption that normality is synonymous with mature, reciprocal heterosexuality. With reference to a case study of a homosexual woman, she traces the structure of a lesbian love relationship. The patient is the involuntary witness of sexual intercourse between the parents. The mixture of alarm and excitement which this arouses sparks off female desires that revive early libidinous experiences with the mother. The girl desires her mother, without however identifying with the father. In her later relationships with women she does not relate to her partners as a disguised man but as a woman. Identification with the father serves as a defence against the desire for-and the fear of-identification at a female level. PMID- 8441816 TI - [Problems and strategies of qualitative psychotherapy research in clinical institutions]. AB - The neglect of institutional codetermination in therapeutic decisions is exposed as a desiderative in research. Qualitative approaches as developed in the social sciences must come to grips with the social unconscious institutional procedures; therapy is proposed to be considered as a social event. Thus Reality Work is viewed as field and object of qualitative research in clinical institutions, a concept close to ethnographic and social constructionist approaches. The generative techniques (as dissonance reduction, narrative transformations and selection of rules of discourse) institutions use for the establishment of their social-emotional integration are illustrated by examples; they are instruments to produce a processible image of the patient. Images thus generated rule treatment, they can be formulated as metaphors und looked for at different levels. PMID- 8441815 TI - [Psychoanalytic interventions: reflections on form]. AB - The question of the form of analytic interventions is an important one in the context of the theory of analytic techniques. On the basis of 4 brief case descriptions, the author demonstrates that certain therapeutic situations call for a choice of language which echoes that employed by the analysand, thus representing something akin to the latter's inner voice and attaining a graphic, "dramatic" quality which facilitates contact with the archaic sides of the patient and also identification of regressive tendencies and/or severe communicative defects. In other situations it may be necessary to employ neutral, "objective", scientific parlance, for example when the transference of the analysand is openly erotic or hostile in character. PMID- 8441817 TI - [Kekule's dream. Additional observations on the "benzol ring"]. AB - 20 years ago, Alexander Mitscherlich published in this journal a brief psychological study of the famous dream the chemist Friedrich August Kekule had immediately before putting forward his representation of the benzene molecule in the "Kekule formula". Mitscherlich (among whose forebears a number of prominent chemists figured) interpreted the dream as an expression of a frustrated and repressed sexual desire. The present author, by contrast, favours an interpretation which shifts the focus away from the suggestive power of the dream image-a snake biting its own tail-and sees Kekule's dream production as a reflection of the psychic effort it cost him to ward off latent feelings of guilt associated with the early death of his wife and to alleviate scruples of conscience about his own achievement. PMID- 8441818 TI - Peptide YY in the mammalian pancreas: immunocytochemical localization and immunochemical characterization. AB - Peptide YY (PYY) was demonstrated by immunochemical and/or immunocytochemical methods in endocrine cells in the pancreas of adult mice, rats, guinea-pigs, cats, dogs, pigs and cows. In the pancreas of mouse and rat, immunoreactive PYY was observed in a major subpopulation of the glucagon cells (splenic lobe of the pancreas); immunoreactive PYY also occurred in a subpopulation of the pancreatic polypeptide (PP) cells (duodenal lobe), and in a few extra-insular endocrine cells dispersed throughout the pancreatic parenchyma. In the pancreas of cat, dog and pig immunoreactive PYY was found to coexist with PP, but not with glucagon. Radioimmunoassay (RIA) revealed PYY-like material in extracts of pancreas (and colon) of all the species examined. The highest concentrations were found in the pancreas of cat and mouse; moderate amounts were found in the rat and only small amounts were detected in guinea-pig and pig. The concentrations in the pancreas were uniformly much lower than those in the colon. Analysis by high performance liquid chromatography (HPLC) showed that the PYY-immunoreactive material from pancreas (and rat colon) had an elution profile very similar to that of synthetic PYY, and distinct from that of PP and neuropeptide Y. PMID- 8441819 TI - Octreotide (SMS 201-995) inhibits the growth of colon peritoneal carcinomatosis in BDIX rats. AB - In order to assess the effect of octreotide, a somatostatin analogue, on the growth of colon peritoneal carcinomatosis, 20 BDIX rats were injected i.p. with 1 x 10(6) colon cancer cells (DHD/K12 tumor cell line) and received octreotide, 65 micrograms/kg s.c. every 12 h (n = 10) or saline (n = 10) for 42 days, starting 3 days after tumor cell injection. Animals were killed at the end of the treatment. The mean volume of ascites was lower in the octreotide group (33.7 +/- 7.6 ml), than in the control group (67.5 +/- 16.3 ml; P < 0.05). The extent of peritoneal carcinomatosis (in five classes according to a previously published classification) was lower in the octreotide group (P < 0.05). Cell proliferation, using the BrdU technique, was markedly inhibited by octreotide (labeling index of tumor cells: 17.0 +/- 0.6% vs. 26.3 +/- 2.2% in controls, P < 0.001). No significant decrease in labeling index was observed in normal colonic mucosa. Two subtypes of somatostatin receptors were found in all tumors, using the 30F3 monoclonal antireceptor antibody. KD and Bmax values were not significantly different in the octreotide and control groups: high affinity, low capacity receptors (KD = 1.4 x 10(-10) M and 0.7 x 10(-10) M, respectively; Bmax = 3.8 and 2.9 pmol/mg protein, respectively); low affinity, high capacity receptors (KD = 1 +/- 0.2 x 10(-9) M and 5.5 +/- 0.05 x 10(-10) M, respectively; Bmax = 27.8 +/- 0.1 and 22.8 +/- 0.05 pmol/mg protein, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441820 TI - Characterization of gastrin/CCK receptors on gastric carcinoid tumor membrane of Mastomys natalensis. AB - Recently, we identified the specific binding site for gastrin on the gastric carcinoid tumor of Mastomys (Praomys) natalensis. In this study, precise characterization of the gastrin binding site on these tumors was performed. Both 125I-human gastrin I (gastrin) and 125I-CCK-8 bound specifically to the cell membrane, and Scatchard analysis revealed a high affinity binding site for each ligand with similar Kd and Bmax values. The specific binding of both 125I-gastrin and 125I-CCK-8 was displaced in a concentration-dependent manner by various related peptides with a relative potency order of CCK-8 > or = gastrin < des(SO3)CCK-8. In addition, L364,718 as well as L365,260 displaced the binding of both ligands with similar potencies. Furthermore, not only gastrin but also CCK-8 increased [Ca2+]i in these tumor cells, the action of both being inhibited by L364,718 as well as by L365,260 (10(-7) M). These results suggest that the carcinoid tumor of Mastomys possesses a high affinity gastrin/CCK binding site coupled to the increase of [Ca2+]i. PMID- 8441821 TI - Effect of difluoromethylornithine on atrial natriuretic peptide in rat atria. AB - Polyamines are aliphatic cations known to have a role in cellular growth and differentiation. In this study, difluoromethylornithine (DFMO), an inhibitor of polyamine synthesis, was used to investigate its effect on atrial natriuretic peptide (ANP) in atria of rat. The rats were given DFMO (2%) in drinking water for 10 days and three intraperitoneal administrations (200 mg/kg), 24, 18 and 1 h prior to experiment. Radioimmunoassay of ANP in atrial extracts indicated that DFMO treatment increased ANP contents of atria. ANP from atrial extracts was immunoprecipitated using ANP antibody and the immunoprecipitate was resolved and detected by SDS-PAGE and Western blotting. The predominant ANP peptide in both control and DFMO group migrated at 17 kDa. The synthesis of ANP was studied following the intravenous administration of [35S]methionine. ANP in atrial extracts was immunoprecipitated by ANP antibody. The incorporation of ANP into control and DFMO group peaked at 30 min and returned to a basal level by 60 min. DFMO decreased the incorporation of [35S]methionine into ANP. At 30 min following the administration of [35S]methionine, putrescine restored the synthesis of tricholoroprecipitable atrial proteins, but had no effect on the synthesis of ANP. At 60 min following, the amount of labeled ANP in DFMO + putrescine-treated group was significantly lower than that in DFMO group. These results indicate that polyamines influence both the synthesis and secretion of ANP. PMID- 8441822 TI - Importance of cholecystokinin in peptide-YY release in response to pancreatic juice diversion. AB - It is generally accepted that peptide-YY (PYY), an ileocolonic peptide, is released by luminal nutrients and exogenous cholecystokinin (CCK). The importance of luminal nutrients as major PYY releasers was recently challenged when significant increases in plasma PYY were observed in response to pancreatic juice diversion in rats free of luminal nutrients. These recent data raise questions concerning the potential mediators of PYY release. This study was undertaken therefore to determine the role of endogenous CCK and the effects of exogenous caerulein, secretin and bombesin on PYY release. Male Wistar rats prepared with pancreatic, biliary, duodenal and jugular vein cannulae were used 4-7 days postoperatively. Pancreatic juice diversion significantly increased pancreatic volume and protein output with concomitant increases in plasma CCK and PYY concentrations. During pancreatic juice diversion, infusion of MK-329, a CCK receptor antagonist, did not affect CCK release but completely abolished pancreatic volume and protein output and PYY release. The intraduodenal infusion of SBTI significantly stimulated pancreatic secretion and CCK release without any effect on PYY release. Furthermore, infusions of the CCK analog, caerulein, secretin and bombesin had no effect on PYY release. These results suggest the involvement of endogenous CCK in PYY release but this mediation seems to necessitate the participation of other as yet unknown factors since exogenous caerulein, secretin or bombesin cannot induce PYY release when given alone. PMID- 8441824 TI - Priority food safety issues for the year 2000. PMID- 8441823 TI - Atrial natriuretic factor modifies bile flow and composition in the rat. AB - The effects of atrial natriuretic factor (ANF) on bile secretion were studied in the rat. ANF was injected 'in bolus' (5.0 micrograms/kg) every 30 min into the jugular vein. The common bile duct was cannulated and bile samples were collected every 30 min for 120 min. Systemic blood arterial pressure was registered before and after the administration of ANF. Results showed that ANF decreased bile flow and the excretion rate of sodium, potassium, chloride, bile acids, cholesterol and proteins. On the other hand, it increased pH and the excretion of bicarbonate and calcium. As ANF slightly reduces mean arterial pressure, its vascular effect may not be considered the major event. In addition, increased excretion of bicarbonate and calcium, and the fact that ANF vascular effect is short in time suggest that the peptide may have a non-vascular effect on the processes of bile formation and its modifications along the bile ducts. This extravascular effect may be exerted on the hepatocyte ions exchangers and/or at the ductal level on the processes of excretion and reabsorption of electrolytes and water. PMID- 8441825 TI - Evaluation of the carcinogenic potential of pesticides. 4. Chloroalkylthiodicarboximide compounds with fungicidal activity. AB - The Health Effects Division of the Office of Pesticide Programs (OPP) assessed the carcinogenic potential of three structurally related chloroalkylthiodicarboximide fungicides using a consensus peer review process and EPA's 1986 guidelines for cancer risk assessment. All of the fungicides were categorized as Group B2 (probable human) carcinogens based upon findings of an increased incidence of malignant tumors, or combined malignant and benign tumors, in multiple experiments involving different strains of mice and rats. The primary sites of tumor formation with the chloroalkylthiodicarboximide fungicides in male and/or female mice (CD-1 and B6C3F1) were the gastrointestinal tract (captan, folpet, and captafol), the lymph system (folpet and captafol), and the vascular system (captafol). The main sites of tumor formation in rats of one or both sexes (CR CD, Wistar, or F344 strains) were the kidney (Captan and captafol), uterus (captan), mammary gland and liver (captafol). In addition, positive trends for thyroid, testicular, mammary gland, and lymph node tumors were observed with folpet in the same strains of rats. All three of the compounds exhibited positive mutagenic activity in a variety of in vitro short-term tests for gene mutation, DNA repair, and chromosomal aberrations in prokaryotic and eukaryotic cells, but were not genotoxic in available studies performed under in vivo conditions. The assessment of human cancer risk for captan, folpet, and captafol was made using low-dose extrapolation models. PMID- 8441826 TI - Silicon and silicone: theoretical and clinical implications of breast implants. AB - In the past 10 years, there have been multiple published reports associating silicone breast implants with scleroderma, morphea, SLE, rheumatoid arthritis, CREST syndrome and "human adjuvant disease." The alleged offending material, silicone, is a synthetic polymer containing a silicon-oxygen backbone. Beginning with the heating of SiO2 in the presence of carbon, elemental silicon is produced. Methylchloride is added and the resulting product is hydrolyzed to form low molecular weight prepolymers which are linked to form linear silicone polymers and cross-linked to yield silicone rubbers or elastomers. The polymeric and hydrophobic characteristics of silicone and the presence of electrostatic charges and organic sidegroups make silicone a potentially ideal immunogen, leading to cross-reactivity with autoantigens. Silicon is an essential constituent of proteoglycans which theoretically could result in immunological cross-reactions between silicone and connective tissues. Although the literature contains numerous examples of silicone-associated autoimmune disease, there is no consistent pattern of immunological abnormalities observed. There are, however, some intriguing and interesting observations. Further large-scale studies are needed to determine if a link between silicone exposure and autoimmunity exists. Also, since the inducing events of autoimmune diseases are unknown, studies on silicone could provide a model for autoimmune diseases associated with toxicological factors. PMID- 8441827 TI - Update on artificial sweeteners and bladder cancer. AB - Review of the most recent epidemiologic studies indicates there is no detectable association between artificial sweetener consumption and bladder cancer. The summary relative risk from a meta-analysis of all case-control studies approaches unity (RR .97). This analysis, in combination with new evidence for a unique mechanism of saccharin carcinogenicity in the male rat, leads to the conclusion that saccharin is not related to bladder cancer in humans. PMID- 8441828 TI - Lack of total independence of uncertainty factors (UFs): implications for the size of the total uncertainty factor. AB - This paper assesses the fundamental assumption that multiple uncertainty factors (UFs) are independent of each other and therefore may be combined through a multiplicative scheme. It is argued that a lack of independence is seen in several cases such as that between the interindividual and less-than-lifetime UFs with respect to an age component and results in an error in double counting of UFs. The paper proposes revised UF values based on the concept of the relationship of independent and interdependent UFs. This uncertainty factor revision is then applied to a large number of contaminants for which EPA either has or has proposed MCLs or DWELs. PMID- 8441829 TI - Health and chemical environment in Czecho-Slovakia, international cooperation context. AB - This review provides a record of the present situation with regard to public health and environmental degradation and its underlying causes in Czecho Slovakia, taking into account "ways of life," which is a synonym for its two components: environment and behavior. It gives attention to the priorities which include air and water pollution and food contamination. "Environmental protection" includes the human health protection from air, water, land, and groundwater pollution, ecological protection and natural resource preservation, use of pesticides, food and consumer product safety, and safety associated with the introduction of new chemicals into commerce. Further, this review focuses on the fundamental building blocks for a new environmental policy and management system (Constitution Act, 1991; Environmental Law, 1991; Chemical Act, in preparation; standards regarding chemicals, etc.). With regard to the international concern about the dangers of chemicals for humanity and the natural environment, attention is drawn to the collaboration of Czecho-Slovakia in chemical safety with WHO, IRPTC, and OECD. An important task is to determine what scientific research is needed and to educate administrators, politicians, and the general public in chemical safety. PMID- 8441830 TI - Carbon monoxide and cardiovascular disease: an analysis of the weight of evidence. AB - The role, if any, of environmental tobacco smoke (ETS) in the causation and/or exacerbation of cardiovascular disease remains to be proven and defined. Earlier workers suggested that ETS-associated carbon monoxide, nicotine, and/or polyaromatic hydrocarbons may be causative factors. The purpose of this review was to assess the weight of evidence supporting a role for ambient carbon monoxide in the etiology of human ischemic cardiovascular disease. The findings show that there is scant clinical or experimental evidence to support a role for carbon monoxide in the causation of ischemic heart disease. Further, the results of field studies of relative air quality in nonsmoking and smoking homes, offices, and public places show that ETS contributes only minor and toxicologically insignificant increments in ambient carbon monoxide concentrations. These increments are variable and easily masked by other common carbon monoxide sources such as internal combustion engines and the burning of cooking and heating fuels. It is concluded that if ETS plays a role in the etiology of cardiovascular disease, it is most likely not mediated through carbon monoxide. PMID- 8441831 TI - The concept of multispecies testing in industrial toxicology. AB - The multispecies approach in toxicity testing was originally motivated by the frequent findings of species differences in responsiveness to the pharmacological and acute toxic effects of chemicals. When the guidelines for repeated-dose toxicity experiments were developed in the early 1940s, the concept of using several species of animals was automatically included without careful scientific validation. In response to demands from the U.S. Food and Drug Administration and other national and international regulatory bodies, the protocols for acute and repeated-dose toxicity testing became highly formalized, and the requirement to conduct all studies in a rodent and a nonrodent species was established. With time, most guidelines also specified the species that had to be used, and the most common recommendation was to use the rat as the rodent and the dog as the nonrodent. In recent years, many reasons for differences in responsiveness of various animal species and man to the toxic effects of chemicals have been identified. This knowledge is now used extensively to assess contradictory findings in routine safety studies in the rodent and the nonrodent species. It is often possible to identify the species that appears to be more predictive for man than the other, and risk assessment for man is then based mainly on the findings in the more representative species. Since contrary toxicological findings in rodents and nonrodents occur frequently, one could propose to perform detailed scientific investigations prior to the selection of the species for toxicological investigations, as it has already been suggested by the working group of the European Society for the Study of Drug Toxicology in 1965 and is still an option mentioned in the currently valid EEC drug safety guidelines of 1983. For practical reasons such early investigations of biological properties and pharmacokinetic and metabolic characteristics of test chemicals in various laboratory animal species are hardly ever done prior to the initiation of safety studies. However, techniques are now developed with which species selection for toxicity testing can be made on the basis of rational scientific investigations. PMID- 8441832 TI - Amelioration of glycerol-induced acute renal failure in rats by an adenosine A1 receptor antagonist (FR-113453). AB - A potent adenosine A1 receptor antagonist, FR-113453, was tested for its preventive effect on glycerol-induced acute renal failure in rats. First, the optimum timing of FR-113453 administration was studied. Oral FR-113453 (100 mg/kg) given 1 h before or 5-10 min after glycerol injection produced a significant reduction of the serum creatinine at 24 h (4.3 +/- 0.8 mg/dL [vehicle] vs. 1.4 +/- 0.4 mg/dL [FR-113453], and 4.7 +/- 1.1 mg/dL vs. 1.3 +/- 0.6 mg/dL, respectively, p < 0.001). However, when FR-113453 was given 2 h after glycerol injection, the serum creatinine did not improve. Creatinine clearance at 24 h after the induction of acute renal failure was significantly better in rats given FR-113453 (100 mg/kg) 1 h before glycerol than in rats given vehicle alone (0.08 +/- 0.08 mL/min vs. 0.01 +/- 0.02 mL/min), (p < 0.01). The kidney weight was lower and less severe histologic changes were observed at 24 h in the FR 113453-treated group. Renal blood flow (measured using 85Sr microspheres) did not change at 24 h after glycerol injection (3.0 +/- 0.9 mL/min/g [vehicle] vs. 3.6 +/- 0.9 mL/min/g [FR-113453]), but renal vascular resistance was significantly reduced by FR-113453 (47.9 +/- 37.9 vs. 26.4 +/- 5.2 mm Hg/mL/min/g, p < 0.05). Beta-ATP levels (measured by 31P-magnetic resonance spectroscopy) were reduced in glycerol-induced acute renal failure, with no difference between the vehicle and FR-113453-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441833 TI - Renal microcirculation in experimental acute pancreatitis of dogs. AB - In order to understand the mechanism of acute renal failure frequently observed in severe acute pancreatitis, renal microcirculation and renal hemodynamics were investigated during experimental acute pancreatitis in dogs induced by autologous bile and trypsin mixture into the pancreatic duct. Renal tissue blood flow (hydrogen gas clearance method), renal arterial blood flow, and cardiac output (transonic blood flow meter) were each measured for 5 h after induction of pancreatitis. The effect on renal hemodynamics of a new synthesized protease inhibitor--E-3123; 4-(2-succinimidoethylthio)phenyl-4-quanidinobenzoate methane sulfonate--intravenously infused at the rate of 3 mg/kg/h was also investigated. The mean blood pressure and pulse pressure decreased after induction of pancreatitis. Renal microcirculation and renal artery blood flow decreased during the experiment. However, in dogs with treated by E-3123, renal microcirculation was preserved during the first hour of the experiment and decreased gradually afterward, but it was significantly higher than that of the dogs without E-3123 during 3-5 h. The mean blood pressure and pulse pressure were preserved nearly at preoperative levels during the experimental period. We concluded that renal microcirculation decreased concomitantly with a deterioration of acute pancreatitis, and that the new pancreatic protease inhibitor E-3123 may have some beneficial effect to improve renal hemodynamics in the early period of acute pancreatitis. PMID- 8441834 TI - Renal lymphatic obstruction in diabetic rats induces systemic hypotension. AB - We obstructed renal lymph drainage from a single kidney in diabetic rats who had received 65 mg/kg streptozotocin 6 months prior to the study. Lymphatic obstruction led to a progressive fall in systematic blood pressure from a mean arterial pressure of 101 +/- 5 (SEM) mm Hg (n = 7) to 62 +/- 4 mm Hg (n = 5) (p < .02) after 1.5 h. No change was seen in a sham-operated animal. Despite the decline in systemic blood pressure there was no significant change in the GFR of either kidney. Sodium excretion increased significantly in the experimental kidney. There was no change in the urinary excretion of cyclic GMP from either kidney, and plasma levels of atrial natriuretic peptide (ANP) did not change (55 +/- 21 pg/mL pre- to 64 +/- 18 postobstruction). The results are consistent with a systemic vasodilatation after lymphatic obstruction. The mechanism of this response is still under investigation, but apparently it does not involve ANP. PMID- 8441836 TI - Thyroid hormone levels in acute renal failure. AB - We investigated the plasma concentrations of thyroid hormones in 27 patients with acute renal failure. Both the mean free T3, 1.17 +/- 0.74(SD) pmol/L (range 0.5 2.9 pmol/L) and total T3 plasma concentrations, 0.43 +/- 0.14 nmol/L (range 0.3 0.7 nmol/L) were reduced compared to the normal range (3.3-8.2 pmol/L and 1.0-3.0 nmol/L, respectively). In all 15 patients with plasma creatinine > 3.33 mg/dL (295 mumol/L), the mean FT3 was 0.92 pmol/L and the plasma concentrations have all been < 1.5 pmol/L. There was a weak correlation between the plasma creatinine and the plasma concentrations of TT3 (r = 0.38, p = 0.049). Similarly, both plasma free T4 and total T4 were also reduced in the patients compared to the normal range: mean free T4 5.91 +/- 3.68 pmol/L, range 1.0-13.1 pmol/L, and total T4 47.80 +/- 29.31 nmol/L, range 5-99 nmol/L; normal range 9.4-25.0 pmol/L and 50 160 nmol/L, respectively. There was no difference between the ranges in either plasma TSH, patients 1.19 +/- 1.25 mU/L, range 0.1-4.9 mU/L, vs. control range 0.3-6.0 mU/L; and TBG, patients 19.05 mg/L +/- 3.69, range 11.0-26.9 mg/L, controls range 13.0-30.0 mg/L. Thus we have determined that patients in the early phase of ARF have consistently reduced plasma concentrations of both free and total T3, and reduced concentrations of free and total T4; and that the reduction of TT3 is dependent upon the plasma creatinine level. PMID- 8441835 TI - Effect of oxypurinol on renal reperfusion injury in the rat. AB - Oxygen-based free radicals produced by the enzyme xanthine oxidase may be involved in postischemic reperfusion injury. To determine whether oxypurinol, a xanthine oxidase inhibitor and the major metabolite of allopurinol, attenuates renal ischemic reperfusion injury, and, if so, to determine its most effective dose, oxypurinol 2.5, 5, 10 or 20 mg/kg BW was infused 20 min prior to 20 min of complete renal ischemia in uniephrectomized rats. Animals treated with 5 mg/kg BW oxypurinol had significantly higher creatinine clearances on the first and second days postischemia than did untreated animals. In other animals given either buffered saline or oxypurinol at 5 mg/kg BW i.v. 20 min before ischemia, the inulin clearance (CIn) returned to near-control values within 1 h after ischemia. At 24 h there was a secondary decline in the CIn in animals receiving buffered saline, whereas in the animals treated with oxypurinol, this decline was less evident. In animals given oxypurinol at 5 mg/kg BW 40 min after ischemia, the CIn was significantly greater than in those receiving buffered saline. No changes in renal blood flow or renal vascular resistance were observed, suggesting that the effect of oxypurinol was not hemodynamically mediated. Analysis of plasma hypoxanthine, xanthine, uric acid and oxypurinol levels by high-pressure liquid chromatography revealed that in the absence of oxypurinol, a significant increase in uric acid production occurred between 20 and 170 min after the period of ischemia. In the presence of oxypurinol, there was a marked reduction in the rate of production of uric acid for the first 3 h postischemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441837 TI - The bimodal mortality pattern of acute renal failure in children. AB - A total of 1784 children suffering from acute nonobstructive anuric renal failure requiring dialysis were studied in the Pediatrics Nephrology unit of Institute of Postgraduate Medicine and Research, Dhaka, Bangladesh, for the 10-year period 1981-1990. The patients were divided into two groups: Group I, the majority of the children (94.5%), presented with acute renal failure without evidence of hemolysis and were labeled as acute ischemic renal failure (AIRF), and the remaining 5.5% of the children with acute renal failure (ARF) showing features of severe hemolysis were labeled as hemolytic uremic syndrome (Group II.) The children of group I had mean age 4 (0.5-10) years, mean period of anuria 5 (2-13) days, and had mean serum creatinine 701 +/- 267.98 mumol/L. The overall mortality in this group was 89%. Children in Group II had mean age 2 (0.2-6) years, mean duration of anuria 3 (2-5) days, and mean serum creatinine level 500 +/- 100 mumol/L. The mortality rate in this group was 15%. In spite of some differences between the two groups the difference in the mortality rate between the two groups was significant (p < 0.001). It is concluded that AIRF in children bears a much poorer prognosis compared to that of ARF due to HUS. PMID- 8441838 TI - Dopamine and renal blood flow in radiocontrast-induced nephropathy in humans. AB - Previous studies suggest a role for renal vasoconstriction in the pathogenesis of radiocontrast-induced nephropathy (RCIN). A renal vasodilator such as dopamine may be protective. However, the effect of dopamine on renal blood flow (RBF) in patients with chronic renal failure (CRF) is controversial. Patients with CRF of diabetic (DM) or nondiabetic (NDM) origin were hydrated with 0.45% NaCl intravenously at 100 mL/h for 12 h and then randomized to either 0.45% NaCl IV at 100 mL/h (Group 1) or dopamine IV at 2 micrograms/kg/min in 0.45% NaCl at 100 mL/h for 2 h during and after cardiac catheterization. Mean arterial pressure (MAP), cardiac output (CO), and RBF were measured at baseline (t = 0), after 5 min of vehicle (Group 1) or dopamine (Group 2) but before ionic radiocontrast (t = 5 min), after ventriculogram (t = 15 min), and after coronary angiography (t = 65 min). Serum creatinine (SCr) was measured at baseline and 24 and 48 h after cardiac catheterization. RCIN was defined as a 25% increase of SCr above baseline 48 h after cardiac catheterization. Baseline characteristics demonstrated the groups to be equivalent in age, SCr, creatinine clearance, CO, MAP, RBF, and radiocontrast dose administered. The incidence of RCIN was not different between Group 1 and Group 2 (Group 1, 6 of 15 patients; Group 2, 5 of 15 patients). Dopamine infusion was associated with a significant increase in RBF at 5 min (Group 1, 110 +/- 13%; Group 2, 193 +/- 40% at t = 5, p < .05). RBF remained elevated throughout the catheterization in Group 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441839 TI - Acute renal failure in patients with drug-induced acute interstitial nephritis. AB - The clinical features, laboratory evaluation, and outcome were analyzed in 23 patients with acute renal failure (ARF) and drug-induced acute interstitial nephritis (21 proven with biopsy). The groups of drugs implicated were: antibiotics (20 cases), nonsteroidal anti-inflammatory drugs (2 cases), and other drugs (phenobarbitone, 1 case). The clinical and laboratory signs of the disease appeared 3 to 28 days after exposure to the drug. Fever, skin rash, and flank tenderness were the most common clinical features observed (87%); and hematuria (100%), sterile pyuria (83%), and eosinophilia (39%) were established by laboratory tests. Hemodialysis (HD) was performed in 7 patients. Complete normalization of kidney function was observed in 3 patients; improvement to basal level in 3 patients (this group had preexisting renal disease); and CRF, requiring HD, in 1 patient. Renal function improved in all patients with mild to moderate renal insufficiency regardless of the therapy involved. Statistical evaluation could not confirm any significant differences between status of renal function at presentation, treatment (corticosteroids versus symptomatic and supportive measures only), and outcome of drug-induced acute interstitial nephritis (AIN). In summary, ARF due to drug-induced AIN has a favorable course with good prognosis regardless of the use or nonuse of corticosteroids in management strategy. PMID- 8441840 TI - Effects of dietary protein on renal ischemia induced tubular necrosis. AB - Previously we have shown that the amount of protein in a dietary regimen prior to the induction of renal ischemia will significantly affect the degree of postischemic acute renal failure (Andrews PM, Bates SB: Kidney Int 30:299-303, 1986). The present investigation was undertaken to determine what effect dietary protein regimen has on the histopathology of renal ischemia. Rats were pair-fed for 2 weeks on either 0% or 5% (restricted), 20% (normal), or 60% (high) purified protein isocaloric diets. Ischemia was induced by 45 min of renal pedicle clamping. Light and electron microscopic evaluation of kidney morphology immediately following renal ischemia (prior to blood reflow) revealed that the extent of morphological damage to cells lining proximal convoluted tubules and the thick ascending segments of Henle's loop increased with increasing concentration of dietary protein. However, all dietary protein groups also exhibited heterogeneity in the extent of damage to different nephrons within the same kidney. PMID- 8441841 TI - Should glucose be administered before, with, or after insulin, in the management of hyperkalemia? AB - To assess the hypokalemic effect of intravenous glucose (25 g i.v. in 5 min) followed by regular insulin (10 U) bolus, as well as the incidence of hypoglycemia, a well-known side effect of this intervention, nine uremic patients on maintenance hemodialysis were studied. Measurements were done of plasma potassium, glucose, insulin, and C-peptide before, and 15, 30, 45, and 60 min after glucose and insulin. The intervention induced a significant fall in plasma potassium level, a significant rise and then fall in plasma glucose, and a significant increase in the insulin and C-peptide levels. These data suggest that hypertonic glucose infusion should precede, not follow, the insulin bolus in the management of hyperkalemia. Such an approach is clinically effective and well tolerated, with no hypoglycemic side effects. PMID- 8441842 TI - Acute renal failure at the Lagos University Teaching Hospital: a 10-year review. AB - The Dialysis Centre at the Lagos University Teaching Hospital was established in November 1981 as the first unit in West Africa to undertake chronic hemodialysis treatment. More than 500 patients have been managed in the center since then. Of these, 175 were cases of acute renal failure. The causes and outcome of these cases have been reviewed. There were 89 males (50.9%) and 86 females (49.1%). The majority, 111 (63.4%), were aged < 40 years. The main cause was sepsis, which occurred in 67 cases (38.3%). Gynecological and obstetric cases were 45 (25.7%), including 14 cases (8%) of pregnancy toxemia. Other causes were hemorrhage 18 (10.3%), obstructive uropathy 6 (3.4%), acute glomerulonephritis 8 (4.6%), and poisoning with "Holy Water" 6 (3.4%) and other nephrotoxins 9 (5.1%). Sixty-nine patients (39.4%) died in hospital, 92 (52.6%) recovered, and the fate of 14 (8%) was unknown as they were transferred from the hospital. Reasons for the high mortality included delayed hospitalization, selection of severe cases, and inability of patients to afford more than only one session of dialysis even though they needed more. It is hoped that as awareness of the value of dialysis increases and early treatment can be sought, the overall mortality will be reduced. PMID- 8441843 TI - Effect of calcium antagonist on renal graft function. AB - Studies in experimental models of renal ischemia have shown that calcium antagonists are effective in the protection from the ischemic insult. Thirty-five patients who received a kidney graft over a 2-year period (nifedipine group) were compared with 35 consecutive transplanted patients (control group). The two groups were compatible with regard to age, sex, duration of hemodialysis, graft matching, and total number of blood transfusions. The patients in the nifedipine group were given 0.2 mg nifedipine (10% solution) through the renal artery immediately after revascularization, and also nifedipine per os during all the study periods. Adequate diuresis (1 mL/min) was obtained in 14.5 +/- 37.2 and 43.9 +/- 46.8 h after transplantation in the nifedipine and control groups respectively (p < 0.01). The frequency of acute tubular dysfunction and the mean serum creatinine concentrations were found to be higher in the control group. Fractional excretion of sodium was not found to be different in the two groups on the first day, but it was significantly lower by the first week after transplantation in the nifedipine group (p < 0.05). Acute rejection episodes were found to be more frequent in the control group during the first 6 months after transplantation (p < 0.05). It is suggested that nifedipine is effective in the protection of renal function after transplantation. PMID- 8441844 TI - Acute renal failure due to tubular necrosis caused by wildfowl-mediated hemlock poisoning. AB - We report the clinical and histological findings in patients with acute renal failure caused by the ingestion of wildfowl who had eaten hemlock buds. Neurotoxic effects were accompanied by rhabdomyolysis, myoglobinuria, and acute tubular necrosis. Histological studies showed diffuse degeneration of the tubular epithelium. Immunohistological studies demonstrated the presence of myoglobin and actin in renal tubular cells. PMID- 8441845 TI - Anti-mullerian hormone: the Jost factor. PMID- 8441846 TI - The growth hormone/prolactin receptor family. PMID- 8441847 TI - Molecular genetics of Laron-type GH insensitivity syndrome. PMID- 8441848 TI - Conventional and nonconventional uses of growth hormone. AB - Although GH has been available as a therapeutic agent for the GH-deficient child for more than 30 years, the conditions of its use have yet to be optimized. The availability of biosynthetic material has provided researchers with the opportunity to develop the protocols necessary to begin to finally answer the most fundamental questions pertaining to dose, frequency, and duration of treatment. It has also permitted the initiation of prospective trials in a large number of conditions that result in childhood short stature, with the expectation that some or many of them will be treated effectively and safely. Finally, it has opened the door to an entire spectrum of potentially new uses of GH and other growth factors for so-called nonconventional indications. That these have implications that range from the short-term rapid healing of a burn graft site, to the more efficient induction of ovulation, to the long-term preservation of lean body mass has excited the interest of investigators in many fields of medicine and physiology. Thus, the recent progress reported in this paper is really the beginning of the new research that will take place with GH and growth factors. PMID- 8441849 TI - Site-directed mutagenesis in the mouse. PMID- 8441850 TI - The molecular basis for growth hormone-receptor interactions. AB - High-resolution mutational and structural analyses of purified components have revealed a great deal about the molecular basis for growth hormone action. The structural and functional aspects of the interactions between hGH and its receptors have been largely elaborated. From these studies it has been possible to engineer homologues of hGH to bind to the hGH receptor and act as potential antagonists. Receptor-selective and high-affinity analogs have also been constructed based on a combination of alanine scanning and monovalent phage display. From this molecular work much has been revealed about the biology of hGH (Fig.9). Our data suggest that hGH is stored in the pituitary as a (Zn2+,hGH)2 complex. On release from somatotropic vesicles it dissociates into a monomeric form and reveals its primary receptor binding site (site 1). Free hGH can bind to the hGHbp in serum to form monomeric or dimeric complexes that slow the clearance of hGH (Moore et al., 1989). However, because the affinity for the full-length receptor is greater, hGH can bind to it preferentially. Furthermore, the constitutive levels of the hGHbp (approximately 0.5 to 1 nM) (Baumann et al., 1986; Herrington et al., 1986) are considerably below the levels of hGH after pulsatile release (approximately 2 to 5 nM) (Thompson et al., 1972). Our data indicate that hGH binds to the hGH receptor on cell membranes through site 1 and subsequently forms dimers through site 2. We believe a similar process may occur for hGH to activate the hPRL receptor, except that Zn2+ is required for site 1 association. Such receptor dimers are then activated and capable of interacting with other cellular components that may mediate the hGH "signal." Recently, based upon this proposed mechanism, we produced potent antagonists to the hGH receptor (Fuh et al., 1992) and hPRL receptor (G. Fuh, P. Colosi, W. Wood, and J. Wells, unpublished results). These antagonists bind tightly to site 1 but are blocked in their ability to bind site 2 and dimerize the receptor. We believe these methods and discoveries will be relevant to the study of signaling by other hematopoietic hormones and receptors as well as other hormones and receptors. PMID- 8441851 TI - Catecholamine receptors: structure, function, and regulation. PMID- 8441852 TI - Thyroid hormone regulation of thyrotropin gene expression. AB - Thyroid hormones suppress the synthesis and release of thyrotropin from thyrotropes in the anterior pituitary gland, a feature that is critical in the classic negative-feedback loop of the pituitary-thyroid endocrine axis. The major effect of thyroid hormones in this system is exerted at the transcriptional level. The molecular mechanisms by which there is negative regulation of TSH subunit gene expression by thyroid hormone have been elucidated. The TSH subunit genes have isolated and characterized. Structure-function analyses using fusion genes and DNA transfection approaches have defined the putative negative TREs among the promoters of the rat, mouse, and human alpha and TSH beta genes. These sequences are either largely overlapping direct TRE half-sites, TRE half-sites as direct repeats gapped by two nucleotides, or single TRE half-sites. These arrangements are distinct from those seen in positive TREs. Recent knowledge regarding the molecular mechanisms of thyroid action in general forces consideration of multiple TR isoforms, TR heterodimer partners (TRAPs), and thyroid hormones in the ultimate mechanisms of negative action. Several models have been proposed, but none has yet been proved. In addition, the role of thyroid hormone in the regulation of gene expression at the posttranscriptional level is beginning to be addressed. Future work should continue to illuminate these important facets of gene regulation. PMID- 8441853 TI - Prohormone structure governs proteolytic processing and sorting in the Golgi complex. PMID- 8441854 TI - Endocrinology alfresco: psychoendocrine studies of wild baboons. PMID- 8441855 TI - Heterogeneous secretory response of parathyroid cells. PMID- 8441856 TI - Progesterone inhibits estrogen-induced increases in c-fos mRNA levels in the uterus. PMID- 8441857 TI - Genotoxic damage and aberrant proliferation in mouse mammary epithelial cells. PMID- 8441858 TI - LHRH- and (hydroxyproline9) LHRH-stimulated hCG secretion from perifused first trimester placental cells. PMID- 8441859 TI - Tyrphostins inhibit Sertoli cell-secreted growth factor stimulation of A431 cell growth. PMID- 8441860 TI - Induction of calcium transport into cultured rat Sertoli cells and liposomes by follicle-stimulating hormone. PMID- 8441861 TI - Pituitary in vitro LH and FSH secretion after administration of the antiprogesterone RU486 in vivo. PMID- 8441862 TI - Release of immunoreactive inhibin from perifused rat ovaries: effects of forskolin and gonadotropins during the estrous cycle. PMID- 8441863 TI - Identification and partial purification of a germ cell factor that stimulates transferrin secretion by Sertoli cells. PMID- 8441864 TI - Expression of the FSH receptor in the testis. AB - FSH has multiple and changing roles in the regulation of spermatogenesis. The first function of FSH is to increase the number of Sertoli cells by stimulation of their mitotic activity. During the prepubertal phase of development, FSH is important for the maturation of the Sertoli cells. Hormonal stimulation of tight junction formation and specific protein secretion are essential. In the adult rat, some of the functions carried out by FSH in prepubertal animals are assumed by testosterone. However, there is evidence that even in the adult rat, FSH is important for quantitatively normal spermatogenesis. The gene for the FSH receptor is large (greater than 85 kb) and complex (10 introns) and is structurally similar to the genes for the LH and TSH receptor. The promoter region of the FSHR gene has been identified and is active in the expression of transgenes in transfected Sertoli cells. We have shown that the FSH receptor mRNA is present in the testes of the adult rat and that the levels of this mRNA are changing during the cycle of the seminiferous epithelium. The presence of relatively high levels of FSHR mRNA in stages XIV-II of the cycle and the relatively low levels in stages VII-VIII suggest that the FSH receptor is carefully regulated in adult rats and presumably has an important function in spermatogenesis. The levels of FSHR mRNA in cultured Sertoli cells are immediately reduced in the presence of FSH or phorbol esters, but the levels soon return to normal. PMID- 8441865 TI - Differential gene expression from a single transcription unit during spermatogenesis. PMID- 8441866 TI - Stewart's quantitative acid-base chemistry: applications in biology and medicine. AB - We review P.A. Stewart's quantitative approach to acid-base chemistry, starting with its historical context. We outline its implications for cellular and membrane processes in acid-base physiology; discuss its contributions to the understanding and analysis of acid-base phenomena; show how it can be applied in clinical problems; and propose a classification of clinical acid-base disturbances based on this general approach. PMID- 8441867 TI - Effect of extracellular fluid volume expansion on avian lung fluid balance. AB - We examined the effects of acute expansion of extracellular fluid volume (ECFV) on lung fluid balance and the ultrastructure of the pulmonary air-blood barrier in chickens (Gallus domesticus). We compared changes in extravascular lung water content (EVLW) to the sum of mean pulmonary capillary blood pressure and plasma protein osmotic pressure (tau c), as a measure of net intravascular filtration pressure (NIFP), produced by graded infusion of avian Ringer's solution. NIFP increased with each volume load largely as a result of decreased tau c resulting in progressive increase in EVLW. Progressive interstitial edema occurred with fluid accumulation restricted to the inter air capillary septa, sparing the gas exchanging regions of the air-blood barrier. This was associated with increased thickness of the septa and increased pulmonary capillary endothelial vesiculation. The effect of increased ECFV on pulmonary hemodynamics and lung fluid balance in Gallus is similar to that in mammals. PMID- 8441868 TI - Diffusion limitation in comparative models of gas exchange. AB - Piiper and Scheid (Resp. Physiol. 23: 209-221, 1975) compared different models of external gas exchange with performance indices defined as functions of ventilatory/perfusive and diffusive/perfusive conductance ratios (Gvent/Gperf and Gdiff/Gperf, where Gdiff is diffusing capacity). We expanded their analysis to include: (1) delta pD, the average partial pressure gradient driving diffusion across the exchange barrier, normalized to the maximum gradient available (Pi Pv), and (2) Jdiff, the sensitivity of total conductance to changes in Gdiff, where total conductance is the ratio of gas flux to the maximum gradient [GTOT = M/(Pi-Pv)]. Although the counter-current model is most efficient, it is more sensitive than cross-current or ventilated pool models to changes in Gdiff. For given Gvent, Gperf and Pi-Pv, maximum GTOT may not be achieved in the counter current model until Gdiff is over ten-fold greater than that necessary for maximum GTOT in the other models. Experimental data also shows greater Jdiff and diffusion limitation in fish than in birds or mammals. We conclude that counter current O2 exchange cannot approach ideal levels as closely as the ventilated pool or cross-current models in nature. PMID- 8441869 TI - Respiratory exchanges in the incubated egg of the domestic guinea fowl. AB - The daily O2 uptake (MO2) and CO2 production (MCO2) rates were measured in guinea fowl eggs with a wide range of mass specific shell water vapor conductance, spGH2O [0.108 to 0.365 mg.(g.Torr.day)-1], from day 10 to the end of incubation, day 28. The respiration rate showed a plateau, from day 22 to day 24, typical of a precocial bird: MO2 approximately 21.4 and MCO2 approximately 15.2 mmol.day-1. The plateau MO2 value was that predicted by allometric relation. At the plateau, respiratory exchanges appeared significantly limited by spGH2O. The limiting effect of spGH2O on respiratory metabolism began as soon as day 18 (64% of incubation time). The respiratory ratio was 0.75 at day 10, decreased to 0.65 0.66 on days 12-14 and stabilized at 0.70-0.71 on days 20-28. PMID- 8441870 TI - Gas exchange dynamics with sinusoidal work in young and elderly women. AB - The objective of this study was to model the dynamics of, and interrelationships among, gas exchange, ventilation, and heart rate responses to sinusoidal forcing in young and elderly women. Nineteen females, 22-28 years (n = 10) and 62-73 years (n = 9) volunteered for the study. All experiments were conducted at work rates below the ventilatory threshold (TVE). A sine wave test consisted of 4 min of cycling (60 rpm) at a work rate equal to the mean of the limits of sinusoid (60% TVE) followed by 16-20 min of a sinusoidally varying work rate (30-90% of TVE) and ending with 4 min of cycling at 60% TVE. The periods were 0.75, 1.0, 1.5, 3.0, 6.0, 10.0 min, assigned randomly. The averaged data were used to determine amplitude and phase lag of the sinusoidal response of VO2, VCO2, VE, fH, PETCO2, and PETO2. Bode plots demonstrated that the dynamics of the cardiorespiratory responses were all well-described by a first-order exponential equation with a delay for both young and elderly subjects. The time constants were much longer in the elderly. Nevertheless, there appeared to be a strong link between the relative slowing of the four components of the gas transport system (VO2, VCO2, VE, and fH). This may suggest one single factor is reflected in the slowing of all components in older subjects. PMID- 8441871 TI - Serotonin is necessary for short-term modulation of the exercise ventilatory response. AB - The exercise ventilatory response is augmented during conditions of increased respiratory dead space (delta Vd), a phenomenon that we refer to as short term modulation (STM). To test the hypothesis that serotonin is necessary in the mechanism underlying STM, experiments were conducted on ten awake goats. Ventilation, CO2 production and PaCO2 were measured at rest and during treadmill exercise (4 km/h, 5% grade), with and without delta Vd (0.25 L), before and after systemic administration of the serotonin receptor antagonist, methysergide maleate (n = 6; 1 mg/kg, i.v.), or the tryptophan hydroxylase inhibitor, p chlorophenylalanine (PCPA; n = 4; 100 mg/kg, i.v.). Pre-methysergide: (1) PaCO2 decreased from rest to exercise to a similar degree with (-1.9 mmHg) and without (-1.8 mmHg) delta Vd; (2) the exercise ventilatory response increased 59% +/- 13% (P < 0.01) with delta Vd, accounting for similar exercise PaCO2 regulation and demonstrating STM; and (3) effects of delta Vd on exercise tidal volume and frequency responses were inconsistent. Post-methysergide: (1) there were no significant effects on ventilation or PaCO2 at rest or during exercise in control (mask) conditions; (2) the exercise ventilatory response was unaffected by delta Vd, thereby allowing PaCO2 to increase 4.1 +/- 3.0 mmHg from rest to exercise (P < 0.05); and (3) with delta Vd during exercise, the tidal volume response was increased, but was offset by a decreased frequency response. Following PCPA (16 24 h): (1) hyperventilation was evident at rest and during exercise; (2) the exercise ventilatory response was augmented, indicating STM; and (3) the exercise ventilatory response with delta Vd was not affected further, allowing PaCO2 to increase from rest to exercise and indicating an inability to elicit further STM. These data suggest that serotonin is necessary for short term modulation of the exercise ventilatory response with increased respiratory dead space, although the location of relevant serotonin receptors is not yet clear. PMID- 8441872 TI - Respiratory responses to progressive ambient hypoxia in the sturgeon, Acipenser baeri. AB - Changes in respiratory and acid-base variables were studied in siberian sturgeon, Acipenser baeri, during progressive deep hypoxia followed by recovery under normoxic conditions. During hypoxia, both ventilatory frequency and amplitude increased and this sturgeon was able to maintain standard oxygen consumption down to a low critical level of ambient PO2 (PWO2 < 40 mmHg). During the posthypoxic period, an O2 debt was repaid by an elevated oxygen consumption (nearly double control value at 1 h), indicating that a shift to anaerobic metabolism had occurred during exposure to severe hypoxia. Gradually increasing ambient hypoxia initially induced a respiratory alkalosis. Below the critical PWO2 level and during normoxic recovery, a sudden flush of lactate into the blood was associated with a typical metabolic acidosis which was almost totally compensated 3.5 h after return to normoxia. Thus, as for most other fish, respiratory responses of the sturgeon to progressive hypoxia reveal a typical O2 regulatory behavior. PMID- 8441873 TI - Cardiac output but not high pulmonary artery pressure varies with FIO2 in exercising horses. AB - Horses have high mean pulmonary artery pressure (Ppa) both at rest and during exercise (approximately 30 and > or = 80 mmHg, respectively). The mechanisms are unknown. To see if hypoxic pulmonary vasoconstriction (HPV) plays a role, we compared pulmonary artery pressure-flow (Ppa-Q) curves when inspired O2 fraction (FIO2) was 0.16, 0.21, and 0.30, in 5 normal Thoroughbred horses standing quietly and while galloping at 10 and 14 m/sec on a level treadmill. We calculated O2 consumption (VO2) from measurements of respired gas composition and flow, and calculated Q from VO2 and measurements of oxygen content in arterial and mixed venous blood (CaO2 and CVO2). VO2 was 3.8, 74 and 128 ml.min-1.kg-1, at rest and at 10 and 14 m/sec, and did not vary with FIO2 at any speed. At 14 m/sec only, when FIO2 was lowered to 0.16, CaO2 fell (to 14.7 from 20 ml/dl on air), Q increased (to 0.86 from 0.66 L.min-1.kg-1 on air), and stroke volume increased (to 4.1 from 3.2 ml.kg-1 on air). Slopes and intercepts of Ppa-Q curves did not vary with FIO2. We conclude that HPV does not contribute to the high Ppa of exercising horses breathing air near sea level. PMID- 8441874 TI - Blood O2 transport and Hb types in the embryonic Tammar Wallaby (Marsupialia, Macropus eugenii). AB - Blood oxygen transport and hemoglobin type have been studied in the developing Tammar Wallaby from 20 days gestation, just after the circulation first forms, until 28 days gestation, 2 days after birth. The oxygen equilibrium curves (OECs) of the embryonic whole blood had high P50 values, mean being 44.6 mmHg at 36 degrees C, PCO2 = 40 mmHg. In contrast to other viviparous species studied, the embryonic OECs were well to the right of the maternal OEC. There was no significant change in P50 throughout the age range studied. The curves had high Hill coefficients above about 50% saturation (mean = 5.65), indicating cooperativity between hemoglobin tetramers. The Bohr effect (measured as delta log P50/delta log PCO2) was low, about half that of the adult. The early embryos (days 20 and 21) had only 2 or 3 Hb types, with the other embryonic Hbs appearing by 22 days of gestation. The proportion of the four embryonic Hbs changed during development although one type was always predominant (> 45%). This is the first serial study of blood O2 carriage and Hb type in developing marsupial embryos. The finding of a right-shifted embryonic OEC throughout intrauterine development suggests that, contrary to current belief, a right-shifted curve may be physiologically advantageous to a developing embryo. PMID- 8441875 TI - [What is your diagnosis? Pathological fracture in fibrous cortical defect (non ossifying bone fibroma)]. PMID- 8441876 TI - [Infusion therapy with antidepressants in patients with depression]. AB - After a review on the evidence for efficacy of infusions with antidepressants a study is presented which included 100 depressed patients (77 females, 23 males) treated with infusions at a private clinic in Basel. In almost all cases "Ludiomil" and "Anafranil" were administered. Women in the forth decade were the most important age group in the females. Immediately after discharge from the hospital 72.5% of the patients assessed their condition as healthy or markedly improved, 23% as slightly improved, 39% remained well for over 1 year, 14.5% for 7 to 12 months. 26% had previously attempted suicide at least once. Intravenous infusion-therapy with antidepressants has advantages over oral administration of the same substances that are however not solely founded on pharmacologic but also on psychologic reasons. PMID- 8441877 TI - [Iatrogenic methadone poisoning]. AB - Two young drug addicts received in the course of their treatment a 10-fold overdose of methadone by error. One person died, the other was severely intoxicated but survived. The cause for the mistreatment was the unawareness of the medical personnel, that did not realize the change in concentration of the methadone stock solution from 0.1% to 1.0%, provided by the pharmacy. To prevent such mistakes in the future a change in labelling of the bottle giving directions for correct dosing is suggested. PMID- 8441878 TI - [Clinical late results following surgical ablation of an accessory atrioventricular connection in Wolff-Parkinson White syndrome]. AB - All patients operated because of WPW-syndrome between 1980 and 1990 at the University clinics of Zurich were followed up by clinical examination and by electrocardiography. Relief from symptoms (tachycardia, vertigo and/or syncopes) was defined as "symptomatic" success, lack of preexcitation in the ECG at rest as "surgical" success. Overall 56 patients (40 men, 16 women) aged from 13 to 66 years had been operated in the stated time period. Before operation 52 of these patients had pre-excitations in the ECG, 54 had tachycardia and 23 had syncopes. None of the patients died from the operation. In order to localize the AAVVs epicardial cartography was performed in all patients during operation before the AAVVs were cut through an endocardial access. The follow-up was possible after an average interval of 5.5 years (1-120 months) in 50 of the 56 patients. One patient died 10 years after operation from heart failure. 6 patients were reported to be out of the country. The follow-up revealed symptomatic success of the intervention, defined as absence of tachycardia, in 88% (44 out of 50). In 84% (42 out of 50) also a surgical success of the operation was found. In these patients the accessory atrio-ventricular bundle had been successfully ablated, and they were free of tachycardia and of preexcitation in the ECG. Two patients with persisting preexcitation remained free of clinical symptoms. Insofar the rate of symptomatic success was higher than the rate of surgical success. Summarizing the results surgical transsection (ablation) of an accessory atrioventricular bundle in patients with WPW-syndrome is a good therapeutic option with favorable long term success. It has today still its place--in selected cases--as alternative to the now available radio-frequency ablation. PMID- 8441879 TI - [Pneumonia and abdominal mass]. PMID- 8441880 TI - [A case from practice (265). Occlusive hydrocephalus with tumor of uncertain histology--low-grade astrocytoma--ependymoma]. PMID- 8441881 TI - [25 patients undergoing laparoscopy for pelvic pain]. AB - 25 patients have involved in this research, who have chronic gynecologic pelvic pain and each of them had normal gynecologic examination. Chronic pelvic pain has been found mostly between 30-39 years age group married, multipar females, associated with 44% dysmenorrhea, 36 p. cent dyspareunaie. Cultures and clinical examinations were all negative as a sign of infection. Experienced intra abdominal operation or infection were causes of pelvic pain (48%), especially appendectomy has a prominent place (75%). Laparoscopic investigation showed: 16 p. cent adhesions, 28 p. cent chronic annexitis, 16 p. cent experienced pelvic inflammatory disease, 8 p. cent uterine leiomyoma, 4 p. cent each endometriosis, experienced parametritis and haemorrhagic lutein cysts. Instead of making group of lesions, we prefer to describe it, in numbers as infection importance coefficient (IIC), which is developed for this research. IIC 0-2 points presents insufficient organic causes, it does not represent the cause of pain. Non organic and non gynecologic reasons must be the cause of pain. Non organic and non gynecologic reasons must be investigated. IIC 3-5 points presents minor experienced intraabdominal infection. Secondary cases like myoma, ovarian cysts, chronic cervicitis should be considered first as reason. IIC 6 points and more presents direct organic deficiency suitable surgery is the treatment of choice of this group. PMID- 8441882 TI - [Clinical and ultrasonographic study of uterine involution in postpartum physiology]. AB - The authors monitored the involution of the uterus during the first month after childbirth by means of clinical examinations and abdominal ultrasound. 156 clinical and ultrasound examinations were performed in 77 women on D2, D7 and D28. The size of the uterus and the uterine cavity were measured on the longitudinal sections only. The other incidences, and particularly the axial incidence, made it possible to describe the aspects of the uterine cavity. Uterine involution is rapid during the first week and then slows down. By D28, the dimensions of the uterus have returned to the upper limit for the non pregnant uterus. During the first week the emptiness line is visible in one out of 13 cases. Hematometra is visible in one out of 6 cases and more frequent on D7 than on D2. It gave rise to no clinical signs. In all cases, an emptiness line was observed on day 28 postpartum. PMID- 8441883 TI - [Postpartum perineal rehabilitation by early electrostimulation at home. Preliminary study]. AB - The authors report a preliminary trial of post-partum perineal physiotherapy by functional electric stimulation at home starting from Day 15. Fifteen primipara used the technique. Perineal muscle testing and urodynamic investigations took place before Perineal muscle testing and urodynamic investigations took place before and after physiotherapy. Testing of the levators showed complete recovery in 20 p. cent of cases and partial in 80 p. cent. Urodynamic results showed a significant increase in resting urethral pressure. Acceptability of physiotherapy was perfect. The early start offered the twin advantages of better muscular recovery and easier motivation of the patient. Physiotherapy at home enabled these women, already busy, to carry out their perineal physiotherapy with minimum difficulty. PMID- 8441884 TI - [Ovarian abscess. A case of a dermoid cyst with a secondary infection]. AB - The authors report a case of an ovarian abscess presenting as acute sciatica with pyrexia in a 36-years-old woman with an intrauterine contraceptive device. Imaging (plain X-ray of abdomen and CT scan) was clear-cut, showing an air pocket as a result of abscess formation and dental calcifications which enabled a preoperative diagnosis of dermoid cyst. The outcome was successful following appropriate surgical treatment and unilateral tubo-oophorectomy. PMID- 8441885 TI - [Endometrial ossifications. A new case revealed by secondary sterility]. AB - The authors give the case history of a patient with endometrial ossification revealed by an infertility. They recall the circumstances and the discovery of this uncommon affection and they summarize references in the literature concerning aetiopathogenic theories. PMID- 8441886 TI - [Ovarian pregnancy. Four cases with review of the literature]. AB - The authors report four cases of ovarian pregnancies operated in Central Maternity of Rabat (Pr Chaoui) during a period from 1979 to 1989. In the light of literature data, they have tried to trace out the particularities of this form of extra-uterine pregnancy. Clinical symptomatology of ovarian pregnancy very often remains similar to that of tubary GEU as well as the data of complementary exams with the exception sometimes of coelioscopy. The treatment, because of diagnostic delay, is annexectomy in all cases. But it is desirable to carry out a conservative treatment in the form of partial ovariectomy. Only pathological anatomy can give the diagnosis a sense of certainty. PMID- 8441887 TI - [Study of bone vibration transmission on the child's head in utero]. AB - Analysis of the sounds transmitted from the outside world to the fetus have shown that the fetus receives sound of more than 40 decibels, regardless of the means of transmission or of the position of the mother. Below this threshold, many parameters are involved, such as the position of the mother, the method of sound transmission, but the mother's voice always seems to be have priority. PMID- 8441888 TI - [The mesorectum in females. Evolution of the fascia pelvis parietalis in pelvic dissection]. AB - The authors used dissections of adult and fetal female cadavers to describe the meso uro-genito-rectum or visceral pelvic fascia, visceral prolongation of the parietal pelvic fascia. This meso uro-genito-rectum consists of two parts: 1 The anterior part: formerly the umbilico-prevesical aponeurosis, called the meso bladder in this text. 2 The posterior part: the meso recto-vagina. While the meso rectum was already well described using the term "rectal wing" or para-rectum, knowledge of the meso-vagina under the meso-cervix (or paracervix or Mackenrodt's cardinal ligament) was poorly defined, and concerning the following in particular: * its posterior prolongation by the meso-rectum, * its relations with the middle rectal pedicle (formerly the middle hemorrhoidal pedicle),* its helicoidal appearance when in anatomical position. PMID- 8441889 TI - Mercury in primary teeth in preindustrial Norway. AB - Seventy-nine primary (deciduous) teeth were excavated in 1978 underneath the floor of the stave church in Uvdal, Buskerud County, Norway. The mercury content of 57 teeth was measured by means of cold vapor atomic absorption spectrophotometry. As a comparison, 124 primary teeth from modern Norway were analyzed. A significant statistical difference was found between the two sets of material. In the Uvdal material a correlation was found between the mercury and copper contents. For the modern material a correlation was found between mercury and lead, and between mercury and zinc. The authors maintain that the values found for the Uvdal material represent base-line values for mercury in primary teeth, and probably reflect uptake from natural environmental sources only. Furthermore, these values may be used for reference in studies of other preindustrial, as well as modern, primary teeth. Our findings also indicate a higher level of mercury in modern than in preindustrial primary teeth in Norway. PMID- 8441890 TI - Effect of fluoride on caries progression and dentin apposition in rats fed on a cariogenic or non-cariogenic diet. AB - The effect of fluoride in drinking water on the progression of dentinal caries and dentin apposition was studied in Wistar rats. The initiation of enamel caries lesions was first induced for 2 wk with S. sobrinus and a 43% sucrose diet after weaning. Thereafter the animals were fed on either a cariogenic or a non cariogenic diet and distilled water supplemented with 0, 1, 7 or 19 ppm fluoride. The areas of dentinal caries and dentin apposition were quantified after tetracycline staining. Fluoride reduced dentinal caries progression after the initiation of lesions in the presence of a cariogenic diet at a concentration of 19 ppm F, and without sucrose at 1 ppm F. The effect of fluoride in reducing dentin apposition with a cariogenic diet was dose-dependent, whereas fluoride in non-cariogenic groups had practically no effect on dentin formation. These results suggest that fluoride together with a high concentration of sucrose in the diet might have an odontoblast-mediated effect on the regulation of the progression of dentinal caries. PMID- 8441891 TI - Computerized planimetric method for clinical plaque measurement. AB - A computerized planimetric method for plaque area measurement has been developed. Using a computerized image analysis system (CIAS), the plaque area and tooth area on color slides were digitized and the number of pixels automatically counted. The proposed Plaque Percent Index (P% Index) expresses plaque area as a percentage of tooth area. The reproducibility of this method was tested and the influence of photographic technique on the P% Index was determined. The association of the Turesky modified Quigley-Hein plaque index (Q-H Index) and the P% Index was assessed. The present method was highly reproducible for the P% Index with an intraexaminer variation of 0.28% and intraexaminer correlation coefficient of 0.99. The results show that highly reproducible P% Index values with an error of less than 3.0% were obtained when the photographs were taken under the following conditions. For the buccal surfaces of anterior teeth, the slides were photographed within a 20-degree range in the horizontal plane and a 30-degree range in the vertical plane; and for the lingual/palatal surfaces of anterior teeth and the buccal or lingual/palatal surfaces of posterior teeth, the slides were photographed with an image of the whole tooth surfaces in the photographic mirrors. The comparison of the Q-H Index and the P% Index revealed that for each score of the Q-H Index the corresponding values of P% Index were wide with a significant crossover value, although a strongly positive correlation was found between the Q-H Index and the P% Index (r = 0.92, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441892 TI - Characterization of fibronectin and fibrin(ogen) fragments in gingival crevicular fluid. AB - A total of 49 crevicular fluid (CF) samples were collected with paper strips from 12 healthy adults. Each sample was eluted into sterile saline and two aliquots were drawn for SDS-PAGE, one for fibronectin and one for fibrin analysis. Peptides were transferred to nitrocellulose membranes, and fibronectin and fibrin were detected using specific antibodies. The relative amounts of different molecular forms of fibronectin and fibrin were analyzed using a laser densitometer. After the sample collection, Plaque Index, Papilla Bleeding Index and pocket depth were measured. Bone loss was estimated from the orthopanthomograms. Fibronectin fragments were seen in all CF samples. Intact fibronectin was seen in 21 samples, of which 76% were collected from periodontitis-affected sites. There was a positive correlation between the proportion of intact fibronectin and the clinical parameters. Intact fibrin and fibrin fragments were seen in all samples. Fibrin-positive material with larger molecular weight than intact fibrin was also seen in all samples. A negative correlation was found between the proportion of intact fibrin and the clinical parameters. There was no correlation between total amounts and concentrations of fibronectin and fibrin. Molecular forms of fibronectin and fibrin may affect the pathogenesis and healing of periodontal diseases, since the biologic effects of the fragments of these molecules differ from those of the intact molecules. PMID- 8441893 TI - Objective and subjective efficacy evaluation of various polymer-based saliva substitutes. AB - Various polymer solutions with and without surfactants were evaluated regarding their lubricating properties on the oral mucosa. After rinsing with the solutions, the oral mucosal friction value was registered with a probe (objective effect). After each rinsing occasion at home, the patients answered a questionnaire (subjective effect). None of the tested polymers showed a longer, clinically significant effect than the other ones. Some of them had the same effect as substitutes available on the Swedish market. PMID- 8441894 TI - Salivary stimulation by chewing gum and lozenges in rheumatic patients with xerostomia. AB - The effect of chewing gum and lozenges in relieving the signs and symptoms of xerostomia was studied in a 2-wk cross-over clinical trial in 18 rheumatic patients with dry mouth symptoms and low salivary flow rates. Resting flow was measured before (PRESTIM) a chewing stimulated flow rate test (STIM), and also 5 min after (POSTSTIM). STIM flow (mean 1.0 ml/min) was not affected by the test regimens. In the lozenge regimen, mean PRESTIM flow in the group increased from 0.11 to 0.14 ml/min and POSTSTIM from 0.10 to 0.13. In the chewing gum regimen, PRESTIM flow (mean 0.13 ml/min) did not change, whereas POSTSTIM flow increased from 0.13 to 0.16 ml/min. In terms of patients' preferences, chewing gum and lozenges were ranked equal. Both these physiologic stimuli had few side-effects. Subjective symptoms were relieved in about one-third of the subjects, but relief was not always verified by improved flow rates. The regimens were not found to influence buffering capacity; salivary counts of mutans streptococci, lactobacilli, and candida; or oral sugar clearance time. PMID- 8441895 TI - Oral mucosal friction and subjective perception of dry mouth in relation to salivary secretion. AB - Assessment of oral mucosal friction and subjective perception of dry mouth was performed during treatment with thiazide diuretic bendroflumethiazide (2.5 mg o.d.) or placebo in a randomized, double-blind, cross-over study (2 x 2 wk) in 34 healthy volunteers. Treatment with bendroflumethiazide was associated with a 10% reduction in the stimulated whole saliva secretion rate and a 15% reduction in the salivary sodium concentration, as compared with placebo. Oral mucosal friction was concomitantly measured on the buccal mucosa and on the mucosa of the lower lip by means of a newly developed sliding friction device. In addition, a questionnaire was used to evaluate how the treatment was subjectively perceived with regard to symptoms of dry mouth. Mucosal friction of the lower lip increased significantly during treatment with bendroflumethiazide, as compared with placebo. When the test subjects, regardless of pharmacologic treatment, were divided into groups according to subjective perception of dry mouth, the dry mouth group showed significantly lower resting and stimulated flow rate and higher mucosal friction in comparison to the nondry group. When, in addition, pharmacologic treatment was also considered, the differences between the dry and the nondry group were restricted to resting whole saliva flow rate and mucosal friction during bendroflumethiazide treatment. It is concluded that resting whole saliva flow rate is the best predictive factor for evaluating subjectively perceived dry mouth. However, the sensitivity of the developed sliding friction device is capable of detecting minor changes in salivary secretion rate. In addition, measurements of oral mucosal friction may serve as an easily available method to complement sialometry when evaluating, for example, drug-induced dryness of the mouth. PMID- 8441896 TI - Contact allergy to Duraphat. AB - Skin-sensitizing rosin is present in Duraphat, a fluoride varnish used all over the world. Two cases of hypersensitivity to Duraphat are presented: a dental nurse with dermatitis of the hand and a patient with allergic contact stomatitis. PMID- 8441897 TI - Fluoride acquisition on and in fluorotic human enamel after topical application in vitro. AB - The uptake of alkali soluble and alkali insoluble fluoride on and in fluorotic enamel was investigated in vitro. Teeth from Kenya, assigned score 3 in accordance with Thylstrup-Fejerskov's fluorosis index, were used. The enamel was treated with either a neutral 2% NaF solution, a 0.2% NaF solution (pH 5.5), or the supernatant from a 0.1% NaF-containing toothpaste (pH 7). The treatment time was 1 h. The reaction product formed on the enamel was analyzed by KOH extraction and acid etching. Significantly higher amounts of alkali soluble fluoride were formed on the enamel from the 2% and 0.2% NaF solutions, as compared with the control. There was also a significant increase in the firmly bound fluoride after treatment with the neutral 2% NaF solution. PMID- 8441898 TI - Radiographic screening examination: frequency, equipment, and film in general dental practice in Denmark. AB - The aim of the present study was to evaluate types and frequencies of radiographic screening examinations, and radiographic equipment and film used in general dental practice in Denmark. A questionnaire was mailed to 400 randomly selected dental practitioners. A total of 258 questionnaires were returned, out of which 249 were analyzed. Two-thirds of the respondents performed radiographic screening examinations, of which bitewing-screening was the one most frequently used for first-visit and regular patients. The more recent their graduation year, the more apt were dentists to perform radiographic screening examinations. More than 40% of the dentists had radiographic units operating at a voltage capacity of 60-70 kV, and more than 50% had facilities for automatic or semiautomatic processing. Only one-quarter of the respondents used the Kodak Ektaspeed film (E speed film). The results show that radiographic procedures and film used in general dental practice are not always in accordance with guidelines and recommendations. PMID- 8441899 TI - Histochemical characterization of pig masseter muscle: an animal model. AB - Masseter muscle autopsies were obtained from six different areas of six pigs. The autopsies were stained for the demonstration of myosin ATPase activity by means of a conventional histochemical technique. As compared with human masseter, the pig masseter muscle contained more type II fibers. But, like the human masseter, the pig muscle had a varying distribution of fiber types in the different autopsy areas, a distribution which might be the result of an adaptation to carry out special functions such as chewing, swallowing, and jaw posture. The fiber type distribution in the pig masseter also varied among individuals, probably reflecting various levels of utilization of the muscles besides different genetic influences. Moreover, pig masseter contained fibers of intermediate staining intensity (IM fibers), a fiber type rarely seen except in human masticatory muscles. In conclusion, we consider the pig masseter to be a useful animal model to study muscular adaptations to altered function in the orofacial region. PMID- 8441900 TI - Correlation between depth of cure and surface hardness of a light-activated resin. AB - Microfilled test specimens were polymerized for 40 s with 10 different curing units. The specimens were stored for 7 days at 36 +/- 0.5 degrees C, and then the hardness of the surface was measured. The depth of cure of the 10 units was also measured, but no correlation was found between surface hardness and depth of cure. Even inferior curing units were able to polymerize the surface just as effectively as good light sources. The conclusion is that one cannot use the surface hardness of an irradiated resin to assess the quality of a curing unit. PMID- 8441901 TI - Dental plaque and caries on permanent first molar occlusal surfaces in relation to sagittal occlusion. AB - This study examines the influence of sagittal occlusion on occlusal plaque formation in permanent first molars (PFM) in 72 7-10-yr-olds before loss of primary second molars. Of a total of 288 PFM, 140 (49%) were sealed and 23 (8%) filled. Occlusal plaque was recorded at two levels of examination: 1) visible plaque on the entire surface and 2) detailed macromorphologic mapping. Enamel caries was recorded after professional tooth cleaning. After 48 h without tooth brushing, plaque examinations were repeated. Stone models were used for 1) identification of interocclusal contact areas and 2) classification of sagittal molar occlusion. The detailed mapping of plaque on unfilled surfaces showed a clear pattern of preferential locations related to the macromorphology of the occlusal surfaces. Active caries was restricted to those anatomic structures where plaque accumulated. 48-h median plaque values on mandibular molars in normal and with one cusp distal occlusion were significantly lower (P < 0.01) compared to surfaces in 1/4, 1/2 and 3/4 distal molar occlusion. Maxillary molars with normal and with 1 cusp distal occlusion had lower median plaque values than other sagittal occlusion categories. In general, however, plaque scores were higher in maxillary teeth because more than 2/3 of these teeth were without occlusal contact in the distal part. Mandibular occlusal surfaces in normal and with one cusp distal occlusion had significantly fewer active lesions than teeth with 1/4, 1/2 and 3/4 cusp distal occlusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441902 TI - Perfusion of the human distal colon and rectum evaluated with endoscopic laser Doppler flowmetry. Methodologic aspects. AB - The aim of this study was to evaluate methodologic aspects of colonoscopic laser Doppler flowmetry. A Periflux PF1d flowmeter, set to 4 kHz/0.2 sec, with an endoscopic probe (PF 109) was used. In 20 patients, with a median age of 70 years and without colonic disease, flux was recorded at 10, 40, 30, 20, and again at 10 cm from the anal verge. A median of three repeated recordings were made at each level, to calculate average flux and spatial variation. Median flux was 158 (150 167) perfusion units, and the coefficient of variation of repeated recordings 0.14 (0.12-0.17). There was no regional variation, and no increase in flux at 10 cm from the start until the end of the procedure. Pressure of the probe against the bowel wall and severe distention significantly reduced the flux. The interference of light from the endoscopic light source on the flux could not be predicted. It differed with different light sources, and also with the length of probe coming out of the colonoscope--that is, the distance from the light to the measurement point. To avoid the problem, the light source should be turned off while recording. PMID- 8441903 TI - Reduced sensitivity to intra-oesophageal acid in patients with reflux-induced strictures. AB - Patients presenting with benign reflux-induced oesophageal strictures often have no antecedent symptoms of reflux, which might be a consequence of decreased oesophageal sensitivity. This has been investigated in 36 patients with strictures and 30 patients with uncomplicated oesophagitis by means of a visual analogue scale (0 to 10) to assess preceding symptoms and acid perfusion tests to assess oesophageal sensitivity. Patients with strictures had lower symptom scores (median, 2.7) than those with uncomplicated oesophagitis (median, 4.85) and were more likely to have a negative acid perfusion test (18 of 28 compared with 6 of 23, respectively; p < 0.05). Furthermore, the volumes of acid perfused at the onset of symptoms in the stricture group (median, 80 ml) were greater than in the oesophagitis group (median, 40; p < 0.05). These results support the hypothesis that patients who develop reflux-induced strictures have decreased sensitivity to intra-oesophageal acid. This may be a factor in the pathogenesis of reflux induced strictures. PMID- 8441904 TI - The incidence of reflux oesophagitis. A study of endoscopy reports from a defined catchment area in Sweden. AB - Very few epidemiologic data on reflux oesophagitis are available. To estimate the incidence of reflux oesophagitis, all reports (n = 6733) of upper gastrointestinal endoscopy performed in patients aged > or = 16 years and living in a defined catchment area of 226,776 inhabitants were examined during a 2-year period. The incidence of reflux oesophagitis was calculated to be 120 per 100,000 inhabitants, and most of the incident cases (88%) were uncomplicated oesophagitis with single or multiple erosions. The incidence of complicated oesophagitis and Barrett's esophagus was 5.6 and 1.7 per 100,000, respectively. The mean age of all incident subjects was 56 +/- 18 years (range, 17-88 years) with a male to female ratio of 2:1. The severity of oesophagitis increased significantly with age (p = 0.0003), and most (75%) of the patients with complicated oesophagitis were > or = 60 years of age. Men had more severe grades of oesophagitis than women (p = 0.0003), and endoscopic evidence of peptic ulcer disease was observed in one of five patients. PMID- 8441905 TI - Interobserver variation in the endoscopic diagnosis of reflux esophagitis. AB - The interobserver variation among three experienced endoscopists in the endoscopic diagnosis and grading of reflux esophagitis was investigated in 150 dyspeptic patients. The interobserver variation was analyzed with kappa statistics to correct for the extent of agreement expected by chance alone. The observers diagnosed esophagitis in 22.7%, 32.7%, and 35.3% of the patients, respectively (p < 0.0002). Kappa values for grade-1 esophagitis varied from 0.34 to 0.47, a level generally considered to signify poor agreement, and despite partial agreement on the diagnosis in the individual patient there was almost complete disagreement on the features used to characterize grade 1. Kappa values for diagnosing erosive esophagitis (grades 2-4) were 0.68-0.79. Considering all three observers and all grades of esophagitis (grades 0-4) the overall chance corrected agreement was 0.55. In patients with low-grade esophagitis without reflux-like dyspepsia and when the observers expressed uncertainty in the diagnosis, the agreement rates were particularly poor. Due to a large chance corrected interobserver variation, the endoscopic diagnosis grade 1 esophagitis is not reliable and thus may be problematic as a selection criterion for clinical trials. Interobserver variation on the presence of erosive/ulcerative esophagitis is acceptable and comparable to the level for peptic ulcer. PMID- 8441906 TI - Nucleation time and fatty acid composition of lecithin in human gallbladder bile. AB - We investigated the relationship between bile nucleation time and the fatty acid composition of biliary lecithin in human gallbladder bile. Bile samples from patients with cholesterol gallstones nucleated more rapidly than those from patients with noncholesterol gallstones or no stones. The biliary cholesterol concentration was highest in the cholesterol gallstone group and was correlated with the molar percentage of linoleic acid and arachidonic acid, with these percentages also being higher in bile from the cholesterol gallstone patients than in bile from the other two groups. In addition, the mucous glycoprotein concentration in bile was also significantly higher in the cholesterol gallstone group. Thirty-three patients in the no-stone group showed bile nucleation times of less than 21 days. Higher concentrations of cholesterol and mucous glycoprotein and higher molar percentages of arachidonic and linoleic acid were noted in these patients. These findings suggest that in humans, hepatic cholesterol hypersecretion is associated with the increased unsaturated fatty acid proportion in biliary phospholipids and gallbladder mucin hypersecretion, thereby causing rapid cholesterol crystal nucleation. PMID- 8441907 TI - Dihydropyridine calcium channel antagonists disrupt migrating myoelectric complexes and counteract intestinal disorders associated with morphine withdrawal diarrhea. AB - The effects of two dihydropyridine (DHP) calcium channel antagonists, nifedipine and nimodipine, on migrating myoelectric complexes (MMCs) of the small intestine were studied in naive and morphine-dependent rats. In addition, the effects of two other calcium channel antagonists, verapamil and diltiazem, on the MMCs were investigated. Nifedipine (1.0-4.0 mg kg-1 intravenously) or nimodipine (1.0-4.0 mg kg-1 intravenously) had an inhibitory effect on the spontaneously occurring MMCs, whereas verapamil (2.5-5.0 mg kg-1 intravenously) or diltiazem (2.5-5.0 mg kg-1 intravenously) had no effect. Bay K 8644 (0.25 mg kg-1 intravenously), a DHP calcium channel agonist, instantly reversed the inhibition induced by nifedipine or nimodipine. When given alone, Bay K 8644 induced irregular spiking activity. In morphine-dependent rats with regular MMCs naloxone (1.0 mg kg-1 intravenously) induced intense spiking activity and profuse diarrhea. Nifedipine (2.0 and 4.0 mg kg-1 intravenously) and nimodipine (2.0 and 4.0 mg kg-1 intravenously) given before naloxone prevented the intense, abstinence-evoked spiking and associated diarrhea. In healthy volunteers nimodipine at an infusion rate of 2 mg h-1 for 4 h did not inhibit the fasting motility pattern. Our findings indicate that DHP binding sites are involved in the regulation of MMC in the rat and that drugs acting as antagonists at these sites can be used to suppress morphine withdrawal diarrhea and, tentatively, other functional disorders of the intestine. PMID- 8441908 TI - Portacaval shunt increases the trophic effect of cholecystokinin on the rat pancreas. AB - The trophic effect of cholecystokinin (CCK) on the pancreas was examined in portacava-shunted (PCS) rats. Exogenous CCK-8s and the CCK-A receptor antagonist devazepide were infused continuously by means of osmotic minipumps. HyperCCKemia of endogenous origin was induced by pancreaticobiliary diversion (PBD), which is known to cause growth of the pancreas. The results showed that PCS as such was without a trophic effect on the pancreas, whereas the combination of CCK-8s and PCS or PBD and PCS increased the trophic effects on the pancreas compared with CCK-8s or PBD alone. Moreover, the trophic effects of PBD and of the combination of PBD and PCS could be prevented by CCK-A receptor blockade (devazepide infusion). The results suggest that the capacity of the pancreas to respond to CCK is exaggerated--for as yet unknown reasons--after PCS. PMID- 8441909 TI - Smoking and intestinal absorption of oral polyethylene glycols in Crohn's disease. AB - Intestinal absorption of orally administered polyethylene glycols with molecular weights of 634-1250 was investigated in 55 patients with Crohn's disease and in 20 healthy controls and was related to smoking habits at the time of testing. In the Crohn patients the polyethylene glycol absorption was also related to smoking habits at the time of diagnosis. Absorption of polyethylene glycols was impaired in Crohn patients compared with controls, but within both groups no difference was found among smokers, ex-smokers, and never-smokers (p > 0.05). Among the Crohn patients, those who smoked at the time of diagnosis had less impaired absorption (p < 0.02) of the smaller polyethylene glycols (634-942 Da) than those who did not. These data do not support the concept of altered intestinal permeability as the mechanism by which smoking influences Crohn's disease. PMID- 8441910 TI - Randomized clinical trial of furazolidone for typhoid fever in children. AB - The efficacy of furazolidone and chloramphenicol was compared in a randomized trial involving 133 children with bacteriologically confirmed typhoid fever. Sixty-five children were randomized to receive furazolidone, 7.5 mg/kg/day, and 68 children to receive chloramphenicol, 75 mg/kg/day. Both drugs were administered orally. The clinical characteristics of the two treatment groups were comparable on admission. All the strains of Salmonella typhi isolated from the furazolidone group were susceptible to furazolidone. However, of the 68 strains of S. typhi isolated from the chloramphenicol group, 10 were susceptible and 58 were resistant to chloramphenicol. Clinical and bacteriologic cure was observed in 56 (86.2%) children treated with furazolidone and in 35 (51.5%) children given chloramphenicol who were infected with S. typhi strains, irrespective of susceptibility pattern (P = 0.00003). Cure was achieved in 86.2% of furazolidone recipients and 90.0% of chloramphenicol recipients who were infected with strains of S. typhi susceptible to both drugs (P = 0.6). The difference in cure rate was statistically significant (P = 0.000003) when the two treatment groups infected with furazolidone-susceptible but chloramphenicol resistant strains of S. typhi were compared. There was no relapse or carriers in either of the groups. Furazolidone appears to be a satisfactory alternative to chloramphenicol in the treatment of typhoid fever caused by chloramphenicol resistant strains of S. typhi. PMID- 8441911 TI - Gastric mucosal microcirculation and purine nucleotide metabolism after retransfusion of rats in hemorrhagic shock. AB - Gastric mucosal microcirculation and purine nucleotide metabolism were studied after hemorrhagic shock and retransfusion in rats. The number of perfused microvessels and the concentration of adenosine triphosphate, adenosine monophosphate, inosine monophosphate, inosine, hypoxanthine, xanthine, and uric acid were investigated in mucosal biopsy specimens after 15 or 45 min of hemorrhagic shock and after 15 min of shock followed by 30 min of retransfusion. During shock a dephosphorylation of nucleotides and a decrease in the number of perfused microvessels occurred, the more the longer the duration of the shock period. Retransfusion led to an additional reduction in the number of perfused microvessels, but there was a partial restoration of high-energy phosphate metabolites in those areas of the mucosa which maintained a blood flow. The results indicate that there is a renewal of energy stores in gastric mucosa after hemorrhagic shock and reperfusion, although parts of the vascular bed are not reperfused. PMID- 8441912 TI - Effect of once daily intravenous and oral omeprazole on 24-hour intragastric acidity in healthy subjects. AB - The effect of repeated once daily administration of 20 mg omeprazole orally and 10 mg and 40 mg intravenously on 24-h intragastric acidity was studied in nine healthy subjects. On day 1, 20 mg orally and 10 mg intravenously reduced integrated intragastric acidity by 18% and 15%, respectively (NS). On day 5 the reduction had increased to 60% and 53%, respectively (p < 0.05). The first dose of 40 mg intravenously produced a reduction of 71% (p < 0.05) with no further increase during continued administration. An increase in plasma omeprazole concentrations by 56% (p < 0.05) was seen during repeated dosing with 40 mg intravenously, while no significant change occurred with the two other doses. Thus once daily administration of 10 mg omeprazole intravenously produced an effect on 24-h intragastric acidity comparable to that of once daily administration of 20 mg omeprazole orally. However, for both these dosage regimens it took a few days before their maximal effect was obtained. Parenteral administration of 40 mg omeprazole produced, already on the first day of treatment, an effect similar to that seen after 5 days of oral administration of 20 mg omeprazole or intravenous administration of 10 mg and can therefore overcome this initial delay in drug action. The reduction of 24-h intragastric acidity seen in the present study appeared to be lower than that seen in a similar study in duodenal ulcer patients, a finding not explained by differences in age or pharmacokinetics. PMID- 8441913 TI - Endoscopic management of malignant biliary obstruction. Is stent size of 10 French gauge better than 7 French gauge? AB - This study reviews 139 endoscopic biliary drainage procedures in 89 patients with malignant biliary obstruction. We compared the performance of straight 7 FG (31 patients; 36 procedures) and 10 FG (45 patients; 84 procedures) stents with regard to early complication rate and late clogging. The stent patency of all single 7 FG and all single 10 FG stents were 67 days and 144 days (p = 0.11), respectively. A complication was seen in 13.9% of the procedures with a 7 FG stent and in 16.7% of the procedures with a 10 FG stent inserted. When 2 7 FG stents (13 patients; 19 procedures) were used, the figures were 110 days and 21.1%, respectively. High stenosis was more frequent in this group. We found no significant differences in the performance of a single 7 FG and a single 10 FG stent, but there was a trend towards a longer patency and a higher complication rate of a single 10 FG stent compared with a single 7 FG stent. PMID- 8441914 TI - Peritoneal mesothelioma without ascites formation. AB - A case of malignant peritoneal mesothelioma without development of ascites is described. The patient had a 1-year history of non-specific symptoms preceding this diagnosis. The insidious onset of clinical signs, the diagnostic procedures, and the pathologic findings are discussed. PMID- 8441915 TI - Changes in the expression of Ig-associated proteins on B lymphocytes activated by anti-IgM antibodies. AB - Binding of antigen to receptor complexes on B cells elicits a cascade of intracellular signalling events leading to proliferation and, together with T cell help, Ig secretion. Components of the antigen receptor (AgR) complex have been demonstrated to be either covalently bound or associated with surface Ig (sIg) molecules. The function of these proteins is still unknown. In order to address this question, we have stimulated B cells with anti-mu antibodies and have studied possible changes in the expression of AgR complexes. After anti-mu stimulation, the IgM molecules disappeared rapidly from the cell surface together with the covalently bound proteins. The IgM molecules were internalized and probably degraded. The IgM-associated heterodimer Ig-alpha/Ig-beta was also removed from the cells, leaving the IgD-associated heterodimer unaffected. Two proteins showed an enhanced association with sIg after 15 min and then were gradually removed from the cell surface. Two other proteins became increasingly attached to sIg. This association remained stable for the rest of the culture period (up to 4 h). Further studies are underway to characterize these proteins more closely and to examine possible interactions with downstream members of the signalling cascade. PMID- 8441916 TI - Anchorage and lymphocyte function: extracellular matrix substrata control morphogenesis and interleukin production but have minor effects on DNA synthesis. AB - Contact with collagen and fibronectin substrata triggers disruption of aggregates of activated lymphocytes, pseudopodia formation and migration of these lymphocytes onto the substrata. Monoclonal antibodies to the alpha 4 and alpha 5 chains of beta 1-integrins inhibit cell substrate adhesion and aggregate disruption on fibronectin substrata. A rat monoclonal antibody to the beta 1 integrin chain inhibits lymphocyte adhesion to collagen. Two-dimensional (2D) and three-dimensional (3D) collagen substrata have virtually the same capacity to abrogate lymphocyte aggregation. Fibronectin substrata trigger the initial phase(s) of aggregate disruption as effectively as collagen but the later part of the disruption process is relatively incomplete. Serum-coated plastic does not cause aggregate disruption. These results indicate that disruption of lymphocyte aggregates is a specific event induced via cell surface receptors for extracellular matrix (ECM) components. A major difference between lymphocytes on 2D and 3D extracellular matrix substrata seems to be that the cells detach from the former whereas on the latter infiltration dominates over detachment. Collagen and fibronectin substrata are non-mitogenic for lymphocytes but they can modulate lymphocyte activation induced by allogeneic cells and Con A. Thus, 3D collagen substrata augment and prolong such induced DNA synthesis, although they slightly delay entry into the S-phase and decrease IL-2 production. Collagen substrata, particularly in 3D form, also augment the DNA synthesis of preactivated lymphocytes above the magnitude on serum-coated plastic. The nature of the substratum determines IL-1 production. Accordingly, the spontaneous IL-1 production by mononuclear cells is substantially lower on collagen substrata than on plastic surfaces coated with serum or BSA. However, factors which induce IL-1 production (e.g. Con A or LPS) are more effective on collagen than on serum coated plastic. Abrogation of cell aggregation, induction of morphogenesis and motile behaviour as well as control of IL-1 synthesis thus constitute major effects of ECM substrata on cells of the immune system. An additional but relatively minor influence of ECM substrata on these cells, as suggested by the present results, is exerted via modulation of DNA synthesis. PMID- 8441917 TI - Pancreatic gangliosides delay the onset of insulitis and hyperglycaemia in the low-dose streptozotocin mouse model. AB - Gangliosides have been shown to modulate autoimmune phenomena in experimental diabetes. The effects of a pancreatic ganglioside preparation or of a commercial brain ganglioside mixture on the insulitis and blood glucose levels in the low dose streptozotocin mouse model of diabetes have been investigated. Fifty-five C57BL/6J male mice were grouped as follows: Group 1 (n = 20) was injected intraperitoneally with repeated low doses of streptozotocin; Group 2 (n = 10) received streptozotocin as above but was also injected with a pancreatic ganglioside preparation equivalent to 2 micrograms sialic acid 2 h before each streptozotocin dose; Group 3 (n = 15) received streptozotocin and brain-derived gangliosides in the same dose as that of pancreatic gangliosides; Group 4 (n = 10) consisted of normal animals. Half of the mice were killed on day 12 and the others on day 24 from the beginning of treatment. On day 12, among the streptozotocin-injected animals only those treated with pancreatic gangliosides remained normoglycaemic, whereas on day 24 all streptozotocin mice were hyperglycaemic. Such a result paralleled the data pertaining to insulitis scores. In conclusion, pancreatic gangliosides have a short-term protective role on the development of diabetes in the low-dose streptozotocin model, an effect therefore linked to tissue-related differences in the glycosphingolipid composition. PMID- 8441918 TI - Effect of heat shock on susceptibility of normal lymphoblasts and of a heat shock protein 70-defective tumour cell line to cytotoxic T lymphocytes in vitro. AB - The effect of heat shock pretreatment of target cells on their lysability by cytotoxic T lymphocytes was analysed. Killing of Concanavalin A-stimulated normal lymphocytes by minor or major histocompatibility antigen-specific cytotoxic T lymphocytes is unchanged or even slightly enhanced after heat shock, whereas cells of the myeloma line Y3, which is derived from one of the lymphocyte donor strains, become nearly resistant to killing after the same pretreatment. Cold target inhibition experiments show that heat-shocked cells are recognized specifically and that untreated and heat-shocked target cells possess similar inhibitory potential. Y3 cells are unable to express the strongly heat-inducible heat shock protein of 70 kDa (hsp70) after heat shock; the acquired resistance is thus independent of hsp70 induction. Possible mechanisms of the different lysability seen in lymphoblasts and tumour cells after heat shock are discussed. PMID- 8441919 TI - Responsiveness for mouse IgG2b antibodies to the human alpha/beta T-cell receptor/CD3 complex: evidence for genetic determination and low grade antibody cross-linking not mediated by known Fc gamma receptors. AB - Mouse IgG2a and IgG3 antibodies directed to the human T-cell receptor/CD3 complex stimulate peripheral blood mononuclear cells in almost all individuals. By contrast, responder and non-responder individuals exist for the stimulatory effect of mouse IgG1 and IgG2b antibodies. Whereas responsiveness to IgG1 antibodies is rather frequent (60-70%) and is known to be determined by an Fc gamma RII polymorphism on the accessory cells, little is known about the underlying factors of the rare (6%) IgG2b responsiveness. In this study it is shown that (1) IgG2b responsiveness is genetically determined with a dominant pattern of inheritance; (2) IgG2b responsiveness is determined by a radioresistant feature of responder accessory cells which can be substituted by artificial cross-linking, but not by IL-1 beta or IL-2; (3) stimulation of peripheral blood mononuclear cells of an IgG2b responder by IgG2b antibodies requires rather high antibody concentration compared with stimulation by IgG2a antibodies; (4) the stimulation leads to proliferation and IL-2 receptor expression, but no measurable IL-2 production; (5) antibody binding to known Fc gamma receptors (Fc gamma RI, Fc gamma RII, Fc gamma RIII) is not involved in the stimulatory effect of the IgG2b antibodies in responders. These results demonstrate that responsiveness to IgG2b antibodies against the TcR/CD3 complex depends on a genetically determined feature of accessory cells that is not identical with any of the known Fc gamma receptors. Most likely, the stimulatory effect observed in IgG2b responders is explained by a low grade cross-linking of the antibody by a not yet identified polymorphic structure on the surface of accessory cells. PMID- 8441920 TI - Association of pepsin with type II collagen (CII) breaks control of CII autoimmunity and triggers development of arthritis in rats. AB - Lewis rats develop arthritis after immunization with heterologous but not homologous rat type II collagen (CII). We have observed that if the rat CII is prepared by pepsin digestion without subsequent extensive purification, it is arthritogenic in Lewis rats. To address whether pepsin in the CII preparations contributed to the development of arthritis and whether this was associated with the induction of an immune response to CII, Lewis rats were immunized with rat CII of various degrees of purity and with various pepsin contents. After immunization with a crude preparation of CII, containing relatively large amounts of pepsin, Lewis rats developed arthritis with an incidence of 80% together with a strong anti-CII autoantibody production. Further purification of the CII on DEAE-Sepharose, which removes pepsin, eliminated the arthritogenic properties and the capacity to activate CII-specific B cells. Likewise, lathyritic CII, prepared without pepsin, induced neither a CII-specific immune response nor arthritis. If, however, pepsin was added to non-arthritogenic batches of rat CII, arthritis appeared at an incidence of 40%. By using an ELISPOT technique to detect antigen specific interferon-gamma-producing T cells and antibody-producing B cells, the immune response to CII and pepsin can be evaluated. Eleven days after immunization with lathyritic CII and pepsin, a B-cell response towards both CII and pepsin was seen. Pepsin-specific T cells were also seen at day 11, but CII specific T cells did not appear until day 14 after immunization. In addition, a weak CII-specific proliferative response of the T cells could be demonstrated at day 14 but not at day 11 or 12. These data show that pepsin plays an important role in the triggering of a CII-specific immune response. We suggest a carrier hapten mechanism where pepsin acts as a carrier and CII as a 'hapten' which will activate CII-specific B cells. Subsequently these CII-specific B cells will break the T-cell tolerance and evoke a T-cell-mediated immune response towards CII. PMID- 8441921 TI - Human B lymphocyte in vitro response to the group B streptococcal type III capsular carbohydrate. AB - Anti-group B streptococcal type III polysaccharide-specific human B cells from the peripheral circulation can be activated and detected in an in vitro culture system. It is possible to detect both IgM- and IgG- producing cells from both seropositive and seronegative donors. The specificity of the response was demonstrated by inhibition with excess liquid phase antigen and the use of related but antigenically distinct control antigens. The response was absent without the addition of T cells, optimal at 10% and 25% T cells respectively for IgM- and IgG-secreting cells, and undetectable using 50% T cells. The optimal antigen concentration for in vitro B-cell activation is 2.5 x 10(-4) micrograms/ml. Cells from 5 of 6 seropositive donors and 3 of 7 seronegative donors produced specific IgM antibody after culture with antigen. We conclude that the control of the human antibody response to the group B streptococcal type III polysaccharide is influenced by T cells. The response seen in the culture system may be of value in assessing future vaccine candidates designed to prevent neonatal infections. PMID- 8441922 TI - Modification of the complement binding properties of polystyrene: effects of end point heparin attachment. AB - In recent years, conjugation of heparin to biomaterials has been shown to improve its biocompatibility. The purpose of the present work was to compare complement activation and binding of C3 to unmodified and heparin-treated polystyrene surfaces of microtitre plates. When polystyrene was incubated with human serum, C3 was deposited on the surface by both adsorption and binding dependent on activation of the classical (CPW) and alternative (APW) pathways. After end-point attachment of heparin, significant C3 deposition, although at reduced levels, occurred only by CPW-mediated mechanisms, while adsorption and APW-mediated binding were strongly reduced. Generally, the modified surface bound lower amounts of protein, e.g. serum albumin and IgG, than the unmodified. By contrast, it had increased affinity for C1q which leads to binding of C1 and activation of complement via the CPW. Nevertheless, the net effect of the surface modification on the complement reaction was an overall reduction of C3 binding due to obliteration of APW. This can be related to an enhanced factor H/I-dependent down regulation of C3b and to the lowered protein-adsorbing property of the surface, both of which have inhibitory effects on APW and on the C3 shunt-dependent activation of the complement system. PMID- 8441923 TI - Intrathecal synthesis of anti-Borrelia burgdorferi antibodies in neuroborreliosis: a study with special emphasis on oligoclonal IgM antibody bands. AB - Pre- and post-treatment (up to 3-26 months after antibiotic therapy) humoral immune responses were investigated in five neuroborreliosis patients. Anti Borrelia (B.) burgdorferi IgG and IgM antibodies in CSF and serum were quantitated by capture ELISA. Agarose gel isoelectric focusing (AIF) and protein blotting were used to detect oligoclonal IgG and IgM bands as well as oligoclonal anti-B. burgdorferi IgG and IgM antibodies. These latter components were visualized by transfer to antigen-coated membranes (immunoblot) and immunoenzymatic staining. By ELISA, intrathecal anti-B. burgdorferi IgG and IgM antibody synthesis was detected in all initial specimens and continued 3-26 months after antibiotic therapy in four and three cases, respectively. AIF with protein blotting showed oligoclonal bands of total IgG as well as total IgM in the initial CSF specimens of all patients and persistence of such components occurred in four and five cases, respectively. By AIF and immunoblot, oligoclonal anti-B. burgdorferi IgG and IgM antibody bands could be detected in the CSF of every patient. IgG antibody bands were present in all initial CSF samples. The first specimen of one patient was negative for IgM antibody bands but such components appeared 3 weeks later. Oligoclonal CSF anti-B. burgdorferi IgG antibody components persisted over the entire follow-up periods in all but one case where they disappeared 6 weeks after treatment. The oligoclonal IgM antibodies in CSF vanished in two cases (after being present up to 4 and 11 months after antibiotic therapy) while they persisted over the entire (3-6 months after antibiotic therapy) follow-up periods in three cases. The specificity of the IgM antibody immunoblot technique was corroborated by control experiments, including antibody absorption studies and use of 41 kDa flagellar antigen. PMID- 8441924 TI - Immunoelectrophoretic characterization of insulin monomers and polymers. AB - Insulin monomers and polymers were analysed by quantitative immunoelectrophoretic procedures. The Zn-insulin hexamer dissociated reversibly by dialysis against the Zn-free electrophoresis buffer. The Zn-insulin polymers showed precipitin reactions of partial identity. Monomeric salt-free insulin migrated as soluble immune complexes in the antiserum gel. The insulin monomer did not absorb the precipitating antibodies against the Zn-insulin polymers. Thus the polymer structure creates antigenic epitopes absent from the insulin monomer. As insulin is probably released from the beta cells in the relatively stable form of Zn insulin hexamers, selective monomer assays might underestimate the total content of immunoreactive insulin in the biological fluids. Electroimmunoassay of Zn insulin immunoreactive antigens in human urine defines a normal reference range of 10-25 ng/ml. PMID- 8441925 TI - Thoughtful restraint. PMID- 8441926 TI - Prostaglandins: viable therapy in gastric ulceration. AB - Gastric ulceration is a complex, multifaceted, pluricausal illness. The pathophysiology of gastric ulcer disease continues to be unclear. The mainstay for pharamacological management of gastric ulceration exists in reduction or neutralization of gastric acid secretion through administration of histamine H2 receptor blockers such as cimetidine and ranitidine. Recent studies show however that the majority of patients experiencing gastric injury exhibit normal or below normal levels of HC1 and pepsin secretion which leaves question to the effectiveness of acid reduction therapy. A viable alternative to H2 receptor blockade is to prevent mucosal injury by maintaining the integrity of the mucosal barrier through administration of prostaglandin analogues. This cytoprotection may reduce gastric damage while maintaining normal acid secretion. Our purpose is to review prostaglandins as a potential therapeutic treatment of gastric and duodenal injury and explore the role of prostaglandins as natural physiological defense mechanisms against gastroduodenal mucosal damage. We also discuss several gastric mucosal damaging agents such as nonsteriodal anti-inflammatory drugs, alcohol, and stress along with comparisons of effectiveness between prostaglandin analogues and H2 receptor blockers in reparation and prevention of injury caused by these agents. PMID- 8441928 TI - The transdermal route of drug administration. PMID- 8441927 TI - Assessing extracranial carotid stenosis: magnetic resonance angiography, duplex scanning, and digital angiography. AB - Recent data have demonstrated the efficacy of carotid endarterectomy in patients with severe, symptomatic carotid stenosis. In this context, our study analyzes the role of carotid testing with magnetic resonance angiography and carotid duplex scanning, as compared to arterial digital subtraction angiography. PMID- 8441929 TI - Fall prevention: a challenge to the health care team. PMID- 8441930 TI - Biomechanical study of C1-C2 posterior arthrodesis techniques. AB - Fifteen cervical spines from cadavers were used to compare the rotational and translational stability of the Brooks fusion, a fusion construct using Halifax interlaminar clamps, and the Gallie fusion. The Brooks and Halifax clamp constructs exhibited significantly greater rotational and translational stiffness than the Gallie construct (P < 0.001). The Halifax clamp construct exhibited greater rotational stiffness and equal translational stiffness when compared with the Brooks construct (P < 0.05). The Brooks and Halifax fixation constructs provided superior fixation but presented technical challenges. The Gallie construct is less technically demanding but provides less stable fixation. PMID- 8441931 TI - A biomechanical study of odontoid fractures and fracture fixation. AB - The purpose of this study was to measure the stability of the odontoid process after fracture and subsequent screw fixation. To accomplish this, we mechanically reproduced Type II and Type III odontoid fractures on isolated C2 vertebrae by varying the direction of load. These fractures were subsequently stabilized with a single 3.5 mm screw and retested for multidirectional stability and load to failure. Reduced and instrumented specimens were found to have a stiffness equivalent to one half of that of the unfractured odontoid. Load to failure was also slightly less than one half of the original fracture force (average 160 lb). Screw failure was by a cut-out mechanism in all Type III fractures and by bending of the screw in all Type III fractures. Our findings, in conjunction with the existing literature, strongly suggest that Type III fractures result from extension forces, whereas Type II fractures result from lateral or oblique loading forces. Single screw fixation of an odontoid fracture will provide stability equal to approximately one half that of the unfractured bone. PMID- 8441932 TI - The value of facet joint blocks in patient selection for lumbar fusion. AB - The purpose of this study was to ascertain the correlation between diagnostic facet blocks and treatment outcome, both surgical and nonsurgical. One hundred twenty-six patients who had previously undergone diagnostic facet injections were reviewed. Eighty-two had subsequently undergone lumbar arthrodesis. The rest were treated with a variety of nonoperative modalities. Statistical analysis of accumulated data failed to show any significant correlation between the results of facet blocks and outcome of operative arthrodesis. In addition, statistical analysis failed to show any significant correlation between the facet block results and the outcome of nonoperative treatment. The authors concluded that lumbar facet joint injections cannot be used to determine appropriate patient treatment because they are not predictive of either surgical of nonsurgical success. PMID- 8441933 TI - Spinal cord stimulation for the failed back syndrome. AB - Thirty-two patients with failed back syndrome received a trial of spinal cord stimulation. Stimulators were internalized in 26; long-term follow-up was available for 23 of these patients. Seventy-six percent of the 22 patients with stimulators still present at 1 year and 74% of the 19 patients with stimulators still present at 2 years were receiving 50% or better pain relief. Patients routinely underwent pain team evaluation and therapy, psychological testing and a transcutaneous electrical nerve stimulator trial prior to consideration of spinal cord stimulation. The most common complication was electrode migration. Spinal cord stimulation should be considered as an important therapeutic modality in carefully selected patients with failed back syndrome. PMID- 8441934 TI - Mechanics of anatomic reduction of thoracolumbar burst fractures. Comparison of distraction versus distraction plus lordosis, in the anatomic reduction of the thoracolumbar burst fracture. AB - The adequate reduction of vertebral burst fractures is dependent on successful application of distractive forces in combination with the restoration of normal spinal lordosis. However, the optimal sequence of distraction in comparison to distraction plus lordosis in the anatomic restoration of the fractured thoracolumbar spine has not been described. Burst fractures of the L1 vertebra were first created and the reduced in vitro using three differing reduction techniques. In six fresh human cadaver spine specimens, the mean fracture severity based on the degree of canal compromise was 31% (SD +/- 20%) after fracture. Reductions were performed using the AO Fixator Intern, the Reduction Fixation (RF) Device, and the Steffee plate systems following standard clinical techniques. The AO Fixator Intern provided independent but variable control of distraction and lordosis, the RF device provided variable distraction with independent, but preset, correction of lordosis and the Steffee system provided set distraction and stabilization. Both the AO and RF devices restored the lordosis (7.6 degrees +/- 5.2 degrees and 9.7 degrees +/- 4.5 degrees, respectively) better than the Steffee plate system (0 degrees +/- 1.6 degrees). However, the AO device provided poorest restoration of the posterior vertebral body height (92% vs 96% for the RF device and 99% for the Steffee plate). The RF device, which restored both lordosis and posterior vertebral body height to the near anatomic prefracture level, provided significantly better canal clearance (9% +/- 8%) than the other techniques, P < 0.05. The study demonstrates that instrumentation systems that provide independent correction of distraction and lordosis can best restore anatomic alignment, with indirect neurodecompression of the compromised spinal canal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441935 TI - Structural variation of the anterior and posterior anulus fibrosus in the development of human lumbar intervertebral disc. A risk factor for intervertebral disc rupture. AB - A morphologic comparison of the laminated structure of the anterior and posterior anulus fibrosus of lumbar intervertebral disc was made on 24 L3-4 and L4-5 discs obtained from 10 fetus, one child, and one young adult cadavers. Low power microscopic and polarized microscopic observations and measurements on the transverse sections were performed to assess 1) lamellar bundle arrangement, 2) number of distinct lamellar bundles, 3) percentage of incomplete lamellar bundles, and 4) fiber-interlacing angles. The number of lamellar bundles was greater in the anterior anulus than in the posterior anulus. A very complex structure was observed in the posterior middle anulus in all the specimens, with a high percentage of incomplete/discontinuous lamellar bundles and greater fiber interlacing angles. Loose connection of the lamellar bundles of posterior outer anulus was observed in fetal discs. The annular strength was not measured in the present study, however, the risk of posterior disc rupture in the young may be influenced by an inherent structural variation with a weak posterior anulus fibrosus. PMID- 8441936 TI - Magnetic resonance imaging analysis of percutaneous discectomy. A preliminary report. AB - Twenty-one consecutive patients (27 lumbar discs) were treated by percutaneous discectomy for lumbar herniated disc disease from July 1988 through March 1989. Twenty-six discs in 20 patients were evaluated with preoperative and postoperative magnetic resonance images graded by a neuroradiologist blinded to the clinical and prior imaging results. Fifteen patients were treated by one level percutaneous discectomy and six patients by two-level percutaneous discectomy. The disc herniations were graded with respect to size, type, location, and hydration status on the magnetic resonance image scans. The postoperative magnetic resonance images were obtained 2-6 months after percutaneous discectomy. Early clinical outcomes after percutaneous discectomy were compared with the various magnetic resonance imaging parameters. Overall, treatment for thirteen patients (62%) was considered clinically successful (decrease or elimination of pain) after percutaneous discectomy, whereas treatment for eight (38%) patients was considered to clinically fail (persistence of pain) with follow-up ranging from 1 to 6 months postoperatively. Three of the patients in whom treatment failed have been subsequently treated successfully by laminotomy and discectomy. On the average, there is a small absolute decrease (5% of the anteroposterior diameter of the spinal canal) in the size of disc herniations when treated by percutaneous discectomy. Although this study is limited by a small sample size and lacks statistical significance, it appears that an early clinical success after percutaneous discectomy may be related to a few magnetic resonance imaging parameters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441937 TI - An experimental study comparing percutaneous discectomy with chemonucleolysis. AB - The aim of this study was to assess the macroscopic and microscopic reaction of the intervertebral disc to discectomy with the Automated Nucleotome (Surgical Dynamics, San Leandro, CA), and to compare this with simple trephining of the annulus and with chemonucleolysis. In eight adult sheep, two of four adjacent lumbar discs were randomly incised using the trephine of the Automated Nucleotome, while the remaining levels underwent nuclear excision with the Automated Nucleotome probe. Another four sheep underwent chemonucleolysis at three adjacent lumbar levels. All animals were killed at 6 weeks. The discs that had undergone trephining alone and those treated with the Automated Nucleotome probe had almost identical radiographic and macroscopic changes and showed similarities on microscopic examination. Macroscopically, these discs did not differ from control levels, whereas those treated with chymopapain showed marked changes with a reduction of both nuclear and annular volume. The results of this study suggest that any therapeutic effect of percutaneous discectomy with the Automated Nucleotome is likely to be attributable to the perforation of the annulus alone with the removal of small amounts of nuclear material contributing little, or nothing, to the claimed benefits of the procedure. PMID- 8441938 TI - Nucleus pulposus regeneration after chemonucleolysis with chymopapain? AB - Chemonucleolysis was unsuccessful in 100 out of 519 patients with herniated lumbar discs treated within a period of 3 years. These patients were subsequently submitted to open surgery. Disc material from 88 of the 100 patients was examined by light microscopy (hematoxylin and eosin, van Gieson's, Nissl's and periodic acid-Schiff staining) to verify the effect of enzymatic activity compared to the histologic findings in a similar control group. In 84 of the 88 cases, signs of enzymatic activity were revealed by eosinophilia of the ground substance, altered Nissl staining and positive periodic acid-Schiff reaction within the chondrocyte halos. These alterations indicate that the enzyme was active and confirm the results of previous studies with smaller numbers of cases. Histologic alterations were quantified according to the intensity and extent of staining. The signs of enzymatic activity were significantly (P < 0.01) stronger after short time intervals between chemonucleolysis and surgery than after long intervals. These findings may be interpreted as indicating a regenerative potential of the nucleus pulposus. PMID- 8441939 TI - Optimal spinal strength normalization factors among male railroad workers. AB - In spite of increasing interest in techniques and devices for quantifying trunk strength and lifting capacity, relatively little research has been done to determine optimal normalizing factors for strength. The isolation of the ideal factors is a critical prerequisite for comparison of patient data to expected physical capacities in the uninjured population. In the present study, 160 incumbent railroad workers from four heavy laboring jobs were tested for isokinetic trunk strength and lumbar/cervical isokinetic lifting capacity as part of a study to establish normative data (Union Pacific RR, Omaha, NE). Three variables relating height and weight were studied to determine optimal normalization: actual body weight (BW), ideal weight (IW) and adjusted weight (AW). "IW" is actually a height/weight variable based on a weight control chart specifying ideal weights for given heights and genders. "AW" represents the lesser of BW or IW. Subjects were tested for isokinetic trunk extension/flexion for lumbar (floor-to-knuckle) and cervical (knuckle-to-shoulder) lifts. Results demonstrated that the isolated trunk strength tests showed the best correlation coefficients with BW for flexion-extension work at 60 and 150 per sec. Moreover, the correlation coefficients between the lumbar isokinetic lifting peak force measures and BW were high (ranging 0.49-0.67, P < 0.001), with much lower correlations for AW or IW. By contrast, cervical correlations between Liftask peak force and the height/weight variables were all lower, and were also better for AW than for BW or IW (ranging 0.37-0.50). It appears that body weight is the best normalizing factor for isokinetic trunk flexor/extensor strength and lumbar (floor-to-knuckle) lifting.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8441940 TI - Trunk strength and lumbar paraspinal muscle activity during isometric exercise in chronic low-back pain patients and controls. AB - The purpose of this study was to describe trunk strength and lumbar paraspinal muscle activity across five angles of flexion during isometric exercise and rest in chronic low-back pain patients and control subjects. High muscle tension as measured by surface integrated electromyography is predicted by a muscle spasm model, and low muscle tension is predicted by a muscle deficiency model. Prior lumbar surgery had no affect on peak torque or maximum surface integrated electromyography data. Both groups produced greater torque and less surface integrated electromyography in more flexed positions. Chronic low-back pain patients exhibited lower peak torque and lower maximum surface integrated electromyography bilaterally during isometric extension effort across all angles. A muscle deficiency model of chronic low back pain was supported by these data and a muscle spasm model was not supported. Discriminant analyses indicated that monitoring maximum surface integrated electromyography of lumbar muscles during isometric effort facilitates classification of chronic low-back pain patients. Future directions are discussed in terms of applying psychophysiologic methods to pain rehabilitation. PMID- 8441941 TI - Incomplete spinal cord evoked injury potential in man. AB - Intraoperative monitoring of spinal cord evoked potentials (SCEP) evoked by tibial nerve stimulation was performed in six patients who underwent junctional coagulation lesion of the dorsal root entry zone for relief of intractable pain. The pain was secondary to complete brachial plexus avulsion. Normal spinal cord evoked potentials showed an initial positive wave and two negative waves, then a group of high frequency conducted waves. On the avulsion side, incomplete spinal cord evoked injury potentials were recorded in all cases and in one on the normal side also. The incomplete spinal cord evoked injury potential consisted of a high amplitude positive wave with a sharp rising phase and slower falling phase that led to a long lasting, low-amplitude, negative deflection. Several high-frequency components were superimposed onto the monophasic positive wave. The duration of these superimposed components was approximately the same as the duration of the normal spinal cord evoked potentials, but the incomplete spinal cord evoked injury potentials were longer than normal spinal cord evoked potentials for the negative afterwave. Incomplete spinal cord evoked injury potential amplitude was 3-11 times higher than the normal spinal cord evoked potentials. Our results suggest two possible sources of incomplete spinal cord evoked injury potential: the chronic subclinical spinal cord injury produced by the avulsion and the effect of subpial placement of the recording electrodes. PMID- 8441942 TI - Incomplete neural deficits in thoracolumbar and lumbar spine fractures. Reliability of Frankel and Sunnybrook scales. AB - Because neural status is used both as a treatment determiner and outcome measure, a universal, reliable scale is required. Experienced personnel, provided with concise definitions, demonstrated high inter-rater reliability of Frankel and Sunnybrook scales (Pearson correlation coefficients 0.71-0.91), with 94-100% intra-rater agreement. Both scales correspond to total sensory and motor function but are insensitive to walking and bladder function. Frankel's wide clinical use, reliability, and simplicity identify it to be the preferred measurement system until a better alternative is developed. Discussion of neural status must include description of bladder and walking function. PMID- 8441943 TI - Immunohistochemical study of nerves in lumbar spine ligaments. AB - An indirect horseradish peroxidase immunohistochemical technique was used to identify neurofilaments protein-immunoreactive fibers in lumbar spine ligaments, from patients who underwent spinal surgery for disc herniation. Histologically, neural elements were abundant in all ligaments examined. In the ligamentum flavum the neurofilaments protein-immunoreactive nerve fibers were located especially close to blood vessels and fat globules. Bundles of nerve fibers were seen in all ligaments specimens except those from the ligamentum flavum. Supraspinous ligament and lumbodorsal fascia show also individual axons and free nerve endings. Contrary to the gold chloride impregnation method, immunohistochemical staining revealed no recognizable sensory corpuscles in these ligaments. This can be explained by the lack of immunoreaction of both the capsule of sensory corpuscles and the perineural sheaths of nerve fibers. PMID- 8441944 TI - Terms used for diagnosis by English speaking spine surgeons. PMID- 8441945 TI - Intraspinal therapy using methylprednisolone acetate. Twenty-three years of clinical controversy. AB - The intraspinal use of methylprednisolone acetate (Depo-Medrol, Upjohn Company, Kalamazoo MI) began in 1960, followed 10 years later by reports of complications. In 1960, methylprednisolone acetate was first injected by the epidural route to treat low-back syndromes. Then in 1961, the intrathecal route was more widely used to treat arachnoiditis and multiple sclerosis. Epidural therapy again came into general use in 1980 for the treatment of the failed-back syndrome because intrathecal therapy was virtually abandoned after 10 years of spirited scientific controversy. Epidural steroid therapy is now employed extensively, and there are many sanguine reports of its efficacy in treating chronic pain secondary to the failed-back syndrome, but there have also been reports of complications. This review was prompted by recent manufacturer warnings, as well as by an ongoing heated controversy in Australia regarding its use epidurally. During the last 30 years, one can define 5 instructive historical parallels between intrathecal and epidural steroid therapy, and this historicity points up several principles that should govern any further epidural therapy with methylprednisolone acetate. This critical chronologic review surveys neurosurgical use from 1960 to 1970, neurologic use from 1970 to 1980, and anesthesiology use from 1980 to present. PMID- 8441946 TI - The effect of lumbar disc surgery on postoperative pulmonary function and temperature. A comparison study of microsurgical lumbar discectomy with standard lumbar discectomy. AB - Preoperative and postoperative pulmonary function and body temperature were measured prospectively in 15 patients undergoing either microlumbar discectomy or standard lumbar laminectomy and discectomy for herniated nucleus pulposus. In these otherwise comparable groups patients undergoing standard lumbar laminectomy and discectomy had significant depression in pulmonary function in the first 20 hours postsurgery and febrile temperatures for as long as 48 hours postsurgery. No alteration in pulmonary function or body temperature was observed in those operated on by the microlumbar discectomy technique. We conclude that patients undergoing microlumbar discectomy for lumbar disc herniation have less postsurgical pulmonary morbidity and temperature elevation than those treated by lumbar laminectomy and discectomy. PMID- 8441947 TI - Lumbar spinal stenosis: clinical/radiologic therapeutic evaluation in 145 patients. Conservative treatment or surgical intervention? AB - In this prospective study, 145 patients with lumbar spinal stenosis were evaluated for clinical signs and radiologic findings and conservative treatment results. Clinical parameters such as pain on motion, lumbar range of motion, straight leg raising test, deep tendon reflexes, dermatomal sensations, motor functions and neurogenic claudication distances were assessed at admission and were compared after a conservative treatment program was completed. A conservative treatment program consisted of physical therapy (infrared heating, ultrasonic diathermy and active lumbar exercises) and salmon calcitonin. Pain on motion (100%), restriction of extension (77%), limited straight leg raising test (23%), neurogenic claudication (100%), dermatomal sensory impairment (47%), motor deficit (29%), and reflex deficit (40%) were observed in the patients. All aforementioned disturbances except reflex deficits improved by the conservative treatment and results were statistically significant. The authors conclude that this conservative treatment should be the treatment of choice in elderly patients and in those patients without clinical surgical indications. PMID- 8441948 TI - Acquired spinal stenosis secondary to an expanding thoracic vertebral hemangioma. AB - Intraosseous hemangioma is a slow-growing primary benign neoplasm of capillary, cavernous, or venous origin. The most common type is the cavernous hemangioma, composed of large thin-walled vessels and sinuses lined by endothelial cells. Although found in any bone, hemangioma is most common in the vertebrae, where it represents 2-3% of all radiographically detectable spinal tumors. Most spinal hemangiomas are solitary, asymptomatic lesions of the vertebral body, with 10-15% showing concomitant involvement of the posterior elements. Rarely, the lesion is located to the posterior arch. An unusual case of an expanding vertebral hemangioma isolated to the posterior elements of T9 is presented. PMID- 8441949 TI - Combined effects of compression and hypotension on nerve root function. A clinical case. AB - Previous animal experiments suggest that mild compression may increase susceptibility of nerve roots to the effects of hypotension. The authors report the case of a patient with an unstable L2 burst fracture whose motor skills and senses were intact. During fracture reduction and spinal distraction, sensory evoked potentials were recorded from the epidural space after right and left femoral and tibial nerve stimulation. Induced hypotension was used during the surgery. All responses were normal at the outset of the surgery. With hypotension, a marked drop in the amplitude of the right femoral evoked potential amplitude occurred; left femoral and both tibial responses remained unchanged. Evoked potential changes were reversible with reversal of hypotension. Postoperatively, the patient was neurologically intact. Further analysis revealed a significant correlation between the right femoral evoked potential amplitude and systolic blood pressure (r = 0.63, P < 0.005), whereas amplitudes of the other responses were not significantly correlated with systolic blood pressure. This report provides clinical evidence to support the hypothesis that hypotension and local compression exert additive adverse effects on nerve root function. PMID- 8441950 TI - Surgical treatment of a patient with spondylolytic spondylolisthesis associated with cerebral palsy. A case report. PMID- 8441951 TI - Odontoid fracture malunion with fixed atlantoaxial subluxation. PMID- 8441952 TI - Fuchs' heterochromic uveitis: an update. AB - The clinical description of Fuchs' heterochromic uveitis was made in 1906. The subject was first reviewed in 1973. This paper discusses contributions to the literature on Fuchs' heterochromic uveitis since 1973. The widening diagnostic criteria are discussed, as are new theories on etiology and pathogenesis. Investigative methods include light and electron microscopy, fluorescein angiography and immunology are described. Management problems, particularly relating to cataract and glaucoma, are discussed and in the light of such data, current indications for, modalities of, and complications of treatment, are presented. PMID- 8441953 TI - Optic disc pallor: a false localizing sign. AB - A 20-year-old pregnant woman was referred with bilateral mild visual acuity loss and optic disc pallor. Because of profound color vision deficits out of proportion to her acuity loss, an abnormality of the cone photoreceptors was suspected. An electroretinogram confirmed the diagnosis of a cone dystrophy and precluded further costly and invasive testing. Cone dystrophy should be considered in the differential diagnosis of any patient with bilateral, nonrefractive visual loss, especially if color vision is disproportionately affected, even with a normal retinal appearance and no significant family history. PMID- 8441954 TI - The role of abnormalities in the anticoagulant and fibrinolytic systems in retinal vascular occlusions. AB - The hemostatic mechanisms involve both an anticoagulant system to check the coagulation cascade and a fibrinolytic system to remove formed fibrin clots. Abnormalities of the hemostatic system or acquired abnormal hematological factors can produce a thrombophilic state which accounts for 15-28% of unexplained systemic vascular thrombosis in young patients. Similar abnormalities have recently been identified in some patients with retinal vascular occlusions. Screening of selected patients with retinal vascular occlusions may reveal additional ophthalmological patients with specific thrombotic syndromes. PMID- 8441955 TI - Initial treatment of glaucoma: surgery or medications. AB - Should surgery or medications be the initial therapy for primary open angle glaucoma? In this set of articles, Drs. Sherwood, Migdal, and Hitchings present evidence suggesting that filtration surgery provides better intraocular pressure control than does medical treatment, good (or better) visual field preservation, and visual acuity as good as that in medically treated fellow eyes. They also cite cost effectiveness, quality of life, and possible adverse effects of medical treatment on future surgery. Drs. Sharir and Zimmerman, on the other hand, favor initial medical therapy, questioning the validity of some reports on surgical results, citing the risks of complications, and noting recent and current progress in the development of antiglaucoma medications. Dr. Schultz' editorial evaluates both points of view, concluding that additional prospective randomized tests may be useful and that either approach may be a viable option, as long as it is individualized to each particular patient. PMID- 8441956 TI - Ophthalmic etymology. AB - The foregoing selection of terms is but a small component of our expansive current ophthalmic vocabulary. It serves, nonetheless, as an interesting example of the role played by other languages in the formation of today's ophthalmic lexicon. To the credit of our medical forefathers and their creativity, an awareness of the etymologic basis of the words which we used daily in ophthalmology can be both entertaining and enlightening. PMID- 8441957 TI - Barrett's esophagus. PMID- 8441958 TI - Total quality management and continuous quality improvement: an introduction for surgeons. PMID- 8441959 TI - The total quality process applied to the operating rooms and other clinical processes. PMID- 8441960 TI - Selective splenocaval shunt for bleeding portal hypertension: fifteen-year evaluation period. AB - BACKGROUND: Splenocaval shunts have been used in this hospital since 1974 as an alternative to the distal splenorenal shunt. This report will detail the long term results with this operation. METHODS: Thirty-three patients who were subjected to selective splenocaval shunts for treatment of hemorrhagic portal hypertension are reported. Mean age was 48.4 years. Twenty patients were women. Twenty-seven patients were in Child class A and six were in Child class B. RESULTS: There were five postoperative deaths. Two patients experienced rebleeding. One patient had shunt obstruction and one patient had severe clinical encephalopathy. Actuarial survival rate was 54.9% at 5 years and was 47.5% at 15 years. At the time of evaluation 12 patients were alive and well (shortest observation period, 2 months and longest observation period, 173 months). One of these patients has mild encephalopathy. CONCLUSIONS: Selective splenocaval shunts are a good alternative for treatment of hemorrhagic portal hypertension in patients with good liver function. PMID- 8441961 TI - Obturator hernia: a continuing diagnostic challenge. AB - BACKGROUND: The rare obturator hernia has a high incidence of potentially lethal complications. This report reviews this condition and stresses the dangers of unrecognized obturator hernia. METHODS: Thirteen patients with 14 obturator hernias were seen during a 5-year period. All the patients were emaciated and elderly, and 12 were women. They all had clinical features of small bowel obstruction. The classic Howship-Romberg sign was present in only three patients. The diagnosis was made before surgery in five patients. RESULTS: All hernial sacs contained small bowel. Ileum were present in 11 instances. Richter-type hernia was present in 10 cases. Bowel resection for gangrenous loop was required in seven instances. Apart from associated poor medical conditions, delay in presentation and operation also contributed to the high morbidity and mortality rates. Five patients (38.5%) had postoperative complications, and two patients (15.4%) died of chest infections. CONCLUSIONS: The need for awareness of the condition is stressed and the diagnosis of obturator hernia should be strongly suspected in a thin, elderly woman who has small bowel obstruction and no previous abdominal surgery. PMID- 8441962 TI - Aortic revascularization of orthotopic liver allografts: indications and long term follow-up. AB - BACKGROUND: Occasionally because of certain conditions that would imperil arterial supply to a hepatic graft, it is necessary to base the arterial supply on the aorta. METHODS: Twenty orthotopic liver transplants (OLTs) in 19 patients were performed with arterial revascularization based on the aorta (Ao-OLT). In two patients the donor celiac axis was anastomosed directly to the aorta and in 18 to a conduit anastomosed to either the supraceliac (n = 10) or infrarenal (n = 8) aorta. RESULTS: One thrombosis occurred 2 months after the placement of a supraceliac conduit in an adult patients, accounting for a cumulative 1-year hepatic artery patency rate of 91.7% +/- 8.0% for 16 grafts placed in 15 adults and 100% for four grafts placed in four children. In comparison, hepatic artery based transplantation was associated with a 1-year patency rate of 92.6% +/- 1.9% for 245 adults and 94.7% +/- 5.1% for 19 children (difference not significant compared with Ao-OLT). By logistic regression analysis, the only factor independently associated with hepatic artery thrombosis was retransplantation (1 year hepatic artery patency rate 85.7% +/- 5.9% [n = 38] for retransplants vs 93.9% +/- 1.7% for primary transplantation [n = 246]; p < 0.05). For retransplantation, Ao-OLT revascularizations were superior to those based on the hepatic artery (1-year patency rate 100% [n = 11] vs 79.9% +/- 8.1% [n = 27]; p < 0.05). CONCLUSIONS: Indications for Ao-OLT include poor hepatic arterial inflow, small or anomalous recipient hepatic arteries, friable or attenuated native hepatic arteries as may be present during retransplantation, and recipient age less than 1 year, especially those less than 15 kg or in whom the recipient artery is less than 3 mm in diameter. In these more precarious situations, Ao-OLT achieves patency rates similar to those of primary, uncomplicated OLT, is superior for retransplantation, and has technical advantages in the small pediatric liver recipient. PMID- 8441963 TI - Nonvascular emergencies presenting as ruptured abdominal aortic aneurysms. AB - BACKGROUND: Patients may present with signs and symptoms of ruptured abdominal aortic aneurysm (RAA) but actually have other diseases mimicking RAA. The outcome of these patients has not been reported. METHODS: During the past 10 years, 16 patients presumed to have RAAs were found at operation to have other diseases accounting for the symptoms. Fifteen patients (94%) had abdominal pain, 9 (56%) had a pulsatile abdominal mass, and 7 (44%) were hypotensive on presentation. RESULTS: Ten of the 16 patients had intact aortic aneurysms at surgery; there were no reliable physical signs or diagnostic tests that could discern between RAAs and intact aneurysms with other intraabdominal diseases. Eight patients (50%) died in the perioperative period, including four with widespread metastases, three with overwhelming sepsis, and one with an acute myocardial infarction. None of the 10 patients with aneurysms suffered RAA after emergency laparotomy. Exploratory laparotomy was necessary to treat underlying disease in nine patients and was probably harmful only to the patient with a myocardial infarction. Two survivors with aneurysms underwent successful staged repairs. CONCLUSIONS: Mistaken diagnoses in patients who are suspected of having RAAs on the basis of physical findings are relatively uncommon. Exploratory laparotomies are required to correct the primary disease in most of these misdiagnosed patients. Few die as a direct result of laparotomy; true iatrogenic catastrophes associated with mistaken diagnoses are distinctly uncommon. PMID- 8441964 TI - Parathyroid carcinoma: the relationship of nuclear DNA content to clinical outcome. AB - This article reports the use of flow cytometry to determine tumor nuclear DNA content and its correlations with clinical outcome in a series of patients with parathyroid carcinoma. Information concerning nine patients with parathyroid cancer (aged 25 to 88 years) was reviewed. Paraffin-embedded, formalin-fixed archival tissue was used to determine tumor DNA content flow cytometrically. Twenty-five operative procedures were performed in nine patients, including 11 parathyroidectomies, two wide local excisions, six central neck dissections, and four median sternotomies for resection of metastases. With flow cytometry used to determine a tumor DNA index, five patients had evidence of tumor aneuploidy; in two patients two aneuploid peaks were evident. The DNA index ranged from 0.7 (hypodiploid) to 1.92 (mean, 1.31). Follow-up ranged from 1 to 18 years. Four patients died. Five were alive 1 to 13 years after diagnosis of parathyroid disease. Four of the five patients with evidence of tumor aneuploidy had metastatic disease and died, and the fifth has had three local recurrences. The four patients with diploid tumors were alive and free of disease 1, 3, 4, and 8 years after the initial operation. It is concluded that in patients with clinically or pathologically demonstrated parathyroid cancer, flow cytometry may help differentiate those whose cancers are likely to behave indolently (diploid tumors) from those with tumors (aneuploid) more likely to behave aggressively by recurring locally or metastasizing. PMID- 8441965 TI - Biliary tract anomalies associated with intestinal malrotation in the adult. AB - Intestinal malrotation is a rare disorder typically beginning in childhood. In the adult it is an uncommon diagnosis, and it usually begins with bowel obstruction. It is a congenital anomaly only once reported to be associated with other gastrointestinal abnormalities in an adult. We reviewed all patients with intestinal malrotation at the Johns Hopkins Hospital during the past 7 years to determine the incidence of associated biliary tract anomalies. Eight adult patients were found to have complete malrotation of the gut. Four patients (50%) had an associated abnormality of the biliary tree. Two of four patients had a clinical presentation consistent with biliary tract disease rather than intestinal malrotation. Two patients underwent exploration; the gallbladder was found to arise from the left lobe of the liver. Two patients underwent exploration; in these patients the porta hepatic structures were anterior to the duodenum (complete anteroposterior portal hepatic malrotation). None of the biliary abnormalities were suspected before surgery. Malrotation was diagnosed before operation in only two of the eight patients. We conclude that intestinal malrotation is rare in the adult, and it can be associated with biliary tract anomalies or disease. In an adult with suspected intestinal malrotation and biliary tract disease, the surgeon should be aware of possible variable or abnormal extrahepatic choledochal anatomy. PMID- 8441966 TI - Prospective randomized study of routine intraoperative cholangiography during open cholecystectomy: long-term follow-up and multivariate analysis of predictors of choledocholithiasis. AB - A prospective randomized study was performed to assess the value of routine intraoperative cholangiography (IOC) during cholecystectomy for gallstone disease. Four hundred and fifty-seven consecutive patients were screened for the presence of 11 predefined clinical criteria assumed to indicate choledocholithiasis. Two hundred and eighty patients who had no positive criteria and in whom preoperative endoscopic retrograde cholangiography had not been performed were randomized at the operating table to the IOC or no-IOC group. Follow-up was performed 6 to 8 years after the operation with a questionnaire and by use of clinical, biochemical, and radiologic investigations as indicated. Multivariate analysis was used to identify independent predictors of choledocholithiasis and the combination of criteria having the best predictive ability. The frequency of common bile duct calculi at operation was significantly correlated with age and with all clinical criteria except recent or present pancreatitis. However, only serum bilirubin level, cystic duct diameter, demonstration of common bile duct calculi on preoperative imaging or intraoperative palpation, and age at operation were independent predictors of choledocholithiasis. The overall best subset of clinical indicators contained all criteria with the exception of pancreatitis and alkaline phosphatase level. Negative predictive ability of the set of criteria was 100% for patients up to 60 years of age and 97% for patients older than 60 years at the time of operation. No case of residual common bile duct calculi was present in the IOC and no-IOC groups at follow-up. Our data strongly support a policy of performing IOC during cholecystectomy only when clinical criteria suggest the presence of common bile duct abnormalities or to clarify ductal anatomy. PMID- 8441967 TI - Do recent advances in diagnosis and operative management improve the outcome of gallbladder carcinoma? AB - To study the effect of recent advances in diagnosis and operative management on survival of patients with gallbladder carcinoma, records of 26 patients who underwent resection between 1960 and 1978 (group 1) and 25 patients who underwent resection between 1979 and 1991 (group 2) were compared. The operative mortality rate was lower in group 2 (0%) than in group 1 (12%). The 5-year survival rate was higher in group 2 (60.8%) than in group 1 (30.4%; p < 0.01). Although preoperatively undiagnosed cases were not less in group 2 than in group 1, cases diagnosed with certainty before surgery were increased significantly and suspected cases of gallbladder carcinoma were decreased in group 2 (p < 0.05) as a result of recent advances in hepatobiliary imaging techniques. Twenty patients in group 2 (80%) and 13 in group 1 (50%) had tumors less than 30 mm in diameter (p < 0.05). Nine patients in group 2 (36%) had tumors at an early stage (tumors limited to mucosal or muscular layer), and only two (8%) in group 1 had early stage tumors (p < 0.05). The incidence of curative resection was higher in group 2 (76%) than in group 1 (27%; p < 0.001). Earlier diagnosis and a higher chance of curative resection, together with improved surgical techniques, may contribute to the better survival seen in the recent 12-year period. PMID- 8441968 TI - Multiple primary melanoma: incidence and risk factors in 283 patients. AB - To identify patients with melanoma at risk for a second primary lesion and to assess the prognostic relevance of multiple primary lesions, 7816 patients treated for malignant melanoma have been reviewed. Two to nine primary lesions were identified in 283 patients (3.6%): two lesions were identified in 82% of these 283 patients, three lesions in 11%, and four lesions in 3%. Sixty-four percent were metachronous. Among patients with melanoma, the 10-year actuarial risk of a second primary lesion was 5%; a third of that risk was expressed within 3 months of the initial diagnosis plus a subsequent risk of 0.38% per year. Risk factors for multiple primary lesions were family history of melanoma, thin primaries, male sex, Celtic complexion, and a history of another cancer. Patients with a family history of melanoma had a 14% risk of a second primary lesion during the first 10 years after diagnosis. By univariate and multivariate analyses, there was no survival disadvantage for patients with multiple primary lesions. After median follow-ups of 3.7 and 4.8 years, respectively, 51.7% and 50.5% of the groups with single and multiple primaries were disease free. Mortality rates were 31% and 25%, respectively. It is appropriate to base therapeutic decisions and prognostic evaluations on the specific risk factors of each individual lesion. Identification of patients at high risk for multiple primary lesions may permit early diagnosis and improved outcomes. PMID- 8441970 TI - Intrahepatic portosystemic vascular stents: a bridge to hepatic transplantation. AB - Refractory esophageal variceal hemorrhage (EVH) remains a formidable problem in patients awaiting liver transplantations. Transjugular intrahepatic portosystemic shunts (TIPS) have provided an alternative approach for managing EVH that may obviate the need for portosystemic shunt surgery. Experience with TIPS placement and subsequent successful hepatic transplantation in patients without previous portosystemic shunt surgery has not been previously reported. Two patients are reported who underwent TIPS placement and subsequent successful hepatic transplantation without previous portosystemic shunt surgery. This experience indicates that (1) TIPS can provide effective control of EVH for at least several weeks, (2) TIPS placement decreases portal hypertension, thus facilitating technical performance of the transplant procedure and minimizing blood loss, (3) TIPS may undergo vascular incorporation, thus requiring that they be accurately positioned so that the lengths of suprahepatic inferior vena cava and portal vein are not compromised at the time of transplantation, (4) TIPS thrombosis can be effectively treated and prolonged patency may be observed, and (5) deterioration in hepatic function and exacerbation of hepatic encephalopathy were not observed after TIPS placement. In summary, TIPS provide an attractive, effective means for managing refractory EVH in patients awaiting liver transplantation. PMID- 8441969 TI - Use of a novel bioartificial liver in a patient with acute liver insufficiency. AB - We have developed a bioartificial liver support system (BAL) using porcine hepatocytes attached to microcarriers and placed on the outer surface of hollow fibers. The BAL system was attached to a plasmapheresis device that was then used to treat the plasma of a patient with acute liver failure. Our aim was to test the efficacy and safety of this system after a single short treatment period. A patient with alcohol-induced, severe, acute liver failure manifested by coagulopathy, rising plasma ammonia level, and deteriorating mental status was studied. The procedure was well tolerated by the patient, who remained hemodynamically stable throughout the treatment period. A marked increase in coagulation factor V, VII, VIII, and IX activities, a decrease in serum ammonia level (120 to 32 mumol/L), a twofold increase in all serum amino acids except for aminobutyric acid, and an improvement in mental status were noted after a 6-hour treatment period. This preliminary report of the first use of this novel BAL system in conjunction with plasmapheresis appears promising. A clinical study is now in progress to prove its efficacy. PMID- 8441971 TI - Laparoscopic ligation of splenic artery aneurysm. AB - Efforts should be made to avoid splenectomy because host resistance is maintained by the spleen. We describe here a 50-year-old woman in whom laparoscopic ligation of a splenic artery aneurysm 3.0 cm in diameter was successfully performed, without major complications. Computed tomography performed 5 months later revealed no infarction in the spleen. For this patient with liver cirrhosis and cholelithiasis, laparoscopic cholecystectomy was performed at the same operation. Laparoscopic surgery is most feasible when the splenic artery is markedly tortuous and protrudes from the pancreas. PMID- 8441972 TI - Mycoplasma hominis in liver transplantation. PMID- 8441973 TI - [Law, ethics and medicine]. PMID- 8441974 TI - [HIV, nutrition and immune defence]. PMID- 8441975 TI - [Preventive health care]. PMID- 8441976 TI - [Breast milk as elixir of life]. PMID- 8441977 TI - [Breast feeding of premature infants]. AB - A study was conducted among 56 women in order to discover factors which might motivate them to breast-feed their premature infants. At three months of age, 54% of the infants were breast-fed. At six the figure was 29% and at nine months 25%. Low birth weight, low gestational age and the severity of neonatal complications were associated with short duration of lactation. If the mother smoked, the mean lactation period was three months compared with 5.5 months in a non-smoking mother, even if the child was critically ill. The lactation period was longer among mothers with a higher education. If the mother expressed milk more than five times a day the lactation period was likely to be long. The most frequent reason for cessation of milk production was declining volume of milk. Women who deliver prematurely should start to express breast milk preferably within the first days after delivery. Information and encouragement enhance milk yield and prolong the breast-feeding period. PMID- 8441978 TI - [Nutritional counseling to patients with HIV infection. Can nutritional intervention prevent, expose or relieve symptoms in HIV-positive persons?]. AB - Patients with HIV-infection often exhibit progressive loss of weight and poor nutritional status. The problems, which may appear during all stages of the HIV infection, may be explained by low intake of food or selected nutrients as a result of anorexia and eating problems, and by impaired gastro-intestinal function and increased metabolic rate following secondary to opportunistic infections or the HIV-infection itself. The extent of weight loss and depletion of body cell mass is discussed in relation to the possible effect on development of the disease and time of death in AIDS-patients. Compromising on nutritional status may have a negative effect on the outcome of treatment, and may lead to malnutrition-related immune depression and rates of infection. Nutrition issues are of vital importance to HIV-infected persons. Although nutrition does not promise of a "magic bullet", dietary counselling and nutritional intervention may prevent cachexia and alleviate some symptoms of the disease. PMID- 8441979 TI - [Anemia in 1-year old infants--still a problem?]. AB - The results of a retrospective study of routine measurement of haemoglobin at the examination of one-year-old children at Groland mother and child clinic during 1989-91 showed that 37% of the children had anaemia. There was no difference between immigrants and the European population. There was no correlation between anaemia and sex in either of the population groups. This may imply that routine haemoglobin measurement should be generally introduced as part of the regular control of one-year-old children. PMID- 8441980 TI - [Haemophilus influenzae infections in children]. AB - Haemophilus influenzae may cause serious infections, especially in small children. During the period 1980-90, 45 children with systemic H influenzae infections were admitted to the University Clinic, Tromso. 17 patients had epiglottitis in the same period, but are not included in this material. One of the four septicemia patients and two of the 35 children with meningitis died, giving an overall lethality of 4.8%. Five of the patients with meningitis experienced neurological sequelae (14% of the patients with meningitis). Two of the systemic isolates of H influenzae were resistant to ampicillin because of beta-lactamase production, but all the isolates were susceptible to chloramphenicol and 3rd generation cephalosporins. PMID- 8441981 TI - [Hereditary diseases and abnormalities as cause of death during the first 2 years of life among 7 groups of Oslo children. A comparison between Norwegian and Pakistani children]. AB - Perinatal and infant death are important indicators of community health. We examined the rate of stillbirth and death before the age of two years among 36,700 children with Norwegian and 2,750 children with Pakistani background. There was no difference in the rate of stillbirth and death during the second year of life, but a 2.5-3 times higher death rate during the first year of life among the Pakistani children, compared with the Norwegian children. When deaths due to single gene disorders and congenital malformations were excluded, the death rate during the first year of life was similar in the two groups. The Pakistani children had an 18 times higher death rate from autosomal recessive disorders and a ten times higher death rate from malformations of the central nervous system. The difference in death rate between the two groups was probably due to the high rate of consanguinity among the Pakistani parents. PMID- 8441982 TI - [Duplication of the small intestine. Unusual cause of abdominal pain]. AB - Duplications of the alimentary tract are rare. Since 1982 only three patients with such anomalies have been treated in the Department of Paediatric Surgery at the University Hospital in Trondheim, Norway. We describe the last patient treated, where duplication of the ileum was found upon laparotomy, performed because of exaggerated recurrent abdominal pain. Duplications may be found anywhere along the alimentary tract and diagnosis can be difficult. The duplications can be found upon laparotomy for suspected appendicitis or bowel obstruction. The condition may also be suspected upon antenatal ultrasonography and in the event of abdominal symptoms after birth. PMID- 8441983 TI - [Karyotyping of fetuses with developmental disorders. A 5-year material 1985-89]. AB - During the period 1985 to 1989 foetal chromosomal analysis was performed in 121 of 318 pregnant women with foetal malformations detected by ultrasound. There were six failures. The percentage of foetuses karyotyped for developmental disorders increased from 13% in 1985 to 62% in 1989. An abnormal chromosomal pattern was found in 28 (24%) of the foetus. The pregnancy was terminated in 86% of cases with abnormal karyotype. The corresponding number in the group with normal chromosomes was 51%. The authors discuss the malformations leading to karyotyping, the methods used for karyotyping, the results of these tests and the consequences for the pregnancies. PMID- 8441984 TI - [100 years of pediatrics in Norway. The history up to 1950]. AB - The first department of pediatrics in Norway was opened at Rikshospitalet (The National Hospital of Norway) in January 1893. This marked the start of pediatrics as an independent discipline and specialty in Norwegian medicine. Upon this centennial we present the history of the department (and of pediatrics in Norway) up to 1950. PMID- 8441985 TI - [Chief medical officers and preventive health care]. AB - A survey conducted among all Norwegian Chief Municipal Medical Officers, provided information about their formal role and involvement in health promotion work. Of the total respondents, 71% regularly attended meetings of the Municipal Board of Health and 32% attended meetings of the Building Council; 80% had authority to forward proposals to the Board of Health on matters of environmental health. On average, the Chief Municipal Medical Officers spent one-fifth of their working time on community health promotion activities. 80% of the respondents would have liked to spend more time on these activities. These officials should have a stronger formal position in the field of health promotion, and they themselves should give higher priority to health promotion work. PMID- 8441986 TI - [War and health in Angola. Review of a patient material]. AB - The present study compares morbidity and lethality in two cohorts of in-patients in a provincial hospital in Angola. The first cohort was recruited during a period of peace (1978/1980), while the second was recruited during a period of increased guerilla activity in the province (1988). In wartime, the total number of patients from distant areas decreased, but, the proportion of children increased. There was a marked increase in the number of diagnoses related to poverty (tuberculosis, measles, anaemia, malnutrition), as well as on increase in mortality within these diagnostic groups. Although the area around the hospital was not directly involved in heavy war, the study clearly reflects some of the impacts of war on the health of a population. PMID- 8441987 TI - [HELLP--another syndrome]. PMID- 8441988 TI - [The new insurance rules]. PMID- 8441989 TI - [Presentation of medical records in court]. PMID- 8441990 TI - [Shall we have unified hospital records?]. PMID- 8441991 TI - [Professional secrecy and research]. PMID- 8441992 TI - [To help]. PMID- 8441993 TI - [The disease phenomenon in the light of economic and political realities]. PMID- 8441994 TI - Glial-neuronal interactions: relevance to neurotoxic mechanisms. PMID- 8441995 TI - Synergistic induction of cytochrome P450 by ethanol and isopentanol in cultures of chick embryo and rat hepatocytes. AB - The purpose of this study was to investigate whether isopentanol, the most abundant higher chain alcohol in alcoholic beverages, contributes to induction of different forms of hepatic P450s associated with consumption of these beverages. We have previously reported that ethanol and isopentanol each induce P450 2H1/2 in cultured chick hepatocytes and that ethanol induced P450 2B1/2, as well as P450 2E, in cultured rat hepatocytes. Here we investigated the induction of P450 by isopentanol alone and in combination with ethanol in cultured chick and rat hepatocytes. The forms of induced P450 were identified both enzymatically and immunochemically. In cultured chick hepatocytes, both isopentanol and ethanol induced P450 2E, but combined treatment with these alcohols had no greater effect than treatment with ethanol alone. In cultured rat hepatocytes, isopentanol alone did not induce P450 2E or 2B1/2 and had no effect on the ethanol-mediated induction of P450 2E. However, isopentanol combined with ethanol caused a synergistic induction of P450 2B1/2 in cultured rat hepatocytes and an additive to synergistic induction of P450 2H1/2 in cultured chick hepatocytes. The levels of enzyme activities induced by the combined alcohol treatment approached those induced by potent barbiturates. The results suggest that the pentanols in alcoholic beverages may be responsible for a barbiturate-like induction of P450 in hepatocytes. PMID- 8441996 TI - Daunorubicin-induced cardiac injury in the rabbit: a role for daunorubicinol? AB - This study evaluated potential contributions of daunorubicin and its principle metabolite, daunorubicinol, to the cardiotoxicity of daunorubicin therapy. Daunorubicin (15 mg/kg) or placebo (normal saline) was administered by iv bolus to New Zealand white rabbits and 3 to 4 days later, hearts were removed to measure contractility (dF/dt), concentrations of daunorubicin and daunorubicinol, and evidence of oxidative stress on glutathione and glutathione peroxidase. Contractile function of isolated atria and papillary muscles was depressed (p < 0.05). Daunorubicinol exceeded daunorubicin concentration in the heart (p < 0.005) with a ratio of metabolite to parent drug of 26 in atrial and 32 in ventricular tissue. There was a significant correlation between peak plasma (r = 0.63; p < 0.05) or cardiac concentration (r = -0.78; p < 0.02) of daunorubicinol, but not daunorubicin, and depression of dF/dt in papillary muscles. In separate in vitro studies, daunorubicinol at a concentration (5.5 micrograms/g tissue or 10 microM) approximating that observed ex vivo in heart inhibited Ca2+ uptake into cardiac sarcoplasmic reticulum vesicles by 39 +/- 3%, whereas 10 microM daunorubicin (14-fold higher than actual ex vivo cardiac concentrations) did not demonstrate any detectable inhibition. Daunorubicin treatment failed to significantly alter concentrations of GSH or GSSG or activities of glutathione peroxidase in the heart. Thus, cardiac dysfunction observed 3 to 4 days after a single dose of daunorubicin did not clearly relate to oxidative stress, but was associated with a cardiac concentration of daunorubicinol that appeared sufficiently high to impair Ca2+ metabolism. PMID- 8441997 TI - Metabolic activation of tris(2,3-dibromopropyl)phosphate to reactive intermediates. I. Covalent binding and reactive metabolite formation in vitro. AB - Analogs of tris(2,3-dibromopropyl)phosphate (Tris-BP) either labeled at specific positions with carbon-14, phosphorus-32, or oxygen-18 or dual-labeled with both deuterium and tritium were used as metabolic probes to study the chemical and metabolic events in the bioactivation of Tris-BP to chemically reactive metabolites in liver microsomal preparations. Oxidation at the terminal (C-3) carbon atom of the propyl groups of Tris-BP yielded the direct-acting mutagen 2 bromoacrolein as the major metabolite that binds to DNA. Although this reactive metabolite also appears to bind to microsomal protein, the rate of binding of radiolabeled Tris-BP to protein is 15-20x greater than binding to DNA, and some metabolites that retain the phosphate group are bound. Studies with deuterated analogs of Tris-BP implicate oxidation at C-2 of the propyl group as a major pathway that leads to protein binding which is enhanced by phenobarbital pretreatment of rats. Moreover, investigations with 18O-Tris-BP and H2(18)O show that Bis-BP that is formed from oxidation of Tris-BP incorporates one atom of oxygen from water. Deuterium isotope studies suggest that most of the Bis-BP arises from initial oxidation at C-2. Taken together these studies indicate that P-450 oxidation of Tris-BP at C-2 of the propyl group yields a reactive alpha bromoketone metabolite of Tris-BP that can either alkylate proteins directly or be hydrolyzed to Bis-BP and an alpha-bromo-alpha'-hydroxyketone that can alkylate microsomal proteins. PMID- 8441998 TI - Metabolic activation of tris(2,3-dibromopropyl)phosphate to reactive intermediates. II. Covalent binding, reactive metabolite formation, and differential metabolite-specific DNA damage in vivo. AB - Analogs of tris(2,3-dibromopropyl)phosphate (Tris-BP) either labeled at specific positions with carbon-14 and phosphorus-32 or dual-labeled with both deuterium and tritium were administered to male Wistar rats at a nephrotoxic dose of 360 mumol/kg. The covalent binding of Tris-BP metabolites to hepatic, renal, and testicular proteins was determined after 9 and 24 hr, and plasma concentrations of bis(2,3-dibromopropyl)-phosphate (Bis-BP) formed metabolically from Tris-BP were measured at intervals throughout the initial 9-hr postdosing period. The covalent binding of 14C-Tris-BP metabolites in the kidney (2495 +/- 404 pmol/mg protein) was greater than that in the liver (476 +/- 123 pmol/mg protein) or testes (94 +/- 11 pmol/mg protein); the extent of renal covalent protein binding of Tris-BP metabolites was decreased by 82 and 84% when deuterium was substituted at carbon-2 and carbon-3, respectively. Substitution of Tris-BP with deuterium at carbon-2 or carbon-3 also decreased the mean area under the curve for Bis-BP plasma concentration by 48 and 57%, respectively. The mechanism of Tris-BP induced renal and hepatic DNA damage was evaluated in Wistar rats by an automated alkaline elution procedure after the administration of analogs of Tris-BP or Bis BP labeled at specific positions with deuterium. Renal DNA damage was decreased when Tris-BP was substituted with deuterium at either carbon-2 or carbon-3; the magnitude of the change correlated with both a decrease in the area under the Bis BP plasma curve and a decrease in renal covalent binding of Tris-BP metabolites for each of the deuterated analogs. In marked contrast, analogs of Bis-BP labeled with deuterium at carbon-2 or carbon-3 did not show a decrease in the severity of renal DNA damage compared to unlabeled Bis-BP. On the basis of these observations a metabolic scheme for hepatic P-450-mediated oxidation at either carbon-2 or carbon-3 of Tris-BP affording Bis-BP by two alternate pathways that are susceptible to primary deuterium kinetic isotope effects is proposed. The Tris-BP metabolite, Bis-BP, is subsequently metabolized to reactive intermediates that cause DNA damage and bind to kidney proteins in a mechanism independent of cytochrome P-450. PMID- 8441999 TI - Toxicokinetics and metabolism of aniline and 4-chloroaniline in medaka (Oryzias latipes). AB - The in vivo toxicokinetics and in vitro hepatic microsomal metabolism of [14C]aniline and [14C]4-chloroaniline in medaka (Oryzias latipes) were investigated to provide a basis upon which to interpret the toxicological responses of small aquarium fish to aniline derivatives. During static aqueous exposures of up to 320 min, parent equivalents failed to reach steady state and results from depuration studies clearly demonstrated biphasic elimination. Due to low elimination rates, 40 to 20% of absorbed aniline and 4-chloroaniline doses, respectively, remained within the fish through 330 min postexposure. Based on an analysis of excreted metabolites, N-acetylation was the dominant route of in vivo metabolism for 4-chloroaniline, with no indication of ring hydroxylation, while the evidence suggested that polar conjugates were the dominant in vivo aniline metabolites. The toxicokinetics and in vivo metabolism of both aniline and 4 chloroaniline were best described by a two-compartment model that was consistent with the assumption that metabolites of the parent amines were accumulating in the fish. In partial support of the hypothesis that these amines are being metabolically activated in medaka, N-hydroxylation of aniline and 4-chloraniline to phenylhydroxylamine and 4-chlorophenylhydroxylamine were quantified in hepatic microsomal preparations. PMID- 8442000 TI - In vitro ozone exposure increases release of arachidonic acid products from a human bronchial epithelial cell line. AB - Eicosanoids released after ozone exposure of a human bronchial epithelial cell line, BEAS-S6, were analyzed by high-pressure liquid chromatography (HPLC) of supernatants from exposed cells prelabeled with [3H]arachidonic acid. BEAS cells released thromboxane B2 (TxB2), prostaglandin E2 (PGE2), leukotriene C4 (LTC4), LTD4, LTE4, and 12-hydroxyheptadecatrienoic acid (HHT) after exposure to ozone at concentrations of 0.1, 0.25, 0.5, and 1.0 ppm. The eicosanoids were identified by coelution with authentic standards. The largest product from ozone-exposed BEAS cells was the most polar peak, designated Peak 1. Release of cyclooxygenase products such as TxB2, PGE2, and HHT was inhibited by acetylsalicylic acid. Peaks that migrated with authentic standards for LTB4, LTC4, and LTD4 were inhibited by the lipoxygenase inhibitor nordihydroguaiaretic acid. The leukotrienes LTB4 and LTC4/D4 could also be detected by immunoassay of concentrated peak fractions. Thus BEAS cells released eicosanoids from cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism following exposure to ozone. Airway epithelial cells may be an important source of eicosanoids following ozone stimulation in humans. PMID- 8442001 TI - Stimulation of human polymorphonuclear leukocytes by consecutive doses of quartz and interactions of quartz with fMLP. AB - The role of free intracellular calcium [Ca2+]i was studied in the production of reactive oxygen metabolites (ROM) by human polymorphonuclear leukocytes (PMNL) after a single or two repeated doses of quartz. The significance of [Ca2+]i in the production of ROM was also studied after a dose of quartz prior to, or after, a dose of formylmethionylleucylphenylalanine (fMLP). When the production of ROM and changes in [Ca2+]i were measured after repeated stimulations of cells, the cells were always washed between stimulations. A dose of quartz elevated [Ca2+]i in untreated and washed cells, whereas a second dose of quartz did not induce any further increase in [Ca2+]i. On the contrary, quartz stimulated ROM production after both one and two consecutive doses. fMLP alone elevated [Ca2+]i and increased the production of ROM. Quartz before fMLP did not modify fMLP-induced [Ca2+]i increase, but attenuated fMLP-induced ROM production. Quartz-induced elevation of [Ca2+]i was not affected by a prior dose of fMLP, but the production of ROM by quartz was greatly amplified by prior exposure of PMNL to fMLP. Thus, both quartz and fMLP increase the production of ROM by mechanisms in which [Ca2+]i may have a key role. Priming of PMNL with fMLP prior to quartz seems to amplify quartz-induced ROM production but not to affect [Ca2+]i. It is plausible that both [Ca2+]i-dependent and -independent mechanisms may account for quartz induced ROM production in PMNL. PMID- 8442003 TI - Effects of zinc on rat hepatoma HTC cells and primary cultured rat hepatocytes. AB - Responses to zinc, applied in concentrations ranging from 3 to 200 microM Zn2+, were investigated in rat hepatoma tissue culture (HTC) cells and in primary cultured rat hepatocytes. The uptake of 65Zn, total Zn levels, cellular viability, metallothionein (MT) levels, superoxide dismutase (SOD) activities, and glutathione (GSH) levels were measured. Exposure at 50-200 microM Zn for 24 hr resulted in up to fivefold increases in intracellular Zn accumulation in hepatocytes and up to twofold increases in rat HTC cells. Hepatocytes increased their MT levels from 80 to 230 pmol MT/mg cell protein, whereas MT levels in HTC cells did not significantly change with increasing Zn applications. SOD activities rapidly increased in both cell types for applied [Zn] > 25 microM, eventually reaching up to two to three times the control SOD values at 200 microM applied Zn concentrations. GSH levels in hepatocytes increased to twice the control values, but gradually declined again with applied Zn concentrations > 100 microM, the latter probably due to progressive increases in GSH efflux. Cell viability tests indicated differences between effects on cellular metabolism (ATP levels) and effects on cellular condition (LDH leakage, 42K influx). The ATP data suggest significant but comparable Zn effects on cellular metabolism in both cell types, notwithstanding the large differences in cellular Zn, MT, and GSH levels. At comparable cytosolic total Zn levels, hepatocytes appeared more effectively protected against intracellular Zn toxicity by elevated MT and GSH levels. However, if considered with respect to applied Zn concentrations, at 200 microM cellular viability (LDH leakage) was more affected in hepatocytes than in HTC cells, the latter probably due to progressive sequestering of zinc on intracellular Zn-complexing compounds (MT, GSH) and subsequent accumulation of zinc in hepatocytes, in contrast with the absence of excessive Zn uptake by HTC cells. The overall results indicate that synthesis of (protective) cellular compounds like MT or GSH, although rendering cells resistant to metals, may--at the same time--result in relatively strong accumulation of potentially toxic metals. PMID- 8442002 TI - Synergistic neurotoxic effects of styrene oxide and acrylamide: glutathione independent necrosis of cerebellar granule cells. AB - Conjugation with glutathione (GSH) is a mechanism of detoxification of acrylamide (ACR); hence, prior depletion of GSH might be expected to exacerbate ACR's neurotoxicity. GSH levels in female rats were reduced by ip administration of styrene oxide (SO; 250 mg/kg), diethylmaleate (DEM; 0.5 ml/kg), or 2 vinylpyridine (VP; 100 mg/kg) 1.5 or 2 hr prior to a single dose of ACR (100 mg/kg). The time course of GSH depletion following treatment with SO/ACR, DEM/ACR, or VP/ACR showed that all three regimens were equally effective in reducing GSH in liver, cerebellum, cerebral cortex, and hippocampus. GSH levels in the liver were reduced to 4-22% of control levels between 2 and 4 hr after treatment and to 38-57% of control levels in all brain regions between 4 and 8 hr. ACR alone (100 mg/kg) reduced both brain and liver GSH to about 60% of normal. The administration of a second dose of ACR (also 100 mg/kg) 12 hr later further depleted brain and liver GSH to 33% of control. Brains were examined 2, 4, 7, 14, and 30 days after treatment by light and electron microscopy. The administration of SO plus ACR (in either order) produced lesions consisting of pyknotic granule cells confined to the anterior portions of the cerebellum and some of the small neurons of lamina II and III of the cerebral cortex. Electron microscopy revealed condensation of the granule cell chromatin and dissolution of the cytoplasm with the formation of large pericellular spaces. The granule cell lesion was not produced when the time between SO and ACR injections was either 4 or 24 hr. No pathology was observed following treatment with DEM/ACR, VP/ACR, ACR/ACR, vehicle (peanut oil), SO, or ACR alone. It appears that the neurotoxicity in animals treated with SO plus ACR is not directly the result of reduced cellular GSH levels per se, but may involve other detoxification pathways of ACR and SO. PMID- 8442004 TI - Response of human CYP1-luciferase plasmids to 2,3,7,8-tetrachlorodibenzo-p-dioxin and polycyclic aromatic hydrocarbons. AB - The cytochrome P4501 gene family consists of two members, CYP1A1 and CYP1A2, that are induced by halogenated hydrocarbons and polycyclic aromatic hydrocarbons. The human CYP1 promoters and 5'-flanking sequences were cloned into luciferase expression vectors to develop cell lines that stably express luciferase activity in response to CYP1 gene induction. Plasmids were initially tested in transient transfection assays. Transient transfections resulted in high-level expression of luciferase by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) from both the CYP1 expression vectors, pLUC1A1 and pLUC1A2. In dose-response experiments, 10 nM TCDD caused a maximal induction of pLUC1A2-directed luciferase activity that was 10 fold over control. Maximal pLUC1A1-directed luciferase activity was 65-fold over control in cells treated with 10 nM TCDD. Stable integration of CYP1-luciferase neo plasmids, pL1A1N and pL1A2N, into the human hepatoma cell line, HepG2, was achieved by selection with G418. G418-resistant colonies were isolated for both pL1A1N and pL1A2N plasmids. The pL1A2N transfectants showed basal-level luciferase activity, but were nonresponsive to treatment with 10 nM TCDD. These results are in contrast to the observed induction of pLUC1A2-mediated luciferase expression in transient transfection experiments. Stable integration of the human CYP1A2 gene sequences appears to silence the transcriptional activation by TCDD. The pL1A1N transfectants showed inducible luciferase activity and one cell line, referred to as 101L, was used to establish dose-response relationships for TCDD and various polycyclic aromatic hydrocarbons. Maximal induction occurred after treatment with 100 nM TCDD, 10 microM 3-methylcholanthrene, 50 microM benz[a]anthracene, and 50 microM benzo[a]pyrene. These studies illustrate the use of the CYP1A1-luciferase cell line for the study of structure-activity relationships. PMID- 8442005 TI - Induction of peroxisomal beta-oxidation by nonsteroidal anti-inflammatory drugs. AB - Several chemical and pharmacologic agents have been identified as peroxisome proliferators in rodents. Most of these compounds contain a lipophilic backbone linked to an acid moiety, generally a carboxylate. Since ibuprofen and other nonsteroidal anti-inflammatory drugs share these structural characteristics, their effects on peroxisomal beta-oxidation were examined. Ibuprofen, flurbiprofen, and indomethacin caused dose-related increases in peroxisomal beta oxidation in cultured rat hepatocytes. The dose-response for ibuprofen and flurbiprofen was roughly equivalent to that of clofibric acid, whereas indomethacin was less active. Ibuprofen and flurbiprofen are arylpropionic acids, which are structurally similar to the aryloxyisobutyric acid clofibric acid. Indomethacin differs structurally in that the acid substitution is on an indole ring. This structural difference may be responsible for the difference in activity. Ibuprofen and clofibric acid were also compared in vivo following 2 week dietary administration to rats. Ibuprofen increased relative liver weight and peroxisomal beta-oxidation and reduced serum lipids. Clofibric acid was more active than ibuprofen in vivo, particularly with respect to induction of peroxisomal beta-oxidation (16.8-fold vs 3-fold, respectively). The difference in activity of the two compounds in vivo was not consistent with the results in vitro. The disparity in peroxisomal activity of ibuprofen in the two test systems may be related to pharmacokinetic factors which are not present in vitro. PMID- 8442006 TI - The correlation between urinary and liver taurine levels and between pre-dose urinary taurine and liver damage. AB - Analysis of data from several studies has shown that urinary taurine levels are highly significantly correlated with liver taurine concentration in control rats. Furthermore, urinary taurine levels measured before dosing with various hepatotoxic agents are significantly correlated with serum AST and ALT values measured after dosing with hepatotoxicants. That is, animals with low urinary taurine values and therefore low liver taurine concentrations tend to show greater hepatic damage. These data suggest that taurine may have a protective function in the liver. PMID- 8442007 TI - Effects of the antioxidant butylated hydroxyanisole on cytosolic free calcium concentration. AB - The effect of the antioxidant butylated hydroxyanisole on free intracellular calcium was investigated in rat cardiomyocytes, rat pituitary cells, human umbilical vein endothelial cells, granulocytes and BHK-cells. The effects of incubation time and butylated hydroxyanisole (BHA) concentrations were examined with respect to the extracellular calcium concentration. Butylated hydroxyanisole increased the free cytosolic calcium concentration in a dose- and time-dependent manner irrespective of the presence of extracellular calcium. Differences between all cell types were observed in the sequel of the re-uptake of the calcium ions released by BHA. Dependence on the concentration of extracellular calcium on the extent of sequestration was seen in rat pituitary cells and cardiomyocytes only. PMID- 8442008 TI - Teratogenicity and immunotoxicity of 3,3',4,4',5-pentachlorobiphenyl in C57BL/6 mice. AB - Administration of 3,3',4,4',5-pentachlorobiphenyl (pentaCB) to female C57BL/6 mice at doses from 130.5 to 522 micrograms/kg body weight resulted in the dose dependent formation of fetal cleft palate and hydronephrosis. The estimated relative potency of 3,3',4,4',5-pentaCB compared to 2,3,7,8-tetrachlorodibenzo-p dioxin (TCDD) was in the range of < 0.07-0.04. The immunotoxicity of 3,3',4,4',5 pentaCB and two structurally-related congeners, 3,3',4,4'-tetraCB and 3,3',4,4',5,5'-hexaCB, was investigated in male C57BL/6 mice by determining their suppression of the splenic plaque-forming cell response to sheep red blood cells. The potencies of these compounds relative to TCDD were determined from the ratios of their corresponding ED50 values and were 0.77-0.55 (3,3',4,4',5-pentaCB), 1.1 0.29 (3,3',4,4',5,5'-hexaCB) and 0.14-0.03 (3,3',4,4'-tetraCB). These results demonstrate that the immunosuppressive activities of the PCB congeners relative to TCDD were much higher than observed for many other TCDD-like responses in mice and other laboratory animals. PMID- 8442009 TI - Dose-dependent induction or depression of cysteine conjugate beta-lyase in rat kidney by N-acetyl-S-(1,2,3,4,4-pentachloro-1,3-butadienyl)-L-cysteine. AB - The influence of N-acetyl-S-(1,2,3,4,4-pentachloro-1,3-butadienyl)-L-cysteine (NAc-PCBD) on cysteine conjugate beta-lyase in female rat kidney has been examined. After a single, non-nephrotoxic dose of NAc-PCBD (3 mg/kg), cytosolic beta-lyase enzyme activity was increased 1.5 to 3-fold commensurate with a corresponding increase in enzyme protein levels as assessed by both Western blot and ELISA analyses. Using a cDNA probe for beta-lyase, this induction was found to be accompanied by an increase in the cognate mRNA. In contrast, a higher, nephrotoxic dose of NAc-PCBD (10 mg/kg) decreased all the above parameters. These effects appeared to be specific to the cytosolic form of the enzyme as no changes in kidney mitochondrial beta-lyase or enzyme protein levels were observed. Repeated dosing with the lower dose level (3 mg/kg) resulted in either no change, or in some instances, a reduction in the above parameters, suggesting an accumulation of the xenobiotic and a masking of the induction phenomenon. The molecular mechanisms underlying these observations are discussed in terms of the nephrotoxicity of halogenated xenobiotics. PMID- 8442010 TI - Protective elevations of glutathione and metallothionein in cadmium-exposed mesangial cells. AB - Exposure of cultured rat mesangial cells to CdCl2 caused a dose- and time dependent increase in intracellular glutathione that was significant at 0.5 microM and maximal at 1 microM Cd2+. The effect depended on glutathione synthesis and was masked by inhibiting synthesis with buthionine sulfoximine. The cells responded to slightly higher concentrations of Cd with a marked decrease in DNA synthesis, and reversible depletion of glutathione enhanced this sensitivity. Pre induction of the thiol-rich protein metallothionein with ZnCl2 afforded a degree of protection to the glutathione-depleted cells. We conclude that the Cd dependent elevation of glutathione in these cells may be protective at concentrations of Cd that can arise during acute environmental and occupational exposures. PMID- 8442012 TI - Hexavalent chromium produces DNA strand breakage but not unscheduled DNA synthesis at sub-cytotoxic concentrations in hepatocytes. AB - Rat hepatocytes were used to investigate the possible induction of unscheduled DNA synthesis (UDS) and the extent of DNA strand breaks induced by sodium dichromate (a representative chromium(VI) compound) and chromium acetate hydroxide (chromium(III)) in vitro. Cytotoxicity, measured using tetrazolium salt (MTT) reduction assay, was found at a much higher dose of chromium(III), (> 50 microM), compared to that of chromium(VI), (> 2.5 microM), in cultured hepatocytes over 20 h treatment at 37 degrees C. Chromium(VI), but not chromium(III), stimulated minimal UDS in hepatocytes at sub-cytotoxic concentrations. A positive UDS response was only observed at cytotoxic concentration. DNA strand breaks in hepatocytes were induced by chromium(VI) following incubation at 37 degrees C for 1 h at doses of 10, 20 and 40 microM sodium dichromate. The subsequent ligation of such strand breaks in hepatocytes treated with 40 microM chromium(VI) for 1 h at 37 degrees C was demonstrated. The majority of strand breaks was repaired within 30 min following removal of the chromate. In conclusion, chromate-induced DNA strand breakage, possibly involving the formation of oxygen radicals and lack of significant UDS have some analogy to those produced by ionizing radiation. PMID- 8442011 TI - Further study of effects of chelating agents on excretion of inorganic mercury in rats. AB - The effects of three chelating agents, N-benzyl-D-glucamine dithiocarbamate (BGD), 2,3-dimercaptopropanol (BAL) and D-penicillamine (D-PEN), on the excretion of mercury in rats exposed to mercuric chloride (HgCl2), the chemical forms of mercury compounds excreted in the bile and urine and the intestinal reabsorption of mercury compounds in the bile were studied. Rats were injected intraperitoneally with 203HgCl2 (300 micrograms Hg and 74 kBq of 203Hg/kg) and 24 h later, they were injected intraperitoneally with a chelating agent (a quarter of an LD50). The injection of the chelating agents significantly enhanced the biliary and urinary excretions of mercury. The enhancing effect of BGD on the excretions of mercury was almost the same as that of BAL and much larger than that of D-PEN. The major chemical form of mercury in the bile and urine of rats injected with BGD after HgCl2 treatment was Hg-BGD compounds. The chemical form of mercury in the bile and urine of rats injected with BAL after HgCl2 treatment was mainly Hg-GSH compound. The mercury after HgCl2 and D-PEN treatment was excreted mainly via the urine in the form of Hg-D-PEN compound. The intestinal reabsorption of mercury from the bile of rats injected with BGD or D-PEN was only 0.18% or 0.38% of the dose, respectively. The intestinal reabsorption of mercury from the bile of rats injected with BAL was 27.38% of the dose. It was suggested that the Hg-GSH compound excreted in the bile after HgCl2 and BAL treatment is partly degraded to Hg-cysteine (Cys) by the intestinal membranous enzymes and that the ligand of Hg-Cys is replaced by BAL in the bile, resulting in the effective reabsorption of Hg-BAL compound from the intestine. PMID- 8442013 TI - Influence of sodium lauryl sulphate on 2,4-dinitrochlorobenzene-induced lymph node activation. AB - The influence of the anionic surfactant sodium lauryl sulphate (SLS) on the ability of the contact allergen 2,4-dinitrochlorobenzene (DNCB) to provoke draining lymph node cell proliferative responses, a correlate of skin sensitizing potential, has been examined in mice. Topical application of 10% SLS with 0.1% DNCB caused a more vigorous proliferative response than did exposure to 0.1% DNCB alone. Lower concentrations (0.1% or 1%) of SLS were ineffective and 10% SLS failed to influence proliferative responses to higher concentrations (0.5% or 1%) of DNCB. Using an in vitro model for measurement of percutaneous absorption 10% SLS was shown not to increase the skin penetration of 0.1% DNCB. We therefore examined the influence of SLS on the accumulation of dendritic cells (DC) in lymph nodes draining the site of exposure, an important early event during the induction phase of skin sensitization. The frequency of DC in draining nodes was measured following topical application of SLS, DNCB or a combination of both. Epicutaneous exposure to 0.1% DNCB caused only a modest increase in the number of lymph node DC. However, 10% SLS or a mixture of 10% SLS with 0.1% DNCB each resulted in a significant elevation of DC numbers. It is proposed that SLS augments the skin sensitizing potential of sub-irritant concentrations of DNCB via an increase in the number of immunostimulatory DC which reach the draining nodes. PMID- 8442014 TI - Modulation of N-nitrosodiethylamine-induced hamster lung tumors by ozone. AB - Male Syrian Golden hamsters were treated with subcutaneous injections of N nitrosodiethylamine (DEN), 20 mg/kg, twice a week for 24 weeks. Half the animals were kept in filtered air and the other half was exposed continuously to an atmosphere of 0.8 ppm of ozone. After 6 months, no more DEN injections were given and all animals were kept in air until termination of the experiment at 7 months. It was found that the animals kept in ozone developed half as many peripheral lung tumors as did the animals kept in air; however, the difference was not statistically significant. Tumors of the trachea, bronchi, nasal cavity and liver developed with the same incidence whether the animals were exposed to ozone or not. It was concluded that ozone, an agent known to produce cell proliferation in the respiratory tract, does not enhance the development of tumors in the peripheral lung or in the nasal cavity of hamsters. PMID- 8442015 TI - Neonatal exposure to DDT induces increased susceptibility to pyrethroid (bioallethrin) exposure at adult age.--Changes in cholinergic muscarinic receptor and behavioural variables. AB - We have recently reported that DDT and the pyrethroid bioallethrin cause similar changes in the brain muscarinic cholinergic receptors (MAChR) and behavioural disturbances in the neonatal and adult mouse when given to neonatal mice during the peak of rapid brain growth. In the present study the interaction between neonatal and adult exposure to DDT and bioallethrin, respectively, is explored. Ten-day-old NMRI mice received a single low oral dose of DDT (0.5 mg/kg body wt). At adult age (5 months) the mice received bioallethrin 0.7 mg/kg body wt./day per os for 7 days. Mice used as controls received a 20% fat emulsion vehicle. The spontaneous behavioural tests revealed significant differences, both in mice treated neonatally with DDT and receiving bioallethrin as adults and in mice receiving the vehicle as neonates and bioallethrin as adults, compared with their corresponding controls. However, the behavioural changes developed in mutually opposite directions. Significant changes in MAChR, assayed in the P2 fraction of the cerebral cortex by using the muscarinic antagonist, quinuclidinyl benzilate ([3H]QNB) and agonist carbachol, was only observed in animals receiving DDT as neonates and bioallethrin as adults. The present study indicates an increased susceptibility in the cholinergic muscarinic receptors and a different behaviour reaction in animals already exposed to DDT (at a physiologically relevant dose), when again exposed to a similar neurotoxic agent as adults. PMID- 8442016 TI - Oxidative stress in mouse heart by antitumoral drugs: a comparative study of doxorubicin and mitoxantrone. AB - Doxorubicin and mitoxantrone were given to mice in a single dose of 15 mg/kg body wt (i.p.). 'In situ' heart spontaneous chemiluminescence, hydroperoxide-initiated chemiluminescence and TBARS were measured in heart homogenates of treated and control animals at 2-5 days after injection. Heart spontaneous emission (control value: 45 +/- 5 cps/cm2) was increased by 10-fold in doxorubicin-treated mice 4 days after administration, whereas mitoxantrone did not produce any significant change. Administration of doxorubicin produced increases of 50% in hydroperoxide initiated chemiluminescence and of 80% in TBARS levels 4 days after injection. Mitoxantrone did not induce significant changes in these parameters as compared with the controls. Cardiac reduced glutathione levels were not affected by mitoxantrone but were decreased (about 30%) by doxorubicin (control value: 0.98 +/- 0.08 mumol/g organ). Our data indicate that mitoxantrone does not induce an increase in the endogenous lipoperoxidation rate in heart tissue as doxorubicin does; this could contribute to the lower cardiotoxicity of mitoxantrone as compared with doxorubicin. PMID- 8442017 TI - Relative potency of chlorinated dibenzo-p-dioxins (CDDs) in acute, subchronic and chronic (carcinogenicity) toxicity studies: implications for risk assessment of chemical mixtures. AB - This paper shows that the relative toxic potency of four chlorinated dibenzo-p dioxins (CDDs) is similar in two species with different sensitivities (guinea pig, Sprague-Dawley rat). More importantly, it also demonstrates that the relative toxic potencies of these homologues are very similar for acute, subchronic and chronic dosing in the same species (rat). Furthermore, examination of different endpoints of toxicity (mortality, porphyria, carcinogenicity) suggests that the dose-responses for these diverse end-points after acute, subchronic, and chronic administration are very similar if not identical for tetra-CDD. Based on toxicokinetic and toxicodynamic considerations, a new, possibly generalizable rule (average tissue concentration x time = toxicity) is derived for CDDs. Implicit in the relative potency arguments of CDDs is the requirement of a practical threshold dose for all endpoints of toxicity including cancer. PMID- 8442018 TI - Influence of fatty acid anilides present in toxic oils on the metabolism of exogenous arachidonic acid in cultured human endothelial cells. AB - The effect of fatty acid anilides (FAA) on the exogenous arachidonic acid (AA) metabolism and toxicity of isolated human endothelial cells was studied to clarify their possible role in the etiology of toxic oil syndrome. Confluent cells were incubated with and without linoleic acid anilide (LAA), oleic acid anilide (OAA) and two unrelated samples for 2-24 h prior to the addition of [l 14C]AA alone or with calcium ionophore A-23187. The eicosanoids produced were analyzed by RP-HPLC. A dual stimulatory and inhibitory effect on the conversion of exogenous AA as a function of preincubation time with anilides (100 and 1000 microM) was observed. Treated cells significantly increased (1-3-fold) the production of the main cyclooxygenase-derived prostanoids (6-keto-PGF1 alpha and PGF2 alpha) formed by these cells, with a maximum stimulatory effect after 2-3 h, only when AA was used alone. However, afterwards a time- and dose-dependent decrease in prostanoid formation was observed with LAA (P < 0.05 at 24 h), either in the absence or presence of ionophore A-23187 in the incubation mixture. This inhibitory effect on cyclooxygenase was not observed with OAA, which still stimulate after 24 h of treatment. The changes in prostanoid synthesis were not followed with a parallel release in the lactate dehydrogenase activity in the medium (except with unrelated samples). Moreover, anilide treatment increased the appearance of cytosolic lipid droplets or vacuoles after 2 and 5 h of contact with LAA and OAA, respectively. From these results, it was suggested that anilides impair prostanoid synthesis in endothelial cells; their stimulatory effect could be explained by an unspecific effect on cell membrane, not related to cell toxicity and the inhibitory effect by an inhibition of the cyclooxygenase activity. These observations further contribute to our understanding of the possible role of anilides in the etiology of the toxic oil syndrome. PMID- 8442020 TI - Reduction of liver taurine in rats by beta-alanine treatment increases carbon tetrachloride toxicity. AB - Treatment of rats with beta-alanine increases the urinary taurine levels and markedly reduces the concentration of taurine in the liver. Dosing with carbon tetrachloride (CCl4) during treatment with beta-alanine results in a marked decrease in urinary taurine concomitant with a decrease in food intake. Treatment of animals with beta-alanine increases the hepatotoxicity of single doses of CCl4 as determined histologically and by measurement of serum alanine transaminase (ALT) and aspartate transaminase (AST) levels. Urinary creatine is also raised significantly after the administration of CCl4 in beta-alanine-treated animals. However, the accumulation of triglycerides (TRIG) in the liver caused by dosing with CCl4 was not influenced by beta-alanine treatment. The data suggest that liver taurine levels may be an important factor in determining the degree of CCl4 induced cellular necrosis but not hepatic triglyceride accumulation. PMID- 8442019 TI - Alterations in cytoskeletal protein sulfhydryls and cellular glutathione in cultured cells exposed to cadmium and nickel ions. AB - To understand the mechanisms of Cd2+ and Ni2+ cytotoxicity, we have studied the effects of these two metal ions on the organization of cytoskeletal elements, microtubules (MT) and microfilaments (MF), cytoskeletal protein sulfhydryls and cellular glutathione (GSH) in cultured 3T3 cells. At a metal ion dose that caused 95% inhibition of DNA synthesis, Cd2+ (10 microM, 16 h exposure) induced MT depolymerization whereas Ni2+ (2 mM, 20 h exposure) elicited MT aggregation and bundling. Under these conditions, Cd2+ and Ni2+ also caused MF aggregation and redistribution. Furthermore, exposure of cells to Cd2+ resulted in a dose dependent increase in cytoskeletal protein sulfhydryls and cellular GSH levels. In contrast, treatment of cells with Ni2+ resulted in a dose-dependent decrease in cytoskeletal protein sulfhydryls as well as cellular GSH content. Time course studies showed that cells exposed to 10 microM Cd2+ exhibited a biphasic response in regulating their cytoskeletal protein sulfhydryls and cellular GSH, e.g. an initial decrease followed by a steady recovery and overshooting upon prolonged incubation. However, restoration of cytoskeletal protein sulfhydryls occurred approximately 2 h after commencement of cellular GSH recovery in Cd(2+)-treated cells. These results suggest that cellular GSH may play an important role in regulating cytoskeletal protein sulfhydryls. On the other hand, decrease of cellular GSH induced by Ni2+ might facilitate oxidation of cytoskeletal protein sulfhydryls and formation of disulfide bonds between individual MT polymers which would favor MT aggregation in Ni(2+)-exposed cells. In addition, we also demonstrated that elevation of cellular GSH in Cd(2+)-treated cells probably resulted from new GSH synthesis. PMID- 8442021 TI - The effect of chlorinated paraffins on hepatic enzymes and thyroid hormones. AB - Male rats and mice were administered chlorinated paraffins (CPs) by daily gavage in corn oil for 14 days. Chlorowax 500C (short chain CP with 58% chlorination), Cereclor 56L (short chain CP with 56% chlorination) and Chlorparaffin 40G (medium chain CP with 40% chlorination) were the CPs studied at dose levels of 0, 10, 50, 100, 250, 500 and 1000 mg/kg for both rats and mice. The no effect levels for hepatic peroxisome proliferation for the above chemicals, as determined by the CN insensitive palmitoyl co-enzyme A beta-oxidation (PCO) assay, were calculated as 184, 600 and 473 mg/kg and 180, 120 and 252 mg/kg for rats and mice, respectively, whilst those for percent liver weight/body weight were calculated as 74, 51 and 31 mg/kg and 215, 70 and 426 mg/kg for rats and mice, respectively. The short chain CPs were more potent peroxisome proliferators than the medium chain CP, with the mouse proving to be more responsive than the rat. Rats administered the highest dose of CPs showed a depressed plasma thyroxine (T4) level, with a concomitant increase in the plasma concentrations of thyroid stimulating hormone (TSH). The decreased plasma T4 levels appeared to be the result of increased T4 glucuronidation. PMID- 8442022 TI - Transplantation of genetically altered hepatocytes using cell-polymer constructs. PMID- 8442023 TI - Neural transplants in Parkinson's disease. CPH Neural Transplantation Group. PMID- 8442024 TI - Transplantation of fetal liver stem cells into patients and into human fetuses, with induction of immunologic tolerance. PMID- 8442025 TI - Hepatocyte transplantation into spleen or solid supports: comparison of morphology, function, and proliferative response. PMID- 8442026 TI - Transplantation of allogeneic retinal pigment epithelium under the kidney capsule. PMID- 8442027 TI - Tissue-engineered growth of bone and cartilage. PMID- 8442028 TI - Allospecific suppressive effect of TcR-alpha beta +CD4-8- T cells in the livers of mice inoculated with allogeneic cells via the portal vein. PMID- 8442029 TI - Enalapril: safe and effective therapy for posttransplant erythrocytosis. PMID- 8442030 TI - Reversal of myocardial dysfunction following renal transplantation. PMID- 8442031 TI - National Transplantation Pregnancy Registry: analysis of pregnancy outcomes of female kidney recipients with relation to time interval from transplant to conception. PMID- 8442032 TI - Successful percutaneous treatment of ureteral stenosis after renal transplantation. PMID- 8442033 TI - Match prognostic index for predicting waiting time to renal transplantation. PMID- 8442034 TI - Prognostic factors of hemolytic uremic syndrome in renal allografts. PMID- 8442035 TI - HMGCoA reductase inhibitors lovastatin and simvastatin in the treatment of hypercholesterolemia after renal transplantation. PMID- 8442036 TI - Impact of obesity on renal transplantation. PMID- 8442037 TI - Effects of recombinant human growth hormone on graft function in renal transplanted children and adolescents: the three-year experience of a Belgian study group. PMID- 8442038 TI - Hypercoagulable state as a risk factor in transplantation. PMID- 8442039 TI - Comparative analysis of concurrent urine cytology and kidney aspirate in the rapid assessment of acute allograft dysfunction. PMID- 8442040 TI - Optimizing kidney perfusion with anti-CD45 monoclonal antibody. PMID- 8442041 TI - Impact of vesicoureteral reflux on graft survival in renal transplantation. PMID- 8442042 TI - Abnormal lipid and lipoprotein profiles following renal transplantation. PMID- 8442043 TI - Renal transplantation in elderly patients: survival and complications. PMID- 8442044 TI - Rapidly rising pretransplant hematocrit and hematocrit > or = 30% signal independent risks for delayed function and primary nonfunction in primary cadaveric renal transplantation. PMID- 8442046 TI - Hepatic lidocaine metabolism is useful in the selection of patients in need of liver transplantation. PMID- 8442045 TI - Liver transplantation in newborn liver failure: treatment for neonatal hemochromatosis. PMID- 8442047 TI - Liver transplantation in patients beyond age 60. PMID- 8442048 TI - Hepatic retransplantation: the Hannover experience of two decades. PMID- 8442049 TI - Safety and operative stress for donors in living-related partial liver transplantation. PMID- 8442050 TI - Liver transplantation in children from living-related donors. PMID- 8442051 TI - Results with percutaneous transjugular intrahepatic portosystemic stent-shunts for control of variceal hemorrhage in patients awaiting liver transplantation. PMID- 8442052 TI - Management of emergencies before and after liver transplantation by early total hepatectomy. PMID- 8442053 TI - Use of cryopreserved vein allogeneic homografts in liver transplantation. PMID- 8442054 TI - Hepatic artery reconstruction under microvascular surgery in partial liver transplantation from living donor. PMID- 8442055 TI - Partial hepatic resection following liver transplantation. PMID- 8442056 TI - Hepatic vein reconstruction in pediatric living donor liver transplantation: an overview of a series of 30 cases. PMID- 8442057 TI - Transplantation of small donor livers in adult recipients. PMID- 8442058 TI - Clinical outcome of ischemic-type biliary complications after liver transplantation. PMID- 8442059 TI - Capillarization of the hepatic sinusoid in failed liver grafts. PMID- 8442060 TI - Late graft loss after liver transplantation: a study of 434 consecutive patients. PMID- 8442061 TI - Early outcome of liver transplantation in patients with a history of spontaneous bacterial peritonitis. PMID- 8442062 TI - Assessment of prognosis in transplant candidates by use of the Pugh-MEGX score. PMID- 8442063 TI - Spontaneous portosystemic shunts in cirrhotics: implications for orthotopic liver transplantation. PMID- 8442064 TI - Liver transplantation for alcoholic cirrhosis--do they mix? PMID- 8442065 TI - Orthotopic liver transplantation for end-stage alcoholic liver disease. PMID- 8442066 TI - Results and cost of orthotopic liver transplantation for alcoholic cirrhosis. PMID- 8442067 TI - Report from the Pitt-UNOS Liver Transplant Registry. PMID- 8442068 TI - Risk/benefit ratio of perioperative OKT3 in cardiac transplantation. AB - This study shows that perioperative OKT3 provides no benefit in terms of the time of onset or frequency of rejection or patient survival. However, it does result in an increased incidence of infection, particularly CMV infection. Thus, the risk/benefit ratio of perioperative OKT3 does not appear favorable. However, a multicenter, randomized trial including a larger number of patients and longer patient follow-up will be required to definitively answer the question. PMID- 8442069 TI - Donor-transmitted bacterial infection in heart-lung transplantation. PMID- 8442070 TI - Comparison of hemodynamic outcome of patients with pulmonary hypertension after double-lung or heart-lung transplantation. PMID- 8442071 TI - Transplantation for pulmonary hypertension. PMID- 8442072 TI - High-affinity cytotoxic T lymphocytes in the graft of heart transplant patients with rejection. PMID- 8442073 TI - Airway complications after lung and heart-lung transplantation. PMID- 8442074 TI - Pathology of unused donor lungs. PMID- 8442075 TI - Late airway changes in rat lung allografts: chronic rejection is a causative factor. PMID- 8442076 TI - Atrioventricular orthotopic heart transplantation: a prospective randomised clinical trial in 60 consecutive patients. PMID- 8442077 TI - Coagulation disorders after reperfusion of pancreatic allografts. PMID- 8442078 TI - Pancreas transplantation with portal venous and enteric drainage eliminates hyperinsulinemia and reduces postoperative complications. PMID- 8442079 TI - Cystoenteric conversion after whole pancreaticoduodenal transplantation: indications, risk factors, and outcome. PMID- 8442080 TI - Pancreas transplantation in the uremic patient: a random trial of total pancreas with bladder drainage versus duct obstruction of segmental grafts. PMID- 8442081 TI - Should uremic diabetic patients who want a pancreas transplant receive a simultaneous cadaver kidney-pancreas transplant or a living related donor kidney first followed by cadaver pancreas transplant? PMID- 8442083 TI - Retrospective analysis of the role of pancreatic biopsy (open and transcystoscopic technique) in the management of solitary pancreas transplants. PMID- 8442082 TI - Defects in quantitative and qualitative beta-cell function following successful segmental pancreas transplantation. Danish-Swedish Study Group of Metabolic Effect of Pancreas Transplantation (DSSGMEPT). PMID- 8442084 TI - Biopsies from pancreas allografts at time of dysfunction: pathologic comparison of allografts which ultimately failed versus those which continued to function. PMID- 8442085 TI - Selective mesenteric lymphoid irradiation eliminates the effector cells of lethal graft-versus-host disease while protecting radiosensitive intestinal tissue. PMID- 8442086 TI - Immunosuppressive requirements for small bowel/liver transplantation. PMID- 8442087 TI - Use of spleen transplantation and cyclosporine A treatment to ameliorate survival after small bowel transplantation. PMID- 8442088 TI - Prolongation of canine intestinal allograft survival with RS-61443, cyclosporine, and prednisone. PMID- 8442089 TI - Altered cell trafficking of mesenteric lymphocytes after heterotopic small bowel transplantation using systemic venous drainage. PMID- 8442090 TI - Morphological monitoring of human small bowel allografts. PMID- 8442091 TI - Surgical techniques for intestinal transplantation in the mouse. PMID- 8442092 TI - Graft-versus-host disease in fully allogeneic small bowel transplantation: incidence of the disease and strain combinations. PMID- 8442093 TI - Cytokine storm of graft-versus-host disease: a critical effector role for interleukin-1. PMID- 8442094 TI - Cyclosporine-induced syngeneic graft-versus-host disease: recognition of self MHC class II antigens in vivo. PMID- 8442095 TI - Protection against graft-versus-host disease by large doses of donor CD4+ T cells: a novel approach to bone marrow transplantation. PMID- 8442097 TI - Influence of HLA-DPB1 disparity on the development of acute graft-versus-host disease following unrelated donor marrow transplantation. PMID- 8442096 TI - Selective inhibition of CD4 graft-versus-host activity in IL-2-treated mice. PMID- 8442098 TI - Crucial role of the third and fourth hypervariable regions of HLA-DPB1 allelic sequences in primary mixed-lymphocyte reaction: application in allogeneic bone marrow transplantation. PMID- 8442099 TI - Role of tumor necrosis factor alpha in acute graft-versus-host disease and complications following allogeneic bone marrow transplantation. PMID- 8442100 TI - Helper T-lymphocyte precursor frequencies predict risks of graft-versus-host disease in bone marrow transplantation. PMID- 8442101 TI - Role of the mixed lymphocyte culture reaction in predicting acute graft-versus host disease after marrow transplants from haploidentical and unrelated donors. PMID- 8442102 TI - Decreased transplant-related complications and improved leukemia-free survival in adults receiving methotrexate combined with cyclosporin compared with either agent alone for prevention of graft-versus-host disease. Advisory Committee of the International Bone Marrow Transplant Registry. PMID- 8442103 TI - Bone marrow transplantation with unrelated donors: HLA class II oligonucleotide typing as predictive of mixed lymphocyte culture reactivity. PMID- 8442105 TI - Graft-versus-host disease: liver morphology and pheno/genotypes of inflammatory cells and target cells in sex-mismatched allogeneic bone marrow transplant patients. PMID- 8442104 TI - Effect of natural killer cell depletion on long-term multilineage allogeneic bone marrow engraftment. PMID- 8442106 TI - Unrelated donor matching for bone marrow transplantation. AB - We found that in our laboratory the MLC was interpretable in most cases, in spite of patient disease state and shipping blood from unrelated donors over great distances. Our data clearly show that DRB1 allele typing was a good predictor of MLC reactivity and we believe that MLC testing in DRB1 allele mismatched unrelated pairs is not informative. However, our data suggest that MLC testing in DRB1 allele matched unrelated pairs is informative, because many such pairs produced weak but significant allostimulation. These weak MLC reactions may guide improvements in matching unrelated donors for BMT. For example, our MLC data suggest that it is important to match unrelated donors at DRB3 alleles for BMT. PMID- 8442107 TI - Natural killer defined haplotypes are associated with particular ancestral haplotypes: implications for bone marrow transplantation. PMID- 8442108 TI - Protection against autoimmune diabetes by induction of mixed bone marrow chimerism. PMID- 8442109 TI - Chemotherapy versus allogeneic bone marrow transplantation in adults with acute lymphoblastic leukemia. PMID- 8442110 TI - Immunohematopoietic reconstitution by allogeneic and autologous bone marrow grafts as a means for induction of specific unresponsiveness to donor-specific allografts and modified self in autoimmune disorders. PMID- 8442111 TI - Major histocompatibility complex influences the development of acute graft-versus host disease in MHC-matched adult allogeneic bone marrow transplantation. PMID- 8442112 TI - Impaired B-cell tolerance in complete as compared with mixed chimeras after allogeneic bone marrow transplantation. PMID- 8442113 TI - Cross species graft-versus-host disease induces hepatic injury in association with a donor-derived cellular immune response. PMID- 8442114 TI - Summation of the biologic aspects of the congress. PMID- 8442115 TI - Superior long-term kidney graft survival in patients on maintenance immunosuppression with cyclosporine and azathioprine. PMID- 8442117 TI - Impact of the addition of a pancreas to quality of life in uremic diabetic recipients of kidney transplants. PMID- 8442116 TI - Correlation of preoperative renal function and identification of risk factors for eventual native renal failure in cyclosporine-treated nonuremic diabetic recipient of pancreas transplants alone. PMID- 8442118 TI - Patient rehabilitation following lung and heart-lung transplantation. PMID- 8442119 TI - Combined pancreas-kidney transplantation versus kidney transplantation alone: analysis of benefit and risk. PMID- 8442120 TI - Influence of pregnancy on kidney graft function. PMID- 8442121 TI - Influence of multiple factors (age, transplant number, recipient category, donor source) on outcome of pancreas transplantation at one institution. PMID- 8442122 TI - Improvement in autonomic function following pancreas-kidney versus kidney-alone transplantation. PMID- 8442123 TI - How "death with function" should be considered when calculating renal transplant outcome. PMID- 8442124 TI - Reversal of microangiopathy in long-term diabetic patients after successful simultaneous pancreas-kidney transplants. PMID- 8442125 TI - Pancreatic graft protects a simultaneously transplanted kidney from developing diabetic nephropathy: a 1- to 6-year follow-up study. PMID- 8442126 TI - Modelling long-term survival in 52,315 first cadaveric grafts: the European experience. PMID- 8442127 TI - Effect of center size and patient-mix covariates on transplant center-specific patient and graft survival in the United States. PMID- 8442128 TI - Morbidity, mortality, and long-term allograft function in kidney transplantation alone and simultaneous pancreas-kidney in diabetic patients. PMID- 8442130 TI - Adaptation and long-term function of transplanted kidneys in children. PMID- 8442129 TI - One-hundred and five cadaveric kidney transplants with cyclosporine in recipients more than 60 years of age. PMID- 8442131 TI - Long-term follow-up after heart transplantation in Chagas' disease. PMID- 8442132 TI - One thousand years of continuous function in 49 renal transplant recipients: clinical, renal, and immunologic features of 20-year successes. PMID- 8442133 TI - Characteristics of long-term survivors (> 20 years) after kidney transplantation. PMID- 8442134 TI - Status of long-term (25 years) survival of kidney transplant patients. PMID- 8442135 TI - Renal transplantation and intestinal urinary diversion: a 10-year experience. PMID- 8442136 TI - Causes of late graft failure in cadaveric renal transplantation. PMID- 8442137 TI - Life survival and transplanted kidney survival after pancreas transplantation in uremic diabetic patients. PMID- 8442138 TI - Treatment of recurrent focal segmental glomerulosclerosis with high-dose cyclosporine A and plasmapheresis. PMID- 8442140 TI - Long-term passive immunoprophylaxis of B virus recurrence after liver transplantation in HBs antigen-positive patients. PMID- 8442139 TI - Allograft biopsies in situ hybridization HBVDNA detection of serum HBs Ag repositive patients treated with anti-HBV immunoprophylaxis after liver transplantation for HBV cirrhosis. PMID- 8442141 TI - Should abdominal cluster transplantation be abandoned? PMID- 8442142 TI - Thrombospondin and the expression of adhesion molecules in acute and chronic renal transplant rejection. PMID- 8442143 TI - Anti-interleukin 2 monoclonal antibody following simultaneous pancreatic and kidney transplantation: a randomized trial vs rabbit antithymocyte globulin. PMID- 8442144 TI - Simultaneous pancreatic and kidney transplantation before end-stage chronic renal failure. PMID- 8442145 TI - Employment and disability after renal transplantation. PMID- 8442146 TI - Focal rejection: a cause of false-negative biopsy results? PMID- 8442147 TI - Evidence that active suppression contributes to the success of H-2-incompatible orthotopic corneal allografts in mice. PMID- 8442148 TI - Effects of renal transplantation on apoproteins: decrease in the B/A1 ratio atherogenicity index. PMID- 8442149 TI - Effect of immunosuppression on preexisting cancers. PMID- 8442150 TI - De novo malignancy emerges as a major cause of morbidity and late failure in renal transplantation. PMID- 8442151 TI - Oncogene-derived peptides: a new class of tumor rejection antigens? PMID- 8442152 TI - Malignancies under cyclosporine after kidney transplantation: analysis of a 10 year period. PMID- 8442153 TI - De novo malignancy following liver transplantation: a single-center study. PMID- 8442154 TI - Posttransplant lymphoproliferative disorders in liver recipients treated with OKT3 or ALG induction immunosuppression. PMID- 8442155 TI - Kaposi's sarcoma in renal transplant recipients: a report on 26 cases from a single institution. PMID- 8442156 TI - Long-term outcome of hepatitis B after renal transplantation during childhood. PMID- 8442157 TI - Impact of hepatitis B or C infection on the practice of kidney transplantation in the United States. PMID- 8442158 TI - Use of low-risk HCV-positive donors for kidney transplantation. PMID- 8442159 TI - Impact asymptomatic HIV-1 infection on renal allograft recipients. PMID- 8442160 TI - Kidney transplantations with HBsAg+ donors. PMID- 8442161 TI - Risk of AIDS (HIV) transmission in 581 renal transplants. PMID- 8442162 TI - Corynebacterium urealyticum: a new and threatening pathogen for the renal transplant patient. PMID- 8442164 TI - Cardiopulmonary bypass and profound hypothermia as a means for obtaining kidney grafts from irreversible cardiac arrest donors: cooling technique. PMID- 8442163 TI - Prophylactic use of liposomal amphotericin B (AmBisome) against fungal infections: a randomized trial in bone marrow transplant recipients. PMID- 8442165 TI - In situ perfusion of kidneys from non-heart-beating donors: the Maastricht protocol. PMID- 8442166 TI - Renal harvesting after in situ cooling by intra-aortic double-balloon catheter. PMID- 8442167 TI - Technical aspects of organ procurement from the non-heart-beating cadaver donor for clinical transplantation. PMID- 8442168 TI - Is warm ischemia the main limiting factor in the use of non-heart-beating donors in renal transplantation? PMID- 8442169 TI - Use of kidneys from marginal and non-heart-beating donors: warm ischemia per se is not the most detrimental factor. PMID- 8442170 TI - Update of our experience in long-term renal function of kidneys transplanted from non-heart-beating cadaver donors. PMID- 8442171 TI - Effect of combination in situ cooling and machine perfusion preservation on non heart-beating donor kidney procurement. PMID- 8442172 TI - Acute vascular rejection with hemolytic uremic syndrome in kidneys from non-heart beating donors: associated with secondary grafts and early cyclosporine treatment? PMID- 8442173 TI - Long-term follow-up of transplanted non-heart-beating donor kidneys: preliminary results of a retrospective study. PMID- 8442174 TI - Exploration of the system for cadaver kidney transplantation with the non-heart beating donor: efficacy of in situ cooling and low-dose cyclosporine. AB - To expand the indication for the cadaveric kidney donor, the reduction of prolonged warm ischemic damage is the most important factor. We believe that the restriction of warm ischemic damage will be decreased by using the ISC procedure and low-dose CyA regimen. PMID- 8442175 TI - Comparative study of the use of systolic and asystolic kidney donors between 1988 and 1991. The South Thames Transplant Group. PMID- 8442176 TI - Transplantation of kidneys from zero haplotype-matched living donors and from distantly related and unrelated donors in the cyclosporine era. PMID- 8442177 TI - Living unrelated kidney donation: an underutilized resource? PMID- 8442178 TI - Improved cardiac transplant survival with thyroxine treatment of hemodynamically unstable donors: 95.2% graft survival at 6 and 30 months. PMID- 8442179 TI - Impact of glycogen content of the donor liver in clinical liver transplantation. PMID- 8442181 TI - Estimates of organ-specific donor availability for the United States. PMID- 8442180 TI - Effluent levels of hyaluronic acid can predict ultimate graft outcome after clinical liver transplantation: a prospective series. PMID- 8442182 TI - Effects of cold ischemia time on cadaver renal allografts. PMID- 8442183 TI - Preliminary experience with a new liver allocation system within Eurotransplant. PMID- 8442184 TI - Utilization of available paediatric donor livers in the United Kingdom. PMID- 8442185 TI - Triiodothyronine treatment is not indicated in brain-dead multiorgan donors: a controlled study. PMID- 8442186 TI - Kidneys from cadaveric donors over 60 years of age. PMID- 8442187 TI - Liver transplantation from elderly donors. PMID- 8442188 TI - Impaired initial function in liver grafts from donors > 50 years of age. PMID- 8442189 TI - 94 consecutive living unrelated kidney transplants: 8-year graft and patient actuarial survival. PMID- 8442190 TI - Outcome of 1128 proposals for liver donation from brain-dead patients: a 1-year prospective study in Paris centers. PMID- 8442191 TI - Measurement of the potential for cadaveric organ retrieval in New South Wales, Australia. PMID- 8442192 TI - Transplantation of the extreme age donor kidneys. PMID- 8442193 TI - Outcome of cadaver kidneys using nonideal donors. PMID- 8442194 TI - Is it safe to liberalize donor criteria to include those over age 60 and those weighing over 90 kg? PMID- 8442195 TI - Renal transplantation in highly sensitized patients using the regional organ procurement crossmatch tray: the SEOPF kidney sharing system experience. PMID- 8442196 TI - Carolina rinse solution decreases liver injury during clinical liver transplantation. PMID- 8442197 TI - Simple cold storage of the heart with the University of Wisconsin solution: evaluation in canine heterotopically and orthotopically transplanted heart. PMID- 8442198 TI - Current status of the Eurotransplant randomized multicenter study comparing kidney graft preservation with histidine-tryptophan-ketogluterate, University of Wisconsin, and Euro-Collins solutions. The HTK Study Group. PMID- 8442199 TI - Kidney preservation with University of Wisconsin or Euro-Collins solution? An economic analysis. PMID- 8442200 TI - Canine and cadaver kidney preservation with sodium lactobionate sucrose solution. PMID- 8442201 TI - Disturbance of microcirculation associated with prolonged preservation of dog livers under University of Wisconsin solution. PMID- 8442202 TI - Endothelial cell kinetics after anoxia and hypothermia in preservation solutions as indicators of endothelial repair. PMID- 8442203 TI - Twenty-four-hour preservation of canine pancreas allografts using low-cost, low viscosity, modified University of Wisconsin cold storage solution. PMID- 8442204 TI - Successful 12-hour lung preservation with trehalose. PMID- 8442205 TI - Efficacy of University of Wisconsin solution for canine lung preservation. PMID- 8442206 TI - Comparison of University of Wisconsin and Stanford solution for heart preservation: coronary flow reserve in the posttransplant myocardium. PMID- 8442207 TI - Effects of abdominal en bloc procurement and of a high sodium preservation solution in liver transplantation. PMID- 8442208 TI - Importance of rinse solution vs preservation solution in prevention of microcirculatory damage after liver transplantation in the rat. PMID- 8442209 TI - Clinical study of crystalloid cardioplegia vs aspartate-enriched cardioplegia plus warm reperfusion for donor heart preservation. PMID- 8442210 TI - Preservation of small bowel with University of Wisconsin and Euro-Collins solution. PMID- 8442211 TI - Relative advantages of nondepolarizing solution to depolarizing University of Wisconsin solution in donor heart preservation. PMID- 8442212 TI - Sodium lactobionate sucrose solution for canine liver and kidney preservation. AB - With 24-hour preservation of canine liver, SLS solution showed inferior animal survival to UW solution. The lactobionate, raffinose, glutathione, and hydroxyethyl starch in UW solution have been shown to be important for liver preservation. However, our results suggest that sucrose should not be substituted for raffinose for the preservation of livers. In contrast to the liver, SLS solution performed the same or even better than UW solution for kidney preservation. The substitution of sucrose for raffinose, along with the addition of CPZ has either no effect or a slightly positive effect on kidney preservation. In conclusion, SLS solution may be a suitable solution for preserving canine kidneys, but is not suitable for liver preservation. These findings suggest that future development of preservation solutions should be focused on the needs of specific organs and not toward a generic, all encompassing preservation solution. PMID- 8442213 TI - Ultrastructural correlates of liver graft failure from storage injury: studies of graft protection by Carolina rinse solution and pentoxifylline. PMID- 8442214 TI - Improved myocardial preservation by modification of the University of Wisconsin solution with 2,3-butanedione monoxime and calcium. PMID- 8442215 TI - Effect of thromboxane A2 synthesis inhibitor OKY046 on canine pancreas and kidney preservation. PMID- 8442216 TI - Prolonged kidney preservation by inhibition of arachidonic acid metabolism. PMID- 8442217 TI - Inhibition of tumor necrosis factor release from cultured rat Kupffer cells by agents that reduce graft failure from storage injury. PMID- 8442218 TI - Effect of glutathione and glycine in kidney preservation. PMID- 8442219 TI - Microcirculatory effects of adenosine in rinse solution for liver transplantation in the rat. PMID- 8442220 TI - Functional integrity of vascular endothelium correlates with myocardial function in stored rabbit hearts. PMID- 8442221 TI - Successful 7-day perfusion preservation of the canine kidney. PMID- 8442222 TI - Prolonged ischemic times in pediatric heart transplantation: early and late results. PMID- 8442223 TI - Graft function, airway healing, rejection, and survival in pulmonary transplantation are not affected by graft ischemia in excess of 5 hours. PMID- 8442224 TI - Biliary complications after prolonged University of Wisconsin preservation of liver allografts. PMID- 8442225 TI - Limits of the MEGX test in the selection of liver grafts for transplantation. PMID- 8442226 TI - Safe use of liver donors with MEGX values less than 90 ng/mL. PMID- 8442227 TI - Assessment of viability of hepatic cell membrane after cold storage by 31P-NMR and 23Na-NMR spectroscopy. PMID- 8442228 TI - Malfunction of the liver after transplantation: an analysis of potential risk factors. PMID- 8442229 TI - Histological comparison of donor livers and lidocaine metabolism in the utilization of organs for liver transplantation. PMID- 8442230 TI - Study of the toxicity of various concentrations of 2-3-butanediol in the isolated perfused rat liver. PMID- 8442231 TI - Comparison of cold and warm ischemic injury in hepatocytes from the rat liver. PMID- 8442232 TI - Heat shock and recovery protects renal allografts from warm ischemic injury and enhances HSP72 production. PMID- 8442233 TI - Importance of protection of cold-stored small intestine against oxygen free radical-induced injury during the initial period of reperfusion. PMID- 8442234 TI - Lipid peroxidation of parenchymal and nonparenchymal hepatocytes during cold preservation and after reoxygenation in rats. PMID- 8442235 TI - Role of xanthine-oxidase system in mucosal injury after intestinal preservation and transplantation. PMID- 8442236 TI - Cadaveric kidney exchange on the basis of HLA-matching is already cost-effective in the first year after grafting. PMID- 8442237 TI - Transplantation--the issues: a cross curriculum programme for secondary schools. PMID- 8442238 TI - Relationship between clinical outcome, inpatient length of stay, and cost of renal transplantation at four US transplant centers. PMID- 8442239 TI - Effects of three immunosuppressive drug protocols on cadaver renal transplantation costs after 4 years of therapy. PMID- 8442240 TI - Is retransplantation cost effective? PMID- 8442241 TI - Toward a European charter for transplantation ethics. PMID- 8442242 TI - Donor families' attitude toward organ donation. The North Italy Transplant Program. PMID- 8442243 TI - Influence of social support and study course on attitudes of 18-year-old students toward cadaveric organ donation and transplantation. PMID- 8442244 TI - Tabulation of cases from the International Pancreas Transplant Registry and analysis of United Network for Organ Sharing United States Pancreas Transplant Registry data according to multiple variables. PMID- 8442245 TI - Evidence that a "four-cell cluster" may prime cytotoxic T-cells during graft rejection. PMID- 8442246 TI - Immunopathology of liver allografts and xenografts in nonhuman primates. PMID- 8442247 TI - Not donor but recipient dendritic cells are involved in human renal rejection. PMID- 8442248 TI - Coronary arteriopathy postcardiac transplant in a heterotopic piglet model: the role of matrix-cytokine interaction. PMID- 8442249 TI - Serial analysis of cytokines, adhesion molecule expression, and humoral responses during development of chronic kidney allograft rejection in a new rat model. PMID- 8442251 TI - Evidence that liver grafting suppresses allograft rejection and controls graft-vs host reaction. PMID- 8442250 TI - T cells mediating early acute kidney allograft rejection in the rat are different from those responsible for chronic rejection. PMID- 8442252 TI - Endothelial adhesion molecules in human liver grafts: overview on the differential expression of leukocyte ligand molecules. PMID- 8442253 TI - Tyrosine kinase-dependent lymphocyte signaling during allograft rejection. PMID- 8442254 TI - Vascular rejection diagnosis correlates with the development of donor-specific antibodies and with macrophage infiltration of the graft. PMID- 8442255 TI - Efficacy of photopheresis in the rescue therapy of acute cellular rejection in human heart allografts: a preliminary clinical and immunopathologic report. PMID- 8442256 TI - Delayed graft function is associated with an increased incidence of occult rejection and results in poorer graft survival. PMID- 8442257 TI - Role of interleukin-2-producing CD4+ T cells in acute rejection of class I major histocompatibility complex disparate rat heart allografts. PMID- 8442258 TI - Humoral rejection associated with antidonor lymphocytotoxic antibodies following liver transplantation. PMID- 8442259 TI - Acute interstitial nephritis of plasma cells: a new cause for renal allograft loss. PMID- 8442260 TI - Host cell infiltration of the intraepithelial compartment in small bowel transplantation. PMID- 8442261 TI - Acute rejection episodes: best predictor of long-term primary cadaveric renal transplant survival. PMID- 8442262 TI - Acute early allograft failure and the C3/macrophage phenomenon. PMID- 8442263 TI - Does acute tubular necrosis affect renal transplant outcome? The impact of rejection episodes. PMID- 8442264 TI - Changes of chronic kidney allograft rejection are reversible after retransplantation. PMID- 8442265 TI - Relationship between early vs late acute rejection and onset of chronic rejection in kidney transplantation. PMID- 8442266 TI - Kidneys from female donors are at increased risk for chronic allograft rejection. PMID- 8442267 TI - Chronic rejection of rat renal allografts: a novel subpopulation of infiltrating leukocytes in long-term surviving allografts. PMID- 8442268 TI - Implications of lymphocyte sensitivity to glucocorticoids in renal transplant recipients. PMID- 8442269 TI - Computer-assisted densitometric analysis for quantification of cell surface antigen expression in monkey cardiac allografts: correspondence to histopathologic grade of rejection. PMID- 8442270 TI - Daily determinations of serum lymphotoxin allows for accurate early diagnosis of hepatic allograft rejection. PMID- 8442271 TI - Characterization of antiendothelial cell and antiheart antibodies following heart transplantation. PMID- 8442272 TI - Effect of immunosuppression on chronic rejection in the rat aortic allograft model. PMID- 8442273 TI - Predictors of chronic rejection in renal transplant recipients. PMID- 8442274 TI - Neutrophils and macrophages are prominent in the pathophysiology of chronic rejection of rat kidney allografts. PMID- 8442275 TI - Inducible IL-2 on CD8 lymphocytes as a postoperative predictor of rejection in renal allograft recipients. PMID- 8442276 TI - Eosinophiluria as an indicator of kidney-pancreas transplant rejection. PMID- 8442277 TI - Fifty islets maintain euglycemia and survive longer than 200 islets in allogeneic and xenogeneic diabetic hosts. PMID- 8442278 TI - Human islet purification with discontinuous density gradients following cold storage of the pancreas. PMID- 8442279 TI - Isokinetic gradients: a new approach to reduce islet graft immunogenicity. PMID- 8442280 TI - Pancreatic islet allograft and xenograft survival in CD8+ T-lymphocyte-deficient recipients. PMID- 8442281 TI - Syngeneic islets transplanted into the thymus of newborn mice prevent diabetes and reduce insulitis in the NOD mouse. PMID- 8442282 TI - Occurrence and prevention of graft-vs-host disease after pancreaticoduodenal transplantation in the BB rat. PMID- 8442283 TI - Isolation of functional MHC class I-deficient islet cells. PMID- 8442285 TI - Prolongation of murine islet allograft survival by pretreatment of islets with 2 chloroadenosine. PMID- 8442284 TI - Transplantation of porcine fetal islet-like cell clusters into eight diabetic patients. PMID- 8442286 TI - Induction of unresponsiveness to islet allograft by anti-LFA-1 monoclonal antibody treatment. PMID- 8442287 TI - Combined transplantation of islets and kidney: immunogenetic analysis in the rat. PMID- 8442288 TI - Transplantation of islet allografts using a diffusion-based biohybrid artificial pancreas: long-term studies in diabetic, pancreatectomized dogs. PMID- 8442289 TI - Islet and hepatocyte cotransplantation in rats. PMID- 8442290 TI - Allo- and autotransplantation of porcine islets beneath the renal capsule and into the portal vein. PMID- 8442291 TI - Analysis of cytokine transcripts in pancreatic islet cell allografts during rejection and tolerance induction. PMID- 8442292 TI - Reduction in primary nonfunction of pancreas islet transplants with antithymocyte globulin agents, deoxyspergualin, and splenectomy. AB - These results suggest that DSG and RATG are an especially favored combination in reducing PNF of discordant pig islet xenografts, probably related to the effect of DSG on the macrophage, humoral antibody, or blockade of NK cell activity. More effective immunosuppression such as demonstrated in this study could well be critical in permitting the application on discordant islet xenografts to human clinical diabetes. PMID- 8442293 TI - Intrapancreatic islet transplantation as a potential solution to chronic failure of intraportal islet grafts. PMID- 8442294 TI - Allotransplantation of fresh and cryopreserved islets in patients with type I diabetes: two-year experience. PMID- 8442295 TI - Reversal of type II diabetes by pancreas islet transplant in four separate animal models of type II diabetes. PMID- 8442297 TI - Enterocyte transplantation using cell-polymer devices to create intestinal epithelial-lined tubes. PMID- 8442296 TI - Antibody formation after myoblast transplantation in Duchenne-dystrophic patients, donor HLA compatible. PMID- 8442298 TI - Endothelin and the respiratory system. AB - Pharmacological research involving the endothelin peptides has emphasized their activities in vascular systems, from both physiological and pathophysiological perspectives. However, the endothelins are known also to be synthesized and released from respiratory epithelial cells and to have potent effects in nonvascular components of the respiratory tract. Douglas Hay, Peter Henry and Roy Goldie summarize present understanding of the pharmacology of the endothelins in the respiratory system and assess the potential pathophysiological role in asthma. PMID- 8442299 TI - Mini-laparotomy staging pelvic lymphadenectomy (minilap). Alternative to standard and laparoscopic pelvic lymphadenectomy. AB - In a mini-laparotomy staging pelvic lymphadenectomy (minilap) a 6-cm lower midline abdominal incision is used to perform a complete pelvic lymphadenectomy. If the pelvic lymph nodes were positive for prostate cancer, the incision was closed without pelvic drains. If the pelvic lymph nodes were clinically negative for disease, the incision was extended, and a radical retropubic prostatectomy was done under the same anesthetic. The minilap was performed on 16 patients. Three patients who had grossly positive pelvic lymph nodes confirmed by frozen section examination were denied a radical retropubic prostatectomy and had a two to three-day hospital stay. The other 13 patients had an uneventful radical retropubic prostatectomy. We conclude that the minilap is an attractive alternative for patients requiring staging pelvic lymphadenectomy. PMID- 8442300 TI - Treatment of T3a bladder cancer with iridium implantation. AB - A total of 7 patients with high grade, T3a (Stage B2) bladder cancer were treated with external radiation therapy and interstitial iridium implantation from May 1986 through March 1988. Follow-up has ranged from nineteen to sixty-one months with a median of forty months. One patient has required a cystectomy and is currently free of disease, and 1 patient has had recurrence of his cancer and metastatic carcinoma has developed; 5 are free of disease and have maintained their usual state of bladder function. Iridium implantation maintains bladder function and is effective therapy for selected individuals with localized, muscle invading bladder cancer. PMID- 8442301 TI - Can citrate therapy prevent nephrolithiasis? AB - This prospective study was done to help determine whether or not oral citrate therapy can elevate urinary citrate levels and reduce the incidence of recurrent calcium stones in patients with hypocitraturia (urinary citrate less than 320 mg/24 hr). The treatment group (Group I) consisted of 10 patients treated with oral citrate and hydration. The control group (Group II) was treated with hydration alone. In Group I, the new stone formation rate (stones per patient year) fell from 1.17 +/- 0.26 to 0.45 +/- 0.32 (p = 0.07) and the twenty-four hour urinary citrate excretion rose from 69 +/- 14 mg to 473 +/- 96 mg (p = 0.002). In Group II, the new stone formation rate fell from 0.9 +/- 0.25 to 0.27 +/- 0.13 (p = 0.03). The twenty-four-hour urinary citrate excretion increased, though not significantly, from 166 +/- 21 mg to 326 +/- 77 mg (p = 0.06). We conclude that oral citrate therapy can significantly increase urinary citrate levels in patients with recurrent stones associated with hypocitraturia but that oral citrate therapy and hydration were no better than hydration alone in reducing the incidence of recurrent stones. PMID- 8442302 TI - Use of vacuum tumescence device for impotence secondary to venous leakage. AB - The causes and treatment of venogenic impotence are still controversial. From September 1989 to April 1991, 317 men complaining of impotence were evaluated in our Erectile Dysfunction Clinic. Seventy patients were suspected of having venous leakage, and all men had dynamic cavernosography performed. Forty-seven of these 70 men (67%) had venous leakage, and a vacuum tumescence device was recommended as initial treatment for all of them. A questionnaire was later mailed to all 47 patients. A response to the questionnaire was obtained from 45 men (96%). Twenty nine patients had purchased a vacuum tumescence device (Osbon ErecAid). A satisfactory result was obtained in 20 patients (69%) with venous leakage. Since the use of the vacuum tumescence device is relatively safe and noninvasive, and the results are as good as or better than venous ligation, we recommend its use as the initial treatment of venogenic impotence until a consistently reliable treatment for this condition is found. PMID- 8442303 TI - Umbilicus preservation with total abdominal wall reconstruction in prune-belly syndrome. AB - A technique to preserve the umbilicus in abdominal wall reconstruction for prune belly syndrome is presented. Our technique has been utilized in 5 cases with success. PMID- 8442304 TI - Transurethral removal of knotted bladder drainage catheter in a male following bladder neck reconstruction. PMID- 8442305 TI - Abdominoscrotal hydrocele causing upper urinary tract displacement and obstruction. AB - We report on a case of abdominal hydrocele in which the abdominal component caused displacement and obstruction of the upper urinary tracts. We review the surgical management of this rare condition. PMID- 8442306 TI - Urethral prolapse in children. AB - We report our experience with 23 girls with urethral prolapse. Vaginal bleeding was the most common complaint, and predisposing factors (cough, trauma, and constipation) were found in 10 children. Although reported almost exclusively in black girls, 14 of the 23 patients were white. Three basic techniques were used for therapy: conservative management, ligation over a Foley catheter, and total excision of the prolapse. Ligation over a Foley catheter had a high incidence of complications (partial recurrence, infection, postoperative pain) and is no longer used. The best results were obtained by complete excision of the urethral prolapse. We propose that treatment should be based on the etiopathogenesis of the prolapse and the clinical condition of the child; patients with a single and acute episode of increased abdominal pressure, such as trauma, and those at high risk for general anesthesia are managed by conservative therapy. All others, and patients who fail medical treatment, undergo surgical excision. PMID- 8442307 TI - Simplified infusion method for 10% hemiacidrin irrigation of renal pelvis. AB - A variable pressure volumetric pump was used for 10% hemiacidrin irrigation of the renal pelvis in 7 renal units (6 patients) with struvite calculi after initial percutaneous debulking and extracorporeal shock-wave lithotripsy (ESWL). The pump provided a constant display of intrapelvic infusion pressure, and an alarm which signaled if a preset maximum infusion pressure was exceeded. Compared with standard open manometer monitoring of intrapelvic pressure, this closed system of irrigation eliminates the problems associated with time-consuming assembly and maintenance, irrigant spillage, and system contamination. At the completion of therapy, 5 renal units were completely stone-free while 2 had only minimal residual caliceal "dust." Complications were minor and few in number. We conclude that a variable pressure volumetric pump provides excellent clinical results and safely simplifies irrigation for percutaneous chemolysis of struvite calculi. PMID- 8442308 TI - Suprapubic tube tract dilation using the Otis urethrotome. PMID- 8442309 TI - Aztreonam. AB - Aztreonam is the first monobactam and is unique among beta-lactam antibiotics for its spectrum of activity that is exclusively active against gram-negative aerobic bacteria. Broad clinical experience with this agent supports its use in the treatment of adults with severe or complicated urologic infections. Aztreonam may be safely used in patients with penicillin allergy. With a spectrum of activity that is comparable to the aminoglycosides but without the potential for ototoxicity or nephrotoxicity, aztreonam represents a rational choice of therapy for treatment of systemic urinary tract infections due to susceptible organisms. PMID- 8442310 TI - Significance of CT-scan-detected seminal vesicle enlargement in prostate cancer. A pilot study. AB - The significance of CT-scan-detected seminal vesicle enlargement was investigated by correlating preoperative CT scans and pathologic findings for 25 patients undergoing radical prostatectomy. Seminal vesicle size was found to be a poor predictor of pathologic involvement when compared with tumor differentiation and obliteration of seminal vesicle angle. PMID- 8442311 TI - Sonography of epididymal leiomyoma. PMID- 8442312 TI - Thirty-nine-year-old woman with abdominal pain on right side. PMID- 8442313 TI - Use of artificial sphincter to bowel segment using rectus muscle interposition. AB - The use of artificial urinary sphincter around the urethra or bladder neck for the management of urinary incontinence secondary to intrinsic urethral sphincter deficiency is now well accepted. However, its use around the bowel to serve as a sphincter in urinary pouches is still anecdotal. Its use in experimental models has been met with failure because of ischemic bowel necrosis at the cuff site. To obviate these difficulties, a new technique was devised using a flap of rectus muscle that acted as a cushion between the cuff and the bowel wall. Results in five dogs showed that bowel wall ischemia is avoided with cuff pressure of 51-60 cm applied constantly for four weeks while providing pressure to leak around the closed cuff with a pressure of 62-75 cm water. Further study is needed to confirm the long-term effect of this technique on the bowel wall and the ability of the sphincter to maintain continence. PMID- 8442314 TI - Untreated hypernephroma of thirty-three years. AB - The literature cites long-term (> 10 years) survivals after surgical treatment for renal cell carcinoma compared with few untreated cases with similar survival. We report the longest survival between time of diagnosis and documented distant metastases from an untreated renal cell cancer. PMID- 8442315 TI - Candida epididymitis: newly recognized opportunistic epididymal infection. AB - Epididymitis is common, yet it is rarely associated with fungal pathogens. We report a case of Candida albicans epididymitis in a diabetic which was ultimately treated by orchiectomy. Opportunistic infections of the genitourinary tract in immunosuppressed patients are becoming more prevalent; examples include fungal infections in patients with acquired immune deficiency syndrome or after organ transplant. The fact that opportunistic organisms can invade the epididymis and produce infection suggests that in cases of persistent epididymitis, which have failed to respond to conventional therapy, more aggressive diagnostic procedures should be considered. Needle aspiration with cultures for fungus and viral organisms should be performed. This is especially true in patients with preexisting chronic illness or an immune compromised state. PMID- 8442316 TI - Acute lobar nephronia of renal transplant allograft. AB - Acute lobar nephronia (acute focal bacterial nephritis) has recently been recognized as an infectious process of the kidney. It is a radiologic diagnosis characterized as a nonliquifiable inflammatory renal mass associated with signs and symptoms of bacterial pyelonephritis. We present the successful management of a renal allograft recipient who had radiologic evidence of acute lobar nephronia within the graft six weeks after placement of an internalized ureteral stent. PMID- 8442317 TI - Unilateral acquired renal cystic disease and neoplasia in a patient with renal artery stenosis. AB - We report a case of a sixty-two-year-old woman with longstanding unilateral renal artery stenosis in whom acquired renal cystic disease (ARCD) and neoplasia developed. ARCD has been frequently reported in the hemodialysis and peritoneal dialysis patients, but rarely reported in the nonuremic patient. To our knowledge it has not been previously reported in a patient with unilateral renal artery stenosis. PMID- 8442318 TI - Carcinosarcoma of urothelial organs: sequential involvement of urinary bladder, ureter, and renal pelvis. AB - We report a case of true carcinosarcoma involving the urinary bladder, ureter, and renal pelvis in an eighty-year-old man. The patient underwent transurethral resection of the bladder tumor and left nephrectomy, followed by combination chemo- and radiotherapy. He died eighteen months after the nephrectomy. PMID- 8442319 TI - Primary renal carcinoid tumor. AB - We report a case of primary renal carcinoid tumor. Only 13 prior cases are documented in the literature. The tumor fulfilled both histologic and immunochemical criteria for carcinoid. In addition, we employed new diagnostic modalities (i.e., magnetic resonance imaging and chromogranin-A levels) not used in prior published reports. A review of the literature is presented. PMID- 8442320 TI - Cystoscopy and ascertaining ability of ureter to efflux at UVJ. PMID- 8442321 TI - Measuring irrigating fluid absorption during TURP. PMID- 8442322 TI - Histopathologic lesions in sea otters exposed to crude oil. AB - Following the Exxon Valdez oil spill in Prince William Sound, Alaska, sea otters (Enhydra lutris) that appeared to be contaminated with oil, that were in danger of becoming contaminated, or that were behaving abnormally were captured and taken to rehabilitation centers. Exposure to oil was assessed by visual examination when otters arrived at the centers. Degree of oil exposure was graded according to the following criteria: oil covering greater than 60% of the body- heavily contaminated; oil covering 30-60% of the body--moderately contaminated; oil covering less than 30% of the body or light sheen on fur--lightly contaminated. If there was no oil visible, otters were considered uncontaminated. Tissues from 51 oil-contaminated sea otters (14 males, 37 females) and from six uncontaminated sea otters (three males, three females) that died in rehabilitation centers were examined histologically. Among oil-contaminated sea otters, 19/46 had interstitial pulmonary emphysema, 13/40 had gastric erosion and hemorrhage, 11/47 had centrilobular hepatic necrosis, 14/47 had periportal to diffuse hepatic lipidosis, and 10/42 had renal tubular lipidosis. Of the uncontaminated sea otters, 1/6 had gastric erosion and hemorrhage and 1/6 had diffuse hepatic lipidosis. Histologic examinations were performed on tissues from five sea otters (three males, two females) found dead with external oil present 15 to 16 days after the spill. Periportal hepatic lipidosis and renal tubular lipidosis were found in 3/5, and interstitial pulmonary emphysema was found in 1/5. Tissues from six apparently normal sea otters (four males, two females) collected from an area not affected by an oil spill were examined histologically, and none of these lesions were found. We conclude that interstitial pulmonary emphysema, centrilobular hepatic necrosis, and hepatic and renal lipidosis of sea otters were associated with exposure to crude oil. Gastric erosion and hemorrhage may have been associated with stress of captivity and/or oil exposure. PMID- 8442324 TI - Prognostic factors in canine mammary tumors: a multivariate study of 202 consecutive cases. AB - The prognostic variables of 223 consecutively sampled spontaneous mammary tumors from female dogs were studied. These variables included flow cytometric DNA analysis and cell proliferation measured as cells in S-phase rate evaluated from DNA histograms. The dogs were surgically treated, in most cases with unilateral mastectomy (all mammary glands), and 202 of the 223 dogs were studied temporally following surgery. Univariate analysis with correction for age indicated that the variables of lymph node metastasis, elevated S-phase rate, presence of a sarcoma, DNA aneuploidy, and ulceration and infiltrative growth into underlying tissue had a statistically significant negative influence on the survival rates of dogs with a diagnosed malignant tumor. Similar results were obtained from tests on all dogs, but tumor size and its relative hazard increased with increasing size of the tumors, regardless of whether total or disease-specific mortality was considered. Using multivariate-analysis conducted Cox's proportional hazards model, elevated S-phase rate, increased age, and presence of a sarcoma remained statistically significant risk factors. The prognostic value of DNA ploidy and lymph node status varied depending on choice of end point. The study of tumor growth pattern and tumor size provided no prognostic information in the multivariate analysis. Flow cytometric cell analysis, including S-phase rate and DNA ploidy, is of value in predicting the prognosis of canine mammary tumors and can be used as a new prognostic tool to improve the preoperative diagnostics of canine mammary tumors. PMID- 8442323 TI - Two types of bacteria adherent to bovine respiratory tract ciliated epithelium. AB - Two hundred sixty tracheas were obtained from a Philadelphia abattoir under permit from the Department of Agriculture; the tracheas were excised from predominantly Holstein calves of both sexes that weighed approximately 250 kg. Tracheas were transported in normal saline to the laboratory at Thomas Jefferson University, Philadelphia, Pennsylvania. Evidence of bacteria adherent to the tracheal epithelium was found in specimens from 20/24 of these tracheas. The epithelium from each of five tracheas was placed in glutaraldehyde fixative for transmission electron microscopic examination. Epithelium from each of 12 other tracheas was placed in formaldehyde fixative for light microscopic examination. Microscopically, 13 of these 17 bovine tracheal epithelia were observed to contain bacteria located longitudinally parallel to and between cilia and microvilli of ciliated cells. Preparations of ciliary axonemes isolated from the epithelium of seven additional bovine tracheas also contained these bacteria in sections viewed by a transmission electron microscope. These bacteria had two different ultrastructural morphologies: filamentous with a trilaminar-structured cell wall and short with a thick, homogeneously stained cell wall beneath a regularly arrayed surface layer. The short bacillus had surface carbohydrates, including mannose, galactose, and N-acetylgalactosamine, identified by lectin binding. The filamentous bacillus was apparently externally deficient in these carbohydrates. Immunogold staining revealed that the filamentous bacillus was antigenically related to cilia-associated respiratory (CAR) bacillus, which has been identified in rabbit and rodent species. Significantly decreased numbers of cilia were obtained from tracheal epithelium heavily colonized by the filamentous bacilli, suggesting a pathologic change in ciliated cells. PMID- 8442325 TI - Thrombosis of the portal vein in eleven dogs. AB - Case records from the small animal necropsy service of the University of Pennsylvania (Philadelphia, PA) from January 1981 through August 1990 were searched for reports of animals with grossly visible portal vein thrombi. Eleven dogs identified from their case materials as having portal vein thrombosis were used for this study. The age of the dogs ranged from 2 to 13 years, and there were five spayed females and six males--four intact and two castrated. Seven breeds were represented (Lhasa Apso, German Wire haired Pointer, Shetland Sheepdog, Dalmatian, Irish Wolfhound, Old English Sheepdog, and Siberian Husky), and the remaining four cases were identified as mixed breeds. The weight of the dogs ranged from 7.7 to 50 kg, and most of them were considered overweight. Dogs with microthrombi and tumor emboli in the portal vein were excluded. No age, sex, or breed predisposition was found. Thrombi were also detected in the pulmonary arteries in five of the dogs and both the pulmonary arteries and aorta in one dog. The portal thrombi extended into the mesenteric veins in three dogs, resulting in infarction of the jejunum. One of these dogs and two other dogs had chronic occlusion of the portal vein, with the formation of secondary portosystemic shunts. Conditions also present in dogs with portal vein thrombi included pancreatic necrosis (four dogs), peritonitis (two dogs), distant neoplasia (three dogs), and therapy with steroids (ten dogs). PMID- 8442326 TI - Neuropathology of chronic wasting disease of mule deer (Odocoileus hemionus) and elk (Cervus elaphus nelsoni). AB - The pathology of the central nervous system of nine mule deer (Odocoileus hemionus) and six elk (Cervus elaphus nelsoni) with chronic wasting disease, a spongiform encephalopathy of mule deer and elk, was studied by light microscopy. Lesions were similar in both species and were characterized by spongiform transformation of gray matter, intracytoplasmic vacuolation of neurons, neuronal degeneration and loss, astrocytic hypertrophy and hyperplasia, occurrence of amyloid plaques, and absence of significant inflammatory response. Distribution and severity of lesions were evaluated at 57 locations; there were only minor differences between deer and elk. Consistent, severe lesions occurred in olfactory tubercle and cortex, hypothalamus, and the parasympathetic vagal nucleus of deer, and sections examined from these regions would be sufficient to establish a diagnosis of chronic wasting disease. Lesions were milder in these locations in elk but were sufficiently apparent to be of diagnostic value. Other differences included increased severity of lesions in some thalamic nuclei in elk in contrast to deer, the occurrence of amyloid plaques demonstrable by hematoxylin and eosin and histochemical stains in deer in contrast to elk, and the presence of mild white matter lesions in elk but not in deer. Lesions of chronic wasting disease were qualitatively comparable to those of scrapie, bovine spongiform encephalopathy, transmissible mink encephalopathy, and the human spongiform encephalopathies. Topographic distribution and lesion severity of chronic wasting disease were most similar to those of scrapie and bovine spongiform encephalopathy. Duration of clinical disease did not significantly influence lesion distribution or severity in either species. PMID- 8442327 TI - Spontaneous diabetes mellitus in young cattle: histologic, immunohistochemical, and electron microscopic studies of the islets of Langerhans. AB - Pathomorphologic studies were carried out on three cases of bovine diabetes mellitus with clinical signs of polydipsia, polyuria, severe emaciation, glycosuria, persistent hyperglycemia, and decreased glucose tolerance. At necropsy, two animals had atrophy of the pancreas, whereas other visceral organs, including the endocrine organs, showed no significant changes. Microscopically, there was atrophy and reduced numbers of pancreatic islets accompanied by interlobular and interacinar fibrosis and compensatory enlargement of some remaining islets. Lymphocytes were observed commonly around and within atrophic islets and occasionally around and within enlarged islets. Vacuolar degeneration with occasional accumulation of glycogen granules was observed in the beta-cells of these enlarged islets. Immunohistochemical studies of atrophic islets demonstrated complete loss of beta-cells or only a few small beta-cells. There also was a corresponding decrease in the number of cells that stained with anti glucagon (alpha-cells) or anti-somatostatin (delta-cells) antibodies. The vacuolated cells in the enlarged islets stained strongly with anti-insulin antibody (beta-cells). Ultrastructurally, the majority of cells in the atrophic islets had reduced cytoplasmic volume and few secretory granules, features consistent with alpha-cells. In contrast, enlarged islets that had prominent immunohistochemical staining for insulin (beta-cells) consisted of beta-cells with cytosolic edema, mitochondrial swelling, dilated smooth endoplasmic reticulum, and reduced numbers of or degranulated secretory granules. These pathomorphologic features found in cattle are similar to those found in juvenile onset insulin-dependent diabetes mellitus in human beings and suggest autoimmune involvement in diabetes. PMID- 8442328 TI - Epizootic gastritis associated with gastric spiral bacilli in cheetahs (Acinonyx jubatus). AB - An outbreak of vomiting in a group of captive cheetahs (Acinonyx jubatus) was investigated, and histologic examination revealed chronic gastritis characterized by infiltration of lymphocytes and numerous plasma cells and epithelial erosions. Lymphoid follicles, globule leukocytes, scattered neutrophils, and (in one animal) abscessed gastric glands were inconsistent findings. In addition, necropsy of three cheetahs revealed gastric mucosal hyperplasia. Two kinds of bacteria were identified in the stomachs of infected cheetahs. Numerous long, tightly coiled motile Gastrospirillum-like organisms were seen in gastric mucus and in Warthin-Starry-stained sections of mucosa. These bacteria could not be cultured but were transmitted to conventional mice in homogenates of gastric mucosa from infected cheetahs. Ultrastructural examination revealed helical filaments on some of these bacteria. In addition, a smaller Helicobacter sp. was isolated. This organism could be cultured in vitro under microaerophilic conditions. One or both of these bacterial species was probably responsible for the gastritis in these cheetahs. PMID- 8442329 TI - Pulmonary arterial changes in feline dirofilariasis. AB - Eleven cats with spontaneous dirofilariasis were necropsied; ten were domestic shorthairs and one was a Persian. The cats ranged in age from 1 to 10 years, and 6/11 cats were male. One to three heartworms were present in the right ventricle and pulmonary arteries of each of the 11 cats. Patchy areas of rugose thickening of the intima of the pulmonary trunk and marked villous endarteritis of lobar and medium-sized pulmonary arteries were observed. Affected larger vessels were partially occluded by large villous intimal proliferations that were lined by hyperplastic endothelial cells supported by connective tissue stroma. Moderate to marked infiltration of eosinophils and mononuclear inflammatory cells was consistently observed in the intima of affected larger pulmonary arteries. Thrombosis of pulmonary arteries was seen in five cats. Medial hypertrophy, mild intimal proliferative changes, and focal infiltrations of leukocytes were seen in small pulmonary arteries. Lesions indicative of right-sided heart failure consisting of right ventricular dilation and chronic passive congestion of the liver were observed in four cats. PMID- 8442330 TI - Crescentic cataracts in Alderley Park rats. AB - The ophthalmoscopic appearances and the clinical evolution of a previously poorly documented form of crescentic cataract was studied in over 2,000 untreated Alderley Park rats between 4 and 110 weeks of age. In addition, 401 ex-breeder females, 54 gonadectomized males, and 56 gonadectomized females of the same strain were studied. The light microscopic features of the lenticular changes were also examined in detail. The cataracts, crescentic in shape and originating dorsally at the lens equator, were mostly unilateral. They appeared from about 30 weeks of age and affected 4% of intact males and 14% of intact females by about 2 years of age. Fewer cataracts were found in ex-breeder females, and none were found in male or female gonadectomized rats up to 2 years of age. The cataracts developed rapidly and became fully formed in 3 months. Subsequently, most cataracts scarcely progressed. Only a few extended to involve the entire lens. Some appeared to regress completely. Histologically, affected lens fibers showed swelling, globular disintegration, and liquefaction, most marked in the cortex medial to the lens bow area and extending along the direction of the lens fibers in an anterior and posterior direction but only occasionally reaching the lens capsule. The cause of these age-related lenticular changes in the Alderley Park rat is uncertain, but these changes are important during the conduct of long-term studies with this strain because their incidence can be modulated by agents that alter sex hormone status. PMID- 8442331 TI - Superficial necrolytic dermatitis (necrolytic migratory erythema) in dogs. AB - Twenty-two dogs with superficial necrolytic dermatitis were evaluated prospectively, twenty-one of which had characteristic crusting lesions of the paw pads. Histologically, epidermal lesions included parakeratosis and laminar intracellular edema. The plasma amino acid concentrations of eight dogs were markedly depressed. Nine dogs had terminal diabetes mellitus. These clinical and morphologic findings were strikingly similar to those of necrolytic migratory erythema in human beings, the most common cause of which is hyperglucagonemia due to islet cell tumor of the pancreas. No pancreatic tumors were found in these dogs; plasma glucagon concentrations in the five dogs tested were normal. The serum alkaline phosphatase concentrations were elevated in all dogs. Severe vacuolar hepatopathy, suggesting metabolically or hormonally induced hepatic dysfunction, was found in 21 dogs at necropsy or by biopsy; one dog had ultrasonographic abnormalities of the liver. Histopathologically, severe vacuolar alteration resulted in parenchymal collapse and nodular regeneration, which grossly mimicked cirrhosis. Although the definitive metabolic stimulus was not discovered for the cutaneous and hepatic lesions, the similarity of the cutaneous and biochemical features of canine superficial necrolytic dermatitis to human necrolytic migratory erythema warrants further investigation into possible underlying pancreatic hormonal dysfunction. PMID- 8442332 TI - A role for computers in meat hygiene. PMID- 8442333 TI - Temporary bilateral laryngeal paralysis in a horse associated with general anaesthesia and post anaesthetic myositis. AB - An eight-year-old Highland pony which had previously shown normal laryngeal function, underwent general anaesthesia for surgical treatment of a mandibular sinus. During its recovery from the anaesthesia, the pony suffered great respiratory distress and stridor, due to total bilateral laryngeal paralysis and pulmonary oedema. The animal was immediately given a temporary tracheostomy. Some hours later, postoperative myositis developed; it resolved within two days and the pony's laryngeal function returned to normal during the following year. PMID- 8442334 TI - Efficacy of abamectin against nematodes in cattle. AB - Eight controlled trials were conducted, using 96 cattle of European breeds, to evaluate the efficacy of abamectin against natural and artificially acquired infections of adult and fourth-stage larvae of all the economically important gastrointestinal nematodes and lungworms in Germany and the United Kingdom. Half the animals were treated on one occasion with abamectin at a dose of 200 micrograms/kg bodyweight given subcutaneously while the other half remained untreated. Worms were counted 14 or 21 days after treatment or 28 days after the last infection. The treatment was highly effective (> 99 to 100 per cent) (P < 0.05) at removing immature (L4) stages and adult worms of the following species: Ostertagia ostertagi (inhibited larvae included), Trichostrongylus axei, Haemonchus contortus, Bunostomum phlebotomum, Cooperia species Oesophagostomum radiatum and Dictyocaulus viviparus. Naturally acquired adult C surnabada and Trichuris discolor infections were also significantly (P < 0.05) reduced. For Nematodirus helvetianus the efficacy varied from 89.8 to > 99 per cent (P > 0.1 to < 0.01). Abamectin gave full protection against the gastrointestinal nematodes O ostertagi, H contortus, Cooperia species and O radiatum for at least seven days and against the lungworm D viviparus for at least 14 days after treatment. PMID- 8442335 TI - Relationship between negative skin test with Johnin after vaccination and post mortem findings. AB - One hundred and seventy-six cattle, vaccinated against paratuberculosis in the first month of life with a whole-cell inactivated vaccine, containing Mycobacterium paratuberculosis suspended in a water/oil emulsion, were tested with intradermal Johnin between the ages of five and 14 months. Negative results in the skin test occurred more frequently in animals found positive in post mortem examinations (P = 0.008) using histological, microscopical and cultural techniques. PMID- 8442336 TI - Production of bovine calves following separation of X- and Y-chromosome bearing sperm and in vitro fertilisation. PMID- 8442337 TI - Swollen head syndrome is not associated with turkey rhinotracheitis virus. PMID- 8442338 TI - The veterinary surgeon's duty of care in handling and disposing of clinical waste. PMID- 8442339 TI - Policy on welfare. PMID- 8442340 TI - Policy on welfare. PMID- 8442341 TI - Policy on welfare. PMID- 8442342 TI - Control of sheep scab. PMID- 8442343 TI - Dermatitis/nephropathy syndrome of pigs. PMID- 8442344 TI - Cannibalism in laying hens. PMID- 8442346 TI - Referral cases. PMID- 8442345 TI - Causes of trauma in broilers. PMID- 8442348 TI - The saga of rural health care. PMID- 8442347 TI - Retention of progestogen sponges in ewes. PMID- 8442349 TI - An epidemic of caterpillar sting dermatitis in a rural West Virginia community. AB - During a five-week interval which began May 1991, 19 patients presented to a community health center in a rural West Virginia community with a painful dermatitis. The dermatitis was caused by exposure to a single species of caterpillar, Hemileuca maia, larva of the buck moth. The caterpillars were apparently especially abundant during the period. Epidemics of caterpillar stings rarely have been reported. No previous epidemics of stings by the buck moth caterpillar have appeared in the literature. PMID- 8442350 TI - Hypercoagulable states. AB - A hypercoagulable state is an enhanced tendency to form venous or arterial thrombi. In 1845, Virchow postulated three factors responsible for thrombosis that remain relevant today: alterations of the blood (hypercoagulability); changes in vessel wall (vascular injury); and impairment of blood flow (stasis). An increased understanding of the molecular basis of thrombosis has been aided by the identification of individuals with specific inherited defects in the natural anticoagulation system. These primary hypercoagulable states include antithrombin III, protein C and protein S deficiencies, dysfibrinogenemias, plasminogen deficiency, and decreased plasminogen activator activity. Individuals with thrombosis at an early age, a family history of thromboembolic disease, unusual sites of thrombosis, or recurrent thrombosis without apparent cause should be evaluated for a primary hypercoagulable defect. The majority of patients do not have a recognizable specific defect. However, there are a variety of underlying conditions or diseases that are associated with an increased risk for thrombosis. The etiologies of secondary hypercoagulable states are often unclear and may be multifactorial. Treatment of these inciting conditions or diseases may decrease the thrombotic tendency. PMID- 8442351 TI - The "T" word. PMID- 8442352 TI - The medical community. PMID- 8442353 TI - [Sleep disorders in neurology: hyposomnia]. AB - Sleep disturbances are an important health problem; about 20-33% of the population suffer from hyposomnias (lack of sleep). Hyposomnias often accompany neurological disorders (head traumas, chronic cephalea, pain, cerebrovascular and neuromuscular disorders, M. Parkinson, and dementia). Slow wave sleep decreases, arousals increase, and sleep is fragmented; these types of hyposomnias are treated by treatment of the basic neurological disease. Some sleep disturbances (e.g. sleep apneas) are a risk factor for cerebrovascular disorders. PMID- 8442354 TI - [Tension headache--new evaluation of symptomatology based on International Headache Society diagnostic criteria]. AB - This study presents the history and clinical findings in 80 patients suffering from tension-type headache diagnosed according to the criteria (group 2) proposed in 1988 by the Headache Classification Committee of the International Headache Society (IHS). The aim of this investigation was to evaluate the extent to which the symptomatology in our cases still corresponds with the clinical picture of tension headache described in the older literature. A positive family history of headache was obtained in 59% of the patients; mothers of headache patients were affected five times more often than fathers; a history of migraine was reported as frequently as tension-type headache in the families of the investigated patients. The first manifestation of headaches arose almost exclusively in the first four decades of life, whereby two peaks (15-20 and 35-40 years) were observed in patients with the episodic form. Headache in younger patients showed no distinct diurnal pattern; headache in older patients, however, predominantly occurred immediately after awakening from sleep or in the morning. Changes of weather and psychosocial stress were the most frequent precipitating factors; additionally, the premenstrual period, occupational stress, and sleep deprivation were precipitating factors in female patients. Bilateral pain was most often located in the occipital/nuchal, in the frontal, and the periorbital regions. Headache was usually described as pressing/tightening in quality. Difficulties in concentration and the need of rest were the most important associated symptoms. Photophobia, phonophobia and autonomic symptoms were less frequent and are probably partially drug-related and may also be due to the fact that the selected group of patients suffered from severe forms of headache. 33 of our 80 patients belonged to the subgroup "with disorders of pericranial muscles" (IHS criteria: groups 2.1.1., 2.2.1). A remarkable low percentage of patients, especially of the male sufferers, reported regular smoking and/or drinking habits. Oral contraceptives influenced neither frequency nor intensity of headache attacks. Signs of depressive disorders were present in 28% of the female patients. The differences in symptomatology of tension-type headache between patients with episodic and chronic forms, between female and male patients, and also between younger and elderly patients are documented and have to be taken into account in the diagnostik evaluation of this condition. PMID- 8442355 TI - [Disk hernia, operate or not?]. AB - There is often a high degree of uncertainty concerning the treatment of disc hernias. In cases with uncertain indication for operation only few hard data are available to base therapeutic decisions on. According to the few available controlled studies, which are discussed in detail, surgery yields better results only in the first year after surgery. There is no difference in the longer-term prognosis between surgery and physiotherapy. The need for further controlled trials using modern imaging techniques is obvious. PMID- 8442356 TI - [Incidence of Haemophilus influenza meningitis in Austria]. AB - The incidence of Haemophilus influenza meningitis was analysed for the first time in Austria. In 1990 a total of 55 cases occurred, representing an incidence of 0.71/10(5). Most of the patients were children aged less than 5 years (n = 42, 76.4%). The incidence in the age group 0-4 years was 9.48/10(5), in each of the other 5-year age groups the incidence was lower than 1/10(5). PMID- 8442357 TI - [Mefloquine and sulfadoxine/pyrimethamine overdose in malaria tropica]. AB - A 39 year-old man with malaria due to Plasmodium falciparum received 3500 mg mefloquine over 3 days, in addition to 3250 mg chloroquine and 175/3500 mg sulfadoxine/pyrimethamine. He developed severe neuropsychiatric symptoms and had to be hospitalized. Treatment with diazepam, haloperidol and thioridazine achieved relief of the severe symptoms after 4 days. The patient was still suffering from discrete neuropsychiatric symptoms 8 months after treatment. PMID- 8442358 TI - [The relevance of functional findings in early stages of senile macular degeneration]. PMID- 8442359 TI - [15th symposium for attorneys and physicians. 10-11 January 1992. Subject: euthanasia, terminal care]. PMID- 8442360 TI - [Definition of concepts: assisted death, assisted suicide, euthanasia, passive euthanasia, homicide--from the legal viewpoint]. PMID- 8442361 TI - [Definition of concepts: assisted death, assisted suicide, euthanasia, passive euthanasia, homicide--from the medical viewpoint]. PMID- 8442362 TI - [Personal death and the death of others. Reflections on the history of euthanasia]. PMID- 8442363 TI - [Euthanasia by request--from the legal viewpoint]. PMID- 8442364 TI - [Euthanasia by request--from the medical viewpoint]. PMID- 8442365 TI - [Experiences in the Netherlands with "euthanasia by request"]. PMID- 8442366 TI - [Euthanasia without request--euthanasia in impaired judgment]. PMID- 8442367 TI - [Ethical aspects of euthanasia--from the Catholic theology viewpoint]. PMID- 8442368 TI - [Ethical aspects of euthanasia--from the Protestant theology viewpoint]. PMID- 8442369 TI - [Ethical aspects of euthanasia--from the medical viewpoint]. PMID- 8442370 TI - [The psychology of dying and death]. PMID- 8442371 TI - [Alternative model. Euthanasia--a psychiatric viewpoint]. PMID- 8442372 TI - [Terminal care]. PMID- 8442373 TI - [Functional disease pictures without pathologic organ findings--a challenge for the internist]. AB - Many patients suffer from symptoms related to pathomorphologically healthy organs. Typical symptom patterns may be defined as functional disease entities. No demonstrable pathomorphologic alterations mean normal clinical findings, normal results of laboratory tests and function studies, absence of abnormal findings in imaging techniques, and normal results of cytologic or histologic investigations. Symptom patterns of functional diseases are usually impressive and clear, allowing a primary diagnosis, which of cause must be verified by excluding possible differential diagnoses. Early diagnosis has a heavy impact on later course and prognosis. From a certain point of chronicity, functional diseases become more or less refractory to therapy. Neglection of the correct diagnosis may therefore promote chronic disease. The main reason for a misleading diagnosis is the unreadiness of physicians and patients to accept and to face the functional, non-organic nature of symptoms. The main etiologic factor is psychosocial stress in most cases. Treatment is based on four different approaches, which may well be combined with each other: oral communication to clarify and to explain the nature of the disease, changing the all day way of life, supporting drug therapy, and specific psychosomatic treatment. PMID- 8442374 TI - [In former East Germany were diabetic patients not only "well managed", but also well treated?]. AB - The quality of diabetes care in the former GDR 1989/90 and in former West Germany 1990/91 was compared in a case control study. The study group consisted of 83% of the diabetic patients registered in the local diabetes care unit in Jena who were on insulin. The patients (86 women, 104 men; 131 Type-I and 59 Type-II, aged 16 60 years) were in the care of the local diabetes care unit. The control group consisted of randomly selected diabetic patients of the outpatient department of the university of Dusseldorf (matched pairs). Despite a different strategy of therapy the HbA1c (Jena/Dusseldorf) was the same: 154%/153% of the mean normal value in type-I and 178%/175% in type-II. The prevalence of retinopathy in type-I and type-II and proteinuria in type-I was not different, whereas the prevalence of proteinuria in type II- and of hypertension in both types of diabetes was higher in Jena. PMID- 8442375 TI - [Disorders of myocardial function in patients with normal coronary angiography]. AB - An attempt is made to estimate the value of intraventricular injection of contrast media in the procedure of angiocardiography for registration of a latent disease of the myocardium. For this purpose the parameter of the cardial function of 350 patients are analysed depending on the severity of the coronary heart disease. Under resting conditions the left ventricular end-diastolic pressure (LVEDP) of patients with coronary heart disease was 19.9 +/- 7.98 mmHg. The LVEDP of patients with the angina pectoris syndrome but normal epicardial coronary arteries was 15.6 +/- 5.45 mmHg. The LVEDP of the most of the patients rose after injecting contrast medium in the left ventricle independent of the resting level. Patients with coronary heart disease had a LVEDP of 23.7 +/- 9.48 mmHg after injecting the contrast media, while patients with normal coronary arteries had a LVEDP of 19.2 +/- 7.21 mmHg. The left ventricular systolic pressure and the parameters of contractility did not change significantly after injecting contrast media. The injection of contrast medium into the left ventricle--i.e. the ventriculography--is in a qualified sense a volume stress to the left ventricle. That means an increase of a normal LVEDP after an injection of contrast medium uncovers a preclinical disease of the left ventricular myocardium. PMID- 8442376 TI - [Meat from the nutritional medicine viewpoint]. AB - As in all forms of food, contaminants can also be present in meat. Because of the growing awareness of ecological and health issue, more tests with sophisticated equipment are now being implemented, thus reducing the risk of consuming contaminated meat. Meat has become the most heavily inspected form of food. In contrast to vegetable matter, animals can discharge many contaminants. Meat, with the exception of the liver and kidneys, is therefore less likely to be contaminated than vegetables. Facts show that meat is a highly nutritious food which, if consumed moderately, can contribute to our well-being. Meat contains the right combination of amino acids for protein synthesis in the human body, and especially it contains plenty of essential amino acids. Above all, meat contains many vitamins, trace elements, and iron. Large amounts of these substances are particularly necessary for growing children and people who are doing hard physical work. A reduction of meat consumption is only necessary in the case of a few illnesses. Some other illnesses actually require an increase in protein, and thus an increase in meat in the diet. PMID- 8442377 TI - [Stroke, epilepsy and abdominal pain as leading symptoms in a case of mitochondrial encephalomyopathy]. AB - A 17-year old girl presented with recurrent seizures, strokes, fatigue, vomiting, cerebellar ataxia, dementia and hypertrichosis. Further examinations showed jerking left-sided arm reflexes, partial internal deafness and myopathy. CT and MR of the skull revealed radiolucencies within the cerebral matter of the cortex and the medulla. Laboratory tests showed increased levels of lactate and pyruvate in serum and cerebro-spinal fluid. Microscopic examination of muscular tissue showed "ragged red fibers". Electron microscopy yielded crystal inclusions in mitochondria. The symptoms represented the complete picture of the so-called MELAS/MERRF-complex, which can be easily misdiagnosed as strokes and seizures of unknown cause. PMID- 8442379 TI - [Proving the effectiveness of drugs from the legal viewpoint]. PMID- 8442378 TI - [Excessive alcohol abuse]. AB - We studied 259 patients (m: 204, f: 55) admitted to our observation ward after drinking alcohol with blood levels above 3.9 g/l. Epidemiological data, clinical and laboratory data and therapeutic procedures were registered. Our analysis showed that such high blood levels of ethanol were only tolerated by a definite age-group of chronic alcoholics with mild organic injuries. Elevated mean cell volume and gamma-glutamyl transpeptidase and additionally low BUN may be useful markers for chronic alcohol consumption. PMID- 8442380 TI - [Developmental trends in the malpractice process]. PMID- 8442381 TI - [Possibilities and limits of medical graphology. Determination of current status and perspectives (II)]. PMID- 8442382 TI - Physical localization of the flocculation gene FLO1 on chromosome I of Saccharomyces cerevisiae. AB - The genetics of flocculation in the yeast Saccharomyces cerevisiae are poorly understood despite the importance of this property for strains used in industry. To be able to study the regulation of flocculation in yeast, one of the genes involved, FLO1, has been partially cloned. The identity of the gene was confirmed by the non-flocculent phenotype of cells in which the C-terminal part of the gene had been replaced by the URA3 gene. Southern blots and genetic crosses showed that the URA3 gene had integrated at the expected position on chromosome I. A region of approximately 2 kb in the middle of the FLO1 gene was consistently deleted during propagation in Escherichia coli and could not be isolated. Plasmids containing the incomplete gene, however, were still able to cause weak flocculation in a non-flocculent strain. The 3' end of the FLO1 gene was localized at approximately 24 kb from the right end of chromosome I, 20 kb centromere-proximal to PHO11. Most of the newly isolated chromosome I sequences also hybridized to chromosome VIII DNA, thus extending the homology between the right end of chromosome I and chromosome VIII to approximately 28 kb. PMID- 8442383 TI - Identification and genetic mapping of CHL genes controlling mitotic chromosome transmission in yeast. AB - Eight independent chl (chromosome loss) mutants were isolated using yeast haploid strain disomic for chromosome III. In these mutants, chromosome III is lost during mitosis 50-fold more frequently than in the wild-type strains. chl mutants are also incapable of stable maintenance of circular and linear artificial chromosomes. Seven of the eight mutations are recessive, and one is semidominant. Complementation tests placed these mutants into six complementation groups (chl11 through chl16). Based on tetrad analysis, chl12, chl14 and chl15 correspond to mutations in single nuclear genes. Tetrad analysis of the other mutants was not possible due to poor spore viability. Complementation analysis was also carried out between collection of chl mutants and ctf mutants (chromosome transmission fidelity) (Spencer et al., 1990). The chl3, chl4, chl8, chl12 and chl15 mutants were unable to complement ctf3, ctf17, ctf12, ctf18 and ctf4, respectively. Three CHL genes were mapped by tetrad analysis. The CHL3 gene is placed on the right arm of chromosome XII, between the ILV5 (33.3 cM) and URA4 (21.8 cM) loci. The CHL10 gene is located on the left arm of chromosome VI, 12.5 cM from the centromere. The CHL15 gene is tightly linked to the KAR3 marker of the right arm of chromosome XVI (8.8 cM). The mapping data indicate that these three genes differ from other genes known to affect chromosome stability in mitosis. Therefore, the total number of the CHL genes identified (including those described by us earlier) is 13 (CHL1-CHL10, CHL12, CHL14 and CHL15). PMID- 8442384 TI - The SCH9 protein kinase mRNA contains a long 5' leader with a small open reading frame. AB - The SCH9 yeast gene, that was previously identified as a suppressor of cdc25 and ras1- ras2-ts temperature-sensitive mutants, encodes a putative protein kinase that positively regulates the progression of yeast cells through the G1 phase of the cell cycle. We have determined the structure of the SCH9 transcription unit, using primer extension and S1 mapping techniques. The corresponding mRNA included an unusually long 5' region of more than 600 nucleotides preceding the major open reading frame (ORF). While the latter corresponded to a protein of 824 amino acids, an upstream open reading frame (uORF) within the 5' leader could potentially encode a 54 amino acid peptide. To investigate the role of the AUGs within the uORF, we engineered chimaeric plasmid vectors in which SCH9 sequences including the promoter, the mRNA leader and the first 514 nucleotides of the major ORF were fused in-frame with beta-galactosidase-coding sequences. Upon introduction into yeast cells, the fusion protein was efficiently expressed. However, mutational disruption of the uORF using oligonucleotide-directed mutagenesis did not affect the level of expression of the fusion protein. This indicates that regulatory mechanisms in Saccharomyces cerevisiae prevent upstream AUGs within the SCH9 mRNA leader sequence from influencing translation from downstream initiation codons. PMID- 8442385 TI - Stress resistance of yeast cells is largely independent of cell cycle phase. AB - Rapidly growing cells of Saccharomyces cerevisiae are sensitive to heat shock, while non-growing stationary phase cells are highly resistant. We find that slowly growing cells have an intermediate degree of heat shock resistance that can be nearly as great as that of stationary phase cells. This resistance is correlated both with slow growth and with carbon catabolite derepression. Slowly growing cells also showed resistance to Zymolyase digestion of their cell walls. The stress resistance is a property of all the cells in the culture, and cell cycle position makes little difference to the degree of stress resistance. At least some of the properties normally associated with stationary phase cells do not require residence in stationary phase or any other particular compartment of the cell cycle. Stress resistance may be due to a diverse set of physiological adaptations available to cells regardless of their position in the cell cycle. That is, although stress resistance and stationary phase are often correlated, neither is the cause of the other. PMID- 8442387 TI - Yeasts have a four-fold variation in ribosomal DNA copy number. AB - By employing pulsed-field gel electrophoresis we have determined the size of the rDNA cluster in wild-type yeast strains representing genera of Candida, Kluyveromyces, Pachysolen, Schizosaccharomyces and Torulaspora. Although the genome size of the examined species is similar (12.3-13.9 Mb), at least a four fold variation has been observed between the lowest amount of rDNA repeats in P. tannophilus (28) and the highest in C. glabrata and S. poombe (> 115). In two species the rDNA cluster is represented by two loci, residing either in one (S. pombe) or two chromosomes (C. glabrata). PMID- 8442386 TI - A yeast antiviral protein, SKI8, shares a repeated amino acid sequence pattern with beta-subunits of G proteins and several other proteins. AB - SKI8 is a yeast antiviral gene, essential for controlling the propagation of M double-stranded RNA (dsRNA) and thus for preventing virus-induced cytopathology. Our DNA sequence of SKI8 shows that it encodes a 397 amino acid protein containing two copies of a 31 amino acid repeat pattern first identified in mammalian beta-transducin and Cdc4p of yeast. There are also four copies of this repeat in yeast Mak11p, necessary for M dsRNA propagation, and three copies in the putative product of the Dictyostelium AAC3 gene. Analysis of 36 cases of the repeat unit shows they have a consensus predicted structure: N-helix-sheet-turn sheet-turn-sheet-helix-C. PMID- 8442388 TI - Human catalase is imported and assembled in peroxisomes of Saccharomyces cerevisiae. AB - To study the conservation of peroxisomal targeting signals, we have determined the intracellular localization of human peroxisomal catalase when expressed in yeast. Using immunofluorescence, differential centrifugation and immunoelectron microscopy, we show that the protein is targeted to the peroxisomes of the heterologous cell and assembled in its active tetrameric form. These data show the conservation of the catalase targeting signal and import specificity between human and yeast peroxisomes. PMID- 8442389 TI - Functional expression of bacterial beta-glucuronidase and its use as a reporter system in the yeast Yarrowia lipolytica. AB - The use of beta-glucuronidase (beta-GUS) as a reporter and sensitive detection system for Yarrowia lipolytica was studied. The Escherichia coli gusA gene was expressed under control of the homologous LEU2 promoter in a transcriptional fusion. An NcoI restriction site was introduced at the translational start-ATG, conserving the most favorable context for initiation of translation. The chimeric LEU2'-gusA gene was integrated into the LEU2 locus by homologous recombination. The beta-GUS assay was very sensitive and highly reproducible, using the cytosolic fraction or a total cell extract as the source of enzyme. In a leucine free medium, beta-GUS activity was at a high, constant level, independent of growth phase. In transformants grown on complete medium, beta-GUS activity was reduced about three-fold, but doubled during logarithmic growth. No intrinsic beta-GUS activity was detectable in untransformed Y. lipolytica and no effect of beta-GUS expression on growth was observed. beta-GUS-producing Y. lipolytica cells could be directly detected on media plates containing X-gluc (5-bromo-4 chloro-3-indolyl-beta-D-glucuronide). PMID- 8442390 TI - Yeast flocculation: flocculation onset and receptor availability. AB - Flocculent strains of brewing yeast grow and ferment as single cells and flocculate in the stationary phase of growth. The switch from single-celled yeast growth to multi-celled aggregation, flocculation onset, is of critical importance to the brewing industry. Yeast flocculation involves adhesion of surface-lectins on flocculent cells to carbohydrate receptors on neighbouring cell-walls. The presence of carbohydrate receptors, outer-chain mannan side-branches, was monitored throughout growth of flocculent and non-flocculent strains of Saccharomyces cerevisiae, with particular attention to the growth phases where flocculation is normally developed. Receptors were probed by coflocculation with flocculent strains and by aggregation with concanavalin A, a lectin shown to use the same receptors as flocculation. While considerable variation was found in coflocculation and concanavalin A aggregation between strains, little or no change in receptor availability was found throughout the growth of all yeast strains. Yeast cells could easily be coflocculated at any growth stage. It was concluded that receptor availability is not involved in the process of flocculation onset. PMID- 8442391 TI - Long-lasting neuropsychological changes after a single high altitude climb. AB - Acute neuropsychological changes due to high altitude climbing without supplementary oxygen are well known. However, many climbers report vague symptoms of brain dysfunction after return to sea level suggesting that long-lasting neuropsychological impairment may ensue even after a single ascent. In this study we evaluated a series of neuropsychological functions in a group of 11 climbers who ascended over 5000 m. Besides memory, also reaction time and concentration were less efficient when the climbers were evaluated 75 days after their return to sea level, confirming that even a single high altitude climb may be harmful for central nervous system functions. PMID- 8442392 TI - Prevalence of dementia in the city of Helsinki. AB - The Helsinki Aging Study is based on a random sample of 795 subjects aged 75 years (N = 274), 80-years (N = 266) and 85-years (N = 255). A clinical examination including Clinical Dementia Rating (CDR)-scale was carried out in 82% of the cases. 93 demented subjects were found, 17 of whom had mild dementia. The prevalence of moderate and severe dementia was 2.9%, 10.3% and 23.3% in the age groups of 75-year-olds, 80-year-olds and 85-year-olds, respectively. If we take into account also the mild cases, we get the prevalence of dementia 4.6%, 13.1% and 26.7% in the above mentioned age groups, respectively. The proportion of mild dementias was lower than expected, which probably reflects both the difficulties to recognize mild dementia in an elderly population and the relatively small compensatory capacity of elderly people. PMID- 8442393 TI - European Stroke Prevention Study (ESPS): antithrombotic therapy is also effective in the elderly. AB - The ESPS was a multicenter study comparing the effect of the combination of dipyridamole 75 mg and acetylsalicylic acid 330 mg t.i.d. to placebo in 2500 patients (intention-to-treat analysis) and 1861 patients (explanatory analysis) in the secondary prevention of stroke or death after one or more attacks of TIA, RIND or stroke of atherothrombotic origin. End-point reduction was evaluated in two age groups, those not older than 65 years (1358 patients) and those who were older than 65 years (1142 patients). End-point reduction was significantly greater in patients with active therapy than in the placebo group in both age groups. Subgroup analyses with stroke as an end-point indicated that younger patients with TIA (< or = 65 years) had lower risk of stroke than those > 65 years or patients with stroke. The overall risk reduction was best in TIA patients > 65 years of age. The risk reduction with study medication was 40-50% in both sexes and in both age groups. Thus, age of the patient does not influence the efficacy of antithrombotic therapy. However, since these results are obtained from a secondary analysis of a subgroup of patients, the results may need confirmation by further studies. PMID- 8442394 TI - Transient global amnesia: a quantified electroencephalographic study. AB - In 13 patients who experienced transient global amnesia (TGA), quantified electroencephalographic (qEEG) records were carried out within 1 week of the episodes, and compared with those in 13 cases with cerebral transient ischemic attacks (TIA), and 13 normal controls, matched for age and sex. A statistical comparison of the absolute power showed few differences between TGA and TIA patients, and many statistical differences between TGA patients and controls. The qEEG pattern reveals an involvement of the temporo-parietal structures in TGA patients. These findings suggest the presence of subclinical sequelae, after the TGA attack. PMID- 8442395 TI - Discrimination between neuropathy and myopathy by use of magnetic resonance imaging. AB - Since discrimination between myopathy and neuropathy may be difficult it seemed reasonable to investigate the possibility of assessment of these disorders by means of magnetic resonance imaging. Children with Duchenne muscular dystrophy and children with the juvenile type of spinal muscular atrophy were selected for the study and compared to healthy volunteers. Measurements were performed on a small Bruker imaging system operating at 2.35 T, and T1 weighed images on the lower extremities were recorded. Images obtained on the diseased extremities could be clearly distinguished from the images from healthy children. Furthermore, preferential involvement of fast muscles in patients with muscular dystrophy, and differences in distribution of fatty degeneration of muscles enable reliable discrimination between muscular dystrophy and spinal muscular atrophy. PMID- 8442396 TI - Motor impairment in Wilson's disease, I: Slowness of voluntary limb movements. AB - Twenty-three patients with Wilson's disease (WD) treated with D-penicillamine underwent clinical examination, as well as laboratory and motor testing. The clinical findings were scored. Laboratory tests included determination of the caeruloplasmin level, the free serum copper level, 24 h urinary copper excretion, liver enzymes and in 10 patients liver copper content of a liver biopsy. Laboratory tests and clinical scores were correlated. To quantify impairment of voluntary movements in WD fastest possible isometric index finger extensions and fastest alternating finger movements were analysed. Eleven patients presented with abnormally slow and 15 with abnormally irregular voluntary movements. Slowness of alternating movements correlated with the clinical score. The clinical score also correlated with the duration of symptoms prior to onset of therapy. Motor testing turned out to be sensitive enough to monitor improvement of neurological symptoms after onset of therapy. Comparison with motor testing in other basal ganglia diseases and cerebellar patients showed differences to patients with Parkinson's and Huntington's disease and similarities to patients suffering from AIDS-related dementia. In a small number of WD-patients similar results as in patients with a degenerative cerebellar disease were found. PMID- 8442397 TI - Motor impairment in Wilson's disease, II: Slowness of speech. AB - The maximal syllable production rate (MSPR) and the ability to reproduce a given target frequency in the 1 to 8 Hz range by repeating the short syllable "ta" was tested in 20 patients with Wilson's disease (WD) and 20 normal subjects. MSPR was significantly reduced in the WD-patients. In the 1 to 5 Hz range normal subjects as well as WD-patients tended to produce slightly higher frequencies than the target frequencies. This hastening was maximal in normals between 4 to 5 Hz whereas in the WD-patients hastening mainly occurred between 3 to 4 Hz. The test results showed a considerable variation across the patients. This variation can be interpreted on the basis of the theory of coupled oscillators. Comparison of speech and finger movements revealed a highly significant correlation between MSPR and the highest possible frequency of voluntary alternating index finger movements. As an application of the presented test treatment effects on speech movements were demonstrated. PMID- 8442398 TI - Effect of advanced brain atrophy and vitamin deficiency on cognitive functions in non-demented subjects. AB - The relationship between the cognitive functions, structural changes of the brain and vitamin levels was evaluated in 36 non-demented subjects with advanced brain atrophy, and 57 age- and sex-matched healthy controls. In the control subjects ageing was associated with mild decline of cognitive skills, but the cognitive changes were not linked to the structural changes of the brain. In contrast, advanced brain atrophy and vitamin deficiency was related to the decline of complex cognitive functions in the atrophy group. Our results indicate that there are limits of normal age-related changes of the brain structure, and advanced brain atrophy on CT scans increase the probability of mild deficits of the cognitive skills. PMID- 8442399 TI - Serum and CSF levels of soluble interleukin-2 receptors in MS and other neurological diseases: a reappraisal. AB - Soluble interleukin-2 receptors (sIL-2-R) were determined longitudinally in sera from 59 patients with multiple sclerosis (MS), from 20 patients with Guillain Barre syndrome (GBS) and from patients with other non-inflammatory disorders of the nervous system, as well as in 147 CSF samples collected for diagnostic purposes. Significantly increased serum levels of sIL2-R were observed early in the course of GBS and in progressive (relapsing or chronic) MS, but not in patients with clinically stable MS or with an acute relapse followed by complete remission. CSF levels were high in infections of the central nervous system and in meningeal carcinomatosis, as a result of an intrathecal production, but were normal in GBS and in most (94%) MS patients. PMID- 8442400 TI - A follow-up study of neuropsychological function in asymptomatic HIV-infected patients. AB - A group of asymptomatic HIV-infected patients (CDC II and III) was followed-up over a two year period with semi-annual neuropsychological testing. Of the total sample of 36 subjects, all were retested at test two (T2), 19 at test three (T3) and 13 at test four (T4). A subgroup of subjects was further tested on a simple and a complex task of reaction time. The CD4+ and CD8+ lymphocyte counts were measured in peripheral blood. According to our criteria, no patient could be defined as neuropsychologically impaired. A significant improvement in performance was found from T1 to T2 and from T2 to T3, with a leveling off between T3 and T4. No associations were observed between reaction time and changes in neuropsychological test results and immunological parameters. Our results indicate that neuropsychological impairment does not develop gradually in the asymptomatic stages of HIV-infection. Furthermore, measurements of reaction time do not seem to have any prognostic significance neither for neurocognitive function nor for immunological status as measured by us. PMID- 8442401 TI - Cognitive performance in HIV-1 infection: relationship to severity of disease and brain atrophy. AB - We examined cognitive performance in 72 HIV-1 infected patients and 34 controls. None of the patients had opportunistic infections or unusual neoplasms of the central nervous system (CNS). Factors other than HIV-1 known to cause cognitive decline were excluded from both groups. Cognitive functioning analysed with special emphasis on the severity of HIV infection was related to neuroradiological and immunological findings. In patients with AIDS-related complex (CDC IVa) or AIDS (CDC IVc,d), a deterioration of memory as well as cognitive speed and flexibility was detected. Furthermore, memory deficits were associated with central cerebral and infratentorial atrophy in those patients, while no association was found between cognitive deficits and immunological abnormalities. Patients at CDC stages II or III showed slight association between altered cognitive speed and flexibility and elevated leukocyte count, suggesting a subclinical CNS disease already at early stages of HIV infection. PMID- 8442402 TI - Myelography, CT, and MRI of the spinal canal in patients with myelopathy: a prospective study. AB - A prospective study including myelography, CT, and MRI was performed on 36 patients with clinical signs of myelopathy. Evoked potentials and spinal fluid examinations were also carried out. Based on our findings, the patients could be classified as suffering from cryptogenic myelopathy (n = 12), multiple sclerosis (n = 6), spinal stenosis (n = 6), or miscellaneous myelopathies (n = 12). The diameter of the spinal cord was normal in the 2 first groups of patients and of same magnitude evaluated by myelography and CT, while MRI constantly gave higher figures. In only four of the patients important new information was added by CT and MRI (syringomyelia, myelitis, lipomatosis) compared with myelography, although a more precise visualization was often provided. Further diagnostic progress in patients with myelopathy of undetermined etiology may be obtained by including supplementary MRI of the brain disclosing multiple sclerosis in several cases. PMID- 8442403 TI - Decreased axonal calibres without axonal loss in optic nerve following chronic alcohol feeding in adult rats: a morphometric study. AB - The effects of chronic ethanol exposure on number and calibres of optic nerve axons (and number of retinal ganglion cells) were investigated in a rat model. Male Sprague-Dawley rats were fed a liquid, ethanol-containing diet for 5, 10 and 17 weeks with littermates given isocaloric amounts of ethanol-free diet serving as controls. After fixation by perfusion, the optic nerves were imbedded in epoxy resin and sectioned for electron microscopy. Systematic random sampling was made from a cross-shaped area over the nerve. Axons within a counting frame were counted and morphometrically categorized with regard to mean diameter and the total number of axons estimated from number per area and the cross-sectional area of the nerve, which was measured using a digitizer table. According to non parametric statistical analysis, ethanol exposure resulted in a significant reduction in mean cross-sectional area of the optic nerve and in mean axonal calibre but not in total axonal number in the ethanol-treated rats but there was no significant effect of duration of the exposure. The mean cross-sectional area of the nerve was reduced by 9%, 10% and 18% after 5, 10 and 17 weeks of exposure, respectively. The reduction in cross-sectional area appeared to be related to a proportional reduction in axonal and myelin area fractions. The findings indicate that chronic ethanol exposure results in decreased axonal calibres without axonal loss. This also implies that there is no reduction in the number of retinal ganglion cells. PMID- 8442404 TI - Immunocytochemical and ultrastructural evidence of dendritic degeneration in motor neurons of aluminum-intoxicated rabbits. AB - Using immunocytochemical and ultrastructural methods, we observed extensive and characteristic dendritic changes in motor neurons of rabbits inoculated intracisternally with aluminum phosphate. Anti-microtubule-associated protein 2 immunostaining revealed markedly reduced immunoreactivity in motor neuron dendrites and a reduced number of dendritic trees in aluminum phosphate intoxicated rabbits. These dendritic changes were confirmed at the ultrastructural level; neurofilamentous accumulations, membranous inclusions and disrupted microtubules were common features of motor neuron axons. These observations suggest that dendrites are characteristically involved in aluminum intoxication in addition to the widely reported accumulation of phosphorylated neurofilament in perikarya and axons. PMID- 8442405 TI - Experimental allergic myositis in SJL/J mice immunized with rabbit myosin B fraction: immunohistochemical analysis and transfer. AB - Experimental allergic myositis (EAM) was produced in SJL/J mice by inoculation with the myosin B fraction of the rabbit skeletal muscle, and the pathological changes were quantified. The myosin B fraction contains actin, myosin, tropomyosin and many other proteins, and has been known to induce severe EAM in guinea pigs. In the present model, macrophages and CD4+ lymphocytes predominated among the infiltrating cells. On the surface of muscle fibers and in the regions of cell infiltration deposition of the immunoglobulin G (IgG) and complement factor 3 was observed. EAM was transferred to normal mice by injecting the serum IgG of EAM. Depleting the recipients of complement before the transfer resulted in less-severe pathological changes. Morphologically, the EAM IgG showed an affinity for the nuclei, myofilaments, sarcolemma and blood vessels of mouse skeletal muscle. Biochemically EAM IgG contained antibodies against myosin, actin, troponin, M protein and other muscle proteins. These results indicated that IgG and complement play important roles in this model. PMID- 8442407 TI - Measles virus infection of cells in perivascular infiltrates in the brain in subacute sclerosing panencephalitis: confirmation by non-radioactive in situ hybridization, immunocytochemistry and electron microscopy. AB - As part of continuing multidisciplinary studies on the neuropathogenesis of subacute sclerosing panencephalitis (SSPE), in situ hybridisation, immunocytochemistry and electron microscopy were used to detect measles virus nucleic acid, protein and nucleocapsids in brain perivascular infiltrates of three cases. Perivascular cuffing cells which contained measles virus nucleic acid and antigens were found in all cases. Infected cuffs occurred predominantly in areas of general parenchymal cell infection and in many of these a high proportion of the infiltrating cells were infected. Other cuffs in these areas were either uninfected or contained only a few infected cells. Occasional infected cells were also seen in cuffs in non-infected areas. In contrast, no specific immunocytochemical reactions or in situ hybridisation for measles virus was observed in brain tissue from a patient with herpes encephalitis. By electron microscopy viral nucleocapsid, consistent with measles virus, was found within the cytoplasm of plasma cells in the inflammatory cuffs in SSPE brain tissue. Possible explanations for our results are that infiltrates become infected on arrival in the CNS or alternatively, that the infected infiltrates reflect a generalised infection of the reticuloendothelial system. The frequent presence of uninfected cuffs favours the former explanation. PMID- 8442406 TI - Early perifocal cell changes and edema in traumatic injury of the spinal cord are reduced by indomethacin, an inhibitor of prostaglandin synthesis. Experimental study in the rat. AB - The possibility that prostaglandins participate in the formation of perifocal edema and cell changes following a localized trauma to the spinal cord was investigated in a rat model. A laminectomy was performed in urethane-anesthetized animals at the thoracic T10-11 segment. Using a scalpel blade a unilateral lesion, about 2 mm deep and 5 mm long was made 1 mm to the right of the midline. The deepest part of the injury occupied Rexed's lamina VII of the dorsal horn. Animals were pretreated with the prostaglandin synthesis inhibitor, indomethacin (10 mg/kg, i.p. 30 min prior to trauma). Five hours after the injury the water content was determined and cell changes in and around the primary lesion were examined by light and electron microscopy. Normal and injured rats without indomethacin pretreatment served as controls. Untreated injured rats showed a profound increase of water content in the traumatized T10-11, the rostral (T9) and caudal (T12) segments compared with normal rats. These segments also exhibited marked cell changes in ipsilateral and contralateral dorsal and ventral horns. The gray matter had a spongy appearance and some nerve cells were condensed and distorted. The white matter contained many distorted fibers. Immunostaining for myelin basic protein showed a marked reduction of reaction product in the injured animals compared with normal rats. Ultrastructurally widened extracellular spaces, cytoplasmic vacuolation, swollen and condensed neurons, swollen astrocytes and vesiculation of myelin were frequent findings. Pretreatment of rats with indomethacin significantly reduced the accumulation of water in the traumatized and in the rostral and caudal segments. The structural changes were less pronounced particularly in the cranial and caudal segments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8442408 TI - Monoclonal antibody to beta peptide, recognizing amyloid deposits, neuronal cells and lipofuscin pigments in systemic organs. AB - A monoclonal antibody (AmT-1) produced against synthetic amyloid beta peptide (1 28 residues) was revealed to be reactive with amyloid beta peptide blotted on nitrocellulose membrane, but not with that dissolved in sodium dodecyl sulfate and electrophoresed. AmT-1 immunostained senile plaques of typical, primitive and diffuse type, as well as amyloid deposits in cerebral vessels. It also reacted with neuronal and glial cells of normal and Alzheimer's disease (AD) brains. In addition, AmT-1 was also reactive strongly with lipofuscin pigments of adrenal reticular cells, and weakly with those of eccrine glands and liver cells. A rat neural cell line (PC12h) was reactive with AmT-1. By immunoelectron microscopy, a positive reaction was seen in ribosomes along the rough endoplasmic reticulum of nerve cells and PC12h cells. By immunoprecipitation, AmT1 reacted with a band at 36 kDa in the brain homogenates from Ad patients as well as from normal aged subjects. By immunoblotting analysis, AmT1 reacted with a band at 36 kDa in the cytosolic fraction of PC12 cells, and three bands (12-17 kDa) in the lipopigment fraction of the adrenal gland. These findings suggest that the cerebral amyloid deposits contain substance(s) having an epitope common to neuronal cells and lipofuscin pigments. The possible relationship between cerebral amyloid deposits and lipofuscin pigments in systemic organs is discussed. PMID- 8442409 TI - Neuronal damage in the cerebral cortex of AIDS brains: a morphometric study. AB - Using stereological methods, two cerebral cortical areas from AIDS brains were investigated. Neuronal density, profile area of neurons, and perikaryon volume fraction were measured and compared to age-matched control brains. In the fronto orbital cortex (area 11) of AIDS brains, a significant loss of neurons was seen. The perikaryon volume fraction was likewise decreased. The size of neurons did not differ between control and AIDS brains. In patients with clinical signs of progressive dementia and in brains with human immunodeficiency virus (HIV) specific neuropathology (HIV-leukoencephalopathy and/or HIV-encephalitis) as compared to patients lacking these features, a small decrease in neuronal density was noted but this difference did not reach the level of statistical significance (P = 0.16). In the superior parietal lobule (area 7) of AIDS brains, no loss of nerve cells was noted. AIDS patients with progressive dementia and brains with HIV-specific neuropathology showed no difference in neuronal densities as compared to those without such features. We conclude that the fronto-orbital cortex, in contrast to the parietal cortex, is mainly damaged in AIDS brains. Neuronal loss was not significantly correlated with development of dementing symptoms and of HIV-specific neuropathology. PMID- 8442410 TI - Neuropathologic aspects of hypothermic circulatory arrest in newborn dogs. AB - A model of hypothermic circulatory arrest with recovery has been developed in the newborn dog. Eleven puppies were anesthetized with halothane, paralyzed and artificially ventilated with 70% nitrous oxide -30% oxygen to paO2 > 60 mm Hg, paCO2 = 33-42 mm Hg and pHa = 7.35-7.42. Animals were surface cooled to 20 degrees C, following which cardiac arrest was effected with i.v. KCl. Dogs remained asystolic without ventilation for 1.0, 1.5 or 1.75. Resuscitation was accomplished with closed-chest compression, mechanical ventilation, i.v. epinephrine and NaHCO3, and rewarming to 37 degrees C. Thereafter, the puppies were allowed to recover from anesthesia and maintained for either 18-22 h (n = 9) or 72 h (n = 2), at which time they underwent perfusion-fixation of their brains for pathologic analysis. Of the total, four out of four puppies arrested for 1.0 h exhibited no brain damage, including one recovered for 72 h; whereas one out of three and four out of four puppies arrested for 1.5 and 1.75 h, respectively, showed brain damage predominantly of the cerebral cortex but also of the basal ganglia and amygdaloid nucleus. The hippocampus was spared, even in a 1.75-h arrested animal which was maintained for 72 h. No differences in pre- or post arrest systemic blood pressure, heart rate, or acid-base balance were observed between the brain damaged and undamaged animals except for the single damaged animal arrested for 1.5 h, for which the blood pressure prior to cardiac arrest and during recovery was the lowest of all survivors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8442411 TI - Desmoplastic ganglioglioma: report of two non-infantile cases. AB - Two supratentorial desmoplastic gangliogliomas arising in a 15-year-old boy and a 25-year-old man are reported. Both tumors reached the brain surface and exhibited large cysts. They showed intense desmoplasia and tumor cells of astrocytic and ganglionic differentiation. In one case the ganglionic nature was only demonstrable by immunohistochemistry. Such neoplasms can no longer be regarded as exclusively infantile brain tumors. PMID- 8442412 TI - Structure and pathogenesis of cortical nodules induced by prenatal X-irradiation in the rat. AB - Segmentation of the cerebral cortex with formation of nodules, predominating in the upper cortical levels, was found in the rat after 200 cGy X-ray exposure at embryonic days 15, 17 or 19. Nodules were composed of pyramidal and nonpyramidal neurons occupying normal positions at different levels of the cerebral cortex as revealed with parvalbumin and calbindin D-28k immunocytochemistry. The nodules, which were large in animals irradiated at embryonic day 15 but reduced to groups of a few cells in rats irradiated at embryonic day 19, were separated by low cell density zones. Autoradiographic studies using tritiated methylthymidine injections given to pregnant irradiated rats at different days of gestation further demonstrated a preserved inside-out gradient of cortical neurogenesis in this cortical malformation. Morphological studies of irradiated embryos disclosed that groups of dead cells were separated by patches of preserved cells in the germinal layer 6 h after irradiation. Columns of migrating neuroblasts separated by low cell density zones were seen 24 h later. These features suggest that cortical nodules observed after prenatal X-irradiation were the result of multifocal cell death in vulnerable (at the moment of X-ray exposure) proliferative units of the germinal neuroepithelium, combined with normal neurogenesis and migration of neuroblasts from the preserved germinal zones. These findings also suggest that cell proliferation is not uniform through the germinal layer but occurs synchronously in alternate proliferative units. These proliferative units probably co-generate pyramidal and nonpyramidal cells. PMID- 8442413 TI - Diffuse Lewy body disease with immediate post-partum onset. AB - A previously healthy 27 years-old woman developed psychotic depression and parkinsonism shortly after delivery of her first child. Her neuropsychiatric symptoms progressed to dementia and she died 5 years after onset. Diffuse Lewy body disease was found at autopsy. This case is unusual because of the early age of onset and the abrupt development of symptoms following pregnancy. PMID- 8442414 TI - Selective death of immature neurons in methylmalonic acidemia of the neonate: a case report. AB - We report the clinical and post-mortem findings in a 4-day-old female infant with methylmalonic acidemia (MMA) prematurely delivered at 36 weeks gestation. Complementation analysis revealed a defect in methylmalonyl-CoA mutase apoenzyme activity. There was selective cell death of immature neurons involving germinal matrix, migrating neuroblasts, and both external and internal granular cell layers of the cerebellum and dentate gyrus of the hippocampus. Karyorrhexis was also seen in the lymphoid follicles of spleen, lymph nodes and in the thymus. Additionally, the spinal nerve roots demonstrated optically empty spaces in their myelin sheaths due to adaxonal separation of their myelin lamellae. PMID- 8442415 TI - Symmetrical neurofibroma with Schwann cell predominance and focal formation of microneurinomas. AB - A case of symmetrical neurofibroma with onion bulbs in various stages of development and progression to microneurinomas is presented. Immunohistochemistry with differentiation and growth factor markers as well as electron microscopy showed a Schwann cell origin of the concentrically arranged cells. The onion bulbs differed from those of hypertrophic neuropathy by their more compact structure. A partial expression of cellular proliferation markers in the onion bulbs was consistent with a multifocal proliferative activity, confirming the neoplastic nature of the lesion. PMID- 8442416 TI - Averages of sound pressure levels and mean fundamental frequencies of speech in relation to phonetograms: comparison of nonorganic dysphonia patients before and after therapy. AB - The interdependence of changes in mean fundamental frequency and mean phonatory sound level, before and after voice treatment, was studied in 22 female and 11 male patients suffering from nonorganic dysphonia. All patients read continuous texts at three different vocal loudness levels, and also while being exposed to a filtered noise. After the reading sessions, phonetograms were recorded. The female patients achieved a higher mean sound level during the speech test after therapy. By contrast, the male patients increased their mean fundamental frequencies less during noise exposure after therapy, while the female patients retained essentially the same mean fundamental frequencies afterwards. The female patients produced a significantly higher upper phonetogram contour after therapy, whereas the male patients lowered their lower phonetogram contour. PMID- 8442417 TI - Growth of evoked potential amplitude in neonatal chicks exposed to intense sound. AB - The recovery of auditory function at selected intervals following exposure to a 0.9 kHz tone for 48 h at 120 dB SPL is described in neonatal chicks. Evoked potentials recorded from the nucleus magnocellularis were used to measure threshold sensitivity and peak-to-peak response amplitude as a function of stimulus intensity. The relation between evoked-response amplitude and stimulus intensity was nearly linear in control animals. However, at 10 days post exposure, the evoked response in mid-range frequencies showed a severe threshold shift and an abnormally rapid growth in amplitude. At 3 days post exposure, the rate of growth was nearly identical to that measured in control animals and threshold sensitivity showed considerable recovery. Current theories of amplitude intensity growth and studies of basilar papilla damage and repair following intense sound exposure were applied in the analysis of these results. PMID- 8442418 TI - The effect of endocochlear potential suppression upon susceptibility to acoustic trauma. AB - In the present study we investigated the influence of decreased endocochlear potential (EP) on acoustic trauma. Guinea pigs with decreased EP following i.v. administration of furosemide (FUR) and normal EP given physiological saline solution (PSS) i.v. instead of FUR were exposed to 2 kHz pure tone ranging from 110 to 130 dB SPL for 5 min. The input-output curves of the compound action potential (CAP) before acoustic overstimulation were compared with those at 2 h after the exposure. In 125 and 130 dB SPL exposure there was no difference in threshold shift between the FUR and PSS groups. In 115 and 120 dB SPL exposure, however, the threshold shift of the FUR group was significantly smaller than that of the PSS group. There was no significant difference between the two groups in 110 dB SPL exposure. These results indicate that the threshold shift of the CAP is mainly due to excessive vibration of the basilar membrane in the greater stimulus groups (125-130 dB SPL) but that the energy exhaustion of the hair cells to a certain extent participates in the threshold shift when the stimulus is milder (115-120 dB SPL). It is concluded that susceptibility to acoustic trauma of a milder intensity (115-120 dB SPL) is reduced when the energy consumption rate of the organ of Corti is decreased by EP suppression. PMID- 8442419 TI - Jongkees' formula re-evaluated: order effects in the response to alternate binaural bithermal caloric stimulation using closed-loop irrigation. AB - Normal limits for the response to caloric irrigation typically are specified as percentage of reduced vestibular response (RVR) and directional preponderance (DP). These measures are calculated using Jongkees' formula without regard to which ear is stimulated first. To assess the influence of the order in which the caloric stimuli are delivered we reviewed the responses to closed loop caloric irrigation of two groups of normal subjects and a group of unselected patients. Results indicated a consistent declining trend in response from the first caloric administration to the last administration in all groups and subgroups except in male patients over 60 years of age. Consequently, a significant bias in RVR was observed. Specifically, with the order of irrigation left cold, right cold, left warm, right warm, the mean percentage RVR for both the patients and control subjects was about a 5% right RVR. The bias resulted in right-sided unilateral hypofunction being diagnosed 2.4 times more often than left-sided hypofunction in patients aged 16-59. Our results differ from the previous literature that describes the effect of order on the response to caloric irrigation; this discrepancy may be related to our use of a closed-loop system for caloric irrigation. We conclude that vestibular laboratories should account for the effect of order in their patients' responses to caloric stimulation. We offer suggestions on how Jongkees' formula can be corrected for the effect of order. PMID- 8442420 TI - Auditory evoked potentials in cats with neonatal high frequency hearing loss. Evidence of abnormal frequency representation in the midbrain. AB - We have recorded auditory evoked potentials, of both neurogenic and myogenic origin, in cats having neonatal high frequency cochlear hearing loss. Using frequency specific stimuli (tone pips) and by measuring responses near to threshold, we have probed tonotopic (or cochleotopic) representation within the brainstem-midbrain auditory pathway. At stimulus frequencies corresponding to the high frequency cut-off of the cats' audiograms we have observed enhanced amplitudes of both auditory brainstem evoked responses (ABR) and postauricular myogenic (PAM) potentials. We interpret our findings as evidence of a larger than normal population of neurons tuned to this frequency region. We suggest that such abnormal frequency representation results from a long-term sensory deficit caused by lesions to the basal, high frequency region of the cochleas. PMID- 8442421 TI - Audiological assessment of eleven congenital hypothyroid infants before and after treatment. AB - Eleven congenital hypothyroid newborns were consecutively referred for audiological evaluation before any treatment. Evoked otoacoustic emissions were present bilaterally in 9 newborns. These results suggest the normality outer hair cells and contrast with results obtained in experimental studies. The auditory brainstem responses in 6 newborns showed a prolonged wave I, as previously reported by other authors. At 9 to 12 months of age, all children treated had evoked otoacoustic emissions in at least one ear. In 9 cases, the auditory threshold was normal (equal to or below 20 dB) as determined by behavioural tests. PMID- 8442422 TI - Cholera toxin B-HRP and wheat germ agglutinin-HRP tracing of tensor tympani muscle motoneurons and processes in rabbits. AB - The brain stem position, organization and number of motoneurons innervating the rabbit tensor tympani muscle (TTM) were determined by retrograde axonal transport of cholera toxin B/horseradish peroxidase conjugate (CTB-HRP) and wheat germ agglutinin HRP conjugate (WGA-HRP) tracers. The synaptic input to the TTM motoneurons was examined with WGA-HRP. The results show the motoneurons of the TTM to be localized in a cluster ventro-lateral to the outer margin of the ipsilateral trigeminal motor nucleus (VMN) and dorso-lateral to the superior olive. The number of labeled cells was greater in the combined CTB-HRP/WGA-HRP injected cases. The TTM motoneurons were triangular and elongated in shape and smaller than those of the VMN. An extensive network of dendritic branches was present ventro-laterally in the vicinity of the superior olive. Similar, but less extensive collections of dendritic processes were observed to course dorso medially, rostrally and caudally. Axons were observed to project first dorsally or laterally, towards the trigeminal motor root, then after a sharp turn coursed ventrally within the trigeminal motor root (VMR). Transneuronal transport of the WGA-HRP was not accomplished in any preparation, suggesting among other things, system or species differences in the effectiveness of the WGA-HRP conjugate as a transynaptic tracer. It is concluded that the TTM acoustic reflex in rabbits and other mammals, its threshold, prolonged contraction capacity, and its influence on middle ear sound transmission may be related to its demonstrated extensive synaptic field in the reflex chain, particularly in the area of the superior olive, while its many other physiological functions may be made possible by the number, location, and multi-dimensional orientation of its motoneurons and dendrites. PMID- 8442423 TI - The effect of topical application of vasodilating agents on cochlear electrophysiology. AB - The aim of this investigation was to study whether increased blood flow has beneficial effects on the ear or whether it is damaging to the auditory function, expressed as the auditory gross neural response. Four vasodilating agents were examined after topical application with respect to their influence on cochlear blood flow (CBF), blood pressure, and auditory function in the normal guinea pig. CBF was recorded with laser-Doppler. The drugs used were sodium nitroprusside, hydralazine, nicotinic acid and histamine. Sodium nitroprusside and hydralazine increased CBF and induced concentration dependent loss of auditory function. Neither nicotinic acid nor histamine had any effect on CBF. Nicotinic acid had varying effects: in some cases a negative influence on threshold shifts was seen, and in others a positive one. In most cases histamine caused improvement of the auditory function. The data indicate that topical administration of drugs to the inner ear is effective to influence both CBF and auditory function. PMID- 8442424 TI - Experimental pressure induced rupture of the tympanic membrane in man. AB - The size of the overpressure in the ear canal which causes rupture of the tympanic membrane (TM) in man (rupture pressure, RP) was determined in 90 subjects 7-112 h post mortem in connection with the autopsy. The equipment allowed an overpressure in the ear canal to be applied either gradually or suddenly. In 144 normal TMs it was demonstrated that the tensile strength of the TM increases post mortem. Corrected to the time 0 post mortem, RP of normal TMs ranged 0.5-2.1 kp/cm2, median 1.2 kp/cm2. It was found to be correlated to the age of the patient, i.e. RP decreased with increasing age. No correlation was found between RP and the application speed of the overpressure. Ninety-nine percent of the ruptures were localized to the pars tensa (63% to the anterior part of this structure) and typically had the shape of a minor tear. The RP of 23 TMs with atrophic scars was significantly lower, 0.3-0.8 kp/cm2, and the rupture typically had the shape of a larger defect. The results of this study indicate large intersubject variability of the tensile strength of the human TM. Some individuals are at increased risk of TM rupture at minor overpressures in the ear canal (e.g. during certain watersports, such as diving) which may carry medicolegal implications. PMID- 8442425 TI - Growth factors during proliferation of the middle ear mucosa. AB - The presence of growth factors during otitis media with effusion (OME), induced by antigenic stimulation of the middle ear, was explored in guinea pigs. There was a significant increase in heparin-binding proliferative activity detected in mucosal tissue. This heparin-binding activity was identified as basic fibroblast growth factor (FGF) using several criteria. First, the majority of this activity was eluted from heparin-Sepharose gels with 1.3-1.8 M NaCl, consistent with basic FGF. Second, these fractions are potent stimulators of endothelial cell proliferation, characteristic of basic FGF. Third, the fractions contain basic FGF-like immunoreactivity based on radioimmunoassay. Finally, Western blotting of tissue extracts reveals the presence of an 18 kDa protein that is indistinguishable from basic FGF. We conclude that basic FGF plays a major role in the proliferation of the middle ear mucosa during OME. PMID- 8442426 TI - Eustachian tube function in the ferret. AB - The role of viral upper respiratory tract infections (URI) in the pathogenesis of otitis media (OM) may be related to Eustachian tube (ET) dysfunction. Preliminary experimental evidence suggests that the ferret may be an appropriate animal for modeling of pathophysiologic process related to URI's and ET dysfunction. In an effort to determine the applicability of this animal model, normal ET function was evaluated in 10 ferrets using the inflation-deflation and forced-response testing protocols. The results indicate that the ET of the ferret functions as a small-scale version of its rhesus monkey and human counterparts. The ET-middle ear (ME) system could maintain applied positive and negative ME pressures in all instances. Nearly complete swallow-induced pressure equilibrations were demonstrated in all ears tested. Elevated passive function parameters suggested a small tubal lumen. The efficiency of the tubal dilatory mechanism as expressed by the normalizing calculation (R0/RA) was shown to be quite similar to that in primates and man. These findings suggest that the ferret's ET functions in a manner similar to humans and is, therefore, an appropriate animal to study the pathogenesis of otitis media in the context of ET dysfunction. PMID- 8442427 TI - Cytological and histological changes in the middle ear after inoculation of influenza A virus. AB - Experimental otitis media induced in the chinchilla by inoculation of influenza A virus into the middle ear resulted in capillary engorgement, subepithelial hemorrhage, tissue edema and acute inflammatory cell infiltration. Quantitative morphometric measurements were made for 28 days. Ciliated cells appeared to be the primary target of this strain of influenza virus and demonstrated the greatest degree of damage. Three weeks were required to restore the ciliated epithelium in the tubotympanum to normal levels. PMID- 8442428 TI - Micro-ecology of the nasopharyngeal bacterial flora in otitis-prone and non otitis-prone children. AB - The quantitative bacteriology of the adenoid was studied in otitis-prone and non otitis-prone children. alpha-hemolytic Streptococci (Viridans Streptococci) appeared to be predominant normal flora in the healthy nasopharynx. There was a decrease in alpha-hemolytic Streptococci in the otitis-prone child compared to the non-otitis-prone child. Concomitantly, there appears to be an increase in both nontypable Haemophilus influenzae (NTHI) and S. pneumoniae in the nasopharyngeal flora in the otitis-prone child. The mechanisms responsible for this alteration of the micro-ecology of bacteria of the nasopharynx may be related, in part, to factors that alter mucociliary function. These factors could be viral infection, allergy, local and systemic immunological deficiency and the indiscriminate use of antibiotics. An understanding of the relationship between the normal flora and the potential pathogens may be important in the understanding of both the pathogenesis of otitis media (OM) and possibly the treatment of this disease entity. PMID- 8442429 TI - The embryologic development of the human anterior nasal aperture. AB - During the final period of embryogenesis, the nasal pit is clearly apparent in the Carnegie stage 15 embryo, and extends backwards into the oral cavity forming the nasal sac. In the stage 19 embryo of about 7 weeks, abundant epithelial proliferation into the lumen forms the nasal meatal plug. The complete recanalization of this meatal plug occurs in the 16-17 week fetus, and not in the 24th week of fetal life as is generally accepted in textbooks on human embryology. The findings of the present study of the embryology of the anterior nares can well explain the anomalies of the human anterior nares aperture. PMID- 8442430 TI - Ultrastructural changes of the basement membrane zone in benign lesions of the vocal folds. AB - The basement membrane zone (BMZ) of the epithelium of the vocal folds was investigated electron microscopically in 10 patients suffering from various benign lesions and in 3 controls. Various defects were observed: a thickening by deposition of electron dense material, a loss of normal architecture, and a near absence of normal hemidesmosomes and anchoring fibers. Beside these previously reported phenomena, many vesicles carrying electron dense material were found near the plasma membrane. The vesicles were observed at various stages of fusion with the plasma membrane, on the other side of which their content was discharged. In the cytoplasm an increase of mitochondria was seen. The amount of condensed chromatin decreased while the nucleoli increased in comparison with the controls. These observations are suggestive of a hyperactivity of the basal cells of the epithelium in response to vibratory stress. PMID- 8442431 TI - Serum markers of type I collagen formation and degradation in metabolic bone disease: correlation with bone histomorphometry. AB - Type I collagen makes up more than 90% of bone matrix. Therefore, analysis of antigens related to collagen formation and degradation in bone should provide good and specific estimates of both bone resorption and bone formation rates. In this study we measured serum levels of the pyridinoline cross-linked telopeptide domain of type I collagen (ICTP) as a marker of bone resorption and serum carboxy terminal propeptide of type I procollagen (PICP) as a marker of bone formation. Serum levels of the two antigens were correlated to histomorphometric indices of bone resorption and bone formation calculated from iliac crest bone biopsies in a group of 18 individuals with high- and low-turnover bone disease (myxedema, primary hyperparathyroidism, and thyrotoxicosis). After logarithmic transformation the regression of S-ICTP on volume-referent resorption rate (BRs/R/BV) was significant (r = 0.61, p < 0.01, SEM/Y = 56%). S-ICTP also showed a significant regression on the volume-referent cancellous bone balance (r = 0.45, p < 0.05, SEM/Y = 412%). S-PICP was significantly correlated to the mineral appositional rate (r = 0.53, p < 0.05) and volume-referent bone formation rate (r = 0.61, p < 0.01, SEM/Y = 48%). The correlation to bone turnover as expressed in the activation frequency was also highly significant (r = 0.61, p < 0.01, SEM/Y = 51%). No significant correlation with wall thickness or bone balance was demonstrable per remodeling cycle. Thus, assays employing antigens that reflect collagen formation and degradation are useful instruments for the evaluation of rates of bone remodeling in metabolic bone disease. PMID- 8442433 TI - Tumor necrosis factors alpha and beta can stimulate bone resorption in cultured mouse calvariae by a prostaglandin-independent mechanism. AB - Human recombinant tumor necrosis factors alpha and beta (TNF-alpha and TNF-beta), at and above 1 ng/ml (approximately equal to 70 pM), caused a dose- and time dependent enhancement of 45Ca release from neonatal mouse calvarial bones in vitro. In addition, TNF-alpha and TNF-beta (3-100 ng/ml) caused a dose-dependent stimulation of prostaglandin E2 (PGE2) formation in the calvarial bones. TNF alpha also enhanced the biosynthesis of PGI2, as assessed by analysis of the stable breakdown product 6-keto-PGF1 alpha. The stimulatory actions of TNF-alpha and TNF-beta on PGE2 formation was maximal at 12 h. Indomethacin, flurbiprofen, and meclofenamic acid, three structurally unrelated nonsteroidal antiinflammatory drugs, abolished PGE2 biosynthesis induced by TNF-alpha and TNF-beta (100 ng/ml). The 45Ca release stimulated by TNF-alpha and TNF-beta (100 ng/ml), however, was only slightly reduced by indomethacin, flurbiprofen, and meclofenamic acid. The partial inhibitory effect of indomethacin on 45Ca release was seen over a wide range of TNF-alpha concentrations, without affecting the concentration producing half-maximal stimulatory response. TNF-alpha and TNF-beta (100 ng/ml) stimulated bone matrix breakdown, as assessed by analysis of the release of 3H from bone prelabeled with [3H]proline. Also, the stimulatory effect of TNF-alpha and TNF beta on bone matrix degradation was partially reduced by indomethacin. Hydrocortisone (1 microM) and dexamethasone (0.1 microM) abolished TNF-alpha- and TNF-beta-induced production of PGE2. In contrast to the cyclooxygenase inhibitors, the corticosteroids did not affect the stimulatory action by the cytokines on 45Ca release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8442432 TI - Collagen crosslinks and mineral crystallinity in bone of patients with osteogenesis imperfecta. AB - In cortical bone samples from patients with osteogenesis imperfecta (OI), the concentrations of hydroxypyridinium cross-linking amino acids in collagen were measured by reversed-phase HPLC and the x-axis crystallinity of the apatite mineral phase was determined by x-ray diffraction. Bone samples from three patients with type I, nine patients with type III, and eight patients with type IV OI were analyzed and compared with human bone from nine controls. The concentration of the two chemical forms of the mature collagen crosslinking amino acids, hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP), and the ratio HP/LP were found to be alike in bone collagen of OI patients and healthy controls. However, the c-axis crystallinity of the apatite was found to be reduced in the type III and IV OI patients compared with controls. Regression analysis of crosslink concentrations and c-axis crystallinity in OI bones did not show any correlation. Therefore, collagen molecules deposited in the extracellular matrix of OI bone appear to fulfill the structural requirements for the action of the enzyme lysyl oxidase, such that a normal concentration of intermolecular crosslinks is formed compared with healthy bone. Consequently, crosslink formation and apatite crystal growth seem to be regulated independently in OI bone. PMID- 8442434 TI - A new method for vertebral fracture diagnosis. AB - A number of methods have been proposed for estimating the prevalence of vertebral fractures. Most methods are based on the distribution of normal vertebral dimensions in the population. However, these methods fail to identify a significant proportion (20-30% or more) of fractures documented on serial radiographs. This may occur because vertebral size varies between individuals as a result of differences in body size (and possibly other factors), and a normal range based on population reference data may be too large. In this paper, a new method is described for identifying vertebral fractures that are missed using diagnostic criteria based on vertebral dimension distributions of the population. This new method is based on calculating the average vertebral size, and statistical confidence limits, for the individual. The average vertebral size method was evaluated by testing its ability to identify incident fractures (which were identified from changes in dimensions compared to previous radiographs), using only the final film. The new method correctly identified most (81% of crush and 83% of wedge) incident fractures on the final radiograph. In contrast, criteria based on population distributions correctly identified only 53% of crush and 72% of wedge incident fractures. Using prospective data, prevalent fractures identified using both population-based and individual size-based criteria predicted the risk of incident fractures. Furthermore, incident fractures identified using both methods (population- and individual-based criteria) were associated with increased back pain. These data suggest that both types of prevalent deformities are important indicators of disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8442435 TI - Improved treatment of Paget's disease with dimethylaminohydroxypropylidene bisphosphonate. AB - A group of 89 patients with Paget's disease of bone were treated with different intravenous or oral doses of the nitrogen-containing bisphosphonate dimethylaminohydroxypropylidene bisphosphonate (dimethyl-APD). Biochemical remission was obtained in 82% of treatments, and in the rest a clear response was found. Oral dimethyl-APD was well tolerated, and a dose of 200 mg/day for 10 days was sufficient to induce remission in the majority of patients. The remission probability was 3 months for 50% of patients, and the recurrence-free period was 27 months. The remission probability as well as the recurrence-free period did not differ among oral and intravenous treatments or among patients who had never been treated with nitrogen-containing bisphosphonates and those who had received pamidronate in the past and were treated for a recurrence of the disease. Dimethyl-APD is a very effective bisphosphonate devoid of side effects, which given for a short period can induce long-lasting remissions in patients with Paget's disease of bone. PMID- 8442436 TI - Pre- and postmenopausal bone mineral density of the spine and proximal femur in Japanese women assessed by dual-energy x-ray absorptiometry: a cross-sectional study. AB - To investigate the influence of menopause on bone mineral density (BMD) of Japanese women, BMD of the spine and proximal femur was measured by dual-energy x ray absorptiometry (DXA) in 220 premenopausal and 166 postmenopausal Japanese women. The peak bone density of the spine in premenopausal women was detected between 35 and 39 years of age, and that of femur before 20. Thereafter spinal and femoral BMD showed a slight decrease, but they did not show a significant decrease until menopause or menstruation became irregular. Duration of substantial bone loss at lumbar spine continued for about 10 years after menopause, but that at the femur was much longer. To investigate the effect of early menopause on bone loss, postmenopausal women were divided into two groups according to the age at onset of menopause. The BMD of postmenopausal women whose menopause occurred before 50 was significantly less over the latter part of life than that of women whose menopause occurred after 50. These results suggest that bone loss is related to menopause or irregular menstruation rather than age per se, and early menopause should be recognized as one of the risk factors for involutional osteoporosis. PMID- 8442437 TI - Leukemia inhibitory factor inhibits osteoclastic resorption, growth, mineralization, and alkaline phosphatase activity in fetal mouse metacarpal bones in culture. AB - Leukemia inhibitory factor (LIF) has been reported to affect bone metabolism, but results are variable. We examined the effect of mouse recombinant LIF on osteoclastic resorption in fetal bone explants representing different stages of osteoclast development. In cultures of 17-day-old fetal mouse metacarpals in which only osteoclast progenitors and precursors are present, resorption (measured as 45Ca release) was significantly inhibited to 29.2% and to 96.6% in the presence of LIF 100 and 1000 U/ml, respectively. Histologic examination of the explants treated with 1000 U/ml of LIF confirmed the biochemical findings and showed that osteoclast progenitors and precursors remained in the periosteum and did not invade the mineralized matrix. In metacarpals of older fetuses (18- and 19-day-old) in which the mineralized cartilage has been invaded by mature osteoclasts, the inhibition of resorption by LIF (1000 U/ml) was 87.9 and 74.7%, respectively, the latter being significantly less than the inhibition observed in 17-day-old metacarpal cultures. The inhibitory effect of LIF was absent during concurrent administration of PTH or 1,25-(OH)2D3 and could be reversed by PTH. In addition, LIF was found to inhibit growth, mineralization, and alkaline phosphatase activity in metacarpals independently of osteoclastic resorption. These results suggest that LIF affects the development rather than the activity of osteoclasts, probably through an effect on the osteogenic cells. LIF may be an important endogenous regulator of bone metabolism. PMID- 8442438 TI - Changes in bone histomorphometry after long-term treatment with intermittent, cyclic etidronate for postmenopausal osteoporosis. AB - Intermittent, cyclic etidronate therapy (400 mg/day for 2 weeks followed by 13 weeks free from study drug administration) resulted in a significant increase in lumbar bone mineral content and a significant decrease in the rate of new vertebral fractures in patients with postmenopausal osteoporosis. To investigate the effect of the treatment on bone histomorphometry, transiliac crest bone biopsy samples were obtained in this study before treatment and after 60 and 150 weeks of treatment with either intermittent, cyclic etidronate (n = 33) or placebo (n = 33). After 60 weeks of etidronate therapy, significant decreases in activation frequency (from 0.55 to 0.09 year,-1 P < 0.01) and resorption depth (from 53.2 to 37.8 microns, P < 0.05) were observed, leading to a positive balance per remodeling cycle. In the placebo group, no significant changes were seen. The 150 week bone biopsy samples were suboptimal for analysis, probably as a result of a regional acceleratory phenomenon. Our results suggest that, as a result of reductions in both activation frequency and resorption depth, intermittent, cyclic etidronate therapy may protect the trabecular network against fortuitous perforations and thereby maintain the strength of the bony tissue. PMID- 8442439 TI - Rapid, divergent changes in spinal and forearm bone density following short-term intravenous treatment of Paget's disease with pamidronate disodium. AB - Intravenous disodium 3-amino-1-hydroxypropylidene-1,1-bisphosphonate pentahydrate (pamidronate disodium) was used to treat 39 patients (22 males and 17 females, age range 48-85 years) with symptomatic Paget's disease. Patients were stratified into three groups based on the biochemical severity of the disease as assessed by fasting urinary hydroxyproline excretion (HypE, mumol/liter GF, glomerular filtrate): group I (n = 23), HypE < 5.0, treated with 120 mg total dose over 2 or 4 days; group II (n = 6), 5.0 < or = HypE < or = 10.0, 180 mg over 3 or 6 days; and group III (n = 10), HypE > 10.0, 240 mg over 4 or 8 days. Bone mineral density (BMD) was measured before and 3 and 6 months following treatment in the spine (L1-4) using dual-energy x-ray absorptiometry and in the forearm at an ultradistal and a shaft site using single-photon absorptiometry. When groups I III were combined, nonpagetic and pagetic lumbar spinal BMD had both risen significantly at 3 months compared with the pretreatment values (p < 0.001). In each group, lumbar spinal BMD in pagetic vertebrae rose markedly by 3 months, with no further significant change at 6 months. The percentage rises in the three groups were not different from each other at 3 or 6 months. Nonpagetic lumbar spinal BMD followed a similar and significant trend but with a significantly smaller rise than for pagetic bone. (For the combined groups, nonpagetic BMD rose 5.1 +/- 1.1% SEM, above pretreatment at 6 months; pagetic BMD rose 17.8 +/- 1.6%: significance of comparison = p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8442440 TI - High-dose gestagens modulate bone resorption and formation and enhance estrogen induced endosteal bone formation in the ovariectomized mouse. AB - To determine if gestagens of two separate classes have differing skeletal actions, we studied the effects of pharmacologic doses of norethisterone acetate (NETA), a 19-nortestosterone, and megestrol acetate (MA), a 17 alpha hydroxyprogesterone, on bone formation and resorption in intact and in ovariectomized mice. In the same set of experiments, we also attempted to determine if these gestagens can alter the skeletal activity of 17 beta-estradiol (E2). Experimentally, the skeletons of 78 female BALB/c mice were prelabeled with [3H]tetracycline (3H-T). The animals were randomized to 13 groups of 6 mice each 3 days after the final 3H-T injection. Ovariectomies (OVX) were performed on 8 groups and sham operations (SO) on 5 groups. To study the skeletal effects of the gestagens, 4 groups each of the OVX and SO mice were treated with controlled release pellet implants calculated to deliver 80 or 250 micrograms of NETA or MA per day. To study gestagen interactions with E2, 3 groups of OVX mice were treated with either 40 micrograms/day of E2 or 40 micrograms/day of E2 plus 250 micrograms/day of NETA or MA. One group of OVX and one group of SO animals received placebo pellets. Fluorochrome labels were administered 10 and 11 and 3 and 4 days before sacrifice to allow histomorphometric evaluation of bone formation. At the end of the 60 day protocol, tibiae and thoracic vertebrae were removed and processed for quantitating the levels of bone resorption based on the amounts of 3H-T retained in the bones. The femora were fixed and embedded for comparison of diaphyseal bone histomorphometry, and the humeri and lumbar vertebrae were prepared for bone density determinations. Reflecting an increase in bone resorption, 3H-T levels in tibiae and vertebrae were decreased in placebo treated OVX animals compared to the placebo-treated SO group (p < 0.01). Treatment of both SO and OVX mice with NETA decreased bone resorption in a dose dependent manner, but MA had no significant effects on vertebral bone resorption and increased bone resorption in the tibiae (p < 0.01). E2 treatment of OVX mice reduced bone resorption, but there were no significant interactions between the E2 and gestagen treatments on resorptive activity. Based on bone histomorphometry of in vivo fluorochrome labels, both gestagens increased periosteal bone formation rates but had no effect on endosteal bone formation (BFRe). In contrast, E2 treatment of the OVX mice stimulated bone formation at the endosteal surface.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8442441 TI - Role of bone matrix in osteoclast recruitment in cultured fetal rat calvariae. AB - In cultured 19 day fetal rat calvaria, osteoclasts first appear after 48 h, more rapidly than with other cultured embryonic long bone rudiments. This may be because the calvarial osteoclast precursors are more differentiated or intramembraneous bone is a more powerful stimulus for osteoclast maturation than endochondral bone. To investigate this further, 19 day calvariae were stripped of their endocranial membranes, devoiding them of osteoclast precursors, and cocultured with the membranes or with other sources of these cells, such as bone marrow, fetal liver, spleen, and blood. There was similar recruitment of mature osteoclasts onto the surface of the "stripped" calvariae from the endocranial membranes and from the hematopoietic tissues after 48 h culture. Intact 19 day fetal calvariae were cultured with human recombinant granulocyte-macrophage colony-stimulating factor (hrGM-CSF) or with 1,25-dihydroxyvitamin D3, [1,25 (OH)2D3], each thought to influence different stages of osteoclast maturation. They stimulated osteoclast recruitment, although 1,25-(OH)2D3 was effective only in the first 24 h of culture. They also increased osteoclast recruitment from fetal liver onto stripped calvariae. When intact bones were cultured with hrGM CSF and 1,25-(OH)2D3 together, osteoclast number decreased but their area increased. Calvariae therefore appear to contain osteoclast precursors at earlier (GM-CSF-sensitive) and later [1,25-(OH)2D3-sensitive] stages. As recruitment onto stripped calvariae was similar whichever source of precursors was used, it is likely that calvarial bone matrix is an important influence on rapid osteoclast maturation in these bones in vitro. PMID- 8442442 TI - Clinton team works with drug companies to expand access, restrict costs. PMID- 8442443 TI - FDA finalizing policy statement on industry-supported activities. PMID- 8442444 TI - Unit-of-use packaging to remain optional for now. PMID- 8442445 TI - Panel recommends limits on alcohol content of nonprescription products. FDA Over The-Counter Drugs Advisory Committee. PMID- 8442446 TI - CPSC revises stance on waivers for child-resistant packaging, finds aversive agents of limited value. PMID- 8442447 TI - Hospital will hire HIV-infected pharmacist. PMID- 8442448 TI - Electronic processing of Medicare claims. PMID- 8442449 TI - Guidelines for use of pneumatic tube systems. PMID- 8442450 TI - How to be an effective clerkship or internship preceptor. PMID- 8442451 TI - Steering pharmacy students to hospital practice. PMID- 8442452 TI - Ingredient labeling of prescription drug products. PMID- 8442453 TI - Outpatient compliance with zidovudine therapy in French Polynesia. PMID- 8442454 TI - IV tubing and bag change policies for pediatric patients. PMID- 8442455 TI - Lessons learned from promoting a cost-effective agent. PMID- 8442456 TI - Physician use of patient profiles. PMID- 8442457 TI - Filgrastim doses should not be standardized for pediatric patients. PMID- 8442458 TI - Expired drugs are not dead drugs. PMID- 8442459 TI - Expired drugs are not dead drugs. PMID- 8442460 TI - Clarifications to news story on certifiers. PMID- 8442461 TI - Association of antineoplastic drug handling with acute adverse effects in pharmacy personnel. AB - The relationship between occupational exposure to antineoplastic drugs and the presence of acute symptoms of exposure was investigated by questionnaire. Data were derived from a questionnaire distributed to 8566 pharmacists, pharmacy technicians, nurses, and nurse aids at 57 member institutions of the National Surgical Adjuvant Breast and Bowel Project nationwide. Of the 4659 respondents (54%), 1057 were pharmacists or pharmacy technicians; after exclusions, the sample size was 738. Data were collected on four handling activities: mixing of antineoplastic drugs, administering these drugs, cleaning up spills, and handling patient excreta. Information on mixing was divided into dose, duration, use of protection, and reported skin contact. Respondents indicated which of 27 acute symptoms they had experienced during the past three months. Handling of antineoplastics was associated with a small but significant increase in the number of symptoms compared with controls; reported skin contact was the most important predictor of symptoms. The number of doses handled and the extent of protection were significantly associated with the number of symptoms, but their effect was not independent of that of skin contact. Body mass was significantly associated with the number of symptoms in women but not men. Pharmacists and technicians who handle antineoplastic drugs reported more symptoms associated with exposure than did those who do not handle such agents. All available protective measures should be used. PMID- 8442462 TI - Justification of a pharmacy intravenous admixture service in an Australian hospital. AB - The time and cost of i.v. admixture preparation by hospital pharmacy staff members in an established admixture unit was compared with that by nurses working on wards. The preparation time of antimicrobial admixtures was determined by using a stopwatch. The total cost of preparing an admixture by pharmacy and nursing staff was calculated by combining the respective labor costs (preparation time x average salary rates weighted for overtime) with the cost of disposable items. The mean +/- S.D. time for admixture preparation in the pharmacy was 3.38 +/- 0.38 minutes, whereas preparation by nurses required 14.37 +/- 1.55 minutes. The mean +/- S.D. total cost (in Australian dollars) of admixture preparation was $1.42 +/- 0.34 per dose, and $4.59 +/- 0.46 per dose, respectively. Centralization of admixture preparation would reduce the time required by 18.32 hours for every 100 admixtures prepared, equivalent to an annual cost avoidance of $112,420 for every 100 admixtures prepared each day. Centralizing the preparation of i.v. admixtures in a hospital pharmacy resulted in significant time savings and cost avoidance. PMID- 8442463 TI - Continued cost justification of an operating room satellite pharmacy. AB - Cost justification for the establishment and continued operation of an operating room satellite pharmacy is described. Establishment of an operating room satellite pharmacy can be justified based on the need to recover lost revenue, regulate controlled substances, monitor inventory, and enhance communication between operating room personnel and the department of pharmacy. At a 510-bed community hospital, an internal audit performed before the satellite pharmacy was opened revealed an average loss of $14.53 in drug charges per surgical procedure; 16 months after the pharmacy opened, changes in the way drugs are distributed to the departments of surgery and anesthesia has resulted in a decrease in this loss to $9.61, or a 34% improvement. To regulate controlled substances, the pharmacy attaches a drug-use log to each dispensing kit, which has resulted in 98% agreement between recorded administration of controlled substances and actual amounts signed out and ultimately returned. Recommendations made by the department of pharmacy regarding the use of high-cost drugs during surgery has resulted in an annual savings of more than $100,000, and improvements in drug packaging reduced, and in some cases eliminated, wastage. Direct contact between operating room personnel and pharmacists has fostered discussions regarding cost effective application of pharmacotherapy, and the potential for cost savings is substantial. Although the remaining loss of $9.61 per case must still be addressed, considerable progress has been made in a relatively short period of time. The satellite pharmacy in the operating room has led to increased revenue recovery, improved regulation of controlled substances and monitoring of drug inventory, and better communication among the involved personnel. PMID- 8442464 TI - Stability of cyclosporine with magnesium sulfate in 5% dextrose injection. AB - The compatibility and stability of cyclosporine with magnesium sulfate in 5% dextrose injection was studied. Cyclosporine solution 50 mg/mL was added to each of three glass bottles containing magnesium sulfate injection and 5% dextrose injection; final theoretical concentrations of cyclosporine and magnesium sulfate were 2.0 mg/mL and 30 mg/mL, respectively. The samples were stored under fluorescent lighting at controlled room temperature (24 +/- 2.4 degrees C). At 6, 12, 24, and 36 hours each solution was visually inspected under normal lighting against a white and black background for color change, haze, or precipitation. Samples were assayed in duplicate for cyclosporine concentration by using a stability-indicating high-performance liquid chromatographic method. Turbidity occurred immediately after mixing but resolved in approximately 30 seconds. No other changes in clarity or color were noted. The admixtures retained > 90% of initial cyclosporine concentration for six hours, and there were no significant differences in mean cyclosporine concentrations among the individual samples. Cyclosporine 2.0 mg/mL added to magnesium sulfate 30 mg/mL in 5% dextrose injection was stable for six hours when stored in glass bottles at 24 degrees C under fluorescent lighting. PMID- 8442465 TI - Stability of midazolam hydrochloride in extemporaneously prepared flavored gelatin. AB - The stability of midazolam hydrochloride in flavored gelatin was evaluated after storage at 4 degrees C for 14 days and at -20 degrees C for 28 days. A flavored liquid gelatin mixture was prepared and mixed with midazolam hydrochloride injection in final concentrations of midazolam 1 and 2 mg/mL. Gelatin cups containing 5 and 15 mg of midazolam were prepared by measuring appropriate volumes of the gelatin stock solutions and were stored in a refrigerator at 4 degrees C or in a freezer at -20 degrees C. Immediately after preparation and at 7 and 14 days, three refrigerated and three frozen gelatin samples of each midazolam concentration were visually inspected, tested for pH, and assayed for midazolam concentration by high-performance liquid chromatography. The frozen gelatin samples were also evaluated at 21 and 28 days; three whole and three partial gelatin samples were assayed for midazolam content to determine the uniformity of drug distribution within each sample. All samples maintained greater than 96% of the initial midazolam concentration throughout the study. There was no appreciable change in color, odor, or pH. The midazolam content of the gelatin in the cups was uniform. An extemporaneously compounded preparation of midazolam hydrochloride in flavored gelatin was stable when stored for 14 days at 4 degrees C and for 28 days at -20 degrees C. Distribution of midazolam hydrochloride in the gelatin was uniform. PMID- 8442466 TI - Justifying an information system. AB - A four-step model for the hospital pharmacist to use in justifying a computerized information system is described. In the first step, costs are identified and analyzed. Both the costs and the advantages of the existing system are evaluated. A request for information and a request for proposal are prepared and sent to vendors, who return estimates of hardware, software, and support costs. Costs can then be merged and analyzed as one-time costs, recurring annual costs, and total costs annualized over five years. In step 2, benefits are identified and analyzed. Tangible economic benefits are those that directly reduce or avoid costs or directly enhance revenues and can be measured in dollars. Intangible economic benefits are realized through a reduction in overhead and reallocation of labor and are less easily measured in dollars. Noneconomic benefits, some involving quality-of-care issues, can also be used in the justification. Step 3 consists of a formal risk assessment in which the project is broken into categories for which specific questions are answered by assigning a risk factor. In step 4, both costs and benefits are subjected to a financial analysis, the object of which is to maximize the return on investment to the institution from the capital being requested. Calculations include return on investment based on the net present value of money, internal rate of return, payback period, and profitability index. A well-designed justification for an information system not only identifies the costs, risks, and benefits but also presents a plan of action for realizing the benefits. PMID- 8442467 TI - Pharmacy involvement in a surgery preadmission program. PMID- 8442468 TI - Instability of aqueous captopril solutions. PMID- 8442469 TI - ASHP technical assistance bulletin on use of controlled substances in organized health care settings. PMID- 8442470 TI - ASHP technical assistance bulletin on the pharmacist's role in immunization. AB - Pharmacists can play an important role in health promotion and disease prevention by advocating proper immunization. To do so, pharmacists must actively practice and promote preventive medicine. As primary contact persons in the health care system, pharmacists have the opportunity to screen and counsel their patients to help protect them from preventable infections. PMID- 8442471 TI - ASHP guidelines on pharmacist-conducted patient counseling. PMID- 8442472 TI - When other words fail. PMID- 8442473 TI - Doomed to deafness? PMID- 8442474 TI - The genie in the bottle. PMID- 8442475 TI - Billie's eyes. PMID- 8442476 TI - How to recognize and rotate an occiput posterior fetus. PMID- 8442477 TI - Update: guidelines for treating hypertension. PMID- 8442478 TI - Are you ready for video thoracoscopy? PMID- 8442479 TI - Recognizing child abuse. PMID- 8442480 TI - Self-scheduling: two success stories. No more short staffing. PMID- 8442481 TI - Nurses as house staff. PMID- 8442482 TI - Self-scheduling: two success stories. The art of the deal. PMID- 8442483 TI - Using ETCO2 to confirm endotracheal-tube placement. PMID- 8442484 TI - Pediatric nursing: preserving a national treasure. PMID- 8442485 TI - An HIV-infected pharmacist must be employed without restraints to his practice. PMID- 8442486 TI - Speaking of sex. PMID- 8442487 TI - Replacing a chest-tube drainage-collection device. PMID- 8442488 TI - Combination antibiotic supplementation of corneal storage medium. AB - Gram-positive cocci frequently contaminate donor corneal tissue and represent the most common cause of postkeratoplasty endophthalmitis. Although gentamicin is currently added to corneal storage medium in an effort to decrease bacterial contamination of donor tissue, it has poor or variable in vitro activity against many strains of streptococci and staphylococci. To investigate whether the antibiotic supplementation of corneal storage media could be improved, we surveyed 11 antibiotics for antimicrobial efficacy under simulated storage conditions against gentamicin-resistant strains of Staphylococcus aureus, S. epidermidis, Streptococcus pneumoniae, and St. viridans. All antibiotics showed markedly reduced activity at 4 C as compared to their predicted activity at 37 C. Bactericidal activity of streptomycin and tobramycin was enhanced by preceding 4 C storage with a three-hour period at room temperature (23 C). Under these conditions, streptomycin showed the best antimicrobial activity of the 11 antibiotics tested. Addition of gentamicin to streptomycin resulted in further improvement of activity against S. aureus and S. epidermidis, whereas the addition of penicillin G to streptomycin enhanced the activity against St. viridans. Optimal antibiotic activity (99% or more killing) against all four isolates of gentamicin-resistant gram-positive cocci was best achieved with the combination of gentamicin, streptomycin, and penicillin G, coupled with a three hour period at room temperature before 4 C storage. PMID- 8442489 TI - Bacterial and fungal endophthalmitis after penetrating keratoplasty. AB - We analyzed 1,010 consecutive penetrating keratoplasties to determine the incidence of postoperative endophthalmitis, the frequency of positive donor rim cultures, and whether a correlation between these two factors exists. There were three cases of bacterial endophthalmitis, all caused by streptococci, and one case of Candida albicans endophthalmitis. In all cases except one case of streptococcal endophthalmitis, the same organism was cultured from the donor rim. We cultured 138 organisms from 128 of 932 donor rims (14%). A remarkable percentage of gram-positive organisms were resistant to gentamicin, the only antibiotic contained in corneal storage media. On the basis of our data and previously published data, we believe that donor material is frequently the source of microorganisms in endophthalmitis after penetrating keratoplasty. PMID- 8442490 TI - Results of penetrating keratoplasty in aniridia. AB - Eight aniridic patients with bilateral corneal scarring, vascularization, or edema underwent corneal transplantation in one or both eyes (11 eyes). Follow-up ranged from eight months to 5 1/2 years (average, three years). Six of 11 eyes (55%) had at least a two-line improvement in visual acuity and eight of 11 (73%) had at least one line of improvement. Best-corrected visual acuity was 20/200 or worse in nine of 11 eyes (82%), however. Postoperative complications included whorl keratopathy, persistent epithelial defects, central subepithelial scarring, peripheral vascularization with pannus, and graft rejection. Glaucoma was well controlled medically but five of nine patients (56%) with preexisting glaucoma needed an increase in medication for intraocular pressure control. Graft rejection occurred in seven of 11 eyes (64%) and three of these eyes required repeat transplantation. PMID- 8442491 TI - Radial keratotomy for intolerable myopia after penetrating keratoplasty. AB - Radial keratotomy was used to treat intolerable myopia in nine patients aged 56 to 86 years who had previously undergone penetrating keratoplasty and intraocular lens placement. The degree of myopia ranged from -5.25 to -9.25 diopters spherical equivalent before radial keratotomy. An eight-cut radial keratotomy with either a 4.0- or 4.50-mm central clear zone was performed on all patients. One year after the radial keratotomy, the spherical equivalent ranged from -1.25 to +1.63 diopters, which rendered all patients spectacle tolerant. Endothelial cell counts done before and one year after radial keratotomy demonstrated no marked loss of endothelial cell density. No complications were seen as a result of the radial keratotomy. PMID- 8442492 TI - Risk of postoperative visual loss in advanced glaucoma. AB - The incidence of sudden visual loss after an intraocular procedure in patients with glaucoma and visual field defects has been disputed for over a century. We examined the risk of sudden visual loss associated with trabeculectomy in glaucoma patients with advanced visual field defects. Fifty-four filtering operations performed on 44 patients were reviewed. All patients had visual field defects encroaching on or splitting fixation, a visual acuity of 20/100 or better, and a follow-up period of at least two months. Thirty-one of the 54 preoperative visual fields (57%) disclosed a fixation-splitting defect. Sudden visual loss was not observed in any patient during the two-month postoperative period. These findings suggest that the incidence of sudden postoperative visual loss is lower than previously reported. PMID- 8442493 TI - Follow-up of angle-closure glaucoma suspects. AB - One hundred twenty-nine patients thought to be at risk for developing angle closure glaucoma underwent a baseline examination, which included gonioscopy, refraction, anterior chamber pachymetry, ultrasound biometry, and an angle closure provocative test. Patients were then followed up with no treatment. Mean follow-up was 2.7 years with a range up to six years. Twenty-five patients developed angle closure in at least one eye during the follow-up period, but in most (17 of the 25 patients), the angle closure was nonacute (that is, no clinical signs or symptoms and no increase in intraocular pressure). None of the test factors studied showed a high sensitivity or positive predictive accuracy in detecting the eyes that later developed angle closure. PMID- 8442494 TI - Intraocular pressure and retinal vascular changes during transient exposure to microgravity. AB - We measured intraocular pressures and retinal vascular diameters from 11 subjects during 20 seconds of microgravity produced by parabolic flight on board a KC-135 aircraft. Intraocular pressures increased 58% during parabolic flight compared to baseline values (19 +/- 1 mm Hg vs 12 +/- 1 mm Hg, respectively; P < .001). A 4% reduction in the caliber of retinal arteries was also noted during microgravity, but this change did not achieve statistical significance (7.8 +/- 0.3 pixels at zerogravity vs 8.1 +/- 0.3 pixels at 1g; P = .07). The increase in intraocular pressure and trend of arteries to constrict are thought to result from cephalad shifts in intravascular and extravascular body fluids as a result of the absence of the 1g hydrostatic gradient. The results of our study confirm that this fluid shift and its effects on the eye occur rapidly, within 20 seconds of exposure to microgravity. PMID- 8442495 TI - The relationship between static perimetry and the relative afferent pupillary defect. AB - This study was undertaken to understand better how damage to the anterior visual pathway may affect the relationship between the visual and pupillomotor systems. The relative afferent pupillary defect and the interocular difference in visual field mean deviation (determined by the Humphrey Field Analyzer Statpac program) were correlated in 137 patients. A moderate linear correlation (r = .66) was found. In 25 patients tested by both static and kinetic perimetry, the correlation could not be significantly improved by considering field loss outside of 30 degrees. The correlation was further studied in four subcategories of diagnosis: optic neuritis (n = 36), idiopathic intracranial hypertension (n = 26), compressive optic neuropathy (n = 14), and anterior ischemic optic neuropathy (n = 7). In compressive optic neuropathy and idiopathic intracranial hypertension, the difference in mean deviation between the two eyes was associated with a larger relative afferent pupillary defect than in optic neuritis and anterior ischemic optic neuropathy. In optic neuritis, the correlation was the poorest. These results indicate that diseases of the afferent visual system may not necessarily affect visual threshold (as tested by static perimetry) and the pupillary light reflex (a suprathreshold test) in the same way. PMID- 8442496 TI - The effect of reduced eyedrop size and eyelid closure on the therapeutic index of phenylephrine. AB - In this study we examined the relative effects of reducing eyedrop size (from 30 microliters to 10 microliters) and eyelid closure on the ocular efficacy and systemic absorption of 10% phenylephrine. Thirteen subjects participated in a quadruple crossover study that involved dilation with a 10-microliters and a 30 microliters drop of phenylephrine with and without eyelid closure. The 10 microliters drop was just as effective for pupillary dilation as the 30 microliters drop. Eyelid closure improved dilation for both drop sizes. Both eyelid closure and reducing the drug volume decreased systemic absorption of phenylephrine as measured by plasma concentration. When used together, eyelid closure and the smaller drop size reduced plasma concentration by 45%. The therapeutic index for 10% phenylephrine appears to be improved by using a 10 microliters drop followed by eyelid closure. PMID- 8442497 TI - Visual prognosis in autosomal dominant optic atrophy (Kjer type). AB - We examined 25 patients from three pedigrees with dominant optic atrophy (Kjer type). Follow-up on 20 patients ranged from five to 40 years (mean, 16 years; median, 13 years). Visual acuity ranged from 20/20 (in one 58-year-old man with an affected father and three affected children) to 20/400. The median initial visual acuity was 20/60, and the median final visual acuity was 20/80. Visual acuity remained unchanged or decreased by one Snellen line in both eyes of 13 patients (65%); it decreased between two and four Snellen lines in only one eye in three patients (15%) and in both eyes in four patients (20%). The rate of visual loss was unrelated to initial visual acuity or the particular pedigree to which the patient belonged. There was functional and ophthalmoscopic heterogeneity between and within the pedigrees. Eight patients perceived moderate to severe social or occupational handicap. Visual prognosis is relatively good in Kjer's dominant optic atrophy with stable or slow progression of visual loss. PMID- 8442498 TI - Chiasmal compression from fat packing after transsphenoidal resection of intrasellar tumor in two patients. AB - After transsphenoidal resection of a pituitary (or other) tumor, the remaining intrasellar cavity, and sphenoid sinus are usually packed with exogenous fat or muscle to prevent cerebrospinal leak and prolapse of the optic chiasm into an empty sella. We treated two patients in whom chiasmal compression occurred postoperatively because of packing of fat. In one patient, the expected visual improvement in the postoperative period was suboptimal. The subsequent removal of fat resulted in total visual recovery. In the other patient, chiasmal compression persisted from intrasellar fat and residual tumor. Iatrogenic compression of the optic nerves or chiasm should be considered in all patients in whom visual recovery is incomplete. PMID- 8442499 TI - Postoperative mydriasis after repair of orbital floor fracture. AB - Mydriasis after operative repair of orbital floor fracture has been attributed to manipulation of the inferior oblique muscle. We treated two patients with mydriasis, one with an isolated mydriatic pupil and the other with a tonic pupil, which followed posterior orbital floor injuries and repair. The posterior location of the fractures suggests that surgical manipulation of or near the ciliary ganglion may account for these phenomena. Patients should be warned before posterior orbital floor repair about possible mydriatic or tonic pupils as a complication. PMID- 8442500 TI - Deoxyribonucleic acid ploidy studies in choroidal melanomas. AB - In several tumors of different organ sites, the amount of DNA in a cell (ploidy) is associated with malignancy. We performed DNA quantitation in 21 choroidal melanomas and compared flow cytometry with image analysis in 11 of these melanomas. We modified our preparation technique to overcome problems with pigment and control cell populations in the image analysis group. Fifteen tumors were diploid and two tumors were tetraploid. Four tumors were unprocessable by flow cytometry, but two of these tumors were diploid by image analysis. Image analysis also detected tetraploidy in two tumors that were diploid by flow cytometry. During image analysis, cells were classified according to the Callendar classification and histograms were plotted for each cell type. All spindle A cells were diploid and most tetraploid peaks were formed by epithelioid cells. The use of image analysis on small samples of choroidal melanomas may be of value both in confirmation of diagnosis and prognosis of these lesions, and perhaps therapeutically, for example, in the monitoring of radiation treatment. PMID- 8442501 TI - Paraneoplastic retinopathy in malignant melanoma. PMID- 8442502 TI - Vitreous hemorrhage and extracorporeal membrane oxygenation. PMID- 8442503 TI - An unusual case of giant cell arteritis. PMID- 8442504 TI - Orbital metastasis from medullary carcinoma of the thyroid. PMID- 8442505 TI - Ocular findings in Larsen's syndrome. PMID- 8442506 TI - Visual loss after retrogasserian glycerol injection. PMID- 8442507 TI - Orbital cellulitis caused by Eikenella corrodens. PMID- 8442508 TI - Argon laser gonioplasty in the treatment of angle-closure glaucoma. PMID- 8442509 TI - Progression of nonproliferative diabetic retinopathy and visual outcome after extracapsular cataract extraction and intraocular lens implantation. PMID- 8442510 TI - Community care of corneal ulcers. PMID- 8442511 TI - Fast-responding, fibre-optic based sensing system for the volatile anaesthetic halothane, using an ultraviolet absorption technique and a fluorescent film. AB - An improved version of a fast-responding sensing system for the widely used volatile anaesthetic halothane (2-bromo-2-iodo-1,1,1-trifluoroethane) is described. The concentration of halothane is determined using an ultraviolet radiation (UV) absorption technique. Ultraviolet radiation at 230 nm is conveyed by a silica optical fibre to a gas flow-through cell containing the halothane, and the intensity of the UV reaching the other side of the cell is measured using a fluorescent polymer film. This paper describes the development of an efficient fluorescent polymer film for the sensor based on poly(ethylene glycol) containing two fluorophores (2,5-diphenyloxazole and tris[4,4,4-trifluoro-1-(2 thienyl)butane- 1,3-diono]europium(III)). The film fluoresces strongly with a red line spectrum when excited in the range from about 200 to 380 nm. There is evidence of direct energy transfer between the two fluorophores. A similar effect is observed in films prepared from Carbowax 20M and the europium chelate. An advantage of this approach is that the fluorescent radiation can be transmitted back to a silicon photo-detector using an inexpensive polymer optical fibre bundle. Two experimental sensor systems for halothane are described and the results show that, although the response does not obey the Beer-Lambert law, a reliable system for determining halothane can be constructed, which operates over the medically important range 0-3%. This paper also describes how the signal-to noise ratio of the system can be improved by using the long fluorescence lifetime of the film.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8442512 TI - Determination of malonaldehyde in human plasma: elimination of spectral interferences in the 2-thiobarbituric acid reaction. AB - A selective, derivative spectrophotometric method has been developed for the determination of malonaldehyde (MLD), based on a reaction with 2-thiobarbituric acid (TBA). The proposed method has been applied to the determination of MLD in human plasma. A study to eliminate several spectral interferences is described. A comparative study of the results obtained using the proposed derivative method and a conventional TBA method applied to human plasma is presented and the advantages of the proposed method over the conventional method for the determination of MLD in human plasma are evaluated. PMID- 8442513 TI - Development of a radioimmunoassay for the determination of buprenorphine in biological samples. AB - The development of a specific and sensitive radioimmunoassay for the detection of buprenorphine in urine samples is described. With minor adjustments, the assay was also applied to the analysis for buprenorphine in plasma samples. The 2 diazobenzoic acid derivative of buprenorphine has been prepared as a hapten. The immunization of rabbits with the hapten-bovine serum albumin conjugate resulted in the production of antibodies, which cross-reacted with N-dealkylbuprenorphine up to about the 90% level. The antibodies showed very low cross-reactivities with the 3-O-glucuronides and with the structural analogue etorphine. The assay was mainly used to pre-screen for buprenorphine in urine samples of persons suspected of Temgesic misuse and to determine buprenorphine in plasma samples. A linear calibration graph for buprenorphine was obtained after logit-log regression [Y = 0.383 (s, 0.059) - 0.535 X (s, 0.025); r = 0.997 (s, 0.001)]. The spiking recovery study showed a linear regression of Y (observed) = 0.94 + 0.84 X (expected); r = 0.997. Intra- and inter-assay relative standard deviations were < 4.35 and < 6.36%, respectively. A comparison study of the high-performance liquid chromatographic determination (X) to the radioimmunoassay (Y) resulted in the following regression equation for the urine samples: Y = 1.44 + 1.64 X (n = 32; r = 0.910) and Y = 0.007 + 1.58 X (n = 10; r = 0.930) for plasma specimens. The minimum detectable dose of the immunoassay was calculated to be 10 pg ml-1 (Student's t-distribution, p = 0.01, degrees of freedom = 8). PMID- 8442514 TI - Determination of patulin by reversed-phase high-performance liquid chromatography with extraction by diphasic dialysis. AB - A simple and economical method has been developed for the determination of patulin in apple juice. The sample is extracted with ethyl acetate in a diphasic dialysis system, and the extract is cleaned up by elution from a Sep-Pak cartridge. Patulin is detected and determined by reversed-phase high-performance liquid chromatography using a Novapak C18 column and an ultraviolet detector. The lower detection limit is 1 microgram l-1 and the recovery is 85% at the 20 micrograms l-1 level. PMID- 8442515 TI - Spectrofluorimetric method for the quantification of 7-hydroxycoumarin in urine and plasma using both extracted and unextracted samples. AB - A sensitive spectrofluorimetric assay has been developed for the determination of 7-hydroxycoumarin (7-OHC) in urine and plasma. Assay systems for urine and plasma were developed and compared with regard to linearity, accuracy, precision, limit of quantification, percentage recovery and assay time. The amount of 7-OHC conjugated to glucuronide and excreted in the urine, was determined following treatment with beta-glucuronidase (5000 U ml(-1);1 U = 16.67 nkat) for 30 min at 37 degrees C. This allows the urinary concentration of free, total and conjugated 7-OHC to be determined. Samples were extracted with diethyl ether and a suitable aliquot of reconstituted extract diluted in 0.1 mol 1(-1) phosphate buffered saline (PBS), pH 10.0 and transferred to a 96 well microtitre plate. The 7-OHC concentration was also determined without prior solvent extraction. Aliquots (20 microl) of urine and plasma samples were transferred to a 96 well microtitre plate and dilutes to 200 microl with PBS, pH 10.0. The fluorescence intensity was determined at excitation and remission wavelengths of 370 and 450 nm, respectively, for both extracted and unextracted samples. Linear ranges of 7-OHC in urine and plasma, using either method, were found to be 0.5-10 and 10-100 micrograms ml(-1). Inter- and intra-day precision studies, using both methods, demonstrated relative standard deviations of below 10% across the linear range. The limit of quantification of 7-OHC in urine and plasma was 0.5 micrograms ml( 1) using both methods. Both methods have been used successfully to determine the concentration of 7-OHC excreted in the urine of patients. The percentage of the dose recovered as 7-OHC over a 24 h period was 92-98%, using unextracted and extracted samples, respectively, with 98% of this recovered as the glucuronide conjugate. The two methods are a significant improvement on a previously described method and provide an alternative to high-performance liquid chromatography. PMID- 8442516 TI - Tuberculosis contact investigation: two years of experience in New York City correctional facilities. AB - BACKGROUND: An increasing incidence of tuberculosis has been observed in the New York City correctional system. METHODS: The diagnosis of active tuberculosis in persons within the correctional setting results in an investigation, with the identification and screening of contacts. RESULTS: Thirty-four such investigations in the past 2 years in the New York City correctional system, where all inmates are screened for tuberculosis on admission, have resulted in an overall tuberculin skin test conversion rate of 6.74% in 1306 inmates. In 21 of these investigations the index had both smears and cultures positive for Mycobacterium tuberculosis and the conversion rate was 7.37% in 719 contacts tested. In seven investigations the index patient had a culture only positive for M. tuberculosis and the conversion rate was 6.58% in 243 inmates. In six investigations in which the index patients were subsequently found to have nontuberculous pneumonia or mycobacteria other than M. tuberculosis the conversion rate was 5.52% in 344 inmates. These rates are not statistically different. CONCLUSIONS: Whether the observed conversions in these events or in any of the contact investigations are due to intramural spread, anergy on admission, the booster phenomenon, or incubation of disease on admission is not known. The 5.5% conversion rate in those exposed to inmates confirmed not to have tuberculosis suggests the influence of booster phenomenon and consideration of two-step testing on admission. PMID- 8442517 TI - A cluster of coagulase-negative staphylococcal bacteremias associated with peripheral vascular catheter colonization in a neonatal intensive care unit. AB - BACKGROUND: A cluster of six neonatal cases of coagulase-negative staphylococcal bacteremias occurred in a Los Angeles County neonatal intensive care unit in March 1989. METHODS: A retrospective cohort study assessed the impact of host-and delivery-related variables, length of hospitalization, duration of antibiotic treatment, performance or duration of invasive procedures, and staffing variables on risk of coagulase-negative staphylococcal bacteremia. RESULTS: Unstratified analyses yielded eight risk factors with risk ratios greater than 2. After stratification by gestational age (less than 29 weeks) and low birth weight (less than 1500 gm), frequency of blood transfusions, duration of respiratory therapy, heparin lock and central vascular line placement, and hyperalimentation remained associated with elevated risk. Two species were identified, arguing against a common source of infection. Of four cohort months with more than 15 very low birth weight infants in the neonatal intensive care unit, an elevation of coagulase-negative staphylococcus-positive blood cultures and diagnosed bacteremias occurred in only two. CONCLUSIONS: This cluster of coagulase-negative staphylococcal bacteremia was probably caused by frequent manipulation of catheters in neonates who were at heightened risk because of low birth weight and prematurity. PMID- 8442518 TI - Nosocomial legionellosis: a review of pulmonary and extrapulmonary syndromes. AB - Surgical patients appear to be at highest risk for acquisition of nosocomial Legionella pneumonia; most appear to become infected during respiratory tract manipulation and mechanical ventilation. Although the lungs are the most common site of nosocomial Legionella infection, an important subset of patients have infection at extrapulmonary sites. We describe 22 cases of extrapulmonary legionellosis reported in the literature. Most of these patients were surgical patients; more than half did not have serious underlying illnesses, and only five (23%) were receiving immunosuppressive agents. A total of 13 extrapulmonary sites of infection were reported, many in the absence of clinical pneumonia; these infections included sinusitis, hip wound infection, and prosthetic valve endocarditis. Five patients (23%) had fatal infections; in four of these cases diagnosis of Legionella infection was made after death, underscoring the need for a high index of clinical suspicion. A large percentage of extrapulmonary Legionella infections may result from direct topical exposure of susceptible tissue to contaminated tap water. Use of tap water must be carefully monitored, particularly in dressing changes and bathing of surgical patients. PMID- 8442519 TI - Effects of steam sterilization on the contents of sharps containers. AB - BACKGROUND: One form of medical waste known to be capable of transmitting disease is the contaminated sharp. Safe handling and disposal of sharps is an essential element of any infection control program. Many areas allow the on-site treatment of sharps containers. However, little information currently exists as to the most effective sterilization procedures and container designs. METHODS: This study was intended to evaluate the effect treatment with various autoclaves had on bacterial endospores present on strips or needled syringes. Strips contained 1.7 x 10(5) Bacillus stearothermophilus spores; syringes were soiled with equal numbers of spores or with spores plus blood. Syringes were tested capped and uncapped. A gravity-displacement autoclave and a high-vacuum autoclave were used. Strips and syringes were placed within sharps containers three quarters filled with representative materials. Six types of containers were tested. Containers were processed sitting up or on their sides. Processed strips and needles were aerobically cultured at 56 degrees C for 7 days. If sterilization was not accomplished initially, additional exposure time was added. RESULTS: (1) Soiled syringes were more difficult to sterilize than strips. (2) Capping or the presence of blood did not affect sterilization efficiency. (3) Container positioning was important only for the gravity-displacement autoclave. (4) Additional exposure time was required in the gravity displacement autoclave when sterilizing soiled syringes but not strips. (5) High-vacuum autoclaving killed all spore challenges within the normal processing interval. CONCLUSIONS: The data indicate that processing of sharps containers within a gravity-displacement autoclave appears to require extended exposure intervals to achieve sterilization. PMID- 8442520 TI - Microbial contamination of enteral feeding solution and its prevention. AB - In an investigation of microbial contamination of enteral feeding solutions, all 22 residual solutions obtained immediately after administration were contaminated at concentrations of 10(3) to 10(6) viable counts/ml. Major contaminants were glucose-nonfermenting gram-negative bacilli such as Pseudomonas aeruginosa and Acinetobacter calcoaceticus var anitratus. Contamination seemed to have been caused by frequent reuse of bag-type containers and the infusion tubes connected to the bags, neither of which can be washed or dried. Decontamination methods were evaluated by using polypropylene containers that can be washed and disinfected for administration. Few Serratia marcescens on the inside wall of the container were removed by rinsing with tap water, alone or in combination with detergent scrub. Tap water and detergent plus air-drying at 56 degrees C for 1 hour reduced Serratia marcescens only somewhat. Tap water and detergent plus immersion in 0.01% sodium hypochlorite for 1 hour or in water at 70 degrees C for 3 minutes eliminated all 10(11) cells of Serratia marcescens. PMID- 8442521 TI - Evaluation and implementation of a needleless intravenous system: making needlesticks a needless problem. AB - A needleless intravenous (IV) system with blunt plastic cannulas and specially designed injection sites was introduced at Olive View Medical Center to reduce needlestick injuries, particularly IV-related needlesticks. IV-related needlestick injuries decreased 72% during the first 8 months of use, costs were reduced $1.85 for a typical IV piggyback administration set-up by revising the IV piggyback procedure, and a staff survey revealed satisfaction with the new system. PMID- 8442522 TI - False-positive results of spore tests from improper clip use with the STERIS chemical sterilant system. PMID- 8442523 TI - Meaningful interhospital comparisons of infection rates in intensive care units. PMID- 8442524 TI - Hepatitis C in the health care setting. II. Seroprevalence among hemodialysis staff and patients in suburban New York City. AB - BACKGROUND: Hepatitis C virus (HCV) is a newly identified blood-borne virus that may pose an occupational hazard for health care workers. Hemodialysis nurses could be anticipated to be at high risk for HCV infection because this group of health care workers frequently comes into contact with blood of a patient population with a seroprevalence rate of at least 10%. METHODS: To assess the risk of HCV infection for hemodialysis nurses, serum samples from all of the nurses (22/22, 100%) and patients (125/125, 100%) in one hemodialysis unit (unit A) and 85% (29/34) of nurses from a second unit (unit B), both units in suburban New York City, were tested for HCV antibodies. Samples with positive results of enzyme-linked immunosorbent assay underwent supplemental testing by a first generation recombinant immunoblot assay. RESULTS: Twenty-four (19%) of the hemodialysis patients in unit A were HCV seropositive. Despite an average of 4.7 years spent working in hemodialysis unit A, none of the nurses tested seropositive for HCV antibody. In unit B, despite an average of 6.4 years working in the unit studied, only one nurse tested seropositive for HCV antibody. This nurse reported a long history of elevated liver function values and a negative HBV core antibody status that predated her hemodialysis nursing career. CONCLUSIONS: In contrast to the experience with hepatitis B virus infection, hemodialysis nurses appear to be at low risk for occupationally acquired HCV infection. PMID- 8442525 TI - Rapid assessment of human immunodeficiency virus seroprevalence in a community based hospital. AB - BACKGROUND: To aid in development of patient testing policy, in-service education, and resource planning, it is necessary to have a useful and meaningful tool for determining the population-specific HIV seroprevalence rate for our hospital patients. We were offered by the Centers for Disease Control a newly developed survey tool: "Rapid Assessment of HIV Seroprevalence in Hospital Patients." We subsequently served as one pilot site for this tool. METHODS: A population-based sample of 1000 patients (500 inpatients, 500 outpatients) was stratified into age and sex groups on the basis of admission statistics from the previous year in a general community hospital system in southeastern Pennsylvania that consists of two clinical campuses: an urban site with 343 beds and a suburban site with 506 beds. The study was conducted as an anonymous, unlinked screening for HIV antibody in 1000 serum samples. RESULTS: We found our overall seroprevalence rate to be 2.60% (Poisson 95% confidence interval, 1.77% to 3.81%), or 1 in 38 patient specimens. The highest rates for both sexes were found in the age range 25 to 44 years. CONCLUSIONS: This protocol is a useful survey tool for community hospitals to determine the HIV seroprevalence rate in patient populations, a practical necessity for planning and education. Survey results would aid in implementation of current Centers for Disease Control guidelines for HIV testing of inpatients and outpatients in the acute care hospital setting. PMID- 8442526 TI - Comparison of duplex ultrasonography and ascending contrast venography in the diagnosis of venous thrombosis. AB - The application of duplex ultrasonography to the diagnosis of venous thrombosis requires validation by comparison of the duplex findings with the results of ascending contrast venography. In this study, 2534 veins were examined by both methods with contrast venography results serving as the standard for comparison. In this setting, duplex ultrasonography proved to be 100% sensitive and 99% specific for venous thrombosis. Duplex ultrasonography is as reliable as venography in the diagnosis of venous thrombosis and has no associated risks or known complication. In addition, duplex ultrasonography provides information regarding pathologic anatomy that is comparable to the detail provided by high quality venography. The authors conclude that duplex ultrasonography should be the diagnostic method of choice for evaluating patients with suspected venous thrombosis. PMID- 8442527 TI - Experimental manufacture of a catheter for the measurement of blood flow rate. AB - The authors manufactured an experimental catheter to obtain blood flow rate, measuring not only the flow velocity but also the vessel diameter. This catheter consists of 3F Doppler and 7F external sheath catheters, and four thin wires 3 cm in length are attached to the catheters at both tips at a 90 degrees pitch. After the insertion of the catheter into the vessel, vessel diameter is calculated from the maximal width of the wires, which are expanded to a spindle shape inside the vessel; the maximal width is corrected with calibration metal markers also attached at the proximal site of the external sheath catheter. The flow velocity of the blood is calculated with the FFT (Fast Fourier Transform) analyzer. In experimental circuits as well as in the canine aorta, wires were adequately expanded, and the catheter was placed at the center of the tube or the aorta. The blood flow rate, which was calculated as a product of flow velocity and vessel diameter, was well correlated to that from the electromagnetic flowmeter, not only in the experimental circuits, but also in the canine aorta. PMID- 8442528 TI - Value of finger arterial blood pressure in diagnosis of vascular changes in some connective tissue diseases. AB - This study was performed in 60 patients with the following connective tissue diseases: rheumatoid arthritis (RA--20 patients), systemic lupus erythematosus (SLE--20), and progressive systemic sclerosis (scleroderma = PSS--20). Twenty normal persons served as controls. All patients and controls were subjected to complete history taking, complete physical examination, and laboratory investigations including: rheumatoid factor, anti-DNA, LE cell test, antinuclear factor (ANF), and ECG. Finger arterial blood pressure (FABP) readings using an 8 MHz Doppler flow detector with a 24-mm-diameter cuff at a temperature of 24 degrees C were made in all cases and controls. The mean age of incidence in patients with RA was 37.8 years; in those with SLE, 21.5 years; in those with PSS 34.6 years; and in the control group, 33.7 years. Women were predominant both in the diseases and the control groups. The FABP was measured in all groups and the range of difference between the brachial and finger arterial blood pressure in each group was estimated. In the control group the mean difference was 27.7 mm Hg; in the RA group, 45.8 mm Hg; in the SLE group, 58.1 mm Hg; and in the PSS group, 70.9 mm Hg. There were no significant peripheral vascular changes in the small arteries in the RA group, whereas in the SLE and PSS groups there was a significant difference, which suggests different underlying microvascular changes. The FABP appears to be a diagnostic tool in the diagnosis of PSS and it helps in differentiation between various types of collagen disease in equivocal cases. PMID- 8442529 TI - Raynaud's syndrome, an enigma after 130 years. AB - The recent literature concerning Raynaud's syndrome is reviewed. Raynaud's syndrome is as common as hypertension and diabetes. In spite of its generally benign character, it causes a lot of discomfort to individuals and sickness absenteeism to society, especially in the colder regions of the world. The etiology remains an enigma 130 years after its first description, perhaps even more so than ever before, the many new theories proposed in the literature. Clearly, in a condition where seventy different etiologic theories are advocated, the culprit lesion is obviously missing, or there is not a culprit lesion but an accumulation of conditions having nothing in common but a few symptoms. Moreover a Raynaud attack may result, not from a single event, but from a cascade of events, just as, for example, hemostasis does. Controversy about diagnosis exists all over. For example, how does one make a diagnosis? Patient history has been considered unreliable. A standardized cold test, though highly reproducible in the authors' hands, is far from common property. Raynaud's syndrome is a condition for which thirty-eight therapies have been advocated in the last three years, but the curative answer is still to come. PMID- 8442530 TI - Radiological aspects of arteriosclerosis: follow-up study of 588 patients in two different groups. AB - The authors retrospectively compared two groups of patients who had undergone angiography over a twenty-one-year period. The first group consisted of 348 patients who had angiography in the years 1965-1967. The second group was made up of 222 patients who had had angioplasty in the years 1975-1986. Special risk factors such as diabetes and nicotine abuse were singled out together with localization of lesions and gender distribution. PMID- 8442531 TI - Atrial septal defect after balloon mitral valvuloplasty: a transesophageal echocardiographic study. AB - Fifty patients with rheumatic mitral stenosis aged twelve to thirty-six (twenty +/- six) years were studied by two-dimensional, pulsed and color Doppler echocardiography during, seventy-two hours after, and biweekly for three months after balloon mitral valvuloplasty (BMV). Transesophageal echocardiography (TEE) done immediately after BMV (in the catheterization laboratory) detected a new atrial septal defect (ASD) in 46 (92%) patients. These measured 1 to 2 (mean 1.2 +/- 0.3) mm in diameter. Doppler color flow mapping guided the location of the ASD in most of the cases. A narrow jet of left-to-right shunt could be evaluated by pulsed Doppler studies. Velocity time integral (VTI) of the jet across one cardiac cycle and the diameter of the ASD were used to calculate the left-to right shunt (shunt = VTI x pi (D/2)2 x heart rate). The estimated shunt was 0.04 0.39 (mean 0.20 +/- 0.10) L/minute. A repeat study at seventy-two hours revealed the defect in 40 (80%) patients. At three months, the defect persisted in only 5 (10%) cases. The mean interval of closure of ASD was 4.6 +/- 2.2 weeks. The authors conclude: (1) ASD occurs commonly after BMV, (2) the septal defect and the resultant left-to-right shunt are insignificant, and (3) ASD disappears in the majority of cases by three months after BMV. PMID- 8442532 TI - Treatment of arteriosclerotic obstruction by LDL adsorption. AB - According to the authors' clinical analysis, about half of the patients who suffer from arteriosclerotic obstruction (ASO) in the lower extremity(-ies) with clinical manifestation are dyslipidemic (total cholesterol > or = 220 mg/dL or LDL cholesterol > or = 140 mg/dL). As suggested by clinical success in regression of ASO in the coronary arteries as a result of aggressive removal of LDL, LDL adsorption utilizing an extracorporeal circulation technique with a dextran sulfate/cellulose adsorbent column was applied in 33 patients (22 men and 11 women) with ASO. Clinical results obtained after a series of 10 LDL adsorption procedures as a standard showed encouraging success. Improvement in subjective symptoms was achieved as follows: 88.5% for cold lower extremity, 87.1% for intermittent claudication, 53.8% for leg/toe pain at rest, and 60% for disappearance/size diminution of ulcer/necrosis. Improvements in objective examination findings supported subjective ones: 85.7% by plethysmography, 81% by thermography and 70% by ankle pressure index. No serious complications or untoward effects were observed during or after the adsorption procedures. In conclusion, LDL adsorption appears to be a useful and safe tool in treatment of ASO patients with dyslipidemia. PMID- 8442533 TI - Vasodilative response to hypoxia and simulated ischemia is mediated by ATP sensitive K+ channels in guinea pig thoracic aorta. AB - Local vasodilation in response to hypoxia or ischemia improves perfusion and O2 supply of the affected tissue. This local vasodilation thus constitutes the most important mechanism in the prevention of ischemic cell injury. The regulation of vascular tone has mainly been attributed to changes of cytoplasmatic Ca2+ ((Ca2+)i) concentrations in vascular smooth muscle cells. The mechanism underlying these changes has not, however, been elucidated so far. Using aortic strips of guinea pigs (transversally cut in spirals; normal Tyrode, in mM: NaCl 150, KCl 4.5, MgCl2 2, CaCl2 2.5, glucose 10; buffered with 10 mM HEPES at pH 7.4; equilibrated with 100% O2 at 31 degrees C) the authors could show that metabolic blockade (glucose replaced by 10 mM 2-deoxyglucose (DOG) led to a relaxation of the preparation. Thus, in four experiments, resting tension decreased from 0.75 g by 27% +/- 12% within two hours (% of maximal contractile force developed by each preparation when depolarized with 43 mM KCl and 101.5 mM NaCl). When the same experiment was carried out in the presence of 1 mM tolbutamide (a known blocker of ATP-dependent K+ channels) in vascular smooth muscle no such relaxation could be seen (n = 4). Furthermore, in the same type of preparation, similar results have been obtained upon hypoxic relaxation (100% O2 replaced by 100% N2), where 1 mM tolbutamide also prevented vasodilation. Thus, hypoxic/ischemic vasodilation in response to glycolytic inhibition (DOG) and hypoxia (N2) is based upon the opening of K+ ATP channels and hence can be prevented by sulfonylureas (the opening of K+ ATP channels would lead to hyperpolarization (increased K+ conductance, Goldmann equation), thus diminishing the open probability of voltage-gated Ca2+ channels with subsequent vasodilation). This inhibition by sulfonylureas of vasodilative response to ischemia may also constitute the so far unknown cause of the increased cardiovascular mortality seen under sulfonylurea treatment. PMID- 8442534 TI - Erythromelalgia unmasked during norephedrine therapy: a case report. AB - A thirty-eight-year-old woman presented with typical signs of erythromelalgia: burning, redness, and warm congestion of the extremities. These symptoms occurred after cessation of obesity drug therapy with norephedrine (250 mg/day) continuously over six years. The condition was refractory to treatment with acetylsalicylic acid. It is suggested that erythromelalgia in this case was unmasked by the vasoactive properties of norephedrine. Continuous drug therapy with norephedrine may have led to adaptive adrenergic subsensitivity of vascular smooth muscles. The pathomechanism of primary erythromelalgia is still unknown. Their observations suggest that an enhanced vasodilatation due to an abnormal adrenergic sensitivity may play an important role in the pathogenesis of primary erythromelalgia. PMID- 8442535 TI - Traumatic rupture of the aorta with ductus diverticulum: a case history. AB - Traumatic rupture of the aorta is a life-threatening injury with an extremely high mortality rate if not promptly diagnosed and surgically repaired. Accurate diagnosis depends on a high index of suspicion and the correct assessment of the angiographic features revealed by aortography. A case is presented that illustrates the angiographic findings in a patient with traumatic rupture of the aorta with an accompanying ductus diverticulum. A ductus diverticulum, which is located just distal to the aortic isthmus, can be confused with an aortic tear angiographically and vice versa. The case discussed demonstrates the difference between these two entities. PMID- 8442536 TI - Massive spinal cord infarction with multiple paradoxical embolism: a case report. AB - A sixty-seven-year-old man suffered from acute anterior spinal artery syndrome at the level of T-10. Transverse myelopathy developed by the eighth day. Computed tomography of the brain on the thirteenth day demonstrated hemorrhagic infarction in the left occipital lobe and fresh ischemic infarction in the right cerebellar hemisphere. Respiratory distress was the cause of death on the fifteenth day. Autopsy study showed severe ischemic necrosis of the spinal cord below T-10, and multiple infarcted lesions in the brain, lung, kidney, and heart. Saddle thromboembolism of the bilateral trunk of the pulmonary artery was the major cause of his death. Deep venous thrombosis in the pelvis was disclosed to be the primary source of multiple paradoxical embolisms through the patent foramen ovale. PMID- 8442537 TI - Analysis of childhood pedestrian deaths in New Mexico, 1986-1990. AB - STUDY OBJECTIVE: To determine if the mechanism of fatal childhood pedestrian injuries correlated with location, injury pattern, and age of the pedestrian and to determine ethnic differences in fatality rates. DESIGN: Retrospective review of state medical investigator reports and autopsies from 1986 to 1990. Logistic regression and chi 2 were used to test for statistically significant differences between the groups in our data set. TYPE OF PARTICIPANTS: New Mexican children, 0 to 14 years old fatally injured by moving vehicles. RESULTS: Sixty-four children died for an overall fatality rate of 3.8 (per 100,000). Native American children and children younger than 5 years experienced the highest fatality rates. Children younger than 5 years were more likely to be crushed under the wheels of a slow-moving vehicle in both a nontraffic and a traffic location, whereas older children were found more often to have died from injuries from a high-speed impact event in a traffic location (P < .001). Leg fractures (P = .001) and spinal fractures (P = .02) occurred more frequently in impact than crush injuries. CONCLUSION: Young children are at risk for a crush injury in both the traffic and nontraffic environment. PMID- 8442538 TI - Fire fatalities among New Mexico children. AB - STUDY OBJECTIVE: To explore the relationship between social conditions and fire mortality rates among children. DESIGN: Retrospective analysis of fire fatalities in children 0 to 14 years old in New Mexico. SETTING: State Office of the Medical Investigator. TYPE OF PARTICIPANTS: All 57 New Mexico children 0 to 14 years old who died from fire-related injuries from 1981 through 1991. INTERVENTIONS: Medical investigator and autopsy records were reviewed and abstracted. Demographic and housing figures were obtained from US Census reports. Data were analyzed by chi 2 or by Fisher's exact test, with Bonferroni correction for multiple comparisons. RESULTS: Two thirds of decedents were male (P = .0014), and three fourths were less than 5 years old (P < .0001). Children living in mobile homes had triple the mortality rate of those in houses or apartments, and children in homes without plumbing (substandard) had more than ten times the mortality rate of those in houses or apartments (P < .0001). Two thirds of the victims in substandard homes were Native American (P < .0001). Errors or negligence of adults occurred in more than half of the deaths. Eighty-two percent of decedents died at the scene; only 11% reached a burn center. CONCLUSION: Substandard homes are associated with an increased fire mortality rate among children. Strategies to prevent childhood fire fatalities should address housing conditions and adult safety practices. Enhanced prehospital or burn unit care is unlikely to greatly affect childhood fire mortality rates. PMID- 8442539 TI - Effect of environmental conditions on emergency department use by wheezing children. AB - STUDY OBJECTIVE: To examine in children the relationship of wheezing to measurable environmental factors. STUDY DESIGN: Multiple regression analysis was used to measure correlation with air quality, weather, and seasonal and infection related variables. RESULTS: Daily wheezing census was significantly correlated with weather and seasonal variables and the daily infection census. We are not certain which weather variable is the dominant factor in the weather association because all of the weather variables have some degree of colinearity. Air quality as measured by carbon monoxide and airborne particles was not shown to be associated with wheezing. CONCLUSION: A high incidence of pediatric emergency department presentations for wheezing are associated with weather, infections, and months of the year. PMID- 8442540 TI - Endotracheal tube selection in children: a comparison of four methods. AB - STUDY OBJECTIVE: To determine the accuracy of four methods of endotracheal tube size selection in the pediatric population. STUDY DESIGN: Prospective, blinded comparison. SETTING: The Children's Hospital of Philadelphia. PARTICIPANTS: Two hundred thirty-seven children aged 1 month to 9 years old undergoing elective surgery requiring endotracheal intubation. SELECTION PROCEDURES: Consecutive sample. INTERVENTIONS: Four methods of determining proper endotracheal tube size in children were compared. These methods included direct comparison with the width of the fifth finger, direct comparison with the diameter of the fifth finger using a ring-sizing device, direct comparison with the width of the fifth fingernail, and estimation using a formula ([age in years + 16]/4). In infants, a 3.0-mm (internal diameter) endotracheal tube was predicted for those 3 months of age and younger, and a 3.5-mm endotracheal tube was predicted for those from 3 to 9 months of age. The size of the endotracheal tube used in the operating room was recorded, as was the "air leak" around the tube. An appropriately sized endotracheal tube was determined by an air leak with ventilation pressures between 5 and 40 cm of water. MAIN RESULTS: Direct comparison using the width and the diameter of the fifth finger predicted an endotracheal tube between 1 mm smaller and 0.5 mm larger than that used by the anesthesiologists in 11% and 14% of patients, respectively. The age-based formula predicted an endotracheal tube size in this range in 97.5% of patients, and direct comparison with the width of the fifth fingernail predicted an endotracheal tube in this same range in 91% of patients. These findings were consistent within all age groups studied. CONCLUSION: Neither fifth finger width nor fifth finger diameter accurately predicts proper endotracheal tube size in most children. A more accurate estimation can be made using the age-based formula, but when the child's age is unknown or when calculation is awkward or impossible, an accurate estimate can be made using the width of the fifth fingernail. PMID- 8442541 TI - Epidural hematomas in children. AB - STUDY OBJECTIVE: To describe the presentation, management, and outcome of children with traumatic epidural hematoma. DESIGN: Retrospective chart review. TYPE OF PARTICIPANTS: Fifty-three children diagnosed with traumatic epidural hematoma on computed tomography scan who were treated at Children's Hospital in Boston between 1980 and 1990. MAIN RESULTS: Twenty-four of 53 children developed an epidural hematoma after a fall of less than 5 ft. At the time of diagnosis, 51 of 53 children had one or more symptoms of vomiting, headache, or lethargy. Twenty-six patients were alert, 21 were responsive to verbal or painful stimuli, and five were unresponsive or posturing. Twenty-one (40%) had acute neurologic deterioration before surgery; however, 20 (38%) were alert with normal vital signs and neurologic examinations at diagnosis. All patients survived, and at the time of discharge 45 had normal examinations and eight had neurologic abnormalities; at follow-up only four of these eight had persistent (although mild) abnormalities. CONCLUSIONS: Although often dramatic in presentation, epidural hematoma may occur after relatively minor head trauma and in alert children with nonfocal neurologic examinations. In our study, incidence of neurologic sequelae increased if abnormal neurologic examination or depressed mental status was present at diagnosis. The outcome of children in this study is improved from that of previous studies, perhaps due to increased use of computed tomography and higher incidence of low- or moderate-impact trauma in this series. PMID- 8442542 TI - Proposed fellowship training program in pediatric emergency medicine for emergency medicine graduates. AB - Interest in pediatric emergency medicine has grown steadily during the past decade among pediatricians and emergency physicians. With the rapid proliferation of pediatric emergency medicine programs for pediatricians has come extensive and valuable experience with this type of fellowship education. As a result, the structure and scope of these programs have become increasingly well established. Because the number of pediatric emergency medicine fellowship programs for emergency physicians has yet to reach "critical mass," no similar de facto standards exist for these programs. The recent establishment of guidelines for pediatric emergency medicine subspecialty certification by the American Board of Emergency Medicine and the American Board of Pediatrics brings new importance to fostering such standards for the training for emergency physicians. To this end, we present a proposed pediatric emergency medicine fellowship program developed during a retreat that included physicians from an emergency medicine program and two pediatric hospitals. We also review some of the significant events that have occurred in the evolution of pediatric emergency care. PMID- 8442543 TI - Pediatric injury prevention annotated bibliography. PMID- 8442544 TI - Massachusetts emergency medicine closed malpractice claims: 1988-1990. AB - STUDY PURPOSE: To describe the characteristics of malpractice claims against emergency physicians and to identify causes and potential preventability of such claims. POPULATION: Malpractice claims closed in 1988, 1989, and 1990 against emergency physicians insured by the Massachusetts Joint Underwriters Association were compared with claims closed from 1980 to 1987 as investigated in our previous study. METHODS: Retrospective review of malpractice claim files by board certified emergency physicians. RESULTS: The average indemnity and expense per claim were higher in the current study population than in our previous study population (P = .05). Claims in eight high-risk diagnostic areas (chest pain, abdominal pain, fractures, wounds, pediatric fever/meningitis, subarachnoid hemorrhage, aortic aneurysm, and epiglottitis) accounted for 50.8% of claims in this study and 55.5% of total monetary losses. Four claims in this study were related to two instances of failure of an emergency department radiograph follow up system. The evaluation of patients who were intoxicated contributed to major monetary losses, especially in cases of fractures and head injury. CONCLUSION: Emergency physicians must have a particular awareness of their great risk exposure for missed myocardial infarction. Addition of dictation or voice activated record generation systems, departmental protocols for radiograph follow ups, and holding and re-evaluation of the intoxicated patient will help provide systems supports for reducing the liability of individual emergency physicians. PMID- 8442545 TI - Follow-up compliance after emergency department evaluation. AB - STUDY OBJECTIVE: To identify factors associated with outpatient follow-up of emergency department visits. DESIGN: A retrospective review of 587 ED charts meeting strict criteria was performed. The following variables were identified: method used to arrange follow-up, age, sex, consultant contacts, distance from patient's residence to hospital, previous physician, recommended time to clinic return, and funding source. Compliance was assessed using the outpatient registration computer data base. SETTING: ED and outpatient clinics of an urban university teaching hospital. PARTICIPANTS: Inclusion criteria were age between 18 and 75 years, patient released to outpatient care, and instructions specifying a university hospital clinic or ED follow-up and a time period within which this appointment was to occur. Follow-up options included patients being asked to return to the ED on a specific day (group 1), being given a specific clinic appointment (group 2), or being given the clinic telephone number and instructed to call for an appointment (group 3). RESULTS: Compliance rates, defined as follow-up within seven days of the recommended date, were group 1, 51%; group 2, 65%; and group 3, 46%. Significant confounding factors adversely affecting follow up as determined by multiple logistic regression analysis were decreasing age (P < .05), absence of insurance (P < .01), and no ED consultation with follow-up clinic physician (P < .01). Controlling for these factors and the reason for follow-up showed that having the patient schedule their own follow-up was associated with poor follow-up compliance (P < .001). CONCLUSION: Compliance with follow-up is multifactorial. Consultant contact at the time of initial patient evaluation and provision of a return visit appointment at the time of ED release should improve compliance in a university hospital setting. PMID- 8442546 TI - Effect of emergency department information on patient satisfaction. AB - STUDY HYPOTHESIS: Patient satisfaction with emergency department care is enhanced by information distributed to patients on ED arrival. PARTICIPANTS AND SETTING: A convenience sample of 200 alert, English-speaking, adult ED patients. DESIGN AND INTERVENTION: ED information was distributed on alternate days to all ED patients. The ED information described ED function and patient evaluation time. Patients not receiving ED information served as controls. A research assistant administered a satisfaction questionnaire to all patients immediately after discharge. MEASUREMENTS AND MAIN RESULTS: Patients who received ED information rated their overall satisfaction higher than did the control group (P < .0001). Other items rated significantly higher were physician skill and competence (P = .0112), physician concern and caring (P = .0062), whether the patient would use the same ED again (P < .0001), appropriateness of ED time (P = .01), information received (P < .0001), ability of staff to decrease anxiety (P < .0001), physician's explanation of illness and treatment (P = .0366), and ease and convenience of care (P = .0014). CONCLUSION: ED information has a significant effect on patients' perceptions of the quality of care and overall satisfaction. PMID- 8442547 TI - Functional illiteracy among emergency department patients: a preliminary study. AB - STUDY OBJECTIVES: To determine the ability of emergency department patients to understand common written discharge instructions and the level of reading difficulty of standard discharge instructions. DESIGN: The study was performed in two parts. In part 1, subjects were asked to read one set of standard written discharge instructions. Then, with the instructions to refer to, subjects were asked to answer five questions about the instructions. A subject's level of success was correlated with age, sex, and highest level of education. In part 2, 47 sets of standard written discharge instructions from six different EDs were computer analyzed using five commonly used readability formulas. Results were reported as grade levels. SETTING: The ED of a large inner-city university hospital. TYPE OF PARTICIPANTS: The subjects for part 1 were 400 adult ED patients who presented on randomly selected days. MEASUREMENTS AND MAIN RESULTS: Part 1: A significant proportion of patients failed to answer correctly at least four of five questions. Patients educated beyond high school demonstrated higher levels of success than did those with less education. A trend was noted for younger subjects to perform better than older subjects. The answers to the three most frequently missed questions were contained within areas of difficult sentence structure or long paragraphs containing large amounts of information. Part 2: The average grade level required to understand instruction sheets ranged from 6.0 to 13.4. More difficult instruction sheets tended to contain numerous multi-syllabic words, long sentences, and difficult sentence structure. CONCLUSION: A significant proportion of ED patients have a demonstrable inability to understand common written instructions. ED instruction sheets are written at a level of difficulty that is out of the readable range for many patients. Health care providers should strive to simplify written materials and to develop new methods for instructing those for whom current written materials have no meaning. PMID- 8442548 TI - Missed diagnoses of acute myocardial infarction in the emergency department: results from a multicenter study. AB - STUDY OBJECTIVE: To determine the rate of missed acute myocardial infarction (AMI) in the emergency department and the factors related to missed diagnoses. STUDY DESIGN: Observational and case-control study. SETTING: Data were analyzed from a multicenter study of coronary care unit admitting practices that included patients who presented to the ED with chest pain or other symptoms suggestive of acute cardiac ischemia (N = 5,773). Patients with missed AMI (cases) were compared with control patients admitted with AMI and to a second control group of patients discharged without AMI. RESULTS: Of 1,050 patients with AMI, 20 (1.9%; 95% confidence interval, 1.2-2.9%) were not admitted. Patients with missed AMI were significantly less likely to have ECG changes and a history of AMI or nitroglycerin use than patients admitted with AMI. However, they were significantly more likely to have ECG changes than patients discharged without AMI. Five patients with missed AMI (25%) had ST-segment elevation, and seven (35%) were discharged with a diagnosis of ischemic heart disease by the physician in the ED. Death or potentially lethal complications occurred in 25% of missed AMI patients. CONCLUSION: The rate of missed AMI in the ED was only 1.9%. However, 25% of these might have been prevented had ST-elevation not been missed, and another 25% might have been prevented had patients who were recognized to have ischemic heart disease by the physician in the ED been admitted. PMID- 8442549 TI - The incidence of battery in an urban emergency department. AB - STUDY OBJECTIVE: To determine the incidence of battery against emergency department medical staff by patients or visitors. DESIGN: Prospective descriptive study over a nine-month period. SETTING: A university-affiliated ED Level I trauma center with an annual census of approximately 64,000 located in a major metropolitan area. PARTICIPANTS: All staff members who had been punched, kicked, grabbed, pushed, or spat on by a patient or visitor while on duty in the ED. INTERVENTIONS: Questionnaire that was completed after the incident. RESULTS: During the study period, there were 19 instances of violence against staff by patients. Staff members were punched six times, kicked seven times, grabbed three times, pushed once, and spat on twice. Blows usually were sustained on the face or head (seven) or on the extremities (seven). In only four cases were hospital incident reports filled out, and in no case was there an injury serious enough to require ED treatment or disability leave. The assailant was usually male (15 of 19, 79%) and usually on a psychiatric or substance abuse detainment (15 of 19, 79%). CONCLUSION: This study suggests that instances of battery in an urban university hospital ED usually are not serious and are committed by patients on a psychiatric or substance abuse detainment. PMID- 8442550 TI - Emergency department satisfaction: what matters most? AB - STUDY OBJECTIVE: To determine the relative importance of variables correlated with patient satisfaction with emergency department care and service. DESIGN: Retrospective telephone survey targeting all patients who visited the Panorama City Kaiser Permanente ED from April 4 to April 17, 1991. Patients were contacted within one week of their discharge from the ED or hospital. PARTICIPANTS: Two hundred fifty-eight ED patients completed telephone surveys. Fifty-one percent of the respondents were male, and the mean age was 53 years. The majority of the respondents were white (70%); the most common service received was medical (82%). MEASUREMENTS AND RESULTS: Of the 14 variables that were found to be correlated with overall ED satisfaction, a multiple regression analysis revealed that the five most important variables were patient satisfaction with the amount of time it took before being cared for in the ED; patients' ratings of how caring the nurses were, how organized the ED staff was, and how caring the physicians were; and patient satisfaction with the amount of information the nurses gave them about what was happening to them. CONCLUSION: The total time patients spend in the ED and patients' perceptions of their wait time for an ED bed are not as important to patient satisfaction as is receiving prompt and caring service. The above service variables are key areas that may be targeted to improve ED services. PMID- 8442551 TI - Diagnostic ultrasonography in the emergency department. PMID- 8442552 TI - Diagnostic ultrasound imaging by physicians of first contact: extending the family medicine experience into emergency medicine. PMID- 8442553 TI - The origins, benefits, harms, and implications of emergency medicine clinical policies. AB - Emergency physicians desire to provide their patients with care that is of the highest quality and is cost effective. Any tool that promotes these aims is good and should be used. Clinical policies have been proposed as a new method of prompting physicians to provide better care. While there is no direct evidence that emergency medicine clinical policies improve care, there is indirect evidence that they may be useful. ACEP has initiated a process for the development and evaluation of selected clinical policies. We anxiously await information that sheds light on the value of policies in enhancing the clinical practice of emergency medicine. PMID- 8442554 TI - Massive ingestion of sustained-release verapamil with a concretion and bowel infarction. AB - Gastric concretions secondary to a drug overdose are uncommon but potentially fatal if not recognized and treated. They may continue to release drug into the stomach for hours or days after the ingestion, complicating diagnosis and treatment. We describe the case of a man with the previously unreported association of bowel infarction with a verapamil ingestion and concretion. This case illustrates the need for a heightened awareness of this potential complication. PMID- 8442555 TI - Gastrointestinal tract perforation with charcoal peritoneum complicating orogastric intubation and lavage. AB - A rare complication of gastric decontamination occurred in a young woman undergoing treatment for tricyclic ingestion. After orogastric intubation and lavage, she developed an acute abdomen and underwent laparotomy. Charcoal was discovered throughout the peritoneum, but concurrent and subsequent efforts failed to localize a specific perforation site. Her hospital course was protracted and complicated by tenacious peritoneal charcoal deposition, persistent peritonitis, and adhesion and abscess formation. She underwent both percutaneous and open abscess drainage, oophorectomy, and small-bowel resection. She required total parenteral nutrition in addition to feeding jejunostomy. This present case constitutes the first report of the clinical consequences of charcoal peritoneum. Outright viscus perforation should be considered among potential complications of orogastric intubation and lavage in the poisoned patient. Methods to minimize risks of its occurrence are suggested. PMID- 8442556 TI - Respiratory arrest following intramuscular ketamine injection in a 4-year-old child. AB - A healthy 4-year-old boy presented to the pediatric emergency department after inserting a black-eyed pea into his right external ear canal. Initial attempts at removal of this foreign body were unsuccessful, resulting in patient agitation. After administration of intramuscular ketamine for sedation, the patient was observed to experience one ineffective respiration followed by a period of apnea. No excessive oropharyngeal secretions or laryngospasm were noted. Spontaneous respirations resumed after 40 seconds, and the child recovered with no apparent ill effects. This case illustrates the need for adequate monitoring and preparation for emergency airway management when using ketamine for sedation in the ED. PMID- 8442557 TI - Intravenous magnesium for acute asthma. PMID- 8442558 TI - Intravenous magnesium for acute asthma. PMID- 8442559 TI - Intravenous magnesium for acute asthma. PMID- 8442560 TI - Intravenous magnesium for acute asthma. PMID- 8442561 TI - Intravenous magnesium for acute asthma. PMID- 8442562 TI - The use of pediatric sedation and analgesia. American College of Emergency Physicians. PMID- 8442563 TI - Emergency physician overhead. American College of Emergency Physicians. PMID- 8442564 TI - Immunization of the pediatric patient. American College of Emergency Physicians. PMID- 8442565 TI - Clinical policy for the initial approach to children under the age of 2 years presenting with fever. American College of Emergency Physicians. PMID- 8442566 TI - Adolescent (in)vulnerability. AB - Three groups of subjects were asked to judge the probability that they and several target others (a friend, an acquaintance, a parent, a child) would experience various risks. Subjects were middle-class adults, their teenage children, and high-risk adolescents from treatment homes. All three groups saw themselves as facing somewhat less risk than the target others. However, this perception of relative invulnerability was no more pronounced for adolescents than for adults. Indeed, the parents were viewed as less vulnerable than their teenage children by both the adults and those teens. These results are consistent with others showing small differences in the cognitive decision-making processes of adolescents and adults. Underestimating teens' competence can mean misdiagnosing the sources of their risk behaviors, denying them deserved freedoms, and failing to provide needed assistance. PMID- 8442567 TI - Successful adolescent development among youth in high-risk settings. AB - A new, interdisciplinary paradigm is emerging in developmental psychology. It includes contextual as well as individual variation and is more consonant with the complexity of adolescent behavior and development than traditional research paradigms. Social problems, such as poverty and racial discrimination, and the ways that young people negotiate adolescence successfully, are objects of research. A research program sponsored by the MacArthur Foundation, that embodies the new paradigm, is described. PMID- 8442568 TI - Adolescent mental health. Prevention and treatment programs. AB - Adolescent mental health represents a neglected area of research. Mental health objectives include the promotion of optimal functioning as well as the prevention and reduction of maladaptive functioning. This article examines behaviors and conditions that place adolescents at risk for adverse outcomes and the urgent need for prevention and treatment to promote adaptive functioning. The current status of prevention and treatment programs is discussed along with critical issues including the interrelation and contribution of both prevention and treatment; the interplay of basic and applied research; and the need to extend existing interventions as well as to devise new models to address underserved, understudied, and high-risk populations. Research on the role of adolescent development, paths toward adjustment and maladjustment, and special opportunities that adolescence presents for intervention are also discussed. PMID- 8442569 TI - Psychology's role in the public health response to assaultive violence among young African-American men. AB - African-American male adolescents face disproportionate risk for death or injury resulting from assaultive violence. This article presents a public health framework for examining the problem and developing interventions. A brief interdisciplinary review of research is provided on the nature and extent of the problem, its etiology, and current approaches to prevention. Attention is called to intra- and intergroup differences in patterns among White and ethnic minority youth and to specific theories and research about assaultive violence among young African-American men. Emerging imperatives in the search for solutions are identified, emphasizing the need for cultural sensitivity in the design of preventive interventions and an expanded role for psychologists in the public health response to this critical health problem. PMID- 8442570 TI - Depression in adolescence. AB - Adolescence is an important developmental period for understanding the nature, course, and treatment of depression. Recent research concerned with depressive mood, syndromes, and disorders during adolescence is reviewed, including investigations of the prevalence, course, risk factors, and prevention and treatment programs for each of these three levels of depressive phenomena in adolescence. A broad biopsychosocial perspective on adolescent depression is recommended, and possible directions for future integrative research are proposed. Based on current research and knowledge, implications for research, program, and national policy are considered. PMID- 8442571 TI - Adolescent suicide prevention. Current research and social policy implications. AB - The rate of adolescent suicide has increased dramatically in the past few decades, prompting several interventions to curb the increase. Unfortunately, many of the intervention efforts have not benefited from current research findings because the communication between researchers and those who develop the interventions is inadequate. Of specific concern are the increasingly popular curriculum-based suicide prevention programs, which have not demonstrated effectiveness and may contain potentially deleterious components. This article reviews the current epidemiological research in adolescent suicide and suggests how this knowledge could be used more effectively to reduce the rate of adolescent suicide. Recommendations include support for integrated primary prevention efforts; suicide prevention education for professionals; education and policies on firearm management; education for the media about adolescent suicide; more efficient identification and treatment of at-risk youth, including those exposed to suicidal behavior; crisis intervention; and treatment for suicide attempters. PMID- 8442572 TI - A congressional view of youth suicide. AB - Concern about adolescent suicide is pervasive among American teenagers. This article reviews the results of a national survey of adolescents about their knowledge of, and attitudes toward, youth suicide. More than 60% of teens surveyed reported knowing another teen who had attempted suicide and 6% reported having made an attempt themselves. The survey also provides information about adolescents' explanations for self-destructive behavior. Given this information, recommendations for effective preventive interventions and policy decisions are offered. PMID- 8442573 TI - Priorities for research on adolescent development. AB - Research on the development of adolescents has made significant progress in the past 10-15 years, but is not yet fully mature. Future research must (a) deepen the recent work in understanding normal adolescent development, particularly among American youth from understudied racial and ethnic minority groups and through more longitudinal studies; (b) balance pressures to implement urgent preventive interventions for adolescents with the need for systematic evaluations that will lead to improvements in these approaches, including those that promote healthy patterns in all adolescents and target clusters of health-compromising behaviors rather than single ones; and (c) identify specific features of the range of settings in which adolescents participate that do or do not foster healthy development. PMID- 8442574 TI - Adolescent Health. Reflections on a report to the U.S. Congress. AB - The Office of Technology Assessment (OTA) found that the conventional wisdom that American adolescents are so healthy that they do not require health and related services is not justified; U.S. adolescents often face formidable barriers to obtaining needed health care, and relatively little appropriate attention has been paid to adolescents by the federal government. OTA suggested that Congress could act to (a) increase adolescents' access to health care by supporting comprehensive health services specifically for adolescents, (b) restructure the federal role in adolescent health by creating an office of adolescent health in the U.S. Executive Branch, and (c) improve adolescents' social environments by providing more support to families of adolescents, limiting adolescents' access to firearms, supporting the expansion of their recreational opportunities, and further increasing opportunities for community service. Federal actions taken since OTA's report are summarized. PMID- 8442575 TI - Adolescence. Special issue. PMID- 8442576 TI - The opportunities of adolescence--research, interventions, and policy. Introduction to the special issue. PMID- 8442577 TI - American Psychological Association Commission on Violence and Youth. PMID- 8442578 TI - Development during adolescence. The impact of stage-environment fit on young adolescents' experiences in schools and in families. AB - Although most individuals pass through adolescence without excessively high levels of "storm and stress," many do experience difficulty. Why? Is there something unique about this developmental period that puts adolescents at risk for difficulty? This article focuses on this question and advances the hypothesis that some of the negative psychological changes associated with adolescent development result from a mismatch between the needs of developing adolescents and the opportunities afforded them by their social environments. It provides examples of how this mismatch develops in the school and in the home and how it is linked to negative age-related changes in early adolescents' motivation and self-perceptions. Ways in which more developmentally appropriate social environments can be created are discussed. PMID- 8442579 TI - Asthma in pregnancy. PMID- 8442580 TI - Circadian variation in airway responsiveness to methacholine, propranolol, and AMP in atopic asthmatic subjects. AB - Increased airway hyperresponsiveness is thought to be one of the phenomena underlying nocturnal airway obstruction in asthma. To investigate the mechanisms that influence and modulate this phenomenon, we compared circadian variations in airway responsiveness with AMP and propranolol with the circadian variation in airway responsiveness to methacholine. Inhalation provocation tests were performed at 16.00 and 04.00 h in 16 nonsmoking atopic asthmatic subjects (18 to 42 yr of age), prospectively assigned to Group 1 (mean circadian peak expiratory flow rate [PEFR] variation > or = 15%) and Group 2 (< 15%). The circadian change in airway responsiveness to AMP, in contrast to methacholine, was significantly related to the circadian PEFR-variation of the 16 subjects (r = 0.81, p < 0.001). In Group 1 (n = 7) geometric mean PC20 AMP decreased more than PC20 methacholine during the night (2.3 and 0.9 doubling concentrations respectively, p < 0.05), whereas no difference in baseline FEV1 was found at the same time points during the different study days. Geometric mean PC20 propranolol did not change during the night. Daytime PC20 propranolol and PC20 AMP, in contrast to PC20 methacholine, were significantly lower in Group 1 as compared with Group 2. Together, the results show a higher susceptibility to stimulation of "indirect" airway responsiveness in the subjects with increased circadian PEFR amplitude. This suggests that mast cell activation rather than primary changes in smooth muscle cell contraction may play a role in the development of nocturnal airway obstruction. PMID- 8442581 TI - Theophylline--an immunomodulatory role in asthma? AB - Theophylline, a drug used for the treatment of asthma, is recognized as an immunomodulator affecting T-lymphocytes both in vitro and in vivo. The effect of slow-release theophylline (Uniphyllin Continus) on the late asthmatic response (LAR) has been compared with placebo before and after 5 wk of treatment in a double-blind, randomized, parallel group study. Nineteen volunteers with stable mild asthma successfully completed the study. All were dual responders with a documented late response to inhaled house dust mite extract. The LAR was assessed both in terms of changes in lung function and in peripheral blood T-lymphocyte subsets. The mean (SEM) maximal late fall in FEV1 before and after treatment was 28.8 (4.1)% and 7.8 (2.0)% with theophylline, versus 35.8 (5.1)% and 29.1 (5.0)% with placebo (p = 0.046; Cl, 0.3-26.9). Corresponding figures for specific airway conductance (SGaw) were 46.4 (8.4)% and 7.2 (8.0)% with theophylline versus 46.2 (7.2)% and 44.8 (7.7)% with placebo (p = 0.008; Cl, 11.2 to 64.1). This was achieved at a mean (SD) trough serum theophylline level of only 7.8 (3.5) micrograms/ml. Airway responsiveness to methacholine was not significantly changed 24 h after the initial allergen challenge. There was a trend towards a decrease in baseline responsiveness after treatment with theophylline compared with that after placebo (p = 0.07). Studies of peripheral blood lymphocytes showed a modifying effect of treatment on the allergen-induced changes in CD4 and CD8 counts 48 h after challenge. Previous studies have shown a protective effect of theophylline on the LAR at serum theophylline concentrations within the conventional range for bronchodilation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8442582 TI - Deposition in asthmatics of particles inhaled in air or in helium-oxygen. AB - Ten subjects with asthma inhaled 3.6 micron particles labeled with 111In in air and in a helium-oxygen mixture (He-O2) at 0.5 and at 1.2 L/s. Lung retention was measured after zero and after 24 h, and the percentage 24-h retention (Ret24) was taken to represent the fraction deposited in the alveolar part of the lung. For both inhalation rates, Ret24 was significantly higher when particles were inhaled with He-O2 than with air. The increase in Ret24 seemed to be larger in subjects with asthma than in healthy persons earlier studied. Ret24 was correlated with changes in both large and small airways, especially when the particles were inhaled with He-O2. Our data suggest that inhalation of drugs in He-O2 might be of therapeutic value when treating patients with severely obstructed airways. PMID- 8442583 TI - Functional characteristics of bronchial epithelium obtained by brushing from asthmatic and normal subjects. AB - Airways epithelial cells may be involved in the pathogenesis of asthma, but their role remains to be determined. Epithelial cells can release large amounts of 15 hydroxy-eicosatetranoic acid (15-HETE) and smaller amounts of prostaglandin E2 (PGE2) as well as fibronectin, a mediator involved in epithelial repair after injury. Epithelial cells obtained after bronchial brushing of 16 asthmatic (age 38 +/- 5 yr) and 11 normal subjects (age 36 +/- 5 yr) were studied. The percentage of epithelial cells was assessed by immunocytochemistry using an anti cytokeratin antibody. The viability of the cells was assessed by trypan blue exclusion. The release of 15-HETE PGE2 and fibronectin was studied in resting cells and after A23187 calcium ionophore stimulation. Epithelial cells always comprised more than 86% of cells recovered, and the viability of epithelial cells was significantly (p < 0.001, Mann-Whitney U test) greater in normal subjects (54 +/- 5%) compared with asthmatic subjects (13 +/- 1%). The release of 15-HETE and fibronectin by resting epithelial cells was significantly greater in asthmatics (p < 0.05, Mann-Whitney U test) than in normal subjects. A23187 significantly (p < 0.05, Wilcoxon W test) increased the release of 15-HETE and fibronectin. There was no significant difference in the release of PGE2 by resting cells from either asthmatics or normal subjects, but challenge with A23187 induced a significant (p < 0.03, Wilcoxon W test) increase in PGE2 from cells of asthmatics but not from cells of normal subjects. This study shows that epithelial cells are activated and less viable in asthma and suggests a role for these cells in asthma. PMID- 8442584 TI - Collateral ventilation and gas exchange during airway occlusion in the normal human lung. AB - The effectiveness of collateral ventilation in maintaining alveolar gas tensions in obstructed lung segments was investigated using fiberoptic bronchoscopy to place an occluding catheter-tip balloon in selected lobar and segmental bronchi in supine normal human subjects. Gas tensions from beyond the occlusion were measured with a respiratory mass spectrometer. Collateral ventilation is known to be minimal between lobes; therefore, values measured in obstructed lobes provide a control. No significant difference was found between the partial pressures of oxygen or carbon dioxide measured in obstructed lobes and in obstructed segments. In both cases respiratory gas tensions approached reported values for mixed venous levels. The time taken to attain a steady state of gas composition in the obstructed lung was rapid (approximately 50 s), and it was no different for lobes and segments. In addition, collateral ventilation was assessed by measuring the amount of helium reaching occluded lobes and segments when subjects breathed a mixture of 21% oxygen and 79% helium. The rate of rise in helium concentration was less than 1%/min in both lobes and segments, a figure that may be explained by delivery of helium in recirculated blood rather than by collateral ventilation. We conclude that intersegmental collateral ventilation has a negligible role in the maintenance of alveolar gas tensions in supine normal humans during tidal breathing. PMID- 8442585 TI - Effect of anti-IL-5 and IL-5 on airway hyperreactivity and eosinophils in guinea pigs. AB - Chronic ovalbumin challenge of sensitized guinea pigs induces bronchoalveolar lavage (BAL) eosinophilia, neutrophilia, and tracheal hyperreactivity. In the present study, the influence of monoclonal antibody to murine interleukin-5 (anti IL-5) on these phenomena is examined. In ovalbumin-sensitized guinea pigs treated with isotype-matched control antibody and challenged daily with ovalbumin for 8 days, the number of BAL eosinophils and neutrophils is increased significantly six- and fivefold, respectively, compared with saline-challenged animals. The maximal contractions of tracheal rings to histamine and arecoline in ovalbumin challenged animals are enhanced significantly to 155% compared with saline challenged animals. In sensitized guinea pigs treated with anti-IL-5, the BAL eosinophil number is markedly inhibited compared with control antibody treatment in both saline- and ovalbumin-challenged animals. In contrast, the number of neutrophils is not affected by anti-IL-5 treatment. In guinea pigs treated with anti-IL-5, the development of hyperreactivity to histamine and arecoline after ovalbumin challenge is completely inhibited. The contractions to histamine and arecoline of tracheal rings isolated from guinea pigs treated with recombinant murine IL-5 for 3 or 7 days are enhanced significantly to approximately 140% compared with controls. Treatment with IL-5 for 7 days tends to increase the number of eosinophils in BAL fluid. It can be concluded that IL-5 is involved in airway eosinophilia and in the development of hyperreactivity in this animal model, but other cytokines may contribute. Development of IL-5 synthesis inhibitors and/or receptor antagonists could provide another therapeutic class of anti-asthma drugs. PMID- 8442586 TI - Airway responsiveness to adenosine 5'-monophosphate in chronic obstructive pulmonary disease is determined by smoking. AB - In contrast to methacholine, a stimulus that induces airway constriction mainly by "direct" stimulation of airway smooth muscle cells, AMP airway responsiveness reflects "indirectly" induced airway narrowing via inflammatory or neural reflex mechanisms. In order to determine inflammatory contribution to airway narrowing in COPD, we performed AMP and methacholine inhalation provocation tests in nonatopic subjects with COPD and compared the results with those obtained from atopic nonsmoking asthmatics and from healthy smoking volunteers. AMP caused airway narrowing in all but two subjects with COPD and in only three of the 12 healthy smoking subjects. Patients with COPD were significantly more responsive to AMP and methacholine than were healthy smoking volunteers. Geometric mean PC20 AMP was significantly lower in the smokers with COPD (7.2 mg/ml) than in the nonsmokers with COPD (58.5 mg/ml), whereas PC20 methacholine values and baseline FEV1 were comparable. In the nonatopic nonsmoking subjects with COPD, PC20 AMP was significantly higher than in the atopic nonsmoking asthmatics (3.8 mg/ml), whereas they responded similar to methacholine provocation. These results indicate that most subjects with COPD respond to AMP provocation and that smoking determines the degree of airway responsiveness to AMP in COPD. We suggest that increased susceptibility to mediator release by mast cells or neural reflex mechanisms are involved in AMP-induced airway constriction in asthma and in COPD. PMID- 8442587 TI - Neuronal M2 muscarinic receptor function in guinea-pig lungs is inhibited by indomethacin. AB - The function of M2 muscarinic autoreceptors on pulmonary parasympathetic nerves was investigated in the absence and presence of cyclooxygenase inhibitors in vivo. Guinea pigs were anesthetized, paralyzed, and artificially ventilated. Pulmonary inflation pressure, heart rate, and blood pressure were recorded. Electrical stimulation of vagus nerves produced bronchoconstriction (measured as an increase in pulmonary inflation pressure) and bradycardia. In control guinea pigs, pilocarpine (1 to 100 micrograms/kg) given intravenously stimulated inhibitory M2 muscarinic receptors on pulmonary parasympathetic nerves, thus attenuating vagally induced bronchoconstriction. Conversely, blockade of these autoreceptors by the selective M2 antagonist gallamine (0.1 to 10 mg/kg given intravenously) potentiated vagally induced bronchoconstriction. Separate groups of animals were given either indomethacin or naproxen. These cyclooxygenase inhibitors potentiated vagally induced bronchoconstriction. Furthermore, in those animals pretreated with either indomethacin or [+] naproxen, pilocarpine did not inhibit and gallamine did not potentiate vagally induced bronchoconstriction. In the heart, the effects of pilocarpine and gallamine on M2 muscarinic receptors were not altered by either cyclooxygenase inhibitor. Neither intravenously administered indomethacin (1 mg/kg) nor [+] naproxen (5 mg/kg) altered baseline pulmonary inflation pressure or baseline heart rate in the treated guinea pigs. These studies demonstrate that inhibitory M2 muscarinic receptors on pulmonary parasympathetic nerves do not function in the presence of cyclooxygenase inhibitors. Loss of M2 receptor function may contribute to aspirin-induced airway hyperresponsiveness. PMID- 8442588 TI - Reactivity to cold-air hyperventilation in normal and in asthmatic children in a survey of 5,697 schoolchildren in southern Bavaria. AB - The measurement of bronchial hyperreactivity (BHR) may give additional information to questionnaire-based studies of asthma prevalence. It is desirable to have a provocation method with high specificity that avoids the use of pharmacologic provocations in large numbers of healthy children. It was the aim of this study to establish a range of values for responsiveness to cold-air challenge in normal children, to describe its specificity and sensitivity for a diagnosis of asthma in a large unselected sample of schoolchildren in a field study, and to measure factors associated with hyperresponsiveness. All fourth grade schoolchildren (9 to 11 yr of age) in Munich and several southern Bavarian communities (n = 9,403) were surveyed with a questionnaire (response rate, 87%), baseline lung function, and cold-air hyperventilation challenge (n = 5,697). A diagnosis of asthma was reported in 7.9% of children. In the reference group, the ninety-fifth percentile (%ile) for the change of FEV1 (DFEV1) was -9.0%; the 90%ile was -7.3%. Asymptomatic children fulfilling all criteria for the reference group showed a significantly increased reactivity if they had a family history of asthma (p = 0.038). With a cutoff for DFEV1 of -9.0% or -7.3% the respective sensitivities to "detect" a diagnosis of asthma were 21.6 and 30.7%, and for asthma with symptoms during the previous 12 months it was 26.2 and 35.1%. Reactivity to cold air increased with the number of episodes of asthma in the previous 12 months. In a multiple linear regression model, factors associated with increased reactivity to cold air were diagnosed asthma, hay fever, male sex, younger age, and a positive skin test.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8442589 TI - Sensitization and exposure to indoor allergens as risk factors for asthma among patients presenting to hospital. AB - To investigate the role of indoor allergens in adult patients with acute asthma, we conducted a case-controlled study on patients presenting to an emergency room. One hundred and fourteen patients and 114 control subjects were enrolled over a 1 yr period in Wilmington, Delaware. Sera were assayed for total IgE, and for IgE antibodies to dust mites, cat dander, cockroach, grass pollen, and ragweed pollen. Dust was obtained from 186 homes and assayed for dust mite, cat, and cockroach allergens. IgE antibodies to mite, cat, and cockroach were each significantly associated with asthma, and this association was very strong among participants without medical insurance and among African Americans. Among 99 uninsured participants, sensitization to one of the indoor allergens (> 200 RAST units) was present in 28 of 57 asthmatics and in one of 42 control subjects (odds ratio, 39; confidence interval, 9.4 to 166). For cat and cockroach the combination of sensitization and presence of allergen in the house was significantly associated with asthma. Furthermore, there was a strong inverse relationship between IgE antibodies to cat and to cockroach, and the risk of this sensitization was in large part restricted to homes or areas with high levels of allergen. Thirty-eight percent of the asthmatics, but only 8% of the control subjects, were allergic to one of the three indoor allergens, and had high levels of the relevant allergen in their houses (odds ratio, 7.4; confidence interval, 3.3 to 16.5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8442590 TI - Airway obstruction and ventilation-perfusion relationships in acute severe asthma. AB - We have investigated the time course of ventilation-perfusion (VA/Q) mismatch and airflow obstruction in 18 patients with acute severe asthma with the objective to identify potential differences according to the clinical severity of the attacks. Nine patients were hospitalized and nine were discharged (emergency room stay < 24 h) according to the clinical criteria of the attending physicians. Spirometry and VA/Q inequality (multiple inert gas technique) were measured within the first 6 h of treatment in the emergency room, and at Weeks 1,2,3, and 4 thereafter. In the emergency room [corrected] hospitalized patients (in relation to those discharged) showed lower airflow rates (FEV1, 31 +/- 3 versus 46 +/- 6% predicted SEM) and greater VA/Q mismatch (as assessed by the dispersion of blood flow distributions (logSD Q) (1.28 +/- 0.11 versus 0.92 +/- 0.11; normal values < 0.6). Even though the rate of improvement of airflow was similar in both groups (without returning to normal limits), VA/Q relationships improved at different rates in each group and reached normal values at the end of the study. Although in hospitalized patients the recovery of VA/Q abnormalities was delayed in relation to airflow rates, the time course in discharged patients was the same. Previous studies have shown a dissociation between spirometry and VA/Q inequality, suggesting that whereas airflow rates predominantly reflect bronchoconstriction of large airways, VA/Q mismatch is more related to obstructive changes in peripheral airways. Our results support this hypothesis and suggest that the more severe the asthma attacks, the more severe the obstructive changes involving peripheral airways for a given degree of widespread airway narrowing. PMID- 8442591 TI - Survival of patients with chronic obstructive pulmonary disease receiving long term domiciliary oxygen therapy. AB - Previous trials, in which 76 to 100% of the patients were men, have shown a varied survival time in chronic obstructive pulmonary disease treated with long term domiciliary oxygen therapy. We have analyzed predictors of survival in chronic obstructive pulmonary disease, including sex-related differences in survival in 403 patients (201 men) registered in a national register when starting long-term oxygen therapy between January 1, 1987 and June 30, 1989. This register covers the whole of Sweden with a population of 8.4 million. Some 90% of all the patients receiving long-term oxygen therapy are included. Lung function and performance status predicted survival during oxygen therapy in men, whereas a poor performance status and the presence of orally administered steroid medication predicted poor survival in women. Oral steroid medication use was correlated with an increased mortality rate in women (relative risk of death, 2.13; 95% confidence interval, 1.38 to 3.29; p < 0.001) and showed no tendency to improve survival in men. In patients not receiving oral steroids, women had a lower mortality rate than did men (relative risk of death, 0.58; 95% confidence interval, 0.39 to 0.97; p < 0.05). Our data indicate that in patients not receiving oral steroid medication, women have a better survival than do men. An increased mortality was found in women receiving oral steroid medication which might be caused by an increased susceptibility to the side effects of oral steroids. PMID- 8442592 TI - Muscular metabolism during oxygen supplementation in patients with chronic hypoxemia. AB - The effects of supplemental oxygen (O2) versus air on working calf muscle metabolism were studied in seven patients with stable chronic obstructive pulmonary disease (COPD) and chronic hypoxemia (PaO2 = 57 +/- 3 SE mm Hg) and seven age-matched control subjects. Oxygen and air were randomly administrated at 24-h intervals, and O2 flow rate was adjusted to correct hypoxemia (PaO2 = 87 +/- 4 mm Hg) in the COPD group. The relative concentrations of ATP, phosphocreatine (PCr), inorganic phosphate (Pi), phosphomonoesters (PME), and the intracellular pH (pHi) were determined with 31P magnetic resonance spectroscopy at rest, during a graded standardized and localized exercise protocol (360 active plantar flexions), and during recovery. In resting muscle no significant effect of added O2 was demonstrable in each group with regard to pHi, Pi/PCr, and ATP/(PCr+Pi+PME) ratios. Mechanical data were similar between the two groups and between the two tests during the whole exercise. The indices of muscular oxidative metabolism (Pi/PCr and pHi at the end of exercise and recovering PCr resynthesis rate) were impaired in the COPD group compared with that in the control group during air (all p < 0.05). All these parameters were significantly improved with added O2 in the COPD group (p < 0.05), whereas no similar effects were observed in the control group. However, these beneficial effects were incomplete since the exercising Pi/PCr ratio remained higher in the COPD group than in the control group during added O2. This energetic muscular impairment could correspond to tissular damage related to chronic hypoxemia. PMID- 8442593 TI - Prediction equations for single-breath carbon monoxide diffusing capacity from a Chinese population. AB - Most available prediction equations for the single breath carbon monoxide diffusing capacity, or DLCO, are based on white populations and do not account for racial differences. We performed this test on 436 Chinese adults. The method of measurement essentially followed the American Thoracic Society recommendations. Data on 306 subjects who had two technically acceptable test results provided prediction equations and upper and lower 95% confidence limits for healthy nonsmokers. Simple linear equations using age, height, and body weight as independent variables were generated and compared with nonlinear models. The use of nonlinear models did not add to the predictability of standard linear regressions. The distribution of residuals (predicted-measured values) was Gaussian with simple linear regressions. A comparison of predicted values for DLCO, calculated from different equations in an independent group of healthy subjects, revealed that the present set of equations had the smallest residual mean and standard deviation rankings compared with other equations for white subjects. These are the first DLCO equations proposed for Chinese men and women aged 20 to 70 yr. The predicted values from this study for DLCO and alveolar volume (VA), were significantly lower than those of most equations for white subjects, but were not for DLCO/VA. Although a portion of the differences may be explained by the additive effects of technical factors, the discrepancies can also be attributed to the smaller body size in this ethnic group, and consequently to the smaller lung volumes. Equations derived from whites, with inclusion of smokers, provided predicted values comparable to, or even lower than, those from this study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8442594 TI - Respiratory muscle acidosis stimulates endogenous opioids during inspiratory loading. AB - Activation of endogenous opioid pathways during intense inspiratory flow resistive loading (IRL) results in greater inhibition of EMG activity in the external oblique (EMGeo) relative to the diaphragm (EMGdi). Dichloroacetate (DCA) abolishes opioid-mediated inhibitory influences upon these muscles, suggesting a causal relationship between respiratory muscle lactic acidosis and activation of endogenous opioid pathways, during IRL. We tested the hypothesis that a more intense acidosis of the external oblique relative to the diaphragm may be the signal that determines the differential inhibitory opioid-mediated effect upon the respiratory muscles during IRL. Unanesthetized goats were exposed to IRL (50 cm H2O/1/s) for 120 min, before and after intravenous pretreatment with DCA (50 mg/kg) or saline. We measured peak phasic EMGdi and EMGeo, and respective muscle interstitial pH (pHdi, pHeo) using flexible pH probes. After 120 min IRL with saline, pHdi, and pHeo declined by -0.12 +/- 0.03 (mean +/- SEM) and -0.20 +/- 0.04 units, respectively (p < 0.05, pHdi versus pHeo). Naloxone (NLX), 0.3 mg/kg given intravenously at this time, increased EMGdi by 26.5 +/- 6.1%, but EMGeo by 81.9 +/- 13.3% (p < 0.05, EMGdi versus EMGeo). DCA blunted both the change in pHdi and pHeo during IRL (to -0.01 +/- 0.01 and -0.08 +/- 0.03 units, respectively) (p < 0.05, DCA versus saline) and the increase in EMGdi and EMGeo with NLX (to -1.0 +/- 2.6% and 5.7 +/- 5.8%, respectively) (p < 0.05, DCA versus saline).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8442595 TI - The effect of respiratory and lactic acidosis on diaphragm function. AB - The relative effects of respiratory and metabolic acidosis on diaphragm function are not known. To determine these effects, we compared the effects of respiratory and lactic acidosis on the contractile properties of the diaphragm. We estimated diaphragmatic performance from the change in transdiaphragmatic pressure after supramaximal stimulation of the phrenic nerves in an open-chested, casted-abdomen dog. Similarly, we stimulated the gastrocnemius motor nerve and examined force production and relaxation rate to determine if there was a difference in the response of this skeletal muscle. There was a fall in diaphragm performance with respiratory acidosis (77.1 +/- 16.9 cm H2O versus 93.8 +/- 15.0 cm H2O baseline), but not with lactic acidosis (96.7 +/- 15.7 cm H2O versus 93.8 +/- 15.0 cm H2O baseline); and the gastrocnemius was unaffected by either acidosis. The changes with respiratory acidosis were similar to those seen with diaphragmatic fatigue and had similar relaxation rate changes, suggesting that intracellular pH may play a mechanistic role in respiratory muscle fatigue. In addition, the absence of a respiratory acidosis effect on a non-diaphragmatic skeletal muscle's function represents another physiologic difference between the diaphragm and other skeletal muscles. PMID- 8442596 TI - Effects of nasal airflow on breathing during sleep in normal humans. AB - The nasal airway is a common route for oxygen delivery to hypoxemic patients, and it has been advocated as a suitable route for intermittent positive pressure ventilation to patients in respiratory failure. There is, however, conflicting evidence on the question of whether nasal airflow has a stimulant or a depressant effect on ventilation. We therefore studied the effects on ventilation of increasing and decreasing nasal airflow during sleep, thereby avoiding the voluntary and behavioral influences on breathing seen during wakefulness. After an acclimatization night, each of nine normal male volunteers (20 to 28 yr of age) underwent overnight sleep studies using standard techniques. Each sleep study had three phases of at least 2-h durations: (1) control nasal breathing (CNB); (2) added nasal flow of 4 L of compressed air via nasal prongs (ANF); (3) predominant mouth breathing (PMB). Significant differences were found by ANOVA for the three experimental periods for both minute ventilation (Vl) and mean inspiratory flow rate (VT/Tl) during Stage 2 sleep, with the highest values occurring during ANF. Vl was 5.40 +/- 0.58 L/min (mean +/- SD) during ANF, 5.35 +/- 0.82 during CNB, and 4.92 +/- 0.71 during PMB (p < 0.05 by ANOVA). VT/Tl was 266 +/- 23 ml/s during ANF, 248 +/- 39 during CNB, and 241 +/- 30 during PMB (p < 0.02 by ANOVA). VT also tended to be higher during ANF (p < 0.1 by ANOVA). Respiratory frequency did not differ significantly during the three study periods. There was insufficient slow-wave and REM sleep to allow ventilatory comparisons in these sleep stages.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8442598 TI - Nasal continuous positive airway pressure in chronic heart failure with sleep disordered breathing. AB - Nasal continuous positive airway pressure (NCPAP) has been reported to improve daytime symptoms in patients with sleep disordered breathing due to heart failure. To examine this in a controlled manner, eight men with stable chronic heart failure (mean left ventricular ejection fraction 18% and mean frusemide dose 160 mg) were entered into a controlled trial of domiciliary nocturnal NCPAP. At polysomnography (with sleep apnea quantified as the number of > 4% dips in arterial saturation per hour), seven had nocturnal Cheyne-Stokes respiration (SaO2 dip rate 3 to 27/hr), and one both central and obstructive apneas (SaO2 dip rate 8/hr). After 2 wk nocturnal domiciliary NCPAP at < 1.5 cm H2O (placebo) and 7.5 cm H2O (active) in random order, bicycle exercise tolerance and heart failure symptoms (modified Likert questionnaire) were assessed by an observer unaware of the patients' NCPAP status. Pulse oximetry (all subjects) and radionuclide estimated left ventricular ejection fraction (three subjects) were also measured at the end of each period. Two subjects withdrew from the study because of worsening heart failure during active NCPAP (7.5 cm H2O), and one of these subjects died. In the remaining six subjects exercise tolerance, symptom scores, and the severity of sleep apnea were similar on active NCPAP compared with placebo. When it was measured, resting left ventricular ejection fraction was lower on active therapy than on placebo. These data exclude a 25% improvement in exercise tolerance with 95% confidence and suggest that a study of 160 subjects would be needed to exclude a 10% change in symptom score.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8442597 TI - Effect of anterior mandibular positioning on obstructive sleep apnea. AB - This prospective case report series utilized an anterior mandibular positioning (AMP) device on obstructive sleep apnea (OSA) patients and evaluated the changes in the respiratory disturbance index (RDI) and subjective overall satisfaction with the treatment. The RDI was based on all-night polysomnographic studies performed before and after approximately 4 months of appliance use. Overall satisfaction with the treatment was rated using a Likert scale (0 to 10) after 6, 18, and 36 months of AMP device use. Although only 15 of the 24 subjects agreed to undergo post-appliance polysomnograms, 14 of the 15 subjects showed a clear decrease in the RDI. The effect on the other subjects is unknown, but even if the 9 subjects without polysomnograms had no change in the RDI from the AMP device, a minimum rate of 58% of the subjects (14 of 24) would have substantially improved the RDI at the 3-month time point. Of the 24 subjects, 2 subjects claimed no immediate benefit and stopped using the device, 4 subjects were lost to followup, 1 subject lost weight and stopped using the device, 1 subject had mandibular advancement surgery after using the appliance for a period of time, and 3 stopped using the appliance because of persistent temporomandibular pain problems. The remaining 12 of the 23 (52%) original subjects were still using the appliance successfully at 36 months. One subject died of non-apnea-related causes before the 18-month follow-up time point. The 16 subjects who responded at 36 months reported a mean overall satisfaction with treatment of 6.9 +/- 3.3 on a scale of 10. PMID- 8442599 TI - Characteristics of the snoring noise in patients with and without occlusive sleep apnea. AB - We analyzed snoring noise from 10 nonapneic heavy snorers and nine patients with obstructive sleep apnea (OSA). Sound was recorded simultaneously through two microphones, one attached to the manubrium sterni and one suspended in the air 15 cm from the patient's head. Signals were stored on magnetic tape, digitized, and displayed in the time and frequency domains. Most of the power of snoring noise was below 2,000 Hz, and the peak power was usually below 500 Hz. When snores were generated during nose-only breathing (nasal snores), the sound spectrum was made up of a series of discrete, sharp peaks, with a fundamental note and harmonics similar to the spectrum of voiced sounds. When snores were generated during breathing through nose and mouth (oronasal snores), the spectra showed a mixture of sharp peaks and broad-band white noise. Patients with apnea showed a sequence of snores with spectral characteristics that varied markedly through an apnea respiration cycle. The first postapneic snore consisted mainly of broad-band white noise with relatively more power at higher frequencies, so that the ratio of power above 800 Hz to power below 800 Hz could be used to separate snorers from patients with OSA. Other breaths in the cycle resembled oronasal or nasal snores in nonapneic subjects. Characteristics of the noise give information about the possible mechanism of sound generation and thus about the behavior of the pharynx during snoring. Quality of snoring sound may help to separate patients with obstructive apnea from those with simple snoring. PMID- 8442600 TI - Diagnostic value of bronchoalveolar lavage in peripheral lung cancer. AB - A prospective study has been performed to assess the value of the addition of bronchoalveolar lavage (BAL) to the routine bronchoscopic exploration with bronchial washing (BW) and postbronchoscopy sputum (PBS) procedures in the diagnosis of peripheral primary lung cancer not visible through bronchoscope when fluoroscopic guidance is not available. BW, BAL, and PBS were performed in 67 patients with suspected primary lung cancer by peripheral lung lesion on chest radiograph (39 nodules and 28 infiltrates) and nonendoscopically visible lesion. The sequence of procedures was in all cases BW, BAL, and post-bronchoalveolar lavage bronchoaspirate (PBBA). An attempt was made to collect early morning postbronchoscopy samples of sputum (PBS) on 3 consecutive days. BW and PBBA were collected in the same test tube, and the cytologic result was considered as BW diagnostic yield. If there were negative bronchoscopic results, either percutaneous fine-needle aspiration or open-lung biopsy were performed for diagnosis. Fifty-five patients were found to have malignant disease (23 adenocarcinomas, 22 squamous cell carcinomas, six small cell carcinomas, and four bronchioloalveolar cell carcinomas). BAL was positive in 18 of the 55 (33%) carcinomas, and it gave the only positive result in six (11%). BW was also positive in 18 of the 55 (33%), but it gave positive results in only 3 (5%). PBS was positive in 13 of the 43 (30%) patients from whom samples could be spontaneously obtained and were suitable for cytologic examination (not consisting of saliva), and gave the only positive result in three (7%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8442601 TI - Decreased surfactant protein A in patients with bacterial pneumonia. AB - Abnormalities have been previously noted in the lipid content of the lavage fluid of patients with bacterial pneumonia. In order to determine if these changes were also seen in surfactant apoproteins, we studied levels of surfactant protein A (SP-A) in patients with bacterial pneumonia. Patients without human immunodeficiency virus who were being evaluated for pulmonary infiltrates underwent bronchoscopy with bronchoalveolar lavage (BAL). Twenty-two patients with pneumonia, 12 caused by gram-positive organisms (Gm+ PNEU) and 10 caused by gram-negative organisms (Gm- PNEU), were compared with 10 patients with idiopathic pulmonary fibrosis (IPF) and 11 control subjects (CON). The percentage of neutrophils in the BAL was significantly higher in the patients with IPF and the pneumonia groups than in the control group (CON: mean, 1; range, 0 to 3. IPF: mean, 26; range, 13 to 42). Gm+ PNEU: mean, 33; range, 8 to 99. Gm- PNEU: mean, 64; range, 10 to 92; p < 0.0001). The amount of SP-A in the BAL fluid was similar for the CON and the IPF groups (CON: mean, 15; range, 5.75 to 26.5 micrograms/ml BAL. IPF: mean, 18.4; range, 6.49 to 45.64 micrograms/ml), whereas both pneumonia groups had significantly less SP-A (Gm- PNEU: mean, 5.54; range, 0.58 to 12.7. G+ PNEU: mean, 1.93; range, 0.47 to 6.74; p < 0.001). There was significantly less SP-A in the Gm+ PNEU group than in the Gm- PNEU group (p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8442602 TI - Pulmonary complications of human immunodeficiency virus infection in Bujumbura, Burundi. AB - To determine the types of pulmonary disease associated with human immunodeficiency virus (HIV) infection, we conducted a prospective study of 302 consecutive patients admitted for acute respiratory disease to a university hospital in Bujumbura, Burundi. Diagnoses were made according to well-defined criteria. Of the total, 222 patients (73.5%) were HIV seropositive, with women younger than men. Features suggestive of underlying HIV infection were the clinical findings of oral thrush, peripheral lymphadenopathy, or herpes zoster and the radiographic abnormalities of hilar-mediastinal adenopathy or a reticulonodular infiltrate. Tuberculosis and community-acquired pneumonia occurred with approximately equal frequency in the HIV-seropositive and seronegative groups. Pneumocystis carinii pneumonia was diagnosed in 11 patients, all seropositive. Gram-negative bacteremia, especially Salmonella typhimurium, occurred in 23 seropositive patients (10.4%). A total of 24 seropositive patients died during the initial hospitalization, and 11 others required readmission; no seronegative patients died or were rehospitalized. We conclude that HIV infection is a major risk factor for the development of acute respiratory diseases in adults of sufficient severity to require hospitalization in Bujumbura. In this Central African country, where exposure to virulent bacterial pathogens is ubiquitous, tuberculosis, pneumonia, and salmonellosis occur with much greater frequency than classic AIDS-defining opportunistic infections or malignancies. PMID- 8442603 TI - Reduced antibody responses after immunization in rat lung transplants. AB - Pulmonary infections occur so frequently in recipients of lung transplants as well as of combined heart and lung transplants that it has been suggested that the function of the defense system in lung transplants is impaired. Therefore, we investigated in rats whether antibody responses against intrapulmonary antigens were impaired at various time points after transplantation. Antibody responses were induced in lungs of four experimental groups. Group 1: normal lungs (LEW); Group 2: hilar-stripped (sham-operated) lungs (LEW); Group 3: syngeneic lung transplants (LEW-to-LEW); Group 4: allogeneic lung transplants (BN-to-LEW). The operations were performed on the left lungs. All rats (including those with normal lungs) were treated with cyclosporine on Days 2 and 3 after operation, which treatment is adequate to induce permanent graft acceptance of the allografts. Rats were immunized 7, 10, 14, 21, and 28 days and at 6 months after operation with sheep red blood cells, injected selectively into the bronchus of the left lung. The resulting serum antibody titers were detected with a hemolysis assay. After immunization on Day 7, no antibody responses could be detected in all hilar-stripped and transplanted rats, whereas responses were normal in two allografted rats immunized in the nontransplanted right lung. After immunization on Day 14, responses had returned to normal in hilar-stripped rats, whereas they were still impaired in the transplanted rats. After immunization on Day 28, responses were almost normal in all rats and remained so until 6 months after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8442604 TI - Treatment responses to surfactants containing natural surfactant proteins in preterm rabbits. AB - The in vivo function of surfactants reconstituted using natural surfactant lipid and protein constituents was evaluated in 27-day-gestation preterm rabbits. The animals were treated with protein-free surfactant lipids (LH-20), LH-20 + 5% SP A, LH-20 + 1% SP-B, LH-20 + 1% SP-C, LH-20 + 5% SP-A + 1% SP-B + 1% SP-C (SP ABC), natural sheep surfactant, or 4 ml/kg 0.45% NaCl (control) and then ventilated with tidal volumes of 8 ml/kg and 3 cm H2O positive end-expiratory pressure (PEEP). Ventilatory pressures (peak pressures minus PEEP) and dynamic compliances of the LH-20 + SP-C rabbits were greater (p < 0.01) than those of control, LH-20, and LH-20 + SP-A groups but lower (p < 0.05) than in the LH-20 + SP-B, LH-20 + SP-ABC, and sheep surfactant groups. Recoveries of intravascular labeled albumin in the lungs were comparable in the LH-20 + SP-B, LH-20 + SP-C, LH-20 + SP-ABC, and sheep surfactant groups and less (p < 0.01) than in LH-20 + SP-A rabbits, which had lower (p < 0.05) recoveries than did the control and LH 20 groups. The postventilation pressure-volume curves for LH-20 + SP-B and LH-20 + SP-ABC rabbits had significantly lower opening pressures, larger maximal lung volumes, and larger retained volumes on deflation relative to the LH-20 + SP-C, LH-20, and control groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8442605 TI - Immunoglobulin E-mediated increase in vascular permeability correlates with eosinophilic inflammation. AB - An increase in bronchovascular permeability is thought to play an important role in the pathogenesis of allergic asthma. We sought to determine whether the increase in permeability observed 24 h after segmental antigen challenge in ragweed-allergic human volunteers was associated with the infiltration and degranulation of a specific cell type. A 20,000-fold range of antigen concentrations was used to alter the number and type of inflammatory cells recruited to the lung by challenge. Although large numbers of inflammatory cells were recruited to lung air spaces over a large range of antigen concentrations, significant numbers of eosinophils (731.3 +/- 232.9 x 10(3)/ml) were recruited only when the concentration of antigen used for segmental challenge was > or = 100-fold higher than the concentration needed to produce an 8 to 10 mm wheal 20 min after intradermal skin testing. In addition, large increases in bronchoalveolar lavage (BAL) albumin concentration (636.3 +/- 170.5 micrograms/ml) were observed only in this same group of subjects. The correlation coefficient between the logarithms of the BAL eosinophil concentration and albumin concentration was +0.82 (p < 0.001), and between eosinophil-derived neurotoxin and albumin it was +0.88 (p < 0.001). In a stepwise, multiple regression analysis, eosinophils accounted for 67% of the variance in BAL albumin concentration, whereas no other cell type was a significant predictor of albumin flux into BAL fluid. We conclude that eosinophil recruitment and degranulation are associated with large increases in bronchovascular permeability after segmental antigen challenge in humans. PMID- 8442606 TI - Differential in vitro regulation by glucocorticoids of monocyte-derived cytokine generation in glucocorticoid-resistant bronchial asthma. AB - We previously described a 3 kD neutrophil priming activity (NPA) derived from peripheral blood monocytes that is suppressed by glucocorticoid treatment of monocytes derived from individuals with corticosteroid-sensitive (CS) but not corticosteroid-resistant (CR) asthma. We compared the effects of glucocorticoids on the in vitro generation of other cytokines by monocytes of CS and CR asthmatic individuals. A total of 11 CS and 8 CR asthmatic subjects were studied. Monocytes were cultured overnight in the presence or absence of 5 micrograms/ml of lipopolysaccharide (LPS) with or without hydrocortisone (HC) or dexamethasone. TNF-alpha, IL-1 beta, and GM-CSF were measured by ELISA, mRNA for these cytokines were detected by northern analysis, and NPA was identified by its capacity to enhance ionophore-induced LTB4 generation from neutrophils. In the absence of LPS there was no significant difference in the generation of cytokines between monocytes derived from CS and CR individuals. Treatment of monocytes by 10(-6) M HC suppressed NPA generation from CS (72%, p = 0.002) but not CR subjects (10%, p = 0.47). In contrast there was no effect of glucocorticoids on the generation of other cytokines from monocytes of either CS or CR subjects. In the absence of LPS, mRNA for IL-1 beta and GM-CSF were not detected by northern analysis, and glucocorticoids had no significant effects on mRNA for TNF-alpha in either group. LPS at 5 micrograms/ml enhanced cytokine but not NPA generation and markedly increased cytokine mRNA in monocytes of both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8442607 TI - Airway mucosal inflammation even in patients with newly diagnosed asthma. AB - We have studied bronchial biopsies from 14 patients with newly diagnosed asthma (four men and 10 women), who had had asthma symptoms, on average, 7.4 months (range, 2 to 12 months) and from four control subjects. The patients had not received corticosteroids, disodium cromoglycate, or theophylline before the study. The bronchial biopsies were taken, using a rigid-tube bronchoscope under local anaesthesia, from two different airway levels: (1) inside the right upper lobe bronchus, and (2) at the opening of the right middle lobe. The specimens were prepared for both light and electron microscopy. The use of Slot grids 1 x 2 mm enabled a large area of the thin sections to be photographed and analyzed by applying a graphic Autocad program. There was an increase in the numbers of mast cells (p < 0.001), eosinophils (p < 0.05), lymphocytes (p < 0.05), and macrophages (p < 0.05) in the epithelium of patients with newly diagnosed asthma as compared with those in control subjects. In the lamina propria, these asthmatic patients had more eosinophils (p < 0.001), lymphocytes (p < 0.001), macrophages (p < 0.001), and plasma cells (p < 0.001) than did the control subjects. We conclude that, in asthma, an airway inflammatory process is present even at a clinically early stage of the disease. In the asthmatic airways, there are signs of a general inflammatory response caused by more than one cell type. PMID- 8442608 TI - Wheezing and airflow obstruction during methacholine challenge in children with cystic fibrosis and in normal children. AB - To study wheeze as an indicator of bronchial responses during standardized methacholine challenge (MCH), we used computerized analysis of respiratory sounds in children with cystic fibrosis (CF) and in healthy control subjects. We recorded tracheal and lung sounds from 10 young CF = yCF patients, mean age 5.7 yr (range 4 to 7 yr), 13 older CF = oCF, age 10.5 yr (8 to 18 yr), 7 young normal subjects = yNO, age 5.3 yr (4 to 7 yr), and 11 older normal subjects = oNO, age 11 yr (8 to 16 yr). Spirometry was obtained after each doubling concentration of methacholine until the concentration provoking a > or = 20% fall in FEV1 (PC20) or the end point (8 mg/ml) was reached. Sound and calibrated flow signals were recorded on tape and later analyzed by respirosonography. The concentration of methacholine associated with wheeze (PCw) was noted. Wheezing was quantified by its duration during inspiration (Tw/TI) and expiration (TW/TE). We found a positive response to MCH in 11 of 13 oCF (PC20 0.75 mg/ml, range 0.08 to 3.0) and in 3 of 11 oNO (PC20 4.2 mg/ml, range 2.5 to 6.5). Wheezing occurred in 6 oCF (PC20 < 8 mg/ml). In 7 yCF PC20 or PCW developed (1.51 mg/ml, range 0.125 to 4.0) versus 4 yNO (4.0 mg/ml, range 2.0 to 8.0). In 10 oCF subjects who performed MCH on three occasions within a 2-wk period, both positive and negative wheeze responses were reproducible. Patients who wheezed had a lower FRC compared with patients who did not (109 versus 147% of predicted, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8442609 TI - Elevated levels of lung surfactant protein A in sera from patients with idiopathic pulmonary fibrosis and pulmonary alveolar proteinosis. AB - An enzyme-linked immunosorbent assay using monoclonal antibodies to human lung surfactant protein A (SP-A) was applied to sera from patients with lung diseases. We examined whether SP-A appears in the sera of patients with diseases that are known to cause alterations in surfactant composition in bronchoalveolar lavage fluids, and we characterized the SP-A that was found. The level of SP-A in sera from 57 healthy volunteers was 45 +/- 3 ng/ml (mean +/- SEM). The levels in patients with idiopathic pulmonary fibrosis (IPF) (205 +/- 23 ng/ml, n = 32) and pulmonary alveolar proteinosis (PAP) (285 +/- 23 ng/ml, n = 6) were significantly higher than those in healthy control subjects (p < 0.01), whereas those of sarcoidosis (n = 16), pneumonia (n = 14), and tuberculosis (n = 14) were 52 +/- 27 ng/ml, 65 +/- 11 ng/ml, and 49 +/- 23 ng/ml, respectively. Electrophoresis and immunoblotting analysis demonstrated that the fraction isolated from serum of a patient with PAP or IPF by anti-SP-A immunoaffinity column chromatography consisted chiefly of human IgG and IgM, and that it also contained SP-A. Furthermore, IgG was found in preparation of purified human SP-A. SP-A was demonstrated to bind to nonimmune IgG coated onto microtiter wells. Gel filtration analysis revealed that serum SP-A was eluted at fractions of larger molecular size than was the purified SP-A. These findings suggest that SP-A appears in the bloodstream as a complex with immunoglobulin in IPF and in PAP. PMID- 8442610 TI - Theophylline in oral mucosal transudate. A practical method for monitoring outpatient therapy. AB - We tested the utility of a novel collection system that allows measurement of theophylline in oral mucosal transudate (OMT) to calculate serum theophylline concentrations. In 25 adult patients, theophylline levels in OMT correlated better than expectorated saliva with serum theophylline (r = 0.927 for OMT versus r = 0.831 for expectorated saliva, each p < 0.0001). In a subsequent study of 128 patients (118 adults and 10 children aged 4 to 12 yr), OMT and serum theophylline were measured and polynomial regression analysis performed to allow calculation of serum level for any given OMT level. Theophylline levels calculated from OMT values closely followed measured serum theophylline in two normal subjects after administration of either intravenous or oral theophylline. OMT samples collected by 24 patients at home were mailed to the laboratory for testing. Theophylline values from the home collection samples correlated closely (r = 0.930, p < 0.0001) with serum theophylline levels obtained at the same dose of theophylline. These findings suggest that once the relationship of serum to OMT theophylline is established in a given laboratory, the latter can be used to monitor outpatient theophylline therapy in adults (and possibly children) at times of the day otherwise inaccessible to serum sampling. PMID- 8442612 TI - Ozone-enhanced pulmonary infection with Streptococcus zooepidemicus in mice. The role of alveolar macrophage function and capsular virulence factors. AB - Ozone exposure has been shown to increase the susceptibility of mice to pulmonary bacterial infection. We report here the differences in susceptibility of two strains of mice (C3H/HeJ and C57Bl/6) to pulmonary challenge with Streptococcus zooepidemicus, and demonstrate an association between O3 exposure, reduced alveolar macrophage (AM) function, and increased mortality to infection. After a 3-h exposure to air or to 0.4 or 0.8 ppm O3, mice received an infection of bacteria by aerosol. Subsequent mortality observed over a 20-day period for any given exposure concentration was greater in the C3H/HeJ mice than in the C57Bl/6 mice. Phagocytosis assays identified the AM from O3-exposed lungs as having an impaired ability to engulf the bacteria. Baseline phagocytic activity in C3H/HeJ mice was lower than that in C57Bl/6 mice. Microbiologic assessment of the lungs at various times after infection revealed that the streptococci proliferated rapidly in the lungs of O3-exposed mice, grew more quickly upon isolation, and displayed a mucoid colony appearance indicative of increased encapsulation. In vitro assays confirmed that the encapsulated isolates prevented binding of the bacteria to AM, and reinfection of nonexposed mice with the encapsulated isolate resulted in increased mortality compared with infection with similar numbers of the original unencapsulated bacteria. We have demonstrated that O3 inhalation impairs AM activity in the lung. The streptococci are then able to proliferate and more fully express virulence factors, in particular, the antiphagocytic capsule, which prohibits the ingestion of bacteria by pulmonary phagocytes and leads to increased severity of infection. PMID- 8442611 TI - Respiratory muscle limitation in patients after pneumonectomy. AB - Exercise capacity is significantly impaired in postpneumonectomy patients who have relatively normal remaining lungs. Our objectives are to determine (1) the nature and extent of mechanical ventilatory abnormalities and oxygen cost of breathing in such patients, and (2) the efficacy of a selective respiratory muscle training program in improving ventilatory and exercise performance. A group of eight postpneumonectomy and eight normal subjects (mean ages 59 and 50 yr, respectively) were studied during steady-state exercise and resting voluntary hyperventilation. Ventilation, work of breathing, cardiac output, and oxygen costs of breathing were determined. Four postpneumonectomy and five normal subjects were studied before and after a respiratory muscle training program. In patients after pneumonectomy compared with normal control subjects, maximal oxygen uptake (VO2) was 56% lower (p < 0.001). Work of breathing was significantly higher at a given ventilation. Mechanical efficiency of ventilation was lower by 44% (p < 0.05). Near maximal VO2, 48% of any additional increment of total-body VO2 was required to sustain the associated increment in ventilatory work, compared with 28% in normal subjects (p < 0.05), suggesting that competition between respiratory and nonrespiratory muscles for oxygen delivery is a significant factor limiting exercise after pneumonectomy. After respiratory muscle training, maximal respiratory pressures improved but maximal sustained ventilation and maximal VO2 did not improve significantly, suggesting that selective respiratory muscle training is of limited utility in postpneumonectomy patients. PMID- 8442613 TI - Lactate breakpoint during slowly increasing work rates and irregular breathing. AB - The breakpoint (BP) in lactate (La) was determined using the noninvasive V-slope and VE/VO2 methods. Eight normal male subjects performed three maximal graded exercise tests (GXT) with 3-min work stages during normal breathing (NB) and during irregular breathing with hypoventilation (IB-HV). The IB-HV resulted in mild but significantly increased arterialized-venous PCO2, PETCO2 and irregular VE/VO2 and irregular breathing frequency. The correlation coefficients for linear regressions of the La BP with the V-slope and VE/VO2 BPs during NB were: 0.77 (p < 0.05) and 0.79 (p < 0.05), respectively, and during IB-HV the correlations coefficients were: 0.82 (p < 0.05) and -0.02 (p > 0.05) for V-slope and VE/VO2 BPs, respectively. The differences were more apparent from the regression coefficients with the La BP; the slopes with NB for V-slope and VE/VO2 BPs were 1.06 +/- 0.40 SEM and 1.38 +/- 0.43; the intercepts with NB were -0.22 +/- 0.24 and -0.67 +/- 0.33, respectively. During IB-HV the slopes for the V-slope and VE/VO2 were 1.02 +/- 0.29 and -0.02 +/- 0.47, and the intercepts were -0.11 +/- 0.40 and 1.57 +/- 0.64, respectively. The VE/VO2 slope and intercept with IB-HV were notably different. It was concluded that the V-slope and VE/VO2 methods determine the La BP with 3-min stages during NB, whereas only the V-slope method determined the La BP with IB-HV. PMID- 8442614 TI - Comparison of diaphragm EMG centroid frequencies: esophageal versus chest surface leads. AB - Previous work has suggested that diaphragm EMGs recorded from the lower thoracic wall yield spuriously low centroid frequencies (Fc). For this reason we compared EMGs recorded from two anterolateral thoracic wall locations with EMGs recorded simultaneously from a bipolar esophageal electrode in 11 stable quadriplegic patients. Their maximal inspiratory pressures (Pdimax) ranged from 31 to 85, averaging 55 cm H2O. Quadriplegic patients were selected to exclude EMG contamination of surface recordings by intercostal muscle activity. Recordings were made during resting breathing, voluntary hyperventilation, CO2-stimulated hyperventilation, and inspiratory resistance breathing at 50% of Pdimax. Centroid frequencies were consistently lower from surface recordings than from esophageal recordings. Centroid frequencies (Hz) recorded from the esophagus were 86.9 +/- 3.0 (SEM) resting, 93.4 +/- 3.7 during voluntary hyperventilation, 85.8 +/- 4.2 during CO2-stimulated ventilation, and 88.5 +/- 1.4 during inspiratory resistance breathing. Corresponding Fc values from simultaneous thoracic surface recordings were 62.6 +/- 3.6, 62.0 +/- 2.8, 58.6 +/- 3.1, and 58.8 +/- 2.5. On several subjects, decreases in Fc that occurred during sustained maximal inspiratory efforts were present in esophageal recordings but not in surface recordings. We conclude that thoracic surface recordings of the diaphragmatic EMG do not accurately reflect frequency information. PMID- 8442615 TI - Timing of tracheotomy in mechanically ventilated patients. PMID- 8442616 TI - Lung transplantation. Report of the ATS workshop on lung transplantation. American Thoracic Society, Medical Section of the American Lung Association. PMID- 8442617 TI - Search for mycobacterial DNA in granulomatous tissues from patients with sarcoidosis using the polymerase chain reaction. PMID- 8442618 TI - Endogenous sensory neuropeptide release enhances nonspecific airway responsiveness in guinea pigs. PMID- 8442619 TI - Decreased high-density lipoprotein cholesterol and increased low-density cholesterol levels in patients with colorectal adenomas. AB - OBJECTIVE: To study the relation between serum lipoprotein levels and the frequency of colorectal adenomas, the benign precursors of colorectal cancer. DESIGN: Cross-sectional. SETTING: University hospital in Germany. PATIENTS: The study included 822 of 1124 consecutive patients who underwent colonoscopy at our institution (302 patients were excluded because of malignant disease, chronic inflammatory bowel disease, familial polyposis, partial colectomy, or other chronic diseases). Of the 822 study patients, 194 had colorectal adenoma. MEASUREMENTS: Serum cholesterol fractions (high-density lipoprotein [HDL], low density lipoprotein [LDL], and very low-density lipoprotein [VLDL]) and presence or absence of adenomas; univariate and logistic regression analyses were carried out to evaluate the association between serum HDL, LDL, and VLDL cholesterol levels and the frequency of colorectal adenoma. RESULTS: Univariate analysis of the total patient group showed that the HDL cholesterol level was inversely related to the frequency of colorectal adenoma (odds ratio, 0.36; 95% Cl, 0.21 to 0.62) and that LDL and VLDL cholesterol levels were positively associated with adenoma frequency (odds ratio, 2.31 [Cl, 1.36 to 3.92] and 1.72 [Cl, 1.03 to 2.86], respectively). Univariate analysis of the subgroup of 89 patients with high-risk adenomas showed an inverse association between such adenomas and HDL cholesterol (odds ratio, 0.37; Cl, 0.18 to 0.76). A logistic regression analysis that included age and body mass index showed an association between lipoprotein levels and the presence of adenomas. The relative strength (in descending order) of these associations was as follows: HDL, LDL, VLDL, and total serum cholesterol. A logistic regression analysis of patients with high-risk adenoma showed a significant association between such adenomas and the HDL cholesterol level. CONCLUSIONS: Patients with colorectal adenomas have lower HDL cholesterol levels and higher LDL and VLDL cholesterol levels; these lipoproteins may have prognostic significance for the development of colorectal adenomas. PMID- 8442620 TI - Fluconazole prophylaxis of fungal infections in patients with acute leukemia. Results of a randomized placebo-controlled, double-blind, multicenter trial. AB - OBJECTIVE: To evaluate the efficacy and safety of fluconazole for prevention of fungal infections. DESIGN: A randomized, placebo-controlled, double-blind, multicenter trial. PATIENTS: Adults (257) undergoing chemotherapy for acute leukemia. INTERVENTION: Patients were randomly assigned to receive either fluconazole (400 mg orally once daily or 200 mg intravenously every 12 hours) or placebo. The study drug was started at initiation of chemotherapy and continued until recovery of neutrophil count, development of proven or suspected invasive fungal infection, or the occurrence of a drug-related toxicity. MEASUREMENTS: Fungal colonization, proven superficial or invasive fungal infection, empiric antifungal therapy with amphotericin B, drug-related side effects, and mortality. MAIN RESULTS: Fluconazole decreased fungal colonization (83 of 122 [68%] placebo patients compared with 34 of 119 [29%] fluconazole patients colonized at end of prophylaxis, P < 0.001) and proven fungal infections (27 of 132 [21%] placebo patients compared with 11 of 123 [9%] fluconazole patients infected, P = 0.02). Superficial fungal infections occurred in 20 of 132 (15%) placebo patients but in only 7 of 123 (6%) fluconazole patients (P = 0.01), whereas invasive fungal infections developed in 10 of 132 (8%) placebo patients and in 5 of 123 (4%) fluconazole patients (P = 0.3). Fluconazole was especially effective in eliminating colonization and infection by Candida species other than Candida krusei (66 of 122 [64%] placebo patients colonized at end of prophylaxis compared with 11 of 119 [9%] fluconazole patients, P < 0.001; 22 of 132 [17%] placebo patients infected compared with 7 of 123 [6%] fluconazole patients, P = 0.005). Aspergillus infections were infrequent in both fluconazole (3 cases) and placebo groups (3 cases). The use of amphotericin B, the incidence of drug-related side effects, and overall mortality were similar in both study groups. CONCLUSION: Prophylactic fluconazole prevents colonization and superficial infections by Candida species other than Candida krusei in patients undergoing chemotherapy for acute leukemia and is well tolerated. Fluconazole could not be clearly shown to be effective for preventing invasive fungal infections, reducing the use of amphotericin B, or decreasing the number of deaths. PMID- 8442621 TI - The incidence of perioperative myocardial infarction in men undergoing noncardiac surgery. AB - OBJECTIVES: To determine the incidence of and risk factors for perioperative myocardial infarction with noncardiac surgery and to test the accuracy of a risk stratification system. DESIGN: Prospective cohort study. SETTING: A large urban Veterans Affairs hospital. PARTICIPANTS: A total of 1487 men older than 40 years undergoing major, nonemergent, noncardiac operations. MEASUREMENTS: Infarction was established by at least two of the following: development of new Q waves, typical change in creatine kinase MB, and positive technetium pyrophosphate scintigraphy. Patients were stratified preoperatively into high-, intermediate-, low-, and negligible-risk strata based on clinical markers corresponding to different levels of coronary artery disease prevalence. MAIN RESULTS: Patients with coronary disease (high-risk stratum) had a 4.1% incidence of infarction (13 of 319; 95% CI, 1.8% to 6.4%); patients with peripheral vascular disease but no evidence of coronary disease (intermediate-risk stratum) had a 0.8% incidence (2 of 260, upper bound of CI, 2.0%); patients with high atherogenic risk factor profiles but no clinical atherosclerosis (low-risk stratum) had a 0% incidence (0 of 256, upper bound of CI, 1.2%). No cardiac deaths occurred in 652 men who had no atherosclerosis and low atherogenic risk factor profiles (the negligible-risk stratum). Factors independently associated with infarction included age more than 75 years (adjusted odds ratio, 4.77; CI, 1.17 to 19.41), signs of heart failure on the preoperative examination (adjusted odds ratio, 3.31; CI, 0.96 to 11.38), coronary disease (adjusted odds ratio, 10.39; CI, 2.27 to 47.46), and a planned vascular operation (adjusted odds ratio, 3.72; CI, 1.12 to 12.37). CONCLUSIONS: Coronary artery disease is the major risk factor for perioperative infarction. The stratification scheme identifies subsets of patients with different risks, and finer within-stratum distinctions can be made using additional variables. PMID- 8442622 TI - Nurse-assisted counseling for smokers in primary care. AB - OBJECTIVE: Physician-delivered advice to stop smoking is effective, but time demands often reduce the number of smokers who receive assistance. We evaluated three nurse-assisted interventions designed to minimize physician burden and increase counseling in primary care settings. DESIGN: Randomized controlled trial with a 12-month follow-up. SETTING: Internal medicine and family practice offices in a health maintenance organization. PARTICIPANTS: Smokers (n = 3161) who were patients of participating physicians or other medical care providers (n = 60). INTERVENTION: Medical care providers delivered a 30-second stop-smoking prompt to 2707 smokers and referred them to an on-site nurse smoking counselor. The nurse randomly provided a two-page pamphlet (advice control) or one of three nurse assisted interventions: 1) self-quit training; 2) referral to a group cessation program; or 3) a combination of self-quit training and referral. Each nurse delivered intervention included a 10-minute video, written materials, and a follow-up phone call. RESULTS: Physicians delivered brief advice to 86% of identified smokers during the 1-year program. The proportion of participants reporting abstinence after both 3 and 12 months of follow-up nearly doubled (P = 0.01) for the nurse-assisted self-quit (7.1%), group-referral (7.6%), and combination (6.9%) interventions, compared to brief physician advice alone (3.9%) (P < 0.05). Saliva cotinine tests confirmed these effects (P < 0.004), although quit rates were lower (3.4%, 4.7%, 4.3%, and 2.3%, respectively) because roughly one half of quitters chose not to provide a saliva sample and were counted as smokers. CONCLUSION: Involving nurses in counseling smokers reduces physician burden, makes counseling more likely, and significantly increases cessation rates compared with brief physician advice alone. PMID- 8442623 TI - Maltose-induced hyponatremia. PMID- 8442624 TI - Drug-induced disorders of glucose tolerance. AB - PURPOSE: To review the medications that influence glucose metabolism and to examine the mechanisms of these medications on glucose metabolism. DATA SOURCES: Data were obtained from a MEDLINE search back to 1966 and included animal and human studies published in the English language. STUDY SELECTION: Approximately 80% of original publications were included after review by the authors. Case reports were included if they provided additional information. DATE EXTRACTION: The original data from the literature were included on the basis of independent extraction by the authors. DATA SYNTHESIS: Many common therapeutic agents influence glucose metabolism. Multiple mechanisms of action on glucose metabolism exist through pancreatic, hepatic, and peripheral effects. Based on circumstances at the time of use, a drug may cause both hyper- and hypoglycemia in a patient. The patient's previous pancreatic reserve, nutritional state, use of other medication, or exposure to alcohol may influence the direction of the plasma glucose alterations. CONCLUSION: Hyperinsulinemia and insulin resistance form an intrinsic component of diabetes, hyperlipidemia, and atherosclerotic vascular disease (syndrome X). The induction of hyperinsulinemia and insulin resistance by medication may therefore counteract intended benefits. An extensive review of recent medication in patients with disorders of glucose tolerance and the avoidance of polypharmacy are recommended. It is prudent to monitor plasma glucose values when it is not possible to avoid prescription of medication with known effects on carbohydrate metabolism. PMID- 8442625 TI - Evaluating the care of general medicine inpatients: how good is implicit review? AB - OBJECTIVE: Peer review often consists of implicit evaluations by physician reviewers of the quality and appropriateness of care. This study evaluated the ability of implicit review to measure reliably various aspects of care on a general medicine inpatient service. DESIGN: Retrospective review of patients' charts, using structured implicit review, of a stratified random sample of consecutive admissions to a general medicine ward. SETTING: A university teaching hospital. PATIENTS: Twelve internists were trained in structured implicit review and reviewed 675 patient admissions (with 20% duplicate reviews for a total of 846 reviews). RESULTS: Although inter-rater reliabilities for assessments of overall quality of care and preventable deaths (kappa = 0.5) were adequate for aggregate comparisons (for example, comparing mean ratings on two hospital wards), they were inadequate for reliable evaluations of single patients using one or two reviewers. Reviewers' agreement about most focused quality problems (for example, timeliness of diagnostic evaluation and clinical readiness at time of discharge) and about the appropriateness of hospital ancillary resource use was poor (kappa < or = 0.2). For most focused implicit measures, bias due to specific reviewers who were systematically more harsh or lenient (particularly for evaluation of resource-use appropriateness) accounted for much of the variation in reviewers' assessments, but this was not a substantial problem for the measure of overall quality. Reviewers rarely reported being unable to evaluate the quality of care because of deficiencies in documentation in the patient's chart. CONCLUSION: For assessment of overall quality and preventable deaths of general medicine inpatients, implicit review by peers had moderate degrees of reliability, but for most other specific aspects of care, physician reviewers could not agree. Implicit review was particularly unreliable at evaluating the appropriateness of hospital resource use and the patient's readiness for discharge, two areas where this type of review is often used. PMID- 8442626 TI - Resistance to antimicrobial drugs--a worldwide calamity. AB - The introduction of penicillin 50 years ago was followed by an extraordinary period of discovery, exuberant use, and predictable obsolescence. Resistant bacterial strains have emerged and have spread throughout the world because of the remarkable genetic plasticity of the microorganisms, heavy selective pressures of use, and the mobility of the world population. New and more expensive drugs have appeared almost in the nick of time, but it is doubtful that they will keep pace. The problem of resistance to antimicrobial drugs is particularly troublesome in developing countries. The underlying problems are largely economic and societal, and no ready solutions are available. An urgent need exists for more appropriate selection and use of antimicrobial drugs in the developed as well as in developing countries. The focus in developing countries should be on the availability of safe and effective drugs and on the enforcement of more responsible national drug policies. These issues must be addressed by the collective action of governments, the pharmaceutical industry, health care providers, and consumers. The developed countries have an important stake in the ways in which antibiotics are used in developing countries because resistant microorganisms do not recognize national boundaries. PMID- 8442627 TI - Lethal cascade. PMID- 8442628 TI - Clinical peer review: burnishing a tarnished icon. PMID- 8442629 TI - Coronary heart failure and left ventricular diastolic dysfunction. PMID- 8442630 TI - Prolonged weakness and vecuronium. PMID- 8442631 TI - Immunosuppressive effect of zidovudine. PMID- 8442632 TI - Immunosuppressive effect of zidovudine. PMID- 8442633 TI - Significance of Streptococcus bovis endocarditis. PMID- 8442634 TI - Bacteria on the common communion cup. PMID- 8442635 TI - Offering advance directives. PMID- 8442636 TI - Offering advance directives. PMID- 8442637 TI - Offering advance directives. PMID- 8442638 TI - Making the blood supply safer. PMID- 8442639 TI - Pathologists are doctors. PMID- 8442640 TI - [Development, equilibrium and role of microbial flora in the newborn]. AB - Development of the digestive tract intestinal flora is the result of a specific selection process to which the multiple maternal or environmental bacteria that penetrate into the neonatal gut are subjected. In breast-fed infants, Escherichia coli and streptococci are the first bacteria to appear in the gut. They are usually, but not always, followed by a population of Bifidobacterium which quickly becomes predominant. In bottle-fed infants, the intestinal flora is more variable and often includes, in addition to the organisms mentioned above, other enterobacteria and a wider range of obligate anaerobes. Studies of experimental models have shown that the nature of milk fed to the offspring and even the lactating mother's diet have substantial effects on the sequence of development of the neonatal intestinal flora. A large number of factors capable of inhibiting or permitting in vitro growth of various bacterial species have been identified in milk. However, no in vitro activity of these factors added to milk has ever been demonstrated. These factors include "bifidus factors", which promotes the growth of Bifidobacterium, and lactoferrin and immunoglobulins, which prevent colonisation of the gut by pathogenic enterobacteria. Immune factors in milk play a key role in interactions between the microbial flora and gut mucosa. However, they seem to have no effect on the growth of bacterial populations in the gut lumen. A number of pioneer bacteria, which are the first to arrive in the gut, are capable of effectively blocking growth of other bacteria introduced later in the ecosystem. In some instances, these pioneer bacteria also inhibit production of toxins by pathogenic species. Consequently, it is important to adhere to the recommended gradual changes in diet which allow these species to sequentially colonize the gut. PMID- 8442641 TI - [Ischemic cerebrovascular accidents in homozygous sickle cell anemia. Two case reports]. AB - Two cases of ischemic stroke in children of Tunisian descent with sickle cell anemia are reported. Patients were aged 3 years and 14 years, respectively. Periodic partial exchange transfusions with sedimented red blood cells of identical phenotype prevented further episodes of ischemic stroke. Transplantation of HLA-identical bone marrow from a family member offers a chance of complete cure of the hemoglobin disorder in these children who are at risk of recurrent stroke. PMID- 8442642 TI - [Severe megaloblastic anemia in child breast fed by a vegetarian mother]. AB - The case of a 15-month-old, strictly breast-fed infant whose mother had been following a vegetarian diet for ten years is reported. The infant had severe megaloblastic anemia with an arrest in growth, hypotonia, and failure of psychomotor development. The very low levels of vitamin B12 in the infant's serum and mother's milk confirmed the diagnosis. Management of such cases consists in administration of vitamin B12 supplements, with a blood transfusion if needed. Other concomitant deficiencies should be looked for. The outcome is rapidly favorable. The patient reported here is now four years of age and has normal statural growth and psychomotor development. PMID- 8442643 TI - [Hypoglycemia provoked by clandestine injections of insulin in the diabetic child]. AB - The treatment of insulin-dependent diabetes mellitus in a child generates new constraints in the family and requires adjustments of the daily routine. Refusal of these changes may lead to poor compliance with the treatment regimen. Poor or mistaken daily results and repeated episodes of ketoacidosis may occur as a result. Clandestine injection of insulin responsible for apparently inexplicable episodes of hypoglycemia is less common. Three new cases are reported herein. Clinical diagnosis is fairly easy and biological findings can provide confirmation. Acknowledgement of the injections by the patient is important in order to gain insight into his or her motives. Depression is known to be common among diabetics and the injections may be a symptom of depression. Another possibility is that the child expects to achieve an "irrational recovery" from the disease by taking control over the treatment. Furthermore, a child with access to a highly active drug like insulin can use this situation to acquire and maintain exceptional status within the family. The diagnosis of factitious hypoglycemia requires in every case an in-depth evaluation which may lead to psychotherapy for the child or for the entire family. PMID- 8442644 TI - [Multicystic encephalomalacia in a surviving twin after death of the other twin in utero]. AB - A case of multicystic encephalomalacia in a twin is reported. The other twin died in utero at 32 weeks gestational age. Because there was no evidence of fetal distress the pregnancy was allowed to continue until 36 weeks gestational age. Injuries to the surviving twin due to disseminated intravascular coagulation (DIVC) and vascular thrombosis or to anoxia and ischemia may occur when there are anastomoses between the circulatory systems of the two twins, i.e., in monochorionic pregnancies. The classically recommended strategy is to wait for adequate maturity of the surviving fetus (36 weeks). It is suggested that this attitude may be overly expectant and may deserve reappraisal. PMID- 8442645 TI - [Excessive water intake with intoxication as a manifestation of anorexia nervosa]. AB - A case of anorexia nervosa revealed by water intoxication with severe hyponatremia is reported after a search of the literature demonstrated the rarity of such cases. Pathophysiological mechanisms involved are discussed. Hospitalization in a unit for adolescents in which pediatricians and psychiatrists work together allowed both prompt treatment of metabolic disorders and early management of anorexia nervosa, which is associated with improved prognosis. PMID- 8442646 TI - [HbC/beta-thalassemia association. Eleven cases observed in Tunisia]. AB - Eleven cases of simultaneous HbC hemoglobinopathy and beta-thalassemia were detected during a study of 11,200 subjects at high risk for inherited hemoglobin anomalies. In seven cases, main clinical manifestations were anemia and enlargement of the spleen, whereas the four other patients were apparently free of symptoms and were diagnosed during routine tests in family members of affected patients. Microcytosis and hypochromia were found in every case. Most of the patients were from the North-Western part of Tunisia. Blood transfusions were required in only one patient, who was an infant with HbC/beta + thalassemia. PMID- 8442647 TI - [Acquired giant lobar emphysema in an artificially ventilated premature infant. Cured by corticosteroid therapy]. AB - A case of acquired giant lobar emphysema in a premature triplet born at 31 weeks gestational age and treated by artificial ventilation is reported. Corticosteroid therapy was remarkably successful. PMID- 8442648 TI - [A prospective study of mycoplasma infection in a neonatal unit]. AB - Ureaplasma urealyticum and Mycoplasma hominis were recovered from nasopharyngeal aspirates from 25% of 63 infants admitted to a neonatal unit; this proportion is significantly higher than that seen in a control population of maternity ward babies (0%). Birth by cesarean section was associated with a reduced risk of recovery of mycoplasmas. No specific diseases were significantly associated with recovery of mycoplasmas; furthermore, no obstetrical factors were associated with recovery of mycoplasmas from the neonates and no association was found between mycoplasma infection and respiratory distress. However, fetal distress, probably of multifactorial origin, was found in 44% of neonates with positive cultures for Ureaplasma urealyticum; this proportion was significantly elevated as compared with the subgroup of infants negative for U. urealyticum, suggesting that fetal distress may increase the infectivity of this opportunistic organism. PMID- 8442649 TI - [The risk of extra-colonic extension in Crohn's colitis]. AB - One hundred and two patients with Crohn's colitis present on average for 8 years, were studied retrospectively in order to determine whether or not a group of patients existed in whom the disease remained limited to the colon, and if such a group could be identified early on in the course of the disorder. At the time of the diagnosis of Crohn's disease, 34 patients had a concomitant anoperineal lesion, while 68 had disease affecting the colon only. In the latter, at the end of the follow-up period, the disease remained exclusively limited to the colon in 39 cases (57 p. cent). The actuarial rate of non-extra-colonic spread was 75, 40 and 35 p. cent at 5, 10 and 15 years respectively. Spread involved above all the anoperineal region (55 p. cent at 10 years), and less often the ileum (20 p. cent at 10 years). In patients monitored for at least 6 years, there was no significant difference between those in whom disease had spread and those in whom it remained limited to the colon, regarding the main initial clinical findings by history and examination, the same applying after the disease had been present for 3 years. These results would go against the existence of a specific entity of "Crohn's disease affecting the colon as an organ" and support the opinion that coloproctectomy with a pouch should be avoided in colitis due to Crohn's disease. PMID- 8442651 TI - [Difficult-to-diagnose organisms responsible for diarrhea in the immunocompetent patient]. AB - In cases of diarrhea, the two chief difficulties which the clinician must deal with are ability to demonstrate the nature of the pathogenic agent and, secondly, to be able to incriminate an organism found by stool culture as being pathogenic. The periodic emission of the parasite in coccidial infestations and in giardia infections requires repeated stool examinations. However, the persistence of a negative stool culture should lead to a search for a systemic cause such as malaria, a bacterial infection or toxin. Once an organism is identified, the distinction between a merely saprophytic nature and actual pathogenicity in the case of many parasites or candida can be determined on the basis of the clinical context and the underlying status of the patient. The epidemic context must also be taken into account, a healthy carrier state representing a fecal threat to other high risk patients, in particular regarding ameba and blastocyst infestations. PMID- 8442650 TI - [Can antibiotic-associated diarrhea be prevented?]. AB - Post-antibiotic diarrhea is common but rarely serious. The chief cause is changes in the normal intestinal flora. Decrease in the number of bacteria leads to maldigestion of carbohydrates, resulting in osmotic diarrhea. Disappearance of the flora encourages the emergence of resistant strains, e.g. Clostridium difficile. General measures concern the prescription of antibiotics and the use of probiotics. The latter restore and replace the normal flora and prevent more than half of all cases of diarrhea, in particular serious forms and pseudo membranous colitis. Antibiotics are not accompanied by any complication in 80% of instances. Probiotics should be used in high risk patients: elderly, seriously ill or hospitalised for long periods. PMID- 8442652 TI - [Hepatitis due to ticlopidine: a new case]. PMID- 8442653 TI - [The importance of hypergastrinemia in the diagnosis of Biermer's disease in the adult]. AB - Achlorhydria that is due to antrum sparring atrophic gastritis is a characteristic finding in pernicious anemia. As a consequence of this achlorhydria serum gastrin level rise. Usually several signs are required for assessing a pernicious anemia: megaloblastic anemia, low serum cobalamin level, positivity of a Schilling test, low level of intrinsic factor in the gastric juice, existence of anti-intrinsic factor antibodies in plasma and/or in gastric juice. In this study the usefulness of the serum gastrin level is assessed. We report here the results in investigating sixteen patients with a pernicious anemia. All had: megaloblastic changes on bone marrow examination, serum cobalamin level lower than 150 pg/ml. For 14 patients the performed Schilling test was positive. For 2, no Schilling test was done, but anti-intrinsic factor antibodies were elevated. Serum gastrin levels were higher than 150 pg/ml (254 to 1770 pg/ml). In our patients with pernicious anemia, as a result of hypo or achlorhydria, serum gastrin increase was higher than in any other cause of hypochlorhydria: anti-acid treatment, vagotomy ... Measurement of serum gastrin is easy. High levels are simple to explain if found together with a sparing antrum atrophic gastritis and/or a low level of serum cobalamin. Serum gastrin measurement may be a cornerstone of rapid and reliable diagnosis of pernicious anemia. PMID- 8442654 TI - Influence of extracellular matrix overlay on phenobarbital-mediated induction of CYP2B1, 2B2, and 3A1 genes in primary adult rat hepatocyte culture. AB - To obtain efficient induction by phenobarbital (PB) of cytochrome P450 (CYP) genes in primary hepatocyte culture, previous studies have demonstrated the importance of culturing hepatocytes on a substratum derived from extracellular matrix (ECM or Matrigel), or in highly enriched medium formulations such as Chee's. In the present study, we have reexamined a variety of hepatocyte culture conditions and their relative abilities in preserving the PB-induction response within the CYP2B and 3A gene subfamilies. A modified culture system was developed that combines a highly effective medium formulation in conjunction with dilute concentrations of a Matrigel overlay. Specifically, hepatocytes were attached to a Collagen I substratum and overlaid with either daily (50 micrograms/ml medium) or single (233 micrograms/ml) additions of Matrigel. The PB-induction response obtained in vitro closely resembled that occurring in vivo. Induction in culture by 1 mM PB of CYP2B1, 2B2, and 3A1 mRNA levels was highly dependent on a variety of factors, including medium formulation and 0.1 microM dexamethasone addition. The response to dexamethasone addition on this gene battery varied in a medium specific manner. Cells maintained a higher level of PB-induction response when maintained in Williams' E medium than with Chee's, Waymouth's, or Ultraculture media. The kinetics of PB induction also were more rapid in cells cultured in Williams' E medium. PB exposures in Chee's medium resulted in elevation of two CYP2B-immunoreactive proteins as detected by Western blot analysis, together with increased rates of O-dealkylation of benzyloxy- and pentoxyresorufin. However, Chee's formulation produced an abnormal PB-induced expression of CYP1A1, as determined by mRNA analysis, high rates of O-dealkylation of 7-ethoxyresorufin, and inhibition of enzymatic activity by 1 microM alpha-naphthoflavone. This paradoxical expression of CYP1A1 was not observed in PB-treated cultures grown in Williams' E medium. Thus, these studies demonstrated that the use of a physiologically balanced medium, i.e., Williams' E formulation, together with an overlay of ECM, preserves PB-induction responsiveness closely resembling that observed in vivo, and should better facilitate mechanistic investigations into the molecular nature of PB induction. PMID- 8442655 TI - Establishment of a hydrogen peroxide resistant variant of renal tubular epithelial cells: role of calcium-independent phospholipase A2 in cell damage. AB - Renal epithelial cells resistant to oxidant stress mediated by hydrogen peroxide have been isolated and characterized. African green monkey kidney epithelial cell line, BSC-1 cells, chronically exposed to 50 microM hydrogen peroxide for 15 passages exhibited increased catalase (1.5-fold) and glutathione peroxidase (2.4 fold) activity, as well as increased total cellular glutathione (1.6-fold). This was associated with the acquisition of resistance to hydrogen peroxide cytotoxicity, as judged by nuclear staining with ethidium homodimer and clonogenic survival assay. H2O2-adapted and wild-type BSC-1 cells were used to examine the role of elevated cytosolic calcium concentration and the activation of phospholipase A2 in the development of lethal cell injury. Despite dramatic differences in resistance to oxidative stress, both cell types showed similar kinetics of cytosolic calcium increase in response to challenge with hydrogen peroxide. In contrast to this, oxidant-induced release of arachidonic acid correlated with the resistance of both types of BSC-1 cells to oxidative stress. A mechanism-based inhibitor of calcium-independent phospholipase A2 (Hazen et al., J. Biol. Chem. 266, 7227, 1991) reduced oxidant-induced lethal cell injury, suggesting that this class of phospholipases contributes to damage of BSC-1 cells exposed to hydrogen peroxide. H2O2-adapted BSC-1 cells may represent a valuable tool to study adaptation to oxidative stress and various mechanisms of cell injury. PMID- 8442656 TI - Purification and characterization of glutathione S-transferase of murine ovary and testis. AB - Recent studies have indicated that sex hormones may regulate expression of murine glutathione S-transferase (GST) isozymes. Therefore, we have purified and compared GST isozymes of murine ovary and testis, two tissues with markedly different hormonal milieu. Isoelectric profiles of the GST isozymes of both these tissues were found to be closely similar. Both expressed one alpha-class GST (pI9.8), one pi-class GST (pI8.9), and three mu-class GSTs (pI8.5, 7.9, and 6.7). In addition, an isozyme (pI5.8) corresponding to the rat GST 8-8 was also expressed in both these tissues. Total GST protein/g tissue was about 1.7-fold more abundant in testis. The specific activities of the cationic isozymes of testis were 1.2- to 2.4-fold higher as compared to those of ovaries. On the other hand, the specific activities of the anionic testicular isozymes were 6.4- to 10 fold higher compared to the corresponding ovarian isozymes. Structural properties including the N-terminal sequences of the testicular isozymes were indistinguishable from those of their ovarian counterparts. The N-terminal sequence of the pi-class GST of both tissues was similar to that of mouse liver GST pi. The three mu-class GSTs of testis and ovary arise from the dimeric combinations of two subunits whose N-terminal sequences determined up to 24 residues were similar to those of mouse liver GST subunits mu 1 and mu 2. Although testicular and ovarian isozymes were structurally similar, Kcat values of some of the testicular isozymes were up to 10-fold higher than those of the corresponding ovarian isozymes. The substrate specificities were also significantly different for the corresponding isozymes of testis and ovary. PMID- 8442657 TI - Inhibition of vascular permeability factor (vascular endothelial growth factor) with antipeptide antibodies. AB - Vascular permeability factor (VPF), also known as vascular endothelial cell growth factor (VEGF), is a 34- to 43-kDa dimeric protein synthesized and secreted by a variety of tumor and normal cells. At nanomolar concentrations, VPF causes an increase in microvascular permeability and is thought to be responsible for enhanced permeability of tumor blood vessels and for the fluid accumulation associated with solid and ascites tumors. In addition, VPF/VEGF is a mitogen for endothelial cells and may play an important role in maintaining vascular endothelium and in promoting tumor angiogenesis. Antibodies were raised against a series of synthetic peptides derived from the predicted human VPF amino acid sequence. The antibodies were assayed for their ability to bind native and denatured/reduced VPF. Antibodies to peptides from the N- and C-termini bound both denatured/reduced and native VPF; antibodies directed to internal segments (e.g., amino acids 27-48 and 85-101) strongly bound denatured/reduced VPF but were substantially less effective at binding native VPF. These results suggest that the N- and C-termini are exposed regions of the protein in solution. Individually, antibodies to the N- and C-termini each partially blocked VPF permeability activity, and, in combination, blocked nearly 100% of this activity. Also, the N- and C-terminal antibodies blocked the VPF-mediated stimulation of both endothelial cell growth and increase in free cytosolic calcium. PMID- 8442658 TI - Solubilization and characterization of atrial muscarinic acetylcholine receptors in sucrose monolaurate. AB - Muscarinic acetylcholine receptors (mAChRs) can be solubilized from porcine atrial membranes in sucrose monolaurate (SM-1200) with retention of up to 80% of N-[3H]methylscopolamine ([3H]NMS) binding activity. The mAChRs solubilized by SM 1200 were relatively stable at 4 degrees C with an estimated half-life (tau 1/2) of the ligand binding activity of 19 days. Inactivation of the ligand binding activity is dependent on the incubation temperature, and tau 1/2 was estimated to be 5.7 h at 20 degrees C, 28 min at 30 degrees C, and less than 1 min at 45 degrees C. The activation energy of the receptor inactivation was estimated to be 199 kJ/mol. Ligand binding characteristics of SM-1200-solubilized mAChRs were similar to those of digitonin/cholate-solubilized receptors. Sucrose density gradient centrifugation revealed a single peak with an apparent sedimentation coefficient of 5.7 S. The solubilized atrial mAChRs were purified approximately 1000-fold by using affinity chromatography with aminobenztropine as the ligand. The purified mAChRs were reconstituted with GTP binding regulatory proteins (G(o)) in lipid vesicles, and the reconstituted vesicles showed guanine nucleotide-sensitive, high-affinity agonist binding and agonist-stimulated GTP gamma S binding in the presence of GDP. Thus, sucrose monolaurate is a new detergent in which mAChRs can be solubilized in stable form with high yield and purified up to 1000 times with retention of the binding activity with muscarinic ligands and G-proteins. PMID- 8442659 TI - Sequential proton NMR resonance assignments, circular dichroism, and structural properties of a 50-residue substrate-binding peptide from DNA polymerase I. AB - Peptide I, a 50-amino acid synthetic peptide based on residues 728 to 777 of DNA polymerase I, binds dNTP substrates and duplex DNA (G. Mullen, P. Shenbagamurthi, and A.S. Mildvan, J. Biol. Chem. 264, 19637-19647, 1988). The structural properties of peptide I at pH 3.9 have been studied by CD spectroscopy and by 2D proton NMR at 600 MHz. The CD spectra are fit by assuming that peptide I contains 17% helix, 17% beta-structure, and 66% coil. The substrate dATP binds tightly to peptide I under these conditions (KD = 0.5 microM) as determined by fluorescence quenching but induces no change in peptide conformation, as detected by CD spectroscopy. Proton resonances of peptide I have been assigned by double quantum filtered correlated spectroscopy, total correlated spectroscopy, and nuclear Overhauser effect spectroscopy. As found with other peptides, peptide I is best characterized by both extended and partially folded secondary structures which equilibrate rapidly on the NMR time scale. A region from residues 3 through 10 displays nuclear Overhauser effects (NOEs) consistent with the rapid equilibration of a nascent helix with a random extended structure. Alternatively this segment of residues is consistent with a series of three opened-out turns. A nonclassical turn is found between residues 14 and 17 and from residues 44 to 47, the latter closing irregular antiparallel strands from residues 42 to 48. The remainder of the peptide is a coil. A residue-by-residue comparison of the best fit solution structure of the peptide with that of the corresponding sequence in the X-ray structure of the complete enzyme reveals that 36% of the amino acids are found to be in a conformation similar to that in the enzyme. Such partial and transient folding of the peptide indicates that the major role of the remainder of the protein is to provide structural support for the active site region of the enzyme. As detected by interresidue NOEs and NOEs to water protons, the homologous sequence Leu-37-Ile-38-Tyr-39-Gly-40, together with Phe-15 of the peptide, provides an exposed hydrophobic cluster of residues which may constitute the substrate binding site. An exposed cluster of cationic residues consisting of Arg-27, Arg-28, Lys-31, and possibly Arg-48 may provide the binding site for duplex DNA. PMID- 8442660 TI - Hydrogen peroxide-dependent formation and bleaching of the higher oxidation states of bovine erythrocyte green hemeprotein. AB - The ferric and ferrous forms of bovine erythrocyte green hemeprotein react with hydroperoxides to form higher oxidation state intermediates with absorbance maxima in the Soret region at 426 and 422 nm, respectively. In the absence of an appropriate reductant, these intermediates undergo rapid bleaching reactions. 2,2'-Azinobis(3-ethylbenzthiazoline-6-sulfonic acid) rapidly reduces the intermediate formed by reaction of ferric green hemeprotein with hydrogen peroxide, thereby preventing bleaching and allowing the rate of the intermediate formation to be calculated from the coupled dye oxidation. This rate constant of 70 M-1 s-1 at 23 degrees C is similar to those determined by bleaching and by direct photometric detection of the intermediate. Dihydroriboflavin rapidly reduces the intermediate formed by reaction of ferrous green hemeprotein with hydrogen peroxide, thereby preventing bleaching and allowing the rate of the intermediate formation to be calculated from the coupled dihydroriboflavin oxidation; the rate constant of 2 x 10(4) M-1 s-1 at 23 degrees C is similar to the value calculated by direct detection of the intermediate. The results demonstrate that, in contrast to the reductase activity of its heme-free form, the green heme form of the protein reacts with hydroperoxides to generate highly unstable peroxide complexes. PMID- 8442661 TI - Specificity of fucose transfer to GlcNAc residues of extended chain neolacto series glycolipids catalyzed by human alpha 1-->3fucosyltransferases: effect of the lipidic environment on the myeloid enzyme form. AB - Multiple alpha 1-->3fucosyltransferases occur in the human genome of which the Lewis (FucT-III), myeloid (FucT-IV), and plasma (FucT-V) enzyme forms have received the greatest attention. In this paper, the acceptor properties of the myeloid alpha 1-->3fucosyltransferase from human promyelocytic leukemia HL-60 cells have been studied. Fucose transfer into glycolipid acceptors was activated by detergents G-3634-A or taurodeoxycholate resulting in efficient transfer to neutral acceptors but poor transfer to sialylated acceptors, characteristic of the myeloid-type enzyme. Fucose transfer to nLc6 yielded both mono- and difucosyl derivatives under both detergent conditions. The nLc6 monofucosyl products were isolated and analyzed by TLC immunostaining and fast atom bombardment-mass spectroscopy analysis. The G-3634-A monofucosyl product was found to be composed solely of V3FucnLc6, whereas that with taurodeoxycholate was determined to be a mixture of III3FucnLc6 and V3FucnLc6 in near equal amounts. Analysis of reaction products using enzyme activation by phospholipids indicated that phosphatidylethanolamine and phosphatidylinositol behaved similarly to G-3634-A. In contrast, phosphatidylglycerol yielded results similar those of taurodeoxycholate. Fucose transfer to VI3NeuAcnLc6 yielded approximately 75% of the product as the III-GlcNAc monofucosyl derivative regardless of the detergent or phospholipid condition used. Analysis of fucose transfer to nLc6 catalyzed by the Lewis enzyme from Colo 205 cells using taurodeoxycholate yielded solely the III-GlcNAc monofucosyl derivative, whereas the predominant product with G-3634-A was V-GlcNAc fucosylated. In contrast, under both conditions only the V-GlcNAc monofucosylation product was found with the enzyme from NCI-H69 cells. The results indicate that subtle intrinsic differences exist between human alpha 1- >3fucosyltransferases. Modulation of enzyme specificity via the nature of the membrane environment could participate in regulation of expression of distinct cell surface antigens. PMID- 8442662 TI - Purification and characterization of an N-acetyllactosamine-specific lectin from larvae of a moth, Phalera flavescens. AB - A lectin (Phalera flavescens agglutinin, PFA) of a moth (P. flavescens) has been isolated from hemolymph by DEAE-Toyopearl followed by Cellulofine GCL-1000 chromatography. On size-exclusion chromatography, PFA showed a molecular mass of about 74 kDa, and on sodium dodecyl sulfate-polyacrylamide gel electrophoresis it was separated into two different subunits, glycosylated 18-kDa and unglycosylated 17-kDa subunits, suggesting that PFA occurs as a heterotetrameric protein. N Acetyllactosamine and laminin inhibited the hemagglutinating activity of PFA. Studies involving Synsorbs showed that PFA interacts with the Gal beta 1- >4GlcNAc group and that nonsubstituted hydroxyl groups at the C-2 and C-4 positions of the galactose residue were essential for interaction with PFA, whereas substitution at the C-3 position of the galactose did not inhibit the interaction between PFA and sugar chains associated with N-acetyllactosamine. PFA is not mitogenic for native or desialylated mouse thymocytes or splenocytes. PMID- 8442663 TI - N-acylphosphatidylethanolamine synthesis in plants: occurrence, molecular composition, and phospholipid origin. AB - We have identified a microsomal phospholipid as N-acylphosphatidylethanolamine (NAPE) that was radiolabeled following incubation of 1-day-old cotyledons of cotton seedlings with [14C]ethanolamine. Radiolabeled NAPE comigrated with commercially available L-alpha-dipalmitoyl phosphatidyl(N-palmitoyl)ethanolamine (std-NAPE) in one- and two-dimensional TLC. This NAPE comprised 7.2 +/- 1.0% (by weight) of microsomal phospholipids when hot isopropanol was used to inactivate endogenous phospholipases prior to extraction of lipids. In vitro degradation of putative cottonseed radiolabeled NAPE by Streptomyces chromofuscus phospholipase D resulted in production of a ninhydrin-reactive, radiolabeled lipid which comigrated with N-acylethanolamine (NAE) that was produced from a similar enzymatic cleavage of std-NAPE. Transmethylation of cottonseed radiolabeled NAE yielded radiolabeled ethanolamine and fatty acid methyl esters, nearly all of which were saturated (myristate, palmitate, and stearate together were 92% of the acyl components of cottonseed NAE). Positional analysis and relative abundance of the O-acyl groups of cottonseed microsomal NAPE were determined following a double enzymatic cleavage with Trimeresurus flavoviridis venom (phospholipase A2 activity) and S. chromofuscus phospholipase D. We substantiated our identification of cottonseed NAPE by 1H NMR spectroscopy and by mass spectrometry (fast-atom-bombardment ionization and tandem MS, FAB-MS/MS). Radiolabeled NAPE was synthesized in vivo in varying amounts from [14C]ethanolamine applied to maturing seeds of cotton and soybean, cotyledons of dark-grown cotton and soybean seedlings, cotyledons of light-grown okra, cotton and soybean seedlings, endosperm tissue of castor bean, and suspension cell cultures of rice. In pulse chase radiolabeling experiments in cotyledons of 1-day-old cotton seedlings, radiolabeled NAPE increased and radiolabeled phosphatidylethanolamine (PE) decreased over a 12-h chase period (in the dark or light), suggesting that NAPE was synthesized from PE in vivo. In vitro, the synthesis of NAPE from PE (radiolabeled in vivo) proceeded in a linear fashion in microsomes of cotton cotyledons with or without 1 mM EGTA and with or without 1 mM CaCl2 for 90 min. NAPE was synthesized in vitro from PE synthesized by the exchange pathway (microsomes preincubated with [14C]++e+thanolamine) and from PE synthesized by the nucleotide pathway (microsomes preincubated with [14C]CDPethanolamine). Collectively, our data indicate that (a) NAPE is a widespread, natural phospholipid component of plants, (b) NAPE is synthesized in vivo under normal physiological growth conditions in cotyledons of cotton seedlings, (c) NAPE is localized and synthesized in cottonseed microsomes, and (d) NAPE is likely synthesized by a direct acylation of PE. PMID- 8442664 TI - Effects of Cu-Zn superoxide dismutase overexpression of life span and resistance to oxidative stress in transgenic Drosophila melanogaster. AB - Reactive oxygen species have been postulated to be a causal factor in the aging process due to their ability to inflict molecular damage. The role of the enzyme copper-zinc superoxide dismutase (Cu-Zn SOD; superoxide:superoxide oxidoreductase; EC 1.15.1.1), which scavenges superoxide anion radicals, as a longevity determinant was examined in transgenic Drosophila melanogaster. A genomic fragment containing the Drosophila Cu-Zn SOD gene was introduced into the germ cells via a P element containing Casper vector. In different transgenic lines, overexpression of SOD by 32-42% above normal had either a minor and/or an insignificant effect on life span of the flies and their ability to withstand experimental oxidative stress, induced by paraquat intake and exposure to hyperoxia (100% oxygen). Transgenics showing a small increase in mean life span also exhibited a corresponding improvement in their resistance to hyperoxia but not paraquat. The maximum life span of populations was not affected. PMID- 8442665 TI - Peptide compositions of the cerebrovascular and senile plaque core amyloid deposits of Alzheimer's disease. AB - The pathological findings of Alzheimer's disease include amyloid deposition in cerebral blood vessels and in senile plaques. Both deposits are known to include peptides that contain a common sequence. Both forms of amyloid were isolated and their peptide compositions were determined. The peptides were resolved by size exclusion chromatography in 70% formic acid, and reverse-phase chromatography in 60% formic acid, 0-40% acetonitrile. Senile plaque amyloid cores contain about 25% protein, about 70% of which is composed of peptides containing the beta amyloid sequence. Amino-terminal sequencing of the core amyloid peptides (CAPs) revealed extensive amino-terminal heterogeneity, with variable amounts of blocked amino termini. Matrix-assisted, laser-desorption-time-of-flight mass spectrometry of the CAP mixture revealed an array of peptides the molecular weights of which corresponded to peptides beginning with each of the first 11 amino acids of the beta-peptide sequence and ending with Ala-42 of that sequence. The carboxyl terminal residues were identified by tandem mass spectrometry of chymotrypsin digests. CAP possessed a minor degree of carboxyl-terminal heterogeneity. Cerebrovascular amyloid peptides (CVAPs) possessed minor degrees of both amino- and carboxyl-terminal heterogeneity. The major CVAP commenced at Asp-1 and ended at Val-40. Minor components of CAP possessed masses of 8000-9000 Da and the same amino-terminal residues as the major components of CAP. They may be precursors to the smaller CAPs. The differences in amino termini and carboxyl termini of CAPs and CVAPs suggest that the two types of amyloid form by different pathways, on which they encounter different proteases. PMID- 8442666 TI - Production and characterization of polyclonal antibodies in rabbits to 4S limonene synthase from spearmint (Mentha spicata). AB - Limonene synthase, a monoterpene cyclase from the oil glands of spearmint (Mentha spicata) leaves that catalyzes the conversion of geranyl pyrophosphate to (-)-4S limonene, was purified, and polyclonal antibodies were generated in rabbits against the sodium dodecyl sulfate-denatured protein. Immunoblotting analysis revealed that the antibodies were very specific for denatured limonene synthase from all Mentha species tested. However, no immunological cross-reactivity was observed with denatured limonene synthases from Valencia oranges (Citrus sinensis, Rutaceae) or wormseed (Chenopodium ambrosioides, Chenopodiaceae). Furthermore, the antibody preparation did not detectably cross-react with other monoterpene cyclases from related angiosperm species of the Lamiaceae, Asteraceae, and Umbellifereae, or from conifer species, and no cross-reactivity was demonstrated toward several sesquiterpene cyclases of higher plant and fungal origin. Although the antibody preparation was highly selective for denatured limonene cyclase from Mentha, the antibodies did not recognize the native protein in several different types of experiments. Nevertheless, specificity for the target enzyme was unambiguously demonstrated when the antibody preparation was shown to cross-react with the cyclase protein expressed in Escherichia coli that harbored the corresponding limonene synthase cDNA gene from M. spicata. PMID- 8442667 TI - Regulation of the mitochondrial ATP synthase/ATPase complex: cDNA cloning, sequence, overexpression, and secondary structural characterization of a functional protein inhibitor. AB - The ATPase inhibitor protein of the rat liver mitochondrial ATP synthase/ATPase complex has been cloned from a rat liver cDNA library, and its nucleotide sequence determined. The sequence is highly homologous to both the bovine heart (approximately 70%) and the yeast inhibitor proteins (approximately 40%). The deduced protein sequence is 107 amino acids in length, and based on homology to the bovine heart protein, the first 25 N-terminal amino acids encode a putative mitochondrial targeting sequence. The "mature" protein (without the targeting sequence) fused to the maltose binding protein has been overexpressed in Escherichia coli. The maltose binding protein was used as a handle for the development of a rapid one-step purification of the fusion protein by affinity chromatography on an amylose resin. The purified fusion protein was cleaved with Factor Xa protease at the fusion junction, and the resulting ATPase inhibitor protein was purified to > 90% purity. The purified, overexpressed inhibitor protein displays normal inhibitor activity. The protein inhibits ATP hydrolysis catalyzed by the ATP synthase/ATPase complex in submitochondrial particles in a manner kinetically indistinguishable from the same protein purified from rat liver mitochondria, and exhibits a specific activity of approximately 10,000 units/mg. The secondary structure of the inhibitor protein was determined by circular dichroism spectropolarimetry. The experimentally determined structure shows a high content of alpha-helix and is in good agreement with sequence-based structural predictions. As the function of the inhibitor protein is known to exhibit a high dependence on pH, a study of the pH dependence of inhibitor secondary structure was performed. It is shown that as pH is lowered, conditions which activate inhibitory capacity, the protein loses significant alpha-helical structure. This is the first report of the overexpression in E. coli of a functional ATPase inhibitor protein. Secondary structural analysis of this protein indicates that conversion from its active to its inactive form involves a significant conformational change. PMID- 8442669 TI - Morphometric analysis of benign and malignant adrenal pheochromocytomas. AB - At present, there are no reliable histologic features that can predict malignancy in adrenal pheochromocytomas other than the documentation of metastases. With the use of computerized interactive morphometry, our aim was to assess nuclei from tissue sections of confirmed cases of benign and malignant pheochromocytomas to determine whether consistent quantitative differences existed between the two. Eight benign cases with at least a 5-year follow-up and nine malignant cases with documented metastases were evaluated. Size distribution plots of the maximum nuclear cord length and of the nuclear area showed a narrow peak for the malignant cases, whereas benign cases showed a right-shifted curve with a wider peak. We concluded that nuclear morphometric analysis of benign and malignant pheochromocytomas yields two distinctive patterns and may be of utility in the assessment of future cases. PMID- 8442668 TI - Structural heterogeneity of Caucasian N-acetyltransferase at the NAT1 gene locus. AB - The human N-acetylation polymorphism is a genetic trait phenotypically reflected by differences in N-acetyltransferase (NAT) activity with therapeutic agents (rapid and slow acetylation), but a genetic invariability in N-acetylation of some arylamine drugs is also known. There are two highly similar human NAT genes: NAT1 is thought to encode a genetically invariant protein, whereas NAT2 has conclusively been shown to represent a polymorphic locus. This study demonstrates the presence of discrete NAT1 structural variants among Caucasians. These were detected by direct sequencing of 1.6-kilobase NAT1 fragments generated by the polymerase chain reaction with liver and leukocyte DNA from 13 subjects of established acetylator phenotype and NAT2 genotype. A prominent alteration in one of the variants was obliteration of the consensus polyadenylation signal (AATAAA- >AAAAAA). Several mutations were discernible in all regions of the second variant allele, including silent (codon 153) and nonsilent (Ser-214-->Ala) substitutions in the coding region and deletion of nine bases from an AT-rich segment in the 3' untranslated region. One-half of the unrelated subjects were either homozygous or heterozygous for the mutant NAT1 alleles, both of which obeyed a Mendelian inheritance pattern. These novel results unambiguously show that human NAT1, like NAT2, is a polymorphic locus. PMID- 8442670 TI - Beta-endorphin, steroids, and prolactin. Immunoassay in breast cysts and blood. AB - Circulating levels and cyst fluid concentrations of beta-endorphin (beta-EP), estradiol, progesterone, and prolactin were measured by radioimmunoassays in 10 premenopausal women with gross breast cysts. In addition, aspirates and frozen tissue sections from cystic lesions were investigated immunocytochemically for a possible beta-EP production. Epithelia of dilated ducts, smaller cysts, and hyperplastic lesions without atypia showed a strong positive reaction in the cytoplasm. In apocrine metaplasia, this staining was concentrated in the apical region. The staining intensity in atypical hyperplasia was diminished. Occasionally, normal duct and lobular epithelia exhibited positive beta-EP immunostaining. Levels of beta-EP, estradiol, and progesterone in the cyst fluid were significantly higher than in blood, but no significant differences were observed for prolactin. The ratios of progesterone to estradiol, estradiol to prolactin, and progesterone to prolactin in the cyst fluid were considerably higher than in blood. This suggests that beta-EP and steroid hormones are secreted from the lining epithelia into the breast cysts. PMID- 8442671 TI - Florid extravascular papillary endothelial hyperplasia (Masson's pseudoangiosarcoma) presenting as a soft-tissue sarcoma. AB - Papillary endothelial hyperplasia (also known as Masson's pseudoangiosarcoma) is a hyperplastic proliferation of endothelial cells that is usually an incidental finding within thrombosed dilated blood vessels or vascular tumors. Rare extravascular forms occur and can histologically closely mimic angiosarcoma. We report a case of extravascular papillary endothelial hyperplasia that extensively involved a large, traumatic, deep soft-tissue hematoma in a 19-year-old man and clinically presented as a soft-tissue sarcoma. We also summarize characteristics of 314 cases of papillary endothelial hyperplasia reported in the literature and identify 13 likely cases of the rare extravascular form. PMID- 8442672 TI - HMB-45 antibody demonstrates melanosome specificity by immunoelectron microscopy. AB - The intracellular localization of antigenic sites recognized by the monoclonal antibody HMB-45 was investigated in melanomas of the choroid and skin by postembedding immunoelectron microscopy. Antigenic sites were detected by a three step procedure, consisting of incubating sections with the monoclonal HMB-45 antibody (protein G affinity-purified ascites from Enzo Diagnostics Inc or tissue culture supernatant from Dako Corp), followed by incubation with an affinity purified rabbit anti-mouse IgG and finally with protein A-gold complex. Gold particles, indicative of HMB-45 immunoreactivity, were restricted to melanosomes in the malignant melanocytes. Early stages in melanosome formation (stages I through III) were most intensely stained, while late-stage melanosomes (stage IV) were only sparsely labeled or not stained at all. Melanophages adjacent to a cutaneous melanoma showed intense immunoreactivity in the cytoplasm and especially over electron-dense portions of lysosomes with the HMB-45 antibody from Enzo. In marked contrast, only very sparse labeling was detected over melanophages using a similar concentration of the HMB-45 antibody from Dako. Subsequently, when the Enzo antibody was diluted 40 times above the recommended working dilution, most of the melanophage staining disappeared, while melanocyte specific staining was maintained. Immunolabeling of melanosomes with HMB-45 was drastically reduced or absent following section pretreatment with neuraminidase, confirming an earlier report that the HMB-45 antigen is partially composed of sialic acid. Our immunoelectron microscopic results show that HMB-45 antibody specifically stains melanosomes, rather than diffuse cytoplasmic antigen, as described by light microscopic immunohistochemical analysis, thus explaining its specificity for melanocytes. In addition, the elimination of HMB-45 immunoreactivity by neuraminidase pretreatment supports the idea that sialylation of antigen is crucial to HMB-45 binding, and suggests that the absence of staining in normal adult melanocytes, dermal nevi, and other melanocytic lesions may be a result of differential sialylation. PMID- 8442673 TI - Calcified spherules in fibro-osseous lesions of bone. AB - We present 20 examples of fibro-osseous lesions of bone, characterized by the presence of varying numbers of rounded calcified structures (calcified spherules). In the past, such lesions have been regarded as ossifying fibromas or cementifying fibromas, the latter because of their histologic similarity to jaw lesions known by that name. In the present series, six lesions showed, in addition to the calcified spherules, typical histologic features of fibrous dysplasia, while a further seven showed atypical bony structures that also suggest a link with fibrous dysplasia. This study has led us to conclude that these lesions of the extragnathic skeleton, containing rounded calcified spherules, represent a variant of fibrous dysplasia. PMID- 8442674 TI - Lipothymoadenoma of the parathyroid. AB - We describe the clinical and morphological features of a most unusual functional mediastinal tumor that combines features of thymolipoma and lipoadenoma of the parathyroid gland. The lesion was unique in that microscopic elements of benign thymic, adipose, and parathyroid tissue were admixed intimately in one partially encapsulated mass. To the best of our knowledge, there has not been a previous description of this tumor. It was excised from a 54-year-old woman with a 10-year history of persistent hyperparathyroidism. The controversial relationship of embryological malformation, hamartoma, and neoplasm is exemplified by this entity. PMID- 8442675 TI - Epithelioid hemangioendothelioma with osteoclastlike giant cells. AB - This article describes histopathologic and immunohistologic features of an epithelioid hemangioendothelioma that presented in the neck of a 40-year-old man. This tumor was unusual because of the presence of osteoclastlike giant cells scattered throughout the entire lesion. The tumor cells reacted positively for factor VIII-related antigen, and the osteoclastlike giant cells were reactive for KP1 antibody, a macrophage-associated antigen. We are aware of only one other previously reported example of soft-tissue epithelioid hemangioendothelioma with an abundance of osteoclast-like giant cells. PMID- 8442676 TI - Ossifying seminoma of the testis. AB - A 55-year-old Hispanic man presented with a large testicular mass with metastases to pelvic and retroperitoneal lymph nodes and bones. Computed tomographic scans revealed calcifications in the testis and lymph nodes. The orchiectomy specimen showed a seminoma with extensive ossifications. The amount of bone formation, believed to represent a degenerative phenomenon, is extremely unusual and, to the best of my knowledge, has not been presented in the literature. PMID- 8442677 TI - A new variant of lethal neonatal short-limbed platyspondylic dwarfism. AB - This article describes an unusual skeletal dysplasia in a male fetus diagnosed by ultrasound at 18 weeks of gestation. The clinical and radiologic findings resemble thanatophoric dysplasia. Histologic examination revealed abnormalities in the resting cartilage, physeal growth plate, and bone. The resting cartilage contained peculiar large chondrocytes with huge lacunae. The growth plate revealed absence of column formation and hypertrophic vacuolated chondrocytes extending far into the metaphyseal bone trabeculae. The bone was hypercellular with absence of lamellar bone. The cortical bone was scanty and woven. The histopathologic features are, therefore, unique and differ from all other well recognized varieties of short-limbed platyspondylic dwarfism. PMID- 8442678 TI - Placental involvement by maternal non-Hodgkin's lymphoma. AB - We report a case of non-Hodgkin's lymphoma with placental metastasis. A 42-year old pregnant women was diagnosed with non-Hodgkin's lymphoma at 26 weeks' gestation by needle-aspiration biopsy of the lung. She later delivered a boy at 28 weeks' gestation; however, despite resuscitation he died soon after birth. Histopathologically, we found malignant lymphoma cells invading the intervillous space of the placenta, but an autopsy on the neonate was not authorized. The patient died 10 months later of widespread malignant lymphoma, confirmed by autopsy. This case is interesting, since malignancy during pregnancy is rare, and even more infrequent are cases of maternal malignant lymphoma with placental metastasis. PMID- 8442679 TI - Lessons learned. PMID- 8442680 TI - Restoration, not preservation, of general surgery residency. PMID- 8442681 TI - Recurrent cholangitis with and without anastomotic stricture after biliary enteric bypass. AB - We recently surgically treated 24 patients incapacitated by recurrent cholangitis after biliary-enteric anastomosis performed for benign disease. Contrary to commonly held dogma, as many as one third of the patients had no evidence of anastomotic stricture indicated by radiologic and operative findings. We identified several other primary and coexistent pathogenetic factors including intrahepatic stricture in 42% of the patients, intrahepatic calculi in 25%, improperly constructed enteric conduits in 13%, and conditions that predispose to bacterial overgrowth in the biliary tree in 17%. Seventy-one percent of the patients had multiple etiologic factors, and of those patients without demonstrable anastomotic stricture, intrahepatic stricture was particularly common. Seventy-one percent remained symptom-free in their first year after operation. The most difficult situation to manage, and the factor responsible for most recurrences after our reoperation, involved intrahepatic stricture. A combined surgical and interventional radiologic approach to complex cases may be useful in selected patients. PMID- 8442682 TI - Transplant rejection. Mechanisms and treatment. AB - In this review, we summarize the cellular and molecular events in the rejection of transplanted allografts, as well as the rationale for the evolving techniques to suppress such rejection. Allogenic major histocompatibility complex antigens expressed on the allograft and/or on the "passenger leukocytes" within the graft are the major antigenic stimuli recognized as being foreign by receptors of CD4+/T helper cells of the host. Host macrophages provide a second signal, interleukin (IL) 1, essential to the activation of T helper cells. Subsequent production of IL-2 by T helper cells leads to activation and proliferation of cytotoxic T cells and lymphokine-activated killer cells and the release of IL-4 and IL-6. In addition, IL-2 promotes release of interferon gamma as well as tumor necrosis factor and other proinflammatory cytokines. Therapeutic options to "downregulate" this cascade have gradually evolved from global nonspecific immunosuppressive techniques (total body irradiation, antilymphocyte serum) to increasingly specific modalities currently being studied, including monoclonal antibodies against the IL-2 receptor (thus targeting only vigorously proliferating T cells), antibodies against specific cytokines (interferon gamma, tumor necrosis factor), and now "designer" antibody-toxin conjugate molecules that deliver toxins to selected receptor targets. Finally, work continues toward inducing preoperative antigen-specific (graft) tolerance, including utilization of gene transfection techniques to transfect donor major histocompatibility complex antigens to recipients before surgery, which has been shown to prolong murine cardiac allografts, perhaps by priming specific suppressor cells. Further understanding of the initiation of, and subsequent events in, transplantation rejection will lead to increasingly effective prolongation of graft survival while minimizing adverse effects on the host. PMID- 8442683 TI - Long-term follow-up of positive cultures in 500 abdominal aortic aneurysms. AB - Routine aneurysm culture is frequently performed as it is thought that a positive culture could be a risk factor for secondary graft infection. Five hundred aneurysms, in a series of 796 patients, had microbiologic examination of the thrombus and/or aneurysm wall. Cultures were positive in 185 cases (37%), mostly due to normal skin flora microorganisms (80%), whereas 16 patients (3.2%) had infectious aortitis. Gram-stained smears were positive in nine of these 16 patients compared with two of the other 169. Of the 185 patients with positive culture, after a mean length of follow-up of 35 months, only one had a graft infection that occurred 6 years later and was not due to the same microorganism. Graft sepsis was diagnosed in six of the 296 patients who did not have a positive culture, and was related to clinically obvious locoregional or systemic foci. In this series, positive cultures from aneurysm without rupture or signs of infection were not a risk factor for secondary graft sepsis. Therefore, in cases of asymptomatic unruptured aneurysm, routine culturing is not necessary as a positive result has no pathogenic significance or therapeutic implication. PMID- 8442684 TI - Can patients with minor head injuries be safely discharged home? AB - To identify all patients with serious intracranial injury, current treatment strategies include admission and/or computed tomographic evaluation of all patients with head injuries. However, the majority of patients with head injuries who are awake do not require subsequent intervention. A review of 407 consecutive patients with head injuries treated at an adult regional trauma center identified 310 patients with Glasgow Coma Scores of 15 in the emergency department, all of whom were admitted. Five patients with Glasgow Coma Scores of 15 required intervention for intracranial abnormality. All five patients had skull fractures and/or neurologic deficits. Based on this and other studies, criteria for discharge from the emergency department are a Glasgow Coma Score of 15, no deficit except amnesia, no signs of intoxication, and no evidence of basilar fracture on clinical examination or linear fracture on screening skull roentgenography. Safe discharge without universal computed tomographic evaluation or admission is possible and cost-efficient. PMID- 8442685 TI - Microvasculature of the pancreas, liver, and kidney in cerulein-induced pancreatitis. AB - Edematous pancreatitis was induced in 12 male Sprague-Dawley rats using supramaximal doses of the cholecystokinin analogue cerulein (5 micrograms/kg per hour). The microvasculature of the pancreas, liver, and kidney was examined using scanning electron microscopy of microvascular corrosion casts in 12 test animals and four controls at intervals of 30 minutes, 1 hour, 2 hours, and 4 hours. Distortion of the pancreatic and hepatic microvasculature was seen as early as 30 minutes and progressed during the study period. The renal vasculature remained normal throughout. Light microscopic analysis revealed no morphologic abnormalities in the walls of the pancreatic, hepatic, or renal microvasculature. This study demonstrates that cerulein-induced pancreatitis is associated with marked distortion of the pancreatic and hepatic microvasculature; the abnormalities start early in the disease and progress during the study period. PMID- 8442686 TI - Dipyridamole thallium imaging in patients being considered for vascular procedures. AB - We routinely performed intravenous dipyridamole thallium imaging and resting radionuclide ventriculography on 190 patients being considered for elective vascular procedures. Patients with thallium redistribution underwent coronary arteriography. Patients in group 1 (n = 78) had clinical evidence of coronary artery disease, and patients in group 2 (n = 112) had no history or electrocardiographic evidence of coronary artery disease. The frequency of thallium redistribution was not significantly different in the two groups (45% in group 1 and 46% in group 2). Coronary arteriography identified severe three vessel or left main disease in eight patients (10%) in group 1 and 16 patients (14%) in group 2. Selection of patients for dipyridamole thallium imaging prior to vascular reconstruction should be based on whether or not documentation of the extent of coronary artery disease would influence therapy rather than on clinical indicators of coronary disease. PMID- 8442687 TI - A youth violence prevention program. Description and preliminary evaluation. AB - PROBLEM STATEMENT: In response to growing violence, primary prevention programs have been launched, but scientific rationale and credible evaluations have been lacking. METHODS: Fifth and seventh-grade students in three inner-city schools (n = 135) participated in a violence prevention program. Controls consisted of students from the same schools and grades during the following school year (n = 115). Students were taught social problem-solving skills and risk factors for violence. Multivariate analyses were performed on posttest measures while controlling for base-line differences. RESULTS: Program participants were much less likely to define social problems in adversarial ways, were less likely to provide violent solutions in hypothetical conflict situations, listed more negative consequences to using violence, and were less inclined to legitimatize violence. Risk factor knowledge also was significantly increased. No increase was shown in the students' abilities to identify viable nonviolent solutions. CONCLUSIONS: The program produced immediate influences on knowledge and some attitudes and social skills shown to be related to aggressive behavior. PMID- 8442688 TI - Prognosis of patients with breast cancer related to the timing of operation. AB - Whether the timing of mastectomy during the menstrual cycle influences the prognosis of premenopausal women with breast cancer is controversial. We retrospectively reviewed the cases of 97 regularly menstruating women treated for operable stages of breast cancer. At operation, 55 women were in the perimenstrual phase of the menstrual cycle (days 0 through 6 and days 21 through 36) and 42 were in the periovulatory phase (days 7 through 20). No relationship could be identified between the timing of surgical treatment and subsequent recurrence or survival. The timing of biopsy was also not associated with prognosis. We conclude that no delay of surgical treatment for breast cancer need be based on the phase of the menstrual cycle of premenopausal women. PMID- 8442689 TI - The value of flow cytometric analysis in patients with gastric cancer. AB - Tumors in the gastric cardia and the body/antrum were studied to determine the effect of ploidy and S-phase fractions on patient survival. Forty-two percent of tumors were located in the cardia and 58% in the body/antrum. Nodal metastases occurred more often with cardia tumors than with body/antrum tumors (86% vs 65%). Aneuploidy occurred more frequently in patients with cardia tumors than in patients with body/antrum tumors (39% vs 20%). Metastasis to lymph nodes was more common in patients with aneuploidy than in patients with diploidy (31% vs 7%). S phase fractions were not different between aneuploid and diploid tumors. More patients with diploid cancer were alive at 5 years than were patients with aneuploid tumors (90% vs 10%). We conclude that primary cellular differences in gastric tumors of the cardia or body/antrum determine patient survival. PMID- 8442690 TI - Administration of dehydroepiandrosterone to burned mice preserves normal immunologic competence. AB - Burned individuals display a reduced ability to elicit cellular and humoral immune responses and a depression in the vitro production of certain T-cell lymphokines. Treatment of burned mice with 100 micrograms of dehydroepiandrosterone within 1 hour after injury resulted in preserving a completely normal capacity to produce T-cell-derived lymphokines and to generate cellular immune responses. In addition, dehydroepiandrosterone-treated thermally injured mice demonstrated an above-normal ability to resist an induced infection with the intracellular pathogen, Listeria monocytogenes. Dehydroepiandrosterone treated animals also did not exhibit the sustained plasma levels of interleukin 6 that normally accompany thermal injury and infection. Because of its antiglucocorticoid effects and positive immunoregulatory influences, we believe dehydroepiandrosterone to be a beneficial form of therapy for thermally injured individuals. PMID- 8442691 TI - Do surgical and endoscopic sphincterotomy prevent or facilitate recurrent common duct stone formation? AB - The possible formation of brown recurrent common duct stones (RCS) as a long-term side effect of sphincterotomy (SPHT) has been evaluated in 63 patients with stone formation after cholecystectomy, 253 who underwent SPHT or choledocholithotomy, 131 with postoperative monitoring of bile bacteriologic characteristics through the T tube, and 20 with stone and bile analysis at both operations. In addition, findings are also reported in 145 patients who underwent surgical SPHT and radiologic review of up to 28 years after surgery, five who underwent ampullectomy, and 55 who underwent endoscopic SPHT. The RCS were usually brown (72.5% of cases), and were always associated with bile infection caused by Escherichia coli. Sixty-two percent of brown RCS were found after SPHT. Eleven percent of patients who underwent surgical SPHT, 9% who underwent endoscopic SPHT, and 66.6% who underwent ampullectomies had brown RCS. Sphincterotomy determined a fivefold greater incidence of postoperative bactibilia, and a seven fold greater incidence of brown RCS, than did choledocholithotomy. It is suggested that: (1) since brown RCS are secondary to bile contamination from the duodenum, SPHT (and subsequent stricture), facilitating both bile contamination and bacterial overgrowth, could be considered a basic factor in the formation of these stones; and (2) since true RCS are mostly of the brown subtype, SPHT could prevent the occurrence of retained stones by flushing the stones that were missed during the first operation, but undoubtedly increases the total incidence of RCS. PMID- 8442692 TI - Liver transplantation for Alagille's syndrome. AB - Twenty-three children with Alagille's syndrome and end-stage liver disease underwent liver transplantation with cyclosporine and low-dose steroid immunosuppression. Two to 9 years (mean, 4.4 years) after surgery, 13 (57%) of the children were still alive, with normal liver function. Three of the fatalities were due to cardiovascular failure secondary to associated cardiopulmonary disease. Mortality was higher among patients who had more severe cardiac disease and patients who had previously undergone a Kasai procedure. Although it has a higher than average risk, liver transplantation can be efficacious in patients with Alagille's syndrome and end-stage liver disease. PMID- 8442693 TI - Acute thrombosis of the splanchnic veins. AB - The consequence of an acute thrombosis in the splanchnic veins on the viability of the intestine has not been well defined in the literature. Spontaneous recovery or total necrosis of the bowel have both been described. We treated seven patients with thrombosis of the splanchnic veins and adopted a surgical approach in three patients with extended and complete thrombosis of the superior mesenteric vein, portal vein, and splenic vein, while four patients with partial thrombosis of the superior mesenteric vein or protal vein recovered with conservative treatment. A 22-year literature review has identified 64 cases of acute thrombosis in the splanchnic veins, with complete information regarding the location and extent of the thrombosis, the treatment, and the outcome. Different anatomical patterns of thrombosis with mortality rates varying between 0% and 76% seem to be related to the extent and completeness of venous obstruction. PMID- 8442694 TI - Unilateral renal artery stenosis seen initially as severe and symptomatic hypokalemia. Pathophysiologic assessment and effects of surgical revascularization. AB - Hypokalemia is an uncommon presentation of renovascular hypertension. Although renal artery stenosis has been associated with hypokalemia secondary to hyperreninemic hyperaldosteronism, few reports have actually evaluated the pathophysiologic changes in such a patient with renovascular hypertension. We studied a patient before and after surgical revascularization who presented with severe hypertension and marked, symptomatic hypokalemia. Before surgery, the patient had excessive urinary potassium secretion, markedly increased secretion of renin after captopril stimulation, and mild secondary hyperaldosteronism. Postoperatively, the patient's blood pressure decreased moderately and the serum and urinary potassium values normalized. After revascularization, plasma renin activity both before and after captopril stimulation and serum aldosterone levels decreased markedly. These findings demonstrate that renovascular hypertension may rarely present with symptomatic hypokalemia secondary to excessive aldosterone secretion. Improvement in the renal ischemic state is accompanied by rapid correction of the metabolic disturbances associated with hyperreninemic hyperaldosteronism. PMID- 8442695 TI - Intrahepatic portohepatic venous shunt. A case report of successful surgical resection. AB - Symptomatic intrahepatic portohepatic venous shunts are rare. We report a case with shunting isolated in the right lobe. The lesion was clearly depicted with sonography and was successfully resected using echoguidance. Using this case and a review of the literature, we propose a management approach for this rare lesion. PMID- 8442696 TI - Sclerosing encapsulating peritonitis combined with peritoneal encapsulation. AB - The combined occurrence of idiopathic sclerosing encapsulating peritonitis and peritoneal encapsulation is described. A 52-year-old man presented with intestinal obstruction. The results of preoperative examinations were suggestive of sclerosing encapsulating peritonitis. Laparotomy revealed the concurrence of peritoneal encapsulation and sclerosing encapsulating peritonitis. The thick membrane of sclerosing encapsulating peritonitis was freed with multiple incisions. After operation, the patient reverted to the preoperative state. The condition, however, was alleviated with conservative therapy consisting of intravenous hyperalimentation and nasogastric suction. To our knowledge, the combined occurrence of sclerosing encapsulating peritonitis and peritoneal encapsulation has never before been reported. PMID- 8442697 TI - Laparoscopist's thumb: an occupational hazard. PMID- 8442698 TI - End-diastolic volume. PMID- 8442699 TI - Babinski yes, Hachinski no. PMID- 8442700 TI - Specificity of the upgoing thumb. PMID- 8442701 TI - Neurosyphilis. A comparative study of the effects of infection with human immunodeficiency virus. AB - BACKGROUND: The course of neurosyphilis has been reported to be altered by human immunodeficiency virus (HIV) infection. Prior reports of neurosyphilis occurring in association with HIV infection have been largely anecdotal and have failed to compare neurosyphilis in patients with HIV infection with an uninfected control group. This study was performed to determine if the clinical presentation encountered is different in the presence of HIV infection. DESIGN: A retrospective, hospital-based, case series study based on chart review encompassing a 64-month period. SETTING: The study was performed in a large, university-affiliated, public health trust hospital in south Florida. PATIENTS: Forty-six hospitalized patients with neurosyphilis were identified; 13 patients fulfilled Centers for Disease Control and Prevention (Atlanta, Ga) criteria for acquired immunodeficiency syndrome (AIDS), 11 were HIV seropositive only, and 22 were HIV uninfected. Neurosyphilis was determined by a reactive cerebrospinal fluid VDRL slide test. RESULTS: The HIV-infected patients (both AIDS and HIV seropositive groups) were younger and more frequently had features of secondary syphilis, such as rash, fever, adenopathy, headache, or meningismus. Significant differences were observed in cerebrospinal fluid measurements when the HIV infected group was compared with the HIV-uninfected group, including a higher mean white blood cell count in patients with AIDS and a higher mean protein level and a lower mean glucose level in the HIV-infected group. Syphilitic meningitis was more common in HIV-seropositive patients, although the HIV-uninfected patients presented with a greater variety of types of neurosyphilis. Ophthalmic syphilis was observed more frequently in the HIV-infected group. CONCLUSIONS: Significant differences exist between neurosyphilis occurring in the presence and absence of HIV infection. PMID- 8442702 TI - Magnetic resonance imaging morphometric analysis of cerebral volume loss in human immunodeficiency virus infection. The HNRC Group. AB - Magnetic resonance imaging was used to compare male subjects seropositive for antibody to human immunodeficiency virus type 1 (HIV positive), with and without medical symptoms, with two groups of men who were seronegative (HIV negative). The control subjects included men at high risk for exposure to HIV-1 and those at low risk. None of the HIV-positive subjects met criteria for HIV-associated dementia or had detectable opportunistic brain disease. Quantitative image analytic techniques were used to estimate volumes of ventricular and cortical cerebrospinal fluid, cerebral white matter, and cortical and subcortical gray matter structures. Relative to low-risk group control subjects and asymptomatic HIV-positive subjects, nondemented but medically symptomatic HIV-positive subjects showed significant increases in cerebrospinal fluid, reduced volume of cerebral white matter, and reduced cerebral gray matter volumes. Unexpectedly, however, some cerebrospinal fluid increases and gray matter volume decreases were present in the seronegative high-risk control subjects as well. PMID- 8442703 TI - Role of predisposing and protective HLA-DQA and HLA-DQB alleles in Sardinian multiple sclerosis. AB - OBJECTIVE: To study the role of HLA genes in susceptibility and resistance to multiple sclerosis (MS) in Sardinian patients. To verify whether HLA-DQA and HLA DQB genes differed between unrelated (MSU) and related (MSR) patients, and whether relapsing-remitting and chronic progressive forms of MS are immunogenetically distinct entities. DESIGN: Case-control study of HLA-DQA and HLA-DQB gene frequency. SETTING: All patients investigated were followed up by our MS referral centers. PATIENTS: The study involved 116 MSU patients, 67 of whom had a relapsing-remitting form (MSr), 28 of whom had a chronic progressive from-the-onset form (MSc), and 21 of whom had a benign form (MSb), 32 patients with MSR, 19 parents and 27 healthy siblings of patients with MSR, and 86 controls. Selection of patients was random, while control subjects came from families without known immunologic diseases. All patients had definite MS. MAIN OUTCOME MEASURE: Statistical analysis of gene frequencies was conducted with the chi 2 test with correction (Pc) for the alleles investigated, as was decided before the study began. RESULTS: The DQA1*0301 allele was found to be increased in patients (MSU vs controls, Pc = .008; patients with MSc vs controls, Pc = .001; patients with MSR vs controls, Pc = .02; and parents vs controls, Pc = .04), while the DQA1*0102 allele was found to be diminished in patients with MSr vs controls (Pc = .001). Among the DQB genes, the DQB1*0502 allele was diminished in patients with MSr vs controls (Pc = .04), while the sum of DQB1*0201 and *0302 alleles was significantly increased in patients with MSR vs controls (Pc = .003). CONCLUSION: Both HLA-DQA and HLA-DQB genes influence genetic susceptibility and resistance to MS. The roles of these genes differ in the various forms of MS. Patients with MSU and MSR both share HLA-DQA susceptibility genes. PMID- 8442704 TI - Treatment of leptomeningeal metastasis with intraventricular administration of depot cytarabine (DTC 101). A phase I study. AB - Depo cytarabine (DTC 101 [formerly identified as Depo/Ara-C]) is a slow releasing, depot formulation in which cytarabine is encapsulated within the aqueous compartments of microscopic (DepoFoam) particles. A phase I trial of DTC 101, given intraventricularly, was conducted in patients with leptomeningeal metastasis. Nine patients were given 1 to 7 cycles of DTC 101 in doses ranging from 25 to 125 mg that were administered via an Ommaya reservoir into the lateral ventricle. The dose-limiting toxic reaction was encephalopathy that occurred at the 125-mg dose level. All toxic episodes but one were transient and reversible, with the total duration of toxicity lasting from 1 to 7 days. The ventricular concentration of free cytarabine released from DTC 101 into cerebrospinal fluid decreased biexponentially with an initial half-life of 7.2 +/- 1.7 (+/- SEM) hours and a terminal half-life of 140 +/- 49 hours. The cerebrospinal fluid was cleared of malignant cells within 3 weeks of initial therapy in five of six cytologically evaluable patients. The duration of response ranged from 2 to more than 14 weeks, with a median of over 11 weeks. In conclusion, DTC 101 appears to be a pharmacologically attractive agent for use against leptomeningeal metastasis. The toxic episodes that occur with this therapy are well tolerated by patients. PMID- 8442705 TI - The clinical spectrum of unruptured intracranial aneurysms. AB - OBJECTIVE: A retrospective study was performed to delineate the clinical characteristics of symptomatic unruptured aneurysms. DESIGN: Patient histories, operative reports, and angiograms in 111 patients with 132 unruptured aneurysms were reviewed. SETTING: Tertiary care university hospital. PATIENTS: One hundred eleven patients with 132 unruptured intracranial aneurysms were studied. There were 85 women and 26 men, with a mean age of 51.2 years (age range, 11 to 77 years). Many patients were referred by community neurologists and neurosurgeons for further evaluation and neurosurgical management. RESULTS: Fifty-four symptomatic patients were identified. Group 1 (n = 19; mean aneurysm diameter, 2.1 cm) had acute symptoms: ischemia (n = 7), headache (n = 7), seizure (n = 3), and cranial neuropathy (n = 2). Group 2 (n = 35; mean aneurysm diameter, 2.2 cm) had chronic symptoms attributed to mass effect: headache (n = 18), visual loss (n = 10), pyramidal tract dysfunction (n = 4), and facial pain (n = 3). Group 3 (n = 57; mean aneurysm diameter, 1.1 cm) had asymptomatic aneurysms. CONCLUSIONS: Acute severe headache, comparable to subarachnoid hemorrhage headache, but without nuchal rigidity, was associated with the following mechanisms: aneurysm thrombosis, localized meningeal inflammation, and unexplained. Unruptured aneurysms may be misdiagnosed as optic neuritis or migraine, or serve as a nidus for cerebral thromboembolic events. Internal carotid artery and posterior circulation aneurysms were more likely to cause focal symptoms from mass effect than were anterior cerebral artery and middle cerebral artery aneurysms. Weeks to years may elapse before their diagnosis. The absence of subarachnoid blood does not exclude an aneurysm as a cause for acute or chronic neurologic symptoms. PMID- 8442706 TI - The syndrome of mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes presenting without stroke. AB - OBJECTIVE: To study and describe a large family with the tRNA Leu(UUR) point mutation at position 3243 in mitochondrial DNA, which is associated with the syndrome of mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes. DESIGN: Survey; case series. SETTING: University hospital inpatient and outpatient neurology department. PATIENTS: Twelve patients from three generations in a family carrying the tRNA Leu(UUR) point mutation at position 3243 were studied. INTERVENTIONS: Clinical evaluation, muscle biopsy, and mitochondrial DNA point mutation quantitation of the syndrome of mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes in muscle and blood. MAIN OUTCOME MEASURE: Correlation between clinical, pathologic, and genotypic features. RESULTS: Family members had various combinations of sensorineural hearing loss, retinal pigmentary degeneration, migraine, hypothalamic hypogonadism, and mild myopathy. Only one member had a strokelike episode at the age of 46 years. This patient had the highest point mutation percentage. CONCLUSION: This report suggests that this point mutation may not be associated with stroke in all families and that whether patients develop stroke may depend on the percentage of mutant mitochondrial DNA and its tissue distribution. PMID- 8442707 TI - Architecture of connectivity within a cingulo-fronto-parietal neurocognitive network for directed attention. AB - The spatial distribution of directed attention is coordinated by a large-scale neural network. The three principal cortical components of this network are located in the region of the frontal eye fields, posterior parietal cortex, and the cingulate cortex. We injected a retrogradely transported fluorescent dye into the frontal eye fields and another into the posterior parietal cortex of the monkey brain. Large numbers of neurons in the cingulate cortex were retrogradely labeled with each of the two fluorescent dyes. The two types of retrogradely labeled neurons were extensively intermingled, but neurons labeled with both tracers constituted less than 1% of retrogradely labeled cingulate neurons. Other cortical areas that contained retrograde neuronal labeling included the premotor, lateral neuronal labeling included the premotor, lateral prefrontal, orbitofrontal, opercular, posterior parietal, lateral temporal, inferior temporal, parahippocampal, and insular regions. These areas contained neurons labeled with each of the two dyes but virtually no neurons labeled with both. In the thalamus, retrogradely labeled nuclei failed to display evidence of double labeling. The overlap between the two populations of retrogradely labeled neurons was far more extensive at the cortical than at the thalamic level. These observations show that cortical and thalamic projections to the frontal eye fields and posterior parietal cortex do not represent axonal collaterals of single neurons but originate from two distinct and partially overlapping populations of neurons. PMID- 8442708 TI - Deprenyl in attention deficit associated with Tourette's syndrome. AB - While central nervous system stimulants usually improve attention deficit hyperactivity disorder (ADHD) associated with Tourette's syndrome, they often exacerbate tics and can produce other potentially serious complications. Because deprenyl may have a stimulatory effect and monoamine oxidase inhibitors have been shown to ameliorate hyperactive behavior, we studied this drug in children with the Tourette's syndrome-ADHD combination. Twenty-nine patients, 25 boys and four girls, with a mean age of 11.2 years (range, 6 to 18 years) and duration of symptoms for an average of 6.2 years (range, 1 to 13 years), were enrolled in this open trial after they became refractory to conventional treatments for ADHD. The average duration of treatment with deprenyl was 6.7 months (range, 3 to 15 months) and the average daily dose was 8.1 mg/d (range, 5 to 15 mg/dL). Twenty six of all patients (90%) reported clinically meaningful improvement in their ADHD (score > or = 2 on a scale of 0 to 4), with the mean global improvement rated at 2.6. There were no serious adverse side effects and only two patients noted exacerbation of their tics. Deprenyl appears to be a safe and effective treatment of ADHD in patients with Tourette's syndrome. PMID- 8442709 TI - Comparison of scalp electroencephalogram with subdural electrocorticogram recordings and functional mapping in frontal lobe epilepsy. AB - We compared the findings of scalp electroencephalogram with subdural electrode array (SEA) recordings in 19 patients with refractory frontal lobe epilepsy. Prolonged scalp interictal recordings localized the epileptogenic zone in 12 patients; seven had no interictal sharp waves. The SEAs showed multifocal interictal sharp waves in all patients. Seven patients with localized seizure onset on scalp recording showed extensive ictal onset on the SEA recording. Five patients with lateralized seizure onset to one hemisphere on scalp recording were found to have ictal onset on SEA restricted to a smaller area. Because of the large epileptogenic zone found on SEA recordings, a complete resection was possible in only five (33%) of the 15 patients who had resections. Eight (53%) of the 15 patients benefited from surgery (mean follow-up, 4.6 years). The SEAs also allowed functional localization in most patients. From these data, we suggest that a localizing scalp electroencephalogram in patients with frontal lobe epilepsy may be misleading because SEA recordings show larger epileptogenic zones than anticipated. Furthermore, we postulate that the larger extensive epileptogenic zone may account for the poorer surgical outcome in patients with frontal lobe epilepsy compared with patients with temporal lobe epilepsy. PMID- 8442710 TI - Information processing efficiency in chronic fatigue syndrome and multiple sclerosis. AB - OBJECTIVE: To compare the cognitive performance of subjects with chronic fatigue syndrome (CFS), multiple sclerosis (MS), and healthy controls. All subjects were matched for age, education, and verbal intelligence, as previous neuropsychological studies of CFS had not used appropriate control groups. DESIGN: Case-control design. All subjects were given a neuropsychological battery and the test scores were compared among the groups. SETTING: Subjects with CFS and subjects with MS were recruited from private and institutional practice and from the community. Healthy subjects were recruited from the community. PATIENTS/OTHER PARTICIPANTS: Twelve subjects (all female) with CFS participated in the study. Chronic fatigue syndrome was diagnosed in these patients in accordance with the requirements outlined by the Centers for Disease Control as modified subsequently to not exclude patients with concurrent depression and/or anxiety. All subjects with CFS were referred for a neuropsychological examination to assess persistent cognitive complaints. Eleven subjects (10 female, one male) with the diagnosis of clinically stable MS were chosen from clinics and the community because of complaints of mild to moderate cognitive impairment. The subjects with MS and 11 healthy volunteers (10 female, one male) were matched to the group with CFS by age, education, and estimated verbal intelligence (based on the Vocabulary subtest of the Wechsler Adult Intelligence Scale-Revised). The subjects with MS had a mean Kurtzke Expanded Disability Status Scale score of 4.95 (SD, 1.95; range, 2.0 to 7.5). As a result of the matching procedure, there were no differences among the three groups in age (F[2,31] = 0.32), education (F[2,31] = 0.80), and verbal intelligence (F[2,31] = 0.31). INTERVENTIONS: None. MAIN OUTCOME MEASURES: These measures included the Beck Depression Inventory (BDI), the Paced Auditory Serial Addition Test (PASAT), Digit Span Test, and the Similarities Test of Verbal Abstract Reasoning. RESULTS: The mean number of correctly identified responses collapsed across the four PASAT trials was significantly different across groups (F[2,31] = 4.03; P < .05). While the CFS and MS groups did not differ from each other, subjects with CFS (SEM, 124.2 +/- 6.4) and subjects with MS (SEM, 112.9 +/- 10.9) scored significantly below controls (SEM, 146.4 +/- 6.4) (Fisher's Protected Least Significant Difference test; P < .05). There were significant differences among the three groups on mean Digit Span Test performance (F[2,31] = 5.5; P < .01). While the CFS and MS group did not differ significantly from each other, only the CFS group was significantly lower than control (Fisher's Protected Least Significant Difference test; P < .05). Mean performance on the Similarities test did not differ among the three groups (F = 0.58). In addition, there were significant differences among the three groups in mean BDI scores (F[2,31] = 7.6; P < .01). The CFS and MS groups did not differ significantly from each other, and both groups showed a statistically significantly elevated mean BDI score relative to the control group (Fisher's Protected Least Significant Difference test; P < .05). No significant correlations were found between BDI scores and PASAT total scores (CFS, r = -.21; MS, r = .13; control, r = .27), or between BDI and Digit Span Test (CFS, r = .32; MS, r = -.40; control, r = -.19). Results of the PASAT and Digit Span Test were significantly correlated in the CFS group (r = .71; P < .01), but not in the MS (r = .06) or control groups (r = .49). CONCLUSIONS: These results indicate that subjects with CSF and subjects with MS show significant impairment on a test of complex concentration when compared with appropriate controls. The data suggest that subjects with CFS and subjects with MS have difficulty on tasks that require the simultaneous processing of complex cognitive information. Selective impairment in information processing efficiency may lie at the PMID- 8442711 TI - Temporal lobe atrophy on magnetic resonance imaging in the diagnosis of early Alzheimer's disease. AB - OBJECTIVE: To evaluate the use of simple ratings and linear measures of atrophy in the temporal lobe structures obtained with magnetic resonance imaging coronal scans in the diagnosis of early Alzheimer's disease. DESIGN: Prospective series. The National Institute for Neurological Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for probable Alzheimer's disease. Blinded assessment. SETTING: Dementia study in a university hospital. SUBJECTS: Patients with Alzheimer's disease (n = 34), scoring 150 or more on the Extended Scale for Dementia, and age-matched healthy community volunteers (n = 39) who had both magnetic resonance imaging coronal scans and a psychometric assessment using the Extended Scale for Dementia within 6 months were included. MEASURES: MAIN MEASURES: T1-weighted magnetic resonance imaging coronal scans, a 1.5-T system. The degree of atrophy rated (0 to 4) in both sides of the temporal neocortex, entorhinal cortex, hippocampal formation, temporal horns, third ventricle, lateral ventricles, and frontal and parietal cortex. Linear measures: the area of hippocampus and the maximal transverse width of temporal horns. RESULTS: Differentiation between patients with Alzheimer's disease and controls was limited by considerable variations in sensitivity and specificity. Receiver operating characteristics analysis revealed a clear order of discrimination, the entorhinal cortex and the temporal neocortex being the two best, followed by the temporal horns and hippocampal formation. For a given specificity of 90%, the corresponding sensitivity for the entorhinal cortex, temporal neocortex, temporal horns, and hippocampal formation was 95%, 63%, 56%, and 41%, respectively. Linear measures differed significantly but showed considerable overlap. CONCLUSION: The presence of rated atrophy in selected temporal structures makes the diagnosis of Alzheimer's disease more likely, but the absence does not rule out the possibility of early Alzheimer's disease. PMID- 8442712 TI - The practice of neurology in Thailand. A different type of medical specialist. AB - A survey of 1700 patient encounters during 1 week of practice by 23 neurologists in Thailand delineates a different scope of specialty practice compared with that of many Western nations. Thai neurologists had an average of 96 patient encounters per week of practice, with two thirds of all encounters in ambulatory care. However, one half of all encounters were for self-referred patients, three fourths of all encounters were regular patients for whom the neurologist provided continuing care, and about one half of all encounters were thought to reflect health problems that fall within the scope of general internal medicine. The data suggest that Thai neurologists function in health care delivery as general internists with special competencies and interests in the field of neurology. This balanced style of specialist practice serves to reinforce the primary care infrastructure of the health system in developing countries. PMID- 8442713 TI - William P. Letchworth: philanthropist and pioneer epileptologist. AB - Although neither a physician nor a scientist, William Pryor Letchworth significantly improved the care and treatment of epileptics at the beginning of this century. As commissioner of the New York State Board of Charities and later president, he established Craig Colony, America's first comprehensive epilepsy facility. In Care and Treatment of Epileptics, he summarized contemporary medical and social knowledge of epilepsy. As cofounder and president of the National Association for the Study of Epilepsy, he introduced from Europe his improvements of the colony plan of construction and financed Transactions, the society's scholarly journal. He combined a sensitivity to the needs of the unfortunate with the resolve of a successful businessman. Although William Pryor Letchworth is remembered for his philanthropy and the park in western New York that bears his name, his signal contributions to modern concepts of epilepsy are unknown to most physicians. This article will acquaint readers with the life and accomplishments of this philanthropist and pioneer epileptologist. PMID- 8442714 TI - Fatal rabies associated with extensive demyelination. AB - OBJECTIVE: To compare the clinical course with the neuropathological findings in a patient who died of acute rabies encephalomyelitis with coexisting demyelinating lesions. DESIGN: Patient's history was extensively investigated, during her illness and after death. Details of her previous allergies, postexposure prophylaxis, early use of steroid therapy, 20-day course in an intensive care unit, and autopsy results are clinicopathologically correlated. SETTING: The intensive care unit of an 1100-bed tertiary referral center and teaching hospital. PATIENT: A 55-year-old woman, referred by her family doctor. CONCLUSIONS: Postvaccinal encephalomyelitis and rabies can run similar courses and can be misdiagnosed. On admission to the hospital, this patient was initially diagnosed as having postvaccinal disease. However, autopsy results and postmortem viral cultures disclosed a complex picture, including acute rabies and widespread perivenous demyelination. One other similar report from 1977 in the literature is reviewed. No adequate explanation of the rare coexistence of acute rabies encephalomyelitis and perivascular demyelination is available. PMID- 8442716 TI - The structure of dentine after the injection of strontium chloride by backscattered electron imaging in the scanning electron microscope. AB - The subcutaneous injection of 0.5 ml of 20% aqueous strontium chloride produced a distinct calciotraumatic response in rat incisor dentine. In both the labial and lingual dentine this consisted of an unmineralized layer comprising continuous interglobular spaces. Lingually this unmineralized layer was sharply defined and about 1-2 microns in width but labially it was more irregular, diffuse and difficult to measure. Labially and lingually the dentine formed after the unmineralized layer hypomineralized in comparison to the rest of the dentine. Within the hypomineralized labial dentine a diffuse, more intensely hypomineralized layer was often present. The appearance of the unmineralized layer probably reflects the differences in structure between labial and lingual dentine, that is, small linear calcospherites lingually and large irregular calcospherites labially. PMID- 8442715 TI - Defective aldosterone synthesis associated with hyperkalemic periodic paralysis. AB - OBJECTIVE: To describe defective aldosterone biosynthesis (corticosterone methyl oxidase type II [CMO-II] deficiency) in a kindred with hyperkalemic periodic paralysis. SETTING: Tertiary care hospital in Madison, Wis. PATIENTS: Individuals studied included a female infant with failure to thrive, hyponatremia, and hyperkalemia; the infant's asymptomatic mother and father; and a maternal aunt and grandmother with hyperkalemic periodic paralysis. INTERVENTIONS: Mineralocorticoid synthetic pathways were analyzed with synthetic adrenocorticotropin stimulation. In one patient with hyperkalemic periodic paralysis, acetazolamide sodium therapy was discontinued and replaced with fludrocortisone acetate therapy. MEASUREMENTS/MAIN RESULTS: Impaired aldosterone synthesis with marked accumulation of mineralocorticoid precursors 18 hydroxycorticosterone and corticosterone indicated severe CMO-II deficiency in the infant. In her relatives and parents, baseline aldosterone levels (74 to 111 pmol/L) were low (reference range, 194 to 830 pmol/L, a nonstricted sodium diet). Serum 18-hydroxycorticosterone levels (442 to 1021 pmol/L) were normal (reference range, 138 to 1270 pmol/L), but ratios of 18-hydroxycorticosterone to aldosterone were abnormally elevated (4.5 to 13.7; reference range, 2.65 +/- 1.86), indicating deficient CMO-II enzyme activity. Acetazolamide therapy was substituted with fludrocortisone therapy in the maternal aunt without return of paralytic symptoms. CONCLUSION: This association of hyperkalemic periodic paralysis with CMO-II deficiency and resolution of paralytic episodes with fludrocortisone therapy suggests a contribution of defective mineralocorticoid mediated potassium homeostasis to the pathogenesis of hyperkalemic periodic paralysis. PMID- 8442717 TI - Characteristics of palatal wound healing in desalivated rats. AB - The healing of excisional wounds in the palate of desalivated rats was evaluated. Experimental rats became desalivated after extirpation of the submandibular and sublingual glands and ligation of the parotid ducts. Small or large circular wounds, 3 or 5 mm in diameter, were produced in the palate. The wound area, area of inflammation, area of connective tissue formation and the number of myofibroblasts were determined at 0, 3, 7, 14, 21 and 28 days after surgery. The area of the small wound (3 mm) was similar in experimental and control groups; however, the area of the large wound (5 mm) was greater in the experimental group (p < 0.05-0.01). The area of inflammation was greater in the experimental group with small or large wounds (p < 0.05-0.01). Connective tissue formation was less (p < 0.01) in desalivated rats with a small wound at day 14 and with a large wound at days 21 and 28. There were fewer myofibroblasts in the large wound of desalivated rats (p < 0.01) than in controls between days 3 and 14. The results indicate that palatal wound healing is delayed in desalivated rats and that larger wounds are more sensitive to desalivation than smaller wounds. PMID- 8442718 TI - Immunohistochemical detection of prostaglandin I2 synthase in various calcified tissue-forming cells in rat. AB - Localization of prostaglandin (PG) I2 synthase immunoreactivity was examined in demineralized sections of rat pulpal, periodontal and skeletal tissues using isn 1, a monoclonal antibody raised against the enzyme. Various calcified tissue forming cells, i.e. odontoblasts, osteoblasts, osteocytes, cementoblasts, cementocytes and chondrocytes, were similarly immunoreactive for PGI2 synthase, suggesting that they are capable of producing PGI2. In odontoblasts and chondrocytes, the reactivity increased gradually with maturation. Weak immunoreactivity was also observed in endothelial cells and fibroblast-like cells in pulpal and periodontal tissues. However, no reactivity was seen in ameloblasts. These results suggest the possible involvement of PGI2 in the regulation of the metabolism of various calcified tissues. Monoclonal antibodies such as isn-1 may become useful markers of the maturation of calcified tissue forming cells of mesenchymal origin. PMID- 8442719 TI - The presence of vesicles containing lactate dehydrogenase in the ameloblast layer of bovine enamel organ. AB - Ameloblast layers were removed from bovine enamel organs, followed by the separation of the extracellular matrix-vesicle fraction after collagenase digestion. Lactate dehydrogenase (LDH)-containing vesicles were found in that fraction. LDH in these vesicles did not result from cell lysis and vesicle capture during the preparation of the fraction. The isoenzyme pattern of LDH in LDH-containing vesicles was similar to that of cytosolic LDH of ameloblasts, suggesting the presence of a mechanism for specific uptake of cytosolic LDH during the in vivo formation of the vesicles. The existence of LDH-containing vesicles in enamel organ, where mineralization had been believed not to be initiated by matrix vesicles, suggests the possibility that LDH-containing vesicles have a specific function different from that of matrix vesicles. PMID- 8442720 TI - Initiation of secondary cartilage in the mandible of the Syrian hamster in the absence of muscle function. AB - The functioning lower jaw is a prerequisite of the ongoing secondary chondrogenesis in the mammalian mandibular condyle. Does the articular function also initiate secondary chondrogenesis in the mandible? The angular process of the fetal mammalian mandible possesses a large secondary cartilage without any apparent articular function. Past studies have shown that the anlage of the lower jaw of the mouse embryo grown in organ culture produces condylar and angular cartilages as in vivo. In order to clarify further the capacity of the mandibular anlage to initiate secondary chondrogenesis in a non-functional environment, mandibular arch explants taken from the prenatal hamster before any cartilage or bone formation was apparent were grown in organ culture. Both primary and secondary cartilage could be found in them within 9-10 days. The results thus indicate that initiation of the condylar and/or angular secondary cartilaginous development in the rodent mandible occurs in the absence of jaw-opening function, although the pertinent literature indicates that function maintains cartilaginous differentiation in the condyle. PMID- 8442721 TI - Interleukin-1 beta and IgG subclass concentrations in gingival crevicular fluid from patients with adult periodontitis. AB - Interleukin-1 beta (IL-1 beta) and the four IgG subclasses were measured in gingival crevicular fluid (GCF) at 35 sites in 19 patients with adult periodontitis. Serum concentrations of the IgG subclasses were assayed in 16 patients. IL-1 beta was detected in GCF at 88.6% of sites at concentrations ranging from 12.38-420.90 pg/microliters (mean 138.35 +/- 112.61 pg/microliters). IgG1 was detected at 81.2% sites, IgG2 at 93.6%, IgG3 at 71% and IgG4 at 71%. Absolute concentrations in GCF were: IgG1--2.419 g/l +/- (SD) 3.389; IgG2--2.945 +/- 6.434; IgG3--0.118 +/- 0.144; IgG4 0.864 +/- 1.336. There were no significant correlations between IL-1 beta concentrations, GCF volume or the clinical status of the sample site. IL-1 beta was not correlated with any of the IgG subclasses. The absolute concentrations of all subclasses in GCF were significantly negatively correlated with GCF volume and positively correlated with the Bleeding Index. Only IgG4 was significantly negatively correlated with the probeable crevice depth index. The concentration of each IgG subclass was positively correlated with the other three IgG subclasses. Subclass concentrations in GCF, relative to serum concentrations, were not correlated with GCF volume or clinical status. Relative concentrations of IgG1, IgG2 and IgG3 showed significant positive correlation with each absolute concentration of the other subclasses but IgG4 did not show this relation. It was concluded that IL-1 beta is not related to clinical measurements of inflammation or previous attachment loss. The data suggest that IgG in GCF is largely derived from plasma but that some IgG4 may be locally synthesized. PMID- 8442722 TI - The effect of conditioned medium from connective tissue fibroblasts and epithelium on calcium release from mouse calvarial organ culture. AB - Fibroblasts from periodontal ligament and gingival explants were cultured in vitro. The conditioned media from four different periodontal ligament and four gingival explant cultures were examined to determine their effect on calcium release in mouse calvarial organ culture. All the cultures stimulated calcium release, with a range of 20.6-43% over control. Conditioned media from two periodontal ligament cultures and a gingival culture significantly stimulated calcium release from the bone organ culture. The stimulatory activity in the oral fibroblasts cell cultures was compared to that in conditioned medium from two non oral, established, fibroblasts cell lines and an epidermal keratinocyte cell line. Similar to the oral fibroblast cultures, conditioned medium from all three cell lines resulted in stimulation of calcium release in the bone culture assay. In order to characterize the bone-stimulating activity, a 0.4 micron membrane was used to separate the cell cultures from the bone organ culture. Both gingival and periodontal ligament fibroblast cultures gave values for calcium release significantly less than control when the separating membrane was used. Both non oral cell lines and the epidermal keratinocyte cell line gave values for calcium release similar to those when no membrane was used. These results suggest that oral fibroblasts, but not non-oral fibroblasts and epidermal keratinocytes, release a unique bone-resorption stimulating activity. PMID- 8442723 TI - Autoradiographic study of the effects of pulsed electromagnetic fields on bone and cartilage growth in juvenile rats. AB - Application of pulsed electromagnetic fields (PEMF) has been used in growth and repair of non-union bone fractures. The similarities between the fibrocartilage callus in non-union bone fractures and the secondary cartilage in the mandibular condyle, both histologically and functionally, lead naturally to study the effects of PEMFs on growth in the condyle. The purposes of this study were: (1) to describe the effects of PEMFs on the growth of the condyle using autoradiography, [3H]-proline and [3H]-thymidine, and (2) to differentiate between the effects of the magnetic and electrical components of the field. Male pre-adolescent Sprague-Dawley rats (28 days old) were divided into three experimental groups of five animals each: (1) PEMF-magnetic (M), (2) PEMF electrical (E) and (3) control, and were examined at three different times-3, 7 and 14 days of exposure. Each animal was exposed to the field for 8 h per day. Histological coronal sections were processed for quantitative autoradiography to determine the mitotic activity of the condylar cartilage and the amount of bone deposition. The PEMF (magnetic or electrical) had statistically significant effects only on the thickness of the articular zone, with the thickness in the PEMF-M group being the most reduced. Length of treatment was associated with predictable significant changes in the thickness of the condylar cartilage zones and the amount of bone deposition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8442724 TI - Neutrophil dysfunction in rats with natural gingivitis. AB - The functions of polymorphonuclear neutrophils (PMN) from SUS rats with naturally occurring gingivitis were examined by the luminol-dependent chemiluminescence (CL), adherence and bactericidal tests. SUS rats with pre-gingivitis showed lower CL responses of isolated PMNs and whole blood than control rats (RES rats). After plague formation and progression of gingivitis, the CL response gradually increased in SUS rats. RES rats had healthy gingiva and showed no increase in CL responses. Impaired PMN adherence was observed in SUS rats with pre-gingivitis but not in RES rats. PMNs from SUS rats with pre-gingivitis also showed lower bactericidal activity than those from RES rats. Dysfunction of PMNs might induce gingivitis as a result of decreased protection against periodontal pathogens and an elevated level of CL response can be recognized with progression of gingivitis. PMID- 8442725 TI - The effect of sympathectomy on the occurrence of microliths in salivary glands of cat as studied by light and electron microscopy. AB - Parasympathectomy is followed by a greatly increased occurrence of microliths in the feline submandibular gland, which appears to be because of secretory inactivity. The sympathetic nerves are also important in secretory processes, and so feline submandibular, sublingual and parotid glands subjected to postganglionic sympathectomy for periods from 1 day to 1 yr have now been investigated. Microliths were detected in two out of 28 sympathectomized submandibular glands and four out of 27 untreated glands, and in 10 out of 22 sympathectomized sublingual glands and seven out of 19 untreated glands. There were no significant differences between the occurrence of microliths in sympathectomized and untreated glands. Microliths were not detected in any of 29 sympathectomized and 30 untreated parotid glands. The appearance of the sympathectomized glands was similar to that of the untreated glands. The failure of sympathectomy to affect the occurrence of microliths or the appearance of the glands is possibly because of parasympathetic nerve impulses, which produce continuing secretory activity, and also the spontaneous secretion of the sublingual gland. The results support the concept that secretory inactivity is an aetiological factor of microlithiasis. PMID- 8442726 TI - The sequence of eruption of the permanent dentition in a Chilean sample with Down's syndrome. AB - The eruption of the permanent teeth in Down's individuals is reportedly delayed. The extent of such delay in comparison to normal children has been little studied. The eruption characteristics of the permanent teeth in a sample of Chilean individuals with Down's syndrome were here compared with those of the normal Chilean population. The sample consisted of 240 Down's individuals (all with trisomy 21), 116 males and 124 females. The chronological sequence of eruption in Down's children was not completely different from the normal. The least affected teeth were upper and lower first molars and central and lateral incisors. Alterations of the eruption sequence were not necessarily a consequence of alterations in the time of eruption. Asymmetries between sides of the jaw were mainly in canines and premolars. Alterations in sequence timing and asymmetry seem to be age dependent, being less frequent between 7 and 9 yr of age and more frequent between 10 and 14 yr of age. This may also reflect the larger variances of age of eruption observed in Down's individuals. Despite this, Down's children maintained a certain similarity in sequence and symmetry in comparison to normals. PMID- 8442727 TI - Ultrastructural quantification of collagen in the articular disc of the temporomandibular joint of the rabbit. AB - Collagen fibril diameters were quantified in two regions of the articular disc of this joint. One region was the thinner, translucent central part of the disc; the other was from the thicker, opaque peripheral part more anteriorly. Mean collagen fibril diameters in the thicker zone were small and had a unimodal distribution. In contrast, mean collagen fibril diameters in the thinner central region were larger and with a much wider range of values, as indicated by the larger standard deviations. It was concluded that regional variations exist in the collagen of the rabbit articular disc and may reflect the mechanical loads to which the disc is subjected. PMID- 8442728 TI - Changes in dimensions and weight of human dentine after different drying procedures and during subsequent rehydration. AB - Shrinkage of dentine and the decrease in its weight after drying were measured. Three drying procedures were used, freeze-drying and drying in nitrogen at 60 and 100 degrees C. The dentine was subsequently rehydrated while measuring its dimensions. Rehydrated dentine was weighed. Dentine weight decreased by 10.2, 9.0 and 10.5% with the three different drying procedures. Shrinkage was about equal with all three methods. Linear dimensional changes were 1.7-2.0% in the plane perpendicular to the tubules and 1.4-1.7% in the direction of the tubules. During rehydration, freeze-dried dentine and dentine dried at 60 degrees C regained its original wet dimensions and weight. Dentine dried at 100 degrees C showed some permanent shrinkage and weight loss. PMID- 8442729 TI - The action of scopolamine on retrieval and memory storage in rats evaluated in the staircase maze. AB - Rats were trained to run on staircase stopping on the 3rd, 6th, 9th, and 12th steps (correct responses). Stopping on any other step was considered an error. The acute administration of scopolamine (1.5 mg/kg) 20 min before the trial caused a reduction of the correct responses. An interruption of the daily training for 20 days caused, in the controls, a 24% reduction of correct responses. A chronic administration of scopolamine, at doses over 10 mg/kg in the first 15 days of the no-training period, nullified the behavioral deterioration observed in the controls. The interpretation of these results is that scopolamine damages the retrieval process and blocks the spontaneous decay of memory, as was observed in the controls after 20 days of interruption of the daily training. PMID- 8442730 TI - Adrenalectomy attenuates the improvement of memory in rats by peripheral application of Des-Tyr-D-Pro4-casomorphin. AB - beta-Casomorphin derivatives without the N-terminal amino acid tyrosine possess memory-improving effects after central and peripheral application. We investigated the significance of adrenal glands for the memory improving effect of the systemically applied beta-casomorphin derivative des-Tyr-D-Pro4CM (Pro-Phe D-Pro-Gly) in a learning experiment. Seven-week-old rats were adrenalectomized or sham operated. One week after surgery the rats were trained in an active avoidance task in a shuttle box. Five avoidance reactions were taken as learning criterion. After training 10 nmol/kg des-Tyr-D-Pro4CM or saline (10 ml/kg) was subcutaneously applied. There were no differences in acquisition between adrenalectomized and sham-operated rats. The memory retention of sham-operated animals was improved by des-Tyr-D-Pro4CM. In adrenalectomized rats this positive effect could not be observed. The involvement of adrenal glands in the peptide effect during learning and retention is discussed. PMID- 8442731 TI - Effect of changes in the intrahippocampal vasopressin on memory retrieval and relearning. AB - Previous results have indicated the involvement of the hippocampus in the behavioral effect of vasopressin, with a better effect when the peptide was injected in the ventral part rather than in the dorsal part of this structure. The purpose of the present study was to determine, in mice, whether the injection of vasopressin or vasopressin antisera into the ventral hippocampus has an effect on retrieval and relearning of a Go-No Go visual discrimination task and, if so, to what extent this involvement of the vasopressin system depends on the integrity of the medial amygdaloid nucleus, the main source of vasopressin innervation in the ventral hippocampus in rats. In the first experiment, we showed that pretest microinjection of Arg8-vasopressin (25 pg per animal) in the ventral hippocampus alleviated forgetting observed after a prolonged interval of 24 days between the acquisition of information and its retrieval. This enhancing effect was characterized by better retrieval and relearning in vasopressin treated mice than those in control mice. Conversely, an immunoneutralization of endogenous vasopressin in the ventral hippocampus by the microinjection of vasopressin antisera (1/10 dilution) resulted in the drastic impairment of retrieval and relearning. Since the lack of an observable change in a locomotor activity test might explain these results, we postulated that the vasopressin system in the ventral hippocampus is involved in retrieval processes. Moreover, the effects of these treatments in a nonassociative context suggest that the effect of vasopressin could be dependent on the contextual paradigm used. In the second experiment, we localized vasopressin immunoreactive fibers in the CA1-CA2 ventral hippocampal fields and CA4-gyrus dentatus region, and vasopressin perikarya in the medial amygdaloid nucleus. Then, the projection of vasopressin cells from the medial amygdaloid nucleus to the ventral hippocampus was evaluated by studying changes in vasopressin immunoreactive fiber density in the ventral hippocampus after a lesion of the medial amygdaloid nucleus. The results showed the almost complete disappearance of vasopressin fibers in the CA1-CA2 hippocampal fields after the medial amygdaloid lesion. In contrast, vasopressin fibers in the CA4 and gyrus dentatus region remain unchanged. On the basis of our immunohistochemical results, our third experiment tested the repercussions of the change in vasopressin innervation in the ventral hippocampus, due to the medial amygdaloid lesion, on the effects of exogenously administered vasopressin on both retrieval and relearning processes. The medial amygdaloid lesion induced a deleterious effect on retrieval without really affecting the ability to relearn. No observable change in locomotor activity could explain this impairment.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8442732 TI - Taste memory: the role of protein synthesis in gustatory cortex. AB - Application of the protein synthesis inhibitor anisomycin to the rat gustatory cortex before and during training impairs conditioned taste aversion (CTA) to saccharin. No behavioral impairment is observed if the inhibitor is applied to an adjacent cortical area or to one cortical hemisphere only. The consumption of saccharin and of total fluid, as well as behavioral recognition of saccharin, is not affected. Preexposure of rats to saccharin several days before training markedly inhibits CTA to that taste. Injection of anisomycin to the gustatory cortex immediately prior to the preexposure period attenuates the latent inhibition. These results suggest that protein synthesis in the gustatory cortex is required for normal acquisition of the memory of taste. PMID- 8442733 TI - Nicotinic receptor agonists facilitate retention of avoidance training: participation of dopaminergic mechanisms. AB - The effect of nicotinic receptor agonists on retention of the inhibitory avoidance (IA) response were investigated in mice. Animals received intraperitoneal drug injections before training, and retention was evaluated 24 h later. Nicotine and cytisine, but not lobeline, significantly increased retention of the IA training. Cotinine, the main metabolite of nicotine, was inactive in the same test. Retention was not affected by the injection of the D1-D2 receptor antagonist cis-flupentixol, but the preadministration of cis-flupentixol significantly blocked the facilitatory effect of nicotine and cytisine on memory. These results demonstrate that the nicotinic receptor agonists nicotine and cytisine facilitate the retention of avoidance responses and suggest that this effect is mediated through central dopaminergic pathways. PMID- 8442734 TI - Social transmission of flavored tea preferences: facilitation by a vasopressin analog and oxytocin. AB - Social transmission of information was tested in a procedure in which a rat (Observer) could demonstrate preference for a flavored tea as drinking solution that a con-specific (Demonstrator) had consumed just prior to a period of social interaction between the two animals. The cue in this procedure, probably olfactory in nature, was remembered for a relatively short period of time. It was prolonged when the Observers were treated with dresglycinamide[Arg8]-vasopressin (DGAVP) or oxytocin immediately after the encounter with the Demonstrator. DGAVP was effective after the injection of 15 micrograms.kg-1 but not of 1.5 ng.kg-1. Oxytocin induced the effect in doses ranging from 1.5 ng.kg-1 to 15 micrograms.kg 1. A dose of 0.15 ng.kg-1 was inactive. The influence of the peptides was cue specific. It is concluded that DGAVP and oxytocin facilitate social transmission of information, as previously found for social recognition. PMID- 8442735 TI - Medullary afferent vagal axotomy disrupts NaCl-induced short-term taste aversion learning. AB - The effect of medullary afferent vagal axotomy on NaCl-induced short-term and long-term taste aversion learning (TAL) was examined to assess the relevance of the vagus nerve in drug-induced TAL. The results show that medullary afferent vagal axotomy disrupts NaCl-induced short-term (nondelayed) TAL, while having no effect on learning acquired with the same product in long-term (delayed) TAL protocols. Acquisition of learning in delayed discrimination tasks may be mediated by alternative mechanisms of nonvagal nature, e.g., the humoral system. The possibility that short-term and long-term TAL may be mediated by different neurobiological substrates is discussed. PMID- 8442736 TI - Do vocalizations of the male rat elicit calling from the female? AB - Female rats emit calls during copulation that appear to be associated with their own proceptive behavior. In an earlier study, we had determined that females emit calls when presented with odor cues from a sexually competent adult male. Two experiments were undertaken to determine whether females would vocalize when presented with tape recorded male ultrasonic vocalizations. In the first females were presented with no calls, male mating calls or male preejaculatory calls. They received one test in each sound condition with a devocalized male in the immediate vicinity and one test with no male present. Females tested alone called at a lower level than those tested in the presence of a devocalized male. The presence of male calls did not significantly increase the frequency of calling in females tested in the presence of a male. When females were tested alone, however, calling did increase significantly when male mating calls were presented, but not when preejaculatory calls were presented. In a second experiment, it was confirmed that male mating vocalizations elicited more calls from the female. Thus, male mating calls may elicit vocalizations from the female, but are less effective than male odor cues. PMID- 8442737 TI - Long-term maintenance of song in adult zebra finches is not affected by lesions of a forebrain region involved in song learning. AB - The long-term maintenance of stable song patterns produced by adult male zebra finches depends upon auditory feedback. It is not known which song-related brain areas process this auditory information, in part because previous functional studies in adult birds have not been of sufficient duration to detect behavioral changes that might result from interference with auditory feedback mechanisms. In the present study, adult males were subjected to bilateral lesions of a nucleus known to be necessary for auditory-based song learning, the lateral portion of the magnocellular nucleus of the anterior neostriatum (IMAN). Songs were then recorded over a period of time during which deficits due to removal of auditory feedback become apparent. Our data suggest that the IMAN does not mediate the stabilizing influence of auditory feedback on adult song production. That is, while deafening produces alterations in song structure within 16 weeks, bilateral destruction of the IMAN did not produce any substantial changes in song over this same period. These results extend a previous report by Bottjer, Miesner, and Arnold, Science, 224, 901-903 (1985) and suggest that the pathways through which auditory feedback affects adult song behavior do not involve the IMAN. PMID- 8442738 TI - Effects of lateralized US and CS presentations on conditioned head turning and bilateral cingulate cortex responses in cats. AB - A lateralized tone conditioned stimulus (CS+) paired with a rewarding medial forebrain bundle (MFB) stimulation unconditioned stimulus (US) was presented to one ear of the cat, while the same tone was presented to the other ear alone (CS ). Specifically, the electrical stimulation of the MFB elicited a contralateral head turn as the unconditioned response (UR). Correspondingly, the CS+ was given to an ear contralateral to the direction of the UR. During the CS test session the cats oriented toward the tones, but these head movements habituated rapidly. During conditioning the cats developed stereotypical extended vigorous head turns to the CS+, with significantly greater acceleration and shorter onset latencies to the CS+ than to the CS-. Head turns in response to the CS+ were always ipsilateral to the tone, but responses to the CS- were in some cats ipsilateral and in most cats contralateral to the tone. Recordings of the slow potential responses showed a broad negative deflection in the cingulate cortex, with peaks at 140 and 250 ms. The amplitude of this negative potential to the CS+ was larger than that to the CS-, but no asymmetries were found between the hemispheres. The present behavioral paradigm is potentially useful for studying the neural basis of conditioned approach responses. PMID- 8442739 TI - The fear of fear concept: stability, retest artefact and predictive power. AB - Three related issues concerning the theory, measurement and clinical utility of the fear of fear construct as operationalized by the Agoraphobic Cognitions and Bodily Sensations Questionnaires (Chambless, Caputo, Bright & Gallagher, Journal of Consulting and Clinical Psychology, 52, 1090-1097, 1984) were addressed: stability of ranked scores, stability of means (retest effect) and predictive ability. In addition to measures assessing moods and enduring personality traits, the relevant fear of fear scales (and introducing a companion frequency measure to the BSQ-intensity scale) were administered to somewhat over 60 clients with "panic disorder with agoraphobia" or "agoraphobia without a history of panic attacks" on two occasions, 3 months apart, with no intervention having taken place between first and second testing. As predicted, ranked fear of fear scores were highly stable. In addition, Howarth's mu index values pointed to the description of the fear of fear constructs in terms of traits. Specific fear of fear scales showed evidence of a retest effect. The short-term course of agoraphobic avoidance behaviour in untreated cases was predictable from specific fear of fear variables, even after controlling for their shared variance with pre test measures of either state anxiety-panic or trait neuroticism. Implications of the findings are discussed. PMID- 8442740 TI - Obsessions, responsibility and guilt. AB - Introduction of the concept of "inflated responsibility" into the so-called anatomy of obsessions gives rise to an elaborated analysis of obsessions, responsibility and guilt. The analysis touches on a range of phenomena including anger and guilt, control of thoughts, the fusion of thoughts and action, resistance to additional responsibility, procrastination and unfinished tasks, hypochondriasis, brief holidays. Some clinical implications are deduced from the analysis. PMID- 8442741 TI - Can the Yale-Brown Obsessive Compulsive Scale be used to assess trichotillomania? A preliminary report. AB - Given recent conceptualizations of trichotillomania (TM) as a variant of obsessive compulsive disorder (OCD), clinician-rated measures of obsessive compulsive symptoms have been adapted for use in the assessment of TM. Although the reliability and validity of these instruments have been well-documented in patients with OCD, psychometric properties have not been examined systematically in patients with TM. Here, we evaluate the reliability and validity of the Yale Brown Obsessive Compulsive Scale (Y-BOCS) in a sample of 11 patients with a primary diagnosis of TM. Data addressed the utility of the Y-BOCS for evaluating symptoms of TM, and provided information regarding the proposed overlap between OCD and TM. Initial analyses suggested that interrater reliability, internal consistency, and test-retest reliability for the total score were adequate. However, the range of scores was somewhat restricted, and suggested in particular that interference in daily functioning from TM symptoms is quite low. Both internal consistency and test-retest reliability for the Target Behaviors subscale were inadequate, suggesting that this combined score is inappropriate for use with TM patients. Concurrent validity data using the total score were mixed, although the Y-BOCS did appear to be sensitive to change in TM symptoms over treatment. Implications for the use of the Y-BOCS with TM patients and hypothesized phenomenological differences between TM and OCD are discussed. PMID- 8442742 TI - Comparing high school and college students' leisure interests and stress ratings. AB - We compared a large high school area sample with normative data from prior research with college students on the Leisure Interests Checklist (LIC) factor scales, and on the BAROMAS. Whether combined or separated by sex, the college sample displayed far more interest in the LIC activities than the high school students (all P << 0.001). On the BAROMAS, differences were more complex. The teenagers expressed more confidence about dismissing time pressures, sleeping soundly and finding time to do sports, but college students were more confident about falling asleep and sticking to set priorities. The high school data replicated the previous pattern of LIC x BAROMAS relationships, with most scales significantly inter-correlated within inventories, but mainly the sports scales covarying across the two inventories. Numerous differences between the sexes emerged from the high school student sample. PMID- 8442743 TI - Appraisal of cognitive intrusions and response style: replication and extension. AB - In a replication and extension of an earlier study of cognitive intrusions, appraisal and response strategies (Freeston, Ladouceur, Thibodeau & Gagnon, Behaviour Research and Therapy, 29, 585-597, 1991a), cognitive intrusions were studied among 534 outpatients and escorts recruited in waiting rooms of two large urban hospitals. Appraisals of high probability and low disapproval were associated with greater use of continued attention strategies whereas appraisals of low probability and high disapproval were associated with greater use of escape/avoidance strategies. These results support the distinction between the ego-dystonic nature of obsessional intrusive thoughts and ego-syntonic concerns about subjectively probable events found in worry. PMID- 8442744 TI - Panic attacks and interoceptive acuity for cardiac sensations. AB - It has been suggested that perception of visceral changes, and cognitive reactions to such changes, may be important for triggering panic attacks. It remains to be determined, however, whether people with panic attacks are actually characterized by enhanced perceptual acuity for interoceptive stimuli. The purpose of this study was to explore the relationship between panic attacks and awareness for cardiac sensations using an objective heartbeat discrimination procedure. Twenty panickers and 20 nonpanickers were given 60 trials of the Whitehead heartbeat discrimination procedure. Thirty trials were given during rest and 30 following hyperventilation. Results indicated that panic attacks were not related to enhanced interoceptive acuity for cardiac sensations, either at rest or following hyperventilation. These results are discussed in terms of their relevance to cognitive models of panic. PMID- 8442745 TI - Anxiety sensitivity and its relationship to spontaneous and cued panic attacks in college students. AB - The present study was an attempt to clarify the relationship that exists between anxiety sensitivity and panic attacks. The Anxiety Sensitivity Index (ASI) and the Anxiety Questionnaire were administered to 463 college students to determine their levels of anxiety sensitivity and history of spontaneous and cued panic attacks. High anxiety sensitive Ss experienced more spontaneous panic attacks than the medium or low anxiety sensitive Ss. Additionally, high anxiety sensitive Ss reported more cued panic attacks than the medium or low anxiety sensitive Ss. These results suggest that both spontaneous and cued panic attacks may play a prominent role in the development of anxiety sensitivity. PMID- 8442746 TI - Negative affect, pain and disability in osteoarthritis patients: the mediating role of muscle weakness. AB - Negative affect has been shown to be associated with high levels of pain and disability in osteoarthritis (OA) patients. As an explanation of this association, it was hypothesized that muscle weakness is a mediating factor between negative affect, pain and disability. Accordingly, negative affect enhances the patient's tendency to avoid pain-related activities; a low activity level induces muscle weakness, instability of joints and thus pain and disability. This theory leads to the prediction that the association between negative affect, pain and disability is most pronounced in patients with weak muscles. The prediction was tested in a study on patients with OA of the hip and/or knee. Regarding disability (but not pain), the prediction was confirmed. This study indicates that muscle weakness is a mediating factor between negative affect and disability in OA-patients. PMID- 8442747 TI - A further experimental investigation of thought suppression. AB - It has often been suggested that attempts to suppress a thought will lead to an immediate and/or delayed increase in its occurrence. In a recent experiment (Clark, Ball & Pape, Behaviour Research and Therapy, 29, 253-257, 1991) we obtained a delayed (rebound) effect but failed to demonstrate an immediate enhancement effect. Lavey and van den Hout (Behavioural Psychotherapy, 18, 251 258, 1991) have suggested immediate enhancement might be observed only if subjects are instructed not to use distraction while suppressing. The present experiment tested this hypothesis. An immediate enhancement effect was not obtained but the delayed (rebound) effect was twice replicated and an artifactual explanation of this effect was discounted. PMID- 8442748 TI - Predicting outcome after treatment for generalised anxiety disorder. AB - A previous paper, Butler and Anastasiades (Behaviour Research and Therapy 26, 531 534, 1988) presented evidence for three reliable predictors of response to Anxiety Management in patients with generalised anxiety disorder. It was argued there that these reflected severity of anxiety, demoralisation and depression. A second study (Butler, Fennell, Robson & Gelder, Journal of Consulting and Clinical Psychology, 59, 167-175, 1991) has compared two treatments for GAD: Behaviour Therapy and Cognitive Behaviour Therapy. Data from this study is used here to answer two questions: (i) do the same three variables predict outcome in the second study? The answer to this question is 'no'; and (ii) which variables contribute to prediction of outcome when these two treatments are compared? Information presented here suggests that this depends partly on the nature of the treatment given. Outcome after behaviour therapy is predicted by initial levels of anxiety only, but the gains made are also relatively modest. Outcome after cognitive behaviour therapy is predicted by the degree to which ambiguous (external) information is interpreted as threatening. Thus a cognitive variable contributes reliably to the prediction of outcome after a cognitive treatment, but does not predict in the same way to outcome after a behavioural treatment. PMID- 8442749 TI - Prediction of physiological arousability: a validation of the Arousal Predisposition Scale. AB - The Arousal Predisposition Scale (APS) is a brief (12-item) scale, that purportedly measures arousability, and has already been shown to predict task related arousal changes measured via self-report indexes. To determine if APS scores could predict individual differences in physiological measures of arousal, it was administered to 239 subjects. From this group, 9 highly arousable subjects and 9 low arousable subjects (based on APS scores) were selected. Each subject was repeatedly exposed to an arousing stimulus consisting of a 105 dB white noise. Electrodermal activity and the electromyographic response were used as indexes of change in autonomic and affective arousal. Subjects who scored highly arousable on the APS showed a greater change in electrodermal and electromyographic response than subjects judged low on arousability. This appears to validate the usefulness of the APS as a measure of individual differences in predisposition toward arousability. PMID- 8442750 TI - Dimensions of suicidal ideation in psychiatric inpatients. AB - The computer-assisted version of the Beck Scale for Suicide Ideation (BSI; Beck, Steer & Ranieri, Journal of Clinical Psychology, 44, 499-505, 1988) was administered to 330 psychiatric inpatients diagnosed with mixed disorders. The BSI is a 19-item self-report instrument for measuring the intensity, duration and specificity of a patient's thoughts and plans about committing suicide. Of the 330 inpatients, 115 (34.8%) were classified as suicide ideators according to the BSI. Controlling for gender, a maximum-likelihood principal factor analysis of the partial intercorrelation matrix among the ideators' BSI items was conducted using an oblique rotation. Three factors were found that reflected Desire for Death, Preparation for Suicide and Active Suicidal Desire. The importance of assessing specific factors of suicidal ideation was discussed. PMID- 8442751 TI - Protein kinase C: a key factor in the regulation of tumor cell adhesion to the endothelium. PMID- 8442752 TI - Impaired antioxidant status in diabetic rat liver. Effect of vanadate. AB - In vivo effects of vanadate on the antioxidant status of control and alloxan diabetic rats liver were examined. The increased oxidative stress during diabetes caused a decline in the activities of glutathione peroxidase (GPx), catalase (CAT), CuZn superoxide dismutase (CuZn-SOD) and Mn-superoxide dismutase (Mn-SOD) in the liver. Reduced glutathione (GSH) was also depleted, but the level of oxidized glutathione and glutathione reductase activity remained unchanged in the livers of diabetic rats. Vanadate treatment of diabetic rats (0.6 mg/mL in drinking water) resulted in almost complete restoration of GPx and Mn-SOD but caused only a partial restoration of CuZn-SOD. However, CAT and GSH were found to be lowered further in vanadate-treated diabetic rats as compared to untreated diabetic rat. Similar decreases in CAT and GSH levels were also observed in the vanadate-treated controls. These results suggest that vanadate, an insulin mimetic agent, effectively normalized hyperglycemia, but unlike insulin, could not completely restore the altered endogenous defence mechanisms in diabetic liver. PMID- 8442753 TI - Effects of the glucocorticoid agonist, RU28362, and the antagonist RU486 on lung phosphatidylcholine and antioxidant enzyme development in the genetically obese Zucker rat. AB - The biochemical maturation of the lung in late gestation and in the young animal is regulated by glucocorticoids. The present study was aimed at dissociating the different glucocorticoid receptor sites involved in these regulatory functions. The obese Zucker rat was selected as a model for this study as it exhibits hypersensitivity to glucocorticoid hormone action by virtue of its elevated receptor numbers and activity. Two synthetic steroid analogues were administered to obese animals; RU28362, a specific type II receptor agonist, and the type II antagonist RU486. RU28362 promoted a strong catabolic effect, which was associated with reduced food intake and the abolition of growth in the rats. The agonist, RU28362, attenuated developmental increases in antioxidant enzyme activities, and altered the growth of the tissue. At the age studied, development of the lung phosphatidylcholine (PC) system was almost complete, but RU28362 increased disaturated PC 16:0/16:0 concentrations by almost 2-fold, and altered the molecular composition of total pulmonary PC. RU486 attenuated the growth of the rats and reduced their food intake. Treatment with the type II antagonist attenuated lung growth and increased the activities of pulmonary copper zinc (Cu/Zn) and manganese (Mn) superoxide dismutases. RU486 had no effect on lung PC concentrations and molecular composition. The data suggest a role for type I glucocorticoid receptors in the regulation of the antioxidant enzyme system in the lung, as type II antagonism will channel endogenous glucocorticoid binding to the type I site. Type II receptor binding would appear to play a role in regulating the lung PC content. PMID- 8442754 TI - Ethanol metabolism in isolated hepatocytes. Effects of methylene blue, cyanamide and penicillamine on the redox state of the bound coenzyme and on the substrate exchange at alcohol dehydrogenase. AB - Ethanol metabolism in hepatocytes increases the NADH/NAD+ ratio. The mechanism was investigated by measurements of the redox state of the coenzyme bound to alcohol dehydrogenase and of ethanol-acetaldehyde exchange and concomitant hydrogen transfer between ethanol molecules. Isolated hepatocytes from fed rats were incubated with cyclohexanone and cyclohexanol or with [1,1-2H2]-and [2,2,2 2H3]ethanol, followed by gas chromatographic determination of the redox state and isotope analysis of the ethanol by gas chromatography-mass spectrometry, respectively. Cyanamide and methylene blue decreased the redox shift caused by ethanol and increased the rates of acetaldehyde reduction during the exchange. Both drugs increased the extent of hydrogen transfer between ethanol molecules during oxidoreduction. Penicillamine had no significant effect on the ethanol induced change in redox state of the bound coenzyme although it decreased the rate of acetaldehyde reduction. The results indicate that methylene blue inhibits aldehyde dehydrogenase and that accumulation of acetaldehyde decreases the redox effects of ethanol. The redox effect appears to result primarily from rapid elimination of acetaldehyde and equilibration with the NAD system on the alcohol dehydrogenase, but is not enhanced by further decreases in acetaldehyde concentration. Thus, penicillamine could probably be used to decrease the concentration of acetaldehyde without increasing the redox effects. PMID- 8442755 TI - Detection of the degradation products of bradykinin by enzyme immunoassays as markers for the release of kinin in vivo. AB - We developed an enzyme immunoassay (EIA) specific for Arg1-Pro2-Pro3-Gly4-Phe5 ([1-5]-BK) for determination of the levels of this peptide in biological fluids. Previously developed EIAs for bradykinin (BK) and for des-Phe8-Arg9-BK ([1-7]BK) were also used. Incubation of rat plasma with glass powder resulted in the transient appearance of BK. A degradation product, [1-7]BK, could be detected in the incubation mixture for a longer period of time. When compared with BK and [1 7]BK, a larger amount of [1-5]BK was detectable even longer. In carrageenan induced pleurisy in rats, which was associated with a peak rate of plasma exudation 5 hr after administration of carrageenan, BK was undetectable (< 160 pg/rat) in the pleural exudates. By contrast, [1-7]BK was detectable over the entire course of the inflammatory response. A larger amount of [1-5]BK was detectable. The peak level of [1-5]BK was 6050 +/- 1050 pg/rat, 5 hr after administration of carrageenan. Inhibition of the generation of BK by intrapleural administration of soy bean trypsin inhibitor (0.3 mg/rat) 30 min before collection of pleural fluid resulted in significant reductions in the levels of both [1-7]BK (by 51-65%) and [1-5]BK (by 63-79%) in the exudates 3, 7 and 19 hr after administration of carrageenan. Intraperitoneal administration of captopril (10 mg/kg) caused a marked reduction (by 98%) in levels of [1-5]BK in exudates 3 hr after administration of carrageenan. The reduction was accompanied by an increase in the level of BK up to 1250% of that in untreated rats. These results indicate that the newly developed EIA for [1-5]BK might be a useful tool for verifying the release of kinin in vivo. PMID- 8442756 TI - The effect of hypoxia on propranolol clearance during antegrade and retrograde flow in the isolated perfused rat liver preparation. AB - We investigated, using the single-pass isolated perfused rat liver preparation, whether the centrilobular location of hepatic oxidative drug metabolism could be a contributing factor to the marked sensitivity of drug oxidation to hypoxia. Livers (N = 7) were each perfused for 130 min with 2 micrograms/mL (+) propranolol, a drug metabolized almost entirely by oxidation in the rat. The direction of flow was reversed after 60 min, the order of flow direction being randomized. Normal oxygenation was used during the first 30 min of antegrade and of retrograde perfusion, but in the second 30 min perfusate was equilibrated with a N2/O2 mixture designed to reduce hepatic oxygen delivery by half. During normal oxygenation there was no significant difference between antegrade and retrograde perfusion in hepatic oxygen delivery and physiological parameters such as oxygen consumption and extraction, perfusion pressure and bile flow. During hypoxia, mean oxygen delivery was slightly lower with retrograde perfusion (retrograde: mean = 2.37 mumol/min/g liver, range = 1.56-3.17; antegrade: mean = 2.90 mumol/min/g liver, range = 1.96-4.08; P = 0.04), but there was no significant difference in physiological parameters within each liver (P > 0.05). Propranolol clearance during normal oxygenation was similar to the perfusion rate (10 mL/min) and was the same for both directions of perfusion (antegrade 9.88 +/- 0.07 mL/min, retrograde 9.88 +/- 0.13 mL/min, P > 0.05). Hypoxia reduced propranolol clearance substantially, but the decrease was significantly greater with antegrade perfusion (5.65 +/- 1.89 mL/min) than with retrograde perfusion (6.76 +/- 1.95 mL/min, P = 0.014). Oxidative drug metabolism is located primarily in the centrilobular zone and sinusoidal oxygen concentration is lowest in the "downstream" zone with both antegrade and retrograde perfusion. These findings suggest that the centrilobular location of propranolol metabolism may influence the effect of hypoxia on propranolol elimination, but is not a major contributor to the marked sensitivity of propranolol elimination to hypoxia antegrade perfusion. PMID- 8442757 TI - Effects of retinoic acid on lipoprotein lipase activity and mRNA level in vitro and in vivo. AB - This study was designed to determine whether all-trans retinoic acid altered lipoprotein lipase (LPL) activity and mRNA levels in vitro and tissue LPL mRNA levels in vivo. Incubation of adipocytes or adipose tissue for up to 12 hr with 10(-6) or 10(-5) M all-trans retinoic acid did not decrease LPL activity. There was no change in LPL mRNA levels following 3 hr incubation of adipocytes with all trans retinoic acid. Feeding all-trans retinoic acid for 4 days led to a significant decrease in adipose tissue LPL activity but no change in heart enzyme activity. Retinoic acid did not alter the increase in heart LPL activity observed with fasting. There were no changes in LPL mRNA levels in adipose tissue, heart or liver. Retinoic acid does not have an acute direct effect on adipose tissue LPL activity. The observed decrease in adipose tissue LPL activity in vivo is not due to alterations in mRNA levels and may be a secondary effect of retinoic acid. PMID- 8442758 TI - Interleukin 2 induction of cytochrome P450-linked monooxygenase systems of rat liver microsomes. AB - The effects of interleukin 2 (IL-2), a pivotal cytokine for generating an effective immune response, on rat liver microsomal cytochrome P450-linked monooxygenase systems were investigated by measuring the contents of cytochromes b5 and P450, and the activities of various xenobiotic-metabolizing enzymes [debrisoquine and bufuralol monooxygenases (CYP2D), 7-ethoxycoumarin O deethylase, benzphetamine N-demethylase, aniline hydroxylase and p-nitroanisole N demethylase]. The enzymatic activities except for p-nitroanisole N-demethylase and aniline hydroxylase were increased approximately to 1.3-fold of those of untreated liver microsomes following intraperitoneal injection of IL-2 (15 U/rat). However, the amount of immunoreactive b5 protein, and the activities of aniline hydroxylase and p-nitroanisole N-demethylase were not changed by injection of IL-2. To elucidate further the mechanism of the induction of CYP2D by IL-2, quantitative analyses of immunoreactive CYP2D protein and its mRNA were conducted by western blot and slot blot hybridization analyses. The results indicated that IL-2 induced an increase in the amounts of immunoreactive CYP2D protein and its mRNA. These enzymatic activities were thus up-regulated at the mRNA level. PMID- 8442759 TI - Bradykinin stimulates phospholipase D in primary cultures of guinea-pig tracheal smooth muscle. AB - Conditions were established for the primary culture of guinea-pig tracheal smooth muscle cells, the identity of which was confirmed by the presence of smooth muscle alpha-actin by western blotting. Cells were preincubated with [3H]palmitate which was incorporated, almost exclusively, into phosphatidylcholine. When these cells were stimulated by either bradykinin or phorbol 12-myristate 13-acetate (PMA), in the presence of butan-1-ol, the non metabolizable product [3H]phosphatidylbutanol ([3H]PtdBut) accumulated by virtue of the phosphatidyltransferase activity of phospholipase D. The activation of phospholipase D by bradykinin was inhibited by 86 +/- 11% (N = 3 experiments) in the presence of the protein kinase C inhibitor, staurosporine (1 microM) and by 88 +/- 11% (N = 3 experiments) in cells that had been chronically treated with PMA to down-regulate their protein kinase C. PMA-stimulated phospholipase D was similarly affected (92 +/- 2% inhibited by staurosporine, 87 +/- 6% inhibited by protein kinase C down-regulation). Removal of extracellular Ca2+ markedly reduced the bradykinin-stimulated phospholipase D response (by 73 +/- 10%, N = 3 experiments) but had only a limited effect upon PMA-stimulated phospholipase D activity (by 23 +/- 6%, N = 3 experiments). [AIF4](-)-stimulation of the cells also resulted in the activation of phospholipase D, indicating the involvement of a G-protein. However, this was not Gi since pertussis-toxin pretreatment of the cells failed to abolish either bradykinin-stimulated inositol (1,4,5)trisphosphate formation or [3H]PtdBut accumulation. Western blotting revealed the presence of Gq/G11 which couples to the inositol lipid-directed phospholipase C. Indomethacin (10 microM) was without effect upon bradykinin stimulated phospholipase D activity, suggesting that the bradykinin effects were not mediated indirectly by cyclooxygenase products. The role of phospholipase D activation in tracheal smooth muscle may be to, indirectly, produce diacylglycerol for the activation of protein kinase C which has been implicated in sustained contraction. However, the immediate product of phospholipase D, phosphatidate, has been proposed to have a number of second messenger roles and may itself, by an undefined mechanism, be involved in the sustained contraction of airway smooth muscle. PMID- 8442760 TI - Evidence for the involvement of a carboxyl group in the vicinity of the MK801 and magnesium ion binding site of the N-methyl-D-aspartate receptor. AB - A series of protein modifying reagents were tested for their effects on the specific binding of [3H]MK801 to adult rat brain membranes. N-Bromosuccinimide, acetyl imidazole, 2,3-butanedione, 5,5'-dithiobis-(2-nitrobenzoic acid) and dithiothreitol all had no significant effect on binding. The carboxylic acid residue modification reagent, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDAC), inhibited [3H]MK801 specific binding in a dose-dependent manner with an IC50 = 1.9 mM. The inhibition by EDAC was due to a decrease in the Bmax with no change in KD. The inhibition of [3H]MK801 binding by EDAC was not prevented by prior incubation with competitive antagonists. Protection against EDAC inactivation was obtained, however, in a dose-dependent manner by preincubation with the divalent cations, Ca2+ and Mg2+, but not Zn2+. These results suggest that EDAC modifies an important carboxyl group located within the voltage dependent Mg2+ binding site of the N-methyl-D-aspartate receptor. This modification yields a decrease in the specific [3H]MK801 binding activity thus demonstrating a close association between the two allosteric regulatory sites. PMID- 8442761 TI - The effects of beta-phorbol-12,13 dibutyrate on agonist-induced increases in [Ca2+]i in N1E-115 cells. Differential modulation of responses to angiotensin II and bradykinin. AB - Addition of angiotensin II (A2; 500 nM) to populations of fura-2-loaded N1E-115 cells resulted in a transient increase in intracellular calcium which was abolished by pre-treatment with the phorbol ester, beta-phorbol-12,13 dibutyrate (PDBu) (1.5 microM). The inhibitory effects were reversed by the protein kinase C inhibitor, staurosporine (150 nM), and down-regulation of protein kinase C was observed over 48 hr. Responses to maximally effective concentrations of histamine (300 microM), ATP (100 microM), UTP (100 microM) and carbachol (100 microM) were similarly inhibited by phorbol pre-treatment but the response to bradykinin (BK) (100 nM) was unaffected. When the concentrations of BK and A2 were adjusted to produce the same-sized calcium signals, PDBu pre-treatment abolished the response to A2 but only partially inhibited the response to BK. From the data presented here we can conclude that the calcium response to BK in N1E-115 cells is less susceptible to the inhibitory effects of protein kinase C activation than the response produced by A2. PMID- 8442762 TI - The effects of a benzoic acid mustard derivative of distamycin A (FCE 24517) and related minor groove-binding distamycin analogues on the activity of major groove binding alkylating agents. AB - The distamycin derivative FCE 24517 is a potent antitumour agent. Efforts have been made towards elucidating the mechanism of action of this compound which, to date, have highlighted a high level of DNA sequence specificity for covalent adduct formation. Compared to classical alkylating agents, FCE 24517 forms very few covalent adducts with double-stranded DNA, and thus appears to be a weak alkylating agent. Examination of the effects of this minor groove-binding agent on the major groove of DNA have been facilitated by use of the alkylating agents mustine, melphalan, dabis maleate, quinacrine mustard and uracil mustard. Pretreatment of plasmid DNA with FCE 24517 followed by reaction with any one of these mustards gave rise to a marked abolition of N-7 guanine adduct formation, as assayed by Maxam and Gilbert sequencing gels. The smallest effect was seen for quinacrine mustard, whereas total abolition of N-7 guanine alkylation was seen with uracil mustard. Using related structural analogues of FCE 24517 in the same experiments, it was not possible to reproduce this effect, with very few exceptions. Some effects were seen when using distamycin A itself in these experiments, although these were marginal compared to those seen for FCE 24517. We were able to extrapolate our findings to a whole cell system using murine L 1210 leukaemia cells. Alkaline elution experiments showed that treatment of cultured cells with FCE 24517 followed by either mustine or uracil mustard caused a marked inhibition of DNA interstrand crosslink formation, compared to treatment with mustine or uracil mustard alone. The present study has demonstrated the marked effect that FCE 24517 has upon the reactivity of double-stranded DNA, an effect possibly separate from that of its alkylating function. This study has highlighted the complex nature of the DNA interactive compound FCE 24517 which possess potent and broad spectrum antitumour activity. PMID- 8442763 TI - Increased glucuronidation of thyroid hormone in hexachlorobenzene-treated rats. AB - Metabolism of thyroid hormones was investigated in WAG/MBL rats that had been exposed to hexachlorobenzene (HCB). Serum thyroxine (T4) levels were lowered by 35.5%, whereas triiodothyronine (T3) levels were not changed. Bile flow, as well as T4 excretion in bile were increased by HCB treatment. Analysis of bile by HPLC revealed a more than 3-fold increase of T4 glucuronide (T4G) and a concomitant reduction of non-conjugated T4. T4 UDP-glucuronyltransferase activity (T4 UDPGT) activity in hepatic microsomes was increased more than 4.5-fold in animals exposed to HCB. p-Nitrophenol (PNP) UDPGT showed a comparable increase by HCB. Both T3 and androsterone UDPGT activities were low in WAG/MBL rats compared with normal Wistar rats. T3 UDPGT activity was increased 2.5-fold by HCB, but androsterone UDPGT activity was unchanged. These results suggest that T4 is a substrate for HCB-inducible PNP UDPGT and T3 for androsterone UDPGT. In the absence of the latter, T3 is also glucuronidated to some extent by PNP UDPGT. Type 1 iodothyronine deiodinase activity was decreased by HCB treatment. It is concluded that decreased T4 levels in serum of animals after exposure to HCB may be due to a combined effect of displacement of T4 from carriers, an increased glucuronidation of T4 and enhanced bile flow. PMID- 8442764 TI - Isoenzyme selective irreversible inhibition of rat and human glutathione S transferases by ethacrynic acid and two brominated derivatives. AB - In the present study it has been shown that ethacrynic acid can inhibit glutathione S-transferase (GST) of the pi-class irreversibly. [14C]Ethacrynic acid, 0.8 nmol/nmol human P1-1 and 0.8 nmol/nmol rat GST 7-7 could be incorporated, resulting in 65-93% inhibition of the activity towards 1-chloro-2,4 dinitrobenzene (CDNB). Isoenzymes of the alpha- and mu-class also bound [14C]ethacrynic acid, however without loss of catalytic activity. Incorporation ranged from 0.3 to 0.6 and 0.2 nmol/nmol enzyme for the mu- and alpha-class GST isoenzymes, respectively. For all isoenzymes, incorporation of [14C]ethacrynic acid could be prevented by preincubation with tetrachloro-1,4-benzoquinone, suggesting, that a cysteine residue is the target site. Protection of GST P1-1 against inhibition by ethacrynic acid by the substrate analog S-hexylglutathione, indicates an active site-directed modification. The monobromo and dibromo dihydro derivatives of ethacrynic acid were synthesized in an effort to produce more reactive compounds. The monobromo derivative did not exhibit enhanced irreversible inhibitory capacity. However, the dibromo dihydro derivative inhibited both human and rat GST isoenzymes of the pi-class very efficiently, resulting in 90-96% inhibition of the activity towards CDNB. Interestingly, this compound is also a powerful irreversible inhibitor of the mu-class GST isoenzymes, resulting in 52-70% inhibition. The two bromine atoms only marginally affect the strong (reversible) competitive inhibitory capacity of ethacrynic acid, with IC50 (microM) of 0.4-0.6 and 4.6-10 for the mu- and pi-class GST isoenzymes, respectively. PMID- 8442765 TI - Subcellular localization of cytochrome P450, and activities of several enzymes responsible for drug metabolism in the human brain. AB - We studied the subcellular distribution of cytochrome P450 and related monooxygenase activities in six regions of human brains removed at autopsy. The content of total cytochrome P450 was found to be at least nine times higher in the mitochondrial fraction than in the microsomes in all the regions studied. However, cytochrome P450-dependent enzymatic activities which are representative of different isoforms metabolizing exogenous molecules exhibited a microsomal prevalence, a situation previously observed in rat brain. The other drug metabolizing enzymes catalysing functionalization and conjugation reactions, presented the following characteristics in human brain: (i) a low activity of NADPH-cytochrome P450 reductase, which also catalyses the reduction of some xenobiotics; (ii) a high specific activity of the membrane-bound epoxide hydrolase; (iii) among the enzymes catalysing conjugation reactions, 1-naphthol UDP-glucuronosyltransferase activity was barely or not detectable, whereas the mean glutathione-S-transferase activity was 15 times higher than the activity measured in rat brain. The presence of several drug-metabolizing enzyme activities in human brain microvessels, and particularly the high activity of epoxide hydrolase, suggests a participation of these enzymes in the metabolic blood-brain barrier. PMID- 8442766 TI - Circadian rhythm of orotate phosphoribosyltransferase, pyrimidine nucleoside phosphorylases and dihydrouracil dehydrogenase in mouse liver. Possible relevance to chemotherapy with 5-fluoropyrimidines. AB - In female mice (30-35 g) maintained in standardized conditions of 12 hr light (0600-1800 hr) alternating with 12 hr darkness (1800-0600 hr), food and water ad lib., there was a 24-hr cycle change (P < 0.0001, Cosinor analysis) in the activity of hepatic orotate phosphoribosyltransferase (OPRTase; EC 2.4.2.10), uridine phosphorylase (UrdPase; EC 2.4.2.3), and dihydrouracil dehydrogenase (DHUDase; 1.3.1.2) but not thymidine phosphorylase (EC 2.4.2.4). The peaks of both OPRTase and UrdPase activities occurred in the activity span at around 18 and 15 hours after light onset (HALO) and the trough at 6 and 3 HALO, respectively, when samples were taken every 4 hr. Conversely, the peak of DHUDase occurred in the rest span at around 3 HALO and the trough at 15 HALO. The maximal enzyme activities (3146 +/- 172, 561 +/- 25, and 6.7 +/- 0.7 pmol/min/mg protein) was 210, 400 and 560% higher than the minimal activities (1507 +/- 172, 139 +/- 25, and 1.2 +/- 0.7 pmol/min/mg protein), for OPRTase UrdPase, and DHUDase, respectively. A circadian rhythm was also observed when the light-dark cycle was shifted (reverse cycle) so that the lights went on at 2200 hr and off at 1000 hr. Under the reverse cycle condition there was a corresponding shift in UrdPase and DHUDase activities with a period of 1 hr difference in the time of maximum and minimum enzyme activities. OPRTase, on the other hand, showed little change after 4 weeks of adaptation under the reverse light cycle. The circadian rhythm of these key enzymes of pyrimidine metabolism, the interrelationship of their activities, and their role in the regulation of uridine bioavailability could be of particular significance in modulating the therapeutic regimens with 5 fluorinated pyrimidines. PMID- 8442767 TI - Induction of the c-jun proto-oncogene by a protein kinase C-dependent mechanism during exposure of human epidermal keratinocytes to ethanol. AB - The present work demonstrates that ethanol induces expression of the c-jun proto oncogene in human keratinocytes. Increased c-jun mRNA levels were detectable at 1 hr of exposure to 1% ethanol and at 24 hr remained above that in control keratinocytes. An increase in c-jun expression was also detectable at ethanol concentrations of 0.1 and 0.5%. Similar findings were obtained for the related jun-B and c-fos early response genes. The results also demonstrate that ethanol exposure is associated with increases in protein kinase C activity in both the cytosol and membrane fractions. This increase was detectable at 5 min and maximal at 30-60 min. The finding that induction of c-jun expression by ethanol was inhibited by the isoquinolinesulfonamide derivative H7, but not by HA1004, suggested that this effect is mediated by protein kinase C. Furthermore, down regulation of protein kinase C by prolonged exposure to 12-O-tetradecanoylphorbol 13-acetate was associated with a block in ethanol-induced c-jun expression. We also demonstrated that ethanol exposure is associated with rapid (5-30 min) increases in intracellular levels of diradylglycerol. Taken together, these findings demonstrate that the exposure of keratinocytes to ethanol results in the activation of protein kinase C and c-jun expression. PMID- 8442769 TI - Sebacic acid binding to human plasma albumin. AB - Sebacic (decanedioic) acid is a dicarboxylic acid proposed recently as an alternative energy substrate in total parenteral nutrition. In this paper, binding of sebacic acid to defatted human plasma albumin, also in the presence of decanoic acid, was studied by means of equilibrium dialysis. In addition, the binding of sebacic acid in human serum was investigated. Binding to defatted albumin was analysed by a model with two independent classes of sites with different affinity constants. The fitting procedure took into account some of the measurement errors that are likely to affect the equilibrium dialysis technique. We found for sebacic acid one binding site with affinity constant 3.69 x 10(4) M 1 and four to five sites with affinity constant 7.14 x 10(2) M-1. Association constants for decanoic acid are 3-4-fold larger than those of sebacic acid. Data of binding of sebacic acid in human serum suggested that only three to five of the low affinity sites are available for binding. When disodium sebacate is administered i.v. for total parenteral nutrition, a substantial fraction of sebacic anions is likely to be bound in serum. PMID- 8442768 TI - Cytotoxic effect of thiacarbocyanine dyes on human colon carcinoma cells and inhibition of bovine heart mitochondrial NADH-ubiquinone reductase activity via a rotenone-type mechanism by two of the dyes. AB - Five lipophilic-cationic thiacarbocyanine compounds differing in the side chains (methyl-S13, ethyl-S23, propyl-S33, butyl-S43, and pentyl-S53) and a related thiadicarbocyanine compound with ethyl side chains (S25) exhibited a selective cytotoxic effect on human colon carcinoma cells compared to green monkey kidney epithelial cells. The inhibitory concentration for 50% inhibition of growth (IC50) for the carcinoma cells ranged from 13 nM for S13 and S23 to 160 nM for S25. The carcinoma cells were 4- to 100-fold more sensitive than the normal cells. Two of the five compounds, S13 and S23, selectively inhibited NADH oxidase activity with bovine heart submitochondrial particles (SMP). There was no discernable inhibitory effect by the other three thiacarbocyanine compounds on electron transport chain activity. The primary site of inhibition within the respiratory chain for S13 and S23 appeared to be the NADH to coenzyme Q portion of the mitochondrial electron transport chain. Artificial electron acceptors for this segment of respiratory chain were used to localize the inhibitory site. Using SMP, both S13 and S23 inhibited reduction of menadione, duroquinone, and coenzyme Q. Using purified complex I (NADH-ubiquinone reductase) (EC 1.6.99.3), S13 slightly inhibited reduction of juglone, duroquinone, and coenzyme Q, whereas S23 had no effect on any of the substrates. When rotenone-saturated SMP were used, the inhibitory effects of S13, but not S23, on the reduction of menadione were abolished, as was the inhibitory effect of S13 on coenzyme Q reduction when rotenone-insensitive complex I was used as the source of the enzyme. These results suggest that (1) S13 and S23 inhibition of NADH-ubiquinone reductase activity is enhanced by the membrane environment of the enzyme, and (2) the inhibition appears to be in part akin to the inhibiting mode of rotenone. PMID- 8442770 TI - Regulation of eicosanoid biosynthesis in the macrophage. Involvement of protein tyrosine phosphorylation and modulation by selective protein tyrosine kinase inhibitors. AB - The protein tyrosine kinase (PTK) inhibitor genistein has been demonstrated to inhibit platelet-activating factor-stimulated prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS)-primed P388D1 macrophage-like cells (Glaser et al., J Biol Chem 265: 8658-8664, 1990). Therefore, the role of PTK in eicosanoid biosynthesis was investigated in murine resident peritoneal macrophages using genistein and tyrphostin-25, selective PTK inhibitors. Genistein, a competitive inhibitor of ATP binding on PTK, inhibited PGE2 production (IC50 = 20 microM) in response to zymosan, calcium ionophore A23187, and phorbol myristate acetate stimulation. Genistein also inhibited leukotriene C4 (LTC4) production in response to zymosan and calcium ionophore A23187 (IC50 = 10 and 15 microM, respectively) stimulation. Tyrphostin-25, a competitive inhibitor of substrate binding on PTK, inhibited zymosan-stimulated PGE2 and LTC4 production, IC50 = 20 and 7 microM, respectively. Neither genistein nor tyrophostin-25 had any effect on human synovial fluid phospholipase A2 (PLA2) activity in vitro or on cyclooxygenase activity in the intact macrophage; however, tyrphostin-25 did affect 5-lipoxygenase activity (determined from the metabolism of exogenously applied arachidonic acid). These results suggest PTK-mediated phosphorylation as a common event in the signal transduction mechanisms of different stimuli which activate PLA2 for arachidonic acid release and subsequent eicosanoid biosynthesis. Immunoblot analyses of zymosan-stimulated peritoneal exudate cells with the phosphotyrosine monoclonal antibody clone 4G10 demonstrated an increase in protein phosphotyrosine levels in eight major protein bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis: p59, 71, 76, 90, 100, 112, 125 and 150. Maximal phosphorylation of these protein substrates occurred after 1-2 min stimulation. Zymosan and LPS stimulation of peritoneal exudate cells produced similar patterns of protein tyrosine phosphorylation. Zymosan-stimulated tyrosine phosphorylation was inhibited by tyrphostin-25 in a concentration-dependent manner between 10 and 60 microM, demonstrating a similar concentration response between effects on tyrosine phosphorylation and eicosanoid biosynthesis in the murine peritoneal macrophage. The use of selective PTK inhibitors suggests a common role for PTK and tyrosine phosphorylation in eicosanoid biosynthesis in the murine peritoneal macrophage. PMID- 8442771 TI - Protein binding and hepatobiliary distribution of valproic acid and valproate glucuronide in rats. AB - The protein binding and hepatobiliary distribution of valproic acid (VPA) and its glucuronide conjugate (V-G) were examined in rats with a combination of in vitro and ex vivo protocols. VPA was moderately bound to proteins in both serum and hepatic cytosol, and the degree of binding was lower ex vivo than in vitro. V-G, which was more highly bound than VPA ex vivo in serum, may have displaced the parent drug from its binding sites when VPA was administered in vivo. Examination of ex vivo hepatic subcellular distribution revealed that VPA localization tended to be high in cytosol and low in the microsomal fraction; V-G appeared to be distributed evenly throughout the cell although V-G concentrations within the liver were very low. The steady-state elimination rate of VPA did not increase proportionately with increasing steady-state concentrations of unbound VPA in serum, consistent with saturable systemic elimination of the drug. In contrast, steady-state VPA elimination was related linearly to unbound cytosolic VPA concentrations. Moreover, a nonlinear relationship between the unbound concentrations of VPA in hepatic cytosol and serum was observed, consistent with saturable distribution of the unbound drug between the two compartments in vivo. These observations suggest that the nonlinear elimination of VPA in rats may be due to concentration-dependent penetration of the drug into the liver as opposed to saturable biotransformation. PMID- 8442772 TI - Inhibition of low density lipoprotein oxidation by thyronines and probucol. AB - Oxidation of low density lipoproteins (LDL) results in increased macrophage uptake of LDL which may contribute to the formation of macrophage-derived foam cells in the early atherosclerotic lesion. In this study we show that thyroxine (T4), its optical antipodes, certain desiodo analogs and probucol inhibited cupric sulfate-catalyzed oxidation of human LDL in a concentration-dependent manner as assessed by measuring the electrophoretic mobility, thiobarbituric acid reactive substances (TBARS) and LDL degradation in mouse macrophages. In Cu(2+) catalyzed LDL oxidation at 24 hr, the TBARS level was 80 nmol/mg LDL protein/24 hr incubation. The concentrations (microM) of each agent producing 50% inhibition in the formation of oxidized LDL (IC50) for TBARS, electrophoretic mobility and macrophage degradation, respectively, were 1.13, 1.27 and 1.30 for reversed triiodothyronine; 1.33, 1.80 and 1.27 for triiodothyronine; 1.33, 1.37 and 1.37 for racemic thyroxine, DL-T4; 1.10, 1.40 and 1.50 for L-T4; 1.13, 1.33 and 1.23 for D-T4; and 1.47, 1.63 and 1.37 for probucol. No differences in inhibitory potency were observed when rT3, T3, the optical antipodes of T4 and the hydrophobic antioxidant drug probucol were compared. In air-induced LDL oxidation, TBARS was 16.1 nmol/mg LDL protein/6-hr incubation. The IC50 concentrations (microM) for TBARS and diene conjugation, respectively, were 0.187 and 0.336 for D-T4; 0.205 and 0.243 for L-T4 and 1.30 and 3.02 for probucol. With air-induced LDL oxidation conditions, the L-T4 concentrations included the physiological range, and thyroid-binding globulin did not modify the inhibitory effect of the endogenous enantiomer, L-T4. Putative uptake of this stereoisomer into LDL inhibited oxidation of these lipoproteins. Since concentrations of these thyronines which blocked air-induced LDL oxidation were in the physiological range, we conclude that thyronines, like the pharmacological agent probucol, limit the oxidative modification of LDL and thus may serve as natural inhibitors of atherogenesis. PMID- 8442773 TI - The effect of hypoxia and acidosis on propranolol clearance in the isolated perfused rat liver preparation. AB - The effect of hypoxia and acidosis on the elimination of an oxidatively metabolized drug, S-propranolol, was examined in the single-pass isolated perfused rat liver (IPRL). The experiments (N = 6) consisted of four consecutive 30 min phases: normal pH (pH 7.4)/normal oxygen delivery, normal pH/hypoxia, hypercapnic acidosis (pH 7.1)/normal oxygenation and hypercapnic acidosis/hypoxia. Hypoxia and acidosis were produced by equilibrating the perfusate with appropriate mixtures of O2, N2 and CO2. With normal oxygen delivery there was no difference in hepatic clearance of propranolol between normal pH and acidosis (9.65 +/- 0.34 and 9.78 +/- 0.11 mL/min, respectively. P < 0.05). During hypoxia, propranolol clearance was impaired to a similar extent under both pH conditions (7.41 +/- 0.97 and 8.06 +/- 0.81 mL/min, respectively, P > 0.05). Therefore, respiratory acidosis does not affect the clearance of propranolol by the IPRL, nor does it influence the sensitivity of propranolol clearance to hypoxia. Neither acidosis nor hypoxia resulted in a significant reduction in bile flow compared with the normal pH/normal oxygen phase and there was no correlation between bile flow and perfusate bicarbonate concentration (P > 0.05). PMID- 8442774 TI - Lactational transfer of 2,4,5,2',4',5'-hexachlorobiphenyl but not 3,4,3',4' tetrachlorobiphenyl, induces neonatal CYP4A1. AB - In order to study the lactational transfer of polychlorinated biphenyls, lactating rats were treated with a low dose of either 3,4,3',4' tetrachlorobiphenyl (TCB), 2,4,5,2',4',5'-hexachlorobiphenyl (HCB) or a combination of TCB and HCB. For comparison, animals were also treated with Aroclor 1254, Lactational transfer of these chemicals resulted in the induction of neonatal hepatic CYP4A haemoproteins, the isozymes induced being dependent on the compound used. CYP4A1 was not detected in control, TCB or HCB/TCB-treated animals, but was induced in neonates when mothers were treated with HCB or Aroclor 1254. In the case of Aroclor 1254, the magnitude of the effect appeared to be dependent on the dose used. CYP4A2 and CYP4A3 were induced in the neonates when mothers were treated with Aroclor 1254 but not with the other agents used. It appears that TCB induces novel members of the CYP4A gene family. The present study provides immunochemical evidence for the ability of congeneric polychlorinated biphenyls to modulate differentially the expression of CYP4A isozymes in lactating mothers and their suckling offspring. These findings further support the potential hazards induced by lactational transfer of inert lipophilic chemicals and exemplify the complexity of the regulation of genes within this gene family. PMID- 8442775 TI - Inhibition of the G1/S transition in A65 cells by H-7, a protein kinase C inhibitor. AB - The effects of protein kinase inhibitors on the proliferation of A65 murine leukemia cells were studied. The proliferation of phorbol ester-dependent A65 cells was inhibited by N-(2-methylpiperazyl)-5-isoquinolinesulfonamide (H-7), a protein kinase C inhibitor, at a significantly lower concentration than the phorbol ester-independent variant, while both cell types had the same sensitivity to N-[2-[N-[3-(4-chlorophenyl)-1-methyl-2-propenyl]amino]ethyl]-5- isoquinolinesulfonamide, a selective inhibitor of protein kinase A, and staurosporine, a non-selective inhibitor of protein kinases. When the effect of H 7 on the cell cycle was analysed by flow-cytometry, the agent at concentrations that completely inhibited the cell proliferation significantly increased the proportion in the G0/G1 phase of both cell types but decreased that in the S phase, without much change in the G2/M phase. These results suggest that H-7 blocks the G1/S transition by inhibiting protein kinase C, whether the proliferation is dependent on phorbol ester or not. PMID- 8442776 TI - Lack of in vivo evidence of a cytochrome P450 metabolite participating in aminoglycoside nephrotoxicity. AB - Recent in vitro evidence has suggested that the cytotoxicity of aminoglycosides may be mediated by a metabolite generated by the hepatic cytochrome P450 drug metabolizing system. This postulate has been tested by pretreating rats with cobalt protoporphyrin IX (CoP) to suppress hepatic P450 levels prior to administration of gentamicin. CoP pretreatment was observed to suppress antipyrine clearance markedly but not to alter gentamicin nephrotoxicity. PMID- 8442777 TI - Inhibition of phospholipase A2 purified from human herniated disc. AB - The effect on human herniated intervertebral disc phospholipase A2 (HD-PLA2) of a number of retinoids, antirheumatic drugs and reported PLA2 inhibitors was evaluated using autoclaved [1-14C]-oleate-labeled Escherichia coli membranes as the substrate. Dexamethasone, non-steroidal antiinflammatory drugs, aristolochic acid and retinol were inactive, whereas a marked inhibition was found for manoalide, retinal, nordihydroguaiaretic acid and p-bromophenacyl bromide after preincubation with the enzyme (IC50 values 0.25, 4, 5 and 5 microM, respectively). The results are parallel to those obtained with the PLA2 purified from human synovial fluid. PMID- 8442778 TI - Effects of ELF magnetic fields on biological magnetite. PMID- 8442779 TI - Rat liver foci study on coexposure with 50 Hz magnetic fields and known carcinogens. AB - A study was performed to investigate possible interactions by magnetic fields (MF) with the processes of initiation and promotion of chemically induced preneoplastic lesions in rat liver. Male Sprague-Dawley rats were subjected to a 70% partial hepatectomy followed after 24 h by i.p. injection of diethylnitrosamine (DENA) as a tumour initiator. Starting one week after the DENA treatment phenobarbital (PB) was given to promote growth of enzymatically altered foci of liver cells. MF was applied immediately after the partial hepatectomy and continued until sacrifice after 12 weeks of PB exposure. Homogenous horizontal AC magnetic fields with a frequency of 50 Hz and flux densities of 0.5 mu T or 0.5 mT were used. The rats coexposed with MF and DENA plus PB did not gain weight as much as the rats exposed to the chemical agents only. The MF-exposure also resulted in a slight reduction in size and numbers of the focal lesions. The results suggest an interaction of MF with the processes of chemical carcinogenesis either as a result of stress or depending on effects on the proliferation of preneoplastic cells. PMID- 8442780 TI - Determination of the induced ELF electric field distribution in a two layer in vitro system simulating biological cells in nutrient solution. AB - In-vitro studies of biological effects of electromagnetic fields are often conducted with cultured cells either in suspension or grown in a monolayer. In the former case, the exposed medium can be assumed to be homogeneous; however, eventually the cells settle to the bottom of the container forming a two layer system with different dielectric and conductive properties. In the present work the effect of this separation on the electric field distribution is calculated and experimentally measured at selected positions for a commonly used exposure configuration. The settled cell suspension is modeled by a well-defined two layer system placed in a rectangular container with the base of the container parallel to the direction of the magnetic field. Theoretical calculations based on numerical techniques are done for various two layer systems with different conductivities in each layer. The agreement between the theoretical calculations and the experimental measurements is within +/- 1.5 mV/m, or 10% of the maximum induced field when the conductivity of the lower layer is ten times that of the upper layer. This result is well within experimental error. When the thickness of one of the layers is small compared to the thickness of the other layer, it is found that the electric field distribution is essentially that of the homogeneous case. The latter situation corresponds to a typical cell exposure condition. PMID- 8442781 TI - Inter-beat intervals of cardiac-cell aggregates during exposure to 2.45 GHz CW, pulsed, and square-wave-modulated microwaves. AB - Inter-beat intervals of aggregated cardiac cells from chicken embryos were studied during 190 s exposures to 2.45 GHz microwaves in an open-ended coaxial device. Averaged specific-absorption rates (SARs) and modulation conditions were 1.2-86.9 W/kg continuous-wave (CW), 1.2-12.2 W/kg pulse modulation (PW, duty cycle approximately 11%), and 12.0-43.5 W/kg square-wave modulation (duty cycle = 50%). The inter-beat interval decreased during microwave exposures at 42.0 W/kg and higher when CW or square-wave modulation was used, which is consistent with established effects of elevated temperatures. However, increases in the inter beat interval during CW exposures at 1.2-12.2 W/kg, and decreases in the inter beat interval after PW exposures at 8.4-12.2 W/kg, are not consistent with simple thermal effects. Analysis of variance indicated that SAR, modulation, and the modulation-SAR interaction were all significant factors in altering the inter beat interval. The latter two factors indicated that the cardiac cells were affected by athermal as well as thermal effects of microwave exposure. PMID- 8442783 TI - 2D plasmon excitation and nonthermal effects of microwaves on biological membranes. AB - There are several experimental reports that have demonstrated a remarkable increase in conduction of ions along the interface between water and a polar lipid monolayer as contrasted with that in a bulk-water phase. A simple model was developed for the collective ionic modes of a charged spherical membrane that takes the increase into account. Starting from the hydrodynamic equations for surface ions inside and outside a cell, the dispersion relation for intrinsic cellular electrical oscillations was obtained. Properties were calculated for surface-plasmon modes as well as for a resonant response of a charged membrane bilayer to microwave pumping. PMID- 8442782 TI - Effects of a 60 Hz magnetic field on central cholinergic systems of the rat. AB - We studied the effects of an acute (45 min) exposure to a 60 Hz magnetic field on sodium-dependent, high-affinity choline uptake in the brain of the rat. Decreases in uptake were observed in the frontal cortex and hippocampus after the animals were exposed to a magnetic field at flux densities > or = 0.75 mT. These effects of the magnetic field were blocked by pretreating the animals with the narcotic antagonist naltrexone, but not by the peripheral opioid antagonist, naloxone methiodide. These data indicate that the magnetic-field-induced decreases in high affinity choline uptake in the rat brain were mediated by endogenous opioids in the central nervous systems. PMID- 8442784 TI - The effect of moving air on detection of a 60-Hz electric field. AB - Two potential mechanisms in detection of a 60-Hz electric field by albino rats were examined: field-induced movement of the vibrissae and field-induced vibration of the skin. Specifically, the experiment tested field detection in a moving stream of air designed to mask field-induced movement of the skin, fur, and vibrissae. Rats were trained to detect electric fields and were then tested at field intensities from 0-25 kV/m rms. As previously reported, rats demonstrate unmistakable behavioral evidence of field detection at all intensities above 7.5 kV/m. After establishing detection in still air, field detection was re-examined in moving air (average air velocity approximately 2.8-6.8 m/s). The primary result is that the wind produced no change in detection at field intensities above threshold (> 7.5 kV/m). Indeed, at these intensities detection was virtually identical in still and moving air. A secondary finding is that moving air produced statistically significant (P < .05) but apparently contradictory effects on detection when the field intensity was below threshold. On no-field trials the wind lowered scores (i.e., fewer presses on the field-off lever); however, on subthreshold field trials, the wind actually increased detection scores (i.e., more presses on the field-on lever). While this no-field and subthreshold field result is interesting and deserves further study, we place primary emphasis on the finding that, if the field was detectable in still air, it was also detectable in moving air. This result leads us to believe that movement of the vibrissae, fur, or skin is not likely to be the main mechanism of electric-field detection in our subjects. PMID- 8442785 TI - Effects of microwaves on membranes of hematopoietic cells in their structural and functional organization. AB - The role of cell membranes in stimulating and inhibiting the effects of microwaves was investigated in experiments carried out with a suspension of murine bone marrow cells irradiated with microwaves in vitro [f = 2.45 GHz, CW, specific absorption rate (SAR) = 12 W/kg]. Results obtained by means of a structural probe, 2.4-TNS, indicate that no structural changes occur in the region of the protein-lipid interphase under conditions of short-term irradiation with microwaves that induced temperatures in the range 36-45 degrees C (exposure time 315 and 525 s, respectively). Investigation of one functional parameter--the ability to produce hematopoietic colonies in the spleen after transplantation of the bone marrow irradiated in vitro by microwaves--indicated the possibility of affecting stimulatory and inhibitory effects of microwaves by using a blocker of cell receptors, Trimepranol. The role of microwaves as a physical factor interfering in the process of cell proliferation at the level of receptor regulation is discussed. PMID- 8442786 TI - Antonio Pacchioni (1665-1726): early studies of the dura mater. AB - The clustering of arachnoid villi along the sagittal sinus forms what is known as "Pacchioni granulations." These structures were first described in 1705 by Antonio Pacchioni, an Italian scientist. Pacchioni was born in Reggio Emilia, Italy, in 1665, and there he received his degree in medicine. Later he moved to Rome where he built a successful career dedicated to medical practice, research, and teaching. He became a friend of some of the leading scientists of his age: Lancisi, Malpighi, and Morgagni, among others. He devoted himself to elucidating the structure and function of dura mater, and in his studies often used the new technique of maceration of anatomical specimens in various fluids. Among Pacchioni's written works, the Dissertatio Epistolaris de Glandulis Conglobatis Durae Meningis Humanae (1705) deserves the greatest consideration as it contains the first description of arachnoid granulations. He compared dura to cardiac muscle and attributed to its "glandulae" (glands) the faculty of secreting lymph for lubrication of the sliding movements between meninges and brain during contractions. Three centuries after Pacchioni's death in Rome in 1726, the fine structure of arachnoid villi has not been fully elucidated; moreover, many questions related to mechanisms underlying cerebrospinal fluid absorption remain unanswered. PMID- 8442787 TI - Oral rehydration therapy: what are we waiting for? PMID- 8442788 TI - Perinatal infections with Streptococcus pneumoniae. AB - Perinatal infections with Streptococcus pneumoniae although rare, have caused morbidity and mortality in both neonatal and puerperal patients. To determine the incidence of proven pneumococcal sepsis in these patient groups, blood culture records from 1977 to 1989 were reviewed. Of 89 parturient patients with true positive blood cultures, two (2.2%) were positive for the pneumococcus, whereas of 240 infants with positive blood cultures, three (1.25%) grew pneumococcus. The incidence of maternal pneumococcal sepsis was 0.04/1000 live births, and that of the neonates, 0.06/1000, and the overall rate for sepsis in these two groups was 1.7 and 4.7/1000 live births, respectively. In three mother-infant pairs, the identical pneumococcal serotypes, 7, 18, and 23, were isolated from both mother and infant. Birthweights and gestational ages of the infants ranged from 2330 to 3730 gm and 34 to 40 weeks, respectively. Respiratory distress and poor peripheral perfusion were the predominant clinical signs in the infants with sepsis and became apparent from shortly after birth until 5 days of life. Pyrexia, poor general condition, and leukocytosis characterized the mothers with sepsis. All patients survived following antibiotic and supportive care. Our epidemiologic survey confirms the rareness of perinatal pneumococcal infection and the ability of these organisms to cause morbidity in both mothers and infants. PMID- 8442789 TI - Trisomy 21 presented as a transient unilateral pleural effusion at 18 weeks' gestation. AB - We describe a rare case in which a unilateral fetal pleural effusion was noted at 18 weeks' gestation with subsequent spontaneous resolution occurring 1 week later. Amniocentesis revealed a trisomy 21 karyotype. Chromosomal analysis may be indicated in cases in which accumulation of fluid in fetal serous cavities has spontaneously resolved. PMID- 8442790 TI - Elective suture of uterine cervix in triplets. AB - The incidence of triplet pregnancies has increased several times due to the widespread use of ovulation induction agents. Premature delivery is the main complication of triplet gestations. In twin conceptions it was shown definitely that elective cervical suture does not prolong these pregnancies. However, in higher order multifetal gestations the uterus is extremely overdistended and the application of cerclage is equivocal. This work intended to assess the value of elective cervical sutures in prolonging triplet pregnancies. Twelve of 35 women with triplet conceptions hospitalized at our high-risk pregnancy unit underwent an elective cerclage at 12 to 14 weeks and 23 women served as control subjects. None of them had any history or physical findings of cervical incompetence prior to the procedure. The gestational age (weeks) at delivery was 33.0 +/- 5.1 and 34.7 +/- 2.8 (mean +/- SD) for the sutured and noncerclage groups, respectively. The birthweight (grams) of the neonates was 1833.0 +/- 524.5 and 1884 +/- 455.5 (mean +/- SD) for the cerclage and nonsutured women, respectively. It seems that triplet gestations as such do not benefit from an elective cervical suture. PMID- 8442791 TI - Outcome of pregnancy in diabetic ketoacidosis. AB - To evaluate the outcome of pregnancy in diabetic women who had an episode of ketoacidosis during gestation, 20 consecutive cases of ketoacidosis in type I diabetic pregnant women were studied. They were divided into two groups for comparison: Group 1, 13 patients (65%), had a live fetus and group 2, seven patients (35%), had a fetal death on admission. Both groups were similar in age, gravidity, parity, abortions, height, weight, serum sodium and potassium, arterial pH, carbon dioxide tension, bicarbonate, base excess, and anion gap. Significantly different between groups 1 and 2 were: gestational age (24 versus 31 weeks; p < 0.05), serum glucose (374 versus 830 mg/dl; p < 0.005), blood urea nitrogen (14 versus 23 mg/dl; p < 0.025), osmolality (295 versus 311 mmol/kg; p < 0.025), insulin requirements (127 versus 202 U; p < 0.05), and length of resolution (28 versus 38 hours; p < 0.05). Two patients had serum glucoses less than 200 mg/dl despite profound ketoacidosis. Precipitating factors included infections, poor compliance, and very importantly, unrecognized new onset of diabetes (6 patients). All stillborns were grossly normal and those autopsied had no discernible cause of death. There were no maternal deaths. A high fetal mortality (35%) was found but there were no fetal losses once therapy was initiated. The unrecognized new onset diabetics accounted for almost a third (30%) of the cases of ketoacidosis and for 57% of the fetal deaths. Attentiveness to the symptoms of uncontrolled diabetes and appropriate screening can be effective preventive measures. PMID- 8442792 TI - Placental abruption following placement of disposable intrauterine pressure transducer system. AB - There have been few reported complications of intrauterine pressure monitoring. We present four cases of placental abruption following insertion of a disposable intrauterine pressure transducer system (INTRAN). All four patients had placental abruptions, which were evident soon after insertion of the disposable intrauterine pressure transducer system (all of our cases had predisposing factors or signs of placental abruption at presentation). Whether there was a preexisting placental abruption, which was caused, revealed, or worsened by insertion of the disposable intrauterine pressure transducer system is unclear. We encourage careful patient selection with gentle insertion of the system opposite the placental site. PMID- 8442793 TI - Indomethacin in severe twin-to-twin transfusion syndrome. AB - Despite advances in maternal fetal medicine, the management of severe twin-to twin transfusion syndrome in the second trimester presents a significant challenge. Presently, there is no uniformly accepted management protocol that is available for the treatment of this syndrome. We report the use of indomethacin in three cases of severe twin-to-twin transfusion syndrome in the second trimester. In the three cases of severe twin-to-twin transfusion syndrome no reduction of amniotic fluid in either sac was demonstrated. Two cases were complicated by single intrauterine fetal death within 72 hours of initiating indomethacin therapy. Because of our experience with these three cases, we conclude that indomethacin does not prevent perinatal mortality in patients with severe twin-to-twin transfusion syndrome. PMID- 8442794 TI - Mode of ascertainment is critical in assessing safety of percutaneous umbilical blood sampling. AB - Percutaneous umbilical blood sampling (PUBS) is increasingly utilized for cytogenetic assessment of the fetus. In the present study, outcome of 109 PUBS derived fetal blood samples were analyzed according to mode of ascertainment: ultrasound-detected anatomic anomalies or intrauterine growth retardation (IUGR). Abnormal chromosome complements were found in 6 of 47 (12.8%) fetuses with anomalies but in only 1 of 62 (1.6%) fetuses with IUGR alone. Perinatal loss in fetuses with anatomic anomalies was 64.4%, compared with only 1.6% in fetuses with IUGR alone. Mode of patient ascertainment is an important factor that must be considered in determining procedure-related risks for PUBS. PMID- 8442795 TI - Influence of maternal factors on cord and neonatal plasma micronutrient levels. AB - The influence of gestational length, maternal prenatal supplement and maternal levels on umbilical cord and neonatal plasma selenium, alpha-tocopherol, and retinol were studied and appropriate reference intervals for ongoing studies of gestational and perinatal micronutrient requirements were derived. We measured retinol, alpha-tocopherol (total and alpha-tocopherol:cholesterol ratio), selenium, and glutathione peroxidase in 160 umbilical cord samples and 58 paired maternal and neonatal samples collected on the third postpartum day. Selenium and glutathione peroxidase were also measured in 25 paired umbilical artery and vein samples. The strongest correlation with gestational age and birthweight was found for the cord blood variables, whereas levels in maternal blood were not related to either gestation or weight. Neonatal values were significantly lower than maternal for selenium (0.96 [0.25] compared with 1.56 [0.27] mumol/liter), retinol (0.54 [0.19] and 1.26 [0.45] mumol/liter), alpha-tocopherol (11.5 [3.63] and 32.4 [9.20] mumol/liter), and glutathione peroxidase (446 [174] and 873 [176] U/liter) but not for the ratio of alpha-tocopherol:cholesterol (5.0 compared with 6.0). Maternal use of tocopherol and retinol supplements did not significantly affect blood concentrations. Maternal plasma selenium levels at term were about 60% of nonpregnant adult females. Selenium concentration and glutathione peroxidase activity did not differ between paired umbilical cord arterial and venous samples. Selenium, retinol, and glutathione peroxidase differed between infants born before or after 37 weeks' gestation. PMID- 8442796 TI - Neonatal tricuspid insufficiency with abnormal tricuspid valve treated with extracorporeal membrane oxygenation (ECMO): possible extension of ECMO use. AB - Extracorporeal membrane oxygenation is now an accepted method of treatment for neonatal hypoxemia due to a number of causes. We extend the indications of ECMO to hypoxemia secondary to dysplastic tricuspid valve. We report the case of a neonate with congenital dysplastic tricuspid valve who responded to ECMO. PMID- 8442797 TI - Diagnosis and management of catheter-related infected intracardiac thrombosis in premature infants. AB - Infected right atrial thrombosis is an uncommon but severe complication of the use of central indwelling catheters in children. Massive thrombi around a right atrial catheter were seen in two critically ill premature infants after 3 weeks of parenteral nutrition. A catheter-related sepsis had previously occurred and had been treated by antibiotics. Subsequently, protracted thrombocytopenia, fluctuating hepatomegaly, and increasing respiratory distress were found in both cases. A right atrial mass was detected by 2 dimensional echocardiography. Cardiotomies for removal of the infected thrombus were performed with success in both cases. In one infant, weighing only 900 gm, surgical removal was accomplished with the aid of inflow stasis. Premature infants with catheter related sepsis appear at greater risk for intracardiac thrombosis and should undergo echocardiography as part of their evaluation. Infected atrial thrombi can be safely removed by cardiotomy even in the very small premature infant. PMID- 8442798 TI - Value of amnioinfusion in reducing meconium aspiration syndrome. AB - Infusing normal saline into the uterine cavity, or amnioinfusion, is used to reduce the risk of meconium aspiration syndrome in babies born to women in whom the pregnancy is complicated by thick, meconium-stained amniotic fluid. In this retrospective review of 436 such pregnancies amnioinfusion was performed in 110. In 18.2% of infants in the amnioinfusion group meconium was found in the trachea compared with 29.1% of infants in the untreated group. In the treated group respiratory distress occurred in 2.7%, and meconium aspiration syndrome in 1.8%, whereas in the untreated group these frequencies were 10.1 and 5.5%, respectively. We conclude that saline amnioinfusion in pregnancies complicated by thick, meconium-stained amniotic fluid reduces the risk of respiratory distress in the newborn. PMID- 8442799 TI - Developmental trends in fetal habituation to vibroacoustic stimulation. AB - Habituation is a measure of the ability to inhibit responding and is a more mature form of behavior than is persistent responding. We examined the developmental trend in habituation of the fetal startle response to repeated vibroacoustic stimulation in 90 normal human fetuses between 28 and 40 weeks of gestation. Fetal movement was graded according to the nature of the behavioral response: general startle (3), fast limb movement (2), slow rolling movement (1), and no movement (0). A significant developmental difference (p < 0.0004) in the rate of habituation was found, with response decrement occurring faster in fetuses of more than 32 weeks of gestation. Furthermore, by dividing the patients into three gestational age groups, it was determined that the greatest change in the rate of habituation occurred between 28 and 32 weeks and 32 and 36 weeks. We conclude that the rate of fetal habituation may be determined by the degree of maturation of the neural circuitry governing this form of nonassociative learning. PMID- 8442800 TI - First trimester disulfiram exposure: report of two cases. AB - Disulfiram has been used effectively to deter alcohol consumption in patients with a history of alcohol abuse. Its use in reproductive age women has become increasingly common in recent years, intensifying the risk of fetal exposure. Nonspecific but significant abnormalities have been described in the infants of women treated with disulfiram in the first trimester of their pregnancies. Based on these data, authors have previously exposure is confirmed despite a lack of any pattern to the defects reported. We report the outcomes of two pregnancies with first trimester disulfiram exposure. In both cases, the timing and dose of disulfiram was known. In one case, disulfiram was the only potential teratogen exposed to the fetus. Both neonates were normal at birth and have shown subsequent normal development. This report suggests that the poor prognosis previously given to fetuses exposed to disulfiram in the first trimester may not be warranted. PMID- 8442801 TI - Tension hemopericardium complicating neonatal pneumopericardium. AB - The case of a premature infant ventilated for hyaline membrane disease and complicated by recurrent tension pneumopericardium requiring surgical drainage is reported. The infant improved but developed a tension hemopericardium following the removal of the surgical drain. He had cardiac arrest, responded to resuscitation and drainage of the tension hemopericardium with a percutaneous catheter. At thoracotomy, a bleeding epicardial vessel was found and ligated. The infant survived and appeared to be normal at discharge. PMID- 8442802 TI - Echocardiographic assessment of systolic time intervals in vaginal and cesarean delivered neonates. AB - Echocardiographic assessments of fetal and neonatal systolic time intervals were made to determine differences in circulatory changes in 40 neonates delivered vaginally and 30 delivered by elective cesarean section. Left preejection period (LPEP), left ventricular ejection time (LVET), LPEP/LVET, right preejection period (RPEP), right ventricular ejection time (RVET), RPEP/RVET, and heart rate were determined at various time points from antenatal to 120 hours after delivery. There were no significant changes in left systolic time intervals between the two groups at any various time points. However, RPEP and RPEP/RVET values were significantly higher in the cesarean section group than in those in normal vaginal delivery group within 12 hours after delivery. These results suggest that the transient pulmonary hypertension after delivery is prolonged in babies delivered by elective cesarean section. PMID- 8442803 TI - Shigellosis in a newborn. AB - We report a case of neonatal shigellosis presenting with abdominal distention and shock. The literature on neonatal shigellosis is reviewed. Neonatal shigellosis should be included in the differential diagnosis of newborns presenting with shock and abdominal symptoms along with necrotizing enterocolitis, midgut volvulus, and intussusception. PMID- 8442804 TI - The Iowa premature breech trial. AB - A prospective, randomized clinical trial involving patients in premature labor (28 to 36 weeks' gestation) with breech presentation comparing 18 with immediate cesarean section with 20 with observed labor was undertaken at the University of Iowa from 1978 to 1983. The "observed labor" group had more deaths and lower Apgar scores (not statistically significant). Acidosis at delivery was not more common in the observed labor group, but 25% were delivered by cesarean section for fetal distress. The only neonatal deaths of nonanomalous babies, who were acidotic at delivery, occurred in patients who were managed outside of the trial, because delivery occurred soon after admission to the hospital. Congenital malformations accounted for one-third of the neonatal deaths; birth trauma did not occur in the 38 study patients. PMID- 8442805 TI - Prenatal sonographic diagnosis of isolated distal amelia of an upper extremity. AB - We report a case of fetal amelia (limb deficiency). The causes of this anomaly include amniocentesis, amniotic band syndrome, teratogen exposure, or a vascular accident. Recently, chorionic villus sampling has also been implicated in the amputation of an extremity. Although chorionic villus sampling (CVS) was not performed in our case, this possible association suggests subsequent sonographic scanning following CVS should include precise delineation of all fetal limbs. PMID- 8442806 TI - Normal blood gases in fetuses with absence of end-diastolic umbilical artery velocity. AB - Five fetuses with absent end-diastolic umbilical artery velocity had normal fetal acid-base status assessed by cordocentesis. Each fetus, despite widely differing pathologic conditions, deteriorated over the next several days. These cases confirm an earlier report of normal gases with absent umbilical artery end diastolic velocity. Normal blood gases on cordocentesis cannot provide extended reassurance in fetuses with absent end-diastolic velocity. PMID- 8442807 TI - Oropharyngeal teratomas: a clinicopathologic study of four cases. AB - Oropharyngeal teratomas (OPT) represent an uncommon congenital tumor with significant morbidity and mortality. Optimal management requires prenatal diagnosis. The clinicopathologic features of four OPT (one stillbirth, two livebirths, and one therapeutic abortion) are reviewed and compared with cases previously reported in the literature. Diagnosis, management, clinical outcome, and the natural history of the entity are discussed. PMID- 8442808 TI - Cytobrush versus swab endocervical sampling for the detection of obstetric chlamydial infection. AB - Timely detection and treatment of chlamydial infections during pregnancy is an important public health issue. Exfoliated, infected cells must be present for successful detection of endocervical infection. We compared samples obtained using a cytobrush versus a Dacron-tipped applicator swab for tissue culture isolation of Chlamydia trachomatis from the cervices of 605 pregnant women. The prevalence of chlamydial infection was 5.1%. Cytobrush and Dacron-tipped swab sampling were equally accurate; each detected 80% of all chlamydial infections identified. There were no clinically significant obstetric complications following cytobrush sampling. Bacterial contamination was present in one third more samples obtained using the cytobrush than those obtained using the swab (p = .0001). Culture-independent diagnostic methods such as immunoassays may be preferable for diagnosis of chlamydial infection when cytobrush samples are processed from such clinical specimens. PMID- 8442809 TI - Oxygen concentrations from self-inflating resuscitation bags. AB - The study was designed to determine the flow rate necessary to achieve adequate oxygen delivery from self-inflating resuscitation bags. When no reservoir was used the fraction of inspired oxygen (FiO2) was between 0.5 and 0.6 for all flow rates greater than 7 liters/min. When self-inflating bags with oxygen reservoirs were tested, the FiO2 showed a consistent increase with increases in the flow rate from 0 to 15 liters/min flow. A flow rate of 10 liters/min was required to deliver an FiO2 of at least 0.8. Individuals should become thoroughly familiar with the equipment they select for use. Most will find it necessary to provide an oxygen flow of at least 10 to 12 liters/min to provide an oxygen concentration of at least 80%. PMID- 8442810 TI - Antepartum prediction of pulmonary hypoplasia: an elusive goal? AB - Diagnosis of fetal pulmonary hypoplasia could be of great benefit to the obstetrician in the management of those pregnancies complicated by prolonged preterm ruptured membranes. Ultrasonography and magnetic resonance imaging were employed for fetal diagnosis of pulmonary hypoplasia and we were unable to predict accurately those fetuses with pulmonary hypoplasia using two different published ultrasound formulas. Moreover, magnetic resonance imaging appears not to offer any advantages over sonographic evaluation in the diagnosis of fetal pulmonary hypoplasia. PMID- 8442811 TI - Continuous intravenous morphine infusion in postoperative newborn infants. AB - The efficacy and safety of morphine sulfate was evaluated in 20 neonates requiring surgery. Following surgery, each subject received an intravenous morphine loading dose (50 micrograms/kg) followed by a continuous infusion (15 micrograms/kg/hr) for a minimum of 24 hours. Heart rate, respiratory rate, and blood pressure were frequently monitored during therapy. Blood samples were obtained following surgery and during and after morphine therapy for analysis of serum morphine and beta-endorphin content. A 12-hour urine collection was obtained 12 hours following the start of the constant morphine infusion for analysis of morphine content. The mean (+/- SD) duration of morphine infusion was 34 +/- 15 hours and a steady-rate serum morphine concentration was 39 +/- 23 ng/ml. The respective serum morphine half-life, elimination rate, and volume of distribution were 6.6 +/- 2.9 hr, 0.126 +/- 0.056 hr-1, and 5.0 +/- 6.8 liters/kg. The mean percentage of unchanged morphine recovered in the urine was 39 +/- 19 of the dose administered over 12 hours. A significant reduction in serum beta-endorphin content was observed following the onset of morphine therapy. No adverse reports were noted that could be attributed to morphine therapy. Continuous morphine therapy appears to be effective in controlling neonatal postoperative pain, as suggested by subjective nursing observations and decreased serum beta-endorphin content. PMID- 8442812 TI - Risk factors and deliveries associated with preterm, severely small for gestational age fetuses. AB - Maternal and fetal risk factors and deliveries associated with 153 singleton, preterm, severely small for gestational age (SGA) fetuses were compared to the corresponding data of 153 next-born preterm appropriate for gestational age (AGA) fetuses matched for gestational age. Maternal history of previous delivery of an infant of SGA status, pre-eclampsia, hypertension without proteinuria, oligohydramnios, and fetal congenital anomalies were identified as risk factors for preterm, severely SGA deliveries. In the preterm, severely SGA group the rate for abdominal deliveries was 82%. Of these operations, 40% were emergency cesarean sections, many of which involved pre-eclampsia cases. If congenital malformations were excluded, perinatal mortality rate was 7% in the preterm SGA group and 4.6% in the preterm AGA group. Preterm, severely SGA fetuses constitute a perinatal risk group, which cannot be avoided. However, awareness of and familiarity with the risk factors associated with preterm, severely SGA cases can better equip the attending physician to consider appropriate perinatal care options. PMID- 8442813 TI - Commentary on Surface tension of therapeutic surfactants as evaluated by standard methods and criteria--Scarpelli, David, Cordova, and Mautone. PMID- 8442814 TI - Late postpartum eclampsia at 20 weeks' gestation. PMID- 8442815 TI - Endoscopic carpal tunnel release: an anatomic study. AB - Endoscopic carpal tunnel release has been shown to decrease postoperative recovery time in patients undergoing surgery for carpal tunnel syndrome. There is, however, some controversy concerning the safety and reliability of the procedure. We performed endoscopic carpal tunnel release utilizing the two portal technique described by Chow on 20 fresh cadaver specimens. There were no injuries noted in any of the vital structures including the ulnar artery, superficial palmar arch, third common digital nerve or flexor tendons. The transverse carpal ligament was found to be completely transected in 95% of the specimens. Hyperextension of the wrist significantly displaces the vital structures both dorsally and distally. The use of a slotted cannula and specially designed blades protect the surrounding structures during the procedure. Based on this study, endoscopic carpal tunnel release using the technique described by Chow may be performed reliably without injury to any of the vital structures. PMID- 8442816 TI - Arthroscopic restoration of depressed tibial plateau fractures using bone and hydroxyapatite grafts. AB - Depressed tibial plateau fractures in 13 patients were treated under arthroscopic control. In 3 patients, bone autograft was used; in the remaining 10, hydroxyapatite (HAP) grafts were used. The depression of the articular surface was managed by elevation of the subchondral plate through a small window. Assisted by fluoroscopy, we corrected and performed the grafting under arthroscopic control. Follow-up periods averaged 5 years 6 months for the autograft and 18 months for the HAP grafts. At the conclusion of the follow-up period, x-ray radiographs and computed tomography (CT) scan showed no evidence of arthrosis and knee motion was normal. There were no significant differences between the two groups. The interporous spaces showed new bone formation on closed biopsy 6 months postoperatively. PMID- 8442817 TI - Pull-out strength of five suture anchors. AB - Five commercially available suture anchor devices were tested to failure in human cadaveric proximal tibiae. A total of 198 trials were completed. Insertion was uncomplicated for all anchors, with the exception of the Acufex Rod TAG device, with five of 22 (23%) of these breaking upon insertion into thicker cortical bone. Overall, the anchors performed significantly (p < 0.05) better when placed in thicker cortical bone, further away from the joint surface, and when loaded in a direction parallel to the bone surface. The Mitek GII anchor failed (pulled out of bone) less often than the other anchors (19% vs. 46%). In loading perpendicular to the bone surface, the Mitek GII and Statak were the strongest (p < 0.05), with mean loads at failure of 82.5 and 90.2 N, respectively. The Acufex Rod TAG, Acufex Wedge TAG, and Mitek GI failed at 67.2, 65.5, and 49.4 N respectively. PMID- 8442818 TI - Steroid-related bilateral osteonecrosis of the patella. AB - We present a case of bilateral osteonecrosis of the patella in a patient during steroid therapy and demonstrate the radiological, arthroscopic, and histological features. Osteonecrosis of the patella should be considered as a possible cause of knee pain in patients receiving steroid therapy. PMID- 8442819 TI - A snapping wrist due to a loose body. Arthroscopic diagnosis and treatment. AB - A cartilaginous loose body of the radiocarpal joint was removed arthroscopically in a 45-year-old woman who complained of locking and snapping of her wrist. The diagnosis was made at arthroscopy and immediate relief was obtained. PMID- 8442820 TI - Treatment of transverse fractures of the patella by arthroscopic percutaneous pinning. AB - Successful management of displaced transverse fractures of the patella is accomplished using an arthroscopically assisted technique. The morbidity is markedly reduced, i.e., surgery is usually same day and recuperation is accelerated. PMID- 8442821 TI - Arthroscopic assisted internal fixation of volar intraarticular wrist fractures. AB - Open reduction internal fixation of displaced volar intraarticular distal radius fractures traditionally require sacrificing the volar ligaments to visualize the articular surface. We present a modification of standard arthroscopy that facilitates visualization of the radiocarpal joint while preserving these ligaments. PMID- 8442822 TI - Guidelines for privileges in arthroscopic surgery. AB - This report sets forth flexible guidelines to be used by hospitals or surgery centers to define privileges in arthroscopic surgery. The Arthroscopy Association of North America recognizes that the completion of a residency program, fellowship training, or hands-on workshop does not, per se, guarantee competence in arthroscopic surgery. The demonstration of an applicant's technical and motor skills by direct observation is a vital component of the credentialing process. Threshold criteria of state licensure, completion of surgical residency training, documentation of prior experience, and existing orthopaedic surgical privileges are defined. Levels of complexity of arthroscopic procedures are divided as basic and advanced. PMID- 8442823 TI - Arthroscopic fenestration of the olecranon fossa in the treatment of osteoarthritis of the elbow. AB - A new arthroscopic approach to the treatment of elbow osteoarthritis that permits debridement of the elbow joint together with the removal of intraarticular loose bodies is described. Twelve patients (11 male, one female) with an age range of 29-64 (mean 47.5 years) underwent the procedure. Post-surgery all patients had relief of elbow-locking and experienced a reduction in elbow pain (follow-up 3-30 months, mean 16 months). The technique is offered as a treatment option for patients with elbow osteoarthritis. PMID- 8442824 TI - The anterior labroligamentous periosteal sleeve avulsion lesion: a cause of anterior instability of the shoulder. AB - Recurrent anterior unidirectional instability of the shoulder is not always associated with a classic Bankart lesion, which is an avulsion of the anterior labroligamentous structures from the anterior glenoid rim. Because the anterior scapular periosteum ruptures, the labrum and the attached ligaments are found to float out anterior to the glenoid rim when viewed arthroscopically. The anterior labroligamentous periosteal sleeve avulsion (ALPSA) of the supporting anterior inferior ligamentous and labral structures of the shoulder joint was found in four of eight acute primary anterior shoulder dislocations. This lesion differs from the Bankart lesion because the anterior scapular periosteum does not rupture, thereby allowing the labroligamentous structures to displace medially and rotate inferiorly on the scapular neck. These lesions eventually heal, and lead to recurrent anterior dislocations because of the subsequent incompetence of the anterior inferior glenohumeral ligament. An arthroscopic technique that converts the ALPSA lesion to a Bankart lesion and subsequently reconstructs the supporting anterior inferior structures of the shoulder has been successful in 26 cases (4 acute and 22 chronic) which were followed for > or = 2 years. Only one dislocation occurred, and it was the result of severe trauma. PMID- 8442825 TI - The GLAD lesion: another cause of anterior shoulder pain. AB - A GLAD (glenolabral articular disruption) lesion is caused by a forced adduction injury to the shoulder from an abducted and external rotated position; patients with GLAD lesions present with anterior shoulder pain as their chief complaint. No signs of anterior instability are found on physical examination or at surgery. All cases are relieved of anterior shoulder pain by lidocaine injection intraarticularly during the arthrographic examination, but arthrographic examinations are normal. At surgery, a superficial anterior inferior labral tear has been identified in all cases associated with an anterior inferior glenoid articular cartilage injury. Arthroscopic debridement of the labral tear with glenoid articular chondroplasty or abrasion arthroplasty is the treatment of choice. All symptoms were eliminated within 3 months after the surgical debridement in all cases. PMID- 8442826 TI - Arthroscopic inferior capsular shift for multidirectional instability of the shoulder: a preliminary report. AB - Ten consecutive patients with involuntary multidirectional instability who did not respond to rehabilitative treatment were managed by an arthroscopic modification of the inferior capsular shift procedure described by Altcheck and Warren. All patients were reviewed 1-3 years postoperatively using both the satisfactory/unsatisfactory system of Neer and the Bankart rating scale of Rowe. The average Bankart score was 90 (range 75-95) and all patients had a satisfactory result according to the Neer system. The arthroscopic capsular shift procedure appears to provide satisfactory results in the management of selected patients with multidirectional instability as evidenced in this preliminary report. PMID- 8442828 TI - Principles and decision making in meniscal surgery. AB - This article provides a review of the basic science and clinical information available to the orthopedist on which a systematic approach to meniscal surgery can be based. Attitudes toward the meniscus have changed dramatically in the last 50 years. Laboratory investigations show that the menisci participate in many important functions, including tibiofemoral load transmission, shock absorption, lubrication, and passive stabilization of the knee joint. Histologic/structural analyses reveal the menisci to be annular structures, with the ability to transmit and properly distribute load over the tibial plateau, primarily facilitated by the circumferential collagen fibers in the peripheral third of the meniscus, in conjunction with their strong bony attachments at the anterior and posterior horns. Biologic studies demonstrate that meniscal healing can occur through two pathways: an intrinsic ability of the meniscal fibrochondrocyte to migrate, proliferate, and synthesize matrix (provided they are given the proper environment), and extrinsic stimulation through neovascularization (when the meniscal injury occurs in the vascular periphery). This review makes it clear that the menisci are essential components of the normal knee, and that techniques intended to preserve the menisci are both possible and mandatory. As evidence has accumulated from both animal and clinical studies of the frequent development of degenerative changes following meniscectomy, surgeons have become increasingly aggressive in their efforts to conserve as much meniscal tissue as possible. Current approaches to treatment of meniscal tears are based on a thorough understanding of meniscal structure, biology, and function, as well as familiarity with the basic principles of meniscal repair and resection. To synthesize these principles, the article concludes with an algorithm intended to guide surgeons in decision making when faced with a variety of meniscal lesions in different clinical situations. PMID- 8442827 TI - Arthroscopic decompression of shoulder impingement secondary to Os acromiale. AB - Os acromiale is the result of failure of one of the outer ossification centers of the acromion to unite with the more medial portion. This creates an additional motion segment which may itself contribute to impingement syndrome of the shoulder or which may create hypertrophy or spurs which directly impinge on the cuff. Three cases of impingement syndrome of the shoulder with associated os acromiale are presented. All three were initially relieved with arthroscopic subacromial decompression of either the entire os acromiale or simply of the impinging spur. After 1 year, however, all three had recurrent or continued complaints of pain and/or impingement. Therefore, it would appear that arthroscopic subacromial decompression is not a solution to impingement syndrome secondary to os acromiale. Careful preoperative radiographic evaluation to rule out all causes of impingement syndrome including os acromiale is essential so that the surgeon may better choose an approach to decompression. PMID- 8442829 TI - Arthroscopy of the elbow for removal of loose bodies. AB - Thirty-four patients had one or more loose bodies in the elbow that were extracted arthroscopically in 33, with a small arthrotomy in one. The pain was improved in 85% of patients, locking in 92%, and swelling in 71% of the patients. The number of flexion contractures was reduced from 14 to 5. However, crepitus was improved in only 47% of patients. Overall, 89% of patients had significant improvement by the arthroscopic procedure. There were two transient symptoms of numbness of the forearm but no permanent complications. Overall, arthroscopic removal of loose bodies from the elbow was a successful procedure, and the posterior portals should be used in all cases. PMID- 8442830 TI - The effects of knee effusion on quadriceps strength and knee intraarticular pressure. AB - The purpose of this study was to determine the effect of varied amounts of effusion on quadriceps strength and knee intraarticular pressure (IAP) during active knee movement. Five subjects had 60 ml of saline, in 20 ml increments, infused into the right knee. Quadriceps strength and knee IAP were continuously measured at each level of effusion, while the subject performed isokinetic knee exercises. A control group of five subjects performed the same exercises, but with no saline infusion. No significant changes in quadriceps strength were seen in the control group. In the experimental group, quadriceps strength decreased as the amount of effusion increased, and increased following aspiration. The greatest decrease in strength occurred at those knee positions where IAP was highest (full flexion and extension). Results of this study indicate that quadriceps strength is diminished and IAP markedly increased when an effused knee is exercised. PMID- 8442831 TI - Functional anatomy of the posterolateral structures of the knee. AB - The major supporting structures of the posterolateral knee were noted to be composed of three components: the fabellofibular ligament, the arcuate ligament, and popliteus muscle with origin from fibular head. We classified this area of the knee into seven major anatomic variants. Popliteus tendon is composed of two parts: the anterior and the posterior fibers. The anterior fibers become tight, while the posterior fibers become lax as the knee was flexed. This phenomenon is more pronounced when the tibia is rotated externally. The midpoint between the anterior and the posterior fibers insertions on the femur appeared to be the isometric point of the popliteus tendon. PMID- 8442832 TI - Arthroscopically assisted proximal extensor mechanism realignment of the knee. AB - An arthroscopically assisted proximal extensor mechanism realignment procedure has been designed and performed on 27 knees in 24 patients. The study group has been followed a minimum of 18 months. The procedure consists of a lateral retinacular release and an arthroscopically controlled plication of the medial patellar retinaculum and oblique fibers of the vastus medialis. The indications for this procedure include recurrent patellar instability and acute initial patellar dislocation with a concomitant fracture of either the patella or lateral margin of the intertrochlear sulcus. Using a simple subjective rating system for the patellofemoral joint, 25 of the 27 knees (92.5%) were subjectively rated good or excellent by the patient. Objective criteria also indicated a high success rate. There were two recurrent subluxations. There were two relatively minor complications. The average time for return to full presurgical activities, including previous sports, was 4 months. PMID- 8442833 TI - Repair and reconstruction of the ACL: is it good enough? PMID- 8442835 TI - Fixation strengths of patellar tendon-bone grafts. AB - Secure fixation of bone-patellar tendon-bone grafts is essential to allow early joint mobilization after anterior cruciate ligament (ACL) reconstruction surgery. This study was designed to evaluate four fixation methods of patellar tendon-bone grafts in cadaveric knees. Fifty-one fresh cadaveric patellar tendon-bone specimens were anchored in tibial or femoral metaphyseal bone tunnels. Group I grafts were fixed with Kurosaka interference screws. In Group II the grafts were initially fixed as in Group I, but the screws were then removed, the bone plugs repositioned, and the grafts resecured with screws. In Group III the grafts were anchored with three no. 2 nonabsorbable sutures tied over a screw and washer, whereas in Group IV no. 5 nonabsorbable sutures were used. Each bone specimen was mounted in the biomechanical testing machine, and a vertical tensile load was applied at a strain rate of 51 cm/min until failure of fixation, bone plug fracture, or tendon disruption occurred. The mean force to failure in Groups I, II, III, and IV were 435.0 N, 458.2 N, 454.2 N, and 415.8 N, respectively. There was no significant difference in the force to failure among the four methods of fixation. However, the modes of failure were diverse. In three specimens the Kurosaka screws diverged from the plugs and failed to achieve fixation. These specimens were excluded and will be discussed separately. Although technique related difficulties may arise, interference screw fixation of patellar tendon bone grafts affords strong graft fixation--often stronger than the graft itself. Secondary screw fixation appears to be equal in strength to primary screw fixation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8442834 TI - Miniarthrotomy versus arthroscopic-assisted anterior cruciate ligament reconstruction with autogenous patellar tendon graft. AB - The purpose of this study was to determine whether two groups of patients showed any early (6 months postoperative) clinical differences when treated by arthroscopic-assisted or miniarthrotomy anterior cruciate ligament (ACL) reconstruction. Fifty-two consecutive arthroscopic-assisted ACL reconstructions (Group I) were matched with 52 miniarthrotomy ACL reconstructions (Group II). An autogenous midthird patellar tendon was used in all reconstruction procedures. Group I patients were operated on by one surgeon (A.C.R.) and all Group II patients by another (K.D.S.). Both groups were similar with regard to age, sex, injury, chronicity, and previous knee surgical procedures. All patients were treated according to the same postoperative rehabilitative protocol (emphasizing early motion, immediate full passive extension, early functional activity) and evaluated on follow-up by the same personnel and protocol. Data collection included injury and surgery dates; total surgery and tourniquet times; length of hospital stay; drain output; inpatient pain medications used; follow-up range of motion at 1.5, 2.5, and 6 weeks postoperative; KT-1000 arthrometer measurements at 10, 16, and 26 weeks; and isokinetic measurements at 10 and 16 weeks postoperative. Results indicated that follow-up range of motion and KT-1000 measurements showed no statistical difference between groups. Isokinetic average scores for quadriceps strength at 180 degrees/s showed no differences at 10 and 16 weeks. The study suggested that ACL reconstruction with midthird patellar tendon performed by skilled surgeons using either open or arthroscopic-assisted techniques combined with an aggressive postoperative rehabilitation protocol will yield similar acceptable early clinical results. PMID- 8442837 TI - A comparison of patient-controlled analgesia and continuous lumbar plexus block after anterior cruciate ligament reconstruction. AB - Anterior cruciate ligament (ACL) reconstruction is often a painful operation. Fifty-eight patients who underwent ACL reconstruction using patellar tendon autograft received either a lumbar plexus block (LPB) or patient-controlled analgesia (PCA) for pain relief during the first 24 h after surgery. The average total dose of narcotic used was dramatically less for the LPB group (10.1 mg) than for the PCA group (91.9 mg). The common narcotic analgesic side effects of nausea, pruritus, sedation, and urinary retention were significantly less in the LPB group. The LPB is a safe and effective alternative analgesia after ACL reconstruction. PMID- 8442836 TI - The induction of IL-1 by freeze-dried ethylene oxide-treated bone-patellar tendon bone allograft wear particles: an in vitro study. AB - There have been recent reports of adverse clinical results with freeze-dried ethylene oxide-treated bone-patellar tendon-bone (FD-ETO-BPTB) allografts used in anterior cruciate ligament (ACL) reconstruction. Ethylene oxide and its residues were implicated as the cause of many of the failures. Wear particles generated from both freeze-dried ethylene oxide-treated and deep frozen bone-patellar tendon-bone (DF-BPTB) allografts were placed in culture with lapine synoviocytes. The resulting synovial-conditioned media were then assayed for interleukin-1 (IL 1) content. IL-1 is a potent mediator of tissue inflammation. FD-ETO-BPTB wear particles generated statistically significant levels of IL-1 when compared with both a negative control and DF-BPTB wear particles. PMID- 8442838 TI - Intraarticular capacity and compliance of stiff and normal elbows. AB - The capacity, compliance, and position of minimum intraarticular pressure were measured in eight stiff and 10 normal elbows of 11 patients before corrective surgery for posttraumatic elbow joint contracture. Capsular compliance was determined from the slope of the pressure/volume relationships. The capacity of the normal elbow joint capsule was 14 +/- 2, whereas that of the stiff elbow was 6 +/- 3 ml. The capsular compliance of the stiff elbow was only 15% of normal, confirming that the capsule is structurally altered and not just contracted. Adequate capsular distension of the stiff elbow might therefore not be possible, increasing the potential for neurovascular injury with use of the anterior portals in elbow arthroscopy. The position of minimum intraarticular pressure and maximum compliance ("resting position"), of the normal elbow was 70 degrees. If the elbow is left immobilized in this position for an extended period of time, the risk of posttraumatic elbow joint capsule contracture might increase. This agrees with our finding that the stiff elbows had a preoperative arc of motion of 70-120 degrees and a significantly diminished capsular capacity relative to normal. PMID- 8442839 TI - Beneficial impact of epidural anesthesia on recovery after outpatient arthroscopy. AB - The ideal outpatient anesthetic provides analgesia, is readily reversible, has minimal complications, and allows for a prompt hospital discharge. Iatrogenic side effects, such as nausea/vomiting and pain, however, may hamper patient recovery and delay discharge. The influence of anesthesia [general (G) versus epidural (E)] was assessed in 260 patients (G = 181, E = 79) undergoing ambulatory knee arthroscopic surgery. Patients were studied before discharge and on follow-up (24 h) to evaluate the effect of the anesthetic technique. Discharge times were shorter in the E group (159 +/- 6 min SEM E, compared with 208 +/- 8 min SEM G), as was the incidence of pain (24.1% versus 49.7%), and nausea/vomiting (8.9% versus 32%) before discharge. Patient satisfaction was equal in the two groups. Our study shows that in select patients, epidural anesthesia is a viable alternative to general anesthesia for knee arthroscopy, offering the advantages of fewer side effects and earlier discharge times. PMID- 8442840 TI - Effect of varying laser parameters on pulsed Ho:YAG ablation of bovine knee joint tissues. AB - We investigated the effect of varying laser parameters on ablation of fresh bovine knee joint tissues (fibrocartilage, hyaline cartilage, and bone) with a free-running Ho:YAG laser. Ablation rate was measured in saline for each tissue type as a function of laser fluence (160-950 J/cm2), pulse width (150-450 microseconds, full width at half maximum), and fiber core diameter (400 and 600 microns). A weight that was attached to the fiber end was used to exert a constant pressure of 40 g/mm2 to the tissue underneath to ensure a constant contact between the fiber tip and the tissue throughout the ablation process. All tissues could be efficiently ablated, and the ablation rate increased linearly with the fluence. Change in laser pulse width and fiber core diameter resulted in minor variations in the ablation rate for fibro- and hyaline cartilage. On the other hand, use of longer pulses and/or the larger fiber significantly accelerated bone ablation. Histology analysis revealed that zones of thermal damage in Ho:YAG irradiated bovine knee joint tissues differed by tissue types and ranged between 100 and 400 microns, but were independent of fluence, pulse width, and fiber size within the range tested. PMID- 8442841 TI - Drug utilization studies. Methods and uses. Introduction. PMID- 8442842 TI - The economic aspects of drug use. PMID- 8442843 TI - Health authorities and drug utilization studies. PMID- 8442845 TI - Consumers as instigators and users of drug utilization research. PMID- 8442844 TI - Drug utilization and the health professions. PMID- 8442846 TI - Drug utilization and the teaching of rational drug use. PMID- 8442847 TI - Drug utilization studies: their transferability between industrialized and developing countries. PMID- 8442848 TI - From clinical trials to drug utilization studies. PMID- 8442849 TI - Therapeutic formularies, essential drugs, drug utilization studies. PMID- 8442850 TI - General background. PMID- 8442851 TI - Descriptive tools and analysis. PMID- 8442852 TI - The quantification of drug risks in practice. PMID- 8442853 TI - The social aspects of drug use. PMID- 8442854 TI - A new pair of surface molecules involved in human IgE regulation. AB - The molecules controlling IgE production are the subject of intense study in the effort to find new ways to treat allergic diseases. One candidate, the CD23 molecule, a low affinity receptor for IgE, was recently identified to interact with another molecule, named CD21, in the regulation of IgE production. PMID- 8442855 TI - Multiple levels of peripheral tolerance. AB - The establishment and maintenance of self tolerance is based on multiple events in the thymus and periphery, resulting in either deletion of self-reactive T cells or induction of nonresponsiveness. Here, Bernd Arnold and colleagues propose that, depending on the tolerogenic signals, peripheral T cells can reach different levels of tolerance with regard to their capacity for reactivation. In addition, it appears that tolerant T cells are still susceptible to further tolerogenic signals, driving them into a deeper state of tolerance. Thus, induction of T-cell tolerance can be viewed as a multistep mechanism. PMID- 8442856 TI - Towards a comprehensive view of immunoglobulin class switching. AB - While it is well established that T cells play a prominent role in regulating Ig isotype switching in response to T-cell-dependent (TD) antigens, the events which control this process in response to antigens that do not recruit antigen-specific T cells (T-cell-independent (TI) antigens) is less clear. In this article, Clifford Snapper and James Mond suggest that the nature of the B-cell activator, in combination with cytokines produced by antigen non-specific cells, including macrophages, NK cells, and polyclonally activated B cells, may play an important role in the process leading to Ig isotype switching in response to TI antigens. PMID- 8442857 TI - Colony stimulating factors, cytokines and monocyte-macrophages--some controversies. AB - In the literature concerning induction of monocyte-macrophage inflammatory mediators in vitro by colony stimulating factors, IFN-gamma and TGF-beta, there are many conflicting observations; likewise there is disagreement when the regulation of the synthesis of colony stimulating factors by cytokines is examined. Here, John Hamilton attempts to identify unifying concepts from the conflicting data. He goes on to discuss the experimental variables that have led to the current confusion and to assess the significance of the in vitro studies to physiology and pathology. PMID- 8442858 TI - Lymphocyte lifespans: homeostasis, selection and competition. PMID- 8442859 TI - The dynamic relationship between B-cell populations in adults. PMID- 8442860 TI - MHC research: fast forward. AB - Study of the major histocompatibility complex (MHC) has rarely been more exciting or fruitful than at present. New HLA genes are regularly being discovered, and the elucidation of molecular structure and antigen presentation at the molecular level continues apace. These, and the emerging contribution of MHC analysis to molecular anthropology and to the study of evolution, were addressed at a recent workshop. PMID- 8442861 TI - The turnover of B-cell populations. PMID- 8442862 TI - Lymphocyte survival and V-region repertoire selection. PMID- 8442863 TI - B-cell lifespans in the mouse--why to debate what? PMID- 8442864 TI - Observations on constitutional resistance to infection. PMID- 8442865 TI - The coming of age of cancer radioimmunoconjugates. AB - Great progress in imaging and therapy with radioimmunoconjugates was discussed at the fourth conference on radioimmunodetection and radioimmunotherapy of cancer. Monoclonal antibody-based cancer imaging agents are awaiting marketing approval and newer, potentially improved forms are in development. Tumor responses to radioimmunoconjugates are also being reported in increasing numbers, this is especially so with radiosensitive tumors and in regional or direct applications. PMID- 8442866 TI - [The use of a biosynthetic human growth hormone in children with a growth hormone deficiency]. AB - Ten growth hormone deficient patients (GHDP) (six girls & four boys) with chronological age range six-15 years old, received recombinant human growth hormone (GH) (0.6 UI/kg/week) in three subcutaneous injections per week over 14 months. A complete physical examination was performed monthly; thyroid hormones concentrations every two months, as well as, bone age every four months were determined. Growth velocity was higher in the first six months' treatment (12.73 +/- 1.65 cm/yr vs 10.6 +/- 1.67 cm/yr; previous growth velocity 3.76 +/- 2.4 cm/yr). The variables with better prognosis were: lower previous growth velocity, lower chronological age (< 12 ys), lower bone age (< 8 ys), higher BMI than ideal; and higher acid alkaline phosphate during treatment. Two of ours patients developed biochemical hypothyroidism during the treatment period, and they needed hormonal substitutive therapy. With GH treatment a harmonious growth is obtain with bone age progress according chronological age. The height of GHDP treated with GH do not approaches the height range of their parents, probably due the time of treatment. In the follow-up of all patients treated with GH is important to realize periodical laboratories screenings looking for another hypothalamic and/or hypophyseal deficiencies. PMID- 8442867 TI - [The prevalence and risk factors of cleft lip and cleft palate in 2 hospitals in the city of Guadalajara, Jalisco, Mexico]. AB - OBJECTIVE: The purpose of this article is to determine the prevalence of the cleft lip and palate and its association with some risking factors. MATERIAL AND METHODS: A retrospective, observational and analytic study, of 44 newborn infants with cleft lip and palate and their controls, in 33,461 consecutive births, with 20 weeks or more, and birth weight more than 500 g, since November of 1988 to June of 1991. The information were obtained from the database of the Congenital External Malformation Register, done by the University of Guadalajara, in four hospitals. The prevalence of the cleft lip and palate was calculated. Of the variables studied their association was searched with congenital malformation in 2 x 2 tables, calculating, its chi square, confidence interval, and old ratio. RESULTS: The prevalence of the cleft lip and palate was of 13.2 x 10,000 births. By categories: cleft lip 2.7 x 10,000, cleft lip and palate 7.8 x 10,000 and cleft palate 2.7 x 10,000. The only statistics differences with control group were the association with antecedent of other malformation in the family and methrorrague during pregnancy. CONCLUSIONS: The found prevalence is similar to the one informed in the literature, with some differences by categories. The association with antecedent of another malformation in the family, support the role of the hereditary role in the multifactorial etiology. PMID- 8442868 TI - [The use of thoracic radiography in a third-level-care pediatric hospital]. AB - OBJECTIVES: 1. To describe the frequency in which the thorax radiography is requested in a third-level pediatric hospital, 2. To identify the frequency of detected abnormalities in such a study by the radiology service, 3. To describe the frequency and the characteristics form the information considered as useful in a clinical way, not only in the radiography application but in the radiologic report and the clinical file as well, 4. To identify the frequency in which the thorax radiography result is associated with diagnosis changes and/or therapeutic ones. DESIGN OF THE INVESTIGATION: Descriptive survey. STUDY UNITS: 371 thorax X rays completed during December 1990 and January 1991. PRIMARY RESULTS: The thorax radiographies were 32% of the entire radiological study during the survey; 335 of the latter ones (90%) were requested for inpatients. The hospital services which had the highest request for such a study were the Intensive Care Unit (n = 149, 40%) and Medical Pediatrics (n = 116, 31%). The most frequent diagnosis leading to the application was pneumonia (n = 55, 15%) and solid neoplasia (n = 51, 14%). Three-hundred forty eight of the applications had diagnostic impression given by the physician in charge(94%); whereas only 127 (34%) mentioned clinical data. The radiology report was attached to the file in 162 (44%) of the cases. It was found that form the patients who had a radiology report and the thorax radiography as an initial study (n = 95), 48 (50%) suffered from abnormalities. The results of the study were transcribed in the file in 58 cases (16%); the physician's interpretation was written down in 229 cases (62%) and in 84 studies (23%) there was no reference to the results of the study (P < 0.0001). Changes in the therapeutic plan of 93 cases (50%) were identified from the studies with official report by the radiologist, other radiology studies were requested in 65 of the patients (35%), after the interpretation of such study. CONCLUSIONS: Abnormalities in 50% were identified from the total thorax radiographies requested as the patient entered. The study application mentioned as a whole (94%) the diagnostic impression which led to the application, but only in 127 cases (34%) were supporting clinical data written down. The radiology report was attached to the file in less than half the cases (44%). In 63% of the cases the supporting reason of the study was written down whereas in 23% there was no reference to the result at all. PMID- 8442869 TI - [Hepatic hemangioma in a premature newborn. The magnetic resonance images]. AB - Hepatic hemangiomas are benign vascular tumors that represent 5-15% of all liver tumors. They occur more often in females than in males (relation 2:1). They may produce cardiac failure, because of high output; less frequently hemolytic anemia, thrombocytopenia or bleeding are observed. We present a case of a newborn premature child with a gestation age of 34 weeks and weight of 1359 g who presents a palpable abdominal tumor in the right hypochondrium without additional symptoms. The diagnosis was confirmed by ultrasound with Doppler system any by means of the magnetic resonance imaging (MRI) both methods were able localize the hemangioma in the posterior segment of the right hepatic lobulus. MRI is a diagnostic tool which can provide finer anatomic details than ultrasound or axial computed tomography in hepatic hemangiomas. MRI has a sensitivity of 90% and specificity of 92%; the treatment depends of the complications which the patient presents. PMID- 8442870 TI - [Diaphragmatic paralysis due to a lesion of the phrenic nerve secondary to venesection at the neck for parenteral feeding]. AB - It is presented the clinical record of a female newborn of 39 weeks of gestational age, with birth weight of 4600 g, with diaphragmatic palsy eight days after birth. Were realized diaphragmatic plicature and the clinical course was without any complication. Were reviewed the causes of diaphragmatic palsy and was described the relationship, with vein cannulation for parenteral nutrition. PMID- 8442871 TI - [The treatment of status epilepticus in children]. AB - In children the status epilepticus (SE) constitutes a neurological emergency related to a high rate morbi-mortality. The prompt recognition and management are essentially to prevent irreversible neurologic damage. The frequency of SE in emergency rooms and pediatric intensive care units (PICU) is high because of several causes in the group of children less than five years old and particularly in the first year of life. In this paper are analyzed the actual state of drug therapy, general management and prevention of complication to decrease the incidence of severe sequelae in this patients. We suggest a general guide for the pediatrician and intensivist that include monitoring in a PICU for permanent valuation of the patient which result in a better treatment to improve the outcome and survival. PMID- 8442872 TI - [The differential diagnosis of poliomyelitis and other acute flaccid paralyses]. AB - Between June 1988 to January 1991 a total of 246 children with acute flaccid paralysis (AFP) were seen at Hospital Infantil de Mexico, Federico Gomez which was the center of study for AFP for the Poliomyelitis Eradication Program of Mexico. Of the 246 children, 42 has poliomyelitis (17%); 156 has Guillain-Barre syndrome (GBS) (63.4%); 16 had traumatic neuritis of the sciatic nerve secondary to IM injections (TNC) (6.5%); five had transverse myelitis (2%); the rest (27) had other diseases misdiagnosed as polio (10.9%). The basic clinical characteristics for the diagnosis of poliomyelitis are: myalgias and fever at the onset AFP, paralysis is asymmetrical, of distal predominance and causes severe muscular atrophy and skeletal deformities; the GBS presents as an ascending, symmetrical, areflexic paralysis of distal predominance. It does not causes atrophy or deformities. TNC presents several days after IM injections with pain and hypothermia in the affected limbs; TM is a flaccid, symmetrical paraparesis with neurogenic bladder and a sensory level. CSF and neurophysiological studies (EMG and NCV) are very useful for diagnosis. Other entities misdiagnosed as poliomyelitis were: osteoarticular trauma, myopathies and dystrophies, viral myositis, acute cerebellitis, retroperitoneal tumors and upper motor neuron syndromes. Viral studies in stool specimens are essential for the diagnosis of poliomyelitis. PMID- 8442873 TI - [The usefulness of the polymerase chain reaction (PCR) in research and clinical diagnosis in pediatrics]. AB - Recent advances in molecular biology for the first time make possible the widespread application of this science for the diagnosis and clinical investigation of pediatric disease. One very important discovery has been the development of the polymerase chain reaction. This technique allows for the exponential amplification of specific DNA sequences producing quantities sufficient for the molecular diagnosis of a wide variety of diseases. We review some of the fundamental aspects of this technique as well as some of its most promising applications in the field of pediatrics. PMID- 8442874 TI - [The use of antibiotics in a community of Mexico City. I. A household survey]. AB - Based on previous community-oriented studies an irrational use of antibiotics, particularly in developing countries, has been suggested. In order to describe the pattern of antibiotic use in a periurban community in Mexico City, 1659 randomly selected households were visited and an interview to the housewife was carried out. Of 8279 individuals 425 (5%) had used at least one antimicrobial in the preceding two weeks. Main perceived reasons for drug use were: respiratory tract ailments (58%) and acute diarrhea (25%). Antibiotic therapy was given in 27% of respiratory diseases and in 37% of all diarrheal episodes. Most commonly used drugs were: penicillins (43%), erythromycin (13%), metronidazole (9%), neomycin (6%), cotrimoxazole (6%) and tetracyclines (6%). While self-medication was common (19%) the majority of antibiotics were prescribed by a physician (81%). Approximately two thirds of individuals using an antibiotic did it for less than five days. Our data suggest a frequent misuse of antibiotics and support the future assessment, in this community, of physician prescribing practices, the determinants of self-medication as well as the impact of this drug use on the selection of resistant bacterial strains. PMID- 8442875 TI - [Epigenetic changes in the expression of a functional protein in the brain induced by gestational malnutrition]. PMID- 8442876 TI - [Schonlein-Henoch purpura. A report of 55 cases]. AB - The clinical, histological and laboratory data from a series of 55 pediatric patients with Henoch-Schonlein purpura studied at the Hospital General de Mexico in a 16-years period are presented herein. Even when there are a few clinical features in this example of Mexican children, the clinical presentation and the course of the disease are similar to what is found in the literature. PMID- 8442877 TI - [Antibiotic consumption in a community of Mexico City. II. Survey of purchases at pharmacies]. AB - In developing countries, antibiotics are the most common sales of drugs and it has been suggested that their irrational use leads to the emergence of resistant bacteria. In order to assess the purchase of antimicrobials in a peri-urban community in Mexico City six local drug stores were randomly selected. A social worker made five visits to each pharmacy and she observed the events during the purchase of the drug and applied a structured questionnaire to the customer immediately after the transaction. Antibiotics were the majority (29%) of the drug sales. Of all purchasers of an antibiotic 43% did it without medical prescription and 72% answered that a physician had influenced on the purchase. Duration of the antibiotic therapy was specified in one out of three prescriptions that were examined and only in 28% of the sales the purchase was enough for a treatment duration of more than four days. More information, from similar surveys in drug stores in other settings, is needed to support the reinforcement of actions to control the sales of antibiotics in the community. PMID- 8442878 TI - [Prevalence of enteropathogenic bacteria in children with acute bloody diarrhea]. AB - Between January to October 1991, were studied 148 samples of feces corresponding to the same number of children with acute diarrhea. In 41 (27.7%) samples, were found macroscopic or microscopic blood. At least one associated bacterial pathogen capable to produce bloody diarrhea was isolated from 22 (53.7%) of these samples. Were isolated five (12.2%) Salmonella strains, all of them were S. enteritidis; nine (22.0%) Shigella: seven S. flexneri, one S. boydii, and other one S. sonnei; two (4.9%) enteroinvasive Escherichia coli strains, and six (14.6%) Campylobacter jejuni strains. A single associated invasive bacterial pathogen was isolated in 13 (31.7%) children. Mixed culture were found in nine children: five (12.2%) children had invasive pathogens association, and four (9.8%) children had invasive and no invasive pathogens association. PMID- 8442879 TI - [Candida endocarditis in the first year of life]. AB - Candida is an increasing problem as a causal agent of nosocomial infection in neonates and infants. We report 15 cases of infective endocarditis caused by Candida spp treated at the Hospital Infantil de Mexico between 1980 and 1991. The diagnosis of endocarditis was established by the identification of Candida in at least two blood cultures and echocardiographic assessment. From 110 cases of systemic candidiasis during the eleven years period of study, fifteen patients presented endocarditis (13.6%), all had a central venous catheter. Three had antecedent of congenital heart disease. Candida isolation was obtained an average of 28 days after admission. The major clinical findings were: fever in 13 patients, respiratory distress and cardiac murmurs observed in nine respectively. Thrombocytopenia was present in eight children. The echocardiographic evaluation showed vegetations located in the superior vena cava in six, right atrium in five, tricuspid valve in two, inferior vena cava and right ventricle in one respectively. Three cases were subjected to surgical treatment. Nine patients died for a case fatality rate of 60%. The echocardiographic evaluation practiced in all patients with suspicion of systemic candidiasis is critical for the prognosis. The identification of endocardiac involvement coupled with the opportune administration of antifungal therapy and surgical treatment may improved the survival. PMID- 8442880 TI - [Utilization of percutaneous catheters in neonatology: insertion of 105 catheters]. AB - We present the results of one prospective study made it to evaluated central percutaneous catheters morbi-mortality in newborns critically sick ingresed in a Neonatal Intensive Care Unit (NICU). The total of 105 percutaneous catheter put it on in 97 newborns from one total 1554 catheter-days. We found in 53.3% were premature newborns, 74.2% weighted less than 2500 g, the femoral veins was used in 90%. The predominant morbidity at the moment of the colocations was respiratory problems, sepsis and mayor congenital malformation, the 30% the percutaneous catheter was had bacterial colonization when were retired; the catheter infection was 1.2 x 1000 catheter days. Our conclusion are the percutaneous catheter was the prime election to the vein access in the newborn critically stick, with low mortality rate during colocation and permanency, low sepsis incidence by catheter, and less quantity of venopunture stress and veins mutilation. PMID- 8442881 TI - [Biochemical and hematometric effects of exchange transfusion in isoimmunized neonates]. AB - A hundred twenty full term newborns infants (RN) with ABO or Rh isoimmunization who were submitted to exchange transfusion (ET) because hyperbilirubinemia have been studied and with the procedure were demonstrated: 1. Increase the levels of serum sodium in 2.8% in the RN of ABO group and 3.2% in the RN of Rh group with a recurrence of the original values prior to the procedure within three hours post ET. 2. The levels of serum sodium equal or superior to 180 mEq/L (mmol/L) in the donor's blood led to hypernatremia after the ET, with a recurrence of the original values prior to the procedures within three hours post-ET. 3. The levels of serum potassium of the RN decreased (-7.7% in the ABO group and -5.47% in the Rh group) with a recurrence of the normal values in the control of six hours post ET in the ABO group and one of 12 hours in the Rh group. 4. The levels of total calcium in the controls haven't been significantly altered up to 24 hours post ET. 5. Regarding the pH, in spite of having used blood with low levels compared to those expected for fresh blood, the RN for this experiment maintained the acid base balance within normal range. In relation to the hematimetric values, the ET: 1. Increase both hemoglobin (Hb) and hematocrit (Hto) values in both groups (increase of 5.6% in Hb and 6% in Hto in the ABO group and increase of 9.2% in Hb and 6.1% in Hto in the Rh group), right after the ET, with a reduction in the control posterior to that. 2. The values of Hb and Hto were always inferior in the RN in the Rh group. Therefore, it has been shown the high intensity of the hemolysis in this group. PMID- 8442882 TI - [Selective IgA deficiency and malabsorption. Review of the literature apropos of a case]. AB - One of the most common primary immunodeficiencies is the selective deficiency of IgA, which is present in very variable clinical conditions. This situation had conducted to different criteria with respect to the clinical meaning in a particular patient. The association of immunodeficiency of IgA and intestinal malabsorption is reported as statistically significant in the international literature. Nevertheless, the precise pathogenic connection between them is unknown. The relationship between bowel and immune system is reviewed here, and illustrated with the clinical case of a six-year old girl who presented with malabsorption and selective deficiency of IgA. PMID- 8442883 TI - [Diaphragmatic hernia, secondary to a phrenic nerve lesion, in a newborn infant]. AB - The diaphragmatic eventration will be congenital or acquired; the damage to the phrenic nerve its for elongenest, cruch, gun ball or iatrogenic; this last one could be during cardiac surgery, birth trauma, venodissection and colocation of one thorax drill. We presented the case of one premature newborn of 32 weeks with 1374g of weight, with respiratory distress syndrome which evolutioned to bilateral pneumothorax and posteriorly left diaphragmatic eventration secondary to a phrenic nerve damage by the thorax drill which one reach to mediastinum. The diagnosis of these entity will suspect by abnormal elevation of the affected hemidiaphragm and confirmed by fluoroscopy. The treatment its a early diaphragmatic pleat. PMID- 8442884 TI - [Trisomy 5p due to paternal translocation (4;5) (q35;p12)]. AB - A ten month-old boy had a 5p trisomy secondary to a paternal t(4;5) (p35;p12) translocation. The main stigmata were macrocranium, hydrocephaly, coloboma of the right iris, atrial septal defect, talipes equinovarus, and psychomotor retardation. Overall, the clinical picture was characteristic of the 5p trisomy that includes the band 5p13. PMID- 8442885 TI - [Medical writing and scientific style]. AB - I contrast here the qualities of scientific style with the actual vices of medical writing. Besides, the grammatical tense and the concept of author in scientific literature are also briefly reviewed. PMID- 8442886 TI - Lowering of blood ethanol by activated carbon products in rats and dogs. AB - Earlier studies on the effects of activated carbon (charcoal) on blood alcohol levels (BAL) in animals have been conflicting. The present study was designed to study the effects of a commercially available product (Charcoaid) and a new patented product (Alcosorb), in capsules and in suspension on the BAL of rats and dogs. We compared peak BAL and the regression of BAL with time during ethanol clearance in rats given 1.5 g/kg of carbon products in sorbitol intragastrically, followed 5 min later by 3.5 g/kg ethanol intragastrically. Peak BAL were significantly higher after Charcoaid 1 h after intubation, compared to Alcosorb and sorbitol (vehicle for the charcoal suspension). A study in which ethanol was given intraperitoneally instead of intragastrically showed no differences in ethanol BAL produced by the intragastric carbon treatments. In a crossover study using Beagle dogs, 780 mg capsules of carbon products ("low dose") given 5 min before ethanol had no significant effect on BAL. A "high" dose of 20 g of charcoal products suspended in water, followed by ethanol intragastrically, was also ineffective in lowering blood ethanol. However, carbon products suspended in a water/ethanol vehicle (20% w/v) did significantly lower peak BAL. We conclude that carbon products significantly lower BAL in rats and dogs, and that in rats, Alcosorb and sorbitol produce a greater BAL lowering effect than Charcoaid for a brief time after administration. The mechanisms of the BAL lowering effect by sorbitol and charcoal products are probably different. PMID- 8442887 TI - Dose-dependent effects of prenatal ethanol exposure in the guinea pig. AB - The guinea pig is an appropriate animal for studying ethanol central nervous system (CNS) teratogenesis due to its extensive prenatal CNS development. In order to establish an ethanol dosage regimen that produces CNS teratogenesis, the objective of this study was to characterize the dose-dependent effects of chronic ethanol administration on pregnancy outcome and locomotor activity of the offspring. Pregnant guinea pigs received one of the following oral treatments, via intubation into the oral cavity, throughout gestation: 3, 4, 5 or 6 g ethanol/kg maternal body weight/day; isocaloric sucrose and pair feeding; or water. The 5 and 6 g ethanol/kg/day regimens produced maternal death, spontaneous abortion, and perinatal death with at least 75% incidence; the 3 and 4 g ethanol/kg/day regimens produced little or no maternal, embryonic/fetal, or perinatal lethality. The 3 and 4 g ethanol/kg/day regimens did not affect other indices of pregnancy outcome compared with the respective isocaloric-sucrose pair fed control animals and water-treated animals. The 3, 4, and 5 g ethanol/kg/day regimens increased spontaneous locomotor activity in the offspring, and there was a direct relationship between the magnitude of hyperactivity at days 10 and 60 of age and each of the ethanol dosage regimens and the maternal blood ethanol concentration on day 56 of gestation. The data demonstrate that, in the guinea pig, chronic oral administration of ethanol produces: (a) dose-dependent effects on pregnancy outcome, (b) hyperactivity in the offspring that is dose- (and maternal blood ethanol concentration-) and age-related, and (c) persistent hyperactivity into adulthood with minimal toxicity on pregnancy outcome for the 4 g ethanol/kg/day regimen. PMID- 8442888 TI - Irreversible suppression of alcohol drinking in cyanamide-treated rats after sustained delivery of the 5-HT2 antagonist amperozide. AB - The purpose of this study was to evaluate the long-term effect of sustained treatment with amperozide, which has been shown to attenuate the volitional drinking of ethyl alcohol in the rat without side effects. Preference for alcohol first was induced pharmacologically in Sprague-Dawley rats by the inhibitor of aldehyde dehydrogenase, cyanamide, administered in a dose of 10 mg/kg twice daily for 3 days. Then following a standard preference test, each rat was offered water and its maximally preferred concentration of alcohol which ranged from 7% to 15%. Following a 4-day pre-drug test, saline control vehicle or amperozide was administered for 7 days by an osmotic minipump implanted in the intrascapular space. A single dose of 208 micrograms/kg/h (i.e., 5.0 mg/kg/day) was selected on the basis of a prior dose response study of amperozide. During the interval of sustained release of amperozide, the consumption of alcohol declined significantly in terms of both absolute g/kg intake and proportion of alcohol to water. When the preference of the rats was retested at 4, 30, 70, 110, and 140 day intervals after the pump had exhausted amperozide, the absolute g/kg consumption of alcohol continued to decline significantly. Unlike other drugs, amperozide did not produce any side effects, particularly on the intake of food or water or on body weight, which suggests a pharmacological specificity of its action.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8442889 TI - Tetrahydropapaveroline in brain regions of rats after acute ethanol administration. AB - Tetrahydropapaveroline (THP), the condensation product of dopamine, and its aldehyde, dopaldehyde, have been detected in brain regions of rats after acute ethanol administration. THP levels were determined in eight brain regions of animals that received ethanol (3.0 g/kg) by intraperitoneal injection 100 or 120 minutes before decapitation. The levels of THP in two brain regions, i.e., the midbrain and striatum, were determined at time intervals ranging from 50 to 120 minutes after ethanol administration. THP was not found in brain regions of untreated animals. However, significant levels of THP were found in pooled midbrains (0.50 pmol/g tissue) and pooled hypothalami (0.20 pmol/g tissue) of animals that received ethanol 120 minutes before decapitation. Most brain regions had detectable levels of THP 100 minutes after the animals received ethanol and the striatum contained the highest concentration of the alkaloid. The concentration of THP in striata tissue of rats at 50, 70, 90, or 100 minutes after ethanol administration were 0.33, 0.38, 0.33, and 0.33 pmol/g tissue, respectively. These results demonstrate that THP can be detected in specific brain regions of the rat after acute ethanol administration. PMID- 8442890 TI - Ethanol self-administration by alcohol-nonpreferring (NP) rats in a continuous access situation. AB - Male rats, from the alcohol nonpreferring (NP) line, were studied in operant chambers in which food pellets, water, and 10% ethanol (v/v) were available continuously for 23 h/d. The NP rats consumed less ethanol per day following 7 weeks under these conditions than did either alcohol-preferring (P) rats or Long Evans (LE) studied previously under the same conditions for 4 weeks. The NP rats consumed 0.2 g/kg per day during the first week of the experiment, 0.72 g/kg per day during the fourth week, and 1.03 g/kg per day during the seventh week compared to 2.2 g/kg per day for LE rats and 4.8 g/kg per day for P rats following 4 weeks. These data indicate that NP rats will slowly initiate ethanol self-administration under continuous access conditions, but to a lesser extent and at a slower rate than other lines of rats studied previously. PMID- 8442891 TI - Changes in hepatic collagen produced by chronic intoxication of rats with ethanol. AB - It was decided to study the effect of chronic intoxication of rats with ethanol on collagen content in the liver, its solubility, and molecular polymorphism. It was found that treatment of rats with 10% ethanol instead of drinking water for 6 months resulted in a 50% increase of collagen content in livers of the investigated animals. Significant changes in quantitative relationships between types I, III, and V collagens were observed. Proportional amounts of type III and V collagens were higher and type I collagen was lower in comparison to those in control rat liver. PMID- 8442892 TI - Effects of prenatal alcohol exposure on uncoupling protein in brown adipose tissue in neonatal rats. AB - Thermoregulatory deficits observed in neonatal rats exposed prenatally to alcohol may be due to peripheral and/or central dysfunction. One of the major mechanisms available to newborn mammals to generate heat is "nonshivering thermogenesis" in brown adipose tissue (BAT). In this study, the effects of prenatal alcohol exposure on the functional status of brown adipose tissue was assessed by immunoblot analysis of the content of mitochondrial uncoupling protein (UCP). BAT excised from 1- and 20-day-old male and female offspring from either alcohol treated, pair-fed controls or standard control dams were analyzed. There were no effects of prenatal alcohol exposure on the UCP content. There was, however, a significant increase due to age. These results suggest that thermoregulatory deficits seen in alcohol-exposed offspring are not due to a deficiency in the concentration of mitochondrial UCP, and indicate a more central mechanism. PMID- 8442894 TI - Omega-conotoxin increases sleep time following ethanol injection. AB - omega-Conotoxin and ethanol produce similar actions on in vitro calcium channel functions. The present study was designed to determine their possible behavioral interaction. omega-Conotoxin injected ICV at either 0.1 microgram or 0.3 microgram, produced an increase in spontaneous and evoked tremor activity in male Sprague-Dawley rats. The tremor was present at 30 min and continued at least 4 h after injection. At 4 h post ICV injection, animals were given an IP injection of ethanol (3 g/kg body weight). Although no blood alcohol differences were observed between groups, rats injected with omega-conotoxin showed a concentration dependent increase in sleep times: Saline controls slept for an average of 84.7 +/- 16.7 min, 0.1 and 0.3 microgram conotoxin treated animals slept for 121.3 +/- 16.2 and 211.1 +/- 30.7 min, respectively. These results extend the class of calcium channel blockers capable of producing a behavioral interaction with ethanol. PMID- 8442893 TI - Prenatal alcohol exposure attenuates pentylenetetrazol-induced convulsions in rats. AB - Female rats prenatally exposed to alcohol were tested at 35 days of age for susceptibility to pentylenetetrazol (PTZ)-induced convulsions. There was a significant dose-response effect of PTZ. Contrary to expectations, alcohol exposed females were slightly but still significantly less convulsion-prone than pair-fed controls. These results suggest prenatal alcohol exposure reduces the susceptibility to convulsions in rats. PMID- 8442895 TI - Ethanol increases ADP-ribosylation of histones in rat hepatocyte nuclei. AB - Ethanol was shown previously to increase ADP-ribosylation of hepatocyte proteins. The purpose of this study was to determine the effect of ethanol on ADP ribosylation of histones in hepatocyte nuclei. Freshly isolated hepatocytes were exposed to 100 mM ethanol for 2 h and ADP-ribosylated histones were separated from nonribosylated histones by phenylboronate agarose chromatography. Both histone factions were then separated into the individual histones by 12% acetic urea-triton polyacrylamide gel electrophoresis. Ethanol did not change the amounts of outer histone H1 or amounts of core histones (H2A, H2B, H3.1, and H4) but increased the histone variants H3.2 and H3.3. The principal effect of ethanol was to increase the ADP-ribosylation of all the above histones. Exposure of hepatocytes in culture to 100 mM ethanol for 3 days did not increase the synthesis of histones as determined by the incorporation of 14C-L-lysine, but increased the ADP-ribosylation of histones, principally histone H2A, determined from the incorporation of 2, 8, 3H adenosine. These results show that ethanol increases the ADP-ribosylation of histones. This is a potential mechanism for effects of ethanol on the regulation of gene expression and cell differentiation. PMID- 8442896 TI - Electrophysiological and behavioral findings in rats prenatally exposed to alcohol. AB - Clinical studies have shown that behavioral and electrophysiological abnormalities occur in some human infants born to alcoholic mothers. The present study used rats to evaluate the effects of prenatal ethanol exposure on locomotor behavior and two paradigms for the generation of auditory event-related potentials (ERPs). Pregnant rats were fed liquid diets, one group received alcohol and the other was a nutritional control. The offspring were allowed to mature prior to the electrophysiological and behavioral testing. Prenatal alcohol exposed rats showed significantly more locomotor behavior in the first 4 hours of their activity cycle than nonethanol exposed rats, although not over a subsequent 8-hour period. Evaluation of the electrophysiological data revealed that the prenatal alcohol exposed group had significantly longer latencies of their P1 and N1 ERP components, in the hippocampus, than the control group. These results support anatomical data suggesting that the hippocampus may be an important area in which to direct further study of what brain mechanisms may be altered by prenatal ethanol exposure in the rat. PMID- 8442897 TI - Electrophysiological indices predict resumption of drinking in sober alcoholics. AB - Eighty-nine alcoholics and 54 nonalcoholic controls were tested on measures of late component event-related potentials (ERPs) using a visual "oddball" stimulus task. The alcoholics had just completed inpatient alcoholism treatment programs and were 21-45 days sober. Approximately 13 months later, subjects returned for retesting; alcoholics were classified as resumers or abstainers based on thier drinking patterns during the interest interval. Using the ERP measures from the initial testing session, alcoholics differed significantly from controls in the multivariate analysis and on P300 amplitude (P3A). Resumer alcoholics showed significantly longer N200 latencies (N2L) than abstainer alcoholics. Discriminant function analyses predicting resumer/abstainer status from N2L, P3A and N1A indicated a 63% prediction rate, chi 2 = 5.67, p < 0.02. Addition of N2L to previously tested psychological and social predictor variables indicated an increase in the amount of variance explained. The results support a biopsychosocial model for understanding and predicting relapse in chronic alcoholics. PMID- 8442898 TI - Species difference in sensitivity to ethanol's hedonic effects. AB - Recent research suggests that rats and mice differ in their sensitivity to ethanol's rewarding effect in the place conditioning paradigm. However, these species have not previously been examined in a comparable manner. The present study compared genetically heterogeneous rats and mice using an identical place conditioning procedure. Each animal received four pairings of a distinctive tactile floor stimulus with injection of ethanol (1.5 g/kg); a different tactile stimulus was paired with saline injection. Ethanol suppressed activity in rats but elevated activity in mice. As in most previous studies with drug-naive animals, rats showed aversion whereas mice showed preference for the ethanol paired stimulus. This difference cannot be attributed to differences in housing conditions, apparatus, stimuli, or temporal parameters. Rather, it appears to represent a species difference in initial sensitivity to ethanol's hedonic effects. If one assumes that ethanol is both rewarding and aversive, this outcome might be explained by a species difference in tolerance/sensitization, the time course of the biphasic hedonic response to a single ethanol exposure, or selective association. Together with other recent studies from this laboratory, the present findings suggest the mouse may well be the species of choice for studying preferences conditioned by ethanol. PMID- 8442900 TI - A novel use of the link-file system for longitudinal studies of HIV infection: a practical solution to an ethical dilemma. AB - BACKGROUND: Longitudinal studies that collect sensitive data, such as test results for HIV antibodies, present difficult ethical problems for investigators. Personal identifiers are needed for longitudinal follow-up, but current regulations in the United States require that all subjects be informed of their HIV test results when identifiers are retained. Therefore, subjects who do not wish to learn their HIV status must be excluded from prospective research. Because these subjects may be at particularly high risk for HIV infection, this situation may lead to substantial bias. METHODS: We describe a new application of a methodology for blinding such studies, based on the link-file system used for protecting subjects' sensitive research data. This design enables investigators to hold each subject's HIV test result and survey data for multiple ascertainments over time while effectively severing any link between this information and the subject's identity. This objective is achieved by a process of sequential coding, using at least two coders who are not associated with the study. CONCLUSIONS: The method described in this paper permits investigators in the United States to perform important prospective epidemiologic studies while adhering to current regulations for the conduct of such investigations. PMID- 8442899 TI - HIV infection and severe malnutrition: a clinical and epidemiological study in Burkina Faso. AB - OBJECTIVE: To define a clinical profile indicative of HIV infection in a population of severely malnourished children in Burkina Faso. A total of 433 children (average age, 19 months) were recruited at the Sanou Souro National Hospital, Bobo Dioulasso, Burkina Faso. RESULTS: Sixty-three per cent presented with marasmus, 13% with kwashiorkor and 24% with both forms of malnutrition. The prevalence of HIV infection in children aged over 12 months was 13.8%, with a marked predominance of HIV-1 (95.8%). Mother-to-child transmission was proven in 77% of the cases; in 10% of the observed paediatric AIDS cases, transmission may have occurred through multi-injections with contaminated equipment. Marasmus was the form of malnutrition most frequently associated with HIV (P < 0.001); its severity was exacerbated by HIV infection. Adenopathy (P < 0.0001), oral candidiasis (P < 0.0006), skin disorders (P < 0.01) and hepatomegaly (P = 0.01) appeared to be significantly related to HIV infection. Discriminant analysis revealed that the presence of adenopathies was the strongest indicator symptom of HIV infection. Multivariate analysis revealed that a clinical profile of marasmus, adenopathies and oral candidiasis (specificity, 82%) was indicative of HIV infection in this population. The short-term clinical prognosis was poor and usually led to the death of the child when seropositive (P < 0.001). CONCLUSIONS: Among children exhibiting severe malnutrition, HIV-positive children are distinguished by a high horizontal transmission rate, a high specific clinical profile and a very poor prognosis. PMID- 8442902 TI - 'What does the phrase "safer sex" mean to you?' Understanding among Glaswegian 18 year-olds in 1990. AB - OBJECTIVE: To ascertain what young people in western Scotland understand by the phrase 'safer sex', and the social correlates of this knowledge. DESIGN: Face-to face interviews with 18-year-olds participating in the third stage of a longitudinal study of the social patterning of health and illness. SETTING: The Central Clydeside Conurbation in western Scotland. PARTICIPANTS: Eight hundred and seventy-nine 18-year-olds (416 men and 463 women). MAIN OUTCOME MEASURES: Reported understanding of the term 'safer sex'. RESULTS: Eighty-four per cent mentioned condoms, 68% some aspect of choice of partner, and only 2% abstaining from specific sexual activities. Those in more advantaged socio-economic circumstances and with higher levels of education were more likely to have 'better' knowledge (defined as mentioning condom use plus one or more other risk reduction strategy). CONCLUSIONS: Although knowledge of the routes of transmission of HIV may be reasonably good among the young, knowledge of what professionals mean by 'safer sex' appears less so, particularly among the more deprived sections of the community. PMID- 8442901 TI - No connection between alcohol use and unsafe sex among gay and bisexual men. AB - OBJECTIVE: To investigate the relationship between alcohol use and unsafe sexual behaviour. METHODS: The paper discusses data collected from 461 gay and bisexual men interviewed in England and Wales by Project SIGMA during 1991-1992. These data were collected during face-to-face interviews using retrospective weekly diary techniques and include details of all sexual sessions and alcohol use. The 819 reported sexual sessions with other men are divided into those that involved alcohol use (30.6%) and those that did not. RESULTS: Differences in the incidence of HIV risk behaviours between sexual sessions that involved alcohol use and those that did not are small, and none are statistically significant. Furthermore, for those men who engaged in sexual behaviour whilst under the influence of alcohol, the quantity of alcohol consumed had no effect on sexual behaviour. CONCLUSIONS: Among gay and bisexual men, sex under the influence of alcohol is no more likely to be unsafe than sex among men who have not consumed alcohol. PMID- 8442903 TI - Administration of zidovudine during primary HIV-1 infection may be associated with a less vigorous immune response. PMID- 8442904 TI - Does zidovudine reduce tumour necrosis factor-alpha in HIV-positive patients? PMID- 8442905 TI - Effect of the oral anticoagulant, warfarin, on HIV-1 replication and spread. PMID- 8442906 TI - Dideoxyinosine-associated nephrotoxicity. PMID- 8442907 TI - Estimating HIV prevalence in Switzerland. PMID- 8442908 TI - Quantifying the risk of HIV-1 transmission via breast-milk. PMID- 8442910 TI - Human T-lymphotropic virus type I infections in western India. PMID- 8442909 TI - Anti-CD4 antibodies generated in response to HIV-1 rgp160 immunization of HIV-1 infected chimpanzees. PMID- 8442911 TI - Trichosporon beigelii fungaemia in an AIDS patient. PMID- 8442912 TI - Zidovudine half-life in haemodialysis patients. PMID- 8442913 TI - Toxoplasmic encephalitis during pregnancy. PMID- 8442914 TI - 5-Fluoro-uracil-clindamycin for treatment of cerebral toxoplasmosis. PMID- 8442915 TI - Patterns of immunoglobulin G subclass reactivity to HIV-1 envelope peptides in children born to HIV-1 infected mothers. PMID- 8442916 TI - HIV-1 strains from India are highly divergent from prototypic African and US/European strains, but are linked to a South African isolate. AB - OBJECTIVE: To gain molecular insights into different HIV-1 strains present in two different states of India, nucleotide sequences derived from the env region of four HIV-1 strains were analysed. DESIGN: HIV-1 was isolated from high-risk patients from the states of Maharashtra (city of Bombay) and Goa. The molecular analysis of the env region encompassed all variable domains of the external glycoprotein, gp120. METHODS: Genomic DNA from cultured cells infected with each of the four Indian HIV-1 strains independently was amplified by polymerase chain reaction (PCR). PCR fragments were cloned and sequenced and a phylogenetic tree constructed. RESULTS: All four Indian HIV-1 sequences were closely related to each other. The closest related sequence to them was from a South African isolate, HIV-1NOF, with a homology of 85-87%. In the phylogenetic tree, the Indian and the South African HIV-1 sequences cluster together and constitute a subtype different from the North American/European, Central African, Uganda/Rwanda and Northern Thailand subtypes. Interestingly, the viruses of this subtype are characterized by an additional potential N-glycosylation site C terminal to the CD4-binding domain. CONCLUSION: The low variation between the HIV 1 sequences from randomly chosen individuals from high-risk cohorts in two Indian states suggests a rapid and recent spread of HIV and, possibly, introduction of the virus by the same route, most probably heterosexual transmission. The rapid spread of HIV-1 variants in India, which form a subgroup of their own together with a South African strain, necessitate consideration of these strains in vaccine development. PMID- 8442917 TI - In vivo decrease in the expression of complement receptor 2 on B-cells in HIV infection. AB - OBJECTIVE: To investigate changes in the expression of complement receptor 2 (CR2) on B-cells from HIV-infected individuals. CR2 is the C3d/Epstein-Barr virus receptor and has been implicated in B-cell activation. Changes in its level of expression may therefore be associated with B-cell dysfunction. DESIGN: Cross sectional study of HIV-infected adults and age-matched control donors. METHODS: The percentage expression and mean fluorescence intensity of CR2 (and three additional markers: CD19, CD69, and a standard antigen designation: HLA-DR) was measured on CD20+ B-cells using a two-color flow cytometric assay. RESULTS: This study demonstrated a highly significant (P = 0.0001) decrease in the percentage co-expression of CR2 on CD20+ B-cells in HIV-infected individuals, compared with control donors. The mean percentage of CD20+ cells co-expressing CR2 was 71% (s.d., +/- 15%) in the HIV-seropositive patients and 94% (s.d., +/- 4%) in the control group. The pattern of CR2 expression in a number of the patients suggested a decrease in antigen density on the cells. Decreased expression of CR2 did not correlate with disease stage (asymptomatic, AIDS-related complex, or AIDS), nor with CD4+ T-cell percentage or absolute count, in the seropositive group. CONCLUSIONS: The evidence for a role for CR2 in B-cell activation suggests that its decreased expression, which we have demonstrated in HIV-seropositive individuals, may be associated with the B-cell dysfunction observed in HIV infection. Our finding that expression of this marker is decreased even in asymptomatic patients is consistent with reports of early B-cell defects in such individuals. Further investigation of this possible association may shed some light on both the increased incidence of bacterial infections in HIV-infected adults and children and their impaired responses to certain immunizations. PMID- 8442918 TI - Primary prophylaxis for Pneumocystis carinii pneumonia: a randomized trial comparing cotrimoxazole, aerosolized pentamidine and dapsone plus pyrimethamine. AB - OBJECTIVE: To compare the efficacy and tolerance of monthly aerosolized pentamidine versus cotrimoxazole versus dapsone plus pyrimethamine to prevent the initial episodes of Pneumocystis carinii pneumonia (PCP) in HIV-infected patients. DESIGN: An open randomized clinical trial. PATIENTS AND METHODS: HIV infected patients (n = 331) with CD4 cell counts < 200 x 10(6)/l or with AIDS but without a history of PCP or cerebral toxoplasmosis (CT) were randomized to receive pentamidine (300 mg every 4 weeks), cotrimoxazole (160/800 mg 3 days a week) or dapsone plus pyrimethamine (100 and 25 mg weekly). If immunoglobulin G (IgG) antibodies to Toxoplasma were present, patients in the first two groups were randomized further to 25 mg pyrimethamine per week or to no treatment. RESULTS: The mean follow-up was 313 days (range, 30-670 days). The three groups were homogeneous for age, sex, risk group for HIV infection, initial CD4 cell count and mean follow-up. PCP developed in 16 patients, with an estimated cumulative probability of 5.3% at 1 year of follow-up. The PCP rate per year of observation, using an intention-to-treat analysis, was 5.6% [95% confidence interval (CI), 0.9-10.3], 3% (95% CI, 0-6.3) and 8.3% (95% CI, 2.8-13.8) in the groups treated with pentamidine, cotrimoxazole and dapsone plus pyrimethamine, respectively (P > 0.05). Moderate or severe side-effects were observed in one patient on pentamidine, 10 on cotrimoxazole and nine on dapsone plus pyrimethamine (P < 0.05); the study drug had to be discontinued in no, 10 and six patients, respectively (P < 0.05). Neither cotrimoxazole alone nor pyrimethamine combined with dapsone or cotrimoxazole prevented initial episodes of toxoplasmosis among patients with IgG antibodies to Toxoplasma gondii. CONCLUSIONS: Low-dose thrice-weekly cotrimoxazole or weekly dapsone plus pyrimethamine was not significantly worse (differences > 15% would have been detected with 90% certainty) than monthly aerosolized pentamidine in preventing a first episode of PCP in patients at high risk, but aerosolized pentamidine was better tolerated. PMID- 8442919 TI - Efficacy and safety of rechallenge with low-dose trimethoprim-sulphamethoxazole in previously hypersensitive HIV-infected patients. AB - OBJECTIVE: This study was undertaken to determine whether patients infected with HIV and with prior hypersensitivity to trimethoprim-sulphamethoxazole (TMP-SMX) can be rechallenged successfully with TMP-SMX, what factors predict successful rechallenge, and whether hypersensitivity is due to TMP or to SMX. DESIGN: A prospective, open study. SETTING: A tertiary referral hospital. PATIENT: Thirty one HIV-infected patients with a history of non-life-threatening hypersensitivity to TMP-SMX. INTERVENTIONS: Patients received TMP (300 mg twice a week) for 2 weeks and, where no major reaction occurred, subsequently with TMP-SMX (160 and 800 mg per tablet, one tablet two times a day, twice a week). Patients who developed significant and persistent hypersensitivity ceased SMX and were subsequently challenged with TMP-dapsone (300 and 100 mg, respectively, twice a week). MAIN OUTCOME MEASURES: That rechallenge is more likely to be successful in those with advanced HIV disease. RESULTS: Five out of 31 (16%) patients developed hypersensitivity to TMP, and two ceased TMP as a result. Fifteen of the 26 (58%) patients who received subsequent TMP-SMX developed hypersensitivity, 12 of whom ceased TMP-SMX because of this reaction. Hypersensitivity to TMP-SMX was significantly less common in those with a CD4+ cell count < 20 x 10(6)/l than in those with a CD4+ cell count > 20 x 10(6)/l (31 versus 85%; P = 0.03). Hypersensitivity to TMP-dapsone occurred in two out of nine patients with hypersensitivity to TMP-SMX on rechallenge. One patient developed transient dyspnoea following a dose of SMX, but no other serious adverse drug reaction occurred. CONCLUSIONS: Rechallenge with TMP-SMX appears safe in HIV-infected patients with a history of non-life-threatening hypersensitivity and is most likely to be successful in patients with a low CD4+ lymphocyte count. The data suggest a low rate cross-hypersensitivity between SMX and dapsone, at least at the doses used. PMID- 8442920 TI - Pleural effusion, tuberculosis and HIV-1 infection in Kigali, Rwanda. AB - OBJECTIVE AND METHODS: An increasing number of diagnoses of pleural effusions (PE) have been made over the last 8 years in the Department of Internal Medicine of the Centre Hospitalier de Kigali, Rwanda. In order to determine the aetiology of PE and to examine its possible association with HIV-1 infection, we performed an aetiological work-up, including thoracocentesis and pleural punch biopsy, of all new patients with PE of undetermined aetiology referred to the Division of Pulmonary Diseases of the Department of Internal Medicine of the Centre Hospitalier de Kigali between 14 September 1988 and 16 October 1989. HIV-1 serological testing was performed for most of the patients. RESULTS: A total of 127 patients (81 men, 46 women; mean age, 34 years; range, 16-71 years) with PE of undetermined aetiology were enrolled. Pleural tuberculosis was diagnosed in 110 (86%) and confirmed histologically and/or bacteriologically in 90 (82%). Of 98 pleural tuberculosis patients tested for HIV-1-antibody, 82 (83%) were HIV-1 seropositive. Metastatic cancer was responsible for PE in six (5%) patients, Kaposi's sarcoma in three, lymphoma in one (all four HIV-1-seropositive), anaplastic carcinoma in one, and adenocarcinoma in one (both HIV-1-seronegative). Non-tuberculous pneumonia was documented in five (4%) patients and was associated with HIV-1 infection in four. Other causes of PE were congestive heart failure (three patients), decompensated cirrhosis (one), constrictive percarditis (one), or undetermined (one); only one of these patients was HIV-1-seropositive. CONCLUSIONS: We conclude that tuberculosis is the predominant cause of PE in our patients and is strongly associated with HIV-1 infection. Although less frequent, non-tuberculous pneumonia, Kaposi's sarcoma and lymphoma are other causes of HIV 1-associated PE. In an African area highly endemic for HIV-1 and Mycobacterium tuberculosis co-infection, PE should be considered a good marker of tuberculosis as well as HIV-1 infection. PMID- 8442921 TI - Q fever and HIV infection. AB - OBJECTIVE: To study the frequency of Q fever in HIV-infected individuals. DESIGN: A seroprevalence study. SETTING: French National Reference Centre for Rickettsial Agents, Marseille, France. PATIENTS AND METHODS: Five out of the 68 hospitalized cases of Q fever diagnosed in 1987-1989 were also HIV-infected and are described here. Sera from a blood-donor bank (n = 925) and from HIV-positive individuals selected at random, irrespective of clinical or immunological status (n = 500) were tested for Q fever. RESULTS: Comparisons of the two groups showed a statistically significant difference (2.4 versus 0.8%; Fisher's exact test) at the diagnostic dilution 1:200 and at the dilution considered positive for seroprevalence study (1:1000). CONCLUSIONS: Using the estimated incidence of HIV infection in Marseille, the number of Q fever cases in 1987-1989 was 13 times higher and the clinical expression more frequently symptomatic in the HIV positive population than in the general one. The prevalence:seroprevalence ratio for Q fever was 1.37% in the HIV-positive group and 0.36% in the blood-donor group. Sera positive for Q fever were confirmed by Western blot analysis in order to minimize cross-reaction. Transmission of Q fever appears to be more frequent in HIV-positive individuals than in the general population; this is not surprising, since Coxiella burnetii lives in the phagolysosome, like other micro organisms described in immunocompromised hosts. Q fever should be added to the spectrum of diseases that occur more frequently during HIV infection. PMID- 8442922 TI - Disseminated meningococcal infection in HIV-seropositive patients. AB - OBJECTIVE: Although increasing numbers of infections due to various bacterial pathogens have been described in HIV-infected individuals, there have been few reports to date of disseminated Neisseria meningitidis infections in such individuals. We describe here the presentation and clinical course of systemic meningococcal infection in two HIV-1-seropositive men and the response to meningococcal vaccine in one. DESIGN AND METHODS: Retrospective analysis of case reports of two patients identified in a municipal hospital in Denver, Colorado, USA, and evaluation by enzyme-linked immunosorbent assay of antibody response to quadrivalent (A, C, Y, W-135) meningococcal vaccine. RESULTS: A 27-year-old HIV seropositive man with bacteremic group Y meningococcal pneumonia and a 45-year old man with AIDS and group B meningococcal arthritis both responded to short term antibiotic therapy without recurrence. The second patient responded to meningococcal vaccination with seroconversion to all four serogroups. CONCLUSIONS: Disseminated meningococcal infection, although rare in HIV-infected individuals, may present with a variety of clinical manifestations and responds well to antibiotic therapy. Meningococcal vaccine appears to be immunogenic in such individuals. PMID- 8442923 TI - Chemotherapy of African AIDS diarrhoea: a preliminary study. AB - OBJECTIVE: To determine whether combined chemotherapy with tinidazole, thiabendazole and cotrimoxazole is more effective than placebo in treatment of AIDS diarrhoea in Zambia. DESIGN: Single-blind prospective comparison in consecutive patients, randomized alternately to placebo or chemotherapy. SETTING: A district hospital in Zambia. PATIENTS: Sixty-four HIV-seropositive patients with chronic diarrhoea were considered for inclusion in the study. Of these, 25 patients were not eligible for randomization (in 13 cases because of spontaneous remission); 11 were randomized, but excluded from the analysis (seven failed to attend for a scheduled visit and four died), leaving 28 patients who completed the study. MAIN OUTCOME MEASURES: Proportion of diarrhoea-free days in the 7 days following treatment, as determined by daily stool counts. RESULTS: There were 38 diarrhoea-free days out of 89 (43%) in the placebo group, and 39 out of 72 (54%) in the chemotherapy group; this difference was not statistically significant. CONCLUSIONS: The high level of spontaneous remission probably indicates a natural fluctuation in stool frequency and demonstrates the need for placebo-controlled studies in any assessment of therapy for AIDS diarrhoea. Our findings do not allow us to conclude that the chemotherapy used is ineffective, since the number of patients was low, but will help in our understanding of the natural history of the disorder and the design of future studies. PMID- 8442924 TI - Non-ulcerative sexually transmitted diseases as risk factors for HIV-1 transmission in women: results from a cohort study. AB - OBJECTIVES: The heterosexual spread of HIV-1 is occurring at different rates in different parts of the world. The transmission probability of HIV-1 per sexual contact is low, but may be greatly enhanced by several cofactors. Sexually transmitted diseases (STD), especially genital ulcers, may be such factors. So far, epidemiological evidence that other STD facilitate HIV-1 transmission is weak. The objective of this study was to determine whether treatable STD enhanced sexual transmission of HIV-1 in a cohort of female prostitutes in Kinshasa, Zaire. METHODS: We conducted a nested case-control study of 431 initially HIV-1 negative women followed prospectively for a mean duration of 2 years (with monthly STD check-ups and 3-monthly HIV-1 serology). Cases (seroconverters, n = 68) were compared with controls (women who remained HIV-1-negative, n = 126) for incidence of STD and sexual exposure during the presumed period of HIV-1 acquisition. RESULTS: The annual incidence of HIV-1 in this cohort was 9.8%. Seroconverters were younger than HIV-1-negative women (mean age, 24.6 versus 26.8 years; P = 0.04). During the period of HIV-1 acquisition, cases had a much higher incidence of gonorrhoea, chlamydial infection and trichomoniasis, and engaged in unprotected sex with clients and partners more frequently than controls. After controlling for sexual exposure by multivariate analysis, adjusted odds ratios for seroconversion were 4.8 [95% confidence interval (CI), 2.4-9.8] for gonorrhoea, 3.6 (95% CI, 1.4-9.1) for chlamydial infection and 1.9 (95% CI, 0.9 4.1) for trichomoniasis. Genital ulcers were more frequent in cases than controls, but much less common than other STD. CONCLUSION: Non-ulcerative STD were risk factors for sexual transmission of HIV-1 in women, after controlling for sexual exposure. Because of their high prevalence in some populations, non ulcerative STD may represent a considerable population-attributable risk in the transmission of HIV-1 worldwide. The identification of treatable STD as risk factors for HIV-1 transmission offers an important additional strategy for the prevention of HIV/AIDS. PMID- 8442925 TI - Molecular structures of L-Leu-L-Tyr, Gly-D,L-Met.p-toluenesulfonate and L-His-L Leu. AB - L-Leu-L-Tyr, (I), C15H22N2O4, M(r) = 294.35, crystallizes from MeOH/5% dimethyl sulfoxide in the orthorhombic space group P2(1)2(1)2(1). a = 5.644 (1), b = 12.094 (3), c = 22.548 (4) A, V = 1539.0 (5) A3, Z = 4, Dx = 1.270 g cm-3, Cu K alpha, lambda = 1.54184 A, mu = 7.228 cm-1, F(000) = 632, T = 173 K, final R (on F) = 0.033 for 1347 observations with I > or = 2 sigma (I). (I) crystallizes as a zwitterion with the N-terminus protonated and the C-terminus ionized. The peptide backbone adopts a distorted trans antiparallel beta pleated-sheet conformation, with principal torsion angles psi 1 = 163.7 (2), omega 1 = 158.7 (2), phi 2 = 110.9 (3) and psi 2 = 141.4 (2)degrees. The leucyl residue is in the g-(tg-) conformation while the tyrosyl residue adopts the g- conformation, with the phenol ring twisted from the low-energy perpendicular position. Gly-D,L-Met.p toluenesulfonate, (II), C7H15N2O3S+.C7H7O3S-, M(r) = 378.47, crystallizes from MeOH/EtOAc in the orthorhombic space group Pbca. a = 33.642 (4), b = 15.951 (1), c = 6.785 (1) A, V = 3641.0 (4) A3, Z = 8, Dx = 1.381 g cm-3, Cu K alpha, lambda = 1.54184 A, mu = 28.865 cm-1, F(000) = 1600, T = 223 K, final R (on F) = 0.055 for 1669 observations with I > or = 3 sigma (I). Gly-D,L-Met exists as a cation with the N- and C-termini protonated, the p-toluenesulfonate being the counterion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8442926 TI - Space-group determination of human tooth-enamel crystals. AB - In the present work, we have determined the space group of human tooth-enamel crystals using--for the first time for a biological crystal--convergent beam electron diffraction (CBED). The symmetries observed in the different patterns we have obtained lead us to the P6(3)/m hydroxyapatite space group. Disorder, most likely situated in the columns formed by the hydroxyl ions of the crystals, is suggested as a cause of weak intensity in the otherwise forbidden 000l (l odd) reflections and low visibility of first-order Laue zone (FOLZ) reflections in the CBED pattern from crystals oriented along the [0001] zone axis. A monoclinic phase was not observed. PMID- 8442927 TI - Structural studies on DNA-binding drugs: crystal structure and molecular dynamics studies of triazoloacridinones. AB - Structural and conformational studies on two 8-substituted triazoloacridinone antitumor agents, C1295 and C1303, have been carried out to compare the conformation of the (aminoalkyl)amino side chain and the effect of C-8 substitution. Crystal data for 5-[2-(diethylamino)ethylamino]-8-methyl-6H-[1,2,3] triazolo[4,5,1- de]acridin-6-one (C1295), C20H23N5O, M(r) = 349.4, triclinic, P1, a = 12.200 (1), b = 14.890 (1), c = 5.185 (1) A, alpha = 93.54 (1), beta = 102.21 (1), gamma = 80.61 (1)degree, V = 907.9 (1) A3, Z = 2, Dx = 1.278 g cm-3, lambda(Cu K alpha) = 1.54178 A, mu = 6.2 cm-1, F(000) = 372, T = 293 K, R = 0.061 for 1631 observed reflections; for 5-[2-(diethylamino)ethylamino]-8- hydroxy-6H [1,2,3]triazolo[4,5,1-de]acridin-6-one (C1303), C17H17N5O2, M(r) = 323.4, monoclinic, P2(1)/n, a = 15.823 (2), b = 5.790 (1), c = 16.856 (2) A, beta = 98.59 (1)degree, V = 1526.9 (2) A3, Z = 4, Dx = 1.404 g cm-3, lambda(Cu K alpha) = 1.54178 A, mu = 7.5 cm-1, F(000) = 680, T = 293 K, R = 0.054 for 1303 observed reflections. There is a difference in the orientation of the (aminoalkyl)amino side chain in the two compounds in the solid state, but molecular dynamics simulations indicate that in the gas phase the orientation is very similar. This difference could result from the different crystal packing in the case of C1303, due to the presence of an intermolecular hydrogen bond.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8442928 TI - Internal vibrations of a molecule consisting of rigid segments. I. Non interacting internal vibrations. AB - For molecular crystals, a procedure is proposed for interpreting experimentally determined atomic mean square anisotropic displacement parameters (ADPs) in terms of the overall molecular vibration together with internal vibrations with the assumption that the molecule consists of a set of linked rigid segments. The internal librations (molecular torsional or bending modes) are described using the variable internal coordinates of the segmented body. In paper I of this two part report, it is assumed as a zero-order approximation that the internal vibrations about the linkage axes between pairs of segments are uncorrelated with each other and with the overall molecular rigid-body vibrations. As a first-order approximation, the possibility that each internal vibration can be correlated with the external vibrations is also considered. An important feature of this approach is that the internal librations are required to give zero contribution to the overall momentum of the molecule at all times, so the internal coordinates must be orthogonal to the external ones. Also, each of the internal librations involves the motion of all atoms in the molecule. The resulting internal vibrational parameters are invariant to the choice of reference segment. With this procedure, the experimental ADPs obtained from crystal structure determinations involving six small molecules (sym-trinitrobenzene, adenosine, tetra-cyanoquinodimethane, benzamide, alpha-cyanoacetic acid hydrazide and N acetyl-L-tryptophan methylamide) have been analyzed. As a consequence, vibrational corrections to the bond lengths and angles of the molecule are calculated as well as the frequencies and force constants (with e.s.d.'s) for each internal torsional or bending vibration. Compared with other models used for describing internal vibrations, there are differences in how the total ADP is partitioned between the internal and overall molecular vibrations. PMID- 8442929 TI - The asymmetric regions of rotation functions between Patterson functions of arbitrarily high symmetry. AB - Rotation functions between Patterson functions can be calculated and analyzed more efficiently when it is possible to consider only a unique or asymmetric region of rotation space. Previous authors have succeeded in characterizing the symmetries and asymmetric units of rotation functions between Patterson functions whose symmetries are less than cubic. Here we describe a simple and general solution that applies to rotation functions between Patterson functions of any symmetry, including cubic. The method relies on partitioning rotation space into Dirichlet domains. PMID- 8442930 TI - The severity of visual hemineglect follows a bimodal frequency distribution. AB - The purpose of this study was to determine whether the severity of visual hemineglect follows a unimodal or bimodal frequency distribution. Seventy-seven consecutive patients with a unilateral cerebral infarct (36 left- and 41 right hemisphere lesions) were evaluated. The severity of neglect was measured as the number of omissions on a line cancellation task. The frequency distribution of the number of lines omitted was bimodal following right lesions. One group of patients showed no or only mild neglect, whereas other patients showed severe neglect. Very few patients showed neglect of intermediate severity. The frequency distribution following left lesions was unimodal. Most patients exhibited no or only mild neglect. These results suggest that, following right lesions, the dichotomy regarding the severity of neglect is real and cannot be explained by observers' tendency to categorize. PMID- 8442931 TI - Nonverbal amnesia and asymmetric cerebral lesions following encephalitis. AB - Global amnesia after herpes simplex encephalitis has been typically associated with lesions of anterior and medial temporal lobe, inferior and medial frontal lobe, and insula. The neuropathologic correlates of this disease are usually considered to be bilateral and similar across cases. We describe a 27-year-old woman whose chronic amnesia and cerebral lesions after viral encephalitis indicate a different pattern. Two features distinguish her presentation: (1) markedly asymmetric lesions extensively involving the right temporal lobe but sparing almost all of the same structures on the left and (2) severe compromise of nonverbal learning and a nonverbal retrograde amnesia in contrast to disproportionately small impairments of verbal learning and retention. The findings suggest that encephalitis patients cannot be treated as a homogeneous group and that detailed analysis of variability in their anatomic lesions may be an important explanatory factor in neural accounts of these severe human amnesias. PMID- 8442932 TI - On the interdependency between attentional biases and visual field effects with bilateral presentations of stimuli. AB - Previous research indicates that bilateral presentations of visual stimuli yield greater visual field differences than unilateral ones. Although this fact has generally been interpreted by reference to functional models of hemispheric specialization, an alternative explanation has been offered, which suggests that it is artifactually caused by an attentional bias (AB). Indeed, consistent positive correlations between the direction of ABs and that of visual field effects have been reported. However, this relationship remains uncertain since different tasks, presented at different moments, have been used in order to document it. We report on a bilateral presentation task which controlled this potential discrepancy by mixing trials measuring ABs with those assessing visual field effects. We showed that, in a group of dextrals, the direction of the visual field effect is intimately correlated with that of the AB; subjects with a right AB showed a right visual field advantage, whereas subjects with a left AB showed a left visual field advantage; moreover, subjects with no overall AB did not show any visual field advantage. The results of this experiment confirm the fact that the formally reported correlations between the direction of ABs and visual field effects are determined by individual differences in ABs rather than by the task being used to assess them. This observation points to the necessity for further research on variables affecting the between-subjects variability in ABs with the use of bilateral presentations of visual stimuli. PMID- 8442933 TI - Implicit memory and the formation of new associations in nondemented Parkinson's disease individuals and individuals with senile dementia of the Alzheimer type: a serial reaction time (SRT) investigation. AB - Using the serial reaction time (SRT) task developed by Nissen and Bullemer (1987, Cognitive Psychology, 19, 1-32), implicit memory performance was examined in four groups of subjects: nondemented healthy aged individuals; nondemented Parkinson's disease individuals; very mildly demented senile dementia of the Alzheimer type (SDAT) individuals; and mildly demented SDAT individuals. The SRT task involved four blocks of a repeated 10-item keypress sequence that tapped general skill development along with a fifth block of a nonrepeated sequence that presumably reflected the impact of switching from a learned set of associations (developed during the first four blocks) to a novel sequence. The increase in response latency from the fourth repeated block to the fifth nonrepeated block was used as the reflection of implicit learning. The results revealed preserved implicit memory performance in the very mildly demented individuals compared to that of the age-matched control individuals. However, the mildly demented SDAT individuals and the nondemented Parkinson's disease individuals showed reliably less implicit learning, compared to the age-matched control individuals. Differences between the past studies using the SRT task to tap implicit memory performance in SDAT individuals and the present study are discussed in some detail. We conclude that nondemented Parkinson's disease individuals and mildly demented SDAT individuals produce some deficit in the formation of new associations in implicit memory, as measured by the SRT task. PMID- 8442934 TI - Visual field effects of classical migraine. AB - Although classical migraine is known to produce lateralized sensory disturbances (e.g., visual "fortification" structures), its effect on higher order processes is unknown. Here four lateralized visual tasks were repeatedly presented to a single subject (the author) over a 2 1/2-year span, during both classical migraine attacks and headache-free periods. Attacks varied as to inferred hemispheric locus. All four tasks ("words," "typing," "bar graphs," and "locations") produced significant or marginally significant visual field (VF) by condition interactions, results generally consistent with a phasic impairment of function in the migrainous hemisphere. A content analysis of notes made during the attacks suggests that among other symptoms, alphabetic indistinctiveness and spatial disturbances are characteristics of left and right hemisphere attacks, respectively. Aspects of the results argue against any major influence of demand characteristics. PMID- 8442935 TI - Skill and hemispheric specialization in detecting featural differences in visual images. AB - Visual asymmetry patterns related to skill were examined during a target-probe matching task in 24 skilled medical technologists and 24 matched controls. On each of 240 test trials, digitized replicas of specimens commonly encountered in medical laboratory diagnostics were shown centrally for 500 msec. Each target was immediately followed by a lateralized probe item for 120 msec that was either an exact copy (positive probe) or a distorted version (negative probe) of the target. Difficulty level of target-probe matching was manipulated on negative probe trials; half of the negative items consisted of difficult discriminations which were selected to assess the effects of domain-specific experience on detecting small differences in salient morphological features. Medical technologists exhibited a right visual field advantage, but were not different from the control subjects in speed or accuracy to positive probes or to easy negative probes. The observed left-hemisphere advantage in skilled visual processing is attributed to the beneficial effects of experience on the development of domain-specific visual analysis skills. PMID- 8442936 TI - Target detection deficits in frontal lobectomy. AB - We examined the hypothesis of dorsomedial frontal lobe involvement in target detection through the effects of distractor interference and multiple target interference on unilateral lobectomy patients. Seven patients who underwent a unilateral frontal lobectomy for epilepsy involving dorsomedial cortex and variable amounts of lateral cortex were compared to 10 patients with a unilateral temporal lobectomy and to 10 normal adults on a visual character cancellation task. The task involved detecting occurrences of target characters embedded in rows of characters under three conditions: detection of one target character in the absence of distractors, detection of one target character among distractors, and detection of three targets among distractors. Visual detection performance was compared to that in the Stroop reading interference task. Frontals were predictably slower than the other groups in the baseline conditions of the character cancellation task and the Stroop task. After partialing out baseline detection performance in the character cancellation task, frontals showed an almost normal detection in the presence of distractors but were distinctly slower and made more errors than the other groups in multiple target detection. Frontals were also slower on the Stroop even after partialing out baseline naming performance. Temporals were normal on all tasks. Results suggest that frontal damage can affect selectivity in target detection as well as the Stroop and that this deficit is independent of the general psychomotor slowing observed in these patients. PMID- 8442937 TI - Haptic discrimination of nonsense shapes: hand exploratory strategies but not accuracy reveal laterality effects. AB - Studies on haptic processing show inconsistent results concerning sex and hand differences. We present a novel approach in which manual exploratory strategies were examined. Twenty-four right-handed adults of both sexes had to monohaptically explore unseen meaningless stimuli and then to recognize their visually presented outline drawings among drawings of different stimuli. Tactual stimuli were composed of eight smoothly joined cubes whose junctions were not haptically discernible. The computer recorded number and duration of hand contacts on each cube. Analyses included the accuracy of the recognition phase, the number and duration of exhaustive explorations of the stimulus, and the number of cubes simultaneously touched. Neither hand nor sex differences were found for the accuracy measurement. The number and duration of exhaustive explorations also provide no evidence of hand differences. However, the left hand touched simultaneously more cubes than the right and this asymmetry was more pronounced in males than in females. Such an asymmetry was apparent in the very first contact of the hand with the shape. It is suggested that exploratory strategies may be more sensitive measures in revealing hand lateralization than the accuracy measurement. PMID- 8442938 TI - Neural mechanisms of tinnitus. AB - The theoretical concepts underlying the neural origin of tinnitus are outlined. Several neurophysiological models are reviewed critically and the impact of the pathological ensemble spontaneous activity of the auditory system for the diagnosis and therapy of tinnitus is described in more detail. PMID- 8442939 TI - Interaction of human mast cell tryptase and chymase with low-molecular-mass serine proteinase inhibitors from the human respiratory tract. AB - Mast cell degranulation results in the release of serine class proteinases with trypsin- and chymotrypsin-like specificity. While looking for natural protein inhibitors of these enzymes, we studied their reactions with the double-headed Kunitz-type inhibitor, bikunin, and the human bronchial secretion inhibitor (BSI), which are the only known low-molecular-mass proteinase inhibitors of the human respiratory tract. Both trypsin and chymotrypsin can be inhibited by these inhibitors. However, human BSI is unable to inhibit human tryptase and is the physiological counterpart of chymase in the upper respiratory tract. Human bikunin is unable to inhibit human chymase and human tryptase. Furthermore, human tryptase is also not inhibited by a fragment that consists only of the trypsin specific C-terminal inhibitor domain of human bikunin. This finding contradicts reports that claim the occurrence of a tryptase-specific proteinase inhibitor in rat mast cells. PMID- 8442940 TI - Blood flow through irradiated rabbit submandibular glands measured with fluorescein angiography. AB - Microvascular injury has been regarded as a contributing factor in irradiation damage of biologic tissues, including morphologic changes and increased permeability of the vascular network. The late irradiation effect on the capillary circulation of salivary glands was studied with dynamic fluorescein angiography. In 31 rabbits one side of the head was exposed to a single radiation dose of 15 Gy. At 4 and 10 months thereafter no significant difference was detectable in the microcirculation between the unshielded and shielded glands. PMID- 8442941 TI - Protein tyrosine kinase activity in laryngeal squamous cell carcinoma. AB - Oncogenes play an important role in the process of malignant transformation. Since many of the protein tyrosine kinases (PTK) are products of oncogenes, the aim of this study was to demonstrate whether an increased PTK activity could be found in head and neck tumors. By using a non-radioactive dot-blot assay, PTK activity was measured in tumor and normal tissues of 38 patients with laryngeal cancer. The control group consisted of 19 healthy persons. PTK activity in tumor cells was significantly higher (P < 0.001) than in normal cells of the tumor patients and normal controls. Additionally, the PTK activity in the normal mucosa of the tumor patients was significantly higher than in the normal mucosa of the control group. PMID- 8442942 TI - Phenol anesthesia of the tympanic membrane in purulent otitis media: a structural analysis in the rat. AB - In the present study, local anesthetics were applied to the tympanic membrane (TM) of rats following experimentally evoked purulent otitis media (POM). The structure of the TM was evaluated 24 h, 2 weeks and 3 months after application of phenol to a discrete are of the right TM. The left ear was used as a control. POM induced swelling of all tissue layers of the pears tensa. The tissues were invaded by inflammatory cells and disintegrated. The fibrous layer also dissolved, leaving spontaneous perforations. However, phenol on inflamed TMs did not further alter the TM structure. These findings infer that the injurious effect of topical anesthesia on the intact TM is more or less negligible when applied to diseased TMs. PMID- 8442943 TI - Convergence of olfactory and nasotrigeminal inputs and possible trigeminal contributions to olfactory responses in the rat thalamus. AB - To elucidate the role of trigeminal input on the olfactory system, field-evoked potentials were measured following electrical stimulation of the nasociliary branch of the trigeminal nerve in the olfactory-related structures in the rat brain. Significant potential changes were recorded in the mediodorsal nucleus of the thalamus and the lateral hypothalamic area. In the mediodorsal nucleus of the thalamus, the neurons responding to olfactory bulb electrical stimulation also responded to trigeminal nerve stimulation. Single neuronal responses of mediodorsal thalamic neurons following odorant stimulation were enhanced by blockade of the trigeminal nerve with procaine. These results suggest that olfactory and trigeminal pathways converge on the same neural elements within the mediodorsal nucleus of the thalamus and that the trigeminal input may modulate olfactory input in this nucleus. PMID- 8442944 TI - Prognostic significance of epidermal growth factor receptor in squamous cell carcinoma of the maxillary sinus. AB - The expression of epidermal growth factor receptor (EGFR) was determined immunohistochemically in two groups of maxillary sinus squamous cell carcinomas, one with recurrences at the primary site after combination therapy with radiotherapy, chemotherapy and/or surgery and one without local recurrences. Using a four-graded scale (-, +, + +, + + +), 9 of the 10 recurrent carcinomas had a staining intensity and proportion of stained cells of + + or more. A comparable staining intensity was found in 9 of the 18 non-recurrent carcinomas. This difference is statistically significant (Fisher's exact probability test, P < 0.05). These results indicate that an increased expression of EGFR may influence the recurrence rate of squamous cell carcinoma of the maxillary sinus after combined therapy. PMID- 8442945 TI - The use of auto-correlation function to quantify periodicity in smooth pursuit. AB - Smooth pursuit eye movement was recorded with a DC amplifier during horizontal sinusoidal target movement at 0.3, 0.6, 0.8, 1.0 and 1.2 Hz. Eye movement was digitalized at 100 Hz and 12 bits accuracy. The digitalized eye movements were analyzed by the auto-correlation function, and the auto-correlation coefficient was used to quantify periodicity. In 13 healthy volunteers, the auto-correlation coefficient was nearly equal to 1.0 at 0.3 Hz but gradually decreased as the target frequency increased. In 8 patients with various neurological disorders, the auto-correlation coefficient was significantly smaller at all target frequencies than in the healthy volunteers. Less periodicity, as indicated by the decreased auto-correlation coefficient, suggests a disorder in the control visual feedback mechanism in smooth pursuit. PMID- 8442946 TI - Distribution of the afferent neurons from the canine recurrent laryngeal nerve. AB - Localization of the afferent neurons from the canine recurrent laryngeal nerve in the nodose ganglia (NG) and jugular ganglia was studied using the horseradish peroxidase technique. Labeled cells were detected in the ipsilateral NG and presented no distinct pattern of distribution, but rather were scattered throughout the ganglion. No labeled cells were found in the contralateral NG or bilateral jugular ganglia. The size of labeled cells varied from 15 microns to 60 microns. Two to six labeled cells larger than 45 microns were detected in each dog. Most of the labeled cells (62%) had a diameter between 30 microns and 45 microns. The percentage of labeled cells with a diameter between 15 microns and 30 microns was 30% and between 45 microns and 60 microns was 8%. This difference in size of labeled cells in the NG may be related to functional differences among the receptors mediated. PMID- 8442947 TI - Anti-Borrelia burgdorferi antibodies in patients with facial paralysis. AB - Ninety-eight patients with facial paralysis were studied by an indirect enzyme linked immunosorbent assay (ELISA) employing two types of Borrelia burgdorferi antigen, namely sonic extract and flagellum protein of B. burgdorferi. IgG or IgM antibodies were detected by sonic extract ELISA in 22 (32.4%) of 68 patients with Bell's palsy, and in 2 (10.0%) of 20 patients with varicella-zoster virus infection. This difference was statistically significant (P < 0.05). A positive reaction was more frequent with the sonic extract antigen, while the positive rates were significantly increased in Bell's palsy patients with hyperglobulinemia (P < 0.05). IgM antibodies were also significantly more frequently observed in patients who developed Bell's palsy between October and March (P < 0.05). Since none of the patients had a history suggestive of Lyme disease, some kind of non-specific reaction and certain undefined factors linked to a positive reaction against B. burgdorferi could be involved in Bell's palsy. PMID- 8442948 TI - An anatomical, morphological and electrophysiological study of the rabbit facial nerve in the temporal bone. AB - Anatomical, histological and electrophysiological features of the rabbit facial nerve in the temporal bone are described for research purposes. Based upon the findings the rabbit intratemporal facial nerve is surgically accessible and consists of a constant axon number and myelin sheath thickness. As a valid model the rabbit intratemporal nerve can be readily utilized for research studies in nerve regeneration pertinent to the facial nerve in this region. PMID- 8442949 TI - Evaluation of contralateral acoustic brain stem reaction in patients with pontocerebellar angle tumors. AB - Contralateral acoustic brain stem response (ABR) waveforms were analyzed in 63 subjects with tumors of the pontocerebellar angle. The tumors were diagnosed by CT and the diagnoses were surgically confirmed. According to the latency changes and amplitude sizes, the ABR waveforms were classified into four types (O, A, B and C). All tumors were separated into groups (depending on size), and into subgroups (depending on type). Contralateral ABR was found to be affected by tumors greater than 20 mm, and significantly more often by neuroma than by other tumors (significance level 5%). PMID- 8442950 TI - Cytoplasmic beta-actin promoter produces germ cell and preimplantation embryonic transgene expression. AB - The cytoplasmic beta-actin promoter, commonly used as strong promoter in many gene regulation studies, produces a pattern of male germ cell and preimplantation, embryonic gene expression in transgenic mice. In seven of ten expressing transgenic lines, a chicken beta-actin-lacZ fusion gene was expressed in adult testes. In addition, five of the ten lines demonstrated transgene expression in the preimplantation mouse embryo. This is the first example of transgene expression at the stages of both gamete and early embryo. Overall, the site or transgene integration appeared to influence transgene expression in adult tissues. PMID- 8442951 TI - Quantitative estimation of chimerism in mice using microsatellite markers. AB - An embryonic stem cell line was established from SV129 mouse blastocysts and used to generate chimeric mice by injection into OF1 blastocysts; 18 out of the 30 resulting offspring appeared chimeric as judged from their coat color patterns, and 3 of the 13 males proved to be germ-line chimeras as they transmitted the SV129 agouti phenotype to all or part of their offspring. The degree of chimerism of these males was evaluated for different tissues using polymorphic microsatellite markers amplified by the polymerase chain reaction. It was shown that these new markers can be effectively used to quantitatively estimate levels of chimerism. The CKMM (creatine kinase, muscle) microsatellite system was used to distinguish the SV129 from the OF1 genotype. In all performed tests, the correlation between DNA ratio and signal ratio, expressed as a base 10 logarithm, was shown to exceed or equal 0.98 for known DNA ratios (SV129/OF1) ranging from 1/99 to 99/1. Linear calibration methods were used to predict the % SV129 DNA of a test sample based on the obtained signal ratio. The accuracy of the prediction was evaluated by performing repeated measurements. Differences among three repeated estimates ranged from 2 to 17% for a given sample. Microsatellite systems should be very useful to monitor chimerism involving strains that can not be discerned with coat color or biochemical markers. This will be particularly important when ES methodology becomes available in species other than mice. PMID- 8442952 TI - Evidence for nuclear internalization of exogenous DNA into mammalian sperm cells. AB - Mature sperm cells have the spontaneous capacity to take up exogenous DNA. Such DNA specifically interacts with the subacrosomal segment of the sperm head corresponding to the nuclear area. Part of the sperm-bound foreign DNA is further internalized into nuclei. Using end-labelled plasmid DNA we have found that 15 22% of the total sperm bound DNA is associated with nuclei as determined on isolated nuclei. On the basis of autoradiographic analysis, nuclear permeability to exogenous DNA seems to be a wide phenomenon involving the majority of the sperm nuclei. In fact, the foreign DNA, incubated with sperm cells for different lengths of time, is found in 45% (10 min) to 65% (2 hr) of the sperm nuclei. Ultrastructural autoradiography on thin sections of mammalian spermatozoa, preincubated with end-labelled plasmid DNA, shows that the exogenous DNA is internalized into the nucleus. This conclusion is further supported by ultrastructural autoradiographic analysis on thin sections of nuclei isolated from spermatozoa preincubated with end-labelled DNA. PMID- 8442953 TI - Cloning and sequencing of baboon and cynomolgus monkey intra-acrosomal protein SP 10: homology with human SP-10 and a mouse sperm antigen (MSA-63). AB - In this study, cDNAs encoding the intraacrosomal protein SP-10 were cloned and sequenced from baboon (Papio papio) and macaque (Macaca fascicularis) testis libraries and the sequence compared to that of human SP-10. Two alternatively spliced SP-10 cDNAs were obtained from both baboon and macaque testis libraries. The two cDNAs in each species contained open reading frames encoding proteins of exactly 285 and 251 amino acids. A 98% homology between baboon and macaque SP-10 was found at the protein and DNA levels. An 85% and 89% homology between baboon and macaque SP-10 and human SP-10 was present at the protein and DNA level, respectively. A mouse intraacrosomal protein, MSA-63, considered to be an SP-10 homologue, exhibited an overall 53% homology to nonhuman primate SP-10 and a 60% homology to human SP-10 at the protein level. Polymerase chain reaction analysis of testis mRNA confirmed the existence of two alternatively spliced SP-10 mRNAs in both nonhuman primates. Primer extension analysis indicated a common major transcriptional start site in baboon, macaque, and human SP-10 67 nucleotides 5' to the ATG codon. The amino acid sequence data for nonhuman primate SP-10s suggest that antibodies generated by vaccinating baboons and macaques with human SP-10 will likely recognize nonhuman primate SP-10, supporting the testing of an SP-10 contraceptive vaccine based on human SP-10 in these nonhuman primate models. PMID- 8442954 TI - Lipid globules at the midpieces of Glyptocidaris crenularis spermatozoa and their relation to energy metabolism. AB - Spermatozoa of the sea urchin, Glyptocidaris crenularis, use endogenous triglycerides (TG), not phosphatidylcholine, to produce energy for swimming. This study was undertaken to examine ultrastructurally the location of TG available for utilization in energy metabolism in these spermatozoa. Each spermatozoon contained several lipid globules at the bottom of the midpiece. Following incubation with sea water, both the number and size of the lipid globules decreased significantly. The total volume of lipid globules in each spermatozoon was roughly halved after 1 h of incubation. Similarly, about half of the TG was metabolized during the same incubation period. Oxygen consumption by spermatozoa during the incubation indicated the oxidation of fatty acid derived from TG. Thus it appears that G. crenularis spermatozoa obtain energy through oxidation of fatty acid from TG stored in the lipid globules within their midpieces. PMID- 8442955 TI - Differential sensitivity of progesterone- and zona pellucida-induced acrosome reactions to pertussis toxin. AB - Pertussis toxin-sensitive guanine nucleotide-binding regulatory proteins (G proteins) have previously been shown to mediate the zone pellucida-induced acrosome reaction in mammalian sperm. In this study we compared the inhibitory effect of pertussis toxin on the zona-induced acrosome reaction in human spermatozoa with that on the reaction induced by progesterone, another physiological acrosome reaction-promoting stimulus associated with the ovulated oocyte. Up to the concentration of 1 microgram/ml, pertussis toxin did not produce any direct effects on the acrosome reaction frequency nor did it influence sperm movement and viability. However, preincubation of spermatozoa with the toxin at a concentration of 100 ng/ml completely abolished the increase in the acrosome reaction frequency upon subsequent exposure to solubilized zona pellucida material. In contrast, the same treatment did not impair the ability of spermatozoa to initiate the acrosome reaction in response to progesterone. Moreover, the preincubation with pertussis toxin did not modify the changes in the intracellular concentration of calcium ions occurring after progesterone addition. These data suggest that different physiological stimuli may utilize different signal transduction pathways to induce the human sperm acrosome reaction. PMID- 8442956 TI - The effect of warming velocity on motility and acrosomal integrity of boar sperm as influenced by the rate of freezing and glycerol level. AB - The effect of thawing velocities ranging from 10 degrees C/min to 1,800 degrees C/min on the motility and acrosomal integrity of boar spermatozoa frozen at 1 degree C/min (suboptimal), 5 degrees C/min, and 30 degrees C/min (optimal) rate was studied with the sperm suspended for freezing in diluent containing 2, 4, or 6% of glycerol (v/v). The influence of thawing on sperm survival depends on the rate at which the sperm had been frozen. In semen frozen at a suboptimal rate of 1 degree C/min, the percentage of motile sperm (FMP) initially fell to 3.5-4.0% when the thawing rose to 200 degrees C/min, but, with further increases in thawing rate, increased and reached peak values (10.3-11.0% FMP) after thawing at 1,800 degrees C/min. The percentage of sperm with normal apical ridge (NAR) also increased moderately with thawing rate, but the degree of improvement decreased as the glycerol level was increased. In semen frozen at 1 degree C/min, acrosomal integrity (NAR) was best maintained in 2% glycerol, reaching 22.9% NAR after thawing at 1,800 degrees C/min. In semen frozen at the optimal rate of 30 degrees C/min, the increases in thawing rates above 200 degrees C/min substantially improved motility. Motility was generally higher in semen protected by 4 or 6% glycerol, with the peak values of 44 or 46% FMP, respectively, after thawing at 1,200 degrees C/min. The proportion of sperm with NAR also increased with thawing rate, but as in the case of suboptimally frozen sperm it was influenced negatively by the glycerol concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8442957 TI - Fine structure of the spermatozoa of Crassostrea gigas (Mollusca, Bivalvia). AB - We describe sperm ultrastructure and acrosome differentiation during spermiogenesis in Crassostrea gigas (Mollusca Bivalvia). The sperm cell is a uniflagellated cell of the primitive type. The head region contains a rounded or conical nucleus surmounted by small acrosome. This organelle consists of a membrane-bound acrosomal granule, the contents of which have a homogeneous density, except in the anterior region, which is positive for PTA. The acrosome also surrounds the perforatorium, which includes oriented fibrillar elements: this is the axial body. The middle piece contains four mitochondria encircling two perpendicular centrioles. The distal centriole is provided with a system of mechanical fixation to the plasma membrane, consisting of nine fibers in radial arrangement. The tail flagellum, about 50 microns long, contains the usual microtubular axoneme. PMID- 8442958 TI - Electrically induced calcium elevation, activation, and parthenogenetic development of bovine oocytes. AB - The influence of electrical stimulation on the level of intracellular Ca2+ in bovine oocytes, as well as activation and extent of parthenogenetic development, was investigated. Mature oocytes were electrically stimulated at 29 hr of maturation, and intracellular Ca2+ concentration was determined with the Ca2+ indicator fura-2 dextran (fura-2 D). The Ca2+ response of oocytes to a given electrical pulse was variable. Oocytes responded with either no Ca2+ rise from baseline (approximately 12 nM), a short-duration Ca2+ rise (from 12 nM to 300 nM) that returned to baseline within 2 min of the pulse, or a long-duration Ca2+ rise (from 12 nM to 1,000-2,000 nM) that never returned to baseline during the 8 min period over which the oocytes were monitored. In these oocytes, Ca2+ level returned to baseline when oocytes were removed from 0.30 M mannitol and placed in an ionic medium. Increasing field strength or pulse duration tended to increase the proportion of oocytes displaying a Ca2+ rise, and at 1.0 kVcm-1 for 40 microseconds, all oocytes displayed a long-duration Ca2+ elevation. Direct transfer of oocytes from culture medium to mannitol also triggered a Ca2+ rise. Multiple stimulations, either electrical or by transferring to mannitol, produced multiple Ca2+ rises. This mannitol-induced Ca2+ rise could be inhibited by first washing the oocytes in medium containing equal parts of 0.30 M mannitol and phosphate buffered saline (PBS). The level of Ca2+ stimulation affected activation and development of oocytes. Insufficient, or, conversely, excessive Ca2+ stimulation impaired development. Optimum development was obtained with 1) three pulses of 0.2 kVcm-1 for 20 microseconds, each pulse 22 min apart, after direct transfer of oocytes from culture medium to mannitol (22% blastocysts) or 2) three pulses of 1.0 kVcm-1 for 20 microseconds after transfer of oocytes from culture medium to medium containing equal parts mannitol and PBS, then to mannitol (24% blastocysts). This procedure avoided induction of a Ca2+ rise prior to the pulse. The results indicate that the level of Ca2+ stimulation can be regulated by incubation conditions prior to the pulse and, to some extent, by field strength and pulse duration. The level of electrical stimulation influenced oocyte Ca2+ response, activation, and parthenogenetic development. PMID- 8442959 TI - Histone H1 kinase activity in bovine oocytes following calcium stimulation. AB - The influence of number of Ca2+ stimulations on the profile of histone H1 kinase activity in bovine oocytes was investigated. A CA2+ stimulation consisted of transferring oocytes directly from culture medium to mannitol containing 100 microM Ca2+ and pulsing oocytes with a 0.2 kVcm-1, 20 microseconds discharge. One, three, or six Ca2+ stimulations were given, each 22 min apart. Oocytes were frozen from 0 to 8 hr after the first stimulation at indicated time points and assayed for histone H1 kinase activity. H1 kinase activity was quantified using a densitometer and expressed as a percent of activity in nonpulsed metaphase II oocytes. Stimulating oocytes in the absence of Ca2+ in the pulsing medium did not inactivate H1 kinase. In the presence of Ca2+, however, H1 kinase was rapidly inactivated after stimulation. A single stimulation decreased H1 kinase activity to 44% +/- 11% of its initial level in 1 hr. However, H1 kinase was dramatically reactivated at 2 hr after the stimulation and reached 122% +/- 22% of the initial activity at 6 hr. With three stimulations, basal H1 kinase activity was 21% +/- 3% and was obtained in 30 min. H1 kinase reactivation started at 4 hr after the first stimulation and level of activity reached 38% +/- 15% at 8 hr. Six stimulations also led to rapid H1 kinase inactivation and to a basal activity of 14% +/- 0.4%. With six stimulations, however, basal H1 kinase activity was maintained over at least 8 hr, and no reactivation occurred during this period. Basal H1 kinase activity obtained after six stimulations was similar to that of fertilized oocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8442960 TI - The open globe: is an alternative to succinylcholine necessary? PMID- 8442961 TI - The effect of nalbuphine and droperidol on spontaneous movements during induction of anesthesia with propofol in children. AB - STUDY OBJECTIVE: To investigate the effects of droperidol and nalbuphine on spontaneous movements during induction of anesthesia with propofol in children. DESIGN: Randomized, double-blind study. SETTING: Inpatient ear, nose, and throat (ENT) surgical clinic at the University Hospital of Geneva. PATIENTS: Forty-five children, ages 4 to 12 years, undergoing routine elective ENT surgery. INTERVENTIONS: Children were randomly assigned to receive either nalbuphine 0.1 mg/kg, droperidol 0.025 mg/kg, or isotonic saline 3 minutes before anesthesia induction. Induction was performed with a loading dose of propofol 3 mg/kg. MEASUREMENTS AND MAIN RESULTS: Spontaneous movements were observed in 33%, 87%, and 100% of patients in the nalbuphine, droperidol, and control groups, respectively. The movements were dystonic and choreiform in nature and were similar in all three groups. The frequency of spontaneous movements was significantly reduced (p < 0.05) in the nalbuphine group as compared with the droperidol and control groups. CONCLUSIONS: Nalbuphine, but not droperidol, decreases the frequency of spontaneous movements induced by propofol during induction of anesthesia in children; neither quality of induction and recovery nor interval between the end of propofol administration and tracheal extubation were modified by nalbuphine as compared with the control group. PMID- 8442962 TI - Modification of tonic-clonic convulsions by atracurium in multiple-monitored electroconvulsive therapy. AB - STUDY OBJECTIVE: To determine the effect of two different doses of atracurium on the modification of tonic-clonic convulsions in multiple-monitored electroconvulsive therapy (MMECT). To compare recovery time and adverse reactions of these doses. DESIGN: Clinical study. Anesthesiologist was blinded in the evaluation of post-electroconvulsive therapy (ECT) myalgia and other side effects. SETTING: University-affiliated veterans general hospital. PATIENTS: Two groups of twelve psychiatric inpatients who suffered from major depression or catatonic-type schizophrenia that failed to respond to tricyclic antidepressant therapy. INTERVENTIONS: Under single-channel, prefrontal electroencephalographic (EEG) monitoring, patients were given either 0.3 mg/kg or 0.5 mg/kg of atracurium intravenously (IV) after anesthetic induction with methohexital 1 mg/kg i.v. MEASUREMENTS AND MAIN RESULTS: Evoked electromyographic responses of the adductor pollicis muscle was obtained by train-of-four stimulation of the ulnar nerve at the wrist every 20 seconds. The first twitch depression (T1) of neuromuscular blockade was maintained within 11% to 25% (atracurium 0.3 mg/kg) or 0% to 10% (atracurium 0.5 mg/kg) of control during the entire session of MMECT. Patients pretreated with atracurium 0.5 mg/kg had significantly fewer ECT-induced moderate and vigorous convulsions when compared with patients receiving atracurium 0.3 mg/kg (16.7% vs. 78.4%, moderate; 0% vs. 8.3%, vigorous). However, patients pretreated with atracurium 0.5 mg/kg took a longer time to attain a T4 ratio of 0.5 than did patients receiving atracurium 0.3 mg/kg (9.2 +/- 0.8 minutes vs. 4.3 +/- 0.4 minutes). There was no significant difference between the two groups with respect to cumulative seizure duration or frequency of bradycardia, sialorrhea, postseizure myalgia, nausea, headache, or confusion. No patient in either group recalled any event concerning electroconvulsive shock. CONCLUSIONS: Whereas full neuromuscular blockade by atracurium 0.5 mg/kg i.v. is very effective in the modification of tonic-clonic convulsions induced by ECT, we suggest that a lower dose of atracurium (0.3 mg/kg i.v.) be used if one needs to ascertain the occurrence of ECT-induced seizures as indicated by minimum peripheral muscle activity at the time of EEG recording during MMECT. PMID- 8442963 TI - A double-blind, placebo-controlled pilot study examining the effectiveness of intravenous ondansetron in the prevention of postoperative nausea and emesis. AB - STUDY OBJECTIVE: To compare the efficacy and safety profiles of ondansetron and a placebo when infused immediately prior to anesthesia induction for the prevention of postoperative nausea and emesis (vomiting or retching). DESIGN: Randomized, double-blind, placebo-controlled, parallel, multicenter pilot study. SETTING: Three U.S. ambulatory surgical facilities. PATIENTS: One hundred eighty ASA physical status I and II women scheduled to undergo ambulatory gynecologic surgical procedures while receiving general endotracheal anesthesia. INTERVENTIONS: Ondansetron 8 mg or a placebo (equivalent volume) was given intravenously (IV) prior to anesthesia induction to prevent postoperative nausea and vomiting. MEASUREMENTS AND MAIN RESULTS: For the first 24 hours following emergency from anesthesia, patients were monitored in the postanesthesia care unit by a research observer and at home via telephone contact and diary cards. More patients in the ondansetron group (62%) than in the placebo group (40%) were emesis-free over the 24-hour study period (p = 0.005). Ondansetron also was more efficacious than the placebo over the 24-hour study period when a surgery duration of more than 45 minutes was considered in the analyses. For all patients, regardless of surgery duration, there was a low degree of nausea during the course of the study. In all instances, the degree of nausea was slightly lower for ondansetron-treated patients than for placebo-treated patients; however, in no instances were the differences statistically significant. Ondansetron and placebo had similar safety profiles as established by laboratory test results, vital sign monitoring, and adverse event reporting. CONCLUSION: Ondansetron, infused IV before anesthesia induction, appears to be safe and effective when used in the prevention of postoperative nausea and emesis. PMID- 8442964 TI - A randomized, double-blind pilot study examining the use of intravenous ondansetron in the prevention of postoperative nausea and vomiting in female inpatients. AB - STUDY OBJECTIVE: To compare the efficacy and safety profiles of intravenous (IV) ondansetron (two 8 mg doses 8 hours apart) and a placebo when used in the prevention of postoperative nausea and emesis (vomiting or retching). DESIGN: Randomized, double-blind, placebo-controlled, parallel, multicenter pilot study. SETTING: Four university hospitals in the United States. PATIENTS: Two hundred seven women scheduled to undergo inpatient surgical procedures during general anesthesia. INTERVENTIONS: Patients were randomized to receive, in a double-blind fashion, either two 8 mg doses of IV ondansetron or a placebo. The first study drug dose was administered before induction of anesthesia; the second dose was given 8 hours later. Each study drug dose was admixed with normal saline to 20 ml and administered IV over 2 to 5 minutes. Vital signs were monitored immediately before and 1 minute after completion of the study drug infusion. MEASUREMENTS AND MAIN RESULTS: For the 24-hour period following operation, 60% of the patients who received ondansetron and 26% of the patients who received the placebo were emesis free (p < 0.001). Subanalyses based on patients' previous history of general anesthesia indicated that ondansetron was superior to the placebo in preventing emesis regardless of history [66% vs. 33% in patients who had never had general anesthesia or had had no nausea or emesis following previous anesthesia (p = 0.001) and 50% vs. 17% in patients who had nausea or emesis following previous anesthesia (p = 0.005)]. Ondansetron also was superior to the placebo for the prevention of nausea over the 24-hour study period regardless of anesthesia history. Ondansetron was generally well tolerated. The adverse event, vital sign, and clinical laboratory test profiles were similar to those for the placebo. No patient who received ondansetron had untoward changes in central nervous system function, including sedation. CONCLUSIONS: Prophylactic IV ondansetron appears to be safe and causes a significant reduction in the frequency and severity of postoperative nausea and emesis. PMID- 8442965 TI - Propofol-nitrous oxide versus thiopental sodium-isoflurane-nitrous oxide for strabismus surgery in children. AB - STUDY OBJECTIVES: To assess the quality of anesthesia and recovery and the frequency of postanesthetic retching and vomiting with propofol anesthesia for pediatric strabismus surgery. DESIGN: Randomized, open, prospective study. SETTING: University hospital. PATIENTS: Forty children scheduled for strabismus surgery. INTERVENTIONS: The 40 patients were all premedicated with oral midazolam and received intraoperative opioids. They were divided into two groups: Twenty children received propofol at induction, followed by maintenance of anesthesia with propofol infusion and an oxygen-nitrous oxide (O2-N2O) mixture. The other 20 children received thiopental sodium at induction, followed by isoflurane in an O2 N2O mixture. MEASUREMENTS AND MAIN RESULTS: At induction, pain and spontaneous movements were seen significantly more with propofol (11 of 20 vs. 0 of 20 for pain and 13 of 20 vs. 0 of 20 for spontaneous movements; p < 0.001), whereas thoracic rigidity was observed only with thiopental sodium (4 of 20). During maintenance of anesthesia, significantly more oculocardiac reflexes were seen with propofol (10 of 20 vs. 3 of 20; p < 0.02). The interval between termination of anesthesia and extubation was significantly shorter with propofol (13 minutes vs. 16 minutes; p < 0.02). For the first 24 hours after surgery, significantly less retching and vomiting were observed in the propofol group (4 of 20 vs. 11 of 20; p = 0.02). CONCLUSIONS: Propofol induction and maintenance of anesthesia for strabismus surgery in children significantly lowers the frequency of postanesthetic retching and vomiting, but propofol is associated with pain and spontaneous movements at induction and a high frequency of oculocardiac reflexes during maintenance infusion. PMID- 8442966 TI - Headache prevention following accidental dural puncture in obstetric patients. AB - STUDY OBJECTIVE: To evaluate the efficacy of a prophylactic saline patch and a prophylactic blood patch in prevention of headache following accidental dural puncture in obstetric patients. DESIGN: Prospective, randomized, single-blind study on dural puncture headache occurrence and cessation. SETTING: Inpatient obstetric unit at a metropolitan medical center. PATIENTS: Seventy-four inpatients who underwent vaginal delivery or cesarean section following accidental dural puncture during administration of epidural anesthesia for labor and delivery. INTERVENTIONS: Group 1 (n = 24), the control group, received fluids and analgesics. Group 2 (n = 30) received prophylactic epidural saline (40 to 60 ml) through the epidural catheter following completion of the obstetric procedure. Group 3 (n = 20) received autologous blood (15 ml) via epidural catheter following completion of the obstetric procedure. MEASUREMENTS AND MAIN RESULTS: In Group 1, 21 of 24 patients (87.5%) developed headaches, with conservative management. In Group 2, 20 of 30 patients (66.7%) developed headaches, and in Group 3, 1 of 20 patients (5%) developed a headache. CONCLUSIONS: The results of this study suggest that the administration of a prophylactic epidural blood patch is highly effective in the prevention of headaches following dural puncture, with headache frequency reduced from 87.5% to 5%. PMID- 8442967 TI - The effects of epidural anesthesia on ventilatory response to hypoxia. AB - STUDY OBJECTIVE: To evaluate the effects of epidural morphine on the ventilatory response to hypoxia in patients having abdominal surgery and to compare the effects of epidural lidocaine. DESIGN: Open-label, randomized study. SETTING: Shimane Medical University Hospital, Shimane, Japan. PATIENTS: Sixteen consenting, unpremedicated ASA physical status I and II patients undergoing abdominal surgery. INTERVENTIONS: Patients were administered 2 mg of morphine diluted in 10 ml of saline or 10 ml of 2% lidocaine from an epidural catheter that was inserted the day before surgery. MEASUREMENTS AND MAIN RESULTS: On the day before surgery, ventilatory parameters consisting of minute expiratory volume (VE), tidal volume (VT), respiratory frequency (f), and oxygen saturation by pulse oximeter (SpO2) were measured during resting state and hypoxic challenge. The same measurements were repeated 30 minutes after the epidural injection before surgery. The slope of VE/SpO2 decreased significantly from 1.6 +/- 0.3 to 1.2 +/- 0.2 after epidural morphine, although ventilatory values such as f, VT, VE, and PaCO2 were unchanged. Epidural lidocaine produced no significant changes in ventilatory response. CONCLUSION: Epidural anesthesia with morphine, but not lidocaine, reduced the ventilatory response to hypoxia indicated by VE/SpO2. PMID- 8442968 TI - The synergistic effect of two different nondepolarizing muscle relaxants on intraocular pressure. AB - STUDY OBJECTIVES: To evaluate the synergistic effect of neuromuscular blockade, produced by administering a priming dose of d-tubocurarine before or after pancuronium bromide, on endotracheal intubating conditions, intraocular pressure (IOP), and hemodynamic changes 1 minute following injection of intubating doses. To compare the results with equipotent doses of the individual muscle relaxants administered as a single bolus dose or in divided doses. DESIGN: Randomized study. SETTING: University medical center. PATIENTS: Ninety ASA physical status I and II inpatients (45 males, 45 females) assigned to one of six comparable groups (A-F). INTERVENTIONS: One hour after premedication, either normal saline (Groups A and B) or a priming dose of either d-tubocurarine (Groups C and F) or pancuronium (Groups D and E) was given intravenously (IV). Three minutes later, anesthesia was induced with 6 mg/kg of 2.5% thiopentone i.v. Then an intubating dose of pancuronium (Groups A, C, and E) or d-tubocurarine (Groups B, D, and F) was administered. The total dose given was equal to d-tubocurarine 0.4 mg/kg or pancuronium 0.07 mg/kg. Patients were intubated 1 minute after injection of an intubating dose of either relaxant. MEASUREMENTS AND MAIN RESULTS: IOP was measured with a Perkins applanation tonometer and blood pressure (BP) by a sphygmomanometer. Heart rate was derived from the electrocardiogram. Intubating conditions were scored according to given intubation criteria. Measurements were obtained at different times before and after intubation. In those patients given only one muscle relaxant for intubation either divided into priming and intubating doses or preceded by normal saline (Groups A, B, E, and F), there was a significant increase in IOP in response to intubation as compared with baseline (p < 0.05). In contrast, when d-tubocurarine was used as the priming drug for pancuronium blockade (Group C), IOP was significantly reduced in response to intubation, despite a concomitant increase in BP (p < 0.05). No significant change in IOP was observed when pancuronium was used as the priming drug for d tubocurarine blockade (Group D). Although good to excellent intubating conditions were reported in Groups C and D, poor intubating conditions were reported when the priming muscle relaxant was the same as the relaxant used to intubate. CONCLUSIONS: A smooth, rapid-sequence intubation with a concomitant reduction in IOP as required for open-eye, full-stomach patients can be achieved with a judicious mixture of nondepolarizing muscle relaxants as described for d tubocurarine and pancuronium in Groups C and D. PMID- 8442969 TI - Neuromuscular effects of succinylcholine following different pretreatments. AB - STUDY OBJECTIVE: To study the neuromuscular effects (onset, intensity, and duration of block) of succinylcholine following different pretreatments. DESIGN: Randomized open study. SETTING: University-affiliated hospital. PATIENTS: Fifty ASA physical status I and II adult inpatients undergoing elective ophthalmic surgery. INTERVENTIONS: Succinylcholine 0.5 mg/kg was administered after no pretreatment or after pretreatment with d-tubocurarine 0.05 mg/kg intravenously (IV) 3 minutes before, chlorpromazine 0.1 mg/kg i.v. 3 minutes before, alpha tocopherol (vitamin E) 600 mg in three divided doses orally at 6-hour intervals, or aspirin 600 mg orally 1 hour before in groups of ten patients each. MEASUREMENTS AND MAIN RESULTS: Neuromuscular block by stimulation of the ulnar nerve at the wrist by application of train-of-four stimuli at 2 Hz every 12 seconds and recording the force of contraction of the adductor pollicis muscle. There was no significant difference in the time to occurrence of maximum block (49 to 53 seconds), reappearance of the twitch response (254 to 307 seconds), or complete recovery of twitch response (532 to 607 seconds) between the groups receiving no pretreatment and those pretreated with chlorpromazine, alpha tocopherol, or aspirin. However, the time to maximum block (71 seconds) was significantly longer and the time to reappearance of the response (172 seconds) was significantly shorter (both p < 0.05) in the d-tubocurarine pretreated group in comparison with the control group. The time to complete recovery (420 seconds) also was shorter but not significantly different. CONCLUSIONS: Of the pretreatments used, only d-tubocurarine interferes with the neuromuscular blocking effects of succinylcholine. Chlorpromazine, which attenuates the muscle pains as well as the increase in creatine kinase and can be administered with the same convenience, may be a better pretreatment in the prevention of side effects of succinylcholine. PMID- 8442970 TI - Oral clonidine blunts the hemodynamic responses to brief but not prolonged laryngoscopy. AB - STUDY OBJECTIVE: To determine whether a 300 micrograms dose of oral clonidine given 90 minutes prior to laryngoscopy and intubation provides hemodynamic protection from the stress of a brief (15-second) and/or a prolonged (45-second) laryngoscopy. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Inpatients and outpatients scheduled for general anesthesia with intubation at a university-affiliated medical center. PATIENTS: Forty patients who gave informed, written consent to receive either an oral placebo or clonidine 5 micrograms/kg (up to a maximum dose of 300 micrograms) 90 minutes prior to induction of anesthesia and to undergo either brief or prolonged laryngoscopy prior to intubation. INTERVENTIONS: The patients underwent a standardized induction sequence that included d-tubocurarine 3 mg, thiopental sodium 5 mg/kg, and succinylcholine 1.5 mg/kg. The four treatment groups (each n = 10) included (1) placebo with 15-second laryngoscopy, (2) placebo with 45-second laryngoscopy, (3) clonidine with 15-second laryngoscopy, and (4) clonidine with 45-second laryngoscopy. Heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were mechanically obtained and recorded at 1-minute intervals for 12 minutes. MEASUREMENTS AND MAIN RESULTS: There were no differences between groups in the premedication hemodynamic measurements. Within each group, maximal hemodynamic variables increased significantly over the corresponding baseline values for that group. In the 15-second, but not the 45-second, laryngoscopy, clonidine successfully blunted the maximum SBP and DBP obtained when compared with the corresponding control group. In both the 15- and 45-second clonidine groups, maximum HR was significantly lower than in the corresponding placebo groups. CONCLUSIONS: Oral clonidine, when used as a preoperative medication, affords hemodynamic protection to patients undergoing a 15-second laryngoscopy. However, the stress of a 45-second laryngoscopy may be too great or the 300 micrograms dose of clonidine too low to provide hemodynamic protection for patients in this group. PMID- 8442971 TI - A comparison of midazolam, diazepam, and placebo as oral anesthetic premedicants in younger children. AB - STUDY OBJECTIVES: To validate the superiority of higher-dose oral midazolam as an anesthetic premedicant in children 6 years of age and younger, to determine whether less expensive diazepam is a viable alternative oral premedicant in this age-group, and to assess the preoperative oxygenation effects of both benzodiazepines. DESIGN: A prospective, randomized, double-blind study. SETTING: Outpatient surgery department and operating room (OR) of a freestanding children's hospital. PATIENTS: Seventy-five ASA physical status I and II outpatients 1 to 6 years of age. INTERVENTIONS: Patients were randomized to receive either midazolam 0.6 mg/kg, diazepam 0.3 mg/kg, or a placebo orally in a timely manner prior to surgery. MEASUREMENTS AND MAIN RESULTS: Each child's subsequent reaction to separation from his or her parents in the presurgical holding area was scored on a three-point behavioral scale. Once in the OR, an initial room air oxygen saturation by pulse oximeter (SpO2) was obtained. Each child's initial acceptance of the anesthetic induction mask was then scored on a four-point scale. No significant differences in parental separation scores, initial room air SpO2, or postanesthesia care unit admission time were observed among the three study groups. However, both midazolam and diazepam were observed to be superior to the placebo in facilitating the initial acceptance of the anesthetic induction mask. CONCLUSIONS: Even without premedication, a majority of children did not react negatively to an impending anesthetic. Therefore, neither midazolam nor diazepam appears to be necessary in most children younger than 6 years of age. Rather than implementing the routine use of an oral preoperative sedative, the challenge appears to be the selective identification of those children at risk for preanesthetic difficulties and psychological trauma. PMID- 8442972 TI - Anesthetic management of a morbidly obese woman with a massive ovarian cyst. AB - Morbid obesity affects 3% to 5% of the U.S. population and poses challenging problems to the anesthesiologist during the perioperative period. We present a unique case of the management of a morbidly obese woman complicated by a massive ovarian cyst. The major cardiopulmonary, metabolic, and technical features special to this patient population are discussed. PMID- 8442973 TI - Successful treatment of an episode of malignant hyperthermia using a large dose of dantrolene. AB - This clinical case report describes the use of extremely high doses of dantrolene in the management of an episode of malignant hyperthermia (MH). A 6-year-old, 25 kg girl underwent anesthetic induction with halothane for an elective inguinal herniorrhaphy. Tachydysrhythmias, laryngospasm, opisthotonos, rhabdomyolysis, and profound metabolic acidosis ensued as features of an MH crisis. Initial dantrolene administration did not alleviate the symptoms. Increasing doses of dantrolene eventually totaling 42 mg/kg, along with symptomatic supportive care, were administered successfully to treat the event. It is postulated that the severe muscle rigidity may have precluded the circulation of dantrolene to its site of action. The role of the Malignant Hyperthermia Association of the United States (MHAUS) Hotline as a 24-hour consultative service is noted. PMID- 8442974 TI - Atrial septal lipomatous hypertrophy and ischemic heart disease: an unusual presentation. AB - Lipomatous hypertrophy of the interatrial septum consists of the abnormal accumulation of fatty tissue. We report a patient with unsuspected massive lipomatous hypertrophy of the interatrial septum scheduled to undergo coronary artery surgery. This patient had experienced atrial arrhythmias and obstructive symptoms preoperatively that were ascribed to her coronary artery disease (CAD). The perioperative anesthetic and surgical management of patients with lipomatous hypertrophy of the interatrial septum and CAD is discussed. PMID- 8442976 TI - Extensive patch tracheoplasty with a silicon "T" tube stent in a 7-month-old infant. AB - Congenital tracheal stenosis is difficult to manage. We describe the combination of an extensive patch tracheoplasty and silicon "T" tube stenting performed in a 7-month-old infant following classical repair of a coexisting pulmonary artery sling. PMID- 8442975 TI - Administrative guidelines for response to an adverse anesthesia event. The Risk Management Committee of the Harvard Medical School's Department of Anaesthesia. AB - The Risk Management Committee of the Harvard Medical School's Department of Anaesthesia developed a set of guidelines recommending administrative actions that should be taken immediately following an adverse anesthesia event. The guidelines are intended to limit patient injury from a specific event associated with anesthesia and to ensure that the causes of the event are identified to prevent recurrence. The guidelines direct the primary anesthetist to concentrate on continuing care but quickly notify someone in a leadership position, who would become the "incident supervisor." The incident supervisor would be knowledgeable of the details of the protocol and direct activities for ensuring appropriate medical care, sequestration of equipment, documentation of information, and contact of other appropriate administrative personnel. Experience with the guidelines has shown that they can be effective if applied but that it is difficult to do that consistently in our large medical centers. PMID- 8442977 TI - Tumor embolus in lung surgery. A case report and review of the literature. AB - A 71-year-old man underwent a completion pneumonectomy for a recurrent carcinosarcoma of the left upper lobe. A single lumen endotracheal tube was used for intubation. During dissection the right main bronchus became blocked by a tumor mass. Due to severe adhesions it was impossible to open the airway from inside the operation field. This neither was also not possible by bronchoscopic maneuvers and the patient died. The case is similar to six cases described in the literature since 1966 [4-7, 9, 10]. Recommendations for preventing and treating the complications are given. PMID- 8442978 TI - Systolic sequential flow velocity profiles in four currently used bileaflet heart valve prostheses. PMID- 8442979 TI - Myocardial oxygen consumption and lactate production during antegrade warm blood cardioplegia. PMID- 8442980 TI - The burst of the balloon. The Mansfield Scientific Balloon Aortic Valvuloplasty Registry. PMID- 8442981 TI - Orthotopic heart transplantation for congenital heart disease. Technical considerations. AB - Heart transplantation for congenital heart disease poses unique problems because of structural anomalies and previous corrective and palliative surgery. In the period between May 1985 and February 1992 a total of 231 orthotopic heart transplants were performed at our hospital -22 of these procedures were carried out in patients with congenital heart disease. The patient's ages ranged from 1 month to 51 years (median 10 years). There were 13 patients in the paediatric group (under 16 years) and 9 patients in the adult group (16 years or older). The diagnoses included univentricular connections (8 patients), complex morphology (4 patients), congenitally corrected transposition of the great arteries (TGA) (3 patients), hypoplastic left heart syndrome (2 patients), Fallot's tetralogy, tricuspid atresia, TGA, pulmonary atresia with intact ventricular septum and atrial septal defect (ASD) and ventricular septal defect (VSD). These patients had protected pulmonary circulation due to previous surgery or as a result of intrinsic pulmonary stenosis. Seventeen patients (77%) had undergone 29 prior operations (21 palliative and 8 corrective) including Blalock-Taussig shunts, pulmonary artery (PA) banding, ASD and VSD repair, Fontan procedure and Mustard operation. There were 2 early deaths in the paediatric group and 4 early deaths in the adult group, but no late deaths. The cause of death was multi-organ failure following uncontrollable haemorrhage in 3 patients, sepsis in 1 patient and donor organ failure in the 2 paediatric patients. Specific surgical manoeuvres were required to create the normal anatomical configuration. These included the rerouting of venous circulation, pulmonary artery reconstruction and atrial septation. Adequate donor tissue was taken to permit satisfactory reconstruction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8442982 TI - Closed circuit perfusion of an isolated rabbit lung. A new model for the evaluation of preservation quality of stored lungs. AB - The comparison of different preservation methods in lung transplantation demands a well standardized and reproducible animal model. The aim of this study was to establish as in vitro model in which the oxygenation capacity of the lung can be investigated over an extended period of time. Heart-lung blocks from 6 New Zealand white rabbits were harvested, the pulmonary artery and the left ventricle cannulated and the lungs perfused with whole rabbit blood by means of a roller pump and ventilated with room air. A dialyser was installed into the closed circuit perfusion for continuous deoxygenation of the oxygen-saturated blood gained from the left ventricle. Throughout the stable perfusion period the average arterial and venous partial oxygen pressure (pO2) levels were 105.8 +/- 15.5 mmHg and 55.2 +/- 6.2, respectively (P < 0.05). The average peak airway pressure steadily increased from 10.7 +/- 1.2 mmHg at the start of reperfusion to 21 +/- 14.4 mmHg after 180 minutes (P = NS). With this experimental setting it is possible to maintain stable conditions (i.e. constant venous and arterial blood gases) for at least 180 minutes. It is therefore feasible to compare the influences of different preservation methods on the quality of lung function. PMID- 8442983 TI - The effect of fibrin glueing to seal bronchial and alveolar leakages after pulmonary resections and decortications. AB - In order to investigate the effect of fibrin glueing on the treatment or prevention of air leakages, 114 patients undergoing pulmonary resections and pneumonectomies were studied in two treatment groups: surgery alone (59 patients) or analogous surgical treatment followed by the application of fibrin glue (55 patients). The patients were randomly assigned to treatment groups within two strata: pulmonary resections (63 patients) and pneumonectomies (51 patients). Intraoperatively, 81% of the patients undergoing pulmonary resection who suffered from air leakages after conventional suturing showed improved results of the airway-tolerance-pressure test after the application of fibrin glue (one-sided P value < 0.01; 95% confidence interval: 58-95%). Treatment with fibrin glue reduced the incidence of postoperative leakages significantly from 66% in the control group to 39% in the treatment group (one-sided P-value < 0.02; estimated risk reduction 41%; 95% confidence interval 2-65%). An additional reduction of the duration of post-operative air leakages by the treatment with fibrin glue could not be shown. In terms of minor response criteria, slight trends for an advantage of treatment with fibrin glue could be observed for the duration of stay in hospital and the number of patients with complications. There were no obvious trends concerning fever, intraoperative and postoperative intubation times, the amount of secretion from thoracic tubes and the general condition of the patients. No adverse drug event related to fibrin glueing was observed. PMID- 8442984 TI - Prevention of adhesion formation around the internal mammary artery pedicle by Gore-Tex surgical membrane. An experimental study in goats. AB - The effects of wrapping the internal mammary artery in Gore-Tex surgical membrane on the formation of adhesions were investigated. In seven goats both internal mammary arteries were dissected free from the thoracic wall. In six goats the internal mammary arteries were wrapped in Gore-Tex surgical membrane. In the remaining animal both arteries were removed and used as controls. After 6 months the goats were reoperated and it was found that the wrapped segments of all arteries were completely free of adhesions, whereas the non-wrapped segments showed severe adhesion formation. Histologic examination could not detect differences between the wrapped arteries and the controls. One of the 12 wrapped arteries was occluded by a longer existing thrombus, which is attributed to the surgical technique and the fact that postoperatively no anticoagulation was given. The beneficial effect of the use of Gore-Tex surgical membrane on the prevention of adhesion formation is excellent and this implies that it could be used in coronary artery bypass operations, thus reducing the chance of damage to the bypass in case of reoperation. PMID- 8442985 TI - Six-year follow-up after heart valve replacement with the Edwards Duromedics bileaflet prosthesis. AB - The Duromedics Edwards valve (DE) was designed with a self-irrigating hinge mechanism to reduce the rate of thromboembolic complications. This report presents a prospective follow-up of patients after valve replacement with this prosthesis in a university hospital. Five hundred seven patients had DE prostheses implanted in the aortic (n = 268), mitral (n = 183) or aortic and mitral positions (n = 56). The perioperative mortality was 6.9%. Follow-up was 98% complete, comprising 2009 patient years for a mean follow-up of 48 months: (range 27-84). The actuarial freedom from complications is calculated as follows (linearized rates in parentheses): late mortality 81.0 +/- 2.3% (3.4%/patient year), thromboembolism 93.5 +/- 1.5% (1.1%/patient year), anticoagulation-related hemorrhage 89.5 +/- 2.0% (1.9%/patient year), prosthetic valve endocarditis 96.0 +/- 1.2% (0.7%/patient year), valve-related mortality 93 +/- 1.8% (1.5%/patient year), valve failure 89 +/- 2.0% (2%/patient year), treatment failure 88.0 +/- 2.0% (2.2%/patient year) and all valve-related morbidity and mortality 74.0 +/- 2.8% (5.3%/patient year). Two events of leaflet escape were observed in the study group (0.09%/patient year). Both patients were reoperated successfully. Mechanical hemolysis was subclinical in all cases. The DE shows a complication rate comparable to other modern mechanical valve prostheses. After solving the problem of durability, reconsideration of this valve is worthwhile due to its low risk of thromboembolic complications. PMID- 8442986 TI - Total arterial myocardial revascularization. AB - The superiority of the internal thoracic artery (ITA) compared with venous conduits in terms of late graft patency is nowadays well documented. The inferior epigastric artery (IEA) was recently proposed as an alternative conduit for coronary artery surgery with good early clinical and angiographic results. To improve the benefits from myocardial revascularization, we expanded the use of these arterial conduits. From June 1988 to December 1991, 615 patients underwent coronary surgery in our institute. In 138 of them (22.4%) we performed total arterial myocardial revascularization placing 2 or more coronary anastomoses. An average of 2.37 anastomoses per patient were placed with the maximum number of 6 in one case. Only one patient died of cardiac related causes (0.72%). Perioperative morbidity included myocardial infarction and sternal dehiscence in 5 patients each (3.6%). No stroke or reoperation for bleeding occurred. No rectus muscle necrosis was recorded. Accurate preoperative planning of graft placement allows for the performance of as many as 6 distal anastomoses using bilateral ITA and single IEA grafts only, thus completely revascularizing most of the hearts with three-vessel disease. In our series this procedure was not reflected in an increase in the perioperative morbidity. We choose an elective total arterial revascularization in younger (under 65 years) patients who, while showing a lower incidence of complications in our study, are likely to derive the highest benefits from the good durability of ITA and hopefully IEA grafts. PMID- 8442987 TI - Use of biventricular circulatory support as bridge to simultaneous heart and kidney transplantation. AB - A 64-year-old man with dilated cardiomyopathy and chronic renal insufficiency (without dialysis) was admitted in cardiogenic shock urgently requiring a circulatory biventricular assist device (Thoratec). Twenty-nine days later we performed orthotopic cardiac and heterotopic renal transplantations with organs from the same donor. Postoperatively secondary renal insufficiency occurred due to rejection of the graft, bleeding ulcer with hypovolemic shock, and peritonitis due to Streptococcus faecalis and Candida. In the postoperative course only one rejection of the cardiac graft was detected. The patient was discharged after 4 months, resuming a normal life. PMID- 8442988 TI - [Non-valvular auricular fibrillation and cerebral infarction]. PMID- 8442989 TI - [Neuromuscular diseases and anesthesia]. PMID- 8442990 TI - [Selective demyelination of the corpus callosum non associated with alcoholism or malnutrition]. PMID- 8442991 TI - [Spontaneous intrapetrous dissection of the internal carotid in muscular fibrodysplasia]. PMID- 8442992 TI - [Chronic cervical myelopathy caused by irradiation. Diagnostic value of magnetic resonance]. PMID- 8442993 TI - [Calf hypertrophy following S1 radiculopathy]. PMID- 8442994 TI - [Hypophyseal apoplexy: clinico-radiologic analysis and clinical course in 18 patients]. AB - The period of time between clinical manifestations and admission of 18 patients with pituitary apoplexy (PA) was of a mean of 6 days with the exception of two cases. Distribution by age and sex, absence of previous endocrinal clinical manifestations in 38.8% of the patients was similar to that of larger series described. Headache constituted an almost constant symptom. The most affected cranial pairs were II (12 patients), III and IV, both in 8 cases. Following decompression surgery, great improvement was observed in visual acuteness in 5 of these patients, and in the ophthalmoplexy in 8. Alterations in the level of consciousness is less and less frequent in the context of PA thanks to the diagnosis of less severe clinical episodes. Similarly, a high rate of clinical suspicion and the use of new imaging techniques (NMR) have contributed notably with the most outstanding findings being resumed. Moreover, a case of PA with associated intracranial aneurysm verified by carotid angiography is described. PMID- 8442995 TI - [Drug-resistant focal epilepsy with normal cranial CT. Electroclinical correlation and magnetic resonance in 45 patients]. AB - Forty-five patients between 15 and 60 years of age with pharmacoresistant focal epilepsy of more than 4 years duration with normal cranial CT were analyzed. Magnetic resonance and sleep EEG were performed. In 82% of the patients epilepsy had initiated prior to 20 years of age with 89% having partial complex crises and 75% also having secondary generalized crises. EEG demonstrated abnormalities in the temporal lobe in 78% of the cases. Activation of the abnormalities was observed during REM sleep in 24% of the patients. MR was pathologic in 38%, with the most frequent finding corresponding to a sole hyperintense T2 signal (76%). A good correlation was observed between the electroclinical findings and MR in 72% of the cases with pathologic MR. Most of these patients should, thus, be considered as candidates for surgical evaluation of their epilepsy. PMID- 8442996 TI - The effect of aging and ovariectomy on the vertebral bone mass and biomechanical properties of mature rats. AB - Ovariectomy has a proven pronounced effect on bone mass, as has been shown in several animal models and in clinical studies. The aim of this study was to investigate the effect of ovariectomy on both vertebral bone mass and biomechanical competence. The study was performed on a long-term mature rat model. One hundred and five, three-month-old female Wistar rats were randomized into seven groups. One group was killed at the start of the study and was used as a baseline group. Three groups were ovariectomized and followed for one, three, or six months after the operation. Three groups were sham-operated and followed for the same periods. At death, three lumbar vertebrae were obtained from each rat, and changes in bone mass (ash content, trabecular bone volume (TBV)), bone structure, and biomechanical competence were assessed from these vertebrae. The results revealed an age-related (three-nine months) increase in bone mass and biomechanical competence in the sham-operated control groups. In the ovariectomized groups, an age-related decrease in TBV was disclosed. The ash content remained constant, whereas the biomechanical parameters--after an initial increase--showed decreasing values with age in the ovariectomized groups. When age-matched control and ovariectomized rats were compared, an increasing difference in both bone mass and bone biomechanical competence was disclosed. The study has shown that ovariectomy has a pronounced effect not only on vertebral bone mass, but also on bone quality, and that this mature rat model forms an excellent basis for evaluating potential therapeutic regimens for the treatment of osteoporosis. PMID- 8442997 TI - Platelet activating factor increases intracellular calcium in isolated osteoclasts but does not modify bone resorption. AB - Platelet activating factor (PAF) is an inflammatory mediator secreted by activated macrophages and granulocytes. Since PAF has been previously demonstrated to increase intracellular calcium in isolated osteoclasts, the effect of PAF on bone resorption was examined. This was compared to effects seen after addition of calcium ionophores and calcitonin, an inhibitor of bone resorption, in order to determine if an increase in [Ca++]i inhibits osteoclast mediated resorption. The results demonstrate that PAF has no effect on either unstimulated or PTH-induced bone resorption. Calcium ionophores, ionomycin, and A23187, at concentrations that increased [Ca++]i, failed to modulate resorption in the fetal long bone assay. In addition, salmon calcitonin did not change [Ca++]i in spite of its strong inhibition of bone resorption. Taken together, these results demonstrate that the second messenger pathways involved in osteoclast downregulation can be independent of [Ca++]i, and may involve other messenger systems. PMID- 8442998 TI - The effects of growth hormone on fracture healing in rats: a histological description. AB - Previous biomechanical studies have indicated that growth hormone has a stimulatory effect on fracture healing. This study was designed to give a histological description of the long-term effects of growth hormone on fracture healing in rats. Sixty-four female rats were divided into two groups and were given either biosynthetic human growth hormone (2.7 mg/kg body weight/day) or saline s.c. in two daily injections. This treatment was given for 20 days after a closed tibial fracture with medullary nailing had been performed. Five or six rats were killed from each group after 10, 20, 30, 40, 50, and 80 days of healing. The fracture site was embedded undecalcified in methylmethacrylate, cut into 8 microns thick, mid-frontal sections, and investigated in a normal light microscope after staining with Masson Trichrome and in polarized light after staining with Sirius red. The results revealed that growth hormone had an initially stimulatory effect on external callus formation. However, the callus formed was loosely structured and was not removed by the normal modeling and remodeling process. The callus therefore persisted even after 80 days of healing. In contrast, after only 40 days the saline treated rats showed healing, with a resumption of the normal size and shape of the fractured tibial bone, leaving only a small amount of dense callus tissue. The study also revealed that the hemopoietic system was stimulated by growth hormone, with massive invasion of marrow cells into the external fracture callus. Bone marrow cells dominated the intratrabecular space in growth-hormone treated animals, even after 80 days of healing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8442999 TI - Bone mineral density measured by dual energy x-ray absorptiometry in patients with non-insulin-dependent diabetes mellitus. AB - Because of the previous controversial findings in diabetic patients with older methodologies, we assessed bone mineral density (BMD) in 78 patients (38 males and 40 females) with non-insulin-dependent diabetes mellitus using dual energy x ray absorptiometry (DEXA). BMD was measured in lumbar vertebrae (L2-4). The BMD of each patient was calculated as the percentage of the mean value (%BMD) obtained from a healthy control group matched for sex and age. The %BMD of the patients with diabetes was about 100% for females and 96% for males, as compared with BMD of normal controls. The %BMD of the patients with diabetes was significantly correlated with body mass index and urinary C peptide level, and inversely correlated with age and duration of diabetes within 20 years. No relationships were found between %BMD and serum calcium, phosphorus, or glycosylated hemoglobin A1C levels. These observations suggest that metabolic abnormalities associated with diabetes mellitus alter the BMD, and that such factors as duration of the disease and deficit in insulin secretion are risk factors for decreased BMD. PMID- 8443000 TI - An ultrastructural study of the mitotic preosteoblasts in the primary spongiosa of the rat mandibular condyle. AB - In this study, we observed mitotic preosteoblasts that have the structural features of osteoblasts in the primary spongiosa of the rat mandibular condyle. The rough endoplasmic reticulum and the Golgi apparatus showed remarkable disorganization during mitosis. The Golgi saccules were replaced by groups of large vacuoles and small vesicles. The cisternae of the rough endoplasmic reticulum also were vacuolized. Since this disorganization occurred in conjunction with the formation of the mitotic spindle, it is probably related to the changes of the microtubular cytoskeleton. Further, secretory granules were arrayed along the mitotic spindle microtubules at the metaphase, and concentrated around the midbody at the telophase. These findings indicate a close relationship exists between secretory granules and microtubules. PMID- 8443001 TI - Oral contraceptive pill use and fractures in women: a prospective study. AB - It has been suggested that use of the oral contraceptive pill by women confers protection against osteoporosis later in life. However, cross-sectional studies of bone density among pill users have yielded discrepant results. We therefore investigated the relationship between pill use and subsequent occurrence of fracture in a cohort of 46,000 women enrolled in the Royal College of General Practitioners Oral Contraception Study during 482,083 person-years of follow-up. Fracture risk was lower among multiparous women, non-smokers, and those of lower socio-economic class. The risk of subsequent fractures among the women who had ever used the oral contraceptive pill was significantly greater than that among women who had never used it (relative risk 1.20, 95% confidence intervals 1.08 1.34) after adjustment for these variables. When the analysis was confined to forearm fractures, no significant effect of pill use on fracture risk was detected. Although the study only includes limited observation of older women to date, these data do not support the hypothesis that pill use protects women against the occurrence of osteoporotic fractures in later life. PMID- 8443002 TI - Effects of two new vitamin D3 derivatives, 22-oxa-1 alpha-25-dihydroxyvitamin D3 (OCT) and 2 beta-(3-hydroxypropoxy)-1 alpha, 25-dihydroxyvitamin D3 (ED-71), on bone metabolism in organ culture. AB - We have tested two new vitamin D3 derivatives, 22-oxa-1 alpha, 25 dihydroxyvitamin D3 (OCT) and 2 beta-(3-hydroxypropoxy)-1 alpha, 25 dihydroxyvitamin D3 (ED-71), for their effects on bone metabolism compared with 1 alpha, 25-dihydroxyvitamin D3 (1,25(OH)2D3) in two organ-culture systems. In a previous study (Abe et al. 1987), it was reported that OCT had weak activity in stimulating bone resorption in vitro. In the present study, however, OCT stimulated bone resorption in cultured fetal rat long bones and inhibited collagen synthesis in cultured neonatal mouse calvariae in a dose-dependent manner with significant effects at 10(-10) M and maximal responses at 10(-8) M. Its potency and effectiveness were identical to 1,25(OH)2D3. On the other hand, ED-71, which has been found to prevent bone loss in vivo (Okano et al. 1989b), was less active in vitro. The activity of ED-71 at 10(-8) M on bone resorption was similar to 1,25(OH)2D3, but it did not stimulate resorption at 10(-10) M. Its inhibitory effect on collagen synthesis was weaker than for OCT of 1,25(OH)2D3. The activity of all three compounds on bone resorption was not inhibited by indomethacin or cortisol. 1,25(OH)2D3 and OCT significantly inhibited [3H] thymidine incorporation into mouse calvariae at 10(-9) M, while ED-71 inhibited [3H]-thymidine incorporation only at 10(-8) M. These results indicate that OCT and 1,25(OH)2D3 have similar effects on bone in organ culture. Pharmacokinetic differences may explain the marked difference in response to those two agents in vivo. ED-71 is less potent, particularly in inhibiting bone formation. Such differences may have importance in the development of vitamin D analogs for clinical use. PMID- 8443003 TI - Effects of platelet-derived growth factor isoforms on calcium release from neonatal mouse calvariae. AB - Platelet-derived growth factor (PDGF) is the major growth factor in serum for cells of mesenchymal origin and induces many different activities, including bone resorption. Since the initial report that PDGF stimulated calcium release from bone organ cultures, it has been shown that PDGF is a dimeric protein consisting of two disulfide bonded polypeptides encoded by different genes. Three isoforms of the two gene products have been isolated. We compared the capacity of each isoform to stimulate calcium release from radiolabeled mouse calvariae. PDGF-AB from human platelets and recombinant PDGF-BB isoforms significantly stimulated calcium release at 5 ng/ml, but not in lower doses. Recombinant PDGF-AA did not induce calcium release. Indomethacin blocked the stimulated bone resorption, suggesting a prostaglandin-mediated mechanism of action. PDGF-induced calcium release was compared to TGF-beta 1 in the organ culture system. Approximately a 10-fold greater concentration of PDGF-AB and PDGF-BB was required to achieve a similar degree of calcium release as found in TGF-beta 1 treated calvariae. Thus, TGF-beta 1, PDGF-AB, and PDGF-BB significantly stimulated calcium release from mouse calvariae. This response is specific in that PDGF-AA did not stimulate calcium release. PMID- 8443004 TI - Canine distemper virus transcripts detected in the bone cells of dogs with metaphyseal osteopathy. AB - Using the technique of in situ hybridisation, we have recently extended our observations that canine distemper virus (CDV) is present in the bone cells of patients with Paget's disease, and have shown that CDV is also detectable in the bone cells of dogs that are naturally infected with the virus. Since hybridisation was localised to bone cells within the metaphyses of the affected dogs, we investigated the possibility that CDV might be involved in the canine metaphyseal bone disorder, metaphyseal osteopathy. Bone samples from three cases of metaphyseal osteopathy were examined for the presence of the CDV nucleocapsid (CDV-N) gene and the measles virus nucleocapsid (MV-N) gene, using 35S-labelled sense and antisense riboprobes. As with our previous findings in Paget's disease of bone, only the antisense probe was found to hybridize to the osteoblasts and osteoclasts within the affected metaphyses. No hybridisation was seen with the CDV-N sense and MV-N probes in any of the samples tested. Bone samples were also taken from one of the cases to check for the presence of the CDV-N gene using the polymerase chain reaction (PCR). Our findings with in situ hybridisation were confirmed by PCR and subsequent Southern blotting and probing with a 32P-labelled cDNA probe. The detection of CDV RNA within the bone cells of dogs with metaphyseal osteopathy suggests that this virus may be a cause of the disease and provides further, indirect evidence that CDV might be responsible for the bony abnormalities seen in Paget's disease of bone. PMID- 8443005 TI - Andrew Rugg-Gunn takes on the BDJ. Interview by Kate O'Malley. PMID- 8443006 TI - Sarah's spots. PMID- 8443007 TI - 'The dentist's responsibility'. PMID- 8443009 TI - The transfer of patients from the Community Dental Service in Greater Glasgow Health Board area to the General Dental Service. AB - Between January and June 1990, 688 patients of Greater Glasgow Health Board Community Dental Service were asked to attend a General Dental Practitioner in future. At the end of June 1991, only 255 patients, 37% of the sample, were found to be registered on the General Dental Service Capitation Scheme. Registration was associated with the 'Neighbourhood Type' which is a reflection of the socioeconomic characteristics of the locality. Those living in the most favourable group of Neighbourhood Types were more likely to be registered with a General Dental Practitioner after leaving the Community Dental Service. PMID- 8443008 TI - Temporomandibular joint and orofacial pain: clinical and medicolegal management problems. AB - Idiopathic pain in the face, temporomandibular joint (TMJ), and teeth is common but varied in its duration and severity. Many cases respond to informed reassurance or simple physical therapy using an occlusal splint. Those that do not should be referred for specialist management by medication, and where necessary, arthroscopy or occasionally arthrotomy. Awareness of the underlying psychogenic factors is important at all levels of management, particularly as some patients will benefit from the support of a liaison psychiatrist. The failure to recognise these factors, together with prolonged unsuccessful physical or surgical therapy can render the pain intractable or incite certain patients to seek relief through litigation. PMID- 8443010 TI - Oral manifestations of poisoning. AB - The purpose of this paper is to describe the variety of chemical agents and medicines which can produce oral manifestations following poisoning. Rapid diagnosis is essential in covert cases to ensure early treatment. Furthermore, oral care is an important part of the general management of many poisoned patients. PMID- 8443011 TI - Readership survey results. AB - A key stage in the BDJ's current program of renovations was the readership survey, carried out last autumn. Broadly, the survey aimed to find out how dentists rated the old style BDJ against the other general interest UK journals, and how they viewed its content and design. PMID- 8443012 TI - A friend in need. PMID- 8443013 TI - The arts and sciences debate. PMID- 8443014 TI - Iatrogenic needle phobia. PMID- 8443015 TI - The Bloomfield debate. PMID- 8443016 TI - The future of vocational training. PMID- 8443017 TI - 'Hidden acids'. PMID- 8443018 TI - 'Recovery position'. PMID- 8443019 TI - 'Trends in the incidence of oral carcinoma in Northern Ireland 1975-89'. PMID- 8443020 TI - 'A problem with dentures'. PMID- 8443021 TI - Rationale and techniques of non-surgical pocket management in periodontal therapy. AB - Traditional views on pocket instrumentation in periodontal therapy have centred upon the thorough scaling and planing of root surfaces, which aim to remove all calculus and substantial amounts of 'necrotic' and 'contaminated' cementum. The lack of scientific evidence for removing calculus in periodontal therapy, was highlighted by Frandsen and recent studies have also questioned the need for extensive root planing to remove 'substantial' amounts of cementum. The need for some degree of pocket instrumentation during periodontal therapy however, is beyond doubt, as clinical studies on the efficacy of nonsurgical periodontal treatment published during the last decade have clearly shown. A review of this important topic is therefore timely and this paper aims to elucidate some of the concepts which are currently the subject of debate. A resume of the formation and characteristics of the subgingival environment is a necessary starting point. PMID- 8443022 TI - Diverticulum of the buccal mucosa: report of a case. PMID- 8443023 TI - Community dental service based out of hours emergency dental care--a pilot study. AB - Twenty-nine out-of-hours calls were received during the 6-week period. Advice was offered to 27 patients and two call-outs were made for treatment of acute abscesses in children. Eight patients claimed to be under treatment with the CDS, 17 claimed to be registered with a general dental practitioner, while four claimed not to be registered. A demand for an emergency service was demonstrated, as was the need to define accurately the categories of patients eligible for emergency treatment within the CDS. The pilot study also highlighted the requirement to fund this service adequately. PMID- 8443024 TI - Transforming beliefs into action: a professional practice model. PMID- 8443026 TI - Defining nursing administration terms (continued). PMID- 8443025 TI - Alert! Don't abbreviate zidovudine as AZT. PMID- 8443027 TI - The effects of anti-hypertensive medication on learning and memory. AB - 1. The aim of the study was to investigate whether there were differential effects of three different anti-hypertensive medications (cilazapril, atenolol, nifedipine) on cognitive function. 2. A sub-group of patients participating in a large clinical trial of these three drugs, randomly allocated between the three drug conditions, received cognitive assessment at two points before the commencement of treatment and then after 12 and 24 weeks of treatment. Seventy six patients began treatment, and 55 completed the full course. 3. Tests of learning and memory were designed specially for the study, with a different but comparable version administered on each assessment occasion, in a fixed order. 4. No significant differences between drug groups were found in any index of learning or memory, at any testing occasion. The results were the same whether or not treatment non-completers were included in the analysis. PMID- 8443028 TI - CNS-related performance and haemodynamics of metoprolol-Oros and propranolol after single and 3 days dosing in healthy volunteers. AB - 1. The effects of metoprolol-Oros 14/190 once daily, propranolol 80 mg twice daily and temazepam 10 mg once daily on central nervous system (CNS) related performance and haemodynamic variables were evaluated in a double-blind, randomized, placebo controlled, crossover study in 12 healthy volunteers. Drugs were administered for 3 consecutive days except for temazepam, which was administered on days 1 and 3 only. Treatment effects were evaluated at 0, 2, 5 and 8 h on days 1 and 3. 2. Neither beta-adrenoceptor blocker had significant effects in a battery of tests after single or 3 days dosing. Temazepam caused a decrease in saccadic peak velocity of 37.4 degrees s-1 (95% CI: 6.0, 68.9) at 2 h and an increase of auditory reaction times of 11.5 ms (0.2, 22.8) at 8 h on day 1. No significant effects of temazepam were detected on day 3. 3. Both beta adrenoceptor blockers reduced exercise heart rate. Peak effects were measured at 2 h 40 min after propranolol but not metoprolol-Oros (difference, day 1:20 (11, 29) beats min-1, day 3:13 (8, 19) beats min-1). Both beta-adrenoceptor blockers significantly reduced baseline exercise heart rate on day 3. Compared with day 1, metoprolol-Oros caused larger reductions of exercise heart rate at all times on day 3. 4. Metoprolol-Oros and propranolol caused similar reductions of systolic- and diastolic blood pressure on days 1 and 3. Temazepam caused a small reduction in diastolic blood pressure at 5 h 40 min on day 1 but was otherwise devoid of haemodynamic effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8443029 TI - Comparison of quinapril and atenolol as single drugs or in combination with hydrochlorothiazide in moderate to severe hypertensives, using automated ambulatory monitoring. AB - 1. Forty patients with moderate to severe hypertension and daytime ambulatory diastolic blood pressure > or = 90 mm Hg were randomized double-blind to once daily treatment with either quinapril up to 20 mg (n = 20) or atenolol up to 100 mg (n = 20) as single drugs or in combination with hydrochlorothiazide 25 mg over a period of 12 weeks. 2. Conventional and ambulatory blood pressure, heart rate, side effects and metabolic changes were compared at the end of the run-in period on placebo, after 4 weeks on monotherapy and at the end of the 12-week period of active treatment. 3. Quinapril and atenolol reduced conventional blood pressure equally with substantial additional effect seen on combination therapy. The two regimens induced a significant decrease in ambulatory BP. However, the atenolol treated ambulatory hypertensive group experienced significantly greater decreases in diastolic blood pressure during 24 h, awake and sleep periods than did the quinapril group. 4. Adverse reactions were mild with both drugs except for severe Raynaud phenomenon in one patient in the atenolol group. Triglyceride levels were significantly increased with atenolol alone and in combination with hydrochlorothiazide. 5. Thus, within the limits of the dose ranges tested, quinapril and atenolol as single drugs or in combination with hydrochlorothiazide reduce significantly conventional and ambulatory blood pressure in moderate to severe hypertensives, but atenolol is more effective in reducing ambulatory diastolic blood pressure. PMID- 8443030 TI - Effect of renal function on the pharmacokinetics and pharmacodynamics of trandolapril. AB - 1. The pharmacokinetics and pharmacodynamics of a single dose of trandolapril, an angiotensin converting enzyme (ACE) inhibitor with an active metabolite, trandolaprilat, which is in part further metabolised prior to renal elimination, were evaluated in 31 subjects with a wide range of renal function (creatinine clearance 4-112 ml min-1 1.73 m-2). 2. The pharmacokinetics of trandolapril were unaffected by differences in renal function. 3. In contrast, there was a close correlation between the renal clearance (0-96 h) of trandolaprilat and creatinine clearance (r = 0.95, P = 0.0001). The maximum plasma concentration of trandolaprilat, and the area under the concentration curve (0-96 h) correlated inversely with creatinine clearance (r = -0.59, P < 0.001; and r = -0.61, P < 0.001 respectively). 4. Significant changes in plasma trandolaprilat concentrations were seen only in patients with creatinine clearances of 30 ml min 1 1.73 m-2 or less, suggesting that a dose reduction in trandolapril might be advisable in severe renal impairment. 5. However, the majority of parameters of ACE inhibition were unrelated to creatinine clearance, although area under the curve for ACE inhibition (0-336 h) showed a weak negative correlation (r = -0.49, P < 0.01). Similarly, weighted mean changes in blood pressure were not influenced by renal function. 6. Therefore, while the pharmacokinetic parameters of trandolaprilat correlated with creatinine clearance, pharmacodynamic measurements (ACE inhibition and blood pressure changes) in general showed no such relationship, indicating that dose adjustment of ACE inhibitors in renal impairment should be based on pharmacokinetic results only in conjunction with pharmacodynamic data. PMID- 8443031 TI - The bioavailability of digoxin from three oral formulations measured by a specific h.p.l.c. assay. AB - 1. We have studied the absolute bioavailability of three oral formulations of digoxin, 1.0 mg, in 12 young healthy volunteers in a four way randomised cross over study using an intravenous control. 2. Digoxin tablets (250 micrograms), liquid filled digoxin capsules (100 micrograms) and an experimental enteric coated capsule (100 micrograms) were evaluated. In vitro dissolution at pH 1 demonstrated extensive hydrolytic breakdown of digoxin from the tablets and capsules but not from the enteric-coated capsules. 3. Serum 'digoxin' concentrations were measured by fluorescence polarization immunoassay (FPI). The systemic availability (+/- s.d.) of the capsules was 70.5 +/- 11.3%, and that of the tablets 71.5 +/- 8.6%. Drug was less available from the enteric-coated capsules (62.1 +/- 10.3%) measured with FPI. These results were reflected in the urinary drug recoveries measured by FPI. 4. By contrast, there were no differences in urinary recovery of unchanged digoxin between any of the oral treatments, when this was measured by h.p.l.c. The cross-reactivity of immunoassays for metabolites of digoxin may produce artefactual results and the optimal pharmaceutical formulation for digoxin remains to be determined. PMID- 8443032 TI - Effects of an oral dose of isosorbide dinitrate on platelet function and fibrinolysis in healthy volunteers. AB - 1. A randomised double-blind placebo-controlled study was performed to investigate the effects of isosorbide dinitrate (ISDN; 20 mg orally) on various aspects of platelet function and fibrinolysis in vivo in 12 healthy volunteers. 2. Measurements were performed at rest (before and after tablet ingestion) and during platelet activation by adrenaline (0.4 nmol kg-1 min-1; 30 min infusion). 3. At rest, ISDN did not alter plasma concentrations of beta-thromboglobulin (beta TG). EC50 values for ADP induced aggregation in vitro (Born aggregometry) or ex vivo filtragometry readings. Adrenaline markedly increased platelet aggregability in vivo as measured by filtragometry and elevated levels of beta TG in plasma. ISDN treatment did not affect these responses in the group as a whole. 4. Individuals responding to ISDN with more pronounced vasodilatation at rest showed a lesser increase in aggregability during the ensuing adrenaline infusion (r = -0.66, P = 0.02) despite higher adrenaline levels during ISDN. In individuals showing a significant decrease in systolic blood pressure (n = 8) ISDN tended to attenuate the adrenaline induced increase in platelet aggregability (filtragometry; P = 0.08), despite higher plasma adrenaline and noradrenaline levels after ISDN ingestion. 5. Plasma concentrations of ISDN and its active metabolites isosorbide-5-mononitrate and isosorbide-2-mononitrate were not correlated to haemodynamic or platelet variables. 6. Fibrinolytic activity (t PA antigen and activity, PAI-1 antigen and activity) increased similarly during the adrenaline infusion following ISDN and placebo. 7. It is concluded that ISDN may affect platelet aggregation responses to adrenaline in vivo, but only in individuals showing significant haemodynamic responses to ISDN.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8443033 TI - Patient knowledge about diuretic prescription. AB - 1. In order to assess the prevalence and knowledge of diuretic prescription, 203 consecutive admissions to three general medical wards were interviewed. Additional information was collected on forms sent to general practitioners and hospital doctors responsible for each patient. 2. Prevalence of diuretic use was 31% (63 patients); other drugs only, 60% (121 patients); no drugs, 9% (19 patients). Patients gave an incorrect indication for 31% of diuretics prescribed, but for only 16% of other drugs (P < 0.005). 3. Compared with patients not taking diuretics, diuretic-users were older (mean +/- s.d., 70 years +/- 14 vs 54 +/- 20, P < 0.001), had lower abbreviated mental test scores (AMT scores seven or less, 21% vs 9%, chi 2 = 3.48, P = 0.06) and were prescribed more drugs (5.0 +/- 2.4 vs 3.2 +/- 2.0, P < 0.001). Increasing age and decreasing AMT score were associated with poorer knowledge of drug indication, but these factors could not explain fully the poor understanding of diuretic prescription. 4. Accurate recall of dose was the same for diuretics and for other agents. Knowledge about medication was not different if the general practitioner or hospital initiated treatment. PMID- 8443034 TI - A study of the interaction between omeprazole and cyclosporine in renal transplant patients. AB - 1. To determine any interaction between omeprazole and cyclosporine A (CsA) 10 male patients with 1-7 year renal transplants and stable renal function, participated in this randomised blind cross-over trial with omeprazole, 20 mg, and placebo treatment once daily for 2 consecutive weeks each. 2. Blood samples for measurement of trough concentrations of CsA were obtained twice a week during the 4 study weeks, and during the 2 weeks before and after the study. Unchanged CsA concentrations were measured by h.p.l.c. and using a monoclonal antibody r.i.a., and drug plus metabolites were measured by a polyclonal antibody f.p.i.a. In addition, one of the metabolites, M17, was assayed separately by h.p.l.c. 3. The mean whole blood trough CsA concentration during omeprazole treatment was 102 (95% confidence interval, 84-122) micrograms l-1 determined by h.p.l.c. and 81 (65-100) micrograms l-1 determined by r.i.a. Corresponding values during placebo treatment were 100 (79-127) micrograms l-1 and 95 (75-120) micrograms l-1. The ratios between omeprazole and placebo treatments were 1.01 (0.84-1.22) (h.p.l.c.) and 0.85 (0.67-1.08) (r.i.a.). Assuming that a change of < 30% in CsA blood concentrations is of no clinical significance, these results show that there was no clinically or statistically significant influence of omeprazole on CsA concentrations. Neither CsA concentrations determined by f.p.i.a. nor determination of M17 by h.p.l.c. indicated any effect of omeprazole on the metabolism of CsA. 4. It is concluded that omeprazole (20 mg daily) does not significantly interfere with CsA metabolism in stabilised renal transplant patients and may be used safely without extra monitoring of blood CsA concentrations. PMID- 8443035 TI - Plasma concentrations and urinary excretion of histamine after inhalation and subcutaneous injection of histamine. AB - 1. Increased histamine concentrations are found in the plasma and urine following allergen challenge in allergic subjects. This study compared a controlled challenge with clinically relevant doses of inhaled and injected histamine, as indicative of an allergic response, in an attempt to validate the use of urinary histamine or 1-methylhistamine measurements as an objective, non-invasive diagnostic test. 2. Inhalation of histamine produced peripheral vasodilation, increased heart rate, a fall in partial expiratory flow rate (pEFR) and blood pressure, 'tight chest' and cough. Subcutaneous injection produced vasodilation and headache but no change in heart rate or blood pressure. 3. Plasma histamine concentrations were similar in the two studies. Inhalation of increasing doses of histamine through a nebuliser (output 0.13 ml min-1) resulted in an increase from a mean of 0.30 to 1.65 ng ml-1, with return towards baseline within 20 min. Injection of 1 mg histamine s.c. produced an increase from 0.32 to 1.4 ng ml-1 within 5 min, remaining above 1 ng ml-1 for 30 min. 4. There was a significant increase of 15.2 ng mg-1 creatinine in urinary histamine concentration following the injection of histamine (P = 0.04) and an increase of 11.4 ng mg-1 creatinine when histamine was given by inhalation (P = 0.18). Histamine excretion rate increased by 108 ng min-1 (P = 0.04) after inhalation and by 37.2 ng min-1 (P = 0.09) after injection. Urinary 1-methylhistamine concentrations were significantly raised following both histamine inhalation (+ 238 ng mg-1 creatinine; P = 0.013) and injection (+ 180 ng mg-1 creatinine; P = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8443036 TI - Capsaicin-desensitization to the human nasal mucosa selectively reduces pain evoked by citric acid. AB - 1. Kallidin (5-500 nmol), hypertonic saline (0.9-20% NaCl) or low pH medium (citric acid: pH 2.5-1) applied (50 microliters) to the human nasal mucosa produced a pain response (evaluated by a visual analogue scale) that was related to the concentration of the peptide, NaCl or hydrogen ions, respectively. 2. Application (50 microliters) of capsaicin (50 nmol) to the human nasal mucosa produced overt pain. After repeated administrations (once a day for 5-7 days) to one nostril this effect underwent almost complete desensitization, while in the contralateral nostril, treated with the vehicle, the response to capsaicin was unaffected. 3. The pain response produced in the human nasal mucosa by topical application (50 microliters) or kallidin (50-500 nmol), NaCl (10-20%) or citric acid (pH 1.5-1) solutions was then studied before and after local capsaicin desensitization. 4. The pain response to pH 1.5 or 1 citric acid was markedly reduced (by 60% and 75%, respectively) in the capsaicin-treated nostril. However, the pain response to 10% or 20% NaCl or the mild pain response to 50 or 500 nmol kallidin were unaffected by capsaicin pre-treatment. 5. The present results suggest that prolonged topical capsaicin treatment to the human nasal mucosa may lead to selective desensitization to certain algesic stimuli such as capsaicin itself and hydrogen ions. PMID- 8443037 TI - Modulation of capsaicin induced airway reflexes in humans: effect of monoamine oxidase inhibition. AB - 1. In animal studies monoamine oxidase (MAO) inhibition has been shown to reduce the cough response through elevation of 5-HT in the central nervous system. In this study the effect of selective inhibition of the two subtypes of MAO (MAO-A and MAO-B) was studied on human airway reflexes. 2. Capsaicin-induced cough and reflex increase in respiratory resistance were measured in nine normal volunteers before and after MDL 72394 (MAO-A inhibitor) 16 mg or MDL 72974A (MAO-B inhibitor) 12 mg. 3. Neither inhibitor altered capsaicin-induced cough. Following treatment with MDL 72394, however, the capsaicin-induced reflex increase in resistance was enhanced, by 5.97 +/- 2.1 fold of the placebo value at 1 h. 4. Thus, neurotransmitters in the central nervous system which are substrate for MAO A (i.e. noradrenaline, 5-HT) may be involved in the control of capsaicin-induced reflex bronchoconstriction. PMID- 8443038 TI - Assessment of the precorneal residence of an ophthalmic ointment in healthy subjects. AB - 1. The precorneal residence of an ophthalmic ointment radiolabelled by inclusion of technetium-99m tin colloid was assessed in seven volunteer subjects using the technique of gamma scintigraphy and compared with a solution of 0.3% w/v hydroxypropylmethylcellulose, (HPMC) radiolabelled by inclusion of technetium-99m diethylenetriaminepentaacetic acid in the same subjects. 2. The mean half-times (+/- s.d.) of corneal residence were 6490 +/- 5404 s (108 min) for the ointment and 13 +/- 24 s for the 0.3% w/v HPMC solution (P < 0.01). 3. The area-under curve value (AUC(0,540 s)), which reflects the total residence time of the preparation on the ocular surface, was calculated for each vehicle in each subject. The mean (+/- s.d.) AUC(0,540 s) value for the ointment was 42170 (+/- 5032)% s and for the 0.3% w/v HPMC solution it was 8394 (+/- 4641)% s (P < 0.01). PMID- 8443039 TI - Interactions among primaquine, malaria infection and other antimalarials in Thai subjects. AB - 1. The pharmacokinetics of rac-primaquine (45 mg base) and its principal plasma metabolite, carboxyprimaquine have been investigated in healthy Thai adults prior to and following a single oral dose of mefloquine (10 mg kg-1). 2. Primaquine was rapidly absorbed, attaining peak plasma concentrations (median and range) of 167 (113-532) micrograms l-1 in 2 (1-4) h. Thereafter, concentrations declined rapidly with an apparent terminal half-life of 6.1 (1.7-16.1) h and an oral clearance (CLpo) of 33.1 (17.6-49.3) l h-1. Administration of mefloquine had no effect on the values of any of these parameters at the 5% level of significance [Cmax 229 (114-503) micrograms l-1; tmax 3 (2-4) h; t1/2,z 3.9 (1.7-13.5) h; CLpo 34.0 (21.7-49.0) l h-1]. 3. The carboxylic acid metabolite of primaquine achieved maximum concentrations (median and range) of 890 (553-3634) micrograms l-1 at 6 (3-16) h. Thereafter, plasma concentrations of carboxyprimaquine declined to 346 (99-918) micrograms l-1 at 24 h. AUC (0,24 h) was 12737 (6837-27388) micrograms l 1 h. Administration of mefloquine had no effect on the plasma concentrations of this metabolite [Cmax 1035 (174-3015) micrograms l-1; tmax 8 (2-24) h; AUC(0,24) 13471 (2132-17863) micrograms l-1 h]. 4. The effect of falciparum malaria and treatment with quinine (10 mg salt kg-1 p.o.) on the pharmacokinetics of primaquine (45 mg base p.o.) has been investigated in adult Thai patients during and after infection with falciparum malaria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8443040 TI - Patients' attitudes to participation in clinical trials. AB - 1. In order to assess attitudes of patients to participation in therapeutic trials 197 patients underwent structured interviews conducted by a single observer. Of these patients 66 were previous or current participants in clinical trials (group A), 12 had declined participation in a trial (group B), and 119 had never been invited to participate in research (group C). 2. In group A, 62% stated their motivation for participation was to help others and 39% to improve their own treatment, but in 38% participation was to comply with the doctor's request. Two-thirds of group C patients would or might participate in a future hypothetical trial; of these more than half (57%) would do so to help others, and 42% to improve their own treatment. 3. Of the 12 patients who had declined entry into a study (group B) three did not want to alter their current therapy, three had insufficient time to participate in the particular trial, and in three cases relatives objected to their participation. Group C patients who stated they would not participate in trials gave being too ill (22%), not wanting to change treatment (22%), and fear of side-effects (17%) as the commonest reasons for declining. 4. In group A, 83% felt they had adequate time to consider their participation. Nearly two-thirds of patients (60%) would have liked written information to retain for reference, whereas only 38% were provided with information in this form. Over half of these patients (54%) disliked no aspect of the study in which they participated. Venepuncture and other uncomfortable procedures were least popular.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8443042 TI - Cytogenetic abnormalities in childhood acute lymphoblastic leukemias. PMID- 8443043 TI - Gastric perforation in non-Hodgkin's lymphoma. PMID- 8443044 TI - Successful use of partial splenic embolization in an infant with autoimmune hemolytic anemia. PMID- 8443041 TI - Treatment of vasculitis. PMID- 8443045 TI - Central nervous system disease in acute lymphoblastic leukemia. PMID- 8443046 TI - Post-monilial extensive esophageal stricture. PMID- 8443047 TI - Thalassemia: lung function with reference to iron studies and reactive oxidant status. AB - Pulmonary function tests were performed in 15 thalassemic patients (age 5 years 8 months to 18 years 6 months), receiving both regular transfusions and desferrioxamine, to determine the presence and nature of any abnormalities in lung function. Reactive oxidant production from neutrophils was measured simultaneously to ascertain if a causal relationship existed between free radical production and tissue damage in the lungs. Mean total lung capacity, mean residual volume, and mean forced vital capacity were significantly reduced, indicating a restrictive pattern of lung function abnormality. In addition, the carbon monoxide diffusion was low, and hypoxemia was present in 6 of 13 patients tested. These pulmonary function abnormalities did not correlate with age, cumulative volume of transfusion, or serum ferritin levels. In addition, neutrophil reactive oxidant status did not correlate with these or with pulmonary function parameters. These results indicate that neutrophil-derived oxygen free radicals do not appear to be a major cause of lung function abnormalities in thalassemics. PMID- 8443048 TI - Cytogenetic abnormalities in childhood acute lymphoblastic leukemia. AB - A review of the cytogenetic analyses of a cohort of unselected patients with acute lymphoblastic leukemia from a single institution (1981-1989) confirmed hyperdiploidy > 50 as a favorable prognostic feature and pseudodiploidy, especially with chromosomal rearrangements, as an adverse one. In the early years of the study, a high incidence of diploid karyotype was identified, but with time (better banding and more intensive search) the incidence has fallen to 7.7%. Many such patients have been shown to be pseudodiploid. Molecular genetic techniques are increasingly identifying clonal abnormalities. PMID- 8443049 TI - Growth hormone and leukemia. PMID- 8443051 TI - Reversible cardiopathy after accidental overdose of mitoxantrone. AB - Mitoxantrone is an anthraquinone structurally related to the anthracycline drugs doxorubicin and daunorubicin. In animal tumor models, it was equally cytotoxic as but less cardiotoxic than the parent compounds. We here describe the clinical course of a 9-year old girl who inadvertently received 100 mg/m2 of mitoxantrone as a bolus injection. Hemoperfusion carried out twice with the objective of increasing the drug clearance was totally inefficient. Severe but transient myelotoxicity was induced. Sequential echocardiograms demonstrated a reversible decrease of the shortening fraction of the left ventricle. PMID- 8443050 TI - MYCN amplification by differential PCR. AB - A method is described to estimate MYCN (N-myc) oncogene amplification in neuroblastoma by the technique of differential polymerase chain reaction (PCR). The technique is quicker than conventional Southern blotting techniques and does not require radioactive materials. The ability to measure MYCN amplification from smaller amounts of tumor DNA also permits measurement from Tru-cut biopsy samples and opens the possibility of retrospective measurement of MYCN status from single paraffin sections of archival material. PMID- 8443052 TI - Growth hormone treatment and development of malignancy: recombinant human growth hormone does not induce leukemia in AKR/O-mice. AB - In 1988 several reports described leukemia in former/present growth hormone (GH) treated children, and a doubled incidence of leukemia in GH-treated children was concluded in a workshop in Bethesda. A mouse strain (AKR/O) with a high incidence of leukemia was used as a model. AKR/O-mice in the preleukemic adult age and younger mice during rapid growth were treated with recombinant human GH (rhGH) in human therapeutic doses to see whether this treatment would affect the time and presentation of malignant disease. The malignant development did not appear earlier or in a different way in the animals receiving rhGH from day 6 to 50 than in their appropriate controls. A borderline protective effect to the development of leukemia was seen in the adult group receiving rhGH; in this group antibodies to hGH also developed. We conclude that in this experimental model human therapeutic doses of rhGH do not influence the development of malignancy in the AKR/O mice. PMID- 8443053 TI - Late leukemic relapse 10 years from diagnosis in a child on recombinant human growth hormone. AB - A 12 year-old girl developed a late relapse of acute lymphoblastic leukaemia (ALL) 10 years from first presentation. Initial chemotherapy included vincristine, methotrexate, prednisolone, and L-asparaginase with cranial radiotherapy (18 Gy) for central nervous system prophylaxis. Documented growth failure led to recombinant human growth hormone (rhGH) replacement therapy being instituted in May 1989, 6 years from end of therapy and 2 years prior to relapse. Three independent experiments demonstrated no increased cell proliferation in vitro when the patient's thawed cryopreserved fresh leukemic cells were incubated with rhGH. However, a pre-T ALL cell line (PER-255) consistently demonstrated enhanced proliferation when incubated with rhGH (132.1 +/- 13.4%, P < 0.01). Growth hormone has been associated with an increased incidence of leukemia and may be implicated in the late relapse of this child. The use of growth hormone in children with a past history of ALL needs to be examined critically in the light of the potential risk of inducing leukemic relapse. PMID- 8443054 TI - Report on the international workshop of the Kind Philipp Foundation on late effects after bone marrow transplantation in childhood malignancies. AB - This report is a short summary of an international workshop on late effects after bone marrow transplantation in pediatric patients. Main topics of the report are chronic GVHD and immune reconstitution and the late effects of this kind of treatment on growth, respiratory function, the endocrinological system, teeth, and eyes. The development of secondary tumors is discussed as well as the influences on the central nervous system and behavior of children. PMID- 8443055 TI - Constitutive heterochromatin polymorphisms in children with acute lymphoblastic leukemia. AB - The C-band heterochromatin polymorphisms of chromosomes 1, 9, and 16 were studied on peripheral lymphocytes of 67 children with acute lymphoblastic leukemia (ALL) and 50 control individuals. A statistically significant difference between patients and controls was found for large heterochromatin regions (level 3) of chromosomes 1 and 9 (P < 0.001) and for small heterochromatin regions (level 1) of chromosome 16 (P < 0.001). The patients also showed a significant increase in chromosomes 1 and 9 heteromorphism with respect to controls (P < 0.001). PMID- 8443057 TI - Long-term prednisolone therapy in children with idiopathic pulmonary hemosiderosis. PMID- 8443056 TI - Cutaneous relapse in a child with acute mixed leukemia. PMID- 8443058 TI - Tuberculosis. Secular trends of tuberculosis in Western Europe. PMID- 8443059 TI - Asthma. 1980-1990. PMID- 8443060 TI - Dracunculiasis. Update, 1992. PMID- 8443061 TI - Expanded programme on immunization. Immunization coverage survey by telephone. PMID- 8443062 TI - Cardiovascular diseases. Trends in ischaemic heart disease mortality, 1980-1988. PMID- 8443063 TI - Influenza. PMID- 8443064 TI - Pamphlet AIDS/HIV advice is not sufficient. PMID- 8443065 TI - Pre-ejaculatory fluid risk for HIV spread. PMID- 8443066 TI - Human rights: taking urgent action. PMID- 8443067 TI - Skill mix: quality of care or quality of service? PMID- 8443068 TI - Decubitus ulcers: a multidisciplinary view. PMID- 8443069 TI - Empowering nurses in the health service. PMID- 8443070 TI - The use of drama in health education. AB - The focus of Project 2000 courses has been on the development of a health rather than sickness concept throughout the curriculum. Such a fundamental change in emphasis requires, it is argued, a different concept of the preparation of students in appropriate attitudes, skills and knowledge. The author describes an innovative approach to education that uses drama to improve communication skills in a group of nursing students. PMID- 8443071 TI - Mental Health Act: detention in A & E. AB - Meeting the needs of clients with mental health problems in the accident and emergency (A&E) department requires all members of the multidisciplinary team to be familiar with the Mental Health Act (1, 2). In particular, nurses registered on parts 3, 5, 13 and 14 of the Professional Register (3) and working in A&E should be aware of section 5 (4), the nurse's six-hour holding power (1) and its equivalent, section 25 (2) of the 1984 Mental Health (Scotland) Act (2), and the possible implications of their use in practice. PMID- 8443072 TI - Telephone triage: extending practice. PMID- 8443074 TI - Information technology: its bark is worse than its byte. PMID- 8443073 TI - Controlling emesis after chemotherapy. PMID- 8443075 TI - Back to the future: New Year's revolution. PMID- 8443076 TI - HIV/AIDS education: philately will get you everywhere. PMID- 8443077 TI - Older, wiser (and threatened). PMID- 8443078 TI - Nurse, get on the scrap heap. PMID- 8443079 TI - The Sister Susie column. Justifying an unqualified success? PMID- 8443080 TI - Barrier contraception: issues and trends (continuing education credit). PMID- 8443081 TI - HIV and AIDS: a positive response (continuing education credit). PMID- 8443082 TI - Elderly care: a poor substitute for life. PMID- 8443083 TI - Childbearing within the prison system. AB - The immediate pre and postnatal periods are a time of high anxiety for most women, but for those living in prisons, the stressors can be multiplied. Deprived social backgrounds, inconsistent family contact, isolation, poor physical and mental health, and the probability that the baby will be put into care are some of the problems such women face. This article describes the provision of health care generally for women in prison, then examines the particular problems faced by those who are pregnant. PMID- 8443084 TI - Lying to patients: can it ever be justified? AB - The acts of withholding information from patients and of deliberately issuing false information have been embodied in nursing and medical practice for centuries. The author considers the relationship of veracity, or truth-telling, to the four established tenets of medical ethics: autonomy, justice, beneficence and non-maleficence. Although there are occasions when withholding information can be supported, particularly when the patient has requested that this be so, she concludes that there can be no moral justification for health professionals lying to patients. PMID- 8443085 TI - Gastric lavage in accident and emergency. AB - There are few specific treatments available to neutralise the effect of ingested toxic agents. For most overdose patients presenting to accident and emergency (A&E) departments, therefore, the aim of treatment is to limit the systemic absorption of the drug or drugs taken. Gastric lavage is a traditional intervention for managing overdose patients in A&E and the author outline how this procedure may be performed. PMID- 8443086 TI - Mental health: an outreach service for adolescents. AB - In 'The Health of the Nation' (1), the government committed itself to seeking continued improvements in comprehensive local services for mental illness not only in adults, but also in children and adolescents. The adolescent unit outreach service described in this article offers an intensive therapeutic and consultative service for disturbed young people. The aim is to maximise the opportunities for care in the community and thus reduce the need for inpatient admissions. The authors discuss the early developments of an outreach service and identify appropriate research questions. Application for funding to help evaluate the service is currently under way. PMID- 8443087 TI - Community care: home sweet home? PMID- 8443088 TI - Community care: powerless to be empowered. PMID- 8443089 TI - Computers: shopping for systems. PMID- 8443090 TI - Cardiology update. The sound revolution. PMID- 8443092 TI - Depression: lifting the cloud (continuing education credit). PMID- 8443091 TI - Cardiology update. Modern management of cardiac failure. PMID- 8443093 TI - Suicide: a target for health (continuing education credit). PMID- 8443094 TI - An approach to the management of arrested and compensated hydrocephalus. AB - Arrested hydrocephalus is defined as adequately shunted hydrocephalus while all other forms of hydrocephalus are at various levels of compensation. Compensation occurs at some cost to the child. Weighing the cost of compensation versus the risk of a shunt is used to decide which course to follow. Close observation with objective data is mandatory if the decision is made not to shunt the young child. In the very young, less than 3 years of age, one should probably err on the side of inserting a shunt. PMID- 8443095 TI - Physician-patient-parent communication problems. AB - The physician-patient relationship has been addressed frequently in the literature. It is well documented that a positive physician-patient relationship is influential in clinical outcome. This concept is even more complex in pediatrics (and pediatric neurosurgery) where the physician must 'relate' or 'communicate' with the entire family. Complications in physician-parent-child communication occur for a variety of reasons. Most commonly, they occur as a result of lack of communication, miscommunication and/or information overload. The intent of this paper is to discuss the pediatric neurosurgeon-parent-child communication complications and to identify strategies for their prevention. PMID- 8443096 TI - Peritoneal catheter insertion using laparoscopic guidance. AB - The use of laparoscopic guidance for abdominal puncture and introduction of ventriculoperitoneal shunt peritoneal catheters using a peritoneal split trocar is proposed. The technique permits location of the catheter in the right parietocolic space or its relocation if trapped within the omentum. Cerebrospinal fluid flow is certified. Since the submission of the paper 6 selected cases have been operated upon without complications. PMID- 8443097 TI - Problems in the nosology of desmoplastic tumors of childhood. AB - Several types of central nervous system tumors primarily consisting of a combination of astrocytes and fibrocollagen and occurring most commonly in infancy have been separately introduced as new diagnostic entities. The names applied to these tumors have included 'gliofibroma', 'desmoplastic cerebral astrocytoma', and 'desmoplastic infantile ganglioglioma', a group containing ganglion cells as well as the astrocytes and mesenchymal tissue. We studied a gliofibroma arising in the fourth ventricle of a 6-month-old infant and three examples of desmoplastic cerebral astrocytoma in infants utilizing routine histological and immunocytochemical methods, and at the ultrastructural level in two tumors. In view that the desmoplastic cerebral astrocytomas contain poorly differentiated neuroepithelial cells and rarely, a ganglion cell, we suggest that gliofibroma and desmoplastic astrocytoma are basically the same entity and that the desmoplastic infantile ganglioglioma is a variant containing primitive or mature ganglion cells. PMID- 8443098 TI - Total cranial vault reconstruction for the older child with scaphocephaly. AB - A technique is described for the surgical correction of primary of secondary sagittal synostosis in the older child. This involves placing the patient in the modified prone position, reshaping the supraorbital bar, and reconstructing virtually the entire cranial vault with microplates. This technique of total cranial vault reconstruction has been performed successfully on 5 patients without mortality or significant morbidity, although blood loss is significant, averaging 1.8 blood volumes. Further experience will be needed to establish the proper indications for the procedure, the best method of fixation, and the optimal timing. PMID- 8443099 TI - Significance of the lateral canthal tendon in craniofacial surgery. AB - Craniofacial approaches to the anterior skull base involve manipulation or removal of the supraorbital and frontozygomatic orbital margins. Necessarily, structures within the orbit are detached from the orbital margins. The lateral canthal tendon is attached to the inner aspect of the frontozygomatic process on the orbital osseous tubercle and is essential to the structural fixation of the lateral canthus as well as a check on the mobility of the lateral canthal angle of the eye itself. Our anatomic studies on the lateral canthal tendon as well as specific neurosurgical considerations in its mobilization are reviewed. The detachment of the lateral canthal tendon may result in blunting of the lateral canthal angle, a distraction of the eyelid away from the globe, or an asymmetric repositioning of the canthus as compared with the contralateral angle. It would appear that if the periosteum of the orbit is carefully dissected from the orbital rim and reapproximated following the procedure, the lateral canthal tendon insertion and function will not be disturbed unless the bony orbit margins are altered. In these instances, further ocular plastic surgery may be required. PMID- 8443100 TI - Multiple epidural hematomas following ventriculoperitoneal shunt. AB - Although extra-axial hematomas are a well-known complication of ventricular shunting, epidural hematomas are uncommon in this setting. We report an unusual case of multiple epidural hematomas in a patient with hydrocephalus treated by ventriculoperitoneal shunt. The patient became symptomatic 5 days after shunting and required craniotomy for evacuation of one of the hematomas. The literature is reviewed and treatment discussed. PMID- 8443101 TI - Dermoid in the filum terminale of a newborn with myelomeningocele. AB - Delayed occurrence of dermoid and epidermoid tumors after myelomeningocele closure has been reported in 16% of patients. Inclusion of cutaneous remnants at the time of surgical closure of the myelomeningocele has been accepted as the most common cause for the development of these intraspinal lesions. The finding of dermal elements (congenital dermoid) within the filum terminale of a newborn with myelomeningocele offers evidence of another mechanism for the delayed occurrence of these tumors in patients with myelomeningocele. PMID- 8443102 TI - Scalp hamartoma in identical twins. AB - Identical twin male infants had scalp hamartomas removed from the occipital region. The histologic features and genetic implications of these unusual lesions are discussed. PMID- 8443103 TI - Muscle weakness in a 16-year-old girl. PMID- 8443104 TI - Analyses of the Drosophila quit, ovarian tumor and shut down mutants in oocyte differentiation using in situ hybridisation. AB - We have studied the role of three loci, quit, ovarian tumor and shut down during oocyte differentiation in Drosophila by using in situ hybridisation and double mutant analyses. Mutations in qui and otu disturb the cystocyte divisions and the oocyte determination, while mutations in shu affect the cystocyte integrity, nevertheless allowing differentiation of normal-looking egg chambers with an oocyte. In all mutants the transport of molecules towards the posterior end of the egg chamber takes place as revealed by the accumulation of Bic-D or K10 transcripts. We show that the transport is ineffective in the qui and otu mutants apparently due to the lack of a properly differentiated oocyte. In the shu mutant the transport collapses and the oocyte is lost, leading to egg chambers with 15 nurse cells. We also show that one function of qui+ is to enhance otu+ mRNA expression, suggesting that these genes control the cystocyte maturation via the same pathway. PMID- 8443105 TI - XASH1, a Xenopus homolog of achaete-scute: a proneural gene in anterior regions of the vertebrate CNS. AB - The pro-neural achaete-scute complex (ASC) of Drosophila encodes four homologous proteins, each containing a basic helix-loop-helix (bHLH) domain, characteristic of a large family of transcription factors. We have isolated XASH1, a Xenopus homolog of achaete-scute. The XASH1 protein is very similar to the ASC proteins of Drosophila and the rat homolog, MASH1. XASH1 is expressed in the embryonic anterior central nervous system in a dynamic sequence, first in the midbrain, then in the forebrain, and then in the eye and hindbrain. In the larva, XASH1 expression correlates with regions of continued neurogenesis in the CNS, revealing the pattern of rhombomeres in the hindbrain, and other proliferative zones in the eye and midbrain. As a heterodimer with the bHLH protein E12, XASH1 binds specifically to an enhancer sequence derived from the promoter of the proneural achaete gene of Drosophila. This binding is inhibited by the extramacrochaete protein, a negative regulator of ASC gene function and neurogenesis in Drosophila. The combined evidence described in this paper strongly suggests that XASH1 plays a role in Xenopus neurogenesis similar to that played by the ASC genes in Drosophila. PMID- 8443106 TI - Control of tailless expression by bicoid, dorsal and synergistically interacting terminal system regulatory elements. AB - Three different maternal morphogen gradients regulate expression of the gap gene tailless (tll), which is required to establish the acron and telson of the Drosophila embryo. To identify elements in the tll promoter that respond to these different maternal systems, we have generated promoter-lacZ fusions and transformed them into the germline. Expression of these constructs in both wild type and mutant embryos revealed the presence of at least two separate but synergistically interacting regions that mediate tll expression by the terminal system. This functional synergism between regulatory elements may play a role in the translation of the torso (tor) morphogen gradient into the sharp boundary of tll gene activity. In addition to regions mediating activation by the terminal system, regions mediating both activation and repression by bicoid (bcd), and repression by dorsal (dl) were identified. Binding sites of bcd protein in a 0.5 kb region, revealed by DNaseI footprinting, could be crucial for the bcd dependent activation of tll expression in the anterior stripe. PMID- 8443107 TI - Isolation of cDNAs for two closely related members of the axolotl Wnt family, Awnt-5A and Awnt-5B, and analysis of their expression during development. AB - To characterize molecular interactions between cells in the early amphibian embryo, we have isolated cDNAs for two members of the axolotl (Ambystoma mexicanum) Wnt family, Awnt-5A and Awnt-5B. The encoded proteins share 83% amino acid identity. Using a reverse transcription-polymerase chain reaction (RT-PCR) assay, we find that Awnt-5A transcripts are abundant in the blastula until gastrulation, barely detectable during gastrulation, and increase again during neurulation. They are detected throughout the remaining development and in hatched larvae. In contrast, transcripts for Awnt-5B are undetectable in the blastula. They appear with gastrulation, are present throughout neurulation and organogenesis, and decrease to barely detectable levels in hatched larvae. PCR reactions performed using cDNA library-phage DNA templates derived from whole neurulae versus embryos with the neuroectoderm removed suggest that, in the neurula, Awnt-5A transcripts are present in neuroectodermal as well as non neuroectodermal tissues while Awnt-5B mRNAs are predominantly localized in the neuroectoderm. To localize Awnt-5A expression in embryos before gastrulation, early gastrulae were dissected by cutting along the animal-vegetal and future dorso-ventral axes and analyzed by RT-PCR. At this early stage, Awnt-5A transcripts appear to be predominantly localized in the dorso-vegetal region of the embryo. These results suggest that the two closely related Awnt-5 genes participate in different morphogenetic processes during early axolotl development. PMID- 8443108 TI - The structure and expression of the Xenopus Krox-20 gene: conserved and divergent patterns of expression in rhombomeres and neural crest. AB - Recent studies in the chick have indicated that rhombomeres (r) are segments that underlie the patterning of hindbrain nerves. These segments may also be important for the specification of branchial arch structures since alternating rhombomeres, r2, r4 and r6, each contribute crest to a specific arch. Krox-20 has been implicated in the segmental patterning of the hindbrain in the mouse by its expression prior to segment formation in alternating domains, which later correspond to r3 and r5. Here, we describe the sequence and developmental expression of the Xenopus Krox-20 gene, XKrox-20. Alternating domains of XKrox-20 expression appear in the early neurula, later correspond to r3 and r5, and persist until late tadpole stages. In contrast to this conserved spatial expression in rhombomeres, we find a pattern in the neural crest of Xenopus that appears different from that found in the mouse: expression occurs in crest that migrates from r5 into the third visceral arch. We speculate that this may reflect a distinct route of neural crest migration due to anatomical differences between these systems, rather than a difference in the site of origin of Krox-20 expressing crest. PMID- 8443109 TI - Levator aponeurosis elastic fiber network. AB - This light and electron microscopic study demonstrates an elastic fiber network (EFN) for the levator palpebrae superioris muscle complex, which forms an intricate insertion into the upper eyelid. The EFN is examined in the monkey, in a fresh exenteration specimen, and in fresh frozen cadaver specimens from both sexes of different age groups. Multiple elastic insertions of the levator aponeurosis and Muller's muscle attachment with well-organized elastic fibers are demonstrated using special staining techniques and serial microscopic sectioning. Transmission electron microscopy (TEM) confirms the ultrastructure of "mature" elastin fibers in Muller's muscle tendon and their close relationship with the elastin-related fiber, oxytalan. Current thinking concerning the nature of elastic fibers and their possible implications in acquired involutional blepharoptosis is discussed. This microscopic study of the EFN of the upper eyelid focuses attention on the multiple elastic fiber insertions of the levator muscle complex that includes the levator aponeurosis, the conjoined fascia, the lid crease area, and Muller's muscle tendon, which have not been previously described. PMID- 8443110 TI - Acquired lacrimal drainage obstruction: an etiologic classification system, case reports, and a review of the literature. Part 3. PMID- 8443111 TI - Clinical study on the effectiveness of tear drainage with a single canalicular system under environmental stress. AB - Sixteen asymptomatic volunteers had their right lower puncta occluded with a Freeman silicone plug. They then went about their normal daily activities for approximately 1 week under the stress of a cold Chicago winter. Of the 16 eyes that were plugged, 4 had epiphora. The episodes were of short duration and did not have any effect on the subjects' daily activities. When comparing the incidence of epiphora between the plugged eyes and the control eyes, there was no statistically significant difference (p = 0.082). Also, when comparing the modified Jones I test and Schirmer tests, with and without anesthesia, there was no significant difference in the values between the plugged and the control eyes (p > 0.05). The only difference noted was in the dye disappearance test (p < 0.05). These results support the hypothesis that in selected patients, even under stressful environmental conditions, a single healthy canaliculus may provide sufficient tear drainage from a normal eye to prevent bothersome subjective symptoms. PMID- 8443112 TI - Silastic intubation in congenital nasolacrimal duct obstruction: a study of 129 eyes. AB - Congenital nasolacrimal duct (NLD) obstruction, the most common cause of congenital epiphora, occurs in approximately 5% of newborns. Before the advent of canaliculodacryo intubation, management of most cases of partial lacrimal obstruction that failed conservative management and probing necessitated bypass surgery such as dacryocystorhinostomy. Noninvasive closed system lacrimal intubation improved the success rate and provided a non-surgical therapeutic alternative. We present 129 eyes with congenital NLD obstruction managed with silastic lacrimal intubations. Early management is recommended with a minimum of 7 months' retention of the stents. Statistical assessment of results and management of complications is presented. PMID- 8443113 TI - Management of acute dacryocystitis in adults. AB - Acute dacryocystitis frequently is extremely painful and slow to resolve even with systemic antibiotic therapy. We have identified that incision, drainage, and direct application of antibiotics inside the infected sac result in almost immediate resolution of pain and rapid control of infection. This also provides optimal culture material. Twelve consecutive patients treated in this manner had rapid control of the acute infectious process. All eight patients subsequently undergoing dacryocystorhinostomy were fully cured. A total of 58.3% of the patients were infected with gram-negative rods; 50% of the isolates were resistant to most oral antibiotics. PMID- 8443114 TI - Lacrimal sac, conjunctival, and nasal culture results in dacryocystorhinostomy patients. AB - Chronic dacryocystitis is commonly seen in patients requiring a dacryocystorhinostomy (DCR). The infection may be primary, or may be secondary to an anatomical abnormality that has led to tear flow stasis. It is possible that many cases of primary acquired nasolacrimal duct obstruction are in fact secondary to unrecognized low-grade dacryocystitis. The intent of this study was to determine what organisms grow in the lacrimal sac of patients requiring DCR. It also investigated whether or not there was a correlation between organisms cultured from the sac and from the conjunctiva and/or the nose. The results of the study indicate that there is not a clinically significant correlation. The level of obstruction does not affect whether similar organisms were cultured from the three sites. PMID- 8443115 TI - Ocular motility disorders secondary to sinus surgery. AB - Sinus surgery has multiple potential ocular complications including visual loss, diplopia, infection, hemorrhage, and epiphora. We report six patients with ocular motility problems secondary to sinus surgery, review the literature on ocular motility disorders secondary to sinus surgery, and propose an approach for management of those ocular motility problems following sinus surgery. Intranasal sinus surgery was found to be the most common procedure resulting in injury to an extraocular muscle and the ethmoid sinus the most common structure being operated on when injury occurred. The medial rectus was the muscle most commonly injured and it had the poorest prognosis for recovery of functional vision free of diplopia. Optimal timing for repair depends on the structure injured, but early recognition and management appear to be a key to the best outcome for these injuries. PMID- 8443116 TI - Spontaneous direct carotid-cavernous fistula in childhood. AB - We report the occurrence, surgical treatment and long-term follow-up of a spontaneous, direct carotid-cavernous fistula in a child. It is the third angiographically documented, spontaneously occurring fistula to be reported in this age group and the first to arise directly from the internal carotid artery based on our review of the literature. Although our patient required fistula closure, other reported fistulae were nonprogressive and did not require treatment. The communication between the internal carotid artery and the cavernous sinus was left sided while the contralateral eye was proptotic. The clinical features, selected hemodynamic characteristics, and treatment of carotid cavernous fistulas are reviewed. PMID- 8443117 TI - Banked fascia lata as an orbital floor implant. AB - Synthetic orbital floor implants carry the risk of infection, rejection, anterior migration with prolapse, and posterior migration with optic nerve compression. Banked irradiated homologous fascia lata has been used as an orbital floor implant in the repair of 18 patients with surgically indicated orbital floor fractures. All patients had improvement in diplopia. There was no infection, anterior migration, or posterior migration of the implant. There was no reported transmission of communicable diseases. Early results suggest that banked irradiated fascia can be used effectively and safely as an orbital floor implant in selected cases. PMID- 8443118 TI - Orbital panniculitis as the initial manifestation of systemic lupus erythematosus. AB - Inflammation of the fat in lupus erythematosus also known as lupus erythematosus profundus (panniculitis) is a rare clinical entity. As the presenting feature of lupus, it is even more unusual. In this report, we describe an elderly woman who presented with an orbital mass infiltrate as the initial manifestation of lupus that had the classical histological features of lupus panniculitis. PMID- 8443119 TI - An analysis of idiotype expression in a high-affinity, somatically mutated variant of a germline-encoded anti-p-azobenzenearsonate antibody. AB - Using two polyclonal (rabbit) and two monoclonal anti-idiotype (anti-Id) reagents, we investigated structural correlates of the Id of mAb 36-71, a somatically mutated member of the CRIA Id family that has an exceptionally high affinity for the p-azobenzenearsonate (Ars) hapten. The two monoclonal anti-Ids reacted principally with the L chain of 36-71. The polyclonal anti-Ids interacted with both the H and L chain. The amino acid sequences of the VH and VL regions of 36-71 differ in eight and 11 positions respectively from those of the anti-Ars mAb 36-65, an unmutated prototype of the CRIA family. In the presence of 36-71L only three substitutions in 36-65 VH, introduced by mutagenesis, sufficed to restore full expression of the 36-71 Id. The same three substitutions had previously been shown to increase the affinity of 36-65 by a factor of 200, to a level equivalent to that of 36-71. X-ray crystallography had indicated that two of these substitutions introduce conformational changes consistent with the increase in affinity. We propose that these conformational changes may also account for the critical role of the three amino acids in Id expression. We also found that 36-65 is a very poor inhibitor of the interaction of 36-71 with its polyclonal anti-Ids, despite identity of the hapten-contacting residues in the two mAbs and evidence (from hapten inhibition) that the hapten-binding region is part of an important Id. Again, a difference in conformation at the binding site of the two mAbs could account for these observations. PMID- 8443120 TI - Self-restricted primary human histocompatibility leukocyte antigen (HLA)-specific cytotoxic T lymphocytes. AB - The specificity of self MHC-restricted T cells responding to peptide fragments of processed antigen has been well characterized. However, the means by which alloreactive T lymphocytes recognize MHC alloantigen remain poorly understood. We now provide evidence that the recognition of class I human leukocyte antigen (HLA) alloantigen by alloreactive cytotoxic T lymphocytes (CTL) induced in primary mixed lymphocyte cultures is class I HLA-restricted to a great extent. This is shown by the 'split-well' limiting dilution assay using third party target cells bearing a stimulating class I HLA alloantigen either in (i) the presence or (ii) the absence of class I HLA antigen(s) which is shared with the responder. Alloreactive CTL were found which recognize stimulator class I HLA alloantigen on the first but not on the second type of target cells. The results show that, in contrast to the traditional view, a large proportion of the alloreactive CTL against class I HLA alloantigen generated in primary mixed lymphocyte cultures is self class I HLA-restricted. PMID- 8443121 TI - Skewed T cell receptor V alpha repertoire among superantigen reactive murine T cells. AB - Reactivity of murine T cells with viral or bacterial superantigens is clearly correlated with the expression of TCR V beta domains. Thus, T cells responding to the minor lymphocyte stimulatory locus (Mls-1a) or staphylococcal enterotoxin B (SEB) express predominantly TCR V beta 6 or V beta 8.2 respectively. We have investigated the involvement of the other major variable element of the TCR, the V alpha domain, in these superantigen responses. Using a panel of anti-TCR V alpha mAbs, it is demonstrated that the TCR V alpha repertoire among superantigen stimulated V beta 6+ or V beta 8.2+ blasts (responding to Mls-1a or SEB respectively in vitro) is altered in comparison with anti-CD3 stimulated cells expressing the same V beta domains. Furthermore, the TCR V alpha repertoire is strongly skewed in TCR V beta 8.2 transgenic mice that have undergone extensive peripheral clonal deletion after SEB injection. These data imply that the V alpha domain influences superantigen recognition by the TCR. PMID- 8443123 TI - Resting B cells can act as antigen presenting cells in vivo and induce antibody responses. AB - Although it is well established that B lymphocytes are able to present antigen in vitro, the ability of small resting B cells to act as antigen presenting cells in vivo remains controversial. In this report we have studied the antigen presentation and the antibody response induced by mouse B cells after in vivo or in vitro targeting antigens to membrane Ig (mIg), using rat mAbs. Our results show that injection of these mAbs coupled to 2,4-dinitrophenyl (DNP) strongly enhances the IgG1 antibody response against DNP and rat Ig. T cell depleted spleen cells pulsed in vitro with rat Ig without specificity for B cells induced an antibody response when re-injected into mice, this response being much higher if the antigen was specific for mIg. Moreover, purified resting B cells were shown to induce a specific IgG1 response in vivo only when they were cultured with rat mAb against mIgM or mIgD but not with myeloma rat Ig of the same isotype. B cells do not need to be activated to present antigen since the induction of the specific antibody response does not correlate with the mitogenic activity of rat mAb nor with the IgG1 polyclonal synthesis in vivo. These data clearly show that resting B cells can present antigen in vivo and induce an antibody response, and underline the importance of mIgM and mIgD as targets for antigens. PMID- 8443122 TI - Expression of PILOT, a putative transcription factor, requires two signals and is cyclosporin A sensitive in T cells. AB - Few known genes (IL-2, members of the IL-8 family, interferon-gamma) are induced in T cells only through the combined effect of phorbol myristic acetate (PMA) and a Ca(2+)-ionophore, and expression of only these genes can be fully suppressed by Cyclosporin A (CyA). We have identified a putative transcription factor, designated PILOT, with an identical dual signal requirement for expression. Induction of the PILOT gene is detectable in human T cells 20 min following activation in the presence of cycloheximide and is fully suppressed by CyA. The PILOT protein has a calculated M(r) of 42.6 kDa and contains three zinc fingers of the C2H2-type at the carboxyl-terminus which are highly homologous to the zinc finger regions of the transcription factors EGR1, EGR2, and pAT 133. In contrast to T cells, in fibroblasts PILOT gene expression requires only one signal (PMA) and is not affected by CyA. This observation directly demonstrates the existence of a Ca2+ signal-dependent regulatory element obligatory for expression of some genes in T cells but not in fibroblasts. This differential expression model will be valuable in the dissection of the dual signal pathway in T cells and the effects of CyA upon it. PMID- 8443124 TI - A novel CD45RA+CD4+ transient thymic subpopulation in MRL-lpr/lpr mice: its relation to non-proliferating CD4-CD8-CD45RA+ tumor cells. AB - MRL-lpr/lpr mice have hypertrophied lymph nodes comprising CD4-CD8- T cells. In addition, they contain CD4+CD8- T cells co-expressing the CD45RA marker. The correlation between these two subpopulations has been difficult to assess. We analyzed the expression of CD45RA (with the RA3-2C2 antibody) in various thymic and peripheral T cell subsets, using three-color immunofluorescence. We showed that in lpr mice (i) a transient CD4+CD8- thymic subset co-expresses CD45RA during the course of the disease, and (ii) thymic as well as peripheral CD4-CD8- and CD4+CD8- T cells brightly express CD45RA; furthermore (iii) in the lymph nodes, during lymphadenopathy, CD4+CD8-CD45RA+ T cells show a broad range of the CD4 fluorescence intensity, and (iv) the increase in MHC class II expression is restricted to CD45RA-T cells of the thymus and lymph nodes of lpr mice. Taken together, these data suggest that the CD4+CD8-CD45RA+ population might generate the CD4-CD8- tumor cells. In addition, using the bromodeoxyuridine labeling technique, we demonstrate that these cells are not the result of increased proliferation. PMID- 8443125 TI - N-acetylcysteine enhances T cell functions and T cell growth in culture. AB - N-Acetylcysteine (NAC) is highly nontoxic for peripheral blood T cells and immunostimulatory enhancing T cell functions such as mitogenesis, interleukin-2 (IL-2) production, and growth in culture. NAC has been proposed for the treatment of AIDS based on its inhibition of human immunodeficiency virus (HIV) replication in cultured cells. Therefore its effect on normal T cells from 10 young donors and one elderly donor has been investigated as a prelude to clinical consideration. T cell function was evaluated in the presence and absence of accessory cells. With concanavalin A and anti-CD3 activation, NAC enhanced mitogenesis by approximately 2- to 2.5-fold at 5-10 mM. Mitogenesis of purified T cells with anti-CD2 was not affected by NAC; in the presence of accessory cells, NAC enhanced mitogenesis by approximately 2-fold at 1-10 mM. Importantly, NAC levels above 10 mM completely inhibited activation of peripheral blood mononuclear cells by anti-CD2. IL-2 secreted by T cells was also enhanced by NAC, approximately 1.5-fold, but IL-2 secreted by cells from old donors was enhanced by 3-fold. In cultures of peripheral blood T cells, NAC (10 mM) stimulated growth by at least 4- to 6-fold after two passages. These results show that NAC, nontoxic even at 20 mM, is an effective enhancer of T cell function and a remarkable enhancer of growth. Results from other laboratories show that NAC, which increases glutathione levels, suppresses HIV replication presumably via suppression of the activation of transcriptional factor NF-kappa B.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8443126 TI - Molecular modelling of the specific interactions involved in the amylose complexation by fatty acids. AB - Comprehensive modelling of a fatty acid molecule inside a VH amylose helix is described. In a first step, the docking of an acetic acid molecule near the helix entry was performed. The low energy solutions were propagated by an iterative procedure involving the sequential addition of single CH2 groups up to a C12 fatty acid followed by energy minimizations. The main result is the superposition of the aliphatic and the helix axes. For the low-energy complexes, the mean plane of the aliphatic carbons has three potential orientations. In each, the aliphatic hydrogens point towards the less crowded regions near the glycosidic oxygens of the amylose. The close packing is due to the related symmetries of both the helix and aliphatic chain. In a second step, the relative roles of the aliphatic part and the polar group were studied separately. For the aliphatic chain, a map based on the two major internal parameters (translation and rotation) along the helix axis shows that the isolated docking solutions are related by a combination of a 60 degrees (360 degrees/6) rotation and a translation of p/6 (p = 0.804 nm corresponds to the pitch of Vhydrate amylose). The H5 glucopyranose atoms participate in close contacts and are responsible for steric conflicts in structures intermediate to the stable docking solutions. The four possible low energy arrangements of the carboxylic group were added to the calculated amylose/aliphatic structures. Two stable conformations of the total fatty acid molecule were determined. For both stable solutions, the polar group is located near the entrance of the helix cavity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8443127 TI - Flexibility in a tetrasaccharide fragment from the high mannose type of N-linked oligosaccharides. AB - An analysis has been carried out of the three-dimensional structure of a tetrasaccharide, Man(alpha 1-3)Man(alpha 1-6)Man(beta 1-4)GlcN Ac beta 1-OCD3, which is a fragment from the high mannose type of N-linked oligosaccharides. Although earlier work had suggested that this fragment might adopt a stable three dimensional structure, both n.m.r. and conformational energy calculations support the existence of an ensemble of structures. The conformational entropy calculated from the ensemble and the distribution of distances between the terminal Man(alpha 1-3) and GlcN Ac residues, however, suggests that a significant fraction of the ensemble has the two terminal residues in close proximity. PMID- 8443128 TI - Conformational features of carrabiose polymers: I. Configurational statistics of kappa-carrageenan. AB - Potential energy functions evaluating both repulsive-attractive van der Waals non bonding interactions and electrostatic interactions have been used to evaluate the conformational energies of the repeating units of the kappa-carrageenan polymers. Structural parameters have been obtained by minimization MNDO procedures (MOPAC). Energy maps have been calculated for the (1-3) alpha-D galactose-4-sulphate (GS) and the (1-4)-3,6-anhydro-alpha-D-galactose (A) residues, taking into account the conformational freedom of the sulphate group. The configurational statistics of the random coiled kappa-carrageenan chain have been explored, disclosing a highly flexible character, which can mainly be ascribed to the random occurrence of two different conformers of the GS-A dimeric unit. PMID- 8443129 TI - Thermal treatment of semi-dilute aqueous xanthan solutions yields weak gels with properties resembling hyaluronic acid. AB - Semi-dilute (ca 2 g/dl) aqueous xanthan (mean molar mass ca 1 x 10(6) g/mol), when heated in the presence of 0.1 M NaCl to a temperature above the order<- >disorder transition temperature, forms highly viscoelastic solutions when returned to room temperature. The steady shear and dynamic rheological behaviour of these solutions discloses a weak gel structure, the viscosity of which is unusually sensitive to the rate of shear. In shear thinning behaviour these heat and salt treated xanthan solutions mimic the properties of the aqueous hyaluronic acid solutions widely used in viscosurgical techniques. The double stranded model of native xanthan is invoked to interpret the observed behaviour of heat and salt treated semi-dilute aqueous xanthan. PMID- 8443130 TI - Miniature crystal models of cellulose polymorphs and other carbohydrates. AB - Miniature crystal models of cellulose and other carbohydrates were evaluated with the molecular mechanics program MM3. The models consisted of groups of 24 to 32 monosaccharide residues, with the models of mono- and disaccharides based on well established, single-crystal work. Structures of the cellulose forms and cellotetraose were based on published work using fibre diffraction methods. A structure for the single-chain I alpha cellulose unit cell was also tested. A dielectric constant of about 4 was best for this type of work. Calculated intra- and intermolecular energy for glucose agreed with literature values for the heat of combustion. Cellulose II had the lowest calculated energy for a cellulose form, followed by I alpha, cellulose III(I), ramie I, IV(II) and IV(I). Optimization of cellulose IV caused larger mean atomic movements from the original crystallographic positions than the other cellulose forms, and cellotetraose had larger movements than any of the other structures. Lattice energies for the cellulose forms were about 20 kcal/mol of glucose residues, with a dominant van der Waals component. PMID- 8443131 TI - Conformational studies of the backbone (poly-N-acetyllactosamine) and the core region sequences of O-linked carbohydrate chains. AB - The AMBER forcefield with added carbohydrate specific parameters for potential types, charges and anomericity has been used to explore the conformational space sampled by oligosaccharides of repeating (Gal beta 1-4GlcNAc beta 1-3)n sequence and those having alpha chain terminating substituents on a Gal beta 1-3GalNAc alpha, O-glycosylated core. The 17 lowest energy forms of the 16-mer N acetyllactosaminic sequence included fully extended units and spring-like coils with dielectric constant 80 to simulate a water environment. More restricted stereochemistry was exhibited by the glycosylation adjacent to the core as has been previously predicted by n.m.r. studies. PMID- 8443132 TI - Steric presentation and recognition of the saccharide chains of glycolipids at the cell surface: favoured conformations of the saccharide-lipid linkage calculated using molecular mechanics (MM3). AB - The orientation of the saccharide moiety of glycolipids at the membrane surface is determined by an interplay of different steric factors, e.g. the conformation of the saccharide chain, the conformation of the saccharide-lipid linkage and restrictions due to the membrane surface. In the present study the preferred conformations of the saccharide-lipid linkages of glucosylceramides with normal and hydroxy fatty acids and glucosyldiglycerides with acyl and alkyl chains were studied using molecular mechanics (MM3). The populations of different conformers were calculated on the basis of relaxed energy maps. Calculations on glucosylceramides at a dielectric constant (epsilon) of 4 showed three dominating conformers: phi/psi/theta 1 = +sc/ap/-sc (global energy minimum), /-sc/ap and +sc/ap/ap, respectively. In sphingolipids the +sc rotamer of theta 1 is disfavoured due to a Hassel-Ottar interaction involving the sphingosine O1 and O3 oxygen atoms. alpha-O Hydroxylation of the fatty acid does not significantly affect the conformational preferences of the saccharide-ceramide linkage at epsilon-values relevant for biomembranes. In glycoglycerolipids the global energy minimum is shifted to the phi/psi/theta 1 = +sc/ap/ap conformation. For glycolipids located in membranes additional steric restrictions are imposed by the surrounding lipid layer. These restrictions in the steric presentation appear to be of crucial significance for the selective recognition and crypticity of glycolipids in membranes. PMID- 8443133 TI - Internal motion in carbohydrates as probed by n.m.r. spectroscopy. AB - In the present study a combination of proton and carbon relaxation rates have been measured for several oligosaccharides at different temperatures. Correlation times, which have been calculated from both sets of data, have been compared in an attempt to establish the relative rate of internal motion. All the data suggest that these motions are not slow with respect to the overall tumbling. PMID- 8443134 TI - Conformations of disaccharides by empirical force field calculations. Part V: Conformational maps of beta-gentiobiose in an optimized consistent force field. AB - A recently optimized set of potential energy functions is used to investigate the conformational flexibility of the beta-(1-->6) glycosidic linkage in beta gentiobiose. Relaxed Ramachandran maps in vacuo are presented in the torsional angles phi and omega, with torsional angle psi allowed to relax freely, as are all other internal degrees of freedom. The study reveals two almost iso-energetic low energy domains in (phi, psi, omega) space, and cross-sections in the low energy domains at omega = -60 degrees and omega = 60 degrees show that more than 60% and 70% respectively of the area of the conformational maps are accessible within 40 kJ mol-1. The molecular structure in the crystal, including the exoanomeric effect, is well reproduced. The structure belongs to the potential energy well which includes the global potential energy minimum in vacuo. The most profound structural difference between the crystal structure and the calculated global minimum in vacuo is the 20 degrees deviation of the psi torsional angle (24 degrees from perfect trans). It occurs in the most flexible glucosidic degree of freedom, psi, and is caused by optimization of the hydrogen bonding network and not by the exoanomeric effect. PMID- 8443135 TI - Macrocyclization of polysaccharides visualized by electron microscopy. AB - Topological features of the polysaccharides schizophyllan, l-carrageenan and gellan gum were studied using electron microscopy. Electron micrographs of schizophyllan not subjected to any thermal or solvent composition history destabilizing the triple helix, show stiff, linear chains consistent with the structure being triple helical and with contour length proportional to the molecular weight in solution. A blend of linear, cyclic and hairpin topologies and higher molecular weight clusters were observed after renaturation, i.e. return to conditions favouring the triple helical structure, from solvent conditions dissociating the triple helix. Electron micrographs of l-carrageenan in salt-free solution reveal linear extended structures. Addition of 0.15 M LiI to the solution before preparation for electron microscopy, i.e. salt conditions that favour ordering but not gelation, yields a large fraction of cyclic structures with circumference of different lengths. Likewise, adding KCl to aqueous gellan gum changes their appearance from dispersed polymers to suprastrands with several associated chains. Macrocyclic species can also be observed in gellan gum after the addition of a gel-promoting salt. The tendency to form macrocyclic structures in competition with intermolecular aggregates is determined by the three factors: (1) chain stiffness relative to overall length; (2) parallel or antiparallel alignment of interacting chain segments; and (3) polymer concentration. The present study indicates that electron microscopy provides information about the topology adopted by polysaccharides. PMID- 8443136 TI - Molecular mechanical parameters (MM2 force field) for the N(sp3)-O(sp3) bond. AB - Based on results of MP2/6-31G* ab initio calculations an MM2 molecular mechanical parameter set has been developed for molecules containing N(sp3)-O(sp3) single bonds, existing parameters concerning the other bonds being retained. The new parameter set was tested for small organic compounds. A simple, generally applicable multilinear regression algorithm has been used and a program written to complement an existing force field (e.g. MM2) with such parameters extracted from quantum chemical computations. PMID- 8443137 TI - Induction of murine macrophage growth by modified LDLs. AB - We previously reported that cell membrane components and lipoproteins were able to induce the growth of murine peritoneal macrophages. The aim of the present study was to examine whether macrophage growth could also be induced by chemically modified lipoproteins, such as acetylated low density lipoprotein (acetyl-LDL) or oxidized LDL, ligands known to be endocytosed by the macrophage scavenger receptors. When murine peritoneal exudate macrophages were cultured in vitro with 25-100 micrograms/mL acetyl-LDL or oxidized LDL, significant growth was induced. On comparing the dose-response curves of these LDLs, a more potent effect was seen with oxidized LDL than acetyl-LDL, especially on resident macrophages. On the other hand, growth of these cells was not stimulated by native (unmodified) LDL or high density lipoprotein. These in vitro data revealed a new function of chemically modified LDLs as effective inducers of macrophage cell growth. This aspect may be physiologically relevant to the growth of macrophage foam cells in situ in the development of atherosclerosis. PMID- 8443138 TI - Localization and smooth muscle cell composition of atherosclerotic lesions in Watanabe heritable hyperlipidemic rabbits. AB - Morphological techniques (histology and electron microscopy), as well as immunofluorescence assays, were applied to the study of the localization and smooth muscle cell (SMC) composition of atherosclerotic lesions in Watanabe heritable hyperlipidemic (WHHL) rabbits during a 4.5-month period. Vascular segments from different arteries (carotid, coronary, and iliac arteries) or from the same vessel at different levels (aorta) of animals at days 7, 15, 30, 40, 60, 90, and 135 showed that the atherosclerotic lesion first became visible at the level of the aortic arch in 60-day-old WHHL animals. Histological examination of serial cryosections from this vascular region indicated that the vascular lesion arose from a cavity in the media layer, located anatomically at the level of the juncture of the ligamentum arteriosum with the aortic arch. This aortic arch cavity is formed during the postnatal closure of the ductus arteriosus and is characterized by the presence of a thickened intima, which was absent in the other vascular regions examined. Immunofluorescence comparison of normal and atherosclerotic tissues from the aortic arch cavity wall with the use of monoclonal antibodies specific for smooth muscle and nonmuscle myosin isoforms revealed the existence of distinct SMC populations. SMCs in the thickened intima showed a myosin isoform pattern peculiar to cells with a degree of maturation intermediate between the fully differentiated and the developing (fetal) aortic SMCs. By contrast, SMCs present in atherosclerotic lesions displayed a predominant fetal-type pattern of myosin isoform expression. The achievement of this myosin isoform content seems to be correlated with the accumulation of lipids in the intima. In the media subjacent to the intimal thickening or atherosclerotic lesion, SMCs primarily displayed an intermediate degree of maturation. In older WHHL animals and at this aortic level, the SMC composition of the atherosclerotic lesion did not change, whereas in the subjacent media, the cells of intermediate type almost disappeared. In the vascular regions in which the atherosclerotic lesion appeared at later stages, such as near the aortic bifurcation, the distribution of fetal and intermediate cell types in the atherosclerotic wall was similar to that taken at the aortic arch level. These results indicate that there is 1) a preferential anatomic site from which atherogenesis initiates in WHHL rabbits; 2) a time correlation between the accumulation of lipids in the wall and the phenotypic change of SMCs toward a poorly differentiated cell type; and 3) the tendency for SMCs to follow the same differentiation pattern in early atherosclerotic lesions, irrespective of the site and time at which they develop. PMID- 8443139 TI - A new anti-inflammatory leucine derivative, NPC-15669, inhibits growth of cultured human aortic smooth muscle cells. AB - We have observed that NPC-15669, a leucine derivative with anti-inflammatory activity, reduced the proliferation of human aortic smooth muscle cells (HASMCs) in culture. We used a colorimetric assay and tritiated thymidine to measure the cell density and proliferation of HASMC cultures treated with this agent. We also studied the effect of NPC-15669 on the proliferation and migration of human aortic endothelial cells (HAECs). Subconfluent HASMC cultures were growth arrested for 2 days. On the third day, growth was stimulated with either growth media (medium M199 containing 10% fetal bovine serum [FBS]), human platelet derived growth factor (hPDGF), or fibroblast growth factor (FGF) in the absence or presence of NPC-15669 (0.1-50 microM). Regardless of the stimulating agent for HASMCs (FBS, hPDGF, or FGF), NPC-15669 at concentrations of 10-25 microM caused a significant reduction in thymidine incorporation (36.7% and 77.2% in 10 microM and 25 microM, respectively; p < 0.005) and cell density (25-87%, p < 0.001) compared with control. NPC-15669 did not, however, have an effect on the rate of proliferation or migration of HAECs, even at concentrations up to 50 microM. Two other anti-inflammatory agents, aspirin and dexamethasone, caused substantially and significantly less inhibition, even at high concentrations (50 and 25 microM, respectively). This study demonstrates that in vitro, NPC-15669 significantly inhibits HASMC proliferation but has no effect on proliferation or migration of HAECs. PMID- 8443140 TI - Insulin resistance, glucose intolerance, and hyperinsulinemia. Hypertriglyceridemia versus hypercholesterolemia. AB - Plasma glucose and insulin responses to oral glucose and mixed meals and the ability of insulin to stimulate glucose disposal were quantified in normal volunteer subjects and patients with types IIA, IIB, and IV hyperlipoproteinemia (HLP). The results indicated that patients with either type IIB or IV HLP had higher plasma glucose (p < 0.05-< 0.001) and insulin (p < 0.001) responses to both oral glucose and mixed meals compared with the normal subjects and patients with type IIA HLP. Steady-state plasma glucose concentrations (mmol/L) were also higher (p < 0.001) in patients with types IIB (13.3 +/- 0.6) and IV (12.8 +/- 1.2) HLP during a continuous infusion of somatostatin, glucose, and insulin than either the control group (volunteer subjects) (6.2 +/- 0.9) or patients with type IIA HLP (5.6 +/- 1.0). Because the steady-state plasma insulin concentrations were similar in all four groups, patients with either type IIB or IV HLP were resistant to insulin-mediated glucose uptake. These data indicate that patients with hypertriglyceridemia are insulin resistant, glucose intolerant, and hyperinsulinemic, irrespective of the plasma cholesterol concentration. The results further demonstrate that hypercholesterolemic patients with normal triglyceride concentrations do not have any abnormalities of glucose and insulin metabolism. PMID- 8443141 TI - Protection from atherosclerosis in vein grafts by a rigid external support. AB - Atherosclerosis is a common feature of autogenous vein bypass grafts resulting in their long-term failure. Arterial pressure-induced distension is thought to play a major role in the wall thickening of vein grafts, which may in turn favor atherosclerotic complications. In this study, we evaluated the influence of vein distension on the development of atherosclerotic lesions in jugular vein grafts interposed into the common carotid arteries of rabbits. The proximal half of each vein graft was wrapped with a 4-mm-diameter polytetrafluoroethylene graft that reduced the vein graft diameter by 46 +/- 5%. Fourteen animals were fed a 1% cholesterol-rich diet for 8 weeks, and five animals were fed a normal diet. In normocholesterolemic and hypercholesterolemic animals, the wall thickness and the total cross-sectional area were significantly reduced in wrapped compared with unwrapped segments. Foam cells were never observed in normocholesterolemic animals. In hypercholesterolemic rabbits, the sudanophilic lesions covered 62 +/- 4% of the luminal surface in unwrapped segments and 31 +/- 7% in wrapped segments (p < 0.0001). In transverse sections, the surface areas of foam cells were also markedly reduced in wrapped compared with unwrapped segments. Reduction of the wall distension using a rigid external support protected the vein grafts from atherosclerosis, possibly as a result of the decrease in wall thickening that occurred in response to arterialization. PMID- 8443143 TI - Shear-induced platelet aggregation is potentiated by desmopressin and inhibited by ticlopidine. AB - Shear-induced platelet aggregation is important in physiological hemostasis and in the pathogenesis of arterial thrombosis. It requires extracellular Ca2+, platelet membrane glycoproteins Ib/IX and IIb/IIIa, von Willebrand factor (vWF), and ADP. We studied the effects of desmopressin (DDAVP), which increases plasma vWF levels and shortens the bleeding time, and of ticlopidine, which inhibits platelet responses to ADP, on shear-induced platelet aggregation. Eleven healthy volunteers were given oral ticlopidine (250 mg b.i.d.) for 7 days. The same subjects were infused intravenously with DDAVP (0.3 micrograms/kg body wt) before the first and after the last doses of ticlopidine. The degree of platelet aggregation induced by shear stress at 25, 50, 75, and 100 dyne/cm2 in a cone-and plate viscometer, plasma vWF levels, and the bleeding time were measured before and after each DDAVP infusion. Plasma vWF levels and the extent of shear-induced platelet aggregation increased after DDAVP and were correlated. Ticlopidine partially inhibited shear-induced platelet aggregation both before and after DDAVP infusion. The bleeding time, prolonged by ticlopidine, was shortened by DDAVP. Potentiation by DDAVP of shear-induced platelet aggregation may be one mechanism by which the drug shortens the prolonged bleeding time. Since shear induced platelet aggregation can cause thrombotic occlusions in stenotic arterial vessels, our findings may explain the therapeutic efficacy of ticlopidine in arterial thrombosis. PMID- 8443142 TI - Decreased postprandial response to a fat meal in normotriglyceridemic men with hypoalphalipoproteinemia. AB - The plasma level of high density lipoprotein cholesterol (HDL-C) has been reported to be inversely correlated with the level of triglycerides (TGs) and the magnitude of postprandial lipemia because subjects with low HDL-C accompanying high TG levels often have an increased postprandial response to a fat load. However, information is limited regarding the postprandial response to a fat load in subjects with low HDL-C and normal fasting TG values (hypoalphalipoproteinemia [hypoalpha]). We administered an oral fat load (70 g/m2 of body surface area) to six subjects with hypoalpha and six aged-matched control subjects. Plasma levels of lipids and lipoproteins and the mass of triglyceride-rich lipoproteins (TRLs: Sf > 100 and Sf 20-100) were measured every 2 hours for 8 hours. The mass and chemical composition of Sf > 100 or Sf 20-100 TRLs were not different between the fasting groups; postprandial Sf > 100 but not Sf 20-100 TRLs (mean +/- SD) was significantly lower in subjects with hypoalpha (200.4 +/- 64.8 mg/dL versus 110.6 +/- 50.9 mg/dL; analysis of variance, F test, p = 0.04). In the hypoalpha subjects, the compositions of postprandial Sf > 100 TRLs were TG poor and cholesterol and phospholipid enriched (p < 0.001) while the Sf 20-100 TRLs were enriched in cholesterol and phospholipid but relatively protein depleted (p = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8443144 TI - Localization of von Willebrand factor binding domains to endothelial extracellular matrix and to type VI collagen. AB - We have recently shown that von Willebrand factor (vWF) binds to endothelial and fibroblastic extracellular matrixes (ECM) in a dose-dependent, specific, and saturable way. To localize the domain on the vWF subunit responsible for this interaction, purified proteolytic fragments of vWF were compared for their ability to inhibit 125I-vWF binding to ECM. A tryptic dimeric fragment of 116 kD (T116), extending from amino acid (aa) residues 449 to 728, produced a significant inhibition of 125I-vWF binding to the ECM. In contrast, P34 (aa 1 272), SpI (aa 911-1,365), and SpII (aa 1,366-2,050) had no significant effect on 125I-vWF binding to the ECM. Using an immunofluorescence technique, we identified type VI collagen and heparan sulfate in the endothelial ECM. 125I-vWF was found to bind specifically to purified type VI collagen. Unlabeled vWF and SpIII were able to completely inhibit 125I-vWF binding to type VI collagen. T116 and SpI appeared as competitors of this interaction, whereas P34 and SpII were not. Our data suggest that vWF binds to the endothelial ECM through the T116 fragment and that T116 and SpI each contain a binding site for type VI collagen. Heparin is known to be a vWF ligand, but did not appear as a competitor of vWF binding to the ECM, nor did heparan sulfate. PMID- 8443145 TI - Plasminogen activator inhibitor activity in diabetic and nondiabetic survivors of myocardial infarction. AB - Recent studies suggest that plasminogen activator inhibitor (PAI-1) may be a risk factor for recurrent myocardial infarction. We measured PAI-1 activity and antigen and tissue-type plasminogen activator (t-PA) antigen in 35 (20 nondiabetic and 15 diabetic) subjects with no clinical or electrocardiographic evidence of ischemic heart disease and in 74 (50 nondiabetic and 24 diabetic subjects) who had survived a myocardial infarction in the preceding 6-24 months. Levels of PAI-1 activity (18.7 +/- 5.6 versus 12.0 +/- 3.8 arbitrary units [AU] per milliliter, p = 0.001) and t-PA antigen (7.0 +/- 1.9 versus 4.6 +/- 2.0 ng/mL, p = 0.001) were significantly higher in diabetic compared with nondiabetic control subjects. Survivors of myocardial infarction had higher levels of PAI-1 activity and antigen and t-PA antigen than control subjects, and the diabetic survivors had higher levels of PAI-1 activity (25.3 +/- 6.7 versus 20.1 +/- 7.1 AU/mL, p = 0.004) and t-PA antigen (10.6 +/- 4.3 versus 8.4 +/- 3.3 ng/mL, p = 0.03) than the nondiabetic survivors. No difference in PAI-1 antigen levels was found between the diabetic subjects and either the nondiabetic control subjects or survivors of myocardial infarction. After venous occlusion in control subjects, there was a significant increase in PAI-1 antigen (mean 26.7%, range 14.1-58.1% in nondiabetics and mean 25.2%, range 6.2-39.7% in diabetics) and t-PA antigen (mean 78.3%, range 13.6-186.2% for nondiabetic and mean 40.7%, range 17.5 76.2% for diabetic subjects), but in the survivors of myocardial infarction, no significant effect of venous occlusion was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8443146 TI - Increased in vivo production of thromboxane in patients with sickle cell disease is accompanied by an impairment of platelet functions to the thromboxane A2 agonist U46619. AB - Thrombosis represents an important cause of mortality in patients with sickle cell disease, in addition to the complications caused by the primary defect of inherited abnormal hemoglobin. To study the involvement of platelets in these complications, we assessed the biosynthesis of thromboxane A2 in samples from 49 patients with sickle cell disease and in 33 control subjects. The urinary excretion of the major arachidonic acid metabolite of platelet origin (11-dehydro thromboxane B2) and of the vascular endothelial cell (2,3-dinor-6 ketoprostaglandin F1 alpha) were very significantly increased (p < 0.0002) in the patients. In a small group of patients (n = 14), we further investigated the ex vivo response of their platelets to U46619, a stable analogue of thromboxane A2. We observed decreased aggregation and [14C]serotonin release compared with control (p < 0.05); similarly, we found impaired p47 protein phosphorylation (p < 0.05). In contrast, platelets from these patients responded normally to thrombin (0.1 unit/mL). In vivo desensitization of platelets from these patients to thromboxane may constitute a form of regulation that may prevent the propagation of aggregation by this potent inducer, as has been hypothesized in in vitro studies. Our results may also provide a rationale for using antiplatelet drugs in the prophylaxis of thrombotic complications in sickle cell patients. PMID- 8443147 TI - Plasma triglyceride and LDL heterogeneity in familial combined hyperlipidemia. AB - Familial combined hyperlipidemia (FCHL) is a genetic disorder characterized by increases in plasma cholesterol and/or triglyceride, elevated apolipoprotein B, and heterogeneous low density lipoprotein (LDL). To examine the relation between plasma triglyceride concentrations and LDL heterogeneity, 13 hypertriglyceridemic FCHL patients with a predominance of small LDL (LDL subclass phenotype B) were treated with gemfibrozil. The distribution of LDL was determined using nondenaturing gradient gel electrophoresis and nonequilibrium density gradient ultracentrifugation. Mean plasma triglyceride levels decreased 55% (p < 0.01) after 3 months of treatment. Mean LDL peak particle size remained small (247 +/- 4 versus 249 +/- 5 A), and the correlation between change in plasma triglyceride concentrations and a change in LDL peak particle size was not significant. Individual changes in LDL flotation rate (Rf) were, however, inversely correlated with changes in triglyceride concentration (R = 0.60, p < 0.05). Although mean LDL Rf increased during treatment (p < 0.005) due to an increase in buoyant LDL, dense LDL remained elevated compared with that of a control population. Thus in FCHL patients, small, dense LDL persists despite decreases in plasma triglyceride concentrations. PMID- 8443148 TI - Prostacyclin agonists reduce early atherosclerosis in hyperlipidemic hamsters. Octimibate and BMY 42393 suppress monocyte chemotaxis, macrophage cholesteryl ester accumulation, scavenger receptor activity, and tumor necrosis factor production. AB - We determined the effects of two prostacyclin agonists (octimibate and BMY 42393) on the progression of the fatty streak in vivo and on macrophage function in vitro. Hamsters were fed chow plus 0.05% cholesterol and 10% coconut oil. Control hamsters were compared with animals receiving either octimibate (10 or 30 mg/kg per day) or BMY 42393 (30 mg/kg per day). After 10 weeks of treatment, octimibate decreased plasma total cholesterol and triglycerides by 43% and 32%, respectively. Neither agonist affected blood pressure or heart rate. Lesion-prone aortic arches were stained with hematoxylin and oil red O and examined en face. Compared with controls, octimibate and BMY 42393 on average decreased mononuclear cells attached to the luminal surface by 44% and reduced subendothelial macrophage-foam cell number by 56%, foam cell size by 38%, and fatty streak area by 63%. Since octimibate is a putative inhibitor of acyl coenzyme A cholesterol acyltransferase, we studied the effect of both agents on cholesteryl ester metabolism in murine macrophages. At 10 microM, octimibate and BMY 42393 decreased cholesteryl ester accumulation in macrophages by 90% and 41%, respectively. Octimibate inhibited cholesteryl ester synthesis by 96% and increased the rate of cholesteryl ester degradation by 52%. Both prostacyclin agonists reduced macrophage scavenger receptor-mediated uptake of acetylated low density lipoprotein by 24-66% and increased cyclic adenosine monophosphate levels. Octimibate and BMY 42393 inhibited the secretion of tumor necrosis factor by 80-88% when macrophages were activated with lipopolysaccharide. At 10 microM, both agents decreased human monocyte chemotaxis to N-formyl-methionyl-leucyl phenylalanine by 64-79%. The in vitro results with octimibate and BMY 42393 are consistent with the low number of small foam cells quantified in vivo. We suggest that octimibate and BMY 42393 suppress monocyte-macrophage atherogenic activity and cytokine production and thus inhibit the development of early atherosclerosis. PMID- 8443149 TI - Cell-derived unesterified cholesterol cycles between different HDLs and LDL for its effective esterification in plasma. AB - Pulse-chase incubations of human plasma with [3H]cholesterol-laden skin fibroblasts or low density lipoproteins (LDL) and nondenaturing two-dimensional electrophoresis were used to study the transfer and esterification of cell derived unesterified cholesterol (UC) in human plasma lipoproteins. Specific radioactivities ([3H]UC per microgram of UC) were calculated, and net cholesterol mass transfer was quantified using a fluoro-enzymatic assay to validate productive transfers of UC between high density lipoprotein (HDL) and LDL. Cellular UC was initially taken up by pre-beta 1-HDL and subsequently transferred in the sequence pre-beta 2-HDL-->pre-beta 3-HDL-->alpha-HDL-->LDL. During the first 5 minutes of this process, only 5% of cellular cholesterol was esterified in pre-beta 3-HDL and alpha-HDL; the remainder reached LDL as UC. Cellular UC accumulating in LDL was then redistributed to various HDL particles via two pathways: 1) the partially LDL receptor-mediated uptake and re-secretion of UC by cells and 2) the direct transfer of UC to HDL, mostly to alpha-HDL and a small amount to pre-beta-HDL. UC was not transferred from LDL to HDL after inhibition of lecithin:cholesterol acyltransferase (LCAT). The esterification of cellular [3H]cholesterol in plasma was competitively inhibited by the addition of excess unlabeled LDL but not of excess HDL. However, both excess LDL and excess HDL prevented the esterification of cell-derived cholesterol in apolipoprotein B-free plasma. This demonstrated that LDL is the major source of UC to the LCAT reaction and that the transfer of UC from LDL to HDL is LCAT dependent. In conclusion, the effective esterification of cell-derived cholesterol in plasma involves a rapid transfer of UC via HDL particles to LDL, from which it is distributed to pre-beta HDL and alpha-HDL. Furthermore, we hypothesize that the transfer per se of cellular UC to LDL forms a cholesterol concentration gradient between cell membranes and HDL and thus a second, reverse cholesterol transport mechanism in addition to the esterification of cholesterol by LCAT. PMID- 8443150 TI - Studies on the structure of complement C3 and the stability of C3 derived phagocytic ligands C3b/iC3b in SJL/J and BALB/c mice. AB - Female SJL/J mice are more susceptible to development of experimental autoimmune myositis than most other mouse strains. Since complement has been implicated in the pathogenesis of inflammatory muscle disease in humans, quantitative and qualitative studies of complement C3 were undertaken in SJL/J and BALB/c mice to determine whether complement may influence disease susceptibility in SJL/J mice. In accordance with previous studies, mature male and female BALB/c mice were shown to have similar serum C3 concentrations. However, differences were found between mature male and female SJL/J mice. Male SJL/J mice have significantly higher serum C3 concentrations than SJL/J females and both sexes of BALB/c mice suggesting that serum C3 concentration may be variably influenced by sex in some mouse strains. Qualitatively, SJL/J mice were shown to have a different allotypic form of C3 (C3F) compared to the common electrophoretically slow form (C3S) found in BALB/c mice and most other mouse strains. Furthermore, studies on the decay rate of C3 revealed that C3b/iC3b fragments are converted to C3c/d at a faster rate in sera from female SJL/J mice compared to female BALB/c mice. Because removal and solubility of immune complexes is influenced by complement C3, it is possible that the more rapid decay of the phagocytic ligands C3b/iC3b may account for the increased susceptibility to development of autoimmune disease in female SJL/J mice. PMID- 8443151 TI - HLA class I nucleotide sequences, 1992. PMID- 8443152 TI - HLA class II nucleotide sequences, 1992. PMID- 8443153 TI - Identification of the Cl(-)-binding site in the human red and green color vision pigments. AB - Chloride ions are known to bind and alter the absorption spectra of some but not all visual pigments. In this report, the human red and green color vision pigments are shown to bind Cl- and to undergo a large red shift in their absorption maxima. Mutation of 18 different positively charged amino acids in these pigments identified two residues, His197 and Lys200, in the Cl(-)-binding site. His197 and Lys200 are strictly conserved in all long-wavelength cone pigments but are absent in all rhodopsins and short-wavelength cone pigments. This fact suggests that the evolutionary branch of the long-wavelength pigments was established when an ancestral pigment acquired the ability to bind Cl- and, as a result, shift the absorption maximum to longer wavelengths. PMID- 8443154 TI - Solution conformation of cobrotoxin: a nuclear magnetic resonance and hybrid distance geometry-dynamical simulated annealing study. AB - The solution conformation of cobrotoxin has been determined by using proton nuclear magnetic resonance spectroscopy. With the combination of various two dimensional NMR techniques, the 1H-NMR spectrum of cobrotoxin was completely assigned (Yu et al., 1990). A set of 435 approximate interproton distance restraints was derived from nuclear Overhauser enhancement (NOE) measurements. These NOE constraints, in addition to the 29 dihedral angle constraints (from coupling constant measurements) and 26 hydrogen bonding restraints (from the pattern of short-range NOEs), form the basis of 3-D structure determination by the hybrid distance geometry-dynamical simulated annealing method. The 23 structures that were obtained satisfy the experimental restraints, display small deviation from idealized covalent geometry, and possess good nonbonded contacts. Analysis of converged structures indicated that there are two antiparallel beta sheets (double and triple stranded), duly confirming our earlier observations. These are well defined in terms of both atomic root mean square (RMS) differences and backbone torsional angles. The average backbone RMS deviation between the calculated structures and the mean structure, for the beta-sheet regions, is 0.92 A. The mean solution structure was compared with the X-ray crystal structure of erabutoxin b, the homologous protein. This yielded information that both structures resemble each other except at the exposed loop/surface regions, where the solution structure seems to possess more flexibility. PMID- 8443155 TI - Substrate-specific enhancement of the oxidative half-reaction of monoamine oxidase. AB - Monoamine oxidases A and B have identical flavin sites but different, although overlapping, amine substrate specificity. Reoxidation of ternary complexes containing substrate is much faster than of free enzyme, and the enhancement is greater in the A form than the B form. The oxidative half-reaction was studied with a variety of substrates to elucidate the specificity of the effect and to probe the different influences of substrate on the flavin reoxidation in the two forms of the enzyme. The second-order rate constant for the reoxidation was highest with monoamine oxidase A when kynuramine was the ligand (508 x 10(3) M-1 s-1) compared to 4 x 10(3) M-1 s-1 in its absence. MPTP (166 x 10(3) M-1 s-1) also enhanced reoxidation well, but indole substrates stimulated only poorly (e.g., tryptamine, 29 x 10(3) M-1 s-1; serotonin, 50 x 10(3) M-1 s-1). For the A form, the reduction of the flavin was rate-limiting in all cases. For the B form, reoxidation was rate-limiting for beta-phenylethylamine and contributed to the determination of the overall rate with several substrates. The ratio of the enhanced rate of oxidation to the rate of reduction correlated with the redox state of the enzyme in turnover experiments. All the observations are consistent with alternate paths of reoxidation, via either free enzyme or a reduced enzyme substrate complex. The flux through each path is determined by the relative dissociation constants and rate constants. PMID- 8443156 TI - Assignment of 1H, 15N, and 13C resonances, identification of elements of secondary structure and determination of the global fold of the DNA-binding domain of GAL4. AB - Almost complete assignments of the 1H, 15N, and aliphatic 13C resonances of the 62-residue N-terminal DNA-binding domain of GAL4 [GAL4(62)] have been obtained using a combination of two-dimensional homonuclear and two- and three-dimensional double- and triple-resonance heteronuclear NMR methods. The sequential NOE connectivities, amide proton exchange measurements, and 13C alpha chemical shift data indicate the presence of two short alpha-helices in the N-terminal half of the polypeptide. Residues 1-9 and 41-62 appear to be unstructured and flexible in solution. Analysis of the 13C alpha chemical shifts also revealed a significant downfield shift of approximately +3 ppm, relative to random-coil values, for the four nonbridging Zn(II) ligands, Cys 14, 21, 31, and 38. Interestingly, no such correlation was observed for the two bridging ligands, Cys 11 and 28. Preliminary structure calculations using a subset of distance restraints derived from three dimensional 1H-15N and 1H-13C NOESY-HSQC spectra are consistent with the recently reported solution structures of Zn(II)2GAL4(7-49) [Kraulis, P., et al. (1992) Nature 356, 448-450] and of Cd(II)2GAL4(65) [Baleja, J. D., et al. (1992) Nature 356, 450-453]. PMID- 8443157 TI - Crystal structure of the catalytic subunit of cAMP-dependent protein kinase complexed with MgATP and peptide inhibitor. AB - The structure of a ternary complex of the catalytic subunit of cAMP-dependent protein kinase, MgATP, and a 20-residue inhibitor peptide was determined at a resolution of 2.7 A using the difference Fourier technique starting from the model of the binary complex (Knighton et al., 1991a). The model of the ternary complex was refined using both X-PLOR and TNT to an R factor of 0.212 and 0.224, respectively. The orientation of the nucleotide and the interactions of MgATP with numerous conserved residues at the active site of the enzyme are clearly defined. The unique protein kinase nucleotide binding site consists of a five stranded antiparallel beta-sheet with the base buried in a hydrophobic site along beta-strands 1 and 2 and fixed by hydrogen bonds to the N6 amino and N7 nitrogens. The small lobe secures the nucleotide via a glycine-rich loop and by ion pairing with Lys72 and Glu91. While the small lobe fixes the nontransferable alpha- and beta-phosphates in this inhibitor complex, the gamma-phosphate is secured by two Mg2+ ions and interacts both directly and indirectly with several residues in the large lobe--Asp184, Asn171, Lys168. Asp166 is positioned to serve as a catalytic base. The structure is correlated with previous chemical evidence, and the features that distinguish this nucleotide binding motif from other nucleotide binding proteins are delineated. PMID- 8443158 TI - Protein anatomy: spontaneous formation of filamentous helical structures from the N-terminal module of barnase. AB - This paper reports the conformation of the N-terminal module (24 amino acid residues) of barnase in aqueous solution. This module contains the first of three helices in the intact protein. Circular dichroism spectra showed the peptide fragment to have a predominantly random coil structure immediately following dissolution in aqueous solution and to be gradually converted to a helical structure at 5 degrees C. This was mediated by aggregation, and an electron micrograph indicated the aggregate to be comprised of filamentous helical structures. Scanning tunneling microscopy showed the filamentous structures to be made up of protofilamentous structures containing many disks apparently stacked on top of each other. A monomer of the peptide predominantly took on a random coil conformation in aqueous solution and the multimer, a stable helical structure. A local amino acid sequence would thus appear to determine the secondary structure corresponding to that in a native protein but stability to be governed by other factors such as tertiary interactions. Helical wheel representation indicated the peptide fragment to have the features of an amphiphilic helix. Hydrophobic burial may provide the driving force for producing a stable helical structure in aqueous solution. PMID- 8443159 TI - Specific recognition of CG base pairs by 2-deoxynebularine within the purine.purine.pyrimidine triple-helix motif. AB - The sequence-specific recognition of double-helical DNA by oligodeoxyribonucleotide-directed triple-helix formation is limited mostly to purine tracts. Within the geometric constraints of the phosphate-deoxyribose position of a purine-purine-pyrimidine triple-helical structure, model building studies suggested that the deoxyribonucleoside 2'-deoxynebularine (dN) might form one specific hydrogen bond with cytosine (C) or adenine (A) of Watson-Crick cytosine-guanine (CG) or adenine-thymine (AT) base pairs. 2-Deoxynebularine (dN) was incorporated by automated methods into purine-rich oligodeoxyribonucleotides. From affinity cleavage analysis, the stabilities of base triplets within a purine.purine.pyrimidine (Pu.Pu.Py) triple helix were found to decrease in the order N.CG approximately N.AT >> N.GC approximately N.TA (pH 7.4, 37 degrees C). Oligodeoxyribonucleotides containing two N residues were shown to bind specifically within plasmid DNA a single 15 base pair site of the human immunodeficiency virus genome containing two CG base pairs within a purine tract. This binding event occurs under physiologically relevant pH and temperature (pH 7.4, 37 degrees C) and demonstrates the utility of the new base. Quantitative affinity cleavage titration reveals that, in the particular sequence studied, an N.CG base triplet interaction results in a stabilization of the local triple helical structure by 1 kcal.mol-1 (10 mM NaCl, 1 mM spermine tetrahydrochloride, 50 mM Tris-acetate, pH 7.4, 4 degrees C) compared to an A.CG base triplet mismatch. PMID- 8443160 TI - Influence of nitrogen, oxygen, and nitroimidazole radiosensitizers on DNA damage induced by ionizing radiation. AB - Oxygen and nitroaromatic compounds are known to enhance the sensitivity of cells to ionizing radiation. Employing calf thymus DNA and oligo(dA)12/poly(dT), we have examined the differences to DNA damage, in particular thymine glycols and the 3'-DNA termini at strand breaks, arising from irradiation under anoxic and oxic conditions and the presence and absence of misonidazole [1-(2-nitro-1 imidazoyl)-3-methoxy-2-propanol]. We show that (i) irradiation under nitrogen generates strand breaks almost exclusively with 3'-phosphate termini; (ii) irradiation under oxic conditions increases the yield of strand breaks 3-fold, and the 3' termini consist of 3'-phosphoglycolate and 3'-phosphate end groups in a ratio of approximately 1.6; (iii) the patterns of base and sugar damage detectable by a postlabeling assay [Weinfield, M., & Soderlind, K.-J. (1991) Biochemistry 30, 1091-1097] differ completely between DNA irradiated under oxic vs anoxic conditions; (iv) the presence of misonidazole under anoxic conditions does not increase the level of strand breakage but, like oxygen, significantly enhances the formation of 3'-phosphoglycolate end groups; (v) the presence of misonidazole during anoxic irradiation does not increase the yield of any other type of 'oxic' damage detectable by the postlabeling assay, such as thymine glycols; and (vi) misonidazole at concentrations greater than 50 microM affords significant protection to naked DNA, probably by OH radical scavenging, and both the nitroaromatic ring and methoxyisopropanol side chain contribute to this protective action. PMID- 8443161 TI - Binding of a protein-tyrosine phosphatase to DNA through its carboxy-terminal noncatalytic domain. AB - The noncatalytic domain of a non-receptor-type protein-tyrosine phosphatase (the T-cell phosphatase or PTP-S) isolated from a rat spleen cDNA library shows homology with the basic domains of transcription factors Fos and Jun [Swarup, G., Kamatkar, S., Radha, V., & Rema, V. (1991) FEBS Lett. 280,65-69]. We have expressed this phosphatase in Escherichia coli under the control of T7 promoter. The PTP-S gene product expressed in E. coli shows protein-tyrosine phosphatase activity and binds to DNA at pH 7.4 as determined by DNA affinity chromatography, Southwestern blotting, and gel retardation methods. The carboxy-terminal region of this phosphatase was fused with glutathione S-transferase by constructing expression vectors. Experiments using fusion proteins with glutathione S transferase suggest that the carboxy-terminal 57 amino acids of PTP-S are sufficient for DNA binding. Deletion of the C-terminal 57 amino acids of PTP-S protein abolished its DNA binding property, as determined by Southwestern blotting, but not its enzymatic activity. This suggests that the C-terminal 57 amino acids are essential for the DNA binding function of this protein but not for its enzymatic activity. Another non-receptor-type protein-tyrosine phosphatase, PTP-1, when expressed in enzymatically active form in E. coli did not bind to DNA. These results suggest that a nontransmembrane protein-tyrosine phosphatase, PTP-S, binds to DNA in vitro through its carboxy-terminal noncatalytic region. PMID- 8443162 TI - CO recombination to human myoglobin mutants in glycerol-water solutions. AB - The kinetics of CO recombination to site-specific mutants of human myoglobin have been studied by flash photolysis in the temperature range 250-320 K on the nanosecond to second time scale in 75% glycerol at pH 7. The mutants were constructed to examine specific proposals concerning the roles of Lys 45, Asp 60, and Val 68 in the ligand binding process. It is found that ligand recombination is nonexponential for all the mutants and that both the geminate amplitude and rate show large variations. The results are interpreted in terms of specific models connecting the dynamics and structure. It is shown that removal of the charged group at position 45 does not substantially affect the barrier height for escape or entry of the ligand; therefore the breakage of the salt bridge linking Lys 45, Asp 60, and a heme propionate is ruled out as the rate-determining barrier for this process. On the other hand, it is found that the escape barrier decreases roughly as size of the residue at position 68 increases, in the order Ala > Val > Asn > Leu. The residue at position 68 is also a major contributor to the final barrier to rebinding, but the barrier height shows no correlation with residue size and is more dependent on the stereochemistry of the residue. A molecular mechanism for ligand binding that is consistent with the results is discussed, and supporting evidence for this mechanism is examined. PMID- 8443163 TI - Photoinactivation of the bovine heart mitochondrial F1-ATPase by [14C]dequalinium cross-links phenylalanine-403 or phenylalanine-406 of an alpha subunit to a site or sites contained within residues 440-459 of a beta subunit. AB - Synthesis of [14C]dequalinium, 1,1'-(1,10-[1,10-14C]decanediyl)bis[4-amino-2 methylquinolinium ], is described, which photoinactivates the bovine heart mitochondrial F1-ATPase (MF1). Maximal photoinactivation occurs on incorporation of about 1.5 mol of [14C]dequalinium/mol of MF1. Three radioactive species were resolved when photoinactivated enzyme was submitted to polyacrylamide gel electrophoresis at pH 4.0 in the presence of tetradecyltrimethylammonium bromide, which correspond to the alpha and beta subunits and a cross-linked species with an M(r) of 116,000. Fractionation of a tryptic digest of photoinactivated enzyme by high-performance liquid chromatography led to isolation of a radioactive peptide which contains residues 399-420 of a alpha subunit. Two fragments containing equal amounts of radioactivity were obtained on fractionation of an endoproteinase Asp-N digest of the isolated radioactive tryptic peptide by high performance liquid chromatography. Amino acid sequence analysis showed that both fragments contained residues 399-408 of the alpha subunit, but one was missing Phe-alpha 403 and the other was lacking Phe-alpha 406. Fractionation of a cyanogen bromide digest of photoinactivated enzyme followed by trypsin digestion of partially purified cyanogen bromide fragments and fractionation of the resulting radioactive tryptic fragments yielded several radioactive species comprised of residues 399-420 of the alpha subunit cross-linked to residues 440 459 of the beta subunit and a radioactive fragment containing residues 399-420 of the alpha subunit. Partial sequence analyses of the cross-linked fragments suggest that Phe-alpha 403 and Phe-alpha 406 participate in cross-links, whereas no information was obtained on the site or sites of cross-linking in the beta subunit fragment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8443164 TI - Purification of a nitric oxide-stimulated ADP-ribosylated protein using biotinylated beta-nicotinamide adenine dinucleotide. AB - ADP-ribosylation, involving the transfer of an ADP-ribose moiety from NAD to proteins, is mediated by several bacterial toxins and endogenous ADP ribosyltransferases. We report here the synthesis of biotinylated NAD and its use to label and purify biotinyl-ADP-ribosylated proteins. We demonstrate that biotinylated NAD can be used by diphtheria toxin to biotinylate elongation factor 2. Using avidin affinity chromatography, we have purified a protein whose ADP ribosylation is enhanced by nitric oxide and which has been identified as glyceraldehyde-3-phosphate dehydrogenase. PMID- 8443165 TI - Spectroscopic detection of chemical intermediates in the reaction of para substituted benzylamines with bovine serum amine oxidase. AB - Anaerobic, rapid-scanning stopped-flow spectroscopy has been used to investigate the UV-visible absorbance changes (300-540 nm) that occur in the spectrum of bovine serum amine oxidase during reduction by benzylamine, p-hydroxybenzylamine, and p-methoxybenzylamine. The reaction of enzyme with benzylamine generates detectable relaxations at 310, 340, and 480 nm, which are attributed to the production of reduced cofactor (310 and 480 nm) and to an enzyme-substrate Schiff base complex (340 nm). Additional transients have been observed at 440, 425, and 460 nm with p-hydroxybenzylamine, p-methoxybenzylamine, and p-(N,N dimethylamino)benzylamine, respectively. These relaxations are ascribed to quinonoid species, formed reversibly from Schiff base complexes between oxidized product and reduced cofactor. With the spectral detection of enzyme-product Schiff base complexes, evidence now exists for each of the postulated chemical intermediates along the reaction path of bovine serum amine oxidase [cf. Hartmann, C., & Klinman, J. P. (1991) Biochemistry 30, 4605]. Anaerobic, single wavelength stopped-flow data, collected in conjunction with rapid-scanning studies for benzylamine and p-hydroxy-benzylamine, provide approximate rate constants for each of the kinetic processes corresponding to enzyme-substrate Schiff base formation, to enzyme reduction, and to the formation and decay of the quinonoid intermediate. PMID- 8443166 TI - Identification of the S-adenosyl-L-methionine binding site of protein-carboxyl O methyltransferase using 8-azido-S-adenosyl-L-methionine. AB - Protein-carboxyl O-methyltransferase (protein methylase II) transfers the methyl group from S-adenosyl-L-methionine (AdoMet) to the carboxyl side chains of the amino acids in the proteins. We have used the radiolabeled analogue of AdoMet, 8 azido-S-adenosyl-L-[methyl-3H]methionine (8-N3-Ado[methyl-3H]Met), to investigate the AdoMet binding site of protein methylase II. The incorporation of the photoaffinity label in the enzyme upon UV irradiation is highly specific. In the absence of UV irradiation or if the photoprobe is irradiated prior to its addition to the reaction mixture, no photoinsertion of the label occurs. Moreover, the presence of a competitive inhibitor of protein methylase II, S adenosyl-L-homocysteine (AdoHcy), or the unlabeled AdoMet itself in the reaction mixture diminished labeling of the enzyme. Sequential digestion of the labeled enzyme with trypsin, chymotrypsin, and endoproteinase Glu-C yielded a modified and radiolabeled decapeptide. When compared with the reported primary amino acid sequence of protein methylase II from rat brain, the amino acid composition of the decapeptide matched residues 113-121. This segment forms the midpoint region of the enzyme (234 amino acid residues). An important characteristic of the sequence is the presence of two adjacent aspartic acid residues (Asp117-Asp118) which most likely provide the negative charge environment for the sulfonium moiety of the AdoMet molecule. PMID- 8443167 TI - Wheat germ and yeast RNA polymerase II: photoaffinity labeling by 4-thiouracil 5' monophosphate positioned uniquely at the 3' end of an enzyme-bound [32P] containing transcript. AB - A stable ternary transcription complex was formed with either wheat germ or yeast RNA polymerase II using a ribotrinucleotide primer (GpCpG) to initiate transcription on a short synthetic single-strand DNA template. The template was designed to limit the incorporation of a photoprobe S4-UMP (4-thio-UMP) to a unique position at the 3' terminus of the transcript. The resulting stable ternary transcription complex was photolyzed to cross-link the bound transcript ([32P]-labeled by the incorporation of [alpha-32P]CMP) with the protein domain at or near the active site. Separation of the protein components by electrophoresis in polyacrylamide gel containing SDS and analysis by autoradiography and silver staining revealed that for either enzyme only the largest subunit was [32P] labeled. PMID- 8443168 TI - Extensive heterogeneity of proteoglycans bearing fucose-branched chondroitin sulfate extracted from the connective tissue of sea cucumber. AB - The major sulfated polysaccharide in the sea cucumber body wall is a fucose branched chondroitin sulfate. This glycosaminoglycan has side-chain disaccharide units of sulfated fucopyranosyl or sulfate esters linked to the O-3 position of the beta-D-glucuronic acid residues. These unusual fucose branches and sulfate esters block the access of chondroitinases to the chondroitin sulfate core [Vieira & Mourao (1988) J. Biol. Chem. 263, 18176-18183; Vieira et al. (1991) J. Biol. Chem. 266, 13530-13536]. We now report the isolation and preliminary characterization of the proteoglycans bearing this unique fucose-branched chondroitin sulfate. They were extracted using guanidine hydrochloride solutions containing protease inhibitors and were purified by anion-exchange and gel filtration columns. Interestingly, the sea cucumber proteoglycans were cleaved by chondroitinase AC or ABC, indicating that the beta-D-glucuronic acid residues close to the reducing end of the polysaccharide chain are neither fucosylated nor sulfated. SDS-polyacrylamide gel electrophoresis revealed several fractions of proteoglycans of different molecular sizes but containing a similar hexuronic acid/protein ratio and a similar type of glycan chain. Possibly, the low molecular-size fractions arise from a protease cleavage of a larger molecule. In contrast with the results observed for most vertebrate proteoglycans, which contain a single core protein for each type of proteoglycan, chondroitinase AC or ABC releases from the sea cucumber proteoglycans a wide variety of core proteins. These observations are the first detailed study of a proteoglycan from invertebrate tissue and reveal extensive heterogeneity when compared with proteoglycans from vertebrate connective tissue. PMID- 8443169 TI - Static and time-resolved absorption spectroscopy of the bacteriorhodopsin mutant Tyr-185-->Phe: evidence for an equilibrium between bR570 and an O-like species. AB - The light-dark adaptation, photocycle kinetics, and acid-induced blue formation of the bacteriorhodopsin (bR) mutant Tyr-185-->Phe (Y185F) expressed in Halobacterium halobium have been investigated by both static and time-resolved visible absorption spectroscopy. Evidence is presented that a pH-dependent equilibrium exists between a bR570-like form (bRY185F570) and a red-shifted species in the light-adapted form of Y185F. In two related papers, we show that this species has vibrational features similar to the O intermediate. Key findings are that light adaptation causes formation of a purple species similar to bR570 and a second long-lived red-shifted species with a lambda max near 630 nm, well above the pH for the acid-induced blue transition. The concentration of the red shifted species is pH- and salt-dependent, decreasing reversibly at high pH and high ionic strength. The dark-adapted state of Y185F also contains a small amount of the red-shifted species which is reversibly titratable. Dark adaptation is much slower than wild-type bR and causes a parallel decay of light-adapted bR and the red-shifted species. Time-resolved visible absorption spectroscopy reveals that the purple and the red-shifted species undergo separate photocycles. The purple species exhibits a relatively normal photocycle except for an increased rate of M formation kinetics. The red-shifted species has a photocycle involving a red-shifted K intermediate and a second longer lived intermediate possibly similar to N. The apparent absence of an O intermediate in the late photocycle of Y185F is attributed to cancellation by depletion bands due to the photoreacting red-shifted species.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8443170 TI - Fourier transform Raman spectroscopy of the bacteriorhodopsin mutant Tyr-185- >Phe: formation of a stable O-like species during light adaptation and detection of its transient N-like photoproduct. AB - Near-infrared FT-Raman spectroscopy can be used to measure the vibrations of the bacteriorhodopsin (bR) chromophore without the disadvantage of conventional visible resonance Raman spectroscopy, where the visible excitation drives the bR photoreactions. We utilized this technique to investigate the light-dark adaptation of bacteriorhodopsin and the mutant Tyr-185-->Phe (Y185F) at room temperature in solution. Compared to wild-type bR, both the FT-Raman and resonance Raman spectra of the light-adapted Y185F displayed new features characteristic of the vibrations of the O intermediate. Light adaptation of Y185F was found to involve a 13-cis, C=N syn-->all-trans isomerization of the retinal chromophore which produces a species similar to bR570 and a second O-like species. Dark adaptation, which was much slower in Y185F compared to wild-type bR, involved a parallel decay of the bR570 and O-like species and resulted in a decreased all-trans:13-cis ratio compared to wild type. Further evidence for the existence of an O-like species in Y185F comes from pump-probe Raman difference spectroscopy, where a red pump beam is found to produce a species very similar to the N intermediate in the photocycle. This species is shown by stroboscopic Raman measurements to exist transiently even at high pH. We postulate that when the Y185F chromophore has an all-trans structure the effective pKa of Asp-85 and Asp 212 is elevated in Y185F due to the disruption of the Asp-212/Tyr-185 hydrogen bond, thereby accounting for the increased protonation of these residues in the O like species. PMID- 8443171 TI - FTIR difference spectroscopy of the bacteriorhodopsin mutant Tyr-185-->Phe: detection of a stable O-like species and characterization of its photocycle at low temperature. AB - Fourier transform infrared difference spectroscopy has been used to study the photocycle of the mutant Tyr-185-->Phe expressed in native Halobacterium halobium and isolated as intact purple membrane fragments. We find several changes in the low-temperature bR-->K, bR-->L, and bR-->M FTIR difference spectra of Y185F relative to wild-type bR which are not directly related to the absorption bands associated with Tyr-185. We show that these features arise from the photoreaction of a stable red-shifted species (OY185F) with a vibrational spectrum similar to the O intermediate. By using photoselection and FTIR spectroscopy, we have been able to characterize the photoproducts of this OY185F species. A K-like photoproduct is formed at 80 K which has a 13-cis structure. However, it differs from K630, exhibiting an intense band at 990 cm-1 most likely due to a hydrogen out-of-plane vibrational mode of the chromophore. At 170 and 250 K, photoexcitation of OY185F produces an intermediate with vibrational features similar to the N intermediate in the wild-type bR photocycle. However, no evidence for an M-like intermediate is found. Although Asp-96 undergoes a change in its environment/protonation state during the OY185F photocycle, no protonation changes involving Asp-85 and Asp-212 were detected. These results provide strong evidence that light adaptation of Y185F produces two species similar to bR570 and the O intermediate. Differences in their respective photocycles can be explained on the basis of differences in the protonation states of the residues Asp-85 and Asp-212 which are ionized in bR570 and undergo net protonation upon OY185F formation. PMID- 8443172 TI - Molecular dynamics study of the proton pump cycle of bacteriorhodopsin. AB - Retinal isomerization reactions, which are functionally important in the proton pump cycle of bacteriorhodopsin, were studied by molecular dynamics simulations performed on the complete protein. Retinal isomerizations were simulated in situ to account for the effects of the retinal-protein interactions. The protein structure employed was that described in Nonella et al. [Nonella, M., Windemuth, A., & Schulten, K. (1991) Photochem. Photobiol. 54, 937-948]. We investigated two mechanisms suggested previously for the proton pump cycle, the 13-cis isomerization model (C-T model) and the 13,14-dicis isomerization model. According to these models, retinal undergoes an all-trans-->13-cis or an all trans-->13,14-dicis photoisomerization as the primary step of the pump cycle. From the simulations emerged a consistent picture of isomerization reactions and their control through the retinal-protein interactions which favors the 13,14 dicis isomerization model. Electrostatic interactions between the protonated Schiff base and its counterion are found to direct the stereochemistry of retinal in the photocycle: this and other interactions steer retinal toward the 13,14 dicis geometry in the primary photoreaction, toward the 13-cis geometry after its deprotonation, and to the all-trans isomeric form after its reprotonation. We also propose a catalytic mechanism involving hydrogen bonding of the Schiff base to main chain oxygen atoms of Val-49 and Thr-89 for the 13-cis-->all-trans thermal reisomerization of retinal. The all-trans-->13-cis primary photoreaction required by the "C-T" model was found to be inhibited by the Schiff base counterion interaction, but the possibility of such a reaction can not be excluded. In order to investigate the "C-T" model, we enforced an all-trans-->13 cis photoisomerization in a simulation and monitored the subsequent protein conformational changes. The effects of internal water molecules on retinal isomerization reactions were studied by placing 16 water molecules in the proton conduction channel. The results indicate that water affects the nature of the Schiff base counterion and the nature of the primary photoreaction. Water chains, formed between positively and negatively charged protein groups in the proton conduction channel, are suggested to be involved in the reprotonation and deprotonation of retinal. PMID- 8443173 TI - Characterization of the smooth muscle calponin and calmodulin complex. AB - Calponin interacts with several Ca2+ binding proteins in a Ca(2+)-dependent manner. In order to determine the possible biological relevance of these interactions in smooth muscle function, it is necessary to characterize the strength and stoichiometry of the complexes formed. The interaction between calponin and calmodulin can be monitored through an acrylodan label on a cysteine of calponin. The fluorescently labeled calponin possesses the same biological function and physical behavior in binding to calmodulin as the native calponin. This probe is very environment-sensitive and responds to the calponin-calmodulin interaction by the emission peak blue-shifting 20 nm and by the fluorescent quantum yield increasing 3.5 times at 460 nm. The stoichiometric nature of this complex has been determined using analytical ultracentrifugation and is two calmodulins to one calponin, and the interaction is Ca(2+)-sensitive with a Kd1 of < or = 0.22 microM and a Kd2 of 2.5-3.4 microM. Calmodulin is not the only protein which interacts with calponin in this manner, but rather this interaction seems to be a general feature attributable to all hydrophobic patch exposing proteins, suggesting that it may be nonspecific, occurring because of a generalized mode of interaction. Two other proteins, S-100b from bovine brain and SMCaBP-11 from smooth muscle, had stronger affinities for calponin, and in particular interaction of SMCaBP-11 with calponin may be biologically relevant. In determining the nature of calponin's interaction with these Ca2+ binding proteins, it was apparent there was no effect of Ca2+ upon calponin itself and physical studies could find no evidence that calponin interacts with calcium. PMID- 8443174 TI - Effect of the B ring and the C-7 substituent on the kinetics of colchicinoid tubulin associations. AB - The kinetics of four B-ring derivatives of colchicine binding to tubulin has been examined quantitatively. The bindings of deacetamidocolchicine, deacetylcolchicine, demecolcine, and N-methyl-demecolcine to tubulin were biphasic processes. The association rate constants were determined as a function of temperature, and the thermodynamic parameters for the transition states of the fast phase were calculated. The kinetic parameters for the formation of the deacetylcolchicine-tubulin, demecolcine-tubulin, and N-methyldemecolcine-tubulin complexes were very similar to each other, but different from the parameters for the colchicine-tubulin association. In particular, the global activation enthalpies for the formation of the three aminocolchicinoid-tubulin complexes were 3-5 kcal/mol greater than the global activation enthalpy of colchicine binding to tubulin. These results indicate that electronic rather than steric properties of the B-ring substituent are of greater importance in the activation enthalpy of colchicinoids binding to tubulin. In contrast, the global activation enthalpy for deacetamidocolchicine, which lacks a substituent on the C-7 carbon, binding to tubulin was virtually identical to the global activation enthalpy previously found for the colchicine analog that lacks the B ring, 2-methoxy-5 (2,3,4-trimethoxyphenyl)tropone, binding to tubulin (Bane, S., Puett, D., Macdonald, T. L., & Williams, R. C., Jr. (1984) J. Biol. Chem. 259, 7391-7398). This result demonstrates that the carbons of the B ring are not involved in the transition state for the formation of colchicinoid-tubulin complexes. The first order dissociation rate constants of the colchicinoid-tubulin complexes were determined at 37 degrees C. The dissociation profiles of the colchicinoid-tubulin complexes also consisted of two phases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8443175 TI - Translocation of spin-labeled phospholipids through plasma membrane during thrombin- and ionophore A23187-induced platelet activation. AB - After incorporation of spin-labeled phosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine analogues in the outer leaflet of the plasma membrane in resting platelets, more than 90% amino-head analogues accumulated within 30 min in the inner leaflet by aminophospholipid translocase activity, while choline analogues mostly remained on the outer leaflet. Platelets were then activated by thrombin or Ca2+ ionophore A23187. No outward movement of internally located spin labeled aminophospholipids was observed during thrombin-induced activation, whereas the influx of externally located probes increased slightly. During A23187 mediated activation, similar slightly increased influx was observed, while 40-50% of the initially internally located aminophospholipids could then be extracted from the outer leaflet. This sudden exposure on the outer face was dependent on an increase in intracellular Ca2+ and achieved in less than 2 min at 37 degrees C. Inhibition of translocase activity by N-ethylmaleimide did not induce any aminophospholipid outflux. When probes were incorporated on the outer face of the plasma membrane in resting platelets, they were still fully accessible from the extracellular medium after A23187-induced activation. Moreover, they were distributed between the vesicles and remnant platelets in proportion to the external membrane phospholipidic content in each structure. This suggested that no scrambling of plasma membrane leaflets occurred during the vesicle blebbing. Moreover, the spin-labeled aminophospholipids exposure rate and amplitude were unchanged when vesicle formation was inhibited by the calpain inhibitor calpeptin. These results indicate that loss of asymmetry thus inducing generation of a catalytic surface is not the consequence of vesicle formation. Conversely, we propose that vesicle shedding is an effect of PL transverse redistribution and calpain-mediated proteolysis during activation. PMID- 8443176 TI - Insulin binding to rat liver membranes predicts a homogeneous class of binding sites in different affinity states that may be related to a regulator of insulin binding. AB - Insulin binding to pericanicular, liver plasma membranes was measured at equilibrium as a function of temperature from 4 degrees C to 37 degrees C. Scatchard plots of the binding data obtained at temperatures from 4 degrees C to 15 degrees C were linear and the Hill plots were characterized by Hill coefficients equal to unity. Thus, insulin binding under these conditions was consistent with the presence of a single class of homogeneous, noninteracting binding sites. However, the Scatchard plots of binding data obtained above 15 degrees C were curvilinear, and the Hill coefficients derived from these data were about 0.75. This apparent change in the complexity of the binding with increasing temperature was not due to gross ligand or receptor degradation and care was taken to ensure that all assumptions inherent in interpreting the equilibrium binding data were valid. Changes in membrane fluidity or the presence of a cryptic population of receptors which surface with increasing temperature also could not account for this apparent increase in the complexity of the binding above 15 degrees C because identical observations were made using nonionic and ionic detergent-solubilized liver plasma membranes. Thus, we were able to rule out heterogeneity of binding sites as a model to explain the increased complexities of the binding above 15 degrees C. We conclude that the temperature dependence of insulin binding in impure but intact receptor preparations is consistent with a two-state model of the insulin receptor. Using this model, we predict that one conformational state of the insulin receptor exists below 15 degrees C but that two affinity states of the receptor exists at higher and physiological temperature.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8443177 TI - Spectroscopic and functional characterization of the putative transmembrane segment of the minK potassium channel. AB - MinK (Isk) is a voltage-dependent K+ channel whose gene has been recently cloned and which consists of 130 amino acids [Takumi, T., Ohkubo, H., & Nakanishi, S. (1988) Science 242, 1042-1045]. The protein contains one putative transmembrane segment by hydropathy analysis. Whether this putative transmembrane segment is involved in the function of the protein was studied. A 32 amino acid peptide (residues 41-72) with the sequence SKLEALYILMVLGFFGFFTLGIMLSYIRSKKL, containing the hypothesized transmembrane domain, designed TM-minK, was synthesized and fluorescently labeled. The alpha-helical content of TM-minK, assessed in methanol using circular dichroism (CD), was 57%. The fluorescent emission spectrum of 7 nitrobenz-2-oxa-1,3-diazol-4-yl (NBD)-labeled TM-minK displayed a blue shift upon binding to small unilamellar vesicles (SUV), reflecting a relocation of the fluorescent probe to an environment of increased apolarity, i.e., within the lipid bilayer. The increase in NBD's fluorescence upon mixing NBD-labeled TM-minK with small unilamellar vesicles (SUV) was used to generate a binding isotherm, from which was derived a surface partition coefficient of 5.5 x 10(4) M-1. Fluorescence energy transfer measurements between carboxyfluoresceine-labeled and rhodamine-labeled analogues suggest that TM-minK aggregates within membranes. In addition, single-channel experiments revealed that TM-minK can form single channels in planar lipid membranes only when a trans negative potential is applied. The findings herein experimentally support a role of the transmembrane segment of minK both in the assembly and as a constituent of the pore formed by the protein. PMID- 8443178 TI - Inhibitors of the isoprenylated protein endoprotease. AB - The isoprenylation pathway requires an endoprotease that cleaves the modified protein at the isoprenylated cysteine residue. This endoprotease was readily assayed with simple tetrapeptide substrates of the type N-acetyl-S-farnesyl-L-Cys (AFC)-Val-Ile-Met, where AFC and the tripeptide are the products of the hydrolysis. The endoprotease proved to be unaffected by (1) serine protease inhibitors, including (4-amidinophenyl)methanesulfonyl fluoride, aprotinin, and leupeptin, by (2) cysteine protease inhibitors, including E-64 and leupeptin [the enzyme is, however, inhibited by p-(hydroxymercuri)benzoate], by (3) metalloprotease inhibitors, including phosphoramidon, EDTA, and 1,10 phenanthroline, or by (4) the aspartyl protease inhibitor pepstatin. The conclusion from these data is that the enzyme is probably not a metalloenzyme. N Boc-S-all-trans-farnesyl-L-cysteine (BFC) derivatives containing a statine moiety are also not inhibitory, strongly suggesting that the enzyme is not an aspartyl protease. However, the enzyme is potently inhibited by the aldehyde derivative of BFC (K1 = 1.9 microM), which is consistent with the idea that the enzyme is a serine or cysteine protease. Potent tetrapeptide-based competitive inhibitors were prepared. Analogs with the scissile bond modified so that hydrolysis could not occur were excellent inhibitors. An analog containing BFC-statine-Val-Ile-Met inhibited the endoprotease with a K1 = 64 nM. The equivalent pseudopeptide psi (CH2-NH) analog was almost as potent, indicating that the statine moiety simply represents a nonhydrolyzable linker. PMID- 8443179 TI - Cation binding and conformation of tryptic fragments of Nereis sarcoplasmic calcium-binding protein: calcium-induced homo- and heterodimerization. AB - Nereis sarcoplasmic calcium-binding protein (NSCP) is a compact 20-kDa protein that competitively binds three Ca2+ or Mg2+ ions and displays strong positive cooperativity. Its three-dimensional structure is known. It thus constitutes a good model for the study of intramolecular information transduction. Here we probed its domain structure and interaction between domains using fragments obtained by controlled proteolysis. The metal-free form, but not the Ca2+ or Mg2+ form, is sensitive to trypsin proteolysis and is preferentially cleaved at two peptide bonds in the middle of the protein. The N-terminal fragment 1-80 (T1-80) and the C-terminal fragment 90-174 (T90-174) were purified to electrophoretic homogeneity. T1-80, which consists of a paired EF-hand domain, binds one Ca2+ with Ka = 3.1 x 10(5) M-1; entropy increase is the main driving force of complex formation. Circular dichroism indicates that T1-80 is rich in secondary structure, irrespective of the Ca2+ saturation. Ca2+ binding provokes a difference spectrum which is similar to that observed in the intact protein. These data suggest that this N-terminal domain constitutes the stable structural nucleus in NSCP to which the first Ca2+ binds. T90-174 binds two Ca2+ ions with Ka = 3.2 x 10(4) M-1; the enthalpy change contributes predominantly to the binding process. Metal-free T90-174 is mostly in random coil but converts to an alpha-helical-rich conformation upon Ca2+ binding. Ca2+ binding to T1-80 provokes a red-shift and intensity decrease of the Trp fluorescence but a blue-shift and intensity increase in T90-174.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8443180 TI - Synthesis and characterization of fluorescently labeled bovine brain G protein subunits. AB - G proteins play an important role in transmitting hormonal signals, and fluorescence techniques would be useful to study their cellular distribution and mechanisms. To prepare active fluorescent G protein Go/Gi or beta gamma subunits were reacted with fluorescein isothiocyanate (FITC) to label the alpha (F-alpha) and gamma (F-gamma/beta) subunits or with (iodoacetamido)tetramethylrhodamine (TMR-IAA) to label the beta subunit (TMR-beta gamma). Unreacted dye was removed from the labeled proteins by ultrafiltration, followed by further purification using HPLC gel filtration. The molar ratios of dye to protein were 0.96 +/- 0.15, 0.59 +/- 0.07, and 1.37 +/- 0.09 for labeled alpha,beta, and gamma subunits, respectively. GTP gamma S binding to F-alpha and ADP-ribosylation by pertussis toxin of F-alpha were reduced to 63% and 78% of control, respectively. F-alpha was a heterogeneous population of alpha subunits. Active F-alpha containing less than one (0.7) label/subunit (F-alpha-Mono Q) was separated from unlabeled and multiply labeled F-alpha by Mono Q anion-exchange chromatography. F-alpha-Mono Q displayed reduced GTPase activity (turnover number was 46% of control), while GTP gamma S binding and ADP-ribosylation by pertussis toxin were only decreased to 78% and 82% of control, respectively. TMR-beta gamma and F-gamma/beta retain full function compared to native beta gamma, as measured by three methods: (1) TMR beta gamma and F-gamma/beta are able to form heterotrimers with alpha o subunits, (2) TMR-beta gamma and F-gamma/beta support the ADP ribosylation of alpha o subunits by pertussis toxin, and (3) TMR-beta gamma and F-gamma/beta inhibit forskolin-stimulated adenylyl cyclase activity. The fluorescent G protein subunits will be valuable tools to study G protein mechanisms in reconstituted membranes and intact cells. PMID- 8443181 TI - Interaction of 7-bromoacetyl-7-desacetylforskolin, and alkylating derivative of forskolin, with bovine brain adenylyl cyclase and human erythrocyte glucose transporter. AB - 7-Bromoacetyl-7-desacetylforskolin (BrAcFsk), an alkylating derivative of forskolin, activated adenylyl cyclase and irreversibly blocked high affinity forskolin binding sites in human platelet membranes and rat brain membranes (Laurenza et al., 1990). Photoincorporation of an iodinated arylazido derivative of forskolin, 125I-6-AIPP-Fsk, into adenylyl cyclase in bovine brain membranes was irreversibly inhibited by BrAcFsk but not by 1,9-dideoxy-BrAcFsk, suggesting that BrAcFsk was reacting specifically with a nucleophilic group(s) at the forskolin binding site of adenylyl cyclase. Immunoblotting with antiforskolin antiserum demonstrated that partially purified bovine brain adenylyl cyclase had incorporated BrAcFsk. The interaction of BrAcFsk with the glucose transporter in human erythrocyte membranes was examined in a similar manner. Photoincorporation of 125I-7-AIPP-Fsk, an iodinated arylazido derivative of forskolin which is specific for the glucose transporter, into the glucose transporter was not irreversibly inhibited by BrAcFsk, suggesting that, in contrast to adenylyl cyclase, there is no reactive nucleophilic group at the forskolin binding site on the human erythrocyte glucose transporter. The immunoblotting procedure with antiforskolin antiserum confirmed that BrAcFsk was not covalently attached to human erythrocyte glucose transporter. PMID- 8443182 TI - Alignment of disulfide bonds of the extracellular domain of the interferon gamma receptor and investigation of their role in biological activity. AB - The extracellular ligand binding domain of the human interferon gamma receptor includes eight cysteine residues forming four disulfide bonds. Only the nonreduced protein binds interferon gamma. We investigated the alignment of the disulfide bonds, using an enzymatically deglycosylated form of a soluble interferon gamma receptor, produced in baculovirus-infected insect cells. The soluble receptor was digested with endoproteinase Glu-C and proteinase K, and the proteolytic fragments were characterized by amino acid sequence analysis and mass spectrometry. It was found that four consecutive disulfide bonds are formed between residues Cys60-Cys68, Cys105-Cys150, Cys178-Cys183, and Cys197-Cys218. We also investigated the role of the disulfide bonds in biological activity of the receptor, using site-directed mutagenesis and by exchanging the cysteine residues for serines. The mutated proteins were expressed in Escherichia coli and analyzed for ligand binding capacity on protein blots. The assays showed that all disulfide bonds are essential for full ligand binding capacity. Double or quadruple mutations at cysteine residues 60 and 68, and residues 178, 183, 197, and 218, respectively, resulted in complete loss of the activity, whereas double mutations at residues 105 and 150, 178 and 183, and 197 and 218, respectively, resulted in a residual activity about 1 order of magnitude lower than that of the wild type. The specific antibodies gamma R38 and gamma R99 detected conformational epitopes stabilized by disulfide bonds involving cysteine residues 60 and 68, and 178 and 183, respectively. PMID- 8443183 TI - Disulfide bonds in recombinant human platelet-derived growth factor BB dimer: characterization of intermolecular and intramolecular disulfide linkages. AB - Interchain cystines of PDGF-BB dimer were characterized by Edman reaction and by SDS-PAGE analysis on the protein which was chemically cleaved at Trp-40. It was found that Cys-43 has a key role in dimer formation, asymmetrically cross-linked to a cysteine residue of another identical subunit. The remaining cystines participate in the intramolecular disulfide linkages. Pepsin digestion of PDGF-BB dimer generated several small peptides and one ubiquitous Cys-containing peptide. Sequence analyses of several Cys-containing peptides indicated the existence of three intramolecular disulfide linkages including Cys-16--Cys-60, Cys-49--Cys-97, and Cys-53--Cys-99. Two interchain disulfide bonds of Cys-43--Cys-52 between two subunits were deduced from the partial reduction and alkylation of PDGF-BB. This study provides chemically determined disulfide linkages of PDGF-BB. PMID- 8443184 TI - Lipid headgroup and acyl chain composition modulate the MI-MII equilibrium of rhodopsin in recombinant membranes. AB - A current paradigm for visual function centers on the metarhodopsin I (MI) to metarhodopsin II (MII) conformational transition as the trigger for an intracellular enzyme cascade leading to excitation of the retinal rod. We investigated the influences of the membrane lipid composition on this key triggering event in visual signal transduction using flash photolysis techniques. Bovine rhodopsin was combined with various phospholipids to form membrane recombinants in which the lipid acyl chain composition was held constant at that of egg phosphatidylcholine (PC), while the identity of the lipid headgroups was varied. The ratio of MII/MI produced in these recombinants by an actinic flash at 28 degrees C was studied as a function of pH. The results were compared to the photochemical function observed for rhodopsin in native retinal rod outer segment (ROS) membranes, in total native ROS lipid recombinants, and in dimyristoylphosphatidylcholine (DMPC) recombinants. In membrane recombinants incorporating lipids derived from egg PC, as well as in the total ROS lipids control and the native ROS disk membranes, MI and MII were found to coexist in a pH-dependent, acid-base equilibrium on the millisecond time scale. The recombinants of rhodopsin with egg PC, either alone or in combination with egg PC derived phosphatidylethanolamine (PE) or phosphatidylserine (PS), exhibited substantially reduced photochemical activity at pH 7.0. However, all recombinants comprising phospholipids with unsaturated acyl chains were capable of full native like MII production at pH 5.0, confirming previous results [Gibson, N.J.. & Brown, M.F. (1990) Biochem. Biophys. Res. Commun. 169, 1028-1034]. It follows that energetic constraints on the MI and MII states imposed by egg PC-derived acyl chains can be offset by increased activity of H+ ions. The data reveal that the major effect of the membrane lipid composition is to alter the apparent pK for the MI-MII conformational equilibrium of rhodopsin [Gibson, N.J., & Brown, M.F. (1991) Biochem. Biophys. Res. Commun. 176, 915-921]. Recombinants containing only phosphocholine headgroups exhibited the lowest apparent pK values, whereas the presence of either 50 mol % PE or 15 mol % PS increased the apparent pK. The inability to obtain full native-like function in recombinants having egg PC derived chains and a native-like headgroup composition indicates a significant role of the polyunsaturated docosahexaenoic acid (DHA) chains (22:6 omega 3) of the native retinal rod membrane lipids. Temperature studies of the MI-MII transition enabled an investigation of lipid influences on the thermodynamic parameters of a membrane protein conformational change linked directly to function.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8443185 TI - Hemostatic failures and heart-lung transplantation: assessing the current situation. PMID- 8443186 TI - Transfusion in transplant patients: the good, the bad, and the ugly. AB - Several transfusion-related complications have particular relevance to the transplant setting. Transfusions reportedly improve solid organ graft survival, especially when the donor and recipient share at least one HLA-DR antigen. Whereas the mechanism for this effect is unclear, less favorable "immunomodulating" effects of transfusion may increase postoperative infections and shorten survival time and disease-free intervals in patients with a variety of malignancies who are undergoing surgery. The contribution of the different components of the blood transfusion to these outcomes remains speculative. Directed donations, especially from relatives and in the setting of a recipient who is immunosuppressed, may give rise to a severe but under-appreciated immunologic consequence of transfusion: graft-versus-host disease. Although still rarely reported, transfusional graft-versus-host disease is almost invariably fatal. This complication is entirely avoidable if the transfused blood product is appropriately gamma-irradiated. Infectious complications remain the most feared consequence of transfusion; the cytomegalovirus, the human immunodeficiency virus, and hepatitis B and C may run a more fulminant course in transplant patients who are immunosuppressed. Red cell substitutes, hematopoietic growth factors, and autologous transfusion are among the strategies for preventing complications of blood transfusion. With the advent of cyclosporine and more potent and specific immunosuppressive therapies, the desirability of preoperative transfusion for organ grafts warrants reevaluation. PMID- 8443187 TI - Coronary artery disease in patients with hearts from older donors: morphologic features and therapeutic implications. AB - Of 558 heart transplant recipients, 234 long-term survivors (more than 12 months) were studied by annual catheterization to evaluate the risk of postoperative coronary artery disease in hearts from older donors. No significant difference was found in graft function between hearts from younger and older donors (group I: n = 157, mean donor age 23 +/- 5 years, mean follow-up 45 +/- 22 months; group II: n = 77, mean donor age 43 +/- 5 years, mean follow-up 42 +/- 22 months) as indicated by left and right ventricular ejection fraction, pulmonary artery pressure, and pulmonary capillary wedge pressure. Two morphologic patterns of coronary artery disease were observed: a diffuse type of concentric narrowing of the arteries (type 1) and a focal type with proximal single-vessel stenosis (type 2). Type 1 occurred in eight patients (5%) in group I and in four patients in group II (5%) (p = not significant). Type 1 coronary artery disease led to graft failure in seven patients in group I and two patients in group II. Type 2 coronary artery disease occurred in seven patients (4%) in group I and in 14 (18%) in group II (p < 0.001). No death was related to graft failure in patients with type 2 coronary artery disease. Eight patients with type 2 coronary artery disease were successfully treated by percutaneous transluminal coronary angioplasty; one patient underwent coronary artery bypass grafting. Hearts from older donors provide normal graft function. The risk of diffuse coronary artery disease is not elevated in comparison to hearts from younger donors. The higher incidence of focal coronary artery disease suggests donor-transmitted disease that can successfully be treated by conventional therapy. PMID- 8443188 TI - Lack of association between endomyocardial evidence of rejection in the first six months and the later development of transplant-related coronary artery disease. AB - The development of transplant-related coronary artery disease (TCAD) is the major determinant of long-term heart transplant survival. To test the hypothesis that TCAD might be related to cellular myocardial rejection, the grades of rejection seen at all biopsies performed in the first 6 months after heart transplantation were analyzed in 108 patients who survived more than 6 months. The development of TCAD was assessed at routine follow-up coronary angiography in 101 patients and at necropsy in seven patients. This data was analyzed with Kaplan-Meier survival curves and Cox proportional hazard regression analysis. No significant association was found between either moderate rejection or any level of rejection and the later development of TCAD, nor did the absence of any rejection protect against its development. PMID- 8443189 TI - Chronic rejection in rat aortic allografts. IV. Effect of hypercholesterolemia in allograft arteriosclerosis. AB - Rat aortic allografts transplanted across histoincompatible strains develop arteriosclerotic alterations in the vascular wall that are virtually indistinguishable from those observed in human heart allografts during chronic rejection. In this study we have investigated whether hypercholesterolemia in the recipient rat accelerates allograft arteriosclerosis. Hypercholesterolemia was induced by a 4% cholesterol and 0.5% cholic acid diet, added to the normal rat diet. The cholesterol and cholic acid diet increased the level of serum total cholesterol from 1.3 +/- 0.0 to 4.8 +/- 0.9 (+/- SD) mmol/L and the level of low density lipoprotein cholesterol from 0.3 +/- 0.0 to 2.6 +/- 1.0 mmol/L (p < 0.05) but caused no change in the level of high-density lipoprotein cholesterol, 1.0 +/ 0.1 versus 0.7 +/- 0.3 mmol/L. The level of plasma triglycerides remained also unchanged. Quantitation of two major chronic rejection-associated eicosanoids from the allograft vascular wall showed a significant increase in the synthesis of thromboxane B2 in the hyperlipidemic animals from 6.0 +/- 5.0 to 8.0 +/- 5.0 ng/mg dry weight and a slight reduction in the synthesis of 6-keto-prostaglandins F1 alpha. In vivo labeling of the recipient rat with tritiated thymidine and autoradiography showed that hypercholesterolemia did not affect the proliferation of inflammatory cells in the allograft adventitia, slightly increased the proliferation of smooth muscle cells in the media from 23 +/- 14 cells to 34 +/- 13 cells (+/- SEM) per cross section (p = ns), but slightly reduced the proliferation of smooth muscle cells in the intima from 13 +/- 6 to 6.2 +/- 1.5 (p = ns). Hypercholesterolemic recipients did not show any significant enhancement but, in fact, showed a delay in the generation of arteriosclerotic changes in the allograft intima. We conclude that although hypercholesterolemia, in the absence of hypertriglyceridemia, induces significant alterations in the eicosanoid metabolism and minor alterations in smooth muscle cell proliferation in the transplant vascular wall, it does not enhance arteriosclerotic alterations in chronically rejecting rat aortic allografts. PMID- 8443191 TI - Inhibition of the pyrimidine biosynthetic pathway with S-8660, an analogue of brequinar sodium, prolongs cardiac allograft survival in rats. AB - The compound S-8660 is a member of a family of antiproliferative drugs that act on de novo pyrimidine synthesis through selective inhibition of the mitochondrial enzyme dihydroorotate dehydrogenase. S-8660 is highly effective in preventing the development of delayed-type hypersensitivity in mice and in suppressing human mixed-lymphocyte responses. We have tested its ability to prevent cardiac allograft rejection in the ACI (RT1a) to Lewis (RT1(1)) rat strain combination, based on the immunosuppressive activity of this compound and its similarity to another member of this group, brequinar sodium. Daily oral administration of the drug (5 to 20 mg/kg) was begun 2 days before transplantation and extended for periods of time up to 30 days after graft placement. Control grafts were promptly rejected (median survival time, 7.0 +/- 0.5 days). Administration of S-8660 was effective in extending graft survival in a dose-dependent fashion. The efficacy of S-8660 could be improved with a high initial concentration of the drug, followed by a reduction ("tapering") in the level of drug administration (median survival time, 32.0 +/- 4.6 days) or by use in combination with cyclosporine. The differences in the mode of action of S-8660, when compared to cyclosporine or FK 506, suggest that the disruption of de novo pyrimidine synthesis may be an effective and safe addition to a polytherapeutic approach for the prevention of allograft rejection in clinical transplantation. PMID- 8443190 TI - Use of theophylline for treatment of prolonged sinus node dysfunction in human orthotopic heart transplantation. AB - Sinus node dysfunction may complicate heart transplantation in over 50% of cases, leading to prolonged bradyarrhythmias in 20% of recipients. Permanent pacemaker implantation, the standard treatment for such persistent rhythm disturbances, can result in significant complications in this setting. A protocol with theophylline, a methylxanthine known to reverse the sinus node electrophysiologic abnormalities observed in transplant patients, was initiated at our institution in October 1989 to treat posttransplantation bradyarrhythmias and to reduce the need for pacemaker implantation. Patients with sinus or nodal bradycardia or sinus arrest were given theophylline orally; the drug was initiated in 15 of 38 patients (39.5%), 3 to 24 days after transplantation. Mean duration of treatment was 57.4 days (range, 20 to 105 days). Normal sinus rhythm with a rate of more than 90 beats/min was restored in 14 of 15 patients (93.3%). Permanent pacing was required in one patient. Transplant recipients before October 1989 (group 1, n = 112) were compared with subsequent transplant recipients (group 2, n = 38). These groups did not differ significantly in incidence of bradyarrhythmias or potential risk factors for posttransplantation sinus node dysfunction, though a greater preoperative use of amiodarone occurred in group 2. Permanent pacemaker requirement was significantly reduced from 16.1% in group 1 to 2.6% in group 2 (p < 0.05) with the introduction of theophylline. Theophylline is effective treatment for posttransplantation bradyarrhythmias, thereby resulting in a reduced need for pacemaker implantation. PMID- 8443192 TI - Laparoscopic cholecystectomy in heart transplant recipients. AB - To our knowledge these are the first three cases of laparoscopic cholecystectomy in heart transplant recipients. In one case the procedure was performed in the early posttransplant period. All three patients had uneventful postoperative outcomes and early hospital discharge. Laparoscopic cholecystectomy may be a safe alternative for elective cholecystectomy in heart transplant recipients. PMID- 8443193 TI - Explantation, repair, and reimplantation of the heart for left ventricular rupture after mitral valve replacement. AB - Rupture of the posterior wall of the left ventricle is a rare but often fatal complication after mitral valve replacement. A method of repair is given that, although unsuccessful in its final outcome, may represent a worthwhile alternative surgical technique. PMID- 8443194 TI - Research use of the artificial heart. PMID- 8443195 TI - Recurrent giant cell myocarditis after transplantation. PMID- 8443196 TI - Early pulmonary vein thrombosis after single lung transplantation. AB - Pulmonary venous obstruction after single lung transplantation may be mistaken for reperfusion injury or myocardial dysfunction. Complete obstruction of one of the major pulmonary veins will result in hemorrhagic infarction of the affected lobe within 4 to 6 hours, limiting the option of treatment to resection (lobectomy) or retransplantation. Early diagnosis is therefore essential. Transesophageal echocardiography can show the pulmonary venous anastomosis and, combined with color flow and Doppler imaging, offer a quick and reliable method of diagnosis. Prevention of this complication entails harvesting an adequate margin of left atrial tissue around the pulmonary vein orifices, meticulous surgical anastomosis, and the use of anticoagulation in the presence of a thrombogenic tendency in the recipient. PMID- 8443197 TI - Exercise performance after lung transplantation. AB - Heart-lung, double lung, and single lung transplantation have been shown to be effective in the treatment of patients with advanced cardiopulmonary disorders. An overlap in indications occurs for the different procedures, and in many situations the factors that are important in selecting the best operation for a given patient have not been clearly elucidated. To determine whether the anticipated exercise capacity should be an important consideration in the selection of the optimal procedure for a given patient, we compared exercise performance in patients who had undergone the different lung transplantation procedures in the preceding year and were otherwise well. Eleven heart-lung, six double lung, and 16 single lung recipients and 28 control subjects underwent maximal symptom-limited incremental exercise tests using a cycle ergometer. At peak exercise, transplant recipients reached maximum oxygen uptakes in the range of 40% to 60% of predicted values; no significant differences existed between the means of the different transplant groups. Ventilatory factors did not appear to limit exercise in any group. The exercise responses in the transplant subjects were characterized by reduced aerobic capacity and diminished oxygen pulse, factors indicating abnormal cardiovascular performance. Our data indicate that moderate levels of exercise can be anticipated early after heart-lung, double lung, and single lung transplantation. In the absence of substantial differences in exercise capacity, other considerations would appear to be more important in guiding the selection of the optimal lung replacement procedure for an individual patient. PMID- 8443198 TI - Heart xenografting: a route not yet to trod. PMID- 8443199 TI - Denervation of the immature porcine lung impairs normal airway development. AB - Reimplantation or allotransplantation of the immature porcine left lower lobe results in long-term functional dynamic airway obstruction that is associated with abnormally small distal airways. We have attributed this small airway size to bronchoconstriction resulting from chronic denervation rather than to impaired airway growth. To further investigate these findings, we transplanted mature left lower lobes from adult pigs into young piglets after left pneumonectomy. After approximately 12 weeks of somatic growth, the lobes were harvested and fixed through the airways with formalin. Cross-sectional areas of terminal, noncartilaginous airways from the lung periphery were traced on a video monitor. Five groups were examined: control innervated mature left lower lobes, innervated left lower lobes subjected to compensatory growth after left upper lobectomy at approximately 9 weeks of age, mature left lower lobe transplants, reimplanted immature left lower lobe autografts, and transplanted immature left lower lobe allografts. Unlike the immature porcine lobe, transplantation of the mature porcine lobe does not result in abnormally small airways. The small airways seen after transplantation or reimplantation of the immature porcine lobe are likely, therefore, to be due to impaired airway development and not to bronchoconstriction caused by denervation. PMID- 8443200 TI - The medical and surgical determinants of heart transplantation outcomes: the results of a consensus survey in the United States. AB - Heart transplantation may well be the most successful transplantation procedure performed today. One-year patient survival rates now exceed 80%. Many factors are thought to account for differences in outcomes among transplantation centers. No attempt has been made to assess consensus among transplantation program directors regarding the major determinants of patient outcome. In the National Cooperative Transplantation Study we evaluated consensus through a detailed survey of all heart transplantation programs active in the United States in 1988. Of the eligible programs, 104 (91%) returned completed surveys. Data on the medical and surgical determinants of outcomes have been analyzed descriptively. Considerable consensus occurred among program directors about the importance of several factors. For example, over 90% of the respondents felt that heart biopsy should be used as the standard rejection monitoring technique and that left and right heart catheterization should be performed annually with coronary arteriography. Over 60% believed that the availability of a left ventricular assist device for temporary use would also enhance patient outcome. Several approaches were considered to have little beneficial effect on outcome. These included cytoimmunologic monitoring and electrocardiography as standard rejection monitoring techniques. Nearly one half of the respondents opposed steroid discontinuation after transplantation. On several other approaches there was a lack of consensus including the use of heterotopic heart transplantation and conversion from cyclosporine because of renal dysfunction. Consensus conferences are now regarded as a means by which technologic innovations can be evaluated and medical practice guidelines can be set. This analysis suggests that consensus is a useful approach toward assessing medical and surgical practices in heart transplantation. PMID- 8443201 TI - Returning to work after heart transplantation. AB - The purpose of this study was to determine what factors influence a patient's return to work after heart transplantation. Two hundred fifty patients who had undergone heart transplantation were surveyed at seven regional centers in the United States (five of which were Medicare-certified). Of these patients, 45% were employed, 36% were unemployed, 13% were medically disabled, and 6% had retired. A stepwise discriminant analysis resulted in the selection of six variables that helped differentiate those patients who did and those who did not return to work after the transplantation. The factors associated with a patient's return to work included (1) self report of being physically able to work, (2) no loss of health insurance, (3) longer length of time after transplantation, (4) education level of more than 12 years, (5) no loss of disability income, and (6) shorter length of disability before heart transplantation. This information could accurately profile 91% of the patients who were employed, 69% of the patients who were unemployed, and 80% for the entire group. The implication of this study is that social rehabilitation is not synonymous with the medical results of heart transplantation. More attention to social rehabilitation is required if heart transplant recipients are to enjoy a better quality of life and become fully productive members of the community. PMID- 8443202 TI - Prolonged preservation of human pediatric hearts for transplantation: correlation of ischemic time and subsequent function. AB - Ninety-one infants and children, aged 0 days to 12 years, who received 93 hearts from donors aged 2 days to 24 years between November 1985 and September 1990 were retrospectively studied. Forty-three children were less than 1 month of age; 31 children were between 1 month and 6 months of age, and 19 children were between 6 months and 12 years of age. The donor heart ischemic time ranged from 51 minutes to 8 hours 17 minutes (mean, 4 hours 2 minutes). Fifty-one hearts had an ischemic time of less than 4 hours (group 1), and 42 hearts, more than 4 hours (group 2). No significant difference was noted in the age of donor or recipient or in donor/recipient weight ratio. No correlation was found between ischemic time and number of primary graft failures between groups. Inotropic support was required for 3.9 +/- 3.3 and 5.2 +/- 3.7 days for group 1 versus group 2 (not significant). Ventilator status was the same between the groups. A significant decrease of posterior wall movement in diastole (p < 0.01) occurred among patients of group 2 at 1 week after transplantation, but no difference was found between groups at 2 weeks, 1 month, and 3 months after operation. Posterior wall movement of group 2 heart grafts recovered completely by week 2. No difference was noted in the fractional shortening between the groups; but in both groups, fractional shortening significantly increased from week 1 to week 2. We conclude that ischemic times up to nearly 8 1/2 hours are well tolerated by donor hearts used in pediatric transplantation. PMID- 8443203 TI - Relaxation and imagery techniques without sedation during right ventricular endomyocardial biopsy in pediatric heart transplant patients. AB - Routine endomyocardial biopsies after heart transplantation can be performed in pediatric patients with the right internal jugular venous approach. To minimize hospital time, limit disruption of daily activities, and eliminate the need for sedation, biopsies in patients older than 7 years of age were done with relaxation and imagery techniques. No complications occurred with this method, and all patients tolerated the procedure well. PMID- 8443204 TI - Complications of endomyocardial biopsy in heart transplant patients. AB - Despite the increasing use of alternative techniques, endomyocardial biopsy remains the primary method for diagnosing cardiac allograft rejection. Improved patient longevity and an increasing number of transplantation centers are resulting in an increase in the number of biopsies performed. Although endomyocardial biopsy is usually considered a safe procedure, no large studies of the risks of endomyocardial biopsy specifically in the transplant population have been undertaken. To determine the risk of endomyocardial biopsy in these patients, we reviewed 2454 endomyocardial biopsies performed from January 1983 to December 1990 in 133 cardiac allograft patients at our institution. At the time of each endomyocardial biopsy, a worksheet was completed detailing the patient's interval history, the site of vascular introduction, the number of attempts, the number of specimens, and any complications encountered. A total of 74 (3.0%) complications occurred. Fifty-six (2.3%) complications were associated with catheter insertion, including carotid puncture (1.8%), vasovagal reaction (0.1%), and prolonged bleeding (0.4%). Complications during biopsy included arrhythmias (0.25%) and conduction abnormalities (0.2%). In addition, we observed five episodes (three patients) of allergic reaction to a reusable bioptome and one case of pacemaker dislodgement. All complications were without significant long term sequelae. In contrast to the cardiomyopathy population, no ventricular perforations or deaths occurred. Thus although endomyocardial biopsy has some risk, it continues to be a safe and effective way of monitoring rejection. PMID- 8443205 TI - Effects of triiodothyronine and vasopressin on cardiac function and myocardial blood flow after brain death. AB - Previous studies have documented decreases in serum-free triiodothyronine (T3) after brain death and improved hemodynamics with its replacement, suggesting its controversial, but promising, clinical utility for managing potential organ donors. Vasopressin is also commonly used clinically as a pressor agent after brain death. A load-independent analysis of cardiac function and an assessment of myocardial blood flow (MBF) with these agents have not been reported, however. Eighteen pigs were instrumented with left ventricular epicardial dimension transducers and a left ventricular micromanometer. MBF was assessed by standard microsphere techniques. Baseline left ventricular pressure-dimension data were collected, and brain death was induced by ligating the innominate and left subclavian arteries. Left ventricular function data were collected every 30 minutes after brain death to 6 hours or until the animal died. Microsphere injections were performed before brain death and hourly thereafter to 4 hours. At 90 minutes after brain death, animals were assigned to a vasopressin (2 units/hr, intravenously, n = 6), T3 (0.05 microgram/kg/hr, intravenously, n = 6), or control (n = 6) treatment group. Preload recruitable stroke work (PRSW), a load independent index of left ventricular function, was derived from the pressure dimension data. MBF was calculated by conventional methods. At 4 hours after brain death, PRSW and MBF decreased significantly in the control, vasopressin, and T3 groups relative to the baseline, pre-brain dead state (PRSW: -36% +/- 12%, -48 +/- 7%, -52% +/- 5%; MBF: -27% +/- 15%, -38% +/- 5%, -78% +/- 2%, respectively). Neither vasopressin nor T3, however, showed any advantage over the control group in terms of preserving left ventricular function or prolonging survival. Furthermore, these data show a marked decrease in MBF in the T3 group (p < 0.01 versus control and vasopressin groups) without a significant change in cardiac function. Analysis of endocardial to epicardial flow ratios disclosed no significant differences between groups at any time. In summary, animals treated with T3 had a greater decline in MBF than the control group at 4 hours, without any benefit to cardiac function. Further studies examining the mechanism responsible for the deterioration of MBF and cardiac dysfunction will be necessary to optimally manage the brain dead patient before organ harvest, especially regarding the precise role of T3. PMID- 8443206 TI - The effects of Ca++ on the preservation of myocardial energy and function with University of Wisconsin solution. A 31P nuclear magnetic resonance study of isolated blood perfused Langendorff pig hearts. AB - We have studied the effects of adding 0.5 mmol/L CaCl2 to University of Wisconsin solution (0.08 mmol/L free Ca++) on hypothermic heart preservation. Isolated pig hearts were subjected to 8 hours of preservation at 12 degrees C; eight hearts were arrested with Ca++ free University of Wisconsin solution, and seven hearts were arrested with Ca(++)-containing University of Wisconsin solution. The recovery of contractile function was evaluated by measuring isovolumic ventricular pressure development. 31P nuclear magnetic resonance spectroscopy was used to monitor the changes in high-energy phosphates. Compared to the hearts arrested with the Ca(++)-free University of Wisconsin solution, the heart arrested with the Ca(++)-containing University of Wisconsin solution showed significantly improved (p < 0.001) contractile functional recovery. No "stone heart" or loss of high-energy phosphates was observed on reperfusion. The hearts showed an increase in diastolic pressure during infusion of the Ca(++)-containing University of Wisconsin solution, however, to show the relationship between the addition of calcium and the increase in diastolic pressure, a second protocol was performed. A 30-minute period of ischemia was induced in thirteen hearts that were arrested at 12 degrees C with either Ca(++)-containing University of Wisconsin solution (n = 8) or Ca(++)-free University of Wisconsin solution (n = 5). Diastolic pressure was monitored during ischemia while ventricular volume was maintained constant with a balloon. The hearts arrested with the Ca(++) containing University of Wisconsin solution showed a mean rise of 5 mm Hg in diastolic pressure and a rapid decline of phosphocreatine (p < 0.001). Our results suggest that, although 0.08 mmol/L free Ca++ improves functional recovery after 8 hours of heart preservation with University of Wisconsin solution at 12 degrees C, it can increase diastolic pressure during ischemia and accelerate breakdown of the high-energy phosphate stores in the myocardium, suggesting that use of University of Wisconsin solution containing 0.5 mmol/L CaCl2 may result in a significant increase in the intracellular calcium level. PMID- 8443207 TI - Coronary artery disease after heart transplantation: timing of coronary arteriography. AB - The increasing numbers of long-term survivors after heart transplantation make yearly coronary arteriography, used by most centers to study the development of transplant coronary artery disease, less practical. Therefore the prevalence and clinical relevance of coronary artery disease in 119 one-year survivors of heart transplantation were studied. Visual analysis revealed two main patterns of vascular changes: abnormalities of the epicardial vessels and their major branches and abnormalities of the tertiary branches. The prevalence of all abnormalities in the coronary vascular tree increased from 34% after 1 year to 79% after 5 years. The prevalence of anatomically significant lesions (more than 50% stenosis in the epicardial branches or abrupt ending/proximal occlusion of tertiary branches) was only 11% after 5 years. During follow-up of 25 to 87 (median, 43) months, no significant coronary artery disease developed in the 101 patients who showed normal epicardial vessels or abnormal tertiary branches only at their first year angiography, and none of the patients died of ischemic heart disease. Of the 18 patients with abnormal epicardial vessels, three patients died of ischemic heart disease; one of these patients was treated with atherectomy and is alive at the moment of this report, and two patients showed progression of discrete lesions without evidence of ischemia until now. Based on these findings, a schedule for timing of arteriography was developed depending on the first-year coronary findings. PMID- 8443208 TI - The role of arginine in the conserved polar loop of the c-subunit of the Escherichia coli H(+)-ATPase. AB - The Arg-41 of the c-subunit of the F0F1-ATPase of Escherichia coli has been changed by site-directed mutagenesis to Glu, Leu or Lys. None of the mutants can carry out oxidative phosphorylation. No detectable F1-ATPase activity is found on the membranes and only small amounts in the cytoplasm. Two-dimensional gel electrophoresis shows that in all three mutant strains the assembly of the F0F1 ATPase has been affected. When plasmids carrying the mutant genes, together with other normal unc genes, were inserted into strains each carrying a mutation in one of the unc genes other than uncE their capacity for oxidative phosphorylation was reduced or eliminated, the effect being most pronounced with the uncG and uncC mutants and least pronounced with the plasmid giving the Arg-->Lys substitution. The c-subunit is a multimer in the ATP synthase complex and it appears that a mixture of normal and mutant gene products allows assembly of a functional complex. PMID- 8443209 TI - Characterization of NAD(P)H-dependent ubiquinone reductase activities in rat liver microsomes. AB - Exogenous ubiquinone-10 was efficiently reduced by rat liver microsomes in the presence of NADH and NADPH under anaerobic conditions. Ubiquinone-10 reduced under anaerobic conditions was rapidly re-oxidized by the re-aeration. The reduction and re-oxidation were not observed when the reactions were carried out with the boiled microsomes or without microsomes, suggesting that the reactions were enzymatically catalyzed by the electron transport system(s) from NAD(P)H to O2 through the ubiquinone. The Km and Vmax of the reductase activity for NADH were 0.4 mM and 1.7 nmol/min per mg of protein, and those for NADPH were 19 microM and 2.1 nmol/min per mg of protein, respectively. The NADH-dependent oxidoreduction system was different from the NADPH-dependent system because of the following observations; (1) rotenone inhibited only the NADH-dependent ubiquinone-10 reductase, (2) dicoumarol inhibited the NADPH-dependent ubiquinone 10 reduction more potently than the NADH-dependent reduction and (3) the activity oxidizing the reduced ubiquinone-10 in the presence of NADH was less than that in the presence of NADPH. Endogenous ubiquinone-9 was also reduced and re-oxidized in essentially the same manner as exogenous ubiquinone-10. Thus, ubiquinone-10 oxidoreductase in rat liver microsomes acts on endogenous ubiquinone-9. PMID- 8443210 TI - Cytochrome P-450 in liver microsomes of streptozotocin-induced diabetic rats: purification and characterization. AB - Two diabetes-inducible forms of cytochrome P-450, named P-450ST-1 and -ST-2, were purified from the liver microsomes of streptozotocin-diabetic male rats by sodium cholate solubilization, octylamino-Sepharose 4B chromatography and high performance liquid chromatography with DEAE-5PW and hydroxyapatite columns. The purified P-450 forms gave a single band each on sodium dodecyl sulfate polyacrylamide gel electrophoresis, with an apparent molecular weight of 48,500 for P-450ST-1 or 48,000 for P-450ST-2. The CO-reduced spectral maxima of P-450ST 1 and -ST-2 were at 451 nm. The two cytochromes had the low-spin state of heme in the oxidized form. Both P-450ST-1 and -ST-2 catalyzed the metabolism of aniline, benzphetamine, p-nitroanisole, testosterone and aminopyrine. However, the catalytic activity of P-450ST-2 for these substrates was apparently higher than that of ST-1. Analyses of the NH2-terminal amino-acid sequence and Western immunoblot showed that P-450ST-1 and -ST-2 differed structurally from each other. The catalytic activities, molecular weights, NH2-terminal sequences and/or immunochemical properties of P-450ST-1 and -ST-2 did not agree with those of the other cytochrome P-450 forms purified from diabetic rats previously. PMID- 8443211 TI - Characterization of two low-potential cytochromes from bean sprouts. AB - Two cytochromes have been isolated from chlorophyll-free bean sprouts, purified and characterized. The more abundant cytochrome was purified to apparent homogeneity and exhibits visible region absorbance maxima at 416, 520 and 550 nm in the reduced form and at 410 and 530 nm in the oxidized form. Although Resonance Raman spectra of this cytochrome closely resemble those of c-type cytochromes, pyridine hemochromogen analysis suggests that this cytochrome may contain a variant of heme c as its prosthetic group. The cytochrome has an apparent molecular mass of 12.5 kDa, an isoelectric point > 9.0 and a midpoint oxidation-reduction potential (Em) of -130 mV at pH 8.0. The less abundant of the two cytochromes, which was not completely purified, exhibits absorbance maxima at 438 and 560 nm in the reduced form and at 411 nm in the oxidized form and was shown to contain heme c as a prosthetic group. This cytochrome, which may also contain FAD, has an apparent molecular mass of approx. 38 kDa, an isoelectric point > 9.0 and Em = -300 mV. Preliminary results indicate that both cytochromes can form electrostatically-stabilized complexes with ferredoxin, suggesting the possibility that one or both of the cytochromes may participate in low-potential, non-photosynthetic electron transfer pathways involving ferredoxin. PMID- 8443212 TI - Kinetics of the mitochondrial NADH-ubiquinone oxidoreductase interaction with hexammineruthenium(III). AB - The steady-state kinetics of the NADH dehydrogenase activities of the mitochondrial NADH-ubiquinone oxidoreductase in the presence of one-electron acceptors, ferricyanide and hexammineruthenium(III), were studied. Similar to ferricyanide, hexammineruthenium was found to be an efficient electron acceptor for the enzyme in inside-out submitochondrial particles and isolated Complex I, but not in intact mitochondria. Qualitatively the same results were obtained using submitochondrial particles or isolated Complex I. Both hexammineruthenium(III) and ferricyanide reduction was rotenone-insensitive and showed no stimulation by the uncouplers in tightly coupled submitochondrial particles. In contrast to the NADH-ferricyanide oxidoreductase reaction which exhibits a double substrate inhibition behaviour, no inhibition of the reaction by either NADH or the electron acceptor was revealed in the NADH hexammineruthenium(III) reductase reaction. The double-reciprocal plots 1/v vs. 1/[NADH] at various hexammineruthenium(III) concentrations gave a series of straight lines intercepting in the third quadrant, thus supporting the mechanism of the overall reaction in which the reduced enzyme-NAD+ complex is oxidized by the electron acceptor before NAD+ dissociation. The apparent KsNADH values equal to 1 x 10(-5) and 4 x 10(-5) M for submitochondrial particles and Complex I, respectively (27 degrees C, pH 8.0), were determined from the secondary KmNADH vs. V (at different acceptor concentrations) plot. The Ki values for the competitive inhibition of NADH oxidation by NAD+ were 1 x 10(-3) M and 2 x 10(-3) M for the respective enzyme preparations. The results obtained suggest that hexammineruthenium(III) interacts with the NADH-ubiquinone oxidoreductase at a single reaction site different from that for fericyanide. PMID- 8443213 TI - Characterization of betaine efflux from rat liver mitochondria. AB - In order to investigate the control of endogenous betaine supply to the cytoplasmic enzyme betaine-homocysteine methyltransferase, it was necessary to understand how betaine synthesized within the mitochondrial matrix is transported across the mitochondrial inner membrane. Mitochondria were loaded with radiolabelled betaine and efflux was measured in a medium at physiological ionic strength. Efflux of radiolabelled betaine occurred continuously with time. The efflux rate was unaffected by the presence or absence of a source of energy except at high membrane potentials, where betaine efflux rate increased 2-3-fold. Titration of the membrane potential demonstrated a non-ohmic relationship between betaine efflux rate and membrane potential. The rate of betaine efflux was proportional to the matrix betaine concentration up to 9 mM. Efflux was unaffected by addition of analogues of betaine and known mitochondrial transport inhibitors. N-Ethylmaleimide did inhibit efflux by 50%, but evidence suggested that the effect was non-specific. The lack of saturability or other evidence for a transport system suggests that betaine escapes from mitochondria by simple diffusion. The relative diffusion rates of glycine, sarcosine, dimethylglycine and betaine suggest that increasing the degree of N-methylation lowers diffusion rate. PMID- 8443214 TI - Purification and properties of cytochrome bo-type ubiquinol oxidase from a marine bacterium Vibrio alginolyticus. AB - Ubiquinol oxidase was extracted from membranes of a marine bacterium Vibrio alginolyticus with a nonionic detergent Liponox DCH and was purified about 130 fold by DEAE-Sephacel, DEAE-5PW and Sephacryl S-300. The purified ubiquinol oxidase was composed of three subunits with apparent M(r) of 79, 36 and 13 kDa on SDS-polyacrylamide gel electrophoresis. The oxidase contained cytochrome b, cytochrome o and copper atoms. The presence of heme O was confirmed by reverse phase HPLC analysis. Ubiquinol-1, duroquinol and tetramethylphenylene diamine, but not horse heart reduced cytochrome c, were oxidized by this enzyme. The oxidase required no salts for activity and was stimulated by several detergents and by diphosphatidyl glycerol. The activity was strongly inhibited by KCN, 2-n heptyl-4-hydroxyquinoline N-oxide and ZnSO4. These properties were essentially similar to those of cytochrome bo-type ubiquinol oxidase from Escherichia coli, suggesting that the bo-type ubiquinol oxidase is functioning as a proton pump in the marine V. alginolyticus. PMID- 8443215 TI - Biophysical and biochemical alterations of renal cortical membranes in diabetic rat. AB - The objective of this study was to determine whether streptozotocin-induced diabetes mellitus in the rat causes alterations in the lipid composition and fluidity of renal brush border membranes (BBM) and basolateral membranes (BLM). Compared to membranes of non-diabetic rats, BBM and BLM of diabetic rats contained 31% and 26%, respectively, less arachidonic acid and 36% and 46%, respectively, more linoleic acid esterfied in phospholipids. These changes were accompanied by a decrease in the average number of double bonds per mole of fatty acid, a measure of fatty acid unsaturation. In diabetic rats BLM had a higher total phospholipid/protein ratio (567 +/- 20 vs. 482 +/- 15 nmol/mg protein, P < 0.01), less cholesterol (369 +/- 30 vs. 512 +/- 34 nmol/mg protein, P < 0.01), more phosphatidylcholine (+72%) and less sphingomyelin (-22%) than did BBM. These differences were identical to those observed between BLM and BBM of non-diabetic rats. In control rats BLM was more fluid than BBM as assessed by the steady state fluorescence anisotrophy of diphenylhexatriene and by glycerol permeability. In diabetic rats the fluidity of BLM was not different from that of BBM as assessed by the steady state fluorescence anisotrophy of diphenylhexatriene whereas BLM was slightly more fluid than BBM as assessed by glycerol permeability. By both measures BLM and BBM from diabetic rats were significantly less fluid than BLM and BBM from control rats. Removal of proteins and cholesterol in sequence was accompanied by an increase in membrane fluidity in both groups. However, in no instance did the removal of proteins or cholesterol abolish the difference between the fluidity of diabetic membranes and that of control membranes. From these data we conclude that the reduction in fluidity of renal BLM and BBM in the diabetic rat is due to the change in the composition of fatty acids esterified in membrane phospholipids. PMID- 8443216 TI - Characterization of proton transport in bone-derived membrane vesicles. AB - ATP-dependent proton transport in membrane vesicles prepared from the medullary bone of egg-laying hens, a source rich in osteoclasts, was characterized. Proton transport was abolished by bafilomycin A1 (10 nM) and N-ethylmalemide (50 microM), but not by oligomycin (15 micrograms/ml), vanadate (100 microM) or SCH 28080 (100 microM), thereby differentiating this H(+)-ATPase from the F1F0- and phosphorylated-type of ATPases. Preincubation of the membrane vesicles at 0 degrees C for 1 h in the presence of KCl (0.3 M) and Mg-ATP (5 mM) resulted in almost complete loss of H(+)-transport activity (cold-inactivation). Preventing the formation of a membrane potential by voltage clamp (Kin+ = Kout+ + valinomycin) increased both the rate of H(+)-transport and the equilibrium delta pH, suggesting an electronic proton transport mechanism. Thus, the H(+)-ATPase in this bone-derived membrane vesicle preparation shows the characteristics of a vacuolar H(+)-ATPase in its inhibitor- and cold-sensitivity and its electrogenic mechanism. The anion sensitivity of the H(+)-ATPase was investigated by varying the intra- and/or extra-vesicular salt composition. The H(+)-ATPase had no absolute requirement for any specific anion, but membrane permeable anions were found to stimulate proton transport activity, presumably by acting as charge compensators for the electrogenic hydrogen ion transport. However, some anions, such as sulfate, acetate and nitrate were directly inhibitory to the ATPase. The results are in agreement with the recently proposed mechanism of osteoclast acidification: a vacuolar H(+)-ATPase working in parallel with a Cl(-)-channel resulting in electroneutral HCl secretion. PMID- 8443217 TI - Mechanism of uptake of the fluorescent dye 2-(4-dimethylaminostyryl)-1 ethylpyridinium cation (DMP+) by phospholipid vesicles. AB - The fluorescent dye 2-(4-dimethylaminostyryl)-1-ethylpyridinium cation (DMP+) is taken up by liposomes of egg phosphatidylcholine in response to the imposition of a transmembrane potential. Entry of DMP+ into the bilayer driven by the transmembrane potential is accompanied by a change in the fluorescence emission maximum of the dye. This change reflects the movement of the dye molecules from the headgroup region of the bilayer into the region of the fatty acyl chains. It is released into the external aqueous phase on discharge of the transmembrane potential. Partition of the dye into the phospholipid bilayer is favoured by the presence of negatively charged lipids, such as dioleoylphosphatidic acid and dicetyl phosphate, in the bilayer. Stearylamine opposes entry of the dye into the bilayer. Tetraphenylboron (TPB-) increases the partitioning of DMP+ into the phospholipid bilayer even in the absence of a transmembrane potential. The fluorescence emission maximum of DMP+ under these conditions is similar to that observed in the absence of TPB- following imposition of the transmembrane potential. It is suggested that TPB- facilitates the entry of DMP+ into the fatty acyl chain regions of the phospholipid bilayer. PMID- 8443218 TI - The transport mechanisms of organic cations and their zwitterionic derivatives across rat intestinal brush-border membrane. 1. Binding characteristics to the bio- and lipid-membranes. AB - The uptake mechanisms of organic cations such as tryptamine, tyramine, 5 benzyloxytryptamine (BOTA) and their zwitterionic derivatives (tyrosine, tryptophan, 5-benzyloxytryptophan (BOTP)) by rat intestinal brush-border membrane vesicles and liposome containing phosphatidylserine were studied and compared. As compared to their zwitterionic derivatives, uptake rates by rat intestinal brush border membrane of these three cations were far superior. The binding of cationic compounds to the brush-border membrane was also higher than those of their zwitterionic derivatives. Furthermore, the binding behaviour of BOTA and tryptamine to phospholipid liposome clearly amplified with increasing amounts of phosphatidylserine. In contrast, the contents of phosphatidylserine, a negatively charged phospholipid, exhibited no effects on the binding of zwitterionic derivatives (tryptophan and BOTP). The double-reciprocal plot of tryptamine binding with BOTA to liposome showed competitive inhibition. These results suggest that the binding of organic cations to the membrane lipid has a relatively high specificity despite the absence of membrane protein such as a transport-carrier in the liposome, and that the binding of cationic compounds play an important role in the uptake to the cell membrane systems. PMID- 8443219 TI - Perturbation of the chain melting transition of DPPC by galactose, agarose and Laurdan as determined by differential scanning calorimetry. AB - Differential scanning calorimetry was used to determine the effects of agarose hydrogel, galactose and the fluorophore Laurdan on the thermal behavior of multilamellar liposomes of DPPC. Although the effect of agarose on the phase transition was found to be negligible at low concentrations (< or = 2.5%), higher concentrations result in an endotherm that broadens and splits into two calorimetric events, one of which is at a higher temperature than that of hydrated DPPC. Equal weight fractions of galactose produce similar effects, although both fractions have raised melting temperatures. The higher melting components may be produced by osmotically-driven dehydration of the inner liposomal monolayers, a physical interaction between the carbohydrates and lipid headgroups, or a combination of both. Laurdan has little effect on the phase transition of DPPC vesicles at the concentration used in the sensor (0.67 mol%); concentrations up to 5.4 mol% only slightly lowered the melting temperature. PMID- 8443220 TI - Use of merocyanine (MC540) in quantifying lipid domains and packing in phospholipid vesicles and tumor cells. AB - The fluorescent probe merocyanine (MC540) reports qualitatively on several membrane events. Here we demonstrate that MC540 fluorescence can quantify the degree of coexisting liquid-crystalline and gel states in mixed monotectic phosphatidylcholine (PC) bilayers. The probe exhibits disparate fluorescence wavelength maximas and and intensities when incorporated into liquid-crystalline and gel state membranes. The fluorescence measurements partitioning of the EPR spin probe TEMPO between the aqueous environment and the membrane fluid phase. While both techniques can accurately assess the phase transition of synthetic PCs, only MC540 can distinguish between liquid-crystalline phases of different composition. MC540 fluorescence for single-component PC bilayers correlates quantitatively with estimates of the area/molecule determined from surface area/pressure isotherms of lipid monolayers, whereas partitioning of TEMPO fails to assess the relative degree of lipid packing in various fluid state membranes. Additionally, MC540 fluorescence characterizes the interaction of cholesterol with membranes made from condensable (18:0, 18:1-PC) and non-condensable (18:0, 22:6-PC) lipids. Finally MC540 distinguishes tumor cell membranes differing only in the amount of docosahexaenoic acid (DHA). Thus we conclude that MC540 can be used quantitatively to study phospholipid packing and membrane phases with lipid vesicles and to sense subtle differences in the arrangement of phospholipids in biological membranes. PMID- 8443221 TI - Uric acid transport in rat renal basolateral membrane vesicles. AB - Pathways for urate transport across the basolateral membrane of rat proximal tubule cells were investigated using membrane vesicles isolated from rat renal cortex. The presence of an anion exchange mechanism(s) operative in the mode of alpha-keto-glutarate/urate; Cl-/urate and OH-(HCO3-)/urate as well as a mediated conductive mechanism was assessed from tracer flux measurements. In the presence of an inwardly directed Na+ gradient an alpha-ketoglutarate dependent concentrative accumulation of PAH but not urate was observed suggesting an absence of the mediated exchange of alpha-ketoglutarate for urate. The imposition of an outwardly directed Cl- gradient stimulated urate uptake in the absence but not the presence of conditions designed to minimize membrane potential development suggesting an indirect electrostatic coupling of urate uptake to a Cl gradient-induced diffusion potential. Conditions favoring the development of an inside-positive K+ diffusion potential was observed to induce an inhibitor sensitive, concentrative accumulation of urate in the absence of Cl-. The stimulation of urate uptake measured in the presence of an inside-alkaline pH gradient was not of sufficient magnitude to suggest the apparent conductive urate uptake was secondary to a membrane voltage induced, inside alkaline pH gradient and the operation of an OH-(HCO3-)/urate exchanger. The evidence obtained from the present investigation suggests rat basolateral membrane urate transport occurs by a mediated, conductive mechanism and is not coupled to Cl-, alpha ketoglutarate or HCO3-.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8443222 TI - Electron diffraction study on two-dimensional domain structure of L-DPPC monolayer. AB - A spatial variation in the two-dimensional crystal lattice orientation of L-DPPC monolayer on a hydrophobic substrate was observed by use of an electron microscope with diffraction and dark-field techniques. It is shown that the monolayer has a mosaic structure with domains, each of which consists of a region with a homogeneously oriented lattice of L-DPPC molecules. The domain structure of L-DPPC monolayer on a hydrophilic surface is also discussed. PMID- 8443223 TI - Thermodynamic characterization of the association of small basic peptides with membranes containing acidic lipids. AB - We measured the binding of the peptide acetyl-Trp-Lys7-amide to membranes formed from mixtures of the zwitterionic lipid 1-palmitoyl-2-oleoyl-sn-glycero-3 phosphocholine (PC) and the acidic lipid 1-palmitoyl-2-oleoyl-sn-glycero-3 phosphoglycerol (PG). Direct filtration and equilibrium dialysis measurements demonstrate that binding increases sigmoidally with the mole fraction of PG as predicted from a simple Gouy-Chapman/mass action theoretical model. We used these measurements to calibrate two binding assays, one based on the increase in Trp fluorescence that occurs when the peptide binds to the membrane, the other on the quenching of Trp fluorescence that occurs when the peptide binds to membranes containing fluorescent lipids. Both fluorescence assays demonstrate that binding does not depend strongly on temperature, which suggests the enthalpy change, delta H, is small. Calorimetric measurements demonstrate this directly for the analogous basic peptide Lys5: delta H congruent to +1 kcal/mol for the binding of Lys5 to sonicated phospholipid vesicles and delta H congruent to 0 kcal/mol for its binding to large unilamellar vesicles. Thus, the decrease in the free energy that occurs when these peptides bind to the membrane is due to a positive change in the entropy of the system. Fluorescence measurements demonstrate the binding of the Trp-containing peptide to 4:1 PC/PG membranes is independent of pressure up to 2 kbar, which suggests that binding occurs without a significant change in volume. PMID- 8443224 TI - Sodium transport by an ionizable and a neutral mobile carrier: effects of membrane structure on the apparent activation energy. AB - Temperature-jump relaxation experiments on Na+ transport by (221)C10-cryptand (ionizable mobile carrier) and nonactin (neutral mobile carrier) were carried out in order to study the effects of cholesterol and the degree of acyl chain unsaturation, and their temperature-dependence on ion transport through thin lipid membranes. The experiments were performed on large, negatively charged unilamellar vesicles (LUV) prepared from mixtures of phosphatidylcholine (egg phosphatidylcholine, dioleoylphosphatidylcholine and dilinoleolylphosphatidylcholine), phosphatidic acid and cholesterol (mole fractions 0-0.43), at various temperatures and carrier concentrations. The apparent rate constants of Na+ translocation by (221)C10 and nonactin increased with the carrier concentration, the degree of acyl chain unsaturation and the temperature. The incorporation of cholesterol into the membranes significantly reduced the carrier concentration-, acyl chain unsaturation- and temperature dependence of this parameter. The apparent energy required to activate the transport decreased significantly with increasing (221)C10 concentrations and remained constant with increasing those of nonactin at any given cholesterol molar fraction and degree of acyl chain unsaturation. It increased significantly with increasing the cholesterol molar fraction at any given carrier concentration to an extent depending on the degree of acyl chain unsaturation. Our interpretation of the action of cholesterol on these transport systems is based on the assumption that the adsorption plane of Na(+)-(221)C10 and Na(+)-nonactin complexes is likely to be located towards the aqueous and the hydrocarbon side of the dipole layer, respectively. The results are discussed in terms of the structural, physico-chemical and electrical characteristics of carriers and complexes, and of the interactions occurring between an ionizable or a neutral mobile carrier and the membrane. PMID- 8443225 TI - The cation receptor subsite of the choline transporter in preimplantation mouse conceptuses resembles a cation receptor subsite of several amino acid transporters. AB - Mediated choline transport in preimplantation mouse conceptuses was inhibited competitively by Na+ and other cationic osmolites. Uptake of choline by conceptuses was also inhibited relatively strongly by ethanolamine, hemicholinium 3, harmaline, harmalol and harmine. The Ki values for inhibition of choline transport by most of the latter inhibitors were of the same order of magnitude as the Km value for choline transport (approximately 100 microM). To our knowledge, we are the first to show that mediated 'Na(+)-independent' choline transport is, nevertheless, inhibited strongly by the Na(+)-site inhibitor, harmaline. Inhibitions by harmaline, Na+ and other cations have been used to draw a parallel between the substrate receptor sites of amino acid transport systems y+ and bo.+. We suggest that the latter parallel should be extended to include the Na(+) independent mammalian choline transporter. In addition, the choline transport activity in conceptuses increased by more than 100-fold between the 2-cell and blastocyst stages of development. Mouse blastocysts probably utilize choline for the synthesis of membrane phospholipids during cellular differentiation and when they begin to grow about ten hours prior to implantation. Since we show here that mouse conceptuses develop the capacity to transport choline prior to the onset of growth, some of the choline utilized for growth could come from an exogenous source. PMID- 8443226 TI - FTIR spectroscopic analysis of the amide and acid bands of ganglioside GM1, in pure form and in mixtures with DMPC. AB - The amide I bands of sphingolipids show complicated patterns due to intra- and intermolecular interactions via hydrogen bonds. In order to assign the amide I absorption bands of the ganglioside GM1 to the different amide groups in the headgroup and back bone, the compounds N-acetylgalactosamine, N-acetylneuraminic acid, glucocerebroside and ceramide III were examined as reference systems. The frequencies of the COOH and COO- bands of the sialic acid residue of GM1 were determined by pH-titration and were found to absorb at 1729 cm-1 and 1605 cm-1, respectively. In D2O the three amide groups of GM1 give one broad absorption band at 1627 cm-1, whereas in the glucocerebroside intra- and intermolecular interactions of the amide group give rise to three distinct amide I bands. For a solid sample of GM1 in KBr also one broad band was observed in the amide I region. We also studied the influence of the ganglioside GM1 on model membranes of DMPC as host lipid. The change of the CH2 stretching vibrational absorption bands as a function of temperature reveal that addition of GM1 to DMPC leads to increased phase transition temperatures Tm with increasing ganglioside content. No Ca2+ binding to the COO- group of GM1 was observed. PMID- 8443227 TI - Cibacron blue-induced enhancement of agonist binding to cholecystokinin (CCK) receptors in solubilized pancreatic membranes. AB - The pancreatic receptor for cholecystokinin (CCK) typifies many G protein-coupled receptors in that its ability to bind agonist can be reduced by GTP or the solubilization of membranes. We found, however, that a dye, cibacron blue, caused up to a 6-fold increase in binding of the CCK receptor agonist, 125I-CCK-8, to rat pancreatic membranes solubilized with digitonin. Binding optimally enhanced in this manner was comparable to binding of 125I-CCK-8 to native membranes with respect to time-course, maximal amount bound, reversibility, and sensitivity to inhibition by various CCK receptor ligands. Increases in affinity of the CCK receptor for CCK-8 accounted fully for the enhancement of binding of 125I-CCK-8. Cibacron blue did not enhance binding of 125I-CCK-8 to native membranes, and also failed to enhance binding of the CCK receptor antagonist, [3H]L-364,718, to solubilized or native membranes. The ability of cibacron blue to enhance binding of agonist but not that of antagonist suggests that this dye may mimic or perhaps stimulate the effects of G protein on CCK receptors. Such a phenomenon may provide new insights into the mechanisms by which receptors distinguish agonists from antagonists. PMID- 8443228 TI - Ceramide excluded from cell-free vesicular lipid transfer from endoplasmic reticulum to Golgi apparatus. Evidence for lipid sorting. AB - The distribution and cell-free transfer of ceramide and other lipids were compared using highly purified fractions of endoplasmic reticulum, transitional endoplasmic reticulum, transition vesicles and Golgi apparatus from rat liver. Ceramides were present in both endoplasmic reticulum and Golgi apparatus where they represented between 0.3 and 1% of the total lipids. Ceramides, however, were much reduced or absent (< 0.05%) from transition vesicles. Transition vesicles were induced to form from transitional endoplasmic reticulum by incubation with ATP and a cytosol fraction. When transfer of [14C]choline-labeled phosphatidylcholine from transitional endoplasmic reticulum to Golgi apparatus was followed, transition vesicles were more efficient in transfer than the transitional endoplasmic reticulum from which they were derived. This transfer was temperature- and ATP-dependent and inhibited by N-ethylmaleimide. When transfer of [3H]ceramide was followed, there was little or no transfer via transition vesicles and that transfer which occurred was temperature-, ATP- and N ethylmaleimide independent. Transfer of ceramide in the cell-free system did occur from endoplasmic reticulum to Golgi apparatus but via a non-vesicular mechanism that was temperature-dependent but not dependent on ATP or cytosol, alone, or in combination, nor was it inhibited by N-ethylmaleimide. A component of phosphatidylcholine transfer exhibited similar characteristics. The results provide evidence for two distinct mechanisms for cell-free transfer of lipids from endoplasmic reticulum to Golgi apparatus. The first is via 50 to 70 nm transition vesicles which is temperature- and ATP-dependent, inhibited by N ethylmaleimide and from which ceramides are excluded. The second is non vesicular, temperature-dependent, and neither ATP- nor cytosol-dependent. It accounts for the bulk of the ceramide transfer. As a result during cell-free lipid transfer from endoplasmic reticulum to Golgi apparatus, lipid sorting occurs such that ceramides are largely absent from the transition vesicles and, apparently are delivered to the Golgi apparatus by another mechanism. PMID- 8443229 TI - Phospholipid methylation in brain membrane preparations: kinetic mechanism. AB - The methylation reactions which convert phosphatidylethanolamine (PE) to phosphatidylcholine (PC) have been studied kinetically using exogenously added intermediates and crude membrane preparations from brain. The addition of exogenous PE resulted in no change in the methylation rates compared to that of endogenous PE. The addition of the two intermediates, monomethylphosphatidylethanolamine (PMME) and dimethylphosphatidylethanolamine (PDME), resulted in significantly increased rates of methylation and allowed the kinetic analysis of these latter two methylation reactions. The mechanism for this enzyme appears to be similar to human RBC (Reitz et al. (1989) J. Biol. Chem. 264, 8097-8106) which was a rapid-equilibrium random Bi-Bi sequential mechanism. There were some slight differences between the brain enzyme and that from the RBC, but there is little reason to suggest a fundamentally different mechanism. It is more likely that the differences may relate to an additional dead-end complex for the enzyme from brain such that saturation with AdoMet cannot eliminate AdoHcy inhibition. The KM values for the two phospholipid substrates were 41-44 microM and 39 microM for the methylation of PMME and PDME, respectively. The KM for S-adenosylmethionine (AdoMet) was 7-9 microM with PMME and 4 microM with PDME as the other substrates. The Ki(lipid) varied from 54 microM with PMME to 225 microM with PDME, and the Ki(AdoMet) was 11 microM with PMME and 21 microM with PDME. The product from the use of AdoMet, S adenosylhomocysteine (AdoHcy), was shown to be a noncompetitive inhibitor of both lipid substrates as well as AdoMet. The methylation of PMME was somewhat higher in cerebellum and brain stem compared to cortex and striatum, but the methylation of PDME was similar in cerebellum, brain stem and cortex. PMID- 8443230 TI - Effect of cholesteryl ester on the distribution of fluorescent cholesterol analogues in triacylglycerol-rich emulsions. AB - Lipid emulsions consisting of a surface monolayer of phospholipid enclosing a core of neutral lipid (cholesteryl ester and/or triacylglycerol) are useful models of the lipid phase of lipoproteins. The physical state of the emulsion surface may determine the extent and nature of interaction of enzymes and lipid transfer proteins (e.g., lipoprotein lipase, cholesteryl ester transfer protein) with the particle. Unesterified cholesterol, which is a major determinant of the physical state of the surface phase, is able to partition between surface and core compartments. This report describes a fluorescence quenching method which determines the equilibrium distribution of a fluorescent cholesterol analogue (dehydroergosterol) between the surface and core compartments of triacylglycerol rich emulsions. Quenching by iodide is used to distinguish a pool of unesterified cholesterol readily accessible to the aqueous phase. Quenching by 5 nitroxystearate identifies a pool of unesterified cholesterol in the phospholipid monolayer and the pool of unesterified cholesterol in the core compartment is found by difference. It is shown that the substitution of cholesteryl oleate for triolein in the core of the emulsion substantially increases the partition of unesterified cholesterol into the core compartment with a consequent depletion of unesterified cholesterol in the surface monolayer. The distribution of unesterified cholesterol between surface and core compartments is largely enthalpically driven. PMID- 8443231 TI - Structural studies of lipid fibers formed by sphingosine. AB - The natural product D-erythro-sphingosine and synthetic racemic dihydrosphingosines were examined for their abilities to self-assemble into high axial-ratio microstructures. When precipitated from methanol/water solution, D erythro-sphingosine formed a viscoelastic gel composed of 50-nm diameter flexible fibers. These are 'cochleate cylinders' composed of rolls of lamellae. Compared to the biological sphingosine, the DL-erythro- and DL-threo-dihydrosphingosines are much less soluble in methanol/water mixtures. When recrystallized from methanol/water the dihydrosphingosines tend to form irregular lamellar structures or platelets. When higher proportions of methanol are used in the recrystallization solvent, needle-like structures predominate in the DL-erythro dihydrosphingosine sample, but not in the DL-threo-dihydrosphingosine samples. The needles are mostly very long and narrow crystal platelets often with fracture defects parallel to the long axes. Some curved fiber-like structures are also seen. These results suggest that in comparison to the threo diastereomer, the erythro diastereomer of dihydrosphingosine displays a large differential in intermolecular bonding strengths between divergent orientations within the lamellar sheet. Energy-minimized molecular models indicate that, compared to the threo isomers, intramolecular bonding could bend the erythro headgroup farther toward the hydrocarbon interface of a lamellar microstructure. Moreover, this work illustrates how the erythro headgroup could support a linear pattern of intermolecular hydrogen bonds while the threo could support a two-dimensional network. D-erythro-sphingosine probably displays a similar intermolecular bonding pattern, but as it is optically pure, the molecular packing results in a consistent twist to the neighboring molecules and this is expressed as the bending of the lamellar sheet into a cochleate. The fiber-forming ability of D erythro-sphingosine may have implications for the reactive and structural properties of biological sphingolipids as well as the design of novel materials based on synthetic high-axial-ratio lipid superstructures. PMID- 8443232 TI - Comparative antioxidant activity of tocotrienols and other natural lipid-soluble antioxidants in a homogeneous system, and in rat and human lipoproteins. AB - The antioxidant activity of tocotrienols toward peroxyl radicals was compared with that of other natural lipid-soluble antioxidants in three different systems by measuring the temporal disappearance of antioxidants and the formation of lipid hydroperoxides. In homogeneous solution, the initial rates of consumption of the various antioxidants, assessed by competition experiments between pairs of antioxidants for radicals, decreased in the order: ubiquinol-10 approximately ubiquinol-9 > alpha-tocopherol approximately alpha-tocotrienol > beta-carotene approximately lycopene > gamma-tocopherol approximately gamma-tocotrienol. Following in vitro incubation of human plasma with alpha-tocotrienol, this form of vitamin E was present in all classes of lipoproteins isolated from the supplemented plasma. Dietary supplementation of rats and humans with a tocotrienol-rich preparation resulted in a dose-dependent appearance of alpha- and gamma-tocotrienols in plasma and all circulating lipoproteins, respectively. Exposure of such enriched rat plasma to aqueous peroxyl radicals resulted in simultaneous consumption of the alpha- and then gamma-isomers of vitamin E. The sequence of radical-induced consumption of antioxidants in freshly isolated, in vitro and in vivo tocotrienol-enriched low density lipoprotein (LDL) was again ubiquinol-10 > alpha-tocotrienol approximately alpha-tocopherol > carotenoids > gamma-tocopherol approximately gamma-tocotrienol. Under conditions where radicals were generated at constant rates, the rate of lipid hydroperoxide formation in LDL was not constant. It proceeded in at least three stages separated by the phase of ubiquinol-10 consumption and, subsequently, that of alpha tocopherol/alpha-tocotrienol. Our results show that dietary tocotrienols become incorporated into circulating human lipoproteins where they react with peroxyl radicals as efficiently as the corresponding tocopherol isomers. PMID- 8443233 TI - The occurrence of furan fatty acids in Isochrysis sp. and Phaeodactylum tricornutum. AB - Two algae species with a fundamentally different fatty acid composition were investigated for their furan fatty acid (F-acid) content. Isochrysis sp. contains different F-acids with a pentyl side chain in alpha'-position of the furan ring. In consideration of its fatty acid composition which is predominated by compounds with a C-18 chain, this result supports the assumption that pentyl-F-acids derive from linoleic acid. In contrast, only F-acids with propyl side chain were found in Phaeodactylum tricornutum. The low content of C-18 fatty acids in this diatomae contradicts the previous hypothesis that linolenic acid is the precursor of propyl-F-acids. But the presence of (n - 4) unsaturated fatty acids with 16 carbon atoms in Phaeodactylum tricornutum suggests that propyl-F-acids are synthesized from 9,12-hexadecadienoic acid in a very similar biogenetic pathway than pentyl-F-acids. PMID- 8443234 TI - 24-, 25- and 27-hydroxylation of cholesterol by a purified preparation of 27 hydroxylase from pig liver. AB - Pig liver mitochondria were found to catalyze 27-, 25- and 24-hydroxylation of cholesterol at relative rates of about 1:0.2:0.04. An apparently homogeneous preparation of pig liver mitochondrial cytochrome P-450-27 was found to catalyze the same three hydroxylations at about the same relative rates when reconstituted with adrenodoxin and adrenodoxin reductase. The 24-hydroxycholesterol formed was shown to consist of one of the two possible stereoisomers. When using specifically deuterium-labeled substrates a significant isotope effect was observed in the case of 24-hydroxylation (KH/KD > 10), but not 25-hydroxylation (KH/KD = 1.1), or 27-hydroxylation (KH/KD = 1.1). The difference between the 24 hydroxylation and the other two hydroxylations may be due to different interactions between cholesterol and the same enzyme, with a resulting difference with respect to the rate-limiting step in the reaction. The physiological significance of the mitochondrial 24-hydroxylation is discussed. PMID- 8443235 TI - Effect of VLDL on the inhibition of arachidonic acid transformation by dexamethasone in cultured smooth muscle cells. AB - Very-low-density lipoproteins (VLDL) induce a dose-dependent reduction (up to 55%) in the number of specific binding sites and about a 2-fold increase in binding affinity for [3H]dexamethasone in human and rat smooth muscle cells (SMC). Maximal effect of VLDL was achieved within 3-5 h at a lipoprotein concentration 60 micrograms protein/ml. Lipoprotein-mediated reduction in the number of [3H]dexamethasone binding sites resulted in partial loss of cellular sensitivity to hormone action: dexamethasone (1 x 10(-6) M) inhibited the transformation of [14C]arachidonic acid (AA) into metabolites to a lesser extent in SMC preincubated with VLDL (11.5%) than in untreated cells (29.0%). In particular, under these conditions the inhibitory effect of dexamethasone on prostaglandin I2 (PGI2) formation in VLDL-treated SMC was lower than in untreated cells (42.1% vs. 60%). We propose that VLDL is able to counteract the inhibitory effect of glucocorticoids on AA release and PGI2 formation in vascular SMC by reduction of cellular specific glucocorticoid binding sites. PMID- 8443236 TI - Involvement of tyrosine kinase in growth factor-induced phospholipase C activation in NIH3T3 cells. AB - Tyrosine kinase inhibitors such as erbstatin and lavendustin derivative inhibited platelet-derived growth factor (PDGF)- and bombesin-induced inositol phosphate formation and phospholipase C (PLC) activation in quiescent NIH3T3 cells. However, bombesin-induced PLC activation was only partially inhibited by tyrosine kinase inhibitors, whereas PDGF-induced activation was completely. Moreover, although bombesin-induced PLC activation was partially inhibited by pertussis toxin alone, this toxin inhibited almost completely in the presence of tyrosine kinase inhibitors. Thus, tyrosine kinase was suggested to be involved in PDGF- and bombesin-induced PLC activation in a different manner. PMID- 8443237 TI - Desaturation and chain elongation of n - 3 and n - 6 polyunsaturated fatty acids in the human CaCo-2 cell line. AB - Human CaCo-2 cells were incubated with [14C]linoleic (18:2(n - 6)), [14C]linolenic (18:3(n - 3)) and [3H]eicosapentaenoic acid (20:5(n - 3)), and the interconversion of the radioactive fatty acids to higher homologues and their acylation into triacylglycerols (TG) and phospholipids were examined. An active conversion of [14C]18:3 to [14C]20:5 and [14C]docosapentaenoic acid (22:5(n - 3)) and of [3H]20:5 to [3H]22:5, but not to [3H]docosahexaenoic acid (22:6(n - 3)) was observed. In relation to the amounts that had been incorporated into cellular phospholipids and TG, the interconversion of [14C]18:3 clearly exceeded that of [14C]18:2. Addition of 10-100 microM 18:2 or 10-50 microM arachidonic acid (20:4(n - 6)) increased the percent interconversion of [14C]18:2 to [14C]20:4. E.g., addition of 50 microM 20:4 increased the formation of [14C]20:4 from 4.4 +/ 0.1% to 5.9 +/- 0.8%, decreased the incorporation into phospholipids from 64.8 +/- 6.3% to 31.4 +/- 1.2% and increased the incorporation into TG from 8.8 +/- 0.4% to 28.8 +/- 1.1%. In contrast, addition of 10-100 microM 18:3 or 20:5 significantly decreased the interconversion of both [14C]18:2 and [14C]18:3. E.g., addition of 50 microM 20:5 decreased the formation of [14C]20:4 from [14C]18:2 from 4.4 +/- 0.1% to 0.9 +/- 0.1%, whereas the effects on the acylation reactions were very similar to those of 20:4. 20:5 also decreased the formation of interconversion products from [14C]18:3. 18:2 and 20:4 caused a smaller decrease in the formation of [14C]20:5 and actually increased percent conversion to [14C]22:5. The percent conversion of [3H]20:5 to [3H]22:5 was also increased by the addition of 50-100 microM unlabeled 20:5. [14C]18:2 and [14C]18:3 were predominantly incorporated into phosphatidylcholine (PC) whereas more of the radioactive 20:4, 20:5 and 22:5 was incorporated into phosphatidylethanolamine (PE). An active fatty acid interconversion catalyzed by delta 6 and delta 5 desaturases thus occurs in the human CaCo-2 cell line, whereas conversion of 20:5(n - 3) to 22:6(n - 3) could not be demonstrated. The desaturation-elongation pathway has a preference for 18:3(n - 3) and is subjected to an efficient feedback regulation by 20:5(n - 3). Formation of 22:5 increases with available 20:5 mass and by the presence of other polyunsaturated fatty acids competing with 20:5 for acylation into phospholipids. PMID- 8443238 TI - Structural and functional properties of natural and chemical variants of apolipoprotein A-I. AB - Four isoforms of human apolipoprotein A-I (apo A-I): the normal allele product and the corresponding Lys-107 deletion mutant, and apo A-I with sulfoxidized Met 112 and Met-148 residues and the corresponding reduced form, were investigated in their lipid binding properties, structures, and abilities to activate lecithin cholesterol acyltransferase. All apo A-I isoforms reacted completely with palmitoyloleoylphosphatidylcholine to give reconstituted high density lipoprotein (rHDL) particles with diameters of 96 A. These particles reacted with low density lipoprotein (LDL) and lecithin-cholesterol acyltransferase (LCAT) equally well, except that the Lys-107 deletion mutant was resistant to structural rearrangements in the presence of LDL. The spectral measurements revealed only minor structural differences among the free apo A-I forms or among their rHDL products, but showed a decreased stability of the Lys-107 deletion mutant and the isoform with reduced Met towards denaturation by guanidine hydrochloride. The results demonstrate that these specific alterations of the apo A-I sequence, which change the helix orientation and hydrophobic moment in one or two putative lipid binding regions, are not sufficient to disrupt the overall properties of the apo A-I complexes with lipid nor to impair significantly their ability to activate LCAT. PMID- 8443239 TI - Induction of cyclooxygenase and suppression of 12-lipoxygenase in human erythroleukemia cells upon phorbol ester-induced differentiation. AB - When human erythroleukemia (HEL) cells were incubated with arachidonic acid, both fatty acid cyclooxygenase and arachidonate 12-lipoxygenase activities were exhibited. Subcellular localization of these enzymes were examined by differential centrifugation, and both the cyclooxygenase and the 12-lipoxygenase were present predominantly in the microsomes rather than the cytosol of the cells. The cyclooxygenase activity was stimulated by 12-O-tetradecanoylphorbol 13 acetate (TPA) in a dose-dependent and time-dependent manner. Actual increase in the cyclooxygenase protein by TPA was demonstrated by immunoprecipitation and Western blot analysis of the enzyme with the aid of an anti-cyclooxygenase antibody. Furthermore, the cyclooxygenase mRNA level increased as assessed by RNA blot analysis using a cDNA probe for the enzyme. In contrast, the TPA treatment reduced the activity of 12-lipoxygenase. By RNA blot analysis using a cDNA probe of HEL cell 12-lipoxygenase, the mRNA level of the enzyme was shown to decline by the TPA treatment. Taken together, the TPA treatment of HEL cells brought about the induction of cyclooxygenase and the suppression of 12-lipoxygenase. PMID- 8443240 TI - Biosynthesis and characterization of phosphatidylglycerophosphoglycerol, a possible intermediate in lipoteichoic acid biosynthesis in Streptococcus sanguis. AB - A membrane enzyme preparation from Streptococcus sanguis was shown to convert sn [14C]glycerol 3-phosphate and CDP-diacylglycerol (or deoxyCDP-diacylglycerol) into a series of progressively higher-molecular-weight [14C]oligophosphoglycerophospholipids in vitro. The first oligophosphoglycerophospholipid to accumulate (termed lipid-1) was purified to homogeneity; chemical analysis, gas-liquid chromatography and chemical degradation studies indicated the most likely structure to be phosphatidylglycerophosphoglycerol (PGpG). PGpG is formed directly from two molecules of phosphatidylglycerol (PG), one molecule of PG serving as a sn glycerol 1-phosphate (pG) donor and the second serving as the pG acceptor, with co-production of diacylglycerol. These oligophosphoglycerophospholipids may be intermediates in the biosynthesis of lipoteichoic acids. PMID- 8443241 TI - Simultaneous changes in lipid composition, fluidity and enzyme activity in piglet intestinal brush border membrane as affected by dietary polyunsaturated fatty acid deficiency. AB - The effects of dietary polyunsaturated fatty acid (PUFA) deficiency on intestinal brush border membrane (BBM) fluidity, lipid composition and 5'-nucleotidase activity were examined in piglets. Cholesterol/phospholipid and sphingomyelin (SM)/phosphatidylcholine (PC) ratios were unaffected. However, fluidity was decreased in the external regions and also tended to decrease in the core of the PUFA-deficient pig membrane lipid bilayer. Therefore, the change in the membrane physical properties seemed to be due to the large diet-induced alteration in the phospholipid (PL) fatty acid composition and to the concomitant decrease in PC and increase in phosphatidylserine levels. In the membrane total PL, the arachidonic acid level was slightly lowered, while linoleic, eicosapentaenoic and docosahexaenoic acid levels markedly decreased. PC was mainly concerned by the altered distribution of unsaturated fatty acids, but not SM. However, a significant decrease in (n-6)/(n-3) ratio occurred in the latter. These structural changes were associated with a higher 5'-nucleotidase activity in the intestinal BBM of PUFA-deficient as compared to control piglets. PMID- 8443242 TI - Cholesterol feeding induces hypertriglyceridaemia in hamsters and increases the activity of the Mg(2+)-dependent phosphatidate phosphohydrolase in the liver. AB - (1) Feeding increased cholesterol to hamsters resulted in a dose-dependent increase in cholesterol and triacylglycerol in very-low-density lipoprotein (VLDL), in serum non-esterified fatty acids and in the activity of the Mg(2+) dependent phosphatidate phosphohydrolase in liver. (2) The effects of increasing dietary cholesterol by 0.12% (w/w) in addition to feeding fat (14%, w/w) were dependent upon the nature of the fat. Lard in the presence of 0.12% (w/w) cholesterol increased serum triacylglycerols as did olive oil. By contrast, sunflower oil did not cause a significant change in serum triacylglycerol concentrations. (3) There was a highly positive correlation between VLDL triacylglycerol and VLDL cholesterol concentrations suggesting that, at least in this model, there is a close relationship between hypertriglyceridaemia and hypercholesterolaemia. PMID- 8443243 TI - Simplified methods for the synthesis of 2-hexadecanoylthio-1 ethylphosphorylcholine and for the determination of phospholipase A2 activity. AB - A simple and straight forward method was developed for the synthesis of 2 hexadecanoylthio-1-ethyl phosphorylcholine (HEPC). The new procedure, which used p-toulenesulfonate instead of 2-bromoethyl phosphorylcholine, not only reduced the reaction time but also allowed the reaction to proceed under mild conditions. Using HEPC as a substrate, we have also developed a microplate assay for measuring phospholipase A2 activity which is rapid and will be useful for analyzing a large number of samples in a very short time. The applicability of this assay method for assessing phospholipases A2 from two different sources and determining their kinetic constants is also demonstrated. This method can also be extended for measuring lipases and lysophospholipases using a suitable thioester. Thus, both synthesis and assay methods will be useful in basic and applied research on phospholipases and related enzymes. PMID- 8443244 TI - Synthesis of phosphatidylcholine in guinea-pig fetal lung involves acyl remodelling and differential turnover of individual molecular species. AB - The mechanisms for accumulation of disaturated phosphatidylcholine (PC) molecular species in developing fetal guinea-pig lung during the period of surfactant synthesis, between day (d) 55 and term (d68), were determined by the incorporation of 50 mu Ci [methyl-14C]choline into lung PC in utero over 3 h. Comparison of the pattern of PC synthesis de novo with the composition of the total PC pool indicated that approx. 50% of the total PC16:0/16:0 was synthesized by acyl remodelling of PC16:0/18:2 by the actions of phospholipase A2 and acyltransferases. Acyl remodelling was established before the onset of surfactant synthesis (d55) and so was not specific for this process. Between d55 and term the concentration of lung PC increased significantly. Conversely, the incorporation of [14C]choline into lung tissue and the rate of PC synthesis decreased over this period. Calculation of turnover times of lung PC species suggested that the increase in lung disaturated PC concentration during surfactant production might be due to a differential decrease in catabolism rather than increased PC synthesis. PMID- 8443245 TI - bis-Allylic hydroxylation of linoleic acid and arachidonic acid by human hepatic monooxygenases. AB - [14C]Linoleic acid was incubated with human liver microsomes and NADPH and biosynthesis of allylic hydroxy fatty acids was investigated. 11-Hydroxy-9Z,12Z octadecadienoic acid (11-HODE), 9-hydroxy-10E,12Z-octadecadienoic acid (9-HODE), 13-hydroxy-9Z,11E-octadecadienoic acid (13-HODE) and 14-hydroxy-9Z,12Z octadecadienoic acid were identified. 9-HODE and 13-HODE were formed with stereoselectivity (80% R) provided that 11-HODE was prevented from decomposing to 9(R,S)-HODE and 13(R,S)-HODE by extractive isolation at pH 5-6. Human hepatic microsomes metabolized [14C]arachidonic acid to many products, including 13-HETE and small amounts of 15-HETE (> 90% R), 11-HETE (59% R) and 12-HETE (> 90% R). Hepatic microsomes of untreated rats metabolized [14C]linoleic acid to 11-HODE as a major product, but significant formation of 11-HODE by purified cytochrome P 450 (P450) (CYP1A1, CYP2B1, CYP2B4, CYP2E1, CYP3A6 and CYP4A1) in a reconstituted system could not be detected, indicating that 11-HODE might be formed by other and constitutive P450 isozymes. PMID- 8443246 TI - Formation of platelet-activating factor-like phospholipids by Fe2+/ascorbate/EDTA induced lipid peroxidation. AB - We have identified novel phospholipids together with platelet-activating factor and its 1-acyl analogues in purified fractions from a bovine brain lipid extract. These novel compounds were phospholipids with an sn-2-short-chain monocarboxylyl, dicarboxylyl or omega-hydroxymonocarboxylyl group. The profiles of these three types of phospholipids suggest that they were formed by lipid peroxidation. To examine this possibility, we peroxidized synthetic phosphatidylcholines (PC) with an sn-2-polyunsaturated fatty acyl group and PC from bovine brain, with Fe2+/ascorbate/EDTA, and analyzed the secondary degradation products retaining a glycerol backbone by fast atom bombardment-mass spectrometry and GC-MS. Results showed the formation of four kinds of PC with a short-chain monocarboxylate, dicarboxylate, dicarboxylate semialdehyde or omega-hydroxymonocarboxylate moiety. The chain lengths of these PC were related to the position of the double bond vicinal to the esterified carbonyl group in the sn-2-long-chain acyl moiety of the parent PC. The molecular heterogeneity of secondary products formed by the oxidative degradation of bovine brain PC resembled those of the unique phospholipids that we previously detected in the fractions with platelet activating factor-like activity purified from a bovine brain lipid extract, although the former lacked the species with an acetyl group. These results suggest that all the novel phospholipids with a short-chain acyl group in the brain lipid extract except that with an acetyl group were produced by lipid peroxidation. PMID- 8443247 TI - Selective association of lipoprotein cholesteryl esters with liver plasma membranes. AB - High-density lipoprotein (HDL) cholesteryl esters are taken up by hepatocytes without parallel uptake of HDL apolipoproteins. This selective uptake of HDL cholesteryl esters is mediated by a non-endocytotic mechanism. Recently, selective uptake of cholesteryl esters also from low-density lipoprotein (LDL) was demonstrated. In this study, the role of the plasma membrane in selective uptake by the liver was investigated. Plasma membranes were prepared from rat liver or from human Hep G2 hepatoma cells. Human HDL3 (d = 1.125-1.21 g/ml) was either radioiodinated or labeled with [3H]cholesteryl oleate. Human low-density lipoprotein (d = 1.019-1.05 g/ml) was labeled in its protein and in its lipid moiety as well. Labeled lipoproteins, unlabeled lipoproteins and membranes were incubated. After separation by ultracentrifugation, apparent lipoprotein particle association with membranes was determined. Plasma membranes from rat liver and Hep G2 cells bound 125I-HDL3, indicating specific HDL3 particle binding. With both types of membrane, apparent HDL3 particle association according to [3H]cholesteryl oleate-labeled HDL3 was in significant excess on that due to 125I HDL3. This indicates selective, i.e., particle binding independent, association of cholesteryl esters with the membrane. Excess unlabeled HDL3 competed for selective association, indicating a specific process. Selective association of HDL3 cholesteryl esters was concentration-, time-, temperature-dependent; however, parameters differed from HDL3 particle binding. HDL3 was modified by nitration; this modification inhibited HDL3 particle binding in contrast to unchanged selective association. These results suggested distinct membrane sites for HDL3 particle binding and selective cholesteryl ester association. Regulation of selective association was investigated. Hep G2 cells were cholesterol-loaded or cholesterol-depleted. Cellular cholesterol-loading down-regulated selective association of HDL3 cholesteryl esters with isolated membranes prepared from these cells. In parallel, selective uptake of HDL3 cholesteryl esters by Hep G2 cells was down-regulated in cholesterol-loaded cells. This parallel regulation of selective association with membranes and selective uptake by cells suggests a functional relationship. LDL, radiolabeled in its protein and in its lipid moiety, was incubated with liver plasma membranes. Besides LDL holo-particle receptor binding, also LDL cholesteryl esters were selectively associated with membranes. These data showed that selective association with membranes is not restricted to HDL but can occur from LDL as well. It is concluded that HDL3 as well as LDL cholesteryl esters can selectively be associated with hepatic plasma membranes, i.e., independent from particle binding. Results suggest an important role of the plasma membrane in the mechanism of selective cholesteryl ester uptake by the liver. PMID- 8443248 TI - Lecithin-cholesterol acyltransferase: effects of mutagenesis at N-linked oligosaccharide attachment sites on acyl acceptor specificity. AB - Site-directed mutagenesis was used to generate lecithin-cholesterol acyltransferase (LCAT) species in which individual attachment sites for N-linked oligosaccharide residues were replaced with residues that prevent the attachment of carbohydrate. Mutants at three of four sites retained significant acyltransferase activity, and phospholipase activity in the absence of cholesterol. Mutation at one site (asn272) converted LCAT to a phospholipase generating fatty acids not cholesteryl esters. PMID- 8443249 TI - Monensin inhibits synthesis of plasma membrane sphingomyelin by blocking transport of ceramide through the Golgi: evidence for two sites of sphingomyelin synthesis in BHK cells. AB - The monovalent cationophore monensin, which is known to interfere with vesicular transport through the Golgi apparatus, inhibits synthesis of sphingomyelin in BHK cells by up to 40%. The monensin-sensitive component of sphingomyelin synthesis appears to be the pool which normally reaches the cell surface since treatment of cells with exogenous sphingomyelinase causes an almost identical loss of sphingomyelin. Monensin causes increases in ceramide and glucosylceramide labelling which together are equivalent to the decrease in sphingomyelin labelling. Monensin also increases synthesis of cholesterol ester, probably due to the decreased delivery of sphingomyelin to the plasma membrane. However, monensin has no effect on resynthesis of plasma membrane sphingomyelin which has been degraded by extracellular sphingomyelinase. The results support the idea that synthesis of sphingomyelin destined for the plasma membrane does not occur in the cis- or medial-Golgi but depends on vesicular transport of ceramide to a second synthesis site which is distal to the medial-Golgi. PMID- 8443251 TI - Vocational rehabilitation for persons with arthritis and musculoskeletal disorders: fact or fantasy? PMID- 8443250 TI - Cholesterol uptake in the human intestine. Hypo- and hyperresponsiveness. AB - Cholesterol uptake was studied at the small intestine biopsies taken from patients without intestinal malfunction. Three distinct groups of patients were described: those with low (146 +/- 19) nmol/mm2 per 2 h), medium (455 +/- 18 nmol/mm2 per 2 h) and high (833 +/- 24 nmol/mm2 per 2 h) rates of cholesterol uptake. Positive correlation between cholesterol uptake and intestinal cholesterol synthesis was observed in the last two groups. PMID- 8443252 TI - Effect of a walking program on gait characteristics in patients with osteoarthritis. AB - This paper reports the results of a study of the gait of 102 patients with osteoarthritis of the knee. Functional status was measured by a 6-min test of walking distance; the stride characteristics associated with the walk test were assessed. Stride characteristics were measured by a Stride Analyzer. Patients were randomized to an 8-week educational and walking program (the intervention group) or to a weekly telephone survey (the control group). The intervention group patients had a 15% increase in walking distance (P < 0.0001) and increases of 9.1% in stride length at free walking speeds (P < 0.007) and 17% in stride length at fast walking speeds (P < 0.01) compared to the control group. The results of this study have shown that the walking and educational program was effective in improving gait function in patients with osteoarthritis of the knee. PMID- 8443254 TI - Medical and psychosocial predictors of sexual outcome among women with systemic lupus erythematosus. AB - The influence of medical and psychosocial variables on sexual outcome in 100 women with systemic lupus erythematosus was examined. Subjects were administered a sexual adjustment interview and scales assessing depression, body image, and relationship quality. Medical data were obtained from patients and physicians. Key predictors of sexual outcome were disease severity (P < 0.001), premorbid sexual adjustment (P < 0.05), and relationship quality (P < 0.05). Results suggest that the impact of systemic lupus erythematosus on sexual response may best be understood by considering a combination of interpersonal, psychological, and medical conditions in a patient's life. PMID- 8443253 TI - Self-management of osteoarthritis. AB - Osteoarthritis is the most prevalent activity-limiting condition among older persons. In addition to, or instead of, taking nonsteroidal anti-inflammatory drugs, people use a variety of activities to manage their osteoarthritis. This study describes the self-management methods reported by 61 participants aged 60 years or older assessed on two occasions 8 months apart. A questionnaire was developed to assess levels of use of 10 self-management methods including low impact activity, rest, range-of-motion exercises, relaxation, heat (or cold), taking medication, joint protection, massage, splints, and any other activity. On a typical day, participants used about four of these activities to manage osteoarthritis symptoms, and significantly more on a day that their arthritis was worse than usual. Three self-management scales were formed from groups of activities suggested by factor analysis (medication taking, typical management, and worse-day passive management) that demonstrated adequate internal consistency and stability across the two assessments. The findings are discussed in terms of the importance of developing a brief measure of osteoarthritis self-management, and the substantial individual variation in subsets of methods used. PMID- 8443255 TI - Comparison of selected health behavior variables in elderly women with osteoarthritis in different environments. AB - Hardiness, social support, perceived health, functional independence, and use of health care facilities were compared in this descriptive study of 45 elderly women with osteoarthritis living in three different environments--urban, rural, and frontier. All participants were between the ages of 65 and 75 years and were residing in their own homes. Statistical differences were found between groups in overall perceived health and functional independence; the frontier sample perceived their health as better and themselves as more functionally independent than the urban or the rural sample. No statistical differences were found in levels of hardiness or perceived social support between the three groups. Use of health care facilities varied among participant groups by environmental context; the urban group made more use of facilities than the rural or frontier group, and the rural group used more facilities than the frontier group. PMID- 8443256 TI - Effect of counselor training on skills development and psychosocial status of volunteers with systemic lupus erythematosus. AB - Volunteers with systemic lupus erythematosus were recruited for a telephone service to provide psychosocial support to peers. The volunteers attended an 8 week counselor training program. The aim was to evaluate the impact of the training on counselors' skill development and to record possible changes in the counselors' psychosocial status. A second group of trainees (n = 15) was used as a delayed control for the first group (n = 14). The data were analyzed using multivariate repeated measures analysis of variance. Tests chosen to monitor psychosocial status included: Arthritis Impact Measurement Scales Anxiety and Depression subscales, Arthritis Helplessness Index, Wallston General Self Efficacy Scale, University of California at Los Angeles Loneliness Scale, Rosenberg Self-Esteem, and Campbell Personal Competence scales. Tests selected to measure skills and knowledge. PMID- 8443257 TI - Dietary intake and circulating vitamin levels of rheumatoid arthritis patients treated with methotrexate. AB - The nutrient intakes and circulating vitamin levels of 32 patients with rheumatoid arthritis who were treated with methotrexate were evaluated over a 6 month period. Dietary data were obtained and blood was drawn prior to the initiation of and following 12 and 24 weeks of methotrexate therapy. More than 50% of the patients had food intakes providing less than 67% of the recommended dietary allowance for zinc, vitamin E, folic acid, pyridoxine, and magnesium. Patients 51 years or older had better nutrient intakes than patients less than 51 years. Of the patients, 22% consumed vitamin supplements at the time they were recruited for the study. Mean circulating vitamin levels measured over the 6 month period were within normal limits. Our findings agree with previously published reports that patients with rheumatoid arthritis, particularly the subpopulation taking methotrexate, consume diets that are marginal in some nutrients. Additional research needs to be done to identify more sensitive nutrient assays and to establish more definitively the nutrient needs of patients with rheumatoid arthritis taking several therapeutic agents. PMID- 8443258 TI - Gender, depression, and ankylosing spondylitis. AB - Depression has been established as a common reaction to rheumatoid arthritis but has rarely been investigated among people with other forms of arthritis. The present study examined the prevalence and determinants of depressive symptoms in people with ankylosing spondylitis, focusing on gender differences and set in the context of widely held medical views concerning the psychosocial nature of ankylosing spondylitis patients. Results showed that approximately one third of the ankylosing spondylitis patients reported a high level of depressive symptoms and that women reported more depression than men. No evidence was found to support the stereotype of the "typical" ankylosing spondylitis patient as being less depressed than people with other forms of arthritis. Pain was found to be a major determinant of depression for women, but was of lesser importance for men. The implications of these findings are discussed. PMID- 8443259 TI - The effect of isometric quadriceps strength training in mid-range for osteoarthritis of the knee. AB - This case report describes the effect of strengthening the quadriceps of an effused osteoarthritic knee joint of a 53-year-old man isometrically in mid range. The instruments included an isokinetic dynamometer, a knee scoring inventory, and a visual analog scale. The outcome measures of isometric quadriceps torque and work, clinical status, and pain were recorded before and after the exercise intervention. The exercises were carried out three times per week for a 6-week period with the subject seated on an exercise chair. Following training, quadriceps torque increased, clinical status improved, and pain with walking decreased. Subject to further investigation, isometric training of the quadriceps in mid-range could prove useful for improving the function of persons with painful or effused knees who might otherwise experience muscle inhibition by exercising in the more traditional inner ranges of knee extension. PMID- 8443260 TI - Delegation: getting results through others. PMID- 8443261 TI - Nursing's collective voice being heard. PMID- 8443262 TI - Inflammatory bowel disease impact and patient characteristics. AB - A major purpose of this survey was to describe the impact of inflammatory bowel disease on the daily life of 150 nonhospitalized adults. A complementary purpose was to examine patient characteristics and their relationship to perceived impact. Self-report questionnaires and interviews were used to collect the data. Most patients reported a low to moderate impact of the disease on daily life. Greatest impact was reported in the areas of elimination, worry, recreation and leisure activities, sleep and rest. Among patient characteristics that correlated positively with the impact variable were age, under 35 years, female gender, depressed mood, and affective-oriented coping style. The findings suggest that nurses and other health professionals may enhance patient adaptation and life satisfaction by focusing efforts on patient characteristics that are amenable to change and on areas of life where the disease impact is experienced most intensively. PMID- 8443263 TI - Clinical pharmacology of commonly used drugs in GI practice. Part II. AB - In Part I of this series of articles on clinical pharmacology of commonly used drugs in GI practice, drugs used in the GI laboratory, as adjuncts to endoscopic premedication, and as antibiotic prophylaxis for infective endocarditis and complications of endoscopy were presented. In Part II, drugs used in the management of peptic ulcer disease (antacids, H-2 receptor and proton pump antagonists), pancreatic enzymes, prokinetic agents, and drugs used with inflammatory bowel disease are described. PMID- 8443264 TI - Accurate data: the basis of decision. AB - This article provides an overview of the process for obtaining accurate data. Information about organizing data collection, managing data, and communicating findings is given to assist nurses in developing and evaluating data used in practice and clinical nursing research. PMID- 8443265 TI - Dietary management of chronic diarrhea in children. AB - This study evaluated the benefit of a gastroenterology nurse clinician providing dietary instructions to parents of children with recurrent diarrhea. These instructions for returning the child to a normal age-appropriate diet were given by telephone at the time of referral. Data analysis indicated that parents reported a decreased number of stools and an improved stool consistency during the waiting period for a clinic appointment, regardless of whether or not they received dietary instructions. Children in the control group lost an average of 0.4 g/day of weight while those whose parents received dietary instructions gained an average of 1.57 g/day. This difference in weight is clinically important and reinforces the premise that children with chronic diarrhea often receive calorie-deficient diets. The results of this study emphasize the important role that gastroenterology nurses play in the management of chronic diarrhea in children. PMID- 8443266 TI - Flagyl (metronidazole hydrochloride). AB - Flagyl (metronidazole) is an anti-infective agent used in the treatment of anaerobic bacteria and protozoa. The most common uses of Flagyl in the patient undergoing gastroenterology evaluation and interventions are generally for anaerobic invasion of the gastrointestinal tract causing conditions such as giardiasis. Flagyl is also commonly used in the preoperative treatment of patients prior to colorectal surgery or those at high risk for bacterial contamination during the operative intervention (e.g., patients having emergency abdominal surgery with an unprepared colon). Flagyl is a highly potent anti infective agent that must be administered and monitored appropriately for safe and effective use. PMID- 8443267 TI - [Peripheral parenteral nutrition: myth or reality?]. AB - In the changing world of parenteral nutrition, daily doubts about methods arise which are not easily resolved. Controversy thus occurs on conceptual changes in energy requirements according to different levels of aggression, or as to the different utilisation of nutrients according to aggression, or referred to the most effective relations between energy and plastic substrates or the indication of and maintenance time for perioperative parenteral nutrition. While all these questions remain alive, recent years have seen the addition of a further polemical subject: is hypocalorific peripheral parenteral nutrition effective as nutritional backup for surgical patients? What are its indications and limitations? Answers to these questions require in the first place the establishment of criteria which clarify concepts that may not always be used precisely, perhaps due to their indiscriminate application (perioperative, peripheral, hypocalorific nutrition, etc.) After reviewing the physiological basis for this type of backup, we then make an evaluation of the effects of perioperative parenteral nutrition in terms of the evolution of the illness, before making a critical analysis of a variety of studies carried out by different writers, in an attempt to extract common conclusions from the diverse results on the efficacy of this type of nutritional backup. PMID- 8443268 TI - [Liver dysfunction associated with total parenteral nutrition]. AB - An evaluation is made of liver malfunctions in patients receiving TPN over a period of > or = 15 days between 1989 and 1991. Use was made of the monitoring records on patients undergoing TPN and, subsequently, of clinical records, with analysis of diagnoses and type of intervention, the biochemical parameters (SGOT, SGPT, GGT, FA, LDH, and total and direct bilirubin), and the type and degree of malnutrition, nutritional backup, associated medication, etc. A group of patients was excluded from the study on the basis of the following criteria: liver-biliary disease, cardiac insufficiency, liver metastasis, sepsis, kidney insufficiency and hepatotoxic drugs. Of 237 patients, 75 (31.64%) had liver alterations: following application of the exclusion criteria, 24 patients (10.12%) were taken with liver alterations attributable to the TPN. Macro- and micronutrients were included in the TPN. We found no relation between the kcal/kg of weight, nor with the quantity of glucose and fats nor of nitrogen, calculated according to individual requirements: they remained within the limits established. No serious case of cholestatic jaundice was encountered. Moderate to severe malnutrition was found in 50% of patients, so that this must be treated as a risk factor. GGT is the first enzyme to alter; this occurred in the largest proportion of patients (91.66%), followed by SGPT. FA and GOT are altered in the same percentage of patients. Biochemical parameter monitoring is essential in patients undergoing TPN, not only for appraisal of the nutritional state but also to prevent or correct potential serious metabolic complications. PMID- 8443269 TI - [The stability of antibiotics administered in and with a parenteral nutrition mixture enriched with branched-chain amino acids. I. Amikacin and gentamycin]. AB - The combined infusion of antibiotics and parenteral nutrition makes it possible to maintain plasmatic nutrient concentrations over time, in turn facilitating the administration of the antibiotics in the dilution and infusion time recommended according to their pharmacokinetic parameters. On the other hand, this type of administration has care benefits for the patient, reducing the risk of infections, and adding to comfort. The technique is also cost-effective, reducing the cost of drug administration, saving on administrative personnel and nursing staff time. The stability of amikacin and gentamicin are determined in vitro at therapeutic concentrations jointly infused with a mixture of parenteral nutrition with polyols and enriched in ramified chain amino acids. A microbiological stability analysis was carried out of the antibiotics in the parenteral nutrition, along with an HPLC aminogram, in order to determine the concentration of amino acids in the combined infusion with the antibiotic. pH measurements were also taken, along with osmolarity and colour change. Both of the antibiotics and the parenteral nutrition employed, and of the combined infusion mixtures. Amikacin and Gentamicin are stable at a concentration of 5 mg/ml and 1.6 mg/ml respectively in a parenteral nutrition mixture enriched in ramified chain amino acids. PMID- 8443270 TI - [Cardiac tamponade: a fatal complication of parenteral nutrition]. AB - Several complications are associated with the use of central venous catheters for total parenteral nutrition; cardiac tamponade is one of the most severe. The recent use of flexible materials made of silastic polymeric silicone has great decreased the incidence of this complication, but has not eliminated wholly. We report the case of a patient with fatal cardiac tamponade, while receiving parenteral hyperalimentation trough a silicone central venous catheter placed in the right jugular internal vein, secondary to superior vena cava perforation. The physiopathological mechanisms, precautionary measures and treatment are discussed. PMID- 8443271 TI - [The selection of the indicators for a quality control policy in parenteral nutrition starting from clinical follow-up]. AB - INTRODUCTION: the concept of quality is basic to any type of clinical/care activity and with parenteral nutrition (NP), the notion is of particular significance in the field of its clinical monitoring. The aim of this paper is to reveal the NP care level based on our experience in clinical monitoring in 1988, and to select the indicators to be evaluated for initiating NP quality control. MATERIAL AND METHODS: An analysis is made of the existing structure in our hospital, formed by the NP Unit and the NP and Enteral Nutrition Commission, which are subject to a policy of coordination in order to ensure their function. The process is divided into two aspects for the analysis - teaching and care. The clinical monitoring data of NP patients in 1988 were taken as reference in defining the indicators. RESULTS: The indices are presented which were obtained from the analysis of the data of a general nature, from an assessment of the degree of compliance with the procedure, and from the quantification of complications and the indicators elected as quality parameters. DISCUSSION: Although the clinical monitoring of the PN began with the general wish to evaluate different aspects associated with nutritional therapy, this focus later evolved toward the notion of quality. Not all the data gathered during the clinical monitoring can be taken as quality criteria: only those deemed to be more relevant, or of greater clinical significance, and which can be reliably measured, can be treated thus. PMID- 8443272 TI - [Sepsis due to multiple-lumen catheters in bone marrow transplantation with total parenteral nutrition. The effect of the type of isolation]. AB - The use of catheters for total parenteral nutrition frequently leads to infectious complications which are more common and virulent in patients with marrow aplasia. The main purpose of this paper was to evaluate the influence in the development of catheter-induced sepsis of the place where it was introduced (in the theatre or hospitalization unit), the type of isolation (laminar flux unit or conventional room), and its relation to the period of isolation and of the total parenteral nutrition. Forty-one bone-marrow transplant patients were studied, 18 of them autologous and 23 allogenic, who were administered total parenteral nutrition with a two-way central venous polyurethane catheter. Of the 41 catheters applied, 16 were introduced in the operating theater and 25 in the hospitalization unit: of these, 7 and 11 respectively were infected. Isolation was as follows: 21 in standard rooms and 20 in a laminar flux unit, with 11 and 7 infections respectively. We believe that the lower level of infections in laminar flux isolation was not significant, this being a reduced number of case studies. The duration of the catheter and total parenteral nutrition for the 18 patients with sepsis was 36.5 +/- 15.1 and 23.7 +/- 8.4 days respectively: this was greater--albeit possibly not significantly so because of the special characteristics of these patients--than the 29.1 +/- 12.9 and 19.5 +/- 10.9 days for non-septic cases. This reveals a catheter sepsis rate of 43.9%, in 88% of cases caused by skin flora micro-organisms (66.6% coagulase-negative staphylococcus).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8443273 TI - Peritoneal dialysis-related peritonitis treatment recommendations. 1993 update. The Ad Hoc Advisory Committee on Peritonitis Management. International Society for Peritoneal Dialysis. AB - In conclusion, the recommendations provided in this document represent a distillation of various experiences, as well as data obtained from published studies. It is hoped that this compilation will provide a basis upon which future developments and advances can be made in the therapeutic approach to infectious complications of peritoneal dialysis. PMID- 8443274 TI - Peritoneal catheters and exit-site practices: toward optimum peritoneal access. AB - The peritoneal catheter is the CAPD patient's lifeline. Advances in catheter knowledge have made it possible to access the peritoneal cavity safely and maintain access over an extended period of time. Infection at the exit site remains a major problem, a solution for which is being extensively researched. The successful outcome of a catheter in an individual depends on meticulous care and adherence to sound principles of catheter insertion and management. The guidelines provided in this publication represent the consensus based on the extensive experience of several major centers worldwide. PMID- 8443275 TI - Effective continuous ambulatory peritoneal dialysis following abdominal aortic aneurysm repair. AB - OBJECTIVE: To review a single center's experience with the initiation and maintenance of continuous ambulatory peritoneal dialysis (CAPD) in 8 patients with a history of abdominal aortic aneurysm repair (AAAR). DESIGN: Retrospective case review with long-term follow-up. PATIENTS (OR PARTICIPANTS): Eight patients with multiple medical problems including a history of abdominal aortic aneurysm repair and end-stage renal failure who received peritoneal dialysis catheters between December 1986 and July 1991. MAIN OUTCOME MEASURES: Success of catheter implantation and maintenance of continuous ambulatory peritoneal dialysis; incidence of peritoneal infection and long-term complications; overall clinical course. RESULTS: Over five years 8 patients with a history of reconstructed abdominal aortic aneurysm received peritoneal dialysis catheters without complication and dialyzed successfully for 88 patient-months in total. Three patients had a total of five episodes of peritonitis, at an incidence of 0.68 episodes per patient per year, a rate not significantly different from that of our overall CAPD patient population (1.09) and that reported by other groups. CONCLUSION: Our experience suggests that historical AAAR poses no significant risk to and should not preclude the implementation of continuous ambulatory peritoneal dialysis. Indeed, CAPD offers a safe and optimal dialytic alternative for patients with historical abdominal aortic aneurysm repair in whom compromised cardiovascular hemodynamics may significantly influence morbidity and survival. PMID- 8443276 TI - A comparison of peritoneal dialysis-related infections in black and white patients. AB - OBJECTIVE: To determine if black patients in our peritoneal dialysis (PD) program had higher rates of PD-related infections. The outcomes of black patients versus white patients were also reviewed. DESIGN: A review of prospectively collected patient demographic and PD-related infection data and outcomes, from 1979 to 1991. PATIENTS: The 68 black patients in our PD program were matched with white control patients for age, sex, insulin dependence, time on dialysis, and mode of dialysis (CAPD or CCPD). The infection, demographic, and outcome data from the two groups were compared. RESULTS: Black patients had higher peritonitis rates (1.10 vs 0.82 episodes/year, p = 0.001) and exit-site infection rates (1.13 vs 0.95 episodes/year, p = 0.02) than the white control patients. Tunnel infection rates were 0.21 episodes/year in both groups. S. epidermidis peritonitis was more common in black patients (48% of episodes vs 21% of episodes in whites, p = 0.005), and S. aureus peritonitis was more common in white patients (29% vs 11% in blacks, p = 0.005). The subset of black patients (n = 13) on a disconnect system (Y-set) had a peritonitis rate similar to their white controls on the Y set (0.41 vs 0.74 episodes/year, p = 0.27). There were no episodes of S. epidermidis peritonitis in this subset of black patients. Black patients had fewer S. aureus exit-site infections than white patients (21% vs 41%, p = 0.005). Peritonitis was the leading cause of transfer to hemodialysis in the black patients but not in the white patients. CONCLUSION: The susceptibility to S. aureus and S. epidermidis infections differs in black and white patients on peritoneal dialysis for unclear reasons. Peritonitis rates in black patients can be reduced to that of white patients if a disconnect system is used. PMID- 8443277 TI - Relative risks can be risky. PMID- 8443278 TI - Poor response to oral ciprofloxacin in the treatment of peritonitis in patients on intermittent peritoneal dialysis. AB - OBJECTIVES: To assess the clinical value of oral ciprofloxacin in the treatment of peritonitis in an intermittent peritoneal dialysis (IPD) population. DESIGN: Open nonrandomized prospective study. SETTING: Nephrology Peritoneal Dialysis Unit in a tertiary care, teaching hospital of the University of Toronto. PATIENTS: Subjects were participants of the IPD program with an acute episode of peritonitis defined as at least two of the following: 1. signs and symptoms of peritonitis, 2. cloudy peritoneal fluid with a white blood cell count of > 100/microL, 3. demonstration of bacteria in peritoneal effluent by gram stain or culture. Ten patients were enrolled in the study, but two were withdrawn because of side effects and growth of a resistant bacteria. INTERVENTIONS: Ciprofloxacin 750 mg po q12h for 2 doses, then 750 mg daily or 500 mg twice daily for 10 days. MAIN OUTCOME MEASURES: Efficacy was determined by clinical and microbiological assessment. Cure was defined as resolution of signs and symptoms with eradication of the causative organism. Peritoneal effluent and blood samples were analyzed for ciprofloxacin concentration. RESULTS: Ciprofloxacin was effective in treating only one of ten episodes of peritonitis. Seven patients were defined as microbiological failures (persistence or relapse of organisms). The signs and symptoms of peritonitis improved in 2 patients, but the remaining 5 failed clinically. Only Gram-positive organisms were cultured. CONCLUSIONS: Ciprofloxacin cannot be recommended for the treatment of intermittent peritoneal dialysis-related Gram-positive bacterial peritonitis. PMID- 8443279 TI - Endothelin-1 in continuous ambulatory peritoneal dialysis and hemodialysis patients: a preliminary study. AB - OBJECTIVE: To determine the effects of continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) on endothelin-1 (ET-1) levels in patients with end stage renal disease (ESRD) and to assess the relationship between plasma ET-1 levels and selected patient parameters. DESIGN: Prospective, nonrandomized comparison study. SETTING: Outpatient CAPD and HD units of a university medical center. PARTICIPANTS: Twelve ESRD patients (6 on CAPD and 6 on HD) and 5 healthy normotensive subjects. INTERVENTIONS: CAPD patients had blood and peritoneal dialysate samples collected and measurements made following an overnight exchange. HD patients had blood collected and measurements made at 0 hours (basal) and again at 3 hours during a midweek HD session. Blood samples were also collected from normal subjects and served as ET-1 controls. MEASUREMENTS: ET-1 and patient parameters (creatinine, peritoneal dialysate volume, blood pressure, body weight, age, and treatment duration) were determined. Data are reported as the mean +/- one standard deviation. RESULTS: Plasma and dialysate ET-1 levels in the CAPD group were 19.5 +/- 4.2 pg/mL and 9.2 +/- 4.2 pg/mL, respectively. The control group plasma and unused dialysate contained no detectable ET-1 (< 3.0 pg/mL, the limit of detection). The peritoneal clearance of ET-1 was less than that of creatinine (2.29 +/- 0.69 mL/minute vs 4.22 +/- 0.66 mL/minute, p = 0.005). The basal (0 hour) plasma ET-1 level in the HD group (16.5 +/- 7.8 pg/mL) did not differ from that of the CAPD group, p = 0.423. Furthermore, no differences in patient parameters were detected between the CAPD and basal HD groups. Although the mean arterial pressure (MAP) decreased during HD, the plasma ET-1 level at 3 hours (13.5 +/- 5.4 pg/mL) remained unchanged from the basal level, p = 0.307. An analysis of pooled data from the CAPD and HD groups revealed no significant correlation between plasma ET-1 and MAP, body weight, creatinine, or treatment duration. There was, however, a positive correlation between plasma ET-1 and age (r = 0.643, p = 0.024). PMID- 8443280 TI - Single-dose intraperitoneal vancomycin and oral ciprofloxacin for the treatment of peritonitis in CAPD patients: preliminary report. PMID- 8443281 TI - Unusual causes of peritonitis in three children receiving peritoneal dialysis. PMID- 8443282 TI - Vasovagal syncope related to peritoneal dialysate infusion. PMID- 8443283 TI - Hemorrhagic luteal cyst with massive hemoperitoneum in a patient on CAPD. PMID- 8443284 TI - Are exit-site infection rates lower with disconnect systems? PMID- 8443285 TI - Does low-calcium dialysate improve the nutritional status of CAPD patients? PMID- 8443286 TI - CAPD in a patient with spinal cord transection--a minefield of disasters. PMID- 8443287 TI - A multicenter, selection-adjusted comparison of patient and technique survival on CAPD and hemodialysis: a clarification. PMID- 8443288 TI - Neisseria mucosa peritonitis in CAPD: another case of the "nonpathogenic" Neisseriae infection. PMID- 8443289 TI - Experience with peritoneal catheters in Iraq. PMID- 8443290 TI - Fallopian tube capture of chronic peritoneal dialysis catheters. PMID- 8443291 TI - Respiratory distress syndrome in copper deficiency: an experimental model developed in rats. AB - An experimental model has been developed to investigate the effect of copper deficiency on lung maturity in the newborn rat. Three groups of female Sprague Dawley rats were used: the copper-deficient group was fed with a copper-free diet; the control group received a copper-adequate diet, and the pair-fed group was fed with a limited copper diet. After gestation and delivery, 35% of the newborn copper-deficient group showed respiratory distress syndrome (RDS). The neonatal lungs were isolated and processed for ultrastructural and biochemical study: A greater thickness of the air-blood barrier was observed in the lungs of the copper-deficient group, however, no other differences were observed in the rest of the pulmonary structures. Quantitative differences in pulmonary surfactant were not found in the three groups. The thickness of the air-blood barrier might explain the RDS observed in the copper-deficient newborns. PMID- 8443292 TI - In vitro binding of [3H]bilirubin to neurons in rat brain sections. AB - Slide-mounted 12-microns cryostat sections of rat brain were incubated with [3H]bilirubin, washed, dried, and apposed to emulsion-coated coverslips for autoradiography. The binding appeared to be nonsaturable. Within the gray matter, binding was concentrated over neuronal cell bodies (particularly evident over hippocampal pyramidal and granular cells, and over cerebellar Purkinje cells), suggesting that the preferential neuronal toxicity of bilirubin may be related to neuronal binding. Regional differences in bilirubin binding were not demonstrated. PMID- 8443293 TI - Effect of acute maternal alcohol consumption on the fetal ductus arteriosus in the rat. AB - This study was conducted to determine whether acute alcohol consumption in near term pregnant rats results in constriction of the fetal ductus arteriosus (DA). Twenty milliliters per kilogram of 30% (v/v) alcohol was administered via a stomach tube 0.5, 2, 4, 6 and 12 h prior to cesarean section and fetal sacrifice, at 1.00 p.m. on the 20th gestational day (day 20.5), in experimental groups A1 A5, respectively. Controls were given water alone. The calibers of the DA and pulmonary artery (PA) were measured using the whole-body freezing method with direct exposure of the DA and PA by shaving the frozen chests of the fetuses. The DA was significantly constricted 30 min after alcohol treatment. The constriction was also observed in groups A2-A4, but not in group A5. The PA was also less markedly but significantly constricted 30 min after alcohol administration, but groups A2-A5 showed normal PA caliber. It is concluded that alcohol has a constrictive effect on the DA when administered close to the end of gestation in the rat. PMID- 8443294 TI - Ornithine decarboxylase activity and urea in liver of late-pregnant rats. Effect of streptozotocin-induced diabetes. AB - It has been suggested that the induction of ornithine decarboxylase (ODC) activity during pregnancy might contribute to the low ureagenic flux that enables the pregnant mother to spare nitrogen and support growth. Thus, we have studied the ODC activity, and urea and polyamine levels in livers of virgin and 21-day pregnant rats, either in a basal state or after the induction of ureagenesis by inducing diabetes in rats by streptozotocin injection. Diabetes led to a marked increase in circulating and liver urea levels in virgin rats. This response was significantly reduced in late-pregnant animals. Diabetes did not modify ODC activity in pregnant rats, which showed much lower activities than their virgin controls. Diabetes caused a depletion of the liver spermine content in pregnant rats. Spermidine levels were higher in both groups of pregnant animals than in their respective controls. Our results suggest first that the mechanisms contributing to spare nitrogen in the pregnant mother are likely to be present in diabetic pregnant animals and, second, that ODC does not mediate the metabolic adaptations leading to a low ureagenic flux and a higher nitrogen retention at the last stage of pregnancy. PMID- 8443295 TI - Osteocalcin and human milk. PMID- 8443297 TI - Contemporary infectious exanthems. PMID- 8443296 TI - Urinary growth hormone excretion in preterm neonates. AB - We measured urinary growth hormone (U-GH), beta 2-microglobulin (U-B2) and serum growth hormone (S-GH) in preterm neonates on days 1, 4, 7, 14 and 28 of age. U-GH as well as U-B2 were high, particularly in the more premature and sick neonates with respiratory failure requiring mechanical ventilation. U-GH showed significant positive correlations with U-B2 throughout the study but with S-GH only on day 7. Therefore, we conclude that in preterm neonates, U-GH mainly reflects the degree of renal proximal tubular function, which is determined by the degree of renal maturation of the subject and of tubular injury due to disease states such as respiratory failure. PMID- 8443298 TI - Typhoid fever in Ethiopian immigrants to Israel and native-born Israelis: a comparative study. AB - Typhoid fever remains a major cause of mortality in developing countries, with a case-fatality rate (CFR) of 12%-32%, whereas in developed countries this rate has successfully been reduced to < 2%. The cause of this high CFR in developing countries was investigated by studying two populations of patients who had typhoid fever during the years 1984-1985: Ethiopian Jews who were infected in Africa (a region with a high CFR) and treated in Israel (a region with a low CFR) and native-born Israelis. The causative organisms were of similar phage types. Among 121 Ethiopian Jews there were two fatalities (CFR, 1.65%), and among 204 native-born Israelis there were three fatalities (CFR, 1.47%). Findings of the clinical course and treatment were similar for 15 Ethiopian Jews and 14 native born Israelis and consistent with those of reports from developed countries. We conclude that the high CFR for typhoid fever in Africa is due to delayed hospitalization and treatment rather than to differences in host factors or in the virulence of the pathogen and that mortality can be reduced by hastening hospitalization and treatment. PMID- 8443299 TI - Long-standing bacteremia caused by oral Actinobacillus actinomycetemcomitans in a patient with a pacemaker. AB - A case of symptomatic Actinobacillus actinomycetemcomitans bacteremia in a patient with an implanted pacemaker is presented. Attacks of fever occurred for at least 1 year. Oral examination revealed a mild form of periodontitis. A. actinomycetemcomitans was isolated from several oral sites. DNA fingerprinting of strains from the blood and the oral cavity showed identical profiles. This finding strongly suggests that the oral cavity was the primary source of A. actinomycetemcomitans bacteremia in this case. The patient was treated with the combination of metronidazole plus amoxicillin for 7 days, which resulted in a rapid cure and elimination of A. actinomycetemcomitans from the blood and the oral cavity. PMID- 8443300 TI - Ten-year experience with artificial pneumoperitoneum for end-stage, drug resistant pulmonary tuberculosis. AB - Artificial pneumoperitoneum is a form of collapse therapy that was used in the treatment of cavitary pulmonary tuberculosis before the availability of antimycobacterial chemotherapy. We report a series of cases of far-advanced pulmonary disease due to multiple-drug-resistant Mycobacterium tuberculosis, wherein artificial pneumoperitoneum with or without subsequent surgical extirpation was used as an adjunct to chemotherapy. Overall, among these desperate cases, therapeutic pneumoperitoneum provided no clear benefit. PMID- 8443301 TI - Splenic complications in malaria: case report and review. AB - Clinicians are increasingly confronted with diagnosis and management of malarial complications. In nonfalciparum malaria, severe complications usually involve the spleen, most notably among them the condition termed spontaneous splenic rupture. A case of infection due to Plasmodium malariae resulting in a symptomatic splenic hematoma is presented. Malarial splenic enlargement and pathology are reviewed, as well as splenic complications such as spontaneous rupture, hematoma, hyperreactive malarial syndrome, hypersplenism, ectopic spleen, torsion, and formation of cysts. Also evaluated are the 11 reported cases of spontaneous splenic rupture in malaria in the English-language literature from 1960 to 1991. Most cases of spontaneous splenic rupture in malaria occur during acute infection and are associated with Plasmodium vivax. Lack of prior immunity to malaria appears to be a major predisposing factor. Increasingly, splenic complications are managed by supportive care and spleen-conserving procedures to avoid postoperative and asplenic morbidity. PMID- 8443302 TI - Meningococcal disease in The Netherlands, 1958-1990: a steady increase in the incidence since 1982 partially caused by new serotypes and subtypes of Neisseria meningitidis. AB - In order to explain a threefold increase in the incidence of meningococcal disease in the Netherlands during the 1980s, we serotyped and subtyped Neisseria meningitidis isolates recovered between 1958 and 1990 from > 3,000 patients with systemic disease. No single strain could be held responsible for the increase. Apart from the newly introduced strain B:4:P1.4, which became the most prevalent phenotype in 1990 (21% of all isolates), the majority of the cases in 1990 were caused by many different strains that were already present in the Netherlands before 1980. For the period 1980-1990, a shift in the age distribution of patients with meningococcal disease from younger to older age categories was found, particularly with regard to cases due to meningococci of serogroup B; this shift is explained by the changing distribution of serotypes and subtypes within serogroup B. A polyvalent group B, class 1 outer-membrane-protein vaccine of a stable composition could theoretically have prevented approximately 80% of all group B meningococcal infections in the Netherlands during the past 30 years. PMID- 8443303 TI - The natural history of coccidioidal meningitis: VA-Armed Forces cooperative studies, 1955-1958. AB - From records on the clinical course of 699 military and veteran patients who had coccidioidomycosis before the advent of effective antifungal therapy, we identified 25 cases in which the manifestations of meningeal dissemination were described. Of 21 patients who had an identifiable initial infection, 16 developed meningeal symptoms (most frequently headache, vomiting, and nuchal rigidity) within the next 6 months. Associated pulmonary lesions were significantly more frequent in the right than in the left lung, as was also the case among 47 matched control patients who had coccidioidomycosis but not meningitis. Of 17 patients whose meningeal symptoms developed during the period studied, all died within 31 months. However, four of eight patients whose onset of symptoms preceded the study period survived for 55-146 months. Patients whose extrapulmonary dissemination involved only the meninges survived significantly longer than did those with more extensive infections. Even without therapy, the white blood cell count in cerebrospinal fluid markedly decreased during the course of the infection. The quantitative analysis provided herein offers a basis for meaningful comparisons with patients enrolled in current and future trials of therapy for coccidioidal meningitis. PMID- 8443304 TI - Serum adenosine deaminase 2 and neopterin levels are increased in a majority of hemophiliacs irrespective of infection with human immunodeficiency virus type 1. AB - We investigated serum levels of adenosine deaminase 2 (ADA2) and neopterin (NP) in hemophiliacs with or without infection with human immunodeficiency virus type 1 (HIV-1). The mean (+/- SD) serum ADA2 level in hemophiliacs positive for HIV-1 (45.2 +/- 17.6 U/L) and negative for HIV-1 (34.9 +/- 15.8 U/L) was significantly higher than that in healthy controls (12.0 +/- 7.0 U/L) (P < .01). The mean serum NP level was also higher in HIV-1-positive hemophiliacs (10.2 +/- 6.1 nmol/L) and HIV-1-negative hemophiliacs (7.0 +/- 2.9 nmol/L) than in the healthy controls (4.3 +/- 1.3 nmol/L). Although the HIV-1-positive hemophiliacs had higher mean ADA2 and NP levels than did hemophiliacs in the HIV-1-negative group (P < .01), the levels of most of the patients in both groups were similar. ADA2 and NP levels in serial samples from asymptomatic carriers and patients with stable AIDS showed no marked changes over a period of up to 6 years. These findings indicate that ADA2 and NP are not specific markers of HIV-1 infection in hemophiliacs. Nonspecific immunologic activation due to the repeated infusion of antihemophilic factor concentrate could be one cause for the increased serum levels of ADA2 and NP in hemophiliacs. PMID- 8443305 TI - Alternaria: a sinonasal pathogen of immunocompromised hosts. AB - Fungal infections remain a major cause of morbidity and mortality in immunocompromised patients. Although Candida and Aspergillus species are the most common fungal isolates, other less common fungal isolates such as Alternaria species are emerging as opportunistic pathogens associated with discrete clinical syndromes. We reviewed a 16-year consecutive series of bone marrow-transplant recipients and describe the presentation, treatment approach, and outcome of six cases of localized invasive sinonasal infection caused by Alternaria species in this series. At presentation, minimal or no symptoms were present, and nasal lesions of suspicious origin were often an incidental finding in evaluation of unexplained fever. Findings of sinus roentgenograms were normal for five of six patients. Infection occurred prior to white blood cell recovery in five of six cases. All infections were localized to the sinonasal region without evidence of dissemination. Treatment included systemic antifungal therapy and surgical debridement in all patients; granulocyte transfusions were performed for four patients. The infections resolved without sequelae in all but one patient who died of postoperative complications. Alternaria has a predilection for causing localized invasive sinonasal infection in immunocompromised hosts that can be successfully treated with an aggressive approach of combined modalities. PMID- 8443306 TI - Infective endocarditis due to nontoxigenic Corynebacterium diphtheriae: report of seven cases and review. AB - We report seven cases of endocarditis due to nontoxigenic Corynebacterium diphtheriae that occurred between October 1990 and September 1991. The patients all lived in the state of New South Wales, Australia. Three patients had preexisting cardiac abnormalities, and one patient used intravenous drugs regularly. The other three patients had no known risk factors for endocarditis. Notable clinical features were the aggressive nature of the infection, the occurrence of septic arthritis in four patients, and major vascular complications in four patients, one of whom died. One patient required urgent mitral valve replacement. All of the isolates were identified as non-toxigenic C. diphtheriae var gravis. Sporadic cases of endocarditis due to C. diphtheriae have rarely been reported; septic arthritis complicating endocarditis due to this organism has not previously been described. This report highlights the importance of identifying Corynebacterium isolates from normally sterile sites at the species level. PMID- 8443307 TI - Pertussis in Missouri: evaluation of nasopharyngeal culture, direct fluorescent antibody testing, and clinical case definitions in the diagnosis of pertussis. AB - No diagnostic test for pertussis in routine use in the United States has both high sensitivity and high specificity. During a statewide increase in the incidence of pertussis in Missouri, we studied the clinical features of 153 patients with suspected pertussis in the Greater St. Louis area from whom a specimen for pertussis culture had been taken between 15 May and 19 September 1989. In this cross-sectional study, nasopharyngeal cultures were more likely to be positive for persons whose specimens were collected < 21 days after cough onset (adjusted rate ratio [RRa] and 95% confidence interval = 3.4; 1.5-8.0) and who were not receiving erythromycin/sulfamethoxazole prior to the culture [RRa = 5.8; 0.8-40.6], who had received fewer than three prior doses of pertussis vaccine [RRa = 1.8; 0.8-4.2], and whose specimen was in transit to the laboratory for < 4 days [RRa = 2.0; 0.8-5.5]. Among children < 5 years of age, spasmodic cough plus a lymphocytosis of > 10,000/mm3 was the acute symptom complex associated with the highest predictive value for a positive culture result (67%). Cough for > or = 14 days plus whoop was sensitive (81%) and specific (58%) for identifying children with culture-confirmed pertussis. Direct fluorescent antibody staining performed well as a screening test for pertussis but requires substantial commitment of personnel and resources. In the absence of a positive culture result, clinical case definitions should be used for decision making (e.g., initiation of antimicrobial therapy and routine case reporting). PMID- 8443308 TI - Inhibition of the scarlet fever exanthem in concurrent varicella and group A streptococcus infection. AB - An atypical scarlet fever exanthem was noted in a 5-year-old child with varicella complicated by secondary group A beta-hemolytic streptococcus pneumonia and empyema. The rash consisted of symmetrical, concentric, circular exanthem-free zones surrounding individual varicella vesicles. The possible role of virus induced interferon in locally modifying the effect of streptococcal pyrogenic exotoxin is explored. PMID- 8443309 TI - Menstrual toxic shock syndrome complicated by persistent bacteremia: case report and review. AB - An unusual case of menstrual toxic shock syndrome (TSS) is described in which the patient had persistent Staphylococcus aureus bacteremia despite therapy with iv cloxacillin. There was no demonstrable evidence of endocarditis or an abscess as a focus for persisting bacteremia. The strain of S. aureus isolated from the blood and vagina produced toxic shock syndrome toxin 1 (TSST-1) and enterotoxin A. Bacteremia occurs uncommonly in association with TSS; however, aggressive high dose antistaphylococcal therapy should be instituted for treating this possible complication. PMID- 8443310 TI - Neurocysticercosis in a child with no history of travel outside the continental United States. AB - We present a case of neurocysticercosis in a 16-month-old girl who had no history of travel outside the continental United States. Immunoblot assays of serum and CSF were both reactive. The patient's father was found to be shedding Taenia ova in his stools, a finding that suggested direct fecal-oral transmission between himself and the patient. Given the possibility of this mode of transmission, the diagnosis of CNS cysticercosis should be considered for patients with compatible clinical presentations even if they do not have obvious risk factors such as travel to an area endemic for the parasite. PMID- 8443311 TI - A case of Ureaplasma urealyticum septic arthritis in a patient with hypogammaglobulinemia. AB - Patients with hypogammaglobulinemia have an increased susceptibility to certain infections. We describe the case of a patient with common variable hypogammaglobulinemia for whom the diagnosis of destructive monoarticular arthritis caused by Ureaplasma urealyticum was established after two nondiagnostic open biopsies had been performed. Mycoplasmal infection may involve a joint in hypogammaglobulinemic patients without causing macroscopic purulence in the joint. Histological examination of the bone may be helpful in the differentiation of an infectious process from the rheumatoidlike arthritis that occurs in such patients. Culture of involved bone in addition to synovium or synovial fluid may also be helpful in establishing the diagnosis. PMID- 8443312 TI - Nutritional status of children with dengue hemorrhagic fever. AB - Nutritional status was assessed for 100 patients with serologically confirmed dengue hemorrhagic fever (DHF), 125 patients with other infectious diseases who were admitted to Children's Hospital (Bangkok), and 184 healthy children. The assessment was done with use of the following parameters: weight for age, height for age, and circumference of the middle of the left arm. There were 13 patients classified as undernourished by weight for age, nine of whom were determined to have first-degree malnutrition; six of these had grade II severity of DHF and three had grade III DHF severity. Four patients, two each of grade II and III DHF severity, had second-degree malnutrition. All were considered to be healthy when nutritional status was assessed by height for age and mid-left arm circumference. The prevalence of 13% malnutrition found among patients with DHF is significantly lower than the prevalence of malnutrition found among patients with other infectious diseases and among healthy children. The study confirmed the observation generally made that most patients with DHF are not undernourished. PMID- 8443313 TI - Use of paromomycin for treatment of cryptosporidiosis in patients with AIDS. AB - Cryptosporidiosis in patients with AIDS often leads to a severe wasting illness that is difficult to treat. Recent reports suggest that paromomycin may be useful in the treatment of intestinal cryptosporidiosis. We reviewed our experience using paromomycin for the treatment of cryptosporidiosis in seven patients with AIDS. All patients received paromomycin (500 mg orally every 6 hours) for an average of 11.7 days. The mean follow-up period was 3.2 months. All patients had an initial response to paromomycin that was characterized by a decrease in frequency of diarrheal episodes, stabilization of body weight, and/or eradication of cryptosporidia from the stool. The mean number of diarrheal episodes decreased from 10.9 to 1.7 daily. Stabilization or increase in body weight was noted for five of seven patients, and eradication of oocysts was documented for three patients. Relapses or recurrences were noted for three patients. Treatment with paromomycin was well tolerated by all patients with the exception of two, who experienced nausea and abdominal discomfort. Thus, paromomycin appears to be a promising agent for treatment of acute cryptosporidiosis. PMID- 8443314 TI - Oral candidiasis is associated with low levels of parotid calprotectin in individuals with infection due to human immunodeficiency virus. AB - The level of the antifungal leukocyte protein calprotectin was determined in parotid saliva from 44 individuals with infection due to human immunodeficiency virus (HIV) and 19 healthy HIV-seronegative controls. Nine of the HIV-infected subjects suffered from oral candidiasis. Similar calprotectin levels were found in subjects with HIV infection as a whole group and in controls. When HIV infected individuals with or without oral candidiasis were compared, the calprotectin level was significantly lower in the former group (67 micrograms/L vs. 216 micrograms/L). We suggest that calprotectin may play a role in the defense against oral candidal infections in HIV-infected patients, although several other antimicrobial factors also are probably operative. PMID- 8443315 TI - Pyogenic liver abscess involving Actinomyces: case report and review. AB - We report a case of isolated hepatic actinomycosis and review 35 previously reported cases. Three-fourths of the reported patients were male, and more than one-half were between 30 and 50 years of age. Although some patients had oral disease or intraabdominal infections, the majority of cases were cryptogenic. Common presenting symptoms included fever, abdominal pain, and anorexia with weight loss. Findings on physical examination included pyrexia, abdominal tenderness, and hepatomegaly. Leukocytosis with a left shift, anemia, an elevated serum erythrocyte sedimentation rate, and an elevated level of alkaline phosphatase were almost universally present. Diagnosis was frequently made at the time of exploratory laparotomy, but percutaneous diagnostic procedures obviated the need for surgery in many recent cases. Microbiological diagnosis involved visualization of branching gram-positive Actinomyces organisms or recovery of organisms in anaerobic culture. Treatment most commonly consisted of prolonged administration of penicillin or tetracycline and was associated with an excellent outcome in the majority of cases. PMID- 8443316 TI - A serological survey and review of clinical Lyme borreliosis in Spain. AB - A serosurvey for Lyme disease was conducted by the National Reference Center for Microbiology in Spain. All serum specimens received from patients with erythema migrans (EM), arthritis, and cardiac and neurological disorders were tested for antibodies to Borrelia burgdorferi. Sera from 499 patients were tested. Of these patients, 310 had neurological disease, 101 had carditis, 79 had arthropathies, and 9 had EM; for 35 patients, a diagnosis of Lyme disease was confirmed. Of these 35, 68% had neurological disease, 6% had carditis, and 26% had EM. Twelve probable cases of Lyme disease were noted. The male-to-female ratio of patients with confirmed or probable disease was 1.6; all age groups were represented, but 25% of patients were within the age group of 0-9 years. The number of cases of Lyme disease decreases from the north of Spain (41%) to the south (26%), a distribution that is in agreement with the known range of Ixodes ricinus. Borrelia burgdorferi is a frequent cause of infection in some areas of Spain. It is possible that relapsing fever accounts for some of the serological reactivity to B. burgdorferi in residents of the south of Spain. PMID- 8443317 TI - History of malaria in the United States Naval Forces at war: World War I through the Vietnam conflict. AB - Malaria has had a major influence on military campaigns for thousands of years. In this paper we summarize the experience of U.S. Navy and Marine forces with malaria during wars of the twentieth century. During World War I, there were 4,746 new cases of malaria, 68,373 sick-days because of malaria, and 7 deaths due to malaria; during World War II, there were 113,256 new cases, 3,310,800 sick days, and 90 deaths; and during the Korean War, there were 4,542 new cases, 50,924 sick-days, and no deaths--since most infections were with Plasmodium vivax. During the Vietnam War, there were 24,606 cases of malaria, an estimated 391,965 sick-days because of malaria, and 46 deaths due to malaria. With the worldwide resurgence of malaria, the spread of drug-resistant strains of Plasmodium falciparum, the emergence of chloroquine-resistant P. vivax, and the increasing resistance of Anopheles mosquitoes to insecticides, malaria continues to be an enormous threat to U.S. Navy and Marine Corps personnel deployed to the tropics and subtropics. PMID- 8443318 TI - Treatment of infections due to enterococci with high-level gentamicin resistance and streptomycin susceptibility. PMID- 8443319 TI - Pancreatic tuberculosis as a manifestation of infection with the human immunodeficiency virus. PMID- 8443320 TI - Human anisakiasis misdiagnosed as abdominal angiostrongyliasis. PMID- 8443321 TI - Community-acquired meningitis due to penicillin-resistant Streptococcus pneumoniae. PMID- 8443322 TI - Diagnosis of perirectal Pneumocystis carinii infection by direct immunofluorescence. PMID- 8443323 TI - Oral ofloxacin: a critical review of the new drug application. PMID- 8443324 TI - Aureobasidium pullulans septicemia. PMID- 8443325 TI - Determination of the pathogenicity of Entamoeba histolytica. PMID- 8443326 TI - Inclusion of severely immunocompromised patients in studies assessing antibiotic efficacy. PMID- 8443327 TI - Exfoliative dermatitis during malarial prophylaxis with mefloquine. PMID- 8443328 TI - Endocarditis due to Staphylococcus capitis subspecies ureolyticus. PMID- 8443329 TI - Cryptosporidiosis in tourists returning from Egypt and the Island of Mauritius. PMID- 8443330 TI - The endemic infectious diseases of Somalia. PMID- 8443331 TI - Biophysical Journal 37th annual meeting. Washington D.C., February 14-18, 1993. Abstracts. PMID- 8443333 TI - Fluorescence studies of a local anesthetic-phospholipid interaction. AB - Steady-state and time-resolved fluorescence data are reported for the local anesthetic dibucaine in the absence and presence of phospholipid vesicles. These vesicles were comprised of dimyristylphosphatidyl choline and approximately 10% dimyristylphosphatidyl glycerol. Solute quenching studies show the bound drug to be protected from collision with iodide ion. The fluorescence lifetime of dibucaine is not significantly changed upon binding to vesicles. The fluorescence anisotropy of dibucaine increases upon association with the vesicles. Anisotropy decay measurements show that the rotational correlation time, phi, of bound dibucaine is increased about one hundred fold over that for free dibucaine. This indicates that the rotational motion of bound dibucaine is slowed by its interaction with the phospholipids. However, we find no evidence that the rotational motion of bound dibucaine is anisotropic. PMID- 8443332 TI - Local anesthetic-phospholipid interactions. Effects of ionic strength, temperature, and phospholipid mixtures on the binding of dibucaine to phospholipids. AB - The nature of the interaction of amphipathic drugs, such as dibucaine, with phospholipid bilayer membranes was investigated using equilibrium dialysis. Profiles for the binding of cationic dibucaine to unilamellar vesicles were obtained at different temperature and ionic strengths, and for mixtures of neutral phospholipid dimyristylphosphatidylcholine (DMPC) with negatively charged dimyristylphosphatidylglycerol (DMPG). The degree of binding of the cationic drug at pH 5 was found to be higher at temperatures above the Tm of DMPC (24 degrees C) than below Tm. Also enhanced drug binding was found to occur as the concentration of monovalent salt was increased (0.01-0.85 M) and as the percentage of DMPG was increased. Using the Stern and Guoy-Chapman model, which takes into consideration electrostatic effects, we were able to simultaneously fit all our binding data with a minimum of fitting parameters. These parameters (for data at 45 degrees C) are an association constant, K, of 330 M-1, a maximum possible number of drug molecules absorbed per unit surface of vesicle, sigma m+, of 1.70 x 10(-2) A2, and a surface area per bound drug, gamma D, of 48 A2. The data were fitted equally well by an alternate model in which binding of the drug is described as a partitioning equilibrium, with factors included for electrostatic effects and surface expansion caused by drug intercalation between the fatty acid chains. PMID- 8443334 TI - Effect of gamma-irradiation on the conformation of the native DNA molecule. AB - Extensive investigation of gamma-irradiated DNA solutions with the application of several informative physical methods suggested that at doses of 10-30 Gy the observed change in the size of the DNA molecule is due to a decrease in long range interactions in the macromolecule. The comparison of the results of investigations of non-irradiated and irradiated DNA and its complexes with low molecular weight ligands over a wide range of ionic strengths showed that these interactions are electrostatic in nature and are due to a decrease in the charge density on the DNA molecule when its solutions are irradiated. In the irradiation dose range discussed here, the persistent length of the DNA molecule determined by short-range interactions in the chain does not undergo pronounced changes. It is shown that the free ligand in the irradiated solution can protect the DNA molecule against radiation damage. In contrast, the ligand bonded by intercalation does not exhibit this ability. PMID- 8443335 TI - Tryptophan phosphorescence as a monitor of the solution structure of phosphoglycerate kinase from yeast. AB - The enzyme phosphoglycerate kinase from yeast possesses two tryptophan residues whose phosphorescence spectrum in low-temperature glasses is resolved into two distinct components with 0-0 vibronic bands centered at 408 and 412.5 nm. The thermal profile of the phosphorescence intensity and lifetime shows that the red (longer wavelength) component is quenched in fluid solutions so that the long lived phosphorescence observed at ambient temperature in buffer is due entirely to the blue (shorter wavelength) component. The remarkable heterogeneity in flexibility of the two chromophores' sites inferred from the thermal behaviour, when analyzed in terms of the crystallographic structure, allows to make a straightforward assignment of the long-lived emission to internal Trp-333. Because in buffer the phosphorescence is due to only one Trp residue the biphasic nature of the decay reveals the presence of stable, slowly interconverting, conformers with profound differences in the internal fluidity of the C-domain. Further, according to the triplet lifetime, complex formation with substrates affect the protein structure in a very selective way. Thus, while 3 phosphoglycerate has practically no influence on the average lifetime, Mg ATP and Mg ADP increases tau by a factor of 1.9 and 5.3, respectively. The change in lifetime implies a remarkable stiffening of the C-domain which is partly relaxed in ternary complexes with 3-phosphoglycerate. These findings are discussed in terms of ligand-induced "closed" conformations of the protein. PMID- 8443336 TI - The Donnan model derived from microstructure. AB - The ideal Donnan potential of an ionized polyelectrolyte medium is shown to be an approximate solution to a system of Poisson-Boltzmann (PB) equations for a periodic array of charged plates in an electrolyte bath. This result, derived using homogenization and scaling methods, demonstrates that the macrocontinuum, thermodynamic Donnan, and statistical mechanical PB models describe the same phenomenon: electrostatic repulsion between fixed-charged groups (albeit at different length scales). The Donnan approximation is accurate at low ionic strength (i.e., where the Debye length is much larger than the separation between charged plates), but is less faithful at physiologic and higher ionic strength. This work also provides a framework for relating theories of electrostatic repulsive interactions formulated at microscopic and macroscopic length scales. PMID- 8443337 TI - Effect of constraints by threonine on proline containing alpha-helix--a molecular dynamics approach. AB - Proline plays an important role in the secondary structure of proteins. In the pursuit of understanding its structural role, Proline containing helices with constraints have been studied by employing molecular dynamics (MD) technique. In the present study, the constraint introduced is a threonine residue, whose sidechain has intramolecular hydrogen bond interaction with the backbone oxygen atom. The three systems that have been chosen for characterization are: (1) Ace (Ala)12-Thr-Pro-(Ala)10-NHMe, (2) Ace-(Ala)13-Pro-Ala-Thr-(Ala)8-NHMe and (3) Ace (Ala)13-Pro-(Ala)3-Thr-(Ala)6-NHMe. The equilibrium structures and structural transitions have been identified by monitoring the backbone dihedral angles, bend related parameters and the hydrogen bond interactions. The MD averages and root mean square (r.m.s.) fluctuations are compared and discussed. Energy minimization has been carried out on selected MD simulated points in order to analyze the characteristics of different conformations. PMID- 8443338 TI - Biothermodynamic characterization of monocarboxylic and dicarboxylic aliphatic acids binding to human serum albumin: a flow microcalorimetric study. AB - Thermodynamic parameters have been evaluated for the binding of unbranched monocarboyxlic aliphatic acids (MCAs) of 4 to 16 carbons (MC4 to MC16) and dicarboxylic aliphatic acids (DCAs) of 4 to 16 carbons (DC4 to DC16) to human serum albumin (HSA) on the basis of microcalorimetric measurement at pH 7.4 and 37 degrees C by computer-fitting to single- and two-class binding models. Long chain MCAs (MC10 to MC16) and DCAs (DC14 and DC16) had the first class of binding sites with high affinity (large binding constant) of 10(5) to 10(6) M-1 and the second class with lower affinity and high capacity (large numbers of binding sites). Short- or medium-chain MCAs and DCAs bound to HSA at some low affinity binding sites. The binding constants of MCAs were ten times larger than those of DCAs. All the relationships between the thermodynamic parameters and alkyl-chain length of the acids showed clear-cut inflections in their plots around eight or nine methylene units. The free energy change of the first class of binding sites (- delta G1) became more negative with an increment of -1.0 kJ mol-1 CH2(-1) as the alkyl-chain length increased, but there were steep rises between MC9 and MC11 with -2.90 kJ mol-1 CH2(-1) and between DC9 and DC12 with -2.02 kJ mol-1 CH2(-1). The enthalpy change (- delta H) increased at the rate of -7.4 kJ mol-1 CH2(-1) to the maximum at MC9 and DC10, then decreased due to hydrophobicity of the alkyl chains. From compensation analyses (delta H vs. delta S and delta G), HSA binding sites were characterized into three groups. PMID- 8443339 TI - Activity of a chimeric promoter with the doubled CaMV 35S enhancer element in protoplast-derived cells and transgenic plants in maize. AB - A reproducible and efficient transformation system has been developed for maize that is based on direct DNA uptake into embryogenic protoplasts and regeneration of fertile plants from protoplast-derived transgenic callus tissues. Plasmid DNA, containing the beta-glucuronidase (GUS) gene, under the control of the doubled enhancer element (the -208 to -46 bp upstream fragment) from CaMV 35S promoter, linked to the truncated (up to -389 bp from ATG) promoter of wheat, alpha-amylase gene was introduced into protoplasts from suspension culture of HE/89 genotype. The constructed transformation vectors carried either the neomycin phosphotransferase (NPTII) or phosphinothricin acetyltransferase (PAT) gene as selective marker. The applied DNA uptake protocol has resulted at least in 10-20 resistant calli, or GUS-expressing colonies after treatment of 10(6) protoplasts. Vital GUS staining of microcalli has made possible the shoot regeneration from the GUS-stained tissues. 80-90% of kanamycin or PPT resistant calli showed GUS activity, and transgenic plants were regenerated from more than 140 clones. Both Southern hybridization and PCR analysis showed the presence of introduced foreign genes in the genomic DNA of the transformants. The chimeric promoter, composed of a tissue specific monocot promoter, and the viral enhancer element specified similar expression pattern in maize plants, as it was determined by the full CaMV 35S promoter in dicot and other monocot plants. The highest GUS specific activity was found in older leaves with progressively less activity in young leaves, stem and root. Histochemical localization of GUS revealed promoter function in leaf epidermis, mesophyll and vascular bundles, in the cortex and vascular cylinder of the root. In roots, the meristematic tip region and vascular tissues stained intensively. Selected transformants were grown up to maturity, and second generation seedlings with segregation for GUS activity were obtained after outcrossing. The GUS-expressing segregants carried also the NPTII gene as shown by Southern hybridization. PMID- 8443340 TI - Analysis of regulatory elements involved in stress-induced and organ-specific expression of tobacco acidic and basic beta-1,3-glucanase genes. AB - Infection of tobacco by tobacco mosaic virus (TMV) induces coordinate expression of genes encoding acidic and basic beta-1,3-glucanase isoforms. These genes are differentially expressed in response to other treatments. Salicylate treatment induces acidic glucanase mRNA to a higher level than basic glucanase mRNA. Ethylene treatment and wounding strongly induce the basic glucanase genes but have little effect on genes encoding the acidic isoforms. Furthermore, the basic glucanase genes are constitutively expressed in roots and lower leaves of healthy plants, whereas the acidic glucanase genes are not. In order to investigate how these expression patterns are established, we fused promoter regions of an acidic and a basic glucanase gene to the beta-glucuronidase (GUS) reporter gene and examined expression of these constructs in transgenic tobacco plants. A fragment of 1750 bp and two 5'-truncated fragments of 650 bp and 300 bp of the acidic glucanase promoter were tested for induction of GUS gene expression after salicylate treatment and TMV infection. Upstream sequences of 1750 bp and 650 bp were sufficient for induction of the reporter gene by salicylate treatment and TMV infection, but the activity of the 300 bp fragment was strongly reduced. The results suggest that the 1750 bp upstream sequence of the acidic glucanase gene contains multiple regulatory elements. For the basic glucanase promoter it is shown that 1476 bp of upstream sequences were able to drive expression in response to TMV infection and ethylene treatment, but no response was found to incision wounding. Furthermore, high GUS activity was found in lower leaves and roots of healthy transgenic plants, carrying the 1476 bp basic glucanase promoter/GUS construct. When the promoter was truncated up to position -446 all activity was lost, indicating that the region between -1476 and -446 of the basic glucanase promoter is necessary for organ-specific and developmentally regulated expression as well as for induced expression in response to infection and other stress treatments. PMID- 8443341 TI - Characterization of a Brassica napus myrosinase pseudogene: myrosinases are members of the BGA family of beta-glycosidases. AB - Myrosinase isoenzymes are known to be encoded by two different families of genes denoted MA and MB. Nucleotide sequence analysis of a Brassica napus genomic clone containing a gene for myrosinase revealed it to be a pseudogene of the MA family. The gene spans more than 5 kb and contains at least 12 exons. The exon sequence of the gene is highly similar to myrosinase cDNA sequences. However, the gene displays three potential or actual pseudogene characters. Southern blot analysis using probes from the 3' portions of the genomic and B. napus MA and MB cDNA clones showed that MA type myrosinases are encoded by approximately 4 genes, while MB type myrosinases are encoded by more than 10 genes in B. napus. Northern blots with mRNA from seeds and young leaves probed with the MA- and MB-specific probes showed that the MA and MB myrosinase gene families are differentially expressed. Myrosinases are highly similar to proteins of a beta-glycosidase enzyme family comprising both beta-glycosidases and phospho-beta-glycosidases of as diverged species as archaebacteria, bacteria, mammals and plants. By homology to these beta-glycosidases, putative active site residues in myrosinase are discussed on the basis of the similarity between beta-glycosidases and cellulases. PMID- 8443342 TI - Sorghum phosphoenolpyruvate carboxylase gene family: structure, function and molecular evolution. AB - Although housekeeping functions have been shown for the phosphoenolpyruvate carboxylase (EC 4.1.1.31, PEPC) in plants and in prokaryotes, PEPC is mainly known for its specific role in the primary photosynthetic CO2 fixation in C4 and CAM plants. We have shown that in Sorghum, a monocotyledonous C4 plant, the enzyme is encoded in the nucleus by a small multigene family. Here we report the entire nucleotide sequence (7.5 kb) of the third member (CP21) that completes the structure of the Sorghum PEPC gene family. Nucleotide composition, CpG islands and GC content of the three Sorghum PEPC genes are analysed with respect to their possible implications in the regulation of expression. A study of structure/function and phylogenetic relationships based on the compilation of all PEPC sequences known so far is presented. Data demonstrated that: (1) the different forms of plant PEPC have very similar primary structures, functional and regulatory properties, (2) neither apparent amino acid sequences nor phylogenetic relationships are specific for the C4 and CAM PEPCs and (3) expression of the different genes coding for the Sorghum PEPC isoenzymes is differently regulated (i.e. by light, nitrogen source) in a spatial and temporal manner. These results suggest that the main distinguishing feature between plant PEPCs is to be found at the level of genes expression rather than in their primary structure. PMID- 8443343 TI - Sigma-like transcription factors from mustard (Sinapis alba L.) etioplast are similar in size to, but functionally distinct from, their chloroplast counterparts. AB - Three proteins resembling bacterial sigma factors were previously isolated from mustard chloroplasts (K. Tiller, A. Eisermann and G. Link, Eur J Biochem 198: 93 99, 1991). These sigma-like factors (SLFs) confer DNA-binding and transcription specificity to a system consisting of Escherichia coli core RNA polymerase and cloned DNA regions that carry a chloroplast promoter. Sigma-like activity was now isolated also from etioplasts and could be assigned to three polypeptides of M(r) 67,000 (SLF67), 52,000 (SLF52) and 29,000 (SLF29), i.e. the same sizes as for the chloroplast SLFs. The purification scheme for the factors from either plastid type included an initial heparin-Sepharose and a final gel filtration step. For the etioplast factors, however, an additional phosphocellulose step was required to release these polypeptides from the RNA polymerase. The etioplast SLFs have similar, but not identical, salt requirements for DNA binding as compared to their chloroplast counterparts. Under conditions of maximum binding activity there is overall preference of etioplast SLFs for the psbA promoter over the trnQ and rps16 promoters. PMID- 8443344 TI - Characterization of a cDNA clone encoding a chloroplast-targeted Clp homologue. AB - Efforts to identify cDNA clones encoding chloroplastic envelope membrane proteins of Pisum sativum L. led to the isolation of a clone encoding a 92 kDa protein found in both the inner envelope membrane and the soluble fraction of chloroplasts. Sequential transcription and translation from the insert of this clone yielded a 102 kDa protein that could be imported into chloroplasts and processed to a 92 kDa form. Although the protein was identified because it reacted with antibodies to chloroplastic envelope proteins, the imported 92 kDa protein was recovered primarily in the soluble fraction of chloroplasts. The deduced amino acid sequence of this protein has strong similarity to the Clp proteins, a recently described family of highly conserved proteins present in all organisms examined to date. The physiological significance of the presence of this protein in chloroplasts is discussed. PMID- 8443345 TI - Jasmonic acid-inducible gene expression of a Kunitz-type proteinase inhibitor in potato tuber disks. AB - Messenger RNAs of a potato (Solanum tuberosum L.) Kunitz-type proteinase inhibitor(s) (PKPI) were present in potato disks excised from tubers stored for 14 months (old tubers) or 2 months (young tubers) after harvest, and disappeared during the aseptic culture. The PKPI mRNA accumulation was found to be induced in potato disks from the old tubers by the addition of jasmonic acid (JA) [3-oxo-2 (2'-cis-pentenyl)-cyclopentane-1-acetic acid]. PMID- 8443347 TI - Occurrence of the chromoplast protein ChrA correlates with a fruit-color gene in Capsicum annuum. AB - Plant geneticists have determined that the color of ripe fruits of sweet peppers (Capsicum annuum L.) is determined by four genes: y, c1, c2 and cl. We have compared the electrophoretic behavior of chromoplast membrane proteins of seven varieties of C. annuum which differ in these genes. ChrA was detected only in the varieties that had a y+ genotype, and was not affected by variations in the other three genes. The identity of ChrA was verified by probing blots of SDS gels with antiserum to ChrA. The second known chromoplast-specific protein, ChrB, was found to be independent of all four genes. No proteins correlating with c1, c2 or cl were detected in either one- or two-dimensional gels. PMID- 8443346 TI - Nucleotide sequence of maize chloroplast rpl32: completing the apparent set of plastid ribosomal protein genes and their tentative operon organization. AB - By sequencing the rpl32 gene, we have characterized the apparent complete set of the RP genes in Zea mays plastid genome. Key data for these 21 genes (total of 26 gene copies) and the proteins encoded by them are presented, and the operon organization is discussed on the basis of available transcription data. A nomenclature for the inferred 13 operons is suggested. PMID- 8443348 TI - Ferritin (mRNA, protein) and iron concentrations during soybean nodule development. AB - To study how iron-rich nodules concentrate and store iron, ferritin (mRNA, protein) was analyzed in developing soybean nodules and compared to nitrogenase (mRNA/activity) and leghemoglobin (mRNA, protein, heme). Both ferritin mRNA and protein concentrations increased early in nodulation. Later in nodulation ferritin protein declined, in contrast to the mRNA, as nitrogenase (mRNA and activity) increased and leghemoglobin (mRNA and protein) accumulated. A precursor/product relationship between iron stored in ferritin and iron in nitrogenase or leghemoglobin is suggested. The uncoordinated changes in ferritin mRNA and protein during nodulation contrast with nitrogenase mRNA and nitrogenase activity suggesting possible translational and posttranscriptional effects on ferritin expression. PMID- 8443349 TI - Expression of a phosphoenolpyruvate carboxylase promoter from Mesembryanthemum crystallinum is not salt-inducible in mature transgenic tobacco. AB - The 5' flanking region of a salt-stress-inducible, CAM-specific phosphoenolpyruvate carboxylase (PEPC) gene from the facultative halophyte Mesembryanthemum crystallinum, was fused to the beta-glucuronidase (GUS) reporter gene and introduced into Nicotiana tabacum SR1. The Ppc1 promoter displayed high levels of expression in transgenic tobacco quantitatively and qualitatively similar to a full-length 35S CaMV-GUS construct. Histochemical assays revealed that the full-length Ppc1-GUS fusions expressed GUS activity in all tissues except in root tips. While tobacco is capable of utilizing the Ppc1 cis-acting regulatory regions from M. crystallinum to yield high levels of constitutive expression, this glycophyte fails to direct a stress-inducible pattern of gene expression typical of this promoter in its native, facultative halophytic host. PMID- 8443350 TI - A putative beta-glucanase pseudogene behind the potato GBSS gene. AB - We identified an open reading frame (ORF) which is located closely behind the gene encoding granule-bound starch synthase (GBSS) of potato (Solanum tuberosum L.). The ORF ends with a perfect 43 bp direct repeat, which carries the stop triplet precisely at the beginning of the second repeat. The deduced protein shows homology with all known isoforms of plant beta-1,3-glucanases and beta-1,3 1,4-glucanases. Although the DNA sequence is unique in potato and tomato (Lycopersicon esculentum L.), no expression of the gene was found in these species. Taken together with the unusual codon usage and length of the predicted protein, this sequence could be a pseudogene. PMID- 8443351 TI - Subunit III (Psa-F) of photosystem I reaction center of the C4 dicotyledon Flaveria trinervia. AB - An immunological survey of C3, C4 and C3-C4-intermediate Flaveria species showed that subunit III (PsaF) of the photosystem I reaction center (PSI-RC) is present in all these species. This was confirmed by the isolation of the gene encoding the PSI-RC subunit III (PsaF) from Flaveria trinervia, the first psaF gene to be isolated from a C4 plant. The deduced amino acid sequence showed a high degree of similarity to the corresponding protein of spinach which is a C3 species. A region of 17 hydrophobic amino acids in the C-terminal part of the F. trinervia protein was found to be especially conserved in all PsaF proteins studied so far (cyanobacteria and Chlamydomonas). PMID- 8443352 TI - The expression of a rab-related gene, rab 18, is induced by abscisic acid during the cold acclimation process of Arabidopsis thaliana (L.) Heynh. PMID- 8443353 TI - [Dynamic inversion recovery snapshot FLASH MRT of focal nodular hyperplasia of the liver]. AB - 11 lesions of focal nodular hyperplasia (FNH) in 6 patients were studied by means of dynamic snapshot-FLASH MRI before and after bolus injection of Gd-DTPA. In addition, plain snapshot-FLASH images were compared with T1- and T2-weighted spin echo (SE) images and with T1-weighted breathhold-FLASH images. Highest FNH-liver signal-difference-to-noise ratios were obtained with snapshot-FLASH followed by T2-SE. In all patients contrast-enhanced serial snapshot-FLASH demonstrated reliably the typical haemodynamic appearance of FNH known from dynamic computed tomography. Because of its high intrinsic lesion-liver contrast and high time resolution dynamic snapshot-FLASH MRI may facilitate differential diagnosis of hepatic tumours. PMID- 8443354 TI - [Magnetic resonance tomography of chronic aortic dissection]. AB - 17 patients with chronic aortic dissection were examined by MRI. In 12 patients, comparison between gradient echo sequences and SE sequences was possible. Gradient echo sequences, unlike SE sequences, permitted evaluation of flow in the true and false lumen, reliable differentiation between thrombus and flowing blood and clear delineation of the intimal flap. An additional comparison between transoesophageal ultrasound and MRT in 15 patients showed significant advantages in favour of MRI. In three patients MRI was able to detect more proximal origins of the dissection. Moreover, MRI allowed evaluation of the major aortic branches and their relation to the dissection; this was not possible with ultrasound. MRI plays an important role in the follow-up of chronic aortic dissections. PMID- 8443355 TI - [PTA of 131 renal artery stenoses: management of hypertension and organ support]. AB - In this study 106 hypertensive patients (male n = 63, female n = 43) with angiographically proven renal artery stenosis (RAS) had PTA in 131 renal arteries (AS n = 86, FMD (fibromuscular dysplasia) n = 16, renal transplant n = 3, aortorenal bypass n = 1). Technical success rate was 86%, major complications were 3.5%, and minor complications were 12.8%. Following PTA (3-52 mo.) blood pressure was normalised in 25% (23/91), improved in 44% (40/91), and remained unchanged in 31% (28/91). Elevated serum creatinine levels (n = 26) (mean of 2.4 mg% before PTA) were regredient in 13 cases, remained stable in 6 cases, and were progredient in 7 cases. In short ostial RAS, technical and clinical results were not satisfactory. Long-term results were found to be better with FMD than with arteriosclerosis, with normal creatinine than with elevated levels, residual RAS after PTA of less than 50%, and with normal contralateral kidney function. PMID- 8443356 TI - [Computed tomography following extracorporeal shockwave lithotripsy of the kidneys. III. A prospective CT study of 105 patients and a 3-year follow-up of 23 patients using CT and 99mTc-MAG3 clearance]. AB - In 105 patients CT studies were done prospectively after renal ESWL with a second generation lithotripter. 33 (31%) of the patients had renal oedema (n = 8), renal (n = 20) or extrarenal (n = 31) bleeding. Three of the 23 patients who had a three year follow-up had chronic renal changes, 10 had renal stones. As blunt renal trauma can be the cause of renal hypertension a longterm follow-up is necessary in ESWL patients, particularly if there was renal bleeding after treatment. Further studies are needed to determine the exact risk of renal hypertension after ESWL. PMID- 8443357 TI - [Reduction of MRT time in the female pelvis using T2-weighted Fast-Spinecho(FSE) technique. A quantitative and qualitative comparison of conventional spinecho(SE) and Fast-Spinecho(FSE)-sequence]. AB - The fast spin echo (FSE) technique leads to time saving by individual phase coding of several spin echoes within one repetition interval. The new sequencing was compared quantitatively and qualitatively with conventional spin echo sequences in 30 patients with gynaecological pelvic disease. The signal-to-noise ratio was higher on FSE images in all tissues but to a variable degree. This led to an increased contrast-to-noise ratio, particularly between fat and solid structures, and to a reduction in the contrast between fat and fluid. Artifacts were reduced in FSE sequences leading to improved image quality in 83% and increased diagnostic information in 10%. This is of particular advantage when using time consuming T2-weighted sequences, which are necessary for the examination of the female pelvis. PMID- 8443358 TI - [X-ray studies of the peripheral joints: a comparison of digital luminescence radiography (DLR) and film-screen systems]. AB - 175 matched skeletal x-ray examinations were carried out by digital luminescent radiography (DLR) and conventional screen-film system combinations. In digital luminescent radiography (DLR) two differently postprocessed images were obtained from one x-ray exposure: A display with low spatial frequency enhancement was opposed to a second display with high edge enhancement. Conventional and digital images were evaluated randomly and separately by four radiologists using a questionnaire. DLR proved to be diagnostically equivalent to the conventional technique except for a diminished visibility of subtle erosions and fissures. As major advantages of DLR maybe pointed out that faulty exposures were avoided by the automatic adjustment of image brightness and that the soft tissue margins could be more easily delineated in displays with high edge enhancement than in conventional radiography. However, digital displays with high edge enhancement did not provide additional diagnostic information and led to artifacts at the edges of metal prostheses. PMID- 8443359 TI - [Rheumatoid arthritis of the wrist. Dynamic Gd-DTPA enhanced MRT]. AB - 21 patients with rheumatoid arthritis of the wrist diagnosed according to the criteria of the American Rheumatism Association were examined by dynamic MRT before and after the i.v. injection of Gd-DTPA (0.1 mmol/kg). The results were correlated with the clinical and radiological findings. The increased signal intensity of the pannus was 1.17 +/- 0.45%/sec and this differed significantly (p < 0.001) from bone marrow (0.16 +/- 0.11%/sec) and from muscle (0.25 +/- 0.16%/sec). Blood sedimentation rate correlated with the gradient of synovial proliferation (p < 0.05). There were no further statistically significant correlations between the clinical, radiological and MRT findings and the change in signal intensity from synovial proliferation as shown by dynamic MRT. PMID- 8443360 TI - [Chondromatous tumors in MRT: clinical picture in relation to localization and histopathology]. AB - 19 patients with histologically verified cartilaginous tumours (chondromas, chondrosarcomas) were examined with magnetic resonance imaging (MRI) in order to assess differences regarding the MR appearance of these tumours which would provide information on the biological behaviour of these lesions. MR findings were then correlated with histopathology. With regard to the signal behaviour of cartilaginous tumours a good correlation with histopathology could be established insofar as the relatively hypocellular tumours composed of hyaline cartilage exhibited a high signal level on T2-weighted images. There were no significant differences regarding signal characteristics of cartilaginous tumours in various anatomical locations. However, lesions located in the pelvis and the long bones showed predominantly peripheral enhancement whereas tumours of the skull base and larynx exhibited diffuse enhancement patterns in the majority of cases. 10 tumours (6 benign, 4 malignant) exhibited a lobular appearance. No relevant information in respect of tumour grading could be obtained. PMID- 8443361 TI - [MRT in cervical disk herniation: plain vs. contrast-enhanced images]. AB - Aim of this study was to assess the value of Gd-DTPA administration in MRI of cervical disk herniations. In 34 patients, showing 40 cervical disk herniations, plain proton density- and T1-weighted as well as contrast-enhanced T1-weighted 2D FLASH images were generated. Contrast between the herniated material and the CSF already was sufficient without administration of Gd-DTPA in all cases. Sufficient contrast between the herniations and the intraforaminal structures was obtained in 13/40 cases and 40/40 cases on plain and contrast-enhanced images, respectively. Definition of the herniated disks was judged to be sufficient in 30/40 cases on plain images and 40/40 cases on contrast-enhanced images. The diagnostic value of the images was improved in 3/12 lateral and 7/8 intraforaminal herniations by contrast administration, whereas there was no significant increase in diagnostic value in posterior or posterolateral herniations. As a result, Gd-DTPA administration is recommended if definition of lateral and intraforaminal disk herniations in MRI is poor. PMID- 8443362 TI - [Magnetic resonance tomography (MRT) in the diagnosis of Failed Back Surgery Syndrome (FBSS)]. AB - MRT was performed, using a 0.5 and 1.5 Tesla magnet, on 150 patients with FBSS between three days and 23 years following lumbar disc surgery. T1-weighted spin echo sequences were obtained before and after the application of gadolinium (0.15 mmol/kg). In 67 patients the MRT findings were compared with surgical observations. MRT had a sensitivity of 94% in diagnosing recurrent prolapse, a specificity of 100% and accuracy of 94%. The ventral epidural scar tissue, the disc and the neighbouring vertebral bodies showed increased contrast uptake over a prolonged post-operative period. PMID- 8443363 TI - [Chromolymphography in the localization of an abdominal lymphatic fistula]. PMID- 8443364 TI - Primary chyluria in an infant. PMID- 8443365 TI - Bilateral osteochondrosis of the distal epiphysis. A case report. PMID- 8443366 TI - [Traumatic pisiform luxation]. PMID- 8443367 TI - [Pseudohypertrophy of the olive following a traumatic brainstem lesion. MR tomographic follow-up study]. PMID- 8443368 TI - Renal colic associated with spontaneous urinary extravasation and pleural effusion. PMID- 8443369 TI - [Pleomorphic rhabdomyosarcoma of the heart with an unusual dissemination]. PMID- 8443370 TI - [Internal bile duct drainage using self-expanding metal stents in benign and malignant bile duct obstruction]. AB - Within a 4-year period, 24 patients were treated by internal biliary drainage using self-expanding wall stents. In 3 patients, a benign and in 21 patients a malignant obstruction were present. The stents were successfully placed in all cases with an incomplete tumour coverage in three cases. Complete relief of icteric symptoms was seen in 18 out of 24 cases. Acute complications requiring additional treatment occurred in 5 patients. Average survival time was 93 days for malignant disease and 26 months for benign lesions. Cumulative patency after 200 days was 63% for stents placed in malignant obstructions. Stents in benign obstructions remained open in all cases. PMID- 8443371 TI - [Modified implantation of a Wallstent in bile duct obstruction]. AB - The self-expanding Wallstents are increasingly applied in malignant biliary obstructions. The deployment of the stent from the covering membrane is a relatively complicated mechanism susceptible to trouble. Sometimes the deployment of the stent from the catheter fails and the incompletely deployed stent has to be removed and rejected. In a total of 9 patients with malignant bile duct obstruction 11 deployed stents were inserted in a technical modification over a 10 F sheath. The proposed technique has the advantages of a reduction of costs and of an exact placement of the stent. PMID- 8443372 TI - [Percutaneous drainage of abscesses, biliomas, seromas and hematomas following liver surgery. Experiences with 46 patients]. AB - Fifty-two fluid collections following hepatic surgery were diagnosed in 46 patients, mostly by sonography. These were treated percutaneously. In 7 patients ultrasound-guided puncture was used, in 36 patients catheter drainage was employed and in three drainage was instituted by a catheter in a pre-existing fistula. One patient with a bile leak in the hilar region had to undergo surgery. One patient died of multi organ failure following liver transplantation and another patient with advanced tumour died 78 days after the drainage procedure. The other patients recovered following conservative treatment (93.5%). PMID- 8443373 TI - Transfusion management of sickle cell disease. PMID- 8443374 TI - A serine/proline-rich protein is fused to HRX in t(4;11) acute leukemias. AB - Translocations involving chromosome band 11q23 in acute leukemias have recently been shown to involve the HRX gene that codes for a protein with significant similarity to Drosophila trithorax. HRX gene alterations are consistently observed in t(4;11) (q21;q23)-carrying leukemias and cell lines by Southern blot analyses and are accompanied by HRX transcripts of anomalous size on Northern blots. HRX-homologous cDNAs were isolated from a library prepared from t(4;11) carrying acute leukemia cells. cDNAs representative of transcription products from the derivative 11 chromosome were shown to contain HRX sequences fused to sequences derived from chromosome band 4q21. Fragments of the latter were used to clone and analyze cDNAs for wild-type 4q21 transcripts that predicted a 140-Kd basic protein (named FEL) that is rich in prolines, serines, and charged amino acids. FEL contains guanosine triphosphate-binding and nuclear localization consensus sequences and uses one of two possible 5' exons encoding the first 12 or 5 amino acids. After t(4;11) translocations, 913 C-terminal amino acids of FEL are fused in frame to the N-terminal portion of HRX containing its minor groove DNA binding motifs. These features are similar to predicted t(11;19) fusion proteins, suggesting that HRX consistently contributes a novel DNA-binding motif to at least two different chimeric proteins in acute leukemias. PMID- 8443375 TI - The place of high-dose BEAM therapy and autologous bone marrow transplantation in poor-risk Hodgkin's disease. A single-center eight-year study of 155 patients. AB - Although high-dose chemotherapy and autologous bone marrow transplantation (ABMT) are increasingly being used for the treatment of relapsed and resistant Hodgkin's disease, there have been few large, single-center studies reported with adequate follow-up to allow full evaluation of this therapeutic modality. We present 155 poor-risk Hodgkin's disease patients who received high-dose BEAM (BCNU, etoposide, cytosine arabinoside, and melphalan) chemotherapy and ABMT who have been studied over a period of 8 years. All patients had either not attained a remission on mechlorethamine, vincristine, procarbazine, prednisone-type therapy and had poor prognostic features at presentation, not attained a complete remission or relapsed within 1 year of an initial alternating regimen, or not attained remission with two or more lines of treatment. At the time of ABMT the relapse status of the patients was as follows: 46 patients were primarily refractory to induction therapy, 7 were good partial responders, 52 were in first relapse, 37 in second relapse, and 13 in third relapse. Seventy-eight patients had chemoresistant disease, 33 had chemosensitive disease at the time of ABMT, and 44 were untested for chemosensitivity at latest relapse. The procedure related mortality in the first 90 days post-ABMT of 10% overall. At 3 months 43 patients (28%) were assessed as complete responders, 72 patients had a partial response (46%), and 24 patients (16%) had no response or progression of disease. However, by 6 months, 53 (24%) patients were assessed as complete responders and 51 (33%) patients had nonprogressive disease. Forty-five patients had received radiotherapy post-ABMT to residual masses (41 patients) or to previous sites of bulk disease (4 patients). The actuarial overall and progression-free survival at 5 years was 55% and 50%, respectively. On multivariate analysis patients with bulk (masses > 10 cm), heavily pretreated patients (those receiving three or more lines of treatment) and females had a significantly poorer prognosis. Relapse status was also significant for progression-free survival in that patients in second (60%) and third relapse (70%) had a better prognosis than those in first relapse (44%) or with primary refractory disease (33%). Response to prior chemotherapy did not predict for progression-free survival. These results enable comparisons to be made between high-dose chemotherapy with ABMT and conventional dose salvage therapy. Furthermore, although the results as a whole are highly encouraging, certain groups carry an unfavorable prognosis. PMID- 8443376 TI - Treatment of myelodysplastic syndromes with all-trans retinoic acid. Leukemia Study Group of the Ministry of Health and Welfare. AB - We treated 23 patients with myelodysplastic syndromes (MDS); 2 refractory anemia (RA) with prior therapy, 11 RA with excess of blasts (RAEB), and 10 RAEB in transformation (RAEB-T), with daily oral 45 mg/m2 all-trans retinoic acid (ATRA) in a multiinstitutional prospective study. In two patients with RAEB and one with RAEB-T, a more than 1,000/microL increase of peripheral neutrophil counts was observed with some reduction of blast percentage in the bone marrow 2 to 9 weeks after the start of ATRA. However, the effect was transient and did not last for more than 5 weeks despite the continuation of ATRA therapy. In one other patient with RA, one patient with RAEB, and one patient with RAEB-T, slight increase of hemoglobin levels or reduction of blast percentage in bone marrow was noted. Toxicities attributable to ATRA were minimal and included cheilitis, xerosis, dermatitis, gastrointestinal disorders, abnormal liver function tests, and high serum triglyceridemia. Although ATRA works remarkably as a differentiation therapy in acute promyelocytic leukemia, its effect in MDS included in this study was modest. Further study of this agent alone or in combination may be warranted in less advanced stages of this disease. PMID- 8443377 TI - Monoclonal antibody J11d.2 recognizes cell cycle-dormant, primitive hematopoietic progenitors of mice. AB - It was reported that monoclonal antibody (MoAb) J11d.2 reacts with mature blood cells of mice but not with their progenitors. We tested in culture studies whether this antibody could be used for enrichment for primitive marrow progenitors. The majority of colony-forming cells including multipotential progenitors in the marrow cells from 5-fluorouracil (5-FU)-treated mice were J11d.2+, whereas most of the progenitors from normal mice were J11d.2-. In addition, formation of multilineage colonies from J11d.2+ in both 5-FU-treated and normal mice was augmented by interleukin 6. These observations indicated that MoAb J11d.2 recognizes cell cycle-dormant progenitors. We have recently described a simple method that provides 800-fold enrichment for the progenitors in post-5 FU marrow cells using MoAb D7 (anti-Ly-6A/E). When this method was modified to include sorting with MoAb J11d.2, D7+ J11d.2+ cells were 2,250-fold enriched for multipotential progenitors. Micromanipulation and culture of individual D7+ J11d.2+ cells showed that average plating efficiency of the cell population is approximately 70% and that about 30% of the progenitors are lymphohematopoietic in nature. These data demonstrate that J11d.2 is a useful MoAb for the isolation of primitive hematopoietic progenitors of mice. PMID- 8443378 TI - Mast cells and their committed precursors are not required for interleukin-3 induced histamine synthesis in murine bone marrow: characteristics of histamine producing cells. AB - In the present study we investigate the nature of the murine bone marrow cell subset responsible for the marked increase in histamine synthesis induced by interleukin-3 (IL-3). Because mast cells, and eventually their committed precursors, represent a potential source of histamine in this context, we examined their possible participation in this biologic activity with particular attention. We provide evidence that neither of these populations respond to IL-3 in terms of histamine synthesis and that other differentiated end cells or stromal components of the bone marrow are also not involved in this phenomenon. Starting from these findings, we further characterized the immature hematopoietic compartment responsible for IL-3-induced histamine synthesis using fluorescence activated cell sorter (FACS) sorting based on rhodamine retention or wheat germ agglutinin (WGA) affinity. These procedures have allowed us to ascribe the following features to histamine-producing cells: (1) They belong to a low density, progenitor-enriched bone marrow subset containing cells of relatively important size and internal structure. (2) The highest histamine levels are generated by the rhodamine-bright fraction of this population, while the most primitive rhodamine-dull cells do not express this biologic activity. (3) Histamine-producing cells do not copurify with colony-forming units in spleen day 7 and day 12 in WGA-bright fractions. (4) Their enrichment is associated with increased frequencies of cells forming colonies in methylcellulose (CFU-C), suggesting the involvement of several progenitors with partially limited differentiation potential in this biologic activity. PMID- 8443379 TI - Cooperative effects of interleukin-3 (IL-3), IL-5, and granulocyte-macrophage colony-stimulating factor: a new myeloid cell line inducible to eosinophils. AB - The cytokines interleukin-3 (IL-3); IL-5, and granulocyte-macrophage colony stimulating factor (GM-CSF) are known to contribute to the proliferation and differentiation of eosinophil progenitors. Recently, it was determined that the cellular receptors for these three cytokines share a common beta-chain while having unique alpha-chains. Thus, there is considerable interest in how these cytokines and their receptors interact in promoting production of eosinophils. We have established a cell line (AML14) from a patient with acute myelogenous leukemia that will consistently exhibit eosinophilic differentiation in suspension in response to IL-3, IL-5, and GM-CSF. Proliferation with only modest differentiative effects was observed in response to a single cytokine. Combinations of two cytokines gave variable results, with GM-CSF + IL-3 and IL-3 + IL-5 causing more proliferation than a single cytokine but little more differentiation. The combination of GM-CSF + IL-5 caused marked enhancement of eosinophilic differentiation with only modest augmentation of proliferation. The combination of all three cytokines was most effective in stimulating both proliferation and eosinophilic differentiation (up to 70% of cells) of AML14 cells. Specific binding of GM-CSF and IL-5 to AML14 cells can be conveniently studied by flow cytometric methods, and cross-competition of these two cytokines for their respective receptors was demonstrated. IL-3 was shown to partially compete for IL-5 binding on AML14 cells. Although specific IL-3 binding could not be demonstrated by flow cytometry, mRNA for the alpha-chains of the IL-3, IL-5, and GM-CSF receptors and the beta-chain common to all three receptors was detected in AML14 cells. The AML14 cell line may be a useful model for the study of cooperative interactions of IL-3, IL-5, GM-CSF, and their respective receptors in the promotion of eosinophil progenitor growth and differentiation. PMID- 8443380 TI - Zinc protoporphyrin in anemia of chronic disorders. AB - Hematofluorometric determination of zinc protoporphyrin (ZPP) is a screening method for the assessment of iron deficiency (ID). Chronic disorders are frequently accompanied by anemias of unclear origin, most probably caused by an impairment of iron metabolism. We investigated the relevance of ZPP for the detection of derangements of iron metabolism in anemias of chronic disorders (ACD). In 19 patients with ACD caused by chronic inflammatory non-neoplastic diseases, ZPP was determined and correlated with ferritin, transferrin saturation, and hemoglobin (Hb). Marrow sideroblast counts and semiquantitative grading of the marrow hemosiderin were performed in all patients to exclude ID and to show the decreased iron bioavailability. In all ACD patients who exhibited the typical laboratory findings of disturbed iron metabolism, such as hypoferremia, decreased transferrin saturation, decreased bone marrow sideroblasts, and increased marrow hemosiderin, strongly elevated ZPP levels were found (131 +/- 23 mumol/mol heme). ZPP returned to normal after successful treatment of the underlying disease. This is shown in three patients with polymyalgia rheumatica. We conclude that the fluorometric determination of ZPP allows detection and quantification of derangements of iron metabolism associated with chronic inflammatory disorders. By recording the derangements quantitatively, ZPP allows monitoring of therapy of chronic inflammatory diseases. PMID- 8443381 TI - Dissecting the hematopoietic microenvironment. IX. Further characterization of murine bone marrow stromal cells. AB - We have previously shown the adherent nontransformed, nonimmortalized murine bone marrow stromal cell (BMSC) population to consist of phagocytic macrophage and endothelial-like cells and nonphagocytic fibroblasts. Both colonial and near confluent growth of each cell type was obtained following magnetic bead separation, subsequent passaging, and sustained culture with fetal bovine serum and cytokines. Monoclonal antibody staining of antigenic determinants was used to characterize the phenotype of the stromal cell population in primary platings of murine colony-forming unit fibroblast and long-term bone marrow cultures. The antibodies MECA-99, MECA-32, and MJ7-18, raised against murine vascular endothelial antigenic determinants, and von Willebrand's factor all stained selectively for the rounded endothelial-like cells. Endothelial-like cells as well as macrophages expressed the myeloid surface antigens F4/80, 7/4, and Mac-1 under our culture conditions. The cytoskeleton of the stromal fibroblasts in culture was shown to express smooth muscle-specific actin isoforms, as evidenced by positive staining of stress fibers for alpha smooth muscle-1, CGA-7 (alpha/gamma isoforms), and HHF-35 (recognizes all muscle-specific actins). Under culture conditions, stromal fibroblasts were also found to be positive for a polyclonal smooth muscle myosin. It was found that these fibroblasts stained for collagens type I, III, and IV in our cultures. Although collagen type IV is considered a by-product of endothelial cells, endothelial-like cells in our cultures did not stain for any of the collagen types. We propose a classification listing for murine BMSCs as macrophages, endothelial-like cells, and fibroblasts that display smooth muscle-like characteristics in culture. PMID- 8443382 TI - Downregulation of GATA-1 expression during phorbol myristate acetate-induced megakaryocytic differentiation of human erythroleukemia cells. AB - Phorbol myristate acetate (PMA) induces the expression of megakaryocyte and/or platelet proteins during terminal differentiation of human erythroleukemia (HEL) cells. However, it is not established whether megakaryocytic differentiation is accompanied by the downregulation of the major erythroid transcription factor GATA-1 and the concomitant loss of the erythrocytic phenotype. Studies of the molecular mechanism of PMA-induced differentiation in HEL cells showed that when HEL cells are treated with PMA, they dramatically decrease the expression of the erythroid-specific gene glycophorin A at the mRNA level but apparently not at the steady-state protein level. In addition, a gel mobility shift assay was used to demonstrate that GATA-1, a major erythroid transcription factor normally present at high levels in HEL cells is downregulated after treatment with PMA. In contrast, the DNA-binding activities of transcription factors AP-1 and SP-1 are upregulated by PMA treatment of HEL cells. Furthermore, Northern blot analysis shows that PMA also downregulates the steady-state level of GATA-1 mRNA in HEL cells. The coordinated negative regulation of glycophorin A mRNA and GATA-1 expression after PMA treatment suggests that downregulation of GATA-1 expression may be partially responsible for the loss of the erythroid phenotype during megakaryocytic differentiation. The reported data also suggest that GATA-1 activity may not be essential for obtaining megakaryocytic phenotype during terminal differentiation in HEL cells. PMID- 8443383 TI - Bone marrow clones representing an intermediate stage of development between hematopoietic stem cells and pro-T-lymphocyte or pro-B-lymphocyte progenitors. AB - We have established in culture several nontransformed bone marrow clones (called PR) that show phenotypic and genotypic characteristics that distinguish them from totipotent stem cells and lineage-restricted Pro-T lymphocytes, Pro-B lymphocytes, and myeloid cell progenitors. In vivo and/or in vitro the PR clones give rise to T lymphocytes, B lymphocytes, and some myeloid-lineage cells, but they appear not to be able to generate cells of the erythroid lineage, nor can they rescue mice from a lethal dose of irradiation. We conclude that the PR clones are precursor cells representing an intermediate stage of development between the totipotential stem cell and lineage-restricted progenitor cells. The results described here support a model of blood cell formation in which stem cell differentiation is a progressive process marked by the stepwise loss of self renewal and functional potential. In addition, they provide evidence that cytokines and specialized microenvironments can direct the fate of the developing multipotent progenitor cells. PMID- 8443385 TI - Autoantibodies against platelet glycoproteins in autoimmune thrombocytopenic purpura: their clinical significance and response to treatment. AB - Autoantibodies against platelet glycoproteins (GP) have been demonstrated in patients with autoimmune thrombocytopenic purpura (ATP). However, their clinical and pathogenetic significance as well as their response to immunosuppressive treatment is unknown. Using an immunobead assay capable of measuring autoantibodies against GPIIb-IIIa and GPIb-IX, we studied 58 adult patients with active ATP (platelet count < 150 x 10(9)/L) and 26 patients with ATP in remission (platelet count > 150 x 10(9)/L and without any therapy at time of investigation). Platelet-associated autoantibodies were detected in 39 of 53 patients with active ATP (73.6%) and in 2 of 26 patients in remission (7.7%). Circulating plasma autoantibodies were noted in 17 of 58 patients in the group with active disease (29.3%) and in none of the patients in remission. Twelve patients with active ATP and autoantibodies against GPIIb-IIIa were studied prospectively during treatment with corticosteroids. Of eight patients whose platelet count normalized during treatment, platelet-associated and plasma antibodies decreased significantly in two or became undetectable in six. In contrast, of four patients whose platelet counts were unchanged or increased moderately, we noted no significant change in antibodies. Moreover, autoantibodies reappeared in two responding patients at the time of relapse. The effect of high-dose intravenous immunoglobulin was studied in six active ATP patients with antiglycoprotein autoantibodies and refractoriness to prednisone. In one patient who developed a sustained remission after IvIgG, platelet associated and plasma antibodies to GPIIb-IIIa decreased and became undetectable. In contrast, two patients who had only a transient rise of the platelet count after IvIgG showed no significant change in autoantibody. In three unresponsive patients, autoantibodies were without change in two and decreased transiently in one patient. We conclude that in ATP the presence of autoantibodies to GPIIb-IIIa and GPIb-IX is related to the activity of the disease. Corticosteroids may inhibit autoantibody formation in some ATP patients, whereas during the early response to IvIgG, autoantibody production may not be affected. PMID- 8443384 TI - Functional human transcobalamin II isoproteins are secreted by insect cells using the baculovirus expression system. AB - Transcobalamin II (TCII) is a cobalamin (Cbl, vitamin B12)-binding protein in mammalian plasma that facilitates the cellular uptake of the vitamin. To obtain human TCII in sufficient quantity for analytical studies, the complementary DNA (cDNA) encoding TCII was inserted into the plasmid PVL 1393, and the baculovirus expressing TCII was obtained by homologous recombination in Spodoptera frugiperda (SF9) insect cells by cotransfection with the wildtype virus. Under optimized conditions, SF9 cells infected with the recombinant virus secreted 2 to 4 micrograms of TCII per milliliter of culture medium. TCII did not accumulate in the SF9 cells and seemed to be constitutively secreted as observed previously in cultured human endothelial cells. The purified recombinant TCII has the same molecular weight by SDS-PAGE as purified human TCII. The recombinant TCII cross reacts with an antiserum to native human TCII, binds Cbl and facilitates the uptake of Cbl in eukaryotic cells by binding to the receptor for TCII-Cbl on the plasma membrane of K562 cells. Amino acid sequence analysis of the purified recombinant TCII identified two polypeptides, one identical to the amino acid sequence deduced from the cDNA and a second lacking the first and second N terminal residues. These sequences are identical to two TCII polypeptides purified from Cohn fraction III of pooled human plasma. The two forms of recombinant TCII have the same isoelectric points as the two predominant isoprotein forms of TCII in human serum. Since the baculovirus construct contains a single cDNA that can encode only one amino acid sequence, the two isoproteins in recombinant TCII must be generated by a mechanism other than allele specific expression. A plausible mechanism for generating isoproteins of nonglycosylated peptides, such as TCII, may be by splicing of the leader peptide at alternative sites. PMID- 8443386 TI - Increased macrophage colony-stimulating factor levels in immune thrombocytopenic purpura. AB - Thrombocytopenia is a dose-limiting toxicity of macrophage colony-stimulating factor (M-CSF) in preclinical and initial phase I trials. Modulation of macrophage-mediated platelet destruction in immune thrombocytopenic purpura (ITP) may be affected by M-CSF activity. In this study, plasma levels of M-CSF were determined by a sensitive radioimmunoassay in 23 patients with ITP. These were compared with control levels measured in 24 healthy subjects. M-CSF levels were significantly higher in the ITP patients than in the control subjects (218 v 179, P < .02); however, there was a great deal of overlap. The highest M-CSF levels (median = 299 U/mL) were observed in three patients with Evan's syndrome. Patients with severe ITP (platelets < 25,000/microL) had intermediate M-CSF levels (median = 231 U/mL) and those with mild thrombocytopenia (> 25,000/microL) had normal levels (median = 173 U/mL). Sixteen patients were treated with corticosteroids: 10 responded and 6 did not. Median M-CSF levels were higher in those who failed to respond compared with responders (272 v 202, P < .05). These findings suggest M-CSF may influence macrophage-mediated platelet destruction in ITP. PMID- 8443387 TI - Beta 2-glycoprotein I is a requirement for anticardiolipin antibodies binding to activated platelets: differences with lupus anticoagulants. AB - Antiphospholipid (aPL) antibodies are of major interest not only because the lupus anticoagulant (LA) causes an inhibition of in vitro blood coagulation, but also because the presence of aPL antibodies confers a risk of thrombosis. The inhibition of in vitro phospholipid-dependent coagulation (LA) is thought to be caused by the binding of LA to procoagulant phospholipid surfaces, thus impeding the clotting process. Another class of aPL antibodies are those originally described to be directed against negatively charged phospholipids, in particular cardiolipin (ACA). ACA are usually directed against a complex antigen consisting of negatively charged phospholipid and a plasma protein, beta 2-glycoprotein I (beta 2-GPI). Further, there is antibody heterogeneity even within individual patients so that ACA and LA are separable using physicochemical techniques such as ion exchange chromatography and chromatofocusing. Using such techniques we have enriched Ig fractions for LA and ACA from two patient plasmas. The majority of Ig with LA activity had a pI of 7.2 to 7.3 whereas ACA had a pI of 5.0 to 5.2. Using these enriched fractions labeled with [125I]-iodine we have shown that LA binds to platelets in a specific and saturable manner. Binding is dependent on thrombin activation. [125I]-ACA behaves differently. Like LA, binding is specific and dependent on thrombin activation but in this case requires the presence of beta 2-GPI. ACA, in the presence of beta 2-GPI, competes for binding with LA suggesting the same or contiguous site. There is no cross-reactivity of these antibodies with GPIIb/IIIa and the most likely binding site is phospholipid. In neither case does LA nor ACA have an effect on thrombin-induced release of serotonin or beta-thromboglobulin nor do they affect platelet aggregation induced by a number of agonists. This antibody binding may play an etiological role in thrombocytopenia associated with aPL, but does not explain thrombosis on the basis of hyperaggregability or increased platelet release. PMID- 8443388 TI - Real-time analysis of shear-dependent thrombus formation and its blockade by inhibitors of von Willebrand factor binding to platelets. AB - Two likely mechanisms for the initiation of arterial platelet thrombus formation under conditions of elevated fluid shear stresses are: (1) excessive adhesion and aggregation of platelets from rapidly flowing blood onto the exposed sub endothelium of injured, atherosclerotic arteries; or (2) direct, fluid shear stress-induced aggregation of platelets in constricted arteries with intact endothelial cells. Mechanism (1) was simulated using a parallel plate flow chamber, fibrillar collagen type I-coated slides, and mepacrine-labeled (fluorescent) platelets in whole blood anticoagulated with citrate, hirudin, unfractionated porcine heparin, or low molecular weight heparin flowing for 1 to 2 minutes at wall shear rates of 100 to 3,000 seconds-1 (4 to 120 dynes/cm2). The precise sequence of interactions among von Willebrand factor (vWF), glycoprotein (GP)Ib, and GPIIb-IIIa during platelet adhesion and subsequent aggregation were resolved by direct real-time observation using a computerized epifluorescence video microscopy system. Adhesion at high shear rates was the result of the adsorption of large vWF multimers onto collagen and the binding of platelet GPIb to the insolubilized vWF. Aggregation occurred subsequently and required the binding of ligands, including vWF via its RGD binding domain, to GPIIb-IIIa. Mechanism (2) was modeled by producing shear stresses of 90 to 180 dynes/cm2 in a rotational cone and plate viscometer, which aggregates platelets from platelet rich-plasma (PRP) anti-coagulated with citrate, hirudin, or either type of heparin in reactions that require large vWF multimers, Ca2+, adenosine diphosphate, and both GPIb and GPIIb-IIIa. Both vWF-mediated shear-aggregation in PRP and platelet-collagen adhesion in flowing whole blood (anticoagulated with citrate and hirudin) are inhibited by two potentially useful anti-arterial thrombotic agents: polymeric aurin tricarboxylic acid (ATA; 28.5 to 114 micrograms/mL), which binds to vWF and inhibits its attachment of GPIb, and a recombinant vWF fragment (rvWF445-733; 30 to 200 micrograms/mL) that binds to platelet GPIb (in the absence of any modulator) and blocks attachment of vWF multimers. Unfractionated heparin, but not low molecular weight heparin, apparently binds to rvWF445-733 and counteracts the inhibitory effects of the vWF fragment in vitro on shear-aggregation and platelet-collagen adhesion. PMID- 8443389 TI - Type 1 plasminogen activator inhibitor synthesis of endothelial cells is downregulated by smooth muscle cells. AB - Plasminogen activator inhibitor type 1 (PAI-1), the physiologic inhibitor of both tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA), is a major biosynthetic product of endothelial cells in vitro; endothelial cells in vivo, in contrast, do not appear to produce significant amounts of PAI-1 as made evident by in situ-hybridization studies in normal mice. This suggests that the high rate of PAI-1 synthesis of endothelial cells in vitro might be a result of the culture conditions. When human umbilical vein endothelial cells (HUVEC) were grown on human amniotic membranes, resembling the natural growth support instead of coated plastic, their morphology was changed from the cobblestone-like appearance on plastic to an in vivo like flagstone pattern. However, this morphological change had no significant effect on the synthesis and secretion of PAI-1. When smooth muscle cell (SMC) conditioned media (CM) were added to HUVEC cultures, PAI-1 antigen secretion of HUVEC was reduced by 40% to 60% as measured by enzyme-linked immunosorbent assay (ELISA). Immunoprecipitation experiments using 36S-methionine metabolically labeled HUVEC and Northern blot analysis of HUVEC PAI-1 mRNA indicate that this reduction was attributable to decreased PAI-1 synthesis and reduced steady-state levels of both the 3.2 kb and 2.2 kb form of PAI-1 mRNA. This effect was dose-dependent and observed under serum-containing as well as serum-free conditions, in the absence or presence of endothelial cell growth supplement (ECGS, 0 to 100 micrograms/mL) and attributable to a nondialyzable factor. Our data suggest that the high level of PAI-1 biosynthesis of endothelial cells in vitro may be attributable to the lack of a soluble factor produced by SMC, which controls and suppresses PAI-1 biosynthesis of endothelial cells in vivo. PMID- 8443390 TI - Regulation of fibrinolysis by platelet-released plasminogen activator inhibitor 1: light scattering and ultrastructural examination of lysis of a model platelet fibrin thrombus. AB - We have investigated the role of plasminogen activator inhibitor 1 (PAI-1) in the regulation of fibrinolysis using a model thrombus composed of thrombin-stimulated platelets, fibrin(ogen), plasminogen, and recombinant tissue-type plasminogen activator. Laser light scattering kinetic measurements showed that clot lysis was significantly delayed both by thrombin-stimulated platelets and their cell-free releasate. This delay in lysis was almost fully reversed by the addition of a PAI 1-specific monoclonal antibody that blocks the ability of PAI-1 to inhibit plasminogen activators. Lysis half-times exhibited a linear dependence on the concentration of PAI-1 antigen present, as determined by enzyme-linked immunosorbent assay (ELISA). Sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by immunoblotting confirmed the presence of PAI-1 antigen in the platelet releasates. Scanning electron micrographs of the model thrombus components sampled late in lysis showed considerable unproteolyzed fibrin still attached to platelets. Immunogold cytochemistry detected large amounts of PAI-1 antigen in the partially lysed platelet-fibrin thrombi. This PAI 1 appeared to be bound to the fibrin network rather than to the platelet surface itself. We conclude that the residual clots observed late in lysis represent platelet-associated fibrin to which platelet-released PAI-1 has bound, rendering it less susceptible to degradation. PMID- 8443391 TI - Antithrombin III Nagasaki (Ser116-Pro): a heterozygous variant with defective heparin binding associated with thrombosis. AB - A novel variant of antithrombin III (AT III) that lacks affinity for heparin was found in a 33-year-old man who suffered from recurrent cerebral infarction. The propositus had a history of recurrent ischemic attacks from the age of 28. He was obese and had a smoking habit (30 to 40 cigarettes/day), low high-density lipoprotein cholesterol, and a mild glucose intolerance as the possible risk factors for thrombosis. No family history of thromboembolic episodes was observed. Coagulation studies found low heparin cofactor activity (55%) of AT III, with a normal immunoreactive level (109.7%) and progressive antithrombin activity (117%). Other factors capable of predisposing him to hereditary thrombophilia were within normal ranges. Analysis by crossed immunoelectrophoresis in the presence of heparin and affinity chromatography on heparin-Sepharose demonstrated that the propositus' AT III was composed of two populations, one having no affinity for heparin and the other binding heparin normally. Nucleotide sequencing of 7 exons of the propositus' AT III gene using polymerase chain reaction and subcloning disclosed a transition of thymine to cytosine in exon 3a (codon 116) of the AT III gene leading to a Ser116-Pro conversion. Allele-specific oligonucleotide hybridization procedures confirmed the presence of the mutation in the propositus' genomic DNA. Using the same technique, the mutation was also found in his father's genomic DNA, but not in that of his mother. These findings indicate that Ser116 is an important amino acid residue in heparin binding and that the propositus is heterozygous for the abnormality. Furthermore, the fact that the propositus suffered from recurrent cerebral infarction suggested that being heterozygous for a heparin-binding defect would lead to a predisposition to thrombosis when associated with various risk factors. The name AT III Nagasaki is proposed for this variant AT III containing a novel Ser116-Pro mutation. PMID- 8443392 TI - Human high molecular weight kininogen binds to human umbilical vein endothelial cells via its heavy and light chains. AB - High molecular weight kininogen (HK) is a multifunctional plasma glycoprotein that occupies a critical position in pathways that link inflammation and coagulation. Excision of the vasoactive peptide bradykinin by plasma kallikrein results in kinin-free HK that consists of a 65-Kd N-terminal heavy chain (HK-HC) linked to the C-terminal 45-Kd light chain (HK-LC) by a disulfide bridge. HK-HC is an inhibitor of SH-proteases and HK-LC contains the binding sites for coagulation cofactors prekallikrein and factor XI. HK has previously been shown to bind specifically to human umbilical vein endothelial cells (HUVEC) in a zinc(2+)-dependent manner by a single class of high-affinity binding sites. We have further characterized that interaction in order to determine the cell binding regions of HK. Competition binding experiments have indicated that either HK-LC or HK-HC was able to inhibit the binding of labeled HK with a 50% inhibitory concentration (IC50) of 77 nmol/L and 89 nmol/L, respectively. Cleaved two-chain HK (HKa) had an IC50 of 73 nmol/L, whereas uncleaved HK had an IC50 of 335 nmol/L. Direct binding experiments have indicated that HUVEC bind both purified [125I]HK-HC and [125I]HK-LC in a zinc(2+)-dependent manner and that HK LC did not displace bound HK-HC. The light chain of low molecular weight kininogen or prekallikrein-binding region of HK did not inhibit the binding of HK to HUVEC. Our results, therefore, indicate that (1) HK is capable of binding to endothelial cells via both heavy and light chain moieties, (2) HKa has a higher affinity to HUVEC, and (3) purified heavy and light chains are capable of directly binding to HUVEC. The data are consistent with the presence of a single high-affinity site for HK on endothelial cells within which are subsites that bind to heavy and light chains. PMID- 8443393 TI - Lack of CD24 antigen expression in B-lineage acute lymphoblastic leukemia is associated with intrinsic radiation resistance of primary clonogenic blasts. AB - The radiation sensitivity of primary clonogenic blasts from 27 children with immunologically classified CD2-CD5-CD7-CD19+slg- B-lineage acute lymphoblastic leukemia (ALL) was analyzed using leukemic progenitor cell (LPC) colony assays. Radiation survival curves of primary clonogenic blasts (ie, LPC) were constructed for each patient using computer programs for the single-hit multitarget as well as the linear quadratic models of cell survival. The D0 values ranged from 49 to 891 cGy (median, 239 cGy; mean +/- SE, 307 +/- 44 cGy) and the alpha values ranged from 0.000 to 2.047 Gy-1 (median, 0.156 Gy-1; mean +/- SE, 0.284 +/- 0.078 Gy-1). Patients were divided into groups according to sex, age, white blood cell count (WBC) at diagnosis, plating efficiency of primary bone marrow blasts, and immunophenotype. Patient sex, age, WBC at diagnosis, or in vitro plating efficiency was not associated with radiation resistance. Notably, freshly isolated primary clonogenic blasts from patients with a CD19+CD24-CD34+ composite immunophenotype (stage I B-cell precursor [BCP]) had 2.2-fold higher D0 values (P = .005) and 3.4-fold lower alpha values (P = .05) than those from patients with a CD19+CD24+CD34+ (stage II BCP) or CD19+CD24+CD34- (stage III BCP) immunophenotype. The relative values for CD24- primary clonogenic blasts signify greater intrinsic radiation resistance. Furthermore, the CD19+CD24-CD34+ immunophenotype had a larger radiation resistant fraction. Whereas only 60% of CD19+CD24+CD34+ and 33% of CD19+CD24+CD34- cases had clonogenic blasts with alpha < or = 0.2, 100% of CD19+CD24-CD34+ cases had clonogenic blasts with alpha < or = 0.2. Furthermore, clonogenic blasts from established CD19+CD24- B-lineage ALL cell lines were significantly more radiation resistant than CD19+CD24+ B-lineage ALL cell lines. Notably, radiation doses sufficient to induce apoptosis of CD24- B-lineage ALL cells were higher than those capable of inducing apoptosis in CD24+ B-lineage ALL cells. Thus, the lack of CD24 surface antigen expression in B lineage ALL is associated with intrinsic radiation resistance at the level of primary clonogenic blasts. PMID- 8443394 TI - Type II interleukin-1 receptor is not expressed in cultured endothelial cells and is not involved in endothelial cell activation. AB - Interleukin-1 (IL-1) profoundly affects a number of functions of endothelial cells (EC). It was previously shown that EC express the type I 80-Kd IL-1 receptor (IL-1 RI). In this study we define the expression and functional significance of the type II IL-1R (IL-1 RII) in EC. Human umbilical vein EC did not express appreciable levels of IL-1 RII mRNA as assessed by Northern analysis or reverse transcription and polymerase chain reaction. Exposure to various cytokines (including IL-4, which augments IL-1 RII in neutrophils) failed to induce IL-1 RII mRNA. The binding of radiolabeled IL-1 beta to EC was blocked by antitype I (M4) but not by antitype II (M22) monoclonal antibodies (MoAbs). MoAbs directed against the IL-1 RI (M1 and M4) inhibited the induction of IL-6 and adhesion molecules in EC by IL-1, whereas an anti-IL-1 RII (M22) was inactive. The human IL-1 receptor antagonist (IL-1ra) preferentially interacts with IL-1 RI versus IL-1 RII in the mouse. IL-1 ra inhibited the response of mouse endothelial cells to IL-1. We conclude that EC selectively express the IL-1 RI and that this is involved in the response of this cell type to IL-1. PMID- 8443395 TI - Establishment and characterization of a new granulocyte-macrophage colony stimulating factor-dependent and interleukin-3-dependent human acute myeloid leukemia cell line (GF-D8). AB - A novel factor-dependent human myeloid leukemia cell line (GF-D8) was established from the peripheral blood of an 82-year-old man suffering from acute myeloblastic leukemia (AML). By morphology, cytochemical staining, and analysis of surface antigens, GF-D8 cells are myeloblasts of immature progenitor origin. The consensus karyotype is 45, XY, -5, 7q-, inv(7) (q31.2q36), 8q+, +8q+, 11q+, 12p-, -15, -17, + marker. The long-term survival and proliferation of GF-D8 cells is dependent on the presence of either granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3). Weak colony growth was observed after exposure of GF-D8 cells to stem cell factor (SCF) but not after exposure to granulocyte-CSF (G-CSF), macrophage-CSF (M-CSF), IL-1 beta, IL-2, IL-5, or tumor necrosis factor-alpha (TNF-alpha). GM-CSF- and IL-3-induced proliferation is dose dependent, with significant growth observed at concentrations as low as 0.1 ng/mL, but the combination of both factors has no synergistic effect. A significant proliferation is induced by GM-CSF and IL-3 even in serum-deprived cultures, although with a slightly decreased efficiency. GF-D8 cells were shown to express specific messenger RNAs for the alpha chains of the GM-CSF and IL-3 receptors as well as for the beta chain, common to both receptors. Interestingly, despite the absence of biologic response to G-CSF, specific transcripts for the G CSF receptor gene were similarly identified by reverse polymerase chain reaction analysis. GF-D8 cells represent a useful tool for studying chromosome abnormalities of human AML as well as the regulation of myeloid proliferation and differentiation in vitro. PMID- 8443396 TI - A human beta-globin gene fused to the human beta-globin locus control region is expressed at high levels in erythroid cells of mice engrafted with retrovirus transduced hematopoietic stem cells. AB - Retroviral-mediated gene transfer of human beta-globin provides a model system for the development of somatic gene therapy for hemoglobinopathies. Previous work has shown that mice receiving a transplant of bone marrow cells infected with a retroviral vector containing the human beta-globin gene can express human beta globin specifically in erythroid cells; however, the level of expression of the transduced globin gene was low (1% to 2% per gene copy as compared with that of the endogenous mouse beta-globin gene). We report here the construction of a recombinant retrovirus vector encoding a human beta-globin gene fused to the 4 major regulatory elements of the human beta-globin locus control region (LCR). The LCR cassette increases the level of expression of the globin gene in murine erythroleukemia cells by 10-fold. To study the level of expression in vivo, mouse bone marrow cells were infected with virus-producing cells and the transduced cells were injected into lethally irradiated recipients. In the majority of provirus-containing mice (up to 75%), expression of human beta-globin in peripheral blood was detected at least 3 to 6 months after transplantation. Twelve animals representative of the level of expression of the transduced gene in blood (0.04% to 3.2% of the endogenous mouse beta-globin RNA) were selected for further analysis. A range of 0.4% to 12% of circulating erythrocytes stained positive for human beta-globin protein. Based on these values, the level of expression of the transduced gene per cell was estimated to be 10% to 39% of the endogenous mouse beta-globin gene. These data demonstrate that fusion of the LCR to the beta-globin gene in a retroviral vector increases the level of beta-globin expression in murine erythroleukemia cells and suggest that high-level expression can be obtained in erythroid cells in vivo after transduction into hematopoietic stem cells. PMID- 8443397 TI - Immune activation and anemia of chronic disorders. PMID- 8443398 TI - Flow cytometric detection of the redistribution of the glycoprotein Ib-IX complex on thrombin-stimulated platelets is dependent on the type of antibody conjugate used. PMID- 8443399 TI - Prognostic significance of flow cytometric DNA analysis and estrogen receptor content in breast carcinomas--a 10 year survival study. AB - The prospective prognostic significance of flow cytometry derived DNA-ploidy status, the level of the S-phase fraction (SPF), estrogen receptor (ER) content, and combinations of these factors, was evaluated with respect to overall survival (OS) in a series of 516 breast cancer patients who were without signs of residual or distant disease after primary completed treatment. The median duration of survival follow-up time was ten years (range, 95-148 months) for surviving patients. Of the single factors, ER was the only significant predictor among node negative patients; the ten-year OS rate was 71% in cases with ER-rich tumors vs. 62% for ER-poor tumors (p = 0.03). Where tumors were both non-diploid and ER poor, the ten-year OS rate was 58%, as compared to 75% for the remaining node negative patients (p = 0.003), who constituted a low-risk group whose survival was comparable with that in the age-matched normal population. Among patients with 1-3 positive nodes, the ten-year OS rate was 65% in patients whose tumors had an SPF < 7.3% vs. 50% if the SPF was > or = 7.3% (p = 0.01), and 58% in cases with ER-rich tumors vs. 45% where the tumors were ER-poor (p = 0.02). In a multivariate analysis, apart from age and menopausal status the combination of ploidy status and ER content was the significant (p = 0.002) predictor of OS in node-negative patients. Thus, combining ploidy and ER status, both of which are variables easily determined, enabled the selection of a subgroup of patients at high risk of relapse and reduced survival whose prognosis should be improved by effective adjuvant systemic treatment, whereas the remaining low risk N0 patients can not be expected to derive any survival benefit from adjuvant therapy since their predicted survival is already on a par with that of the general population. PMID- 8443401 TI - Second and third line hormonotherapy in advanced post-menopausal breast cancer: a multicenter randomized trial comparing medroxyprogesterone acetate with aminoglutethimide in patients who have become resistant to tamoxifen. AB - In order to evaluate the efficacy of two different sequences of second and third line hormonotherapy in advanced post-menopausal breast cancer, 257 women aged 36 91 years (mean age: 63.6 years) who had become resistant to tamoxifen (TAM), entered into a multicenter randomized trial comparing two different regimens: 1) Aminoglutethimide (Ag) 500 mg/day with hydrocortisone supplementation from 30 to 60 mg/day; and 2) oral medroxyprogesterone acetate (MPA) 500 mg twice a day. 250 patients were evaluated following second line hormone therapy and, after cross over, 128 following third line hormonotherapy. No significant difference was observed, during either second or third line therapies, for toxicity, survival, or response rate; however, in both second and third line therapies the median time to progression was significantly longer with Ag therapy. PMID- 8443400 TI - Growth inhibition of 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors by controlled-release low-dose medroxyprogesterone acetate. AB - Since our previous findings had indicated that the androgenic steroid medroxyprogesterone acetate (MPA) exerts potent inhibitory effects on 7,12 dimethylbenz(a)anthracene (DMBA)-induced tumor growth, we have studied the effect of low doses of MPA released from Depo-Provera and from 50:50 poly[DL-lactide-co glycolide] microspheres in the same DMBA-induced tumor model. The present data show that single subcutaneous injection of a 4-month controlled-release formulation of biodegradable 50:50 poly[DL-lactide-co-glycolide] microspheres containing 10 mg of MPA giving serum levels of 3.14 +/- 0.32 ng/ml (8.12 +/- 0.83 nM) MPA causes a maximal or near-maximal 60% inhibition of tumor growth measured 56 days later. Such data suggest that controlled-release formulations giving constant and low blood levels of MPA could be used for the treatment of breast cancer in women. Such a low concentration of MPA should avoid the side effects observed with the high doses of the compound. PMID- 8443402 TI - Evaluation of binding of cytotoxic analogs of luteinizing hormone-releasing hormone to human breast cancer and mouse MXT mammary tumor. AB - The binding characteristics of several cytotoxic analogs of luteinizing hormone releasing hormone (LH-RH) developed in our laboratory were examined in membranes from human breast cancer and estrogen independent MXT mammary cancer. Specific binding of [125I]D-Trp6-LH-RH and the cytotoxic LH-RH analog [125I]T-98 ([D Lys6]LH-RH coupled to glutaryl-2-(hydroxymethyl)anthraquinone) (HMAQG) was demonstrated in membrane preparations from human breast and MXT mammary tumor cells. Ligand binding of T-98 was specific, saturable, and dependent on temperature, time, and plasma membrane concentration. Analysis of the binding data showed that in human breast cancer, interaction of [125I]T-98 was consistent with the presence of two classes of LH-RH receptors, one class showing high affinity and low capacity, and the other class showing low affinity and high capacity binding. In membranes from MXT mammary cancer, T-98 bound to one class of saturable, specific, noncooperative binding sites with high affinity and low capacity. The rates of association and dissociation for [125I]T-98 were calculated to be 4.757 x 10(8) M-1 min-1 and 0.016 min-1 (t1/2 = 38.7) in membranes from MXT mammary cancer. In human breast cancer, association rate constants (K1a and K1b) were 2.3 x 10(6) M-1 min-1 for binding to high affinity and 1.8 x 10(4) M-1 min-1 for binding to low affinity binding sites. Dissociation rate constants were K-1a = 0.0801 min-1 (t1/2a = 63.4 min) and K-1b = 0.0467 min 1 (t1/2b = 23.5 min), respectively. [125I]T-98 was not displaced by either unlabeled somatostatin or epidermal growth factor, but was displaced completely by unlabeled T-98 or [D-Trp6]LH-RH. The analysis of displacement curves of [D Trp6]LH-RH by cytotoxic agonists and antagonists of LH-RH synthesized in our laboratory showed that T-121, AJ-11, T-120, T-133, and T-98 were the most potent in displacing [125I]D-Trp6-LH-RH from breast and MXT cancer membranes. Binding kinetics and analyses of displacement curves of [125I]D-Trp6-LH-RH and [125I]T-98 in membranes of human breast cancer and estrogen independent MXT mouse mammary cancer suggest that binding of the cytotoxic analog T-98 to the LH-RH receptor proceeds reversibly like that of its congeners without cytotoxic radicals. Our findings may provide a stimulus for further studies with LH-RH analogs carrying cytotoxic radicals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8443403 TI - Hereditary breast cancer in Sweden: a predominance of maternally inherited cases. AB - The family history of breast cancer was studied in 1975 breast cancer patients of all ages. All the patients were found in an ongoing care program for breast cancer patients in the Stockholm area. One hundred and thirty-three families (6.7%) with hereditary breast cancer, 87 (4.4%) families with hereditary breast- and other cancers, and 14 (0.7%) families with the SBLA syndrome were found. There was no association between familiarity and bilateral disease, but familial cases tended to be younger at the time of diagnosis. Determination of the parental origin of the disease gene among the index cases revealed twice as many cases where the disease was maternally transmitted. This might be due to a better prognosis when the predisposing gene is maternally transmitted, and could be explained by parental imprinting or environmental factors influencing the expression of the gene. PMID- 8443404 TI - Lipid-associated sialic acid levels in human breast cyst fluids. AB - Benign mammary gross cystic disease is the most common breast lesion. Women with apocrine changes of epithelium lining the cysts are at higher risk for developing breast cancer than the normal female population. Sialic acid has drawn considerable interest because of carbohydrate aberrations in malignant cells. The current investigation determined the concentrations of lipid-associated sialic acid (LASA) in 62 breast cyst fluids and sera. Data analyses show a significant increase in the mean values of LASA in metabolically active apocrine cysts when compared to the cysts with Na+/K+ > 3 (flattened cysts) (p < 0.001). The greater LASA levels in cyst fluids with lower intracystic Na+/K+ ratios could represent an altered expression of biosynthetic activity of the surrounding apocrine cell surface sialoglycolipid metabolism, providing a possible explanation of why women with apocrine cysts may be at greater cancer risk and being useful in further studies on functional stage changes in the cysts and their relationship to breast cancer. PMID- 8443405 TI - A double life: cytosolic aconitase as a regulatory RNA binding protein. PMID- 8443407 TI - Patterns of mitochondrial sorting in yeast zygotes. AB - Inheritance of mitochondrial DNA (mtDNA) in Saccharomyces cerevisiae is usually biparental. Pedigree studies of zygotic first buds indicate limited mixing of wild-type (p+) parental mtDNAs: end buds are frequently homoplasmic for one parental mtDNA, while heteroplasmic and recombinant progeny usually arise from medial buds. In crosses involving certain petites, however, mitochondrial inheritance can be uniparental. In this study we show that mitochondrial sorting can be influenced by the parental mtDNAs and have identified intermediates in the process. In crosses where mtDNA mixing is limited and one parent is prelabeled with the matrix enzyme citrate synthase 1 (CS1), the protein freely equilibrates throughout the zygote before the first bud has matured. Furthermore, if one parent is p0 (lacking mtDNA), mtDNA from the p+ parent can also equilibrate; intracellular movement of mtDNA is unhindered in this case. Surprisingly, in zygotes from a p0 CS1+ x p+ CS1- cross, CS1 is quantitatively translocated to the p+ end of the zygote before mtDNA movement; subsequently, both components equilibrate throughout the cell. This initial vectorial transfer does not require respiratory function in the p+ parent, although it does not occur if that parent is p-. Mouse dihydrofolate reductase (DHFR) present in the mitochondrial matrix can also be vectorially translocated, indicating that the process is general. Our data suggest that in zygotes mtDNA movement may be separately controlled from the movement of bulk matrix constituents. PMID- 8443406 TI - Functional homology of protein kinases required for sexual differentiation in Schizosaccharomyces pombe and Saccharomyces cerevisiae suggests a conserved signal transduction module in eukaryotic organisms. AB - We present genetic evidence that three presumptive protein kinases of Schizosaccharomyces pombe, byr2, byr1, and spk1 that are structurally related to protein kinases of Saccharomyces cerevisiae, STE11, STE7, and FUS3, respectively, are also functionally related. In some cases, introduction of the heterologous protein kinase into a mutant was sufficient for complementation. In other cases (as in a ste11- mutant of S. cerevisiae), expression of two S. pombe protein kinases (byr2 and byr1) was required to observe complementation, suggesting that byr2 and byr1 act cooperatively. Complementation in S. pombe mutants is observed as restoration of sporulation and conjugation and in S. cerevisiae as restoration of conjugation, pheromone-induced cell cycle arrest, and pheromone-induced transcription of the FUS1 gene. We also show that the S. pombe kinases bear a similar relationship to the mating pheromone receptor apparatus as do their S. cerevisiae counterparts. Our results indicate that pheromone-induced signal transduction employs a conserved set of kinases in these two evolutionarily distant yeasts despite an apparently significant difference in function of the heterotrimeric G proteins. We suggest that the STE11/byr2, STE7/byr1, and FUS3/spk1 kinases comprise a signal transduction module that may be conserved in higher eukaryotes. Consistent with this hypothesis, we show that a mammalian mitogen-activated protein (MAP) kinase, ERK2, can partially replace spk1 function in S. pombe. PMID- 8443408 TI - Disruption of epithelial cell-cell adhesion by exogenous expression of a mutated nonfunctional N-cadherin. AB - Cadherins, a family of transmembrane cell-cell adhesion receptors, require interactions with the cytoskeleton for normal function. To assess the mechanisms of these interactions, we studied the effect of exogenous expression of a mutant N-cadherin, cN390 delta; on epithelial cell-cell adhesion. The intracellular domain of cN390 delta was intact but its extracellular domain was largely deleted so that this molecule was not functional for cell adhesion. cDNA of cN390 delta was attached to the metallothionein promoter, and introduced into the keratinocyte line PAM212 expressing endogenous E- and P-cadherin. When the expression of cN390 delta was induced by Zn2+, cadherin-dependent adhesion of the transfected cells was inhibited, resulting in the dispersion of cell colonies, although their contacts were maintained under high cell density conditions. In these cultures, cN390 delta was expressed not only on the free surfaces of the cells but also at cell-cell junctions. The endogenous cadherins were concentrated at cell-cell junctions under normal conditions. As a result of cN390 delta expression, however, the endogenous cadherins localizing at the cell-cell junctions were largely diminished, suggesting that these molecules were replaced by the mutant molecules at these sites. As a control, we transfected the same cell line with cDNA of a truncated form of N-cadherin cadherin whose intracellular C terminus had been deleted leaving the extracellular domain intact. This molecule had no effect on cell-cell adhesion, nor did it localize to cell-cell contact sites. We also found that the association of the endogenous cadherins with alpha- and beta-catenins and plakoglobin was not affected by the expression of cN390 delta, which also formed a complex with these molecules, suggesting that no competition occurred between the endogenous and exogenous cadherins for these cytoplasmic proteins. These and other additional results suggest that the nonfunctional cadherins whose intracellular domain is intact occupy the sites where the endogenous cadherins should localize, through interactions with the cytoskeleton, and inhibit the cadherin adhesion system. PMID- 8443409 TI - Phosphorylation sites at the C-terminus of the platelet-derived growth factor receptor bind phospholipase C gamma 1. AB - We have identified two tyrosine phosphorylation sites, Tyr 1009 and Tyr 1021, in the C-terminal noncatalytic region of the human platelet-derived growth factor (PDGF) receptor beta subunit. Mutant receptors with phenylalanine substitutions at either or both of these tyrosines were expressed in dog epithelial cells. Mutation of Tyr 1021 markedly reduced the PDGF-stimulated binding of phospholipase C (PLC) gamma 1 but had no effect on binding of the GTPase activator protein of Ras or of phosphatidylinositol 3 kinase. Mutation of Tyr 1009 reduced binding of PLC gamma 1 less severely. Mutation of Tyr 1021, or both Tyr 1009 and Tyr 1021, also reduced the PDGF-dependent binding of a transiently expressed fusion protein containing the two Src-homology 2 domains from PLC gamma 1. Mutation of Tyr 1021, or both Tyr 1009 and Tyr 1021, greatly reduced PDGF stimulated tyrosine phosphorylation of PLC gamma 1 but did not prevent the tyrosine phosphorylation of other cell proteins, including mitogen-activated protein kinase. We conclude that Tyr 1021, and possibly Tyr 1009, is a binding site for PLC gamma 1. PMID- 8443410 TI - Regulation of albumin gene expression in hepatoma cells of fetal phenotype: dominant inhibition of HNF1 function and role of ubiquitous transcription factors. AB - Two widely used hepatoma cell lines, mouse BW1J and human HepG2, express gene products characteristic of fetal hepatocytes, including serum albumin, whereas reporter genes driven by the albumin promoter are expressed at very low levels compared with highly differentiated hepatoma cells. We have investigated the low albumin promoter activity in BW1J cells to understand differences in liver gene regulation between fetal and adult cells. Addition of the albumin upstream enhancer, or any other fragment of the albumin gene, failed to modify expression of the transfected promoter in BW1J cells. Analysis of cis elements of the albumin promoter showed that, in contrast to highly differentiated H4II cells, in BW1J cells the activity largely depends on ubiquitous transcription factors. Both BW1J and HepG2 cells produce the liver-enriched transcription factor HNF1; dimerization and DNA binding properties are identical to those of liver HNF1, yet the protein fails to show the anticipated transcriptional stimulatory activity. A transfected HNF1 expression vector strongly trans-activates the albumin promoter in HepG2 but only weakly in BW1J cells, and in hybrids (BW1J x Fao), inefficient HNF1 function is dominant. We conclude that hepatoma cells of the fetal phenotype are deficient in the use of HNF1 to drive transcription of the albumin gene and that they harbor a dominant modulator of HNF1 function. PMID- 8443411 TI - Phosphorylation independent activation of human cyclin-dependent kinase 2 by cyclin A in vitro. AB - p33cdk2 is a serine-threonine protein kinase that associates with cyclins A, D, and E and has been implicated in the control of the G1/S transition in mammalian cells. Recent evidence indicates that cyclin-dependent kinase 2 (Cdk2), like its homolog Cdc2, requires cyclin binding and phosphorylation (of threonine-160) for activation in vivo. However, the extent to which mechanistic details of the activation process are conserved between Cdc2 and Cdk2 is unknown. We have developed bacterial expression and purification systems for Cdk2 and cyclin A that allow mechanistic studies of the activation process to be performed in the absence of cell extracts. Recombinant Cdk2 is essentially inactive as a histone H1 kinase (< 4 x 10(-5) pmol phosphate transferred.min-1 x microgram-1 Cdk2). However, in the presence of equimolar cyclin A, the specific activity is approximately 16 pmol.mon-1 x microgram-1, 4 x 10(5)-fold higher than Cdk2 alone. Mutation of T160 in Cdk2 to either alanine or glutamic acid had little impact on the specific activity of the Cdk2/cyclin A complex: the activity of Cdk2T160E was indistinguishable from Cdk2, whereas that of Cdk2T160A was reduced by five-fold. To determine if the Cdk2/cyclin A complex could be activated further by phosphorylation of T160, complexes were treated with Cdc2 activating kinase (CAK), purified approximately 12,000-fold from Xenopus eggs. This treatment resulted in an 80-fold increase in specific activity. This specific activity is comparable with that of the Cdc2/cyclin B complex after complete activation by CAK (approximately 1600 pmol.mon-1 x microgram-1). Neither Cdk2T160A/cyclin A nor Cdk2T160E/cyclin A complexes were activated further by treatment with CAK. In striking contrast with cyclin A, cyclin B did not directly activate Cdk2. However, both Cdk2/cyclin A and Cdk2/cyclin B complexes display similar activity after activation by CAK. For the Cdk2/cyclin A complex, both cyclin binding and phosphorylation contribute significantly to activation, although the energetic contribution of cyclin A binding is greater than that of T160 phosphorylation by approximately 5 kcal/mol. The potential significance of direct activation of Cdk2 by cyclins with respect to regulation of cell cycle progression is discussed. PMID- 8443412 TI - TGN38/41 recycles between the cell surface and the TGN: brefeldin A affects its rate of return to the TGN. AB - TGN38 and TGN41 are isoforms of an integral membrane protein (TGN38/41) that is predominantly localized to the trans-Golgi network (TGN) of normal rat kidney cells. Polyclonal antisera to TGN38/41 have been used to monitor its appearance at, and removal from, the surface of control and Brefeldin A (BFA)-treated cells. Antibodies that recognize the lumenal domain of TGN38/41 are capable of specific binding to the surface of both control and BFA-treated cells. In both control and BFA-treated cells internalized TGN38/41 is targeted to the TGN; however, there are differences in 1) the morphology of the intracellular structures through which TGN38/41 passes and 2) the kinetics of internalization. These data demonstrate that TGN38/41 cycles between the plasma membrane and the TGN in control and BFA-treated cells and suggest that recycling pathways between the plasma membrane and the TGN exist for predominantly TGN proteins as well as those that normally cycle to other intracellular compartments. They also demonstrate that addition of BFA not only alters the morphology and localization of the TGN but also the kinetics of endocytosis. PMID- 8443413 TI - Cell cycle expression of two replicative DNA polymerases alpha and delta from Schizosaccharomyces pombe. AB - We have investigated the expression of two Schizosaccharomyces pombe replicative DNA polymerases alpha and delta during the cell cycle. The pol alpha+ and pol delta+ genes encoding DNA polymerases alpha and delta were isolated from S. pombe. Both pol alpha+ and pol delta+ genes are single copy genes in haploid cells and are essential for cell viability. In contrast to Saccharomyces cerevisiae homologs, the steady-state transcripts of both S. pombe pol alpha+ and pol delta+ genes were present throughout the cell cycle. Sequence analysis of the pol alpha+ and pol delta+ genes did not reveal the Mlu I motifs in their upstream sequences that are involved in cell cycle-dependent transcription of S. cerevisiae DNA synthesis genes as well as the S. pombe cdc22+ gene at the G1/S boundary. However, five near-match Mlu I motifs were found in the upstream region of the pol alpha+ gene. S. pombe DNA polymerases alpha and delta proteins were also expressed constantly throughout the cell cycle. In addition, the enzymatic activity of the S. pombe DNA polymerase alpha measured by in vitro assay was detected at all stages of the cell cycle. Thus, these S. pombe replicative DNA polymerases, like that of S. pombe cdc17+ gene, are expressed throughout the cell cycle at the transcriptional and protein level. These results indicate that S. pombe has at least two regulatory modes for the expression of genes involved in DNA replication and DNA precursor synthesis. PMID- 8443415 TI - Increased intracellular Ca2+ induces Ca2+ influx in human T lymphocytes. AB - One current hypothesis for the initiation of Ca2+ entry into nonelectrically excitable cells proposes that Ca2+ entry is linked to the state of filling of intracellular Ca2+ stores. In the human T lymphocyte cell line Jurkat, stimulation of the antigen receptor leads to release of Ca2+ from internal stores and influx of extracellular Ca2+. Similarly, treatment of Jurkat cells with the tumor promoter thapsigargin induced release of Ca2+ from internal stores and also resulted in influx of extracellular Ca2+. Initiation of Ca2+ entry by thapsigargin was blocked by chelation of Ca2+ released from the internal storage pool. The Ca2+ entry pathway also could be initiated by an increase in the intracellular concentration of Ca2+ after photolysis of the Ca(2+)-cage, nitr-5. Thus, three separate treatments that caused an increase in the intracellular concentration of Ca2+ initiated Ca2+ influx in Jurkat cells. In all cases, Ca(2+) initiated Ca2+ influx was blocked by treatment with any of three phenothiazines or W-7, suggesting that it is mediated by calmodulin. These data suggest that release of Ca2+ from internal stores is not linked capacitatively to Ca2+ entry but that initiation is linked instead by Ca2+ itself, perhaps via calmodulin. PMID- 8443414 TI - Autophosphorylation of type II CaM kinase in hippocampal neurons: localization of phospho- and dephosphokinase with complementary phosphorylation site-specific antibodies. AB - We have visualized the distribution of autophosphorylated type II CaM kinase in neural tissue with the use of two complementary antibodies: a monoclonal antibody that binds to the alpha and beta subunits of the kinase only when they are autophosphorylated at threonine-286 (287 in beta) and affinity-purified rabbit antibodies that bind to both subunits only when they are not phosphorylated at these residues. We used these antibodies to double-label organotypic hippocampal cultures, detecting the mouse monoclonal antibody with rhodamine and the rabbit polyclonal antibodies with fluorescein. In double-exposed photographs, the ratios of intensities of the two fluorophores revealed the relative proportion of autophosphorylated and nonphosphorylated kinase in individual neurons throughout the cultures. We found that autophosphorylated and nonphosphorylated kinase are colocalized throughout most neurons rather than segregated within distinct cells or subcellular domains. However, the variations in intensity of the two fluorophores indicated that the proportion of autophosphorylated kinase is consistently higher in neuronal somas than in the neuropil. Incubation of the cultures in Ca2+ free medium dramatically reduced both the level of autophosphorylated kinase detected biochemically and the relative intensity of fluorescent staining with the phosphokinase specific monoclonal antibody. These results support the hypothesis that regulation of Ca(2+)-independent CaM kinase activity in vivo occurs by a dynamic equilibrium between autophosphorylation and dephosphorylation and that this equilibrium is maintained, at varying steady state levels, in all parts of neurons. PMID- 8443416 TI - Elevation of cell cycle control proteins during spontaneous immortalization of human keratinocytes. AB - A human line of spontaneously immortalized keratinocytes (SIK cells) has been derived from ostensibly normal epidermis and has proven useful in dissecting molecular changes associated with immortalization. The original cultures had a normal karyotype and a colony forming efficiency of approximately 3% through 10 passages. At passage 15, after which normal strains ordinarily senesce, these cells continued vigorous growth and gradually increased in colony forming efficiency, stabilizing at approximately 30% by passage 40. During the early stage of increasing colony forming efficiency, the cells acquired a single i(6p) chromosomal aberration and 5- to 10-fold increases in expression of the cell cycle control proteins cyclin A, cyclin B, and p34cdc2. Additional chromosomal aberrations accumulated at later passages (i(8q) and +7), but the i(6p) and the increased expression of cell-cycle proteins were maintained, raising the possibility that these features were important for immortalization. Regulation of cell growth and differentiation in the cultures appeared minimally altered compared with normal keratinocytes as judged by their microscopic appearance and generation of abortive colonies, sensitivity to growth suppression by transforming growth factor-beta and tetradecanoylphorbol acetate, and dependence upon epidermal growth factor for progressive growth. PMID- 8443419 TI - Clinico-pathological correlations in meningiomas: a DNA and immunohistochemical study. AB - We have studied 41 meningiomas classified histologically as benign, atypical or anaplastic. There were 26 females and 15 males and the mean age was 53 years. 36 tumours were supratentorial, 4 infratentorial and one spinal. Flow cytometry was performed on paraffin-embedded tissue using a selective staining technique for DNA. The ploidy index of DNA and percentage of cells in the S and G2/M phases were calculated. Results were correlated with clinical, histological and immunohistological data. 16/41 tumours were found to be diploid, 17/41 aneuploid and 8/41 could not be analysed. Significant correlations were found between aneuploid tumours and some qualitative features such as recurrence, pleomorphism, high cellular density, mitotic activity and brain and soft tissue infiltration. A high proliferative index appeared to be associated with clinical aggressiveness. No particular correlation between the expression of cytokeratin and epithelial membrane antigen markers and flow cytometry was found. Our results suggest that DNA flow cytometry in meningiomas may be of value in predicting the behaviour of these neoplasms and confirm that epithelial pattern in meningiomas is not linked to increased anaplasia or poor prognosis. PMID- 8443417 TI - NUP2, a novel yeast nucleoporin, has functional overlap with other proteins of the nuclear pore complex. AB - We have isolated a new gene, NUP2, that encodes a constituent of the yeast nuclear pore complex (NPC). The NUP2 protein sequence shares a central repetitive domain with NSP1 and NUP1, the two previously characterized yeast nucleoporins. Like NUP1 and NSP1, NUP2 localizes to discrete spots in the nuclear envelope, as determined by indirect immunofluorescence. Although the sequence similarity among these three nucleoporins suggests that they have a similar role in the nuclear pore complex, NUP2, in contrast to NSP1 and NUP1, is not required for growth. Some combinations of mutant alleles of NUP1, NSP1, and NUP2 display "synthetic lethal" relationships that provide evidence for functional interaction between these NPC components. This genetic evidence of overlapping function suggests that the nucleoporins act in concert, perhaps participating in the same step of the recognition or transit of macromolecules through the NPC. PMID- 8443418 TI - Specific cross-linking of the proline isomerase cyclophilin to a non-proline containing peptide. AB - A peptide corresponding to an efficient peroxisomal targeting sequence, the carboxy terminal 12 amino acids of PMP20 from Candida boidinii, was employed as an affinity ligand to search for a peroxisomal targeting receptor. Two proteins from yeast extracts with apparent molecular masses of 20 and 80 kDa were detected by chemical cross-linking to radioiodinated peptide. Both proteins were present in cytosolic supernatants. The 20-kDa species did not cross-link to a control peptide with reversed sequence, whereas the 80-kDa protein cross-linked to both peptides. The cross-linking assay was used to purify the 20-kDa protein from Saccharomyces cerevisiae. Partial protein sequencing identified this protein as cyclophilin, the product of the CYP1 gene. This protein, a peptidyl-prolyl cis trans isomerase, is the yeast homologue of the protein that mediates the immunosuppressant effects of the drug cyclosporin A (CsA). Cross-linking of peptide to cyclophilin was inhibited by CsA. The cross-linking of cyclophilin to the PMP20-derived peptide was unanticipated because the peptide contains no prolines. The CYP1-encoded protein was not required to target proteins to peroxisomes because this organelle appeared to be assembled normally in a CYP1 disrupted strain. Furthermore, the final three amino acids of the peptide, which are critical for peroxisomal sorting, were not required for cross-linking to cyclophilin. We conclude that either cyclophilin is playing a nonessential facilitating role in peroxisomal targeting or that the interaction of the targeting peptide to cyclophilin is mimicking an interaction with an unidentified substrate or effector of cyclophilin. PMID- 8443420 TI - Retinal afferents on Golgi-identified vertical neurons in the superior colliculus of the rabbit. A Golgi-EM, degenerative and autoradiographic study. AB - The characteristics and distribution pattern of retinal afferent terminals making synaptic contacts on narrow field vertical neurons in the stratum griseum superficiale of the rabbit superior colliculus were studied using the Golgi-gold substitution technique in combination with either autoradiographic or degenerative methods. At the level of light microscopy, identified gold-toned vertical neurons showed similar features to those previously described by others. Although their axons were frequently seen rising from the basal dendritic tuft, they could also emerge from an apical dendrite, but rarely from the cell body. The electron microscopic study revealed that these neurons received radiolabelled or degenerated profiles with typical features of retinal terminals, while more proximal parts seemed to receive fewer terminals but of larger size. Axo-somatic synaptic junctions were very rare and, interestingly, retinal terminals were not seen forming synapses on the basal dendritic arborization. The present results indicate that the narrow field vertical cells are targets for retinotectal projection. PMID- 8443421 TI - Quantitative histochemistry of phosphorus in the vestibular gelatinous membrane: an electron probe X-ray microanalytical study. AB - Electron probe X-ray microanalysis was used to study the phosphorus concentration in the otolithic gelatinous membrane of the saccule and the utricle with scanning electron microscopy. The otolithic membranes were plunge-frozen in liquid N2 and freeze-dried. Quantitative analysis was carried out with an energy dispersive detector using the peak-to-background ratio method and different concentrations of KH2PO4 salts dissolved in dextran solutions. The otolithic gelatinous membrane consists of a 25-30 microns-thick layer overlying the cilia of the hair cells. Elements detected in the gelatinous membrane are: Na, P, S, Cl, K and Ca. Although Student's t-test did not show significant differences between saccular and utricular concentrations of phosphorus, the distribution of this element in the two organs was different. Regression analysis established that the concentrations of phosphorus in the saccular and utricular gelatinous membrane were dependent. The regression equation was: y = 18.02x2 + 133.9 (r = 0.83, P < 0.05) where y is the concentration of phosphorus in the utricle, and x2 the concentration of phosphorus in the saccule. The findings obtained in the present study could be related to structural differences in organic phosphate residues of the phosphoproteins associated to collagen, or to different polyphosphoinositide turnover rates in the cell membrane. PMID- 8443422 TI - A scanning electron microscopic study of the oviduct of the toad, before and during ovulation. AB - The surface features of the oviduct of the toad, Bufo melanostictus, was studied under the scanning electron microscope. The epithelial folds show regional variations, being longitudinally disposed in the upper part of the oviduct, spirally arranged in the middle and convoluted in the lower part. There is an abundance of cilia through the oviduct except in the ovisac. Goblet cells are interspersed among the epithelial cells. In between the epithelial folds are openings of tubular secretory glands. During ovulation, there is patchy loss of cilia throughout the oviduct. Most of the goblet cells are empty. On the surface, the cilia are matted together by secretory material which are laid down in layers. PMID- 8443423 TI - Peptidergic (VIP) nerves in normal human pancreas and in pancreatitis: an immunohistochemical study. AB - Vasoactive intestinal polypeptide was demonstrated in the nerves of the human normal pancreas and in pancreatitis by light microscope immunohistochemical technique. In specimens of normal pancreas, vasoactive intestinal polypeptide immunoreactive neuronal cells were present in the autonomic ganglia. These ganglia were found to receive an abundant supply of vasoactive intestinal polypeptide-positive fibre plexuses. Immunoreactive nerve fibres were seen to run in the stroma, in association with secretory acini, ducts and blood vessels. Vasoactive intestinal polypeptide-positive fibres were also seen close to the Langerhans' islets, but no vasoactive intestinal polypeptide-like immunoreactivity was observed in the endocrine cells. In specimens from patients affected by pancreatitis, even in lesioned regions, immunoreactive elements were extremely scarce. PMID- 8443424 TI - Gonadotrophin-releasing hormone immunoreactivity in the brain of the tropical freshwater fish, Pygocentrus notatus (Teleostei-Characidae). AB - The distribution of GnRH in the brain of the teleost Pygocentrus notatus was demonstrated with the avidin-biotin peroxidase immunocytochemical method using highly specific antibody against synthetic mammalian GnRH. Optimal immunoreaction was obtained using: 1) Bouin's fluid for fixation; 2) repeated incubation with primary antiserum; 3) the use of a detergent in the dilution buffer; 4) the high sensitivity of the avidin-biotin immunoperoxidase method with the cobalt intensification of 3-3' diaminobenzidine tetrahydrochloride; and 5) the use of primary antibody with high specificity. GnRH-immunoreactive (GnRH-ir) in cells and/or axons was observed in all main brain regions. In the forebrain, GnRH-ir was located in a network extending from the caudal part of the olfactory bulb to the telencephalon. GnRH-ir fibres were also observed in the optic tectum, cerebellum and hypothalamus. Two groups of neuronal cell bodies were identified. One group was located in the antero-ventral telencephalon corresponding to the nucleus olfactoretinalis. The second group was found in the rostrodorsal hypothalamus. No GnRH-ir material was detected in the pituitary gland, thus confirming the results of previous studies on brain GnRH-ir distribution obtained by radioimmunoanalysis in this species. These results demonstrate a high degree of similarity between the GnRH systems of P. notatus and other teleost species. PMID- 8443425 TI - Inhibition of gentamicin-induced nephrotoxicity by lithium in rat. AB - Daily intraperitoneal injection of gentamicin in doses of 2, 4 and 10 mg/kg/day for 5 consecutive days produced proximal tubular necrosis in male albino rats as assessed by ultrastructural findings from electron microscopic observations. With respect to nephrotoxicity, aminoglycoside antibiotics (AGs) have been shown to concentrate in the lysosomes of kidney proximal tubular cells to inhibit the activities of phospholipases A and C, including a phospholipidosis, characterized by the formation of myeloid bodies. It has been suggested that the nephrotoxicity of AGs is related to the extent of this phospholipidosis. The concurrent therapy of lithium in doses of 5 and 10 mEq/kg/day, administered subcutaneously, 24 hours prior to gentamicin administration for the same period, proved effective in reducing the gentamicin-induced phospholipidosis in kidney as judged by reduction in lysosomal myeloid bodies to an amount of 26-45 percent. It is well known that lithium interferes with phosphatidylinositol turnover and reduces the cellular availability of myoinositol which is needed for the resynthesis of membrane polyphosphoinositides. Thus, the inhibitory effect of lithium on gentamicin induced nephrotoxicity may be due to interference of lithium with phosphoinositide cycle. PMID- 8443426 TI - Immunohistochemical detection of cell proliferation in gastric carcinomas with the monoclonal antibody Ki-67. A study of 24 cases. AB - The proliferative activity in 24 gastric carcinomas was determined by an immunohistochemical method using monoclonal antibody Ki-67 (ABC method). Immunostained nuclei were counted by two observers through a Nachet NS 1000 image numeriser. Three grades were defined according to stained nuclei percentage (proliferation index Pi = percentage of cells engaged in cellular cycle outside Go): grade 1 (Pi < 20%); grade 2 (20% < Pi < 40%); grade 3 (Pi > 40%). About 60% of tumours were in grade 1 and 10% in grade 3. No correlations were observed between Pi and the following parameters: histological differentiation; parietal extension; presence or absence of metastasis. These results may be compared to the two other available studies of Ki-67 antibody in gastric cancers. Our study also showed a heterogeneous distribution of immunostained nuclei, within each single tumour and from one tumour to another, which has been noted in one previous study and in a similar one we made on colorectal carcinoma. This heterogeneity is the consequence of the variability of carcinomatous cell proliferative activity; an important biological factor in the evaluation of tumoral process. The proliferative activity in gastric carcinomas provides an estimation of tumour dynamics that might be a prospective criterium for tumoral process evaluation. PMID- 8443427 TI - Minute and small early gastric carcinoma with special reference to eosinophil infiltration. AB - The authors examined 25 minute early gastric cancers (EGC) and 13 small EGC in order to investigate the incidence and possible causes for the infiltration of eosinophils. The degree of eosinophil infiltration was higher in tumour stroma than in adjacent normal-appearing mucosa; this correlation was statistically significant (P < 0.001). Tumour-associated tissue eosinophilia (TATE) was not correlated with size, histological type, necrosis of the tumour nor gastritis activity in adjacent non-tumoral mucosa. Electron microscopy, performed in 4 cases of small EGC, showed tumour stromal eosinophils with morphological evidence of activation similar to those described for tissue eosinophils in various disorders. Some tumour cells in intimate contact with activated eosinophils exhibited focal cytopathic changes. TATE represents local inflammation probably leading to tumour cell damage. The immunological role of the eosinophils against tumour cells in vivo deserves further investigation. PMID- 8443428 TI - Distribution of cortico-visual neurons projecting to the pons in the cat. A retrograde labelling study with rhodamine latex microspheres. AB - Injections of the low diffusion retrograde tracer rhodamine latex microspheres were made in the pontine grey matter of the cat in order to study the cortical convergence to the pons. We found a different distribution of cells in the convex surface of the brain hemisphere making ventral or dorsolateral injections. In the first case, cells were grouped in the top of the gyri. In the second case, cells were more frequent in the bottom of the sulci. Our results show a possible retinotopic organization of this projection. PMID- 8443429 TI - Fine structure of the retinal pigment epithelium of the great horned owl (Bubo virginianus). AB - The fine structure of the retinal epithelium (RPE), choriocapillaries and Bruch's membrane (complexus basalis) has been studied by light and electron microscopy in the great horned owl (Bubo virginianus). The RPE consists of a single layer of cuboidal cells joined laterally in the mid to basal region by a series of tight junctions forming part of the blood-ocular barrier. Basally (sclerally) the epithelial cells show numerous deep infoldings while apically (vitreally) a wealth of microvillar processes interdigitate with the photoreceptor cells. Internally the RPE cells display a large vesicular nucleus, plentiful smooth endoplasmic reticulum (SER) and polysomes with only small scattered profiles of rough endoplasmic reticulum (RER). Numerous pleomorphic mitochondria are basally located. In the light-adapted state the melanosomes are located almost exclusively within the apical processes indicating retinomotor movements. Myeloid bodies are numerous and often show ribosomes on their outer surface. Bruch's membrane is typical of avian species in that it is pentalaminate and the lamina densa is displaced towards the choriocapillaris. The choriocapillaris itself is but minimally fenestrated facing Bruch's membrane. Most fenestrations present show a single layered diaphragm while others display a double-layered diaphragm. PMID- 8443430 TI - Involvement of neuropeptides in the regulation of growth, structure and function of the adrenal cortex. AB - Current data on the influence of neuropeptides on the growth, structure and function of cells comprising the hypothalamo-pituitary-adrenal axis were presented and discussed. The action of vasopressin, oxytocin, neurotensin, bombesin, neuropeptide Y, substance P and VIP have been evaluated. The hypothesis has been introduced that in vivo effect of some neuropeptides on the structure and function of the adrenal cortex is mediated by vasopressin. PMID- 8443431 TI - The family of epithelioid vascular tumors. AB - Vascular tumors characterized by proliferation of epithelioid (histiocytoid) endothelial cells with abundant eosinophilic hyaline cytoplasm span a broad spectrum of histologic appearances and behaviour. They can occur in a wide variety of sites, such as soft tissues, skin, bone and visceral organs. On the benign end are the epithelioid hemangiomas (angiolymphoid hyperplasia with eosinophilia), which are composed predominantly of well formed vascular channels, and are frequently accompanied by an infiltrate of lymphocytes and eosinophils. In the literature, they have often been confused with Kimura's disease, an idiopathic allergic-inflammatory condition. There have also been controversies as to whether these lesions are neoplastic or reactive. In the middle of the spectrum are the borderline or low grade malignant epithelioid hemangioendotheliomas, characterized by isolated, cords and nests of epithelioid endothelial cells disposed in a hyaline or myxoid matrix; cytoplasmic vacuoles are common. However, the morphologic variations on this theme are very wide rendering recognition of these tumors difficult sometimes. On the malignant end are highly aggressive epithelioid angiosarcomas showing predominantly solid growth and significant nuclear pleomorphism. In addition, there are also cases showing histologic features straddling the borderline areas between the above three defined categories. In this review, the broad morphologic appearances of these epithelioid vascular tumors are discussed and illustrated. PMID- 8443432 TI - Fine structure of the retinal photoreceptors of the great horned owl (Bubo virginianus). AB - The retinal photoreceptors of the great horned owl (Bubo virginianus) consist of rods, single cones and unequal double cones present in a ratio of about 30:1.2. In the light-adapted state the rods are stout cells which are not felt to undergo retinomotor movements. The rod outer segment consists of a stack of scalloped membranous discs enclosed by the cell membrane. The rod inner segment shows an ellipsoid of mitochondria and a wealth of rough endoplasmic reticulum (RER) and polysomes, Golgi zones and autophagic vacuoles but not hyperboloid of glycogen. Single cones show a slightly tapered outer segment, a heterogenous oil droplet and an ellipsoid of mitochondria at the apex of the inner segment. Double cones consist of a larger chief member which also displays an oil droplet and a slightly smaller accessory member which does not. Both members of the double cone as well as the single cone show a prominent ellipsoid, plentiful polysomes and RER and Golgi zones in the inner segment. Neither single nor double cones possess a condensed paraboloid of glycogen but instead show plentiful scattered glycogen particles. Along the contiguous membranes between accessory and chief cones a few presumed junctional complexes are seen near the external limiting membrane. Judging by their morphology in light-adaptation the cones of this species do not undergo photomechanical movements. Rods and cones (both types) have both invaginated (ribbon) and numerous superficial (conventional) synaptic sites. Rods are more numerous in this nocturnally active bird than is usually noted in avian species. PMID- 8443433 TI - Ultrastructure of granulosa lutein cells from rats fed hexachlorobenzene. AB - Corpora lutea from Sprague-Dawley rats that were orally administered 0.0 (control), 1.0, 10.0, and 100.0 mg/kg hexachlorobenzene (HCB) for 21 days were analyzed by electron microscopy. Granulosa lutein cells (GLC) from animals of the 10.0 mg group showed differences from the cells of animals that served as the controls. Golgi complexes and smooth endoplasmic reticulum appeared more conspicuous, possibly due to dilation resulting from hyperactivity. Free polysomes seemed more prominent in the cells of the 10.0 mg group. The GLC architecture from animals of the 1.0 and 100.0 mg groups was similar to that of the corresponding cells in the control group. Since smooth endoplasmic reticulum is involved in the synthesis of steroid hormones, and that free polysomes are engaged in synthesis of cytoplasmic proteins, it is suggested that HCB at a dose of 10.0 mg/kg given for 21 days may alter the synthetic activity of the GLC of the rat. PMID- 8443434 TI - Epidermoid carcinoma of the lung in stage I: factors of prognostic interest. AB - Factors affecting stage I epidermoid cancer of the lung were studied in a series of 29 patients treated only by surgery and followed up for ten years. A set of 13 variables with a possible influence on prognosis were investigated. The application of the Cox Univariate Analysis to the different variables showed the grade of cell differentiation and the mitotic index to be predictors. In the Cox Multivariate Analysis, the proportional regression equation revealed two independently significant variables (p < 0.01), which were the Mitotic Index and Nuclear Area. Grouping patients on the basis of the prognostic variables indicated allows a better prediction for survival to be made for this series of patients. PMID- 8443435 TI - Cell surface patterns in normal human oral gingival epithelium. A quantitative scanning electron microscopy approach. AB - We used scanning electron microscopy to study the morphological surface patterns of cells that cover the attached gingiva and intervestibular papilla of the human oral gingival epithelium. Five patterns are described on the basis of the overall appearance of morphological surface markers: microvilli, parallel, fingerprint, reticular and pitted. Statistical analyses detected significant differences in the frequency of each pattern in both regions of the oral gingival epithelium, and showed the reticular and fingerprint types to predominate. We propose that our description of the different morphological surface types may be of use as a standard for subsequent cytological studies and characterizations of morphological alterations in diseased gingiva. PMID- 8443436 TI - Matrix production of smooth muscle cells from rat aorta in vitro. AB - Immunofluorescence microscopic methods served to demonstrate the production of the following matrix components in cultures of vascular smooth muscle cells from rat aorta: fibronectin; nidogen; heparan sulphate-proteoglycan (HS-PG); laminin; and collagen types I, III, IV, V, and VI. A time-dependence of synthesis and secretion could be shown for a number of components of the extracellular matrix (ECM), such as laminin. The results revealed the following estimated quantitative differences of the collagen types: type I > type III > types V and VI. A filamentous/fibrillar matrix and also occasionally a typical basal lamina could be demonstrated electron microscopically around the smooth muscle cells. PMID- 8443437 TI - Immunogold identification of the GH cells of goat in different physiological conditions. AB - Growth hormone-containing cells (GH cells) in the anterior pituitary gland of the female goat during anoestrus, pregnancy and lactation were identified by the immunogold complex technique combined with electron microscopy. In the three physiological stages analyzed, most of the GH cells were characterized by a round to oval or triangular shape and the presence of numerous spherical and electron dense secretory granules (300-1,200 nm). Granules with the largest diameters were observed during the lactating stage. In these cells, the rough endoplasmic reticulum (RER) and Golgi complex (GC) were usually poorly developed. Also in lactating animals, a low number of GH cells with more highly developed RER and GC with a few small secretory granules (230-360 nm in diameter) were also observed. This structural configuration suggests that these cells are more active than those with a lower development of cytoplasmic organelles, although their low frequency does not support a considerable increase in hormonal synthesis and release during lactation in comparison with anoestrus and pregnancy stages. PMID- 8443438 TI - Fine structure of the pecten oculi in the great horned owl (Bubo virginianus). AB - The pecten oculi of the great horned owl (Bubo virginianus) has been examined by light and electron microscopy. The pecten in this species is of the pleated type and is small in comparison to the size of the eyeball. It consists of 7-8 accordion folds which are joined apically by a pigmented bridge of tissue. Within each fold are numerous capillaries, larger supply and drainage vessels and plentiful pleomorphic melanocytes. The capillaries are extremely specialized vessels, most of which display plentiful microfolds on both their luminal and abluminal surfaces although some capillaries show but a few microfolds. The endothelial cell bodies are extremely thin with most organelles located near the nucleus. All capillaries are surrounded by a thick fibrillar basal lamina which is felt to be structurally important. Pericytes are a common feature within these thickened basal laminae. The numerous melanocytes form an incomplete sheath around the capillaries and are also presumed to be fulfilling a structural role. While the morphology of the pecten in the great horned owl is certainly indicative of a heavy involvement in transport, when compared to the pecten in species that are more visually oriented it is smaller, displays fewer folds and a reduced number of microfolds within the capillaries. PMID- 8443439 TI - Experimental reproduction of acute pneumonic pasteurellosis in rabbits. AB - A histomorphometric and physiopathological study was made of the lung parenchyma of Belgian White SPF rabbits infected experimentally with Pasteurella multocida type A. Symptoms observed were characteristic of the acute respiratory syndrome. Mean serum cortisol concentration and rectal temperature increased in all experimental groups. Histopathological changes included alveolitis and leukocytic bronchitis. Changes in alveolar and bronchial cytoarchitecture were attributed to the degeneration and necrosis of constituent epithelial cells. PMID- 8443440 TI - Epidemiology and clinical manifestations of Lyme borreliosis in childhood. A prospective multicentre study with special regard to neuroborreliosis. AB - Lyme borreliosis is a tick-borne infection caused by the spirochete Borrelia burgdorferi, whose discovery in 1982 solved an aetiological mystery involving a variety of dermatological and neurological disorders and explained their association with Lyme disease. Lyme borreliosis occurs frequently and is readily treatable with antibiotics. Along with its discovery, however, came the realization that it is difficult to diagnose accurately, especially antibody diagnosis. False-positive antibody results in particular led to gradual widening of the clinical spectrum, and differential diagnosis became increasingly difficult. This prospective, multicentre study presents a systematic description of Lyme borreliosis in childhood, emphasizing epidemiological and clinical issues. Because, predominantly, inpatients were examined, Lyme neuroborreliosis was the focus of the study, with the chief concern being to minimize false positive results. To this end, we chose to narrow the diagnostic criteria, using the presence of specific antibodies in the cerebrospinal fluid as the determining factor. The epidemiological investigation was focused on the incidence of Lyme neuroborreliosis in childhood in southern Lower Saxony as well as on the prevalence of Lyme neuroborreliosis among acute-inflammatory neurological illnesses in children. The clinical part of the study aimed at establishing criteria for differential diagnosis in addition to the detection of specific antibodies. The detection of specific IgM antibodies using an IgM capture ELISA confirmed the presence of acute Lyme borreliosis. The study examined 208 children with Lyme borreliosis, of whom 169 had Lyme neuroborreliosis, from mid-1986 until the end of 1989. The yearly incidence of Lyme neuroborreliosis in Lower Saxony was 5.8 cases/100,000 children aged 1 to 13. The manifestation index was 0.16, or one case of Lyme neuroborreliosis per 620 infected children, compared with the presence of specific antibodies against B. burgdorferi for children in the same age group and region. Both the seasonal distribution of Lyme borreliosis, which peaked in summer and autumn, as well as the information about when the tick bites took place point to an incubation period of a few weeks. The most frequent manifestation of Lyme neuroborreliosis in childhood was acute peripheral facial palsy, found in 55% of all cases (n = 93). Lyme borreliosis proved to be the most frequently verifiable cause of acute peripheral facial palsy in children, causing every second case of this disorder in summer and autumn.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8443441 TI - [The value of the prism adaptation test in determining the degree of squint surgery]. AB - The angle of squint deviation was measured preoperatively before and after a prism adaptation of 1 day's duration in 50 esotropic and 45 exotropic patients. All had a deviation of 17 degrees or more under prismatic correction and were operated on by a recess-resect procedure of 10 mm on one eye. Postoperative measurements were done about 4 days and 6 weeks after surgery. In 58% of the esotropic and 37% of the exotropic patients, the initial deviation increased under prisms. This was found most often when normal retinal correspondence was present. There was a correlation between the effect of surgery with the change of deviation under prisms, particularly in normosensory esotropia and intermittent exotropia. Accordingly, the standard deviation of the surgical effect was smaller in this group, when it was calculated from the deviation under prisms in comparison to a calculation from the primarily measured angle. The influence of the preoperative deviation on the effect of a 10-mm recess-resect procedure was also found for the deviation under prisms and must therefore additionally be mentioned in the dosage of surgery. This retrospective study shows that preoperative prism adaptation improves predictability of the effect in squint surgery, at least in normosensory esotropia and intermittent exotropia. In patients with early-onset strabismus prism adaptation does not improve predictability, but higher dosage seems to be useful in cases with increased deviation under prisms and did not lead to over corrections. In this group the test represents an additional method for evaluation of the binocular sensory status. PMID- 8443442 TI - [Recurrent canaliculitis and dacryocystitis as a sequela of persistent infection with Chlamydia trachomatis]. AB - We report on 4 patients aged 39-62 years with follicular conjunctivitis, canaliculitis, canalicular obstruction, dacryocystitis and nasolacrimal duct obstruction caused by chronic oculogenital infection with Chlamydia trachomatis. Microbiological diagnosis was accomplished by means of the McCoy cell culture technique as a highly specific tool for detection of the chlamydial infection. In addition, serological tests (IgA-IPA and IgG-IPA techniques) were performed. Bacteriological examination of conjunctival smears showed coinfection in 3 patients (Proteus mirabilis in 1, Staphylococcus aureus coagulase-positive in 3). Despite successful operation techniques, the obstructive inflammation caused by oculogenital chlamydial infection could only be cured by systemic treatment with specific antibiotics, such as doxycycline or erythromycin. All cases of chronic follicular conjunctivitis with lacrimal inflammation that are resistant to topical antibiotics should suggest the possibility of infection with Chlamydia trachomatis. PMID- 8443443 TI - [Effective vision screening can decrease the rate of amblyopia]. AB - The quality of screening for testing visual disorders is unsatisfactory. Diagnosis and therapy are generally too late to exploit the advantage therapy can give during the sensitive period of visual acuity. About 10% of the adult population show decreased visual acuity (below 0.8). These persons have a more or less distinct amblyopia. Commonly used visual acuity tests do not allow the crowding phenomenon to be measured, although it is an easily measurable amblyopia characteristic. The most frequently used visual acuity test by German health authorities (R 5/R 11 test with plate No. 120) shows 48% false-negative results. We introduced the H test for preschool children. For school children and adults we developed the C test. To detect amblyopia precisely we designed both tests so that the crowding phenomenon could be measured. Both tests were validated in more than 700 subjects. All persons received an extensive ophthalmological checkup, which was used as the reference for normality. The H test is based on the matching principle and works with musical feedback. The test can be used from the age of 3 years onward. Therefore, the advantage of early therapy can be fully exploited. The H test has a 3% percentage false-negative rate. The C test is based on the Landolt ring. The visual acuity charts are presented as a book (40 cm distance) for measuring near visual acuity and (5 m) for measuring distance visual acuity. The C test has less than 5% false-negative results. Both tests can help in different age groups to diagnose amblyopic cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8443444 TI - [Surgical and conservative treatment of lagophthalmus (facial paralysis). II]. AB - Thirty patients with irreversible facial palsy were treated with gold implants from 0.5 to 1.8 g. For the immediate treatment of postoperative facial palsies and reversible kinds of lagophthalmos, lead weights of 1.2 to 1.8 g ("lid dynamic eye dressing") are preferred to hourglass dressings. Insufficient orbicularis muscle function is compensated by the weight. The observation time for gold implants is more than 2 years; the fixation time of the adhesive lead weights is 1 to 10 days. Tolerance is excellent to both treatments. The principle is gravity dependent and is limited to the vertical and oblique head position. For sleeping at night, ointment application and pressure on the upper lid by a pillow are advisable; an additional hourglass dressing is possible. No serious keratopathies were seen in any cases. All patients found the return of lid motility from the restored levator muscle function to be a functional and cosmetic advantage. After weighing the advantages and disadvantages, especially the operative/technical expense in relation to the effective results, it would appear that simple lid loading is so far the best method of treating lagophthalmos. PMID- 8443445 TI - [Mechanism of the formation of orbital floor fractures. Holographic interferometry studies]. AB - To date, it has not been possible to answer the question of whether in the classic blow-out fracture the orbital floor is fractured by hydraulic force exerted by the orbital contents or by force transmission within the bony structures of the skull. The aim of our investigation was therefore to reveal the nature of orbital deformation mediated solely by the bone. In holographic interferometry the holographic image of the unstrained object is superimposed on the image of the same object after deformation. The resulting image of the object contains a pattern of interference lines representing the extent of the deformation. This image can be visualized on a TV screen after digital processing of a picture registered by a video camera. This method was used to analyze the deformation of the bony orbit by contact force applied to several points along the orbital rim (each application consisting of 1 N) and by strain distributed evenly upon the orbital rim of the human skull. In all cases maximal deformation occurred in the medial part of the orbital floor no matter where the stress was applied. This finding coincides with the fact that the majority of clinically diagnosed fractures are found in this area. In conclusion, force transmission within the bone is considered as being one determining factor for occurrence of orbital floor fractures. PMID- 8443446 TI - [Excimer laser sclerostomy of secondary glaucoma]. AB - Initial results after nine ab externo sclerotomies on seven patients awaiting enucleation because of intensive pain caused by secondary glaucoma have encouraged us to present the methods used for this technique of fistula construction and the course in these patients. A special applicator permits precise manual positioning of the excimer laser beam (lambda = 308 nm) subconjunctivally at the limbus using a quartz-quartz fiber (diameter: 0.32 mm). The energy applied at the fibertip is 4 mJ per pulse, with a repetition rate of 80 Hz. All patients undergoing the operation, which lasted only a few minutes, were treated as out-patients without a retrobulbar anaesthesia. Because of the minimal irritation of the anterior chamber, only antibiotic treatment was required after the operation. The intraocular pressure immediately decreased to normal levels after the operation without any further glaucoma treatment in five cases. In the other two cases reduced, but still minimally elevated, pressure was recorded. In the case of one heavily inflamed eye, which had been subjected to two operations, pain felt by the patient was relieved when the pressure was reduced. The maximum period of post-operative follow-up so far is over 10 months and the decrease of intraocular pressure has remained adequate without any additional antiglaucoma therapy. In all cases enucleation was avoided. PMID- 8443447 TI - [Experimental laser sclerostomy ab externo with erbium:YAG laser]. AB - A fistula from the anterior chamber of the eye into the subconjunctival space can be created by external laser application (laser sclerostomy). A pulsed (200 microseconds) Erbium-YAG laser was used because of the high scleral absorption. The laser energy was applied via a special fiber, which was inserted into a special application cannula to guide it into the subconjunctival space. A total of 24 rabbit eyes were treated and examined histologically after various postoperative periods. In all cases a functioning fistula and a marked reduction of the IOP (mean value 13 mmHg to 2 mmHg) were detected. On average, 60 mJ was required. The zone of thermal damage was limited to 40 microns. Cornea and lens showed no evidence of damage after 1 day or after 4 weeks. In the rabbit model, the fistulas were closed within 2 weeks, and long-term persistence of the fistula must therefore be verified in a clinical study. The method presented is minimally invasive, requires only a short operation time, causes minimal trauma to the conjunctiva, and may become an alternative to traditional fistulization operations. PMID- 8443448 TI - [Disordered peripapillary microcirculation in glaucoma patients]. AB - To study the haemodynamics of the peripapillary choroid, perfusion pressure videoangiography (PVA) was performed in six healthy subjects and in seven patients with primary open-angle glaucoma (poag). In healthy subjects the peripapillary part of the choroid starts filling at distinctly lower ocular perfusion pressures than other parts of the choroid. The mean difference in perfusion pressure between peripapillary and perimacular filling was 13.6 mmHg in the six healthy subjects. A different filling pattern of the choroid was found in the seven glaucoma patients. The mean difference in perfusion pressure between the beginning of peripapillary and the beginning of perimacular perfusion of the choroid was found to be as small as 1.9 mmHg. That the filling of the peripapillary choroid observed by PVA in healthy subjects is found to start at lower perfusion pressures than in the other parts is explained by autoregulative dilatation of the peripapillary choroidal arterioles resulting from artificially raised intraocular pressure during the PVA examination. In the poag patients the peripapillary choroidal arterioles were dilated either insufficiently or not at all. The following conclusions are drawn: (1) The peripapillary choroid of healthy persons shows effective autoregulation securing the blood supply to the prelaminar part of the optic nerve. (2) In poag the peripapillary choroid has lost the capability of effective autoregulation. PMID- 8443449 TI - [Physical technical calibration of a new self-tonometer]. AB - The microprocessor-controlled applanation tonometer was calibrated in force measurement and area detection by using weights and silicon calibration pistons. This makes it possible to compare the technical precision of the instrument under standardized conditions and the results of previous clinical examinations. With the instrument in a vertical position, the force measurements meets the official calibration requirement. Force measurements in a horizontal position will follow in order to demonstrate that exact measurements can be taken with the instrument irrespective of position. A suitable method for calibrating the optical sensor by using the silicone pistons for area detection is shown. This method is to be extended by using calibration pistons of different diameters, which are within the permitted calibration tolerances. PMID- 8443450 TI - [Optimizing the automatic self-tonometer by an acoustic control signal and changed fixation optics]. AB - An automatic self-tonometer must fulfill special requirements from the point of view of precision as well as user-friendliness. The sensor that applanates the cornea must be perfectly centered on the vertex in order to measure the intraocular pressure correctly. The modified version of the self-tonometer has been equipped with an acoustic control signal and a modified fixation lamp that facilitate its use. In order to analyze the effectiveness of these hardware changes, we compared the modified tonometer to the existing self-tonometer in a randomized study with 30 patients. Reference was the Draeger hand-held applanation tonometer. The results show comparable precision; however, the percentage of error measurements in the modified tonometer was considerably lower. This is a definite improvement in the development of the self-tonometer. PMID- 8443451 TI - [Eye burns caused by wolf's milk]. AB - If the sap of Euphorbia inadvertently gets in the eye, it can cause conjunctivitis, keratitis or iritis. Therapy consists of rinsing, antibiotics, steroids and mydriatics when the anterior chamber is inflamed. It may also be necessary to protect the damaged eye from light, because photoallergic reactions are possible. PMID- 8443452 TI - [The 4-prism diopter base-in test in diagnosis of exophoria with asthenopia and compensation by accommodative convergence]. AB - About 30% of our patients suffering from purely binocular asthenopia showed lower binocular than monocular visual acuity. Cover test examination revealed exophoria at near fixation, which could be regarded to be physiological. Furthermore, the Pola test as well as Graefe's prism diplopia test showed no pathological findings. When given 4 prism base-in, a better binocular acuity was achieved and exophoria at for distance fixation was revealed. Often the prisms base-in had to be increased slowly and an operative treatment was indicated in 80%. The test is described in detail and examples from typical case studies are demonstrated. The importance of the test for understanding asthenopia in cases with heterophoria is discussed. PMID- 8443453 TI - [Results of treatment in malignant epithelial conjunctival tumors]. AB - Tumors of the conjunctiva are rare, especially malignant epithelial tumors. Although these tumors grow very slowly and only exceptionally with local invasion, intensive treatment is necessary. We studied the results of combined treatment with excision and brachytherapy with strontium-90 in 30 patients with carcinoma in situ and squamous cell carcinoma. After a follow-up between 3 months and 8 years (average 3 years) only one patient suffering from a squamous cell carcinoma developed a recurrence after 1 year. Two patients with squamous cell carcinoma developed telangiectasis, one patient developed glaucoma, and one patient developed a scleral ulcer. PMID- 8443454 TI - [Immunocytochemical and ultrastructural studies of human scleral spur. Characterization of a contractile cell population]. AB - Contraction of the ciliary muscle induced by cholinergic drugs causes movement of the scleral spur and separation of the trabecular meshwork lamellae. The effect of epinephrine, however, does not seem to be mediated by ciliary muscle tone. We investigated the scleral spur in 37 human eyes (age 17-87 years). Serial tangential sections were studied with ultrastructural and immunocytochemical methods. The ciliary muscle cells do not enter the scleral spur, but their tendons, which consist of elastic fibers, are continuous with the elastic fibers in the scleral spur. Within the scleral spur is found a population of circularly oriented and spindle-shaped cells. The scleral spur cells form no bundles, but are loosely aggregated. They have long cytoplasmic processes and are connected to each other by adherence type and gap junctions. The scleral spur cells show intense staining for smooth-muscle-specific alpha-actin and myosin. Ultrastructurally, the scleral spur cells contain abundant actin filaments, but otherwise do not show the typical ultrastructure of ciliary muscle cells. The scleral spur cells do not express a complete basal lamina. They form individual tendinous connections with the elastic fibers in the scleral spur, which are continuous with the elastic fibers of the trabecular meshwork. The scleral spur cells are in close contact with nerve terminals containing small granular vesicles that are typical for adrenergic terminals. We conclude that the scleral spur cells are contractile myofibroblasts. Their contraction might be involved in the effects of epinephrine on the aqueous outflow. PMID- 8443455 TI - [Plasminogen activator and PAI. Detection in aqueous humor of the human eye]. AB - Tissue-type plasminogen activator (t-PA), a serine protease that catalyzes the conversion from plasminogen to plasmin, plays an important role in the fibrinolytic system and has also in recent years attracted attention in the field of ophthalmology. In order to examine the role of t-PA in the physiology of the anterior segment, we detected t-PA in aqueous humor by using immunoassays. The samples were taken by keratocentesis prior to cataract or glaucoma surgery. The sample volumes ranged from 50-200 microliters. The quantities of t-PA Ag and plasminogen-activator inhibitor (PAI) Ag were determined by using enzyme-linked immunosorbent assays. We determined t-PA and PAI in the aqueous humor of 54 patients between 32 and 87 years of age. The t-PA Ag levels ranged from 0.2 to 1.9 ng/ml (average 0.8 ng/ml), PAI-Ag from 0.2 to 1.7 ng/ml (average 0.9 ng/ml). The values measured in men were slightly higher than those measured in women. No association between t-PA and PAI levels and accompanying diseases or metabolic disorders was noted. Precise knowledge about the presence of t-PA in aqueous humor is a prerequisite for the recognition of pathological events following intraocular fibrin formation and may be an important basis for the therapeutic use of rt-PA in the intraocular inflammatory process. PMID- 8443456 TI - [Long-term results of argon laser trabeculoplasty. An overview]. PMID- 8443457 TI - Nurse abuse in Saskatchewan: a study. PMID- 8443458 TI - Expectations for participative decision making. PMID- 8443459 TI - The environment and work performance. PMID- 8443460 TI - Dress codes: who needs them? PMID- 8443462 TI - New curriculum for AIDS education. PMID- 8443461 TI - The challenges of change. PMID- 8443463 TI - Saskatchewan Registered Nurses' Association. Position paper on use of restraints in client care. PMID- 8443464 TI - Liability protection for registered nurses. PMID- 8443465 TI - Systemic elimination of macrophages using liposomes does not prevent the induction of type I diabetes. AB - Silica treatment of experimental animals leads to a prevention of genetically determined or experimentally induced type I autoimmune diabetes. Since silica is toxic for macrophages an important involvement of these cells in the onset of the disease was concluded. Here we show that in vivo elimination of macrophages by liposome treatment does not lead to prevention of streptozotocin-induced diabetes. The results indicate that the presence of mature macrophages is not an important requisite for diabetes induction and that the effects of silica treatment must be attributed to activation of macrophages leading to disturbed cytokine levels, or to effects on other cell types. PMID- 8443466 TI - Immunogenicity of various beta-lactam antibiotic-protein conjugates and cross reactivity of the antibodies produced in guinea pig. AB - Immunogenic properties of bovine serum albumin (BSA) conjugates of various beta lactam antibiotics (ABs) and cross-reactivity of the produced antibodies were investigated in guinea pigs. Each AB-BSA conjugate was immunized with complete Freund's adjuvant. Following the second injection, AB-specific antibodies were detected with high titers. Produced antibodies showed concentration-dependent inhibition by the corresponding AB. Cross-reactivity between the produced antibodies and ABs was evaluated with two methods, i.e. by testing for reactivity with the various AB-ovalbumin conjugates, and by assaying for inhibition of enzyme-linked immunosorbent assay (ELISA) by the various ABs. The latter method could detect minor cross-reactions more sensitively than the former one. The results suggested that similarity of the acyl side chain of a cephalosporin nucleus or a penicillin nucleus contributes to immunological cross-reactivity. PMID- 8443467 TI - Serum bactericidal activity and induction of chemiluminescence of polymorphonuclear leukocytes: complement activation pathway requirements in defense against Neisseria meningitidis. AB - Serum bactericidal activity and chemiluminescence (CL) responses of polymorphonuclear leukocytes (PMNL) to pathogenic Neisseria meningitidis serogroups B and W-135 and to nonpathogenic serogroup 29E were examined with pooled normal human serum depleted of the complement proteins C1q, factor D, properdin and C5. Purified C1q, factor D, properdin and C5 were added alone or in combination. For investigation of serogroup W-135 meningococci, a C1q, factor D and properdin-depleted postvaccination serum with high concentrations of anticapsular antibodies was also used. Serogroup B and W-135 cultured to log phase were resistant to the bactericidal activity of pooled normal human serum but were efficiently killed through the classical pathway alone when the bacteria were cultured to stationary phase. Nonpathogenic serogroup 29E meningococci in log or stationary growth phases were efficiently killed in serum, predominantly through the classical pathway. Serogroup W-135 meningococci grown to log phase were resistant to classical pathway-mediated bactericidal activity in postvaccination serum but were killed on addition of alternative pathway proteins. Stationary phase serogroup W-135 meningococci were killed through both pathways in the postvaccination serum. In the pooled normal human serum CL responses of PMNL were consistently more pronounced with fully reconstituted C1q, factor D, properdin, C5-depleted serum than with serum reconstituted with C1q, factor D and properdin suggesting contribution of actions related to terminal components. In the absence of C1q, serogroup W-135 meningococci in postvaccination serum induced a significant but delayed alternative pathway mediated CL response. CL responses induced by serum-opsonized meningococci, in contrast to serum bactericidal activity, were not influenced by culture conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8443468 TI - Complement activation and C3 allotype distribution in patients with bronchial asthma. AB - 61 patients suffering from intrinsic (idiotypic) or extrinsic (allergic) asthma were investigated for signs of complement activation and for C3 phenotype distribution. Activation of both the classical and alternative pathway of the complement system and generation of the membrane attack complex could be assessed by ELISAs for the activation-specific protein-protein complexes C1rsC1 inhibitor, C3b(Bb)P and SC5b-9, respectively. A possible deficiency of the complement regulatory proteins C1 inhibitor, factor H and factor I was excluded. In contrast to earlier studies, C3 allele frequencies did not differ from those found in the healthy population. Our results support the role of complement activation during bronchial asthma and, thereby, provide further evidence for the inflammatory nature of the disease. PMID- 8443469 TI - The effect of aspirin on mononuclear cells in aspirin-sensitive asthmatics and control subjects. AB - Three groups, comprising normal subjects (n = 10), aspirin-sensitive asthmatics (ASA+; n = 10) and aspirin-insensitive asthmatics (ASA-; n = 10) were entered into a blinded, parallel group study to asses the modulating effect of aspirin (ASA; 0.0275, 0.275, 1.385, 2.75, 6.9, 13.8 and 27.5 microM) on lymphocyte proliferation in vitro, either alone or in combination with the mitogen, phytohemagglutinin (PHA; 10, 25, 50, 100, 200 and 500 micrograms/ml). The percentage and absolute numbers of CD4-positive T cells (normals: 51.3%; ASA+: 51.1%; ASA-: 46.1%; p = 0.4038) and CD8-positive T cells (normal: 27.5%; ASA+: 26.4%; ASA-: 28.4%; p = 0.8408) did not differ significantly between the groups. Significant differences in mean PHA responses between ASA+, ASA- and normal subjects were observed when peripheral blood lymphocytes (PBL) were exposed to PHA concentrations over the range 10-50 micrograms/ml; PHA 10 micrograms/ml (p < 0.005), PHA 25 micrograms/ml (p < 0.005) and PHA 50 micrograms/ml (p < 0.01), the lowest and highest proliferative responses being obtained with PBL from ASA+ and ASA-, respectively. However, at higher PHA concentrations (100-500 micrograms/ml), differences between the three groups were not observed. When ASA was added in combination with PHA, augmentation of the PHA response was observed with cells from all three groups but was most marked in the ASA+ group, especially at lower PHA concentrations (10-50 micrograms/ml) in combination with 0.275-13.8 microM ASA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8443470 TI - Inhibition of IgE-mediated leukotriene generation and bronchoconstriction in primates with a new 5-lipoxygenase inhibitor, E6080. AB - The inhibitory effects of a novel compound, 6-hydroxy-2-(4-sulfamoylbenzylamino) 4,5,7-trimethylbenzothiazo le hydrochloride (E6080) on IgE-mediated reactions in vitro and in vivo were determined in rhesus monkeys. E6080 inhibited both antigen and anti-human IgE-induced leukotriene C4 generations from lung fragments at similar concentrations: the IC50s of E6080 were 1.11 and 0.96 microM, respectively. AA861 also inhibited both leukotriene C4 generations with IC50s of 0.79 and 0.76 microM, respectively. All 9 monkeys demonstrating positive cutaneous reactivity against Ascaris antigen at < 10(-7) g protein/0.1 ml showed reproducible bronchoconstriction upon aerosolized antigen challenge, but 5 monkeys demonstrating weak or no reactivity to the antigen at levels > 10(-5) g protein/0.1 ml showed no significant bronchoconstriction. The high responder monkeys showed a marked increase in lung resistance (RL 335.3 +/- 85.3%, n = 11) and a decrease in dynamic lung compliance (67.7 +/- 4.2%, n = 11) after antigen challenge following pretreatment with diphenhydramine. These pulmonary changes lasted for more than 30 min. E6080 at oral doses of 3 and 10 mg/kg showed dose dependent inhibition of both pulmonary changes. Ten milligrams per kilogram of E6080, administered 1.5 h prior to antigen challenge, significantly inhibited the changes in both parameters, while 3 mg/kg showed significant inhibition of only the RL change. These results demonstrate that E6080 inhibited immunologically stimulated leukotriene production in the lung, resulting in inhibition of the antigen-induced airway response in primates. PMID- 8443471 TI - Vaccines in AIDS. Present state of knowledge. AB - The identification of a virus, HIV-1, as the etiological agent of AIDS has opened the door to the development of a vaccine against this disease, for both prophylactic and therapeutic purposes. A number of different vaccine strategies have been developed in pursuit of this aim. The first major advances in this direction were the reports that some candidate vaccines could prevent infection of chimpanzees with HIV-1. Human trials have now been initiated in HIV-1 seronegative and seropositive individuals and the details of the vaccine strategies involved and the results obtained to date are described. PMID- 8443472 TI - How many doctors does Britain need by 2010? PMID- 8443473 TI - On not achieving a balance. PMID- 8443474 TI - Liver failure induced by paracetamol. PMID- 8443475 TI - Endometriosis. PMID- 8443476 TI - Maintaining the treatment of mentally ill people in the community. PMID- 8443477 TI - Respite care. PMID- 8443478 TI - Gallo guilty of AIDS misconduct. PMID- 8443479 TI - Double blind clinical and laboratory study of hypoglycaemia with human and porcine insulin in diabetic patients reporting hypoglycaemia unawareness after transferring to human insulin. AB - OBJECTIVES: To compare awareness of hypoglycaemia and physiological responses to hypoglycaemia with human and porcine insulin in diabetic patients who reported loss of hypoglycaemia awareness after transferring to human insulin. DESIGN: Double blind randomised crossover study of clinical experience and physiological responses during slow fall hypoglycaemic clamping with porcine and human insulin. SETTING: Clinical investigation unit of teaching hospital recruiting from diabetes clinics of five teaching hospitals and one district general hospital. SUBJECTS: 17 patients with insulin dependent diabetes mellitus of more than five years' duration who had reported altered hypoglycaemia awareness within three months of transferring to human insulin. MAIN OUTCOME MEASURES: Glycaemic control and frequency of hypoglycaemic episodes during two months' treatment with each insulin. Glucose thresholds for physiological and symptomatic responses during clamping. RESULTS: Glycaemic control did not change with either insulin. 136 hypoglycaemic episodes (eight severe) were reported with human insulin and 149 (nine severe) with porcine insulin (95% confidence interval -4 to 2.5, p = 0.63). 20 episodes of biochemical hypoglycaemia occurred with human insulin versus 18 with porcine insulin (-0.8 to 1, p = 0.78). During controlled hypoglycaemia the mean adrenaline response was 138 nmol/l/240 min for both insulins; neurohormonal responses were triggered at 3.0 (SE 0.2) versus 3.1 (0.2) mmol/l of glucose for adrenaline and 2.5 (0.1) versus 2.5 (0.1) mmol/l for subjective awareness. CONCLUSIONS: These data suggest that human insulin per se does not affect the presentation of hypoglycaemia or the neurohumoral, symptomatic, and cognitive function responses to hypoglycaemia in insulin dependent diabetic patients with a history of hypoglycaemia unawareness. PMID- 8443480 TI - Umbilical cord clamping and preterm infants: a randomised trial. AB - OBJECTIVE: To investigate the clinical effects of regulating umbilical cord clamping in preterm infants. DESIGN: A prospective randomised study. SETTING: The Queen Mother's Hospital, Glasgow. SUBJECTS: 36 vaginally delivered infants over 27 and under 33 weeks' gestation. INTERVENTION: Holding the infant 20 cm below the introitus for 30 seconds before clamping the umbilical cord ("regulated" group, 17 patients), or conventional management ("random" group, 19 patients). MAIN OUTCOME MEASURES: Initial packed cell volume, peak serum bilirubin concentrations, red cell transfusion requirements, and respiratory impairment (assessed by ventilatory requirements, arterial-alveolar oxygen tension ratio over the first day in ventilated infants, and duration of dependence on supplemental oxygen). RESULTS: There were statistically significant differences between the two groups in mean initial packed cell volume (regulated group 0.564, random group 0.509) and median red cell transfusion requirements (regulated group zero, random group 23 ml/kg). 13 infants from each group underwent mechanical ventilation and showed significant differences in mean minimum arterial-alveolar oxygen tension ratio on the first day (regulated group 0.42, random group 0.22) and in median duration of dependence on supplemental oxygen (regulated group three days, random group 10 days). Differences in final outcome measures such as duration of supplemental oxygen dependence and red cell transfusion requirements were mediated primarily through arterial-alveolar oxygen tension ratio and also packed cell volume. CONCLUSIONS: This intervention at preterm deliveries produces clinical and economic benefits. PMID- 8443481 TI - Comparison of reduction in microalbuminuria by enalapril and hydrochlorothiazide in normotensive patients with insulin dependent diabetes. AB - OBJECTIVE: To compare the effects of sodium depletion and of angiotensin I converting enzyme inhibition on microalbuminuria in insulin dependent diabetes. DESIGN: Randomised, double blind, double dummy parallel study of normotensive diabetic patients with persistent microalbuminuria (30-300 mg/24 h) treated with enalapril or hydrochlorothiazide for one year after a three month, single blind placebo period. SETTING: Diabetic clinic in a tertiary referral centre. PATIENTS: 10 diabetic patients with low microalbuminuria (30-99 mg/24 h) and 11 with high microalbuminuria (100-300 mg/24 h). INTERVENTIONS: 11 subjects (six with low microalbuminuria, five with high microalbuminuria) were given enalapril 20 mg plus placebo hydrochlorothiazide once daily and 10 (four with low microalbuminuria, six with high microalbuminuria) hydrochlorothiazide 25 mg plus placebo enalapril once daily. MAIN OUTCOME MEASURES: Monthly assessment of urinary albumin excretion and mean arterial pressure; plasma active renin and aldosterone concentrations and renal function studies at 0, 6, and 12 months. RESULTS: Median urinary albumin excretion decreased from 59 (range 37-260) to 38 (14-146) mg/24 h with enalapril and from 111 (33-282) to 109 (33-262) mg/24 h with hydrochlorothiazide (analysis of variance, p = 0.0436). During the last three months of treatment with enalapril five patients had persistent normoalbuminuria (2-3 times below 30 mg/24 h), five low microalbuminuria, and one high microalbuminuria; in the hydrochlorothiazide group one had normoalbuminuria, three low microalbuminuria, and six high microalbuminuria (chi 2 test = 6.7; p = 0.03). Mean arterial pressure did not differ before (98 (SD 7) with enalapril v 97 (9) mm Hg with hydrochlorothiazide) or during treatment (88 (7) with enalapril v 90 (7) mm Hg with hydrochlorothiazide (analysis of variance, p = 0.5263)). Glomerular filtration rate did not vary. The aldosterone to active renin ratio was decreased by angiotensin I converting enzyme inhibition and increased by sodium depletion, showing treatment efficacy. CONCLUSION: Angiotensin I converting enzyme inhibition by enalapril effectively reduces microalbuminuria in normotensive diabetic patients whereas hydrochlorothiazide is not effective. Changes in blood pressure and activity of the renin-angiotensin-aldosterone system may contribute to these different effects. PMID- 8443482 TI - Prevalence of toxoplasma IgG among pregnant women in west London according to country of birth and ethnic group. PMID- 8443483 TI - Haemolytic uraemic syndrome during treatment with ketorolac trometamol. PMID- 8443484 TI - Syndrome of inappropriate secretion of antidiuretic hormone induced by diclofenac. PMID- 8443485 TI - Use of mobile screening unit for diabetic retinopathy in rural and urban areas. AB - OBJECTIVES: To compare the effectiveness of a mobile screening unit with a non mydriatic polaroid camera in detecting diabetic retinopathy in rural and urban areas. To estimate the cost of the service. DESIGN: Prospective data collection over two years of screening for diabetic retinopathy throughout Tayside. SETTING: Tayside region, population 390,000, area 7770 km2. SUBJECTS: 961 patients in rural areas and 1225 in urban areas who presented for screening. MAIN OUTCOME MEASURES: Presence of diabetic retinopathy, need for laser photocoagulation, age, duration of diabetes, and diabetic treatment. RESULTS: Compared with diabetic patients in urban areas, those in rural areas were less likely to attend a hospital based diabetic clinic (46% (442) v 86% (1054), p < 0.001); less likely to be receiving insulin (260 (27%) v 416 (34%), p < 0.001 and also after correction for differences in age distribution); more likely to have advanced (maculopathy or proliferative retinopathy) diabetic retinopathy (13% (122) v 7% (89), p < 0.001); and more likely to require urgent laser photocoagulation for previously unrecognised retinopathy (1.4% (13) v 0.5% (6), p < 0.02). The screening programme cost 10 pounds per patient screened and 1000 pounds per patient requiring laser treatment. CONCLUSION: The mobile diabetic eye screening programme detected a greater prevalence of advanced retinopathy in diabetic patients living in rural areas. Patients in rural areas were also more likely to need urgent laser photocoagulation. Present screening procedures seem to be less effective in rural areas and rural patients may benefit more from mobile screening units than urban patients. PMID- 8443486 TI - Developing a research and development strategy for primary care. AB - General practice research has been a minority activity and underfunded in the past. The creation of the purchaser and provider split, the introduction of medical audit, and the new research and development strategy for the NHS provide an opportunity to focus research on the health needs of the population. FHSAs, with the regional health authority, should develop a local strategy for research and development and appoint a lead officer, who may be the medical adviser. When negotiating contracts FHSAs need to back up their arguments with research evidence. NHS development research should cover quality, distribution, accessibility, outcome, and effectiveness. FHSAs should play a part in disseminating knowledge in the interests of achieving an effective and high quality service. GPs should be encouraged to participate in research by relaxing the regulations of compulsory hours of patient service and by creating a practice development allowance. PMID- 8443487 TI - Is the death rate from asthma exaggerated? Evidence from west Cumbria. AB - Although the death rate from asthma in England and Wales is reported to be about 2000 a year, clinical experience suggests that it is much rarer. Doctors in West Cumbria health district could recall only seven cases in 14 years. Examination of case notes of patients officially recorded as dying of asthma showed that many were aged over 60 and cigarette smokers. An alternative cause of death was evident in over half the patients. If the picture is representative of that in the whole of Britain the reported mortality from asthma may be much too high. PMID- 8443488 TI - Education and training of preregistration house officers: the consultants' viewpoint. AB - OBJECTIVE: To determine the opinions, attitudes, and requirements of consultants responsible for preregistration house officers in the light of the General Medical Council's Recommendations on General Clinical Training. DESIGN: A questionnaire was piloted asking 28 questions under the headings professional details, present training arrangements, effectiveness of current training, and perceived help required for implementing the recommendations. SETTING: Two teaching hospitals and nine district general hospitals in the Yorkshire region. SUBJECTS: 33 consultants (19 physicians, 14 surgeons) responded to an hour long interview. RESULTS: The traditional teaching ward round, with clinical meetings, was the main educational provision for house officers. Under a quarter of respondents provided specific teaching, which rarely exceeded 30 minutes weekly. Many delegated teaching to other junior or non-medical staff. Few consultants assessed the effectiveness of teaching, and feedback to juniors was rudimentary. There was strong support for the apprenticeship system and concern that it should not be downgraded. Appointing educational supervisors and introducing a structured educational programme were approved theoretically. Pressure on consultants to work faster, participate in audit and management, and accept financial responsibility for their clinical work, coupled with the reduction in junior doctors' hours, were considered to militate against educational developments. Many respondents felt frustrated and powerless. They would welcome an increased educational role but considered there must be conceptual, contractual, and financial changes. CONCLUSIONS: Fundamental changes are required by both consultants and management before the preregistration year can have proper educational value. Training in educational methods for consultants and a structured curriculum and formative assessment for trainees require recognition and financial support. PMID- 8443489 TI - The preregistration year. PMID- 8443490 TI - Other cities, same problems. AB - London's health care problems, particularly underfunding, are mirrored in other major cities in the United Kingdom and abroad. None has found the perfect solution, but the debates on the Tomlinson report provide an opportunity to review how to manage the three major areas of service provision, medical education, and research in London. Mr Robert Maxwell suggests that some aspects of the successful ambulatory care initiative in New York could be adapted by the capital's primary care providers while the secondary services might learn from the rationalisation of specialist services in Paris. PMID- 8443491 TI - Gangliosides and neurological diseases. PMID- 8443492 TI - Gangliosides and neurological diseases. PMID- 8443493 TI - Venous leg ulcers. PMID- 8443494 TI - Venous leg ulcers. PMID- 8443495 TI - Venous leg ulcers. PMID- 8443496 TI - Communicable disease control in London. PMID- 8443497 TI - Fundholding practices get preference. PMID- 8443498 TI - Tomlinson report. PMID- 8443499 TI - Fundholding practices get preference. PMID- 8443500 TI - American view of NHS reforms. PMID- 8443501 TI - Antithrombotic treatment and atrial fibrillation. PMID- 8443502 TI - Antithrombotic treatment and atrial fibrillation. PMID- 8443503 TI - White coat hyperglycaemia. PMID- 8443504 TI - Nurse triage. PMID- 8443505 TI - White coat hyperglycaemia. PMID- 8443506 TI - Nurse triage. PMID- 8443508 TI - Whistle blowing. PMID- 8443507 TI - Screening, ethics, and the law. PMID- 8443509 TI - Whistle blowing. PMID- 8443510 TI - Managing urinary tract infection. PMID- 8443511 TI - Social class differences in infant mortality. PMID- 8443512 TI - Natural remedies. PMID- 8443513 TI - Sexual behavior. PMID- 8443514 TI - Sexual behavior. PMID- 8443515 TI - Tuberculosis in Britain today. PMID- 8443516 TI - BCG vaccination against tuberculosis: international perspectives. PMID- 8443517 TI - The laryngeal mask. PMID- 8443518 TI - Diagnostic dilatation and curettage in young women. PMID- 8443519 TI - Assessing hospital technology in The Netherlands. PMID- 8443520 TI - Risk factors for development of flucloxacillin associated jaundice. AB - OBJECTIVES: To identify risk factors predisposing to the development of flucloxacillin associated jaundice. DESIGN: Case-control study. Medical records of cases and controls were reviewed and information recorded on standard data collection forms. SETTING: Alfred Hospital recruiting subjects from Melbourne, Sydney, and Brisbane. SUBJECTS: Cases were defined as patients who had developed jaundice within eight weeks of stopping flucloxacillin, biochemical test results suggesting cholestasis, normal calibre bile ducts, and not been taking recognised hepatotoxic drugs. 51 of the 53 patients referred were included in the study. Four controls for each case were randomly selected from the patient register of the prescribing doctor. These were defined as patients who had been prescribed flucloxacillin without developing jaundice. MAIN OUTCOME MEASURES: Demographic characteristics, medical history, indication for flucloxacillin, dose, route and duration of treatment, other drugs, smoking, and previous drug allergies or use of flucloxacillin. RESULTS: Increasing age and a prolonged duration of flucloxacillin treatment were found to be risk factors for the development of jaundice. Patients aged over 55 years had an odds ratio of 18.61 (95% confidence interval 5.16-67.17) compared with patients under 30. The odds ratio for patients prescribed flucloxacillin for over 14 days was 7.13 (2.90 to 17.58) compared with patients treated for 14 days or less. Dose and route of administration were not related to the risk of jaundice. CONCLUSIONS: Older patients and those receiving flucloxacillin for longer than two weeks are at a substantially greater risk of jaundice. Careful consideration of the risk-benefit ratio is required when flucloxacillin is used in these settings. PMID- 8443521 TI - Diagnostic dilatation and curettage: is it used appropriately? AB - OBJECTIVE: To determine patterns of use of dilatation and curettage in Britain as compared with those in the United States; to examine variations in utilisation rates within one regional health authority. DESIGN: Analysis of routinely collected hospital inpatient statistics. SETTING: Statistics for England, Scotland, and the United States; local statistics for Oxford region. SUBJECTS: All inpatient episodes in which dilatation and curettage was performed but excluding those related to pregnancy. RESULTS: Dilatation and curettage rates remained stable in Britain between 1977 and 1990, whereas in the United States they declined dramatically. In 1989-90 the rate was 71.1 per 10,000 women in England as compared with only 10.8 per 10,000 in America. In 1989, 6936 women underwent diagnostic dilatation and curettage in the Oxford region, making it the most common elective operation. A total of 2726 (39%) of these women were under 40. There was a more than twofold variation in usage of the procedure among district health authorities within the region and even greater variation in rates in women under 40. The proportion of patients treated as day cases in the district general hospitals ranged from 22% to 82%. CONCLUSIONS: Dilatation and curettage may frequently be used inappropriately. The considerable variations in usage of dilatation and curettage internationally and nationally indicate differences in clinical perception of its appropriateness. This makes it suitable for audit. In developing guidelines it will be important to agree on the most appropriate patients and the relative merits of alternative methods of endometrial sampling. Probably this could result in considerable cost savings at no risk and possibly some benefit to patients. PMID- 8443522 TI - Microalbuminuria: associations with height and sex in non-diabetic subjects. AB - OBJECTIVES: To study the association(s) between microalbuminuria and cardiovascular risk factors in non-diabetic subjects. DESIGN: Patients aged 40-75 years were randomly selected from a general practice list and invited to participate. SETTING: Health centre in inner city London. SUBJECTS: Of those invited, 1046 out of 1671 (62.6%) attended. Subjects were excluded for the following reasons: not being white (44); urinary albumin excretion rate > 200 micrograms/min (3); having a urinary infection (5); taking penicillamine or angiotensin converting enzyme inhibitors (7); older than 75 (2); having diabetes (25); missing data on glucose concentration (1). MAIN OUTCOME MEASURES: Glucose tolerance test results, albumin excretion rate from overnight and timed morning collections of urine; blood pressure; height. RESULTS: Mean albumin excretion rate was significantly lower in women than men (mean ratio 0.8, 95% confidence interval (0.69 to 0.91)). Mean albumin excretion rate was significantly associated with age, blood pressure, and blood glucose concentration (fasting, 1 hour, and 2 hour) in men and inversely with height. Men who had microalbuminuria in both samples were significantly shorter (by 5 cm (1.3 to 9.3 cm)) than those who had no microalbuminuria in either sample when age was taken into account. In the case of women only systolic pressure was significantly associated with albumin excretion rate. CONCLUSIONS: Microalbuminuria and short stature in men are associated. Cardiovascular risk has been associated with both of these factors and with lower birth weight. The inverse association of microalbuminuria with height is compatible with the suggestion that factors operating in utero or early childhood are implicated in cardiovascular disease. The higher prevalence of microalbuminuria in men compared with women may indicate that sex differences in cardiovascular risk are reflected in differences in albumin excretion rate. PMID- 8443523 TI - Low systolic blood pressure and self perceived wellbeing in middle aged men. AB - OBJECTIVE: To examine the relation between systolic blood pressure and self perceived wellbeing in 50 year old men. DESIGN: Cross sectional population study of data derived from questionnaires and physical examination as a part of a cardiovascular risk factor survey. SETTING: City of Gothenburg, Sweden. STUDY POPULATION: 776 men from a random population sample of 1016 men aged 50. METHODS: Self perceived wellbeing according to the Gothenburg quality of life questionnaire, which is an assessment of social, physical, and mental wellbeing in 15 different areas. MAIN RESULTS: Low systolic blood pressure was significantly (p < 0.05) related to impaired social wellbeing in four areas: work, home and family, financial situation, and housing. Of the items dealing with physical wellbeing, health, memory, and appetite were significantly related to blood pressure. As regards mental wellbeing, energy and self confidence were significantly related to systolic blood pressure. Diastolic blood pressure was significantly related to housing, memory, energy, patience, and self confidence. In multiple regression analyses that controlled for smoking, stress, physical activity, social activity, and emotional support, poor social, physical, and mental wellbeing were all significantly related to low systolic blood pressure independently of other factors. Low diastolic blood pressure was independently associated with poor physical and mental, but not social, wellbeing. CONCLUSION: Low systolic blood pressure was associated with poor perception of wellbeing in several areas. The cause is unclear. PMID- 8443524 TI - Hepatitis associated with terbinafine treatment. PMID- 8443525 TI - Serotonin syndrome caused by a moclobemide-clomipramine interaction. PMID- 8443526 TI - Vaccine related glomerulonephritis. PMID- 8443528 TI - Commissioning for quality. PMID- 8443527 TI - Death from cancer at home: the carers' perspective. AB - OBJECTIVES: To collect information from principal carers of people who had died at home with cancer; to identify areas of support which need improvement. DESIGN: Semistructured interviews with carers two to four months after the death. SETTING: 38 general practices in the Exeter, Torbay, and Plymouth health districts. SUBJECTS: 207 carers. MAIN OUTCOME MEASURES: Services received by carers and quality of support. RESULTS: 161 of 207 patients were aged 60 or over. 88 carers were aged under 60, 110 were 60-80, and 9 were > 80. Carers had difficulty in getting urgent professional help in only 15 out of 177 cases. 124 carers were not given advice on financial help and 174 were not told of support available from local charities. Although pain was well controlled, 25% of patients had no relief of other symptoms. Overall, 150 carers considered the support excellent, 45 good, 8 moderate, 2 poor, and 2 had no comment. CONCLUSIONS: Although care has improved in recent years, health professionals need to give carers more advice about help available outside health services. Domestic help was often needed earlier. Better appreciation of carers' problems is needed. PMID- 8443529 TI - The dangers of libel and how to avoid them. PMID- 8443530 TI - Trends in health care and their effects on medical education. PMID- 8443531 TI - Making progress--community care in Northern Ireland. PMID- 8443532 TI - Obstetric complications and schizophrenia. PMID- 8443533 TI - Obstetric complications and schizophrenia. PMID- 8443534 TI - Obstetric complications and schizophrenia. PMID- 8443535 TI - Obstetric complications and schizophrenia. PMID- 8443536 TI - Monitoring lithium treatment. PMID- 8443537 TI - Monitoring lithium treatment. PMID- 8443538 TI - Postmenopausal hormone replacement therapy. PMID- 8443539 TI - Postmenopausal hormone replacement therapy. PMID- 8443540 TI - Poor growth in children. PMID- 8443541 TI - Poor growth in children. PMID- 8443542 TI - Predictive value of microalbuminuria in longstanding insulin dependent diabetes. PMID- 8443543 TI - Predictive value of microalbuminuria in longstanding insulin dependent diabetes. PMID- 8443544 TI - Predictive value of microalbuminuria in longstanding insulin dependent diabetes. PMID- 8443545 TI - Informing patients about clinical trials. PMID- 8443546 TI - Managing depression in general practice. PMID- 8443547 TI - The health divide. PMID- 8443548 TI - Consultant episodes. PMID- 8443549 TI - Posttraumatic tibial osteomyelitis: diagnosis, classification, and treatment. AB - The problem of osteomyelitis has, to date, not been completely resolved. Recent research has provided additional insight into the pathogenesis of bone infection. Advances in pharmacology and in surgical techniques have enhanced our ability to treat such infections. Despite these advances, successful treatment of posttraumatic tibial osteomyelitis depends on adherence to several basic principles: complete debridement of necrotic and infected tissue, obtaining bony stability, the elimination of dead space, and the provision of durable soft tissue coverage. Armed with this new knowledge and surgical ability, treatment results have improved. We do not know, however, whether osteomyelitis can ever be "cured," since infections become manifest many years after injury or treatment. PMID- 8443550 TI - Intramedullary nailing of subtrochanteric fractures: a critical review of device failure and case analysis. AB - Although device failure in intramedullary (IM) nailing of subtrochanteric fractures is uncommon, breakage of the nail can occur. Following a review of the literature on this subject, a case is reported that illustrates the surgical and biomechanical factors that can lead to nail failure. PMID- 8443551 TI - Glenohumeral arthroplasty: a critical review of indications and preoperative considerations. AB - Total shoulder arthroplasty has become an effective treatment for advanced glenohumeral arthritis. The results depend, in part, on the underlying degenerative process. This article reviews the indications for glenohumeral arthroplasty, including important preoperative considerations. The different types of glenohumeral arthritides are discussed with respect to their clinical and radiographic manifestations, as well as their impact on preoperative planning. PMID- 8443552 TI - Residency in 1933: a view from afar. PMID- 8443553 TI - Neuropathy of the saphenous nerve as a cause of knee pain. AB - Neuropathy of the infrapatellar branch of the saphenous nerve is a frequently overlooked cause of persistent medical knee pain. The author wishes to identify this as a distinct entity and to present five cases. All of these cases were caused by direct blows to the medial aspect of the knee, did not respond to conservative treatment, and were essentially cured via neurolysis or neurectomy of the infrapatellar branch. Nerve entrapment is a frequent cause of intractable symptomatology in various areas of the body. The most commonly recognized nerve entrapment condition is carpal tunnel syndrome. Another condition, saphenous nerve entrapment, is all too frequently overlooked and underdiagnosed. PMID- 8443555 TI - Skeletal fixation: a review. AB - While improvements in surgical techniques and recent trends toward early surgery and patient mobilization have led to skeletal traction being utilized more sparingly, it continues to be a basic skill required by the orthopaedic surgeon. The most commonly used anatomical sites for skeletal fixation--distal femur, proximal tibia, distal tibia, calcaneus, and olecranon--are reviewed and illustrated. PMID- 8443554 TI - Trispiral tomography and magnetic resonance imaging of the wrist. AB - Tomography, which permits a far more accurate visualization of lesions than conventional radiographs, is conducted via several different methods, depending on the specific movement of the x-ray tube. Linear tomography is the simplest method but produces images that appear streaked. Zonotomography, which uses an elliptical or figure-8 movement of the x-ray tube, creates a uniform blurring of structures and a much clearer resolution of the plane of focus. Even sharper images are produced by multidirectional trispiral tomography, which is described as well as its application to specific anatomic areas of the wrist. The normal anatomy and a variety of problems of the wrist as visualized with magnetic resonance imaging are also described. PMID- 8443556 TI - Synovial copper deposition as a possible explanation of arthropathy in Wilson's disease. AB - A patient with longstanding Wilson's disease and arthritis is presented. Synovial biopsy disclosed thickening of the membrane, intimal histiocytes, and lymphocyte infiltration without pigmentation. X-ray energy spectroscopy demonstrated copper and iron in high concentrations. These findings may contribute to our understanding of the development of the arthropathy in patients with Wilson's disease. PMID- 8443557 TI - Avascular necrosis of the femoral head following intertrochanteric fracture. AB - Two cases are reported of avascular necrosis of the femoral head occurring as a late complication of an intertrochanteric fracture. The cases are presented to emphasize the importance of including this condition in the differential diagnosis of any late clinical deterioration following such an injury. PMID- 8443558 TI - Symptomatic displacement of the lesser trochanter following trochanteric fracture fixation. AB - Unstable intertrochanteric hip fractures are characterized by comminution of the posteromedial cortex, resulting in a fragment of variable size containing the lesser trochanter. Controversy exists as to whether it is necessary to perform reduction and fixation of this fragment. This case lends further support to the practice of fixating the lesser trochanteric fragment in unstable intertrochanteric fractures. PMID- 8443559 TI - Scapular osteochondroma presenting with exostosis bursata. AB - A 33-year-old male presented with acute onset of scapular winging following an injury to the shoulder girdle. A scapular osteochondroma was identified radiographically that was completely asymptomatic until the time of injury. Clinical presentation included the presence of a large exostosis bursata. Surgical resection of the osteochondroma resulted in resolution of all signs and symptoms. PMID- 8443560 TI - Intraosseous ganglion of the lunate. PMID- 8443561 TI - Eosinophilic granuloma of the left ischium. AB - A case of eosinophilic granuloma in an unusual location (ischium) is presented. Eosinophilic granuloma, a benign lesion of bone, has many radiographic appearances that vary with location. The flat bone of the skull and pelvis are common sites of involvement. Although the iliac wings and pubic rami are not uncommon sites for such a lesion, the ischium is a rare site. This occurrence prompted us to report this case. PMID- 8443562 TI - Repair of peripheral nerve defects by controlled distraction: a preliminary study. AB - Five cats underwent a 3.0-cm removal of their ulnar nerves followed by delayed repair. One limb received a standard cable grafting procedure, and the other side had the proximal nerve stump lengthened by controlled distraction and a subsequent direct anastomosis. Histological examination of the lengthened nerves revealed better quality than the grafted nerves in all cats. Nerve conduction velocity of the lengthened side was greater than the graft side in three cats. It appears that this technique of nerve lengthening and direct repair might have clinical applicability. PMID- 8443563 TI - The cellular and physiological actions of insulin in the central nervous system. AB - Insulin is a peptide hormone involved in the regulation of glucose homeostasis. Its synthesis and function in the peripheral tissues have been extensively studied and well understood. In contrast, demonstration of insulin in the brain has raised questions concerning its origin and physiological significance. In spite of extensive studies, the source of insulin present in the brain has not yet been conclusively identified. Evidence exists in support of both peripheral and central origins of this hormone in the brain. Recognized physiological effects of insulin in the central nervous system (CNS) include regulation of food intake, control of glucose uptake and trophic actions on neuronal and glial cells. These actions of insulin are mediated by insulin receptor resembling closely that in peripheral tissues and coupled with tyrosine kinase signal transduction pathway. In this review we will discuss theories concerning the origin of insulin in the CNS. In addition, we will present current information on both cellular and physiological effects of this hormone in the brain. PMID- 8443564 TI - Levels of ethanolamine intermediates in the human and rat visual system structures: comparison with neural tissues of a lower vertebrate (Mustelus canis) and an invertebrate (Loligo pealei). AB - Levels of ethanolamine intermediates in the retina and optic nerves of autopsied human donors and in the rat visual system (retina, optic nerve, lateral geniculate body, superior colliculus) were measured. Amounts were also obtained from the retina, optic nerve, and optic tectum of a primitive elasmobranch, the smooth dogfish Mustelus canis, and from the related nervous structures (retina, optic lobe, fin nerve, and stellate ganglia) of a marine invertebrate, the squid Loligo pealei. In all regions of the human and rat nervous system, the pool size of CDP-ethanolamine (values ranging between 10-31 nmol/g wet wt) was much smaller than that of free ethanolamine (values ranging between 197-395 nmol/g wet wt), whereas glycerophosphorylethanolamine was present in relatively high content (values ranging between 125-280 nmol/g wet wt). In nervous system regions of the dogfish and squid, the distribution of values followed the same general trend as observed for humans and rats, even if all regions had less ethanolamine intermediates compared to the mammalian counterpart. In dogfish and squid retina, glycerophosphorylethanolamine showed the highest pool size among the ethanolamine derivatives analyzed (16 and 44 nmol/g wet wt, respectively). The present study confirms the basic similarity of ethanolamine intermediate pool size patterns in the nervous system structures (with the exception of the retina) of animal species which have widely different phylogenetic positions. The data support the proposal that the levels reached by ethanolamine and its derivatives in the nervous tissue is the result of an ancient evolutionary development of metabolic pathways for the maintenance of phosphatidylethanolamine membraneous content. PMID- 8443565 TI - Dipeptidyl peptidase I from goat brain: purification, characterization and its action on Leu-enkephalin. AB - Brain dipeptidyl peptidase (DPP) I has been purified 2990-fold to apparent homogeneity shown by a single protein band in electrophoreses at pH 4.5, 8.4 and in SDS-PAGE at pH 7.2. The purification techniques included homogenization of brain acetone powder, autolysis at pH 4.2, 30-80% (NH4)2SO4 fractionation. Sephadex G-100 column chromatography, heat treatment at 65 C. organomercurial affinity chromatography. CM-Sephadex cation-exchange chromatographies at pH 5.6 and 5.0 and anion-exchange chromatography on DEAE-Sephadex at pH 6.8. The enzyme hydrolysed synthetic substrate Gly-Arg-4-methoxy-beta-naphthyl-amide maximally at pH 6.0. The Km values for Gly-Arg-beta-naphthylamide and Gly-Arg-4-methoxy-beta naphthylamide substrates were 0.10 mM and 0.14 mM respectively. The enzyme was inhibited by thiol inhibitors like p-chloromercuribenzoic acid, iodoacetic acid, iodoacetamide and microbial inhibitors leupeptin and antipain. Molecular weight estimations on a calibrated Sephadex G-200 column afforded a value of 180,000 Da while in denaturing conditions on sodium dodecyl sulphate polyacrylamide gel electrophoresis, the subunit molecular weight was 22,000 Da. The subunit structure of the native enzyme was unfolded in presence of different concentrations of urea. In 8 M urea, the enzyme dissociated completely into monomers of 25,000 Da but 6, 5 and 4 M urea concentrations revealed the existence of dimers, tetramers and hexamers. Leu-enkephalin. Tyr-Gly-Gly-Phe-Leu was degraded by DPPI into Tyr-Gly and Gly-Phe-Leu with no further degradation of the newly generated tripeptide. PMID- 8443566 TI - Effects of chlorpromazine on phosphatidylserine biosynthesis in rat pup brain exposed to ethanol in utero. AB - Phosphatidylserine biosynthesis in rat pup brain was examined by assaying the serine base-exchange enzyme activity in the microsomal and plasma membrane fractions, and by measuring the incorporation of [3H]serine into phosphatidylserine in brain slices and in the intact brain. Chlorpromazine, either added in vitro into the incubation system or administered to animals via i.p. injection or feeding a liquid diet, gave rise to an increase in the phosphatidylserine biosynthesis activity. Ethanol administered in the form of a liquid diet to pregnant rats (day 11 birth) resulted in a decrease in phosphatidylserine biosynthesis in the newborn and developing brain. The ethanol induced decrease in phosphatidylserine biosynthetic activity could be reversed by adding chlorpromazine to the ethanol diet. Results demonstrate that phosphatidylserine biosynthesis in the neonatal brain is affected in opposite directions by chlorpromazine and ethanol. This poses the possibility that chlorpromazine administration may be effective in alleviating the deleterious effects caused by the decreased phosphatidylserine biosynthesis in brain due to in utero ethanol exposure. PMID- 8443567 TI - Regional binding of 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP) to muscarinic receptors in rat brain and comparative analysis of minimum energy conformations. AB - The binding of the muscarinic antagonist 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP), which has been suggested as an M3-selective antagonist in peripheral tissues, was examined through quantitative autoradiographic techniques in brain. The ability of 4-DAMP to displace [3H](R)-quinuclindinyl benzilate (QNB) binding to rat brain sections was compared with the known distribution of M1 and M2 muscarinic receptor subtypes as measured previously with pirenzepine and AF-DX 116 (Messer et al., 1989a). 4-DAMP displayed a high affinity for [3H](R)-QNB binding sites in rat brain sections. Analysis of 4-DAMP binding to various brain regions revealed heterogeneous binding profiles, suggesting an interaction with multiple receptor sites. Quantification of the autoradiograms indicated that 4-DAMP bound with the highest affinity to muscarinic receptors in the midline thalamus (IC50 values < 30 nM), and had a slightly lower affinity for hippocampal receptors (IC50 values between 30 and 46 nM). 4-DAMP also displayed a lower affinity for cortical receptors with IC50 values between 30 and 50 nM. The binding profile of the putative M3 muscarinic antagonist did not exhibit a marked selectivity for any single region of brain. The data suggest that whereas 4-DAMP may be selective for M3 receptors in peripheral tissues, it has limited selectivity in the CNS. Minimum energy conformations for 4-DAMP were calculated using molecular mechanics calculations. 4-DAMP displayed two global minimum energy conformations, differing in the relative position of the piperidine ring with respect to the aromatic rings. The minimum energy conformations of 4-DAMP were compared with conformations generated for pirenzepine (Messer et al., 1989a). The lowest energy conformation of 4-DAMP was superimposable on the lowest energy conformation of pirenzepine (RMS = 0.297 A). It is suggested that the conformations available to 4-DAMP permit binding to several muscarinic receptors in the CNS. PMID- 8443568 TI - The thiobarbituric acid assay reflects susceptibility to oxygen induced lipid peroxidation in vitro rather than levels of lipid hydroperoxides in vivo: a methodological approach. AB - Although the hypothesis of oxidative stress as a pathogenetic factor of neurodegenerative diseases became a matter of interest recently, direct evidence supporting this hypothesis is rare. The most prominent assay being currently used as an index for lipid peroxidation products in vivo is the thiobarbituric acid assay. Thiobarbituric acid reactive substances are mainly formed during the decomposition of lipid hydroperoxides in vitro. It is questionable however, that all species detectable with thiobarbituric acid are derived from in vivo preformed lipid hydroperoxides. These studies were undertaken to investigate the influence of autoxidation reactions on colour production during the acid heating stage of the assay. If driven aerobically, more than 90% of thiobarbituric acid reactive substances are newly generated in vitro during incubation at 95 degrees C for 75 min. This process can be enhanced by addition of ferric iron. Chain breaking antioxidants like butylated hydroxytoluene decrease colour formation in the absence or in the presence of iron. If driven anaerobically under argon, colour formation was only 10% of aerobically heated homogenates or lipid extracts of human brain tissue. These results may indicate that measurement of thiobarbituric acid reactive substances under the aerobic conditions described here reflects to a great extent the susceptibility of brain tissue or lipids to oxygen-induced formation of lipid hydroperoxides in vitro rather than degradation products of in vivo performed lipid hydroperoxides. PMID- 8443569 TI - GABA transporter mRNA: in vitro expression and quantitation in neonatal rat and postmortem human brain. AB - A previously isolated rat cDNA clone encoding the membrane transporter for the neurotransmitter gamma-aminobutyric acid was expressed in transfected COS cells. The resultant transporter protein was characterized kinetically and pharmacologically. The apparent Kt (6.1 microM) and the pharmacological profile of a neuronal-type transporter observed in these mammalian cells were consistent with previous data obtained in Xenopus laevis oocytes. Post-natal levels of gamma aminobutyric acid transporter mRNA in rat cerebellum, cerebral cortex and striatum (as measured by nuclease protection assay) transiently exceeded levels present in the adult brain. Human gamma-aminobutyric acid transporter mRNA also was measured by nuclease protection assay using as probe a human transporter cDNA homolog obtained by polymerase chain reaction. These studies suggest that quantitation of rat and human gamma-aminobutyric acid transporter mRNAs may provide a useful index of transporter gene expression. PMID- 8443570 TI - Free choline and choline metabolites in rat brain and body fluids: sensitive determination and implications for choline supply to the brain. AB - In the central nervous system, choline is an essential precursor of choline containing phospholipids in neurons and glial cells and of acetylcholine in cholinergic neurons. In order to study choline transport and metabolism in the brain, we developed a comprehensive methodical procedure for the analysis of choline and its major metabolites which involves a separation step, selective hydrolysis and subsequent determination of free choline by HPLC and electrochemical detection. In the present paper, we report the levels of choline, acetylcholine, phosphocholine, glycerophosphocholine and choline-containing phospholipids in brain tissue, cerebrospinal fluid and blood plasma of the untreated rat. The levels of free choline in blood plasma (11.4 microM), CSF (6.7 microM) and brain intracellular space (64.0 microM) were sufficiently similar to be compatible with an exchange of choline between these compartments. In contrast, the intracellular levels of glycerophosphocholine (1.15 mM) and phosphocholine (0.59 mM) in the brain were considerably higher than their CSF concentrations of 2.83 and 1.70 microM, respectively. In blood plasma, glycerophosphocholine was present in a concentration of 4.58 microM while phosphocholine levels were very low or absent (< 0.1 microM). The levels of phosphatidylcholine and lyso-phosphatidylcholine were high in blood plasma (1267 and 268 microM) but very low in cerebrospinal fluid (< 10 microM). We concluded that the transport of free choline is the only likely mechanism which contributes to the supply of choline to the brain under physiological conditions. PMID- 8443571 TI - Cholinergic lesions of mouse striatum induced by AF64A alter D2 dopaminergic behavior and reduce D2 dopamine receptors and D2 dopamine receptor mRNA. AB - To determine whether dopamine receptors are expressed in acetylcholine-containing neurons intrinsic to the striatum, and to study further the interactions between the dopaminergic and cholinergic systems, the irreversibly acting cholinergic neurotoxin, ethylcholine mustard aziridinium ion (AF64A), was injected unilaterally into the mouse corpus striatum, and rotational behavior induced by dopamine agonists and certain molecular events associated with this lesion were determined 7 days after lesioning. Brains were analyzed for D2 dopamine receptors by autoradiography, using [3H](-)sulpiride as a ligand, and for D2 dopamine receptor mRNA and glutamic acid decarboxylase mRNA by Northern blot analysis, using selective radiolabelled oligonucleotide probes. Choline uptake sites were determined by binding assays using [3H]hemicholinium-3, a selective choline reuptake blocker, as a ligand. Mice with intrastriatal injections of AF64A showed ipsilateral rotational responses to the non-selective dopamine agonist apomorphine and to the D2 dopamine agonists, pergolide and quinpirole, but not to the D1 dopamine agonist SKF 38393. This was associated with a significant reduction in D2 dopamine receptors in the ipsilateral striatum and a significant decrease in the amount of D2 dopamine receptor mRNA. That AF64A produced a relatively selective cholinergic deficit was supported by the evidence showing that AF64A lesions significantly reduced [3H]hemicholinium-3 binding sites but did not alter glutamic acid decarboxylase (GAD) mRNA. Further, hemicholinium-3, prevented the AF64A-induced changes in rotational behavior. These results suggest that striatal cholinergic interneurons contain D2 dopamine receptors and express the D2 dopamine receptor gene, and that these interneurons are involved in dopamine-mediated rotational behavior. PMID- 8443572 TI - Mutagenic oligonucleotide-directed PCR amplification (Mod-PCR): an efficient method for generating random base substitution mutations in a DNA sequence element. AB - Saturation mutagenesis is one approach for determining the contributions of individual base pairs to the structure and function of defined DNA sequence elements. In this paper, we describe a novel method for saturation mutagenesis involving PCR amplification with degenerate synthetic oligonucleotides as primers. The degeneracy is confined to a specific target within the primer by mixing a low percentage of the three non-wild type (non-WT) nucleotide precursors with WT at specific positions during primer synthesis. PCR amplification of WT template DNA with the degenerate primer and an opposing WT primer, followed by subsequent cloning using restriction sites designed into the primers, results in recovery of a population of randomly mutated products. Since primers with multiple mutations hybridize less efficiently to WT template DNA during PCR amplification, the recovery of mutants with multiple base changes is greatly reduced. The efficient generation of random point mutations with this method allows the construction of separate mutant populations, each mutagenized over a different portion of the DNA sequence element. If a phenotypic assay is available, these populations can be screened directly to define those regions within the element that are important for activity. Only those populations containing mutations in the important regions require further characterization by DNA sequence analysis. PMID- 8443573 TI - PCR amplification of SRY-related gene sequences reveals evolutionary conservation of the SRY-box motif. AB - SRY (sex-determining region of the Y chromosome) has recently been identified as a key regulatory gene in mammalian sex determination. The open reading frame of this gene contains an 80-amino-acid motif, the SRY-box, which shares a high degree of homology with a DNA-binding domain found in the high-mobility-group (HMG) proteins HMG1 and HMG2. The SRY box motif is highly conserved in several sequence-specific DNA-binding proteins that are known to act as transcription factors. Here we describe the use of degenerate PCR primers to identify SRY related sequences containing the SRY-box motif from the genomic DNA of a variety of species. The results of this study suggest that in a diverse array of species SRY-related genes may serve as transcription factors that regulate a variety of developmental pathways, including sex determination. PMID- 8443574 TI - Synthesis and characterization of 5'-fluorescent-dye-labeled oligonucleotides. AB - Fluorescent-dye-labeled oligonucleotides are used in many procedures, including DNA sequencing, PCR, restriction mapping, the study of genetic disease, and forensics identification. In this paper, we describe detailed methods for the synthesis, purification, and quantification of 5'-fluorescent-dye-labeled oligonucleotides. The relationship of specific and nonspecific dye attachment to synthetic oligonucleotides is discussed, and the importance of primer design is considered as a way to prevent chemical problems from interfering with biological reactions. PMID- 8443575 TI - Partial endonuclease digestion mapping of restriction sites using PCR-amplified DNA. AB - Although direct DNA sequencing is now readily available, restriction enzyme analyses are still widely used in population genetics and molecular systematics studies. These analyses provide cheaper and faster ways to assay patterns of nucleotide differentiation across a large number of individuals. In this paper, we introduce a new approach to restriction enzyme analyses in which high resolution restriction site maps are obtained from partial digestions of PCR products. This procedure increases the level of resolution at least an order of magnitude over the double-digestion method for restriction enzyme mapping, can target specific DNA regions with the use of specific primers, and, because it uses chemiluminescent detection of DNA, can be easily implemented in laboratories that lack the necessary setups to handle radioactive substances. PMID- 8443576 TI - PCR buffer optimization with uniform temperature regimen to facilitate automation. AB - To facilitate PCR(1,2) reactions in large numbers with uniform conditions, the annealing temperature was fixed and the stringency of the reactions was adjusted by optimizing the ion conditions of the reaction. The buffer system is based primarily on Tris (T), ammonium (N), and potassium (K) to adapt assay conditions to different primer pairs. The TNK buffers have permitted successful screening of a 60,000-clone yeast artificial chromosome (YAC) library with more than 200 primer pairs. PMID- 8443577 TI - Sensitive two-stage PCR of p53 genomic DNA exons 5-9. AB - To assess the status of the tumor suppressor gene p53 from samples with low levels (sub-nanogram amounts) of genomic DNA (e.g., from exfoliated cells, skin, small biopsies, mucosa), a technique based on two successive rounds of PCR was developed. In the first round, a 1.84-kb fragment spanning exons 5-9 was generated using a "touchdown" protocol. After purification by spun-column chromatography, this fragment was used as a template for the amplification of the individual exons 5-9 with inner primer sets specific for the adjacent intronic regions. Using this nested primer approach, several micrograms of each individual exon were obtained starting from as little as 62.5 pg of total genomic DNA. This material proved ideal for future analyses by single-strand conformational polymorphism (SSCP) analysis and DNA sequencing. PMID- 8443578 TI - Unwanted mutations in PCR mutagenesis: avoiding the predictable. PMID- 8443579 TI - Differential detection of colinear genes and RNA transcripts by modified reverse transcription and PCR. PMID- 8443580 TI - Rapid preparation of limited biological samples for small-volume PCR. PMID- 8443581 TI - Effect of primer selection on spuriously generated deletion of a tandem repeat during PCR. PMID- 8443582 TI - Efficient total gene synthesis of 1.35-kb hybrid alpha-lytic protease gene using the polymerase chain reaction. PMID- 8443583 TI - Peptide-protein interaction markedly alters the functional properties of the catalytic subunit of aspartate transcarbamoylase. AB - Interaction of a 70-amino acid zinc-binding polypeptide from the regulatory chain of aspartate transcarbamoylase (ATCase) with the catalytic (C) subunit leads to dramatic changes in enzyme activity and affinity for ligand binding at the active sites. The complex between the polypeptide (zinc domain) and wild-type C trimer exhibits hyperbolic kinetics in contrast to the sigmoidal kinetics observed with the intact holoenzyme. Moreover, the Scatchard plot for binding N (phosphonacetyl)-L-aspartate (PALA) to the complex is linear with a Kd corresponding to that evaluated for the holoenzyme converted to the relaxed (R) state. Additional evidence that the binding of the zinc domain to the C trimer converts it to the R state was attained with a mutant form of ATCase in which Lys 164 in the catalytic chain is replaced by Glu. As shown previously (Newell, J.O. & Schachman, H.K., 1990, Biophys. Chem. 37, 183-196), this mutant holoenzyme, which exists in the R conformation even in the absence of active site ligands, has a 50-fold greater affinity for PALA than the free C subunit. Adding the zinc domain to the C trimer containing the Lys 164-->Glu substitution leads to a 50 fold enhancement in the affinity for the bisubstrate analog yielding a value of Kd equal to that for the holoenzyme. A different mutant ATCase containing the Gln 231 to Ile replacement was shown (Peterson, C.B., Burman, D.L., & Schachman, H.K., 1992, Biochemistry 31, 8508-8515) to be much less active as a holoenzyme than as the free C trimer. For this mutant holoenzyme, the addition of substrates does not cause its conversion to the R state. However, the addition of the zinc domain to the Gln 231-->Ile C trimer leads to a marked increase in enzyme activity, and PALA binding data indicate that the complex resembles the R state of the holoenzyme. This interaction leading to a more active conformation serves as a model of intergenic complementation in which peptide binding to a protein causes a conformational correction at a site remote from the interacting surfaces resulting in activation of the protein. This linkage was also demonstrated by difference spectroscopy using a chromophore covalently bound at the active site, which served as a spectral probe for a local conformational change. The binding of ligands at the active sites was shown also to lead to a strengthening of the interaction between the zinc domain and the C trimer. PMID- 8443584 TI - Control of nucleation in the crystallization of lysozyme. AB - This work investigates the influence of storage of lysozyme in solution on its crystallization. The crystallization of hen egg-white lysozyme exhibits a storage effect (aging) that depends on the length of time the lysozyme solution is stored, after dissolving from freeze-dried powder, before being brought to crystallization conditions. The number of crystals obtained increases, while their size decreases, as the solution ages. Observations suggest that this effect is due to the presence of fungi that multiply in the stored protein solution. This aging effect was used to control nucleation and determine the number and size of lysozyme crystals to be formed in a given sample. PMID- 8443585 TI - Probing the pyrophosphate-binding site in potato tuber UDP-glucose pyrophosphorylase with pyridoxal diphosphate. AB - Potato tuber UDP-glucose pyrophosphorylase (EC 2.7.7.9) catalyzes the reversible uridylyl transfer from UDP-glucose to MgPPi forming glucose 1-phosphate and MgUTP, according to an ordered bi-bi mechanism in which UDP-glucose and MgPPi bind in this order. To probe the active site of this enzyme, we have applied pyridoxal 5'-diphosphate, a reactive PPi analogue. The enzyme was rapidly inactivated when incubated with the reagent in the presence of Mg2+ followed by sodium borohydride reduction. The degree of the inactivation was decreased by MgUTP, MgPPi, and glucose 1-phosphate, but enhanced by UDP-glucose. The enhancement was prevented by co-addition of Pi, the competitive inhibitor with respect to PPi. The complete inactivation corresponded to the incorporation of 0.9-1.1 mol of reagent/mol of enzyme monomer. In the presence of UDP-glucose, labels were almost exclusively incorporated into Lys-329. Thus, this residue may be located near the bound MgPPi and its modification is promoted, probably through conformational changes, by the binding of UDP-glucose to the enzyme. The results of the modification by the same reagent of the mutant enzymes in which Lys-329 and Lys-263 are individually replaced by Gln suggest the roles of these lysyl residues in the binding of MgPPi and in the UDP-glucose-induced conformational changes, respectively. PMID- 8443586 TI - Pro to Gly (P219G) in a silent glycosylation site results in complete glycosylation in tissue plasminogen activator. PMID- 8443587 TI - Rapid, spontaneous reassembly of homo- and heterodimeric tropomyosin two-chain coiled coils from unfolded single alpha and beta chains. PMID- 8443588 TI - Zinc- and sequence-dependent binding to nucleic acids by the N-terminal zinc finger of the HIV-1 nucleocapsid protein: NMR structure of the complex with the Psi-site analog, dACGCC. AB - The nucleic acid interactive properties of a synthetic peptide with sequence of the N-terminal CCHC zinc finger (CCHC = Cys-X2-Cys-X4-His-X4-Cys; X = variable amino acid) of the human immunodeficiency virus (HIV) nucleocapsid protein, Zn(HIV1-F1), have been studied by 1H NMR spectroscopy. Titration of Zn(HIV1-F1) with oligodeoxyribonucleic acids containing different nucleotide sequences reveals, for the first time, sequence-dependent binding that requires the presence of at least one guanosine residue for tight complex formation. The dynamics of complex formation are sensitive to the nature of the residues adjacent to guanosine, with residues on the 3' side of guanosine having the largest influence. An oligodeoxyribonucleotide with sequence corresponding to a portion of the HIV-1 psi-packaging signal, d(ACGCC), forms a relatively tight complex with Zn(HIV1-F1) (Kd = 5 x 10(-6) M). Two-dimensional nuclear Overhauser effect (NOESY) data indicate that the bound nucleic acid exists predominantly in a single-stranded, A-helical conformation, and the presence of more than a dozen intermolecular NOE cross peaks enabled three-dimensional modeling of the complex. The nucleic acid binds within a hydrophobic cleft on the peptide surface. This hydrophobic cleft is defined by the side chains of residues Val1, Phe4, Ile12, and Ala13. Backbone amide protons of Phe4 and Ala13 and the backbone carbonyl oxygen of Lys2 that lie within this cleft appear to form hydrogen bonds with the guanosine O6 and N1H atoms, respectively. In addition, the positively charged side chain of Arg14 is ideally positioned for electrostatic interactions with the phosphodiester backbone of the nucleic acid. The structural findings provide a rationalization for the general conservation of these hydrophobic and basic residues in CCHC zinc fingers, and are consistent with site-directed mutagenesis results that implicate these residues as direct participants in viral genome recognition. PMID- 8443589 TI - Disulfide bonding patterns and protein topologies. AB - This paper examines the topological properties of protein disulfide bonding patterns. First, a description of these patterns in terms of partially directed graphs is developed. The topologically distinct disulfide bonding patterns available to a polypeptide chain containing n disulfide bonds are enumerated, and their symmetry and reducibility properties are examined. The theoretical probabilities are calculated that a randomly chosen pattern of n bonds will have any combination of symmetry and reducibility properties, given that all patterns have equal probability of being chosen. Next, the National Biomedical Research Foundation protein sequence and Brookhaven National Laboratories protein structure (PDB) databases are examined, and the occurrences of disulfide bonding patterns in them are determined. The frequencies of symmetric and/or reducible patterns are found to exceed theoretical predictions based on equiprobable pattern selection. Kauzmann's model, in which disulfide bonds form during random encounters as the chain assumes random coil conformations, finds that bonds are more likely to form with near neighbor cysteines than with remote cysteines. The observed frequencies of occurrence of disulfide patterns are found here to be virtually uncorrelated with the predictions of this alternative random bonding model. These results strongly suggest that disulfide bond pattern formation is not the result of random factors, but instead is a directed process. Finally, the PDB structure database is examined to determine the extrinsic topologies of polypeptides containing disulfide bonds. A complete survey of all structures in the database found no instances in which two loops formed by disulfide bonds within the same polypeptide chain are topologically linked. Similarly, no instances are found in which two loops present on different polypeptide chains in a structure are catenated. Further, no examples of topologically knotted loops occur. In contrast, pseudolinking has been found to be a relatively frequent event. These results show a complete avoidance of nontrivial topological entanglements that is unlikely to be the result of chance events. A hypothesis is presented to account for some of these observations. PMID- 8443590 TI - Modeling alpha-helical transmembrane domains: the calculation and use of substitution tables for lipid-facing residues. AB - Amino acid substitution tables are calculated for residues in membrane proteins where the side chain is accessible to the lipid. The analysis is based upon the knowledge of the three-dimensional structures of two homologous bacterial photosynthetic reaction centers and alignments of their sequences with the sequences of related proteins. The patterns of residue substitutions show that the lipid-accessible residues are less conserved and have distinctly different substitution patterns from the inaccessible residues in water-soluble proteins. The observed substitutions obtained from sequence alignments of transmembrane regions (identified from, e.g., hydrophobicity analysis) can be compared with the patterns derived from the substitution tables to predict the accessibility of residues to the lipid. A Fourier transform method, similar to that used for the calculation of a hydrophobic moment, is used to detect periodicity in the predicted accessibility that is compatible with the presence of an alpha-helix. If the putative transmembrane region is identified as helical, then the buried and exposed faces can be discriminated. The presence of charged residues on the lipid-exposed face can help to identify the regions that are in contact with the polar environment on the borders of the bilayer, and the construction of a meaningful three-dimensional model is then possible. This method is tested on an alignment of bacteriorhodopsin and two related sequences for which there are structural data at near atomic resolution. PMID- 8443591 TI - Helical peptides with three pairs of Asp-Arg and Glu-Arg residues in different orientations and spacings. AB - The helix-stabilizing effects of repeating pairs of Asp-Arg and Glu-Arg residues have been characterized using a peptide system of the same design used earlier to study Glu-Lys (Marqusee, S. & Baldwin, R.L., 1987, Proc. Natl. Acad. Sci. USA 84, 8898-8902) and Asp-Lys ion pairs (Marqusee, S. & Baldwin, R.L., 1990, In Protein Folding [Gierasch, L.M. & King, J., Eds.], pp. 85-94, AAAS, Washington, D.C.). The consequences of breaking ion pair and charge-helix dipole interactions by titration to pH 2 have been compared with the results of screening these interactions with NaCl at pH 7.0 and pH 2.5. The four peptides in each set contain three pairs of acidic (A) and basic (B) residues spaced either i, i + 4 or i, i + 3 apart. In one peptide of each kind the pairwise order of residues is AB, with the charges oriented favorably to the helix macrodipole, and in the other peptide the order is BA. The results are as follows: (1) Remarkably, both Asp-Arg and Glu-Arg peptides show the same pattern of helix stabilization at pH 7.0 found earlier for Glu-Lys and Asp-Lys peptides: i + 4 AB > i + 4 BA approximately i + 3 AB > i + 3 BA. (2) The ion pairs and charge-helix dipole interactions cannot be cleanly separated, but the results suggest that both interactions make important contributions to helix stability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8443592 TI - Identification of tyrosines 154 and 307 in the extracellular domain and 653 and 766 in the intracellular domain as phosphorylation sites in the heparin-binding fibroblast growth factor receptor tyrosine kinase (flg). AB - Four tyrosine residues have been identified as phosphorylation sites in the tyrosine kinase isoform of the heparin-binding fibroblast growth factor receptor flg (FGF-R1). Baculoviral-insect cell-derived recombinant FGF-R1 was phosphorylated and fragmented with trypsin while immobilized on heparin-agarose beads. Phosphotyrosine peptides were purified by chromatography on immobilized anti-phosphotyrosine antibody and analyzed by Edman degradation and electrospray tandem mass spectrometry. Tyrosine residue 653, which is in a homologous spatial position to major autophosphorylation sites in the catalytic domain of the src and insulin receptor kinases, is the major intracellular FGF-R1 phosphorylation site. Residue 766 in the COOH-terminus outside the kinase domain is a secondary site. Tyrosine residues 154 and 307, which are in the extracellular domain of transmembrane receptor isoforms and are in an unusual sequence context for tyrosine phosphorylation, were also phosphorylated. PMID- 8443593 TI - Increasing nitrogenase catalytic efficiency for MgATP by changing serine 16 of its Fe protein to threonine: use of Mn2+ to show interaction of serine 16 with Mg2+. AB - MgATP-binding and hydrolysis are an integral part of the nitrogenase catalytic mechanism. We are exploring the function of MgATP hydrolysis in this reaction by analyzing the properties of the Fe protein (FeP) component of Azotobacter vinelandii nitrogenase altered by site-directed mutagenesis. We have previously (Seefeldt, L.C., Morgan, T.V., Dean, D.R., & Mortenson, L.E., 1992, J. Biol. Chem. 267, 6680-6688) identified a region near the N-terminus of FeP that is involved in interaction with MgATP. This region of FeP is homologous to the well known nucleotide-binding motif GXXXXGKS/T. In the present work, we examined the function of the four hydroxyl-containing amino acids immediately C-terminal to the conserved lysine 15 that is involved in interaction with the gamma-phosphate of MgATP. We have established, by altering independently Thr 17, Thr 18, and Thr 19 to alanine, that a hydroxyl-containing residue is not needed at these positions for FeP to function. In contrast, an hydroxyl-containing amino acid at position 16 was found to be critical for FeP function. When the strictly conserved Ser 16 was altered to Ala, Cys, Asp, or Gly, the FeP did not support N2 fixation when expressed in place of the wild-type FeP in A. vinelandii. Altering Ser 16 to Thr (S16T), however, resulted in the expression of an FeP that was partially active. This S16T FeP was purified to homogeneity, and its biochemical examination allowed us to assign a catalytic function to this hydroxyl group in the nitrogenase mechanism. Of particular importance was the finding that the S16T FeP had a significantly higher affinity for MgATP than the wild-type FeP, with a measured Km of 20 microM compared to the wild-type FeP Km of 220 microM. This increased kinetic affinity for MgATP was reflected in a significantly stronger binding of the S16T FeP for MgATP. In contrast, the affinity for MgADP, which binds at the same site as MgATP, was unchanged. The catalytic efficiency (kcat/Km) of S16T FeP was found to be 5.3-fold higher than for the wild-type FeP, with the S16T FeP supporting up to 10 times greater nitrogenase activity at low MgATP concentrations. This indicates a role for the hydroxyl group at position 16 in interaction with MgATP but not MgADP. The site of interaction of this residue was further defined by examining the properties of wild-type and S16T FePs in utilizing MnATP compared with MgATP.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8443594 TI - Cost of failure to project impact of protein science on human health and economy. PMID- 8443595 TI - The protein import machinery of mitochondria. PMID- 8443596 TI - Characterization and 2D NMR study of the stable [9-21, 15-27] 2 disulfide intermediate in the folding of the 3 disulfide trypsin inhibitor EETI II. AB - The three disulfide Ecballium elaterium trypsin inhibitor II (EETI II) reduction with dithiothreitol (DTT) and reoxidation of the fully reduced derivative have been examined. A common stable intermediate has been observed for both processes. Isolation and sequencing of carboxymethylated material showed that the intermediate lacks the [2-19] bridge. The NMR study showed a very strong structural conservation as compared to the native EETI II, suggesting that the bridges are the [9-21] and [15-27] native ones. The differences occurred in sections 2-7 (containing the free cysteine 2 and the Arg 4-Ile 5 active site) and 19-21 (containing the second free cysteine). Distance geometry calculations and restrained molecular dynamics refinements were also in favor of a [9-21, 15-27] arrangement and resulted in a well-conserved (7-28) segment. PMID- 8443597 TI - Sequence and expression of the gene for N10-formyltetrahydrofolate synthetase from Clostridium cylindrosporum. AB - Sau3 A and Hind III restriction fragments of Clostridium cylindrosporum genomic DNA were used to isolate clones containing 80% of the N10-H4folate synthetase gene in a 5' fragment and the remaining 20% of the gene in the 3' fragment. These fragments were joined at a common SnaB I restriction site and expressed in Escherichia coli at a level equivalent to what is normally found in C. cylindrosporum. Sequence comparisons show a large degree of homology with genes from two other clostridial species, including a thermophile. Certain conserved sequences found in the three clostridial proteins and in the N10-H4folate synthetase portion of eukaryotic C1-H4folate synthases may represent consensus sequences for nucleotide and H4folate binding. PMID- 8443598 TI - Modulation of antibody affinity by a non-contact residue. AB - Antibody LB4, produced by a spontaneous variant of the murine anti-digoxin monoclonal antibody 26-10, has an affinity for digoxin two orders of magnitude lower than that of the parent antibody due to replacement of serine with phenylalanine at position 52 of the heavy chain variable region (Schildbach, J.F., Panka, D.J., Parks, D.R., et al., 1991, J. Biol. Chem. 266, 4640-4647). To examine the basis for the decreased affinity, a panel of engineered antibodies with substitutions at position 52 was created, and their affinities for digoxin were measured. The antibody affinities decreased concomitantly with increasing size of the substituted side chains, although the shape of the side chains also influenced affinity. The crystal structure of the 26-10 Fab complexed with digoxin (P.D.J., R.K. Strong, L.C. Sieker, C. Chang, R.L. Campbell, G.A. Petsko, E.H., M.N.M., & S.S., submitted for publication) shows that the serine at heavy chain position 52 is not in contact with hapten, but is adjacent to a tyrosine at heavy chain position 33 that is a contact residue. The mutant antibodies were modeled by applying a conformational search procedure to position side chains, using the 26-10 Fab crystal structure as a starting point. The results suggest that each of the substituted side chains may be accommodated within the antibody without substantial structural rearrangement, and that none of these substituted side chains are able to contact hapten. These modeling results are consistent with the substituents at position 52 having only an indirect influence upon antibody affinity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8443599 TI - Analysis of sequence requirements for protein tyrosine sulfation. AB - We analyzed sequences surrounding known tyrosine sulfation sites to determine the characteristics that distinguish these sites from those that do not undergo sulfation. Tests evaluated the number and position of acidic, basic, hydrophobic, and small amino acids, as well as disulfide and N-glycosylation (sugar) sites. We determined that composition-based tests that select close to 100% of known tyrosine sulfation sites reject 97% of the non-sulfated tyrosines. The acidic test, by far the most selective, eliminated 95% of the non-sulfated tyrosine residues and none of the sulfated tyrosines. Including the basic, hydrophobic, and disulfide tests increased the elimination rate to 97%. Whereas no position flanking the tyrosine residues had the same amino acid always present, imperfectly conserved amino acids found in some positions will improve the specificity of the tests. PMID- 8443600 TI - Identification of a nucleic acid-binding region within the largest subunit of Drosophila melanogaster RNA polymerase II. AB - The largest and the second-largest subunit of the multisubunit eukaryotic RNA polymerases are involved in interaction with the DNA template and the nascent RNA chain. Using Southwestern DNA-binding techniques and nitrocellulose filter binding assays of bacterially expressed fusion proteins, we have identified a region of the largest, 215-kDa, subunit of Drosophila RNA polymerase II that has the potential to bind nucleic acids nonspecifically. This nucleic acid-binding region is located between amino acid residues 309-384 and is highly conserved within the largest subunits of eukaryotic and bacterial RNA polymerases. A homology to a region of the DNA-binding cleft of Escherichia coli DNA polymerase I involved in binding of the newly synthesized DNA duplex provides indirect evidence that the nucleic acid-binding region of the largest subunit participates in interaction with double-stranded nucleic acids during transcription. The nonspecific DNA-binding behavior of the region is similar to that observed for the native enzyme in nitrocellulose filter binding assays and that of the separated largest subunit in Southwestern assays. A high content of basic amino acid residues is consistent with the electrostatic nature of nonspecific DNA binding by RNA polymerases. PMID- 8443602 TI - A study of intermediates involved in the folding pathway for recombinant human macrophage colony-stimulating factor (M-CSF): evidence for two distinct folding pathways. AB - The folding pathway for a 150-amino acid recombinant form of the dimeric cytokine human macrophage colony-stimulating factor (M-CSF) has been studied. All 14 cysteine residues in the biologically active homodimer are involved in disulfide linkages. The structural characteristics of folding intermediates blocked with iodoacetamide reveal a rapid formation of a small amount of a non-native dimeric intermediate species followed by a slow progression via both monomeric and dimeric intermediates to the native dimer. The transition from monomer to fully folded dimer is complete within 25 h at room temperature at pH 9.0. The blocked intermediates are stable under conditions of sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and thus represent various dimeric and folded monomeric species of the protein with different numbers of disulfide bridges. Peptide mapping and electrospray ionization mass spectrometry revealed that a folded monomeric species of M-CSF contained three of the four native disulfide bridges, and this folded monomer also showed some biological activity in a cell-based assay. The results presented here strongly suggest that M-CSF can fold via two different pathways, one involving monomeric intermediates and another involving only dimeric intermediates. PMID- 8443601 TI - Retroviral nucleocapsid proteins possess potent nucleic acid strand renaturation activity. AB - The nucleocapsid protein (NC) is the major genomic RNA binding protein that plays integral roles in the structure and replication of all animal retroviruses. In this report, select biochemical properties of recombinant Mason-Pfizer monkey virus (MPMV) and HIV-1 NCs are compared. Evidence is presented that two types of saturated Zn2 NC-polynucleotide complexes can be formed under conditions of low [NaCl] that differ in apparent site-size (n = 8 vs. n = 14). The formation of one or the other complex appears dependent on the molar ratio of NC to RNA nucleotide with the putative low site-size mode apparently predominating under conditions of protein excess. Both MPMV and HIV-1 NCs kinetically facilitate the renaturation of two complementary DNA strands, suggesting that this is a general property of retroviral NCs. NC proteins increase the second-order rate constant for renaturation of a 149-bp DNA fragment by more than four orders of magnitude over that obtained in the absence of protein at 37 degrees C. The protein-assisted rate is 100-200-fold faster than that obtained at 68 degrees C, 1 M NaCl, solution conditions considered to be optimal for strand renaturation. Provided that sufficient NC is present to coat all strands, the presence of 400-1,000-fold excess nonhomologous DNA does not greatly affect the reaction rate. The HIV-1 NC mediated renaturation reaction functions stoichiometrically, requiring a saturated strand of DNA nucleotide:NC ratio of about 7-8, rather than 14. Under conditions of less protein, the rate acceleration is not realized. The finding of significant nucleic acid strand renaturation activity may have important implications for various events of reverse transcription particularly in initiation and cDNA strand transfer. PMID- 8443603 TI - Exploration of subsite binding specificity of human cathepsin D through kinetics and rule-based molecular modeling. AB - The family of aspartic proteinases includes several human enzymes that may play roles in both physiological and pathophysiological processes. The human lysosomal aspartic proteinase cathepsin D is thought to function in the normal degradation of intracellular and endocytosed proteins but has also emerged as a prognostic indicator of breast tumor invasiveness. Presented here are results from a continuing effort to elucidate the factors that contribute to specificity of ligand binding at individual subsites within the cathepsin D active site. The synthetic peptide Lys-Pro-Ile-Glu-Phe*Nph-Arg-Leu has proven to be an excellent chromogenic substrate for cathepsin D yielding a value of kcat/Km = 0.92 x 10(-6) s-1 M-1 for enzyme isolated from human placenta. In contrast, the peptide Lys-Pro Ala-Lys-Phe*Nph-Arg-Leu and all derivatives with Ala-Lys in the P3-P2 positions are either not cleaved at all or cleaved with extremely poor efficiency. To explore the binding requirements of the S3 and S2 subsites of cathepsin D, a series of synthetic peptides was prepared with systematic replacements at the P2 position fixing either Ile or Ala in P3. Kinetic parameters were determined using both human placenta cathepsin D and recombinant human fibroblast cathepsin D expressed in Escherichia coli. A rule-based structural model of human cathepsin D, constructed on the basis of known three-dimensional structures of other aspartic proteinases, was utilized in an effort to rationalize the observed substrate selectivity. PMID- 8443604 TI - An automated method for modeling proteins on known templates using distance geometry. AB - We present an automated method incorporated into a software package, FOLDER, to fold a protein sequence on a given three-dimensional (3D) template. Starting with the sequence alignment of a family of homologous proteins, tertiary structures are modeled using the known 3D structure of one member of the family as a template. Homologous interatomic distances from the template are used as constraints. For nonhomologous regions in the model protein, the lower and the upper bounds for the interatomic distances are imposed by steric constraints and the globular dimensions of the template, respectively. Distance geometry is used to embed an ensemble of structures consistent with these distance bounds. Structures are selected from this ensemble based on minimal distance error criteria, after a penalty function optimization step. These structures are then refined using energy optimization methods. The method is tested by simulating the alpha-chain of horse hemoglobin using the alpha-chain of human hemoglobin as the template and by comparing the generated models with the crystal structure of the alpha-chain of horse hemoglobin. We also test the packing efficiency of this method by reconstructing the atomic positions of the interior side chains beyond C beta atoms of a protein domain from a known 3D structure. In both test cases, models retain the template constraints and any additionally imposed constraints while the packing of the interior residues is optimized with no short contacts or bond deformations. To demonstrate the use of this method in simulating structures of proteins with nonhomologous disulfides, we construct a model of murine interleukin (IL)-4 using the NMR structure of human IL-4 as the template. The resulting geometry of the nonhomologous disulfide in the model structure for murine IL-4 is consistent with standard disulfide geometry. PMID- 8443605 TI - Amino acid sequence of human lens beta B2-crystallin. PMID- 8443606 TI - The story of a toxic protein, 1888-1992. PMID- 8443608 TI - 1993 resolutions for successful staff developers. PMID- 8443607 TI - The what and why of CQI: getting staff into it. PMID- 8443609 TI - School affiliations: from contracts or orientation. PMID- 8443610 TI - The seven steps of consulting. PMID- 8443611 TI - Workplace literacy: meeting change head-on. PMID- 8443612 TI - Laughter and learning. PMID- 8443613 TI - Four tools to facilitate management development. PMID- 8443614 TI - The pervasive developmental disorder spectrum: a case illustration. AB - Children diagnosed with a pervasive developmental disorder experience difficulties along a spectrum of severity. Impairments in socialization, communication, and the ability to appropriately express and interpret affect in relationships are common features of the disorder. After summarizing salient thinking in the field, the author describes a case emphasizing the individual psychotherapy process in which the patient was involved. Although individual psychotherapy with such patients is currently viewed with skepticism, the one-on one relationship may be a central feature of such treatment because it can serve as a model for other relationships. The author advocates a multimodal treatment plan appropriately geared to the needs of such patients. PMID- 8443615 TI - The autonomous self. AB - Although the nature of the self has become a central issue in psychoanalysis, a comprehensive theory of its origin and development is needed. In an effort to elaborate one such theory, the author first reviews the history of psychoanalytic conceptualizations of the self. He then examines extra-clinical evidence from literature, philosophy, and the social sciences to gain additional insight into the persistent features of the self. Finally, he outlines some unique characteristics of the human self in light of new insights from modern evolutionary biology. PMID- 8443616 TI - The laying on of health: personality patterns of psychic healers. AB - Twenty-six psychic healers who claimed to heal by way of touch were studied with psychological tests to see whether they had personality characteristics in common. The consistencies they showed could be conceptualized in a way that sheds light on the nature of all healing. PMID- 8443617 TI - Body and self in feminine development: implications for eating disorders and delicate self-mutilation. AB - Eating disorders and the syndrome of delicate self-mutilation are primarily afflictions of women. The author examines this preponderance in light of the hypothesis that women's body experiences are inherently more ambiguous and recalcitrant than those of men, and women are thus both more alienated from and more attuned to their bodies than are men. After reviewing normal female development, the author explores the dynamics of the frequent coexistence in women of eating disorders and delicate self-mutilation. PMID- 8443618 TI - Measures of mental representation: clinical and theoretical considerations. AB - The authors explored the strengths and limitations of measures of mental representation from attachment theory and object relations theory. Using a study of adolescent mothers' mental representations while pregnant and their association to later mother-infant attachment (Levine, Tuber, Slade, & Ward, 1991), they compared the Adult Attachment Interview (AAI) (George, Kaplan, & Main, 1985) and the Krohn Object Representation Scale (KORS) (Krohn & Mayman, 1974) in terms of their clinical and theoretical utility. The authors argue that the AAI does not sufficiently explicate less adaptive object-representations, and that attachment research must address a broader clinical population to have a greater heuristic impact on clinical theory and practice. The AAI relies less on clinical inference than the KORS, however, thus providing a more viable mechanism for predicting parent-child relationship patterns. Clinical examples are provided to illustrate the process and content of the two scoring systems. PMID- 8443619 TI - The role of personality in the treatment of schizophrenic and schizoaffective disorder inpatients: a pilot study. AB - As a prelude to a prospective study of personality functioning in chronically psychotic patients, the medical records of 736 hospitalized schizophrenic and schizoaffective disorder patients were retrospectively reviewed. The authors found much higher rates of Axis II personality disorder (PD) diagnoses among patients on extended-care inpatient units, which was consistent with their belief that clinicians on these units were using Axis II labels to document concurrent as well as premorbid personality factors. In addition, patients with PD diagnoses had significantly different courses of inpatient treatment, as documented by length-of-stay data. Level of function at discharge did not differ between those with and without PD diagnoses. The authors posit various hypotheses about these findings and discuss difficult conceptual and methodological issues regarding the influence of personality factors in schizophrenia. PMID- 8443620 TI - Bone marrow transplantation for sickle cell anaemia. PMID- 8443621 TI - Flexible working in general practice. PMID- 8443622 TI - Adaptable pharmacy. PMID- 8443623 TI - Quality in medical education and training. AB - Quality in medical education and training is difficult to define, and even more difficult to monitor. To ease these tasks a working party in the North East Thames Region produced a contract-monitoring document to act as a framework for monitoring the contract between clinical tutors and the postgraduate dean. PMID- 8443624 TI - Heterotopic ossification. AB - Heterotopic ossification is well recognized following trauma to the head and spinal cord, total hip arthroplasty and internal fixation of acetabular fractures. Fortunately, effective prophylactic measures exist to minimize this occasionally devastating complication. This article reviews the pathophysiological events involved in heterotopic bone formation and outlines its clinical presentation and management. PMID- 8443625 TI - Cardioversion in atrial fibrillation. AB - Atrial fibrillation is a common rhythm disorder but is frequently not managed aggressively. Cardioversion to sinus rhythm is beneficial and has a high success rate. It should be considered in all patients with atrial fibrillation. PMID- 8443626 TI - Intrathecal baclofen in severe spasticity. AB - Control of severe spasticity and its associated features with administration of baclofen directly into the CSF via an intrathecal pump has radically improved the management of patients resistant to oral therapy. This article reviews the rationale and clinical indications for this technique, and the outcome and complications encountered. PMID- 8443627 TI - Management of retinal vein occlusion. AB - Retinal vein occlusion is a common cause of visual loss. The clinical features, pathogenesis, aetiology and management of this condition are presented and discussed. It is an advantage to involve both the physician and the ophthalmologist in the management of the condition. PMID- 8443628 TI - Didronel PMO. AB - Didronel PMO is a new treatment, comprising cyclical disodium etidronate and calcium carbonate, for women with postmenopausal osteoporosis who already have one or more vertebral fractures. Vertebral fracture rates can be reduced by 50% after treatment for 2 years. PMID- 8443629 TI - How to make a business plan. AB - The writing of a business plan is not the most important part of formulating a plan. Much more important is the consultation and dialogue with interested parties that should precede the writing stage. This article identifies the pitfalls that might snare the uninformed. PMID- 8443630 TI - Management of detrusor instability. AB - Detrusor instability is a socially disabling condition of unknown aetiology which may cause diurnal urinary frequency, urgency and incontinence in either sex. Current management of this characteristically fluctuating disease ranges from simple conservative measures through behavioural and medical therapy to endoscopic and major abdominal surgery. PMID- 8443631 TI - Adult adenoids. PMID- 8443633 TI - Surgery as a career option for women. PMID- 8443632 TI - Reducing the risks of paediatric transport. PMID- 8443634 TI - British Society for Rheumatology, Xth annual general meeting. North Yorkshire, 24 26 March 1993. Abstract. PMID- 8443635 TI - Monocyte expression of class II antigens. PMID- 8443636 TI - Screening for breast cancer. PMID- 8443637 TI - Future directions for conservative treatment of gallbladder calculi. AB - Recent conservative gallstone treatments provide rapid relief from symptoms, but all have a potential for stone recurrence. They are indicated in patients who are unfit or unwilling to undergo cholecystectomy. Wider application will depend on selection of patients who are at least risk of recurrence, or on development of effective prophylactic strategies. PMID- 8443638 TI - Pancreatic infection complicating acute pancreatitis. AB - Pancreatic infection is the leading cause of death from acute pancreatitis. Patients with severe necrotizing pancreatitis are most at risk. Early computed tomography and percutaneous fine-needle aspiration microbiology of areas of pancreatic necrosis enable early diagnosis. Pancreatic infection should be treated surgically, although sterile necrosis may be managed conservatively. The role of antimicrobial drugs is uncertain. PMID- 8443639 TI - Interleukin 2 therapy: current role in surgical oncological practice. AB - The use of recombinant interleukin 2 (rIL-2) in clinical practice has opened up new and beneficial avenues in the treatment of certain malignant diseases. Although rIL-2 can stimulate a range of host antitumour defence mechanisms, only 30-40 per cent of patients who are treated will respond to such therapy as assessed by a reduction in tumour volume. The effect of rIL-2-based treatment schedules on delaying progression of disease and on overall survival in comparison with standard current treatments and chemotherapeutic regimens is not clear. Randomized clinical trials are required to evaluate precisely the role of rIL-2 in various therapeutic combinations and to ascertain the optimum therapeutic regimens for individual tumour types. Studies currently under way should provide more insight into the possible beneficial effects of immunotherapy with rIL-2. More basic research is required to ascertain how rIL-2 may produce its antitumour effects and why the therapeutic results obtained in humans have been so selective and less beneficial than those in experimental animals. PMID- 8443640 TI - Quality-of-life measurement in surgical practice. AB - Assessment of quality of life is gaining momentum in areas of medical practice where standard measures of outcome are not sensitive enough to determine treatment strategies. Such methods have not been widely adopted in the surgical specialties, although this is changing. The techniques used are easily understood but they have not been standardized and are subject to several confounding factors. Nevertheless, quality-of-life measurement may provide additional information in the research environment and surgical audit. PMID- 8443641 TI - Carotid endarterectomy improves haemodynamics on the contralateral side: implications for operating contralateral to an occluded carotid artery. AB - The importance of the patency of the contralateral carotid artery on the haemodynamic effect of a carotid stenosis was investigated. The breath-holding index was used to estimate cerebral perfusion reserve. The percentage rise in middle cerebral blood flow velocity, measured by transcranial Doppler ultrasonography, occurring during breath-holding was divided by the time of breath-holding. In study 1, ten subjects with no carotid stenosis, 13 with unilateral and eight with bilateral stenosis were studied. For unilateral stenosis the breath-holding index was reduced on the stenosed side compared with normal (0.85 versus 1.34 per cent per s, P < 0.05). For bilateral disease, in the presence of severe stenosis on the side contralateral to that being examined, even a moderate stenosis (30-50 per cent) resulted in a much greater reduction in the breath-holding index. In study 2, the breath-holding index was measured before and after carotid endarterectomy in ten patients. The index increased significantly following operation, not only on the operated side (1.31 versus 0.79 per cent per s, P < 0.01), but also on the contralateral side (1.23 versus 0.87 per cent per s, P < 0.05). In three of four patients with contralateral stenosis > 90 per cent or occlusion, operation improved the breath-holding index markedly (> 90 per cent) on the non-operated side above the stenosis or occlusion. These results demonstrate the importance of patency of the contralateral carotid artery in determining the haemodynamic effect of a carotid stenosis. In addition, operating contralateral to an occlusion may improve haemodynamic status above the occlusion. Implications in selecting patients for carotid endarterectomy are discussed. PMID- 8443643 TI - Critical leg ischaemia: an appraisal of clinical definitions. Joint Vascular Research Group. AB - The reliable prediction of imminent limb death remains a clinical problem. The International Vascular Symposium and European working parties each produced similar definitions of 'critical ischaemia', but this is the first attempt to address the issue with prospectively collected data. Complete 3-year follow-up data were available for 213 patients. In addition to the above two definitions, a simplified modification has been evaluated, after review of the data 1 year into this study. All three definitions were able to identify patients likely to require amputation in the absence of successful reconstruction. The sensitivity, specificity and positive predictive values with which they were able to do so was, however, poor. None of the definitions was able to predict which diabetic patients would require amputation. Diabetics were more likely to undergo amputation than non-diabetics. There was, however, no significant difference in the initial ankle artery pressures between the diabetic and non-diabetic patient subgroups. None of the definitions reliably predicted which grafts would occlude, in which event the 3-year mortality rate was approximately 35 per cent. Critical ischaemia by any of these definitions is associated with a high mortality rate. Arterial reconstruction is associated with a reduction in both mortality and amputation rates These data do not support the hypothesis that critical ischaemia is associated with a greater graft occlusion rate than lesser degrees of severe ischaemia. PMID- 8443642 TI - Prospective randomized comparison of in situ and reversed infrapopliteal vein grafts. AB - A three-centre prospective randomized trial was undertaken to compare the efficacy of in situ and reversed saphenous vein grafts for long bypasses to tibial and peroneal arteries. Of 162 patients entered into the study, 82 received an in situ graft and 80 a reversed vein graft. All operations were for limb salvage and the two groups of patients were well matched for age, sex, incidence of diabetes, smoking habits and coronary artery disease. At a maximum follow-up of 3 years there were 48 primary graft failures: 19 in the in situ group and 29 in the reversed vein group. Of these, three in situ grafts and seven reversed grafts were salvaged by secondary intervention. Secondary cumulative patency rates calculated at 3 years after operation were 68 and 66 per cent respectively for in situ and reversed grafts (P not significant). Cumulative limb salvage rates were 78 per cent for in situ grafts and 87 per cent for reversed grafts (P not significant). Separate analysis of a subgroup with small veins (< or = 3.5 mm minimum diameter) showed cumulative patency rates at 2 years of 74 per cent for in situ grafts and 60 per cent for reversed grafts (P not significant). These results indicate that for veins > 3.5 mm in diameter the in situ and reversed techniques for operation are equally effective. Some doubt remains about the best way of using smaller veins; a large number of such veins need to be studied to resolve this question. PMID- 8443644 TI - Intermittent claudication incites systemic neutrophil activation and increased vascular permeability. AB - Reperfusion following severe ischaemia incites a systemic response involving neutrophil activation and vascular injury. Recent work suggests that intermittent claudication may also be capable of inducing similar changes, reversible by revascularization. This observation may have implications for the treatment of claudication and explain the high associated cardiovascular mortality. This hypothesis was investigated using an in vivo model. Rats underwent repeated hindlimb stimulation after common iliac artery ligation. Intravital fluorescence microscopy was used to observe postcapillary venules of the tibialis anterior muscle in the hindlimb. This revealed a bilateral increase in leucocyte endothelial adhesion and vascular permeability to albumin after unilateral subtotal ischaemia and muscle stimulation, associated with increased urinary albumin excretion. These results provide further evidence supporting the association of intermittent claudication with potentially deleterious systemic manifestations. PMID- 8443645 TI - The future of vascular surgery. PMID- 8443646 TI - Access to convalescent beds in vascular surgery. PMID- 8443647 TI - Interventional radiology in the maintenance of infrainguinal vein graft patency. AB - The impact of interventional radiology on the cumulative patency rate of 112 consecutive infrainguinal vein grafts was reviewed. The primary, primary assisted and secondary cumulative patency rates at 42 months were 40, 65 and 69 per cent respectively. The difference between primary and primary assisted patency rates (40 versus 65 per cent, P = 0.001) resulted from the early detection and treatment of stenoses in 30 grafts by percutaneous transluminal angioplasty (PTA). Interventional radiology also improved the cumulative graft patency rate through PTA of one inflow and five outflow arteries, thrombolysis of two graft occlusions, embolization of two persistent arteriovenous fistulas and salvage of one graft on the first day after operation by percutaneous aspiration of distal graft thrombus. Interventional radiology has a crucial role to play in the maintenance of infrainguinal vein graft patency; provided that graft stenoses are detected early in their development by aggressive graft surveillance, PTA is a highly effective treatment. PMID- 8443648 TI - Early results and 1-year follow-up after intra-arterial thrombolysis. AB - Intra-arterial thrombolysis (IAT) was used as first-line treatment for 100 occlusions causing acute, subacute or chronic ischaemia. Streptokinase was used in 90 cases and tissue plasminogen activator in the remaining ten. Complete lysis, as determined radiologically, was achieved in 55 per cent of cases and partial lysis in 20 per cent. Lysis was more effective the earlier it was used. Major complications occurred in seven cases: five patients suffered major haemorrhage, two of whom died, and two had haemorrhagic cerebrovascular accidents. Of the patients with complete or partial clearance of thrombosis, 19 had no underlying apparent cause, 23 underwent angioplasty and 15 had an operation. The 1-year patency rate following complete lysis was 58 per cent. The 1-year patency rate after successful treatment commencing within 1 week of symptoms starting was 71 per cent, compared with 36 per cent for later treatment. Aortofemoral bifurcation grafts were cleared in three of five cases and all remain patent. Eight popliteal aneurysms were demonstrated by IAT and were ligated and bypassed; all these grafts remained patent at follow-up. IAT is less effective in chronic than acute occlusion. It should be reserved for patients in whom the occlusion is of short duration or for those with a thrombosed aortofemoral bifurcation graft or popliteal aneurysm. PMID- 8443649 TI - Effect of foot compression on the velocity and volume of blood flow in the deep veins. AB - The A-V Impulse System reduces the incidence of deep vein thrombosis by pneumatically compressing the venae comitantes of the lateral plantar artery, causing an increase in the velocity of blood in the proximal axial veins. Using a duplex scanner the effects of altering the pressure, pulse duration and frequency of foot compression on the velocity and volume of blood flow in the superficial femoral and popliteal veins were quantified. In 20 legs, foot compression of 50, 125 and 200 mmHg significantly increased the maximum venous blood flow by 9.0, 13.4 and 15.1 ml/s respectively (P < 0.001). Conversely, reducing the frequency of compression from 6 to 3 cycles per min significantly increased the rise in peak flow from 10.1 to 14.8 ml/s (P < 0.001). Changing the duration of compression from 1 to 3 s had no significant effect on peak flow. Increased blood flow is best achieved with high-pressure low-frequency foot compression. Increasing the duration of compression beyond 1 s has no effect on augmentation of flow in the deep veins. PMID- 8443650 TI - Emergency aortic aneurysmectomy in a renal transplant recipient. PMID- 8443651 TI - Survey of minor surgery in general practice in the west of Scotland. AB - Since April 1990 certain minor surgical procedures have attracted an item-of service payment for general practitioners (GPs). A postal survey was undertaken to obtain information about minor surgery in general practice in the West of Scotland and to find out whether further postgraduate education is required in this field. From a random stratified sample of 356 GPs, 311 (87.4 per cent) responded. Practitioners on health board minor surgery lists have increased minor surgery activity since April 1990; they prefer to perform the less technically demanding and time-consuming procedures on the eligible list. It is concluded that there is scope for increasing postgraduate education in minor surgery for GPs. PMID- 8443652 TI - Changes in major histocompatibility complex class II expression in monocytes and T cells of patients developing infection after surgery. AB - Expression of class II major histocompatibility complex (MHC) on monocytes is a prerequisite for effective antigen presentation and processing, an important component of the immune response to infection. It has been reported that the level of monocyte class II expression may identify patients who go on to develop infective complications following trauma. In the present study, flow cytometry was used to measure MHC class II (human leucocyte antigen (HLA)-DR) expression on circulating monocytes and T cells in 36 patients undergoing elective major resectional surgery, of whom 12 developed septic complications. The percentage of HLA-DR positive monocytes fell significantly on the first day after operation in both groups (P < 0.001) but was significantly higher in those without than in those with sepsis on days 1, 3 and 5 (P < 0.05). In contrast, the level of T cell HLA-DR expression rose significantly on the first day after operation (P < 0.05) in patients without sepsis to a level higher than in those who developed infection (P < 0.05). These findings have important implications, as predictive biological elements and for biological response modification, in patients at risk of developing sepsis after surgery. PMID- 8443653 TI - Diagnosis of traumatic rupture of the right hemidiaphragm by thoracoscopy. PMID- 8443654 TI - Easy technique for cholangiography during laparoscopic cholecystectomy. PMID- 8443655 TI - Pneumoperitoneum from a ruptured bronchus in a child. PMID- 8443656 TI - Resuscitation for haemorrhagic shock. PMID- 8443657 TI - Abdominal aortic thrombosis following a fall. PMID- 8443658 TI - Use of an accident and emergency department observation ward in the management of head injury. AB - The management of 405 patients presenting with head injury to an accident and emergency department was assessed. Sixty-nine patients were admitted, although this number should have been 127 according to current guidelines on the management of head injury. Only three attenders were admitted inappropriately according to these guidelines. An accident and emergency observation ward was open on weekdays only; at weekends, patients with head injury were admitted to a general surgical ward. When the observation ward was open, 51 of the 76 patients (67 per cent) presenting with admission criteria were admitted. When closed, only 15 of the 51 patients (29 per cent) with these criteria were admitted. Guidelines were applied effectively to reduce the number of unnecessary admissions, but there was a significant number of patients with minor head injury who were discharged inappropriately. This number was much reduced when an observation ward was available. PMID- 8443659 TI - Helicopter Emergency Medical Service operating from the Royal London Hospital: the first year. AB - The additional workload on the support hospital created by using a helicopter for emergency trauma has been assessed in the first year of operation. A total of 135 patients were brought to the Royal London Hospital, of whom 30 died, 34 were transferred for convalescence or rehabilitation to another hospital, and 71 discharged home. The median Injury Severity Score was 17 (range 0-75) and 82 patients (60.7 per cent) had a reduced Revised Trauma Score at the scene. Blunt injury greatly outnumbered penetrating trauma (117 versus 15 patients). Accidental injuries accounted for 77.0 per cent of the total, self-inflicted wounds 14.1 per cent and assaults 8.9 per cent. Parameters employed to assess workload were hospital bed-days used (total 2361), operations (118, occupying 287 h of theatre time) and blood transfusion (total 702 units used). The second 6 month study period showed a considerable increase in the number of patients admitted (102 versus 33) because of increased efficiency in call-out procedures. PMID- 8443660 TI - A family with dual inheritance of primary hyperparathyroidism and haemophilia. PMID- 8443661 TI - Phaeochromocytoma associated with thymoma. PMID- 8443662 TI - Vomiting caused by a dialysis fluid 'pseudocyst'. PMID- 8443663 TI - Laparoscopic mobilization and exteriorization for minimally invasive small bowel resection. PMID- 8443665 TI - Femoral hernia: intestinal obstruction is an unrecognized source of morbidity and mortality. AB - A total of 180 consecutive femoral hernia repairs, consisting of 100 emergency and 80 elective admissions between January 1979 and December 1986, were reviewed. Morbidity was greater in the emergency than in the elective group (P < 0.01) and was significantly related to intestinal obstruction (P < 0.001), a feature not previously highlighted. Intestinal obstruction also had an important association with mortality, which was confined to patients undergoing emergency surgery. Patients with intestinal obstruction are a high-risk group and require careful perioperative management. Wound infection predisposed to recurrence of femoral hernia (P < 0.01). Repair of recurrent hernia in patients treated electively was associated with an increased incidence of chest infection (P < 0.001). Prophylactic measures, including antibiotics, may help to reduce recurrence and its associated morbidity. Patients referred with an inguinal lump or hernia, as opposed to a femoral hernia, had a later outpatient appointment and consequently a later operation date (P < 0.02). All elderly patients referred with any groin lump should receive an early outpatient appointment. PMID- 8443664 TI - Crohn's disease and anastomotic recurrence: microvascular ischaemia and anastomotic healing in an animal model. AB - Microvascular injury and ischaemia may be factors in anastomotic recurrence after resection for Crohn's disease. This hypothesis was explored in a ferret model of multifocal intestinal infarction. At laparotomy, isolated loops of small intestine were injected intraarterially with styrene microspheres (test loop) or saline (control). At a second laparotomy 72 h later, test and control loops were divided and an end-to-end anastomosis performed between test loops (n = 2), test and control loops (n = 9) or control loops (n = 2). Abnormalities including chronic transmural inflammation, ulceration and granuloma formation were identified 2 weeks after the second operation in ten of the 11 surviving animals; changes were confined to the test loops and were more prominent adjacent to the anastomosis. No abnormalities were seen in control loops. The combination of two self-limiting ischaemic insults can produce a pattern of intestinal inflammation similar to that seen in anastomotic recurrence in Crohn's disease. PMID- 8443666 TI - Comparative study of abdominal incision techniques. AB - The characteristics of surgical incisions made with an electrosurgical technique were compared with those made using conventional methods in a prospective randomized trial. In particular, the claim that the method of incision may influence postoperative pain was investigated. A total of 101 consecutive patients receiving full-length midline laparotomy incisions for gastrointestinal resection were studied. A record was kept of the time required to make the incision and blood loss as well as postoperative pain (using a linear analogue scale), ventilatory function and requirement for analgesia. There were 50 patients in group 1 (scalpel; 15 men, 35 women) and 51 in group 2 (electrocautery; 26 men, 25 women). The groups were similar in age, body-weight, diagnosis and the type of surgical procedures being performed. Incision time was similar in the two groups but median blood loss during incision was significantly less in group 2 patients than in group 1 (10 versus 25 ml, P < 0.0001). Linear analogue pain scores were not significantly different between the groups at any stage after operation. The same was true of postoperative ventilatory function and requirement for analgesia. A total value for morphine use during the entire postoperative period was derived for each group and the median was 1.55 mg/kg for group 1 compared with 1.49 mg/kg for group 2. The electrosurgical method is associated with less blood loss during incision, although this study has failed to confirm any reduction in postoperative pain or requirement for analgesia in these patients. PMID- 8443667 TI - Sutureless laparoscopic treatment of perforated duodenal ulcer. PMID- 8443668 TI - Laparoscopic truncal vagotomy without drainage. PMID- 8443669 TI - Porcine islet isolation: prospective comparison of automated and manual methods of pancreatic collagenase digestion. AB - A prospective study was undertaken to compare an automated method of porcine pancreatic digestion with a simpler manual procedure. These techniques have not previously been compared directly. After intraductal distension with collagenase, seven porcine pancreata were divided longitudinally; half of each was digested by the automated method and half by the manual technique. Islet yield and purity were measured. Compared with the manual technique, the automated method isolated a significantly greater total volume of islet tissue (median (range) 3.56 (1.39 5.30) versus 1.07 (0.46-1.92) mm3/g, P = 0.022), increased the median (range) number of 105-microns islet equivalents isolated (5875 (2294-8746) versus 1766 (759-3168) per g, P = 0.022) and improved the islet cleavage index (median (range) 92 (89-99) versus 82 (78-92) per cent, P = 0.035). It is concluded that, although the automated method is more complicated to set up, it greatly improves the yield of intact islets from the porcine pancreas. PMID- 8443670 TI - Selective cholangiography in laparoscopic cholecystectomy. AB - Laparoscopic cholecystectomy is now the method of choice for removing the diseased gallbladder. Asymptomatic common bile duct stones occur in approximately 6 per cent of patients. Controversy exists, however, as to whether selective or routine peroperative cholangiography should be performed during laparoscopic cholecystectomy. Over a 21-month period 300 consecutive laparoscopic cholecystectomies without routine cholangiography were attempted. There were 28 conversions. In all, 229 patients did not undergo cholangiography and in this group there were two common duct injuries. These were both identified and dealt with by open operation. Five patients underwent peroperative cholangiography, none of whom was found to have common duct pathology. Endoscopic retrograde cholangiopancreatography was performed in 38 patients. Of 27 who had this investigation performed before operation, common duct stones were diagnosed in seven (26 per cent). Two common duct stones were discovered in 11 patients who underwent the investigation after operation. Thus only two of 240 patients (0.8 per cent) who did not undergo preoperative or peroperative cholangiography subsequently had symptomatic duct stones. Peroperative cholangiography may be indicated in selected patients who have had symptoms of common bile duct stones or in those in whom the biliary anatomy is unclear. However, routine preoperative or peroperative cholangiography is unnecessary during laparoscopic cholecystectomy. PMID- 8443671 TI - Laparoscopic cholecystectomy with endoscopic retrograde cholangiopancreatography for acute gallstone pancreatitis. PMID- 8443672 TI - Transanal division of an apical pouch bridge after restorative proctocolectomy with a J shaped reservoir. PMID- 8443673 TI - Individuals with a strong family history of colorectal cancer demonstrate abnormal rectal mucosal proliferation. AB - Thirty-seven individuals with an increased lifetime risk of colorectal cancer because of family history and a control group (n = 21) with no such family history underwent colonoscopy. No neoplastic lesion was found in any individual. Rectal biopsies of macroscopically normal mucosa were taken 8 cm from the anal margin and mucosal proliferation assessed by the crypt cell production rate (CCPR). There was no difference in CCPR between the control group (median 10 (95 per cent confidence interval 7-11) cells per crypt per h) and those at intermediate risk (lifetime risk between 1:17 and 1:10, n = 14). However, there was a significant difference in CCPR between the control group and those at higher risk (lifetime risk > 1:10, n = 23) (median CCPR 13 (95 per cent confidence interval 10-17) cells per crypt per h, P = 0.004). A high risk of colorectal cancer derived from family history correlates with an increased colorectal mucosal proliferation rate. PMID- 8443674 TI - Life quality and psychological morbidity with an ileostomy. AB - The recent introduction of restorative proctocolectomy for the treatment of ulcerative colitis has reopened the debate about the effects of ileostomy on quality of life. This study analysed life quality and psychological morbidity in 113 patients with an ileostomy using a postal questionnaire which included questions about their opinion of the pouch operation. Of the questionnaires, 73 per cent were suitable for analysis. A total of 93 per cent of those responding were happy with the ileostomy and appeared to have adapted to a normal life with it. Some 87 per cent stated that they would keep the ileostomy in preference to an ileoanal pouch. In addition, psychological morbidity as assessed by the General Health Questionnaire occurred in only 5 per cent of patients. PMID- 8443675 TI - Internal anal sphincter dysfunction in neurogenic faecal incontinence. AB - Forty-eight patients of median age 57 years with neurogenic faecal incontinence and 44 normal subjects of median age 51 years underwent fine-wire anal sphincter electromyography and anal manometry. The median (interquartile range (i.q.r.)) internal anal sphincter (IAS) electromyogram frequency was 0.26 (0.21-0.32) Hz for patients with faecal incontinence and 0.44 (0.31-0.55) Hz for controls (P < 0.01). The median (i.q.r.) ambulatory resting pressure was 48 (34-68) cmH2O for patients and 86 (72-102) cmH2O for controls (P < 0.01) and median (i.q.r.) frequency of transient IAS relaxations 9 (7-12) and 4 (3-7) per h respectively (P < 0.05). Mid-anal pressure fell to a greater extent in patients with incontinence during these episodes of transient IAS relaxation. Rectal pressure during such relaxation did not exceed mid-anal canal pressure in controls; for the patient group, rectal pressure increased during relaxation and exceeded mid-anal canal pressure in 36 cases. Frequent abnormal episodes of IAS relaxation may cause occult faecal leakage in patients with neurogenic faecal incontinence. PMID- 8443676 TI - An improved means of faecal diversion: the trephine stoma. PMID- 8443677 TI - Anatomy and function of the anal longitudinal muscle. PMID- 8443678 TI - Limitations of laser treatment for malignant dysphagia. PMID- 8443679 TI - Safety of fibreoptic endoscopy: analysis of cardiorespiratory events. PMID- 8443680 TI - Laparoscopic versus open appendicectomy: a prospective evaluation. PMID- 8443681 TI - Place of routine operative cholangiography at cholecystectomy. PMID- 8443682 TI - Potential candidates for small bowel transplantation. PMID- 8443683 TI - Breast cancer: the unacknowledged epidemic. PMID- 8443684 TI - Bone changes in postmenopausal Spanish women. AB - Total body bone mass (TBBM), axial bone mass (trunk = chest and spine), and peripheral bone mass (arms and legs) were determined in 258 normal, slow bone mass loser, postmenopausal women, as determined by previous biochemical studies, in order to study the degree of bone mass reduction due to menopause. The subjects of this study were divided into 5-year groups on a year-since-menopause basis. The first group corresponded to 1-5 years since menopause, and the last group to 25 years or over since menopause. An important and significant reduction in trunk bone mass (-12.3%, P < 0.001) and TBBD (-5.8%, P < 0.002), without changes in head, arms, and legs was observed in the first 5-year group. In the next 5-year group, a significant reduction was observed in all body areas, but at a higher rate in the peripheral skeleton (-9% in arms and -7.3% in legs). A slow down in bone mass loss was observed in the period between 10 and 25 years since menopause. These values became significant again after 25 years since menopause at the axial (-28.9%, P < 0.001) and TBBD (-20.3%, P < 0.05) level. Aside from providing percentages of bone mass reduction with respect to age and time since menopause, these data also indicate that measurements of specific body areas may not be extrapolated to others due to different loss in different body areas, and that there is a marked bone loss rate in the axial skeleton in the first 5 years since menopause. PMID- 8443685 TI - Aromatase activity in human osteoblast-like osteosarcoma cell. AB - Aromatase activity was studied in cultured human osteosarcoma cell (HOS). HOS was incubated from 12 to 72 hours with 10(-10) M-10(-5) M dexamethasone. Aromatase activity was determined by measuring [3H]H2O released upon the conversion of [1 beta-3H]androstenedione to estrone. HOS showed aromatase activity, and apparent km for [1 beta-3H]androstenedione was 4.46 +/- 0.98 nm (mean +/- SD). The aromatase activity was significantly increased by 10(-9) M-10(-5) M dexamethasone in a dose-dependent manner. Dexamethasone increased Vmax of aromatase activity but did not change its km value. These results suggest that osteoblastic cells have aromatase activity which is regulated by glucocorticoid, and directly convert androgen to estrogen in itself. PMID- 8443687 TI - Effects of the calcium channel blocker nifedipine on epiphyseal growth plate and bone turnover: a study in rabbit. AB - The potential effects of a calcium channel blocker (nifedipine) on epiphyseal growth plate and bone remodeling have been investigated in growing rabbits. The treated group received 6 mg/kg/day nifedipine twice daily by gavage for 10 weeks. An untreated group was used as control; with this dose, neither toxic effects nor decrease in the body weight have been observed. No modifications of blood phosphocalcic parameters have been found. In the treated group there is a significant lower cancellous bone volume, lower osteogenesis, shorter labeled perimeters, and lower mineral apposition rate than in the control group. Epiphyseal growth plate thickness is lower than in the untreated animals and considerable morphological changes are observed in the growth zone compared with the control group. A decrease in the growth of humerus length was found. In conclusion, nifedipine affects bone physiology, especially with consequences on bone growth. These effects appear to be quantitatively important, and there is the possibility of bone side effects on therapeutic use in humans, especially in young subjects. PMID- 8443686 TI - Determination of proliferative characteristics of growth plate chondrocytes by labeling with bromodeoxyuridine. AB - Postnatal bone growth occurs by the process of endochondral ossification in cartilaginous growth plates at the ends of long bones. The rate and extent of long bone growth is determined by a combination of chondrocytic proliferation, matrix production, and increase in chondrocytic height in the direction of growth during cellular enlargement. In this study, single pulse and/or repeated pulse labeling with the thymidine analog bromodeoxyuridine (BrdU) was used to study the role of cellular proliferation in controlling long bone growth. Variables studied included progression of the label over time following a pulse, and patterns and progression of the label over time following repeated pulse labeling for 24 and 48 hours. Examination was made of the proliferative characteristics of chondrocytes, the spatial pattern of cellular proliferation, and cell cycle kinetics. With respect to the spatial pattern of proliferative chondrocytes, results suggest that chondrocytes within a column are more synchronized with each other than are chondrocytes in different columns. This is consistent with the concept that each column represents a clonal expansion of a stem cell, which may proceed independently from adjacent columns. Despite this apparent heterogeneity, all chondrocytes in the proliferative zone complete at least one cell cycle in 24 28 hours. This estimate of the cell cycle time is significantly shorter than previous estimates of cell cycle times in similar growth plates. Our results also suggest that chondrocytes entering the cell cycle in the proximal part of the growth plate spend an average of 4 days in the proliferative cell zone, representing approximately four cellular divisions. After leaving the cell cycle, an additional 48 hours is required for the label to reach the terminal chondrocyte, which represents the time required to complete hypertrophy. These data are important when considering hypotheses concerning both the role of controls on proliferation in the determination of overall rate of long bone growth, as well as the interplay between proliferation and hypertrophy in regulating the overall amount of growth achieved by a given growth plate. PMID- 8443688 TI - Inhibitory effect of salmon calcitonin on bone resorption: morphological study of the tibial growth plate in rats. AB - Salmon calcitonin (sCT) at doses of 100 and 50 UI given subcutaneously to growing rats produced in vivo evidence of osteoclastic activity inhibition. Histological assessment was carried out by measuring the perichondrial ring of Lacroix height, and a dose-correlated effect was found. These aspects were coupled with an increase in the osteoclast number and suggested that in studies with bone resorption inhibitors, morphological evaluation based on osteoclasts count is not reliable. The changes of the metaphysis suggested also that sCT affects the activity of hypertrophic chondrocytes of the growth plate. Plasma calcium levels did not differ significantly between treated rats and controls; an increased phosphatemia was observed in sCT-treated animals. PMID- 8443689 TI - A mathematical model for fluoride uptake by the skeleton. AB - A mathematical model was developed that predicts fluoride accumulation and clearance from the skeleton based upon fluoride bioavailability, bone remodeling rate, and the fluoride binding characteristics of bone. It was assumed that fluoride binds to bone in a nonlinear fashion such that a smaller percentage of fluoride is bound to bone if fluoride intake is increased to high levels. Bone resorption rate was assumed to be proportional to the solubility of hydroxyfluoroapatite which is inversely related to bone fluoride content. The predictions made by the model compared favorably with experimental results from fluoride uptake and clearance studies. Parametric studies done using the model showed the following: (1) fluoride can be cleared from the skeleton by bone remodeling, but fluoride clearance takes over four times longer than does fluoride uptake; and (2) fluoride uptake by the skeleton was positively associated with bone remodeling rate. However, the concentration of fluoride in newly formed bone does not decrease with reduced remodeling rates and surpasses 10,000 ppm for intakes of fluoride greater than 9 mg/day. For osteoporosis, daily dose and duration of fluoride treatment should be selected to avoid reaching a toxic cumulative bone fluoride content. PMID- 8443690 TI - Immobilized DPP and other proteins modify OCP formation. AB - Osteonectin, gamma-carboxyglutamic acid-containing (Gla) protein, and dentin phosphoprotein were covalently attached to sepharose beads and inoculated in solutions at two different degrees of supersaturation with respect to both octacalcium phosphate (OCP) and hydroxyapatite. In both solutions, the inhibitory activity towards de novo formation of calcium phosphate that these proteins display when freely dissolved in solution was completely eliminated when they were immobilized on the sepharose at concentrations of up to 5 micrograms/mg wet beads. In the solution that was more highly supersaturated with respect to OCP, the immobilized dentin phosphoprotein, moreover, was found to induce de novo formation of OCP in proportion to the concentration of the protein immobilized. For example, at 10 micrograms/ml of the immobilized dentin phosphoprotein, the induction period was reduced more than 50%. However, in the solution considerably less supersaturated with respect to OCP, none of the immobilized proteins were capable of inducing OCP or apatite deposition. These findings suggest that the immobilized dentin phosphoprotein could work as a nucleating substrate for the OCP phase in solutions where calcium and phosphate concentrations are sufficiently higher than equilibrium saturation levels for the OCP phase. PMID- 8443691 TI - Decrease in bone levels of 1,25-dihydroxyvitamin D in women with subcapital fracture of the femur. AB - In a previous study we were able to show that in women over the age of 45 the level of 1,25-dihydroxyvitamin D (1,25(OH)2D) in bone, but not in serum, is significantly reduced when compared with younger women. In the present study we measured the concentration of 1,25(OH)2D in sera and bones of 19 female patients with subcapital fractures of the femur, mean age 78 +/- 2 years. We were able to show that serum levels of 1,25(OH)2D were within the normal range, while bone levels were markedly reduced compared to levels in femoral bone obtained from young female cadavers or to the previously reported levels in non-osteoporotic elderly women. Thus, reduced levels of 1,25(OH)2D in bones of elderly women may lead, together with other factors, to subcapital fractures. PMID- 8443692 TI - Serum tartrate-resistant acid phosphatase (TRAP) as a biochemical marker of bone remodeling. PMID- 8443693 TI - Ipriflavone: new insights into its mechanisms of action on bone remodeling. PMID- 8443695 TI - Cross-calibration of DXA equipment: upgrading from a Hologic QDR 1000/W to a QDR 2000. AB - In this study, the cross-calibration of a fan beam DXA system (Hologic QDR-2000) to a pencil beam scanner from the same manufacturer (Hologic QDR-1000/W) is described. The scanners were calibrated by the manufacturer using the same anthropomorphic spine phantom at installation. To verify consistent machine calibration, a group of 69 female subjects, aged 46-75, had anteroposterior (AP) spine and proximal femur scans on the QDR-1000/W followed by pencil and array scans of the same sites on the QDR-2000 during the same visit. Many of the subjects had bilateral examinations of the proximal femur for a total of 123 hip scans. Pencil and array area, bone mineral content (BMC), and bone mineral density (BMD) from the QDR-2000 were compared with the values obtained on the QDR 1000/W, and linear regression equations were derived for relating the two instruments. At the spine, no differences were found between the QDR-1000/W BMD values and the QDR-2000 array BMD values. A slight difference between pencil beam modes was detected but was not deemed clinically significant. Linear regression models relating the QDR-2000 and QDR-1000/W AP spine BMD measurements showed correlation coefficients greater than 0.99, with slopes of 1.00, intercepts equivalent to zero, and small root mean square errors. Comparisons at the proximal femur showed equivalency at the femoral neck and trochanter regions for the two machines in pencil mode, but slight increases in BMC and BMD at the other femoral sites on the QDR-2000 in both pencil and array mode. Correlation coefficients were 0.97-0.99 for all measurement regions except for Ward's.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8443694 TI - Demonstration of TGF-beta 1 mRNA by in situ hybridization in normal human fracture healing. AB - The role of transforming growth factor beta (TGF-beta) in fracture healing has previously been investigated in a rodent model, but not in human material. We investigated TGF-beta 1 gene expression in specimens of callus from normally healing human fractures, using in situ hybridization to a cDNA TGF-beta 1 probe and an autoradiographic disclosure system. TGF-beta 1 mRNA was present in areas of proliferation of mesenchymal tissue, bone, and cartilage. Levels of expression were lower in cells in the fracture hematoma and in differentiated (hypertrophic) chondrocytes. These results are compatible with those found in various animal models using immunohistochemistry and support the view that locally produced TGF beta 1 is a regulator of fracture repair in humans from the early (mesenchymal proliferation) stage to the stage of remodeling of woven bone. They also indicate that, for TGF-beta 1, animal models accurately reflect human bone repair. PMID- 8443696 TI - Read my hips: measuring trochanteric soft tissue thickness. AB - There is considerable uncertainty about which factors best predict hip fractures in the elderly. We have previously shown that a global measure of body habitus, the body mass index (BMI), is an important predictor of hip fracture in this age group. BMI may serve as a surrogate measure of trochanteric soft tissue thickness. To determine a more local assessment of trochanteric soft tissue, we compared trochanteric soft tissue thickness by ultrasound to other local measures of trochanteric soft tissue thickness (by dual-energy X-ray absorptiometry [DXA] and hip circumference) and global measures of body habitus [body mass index (BMI), bioelectrical impedance analysis (BIA), hip/waist circumference] in 50 healthy, community-dwelling women [72 +/- 4 years old (mean +/- SD)]. Ultrasound was highly correlated with DXA trochanteric soft tissue (r2 = 0.815, P < 0.0001), hip circumference (r2 = 0.810, P < 0.0001), BMI (r2 = 0.721, P < 0.0001), and BIA (r2 = 0.743, P < 0.0001). Trochanteric soft tissue thickness measured by DXA was also significantly (P < 0.0001) correlated with BMI and BIA. We conclude that local assessments of trochanteric soft tissue thickness, including DXA and hip circumference, provide an easy and noninvasive technique to assess trochanteric soft tissue thickness. PMID- 8443697 TI - Long- and short-term side effects and safety of calcitonin in man: a prospective study. AB - Forty-three patients were treated for a total duration of 301 patient-years with calcitonin (CT) (range 3-16 years, median duration 6 years 6 months). Eighty-four percent of patients were suffering from complications associated with Paget's disease and the remainder from osteoporosis. In the majority of patients, CT was administered by the subcutaneous route and one patient was psychologically dependent on calcitonin injections. There were no long-term side effects associated with CT therapy. In a separate group of 105 patients consisting of 83 patients on human CT and 22 patients on salmon CT, injections showed short-term side effects in 77% and 64% of these patients, respectively (NS). Side effects associated with nasally administered salmon CT in 25 patients were mild and of low incidence (32%). Long-term administration of calcitonin in humans is safe and devoid of any serious or long-term side effects. PMID- 8443698 TI - Spine and femur density and broadband ultrasound attenuation of the calcaneus in normal Spanish women. AB - Bone density of the spine and femoral neck and broadband ultrasound attenuation of the calcaneus were measured in 111 normal Spanish women between the ages of 30 and 70 years. The cross-sectional study showed that spine and hip density decreased by 36 and 29%, respectively, and the ultrasound attenuation value decreased by 32% between 30 and 70 years of age. The rate of bone loss at the three sites was significant in women over age 50 and in postmenopausal women. These normative data will be helpful in assessing bone mass in Spanish women suspected of having osteoporosis. PMID- 8443699 TI - The new patient experience putting your best foot forward. AB - By implementing a consistent new patient experience, your practice will have put its best foot forward. It's the first step toward achieving your next challenge: turning new patients into established patients. This requires you to provide quality dentistry and a high level of service during each and every patient visit. PMID- 8443700 TI - The ultimate dental office team member. PMID- 8443701 TI - A case of a hepatitis B infected practitioner. AB - The first case of a dental practitioner infected by a blood-borne pathogen to be identified to the College of Dental Surgeons of B.C. and reviewed by the Dental Profession Advisory Program's infected practitioner program committee is reported. After the committee was contacted, the infected practitioner's status was evaluated and guidelines were provided to him. This paper reviews the committee's decision-making process, particularly with respect to its management of the infected dental practitioner. PMID- 8443702 TI - Planning for income tax: a case study. PMID- 8443703 TI - Ontario dentists: 1. Radiologic practices and opinions. AB - In February 1991, about 10 per cent of Ontario's general dentists were polled via a mail survey to gather information about their radiological practices and opinions. Responses were received from 413 out of 537 general practitioners, for a response rate of 77 per cent. A large majority of dentists (86 per cent) have no written office policy and/or protocol for selecting patients for X-ray examination, and just over half (54 per cent) primarily use clinical experience to select patients for these examinations. In the majority of practices (57 per cent), radiographs of asymptomatic recall patients are taken after both their history and clinical examination are complete. A similar percentage (56 per cent) of dentists are opposed to explicit guidelines for radiological examinations. PMID- 8443704 TI - Ontario dentists: 2. Bitewing utilization and restorative treatment decisions. AB - Guidelines for the selection of patients requiring radiological examination have recently been published in Canada and the United States. The purpose of this paper, the second in a three-part series on the results of a questionnaire to Ontario general practitioners, is to compare bitewing use in Ontario against the U.S. guidelines. This questionnaire determined the frequency of recall bitewing examination for low and high caries risk patients, as well as the factors that influence the diagnostic and treatment decisions of the responding dentists. For example, 49 to 78 per cent of dentists order recall bitewings--in accordance with U.S. guidelines--for their patients in individual low caries risk categories. Similarly, 49 to 88 per cent of dentists order recall bitewings for individual patients in high caries risk categories, which is also consistent with the U.S. guidelines. However, across all low and high caries risk groups of patients, the percentages of dentists who followed the recommended guidelines were 34 and 15 per cent, respectively. The responding dentists' estimates of the length of time required for caries to progress through enamel are indirectly associated with the interval prescribed for recall bitewing examination. PMID- 8443705 TI - Twin block appliances. PMID- 8443706 TI - Ontario dentists: 3. Radiographs prescribed in general practice. AB - In February 1991, a mail survey was used to poll a sample consisting of about 10 per cent of Ontario's general dentists. The data obtained provided information about the radiographs prescribed by dentists for five different patient types, which were described to the respondents. The per cent agreement between the radiographic procedures prescribed by Ontario dentists and the ADA-approved Center for Devices and Radiological Health (CDRH) guidelines ranged from three per cent to 79 per cent, depending on patient type and disease risk. For each patient and risk type, there was considerable variation in the radiographs prescribed. PMID- 8443707 TI - Communication. PMID- 8443708 TI - Early clinical evaluation of four new bonding resins used for conservative restoration of cervical erosion lesions. PMID- 8443709 TI - Hi-tech/hi-care dentistry. PMID- 8443710 TI - Blood use in resuscitation after trauma. PMID- 8443711 TI - Forearm-plate removal. PMID- 8443712 TI - Retroperitoneal lymphadenectomy. PMID- 8443713 TI - Training the general surgeon. PMID- 8443714 TI - The use of blood in resuscitation of the trauma patient. AB - The ability to transfuse blood (a form of tissue transplantation) with relatively few immediate and long-term complications has led to increased survival in victims of injury who require massive amounts of blood. The primary deficit in hypovolemic shock secondary to trauma is in oxygen transport to the hypoperfused tissues; therefore, blood transfusion has an essential role in therapy during resuscitation and definitive treatment. The major immediate complications to be avoided are hypothermia and acidosis, which are the main causes of the coagulopathy associated with massive transfusion. The most worrisome long-term complication is the transmission of disease, of which hepatitis C is the most frequent. With improved screening techniques and heightened donor awareness, the risk of disease transmission is less than 2%. Until synthetic oxygen-carrying solutions are available, the transfusion of red blood cells, when appropriately indicated, will remain an important component in the resuscitation of the trauma patient. PMID- 8443715 TI - The Maintenance of Competence (MOCOMP) Program: motivating specialists to appraise the quality of their continuing medical education activities. AB - The goal of the Maintenance of Competence (MOCOMP) Pilot Project is to develop a comprehensive CME strategy that will motivate specialists to continuously update their clinical practice. In its 1st year the pilot program has taken several significant steps. A credit system has been implemented to facilitate recognition of CME of the highest educational quality and to encourage specialists to compare their CME efforts with those of their colleagues. The self-directed CME curriculum currently followed by the typical MOCOMP Program member has been described. A diary has been implemented for specialists to record CME activities and their potential impact on practice. The MOCOMP Program is the first attempt to motivate self-directed continuing medical education (CME) through the use of a diary and the first attempt to use this instrument to encourage critical appraisal of personal CME habits. PMID- 8443716 TI - Outpatient laser cone biopsy under local anesthesia. AB - The authors report on 60 patients who had abnormal findings on cervical cytologic examination, necessitating conization of the cervix. The procedure was done in an ambulatory setting, with a carbon-dioxide laser unit and local anesthesia. The average operative time was 16.9 minutes. Fifty-one (85%) patients experienced no complications, and there were no cases of excessive bleeding. In all patients, the specimen was satisfactory for histologic review. Only 5% (three) of patients would have preferred to have the procedure performed under general anesthesia. Laser cone biopsy of the cervix can be performed in an outpatient setting, with local anesthesia. Morbidity is minimal and there is potential for economic saving when compared with conventional methods for biopsy of the cervix. PMID- 8443717 TI - Disseminated leiomyomatosis peritonealis: report of a case in a postmenopausal woman. AB - Disseminated leiomyomatosis peritonealis (DLP) is a rare condition that to date has been reported only in premenopausal women. The author reports a case of DPL occurring in a postmenopausal woman who had undergone total hysterectomy 30 years before and had received no hormonal therapy subsequently. The lesions were multiple and consisted of smooth-muscle cells that proliferated from medium-sized blood vessels. The author concludes that the patient's lesions likely represent a histologic variant of DLP. PMID- 8443718 TI - Spontaneous rupture of the spleen in patients with infectious mononucleosis. AB - The author describes two cases of spontaneous splenic rupture occurring with infectious mononucleosis in young, previously healthy patients. The reports illustrate the variable clinical presentation--from sudden, fatal hemorrhage to bleeding that stops spontaneously. Although conservative nonoperative treatment may be successful in carefully selected cases, laparotomy with splenectomy appears to be the safest therapeutic approach. When a nonoperative approach is selected, the patient should be observed in a critical-care facility with immediate access to an operating room. Normal activity should not be resumed until the spleen has returned to its normal size as demonstrated by computed tomography or ultrasonography. PMID- 8443719 TI - Sulfhydryl-containing agents in the treatment of gastric bleeding induced by nonsteroidal anti-inflammatory drugs. AB - In a double-blind study involving 172 patients, the author investigated the effect of sulfhydryl-containing agents (cysteine and methylmethionine sulfonium chloride [MMSC]) on hematemesis resulting from erosive gastritis induced by nonsteroidal anti-inflammatory drugs. The 56 patients who received cysteine (200 mg orally four times a day) and the 59 patients who received MMSC (500 mg orally four times a day) were significantly (p < 0.01) more hemodynamically stable, with no rebleeding, than the 57 patients who made up a control group. Endoscopy carried out 48 hours after admission demonstrated that gastric erosions were still present in a significantly (p < 0.01) higher number of patients in the control group (20 [35%]) than in patients receiving cysteine (6 [11%]) and in patients receiving MMSC (7 [12%]). Eighteen patients (32%) in the control group required blood transfusion because of continued bleeding or rebleeding compared with only 3 patients (5%) receiving cysteine and 2 patients (3%) receiving MMSC (p < 0.01). Emergency surgery was necessary in 13 patients (23%) in the control group and in 1 patient (2%) in the group receiving cysteine who had rebleeding. Four patients in the control group died postoperatively. The results show that sulfhydryl-containing agents stimulate the healing of erosive gastritis induced by nonsteroidal anti-inflammatory drugs and protect against the complications of bleeding produced by the gastritis. PMID- 8443720 TI - Hematuria and intravenous pyelography in pediatric blunt renal trauma. AB - Because the traditional protocol for investigating blunt renal trauma in children has been questioned and because of societal awareness of health care costs, the authors carried out a retrospective review of blunt renal trauma in 138 children over a 5-year period to establish criteria for urgent radiologic investigation of those with suspected renal trauma. From their findings, they recommend that in the absence of the suspected major injuries and hypotension a threshold count of 40 red blood cells per high-power field is necessary before urgent intravenous pyelography should be done. PMID- 8443721 TI - Current management of choledocholithiasis. PMID- 8443722 TI - Laparoscopic gastrointestinal anastomoses. AB - In a preliminary study of laparoscopic gastrointestinal anastomosis, a gastric outlet obstruction was created under laparoscopic control in six domestic pigs, weighing an average of 25 kg. A simultaneous gastroenterostomy was formed with an end-stapling device. All animals recovered clinically, and good anastomotic healing was documented 1 week postoperatively. The authors suggest that an end stapling device could be one method of creating a gastrointestinal anastomosis for humans that is safe and reliable, allows rapid recovery and decreases hospital stay. PMID- 8443723 TI - Open cholecystectomy: its morbidity and mortality as a reference standard. AB - In a retrospective study of 10,471 cholecystectomies, performed between 1971 and 1990, the incidence and causes of death and morbidity of cholecystectomy were analysed. There were 47 postoperative deaths (0.4%); 6 deaths occurred in 5841 patients less than 50 years old, 23 in 3898 patients between 50 and 70 years old and 18 in 732 patients more than 70 years old. Death rates in each group were, respectively, 0.1%, 0.6% and 2.5% (p < 0.001). The death rate in 9339 patients who had cholecystectomy alone was 0.3% and the death rate in 1132 patients who had a concomitant common bile duct exploration (CBDE) was 1.6% (p < 0.001). Cardiovascular complications were the main cause of death, and biliary, pulmonary and wound complications were the most common. There were 614 complications in 529 patients; 176 of these patients were less than 50 years old, 252 were between 50 and 70 years old and 101 were more than 70 years old. Complication rates were, respectively, 3.0%, 6.5% and 13.8% (p < 0.001). For patients with cholecystectomy alone the morbidity was 3.6% and for patients who had a concomitant CBDE the morbidity was 17% (p < 0.001). The mortality and morbidity of cholecystectomy increase significantly with age and a concomitant CBDE. However, patients who underwent cholecystectomy electively or for acute cholecystitis had comparable mortality and morbidity. PMID- 8443724 TI - Endoscopic retrograde cholangiopancreatography in the management of choledocholithiasis with laparoscopic cholecystectomy. AB - With the advent of laparoscopic cholecystectomy, endoscopic retrograde cholangiopancreatography (ERCP) has an increasing role in perioperative management. To assess this role, the authors studied, retrospectively, 12 patients who underwent ERCP out of a series of 475 who had laparoscopic cholecystectomy. ERCP was indicated preoperatively for biliary colic in four patients, gallstone pancreatitis in two and common bile duct stone on ultrasonography in one. ERCP was performed postoperatively for jaundice in three patients, for cholangitis in one and for a positive intraoperative laparoscopic cholangiogram in one. Choledocholithiasis was diagnosed in six patients preoperatively and in three postoperatively. Only one patient had an unsuspected residual bile duct stone postoperatively. Of nine patients with stones, endoscopic sphincterotomy was performed in eight and stones were cleared in all with no complications; a stone passed spontaneously in the other patient. ERCP is indicated before laparoscopic cholecystectomy in cases of jaundice, gallstone pancreatitis, cholangitis, abnormal liver biochemistry suggesting cholestasis and ultrasonographic demonstration of either a common bile duct stone or a common bile duct greater than 8 mm in diameter. Operative laparoscopic cholangiography is indicated when the anatomy is unclear or the bile duct appears dilated. If choledocholithiasis is founded, the options include open or laparoscopic common bile duct exploration and intra- or postoperative endoscopic sphincterotomy. PMID- 8443725 TI - Anterior cervical corpectomy for the treatment of complex cervical lesions. AB - Instability and stenosis of the cervical spine have been treated by posterior decompression and anterior decompression with fusion. In this study the authors evaluate the results obtained in 31 patients who underwent anterior cervical corpectomy for compressive or unstable lesions of the cervical spine. Operative level, preoperative and postoperative symptoms and physical findings were assessed. Twenty-seven patients had preoperative neurologic symptoms and signs, including alterations in sensation, motor findings and reflexes. The average follow-up was 12 months, average number of disc spaces excised was 2.5 and average number of vertebral bodies excised was 1.6. With respect to relief of pain, results were good or excellent in 27 patients. All patients but one had union of the bone graft. No neurologic deterioration occurred. The authors believe that patients with compressive lesions of the cervical spine can benefit from anterior cervical corpectomy with fusion and that complications are minimal. PMID- 8443726 TI - Carcinoma of the prostate: case report. AB - The authors report a case of carcinoma of the prostate with an unusual presentation. The patient, an 80-year-old man, had swelling of the right buttock and right side of the lower abdomen, diffuse bony pain and increasing weakness of both lower limbs. He responded well to therapy. Aggressive management of previously untreated carcinoma is warranted even in elderly patients with metastatic disease. PMID- 8443727 TI - The spectrum of surgery in Ethiopia. AB - Ethiopia's need for surgical services is assessed from on-site reviews of operating-room records in various hospitals and compared with data from other countries. Information on surgical manpower and total operations for the country were obtained from the Ministry of Health of Ethiopia. In Ethiopia the ratio of surgeons to population is very low (0.32 surgeons per 100,000 population) and inadequate numbers of essential operations (e.g., cesarean section and inguinal hernia repair) are performed. The average age of the surgical patient is young (37 years), and men are operated on twice as frequently as women. Of the 9422 operations performed during 6 months in the central, regional and rural hospitals surveyed, 7037 (75%) could be performed by a general practitioner or a paramedic specially trained for the procedure and would not require a fully trained general surgeon. The implications for surgical manpower training are discussed. PMID- 8443728 TI - Assessment of the older woman. AB - Our knowledge of the aging woman will continue to grow, and that knowledge will begin with obtaining assessments that are appropriate and complete for this population. It is important to recognize that assessment can lead to improved diagnoses, more appropriate intervention, and improved outcomes, which hopefully will contribute to an improved quality of life for all older women. PMID- 8443729 TI - Factors influencing management of breast cancer in the elderly woman. AB - Elderly women have the same right as their younger counterparts to be a part of the decision-making process of their health care. Women with breast cancer should be informed of treatment options and the advantages and disadvantages of each choice as it applies to their individual circumstance. Clinical judgment should be used in patients with poor performance status and known limited life expectancy as to the optimal approach that will provide the best quality of life for the maximum duration but with acceptable risks to the patient. PMID- 8443730 TI - Ovarian, uterine, and cervical cancer in the elderly woman. AB - Older women are at a significantly increased risk of developing ovarian, endometrial, and cervical cancers. When an elderly woman develops one of these malignancies, she is more likely to die from it than a younger woman. The increased mortality-to-incidence ratio may be related primarily to the more advanced stage at diagnosis. Data suggest that elderly women in the United States are less likely to undergo routine gynecologic screening examinations than younger women, which often results in malignancies that are diagnosed at a more advanced stage. More aggressive screening programs directed at elderly women would likely result in an improvement of morbidity and mortality. Treatment modalities for the gynecologic malignancies presented include surgery, radiotherapy, and chemotherapy and must be carefully selected, planned, and sometimes modified for the elderly woman with intercurrent medical problems. There is no evidence that radical pelvic surgery is associated with increased morbidity in most elderly women compared with younger women. Treatment options such as radiotherapy may be associated with significant morbidity for elderly women. Most chemotherapeutic regimens are tolerated by elderly women, but modification of dose or agent may be necessary in selected cases. Improved screening and better treatments for gynecologic malignancies are needed for our nation's aging population. Studies specifically directed at the diagnosis, care, and treatment of elderly patients with gynecologic malignancies are necessary to improve the significant morbidity and mortality associated with ovarian, endometrial, and cervical cancers in elderly women. PMID- 8443731 TI - Current management of invasive squamous carcinoma of the vulva. AB - Because invasive vulvar cancer is generally discovered in elderly women, a careful pretreatment evaluation of the patient and the extent of her disease must be conducted. Thereafter, the treatment plan should be consistent with the principle of effective disease control with the minimum disruption and morbidity. It is essential to try to avoid overly aggressive surgeries that can commit the patient to prolonged hospitalization. The rarity of these lesions makes it essential to obtain appropriate consultation for the gynecologic oncologist who is most familiar with the condition. PMID- 8443732 TI - Age and gender as factors in cancer therapy. AB - Cancer is already a disease of the elderly, and this will be increasingly the case as US population demographics continue to shift. The existing patterns of care for older cancer patients must be changed to improve the current cancer survival statistics. High technology innovations are not a prerequisite to improve our current results. The current best standards of care for cancer screening and treatment must be applied to the older woman. Although older patients may seem more comfortable (at least to a physician) with a paternalistic style of practice than younger patients, it is not in their best interest to exclude them from participation in their care. The health professional's assessment of the older patient's quality of life may miss the mark, denying them curative treatments as a result. Health care providers must learn to take the time to include older patients in their medical care and to educate them about the benefits of screening and cancer treatment. PMID- 8443733 TI - Mental health and psychiatric disorders in older women. AB - An increase in the number and diversity of resources designed to optimize psychosocial function in people and especially women over age 65 is inevitable in the next decade as both the size and political influence of this group increase. The successful implementation of such programs is dependent on widespread change throughout society, involving many disparate groups, including older people themselves, politicians, health care administrators, and researchers from a range of disciplines. Clinicians in medicine and allied professions have a pivotal role in this regard. At present there are many reversible causes of psychiatric morbidity in the elderly, including depression, anxiety, cognitive defects, sensory impairment, malnutrition, and adverse effects of alcohol abuse and polypharmacy that are often not recognized or treated appropriately. It is therefore essential that family practitioners receive both undergraduate and postgraduate training to recognize and manage the wide range of psychosocial disorders prevalent in older women. Intervention may require little more than an opportunity for the women to ventilate concerns or obtain information and advice about community resources. In other circumstances in which there are complex interactions of physical, social, and psychological factors, optimal management may involve interventions that require specific skills beyond the scope of the individual practitioner. Referral to a psychogeriatric team is likely to be helpful in such situations. The team, with its access to a full range of health professionals and community resources, is well placed to deal economically with complex issues. The special care units are best equipped to manage the tertiary care of the chronically ill who do not have adequate community-based support available. Increased information derived from research relating to the spectrum of mental ill health and mental health is essential to adequately address the causes, correlates, and treatments of illness, and to answer questions about the positive aspects of mental health that may have implications for all age groups and both sexes. For example, it is intriguing that older women maintain a high level of psychological health despite greater social disadvantages than any other major section of the community. It is likely that psychological factors, such as better coping skills and ability to adapt to stressful life events, influence both the quality of life in older women and possibly also its duration. Alternatively, it is possible that the commonly held view that the life expectancies of women and men will converge as women undertake more of the roles and activities currently the province of men may occur.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8443734 TI - Mental health and the aging woman. AB - The role of the physician as guardian of elderly women's mental and physical health reaches far beyond prescribing medications for symptom relief. The role an elderly woman plays in family, community, and society, are integrally related to the symptoms she experiences. Protocols for evaluation should be taught early and consistently in medical training, and opportunities for creative, multifaceted problem solving should be provided. PMID- 8443735 TI - Substance abuse in older women. AB - Literature on elderly women and substance abuse is sparse. What data exist support the following conclusions: (1) older women are at risk for self medicating with prescription drugs and alcohol and have more risk for drug-drug and drug-alcohol interactions, (2) women are more likely to be prescribed psychotropics, (3) older women are at greater risk for prescription drug abuse by a physician or physicians than other age groups, (4) alcohol and drug abuse are likely to increase as younger women drinkers and drug users age, and this younger cohort will use more illicit drugs, and (5) the incidence of substance abuse remains underreported and underdiagnosed. PMID- 8443736 TI - Dermatologic and cosmetic concerns of the older woman. AB - The cutaneous signs of aging including wrinkles, solar lentigines ("liver spots"), and telangiectasias are primarily the result of repeated exposures to ultraviolet light (photoaging). Chronologic aging, and in women, estrogen withdrawal also exert an effect on the structure and function of the epidermis and dermis. In this article, the relative roles of these three factors are discussed, as are the most common skin lesions found in the older woman. Lastly, the therapeutic options available for the treatment of these age-associated cutaneous disorders are outlined. PMID- 8443737 TI - The influence of ethnicity on the health of older women. AB - There is increasing evidence that ethnicity is an important factor as one ages that serves as an integrating force to help an older woman filter her personal experience with aging and to pass through significant life changes, such as being a cultural and health resource for family and community, becoming a grandmother, retiring, or moving in with family when frailty occurs. Ethnicity also can act as a buffer to the visccitudes of old age. When the surrounding environment, especially the health care environment, encourages expression and the reaffirmation of ethnicity, we find examples of successful aging in many ethnic communities; however, aging is often less successful when poverty, lack of informal and or formal support, or dislocation through immigration or separation from ethnic community and family disrupt the process of coming to terms with old age. The process of counseling an older patient is a complex one, particularly when ethnicity is a strong factor in the patient's identity. Ethnicity acts as a filter to the aging process, influencing health, health beliefs and behavior, as well as interaction with health professionals. Many ethnic groups, while identifying and incorporating certain elements of scientifically based understanding of disease and illness into their lives, nevertheless also adhere to more traditional paradigms of health and illness, or associated health beliefs and behaviors sometimes called folk beliefs that diverge from mainstream Western scientific medical concepts. Older women, who are often more steeply versed in traditional health beliefs than men and often act as the first line of medical advice within the family, may adopt a combination of orthodox (scientific) and folk traditions to attempt to address illness or malaise. This multiple approach is not necessarily harmful; rather, many folk treatments (which include specific ritual behaviors, and use of teas and other folk remedies) may, from a strictly medical standpoint, play a neutral role in terms of biochemical activities but a highly positive role in terms of psychological well-being. Folk treatments allow an individual to address the social imbalances that are considered significant in causing a particular condition within the ethnic tradition. Health professionals who work with particular ethnic groups would benefit from a deeper understanding of cultural beliefs and practice, and an acknowledgement of respect for these practices. Among the variety of writings on ethnicity and health or ethnicity and aging that have appeared are practical texts on communication strategies with various ethnic groups.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8443738 TI - Gender, health, and responsible research. AB - In women, the prevention or management of diseases and disorders particular to middle-age, as well as those that do not present until later life, requires a substantially improved knowledge base to differentiate those conditions whose causes stem from ovarian hormone insufficiency (and thus are treatable by hormone therapy) from those that do not. Only then can we prevent misdiagnosis, avoid dismissing middle-aged women's medical complaints as "menopausal," and attempt to change the perception that physicians do not render the same attention to women or take women's health care concerns seriously. It is inevitable that dramatic changes in the health care system will be required to accommodate changing population demographics resulting from the burgeoning aging population. Currently, more than 35 million women, or one third of the total female population, is postmenopausal. Last year alone, the number of women reaching age 50 (the average age for menopause in the United States), reached 1.3 million, and this number will approach 2 million per year in the first decade of the 21st century as peak numbers of women from the baby-boom generation reach this milestone. Clearly, as the proportion of older women continues to grow, the need to expand our scientific and medical knowledge base assumes even greater urgency in order to develop efficacious strategies for the delivery of preventive, diagnostic, and clinical health care to older women. These strategies are crucial in reducing morbidity and maintaining the independence of this rapidly growing segment of the population. PMID- 8443739 TI - Menopause and hormone replacement therapy. AB - The beneficial impact of hormone replacement therapy on postmenopausal women is substantial. The size of the positive impact has probably been underestimated owing to compliance issues. Patients and physicians need to learn about the important contribution to preventive health care that occurs with estrogen. Negative beliefs about menopause by both patients and physicians may contribute to poor compliance with hormone replacement therapy. It is time to emphasize the positive aspects: the prospect for long life made healthy by a good preventive care program. PMID- 8443740 TI - Estrogens, lipids, and heart disease. AB - The routine prescription of hormone replacement therapy for elderly women to prevent heart disease is not indicated. Until better data are available, the use of estrogens primarily to prevent heart disease probably should be reserved for women at high risk by virtue of their LDL/HDL ratio or the presence of manifest coronary heart disease. There is no reason to give progestins to the woman without a uterus; unopposed oral estrogen should improve lipoproteins within a few weeks, and this change, if sustained, should reduce risk. The management of a woman with an intact uterus is more problematic given the unknowns about progestin's long-term effects on lipids or the heart and the unwillingness of many elderly women to resume regular (or irregular) bleeding. There are, however, many proven benefits of hormone replacement therapy, including the prevention of osteoporosis and urogenital atrophy. Decisions about when it is too late to start estrogen, or when it is time to stop it, will need to be made on a case-by-case basis. PMID- 8443741 TI - Osteoporosis and hip fracture. AB - Recent studies have identified multiple factors contributing to osteoporosis and hip fracture in women. It is now possible to identify individuals who are at increased risk of osteoporotic fractures through bone densitometry, so that appropriate measures for the prevention and restoration of bone loss can be instituted. Although largely experimental, such measures are available. Prevention of hip fracture, however, may best be accomplished by preventing falls or the trauma associated with the fall in those identified at increased risk. Promising interventions are also available to reduce those risks, e.g., exercise programs, cataract surgery, and environmental modification such as hand rails and foam-backed carpeting. A major factor contributing to fall-associated fractures is a decline in mental function. Here too there may be effective measures to alter this decline in mental function and specifically the central integration of sensory input. Clinicians await with great interest the results of the proposed intervention studies of the Women's Health Initiative evaluating vitamin D and hormone replacement therapy. PMID- 8443742 TI - Sexuality and the older woman. AB - Problems in defining, reporting, and sampling the sexual experience of older women have limited the available information. It should be remembered, however, that an aging population is a sign of societal success, not failure. To date, there has not been a better educated, healthier, wealthier, better-housed, or more self-sufficient generation of older women that at present. Working in the area of sexuality can help improve an important issue in the quality of life for the older woman. PMID- 8443743 TI - Loss of heterozygosity of p53 in oral cancers demonstrated by the polymerase chain reaction. AB - BACKGROUND: Alterations in the tumor suppressor gene p53 are the most frequently detected genetic abnormalities in human cancers. Inactivated tumor suppressor genes, including p53, often are suggested by loss of heterozygosity (LOH) studies. p53 gene inactivation has been reported in esophageal cancers. Because the etiologic factors for esophageal and intraoral carcinomas often are the same, corresponding molecular events may occur in oral squamous cell carcinoma (SCC) development. METHODS: The authors investigated LOH of the p53 gene in DNA from 27 primary oral cancers using a polymerase chain reaction (PCR)-based restriction fragment length polymorphism assay. DNA from fixed specimens of SCC and normal tissues was isolated and amplified at two p53 gene polymorphic restriction sites. RESULTS: In heterozygous individuals, 10 of 14 (71%) intraoral SCC demonstrated loss of p53 heterozygosity at one polymorphic restriction site. Two of five carcinomas showed LOH at a second site. CONCLUSIONS: These results suggest that inactivation of p53 is involved in the development or progression of SCC of the oral cavity. PMID- 8443744 TI - Lymph node metastasis in patients with adenocarcinoma of gastric cardia. AB - BACKGROUND AND METHODS: Prospectively, a consecutive series of 42 patients undergoing extended radical total gastrectomies (R 3/4 lymph node dissection) for adenocarcinoma of the gastric cardia from January 1988 to June 1991 were studied. The aims of this study were to evaluate the status of lymph node metastasis and the relationship between the frequency of nodal involvement and the extent of the primary tumor invasion. The Japanese criteria was used for postoperative staging. RESULTS: The incidence of operative morbidity and mortality in the series were 40.5% and 9.5%, respectively. Twenty-two (52%) of the patients had lymph node metastasis. For those patients, the most common sites of nodal involvement were the lesser curvature (72.7%), pericardiac (68.2%), left gastric artery (45.5%), left greater curvature (31.8%), splenic artery (31.8%), and the hilum (22.7%), inferior paraesophageal (18.2%), and diaphragmatic (18.2%) regions. Only one skip lymph node metastasis was discovered. In addition, no lymph node metastasis was found in the following areas: hepatoduodenal ligaments, mesenteric root, right paraadrenal, and subcardial lymph nodes. CONCLUSIONS: The study's results demonstrate that there seemed to a correlation among the status of lymph node metastasis, tumor size, and the depth of tumor invasion. However, the depth of tumor invasion appears to be a more important factor than tumor size in influencing the status of lymph node metastasis. The local recurrence rate was 2.4%. Consequently, the authors recommend that for the tumor with mucosal invasion only, a relatively conservative lymphadenectomy may be sufficient, but for tumors that invade beyond the mucosal region, radical lymphadenectomy may be helpful in preventing local recurrence. PMID- 8443745 TI - Isolation of Inoue-Melnick virus from colorectal carcinoma tissues. AB - BACKGROUND: Isolation of Inoue-Melnick virus (IMV) Type 1 from tumor tissues of patients with colorectal carcinoma in Japan was reported. A high prevalence of IMV antibodies has been found among patients with colorectal carcinoma in Buffalo, New York. METHODS: IMV was isolated from homogenates of colorectal carcinoma and other tissues, inoculated into MRC-5 human fibroblast cultures. IMV specific cytopathic effects were detected and titrated following 7 days of incubation in a roller-tube apparatus. RESULTS: IMV was isolated from all nine (100%) colorectal carcinoma tissues tested and all four (100%) normal parts of colon mucosa tissues obtained from patients with cancer. Biopsy specimens of normal colon mucosa from 10 patients without colon carcinoma were negative for IMV (0%). Average infectious titers of IMV in these tissue homogenates were 4.41 for tumor tissue and 2.55 log10 tissue culture infectious dose by 50% (TCID50)/0.1 ml for colon mucosa, respectively. Most of the isolates were the IMV intermediate type. CONCLUSIONS: Our results confirmed the production of infectious IMV in colorectal carcinoma tissues, as reported recently in Japan. The role of IMV in colorectal carcinogenesis is currently unknown. PMID- 8443746 TI - A pilot study of hepatic artery floxuridine combined with systemic 5-fluorouracil and leucovorin. A potential adjuvant program after resection of colorectal hepatic metastases. AB - BACKGROUND: Most patients with colorectal carcinoma metastatic to the liver have relapses after surgical resection of hepatic metastases with failures divided equally between hepatic and extrahepatic sites. A pilot study was begun using a regimen combining intrahepatic floxuridine (FUDR) and systemic 5-fluorouracil (5 FU) and leucovorin (LV) to determine its safety and efficacy. METHODS: Because this was a pilot study, 21 patients with unresectable hepatic metastases from colorectal carcinoma were treated to assess the regimen's toxicity. Eight patients had liver metastases that were resected completely; then they received treatment. FUDR was given by hepatic arterial pump through a 14-day continuous infusion at 0.25 mg/kg/day. Systemic therapy consisted of LV 200 mg/m2 and 5-FU 280 mg/m2 using a bolus dose of 5-FU for 5 days with escalation of the 5-FU dose in separate patient cohorts. The maximally tolerated 5-FU dose was 325 mg/m2. RESULTS: The median survival in the 21 unresectable patients was 16 months with a partial response rate of 56% (10 of 18 evaluable patients; 95% confidence interval, 38-79%). The major systemic toxicity was diarrhea, Grade 3 or 4, in 54% of patients being treated in the 4-week regimen and 19%, in the 5-week regimen. The level of hepatic toxicity was similar to that in previous studies using intrahepatic chemotherapy alone, i.e., 48% of patients had a 200% increase in alkaline phosphatase levels and 10% had bilirubin elevations of more than 3.0 mg/dl (one patient had documented biliary sclerosis). All eight patients treated with adjuvant therapy were alive without disease after a median follow-up of 23 months. CONCLUSIONS: Systemic 5-FU and LV can be combined safely with intraarterial FUDR without loss of efficacy or increased biliary toxicity. Eight patients treated with this regimen as adjuvant therapy after liver metastasis resection were alive and disease-free after a median follow-up of 23 months. PMID- 8443747 TI - Surgical lateral clearance in resected rectal carcinomas. A multivariate analysis of clinicopathologic features. AB - BACKGROUND: Incomplete removal of the tumor is the main cause of local recurrence in rectal carcinomas; this often occurs at the lateral aspects devoid of the peritoneum. The authors examined prospectively 80 resected rectal carcinoma specimens in an attempt to discover a reliable method to detect lateral resection margin (LRM) involvement by these tumors and to identify pathologic factors that would be prognostically important. METHODS: In each of the 80 resected specimens, the whole tumor was embedded, and whole-mount sections of the entire tumor and the surrounding mesorectum were examined after serial transverse slicing. The distance from the outermost part of the tumor to the LRM (surgical clearance) was measured. RESULTS: Six (7.5%) of the 80 specimens showed LRM involvement (defined as surgical clearance < or = 1 mm) in the single slice seen macroscopically to have the deepest tumor invasion, whereas 16 specimens (20%) were found to have LRM involved after examining all slices microscopically. Surgically clearance had a strong inverse relationship with Dukes staging (P < 0.001) and depth of tumor invasion (P = 0.001). The overall local recurrence rate was 28%; it was much higher (53%) in the patients who had LRM involved by tumor. As a whole, local recurrence was related significantly to LRM involvement (P = 0.006). Survival rates were correlated with macroscopic (n = 3) and microscopic (n = 13) features of the resected specimens using Cox multivariate regression analysis. Three of the nine pathologic parameters isolated (i.e., surgical clearance, cellular differentiation, and number of involved pericolic lymph nodes) were identified as favorable independent prognostic factors. CONCLUSIONS: Local recurrence is related closely to LRM involvement. Embedding and examining the entire tumor and mesorectum is the only reliable and satisfactory means of assessing LRM. Detailed pathologic study on the resected tumor is important when assessing the prognosis. PMID- 8443748 TI - Intraoperative high-dose rate interstitial irradiation of hepatic metastases from colorectal carcinoma. Results of a phase I-II trial. AB - BACKGROUND: Resection of liver metastases from colorectal carcinoma can be curative. Unresectable but liver-confined metastases might be ablated by high dose radiation with a similar curative result. METHODS: At Georgetown University Hospital, 22 patients with unresectable hepatic metastases from colorectal carcinoma underwent 24 interstitial irradiation procedures at laparotomy in a Phase I-II study. A single dose was administered with a high-dose rate iridium 192 afterloader. Dose to the tumor periphery was 20 Gy, 25 Gy, and 30 Gy in 13, 9, and 2 procedures, respectively. RESULTS: No acute or chronic radiation toxicity has occurred at a median follow-up of 11 months. Median actuarial local control at irradiated sites was 8 months, with 26% actuarial local control at 26 months by computed tomography (CT) or magnetic resonance imaging (MRI) scanning. In the two patients undergoing two procedures each, a second biopsy of previously irradiated areas demonstrated tumor eradication. CONCLUSIONS: This innovative, radical approach to unresectable colorectal hepatic metastases proved safe. Additional study is needed to determine whether interstitial irradiation is as effective as surgical resection, or whether it alters the natural history of the disease or longevity. PMID- 8443749 TI - Serum tumor markers CEA, CA 50, TATI, and NSE in lung cancer screening. AB - BACKGROUND: There are no effective means for screening for lung cancer, so the authors assessed the utility of four lung cancer tumor makers for screening. METHODS: A case-control study, nested in a cohort study based on the linkage of records of health survey examinees with Finnish Cancer Registry records, was used to test the validity of tumor markers carcinoembryonic antigen (CEA), tumor associated trypsin inhibitor (TATI), neuron-specific enolase (NSE), and CA 50 in lung cancer screening. Ten years after health examinations, record linkage indicated that 187 men had lung cancer; 344 control subjects, matched for age, sex, and municipality were drawn from the same records. RESULTS: The data allowed assessment of the sensitivity of the marker assays at a 95% specificity level, which was highest for CEA (17% at a concentration level of 5.3 micrograms/l). Logistic discrimination analysis indicated that of the other markers, only TATI, when used in combination, improved the discriminatory power of CEA. CEA and TATI levels correlated significantly with smoking. They also showed a significant gradient toward increasing risk of lung cancer from the lowest to the highest quintiles of marker levels (for CEA, crude relative risk between the highest and lowest quintiles, 8.6). The gradient also was evident in the subgroup whose cancer had been diagnosed more than 5 years after serum specimen collection. The trend persisted, although relative risk was halved after adjustment for smoking. CONCLUSIONS: The markers do not seem to be useful tools for lung cancer screening. However, CEA and TATI levels seem to give information on cancer risk long before the clinical cancer stage, as the quintile-based analyses of marker levels indicate. PMID- 8443750 TI - Treatment of myelodysplastic syndromes with daily oral idarubicin. A phase I-II study. AB - BACKGROUND: Idarubicin, a new anthracycline analogue, is available in an oral preparation, and responses have been observed using relatively aggressive therapy in patients with myelodysplastic syndromes (MDS). The authors studied whether a chronic low-dose schedule would be effective but less myelotoxic. METHODS: Forty two patients with MDS received daily low-dose oral idarubicin in 5-week courses that included 3 weeks of treatment, followed by a 2-week rest period. Doses were escalated when possible after the second course, and each patient was to receive six courses. RESULTS: Only one partial response was observed. Although no patient had fatal bone marrow toxicity, only eight patients received the full six courses, primarily because of myelosuppression. CONCLUSIONS: This schedule of oral idarubicin is relatively safe but produces fewer responses than are reported with the high-dose pulse regimens. PMID- 8443751 TI - Effects of lead time, length bias, and false-negative assurance on screening for breast cancer. AB - This article presents a model of breast cancer screening programs. The model shows the effects of the screening threshold, screen sensitivity, and false negative assurance on the cumulative mortality rate in the screened population. It shows that factors of screen design and a penalty associated with false negative assurance can result in excess mortality rates in screened populations- especially in those age classes in which the incidence of rapidly growing tumors is high. Factors related to the magnitude of this effect are described. PMID- 8443752 TI - A prospective study of the prognostic value of cathepsin D levels in breast cancer cytosol. AB - BACKGROUND: Cathepsin D is a lysosomal protease overexpressed and abnormally secreted in most breast cancer cells. Several retrospective clinical studies have shown that cathepsin D is an independent prognostic factor in breast cancer that is associated with a higher risk of recurrence and a shorter overall survival. METHODS: To the authors' knowledge, this is the first prospective study in which the prognostic value of cathepsin D was studied in 123 patients with primary breast cancer who were followed for 5 years between March 1985 and December 1990. Cathepsin D concentrations in breast cancer cytosol were measured using a solid phase sandwich immunoenzymatic assay. The most significant prognostic factors were identified by multivariate analysis using the Cox proportional-hazards method. RESULTS: The median value of cathepsin D was 20.8 pmol/mg of protein, which was approximately half than the median value found in subsequent assays done using a commercially available kit and reported in most retrospective studies. The cathepsin D status or level was correlated only with axillary lymph node involvement. A univariate analysis showed that high levels of cathepsin D (> 20 pmol/mg of protein) were correlated with a higher risk of recurrence and a shorter overall survival (P < 0.01 and P < 0.03, respectively). Using multivariate analysis, a high cathepsin D level, a negative progesterone receptor status, and lymph node involvement were the most important factors for predicting relapse-free survival (P = 0.02, P < 0.01, and P < 0.05, respectively). The cathepsin D level had prognostic value in patients with node-positive disease (P = 0.001) and appeared to be particularly useful in association with the progesterone receptor status by isolating a high-risk subgroup of patients (high cathepsin D level; negative progesterone receptor status). CONCLUSIONS: This first prospective study confirmed the prognostic value of the cathepsin D level in association with other major prognostic factors. The next step will be to determine whether the subset of patients with high cathepsin D levels would benefit from adjuvant therapy. PMID- 8443753 TI - Decelerating growth and human breast cancer. AB - BACKGROUND: Improved understanding of human breast cancer growth rates may have many clinical applications. Previous reports have used small numbers of patients and assumed an exponential growth rate. METHODS: The exponential equation and the most commonly used decelerating growth equations, the Gompertz equation and seven generalized forms of the logistic equation, were fitted to mammographic measurements of primary breast cancer using the least squares method. An average of 3.4 observations was made in 113 patients, whereas two measurements were made in another 335 patients. Tumors were assumed to originate as a single cell with the lethal tumor volume assumed to be 2(40) cells. RESULTS: All decelerating equations tested provided a better fit than the exponential, whereas a form of the logistic equation provided the best fit to the data. Limitations in the number of tumor measurements, the assumption of maximal tumor size, and biases inherent in the method of data collection are reviewed. These observations suggest families of curves that characterize breast cancer growth during the early period of clinical observation. CONCLUSIONS: Breast cancer growth in the early clinical period was modeled by a form of the logistic equation. The exponential equation fit the data least well. PMID- 8443754 TI - Mammographic assessment of human breast cancer growth and duration. AB - BACKGROUND: Accumulating data from numerous sources have confirmed that breast cancers have highly variable rates of growth. Contemporary thought supports that collectively the gross rates should decelerate with increasing tumor mass. METHODS: Using composite data derived from mammographically measured growth of breast cancers observed at the Universities of Heidelberg and Louisville, the growth curve providing the best fit to the observed data, and the variance occurring around this curve has been calculated. RESULTS: A generalized logistic equation provided the best fit, with a natural variance ranging from extremely rapidly growing to slowly growing cancer. These data do not cover the entire range of growth rates because cancers appearing acutely between mammograms were observed only once, and some breast cancers never grew. CONCLUSIONS: The highly variable decelerating growth rates of breast cancers are better but incompletely defined, and these rates are of value in considering screening strategies and prognosis. PMID- 8443755 TI - Patterns of presentation of Hodgkin disease. Implications for etiology and pathogenesis. AB - BACKGROUND: The etiology of Hodgkin disease remains uncertain. Patterns of presentation of Hodgkin disease are analyzed by histologic subtype with implications for etiology and pathogenesis. METHODS: The authors performed a detailed analysis of anatomic sites of involvement, histopathologic findings, and clinical features in 719 patients with Hodgkin disease who underwent staging laparotomy with splenectomy between April 1969 and December 1986. The presence of disease in each of 17 sites of potential nodal involvement was determined for each patient from a combination of clinical and surgical staging. Association among nodal sites was assessed in 2 x 2 tables by estimating the odds ratio and testing the significance with the chi-square test. A strict significance level (P = 0.01) was used. Log-linear models were used for assessing association in 2 x 2 tables while adjusting for other factors. RESULTS: The mediastinum, left side of neck, and right side of neck were the most common sites involved for patients with nodular sclerosing (NS) or mixed cellularity (MC) histologic subtypes. Each of these sites was involved 60% of the time. These sites were four or more times as common as other nodal sites above or below the diaphragm. In contrast, the mediastinum was involved in only 8% of patients with lymphocyte predominance (LP) histologic subtype. Significant associations were found between mediastinal disease and low cervical/supraclavicular lymph node disease, mediastinal disease and NS histologic subtypes, peripheral nodal disease and LP histologic subtypes, and between splenic disease and mixed cellularity/lymphocyte depletion (MC/LD) Hodgkin disease. The age at onset and sex of patients with Hodgkin disease and the patterns of nodal distribution were somewhat different for NS and MC/LD histologic subtypes. Even greater differences were seen between LP and other histologic subtypes. CONCLUSIONS: This study supports the conclusion that NS and MC Hodgkin disease spread by continguity, most often originating in the neck or mediastinum, and is consistent with evidence suggesting an infectious agent in the pathogenesis of these subtypes of Hodgkin disease. In contrast, LP Hodgkin disease is characterized by different sites of presentation and patterns of spread. This suggests that two or perhaps three clinicopathologic subtypes of Hodgkin disease exist. Implications for etiology and pathogenesis are discussed. PMID- 8443756 TI - Pilot study of ambulatory infusional ifosfamide admixed with carboplatin. AB - BACKGROUND: Ifosfamide and carboplatin are agents that have completed Phase I studies using a continuous infusion schedule for as long as 14 days. The in vitro compatibility of the two drugs allows for the simultaneous administration in an admixture, and a pilot study was undertaken to determine the feasibility and tolerability of the infusion schedule for the combination. METHODS: Ifosfamide at 500 mg/M2/day and carboplatin at 15 or 20 mg/M2/day were administered for 14-day cycles repeated at 28 days in 29 patients, with a total of 60 courses administered. RESULTS: Total cumulative dose per cycle was: ifosfamide 7.0 g/M2 and carboplatin 210-280 mg/M2. Hematuria developed in five patients, four of whom had prior urologic disease, severe thrombocytopenia, or pelvic radiation. In all patients, the hematuria was transient and inconsequential despite the absence of mesna. Grade 3 or 4 leukopenia was observed in eight patients with or without thrombocytopenia and delayed subsequent treatment cycles. Thrombocytopenia was less frequent (Grade 3, 2 patients: Grade 4, 1 patient). No significant episodes of sepsis or hemorrhage were noted. Anemia requiring transfusion developed in 12 of 29 patients. Twenty-one of the 29 patients had received prior chemotherapy. Five of seven previously untreated patients with non-small cell lung cancer achieved a complete (1) or partial (4) response. CONCLUSIONS: A continuous 14-day infusion of ifosfamide admixed with carboplatin is feasible in an ambulatory setting with no need for adding mesna for urologic protection and full dosage administration for each agent. Phase 2 studies in non-small cell lung cancer would be reasonable at the optimal doses of ifosfamide 500 mg/M2/day and carboplatin 15 mg/M2/day, and the potential exists for the introduction of additional agents, such as etoposide. PMID- 8443757 TI - In vitro modulatory effects of interleukin-3 on macrophage activation induced by interleukin-2. AB - BACKGROUND: The concomitant activation of macrophage-mediated immunosuppressive events might represent one of the most important biologic factors responsible for the decreased efficacy of cancer immunotherapies, including that of interleukin (IL)-2. In previous studies, the authors observed that the increase in the soluble IL-2 receptor (SIL-2R) and neopterin levels was related to the generation of macrophage-mediated immunosuppression and associated with a reduced clinical efficacy during IL-2 cancer immunotherapy. Because both cytokines and neurohormones may influence the macrophage system, the current study was done to evaluate the effects of IL-3 and of the pineal hormone melatonin (MLT) on monocyte response to IL-2 administration. METHODS: Peripheral blood monocytes were incubated with different concentrations of IL-2, IL-3, and MLT, either alone or in association. RESULTS: SIL-2R, neopterin, and tumor necrosis factor-alpha mean concentrations in the medium significantly increased during incubation with IL-2 at a concentration of 100 Cetus units/ml. IL-3 alone, at a dose of 10 ng/ml, also stimulated tumor necrosis factor release; no effect was found on SIL-2R and neopterin. The IL-2-induced neopterin rise was blocked by a concomitant incubation with IL-3 at a dose of 10 ng/ml. Finally, the concomitant incubation with IL-3 and MLT further inhibited neopterin release and significantly decreased IL-2-induced SIL-2R secretion. CONCLUSIONS: These results suggest that IL-3 alone or in association with MLT may modulate macrophage functions during cancer immunotherapy with IL-2 and decrease the IL-2-induced macrophage activation. PMID- 8443758 TI - Clinical evaluation of tumor targeting with a high-affinity, anticarcinoembryonic antigen-specific, murine monoclonal antibody, MN-14. AB - BACKGROUND: The authors previously reported that an anticarcinoembryonic antigen antibody against a carcinoembryonic antigen (CEA)-specific epitope is preferred for clinical investigations. They developed a second generation, CEA-specific murine monoclonal antibody (MoAb), MN-14 (IMMU-14), that has a tenfold higher affinity. This report summarizes the initial clinical experience with the new MoAb. METHODS: MN-14 immunoglobulin G (IgG) (0.5-6.0 mg) was labeled with radioactive iodine (I131) (5-80 mCi) and injected into 22 patients with cancer. External scintigraphy was used to determine targeting in patients with low and highly elevated plasma CEA. Quantitative external scintigraphy methods were used to determine organ and tumor clearance rates and absorbed radiation doses. Targeting data were correlated with several factors, including MoAb protein dose, plasma CEA, and relative tumor burden. RESULTS: Despite more than 80% complexation with plasma CEA of more than 500 ng/ml, all known tumor sites were disclosed by external scintigraphy. The overall sensitivity of tumor targeting on a lesion basis was 89%. The residence time in the blood was predicted by body weight (P = 0.05) and the log of plasma CEA (P = 0.043). The absorbed dose to the red marrow and total body could be predicted by the body weight of the patient, but no other factor contributed significantly to the clearance rate or absorbed dose to the organs. Individual tumors received an average dose of 9.3 +/- 6.4 cGy/mCi. The absorbed dose to the tumors was negatively correlated to the weight of the tumor, and the percent uptake in the tumor was positively correlated to the estimated total tumor burden. Patients injected with approximately 5 mg of MN 14 IgG were more likely to have anti-mouse antibodies (HAMA) develop than were patients who were injected with less MoAb. CONCLUSIONS: These results suggest that MN-14 targets tumors effectively, even in the presence of elevated circulating CEA. Additional studies are necessary to determine if an advantage for the higher affinity MN-14 MoAb, compared with the lower affinity NP-4 MoAb, can be appreciated clinically. PMID- 8443759 TI - Cranial computed tomography in children with acute lymphoblastic leukemia after prophylactic treatment with cranial radiation therapy and intrathecal methotrexate. AB - BACKGROUND AND METHODS: Thirty-one children with acute lymphoblastic leukemia (ALL) who had received cranial radiation therapy (CrRT) and five concomitant doses of intrathecal methotrexate (IT MTX) for central nervous system prophylaxis (CNSP) and who had an event-free survival exceeding 5 years had cranial computed tomography (Cr CT) examination. The fractional dose for 21 of them was 1.5 Gy. The interval between the completion of CNSP and the time of Cr CT ranged from 5 to 8.5 years, with a median of 5 years 2 months. RESULTS: Unlike the previous reports in the literature that 9-77% of children with ALL who had received Cr RT 18 Gy and IT MTX as CNSP had CT scan abnormalities, in this study no patient had CT scan abnormalities. CONCLUSIONS: Our results might be attributable to the fractional dose of Cr RT being adequate, the IT chemotherapy being suitable, and the systemic chemotherapy not being intensive. PMID- 8443760 TI - Ewing sarcoma of bone in infants and toddlers. A clinicopathologic report from the Intergroup Ewing's Study. AB - BACKGROUND: Nineteen patients with Ewing sarcoma of bone, each younger than 3 years of age at the time of initial presentation, are reported. These children represent an unusually young age group for documented Ewing sarcoma and represent 2.6% of all patients registered in the Intergroup Ewing's Sarcoma Study (IESS). METHODS: The diagnosis was made on combined histologic, clinical, and radiographic grounds and was supported by immunohistochemistry in nine patients and electron microscopic study in eight patients. Immunohistochemical studies showed no staining against neuro-specific enolase, chromogranin, or S-100 in any patients, and in only one in nine patients were results of such studies focally positive against Leu-7. RESULTS: The most marked clinical variation between this group of infants and the general IESS patient population was a striking predominance of female patients in the younger age group (P < 0.001). There was a trend toward more rib, pelvis, and proximal long bone tumors in the infants and toddlers. The overall survival rate of the infants was 56%, almost identical to the survival rates of the older children. All of the infants who died of disease did so within 4 years. Extended follow-up as long as 9.9 years has found no late deaths attributable to tumor. The most significant late complications of therapy included cardiotoxicity with cerebral embolization from the heart and a short lower limb secondary to radiation therapy. CONCLUSIONS: Ewing sarcoma must be considered in the differential diagnosis of small cell, round cell, and blue cell tumors in bone, even in infants and toddlers. PMID- 8443761 TI - A phase II trial of ifosfamide in previously untreated children and adolescents with unresectable rhabdomyosarcoma. AB - BACKGROUND: Children and adolescents with unresectable rhabdomyosarcoma fare poorly when treated with contemporary chemotherapeutic regimens. Evaluation of newly developed agents in these patients is important to improve their outcome. Based on a preclinical rhabdomyosarcoma xenograft model that accurately predicted the activity of new agents, the safety and efficacy of ifosfamide was evaluated as part of a Phase II clinical trial in previously untreated children with unresectable rhabdomyosarcoma. METHODS: Twenty-two children and adolescents (median age, 9 years) with newly diagnosed unresectable rhabdomyosarcoma (Intergroup Rhabdomyosarcoma Study Group III [n = 15] or IV [n = 7]) received two courses of ifosfamide at a dose of 1.6 g/m2 intravenously for 5 days over a 6 week period. Then the patients were evaluated for response, and additional treatment with surgery, radiation therapy, and multiagent chemotherapy (vincristine, cyclophosphamide, dactinomycin, and doxorubicin) was administered. RESULTS: Nineteen of 22 patients (86%) had a partial response to ifosfamide given as a single agent. No complete responses to this agent alone were observed. After administration of additional chemotherapy and local control measures (radiation therapy and surgery), the estimated proportion of patients surviving progression free at 2 years was 63% (95% confidence interval, 37-80%). Ifosfamide was tolerated well; the most frequent toxicity was nondose-limiting myelosuppression. Transient mild renal toxicity infrequently was observed, and no central nervous system toxicity occurred in this group of patients. CONCLUSIONS: Ifosfamide appears to have significant clinical activity in untreated patients with unresectable rhabdomyosarcomas. These findings provide an accurate estimate of the response rate to single-agent ifosfamide in this group of previously untreated patients and thus provide a foundation for its rational incorporation into multiagent clinical trials. In addition, the potential benefits of this type of new drug development were demonstrated. PMID- 8443762 TI - Risk factors for breast cancer development. PMID- 8443763 TI - Pathologic findings from the National Surgical Adjuvant Breast Project (Protocol 4). Discriminants for 15-year survival. National Surgical Adjuvant Breast and Bowel Project Investigators. AB - Twenty-one pathologic and five clinical features of Stage I and II invasive breast cancers from 620 patients enrolled in National Surgical Adjuvant Breast Project Protocol B-04 were analyzed to determine their predictive value for 15 year survival. Ten pathologic features had a statistically significant univariate prognostic relationship with long-term survival. These were analyzed further using a Cox regression model that found only the number of nodal metastases (0, 1 3, 4-9, or 10+), tumor size (< or = 2.0 cm versus 2.1-4 and 4.1 + cm), and the presence or absence of nipple involvement to be significant independent prognostic discriminants. Combinations of these three characteristics modestly increased their individual prognostic value. Differences in the findings in this study from those observed in the same patient population at 5 and 10 postoperative years and their relationship to other markers detected by ancillary pathologic techniques briefly are discussed. PMID- 8443764 TI - Flow cytometric (DNA content and S-phase fraction) analysis of breast cancer. AB - The advent of therapeutic alternatives for patients with breast cancer has altered their clinical management profoundly. Because of this, the need for reliable prognostic indicators with definable clinical utility has spawned a number of objective evaluations of the neoplasm itself. Flow cytometric analysis of DNA and the cell cycle (S-phase fraction) are two of the objective measurements. Their current status in breast cancer is unclear. In the important category of carcinomas with negative axillary lymph nodes, DNA content (ploidy) information does not add important, independent, or prognostic information. S phase fraction, in addition to correlating with DNA content and histologic grade, may be an independent factor, but methodologic variables have hampered definite conclusions about its utility. Currently, given the rather consistent absence of correlation between DNA ploidy, S-phase fractions, and nodal metastases, the independent prognostic utility of the two flow cytometric parameters can be questioned. A resolution of their final status in the prognostic hierarchy depends on rigorous adherence to the variables affecting them, i.e., preanalytic, analytic, and postanalytic factors. PMID- 8443765 TI - On the possible role of involution in the natural history of breast cancer. AB - Although the importance of the relationship between age and cancer incidence rates is recognized universally, little attention seems to have been paid to the relationship between the physiologic aging process in the breast and breast cancer risk. The natural history of breast cancer was examined in the context of involution of the breast, and it was proposed that the rate and extent of involution might be important determinants of breast cancer risk. It was concluded that additional studies to characterize the process of involution better histopathologically and to examine the associations between the rate and extent of involution and breast cancer risk are warranted. PMID- 8443766 TI - How to integrate steroid hormone receptor, flow cytometric, and other prognostic information in regard to primary breast cancer. AB - A large group of patients with node-positive breast cancer was divided into a training set (n = 851) and a validation set (n = 432) to demonstrate techniques for integrating steroid hormone receptor status, DNA flow cytometric findings, and other prognostic factors to predict patient survival. Multivariate analyses showed that estrogen receptor status, the number of involved axillary lymph nodes, patient age, S-phase fraction, progesterone receptor status, and tumor size were significant predictors of survival in patients with node-positive breast cancer. Techniques for optimizing and validating a cut point for a new prognostic factor and for examining alternative representations of prognostic factors were demonstrated. Prognostic indexes were created that could be used to identify patients with very good or very poor prognoses. PMID- 8443767 TI - Prognostic factors observed in current clinical trials. AB - Adjuvant therapy of breast cancer has evolved over the past 15 years from an interesting clinical experiment to the standard of care for many patients. The toxicities of different treatments vary from those with minimal side effects, such as tamoxifen, to those with potentially life-threatening side effects. Current clinical trials are evaluating increasingly higher risk treatments, such as high-dose chemotherapy autologous bone marrow rescue. Chemotherapy is being used in groups that have previously been treated only with hormonal interventions or who have received no adjuvant therapy. The delineation of risk, such that the risks of treatment can be closely tied to the risk of recurrence is thus a desirable goal for clinical-laboratory research. Prognostic factors identified in treated patients, however, may be measures of treatment resistance versus treatment sensitivity rather than some underlying biologic characteristic defining a tumor's malignant potential. PMID- 8443769 TI - Continuity of care ... the birth centre experience. PMID- 8443768 TI - Estrogen-replacement therapy after breast cancer. Risks versus benefits. AB - In the current aging society, more than 30 million women have an average postmenopausal life expectancy of 28 years. Coronary heart disease is the leading cause of death in older women, and osteoporosis results in an estimated 1.5 million fractures per year. Various studies have suggested that postmenopausal estrogen-replacement therapy could reduce the morbidity and mortality associated with these conditions. Based on the results of several "natural experiments," it was proposed that estrogen-replacement therapy should be considered for menopausal women who have been treated successfully for breast cancer. The benefits and risks of estrogen-replacement therapy are reviewed, and recommendations for management and future research are suggested. PMID- 8443770 TI - Staff nurse satisfaction. PMID- 8443772 TI - Midwife-friendly care. PMID- 8443771 TI - [Professional burnout]. PMID- 8443773 TI - Breastfeeding, A to Z. PMID- 8443774 TI - Breastfeeding the sleepy infant. PMID- 8443775 TI - Kids and car seats. PMID- 8443776 TI - Career planning. PMID- 8443777 TI - Sexual contact between nurses and patients. PMID- 8443778 TI - Strategies for staff development. PMID- 8443779 TI - Changing the model of practice: geriatric long term care in an acute care hospital. PMID- 8443780 TI - Competencies. The foundation for future nursing exams. PMID- 8443781 TI - [Music therapy]. AB - Music stands for the mystical expression of life cycles celebrations: birth, death, renewal of seasons, hunting, rituals of passage... It serves in other familiar conjunctures, such as the dentist chair, waiting rooms and on the telephone, helping us to relax or increase our patience. However, music is not for everyone at all times. With each individual, its significance varies according to the moment and the situation. If a nurse can make use of it with some persons, it is because they have convinced her that music can be of comfort to them and can reduce their pain and anxiety. The role of the caregiver is to attend to the sick by different means. Music is one of them. By being alert and prudent, nurses can provide a care traditionally perpetuated as comforting. Music therapy is the controlled use of music and its elements to help the physiological, psychological and emotional integration of the individual in the course of a treatment for illness or incapacity. Its active mode implies that clients participate by playing an instrument or by singing to express oneself. It opens or maintains the field of communication. In the passive mode, therapists use tapes, disks or interpret pieces of music themselves. Its meaning, its power, take on other dimensions. When introducing music on a palliative care unit, for example, an initial assessment of each client is required to discover and monitor the degree of their acceptance. Thereafter, a continuous evaluation ensures that appropriate adjustments are made in the choice of music offered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8443782 TI - Modulatory influence of sandalwood oil on mouse hepatic glutathione S-transferase activity and acid soluble sulphydryl level. AB - The effect of the oil from the wood of Santalum album on glutathione S transferase (GST) activity and acid soluble sulphydryl (SH) levels in the liver of adult male Swiss albino mice was investigated. Oral feeding by gavage to mice each day with 5 and 15 microliters sandalwood oil for 10 and 20 days exhibited an increase in GST activity in time- and dose-responsive manners. Feeding a dose of 5 microliters sandalwood oil for 10 and 20 days caused, respectively, a 1.80-fold (P < 0.001) and 1.93-fold (P < 0.001) increase in GST enzyme activity, while feeding a dose of 15 microliters of the oil per day for 10 and 20 days induced, respectively, 4.73-fold (P < 0.001) and 6.10-fold (P < 0.001) increases in the enzyme's activity. In addition, there were 1.59-fold (P < 0.001) and 1.57 (P < 0.001) increases in acid-soluble SH levels in the hepatic tissue of the mice following feeding of the oil at the dose levels of 5 and 15 microliters for 10 days. Furthermore, mice fed on a diet containing 1% 2(3)-butyl-4-hydroxyanisole (positive control) also showed an increase in hepatic GST activity and SH levels. Enhancement of GST activity and acid-soluble SH levels are suggestive of a possible chemopreventive action of sandalwood oil on carcinogenesis through a blocking mechanism. PMID- 8443783 TI - Inhibitory effect of the non-steroidal anti-inflammatory drugs, indomethacin and piroxicam on 2-acetylaminofluorene-induced hepatocarcinogenesis in male ACI/N rats. AB - The modifying effects of the non-steroidal anti-inflammatory drugs, indomethacin (IMC) and piroxicam (PC) on hepatocarcinogenesis induced by 2-acetylaminofluorene (AAF) were investigated in male ACI/N rats. Rats were divided into 6 groups: group 1 was fed a diet containing 200 ppm AAF for 16 weeks, starting at 6 weeks of age; group 2 was fed an AAF together with 130 ppm PC-containing diet; group 3 received an AAF diet and IMC (10 ppm) in their drinking water; group 4 was fed a PC diet alone; group 5 was given IMC alone; and group 6 served as controls. The PC diet, or the drinking water containing IMC, was given to the rats starting at 5 weeks of age until 1 week after the carcinogen exposure. At termination of the experiment (week 36), the incidences of iron-excluding altered liver cell foci (24.2 +/- 5.2/cm2) and liver cell tumors (1/10, 10%), and the tumor multiplicity (0.10/rat) in rats of group 2 were significantly smaller than those of group 1 (foci incidence, 42.6 +/- 6.7/cm2; tumor incidence, 10/10, 100%; and multiplicity, 4.00/rat) (P < 0.05). Similarly, the incidence of iron-excluding hepatocellular foci (27.4 < 1.2/cm2) and liver cell tumors (1/10, 10%) and the tumor multiplicity (0.10/rat) in rats of group 3 were significantly lower than those of group 1 (P < 0.05). There were no liver cell lesions (foci and neoplasms) in rats of groups 4, 5 and 6. Thus, PC and IMC inhibited the hepatocarcinogenesis induced by AAF when administered concurrently with the carcinogen and the results may indicate possible involvement of altered arachidonic metabolism in the initiation phase of AAF-induced liver carcinogenesis. PMID- 8443784 TI - Expression of plasminogen activator and plasminogen activator inhibitor by rat mesothelioma induced by asbestos. AB - We have investigated the expression of plasminogen activators (PAs) and PA inhibitors (PAIs) by an asbestos-induced mesothelioma. Using zymographic, immunological and biochemical techniques it was demonstrated that cell lines derived from the tumor express high levels of PAI and low levels of a UK-like PA. Adherent and partially non-adherent variants of the mesothelioma expressed indistinguishable amounts of PAI and UK. Based on partial biochemical characterization, the PAI secreted by the mesothelioma cells was a set of PAIs which consisted of PAI-1 in addition to other species. These observations indicate that the difference in growth phenotype of the adherent and partially non-adherent lines was not due to detectable differences in PA and PAI expression. PMID- 8443785 TI - Expression of cathepsin D in malignant and in the corresponding non-malignant node-negative laryngeal samples: correlation with receptors for androgen, glucocorticoid, oestrogen and progesterone. AB - A standard immunoradiometric technique was used to investigate the distribution of the intracellular aspartic proteinase cathepsin D in 33 malignant and in the corresponding histologically-proven non-malignant fragments obtained from lymph node negative patients suffering from larynx cancer. In both tissues the androgen, glucocorticoid, oestrogen and progesterone receptors were also assayed. Our data indicate that cathepsin D was present in both tissues, with level significantly higher (P < 0.0001) in the cancerous fragments (with a mean of 33 +/- 3.4 pmol/mg protein) than in the corresponding non-cancerous specimen (with a mean of 20.8 +/- 2 pmol/mg protein). A significant positive association (P < 0.001) between cathepsin D and PR concentration values in the cancerous larynx was observed; accordingly, tumours expressing PR had significantly (P = 0.0005) higher cathepsin D levels than the tumours which did not contain the receptor. In contrast, such a relationship was absent in the non-malignant specimens. As regards the other steroid receptors, no significant relationship between them and cathepsin D was observed. We conclude that cathepsin D may have a role also in laryngeal carcinoma and that its association with the PR could indicate a possible role of the receptor in the biology of this disease. PMID- 8443787 TI - Selective toxicity in putative preneoplastic hepatocytes: a comparison of hydroquinone and duroquinone. AB - In this paper data is presented suggesting selective toxicity towards enzyme altered hepatocytes. Hydroquinone (HQ) treatment 24 or 48 h after diethylnitrosamine (DEN) initiation reduced the number of glutathione S transferase-P (GST-P)-positive hepatocytes in situ. Furthermore, in experiments on primary cultures of hepatocytes from control rats a synergism in cell killing between DEN and HQ was observed. In another in vitro system the effect of HQ and duroquinone (DQ) on GGT-positive and -negative hepatocytes was investigated. DQ was shown to affect the GGT-positive cells, while HQ mainly affected GGT-negative cells. These results suggest that HQ can reduce the population of enzyme altered foci (EAF) precursor cells by synergistic interactions with DEN, but provide no support for the notion that HQ selectively damage cells in developed EAF. This conclusion is supported by previously published data on effects of HQ on the development of EAF. PMID- 8443786 TI - Receptors for tumor-promoting phorbol esters in rat ventral prostate. AB - The presence of tumor-promoting phorbol ester receptors in rat prostate was investigated by studying the binding of phorbol diester 12,13-dibutyrate (PDBu) in both soluble and particulate subcellular fractions. Binding of [3H]PDBu to the soluble fraction was optimal after the addition of phosphatidylserine (0.1 mg/ml) and Ca2+ (1 mM). Both subcellular fractions exhibited a single class of PDBu receptor (Kd between 97 and 128 nM) as shown by saturation binding experiments. Phorbol esters with tumor-promoting activity showed a higher affinity for these receptors than did endogenous ligands such as diacylglycerols whereas phorbol esters without tumor-promoting activity were ineffective even at concentrations as high as 1 microM. These properties are highly representative of protein kinase C activity. PMID- 8443788 TI - Inhibitory effects of fucoxanthin, a natural carotenoid, on N-ethyl-N'-nitro-N nitrosoguanidine-induced mouse duodenal carcinogenesis. AB - Fucoxanthin was shown to inhibit chemical carcinogenesis. Fucoxanthin is a natural carotenoid prepared from brown algae which is an ingredient used daily in Japanese food. In this study, all mice were given 0.01% N-ethyl-N'-nitro-N nitrosoguanidine in their drinking water for 4 weeks. This was followed by 0.005% fucoxanthin in dimethylsulfoxide or the vehicle alone in the drinking water. In the 16-week fucoxanthin-treated group both the percentage of tumor-bearing mice and the average number of tumors per mouse were significantly lower than those of the control group. The results indicate that fucoxanthin inhibited duodenal carcinogenesis induced by N-ethyl-N'-nitro-N-nitrosoguanidine in mice. PMID- 8443789 TI - O6-alkyltransferase activity in normal and abnormal gastric mucosa. AB - The activity of the DNA repair enzyme O6-alkyltransferase has been studied in a series of stomachs with abnormal gastric mucosa and the activities found compared with those in normal stomachs. Enzyme activities found in stomachs with the macroscopic abnormalities of gastric ulcer, duodenal ulcer or gastric cancer were not significantly different from normal. In those stomachs where there was histological evidence of chronic atrophic gastritis or intestinal metaplasia however enzyme activities (mean 398 fmole/mg) were significantly higher than normal (mean activity 228 fmole/mg activity P < 0.001). We speculate that the conditions which stimulate these histological changes also give rise to induction of O6-alkyltransferase. PMID- 8443790 TI - Glutathione-S-transferase, alcohol dehydrogenase and aldehyde reductase activities during diethylnitrosamine-carcinogenesis in rat liver. AB - Several enzymes metabolize the toxic aldehydes produced during lipid peroxidation, such as 4-hydroxynonenal. During carcinogenesis induced by diethylnitrosamine in rat liver, an increase in aldehyde dehydrogenase, in comparison with normal liver, has already been shown. This paper demonstrates that, although to a lesser extent than aldehyde dehydrogenase, aldehyde reductase and glutathione-S-transferase also increase during carcinogenesis. Of the latter two enzymes, aldehyde reductase increases more markedly in a progressive fashion during the months of development of nodules and hepatoma. The increase of enzymes able to metabolize 4-hydroxynonenal, as well as other aldehydes, is certainly important in protecting tumour cells against cytotoxic effect of aldehydes. PMID- 8443791 TI - Studies on acute myelomonocytic leukemia in LBF1 rats. AB - Granulocytic leukemia was induced in Long-Evans (LE) rats by using the Huggins and Sugiyama method. After serial passage the cells became transformed. The newly transformed cells could be transplanted to LBF1 hybrid rats and observed more readily. A quantity of 10(8) cells/100 g body weight was injected intravenously and after 2-3 weeks myelomonocytic leukemia developed. By examining the bone marrow, spleen and lymph nodes, cytochemical tests verified this transformation. Transplanting 10(2)-10(4) cells under the renal capsule, a quickly growing solid tumor was observed, which caused metastasis to the parathymical lymph nodes and peritoneum. The investigation of oncogene expression for the myc and ras families revealed the presence of myc p62 and ras p21 oncoproteins in the tumor cells by using monoclonal antibodies in immunohistochemical tests. LBF1 rats proved to be good models in obtaining solid tumor growth and myelomonocytic leukemias, equivalent to human M4-M5 type leukemia. PMID- 8443792 TI - Diethylstilbestrol liver carcinogenicity and modification of DNA in rats. AB - Administration of diethylstilbestrol to female Sprague-Dawley rats at 10 mg/kg body weight daily by gavage for 1 year induced liver adenomas and carcinomas and pituitary adenomas. Using the 32P-postlabeling assay for DNA alterations, at 24 h after administration of a single dose of 100 mg/kg, modified bases were found. PMID- 8443793 TI - Incorporation of arachidonic acid in a human cancer gastric tumor cell line (HGT) at various stages of cell proliferation. AB - Human cancer gastric cells (HGT) in culture were labeled with [14C]arachidonic acid. The kinetic of acylation of arachidonic acid was similar using cells after 3, 5 and 7 days of culture. However, the duration of the proliferation enhanced the acyltransfer to triglycerides and inhibited the transfer to phospholipids. After 8 h of incubation with [14C]arachidonic acid the radioactivity was predominantly recovered in the phosphatidylcholine and phosphatidylethanolamine species. Prelabeling-chase experiments indicated a preferential incorporation of arachidonic acid into phosphatidylcholine followed by a transfer of arachidonate to phosphatidylethanolamine. PMID- 8443794 TI - Effects of medium conditioned by retinal pigmented epithelial cells on neurotransmitter phenotype in retinoblastoma cells. AB - We previously reported that medium conditioned by retinal pigmented epithelial cells can induce cellular differentiation in human retinoblastoma cells. Extensive neurite outgrowth, increased expression of neuronal marker molecules and decreases expression of glial marker molecules are characteristic of the differentiated phenotype. In the studies described here, we examine whether modulations in the expression of potential neurotransmitter molecules, catecholamines and indolealkyl amines, might be associated with the differentiation of retinoblastoma cells. Concentrations of serotonin, 5 hydroxyindoleacetic acid, 3-methoxytyrosine, homovanillic acid, and 3-methoxy-4 hydroxyphenylacetic acid in extracts of differentiated and undifferentiated retinoblastoma cells were assessed by HPLC. The results show that serotonin and its metabolite, 5-hydroxyindoleacetic acid, are characteristically present in undifferentiated cells. Dopa metabolites, 3-methoxytyrosine, homovanillic acid and 3-methoxy-4-hydroxy-phenylacetic acid, are uniquely present in differentiated cells. It appears that differentiation of retinoblastoma cells induced by factors secreted by retinal pigmented epithelial cells involves a switch from a serotonergic phenotype to one dominated by metabolites of dopa. These findings may provide clues about the factors that control retinoblastoma cells and metastasis. PMID- 8443795 TI - Hepatocarcinogenic potency of mixed and pure enantiomers of trans-7,8 dihydrobenzo[a]pyrene-7,8-diol in trout. AB - The hepatocarcinogenic potency of pure and racemic trans-7,8 dihydrobenzo[a]pyrene-7,8-diol was investigated in embryos and sac-fry rainbow trout. Embryos microinjected with (+/-)-trans-7,8-dihydrobenzo[a]pyrene-7,8-diol ((+/-) BP-7,8-DHD) developed liver tumors 9 months after hatching. However, this exposure protocol resulted in high mortalities. Microinjection of newly hatched sac-fry with 0.01-1.0 microgram of (+/-) BP-7,8-DHD resulted in a dose-dependent production of liver tumors (0-13%) similar to the results with embryos but without the problem of high mortalities. Co-injection of sac-fry with (+/-) BP 7,8-DHD and either beta-naphthoflavone or carbon tetrachloride significantly enhanced the tumor response (approx. 3-fold). The relative carcinogenic potencies of the pure (+) and (-) enantiomers of BP-7,8-DHD were evaluated by microinjection into sac-fry at doses of 0.5-5.0 micrograms. The results demonstrated that the (-) enantiomer was 4-18 times more potent than the (+). Mixed carcinomas were the most prevalent liver tumors observed. These results demonstrate that trout embryos and sac-fry are both responsive to hepatocarcinogenesis initiation by injection with BP-7,8-DHD. The marked enhancement seen with co-injection of sac-fry with beta-naphthoflavone or carbon tetrachloride suggests that both cytochrome P-450-dependent and lipid peroxidation-dependent pathways could be involved in bioactivation of this compound, presumably through epoxidation at the 9,10-position. As is the case with mammals, the (-) enantiomer of BP-7,8-DHD is a more potent carcinogen than the (+) enantiomer. PMID- 8443796 TI - Inhibitory effects of tea extracts and (-)-epigallocatechin gallate on DNA synthesis and proliferation of hepatoma and erythroleukemia cells. AB - Polyphenols extracted from green or black tea with ethyl acetate were strongly inhibitory for DNA synthesis in HTC rat hepatoma cells and DS19 mouse erythroleukemia cells at concentrations of 0.1-0.2 mg/ml. There was less inhibition with a subsequent black tea fraction extracted with butanol and with the residual water-soluble fraction. Although cell proliferation was inhibited by (-)-epigallocatechin gallate and the tea extracts, there were only marginal effects on differentiation of DS19 cells as judged by hemoglobin synthesis. PMID- 8443797 TI - Deregulated c-fos augments cell proliferation of B cells mediated by lipopolysaccharide. AB - We have examined effects of the deregulated c-fos protein on the lipopolysaccharide (LPS)-mediated B cell responses using splenic B cells from transgenic lines carrying the mouse c-fos gene under the control of the H-2K (H2 c-fos) and the inducible Mx promoter (Mx-c-fosD). High c-fos expression was induced in Mx-c-fosD B cells by LPS stimulation. DNA synthesis of the B cells from both lines was augmented depending on the amount of exogenous c-fos. This augmentation resulted in the increase of IgM and IgG2b productions in the culture. These results suggest a functional role of c-fos protein in cell cycle progression of the activated B cells. PMID- 8443798 TI - The effect of antisense p120 construct on p120 expression and cell proliferation in human breast cancer MCF-7 cells. AB - Malignant transformation of NIH3T3 cells was observed by transfection with the pSVX vector containing a sense human p120 cDNA construct (pSVX120). Subsequent transfection of these transformed cells with a dexamethasone inducible antisense p120 construct (pMSG021) markedly reduced the expression of human p120 and the growth rate of these transformed cells (Perklaky et al., Cancer Res., (1992) 52, 428-436). In the present study, a human breast cancer cell line (MCF-7) which expresses the p120 protein was transfected by electroporation with a pSVX plasmid construct containing the antisense p120 cDNA (pSVX021). Clones containing the pSVX021 construct were selected and analyzed for expression of p120 mRNA, protein and growth characteristics. The expression of the p120 protein was inhibited by 44% in the antisense-transfected MCF-7pSVX021 cells; a 56% inhibition of cell growth and a reduced colony formation in soft agarose were also observed. The growth of MCF-7 cells transfected with the p120 antisense construct was reduced by 93% in nude mice. PMID- 8443799 TI - Persistent inhibition of DNA synthesis in irradiated rat embryo fibroblasts expressing the oncogenes H-ras plus v-myc derives from inhibition of replicon initiation and is mitigated by staurosporine. AB - We have previously shown that rat embryo fibroblasts expressing the oncogenes H ras plus v-myc experience a prolonged inhibition of DNA replication after exposure to ionizing radiation as compared to normal rat embryo fibroblasts, or rat embryo fibroblasts expressing H-ras or v-myc alone. Here we show that this enhanced inhibition of DNA replication in cells expressing H-ras plus v-myc is due to inhibition of the main controlling event of DNA replication, i.e., replicon initiation, that this inhibition is reversible, and that the expression of this phenotype is reverted by staurosporine, a protein kinase inhibitor. These findings implicate genetic influences in the processes that control DNA replication in irradiated cells and identify events in the regulation of DNA replication that become apparent several hours after irradiation. The products of the oncogenes H-ras and v-myc appear to be members of, or exert influence on, this controlling pathway. PMID- 8443800 TI - Heterotransplantation of early B-lineage acute lymphoblastic leukemia using a solubilized attachment matrix (Matrigel). AB - Maintenance of long term culture and conventional xenografting of early B-lineage acute lymphoblastic leukemia cells is most difficult. Matrigel, a solubilized attachment matrix shown to aid growth of anchorage dependent solid tumors, was studied in heterotransplantation. Material for xenografting was derived from 5 patient bone marrow aspirates and 5 cell lines previously established and maintained by intraocular inoculation in nude mice. Specimens were injected by 3 methods: intraocular (n = 397); s.c. in medium (n = 78); and s.c. in medium supplemented by Matrigel (n = 69). With intraocular injection, 6 of 10 cell sources grew with respective ingraftment rates of 29-76%. Using the conventional s.c. method, no tumors resulted. The addition of Matrigel produced s.c. ingraftment from 8 of 10 cell sources (ingraftment rate, 50-100%). Immunophenotype, histopathology, and karyotype of the cells derived after Matrigel dependent ingraftment correlated with the cells of origin. It is concluded that Matrigel enables establishment and maintenance of early B-lineage acute lymphoblastic leukemia cell growth in a s.c. xenograft model. PMID- 8443801 TI - Preliminary mapping of the deleted region of chromosome 9 in bladder cancer. AB - Inactivation of a suppressor gene by deletion of chromosome 9 is a candidate initiating event in bladder carcinogenesis. We have used 13 polymorphic markers spanning the length of chromosome 9 in order to map the region of deletion in human bladder carcinomas. In the majority of tumors loss of heterozygosity was found at all informative sites along the chromosome, indicating deletion of the entire chromosome. Nine tumors had selective deletions of chromosome 9. Mapping of the deleted region in these tumors suggests that the target gene is located between D9S22 at 9q22 and D9S18 at 9p12-13. PMID- 8443802 TI - Regulation of fibroblast hepatocyte growth factor/scatter factor expression by human breast carcinoma cell lines and peptide growth factors. AB - Hepatocyte growth factor/scatter factor (HGF/SF) is a stromally derived modulator of epithelial cell proliferation and morphology. To better assess the potential role of HGF/SF in tumor progression we sought to identify factors and biological conditions which regulate its expression. We show that several adult human primary fibroblast cultures from breast and prostate produce HGF/SF. HGF expression in the MRC-5 human fetal lung fibroblast cell line is stimulated by conditioned media harvested from human breast tumor cell lines (MCF-7, T47D, and MDA-MB-231). In contrast, both indirect and direct coculture of each of these tumor lines with MRC-5 fibroblasts down-regulates HGF/SF expression. Finally, we show that MRC-5 HGF expression is inhibited by several known peptide growth factors, including transforming growth factor beta, epidermal growth factor, and transforming growth factor alpha. PMID- 8443803 TI - Cell killing and chromosomal aberrations induced in Chinese hamster ovary cells by treating with cisplatin at 41.5 degrees C during the G1 or late S phase. AB - Variation in sensitivity to cisplatin during the cell cycle was studied in synchronous Chinese hamster ovary cells treated during G1 or late S for 1 h at 41.5 degrees C with cisplatin (0.25-1.25 micrograms/ml, 0.8-4.2 x 10(-6) M). The cells were assayed for cell killing and chromosomal aberrations. Either they were plated for colony survival, or colcemid was added from 12 to 40 h after plating followed by fixation 4 h later for analysis of chromosomal aberrations after the cells completed 1 or 2 cycles (i.e., first or second mitosis). When the cells were treated either in G1 or late S, the cells entering metaphase exhibited primarily chromatid-type deletions and exchanges. However, aberrations were observed primarily in the first mitosis when cells were treated in G1 compared with aberrations being observed in both the first and second mitoses when cells were treated in late S. For a given amount of cytotoxicity or cytological damage, the cisplatin concentration at 41.5 degrees C could be reduced 4-6-fold compared with treatment at 37 degrees C. For low cisplatin concentrations of less than 0.5 0.7 microgram/ml (survival, approximately 0.3), heat killing predominated, and cells treated in S phase were more sensitive than those treated in G1. However, for cisplatin concentrations greater than 0.5-0.7 microgram/ml, cisplatin cytotoxicity predominated, and for both cell killing and chromosomal aberrations, the cells treated in G1 were approximately 1.5 times more sensitive than those treated in late S. Furthermore, the positive correlation between survival and aberration frequency was similar for cells treated at 37 degrees C or 41.5 degrees C in either G1 or late S. These results suggest that cisplatin administered at 37 degrees C or 41.5 degrees C causes cell lethality primarily by the induction of chromosomal aberrations. PMID- 8443804 TI - Characterization of the DNA double strand break repair defect in scid mice. AB - The scid mutation in CB-17 mice confers a profound immunodeficiency, resulting from an inability to rearrange immunoglobulin and T-cell receptor genes during lymphocyte development. Moreover, we and others have recently demonstrated in these scid mice a hypersensitivity to the lethal effects of ionizing radiation and a defect in DNA double strand break rejoining. In this report, we further characterize the radiosensitivity and repair defect in cells from scid mice. In order to determine whether scid cells were specifically sensitive to agents that produce double strand breaks, restriction enzymes RsaI and Sau3AI were introduced into scid and parental C.B-17 cells by electroporation. scid cells were 2-fold more sensitive than C.B-17 cells to both the blunt and the staggered end cuts produced by these restriction enzymes. However, the scid cells proficiently ligated both staggered and blunt ends of transfected plasmids. To determine whether the extent of DNA rejoining in scid cells was dependent on the initial dose of gamma-rays, final levels of DNA double strand break rejoining in scid and C.B-17 cells were quantitated by asymmetric field inversion gel electrophoresis. The results indicate an apparent difference in repair levels dependent on the dose of gamma-rays, ranging from 75% rejoining at 10 Gy to 40% rejoining at 50 Gy. In contrast, > 90% rejoining was observed in control C.B-17 cells at all doses. Delineating the links between these aberrant recombinational events, abnormal V(D)J recombination, and double strand break repair defects, will aid in the understanding of the basic mechanisms involved in these processes. PMID- 8443805 TI - Fluence rate effects in photodynamic therapy of multicell tumor spheroids. AB - EMT6/Ro spheroids approximately 500 microns in diameter were subjected to photodynamic therapy administered at various incident radiation fluence rates. Following 24 h incubation with 10 micrograms/ml Photofrin, groups of spheroids were irradiated at 630 nm with an identical fluence of 60 J/cm2, delivered at fluence rates ranging from 25 to 200 mW/cm2. After treatment, spheroids were dissociated, cell yields were determined, and surviving cells were assayed for their colony-forming ability. A surviving fraction was calculated for each treatment group by computing the product of the fractional cell yield and the plating efficiency. The results exhibit a strong dependence on the fluence rate, with surviving fractions decreasing from approximately 0.5 to 0.07 as the incident fluence rate was lowered from 200 to 25 mW/cm2. These data were analyzed using a mathematical model of photochemical oxygen consumption in spheroids undergoing photodynamic therapy. Calculations showed that therapy-induced oxygen consumption creates hypoxic volumes within which cells would be protected from singlet oxygen-mediated damage and that the magnitude of these hypoxic volumes depends on the radiation fluence rate. The fluence rate dependence of the spheroid cell survival was consistent with such an interpretation. PMID- 8443806 TI - The two major CD44 proteins expressed on a metastatic rat tumor cell line are derived from different splice variants: each one individually suffices to confer metastatic behavior. AB - The metastatic pancreas carcinoma cell line BSp73ASML produces a variety of different splice variants of the transmembrane glycoprotein CD44. The NH2 terminal portions are identical and heavily glycosylated. The variant sequences are inserted just outside the transmembrane region of the molecules. The two most abundant variants have 162 and 85 extra amino acids, respectively. When individually expressed, these suffice to establish metastatic properties in the nonmetastatic tumor cell line BSp73AS, as assayed by the spontaneous metastasis protocol. PMID- 8443807 TI - Sequence specificity in the interaction of the four stereoisomeric benzo[c]phenanthrene dihydrodiol epoxides with the supF gene. AB - The shuttle vector pS189 was treated with each of the four configurational isomers of benzo[c]phenanthrene 3,4-dihydrodiol 1,2-epoxide, and the modified DNA was used as a template in a polymerase arrest assay examining the supF gene. Sites at which polymerase (Sequenase, version 2.0) progress along the template was blocked were presumed to be at or near sites of adduct formation. The polymerase arrest sites were compared with recently reported mutation hotspots induced by these agents in this gene (Bigger et al., Proc. Natl. Acad. Sci. USA, 89: 368-372, 1992). For 31 of 32 mutation hotspots, a polymerase arrest band was present at or 1 or 2 nucleotides 3'- to that site, indicating that adduct formation tended to be associated with mutation hotspots. However, the arrest bands near mutation hotspots were not particularly prominent in all cases, and there were many sites of substantial polymerase arrest that were not in the vicinity of mutation hotspots. Thus, factors in addition to chemical selectivity must play key roles in determining sites of mutation. PMID- 8443808 TI - A direct comparison of immunological and clinical effects of interleukin 2 with and without interferon-alpha in humans. AB - Interleukin 2 (IL-2) and interferon-alpha (IFN-alpha) are cytokines with synergistic antitumor effects in mouse models. The biological effects of this combination, however, have not been directly compared to each agent alone in humans. We conducted a Phase 1B trial of IL-2 plus or minus IFN-alpha in 38 cancer patients. The objectives of this trial were to determine which doses of IFN-alpha and IL-2 maximally enhanced biological responses, and to determine whether the combined administration of IFN-alpha and IL-2 would result in a potentiation of biological responses over IL-2 alone. Patients received 4 days of IL-2 (1.5 x 10(6) units/m2/day or 3.0 x 10(6) units/m2/day) as a continuous infusion followed by a 3-day rest period, weekly for 3 weeks, with a 3-week rest period between 2 treatment courses. IFN-alpha (0.5 x 10(6) or 5 x 10(6) units/m2/day) was administered s.c. on days 1-4 weekly for 3 weeks with one of the 3-week courses. Patients were randomized to receive either IL-2 alone for course 1, followed by IL-2/IFN-alpha for course 2, or IL-2/IFN-alpha in course 1, followed by IL-2 alone. Immunological parameters were evaluated before treatment, and 24 h after completion of the third week of IL-2. A statistically significant increase in the percentage of circulating natural killer cells (CD56), natural killer cells bearing the Fc receptor (CD16), and activated T cells (CD25) was observed following IL-2 alone, and following IL-2 plus IFN-alpha. Significant increases in lymphocyte-activated killer cell cytotoxicity, antibody cellular cytotoxicity, and serum IL-2 receptor were also observed following both IL-2 and IL-2 plus IFN-alpha. However, no significant differences were observed in the magnitude of the increase in the IL-2-alone group when compared to the IL-2 plus IFN-alpha group. The mean fluorescent intensity of monocytes positive for HLA-DR and Fc receptor expression also increased significantly in both groups, as did serum beta 2-microglobulin expression and indoleamine 2,3-dioxygenase activity. However, increases were not significantly different between patients receiving IL 2 alone and IL-2 plus IFN-alpha. No dose response effect for IFN-alpha was observed for any of the parameters assessed. Toxicities consisted primarily of constitutional toxicities, including fever, rigors, malaise, headache, anorexia, and a decrease in performance status. No clinically significant differences in toxicities were observed between courses consisting of IL-2 and those consisting of IFN-alpha and IL-2.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8443809 TI - Androgen-induced inhibition of cell proliferation in an androgen-insensitive prostate cancer cell line (PC-3) transfected with a human androgen receptor complementary DNA. AB - A full length human androgen receptor complementary DNA was introduced into androgen receptor-negative PC-3 cells to determine if androgen sensitivity could be established in this cell line and to assess what influence, if any, androgen exposure would have on the growth of these cells. The androgen receptor complementary DNA was inserted into pSG5 in the region controlled by the SV40 promoter. This construct was cotransfected with pSR1neo into PC-3 cells and stably transfected cells were selected and screened for the expression of the androgen receptor. Active expression of the receptor was demonstrated by Western blotting using a rabbit anti-androgen receptor antiserum and by [3H]methyltrienolone binding to cytosol extracts. Saturation ligand-binding analysis revealed the presence of a single class, high affinity (Kd = 0.122 nM) androgen-binding site in cytosol extracts of transfected cells but not in extracts from mock-transfected cells. In cells expressing the transfected androgen receptor, androgen decreased the proliferation rate and cloning efficiency and induced a more differentiated phenotype. These results demonstrate that PC-3 cells have retained the mechanisms required to respond to the activated androgen receptor and that the loss of androgen sensitivity in these cells is due to the lack of functional androgen receptor. This also provides a technique for determining whether androgen-resistant tumor cells contain functional androgen receptors or whether androgen sensitivity is due to abnormalities in downstream signaling pathways. The apparent androgen-induced decreased malignant state of these transfected cells suggests new directions for the treatment of prostate cancer. PMID- 8443810 TI - Progesterone receptor expression in meningiomas. AB - The possibility that the female sex steroid progesterone plays a role in meningioma proliferation has been suggested by a number of investigators; and it had been shown that many meningiomas have high affinity progesterone binding sites. The aim of this study was to examine the expression of progesterone receptor mRNA and correlate it with the nuclear localization of progesterone receptor by immunocytochemistry in a large number of meningiomas. Thirty-three meningiomas were examined for the presence of measurable amounts of progesterone receptor mRNA by Northern blot analysis and 11 of these were analyzed for receptor protein by immunohistochemistry. These were compared with normal arachnoid and an arachnoid cell line. Sixty-four % of the meningiomas expressed progesterone receptor mRNA. This occurred in a similar pattern to what has previously been shown for T-47 D cells, a breast carcinoma cell line with 11.4-, 6.1-, 5.2-, 4.5-, 3.2-, and 2.5-kilobase mRNA species. This suggests that progesterone receptor expression is not tumor specific. There was a marked predominance of women among those patients whose tumors expressed progesterone receptor; 81% were female and 19% were male. The immunohistochemistry data correlate well with the Northern blot analysis. The staining was clearly nuclear, suggesting that the receptor is in a location to be activated. These data suggest that progesterone receptor mRNA and protein is expressed in meningiomas and support the concept that progesterone may play an important role in meningioma growth. PMID- 8443811 TI - Precancerous gastric lesions in a population at high risk of stomach cancer. AB - A population-based screening for detection of early cancers evaluated the prevalence of precancerous gastric lesions in an area in Shandong province, China, with one of the world's highest rates of stomach cancer. A total of 3433 residents aged 35 to 64 yr received gastroscopical examinations with biopsies taken from standard locations. Chronic atrophic gastritis was nearly universal; less than 2% of the population had biopsies showing entirely normal mucosa or only superficial gastritis. Intestinal metaplasia was the most advanced lesion for 33% and gastric dysplasia for 20%, although the prevalence of each increased significantly with age. Intestinal metaplasia and gastric dysplasia were detected throughout the stomach, but the lesions were more pronounced along the lesser curvature, especially in the angulus and antrum. There was no sex difference in rates of chronic atrophic gastritis, but males had a slightly higher prevalence of intestinal metaplasia, a 1.6-fold increase in dysplasia, and a 3-fold excess of gastric cancer. The data quantify the extensiveness of gastric lesions likely to be involved in the natural history of stomach cancer in this high-risk population. PMID- 8443812 TI - Aspirin use and risk of fatal cancer. AB - Aspirin and other nonsteroidal antiinflammatory drugs inhibit prostaglandin synthesis and tumor growth in many experimental systems, but it is unclear which of these tumor models are relevant to humans. We have reported reduced risk of fatal colon cancer among persons who used aspirin in a large prospective study. This analysis examines other fatal cancers in relation to aspirin among 635,031 adults in that study who provided information in 1982 on the frequency and duration of their aspirin use and did not report cancer. Death rates were measured through 1988. Death rates decreased with more frequent aspirin use for cancers of the esophagus, stomach, colon, and rectum but not generally for other cancers. For each digestive tract cancer, death rates were approximately 40% lower among persons who used aspirin 16 times/month or more for at least 1 year compared to those who used no aspirin. The trend of decreasing risk with more frequent aspirin use was strongest among persons who had used aspirin for 10 years or more; it remained statistically significant, except for esophageal cancer, in multivariate analyses that adjusted for other known risk factors. Biases such as early detection or aspirin avoidance among cases do not appear to explain the results. Our data suggest that regular, prolonged use of aspirin may reduce the risk of fatal cancer of the esophagus, stomach, colon, and rectum. Future epidemiological and basic research should examine all digestive tract cancers in considering the chemopreventive or therapeutic potential of nonsteroidal antiinflammatory drugs. PMID- 8443813 TI - Genistein arrests cell cycle progression at G2-M. AB - Genistein, an isoflavone, is a specific inhibitor of tyrosine kinase and topoisomerase II. However, its effect on cell growth is unknown. Therefore, we examined the effects of genistein on cell growth and cell cycle progression and compared its effects with other flavonoids. Genistein inhibited in a dose dependent manner the growth of HGC-27 cells derived from human gastric cancer. Flow-cytometric analysis showed that genistein almost completely arrested the cell cycle progression at G2-M. This effect was reversible when genistein was removed from the culture medium. In contrast, other flavonoids such as flavone, luteolin, and the structurally similar daidzein arrested the cell cycle at G1. Consistent with the flow-cytometric analysis, microscopic observation showed that genistein did not increase the mitotic index, which supposes that genistein may arrest the cell cycle at G2 or early M. These results suggest that the G2-M arrest by genistein is a unique effect among flavonoids. PMID- 8443814 TI - Increased NAD(P)H:(quinone-acceptor)oxidoreductase activity is associated with density-dependent growth inhibition of normal but not transformed cells. AB - The activity of DT-diaphorase [NAD(P)H:(quinone-acceptor)oxidoreductase] is increased 7-fold in wild-type BALB/c 3T3T cells as they reach confluence and become density growth arrested. Harvesting and replating the cells at low density resulted in a loss of DT-diaphorase with a half time of 7 h, and removal of serum from high-density growth-arrested cells resulted in a decrease in DT-diaphorase with a half time of 3 days. Platelet-derived growth factor and insulin together, but not singly, maintain elevated DT-diaphorase levels in high-density growth arrested BALB/c 3T3T cells. The increase in DT-diaphorase at high density diminished proportionately to the extent of transformation in four cell lines, 4NQO-3T3T, UV-3T3T, EJras-3T3T. and CSV3-1-3T3T. The most transformed cell line, CSV3-1-3T3T, showed no increase in DT-diaphorase at high density. Since there was no increase in DT-diaphorase mRNA in high-density growth-arrested wild-type BALB/c 3T3T cells compared to rapidly growing cells, the increase in DT diaphorase activity at high density is most likely due to posttranslational events. High-density growth-arrested wild-type BALB/c 3T3 cells exhibited a greater sensitivity to growth inhibition by the antitumor quinone diaziquone [1,4 cyclohexadiene-1,4- dicarbamic acid, 2,5-bis(1-aziridinyl)-3,6-dioxo-, diethyl ether], which is metabolically activated by DT-diaphorase, than do low-cell density, growth-arrested cells. The significance of the increase in DT-diaphorase at high cell density in normal cells and its loss in transformed cells may be related to the phenomenon of density-dependent growth inhibition in nontransformed but not in transformed cells. PMID- 8443815 TI - Efficacy of transferrin receptor-targeted immunotoxins in brain tumor cell lines and pediatric brain tumors. AB - The efficacy and cytotoxic properties of immunotoxin conjugates directed against the transferrin receptor were examined in cell lines and operative specimens from pediatric brain tumors. Dose-response relationships were assessed for immunotoxin mediated inhibition of protein synthesis for two immunotoxins, 454A12-rRA and anti-tfnR-CRM 107. Three target medulloblastoma cell lines (DAOY, D283MED, and D341MED), a glioblastoma (U373), and a neuroblastoma (SH-SY5Y) cell line exhibited similar sensitivity to both immunotoxins with IC50s in the 10(-9)-10( 10) M range. The time course of protein synthesis inhibition by the immunotoxins in DAOY cells showed that inhibition by anti-tfnR-CRM 107 was rapid and apparent by 6 h of incubation. In contrast, a response to 454A12-rRA was not observed until 16 h. Cell viability was decreased 30-40% by 24 h after removing 454A12-rRA (1 x 10(-9) M) and was maximally decreased 70-80% after 3 days. The efficacy of the immunotoxins on a variety of fresh specimens of pediatric brain tumors was also examined. The more aggressive and malignant tumor types such as glioblastoma multiforme and medulloblastoma had low IC50 values (10(-12) M), indicating that these tumors were extremely sensitive to transferrin receptor-targeted immunotoxins. In general, protein synthesis in slow-growing and benign tumors was not as greatly affected by immunotoxins. Immunoblots showed expression of transferrin receptors on the cell lines and tumors which correlated with in vitro sensitivity to immunotoxin. The results demonstrate that two immunotoxins targeted to the transferrin receptor are efficacious in killing brain tumor cell lines and primary tumor cultures at very low concentrations and that highly malignant tumors are especially sensitive to this cytotoxic response. PMID- 8443816 TI - Multidrug resistance is a component of V79 cell resistance to the alkylating agent adozelesin. AB - Adozelesin is a highly potent alkylating agent which has entered clinical trials based on its unique mechanisms of action and broad-spectrum antitumor activity in vivo. V79 cells resistant to adozelesin (V79/AdoR) were not resistant to the alkylating agent cisplatin but showed the phenotypic and genotypic characteristics of multidrug resistance. Thus V79/AdoR was cross-resistant to several structurally and functionally unrelated drugs, resistance was reversed by verapamil, and the resistant cell line expressed mdr mRNA and p170 glycoprotein. Also, adozelesin uptake and the amount of drug alkylated to DNA was much lower in the resistant cell line as compared to the sensitive parent. However, even with the same amount of drug bound to DNA (10 fmol/micrograms DNA) the survival of V79/S approximately 15% survival) was much lower than that of V79/AdoR (approximately 80%). Therefore the resistance of V79/AdoR cannot be explained solely by the multidrug resistance mechanism (i.e., lower drug uptake and less drug alkylation to DNA), which suggests that multiple mechanisms may account for resistance to adozelesin. V79/AdoR showed different levels of cross-resistance to several adozelesin analogues. The analogues could be divided into 2 groups; those with very low partition coefficients (log P < 2 as compared to 2.74 for adozelesin) had low levels of cross-resistance, whereas analogues with higher partition coefficients (log P > 2.4) were cross-resistant to adozelesin. PMID- 8443817 TI - T-cells infiltrating renal cell carcinoma display a poor proliferative response even though they can produce interleukin 2 and express interleukin 2 receptors. AB - The fact that progressing tumors contain a significant infiltrate of T-cells brings into question the competency of the infiltrating T-lymphocytes (T-TIL). We have examined the role of the T-cell receptor/CD3 complex and/or the interleukin 2 receptor (IL2R) in responsiveness of T-cells that infiltrate human renal cell carcinoma. T-TIL display a poor proliferative response to interleukin 2 (IL2) alone, IL2 in combination with antibody to CD3, or mitogen stimulation. The proliferative unresponsiveness was not related to low expression of CD3 or IL2R beta as the percentage of T-cells expressing CD3 and IL2R beta were comparable in both T-TIL and peripheral blood T-cells obtained from the same patient. In contrast to the lack of proliferative activity, stimulation of T-TIL or peripheral blood lymphocytes with phytohemagglutinin or anti-CD3 resulted in comparable levels of both IL2 and gamma-interferon mRNA and protein expression. While levels of IL2R alpha were low in unstimulated T-TIL and peripheral blood lymphocytes, anti-CD3 antibody or IL2 were capable of inducing surface expression of this protein in both cell populations. IL2R alpha mRNA levels were comparable in T-cells from the tumor and peripheral blood although in some experiments both the percentage of IL2R alpha-positive cells and the density of surface expression per cell were reduced in T-TIL. This reduced IL2R alpha expression on T-TIL was not responsible for the proliferative unresponsiveness since T-TIL that expressed both IL2R alpha and/or IL2R beta still failed to respond to high doses of IL2. Thus T-TIL display a selective loss of response to at least two well defined extracellular stimuli. While T-TIL exhibit a poor proliferative response regardless of the form of stimulation these cells remain sensitive to both anti CD3 and IL2 in terms of IL2 and gamma-interferon or IL2R alpha expression, respectively. The fact that proliferative unresponsiveness exists even though T TIL can produce IL2 and express IL2R alpha/beta suggests that T-TIL have a selective loss of a common intracellular signaling pathway which is requisite to proliferation but not other aspects of response to antigenic stimulation. PMID- 8443818 TI - Disseminated growth of a human multiple myeloma cell line in mice with severe combined immunodeficiency disease. AB - We have successfully engrafted a human multiple myeloma cell line, ARH-77, into C.B. 17 SCID mice. When ARH-77 cells were injected s.c., tumors grew only at the site of inoculation (five of five). When ARH-77 cells were injected i.v. tumors did not grow in any of the mice (zero of five). However, when mice were given gamma-irradiation with 150 rads and then inoculated i.v. with 10(7) ARH-77 cells, 100% (13 of 13) of the mice developed tumors. Hind leg paralysis was observed in 13 of 16 mice as a result of compression of the spinal cord by tumor. Histological analysis demonstrated that myeloma cells proliferated and formed osteolytic lesions (15 of 16) in the vertebrae and bones of the skull (14 of 16). Tumor cells also invaded the brain and meninges (14 of 16), lung (13 of 15), liver (seven of 15), and kidney (two of 15). Flow cytometric analysis demonstrated that the phenotype of 31% of the bone marrow cells in the vertebrae and 79% of s.c. tumor cells was similar to ARH-77 cells (CD38+, PCA-1+, HLA Classes 1 and II+). Furthermore, DNA hybridization with a human AluI probe confirmed their human origin. ARH-77-derived human immunoglobulin was detected in the serum of SCID/ARH-77 mice by ELISA. These observations demonstrate systemic involvement of human multiple myeloma following i.v. injection of ARH-77 cells into irradiated mice. This in vivo model should be useful for evaluating new therapeutic modalities for myeloma. PMID- 8443819 TI - Tissue inhibitor of metalloproteinase 1 is a negative regulator of the metastatic ability of a human gastric cancer cell line, KKLS, in the chick embryo. AB - Tissue inhibitors of metalloproteinases (TIMPs) are the negative regulators of matrix metalloproteinases that degrade extracellular matrix. We examined the regulatory role of TIMP-1 in the metastatic activity of human gastric cancer cell lines in chick embryos because unregulated matrix metalloproteinase activities are believed to be essential during metastatic processes. One of the nine cell lines examined, KKLS cells, formed metastatic colonies in the chick livers. These cells expressed undetectable levels of TIMP-1, and this was not inducible by 12-O tetradecanoylphorbol 13-acetate. Derivatives of KKLS cells with different levels of TIMP-1 expression were prepared by transfection of the human TIMP-1 complementary DNA controlled by a simian virus 40 early promoter. Metastatic abilities were suppressed by almost 70% in the transfectants expressing high levels of TIMP-1. In contrast, no suppression was observed in the control transfectants or in cells expressing the transfected TIMP-1 gene at low levels. These data indicate that a reduced expression of TIMP-1 in KKLS cells is responsible for their consequent metastatic potential. Moreover, it suggests that matrix metalloproteinase enzymatic activities are a prerequisite for metastatic activity in this experimental model system. PMID- 8443820 TI - Chemotaxis and chemokinesis of human prostate tumor cell lines in response to human prostate stromal cell secretory proteins containing a nerve growth factor like protein. AB - The migration of three human prostate tumor epithelial cell lines (TSU-pr1, PC-3, DU-145) in response to secreted protein from a human prostate stromal cell line was investigated by using the modified blind-well Boyden chamber assay. Migrated cells were quantified by spectrophotometrically measuring the concentration of crystal violet stain extracted from their nuclei. Cell number was correlated linearly with the concentration of extracted crystal violet stain. All three tumor cell lines showed intrinsic migratory ability in the absence of chemoattractants, such that approximately 1-7% of plated cells migrated across the filter of the Boyden chambers during a 5-h incubation period. Prostate tumor cell migration was significantly enhanced (3-13-fold) in response to stromal cell secretory protein in a dose-dependent manner, whereas bovine serum albumin had no effect on stimulating tumor cell migration. Immunoprecipitation of the stromal cell secreted protein with a nerve growth factor antibody partially and significantly reduced its stimulatory activity for tumor cell migration. A Zigmond-Hirsch matrix assay of tumor cell migration in response to various concentration gradients of stromal cell secreted protein demonstrated both chemotaxis and chemokinesis by all three cell lines. These results are consistent with the stromal cell secretory protein stimulation of chemokinetic tumor cell migration through the capsule of the prostate. Outside of the prostate gland metastasis of tumor cells may occur by chemotaxis to preferential sites containing chemoattractants similar to or related to maintenance factors that can substitute for components of stromal cell secretory protein. PMID- 8443821 TI - Radiation damage repair capacity of primary clonogenic blasts in acute lymphoblastic leukemia. AB - The sublethal radiation damage repair capacity of primary clonogenic blasts [i.e., leukemic progenitor cells (LPC)] from 74 newly diagnosed acute lymphoblastic leukemia (ALL) patients was analyzed using LPC colony assays. We determined the (a) Dq (quasithreshold dose) and n (extrapolation number) values from single dose radiation survival curves constructed according to the single hit multitarget model of cell survival, (b) beta values and alpha:beta ratios from single dose radiation survival curves constructed according to the linear quadratic model of cell survival, and (c) recovery factor values from survival data in split-dose experiments. Clonogenic blasts from different ALL patients varied substantially in their ability to repair sublethal radiation damage. However, in 11 of 30 (37%) T-lineage ALL cases and 13 of 44 (30%) B-lineage ALL cases, the radiation survival curves of fresh LPC were characterized by a distinct initial shoulder, providing circumstantial evidence that LPC from a significant portion of ALL patients (24 of 74 cases = 32%) are able to repair sublethal radiation damage. Leukemic progenitor cells from 23 of 34 (68%) evaluable cases evaluated had alpha:beta ratios of < 5 Gy, indicating that they may possess a substantial capacity to repair sublethal radiation damage. In order to further elucidate the repair capacity of ALL LPC, we compared the antileukemic efficacy of fractionated irradiation with 2 x 2 Gy to the antileukemic efficacy of single-dose irradiation with 1 x 4 Gy. In 20 of 28 cases (71%), a > or = 20% increase in LPC survival (recovery factor > or = 1.2) was observed when 4 Gy were delivered in two doses instead of a single dose, providing direct evidence that ALL LPC are able to repair sublethal radiation damage. Our results indicate that modifications in total body irradiation regimens, currently administered prior to bone marrow transplantation, may be necessary to diminish the probability of relapse in high-risk ALL. PMID- 8443822 TI - Mucin synthesis and secretion in various human epithelial cancer cell lines that express the MUC-1 mucin gene. AB - Previous studies have suggested that mucin gene expression is tissue-specific; however, the relationship between unique mucin gene products and the biochemical properties of mucins is unknown. The purpose of this study was to determine the biochemical and molecular characteristics of mucin synthesized by adenocarcinoma cell lines derived from breast (ZR-75-1), stomach (MGC-803), pancreas (Capan-2), and lung (Chago K-1). Mucin was quantitated by [3H]glucosamine labeling and Sepharose CL-4B chromatography. The mucinous nature of the labeled high molecular weight glycoproteins (HMG) was verified by alkaline borohydride treatment, cesium chloride density gradient ultracentrifugation, and sodium dodecyl sulfate polyacrylamide gel electrophoresis. Specific mucin gene expression was determined using cDNA probes for 2 distinct intestinal mucins (MUC-2 and MUC-3) and one breast cancer mucin (MUC-1). Specific core mucin proteins were confirmed by immunoblots using antibodies that recognize MUC-1, MUC-2, and MUC-3 core peptides. These experiments demonstrate that all cell lines contained HMG in the medium, cytosol, and membrane fractions. The HMG was mucinous in breast, pancreatic, and lung cell lines. In contrast, most of the HMG secreted by the gastric cell line was proteoglycan-like, due to its susceptibility to hyaluronidase, heparinase, and chondroitinase avidin-biotin complex. Ion-exchange (DEAE-Sephacel) chromatography of [3H]glucosamine-labeled HMG demonstrated that the acidic or basic nature of the mucin was different in all cancer cell lines tested. Despite these differences, mRNA and immunoblot analysis suggest that all cell lines predominantly express MUC-1 apomucin, small amounts of MUC-2 apomucin, and no MUC-3. Immunoprecipitation of MUC-1-type mucin using the 139H2 monoclonal antibody demonstrated that different sizes of mucin peptides were present in all cell lines, corresponding to the known length polymorphism of this mucin. The amount and nature of carbohydrate epitopes were analyzed by immunoblots using anti-T (peanut lectin), anti-Tn (91S8 monoclonal antibody), and anti-sialosyl Tn (JT10e monoclonal antibody). T and Tn antigens were significantly higher in breast and pancreatic cells as compared with lung and gastric cell lines. These findings correlated with increased activities of polypeptidyl N acetylgalactosaminyl transferase and beta-1,3-galactosyltransferase.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8443823 TI - Expression of BCL-2 protein enhances the survival of mouse fibrosarcoid cells in tumor necrosis factor-mediated cytotoxicity. AB - Tumor necrosis factor (TNF) kills some types of tumor cells in vitro and participates in tumor elimination in vivo. TNF has been shown to kill cells by altering their mitochondria structurally and functionally. The oncogene BCL-2 codes for a protein located in the inner membrane of mitochondria which is able to inhibit the commitment to cell death in various cell types. We have therefore investigated whether TNF-mediated killing of the cell line L929 could be modulated by expression of the protein BCL-2. We report here that L929 cells transfected with a BCL-2 expression vector have an increased survival compared to wild type cells after TNF challenge. The protective effect is greatest at moderate TNF concentrations and is still significant at concentrations that killed 100% of wild type cells. The action of BCL-2 is selective inasmuch as cells are not protected against other cytotoxic agents blocking various mitochondrial functions. We show that cells expressing BCL-2 have a higher mitochondrial membrane potential (delta psi) than wild type cells. The increase in delta psi could be linked with the enhanced survival of cells after TNF challenge. Indeed, we found that treatment of wild type L929 cells with the ionophore nigericin, which increases delta psi, protects them even at high TNF concentrations. PMID- 8443824 TI - Human cytotoxic T-cell lines with restricted specificity for squamous cell carcinoma of the head and neck. AB - Human cytotoxic T-lymphocyte (CTL) lines with specificity restricted for autologous squamous cell carcinoma of the head and neck (SCCHN) were established from peripheral blood lymphocytes obtained at the time of surgery and again at two different times after surgery from a patient with cancer of the tongue. The CTL lines were cultured in the presence of interleukin (IL) 2, IL4, and autologous tumor (AuTu) cell monolayers. All three lines were CD3+CD8+CD11b-HLA DR+ T-cell receptor alpha/beta+. They were tested in 4-h51Cr release assays against SCCHN cell lines (n = 5) and a variety of nonsquamous human tumor (n = 5) and normal (n = 5) cell targets and was found to lyse only AuTu (PCI-50) and three allogenic SCCHN cell lines. Lysis of AuTu and the three allogenic SCCHN targets by the established CTL lines appeared to be major histocompatibility complex class I restricted, since it was blocked by monoclonal antibodies to class I histocompatibility complex antigens. The CTL lines proliferated in vitro in response to autologous PCI-50 or an allogenic SCCHN cell line (PCI-1). The lines have been maintained in culture in the presence of AuTu monolayers and retained cytotoxicity against AuTu for over 20 weeks. The AuTu (PCI-50) cell line was tested for in vitro sensitivity to cytotoxic or cytostatic effects of various effector cells, including the CTL lines. PCI-50 targets were resistant to lysis by resting human mononuclear cells but sensitive to IL2-activated natural killer cells in 4-h 51Cr release assays. In comparison with IL2-activated natural killer cells, the CTL line mediated lower levels of lysis against AuTu. Growth of PCI-50 cells in culture was significantly inhibited by a combination of gamma-interferon and IL2 or by high concentrations of tumor necrosis factor alpha. While supernants of IL2-activated natural killer cells were growth inhibitory, those of the CTL line were not. On the other hand, lysis of AuTu targets by the CTL line was increased by preincubation of the tumor cells with tumor necrosis factor alpha or gamma-interferon. These cytokines augmented expression of HLA-class I, HLA-class II, and intercellular adhesion molecule I, but not squamous cell carcinoma-associated antigens, E7 and A9, on PCI-50 cells. The CTL lines described are the first with restricted specificity for autologous SCCHN ever reported and their availability will facilitate studies of the AuTu T-cell response in head and neck cancer. PMID- 8443825 TI - Correspondence re: S. E. Benner et al., Chemoprevention strategies for lung and upper aerodigestive tract cancer. Cancer Res., 52 (Suppl.): 2758s-2763s, 1992. PMID- 8443826 TI - Avian epidermis contains ATPase- and Ia-positive Langerhans-like cells. AB - The occurrence of cells resembling mammalian Langerhans cells in the avian epidermis was studied by ATPase histochemistry, Ia immunoreactivity and electron microscopy. The existence of MHC class II antigen-(Ia) expressing, ATPase positive dendritic cells, which are ultrastructurally similar to mammalian Langerhans cells except for the absence of Birbeck granules, was demonstrated. These cells may be a basic component of the immune system of birds. PMID- 8443827 TI - Development of the diffuse endocrine system in the chicken proventriculus. AB - The development of endocrine cells in the chicken proventriculus has been investigated using light- and electron-microscopy in conjunction with silver and immunocytochemical techniques. The first morphologically detectable endocrine cells were found in 5-day-old embryos by electron microscopy. From the 9th to the 13th day, endocrine cells in contact with the lumen of the organ could be detected both by electron and light (silver impregnation) microscopy. The number of open-type endocrine cells progressively decreased and the number of closed type increased after this stage. Until the 16th day, endocrine cells were located exclusively in the luminal epithelium, but afterwards they appeared in progressively greater numbers in the compound glands. After hatching, long cytoplasmic processes could be seen in the endocrine cells. Immunoreactivities to regulatory substances appeared in the following order: serotonin (day-14), avian pancreatic polypeptide, glucagon and somatostatin (day-16), bombesin and neurotensin (day-18), and finally, met-enkephalin (day-21). PMID- 8443828 TI - Distribution of NADPH-diaphorase activity in rat paravertebral, prevertebral and pelvic sympathetic ganglia. AB - Paravertebral (superior cervical and stellate), prevertebral (coeliac-superior mesenteric, inferior mesenteric) and pelvic (hypogastric) sympathetic ganglia of the rat were investigated by enzyme histochemistry to ascertain the distribution of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-diaphorase) activity. In the paravertebral ganglia the majority of the sympathetic neuronal perikarya contained lightly and homogeneously distributed formazan reaction product but there was a range of staining intensities amongst the neuron population. In contrast, in the prevertebral ganglia, intense NADPH-diaphorase staining was present in certain neurons. Firstly, a population of neurons of the coeliac-superior mesenteric ganglion complex were surrounded by densely NADPH diaphorase-positive 'baskets' of fibres and other stained fibres were seen in interstitial nerve bundles and in nerve trunks connected to the ganglion complex. Secondly, in both the inferior mesenteric ganglion and hypogastric ganglion there were many very intensely NADPH-diaphorase positive neurons. Stained dendritic and axonal processes emerged from these cell bodies. In both ganglia this population of neurons was smaller in size than the lightly stained ganglionic neurons and commonly had only one long (presumably axonal) process. The similarity of these highly NADPH-diaphorase-positive neurons with previously described postganglionic parasympathetic neurons in the hypogastric ganglion is discussed. PMID- 8443829 TI - Junctions between pericytes and the endothelium in rat myocardial capillaries: a morphometric and immunogold study. AB - Pericytes are cells of mesodermal origin which are closely associated with the microvasculature. Despite numerous studies little is known about their function. We have studied the relationship between pericytes and the endothelium in rat myocardial capillaries employing ultrastructural and immunogold techniques. 14% of the subendothelial cell membrane is covered by comparatively small pericytic cell processes. About half of these processes are completely embedded in basement membrane material, whereas the remaining half forms closer contacts with the endothelium. These contacts are devoid of anti-laminin immunogold label, a marker for basement membranes. A small fraction of these contacts has been identified as tight junctions resembling those seen between endothelial cells in capillaries of the same tissue. The remaining majority of junctions reveals a cleft of approximately 18 nm between the apposed membranes in which a succession of cleft spanning structures can often be detected. It was also found that pericytic processes are preferentially located close to interendothelial junctions. We suggest that the high frequency of intimate junctions between pericytes and the endothelium and the preferential localisation near paracellular clefts may have functional significance. PMID- 8443830 TI - Immune-complex-trapping cells in the spleen of the oriental fire-bellied toad, Bombina orientalis. AB - The spleen of the oriental fire-bellied toad, Bombina orientalis, consists of well-developed white pulp, separated from the lymphocytic marginal zone by the connective tissue boundary layer. Injection of peroxidase-conjugated rabbit anti peroxidase revealed that these immune complexes were localized on the surface of acid-phosphatase-positive and non-specific-esterase-positive cells in the white pulp. The majority of immune-complex-trapping cells were present around the blood vessels. Cell processes of some of these cells penetrated into the wall of blood vessels. The significance of the present findings is discussed with respect to the evolution of immune-complex-trapping cells in the spleen. PMID- 8443831 TI - Plasma membrane alterations of maturing goat (Capra indicus) spermatozoa: lectin binding and freeze-fracture study. AB - A qualitative and quantitative analysis of lectin-binding sites has been undertaken on spermatozoa recovered from different regions of the epididymis of the goat (Capra indicus) using fluorescein isothiocyanate-linked lectins (Bauhinia purpurea BPA, Concanavalin A Con A, Dolichos biflorus DBA, Maclura pomifera MPA, Arachis hypogaea or peanut agglutinin PNA, Glycine max or soyabean agglutinin SBA, Ulex europaeus UEA, and Triticum vulgaris or wheat-germ agglutinin WGA), in conjunction with scanning and transmission electron microscopy, and freeze-fracture techniques. Flow cytometric analysis has also been used to quantitize binding affinity. Spermatozoa from caput to cauda epididymidis show no significant variation in lectin-binding ability, but the samples removed from the corpus epididymidis contain a greater number of binding sites. The passage of spermatozoa through the epididymidis is accompanied by a redistribution of the plasma membrane lectin-receptors covering the sperm head and tail. Receptors for BPA, DBA, PNA and SBA are specifically restricted to the anterior region of the acrosome in caudal spermatozoa. Freeze-fracture replicas, examined to study changes in organisation of intramembranous particles of the plasma membrane during sperm maturation, reveal distinct changes in their distribution in the acrosome, post-acrosome and spermatozoon tail, especially in the corpus and cauda epididymidis. PMID- 8443832 TI - Cysteine-proteinase localization in osteoclasts: an immunocytochemical study. AB - Cysteine-proteinases such as cathepsin B and G were localized in rat osteoclasts, by an indirect protein A-immunogold labeling technique, on post-embedded ultrathin sections. In osteoclasts, specific immunogold labeling of both anti cathepsin B and G was localized in Golgi vesicles, lysosomes, pale vacuoles of various sizes, and the extracellular canals of ruffled borders; no immunoreactivity was seen in the cytoplasmic matrix, mitochondria, cisterns of the rough endoplasmic reticulum, or nuclei. The presence of immunolabeling of cathepsins in osteoclasts and in the subosteoclastic compartment suggests that these enzymes are involved in the extracellular degradation of collagen and other non-collagenous bone matrix proteins. PMID- 8443833 TI - Immunohistochemical localization of transforming growth factor-alpha and epidermal growth factor-receptor in the mesonephros and metanephros of the chicken. AB - Transforming growth factor-alpha (TGF-alpha) is a polypeptide related to epidermal growth factor (EGF). Both bind to EGF-receptor (EGF-R) to carry out their function in a variety of tissues and cell lines. Several studies have shown their presence in mammalian kidney, however, nothing has to date been stated concerning their existence in avian kidney. Expression of TGF-alpha and EGF-R is reported here for the first time during the development of the chicken kidney. Using immunohistochemical techniques, we identified a TGF-alpha (but not EGF) in mesonephric distal tubule cells from day 8 to day 20 of embryonic development and in metanephric distal tubule cells from day 14 of embryonic development to the adult. The histochemical characteristics of these cells and their histological localization suggest that they may be the "principal cells" of the distal tubules. Similarly, EGF-R was found in mesonephric proximal tubule cells from day 7 to day 18 of embryonic development and in metanephric proximal tubule cells from day 13 of embryonic development up to adult stages. The coexistence of both TGF-alpha and EGF-R from the onset of development of mesonephros and metanephros supports their possible role in mechanisms of proliferation and differentiation of the cells of these organs. PMID- 8443834 TI - Ultrastructural distribution of DNA within the nucleolus of various animal cell lines or tissues revealed by terminal deoxynucleotidyl transferase. AB - We have used the highly sensitive in situ terminal deoxynucleotidyl transferase method, applied to ultrathin sections, to investigate the location of DNA within nucleoli of various animal cells. In all the nucleoli studied, intense labelling is revealed over the peri- and intranucleolar condensed chromatin. Gold particles are also consistently found over the fibrillar centres, especially at their periphery, namely in the border area between the fibrillar centres and the dense fibrillar component, whereas the dense fibrillar component itself seems to be free of label in nucleoli in which these two compartments can be distinguished. We conclude that, in transcriptionally active nucleoli of this type, DNA is a characteristic constituent of the fibrillar centres, distinguishing them functionally from the dense fibrillar component. Some nucleoli exhibit neither fibrillar centres nor a dense fibrillar component, but have a single, albeit heterogeneous accumulation of fibrillar material; gold particles are consistently seen over some parts of this fibrillar compartment. This suggests that certain parts of the fibrillar material are functionally similar to the fibrillar centres of those nucleoli that possess them. PMID- 8443835 TI - Isolated brush cells of the rat stomach retain their structural polarity. AB - The brush cells (BC) are highly polarized elements occurring in epithelia of endodermal origin. They have a preferential topographical distribution in the organs in which they reside. In the stomach of the rat, BC prevail near the transitional zone separating the forestomach from the glandular stomach. Thus, a method was developed to isolate and recover BC from this organ with the aim of investigating the changes they may undergo after dissociation. Strips of the rat stomach were severed from the very proximal border of the glandular region and incubated in Hanks' balanced salt solution containing pronase. After sedimentation of the dissociated cells (crude sediment containing all stomach epithelial cell types) two successive cell fractions were prepared on performed Percoll gradient in an attempt to enrich BC in a defined layer. BC were recovered in a fraction at a density close to 1.03 g/ml where they represented about 2% of all cells. The isolated BC changed their form from columnar to pear-shaped; however, they maintained their structural polarity over 2 h as demonstrated by light microscopy, transmission-and scanning-electron microscopy. The fine structure of BC was always satisfactorily preserved. Maintenance of the structural polarity of isolated BC is contrary to the general rule according to which all conventional epithelial cells examined to date lose their polarity after isolation. This result is discussed in relation to morphological findings in isolated sensory cells (hair cells, photoreceptor cells) leading to the suggestion that BC are more similar to these than to conventional epithelial cells. PMID- 8443836 TI - Immunofluorescent studies on Z-line-associated protein in cultured cardiomyocytes from neonatal hamsters. AB - The organization of the cytoskeletal proteins, alpha-actinin, vinculin and desmin, was studied in newborn hamster cardiomyocytes in vitro by immunofluorescent microscopy. Since there have been indications that the in vitro organization of certain cytoskeletal elements of cardiomyocytes is not the same as in vivo, the studies were designed to examine the reorganization of these proteins in cultured cells. The observations concentrated on three proteins that are known to be associated in vivo with myofibrillar Z-lines. Beginning at 2 days in culture, and during subsequent days, the proteins examined underwent substantial redistributions before they reorganized back to their associations with the myofibrillar Z-lines. The pattern and time course for these redistributions were characteristic for each protein. Alpha-actinin was the first to return to its typical location at the level of the Z-lines during the second day in culture, followed by desmin at 4 days. Vinculin usually did not become associated with the Z-lines until 6 days in vitro. In the present study, analyses of the distributions and redistributions of particular proteins in the cultured cardiomyocytes have been useful for helping to identify changes in the myocyte as a result of isolation and culture conditions. In addition, a better understanding of the temporal and spatial relationships between cytoskeletal proteins assembling into the Z-line area has been gained. PMID- 8443837 TI - Glycoconjugates with Neu5Ac(alpha 2,6)Gal(beta 1,4)GlcNAc sequences: a selective lectin-histochemical property of Kurloff cells in guinea pig thymus. AB - The Kurloff cell (KC), a natural killer lymphocyte, contains a large (10-microns diameter) periodic acid-Schiff (PAS)-positive lysosome-like inclusion body called the Kurloff body (KB), which exhibits strong acid phosphatase activity. The presence of Sambucus nigra agglutinin (SNA)-reactive Neu5Ac(alpha 2,6)-D-Gal/Gal NAc(beta 1,4)GlcNAc oligosaccharide sequences and the absence of the corresponding Neu5Ac(alpha 2,3) Maackia amurensis agglutinin (MAA)-reactive sequence in the major 35-kDa N-glycosylproteins of the complex or hybrid type extracted from purified KC were established by Western-lectin-blotting of cytosolic extracts from purified KC. Moreover, these SNA-reactive sequences, or at least part of them, were shown to be borne by sialidase-sensitive KC acid isophosphatases. Thymic sections rich in KC, from estrogenized guinea pigs were examined by affino-histochemistry with these sialic acid-reactive lectins. The SNA-reactivity of thymic sections was quasi-exclusively confined to KC clusters, whereas the whole thymic section was negative for MAA. KC were not SNA-reactive following preincubation and incubation with 200 mM lactose. When submitted to enzymatic or mild chemical desialylation processes, the SNA-reactivity of the KC clusters was enhanced. The SNA-reactivity of KC clusters was completely abolished following prolonged chemical desialylation, whereas the PAS-positivity of KB remained unchanged. Even after a prolonged sialidase treatment, this SNA reactivity was only reduced. Moreover, after both these desialylation processes, KC developed a heavier Ricinus communis agglutinin-reactivity, thus confirming the presence of penultimate Gal residues in their abundant SNA-reactive oligosaccharide sequences Neu5Ac(alpha 2,6)Gal(beta 1,4)GlcNAc. Such a selective lectin histochemical property provides a marker for detecting KC. PMID- 8443838 TI - Immunohistochemistry and nerve lesion experiments on the methionine-enkephalin immunopositive neurons in the small intestine of the bullfrog (Rana catesbeiana). AB - Nerve elements in the small intestine of the bullfrog. Rana catesbeiana, were studied by immunohistochemistry with anti-methionine enkephalin antisera and by nerve lesion experiments, using laser irradiation. Methionine-enkephalin immunopositive nerve fibers occur in the myenteric plexus, circular muscle layer, submucosa, and mucosa. Immunopositive nerve cell bodies in the myenteric plexus have dendrite-like and a long axon-like processes. In the froglet (3 months after metamorphosis), these axon-like processes lead posteriorly in the nerve strand of the myenteric plexus. Some bifurcate, one branch continuing posteriorly, the other doubling back to lead anteriorly; both form terminal varicose fibers in the circular muscle layer. Nerve lesion experiments, in the adult bullfrog, resulted in accumulations of methionine-enkephalin immunoreactivity at the oral and hinder edges of the laser-irradiated necrotic area; there were sprouting and nonsprouting immunopositive stumps. It is suggested that bidirectional flow of methionine-enkephalin in the myenteric plexus is mediated via the anterior and posterior branches of the axon-like process. The difference in sprouting behavior of immunopositive nerve fiber stumps, after nerve lesion, is discussed with reference to regional differences of the axon-like process. PMID- 8443839 TI - The circadian system of crustaceans. AB - Crustaceans exhibit a variety of overt circadian rhythms. Observations on intact animals suggest the existence of more than one circadian pacemaker in the nervous system. Ablation experiments so far have been inconclusive in pin-pointing the location of putative pacemakers. However, various structures, most notably the optic peduncle, have been shown to sustain circadian rhythmicity in vitro. Retinal sensitivity and neurosecretory activity display circadian rhythms in the isolated optic peduncle, but they are also responsive to synchronizing influences from other regions of the central nervous system, most notably the supraesophageal ganglion. A model based on a number of circadian pacemakers distributed in the central nervous system best fits the experimental results at present. Coupling of rhythmicity between independent circadian pacemakers is likely to occur, and a neuroendocrine stage of integration has been proposed for several rhythms. Various entraining agents have been identified, and more than one may play a part in the synchronization of a given rhythm. PMID- 8443840 TI - Chronobiologic aspects of a coadaptive process: the interaction of Ludwigia elegans flowers and their more frequent bee visitors. AB - Field observations spanning 1 year of the visits of two bee species- Tetraglossula bigamica (Hymenoptera: Colletidae) and Pseudagapostemon brasiliensis (Hymenoptera: Halictidae)--to the flowers of Ludwigia elegans (Onagraceae) evinced the existence of circadian and circannual components in the rhythms of activity both of plant and bees. In addition to morphological adaptations to the flower, the bees were temporally adjusted to each other and to the flower's opening and closing mechanisms. At the observation locality (Ribeirao Preto, Sao Paulo, Brazil--latitude 21 degrees-21 degrees 30S), the plant bloomed year-round. The flowers of the same population open simultaneously at the onset of the photophase, pollen and nectar being available almost immediately. Withering occurs in the afternoon of the same day. Although many bee species visited the flowers, T. bigamica and P. brasiliensis were the most frequent visitors, but their yearly rhythms were phased opposite to one another. Circadian rhythms were detected in pollen and nectar harvest. Comparisons of acrophases showed significant differences for males' and females' nectar collecting rhythm and for females' pollen harvest rhythm. As for the circannual component, acrophases of all rhythms occur at progressively later times from December to July when the migration is reversed until November. These data strongly suggest that the relationship between L. elegans and T. bigamica and P. brasiliensis is in accordance with a clearly temporal pattern and that the two bee species are temporally separated in nature. PMID- 8443841 TI - Gastric potential difference in fasted rats: circadian studies. AB - The pathophysiology of gastroduodenal ulcer disease remains the subject of intense research and controversy. One model of gastric ulcerogenesis implicates a disruption of complementary circadian rhythms between protective and destructive factors. Parallel circadian rhythms have been reported between acid secretion and gastric potential difference (PD) in in vitro models. The purpose of this study was to investigate the circadian measurements of PD, a parameter of intact gastric mucosal function and thus a putative parameter of gastric protection, in intact, fasted, anesthetized rats. Sixty-four male Sprague-Dawley rats were acclimatized in sound-attenuating, lightproof chambers for 3 weeks on a 12:12-h light-dark schedule. Eight rats were fasted 18 h before being sampled at each of eight times on the circadian clock (01:00, 04:00, 07:00, 10:00, 13:00, 16:00, 19:00, and 22:00 hours after lights on) (HALO). In each rat, after anesthesia (ketamine/acepromazine) and laparotomy, the tip of a catheter (pre-filled with KCl agar) was passed into the gastric corpus through the duodenum. The tip of a second KCl-agar catheter was placed within the peritoneal cavity. The position of the intragastric catheter was gently adjusted for obtaining the highest stable PD reading. The data showed significantly higher values at 07:00 and 10:00 HALO. The lowest value was at 13:00 HALO. The difference between high (10:00 HALO) and low (13:00 HALO) values was 4.5 mV or 13% of the mean. This difference was highly significant (p = 0.003) Analysis of variance showed that the values at 07:00 and 10:00 HALO were significantly higher than the values at 01:00, 13:00, and 16:00 HALO.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8443842 TI - Circannual variations in blood cholesterol levels. AB - The seasonality of blood cholesterol is still not well established. Some have described a seasonal pattern with highest levels during autumn and lowest in summer, whereas others have reported no change. A number of studies showed circannual variations with maximum levels in winter and minimum in summer. The aim of this study was to examine the circannual variation of cholesterol in a large cohort in Israel. In the Israeli CORDIS study, employees of 21 factories were screened for cardiovascular disease risk factors during 1985-7. As part of the information gathered, serum cholesterol and blood counts were available for 3,726 men and 1,514 women. Serum cholesterol levels fit a circannual rhythm assessed by the cosinor analysis. Highest levels of serum cholesterol were found in spring and lowest in summer. We conclude that there is a circannual change of serum cholesterol, which could be partially associated with changes in environmental temperature. The circannual variation in serum cholesterol was considerable and should be taken into account when carrying out clinical evaluation of patients. PMID- 8443843 TI - New data on the ontogeny of the child's sleep-wake rhythm. AB - The present study is part of a broader body of research concerning the ontogeny and regulations of the young child's sleep-wake rhythm. It was carried out with 12 children admitted to a day-care center from 4 or 5 months of age. None of the children showed any anomalies or functional disorders. The method used in this study consisted in organizing a data collection on the alternations of wakefulness and sleep as well as on the children's behavior throughout the 24-h period, both in their family and at the day-care center from 4 to 15 months of age. The main findings are (a) the circadian rhythm of wakefulness and sleep is clearly set up as early as at 4 months of age and consolidates between 6 and 7 months; (b) some ages are characterized by significant changes in the daily distribution and duration of sleep spans: 6 to 7 months; 10 to 12 months; 13 to 15 months; (c) these changes suggest the existence of several ultradian rhythmicities which become successively prevailing from one age to the next throughout child development. The longitudinal study of the young child's sleep wakefulness rhythm allows better evaluation of the influence of developmental factors in its structuralization and formulation of new hypotheses on its disorders and dysfunction. Individual factors are under study. PMID- 8443844 TI - Circannual variation in the incidence of uterine cervix cancer. AB - The impact of uterine cervix cancer (UCC) can be greatly reduced by regular vaginal examination and other preventive measures. With this aim, UCC screening programs had been developed and applied for several years in Mexico and elsewhere. One point still to be considered in such preventive programs is the possible circannual pattern in the morbidity or mortality of UCC. With the aim of identifying a possible circannual pattern of variation in the incidence of UCC, we analyzed the monthly totals of positive detected cases of UCC in the state of Nuevo Leon (Mexico) between 1978 and 1987. For eliminating bias due to the seasonal variation in the number of preventive check-ups, data were first expressed in percentage of tests done in the same month. The least-squares fit of a 1-year cosine curve to the data reveals a statistically significant circannual pattern (p = 0.013), with a maximum of relative incidence detected in February. Results indicate UCC incidence higher than the yearly average during the winter, with secondary peaks in August and November. This pattern of variation is similar if one considers separately for analysis the relative incidence of type III, IV, or V UCC (relating to cases suggesting, highly suggesting, or concluding a malignant alteration, respectively). For evaluating the cost-effectiveness of the UCC screening campaign providing these data, the monthly totals of screening check-ups done over the same period were also analyzed. Results reveal a statistically significant circannual rhythm (p < 0.001), with a maximum detected in June.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8443845 TI - Sleep and heart rate circadian rhythm in depression: the necessity to separate. AB - In order to determine whether a decrease in the amplitude of heart rate circadian rhythm (HRCR) could represent a chronobiological marker of depression and to answer the question of the possible role of this alteration in the reduction of rapid eye movement sleep latency (REM latency) observed in depression, 22 major depressed patients (DSM III R, Montgomery Asberg Depression Rating Scale) and 11 healthy volunteers entered this study, which included the simultaneous recordings of sleep and heart rate (HR) during two consecutive 24-h periods. After a smoothing procedure, the HR data, obtained from a portable device providing mean HR/min, were computed with the single cosinor method for the classical circadian parameters. We also determined the cosinor fitting index (CFI = percentage to fit). When studied as a single group and compared to the control group, the depressed patients, who had difficulties in sleep initiation and whose REM latencies were within normal limits, were characterized by a dampening of the amplitude HRCR and of the day-night HR difference. This was linked to a lesser increase of HR during the day and a reduced decrease at night. No significant phase modification of HRCR was observed in this group of depressives. In a second step, the depressives were divided into a depressed arrhythmic group (DAG, CFI < 50%, 11 patients) and a depressed rhythmic group (DRG, CFI > 50%, 11 patients) who did not differ on MADRS scores. Even though the amplitude of HRCR was reduced in the DAG only, with HR higher at night and lower during the daytime than for controls, both DAG and DRG significantly differed from controls on those items related to sleep induction and maintenance. In the DAG only was there a tendency toward a reduction of total sleep time and REM sleep time while REM latency was normal. This finding suggests that sleep problems are not responsible for the differences in HRCR parameters between the two depressed groups. These differences in HR and sleep parameters between two groups of similarly depressed patients also suggest that a short REM latency does not systematically imply a disruption of all circadian clocks. PMID- 8443846 TI - Circadian rhythm of cardiac output, peripheral vascular resistance, and related variables by a beat-to-beat monitoring. AB - This study aimed to explore the 24-h patterns of stroke volume, cardiac output, and peripheral vascular resistance along with other correlated variables, such as left ventricular ejection time, ejection velocity index, thoracic fluid index, heart rate, and blood pressure. The study was performed on 12 clinically healthy subjects by means of a noninvasive beat-to-beat monitoring using the thoracic electric bioimpedance technique associated with the automated sphygmomanometric recording. Time data series were analyzed by means of chronobiological procedures. The results documented the occurrence of a circadian rhythm for all the variables investigated, giving relevance to the beat-to-beat bioperiodicity of cardiac output and peripheral vascular resistance. Temporal quantification of the investigated variables may be useful for a better insight of the chronophysiology of the cardiovascular apparatus. PMID- 8443847 TI - A simple classification of the risk in cardiac surgery: the first decade. AB - Since 1980, the operative risk in all our cardiac surgical patients has been assessed before surgery. In light of reports of changes in cardiac surgical populations, we reexamined our practice and risk classification. The purpose of this study was to compare the surgery performed, the characteristics of the patients operated upon and the hospital mortality in our institution in two epochs ten years apart. In 1989-90, the 2029 consecutive cardiac surgical patients who had the same operations as the 500 patients of a 1980 study in our institution were prospectively stratified using our risk classification based on the number of risk factors (RFs) present: normal-risk patient = no RF, increased risk = 1 RF, high risk > or = 2 RFs. These two cohorts of patients were compared. From 1980 to 1990, the proportion of high-risk patients tripled whereas the proportion of normal-risk patients diminished by one third and the proportion of increased risk remained unchanged. The incidence of the following RFs increased: poor left ventricular function, advanced age, emergency surgery, reoperation and other systemic disorders. In coronary artery surgery patients, the incidence of unstable angina/recent myocardial infarction and of obesity also increased. In noncoronary artery surgery patients, the incidence of heart failure increased while obesity remained unchanged. The difference in hospital mortality among the three risk classes was significant within both study periods. The mortality in each risk class and total mortality did not change between 1980 and 1990.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8443848 TI - Minute ventilation during mask halothane anaesthesia in infants and children. AB - The pattern of respiration in infants during anaesthesia is not well documented. In this study, minute ventilation (MV) during elective mask halothane anaesthesia (HA) was measured during spontaneous ventilation in infants (Group I) and children (Group II). Airflow was measured with pneumotachography (#0 Fleisch in Group I and #1 Fleisch in Group II). Analogue signals of pressure and flow were recorded on magnetic tape for off-line playback. The flow signal was mathematically integrated to volume. The surgical procedure was divided into three stages: A, B and C representing HA, surgical stimulation and emergence respectively. The pattern of respiration during spontaneous ventilation was described as tidal volume (VTx), respiratory frequency (fx), mean inspiratory flow (VT/TIx), inspiratory duty cycle (TI/TTotx) where the subscript x denoted the stage. Seven infants (2.7 +/- 0.5 mo, 5.8 +/- 0.5 kg) and five children (3.1 +/- 1.1 yr, 15.8 +/- 1.7 kg) were studied. There was no difference in MV between Groups I and II. Halothane anaesthesia in both groups was characterized by rapid shallow breathing: VTA was lower in Group I (2.90 +/- 0.8 ml.kg-1) than in Group II (3.74 +/- 0.40 ml.kg-1) (P < 0.05). Tidal volume was lower during anaesthesia than emergence in both groups (P < 0.05). There was no difference in VT/TIx between groups. The VT/TIA was lower than VT/TIC in Group I (P < 0.05) but not in Group II. There was no intra or intergroup difference in TI/TTot between stages. We suggest that during HA infants have a greater reduction in VT than children, which may predispose infants to hypercarbia during HA. PMID- 8443849 TI - Nasal ketamine for paediatric premedication. AB - Ketamine in a dose of 6 mg.kg-1 was nasally administered in 86 healthy children (ASA I and II), aged from two to five years undergoing elective general, urological or plastic surgery, 20 to 40 min before the scheduled surgery time. These children were compared with 62 others, also aged from two to five years, in whom promethazine and meperidine, 1 mg.kg-1 of each, were injected im. Sedation was started as excellent in 48 and as adequate in 19 children in the ketamine group, compared with nine and 12 respectively in Group 2 (P < 0.05), while salivation was similar in both groups. We conclude that nasal ketamine is an alternative to im preanaesthetic sedation administration in children aged from two to five years. PMID- 8443850 TI - Airway irritation produced by volatile anaesthetics during brief inhalation: comparison of halothane, enflurane, isoflurane and sevoflurane. AB - Eleven male volunteers were studied to compare the airway irritation produced by the four anaesthetic agents: halothane, enflurane, isoflurane and sevoflurane at two concentrations, equivalent to one and two MAC. Tidal volume, respiratory frequency and functional residual capacity changes induced by 15 sec inhalation of the anaesthetics were measured using respiratory inductive plethysmograph. Appearance of the cough reflex was also observed. The order of subjective airway irritation was evaluated by the volunteers. Inhalation of the anaesthetic agents induced a decrease in tidal volume, increase in respiratory frequency and decrease in functional residual capacity. Significant changes were considered to have occurred if tidal volume and respiratory frequency changed by more than 30% from the resting values for at least ten seconds, or if functional residual capacity changed by more than 30% of the value at resting tidal volume, for at least ten seconds. Each change was induced most frequently by isoflurane followed by enflurane, halothane and, least frequently, by sevoflurane. The orders of appearance of the cough reflex and of subjective airway irritation were similar. Sevoflurane did not elicit a cough reflex. It is concluded that sevoflurane was the least irritant anaesthetic and is considered to be the most suitable for inhalational induction of anaesthesia. PMID- 8443851 TI - Pharmacodynamic behaviour of rocuronium in the elderly. AB - This study compared the potency and time course of action of rocuronium (ORG 9426) in elderly and young patients during nitrous oxide-opioid anaesthesia. One hundred ASA physical status I-II patients (60, aged 65-80 yr, and 40, aged 20-45 yr) were studied by measuring the force of contraction of the adductor pollicis in response to train-of-four stimulation of the ulnar nerve. After induction of anaesthesia with thiopentone and maintenance with N2O/O2 and fentanyl, rocuronium 120, 160, 200, or 240 micrograms.kg-1 was administered to determine dose-response curves. When maximum block had been obtained, further rocuronium to a total of 300 micrograms.kg-1 was given. Additional doses of 100 micrograms.kg-1 were administered when the first twitch height (T1) had recovered to 25% control. At the end of surgery neuromuscular blockade was allowed, whenever possible, to recover spontaneously until T1 was 90% of control before administration of neostigmine. There was no difference in the potency of rocuronium in the elderly and the younger patients. The ED50 was 196 +/- 8 (SEE for the mean) in elderly, vs 215 +/- 17 micrograms.kg-1 in young patients (NS). When individual cumulative dose-response curves were constructed, the ED50 was 203 +/- 7 (SEM) and 201 +/- 10 micrograms.kg-1 in the elderly and the young respectively (NS). However, the onset of maximum neuromuscular block was slower in the elderly 3.7 +/- 1.1 (SD) vs 3.1 +/- 0.9 min, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8443852 TI - Audit of intensive care unit admissions from the operating room. AB - An audit of 265 intensive care unit (ICU) admissions from the operating room was performed for the year 1991. In a quality assurance exercise we identified 34 unanticipated ICU admissions (UIAs) by a retrospective peer review of the medical charts. Of these UIAs, 16 were deemed predictable and seven preventable. Five of the seven potentially preventable UIAs were judged to have had inappropriate intravenous fluid management. This has prompted changes in our education programme. In an assessment of our resource management, we evaluated prospectively collected data on the Apache II scores on the day of admission, the incidence of ICU-specific interventions, length of stay in ICU, and outcomes. ICU specific interventions were not initially required in 36% of admissions and these patients had a low risk (1.1%) of eventually requiring ICU-specific interventions. In comparison with patients requiring ICU-specific interventions, they had lower Apache II scores (10.2 vs 13.1), shorter ICU stays (medians of one vs two days), lower ICU mortality (0 vs 8.2%), P < 0.05, but hospital mortality was not different (7.4 vs 15.3%). This audit has prompted reorganisation of our intensive care services, so that patients not requiring ICU-specific interventions will be managed in an intermediate care area with nurse:patient ratios of 1:3 or 4, in comparison with 1:1 or 2 ratios in the intensive care area. PMID- 8443854 TI - Rheumatoid cervical joint disease--a challenge to the anaesthetist. AB - Cervical joint disease in rheumatoid arthritis patients is common. These patients may be at risk for severe life-threatening neurological problems in the perioperative period and thus present a challenge to the anaesthetist. By understanding the various anatomical abnormalities that may occur in rheumatoid cervical joint disease, the anaesthetist can design an appropriate management plan for the patient. The destruction of normal anatomy by rheumatoid arthritis can result in atlanto-axial subluxation (AAS) or subaxial subluxation. The atlanto-axial subluxation is further divided anatomically into anterior AAS, posterior AAS, vertical AAS, and lateral/rotatory AAS. In addition to the history and physical examination of the rheumatoid arthritis patient, radiological evaluation of the cervical spine is highly recommended. With the identification of the specific anatomical lesion the anaesthetist can predict and avoid movements which may lead to, or worsen, neurological problems. In the event of an emergency where full evaluation of the cervical spine is not possible the anaesthetist must presume that the rheumatoid patient has severe cervical spine instability and use the most cautious approach. PMID- 8443855 TI - Hypertension and pulmonary oedema associated with ketamine administration in a patient with a history of substance abuse. AB - Cocaine use, frequently associated with other substance abuse, is becoming more common in the pregnant patient. These patients are more likely to experience peripartum complications. A case of hypertension and pulmonary oedema in such a patient, possibly triggered by ketamine, is reported. A tumultuous course in the intensive care unit was resolved when the patient's hypertension and sympathetic reactivity were successfully treated with barbiturates. A number of factors supported a diagnosis of barbiturate withdrawal in this patient, its onset also was related temporally to ketamine administration. Hypertension should be considered a sign of acute barbiturate withdrawal. If a history of cocaine use, particularly crack cocaine, is elicited, one should suspect multiple substance abuse and be especially cautious when administering ketamine. PMID- 8443853 TI - Errors in the measurement of cardiac output by thermodilution. AB - Cardiac output (CO) determination by thermodilution, which was introduced by Fegler in 1954, has gained wide acceptance in clinical medicine and animal experiments because it has several advantages over other methods with respect to simplicity, accuracy, reproducibility, repeated measurements at short intervals, and because there is no need for blood withdrawal. However, errors in determination of CO by thermodilution may be introduced by technical factors and the patients' pathological conditions. The current review summarizes these issues and provides our recommendations, based on the medical literature published between 1954-1992. To obtain more reproducible and accurate CO values by thermodilution, one should make several determinations (1) by using 10 ml injectate at room temperature for adults and 0.15 ml.kg-1 injectate for infants and children; (2) at evenly spaced intervals of the ventilation cycle; (3) when rapid intravenous fluid administration is discontinued; (4) by observing thermodilution curves so that baseline pulmonary artery temperature drift or the existence of intra- and extracardiac shunts are noticed. Finally, CO determination by thermodilution may be unreliable or impossible in patients with low CO states and tricuspid or pulmonary regurgitation. Since non-invasive CO monitoring has not replaced CO determination by thermodilution, intimate knowledge of this method is crucial for anaesthetists to prevent errors in the management of patients. PMID- 8443856 TI - In vitro determination of human dura mater permeability to opioids and local anaesthetics. AB - The permeability of human thoracic and lumbar dura mater to various compounds in clinical use was determined in vitro. Sections of dura mater, 3 to 4 cm in diameter, obtained at post-mortem were placed between the ports (area = 3 cm2) of two glass chambers (A and B) which fitted tightly together to form a two-chamber apparatus for measuring permeability through the dura. Each chamber contained 5 ml of artificial cerebrospinal fluid. A sample of test drug solution was introduced into one chamber (A) and 50 microliters aliquots were withdrawn from the other chamber (B) at predetermined intervals. Permeability was determined by calculating the rate of diffusion (slope) from the plot of mean drug concentration (chamber B) versus time. Dura mater permeability was shown to be a simple diffusion process and to be independent of lipid-solubility and molecular weight. Permeability appeared to increase with age and may have a linear relationship to the initial concentration. PMID- 8443857 TI - Modification by CO2 of endothelin-1-induced contraction of isolated guinea pig trachea. AB - To investigate the effect of changes in CO2 tension on airway smooth muscle tone induced by various agonists, contractile responses to acetylcholine, histamine and endothelin-1 (ET-1) were studied in isolated guinea pig tracheae at very low PCO2 (16 +/- 0 mmHg, n = 38), moderately low PCO2 (28 +/- 0 mmHg, n = 23), normal PCO2 (38 +/- 1 mmHg, n = 70) or high PCO2 (94 +/- 1 mmHg, n = 32). The minimum concentration of ET-1 (10(-10) M) needed to induce contractions was lower than that of acetylcholine (10(-7) M) and histamine (10(-7) M) at normal PCO2. Changes in PCO2 did not significantly affect acetylcholine- or histamine-induced contractions. In contrast, very low and moderately low PCO2 attenuated the contractions induced by ET-1, but high PCO2 potentiated those induced by a high concentration of ET-1. Very low PCO2 with normal pH and with high pH attenuated the contractions caused by ET-1, whereas normal PCO2 with high pH did not. These results suggest that ET-1-induced airway smooth muscle contraction can be modified by PCO2 per se. Aspirin and indomethacin potentiated the responses to ET 1 at very low PCO2 more than at normal PCO2, but attenuated the responses to low concentration of ET-1 at high PCO2. These results also suggest that cyclooxygenase-related eicosanoids are involved in the effects of PCO2 on ET-1 induced contractions. PMID- 8443858 TI - Does hypothermia or hyperventilation affect enflurane MAC reduction following partial cardiopulmonary bypass in dogs? AB - This study in dogs determined the effect of systemic cooling and arterial hypocarbia during cardiopulmonary bypass (CPB) on the requirements for enflurane anaesthesia (MAC) before and after CPB. Twelve mongrel dogs were each anaesthetized with enflurane in oxygen on two separate occasions. End-tidal enflurane concentration was measured with a Puritan-Bennett Anaesthesia Agent Monitor. Using the tail-clamp method, MAC was determined twice with a one-hour interval between measurements (MAC 1 and MAC 2). Partial CPB was then initiated using femoral arterio-venous cannulation and maintained for one hour. Following separation from CPB, MAC was again determined twice with a one hour interval between measurements (MAC 3 and MAC 4). Dogs were randomly assigned according to PaCO2 management during CPB (low, 17.6 +/- 8.6 mmHg vs high, 38.9 +/- 11.5 mmHg), and then subjected to two experimental conditions. The first experiment on each dog was undertaken using normothermia during CPB (warm, 35-37 degrees C) while the second experiment (at least two weeks later) was conducted using hypothermia during CPB (cold, 30 degrees C). Analysis of the data, using ANOVA for repeated measures, revealed MAC 3 (1.95 +/- 0.33%, post-CPB) to be reduced when compared with MAC 1 (2.18 +/- 0.28%, P < 0.01) or MAC 2 (2.10 +/- 0.22%, P < 0.01), determined before CPB. Multivariate repeated measures analysis revealed no independent effects of hypothermia or arterial hypocarbia during CPB, on MAC reduction. By the time of the second experiment in each dog (two weeks later), MAC had returned to baseline levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8443859 TI - Flow velocity profile of the pulmonary artery measured by the continuous cardiac output monitoring catheter. AB - The KATS catheter (continuous arterial thermodeprivation system catheter) measures the blood flow velocity of the pulmonary artery (PA) by thermodeprivation which enables continuous determination of cardiac output. The accuracy of this system may depend on the degree of uniformity of flow velocity in the PA, because small movements of the catheter within the PA are inevitable with a beating heart. We evaluated the flow velocity profile of the PA in seven anaesthetized open-chest dogs to assess these potential errors. A custom-made stiff catheter, at the tip of which was incorporated the flow velocity sensor of the KATS catheter, was used to penetrate the main PA in the short axis direction (perpendicular to flow direction) or the long axis direction (along flow direction). The stiff catheter was moved in increments of 2.5 mm, and flow velocity was recorded. The wall-to-wall distance of the PA along each direction was divided into five sections (S1 to S5 for the short axis, and L1 to L5 for the long axis). Flow velocity data for each section were averaged and presented as relative values against the control mid-point velocity. Along the short axis, flow velocity was 0.41 +/- 0.20 (SD), 1.00 +/- 0.10, 1.03 +/- 0.10, 1.08 +/- 0.13 and 0.49 +/- 0.26 from S1 to S5, i.e., lower in S1 and S5 which were close to the vascular walls (P < 0.05) but uniform in other areas. Along the long axis, flow velocity was 0.28 +/- 0.28, 0.88 +/- 0.09, 0.94 +/- 0.08, 1.06 +/- 0.25 and 1.28 +/- 0.50 from L1 to L5.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8443860 TI - Georges Cousineau (1906-1987). PMID- 8443861 TI - Combined lumbosacral plexus block. PMID- 8443862 TI - Finger pulse oximeter response. PMID- 8443863 TI - Risk-adjusted mortality to assess quality of care in cardiac surgery. PMID- 8443864 TI - Continuous cardiac output: myth or reality? PMID- 8443865 TI - Altered vascular responses to platelets from hypercholesterolemic humans. AB - Activated platelets release potent vasoactive factors. Previous studies have focused on mechanisms by which vascular abnormalities lead to altered responses of atherosclerotic arteries. We tested the hypothesis that the activation of platelets from hypercholesterolemic humans produces abnormal vascular responses. Responses to intraluminal and abluminal activation of platelets from normal subjects and type II hypercholesterolemic patients (total cholesterol, 274 +/- 16 [mean +/- SEM] mg/dl) were examined in carotid arteries from normal rabbits perfused in vitro. Intraluminal activation of normal platelets produced pronounced dilatation of arteries preconstricted with phenylephrine. Vasodilator responses to intraluminal activation of platelets from hypercholesterolemic patients were greatly impaired. Vasodilator responses to platelets from hypercholesterolemic patients were not restored to normal by LY53,857 (10(-5) M), a 5-hydroxytryptamine2-serotonergic antagonist, by SQ29,548 (10(-5) M), a thromboxane A2/prostaglandin H2 receptor antagonist, or by apyrase (1.5 units/ml), an enzyme with ADPase activity. Abluminal activation of normal platelets produced modest constriction in quiescent arteries, and abluminal activation of platelets from hypercholesterolemic patients produced augmented vasoconstrictor responses. The major finding is that vasodilator responses to platelets from hypercholesterolemic patients are profoundly impaired, and vasoconstrictor responses to platelets from hypercholesterolemic patients are augmented. Mechanisms in addition to increased release of serotonin, thromboxane, and ADP appear to contribute to impaired vasodilator responses to hypercholesterolemic platelets. Thus, alteration of platelets by hypercholesterolemia, as well as altered vascular reactivity, may contribute to abnormal vascular responses in atherosclerosis. PMID- 8443866 TI - Computer simulations of three-dimensional propagation in ventricular myocardium. Effects of intramural fiber rotation and inhomogeneous conductivity on epicardial activation. AB - Three-dimensional membrane-based simulations of action potential propagation in ventricular myocardium were performed. Specifically, the effects of the intramural rotation of the fiber axes and inhomogeneous conductivity on the timing and pattern of epicardial activation were examined. Models were built, with approximately 400,000 microscopic elements arranged in rectangular parallelepipeds in each model. Simulations used the nonlinear Ebihara and Johnson membrane equations for the fast sodium current. Constructed models had histological features of ventricular myocardium. All models were anisotropic. In a subset of the models, an abrupt intramural rotation of the fiber axes was included. This feature was also combined with randomly distributed inhomogeneous conductivity and regions of high transverse resistance to represent nonuniform anisotropy in a further subset of the models. Epicardial stimuli were applied for each simulation. Three-dimensional activation patterns and epicardial isochron maps were constructed from the simulations. We noted that the rotation of fiber axes accelerated epicardial activation distant from the stimulus site. The inhomogeneous conductivity caused regional acceleration and deceleration of activation spread. We also noted features of epicardial activation that resulted from the fiber rotation, and the inhomogeneous conductivity corresponded to that observed in maps from experimental animals. PMID- 8443867 TI - Characterization of protein kinase C isotype expression in adult rat heart. Protein kinase C-epsilon is a major isotype present, and it is activated by phorbol esters, epinephrine, and endothelin. AB - The pattern of protein kinase C (PKC) isotype expression in whole extracts of dispersed, freshly isolated adult rat ventricular myocytes and adult rat heart ventricle was examined by immunoblot analysis using antisera specific for PKC alpha, -beta 1, -gamma, -delta, -epsilon, -zeta, or -eta isotypes. This analysis revealed significant levels of expression of the Ca(2+)-independent isotype PKC epsilon, which was detected as band of 97-kd molecular mass. PKC-zeta was detected principally as a 66-kd band that probably represented a proteolytic product of the holoenzyme. PKC-eta was detected only in whole ventricle as a doublet at 75 and 81 kd and was therefore probably present in nonmyocytic cells. PKC-alpha, -beta 1, -gamma, and -delta could not be detected. Because of our inability to detect PKC-alpha, -beta 1, -gamma, and -delta in whole extracts, PKC isotypes were partially purified from whole heart by DEAE Sepharose chromatography. PKC-alpha, -beta 1, -gamma, and -delta could still not be detected in the appropriate fractions. All PKC isotypes were detectable in appropriate positive control extracts (brain or certain cultured cell lines). In unstimulated isolated cardiomyocytes, the majority (80-95%) of the PKC-epsilon immunoreactivity was present in the soluble fraction of the extract. On exposure of the cardiomyocytes to 1 microM phorbol 12-myristate 13-acetate (PMA), PKC epsilon undergoes a rapid (< 30 seconds), sustained (at least 60 minutes), and virtually complete association with the Triton X-100-soluble membrane fraction. There was an associated loss of PKC-epsilon from the soluble fraction. The EC50 for PMA of the translocation event was 15-37 nM. Exposure of cardiomyocytes to 1 microM 4 beta-phorbol 12,13-didecanoate or 1 microM phorbol 12,13-dibutyrate also resulted in translocation of PKC-epsilon to the membrane fraction, whereas exposure to 1 microM 4 alpha-phorbol 12,13-didecanoate was without effect. PKC epsilon also translocated on exposure of cardiomyocytes to 50 microM epinephrine or 100 nM endothelin-1. However, in both cases, the extent of translocation was significantly less than that after exposure to PMA. We conclude that interventions that lead to hypertrophy of cardiomyocytes (phorbol esters, epinephrine, and endothelin-1) activate PKC-epsilon. PMID- 8443868 TI - Effect of dysfunctional vascular endothelium on myocardial performance in isolated papillary muscles. AB - Vascular endothelium has been shown to modify the contractile characteristics of vascular smooth muscle, and endocardial endothelium has been shown to modify the contractile characteristics of adjacent myocardium. In this study, whether vascular endothelium also modifies the contractile characteristics of adjacent myocardium and whether these effects are additive to those of endocardial endothelium were investigated. Rabbit hearts (n = 54) were excised and mounted in a Langendorff preparation. Vascular reactivity was verified by acetylcholine infusion. One group of these hearts had Triton X-100 injected as a bolus into the coronaries to render the vascular endothelium dysfunctional. The other portion served as control hearts. Triton X-100 bolus injection resulted in little or no pathological changes on morphological examination; however, the vasodilatory response to acetylcholine in these hearts was abolished, suggesting vascular endothelial dysfunction. Vascular smooth muscle reactivity was verified in Triton X-100-injected hearts by nitroprusside infusion. In the control Langendorff perfused hearts, there was little evidence of vascular endothelial dysfunction, with the coronary perfusion rate increasing from 8.9 +/- 0.4 to 11.0 +/- 0.3 ml/g per minute (p < 0.01) in response to acetylcholine. All hearts were then removed, and right ventricular papillary muscles were excised for myocardial mechanical studies. Control Langendorff-perfused hearts had myocardial mechanical characteristics similar to those of muscles from 18 other control hearts without Langendorff perfusion, indicating that the Langendorff perfusion itself had little effect on myocardial mechanics. The muscles from the Triton X-100-injected Langendorff hearts had marked changes: a shortening of twitch duration (363 +/- 16 versus 449 +/- 9 msec, p < 0.01) and decreases in total tension (2.2 +/- 0.2 versus 2.9 +/- 0.2 g/mm2, p < 0.01), dT/dt (9 +/- 1 versus 12 +/- 1 g/mm2 per second, p < 0.05), and maximum velocity of unloaded muscle shortening (Vmax) (0.89 +/- 0.06 versus 1.14 +/- 0.07 length at which maximum developed tension occurred [Lmax]/sec, p < 0.05). Endocardial endothelial removal of the papillary muscles in the two control groups (with and without Langendorff perfusion) by Triton X-100 caused the same changes in twitch characteristics as occurred in muscles from the Langendorff-perfused hearts injected with Triton X-100 but with intact endocardial endothelium, suggesting that vascular endothelial dysfunction had similar effects on contractile characteristics as endocardial endothelial removal.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8443869 TI - Intense sympathetic stimulation releases neuropeptide Y but fails to evoke sustained coronary vasoconstriction in dogs. AB - We determined whether a 3-minute period of intense cardiac sympathetic stimulation, which is known to release neuropeptide Y (NPY), elicits a sustained poststimulatory coronary vasoconstriction in anesthetized dogs that had received propranolol. We also periodically measured the cardiac chronotropic responses to test vagal stimulations; these responses served as an index of the neuronal release of NPY. In a group of 11 animals, the coronary vascular resistance increased by 14 +/- 4% during the sympathetic stimulation. After cessation of stimulation, however, coronary vascular resistance returned rapidly to its control value. The cardiac responses to the test vagal stimuli were attenuated by approximately 40% after cessation of sympathetic stimulation, and this inhibitory effect persisted for approximately 60 minutes. In a second group of eight dogs, we determined whether the intense sympathetic stimulation potentiates the coronary vascular responses to exogenous norepinephrine (NE). Before sympathetic stimulation, standard intracoronary infusions of NE increased coronary vascular resistance by 14 +/- 2%. Intense antecedent sympathetic stimulation did not alter the coronary vascular responses to subsequent NE infusions. However, the chronotropic responses to test vagal stimuli were initially attenuated by approximately 30%, and this inhibitory effect persisted for approximately 1 hour. In a third group of four dogs, we found that exogenous NPY significantly potentiated the coronary vasoconstriction evoked by NE infusions. The coronary vascular responses to combined infusions of NE and NPY were consistently greater (by approximately 13%) than the sum of the responses to these substances when they were infused separately. We conclude that, even though sufficient NPY appears to be released from the sympathetic nerve endings to inhibit vagal neurotransmission, the quantity of NPY released into the coronary blood vessels under the conditions of our experiments appears to be insufficient either to elicit a sustained coronary vasoconstriction or to potentiate the vasoconstrictor effects of intracoronary NE infusions. PMID- 8443871 TI - Physiological pH. Effects on posthypoxic proximal tubular injury. AB - After O2 deprivation, tissue acidosis rapidly self-corrects. This study assessed the effect of this pH correction on the induction, and pathways, of posthypoxic proximal tubular injury. In addition, ways to prevent the resultant injury were explored. Isolated rat proximal tubular segments (PTSs) were subjected to hypoxia/reoxygenation (50/30 or 30/50 minutes) under the following incubation conditions: 1) continuous pH 7.4, 2) continuous pH 6.8, or 3) hypoxia at pH 6.8 and reoxygenation at pH 7.4 (NaHCO3 or Tris base addition). Continuously oxygenated PTSs maintained under these same pH conditions served as controls. Lethal cell injury was assessed by lactate dehydrogenase (LDH) release. pH effects on several purported pathways of hypoxia/reoxygenation injury were also assessed (ATP depletion, lipid peroxidation, and membrane deacylation). Acidosis blocked hypoxic LDH release (pH 7.4, 50 +/- 2%; pH 6.8, 6 +/- 1%) without mitigating membrane deacylation or ATP depletion. During reoxygenation, minimal LDH was released (3-5%) if pH was held constant. However, if posthypoxic pH was corrected, immediate (< or = 5 minutes) and marked cell death (e.g., 55 +/- 3% with Tris) occurred. This was dissociated from lipid peroxidation or new deacylation, and it was preceded by a depressed ATP/ADP ratio (suggesting an acidosis-associated defect in hypoxic/posthypoxic cell energetics). Realkalinization injury was not inevitable, since it could be substantially blocked by 1) posthypoxic glycine addition, 2) transient posthypoxic hypothermia, or 3) allowing a 10-minute reoxygenation (cell recovery) period before base addition. Neither mannitol nor graded buffer Ca2+ deletion conferred protection. Acute pH correction caused no injury to continuously oxygenated PTSs. Conclusions are as follows: 1) Posthypoxic "pH shock" causes virtually immediate cell death, not by causing de novo injury but, rather, by removing the cytoprotective effect of acidosis. 2) This injury can be prevented by a variety of methods, indicating a great potential for salvaging severely damaged posthypoxic PTSs. PMID- 8443870 TI - Flow-related responses of intracellular inositol phosphate levels in cultured aortic endothelial cells. AB - In vitro and in vivo evidence indicates that hemodynamic wall shear stress evokes a diversity of biological responses in vascular endothelial cells, ranging from cell shape changes to alterations in low density lipoprotein receptor expression. The signal transduction mechanisms by which the level of fluid mechanical shear stress is recognized by the endothelial cell and translated into these diverse biological responses remain to be elucidated. The present study focuses on the association between the onset of elevated shear stress and activation of the phosphoinositide signal transduction pathway, as measured by the intracellular release of inositol phosphates, in cultured bovine aortic endothelial cells (BAECs). BAECs were seeded, grown to confluence on large polyester sheets, and preincubated with 0.3 microCi/ml [3H]inositol for 24 hours before insertion in parallel-plate flow chambers for exposure to high shear stress (HS) at 30 dynes/cm2 or low shear stress (LS) at < 0.5 dyne/cm2 for periods ranging from 15 seconds to 24 hours. The induction of HS was associated with an early, transient but significant increase (142%, HS/LS x 100%) in inositol trisphosphate (IP3) measured at 15 seconds of shear stress exposure followed by a major peak in IP3 (189%) observed at 5 minutes after HS onset. After these initial increases, IP3 levels returned to near resting levels within 30 minutes of continued HS exposure and then continued to decline to significantly lower (75%) levels relative to LS treated cells within 4 hours and remained lower throughout the remainder of the 24-hour HS exposure. LS-treated cells exhibited no significant changes in inositol phosphate levels throughout the 24-hour exposure periods. Exposure of BAECs to shear stress of 60 dynes/cm2 resulted in an approximately fourfold increase in IP3 levels (396%) measured at 5 minutes, almost double the levels measured in cells exposed to 30 dynes/cm2 for 5 minutes. Pretreatment of BAECs for 30 minutes with 5 mM neomycin, an inhibitor of phosphoinositide metabolism, before HS exposure inhibited both the early increases in inositol phosphates and subsequent cell elongation and alignment observed in untreated BAECs simultaneously exposed to HS without inhibiting protein synthesis. These results indicate that the exposure of cultured BAECs to elevated wall shear stress is associated with an early biphasic IP3 increase followed by a resetting of intracellular inositol phosphate concentrations to levels below that observed in static cultured BAECs. Furthermore, neomycin inhibition of this IP3 response to shear stress is associated with an inhibition of one of the major endothelial biological responses to shear stress, i.e., cell shape change and orientation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8443872 TI - Regulation of Ca2+ transport by platelet-derived growth factor-BB in rat vascular smooth muscle cells. AB - The present study investigates the effects of platelet-derived growth factor (PDGF) isoform BB (PDGF-BB) on cytosolic Ca2+ concentration ([Ca2+]i), Ca2+ transport, and Ca2+ pools in rat vascular smooth muscle (VSM) cells. VSM cells from thoracic aorta of Milan normotensive rats were enzymatically dispersed, cultured in 10% serum medium, and made quiescent by 72 hours in 0.3% serum medium. [Ca2+]i, Ca2+ influx, Ca2+ efflux, and exchangeable cell Ca2+ pool were evaluated by ratiometric fluorescent and radioisotope techniques. Ca2+ transport showed time-dependent changes during stimulation with PDGF-BB. The initial early responses to this peptide were transient rise in [Ca2+]i, a 30% decrease in Ca2+ influx, and a 3.6-fold increase in the rate constant for active Ca2+ efflux. Stimulation of Ca2+ efflux and inhibition of Ca2+ influx were associated with a substantial 30% reduction in the cell Ca2+ pool. This initial stimulation of Ca2+ efflux is concomitant with Ca2+ mobilization into the cytosol and is due to activation of Na(+)-independent Ca2+ efflux via the Ca2+ pump. After a 10-minute stimulation, Ca2+ influx returned to the basal value, whereas Ca2+ efflux remained 2.2-fold above control values, leading to a decline in [Ca2+]i below basal levels and a further decrease in the cell Ca2+ pool. Nearly half of this late Ca2+ efflux appears to be driven by Na(+)-Ca2+ exchange, as evidenced by its external Na+ dependence. After a 120-minute stimulation with PDGF-BB, nifedipine sensitive Ca2+ influx is increased 37% above basal levels, and Ca2+ efflux remains elevated. During prolonged stimulation by PDGF-BB, both Ca2+ influx and efflux are stimulated, resulting in a new intracellular Ca2+ homeostasis marked by the recovery of the cell Ca2+ pool but a lowered [Ca2+]i. These final events coincide with the initiation of cell proliferation in VSM cells by PDGF-BB. PMID- 8443873 TI - Single delayed rectifier channels in the membrane of rabbit ventricular myocytes. AB - In rabbit ventricular cells, the delayed rectifier current (IK) has not been extensively studied, and properties of single IK channels still need to be determined. In this study, we present data on a voltage-dependent channel in rabbit ventricular cells; the properties indicate that it is an IK channel. Patch clamp experiments were carried out on cell-attached and inside-out patches of rabbit ventricular cells. Single-channel currents were recorded at negative potentials as inward currents with 150 mM K+ in the pipette. Voltage-dependent channel activity was only present after the return from a depolarizing test pulse, indicating activation on depolarization. Single-channel conductance calculated from the current-voltage relation was 13.1 pS (pooled data, n = 8). The shift in reversal potential of the unitary currents, determined at 150 and 300 mM K+ at the intracellular side of the membrane, showed that the channels were highly permeable to potassium ions. Increase of the duration or the amplitude of the depolarizing test pulse increased channel activity. The time constant for activation at +30 mV was 187 msec (pooled data, n = 4). Half activation potential was -4.9 +/- 3.8 mV (mean +/- SD), and the slope factor was 7.2 +/- 3.7 mV (mean +/- SD). Current tails, reconstructed from averaged single channel currents, revealed that the time course of deactivation decreased from 694 +/- 73 msec at -80 mV to 136 +/- 39 msec at -110 mV. Additional evidence that the channel was indeed an IK channel was provided by the observation that the channel was blocked by 10(-7) M E-4031, a class III antiarrhythmic agent that has been shown to block a component of the macroscopic IK in guinea pig heart. PMID- 8443874 TI - Inhibition of gap junctional conductance by long-chain acylcarnitines and their preferential accumulation in junctional sarcolemma during hypoxia. AB - Electrophysiological and biochemical sequelae of myocardial ischemia occur within minutes of the onset of myocardial ischemia in vivo. Both conduction delay and conduction block occur rapidly within the same time interval as the accumulation of long-chain acylcarnitines. In the present study, double whole-cell voltage clamp procedures were used to assess the influence of long-chain acylcarnitines on gap junctional conductance in isolated pairs of canine ventricular myocytes. Long-chain acylcarnitine (5 microM) decreased gap junctional conductance from 153 to 48 nS in a time-dependent and reversible manner. Although the amplitude of junctional current was reduced by 68%, the current continued to demonstrate a linear current-voltage relation. The extent of endogenous accumulation of long chain acylcarnitines in junctional regions of the sarcolemma was assessed in isolated myocytes in which endogenous free, short-chain, and long-chain acylcarnitine pools had been equilibrated with [3H]carnitine. Under normoxic conditions, long-chain acylcarnitines were not detectable in junctional sarcolemma of myocytes as assessed using electron microscopic autoradiography. Exposure of myocytes to hypoxia (PO2, < 15 mm Hg) for 10 minutes resulted in the preferential accumulation of endogenous long-chain acylcarnitines in junctional sarcolemma (173 +/- 5 x 10(5) molecules/microns 3), a concentration that was sevenfold greater than that found in nonjunctional sarcolemma. Therefore, endogenous long-chain acylcarnitines accumulate preferentially in junctional regions of the sarcolemma during short intervals of hypoxia. Exogenously supplied long-chain acylcarnitines can markedly decrease cellular coupling in a reversible manner, suggesting that this amphiphile may contribute to the marked slowing in conduction velocity in the ischemic heart in vivo, not only by suppressing the rapid Na+ inward current directly, as has been shown previously, but also by decreasing cellular coupling. PMID- 8443875 TI - Background potassium current active during the plateau of the action potential in guinea pig ventricular myocytes. AB - Background outward K+ currents in guinea pig ventricular myocytes were characterized over a broad range of membrane potentials, including those corresponding to the plateau of the action potential. The background current that is blocked by 1 mM Ba2+ (IK,p) activates within 5 msec at positive potentials, does not inactivate, and deactivates very rapidly on repolarization. IK,p is insensitive to Cl- channel blockers, internal or external [Cl-], dihydropyridines, and sulfonylureas. In contrast, the delayed rectifier K+ current (IK) was not completely blocked even by 30 mM Ba2+. Ba(2+)-sensitive current density increased progressively from 0.16 +/- 0.04 pA/pF at 0 mV to 0.52 +/- 0.21 pA/pF at +80 mV (n = 13, mean +/- SEM). The background current remains present when [K+]o is reduced to 0 mM, which suppresses the inward rectifier K+ current (IK1). These and other features suggest that IK,p is generated by K+ channels that are distinct from IK1 or IK. The kinetics and voltage dependence of IK,p render it capable of modulating both the height and duration of the cardiac action potential. PMID- 8443876 TI - Recovery of regional contractile function and oxidative metabolism in stunned myocardium induced by 1-hour circumflex coronary artery stenosis in chronically instrumented dogs. AB - Stunned myocardium produced by 1 hour of critical coronary artery stenosis was evaluated for alteration in regional mechanical function and overall oxidative and fatty acid metabolism by positron emission tomography (PET) in chronically instrumented dogs. Twenty-seven dogs, chronically instrumented for measurements of left ventricular pressure and regional myocardial wall thickening in normal and ischemic zones, were subjected to a 1-hour period of myocardial ischemia produced by graded left circumflex coronary artery stenosis, resulting in minimal residual flow. Mean transmural myocardial flow during 1-hour coronary stenosis decreased to 0.34 +/- 0.04 ml/min per gram in the ischemic zones (normal zone transmural flow, 0.96 +/- 0.10 ml/min per gram). Systolic wall thickening in the ischemic zone was almost completely abolished (-97 +/- 4%). On reperfusion, systolic wall thickening immediately resumed but remained depressed. Progressive recovery was noted with time. At 24 hours, systolic wall thickening was still depressed (-20 +/- 6%, p < 0.01). At 1 week, wall thickening had completely recovered and was no longer significantly different from the control condition. In addition, the absence of necrosis at the site of wall thickness measurements was confirmed at autopsy in all dogs. No abnormalities were found by electron microscopy in four dogs undergoing myocardial biopsies at the time of PET studies. Dynamic PET studies using [1-11C]acetate tracer (performed at 6 hours, 1 week, and 2 weeks after reperfusion) and [1-11C]palmitic acid tracer (performed at 6 hours, 12 hours, 24 hours, 1 week, and 2 weeks after reperfusion) allowed the computation of regional tissue time-activity curves in different regions of interest at different times during follow-up. Despite full reperfusion, abnormal [1-11C]acetate and [1-11C]palmitic acid kinetics were observed in the posterior segments, previously subjected to ischemia, as evidenced by a significant decrease in the slope of the early 11C clearance curve component. Repeat PET studies revealed progressive normalization of overall oxidative metabolism and fatty acid metabolism, which paralleled the time course of recovery of mechanical function. Thus, myocardial ischemia, produced by 1-hour coronary artery stenosis, followed by full reperfusion is associated with a prolonged period of postischemic mechanical and metabolic dysfunction. This transient reduction in oxygen delivery induced a prolonged impairment in fatty acid beta-oxidation as well as a reduction in overall oxidative metabolism despite full reoxygenation. A similar time course for recovery of function and metabolism was observed. PMID- 8443877 TI - Thrombolytic profiles of clot-targeted plasminogen activators. Parameters determining potency and initial and maximal rates. AB - BACKGROUND: Targeting of plasminogen activators to the thrombus by means of fibrin-specific monoclonal antibodies may enhance their thrombolytic potency. The kinetics of clot binding of two human fibrin-specific monoclonal antibodies (MA 12B3 and MA-15C5) and of clot lysis with their chemical 1:1 stoichiometric complexes with recombinant single-chain urokinase-type plasminogen activator (rscu-PA) (rscu-PA/MA-12B3 and rscu-PA/MA-15C5) were determined in hamsters and rabbits. Thrombolytic potencies, maximal rates of clot lysis, and the duration of the lag phases before clot lysis of the antibody/rscu-PA conjugates were compared with those of rscu-PA and tissue-type plasminogen activator (rt-PA). METHODS AND RESULTS: Bolus injection of 7.5 micrograms of 125I-labeled antibody in rabbits with an extracorporeal arteriovenous loop containing a 0.3-mL human plasma clot produced clot-to-blood ratios of 6.6 +/- 1.0 (mean +/- SEM) for MA-12B3 and 1.1 +/- 0.15 for MA-15C5 (p < 0.001 versus MA-12B3) within 6 hours. Progressive digestion of the clot did not alter the binding of MA-12B3 but resulted in as much as a 10-fold increase of the binding of MA-15C5. The conjugates infused intravenously over 90 minutes in hamsters with a human plasma clot in the pulmonary artery produced dose-related in vivo clot lysis. Thrombolytic potencies (maximal slope of the percent lysis versus dose in milligrams of u-PA equivalent per kilogram body weight) were 2,500 +/- 440 for rscu-PA/MA-12B3, 3,600 +/- 640 for rscu-PA/MA-15C5 (p = NS vs. rscu-PA/MA-12B3), 60 +/- 8 for rscu-PA (p < 0.001 versus both conjugates), and 380 +/- 66 for rt-PA (p < 0.001 versus both conjugates). The plasma clearances of the conjugates were fourfold to sixfold slower than those of rscu-PA and rt-PA. Maximal rates of clot lysis, determined by continuous external radioisotope scanning over the thorax, were 0.90 +/- 0.13%, 0.91 +/- 0.17%, 0.84 +/- 0.12%, and 1.1 +/- 0.16% lysis per minute for rscu-PA/MA-12B3, rscu-PA/MA-15C5, rscu-PA, and rt-PA, respectively; these maximal rates were obtained with 0.016, 0.016, 1.0, and 0.25 mg/kg, respectively, and were associated with minimal lag phases of 18 +/- 3.2, 28 +/- 4.9, 34 +/- 3.7, and 25 +/- 3.9 minutes, respectively. CONCLUSIONS: The thrombolytic potency of the rscu-PA/antifibrin conjugates is determined by their clearance, as well as by rate and extent of initial binding to clots and by changes in binding during clot lysis. Clot targeting of rscu-PA with fibrin-specific antibodies increases its thrombolytic potency but does not alter the maximal rate or the minimal lag phase of clot lysis. These parameters appear to be independent of the nature of the plasminogen activator and of targeting. PMID- 8443878 TI - Interruption of vascular thrombus formation and vascular lesion formation by dietary n-3 fatty acids in fish oil in nonhuman primates. AB - BACKGROUND: Because of discrepant claims regarding the relative biological effects of n-3 fatty acids (n-3FAs), we have concurrently measured the effects of dietary n-3FAs on blood and vascular lipid composition, hemostatic function, blood thrombotic responses, vascular thrombus formation, and vascular lesion formation in baboons. METHODS AND RESULTS: Dietary n-3FAs displaced n-6FAs in plasma, platelets, blood vessels, and corresponding urinary eicosanoid metabolites (p < 0.01 in all cases) within weeks after initiation of a semipurified diet containing 1 g/kg per day n-3FA-ethyl ester concentrate (composed of two thirds eicosapentanoic acid and one third docosahexanoic acid). Coincidentally, platelet hemostatic function became minimally impaired (template bleeding times prolonged from 4.3 +/- 0.5 minutes to 7.6 +/- 1.3 minutes, p = 0.039); concentrations of collagen producing half-maximal platelet aggregation increased (from 6.4 +/- 2.1 to 8.5 +/- 2.5 micrograms/mL, p = 0.045); and tissue factor expression by endotoxin-stimulated blood monocytes fell (from 6.5 +/- 1.2 to 1.7 +/- 0.14 mU/10(6) cells, p < 0.005). Dietary n-3FAs decreased deposition of platelets onto thrombogenic segments of Dacron vascular graft incorporated into chronic exteriorized femoral arteriovenous (AV) shunts, a thrombotic process resistant to the effects of both aspirin and heparin (111In-labeled platelet deposition decreased from 14.1 +/- 1.4 x 10(9) platelets/5-cm segment at 40-60 minutes with occlusion to 7.5 +/- 0.8 x 10(9) platelets/5-cm segment without occlusion; p < 0.001). Platelet deposition onto segments of endarterectomized homologous normal aorta in the AV shunts of n-3FA-treated animals was similarly reduced (from 4.4 +/- 0.9 to 1.8 +/- 0.4 x 10(9) platelets; p < 0.01). Dietary n 3FAs interrupted vascular thrombus formation at sites of surgical carotid endarterectomy (platelet deposition, 1.5 +/- 0.4 versus 4.4 +/- 1.0 x 10(9) platelets in untreated controls; p < 0.001). Moreover, endarterectomized aortic segments (EASs) from n-3FA-treated donors exhibited little capacity to induce thrombus formation when tested in the AV shunts of control recipient animals (0.24 +/- 0.10 versus 4.4 +/- 0.90 x 10(9) platelets). However, in the converse crossover experiments, EASs from control animals actively accumulated platelets when studied in the AV shunts of n-3FA-treated animals (1.8 +/- 0.4 x 10(9) platelets; p < 0.01 versus n-3FA-treated EASs in shunts of normal animals). Dietary n-3FAs also abolished vascular lesion formation at sites of carotid endarterectomy 6 weeks after surgery (cross-sectional area of neointima 0.048 +/- 0.031 mm2 compared with 0.428 +/- 0.104 mm2 in control arteries; p = 0.010). CONCLUSIONS: In nonhuman primates, dietary n-3FAs in high doses eliminate both vascular thrombus formation and vascular lesion formation after mechanical vascular injury while largely sparing hemostatic function and modestly reducing blood thrombotic responses. These effects are attributed to selective n-3FA dependent alterations in cellular membrane functions. PMID- 8443879 TI - Why the excess mortality in women after PTCA? PMID- 8443880 TI - Models of effects of low blood cholesterol on the public health. Implications for practice and policy. PMID- 8443881 TI - Myocardial infarction and heart failure. The common ground. PMID- 8443882 TI - Electrocardiographic mapping. Noninvasive electrophysiological cardiac imaging. PMID- 8443883 TI - How should we treat coarctation of the aorta? PMID- 8443884 TI - Unraveling the complex effects of cocaine on the heart. PMID- 8443885 TI - Heat shock proteins and the ischemic heart. An endogenous protective mechanism. PMID- 8443886 TI - A randomized comparison of external and internal cardioversion of chronic atrial fibrillation. PMID- 8443887 TI - Acute reduction of lipoprotein(a) by tissue-type plasminogen activator. PMID- 8443888 TI - Corrected data and analysis of hemodynamic variables influencing plasma endothelin. PMID- 8443889 TI - Risky business: prospective applicability of models. PMID- 8443890 TI - A history of the American Heart Association's Council on Clinical Cardiology. AB - This essay reviews the founding and early history of the Council on Clinical Cardiology of the American Heart Association (AHA), the largest of the AHA's 14 councils. Based on archival research, it stresses the factors that led to the council's formation and shaped its agenda. The council was established in the context of the AHA's transition from a professional society to a voluntary health organization in 1948. But the direct stimulus for its creation was the American College of Cardiology's (ACC) first membership drive 3 years later. When the AHA's Section (later Council) on Clinical Cardiology was formally established in 1952, its official purpose was to "facilitate and encourage investigation, prevention, treatment and education in the field of clinical cardiology." Originally strained, the relations between the AHA and the ACC improved as the organizations came to view each other as potential partners rather than rivals. PMID- 8443891 TI - Vascular biology and medicine in the 1990s: scope, concepts, potentials, and perspectives. PMID- 8443892 TI - Results of percutaneous transluminal coronary angioplasty in women. 1985-1986 National Heart, Lung, and Blood Institute's Coronary Angioplasty Registry. AB - BACKGROUND: The National Heart, Lung, and Blood Institute (NHLBI) Percutaneous Transluminal Coronary Angioplasty (PTCA) 1978-1981 Registry cohort indicated that PTCA risk was higher and efficacy was lower in women. Data from the 1985-1986 PTCA Registry are used to address the question of whether compared with men, women still have a worse outcome after PTCA. METHODS AND RESULTS: The 1985-1986 NHLBI PTCA Registry collected data on consecutive, first-PTCA cases at 16 centers. Initial results are reported for 2,136 patients, 546 of whom were women. Four-year follow-up status was available on 95% of the cohort. Although women were an average of 4.5 years older than the male patients and had more cardiovascular risk factors and more severe angina, their coronary artery disease as assessed by angiography was not more extensive. Rates of angiographic success on a per-lesion basis were similar for women and men (89% versus 88%), and the clinical success rates (79%) were the same. Women had more initial complications (29% versus 20%, p < 0.001) and a considerably higher procedural mortality rate (2.6% versus 0.3%, p < 0.001). For patients who survived the initial procedure, 4 year survival was similar for men and women. At 4 years, women had slightly fewer events (myocardial infarction, repeat PTCA, and/or coronary artery bypass grafting). Despite the higher proportion of women reporting the presence of angina and medication use at 4 years, the proportion reporting improvement in symptomatic status was similar to that of men. CONCLUSIONS: Women undergoing PTCA have a higher procedural mortality risk than men; this is explained in part by their worse cardiovascular risk factor profile. Otherwise, the success rate and long-term prognosis after PTCA are excellent, and PTCA should be considered for women in need of revascularization. PMID- 8443893 TI - Epidemiology of low cholesterol levels in older adults. The Cardiovascular Health Study. AB - BACKGROUND: Low cholesterol levels have been associated with increased mortality from stroke, cancer, and other noncardiovascular diseases, but the reasons for this association remain unclear. One explanation is that persons with low cholesterol levels have early or occult disease that eventually leads to their deaths. METHODS AND RESULTS: This possibility was explored in 2,091 men and 2,714 women 65-100 years old in the Cardiovascular Health Study, a multicenter observational study of risk factors for heart disease and stroke in older adults. Cholesterol levels < or = 160 mg/dL were present in 11.6% of men and 3.7% of women and increased in prevalence with age. After adjustment for age, total cholesterol levels in this range were associated with a twofold increased prevalence of treated diabetes in men and women and with a twofold increased prevalence of cancer diagnosed in the preceding 5 years in women only. Low cholesterol was also associated with lower levels of hemoglobin, albumin, and factor VII, suggesting a link with hepatic synthetic function. On multivariate analysis, factors most strongly associated with low cholesterol levels in men and women were decreased factor VII levels, decreased albumin, and diabetes. CONCLUSIONS: Cross-sectional associations with low cholesterol levels differ by sex and suggest poorer health by some measures. The observed relations with treated diabetes and impaired hepatic synthetic function should be examined for risk of mortality in longitudinal data from this and other observational studies. PMID- 8443894 TI - Radiofrequency catheter ablation of Mahaim fibers at the tricuspid annulus. AB - BACKGROUND: The purpose of this study was to test the feasibility of radiofrequency catheter ablation of Mahaim fibers at the tricuspid annulus. METHODS AND RESULTS: Four patients who fulfilled criteria for having Mahaim fibers and preexcited reciprocating tachycardia underwent radiofrequency catheter ablation. Three patients had atriofascicular connections, and one patient had an atrioventricular connection. The mean age was 27 years (age range, 11-48 years). All patients had highly symptomatic tachycardias, producing syncope in one patient and presyncope in the remaining three patients. Symptoms were present for a mean of 13 years (range, 4-23 years). All pathways conducted only anterogradely, and preexcitation resulted in a left bundle branch block QRS morphology. Adenosine caused block in the accessory pathway in the three patients in whom it was tested. The stimulus to delta interval increased by 75 msec (range, 35-90 msec) during rapid atrial pacing. The atrial insertion of the Mahaim fiber was in the right lateral atrium in one patient, right posterolateral atrium in two patients, and right posterior atrium in one patient. The ventricular insertion was in the distal right bundle branch in three patients and in the posterolateral right ventricle near the tricuspid annulus in the patient with an atrioventricular connection. Stimulus to delta wave mapping was used to help localize the atrial insertion of the atriofascicular connections. A mean of 15 radiofrequency pulses (range, 10-19 pulses) delivered to the tricuspid annulus in the posterior to lateral regions eliminated accessory pathway conduction in all patients. No complications occurred. Tachycardia did not recur during a mean follow-up of 8 months (range, 2-15 months). CONCLUSIONS: Radiofrequency current applied to the tricuspid annulus can safely eliminate tachycardia in patients with Mahaim fibers. PMID- 8443895 TI - Quantitative ultrasonic analysis of myocardium in patients with thalassemia major and iron overload. AB - BACKGROUND: Patients with beta-thalassemia major present with severe anemia and need continuous transfusion therapy. The consequent iron overload leads to hemochromatosis. Initial cardiac dysfunction has been documented even in thalassemics without clinical manifestations of heart failure as well as by conventional echocardiographic-Doppler techniques. The purpose of this study was to assess the acoustic quantitative properties of myocardium in patients with iron overload. METHODS AND RESULTS: Thirty-eight patients with beta-thalassemia major, without clinical signs of cardiac failure, and 20 age- and sex-matched young controls were studied by echocardiography. An on-line analysis of the ultrasonic radiofrequency signal was performed to obtain quantitative operator independent measurements of the integrated backscatter (IB) signal of the ventricular septum and the posterior wall. The integrated values of the radiofrequency signal were normalized for the pericardial interface and expressed in percent (IB%). Thalassemic patients had been receiving transfusion therapy for 16 +/- 5 years and had received 313 +/- 138 transfusion units; they all had received chelation treatment (desferroxiamine) for 9 +/- 2 years. Patients and controls showed comparable values of echocardiographically assessed percent fractional shortening (32 +/- 3% versus 36 +/- 4%, p = NS), whereas thalassemics showed higher values of left ventricular mass index (118 +/- 30 versus 98 +/- 15 g/m2, p < 0.05). The IB% values were higher in patients with thalassemia major than in controls for both septum (35 +/- 14% versus 21 +/- 6%, p < 0.001) and posterior wall (16 +/- 6% versus 11 +/- 3%, p < 0.001). In thalassemic patients, no significant correlation was found between the septum IB% value and hematological parameters, such as the total number of transfusions (r = 0.2, p = NS) or the mean ferritin value (r = 0.1, p = NS). No significant correlation was also found between the septum IB% value and the echocardiographically assessed left ventricular mass index (r = 0.2, p = NS). CONCLUSIONS: These data demonstrate that myocardial reflectivity is abnormally increased in patients with thalassemia major under transfusion treatment, probably due to myocardial iron deposits and/or secondary structural changes. These quantitatively assessed abnormalities in regional reflectivity can be detected when conventional echocardiographic parameters of systolic left ventricular function are undistinguishable from normal controls. PMID- 8443896 TI - Progressive left ventricular dysfunction and remodeling after myocardial infarction. Potential mechanisms and early predictors. AB - BACKGROUND: Left ventricular enlargement and the development of chronic heart failure are potent predictors of survival in patients after myocardial infarction. Prospective studies relating progressive ventricular enlargement in individual patients to global and regional cardiac dysfunction and the onset of late chronic heart failure are not available. It was the aim of this study to define the relation between left ventricular dilatation and global and regional cardiac dysfunction and to identify early predictors of enlargement and chronic heart failure in patients after myocardial infarction. METHODS AND RESULTS: Left ventricular volumes, regional area shrinkage fraction in 18 predefined sectors (gated single photon emission computed tomography), global ejection fraction, and hemodynamics at rest and during exercise (supine bicycle, 50 W, 4 minutes, Swan Ganz catheter) were assessed prospectively 4 days, 4 weeks, 6 months, and 1.5 and 3 years after first myocardial infarction. Seventy patients were assigned to groups with progressive, limited, or no dilatation. Patients without dilatation (n = 38) maintained normal volumes and hemodynamics until 3 years. With limited dilatation (n = 18), left ventricular volume increased up to 4 weeks after infarction and stabilized thereafter; depressed stroke volume was restored 4 weeks after infarction and then remained stable at rest. Wedge pressure during exercise, however, progressively increased. With progressive dilatation (n = 14), depressed cardiac and stroke indexes were also restored by 4 weeks but progressively deteriorated thereafter. Area shrinkage fraction as an estimate of regional left ventricular function in normokinetic sectors at 4 days gradually deteriorated during 3 years, but hypokinetic and dyskinetic sectors remained unchanged. Global ejection fraction fell after 1.5 years, whereas right atrial pressure, wedge pressure, and systemic vascular resistance increased. By multivariate analysis, ejection fraction and stroke index at 4 days, ventriculographic infarct size, infarct location, and Thrombolysis in Myocardial Infarction trial grade of infarct artery perfusion were significant predictors of progressive ventricular enlargement and chronic dysfunction. CONCLUSIONS: Almost 26% of patients may develop limited left ventricular dilatation within 4 weeks after first infarction, which helps to restore cardiac index and stroke index at rest and to preserve exercise performance and therefore remains compensatory. A somewhat smaller group (20%) develops progressive structural left ventricular dilatation, which is compensatory at first, then progresses to noncompensatory dilatation, and finally results in severe global left ventricular dysfunction. In these patients, depression of global ejection fraction probably results from impairment of function of initially normally contracting myocardium. Early predictors from multivariate analysis allow identification of patients at high risk for progressive left ventricular dilatation and chronic ventricular dysfunction within 4 weeks after acute infarction. PMID- 8443897 TI - Infarct artery patency predicts outcome of serial electropharmacological studies in patients with malignant ventricular tachyarrhythmias. AB - BACKGROUND: Surviving myocardial cells near the infarct border zone form the arrhythmogenic substrate for sustained ventricular tachycardia (VT) in humans. Infarct-related artery (IRA) patency may modulate the electrophysiological function of this arrhythmogenic substrate and its response to antiarrhythmic drug therapy. We postulated that effective antiarrhythmic drug therapy selected during serial electrophysiological studies in patients with VT after a myocardial infarction would be identified more frequently when the IRA is patent than when chronically occluded. METHODS AND RESULTS: Consecutive patients (n = 64) with documented coronary artery disease and remote myocardial infarction presenting with spontaneous sustained VT or ventricular fibrillation (VF) were studied. These patients underwent 4 +/- 2 electropharmacological studies identifying effective antiarrhythmic drug therapy in 16 (25%) patients. Drug responders did not differ significantly from nonresponders in demographic, electrocardiographic, angiographic, or hemodynamic measurements. A patent IRA was associated with antiarrhythmic drug response significantly more frequently than was an occluded IRA (45% versus 9%, p = 0.001). Patency of the IRA was the only independent predictor of response to antiarrhythmic drug therapy in this study population. The sensitivity and specificity of using a patent IRA to predict successful drug testing were 81% and 67%, respectively. CONCLUSIONS: The outcome of electropharmacological studies was predicted by the patency of the IRA. A patent IRA was associated with a greater probability of finding effective drug therapy. PMID- 8443898 TI - Body surface potential mapping of ST segment changes in acute myocardial infarction. Implications for ECG enrollment criteria for thrombolytic therapy. AB - BACKGROUND: Several large, randomized clinical trials have shown that early thrombolytic therapy substantially reduces early mortality after acute myocardial infarction (MI). In most trials, eligibility criteria include typical chest pain and diagnostic ST segment elevation in two or more contiguous leads of the standard 12-lead ECG. Unfortunately, large areas of the thoracic surface are left unexplored by the standard electrode positions. As a consequence, acute MI patients with ST elevation in regions not interrogated by the conventional electrodes may not receive reperfusion therapy and its attendant benefits. METHODS AND RESULTS: The present study compares 120-lead body surface potential map (BSPM) data from 131 patients with acute MI and 159 normal control subjects (N). The MI population was stratified according to the location of ventricular wall motion abnormalities evidenced by radionuclide imaging into 76 patients with anterior MI (AMI), 32 patients with inferior MI (IMI), and 23 patients with posterior MI (PMI). BSPM were recorded within 24 hours of admission. Group mean BSPM of the ST segment were obtained for N, AMI, IMI, and PMI by sampling the time-normalized ST-T waveform at 18 equal intervals and averaging the voltages at each electrode site over the first five of these 18 ST-T time instants. Corresponding discriminant maps were also computed for each pairwise comparison (AMI versus N, IMI versus N, and PMI versus N) by subtracting the normal group mean voltages from each MI group mean voltages and by further dividing each resulting difference by the composite standard deviation calculated from the pooled groups. Discriminant analysis for each bigroup classification was also performed using as measurements the ST magnitudes in 120 electrode sites from each individual. Finally, the number of patients in each MI group with ST changes outside the 95% normal range was calculated for each electrode position. The following results were obtained: 1) In each MI group, ST depression departs more significantly from normal values than ST elevation. 2) The most significant ST changes (both ST elevation and ST depression) are observed in IMI, the least significant in AMI. 3) For each pairwise comparison, measurements from two lead sites are entered into the stepwise discriminant procedure: the first measurement is ST depression, the second ST elevation. Classification rates are 82% for AMI, 93% for PMI, and 100% for IMI at a specificity level of 95%. 4) From the six leads selected for optimal classification of the three MI groups, five are outside the area sampled by the conventional precordial electrodes. 5) The use of site-dependent thresholds for ST measurements based on 95% normal range yields the best compromise between sensitivity and specificity. A fixed threshold of 1 mm for ST elevation or ST depression produces increased sensitivity in AMI at the cost of marked loss in specificity and reduces sensitivity in both IMI and PMI with no benefit in specificity. CONCLUSIONS: Analysis of BSPM identifies areas on the torso where the most significant ST changes most frequently occur in acute MI. Two leads from areas with the most abnormal ST changes achieve optimal classification in each MI class. Of these six leads, five are outside the standard precordial lead positions. ST depression is the most potent discriminator for each MI group and contains information independent from ST elevation. Quantitative analysis of ST magnitude at each electrode site allows determination of best thresholds for ECG criteria. Appropriate selection of ECG leads may help remove inconsistencies in current ECG selection criteria and improve comparability of treatment results. PMID- 8443899 TI - Differential effects of isoproterenol on sustained ventricular tachycardia before and during procainamide and quinidine antiarrhythmic drug therapy. AB - BACKGROUND: Autonomic modulation, especially increased sympathetic activity may play a role in the genesis of ventricular arrhythmias. The purpose of this study was to determine whether beta-sympathetic stimulation with isoproterenol would alter sustained ventricular tachycardia (VT) circuits similarly during the drug free and antiarrhythmic drug-treated states. METHODS AND RESULTS: Twenty-five patients with repeatedly inducible, hemodynamically stable, sustained VT were evaluated by programmed ventricular stimulation. In the antiarrhythmic drug-free state, isoproterenol (0.03 microgram/kg per minute) shortened the following intervals (in milliseconds; mean +/- SEM; 25 patients; paired t test): sinus cycle length (792 +/- 37 to 568 +/- 18; (p < 0.001), ventricular paced QT interval (386 +/- 8 to 348 +/- 6; p < 0.001), ventricular paced QRS duration (185 +/- 4 to 182 +/- 4; p = 0.014), ventricular effective (238 +/- 5 to 208 +/- 4; p < 0.001) and functional (261 +/- 6 to 227 +/- 5; p < 0.001) refractory periods, and the VT cycle length (VTCL) (311 +/- 9 to 291 +/- 9; p < 0.001). Isoproterenol (0.03 microgram/kg per minute) was administered during 31 antiarrhythmic drug trials (procainamide, n = 18; quinidine, n = 13) in 22 patients. Isoproterenol shortened the sinus cycle length, QT interval during ventricular pacing, and ventricular effective and functional refractory periods before and during procainamide and quinidine therapy (ANOVA; isoproterenol effect, p < or = 0.0002 for all). The amount of decrease in these intervals with isoproterenol was the same before and during procainamide and quinidine therapy (ANOVA interaction, p = NS for all). The QRS duration during ventricular pacing and VTCL were also shortened by isoproterenol before and during procainamide (baseline, n = 17; QRS, 182 +/- 4 to 178 +/- 4 msec; VTCL, n = 18, 314 +/- 11 to 291 +/- 11 msec; during procainamide, QRS, 218 +/- 7 to 197 +/- 6 msec; VTCL, 422 +/- 15 to 359 +/- 11 msec) and quinidine (baseline, n = 13; QRS, 190 +/- 6 to 185 +/- 5 msec; VTCL, n = 12, 298 +/- 10 to 280 +/- 9 msec; during quinidine, QRS, 223 +/- 9 to 208 +/- 8 msec; VTCL, 415 +/- 14 to 355 +/- 10 msec) (isoproterenol effect p < or = 0.0003 for all). However, the amount of decrease in QRS duration and VTCL with isoproterenol was greater during procainamide and quinidine than in the drug-free state (ANOVA interaction, p < or = 0.02 for all). These changes continued to be significant when normalized for the initial QRS duration and VTCL (p < or = 0.03 for all). CONCLUSIONS: Isoproterenol affects presumed reentrant sustained VT circuits less in the absence of antiarrhythmic drugs but markedly attenuates the antiarrhythmic drug-induced slowing of sustained VT. To the extent that the change in QRS duration reflects a change in conduction within the VT circuit, these data imply that the attenuation of drug-induced slowing of VT by isoproterenol is due to a greater change in conduction rather than refractoriness. PMID- 8443900 TI - Comparison of angioplasty and surgery for unoperated coarctation of the aorta. AB - BACKGROUND: The use of balloon coarctation angioplasty instead of surgery as treatment for unoperated coarctation of the aorta is controversial. The efficacy and complications of the two procedures have not been studied before in a prospective fashion. METHODS AND RESULTS: Thirty-six patients were prospectively randomized to either angioplasty (20 patients) or surgery (16 patients). Immediate results and patient follow-up, including physical examination, angiograms, and magnetic resonance imaging, were compared between groups. Reduction in peak systolic pressure gradient across the coarctation was similar (86%) immediately after both balloon coarctation angioplasty and surgery. On follow-up, aneurysms were seen only in the angioplasty group (20%) and not in the surgery group (0%). No aneurysms have shown progression or required surgery. The incidence of other complications was similar in both groups, although two patients experienced neurological complications after surgery. Although not statistically different, the incidence of restenosis (peak systolic pressure gradient > or = 20 mm Hg) tended to be greater in the angioplasty group (25%) than in the surgery group (6%). Restenosis after angioplasty occurred more frequently in patients with an aortic isthmus/descending aorta diameter ratio < 0.65 and was associated with an immediate catheterization residual peak systolic pressure gradient across the coarctation > or = 12 mm Hg. CONCLUSIONS: Immediate gradient reduction is similar after balloon coarctation angioplasty and surgical treatment of unoperated coarctation of the aorta. The risks of aneurysm formation and possibly restenosis after angioplasty are higher than after surgery, although the risks of other complications are similar. Balloon coarctation angioplasty may provide an effective initial alternative to surgical repair of unoperated coarctation of the aorta in children beyond infancy, particularly in patients with a well-developed isthmus. Further follow-up is necessary to determine the long-term risks of postangioplasty aneurysms. PMID- 8443901 TI - Sudden cardiac death and the use of implantable cardioverter-defibrillators in pediatric patients. The Pediatric Electrophysiology Society. AB - BACKGROUND: During the past decade, the implantable cardioverter-defibrillator (ICD) has emerged as the primary therapeutic option for survivors of sudden cardiac death (SCD). Investigation of the clinical efficacy of these devices has primarily assessed outcome in adults with coronary artery disease. The purpose of this cooperative, international study was to evaluate the impact of ICDs on the pediatric population of SCD survivors, based on an analysis of the clinical characteristics and outcomes of young patients who underwent ICD implantation following an episode of life-threatening ventricular tachycardia or resuscitation from SCD. METHODS AND RESULTS: An initial data base, established by contacting the manufacturers of the various commercially and investigationally available devices, identified 177 patients who were less than 20 years of age at the time of initial implantation of an ICD. With this data base as a reference, detailed responses were subsequently obtained from physicians involved in the care of 125 (71%) of these patients. The patients ranged in age from 1.9 to 19.9 years (mean, 14.5 +/- 4 years) and weighted 9.7-117 kg (mean, 44.6 +/- 14 kg). Of the 125 patients, 76% were survivors of SCD, 10% had drug refractory ventricular tachycardia, and 10% had syncope with heart disease and inducible sustained ventricular tachyarrhythmias. The most common types of associated cardiovascular disease were hypertrophic and dilated cardiomyopathies (54%), primary electrical diseases (26%), and congenital heart defects (18%). Ventricular function was abnormal in 46% of the patients. During a mean follow-up of 31 +/- 23 months, at least one ICD discharge occurred in 85 of the 125 (68%) patients. Seventy-three patients (59%) received at least one appropriate ICD discharge, and 25 patients (20%) had one or more spurious or indeterminate discharges. Duration of follow-up > 24 months (p = 0.001) and inducibility of a sustained ventricular arrhythmia (p = 0.05) were correlated with appropriate ICD discharges. There were nine deaths during the study period: five sudden, two due to recurrent ventricular arrhythmias, and two related to congestive heart failure. Abnormal ventricular function (p = 0.002) and prior ICD discharge (p = 0.01) were univariate correlates of patient mortality; by multivariate logistic regression, abnormal ventricular function was the only significant correlate of death (p = 0.005). By actuarial analysis, the estimated overall post-ICD implant survival rates at 1, 2, and 5 years were 95%, 93%, and 85%, respectively. The corresponding sudden death-free survival rates were 97%, 95%, and 90%. CONCLUSIONS: Pediatric patients resuscitated from SCD appear to remain at risk for recurrence of life-threatening tachyarrhythmias. During a mean follow-up of 31 months, the ICD provided an effective therapy for such arrhythmias in the majority of patients in this study. Following ICD implant, impaired ventricular function was the primary factor correlated with mortality. The patterns of ICD discharge observed in young patients and, thus, inferred risk of recurrent life threatening arrhythmias are similar to those of adult survivors of SCD. Thus, the use of ICDs in pediatric patients, with implant selection criteria similar to adults, appears valid. PMID- 8443902 TI - A predictive method for estimating the late angiographic results of coronary intervention despite incomplete ascertainment. AB - BACKGROUND: Investigations of coronary restenosis typically use late (4-6-month) angiographic end points. Since only 50-80% of patients generally undergo repeat angiography, however, restenosis for the population as a whole is usually estimated by assuming that nonrestudied and restudied patients are similar. If restudied and nonrestudied patients differ, incomplete angiographic follow-up can yield an erroneous estimate of restenosis. No suitable method has yet been devised to detect and correct these errors. METHODS AND RESULTS: We studied the clinical indications for angiographic restudy in an actual series of 301 treated lesions in 267 consecutive patients who underwent either Palmaz-Schatz stenting (126 patients) or directional coronary atherectomy (141 patients) at our institution. While only 249 (83%) treated segments underwent 4-6-month angiographic follow-up, all had clinical follow-up that described whether specific indications for restudy were present. Patients who had no clinical indications for such restudy were designated as having elective follow-up. In contrast, patients who had recurrent symptoms or positive exercise studies and were scheduled for repeat angiography at the independent recommendation of their referring cardiologist were designated as having nonelective follow-up. Mean late percent stenosis or binary restenosis rate (> 50% diameter stenosis) was determined for elective versus nonelective lesions that underwent follow-up angiography. These values were then used to input the behavior of the nonrestudied lesions according to their clinical status. From these imputations, a "predictive" model was developed to estimate the mean restenosis values that would have been found had the entire population actually undergone angiographic follow-up. Comparisons between the estimates of this predictive method and the traditional method that uses only the actual angiographic data demonstrate how alterations in various parameters influence the selection bias caused by incomplete angiographic follow-up. Of the 301 lesions available for follow-up, 100 of the 103 (97%) nonelective versus 149 of the 198 (75%, p < 0.001) elective lesions actually underwent angiographic follow-up. Mean follow-up percent stenosis (50% versus 27%) and the binary restenosis rate (53% versus 13%) differed significantly for the nonelective versus the elective lesions, respectively (both p < 0.001). Even at the fairly high (83%) angiographic follow up rate, elective versus nonelective status was thus a confounder that caused differences between the restenosis rate estimated by the traditional (29.1%; 95% CI: 23.4, 34.7) and the predictive methods (26.3%; 95% CI: 21.4, 31.1). Larger (and even statistically significant) differences may be present under the conditions that exist in many current studies. CONCLUSIONS: Restenosis trials with < 90% angiographic follow-up suffer from selection bias. Traditional methods that analyze only the restudied patients fail to correct for the important confounding influence of the clinical status of the nonrestudied patients. By using this readily available clinical information about the nonrestudied patients, a predictive method may be developed that provides a closer estimate of the true restenosis behavior for the population as a whole. PMID- 8443903 TI - Long-term clinical follow-up in patients with angiographic restudy after successful angioplasty. AB - BACKGROUND: Restenosis remains a critical limitation after coronary angioplasty. There is little information comparing long-term prognosis in patients who suffer from restenosis and others who do not. The purpose of this paper is to determine the clinical events in patients with restenosis or continued patency documented by restudy coronary arteriography. METHODS AND RESULTS: The source of data was the clinical data base at Emory University. Patients who had previous coronary surgery and patients who underwent angioplasty in the setting of acute myocardial infarction were excluded. A total of 3,363 patients undergoing angiographic restudy 4 months to 1 year after angioplasty were compared with 3,858 not undergoing restudy. In the restudy population, 1,570 had restenosis and 1,793 had patent arteries at all sites dilated. The restenosis patients were older and had more hypertension, more diabetes, more severe angina, more multivessel coronary artery disease, more severe stenoses, and less satisfactory original results. At restudy, in patients without restenosis, 38.7% had angina versus 70.7% in patients with restenosis (p < 0.0001). There were few deaths in the first 6 months. At 6 years, the survival rate was 0.95 without restenosis and 0.93 with restenosis (p = 0.16). At 6 months and 6 years, freedom from myocardial infarction was 0.97 and 0.88 without restenosis and 0.93 and 0.85 with restenosis (p = 0.0001). On multivariate analysis, restenosis was an independent correlate of myocardial infarction but not mortality. At 6 months and 6 years, freedom from coronary bypass surgery was 0.99 and 0.94 without restenosis and 0.91 and 0.78 with restenosis (p < 0.0001). At 6 months and 6 years, freedom from repeat angioplasty was 0.96 and 0.76 without restenosis and 0.44 and 0.20 with restenosis (p = 0.0001). The highest event rates were noted in the patients with restenosis with recurrent chest pain. Patients not undergoing restudy differed somewhat from the study group, and there were far fewer repeat revascularization procedures in the group not undergoing restudy. CONCLUSIONS: Patients with restenosis are more likely to have recurrent angina pectoris. Although there is no or little difference in survival, there is a difference in myocardial infarction rate in the patients with and without restenosis. The low myocardial infarction and death rates in the group suffering restenosis may be related to repeat revascularization in these patients; the principal events in the restenosis population are frequent repeat revascularization procedures. PMID- 8443904 TI - Quantitative Doppler assessment of valvular regurgitation. AB - BACKGROUND: Quantitation of valvular regurgitation remains a challenge. The accuracy of quantitative Doppler is controversial, and its ability to measure regurgitant volume is unknown; therefore, it is not widely used. METHODS AND RESULTS: In 120 patients (20 without regurgitation, 19 with aortic regurgitation, and 81 with mitral regurgitation), the stroke volume through the mitral annulus and left ventricular outflow tract were measured using pulsed-wave Doppler concurrently with left ventricular stroke volume calculated using left ventricular volumes measured by two-dimensional echocardiography Simpson's biapical method. Regurgitant volume and fraction were thus computed using Doppler or ventricular methods. In normal patients there were good correlations between Doppler and left ventricular measurements of stroke volume. Doppler regurgitant volume and fraction were 4.4 +/- 4.4 mL and 5.3 +/- 4.5%, respectively. In patients with aortic regurgitation, there were good correlations between Doppler and left ventricular measurements of stroke volume, regurgitant volume, and regurgitant fraction (r = 0.97, r = 0.95, and r = 0.93, respectively; p < 0.0001). In patients with mitral regurgitation, despite good correlations between Doppler and ventricular methods for stroke volume, regurgitant volume, and regurgitant fraction (r = 0.94, r = 0.93, and r = 0.94, respectively; p < 0.001), these variables were overestimated by Doppler. However, in the last 54 patients compared with the first 27, overestimation decreased significantly for regurgitant volume (5 +/- 10 mL versus 18 +/- 27 mL, p < 0.05) and regurgitant fraction (3.3 +/- 6.7% versus 6.2 +/- 6.8%, p = 0.05). CONCLUSIONS: Quantitative Doppler can be performed in large numbers of patients in a clinical laboratory. Its potential limitation was identified as overestimation of mitral regurgitation, which is overcome with increased experience. Its achieved accuracy in mitral and aortic regurgitation allows measurement not only of regurgitant fraction but most importantly of regurgitant volume. PMID- 8443905 TI - Abnormal baroreceptor-mediated vasodilation of the peripheral circulation in congestive heart failure secondary to idiopathic dilated cardiomyopathy. AB - BACKGROUND: Peripheral edema is a major clinical problem in congestive heart failure (CHF). The function of the edema-protective baroreceptor-mediated and local nervous vasoconstrictor reflexes of the lower leg during orthostasis in moderate and severe CHF has largely been unexplored. METHODS AND RESULTS: Baroreceptor-mediated and local nervous regulation of subcutaneous blood flow of the lower leg was studied in healthy subjects and in patients with moderate and severe CHF secondary to idiopathic dilated cardiomyopathy. Blood flow was measured by the local 133Xe washout method in the supine position and during 45 degrees head-up tilt. When the central baroreceptor reflex alone was activated, the changes in subcutaneous blood flow of the heart failure patients in both groups were significantly different from those of the eleven control subjects: blood flow increased 48 +/- 26% in 10 severe and 3 +/- 24% in nine moderate CHF patients compared with the decrease in blood flow of -36 +/- 15% observed in 11 control subjects (p < 0.0001 for both). A highly significant direct association was demonstrated between changes in blood flow and New York Heart Association functional class (p = 0.007) and the left ventricular ejection fraction (p = 0.01). Activation of the baroreceptor and local venoarteriolar axon reflexes simultaneously increased blood flow significantly (30 +/- 9%) in 14 patients with severe CHF, compared with the decrease found in 14 control subjects (-53 +/- 9%) and in the group of 14 patients with moderate CHF (-17 +/- 25%) (p < 0.0001 for both). CONCLUSIONS: Patients with CHF secondary to idiopathic dilated cardiomyopathy have an abnormal baroreceptor-mediated vasodilation in subcutaneous tissue of the lower leg during the upright position, which increases with the severity of the disease. The hemodynamic consequence is capillary hypertension and hyperemia in the leg during the upright position that may contribute to the development of edema and to the initiation of structural changes (microangiopathy) demonstrated in the microcirculation. PMID- 8443906 TI - Signal-averaged electrocardiogram. Improved identification of patients with ventricular tachycardia using a 28-lead optimal array. AB - BACKGROUND: Although the signal-averaged ECG (SAECG) is currently the best noninvasive test to identify patients with ventricular tachycardia (VT) following myocardial infarction (MI), it is still a relatively insensitive test. Body surface mapping has improved the sensitivity of ECG in detecting various cardiac diseases. This study applied body surface mapping to the SAECG in the form of a clinically practical, 28-lead optimal array and compared its sensitivity and specificity with those of an orthogonal array. METHODS AND RESULTS: Two hundred twenty-three patients with previous MI (82 with inducible VT) underwent SAECG using 28 surface electrodes from which were obtained a three-lead orthogonal array and a 28-lead optimal array (optimal). From the orthogonal array, two QRS durations (QRSd) were obtained using the combined vector magnitude method (CVM) and the earliest onset to latest offset of the three individually filtered leads (individual). From the optimal array, 28 QRSd were obtained, each defined as the duration from the earliest onset of any of the 28 leads to the offset of each individually filtered lead. QRSd > 120 msec in > or = 3 leads was considered abnormal. For CVM and individual, QRSd of > 120 msec were considered abnormal. While the specificity of each method was comparable (84%, 86%, and 84% for CVM, individual, and optimal, respectively), the sensitivity of optimal (70%) was significantly greater than the sensitivity of CVM (54%) (p = 0.001) or individual (59%) (p = 0.004). The magnitude of improvement in sensitivity, 16% and 15%, respectively, was equal for anterior (n = 120) and inferior (n = 103) infarctions. CONCLUSIONS: Body surface mapping using the 28-lead optimal array significantly improved the sensitivity of the SAECG without loss of specificity. The increased sensitivity was of equal magnitude for inferior and anterior infarctions. The superiority and practicality of the 28-lead optimal array make it worth pursuing as an option for further refinement in SAECG: PMID- 8443907 TI - A population study of the natural history of Wolff-Parkinson-White syndrome in Olmsted County, Minnesota, 1953-1989. AB - BACKGROUND: Virtually all natural history studies of Wolff-Parkinson-White (WPW) syndrome have been case series and, as such, have been constrained by referral biases, skewed age and sex distributions, or brief follow-up periods. The purpose of our study was to examine the natural history, the development of arrhythmias, and the incidence of sudden death in an entire cohort of pediatric and adult WPW patients from a community-based local population. METHODS AND RESULTS: We identified 113 residents of Olmsted County, Minnesota, during the period 1953 1989 using the centralized records-linkage system provided by the Mayo Clinic and the Rochester Epidemiology Program Project. Medical records and ECGs were reviewed to confirm the diagnosis and to establish pathway location by ECG criteria. Follow-up, via record review and telephone interview, was complete in 95% of subjects through 1990. The incidence of newly diagnosed cases was approximately four per 100,000 per year. Preexcitation was not present on the initial ECG of 22% of the cohort. Approximately 50% of the population was asymptomatic at diagnosis, with 30% subsequently having symptoms related to arrhythmia at follow-up. Two sudden cardiac deaths (SCD) occurred over 1,338 patient-years of follow-up, yielding an overall SCD rate of 0.0015 (95% confidence interval, 0.0002-0.0054) per patient-year. No SCD occurred in patients asymptomatic at diagnosis. CONCLUSIONS: The incidence of sudden death in a local community-based population is low and suggests that electrophysiological testing should not be performed routinely in asymptomatic patients with WPW syndrome. Nevertheless, young, asymptomatic patients, particularly those < 40 years old, should return for medical follow-up should symptoms develop. PMID- 8443908 TI - Interaction between thromboxane A2 and 5-hydroxytryptamine receptor subtypes in human coronary arteries. AB - BACKGROUND: Platelets release two powerful vasoconstrictors--thromboxane A2 (TXA2) and 5-hydroxytryptamine (5-HT). Animal studies have suggested that these two substances may act in a synergistic fashion to stimulate platelet activity and smooth muscle vasoconstriction. METHODS AND RESULTS: To assess the interaction between TXA2 and 5-HT at the individual 5-HT receptor subtypes reported to mediate contraction, the effect of the amine was determined in the presence of differing concentrations of the thromboxane mimetic U46619. A total of 168 vessel segments were removed from 20 recipient hearts of patients undergoing cardiac transplantation. Segments were set up in isolated organ baths and tested for their response to 5-HT in the presence of an EC10, EC30, or EC50 concentration of U46619 (n = 4). A synergistic response was only seen in a small number of the segments tested under these conditions. However, in the presence of ketanserin (10(-6) M) to block 5-HT2 receptors, there was a significant increase in the response to 10(-6) M 5-HT in the presence of both the EC30 (p < 0.025) and EC50 (p < 0.05) concentrations of U46619 (n = 4). The potentiation of non-5-HT2 receptor mediated responses to 5-HT, in the presence of U46619 (EC30), could be prevented by 10(-7) M methiothepin, a nonselective 5-HT1-like/5-HT2 receptor antagonist. CONCLUSIONS: These data indicate that TXA2 receptor activation can increase the response of 5-HT mediated by 5-HT1-like receptors in human coronary arteries. 5-HT1-like receptors have been shown to mediate the contractile effect of 5-HT in patients with variant and chronic stable angina. Thus, platelet contents may act together at specific receptor subtypes in the induction of myocardial ischemia. PMID- 8443909 TI - Loss of myocardial protection after preconditioning correlates with the time course of glycogen recovery within the preconditioned segment. AB - BACKGROUND: Although previous investigators have demonstrated that myocardial preconditioning reduces infarct size, the mechanisms of cardioprotection associated with preconditioning are not completely understood. METHODS AND RESULTS: To test the hypothesis that preconditioning (four 5-minute episodes of ischemia each followed by 5 minutes of reperfusion) reduces infarct size by depleting cardiac glycogen stores and attenuating the degree of intracellular acidosis during subsequent prolonged left coronary artery occlusion, preconditioned and control rats were subjected to 45 minutes of left coronary artery occlusion and 120 minutes of reflow immediately after preconditioning (groups 1P and 1C, respectively) or after 30 minutes (groups 2P+30m and 2C), 1 hour (groups 3P+60m and 3C), or 6 hours (groups 4P+360m and 4C) of nonischemic recovery after preconditioning but before prolonged ischemia. In each group, cardiectomy was performed in selected rats immediately before prolonged ischemia for cardiac glycogen assay. In selected animals, 31P magnetic resonance spectroscopy was performed to monitor intracellular pH and measure high-energy phosphate levels during ischemia and reperfusion. Group 1P rats demonstrated marked glycogen depletion after preconditioning compared with controls (0.72 +/- 0.39 [n = 9] versus 5.67 +/- 1.73 [n = 12] mg glucose/g wet wt; p < 0.001 versus group 1C) that was associated with attenuation of intracellular acidosis during ischemia, as measured by 31P magnetic resonance spectroscopy (6.8 +/- 0.3 [n = 11] versus 6.2 +/- 0.3 [n = 9] pH units; p < 0.01), and marked infarct size reduction (0.3 +/- 0.6% [n = 7] versus 38.1 +/- 11.3% [n = 7], infarct size divided by risk area; p < 0.0001). During ischemia, there were no differences in myocardial ATP or phosphocreatine levels or in any hemodynamic determinant of myocardial oxygen demand between groups 1P and 1C. In preconditioned rats that were allowed to recover before ischemia (groups 2P+30m, 3P+60m, and 4P+360m), the time course of glycogen repletion paralleled the loss of protection from ischemic injury. CONCLUSIONS: Glycogen depletion and the attenuation of intracellular acidosis during ischemia appear to be important factors in delaying irreversible injury and reducing infarct size in this animal model of myocardial preconditioning. PMID- 8443910 TI - Adenosine alters glucose use during ischemia and reperfusion in isolated rat hearts. AB - BACKGROUND: Adenosine possesses marked cardioprotective properties, but the mechanisms for this beneficial effect are unclear. The objective of this study was to determine the effect of adenosine given before ischemia or at reperfusion on mechanical function, glucose oxidation, glycolysis, and metabolite levels in isolated, paced (280 beats per minute) working rat hearts. METHODS AND RESULTS: Hearts were perfused with Krebs-Henseleit buffer containing 11 mM glucose, 1.2 mM palmitate, and 500 microU.mL-1 insulin at an 11.5 mm Hg left atrial preload and 80 mm Hg aortic afterload. Adenosine (100 microM) pretreatment or adenosine (100 microM) at reperfusion markedly increased the recovery of mechanical function (from 44% to 81% and 96%, respectively) after 60 minutes of low-flow ischemia (coronary flow, 0.5 mL.min-1). Glucose oxidation (mumol.min-1 x g dry wt-1) was inhibited during ischemia (from 0.44 +/- 0.04 to 0.12 +/- 0.01), and this was not altered by adenosine (100 microM). During reperfusion, glucose oxidation recovered (to 0.38 +/- 0.02) and adenosine (100 microM), given at reperfusion, further increased glucose oxidation (to 0.52 +/- 0.06). The rate of glycolysis (mumol.min-1 x g dry wt-1), which was unaffected by ischemia per se, was inhibited by adenosine pretreatment (from 4.7 +/- 0.3 to 2.6 +/- 0.3). During reperfusion, glycolysis was also inhibited by adenosine relative to control (3.9 +/- 0.8) either when present during ischemia (2.6 +/- 0.6) or during reperfusion (1.4 +/- 0.4). These effects of adenosine on glucose metabolism reduced the calculated rate of H+ production attributable to glucose metabolism during the ischemic and reperfusion periods. Tissue lactate levels (mumol.g dry wt-1), which increased during ischemia (from 9.3 +/- 1.1 to 87.4 +/- 10.3) and then declined during reperfusion (to 26.2 +/- 3.7), were depressed further by adenosine pretreatment (to 19.7 +/- 4.1) and by adenosine at reperfusion (to 13.6 +/- 2.1). ATP levels (mumol.g dry wt-1), which were depressed by ischemia (from 18.1 +/- 1.1 to 10.6 +/- 1.3) and tended to be further depressed during reperfusion (to 7.1 +/- 0.7), were increased by adenosine pretreatment (to 14.1 +/- 1.2) and by adenosine at reperfusion (to 15.6 +/- 2.4). CONCLUSIONS: The effects of adenosine on glucose metabolism that would tend to decrease cellular acidosis and hence, Ca2+ overload, may explain the beneficial effects of adenosine on mechanical function observed in these hearts during reperfusion after ischemia. PMID- 8443911 TI - Interstitial dendritic cells of the rat heart. Quantitative and ultrastructural changes in experimental myocardial infarction. AB - BACKGROUND: This study was undertaken to investigate the qualitative and quantitative changes that interstitial dendritic cells (IDC) of the heart undergo during the time course of experimental myocardial infarction. METHODS AND RESULTS: Left coronary arterial ligations were performed in 43 rats that were killed 2, 4, 7, 14, and 21 days after surgery. Thirteen unoperated and 39 sham operated rats were used as controls. Frozen sections were stained with monoclonal antibodies (OX 6 and W3/25) to identify and count IDC by light microscopy. Immunoelectron microscopy was also used to identify IDC. The number of IDC per mm2 of tissue section was calculated for all hearts. In hearts with myocardial infarction, IDC were counted in three areas: the center of the myocardial infarction, the border zone, and the noninfarcted left ventricle. In OX 6 antibody-stained preparations, the number of IDC per mm2 was 82 +/- 10 in the left ventricle of unoperated rats. Hearts with myocardial infarction showed marked increases in the numbers of IDC per mm2 in the border zone (796 +/- 79 at 7 days and 528 +/- 98 at 14 days). In the border zone, IDC often were associated with small clusters of T-helper lymphocytes, which reacted with W3/25 antibody (the rat homologue of human CD4). The center of the myocardial infarction showed an increase in IDC only on day 7 (120 +/- 18). By 21 days, IDC in the border zone were only slightly increased (159 +/- 15). CONCLUSIONS: These findings suggest that IDC migrate to the myocardial infarction border zone. They participate in the activation of lymphocytes and in the initiation of immune responses and decrease in number as inflammation subsides and scarring develops. PMID- 8443912 TI - The renin-angiotensin system and volume overload-induced cardiac hypertrophy in rats. Effects of angiotensin converting enzyme inhibitor versus angiotensin II receptor blocker. AB - BACKGROUND: The degree of cardiac hypertrophy is not only load dependent: Among other factors, the renin-angiotensin system may play a role in the regulation of cardiac myocyte growth. METHODS AND RESULTS: To evaluate the role of the renin angiotensin system in volume overload-induced cardiac hypertrophy, we assessed: 1) the time course of changes in cardiac hemodynamics, cardiac anatomy, and plasma and cardiac renin activity in response to volume overload induced by two sizes of abdominal aortocaval shunt and 2) the effects of chronic treatment with an angiotensin converting enzyme inhibitor (ACEI) versus an angiotensin II receptor blocker on hemodynamics and cardiac hypertrophy. Drug treatment started 3 days before shunt surgery. An increase in left ventricular end-diastolic pressure (LVEDP) and the development of right ventricular (RV) and left ventricular (LV) eccentric hypertrophy in response to volume overload occurred within the first week after induction of the shunt. Plasma renin activity (PRA) and cardiac renin activity peaked shortly after induction of the shunt. During the chronic phase, LVEDP and PRA decreased somewhat but remained significantly elevated up to 7 weeks after shunt surgery. Cardiac renin activity returned toward normal within 4 weeks after surgery. Treatment with the ACEI enalapril caused only a modest decrease in LV internal diameter but did not affect increases in LV and RV weights in response to volume overload despite a major decrease in LVEDP after chronic treatment. In contrast, treatment with the angiotensin II receptor blocker losartan, which had similar effects on cardiac and peripheral hemodynamics, prevented dilation of the LV after 7 days and attenuated the dilation of the LV after 28 days. Moreover, increases in LV and RV weights were significantly attenuated by losartan. CONCLUSIONS: The development of volume overload-induced cardiac hypertrophy is associated with significant increases in PRA and cardiac renin activity shortly after induction of an aortocaval shunt. Whereas the two blockers of the renin-angiotensin system decreased LVEDP to a similar extent, only the angiotensin II receptor blocker blunted the hypertrophic response of the heart to volume overload, which is indicative for other than hemodynamic determinants of the cardiac hypertrophic response. One trophic factor may be cardiac angiotensin II generated via an angiotensin II-forming enzyme resistant to ACEI and possibly activated by cardiac volume overload. PMID- 8443913 TI - Cholinergic modulation of the coronary vasoconstriction induced by cocaine in conscious dogs. AB - BACKGROUND: The effects of cocaine on the coronary circulation were examined in conscious dogs chronically instrumented to measure arterial and left ventricular pressures, coronary blood flow, and arterial and coronary sinus oxygen content. METHODS AND RESULTS: With heart rate held constant, the peak effects of cocaine (1 mg/kg i.v.) occurred within 2 minutes, when mean arterial pressure increased by 42 +/- 5 mm Hg, coronary blood flow increased by 13 +/- 3%, and coronary vascular resistance increased by 24 +/- 3%. The arterial oxygen content increased significantly (by 2.8 +/- 0.3 vol%), the arterial-coronary sinus oxygen difference increased by 2.5 +/- 0.6 vol%, and myocardial oxygen consumption increased by 41 +/- 9%. The increase in coronary vascular resistance induced by cocaine was attenuated (p < 0.05) in the presence of cholinergic blockade (12 +/- 3%) despite a similar increase in MVO2 (49 +/- 8%). The increase in coronary vascular resistance was enhanced (p < 0.05) in the presence of beta-adrenergic receptor blockade (46 +/- 8%), whereas the MVO2 response was less (28 +/- 3%). Again, the addition of cholinergic blockade to beta-blockade attenuated the increase in coronary vascular resistance (23 +/- 6%) without affecting the increase in MVO2 (25 +/- 4%). Combined alpha-, beta-, and cholinergic blockades abolished the systemic hemodynamic and coronary vasoconstrictor response to cocaine. CONCLUSIONS: In conscious dogs, cocaine induces coronary vasoconstriction, which competes with coronary vasodilator responses to increases in myocardial oxygen consumption. The mechanisms of cocaine's coronary vascular effects are mediated via adrenergic stimulation, and the intensity of the vasoconstrictor effects was reduced significantly by cholinergic blockade, in both the presence and absence of beta-adrenergic receptor blockade. PMID- 8443914 TI - Electrophysiological effects of high cocaine concentrations on intact canine heart. Evidence for modulation by both heart rate and autonomic nervous system. AB - BACKGROUND: Previous clinical reports have suggested that cocaine intoxication may produce severe ventricular arrhythmias due to a direct effect on the heart. However, the effects of high plasma levels of cocaine on the electrophysiology of the heart have not been well characterized and remain poorly understood. METHODS AND RESULTS: The purpose of this study was to characterize the electrophysiological effects of high doses of cocaine on the in situ dog heart. In dogs anesthetized with morphine and alpha-chloralose, cocaine (2-11 micrograms/mL) increased both atrial and ventricular refractory periods and produced rate-dependent increases in atrial, atrioventricular, His-Purkinje, and ventricular conduction intervals. The time constant for the onset of cocaine's conduction slowing effect following a reduction in pacing cycle length from 400 to 260 msec was approximately two beats, and the time constant for diastolic recovery from conduction slowing was approximately 200 msec, which are similar to values reported for several class Ib antiarrhythmic drugs. Cocaine produced a rate-dependent increase in QT interval that was greatest at high heart rates yet produced no change in the ST (QT-QRS) interval. This suggests that high plasma levels of cocaine delay repolarization primarily via slowing of conduction. Cocaine's effects on both atrioventricular and intraventricular conduction were significantly larger in autonomically blocked than in autonomically intact animals. CONCLUSIONS: We conclude that high plasma levels of cocaine, similar to those reported in autopsy reports following fatal cocaine overdose in humans, produce significant rate-dependent conduction slowing effects on atrial, atrioventricular, and ventricular conduction in the in situ heart. These rate dependent effects are intensified following autonomic blockade. PMID- 8443915 TI - Heat-shock response and limitation of tissue necrosis during occlusion/reperfusion in rabbit hearts. AB - BACKGROUND: Induction of stress proteins, such as heat-shock protein 71 (HSP71), is associated with cardioprotection in isolated ischemic myocardium. We tested this hypothesis in rabbits pretreated with whole-body hyperthermia and then subjected to 30 or 45 minutes of regional coronary occlusion (CO) followed by 3 hours reperfusion (Rep). METHODS AND RESULTS: Control rabbits did not undergo whole-body hyperthermia; heat-shocked (HS) rabbits were subjected to whole-body hyperthermia at 42 degrees C for 15 minutes. Rabbits were allowed to recover from whole-body hyperthermia for 24 or 40 hours and were then subjected to CO/Rep. Heart rate and arterial blood pressure were recorded during the experiments. Area of necrosis (tetrazolium staining) was normalized to anatomic risk zone size (microsphere autoradiography). In rabbits treated with whole-body hyperthermia and 24 hours of recovery, infarct size was significantly reduced in HS rabbits compared with control rabbits (41.2 +/- 7.8% versus 23.2 +/- 6.6%; p < or = 0.05; mean +/- SD) after 30 minutes of CO and 3 hours of Rep. Risk zone size was similar for the two experimental groups. In rabbits treated with whole-body hyperthermia and 40 hours of recovery, infarct size was similar for control and HS animals with either 30 or 45 minutes of CO (p = NS) and 3 hours of Rep. Risk zone size and area of necrosis were similar for these experimental groups. Biopsies from ischemic and nonischemic myocardium were obtained from rabbits at 24 and 40 hours after heat shock and control rabbits to verify expression of HSP71; expression was determined by Western blot analysis. CONCLUSIONS: Our findings demonstrate a considerable increase in expression of HSP71 in myocardium from hyperthermia-treated rabbits. Infarct size was significantly reduced after 30 minutes of CO and 3 hours of Rep in hearts at 24 but not 40 hours after heat shock compared with control hearts. We conclude that heat shock-induced cardioprotection is transient and delays the onset of irreversible myocardial injury caused by ischemia. PMID- 8443916 TI - Beneficial effect of carnitine on mechanical recovery of rat hearts reperfused after a transient period of global ischemia is accompanied by a stimulation of glucose oxidation. AB - BACKGROUND: We have previously shown that increasing myocardial carnitine levels in fatty acid-perfused isolated working rat hearts dramatically increases glucose oxidation rates. Since high levels of fatty acids depress reperfusion recovery of ischemic hearts by inhibiting glucose oxidation, we determined what effect carnitine has on glucose oxidation during reperfusion of ischemic hearts. METHODS AND RESULTS: Isolated working rat hearts were perfused with 11 mM [5-3H/ul 14C]glucose, 1.2 mM palmitate, and 100 microU/ml insulin and subjected to a 35 minute period of global ischemia followed by aerobic reperfusion. Rates of glycolysis and glucose oxidation were determined by measuring tritiated water and 14CO2 production, respectively. Before ischemia, myocardial carnitine content was first increased by perfusing hearts during a 60-minute baseline aerobic perfusion with 10 mM L-carnitine. This resulted in a significant increase in total myocardial carnitine from 4,804 +/- 358 to 9,692 +/- 2,090 nmol/g dry wt (mean +/ SD). Glycolysis rates in carnitine-treated hearts were not significantly altered compared with control hearts during the aerobic perfusion (2,482 +/- 1,173 versus 1,840 +/- 1,365 nmol glucose.g dry wt-1 x min-1, respectively). In contrast, glucose oxidation rates in carnitine-treated hearts were significantly increased before ischemia compared with control hearts (471 +/- 209 versus 158 +/- 75 nmol glucose.g dry wt-1 x min-1, respectively). During reperfusion of previously ischemic hearts, glycolytic rates returned to preischemic values in both carnitine-treated and control hearts. Glucose oxidation rates also recovered to preischemic values in these hearts and remained significantly elevated in carnitine-treated hearts compared with control hearts (283 +/- 113 versus 130 +/- 27 nmol glucose.g dry wt-1 x min-1, respectively). Mechanical recovery in control hearts returned to 44% of preischemic values (measured as heart rate-peak systolic pressure product), whereas in carnitine-treated hearts, mechanical recovery returned to 71% of preischemic values. CONCLUSIONS: These results suggest that the beneficial effects of carnitine in the ischemic heart can be explained by the actions of this compound on overcoming fatty acid inhibition of glucose oxidation. PMID- 8443917 TI - Superoxide dismutase restores contractile and metabolic dysfunction through augmentation of adenosine release in coronary microembolization. AB - BACKGROUND: This study was undertaken to test the hypothesis that administration of superoxide dismutase (SOD) restores the contractile and metabolic dysfunction in coronary microembolization and that these beneficial effects of SOD are attributable to the restoration of 5'-nucleotidase activity and subsequent augmentation of adenosine release. METHODS AND RESULTS: In 78 dogs before and after an injection of microspheres (15 microns in diameter) into the left anterior descending coronary artery, regional coronary blood flow (CBF), fractional shortening (FS), and lactate extraction ratio (LER) were measured with and without administration of recombinant human SOD (50 micrograms/kg/min i.c.). In the untreated dogs (n = 6), both FS and LER decreased after coronary microembolization (2.0 x 10(5) microspheres per ml CBF [mL/min]). FS and LER decreased from 24.2 +/- 1.3% to 5.1 +/- 1.2% and from 23.0 +/- 1.1% to -10.5 +/- 2.9%, respectively. These ischemic changes were associated with coronary hyperemic flow (141 +/- 8 versus 92 +/- 1 mL/100 g/min) and adenosine release (5.8 +/- 0.5 versus 0.4 +/- 0.1 nmol/100 g/min). Pretreatment with SOD augmented the hyperemic flow to 164 +/- 4 mL/100 g/min and enhanced the release of adenosine (9.6 +/- 0.6 nmol/100 g/min) associated with improvement of functional and metabolic dysfunction (FS, 14.8 +/- 2.3%; LER, 15.1 +/- 3.1%). Administration of SOD at 10 minutes (n = 5) and 30 minutes (n = 5) after coronary embolization restored the contractile function and lactate metabolism (at 10 minutes: FS, 16.7 +/- 2.2% and LER, 16.7 +/- 3.9%; at 30 minutes: FS, 11.1 +/- 1.3% and LER, 7.2 +/ 3.1%). However, administration of SOD 60 minutes after coronary embolization (n = 6) did not restore the contractile and metabolic dysfunction. The restoration of the contractile and metabolic dysfunction by SOD treatment was blunted by adenosine receptor blockade with 8-phenyltheophylline (n = 5). Myocardial 5' nucleotidase activity at 2 hours after embolization was restored with SOD treatment at 10 minutes (n = 5) and 30 minutes (n = 5) after embolization. However, SOD treatment at 60 minutes after embolization (n = 6) did not restore 5'-nucleotidase activity compared with the SOD pretreatment group. Furthermore, coronary submaximal vasodilation induced by papaverine (n = 5) and adenosine (n = 5) abolished the beneficial effects of SOD. CONCLUSIONS: We conclude that 1) in sustained myocardial ischemia, SOD treatment attenuates ischemic injury caused by coronary microembolization by restoration of 5'-nucleotidase activity and augmentation of adenosine release; 2) this beneficial effect of SOD is observed even after coronary microembolization; and 3) the beneficial effects of SOD are attributable to coronary vasodilation produced by augmented adenosine release. PMID- 8443918 TI - Comparative immunogenicity and thrombolytic properties toward arterial and venous thrombi of streptokinase and recombinant staphylokinase in baboons. AB - BACKGROUND: Streptokinase is a routinely used thrombolytic agent that is immunogenic and relatively inefficient toward platelet-rich thrombus, whereas staphylokinase is a poorly studied fibrinolytic agent. Here, the comparative immunogenicity and thrombolytic properties toward arterial platelet-rich thrombus and venous whole blood clots of streptokinase and recombinant staphylokinase were studied in baboons. METHODS AND RESULTS: The inhibitory capacity of baboon plasma (in a human plasma-based clot lysis assay) was 0.39 +/- 0.25 microgram streptokinase and 0.04 +/- 0.05 microgram recombinant staphylokinase per milliliter of plasma (mean +/- SD, n = 9). Intravenous infusion over 1 hour of 0.300 mg/kg of streptokinase at 0, 1, 2, 3, and 5 weeks in five baboons given heparin and the antiplatelet agent ridogrel increased the streptokinase neutralizing titer from 0.22 +/- 0.18 microgram/mL plasma at baseline to 3.8 +/- 4.4 micrograms/mL after 2 weeks (p = 0.043 versus baseline by Wilcoxon signed rank test) and to 4.4 +/- 4.6 micrograms/mL after 5 weeks, whereas the thrombolytic potency toward a 125I-fibrin-labeled plasma clot inserted into an extracorporeal arteriovenous loop was reduced from 84 +/- 7% at baseline to 45 +/ 8% after 2 weeks and to 36 +/- 8% after 5 weeks (p < 0.01 versus baseline). Administration over 1 hour of 0.065 mg/kg recombinant staphylokinase at 0, 1, 2, 3, and 5 weeks in four baboons did not induce measurable staphylokinase neutralizing activity in three of the four animals after 5 weeks. In the fourth baboon, a staphylokinase-neutralizing activity of 0.8 and 1.5 micrograms/mL was found at 3 and 5 weeks, respectively. Repeated staphylokinase administration was not associated with inhibition of clot lysis (43 +/- 4% lysis at baseline, 52 +/- 9% at 3 weeks, and 61 +/- 14% at 5 weeks; p = NS versus baseline). Repeated administration of streptokinase but not of staphylokinase caused a marked (> 50%) decrease in blood pressure, requiring administration of steroids and intravenous fluids, and a marked increase in leukocyte count and hemoglobin concentration. Intravenous infusion of streptokinase or recombinant staphylokinase over 1 hour in doses ranging between 0 and 1.0 mg/kg in three groups of four baboons each induced dose-dependent lysis of a 125I-fibrin-labeled autologous jugular vein blood clot (50% lysis requiring 0.140 mg/kg streptokinase and 0.058 mg/kg recombinant staphylokinase, representing equimolar amounts of 3.25 nmol/kg) without systemic fibrinogen depletion. The thrombolytic potency toward platelet rich arterial thrombus of streptokinase and recombinant staphylokinase were studied in a femoral arterial eversion graft model. Arterial recanalization with recombinant staphylokinase was more frequent and more persistent than with streptokinase (all p < 0.05). Intravenous infusion of 1.0 mg/kg streptokinase or 0.25 mg/kg recombinant staphylokinase in two groups of four baboons each given intravenous heparin (200-unit bolus and 50 units.kg-1 x hr-1) and aspirin (10 mg/kg) did not produce a significant prolongation of the median template bleeding time. CONCLUSIONS: Recombinant staphylokinase has a thrombolytic potency toward jugular vein blood clots in baboons comparable to that of streptokinase, but it is less immunogenic and less allergenic and it does not induce resistance to lysis upon repeated administration; it is significantly more efficient than streptokinase for the dissolution of platelet-rich arterial eversion graft thrombi. Recombinant staphylokinase, which can be easily obtained in active form by expression in Escherichia coli, may constitute a potentially useful alternative to streptokinase for the treatment of acute myocardial infarction. PMID- 8443919 TI - An evaluation of methods for imaging and quantifying coronary and carotid lumen stenosis and atherosclerosis. AB - BACKGROUND: Methods for imaging arterial disease manifest by compromise of the lumen or thickening of the walls are undergoing continuing development and refinement. Methods used for many years to image arterial lumens (e.g., angiography, Doppler ultrasound) are of greatest utility for assessing the relation of arterial disease to clinical outcome. Newer methods (B-mode ultrasound) visualize arterial walls and thus provide qualitatively different information that has not previously been available to investigators and that is particularly suitable for studies of the relation of risk factors to arterial disease. METHODS AND RESULTS: Methodology for imaging arterial lumens considerably antedates that for imaging walls, adequately describes severe stenosis, is relevant to the relation of arterial disease to clinical outcome, and is sufficiently reliable to support clinical trials. Angiographic morphology is increasingly recognized as an important contributor to disease outcome. However, despite developments in imaging (e.g., quantitative coronary angiography), validity is poor for identification of early disease or advanced disease of the wall of the artery that does not obstruct the lumen. B-mode ultrasound is a newer method for imaging arterial disease that provides reliable and valid estimates of early disease of arterial walls. Such minimally obstructive disease may be clinically relevant, and quantification of disease of the arterial wall permits the investigator to develop normative data for wall thickness and to explore precise dose-response relations between risk factors and extent of disease. Only invasive methods are available for imaging the coronary arteries, whereas both invasive and noninvasive methods are suitable for imaging extracranial carotid and ileofemoral arteries. Noninvasive (B-mode, Doppler) imaging of arteries affords the opportunity to carry out cross-sectional studies, cohort studies, and clinical trials with far less bias than studies relying on invasive imaging. CONCLUSIONS: Methods of imaging lumen stenosis complement those that image the arterial wall and provide different information. The development of new, safe, low-cost, noninvasive methods that can quantify early atherosclerosis of peripheral arteries has resulted in a broad range of opportunities for epidemiological studies. The choice of method should be governed by the experimental design and question to be answered. PMID- 8443920 TI - Coronary atherosclerosis. A multifactorial disease. AB - BACKGROUND: Several of the theories on the pathogenesis of atherosclerosis may be integrated into a single multifactorial one. According to this theory, the most likely sequence of events involved in early atherosclerosis is vascular dysfunction and/or injury, monocyte recruitment and macrophage formation, lipid deposition, vascular smooth muscle cell proliferation (mitogenic factor mediated), and synthesis of extracellular matrix. The interaction of all these factors will configurate the typical characteristic of the atherosclerotic plaque. METHODS AND RESULTS: Accumulating experimental and clinical data suggest two pathways in atherosclerotic progression. In some cases, the very slow process of the pathogenesis of early lesions may be significantly accelerated by means of thrombus formation and organization. Thrombosis is a key process in the pathogenesis of late atherogenesis and in the development of acute ischemic syndromes. CONCLUSIONS: The possibility of retarding human atherosclerosis or even inducing its regression is one of the present therapeutic challenges. Of the different approaches to this question, one approach aims at better control of risk factors, especially plasma lipid levels. Another approach attempts to enhance the removal of lipids from the arterial wall by increasing plasma high density lipoprotein levels. Each of these approaches, by acting on the lipid-rich plaques more prone to rupture, might prevent plaque progression and induce regression to prevent acute coronary events. A third approach, based on the key role of platelet thrombus formation in the conversion of chronic to acute events, would be the use of antithrombotic therapy. This last approach may partially prevent progression of the disease. PMID- 8443921 TI - AHA symposium/epidemiology meeting: Atherosclerosis. Discussion: Why measure atherosclerosis? PMID- 8443922 TI - Advantages and limitations of serial coronary arteriography for the assessment of progression and regression of coronary atherosclerosis. Implications for clinical trials. AB - BACKGROUND: Clinical trials with angiographic end points have been used to assess whether interventions influence the evolution of coronary atherosclerosis because sample size requirements are much smaller than for trials with hard clinical end points. Further studies of the variability of the computer-assisted quantitative measurement techniques used in such studies would be useful to establish better standardized criteria for defining significant change. METHODS AND RESULTS: In 21 patients who had two arteriograms 3-189 days apart, we assessed the reproducibility of repeat quantitative measurements of 54 target lesions under four conditions: 1) same film, same frame; 2) same film, different frame; 3) same view from films obtained within 1 month; and 4) same view from films 1-6 months apart. Quantitative measurements of 2,544 stenoses were also compared with an experienced radiologist's interpretation. The standard deviation of repeat measurements of minimum diameter from the same frame was very low (0.088 mm) but increased to 0.141 mm for measurements from different frames. It did not increase further for films within 1 month but increased to 0.197 mm for films 1-6 months apart. Diameter stenosis measurements were somewhat more variable. Measurement variability for minimum diameter was independent of vessel size and stenosis severity. Experienced radiologists did not systematically overestimate or underestimate lesion severity except for mild overestimation (mean 3.3%) for stenoses > or = 70%. However, the variability between visual and quantitative measurements was two to three times higher than the variability of paired quantitative measurements from the same frame. CONCLUSIONS: Changes of 0.4 mm or more for minimum diameter and 15% or more for stenosis diameter (e.g., 30-45%), measured quantitatively, are recommended as criteria to define progression and regression. Approaches to data analysis for coronary arteriographic trials are discussed. PMID- 8443923 TI - Invasive versus noninvasive studies of risk factors and atherosclerosis. AB - Associations of risk factors with atherosclerosis may be assessed by either invasive methods for measuring the arterial disease, such as angiography, or noninvasive methods; these methods differ in their potential for bias. Biases associated with coronary angiography may be difficult to control in statistical analysis, either because they are unrecognized or because they are amenable to neither stratification nor multivariate analysis. Problems in control selection include the likelihood that angiography controls overrepresent related ischemic or noncoronary cardiac conditions with their own risk factor associations. Differential misclassification is more likely in the clinical setting when invasive studies are used than in a research setting involving ultrasound imaging of carotid arteries. Nondifferential misclassification, however, affects both types of studies and clouds interpretation of the comparative strength of risk factor associations with atherosclerosis assessed by the two methods. Recent angiographic studies have generally provided insufficient information to evaluate these biases. However, with proper attention to such biases, one may be able to learn much about early and late stages of atherosclerosis by comparing risk factor associations with disease measured by both coronary angiography and carotid ultrasound. PMID- 8443924 TI - Which risk factors are associated with atherosclerosis? PMID- 8443925 TI - Ultrasound B-mode imaging in observational studies of atherosclerotic progression. AB - BACKGROUND: Investigations of the progression of atherosclerosis in human arteries suggest that changes in the thickness of the arterial intima-media complex, observable with B-mode ultrasonography, may precede development of atherosclerotic lesions. For epidemiological studies and clinical trials, B-mode ultrasound has the advantage that it is noninvasive, can be used in nonsymptomatic subjects, and can be carried out repeatedly, thus reducing the necessary sample size. In the Kuopio Ischaemic Heart Disease Risk Factor Study, we have assessed the reliability of B-mode ultrasound through studying intraobserver and interobserver variability. We have also investigated its predictive value by associating ultrasound observations with clinical end points, risk factors for common carotid and femoral atherosclerosis, and predictors of progression of common carotid atherosclerosis. METHODS AND RESULTS: The study of B-mode ultrasound reliability was conducted in 10 middle-aged men, with initial and two repeat scannings. The between-observer coefficient of variation was 10.5% for the first assessments by four observers. The intraobserver variability, described as the mean of the absolute difference between the first and third observations, was 0.087 mm, or 8.3% of the mean intimal-medial thickness (IMT). Ultrasonographic assessment of 1,257 men was compared with diagnostic information obtained from a prospective registry for acute myocardial infarction (AMI). The presence of any atherosclerotic findings was associated with a 3.0-fold risk of AMI. For each 0.1 mm of common carotid IMT, AMI risk increased by 11% (p < 0.001). Common carotid artery and femoral artery atherosclerosis, as assessed by mean maximal IMT, had different risk factor profiles. Age, serum low density lipoprotein cholesterol, smoking, platelet aggregability, serum copper, serum selenium (inversely), and blood hemoglobin were the strongest predictors of 2 year increase of common carotid IMT. CONCLUSIONS: On the basis of our experience and findings, the ultrasonographic assessment of common carotid atherosclerosis appears to be a feasible, reliable, valid, and cost-effective method for both population studies and clinical trials of atherosclerosis progression and regression. PMID- 8443926 TI - A maximum confidence approach for measuring progression and regression of coronary artery disease in clinical trials. AB - BACKGROUND: Imaging trials using arteriography have been shown to be effective alternatives to clinical end point studies of atherosclerotic vascular disease progression and the effect of therapy on it. However, lack of consensus on what end point measures constitute meaningful change presents a problem for quantitative coronary arteriographic (QCA) approaches. Furthermore, standardized approaches to QCA studies have yet to be established. To address these issues, two different arteriographic approaches were compared in a clinical trial, and the degree of concordance between disease change measured by these two approaches and clinical outcomes was assessed. METHODS AND RESULTS: In the Familial Atherosclerosis Treatment Study (FATS) of three different lipid-lowering strategies in 120 patients, disease progression/regression was assessed by two arteriographic approaches: QCA and a semiquantitative visual approach (SQ-VIS). Lesions classified with SQ-VIS as "not," "possibly," or "definitely" changed were measured by QCA to change by 10% stenosis in 0.3%, 11%, and 81% of cases, respectively. The "best" measured value for distinguishing definite from no change was identified as 9.3% stenosis by logistic regression analysis. The primary outcome analysis of the FATS trial, using a continuous variable estimate of percent stenosis change, gave almost the same favorable result whether by QCA or SQ-VIS. CONCLUSIONS: The excellent agreement between these two fundamentally different methods of disease change assessment and the concordance between disease change and clinical outcomes greatly strengthens confidence both in these measurement techniques and in the overall findings of the study. These observations have important implications for the design of clinical trials with arteriographic end points. PMID- 8443927 TI - Methodological issues facing studies of atherosclerotic change. AB - BACKGROUND: The association between coronary heart disease and lesions of the coronary arteries has led to investigations of different interventions on atherosclerotic change. Currently, B-mode ultrasound of the peripheral arterial vessels, rather than arteriography of the coronary arteries, provides the most accurate evaluation of atherosclerotic disease extent in the patient. METHODS AND RESULTS: When measuring the effect of risk factor modification on atherosclerotic change, it is important to select appropriate methods and end points for quantifying disease and evaluating subsequent change. Measurements must be valid, precise, and reliable and require appropriate a priori definitions of end points and their change. Consistent methodology within studies is crucial. Multiple measurements and data reduction methods can increase the efficiency of comparisons and merit careful consideration. Missing data arising from nonvisualization of sites complicate analyses. Identifying both covariates of atherosclerotic change and possible confounding interventions require monitoring biochemical, physiological, and/or clinical variables and making inferences from these. CONCLUSIONS: To strengthen the rationale for use of B-mode ultrasonography in assessing the natural history of atherosclerosis, four methodological issues must be addressed: evaluation of primary end points using composite and/or individual measurements of atherosclerotic assessment from the carotid arteries, evaluation of new methodology that may allow assessment of the anatomy of specific lesions and/or their potential for rupture, development of methods making complementary use of both angiographic measurements of lumen diameter and ultrasound assessment of the arterial wall, and concrete demonstration of a direct link between increasing intimal-medial thickness and subsequent clinical events. The use of a continuous variable (intimal-medial thickness) in ultrasound studies offers cost/benefit advantages; this methodology continues to evolve. PMID- 8443928 TI - Can we measure and predict atherosclerotic progression? PMID- 8443929 TI - Meeting the diagnostic challenge of Behcet's disease. PMID- 8443930 TI - Lower-extremity arterial disease: tips on diagnosis and therapy. PMID- 8443931 TI - Physiologic evaluation of coronary flow: the role of positron emission tomography. AB - As the complexity, cost, and risks of cardiac interventions direct attention to careful selection of patients, the ability of diagnostic imaging techniques to provide quantitative documentation of the hemodynamic severity of coronary artery disease will assume greater importance. Among the various techniques currently in use, positron emission tomography yields superior spatial resolution and attenuation correction and has high sensitivity and specificity. The correlation of positron emission tomography results with coronary stenosis severity and the possibility of making quantitative flow measurements using oxygen-15 water suggest that cardiac positron emission tomography may be the best noninvasive approach for diagnostic purposes. PMID- 8443932 TI - Current hypertension management: separating fact from fiction. AB - In medicine, as in other fields, myths or speculations may be repeated so often and so widely that they are perceived as fact. To some extent, this may have occurred with regard to the treatment of hypertension, especially concerning the use of diuretics and beta blockers and the significance of their metabolic effects. An analysis of the available data indicates that the use of diuretics and, to some extent, beta-adrenergic inhibitors will effectively lower blood pressure and reduce morbidity and mortality. Similar analyses strongly suggest that the metabolic changes induced by these agents may not be of major clinical importance. The widespread dissemination of theories and speculations designed to convince physicians to avoid their use may have been overdone. Scientific facts, not extrapolations of data, should be used to make treatment decisions. PMID- 8443933 TI - Mechanical lithotripsy of large common bile duct stones. AB - Endoscopic removal of biliary calculi is a safe and effective alternative to surgical exploration of the common bile duct. However, as stones increase in diameter, endoscopic retrieval becomes more difficult and hazardous. Mechanical lithotripsy is an endoscopic technique used to crush common bile duct stones that are too large to be removed by conventional methods. In the 3 years following the introduction of this technique at our institution, 145 patients underwent endoscopic retrograde cholangiopancreatography for symptomatic choledocholithiasis. Endoscopic mechanical lithotripsy improved the overall success rate of common bile duct clearance from 86.2% to 94.5%. No morbidity or mortality was associated with the procedure. Therefore, we recommend mechanical lithotripsy when bile duct stones cannot be removed with conventional techniques. PMID- 8443934 TI - Flurbiprofen in the prophylaxis of migraine. AB - Flurbiprofen, a nonsteroidal anti-inflammatory drug with effects on prostaglandin synthesis, platelet serotonin release, and beta-endorphin, was studied for efficacy in migraine prophylaxis. Twenty-three patients completed the 20-week, placebo-controlled, double-blind, crossover trial. Flurbiprofen, in a dose of 100 mg twice daily, and placebo were each given for 8 weeks, with a 2-week "washout" period between the treatment periods. Flurbiprofen significantly reduced migraine intensity (P < .05), total hours with migraine (P < .015), and the dosing frequency of relief medication (P < .015). Total hours with migraine decreased by 41%, and the use of relief medication decreased by 31%. The reduction in migraine frequency did not reach statistical significance (P < .10). Adverse effects were infrequent. Based on the overall improvement in migraine parameters, flurbiprofen can be recommended for use in migraine prophylaxis. PMID- 8443935 TI - Tretinoin emollient cream 0.01% for the treatment of photoaged skin. AB - Tretinoin emollient cream 0.01% was used to treat 40 patients with photoaged skin of the face and forearms in a 48-week, randomized, double-blind, placebo controlled study. On the face, a significant difference between treatment groups was found in the investigator's global evaluation (P < .001), and in fine wrinkling (P < .001) and coarse wrinkling (P = .02) at 24 weeks. Tretinoin treated forearms showed significantly greater improvement in roughness, mottled hyperpigmentation, fine wrinkling, and lentigines at 24 and 48 weeks. More consistent improvement was seen on the forearms than on the face. Adverse experiences on the face in both treatment groups included dryness, peeling, and acne. No significant difference in reported adverse experiences was found between forearms in both treatment groups. On forearms, dermatitis was the most common adverse event. Tretinoin 0.01% was generally well tolerated, and skin irritation was minimal. Tretinoin emollient cream 0.01% is a potentially safe, effective treatment for photodamaged skin. PMID- 8443936 TI - Myasthenia gravis therapy: immunoadsorbent may eliminate need for plasma products. AB - This in vitro study assessed the effectiveness of a new immunoadsorbent (Asahi IM TR 350) in removing anti-acetylcholine receptor antibody from plasma with minimal loss of albumin. Plasma procured from a myasthenia gravis patient undergoing routine plasma exchange was perfused through the immunoadsorbent and recirculated in vitro to simulate a clinical treatment. To assess the temperature dependency of sorption, perfusion was performed at various temperatures. Plasma solute concentrations were taken before and after perfusion to calculate solute rejection coefficients. The immunoadsorbent has a high sorption capacity for anti acetylcholine receptor antibody, while allowing a minimum loss of albumin. For patients with myasthenia gravis, this immunoadsorbent can provide an alternative to plasma exchange that does not require the use of plasma products. PMID- 8443937 TI - Multisystem autoimmune dysfunction with early onset of bullous emphysema. AB - We report a patient with alopecia universalis, autoimmune dysfunction, and rapidly progressing bullous emphysema. These disorders have neither been reported together previously nor classified within a syndrome. To explain early-onset bullous emphysema associated with autoimmune disturbance requires further study; we encourage reporting of similar patients. PMID- 8443938 TI - Primary mediastinal myelolipoma. AB - Myelolipomas are benign tumors composed of fat cells and mature bone marrow elements. They usually occur in the adrenal glands; fewer than 20 extra-adrenal myelolipomas have been reported. Myelolipomas may be found in abdominal, pelvic, or mediastinal sites. We report a patient with a right posterior mediastinal myelolipoma that was successfully resected. PMID- 8443939 TI - Multidisciplinary treatment of an unconsummated marriage with organic factors in both spouses. AB - Successful treatment of a case of unconsummated marriage involved the expertise of a urologist, gynecologist, and psychologist working together in an interdisciplinary clinic to treat sexual dysfunction. Total duration of treatment was 18 months, and components included surgical correction of congenital chordee, surgical excision of a hymenal remnant blocking the vaginal introitus, laser treatment of endometriosis, and sex therapy evaluation and follow-up totalling five sessions for both partners. At the end of treatment the couple was having pleasurable sexual intercourse. PMID- 8443940 TI - Dr. George W. Crile. The father of physiologic surgery. PMID- 8443941 TI - Forgoing life-supporting or death-prolonging therapy: a policy statement. AB - Avoiding death is not always the preeminent goal of health care, and decisions about the use of life-supporting treatment may either hasten or forestall death. What are the health care professional's responsibilities regarding the use of life-supporting therapy? This report offers general and specific guidelines for termination of life-supporting treatment. PMID- 8443942 TI - PET in the evaluation of coronary artery disease. PMID- 8443943 TI - Topical tretinoin no panacea for photodamaged skin. PMID- 8443944 TI - Skin lesions: when to suspect systemic causes. PMID- 8443945 TI - Lipid screening: is measuring cholesterol enough? PMID- 8443946 TI - Cardiopulmonary exercise testing in patients with chronic obstructive pulmonary disease. AB - Severe chronic obstructive pulmonary disease is characterized by limited exercise capacity as a result of changes in pulmonary mechanics, abnormal gas exchange, altered cardiac function, respiratory muscle dysfunction, nutritional factors, and dyspnea. Cardiopulmonary exercise testing is a safe, effective method for objectively studying exercise performance and may be carried out using simple walk tests or more complicated treadmill or cycle-ergometry testing. Indications in patients with chronic obstructive pulmonary disease include defining the etiology of dyspnea, evaluating work disability or impairment, and assessing the response to therapy or the need for supplemental oxygen. It is also indicated in preoperative evaluation and as part of a pulmonary rehabilitation program. PMID- 8443947 TI - Monoamine oxidase inhibitors and elective surgery. AB - Monoamine oxidase inhibitor use is considered a contraindication for elective surgery. We reviewed 32 patients on a regimen of isocarboxazid 10 mg daily who underwent elective surgery. Their anesthetic management, postanesthesia outcome, and pharmacology are described. PMID- 8443948 TI - Futile medical treatment and patient consent. AB - What are a physician's ethical responsibilities when a patient or surrogate demands futile life-saving treatment? Recent attempts to define medical futility have implications for physician responsibility and may create exceptions to acquiring patient consent. Wording is proposed for a "futility clause" for use in do-not-resuscitate policies. PMID- 8443949 TI - Bullectomies for bullous sarcoidosis. AB - A 36-year-old woman presented with respiratory insufficiency due to cystic sarcoidosis. She had been previously treated with multiple courses of prednisone without improvement. Enlarging blebs involving both lower lobes impaired the function of the relatively spared upper lobes. Bilateral lower lobectomies were performed in one step via median sternotomy without complications, with prompt subjective and objective improvement of her respiratory status. One-stage bilateral upper-lobe bullectomy for bullous emphysema has been previously reported, but to our knowledge this is the first performance of one-stage bilateral lower-lobe bullectomies for cystic sarcoidosis. The immediate benefits were evident; long-term results will depend on the course of the underlying disease. PMID- 8443950 TI - The Maze procedure: surgical therapy for refractory atrial fibrillation. AB - Although atrial fibrillation is well tolerated by most patients, in some patients the consequences may be severe. The Maze procedure is a new open-heart operation that creates a carefully designed maze of incisions in the atrial myocardium; this maze then acts as an electrical conduit to channel atrial impulses from the sinoatrial node to the atrioventricular node. The Maze procedure has been shown to restore sinus rhythm and atrial systole (thus reducing the risk of thromboembolism), improve hemodynamics, alleviate palpitations, and eliminate the need for antiarrhythmic and anticoagulant drugs. We describe our first patient to undergo this operation. PMID- 8443951 TI - Potential molecular therapy for acute renal failure. AB - Ischemic and toxic acute renal failure is reversible, due to the ability of renal tubule cells to regenerate and differentiate into a fully functional lining epithelium. Recent data support the thesis that recruitment or activation of macrophages to the area of injury results in local release of growth factors to promote regenerative repair. Because of intrinsic delay in the recruitment of inflammatory cells, the exogenous administration of growth promoters early in the repair phase of acute renal failure enhances renal tubule cell regeneration and accelerates renal functional recovery in animal models of acute renal failure. Molecular therapy for the acceleration of tissue repair in this disease process may be developed in the near future. PMID- 8443952 TI - Expression of epidermal growth factor, transforming growth factor alpha and their receptor in gastro-oesophageal diseases. AB - This article is a review of aspects of the expression of the regulatory peptides; epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), and their receptor (EGF-R) in the epithelium of the human oesophagus and stomach in health and disease. It has become clear that TGF-alpha has increased expression in metaplastic, dysplastic and neoplastic tissue of the oesophagus compared with normal mucosa. The degree of abnormal expression becomes more marked as dysplasia increases. TGF-alpha expression is also increased in gastric neoplasias. EGF has a different pattern of expression, being decreased in oesophagitis and increased in gastritis. Although EGF is present in Barrett's oesophagitis, the expression of EGF does not discriminate between dysplastic and neoplastic epithelium. EGF-R is normally expressed on all gastro-intestinal epithelia, but its expression is increased in Barrett's epithelium, as well as in adenocarcinomas of the oesophagus and the stomach. The two peptides bind to their receptors on the mucosal cell membranes, and the co-expression of peptide and receptor is positively associated with varying degrees of cellular proliferation. The density of receptor expression may modulate the proliferative stimulus, leading to either mitogenic (regulated) or oncogenic (unregulated) growth. PMID- 8443953 TI - The short bowel syndrome: what's new and old? AB - Conditions which resulted in colonic preservation such as strangulated hernia, intestinal volvulus, and mesenteric infarction were once the main reasons for a major intestinal resection leading to the short bowel syndrome. Now Crohn's disease is the most common underlying diagnosis; such patients often have a jejunostomy. A measurement of the residual jejunal length from the duodenojejunal flexure makes possible predictions of patient outcome. Patients with a jejunostomy and less than 100 cm jejunum usually need long-term parenteral support, whereas 50 cm or more of jejunum usually suffices for adequate oral nutrition if the colon is preserved. While patients with and without a colon have problems with nutrient absorption, those with a jejunostomy also have problems of water, sodium and magnesium losses. Stomal losses may exceed oral intake and all such patients ('secretors') need parenteral supplements. Fluid and sodium losses can be reduced by octreotide, omeprazole or H2 blockers but not sufficiently to avoid the need for intravenous supplements. Colonic preservation increases the incidence of calcium oxalate renal stones (20%). Patients with and without a colon have a high prevalence of gallstones (40%). Clinically important intestinal adaptation occurs in those with a colon but not in those with a jejunostomy. Many surgical techniques, including small bowel transplantation, have been suggested to improve absorption, but as the quality of life of most patients with a short bowel is good with current treatments, they are not at present recommended. PMID- 8443954 TI - Assessment profiles of disease severity in ulcerative colitis. AB - There is no general agreement as to which activity profile or activity is preferable for the clinical assessment of ulcerative colitis. Examples of qualitative and quantitative indices are given. Most of the latter include clinical data, macroscopic evaluation at endoscopy and histological grading of inflammation. It is proposed that the activity of the disease, reflected by the patient's symptoms, might be the determinant of the treatment, and the severity of the disease, defined by objective means, could be assessed in scientific evaluation. PMID- 8443955 TI - The renaissance of abdominal tuberculosis. AB - During the last decade, abdominal tuberculosis (TB) has experienced a renaissance. The number of cases diagnosed in Western European and North American countries has dramatically increased. The reasons for this are multiple and include the appearance of AIDS as a significant disorder and the increased morbidity of peoples across the world with the migration of many people from areas of high incidence of TB to the West. Recent epidemiological work is reviewed, and its relationship to these changes considered. The distribution of disease along the gastrointestinal tract and in the mesentery is discussed. The frequency of involvement at various sites and the clinical symptoms caused by the disease are reviewed. The need to diagnose abdominal TB in the 1990s is considered in detail in areas where the disease had previously been thought rare. PMID- 8443956 TI - State of the art in the diagnosis and management of acute cholecystitis. AB - The analysis of 664 cases operated upon for acute cholecystitis as well as a review of the literature indicate the dramatic increase in the age of patients presenting with this complication. Other obvious changes: increasing rate of diabetes mellitus and acalculous cholecystitis. The development of preoperative and operative sonography has contributed greatly to the safety of surgery for acute cholecystitis. The majority of patients classified as having low risks should, at the present state of our knowledge, undergo early and definitive surgery. This approach has shown to be the most beneficial from both the medical and economic standpoint. High risk patients as well as patients refusing surgery are optimally treated by sonar-guided percutaneous transhepatic cholecystostomy. Among the recent changes observed over the last 5 years, a marked decrease in septic complications as well as in the length of hospital stay was noted. Both changes improve the cost-benefit ratio of early surgery in this condition. PMID- 8443957 TI - The skin immune system and psoriasis. PMID- 8443958 TI - Augmented lymphocyte binding to cultured endothelium in psoriasis. AB - Lymphocyte binding to cultured human umbilical vein endothelial cells was evaluated using a modified centrifugation binding assay in 15 patients with psoriasis and compared with three patients with atopic dermatitis, 11 patients with rheumatoid arthritis and 28 normal controls. Patients with psoriasis demonstrated 61% augmented lymphocyte binding compared with normal controls (P < 0.0001), which was not explained by differences in age and sex or an effect of psoriatic sera. In serial studies of six patients, this difference was found to be reversible with treatment and clinical improvement. Lymphocytes from patients with atopic dermatitis demonstrated decreased binding to endothelium (P < 0.005), while those from patients with rheumatoid arthritis were not different from normal controls. This is the first skin disease described in which augmented lymphocyte binding to endothelium occurs, and may represent a mechanism by which lymphocytes are targeted to psoriatic skin. PMID- 8443959 TI - Early time course of recruitment of immune surveillance in human skin after chemical provocation. AB - As part of the defence function of skin it seems probable that mechanisms exist for the rapid recruitment of immune surveillance to 'inspect' any foreign substance that penetrates the skin. In the present study, evidence of such mechanisms was sought by following the time course of early changes in distribution of immune cells, expression of cell adhesion molecules and cytokines after epicutaneous challenge with provoking chemicals to which subjects were known to be either specifically 'sensitive' or 'non-sensitive'; anthralin, an irritant chemical, was used as control. Fifty-seven individuals were studied and there were at least five biopsy samples at each time point. Regardless of whether individuals were sensitive or not, or of the type of chemical, dermal microvascular endothelial cells showed increased expression of the adhesion molecules ELAM-1 and VCAM-1 within 2 h, and ICAM-1 within 8 h. The intensity of immunohistochemical staining increased progressively up to 24 h. More vessels stained for ICAM-1 than for VCAM-1 or ELAM-1, implying that not every vessel expressed all three cell adhesion molecules. Another early change, observed 2 h after irritant challenge, was a significant increase in numbers of CD1a+ dendritic cells in the superficial dermis from a median of 3/high power field (hpf) to 9.5/hpf (P < 0.03). This was not observed with 'weak' provoking substances, such as nickel, but did occur with the potent provoking agent dinitrochlorobenzene (DNCB). Thus, as little as 2 h after contact with provoking chemicals, the skin activates cellular mechanisms to increase T cell infiltration for the presumed purpose of immune surveillance. These mechanisms are not dependent upon specific immune sensitivity and reflect a capacity of skin cells to respond to chemical provocation. PMID- 8443960 TI - CD23/Fc epsilon R11 expression in contact sensitivity reactions: a comparison between aeroallergen patch test reactions in atopic dermatitis and the nickel patch test reaction in non-atopic individuals. AB - The immunopathology of patch test reactions to aeroallergens in patients with atopic dermatitis (AD) has been compared to that of contact sensitivity reactions to nickel in non-atopic individuals. Both reactions were found to exhibit equivalent erythema and induration on gross examination at 48 h. Four millimetre punch biopsies were obtained at 48 h frozen, and cryostat sections stained with a panel of MoAbs. The distribution of macrophages, dermal dendritic cells, Langerhans cells, T lymphocytes and the expression of CD23 antigen was recorded. Increased numbers of dermal dendritic cells, macrophages, T lymphocytes and Langerhans cells were found in the dermal infiltrates of both the nickel patch test reactions and the aeroallergen patch test reactions compared with their respective controls. There were no significant differences between atopic patch test reaction and nickel patch test reaction samples in the tissue distribution of these cell types. There was a significant increase in CD23 expression on Langerhans cells and dermal dendritic cells in the atopic patch test reactions, whereas an increase was only observed on dendritic cells in nickel patch test reactions. No significant difference in CD23 expression was observed in the control skin samples taken from patients with AD, nickel-sensitive patients and normal controls. This study supports the hypothesis that the aeroallergen patch test reaction in atopic dermatitis is a delayed hypersensitivity reaction, yet is distinct from the contact sensitivity reaction to nickel in terms of raised expression of CD23. PMID- 8443961 TI - Control of human thyroid autoantibody production in SCID mice. AB - In order to determine the phenotype of the cells required for thyroid autoantibody production, peripheral blood mononuclear cells (PBMC) from patients with autoimmune thyroid disease (AITD) were transferred to severe combined immunodeficient (SCID) mice. The production of human IgG, thyroglobulin (Tg) antibody and thyroid peroxidase (TPO) antibody in the SCID recipients was monitored for up to 4 months. PBMC from 10 of 13 AITD patients produced substantial IgG (> or = 100 micrograms/ml) and detectable Tg and TPO antibodies in recipient mice. PBMC pretreated to deplete or enrich T cells produced low or undetectable thyroid-specific antibody in SCID mice. Depletion of CD4+ T cells resulted in much lower or undetectable IgG, Tg and TPO antibodies compared with levels seen in recipients of control PBMC. By contrast, depletion of CD8+ T cells from the PBMC had no overall effect on autoantibody production, although with PBMC from some patients CD8+ depletion possibly enhanced both IgG and autoantibody production. In eight of 10 experiments, autoantibody levels reached maximal titres before total IgG levels peaked. It is considered that thyroid autoantibodies are produced from memory B cells activated in SCID mice and that this activation is T cell- and CD4+ T cell-dependent. PMID- 8443962 TI - Study of induction of activation of human peripheral blood mononuclear cells with a non-activating form of anti-CD3 MoAb in autoimmune thyroid disease (AITD). AB - Anti-CD3 (OKT3) MoAb is a mitogenic agent which activates lymphocytes. We have studied the effects of murine anti-human OKT3 MoAb (IgG1) alone or in combination with IL-2, human thyroglobulin (Tg) and thyroperoxidase (TPO) antigens on the proliferation of whole peripheral blood mononuclear cells (PBMC) (including monocytes) or subtypes (T, CD4+, CD8+, B) as measured by tritiated thymidine (3H TdR) incorporation. B cell differentiation was studied by measuring numbers of IgG-secreting cells and specific anti-TPO/anti-Tg-secreting cells by SPOT ELISA. PBMC or lymphocyte subtypes, obtained from 45 patients with Hashimoto's thyroiditis (HT), 40 Graves' disease (GD) and 51 normal controls were cultured in 96 microtitre plates for 6 days in the presence of OKT3 MoAb at final concentrations 25-250 ng/ml, IL-2 15 U/ml, Tg and TPO (1 micrograms/ml). Then cultures were pulsed with 0.2 microCi 3H-TdR/well and incorporation was measured after 18 h. IgG and anti-TPO/Tg-secreting cells were detected at 7 days. Higher proliferative responses from whole PBMC preparations in response to any of the combinations including OKT3 MoAb were observed in the HT preparations, while the basal values were the lowest. IL-2 alone increased these responses markedly, but equally in all groups. IL-2 in combination with OKT3 had an additive effect on proliferation, with higher responses in HT. Tg and TPO antigens did not change these responses. Most HT preparations responded with their maximum proliferation to the lowest concentration of OKT3 MoAb (25 ng/ml), whereas in GD and control preparations of PBMC these responses were shifted to higher concentrations (250 ng/ml); even with those, proliferation was not so enhanced in controls when compared with HT and GD preparations. In contrast, the proliferative responses of T cells alone and subpopulations of CD8+ suppressor/cytotoxic cells were decreased in HT preparations compared with controls. Monocytes were necessary for proliferation. In the subpopulation of B cells (> 95% pure) and CD4+ helper/inducer cells, differences did not reach significance. In spite of the effect on proliferation, OKT3 MoAb only mildly but significantly increased the numbers of IgG-secreting cells in HT and GD preparations and did not stimulate synthesis of specific antibodies. Our data suggest that the increased proliferative responses of whole PBMC to OKT3 MoAb in HT preparations might be due to insufficient activation of T suppressor/cytotoxic cells. PMID- 8443963 TI - Evidence for iC3 generation during cardiopulmonary bypass as the result of blood gas interaction. AB - Earlier we have shown that iC3 is generated at the blood-gas interface in vitro and that the generation of this molecule is independent of complement activation and the composition of the gas. In order to investigate whether iC3 is also generated during cardiopulmonary bypass where blood comes into contact with oxygen bubbles, two bubble oxygenators were incubated at 37 degrees C with human heparinized blood. A continuous increase in the level of iC3 was shown in the oxygen-perfused bubble oxygenator (up to 100 nmol/l after 180 min) in contrast to the unbubbled control. Similarly, in plasma drawn from patients undergoing cardiopulmonary bypass using either bubble or membrane oxygenators, the levels of iC3 were shown to increase continuously during the operation. Furthermore, this form of C3 was found to be susceptible to cleavage by factor I. The formation of iC3 at the blood-gas interface in vivo could be a mechanism by which gas bubbles induce clinical manifestations associated with complement activation, e.g. during cardiopulmonary bypass, adult respiratory distress syndrome and decompression sickness. PMID- 8443964 TI - Molecular analysis of C3 allotypes in patients with nephritic factor. AB - The autoantibody nephritic factor (NeF) leads to complement consumption in vivo and is associated with type II mesangiocapillary glomerulonephritis (MCGN II) and partial lipodystrophy (PLD). The third component of complement (C3) exists in two common allotypic forms, C3S and C3F, distinguished at the protein level by electrophoresis. An increased frequency of the rarer C3F allele has been reported in several autoimmune conditions, including one small series of patients with NeF. However, patients with NeF have low levels of circulating C3 so that allotyping at the protein level is difficult. The molecular basis of the S/F polymorphism has recently been established: a single base change at the DNA level encodes a single amino acid substitution at the protein level. A second polymorphism, closely linked to the first, is defined by the MoAb HAV 4-1, and is also due to a single base change. These polymorphisms can therefore be analysed at the DNA level. We have used the amplification refractory mutation system (ARMS), a modification of the polymerase chain reaction (PCR), to analyse these two C3 polymorphisms at the DNA level in 26 patients with NeF. The allele frequencies of C3S and C3F were 0.673 and 0.327 (predicted values 0.79 and 0.2, chi 2 = 4.813, P < 0.05), giving a relative risk of 2.1 for the development of NeF conferred by the presence of a C3F allele. The HAV 4-1 allele frequencies were (-) 0.71 and (+) 0.29, i.e. not significantly different than predicted from the linked C3S/F allele frequencies. This is the largest series of patients with NeF yet published, and our data confirm an association between C3F and NeF. Possible mechanisms for for this link are discussed. PMID- 8443965 TI - Serum markers of T cell activation in relapses of Wegener's granulomatosis. AB - Levels of soluble IL-2 receptor (sIL-2R), soluble CD4 (sCD4) and CD8 (sCD8) were measured by sandwich ELISA as markers for T cell activation in serial serum samples from 16 patients showing 18 histologically proven relapses of Wegener's granulomatosis (WG). Levels of sIL-2R increased from 1065 U/ml (median, range 373 2345 U/ml) 6 months before the relapse to 1684 U/ml (median, range 486-3404 U/ml) at the moment of relapse for the whole group (P = 0.10). The eight major relapses showed a profound rise in sIL-2R levels, from 1008 U/ml (median, range 686-1553 U/ml) 6 months before the relapse, to 1994 U/ml (median, range 1469-3404 U/ml) at the moment of relapse (P < 0.01). The levels of sIL-2R at the moment of relapse were significantly higher at the eight major relapses than at the time of the 10 minor relapses (P < 0.05). Minor relapses were not accompanied by a significant rise in sIL-2R levels. Titres of antineutrophil cytoplasmic antibodies (ANCA) rose by two or more titresteps or from negative to positive in 15/18 patients during the 6 months period before the relapse. In all seven cases with both a rise of the ANCA titre and an at least 25% increase in sIL-2R levels, the rise in ANCA preceded the rise in sIL-2R by at least 1 month. The level of sIL-2R at the moment of relapse correlated with the level of C-reactive protein (r = 0.488, P < 0.05) and with the disease activity score (r = 0.824, P < 0.002). There were no significant changes in levels of sCD4 or sCD8, although the levels of sCD4 tended to be higher at the time of major relapses. We conclude that major relapses of Wegener's granulomatosis are accompanied by systemic T cell activation. T cell activation, however, does not appear to precede the rise in ANCA titre. PMID- 8443966 TI - Gender-related influences on the development of chronic graft-versus-host disease induced experimental lupus nephritis. AB - Autoimmune diseases are far more common in women than in men. In the incidence of systemic lupus erythematosus (SLE), the female-to-male ratio is as high as 10:1. This suggests that sex hormones may play a fundamental role in determining the susceptibility to these diseases. In order to investigate the sex-related differences in the inducibility of chronic graft-versus-host disease-related experimental lupus nephritis, lymphocytes from female DBA/2 donor mice were administered to either male or female (C57BL10 x DBA/2)F1 recipients. An additional group of male recipients received lymphocytes from male DBA/2 donors. After four cell transfers, female recipients developed a significantly higher albuminuria than both male groups. Serum concentrations of autoantibodies against glomerular basement membrane (GBM), collagen IV, and laminin were significantly higher in females 2-4 weeks after induction. Levels of circulating autoantibodies against renal tubular epithelial antigens (RTE) and nuclear antigens were not different between the sexes. In transfer studies, the necessity of the presence of anti-GBM and anti-RTE autoantibodies for the development of glomerulonephritis was confirmed. These findings indicate that: (i) in this model of lupus nephritis, susceptibility to glomerulonephritis is strongly influenced by sex related genes; and (ii) among the variety of autoantibodies occurring in this model of SLE, both anti-GBM and anti-RTE autoantibodies play a key role in the pathogenesis of glomerulonephritis. PMID- 8443967 TI - Detection of glomerular-binding immune elements in murine lupus using a tissue based ELISA. AB - The glomerulonephritis in systemic lupus erythematosus (SLE) is presumably triggered by the binding of circulating immune elements (autoantibodies and immune complexes) to the glomerulus; however, the nature of these elements is unclear. In order to detect and characterize such elements, we developed an ELISA using whole intact glomeruli as the substrate. With this assay, glomerular binding activity (GBA) was detected in the serum of MRL lpr, NZB x W, and B x SB mice, but not in non-autoimmune BALB/c mice. Less activity was present in the serum of C3H lpr, C57Bl/6J lpr and AKR lpr animals which develop signs of autoimmunity but only modest renal disease. The GBA in MRL lpr mice contained IgG (subclasses 1, 2a and 2b), but not IgG3, IgM, IgA, or C3. GBA was not significantly decreased by preadsorption of MRL lpr serum by DNA-agarose (although anti-DNA antibodies were). Binding activity in serum, however, was diminished by DNAase treatment. Fractionation of MRL lpr serum over a molecular sizing column showed that GBA eluted in a broad peak. GBA bound to the glomerulus ex vivo in a tissue-specific fashion and was enriched in renal eluates relative to serum in vivo. In sum, the binding activity detected by this assay appeared to be a heterogeneous entity (possibly in part immune complexes containing DNA) which bound specifically to the glomerulus and which appeared to parallel the presence of renal disease. This novel assay system may help elucidate the pathogenesis of SLE nephritis and have utility as a disease marker. PMID- 8443968 TI - Role of tumour necrosis factor and reactive oxygen intermediates in lipopolysaccharide-induced pulmonary oedema and lethality. AB - The purpose of this study was to characterize the role of tumour necrosis factor (TNF) and neutrophils (PMN) in the pathogenesis of pulmonary oedema induced by endotoxin (lipopolysaccharide (LPS)). Intraperitoneal administration to BALB/c mice of 0.6-1 mg of LPS caused pulmonary oedema and lethality. This was associated with production of TNF in serum and bronchoalveolar lavage fluid and with accumulation of PMN in the lung. In this experimental model, we could block TNF production by different means: pretreatment 30 min before LPS with 4 mg/kg of i.p. chlorpromazine (CPZ), 3 mg/kg of i.p. dexamethasone (DEX), 1 g/kg p.o. of N acetylcysteine (NAC, an antioxidant precursor of glutathione), or an anti-TNF MoAb. CPZ, DEX and anti-TNF completely prevented LPS lethality but not pulmonary oedema or pulmonary PMN infiltration, indicating that: (i) lung oedema is not the main cause of death after LPS; and (ii) lung oedema induced by LPS is not mediated by TNF. Pretreatment with NAC not only inhibited TNF production but also protected against LPS-induced pulmonary oedema, indicating that reactive oxygen intermediates are implicated. NAC also blocked TNF production in blood and in bronchoalveolar lavage. We also tested the effect of PMN depletion induced with cyclophosphamide (CP) or 5-fluorouracil (5-FU). While no pulmonary PMN infiltrate was observed in PMN-depleted mice, neutropenia did not prevent LPS lethality or oedema, indicating PMN do not play an important role in the toxic effects of LPS in this experimental model. PMID- 8443969 TI - Soluble plasma IL-2 receptors and malaria. AB - Plasma levels of soluble IL-2 receptor (sIL-2R) were measured by immunoassay in 180 individuals, aged 1-70 years, living in a malaria-endemic community in West Africa. sIL-2R levels were compared with age, malaria parasitaemia, malaria associated morbidity and cellular immune responses to Plasmodium falciparum antigens. Plasma levels of sIL-2R were independently associated with both age and patent malaria parasitaemia. No significant association was observed between IL 2R levels and concurrent malaria morbidity (i.e. fever associated with malaria), but the number of individuals with clinical malaria at the time of sampling was small. Although there was no association between plasma sIL-2R levels and in vitro proliferative responses of peripheral blood mononuclear cells (PBMC) to a number of defined malaria antigens, we did find a significant negative association between sIL-2R and in vitro proliferation of unstimulated PBMC. High levels of sIL-2R (up to 5500 U/ml) were detected in the plasma of malaria infected individuals; this is indicative of a vigorous cellular immune response to malaria antigens in vivo and does not support the notion that malaria infections are generally immunosuppressive. Indeed, we found that, at the low levels of parasitaemia present in study subjects, there was no significant difference in the mean proliferative response to malaria antigens in infected subjects when compared with uninfected subjects. PMID- 8443970 TI - Determination of the cytokine profile in American cutaneous leishmaniasis using the polymerase chain reaction. AB - The lymphokine profiles were determined in the skin lesions of the three distinct clinical forms of American cutaneous leishmaniasis (ACL), using a reverse transcriptase polymerase chain reaction (RT-PCR) and primers for various lymphokines. The message for interferon-gamma (IFN-gamma), tumour necrosis factor beta (TNF-beta), and IL-8 was expressed in the three clinical forms of ACL. IL-1 beta mRNA was expressed in most localized (LCL) and mucocutaneous (MCL) leishmaniasis, but in only few of the diffuse cutaneous leishmaniasis (DCL). IL-2 mRNA was detected in about half of the lesions, with more prominent values for MCL. IL-4 mRNA was present in most lesions from the three clinical forms, but markedly increased in DCL. IL-5 and IL-10 mRNAs were expressed in all MCL and in half of the DCL lesions and weakly expressed in LCL lesions. IL-10 mRNA was more abundant in MCL lesions. In contrast, IL-6 and TNF-alpha mRNAs were expressed in a large number of LCL. In MCL, IL-6 mRNA was expressed in most cases and TNF alpha mRNA in all the cases. In DCL, IL-6 mRNA was absent and TNF-alpha mRNA was weakly expressed. These results suggest that most T cells present in the MCL and DCL lesions secrete a mixture of type 1 and type 2 cytokine patterns, but in DCL granulomas type 2 cytokines predominate. In LCL the cytokine patterns show a mixture of type 1 and type 0 with a preponderance of IFN-gamma over IL-4, and low levels of IL-5 and IL-10. The lack of IL-6 and TNF-alpha mRNAs, and the low expression of IL-1 beta in DCL lesions suggest a defect in the antigen-processing cells that may account for the state of unresponsiveness in these patients. PMID- 8443971 TI - Modulation of human mesangial cell behaviour by extracellular matrix components- the possible role of interstitial type III collagen. AB - We have investigated the effects of various extracellular matrix (ECM) components on the behaviour of human mesangial cells (HMC) in a gel culture system using a modified MTT assay method. When cultured on a reconstituted basement membrane, Matrigel (M gel), HMC aggregated and formed isolated colonies initially, then extended an array of cell processes to form a dendritic network structure and proliferated very slowly as the culture period progressed. On type I collagen gel (CI gel), however, HMC developed elongated bipolar shapes, migrated into the gel, and showed rapid cell growth. Next, separate ECM components, such as type III and IV collagens, laminin, heparin and heparan sulphate, were incorporated into CI gel and HMC proliferation was assessed. Although attachment of HMC to each gel did not differ significantly, HMC proliferation was inhibited markedly on gels containing type III collagen, heparin and heparan sulphate; type IV collagen suppressed HMC proliferation slightly; and laminin had no significant effect. These data suggest that interstitial type I and III collagens, which are often observed in diseased glomeruli, as well as the basement membrane components, may play important roles in the regulation of HMC proliferation under pathophysiological conditions in vivo. We conclude that HMC behaviour is affected by the surrounding ECM constituents, which appear to function as a refined modulator. PMID- 8443972 TI - Renal fibroblasts are sensitive to growth-repressing and matrix-reducing factors from activated lymphocytes. AB - Various forms of nephropathy accompany interstitial fibrosis with lymphocytic infiltration. To probe the relationship between lymphocyte-derived factors and renal fibroblasts, we studied the effect of culture supernatant from lymphocytes stimulated by concanavalin A (ConASN) on the growth and matrix metabolism of rat kidney fibroblasts. 3H-thymidine incorporation and Northern analysis, respectively, revealed that ConASN repressed cell growth and the mRNA level of collagen type I, but dramatically elevated the steady-state expression of metalloproteinase transin/stromelysin. The growth inhibitor in ConASN was moderately heat-sensitive and less than 5 kD in molecular size, qualities that differed from those of transforming growth factor-beta (TGF-beta), IL-1 beta, IL 6, and tumour necrosis factor-alpha (TNF-alpha). The matrix regulatory factor in ConASN was highly heat-sensitive and more than 30 kD in size. Among several lymphokines tested, TNF-alpha produced the same effects as ConASN on the metabolism of extracellular matrix. We hypothesize that lymphocyte-derived factors have a significant role in the attenuation of renal fibrogenesis, as well as its progression, via inhibiting cell growth and matrix accumulation. PMID- 8443973 TI - Effects of AE0047 on renal haemodynamics and function in anaesthetized dogs. AB - 1. The effects of AE0047, a newly developed calcium channel blocker, on renal haemodynamics and function were investigated and compared with those of nicardipine in anaesthetized dogs. 2. Intravenous injection of AE0047 (10 and 30 micrograms/kg) caused a dose-related fall in blood pressure (BP). The AE0047 induced fall in BP was of slow onset and long lasting. AE0047 at 10 micrograms/kg elicited a slight increase in renal blood flow (RBF) and urine formation. 3. When AE0047 was infused intrarenally at non-hypotensive doses (25 and 50 ng/kg per min), there was no significant increase in RBF. However, the glomerular filtration rate increased significantly after drug infusion. Intrarenal arterial (i.r.a.) infusion of AE0047 led to dose-related increases in urine flow (UF), urinary excretion of electrolytes (Na+, K+ and Cl-) and fractional excretion of electrolytes. The AE0047-induced increase in urine formation was of very slow onset and progressed even after the cessation of the AE0047 infusion. 4. The intrarenal arterial infusion of nicardipine at same doses as AE0047 produced significant increases in urine formation, but these effects were immediately restored to the control values after cessation of the nicardipine infusion. 5. It was shown that AE0047 has a long-lasting diuretic effect and that AE0047-induced diuresis may be due to inhibitory effects on sodium and water reabsorption in the renal tubules. PMID- 8443974 TI - Acute effect of physiological concentrations of vasopressin on rat renal function. AB - 1. The antidiuretic, pressor and electrolyte transport effects of arginine vasopressin (AVP) were simultaneously evaluated in the anaesthetized water diuretic rat. Increasing concentrations of AVP (7.5, 75 and 750 ng/kg bolus and per h), were used to produce plasma levels which approximate the physiological range (408 +/- 2.4, 35.7 +/- 12.5, 85.2 +/- 16.1 pg/mL respectively). 2. Administration of a minimally effective antidiuretic dose (7.5 ng) increased mean urine osmolality (from 101 +/- 7 to 312 +/- 89 mosmol/kg) without altering mean arterial pressure (MAP), renal plasma flow (RPF) or glomerular filtration rate (GFR). A maximal antidiuretic dose of AVP (75 ng) increased mean urine osmolality to 2002 +/- 109 mosmol/kg and was associated with significant mean increases in MAP (9 mmHg), RPF and GFR (25%) by 30-60 min. A further ten-fold increase in AVP (750 ng) produced a greater increase in MAP (116 +/- 6 to 134 +/- 7 mmHg; P < 0.01) as well as increasing RPF and GFR by 35.5 and 38.9% respectively. 3. Increasing concentrations of AVP also progressively increased the fractional excretion of sodium, potassium and phosphate. However, fractional calcium and magnesium excretion was significantly decreased with maximal and supramaximal concentrations. 4. These studies support evidence that AVP is a pressor hormone in physiological concentrations in baroreceptor intact animals. Its role in renal electrolyte transport is unclear. Measured increases in RPF and GFR with the maximal and supramaximal AVP concentrations appear to be correlated with the increase in MAP. PMID- 8443975 TI - Effects of cortisol on blood pressure and salt preference in normal humans. AB - 1. Adrenocorticotrophic hormone (ACTH) and corticosteroids stimulate salt appetite in laboratory animals. The hypothesis tested was that cortisol administration increases salt preference in humans. 2. Sodium taste studies (detection and recognition thresholds, taste intensity and preference tests) were conducted before, during and after cortisol administration (200 mg/day for 5 days) in normal men on a free diet. 3. Cortisol significantly increased systolic blood pressure (SBP), 113 +/- 3 - 130 +/- 4 mmHg, P < 0.05; diastolic blood pressure (DBP), 65 +/- 3 - 81 +/- 2 mmHg, P < 0.05; mean arterial pressure (MAP), 81 +/- 2 - 97 +/- 3 mmHg, P < 0.05; and bodyweight, 72.9 +/- 3.0 - 75.4 +/- 3.3 kg, P < 0.05. 4. Salt detection and recognition thresholds, taste intensity and preference for sodium chloride were unchanged following cortisol. PMID- 8443976 TI - Cerebrovascular protection by sequential bilateral carotid artery ligation in aged spontaneously hypertensive rats. AB - 1. Sequential bilateral carotid artery ligation (BCL) separated by a 1 week interval was performed on 5 month spontaneously hypertensive rats (SHR) (i.e. SHRSR-B1/Izm) and the developmental course of hypertension and cerebrovascular lesions in advanced age were analysed as compared with those in age-matched sham operated controls. 2. Behavioural activity and behavioural reaction to light were also investigated in the above-mentioned SHR, young and adult stroke-prone SHR (i.e. SHRSP-A3/Izm), SHR (i.e. B1/Izm) and Wistar-Kyoto rats (i.e. WKY/Izm). 3. All of the control SHR developed severe hypertension resulting in cerebral stroke with focal oedema due to cerebral haemorrhage and infarction as a result of arterionecrosis 18 months after birth. 4. SHR usually die within a few days of BCL. In the present study, however, they successfully survived without cerebrovascular damage for a long time, although they developed a similar severe hypertension in a significantly shorter period of time (P < 0.05) and showed behavioural abnormalities that were probably due to severe cerebral ischaemia. 5. These experimental results suggest an ischaemic tolerance phenomenon in a hypertensive model that was exposed to mild ischaemic stress by unilateral carotid artery ligation (UCL) before the subsequent induction of severe ischaemia by BCL. The results also suggest that an aggravation of hypertensive cerebrovascular changes due to long-lasting ischaemia after BCL was prevented through a possible cumulative effect of ischaemic stress. PMID- 8443977 TI - Diabetic rat aorta responsiveness to D600 and nifedipine. AB - 1. The responsiveness of aortic rings from 4 and 12 week streptozotocin-induced diabetic rats to D600 (Gallopamil) and nifedipine was studied. 2. The sensitivity and responsiveness to D600 were significantly enhanced (P < 0.05; 5-test, ANOVA; 9 d.f.) only in the 4 week diabetic preparations precontracted with noradrenaline. 3. Nifedipine-induced relaxations were significantly enhanced (P < 0.05-0.01; t-test, ANOVA; 8-12 d.f.) in all the diabetic (4 and 12 weeks) aortic preparations precontracted with both noradrenaline (10(-7) mol/L) and KCl (40 mmol/L) when compared with controls. 4. D600, unlike nifedipine, did not produce significant relaxation of diabetic aortic preparations precontracted with KCl (40 mmol/L) at both week 4 and 12 of the disease when compared with controls. 5. These results suggest that there is differential responsiveness of streptozotocin diabetic rat aorta to D600 and nifedipine. PMID- 8443978 TI - Circulating levels of active, total and inactive renin (prorenin), angiotensin I and angiotensinogen in carbon tetrachloride-treated rats. AB - 1. Plasma renin activity (PRA), plasma angiotensin I concentration (ANG I), plasma angiotensinogen concentration (PAC) and the plasma levels of active, total and inactive renin (prorenin) were measured in rats with carbon tetrachloride (CCl4)-induced acute renal failure. Rats were treated with a single oral dose of CCl4 (2.5 mL/kg) and killed 1, 2, 3 and 7 days later. 2. On days 1-3 PRA, ANG I and PAC decreased and increased on day 7. Active renin fell on days 2 and 3, total renin (trypsin treatment) augmented on day 1 and diminished on day 3, prorenin and per cent prorenin increased on days 1 and 2. Angiotensin I concentration paralleled PRA and PAC. The CCl4-induced decrease in PRA was secondary to the fall in active renin and in PAC. Total renin augmented as a consequence of the elevation of prorenin. Renal function, evaluated by serum urea, serum creatinine and creatinine clearance, decreased on days 1 and 2 when PRA was low and plasma prorenin was high. 3. These data do not support the involvement of the circulating active renin-angiotensin system (RAS) in the pathophysiology of acute renal failure induced by CCl4, however, increased prorenin levels were associated with the decrease in renal function. PMID- 8443979 TI - Effects of adenosine and its analogues on actin polymerization in human polymorphonuclear leucocytes. AB - 1. The effects of adenosine and its analogues on actin polymerization in human polymorphonuclear leucocytes (PMN) induced by three different chemotactic stimulants, platelet-activating factor (PAF), N-formyl-methionyl-leucyl phenylalanine (FMLP) and an activated fragment of C5 (C5a) were investigated. 2. Adenosine and its analogues inhibited the actin polymerization induced by these three agents in a concentration-dependent manner and theophylline, a competitive antagonist at adenosine receptors, abolished these inhibitory effects. 3. The adenosine analogue 5'-N-ethylcarboxamideadenosine (NECA) was a more potent inhibitor of actin polymerization than either L-N6-phenylisopropyladenosine (PIA) or adenosine itself; the rank order of potency of these agonists was characteristic of adenosine A2 receptors. 4. Adenosine deaminase (ADA) abolished the inhibitory effect of adenosine and augmented PAF-induced actin polymerization. 5. It was concluded that, at physiological concentrations, adenosine inhibits actin polymerization in PMN via activation of PMN surface membrane adenosine A2 receptors and thus modulates chemotactic stimulus-induced PMN motility. PMID- 8443980 TI - Induction and regulation of IgA responses in the microenvironment of the gut. PMID- 8443981 TI - V delta 2+ gamma delta T lymphocytes are cytotoxic to the MCF 7 breast carcinoma cell line and can be detected among the T cells that infiltrate breast tumors. AB - In order to study the potential role of gamma delta T lymphocytes in cytotoxicity against breast carcinoma cells, normal peripheral blood gamma delta cells were isolated and triggered with an alloantigenic lymphoblastoid B cell line and recombinant interleukin-2 and cloned. The clones expressed a CD3+V gamma 9+V delta 2+CD4-CD8- (or CD8+) phenotype. Five clones were cytotoxic to the Molt 4 T cell leukemia, but not to the alloantigen, whereas one clone lysed the alloantigen, but not the Molt 4 line. Clones that were cytotoxic to Molt 4 were either spontaneously cytotoxic against MCF 7 breast carcinoma cells or could be induced to kill MCF 7 cells by monoclonal antibodies specific for the gamma delta T cell receptor. In situ staining demonstrated that V delta 2+ as well as other subsets of gamma delta T cells can be detected in the lymphocytic infiltrate within breast carcinomas. These data showing that V delta 2+ T cells can recognize and kill cells of breast carcinoma lineage in vitro, and that cells expressing V delta 2 genes in their T cell receptor structure can be detected in the tumor, suggest that further studies of the nature of the interactions between V delta 2 T cells and breast carcinoma cells are warranted. PMID- 8443982 TI - Chagas' disease: IgG isotypes against Trypanosoma cruzi cytosol acidic antigens in patients with different degrees of heart damage. AB - We studied the reactivity of IgG isotypes detected in sera from chronic Chagas' disease patients with a Trypanosoma cruzi cytosol acidic antigenic fraction (F IV) and parasite epimastigote forms (EPI). All patients studied had positive serology for Chagas' disease, with normal electrocardiogram (Group I), abnormal ECG without cardiomegaly (Group II), and abnormal ECG with cardiomegaly (Group III). The highest levels of antibodies were observed in sera from Group II patients. A high prevalence of IgG1 and IgG3, low levels of IgG2, and IgG4 isotypes against EPI were found in sera from all groups by ELISA. When the F IV was used as antigen, IgG1 was the main antibody isotype detected by ELISA in all groups of patients. The antigenic recognition patterns by IgG1 among the different clinical groups by immunoblotting of F IV revealed some differences. The sera from Group I recognized antigens of F IV of 80, 53, and 43 kDa. Sera from Group III recognized mainly one antigenic band of 43 kDa. Finally, sera from Group II showed greater diversity of binding by IgG1, detecting between one and six bands in the 80 and 30 kDa ranges. PMID- 8443983 TI - Cell surface expression of lysosome-associated membrane proteins (LAMPs) in scleroderma: relationship of lamp2 to disease duration, anti-Sc170 antibodies, serum interleukin-8, and soluble interleukin-2 receptor levels. AB - Lysosome-associated membrane proteins (LAMPs) are integral transmembrane proteins densely expressed on lysosomes which can be shuttled to the plasma membrane during cell activation. The objective of this study was to examine the expression of LAMPs on the cell surface of peripheral blood mononuclear cells (PBMCs) derived from patients with scleroderma. Heparinized blood was obtained from 23 patients with scleroderma and 15 healthy controls and PBMCs were isolated via a Ficoll gradient. Cells were stained with monoclonal antibodies directed against two of the major LAMPs, lamp1 and lamp2, and after subsequent staining with a fluorescent second antibody, were analyzed by flow cytometry. Two -and three color immunofluorescence was utilized to define the phenotype of LAMP+ cells. The proportion of PBMCs expressing lamp2 on the cell surface was significantly elevated in patients with scleroderma (2.21 +/- 0.38%) compared to controls (1.14 +/- 0.27%; P < 0.05). Multivariate analysis of patient subgroups indicated that the significant factors contributing to higher levels in patients were shorter duration of disease (P < 0.01) and greater functional disability related to disease manifestations (P < 0.01). Patients with anti-Scl70 antibodies had the highest levels of cell surface lamp2 expression (4.19 +/- 0.90%; P < 0.0005). The degree of cell surface lamp2 expression correlated with the level of sIL2R in 19 scleroderma patients (r = 0.48; P < 0.05). Serum IL4 and IL6 did not correlate with cell surface LAMPs or sIL2R. Five of 19 patients had detectable serum levels of interleukin-8 (IL8). These patients had significantly higher cell surface lamp2 expression than those with no detectable IL8 (3.76 +/- 0.48% vs 1.44 +/- 0.39%; P < 0.01). Extended phenotyping revealed that > 85% of lamp2+ cells expressed the B-cell antigen CD19. Cell surface lamp2 expression correlates with clinical and laboratory parameters in scleroderma patients and may reflect immune system activation. Additionally, this is the first report describing an elevation of serum IL8 in an autoimmune or collagen-vascular disease. PMID- 8443984 TI - Rheumatoid factor expression and complement activation in children congenitally infected with human immunodeficiency virus. AB - Rheumatic disease manifestations and autoimmune phenomena are common in adults infected with human immunodeficiency virus (HIV). On the other hand, rheumatic disease manifestations are rare in children congenitally infected with HIV. We studied the relationship between autoimmune phenomena and rheumatic diseases by examining HIV-infected children for the presence of rheumatoid factors (RFs), immune complexes, and complement activation fragments. RFs (principally IgA) were detected in 12 of the 24 HIV-infected patients (50%) and in none of the uninfected (HIV-exposed, seroreverted) controls (n = 22). Mean levels of complement activation fragments C3a and Bb were elevated in the HIV-infected children compared with the controls. A correlation was seen between the presence of IgA RF and alternative complement pathway activation as measured by plasma levels of Bb. None of the children had clinical or laboratory evidence of rheumatic disease. PMID- 8443985 TI - Histologic characterization of the thymus in canine X-linked severe combined immunodeficiency. AB - This study describes the thymic morphology in 52 dogs (ranging in age from 1 to 79 days) with X-linked severe combined immunodeficiency disease (XSCID). The thymuses from the XSCID dogs and age-matched controls were evaluated histologically for the presence of Hassall's corpuscles and branchial duct remnants, the degree of corticomedullary differentiation, and lymphoid development and organization. Within this population of XSCID dogs with the same genetic defect, three histologic patterns of thymic dysplasia were recognized. Simple dysplasia, noted in 27 XSCID thymuses, was characterized by varying numbers of lymphocytes, no corticomedullary demarcation, and an absence of Hassall's corpuscles. Dysplasia with Hassall's corpuscles was noted in 21 dogs and consisted of varying numbers of lymphocytes, no corticomedullary demarcation, and varying numbers of Hassall's corpuscles. Dysplasia with partial corticomedullary demarcation, noted in 4 dogs, consisted of relatively normal looking thymuses with well-defined corticomedullary demarcation and numerous Hassall's corpuscles; however, the lobules were extremely small and the subcapsular cortical region was devoid of lymphocytes. Cystic branchial duct remnants were present in 46 of the 52 XSCID thymuses and were more numerous in those thymuses with the pattern of simple dysplasia. The thymuses of XSCID pups less than 4 weeks of age were of the simple dysplastic type and thymuses of XSCID dogs greater than 4 weeks of age were more developed, as evidenced by increased numbers of Hassall's corpuscles and greater corticomedullary demarcation. In conclusion, the thymic dysplasia and lymphoid hypoplasia associated with X-linked severe combined immunodeficiency disease in the dog does not appear to be due to a developmental arrest but rather due to an active process dependent on factors probably related to the overall genetic defect. PMID- 8443986 TI - Quantitative measurement of human thyroglobulin-specific antibodies by use of a sensitive enzyme-linked immunoassay. AB - A quantitative enzyme-linked immunoassay that measures in absolute terms the subclass concentration of human thyroglobulin (huTg)-specific IgG autoantibody was developed. Unique to this study was the use of an affinity-purified anti-huTg standard with a known concentration of the four IgG subclasses. The sensitivity of the ELISA assay was 1-5 ng/ml depending on the IgG subclass being measured. We examined 22 sera of patients with autoimmune thyroid disease. The total huTg specific antibody concentrations in serum ranged from 0 to nearly 3000 micrograms/ml of IgG. The IgG subclass distribution in individuals with low huTg specific IgG (< 10 micrograms/ml) was primarily IgG1 and IgG3 Ab. Patients with intermediate levels of huTg IgG (10-600 micrograms/ml) expressed all four subclasses; however, no particular subclass was dominant. Individuals with > 1000 micrograms/ml also showed huTg-Ab in all four subclasses, however, IgG1 and IgG2 were dominant. All four IgG subclasses were used in the response to huTg, although the pattern of usage varied between individuals. There was no dominant subclass usage seen in this patient population. PMID- 8443988 TI - The center for human caring. PMID- 8443987 TI - Treatment of experimental autoimmune dacryoadenitis with cyclosporin A. AB - Experimental autoimmune dacryoadenitis (EAD) was induced in SJL/J mice by a single injection of purified lacrimal gland antigen (LG-Ag) in complete Freund's adjuvant. The disease is characterized by lymphocytic infiltration of the lacrimal gland and production of lacrimal gland-specific antibodies. We examined the effects of cyclosporin A (CsA) on the development and progression of this inflammatory disease. CsA (100 mg/kg/day), given from the time of immunization for 14 days, completely blocked the development of EAD in all treated mice. Both cellular and humoral immune responses to LG-Ag were markedly reduced by the administration of CsA as evidenced by the near absence of lymphocyte proliferative response and the reduced production of circulating anti-LG-Ag antibodies. Delayed CsA treatment beginning on Day 7 after immunization totally abrogated the development of lacrimal histological lesions and lymphocyte proliferative response to LG-Ag. However, serum anti-LG-Ag titers were only marginally decreased in CsA-treated animals. Treatment with CsA was found effective even when daily injections were started 14 days after immunization with LG-Ag. CsA prevented the inflammatory cell response in 5 of 10 mice when the disease was established. The lymphocyte proliferative response to LG-Ag was moderately depressed in CsA-treated animals, but antibody titers were the same as those in the oil-treated control. These studies demonstrate that CsA has a therapeutic effect in this murine model of dacryoadenitis and suggest a critical role for T lymphocytes in the pathogenesis of EAD. PMID- 8443989 TI - The puzzle of normal coronary arteries in the patient with chest pain: what to do? AB - Over one million Americans undergo cardiac catheterization each year because of chest pain, with the expectation that coronary artery disease will be found. However, up to 30%--a subgroup that includes patients with both cardiac and noncardiac pathology--will have angiographically normal coronary arteries. While the prognosis of the group as a whole is excellent, successful management requires a clear understanding of the multiple and varied conditions that can cause this syndrome. PMID- 8443990 TI - Cardiogenic shock: elements of etiology, diagnosis, and therapy. AB - Cardiogenic shock usually is the result of marked depression in myocardial function. Rapid recognition and stabilization are essential if the patient is to survive. A variety of cardiovascular conditions can lead to cardiogenic shock; the most common of these is acute myocardial infarction. Once stabilization of the cardiogenic shock patient has been effected, hemodynamic monitoring and definitive therapy should be attempted if appropriate. Intra-aortic balloon counterpulsation is effective in stabilizing these patients temporarily. Definitive therapy may include surgical or catheterization interventions. Mortality, even under the best of circumstances, remains high. PMID- 8443991 TI - Effects of intracoronary administration of nitroglycerin on contralateral intracoronary acetylcholine test results. AB - This study examined the question of whether intracoronary administration of nitroglycerin modifies contralateral intracoronary acetylcholine test results. Acetylcholine was injected separately into both left and right coronary arteries in 63 patients with coronary spastic angina. Acetylcholine (20 and 50 micrograms) was injected first into the coronary artery responsible for the documented regional ischemia during spontaneous or induced attacks, and then into the other coronary artery. Coronary spasm was defined as severe transient coronary artery vasoconstriction with chest pain and/or electrocardiographic ischemic ST-segment deviation. Spasm was induced in either coronary artery in 60 patients (95%) and in both coronary arteries in 23 patients (37%). The frequency of induced spasm was 67% (42 of 63) in the coronary artery first challenged by acetylcholine. The coronary artery spasm subsided with the intracoronary injection of nitroglycerin (250-750 micrograms) in 19 patients. In the second challenge of intracoronary acetylcholine injection into the contralateral coronary artery, coronary spasm was induced in 29 (66%) of 44 patients. This was done without intracoronary administration of nitroglycerin in the first challenge and in 12 (63%) of 19 patients who had been given intracoronary nitroglycerin. The sensitivity for spasm induced by intracoronary acetylcholine appeared to be unaffected by nitroglycerin. Coronary spasm with ST-segment elevation by intracoronary acetylcholine in the second challenge was significantly less frequent in the patients receiving intracoronary acetylcholine in the second challenge was significantly less frequent in the patients receiving intracoronary nitroglycerin (first: 89%, second: 26%, p < 0.05) as well as in those not receiving intracoronary nitroglycerin for the spasm in the first challenge (first: 52%, second: 13%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8443992 TI - Functional health status in male patients without restenosis following successful PTCA. AB - In a prospective pilot study, subjective and objective parameters of the health status were assessed in 148 male patients (mean age 56 +/- 8.4 years) before and 4 months after successful coronary angioplasty (PTCA). Restenosis was defined as residual diameter stenosis > 50%. Although 96 patients (65%) had not developed restenosis at 4 months' invasive follow-up, subjective assessment of general well being was unchanged in 26% or worse in 71%; overall anginal status and exercise performance had however improved. Of 71 men younger than 60 years who had no restenosis at follow-up, 4 men retired and 13 remained on medical leave. The striking disparity between subjective and objective parameters was not related to significant differences of age, exercise capacity, and left ventricular ejection fraction, as well as to baseline characteristics (previous myocardial infarction, extent of coronary heart disease, comorbidity) compared with 52 patients with restenosis. Thus, despite documented sustained success after PTCA, the majority of patients failed to resume the status of subjective well-being. PMID- 8443993 TI - Noninvasive detection of coronary artery disease by assessing diastolic abnormalities during low isometric exercise. AB - The handgrip-apexcardiographic test (HAT) is a simple low-level (40% of maximal voluntary handgrip during 2 min) stress test which can detect left ventricular (LV) diastolic abnormalities. To determine whether it contributes to the diagnosis of coronary artery disease (CAD), HAT was obtained in 68 patients--47 with and 21 without angina pectoris--who prospectively underwent coronary arteriography. According to the highest or lowest individual values of diastolic apexcardiographic indices in 255 healthy volunteers, a pathologic or positive HAT was defined by the presence of at least one of the following new criteria: (1) A wave relative to total height of apexcardiogram during and/or after handgrip > 21%, (2) total apexcardiographic relaxation time (TART) during handgrip > TART at rest > 143 ms and/or TART corrected for the duration of diastole (TARTI) during handgrip < 0.14, or (3) diastolic amplitude time index (DATI), given by dividing TARTI and A wave relative to total diastolic amplitude of apex tracing during handgrip < 0.27. HAT was positive in 20 of 21 patients with single-vessel disease (sensitivity 95%), 21 of 24 patients with double-vessel disease (sensitivity 88%), and in 22 of 23 patients with triple-vessel disease (sensitivity 96%). Furthermore, HAT was positive in 20 of 21 (95%) patients without symptoms. Thus, the overall sensitivity of HAT for detecting CAD was 93%. This study is the first to demonstrate the high sensitivity of HAT in identifying patients with CAD with or without symptoms by assessing diastolic apexcardiographic abnormalities during low-level isometric stress. Thus, HAT potentially could become an additional simple diagnostic tool for noninvasive detection of patients with CAD. PMID- 8443994 TI - Electrocardiographic prediction of ejection fraction and site of LAD occlusion in anterior myocardial infarction. AB - Q-wave anterior myocardial infarctions due to occlusion of the left anterior descending artery (LAD) are generally associated with the most extensive left ventricular damage. The presence of abnormal Q waves on the electrocardiogram (ECG) provides important information to localize the site of left ventricular infarction. However, the relationship between abnormalities of the QRS morphology in the precordial leads and angiographic information such as ejection fraction and the site of LAD occlusion (before or after the first septal perforator) has not been studied extensively. Seventy-three patients with single-vessel disease with complete LAD occlusion, abnormal QRS morphology in leads V1-V4 on ECG, and abnormal wall motion with contrast ventriculography were studied retrospectively. LAD occlusions were proximal to the first septal perforator in 33 patients and distal in 40 patients. Q waves were present in 59 patients, and the other 14 patients had either minimal R waves (< 0.25 mm), poor R-wave progression, or R wave regression. A significantly higher ejection fraction was associated with the presence of R wave in V2 (0.52 +/- 0.18 vs. 0.39 +/- 0.15 in the absence of R wave, p < 0.003). LAD occlusion after and before the first septal perforator was associated with R wave in V2 in 67 and 36% of patients, respectively. Sensitivity and specificity of predicting occlusion after the first septal perforator based on R wave in V2 was 0.68 and 0.64, respectively. In patients with anterior myocardial infarctions, occluded LAD artery, and abnormal QRS morphology in the precordial leads, the presence of R wave in V2 is a useful predictor of higher ejection fraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8443995 TI - Isolated left posterior fascicular block: a reliable marker for inferior myocardial infarction and associated severe coronary artery disease. AB - The electrocardiographic (ECG) pattern of isolated left posterior fascicular block (LPFB) is a rare condition. It seems that true LPFB is often not recognized, whereas in cases of simple QRS axis of +60 degrees to +100 degrees in the frontal plane, the diagnosis of LPFB is made erroneously. Both facts rely on controversial and partially misleading opinions in the literature. Therefore, a retrospective and prospective study was performed in order to determine the prevalence of LPFB and to correlate its presence to the underlying disease. Retrospective study: Of a cohort of 830 patients referred in 1988 to a cardiologic laboratory for invasive investigation of certain or suspected coronary artery disease (CAD), 163 patients had an old inferior myocardial infarction (IMI). Nine patients (5.5%) showed the typical pattern of LPFB; eight of these had three-vessel disease. The diagnosis of IMI had been made only in one case before entry of the patient into the hospital, since LPFB generally masks IMI. Prospective study: 2502 ECGs were investigated, 1710 from a department of cardiology and 792 from two departments of internal medicine. Six LPFBs were detected (0.24%), all associated with IMI and four of them with three-vessel CAD. It is concluded that LPFB is a rare but clinically important intraventricular conduction disturbance. Its appearance is reliably connected with IMI and generally reflects severe three-vessel CAD, requiring invasive investigation. PMID- 8443996 TI - Myocardial infarction in Qatar: the first 2515 patients. AB - The data registry of all patients admitted between 1982 and 1990 to the Coronary Care Unit at Hamad General Hospital with the diagnosis of documented acute myocardial infarction is reviewed. We report a total of 2,515 patients (86.6% men and 13.4% women) with a mean age of 51 years (range 18-99). Of these, 62% were smokers, 29% had diabetes, and 20% had hypertension. The hospital mortality rate was 10%. The most significant factors associated with higher mortality were older age, female gender, and anteroseptal infarction. The age of 23% of the patients was 40 years or younger. Comparison between these younger patients (Group I) and those over 40 years (Group II) demonstrated that Group I had lower mortality (3.6%) than Group II (12%) (p < 0.001). Group I patients were predominantly men (96.8%), of Asian nationalities (71%), and usually smokers (78%). The observation that myocardial infarction occurs frequently in young Asian men needs further evaluation to identify specific risk factors. PMID- 8443997 TI - Electrocardiographic responses to jogging in middle-aged and older men and women. AB - Recent jogging-related sudden deaths rekindled the concern among health professionals as to the hazards of strenuous exercise. The purpose of this study was to evaluate the extent of rhythm disturbances and myocardial ischemia in older men and women during a typical strenuous jogging session. Twenty-two members of a local jogging club (11 men and 11 women) between the ages of 50 and 66 years participated in the study. The CardioData PR3/ST monitor was employed to record heart rate, rhythm disturbances, J point and ST slope during the course of the run. The men ran a 10 km run and the women a 6 km run at a competitive pace. The mean maximal heart rate during the run was 170 +/- 15 beats/min for the males and 176 +/- 14 beats/min for the females. The mean J point during the run was 3.39 +/- 1.21 mV for the males and -2.97 +/- 0.96 mV for the females. Females showed a significantly lower mean ST slope (3.95 +/- 0.91 mV) during the run than the males (5.56 +/- 1.37 mV, p < 0.05). A number of episodes of premature ventricular beats, both uni- and multifocal, were observed. Exercise testing of sufficient intensity is recommended to detect those persons susceptible to developing serious arrhythmias during strenuous exercise. PMID- 8443998 TI - New and combined sensors for adaptive-rate pacing. AB - A new potential indication for cardiac pacing is chronotropic incompetence, that is, an inadequate cardiac rate response to exercise and other metabolic demands. Many patients who have been paced for indications such as complete heart block or sick sinus syndrome also have chronotropic incompetence. Such patients are not adequately treated when fitted with a constant rate pacemaker. Adaptive-rate pacemakers increase the pacing rate in proportion to signals derived from a biosensor which is sensitive to exertion and possibly to other metabolic requirements. These pacemakers have proven valuable for patients with overt chronotropic incompetence. However, no single sensor/algorithm is ideal and improvement has been sought by introducing new sensors, adjusting the algorithms by which biosensor signals are converted to the most appropriate pacing rate, or by combining sensors in such a way that a composite biosensor signal is derived which bears a close linear relationship with the appropriate heart rate. An example of a new sensor is the accelerometer, which is sensitive to a fuller range of movements than the piezo crystal. A successful new algorithm is the rate augmentation algorithm for use with minute ventilation, which provides a better initial pacing rate response. A combination of minute ventilation sensed by impedance changes and movement sensed with piezo crystals maintains the rapid response from the piezo crystal and overcomes its lack of proportionality. Another successful new combination of sensors is QT sensing from the evoked ventricular potential and motion sensing with a piezo crystal. As yet, these innovations have not been exhaustively tested and shown to confer clinical benefit but the improvements are such that an advantage can be expected. PMID- 8443999 TI - Anatomy, histology, and pathology of the cardiac conduction system: Part I. AB - Normal anatomic and histologic features of the sinus node, atrial myocardium, and interatrial conduction of the cardiac impulse are reviewed. The controversy surrounding atrial conduction via specialized atrial cells versus specific internodal tracts (between sinus and atrioventricular nodes) is discussed. PMID- 8444000 TI - Transient left ventricular aneurysm in a patient with hypertrophic cardiomyopathy and myocarditis. AB - Left ventricular wall motion abnormalities, aneurysm formation, and progression to global hypokinesis have been described in patients with myocarditis and in patients with hypertrophic cardiomyopathy. We document a case of reversible aneurysm formation, cardiogenic shock, and complete recovery in a patient with myocarditis and hypertrophic cardiomyopathy. Pathophysiologic mechanisms of myocardial injury and recovery are discussed. PMID- 8444001 TI - Percutaneous mitral balloon valvotomy in a patient with coexistent mitral stenosis and hypertrophic cardiomyopathy. AB - A patient with coexistent mitral stenosis and hypertrophic cardiomyopathy is described, in whom symptoms related to impaired left ventricular diastolic filling improved after successful percutaneous mitral balloon valvotomy. PMID- 8444002 TI - Polymorphism of the cardiac manifestations in dermatomyositis. AB - Cardiac involvement in polymyositis and dermatomyositis usually is asymptomatic and rarely the principal clinical feature at the time of initial presentation. We describe a patient with dermatomyositis who presented with overt acute pericarditis which has not, to our knowledge, been previously reported. Acute pulmonary edema resulting from documented acute myocarditis developed during a second exacerbation. Long-term follow-up failed to demonstrate new cardiac complications during subsequent exacerbations, adding to the known polymorphism of the heart involvement in these systemic disorders. PMID- 8444003 TI - Spontaneous secure reimplantation of a dislodged pacemaker electrode onto the right ventricular outflow tract, reestablishing a sufficient pacing condition. AB - A 62-year-old woman underwent cardiac pacemaker implantation for sick sinus syndrome with bradycardia, and the tip of an endocardial tined lead was positioned to the right ventricular apex. On the fifth postoperative day, an incomplete pacing failure, lasting about 10 min, was observed transiently on 24-h monitoring. This event, however, was not considered to be a clinical manifestation of the ensuing complication until the patient visited our pacemaker clinic 2 months postoperatively. At that time, a chest x-ray demonstrated that the electrode tip had migrated markedly to the right ventricular outflow tract (RVOT), but presented a sufficient pacing condition. The reimplantation site appeared to be very insecure for pacing, raising the potential risk of repeat dislodgement since the lead was not provided with a helix. At the second operation, performed to assess the problem, the ventricular excitation threshold measured at 1.3 V with a 0.5 ms pulse width. Furthermore, it was unexpectedly disclosed that the electrode tip was so tightly anchored at the site that it could not be withdrawn, eliminating the possibility of repeat dislodgment. Consequently, the entire original pacing system could be used as before and no further complications were observed. Although the situation encountered was very rare and seemed to be problematic, careful observation might be an alternative to surgical intervention even when a tined tip without helix has been used. PMID- 8444004 TI - Exercise-induced ventricular tachycardia: a rare manifestation of digitalis toxicity. AB - Digitalis intoxication is one of the most common adverse drug reactions. Although some arrhythmias are seen more frequently than others, virtually any rhythm disturbance, including ventricular tachycardia, may occur. However, to our knowledge, exercise-induced ventricular tachycardia as a complication of digitalis therapy has never been described before. This case presents a patient with a digitalis-induced ventricular tachycardia occurring exclusively during exercise. PMID- 8444005 TI - Rene-Joseph-Hyacinthe Bertin. PMID- 8444006 TI - Development of lipophilic anticancer agents for the treatment of brain tumors by the esterification of water-soluble chlorambucil. AB - The lipophilic derivatives of the anticancer alkylating agent chlorambucil, chlorambucil-methyl, -isopropyl and -tertiary butyl esters, were synthesized and administered i.v. to anesthetized rats. Plasma and brain concentrations of these agents and of their active metabolites, chlorambucil and phenylacetic mustard, then were determined by high-performance liquid chromatography between 5 and 60 min. Whereas large amounts of chlorambucil-tertiary butyl ester entered and were maintained in brain, lower amounts of chlorambucil-isopropyl ester and no chlorambucil-methyl ester were found in brain. The comparative brain/plasma concentration-time integral ratios of the total active agents generated from chlorambucil-tertiary butyl, -isopropyl and -methyl esters were 0.85, 0.12 and 0.06, respectively, compared to a ratio of 0.02 for chlorambucil. In vitro alkylating activity of each ester was compared to that of equimolar chlorambucil, by reaction with 4-(p-nitrobenzyl)pyridine. Each ester possessed high intrinsic alkylating activity, equal to 38.4, 57.0 and 69.9% of chlorambucil activity, for the -tertiary butyl, -isopropyl and -methyl esters, respectively. Therefore each is an active antineoplastic agent irrespective of whether or not chlorambucil is regenerated. The rates of ester hydrolysis of these derivatives to chlorambucil were measured in fresh rat blood and in liver and brain homogenates at 37 degrees C. Chlorambucil-methyl and -isopropyl esters were hydrolysed quickly within 30 s in blood and liver, whereas chlorambucil-tertiary butyl ester was more stable with half-lives of approximately 7 h and 2 h, respectively. All proved to be relatively stable in brain homogenate. Steric hindrance around the ester linkage of chlorambucil-tertiary butyl ester reduces its affinity to and rate of hydrolysis by plasma and liver esterases, and allows it to accumulate within the brain. Chlorambucil-tertiary butyl ester maintains high levels in brain despite rapidly declining plasma concentrations and, due to these favorable pharmacokinetics and to its intrinsic anticancer activity, it possess promising characteristics for the treatment of malignant brain tumors. PMID- 8444007 TI - Intravenously injected radiolabelled fatty acids image brain tumour phospholipids in vivo: differential uptakes of palmitate, arachidonate and docosahexaenoate. AB - This paper investigates the incorporation of intravenously (i.v.) administered radiolabelled fatty acids--[9,10(3)-H]palmitate (3H-PA), [1-14C]arachidonate (14C AA) and [1-14C]docosahexaenoate (14C-DHA)--into intracerebrally implanted tumours in awake Fischer-344 rats. A suspension of Walker 256 carcinosarcoma tumour cells (1 x 10(6) cells) was implanted into the right cerebral hemisphere of 8- to 9 week-old rats. Seven days after implantation, the awake rat was infused i.v. for 5 min with 3H-PA (6.4 mCi/kg), 14C-AA (170 microCi/kg) or 14C-DHA (100 microCi/kg). Twenty minutes after the start of infusion, the rat was killed and coronal brain sections were obtained for quantitative autoradiography and histology. Each fatty acid showed well-demarcated incorporation into tumour tissue. Areas of necrosis or haemorrhage showed no or small levels of incorporation. The ratios of incorporation into the tumour to incorporation into contralateral brain regions were 2.8-5.5 for 3H-PA, 2.1-3.3 for 14C-AA and 1.5 2.2 for 14C-DHA. The mean ratios differed significantly between the fatty acids (P < 0.01). 3H-PA was not incorporated into necrotic tumours despite the presence of an open blood-tumour barrier, indicated by extravasated horseradish peroxidase. The incorporation rate constant of 3H-PA was similar for small intracerebral and large extracerebral tumours. The results show that 3H-PA, 14C AA and 14C-DHA are incorporated more readily into tumour tissue than into brain, and that the increase is primarily due to increased utilization of fatty acids by tumour cells and not due to a high blood-tumour permeability. The relative increases in rates of incorporation for the different fatty acids may be related to lipid composition of the tumour and to the requirement of and specific role of these fatty acids in tumour cell growth and division. PMID- 8444008 TI - The role of fibronectin in tumor implantation at surgical sites. AB - Fibronectins are a family of glycoproteins with modular functional domains. They mediate cell-cell and cell-matrix interactions which are important in embryogenesis, wound healing, metastasis and other processes. We present data on the influence of fibronectin on wound implantation of a murine mammary carcinoma line, TA3Ha. Fibronectin used in these studies was derived from bovine plasma, human serum, human foreskin fibroblasts, and mouse embryo cultures. TA3Ha cells rarely form tumors in the liver of syngeneic mice when injected intravenously but after hepatic wedge resection, 45% (107/240) of the mice develop tumors in the hepatic wound. Wound implantation is markedly reduced when the cells are pre exposed to 200 micrograms/ml bovine plasma fibronectin (13%, P = 0.007), human serum fibronectin (0%, P = 0.02), human cellular fibronectin (0%, P = 0.02), or mouse cellular fibronectin (0%, P = 0.04). Lung colonization is also reduced by these fibronectins. These effects are not due to a cytotoxic action of fibronectin, since intraperitoneally injected fibronectin-treated cells form ascites tumor as effectively as do control untreated cells. Local application of a solution containing 0.25 mg/ml mouse cellular fibronectin to the hepatic wound reduces the frequency of tumor implantation from 45% to 5% (1/21, P = 0.001). No tumor implantation inhibition is seen when only suspending medium or albumin in suspending medium is used. The mechanism by which topical application of fibronectin reduces hepatic wound implantation of tumor cells is unclear, but this finding raises an exciting possibility of preventing local recurrence of cancer. PMID- 8444009 TI - Human and murine Kupffer cell function may be altered by both intrahepatic and intrasplenic tumor deposits. AB - The liver is the most common site of hematogenous metastases from colorectal carcinoma. Kupffer cells (KC), which line the hepatic sinusoids, may form the first line of defense against circulating tumor cells. The purpose of this study was to determine the effect of hepatic metastases and intra-abdominal tumor growth on KC binding of human colorectal carcinoma (HCRC) cells. MIP-101, a poorly metastatic cell line, and CX-1, a highly metastatic cell line, were injected intrasplenically into nude mice and KC were isolated by collagenase perfusion at varying intervals after injection. Conditioned media were collected from MIP-101, CCL 188 and CX-1 to determine their in vitro effect on KC function. KC from MIP-101 injected mice (14% liver metastases, 100% splenic tumors) bound a significantly greater number of MIP-101 and clone A cells than CX-1 cells in vitro. KC isolated from mice 5 weeks after CX-1 injection (100% liver metastases) also showed increased binding of MIP-101 and clone A cells compared to CX-1 cells. Similar results were obtained when tumor cell binding to normal human liver KC was compared to binding to KC from human livers from patients with hepatic metastasis from colorectal cancer. In contrast KC obtained from mice 3 weeks after CX-1 injection (44% liver metastases) showed significantly decreased binding of MIP-101 and clone A cells. The conditioned medium from CX-1 cells significantly decreased the in vitro binding of both MIP-101 and CX-1 by KC. These results indicate that the ability of KC to bind HCRC cells (which precedes phagocytosis and tumor cell killing) is a dynamic function and affected by concomitant tumor growth. HCRC cells may alter KC function via the production of specific tumor-derived soluble factors. In order to devise new and more effective therapeutic options in the treatment of liver metastases the nature of this tumor cell-KC interaction must be better understood. PMID- 8444010 TI - Expression of activated gelatinase in human invasive breast carcinoma. AB - The expression of both 92- and 72-kDa gelatinases has been studied in 20 samples of human breast carcinoma by the technique of gelatin zymography. This technique allowed the relative amount of each gelatinase to be determined in small samples of tissue (< 10 mg). More importantly, active and latent forms of the two gelatinases were resolved. Two samples (10-20 mg) were cut from each piece of tumour in order to monitor the variability of gelatinase distribution within that section of tumour. The 72-kDa latent progelatinase was present in 15 of the 20 tumours, with trace amounts in two others. The 62-kDa activated form of this gelatinase was detected in all 15 of the tumours in which the latent form was present. The 92-kDa latent progelatinase was present in 11 of the 20 tumours, with trace amounts in four others. However, the 82-kDa activated form of this gelatinase was only clearly detected in two tumours, although three others showed the presence of trace amounts. The ratio of active to latent forms of the 72-kDa gelatinase ranged from 0.9 to 3.6. There were no marked correlations between gelatinase expression and established staging and prognostic markers. Analysis of three samples of fibroadenoma revealed only very low levels of gelatinase expression. On the basis of these results, activation of the 72-kDa progelatinase appears to be a more common event in invasive breast carcinoma than activation of the 92-kDa progelatinase. However, neither proteinase showed a correlation with metastatic progression, as measured by lymph node involvement. PMID- 8444011 TI - Alcohol consumption suppresses metastasis of B16-BL6 melanoma in mice. AB - Female C57BL/6 mice were fed a defined, pelleted diet and given 10% w/v or 20% w/v ethanol in their drinking water. Natural killer (NK) cell cytolytic activity was compared between water-drinking and ethanol-consuming mice and in mice that were also treated with polyinosinic-polycytidylic acid (poly I:C) to augment NK cell activity or with anti-NK1.1 antibody to decrease activity. NK cell cytolytic activity was not altered in mice given 10% ethanol, but was decreased in mice given 20% ethanol compared to water-drinking mice. Poly I:C treatment increased and anti-NK1.1 antibody treatment decreased NK cell activity in both water drinking and 20% ethanol-consuming mice. Experimental and spontaneous metastases of B16-BL6 melanoma were evaluated as a function of the duration of ethanol consumption before tumor inoculation and as a function of altered NK cell activity. Experimental metastasis was inhibited after 4 and also after 6.5 weeks of ethanol exposure. Poly I:C treatment inhibited tumor lung colonization irrespective of ethanol consumption. Anti-NK1.1 antibody treatment increased metastasis, although to a lesser degree in mice consuming 10% ethanol. Spontaneous metastasis was inhibited in mice consuming 10% ethanol for 4 weeks, and in mice consuming 20% ethanol for 1 and 4 weeks before melanoma inoculation. PMID- 8444012 TI - U-77,863: a novel cinnanamide isolated from Streptomyces griseoluteus that inhibits cancer invasion and metastasis. AB - Several cinnamoyl compounds have been shown to have antitumor activities, but not specifically anti-invasive or antimetastatic effects. U-77,863 (o-methyl cinnanamide) was originally isolated from a fermentation beer of Streptomyces griseoluteus and recently synthesized (Harper, DE and Welch DR. Journal of Antibiotics, in press). Based upon some differential activities of cinnanamides, in general, and U-77,863, specifically, we tested the hypothesis that U-77,863 could inhibit invasion and metastasis of human malignant melanoma cell lines C8161 and A375M. Pretreatment of melanoma cells in vitro with nontoxic doses of U 77,863 caused a dose-, and time-dependent, reversible reduction (IC50 = 12.5 micrograms/ml) of invasion through Matrigel-coated polycarbonate filters in the Membrane Invasion Culture System (MICS). Likewise, lung colonization was significantly (P < 0.05) inhibited when tumor cells were pretreated in vitro with U-77,863 prior to intravenous injection. Structure-activity analysis revealed that the acrylamide side-chain alone and cinnanamide were only slightly less potent than U-77,863, whereas cinnamic acid analogs did not inhibit tumor cell invasion at doses < or = 100 micrograms/ml. U-77,863 inhibits invasion and metastasis without decreasing growth rates or clonogenic potential. Adhesion to endothelial monolayers or extracellular matrices (Matrigel) is not affected by exposure to U-77,863. U-77,863 presumably inhibits metastasis by inhibiting tumor cell extravasation (invasion). U-77,863 is a lead compound for developing a novel class of anti-invasive/anti-metastatic drugs. PMID- 8444013 TI - High dose dexamethasone and base of brain irradiation for hormone refractory metastatic carcinoma of the prostate. AB - High dose dexamethasone combined with irradiation to the base of the brain achieved a dramatic beneficial effect in two terminal cases of widespread metastatic carcinoma of the prostate involving cranial nerves and the entire skeleton. Pain requiring very large doses of analgesics and anemia requiring blood transfusions every 3-4 weeks were improved rapidly. No further transfusions were needed. PMID- 8444014 TI - Contributions of olfaction to maternal aggression in laboratory rats (Rattus norvegicus): effects of peripheral deafferentation of the primary olfactory system. AB - We examined the effects in postpartum female rats (Rattus norvegicus) of olfactory deafferentation by intranasal ZnSO4 on maternal aggression and retention of aggression 24 hr after pups are removed. When females were tested with pups, effects of deafferentation depended on postpartum interval; anosmia failed to reduce aggression on Lactation Day 3 (L3), but anosmia was associated with moderate reductions on L8-L12. We propose that postpartum aggression is stimulated initially by hormonal factors associated with late pregnancy but later is supported by exteroceptive stimulation. After removal of pups, although aggression scores were lower across treatment conditions, anosmic females had shorter latencies to attack and tended to elicit more submissive behavior from intruders. Data suggest that odor cues from conspecifics normally inhibit aggression by females, but this inhibition is reduced during lactation. PMID- 8444015 TI - Responses to escalating predatory threat in garter and ribbon snakes (Thamnophis). AB - Several models suggest that animals perform a stable sequence of responses during increasing threat from a potential predator. To test the comparative utility of such models, 45 garter and ribbon snakes from four species (genus Thamnophis) were given an antipredator behavior test in which the snakes were exposed to a series of five levels of escalating threat: (a) threat is out of view, (b) threat looms over arena, (c) threat is nonmoving human hand near snake's head, (d) threat is moving human hand, and (e) threat is experimenter's tapping the snake's body. Five different antipredator behaviors were measured. It was found that both qualitative and quantitative changes in behavior occurred between threat levels. However, species differences were also found in the occurrence and amount of every behavior recorded, which indicates that even closely related species may differ in behaviors exhibited in different phases of a predatory encounter. PMID- 8444016 TI - Discrimination of duration ratios by pigeons (Columba livia) and humans (Homo sapiens). AB - Humans (Homo sapiens) were trained on 2 versions of a 2-alternative, forced choice procedure. First, subjects judged which of 2 successive stimulus durations was longer. Second, subjects judged whether the ratio of the 2 durations was less or greater than a criterion ratio (e.g., 2:1). Accuracy was significantly lower for the task in which the judgment was made according to the ratio of the 2 durations. This result is different than that obtained by Fetterman, Dreyfus, and Stubbs (1989), who trained pigeons (Columbia livia) on a similar pair of tasks and found that pigeons' performance was comparable for the 2 discriminations. Comparisons of the pigeon and human data suggest that humans were more accurate than pigeons when the judgment involved which duration was longer, but that accuracy was comparable for the ratio-based task. PMID- 8444017 TI - Development of combinatorial manipulation in infant baboons (Papio cynocephalus anubis). AB - Infant baboons (Papio cynocephalus anubis) housed in individual cages combined objects and used tools in play and food acquisition. The baboons first combined objects at age 2 months, placed objects inside a container at age 4 months, and repeatedly used paper towels as sponges at age 6 months. The results of this investigation demonstrate that infant baboons develop extensive manipulative propensities during the first postnatal semester. These data are consistent with hypotheses that (a) creative recombination facilitates the acquisition of novel behavior patterns and (b) the development of combinatorial manipulation in baboons parallels the development of analogous abilities in human infants. PMID- 8444018 TI - Exposure to various stressors alters preferences for natural odors in rats (Rattus norvegicus). AB - Male Sprague-Dawley rats (Rattus norvegicus) were given choice tests (Test 1) in a maze with the odors of clean bedding, citronella, an alpha colony (ACO), shocked conspecifies (SCO), or a predator cat (PCO). In Experiments 1-3, groups were exposed to no stress, defeat by a conspecific, or shocks. During subsequent tests (Test 2), nonstressed rats showed no change in odor preferences; defeated rats showed a nonsignificant reduction in preference for ACO; and shocked rats showed significant preference reductions for SCO and PCO and a significant increase in preference for ACO. In Experiment 4, odors of isolated, nonstressed conspecifics (CO) were preferred more than ACO, for rats given shock before Test 2. In Experiment 5, rats significantly preferred CO over ACO when exposed to a caged cat during Test 2. Because of exposure to stress, rats later avoided certain fear odors and showed strong preferences for the odors of nonstressed conspecifics. PMID- 8444019 TI - Perception of conspecific faces by budgerigars (Melopsittacus undulatus): II. Synthetic models. AB - Perception of faces by budgerigars (Melopsittacus undulatus) was studied with computerized images modeled after natural faces. Individual facial characteristics were varied with all others held constant; then relative importance among several features was determined by varying each within a single experiment. Characteristics with the potential to signal important biological information (e.g., age or sex) were perceptually salient, whereas characteristics that vary among faces but have limited potential to signal important information were not. Model faces were also presented in a normal or an altered configuration. Birds discriminated among faces in a normal configuration more easily than among models with an altered configuration even when the facial features on which the discrimination was based differed in the same way; this suggests that configurational cues play an important role in face perception by budgerigars. PMID- 8444020 TI - Maternal contributions to sensory experience in the fetal and newborn rat (Rattus norvegicus). AB - Using videographic analyses, we identified and quantified maternal contributions to the sensory environment of the perinatal rat (Rattus norvegicus) by analyzing, from the offspring's perspective, the dam's activities during gestation, labor, and delivery. Our observations indicate that pregnant females remain highly active during the final week of gestation, as compared with nonpregnant control animals. Exploratory movements, feeding, drinking, self-grooming, and other activities of the rat dam pitch, turn, accelerate, and expose fetuses to mechanical pressures. During parturition uterine contractions and maternal licking and handling provide vigorous tactile and vestibular stimuli to pups. Newly born pups are exposed to intense thermal stimulation, cooling rapidly to the temperature of the postnatal environment. Our results suggest that fetal and newborn rats are exposed during development to a broad range of maternally produced stimuli. PMID- 8444021 TI - Use of multiple-alternative matching-to-sample in the study of visual search in a chimpanzee (Pan troglodytes). AB - Visual search in a chimpanzee (Pan troglodytes) and in humans (Homo sapiens) were compared under the multiple-alternative matching-to-sample (MTS) procedure, in which a sample stimulus was followed by one positive (target) and several negative comparison stimuli (distractors). Reaction times in the chimpanzee were affected by the number of distractors, the target-distractor similarity, and the uniformity of search display. Similar results were also obtained from humans and suggest that the performance by the chimpanzee may involve the same visual information-processing capabilities as those required in the human visual search performance. The multiple-alternative MTS is useful for studying various visual perceptual-cognitive abilities of animals including chimpanzees. PMID- 8444022 TI - Assessment of attachment in differentially reared infant monkeys (Macaca radiata): response to separation and a novel environment. AB - To assess the developmental consequences of rearing environments for 12 infant bonnet macaques (Macaca radiata), infants from 2 environments, either low foraging demand (LFD) or variable foraging demand (VFD) for their mothers, were observed under 2 test conditions after the completion of the differential rearing treatment. One of the test conditions involved introduction of the rearing cohorts to a novel room; this was done in two series of four 1-hr sessions, a series before and a series after completion of the 2nd test condition. The 2nd test condition involved a 20.5-hr removal of each mother from the rearing cohort; this was repeated once a week for 3 weeks. The results of the novel room tests effectively differentiated rearing treatments in this study and suggested treatment group differences in attachment security. In contrast, the maternal separations failed to differentiate rearing treatments. PMID- 8444023 TI - Behavioral development and strain differences in perinatal mice (Mus musculus). AB - The perinatal development of spontaneous body movements and reflexes was examined in Slc:ICR, C3H/He, and BALB/c mice (Mus musculus). Mice were observed from Day 18.0 (a day before normal parturition) to Day 21.5 of gestation. The developmental changes of spontaneous body movements and reflexes occurred quickly. Strain differences in behavioral development were detected in the duration of spontaneous body movements but not in the occurrence of reflexes. Hybrid mice were more active than their parental strains with regard to duration of spontaneous body movements. The rooting reflex and crossed extensor reflex in hybrid mice occurred more frequently on Day 18.0 than in their parental strains. There was no maternal effect between reciprocal hybrid mice. These results indicate that the perinatal period is characterized by quick qualitative and quantitative changes in behavioral development and by the appearance of these genetic differences. PMID- 8444024 TI - Effects of sex steroids on maternal motivation in the common marmoset (Callithrix jacchus): development and application of an operant system with maternal reinforcement. AB - We developed an operant paradigm for measuring effects of reproductive steroids on maternal motivation in common marmosets (Callithrix jacchus). Conditioned response regulated females' exposure to maternal reinforcement. Nulliparous females (n = 15) with experience with infants in social groups were subjects. The paradigm was validated by examining (a) effects of reinforcing stimuli on affective behavior in a nonoperant paradigm, (b) responsiveness of operant performance to changes in reinforcing stimuli and reinforcement schedule, (c) changes in operant responding due to omission of reinforcement, and (d) relation between operant responding and species-typical maternal behavior. In pregnant females, (n = 4), frequency of bar pressing and estradiol:progesterone ratio were maximal just before birth. Nonpregnant females (n = 3) treated with progesterone and estradiol to mimic late-pregnancy steroid profiles showed increased operant maternal behavior. PMID- 8444025 TI - Xconf: a network-based image conferencing system. AB - People often need to get together to share and discuss small amounts of image and textual data, but this is difficult when they are not located in the same place. One solution to this problem is Xconf, a multimedia computer conferencing groupware tool using existing national and international networks (the Internet). Simultaneous conferencing supports real-time interaction between multiple remote computer displays. Xconf multimedia may include conversational text, images, pointers to objects in images, and group execution of programs. Conferencing may take place with or without images. Interaction is tightly coupled with all users aware of global changes to the shared session and alternatively, individuals may monitor a specific subgroup of other users to concentrate on what they are discussing. Collaborative groups who have access to both computer networks and networked based X-Window System graphics displays can participate in a conference. Xconf is an X-Window "client" program which provides multimedia conferencing support for a group of X-Window displays. Because it is centralized, no software other than the standard X-Window System is required on any of the participants display systems. Key data structures and algorithms for image conferencing are present. PMID- 8444026 TI - An accelerative enumeration algorithm for the bottle combination problem and the menu planning problem. AB - In the clinical practice, there are a number of instances in which the request tailored to each patient must be satisfied with a combination of ready-made medical supplies. For example, in intravenous infusion and feeding, an appropriate combination of commercially available bottles must be chosen such that fluid, electrolyte, and nutritional requirements can be satisfied for the individual patient. Menu planning also has the same feature. However, the problem of the optimal combination of medical supplies is difficult to solve exactly and quickly even with the aid of the computer, because of the combinatorial nature of this problem. We formulate the combinatorial problem of medical supplies as a nonlinear all-integer programming problem and present a fast exact algorithm to solve the problem. The proposed algorithm is proved to find an optimal combination in an acceptable calculation time for medical problems of the usual size. PMID- 8444027 TI - Characterization and elimination of AC noise in electrocardiograms: a comparison of digital filtering methods. AB - Diverse digital methods have been advanced previously to remove power line (AC) interference in the ECG. Representative notch filters, adaptive filters and a globally derived filter are surveyed in this study; their performances are compared on artificial signals as well as actual ECGs. The ECGs, recorded at four European medical centers, are from the Common Standards in Electrocardiography (CSE) ECG tape library. AC interference in these ECGs is shown to exhibit two qualities especially relevant to filter design: considerable deviations from a nominal 50 Hz frequency and substantial noise at higher harmonics. Some criteria and useful quantitative measures are suggested to evaluate AC digital filters. PMID- 8444028 TI - Computation of the uniform minimum variance unbiased estimator of a normal mean following a group sequential trial. AB - The sampling distribution of data collected in a group sequential trial is such that the usual fixed-sample estimates of treatment effect are biased. Improved estimates can be obtained by taking the group sequential stopping rule into account. In particular, in the case of inference about the mean of a normal distribution, the sample mean is no longer the uniform minimum variance unbiased estimator (UMVUE). In this paper, I present a way in which the UMVUE for a normal mean can be calculated using software capable of determining the operating characteristics of a group-sequential test. PMID- 8444029 TI - A comparison of logistic regression to decision-tree induction in a medical domain. AB - This paper compares the performance of logistic regression to decision-tree induction in classifying patients as having acute cardiac ischemia. This comparison was performed using the database of 5773 patients originally used to develop the logistic-regression tool and test it prospectively. Both the ability to classify cases and the ability to estimate the probability of ischemia were compared on the default tree generated by the C4 version of ID3. They were also compared on a tree optimized on the learning set by increased pruning of overspecified branches, and on a tree incorporating clinical considerations. Both the LR tool and the improved trees performed at a level fairly close to that of the physicians, although the LR tool definitely performed better than the decision tree. There were a number of differences in the performance of the two methods, shedding light on their strengths and weaknesses. PMID- 8444030 TI - "On analytical methods and inferences for 2 x 2 contingency table data from medical studies" by Engeman and Swanson--a comment. PMID- 8444031 TI - [Peleska and his associates or cardiac pacing in Krc]. PMID- 8444032 TI - [New findings in vascular diseases]. PMID- 8444033 TI - [Implantation of coronary stents--review of modern knowledge]. PMID- 8444034 TI - Czechoslovak cardiology. AB - Review of major activities in Czechoslovak cardiology before the second world war and afterwards until the present time. International relations, achievements, problems and failures were closely linked with the Czechoslovak Society of Cardiology, established in 1929. PMID- 8444035 TI - Strategies for primary coronary heart disease prevention. AB - With increasing knowledge of coronary heart disease (CHD) epidemiology, it has become apparent that preventive treatment of high-risk individuals--the high-risk strategy--will reduce individual risk but is insufficient by itself to reduce the burden of CHD in the population as a whole because more than half of the future victims of CHD have risk factor levels below the high range, leaving these persons unprotected. Since the relationship between risk factors and clinical CHD risk is continuous in most instances, without a sharp dividing line between high and low risk, the aim of optimal preventive action must be to shift the entire risk factor distribution curves to the left, in order to reduce the number of persons in the upper end of the distribution on the right. The strategy designed to effect this shift is the community strategy which requires that the whole population adopts preventive measures, i.e. makes changes in lifestyles, especially as regards diet, smoking habits, daily exercise and patterns of stress which favour unhealthy habits or may be harmful in themselves. The two strategies are not alternatives but complementary and, for optimal effectiveness, must be carried out simultaneously in the community. It can be shown that the combined strategy is more effective than either strategy alone. Each of the strategies has on comparison its own particular strengths, adding up to create a community climate favourable for prevention. The practicing physician is primarily concerned with the high-risk strategy but also plays an essential role in providing active support for the community strategy through giving preventive advice on health-promoting living habits to all of his patients and their families. PMID- 8444036 TI - Following PTCA exercise tolerance is only moderately correlated with cinevideo densitometric measurement of restenosis. AB - There is a pressing need for a non-invasive marker of restenosis following percutaneous transluminal coronary angioplasty. Computerised measurement of restenosis has not been used in conjunction with exercise test variables reflecting maximum exercise capacity. Thus we investigated thirty consecutive patients undergoing repeat coronary angiography for restenosis who had a satisfactory symptom limited exercise test. Exercise test variables namely ST segment depression, maximum exercise tolerance and rate/pressure product were correlated with the percentage stenosis measured by videodensitometry. Maximum exercise tolerance expressed in metabolic equivalents was correlated with restenosis severity (correlation coefficient -0.52, p = 0.003) as was maximum duration of exercise (correlation coefficient -0.46, p = 0.01). Maximum ST segment depression on exertion was not correlated with the degree of restenosis. In assessing patients after angioplasty exercise tolerance is related to the severity of restenosis. However the degree of variation within this relationship is such that it cannot be used confidently in the clinical setting to predict restenosis. PMID- 8444037 TI - Adenosine triphosphate in the treatment of supraventricular tachycardia. AB - The efficacy of adenosine triphosphate (ATP, Spofa) in controlling supraventricular tachycardia (SVT) was assessed in a group of 20 consecutive patients with this condition. Sinus rhythm was restored in a total of 19 patients (95% efficacy). SVT termination was followed, in a full 40% of patients, by asystole with a mean duration of 8.6 seconds; there were, however, no sequelae and no measures had to be taken. ATP can be regarded as a welcome addition to the current range of pharmacological options available for the treatment of SVT. PMID- 8444038 TI - [The intima of the common carotid artery in patients with hyperlipoproteinemia]. AB - Using sonography, the common carotid artery was examined in patients with hyperlipoproteinaemia and in controls. In 21 controls, the intima was present in 62%, intimal thickness was 0.41 +/- 0.14 mm. In patients with familial hypercholesterolaemia free of ischaemic heart disease (46 patients), the intima was demonstrable in 89%, intimal thickness was 0.74 +/- 0.21 mm. In patients with ischaemic heart disease (19 patients), the intima could be demonstrated in 100%, its thickness was 0.84 +/- 0.31 mm. In 21 patients with familial combined hyperlipoproteinaemia, the intima was present in 90%, intimal thickness was 0.73 +/- 0.17 mm. Intimal thickness was significantly greater (p < 0.001) in all groups of patients with hyperlipoproteinaemia than in the control group. A significant correlation between cholesterol levels and intimal thickness (p < 0.01) was demonstrated. PMID- 8444039 TI - [Variation in the R-R intervals on the electrocardiogram. A new diagnostic method in cardiology]. AB - Periodic heart rate fluctuation depends on the oscillation of sympathetic and vagal activation of the heart. Periodic retardation and acceleration of heart rate related to respiration and to blood pressure changes can be registered on the ECG as the "variability of R-R intervals". Testing procedures of the variability of R-R intervals at rest, during deep breathing, daily activities, during exercise and other stress tests are described in the paper. For the evaluation of the R-R interval's variability, current statistical methods are used (e.g. mean with standard deviation, variation coefficient, mean beat to beat differences in R-R intervals etc.). Power spectral analysis in the variability of 200-600 successive R-R intervals commonly performed today uses either rapid Fourier transformation or the autoregulation model. The analysis shows high- and low frequency peaks corresponding to the rapid and slow oscillations in heart rate. Evaluation of the R-R interval variability, especially using power spectrum analysis, gave good results in testing drugs, e.g., beta blockers, calcium antagonists and antiarrhythmic drugs. Variability of R-R intervals is reduced in conditions affecting the cardiac autonomous nervous system such as diabetes. It is also decreased in patients with ischaemic heart disease and in those with cardiac failure of different aetiology. The decrease is not an expression of the disease itself: it shows an alteration in neurovegetative tonicity in the particular disease condition. The decreased variability of R-R intervals in patients with ischaemic heart disease has an important prognostic value. The predominance of the sympathetic over the depressed vagal activity signalizes an increased risk of sudden coronary death. PMID- 8444040 TI - [Cardiac myxoma--morphology, clinical observations, diagnosis]. AB - The authors, presenting a group of 23 cardiac myxomas over the past 20 years, provide a review of the most common clinical symptoms, such as mitral valve stenosis, dyspnoea, tachycardia, and/or myxoma mass embolizing the systemic circulation as well as the diagnostic modalities available, echocardiography and angiography in particular. Based on the histologic picture and the ultrastructure. They assume that, histogenetically, cardiac myxomas are true neoplasms from undifferentiated mesenchymal cells. Echocardiographic confirmation of cardiac myxomas warrants immediate surgical removal of the neoplasm. PMID- 8444041 TI - Transcription termination. AB - Chromosomes are organized into units of expression that are bounded by sites where transcription of DNA sequences into RNA is initiated and terminated. To allow for efficient stepwise assembly of complete transcripts, the transcribing enzyme (RNA polymerase) makes a stable complex with the DNA template until it reaches the terminator. Three general mechanisms of transcription termination have been recognized: one is by a spontaneous dissociation of the RNA at a sequence segment where RNA polymerase does not maintain its usual stable interaction with the nascent chain; another involves the action of a protein (rho factor in bacteria) on the nascent RNA to mediate its dissociation; and a third involves an action triggered by a protein that binds to the DNA at a sequence that is just downstream of the termination stop point. Transcription termination is important in the regulation of gene expression both by modulating the relative levels of various genes within a single unit of expression and by controlling continuation of transcription in response to a metabolic or regulatory signal. PMID- 8444042 TI - Proline-dependent structural and biological properties of peptides and proteins. AB - Proline residues confer unique structural constraints on peptide chains and markedly influence the susceptibility of proximal peptide bonds to protease activity. This review presents a critical analysis of peptidases involved in the cleavage of proline-containing peptide bonds, with particular attention to the role of proline peptidases in the regulation of the lifetime of biologically active peptides. Peptidases discussed include aminopeptidase P, prolidase, dipeptidyl peptidase IV, prolyl endopeptidase, and prolyl iminopeptidase. Attention is also given to HIV-1 protease, because this key enzyme processes an Xaa-Pro peptide bond. Analysis of the above enzymes reveals that they may function as key pacemakers in the control of the activity of many peptide hormones and that they are involved in a variety of immunological processes, including T-cell-mediated immune response. The novel occurrence of cis-trans isomerization about Xaa-Pro bonds and the biological function of peptidyl-prolyl cis-trans isomerases (immunophilins) are reviewed. PMID- 8444043 TI - Cost of American medical care. PMID- 8444044 TI - Aquagenic pruritus. PMID- 8444045 TI - A dermatologic diary. Portrait of a practice. PMID- 8444046 TI - Guttate psoriasis. AB - Prevention and early treatment with appropriate antibiotics administered at the onset of upper respiratory infections in children with psoriasis may be able to block the appearance of acute guttate psoriasis. A careful screening for a focus of infection is also indicated, especially in children. PMID- 8444047 TI - Tuberous sclerosis: recent advances for the clinician. PMID- 8444048 TI - Acral erythema: a clinical review. AB - Acral erythema is a localized chemotherapy-induced cutaneous response that has been observed in patients with either hematologic malignancies or solid tumors. An illustrative case of acral erythema in a woman with acute myelogenous leukemia is reported. The patient initially presented in blast crisis with concurrent cutaneous lesions of Sweet's syndrome. She subsequently showed acral erythema after being treated with cytosine arabinoside and idarubicin (an analogue of doxorubicin). The pathogenesis and treatment of acral erythema are reviewed. PMID- 8444049 TI - A case of Buerger's disease. AB - Buerger's disease (thromboangiitis obliterans) is an uncommon vascular occlusive disease most commonly affecting the lower extremities of young male tobacco smokers. We report the case of a thirty-five-year-old man who presented with nonhealing ulcerations of several toes. Arteriography revealed severe bilateral vascular occlusion. The patient failed to respond to intensive topical care, nifedipine, pentoxifylline, hyperbaric oxygen, intravenous antibiotics, and whirlpool. He continued to smoke, and eventually became septic, requiring amputations of his gangrenous left second toe and right leg below the knee. PMID- 8444050 TI - Treatment of gold salt-induced oral lichen planus: report of a case. AB - A case of gold salt-induced oral lichen planus is reported. The oral lesions were successfully managed with a topical corticosteroid rinse. Gold salts, oral symptoms, and the use of the systemic inducing agent/immunosuppressant in combination with a topical corticosteroid are reviewed. PMID- 8444051 TI - Preliminary experience with a flashlamp-pulsed tunable dye laser for treatment of benign pigmented lesions. AB - The principle of selective photothermolysis has been extended from the treatment of vascular to benign pigmented lesions. Cafe au lait birthmarks, solar lentigines, and ephelides can now be removed with a new pulsed-dye laser, with a low risk of scarring or hypopigmentation. PMID- 8444052 TI - Atopic dermatitis associated with dermatophyte infection and Trichophyton hypersensitivity. AB - An atopic patient with tinea unguium, immediate hypersensitivity to Trichophyton, and elevated specific IgE antibody to Trichophyton had recalcitrant hand and foot eczema that resolved following the administration of systemic antifungal therapy for her tinea unguium. The patient fulfills criteria for the atopic-chronic dermatophytosis syndrome described by Jones. The authors suggest that the patient's atopic dermatitis may have been exacerbated by her chronic dermatophyte infection and Trichophyton hypersensitivity. PMID- 8444053 TI - Nevus of Ota acquisita of late onset. AB - Nevus of Ota is a melanotic pigmentary disorder characterized by its distinctive cutaneous distribution involving skin innervated by the trigeminal nerve. Most cases are clinically manifest at birth or around puberty; however, acquired lesions in adults have been reported. We report a case of nevus of Ota acquisita that occurred in an eighty-one-year-old man. PMID- 8444054 TI - Bilateral accessory tragus. AB - Bilateral accessory tragus is a rare congenital malformation of the external ear. An isolated, nonfamilial occurrence of bilateral accessory tragus in a forty three-year-old man is presented, and the literature is reviewed. Congenital firm, preauricular papules should be recognized as accessory tragi. PMID- 8444055 TI - Open-label study of the safety and efficacy of naftifine hydrochloride 1 percent gel in patients with distal subungual onychomycosis of the fingers. AB - Optimal topical therapy for distal subungual onychomycosis is not available. An open-label study was performed to determine the safety and efficacy of naftifine hydrochloride (Naftin) 1 percent gel in patients with this disorder of the fingers. Ten patients with culture-proven distal subungual onychomycosis were treated twice daily for six months with naftifine hydrochloride 1 percent gel. At monthly intervals, the target nail was trimmed, the nail bed debrided, and global clinical assessment recorded. Following months three, six, and eight (two months after treatment), the target nail underwent evaluation with potassium hydroxide wet mount and fungal culture. After six months of therapy, eight of ten patients showed negative results of fungal culture and eight of ten patients showed clinical improvement. Adverse effects were minimal and included mild peeling in two patients and mild fissuring with transient fingertip numbness in one patient. PMID- 8444056 TI - Pharmacokinetics and cerebrospinal fluid concentrations of cefixime in infants and young children. AB - Limited data are available about cefixime pharmacokinetics and cerebrospinal fluid (CSF) penetration in infants and young children. Ten patients with bacterial meningitis and 8 undergoing CSF shunt placement, aged 2-22 months (mean 9.5 +/- 6.5 months), were given a single dose of cefixime suspension, 8 mg/kg, before undergoing a routine lumbar puncture. Patients were fasted for 2 h before and 2 h after drug administration. Blood samples were collected just before drug administration (0 h) and at 1, 2, 3, 4, 6, 8 h; CSF was obtained at 1-8.8 h after drug administration. Cefixime was measured by a high-performance liquid chromatographic method. The peak serum concentration of cefixime ranged from 0.85 to 6.2 (mean 3.1) micrograms/ml and occurred at 2-8 h (mean 4.5). The area under the serum concentration-time curve ranged from 5.3 to 28.4 micrograms h/ml, and the elimination half-life ranged from 2.6 to 5.6 h. CSF concentrations ranged from 0.02 to 0.57 micrograms/ml. The mean CSF concentration of cefixime was 0.22 micrograms/ml in patients with meningitis and 0.10 microgram/ml in those undergoing shunt placement (p < 0.02). The mean CSF concentration/serum concentration ratio was 11.7 in patients with meningitis compared with 5.4 in those undergoing shunt procedures (p < 0.02). These data indicate that cefixime can be considered as an alternative to other antimicrobials for infants and children with respiratory and urinary tract infections, since the observed peak serum concentration exceeded the minimum inhibitory concentrations of the common pathogens by severalfold.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444057 TI - Survey of antimicrobial resistance to oral antibiotics in Italy. AB - The susceptibility of approximately 4,200 fresh clinical isolates to eleven different orally available compounds was assessed in ten Italian microbiology institutions during summer 1991. A standardized microdilution system including all the material necessary was employed to assess the antibacterial activity of ampicillin, ampicillin plus sulbactam, amoxicillin plus clavulanic acid, cefadroxil, cephalexin, cefaclor, cefuroxime, cefetamet, doxycycline, erythromycin, and clindamycin. The amino-penicillins (including the beta lactamase inhibitor combinations) were highly active against the streptococci, whereas cefetamet was the most active compound against Enterobacteriaceae, exhibiting good activity against the streptococci as well. The analysis of distribution of susceptibility revealed that there is a good discrimination between susceptible and resistant strains for cefetamet in any case, whereas the discrimination is low for the aminopenicillin/inhibitor combinations and the older cephalosporins in at least some of the gram-negative species. PMID- 8444058 TI - Contributions of post-antibiotic lag and repair-recovery to the post-antibiotic effects of ciprofloxacin on Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Streptococcus pyogenes. AB - A viable counting technique was used to determine the post-antibiotic effect (PAE) of ciprofloxacin against four bacterial species, treated with either one or four times the minimum inhibitory concentration for 1 or 3 h. PAE were demonstrated with Escherichia coli, Staphylococcus aureus or Streptococcus pyogenes after exposure to either concentration for both times. No clear PAE was demonstrated for Klebsiella pneumoniae after any treatment. In some cases, PAE was due to an increased post-treatment lag phase, which was followed by nearly normal multiplication, whereas in other cases a long lag was followed by abnormally rapid cell division, with the generation times of treated cultures being much less than those of the corresponding drug-free controls. This is evidence of recovery of cells that have completed DNA repair. S. aureus, E. coli and K. pneumoniae all exhibited evidence of this type of repair even though K. pneumoniae gave no significant PAE. However, the post-treatment generation times of S. pyogenes, which produced the greatest PAE, gave no evidence of such repair. It is concluded that PAEs may result from a variety of factors. PMID- 8444059 TI - Antimicrobial effects of the tetrachlorodecaoxygen-anion complex on oropharyngeal bacterial flora: an in vitro study. AB - The susceptibility of 276 different strains of bacteria derived from the oropharyngeal flora to the tetrachlorodecaoxygen-anion complex (TCDO) was tested using the agar dilution method. The results showed that at therapeutic concentrations of the drug the growth of all the strains tested was inhibited, with the exception of Candida albicans. The pathogenic anaerobes proved to be particularly sensitive to TCDO. PMID- 8444060 TI - Bioactivity of flurithromycin and other macrolides against intracellular susceptible staphylococci. AB - The intracellular activity of flurithromycin, erythromycin, roxithromycin and miocamycin against susceptible clinical isolates of Staphylococcus aureus, phagocytosed by human monocytes, was investigated. Intracellular bioactivity was studied in a 24-hour assay, using experimental conditions which allowed the intracellular growth of bacteria. A colony counting method was used to differentiate between intracellular bacteriostatic and bactericidal activity of antibiotics. Moreover, the effect of macrolides against extracellular staphylococci was assessed. All agents showed higher intracellular than extracellular activity against staphylococci. At low concentration (0.1 mg/l) they had intracellular bacteriostatic activity. At concentrations higher than the minimal inhibitory ones (1 and 5 mg/l), miocamycin only still produced a bacteriostatic effect while flurithromycin, erythromycin and roxithromycin also showed intracellular bactericidal activity. PMID- 8444061 TI - Antistaphylococcal and antienterococcal activity of the new teicoplanin amide derivative MDL 62873. AB - In vitro response of 469 clinical isolates of gram-positive cocci was tested against MDL 62873 by the agar dilution method. The bacteria consisted of 407 isolates of staphylococci and 62 strains of enterococci. In vitro activity of MDL 62873 was compared with that of ampicillin, augmentin, erythromycin and vancomycin. All the isolates were completely inhibited by MDL 62873 at an MIC ranging between 0.25 and 8.0 micrograms/ml. In vitro activity of this new amide derivative of teicoplanin was far superior to that of ampicillin, augmentin and erythromycin and equal to or slightly better than that of vancomycin. PMID- 8444062 TI - Antitumor effect of a mycotoxin: rubratoxin B. AB - The antitumor effect of rubratoxin B, a mycotoxin, has been studied. Yoshida ascites sarcoma cells, in vitro in contact for 30 min with the drug and injected immediately afterwards into young rats by the intraperitoneal route, produced the survival of 80% of the animals and the doubling of the median survival time of the rats developing neoplasia. In vivo administration of the drug by the intraperitoneal route 24 h after implantation of tumor cells determined the prolongation of median survival time; supplied by other routes both against T8 sarcoma of Guerin and Yoshida ascites sarcoma it was ineffective. The differences between in vitro and in vivo results can be explained by a rapid neutralization of the drug on behalf of the organism's enzymes or by being bound to proteins and peritoneal cells unlike tumor cells. PMID- 8444063 TI - Pharmacokinetics of fluconazole in normal volunteers. AB - The pharmacokinetic profile of fluconazole, after 100 mg i.v. infusion or oral administration of a single 50 mg or 150 mg dose, was investigated in 18 healthy volunteers. At a dose of 100 mg i.v., the half-life (t1/2 beta) was 29.73 +/- 8.05h. The mean residence time in the plasma was 27.56 +/- 5.98 h. The post distributive volume V beta = 52.16 +/- 9.83 l, approximating that of total body water. Renal excretion accounted for 61.64 +/- 8.80% of the drug elimination after 48 h, with renal clearance Clr = 12.91 +/- 2.83 ml/min. Plasma clearance (Clp) was 21.03 +/- 5.07 ml/min. At oral doses of 50 and 150 mg the distribution and elimination of fluconazole resembled that following i.v. infusion. The peak levels in plasma at 2.5 h were 0.93 +/- 0.13 and 2.69 +/- 0.43 micrograms/ml, respectively. The large distribution volume, the long half-life and mean residence times, combined with a rapid absorption after oral administration, suggest that fluconazole will be effective at a wide range of body sites. PMID- 8444064 TI - Inhibition of DNA synthesis in different tissues of L1210-leukemia-bearing mice by new platinum (II) complexes. AB - The inhibition of [14C]thymidine incorporation into DNA of tumor and normal tissues of L1210-leukemia-bearing mice by single doses of cis diamminedichloroplatinum (II) (cisplatin, cis-DDP) and two newly synthesized platinum (II) complexes containing as ligands dimethyl aminomethylphosphine oxide (complex I) and methyl bis(aminomethyl)phosphine oxide (complex II) was studied and used as an indication of drug toxicity. All three complexes caused selective inhibition of precursor incorporation in L1210 cells as compared to host tissue cells. cis-DDP caused a complete block of incorporated thymidine in tumor cells during more than 48 h, whereas in intestinal mucosa and bone marrow reverse inhibition was observed. In spleen, liver and kidney the inhibition was about 50% and endured up to 96 h without reversal. Complex I treatment of L1210 cells resulted in an earlier recovery of thymidine incorporation into DNA in comparison with cis-DDP. Towards all other normal tissues compound I was less toxic than cis DDP. Unlike cis-DDP and complex I, complex II was less active against L1210 cells and most toxic against bone marrow and kidney. PMID- 8444065 TI - State actions to control fetal abuse: ramifications for child welfare practice. AB - The growing concern over the plight of infants born addicted to alcohol or other drugs has moved some legislatures and courts to develop punitive responses. Statutes and case law have evolved in both the civil and criminal arenas. Under civil law, the parens patriae power of the state has been invoked to remove children from the custody of their mothers at birth. Under criminal law, a variety of approaches have been used to punish the mother for her actions while pregnant. This article reviews recent case law and surveys state statutes to illustrate strategies currently being employed, and suggests ramifications for child welfare practice. PMID- 8444066 TI - Role of villous surface area in absorption. Science versus religion. PMID- 8444067 TI - Contraction of collagen gels by intestinal epithelial cells depends on microfilament function. AB - We have developed a model system to quantify the tractional forces generated by intestinal epithelial cells during organization into a confluent epithelial cell sheet. In this model system, IEC-6 cells, a rat intestinal crypt cell line, rapidly contracted collagen gels reducing the gel surface area by 97% at 24 hr. The tractional forces measured by gel contraction were directly related to the number of cells added and were inversely related to the collagen concentration of the gel. Actin microfilament function was required for gel contraction, but microtubular function was not. Fetal bovine serum and protein synthesis were required for maximal gel contraction. IEC-6 (5 x 10(5)) cells per gel and fibroblasts (5 x 10(4)) cells added to collagen gels resulted in contraction of the gels by 50% at 24 hr. Therefore, intestinal epithelial cells and fibroblasts generate tractional forces of similar strength capable of organizing the surrounding extracellular matrix, which should be considered in models of intestinal morphogenesis and repair. PMID- 8444068 TI - Mediation of anaphylaxis-induced jejunal circular smooth muscle contraction in rats. AB - Altered intestinal motility and diarrhea are features of food protein-induced intestinal anaphylaxis in the conscious rat. These experiments were performed to determine the mediator(s) responsible for jejunal circular smooth muscle contraction during this response. Hooded-Lister rats were sensitized by intraperitoneal injection of 10-micrograms egg albumin, and controls were sham sensitized with saline. Fourteen days later the contractility of the circular muscle in jejunal segments (mucosa intact) was examined in standard tissue baths in response to antigen (Ag) or other agents. While control and sensitized tissues contracted in similar fashion in response to stretch, bethanechol, histamine, or 5-hydroxytryptamine (5HT), Ag contracted only the segments of sensitized animals. The contractile response was: (1) specific to the sensitizing Ag, as bovine serum albumin did not induce contraction and (2) could be passively transferred with serum containing specific immunoglobulin E antibody (IgE-Ab). Concanavalin A, which degranulates both mucosal and connective tissue-type mast cells, and compound 48/80, which degranulates only connective tissue-type mast cells produced contractile responses. Ag-induced contraction was significantly inhibited by the mucosal and connective tissue-type mast cell stabilizer doxantrazole, but not the connective tissue mast cell stabilizer disodium cromoglycate. Diphenhydramine and cimetidine together significantly inhibited histamine-induced contraction, but failed to effect the Ag-induced contraction in sensitized tissues. While the contractile response to 5HT was reduced in the presence of methysergide (5HT1-receptor antagonist), cinanserin (5HT2-receptor antagonist), and ICS 205-930 (5HT3-receptor antagonist), only cinanserin significantly inhibited the contractile response to Ag. Indomethacin significantly inhibited Ag-induced contraction. Ag-induced contraction was resistant to atropine and tetrodotoxin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444069 TI - Duodenal brush-border mucosal glucose transport and enzyme activities in aging man and effect of bacterial contamination of the small intestine. AB - Duodenal biopsies were collected from 38 subjects (24 female and 14 male) ranging in age from 55 to 91 years. Evidence of bacterial contamination of the small bowel (BCSB) was sought at the same time by bacterial culture of duodenal aspirates and by hydrogen and [14C]glycocholic acid breath tests; subjects were considered to be positive for BCSB if any one of the three tests was abnormal. Biopsies were analyzed for six brush-border membrane enzyme activities: maltase, sucrase, lactase, alkaline phosphatase, leucine aminopeptidase, and alpha glucosidase. Analysis of covariance with age as the covariate indicated no significant effect of age on the specific activities of these enzymes. Mucosal Na(+)-dependent glucose transport was quantified in brush-border membrane vesicles prepared from the biopsies. In all groups, glucose transport at 20-30 sec was greater (ranging from mean values of 2.45 to 3.66 times) than at 45 min, consistent with Na(+)-coupled glucose transport, and no significant effect of age was observed. BCSB had no significant effect on specific activities of any of the duodenal mucosal hydrolases but was associated with reduced (P = 0.05) brush border glucose transport. None of the variables studied was significantly affected by the gender of subjects. In conclusion, these biochemical data do not support the contention that reduced capacity for carbohydrate absorption in the elderly is explained by reductions in duodenal brush-border mucosal disaccharidase activities or glucose transport. PMID- 8444071 TI - Anti-endothelial cell antibodies in inflammatory bowel disease. AB - Antibodies to endothelial cells may be involved in the pathogenesis of vasculitic disorders. In view of recent evidence implicating intestinal vascular injury in the pathogenesis of inflammatory bowel disease, we have sought anti-endothelial cell antibodies in affected patients, examined their relationship to vascular injury, and tested their ability to mediate endothelial cell cytotoxicity in vitro. Anti-endothelial cell antibody levels were elevated in ulcerative colitis (P < 0.0001) and Crohn's disease (P < 0.05) compared with healthy controls. In ulcerative colitis, anti-endothelial cell antibody levels were related to disease activity and correlated with circulating levels of von Willebrand factor (r = 0.58, P < 0.01), a marker of vascular injury. Anti-endothelial cell antibodies, however, were not directly cytotoxic to endothelial cells in vitro. These data indicate, for the first time, an association between anti-endothelial cell antibody levels and vascular injury in vivo and suggest that they may be important in the pathogenesis of inflammatory bowel disease, particularly ulcerative colitis. PMID- 8444070 TI - Effects of metronidazole and misoprostol on indomethacin-induced changes in intestinal permeability. AB - In previous open studies, misoprostol and metronidazole reduced nonsteroidal anti inflammatory drug-induced intestinal permeability changes and inflammation respectively. We assessed the effects of indomethacin treatment (50 mg three times a day) for one week with either coadministered metronidazole (400 mg twice a day, group 1, N = 9) or misoprostol (200 micrograms four times a day, group 2, N = 7) on intestinal permeability to [51Cr]EDTA and mannitol in healthy volunteers, using double-blind, placebo-controlled, randomized techniques. Given alone, neither metronidazole nor misoprostol affected [51Cr]EDTA permeation, whereas indomethacin alone increased it from 1.20 (0.40) [mean percent urinary recovery (SD) groups 1 and 2] to 2.43 (0.72), P < 0.002. Coadministered metronidazole (group 1) prevented this increase [1.10 (0.39) before, 1.55 (0.54) after, P > 0.05], whereas misoprostol (group 2) did not [1.31 (0.51) before, 3.26 (1.10) after, P = 0.005]. No drug regimen altered mannitol permeation. Indomethacin and misoprostol did not affect urinary recovery of intravenously administered probes. The results with metronidazole, if related to its antibacterial effects, support evidence from animal models that bacteria contribute to NSAID-induced intestinal damage. The previously reported reduction of indomethacin-induced increased permeability by misoprostol during a one-day study is not seen when the drugs are used in standard clinical doses for one week. PMID- 8444072 TI - Comparison of scintigraphy with indium-111 leukocyte scan and ultrasonography in assessment of X-ray-demonstrated lesions of Crohn's disease. AB - The aim of this study was to compare the results obtained with an indium-111 scan with those obtained with less expensive and harmless ultrasonography to evaluate the location and inflammatory activity of Crohn's disease. Thirty-one patients previously studied with x-ray underwent abdominal 111In scans and ultrasonography (US). Sensitivity and specificity of US in detecting lesions seen with 111In scan were 77% and 92.8%, respectively. Sensitivity and specificity of 111In scan in detecting x-ray-defined lesions were 69.2% and 92.7%; the figures for US were 73% and 93.3%, respectively. Considering the evaluation of disease activity, ultrasonographic bowel wall thickness was significantly related to scintigraphic intensity of emission (r = 0.75 P < 0.01). Our experience suggests that US provided information about the location and inflammatory activity of lesions similar to that obtained from 111In scan. PMID- 8444073 TI - Midgut volvulus as a complication of intestinal malrotation in adults. AB - Seven adults with midgut volvulus as a complication of malrotation are presented. All patients were men with an average age of 33 years. Four presented with long histories of intermittent abdominal pain. In three patients, the twisted, corkscrew appearance of the barium column in the duodenum and proximal jejunum in an upper gastrointestinal series made the diagnosis. In the remaining patient, small-bowel follow-through performed three years before surgery showed intestinal malrotation. Three patients presented with the acute onset of severe abdominal pain. Plain films showed small-bowel obstruction and pneumatosis intestinalis in two patients and only nearly complete small-bowel obstruction in the third. Barium studies were not done in this group because of the need to proceed to exploratory laparotomy and the risk of perforation. In one patient, abdominal angiography suggested the diagnosis by showing abnormal courses of the mesenteric vessels to the volvulized segment of small bowel. All three of these patients showed ischemic segments of bowel at laparotomy. PMID- 8444074 TI - Relationship between methane production and breath hydrogen excretion in lactose malabsorbing individuals. AB - Recent studies have shown reduced breath hydrogen (H2) excretion in methane (CH4) producing healthy individuals following ingestion of lactulose. This questions the reliability of the breath hydrogen test (BHT) in CH4 excretors, but the relationship between CH4 and H2 excretion in other clinical applications of the BHT is not known. We reviewed BHT results in two groups of subjects: (1) 385 children tested for lactose malabsorption in a hospital setting, and (2) 109 lactose-malabsorbing patients tested with a home kit. The percentage of lactose malabsorbers in group 1 (51%) was the same regardless of CH4-producing status (P = 0.97). The BHT data from group 2 showed a positive correlation (r = 0.6, P < 0.000001) between the magnitude of the rise in CH4 and H2 concentrations, and the H2 excretion curves were significantly higher in the CH4-producing individuals. We conclude that attention to CH4-producing status is not necessary in the interpretation of the lactose BHT. PMID- 8444075 TI - Types, causes, and therapies of hepatitis occurring in liver transplant recipients. AB - Liver transplantation (OLTx) has become a common life-saving procedure for individuals with chronic advanced liver disease. It is also used in the clinical treatment of patients with fulminant hepatic failure and those with primary neoplastic disease of the liver. Despite its overall success in restoring meaningful life to those who undergo the procedure, the posttransplant life of a liver allograft recipient is not without hazard. A common problem following liver transplantation is the finding of abnormal liver injury tests reflecting a "hepatitis" that can not be ascribed to allograft rejection. The majority of such cases are a consequence of either a technically flawed operation, drug-induced liver injury, or one or another form of viral hepatitis. Each of these problems is discussed in the following clinical review. PMID- 8444076 TI - Hepatitis viral markers in patients undergoing primary liver transplants. AB - The purpose of the study was to determine the prevalence in liver transplant (OLTx) patients of the hepatitis markers (anti-A, anti-B, anti-C, anti-D and HBsAg) and the interrelationships between markers and patients' sexes, ages, dates of transplant, clinicopathological diagnoses, and short-term survivals. Slightly more than half of the patients were male. Anti-A and anti-B were about evenly distributed between male and female. Anti-C, anti-D, and HBsAg were far more common in males. Age and year of transplant showed only a moderate increase in anti-A with increasing age. Anti-A was found in 57% of all patients, anti-B in 18%, anti-C in 17%, and HBsAg in 17%. Anti-D was tested only in patients who were positive for anti-B or HBsAg and occurred in 21 (11%) of 185. The poorest short term survival occurred in males who showed both anti-A and HBsAg. PMID- 8444077 TI - Human sphincter of Oddi motility and cholecystokinin response following liver transplantation. AB - The reported incidence of sphincter of Oddi dysfunction following orthotopic liver transplantation has ranged from 3% to 7%. If sphincteric dysfunction is unrecognized, therapy may be inappropriate; when recognized, extensive surgery may be required. To prospectively identify patients with sphincteric dysfunction, we performed sphincter of Oddi motility studies through the t-tube tract three months after transplantation. Baseline sphincter motility and response to intravenous cholecystokinin were evaluated. The results of 10 subjects are reported; nine had normal basal sphincter pressure (16 +/- 5.8 mm Hg), and all had normal frequency (3.6 +/- 1/min), amplitude (86 +/- 31 mm Hg), and duration (4.5 +/- 1 sec) of phasic contractions. One subject had an elevated basal pressure (47 mm Hg). All, including the subject with elevated basal pressure, demonstrated a normal response to intravenous cholecystokinin with significant inhibition of phasic contraction frequency and amplitude. We demonstrate that simultaneous studies of the sphincter and duodenum can be obtained via the t-tube tract, providing the opportunity for prospective evaluation of sphincteric function. We conclude that sphincter of Oddi function usually remains normal following liver transplantation with choledochocholedochostomy. PMID- 8444078 TI - Development of reliable artificial liver support (ALS)--plasma exchange in combination with hemodiafiltration using high-performance membranes. AB - A new artificial liver support system (ALSS) consisting of plasma exchange (PE) in combination with hemodiafiltration (HDF) using high-performance membranes of polymethyl methacrylate (PMMA) and cellulose triacetate (CTA) was developed to efficiently remove middle molecules from plasma and treat fulminant hepatic failure (FHF) complicated by the onset of hepatic coma. Twenty-seven patients with FHF due to viral hepatitis, two with type A (HA), nine with type B (HB), and 16 with type non-A, non-B (NANB) underwent therapy with this new ALSS over the last five years. Three patients with an exacerbation of chronic HB and 15/16 with type NANB hepatitis were treated with interferon (IFN) also. Of these, 25 patients (92.6%) regained consciousness and 15 (55.6%) [1/2 (50%) with type A, 6/9 (66.7%) with type B and 8/16 (50%) with type NANB hepatitis] survived. Including four patients who survived with intensive care and plasma exchange alone, 19/31 (61.3%) patients survived. Because of its biocompatibility, both survivors and nonsurvivors could be sustained with the ALSS without complications for long periods (19.3 days for the survivors and 32.4 days for nonsurvivors). With this ALSS the ability to sustain life for such prolonged periods allows hepatic regeneration to occur and result in patient survival. It is anticipated that this new ALSS will not only be of value in cases of fulminant hepatic failure but that it may also play a role in sustaining life for those awaiting liver transplantation. PMID- 8444079 TI - Reduced production of immunoreactive interleukin-1 by peripheral blood monocytes of patients with acute and chronic viral hepatitis. AB - The in vitro production of interleukin-1 beta by peripheral blood monocytes derived from patients with various liver diseases was studied. An impaired production of immunoreactive interleukin-1 (IL-1) (mean +/- SEM) by monocytes stimulated with an optimal dose (100 ng/ml) of lipopolysaccharide was observed in patients with chronic hepatitis B (N = 13; 32 +/- 6 pg/ml) or chronic hepatitis C (N = 13; 61 +/- 12 pg/ml) as compared to those of healthy control individuals (N = 35; 166 +/- 24 pg/ml; P = 0.0003 and P = 0.015, respectively), whereas an unaltered IL-1 production was seen in patients with alcoholic cirrhosis (N = 23; 125 +/- 28 pg/ml) and primary biliary cirrhosis (N = 6; 111 +/- 33 pg/ml). Similar to the situation seen in chronic viral hepatitis, lipopolysaccharide stimulated monocytes from patients with acute hepatitis also showed a decreased IL-1 production in the first week after onset of jaundice (N = 17; 55 +/- 20 pg/ml; P = 0.001) and a return to normal in the second and third week. An impaired production of IL-1 in chronic as well as acute viral hepatitis is a further example of the known disturbed immunoregulation in this disease. PMID- 8444080 TI - Gallbladder dynamics in chronic pancreatitis. Relationship to exocrine pancreatic function, CCK, and PP release. AB - Gallbladder dynamics, cholecystokinin (CCK), and pancreatic polypeptide (PP) release were studied in 14 patients with chronic pancreatitis (CP) (2 females, 12 males; age range 24-56 years) and 12 control subjects (4 females, 8 males, 21-50 years). On day 1, gallbladder contractility was investigated after ceruletide intravenous infusion (2.5 ng/kg/min for 10 min). On day 2, a mixed standard test meal (1450 kJ) was administered orally. Gallbladder volume was assessed at three time intervals before (-30, -15, 0 min) and at 5, 10, 20, 30, 40, 50, 60, 80, 100 and 120 min after stimulation by means of ultrasonography. CCK and PP plasma levels were determined at each time interval. Exocrine pancreatic function was assessed using the pancreolauryl serum test (PLT). Six patients with CP had severe exocrine pancreatic insufficiency (EPI) (PLT < 1.8 micrograms/ml) with steatorrhea, eight patients had mild-moderate EPI. Fasting gallbladder volume was increased in CP (32.3 +/- 3.1 cm3) as compared to controls (20.5 +/- 1.2 cm3) (P < 0.01). Peak gallbladder contraction (percent of initial volume) in CP ranged from 5 to 55% (controls: 8-46%) following ceruletide and from 17 to 86% (controls: 27-80%) following the test meal (NS). There was no correlation between the degree of EPI according to PLT and peak gallbladder contraction. Gallbladder emptying in CP patients was not different from controls, although the postprandial CCK response was significantly impaired (P < 0.01). Postprandial PP response in CP was correlated with the PLT result (r = 0.78; P < 0.01) but not with gallbladder emptying or refilling time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444081 TI - Gallbladder dysfunction in diabetes mellitus. AB - To further elucidate the mechanism of impaired gallbladder emptying in diabetics with and without neuropathy, gallbladder function was assessed by ultrasonography following a medium-chain triglyceride (lipomul, 1.5 mg/kg) infusion into the duodenum and compared to that during intravenous infusion of cholecystokinin in diabetic women. Results were compared with five healthy control women. Mean (+/- SD) maximal percent gallbladder volume in diabetics following lipomul was reduced to 49 +/- 8% and after intravenous cholecystokinin to 47 +/- 9%, which was less than those in controls, 21 +/- 9% and 24 +/- 6%, respectively, but not significantly different. Further analysis of gallbladder emptying to lipomul differentiated two subgroups of diabetics: one subgroup (N = 5) had emptying comparable to controls (responders), while the other (N = 5) had very modest emptying (nonresponders). Two of the patients in the latter group had normal gallbladder emptying during exogenous cholecystokinin and their response would be compatible with visceral neuropathy. Blood levels of cholecystokinin, measured by bioassay, following lipomul and exogenous cholecystokinin were similar in controls and diabetics. Presence of diabetic neuropathy did not correlate with impaired gallbladder emptying. Follow up at 6 and 12 months of the three nonresponder diabetics revealed that no gallstones had developed and that two of them became responders to exogenous cholecystokinin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444082 TI - Diabetes in chronic alcoholic pancreatitis. Role of residual beta cell function and insulin resistance. AB - Chronic alcoholic pancreatitis (CAP) is often complicated by the onset of diabetes mellitus. The aim of this study was to assess the residual beta cell function (evaluated by means of the glucagon test) and the mean disposal rate of insulin (with the insulin tolerance test) in 66 CAP patients with or without abnormalities of glucose metabolism and in 19 control subjects. On the basis of our data, we conclude that the glucose metabolism abnormalities in chronic pancreatitis occurs as a result not merely of impaired production of endogenous insulin, but also as result of a combination of the latter together with insulin resistance. PMID- 8444083 TI - Simultaneous determinations of pancreatic phospholipase A2 and prophospholipase A2 in various pancreatic diseases. AB - Pancreatic phospholipase A2 (PLA2) is secreted into the pancreatic juice by pancreatic acinar cells as a proenzyme (proPLA2), which is activated by trypsin. Radioimmunoassays with monoclonal antibodies to PLA2 and proPLA2 were used to examine the serum PLA2 and proPLA2 levels simultaneously in patients with various pancreatic diseases. In healthy subjects, proPLA2 proved to be the major form of the enzyme. The serum PLA2 level were found to be significantly increased in patients with acute pancreatitis, the active phase of chronic relapsing pancreatitis, and the early stage of pancreatic cancer. In the terminal stage of pancreatic cancer the serum PLA2 level became low. In patients with chronic pancreatitis, significant correlations were observed between the levels of factors evaluated by the secretin test and the serum total PLA2 and proPLA2 level, but not the PLA2 level. The serum PLA2 and proPLA2 concentrations, and the proportion of proPLA2 in the total, were within normal ranges in patients with liver cirrhosis, hepatocellular carcinoma, and chronic renal failure. These results suggest that simultaneous measurements of serum PLA2 and proPLA2 are clinically useful for diagnosis and monitoring of the active phase of pancreatitis. PMID- 8444084 TI - Role of bile acids and metabolic activity of colonic bacteria in increased risk of colon cancer after cholecystectomy. AB - Since the metabolic activity of the colonic flora plays a definite role in colon cancer and an increased incidence of this disease is reported after cholecystectomy, we studied the metabolic activity of the colonic flora in a group of postcholecystectomy patients and matched controls by measuring, as representative end products of the bacterial metabolism, their fecal bile acids (BA), fecal 3-methylindole (SK) and indole (IN), and respiratory methane and hydrogen. Patients had significantly higher SK and lower IN, and, among BA, higher lithocholic (LCA) and chenodeoxycholic acid concentrations and LCA/deoxycholic acid ratio in the stools than controls. Similar differences from controls were reported for colon cancer. Comparable bacterial metabolic activities are thus operative in the large bowel of postcholecystectomized and colon cancer patients. This supports the biological plausibility of the association of cholecystectomy and colon cancer. PMID- 8444085 TI - Effects of gastrin and difluoromethylornithine on growth of human colon cancer. AB - The effect of difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase activity, was evaluated in vivo and in vitro on the growth of a gastrin-sensitive human colon carcinoma (WiDr). In vivo, mice bearing the tumor treated with pentagastrin had larger tumors with higher ornithine decarboxylase activity and polyamine content (P < 0.05) than mice not treated with pentagastrin. Difluoromethylornithine treatment significantly decreased ornithine decarboxylase in both the pentagastrin-treated and the untreated animals; however, DFMO had no effect on tumor volume, weight, protein, or DNA content. In cell culture, gastrin treatment increased WiDr cell number and [3H]thymidine incorporation in the presence or absence of serum. In serum-free conditions, however, gastrin stimulated cell growth without concomitantly increasing ODC activity. DFMO, on the other hand, decreased both ODC activity and growth. These studies suggest that the trophic effect of gastrin on WiDr human colon cancer is independent of ODC activity. Since gastrin treatment increased ODC activity in vivo, gastrin may interact in vitro with other factors present in serum that can alter ODC activity. PMID- 8444086 TI - Mortality in patients with ulcerative colitis in Leicestershire, 1972-1989. An epidemiological study. AB - The mortality in 1014 patients with ulcerative proctocolitis diagnosed while resident in Leicestershire identified in a population-based study from 1972 to 1989 was assessed. Ninety-two Europeans and one South Asian died. The standardized mortality ratio (SMR) in South Asians was 26 (95% confidence interval 0-147). In Europeans the overall mortality was not increased, the SMR was 93 (95% confidence interval 75-114). The SMR did not differ between established disease extents, but was highest in those patients in whom the extent was undefined (SMR = 237, 95% confidence interval 130-397). Comparison of SMRs and survival curves showed no difference in mortality in patients diagnosed from 1972 to 1980 and from 1981 to 1989. Mortality was similar in patients who had colectomy and those who had not (SMR = 130, 95% confidence interval 71-219, chi 2(1) = 1.2, NS). Mortality did not change during the study. These findings should be made available to patients and their families. PMID- 8444087 TI - Colonic mucosal pH in humans. AB - Mucosal pH was measured at specific anatomic segments within the colon using a flexible pH probe in patients prepared for colonoscopy. The data revealed similar pH measurements along the length of the colon, irrespective of the presence or absence of colorectal neoplasia. Patients exhibited a relatively acidic right colon; a more alkaline transverse, left, and sigmoid colon; and a relatively acidic rectum. There were no apparent gender- or age-related effects on colonic mucosal pH. PMID- 8444089 TI - Invagination of vermiform appendix. PMID- 8444090 TI - Efficacy of famotidine for omeprazole-refractory gastric ulcer. PMID- 8444088 TI - Effect of cisapride on relapse of esophagitis. A multinational, placebo controlled trial in patients healed with an antisecretory drug. The Italian Eurocis Trialists. AB - The effect of a prokinetic agent, cisapride, on the relapse of reflux esophagitis was investigated in a randomized, double-blind trial conducted in 443 patients whose esophagitis had previously been healed with an acid antisecretory drug. Patients received cisapride, 20 mg at night, cisapride 10 mg twice daily, or placebo for 12 months or until endoscopic relapse was confirmed endoscopically. In 88% of all patients (respectively 133, 132, and 124), endoscopic data were available at discontinuation of treatment. In comparison with placebo, the two cisapride regimens prolonged both the time to endoscopically confirmed relapse (Kaplan-Meier analysis; P = 0.001) and the time to symptomatic relapse (P = 0.012). The life-table endoscopic relapse rates at 12 months were 51% for placebo, 32% for cisapride 20 mg at night (P = 0.005), and 34% for cisapride 10 mg twice daily (P = 0.02). Patients with more severe esophagitis before healing relapsed more rapidly during maintenance therapy, regardless of the treatment regimen. Adverse events were infrequent in all three groups. These findings indicate that maintenance treatment with the prokinetic drug cisapride prevents the relapse of esophagitis after it has been healed by acid antisecretory therapy. PMID- 8444091 TI - [Nursing students in the department for depressives. Organization and control of the results of practical teaching]. PMID- 8444092 TI - [Special wards for depressive patients]. PMID- 8444093 TI - [Nursing in a depression unit. Fears--expectations--developments]. PMID- 8444094 TI - [Nursing in a depression unit. Work in unit 1B in the Northern Black Forest district hospital]. PMID- 8444095 TI - [Possibilities and limits of the team identity in a depression unit]. PMID- 8444096 TI - [The importance of guilt experiences in depressive people]. PMID- 8444097 TI - [Depressions in children and adolescents]. PMID- 8444098 TI - [Model of a documentation system. Logical in its set-up, nursing oriented, clearly arranged for all professionals, without the need of much writing, therefore not only for the initiated]. PMID- 8444099 TI - [Between suicide and a new kidney. Psychological and physical problems of patients needing chronic hemodialysis]. PMID- 8444100 TI - [Effect of the start of the morning shift at 6:00 a.m. on nurses and patients. Description of research and results]. PMID- 8444101 TI - [Symptoms of depressive disease]. PMID- 8444102 TI - [Halofantrine in the treatment of imported malaria in nonimmune travelers]. AB - The efficacy (criteria: cure rate, time to resolution of fever or absence of parasites) and safety (criteria: clinical side effects, altered laboratory parameters) of halofantrin were investigated in a multi-centre study of 96 non immune patients (71 men, 25 women, mean age 34.3 [21-62] years) with malaria imported from regions of high resistance into Germany or Switzerland. The initial 63 patients received one-day treatment (three doses of 500 mg halofantrin), while the last 33 patients received an additional course of treatment one week later. Treatment was curative in all patients in the second group, but relapses occurred in five of the 41 patients (12.2%) with falciparum malaria who received one-day therapy. Fever resolved after a mean of 45 hours and parasites were absent after a mean of 66 hours. There were small increases in transaminase values (most probably because of the infection) in five patients, but all became normal again within a few days. Halofantrin is a safe drug and is suitable for both therapy and stand-by therapy of resistant Plasmodium infections. Treatment should be repeated after 7 days. PMID- 8444104 TI - [The therapy of hemochromatosis]. PMID- 8444103 TI - [Pseudoleukocytosis in cryoglobulinemia type I]. AB - During routine clinical and laboratory examinations of a symptom-free 54-year-old man a leukocytosis was repeatedly noted, but no cause found. 11 months later a painful spontaneously disappearing cyanosis occurred in two fingers of his right hand. Serum analysis demonstrated monoclonal type IgG-kappa immunoglobulin and an antinuclear antibody titre of 1:160. Skin biopsy suggested scleroderma. 4 months later, after exposure to cold, extensive acral haemorrhages occurred. Serum cryoglobulin concentration in serum was found to be 800 mg/dl. Comparative manual and electronic counts on warm and cooled blood identified the previously diagnosed leukocytosis as a typical artefact associated with cryoglobulinaemia. Treatment with chlorambucil (10-20 mg/d) and prednisolone (25 mg/d), for 14 days every 4 weeks, and finally interferon alpha-2b (5 mill. IU/d) reduced the cryoglobulin concentration to 150 mg/dl. Acral cyanosis and haemorrhages have not recurred since then. No cause of the cryoglobulinaemia has been found. PMID- 8444105 TI - [Protection after measles-mumps-rubella vaccination]. PMID- 8444106 TI - [The polymerase chain reaction and hepatitis B]. PMID- 8444107 TI - [Mental health and the social situation in old age]. PMID- 8444108 TI - [Endurance training in mild hypertension]. PMID- 8444109 TI - [The quality of life after the implantation of a cardioverter/defibrillator in malignant arrhythmias]. AB - Quality of life after implantation of an automatic implantable cardioverter/defibrillator (ICD) was assessed by questionnaire in 43 patients (38 males, 5 females; mean age 57 +/- 16 years) with treatment-resistant symptomatic ventricular arrhythmias. 37 of the 43 patients felt better after ICD implantation. 23 were always conscious of having an ICD, but 18 had got used to it in less than 2 months. 15 patients reported being afraid of an ICD shock, while eight noted physical discomfort caused by the ICD. Limitations concerning their professional, recreational and social activities were reported by six patients. 41 of the 43 patients confirmed that the ICD had been helpful, enabling 23 to return to an active life. 42 would recommend implantation to others if indicated. These data demonstrate that there is a remarkably high degree of acceptance of the ICD. Survival rate after implantation is thus not the only criterion of success. All aspects of the quality of life should be taken into consideration before implantation is decided upon. PMID- 8444110 TI - [Optic neuropathy in type-1 diabetes and acetylsalicylic acid-refractory thrombocyte activation]. AB - A 26-year-old female with severe complications from type I diabetes mellitus of 17 years' duration (proliferative retinopathy, nephropathy with renal failure and nephrotic syndrome) developed rapid deterioration of vision in the right eye to 6/60 over a period of several weeks. There were no other neurological signs. Ophthalmological examination showed no worsening of the diabetic retinopathy, but the presence of bilateral optic atrophy, confirmed by visual evoked potentials. CT scan did not reveal any retrobulbar process, and MR scans of both the optic nerves and the visual pathways were unremarkable. The clinical features and the investigations pointed towards ischaemic optic atrophy. Detailed platelet studies showed intravascular platelet activation and an ADP-inducible increase in aggregation, although thromboxane formation was almost absent because of cyclooxygenase inhibition by acetylsalicylic acid. These findings suggest that the ischaemia was due to microcirculatory disturbances secondary to diabetic microangiopathy and platelet hyperreactivity. PMID- 8444111 TI - [Mycobacterium genavense infection in AIDS]. AB - Fever, loss of weight, anaemia, hepatosplenomegaly and lymphadenopathy developed in two HIV-infected patients. At first malignant lymphoma with septicaemia was thought to be the cause. In both patients Salmonella enteritidis was isolated by blood culture and found to be sensitive against the antibiotics that were given (5 g azlocillin and 2 g cefotaxime, three times daily each; additionally in case 2, metronidazole, 500 mg three times daily). Because bone-marrow biopsy demonstrated acid-fast rods, antimycobacterial treatment was started (isoniazid 300 mg/d, rifampicin 600 mg/d, ethambutol 1,200 mg/d and pyrazinamide 2 g/d). Despite this the patients died of septic shock. Histological examination revealed massive amounts of acid-fast rods in spleen, liver, gut and bone marrow. Polymerase chain reaction and sequencing identified the structure as that of the recently discovered M. genavense. PMID- 8444112 TI - [The optimal preparation of native material for cytological diagnosis]. PMID- 8444113 TI - [The metabolic and endocrine functions of the cytokines]. PMID- 8444114 TI - [The physician in general practice in emergency service]. PMID- 8444115 TI - [The rejection of a medical authority because of prejudice. The decision of the Landgericht Dortmund of 10 September 1992]. PMID- 8444116 TI - [Thrombosis prophylaxis]. PMID- 8444118 TI - [Cyclosporin in severe bronchial asthma]. PMID- 8444117 TI - [Nephropathy in type-1 diabetes]. PMID- 8444119 TI - Normal anatomy of the vocal folds. PMID- 8444120 TI - Normal tympanic membrane. PMID- 8444121 TI - Sleep apnea and snoring, an overview. PMID- 8444123 TI - Muscles of the pharynx: structural and contractile properties. AB - Pharyngeal muscles are the effector organ by which the brainstem regulates pharyngeal airway size and patency during breathing. These muscles have fast contractile rates, and may be susceptible to develop fatigue when driven at the high levels required to overcome structural pharyngeal narrowing, especially under hypoxic conditions. Diseases with an increased prevalence of sleep apnea are associated with changes in pharyngeal muscle properties, and conversely diseases which primarily alter neuromuscular function have a significant prevalence of sleep apnea. However, further studies are needed to define the precise role of pharyngeal muscle fatigue, and of changes in pharyngeal muscle properties with disease, in the pathophysiology of obstructive sleep apnea. PMID- 8444122 TI - Epidemiology and natural history of obstructive sleep apnea. AB - The currently available data suggest that sleep apnea occurs commonly. Prevalence, however, varies markedly according to definitions utilized to characterize the disorder and the population studied; and has been reported to range from 1% (in an industrial working Israeli population) to 42% (in an elderly nursing home population). The degree to which sleep apnea contributes to the pathogenesis of other diseases is not entirely clear. Data from a number of sources suggest that sleep apnea may increase vascular morbidity and that excess mortality may occur in untreated patients. However, the degree to which mortality and morbidity may be influenced by more aggressive treatment of subjects with sleep apnea is not known. In particular, there is a need to better distinguish "clinically" significant sleep apnea from levels of apnea that may have few acute or chronic effects, and to define which segments of the population are at greatest risk for such adverse outcomes. PMID- 8444124 TI - Biochemical morbidity in sleep apnea. AB - The long-term goals of our research are to understand the biochemical morbidity surrounding obstructive sleep apnea syndrome to define better the need for treatment and to determine modifiable risk factors for the disease. Our current hypothesis is that sleep-related hypoxemia results in alterations in metabolic regulatory peptides, specifically insulin and insulin-like growth factors (IGF-1 and IGF-2), which are known or suspected factors for obesity and disorders such as hypertension, glucose intolerance, and atherosclerosis. Surveys of clinic populations suggest a relationship between body habitus, parameters of sleep disordered breathing, indices of oxygenation, and insulin resistance, defined by fasting serum levels of glucose and insulin. Results will provide insight into the role of metabolic regulatory peptides in the pathogenesis of sleep-disordered breathing and the mechanisms for this association. PMID- 8444125 TI - Properties of the upper airway during sleep. AB - Research efforts to date have identified that both anatomic and physiologic variables may contribute to the pathophysiology of obstructive sleep apnea. Whether specific factors within either of these two categories will be shown to predominate remains to be seen. Surely, experience with sleep apnea patients teaches us that different variables are important in different OSA patients. In the area of anatomy, investigators are just beginning to try surgical approaches designed specifically for the pharyngeal site of obstruction found in a given patient. Possible new physiologic and pharmacologic treatments are being explored. Hopefully, such treatments will be as effective and more convenient than continuous positive airway pressure. PMID- 8444126 TI - Uvulopalatopharyngoplasty: strategies for success and safety. AB - Management of snoring and/or obstructive sleep apnea patients may include uvulopalatopharyngoplasty, a surgical operation that occasionally generates complications. The most serious are perioperative airway problems and palatal dysfunction. Strategies to minimize risks and maximize efficacy are discussed. PMID- 8444127 TI - Neurostimulation for obstructive sleep apnea: investigations. AB - Neurostimulation of the upper airway muscles (accessory muscles of respiration) was accomplished in anesthetized dogs and sleeping humans by electrical stimulation of the hypoglossal nerves. Such stimulations relieved partial airway obstructions in dogs. They also aborted (shortened) obstructive sleep apnea events in humans who suffer with obstructive sleep apnea syndrome. In one subject, stimulations delivered in advance of apneic events (by automatic cycling) prevented apneas. Neurostimulation for obstructive sleep apnea may be an important concept for future research and development. PMID- 8444128 TI - Diagnosis and pathophysiology of obstructive sleep apnea in children. AB - Factors that decrease pharyngeal size or increase pharyngeal compliance increase an individual's risk for OSA. In children, these factors include craniofacial disorders, central nervous system problems, or simply adenotonsillar hypertrophy. Although children with OSA may present with nocturnal symptoms of snoring, respiratory pauses, secondary enuresis, and/or nightmares, their initial complaint may be poor school performance, hyperactivity, or other symptoms of sleep fragmentation. The diagnosis is confirmed by overnight polysomnography in a laboratory with expertise in the care of infants and children. PMID- 8444129 TI - The emerging epidemic of resistant pneumococci. PMID- 8444130 TI - Sleep studies--polysomnography. PMID- 8444131 TI - Uvulopalatopharyngoplasty for obstructive sleep apnea in adults: clinical correlation with polysomnographic results. AB - The success of Uvulopalatopharyngoplasty (UPPP) for Obstructive Sleep Apnea (OSA) can be assessed by a variety of parameters including clinical evaluation and polysomnography (PSG). Patients are often reluctant to undergo post-operative testing and insurance companies are often unwilling to reimburse for expensive overnight sleep studies. Due to the reality of these medical and economical problems, can a clinician be confident of the success of UPPP based solely on clinical evaluation? Sixty patients underwent UPPP for the treatment of OSA from July 1987 through June 1992. Patients treated with tracheostomy or other methods were not included in this study. Fifty-three patients (88%) reported an improvement in their symptoms of snoring, daytime somnolence, morning headache and apnea. Twenty-one patients (35%) had post-operative PSG. Eighteen of 21 patients (85%) reported improvement in their symptoms. Eleven of 21 patients (57%) showed objective improvement in their sleep apnea. The objective findings of PSG do not correlate, in a significant number of patients, with subjective clinical improvement of patients treated with UPPP. PMID- 8444132 TI - Obstructive sleep apnea syndrome: pathophysiology, upper airway evaluation and surgical treatment. AB - This paper describes the pathophysiology of the upper airway and the methods of evaluation which include mainly the Mueller maneuver, and cephalometrics. The management of Obstructive Sleep Apnea Syndrome (OSAS) is determined by the level of daytime dysfunction, the degree of cardiopulmonary complications, age, co existing medical problems, life style, and the extent of the upper airway obstruction and abnormality. Continuous positive airway pressure (C-PAP), uvulopalatopharyngoplasty (UPPP), and permanent tracheostomy are procedures indicated depending on the severity of the case. Midline laser glossectomy was introduced as a new surgical procedure approach to the treatment of OSAS, as an alternative to maxillofacial surgery. When combined with UPPP, the successful results are improved. PMID- 8444133 TI - Treatment of otherwise normal children with obstructive sleep apnea. AB - There are many therapeutic approaches to children with OSA. Treatment should be considered only when the severity of the syndrome has been established by objective testing including overnight polysomnography. Anatomic abnormalities, including adenotonsillar hypertrophy, must be defined. Once the severity and underlying cause of OSA have been established, the most appropriate approach can be devised for the individual. Mild cases may simply be observed. Moderate or severe patients whose nasopharynx is obstructed by lymphoid hyperplasia may be treated with adenotonsillectomy. If surgery is declined or contraindicated, nasal CPAP is effective. CPAP is also useful as a temporary measure while weight loss is being effected. PMID- 8444134 TI - Sleep apnea in the neurologically-impaired child. PMID- 8444135 TI - The role of nasal obstruction in obstructive sleep apnea syndrome. AB - In summary, there is much evidence in the literature that nasal obstruction causes obstructive sleep apnea, usually of mild to moderate degree, in many individuals. In addition, it is a contributory factor in individuals with severe obstructive sleep apnea. This appears to occur because of its contribution to upper airway resistance which directly or indirectly results in a reduction in intraluminal pressure during inspiration and collapse. Nasal obstruction via its influence on the so-called nasal-pulmonary reflex, may also result in alveolar hypoventilation. In patients who have symptoms consistent with obstructive sleep apnea syndrome and/or other disorders of excessive somnolence, a careful history eliciting findings of possible nasal obstruction as well as a thorough nasal examination is appropriate. If nasal obstruction is present, intervention should be considered as part of the routine therapy for obstructive sleep apnea syndrome. PMID- 8444136 TI - Management of total nasopharyngeal stenosis following UPPP. AB - UPPP has emerged over the past decade as a surgical procedure to improve or possibly eliminate Obstructive Sleep Apnea. The procedure itself is not uniformly successful and the technique continues to undergo evolution. Most complications occur in the acute post-operative period and are not unusual. Late complications are seen much less frequently: less than 100 cases of severe nasopharyngeal stenosis have been reported. Several authors have previously identified this problem and have published "avoidance strategies" and we recommend that the UPPP surgeon be well aware of these pitfalls and the ways to avoid them. Stenosis repair using pharyngeal flaps should be the primary technique used to correct this problem. The radial forearm free flap provides the surgeon with another technique for repair of acquired nasopharyngeal stenosis in problem cases in which pharyngeal flap procedures have failed. As with any surgery, the surgeon must have a thorough understanding of the wound healing process. PMID- 8444137 TI - Breast-feeding and cognitive development. AB - Eight-hundred fifty-five newborns were enrolled in a prospective study between 1978 and 1982 and then followed through school age. To determine whether the mode of infant feeding affected developmental scores or school grades, prospective data were collected on how the children were fed; 788 of the children had Bayley tests at 6 months, 720 at 12 months, 676 at 18 months and 670 at 2 years. McCarthy testing was done on 645 children at 3 years, 628 at 4 years and 636 at 5 years. Testers were not specifically blind to feeding method. The families provided report cards from grade 3 or higher for 366 children. There were statistically significant but small increases in scores among breast-fed children on at least some subscales of the Bayley and McCarthy at all time points from 2 years through 5 years and slightly higher English grades on report cards in both crude analyses and in multivariate analyses that allowed adjustment for the most plausible confounding variables. We conclude that, in a volunteer, 95% white sample of middle class children, those breast-fed scored slightly better than those bottle fed; the effect is small but still detectable at school age. PMID- 8444138 TI - Changes with time in fetal heart rate variation, movement incidences and haemodynamics in intrauterine growth retarded fetuses: a longitudinal approach to the assessment of fetal well being. AB - Fetal heart rate (FHR) variation, general movements (FGM), breathing movements (FBM) and haemodynamics were studied longitudinally in 19 intrauterine growth retarded fetuses, who eventually were delivered by caesarean section (CS) because of fetal distress, in order to determine changes occurring with time. The fetuses were studied for the last 10 days on average before delivery (range 2-14 days). During this period on average eight 1-h FHR records were made and three 1-h movement recordings. The FHR pattern was analyzed numerically; the incidence of FGM and FBM was quantified and expressed as percentage of time. Blood flow velocity waveforms were measured in the umbilical artery (n = 19) and in the internal carotid artery (n = 14). In 14 of 19 fetuses abnormal velocity wave forms were present from the beginning of the study onwards. FHR variation was initially just within or below the norm and fell further during the last 2 days before CS. FGM and FBM fell below the normal range later and in a lower rate of occurrence than FHR variation. FGM showed a more or less consistent fall in time, whereas FBM showed a wide range throughout the period of observation. The poorest outcome occurred in fetuses with reversed end-diastolic velocities and rapid fall in FHR variation. It is concluded that with progressive deterioration of the fetal condition abnormal velocity wave form patterns occur first; FHR variation is reduced subsequently and FGM and FBM are the last to become abnormal. Assessment of fetal activity may be of help in fetuses with a marginally reduced FHR variation, in which prolongation of pregnancy is considered desirable to allow further maturation in utero. PMID- 8444139 TI - Effect of gender on blood pressure levels of very low birthweight infants in the first 48 hours of life. AB - Systolic blood pressure was measured in 98 very low birthweight (VLBW) infants in the first 48 h of life. Measurements were made on 49 male infants, median gestational age 29 weeks and 49 female infants who were matched with the male infants for gestational age. Blood pressure was measured either from an indwelling arterial line or non-invasively using a Doppler technique; measurements were made on all infants on day 1 and day 2. In both male and female infants on day 1 and day 2, blood pressure levels correlated significantly with gestational age (P < 0.01). On day 1, but not on day 2, the blood pressure of the male infants was significantly lower than the female infants. We conclude it is important to use gender appropriate regression equations for blood pressure in VLBW infants in the first 24 hours of life. PMID- 8444140 TI - Heart rate variability in healthy term newborns: the contribution of respiratory sinus arrhythmia. AB - Cardiorespiratory interactions in healthy full term newborns were investigated. Spectral analysis was used on heart rate and breathing data from 22 neonates 2-5 days old to reveal coincident frequencies in the breathing and heart rate variability (HRV) spectra, thus identifying respiratory sinus arrhythmia (RSA). The spectral description of HRV in healthy term newborns revealed a consistent and distinct RSA feature, with a mean contribution of over 30%. The contribution of RSA to HRV was dependent on breathing frequency and absolute RSA power. The mechanisms that produce this cardiorespiratory interaction are considered to be functionally active in the healthy term neonate. PMID- 8444141 TI - Dosing regimens for transgenic animal mutagenesis assays. PMID- 8444142 TI - How much do we know about spontaneous human mutation rates? AB - The much larger number of cell divisions between zygote and sperm than between zygote and egg, the increased age of fathers of children with new dominant mutations, and the greater evolution rate of pseudogenes of the Y chromosome than of those on autosomes all point to a much higher mutation rate in human males than in females, as first pointed out by Haldane [Ann Eugen 13:262-271, 1947] in his classical study of X-linked hemophilia. The age of the father is the main factor determining the human spontaneous mutation rate, and probably the total mutation rate. The total mutation rate in Drosophila males of genes causing minor reduction in viability is at least 0.4 per sperm, and may be considerably higher. The great mutation load implied by a rate of approximately 1 per zygote can be greatly ameliorated by quasi-truncation selection. Corresponding data are not available for the human population. The evolution rate of pseudogenes in primates suggests some 10(2) new mutations per zygote. Presumably the overwhelming majority of these are neutral, but even the approximate fraction is not known. Statistical evidence in Drosophila shows that mutations with minor effects cause about the same heterozygous impairment of fitness as those that are lethal when homozygous. The magnitude of heterozygous effect is such that almost all mutant genes are eliminated as heterozygotes before ever becoming homozygous. Although quantitative data in the human species are lacking, anecdotal information supports the conclusion that partial dominance is the rule here as well. This suggests that if the human mutation rate were increased or decreased, the effects would be spread over a period of 50-100 generations. PMID- 8444143 TI - Effects of methyl methanesulfonate on mouse sperm chromatin structure and testicular cell kinetics. AB - Effects of methyl methanesulfonate (MMS) on mouse testicular cell kinetics and sperm chromatin structure were determined flow cytometrically. Mice were exposed to a single ip injection of saline containing 0 or 150 mg/kg MMS. Relative ratios of 1N, 2N and 4N testicular cells were not affected until 22 days postexposure. Ratios of 1N cell types were altered from 13 to 22 days and were near normal by 25 days. This study revealed an MMS induced alteration of chromatin structure in testicular, elongated spermatids by the sperm chromatin structure assay (SCSA), a flow cytometric measure of the susceptibility of acridine orange stained sperm DNA to denaturation in situ. The SCSA also detected alterations in cauda sperm chromatin structure at 3 days, which was 8 days prior to alterations in sperm head morphology, indicating the increased sensitivity of the SCSA. SCSA data were practically similar whether measuring either fresh or frozen/thawed sperm, or whether measured by two different types of flow cytometers: a) laser driven, orthogonal optical axis; or b) low cost mercury arc lamp system with epiillumination. The data support the model of Sega and Owens [Mutat Res 111:227 244:1983] that MMS alkylates cysteine-SH groups in sperm protamines, thereby destabilizing sperm chromatin structure and leading to broken chromosomes and mutations. PMID- 8444144 TI - Evaluation of a three-exposure mouse bone marrow micronucleus protocol: results with 49 chemicals. AB - Forty-nine chemicals were tested in a mouse bone marrow micronucleus test that employed three daily exposures by intraperitoneal injection. Bone marrow samples were obtained 24 hr following the final exposure. Twenty-five rodent carcinogens and 24 noncarcinogens were selected randomly from the 44 carcinogens and 29 noncarcinogens used by Tennant et al. (Science 236:933-941, 1987) to evaluate the performance of four in vitro genetic toxicity tests. As in that study of in vitro tests, the micronucleus tests were conducted with coded chemicals and test results (positive or negative) were determined prior to decoding. This study was conducted as part of an effort to assess the ability of the micronucleus test to discriminate between rodent carcinogens and noncarcinogens and to determine its potential role, in combination with other short-term tests, in identifying genotoxic chemicals that present a carcinogenic hazard. Nine chemicals were judged to be positive in the micronucleus test. This relatively low number of positive results, along with published and unpublished results from rodent micronucleus and chromosome aberration assays on several of these 49 chemicals, contributed to the conclusion that a single micronucleus test protocol is not adequate to detect all chemicals capable of inducing chromosomal damage in the bone marrow. However, a combination of two relatively simple assays such as the Salmonella and micronucleus tests can provide important information on the genetic toxicity of test chemicals and may provide guidance on the need for and the nature and extent of future toxicity studies. PMID- 8444145 TI - Analysis of the six additional chemicals for in vitro assays of the European Economic Communities' EEC aneuploidy programme using Saccharomyces cerevisiae D61.M and the in vitro porcine brain tubulin assembly assay. AB - We tested six additional chemicals (acetaldehyde, benomyl, diethylstilboestrol, diethylstilboestrol dipropionate, griseofulvin, and mercaptoethanol) for in vitro systems of the coordinated programme to study aneuploidy induction sponsored by the Commission of the European Communities in two in vitro test systems. Using Saccharomyces cerevisiae D61.M (mitotic chromosomal malsegregation assay), benomyl showed a dose-dependent increase in the frequency of chromosomal malsegregation with a lowest effective dose tested (LEDT) of 30 micrograms/ml (0.1 mM). Diethylstilboestrol (DES) showed solvent-dependent effects. DES dissolved in ethanol induced an increase in chromosomal malsegregation as well as in the frequency of total resistant colonies (mutations and recombinations) with a LEDT around 13 micrograms/ml (0.048 mM). Using dimethylsulfoxide as the solvent, no increases were observed with DES up to 333 micrograms/ml (1.24 mM). Acetaldehyde induced an increase in chromosomal malsegregation with the cold treatment protocol (LEDT: 1.25 microliters/ml (21 mM) and 0.75 microliters/ml (13 mM), respectively) but no increase with the overnight protocol (highest dose tested (HDT): 1.75 microliters/ml; 30 mM). Concerning the frequency of total cycloheximide-resistant colonies (mutations and recombinations) increases were obtained with both protocols. The other three compounds were negative when tested up to toxic doses (survival below 10%), up to the maximum solubility in the solvent used or up to heavy precipitation in the incubation mix. The HDT were 333 micrograms/ml (0.88 mM) for diethylstilboestrol dipropionate, 1,600 micrograms/ml (4.5 mM) for griseofulvin and 0.5 microliters/ml (7 mM) for mercaptoethanol. Concerning effects on porcine brain tubulin assembly in vitro, diethylstilboestrol and griseofulvin inhibited the assembly process. The IC30% (30% inhibition concentration) values were 12.5 microM and 100 microM for DES and griseofulvin, respectively. Mercaptoethanol showed no effects up to 50 mM. PMID- 8444146 TI - Structural relationships between mutagenicity, maximum tolerated dose, and carcinogenicity in rodents. AB - The CASE structure-activity relational system was applied to a study of the structural bases of toxicity as expressed in the maximum tolerated dose (MTD) of a group of chemicals for which rodent carcinogenicity and mutagenicity data were also available. All of the results were obtained under the aegis of the U.S. National Toxicology Program. The analyses revealed that there was a structural basis for the MTD in mice and in rats and that these overlapped considerably. There was also some overlap between structural determinants of the MTD and of carcinogenicity in rodents but there was also a significant "antagonism" between such fragments; i.e., fragments associated with high toxicity (low MTD) were associated with lack of carcinogenicity and vice versa. The highest overlaps observed were between the structural determinant for a low MTD (i.e., high toxicity) and mutagenicity in Salmonella. PMID- 8444147 TI - RNA polymerase III. Genes, factors and transcriptional specificity. AB - Recent studies on RNA polymerase III (pol III) gene transcription have provided a new awareness of the molecular complexity of this process. Fortunately, while the number of transcription components has been increasing, fundamental similarities have emerged regarding the function of eukaryotic promoter elements and the factors that bind them to form preinitiation complexes. Among these, the ability of transcription factor IIIB (TFIIIB) and pol III to transcribe the Saccharomyces cerevisiae U6 gene suggests that the concept of a minimal pol II promoter comprising a TATA box and an initiator region has a parallel in the pol III system. Furthermore, for each of the three classes of eukaryotic RNA polymerase, the assembly of transcription preinitiation complexes and, to some extent, the nature of these complexes appears to be more similar than was previously anticipated. This work highlights the novel functions and transcriptional properties of newly identified pol III genes, discusses the diversity of pol III promoter structures and presents the notion that the exclusive use of extragenic promoters by some pol III genes (so-called type-3 genes) may have evolved since the divergence of yeast and higher eukaryotes. Additionally, recent progress is reviewed on the identification and cloning of subunits for TFIIIC and TFIIIB. Particular emphasis is given to two components of TFIIIB, the TATA-binding protein and a protein with TFIIB homology (PCF4), since the properties of these molecules suggest a model whereby the polymerase specificity of transcription complexes is determined. PMID- 8444148 TI - The formation of methylglyoxal from triose phosphates. Investigation using a specific assay for methylglyoxal. AB - In Krebs-Ringer phosphate buffer, the rate of formation of methylglyoxal from glycerone phosphate and glyceraldehyde 3-phosphate was first order with respect to the triose phosphate with rates constant values of 1.94 +/- 0.02 x 10(-5) s-1 (n = 18) and 1.54 +/- 0.02 x 10(-4) s-1 (n = 18) at 37 degrees C, respectively. The rate of formation of methylglyoxal from glycerone phosphate and glyceraldehyde 3-phosphate in the presence of red blood cell lysate was not significantly different from the non-enzymatic value (P > 0.05). Methylglyoxal formation from glycerone phosphate was increased in the presence of triose phosphate isomerase but this may be due to the faster non-enzymatic formation from the glyceraldehyde 3-phosphate isomerisation product. For red blood cells in vitro, the predicted non-enzymatic rate of formation of methylglyoxal from glycerone phosphate and glyceraldehyde 3-phosphate may account for the metabolic flux through the glyoxalase system. The reactivity of glycerone phosphate and glyceraldehyde 3-phosphate towards the non-enzymatic formation of methylglyoxal under physiological conditions suggests that methylglyoxal formation is unavoidable from the Embden-Meyerhof pathway. PMID- 8444149 TI - Specificity of Streptomyces griseus aminopeptidase and modulation of activity by divalent metal ion binding and substitution. AB - Streptomyces griseus aminopeptidase is a calcium-activated zinc metalloenzyme characterized by a high enzymic reactivity, high thermal stability and low molecular mass [Spungin, A. and Blumberg, S. (1989) Eur. J. Biochem. 183, 471 477]. A study of the specificity of S. griseus aminopeptidase using amino acid 4 nitroanilide substrates shows that the leucine derivative is the best substrate. Derivatives of other hydrophobic amino acids, methionine and phenylalanine, are also excellent substrates for the enzyme. The 4-nitroanilides of alanine, valine, proline and lysine are good substrates whereas those of the small size glycine and the acidic amino acids are very poor. No hydrolysis of a terminal Xaa residue can be detected with Xaa-proline N-terminal sequences. Calcium ions bind to the enzyme and modulate its activity in a substrate-dependent manner. The catalytically essential zinc of S. griseus aminopeptidase is removed by dialysis against 1,10-phenanthroline and replaced by manganese or cobalt ions, resulting in enzyme derivatives of altered specificities. Thus, whereas the zinc enzyme hydrolyzes leucine 4-nitroanilide at a 10-fold faster rate than the manganese or cobalt enzymes, the cobalt enzyme hydrolyzes alanine 4-nitroanilide at a more than 20-fold faster rate than the zinc or manganese enzymes. PMID- 8444150 TI - Purification and characterization of recombinant human beta 1-4 galactosyltransferase expressed in Saccharomyces cerevisiae. AB - A protease-defective strain of Saccharomyces cerevisiae (BT 150) was used to express full-length cDNA of HeLa cell beta-D-N-acetylglucosaminide-beta-1,4 galactosyltransferase (gal-T). To ascertain import of the recombinant gal-T into the secretory pathway of yeast cells, metabolically labeled enzyme was immunoprecipitated from extracts of yeast transformants, analysed by SDS/PAGE/fluorography and tested for sensitivity to treatment with endoglycosidase-H. Untreated recombinant gal-T had an apparent molecular mass of 48 kDa, which was reduced to 47 kDa after treatment, indicating that the recombinant enzyme was N-glycosylated and, therefore, competent for translocation across the membranes of the endoplasmic reticulum. Using specific gal-T assays employing N-acetylglucosamine or glucose in combination with alpha-lactalbumin as exogenous acceptor substrates, recombinant gal-T enzyme activity could readily be detected in crude homogenates. Analysis of the disaccharide products by 1H-NMR spectroscopy demonstrated that only beta-1-4 linkages were formed by the recombinant gal-T. The recombinant gal-T was detergent solubilized and subsequently purified by affinity chromatography on N-acetylglucosamine derivatized Sepharose followed by alpha-lactalbumin-Sepharose. The purified enzyme preparation had a specific activity comparable to that of the soluble gal T isolated from human milk. Furthermore, kinetic parameters determined for both acceptor and donor substrates of both enzymes differed only slightly. This work shows that yeast provides an appropriate host system for the heterologous expression of mammalian glycosyltransferases. PMID- 8444151 TI - Purification and characterization of a coenzyme-A-dependent succinate semialdehyde dehydrogenase from Clostridium kluyveri. AB - Cell extracts of Clostridium kluyveri, grown on ethanol plus succinate contained a succinyl-CoA:CoA transferase (0.28 U/mg), a coenzyme-A-dependent succinate semialdehyde dehydrogenase (0.73 U/mg) and a NAD(+)-dependent 4-hydroxybutyrate dehydrogenase (0.25 U/mg). The semialdehyde dehydrogenase, which catalyzed the NADPH-dependent reduction of succinyl-CoA to succinate semialdehyde, was purified 59-fold to homogeneity. A molecular mass of 115000 Da was determined for the native enzyme; SDS/PAGE revealed one protein band at 55,000, indicating that the active form is a dimer. The enzyme was highly specific for succinyl-CoA and succinate semialdehyde. The pH optimum was 7.0 for the reduction of succinyl-CoA, and 8.5 for the reverse reaction. Km values were determined for both the forward and reverse directions. The kinetic data suggest a ping-pong mechanism. PMID- 8444152 TI - An upstream region of the rat spermatogenesis-specific heat-shock-like Hst70 gene confers testis-specific expression in transgenic mice. AB - In order to study the temporal and spatial regulation of a rat testis-specific heat-shock-like hst70 gene, an 0.8-kb fragment of its upstream DNA was fused to the lacZ gene and microinjected into one-cell murine embryos. Independent tgHST1 and tgHST2 transgenic mice strains were established, containing about 5-7 and 40 60 transgene copies/haploid genome, respectively. Enzyme assays in various tissues showed that transgene-encoded beta-galactosidase accumulates exclusively in testes of transgenic animals and cannot be detected until 16-17 days after birth. In-situ assays revealed that the enzyme accumulates mainly in pachytene primary spermatocytes. Our data complement previous studies on the endogenous rat hst70 and suggest that its 0.8-kb upstream region contains sufficient information to function as an active spermatogenesis-specific promoter. PMID- 8444153 TI - Effects of subsite alterations on substrate-binding mode in the active site of hen egg-white lysozyme. AB - The subsite structures in the active site of hen egg-white lysozyme were altered by site-directed mutagenesis. Replacement of Trp62, which is involved in apolar interaction with a sugar ring, and Asp101, which is hydrogen bonded to the same sugar ring in subsite B, led to a shift of the oligosaccharide-binding mode in the active-site cleft. Consequently, the double-mutant lysozyme (Trp62His, Asp101Gly) exhibited a drastic change of substrate-binding without any significant loss of enzymic activity. Conversion of Asn37, which is postulated to be involved in interaction with a sugar ring in subsite F, had a reverse effect on substrate binding. Nuclear magnetic resonance analysis of mutant lysozymes, in which Trp62 was replaced with Phe or His, suggested that these replacements not only altered the structure of the amino acid chain at position 62 of the lysozyme, but also induced local structural changes around the residue at position 62. PMID- 8444154 TI - Identification of a nuclear protein that constitutively recognizes the sequence containing a heat-shock element. Its binding properties and possible function modulating heat-shock induction of the rat heme oxygenase gene. AB - Heme oxygenase is an essential enzyme in heme catabolism, and also known as a 32 kDa heat-shock protein in rat. The rat heme-oxygenase gene promoter contains a functional heat-shock element (HSE) designated as HSE1 (-290 to -276 from the transcriptional initiation site), which consists of three copies of a 5-bp unit (5'-NGAAN-3';-->) in alternating orientation. Here we identified a putative HSE ( 221 to -212), designated as HSE2, consisting of an inverted repeat of this 5-bp unit (<==>). Using transient expression assays, we show that HSE1 is sufficient to confer the heat-inducibility (a three fold to fourfold increase) on the reporter gene located downstream from the rat heme-oxygenase gene promoter, but HSE2 alone is not, suggesting that HSE2, a HSE of a tail-to-tail configuration, is not functional in vivo. However, the presence of both HSE1 and HSE2 in the promoter region increased the heat-mediated induction of the reporter-gene expression by more than 15-fold. Gel mobility-shift assays indicate that both HSE1 and HSE2 are recognized by activated heat-shock factor present only in heat shocked rat glioma cells. Interestingly, the sequence containing HSE2 is also bound by a protein that is present in nuclear extracts prepared from either heat shocked or non-shocked glioma cells, but this nuclear protein is unable to bind to HSE1. We suggest that a protein binding to the sequence containing HSE2 may be involved in transcriptional regulation of the rat heme oxygenase gene under thermal stress. PMID- 8444155 TI - Thymidine phosphorylase activity of platelet-derived endothelial cell growth factor is responsible for endothelial cell mitogenicity. AB - Recombinant human platelet-derived endothelial cell growth factor, expressed in the yeast Saccharomyces cerevisiae was purified to greater than 98% purity by anion-exchange and hydroxyapatite chromatography. It was shown to possess thymidine phosphorolytic activity in vitro (pH optimum, pH 5.3; Km, 0.11 mM; Vmax, 12.5 mmol min-1 mg-1; turnover number, 9.4 s-1). Covalent modification simultaneously inhibited the enzymatic and mitogenic properties of the protein, while interaction with a cell-surface receptor was not required to stimulate mitogenesis. Purified Escherichia coli thymidine phosphorylase was also mitogenic toward endothelial cells. It is proposed that platelet-derived endothelial cell growth factor is human thymidine phosphorylase which promotes endothelial cell proliferation by reducing thymidine levels that would otherwise be inhibitory to endothelial cell growth. PMID- 8444156 TI - Alternative pre-rRNA processing pathways in human cells and their alteration by cycloheximide inhibition of protein synthesis. AB - rRNA processing pathways in humans have been reinvestigated through systematic Northern-blot hybridizations of HeLa cell nuclear RNA with a collection of digoxigenin-labeled rDNA probes from different regions of the human rDNA transcriptional unit. In addition to the known 45S, 41S, 32S and 21S pre-rRNA, two major pre-rRNA fractions were identified; a '30S' (about 5800 nucleotides) precursor to 18S rRNA containing an external transcribed spacer at the 5' end (ETS) and internal transcribed spacer (ITS) 1 sequences and a '12S' (about 950 nucleotides) precursor to 5.8S rRNA containing ITS 2 sequences. These pre-rRNA species do not react with probes located near the 3'-terminal segments of ITS 1 or ITS 2, thus suggesting that processive endonuclease cuts occur within ITS spacer sequences. The simultaneous occurrence of at least two alternative 45S pre rRNA processing pathways is deduced, which correspond to a different temporal order of endonuclease attack at the sites located near the 5' end of 18S rRNA and within ITS 1. In-vivo labeling experiments with [14C]uridine revealed that inhibition of protein synthesis with cycloheximide abolishes the endonuclease cut at the 5' end of 18S rRNA and the formation of 41S pre-rRNA, while the cut within ITS 1 and the processing to 32S and '30S' pre-rRNA remains relatively unaltered. PMID- 8444157 TI - Beta-actin mRNA-binding proteins associated with the cytoskeletal framework. AB - Association of mRNA with the cytoskeletal framework (CSK) is thought to play a strategic role in the placement of mRNA in the cytoplasm. However, the molecular determinants underlying mRNA/CSK association are completely unknown. To begin addressing this issue, we have employed a binding assay to identify proteins of the CSK compartment of NIH 3T3 cells that bind in-vitro-transcribed 32P-labelled beta-actin mRNA with high affinity. Three proteins, of approximate molecular masses 27, 50 and 97 kDa, were observed to exhibit strong binding. Binding to these proteins took place at physiological salt concentration and withstood washing in 0.5 M salt. Furthermore, binding was unaffected by heparin but was inhibited by unlabelled beta-actin mRNA. Treatment of isolated CSKs with the microfilament-severing agent DNase I abolished all beta-actin mRNA-binding activities, thus suggesting a possible association of beta-actin mRNA with the microfilament network in situ. Removal of the 3' untranslated region (UTR) significantly reduced beta-actin mRNA binding to all three CSK proteins but removal of the 5' UTR mainly affected binding to the 97-kDa species and that to a lesser extent. beta-Tubulin mRNA bound to the same three CSK proteins as did beta actin mRNA, but with considerably less avidity. In contrast, vimentin mRNA strongly recognized these CSK proteins, and further bound to a group of smaller proteins (< 29 kDa). As beta-actin mRNA, beta-tubulin mRNA and vimentin mRNA have been observed to occupy separate cytoplasmic locales, the proteins detected here may be operative both in binding mRNAs to the CSK in situ, as well as in localizing mRNA in the cytoplasm. PMID- 8444158 TI - A step towards understanding the folding mechanism of horseradish peroxidase. Tryptophan fluorescence and circular dichroism equilibrium studies. AB - The guanidinium chloride denaturation/renaturation of the holo- and apo horseradish peroxidase isoenzyme c (HRP) has been studied by fluorescence and circular dichroism spectroscopies. A distinct equilibrium intermediate of the apoprotein could be detected at low concentrations of guanidinium chloride (0.5 M). This intermediate has a secondary structure content like that of the native protein but a poorly defined tertiary structure. Renaturation of the apo-HRP is reversible and 100% activity could be obtained after addition of a twofold excess of free haem. The denaturation of the holo-HRP is more complex and occurs in two distinct steps; unfolding of the protein backbone and loss of the haem. The denatured protein folds back to its native conformation but the incorporation of the haem occurs only after the secondary structure is formed. Ca2+ appears to be important for the stability of the protein as the apo-HRP is more resistant to denaturation in the presence of Ca2+. The free-energy change during unfolding of the apo-HRP was determined in the absence and presence of Ca2+ and found to be 9.2 kJ/mol and 16.7 kJ/mol, respectively. The importance of Ca2+ to the protein stability was also supported by studies on the loss of the haem from the protoporphyrin-IX-apo-HRP complex. PMID- 8444159 TI - Cooperative effects on filament stability in actin modified at the C-terminus by substitution or truncation. AB - We have studied the contribution of the C-terminus of actin to filament stability by chemical modification and limited proteolysis. Formation of mixed disulfides of the penultimate C-terminal cysteine residue 374 with various low-molecular mass thiols resulted in filament destabilization, as reflected by an increase in critical concentration and steady-state ATPase activity. These effects were fully reversed by the addition of phalloidin. Both the destabilization by glutathionylation and the reversal of it by phalloidin exhibited a high degree of cooperativity; half-maximal destabilization required the modification of four out of five actin subunits, and half-maximal restabilization by phalloidin was already reached when only one out of 20 actin subunits was complexed. C-terminal truncation by limited trypsinolysis of filamentous actin resulted in a similar destabilization of the polymer, as shown by a 2-3-fold increase in the steady state ATPase activity. This effect was likewise cooperative and could be reversed by phalloidin. Since truncation of the C-terminus of actin has an effect on stability similar to that of chemical modification with bulky substituents, the possibility can be excluded that, in the latter case, destabilization was caused by steric hindrance. Rather, it seems that the highly conserved C-terminal part of actin plays an active role in establishing a tight contact between neighbouring subunits. PMID- 8444160 TI - Specific synthesis of adenosine(5')tetraphospho(5')nucleoside and adenosine(5')oligophospho(5')adenosine (n > 4) catalyzed by firefly luciferase. AB - Luciferase catalyzes the preferential synthesis of adenosine(5')tetraphospho(5')nucleoside (Ap4N) in the presence of luciferin (LH2), adenosine 5'-[gamma-thio]triphosphate (ATP[gamma S]) and NTP (other than ATP), with very low, or undetectable synthesis of Ap4A or Np4N, because ATP[gamma S] is a good adenylyl donor for the formation of the E-LH2-AMP complex, but a poor adenylyl acceptor from the complex, and NTP, other than ATP, are bad nucleotidyl donors, but good acceptors of the AMP moiety of the E-LH2-AMP complex. Synthesis of the corresponding Ap4N (or Ap5G in the case of p4G were obtained in the presence of ATP[gamma S] and GTP, UTP, CTP, XTP, dTTP, ITP, dGTP, dCTP, dITP, epsilon ATP (epsilon A, N6-ethenoadenosine) or p4G. The yield of synthesis of Ap4N was at least 50% of that theoretically expected. The process can be easily scaled-up, which allows synthesis of at least 1-5 mumol Ap4N. Further evidence for the synthesis of Ap4G from ATP[gamma S] and GTP was obtained by 1H-NMR and 31P-NMR spectroscopy. Synthesis of Ap4N, in yields lower than those above, can also be obtained in the presence of ADP and NTP; synthesis is due to the presence in commercial luciferase of enzymes (adenylate kinase and NDP kinase) that catalyze the synthesis of ATP from ADP and NTP. In the presence of ATP and polyphosphates, luciferase catalyzes the synthesis of a variety of compounds of adenosine 5'-polyphosphates (pnA; n = 3-20 and ApnA; n = 4-16). In the presence of P3 or P4, preferential synthesis of p4A and Ap5A or p5A and Ap6A were obtained, respectively, showing that both polyphosphates accept the adenylyl moiety of the E-LH2-AMP complex. Polyphosphates of chain length 5, 15 and 35 elicited the synthesis of a variety of PnA and ApnA. Ap4A is also split by luciferase in the presence of P3 or P4 (but not in the presence of P5) yielding preferential synthesis of p4A and Ap5A, or p5A and Ap6A, respectively. PMID- 8444161 TI - Isolation of a ripening and wound-induced cDNA from Cucumis melo L. encoding a protein with homology to the ethylene-forming enzyme. AB - A cDNA clone (pMEL1) was isolated from a climacteric melon fruit cDNA library using the tomato ethylene-forming-enzyme (EFE) cDNA, pTOM13, as a probe. Northern analysis of RNA isolated from wounded leaf and fruit tissue and from preclimacteric and climacteric pericarp tissue was used to determine the pattern of pMEL1 RNA expression. pMEL1 hybridized to a 1.3-kb transcript in climacteric fruit and wounded leaf tissue but was undetectable in preclimacteric fruit and unwounded leaves. Maximal expression of pMEL1 RNA occurred in wounded ripe fruit. pMEL1 contained a 1230-bp insert containing a predicted open reading frame of 318 amino acids and molecular mass of 35.3 kDa. The predicted amino acid sequence of pMEL1 was 73-81% identical to the deduced amino acid sequences of tomato (pTOM13) EFE and EFE-related genes isolated from tomato and avocado fruit and senescent carnation petals. Genomic Southern analysis indicated that pMEL1 hybridized to a number of genomic fragments consistent with the presence of more than one pMEL1 related gene in melon. On Western analysis of total protein extracts from ripe tomato and melon fruit, using an antibody raised against tomato EFE (pTOM13) expressed in Escherichia coli, a single 35.5-kDa protein was detected. A 35-kDa product translated from in-vitro transcribed pMEL1 and immunoadsorbed by anti-EFE serum was very similar in size to the predicted 35.3-kDa pMEL1 cDNA protein product. These results indicate that pMEL1 may encode an EFE gene involved in ethylene biosynthesis during fruit ripening and may be identical to or share extensive sequence similarity with an EFE expressed in response to tissue wounding. PMID- 8444162 TI - Retraction concerning the E2 protein of human papillovirus type 16: overexpression and purification of an active transcriptional regulator [Lees, M.E., Dreissen, H.P.C., Crawford, L.V. & Clarke, A.R. (1990) Eur. J. Biochem. 190, 85-92.] Expression of the human papillovirus type 16 E2 protein in Escherichia coli. PMID- 8444163 TI - Isolation and identification of N-terminally extended forms of 5 oxoprolylglutamylprolinamide (Glp-Glu-Pro-NH2), a thyrotropin-releasing-hormone (TRH)-like peptide present in human semen. AB - N-terminally extended forms of 5-oxoprolylglutamylprolinamide (Glp-Glu-Pro-NH2), a thyrotropin-releasing-hormone(TRH)-like peptide associated with the male reproductive system, were isolated from human semen by gel exclusion on Sephadex G50, ion-exchange chromatography on SP-Sephade C25 and QAE-Sephadex A25, and by HPLC. The peptides were located by trypsin-catalysed release of their C-terminal fragments which were detected by RIA with a TRH-specific antibody. A series of overlapping peptides containing 16, 18, 22 and 25 residues was obtained in homogeneous form and their sequences were determined by automatic Edman degradation. The peptides all terminated in -Lys-Gln-Glu-Pro-NH2 and were found to correspond to sequences occurring between residues 350-374 of semenogelin, a protein present in human semen. In semenogelin, however, the Gln-Glu-Pro sequence is followed by tryptophan and not glycine which is normally essential for formation of the C-terminal amide group. Model experiments with the synthetic peptide Glp-Glu-Pro-Trp showed that under a range of experimental conditions the tetrapeptide did not undergo conversion to Glp-Glu-Pro-NH2. This would indicate that the tripeptide and its extended forms are generated from a precursor that is related to semenogelin but in which Trp375 is replaced by glycine. PMID- 8444164 TI - Glucose-6-phosphate dehydrogenase. Structure-function relationships and the Pichia jadinii enzyme structure. AB - The primary structure of glucose-6-phosphate dehydrogenase from the yeast Pichia jadinii (formerly Candida utilis) has been determined. It consists of a 495 residue, N-terminally acetylated protein chain. The structure shows extensive differences from those of the corresponding mammalian, fruit fly, and bacterial enzymes (52-68% residue non-identities), but also from that of another yeast, Saccharomyces cerevisiae (38%). A eubacterial type and a yeast type of glucose-6 phosphate dehydrogenase are discerned, in addition to the known mammalian type. They are distinguished from each other, from the mammalian type, and the insect enzyme, on the basis of both specific residues and pattern differences. The distribution of residues conserved in all forms locates short segments in which identities are closely grouped. Approximately 50% of these segments correspond to predicted turns and appear to mark the principal folds characteristic of the enzyme's tertiary structure. A region in the N-terminal part of the protein chain has characteristics suggestive of a coenzyme-binding site, while, in the middle third, another functionally important segment may be related to glucose-6 phosphate binding and catalysis. PMID- 8444165 TI - Dissociation of lactate dehydrogenase in aqueous and reversed micellar solutions. A time-resolved polarized fluorescence study. AB - Dissociation behavior of lactate dehydrogenase from hog muscle, both in aqueous solution and reversed micelles of sodium bis(2-ethylhexyl sulfosuccinate) in octane was studied using time-resolved polarized fluorescence spectroscopy. It was found that, in aqueous solutions, the enzyme underwent partial dissociation with the formation of isolated subunits at enzyme concentrations below 8 nM. Dissociation of the enzyme also took place upon entrapment of lactate dehydrogenase into reversed micelles under conditions of low surfactant hydration, when micelles were not large enough to accommodate a whole protein molecule. PMID- 8444166 TI - 1H-NMR investigation of oxidized and reduced high-potential iron-sulfur protein from Rhodopseudomonas globiformis. AB - 1H one-dimensional and two-dimensional NMR spectra have been recorded for the oxidized and reduced forms of the high-potential iron-sulfur protein (HiPIP) from Rhodopseudomonas globiformis which has the highest known reduction potential. The spectrum of the oxidized protein is similar to that of Chromatium vinosum and Rhodocyclus gelatinosus HiPIP but different from that of the HiPIP II from Ectothiorhodospira halophila. Surprisingly, site-specific assignment has shown that in the oxidized protein the distribution of oxidation numbers within the cluster is very similar to that found for E. halophila HiPIP II and different from that of the other two proteins. The spectrum of the reduced species is very similar to that of all other HiPIPs known to date, indicating very similar electronic and geometric structures for the reduced forms. These findings are discussed in terms of cluster structure in HiPIPs and of redox potentials. PMID- 8444167 TI - An N-terminal peptide from link protein is rapidly degraded by chondrocytes, monocytes and B cells. AB - A peptide cleaved from the link-protein component of human and pig proteoglycan aggregates by trypsin and stromelysin was taken up and degraded further by human monocytes, B cells, chondrocytes and by mouse peritoneal macrophages. Monocytes were able to process the peptide twice as rapidly as peritoneal macrophages and some 16 times more rapidly than articular chondrocytes. The B cell line Priess, which unlike the monocytes and macrophages could not take up or degrade whole proteoglycan aggregates, was able to degrade the peptide at a rapid rate. Synthetic, unglycosylated peptides consisting of the first 16 and 13 N-terminal amino acids of human link protein, corresponding to its stromelysin-cleavage and trypsin-cleavage products, were also taken up and degraded in a similar manner to the natural products and, in addition, were able to block uptake of the 125I labelled natural peptides. The isoelectric points of the re-secreted breakdown fragment from both the synthetic and natural peptides were identical and each peptide was processed by the cells to produce a single radiolabelled fragment. Each of these fragments was eluted with the same retention time during HPLC, indicating that the natural peptides were derived from the N-terminal region of the link. Since a proportion of the link protein extracted from human and pig cartilage has already undergone proteolysis to remove peptides from its N terminal region, these peptides may be produced in articular cartilage during the normal process of turnover and ageing. Although a physiological function for this protein has not been established, it may have a homeostatic role in the regulation of proteoglycan synthesis. PMID- 8444168 TI - The role of the Crabtree effect and an endogenous fuel in the energy metabolism of resting and proliferating thymocytes. AB - Rat thymocytes have been used to characterize the changes in energy metabolism that occur as cells undergo a resting/proliferation transition. In the resting state, anaerobic ATP production accounts for only 4% of ATP turnover. The remainder is fueled by the oxidation of a mixture of an unidentified endogenous fuel (62%), glucose (18%) and glutamine (16%). 48 h after mitogen stimulation, the ATP turnover has increased twofold. In these proliferating cells, glucose inhibits oxygen consumption by 58%, indicating a profound Crabtree effect which is not present in resting cells. Consequently, proliferating cells, in the presence of glucose and glutamine, fuel the majority (61%) of ATP turnover anaerobically, producing lactate from glucose. The development of a Crabtree effect may be the result of the 8-10-fold increase in glycolytic enzyme activities which occurs with proliferation. Possible advantages of such a proliferative metabolism are a sparing of endogenous fuel, and a minimizing of oxidative metabolism, with its concurrent production of free radicals. PMID- 8444169 TI - Carotenoid-binding proteins of photosystem II. AB - The distribution of the photosynthetic pigments of the chlorophyll-binding proteins or photosystem-II membranes, isolated from dark-adapted maize leaves was determined. Most (80%) of a xanthophyll, violaxanthin, was found in the three minor chlorophyll-a/b proteins CP24, CP26 and CP29 whose function is unknown. Violaxanthin is the precursor of zeaxanthin, which is involved in dissipating excess excitation energy into heat [Demmig-Adams, B. (1991) Biochim. Biophys. Acta 1020, 1-24] under conditions of high transmembrane pH gradient [Gilmore, A. M. & Yamamoto, H. Y. (1992) Proc. Natl Acad. Sci. USA 89, 1899-1903]. We propose that a role for the minor photosystem-II chlorophyll-a/b proteins is the regulation of energy transfer to the reaction centre. It was also confirmed that the photosystem II reaction centre (D1-D2-cytochrome b559) contains beta-carotene as the only carotenoid. However, the two other chlorophyll-a-binding proteins of photosystem II, CP47 and CP43, bind not only beta-carotene, but also the xanthophyll lutein, previously thought to be restricted to chlorophyll-a/b proteins. PMID- 8444170 TI - Disruption of TPS2, the gene encoding the 100-kDa subunit of the trehalose-6 phosphate synthase/phosphatase complex in Saccharomyces cerevisiae, causes accumulation of trehalose-6-phosphate and loss of trehalose-6-phosphate phosphatase activity. AB - Preparations of the trehalose-6-phosphate synthase/phosphatase complex from Saccharomyces cerevisiae contain three polypeptides with molecular masses 56, 100 and 130 kDa, respectively. Recently, we have cloned the gene for the 56-kDa subunit of this complex (TPS1) and found it to be identical with CIF1, a gene essential for growth on glucose and for the activity of trehalose-6-phosphate synthase. Peptide sequencing of the 100-kDa subunit of the trehalose-6-phosphate synthase/phosphatase complex (TPS2) revealed one sequence to be 100% identical with the deduced amino acid sequence of the upstream region of PPH3 on the right arm of chromosome IV. This sequence was used to clone an upstream region of PPH3 containing an open reading frame of 2685 nucleotides, predicted to encode a polypeptide of 102.8 kDa. The N-terminal sequence, as well as three internal amino acid sequences, obtained from peptide sequencing of the 100-kDa subunit, were identical with specific regions of the deduced amino acid sequence. Thus, the sequence cloned represents TPS2, the gene encoding the 100-kDa subunit of the trehalose-6-phosphate synthase/phosphatase complex. Interestingly, a stretch of about 500 amino acids from the first part of TPS2 was 33% identical with the entire TPS1 sequence. Disruption of TPS2 had no effect on trehalose-6-phosphate synthase activity but caused complete loss of trehalose-6-phosphate phosphatase activity, measured in vitro, and accumulation of excessive amounts of trehalose-6 phosphate instead of trehalose upon heat shock or entrance into stationary phase in vivo. These results suggest that TPS2 codes for the structural gene of the trehalose-6-phosphate phosphatase. Heat shock induced an increase in trehalose-6 phosphate phosphatase activity and this was preceded by an accumulation in TPS2 mRNA, suggesting that the trehalose-6-phosphate phosphatase is subjected to transcriptional control under heat-shock conditions. PMID- 8444171 TI - Synthetic immunogens. The effect of the conformational space on biological and immunological responses to dimeric hormone constructs. AB - Chimeras of the double chain bis-cystinyl hinge fragment 225-232/225'-232' of the human IgG1 and of peptides related to human little-gastrin were synthesized, whereby the fully bioactive gastrin sequences 2-17 and 5-17 were amide-bond linked N- and N- or C-terminally, respectively, to the hinge peptide. All the dimeric constructs proved to be efficient immunogens; however, both the configuration of the constructs and the length of the haptenic gastrin molecule were found to drastically affect the specificity of the antibody response and, thus, the type of dominant immune epitope expressed. The different degree of accessibility of the gastrin chains in the dimers is similarly reflected by their binding affinities to gastrin receptors and their bioactivities in vivo. Molecular dynamics simulations of the chimeric compounds clearly revealed that the conformational space of the gastrin peptide chains 2-17 and 5-17 is strongly restricted upon linkage to the hinge peptide. Only in the gastrin-(2-17) construct does sufficient free conformational space seem to be retained, at least for one of the two gastrin chains, in order to allow folding into the bioactive structure. This also agrees with the observation that the dimeric gastrin-(2-17) behaves like a gastrin monomer in terms of receptor binding affinity and biopotency in vivo; but it could additionally explain why an antibody response of gastrin receptor-like specificity could only be induced with this construct. The experimental data may therefore suggest a high degree of parallelism between the mechanism of recognition of the gastrin peptides in the dimeric constructs as hormonal ligands by the gastrin receptors and as haptens by the immune competent cells. PMID- 8444172 TI - Modulation of human prorenin gene expression by antisense oligonucleotides in transfected CHO cells. AB - Four phosphorothioate oligonucleotides whose sequences are complementary to the 5' untranslated region, the initiation codon or the coding region of human prorenin mRNA, were studied for their capacity to inhibit gene expression in stably transfected Chinese hamster ovary (CHO) cells constitutively producing human prorenin. In contrast to oligomers complementary to the initiation codon and the coding region, antisense oligomers directed towards the 5' untranslated region have no inhibitory effects. The intracellular delivery of a biotinylated phosphorothioate oligonucleotide (biotin-CATCCATGCTTCCCTC) was monitored in immunofluorescence studies. In the absence of a cationic liposome preparation, Lipofectin, the oligomer failed to penetrate the cells. In the presence of Lipofectin, the 35S-labelled oligomer entered the cells and was distributed in proportions of 54% to the nuclei and 35% to the cytosol. The effects of regular oligonucleotides and of 3'-end and/or 5'-end-modified phosphodiester oligonucleotides on prorenin production were tested. Terminal modification by biotinylation at the 5'-end and/or 3'-dodecyl esterification stabilized oligonucleotides towards exonucleases, but did not translate into a significant inhibition of prorenin production and did not improve the intracellular delivery and or stability of the oligomers. We have shown that it is possible to inhibit prorenin production intracellularly using specific antisense oligonucleotides. Stability and delivery are crucial factors in the design of potent and specific compounds directed at prorenin mRNA. PMID- 8444173 TI - Defective biosynthesis of the lipid A component of temperature-sensitive firA (omsA) mutant of Escherichia coli. AB - The biosynthesis of lipid A component was shown to be defective in a temperature sensitive firA mutant of Escherichia coli. Cells were biosynthetically labelled with [14C]acetate and incorporation of radioactivity into the glycerophospholipid compared to lipid A fractions was measured. The lipid A/glycerophospholipid biosynthesis ratio of the firA mutant at 37 degrees C was approximately 50%, and at the nonpermissive temperature of 42 degrees C was less than 20% of that observed in the corresponding wild-type strain. Analysis of radiolabelled lipid A 4'-monophosphate derivatives and glycerophospholipids by thin-layer chromatography revealed that the firA mutant at 42 degrees C elaborated an altered lipid A, and its phosphatidylglycerol content was low. The chemical composition of the extracted lipopolysaccharides differed significantly between the firA and the wild-type strain only in the proportion of hexadecanoic acid, which was minimal in the wild type grown at 37 degrees C and 42 degrees C and in firA lipopolysaccharide grown at 37 degrees C. In the firA mutant lipopolysaccharide produced at 42 degrees C, hexadecanoic acid was present in approximately every third molecule, attached to the hydroxyl group of the amide linked (R)-3-hydroxytetradecanoic acid at the reducing glucosamine of lipid A. Inspection of dephosphorylated free lipid A preparations by laser-desorption mass spectrometry confirmed that significant amounts of heptaacyl lipid A was elaborated by the firA strain grown at 42 degrees C. PMID- 8444174 TI - Selective eicosanoid formation during HL-60 macrophage differentiation. Regulation of thromboxane synthase. AB - Earlier studies on HL-60 cells induced to differentiate into macrophages by phorbol esters have shown a selective stimulation of thromboxane (Tx) formation from endoperoxide prostaglandin (PG) H2, indicating that Tx synthesis is regulated at the level of Tx synthase (TxS), one of the peripheral enzymes of the PGH-synthase pathway. We now report on the regulation of TxS during HL-60 macrophage differentiation using monoclonal anti-TxS serum and comparing turnover rates of TxS and its biological activity with those of other enzymes of arachidonic acid metabolism. Western-blot analysis, enzyme-linked immunosorbent assay, immunohistochemical staining and [35S]methionine-labeling experiments suggested a phorbol-ester-dependent early induction of synthesis of TxS. [35S]Methionine incorporation into TxS was stimulated within 4 h after initiation of differentiation and was associated with a major rise in the TxS catalytical activity. Pulse-chase experiments showed a half life for the TxS protein of 16.4 h in both control and phorbol-ester-treated cells. The biological half life of TxS was 10.5 h, as determined by PGH2 incorporation into TxB2 after cycloheximide treatment. In contrast, the biological half lives of PGH synthase, prostacyclin synthase and 5-lipoxygenase were significantly shorter and were 3, 2.5 and 2.5 h, respectively. These results reveal that Tx synthesis in macrophages is mediated by at least two distinct mechanisms; a protein-kinase-C-dependent induction of de novo synthesis of TxS and the selective resistance of the enzyme against the activity of protein kinase C. PMID- 8444175 TI - N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)colcemid, a probe for different classes of colchicine-binding site on tubulin. AB - The nature of binding of 7-nitrobenz-2-oxa-1,3-diazol-4-yl-colcemid (NBD colcemid), an environment-sensitive fluorescent analogue of colchicine, to tubulin was tested. This article reports the first fluorometric study where two types of binding site of a colchicine analogue on tubulin were detected. Binding of NBD-colcemid to one of these sites equilibrates slowly. NBD-colcemid competes with colchicine for this site. Binding of NBD-colcemid to this site also causes inhibition of tubulin self-assembly. In contrast, NBD-colcemid binding to the other site is characterised by rapid equilibration and lack of competition with colchicine. Nevertheless, binding to this site is highly specific for the colchicine nucleus, as alkyl-NBD analogues have no significant binding activity. Fast-reaction-kinetic studies gave 1.76 x 10(5) M-1 s-1 for the association and 0.79 s-1 for the dissociation rate constants for the binding of NBD-colcemid to the fast site of tubulin. The association rate constants for the two phases of the slow site are 444.4 M-1 s-1 and 11.67 M-1 s-1 [corrected], respectively. These two sites may be related to the two sites of colchicine reported earlier, with binding characteristics altered by the increased hydrophobic nature of NBD colcemid. PMID- 8444176 TI - Sequence-specific DNA-triplex formation at imperfect homopurine-homopyrimidine sequences within a DNA plasmid. AB - The ability of pyrimidine-rich and purine-rich oligodeoxynucleotides to form stable triple-helical structures with imperfect R.Y target sites, containing C interruptions in the purine strand (CG inversions) and located within Bluescript KS+, a plasmid of 2959 bp, has been investigated by electrophoresis, ultraviolet absorbance and cleavage-protection experiments. First, we synthesized double stranded oligonucleotides corresponding to the plasmid sites and studied their interaction with oligopyrimidines which oppose either G or T to CG inversions. The resulting imperfect DNA triplexes were detected by gel-mobility shift. Their melting profiles were found to be biphasic, and the triplex-to-duplex plus single strand transition was affected by hysteresis. The 21-nucleotide triplex containing three GC.G mismatched triads had tm = 45 degrees C, while the same triplex, but with three GC.T triads, had tm = 31 degrees C. Moreover, replacing C with 5-methylcytosine in the third strand resulted in a significant stabilization of the defective triplex, tm = 49 degrees C. The potential of the 21-nucleotide oligopyrimidines to recognize and bind in a sequence-specific manner to imperfect R.Y sequences in Bluescript KS+ has been investigated by means of a restriction endonuclease-protection assay, taking advantage of the fact that one R.Y sequence of Bluescript KS+ was partially overlapped with a HaeII site. Effective endonuclease inhibition was observed with oligopyrimidines opposing G-to-GC inversions, at 10-50 microM. By contrast, the oligopyrimidine opposing T-to-CG inversions did not exhibit any interference with endonuclease activity in our standard conditions. Finally, we have tested the ability of purine-rich strands to bind the R.Y sites of Bluescript KS+. A very weak cleavage protection was observed by using an oligomer (130 microM) with a polarity antiparallel to the purine strand of the target site. The resulting Y.R.R triplex was stabilized by CG.G (GC.G) and TA.A base triplets. This triplex denatures with a low cooperative melting profile suggesting the absence of strong interactions between the third strand and the target site. PMID- 8444177 TI - Purification and some properties of 11-hydroxythromboxane B2 dehydrogenase from porcine kidney. AB - A protein with NAD-dependent 11-hydroxythromboxane B2 dehydrogenase activity was purified to apparent homogeneity from porcine kidney using a relatively simple purification procedure, involving precipitation, anion-exchange chromatography (diethylaminoethyl-cellulose), affinity chromatography (5'-AMP-Sepharose) and gel filtration chromatography (Protein Pak 125). The dehydrogenase was found to have a molecular mass of 50-55 kDa as determined by comparison with standards on SDS/PAGE. The molecular mass on gel-filtration chromatography was dependent on the ionic strength of the buffer. The apparent Km and Vmax values for thromboxane B2 were also dependent of the ionic strength with a Vmax of 214 nmol min-1 mg-1 using 250 mM Tris/HCl, pH 8.0, and a corresponding Km of 2.9 mM. The enzyme was NAD dependent and was clearly separated from the proteins with 15 hydroxyprostaglandin dehydrogenase activity also present in the kidney. Furthermore, it was found that 11-hydroxythromboxane B2 dehydrogenase did not utilize prostaglandin D2, prostaglandin E2, prostaglandin F2 alpha or cholic acid as substrate, and that the enzyme did not catalyse the reverse reaction, conversion of 11-dehydrothromboxane B2 to thromboxane B2. PMID- 8444178 TI - Glycerophosphocholine release in human erythrocytes. 1H spin-echo and 31P-NMR evidence for lysophospholipase. AB - The direct techniques of 1H spin-echo and 31P-NMR spectroscopy made it possible to monitor the release of glycerophosphocholine from lysophosphatidylcholine in lysates from human red blood cells. Thus, the existence of a lysophospholipase in human erythrocytes was confirmed using a new more direct method. No evidence for a phospholipase A2 activity in the haemolysates was found with the same approach; since this enzyme is present in leukocytes, the absence of activity helped verify the purity of the erythrocyte preparation. The lysophospholipase may constitute, with the earlier described glycerophosphocholine phosphodiesterase activity, a metabolic unit for the removal of haemolytic lysophosphatidylcholine which is formed in the erythrocyte membranes as well as taken up from the plasma. PMID- 8444179 TI - In vitro pore-forming activity of the lantibiotic nisin. Role of protonmotive force and lipid composition. AB - Nisin is a lantibiotic produced by some strains of Lactococcus lactis subsp. lactis. The target for nisin action is the cytoplasmic membrane of Gram-positive bacteria. Nisin dissipates the membrane potential (delta psi) and induces efflux of low-molecular-mass compounds. Evidence has been presented that a delta psi is needed for nisin action. The in vitro action of nisin was studied on liposomes loaded with the fluorophore carboxyfluorescein. Nisin-induced efflux of carboxyfluorescein was observed in the absence of a delta psi from liposomes composed of Escherichia coli lipids or dioleoylglycerophosphocholine (Ole2GroPCho) at low nisin/lipid ratios. The initial rate of carboxyfluorescein efflux is dependent on the nisin/lipid ratio and saturates at high ratios. Both delta psi (inside negative) and delta pH (inside alkaline) enhance the action of nisin, while nisin is more potent at acidic external pH values. Efficient carboxyfluorescein efflux is observed with the zwitterionic phospholipid Ole2GroPCho or mixtures of Ole2GroPCho with dioleoylglycerophosphoethanolamine and neutral glycolipids, while anionic phospholipids are strongly inhibitory. It is concluded that a delta psi is not essential, but that the total protonmotive force stimulates the action of nisin. PMID- 8444180 TI - Cloning, sequencing, and expression of Trypanosoma brucei dihydrolipoamide dehydrogenase. AB - A gene encoding dihydrolipoamide dehydrogenase was isolated from Trypanosoma brucei genomic DNA by using a combination of polymerase chain reaction and screening of a lambda EMBL3 library. The DNA sequence reveals that it encodes a protein of 478 amino acids (M(r) 49935) highly similar to previously sequenced dihydrolipoamide dehydrogenases. The gene was ligated into pMEX8 and expressed in an Escherichia coli mutant that lacks dihydrolipoamide dehydrogenase. Expression resulted in the appearance of dihydrolipoamide dehydrogenase activity concurrent with the production of a protein of the expected M(r) as determined by SDS/PAGE and Western blotting. PMID- 8444181 TI - Purification and characterization of anthranilate synthase from Catharanthus roseus. AB - Anthranilate synthase (EC 4.1.3.27) has been purified from cell cultures of Catharanthus roseus by poly(ethylene glycol) precipitation/fractionation and subsequent separation by anion exchange on Q-Sepharose, Orange A dye chromatography, Mono Q anion-exchange chromatography and Superose 6 gel filtration. By analogy to anthranilate synthases from other sources it does look like the enzyme is a tetramer composed of two large and two small subunits, with molecular mass 67 and 25.5 +/- 0.5 kDa, respectively. The molecular mass determined by gel filtration was 143 +/- 5 kDa. The enzyme had a pI of 5.1 determined by chromatofocusing. The pH optimum was between pH 7.5 and pH 8.3, but the type of buffer used affected the results. The enzyme could utilize NH4+ as ammonium donor instead of glutamine. The enzyme showed normal Michaelis-Menten kinetics with respect to the substrates L-glutamine and chorismate, and the cofactor Mg2+, Km values for L-glutamine was determined to be 0.37 +/- 0.05 mM, for chorismate 67 +/- 3 microM, and for MgCl2 0.26 +/- 0.03 mM respectively. Anthranilate synthase was inhibited by L-tryptophan, tryptamine and D-tryptophan (with L-tryptophan being the best inhibitor). The enzyme was allosterically regulated showing positive cooperatively of chorismate binding at higher concentrations of tryptophan. For a tryptophan concentration of 20 microM the Hill coefficient was determined to be 2. The tryptophan binding sites showed positive cooperatively for higher concentrations of chorismate. The purified enzyme did not contain anthranilate-5-phosphoribosylpyrophosphate phosphoribosyltransferase activity and is thus not of the same type as the well characterized Salmonella typhimurium anthranilate synthase/phosphoribosyl pyrophosphate transferase bifunctional type. PMID- 8444182 TI - Production of recombinant notechis 11'2L, an enzymatically active mutant of a phospholipase A2 from Notechis scutatus scutatus venom, as directly generated by cleavage of a fusion protein produced in Escherichia coli. AB - We have constructed an expression vector to produce, in Escherichia coli, a fusion protein containing successively two IgG binding domains from staphyloccocal protein A, a nine-amino-acid linker peptide terminating in a methionine residue and the phospholipase A2 notechis 11'2L, an isoform of notexin of Notechis scutatus scutatus venom. Notechis 11'2L is a mutant of the naturally occurring notechis 11'2 [Bouchier, C., Boyot, P., Tesson, F., Tremeau, O., Bouet, F., Hodgson, D., Boulain, J. C. & Menez, A. (1991) Eur. J. Biochem. 202, 493-500] in which Met8 has been replaced by Leu. The fusion protein was recovered in the periplasmic extract with a yield of 0.25 mg/l culture. It was hydrolyzed with cyanogen bromide, yielding a protein having the molecular mass, amino acid composition and N-terminal sequence of notechis 11'2L. Notechis 11'2L and the wild notechis 11'2 displayed identical circular dichroic spectra and shared similar enzymatic, myotoxic and antigenic properties, suggesting that the recombinant notechis 11'2L was directly generated in a correctly folded form. PMID- 8444183 TI - Dissecting the contributions of a specific side-chain interaction to folding and catalysis of Bacillus stearothermophilus lactate dehydrogenase. AB - X-ray crystallography predicts hydrogen-bonding interactions between the side chains of Thr198 and two other amino acid residues, Glu194 (adjacent to the catalytic His195) and Ser318 (on the alpha-H helix which rearranges on substrate binding). In order to investigate the contribution of this conserved amino acid residue, Thr198, two mutants of Bacillus stearothermophilus lactate dehydrogenase were created (Val198 and Ile198). The steady-state kinetic parameters for both mutant enzymes were very similar with increased substrate Km and reduced kcat when compared with the wild-type enzyme. The mutation Val198 allowed non productive binding of pyruvate to the unprotonated form of His195. Steady-state kinetic parameters determined for the Val198 mutant enzyme in high solvent viscosity suggested both an altered rate-limiting step in catalysis and implicated Thr198 in allosteric activation by the effector fructose 1,6 bisphosphate (Fru1,6P2). A shift in the Fru1,6P2 activation constant for the Val198 mutant enzyme suggested that Thr198 stabilises the catalytically competent (Fru1,6P2-activated) form of the enzyme by 6.6 kJ/mol. However, Thr198 was not important for maintaining the thermal stability of the Fru1,6P2-activated form. Equilibrium unfolding in guanidinium chloride indicated that Thr198 contributes 17.2 kJ/mol subunits towards the tertiary structural stability. The results emphasise the importance of the side chain-hydroxyl group of Thr198 which is required for (a) productive substrate binding, (b) allosteric activation and (c) protein conformational stability. The characteristics of the B. stearothermophilus lactate dehydrogenase mutations reported here were significantly different from those of the same mutations made in the corresponding position of the analogous enzyme Thermus flavus malate dehydrogenase [Nishiyama, M., Shimada, K., Horinouchi, S., & Beppu, T. (1991) J. Biol. Chem. 266, 14294-14299]. PMID- 8444184 TI - Are the tryptophanyl-tRNA synthetase and the peptide-chain-release factor from higher eukaryotes one and the same protein? AB - Recently, cDNA clones encoding the bovine (b) [M. Garret, B. Pajot, V. Trezeguet, J. Labouesse, M. Merle, J.-C. Gandar, J.-P. Benedetto, M.-L. Sallafranque, J. Alterio, M. Gueguen, C. Sarger, B. Labouesse and J. Bonnet (1991) Biochemistry 30, 7809-7817] and human (h) [L. Yu. Frolova, M. A. Sudomoina, A. Yu. Grigorieva, O. L. Zinovieva and L. L. Kisselev (1991) Gene 109, 291-296] tryptophanyl-tRNA synthetases (TrpRS) were sequenced; the deduced amino acid sequences exhibit typical structural features of class I aminoacyl-tRNA synthetases [G. Eriani, M. Delarue, O. Poch, J. Gangloff and D. Moras (1990) Nature 237, 203-206] and limited, although significant, similarity with bacterial TrpRS. Independently, it was shown that a major protein whose synthesis is stimulated in human cell cultures by interferon gamma [J. Fleckner, H. H. Rasmussen and J. Justesen (1991) Proc. Natl Acad. Sci. USA 88, 11,520-11,524], and interferons gamma or alpha [B. Y. Rubins, S. L. Anderson, L. Xing, R. J. Powell and W. P. Tate (1991) J. Biol. Chem. 226, 24,245-24,248], exhibits TrpRS activity and an amino acid sequence identical to that of hTrpRS. The amino acid sequences of bTrpRS and hTrpRS are highly similar and are surprisingly very similar to the amino acid sequence deduced from a cloned and sequenced cDNA reported to encode rabbit (r) peptide chain-release factor (RF) [C. C. Lee, W. J. Craigen, D. M. Muzny, E. Harlow and C. T. Caskey (1990) Proc. Natl Acad. Sci. USA 87, 3508-3512]. This close similarity between mammalian TrpRS and cloned RF is unexpected given the distinct functional properties of these proteins. Consequently, the question arises as to whether the mammalian TrpRS and RF activities reside on identical or very similar polypeptides. Alternatively, one may assume that the cloned rabbit cDNA encodes a protein other than rRF. Several properties (immunochemical, biochemical and physico-chemical) of mammalian TrpRS and RF have been compared. rTrpRS and rRF have distinct thermostability behaviours, and dissimilar chromatographic profiles on phosphocellulose. Both the anti-bTrpRS polyclonal antibodies and the monoclonal antibody Am2 strongly inhibit the bTrpRS and hTrpRS aminoacylation activities, but not the rRF activity. In addition, neither bTrpRS nor hTrpRS exhibit RF activity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8444185 TI - Epidermal-growth-factor receptors generate Ras.GTP more efficiently than insulin receptors. AB - Activation of the Ras proto-oncogene contributes in general to mitogenic activation of cells. We show here that epidermal growth factor (EGF) stimulates Ras.GTP formation very efficiently in a variety of cell lines expressing endogenous EGF receptors only. Maximal activation of the receptor converts up to 65% of cellular p21ras from the GDP form into the active GTP-bound state. This efficient activation occurs also in cultured primary human fibroblasts. Maximal insulin-induced Ras.GTP formation is less but in cells overexpressing the insulin receptor a similar high response of Ras.GTP formation is observed after insulin stimulation. Not only the efficiency but also the kinetics by which the EGF and insulin receptors stimulate Ras.GTP formation are quite distinct. In the Rat-1 derived cell line, H13IR2000, overexpressing both p21Ha-ras and the insulin receptor, the activated insulin receptor generates approximately 1 mol Ras.GTP/mol activated insulin receptor. The activated EGF receptor amplifies the signal, resulting in the activation of approximately 40 mol p21ras/mol receptor. Moreover, EGF-stimulated generation of Ras.GTP is transient with a maximum after 2 min of hormone stimulation and diminishes to near basal levels within 1 h whereas the insulin-induced Ras.GTP levels are maximal at 5-10 min and decline only slowly to half-maximal in 1 h. Desensitization of the EGF pathway by prolonged EGF stimulation, prevents subsequent stimulation of Ras.GTP formation by newly added EGF but not by insulin. Vice versa, in cells preincubated with insulin for 1 h, EGF stimulates Ras.GTP formation to near maximal values. These observations indicate that desensitization by prolonged hormone incubation does not involve inactivation of common signaling intermediates but rather components, specific for each pathway, like the particular receptors. The rapid down regulation of EGF receptors compared to insulin receptors corroborate this possibility. The observed high potency of EGF receptors to generate Ras.GTP may explain the, in general, stronger mitogenic activity of EGF compared to insulin. PMID- 8444186 TI - Complete primary structure of chicken collagen XIV. AB - We have isolated and characterized several overlapping cDNA clones for chicken collagen XIV which span a total of 6.5 kpb. These clones contain an open reading frame of 5571 bp encoding the entire collagen XIV polypeptide. The predicted polypeptide has an estimated molecular mass of 205 kDa in its glycosylated form. It is composed of 1857 amino acids which are arranged in 16 individual subdomains, including a signal peptide of 28 residues. The large amino-terminal globular domain of collagen XIV (NC3) comprises 11 of these 16 subdomains. Two of them are related to the A modules of von Willebrand factor, eight show some relationship to the type III-repeats of fibronectin and one is similar to the NC4 domain of collagen IX. The carboxy-terminal triple-helical domain is composed of two collagenous segments (COL1 and COL2), which make up less than 14% of the entire molecular mass, and of two short non-collagenous domains (NC1 and NC2). A detailed analysis of our cDNA clones indicates that collagen XIV exists in two alternatively spliced forms which differ by 31 amino acids in their NC1 domain. The variant form of the polypeptide contains 1888 amino acids with a total molecular mass of 208 kDa. Our results demonstrate that collagen XIV displays a complex multidomain structure resembling that proposed for collagen XII. PMID- 8444187 TI - Tumor necrosis factor cytotoxicity is associated with phospholipase D activation. AB - The activation of phospholipase D in different cell lines treated with recombinant human tumor necrosis factor (TNF) has been investigated. When the murine fibrosarcoma cell lines L929 and WEHI164c113, as well as the human promonocytic cell line U937, were prelabeled with [14C]palmitic acid or [3H]arachidonic acid, and treated with TNF in the presence of ethanol, TNF induced the synthesis of [14C]phosphatidylethanol or [3H]phosphatidylethanol, respectively, as the result of a phospholipase-D-catalyzed transphosphatidylation. TNF-induced phospholipase D activity was observed 1 h before the onset of cell killing and gradually increased thereafter. Subclones selected for resistance to TNF cytotoxicity did not show phospholipase D activation in response to TNF. In contrast, when these subclones were treated with TNF in the presence of actinomycin D, TNF cytotoxicity as well as TNF induced phospholipase D activity could be restored. TNF cytotoxicity and TNF induced phospholipase D activity were equally modulated by various drugs known to interfere with different steps in the TNF-signaling pathway. Phospholipase D activation was found not to be the result of cell killing per se, as a number of other cytotoxic reagents were unable to activate phospholipase D. Prelabeling of cells with [14C]lysophosphatidylcholine indicated phosphatidylcholine as one of the substrates for TNF-activated phospholipase D. In conclusion, this study demonstrates that TNF-induced cytotoxicity is associated with activation of phospholipase D. PMID- 8444188 TI - Purification and phosphorylation of elongation factor-2 kinase from rabbit reticulocytes. AB - Eukaryotic elongation-factor-2 kinase has been purified to homogeneity from rabbit reticulocytes through a seven-step procedure and has been identified as a protein with a molecular mass of approximately 103 kDa as judged by SDS/PAGE. A degradation product of about 95 kDa was also evident in some preparations. The activity of the purified kinase was completely dependent on calcium and calmodulin. The kinase rapidly underwent extensive autophosphorylation, incorporating 1 mol phosphate/mol within 1 min; 5 mol phosphate/mol were incorporated within 1 h. The autophosphorylation was Ca2+/calmodulin-dependent; phosphopeptide mapping revealed multiple phosphopeptides even after just 0.5 min of autophosphorylation, suggesting that a number of sites became rapidly phosphorylated. Autophosphorylation occurred on serine and threonine residues. Preincubation in the presence of Ca2+, Mg2+ and ATP produced a rapid 2-3-fold activation of the kinase and also induced partial Ca(2+)-independent activity. Preincubation in the absence of the ligands showed that all three were required for full activation and induction of Ca(2+)-independent activity. PMID- 8444189 TI - Cloning and expression of Saccharomyces cerevisiae copper-metallothionein gene in Escherichia coli and characterization of the recombinant protein. AB - The gene sequences for intact and truncated forms of copper-binding metallothionein from Saccharomyces cerevisiae were cloned and overexpressed in Escherichia coli BL21(DE3)pLysE cells. In contrast to several other genes, the intact and truncated metallothionein genes are amplified in the polymerase chain reaction when Mg2+ is replaced by Co2+. The recombinant truncated protein binds copper in vivo and in vitro. A ratio of 8 Cu/12 cysteines was determined from atomic absorption, X-ray fluorescence and amino acid analysis. Extended X-ray absorption spectroscopy indicates that all Cu is in Cu(I) form and coordinated to three S atoms. PMID- 8444190 TI - Study of the states and populations of the rat pancreatic cholecystokinin receptor using the full peptide antagonist JMV 179. AB - The full peptide antagonist of the pancreatic cholecystokinin (CCK) receptor, JMV 179, [Boc-Tyr(SO3H)-Ahx-Gly-dTrp-Ahx-Asp phenylethyl ester, where Tyr(SO3H) = sulfated tyrosine, Ahx = 6-aminohexanoic acid] was modified at its N-terminus by incorporation of p-hydroxyphenyl propionate (Bolton-Hunter reagent, BH) and was subsequently radioiodinated. After HPLC purification, 125I-BH-JMV-179, a CCK antagonist radioligand of high specific activity (2000 Ci/mmol) was obtained. 125I-BH-JMV-179 bound to a single population of sites on rat pancreatic plasma membranes, (Kd = 3.9 nM, Bmax = 40 pmol/mg protein). Binding was dependent on time, temperature, and protein concentration, and was fully reversible. JMV 179 radioligand detected four times as many sites as an agonist radioligand [C. Hadjiivanova, M. Dufresne, S. Poirot, P. Sozzani, N. Vaysse, L. Moroder and D. Fourmy (1992) Eur. J. Biochem. 204, 273-279]. Agonists and antagonists of the A- and B-subtype CCK/gastrin receptors inhibited 125I-BH-JMV-179 binding with an order of potency compatible with the A-subtype CCK receptor pharmacology. Moreover, the sulfate group on the tyrosine residue of the CCK peptides appeared to be of much less importance for antagonist affinity than for agonist affinity. Inhibition of 125I-BH-JMV-179 binding by agonists (except JMV 180), demonstrated the presence of two affinity classes of binding sites. The population of sites having an apparent high affinity for CCK represented 30 pmol/mg protein and threefold the number of high-affinity sites previously identified by an agonist radioligand. In presence of non-hydrolyzable GTP, all the sites bound CCK agonists with a low affinity. Moreover, saturation analysis of JMV 179 radioligand binding in the presence of CCK indicated that CCK interacted competitively with all JMV 179 sites and demonstrated binding of JMV 179 radioligand to two distinct affinity classes of sites. In the presence of GTP[S] a single affinity class of sites for JMV 179 radioligand was found as in the control experiments without CCK. This study, with the first CCK peptide antagonist radioligand, demonstrates that CCK receptors exist in two interconvertible affinity states regulated by guanine-nucleotide-binding regulatory protein(s) in rat pancreatic plasma membranes. JMV 179 radioligand does not induce receptor coupling but distinguishes the two affinity states of the CCK receptors. JMV 179 reveals the existence of populations of high-affinity and low-affinity sites for CCK which had not previously been detected by agonist radioligand binding, thus suggesting heterogeneity of CCK receptor sites in membranes. PMID- 8444191 TI - The 0.25-nm X-ray structure of the Bowman-Birk-type inhibitor from mung bean in ternary complex with porcine trypsin. AB - The structure of the Bowman-Birk-type inhibitor from mung bean Phaseolus aureus has been determined in ternary complex with porcine trypsin. The complex formed crystals of the trigonal space group P3(1)21 which diffracted to a resolution of 250 pm. Each of the two mung bean protease reactive sites is bound to trypsin according to the standard mechanism for serine proteinase inhibition. The binding loops thereby adopt the canonical conformation for the standard mechanism; however, the sub-van der Waals contact between the active-site serine O gamma (195) and the P1 carbonyl carbon of both loops is significantly smaller (210 pm) than hitherto observed, with continuous electron density connecting the two atoms. The inhibitor is formed by two double-stranded antiparallel beta-sheets, which are connected into a moderately twisted beta-sheet by a network of hydrogen bonds involving main-chain atoms and two water molecules. All contacts with neighbors in the crystal lattice occur between trypsin molecules. This apparently gives rise to an unusual form of disorder where the complexes pack in two orientations Ta:MaMb:Tb and Tb:MbMa:Ta (Ta, Tb = trypsin, Ma = mung bean loop I, Mb = mung bean loop II), such that the asymmetric unit consists of the ternary complex in two orientations, each with half occupancy. This is nearly equivalent to an asymmetric unit which has one trypsin molecule with full occupancy and one mung bean inhibitor with half occupancy and a crystallographic twofold symmetry axis through its center. Because of the approximate twofold symmetry of the inhibitor itself, however, the electron density was interpretable for most of the inhibitor (17 residues at the termini were not resolved) and shows evidence of its double orientation. PMID- 8444192 TI - Expression and purification of a trefoil peptide motif in a beta-galactosidase fusion protein and its use to search for trefoil-binding sites. AB - The cysteine-rich trefoil motif of rat intestinal trefoil factor (rITF) was cloned and expressed in Escherichia coli. A 270-bp cDNA fragment including the signal sequence and the trefoil motif was cloned into the expression vector pAX5+ to direct the expression of a beta-galactosidase collagen-hinged fusion protein in E. coli. Cultures harbouring the recombinant plasmid produced a soluble novel protein with a molecular mass of 134.5 kDa, as predicted for the trefoil-motif containing fusion protein. Purification of the rITF moiety was achieved by p aminophenyl-thio-beta-D-galactoside(APTG)-affinity chromatography, collagenase digestion of the hybrid molecule, and removal of the beta-galactosidase-hinge molecule by a further APTG-affinity step. It was demonstrated that intrachain disulphide-bond formation in rITF occurred during the procedure, so no refolding steps were required. Analysis by immunoblotting revealed that the fusion protein and the cleaved trefoil-motif-containing protein were recognised by an antibody raised against the chemically synthesised peptide. The trefoil motif present in the fusion protein was used to localise putative trefoil-binding sites in sections of frozen rat tissue. Binding was demonstrated using the beta galactosidase portion of the fusion protein as a reporter moiety, either directly with 5-bromo-4-chloro-3-indolyl-beta-D-galactoside, or indirectly using a monoclonal antibody to beta-galactosidase and indirect immunohistochemistry. Binding sites were localised to the foveolar and surface epithelium of rat stomach, the collecting ducts of the kidney and within colonic crypts. The presence of a trefoil motif was necessary for binding. The use of beta galactosidase fusion proteins for histochemical localisation of peptide-binding sites should prove more generally useful. PMID- 8444193 TI - Acceleration of bovine neurofilament L assembly by deprivation of acidic tail domain. AB - Functions of the tail region of neurofilament L have, to date, not been clearly elucidated. Bovine neurofilament L was cleaved into tail-less neurofilament L (50 kDa) and a tail fragment (19 kDa), by thrombin. Tail-less neurofilament L was deficit of the highly acidic domain of the tail region (approximately 77% of the entire region). Assembly of tail-less neurofilament L. was observed to be accelerated by both fluorometric and centrifugal measurements, compared with intact neurofilament L. The critical concentration of tail-less neurofilament L, which constitutes the constant unassembled pool, was approximately 0.25-times lower than that of neurofilament L. Under physiological conditions, tail-less neurofilament L formed a ribbon-like structure, whereas tail-less neurofilament L could form 10-nm filaments in an extremely low ionic-strength buffer in the presence of 1 mM MgCl2. An affinity-purified antibody directed against the tail fragment also accelerated neurofilament L assembly. The tail fragment neither coassembled with neurofilament L nor affect neurofilament L assembly. The acidic domain of the tail region may regulate neurofilament assembly and may be involved in 10-nm filament formation under physiological conditions. PMID- 8444194 TI - Identification of insulin-stimulated protein kinase-1 as the rabbit equivalent of rskmo-2. Identification of two threonines phosphorylated during activation by mitogen-activated protein kinase. AB - An improved procedure has been developed for the isolation of insulin-stimulated protein kinase-1 (ISPK-1), an S6 kinase-II homologue, by which 0.5 mg highly purified enzyme can be obtained within four days. The sequences of tryptic peptides from ISPK-1 (100 residues) revealed 100% identity with the predicted protein product of rskmo-2, a cDNA clone isolated from a mouse F2 cell line library [Alcorta, D. A., Crews, C. M., Sweet, L. J., Bankston, L., Jones, S. W. and Erikson, R. L. (1989) Mol. Cell. Biol. 9, 3850-3859], demonstrating that rskmo-2 encodes an S6 kinase-II. Two isoforms of mitogen-activated protein (MAP) kinase (p42mapk and p44mapk) were the only ISPK-1-reactivating enzymes detected after Mono Q chromatography of extracts prepared from rabbit skeletal muscle or phaeochromocytoma 12 cells stimulated by nerve or epidermal growth factors. One of the residues on ISPK-1 phosphorylated by p42mapk was a threonine located nine residues N-terminal to the conserved Ala-Pro-Glu motif in the C-terminal protein kinase domain, an analogous location to phosphorylation sites essential for the activity of cAMP-dependent protein kinase, MAP kinase and p34cdc2. A further threonine located five residues N-terminal to the same Ala-Pro-Glu motif was also phosphorylated, probably via autophosphorylation catalysed by ISPK-1 itself. PMID- 8444195 TI - Regulation of HSP70 gene expression during the life cycle of the parasitic helminth Schistosoma mansoni. AB - Analyses of RNA from different developmental stages of Schistosoma mansoni showed stage-specific expression of heat-shock protein 70 (hsp70), which is regulated by a developmental program and by stress. The developmental program, common to hsp70 and other genes (e.g. paramyosin), refers to constitutive expression in miracidia sporocyst and adult worm but not in cercariae, and to the termination of hsp70 gene transcription during sporocyst/cercaria transformation. Stress induction, specific to hsp70, refers to transient accumulation of high levels of hsp70 mRNA during cercariae/schistosomula transformation and in adult worms after heat shock (42 degrees C). Cercariae/schistosomula transformation can be visualized as a physiological stress involving shifts in temperature (23-37 degrees C) and in salt concentration (from water to isotonic medium), as well as removal of tails from cercariae to yield isolated bodies that transform into schistosomula. It was found that temperature is an important factor, but not sufficient for strong induction of the hsp70 genes of schistosomula. Tail removal is an obligatory step for full induction of the hsp70 genes of schistosomula, in response to a temperature shift from 23-37 degrees C. The hsp70 genes in cercariae and isolated tails do not respond to stimuli (salt and temperature increases) that strongly activate the genes in isolated bodies (i.e., schistosomula). We speculate that the hsp70 genes in intact cercariae are not inducible because the tails can produce inhibitory signals that diffuse to the bodies and suppress their hsp70 genes. This hypothesis is useful to explain the termination of hsp70 gene transcription during sporocyst/cercaria transformation by the inhibitory effect of the growing tail. PMID- 8444196 TI - Molecular cloning of a 12-lipoxygenase cDNA from rat brain. AB - A cDNA encoding an arachidonate 12-lipoxygenase from rat brain was obtained by polymerase chain reaction cloning. Primers specific for porcine leukocyte 12 lipoxygenase cDNA were used to isolate the initial polymerase-chain-reaction product (395 bp). The final sequence of the rat 12-lipoxygenase cDNA coding region (1989 bp) was verified by analysis of several separate polymerase-chain reaction products. The open reading frame corresponded to a protein of 662 amino acid residues, with a calculated molecular mass of 75,305 Da. Also the rat 12 lipoxygenase contained the six conserved histidines, characteristic for all cloned lipoxygenases. It displayed the highest degree of identity to porcine leukocyte 12-lipoxygenase (71%) and to human 15-lipoxygenase (75%), with less resemblance to human platelet 12-lipoxygenase (59%) or rat leukocyte 5 lipoxygenase (41%). The recombinant enzyme was expressed in Escherichia coli and incubated with arachidonic acid. Primarily 12-lipoxygenase (but also some 15 lipoxygenase) enzyme activity was obtained. A part of the brain 12-lipoxygenase cDNA was used as probe in Northern blots. A 2.7-kb mRNA was more abundant in RNA from rat leukocytes, lung, and aorta, than in RNA from rat brain. Sequencing of parts of the corresponding cDNAs (from leukocytes and lung), and comparison to the brain 12-lipoxygenase sequence, indicated that these mRNAs from the different rat tissues were identical. PMID- 8444197 TI - The pioneers of pediatric medicine. Johann Bokai Snr. (1822-1884). PMID- 8444198 TI - Precocious puberty due to a lipid-cell tumour of the ovary. AB - A 4-year-old girl with a lipid cell tumour of the ovary showed isosexual precocious pseudopuberty. The endocrine activity of the tumour led to elevated plasma levels of dehydroepiandrosterone sulphate, oestradiol, testosterone and androstenedione. After tumour resection the clinical signs of abnormal hormonal stimulation disappeared within 10 months. The girl developed precocious puberty again 2 years later without any sign of relapse. Therapy with luteinizing hormone releasing hormone agonist was effective although premature activation of the hypothalamic-pituitary-gonadal axis could not clearly be demonstrated by hormonal investigations. PMID- 8444199 TI - The effects of illness on sleep behaviour in infants. AB - For the purpose of evaluating the association between health problems and sleep disturbances as part of a community survey of sleep patterns in childhood, a questionnaire was administered to 752 mothers of children between the ages of 4 months and 4 years, and to the nurses at their regular baby clinics. The questionnaire covered the areas of past and present sleep and settling behaviour, as well as health history and demographic data. The study group consisted of 66 (8.9%) children who had either chronic medical problems, or history of an illness requiring hospitalisation. Regular night waking was reported in 35% and 34% of the group with and without history of illness, respectively. The mean number of interrupted nights per week was similar in both groups and so were the sleep problems perceived by the mothers. We conclude that in this age group the results do not support an association between health problems and prolonged sleep disturbances. PMID- 8444200 TI - Chylothorax in the neonatal period. AB - Chylothorax is defined as an effusion of lymph in the pleural cavity. In the neonate both congenital and traumatic (iatrogenic) forms exist. Birth asphyxia and respiratory insufficiency are major symptoms of congenital chylothorax, requiring resuscitation and artificial ventilation. Antenatal diagnosis by ultrasound allows early therapeutic intervention such as ventilatory support and drainage of chylous fluid immediately after birth. Traumatic chylothorax is mainly seen after intrathoracic surgery. Treatment primarily consists of continuous or intermittent drainage of chyle with replacement of fluid-, electrolyte-, and protein losses and parenteral nutrition. Introduction of oral feeding is considered only after a substantial period without chyle production in the pleural cavity and consists of a medium-chain triglyceride containing formula. In a minority of cases surgical intervention is necessary. PMID- 8444201 TI - Hodgkin disease in Iranian children. AB - The epidemiological pattern of Hodgkin disease (HD) was studied in 139 Iranian children with an age range of 2.5-15 years (mean age 8.3) over a 17-year period (1972-1989). The main features observed were: a high male to female ratio of 3.2:1, a high frequency of HD in toddlers and young school children (73%), the prevalence of mixed cellularity subtype (74.5%) and rare occurrence of lymphocyte depletion subtype (2%) the high occurrence of constitutional symptoms (57%) and the high rate of stage III and IV patients (73.5%). Response to the treatment consisting mainly of chemotherapy and/or radiotherapy was favourable and overall and disease-free survival rates of 91.4% and 74.2% were achieved over a follow up period of 6 months-17 years. According to these findings the epidemiological pattern of Iranian children with HD is similar to that occurring in rural areas of developed countries. PMID- 8444203 TI - Lymphocyte production of gamma-interferon as a test for non-tuberculous mycobacterial lymphadenitis in childhood. AB - Infection with Mycobacterium avium, M. intracellulare and M. scrofulaceum (MAIS) organisms in normal children may result in cervical lymphadenopathy. There is a poor response to anti-tuberculous therapy and surgical excision of infected nodes is necessary. The diagnosis therefore requires consideration in children with cervical lymphadenopathy. A simple in vitro assay is described which may be useful for diagnosis prior to excision. Whole blood is cultured with M. avium purified protein derivative. After 24 h the plasma is removed and the concentration of gamma interferon (IFN-gamma) quantified by a radioimmunometric assay. In a prospective study of 38 children with neck lesions, 16 showed MAIS organisms isolated from cultures of excised tissue. The level of IFN-gamma produced by peripheral blood lymphocytes from children in the MAIS group was significantly greater when compared with children having operations for neck lesions that were not due to MAIS organisms (P < 0.001). PMID- 8444202 TI - Aetiology of community-acquired pneumonia in children treated in hospital. AB - Viral and bacterial antigen and antibody assays were prospectively applied to study the microbial aetiology of community-acquired pneumonia in 195 hospitalised children during a surveillance period of 12 months. A viral infection alone was indicated in 37 (19%), a bacterial infection alone in 30 (15%) and a mixed viral bacterial infection in 32 (16%) patients. Thus, 46% of the 69 patients with viral infection and 52% of the 62 patients with bacterial infection had a mixed viral and bacterial aetiology. Respiratory syncytial virus (RSV) was identified in 52 patients and Streptococcus pneumoniae in 41 patients. The next common agents in order were non-classified Haemophilus influenzae (17 cases), adenoviruses (10 cases) and Chlamydia species (8 cases). The diagnosis of an RSV infection was based on detecting viral antigen in nasopharyngeal secretions in 79% of the cases. Pneumococcal infections were in most cases identified by antibody assays; in 39% they were indicated by demonstrating pneumococcal antigen in acute phase serum. An alveolar infiltrate was present in 53 (27%) and an interstitial infiltrate in 108 (55%) of the 195 patients. The remaining 34 patients had probable pneumonia. C-reactive protein (CRP), erythrocyte sedimentation rate and total white blood cell count were elevated in 25%, 40% and 36% of the patients, respectively. CRP was more often elevated in patients with bacterial infection alone than in those with viral or mixed viral-bacterial infections. No other correlation was seen between the radiological or laboratory findings and serologically identified viral, bacterial or mixed viral-bacterial infections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444204 TI - Long-term outcome in 134 patients with galactosaemia. AB - In a retrospective study 134 galactosaemic patients, born between 1955 and 1989 in the Federal Republic of Germany were traced and their long-term outcome evaluated. We investigated 83 galactosaemic patients (78 homozygotes, 5 compound heterozygotes) by clinical, psychometric and laboratory testing; 31 patients were evaluated by medical history, the remaining 20 patients had died due to sequelae of the underlying disease. In 48 out of 78 classical galactosaemia patients galactose-free therapy had been started before the 15th day, in 19 between days 15 and 56 and in 11 patients after the 56th day. Physical findings revealed that puberty was delayed in 1 out of 18 males and 6 out of 11 females. Neurological abnormalities included ataxia (n = 6), intention tremor (n = 11) and microcephaly (n = 10). Speech abnormalities were found in 43 out of 66 patients over 3 years of age and disturbance of visual perception and/or arithmetic deficits in 29. Intelligence declined with age, i.e., a DQ or IQ less than 85 was found in 4 out of 34 patients less than 6 years of age (12%), in 10 out of 18 between 7 and 12 years (56%) and in 20 out of 24 older than 12 years (83%). Metabolite patterns (RBC galactose-1-phosphate and UDP-galactose, plasma and urinary galactitol) did not correlate with DQ or IQ. Dietary compliance was good in almost all patients. Compound heterozygotes (n = 5) had normal mental and growth development and all laboratory parameters were in the normal range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444205 TI - Randomised controlled trial of weaning by patient triggered ventilation or conventional ventilation. AB - A group of preterm infants (n = 40) were entered into a randomised controlled trial to compare the duration and efficacy of weaning by patient triggered ventilation (PTV) or conventional ventilation. Once recovery from respiratory distress had begun, enabling the ventilator rate to be reduced to 40 breaths/min, infants were randomised to either regime. Infants randomised to PTV were weaned by reduction in ventilator pressure only, whereas infants randomised to conventional ventilation were weaned by reduction in ventilator rate only. Only one infant required re-ventilation within 24 h of extubation; this infant had been weaned by conventional ventilation. Three infants, all of less than 28 weeks gestation, did not tolerate weaning by PTV and were subsequently weaned conventionally. The duration of weaning was analysed according to the original randomisation allocation and was significantly shorter in the PTV group, being a median of 30 h (mean 39, range 3-186) compared to a median of 61 h (mean 65, range 15-262) in the conventional group, P < 0.02. We conclude PTV is the more advantageous form of weaning in preterm infants of greater than 27 weeks gestational age. PMID- 8444206 TI - Mild prematurity and respiratory functions. AB - Pulmonary function tests and bronchial reactivity to methacholine (MCH) were measured in 34 randomly selected prematures (21 males, 13 females; mean age 11.6 years; mean gestational age 34.9 weeks; mean birth weight 1980 g) and in 34 siblings (22 males, 12 females; mean age 12.5 years, mean gestational age 39.5 weeks; mean birth weight 3030 g). None had suffered neonatal respiratory distress syndrome or had been artificially ventilated. Prematurely born children had a residual volume (RV) and residual volume/total lung capacity (RV/TLC) significantly (P < 0.01) increased compared to controls, although the mean values of both groups were still within the upper limits of normal. Furthermore, an increase of closing volume/vital capacity and closing capacity/total lung capacity (CC/TLC) was observed in most patients with increased RV and RV/TLC. No significant difference was observed for bronchial responsiveness to MCH between prematurely born and control children (11.8% and 5.9% of hyperreactive subjects, respectively). Maternal smoking during pregnancy was prevalent in prematures with impaired respiratory functions. In conclusion clinically normal children of smoking mothers who have survived prematurity but present some respiratory function impairment compared to their born-at-term siblings, should be fully informed and protected from risk factors for chronic obstructive pulmonary disease (COPD) in adult life. PMID- 8444207 TI - Involvement of the central nervous system in renal hypertension. AB - Involvement of the central nervous system (CNS) is a major complication of renal hypertension and is usually due to hypertensive encephalopathy. During a 17-year period we observed 25 children with renal hypertension associated with CNS manifestations in the absence of (group A) and 33 in the presence of advanced renal failure (group B). Convulsions were the most important symptom (65% in both groups combined). Other manifestations were reduced consciousness (69%), visual disturbances (28%), hemiplegia (14%), and cranial nerve palsy (10%). In 56% of children in group A, hypertension was recognised only after appearance of CNS symptoms. Three patients in group A and 19 in group B died. Intracranial haemorrhage associated with hemiplegia was found in 3 cases. From 1970-1977 to 1978-1986 the number of patients and the mortality in group B declined dramatically, probably as a result of improved antihypertensive and renal replacement therapy. In contrast, in group A the number of patients and of CNS symptoms remained similar. The study underlines the importance of frequent blood pressure monitoring in presence of acute or chronic renal disease. PMID- 8444208 TI - Paederus dermatitis: an easy diagnosable but misdiagnosed eruption. AB - Paederus dermatitis is a peculiar irritant contact dermatitis characterised by erythemato-bullous lesions of sudden onset on exposed areas of the body. The disease is provoked by an insect belonging to genus Paederus. This beetle does not bite or sting, but accidental brushing against or crushing the beetle over the skin provokes the release of its coelomic fluid which contains paederin, a potent vesicant agent. Due to the pathogenic mechanism, the morphology and location of the dermatitis change from case to case. The lesion usually resembles the accidental dropping of a caustic or hot liquid. The uncommon association of acute dermatitis with minimal or no complaints, which would be noteworthy in the case of chemical or thermal burns, facilitates diagnosis which is corroborated by the season and by the case history. PMID- 8444209 TI - Family investigations in idiopathic hypercalciuria. AB - We analysed some genetic and environmental factors influencing renal (RH) and absorptive hypercalciuria (AH) the main subtypes of idiopathic hypercalciuria (IH). Their distinction is essential in the prevention and treatment of urolithiasis. Twenty-one children admitted for renal stones had IH (8 RH and 13 AH). Their families were investigated with the participation of a total of 68 family members including 62 first-degree relatives. They were all normocalcaemic. Their urinary calcium excretion was measured on at least two occasions, and they underwent a calcium restriction--calcium loading test. Each subject was interviewed with reference to medical history, drug administration, social conditions, and nutritional habits. Pedigree analysis suggested a higher rate of familiarity and autosomal dominant inheritance of RH whereas no such pattern was found among the relatives of patients with AH. The interviews disclosed a distinct preference for calcium-rich foods in subjects with AH, while RH and normocalciuric individuals preferred a low-calcium diet. We conclude that the subtypes of IH are genetically different. RH is most probably inherited as an autosomal dominant trait (or has at least an autosomal dominant form), whereas AH is more likely to be associated with nutritional factors. PMID- 8444210 TI - Staphylococcus saprophyticus urinary tract infections in children. AB - Staphylococcus saprophyticus commonly causes urinary tract infection (UTI) in young women; in males it is found mainly in the elderly. In this study S. saprophyticus UTI occurred in 59 children (45 girls and 14 boys) below 16 years of age, of whom 20 were less than 13 years of age. The common presentation was dysuria and flank or back pain whereas fever > or = 38.5 degrees C was rare. Radiological investigation performed in 63% of the children revealed no anomalies of importance. Children with S. saprophyticus UTI appear to constitute a group with a low frequency of urinary tract anomalies and with a low risk of UTI caused by other bacteria. PMID- 8444211 TI - The effect of formula versus breast feeding and exogenous vitamin K1 supplementation on circulating levels of vitamin K1 and vitamin K-dependent clotting factors in newborns. AB - The influence of breast or formula feeding together with that of a single supplementation of vitamin K1 at birth, on the vitamin K1 level and vitamin K dependent clotting factors were studied in 65 breast and 15 formula fed infants. All breast fed newborns without supplementation (n = 25) had very low serum vitamin K1 at weeks 1 and 6. Oral vitamin K supplementation (n = 22) or i.m. (n = 18) at birth resulted in high serum levels at week 1, while at week 6 the effect had disappeared. Formula fed infants had vitamin K1 values within the normal adult range at all study points. The low serum levels of vitamin K1 were not associated with haemorrhagic disorders or coagulation abnormalities. The mean values of vitamin K1 in maternal sera at weeks 1 and 6 were 2.3 nmol/l and 1.8 nmol/l and in breast milk 2.7 nmol/l and 2.0 nmol/l respectively. No correlation existed between the values in breast milk and maternal serum. To maintain serum levels of vitamin K1 within the adult physiological range, repeated administration of low doses is needed in breast fed newborns beyond 1 week of age. PMID- 8444212 TI - Ondine-Hirschsprung syndrome (Haddad syndrome). Further delineation in two cases and review of the literature. AB - Two unrelated children with congenital central hypoventilation syndrome (CCHS Ondine syndrome) and long segment Hirschsprung disease are reported. Patient 1, a girl, is still alive at 3 years. Patient 2, a boy, died of viral pneumonia at 5.5 years. Continuous mechanical ventilation was necessary for months and those children could never be weaned from the respirator during sleep. Seventeen cases of this complex neurocristopathy are reviewed. Only six children (including our cases) survived beyond 2 years of age. Hypotonia, delay in developmental milestones or epilepsy were frequently observed. Ventilator dependency does not improve with time. Multifocal congenital neuroblastoma occurred in two children. Aetiology is unknown. PMID- 8444213 TI - Adverse reaction to measles immunization. PMID- 8444214 TI - Toxic methaemoglobinaemia after circumcision. PMID- 8444215 TI - Hydrometrocolpos following prenatal dexamethasone treatment for congenital adrenal hyperplasia (21-hydroxylase deficiency). AB - A female with congenital adrenal hyperplasia (21-hydroxylase deficiency) received prenatal dexamethasone treatment. Suppression of the fetal adrenal was initially inadequate but adequate in later pregnancy. The baby showed masculinisation without clitoral enlargement and a narrow urogenital sinus with resulting hydrometrocolpos. It is possible that dexamethasone treatment which is initially inadequate increases the risk of this latter complication. PMID- 8444216 TI - Asymptomatic autoimmune chronic active hepatitis in a male adolescent. AB - We report a 12-year-old boy presenting with smooth muscle antibody-positive auto immune chronic active hepatitis. Suspicion of the diagnosis arose after a routine blood test which revealed abnormal liver function tests. In spite of the presence of cirrhosis and patchy necrosis on liver biopsy, our patient never showed any clinical feature of impaired liver function. This observation demonstrates that auto-immune hepatitis may exist for a long time before clinical symptoms appear and probably explains why some cases of auto-immune hepatitis finally present as fulminant liver failure. PMID- 8444217 TI - Clinical neurological findings of children with acute lymphoblastic leukaemia at diagnosis and during treatment. AB - Serial neurological evaluation was performed on 40 consecutive children with acute lymphoblastic leukaemia (ALL) at the time of diagnosis and during treatment. Abnormal neurological signs were found in 23% of the patients, including some without neurological symptoms on admission. Six patients (15%) had abnormal funduscopy findings, papilloedema or preretinal haemorrhages, and 3 of them had increased intracranial pressure measured in connection with a diagnostic lumbar puncture but without blasts in their CSF. The reason for the increased intracranial pressure remained unclear. The development of neurological symptoms caused by peripheral neuropathy during induction therapy was related to the total dose and duration of vincristine therapy. The most severe walking difficulties, patients moving about on all fours for as long as 6 weeks-5 months, occurred in a group who were significantly younger than the other children (P < 0.03). Fine and gross motor disturbances occurred in 18% and 30% of the whole patient group, respectively, after 2-3 years of therapy. Impaired short-term memory was observed in 21% of the patients after 2-3 years of therapy, indicating impaired CNS function. The results indicate that chemotherapy also seems to influence CNS abilities, since there was no significant difference between the patients treated with or without cranial irradiation. Neurological evaluation of children with ALL at diagnosis and during treatment is of value with respect to abnormal findings which persist and are not caused by leukaemia, in order to determine the types of difficulties involved and to consider intervention. PMID- 8444218 TI - The immune response in iron-deficient young children: effect of iron supplementation on cell-mediated immunity. AB - The effects of iron deficiency on immunity remain controversial. This study was designed to assess the impact of iron supplementation on the immune status, in 81 children aged 6 months-3 years, at high risk for iron deficiency, using a longitudinal double blind randomised and placebo-controlled study. Lymphocytes of iron-deficient children produced less interleukin-2 in vitro. Iron supplementation for 2 months increased mean corpuscular volume, serum ferritin and serum transferrin, but had no effect on the parameters of T-cell mediated immunity. The lower interleukin-2 levels in iron-deficient suggest that cell mediated immunity may be impaired in iron deficiency. PMID- 8444219 TI - Risk factors for mechanical ventilation in respiratory syncytial virus infection. AB - In a prospective study, risk factors for mechanical ventilation were identified in 102 patients with respiratory syncytial virus (RSV) infection admitted to the Sophia Children's Hospital, Rotterdam. Age, weight on admission and prematurity were associated with the need for mechanical ventilation. Using multivariate analysis, only low weight was an independent risk factor for mechanical ventilation. For infants weighing less than 5 kg the relative risk for mechanical ventilation was 4.4 (95% confidential interval 1.3-13.9). PMID- 8444220 TI - Meal-induced thermogenesis in obese children with or without familial history of obesity. AB - Resting metabolic rate (RMR) and the thermic effect of a meal (TEM) were measured in a group of 26 prepubertal children divided into three groups: (1) children with both parents obese (n = 8, group OB2); (2) children with no obese parents and without familial history of obesity (n = 8, OB0); and (3) normal body weight children (n = 10, C). Average RMR was similar in OB2 and OB0 children (4785 +/- 274 kJ/day vs 5091 +/- 543 kJ/day), but higher (P < 0.05) than in controls (4519 +/- 322 kJ/day). Adjusted for fat-free mass (FFM) mean RMRs were comparable in the three groups of children (4891 +/- 451 kJ/day vs 5031 +/- 451 kJ/day vs 4686 +/- 451 kJ/day in OB2, OB0, and C, respectively). The thermic response to the mixed meal was similar in OB2, OB0 and C groups. The TEM calculated as the percentage of RMR was lower (P < 0.05) in obese than in control children: 10.2% +/- 3.1% vs 10.9% +/- 4.3% vs 14.0% +/- 4.3% in OB2, OB0, and C, respectively. The similar RMR as absolute value as well as adjusted for FFM, and the comparable thermic effect of food in the obese children with or without familial history of obesity, failed to support the view that family history of obesity can greatly influence the RMR and the TEM of the obese child with obese parents. PMID- 8444221 TI - Relation between genotype and phenotype in Swedish phenylketonuria and hyperphenylalaninemia patients. AB - Phenylketonuria (PKU) and hyperphenylalaninemia (HPA) are caused mostly by an inherited (autosomal recessive) deficiency in hepatic phenylalanine hydroxylase (PAH) activity. More than 50 PAH mutations have ben reported. The goal of the present study was to examine the molecular basis for the clinical heterogeneity of Swedish PKU and HPA patients. Mutations were identified through allele specific oligonucleotide hybridization or DNA sequencing on 128 of the 176 mutant alleles (73%). Three mutations (R408W, Y414C and IVS12) together accounted for 56% of all mutant alleles and ten relatively infrequent mutations were found on another 17% of all mutant alleles. Patients from 50 of the 88 families (57%) had identified mutations in both PAH genes and allowed use to compare the clinical effects of different combinations of PAH mutations. The in vitro activity of all of these mutations, including the newly identified G272X and delta L364, have been tested in a eukaryotic expression system. There was a strong relationship between the average in vitro PAH activity of the two mutant enzymes and both the phenylalanine tolerance and the neonatal pretreatment serum phenylalanine concentration. This confirms previous observations in Danish and German PKU patients that disease phenotype is a consequence of the nature of the mutations at the PAH locus and not significantly influenced by other loci. The sample population in the previous study did not, however, include mild HPA patients, and the observed correlation is thus restricted to severe and moderate mutant alleles. Since a comparatively high proportion of the Swedish patients were mildly affected, we have provided additional evidence that this correlation is valid throughout a continuous spectrum of clinical varieties.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444222 TI - Low iron stores in infants and children with treated phenylketonuria: a population at risk for iron-deficiency anaemia and associated cognitive deficits. AB - A retrospective study of 53 patients with phenylketonuria (PKU), whose disease was managed with a low-phenylalanine diet, revealed a high incidence of iron depletion (as reflected by subnormal serum ferritin concentrations). Serum ferritin concentrations under 10 micrograms/l were found in one out of six infants aged 5-12 months. Concentrations under 16 micrograms/l were found in 16 of 22 children aged 1-3 years and in 11 of 25 children aged 4-12 years. Dietary iron, estimated from prescribed intakes of medical foods, exceeded the Canadian recommended nutrient intake, suggesting that low stores of iron may be secondary to reduced bioavailability and absorption of iron. These findings suggest that the current dietary management of PKU is associated with an increased risk for low iron stores. Investigators have reported an association in young children between iron-deficiency anaemia and both cognitive and motor disturbances. Children with PKU, already at risk of neurological damage because of phenylalanine neurotoxicity, may be at increased risk as a result of iron depletion. Serum ferritin as well as haemoglobin concentration should be monitored, along with plasma phenylalanine and tyrosine, to ensure optimum treatment of affected children. PMID- 8444223 TI - Intellectual performance of children with maple syrup urine disease. AB - The intellectual performance of 22 children aged 3-16 years with maple syrup urine disease (MSUD) was assessed and compared to a group of early treated phenylketonuria (PKU) children and normal subjects matched by age, sex, nationality, and socio-economic status. All subjects were tested by one examiner only using the age related versions of the non-verbal Snijders-Oomen intelligence test. The mean IQ (+/- SD) score was 74 +/- 14 (range 50-103) in patients with MSUD, 101 +/- 12 (range 87-125) in early treated PKU patients, and 107 +/- 9 (range 90-122) in normal subjects. Intercorrelations indicated that length of time after birth that plasma leucine concentration remained > 1 mmol/l and quality of long-term metabolic control have important influences on IQ. PMID- 8444224 TI - Stable microbubble test for predicting the risk of respiratory distress syndrome: I. Comparisons with other predictors of fetal lung maturity in amniotic fluid. AB - With the advent of surfactant replacement therapy, there is an increasing need for a rapid test of predicting the development of respiratory distress syndrome (RDS). We evaluated the clinical usefulness of the stable microbubble (SM) test in predicting the development of RDS by comparison with other tests in amniotic fluid samples obtained within 12 h before delivery from 40 pregnancies between 23 35 weeks of gestation. These tests included the lecithin/sphingomyelin (L/S) ratio, disaturated phosphatidylcholine/sphingomyelin (DSPC/S) ratio, concentrations of lecithin, DSPC, and surfactant-associated proteins A and B, C (SP-A, SP-B,C). The cut-off value of each test for predicting RDS was determined at a point of maximum diagnostic accuracy. The overall diagnostic accuracy of the SM test was similar to that of other tests. However, both the SM test and the SP B,C concentration had positive predictive values of 100%. We conclude that the rapid (< 10 min) and reliable information obtained by this test should encourage its use in defining a population of neonates with surfactant deficiency in a multicentre trial of prophylactic surfactant therapy. PMID- 8444225 TI - Stable microbubble test for predicting the risk of respiratory distress syndrome: II. Prospective evaluation of the test on amniotic fluid and gastric aspirate. AB - We determined prospectively if the stable microbubble (SM) test on gastric aspirate obtained at birth was as useful as that on amniotic fluid in predicting respiratory distress syndrome (RDS). One hundred and five paired samples of amniotic fluid obtained at delivery from 105 consecutive women with gestation of 35 weeks or less and gastric aspirates from their neonates obtained within 30 min of birth were studied. The SM test with the predefined cut-off value of less than 5 bubbles/mm2 for amniotic fluid and less than 10 bubbles/mm2 for gastric aspirate signified the risk of RDS with the positive predictive value of 100% and 96% and with the negative predictive value of 91% and 84%, respectively. We conclude that the SM test on both amniotic fluid and gastric aspirate obtained at birth is a rapid (< 10 min), simple and reliable procedure for predicting neonates who will develop RDS. It may be used as a bedside test to define a population of neonates with surfactant deficiency in clinical trials of prophylactic surfactant therapy. PMID- 8444226 TI - Randomised controlled trial of albumin infusion in ill preterm infants. AB - We assessed the effect of albumin infusion on weight loss and ventilation requirement in sick premature infants. Thirty infants, median gestational age 29 weeks, were entered into a randomised controlled trial, at a median of 2 days of age. The infants, all with an albumin level < or = 30 g/l, received either 5 ml/kg of 20% albumin or 5 ml/kg of their maintenance fluids (placebo), both given as part of the total daily fluid requirement. The response to the infusion was assessed by comparing two periods; 12 h immediately prior to the infusion and 12 24 h after the infusion. Albumin infusion was associated with a significant increase in albumin level and a significant reduction in weight, but in the placebo group there was a significant increase in weight. There were, however, no significant changes in the peak inspiratory pressure in response to either infusion. There was only a modest reduction (< 15%) in the inspired oxygen concentration, which occurred in both groups, but reached statistical significance only following the albumin infusion. We conclude that our results suggest that albumin infusion in "hypoalbuminaemic" sick preterm infants is unlikely to alter their respiratory status. PMID- 8444227 TI - Maternal haemolysis, elevated liver enzymes and low platelets syndrome: specific problems in the newborn. AB - To evaluate the effects of maternal haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome on the fetus and neonate we retrospectively investigated the outcome of 87 pregnancies. All women showed thrombocytopenia, elevated liver enzymes and haemolysis. None of them died. Nine infants were stillborn (9.9%). Of the 82 liveborn infants, 66 were delivered by caesarean section. Median gestational age of the liveborn infants was 32.6 weeks, mean birth weight was 1576 g +/- 699 g (mean +/- SD). Of these infants, 44% were small for gestational age. Perinatal asphyxia rate was 21.6%. Nine infants died in the 1st week after birth. Complications during admission included neonatal respiratory disease (43.2%), hyperbilirubinaemia (44.7%), persistent ductus arteriosus (16.2%), thrombocytopenia (34%) and hypoglycaemia (16.2%). Artificial ventilation was necessary in 37 infants. Mean duration of admission was 51 days. HELLP syndrome is associated with poor perinatal outcome; the incidence of caesarean section is high and there is an increased risk for preterm birth and growth retardation. No specific neonatal pathology due to maternal HELLP syndrome was found. PMID- 8444228 TI - Meconium aspiration and otitis media in children. AB - Meconium-stained amniotic fluid was recently reported to be significantly correlated with a higher incidence of otitis media during infancy. In order to verify this connection, a case-control study was performed on 71 pairs of infants, with and without meconium aspiration, matched for gestational age, birth weight and sex. Data were collected by questionnaire or telephone, the response rate being 88.7%. No significant difference in incidence of otitis media between the two groups was observed. This study demonstrated that newborns with meconium aspiration are not at greater risk for otitis media in the 1st year of life. PMID- 8444229 TI - Changing pattern of chronic renal failure and renal replacement therapy in children and adolescents: a 20-year single centre study. AB - We analysed the demographic data, clinical course and survival on different forms of renal replacement therapy (RRT) of 374 children and adolescents with chronic renal failure observed between 1969 and 1988 and compared the findings for the four subsequent 5-year periods. The proportion of children below 5 years of age rose from 21% to 47%. With time the incidence of glomerulonephritis increased and that of pyelonephritis decreased. As RRT became more common, more very young children and more adolescents were admitted to the study. In the last 5 years continuous ambulatory peritoneal dialysis (CAPD) and haemodialysis (HD) were performed to the same extent as the initial form of RRT. The time a subject had to wait for a first transplant decreased from 36 to 21 months. Between 1969 and 1988 overall survival on any form of RRT increased to 77% after 10 years of therapy. In the last observation period 2-year patient survival was 100% both on HD and CAPD. First cadaver graft survival after 4 years improved from 25% in 1969 1973 to 69% in 1984-1988. PMID- 8444230 TI - Hip effusion in nephrotic syndrome mimicking septic arthritis. AB - A case of painful bilateral hip effusions resolving spontaneously in the diuretic phase of steroid responsive nephrotic syndrome in a 6-year-old girl is reported. PMID- 8444231 TI - Does vitamin K cause cancer? PMID- 8444232 TI - Congenital central nervous system abnormalities, idiopathic hypopituitarism and breech delivery: what is the connection? PMID- 8444233 TI - Ethnic differences in Helicobacter pylori infection. PMID- 8444234 TI - The pioneers of pediatric medicine. Karl Stolte (1881-1951). PMID- 8444236 TI - Sudden infant death syndrome: the new clothes of the emperor. PMID- 8444235 TI - Probable role of Streptococcus pyogenes in Kawasaki disease. AB - Over the past 25 years, the clinical course of Kawasaki disease has been defined, the prevalence and nature of the cardiovascular effects widely understood, and pathological changes in the most severe cases well described. However, the aetiology and pathogenesis of this puzzling disease have remained unclear, thus specific therapy is not yet available. Because of some close clinical similarities between this disease and streptococcal scarlet fever, particular attention has been paid to the possible role of Streptococcus pyogenes as an aetiological agent in this illness. Until now, however, group A beta-haemolytic streptococci have never been consistently isolated from any patients; in addition, the titre of anti-streptolysin 0 is not raised, and lack of response to antibiotics is a feature of this disease. Our long series of investigations over more than 10 years, which will be covered in the present review, were performed in an attempt at elucidating causative agent(s) of Kawasaki disease. This has led to our firm belief in the probable role of S. pyogenes in the pathogenesis of this disease, despite the lack of fulfillment of Koch's postulates, on the basis of the following findings. Patients with Kawasaki disease recovering from the acute, febrile phase of the illness exhibited an exaggerated cell-mediated reactivity, as measured by the macrophage migration inhibition test, to group A beta-haemolytic streptococci, their pyrogenic exotoxin and streptolysin 0 as well as to several mammalian muscle cell extracts which are allegedly related antigenically to the cell wall and/or cytoplasmic membrane of S. pyogenes. Protoplast-like "spherical bodies" varying in diameter from 0.5 to 1.5 microns, and devoid of cell walls, were detected in the buffy coats of peripheral blood from patients with this disease, and stained distinctly by immuno-electron microscopy using, as a primary antibody, a rabbit antiserum to S. pyogenes- derived protoplasts, and followed by absorption with protoplasts from Staphylococcus aureus and Escherichia coli. Newborn mice infected with S. pyogenes having no capacity to confer cell-mediated immunity even in adult murine hosts, and reinfected 4-6 weeks later with another strain of the same species of bacteria which is able to elicit cellular immunity, showed a lack of humoral response to streptococcal antigens, leaving intact cell-mediated immunity. Such a biased immunological characteristic is an exact counterpart of that of Kawasaki disease patients.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8444237 TI - Restrictive dermopathy: a lethal congenital skin disorder. AB - Restrictive dermopathy is a recently described lethal congenital disorder of the skin with an autosomal recessive mode of inheritance. The rigidity of the skin impairs fetal movements in utero and causes arthrogryposis, as well as highly characteristic facial features and pulmonary hypoplasia. We report two cases of restrictive dermopathy in prematurely born infants, describe the typical pathological findings and discuss this disorder in the context of the fetal akinesia/hypokinesia deformation sequence. PMID- 8444238 TI - Acquired growth hormone deficiency due to pituitary stalk transection after head trauma in childhood. AB - Two patients are reported with growth hormone deficiency due to head trauma in childhood. Although their injuries were outwardly only slight and there was no loss of consciousness and no subsequent neurological deficits, they exhibited gradual growth retardation from the time of the trauma. Provocative endocrinological tests showed growth hormone deficiency and MRI showed transection of the pituitary stalk. These findings suggest that ordinary head trauma, as well as perinatal insult and congenital abnormalities, could be a cause of growth hormone deficiency. PMID- 8444239 TI - The pioneers of pediatric medicine. Isaac Arthur Abt (1867-1955). PMID- 8444240 TI - Problems with the biochemical diagnosis in mitochondrial (encephalo-)myopathies. AB - Patients suffering from a mitochondrial (encephalo-)myopathy have a remarkable clinical heterogeneity. A reliable and extensive investigation must be performed in order to obtain a correct diagnosis, but many factors may influence the ultimate results of these investigations leading, under certain circumstances, to an incorrect diagnosis. Patients selection is of crucial importance. Metabolic examination of body fluids, particularly with respect to lactate accumulation, is used as a selection criterion for further examinations. Numerous aspects associated with this metabolic examination have been critically evaluated, including the phenomenon of other causes of lactic acidaemia apart from mitochondrial disorders. Correct performance of in vivo function tests may contribute to a reduction of the number of missed diagnoses. Selection of the controls for biochemical investigations must be accurately be performed to obtain reliable reference values. Knowledge of the age-dependency of the biochemical parameters is necessary for a correct interpretation. It goes without saying that the choice of the tissue for biochemical investigations is of utmost importance. Knowledge of the tissue-specific occurrence of some defects in the mitochondrial respiratory chain is necessary. The biochemical examinations can be performed both in biopsy and autopsy material but only under certain conditions. Diagnostic approach requires application of reliable biochemical methods which are described. One of the most intriguing aspects in the diagnosis of mitochondrial disorders is the significance of a defect in relation to the residual enzyme activity found in the patient. Moreover, attention is paid to relevant items such as the occurrence of multiple and secondary defects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444241 TI - Endocrine and molecular biological studies in a German family with Albright hereditary osteodystrophy. AB - We examined a German family with five members affected by Albright hereditary osteodystrophy (AHO). The only patient with pseudohypoparathyroidism type Ia (PHP Ia) presented clinically with latent tetany, mental retardation, round face, short stature, brachymetacarpia and calcifications of subcutaneous tissue, heart and brain, whereas all other four members with pseudopseudohypoparathyroidism (pseudo-PHP) showed only subcutaneous calcifications and brachymetaphalangia. The PHP-Ia patient exhibited hypocalcaemia, hyperphosphataemia, elevated immunoreactive parathyroid hormone (PTH), and a blunted response of cyclic adenosine monophosphate (cAMP) in plasma and urine to synthetic 1-38 hPTH. In addition, latent primary hypothyroidism was found. In contrast, all tested healthy family members as well as the patients with pseudo-PHP exhibited normal calcium metabolism including cAMP response to exogenous PTH. In Northern blot experiments all patients with AHO, regardless whether affected by PHP-Ia or pseudo-PHP, revealed significantly reduced mRNA levels coding for the alpha subunit of the G protein that stimulates adenylyl cyclase (Gs alpha), when compared with healthy family members. In contrast, there was no significant difference between healthy and affected subjects with regard to the levels of the mRNA coding for the alpha subunit of Gi alpha-2, the main inhibitory G protein of adenylyl cyclase. The results indicate that reduced expression of Gs alpha is a useful genetic marker in some families with AHO, regardless whether patients are affected by PHP-Ia or by pseudo-PHP. PMID- 8444242 TI - Urinary bladder dysfunction in diabetic children with and without subclinical cardiovascular autonomic neuropathy. AB - The aim of this study was to assess the relationship between bladder dysfunction and impaired cardiovascular reflexes in diabetic children with no clinical symptoms of autonomic neuropathy. After 15 ml/kg of water intake, the time to first sensation to void, the voiding volume, the voiding time, the average and maximum urinary flows, and the time to maximum urinary flow were estimated by sonography and uroflowmetry in diabetic children with and without cardiovascular autonomic dysfunction (CAD), and in a healthy control group. The three groups of children were matched for age, weight and height. CAD was considered to be present if the results of cardiovascular tests were more than 2SD from the mean of healthy controls. Diabetic children with and without CAD had increased time to first sensation to void, voiding volume, and average urinary flow when compared with healthy children. Voiding volume and average and maximum urinary flows were higher in diabetic children with CAD than in those without CAD. Diabetic children with CAD had also a higher maximum urinary flow than diabetic children without CAD and healthy children. Diabetic children with CAD had a longer diabetes duration and a higher mean fructosamine level during the preceding 3 years than those without CAD. These findings suggest that diabetic children may have diminished sensation of bladder filling independent of impaired cardiovascular reflexes, however, the degree of bladder dysfunction parallels with CAD, both depending on diabetes duration and long-term glycaemic control. PMID- 8444243 TI - Orocaecal transit time in patients with Crohn disease. AB - Orocaecal transit time (OCTT) using the lactulose hydrogen breath test was investigated in 16 patients (age 10-19.4 years) with active Crohn disease (CD). Disease activity was assessed by the paediatric CD activity index (PCDAI). OCTT was prolonged in all patients (mean 149.9 min, SD 32.7) relative to healthy age matched controls (mean 56.9 min, SD 11.1). PCDAI was increased (median 48.8, range 32.5), indicating moderate to severe disease in all patients. A close correlation between OCTT and PCDAI (Spearman r = 0.90) was observed. Following nutritional therapy with a semi-elemental diet over a period of 6 weeks OCTT and PCDAI declined, OCTT becoming normal in 4 and PCDAI in 4/12 patients respectively. OCTT provides a sensitive, non-invasive method for the assessment and followup investigations in patients with CD. PMID- 8444244 TI - Cerebrovascular accidents in sickle cell disease. Risk factors and blood transfusion influence. French Study Group on Sickle Cell Disease. AB - This study presents a series of 34 sickle cell patients with one or more cerebrovascular accidents (CVA). Risk factors were studied in a subgroup of 19 patients whose clinical and biological characteristics were compared to those of a group of 444 sickle cell patients without CVA. The only risk factor discovered was a past history of purulent meningitis, which was significantly more frequent in sickle cell patients than in those without CVA (P < 0.0001). No biological or radiological factor affecting the risk of recurrence was found. The risk of recurrence, neurological defects or death after subsequent CVA justify long-term transfusion treatment in patients presenting with a second CVA. However our study shows that 10 patients who were not transfused after their first CVA had no recurrences, (median follow up = 7.9 years; 2-18 years), providing a basis for discussion on the indications of long-term transfusion therapy for sickle cell patients presenting with their first CVA. PMID- 8444245 TI - Evaluation of complement activation in premature newborn infants with hyaline membrane disease. AB - Fifteen premature newborns with hyaline membrane disease causing acute respiratory distress were evaluated for complement activation. A high intrapulmonary right-to-left shunt and marked arterial-alveolar oxygen difference indicated the severity of the respiratory failure. Twenty preterm healthy infants served as controls. Total haemolytic activity, plasma concentrations of complement components and regulatory proteins (C3, C4, C1-inhibitor, factors H and I) as well as activation products (C3a, C3dg, C1rsC1-inhibitor, C3b(Bb)P) gave no evidence of significant complement activation. Functional activity of the ubiquitous regulatory protein C1-inhibitor was significantly reduced without impact on classical pathway activation. These data suggest that, in contrast to the adult form of respiratory distress syndrome, the low-pressure pulmonary oedema characterising hyaline membrane disease is not mediated by activation of the complement system. PMID- 8444246 TI - Cartilage-hair hypoplasia--clinical manifestations in 108 Finnish patients. AB - Cartilage-hair hypoplasia is an autosomal recessive metaphyseal chondrodysplasia with short-limbed short stature, hypoplastic hair, and defective immunity and erythrogenesis. We have analysed the clinical outcome of 108 Finnish patients. Birth length was below -2.0 SD in 70% of the patients; the adult heights ranged from -11.4 SD to -5.2 SD. The sitting height percentage was increased in all but 4 patients. Six patients had normal hair. Increased ligamentous laxity was present in 95%, limited extension of the elbows in 92%, increased lumbar lordosis in 85%, thoracal deformity in 68%, genu varum in 63% and scoliosis in 21% of the patients. Defective cellular immunity had been observed in 88% and increased susceptibility to infections in 56% of the patients. Six patients had died of primary infections. The incidence of malignancies was 6%. Childhood anaemia had occurred in 79% of the patients. It was usually mild, but severe in 14 patients. Hirschsprung disease had been observed in 8, anal stenosis in 1 and oesophageal atresia in 1 patient. The intrafamilial variation of the syndrome was considerable as studied in 16 sibships. PMID- 8444247 TI - Ghosal haemato-diaphyseal dysplasia: a new disorder. AB - We describe two siblings, products of a first cousin marriage, with diaphyseal dysplasia, severe anaemia, leukopenia, and thrombocytopenia. Radiologically, both had wide medullary cavities with discrete cortical hyperosthosis. Bone marrow was hypocellular. These, and six similar cases in the literature [6], suggest that they represent a form of diaphyseal dysplasia differing from Camurati-Engelmann disease by their radiological appearance, associated haematological abnormalities and autosomal recessive inheritance. PMID- 8444248 TI - Bio-electrical impedance analysis for estimation of fat-free mass and muscle mass in cystic fibrosis patients. AB - The nutritional status of cystic fibrosis (CF) patients has to be regularly evaluated and alimentary support instituted when indicated. Bio-electrical impedance analysis (BIA) is a recent method for determining body composition. The present study evaluates its use in CF patients without any clinical sign of malnutrition. Thirty-nine patients with CF and 39 healthy subjects aged 6-24 years were studied. Body density and mid-arm muscle circumference were determined by anthropometry and skinfold measurements. Fat-free mass was calculated taking into account the body density. Muscle mass was obtained from the urinary creatinine excretion rate. The resistance index was calculated by dividing the square of the subject's height by the body impedance. We show that fat-free mass, mid-arm muscle circumference and muscle mass are each linearly correlated to the resistance index and that the regression equations are similar for both CF patients and healthy subjects. PMID- 8444249 TI - Oxygen deficit and blood lactate in prepubertal boys during exercise above the anaerobic threshold. AB - Recent studies have shown that in boys a steady-state of blood lactate is maintained at exercise levels above the anaerobic threshold. Therefore, the explanation hitherto provided for the steeper increase in blood lactate beyond the anaerobic threshold, i.e. the onset of anaerobic metabolism, needs modification. Investigations were carried out in ten boys, aged 11-12 years, during treadmill running. Maximal oxygen uptake (VO2max) and maximal blood lactate were determined during incremental exercise. Subsequently each boy performed four runs at different high constant speeds of 16 min duration, in order to determine maximal steady-state blood lactate. The underlying data also served to estimate roughly the lactate anaerobic threshold. Oxygen uptaken (VO2) was measured at 0.5 min intervals during the initial 7.5 min of each constant speed run. Maximal steady-state blood lactate was 5.6 mmol/l corresponding to 92% of VO2max. The mean blood lactate at which the anaerobic threshold was reached or just exceeded was 2.7 mmol/l corresponding to 82% of VO2max. Oxygen transport transient kinetics were computed from the mean 0.5 min VO2-values during the constant-speed runs near the maximal steady-state blood lactate and from runs near the anaerobic threshold. Half-times of VO2 response were shorter than values previously reported for adults due to a faster increase in VO2 at the onset of exercise. Half-times increased with increasing work rates as did the oxygen deficit, due to a slower increase in VO2 along with a longer time required to attain a steady-state at higher work rates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444250 TI - Increased cerebral blood flow velocities in newborn infants of smoking mothers. AB - Cerebral blood flow velocities (CBFV) were measured by the pulsed Doppler method in 41 infants of smoking mothers and in 59 apparently healthy control infants. Although gestational age, birth weight, and systolic blood pressure were lower in infants exposed to tobacco smoke prenatally, systolic (65 +/- 11 vs. 47 +/- 12 cm/s, mean +/- SD; P < 0.001), mean (36 +/- 6 vs. 25 +/- 6 cm/s; P < 0.001), and diastolic (17 +/- 4 vs 13 +/- 4 cm/s; P < 0.001) CBFVs in the anterior cerebral artery were significantly higher when compared to control infants. Similar differences were seen in the internal carotid and in the basilar arteries. Multiple regression analysis did not reveal differences other than maternal smoking to explain these observations. We conclude that prenatal tobacco smoke exposure is related to increased CBFVs in newborn infants. Further studies should determine whether this relation is not only statistical but causal and whether increased CBFVs are an indicator of prolonged effects of prenatal tobacco smoke exposure. PMID- 8444251 TI - Nitrogen and fat balances in very low birth weight infants fed human milk fortified with human milk or bovine milk protein. AB - The study was designed to compare two different human milk fortifiers in a group of very low birth weight (VLBW) infants by analysing nitrogen and fat balances, serum concentrations of alpha-amino-nitrogen, urea, and prealbumin as well as growth rates when human milk enriched with one of the two studied fortifiers was fed to the infants. Fortifier A contained different bovine proteins, peptides and amino acids and had an amino acid composition comparable to that of the nutritional available proteins in human milk, with carbohydrates, and minerals. Fortifier B was composed of freeze-dried skimmed human milk and minerals to achieve a similar macronutrient composition in both fortifiers. Eleven infants were fed with human milk enriched with fortifier A and 13 with fortifier B. After a 10-day equilibration period, a 3-day metabolic balance was performed. On the 14th day of the study blood was obtained preprandially for serum analysis and growth rates were estimated. The nitrogen absorption rate (93.8% vs 93.5%) as well as the retention rate (80.8% vs 78.5%) were no different between the groups. The fat absorption rate (92.3% vs 91.5%) as well as the weight gain (32.1 vs 31.1 g/day) were similar and there were no differences in the serum parameters studied. The results indicate that feeding VLBW infants with human milk enriched with a well-balanced bovine fortifier fulfil their nutritional requirements as well as diets composed exclusively of human milk protein. PMID- 8444252 TI - Factors associated with variation in plasma copper levels in preterm infants of very low birth weight. AB - At 2-weekly intervals from age 4-14 weeks, the possible effects on plasma copper concentration of gestation, multiple birth, fractional weight change from birth (W/BW) and, up to 10 weeks, average daily total copper intake from birth were explored in 43 preterm infants of very low birth weight. There was no significant association between the logarithm of the plasma copper concentration (ln Cu) and multiple birth at any time and no significant association between ln Cu and gestation was found from 4-12 weeks. From age 4-10 weeks, there was a significant negative correlation between ln Cu and W/BW and at 4, 6 and 10 weeks there was also a significant negative correlation between ln Cu and copper intake. W/BW and copper intake were correlated throughout. At 14 weeks, ln Cu correlated positively with gestation and negatively with W/BW but, at this age, gestation and W/BW were correlated. The maximum total variation (R2) in ln Cu explained by its regression on gestation, multiple birth, W/BW and/or copper intake combined was only about 31% (at 10 weeks). The potential for copper depletion may be greater in rapidly growing infants. PMID- 8444253 TI - Growth and pubertal development in nephropathic cystinosis. AB - In a retrospective investigation growth and pubertal development were evaluated in 30 patients with nephropathic cystinosis. Growth was investigated during the stage of chronic renal insufficiency as well as after successful kidney transplantation and growth rates were related to kidney function. Pubertal development was evaluated in 17 patients between 12 and 25 years of age. Prepubertal growth rates were stable in a range between -2 and -3 height velocity SDS as long as glomerular filtration rate was above 20ml/min per 1.73m2. A decrease in glomerular filtration rate below this threshold was followed by further decrease in height velocity. After kidney transplantation a significant catch-up growth was seen if immunosuppression was performed with cyclosporine A and low dose prednisolone. This did not occur if conventional therapy with azathioprine and high-dose prednisolone was used. Onset of puberty was delayed in all patients. Gonadotropin and oestradiol levels in female patients showed normal fluctuations according to ovulatory cycles. In male patients after puberty there was an increase in gonadotropin levels above the normal range for adult men while testosterone levels remained in the low normal range. These results indicate that adult men with nephropathic cystinosis may develop hypergonadotropic hypogonadism. PMID- 8444254 TI - Labial fusion and asymptomatic bacteriuria. AB - Thirty-three female children with labial fusion were screened for bacteriuria which was defined as the growth of a single micro-organism with < or = 100,000 colony-forming units/ml (> or = 100 x 10(6) colonies/l) in a properly collected urine specimen. Six girls were found to have bacteriuria. In contrast, none of the 33 girls in a control group had bacteriuria. We recommend that a urine culture be performed in girls with labial fusion and that all girls with bacteriuria should be checked for labial fusion. PMID- 8444255 TI - Xanthine calculi presenting at 1 month of age. AB - Xanthinuria is a rare cause of nephrolithiasis and is usually due to an inherited abnormality in purine metabolism. A 5-year 6-month-old boy was assessed for a history of recurrent episodes of renal colic. The child first presented with symptoms due to xanthine calculi at 1 month of age, the youngest presentation we were able to identify. Xanthine calculi, although rare, should be considered in the differential diagnosis of nephrolithiasis and ureterovesical junction obstruction in children. Xanthine calculi should also be considered when symptoms suggestive of urinary tract infection are present but the urine culture is negative, and when an orange-brown sediment is noted in the urine or similar coloured stains are found in the nappy. PMID- 8444256 TI - A retrospective study of patients with the hereditary syndrome of congenital cataract, mitochondrial myopathy of heart and skeletal muscle and lactic acidosis. AB - The objectives of this study were to describe the course of two forms of an hereditary syndrome characterised by congenital cataract, mitochondrial myopathy of heart and skeletal muscle and lactic acidosis. We also sought to determine clinical, physicochemical and histopathological data which might allow early distinction between the two forms. We compared the ages at which clinical and physicochemical signs appeared in 16 patients. In 5 patients, enzyme histochemical and ultrastructural data of skeletal muscle were available and muscle fibre composition analysed morphometrically. In any particular family only one form of the syndrome occurred. Amongst the patients who did not survive (range 14-34 years) 4 patients died in the neonatal period and 7 died at a median age of 23 years. The median age of the survivors was 19 years (range 15-42 years). Outflow obstruction of the left ventricle was noted in four deceased patients at variable times prior to death. The other deceased patients were not examined, but the cause of death was invariably heart failure. In none of the surviving patients was outflow obstruction noted. Enzyme-histochemical and ultrastructural findings were not specific for the course of the disease. In one biopsy, taken at the age of 3.5 months from a patient who survived, strong lipid accumulation was noted. Morphometric analysis showed proliferation of the mitochondria in muscle fibres, which increased during the course of the disease. PMID- 8444257 TI - Progressive neuronal degeneration of childhood (Alpers syndrome) with hepatic cirrhosis. AB - Four children, from two families, suffered from fatal degeneration of the cerebral grey matter. Their disease was characterised by intractable epilepsy, epilepsia partialis continua, progressive deterioration, and terminal hepatic dysfunction. EEG showed marked and distinctive slow wave abnormality, visual evoked responses were diminished, and cerebral atrophy was seen on CT scan. Pathological findings were of neuronal loss and hepatic cirrhosis. The combination of cerebral degeneration, hepatic disease and familial occurrence suggests an inborn error of metabolism with autosomal recessive inheritance. The features described are those of Alpers syndrome, especially the recently delineated subgroup with progressive neuronal degeneration and liver disease. PMID- 8444258 TI - Reduction of potassium in drinks by pre-treatment with calcium polystyrene sulphonate. AB - Dietary potassium intake in patients with chronic renal failure is generally reduced by oral administration of potassium-binding resins. These drugs may cause disturbances of bowel function and have an unpleasant taste. Pre-treatment of drinks with these resins and their subsequent removal may prevent these inconveniences. In four formulas (whole milk, humanised infant formula, apple juice, and orange juice) we were able to lower the potassium content by 50% with calcium polystyrene sulphonate. No important increase of sodium content was observed, as was reported with the use of sodium polystyrene sulphonate. There was a, potentially beneficial, increase of the calcium concentration. PMID- 8444259 TI - Ear disease is not a common complication in cystic fibrosis. AB - Although upper respiratory tract involvement is a common finding in cystic fibrosis (CF), there is no agreement on whether hearing is affected in these patients. We studied 75 CF subjects and 50 healthy age-matched children with the same audiological protocol. An original scoring system was used to quantify the degree of hearing involvement (normal, mild, moderate and severe) in each subject. Prevalence of ear involvement in children with CF was similar to that in age-matched control subjects (25.4% and 18% respectively, P > 0.05). Ear disease in CF was not related to pulmonary disease, radiological sinusitis, nasal polyposis, or use of parenteral aminoglycosides. These data showed that the risk of ear disease in CF was not increased even if patients with severe audiological involvement were described only in the CF group. PMID- 8444260 TI - Cerebral blood flow velocities in the first minutes of life. PMID- 8444261 TI - Hiccups due to midazolam in children. PMID- 8444262 TI - Sensory neuropathy and vitamin B6 treatment in homocystinuria. PMID- 8444263 TI - On the cognitive penetrability of posture control. AB - Postural sway increases with age. The decreased stability associated with postural sway often has been related to the reduced peripheral sensibility in the visual, vestibular, and proprioceptive systems. We examined whether the micropostural adjustments necessary for maintaining balance also require some cognitive processing. Young and older subjects were submitted to an auditory reaction time task while maintaining an upright posture on a force platform. The auditory stimuli were presented randomly when subjects were in a central or in an eccentric less stable postural position in four conditions of vision/surface. If the postural adjustments require some cognitive processing, a more eccentric position of the center of foot pressure (COP) would require more attention than a stable position of the COP because when an eccentric position is identified, a corrective response subsequently needs to be selected, programmed, and executed. The visual and surface conditions were altered to determine if additional attentional resources need to be allocated to the postural task when there is a reduction of the sensory information available. Results showed that as the sensory information decreased, the postural task became increasingly difficult for the elderly and required more of their attentional capacity (as indexed by increases in reaction time). PMID- 8444264 TI - Adult age differences in free recall and category clustering. AB - This experiment used free recall and category clustering methodologies to determine whether older adults, relative to younger adults, are less adept at organizing the to-be-learned material. To assess the role of categorical versus associative relationships upon organization, items that were clear exemplars of their respective categories and had one of two levels of interim associative strength were used. Analyses of the recall data indicated that younger adults recalled more categories, more instances per category, and more total words than did the older adults. Analyses of organizational measures, including both molar and molecular measures of category clustering (a type of secondary organization), and seriation (a type of primary organization), provided evidence for age differences in multiple and divergent modes of organization. Subjects, particularly the younger adults, initially evidenced a seriation strategy and then used one based on category membership. PMID- 8444265 TI - Memory and organization in elderly subjects. AB - Older adults (ages 67-91) and younger adults (ages 16-30) sorted 100 unrelated words into as many categories as they chose, provided labels for those categories, and were given a surprise recall test with or without the labels as retrieval cues. The older adults recalled fewer words, fewer categories, and fewer items per category than the younger adults. Though generally facilitory, cuing did not reduce the age-related differences in recall performance. Clustering was equivalent for the two age groups. The correlation between number of categories used in sorting and number of words recalled was significant for the young adults only, replicating and extending the results reported by Worden and Meggison (1984). The results were discussed in terms of Hunt and Einstein's (1981) distinction between item-specific and relationship processing, and an alternative interpretation was offered. PMID- 8444266 TI - Age differences in summarizing descriptive and procedural texts. AB - This study compared young and older adults' summaries of expository texts under the hypothesis that older adults would be more experienced, hence more accurate, at summarizing texts. Two types of expository texts were used: procedural and descriptive texts. The texts were read by a panel of judges who wrote summaries of each text and identified the central ideas of each text; the judges' summaries were used to prepare lists of the central ideas of each text and to write standard summaries of each text. The participants read four texts, two orally and two silently, and then wrote summaries, which were limited to 50 words. Words-per minute reading times were collected and the summaries were scored on two measures of content, how many ideas were reproduced from the original texts and the proportion of central ideas that were reproduced, and two measures of length, the number of sentences and the number of words. Although the older adults read more slowly than the young adults, the older adults reproduced more total and central ideas than the young ideas. PMID- 8444267 TI - Influence of aging and practice on piloting tasks. AB - We examined how pilot age influences radio communication and routine flying tasks during simulated flight, and if practice reduces age differences in these tasks. The communication task involved reading back and executing messages with four commands (heading, altitude, communication frequency, transponder code). Routine flying tasks included takeoff, visual approach, and landing. Fifteen older (X = 38.4 years) and 16 younger (X = 26.1 years) private-license pilots flew 12 flights involving these tasks. Age differences were found in the communication task; older pilots read back and executed controller messages less accurately. However, age differences were not significant for any of the routine flying tasks except the approach. Age differences in communication performance were not reduced by practice, with older and young pilots improving at roughly the same rate across flights. These results are consistent with previous research showing age-related declines in working memory capacity. Capacity declines would produce greater age differences on communication than on routine flying tasks because the communication tasks imposed a greater load on working memory. PMID- 8444268 TI - Evidence of direction loss in elderly movement preparation is not due to spatial orienting effects. AB - Twenty elderly and young subjects performed matched movement plan restructuring and spatial orienting tasks. In the restructuring task, a precue stimulus was presented for 200 ms, followed by a preparation (PI; 250, 500, 1000, or 2000 ms), and the target stimulus. On 75% of the trials, the precue specified the aiming movement response enabling movement plan preparation concerning parameters of arm and direction. On 25% of the trials, the precue incorrectly specified the response requiring movement plan restructuring. The orienting task assessed shifts in perceptual localization of the precue and target stimuli for restructuring task conditions. At PIs of 1000 and 2000 ms, elderly, but not young, subjects restructured a movement plan for direction more quickly than for arm or both parameters. Spatial orienting shifts did not account for these effects. PMID- 8444269 TI - Life goals, satisfaction, and self-rated health: preliminary findings. AB - Several recent studies have suggested that a better understanding of health and psychological well-being in later life requires insights into the life goals and motivations of research participants. However, goal importance has not been examined separately from goal achievement. This distinction is important for a more fine-grained analysis of how goals may relate to adaptive outcomes among older adults. Data from surviving respondents of the Duke Second Longitudinal Study were analyzed in order to replicate and extend results from previous studies. Interestingly, a differential pattern of predictors was found for health and satisfaction. The rated importance of goals accounted for a significant portion of the variance in health, but was not predictive of satisfaction, whereas rated achievement of goals was predictive of health and satisfaction. Results are discussed in relation to theories of motivation in later life. PMID- 8444270 TI - The regulation of megakaryocyte polyploidization and its implications for coronary artery occlusion. AB - Polyploidization is a distinctive feature of megakaryocyte differentiation. The physiological meaning and the regulation of this process are obscure. Megakaryocyte ploidy varies in normal biology and in disease. Here we review the evidence suggesting that ploidy changes may have a role in the determination of platelet reactivity and in the aetiology of coronary artery occlusion. We also present a hypothesis that may serve as a framework to explore the regulation of megakaryocyte polyploidization at the molecular level and also may provide a rational basis to explain the occurrence of ploidy changes in ischaemic heart disease. PMID- 8444271 TI - Detection and localization of cytokine immunoreactivity in retro-ocular connective tissue in Graves' ophthalmopathy. AB - Paracrine interactions between fibroblasts residing in the retro-ocular space and infiltrating lymphocytes/macrophages are thought to be of central importance in the pathogenesis of Graves' ophthalmopathy (GO). Although various roles have been suggested for interferon-gamma (IFN gamma), tumour necrosis factor-alpha (TNF alpha) and interleukin-1 alpha (IL-1 alpha) in GO, their actual presence in Graves' retro-ocular connective tissue has not been demonstrated. We examined surgical specimens obtained during orbital decompression from patients with severe GO (n = 6), and from normal individuals (n = 5), for the presence of IFN gamma, TNF alpha and IL-1 alpha. We used immunohistochemical methods on frozen tissue sections and primary fibroblast cultures, and sodium dodecylsulfate polyacrylamide-gel electrophoresis of tissue extracts and tissue culture supernatants. In addition, immunohistochemical staining of tissues for characterization of the mononuclear cell infiltrates was performed. Aggregates of mononuclear cells in retro-ocular connective and fatty tissue were found in five of six GO tissue specimens, but in none of the control specimens. We detected immunoreactivity for the three cytokines (IFN gamma, TNF alpha and IL-1 alpha) in the five GO tissue specimens that contained mononuclear cell aggregates. In addition, IL-1 alpha immunoreactivity was demonstrable in primary and subsequent GO fibroblast cultures and in their supernatants. In contrast, no immunoreactivity for any of these cytokines was detected in tissue specimens, primary cultures or culture supernatants derived from normal individuals. The presence of mononuclear cell infiltrates and associated immunoreactivity for IFN gamma, TNF alpha, IL-1 alpha in retro-ocular connective tissue derived from patients with GO suggests that the previously demonstrated in vitro functions of these cytokines may indeed be operative in vivo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444272 TI - Biotransformation of orally administered ursodeoxycholic acid in man as observed in gallbladder bile, serum and urine. AB - The aim of this study was to evaluate the biotransformation of orally administered ursodeoxycholic acid in man. The distribution of ursodeoxycholic acid and its metabolites in gallbladder bile, in serum and in urine with emphasis on separation of their unconjugated, amidated and sulfated species in particular, was investigated. Seven gallstone patients were given 750 mg of ursodeoxycholic acid daily for 2-3 weeks. Six gallstone patients who did not receive ursodeoxycholic acid served as controls. Ursodeoxycholic acid became the major bile acid in gallbladder bile contributing 43% to total bile acids. 2% of biliary ursodeoxycholic acids were in the unconjugated form, 87% in the amidated form and 11% in the sulfated form. Iso-ursodeoxycholic acid was found in bile in small amounts and was present only as the sulfated species and not as the amidated one. Other metabolites of ursodeoxycholic acid tentatively identified in bile were 1 beta, 12 beta, 6 alpha- and 21,22-hydroxylated derivatives of ursodeoxycholic acid. Lithocholic acid in bile tended to increase under ursodeoxycholic acid treatment and was positively correlated to ursodeoxycholic acid. The concentration of cholic acid in bile decreased significantly whereas the levels of deoxycholic acid and chenodeoxycholic acid did not change. Total bile acid concentration in serum and excretion of bile acids in urine increased from 5.4 +/ 1.1 to 18.4 +/- 9.5 mumol l-1 (mean +/- SD, P < 0.005) and from 5.6 +/- 1.3 to 13.1 +/- 7.9 mumol g-1 creatinine (mean +/- SD, P < 0.05) after ursodeoxycholic acid ingestion mainly due to spillover and excretion of ursodeoxycholic acid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444273 TI - Suppression of lipolysis in normal man does not inhibit recovery from insulin induced hypoglycaemia. AB - Pharmacological suppression of lipolysis is being increasingly used in the treatment of diabetic hyperlipidaemia. Although theoretical hazard of such treatment is that recovery from hypoglycaemia might be impaired. Seven normal subjects were therefore studied on two occasions, following treatment with a single dose of either acipimox 250 mg or placebo. Hypoglycaemic recovery was unaffected, despite effective suppression of plasma non-esterified fatty acid levels with acipimox. The results suggest that under these conditions activation of lipolysis may not be essential to recovery from hypoglycaemia. PMID- 8444274 TI - Effect of jejunal infusion of different caloric loads on pancreatic enzyme secretion and gastro-intestinal hormone response in man. AB - It has recently been demonstrated that the infusion of a high caloric load (3.3 kcal min-1 = 14.0 kJ min-1) into human upper jejunum inhibited pancreatic enzyme and bile salt secretion. The aim of the present study was to investigate whether this phenomenon was mediated by gastrointestinal hormones which interfere with pancreatic secretion. In six healthy volunteers, jejunal infusion of 1.3 kcal min 1 (5.5 kJ min-1) did not modify secretion of lipase and chymotrypsin to any significant extent compared with saline infusion, but the rate of 3.3 kcal min-1 (14.0 kJ min-1) resulted in an inhibition. Somatostatin and pancreatic polypeptide, which are known to inhibit exocrine pancreatic secretion, remained unchanged during jejunal nutrient infusion. The inhibition of pancreatic enzyme secretion was observed in temporal relationship with an increase of the stimulators of pancreatic exocrine secretion such as secretin, neurotensin, and CCK. The existence of an hitherto undefined inhibitor and a feedback mechanism is postulated. PMID- 8444275 TI - Effects of oral calcium supplementation on intestinal bile acids and cytolytic activity of fecal water in patients with adenomatous polyps of the colon. AB - Calcium has been proposed to prevent colon cancer in subjects at risk for this tumour. This effect is supposed to be due at least in part to binding the bile acids to calcium, making them insoluble and harmless. To evaluate the effects of oral calcium supplementation on intestinal bile acids, 19 patients with adenomatous colonic polyps were supplemented with 35.5 mmol Ca2+ daily for 12 weeks. Duodenal bile, 24-h feces and 24-h urine were collected before and at the end of the 12-week period. In duodenal bile proportional concentration of cholic acid increased (38 +/- 4 vs. 51 +/- 3%, P < 0.001), whereas that of chenodeoxycholic acid decreased (35 +/- 3 vs. 25 +/- 2%, P < 0.01). Total fecal bile acid excretion increased (950 +/- 126 vs. 1218 +/- 137 mumol 24 h-1, P < 0.01), with proportional concentrations of the main primary and secondary bile acids remaining the same. Cytolytic activity of fecal water, measured by the degree of lysis of erythrocytes by the water, decreased (45 +/- 8 vs. 30 +/- 7%, P < 0.05). Total excretion of calcium increased as expected from the supplementary dose. It is concluded that calcium supplementation markedly affects intestinal bile acids and lytic activity of fecal water and that, in view of similar results during 1-week calcium supplementation in young healthy subjects, these effects remain constant over at least 3 months and occur both in healthy persons and in patients at increased risk for colon cancer. PMID- 8444276 TI - Mechanism of the lipid-lowering effect of ethyl all-cis-5,8,11,14,17 icosapentaenoate. AB - The effect of highly purified ethyl all-cis-5,8,11,14,17-icosapentaenoate (EPA-E) on cholesterol metabolism in rats was examined to clarify the mechanism of its hypolipidemic action. Pretreatment with EPA-E reduced the increase in plasma radioactivity after oral administration of [14C]cholesterol. The conversion of [14C]3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) to [14C]mevalonic acid was significantly inhibited in liver microsomes obtained from rats treated with EPA E. There was an increase in free cholesterol and a marked rise in the eicosapentaenoic acid (EPA) content of phospholipids in these microsomes. EPA-E restored the suppression of biliary secretion induced by feeding a casein-rich diet to bile duct-cannulated rats. Furthermore, when serum lipoprotein (d < 1.210) from rats given EPA-E was i.v. injected into normal rats, a more rapid elimination of cholesterol was observed as compared to that in rats injected with lipoprotein from EPA-E-untreated rats. This rapid clearance was found in the lipoprotein fractions of d < 1.006 and 1.006 < d < 1.063. These findings suggest that EPA-E has an inhibitory effect on intestinal cholesterol absorption and hepatic cholesterol biosynthesis, and an enhancing effect on hepatic biliary secretion. EPA-E would also seem to cause modification of serum lipoproteins, whereby their clearance from the serum is increased. PMID- 8444277 TI - Age-related decrease of the NMDA receptor-mediated noradrenaline release in rat hippocampus and partial restoration by D-cycloserine. AB - The release of [3H]noradrenaline ([3H]NA) evoked by N-methyl-D-aspartate (NMDA) from superfused rat hippocampus synaptosomes was monitored during aging. The maximal effects of NMDA decreased with age from 50% (1.5 months) to 10% enhancement (24 months). Quisqualic acid (100 microM) also enhanced [3H]NA release. Its effect decreased with age with a pattern partly different from that of NMDA. Glycine (1 microM) potentiated the [3H]NA releasing effect of 100 microM NMDA. Unexpectedly, the potentiation which amounted to 50% at 1.5 months, reached almost 200% and 300% in the 18- and 24-month-old rats, respectively, thus compensating in part for the age-related loss of the NMDA-induced effect. Concentration-response relationships for glycine at 3 vs. 24 months suggest that the glycine receptor is superresponsive in the aged brain. This may be due to more efficient glycine removal or/and to impaired release since uptake of the amino acid was increased by 350% in 24- vs. 3-month-old rats, while the K(+) evoked tritium release from synaptosomes prelabeled with [3H]glycine was decreased. D-Cycloserine, although about 10 times less potent than glycine, strongly enhanced the NMDA-evoked [3H]NA release and may prove useful in cognitive deficits associated with aging and dementia. PMID- 8444278 TI - Involvement of thromboxane A2 in bronchial hyperresponsiveness but not lung inflammation induced by bacterial lipopolysaccharide in guinea pigs. AB - We examined both a possible association of bronchial hyperresponsiveness with lung inflammatory responses and the role of thromboxane (Tx) A2 in these responses after lipopolysaccharide (LPS) exposure in guinea pigs treated with metyrapone, a cortisol synthesis inhibitor. The increase in bronchial responsiveness to i.v. acetylcholine was transient, with a peak at 2 h after LPS exposure, which was associated with increases in TxB2 and tumor necrosis factor in bronchoalveolar lavage (BAL) fluid. However, the levels of 6-keto prostaglandin (PG) F1 alpha, interleukin-1 and interleukin-6 in BAL fluid, and the influx of leukocytes in airway and pulmonary edema were not associated with bronchial hyperresponsiveness. Oral administration of S-1452, a selective TxA2 receptor antagonist, markedly suppressed bronchial hyperresponsiveness without affecting cellular responses, pulmonary edema and production of PGs and cytokines. These findings suggest that LPS-induced bronchial hyperresponsiveness is dependent on secondarily generated TxA2, which appears to be independent of lung inflammation. PMID- 8444279 TI - Adenosine A1 receptors mediate the presynaptic inhibition of calcitonin gene related peptide release by adenosine in the rat spinal cord. AB - Electrical field stimulation evoked a reproducible outflow of calcitonin gene related peptide-like immunoreactivity (CGRP-LI) from the dorsal half of the rat spinal cord, an effect which was abolished by prior application of capsaicin, tetrodotoxin or removal of extracellular Ca2+. Adenosine (EC50 3.2 microM) and the selective adenosine A1 receptor agonist N6-cyclohexyladenosine (EC50 8.2 nM) inhibited evoked CGRP-LI outflow, while the selective adenosine A2 receptor agonist CGS-21680 was ineffective up to 10 microM. The action of adenosine was prevented by the adenosine A1 receptor selective antagonist 8-cyclopentyl-1,3 dipropylxanthine (30 microM), which did not affect CGRP-LI release on its own. PMID- 8444280 TI - Neurotensin participates in self-stimulation of the medial prefrontal cortex in the rat. AB - The effects of intracerebral microinjections of neurotensin and xenopsin on self stimulation of the medial prefrontal cortex of the rat were studied. Unilateral microinjections into the medial prefrontal cortex of neurotensin at doses of 0.625, 1.25, 2.5, 5 and 10 nmol produced a dose-related decrease of self stimulation in the ipsilateral medial prefrontal cortex. Self-stimulation of the contralateral medial prefrontal contex, used as control, was not affected by the microinjections. Similar results were found with the neurotension-like octapeptide, xenopsin. Unilateral microinjections of xenoposin into the medial prefrontal cortex, at doses of 1.8, 3.6, 7.2 and 14.4 nmol produced a dose related decrease of self-stimulation of the ipsilateral medial prefrontal cortex. Self-stimulation of the contralateral medial prefrontal cortex was not affected. These results suggest that neurotensin is part of the neurochemical substrate of self-stimulation in this cortical area. PMID- 8444281 TI - Acamprosate (calciumacetylhomotaurinate) decreases postsynaptic potentials in the rat neocortex: possible involvement of excitatory amino acid receptors. AB - Acamprosate (calciumacetylhomotaurinate) is used therapeutically against relapse in weaned alcoholics. In the present study, the mechanism of action was investigated by making intracellular in vitro and extracellular in vivo recordings from rat neocortical neurons. Acamprosate (0.1-1 mM) added to the perfusion fluid in vitro reduced excitatory and inhibitory postsynaptic potentials and the depolarizing responses evoked by iontophoretic application of the excitatory amino acids, L-glutamate, L-aspartate, L-homocysteate and N-methyl D-aspartate, but did not alter the responses to gamma-aminobutyric acid. Acamprosate decreased electrical excitability without apparently changing membrane potential, input resistance, afterhyperpolarization, or threshold and amplitude of the action potential. In vivo iontophoretic application of acamprosate reduced the extracellularly recorded unit activity elicited by iontophoretically applied L-glutamate, whereas spontaneous discharges remained unaffected. These data suggest that acamprosate reduces the postsynaptic efficacy of excitatory amino acid neurotransmitters and lowers neuronal excitability in the neocortex of the rat. PMID- 8444282 TI - (R)- and (S)-8-acetyl-2-(dipropylamino)tetralin (LY-41): two novel 5-HT1A receptor agonists. AB - Interactions between central 5-HT1A receptors and the enantiomers of LY-41, a 2 aminotetralin derivative related to 8-OH-DPAT (8-hydroxy-2 (dipropylamino)tetralin), were studied. Both enantiomers of LY-41 behaved as potent 5-HT1A receptor agonists in rats, inducing the 5-HT behavioural syndrome, decreasing body temperature and inhibiting the cage-leaving response. The behavioural syndrome and the hypothermia were antagonized by the 5-HT1A receptor antagonist, (S)-UH-301. The LY-41 enantiomers also reduced brain 5-HTP accumulation in rats treated with a decarboxylase inhibitor. The pharmacology of the enantiomers of LY-41 appeared similar to that of 8-OH-DPAT. However, it is noteworthy that the stereoselective interaction of 5-HT1A receptors with LY-41 was opposite to that of 8-OH-DPAT. Thus, (R)-8-OH-DPAT was more potent than (S)-8 OH-DPAT, whereas (S)-LY-41 appeared to be more potent than (R)-LY-41. PMID- 8444283 TI - Ceruletide, a cholecystokinin-like decapeptide, differentially reduces the stimulant effect of MK-801 and ketamine: evaluation by discrete shuttle avoidance in mice. AB - The non-competitive NMDA antagonist, MK-801 (dizocilpine: 0.03-0.3 mg/kg i.p.), a dissociative anesthetic, ketamine (1-20 mg/kg s.c.) and a CNS stimulant, methamphetamine (0.1-1 mg/kg s.c.), dose dependently increased the response rate in mice trained to discrete shuttle avoidance. MK-801 (0.1 mg/kg), ketamine (10 mg/kg) and methamphetamine (0.3 mg/kg) were almost equipotent. The cholecystokinin-like decapeptide, ceruletide, 0.1 micrograms/kg s.c., completely attenuated the response-increasing effect of MK-801 (0.1 mg/kg), although at this dose ceruletide alone did not produce any significant change in the avoidance response. Up to 10 micrograms/kg of ceruletide, which itself decreased the response rate, was required to reduce significantly the response-increasing effect of ketamine (10 mg/kg) and methamphetamine (0.3 mg/kg). On the other hand, haloperidol (0.01-0.1 mg/kg s.c.) decreased both the response rate and the % avoidance dose dependently, and inhibited the response-increasing effects of MK 801, ketamine and methamphetamine to almost the same degree. The present results suggest that comparatively lower doses of ceruletide inhibit selectively the stimulant effect of MK-801. Inhibition of dopamine release from the stored site in the nucleus accumbens may be mainly involved in this interaction. PMID- 8444284 TI - AJ-2615, a long-acting Ca2+ channel antagonist with a novel structure. AB - AJ-2615, a dihydrodibenzothiepin derivative, at 10(-4) M inhibited the peak ICa amplitude of an identifiable Achatina neurone, PON (periodically oscillating neurone), by nearly a half of the control response 30 min after the start of perfusion (ED50: 0.96 x 10(-4) M). The ICa inhibition was still sustained 30 min after washout, indicating that AJ-2615 has long-lasting activity. The compound inhibited the ICa over a wide range of membrane potentials depolarized by the voltage pulse (Vd), but did not change the membrane potential required to produce the maximal ICa (Vd = 0 mV). The additional decrease in ICa amplitude caused by changing from low-frequency (1/5 min) depolarizing pulses to high-frequency (3/min) depolarizing pulses in the presence of AJ-2615 at 10(-4) M was 39.2 +/- 4.5% (mean+S.E.M.; n = 5), indicating use dependence. The steady state inactivation curves were measured in the presence or absence of AJ-2615 at 10(-4) M with a depolarizing prepulse (Vd = varied, duration = 30 s) followed by a depolarizing test pulse (Vd = +10 mV, duration 80 ms), with 2 ms intervals (n = 3): the ratio of AJ-2615 dissociation constant in the resting Ca2+ channel (Kr) and in the inactivated Ca2+ channel (Ki), Kr/Ki, was calculated to be 9.6:1, indicating voltage dependence. PMID- 8444285 TI - Standardised lung function testing. PMID- 8444286 TI - To understand how babies breathe... PMID- 8444287 TI - Rational approach to the diagnosis of Pneumocystis carinii pneumonia (PCP) PMID- 8444288 TI - Inhalation of nitric oxide modulates methacholine-induced bronchoconstriction in the rabbit. AB - Nitric oxide (NO) accounts for the major effects of endothelium-derived relaxing factor. We investigated whether NO, added to the inspired gas, could exert a bronchodilatory action similar to the pulmonary vasodilation described when administering NO during lung vascular constriction. New Zealand White rabbits were intubated and mechanically-ventilated with 30% oxygen during neuroleptanaesthesia. Methacholine (MCh) was nebulized at increasing concentrations from 0.5 to 4.0 mg.ml-1, with or without inhalation of 80 parts per million (ppm) NO. The technique of rapid airway occlusion during constant flow inflation was used for measuring respiratory mechanics, i.e. resistance and compliance of the respiratory system. Methacholine nebulization without NO inhalation raised the resistance from 51 +/- 6 (mean +/- 95% confidence interval) to 107 +/- 52 cmH2O.l-1.s at Mch 4 mg.ml-1. During NO inhalation, nebulization of MCh showed no significant increase in resistance. Arterial oxygen tension (PaO2) and compliance fell to the same extent during methacholine challenge, whether NO was inhaled or not. Closure of small airways may be a mechanism that causes the decrease in PaO2 and compliance observed. This suggests that 80 ppm NO added to the inspired gas modulates the response in central airway tone to nebulized MCh in this rabbit model. However, it appears to have less effect on peripheral airways. PMID- 8444289 TI - Bronchial responsiveness to inhaled propranolol in asthmatic children and adults. AB - Inhaled propranolol (P) was administered to a population which included asthmatic children (30 subjects) and adults (43 subjects): 1) to investigate the determinants of induced bronchial response; 2) to examine the relationship with treatment requirements; 3) to determine the relationship with responsiveness to methacholine (M) and ultrasonically nebulized distilled water (UNDW) (50 subjects); and 4) to establish the short-term repeatability of bronchial response to propranolol compared with methacholine (22 subjects). Bronchial response to propranolol and methacholine was expressed as the cumulative provocative dose (PD20 in mumol) and responsiveness to UNDW as the provocative output (PO20 in ml.min-1) producing a 20% fall in forced expiratory volume in one second (FEV1). Response to propranolol was significantly related to the degree of responsiveness to methacholine, but not to age, gender, presence of atopy, age at asthma onset, or baseline FEV1. PD20P was measurable in all but three subjects. A significant difference in mean PD20M but not in PD20P was found between subjects requiring more anti-asthmatic treatments compared to those without therapy. The difference between geometric mean PD20P and geometric mean PD20M was 14.1. PO20UNDW was measurable in only 21 out of 50 subjects. Both PD20P and PD20M were significantly lower in responders to UNDW than in nonresponders. Reproducibility of PD20P was comparable to that of PD20M (coefficients of repeatability: 1.17 and 1.09). We conclude that bronchial responsiveness to propranolol is safely measurable in most children and adults with asthma. Repeatability of bronchial response to propranolol is comparable to that of methacholine. Moreover, responsiveness to propranolol is not a predictor of treatment requirement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444290 TI - Vascular volume expansion and thermally induced asthma. AB - To determine whether a relationship exists between intravenous infusion of isotonic fluid and reactivity to hyperpnoea, eight normal and eight asthmatic subjects underwent rapid intravascular administration of approximately 2 l of warm normal saline, by itself and before and after hyperventilation of cold air. In the asthmatic subjects, saline infusion mirrored the obstruction seen with hyperventilation; whereas, in normal subjects saline produced more bronchial narrowing than hyperventilation. When the two stimuli were given together, the timing of the infusion altered the asthmatic subjects' responses. Giving fluid early in the hyperventilation challenge blunted obstruction, whereas giving it later amplified the airway narrowing. Similar findings, but on a smaller scale, occurred in normal subjects. These data demonstrate that sudden elevations in intrathoracic vascular volume with warm saline produce airway obstruction that is quantitatively similar to that seen with hyperventilation in asthmatic individuals. They also demonstrate that these two stimuli interact together in such a manner that a common mechanism may exist to account for the decrease in airflow. PMID- 8444292 TI - Force-frequency relationships of in vivo human and in vitro rat diaphragm using paired stimuli. AB - Supramaximal stimuli, with time intervals of 100 ms (10 Hz) to 10 ms (100 Hz), were delivered in pairs to the phrenic nerves, bilaterally, in five seated normal subjects, while transdiaphragmatic pressure swings (Pdi,s) were recorded at relaxed end-expiratory lung volume with airways closed. In fresh diaphragms, Pdi,s increased between 10-20 Hz and reached a plateau between 20-30 Hz. Diaphragmatic fatigue decreased Pdi,s at all frequencies. Pdi,s was assumed to be the sum of two successive responses (T1+T2), T1 being constant at any frequency and equal to a single twitch, T2 being obtained by subtraction. We found that T2 amplitude, which was significantly reduced after fatigue, was fully returned to normal after 15 min rest at high, not at low, stimulation frequencies. The ratio of T2 at 10 Hz over 100 Hz (T2(10/100)) thus decreased from 1.33 +/- 0.05 before fatigue to 0.97 +/- 0.12 after fatigue, and to 0.81 +/- 0.06 after 15 min rest. Similar results were obtained in isolated rat diaphragmatic strips stimulated and fatigued in vitro, from which we found a highly linear relationship (r = 0.94, p < 0.001) between the ratio of T2(10/100) and that of tetanic force at 10 Hz over 100 Hz (P10/100). We conclude that phrenic nerve paired twitches provide similar information when obtained from phrenic tetanic stimulation in terms of diaphragmatic contractility, and the decrease in T2(10/100) ratio indicates diaphragm low frequency fatigue. PMID- 8444293 TI - Effect of pleural effusion on respiratory mechanics, and the influence of deep inflation, in dogs. AB - We wished to study how pleural effusion affects dynamic mechanics of the lung and the chest wall. We also determined if these changes could be reversed by deep lung inflations. Pleural effusion was produced by saline infusion into the pleural space. During the infusion and over the following 2 hours, dynamic elastance and resistance of the lungs, the chest wall and the whole respiratory system were recorded. Dynamic elastance and resistance of the lung increased significantly during fluid loading and were partially, and only transiently, reversed by deep inflations. Dynamic elastance and resistance of the chest wall were little affected by these procedures. Thus, pleural effusion can have significant effects on dynamic elastance and resistance of the respiratory system (ERS, RRS). The transient nature of the change in lung parameters after deep inflation suggests that therapies based on periodic lung inflations may be of little benefit to patients with this condition. PMID- 8444291 TI - Differences in utilization of asthma drugs between two neighbouring Swedish provinces: relation to symptom reporting. AB - Utilization of anti-asthma drugs is rapidly increasing and varies markedly between counties in Sweden. In 1989, the sales in the county of Gavleborg were less than 60% of those in neighbouring Jamtland. In order to study the possible reasons for--and effects of--this difference, an epidemiological survey was started in 1989, the first part of which is reported here. A questionnaire was sent to all 16 yr olds, and to a random sample of 30-39 and 60-69 yr olds, in the two counties. A total of 12,500 questionnaires were distributed. Overall response rate was 90%. A total of 7.2% in Jamtland and 5.8% in Gavleborg (p < 0.01) reported that they had had asthma at some time. A similar significant difference between the counties was also present in response to questions on attacks of shortness of breath, wheezing and self-reported diagnosis of asthma, as well as on use of anti-asthma drugs. There were no statistically significant differences between the counties in positive answers to questions concerning history and symptoms of chronic bronchitis; approximately 5% in the oldest age group. The findings support earlier results indicating a high asthma prevalence in northern Sweden. Contrary to reports from other countries, the prevalence was higher in the colder and less urbanised of the two provinces. We conclude that the differences in drug sales between the counties reflect a difference in prevalence of asthmatic symptoms. PMID- 8444294 TI - Membrane diffusion of the lungs in patients with chronic renal failure. AB - Patients with chronic renal failure (CRF) and haemodialysis treatment usually have a reduced CO transfer factor. The aim of this study was to evaluate the effects of alveolar wall fibrosis and of anaemia on gas diffusion in the lungs. The NO and CO transfer factors of the lung (TLNO and TLCO) were measured, simultaneously, in 15 patients haemodialysed three times a week for 1-10 yrs. Assuming that NO is highly reactive with blood, Tlno is thus directly proportional to the membrane diffusion factor (DmCO). The lung capillary blood volume (Vc) was derived from the set of the two transfer equations. Transfer factors were measured between haemodialysis sessions. All patients but one were anaemic, with haemoglobin concentrations ranging 61-151 g.l-1. All had decreased Vc, and a decreased DmCO was observed in 14 patients. However, after correction for the anaemia, Vc values were normal with the exception of three patients. The percentage decrease in DmCO with respect to normal was correlated with the time elapsed since the first haemodialysis. These results support the idea of a progressive development of haemodialysis-induced chronic lung disease, that may be related to a mechanism of complement activation by a bio-incompatible membrane (Cuprophane). Accordingly, patients with compromised cardiopulmonary functions should be dialysed with a bio-compatible membrane. PMID- 8444295 TI - Measurement of carbon monoxide transfer and lung volume in ventilated subjects. AB - A simple method for measuring lung volume and carbon monoxide transfer factor (TLCO) by a rebreathing technique was assessed in nine healthy volunteers undergoing intermittent positive pressure ventilation (IPPV). Measurements of TLCO, alveolar volume (VA) and carbon monoxide transfer coefficient (KCO) made at three inspired oxygen concentrations (21, 35 and 70%) during IPPV were compared to those obtained during spontaneous breathing. The effects of 10 cmH2O positive end expiratory pressure (PEEP) were also studied. Pulmonary capillary blood volume (Vc) and the diffusing capacity of the alveolar capillary membrane (Dm) were derived. There was a close correlation between measurements of TLCO during IPPV (TLCOIPPV) and spontaneous breathing (TLCOSV) (r = 0.92). Ventilated TLCO was 64 +/- 8% of spontaneously breathing TLCO. There was a close agreement between ventilated and spontaneously breathing measurements of KCO (r = 0.95; mean difference 0.14, 95% limits of agreement +0.37 to -0.09 mmol.min-1 x kPa-1 x l-1). Vc was 92 +/- 23 ml during spontaneous breathing and 72 +/- 21 ml during IPPV (p < 0.05). PEEP of 10 cmH2O significantly increased functional residual capacity (2.3 +/- 0.5 to 3.5 +/- 0.6 l) and decreased TLCO (5.9 +/- 1.0 to 5.3 +/ 1.2 mmol.min-1 x kPa-1), KCO (1.7 +/- 0.2 to 1.1 +/- 0.3 mmol.min-1 x kPa-1 x l 1) and Vc (82 +/- 22 to 56 +/- 20 ml). Dm did not change with PEEP. This simple method may be a useful means of assessing gas exchange and lung volume in ventilated subjects. It showed that PEEP increased lung volume but reduced TLCO and that this reduction appeared to be due to a reduction in capillary blood volume. PMID- 8444296 TI - The large lungs of elite swimmers: an increased alveolar number? AB - In order to obtain further insight into the mechanisms relating to the large lung volumes of swimmers, tests of mechanical lung function, including lung distensibility (K) and elastic recoil, pulmonary diffusion capacity, and respiratory mouth pressures, together with anthropometric data (height, weight, body surface area, chest width, depth and surface area), were compared in eight elite male swimmers, eight elite male long distance athletes and eight control subjects. The differences in training profiles of each group were also examined. There was no significant difference in height between the subjects, but the swimmers were younger than both the runners and controls, and both the swimmers and controls were heavier than the runners. Of all the training variables, only the mean total distance in kilometers covered per week was significantly greater in the runners. Whether based on: (a) adolescent predicted values; or (b) adult male predicted values, swimmers had significantly increased total lung capacity ((a) 145 +/- 22%, (mean +/- SD) (b) 128 +/- 15%); vital capacity ((a) 146 +/- 24%, (b) 124 +/- 15%); and inspiratory capacity ((a) 155 +/- 33%, (b) 138 +/- 29%), but this was not found in the other two groups. Swimmers also had the largest chest surface area and chest width. Forced expiratory volume in one second (FEV1) was largest in the swimmers ((b) 122 +/- 17%) and FEV1 as a percentage of forced vital capacity (FEV1/FVC)% was similar for the three groups. Pulmonary diffusing capacity (DLCO) was also highest in the swimmers (117 +/- 18%). All of the other indices of lung function, including pulmonary distensibility (K), elastic recoil and diffusion coefficient (KCO), were similar. These findings suggest that swimmers may have achieved greater lung volumes than either runners or control subjects, not because of greater inspiratory muscle strength, or differences in height, fat free mass, alveolar distensibility, age at start of training or sternal length or chest depth, but by developing physically wider chests, containing an increased number of alveoli, rather than alveoli of increased size. However, in this cross-sectional study, hereditary factors cannot be ruled out, although we believe them to be less likely. PMID- 8444297 TI - Cost effectiveness of the induced sputum technique for the diagnosis of Pneumocystis carinii pneumonia (PCP) in HIV-infected patients. AB - The purpose of this study was to assess: 1) the percentage of human immunodeficiency virus (HIV)-infected patients with suspected Pneumocystis carinii pneumonia (PCP) but unable to undergo the induced sputum procedure, together with the reasons involved; 2) the sensitivity and specificity of induced sputum procedure, using conventional stains and an immunofluorescence test; and 3) the cost of introducing induced sputum procedure for the diagnosis of PCP. One hundred and thirty eight HIV-infected patients with suspected PCP underwent induced sputum procedure and bronchoalveolar lavage (BAL). P. carinii was identified in induced sputum and BAL samples using conventional and immunofluorescence staining. The economic analysis took into account the direct costs of the two procedures. The induced sputum procedure was either not feasible or unsuccessful in 29% of the patients. The sensitivity of induced sputum, using conventional and immunofluorescence staining, was 0.27 and 0.56 respectively. The economic analysis showed that the two strategies (systematic BAL versus BAL only after negative induced sputum) are equivalent in cost terms when the induced sputum to BAL cost ratio is equal to the product of the prevalence of PCP by the sensitivity of induced sputum procedure. We conclude that the immunofluorescence test should be the reference technique for induced sputum samples, whilst conventional stains are more clinically relevant for BAL samples. The cost of introducing induced sputum should take into account the sensitivity of induced sputum and the prevalence of PCP in the suspected population. PMID- 8444298 TI - Treatment of hydatid disease in childhood with mebendazole. AB - The general characteristics of 56 childhood cases of cystic hydatid disease were analysed and the results of mebendazole therapy versus surgery were verified. Pulmonary radiograms and ultrasonography were used in the diagnosis. The cysts were localized primarily to the lungs. Twenty seven patients were surgically treated, with eight having recurrence after a mean period of 3.6 yrs. Thirty patients received regular mebendazole treatment, in a dose of 50 mg.kg-1 with a mean duration of treatment of 11.7 months. Twenty one patients were cured and discontinued the therapy. Nine still use the drug, seven of whom have had dramatic improvement, while the other two have minimal radiographic changes but subjective improvement in general condition. The lung cysts vanished leaving minimal scars, whilst the liver cysts turned into inactive forms. The surgically treated and drug-treated groups were similar in age, duration and severity of the disease. The recurrence rate of drug-treated children (1 out of 20) was lower than that of the surgically-treated children (8 out of 27); however, this was not statistically significant. PMID- 8444299 TI - Alveolar haemorrhage as a presenting feature of myeloma. AB - An immunoglobulin A (IgA)-paraprotein secreting myeloma was found to be the underlying disease in a patient who presented with alveolar haemorrhage. The diffuse pulmonary bleeding stopped after initiation of treatment consisting of corticosteroids and melphalan. A paraprotein mediated lesion of the alveolar capillary membrane was suspected but could not be demonstrated. PMID- 8444300 TI - Governor Chiles assigns 'Red Ribbon Panel on AIDS': Barbara Russell selected. PMID- 8444301 TI - Is the nurse specialist a marketable commodity? PMID- 8444302 TI - Susan Farese provides consulting; poetry. PMID- 8444303 TI - ANA meets with transition team to discuss AIDS. PMID- 8444304 TI - Department of Labor looks at foreign-trained nurses. PMID- 8444305 TI - "Operation Andrew": the role of the National Guard during hurricane Andrew. PMID- 8444306 TI - The role of navy nurses during the aftermath of Andrew. PMID- 8444307 TI - Good news, for a change. PMID- 8444308 TI - Guidelines for preventing transmission of HIV and hepatitis B from health care workers to patients. Division of Public Health, Delaware Health and Social Services. PMID- 8444309 TI - A more complete view of physical therapy. PMID- 8444310 TI - Address of the president of the AMA. PMID- 8444311 TI - Interaction of phospholipids with proteins and peptides. New advances III. AB - 1. The review deals with the recent achievements in the study of the various interactions of phospholipids with proteins and peptides. 2. The interactions are classified according to the hydrophobic, hydrophilic or mixed character of the interactive forces. 3. The effect of the interaction on the structure and biological activity of the interacting molecules is also discussed. PMID- 8444312 TI - Neutrophil mediated myocardial injury. AB - 1. Activated polymorphonuclear neutrophils (PMN) were shown to exacerbate ischemic myocardial injury and their activation is modulated by complement system, platelet activating factor, arachidonic acid metabolites, adenosine and nitric oxide. 2. Mechanisms of injurious PMN effect on ischemic myocardium are related to both mechanical and biochemical processes. 3. Activated PMN aggregate and adhere to endothelium that results in capillary plugging and subsequent impairment of coronary blood flow as well as participating in the development of endothelial cell edema. 4. PMN-related biochemical damage of ischemic myocardium is a result of the release of cytotoxic free oxygen radicals and proteolytic enzymes as well as vasoconstrictor leukotriene B4 and leukotoxin. PMID- 8444313 TI - The effect of orotic acid treatment on the energy and carbohydrate metabolism of the hypertrophying rat heart. AB - 1. Adenine nucleotide concentrations in normal and one day hypertrophied hearts of untreated, orotic acid (OA), uridine, uracil, dihydroorotate and reserpine pretreated rats were measured. OA treatment increased the ADP concentration 5 fold in one day hypertrophied hearts. Neither uracil, uridine, dihydroorotate nor reserpine treatments changed ADP or total adenylate concentrations at one day of hypertrophy. 2. The adenine nucleotide ratio (ANR) at 0.263 x 10(3) M-1 and the energy charge (0.66) were at their lowest values in OA and in reserpine treated one day hypertrophying hearts. The temporal decline in the indices of energy metabolism corresponded with the OA induced maximum stimulation of contractility and maximum rates of protein, RNA and glycogen synthesis. 3. The phosphorylation state of the adenine nucleotides (PSAN) was both the most sensitive and the best predictive index of the cellular energy status in normal and hypertrophying hearts. The pronounced ability of OA treatment to energize myocyte cytoplasm was shown by the 9- and 6-fold greater values of PSAN over ANR in one and three day hypertrophied hearts. The enhanced PSAN may be the key factor in the mechanism of OA induced enhancement of contractile and synthetic functions of the heart in compensatory hypertrophy. 4. The development of myocardial hypertrophy in untreated rats resulted in a 36% reduction in the cytoplasmic NAD/NADH ratio. In rats treated with OA this redox couple of the hypertrophying heart was more oxidized and was increased by 30% to restore it to the value range of normal heart. 5. The regulatory status of the glycolytic pathway in untreated and OA treated hypertrophying hearts was assessed by comparisons of the mass action ratio (MAR) and equilibrium constants for each of the individual glycolytic reactions. There was an OA induced 2.7-fold increase in glycogen, UDP-glucose and total uridine nucleotides in hypertrophied hearts. The concentrations of seven out of ten glycolytic intermediates, including pyruvate and lactate were increased as a consequence of OA treated hypertrophy. Glycolytic flux was not stalled, rather the pathway was "more open" permitting greater throughput of intermediates with individually increased levels of selected metabolites. OA stimulated hypertrophy did not change the canonical control of glycolysis by the activities and individual MAR values of phosphofructokinase and pyruvic kinase. 6. Elevated levels of Glu 6-P, Fru 6-P and DHAP can force glycolytic intermediate entry into the non-oxidative reaction segment of the pentose pathway (PP), thereby elevating Rib 5-P concentration by reversal of the conventional flux direction of PP.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8444314 TI - A tumor-associated 120 kDa nuclear protein: characterization using a monoclonal antibody and a partial cDNA clone. AB - 1. We have established a murine hybridoma (F86) that secretes a monoclonal antibody (MoAb) specific for a 120 kDa nuclear protein (p120). p120 is expressed in all human cell lines investigated, whether of tumor or normal cell origin. 2. However, expression of p120 is significantly higher in neoplastic cells than in normal cells. The amount of p120 is relatively constant through the cell cycle and does not appear to be modulated by 72 hr serum starvation. 3. These results suggest that p120 plays some role in nuclear events associated with neoplastic phenotypes rather than in cell proliferation. 4. In situ immunofluorescence analyses indicate that p120 is located exclusively in nuclei of interphase cells. It is not present in nucleoli. 5. During mitosis, p120 is distributed in the cytoplasm and is not associated with condensed chromosomes which, together with RNAse experiments, suggests that it may be associated with hnRNA or hnRNP particles. 6. Western blot analyses indicate that p120 consists of two molecular weight forms which differ by 2-3 kDa in reduced SDS-PAGE, and several isoelectric variants in the acidic range. 7. Fractionation studies indicate that p120 has accessible free sulfhydryl group(s) and can bind ssDNA and heparin. 8. A partial cDNA clone, encoding the carboxyl terminus of p120, was isolated from a lambda gt11 library which had been prepared from human hepatoma cells (KYN-1). 9. Sequence analysis of the open reading frame revealed two possible nuclear localization sequences and several clusters of acidic amino acid residues, including a continuous run of 11 glutamic acid residues. 10. Northern blot analyses of human hepatoma RNA revealed hybridization to three transcripts which are about 4.1, 3.6, and 0.6 kb in size. 11. Dot blot analyses show that these transcripts are about 10-fold more abundant in KYN-1 hepatoma cells than in normal liver cells. PMID- 8444315 TI - Construction of cDNA libraries from cultures of Armillaria mellea. AB - 1. Conditions were established for growth of mycelial cultures of Armillaria mellea such that the production of its lysine-specific proteinase was maximized. Proteinase synthesis was confirmed by immunoprecipitation. 2. Mycelia grown under these same conditions were used as a source of RNA and this RNA was translatable in a wheat germ translation system to produce proteins with M(r) in the range < 10,000- > 90,000. 3. Double-stranded cDNA was prepared and was inserted into the EcoR1 site of lambda gt10 and lambda gt11 using an adaptor ligation strategy. Packaging of these materials yielded large cDNA libraries. The form lambda gt10 contained 2.9 x 10(6) pfu/ml with 70% recombinants whereas that from lambda gt11 contained 2.2 x 10(6) pfu/ml with 60% recombinants. PMID- 8444316 TI - Micromethod determination of N-acetyl-alpha-D-glucosaminidase in human leukocytes and study of some of its characteristics. AB - 1. A very easy fluorescent micromethod is described to measure leukocyte N-acetyl alpha-D-glucosaminidase in human leukocytes. The method presents the following advantages: possibility to measure low activity due to prolonged linearity, very moderate consumption of substrate, use of total homogenate without the need for protein removal by precipitation after the enzyme reaction, and minimal handling after the addition of the stopping reagent. 2. A number of enzyme characteristics as linearity (up to 16 hr), pH optimum (4), thermoresistance at different temperatures (up to 24 hr at room temperature) and at different pH values (no differences between 3-8) and solubilization by digitonin and Triton X-100 were determined. The characteristics (acid pH optimum, binding to Concanavalin A and stability for prolonged time at 0 and 23 degrees C) are in agreement with the known properties of most lysosomal enzymes. 3. The specific activity of the enzyme is very low and an unexplained low latency (about 30%) was observed. PMID- 8444317 TI - Analysis of purine metabolic enzymes in human CD4 Leu 8- and CD4 Leu 8+ lymphocyte subpopulations. AB - 1. Specific activities of adenosine deaminase, purine nucleoside phosphorylase, adenosine kinase, 5'-nucleotidase, S-adenosyl-L-homocysteine hydrolase, AMP deaminase, adenine phosphoribosyl transferase, and hypoxanthine phosphoribosyl transferase were analyzed in human CD4 T-lymphocyte subsets. 2. CD4 Leu 8- (helper/inducer) and CD4 Leu 8+ (suppressor/inducer) subpopulations were obtained by panning or fluorescence activated cell sorting techniques using specific monoclonal antibodies. 3. A 45% decrease of 5'-NT AMP activity in the CD4 Leu 8- cells (suppressor/inducer) compared with CD4 total cell population. 4. No statistical significant differences in enzyme activity were found between the subsets analyzed in other purine enzymes. 5. These results suggest that the distribution of purine metabolic enzymes is homogeneous in CD4 Leu 8- and CD4 Leu 8+ T-lymphocyte subpopulations. PMID- 8444318 TI - Effect of LCAT on HDL-mediated cholesterol efflux from loaded EA.hy 926 cells. AB - 1. Human endothelial cells (EA.hy 926 line) were loaded with cholesterol, using cationized LDL, and the effect of lecithin:cholesterol acyltransferase (LCAT) on cellular cholesterol efflux mediated by high density lipoproteins (HDL) was measured subsequently. 2. In plasma, lecithin:cholesterol acyltransferase (LCAT) converts unesterified HDL cholesterol into cholesteryl esters, thereby maintaining the low UC/PL ratio of HDL. It was tested if further decrease in UC/PL ratio of HDL by LCAT influences cellular cholesterol efflux in vitro. 3. Efflux was measured as the decrease of cellular cholesterol after 24 hr of incubation with various concentrations of HDL in the presence and absence of LCAT. LCAT from human plasma (about 3000-fold purified) was added to the cell culture, resulting in activity levels in the culture media of 60-70% of human serum. 4. Although LCAT had a profound effect on HDL structure (UC/TC and UC/PL ratio's decreased), the enzyme did not enhance efflux of cellular cholesterol, using a wide range of HDL concentrations (0.05-2.00 mg HDL protein/ml). 5. The data indicate that the extremely low unesterified cholesterol content of HDL, induced by LCAT, does not enhance efflux of cholesterol from loaded EA.hy 926 cells. It is concluded that the HDL composition (as isolated from plasma by ultracentrifugation) is optimal for uptake of cellular cholesterol. PMID- 8444319 TI - Non-transferrin-bound-iron in serum and low-molecular-weight-iron in the liver of dietary iron-loaded rats. AB - 1. The feeding of 0.5% (3,5,5-trimethylhexanoyl)ferrocene (TMH-ferrocene) in rats resulted in a severe and progressive liver siderosis (total liver iron, 30 mg/g liver wet weight, after 30 weeks). 2. High concentrations of an iron-rich ferritin (up to 250 mg/l) were detected in serum of heavily iron-loaded rats forming a large fraction of non-transferrin-bound-iron (5000 micrograms/dl in maximum). 3. Ferritin and not haemosiderin was the major iron storage protein in the liver. 4. The total liver iron concentration (from 0.4 to > 30 mg Fe/g wet wt) but not the cytosolic low-molecular-weight-iron fraction (from 0.5 to 2.5 microM) was extremely increased during iron-loading. PMID- 8444320 TI - Effects of transforming growth factor-beta on collagen gene expression and collagen synthesis level in mineralizing cultures of osteoblast-like cell line, MC3T3-E1. AB - 1. High levels of type I collagen mRNA and [3H]proline incorporation into collagenase digestable protein by MC3T3-E1 cells were detected during the first 7 days of culture, after which they declined. 2. Type I collagen gene expression was stimulated by TGF-beta in the early culture stage when the collagen gene expression was fully functioning. 3. However, these stimulatory effects disappeared at the differentiation stages. Although collagen gene expression was stimulated by TGF-beta (2.0 ng/ml) in early culture, collagen synthesis in medium was not. 4. This study shows that collagen synthesis and collagen gene expression were affected by the state of differentiation in MC3T3-E1 cells and that the rate of stimulation by TGF-beta in collagen gene expression decreased over time in culture. PMID- 8444321 TI - Influence of carbicron (O-[(2-butenoic acid)-N,N-dimethylamide-3-yl] O,O dimethylphosphate) on some biochemical and biophysical parameters of rat liver membranes. AB - 1. Treatment of rats with carbicron induced a reduction of the phospholipids in both microsomal and plasma membranes. 2. A decrease of the structural order parameter (SDPH) and an increase of the pyrene excimer-to-monomer fluorescence ratio (IE/IM) was also observed, indicating membrane fluidization. 3. The specific activity of membrane-bound phospholipase A2 and phospholipase C were decreased in both types of membranes, whereas acyl-CoA:lysophosphatidylcholine acyltransferase activity was augmented due to carbicron treatment. PMID- 8444322 TI - Structural features of carbohydrate chains in human salivary mucins. AB - 1. The structure of carbohydrate chains in the low and high molecular weight mucus glycoprotein forms from submandibular-sublingual saliva of individuals with blood group B was investigated. 2. Alkaline borohydride reductive cleavage of the glycoproteins yielded in each case a population of neutral (55%) and acidic (45%) oligosaccharide alditols ranging in size from 3 to 16 sugar units. 3. The predominant neutral oligosaccharides in both glycoprotein forms consisted of 16 and 15 sugar units arranged in triantennary fashion, and carried blood group B and I antigenic determinants. 4. Three of the oligosaccharides in each glycoprotein contained sialic acid and ranged in size from 3 to 12 sugar units. In two oligosaccharides sialic acid was linked to C3 of galactose and in one to C6 of N-acetylgalactosamine. The sulfated oligosaccharide in both glycoproteins was identified as a pentasaccharide with the sulfate ester group at C6 of N acetylglucosamine. 5. The results demonstrate that contrary to the earlier view the low and high molecular weight mucus glycoprotein forms of human saliva contain identical carbohydrate chains. PMID- 8444323 TI - Isolation of a hemorrhagic toxin from the venom of Agkistrodon contortrix laticinctus (broad-banded copperhead) and pathogenesis of the hemorrhage induced by the toxin in mice. AB - 1. A hemorrhagic toxin was isolated from the venom of Agkistrodon contortrix laticinctus (Broad-Banded Copperhead) by Sephacryl S-200 HR column chromatography followed by high performance chromatography on Waters DEAE 5PW and protein Pak 125 columns. 2. Homogeneity was determined by the presence of a single band in acrylamide gel electrophoresis with silver staining. 3. ACL hemorrhagic toxin I has a molecular weight of about 29,000, is slightly acidic, and is a metalloprotease with activity towards the substrates N,N-dimethylcasein and bovine fibrinogen. Although the toxin is able to hydrolyze fibrinogen in vitro, it does not possess any defibrinogenating activity in vivo whereas the crude venom does show this activity. It has similar cleavage specificities to other snake venom hemorrhagic toxins. 4. ACL hemorrhagic toxin I causes hemorrhage of rapid onset, present within 5 min of intramuscular injection into mice, and the pathogenesis is one of hemorrhage per rhexis in which capillary endothelial cells are ruptured. PMID- 8444324 TI - Temporal and spatial parameters of gait in children. I: Normal control data. AB - A study of the spatial and temporal parameters of gait was performed on 134 normal children, 68 boys and 66 girls, aged between three and 18 years. Normal gait showed a clear asymmetry; gait was considered to be abnormally asymmetrical if differences between left and right measurements exceeded 8 to 10 per cent. In addition, there was a definite bias comparing left and right sides, which may relate to individual laterality. PMID- 8444325 TI - Temporal and spatial parameters of gait in children. II: Pathological gait. AB - Temporal and spatial parameters of gait were measured in 72 children with anomalous walking patterns as a result of neuromuscular impairment, 21 with childhood hemiplegia, 27 with congenital paraplegia and 24 with miscellaneous neuromotor disorders. Measurements were compared with those for a group of normal children. In all three groups, step length, average maximum foot-velocity and walking speed were reduced, double support time was increased, while cadence deviated from normal in both directions. Hemiplegic children varied considerably in their measured side-to-side gait asymmetries, suggesting a range of gait abnormalities not specified by subjective means alone. Measured gait parameters were significantly related to Hoffer grade of functional mobility in paraplegic children. Objective gait analysis using established temporal and spatial measurements is of clinical value in the management of childhood neuromuscular disorders. PMID- 8444326 TI - Nutrition-related growth failure of children with quadriplegic cerebral palsy. AB - Growth failure and nutritional status were evaluated in 142 children with quadriplegic cerebral palsy, aged between two and 18 years. Linear growth was assessed by upper-arm and lower-leg lengths: both means were significantly reduced. Mean bodyweight and triceps skinfold thickness fat stores were reduced to 65 per cent medians and subcapsular skinfold fat stores to 81 per cent median. Muscle stores were the most preserved and reduced to 88 per cent median. Examination of the sample by age-group showed significant reductions in growth and nutrition status indicators, even at two to four years, except for muscle area. To determine the degree to which nutritional status affected linear growth, a set of two-step regression analyses was conducted. The linear growth measures were significantly correlated with the measures of nutritional status. PMID- 8444327 TI - Neuropsychological outcome of children after radiotherapy for intracranial tumours. AB - With the aim of determining the neuropsychological disturbances associated with cranial radiotherapy in the child, a cross-sectional study was carried out on 25 survivors of medial-edge intracranial tumours. Children irradiated for intracranial tumours experienced deterioration mainly in visual attention and memory, but also in verbal fluency, full-scale IQ, and performance IQ and all its subtests, compared with control groups. This deterioration progressed with time, finally involving at least abstract thought and verbal skills. The pattern of damage by irradiation varied according to the degree of brain maturity, therefore the younger the child at irradiation, the greater the decline in IQ and visual constructive abilities, and the earlier the deterioration of visual memory and verbal skills. PMID- 8444328 TI - Psychiatric aspects of epilepsy in childhood treated with carbamazepine, phenytoin or sodium valproate: a random trial. AB - Sixty-four new cases of childhood epilepsy were randomly assigned to either carbamazepine, phenytoin or sodium valproate, and were assessed with behavioural measures before medication and after one and six months of treatment. Those treated with carbamazepine and sodium valproate had minor behavioural difficulties after a month of treatment, but these did not persist. Mothers of the epileptic children had unusually high levels of anxiety and depression two months, on average, after epilepsy was diagnosed. PMID- 8444329 TI - Central nervous system alterations in a case of short-rib polydactyly syndrome, Majewski type. AB - The authors present a case of CNS abnormalities in a female newborn infant with Majewski syndrome. On examination the gyri were found to be normal, but there was narrowing of the corpus callosum and fornix, and dilated ventricles. A vermis hypoplasia and an arachnoid cyst were found between the cerebellar hemispheres. Cross-section of the cervical and thoracic segments revealed a flattened spinal cord in the sagittal section. There were reactive astrocytes and heterotopic ganglion cells in the white matter and isolated hypoxically damaged nerve-cells in the subiculum and nuclear masses of the brainstem. These findings are discussed with reference to the literature. PMID- 8444330 TI - Transient bilateral internuclear ophthalmoplegia after minor head-trauma. AB - Following minor occipital head-trauma, a six-year-old boy developed bilateral internuclear ophthalmoplegia (INO) as the only neurological sign. After having excluded all other possible aetiological causes by careful examination, including magnetic resonance imaging, the symptoms eventually were attributed to the trauma. The course of the INO was documented by electro-oculography. A saccades training programme specially adapted to the boy's age was performed, and complete remission of the oculomotor symptoms occurred after one year. PMID- 8444331 TI - Origins of handedness in human infants. PMID- 8444332 TI - Reliability of interpretation of cranial ultrasound examinations of very low birthweight neonates. AB - The authors studied intra- and inter-reader reliability of the interpretation of cranial ultrasound examinations of very low-birthweight infants. A radiologist read 173 films, 88 of which he had read previously; the other 85 had been read previously by a second radiologist. For the diagnoses of subependymal hemorrhage and intraventricular hemorrhage, intra-reader agreement was similar to inter reader agreement. 98 ultrasound films were read initially as showing subependymal hemorrhage; in nine cases the second reading did not agree. In five of 58 cases read initially as showing intraventricular hemorrhage, the second reading did not agree. Similarly, of 32 cases read initially as showing intraparenchymal echo density, four were interpreted as negative on second reading. For all three diagnoses, disagreement occurred often enough to cause substantial misclassification bias when cranial ultrasound is used for clinical research. PMID- 8444333 TI - Clinical testing of distortion-product otoacoustic emissions. AB - Otoacoustic emissions have great promise for use in clinical tests of the functional status of outer hair cells, which represent cochlear structures that make a major contribution to the hearing process. A substantial literature is available concerning the evaluation of outer hair cell function by transiently evoked otoacoustic emissions. However, relatively little attention has been focused on the benefits of testing with distortion-product otoacoustic emissions. The purpose of this presentation is to provide knowledge of the principal advantages offered by distortion-product emissions testing. PMID- 8444334 TI - Auditory brain stem response for objective measures of hearing. AB - The auditory brain stem response (ABR) is felt to be an objective technique for predicting hearing thresholds because a voluntary response is not required from the subject. However, determination of ABR threshold can be a subjective process. This article discusses a technique, termed Fsp, which adds objectivity to ABR threshold detection by creating a ratio of signal plus averaged background noise over an estimate of the averaged background noise for any given averaged ABR. Fsp values have an F distribution. Consequently, the confidence of true detection for a given ABR can be determined by comparing its calculated Fsp value to statistical tables. Using a technique such as Fsp not only adds objectivity to ABR threshold detection, but also optimizes test time by allowing the averaging process to stop as soon as the background noise has been reduced and the true neural potential can be judged to be present. The estimate of the background noise can be used as a weighting factor to reduce the influence of noisy segments during the averaging process as well. Using this technique, we have found ABR threshold to be within 5 or 6 dB of psychophysical threshold for like (click) stimuli and, in our pediatric clinic, ABR click thresholds are within 10 dB of puretone average for children with losses ranging from mild to profound. PMID- 8444335 TI - Detection of hearing impairment with the acoustic stapedius reflex. AB - The acoustic stapedius reflex (ASR) is the sound-evoked contraction of the stapedius muscle. The ASR is mediated by a neural network, receiving its afferent input from the VIIIth cranial (auditory) nerve and sending its efferent output to the VIIth cranial (facial) nerve. Several centers in the brain stem comprise the central portion of the reflex pathway. The stapedius muscle in each ear responds to ipsilateral, contralateral, and binaural stimulation. The normal ASR threshold is 90 to 95 dB SPL for tones and 70 to 75 dB SPL for wideband noise. In ears with sensorineural hearing loss, ASR thresholds are elevated more for wideband noise than for tones. These bandwidth-related changes form the basis for detection of hearing loss from ASR data. A number of methods have been proposed which differ in the nature of the outcome. Some try to quantitatively estimate hearing loss, whereas others categorize outcomes as pass or fail. In general, methods that attempt quantitative estimation of hearing loss do so at the expense of higher error rates. With adequate recording techniques, the ASR has been shown to effectively detect hearing losses exceeding 30 dB in adult subjects. Although ASR recording in newborns requires a higher probe frequency than the commonly used 226 Hz, ASR thresholds in newborns appear to be similar to those in adults. Limited information exists on the use of the ASR for detection of hearing loss in the infant population. With adequate attention to methodological requirements of testing infants, the ASR may offer a cost-effective method for the early detection of hearing loss. PMID- 8444336 TI - Objective response detection. AB - Evoked potential threshold estimation can be made truly objective by using statistically based methods. In general, time domain analysis is preferable for responses which are impulsive (temporally narrow, spectrally broad), whereas frequency-domain analysis is more appropriate for tonal responses (spectrally narrow, temporally broad). In both time and frequency domains, methods comparing evoked potential power to noise models are robust and powerful. For spectrally narrow responses such as steady-state evoked potentials, the performance of magnitude-squared coherence, the ratio of grand average power to mean subaverage power, is superior to that of other methods for objective response detection. PMID- 8444337 TI - Clinical implications of primary and nonprimary pathway contributions to the middle latency response generating system. AB - Clinical use of the middle latency response (MLR) has been limited by the variability of the response during sleep in young children. Theoretically, this variability can be explained by the differential maturation of the primary and nonprimary components of the MLR generating system. The model is supported by animal neurophysiological data. Applied to the human system, the model predicts that, in children, MLR generators are active only during certain stages of sleep. From a clinical standpoint, this has led to a procedure for signaling the clinician when a child is in a sleep state favorable for recording the MLR. PMID- 8444338 TI - Adding objectivity to infant behavioral audiometry. AB - This article deals with the limitations of infant behavioral audiometry, which have led us to seek objective methods of audiometry for determining hearing sensitivity in infants. It describes efforts to add objectivity to (or reduce the subjectivity of) behavioral methods of infant audiometry. Several aspects of visual reinforcement audiometry (VRA), including the head turn response, the use of control trials, and adherence to the principles of operant conditioning, serve to reduce the subjectivity inherent in behavior observation audiometry. In addition, computer control of VRA procedures can relieve the examiner of potentially subjective decision-making during the course of evaluation and can facilitate testing with sophisticated algorithms that could not be done manually by a single examiner. Computer simulations to determine the best VRA test parameters are described. PMID- 8444339 TI - Objective electrophysiological measures from cochlear implant patients. AB - Various objective electrophysiological techniques have been used to supplement the behavioral measurements for cochlear implant patients. This report summarizes various studies of these measurements, including stimulus artifact, averaged electrode voltages, electrical stapedius reflexes, electrical auditory brain stem responses, electrical middle latency responses, and cortical auditory responses. These techniques have been shown to provide valuable information in the evaluation of device and electrode integrity in addition to correlated values to behavioral thresholds and comfort levels. PMID- 8444340 TI - Characterisation of the gene encoding an unusually divergent TATA-binding protein (TBP) from the extremely A+T-rich human malaria parasite Plasmodium falciparum. AB - The intergenic regions of the human malaria parasite, Plasmodium falciparum, are extreme in their base composition, averaging approx. 90% A + T. As a first step to investigating whether transcription in this organism follows conventional models based largely on yeast, we have isolated and characterised the gene (TBP) encoding its TATA-binding protein (TBP). The gene is present as a single copy on chromosome 5 and is expressed as a 1.8-kb mRNA encoding a protein of 228 amino acids (aa) (26 164 Da). The inferred protein product has a bipartite structure consisting of a 45-aa species-specific N-terminal domain and a 183-aa C-terminal domain. In the latter, the malarial protein contains two directly repeated, but imperfectly homologous regions, each approx. 78 aa in length, together with a highly basic region located between them. These features are characteristic of all TBPs studied to date. Moreover, hydropathy plots suggest that the overall folding of this C-terminal domain is very similar to that of other TBPs. However, TBP from P. falciparum is much less closely related at the primary sequence level to the archetypal yeast homologue than are all other characterised TBPs (42% identity, compared to 76-93%, respectively). Despite this divergence of the primary sequence, most residues known to be involved in DNA binding are conserved. Those instances where sequence variation at generally conserved residues is observed may reflect functional differences that could ultimately be exploited by selective chemotherapy. PMID- 8444341 TI - Mutational analysis of the transforming and apoptosis suppression activities of the adenovirus E1B 175R protein. AB - The role of the adenovirus-2 E1B 19-kDa (175R) T antigen in E1a-cooperative transformation was determined by cotransfection of plasmids expressing E1A or E1B 175R T antigens into primary rat kidney (BRK) cells. Transformed cells were selected by virtue of their resistance to the antibiotic Geneticin (G418) conferred by neo gene co-expression from plasmids coding for 175R. 175R cooperated efficiently with genomic E1a and specifically with the 289R protein coded by the 13S mRNA in the transformation of primary BRK cells. Mutational analysis of the 175R protein revealed that the N terminus and the C-terminal 30 amino acids are not essential for E1a-cooperative transformation. Several conserved sequences located in the middle of the 175R protein are essential for transformation. The effect of various mutants to suppress apoptosis (programmed cell death) induced by an anti-cancer agent, cisplatin, was examined in cells producing the E1A and E1B 175R proteins. Apoptosis was measured by flow cytometric analysis and indicates that the 175R protein efficiently prevents cisplatin-induced apoptosis. This suggests that the 175R function involved in transformation segregates with its ability to suppress cisplatin-induced apoptosis. PMID- 8444342 TI - The dhod gene and deduced structure of mitochondrial dihydroorotate dehydrogenase in Drosophila melanogaster. AB - We have carried out experiments to determine the structural organization of dhod and its apparent dihydroorotate dehydrogenase (DHOdehase) product. Germline transformation with dhod genomic DNA sequences permitted assignment of the functional limits of the gene to a 5-kb region, providing an experimental system for detailed analysis of this gene, as well as the DHO dehase protein. As expressed in embryos, the gene is a simple transcriptional unit containing two exons totalling 1347 nucleotides (nt) and a single small 5' intron of 54 nt. Compared to the enzyme from microorganisms, the deduced DHOdehase protein of 405 amino acids shows strong similarities within the presumptive catalytic portions of the protein. However, the N-terminal portions of these proteins are highly dissimilar, presumably reflecting diversity in the intracellular localization of DHOdehase in the different organisms. The Drosophila melanogaster protein contains N-terminal sequences that are typical of other mitochondrial intermembrane space proteins in animal cells. PMID- 8444343 TI - The gene encoding chicken chromosomal protein HMG-14a is transcribed into multiple mRNAs. AB - The sequence and structure of the chicken HMG14a gene encoding HMG-14a non histone chromosomal protein suggest that it may be a unique member of the HMG (high mobility group) gene family with properties intermediate to those of the typical HMG-14 and HMG-17 genes. Genomic clones were isolated which together contain the complete chicken HMG-14a gene. The gene covers about 10 kb while coding for an mRNA of about 1000 nt in size. Primer extension, S1 mapping and further cDNA clone analysis suggest that HMG-14a codes for multiple mRNAs arising from two or more transcription start points with alternative splicing and utilization of two or more polyadenylation sites. However, no variation in the coding portion of the mRNA has been observed. The sequence of the promoter region of HMG-14a is similar to that of chicken HMG-14b and human HMG-14 in that it is very G+C rich, contains several putative Sp1-binding sequences and has an unusually high density of CpG dinucleotides. Expression studies confirm earlier results suggesting that the gene is expressed at low levels in most tissue types. PMID- 8444344 TI - Cloning and characterization of a novel zinc-finger protein-encoding cDNA from the mouse eye lens. AB - Zinc fingers (Zf) are a common structural motif found in many nucleic acid binding proteins. In an effort to identify potential transcription factors in the mouse eye lens, we have isolated a Zf-containing clone from a newborn mouse lens cDNA library. The clone, named pMLZ-4, is 4.5 kb in length and contains an open reading frame of 1073 bp. The putative pMLZ-4 protein consists of a short, N terminal acidic domain followed by twelve tandemly arrayed Zf of the C2H2 variety. The remaining 3.2 kb of the cDNA comprises the 3'-untranslated region. PCR analysis detected the presence of pMLZ-4 RNA in liver, heart, kidney, spleen and brain of newborn mice. Hybridization of pMLZ-4 to genomic DNA from a number of species of vertebrates revealed the presence of homologous sequences only in mouse and rat. Unexpectedly, the probe also hybridized to a single band in yeast DNA digested with EcoRI. NIH3T3 cells were stably transformed with a construct that over-expresses the pMLZ-4 mRNA. The stably transformed cells did not differ in appearance from untransformed cells, and an analysis of proteins from transformed and untransformed cells failed to detect any differences resulting from over-expression of the pMLZ-4 mRNA. PMID- 8444346 TI - Allele-specific activation of the c-myc gene in an atypical Burkitt's lymphoma carrying the t(2;8) chromosomal translocation 250 kb downstream from c-myc. AB - The genetic structure and regulation of the c-myc gene was comprehensively studied for the first time in Burkitt's lymphoma with t(2;8) translocation. In a Burkitt's lymphoma cell line, KOBK101, the immunoglobulin kappa-encoding gene on chromosome 2, accompanied by its enhancer, was translocated to the pvt-1 locus located about 250 kb downstream from c-myc on chromosome 8. Only the c-myc allele on the translocated chromosome carried aberrant SalI and KpnI sites in the first intron, so the two c-myc alleles and their transcripts were analyzed separately. The c-myc allele on the untranslocated chromosome conserved the normal c-myc sequence and was transcriptionally silent. In contrast, the c-myc allele on the translocated chromosome was actively transcribed at three- to fivefold higher levels, as compared with non-malignant B-cell lines. Additionally, it carried predominant multiple mutations consisting of 64 nucleotide substitutions, three short deletions, and a one-base insertion, most of which clustered in the first exon and intron. The 24-base deletion in the first intron completely overlapped the binding site of a putative negative transcriptional factor of the 138-kDa phosphoprotein, MIF. Thus, the multiple mutations and the deregulated, allele specific expression of c-myc were associated with the chromosomal translocation in cis. Together activation by the long-distance immunoglobulin kappa enhancer, and the alleviation of negative regulation by the mutations, seemed to cause the allele-specific activation of c-myc. PMID- 8444345 TI - Isolation of the CCAAT transcription factor subunit EFIA cDNA and a potentially functional EFIA processed pseudogene from Bos taurus: insights into the evolution of the EFIA/dbpB/YB-1 gene family. AB - The genomic copy multiplicity of the CCAAT transcription complex component enhancer factor I subunit A (EFIA) has been examined. When a mammalian genomic Southern blot was hybridized to a rat EFIA cDNA, a complex pattern consisting of numerous related sequences was found in all the species examined, with Bos taurus being the least complex. An EFIA#1 cDNA from Bos taurus was isolated from a primary lung endothelial cell cDNA library by screening with the 1489-bp rat EFIA cDNA. The deduced bovine EFIA#1 amino acid (aa) sequence is 98% identical to rat EFIA and 100% identical to human EFIA/DbpB/YB-1 family member DNA-binding protein B (DbpB). In addition, a processed EFIA pseudogene from Bos taurus, designated bovine psi EFIA#1, was obtained from a genomic library by screening with a rat EFIA cDNA probe. The bovine psi EFIA#1 gene has an ORF which, if expressed, would encode a 140-aa sequence, with aa 31-140 having 84% identity to bovine EFIA#1. The genomic cloning data indicate that processed pseudogenes are partially responsible for the complexity of the EFIA genomic Southern blots. The phenomenon of 'repeat induced point mutation' (ripping) at bovine psi EFIA#1 gene CpG dinucleotides occurs at a 6.5-fold higher frequency than expected from random mutagenesis. Therefore, ripping is likely to be the mechanism by which the bovine EFIA#1 pseudogene's ectopic recombination potential was inactivated. PMID- 8444347 TI - Characterization of the gene encoding alpha-sarcin, a ribosome-inactivating protein secreted by Aspergillus giganteus. AB - The filamentous fungus, Aspergillus giganteus, produces the extracellular ribosome-inactivating protein, alpha-sarcin (Sar). The structural gene (sar) encoding Sar was isolated and characterized by sequence analysis and expression in Aspergillus niger. It codes for a precursor of 177 amino acids containing a secretion signal sequence that is absent in the mature protein. The nucleotide sequence contains several typical features of fungal genes, including a short intron of 65 bp. The transcriptional and translational processing signals of the gene are functional in A. niger, but the yield of recombinant protein is low in comparison with the natural producer. A comparison of sar with the gene encoding restrictocin from Aspergillus restrictus revealed a high degree of similarity between both genes. The conservation of the aa sequence suggests that Sar-like proteins may confer a selective advantage to these fungi under certain environmental conditions. PMID- 8444348 TI - Cloning and characterisation of the gene encoding the 28-kDa glutathione S transferase of Schistosoma mansoni. AB - The 28-kDa glutathione S-transferase (GST) of Schistosoma mansoni is considered a possible vaccine candidate for use against this medically important parasite. The gene encoding this molecule has been isolated from a lambda EMBL4 library by using the corresponding cDNA sequence as a probe. The gene contains four exons and is approximately 5.5 kb in length. Analysis of the 5' flanking region revealed the presence of a consensus AP-1 recognition site, 5'-TGACTCA, between nucleotides -231 and -225. Southern blot analysis suggested the presence of a single gene encoding the 28-kDa GST in the S. mansoni genome. PMID- 8444349 TI - Cloning and characterization of a plant gene encoding a protein kinase. AB - The cloning and sequence analysis of a gene that encodes a homologue of protein kinase (PK) from Arabidopsis thaliana is reported. We screened a genomic DNA library of A. thaliana using as probes oligodeoxyribonucleotides or fragments from the polymerase chain reaction that correspond to conserved regions in the catalytic domains of various PKs. One genomic clone, named Atpk5, was sequenced and analyzed. Transcripts of the corresponding gene, Atpk5, were detected in root, leaf and flower tissues by Northern blot analysis. The deduced amino acid sequence of the putative product of Atpk5 resembles those of kinases that phosphorylate ribosomal protein S6, cAMP-dependent PKs and protein kinase C. From the results of sequence comparisons, the ATPK5 protein appears to be a member of a subfamily of Ser/Thr-PKs specific to plants. PMID- 8444350 TI - Structure of the rudimentary-like gene and UMP synthase in Drosophila melanogaster. AB - The last two steps of de novo UMP biosynthesis are performed by a bi-enzymic protein in animal cells, UMP synthase, that is encoded by the gene r-l in Drosophila melanogaster. Over 3.5 kb of genomic DNA spanning this gene were sequenced. Transcriptional organization of r-l has been determined by sequence analysis of two cDNA clones and by primer extension analysis of embryonic RNA. The DNA region 5' to the apparent transcription start point contains no known transcriptional control elements or sequences similar to those upstream from dhod, which encodes the metabolic pathway step preceding UMP synthase. The deduced protein of 53.5 kDa is similar to the UMP synthases of slime molds and humans. It contains the two enzymatic domains separated by an apparent bridge polypeptide sequence of over 30 amino acids, which is dissimilar among UMP synthases of different organisms. The r-l structure includes two introns, one of which occurs within the DNA region that encodes the interdomain bridge sequence of the protein. PMID- 8444351 TI - Use of DNA end joining activity of a Xenopus laevis egg extract for construction of deletions and expression vectors for HIV-1 Tat and Rev proteins. AB - We have developed a cloning strategy which combines conventional T4 DNA ligation with the highly efficient nonhomologous DNA end joining (EJ) activity of an extract from Xenopus laevis eggs. The nonhomologous EJ activity allowed the rapid construction of deletion mutants by the intramolecular rejoining of nonhomologous DNA ends generated for the purpose of deleting restriction fragments from the vector. The combined use of T4 DNA ligase for intermolecular ligation and X. laevis egg extracts for intramolecular nonhomologous EJ proved to be a powerful tool, as demonstrated here for the construction of expression vectors for HIV-1 Tat and Rev. PMID- 8444352 TI - PCR cloning and sequence of two cDNAs encoding the alpha and beta subunits of rabbit casein kinase-II. AB - Polymerase chain reaction (PCR) amplification of total RNA from vascular smooth muscle cells (VSMC) was used to clone and sequence full-length cDNAs encoding the alpha and beta subunits of rabbits casein kinase-II (CK-II). A strong homology and evolutionary conservation was found in both the nucleotide (nt) and deduced amino acid sequences of CK-II from various species, with up to 100% identity among vertebrate homologues and 88% and 64% identity on the nt level with Drosophila melanogaster and yeast, respectively, compared with rabbit CK-II. The cloning and expression of rabbit CK-II will allow us to generate antibody and cDNA probes to investigate the role of CK-II in VSMC growth, migration, and phenotypic transformation during the pathogenesis of vascular disease. PMID- 8444353 TI - Cloning and sequencing an ovine interleukin-4-encoding cDNA. AB - We have cloned a cDNA containing the complete coding sequence of ovine(ov) interleukin 4 (IL4) by the polymerase chain reaction using primers based on the 5' and 3' untranslated regions of the human IL4 gene. RNA was isolated from phorbol myristate acetate- and calcium ionphore A23187-stimulated mesenteric lymph node cells. The ovIL4 cDNA is 535 bp in length and contains an open reading frame of 408 nucleotides (nt) coding for a 15.1-kDa IL4 precursor of 135 amino acids (aa). Cleavage of the putative signal peptide of 22 aa yields the mature form of 13.2 kDa. Analysis of the mature aa sequence shows two potential N-linked glycosylation sites and six Cys residues. Ovine and bovine IL4 are shorter than human, mouse and rat IL4, because of a 51-nt deletion in the coding region. Comparison of the predicted aa sequence shows that ovIL4 shares 92, 57, 37 and 42% identity with the bovine, human, mouse and rat IL4s, respectively. PMID- 8444354 TI - An Alu sequence interrupts a human 5-hydroxytryptamine1D receptor pseudogene. AB - Molecular cloning studies have now identified six HTR genes encoding the biosynthesis of the structurally homologous human serotonin (5-hydroxytryptamine; 5-HT) receptors, namely 5-HTR1A, 5-HTR1B, 5-HTR1C, 5-HTR1D, 5-HTR2 and 5-HTRS31. Several of these receptors are encoded by intronless genes, and we now report the cloning of another intronless serotonergic HTR gene. This gene was cloned by a method using the polymerase chain reaction. The nucleotide sequence of this gene is most closely homologous to the 5-HTR1D gene; however, several stop codons, frame shifts and deletions are present in the coding region suggesting that this is a pseudogene which could not encode a functional receptor. Sequence analysis also revealed that the coding sequence of this pseudogene is disrupted by insertion of a 283-bp Alu repeat sequence. PMID- 8444355 TI - Novel CDC2-related protein kinases produced in murine hematopoietic stem cells. AB - The polymerase chain reaction with degenerate primers was used for the amplification of cDNA encoding CDC2-related protein kinase (PK) sequences from murine hematopoietic stem cells. In total, nine different PK-encoding sequences were obtained. At least four of them encode previously unknown PKs. PMID- 8444356 TI - Sequence of the cDNA encoding bovine uridine monophosphate synthase. AB - A 1869-bp cDNA encoding bovine UMP synthase (UMPS), including the 3'-untranslated and 34 bp of the 5'-untranslated regions, was isolated and sequenced. The deduced amino acid sequence shows a high degree of homology to UMPS sequences reported from other species, namely for regions corresponding to the putative catalytic sites. The sequence information will be used to analyse the molecular basis of the deficiency of UMPS (DUMPS) in cattle. PMID- 8444358 TI - Intraocular and plasma kinetics of tenoxicam in rabbits. AB - Non-steroidal anti-inflammatory drugs (NSAID) represent potentially useful agents in the treatment of a number of ocular pathologies, but their intraocular penetration and distribution have not yet been reported. With the aim of clarifying this point, we evaluated the concentrations of the well known NSAID, tenoxicam, in the aqueous and vitreous humors of rabbits treated i.m. with the drug (7 mg/kg). The tenoxicam kinetics in these ocular fluids followed that in plasma with the time-to-peak shifted to higher values in the vitreous (1 h) as compared to that in the aqueous and plasma (40 min). AUC was also higher in the vitreous (10.4 micrograms.h/ml) than in the aqueous humor (2.8 micrograms.h/ml). PMID- 8444357 TI - Corticosteroids and daunomycin in the prevention of experimental proliferative vitreoretinopathy induced by macrophages. AB - An experimental model of proliferative vitreoretinopathy (PVR) induced by macrophages simulates a special form of wound healing process in the eye and mimics the development of PVR from its initial stage. We used this model for the evaluation of drug efficacy in the prevention of PVR. One mg triamcinolone acetonide (TA), 10 micrograms daunomycin-liposome (DL), 5 micrograms free daunomycin (FD) and 0.1 ml saline or empty liposomes (as controls) were injected into the vitreous in four groups of animals (30 or 40 rabbit eyes each) after macrophage injection. Retinal detachment developed in 77.5% of the control eyes on day 28, compared to 13.3% of the TA-treated eyes (P < 0.01), to 33.3% of the eyes treated with DL (P < 0.01), and 50% of the FD-treated eyes (P < 0.05). TA cleared up from the vitreous within 35-63 days (average 45.5 days). The half-time of FD clearance was 145.5 min. Although DL declined rapidly during the first 2 days, there was an average of 0.64 microgram/ml daunomycin in the vitreous on day 14. Transmission electron microscopy showed that FD at a dosage of over 5 micrograms or DL over 20 micrograms was toxic to the retina and that up to 4 mg TA was nontoxic. These results suggest that steroids such as TA, given at the inflammatory stage, can effectively and safely prevent the development of PVR, and that encapsulation in liposomes of cytotoxic agents such as daunomycin can enhance drug efficacy and reduce toxicity. The time course of initiation and development of PVR is important in the selection of particular drugs. PMID- 8444360 TI - Diffusion of immunoglobulins into rabbit cornea after subconjunctival injection: experimental demonstration and mathematical model. AB - To determine whether immunoglobulins of the IgG class diffus up to the corneal center after subconjunctival injection, rabbits were injected with fluorescein isothiocyanate-labeled human IgG. The inoculum diffused from the entire periphery centrepetally towards the corneal center. The progression of the diffusion front slowed down as the distance to the limbus increased. The first increase of fluorescence in the corneal center was observed on day 6. The intensity increased during the following 10 days despite resorption in the corneal periphery due to the flow of IgG from paracentral toward central areas. The diffusion coefficient of 0.003-0.004 cm2/day was calculated by computer simulation using Fickian diffusion equations adapted for corneal geometry. We conclude that after subconjunctival application, IgG diffuses up to the corneal center with a delay of several days and that the penetration speed decreases as the distance to the limbus increases. This kinetics contributes to our understanding of the role of IgG in corneal pathology and may help to design therapeutic schedules for immunotherapy with IgG. PMID- 8444359 TI - Interferon-alpha 2b inhibits proliferation of human Tenon's capsule fibroblasts. AB - To evaluate the potential of interferon-alpha 2b (IFN-alpha) as an antifibrotic treatment after glaucoma filtering surgery, we studied its ability to inhibit mitogen-induced proliferation of human Tenon's capsule fibroblasts in vitro, as shown by [3H]-thymidine incorporation. IFN-alpha inhibited fetal calf serum induced proliferation in a dose-dependent manner in concentrations ranging from 10 to 10,000 IU/ml (P < 0.001). Inhibition was also found when IFN-alpha was added prior to the mitogen (P = 0.001); this inhibitory effect lasted at least 3 days. We suggest that IFN-alpha deserves further evaluation as a possible agent for the control of ocular fibrosis. PMID- 8444361 TI - Preoperative prism correction in patients with acquired esotropia. AB - We performed a prospective study of preoperative prism adaptation in 77 patients with acquired esotropia. Sixty-three of them increased their angle of squint when wearing Fresnel press-on prisms for 5-7 days. After the angle had stabilized to a point that did not exceed the press-on prisms by more than 10 prism D, they were randomly divided into two groups. Thirty-two patients underwent surgery based on the prism-adapted angle. The other 31 patients underwent surgery based on their initially measured angle. Fourteen patients who did not respond to prism correction underwent surgery based on the angle before prism correction. Success rates with deviations between 0 and 10 prism diopters measured 1 year after surgery were highest in those in whom surgery was based on the prism-determined angle and were lowest in the nonresponders, who had no fusion response to the prisms. PMID- 8444362 TI - Pseudo-Graefe's sign: a manifestation of aberrant regeneration of the fourth cranial nerve? AB - The phenomena involved in paradoxical upper lid retraction have been observed during recovery from paralysis of the third cranial nerve (CN). One of these phenomena is pseudo-Graefe's sign or Fuch's sign, which is characterized by elevation or retraction of the upper eyelid when the eye is looking downwards and inwards. This synkinesis is caused by an aberrant regeneration of newly formed axons of the third CN that subsequently reach muscles not originally connected with them. Pseudo-Graefe's sign may occur after congenital or acquired diseases. Acquired forms occur more frequently and result from paralysis of the third CN following various intracranial diseases: aneurysms, traumas and tumors. PMID- 8444363 TI - Distinct patterns of spatial frequency response by normal, recovered optic neuritis, and normal fellow eyes to a new linearly variable neutral density device. AB - Upon apparent recovery from optic neuropathy, structural damage to the optic nerve may remain while usual measures of visual function appear normal. To test for such damage, the logarithm of optical density to cause a pattern to disappear is read directly on the scale of our device. Patients in the first study observed the disappearance of a red Amsler grid; this Threshold Amsler Score, used jointly with acuity scores, separates normal eyes from eyes with optic neuropathies. Patients in the second study used the device to measure the disappearance of the highest contrast Vistech patterns to show that this device, used over a range of spatial frequencies, differentiates "subclinical" neuropathies (recovered optic neuritis eye; never symptomatic fellow eye to a diagnosed eye) from normal eyes. This device may measure the functional photopic brightness of the stimulus pattern; when the score from our device is higher, the range of photopic brightness for the stimulus is wider, and the retina is more sensitive to contrast. PMID- 8444365 TI - Automated detection and quantification of retinal exudates. AB - Retinal exudates are a common manifestation of vascular damage in a variety of retinal diseases. We have used computerized image analysis to detect and measure the area of exudates from digitized colour fundus slides of patients with diabetic retinopathy and have assessed the repeatability, reproducibility, and accuracy of the technique. The analysis was entirely independent of the operator apart from choice of the region to be analysed. The coefficient of variation for repeatability was between 3% for large areas of exudate and 17% for small areas of exudate. The reproducibility was also within this range. Sensitivity was between 61 and 100% (mean 87%). False-positives were observed in 5 of 30 regions analysed, and these could have been eliminated by using more stringent criteria for selection of images for analysis. Time taken for the analysis was approximately 3 min. PMID- 8444364 TI - Utility of the color pattern-electroretinogram (PERG) in glaucoma. AB - Pattern-onset electroretinograms (PERGs) with red-green color contrast (CC) and green-"black" luminance contrast (LC) stripe patterns (0.3 c/deg) were recorded in a group of 80 control subjects and in a group of 42 patients having glaucomas of varying etiology and severity. The PERG data were correlated with the results of static perimetry and optic disc morphometry. In the glaucoma group the PERG was reduced significantly and by relatively similar amounts with both CC and LC stimuli. A significant correlation of the PERG reduction with visual field loss was found only with the CC, not with the LC PERG. Correlations between PERG amplitudes and neuroretinal rim areas of the optic disk were similar for the LC and for the CC stimulus. The rather poor percentage of correct classification of controls and patients based on the PERG or the optic disc morphometry alone can be improved by two-dimensional discriminant analysis using both CC PERG and papillometry data. PMID- 8444366 TI - Immunohistology of eye muscle in idiopathic orbital inflammatory disease (pseudotumor), Graves' ophthalmopathy and healthy controls. AB - Inflammatory orbital disease can be triggered by a variety of causes. Two such diseases are pseudotumor orbitae and Graves' ophthalmopathy, and both involve extraocular muscles. Biopsies were obtained from ocular muscles during a quiet phase in these two diseases. Biopsies obtained from a previous pseudotumor orbitae showed complement deposits and increased expression of HLA class-I antigens in the intermuscular tissue. The biopsies from two out of four pseudotumor cases and two out of four Graves' ophthalmopathy cases contained increased numbers of intermuscular HLA class-II-expressing cells. In spite of clinical remission, the local condition in all four pseudotumor cases and in two out of four cases of Graves' ophthalmopathy still suggests active inflammatory disease. PMID- 8444367 TI - Dilemmas of disclosure to patients and colleagues when a therapist faces life threatening illness. AB - This article highlights dilemmas imposed by disclosure and nondisclosure of a therapist's life-threatening illness to patients and colleagues. Literature is reviewed that illustrates a spectrum of circumstances and opinions, contrasting survivable with more complex or likely nonsurvivable conditions. In the case of a therapist's life-threatening illness, consultation regarding its effects on the treatment framework is appropriate and may include-while the therapist can still be a full participant in both processes-planning for both the continuity of patients' treatment and at times practice closure. This sensible, professional approach recognizes the patients' needs in the mourning process. PMID- 8444368 TI - The trade-offs of developing a case management model for chronically mentally ill people. AB - This article addresses the role of case management in the care of chronically mentally ill people. Trade-offs often occur because case management is frequently used to achieve the conflicting goals of reducing service use costs and raising the quality of life for clients. Despite these trade-offs, case management can be effective if it is designed so that services match client needs and the costs of services are measured accurately. Case management for chronically mentally ill people is particularly difficult to design because their level of functioning and need for intensive services are such that the cost to deliver the appropriate services is great. The profit-maximizing nature of the U.S. health care system makes some form of capitation likely in the design of case management services for this population. PMID- 8444369 TI - Decision making and social work: another look. PMID- 8444370 TI - Influences on social work time expenditure in a voluntary inpatient psychiatric unit. AB - This article describes a study of social work time expenditure on a voluntary inpatient psychiatric unit in an inner-city, tertiary-care, teaching hospital that serves many publicly funded patients. The study examined the influence of a number of presenting problems, individual psychosocial factors, and demographic factors. Controlling for patient length of stay, four factors were found to influence time expenditure: (1) greater number of assessed psychosocial problems, (2) Asian ethnocultural background, (3) the interactive effect of being a Medicaid recipient or having a pending Medicaid application and needing placement in a structured living situation, and (4) referrals to child protective services. PMID- 8444371 TI - The socioemotional needs of elderly family practice patients: can social workers help? AB - This study investigates the psychosocial characteristics of a group of suburban elderly people who were believed to use the relationship with their family physician for reassurance, support, and other socioemotional needs. These patients presented minor complaints, demanded time and attention, and were somewhat frustrating to their doctors. Thirty-four physicians in five New Jersey practice settings assessed elderly patients who visited their offices during a two-year period. Background data were collected on the physicians, and 193 elderly patients were interviewed. Based on pretested criteria, patients were divided into a study and comparison group. When tests were used to analyze the data, the patients with socioemotional concerns were found to be significantly more anxious, more depressed, and more introspective, and they perceived themselves to be sicker than other elderly patients. These findings have implications for the use of social workers in the service of emotionally distressed family practice patients. PMID- 8444372 TI - Functions of an adult sickle cell group: education, task orientation, and support. AB - Although psychosocial concerns of patients with sickle cell disease have been described, these descriptions are based primarily on experience with adolescents and children. In addition, there is an absence of reports on sickle cell groups specifically designed for adult patients. This article reports on the development of an adult sickle cell support group and provides a description of the psychosocial factors most prevalent in patients' lives. Major adjustment difficulties for group members included increasing anxiety about death, the disruption of their social support network, disability, dependence on pain medication, and conflicts with health care providers. This community-based support group enhanced participants' knowledge about sickle cell disease, improved the physician-patient relationship, and helped resolve psychosocial adjustment problems. PMID- 8444373 TI - Disagreements in discharge planning: a normative phenomenon. AB - The process of discharge planning is often impeded by disagreements among family members and others involved. A discharge plan must be negotiated to meet the varying needs of participants within the context of regulatory and organizational mandates. Under such circumstances, disagreements in decision making can be anticipated, particularly for family members, who must readjust roles and relationships in the face of the crisis of illness. Support for this conceptual formulation is found in the literature, particularly in two studies that evaluated the incidence of disagreements in discharge planning caseloads. In both studies, disagreements occurred in at least one-third of the cases, with most disagreements involving family members. Neither study found substantial disagreement among professionals. Social workers who provide discharge planning services in hospitals clearly are dealing with substantial levels of disagreements among principals in the process; in fact, disagreement needs to be accepted as a normative phenomenon in such planning. This article discusses the sources of family disagreements related to discharge planning, identifies the implications for social work practice, and uses a family systems perspective to articulate an approach to intervention. PMID- 8444375 TI - Canadian and American health care: myths and realities. PMID- 8444374 TI - School-based clinics: a response to the physical and mental health needs of adolescents. AB - School-based clinics staffed by an interdisciplinary team of health care professionals, including social workers, are among the pioneering efforts that address both the health and education needs of adolescents. Initial research and publications about this concept of health care service delivery have focused on the area of reproductive health; however, it is necessary to broaden the knowledge base by examining the range of problems experienced by students using the clinics. To provide data on this issue, a study was conducted in four school based health clinics in a large midwestern city. The results of this study document the use of the clinic for multiple issues and provide statistical support for the clinical impressions of the staff that students, despite their stated reason for visiting the clinic, were equally likely to have other physical and mental health problems. PMID- 8444376 TI - The special caretakers program: a hospital's solution to the boarder baby problem. PMID- 8444377 TI - [Calcitonin gene-related peptide and neural control of vascular tone]. AB - Rat mesenteric resistance blood vessels are innervated by nonadrenergic, noncholinergic (NANC) vasodilator nerves. In vitro pharmacological, biological and immunohistochemical studies have provided evidence that the calcitonin gene related peptide (CGRP), a 37 amino acid peptide translated by the calcitonin gene, has a potent vasodilator effect and acts as a vasodilator neurotransmitter for NANC vasodilator nerves. The CGRP-containing vasodilator nerves inhibit adrenergic nerve-mediated vasoconstriction through direct relaxation of vascular smooth muscle, while adrenergic nerves suppress the neurotransmision of CGRP containing nerves by inhibiting CGRP release from the nerve. Thus, CGRP containing nerves and adrenergic nerves control vascular tone with reciprocal interferences. In in vivo studies, spinal cord (T9-12) stimulation of pitched rats produced a NANC depressor response mediated by endogenous CGRP, suggesting that CGRP-containing nerves are regulated by the central nervous system. The malfunction of CGRP-containing vasodilator nerves may be involved in cardiovascular diseases such as essential hypertension, coronal vasospasm, cerebral vasospasm and Renaud's phenomenon. It is suggested that the CGRP containing vasodilator nerves play an important role in the regulation of vascular tone. PMID- 8444378 TI - [Effect of Y-25130 on gastric motility in anesthetized rats]. AB - We developed an automatic analyzing system using a personal computer to evaluate gastric motility objectively. Gastric motility was divided into three elements: motility index, amplitude and frequency. These elements analyzed with both computer and manual methods closely correlated with each other (R2 = 0.943, 0.985 and 0.986, respectively). The effect of Y-25130 on gastric motility was investigated in anesthetized rats with the automatic analyzing system. Intravenous administration of Y-25130 increased both spontaneous and cisplatin reduced gastric motility. The effect of Y-25130 on spontaneous motility was superior to that of ondansetron and metoclopramide, and the effect on cisplatin reduced motility was almost the same as that of ondansetron and superior to that of metoclopramide. In vagotomized rats, Y-25130 did not increase the gastric motility not only in spontaneous conditions but also in efferent vagus stimulated conditions. Atropine completely blocked the gastric motility induced by Y-25130. In capsaicin pre-treated rats, Y-25130 had no effect. On the other hand, Y-25130 increased the gastric motility induced by afferent vagus stimulation. These results suggest that Y-25130 increases gastric motility through the vagus nerve and acts on afferent neurons. PMID- 8444379 TI - [Effects of KW-3635 on the diuretic action of furosemide in rats]. AB - The effects of KW-3635 (sodium (E)-11-[2-(5,6-dimethyl-1-benzimidazolyl) ethylidene]-6,11-dihydrodibenz-[b,e]oxepine-2-carboxylate monohydrate, CAS 127166 41-0), a novel thromboxane A2 (TxA2) receptor antagonist, on furosemide diuresis were examined in rats. After an overnight fast, the rats received either saline or drugs, and 6-hr urine samples were collected. Urine volume, urinary excretion of electrolytes and urine TxB2 were measured. The administration of KW-3635 (10, 30 mg/kg, p.o.) or BM-13505 (10, 30 mg/kg) significantly increased the diuretic effect of furosemide (10 mg/kg, p.o.). Neither drug had any effect on urinary excretion of TxB2. These results demonstrated that the diuretic effect of furosemide was potentiated by TxA2 receptor blockade with KW-3635 or BM-13505. It is suggested that the diuretic effect of furosemide might be modulated by renal production of TxA2 elicited by this drug. PMID- 8444380 TI - [Combined effect of glucocorticoid and TJ-114 (Tsumura Sairei-to)]. AB - TJ-114 (Tsumura Sairei-to) is a powdered extract made from 12 Chinese herbal drugs. TJ-114 is used against various nephrotic diseases and used as an inhibitory treatment for the side effects of glucocorticoids. We expected that TJ 114 would increase the survival ratio of rats given a high dose of glucocorticoid. Therefore, in this study, we investigated the combined effects of glucocorticoid and TJ-114 in rats. An ointment containing fluocinolone acetonide (FA) was applied on the back of 7-week-old Wistar male rats for various periods. TJ-114 was administered orally at the doses of 0.5, 1.0 or 2.0 g/kg simultaneously. The combination with TJ-114 suppressed the loss of body weight by FA. The survival ratio of the FA group was 50%, but it was 83% for the group treated with FA in combination with 0.5 g/kg TJ-114 and no deaths were observed in the other drug combined group. With a lower dose of FA, we investigated its hematological effects and determined the white blood cell (WBC) count. Although the lymphocytes were decreased by FA, the combination with TJ-114 depressed this decrease of lymphocytes significantly. Furthermore, TJ-114 significantly suppressed the insulin increase elicited by FA. Macroscopic observations showed atrophy and decreases in the weights of the thymus, spleen and adrenal, all being target organs of glucocorticoid. The combination with TJ-114 decreased these effects of FA. Moreover, microscopic examinations revealed that FA induced the degeneration of lymphocytes and lymphocyte depletion in the cortex of the thymus, caused atrophy of the white pulp, decreased the extramedullary hematopoiesis of the spleen, and caused the atrophy of zona fasciculata in the adrenal cortex. The combination with TJ-114 depressed these effects significantly. These results suggest that TJ-114 suppresses the adverse side effects of gucocorticoids. PMID- 8444381 TI - [Effects of local anesthetics on rat macrophage phagocytosis]. AB - We examined whether phagocytosis by macrophages (M phi s) is affected by local anesthetics (lidocaine HCl, prilocaine HCl, mepivacaine HCl, tetracaine HCl and procaine HCl). Opsonized zymosan, fetal bovine serum and one local anesthetic were added to each M phi sample. After a 30-min incubation, M phi s were washed to make Giemsa stained slides for counting. The phagocytosis rate was calculated by counting the phagocytosizing M phi s per 200 cells with an optical microscope, and rates for the samples containing local anesthetics were compared with those for the non-treated samples. Inhibition of phagocytosis was reversible, dose dependent and pH dependent for all local anesthetics. Tetracaine HCl inhibited phagocytosis most and procaine HCl, least. These results suggest that local anesthetics at the level of clinical use inhibit leukocyte phagocytosis and therefore may interfere with the normal function of cells fundamental to host defense. PMID- 8444382 TI - Subchronic and chronic studies of the effects of oral administration of acrylic acid to rats. AB - In a 3-month study, groups of 10 male and 10 female Wistar rats were dosed by gavage, 5 times per week, with acrylic acid at doses of 150 or 375 mg/kg body weight. Five male and five female rats in the low-dose group died and six males and nine females given 375 mg/kg died. Pathological examination revealed a dose dependent pronounced irritation in the forestomach and glandular stomach with ulcerations and purulent rhinitides and tubular necroses. Therefore, in comparison with drinking water administration using approximately equivalent doses (2000 or 5000 ppm; see below), administration by gavage was determined not to be suitable for long-term studies using as high as possible doses. In a 12 month study, Wistar rats (20 rats/group/sex) were given drinking water containing 120, 800, 2000 or 5000 ppm acrylic acid (providing doses of about 9, 61, 140 and 331 mg/kg body weight/day, respectively). Satellite groups (10 rats/group/sex) were treated concurrently for 3 months. Acrylic acid at 5000 ppm, and temporarily also at 2000 ppm, led to reduced drinking water consumption in male rats and, to a slight extent, also in female rats. In the males, feed consumption was reduced at 5000 ppm and body weight gain was retarded at 5000 ppm and marginally also at 2000 ppm. These findings indicate palatability problems and their consequences. There were no indications of systemic toxicity and/or any carcinogenic potential. In a carcinogenicity study, Wistar rats (50/group/sex) were given acrylic acid in the drinking water at concentrations of 0, 120, 400 or 1200 ppm (8, 27 or 78 mg/kg body weight/day, respectively) over 26 (males) or 28 (females) months. The concentrations were chosen on the basis of the interim results from the 12-month drinking water study, which had started earlier, and taking into account the longer study duration and geriatric effects to be expected. This carcinogenicity study did not reveal any toxic changes or indications of a carcinogenic potential of acrylic acid with the exception of slightly reduced (statistically not significant) consumption of drinking water. PMID- 8444383 TI - Plasma levels of aluminium after tea ingestion in healthy volunteers. AB - 12 healthy volunteers on a controlled aluminium (Al) diet each consumed a tea infusion (500 ml/70 kg body weight), with either milk or lemon juice as additives, or mineral water, following a three-way crossover design. The concentrations of Al were determined in the diet, mineral water and tea infusions, and in plasma samples collected before and up to 24 hr after consumption of tea or water, using graphite-furnace atomic absorption spectrophotometry or inductively coupled plasma emission spectrometry. Consumption of up to 1.60 mg Al from tea with milk or lemon juice did not increase plasma Al levels compared with consumption of approximately 0.001 mg Al from mineral water. The results suggest that, in the short-term, drinking tea does not contribute significantly to the total body burden of Al. PMID- 8444384 TI - Effects of hickory smoke condensate on gastric carcinogenesis in Wistar rats after treatment with N-methyl-N'-nitro-N-nitrosoguanidine and sodium chloride. AB - Short-term assays in vivo have suggested that hickory smoke condensate (HSC), a food flavouring, might have tumour-initiating and/or promoting activities in the glandular stomach of the rat. In the present study, the modifying effects of HSC on glandular stomach carcinogenesis after initiation with N-methyl-N'-nitro-N nitrosoguanidine (MNNG) and sodium chloride (MNNG salt) were investigated in male Wistar rats. Animals were given MNNG solution (100 ppm) as drinking water and simultaneously fed the diet supplemented with 5% sodium chloride for 8 wk. Matched negative controls received neither MNNG nor sodium chloride. Rats were then fed a basal diet and given HSC solution (1 or 3%) or tap water for the following 32 wk. During the experimental period, treatment with MNNG salt and administration of HSC both brought about growth retardation although the final body weight of rats was comparable between groups. Only two rats treated with MNNG salt followed by 1% HSC developed adenocarcinoma of the stomach. HSC treatment appeared to increase the number of rats with preneoplastic hyperplasias and/or adenocarcinomas in both the fundic and pyloric mucosa, although not to a statistically significant extent. HSC administration significantly increased malondialdehyde levels in the urine and gastric mucosa, the former in a dose dependent manner. The results suggest that HSC has little, if any, promoting effect on two-stage glandular stomach carcinogenesis in rats when given during the post-initiation phase. However, the tumour co-initiating effects of HSC require further clarification. PMID- 8444385 TI - Study on embryo-foetotoxicity of beta-myrcene in the rat. AB - beta-Myrcene is a constituent of many essential oils that have been used extensively in cosmetic fragrances and as flavouring additives in the food industry. Recently, this monoterpene was reported to be an analgesic substance. Notwithstanding the widespread use of myrcene and essential oils containing myrcene in perfume and in food additives, experimental studies on the toxicity of this substance are still scarce. This study aimed to provide data on the embryo foetotoxic potential of beta-myrcene in the rat. beta-Myrcene (0.25, 0.5 and 1.2 g/kg) in corn oil was given orally to Wistar rats from day 6 to 15 of pregnancy. Caesarean sections were performed on day 20 of pregnancy, and the number of resorptions and implantation sites were recorded. Foetuses were weighed, examined for external malformations, and fixed for visceral examination, or cleared and stained with Alizarin Red S for skeleton evaluation. No adverse effects were seen with the two lowest doses tested. Decreased weight gain during the first days of treatment and the death of one of 29 treated dams indicated that the highest dose tested (1.2 g/kg) induced maternal toxicity. A higher incidence of signs of retardation and of anomalies in the foetal skeleton indicated that 1.2 g/kg was also toxic to the rat embryo. From the data presented in this paper the no observed-adverse-effect level for embryo-foetotoxicity could be set at 0.5 g beta myrcene/kg body weight. PMID- 8444386 TI - Rates of utilization of intravenous oleylanilide administered chronically to the rat. AB - The constant injection of [14C]oleylanilide into the vena cava of Wistar rats for 7 days with osmotic minipumps was used to estimate tissue distribution of chronically administered anilides. The largest concentrations of the anilide were found in the brown adipose tissue; all other tissues showed much lower proportions. When anilide distribution was expressed as nmol/g lipid, the high concentration of the compound in the brown adipose tissue contrasted with its very low presence in the white adipose tissue; all other tissues showed intermediate concentrations. Anilide-treated rats consumed more food and lost more weight than did controls; their energy balance showed higher energy inefficiency. The results suggest a possible effect of anilides on the thermogenic pathway of the rat brown adipose tissue. In addition, there was a large individual variability in the proportions of anilide present in all tissues, from as little as 0.3% of the total anilide injected in some animals to 6% in others. PMID- 8444387 TI - Nitrosation of the antimicrobial drug hexetidine: nitrosamines derived from a triamine decomposition product. AB - Five new nitrosamines were identified as nitrosation products of N1,N3-bis(2 ethylhexyl)-2-methyl-1,2,3-propantriamine, a hydrolysis product usually found in preparations of the antimicrobial drug hexetidine. All nitrosamines are formed after deamination of the primary amino group by nitrosation of one of the two secondary amino groups. The propantriamine derivative is very easily nitrosatable, with total nitrosamine yields in the upper range of a comparative scale of drug nitrosatability. PMID- 8444388 TI - Effects of protein deficiency on lipid peroxidation in the small intestine and liver of rats. AB - This study investigated the influence of protein restriction on lipid peroxide content (thiobarbituric acid-reactive substances) and the intracellular antioxidant defence system in the small intestine and the liver. Weanling male Sprague-Dawley rats were divided into two groups: a low-protein group fed ad lib. a diet containing 6% casein for 4 wk, and a control group fed a diet containing 22% casein but restricted to the same dietary intake as that of the low-protein group. Compared with pair-fed controls, the protein-deficient rats exhibited a decrease in glutathione content in the small intestine and the liver. Thiobarbituric acid-reactive substances were increased in the intestine only. Data on the enzymatic antioxidant defence system in the protein-deficient animals showed an increase in catalase activity in the intestine but a decrease of this activity in the liver. The activity of selenium-dependent glutathione peroxidase was decreased in the liver and remained unchanged in the intestine. Superoxide dismutase was not modified by protein deficiency in either tissue. In control rats, enzyme activities were 6-43 times higher in the liver than in the intestine. The deleterious effects of protein deficiency appeared more marked in the intestine. PMID- 8444389 TI - Results with OECD recommended positive control sensitizers in the maximization, Buehler and local lymph node assays. AB - The guinea pig maximization test and the Buehler occluded patch test are used widely to identify the sensitization potential of new chemicals. This information enables toxicologists and/or regulatory authorities to determine whether a chemical should be classified formally as a skin sensitizer. Both to improve and to harmonize these assessments internationally, the OECD has recommended recently that moderate rather than strong contact sensitizers are used as positive control substances. The purpose is to ensure an adequate level of sensitivity in sensitization assays performed at specific testing establishments. Results from two laboratories reported here show that the minimum acceptable standard laid down by the OECD can be achieved and indeed commonly exceeded by a substantial margin. Furthermore, results with these positive controls in a new method, the local lymph node assay, also appear to satisfy similar criteria, suggesting results from this assay, including negative data, should be acceptable for classification purposes. However, a review of the way in which results with new chemicals will be interpreted for regulatory purposes, in the context of positive control data, reveals that considerable inadequacies still exist. It is recommended that ultimately, sensitization data can only be interpreted meaningfully (i.e. to protect humans from sensitization hazards) by considering the potency of the contact allergen in the context of the sensitivity of the assay performed at the particular testing institution. PMID- 8444390 TI - Justification of the enucleated eye test with eyes of slaughterhouse animals as an alternative to the Draize eye irritation test with rabbits. AB - The enucleated eye test (EET) with the isolated eye of rabbits has been recognized as a valuable alternative to the Draize test, because it represents a test system nearest to the in vivo test, without the need to use live animals. In this ex vivo bioassay, three parameters are measured to detect possible adverse eye effects, namely corneal swelling, corneal opacity and fluorescein retention. The measurement of corneal swelling in this assay guarantees a highly objective and discriminative parameter. In combination with the detailed observation of corneal opacity and fluorescein retention, a reliable evaluation of the eye irritation potential of test materials is achieved. However, laboratory animals are still necessary as eye donors. The use of slaughter animals, such as the cow, the pig and the chicken, as possible as eye donors for the EET was therefore examined. From these candidates, the chicken appeared to be the most practicable. 21 reference compounds, ranging from non-irritant to severe irritant, which had been tested previously in a validation study on alternative test methods for eye irritation testing, sponsored by the Commission of the European Communities, were examined in the Chicken Enucleated Eye Test (CEET). When compared with the in vivo EC classification, the CEET correctly classified each of the compounds that must be labelled in the EC as irritant (R36) or severely irritant (R41). In addition, since the CEET recognizes three levels of irritancy rather than two (as in the case of the EC classification) a small number of the compounds were recognized as slightly irritant, which according to the EC classification need not be labelled. It was concluded that this ex vivo test system is highly accurate in the assessment of eye irritation potential without the use of laboratory animals. PMID- 8444391 TI - [Tuberculous spondylitis as a "rare cause" of backache. Early diagnosis for prevention of gibbus, scoliosis and paralysis]. AB - It appears that tuberculous spondylitis is becoming more common again-also in Germany. In the present case report, the clinical picture, diagnosis and treatment of this condition are discussed. Clinical findings, in combination with radiological examinations, CT and MRI enable an early diagnosis to be established. This is of decisive importance if extensive destruction and axial deformities of the spine with resulting pareses are to be prevented. PMID- 8444392 TI - [Peculiarities of drug therapy in the elderly]. AB - OBJECTIVES: Old people (over 70) are often treated with drugs. With respect to the indications for drug treatment, pharmacokinetics and pharmacodynamics, as well as undesired adverse drug reactions, there are a number of points peculiar to old age. MAJOR INFORMATION: The usefulness of so-called geriatric drugs in the treatment of age-associated disorders continues to be controversial. The proportionate reduction in fat-free body mass leads to a change in drug distribution volumes, which can have an influence on the half-life of the substances concerned. While the perfusion of the liver and kidneys diminishes, effects on drug metabolism tend to be due to disease rather than aging processes. In old age, the incidence of side effects of medication is increased-the main cause of this, however, being the greater number of medicaments taken simultaneously, and not age in itself. A generally passive attitude towards treatment of the old patient is, however, not justified. CONCLUSIONS: In old age, too, the general rule applies: as few drugs as possible, but then used selectively. Therapeutic regimens should be regularly checked and the results of treatment critically evaluated; a specific search should be made for adverse reactions. PMID- 8444393 TI - [Surgical therapy of frequent hand injuries. Part 2: Injuries of the tendons, neurovascular bundles and soft tissues]. AB - Injuries to the extensor and flexor tendons are among the most common injuries to the hand (cf. Part 1 of this overview). Severance of individual flexor tendons as also isolated injuries to individual nerves may occasionally be overlooked. In the case of doubt, operative revision is to be recommended. With the aid of dynamic fixation as described by Kleinert, good functional results can be achieved even with injuries "in no-man's-land". In the event of infections following minor injuries, conservative treatment should be applied only in the early stage; thereafter, surgical revision is indicated. In the region of the flexor tendons, immediate surgery is necessary. Also in the case of a paronychia or a panaritium, early surgical treatment of the abscess and necroses is advisable. PMID- 8444394 TI - [Diagnosis in general practice. Part 3. Vertigo]. PMID- 8444395 TI - [Single dose therapy of uncomplicated urinary tract infections in women. Remission rates with ciprofloxacin in two prospective randomized comparative studies]. AB - In a prospective randomized study, the clinical effectiveness of ciprofloxacin at a single dose of 250 mg p.o. was compared with that of two oral doses of 250 mg bid administered for two days in women with urinary tract infection following gynecological procedures. A healing rate of 95% was achieved with both single dose (n = 62) and two-day treatment (n = 65). In a further prospective randomized multicenter study, single-dose therapy with 250 mg of oral ciprofloxacin in women with uncomplicated urinary tract infection was compared with three days of ambulatory treatment with 2 x 250 mg/day. In the case of these patients, the diagnosis was made and treatment applied in the doctor's office by one of seven specialist gynecologists practicing in the city area of Essen. The healing rate of 78% (n = 46) achieved with single-dose treatment was significantly inferior to the 91% seen with the three-day regimen (n = 53, p < 0.05). PMID- 8444396 TI - [The computer as a vigilant obstetric monitor. A new kind of CTG analysis program should help prevent early infantile brain damage]. PMID- 8444397 TI - [Management of lipid disorders in general practice. Dr. H. G. Horstmann, Essen family physician, takes a stand. Interview by Maite Citoler]. PMID- 8444398 TI - [Mother earth heals. Self medication already in chimpanzee]. PMID- 8444399 TI - Classification of adrenergic receptors: functional approaches. PMID- 8444400 TI - [Cholecystolithiasis and choledocholithiasis cured by methyl tert butyl ether (MTBE) combined with EST]. AB - A 70-year old male patient was admitted to hospital with fever and right upper quadrant pain. Ultrasonography and cholecystography revealed acute cholecystitis associated with multiple stones not only in the gallbladder but also in the common bile duct. Percutaneous trans-gallbladder drainage (PTGBD) was performed because of his persisting complaints and severe inflammatory change of the gallbladder. Operation was not considered due to his cardiac problem, so we tried direct dissolution treatment of the gallstones by using Methyl tert butyl ether (MTBE) through the percutaneous transhepatic catheter. Following maximal aspiration of the gallbladder contents, same amount of MTBE was infused into and the patient was kept in the right-side-down position for an hour. After 30 times of MTBE treatment, all stones in the gallbladder were thoroughly dissolved without any side effect. A residual stone in the common bile duct was easily taken out by endoscopic sphincterotomy. PMID- 8444401 TI - [Arteriosclerosis obliterans that was improved by LDL apheresis]. AB - We reported here a case of arteriosclerosis obliterans (ASO) in which clinical symptoms and signs were improved after repeated LDL apheresis. The patient was a 70-year-old man who was diagnosed as having ASO in 1989. Although drug treatment started for the arterial disease, such clinical manifestations as rubor and intermittent claudication were gradually worsening. In 1991, the patient was also found to have diabetes mellitus (DM), leading to admission for its treatment. Insulin therapy was initially required, but it finally became possible to maintain a good control of DM with diet therapy alone. Since hypercholesterolemia (402 mg/dl) was noted on admission, we began to give the patient pravastatin. In response to the medication, serum total cholesterol (TC) levels declined to 270 mg/dl, but no further improvement was obtained. We therefore decided to perform LDL apheresis on the patient, hoping the improvement of both ASO and hypercholesterolemia. After six series of LDL apheresis were performed during 4 weeks, ASO-related signs and symptoms (i. e., intermittent claudication) were remarkably improved, and serum TC levels were decreased below 200 mg/dl. Our experience in the present case suggested that this procedure would be useful as an effective choice of treatment for ASO, but further studies as to the indication and protocol of this therapeutic maneuver will be clearly needed. PMID- 8444402 TI - [Ventilatory mechanical analysis of respiratory depression induced by serotonin]. AB - This study was aimed to prove the pharmacological characteristics of 5 hydroxytryptamine (5-HT)-induced respiratory depression, especially apnea. Effects of 5-HT-receptor agonists and antagonists on respiratory parameters were examined using anesthetized and spontaneously breathing rats. A bolus intravenous administration of 5-HT (3.125-25 micrograms/kg) immediately produced an apnea, the duration of which increased in a dose-related manner. This response was antagonized by a selective 5-HT3-receptor antagonist, GR38032F (10 and 100 micrograms/kg). Ketanserin, a 5-HT2-receptor antagonist, 100 micrograms/kg also inhibited the 5-HT-induced apnea. In addition, the effect of 5-HT-induced apnea mimicked by 2-methyl-5-HT (3.125-50 micrograms/kg), a 5-HT3-receptor agonist, and by alpha-methyl-5-HT (3.125-25 micrograms/kg), a 5-HT2-receptor agonist. On the other hand, 5-HT produced a decrease in lung compliance and an increase in lung resistance in a dose-related manner. The 5-HT-induced changes in lung compliance and lung resistance were antagonized by ketanserin (100 micrograms/kg), but not by GR38032F (100 micrograms/kg). Furthermore, alpha-methyl-5-HT caused bronchoconstriction as did 5-HT, but 2-methyl-5-HT did not. Although bilateral vagotomy at the supra-nodose ganglia completely prevented 5-HT-induced apnea, cervical vagotomy below the superior laryngeal nerve did not prevent this change. On the other hand, cervical vagotomy almost prevented bronchoconstrictive responses, and completely blocked alpha-methyl-5-HT-induced apnea. These results suggest that 5-HT-induced apnea might be mediated through 5-HT3-receptor mechanisms of the vagal afferent system including the nodose ganglia, and that 5 HT2-receptor mechanisms also contribute to the apnea via the afferent cervical vagus nerves. Direct and indirect bronchoconstriction might also be partly involved in 5-HT-induced apnea. PMID- 8444404 TI - [Identification and characterization of hydrophobic ligand binding region in glutathione S-transferase P]. AB - Recombinant glutathione S-transferase P (GST-P) was purified in a homogeneous state. Fatty acid analysis by gas-liquid chromatography-mass spectrometry (GC-MS) revealed that GST-P forms 1:1 complex with fatty acids, mostly palmitic acid or stearic acid, which were hardly isolated from the complex even through Lipidex 1,000 column chromatography at 37 degrees C. Temperature dependent analysis of 1H NMR on the association between GST-P and fatty acids indicated that molecular motion of fatty acids were strongly restrained in a hydrophobic 'pocket' below the temperature of protein denaturation. On the other hand, there existed another hydrophobic ligand binding region, to which fatty acid and bilirubin would bind with relatively lower affinity. The binding region was determined to be at around 142-157 residues from amino terminus by the studies of GST-P binding to fatty acid-linked Sepharose and affinity labelings with either fluorescent fatty acid or bilirubin. The binding to this region noncompetitively inhibited the enzyme activity. Furthermore, circular dichroism (CD) analysis showed that the binding of hydrophobic ligands changed the secondary structure of GST-P, which suggested that the enzyme activity was regulated through conformational changes. As tryptophan 38 was assumed to locate at the active center from the study of site directed mutagenesis, conformation of the active center was investigated by measuring the intrinsic tryptophan fluorescence. It showed that hydrophobic ligand binding caused the drastic conformational change, of which would be referred to the regulation of the enzyme activity. PMID- 8444403 TI - [Presence and localization of proteins immunologically related to membrane skeletal proteins in human skin]. AB - Recent biochemical studies have shown that spectrin, protein 4.1, and actin form a skeletal protein network that underlines the inner surface of the erythrocyte membrane. The skeleton is a flexible structure that appears to be important in maintaining the shape and mechanical properties of the erythrocyte. Recent studies indicate that immunoanalogues of erythrocyte membrane skeletal proteins and ankyrin (protein 2.1) have been found in a wide variety of non-erythroid tissues. In the present study, in order to examine if human skin contains membrane skeletal proteins, immunochemical analysis was utilized using antibodies against anti-spectrin, anti-beta-fodrin (non-erythroid spectrin), anti-protein 4.1 and anti-ankyrin antibodies. Immunoblot analysis of human epidermis with anti spectrin and anti-beta-fodrin antibodies revealed that human epidermis contains 240 kDa and 235 kDa spectrin-like proteins, which might be identical to brain fodrin. Human epidermis also contains 4.1-like proteins of 80 kDa and 78 kDa that cross react with anti-protein 4.1 antibodies, and contains ankyrin-like proteins of 210 kDa that cross react with anti-ankyrin antibodies. Analysis with immunofluorescence microscopy revealed that these antibodies reacted along the plasma membranes of human epidermal keratinocytes, eccrine sweat gland cells and sweat ductal cells. These results suggest that a membrane skeletal protein lattice might exist in these cells. Cultured human epidermal keratinocyte in the low Ca2+ medium (0.15 mM) showed that immunoreactive form of protein 4.1 and actin were present diffusely in the cytoplasm. When the cells were cultured with standardized Ca2+ medium (1.85 mM), protein 4.1 and actin were observed linearly along the cell margin and in the cytoplasm. Similar patterns of distribution were observed when anti-beta-fodrin antibody was used. Movement of membrane skeletal proteins from cytosol to the membrane suggest that these proteins or membrane skeletal lattice might play an important role in the formation of intercellular junctions. PMID- 8444405 TI - [Experimental study of the effectiveness of ECMO (extracorporeal membrane oxygenation) and PGI2 derivative against severe respiratory failure]. AB - Severe respiratory failure was made on twenty dogs with intratracheal administration of the linoleic acid to study the effectiveness of ECMO. The dogs were divided into four groups: First group (GI); respiratory failure, second group (G II); respiratory failure with pumpless A-V bypass, third group (G III); respiratory failure with V-A bypass, fourth group (G IV); respiratory failure with V-A bypass and administration of OP-41483 (PGI2 derivative). The effectiveness of ECMO was studied with different concentration of Prostaglandin I2 (PGI2) and Thromboxane A2 (TxA2). This experiment showed significant prolongation of mean survival time in dogs of respiratory failure treated with the use of ECMO. In GI and G II, TxB2, metabolic product of TxA2, increased and the ratio of 6-ketoPGF1 alpha, metabolic product of PGI2, versus TxB2, decreased progressively. In G III and G IV, the TxB2 was increased during the first two or three hours after intratracheal administration of linoleic acid and then reached a steady level. In G3, the ratio of 6-ketoPGF1 alpha versus TxB2 was approximately 0.5 after the linoleic acid administration. However, in the case of G IV with combined application of PGI2 derivative, the ratio decreased to 0.59 +/ 0.08 in one or two hours after the administration, then increased progressively and reached a value of 1.04 +/- 0.27 in eight hours after the linoleic acid administration. In conclusion, this study demonstrates that therapeutical effects of ECMO against respiratory failure could be elevated by using PGI2 derivative. PMID- 8444406 TI - Acute transverse myelopathy in multiple sclerosis: clinical and laboratory analyses. AB - Seventy-three consecutive patients with clinically definite multiple sclerosis (MS) were classified into 2 subgroups: group A, consisting of 21 patients who had shown acute transverse myelopathy (ATM) during the course of illness; and group B, 52 patients without ATM. The clinical features of these 2 groups were analysed prospectively, and MRI findings, trimodal evoked potentials (EPs), CSF analyses and HLA profiles were compared between 2 groups, and some significant differences were found. Clinical analyses showed later onset, less frequent occurrence of brainstem, cerebellar and cerebral symptoms, and more frequent and severe involvements of the optic nerve in group A compared with group B, and the clinical features of group B were quite similar to those of previous western series. On MRI findings, the degree of cerebral white matter and periventricular lesions were higher in group B, the moderate, large, ovoid or confluent lesions were lower in number in group A, and brainstem lesions were less common in group A. The number of the patients with abnormal findings on brainstem auditory EPs (BAEPs) were smaller in group A. HLA-DRw8 was significantly increased and DR9 was significantly decreased in group B compared with controls. HLA-DQw7 and DR4 were raised in group A and group B, respectively, and the frequency of DQW7 and DR4 were different between these 2 groups. The patients in group A may be different clinically, genetically and possibly pathologically from those in group B, and seem to constitute a distinct subgroup in patients with MS. PMID- 8444407 TI - [Overgrowth and DNA synthesis of neuroepithelium in embryonic stages of induced Long-Evans rat myeloschisis]. AB - Overgrowth of the myeloschisis, namely the excessive amount of the neural plate tissue, has been reported in the human myeloschisis. However, it is still debatable how the overgrowth develops and whether the overgrowth is the cause, or the secondary effect of spinal dysraphism. The author induced myeloschisis in the fetuses of Long-Evans rats by the administration of ethylenethiourea (ETU) to pregnant rats on day 10 of gestation. The fetuses were removed 1 hour after the treatment with bromodeoxyuridine (BrdU) to the dams on day 14 and 21. The fetuses were fixed in alcohol and embedded in paraffin. H-E staining and the immunohistologic examination were performed on the staining patterns to anti neurofilament (NFP), anti-glial fibrillary acidic protein (GFAP) and anti-BrdU antibody by ABC method. On day 14, the lateral portion of everted neural plate showed a loose arrangement of cells and there was rosette formation in the mesoderm. On day 21, cell necrosis was observed at the dorsolateral portion of myeloschisis, although the ventral portion showed almost normal cytoarchitecture and was positive to NFP and GFAP. The cause of myeloschisis in this model is supposed to be the local and direct cytotoxic effect of ETU to neuro-ectodermal junction. On day 14, control animals contained few BrdU-incorporated cells at the basal plate of neural tube. In contrast, everted neural plate showed an active uptake of BrdU diffusely in the subependymal matrix layer cells. Overgrowth was not yet identified. On day 21, overgrowth of myeloschisis was found in spite of a few positive cells to BrdU which was identical to the control animals. These findings seem to suggest that cells in the myeloschisis retain their ability of DNA synthesis for longer periods of development and overgrowth found on day 21 is possibly a secondary effect of spinal dysraphism in this model. PMID- 8444408 TI - [Effects of medium chain triglyceride administration on liver regeneration after partial hepatectomy in rats]. AB - The influence of lipid emulsion, especially medium chain triglyceride (MCT), on liver regeneration was investigated after 70% hepatectomy in rats. The rats received one of the following 3 solutions as a fuel source in total parenteral nutrition (TPN) regimen: a glucose solution (Group-G), a mixture of long chain triglyceride (LCT) and glucose (Group-L), or a mixture of MCT and glucose (Group M). The calorie ratio of fat to glucose in LCT and MCT was 1 to 1. The energy charge (EC) of the regenerating liver decreased at 6 or 12 hours after hepatectomy and returned to the pre-operative level at 24 hours in each group. But EC at 6 hours was significantly higher in group-M than in group-G. Lipoperoxide (LPO) in regenerating liver was significantly lower in group-Mand-L than in group-G at 12 hours after hepatectomy, but it was significantly higher in group-M than in group-G and -L at 48 hours. Labeling index (LI) of bromodeoxyuridine (BrdU) was significantly higher in group-Mand L than in group-G at 24 hours after hepatectomy. These results indicate that MCT may be beneficial energy substrates in acute phase of regenerating liver. Although lipid emulsion has beneficial effect on the liver regeneration after hepatectomy, in recovery phase of liver regeneration, addition of LCT with MCT may be considered more beneficial. PMID- 8444409 TI - Hemodynamic and humoral changes after liver transplantation in patients with cirrhosis. AB - Splanchnic and systemic hemodynamics and plasma levels of aldosterone, glucagon and plasma renin were investigated in 12 patients with advanced cirrhosis before and 2 wk (14.6 +/- 2.8 days) and 2 mo (60.8 +/- 10.5 days) after orthotopic liver transplantation. Liver transplant was followed by significant (p < 0.01) changes in systemic hemodynamics at 2 wk, with a marked reduction in cardiac index (4.9 +/- 0.8 vs. 3.7 +/- 0.7 L/min.m2) and increases in mean arterial pressure (79 +/- 8 vs. 101 +/- 11 mm Hg) and peripheral vascular resistance (721 +/- 149 vs. 1,274 +/- 253 dyn.sec.cm-5). Two months after liver transplant, we saw further significant increases in peripheral vascular resistance (1,700 +/- 341 dyn.sec.cm 5; p < 0.05) without changes in cardiac index. Hepatic venous pressure gradient, very high before transplantation, was normal 2 wk after liver transplant (18.7 +/ 3.0 vs. 2.1 +/- 0.8 mm Hg; p < 0.01). Hepatic blood flow rose markedly from 1.03 +/- 0.46 to 2.25 +/- 0.79 L/min (p < 0.01) and was still elevated at 2 mo (1.84 +/- 0.74 L/min). Azygos blood flow had not changed after 2 wk with respect to pretransplant values (0.65 +/- 0.26 vs. 0.69 +/- 0.39 L/min) but had decreased significantly at 2 mo (0.39 +/- 0.16 L/min; p < 0.05). The elevated aldosterone, plasma renin and glucagon levels found in our cirrhotic patients before transplantation decreased to near-normal values 2 wk after the procedure. These results suggest that most of the hemodynamic and humoral abnormalities characteristic of advanced cirrhosis are reversed after liver transplant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444410 TI - The intraportal lymphoid nodule and its environment in chronic active hepatitis C: an immunohistochemical study. AB - Intraportal lymphoid nodules have been observed in liver biopsy specimens from patients with autoimmune liver disease and chronic active hepatitis C. They are characterized by a nodular lymphocyte aggregate with a germinal center. The purpose of this in situ immunophenotyping study was to determine immunohistochemically the phenotype of immunocompetent cells in and around intraportal lymphoid nodules in patients with chronic hepatitis C. For comparison, we also examined lymphoid nodules in patients with autoimmune liver disease. Liver biopsy specimens from 13 unselected patients with CAH and hepatitis C antibodies and from 7 unselected patients with autoimmune liver disease seen during the same period were studied. Sections of snap-frozen specimens were immunostained with monoclonal antibodies directed against different subsets of T cells, B cells, follicular dendritic cells and macrophages. Intraportal lymphoid nodules were observed in 11 of 13 patients with chronic hepatitis C. They appeared as lymphoid follicles with activated B cells in germinal centers surrounded by a follicular dendritic cell network. A mantle zone of B cells was present around the aggregate of activated B cells. A T-cell zone comprising CD4-positive helper T cells, CD8-positive suppressor/cytotoxic T cells and a few CD25-positive activated T cells expressing interleukin-2 receptor was seen at the periphery of the nodules. Human leukocyte antigen DR was expressed by B cells and by T cells, indicating that T cells were activated. The immunocompetent cells observed in piecemeal necrosis were predominantly CD4 helper T cells, whereas those seen in the lobule were predominantly CD8 suppressor/cytotoxic T cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444411 TI - Interferon-alpha and zidovudine combination therapy for chronic hepatitis B: results of a randomized, placebo-controlled trial. AB - Interferon-alpha therapy leads to HBeAg seroconversion in only one third of patients with chronic hepatitis B. In an attempt to increase the seroconversion rate, we investigated the combination of interferon-alpha and zidovudine in a subset of patients with presumably low response rates for interferon-alpha monotherapy. In a double-blind, controlled trial, 24 HBeAg-positive patients were randomized to receive lymphoblastoid interferon-alpha in subcutaneous doses increasing to 5 MU daily, combined with zidovudine given orally in doses increasing from 500 to 1,000 mg/day or with placebo for 16 wk. Treatment effects were monitored by quantitative assessment of HBV DNA, HBeAg and HBV DNA polymerase. Six months after termination of therapy, 1 of 12 (8%; 95% confidence interval = 2% to 39%) patients treated with interferon-alpha plus zidovudine and 2 of 12 (17%; 95% confidence interval 2% to 48%) patients from the control group exhibited responses (HBeAg seroconversion). All patients remained HBsAg positive. The only responder of the interferon-alpha-zidovudine group relapsed after cessation of therapy, so none of the zidovudine-treated patients were HBeAg negative at the end of follow-up. No significant difference in AST level or in any of the virological markers was observed between the two groups during the course of the study. Adverse effects (anemia, leukopenia) necessitated reduction in the dose of zidovudine in 50% and of interferon-alpha in 42% of the patients treated with interferon-alpha plus zidovudine; in the control group these rates were 0% for placebo and 8% for interferon-alpha. In conclusion, the antiviral effect of interferon-alpha in chronic hepatitis B was not enhanced by additional zidovudine treatment. The combination therapy induced considerable side effects leading to dose reduction for both zidovudine and interferon-alpha. For combination therapy with interferon-alpha, oral nucleoside analogs with more potent antiviral effects and less toxicity than zidovudine should be developed. PMID- 8444412 TI - Formation of 7 alpha- and 7 beta-hydroxylated bile acid precursors from 27 hydroxycholesterol in human liver microsomes and mitochondria. AB - In a search for enzymes involved in the formation of bile acids from 27 hydroxycholesterol in humans, the metabolism of this and other side-chain oxygenated steroids was studied in human liver microsomes and mitochondria. The microsomal fraction contained enzyme(s) catalyzing 7 alpha-hydroxylation of 27 hydroxycholesterol and 3 beta-hydroxy-5-cholestenoic acid, whereas the 7 alpha hydroxylation of cholesterol and 3 beta-hydroxy-5-cholenoic acid was low. Only small amounts of 7 beta-hydroxylated products were formed. Purification and subfractionation of microsomal protein yielded a fraction of cytochrome P-450, which required NADPH and NADPH-cytochrome P-450 reductase and catalyzed 7 alpha hydroxylation of the side-chain oxygenated 3 beta-hydroxy-delta 5-C27-steroids but was inactive toward cholesterol. Added cholesterol did not inhibit the observed enzymatic activity. The results provide evidence that this enzyme is different from cholesterol 7 alpha-hydroxylase. The mitochondrial fraction contained enzyme(s) that catalyzed an isocitrate-dependent 7 alpha-hydroxylation of 3 beta-hydroxy-5-cholestenoic acid. The activity was much lower with 27 hydroxycholesterol. The mitochondrial fraction also catalyzed the oxidation of the 27-hydroxy group and contained a 3 beta-hydroxy-delta 5-steroid dehydrogenase active on 7 alpha-hydroxylated C27-steroids. The metabolic end product of the reactions catalyzed by these enzymes was 7 alpha-hydroxy-3-oxo-4-cholestenoic acid. A considerable fraction of the 7 alpha-hydroxy-delta 5 intermediates was also converted to the corresponding 7 beta-hydroxysteroids, probably by way of the 7-oxosteroids, suggesting the presence of an epimerizing enzyme in the mitochondrial fraction. PMID- 8444413 TI - Peroxisomes in cirrhosis of the human liver: a cytochemical, ultrastructural and quantitative study. AB - Hepatocellular peroxisomes in 32 patients with cirrhosis were studied by means of catalase cytochemical and morphometric analysis. Seven normal human livers were used as controls. The severity of the cirrhosis was determined with the Child Turcotte criteria. Under the light microscope, a decrease in catalase staining was observed in 12 livers. Staining showed a weak inverse correlation with severity of the cirrhotic process. Peroxisomes revealed a perinuclear configuration in 24 patients. Morphometric analysis of peroxisomes was performed on 14 cirrhotic livers and revealed a near doubling of the number of organelles, with a compensatory decrease in mean peroxisomal diameter: no appreciable change in total volume of the peroxisome compartment was found. Cytoplasmic invaginations, protrusions and gastruloid cisternae were sparse. Apparently, peroxisomal proliferation in liver cells appeared early in the cirrhotic process. In all 10 livers with a perinuclear configuration of the peroxisomes that were processed for electron microscopy, a morphometrically confirmed increase in the number of peroxisomes was observed. Peroxisomes frequently showed transparent matrical spots and angular profiles. In two patients nucleoid-containing peroxisomes were observed. Although variation between individual patients was high, peroxisomal changes were observed in each cirrhotic liver. No relationship between morphological or morphometric alterations in peroxisomal compartment on one side and the severity of the disease or the type of cirrhotic nodules on the other side was observed. PMID- 8444414 TI - Prevalence and characterization of neutrophil cytoplasmic antibodies in autoimmune liver diseases. AB - To evaluate the diagnostic significance of neutrophil cytoplasmic antibodies in chronic liver diseases, we assessed the prevalence of neutrophil cytoplasmic antibodies in autoimmune liver diseases, in particular in primary sclerosing cholangitis, autoimmune chronic active hepatitis and primary biliary cirrhosis, and we also determined the specificity of perinuclear-pattern neutrophil cytoplasmic antibodies for these autoimmune liver diseases by testing sera from patients with nonautoimmune chronic liver diseases. Neutrophil cytoplasmic antibodies were detected in 79% of sera from patients with primary sclerosing cholangitis (n = 24), in 88% of sera from patients with autoimmune chronic active hepatitis (n = 24) and in 28% of sera from patients with primary biliary cirrhosis (n = 25). The presence of neutrophil cytoplasmic antibodies in these diseases correlated significantly (p < 0.008) with the presence of cirrhosis. Neutrophil cytoplasmic antibodies were not detected in nonautoimmune liver diseases. All neutrophil cytoplasmic antibody-positive sera produced a perinuclear fluorescence pattern on ethanol-fixed granulocytes. On neutrophils fixed with paraformaldehyde, a granular cytoplasmic immunofluorescence pattern was observed, demonstrating the cytoplasmic nature of the antigen or antigens involved. Further characterization studies showed that neutrophil cytoplasmic antibodies in autoimmune liver diseases are not directed against myeloperoxidase, proteinase 3 or elastase, the neutrophil cytoplasmic antibody specificities associated with necrotizing vasculitis, glomerulonephritis or both. On Western blots neutrophil cytoplasmic antibodies in autoimmune liver diseases showed reactivity with either lactoferrin, a 67/66-kD protein combination or a 40-kD polypeptide. Reactivity with either of these proteins was observed in sera from patients with primary sclerosing cholangitis (38%), autoimmune chronic active hepatitis (17%) and primary biliary cirrhosis (20%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444415 TI - Mitochondrial dysfunction in alcoholic patients as assessed by breath analysis. AB - Mitochondria of patients with alcoholic liver disease are morphologically abnormal, and mitochondria isolated from animals exposed to ethanol exhibit functional deficiencies in vitro. Because the functional consequences of the morphological alterations and the relevance of in vitro observations to mitochondrial function in alcoholic subjects are not clear, we assessed mitochondrial function noninvasively with a breath test. Mitochondrial function was assessed by measuring the exhalation of 14CO2 after administration of 1 microCi 2-keto[1-14C]isocaproic acid, the decarboxylation of which occurs in mitochondria. The results of the 2-keto[1-14C]isocaproic acid breath test in 17 alcoholic subjects were compared with the results in healthy controls and patients with nonalcoholic liver disease. The peak exhalation of 14CO2 and the fraction of the administered dose decarboxylated in 60 min were significantly lower in alcoholic patients than in healthy controls or patients with nonalcoholic liver disease. In alcoholic patients 2-keto[1-14C]isocaproic acid decarboxylation was impaired in the presence of normal conventional and quantitative liver function as assessed by aminopyrine breath test and galactose elimination capacity, indicating that 2-keto[1-14C]isocaproic acid decarboxylation does not simply reflect decreased functional liver mass. We conclude that mitochondrial function as reflected by 2-keto[1-14C]isocaproic acid decarboxylation is impaired in chronic alcoholic patients. The functional impairment is specific for excessive ethanol consumption and not a reflection of decreased global liver function or the presence of cirrhosis. 2-Keto[1 14C]isocaproic acid decarboxylation could thus be useful as a marker of excessive ethanol consumption. PMID- 8444416 TI - Creatine kinase-BB: a marker of liver sinusoidal damage in ischemia-reperfusion. AB - Cell damage within the sinusoidal lining of human liver grafts during transplantation is an early event that is critical in ischemia-reperfusion injury and probably plays a key role in primary liver dysfunction after transplantation. No simple biochemical marker for sinusoidal injury is currently available. Because creatine kinase activity has been described in heart endothelial cells, we hypothesized that release of this enzyme might serve as an index of sinusoidal injury. To test this hypothesis, we used several in vivo and in vitro experimental models. Occlusion of the rat hepatic pedicle in situ for 60 min (normothermic ischemia) induced a significant increase in serum creatine kinase levels relative to those in laparotomized controls (2,530 +/- 530 vs. 389 +/- 64 IU/L, mean +/- SEM; p < 0.005). In the isolated perfused rat liver, 60-min ischemia induced early (< or = 3 min) creatine kinase and AST release (0.87 +/- 0.14 vs. 0.08 +/- 0.01 IU/min/gm liver, respectively). A similar phenomenon was observed after 24-hr or 48-hr hypothermic conservation in University of Wisconsin solution. Electrophoretic analysis and immunoinhibition studies showed that creatine kinase activity comprised creatine kinase-BB (approximately 50%) and mitochondrial creatine kinase. Trypan blue infusion showed a loss of viability in sinusoidal cells, whereas hepatocytes were relatively spared. Finally, murine sinusoidal cells were isolated, cultured and then lysed by a freeze-thaw cycle and sonication. Creatine kinase activity was found in endothelial cells (creatine kinase-BB), Kupffer cells (creatine kinase-BB) and Ito cells (creatine kinase MM). Creatine kinase-BB was not found in hepatocytes, but mitochondrial creatine kinase was detected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444417 TI - Administration of hepatic stimulatory substance alone or with other liver growth factors does not ameliorate acetaminophen-induced liver failure. AB - Sixty-two beagle dogs were given three doses of acetaminophen over a period of 24 hr in a fulminant liver failure model that is 70% lethal in 72 hr. Treatment of the animals with hepatic stimulatory substance alone or in a mixture with insulin, transforming growth factor-alpha and insulin-like growth factor II had no effect on mortality. Evidence of maximum regeneration with a mitotic index 20 to 25 times resting was the same in treated and untreated animals. Similarly, the biochemical and hematological indexes of liver injury were unaffected by therapy. These studies illustrate the futility of treating fulminant liver failure with exogenous growth factors that apparently are already present in large amounts in the natural response to liver injury. The results suggest that on-going liver injury by mechanisms other than lack of growth factors is the central problem of fulminant liver failure. If so, provision of regeneration-stimulating substance is an inappropriate therapeutic strategy. PMID- 8444418 TI - Accumulation of organic anion in intracellular vesicles of cultured rat hepatocytes is mediated by the canalicular multispecific organic anion transporter. AB - Transport of organic anions within hepatocytes and the possible involvement of intracellular vesicles were studied with fluorescence microscopy. For this purpose monochlorobimane, a nonfluorescent hydrophobic compound that readily permeates into cells and is conjugated with glutathione to form the fluorescent glutathione bimane, was used. In the isolated perfused livers of normal rats, glutathione bimane is rapidly secreted into bile. In contrast, in our study of livers from mutant TR- rats, a 100-fold reduction in glutathione bimane secretion into bile occurred. Mutant TR- rats have an inherited defect in the canalicular multispecific organic anion transporter, which mediates the ATP-dependent secretion of a wide range of organic anions over the canalicular membrane into bile. When cultured Wistar and TR- hepatocytes were loaded with glutathione bimane, both cell types displayed a strong cytosolic fluorescence. Wistar cells completely lost this cytosolic fluorescence at incubation on monochlorobimane free medium because of secretion of glutathione bimane. A clear punctate fluorescence remained, however, which was scattered through the cell with some perinuclear concentration. In some cells vesicular fluorescence was also concentrated around a canaliculus. In contrast, TR- cells lost their cytosolic fluorescence more slowly and completely lacked the vesicular fluorescence. Making cells selectively permeable with digitonin directly after loading them with glutathione bimane to remove cytosolic fluorescence again revealed the presence of fluorescent vesicles in Wistar cells and their absence in TR- cells. In Wistar cells vesicular fluorescence could be increased by preincubation with monensin or methylamine, compounds that have been shown to interfere with plasma membrane recycling. In conclusion, these results suggest that apart from secretion over the plasma membrane, the canalicular multispecific organic anion transporter may be involved in accumulation of organic anion in intracellular vesicles. It is hypothesized that this intracellular localization of the canalicular multispecific organic anion transporter is caused by recycling of the transporter between the plasma membrane and intracellular membranes. PMID- 8444419 TI - Effects of dietary cholesterol on bile formation and hepatic processing of chylomicron remnant cholesterol in the rat. AB - We have studied the coupling between hepatic uptake of chylomicron remnant cholesteryl ester and biliary excretion of cholesterol and bile acids in rats, after feeding them a cholesterol-free (control) or a high-cholesterol diet (1% wt/wt) for 2 wk. We equipped rats with permanent catheters in the bile duct, duodenum and heart to allow experiments in unanesthetized, unrestrained animals. Cholesterol feeding induced a 20% increase in plasma cholesterol concentration, a threefold increase in hepatic bile acid synthesis and a 27% increase in bile acid pool size, whereas biliary excretion of cholesterol was decreased by 50%. The enlarged bile acid pool contained relatively less cholic acid and more chenodeoxycholic acid and muricholic acids. [3H]cholesteryl ester-labeled chylomicron remnants (150 micrograms protein per rat) were injected intracardially, and blood and bile were collected for a period of 22 hr. Plasma disappearance of remnants was significantly delayed by cholesterol feeding, probably caused by competition with diet-induced beta-very low density lipoproteins for hepatic uptake. In control rats biliary excretion of chylomicron remnant-derived radioactivity (50% in free cholesterol and 50% in bile acids) showed an initial peak 1 hr after injection (2.4% dose per hour). A second peak (90% in bile acids), amounting to 1.5% of the dose per hour, appeared 11 hr after injection. Total 22-hr excretion of 3H was 22% of the dose. In cholesterol-fed rats chylomicron remnant-derived radioactivity appeared more rapidly in bile, with a peak 1 hr after injection, amounting to 3.5% of the dose per hour. In this case radioactivity was mainly present as bile acid. Total excretion in 22 hr was 27% of the dose. We conclude that chylomicron remnant uptake by the liver is efficiently coupled to bile acid synthesis and biliary excretion, thus providing an efficient pathway for removal of intestine-derived cholesterol. After cholesterol feeding, chylomicron remnant cholesteryl ester is more efficiently converted to bile acids, a mechanism which may contribute to the resistance of rats to diet-induced elevation of plasma cholesterol. In contrast, biliary excretion in the form of free cholesterol, the second main excretory pathway, is significantly decreased by a high-cholesterol diet. PMID- 8444420 TI - Dissection of compartments in rat hepatocytes involved in the intracellular trafficking of high-density lipoprotein particles or their selectively internalized cholesteryl esters. AB - The trafficking of apolipoprotein E-deficient high-density lipoprotein particles and of their component cholesteryl esters in rat hepatocytes was studied. Human high-density lipoprotein 3, labeled with two nondegradable, intracellularly trapped tracers in their apolipoprotein A-I and their cholesteryl esters, were injected into rats, and five subcellular hepatocytic fractions were isolated at various time intervals. In control experiments with homologous lipoproteins, doubly labeled rat high-density lipoproteins depleted of apolipoprotein E were used. In endosomes and lysosomes the two labels were recovered at near unity, indicating that high-density lipoproteins are endocytosed as particles, transported to early and late endosomes and finally subjected to lysosomal degradation. No significant amounts of label were found in receptor-recycling endosomes. In contrast to label of those of low-density lipoproteins, label of component protein and cholesteryl esters of high-density lipoproteins from isolated endosomes floated at different densities in gradient ultracentrifugation, indicating early disintegration of high-density lipoprotein particles. In contrast to the endocytic organelles, in the whole liver, label of high-density lipoprotein-associated cholesteryl esters exceeded the label of high density lipoprotein-associated apolipoprotein A-I twofold to threefold. This finding is compatible with selective uptake of high-density lipoprotein cholesteryl esters in addition to uptake of high-density lipoprotein particles. The excess cholesteryl esters accumulated in a nonendosomal fraction, whose major proteins differed from the integral proteins of endosomes. These data suggest two distinct intracellular routes of hepatocytic high-density lipoprotein trafficking in vivo. High-density lipoproteins free of apolipoprotein E are internalized intact by hepatocytes, are predominantly transported to early and late endosomes and are finally subjected to lysosomal degradation. High-density lipoprotein particles do not undergo retroendocytosis in hepatocytes. In addition, high density lipoprotein-associated cholesteryl esters can be taken up by hepatocytes selectively. They, however, accumulate in a nonendosomal, nonlysosomal compartment. PMID- 8444421 TI - A rapid method to study heterogeneous gene expression in liver by direct assay of messenger RNA from periportal and perivenous cell lysates. AB - To study zonation of liver gene expression, we obtained periportal or perivenous rat liver cell lysates virtually devoid of nuclear material by site-directed digitonin infusion in situ. Total RNA was isolated, messenger RNAs were reverse transcribed and complementary DNAs were assayed after polymerase chain reaction mediated amplification. The zonal distribution of messenger RNAs of alcohol dehydrogenase (little zonation), glutamine synthetase (perivenous) and cytochrome P-450 2E1 (perivenous) messenger RNAs, as analyzed by this technique, were found to be similar to the distribution of corresponding apoproteins. Using appropriate primers or complementary DNAs, zonation of many different messenger RNAs can be determined from the same sample by this simple and rapid method. PMID- 8444422 TI - A scanning electron microscopic study of liver microcirculation disarrangement in experimental rat cirrhosis. AB - Hepatic microcirculation has been related to liver function in several studies. The principle of this relationship lies in the sequential distribution of blood from the feeding vessels of the hepatic acinus to the central vein. This study was undertaken to investigate the progressive changes at different sites of the liver microvascular bed in the developing cirrhosis, both by light microscopy and scanning electron microscopy of corrosion casts. Experimental cirrhosis was induced with intragastric carbon tetrachloride. The most important vascular changes progressively observed are the reduction of the distance between the pre- and postsinusoidal vessels, the presence of newly formed shunting vessels bypassing the sinusoids and, finally, the development of a perinodular vascular plexus composed of pre- and postsinusoidal vessels. Newly formed vessels grow through preformed tissue septa. These vascular modifications make any zonal gradient hardly possible. The loss of the zonal gradient of perfusion could highly modify liver function, along with the structural changes of hepatic laminae. Hepatocyte regeneration cannot recover the original vascular relationships: this makes the morphological and functional destructuralization of cirrhotic liver irreversible. PMID- 8444423 TI - Zonal changes of hepatobiliary taurocholate transport in intrahepatic cholestasis induced by 17 alpha-ethinyl estradiol: a histoautoradiographic study in rats. AB - The liver has a great reserve capacity for hepatobiliary bile salt transport. This study was performed to elucidate the significance of this capacity in ethinyl estradiol-induced cholestasis by direct visualization of the zonal involvement in taurocholate transport. The acinar distribution of [3H]taurocholate was determined by histoautoradiographical study of cryopreserved liver slices in normal rats and rats treated with ethinyl estradiol for 5 days. Silver grain densities over the different acinar zones were estimated on digitized image analysis. In control animals, histoautoradiographical study performed 4 min after the start of perfusion showed restriction of taurocholate to acinar zone 1. In contrast, in ethinyl estradiol-treated animals, taurocholate was also found in zone 2 and, in smaller concentrations, in zone 3. In control animals, the relative blackenings by silver grains of acinar zones 1, 2 and 3 were 66% +/- 1.2%, 25% +/- 1.6% and 5% +/- 0.6%, respectively. After 5 days of ethinyl estradiol treatment, blackenings were 58% +/- 1.5%, 36% +/- 2.1% and 12% +/- 0.8%, respectively. As early as 15 sec after injection of [3H]taurocholate, the bile canalicular areas of the cell plates and the bile ductules of ethinyl estradiol-treated animals were labeled as intensely as those of control animals. Our results demonstrate ethinyl estradiol-induced recruitment of the acinar zones 2 and 3 for hepatobiliary taurocholate transport. This recruitment may largely compensate for reduction of transport capacity of periportal hepatocytes in early cholestasis. PMID- 8444424 TI - Atrial natriuretic factor and liver disease. AB - A working formulation for the role of ANF in the sodium retention of cirrhosis is summarized in Figure 4. Sodium retention is initiated early in cirrhosis, either as a result of hepatic venous outflow block or of primary vasodilation. The consequent intravascular volume expansion causes increases in ANF levels. At this stage of disease, the rise in ANF level is sufficient to counterbalance the antinatriuretic influences. However, this occurs at the expense of an expanded intravascular volume with the potential for overflow ascites. With progression of disease, disruption of intrasinusoidal Starling forces and loss of volume from the vascular compartment into the peritoneal compartment occur. This underfilling of the circulation may attenuate further increases in plasma ANF and promotes the activation of antinatriuretic factors. At this later stage of disease, elevated levels of ANF are insufficient to counterbalance antinatriuretic influences. Thus the role of ANF in cirrhosis is primarily beneficial in that it successfully attenuates the antinatriuretic forces in the compensated stage. Raised ANF levels have two potential deleterious effects. First, ANF may exacerbate arterial vasodilation, leading to further sodium retention. The primacy of vasodilatation has been proposed as an alternate formulation to the overflow and underfill hypotheses. Second, Epstein et al. found higher basal ANF levels in cirrhotic patients with edema than in those patients without edema. ANF is known to reduce plasma volume in anephric animals and to increase the ultrafiltration coefficients of isolated capillaries. Therefore it is conceivable that in the clinical setting in which antinatriuretic factors limit the renal responsiveness to ANF but in which ANF levels are elevated (i.e., cirrhosis, congestive heart failure, primary kidney disease), ANF itself may contribute to edema formation at the level of the peripheral microcirculation. In general, ANF likely has no primary role in the sodium retention in cirrhosis. In early compensated cirrhosis, ANF may maintain sodium homeostasis despite the presence of mild antinatriuretic factors. In late ascitic cirrhosis renal resistance to ANF develops, rendering it ineffective.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8444425 TI - Abnormal splanchnic and systemic hemodynamics of end-stage liver disease: what happens after liver transplantation? PMID- 8444427 TI - Extracorporeal ultrafiltration and intravenous reinfusion of ascitic fluid vs. large-volume paracentesis: a randomized controlled trial. PMID- 8444426 TI - Acute hepatitis A: an endangered species. PMID- 8444428 TI - Spanning boundaries in public psychiatry. PMID- 8444430 TI - Setting new standards for social work case management. PMID- 8444429 TI - The need for asylum revisited. PMID- 8444431 TI - Examining criteria for panic disorder. PMID- 8444432 TI - Changing characteristics of schizophrenic patients admitted to state hospitals. AB - OBJECTIVE: Characteristics of schizophrenic patients admitted to state hospitals between 1970 and 1986 were studied to examine changes in the demographic profile of the patient population and in principal sources of payment for hospitalization over the study period. METHODS: Information on patients' demographic characteristics and principal payment sources was obtained from a nationally representative data base compiled about every five years by the National Institute of Mental Health. RESULTS: Among schizophrenic patients admitted between 1970 and 1986, the proportion of African-American males increased. By 1986 patients were less likely to pay for care through private insurance or their own resources. They were more likely to receive Medicare and to lack medical insurance. Medicare use increased largely among white patients, and medical indigency largely among African-American patients. CONCLUSIONS: Changes in the characteristics of schizophrenic patients admitted to state hospitals between 1970 and 1986 may be related to changes in nosology, in the prevalence of schizophrenia, and in the types of patients likely to be admitted to state hospitals. The increase in the number of medically indigent patients accentuates the need for more adequate finding of state hospitals. PMID- 8444433 TI - Patients' perceptions of their quality of life 11 years after discharge from a state hospital. AB - OBJECTIVE: Fifty-three state hospital patients discharged to group homes in the community in 1978-79 were followed up at three and 11 years to assess their quality of life and several other dimensions of their community experience. METHODS: A structured interview was used to obtain data on patients' perceptions of and degree of satisfaction with aspects of their lives one month before hospital discharge and at three and 11 years after. Group home staff rated patients' functioning at follow-up. Data on rehospitalizations over the 11-year period were collected. RESULTS: At 11-year follow-up, 30 of the surviving 40 patients were living in noninstitutional settings: nine in independent or semi independent settings and 21 in group homes. The 30 patients perceived that their quality of life outside the hospital had improved in several ways, including the extent of their social networks, the quality of their living environment, and their capacity to meet basic needs. When data were averaged over the 11 years and corrected for the shorter time in the study of subjects who died, patients spent only 2.6 percent of the follow-up period in the hospital. Only one patient at 11 years wanted to return to the hospital. CONCLUSIONS: The finding that even the small minority of patients who required multiple rehospitalizations preferred community life may have important clinical and policy implications for setting the threshold of hospital discharge. PMID- 8444434 TI - Quality of care and outcomes of chronic mentally ill patients in hospitals and nursing homes. AB - OBJECTIVE: Quality of care in three types of facilities in which chronic mentally ill patients reside was examined to determine how it was related to patient functioning and to determine how patients' dependency on others for self-care moderated relationships between quality of care and patient functioning. METHODS: Discriminant function analyses and multiple regression analyses were used to examine 12-month follow-up data from a Department of Veterans Affairs (VA) study of 294 chronic mentally ill patients in 52 community nursing homes, nine VA nursing home care units, and 43 VA hospital psychiatric units. RESULTS: The three types of facilities were best differentiated by staff and resident characteristics and facility policies. Residents of community nursing homes were more impaired, and staff were less well trained, than in the VA facilities. The community nursing homes had less restrictive policies. Patients who lived in facilities that gave them more control over their daily lives and that had larger proportions of high-functioning patients reported more life satisfaction and vigor. Patients in facilities with more social and recreational activities reported less life satisfaction. The extent to which facility features were beneficial or harmful was related to patients' self-care dependency. Supportive physical features and living-assistance services tended to aid impaired residents, whereas more experienced staff and policies that promoted control by residents tended to aid independent residents. CONCLUSIONS: Program managers may need to tailor facility environments to patients' level of functioning to maximize beneficial effects. PMID- 8444435 TI - Correlates of patterns of substance abuse among patients with schizophrenia. AB - OBJECTIVE: Most previous research on substance abuse among patients with schizophrenia has not considered the types of substances abused or the confounding influences of polysubstance abuse. The authors' goals were to identify patterns of substance abuse among a sample of subjects with schizophrenia and to determine demographic and clinical correlates of these patterns. METHODS: Subjects with schizophrenia were identified from the Epidemiologic Catchment Area study data base, which also provided information on the types of substances abused and on selected demographic and clinical characteristics. Latent class analysis was used to group subjects based on their patterns of substance abuse. Logistic regression was used to identify demographic and clinical correlates of the patterns. RESULTS: Three latent classes based on patterns of substance abuse were identified: no substance abuse, abuse of alcohol and cannabis, and polysubstance abuse. Subjects with either of the two patterns of substance abuse were more likely to be younger and male and to have depressive symptoms. CONCLUSIONS: The results do not support a link between abuse of specific substances and specific clinical symptoms but do suggest a general link between substance abuse and affective disturbance among schizophrenic patients. PMID- 8444436 TI - Characteristics of emergency room patients that predict hospitalization or disposition to alternative treatments. AB - OBJECTIVE: The purpose of the study was to identify variables that predicted three different dispositions of patients seen in a psychiatric emergency room: hospitalization, an emergency housing program, and an outpatient crisis program. METHODS: Social, psychiatric, demographic, and vocational characteristics of 50 patients in each disposition group were examined to learn whether they varied sufficiently to explain the different dispositions. RESULTS: Patients in the hospitalized group were most psychologically impaired and those in the crisis program group least impaired. Patients referred to emergency housing were more moderately impaired but not always significantly different in impairment from hospitalized patients. Discriminant analysis yielded a model of 11 variables whose combined effect accounted for 79 percent of the variance. Psychiatric determinants were the most important predictors, although social, vocational, and demographic variables were also significant. Using these predictors, 76 percent of the original sample and 63 percent of a cross-validation sample were correctly classified by disposition group. CONCLUSIONS: The results confirmed the importance of psychiatric determinants in the dispositional process. The similarity between hospitalized patients and those assigned to emergency housing suggests that some hospitalized patients would be good candidates for alternative treatment. PMID- 8444437 TI - Characteristics of suicides by inmates in an urban jail. AB - OBJECTIVE: The authors' goals were to describe the characteristics of suicides committed by inmates in custody of the New York City Department of Correction between 1980 and 1988. METHODS: Data on suicides were collected from records of the jail health services, the municipal medical examiner's office, and the city's prison death review board, as well as from reports of the New York State Commission of Correction and other documents. RESULTS: The authors identified 48 suicides committed by inmates during the study period. Forty-two percent of the suicides occurred within the first 30 days of incarceration, and 50 percent occurred within three days of a court appearance. More than 90 percent of suicides were by hanging. Ninety-one percent of suicides took place in cells in which the inmate was housed alone. Fifty-two percent of the inmates who committed suicide had a major psychiatric diagnosis, and 46 percent had a history of inpatient or outpatient psychiatric care. CONCLUSIONS: The authors recommend that all inmates with a psychiatric history or potential suicidality be identified and linked with ongoing mental health services while incarcerated, that potentially suicidal inmates never be housed alone in a cell, and that correctional staff be trained to recognize potentially self-destructive inmates and to prevent suicide. PMID- 8444438 TI - A consultative study as a catalyst for improving mental health services for rural children and adolescents. AB - The consultative study is one model of academic involvement in public mental health services. However, the effects of consultation and how it acts as a catalyst for change have been poorly documented. The authors describe a consultative study in which a team from a academic training center examined the system of mental health and related human services for children and adolescents in a semirural county in western Pennsylvania. They also present results of a six year follow-up survey assessing the study's effects. Improvement in the system of care during the follow-up period included creation and maintenance of a children's unit and a partial hospital program for adolescents at the country's community mental health center. The consultative study and the follow-up survey were instrumental in establishing a comprehensive range of services, including intensive case management for severely disturbed youngsters and a home-based mental health services program. PMID- 8444439 TI - From research to clinical practice: dissemination of New York State's family psychoeducation project. AB - The New York Family Support Demonstration Project was begun in 1984 to translate the results of research on family psychoeducation in the treatment of schizophrenia into general practice. Goals were to compare experimentally a single-family psychoeducation model with a multiple-family group format, to replicate successful outcomes in ordinary clinical settings, and to train agency clinicians in the model. A total of 172 schizophrenic patients and their families from six sites across the state were followed for two years. Relapse rates comparable to those in more narrowly focused research studies were obtained in ordinary clinical settings. Patients in the multiple-family format had substantially lower risk of relapse than patients in single-family treatment. Over the next three years, the multiple-family approach was successfully disseminated across the state using a strategy based on five central assumptions of the psychoeducational model. PMID- 8444440 TI - Initial evaluation of reorganized hospitalization services in a community mental health center. AB - OBJECTIVE: Two locked inpatient units at an inner-city community mental health center were reorganized as a hospitalization service consisting of a 22-bed intensive care inpatient unit, an acute-treatment day hospital for 20 patients, and a 23-bed transitional residence program. Levels of functioning of hospitalized patients treated before and after the reorganization were compared to determine if the reorganized program as a whole was more effective clinically than the two inpatient units had been. METHODS: The authors retrospectively compared levels of functioning at discharge of random samples of 10 percent of patients treated in the ten months before the reorganization (N = 66) and 10 percent of the intensive care and day hospital patients treated in the same ten calendar months afterward (N = 78). They also compared data on episodes of seclusion and restraint and on patient flow in the two time periods. RESULTS: The mean functional level of intensive care and day hospital patients treated in the reorganized service was significantly higher than the level of inpatients treated before. The mean duration of episodes of seclusion, but not of restraint, decreased significantly. Total service admissions and readmissions increased from 493 to 603. CONCLUSIONS: The reorganized service encouraged patients to function at higher levels. However, such a program must be affiliated with a diversified and well-functioning outpatient service that can divert some potential inpatients to appropriate alternative treatments and help move patients out of the day hospital-residential program when they are stabilized. PMID- 8444441 TI - Daily hassles of persons with severe mental illness. PMID- 8444443 TI - Guidelines for disclosure of patient information under the Americans With Disabilities Act. PMID- 8444442 TI - Work capacity in schizophrenia. PMID- 8444444 TI - HIV seroprevalence among long-stay patients in a state psychiatric hospital. PMID- 8444445 TI - Medical findings in school-age psychiatric inpatients grouped by public and private payment. PMID- 8444446 TI - Housing patterns of homeless mentally ill persons receiving assertive treatment services. PMID- 8444447 TI - Multiple personality disorder. PMID- 8444448 TI - Adjustment reactions. PMID- 8444450 TI - Mental health share of state health and welfare spending dropped between 1981-90, study shows. PMID- 8444449 TI - Choice of provider. PMID- 8444451 TI - APA updates guidelines for care of HIV-infected inpatients, confidentiality and disclosure of HIV. PMID- 8444452 TI - Fast forward into the future. PMID- 8444453 TI - Remapping health care delivery. Multihospital system execs scope out the post reform delivery world--and their place in it. Roundtable discussion. PMID- 8444454 TI - Rural views on reform. Rural execs see challenges, contradictions ahead. PMID- 8444455 TI - Leeway for states. Revised waiver process may encourage state experiments. AB - State government leaders are encouraged by President Clinton's promise to streamline the Medicaid waiver process. But how much and what kind of new activity will result depends on how far he goes in loosening current standards. PMID- 8444456 TI - No longer a luxury. More and more, hospitals recognize the necessity of offering child care benefits to employees. PMID- 8444457 TI - Primary care push. Teaching hospitals start programs to enhance MD base. PMID- 8444458 TI - Hospitals, suppliers put TQM to the test. PMID- 8444459 TI - CEOs: trustees need financial savvy. PMID- 8444460 TI - Hospital develops system to track indigent care. PMID- 8444461 TI - GAO highlights obstacles to Medicaid enrollment. PMID- 8444462 TI - Data watch. Managed care penetration differs by market. PMID- 8444463 TI - Three principles make the case for reform. PMID- 8444464 TI - An alphoid DNA sequence conserved in all human and great ape chromosomes: evidence for ancient centromeric sequences at human chromosomal regions 2q21 and 9q13. AB - Using vector-CENP-B box polymerase chain reaction (PCR) we isolated and cloned from a human chromosome 21-specific plasmid library, a 1 kb DNA sequence, named p alpha H21. In in situ hybridization experiments, p alpha H21 hybridized, under high stringency conditions, to the centromeric region of all the human, chimpanzee, gorilla and orangutan chromosomes. On human chromosomes p alpha H21 also identified non-centromeric sequences at 2q21 (locus D2F33S1) and 9q13 (locus D9F33S2). The possible derivation of these sequences from ancestral centromeres is discussed. Sequence analysis confirmed the alphoid nature of the whole p alpha H21 insert. PMID- 8444465 TI - Detection of complete and partial chromosome gains and losses by comparative genomic in situ hybridization. AB - Comparative genomic in situ hybridization (CGH) provides a new possibility for searching genomes for imbalanced genetic material. Labeled genomic test DNA, prepared from clinical or tumor specimens, is mixed with differently labeled control DNA prepared from cells with normal chromosome complements. The mixed probe is used for chromosomal in situ suppression (CISS) hybridization to normal metaphase spreads (CGH-metaphase spreads). Hybridized test and control DNA sequences are detected via different fluorochromes, e.g., fluorescein isothiocyanate (FITC) and tetraethylrhodamine isothiocyanate (TRITC). The ratios of FITC/TRITC fluorescence intensities for each chromosome or chromosome segment should then reflect its relative copy number in the test genome compared with the control genome, e.g., 0.5 for monosomies, 1 for disomies, 1.5 for trisomies, etc. Initially, model experiments were designed to test the accuracy of fluorescence ratio measurements on single chromosomes. DNAs from up to five human chromosome specific plasmid libraries were labeled with biotin and digoxigenin in different hapten proportions. Probe mixtures were used for CISS hybridization to normal human metaphase spreads and detected with FITC and TRITC. An epifluorescence microscope equipped with a cooled charge coupled device (CCD) camera was used for image acquisition. Procedures for fluorescence ratio measurements were developed on the basis of commercial image analysis software. For hapten ratios 4/1, 1/1 and 1/4, fluorescence ratio values measured for individual chromosomes could be used as a single reliable parameter for chromosome identification. Our findings indicate (1) a tight correlation of fluorescence ratio values with hapten ratios, and (2) the potential of fluorescence ratio measurements for multiple color chromosome painting. Subsequently, genomic test DNAs, prepared from a patient with Down syndrome, from blood of a patient with T-cell prolymphocytic leukemia, and from cultured cells of a renal papillary carcinoma cell line, were applied in CGH experiments. As expected, significant differences in the fluorescence ratios could be measured for chromosome types present in different copy numbers in these test genomes, including a trisomy of chromosome 21, the smallest autosome of the human complement. In addition, chromosome material involved in partial gains and losses of the different tumors could be mapped to their normal chromosome counterparts in CGH-metaphase spreads. An alternative and simpler evaluation procedure based on visual inspection of CCD images of CGH-metaphase spreads also yielded consistent results from several independent observers. Pitfalls, methodological improvements, and potential applications of CGH analyses are discussed. PMID- 8444466 TI - Hypomelanosis of Ito in a girl with plexus papilloma and translocation (X;17). AB - We describe a de novo constitutional (X;17) (q13;p13 translocation in a girl with the clinical features of hypomelanosis of to and plexus papilloma. PMID- 8444467 TI - A null allele frequent in non-Jewish Tay-Sachs patients. AB - The molecular basis of null alleles was investigated by cDNA polymerase chain reaction (PCR) in seven Tay-Sachs patients. Although mRNAs were undetectable by Northern blot, cDNA-PCR amplification allowed us to get a sufficient amount of cDNA to characterize abnormal transcripts. In two French patients (one homozygote and one compound heterozygote with a 4-bp insertion in exon 11 of the second allele) suffering an infantile form of the disease, we detected abnormal RNAs with a 17-bp insertion due to a GT to AT transition at the donor site of intron 9, resulting in the activation of a cryptic donor site in the intron. This mutation has been found in 9 out of 82 Tay-Sachs chromosomes (11%) in association with alleles responsible from different clinical courses. In the other five patients we found the 4-bp insertion in exon 11 and two nonsense mutations. PMID- 8444468 TI - A single amino acid deletion in the alpha 2(I) chain of type I collagen produces osteogenesis imperfecta type III. AB - RNase A protection analysis was used in the search for the cause of a non-lethal osteogenesis imperfecta (OI) phenotype (Sillence type III). Cleavage of the hybrid formed between a normal alpha 2(I) sequence and RNA isolated from the patient indicated the presence of a mismatch. The position of the mismatch was determined and the corresponding area of COL1A2 was amplified using the polymerase chain reaction. Sequencing of cloned amplified DNA revealed the deletion, which was not present in either parent, of the final three bases of exon 19 in one of the patient's two COL1A2 alleles. The deletion results in the loss of amino acid 255 (a valine encoded by the last codon of exon 19) of the triple helical region of half of the alpha 2(I) collagen chains but does not disrupt the splicing of the heterogeneous nuclear RNA (hnRNA). This provides further evidence that OI type III may result from autosomal dominant mutations rather than only from autosomal recessive mutations as had previously been believed. PMID- 8444469 TI - Human breast cancer: frequent p53 allele loss and protein overexpression. AB - A sample of 114 primary breast tumors and corresponding constitutional DNA were tested for loss of heterozygosity (LOH) of the YNZ22 and p53 genes, both located in the 17p13 region. Loss of the p53 allele was found in 28 of 44 primary breast carcinomas (64%). In contrast LOH in only 26 of 61 tumors (43%) was detected with the variable number of tandem repeats (VNTR) probe YNZ22 mapping at 17p13.3 close to the p53 locus at 17p13.1. Among 19 tumors informative for both probes allele loss at 17p13.3 never occurred without p53 involvement. These data suggest, that p53 is the target of 17p13 allelic deletions in human breast cancer. Immunohistochemistry showed overexpression of the p53 protein in 25 of 50 cases (50%) presumably reflecting activating point mutations. Overexpression was not correlated with allele loss but seemed to be closely related to the presence of point mutations in this study. No homozygous deletions or rearrangements of the p53 gene were detected. This would argue for an important role of heterozygous p53 mutations in human breast cancer. PMID- 8444470 TI - An alpha-spectrin mutation responsible for hereditary elliptocytosis associated in cis with the alpha v/41 polymorphism. AB - The alpha 207 Leu-->Pro mutation in spectrin has recently been identified as a cause of alpha I/50-46a hereditary elliptocytosis (HE) or pyropoikilocytosis among Black people. We have found this mutation in a Moroccan family in both the heterozygous and homozygous states. The mutated alpha-spectrin allele carried, in cis, the alpha V/41 polymorphism, a common polymorphism altering the peptide maps and associated with a low-expression level. This is the first report of the cis combination of an HE mutation and the alpha V/41 polymorphism. Presumably, such a combination accounts for the very low expression of the abnormal allele in the heterozygous state. PMID- 8444471 TI - Regional assignment of the gene coding for a human Graves' disease autoantigen to 10q21.3-q22.1. AB - A cDNA coding for a human Graves' disease autoantigen (hGT) has been isolated from a thyroid expression library. Using this cDNA as a probe, the gene for hGT, previously assigned to chromosome 10, has been further localized to 10q21.3-q22.1 by non-isotopic in situ hybridization. PMID- 8444472 TI - Genetic and population study of a Y-linked tetranucleotide repeat DNA polymorphism with a simple non-isotopic technique. AB - A polymorphic microsatellite (Y-27H39) based on a (GATA)n repeat was recently discovered on the short arm of the human Y chromosome. We have used a simple technique based on polymerase chain reaction amplification and native polyacrylamide gel electrophoresis followed by highly sensitive silver staining to study the inheritance, the genetic stability and the allele frequency distribution of this polymorphism in the Brazilian population. We have analyzed 100 randomly chosen Caucasian Brazilian father-son pairs with established paternity. Five alleles, four base-pairs apart, were easily distinguishable. Their frequencies were: A (186 bp), 0.19; B (190 bp), 0.49; C (194 bp), 0.24; D (198 bp), 0.07; E (202 bp), 0.01. In all father-son pairs, there was complete allelic concordance. From these data, the probability of discrimination for forensic cases and the average probability of exclusion for paternity cases were both calculated to be 0.66. PMID- 8444473 TI - Physical mapping of microdeletions of the chromosome 17 short arm associated with Smith-Magenis syndrome. AB - We used probes from the juxta-centromeric region of the chromosome 17 short arm to map three microdeletions in patients with Smith-Magenis syndrome. The common clinical findings were: speech delay with behavioural problems associated with broad flat midface, brachycephaly, broad nasal bridge and brachydactyly. We demonstrated, using Southern blot analysis (loss of heterozygosity and gene dosage), that all patients were deleted for two p11.2 markers: pYNM 67-R5 (D17S29) and pA10-41 (D17S71). We determined that one breakpoint was located between D17S58 and D17S29 and the other breakpoint distal to D17S71. The possibility that an unstable region, located between the Smith-Magenis syndrome locus and CMT1A a closely located locus, could be involved in the rearrangements associated with these two inherited diseases is discussed. PMID- 8444474 TI - Routine diagnosis of DiGeorge syndrome by fluorescent in situ hybridization. AB - In a series of ten patients affected by DiGeorge syndrome, we screened, by high resolution banding and fluorescent in situ hybridization of a cosmid probe, for microdeletions associated with this syndrome. In the ten patients, a microdeletion was demonstrated by in situ hybridization, but suspected only in two patients by high resolution banding. PMID- 8444475 TI - A sequence variation in the human cystatin D gene resulting in an amino acid (Cys/Arg) polymorphism at the protein level. AB - A polymorphism in the coding region of the human cystatin D gene has been detected by direct sequencing of amplified DNA from different individuals. The variation, resulting from a T/C transition in exon 1 of the gene, causes an amino acid variation, Cys/Arg, at the protein level. An allele-specific oligonucleotide hybridization assay was developed and used to demonstrate this polymorphism in the population. the deduced frequencies were 0.55 and 0.45 for the Cys and Arg variant-encoding alleles, respectively. PMID- 8444476 TI - HIV prevalence among clients attending a sexually transmitted diseases clinic in Amsterdam: the potential risk for heterosexual transmission. AB - INTRODUCTION: Patients attending a clinic for sexually transmitted diseases (STD) in general have engaged in at risk sexual behaviour. Therefore they are at increased risk of acquiring HIV through sexual contact. OBJECTIVE: To determine the HIV prevalence among patients attending a STD clinic in Amsterdam. METHODS: An anonymous cross sectional study was conducted in two 5-week periods in Spring and Autumn 1991. RESULTS: Of the 2362 patients attending the clinic during the study period, 2292 (97%) consented to participate; of these, 2138 (93%) were interviewed and anonymously tested, while 154 (7%) consented to be interviewed but refused HIV antibody testing. The HIV prevalence was 4.2% (90/2138); 93% of seropositive participants reported homosexual contacts and/or intravenous use of drugs (IVDU). HIV prevalence among heterosexual non-IVDU men was 0.5% and among non-IVDU women 0.1%. Among all heterosexually active participants, including IVDU and bisexual men, the HIV prevalence was 1.5%. The 28 of 90 HIV infected participants that were heterosexually active reported together approximately 135 heterosexual partners in the six months preceding the study; 13 of these 28 heterosexually active participants had a STD diagnosed at their present clinic visit, while four (30%) of them already knew they were HIV infected. CONCLUSIONS: From these data we conclude that there is a substantial risk of further transmission of HIV through heterosexual contact. In order to try to reduce this potential for further sexual transmission of HIV, services offered by the STD clinic should not only include voluntary confidential counselling and HIV testing, but also notification of partners of HIV infected clinic-attendants. Finally, we conclude that anonymous HIV prevalence studies that link HIV test results to risk behaviour for HIV infection can be performed with a high rate of participation. Repeating such prevalence studies in time can help in monitoring the HIV incidence in the heterosexually active population. PMID- 8444477 TI - The testing of saliva samples for HIV-1 antibodies: reliability in a non-clinic setting. AB - AIMS: To assess the reliability of saliva samples as a means of testing for HIV antibodies outside clinic settings. METHODS: Men taking part in a non-clinic longitudinal study of homosexually active men provided samples of saliva and blood. Sera were screened using a competitive ELISA (Wellcozyme) and positive sera were confirmed by an indirect ELISA (Abbott). Saliva samples were screened either using an IgG captive radioimmunoassay or an amplified ELISA. RESULTS: A total of 534 paired saliva and blood samples were tested. Overall sensitivity was 96.2% and specificity was 100%. None of the saliva tests were falsely positive for HIV-1 antibodies. CONCLUSIONS: HIV-1 saliva tests can reliably be used in a non-clinic or field setting. However, if results are to be given to respondents, it is necessary to offer adequate counselling and consider the mechanisms for referral and follow-up for those that are found to be HIV-1 antibody positive. PMID- 8444478 TI - Sexually transmitted diseases in nineteenth and twentieth century India. PMID- 8444479 TI - The prevalence of human retroviral infections in female patients attending a central London sexually transmitted disease clinic: 1985-1990. AB - OBJECTIVES: To determine the prevalence of infection with HIV-1, HIV2, HTLV-1 and HTLV-2 in female attenders at a central London sexually transmitted disease clinic in an 8 week period in 1989-1990, and compare it with similar samples studied between 1985 and 1987. DESIGN: Anonymous testing of serum samples from consecutive female patients having routine serological investigation for syphilis. Testing was for clinically important retroviruses, Hepatitis B core antibodies (anti-HBc), and p24 and reverse transcriptase (RT) antigens. Age (in 5 year bands), nationality (in broad geographical zones), diagnosis on the day of presentation, and history of intravenous drug usage were recorded for each patient. Annual gonorrhoea rates were analysed from 1981 to 1990. SETTING: Outpatients of the department of genitourinary medicine. PATIENTS: A total of 850 females attending consecutively and having routine syphilis serology. MAIN RESULTS: The prevalence of anti-HIV-1 in female attenders in 1989-1990 was 0.35% (3/850). Prevalence in the same clinic has remained statistically unchanged since the first female cases were identified in 1986. No cases of HIV-2, HTLV-1 or HTLV 2 were identified, and no early HIV-1 infection evidenced by the presence of p24 or RT antigenaemia was found. Female gonorrhoea rates continued to decline but other STD monthly/annual rates have remained unchanged. CONCLUSIONS: Over the last 5 years prevalence of HIV-1 infection in females in our clinic has remained unchanged and other retroviral infections have remained absent. However, the unaltered rates of other genital infections, their potential role in the heterosexual spread of HIV-1 infection, and the lack of evidence for any major changes in female sexual behaviour suggests there is a need to remain vigilant. This work complements the MRC multicentre, unlinked, genitourinary medicine clinic, anonymous testing programme, and our group will continue to apply this simple methodology to specimens from female attenders to contribute to the surveillance of the evolving HIV-1 epidemic. PMID- 8444480 TI - Contact-independent cytotoxicity of Trichomonas vaginalis. AB - OBJECTIVE: To test the dependency of haemolytic and cytocidal manifestations of pathogenicity of Trichomonas vaginalis on direct contact between the target cells and the organism. TEST ORGANISM: T vaginalis strain Baltimore 42. DESIGN: Haemolysis in the presence of live T vaginalis and of its filter-sterilised metabolic products was compared. The dependence of haemolytic and cytocidal effects on retention of low pH of metabolic products of the organism was demonstrated by parallel titrations of sterile filtrates in normal saline and in phosphate buffered saline (PBS) pH 7.0. RESULTS: Near complete lysis was obtained when erythrocytes mixed with T vaginalis were incubated for 1 h at 37 degrees C in saline containing 1% glucose. The same degree of haemolysis was present in filter-sterilised glucose-saline in which the organism was incubated (1 h/37 degrees C) before erythrocytes were added and incubated under the same conditions as in the mixture with the organism. The degree of haemolysis in filtrates was dependent on retention of low pH (below 5.0) of the suspending fluid in which the organism alone was incubated. Dilution of filtrates in PBS, as opposed to normal saline, abolished or diminished the haemolytic effect. Presence of glucose (energy source) in the saline during incubation of the organism had a pronounced enhancing effect. The production of haemolytic metabolites was temperature dependent, whereas the haemolytic process per se was not. The effect was not an exclusive property of T vaginalis since it was also demonstrated with other trichomonads. The same filtrates applied to tissue culture exerted cytocidal effect strikingly similar to that observed in the haemolysis experiments. CONCLUSION: Neither haemolytic nor cytocidal effect of T vaginalis was contact dependent. PMID- 8444481 TI - A comparison of yield from cervix versus vagina for culturing Candida albicans and Trichomonas vaginalis. AB - OBJECTIVE: To determine the agreement of culture results of Candida albicans and Trichomonas vaginalis from the cervix versus posterior fornix in women with vaginal symptoms. DESIGN: Same patient comparison of culture results from two sample sites. SETTING: Twenty one general practices in Amsterdam and the east of the Netherlands. SUBJECTS: Six hundred and eighty two women aged 15 to 55 years with vaginal symptoms, seen between 1 October 1987 and 31 May 1990. MAIN OUTCOME MEASURES: For each site (cervix and posterior fornix) the proportion of detected C albicans and T vaginalis. The sensitivity of the cervical swab related to the vaginal one. The percentage of concordance for both microorganisms. RESULTS: In 248 (34%) women C albicans was diagnosed and in 38 (6%) T vaginalis. In 99% of the proven C albicans cases, the yeast was found in the vagina. In 94% C albicans was isolated from the cervix. Sensitivity of the cervical swab was 94%. In 98% of the patients a concordant observation was made regarding detection of yeast. In 97% of the proven T vaginalis cases the protozoon was found in the vagina. In 91% T vaginalis was detected from the cervical swab. Sensitivity of the cervical swab was 92%. The culture results were concordant in 99%. CONCLUSION: The yield from the vaginal source was slightly better than that from the cervix for culture of both microorganisms. For screening purposes, specimen-collection for culture of N gonorrhoeae, C albicans and T vaginalis can be combined in one swab taken from the cervix. PMID- 8444482 TI - Evaluation of an enzyme-linked immunoassay and confirmatory test for the detection of Chlamydia trachomatis in male urine samples. AB - First pass urine (FPU) samples were compared with urethral swab culture from 304 males attending a genitourinary medicine clinic using an enzyme immuno assay (EIA). All of the EIA positive samples were retested by incorporating a novel blocking reagent into the EIA protocol; 101 were positive by culture of which 83 were also positive by FPU EIA, an additional four were detected in FPU only and not by culture; 86 of these 87 were also confirmed positive by the blocking reagent. Discrepant results were evaluated by Syva MicroTrak. The sensitivity and specificity of FPU EIA as compared with urethral swab culture was 82.2% (83/101) and 98% (199/203) respectively with positive and negative predictive values of 95.4% (83/87) and 91.7% (199/217). Male urethral swab culture is more sensitive than FPU EIA; however, when culture is not available then FPU offers a reliable non-invasive alternative to swab EIA which may be of enormous benefit in community screening of asymptomatic as well as symptomatic patients. PMID- 8444483 TI - Urine and the laboratory diagnosis of Chlamydia trachomatis in males. AB - OBJECTIVE: To determine whether the use of urine samples from male patients can replace urethral swabs for the rapid detection of Chlamydia trachomatis by the Pharmacia EIA. SETTING: The STD clinic, Adelaide, South Australia. PATIENTS: There were two separate groups of male patients. Group A (398) patients provided urethral specimens for the EIA and culture tests. The patients in Group B (356) provided an urethral swab and a urine sample for the EIA test. METHODS: The urine samples and urethral swabs were tested for the presence of C trachomatis by the Pharmacia Chlamydia EIA. In addition, the urethral swabs from Group A patients were cultured for the organism by standard cell cultures. The infected cell cultures were identified by an immunofluorescence test using a FITC-monoclonal antibody to C trachomatis (Kallestad). RESULTS: When the EIA was validated against culture, it showed a sensitivity of 100% and a specificity of 95% with the urethral swabs from Group A patients. The urine specimens were positive in 24% of those patients who yielded a positive EIA result in the urethral swabs. CONCLUSIONS: Although the EIA test on urethral swabs showed high sensitivity and specificity when validated against culture, our results showed that the use of urine samples cannot replace urethral swabs for the laboratory diagnosis of this sexually transmitted disease. PMID- 8444484 TI - Actinomyces israelii in the female genital tract: a review. PMID- 8444485 TI - Outcome of cold coagulation for the treatment of cervical intraepithelial neoplasia in a department of genitourinary medicine. AB - OBJECTIVE: To evaluate the outcome of "cold coagulation" as a treatment modality for major grade cervical pathology, cervical intraepithelial neoplasia (CIN 2 and 3) in a department of genitourinary medicine. DESIGN: Prospective programme trial with 18 month follow-up of patients undergoing "cold coagulation" of the cervical transformation zone following colposcopic assessment and biopsy. SETTING: A genitourinary medicine colposcopy clinic. PATIENTS: 125 female patients with histologically proven major cervical pathology (CIN 2 and 3). The mean age of the patients was 24.5 years; 73% were unmarried, 43% currently smoked and 62% had a history of exposure to the human papilloma virus. MAIN OUTCOME MEASURES: Eradication of cervical abnormality with cytological findings at 4, 8 and 12 months and colposcopy at 18 months, with intervention colposcopic assessment if follow-up cytology was abnormal. RESULTS: Eradication of CIN was achieved in 96.5% of patients, the majority of treatment failures being detected at first cytology. Attendance for follow-up was good, with only a 16% default rate. Final colposcopy yielded five treatment failures. No major complications were noted. CONCLUSION: These results confirm that "cold coagulation" provides an acceptable, efficient and effective, low cost consumer friendly treatment for CIN 2 and CIN 3 in an out-patient genitourinary medicine colposcopy clinic. PMID- 8444487 TI - Paroxysmal cold haemoglobinuria in syphilis patients. PMID- 8444486 TI - STD in children: syphilis and gonorrhoea. PMID- 8444488 TI - Wassermann reaction in peripheral blood of patients with secondary syphilis and human-immunodeficiency virus infection. PMID- 8444489 TI - Oro-anal sex and the occurrence of Kaposi's sarcoma. PMID- 8444490 TI - Primary HIV-1 infection associated with prominent genital ulcers. PMID- 8444491 TI - Teenagers and the risk of STD. PMID- 8444492 TI - HIV infection in Tirupathi, India. PMID- 8444493 TI - National STD trends in Zambia 1987-89. PMID- 8444494 TI - Exophytic cervical warts--an indication for colposcopy? PMID- 8444496 TI - Seasonal variation in rheumatic heart disease. PMID- 8444495 TI - Pathogenesis of pelvic inflammatory disease. PMID- 8444497 TI - Platelet adhesion is related to heart rhythm disturbances in the acute phase of myocardial infarction. AB - This study examines the relationship between platelet adhesion, aggregation and the occurrence of heart rhythm disturbances in 43 consecutive patients (mean age 58) admitted to a coronary care unit with acute myocardial infarction. Blood for platelet studies was taken prior to institution of any medication and heart rhythm was monitored (Holter) for 24 h after admission. The control group consisted of 22 healthy subjects (mean age 55 yr). Platelet adhesion to collagen was measured in EDTA-platelet rich plasma by recording the changes in light transmission in an optical aggregometer. Platelet aggregation was measured by the Born method. Platelet adhesion was increased in the group of patients with acute myocardial infarction as compared to controls and was significantly higher in the patients with complex ventricular arrhythmias (Lown 3-4b, n = 18) than in the patients with stable rhythm. Platelet aggregation in the patients with acute myocardial infarction did not differ significantly from the controls and was not related to heart rhythm disturbances. The causal relationship of increased platelet adhesiveness to collagen and heart rhythm disturbances in acute myocardial infarction remains to be established. PMID- 8444498 TI - Control of pulmonary vasomotility in congestive heart failure. AB - Although enhanced sympathetic tone is a well-known component of the autonomic imbalance of heart failure, its influence on pulmonary vasomotility is undefined. We investigated the pulmonary circulation in 12 patients with congestive heart failure in NYHA functional class III and in a control group of 10 normal subjects. Sympathetic influence on pulmonary vessels was studied through adrenergic activation by the arithmetic test and the cold pressor test. A rubber balloon was distended in the inferior vena cava to reduce transpulmonary flow and its influence on vascular tone. In normal individuals the arithmetic test caused pulmonary vasodilation, probably because of the mechanical effect of a largely enhanced flow: in fact, caval obstruction unmasked a neurogenic vasoconstrictor response to the arithmetic test by simply reducing the amount of cardiac output increase. In patients with heart failure, cardiac output and pulmonary arteriolar resistance remained steady during the arithmetic test, no matter what the condition of the venous return was. The cold pressor test was always a vasoconstrictor stimulus, but only in normal subjects was vasoconstriction potentiated by reducing, with caval obstruction, transpulmonary flow and its vasodilatory influence. From these data an attenuation of the sympathetic influence on pulmonary vessels in congestive heart failure seems to be likely. This might be explained as the result of modifications of pulmonary vessels rather than of reduced sympathetic excitability since circulating catecholamine levels varied to similar extents in the two groups during the tests. In congestive heart failure interstitial edema and vascular wall imbibition might increase pulmonary vessel tone and decrease vascular receptor availability. Lower reactivity to sympathetic stimuli, particularly to the vasoconstrictor ones, would ensue. PMID- 8444499 TI - Early detection of coronary reperfusion by rapid assessment of plasma myoglobin. AB - We assayed plasma myoglobin and creatine kinase to elucidate the usefulness of rapid assessment of myoglobin for detecting coronary reperfusion in 31 patients with acute myocardial infarction. Reperfusion was achieved in 20 patients by thrombolytic therapy or angioplasty, and it was not in 11 patients. Blood sampling was performed before and 43 +/- 15 (+/- SD) min after the start of treatment. In the reperfused group, blood samples were obtained before and 26 +/- 10 min after reperfusion. Myoglobin was assayed by a new quantitative test based on latex agglutination turbidimetry which required an assay time of 10 min. After treatment, the rate of increase of plasma myoglobin was significantly higher than that of plasma creatine kinase in the reperfused group (9.7 +/- 9.5 and 2.8 +/- 1.6-fold), but not in the occluded group (1.8 +/- 0.6 and 1.5 +/- 0.3-fold). When a 3.0-fold or greater increase in myoglobin (1.9-fold or greater increase in creatine kinase) was taken as evidence of coronary reperfusion, the sensitivity and specificity were 95% and 100% (70% and 82% in creatine kinase), respectively. In conclusion, using the rate of increase of myoglobin, as measured by latex agglutination turbidimetry, coronary reperfusion can be diagnosed within 1 h after reperfusion. PMID- 8444500 TI - Prognostic significance of silent myocardial ischemia after a first uncomplicated myocardial infarction. AB - Forty asymptomatic patients were studied after a first uncomplicated myocardial infarction. They were 36 men and 4 women, with a mean age of 52.6 yr; the location of myocardial infarction was in the anterior wall in 18 (45%) patients and in the inferior wall in 22 (55%). The patients were submitted to: (1) 48-h Holter monitoring, during the 2nd and 8th weeks after the acute event; (2) exercise testing during the same periods; (3) cardiac catheterization and coronary arteriography. Patients with clinical conditions associated with cardiac rhythm disturbances or repolarization abnormalities were excluded. The electrocardiographic methods identified 11 (27.5%) patients with silent myocardial ischemia. Patients with and without silent ischemia were similar in relation to sex, age, coronary risk factors, arrhythmias, left ventricular function and follow-up. Patients with silent ischemia had more inferior wall myocardial infarctions, but the difference was not statistically significant. Patients with silent ischemia had significantly more extensive coronary artery disease (45.5% multivessel disease) when compared to those without ischemia (14.8% multivessel disease) (p < 0.05). After a 2-yr follow-up, 4 (36.4%) patients with and 1 (3.4%) without silent ischemia had a coronary event (p < 0.05). Kaplan-Meier analysis demonstrated a significantly higher cumulative probability of not experiencing a new coronary event for the patients without silent ischemia (96.5%) as compared to those with silent ischemia (62.3%) (p < 0.01). Our results suggest that silent myocardial ischemia after a first uncomplicated myocardial infarction carries an adverse prognosis and should be routinely investigated. PMID- 8444501 TI - Circulating alpha-actin protein in acute myocardial infarction. AB - We used Western-blot analysis to investigate the possible presence in the bloodstream of the contractile protein alpha-actin in 70 patients diagnosed with acute myocardial infarction on the basis of clinical, electrocardiographic and laboratory (creatine kinase and lactate dehydrogenase) criteria. Circulating protein was identified with a monoclonal antibody specific for cardiac alpha actin. Of the 70 control samples of blood, the immunoblot results were negative for alpha-actin in 98% of the cases. Of the 30 patients with skeletal muscle damage caused by surgery, 26 were negative for circulating alpha-actin. Of the 70 patients with acute myocardial infarction, circulating alpha-actin was found in 67 (95%) as a 43 kDa band in immunoblots; the highest circulating concentrations (0.0580 micrograms/microliters) were found in those with anterior acute myocardial infarction. Circulating alpha-actin was detected in samples taken between 1 and 180 h after the onset of pain, and showed a biphasic pattern of appearance. Our findings for serum alpha-actin, together with the relationship between serum concentrations of this protein and sex (p = 0.001), tobacco use (p = 0.007) and postepisode complications (p = 0.002), should make it possible to gain a deeper understanding of acute myocardial infarction as a clinical entity. PMID- 8444502 TI - Prothrombin fragment F1 + 2 concentrations for monitoring anticoagulation therapy with heparin. AB - We have compared the activated partial thromboplastin time with measurement of prothrombin fragment F1 + 2 concentrations (ELISA assay) during a 24-h period in a group of patients (n = 10) who had undergone elective coronary angioplasty and were anticoagulated post-procedure with heparin 1000 U/h. Four hours after the procedure all the patients were adequately anticoagulated according to activated partial thromboplastin time (median ratio 4.7:1) and the prothrombin fragment F1 + 2 concentration was significantly lower than pre-angioplasty values (0.5 vs 1.4 nmol/l, p = 0.04). At 24 h the median activated partial thromboplastin time ratio was still higher than the pre-procedure value (1.35 vs 0.9, p < 0.01), but the prothrombin fragment F1 + 2 concentration had risen to 2.1 nmol/l, with more variability in individual results within the patient group for the prothrombin fragment F1 + 2 concentration than for activated partial thromboplastin time (interquartile ranges (Q1, Q3) prothrombin fragment F1 + 2, 1.2-2.5; activated partial thromboplastin time, 1.2-1.5). The activated partial thromboplastin time is the standard method of monitoring the anticoagulant effect of heparin but may not fully reflect the functional coagulation status and accurately identify individual patients with less than adequate anticoagulation. Prothrombin fragment F1 + 2 concentrations may provide a more reliable indicator in individual patients of functional coagulation status in certain important situations where anticoagulation is critical such as following complicated coronary angioplasty. PMID- 8444503 TI - Post-exercise oxygen uptake kinetics in patients with left ventricular dysfunction. AB - We assessed the kinetics of oxygen uptake (VO2) after symptom-limited maximal exercise by use of cardiopulmonary exercise testing with a bicycle ergometer in normal subjects and patients with left ventricular dysfunction due to dilated cardiomyopathy. During the first few minutes after the cessation of exercise, the VO2-time relationship showed an exponential-like decrease. A monoexponential curve was fitted to this relationship of the first 3 min after exercise to obtain the time constant of the decrease in VO2 (T(VO2)). The results of exercise testing in 37 normal subjects (25 male and 12 female) revealed that T(VO2) was relatively independent of age and gender. Then, 30 male patients with dilated cardiomyopathy (10 in New York Heart Association functional class I, 12 in class II, and 8 in class III) were evaluated and the results were compared with those of 16 age-matched male control normal subjects. Although the amount of the estimated oxygen debt was smaller in the patient group, the time constant T(VO2) was 117 +/- 8 s for the controls as compared with 130 +/- 14 s for the patients in class I, 153 +/- 13 s for those in class II, and 219 +/- 49 s for those in class III. There were significant correlations between T(VO2) and anaerobic threshold (r = -0.68, p < 0.001), peak VO2 (r = -0.74, p < 0.001), and the increase in VO2 per work rate (r = -0.88, p < 0.001). T(VO2) also correlated with the ventilatory equivalent for carbon dioxide output (VE/VCO2) at peak exercise (r = 0.70, p < 0.001) and the time course of minute ventilation during the early phase of the post-exercise period (r = 0.67, p < 0.001). Thus, the time course of VO2 decrease after symptom-limited exercise is considered to be closely related to exercise capacity and also to the degree of exercise-induced hyperpnea in patients with left ventricular dysfunction. PMID- 8444504 TI - Biological risk factors for restenosis after percutaneous transluminal coronary angioplasty. AB - In an attempt to discern biological (such as thrombotic or fibrinolytic) risk factors in patients developing restenosis after percutaneous transluminal coronary angioplasty, the following factors were measured prior to angiography in a population of 23 patients (20 men, 3 women, mean age 57 +/- 5 yr) treated by a successful angioplasty (gain > 20% and residual stenosis < 50%) for stable angina pectoris and who had a routine angiographic restudy. The following factors were thus assessed: lipid factors: cholesterol, triglycerides, high density lipoprotein cholesterol, low density lipoprotein cholesterol, apolipoprotein AI, apolipoprotein B; coagulation factors: fibrinogen, antithrombin III, fibrinopeptide A, factor VIII coagulant, factor VIII antigen, protein C; factors of physiological fibrinolysis: plasminogen, alpha 2-antiplasmin, tissue plasminogen activator and euglobulin clot lysis time before and after venous occlusion, plasminogen activator inhibitor before venous occlusion; and factors of platelet release: beta-thromboglobulin, platelet factor 4. Also studied were clinical characteristics: age, gender, diabetes, hypertension, smoking habits, previous myocardial infarction; angiographic data: global extent of coronary artery disease, location of the stenosis in a bend or branch point, complexity of the lesion, initial and residual stenosis and treatment during follow-up. The coronary angiograms were analyzed by a computer-assisted method with automatic edge detection. On angiographic criteria, 6 patients (restenosis group) were judged to have developed a restenosis (30% decrease in diameter and/or return to a 50% stenosis). The other 17 patients (those without restenosis) were considered to have a persistent success. Apart from age (group without restenosis: 55 +/- 6; restenosis group 61 +/- 5, p < 0.04), there were no differences in clinical, angiographic or treatment variables. There were no differences in lipid factors, but significant differences were observed in hemostatic variables: fibrinogen (without restenosis: 3.18 +/- 0.83; restenosis: 3.83 +/- 0.51 milligrams, p = 0.05), tissue plasminogen activator before venous occlusion (without restenosis: 10.9 +/- 26.8; restenosis: 232.5 +/- 371.2 IU, p < 0.04), euglobulin clot lysis time after venous occlusion (without restenosis: 176.5 +/- 100.5; restenosis: 78.6 +/- 40.2 min, p < 0.05) and for marker of the platelet release: platelet factor 4 (without restenosis: 10.8 +/- 7.9; restenosis: 20.5 +/- 7.5 ng/l, p < 0.04). These findings indicate that patients developing restenosis after coronary angioplasty tend to have an imbalance in the prothrombotic-antithrombotic equilibrium prior to the procedure. PMID- 8444505 TI - Effect of ventriculotomy on postinfarction ventricular tachycardia in a canine model. AB - The antiarrhythmic efficacy of ventriculotomy without further resection or ablation was evaluated in 15 dogs with reliably inducible ventricular tachycardia after experimental myocardial infarction. The dogs were placed on cardiopulmonary bypass and assigned to one of two treatment groups: (1) cardiopulmonary bypass only (control) - 5 dogs, (2) ventriculotomy through the infarct scar - 10 dogs. The effects on induction of ventricular tachycardia were evaluated 2 and 4 weeks postoperatively and infarct histology was examined at the termination of the experiment. All of the control dogs maintained inducible ventricular tachycardia postoperatively. In contrast, ventriculotomy abolished arrhythmia induction in 6 of 10 dogs (p < 0.05). Ventriculotomy resulted in destruction of the surviving subepicardial myocardium overlying the infarct, which is a feature of arrhythmogenic areas in this model of postinfarction ventricular tachycardia. In conclusion, inducibility of ventricular tachycardia in this canine model of myocardial infarction is unaffected by thoracotomy and cardiopulmonary bypass, and is therefore well suited to investigation of surgical antiarrhythmic interventions. Ventriculotomy results in subepicardial scarring and is significantly antiarrhythmic. This effect should be taken into account when evaluating any adjunctive procedure in this model. PMID- 8444506 TI - Cross-sectional echocardiographic left ventricular geometry in rheumatic mitral stenosis. AB - The ultrastructural myopathic changes and deranged left ventricular contractile function have been reported in patients with rheumatic mitral stenosis. It is not clear if as a result of these myopathic changes, global left ventricular myocardial remodelling occurs to alter its normal elliptical shape in the absence of qualitative segmental asynchrony. To study the left ventricular cavity shape independent of chamber size, cross-sectional echocardiographically measured longest long axis (L) of the left ventricular cavity in the apical four-chamber view and short axis diameters at the level of tips of the mitral leaflets in the parasternal long axis view (D-1), of the basal cavity (D-2) and the apical segment (D-3) in the apical four-chamber view at end-diastole and their ratio, were studied in 20 patients with isolated rheumatic mitral stenosis. Twenty healthy volunteers matched for age, sex, heart rate, height and body surface area provided the normal control data. The patients with mitral stenosis had shorter long axis diameter (7.2 +/- 0.7 vs 7.9 +/- 0.5 cm, p < 0.001) and greater short axis/long axis diameter ratios at every level with the most pronounced change in the apical segment of the cavity (D-3/L 0.49 +/- 0.09 vs 0.40 +/- 0.05, p < 0.001). Left ventricular end-diastolic sphericity index was also markedly increased in the patients with mitral stenosis (0.57 +/- 0.09 vs 0.40 +/- 0.05, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444507 TI - Anomalous origin of the left coronary artery from the anterior aortic sinus: role of echocardiography. AB - Sudden death in the young is a dramatic event which can be avoided with a preventive identification of the underlying cause. We report one case in which we identify the anomalous origin of the left coronary artery from the right sinus of Valsalva by transthoracic and transesophageal echocardiography. PMID- 8444508 TI - Significance of exercise-induced ST-segment deviation in right-sided chest leads in the diagnosis of right ventricular ischemia. AB - Seventy-three patients were subjected to bicycle ergometry and exercise-induced ST-segment changes in right-sided chest leads were correlated with changes in conventional leads. ST-segment elevation in right-sided chest leads was found to be more frequent than ST-segment depression. ST-segment elevation in right-sided chest leads was commonly reciprocal to ST-segment depression in leads V3 to V7, indicating that this change is usually secondary to left ventricular subendocardial ischemia, rather than to right ventricular ischemia. ST-segment depression in right-sided chest leads was mostly a primary change indicating right ventricular subendocardial or posterior wall ischemia. It is, therefore, felt that ST-segment depression in right-sided chest leads is more sensitive and specific for right ventricular ischemia than ST-segment elevation in these leads. PMID- 8444509 TI - Congenital coronary arteriovenous fistula associated with atrioventricular valvular regurgitation in an octogenarian. AB - An arteriovenous fistula originating from halfway down the circumflex coronary artery, draining into the coronary sinus was first diagnosed in a patient of 81. For 10 years, she had had dyspnea on exertion, mild mitral regurgitation and permanent ventricular pacing for symptomatic bradyarrhythmia. She was treated medically and despite her age was offered transcatheter balloon embolization, but she refused to undergo such intervention. PMID- 8444510 TI - Pre-hospital cardiac arrest associated with coronary artery spasm. AB - A 37-yr-old woman with an 8-month history of chest pain, unrelated to exercise, was successfully resuscitated from out-of-hospital cardiac arrest due to ventricular fibrillation. Cardiac catheterisation revealed minor coronary artery disease. Ergometrine injection was associated with complete occlusion of the left anterior descending coronary associated with identical chest pain and pronounced ST-segment changes. PMID- 8444511 TI - Red blood cell deformability in diabetes mellitus: effect of phytomenadione. AB - Decreased deformability of red blood cells (RBC) in diabetes mellitus (DM) is considered to be linked to microcirculatory complications in this condition. As we found that phytomenadione increased RBC deformability in experimental animals, the question was raised, whether phytomenadione had the same effect on the RBC of diabetic patients. The study was performed in 10 patients with insulin-dependent diabetes mellitus, where the erythrocyte deformability was impaired. Patients received 10 mg/day phytomenadione i.m. for five days. Deformability was measured with policarbonate membranes (Nucleopore) with pore diameter 5 microns, under gravity. The results were expressed as the ratio (r) between the flow of 1.5 ml (r1) and 2 ml (r2) of RBC suspension and 1.5 ml of buffer. Phytomenadione increased the erythrocyte deformability in patients with diabetes mellitus, lowering the value r1 from 3.54 +/- 0.84 to 2.32 +/- 0.61 (p 0.02) and r2 from 7.80 +/- 2.41 to 4.65 +/- 1.07 (p 0.01). The values after treatment reached the range of healthy controls (r1 3.11 +/- 0.98, r2 6.52 +/- 3.04). The whole blood viscosity was significantly lowered after phytomenadione (5.28 +/- 0.58 mPas before, 4.64 +/- 0.74 mPas after, p < 0.02) with unchanged plasma viscosity, but significantly lowered internal viscosity of erythrocytes. PMID- 8444512 TI - A dynamical model for the separation of secondary resistance from tolerance to nitroglycerin infusion. AB - A dynamic model for the estimation of a residual hypotensive efficacy of nitroglycerin (NG) infusion was constructed to distinguish secondary resistance from tolerance to NG, as lost vs weakened efficiency. The model was tested by individual comparison in 82 of 92 patients with acute myocardial infarction or unstable angina. Ten patients were excluded from the study protocol due to complications that required therapy modification. NG infusion (20 micrograms/ml) efficiency was initially confirmed by a 10% decrease in the mean brachial artery (cuff) blood pressure. The infusion (63 hours mean duration) was discontinued every 12 hours for 30 minutes and pressure changes were analyzed. If NG hypotensive efficacy was maintained (as proved by at least 10% pressure increase), infusion was carried on using the initial dose. Lack of 10% pressure increase after 30-minute infusion discontinuity (tolerance) indicated the need for an increase in the NG dose until 10% pressure decrease (not below 105/60) was obtained. Lack of 10% pressure decrease, with a 5-fold increase in NG dose (up to 320 micrograms/ml), was considered to be a sign of secondary resistance. There were no proceeding complications and tolerance was found in 72 patients. Beside tolerance, secondary resistance was simultaneously present in 16 patients, while the NG efficacy was restored by dose increase in the remaining 78% of tolerant patients. "Paradoxical" pressure decrease was noted in 12 tolerant patients after the infusion interruption, while "paradoxical" pressure increase was observed in 3 resistant patients during the infusion acceleration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444513 TI - Acetylation of dapsone by human whole blood. AB - We studied the acetylation of dapsone (DDS) in vitro by whole blood taken from subjects with known acetylator phenotype. The acetylation of DDS by whole blood was both incubation time- and DDS concentration-dependent. Thus, it is highly recommended to separate plasma immediately after blood withdrawal during acetylation phenotyping using DDS. para-aminobenzoic acid (PABA) substantially inhibited the acetylation of DDS by whole blood taken from both slow and rapid acetylators, while procainamide (PAD) significantly inhibited DDS acetylation by whole blood taken from slow acetylators. At the highest PAD concentration used (208 microM), DDS acetylation by whole blood taken from rapid acetylators was also inhibited. In contrast, sulphanilamide (SAD) failed to produce any significant inhibition of the acetylation of DDS by whole blood taken from either slow or rapid acetylators. Furthermore, there was no correlation between DDS acetylation by whole blood in vitro and the acetylator status of the subject. It is therefore not possible to predict the acetylator phenotype by studying DDS acetylation by human whole blood. These results indicate that the DDS N acetyltransferase of human whole blood is most probably of the monomorphic type. PMID- 8444514 TI - Unchanged protein binding of penbutolol in renal insufficiency: a possible role of carbamylation. AB - The effect of in vitro carbamylation of serum protein with potassium cyanate on protein binding of penbutolol, a basic agent exclusively bound to alpha 1 acid glycoprotein (AAG), was investigated. Carbamylation of serum resulted in a weak increase on free fraction of penbutolol (4.45 +/- 0.54% before carbamylation vs 5.66 +/- 0.40% after; p < 0.025). Parallelly, potassium cyanate added to pure AAG and incubated for 90 min induced carbamylation of this protein (38 mumoles of 14C cyanate incorporated per gram of protein). A study in serum from patients with chronic renal disease (pre and postdialysis) showed no changes in protein binding of penbutolol, although AAG levels were significantly higher. However, Scatchard [1949] plot for penbutolol binding to serum from renal patients (both pre and postdialysis) showed a decrease in affinity constant (nKa = 11.13 x 10(5) M-1 in healthy volunteers, vs 5.56 x 10(5) M-1 in patients before dialysis and 4.57 x 10(5) M-1 after dialysis). We concluded that carbamylation of serum AAG in uremic patients could explain, in part, the absence of changes in protein binding of any basic drugs in this pathological condition. It appears that a decreased affinity constant could balance the effect of increased AAG levels. PMID- 8444515 TI - Xylitol-induced increase in purine degradation: a role of erythrocytes. AB - We administered xylitol intravenously to normal subjects to investigate the mechanism of xylitol-induced increase in the purine degradation in humans. Xylitol increased the plasma concentrations of hypoxanthine, xanthine and uric acid but decreased the blood concentration of pyruvic acid. The erythrocyte concentrations of IMP, AMP, ADP, glyceraldehyde 3-phosphate and fructose 1,6 diphosphate as well as the urinary excretion of hypoxanthine and xanthine were increased, while the erythrocyte concentration of ATP was decreased. In addition, the in vitro incubation studies using erythrocytes demonstrated that both xylitol induced purine degradation and xylitol-induced inhibition of the conversion of glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate were protected by pyruvic acid. These results indicate that xylitol-induced impairment of glycolysis in erythrocytes contributes to the observed xylitol-induced increase in the purine degradation in the body. PMID- 8444516 TI - Chemical and biological characterization of iron-protein succinylate (ITF 282). AB - ITF 282 is an iron succinyl casein complex containing 5% iron. The main property of the derivative is to keep iron bonded at acidic pH values. This accounts for a better tolerability of the compound compared with iron salts, during the treatment of iron deficiency. Pharmacological studies in normal and anemic rats demonstrated that this iron complex is almost as active as ferrous sulphate against iron deficiency anemia, but it is significantly less potent in increasing serum iron. Better gastrointestinal tolerability of ITF 282 was demonstrated in rats and dogs. Chemical and pharmacological properties of iron-protein succinylate are described. PMID- 8444517 TI - Pharmacokinetics and interactions of digoxin, theophylline and furosemide in diseases with edema. AB - In diseases with generalized edema caused by decompensated heart and liver diseases or kidney failure digitalis preparations, diuretics and theophylline -- if lung disease accompanies one of the above states -- are often used. Literature dealing with theophylline, digoxin and furosemide pharmacokinetics in edematous diseases was analyzed as well as theophylline or digoxin interactions with furosemide. The results obtained in these investigations are very dissimilar, even contradictory. In all the drugs investigated, it was found that serum drug concentration was reduced, that there were no changes in comparison with non edematous diseases and that drug concentrations were elevated in edematous diseases. Many problems in this field remain unsolved requiring further investigations of digoxin, theophylline and furosemide pharmacokinetics in liver, heart and kidney diseases accompanied by edema. As these drugs are often administered in these states, and having in mind their narrow therapeutic range (digoxin, theophylline), intoxication or a drug concentration decrease below the possibility of inducing any therapeutic effect are possible. PMID- 8444518 TI - AGPA and the village well. AB - This article is based on the author's presidential address, which was presented at the 50th anniversary meeting of the American Group Psychotherapy Association in February of 1992. Using the metaphor of the village well, Dr. Alonso argues that AGPA faces both the opportunity and challenge to serve as the leader in facilitating communication among four diverse groups: colleagues in other professional organizations; academia and its training programs; the world of managed care and third-party payers; and, the consumers of our services, our patients. PMID- 8444519 TI - Principles of leadership in brief training groups for mental health care professionals. AB - Leadership in brief training groups requires a high level of skill, energy, and professionalism. The group needs to be led in a purposeful, constructive manner. A metaphor for beneficial leadership is suggested through the image of a mountain guide who sustains and helps members of the group in their exploration of the psychological terrain that is themselves. The leader has five main tasks: (1) to contain the anxieties of the group, (2) quickly establish a therapeutic atmosphere in the group, (3) guide the group toward issues that can be addressed in the time available, (4) guard against damaging self-disclosure and loss of self-esteem, and (5) help the group end well. Clinical vignettes illustrate the realization of these practice points. PMID- 8444520 TI - Combining psychopharmacotherapy and group psychotherapy: problems and advantages. AB - This report presents the responses to the authors' survey of therapists' attitudes and perceptions regarding the problems and advantages of combining pharmacotherapy with group psychotherapy. Group therapists representing physicians, psychologists, and social workers were asked about their practices and attitudes regarding this practice. One hundred forty-three valid responses were received to the questionnaire (response rate = 55.4%). No significant differences among the three professions were found in years of experience, number of groups conducted, or percentage of included patients taking medication. The authors categorized the responses for both problems and advantages. The problem categories were medication arrangements and effects, impact on the group processes, relationship to the therapist, and interprofessional collaboration. The advantages were identical except for the initial category, which addressed group composition. The responses reflect clinicians' concerns, both positive and negative, and provide a framework for therapists to examine their practices. PMID- 8444521 TI - Process to recovery: in support of long-term groups for sexual abuse survivors. AB - This article presents a model for a long-term process group for treating adult survivors of childhood sexual abuse. The reasons for the preference of an ongoing group are presented in light of their relevance to the early traumas of survivors. The rationale and philosophy guiding these groups with their emphasis on strengths rather than pathology, on individuation, and on educational and therapeutic components are highlighted. The developmental life of the group and corresponding behavior of members at each stage are viewed within the overarching concept of closeness, a key issue for survivors to experience and work through during their recovery. PMID- 8444522 TI - Working with shame in the group treatment of male batterers. AB - The authors argue that shame is a core issue for many men who assault their partners. Shame must therefore be addressed in treatment groups. This article outlines how one intervention, "the confession," elicits shame and how that shame is negotiated through the various stages of group development. PMID- 8444523 TI - A Persian Gulf War support group: process, viability, and flexibility. AB - Observations of a Persian Gulf War support group suggest that the support group is a viable approach to ameliorating the stress of war among those personally affected. Cohesiveness developed readily, and facilitated a social support network. Therapeutic factors are compared with previous support group literature, and existential issues appear to be involved in groups addressing an uncontrollable stressor and/or the possibility of death. The volatility of the stressor produced variations in group character (supportive psychotherapy versus support versus self-help), necessitating a flexible leadership role. Observations are offered toward clarifying the nature of support groups in general. PMID- 8444524 TI - The role of evaluation in clinical practice: overview and group treatment illustration. AB - A variety of intrinsic and extrinsic factors exert pressure on clinicians and researchers to forge a more effective alliance in their mutual efforts to understand treatment process and outcome. The authors provide a general framework and a specific group-therapy model to demonstrate how research measures can facilitate this integration and thereby improve the quality of service delivery. We divide treatment into four phases: negotiation, retention, enhancement, and evaluation, and illustrate how psychotherapists can use research instruments to overcome problems at each stage of intervention. PMID- 8444525 TI - Immunofluorescence in dermatology. PMID- 8444526 TI - Pharmacology of psychotropic drugs useful in dermatologic practice. PMID- 8444527 TI - Genital ulcer disease. PMID- 8444528 TI - Trichotillomania: a manipulative alopecia? PMID- 8444529 TI - Cutaneous myiasis caused by larvae of Cordylobia anthropophaga (Blanchard). AB - BACKGROUND: Cordylobia anthropophaga (Blanchard) is a nonhematophagous dipteron belonging to the Calliphoridae family. It produces a myiasis called "tumbu fly" or "ver de Cayor" or "mango fly" or "skin maggot fly". CASE REPORTS: We describe two women, 24 and 23 years of age, affected by cutaneous myiasis caused by the larva of Cordylobia anthropophaga. In both cases the myiasis was contracted in Senegal and was characterized by a single lesion localized to the flank and the thigh respectively. From each of these lesions a single larva was extracted. DISCUSSION: This myiasis represents a typical example of tropical disease that in the past was unknown to Western dermatologists. PMID- 8444530 TI - Suicidal ideation in psoriasis. AB - BACKGROUND: Psoriasis has been associated with depressive disease and case reports of completed suicide. METHODS: 217 consenting psoriasis patients completed the Carroll Rating Scale for Depression (CRSD), a 52-item self-rated scale, with four of the items directly addressing wishes to be dead and suicidal ideation. The patients also self-rated the severity of their psoriasis. RESULTS: 9.7% of patients reported a wish to be dead, and 5.5% reported active suicidal ideation at the time of the study. The death wish and suicidal ideation were associated with higher depression scores (P < 0.0001) and higher patient self ratings of psoriasis severity (P < 0.05). Patient self-reports of psoriasis severity correlated directly with the overall depression scores (r = 0.39), P < 0.0001). CONCLUSIONS: The comorbidity between depressive symptoms, suicidal ideation, and psoriasis severity is in contrast with reports that severe depression and suicidal ideation are mainly a feature of life-threatening medical disorders such as malignancies. Our finding may have important implications in the management of psoriasis. PMID- 8444531 TI - Lepromin responses in recipients of a candidate antileprosy bacterin vaccine (WHO IMMLEP Mycobacterium leprae killed preparation) in the USA. AB - BACKGROUND: Identification of the nine-banded armadillo as a potential source of massive numbers of Mycobacterium leprae led to the development of a candidate bacterin vaccine for possible immunoprophylaxis. METHODS: Volunteers were from a leprosy-hypoendemic, nonBCG-using area (USA). They had been vaccinated intradermally 3 years earlier with a candidate antileprosy bacterin vaccine of irradiated and autoclaved Mycobacterium leprae obtained from experimental nine banded armadillos. They were tested for dermal responsiveness to standard lepromin A. RESULTS: Values for induration and erythema appeared slightly greater for the vaccinated group; however, the differences were not statistically significant, indicating no appreciable 'anamnestic' effect on either Fernandez (early) or Mitsuda (late) reactions after 3 years. CONCLUSIONS: Because previous studies had demonstrated that administration of this bacterin produced no humoral changes, it now appears less probable that laboratory methods will be of much help in assessing even possible effectiveness of such vaccination. PMID- 8444532 TI - Leprosy in children: a prospective study. AB - BACKGROUND: Leprosy has been identified as an important health problem in the pediatric age group. The study of leprosy in children is imperative as it may unravel the missing links in the natural evolution of the disease and dispel the uncertainty of the precise incubation period. METHODS: The study was undertaken on patients attending the Urban Leprosy Centre. There were 161 children in the age group of 0 to 14 years, amongst 3184 cases of leprosy, detected between 1981 and 1991. The diagnosis in each was formed after meticulously recording the clinical features, slit-skin smear examination, and histopathologic characteristics. In addition, a detailed history of duration of the disease was elicited by complement recall method. RESULTS: The study revealed an incidence of 5.06% amongst leprosy patients, in an urban setting. The boys:girls ratio was 2.6:1. The mean duration of the disease was 1.2 years in paucibacillary and 2.8 years in multibacillary. History of intra- or extrafamilial contact was elicited in 8.7%. The typical lesion was a "hypopigmented macule," either of indeterminate, tuberculoid, borderline tuberculoid, or borderline borderline leprosy. Borderline lepromatous, lepromatous, and polyneuritic leprosy were uncommon. CONCLUSIONS: Leprosy in children is a well-established distinct entity. Any hypopigmented macule in pediatric age group should arouse suspicion of leprosy. The diagnosis is clinical. Other investigative parameters, namely slit skin smear, and histopathology may supplement but not supplant the diagnosis. PMID- 8444533 TI - Plica neuropathica after using herbal soap. PMID- 8444534 TI - Eruptive syringoma in a Chinese boy. PMID- 8444535 TI - American cutaneous leishmaniasis: intermediate form. PMID- 8444536 TI - Effectiveness of a dapsone compliance program in leprosy. AB - BACKGROUND: Long-term effectiveness of a dapsone compliance program was assessed in patients with leprosy. METHODS: The monitoring program consists of urine dapsone/creatinine ratio determination at each visit with subsequent patient feedback and education. Eighty-eight patients receiving dapsone and seen in a leprosy clinic from 1985-1990 were included. RESULTS: The proportion of patients compliant with dapsone during a given year ranged from 70.0% (1987) to 94.4% (1989). Overall compliance for the 6-year period was 81.6%. This level of compliance was significantly different (P < 0.05) than the baseline compliance in the leprosy clinic of 46.7%. CONCLUSIONS: Compliance monitoring, combined with active patient involvement, was effective in sustaining high compliance over a 6 year period. PMID- 8444537 TI - Comparison of topical phenytoin with normal saline in the treatment of chronic trophic ulcers in leprosy. AB - BACKGROUND: Trophic ulceration, one of the most common complications of leprosy, is disabling, distressing, and demoralizing for the patient. METHODS: The wound healing effects of topical phenytoin powder were compared with those of normal saline in a controlled in-patient study of 100 patients with 110 trophic leprosy ulcers of varying chronicity, over a 4-week study period. Fifty patients were assigned to the topical phenytoin group and 50 to saline therapy group. Ten patients had two ulcers each, and, in these cases, one ulcer was treated with phenytoin and the other with saline. RESULTS: Over the 4-week treatment period healthy granulation tissue appeared earlier, and mean percentage of ulcer volume reduction was greater, in the phenytoin group (72.1 +/- 19.9% versus 55.5 +/- 21.6%) compared with the control group. CONCLUSIONS: This difference was statistically significant at the level of P < 0.001. Phenytoin appears to be a useful agent for the promotion of healing of trophic leprosy ulcers. PMID- 8444538 TI - Topical phenytoin in wound healing. AB - BACKGROUND: Phenytoin, introduced in 1937 as an antiseizure medication, has since been reported to promote wound healing when applied as a topical agent. This study was undertaken to evaluate its effectiveness in chronic skin ulcers. METHODS: Seventy-five inpatients with chronic skin ulcers were included in this controlled trial. Forty patients were treated with topical phenytoin, and 35 patients with conventional saline dressings. Assessment of the wounds included wound area, bacteriologic cultures, and clinical assessment by blind observers at baseline and every 7 days thereafter over the 4-week treatment period. RESULTS: Wound area reduction was greater in the phenytoin group than in controls. Fifty percent of phenytoin-treated wounds had negative cultures by day 7, compared to 17% of controls. Healthy granulation tissue appeared earlier with phenytoin. At the end of the fourth week, 29 of 40 phenytoin-treated ulcers had healed completely versus 10 of 35 controls. CONCLUSIONS: Topical phenytoin appears to be an effective, inexpensive, and widely available therapeutic agent in wound healing. Further clinical use and evaluation is merited. PMID- 8444539 TI - Amoxicillin and clavulanic acid in the treatment of actinomycetoma. AB - BACKGROUND: Mycetoma is a relatively frequent disease in tropical countries. Drugs commonly used need a long period of treatment, and some cases are resistant to these drugs, especially those with bone or visceral involvement. The combination of amoxicillin-clavulanic acid has shown effectiveness against strains of Nocardia brasiliensis in vitro. METHODS: We have used this combination in two cases of mycetoma caused by N. brasiliensis, both with bone involvement and resistance to the drugs usually used. A dose of three tablets a day for 5 to 6 months was given (each tablet contains 500 mg of amoxicillin and 125 mg of clavulanic acid). RESULTS: Clinical and mycologic amelioration was observed in the two cases after completing the treatment. There were no side effects or relapses after 3 to 6 months of follow-up after treatment. CONCLUSIONS: We propose this antibiotic as a new option for the treatment of some special cases of actinomycetoma with bone or visceral involvement or resistance to the drugs commonly used in this disease. PMID- 8444540 TI - History of Russian dermatology. PMID- 8444542 TI - Skin manifestations observed in HIV-infected persons. PMID- 8444541 TI - Acquired hypertrichosis lanuginosa and polymyositis. PMID- 8444543 TI - Hearing loss in very preterm and very low birthweight infants at the age of 5 years in a nationwide cohort. AB - In a geographically defined population of very preterm and very low birthweight infants (gestational age < 32 weeks and/or birthweight < 1500 g) hearing was evaluated in 890 children by pure-tone audiometry at the age of 5 years. Hearing loss was conductive/unspecified in 123 (13.8%) and sensorineural in 13 (1.5%) children. The prevalence of sensorineural hearing loss was 15 times as high as in 5-7 year old children in the Dutch population at large. The sensorineural hearing loss prevalence in very low birthweight and extremely low birthweight infants was similar. On account of communication disorders 10 (1.1%) children were classified as disabled and 6 (0.7%) as handicapped, following the definitions of the International Classification of Impairments, Disabilities, and Handicaps of the World Health Organisation. Children with conductive hearing loss had a higher risk of impairments, disabilities and handicaps of language and speech development, than children with normal hearing, the difference being statistically significant. The same holds for children with sensorineural hearing loss; moreover they had a significantly higher risk of impairments, disabilities and handicaps of mental development. Overall comparison of children with and without sensorineural hearing loss proved that the children with sensorineural hearing loss had a significantly less favourable outcome, based on 15 perinatal factors simultaneously. The age at which sensorineural hearing loss in very preterm and/or very low birthweight infants is detected has to be improved. PMID- 8444545 TI - Evoked otoacoustic emissions in preterm infants. AB - Since Kemp's discovery of the otoacoustic emissions phenomenon [7], much study has been given to understanding the nature of it and its ontogeny. Development of the evoked otoacoustic emissions (EOAE) has spurred much interest because they may used as a valid and relatively quick test to assess cochlear integrity in the very youngest patients. One thing that has been learned is that EOAE amplitudes are much larger in normal ears of infants than in normal ears of adults. We asked about the form of this development in a longitudinal, rather than cross sectional, study in an investigation on children born before 40 weeks postconceptional age. We were able to examine reliably five ears of four preterm babies while they remained in the neonatal intensive care unit. The EOAEs of these ears were then studied to determine whether and how they changed over time. To do this, we examined both their amplitudes and their spectral properties. It turned out that there are properties of the EOAE spectrum that may be related to post-conceptional age. These are described herein. These findings are expected to have considerable clinical utility as more and more researchers are able to confirm their validity. PMID- 8444544 TI - Protracted secretory otitis media. The impact of familial factors and day-care center attendance. AB - This study's objective was to assess the impact of familial factors, day-care center attendance, and passive smoking on the incidence of protracted secretory otitis media (SOM). An unselected cohort of 1306 Swedish children were followed from birth to 7 years of age. Information about physician visits and insertions of tympanostomy tubes for SOM was collected at the ENT-departments in one Swedish county. The material was analyzed by life table methods and Cox's regression analysis. At the ages of 3, 5 and 7 years, 1%, 4% and 6%, respectively, of the children had been treated by tympanostomy tubes for SOM. The cumulative incidence of protracted SOM was four times higher among the children who had a sibling with the same health problem. Attendance at a day-care center of 12 or more months during the first 4 years of life increased the risk for protracted SOM by 2.6 times. No association was found between parents' smoking habits and the incidence of protracted SOM. PMID- 8444546 TI - Complications of rigid laryngo-bronchoscopy in children. AB - Twenty-five complications (of which 2 were lethal) occurred in 1332 rigid laryngo bronchoscopies performed under general anesthesia in the Sophia Children's Hospital during an 8 year period (1982-1990). The nature and circumstances of these complications were studied retrospectively. Important intraoperative complications were hemorrhage and cardiac arrhythmia; postoperative complications were intoxication and respiratory complications. Three risk factors: tetralogy of Fallot, biopsy/drainage, and extraction of an aspirated foreign body appeared to be significantly associated with complications. The results of this study were compared with those reported in studies of rigid and flexible laryngo bronchoscopies in children. PMID- 8444547 TI - Early postnatal treatment of congenital facial palsy in patients with hemifacial microsomia. AB - Facial palsy associated with hemifacial microsomia results in a devastating deformity. To date, no attempts on early treatment of the associated facial palsy have been reported. A therapeutic approach may be to provide reinnervation to the affected muscles through a crossed facial nerve graft. The purpose of this paper is to present 8 cases of hemifacial microsomia with associated facial palsy. All these patients were treated before 1 year of age with cross-sural-to-facial nerve grafts. After a 1 year follow-up, clinical and electrodiagnostic results indicate axonal continuity through the graft and evidence of reinnervation activity in all patients. Crossed facial nerve grafting appears to be an adequate procedure in patients with hemifacial microsomia with associated facial palsy. PMID- 8444548 TI - Ascariasis and acute otitis media. AB - Ascaris lumbricoides has rarely been implicated in the causation of middle ear disease. An infant who developed acute suppurative otitis media while on antibiotics for an upper respiratory tract infection and who extruded an ascaris worm from the ear is presented. The otitis media subsequently resolved. Our understanding of the pathophysiology of ascariasis in the eustachian tube and middle ear is discussed. PMID- 8444549 TI - Sinus complications in mucopolysaccharidosis IH/S (Hurler-Scheie syndrome). AB - Hurler-Scheie syndrome is a genetic compound of two mucopolysaccharidoses, the Hurler and Scheie syndromes. The genetic error of metabolism caused by this syndrome produces intermediary systemic effects in the affected individuals. Lacking the enzyme alpha-L-iduronidase, glycosaminoglycans are deposited in the tissues, causing multiple systemic effects and creating many problems for the otolaryngologist. Although early bone marrow transplantation is currently being performed to prevent or reverse many of the systemic manifestations of this disorder, there remains a large population of children past the age at which bone marrow transplantation can be effective. Sinus complications have not previously been reported in the mucopolysaccharidoses and may be more frequently recognized as these patients' longevity increases. We present a patient with Hurler-Scheie syndrome who developed severe nasal polyposis requiring sinus endoscopic removal. PMID- 8444550 TI - Squamous cell carcinoma of the tongue occurring as a subsequent malignancy in a 12-year-old acute leukemia survivor. AB - Squamous cell carcinoma of the tongue is rare in children and previously unreported as a second malignancy after survival of acute leukemia. Usual etiologic associations such as smoking and alcohol use are not commonly seen in this population, and exposure to immunosuppressive and antineoplastic agents including radiation therapy may contribute to the occurrence of these tumors. A review of the literature reveals only 21 previously reported cases of squamous cell carcinoma of the tongue in children less than 15 years old, and in only two cases was it a second malignancy; none were in leukemia survivors. Small numbers prevent accurate conclusions with regard to tumor behavior, but prognosis appears to be poor with aggressive invasion and early metastasis common. Follow-up of survivors of leukemia and its therapy with immunosuppressive and cytotoxic drugs and radiation should include regular careful head and neck examinations. PMID- 8444551 TI - The open surgical approach to subglottic hemangioma. PMID- 8444552 TI - Epidemiology of chronic suppurative otitis media in Saudi children. AB - An epidemiological survey was carried out in Riyadh to establish the prevalence of chronic suppurative otitis media in Saudi children. 6421 children aged 2 months to 12 years were examined clinically, their ears were inspected by otoscopic examination by an ENT specialist, and the evaluation of hearing was undertaken by an audiologist using a memory screening audiometer (Madson 84-11). Ninety-four children (1.5%) had chronic ear disease being of the following types: congenital cholesteatoma (n = 1), acquired cholesteatoma and posterosuperior retraction (n = 5), and central perforation (n = 88), 16 of which had active ear discharge. These results were compared with other results in developed and developing countries. The factors predisposing to or associated with chronic ear disease such as environmental, genetic, congenital ear anomalies and cleft palate have been discussed. PMID- 8444553 TI - Hearing loss and vestibular dysfunction in childhood from the use of streptomycin in Albania. AB - With the entry of a large number of Albanians in the area of Epirus over the past 8 months, a significant number of children with hearing problems or deafness has been examined in the out patient ward of the University Hospital of Ioannina. From the Pediatric-Neurologic-Psychiatric and Otorhinolaryngologic examination of these children, 18 cases with hearing problems and vestibular dysfunction due to administration of streptomycin sulfate have been defined. This article reports the ototoxic drug which has been used and is still being used in Albania, the procedure of audiological and vestibular investigation, and the damage which has been evoked in the auditory and vestibular pathway of the children in whom it has been administered. PMID- 8444554 TI - Chronic otitis media and early speech development: a case study. AB - A case study of the speech development in a male infant with chronic otitis media is reported. The phonetic behavior characterizing the child's vocalizations was sampled monthly between the ages of 11 and 21 months, as he progressed from pre speech to early speech periods of language development. Results of monthly phonetic inventory analyses indicated age-appropriate types of consonants in his pre-word and later-word vocalizations. However, the child's repertoire of consonants was considerably reduced as he first began to produce meaningful speech. Results of phonetic diversity analyses revealed an overall lack of phonetic complexity in his vocalizations throughout the course of study. In general, the child's early sound productions were characteristic of developmental delay, closely resembling the speech patterns found among severely hearing imparied children. Findings are discussed with respect to the probable influence of chronic otitis media with effusion on a child's eventual speech development. PMID- 8444555 TI - Hearing and language in preschool very low birthweight children. AB - To get more insight into preschool language and hearing in high-risk very low birthweight (VLBW) children, we conducted a prospective study in a cohort of 79 children. The prevalence of language impairment and hearing loss at age 3-4 years, their relationship to each other as well as to perinatal conditions, neurodevelopmental outcome and the home environment are described. Mild hearing loss was found in 26%, moderate hearing loss in 13% and severe hearing loss in 3% of the children. None of the children was deaf. Abnormal tympanometry was found in 57% of the children. Hearing loss at age 4 years was related to a less optimal neonatal condition and was not related to the obstetrical condition or to neonatal cerebral ultrasound findings. Language impairment was found in 21% of the children at age 3.6 years. Receptive and expressive language was not related to perinatal conditions. There was no relation between the language assessments and the audiological assessments. Cognition and the home environment of the child were the only independent variables in the prediction of language in preschool VLBW children. PMID- 8444556 TI - The membranous tonsillitis during infectious mononucleosis is nevertheless of bacterial origin. AB - Samples from the fur covering the palatine tonsils of 10 patients with infectious mononucleosis (IM) were subjected to fluorescence microscopy after staining with acridine orange. Standard aerobic cultures from swabs were set up simultaneously. The fur constituted a mass of variously sized cocci and rods intermingled with granulocytes and cellular detritus. Five patients had growth of beta-haemolytic Streptococci on the tonsils. Bacteria in abundance were found attached to the tonsillar epithelial cells. The B-lymphotrophic Epstein-Barr virus, responsible for the IM infection, causes an immense increase in the bacterial colonization of the tonsillar surfaces, probably due to an increased attachment of bacteria to the tonsillar epithelial cells. PMID- 8444557 TI - Impalement injuries of the palate in children: review of 131 cases. AB - Impalement injuries of the soft palate and oropharynx are common injuries especially in children. Devastating neurologic sequelae secondary to thrombus propagation in the internal carotid artery are rare but well-documented complications of these innocuous appearing injuries. Neurologic sequelae have been reported anywhere from 3 to 60 hours after the injury. Protocols that include hospitalization up to 72 hours have been advocated. In order to evaluate the effectiveness and practicality of such protocols, all hospital admissions for palate injuries in the past 17 years were reviewed. Of the 131 cases reviewed, no complications were discovered during hospitalization, nor were there any complications in these patients seen in follow up. Based on this review, the majority of soft plate and oropharyngeal impalement injuries can be managed on an outpatient basis. Parental counseling, similar to instructions given in instances of mild head trauma, as well as close follow up in the office are felt to be a more reasonable and as well as a safe treatment plan. A suggested instruction form is presented. PMID- 8444558 TI - Successful nasoendoscopic and aerodynamic examinations of children with speech/voice disorders. AB - An 8-year retrospective analysis of aerodynamic and nasoendoscopic examinations of children with a variety of speech and voice disorders shows that these examinations can be completed with a high rate of success. Moreover, the examinations were achieved with relative ease in children as young as 2 years old. Several clinicians were involved in the examinations, illustrating the viability of the methods. It is suspected that the failures to complete the examinations relate more to the examiners' methods and skills than to the child's tolerance of the instrumentation. PMID- 8444560 TI - An endodermal sinus tumor of the head and neck region. AB - A 2-year-old patient with a recurrent endodermal sinus tumor of the nasopharynx is presented. After the first attempt to surgically excise the tumor it recurred, causing upper airway obstruction within 2 months. Combined treatment with surgery, radiotherapy and chemotherapy resulted in a disease-free survival of four years. PMID- 8444559 TI - Fibrous hamartoma of infancy presenting as a perspiring neck mass. AB - An unusual case of fibrous hamartoma of infancy is reported. This lesion presented as a gradually enlarging, perspiring left neck mass in an eight month old male. Histologic examination revealed the characteristic features of this entity, with the additional finding of eccrine gland hyperplasia. In a review of the literature, we found no other reports of this unique histologic finding or clinical presentation. PMID- 8444561 TI - Spontaneous tonsillar bleeding; secondary to acute tonsillitis in children. AB - Serious spontaneous tonsillar bleeding in three children was considered with respect to cause(s) and therapy. In two of the children the cause was related to streptococcal infection, and to hemophilus in the third child. A clinical and laboratory follow-up on our diagnosis indicated an infectious cause in each instance, inducing superficial vascular wall erosion. In our clinic the incidence of this relatively rare medical phenomenon in 254 cases of acute tonsillitis, has been only 1.2%. The children were successfully treated with conservative local treatment, such as cauterization and systemic antibiotics. PMID- 8444562 TI - Lymphangioma presenting as congenital stridor. PMID- 8444563 TI - Juvenile respiratory papillomatosis: acyclovir reassessed. AB - Four patients with aggressive respiratory papillomatosis have been treated with oral Acyclovir as adjuvant therapy while continuing to undergo regular endoscopy and laser treatment to the lesions. The duration of Acyclovir administration ranged from 2 weeks to 3 months. Two patients had papillomatosis confined to the larynx and two in addition had disease in the lower respiratory tract. One of the four patients had less aggressive disease during the treatment period. Acyclovir does not appear to significantly influence respiratory papillomatosis. Acyclovir's activity is dependent upon the presence of virally encoded thymidine kinase. This enzyme is not known to be encoded by papilloma viruses. Acyclovir is not recommended in the treatment of juvenile respiratory papillomatosis. PMID- 8444564 TI - Respiratory distress associated with bilateral nasolacrimal duct cysts. AB - Nasolacrimal duct system cysts with intranasal extension is a rarely reported cause of respiratory distress in the newborn. Nine often previously reported patients have demonstrated a paranasal mass on examination. Most of these patients have been female and most have required surgical intervention to relieve the obstruction. We present a case of a male newborn with bilateral NLDS cysts with intranasal extension causing respiratory distress, and no evidence of paranasal mass on examination. Nasal endoscopy is essential in the work-up of all patients with nasal obstruction and respiratory distress. The MRI scan was used in the diagnostic work-up to further evaluate the condition. The NLDS cysts with nasal extension resolved spontaneously. PMID- 8444565 TI - Phosphorus magnetic resonance spectroscopy of the calf muscle in patients with peripheral arterial occlusive disease. AB - RATIONALE AND OBJECTIVES: To investigate the potential of 31P magnetic resonance spectroscopy (MRS) in the management of severe peripheral ischemic disease, phosphocreatine:inorganic phosphate (PCr:Pi) and PCr:adenosine triphosphate (PCr:ATP) ratios were compared with a clinical ranking of arterial insufficiency. METHODS: 31P MR spectra of the muscles in the lower and upper leg were measured in a group of healthy volunteers (n = 21) and in a group of patients (n = 42) with arterial occlusive disease. The patients were graded according to the categories advised by the Ad Hoc Committee on Reporting Standards (AHCRS). Spectra were obtained 12 and 20 cm below and 15 cm above the knee joint. RESULTS: The PCr:Pi ratio showed a significant decrease between measurements 12 and 20 cm below the knee joint for patients with severe arterial insufficiency (AHCRS 4-6), whereas this decrease was not found in patients with mild or moderate arterial insufficiency (AHCRS 1-3). CONCLUSIONS: Although the observed spatial variation in PCr:Pi ratio measured at rest does not offer profound insight into muscle physiology, the authors' results suggest that MRS may be useful in assessing the severity of peripheral vascular disease. PMID- 8444566 TI - Magnetic resonance imaging of blood flow with a phase subtraction technique. In vitro and in vivo validation. AB - RATIONALE AND OBJECTIVES: One promising approach to flow quantification uses the velocity-dependent phase change of moving protons. A velocity-encoding phase subtraction technique was used to measure the velocity and flow rate of fluid flow in a phantom and blood flow in volunteers. METHODS: In a model, the authors measured constant flow velocities from 0.1 to 270.0 cm/second with an accuracy (95% confidence intervals) of +/- 12.5 cm/second. There was a linear relationship between the magnetic resonance imaging (MRI) measurement and the actual value (r2 = .99; P = .0001). RESULTS: Measuring mean pulsatile flow from 125 to 1,900 mL/minute, the accuracy of the MRI pulsatile flow measurements (95% confidence intervals) was +/- 70 mL/minute. There was a linear relationship between the MRI pulsatile flow measurement and the actual value (r2 = .99; P = .0001). In 10 normal volunteers, the authors tested the technique in vivo, quantitating flow rates in the pulmonary artery and the aorta. The average difference between the two measurements was 5%. In vivo carotid flow waveforms obtained with MRI agreed well with the shape of corresponding ultrasound Doppler waveforms. CONCLUSIONS: Velocity-encoding phase subtraction MRI bears potential clinical use for the evaluation of blood flow. Potential applications would be in the determination of arterial blood flow to parenchymal organs, the detection and quantification of intra- and extra-cardiac shunts, and the rapid determination of cardiac output and stroke volume. PMID- 8444567 TI - Analysis of skull anthropometric measurements in patients with neurofibromatosis type-1. AB - RATIONALE AND OBJECTIVES: The authors studied selected anthropometric measurements of plain postero-anterior and lateral skull roentgenograms to ascertain whether these were useful in distinguishing patients with clinically probable neurofibromatosis type-1 from controls. METHODS: A retrospective review of medical records of patients for whom skull roentgenograms were available was conducted. Patients were assigned to one of three groups: definite neurofibromatosis type-1 (DNF), probable neurofibromatosis type-1 (PNF), and controls. A blinded analysis of 29 measurements, 9 qualitative assessments, and 3 area/volume calculations was performed. RESULTS: There were 58 patients (29 controls, 14 DNF, and 15 PNF). The majority (75%) of all predetermined landmarks could be ascertained in 43 of these subjects. After age and gender were held constant, analysis of covariance showed that both DNF and PNF subjects could be distinguished from controls, but not from each other when comparing the mean: sella turcica height (P < .001), sella turcica depth (P < .005), skull width (P < .001), skull length (P < .002), skull height (P < .003), and skull volume (P < .0001). CONCLUSIONS: Anthropometric analysis of skull roentgenograms coupled with results of clinical examination improves the ability to distinguish between patients with DNF and PNF from controls. PMID- 8444568 TI - Percutaneous treatment of abdominal hydatid cysts with hypertonic saline and alcohol. An experimental study in sheep. AB - RATIONALE AND OBJECTIVES: Seven naturally infected sheep with proper hepatic and peritoneal hydatid cysts were studied to assess a new percutaneous approach for cystic hydatid disease. METHODS: A needle was inserted into the cyst cavity of sheep under sonographic guidance. Immediately after instillation of hypertonic saline to inactivate protoscolices, ultrasound demonstrated that germinal and laminated membranes of the hydatid cysts were separated completely from the pericyst in all sheep. Later, a catheter was inserted into the cyst cavity using Seldinger technique. Alcohol was used as a sclerosing agent. RESULTS: Ultrasound showed reduction in cyst size and progressive solidification. No anaphylactic reaction was observed. After sonographic follow-up that lasted from 1 to 26 weeks, the sheep were killed to evaluate macroscopic and histologic changes. At autopsy, no secondary cyst formation was seen. The appearance of treated cysts was different from the others, and there were signs of involution. The histologic sections did not show any viable protoscolices or daughter cysts. The authors observed pericyst hyalinization, inflammatory cells in the cyst wall, cyst wall necrosis, calcification of cyst wall, degeneration of laminated membrane, severe degeneration or absence of germinal membrane, and inflammatory cells and necrotic material in the cyst cavity. CONCLUSIONS: Percutaneous treatment of hydatid disease was effective in the animal model. Ultrasound was useful in evaluating the intervention. PMID- 8444569 TI - Urine profiles and kidney histologic findings after intravenous injection of mannitol and iohexol in the degeneration phase of gentamicin nephropathy in rats. AB - RATIONALE AND OBJECTIVES: Previous studies have shown that iodinated contrast media may cause further renal dysfunction in tubulointerstitial nephropathy induced by gentamicin. The current investigation was undertaken to study whether the dysfunction after intravenous injection of a low-osmolar contrast medium is due to a chemotoxic and/or an osmotic effect. METHODS: Urine profiles were followed for 3 or 9 days after intravenous injection of saline, mannitol, and varying dosages of iohexol (1, 2.5, 5, and 10 mL/kg body weight (BW); 350 mg I/mL) in 60 rats, in which intramuscular injection of 40 mg/kg BW gentamicin had been administered daily nine times. A seventh group of 10 rats was given 20 mg/kg BW gentamicin and 5 mL/kg BW of 350 mg I/mL iohexol. Another 10 rats injected with saline served as controls. RESULTS: Both mannitol and iohexol increased the excretion of albumin and the enzyme N-acetyl-B-D-glucosaminidase (NAG) temporarily; the effect was independent of the dose of iohexol. There was a dose dependent effect on the transient increase in excretion of the enzymes lactate dehydrogenase (LDH), gamma glutamyltransferase (GGT), and alkaline phosphatase (ALK); mannitol did not increase the excretion of these enzymes. In the group given 20 mg/kg BW gentamicin, only the dose-dependent effects of iohexol were seen. Neither various plasma components nor light/electron microscopy showed any changes that could solely be related to the contrast medium. CONCLUSIONS: Iohexol produces transient renal effects in gentamicin nephropathy, which may be due to both chemotoxic and osmotic mechanisms. PMID- 8444570 TI - Multiplanar reconstruction in magnetic resonance evaluation of the knee. Comparison with film magnetic resonance interpretation. AB - RATIONALE AND OBJECTIVES: At many institutions, three-dimensional magnetic resonance imaging (MRI) is routinely used for examination of the knee. Multiplanar reconstruction (MPR) is a method of displaying three-dimensional datasets. The authors assessed the usefulness of MPR for evaluating knee MRI datasets by comparing readers' performance using MPR and conventional film MRIs. METHODS: Eight patients with internal derangement of the knee were studied. All had MRI datasets acquired in the sagittal plane using a three-dimensional gradient-echo fast imaging with steady-state precession (FISP) sequence. Arthroscopic surgery after MRI confirmed the presence of 6 anterior cruciate ligament (ACL) tears, 11 meniscal tears, and 5 normal menisci in this group. Four blinded readers, experienced in MRI of the knee, evaluated the images. The MRI datasets were then loaded onto a three-dimensional workstation and interpreted by the same readers using MPR. The MRI findings were correlated with arthroscopy. RESULTS: For diagnosis of tears of the ACL, sensitivity was 96% and specificity was 100% for both films and MPR. For detecting meniscal tears, sensitivity was 55% and specificity was 90%, using the filmed images, versus 64% and 85%, respectively, with MPR. These differences were not statistically significant by the sign test. Total time (technologist processing time plus radiologist reading time) for MPR was greater than for film interpretation by a factor of 1.12 (P < .05), and radiologist reading time for MPR was greater by a factor of 1.88 (P < .05). CONCLUSIONS: For sagittal three-dimensional FISP MRI datasets, real-time MPR is comparable with film interpretation for evaluation of ACL and meniscal injuries, but it increases the time required for diagnosis. PMID- 8444571 TI - Effect of image display on the quality of multiplanar reconstruction of computed tomography data. AB - RATIONALE AND OBJECTIVES: The objective of this study is to determine whether the use of edge-enhancement post-processing filters was useful in the computed tomographic (CT) multiplanar evaluation of skeletal trauma. METHODS: The group consisted of a series of 10 cases of skeletal trauma (3 cases of acetabular fractures, 3 cases of tibial plateau fractures, and 4 cases of ankle fractures). All patients had a CT scan using a scan protocol of 4-mm collimation and 3-mm interscan interval. All transaxial images were reconstructed with both a standard algorithm and with an edge-enhancement filter. The images from each group were then reconstructed into coronal and sagittal planes. Three individuals independently reviewed each case and compared image pairs to determine whether images using an edge-enhancement filter were of better or worse quality than standard images. RESULTS: The reviewers found the images with edge-enhancement to be equal to or superior to images reconstructed with a standard algorithm, regardless of the image plane chosen. This bias was especially true in cases of hip and ankle trauma. CONCLUSIONS: When CT supplemented by multiplanar imaging is used in patients with skeletal trauma, image data reconstruction should be done with an edge-enhancement filter to optimize image detail. PMID- 8444572 TI - Biodegradable starch microspheres for cerebral arterial embolization. AB - RATIONALE AND OBJECTIVES: Various materials have been used to perform intracerebral and cervical arterial embolization for head and neck tumors and vascular malformations. This preliminary prospective study was designed to analyze the clinical and histopathologic consequences of arterial embolization into the brain using biodegradable starch microspheres. METHODS: A new arterial embolization procedure which ensured the integrity of the common and internal carotid arteries, without modifying the arterial flow, was designed. The procedure allowed for cerebral arterial microembolization in 20 Sprague-Dawley rats. Various amounts of biodegradable starch microspheres (Spherex) were introduced into the brain via the left external carotid artery. RESULTS AND CONCLUSIONS: Clinical and histopathologic results suggested that: 1) consequences of cerebral embolization using biodegradable starch microspheres are related to the amount of material embolized; and 2) Spherex microspheres behave differently from degradable microspheres in the brain. Despite the rapid biodegradability of the material, permanent damage from ischemia to the brain was noted. PMID- 8444573 TI - Technology assessment in diagnostic imaging. A proposal for a phased approach to evaluating radiology research. AB - RATIONALE AND OBJECTIVES: The authors propose an objective basis for critical evaluation of research trends and define and analyze a sample of radiology studies according to research phase. METHODS: A random sample of 146 original diagnostic studies from two radiology journals was categorized according to phase, modality, and design by three physician reviewers, collated with a microcomputer database, and analyzed using an SAS program. RESULTS: Phase 1 studies (technical evaluation) constituted 18.5% of publications: phase 2 (standardization and tissue characterization), 10.3%; phase 3 (spectrum of appearances), 40.4%; phase 4 (diagnostic efficacy), 21.2%; and phase 5 (clinical evaluation), 9.6%. Of 48 diagnostic efficacy studies, 42% were prospective (versus 35% for the total sample), 38% were controlled (median sample size, 53 [versus 30 for the total sample]). Only 27% of the 48 diagnostic efficacy studies were externally funded. Research in magnetic resonance imaging (MRI), which comprised 45% of all publications, was oriented toward phase 1 (32%) rather than phase 5 studies (0%). Phase 5 studies were the focus of 18% and 8% of ultrasound (US) and computed tomography (CT) studies, respectively. There were more prospective, controlled efficacy studies in US than in MRI or CT. CONCLUSIONS: Analyses of research trends will be facilitated by use of a standard taxonomy which adopts a modality-based, phased approach. PMID- 8444574 TI - Prediction of teleradiology system throughput by discrete event-driven, block oriented network simulation. PMID- 8444575 TI - Development of a computer-assisted instructional tool for evaluation and treatment of renal masses. An experiment in hypermedia. AB - RATIONALE AND OBJECTIVES: Using a personal computer and a commercially available "authoring" application, the authors constructed an interactive hypermedia teaching tool for the evaluation and management of renal masses. METHODS AND RESULTS: Through a series of questions, images, illustrations, hypertext, and graphical flow charts, the user reviews the spectrum of renal masses, including neoplasms, inflammatory disease, cysts, and "pseudomasses." The various imaging modalities (computed tomography [CT], ultrasound [US], magnetic resonance imaging [MRI], and angiography) are illustrated, with selective advantages and disadvantages to each technique highlighted. Selected algorithms for evaluation and treatment of masses are provided. Text, questions, a teaching file, and algorithms form the major sections of the program. Numerous links within and between the major sections of the program, a capacity unique to hypermedia, allow for nonlinear entry into the program, tailored to the individual user. CONCLUSIONS: Preliminarily, medical students and residents have responded positively to this hypermedia project. Furthermore, their comments and criticism have provided important feedback for future updates and enhancements. PMID- 8444576 TI - Intramural gastric abscess mimicking leiomyoma. Clinical, radiologic, and pathologic features of an unusual gastric lesion. PMID- 8444577 TI - Proximal renal tubular vacuolization induced by iodinated contrast media, or so called "osmotic nephrosis". PMID- 8444578 TI - 1000 consecutive laparoscopies in gynaecological practice. AB - One thousand consecutive laparoscopies were performed by an individual team at University College Hospital, Galway from 1982 to 1990. The mean age of the patients was 34 years (range 15-61). The majority (702) were undertaken for tubal ligation, followed by investigation of infertility (125), pelvic pain (87) and suspected ectopic pregnancy (41). Laparotomies were avoided in 77 patients with pelvic pain and in 26 patients with suspected ectopic pregnancy. A further 73 patients had surgical procedures performed laparoscopically. There were no failed laparoscopies. Minor complications occurred in 1.3% of patients. The commonest difficulty encountered was failed first attempt at pneumoperitoneum (4%). Two patients required laparotomy following laparoscopy, because of intra-abdominal bleeding. Readmissions occurred in 7 patients but again no serious sequelae were recorded. The use of the laparoscope in general gynaecological practice is examined with the safety, diagnostic and therapeutic facilities of the procedure explored. PMID- 8444579 TI - Delay and hospitalisation with acute myocardial infarction. AB - We examined patient behaviour and the components of delay to hospitalisation in 149 consecutive cases of proven acute myocardial infarction (AMI) prospectively. The median total delay from onset of chest pain to hospitalisation was 210 mns (range 5 mns to 7 days). The median delay before seeking medical help was 105 mns. Seventy-eight patients (52%) contacted a G.P. Median delay to G.P. contact was 15 mns. The median delay in transportation to hospital was 20 mns. There was no evident diurnal variation in the onset of symptoms. There was no significant differences in help seeking delay between the sexes, between young and old or between those with a previous history of ischaemic heart disease similar to studies in the U.S. and U.K. Patient delay to seeking help remains the major and most crucial component of delay in treating AMI. PMID- 8444580 TI - Experiences with octreotide in acromegaly. AB - We report experiences in 3 patients with acromegaly while using the somatostatin analogue octreotide. In case 1, a 44 year old male developed pneumococcal meningitis 3 months after having transphenoidal surgery for a pituitary tumour. This occurred with the re-emergence of communication between the surgical tract and the C.S.F. In case 2 a 52 year old male with insulin resistant diabetes mellitus requiring 240 units/day, with greatly elevated growth hormone concentrations was able to stop insulin within 5 days of starting octreotide. In case 3, a 52 year old male with sleep apnoea syndrome, respiratory failure and resistant heart failure made a dramatic improvement which is maintained 2 years later. All cases were associated with substantial falls in growth hormone and insulin like growth factor-1 concentrations. PMID- 8444581 TI - Intensive care in an Irish district general hospital--a three year review. AB - The International Missionary Training Hospital is a 340-bed acute general hospital with maternity and paediatric units. It serves a population of 120,000 people within the North Eastern Health Board Area and has approximately 14,000 admissions each year. This report retrospectively reviews the activity of a three bedded, Intensive Therapy Unit (ITU) over the three year period July 1987-June 1990. 805 patients (1.9% of hospital admissions) with an average age of 55 +/- 22 years (mean +/- SD, range 14-94 years) were admitted to the unit. There were 458 males (57%) and 347 females (43%). 68% of the patients were admitted from the general wards and the remainder from the accident unit. 59% of the admissions were immediate postoperative cases. 82% of patients had APACHE scores less than 20. There was a wide diversity of medical and surgical diagnoses requiring treatment. 219 cases required one or more systems to be supported and 586 (73%) were admitted as high dependency cases. For those requiring ventilation, the average ventilation time was 3.2 days (range 0.5-23 days). The average length of stay within in the unit was 2.3 days (range 1-23 days). 86% of the patients were discharged to the wards, 11% died and 3% were transferred to external specialist care facilities. ITU's in district general hospitals serve as both critical care areas and high dependency units. In our opinion they produce a positive contribution to progressive patient care for high risk medical and surgical patients. PMID- 8444582 TI - Infant feeding practices. AB - This study was done on a population of 877 mothers over a five month period. Interviews were held on the first day after delivery and on the day of discharge. Mothers were questioned on their infant feeding practice and on the influences which led them to their choice of feed types. Follow up studies were done in subsequent months on randomly selected populations of breast feeders (103) and bottle feeders (170) to determine duration of breast feeding after discharge from hospital; the factors contributing to cessation of breast feeding; the measure of satisfaction with the brand initially chosen and the factors which caused mothers to change from one brand to another. The salient finding is that 36% breast feed initially and that up to 10% of the total are still doing so five months later. The other findings are discussed and their significance stated. PMID- 8444583 TI - GP trainees and MMR immunisation. AB - Three months after the launch of the MMR programme in the United Kingdom and the Republic of Ireland, a postal questionnaire was sent to all GP scheme trainees in both Northern Ireland and the Republic of Ireland. The response rate was 81%. All trainees were enthusiastic about promoting MMR immunisation; with 27% favouring compulsory immunisation. 9% had never seen a patient with measles. This did not alter their attitude towards the beneficial effects of MMR immunisation. Of pre practice year trainees 26% felt their level of knowledge of immunisation was inadequate, 59% claimed to have received no education on immunisation during their vocational training to date. This may reflects deficiencies in their medical curriculum to-date. 95% of third-year trainees indicated that their practice experience had been the source of at least some of their education on immunisation. Only 46% of trainees in the Republic of Ireland were aware of their Department of Health's aims in launching the MMR immunisation campaign. PMID- 8444584 TI - Coronary risk factors in Belfast schoolchildren. AB - Although Northern Ireland leads the world in terms of coronary heart disease mortality, the prevalence of coronary risk factors in the childhood population is largely unknown. The aims of the present study were to assess the feasibility of collecting this data and to undertake a preliminary investigation of risk factor status. One hundred and three out of 154 first year pupils (67%), mean age 12.3 years from a Belfast secondary school had their height, weight, pubertal status and blood pressure estimated. Blood samples were analysed for serum cholesterol and thiocyanate in 99 children. 31% had elevated cholesterol, 13% had raised blood pressure, 13% were overweight and 5% were identified as smokers. There appeared to be relatively high risk factor levels with at least one risk factor present in 45% of children. No difficulties arose in compliance with the test protocol suggesting that coronary profiling in children on a large-scale is feasible. On the basis of these results, we feel that coronary risk factor status in Northern Irish children needs further evaluation. PMID- 8444585 TI - Breast screening--a surgeon's perspective. PMID- 8444587 TI - Childhood asthma, can admissions be avoided? AB - Since admissions with asthma continue to increase and account for considerable morbidity, we chose to prospectively study asthma admissions over a one year period to assess the severity of patients' asthma, their need for treatment available only in hospital, and to assess the adequacy of their prehospital treatment. A study proforma was completed soon after the admission of each child. Data gathered between the 1st January and 31st December 1990 are presented. There were 105 children admitted, two-thirds of those were boys and just over half were aged less than 5 years. Eighty-seven children had a previous diagnosis of asthma. Overall the attacks were not severe, only 10 patients were treated with intravenous medication and 18 children required continuous oxygen. Sixteen patients required hospitalisation for more than 48 hours, the remainder were discharged within 2 days. Suboptimal prehospital care was identified in a third of patients, inappropriate management of the acute attack, failure of adequate prophylactic medication and non-compliance with prescribed regimes were common. In our hospital, admissions with acute severe asthma have declined in 1990, attention to simple treatment schedules may further reduce hospitalisation. PMID- 8444586 TI - An audit of hypertensive care in general practice. AB - This mainly urban based study of hypertensive care in general practice consisted of 5,400 patients of these 287 individuals were diagnosed as being hypertensive, a practice prevalence of 5.31%. Among those between 30-80 years (2456 patients) there were 265 hypertensives, a prevalence of 10.8%. The overall male: female ration was 1:1.8. Hospitals were involved in the management of 53.9% of the hypertensives. The use of WHO criteria to make the diagnosis had increased from 38.6% to 59% over the past five years. The completence of history taking and relevant investigations was suboptimal, 78.9% of the hypertensives had their BP checked in the previous year. Management of hypertension is similar to other practices who have performed audits. There is room for improving standards in all clinical activities relating to hypertension. PMID- 8444588 TI - Surgery for Crohn's disease. AB - In the last 12 years, 72 operations have been performed on 41 patients for Crohn's disease in this hospital. The patients were predominantly young (mean age 32 yrs) and there were more females than males. 28 had ileocolic disease, three small intestinal, two pan-enteric and eight colonic. Pain (in 76%), diarrhoea (56%) and weight loss (66%) were the main presenting symptoms. Diarrhoea occurred in all those with colonic disease, but in only 43% of those with ileocolic disease. A right hemicolectomy (28 patients), colonic resection (12) and small intestinal resection (9) were the commonest operations. There were no deaths. 22 patients had a total of 26 complications after surgery, eight necessitating further surgery. The mean post-operative stay was 15 days, being lowest in those with ileocolic disease. 19 patients have required only one operation, with a mean follow-up of 5.3 years. These patients also had significantly less complications (p < 0.05). Half of the patients requiring surgery for Crohn's disease have done very well. The other half require many operations and have a substantial morbidity. PMID- 8444589 TI - Palpation of a pyloric tumour. PMID- 8444590 TI - Adenocarcinoma of the lung in association with chronic sarcoidosis. AB - Adenocarcinoma of the lung occurred three years after the diagnosis of pulmonary and cutaneous sarcoidosis. The combination of pulmonary sarcoidosis and carcinoma, which may present diagnostic difficulties is rarely reported. As with other fibrosing lung diseases, however, chronic fibrosing sarcoidosis may predispose to adenocarcinoma. PMID- 8444591 TI - Antenatal ultrasound diagnosis of fetal hydrometrocolpos. PMID- 8444592 TI - The sports' clinic: a one year review of new referrals. AB - The new presentations to the Cork Sports' Clinic over a one year period 1.1.90 to 31.12.90 were examined. We looked at the age and sex distribution of the presenting population, the type and site of injury, the sport played and the treatment and outcome of the injury. 126 new cases presented in 1990. 107 (85%) were male. The three commonest sports featured were all contact ones. The knee was the commonest site of injury (46.8% of cases) with 73.1% of injuries occurring in the lower limb. 73% of cases presented between the ages of 15 to 29 years. The majority of patients had improved on follow-up. Nine were referred to an orthopaedic service-five fractures and four serious ligamental injuries. The Cork Sports' Clinic works adjacent to a busy accident and emergency department. There is a definite need for our clinic in conjunction with the casualty department. PMID- 8444593 TI - Endogenous depression: current classifications and new treatments. PMID- 8444594 TI - Preventable perioperative mortality from colorectal cancer. AB - Of 271 patients with primary colorectal cancer, 70 (26%) had detectable hepatic metastases. A primary tumour resection was possible for 225 (83%) of patients overall. Of the 46 patients with non resectable tumours, 38 (82%) had hepatic metastases. 23 (33%) of the patients with Dukes' D tumours died perioperatively relative to 13 (6%) of those with localised tumours (p < .001). Seventeen (70%) of the twenty three patients with Dukes' D cancers who died perioperatively had locally advanced disease but were not obstructed and had neither a resection or a stoma performed. Perioperative mortality is unacceptably high in patients with hepatic metastases but may be reduced by more specialised investigation of patients with suspected advanced disease to assess the degree of local dissemination and liver seeding prior to considering laparotomy. PMID- 8444595 TI - Prevalence of hepatitis C antibodies in patients with liver disorders in the west of Ireland. AB - During the period from August 1989 to October 1990, 93 patients living in the West of Ireland were screened for Hepatitis C antibodies (Anti HVC) using a commercially available assay. The tests were performed because of abnormal liver function tests (LFTs) or clinical suspicion of Hepatitis C. Nine positive results were obtained (10.3%) seven of whom had a history of transfusion of blood or a blood product. The study revealed that the prevalence of anti HCV was low in patients with chronic liver diseases, in comparison to reported prevalence rates in other parts of the world and that blood transfusion was the commonest predisposing factor to acquisition of anti HCV in this area. PMID- 8444596 TI - Successful pregnancy in two sisters with Wolfram syndrome. AB - Wolfram's Syndrome is a rare disorder comprising diabetes insipidus, diabetes mellitus, optic atrophy and high tone sensineural deafness. Successful pregnancy is extremely rare and has not previously been reported in siblings with this disorder. We report on two Irish sisters suffering from Wolfram's syndrome who have given birth to three healthy male infants. PMID- 8444597 TI - Congenital dislocation of the patella in Rubinstein Taybi syndrome. AB - Two patients with Rubinstein Taybi Syndrome (RTS) were found to have congenital dislocation of the patella (CDP). The dislocation was bilateral in one patient. Both underwent surgical reduction and stabilisation. The dislocation recurred in one patient who had associated genu valgum and external tibial torsion at the time of stabilisation. We feel that early diagnosis of CDP in patients with RTS is important to help early mobilisation and avoid secondary degenerative knee changes occurring. PMID- 8444598 TI - Babinski's sign. PMID- 8444600 TI - Panic disorder. PMID- 8444599 TI - Gaucher's disease with haematological complications. PMID- 8444601 TI - The management of sleep disorders. PMID- 8444602 TI - Clinical applications of the combi probe--how do transcutaneous blood gas measurements perform in clinical practice? PMID- 8444603 TI - Death in a country practice: an audit cycle. PMID- 8444604 TI - Premature pubarche--a diagnostic dilemma? PMID- 8444605 TI - Management of stomas. PMID- 8444606 TI - Infection and the role of the clinical microbiologist. PMID- 8444607 TI - The role of infectious agents in peptic ulcers and gastritis. PMID- 8444608 TI - Breast-feeding versus formula: cost comparison. AB - Peterkin and Walker published in 1976 a cost estimate of feeding a baby in the U.S. At that time, they found there was little difference in cost between breast feeding and formula feeding. Since then, however, the cost of formula has risen drastically--more than 150% during the 1980s. One researcher estimated that food and feeding equipment cost $855 in the first year. Whereas the cost of formula is quite apparent when a family buys it, the cost of breast-feeding is hidden. PMID- 8444609 TI - "Buy right". PMID- 8444610 TI - Health care and more health care. PMID- 8444611 TI - Health care in the United States: the need for a new paradigm. PMID- 8444612 TI - The role of governing boards in multihospital systems. AB - Governance is a complicated, sensitive, and complex element of management. When exercised by individuals not thoroughly conversant with the intricacies of the health care business, it can lead to a variety of organizational and operational tragedies. Appropriate understanding and implementation of strategic governance and operational governance will greatly strengthen and enhance the governance function in hospitals and hospital systems. PMID- 8444613 TI - Managing partnerships: the perspective of a rural hospital cooperative. AB - While a dairy cooperative provided the bylaws, managing a cooperative of rural hospitals has been a learn-as-you-go experience. This article presents the management principles that have been learned over the last 13 years. Its experience suggests that developing and managing partnerships requires behaviors different from those typically associated with the management of individual organizations. PMID- 8444614 TI - Organizational cultures, strategies, and commitments in health care organizations. AB - Cultural elements called norms and values affect organizational commitment and job satisfaction of managers and executive secretaries in this study of 13 health care organizations. Results also show that organizations pursuing a consistent strategy possess strong cultures, while organizations with an inconsistent strategy exhibit weak cultures. PMID- 8444615 TI - Critical factors in recruiting health maintenance organization physicians. AB - What factors facilitate successful physician recruiting by health care organizations? Answers surfaced in a study of physician recruiting by a large HMO in the Southwest. Professional networking and word-of-mouth advertising appear to be the prominent means by which physicians learn of attractive staff positions. Successful recruiting also depends on a practice setting that fosters quality care, emphasis on patient care delivery, and collegial interaction. PMID- 8444616 TI - Critical factors for successful hospital-based case management. AB - Six hospitals were funded to develop programs for long-term case management. Factors that should be considered when developing hospital-based case management are discussed within three areas: organizational placement, program management, and financial viability. PMID- 8444617 TI - Getting to go in managed care. AB - Managed care has clearly pointed the way to bringing health care costs under control. But the providers themselves, right now, must either take on the responsibility of more directly managing care, bringing utilization down, and sharing in the rewards, or they could find themselves asked to sacrifice while intermediaries prosper. PMID- 8444618 TI - Improving hospital cost accounting with activity-based costing. AB - In this article, activity-based costing, an approach that has proved to be an improvement over the conventional costing system in product costing, is introduced. By combining activity-based costing with standard costing, health care administrators can better plan and control the costs of health services provided while ensuring that the organization's bottom line is healthy. PMID- 8444619 TI - Nursing at a crossroads: managing without facts. AB - Literature on variables relating to nursing structures, nursing support systems, and patient classification systems contains discrepancies in definitions and methods. This lack of systematic research results in uncertainty and renders comparisons untenable. PMID- 8444620 TI - An epidemiological approach to quality assurance in the hospital. AB - This article discusses epidemiological methodology: comparing rates, confounding, the use of confidence intervals, Bayes' theorem, and occurrence screening. An appreciation of the limits of epidemiological methods will provide the manager with realistic expectations of the quality assurance process. PMID- 8444621 TI - Coping with rheumatoid arthritis: is one problem the same as another? AB - This study examined how individuals with rheumatoid arthritis (RA) cope with illness-related problems in four different areas: daily activities, leisure activities, work, and social relationships. Eighty-five people with RA took part in the study. They participated in an in-depth interview that focused on the types of changes they had experienced in their lives as a result of their arthritis and how they had coped with these changes. Audiotapes of the interviews were transcribed and content analyzed to assess participants' coping behavior. In addition, standardized measures of psychological and physical functioning were administered shortly following the original interview and at a 4-month follow-up. Three major findings emerged. First, people relied less heavily on behavioral coping strategies when dealing with problems involving social relationships than when dealing with problems involving daily activities, leisure activities, or work. Second, there was little consistency in individuals' use of either cognitive or behavioral strategies across different problem areas. Finally, individuals who exhibited limited flexibility in their coping responses experienced poorer psychological functioning compared with more flexible copers. Implications of these findings for health education practice and future research on coping with RA are discussed. PMID- 8444622 TI - Arthritis self-management studies: a twelve-year review. PMID- 8444623 TI - Specific psychosocial and behavioral outcomes from the systemic lupus erythematosus self-help course. AB - This study tested hypotheses about the consistency of specified outcomes with strength of program treatment indexed by time spent in a given activity in the Systemic Lupus Erythematosus Self-Help (SLESH) course. Participants had significant increases in enabling skills and in use of relaxation and exercise activities. Participants also had significantly less depression. Consistency between amount of time spent in class and significant changes over time was demonstrated by analysis of treatment strength-response for perception of limitations, depression, enabling skill and for use of rest, relaxation, heat, and exercise activities. PMID- 8444625 TI - Teaching and social support: effects on knowledge, attitudes, and behaviors to prevent low back injuries in industry. AB - An educational program designed to reduce low back injuries was modeled after several well-known back schools and taught to postal workers in a randomized trial of about 4,000 workers. Physical therapists taught 3 hours of class sessions, including knowledge, skills, and individual work station assessment, to small groups of workers and supervisors, with reinforcement every 6 months afterward. At 2 1/2 years, a random sample of 209 workers was surveyed for program impact on intermediate outcomes. We observed increased knowledge among experimental unit workers, but no significant improvements in behaviors associated with back health or in proportion of workers with tired backs. Experimental unit workers who had received training by the time of the survey were less likely to report helping/reinforcement for healthy behaviors than controls or untrained experimental unit workers. The program might have led trained workers to perceive a lack of support and reinforcement for back safety among coworkers and supervisors by sensitizing them to what is possible and raising expectations. There appeared to be group social effects in the dissemination of knowledge and perhaps of helpful behaviors; however, it is apparent that worker social support for change in health behaviors is a complex phenomenon that cannot always be relied upon to enhance program goals. PMID- 8444624 TI - Arthritis education: opportunities and state of the art. AB - Health education research in arthritis and musculoskeletal disease experienced extraordinary growth in the 1980s. In this article we discuss opportunities for health education in arthritis and musculoskeletal disease, and the effectiveness of evaluated programs to influence knowledge, behavior, and health status of persons with arthritis. Additionally, we review developments in theory and trends in research that we expect to be influential in the next decade. Educational opportunities for primary prevention of arthritis are limited. However, a large variety of organized programs, planned according to commonly accepted principles of education, psychology, and psychotherapy, and applied consistently by personnel with some kind of training, have been able to produce desirable changes in knowledge, behavior, and health outcome in arthritis patients, over and above the medical treatment and incidental education to which they have already been exposed. As a result, national dissemination of programs and standards for arthritis patient education is in progress. In the next decade, researchers will increasingly turn to new populations and methods of delivery, investigation of conditions less well studied, such as osteoporosis, education of patients in generic communication and coping skills, and development of arthritis-specific applications of theory, especially in areas such as social support, control and helplessness, cognitive processing, and pain management. PMID- 8444626 TI - A walking education program for patients with osteoarthritis of the knee: theory and intervention strategies. AB - Walking is an ideal physical activity for patients with osteoarthritis because it can help to improve functional status without exacerbating pain or necessitating an increase in the use of medication. Although patient education programs designed to encourage walking have become increasingly important in the management of this condition, there is no single synthesis or other published source of theory and intervention strategies to guide the practitioner in the development of such programs. This paper describes a hospital-based patient education program designed to enhance the functional capacity of who have osteoarthritis of the knee by encouraging the adoption and maintenance of walking. The paper describes the goals, objectives, process, and impact of the program; the principal theoretical model utilized in the design of the program; and how concepts and intervention strategies from the literatures on patient compliance and patient education, exercise compliance, behavioral psychology, and relapse prevention have been operationalized and integrated in a walking program that we have evaluated for safety and efficacy. PMID- 8444627 TI - Exercise maintenance of persons with arthritis after participation in a class experience. AB - This study investigated factors related to an initial exercise experience to explain exercise maintenance in 120 adults with rheumatoid arthritis or osteoarthritis. Integral secondary analysis was used to incorporate data from a prospective, controlled trial of exercise (Minor et al.: Arthritis Rheum 32:1396, 1989) with data collected at 18 months follow-up. The dependent variable was self directed exercise (min/wk) reported at 3, 9, and 18 or more months after exercise class participation. Predictor variables included physical, psychosocial, disease, and programmatic factors. The all possible regressions search procedure resulted in three explanatory models (p = .0001). At 3 months the model (R2 = .45) included initial aerobic capacity, depression, and anxiety; and changes in depression and social activity. The 9-month model (R2 = .35) consisted of initial anxiety and physical activity, change in depression, support of friends for exercise, and exercise behavior at prior assessment. At 18 or more months (R2 = .42), model variables were initial aerobic capacity, change in pain, and exercise behavior at the two prior assessments. Neither disease nor program factors appeared as significant. This limited study indicates that factors associated with exercise behavior in this sample are similar to those in the general population; explanatory factors change over time, and changes ascribed to a trial behavior may influence subsequent decision making. PMID- 8444628 TI - Social support interventions for rheumatoid arthritis patients: the cart before the horse? AB - Enthusiasm about the potential of social support to promote successful adaptation to chronic illness has already led to support interventions for arthritis patients designed to increase coping ability, reduce the need for professional mental health services, and limit periods of disability. But have we put the cart before the horse? Do these interventions achieve these goals? Existing interventions are reviewed, and a number of research issues are addressed from within an ecological framework, including the content of support interventions, the source of support, the type of support provided, support as an intervention variable versus outcome, and the need to target interventions not only to patients but to their family members and health professionals. It is suggested that future interventions be more theoretically grounded. PMID- 8444630 TI - Ventronics 5520, 5522, and 5523 ventilarms: failure to detect low airway pressure. PMID- 8444629 TI - OSHA's bloodborne pathogens standard: analysis and recommendations. AB - Just over a year ago, the Occupational Safety and Health Administration (OSHA) issued the final bloodborne pathogens standard, "Occupational Exposure to Bloodborne Pathogens; Final Rule," which requires healthcare institutions to protect their employees from all occupational exposure to bloodborne pathogens." According to OSHA, the only criterion for applying the standard is the likelihood of exposure to blood and other potentially infectious materials (OPIMs). Thus, the standard is designed to protect all vulnerable personnel, from the clinical engineers who service contaminated equipment to the staff in clinical laboratories, patient care or treatment areas, and housekeeping and laundry services--any location where the nature of the work poses the risk of exposure to bloodborne pathogens. All department heads and employees must have access to the standard and should carefully review our analysis of the regulations and recommendations for implementing them, as presented in this special issue of Health Devices. The standard is aimed at protecting employees from occupational exposure to all bloodborne pathogens and, especially, to the human immunodeficiency virus (HIV) and the hepatitis B virus (HBV)--the most infamous pathogens transmitted through occupational exposure to blood and body fluids. Other bloodborne diseases referenced by OSHA in the preamble to the standard include arboviral infections, babesiosis, brucellosis, Creutzfeldt-Jakob disease, hepatitis C, human T-lymphotropic virus type I, leptospirosis, malaria, relapsing fever, syphilis, and viral hemorrhagic fever. In this issue, we provide a clinical overview of HIV and HBV and the diseases they cause, as well as a brief discussion of other bloodborne pathogens; an analysis of the most significant regulations affecting hospitals; and our recommendations for compliance. The recommendations presented in this article do not exhaust the possibilities for reducing exposure and complying with the standard. We invite you to communicate your ideas and practices regarding compliance issues to the ECRI-sponsored Center for Healthcare Environmental Management (CHEM) for possible inclusion in a future update to its loose-leaf reference publication, the Healthcare Environmental Management System. We wish to acknowledge CHEM's contribution in developing this special report, which was reviewed by the Centers for Disease Control and Prevention (CDC), the National Institute for Occupational Safety and Health (NIOSH), and OSHA. Also see "CDC's Recommendations for Hepatitis B Vaccination and Postexposure Follow-up" and "A Minimal Training Syllabus" in this issue. PMID- 8444631 TI - Aequitron 9216 hospital apnea monitors: electrostatic discharge sensitivity. PMID- 8444632 TI - Intra-aortic balloon pumps: inspection and infrequent use. PMID- 8444633 TI - Disposable blood pressure transducers: calibration methods. PMID- 8444634 TI - ECG electrodes: selection practices. PMID- 8444635 TI - ECG electrodes: use on resuscitation carts. PMID- 8444636 TI - International Medical Systems Exposcop Plus mobil C-arm system. PMID- 8444638 TI - Damaged Allied Healthcare Products Gomco circumcision clamps. PMID- 8444637 TI - Microbiology systems. PMID- 8444639 TI - Influence of growth temperature on the production of extracellular virulence factors and pathogenicity of environmental and human strains of Aeromonas hydrophila. AB - The biochemical properties, virulence for mice and trout, and the extracellular virulence factors at 28 degrees and 37 degrees C of 11 environmental and nine human strains of Aeromonas hydrophila were compared. All the environmental isolates and four of the human group were virulent for trout at 3 x 10(7) cfu, but only human strains were able to cause death or lesions in mice by the intramuscular route. Extracellular virulence factors such as haemolysins, cytotoxins and proteases were also investigated in supernatant fluids of cultures grown at 28 degrees C and 37 degrees C. The production of haemolysins, caseinases, elastases and growth yields of environmental strains decreased sharply during cultivation at 37 degrees C but cytotoxins were produced to the same extent, or slightly less, than at 28 degrees C. The human strains differed from the environmental strains in response to growth temperatures: protease activity decreased at 37 degrees C, although growth yield was not affected, but more haemolysins and cytotoxins were produced by the virulent strains at this temperature than at 28 degrees C. Sodium caseinate SDS-PAGE of culture supernatant fluids of selected human strains revealed that temperature selectively inhibited the production of certain proteases. PMID- 8444640 TI - The production of antifungal volatiles by Bacillus subtilis. AB - A strain of Bacillus subtilis which produces an antibiotic metabolite was also found to produce a volatile compound(s) which was antifungal to Rhizoctonia solani and Pythium ultimum. Growth of the fungi was severely impaired in the presence of the volatiles and physiological abnormalities of the hyphae were observed, including hyphal distortion and vacuolation. A range of media were tested for volatile production and potato dextrose agar (PDA) was found to be the most active. Temperature had a considerable effect on antifungal volatile activity with the greatest inhibition occurring at 30 degrees C. Addition of iron (III) chloride to Sabouraud's glucose agar (SGA) also enhanced the antifungal effect. The volatiles were found to be water soluble and remained active when trapped in SGA. PMID- 8444642 TI - Production and characterization of antibacterial compounds produced by Pediococcus damnosus and Pediococcus pentosaceus. AB - The broad-spectrum antibacterial activity exhibited by three Pediococcus strains isolated from beer was preliminarily characterized. Factors affecting the production rate of bacterial inhibitors were screened and the effects of simultaneous cultivation of Lactococcus and Pediococcus on the production of inhibitory substances were studied. The antibacterial activity against a range of Gram-negative test organisms was not affected by catalase or proteolytic enzymes and was extremely thermotolerant. Production of the inhibitors was maximal between pH 6 and pH 7. A growth medium containing unhopped end-fermented wort was beneficial for the production of inhibitors, particularly by the Pediococcus damnosus strain, and anaerobic growth conditions were preferable. The antagonistic activity against the Gram-negative test organism Salmonella infantis could be demonstrated after an incubation period of only 2 d if the Pediococcus and Lactococcus strains were incubated simultaneously as a mixed population. PMID- 8444641 TI - Effects of some ionophore antibiotics and polyoxins on the growth of anaerobic rumen fungi. AB - The growth of mixed rumen fungi in vitro was suppressed by both ionophore antibiotics (salinomycin, monensin and portmicin) and polyoxins (polyoxin B and D: inhibitors of chitin synthesis). The fungistatic effect of the ionophores on a Piromonas spp. was more pronounced than on a Neocallimastix spp. The polyoxins, however, were more potent fungistatically against the Neocallimastix spp. than the Piromonas spp. Higher concentrations of the polyoxins were required to elicit the same effect as that observed with the ionophores. Salinomycin administration decreased fungal count in the rumen of sheep, but fungal count increased after the cessation of the feeding of the antibiotic. Polyoxin D also suppressed the growth of fungi in vivo, but the effect was short-lived. Nevertheless, both bacterial and protozoal counts tended to increase during and after the administration of polyoxin D. Total volatile fatty acid concentrations in the rumen tended to increase during the period of polyoxin D administration. This increasing tendency was maintained for 10 d after the cessation of antibiotic administration. Offering polyoxin D to sheep increased production of propionate (P < 0.05), while decreasing that of acetate. The results indicate that the rumen fungi are sensitive to chitin synthesis inhibitors as well as ionophores, and are essential members of microbes in the rumen ecosystem. PMID- 8444643 TI - Freeze-dried mixed cultures as reference samples in quantitative and qualitative microbiological examinations of food. AB - Two simulated food samples in the form of mixtures of bacteria, freeze-dried in small glass vials, were tested for their suitability as reference materials in food microbiology. Stability and homogeneity of the samples were assessed during a 1 year period when stored at 2-6 degrees C. Samples were examined for aerobic plate counts, coliform counts, Staphylococcus aureus, Clostridium perfringens, Bacillus cereus, enterococci, yeasts and salmonellas. The samples were homogeneous but the number of colony forming units of some organisms declined during the time period studied. The maximum rate of decline (0.8 log units per year) was observed for the coliforms. Precision estimates (reproducibility and repeatability) for the different testing methods used are given. When compared with these data, the rate of decline was considered to be of less importance. PMID- 8444645 TI - Methods for the detection of thermotolerant campylobacters in foods: results of an inter-laboratory study. AB - An inter-laboratory comparison of three methods for the detection of thermotolerant campylobacters is described. One of two proposed by the International Standards Organisation was significantly better for detecting campylobacters in minced chicken skin naturally contaminated at levels of either 2 or 10 cells per 10 g, but involved extensive manipulations not likely to be well received in a busy laboratory. This method yielded 18% false negative results compared with 48-54% for the other two but also gave 8% false positive results. Pre-enrichment of samples with a gradual addition of antibiotics to suppress competing organisms seemed to improve the recovery of campylobacters, as did a non-selective blood agar isolation medium used in combination with a membrane filtration technique. PMID- 8444644 TI - Detection of Aeromonas hydrophila in food with an enzyme-linked immunosorbent assay. AB - A microtitration plate, antibody capture, enzyme-linked immunosorbent assay was developed for the detection of Aeromonas hydrophila serotype O: 11 (highly virulent strains). The assay utilizes a detector antibody which shows no cross reactions with Aeromonas strains other than serotype O: 11 or non-Aeromonas competing organisms. The detector antibody is mixed with the sample and incubated for 1 h, microcentrifuged and the supernatant fluid (unadsorbed antibody) titred in a microtitre plate coated with A. hydrophila cells from serotype O: 11. All the A. hydrophila strains from serotype O: 11 tested reacted strongly with the detector antibody. Also by culturing and performing the immunoassay with the detector antibody we established and quantified the presence of A. hydrophila O: 11 in different foods. PMID- 8444646 TI - Interactions among xerophilic fungi associated with dried salted fish. AB - Interactions were investigated among five xerophilic fungi, Polypaecilum pisce, Basipetospora halophila, Eurotium rubrum, Aspergillus wentii and A. penicillioides, isolated from Indonesian dried salted fish. A range of water activities (aw) (0.98, 0.95, 0.90 and 0.84) and temperatures (15 degrees, 25 degrees and 30 degrees C) were studied on agar media in Petri dishes, and with dried fish as a substrate at 0.90 and 0.84 aw at 30 degrees C. Generally, the fungi exhibited one of two interaction types: mutual inhibition on contact, or inhibition of one or both species on contact, with the inhibited species continuing to grow at a significantly reduced rate. On glucose-based agar media A. wentii and E. rubrum were most competitive at all aw values and temperatures studied, while on NaCl media P. pisce and B. halophila were usually most competitive. The Petri dish system was a useful model, but did not completely simulate the interactions observed on dried fish. Polypaecilum pisce and B. halophila were able to compete more strongly on fish than on agar media, especially at 0.90 aw. This study provides some evidence that each species examined had a niche in which it was dominant, and that species interactions as well as environmental factors are important in determining the dominant fungal species on dried salted fish. PMID- 8444647 TI - A method for multiple synchronous collection of airborne organisms and the effects on colony counts of various processing procedures. AB - A method is described for synchronous collection on agar of 10 similar specimens of airborne bacterial colony-forming units (cfu) for comparative experiments. The system delivers 50 to 100 cfu per specimen with a coefficient of variance of 13 among the 10 specimens. After collection, different methods for removing colonies from the agar surface and counting them were employed. A progressive increase in colony counts was noted when increasingly destructive procedures were used. The increases noted were 4% by wetting, 30% by jet lavage, 58% by pulsed jet lavage, 82% by blending, 130% by spreading and 340% by grinding. As airborne cfu consist mainly of skin squames with multiple organisms attached, disruption of cfu is proposed as the cause of the increases. Membrane filtration of wash fluid containing cfu from the air resulted in a 47% decrease in colony counts when compared with pour-plating. Destructive processing techniques also resulted in increased variability in colony counts. The break up of occasional exceptionally large cfu is a probable explanation. The procedure described is suitable for investigating the behaviour of airborne micro-organisms and can be modified to model surgical wound contamination by replacing the agar with tissue. PMID- 8444648 TI - An ion-exchange based extraction method for the detection of salmonellas in soil. AB - A method that uses a cation-exchange resin (Chelex 100) and differential centrifugation for the extraction and detection of salmonellas in soil was developed. The extraction efficiencies of a range of materials were examined and Chelex plus polyethylene glycol was identified as the best combination. Shake speeds, shake times and differential centrifugation speeds were selected to give an optimum salmonella recovery. The Chelex method accurately enumerated 1 cell per 10 g of nonsterile soil within 24 h. Addition of glycerol to soil samples enabled storage at -70 degrees C for 85 d without significant decreases in salmonella numbers. The Oxoid Salmonella Rapid Test (SRT) could be used to pre screen large numbers of soil samples for the presence of salmonellas, prior to analysis by the Chelex method. The SRT method detected Salmonella typhimurium at levels as low as 2.5 cells per 10 g of nonsterile soil. PMID- 8444649 TI - Microculture model studies on the effect of sorbic acid on Penicillium chrysogenum, Cladosporium cladosporioides and Ulocladium atrum at different pH levels. AB - The minimum growth-inhibitory concentration of sorbic acid has been determined for Penicillium chrysogenum, Cladosporium cladosporioides and Ulocladium atrum at pH 4.1-7.6 by using a microculture technique. This technique had earlier been applied to bacteria and Candida albicans and gave very reliable minimum inhibitory values. This investigation has shown that it is suitable also for determination of mould growth. The minimum inhibitory concentrations of sorbic acid were at the tested pH levels 1-230 mmol l-1 for P. chrysogenum, 0.3-18.0 mmol l-1 for C. cladosporioides and 0.2-33.0 mmol l-1 for U. atrum. A mathematical model for combined inhibition by dissociated and undissociated acid, which gave a good description of the minimum inhibitory concentration data earlier obtained for bacteria and Candida albicans, was suitable also for moulds. Both dissociated and undissociated acid contributed to growth inhibition. PMID- 8444650 TI - Characterization of a variant of the polysaccharide acetan produced by a mutant of Acetobacter xylinum strain CR1/4. AB - Acetobacter xylinum NRRL B42 (NCIB 40123) produces both cellulose and a complex anionic branched heteropolysaccharide called acetan. Chemical mutagenesis was used to isolate stable cellulose-minus Acetobacter xylinum mutants. Further chemical mutagenesis of these cellulose-minus A. xylinum bacteria was used to select mutants which secrete polysaccharides which are variants of the acetan structure. Preparation, purification and characterization of these polysaccharides are described. Methylation analysis of the polysaccharide structure CR1/4 suggests that the polysaccharide has an acetan structure with a truncated sidechain terminating in glucuronic acid. PMID- 8444651 TI - Effect of formulation pH and storage temperatures on the preservative efficacy of some gases used as propellants in cosmetic aerosols. AB - The effects of changes in formulation pH and storage temperature on the preservative activities of some aerosol propellants--butane, carbon dioxide, dimethylether and their combinations were investigated. A preservative challenge test method was used to determine the survival rates of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans and Aspergillus niger at formulation pH levels 5.80, 7.28 and 8.10 and storage temperatures of 20 degrees, 30 degrees and 40 degrees C. A significant decrease in the pH of formulations was observed with no corresponding changes in the antimicrobial effectiveness when carbon dioxide was incorporated. Alterations in the antimicrobial profiles of these propellants due to changes in formulation pH were dependent on the propellant and the species of the micro-organism, especially when single propellants were used. Results also showed that the propellants exert antimicrobial activities against the various organisms at the three storage temperatures but there were significantly greater inhibitory activities at 40 degrees C. With a combination of 10% butane/dimethylether (1:2) and 10 bar carbon dioxide there were no differences in the degree of microbial inhibition at the various formulation pH levels and storage temperatures. In most cases, the organisms were completely inactivated within 24 h. These findings showed that the combination of butane/dimethylether with carbon dioxide could be used to protect against microbial contamination and spoliage of formulations of different pH levels as well as those meant for storage at different temperatures. PMID- 8444652 TI - The colonization of solid PVC surfaces and the acquisition of resistance to germicides by water micro-organisms. AB - Six common water bacteria were examined for their ability to colonize polyvinyl chloride (PVC) surfaces, survive various germicidal treatment, and re-establish themselves in sterile distilled water (SDW). For each test, two 30.4 cm PVC pipes attached to a 90 degrees PVC elbow were filled with 600 ml of distilled water inoculated with either Pseudomonas aeruginosa, Ps. cepacia, Ps. mesophilica, Acinetobacter anitratus, Mycobacterium chelonae or M. chelonae var. abscessus. After 8 weeks contaminated water was removed and the pipes were exposed to 600 ml of 1:213 iodophor disinfectant (ID), 1:128 phenolic detergent (P), 1:256 quaternary ammonium compound (QA), stock iodophor antiseptic (IA), 2% formaldehyde (F), 10-15 ppm free chlorine (C), 2% glutaraldehyde (G) and 70% ethanol (E). These germicides were periodically sampled, neutralized and examined for surviving organisms. After exposure for 7 d the germicides were removed and each pipe was refilled with SDW. This was assayed at 7 d intervals to determine microbial re-establishment. Samples were removed during microbial conditioning and examined by scanning electron microscopy (SEM). Pseudomonads were isolated directly from ID, QA, C, P and F, and mycobacteria from QA, IA, ID, P, G, C and F. Pseudomonas aeruginosa and Ps. cepacia survived in PVC pipes after 7 d of exposure to P, ID and C; Ps. mesophilica, after C and ID; and both mycobacteria, after C. SEM examination of PVC remnants revealed bacterial attachment and formation of extracellular material with embedded cells. These studies show that common water bacteria can attach and colonize the interior surface of PVC pipes and develop significant resistance to the action of certain germicides.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444653 TI - The 'borderline methicillin-susceptible' Staphylococcus aureus. PMID- 8444654 TI - Synergy of cefotaxime and fosfomycin against penicillin-resistant pneumococci. AB - The killing kinetics of cefotaxime and fosfomycin, alone and in combination, against seven clinical isolates of penicillin-resistant pneumococci were studied. The antibiotics were tested at 1 x, 2 x and 4 x the MIC for each individual isolate. The results showed a synergic interaction of the two antibiotics for three of the seven strains. This strategy may be useful clinically. PMID- 8444655 TI - Effect of ampicillin versus cefuroxime on the emergence of beta-lactam resistance in faecal Enterobacter cloacae isolates from neonates. AB - Enterobacter cloacae strains dominated the aerobic faecal flora of 8.3% of 953 infants discharged from 32 Swedish neonatal intensive care units and the susceptibility of these strains to seven beta-lactam antibiotics was determined. Isolates from infants treated with cefuroxime showed slightly increased MICs only to ampicillin, cephalexin and cephalothin as compared to isolates from untreated infants matched for ward and time of sampling (P = 0.02). In contrast, E. cloacae isolates from ampicillin treated infants showed markedly elevated MICs of all agents tested including piperacillin, cefuroxime, cefotaxime and ceftazidime as compared to those from control neonates (P values between 0.001 for ampicillin and 0.017 for cefotaxime). Thus, E. cloacae with cefotaxime MICs as high as 512 mg/L were isolated only after ampicillin therapy. The resistant strains were negative in a colony DNA hybridization assay using gene probes for the plasmid beta-lactamases TEM-1, OXA-1 and SHV-1. The resistant strains also showed only one beta-lactamase band when crude cell sonicates were analysed by isoelectric focusing, and were not found in other infants in the same ward. The results indicate that the selection of chromosomal E. cloacae mutants, presumably with stably derepressed beta-lactamase production, in the faecal flora of neonates is rare during treatment with cefuroxime and more common during ampicillin therapy. PMID- 8444656 TI - Reactivity and protective capacity of a polyclonal antiserum derived from mice immunized with antibiotic exposed Escherichia coli. AB - The murine immune response to Escherichia coli O6:K-alone or pre-exposed to 0.1 x MIC of aztreonam was investigated. Relative to mice immunized with untreated bacteria, mice immunized with antibiotic-treated microorganisms presented a significantly enhanced protection towards a challenge of 100 x LD50 of viable E. coli O6:K-. Previous injection of 0.1 mL of serum drawn from mice immunized with treated and untreated bacteria protected non-immunized mice towards a challenge of 10 x LD50 of viable E. coli O6:K--. Serum from mice immunized with treated bacteria also protected non-immunized mice towards a lethal challenge of E. coli O111. The antiserum contained high titre of IgG antibodies that cross-reacted with lipopolysaccharide isolated from smooth and rough Gram-negative bacteria. Immunoblotting showed additional bands of reactivity to the untreated E. coli O6:K-. Immunization with antibiotic-treated bacteria led to the production of type specific and cross reactive antibodies that protected animals against viable homologous and heterologous lethal challenges. PMID- 8444657 TI - The in-vivo activity of co-amoxiclav with netilmicin against experimental methicillin and gentamicin resistant Staphylococcus epidermidis infection in rabbits. AB - This study compared co-amoxiclav, vancomycin and teicoplanin with and without netilmicin or amikacin for treating experimental subcutaneous fibrin-clot infection in rabbits due to a clinical beta-lactamase-positive methicillin- and gentamicin-resistant Staphylococcus epidermidis strain (MGRSE). MICs (mg/L) for this strain were: oxacillin 125, gentamicin 32, vancomycin 4, teicoplanin 8, netilmicin 1, amikacin 4, amoxycillin 64 with clavulanate at 2 mg/L. In rabbits treated with a single-dose i.v. regimen (netilmicin 8 mg/kg, amikacin 20 mg/kg, vancomycin 30 mg/kg, teicoplanin 15 mg/kg, co-amoxiclav 150-30 mg/kg), the bacterial count 24 h post-dose was reduced whatever the combination used (ANOVA, P < or = 0.001). Regimens were statistically classified in decreasing order of efficacy as follows: co-amoxiclav combined with netilmicin > vancomycin either alone or combined with either netilmicin or amikacin, teicoplanin with netilmicin > netilmicin and co-amoxiclav alone > teicoplanin or co-amoxiclav combined with amikacin, and teicoplanin alone > amikacin > no drug. From these findings, it is concluded that: co-amoxiclav could be useful for the treatment of beta-lactamase positive and methicillin-resistant S. epidermidis infection; some enzyme resistant aminoglycoside could be considered for treating gentamicin-resistant but netilmicin/amikacin-sensitive S. epidermidis infection; the combination of co amoxiclav with netilmicin was synergistic and more rapidly bactericidal than vancomycin in this animal model. PMID- 8444658 TI - Pharmacokinetics and biodistribution of methotrexate conjugated to mannosyl human serum albumin. AB - The superior efficacy of mannosylated neoglycoprotein-conjugated methotrexate, compared with free drug, in eliminating the parasite burden in both the in-vitro macrophage model and in-vivo mouse model of visceral leishmaniasis has been demonstrated previously. In the present study it was found that: (i) methotrexate conjugated to mannosyl human serum albumin (Man-HSA) was taken up rapidly by the liver and spleen, whereas the free drug was taken up by the kidney; (ii) uptake of the conjugate was ten-fold more efficient in liver macrophages (Kupffer cells) than in hepatocytes; (iii) most of the drug conjugate reached the lysosomes of Kupffer cells; and (iv) the active drug was released in the lysosomes of macrophages to act on Leishmania parasites. PMID- 8444660 TI - When is penicillin monotherapy the antibiotic treatment of choice? PMID- 8444659 TI - Efficacy and tolerance of an amphotericin B lipid (Intralipid) emulsion in the treatment of candidaemia in neutropenic patients. AB - The efficacy and tolerance of a new amphotericin B lipid emulsion (AmB-IL) in which amphotericin B was diluted in a lipid solution for parenteral nutrition (Intralipid) was assessed in fourteen episodes of candidaemia occurring in neutropenic patients. The strains isolated were Candida krusei (nine cases), Candida albicans (three cases), Candida parapsilosis (one case) and Candida lusitaniae (one case). An AmB-IL was administered at a mean dosage of 1.18 mg/kg/day (range 0.73-1.55) for 22 days (range 6-62). Flucytosine was added to AmB-IL in 12 patients (mean duration 10.6 days). Chills were noted in only 3/306 infusions of AmB-IL. A mild increase of serum creatinine level from 9.3 +/- 3 mg/L (baseline) to 10.9 +/- 3 mg/L (after completion of AmB-IL) and mild decrease of creatinine clearance from 83 +/- 28 mL/min to 56 +/- 21 mL/min were observed. These changes did not correlate with either daily or total dose of AmB-IL or length of therapy. Seven patients were cured and six improved (patients who subsequently died due to nonfungal cause) with AmB-IL. One patient died due to C. krusei pneumonia. In conclusion AmB-IL is a well-tolerated method of amphotericin B administration. It could facilitate the use of amphotericin B without impairing its efficacy for the treatment of candidaemia in neutropenic patients. PMID- 8444661 TI - Quantitative antimicrobial susceptibility testing of outer membrane-altered mutant bacteria by the E test. PMID- 8444662 TI - Determination of penicillin minimum inhibitory concentrations for Neisseria gonorrhoeae by the E test. PMID- 8444663 TI - Determination of aminoglycoside resistance mechanisms of Enterobacteriaceae isolated from a hospital in Hong Kong with antibiogram and genotyping. PMID- 8444664 TI - Inducible type of erythromycin resistance among group B streptococci isolated in Greece. PMID- 8444665 TI - Multiple antibiotic resistance in a strain of Campylobacter jejuni acquired in Jordan. PMID- 8444666 TI - Ciprofloxacin-resistant methicillin-sensitive Staphylococcus aureus. PMID- 8444667 TI - Alternative antimicrobial options against multiply resistant Staphylococcus aureus. PMID- 8444668 TI - Activity of ampicillin plus sulbactam against beta-lactamase producing enterococci in experimental endocarditis. PMID- 8444669 TI - Pharmacokinetics of once-daily amikacin in elderly patients. PMID- 8444670 TI - Clinical evaluation of teicoplanin in the treatment of gram-positive bacterial intravascular infections. PMID- 8444671 TI - Alteration in expression of Serratia marcescens porins associated with decreased outer membrane permeability. AB - The porin expression of two clinical isolates of Serratia marcescens, which overproduced cephalosporinase and had decreased outer membrane permeability, were studied in comparison with those of reference strains. Separation of the porin proteins assessed by SDS-PAGE containing urea revealed that both clinical isolates overexpressed a single porin of 44 and 43 kilodalton (kDa), respectively. In contrast, the in-vitro porin deficient mutant, which was derived from the reference strain IFO3736 as latamoxef-resistant, showed decreased outer membrane permeability, but produced low levels of all three peptidoglycan associated porins of 45, 44 and 43 kDa, and overexpressed 39 kDa OmpA protein. These observations suggested that the clinical isolates had a different mechanism of latamoxef resistance compared with the mutant and overexpressed possible narrow transport channels of 44 or 43 kDa. The 45 kDa porin may facilitate a more effective channel than the other two proteins. Heterogeneity of porin profiles between biotypes was also suggested. The two isolates were also resistant to penicillins and cephalosporins tested, but imipenem was the most active agent and inhibited the isolates at 1.56 mg/L. PMID- 8444672 TI - A survey of beta-lactamases from 618 isolates of Klebsiella spp. AB - beta-Lactamases from 618 isolates of Klebsiella spp. (487 Klebsiella pneumoniae and 131 Klebsiella oxytoca) were identified by analytical isoelectric focusing. The strains were consecutive isolates from 618 different patients in five hospital centres between 1980 and 1984. Most of the chromosomal beta-lactamases from the K. pneumoniae isolates had a pI of 7.1, and most of the K. oxytoca isolates had chromosomal beta-lactamases of pIs 7.8, 5.3 and 5.5. Plasmid mediated beta-lactamases were produced by 91.8% of K. pneumoniae isolates and 9.9% of K. oxytoca isolates. The beta-lactamase types identified most frequently were SHV-1 in the former species, and TEM-1 in the latter species. Of the K. pneumoniae isolates, 101 produced both of these plasmid-mediated beta-lactamases, while one strain produced an extended-spectrum SHV-like beta-lactamase. Of the 131 K. oxytoca isolates, 20 were hyper-producers of chromosomal beta-lactamase. The susceptibility of this genus to beta-lactam antibiotics is controlled almost exclusively by beta-lactamases, the production of which may differ from one strain to another; thus the empirical therapeutic use of beta-lactam antibiotics is not recommended for this genus. PMID- 8444673 TI - Influence of sub-inhibitory concentrations of antibacterials on the surface properties and adhesion of Escherichia coli. AB - The effect of sub-inhibitory concentrations of antibacterials, including quinolones, on the surface properties of a uropathogenic strain of Escherichia coli was examined. The effect on the charge and hydrophobicity of the cell surface was assessed by means of partition between two aqueous phases, polyethylene glycol and dextran. Antibiotics at 1/8 x MIC inhibited adhesion to uroepithelial cells, and induced an increase in bacterial charge and hydrophobicity. Inhibition of adhesion correlated with increased charge, but not with hydrophobicity. The influence of magnesium on the inhibition of adhesion by sub-MICs of pefloxacin was also investigated. Loss of the anti-adhesive property of pefloxacin was observed with increasing magnesium concentrations, suggesting that quinolones should be free from magnesium to induce an inhibition of adhesion. Examination by electron microscopy showed a disappearance of fimbriae following treatment of E. coli cells with 1/8 x MIC of pefloxacin. PMID- 8444674 TI - Effect of divalent cations in bacteriological media on the susceptibility of Xanthomonas maltophilia to imipenem, with special reference to zinc ions. AB - The susceptibility of Xanthomonas maltophilia strains to beta-lactams is known to vary according to the type of growth media used. We have assayed the divalent cation content of various susceptibility testing media and correlated this with the susceptibility to imipenem of 30 strains of X. maltophilia, by calculating the IC50. No correlation was found with Ca++ and Mg++ content (r = 0.005, P = 0.99), but a highly significant correlation with the Zn++ content (7.7-42.7 mumol/L) of the medium was found (r = 0.93, P = 0.003). The effect of Zn++ on the susceptibility of X. maltophilia to imipenem was further investigated by adding varying amounts of zinc sulphate to Oxoid Mueller-Hinton agar which has a low Zn++ content (14.2 mumol/L). A highly significant correlation between the Zn++ content and the IC50 was observed (r = 0.95, P = 0.001). Some variability was seen from one series of IC50 determinations to another and samples of ultra-pure water were processed in exactly the same fashion as the agar media and then assayed for cation content. No significant increase in Ca++ or Mg++ content of the water were observed but water autoclaved in universal containers with metal caps and rubber washers acquired up to 40 mumol/L of Zn++. Studies of the correlation between in-vitro sensitivity tests and the clinical performance of beta-lactams used against X. maltophilia will need to take account of the Zn++ content of the susceptibility testing media used. PMID- 8444675 TI - Impact of different statistical methodologies on the evaluation of the in-vitro MICs for Bacteroides fragilis of selected cephalosporins and cephamycins. AB - The purpose of this study was to assess the effect of different MIC statistics on the in-vitro evaluation of cefoxitin, cefotetan, ceftizoxime, cefotaxime, desacetylcefotaxime, and cefotaxime:desacetylcefotaxime (1:1 ratio) against clinical isolates of Bacteroides fragilis from the Medical University of South Carolina. MICs were determined by the agar dilution method following NCCLS guidelines. Statistical analyses included arithmetic and geometric means, median, mode, MIC50, MIC90, and range. Differences between antimicrobial agents were determined using parametric and nonparametric methods. Consistent with previous in-vitro studies on anaerobes with these agents, a wide range in the MICs was observed. The arithmetic mean MIC was lowest for cefotetan, but the geometric mean MIC was lowest for ceftizoxime. Using the MIC90, cefotetan was at least a two-fold dilution more active than the other agents. After natural logarithmic transformation of the MIC data, analysis of variance with the Scheffe post-hoc test demonstrated that the MICs of ceftizoxime were significantly lower than those of cefoxitin (P < 0.001), cefotetan (P < 0.05), cefotaxime (P < 0.05), and desacetylcefotaxime (P < 0.001). Median and mode MICs were lowest for ceftizoxime and cefotaxime:desacetylcefotaxime. Using published breakpoints, cumulative percent susceptibility was similar for all agents studied. In this analysis of the antimicrobial susceptibility of B. fragilis in our institution, the in-vitro activity of the cephalosporins and cephamycins tested appeared to be very similar when all statistical data were evaluated. Since apparent in-vitro activity may be influenced by the statistic evaluated, we suggest that all MIC data be reported to allow for a more complete analysis of microbiological potency. PMID- 8444676 TI - The E test for antimicrobial susceptibility testing of Helicobacter pylori. AB - Antimicrobial susceptibility testing of Helicobacter pylori by conventional means (disc diffusion) is of questionable value because the bacterium grows so slowly. We have determined the susceptibilities of 20 isolates of H. pylori to ampicillin, erythromycin, gentamicin, metronidazole, rifampicin and tetracycline by the E test, a novel technique for measuring MICs, and compared the results with those determined by standard agar dilution and disc diffusion methods. Eighty-one per cent of E test-determined MICs were within one two-fold dilution and 93% were within two two-fold dilutions of those determined by the reference agar dilution method. MICs determined by the E test were highly reproducible; replicate results were invariably within one two-fold dilution. MICs were not affected by the size of the inoculum, preincubation or incubation times. Regression lines for disc diffusion could not be determined because of the lack of resistant strains. However, metronidazole-resistant strains (MIC > 32 mg/L) were easily distinguishable from susceptible strains (MIC < 1 mg/L). In conclusion, the E test is a reliable method for determining the antimicrobial susceptibility of H. pylori. PMID- 8444677 TI - RO 23-9424, a new cephalosporin 3'-quinolone: in-vitro antimicrobial activity and tentative disc diffusion interpretive criteria. AB - The susceptibility of 410 clinical bacterial isolates to RO 23-9424, a novel cephalosporin 3'-quinolone, was determined. Overall, 97% of Enterobacteriaceae and 100% of staphylococci were inhibited by < or = 8.0 mg/L of RO 23-9424. Only 60% of Pseudomonas aeruginosa and 80-90% of Pseudomonas spp. and Xanthomonas maltophilia were inhibited by this concentration. Enterococci and Listeria monocytogenes were resistant to RO 23-9424. Clinical isolates of Moraxella catarrhalis, Streptococcus spp., and Corynebacterium jekeium were all susceptible to < or = 8.0 mg/L of RO 23-9424. This drug's antimicrobial activity was superior to that of its two components fleroxacin and desacetylcefotaxime against the organisms tested. Using < or = 8.0 mg/L and > or = 32 mg/L respectively as the susceptible and resistant MIC breakpoints for RO 23-9424, the regression analysis derived disc diffusion zone diameter breakpoints for the 30 micrograms disc are: susceptible > or = 19 mm, intermediate 16-18 mm, and resistant < or = 15 mm. PMID- 8444678 TI - Nitroimidazole drugs--action and resistance mechanisms. I. Mechanisms of action. PMID- 8444679 TI - Electrolyte and fluid transport across the mature alveolar epithelium. AB - The lungs must be kept "dry" for efficient gas exchange. The mechanisms that contribute to clear alveoli from fetal lung fluid at birth are still present during adult life and allow recovery from alveolar flooding. It has recently been shown with the use of different approaches in vitro, as well as in vivo, that alveolar epithelium performs solute-coupled fluid transport. Fluid absorption from alveoli occurs chiefly as a result of active transepithelial Na+ transport. The mechanisms of Na+ transport have been partly elucidated; Na+ enters alveolar cells through apical Na+ channels and Na(+)-coupled solute transporters and is pumped out at the basolateral membrane by a Na(+)-K(+)-adenosinetriphosphatase (ATPase). Transepithelial Na+ transport and fluid absorption are stimulated by beta-adrenergic agonists, with adenosine 3',5'-cyclic monophosphate being the likely intracellular second messenger. K+ is probably secreted into alveoli because its concentration in the epithelial lining fluid is larger than expected for passive distribution. K+ channels have been described that, in conjunction with Na(+)-K(+)-ATP-ase, might provide pathways for active transport. Active proton secretion or bicarbonate absorption have been reported, which may explain the low pH of the alveolar epithelial lining fluid. It is probable that active solute transports are the main determinants of epithelial lining fluid depth and composition. A challenge for the future is to understand how this homeostasis is achieved. PMID- 8444681 TI - Interaction of oscillatory and steady turbulent flows in airway tubes during impedance measurement. AB - Measurement of input respiratory impedance is carried out by superimposing forced oscillations on spontaneous breathing. The latter thus acts as a quasi-steady unidirectional flow component, with effects on the measured impedance that are habitually neglected (linearity assumption). We examined the validity of that assumption in the case of a turbulent steady flow. We tested the validity of a fluid dynamics criterion previously proposed in water channel experiments for gas flow in a tube. This criterion states that oscillatory and continuous turbulent flow may or may not interact if the Stokes boundary layer (ls) is embedded within the viscous sublayer (lv), i.e., if lS+ = lS/lv < or = 10, implying Re7/8 < or = (100 alpha/square root of 2), for a fully developed hydraulically smooth turbulent flow in a tube (where alpha is Womersley parameter and Re is Reynolds number of the steady-flow component). Experiments were performed in long rigid circular and semicircular tubes by superimposing two independent well-defined flows: 1) laminar oscillatory flow obeying the linear transmission line model (frequency = 1.5-250 Hz, i.e., alpha = 6-80) and 2) fully developed turbulent flow characterized by Blasius resistance formula (Re = 3,000-16,000). Confirming the validity of the criterion above, we found that the real and the imaginary parts of the long-tube impedance did not differ from those measured in the absence of a steady-flow component, provided lS+ < or = 10. On the contrary, the real parts measured with and without the continuous component differed greatly as soon as lS+ > 10, both for circular and semicircular tubes and for outward as well as inward steady flows. We concluded that the proposed criterion is pertinent for predicting appropriate oscillation frequency for a given rate of spontaneous flow, such that oscillatory and turbulent flows do not interact. Application of the forced oscillation measurement technique during spontaneous breathing requires use of a range of oscillatory frequencies higher than the frequency range classically used during apnea. PMID- 8444680 TI - Stimulation of vagal afferents inhibits locomotion in mesencephalic cats. AB - Using electrical stimulation of the mesencephalic locomotor region, we made decerebrate unanesthetized cats walk on a treadmill. The locomotion induced by stimulation of this midbrain area was assessed before and during activation of vagal afferents by either intravenous injection of phenylbiguanide or inflation of a balloon placed in the left atrium. Inflation of a balloon, which increased left atrial pressure by 7-25 mmHg, abolished locomotion in 9 of 10 cats tested. Bilateral cervical vagotomy prevented the abolition of locomotion by balloon inflation in each of two cats tested. Intravenous phenylbiguanide (50 or 100 micrograms/kg) or serotonin (40 micrograms/kg) injections abolished or attenuated walking induced by midbrain stimulation in 11 of 13 cats tested. In addition, intravenous phenylbiguanide injections abolished or attenuated locomotion with a shorter onset time than did systemic injections of this substance in five of six cats tested. Bilateral cervical vagotomy prevented the abolition of locomotion by phenylbiguanide injection in each of five cats tested. We conclude that locomotion can be prevented by a viscerosomatic reflex arising from the lungs and heart. The afferent arm of this reflex arc is the vagus nerve. Afferents such as slowly and rapidly adapting pulmonary stretch receptors, atrial receptors, and lung C-fibers may have had a role in preventing locomotion during the increase in left atrial pressure in our experiments. On the other hand, pulmonary C-fibers had a crucial role in preventing locomotion during intravenous injection of phenyl-biguanide. We speculate that this viscerosomatic reflex may help to explain in part the intolerance for exercise displayed by patients with congestive heart failure. PMID- 8444682 TI - Edema clearance in isolated sheep lungs. AB - Edema may be cleared from the lung by lymphatic drainage, transudation across the visceral pleural, vascular reabsorption, and movement into the mediastinum. To determine the quantity and mechanisms of edema clearance associated with spontaneous edema formation in isolated sheep lungs, we perfused six lungs for 180 min with blood (100 ml.kg-1.min-1) at subatmospheric left atrial pressure (Pla) from a weighed reservoir. In six other lungs, Pla was increased to 20 mmHg at 30-75 min to further augment edema. Fluid drainage from the lung was fractionated into blood and water components by serial measurements of drainage and perfusate hematocrit. Changes in weight of circulating intravascular blood and extravascular lung water (EVLW) were also directly measured by dye dilution and standard gravimetric techniques, respectively. From these measurements, we calculated that 3.04 +/- 0.53 g/g blood-free dry lung of water filtered into the extravascular space during perfusion. Of this amount, 42% was reabsorbed into the pulmonary vasculature; 18% drained from the lung via lymphatics, visceral pleura, and mediastinum; and 40% was retained in the lung. Compared with low Pla lungs, transient elevation of Pla increased lung hemorrhage and the final change in reservoir weight, but the quantity and clearance of cumulative filtered water and the final values of EVLW and wet-to-dry weight ratio (WW/DW) were not altered. These results suggest that 1) significant edema clearance occurred in isolated sheep lungs, primarily by vascular reabsorption, and 2) measurements of EVLW and WW/DW under-estimated injury in the presence of lung hemorrhage and significant edema clearance. PMID- 8444683 TI - Endogenous substrate oxidation during exercise and variations in breath 13CO2/12CO2. AB - This study attempted to induce a major shift in the utilization of endogenous substrates during exercise in men by the use of a potent inhibitor of adipose tissue lipolysis, Acipimox, and to see to what extent this affects the 13C/12C ratio in expired air CO2. Six healthy volunteers exercised for 3 h on a treadmill at approximately 45% of their maximum O2 uptake, 75 min after having ingested either a placebo or 250 mg Acipimox. The rise in plasma free fatty acids and glycerol was almost totally prevented by Acipimox, and no significant rise in the utilization of lipids, evaluated by indirect calorimetry, was observed. Total carbohydrate oxidation averaged 128 +/- 17 (placebo) and 182 +/- 21 g/3 h (Acipimox). Conversely, total lipid oxidation was 84 +/- 5 (placebo) and 57 +/- 6 g/3 h (Acipimox; P < 0.01). Under placebo, changes in expired air CO2 delta 13C were minimal, with only a 0.49/1000 significant rise at 30 min. In contrast, under Acipimox, the rise in expired air CO2 delta 13C averaged 1/1000 and was significant throughout the 3-h exercise bout; in these conditions calculation of a "pseudooxidation" of an exogenous sugar naturally or artificially enriched in 13C, but not ingested, would have given an erroneous value of 19.8 +/- 2.6 g/3 h. Thus under conditions of extreme changes in endogenous substrate utilization, an appropriate control experiment is mandatory when studying exogenous substrate oxidation by 13C-labeled substrates and isotope-ratio mass spectrometry measurements on expired air CO2. PMID- 8444684 TI - Species differences in pulmonary vasoactive responses to histamine, 5 hydroxytryptamine, and KCl. AB - Species differences in the longitudinal distribution of pulmonary vascular resistance (PVR) in response to 5-hydroxytryptamine (5-HT) or histamine (His) may be attributed to variations in the distribution of functional smooth muscle between arteries and veins estimated by the response to KCl. Isolated dog, guinea pig, or rabbit lungs were perfused at a constant flow = 55-75 ml.min-1.kg body wt 1. Pulmonary arterial (Ppa); arterial, double, and venous occlusion (Po,a; Pdo; Po,v, respectively); and pulmonary venous (Ppv) pressures were measured before and after increasing PVR by infusing His, 5-HT, or KCl. 5-HT and His increased Ppa--Pdo in rabbits but Pdo--Ppv in guinea pigs. In dogs, 5-HT increased Ppa- Po,a, but His increased Pdo--Ppv. Dynamic (Co,v) and static vascular compliance (CP-Q), as well as critical closing pressure (Pcc, the gamma-intercept of pressure-flow curves), were also measured. At baseline, Co,v was the same among species. However, CP-Q was higher than Co,v in all lungs and was significantly different among species in order of (in ml.cmH2O-1.100 g-1) rabbit (4.54 +/- 0.28) > guinea pig (3.31 +/- 0.18) > dog (2.21 +/- 0.13). Increases in Pcc correlated with increases in microvascular resistance (Po,a--Po,v) but not with increases in PVR after agonist infusion. KCl responses suggest that guinea pigs and rabbits have relatively more functional smooth muscle in venous and arterial microvessels, respectively, whereas dogs have approximately equal amounts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444685 TI - Regional blood flow during closed-chest cardiac resuscitation in rats. AB - Quantitative measurement of regional blood flow during cardiac arrest and resuscitation has been confined to large animals. We report on a rodent model utilizing radioactive microspheres during cardiac arrest and resuscitation for investigation of regional blood flow. Ventricular fibrillation was electrically induced in 10 pentobarbital-anesthetized Sprague-Dawley rats. Resuscitation was attempted by precordial compression followed by external direct current countershock. During precordial compression, cardiac output corresponded to 12% of prearrest flow. Similarly low flows were observed in the myocardium and brain. However, much lower flows were observed in the adrenal glands, kidneys, intra abdominal viscera, skin, and skeletal muscle. Five of ten animals were successfully resuscitated. During precordial compression, resuscitated animals had significantly higher cardiac output (13.1 +/- 4.1 vs. 8.6 +/- 1.46 ml/min), myocardial blood flow (0.70 +/- 0.24 vs. 0.22 +/- 0.15 ml.min-1.g-1), cerebral blood flow (0.17 +/- 0.04 vs. 0.06 +/- 0.02 ml.min-1.g-1), and adrenal blood flow (1.09 +/- 0.60 vs. 0.27 +/- 0.16 ml.min-1.g-1). Thirty minutes after successful resuscitation, cardiac output and myocardial, cerebral, renal, and adrenal blood flows and blood flow to splanchnic viscera (with the exception of the spleen) had returned to > or = 70% of prearrest flows. These studies confirm the conclusion of earlier investigations in larger animals that visceral blood flow during cardiac arrest and precordial compression is preferentially distributed to the brain and myocardium. Successful cardiac resuscitation is contingent on threshold levels of myocardial blood flow that exceed 0.4 ml.min-1.g-1. PMID- 8444686 TI - Hypoproteinemia slows lung liquid clearance in young lambs. AB - To determine whether hypoproteinemia slows the rate at which liquid is cleared from the lung lumen, we studied 36 lambs, 18 of which underwent repeated plasmapheresis, reducing plasma protein concentration by 37% and plasma protein osmotic pressure by 39%. We killed 29 lambs (14 hypoproteinemic and 15 normoproteinemic) and removed their lungs 1, 2, or 6 h after intratracheal instillation of isotonic saline (6 ml/kg body wt). We measured extravascular lung water and determined the percentage of tracheally instilled liquid that was cleared from the lungs by comparison with control lambs that did not receive saline into their airways. The percent liquid cleared from the lungs after 1 and 2 h was significantly less in hypoproteinemic than in normoproteinemic lambs (37 vs. 65% at 1 h, 58 vs. 75% at 2 h, respectively). By 6 h nearly all the liquid (> 92%) was cleared from the lungs of all lambs. Thus hypoproteinemia slows the initial rate of clearance of liquid from the lungs of lambs. To determine whether reduced plasma protein osmotic pressure might redirect this liquid into lung lymphatics, we measured lung lymph flow (Q1) in five lambs (7.7 +/- 1.4 kg, 19 +/ 4 days old) for > or = 2 h before and 6 h after tracheal instillation of saline. In each lamb, paired studies were done 3-6 days apart; between studies the lambs underwent plasmapheresis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444687 TI - Abdominal muscle activation by respiratory stimuli in conscious dogs. AB - The responses of the diaphragm, external oblique, and transversus abdominis muscles to hyperoxic hypercapnia and isocapnic hypoxia were studied in four awake dogs to test the hypothesis that central and peripheral chemoreceptor inputs result in different patterns of respiratory muscle activation. The dogs were trained to lie quietly in place, and electromyographic (EMG) discharges of the diaphragm (EMGdi), external oblique (EMGeo), and transversus abdominis (EMGta) were recorded from chronically implanted electrodes. Both hypercapnia and hypoxia recruited EMGeo and EMGta activity, but at comparable levels of minute volume of ventilation the EMG activity of the abdominal muscles was greater during hypercapnia than during hypoxia. However the two chemical stimuli also resulted in different tidal volume (VT) and respiratory frequency responses at any given minute volume of ventilation. When EMG activity was reanalyzed as a function of VT, EMGeo and EMGta were the same for a given VT whether induced by hypercapnia or hypoxia, but EMGdi was consistently greater during hypoxia than during hypercapnia. When the vagus nerves were blocked by cooling exteriorized cervical vagal loops, all abdominal muscle EMG activity was abolished. The findings support the concept that stimulation of the central and peripheral chemoreceptors results in asymmetric activation of the inspiratory and expiratory respiratory muscles. The findings also indicate that afferent vagal stimuli play an important facilitatory role in activation of the abdominal expiratory muscles. PMID- 8444688 TI - Pulmonary impedance and right ventricular-vascular coupling during coronary angioplasty. AB - Right ventricular ejection may be modified by alterations in pulmonary vascular properties during acute pulmonary hypertension. Pulmonary artery impedance and reflection properties were analyzed during coronary angioplasty in nine patients with single-vessel disease involving the left anterior descending artery by use of high-fidelity catheter recordings of pulmonary pressure and flow made before angioplasty balloon inflation and at peak ischemia. Acute pulmonary hypertension in this resting model resulted in a significant decrease in pulmonary vascular resistance (142 +/- 54 to 92 +/- 64 dyn.s.cm-5, P < 0.05), increase in low frequency impedance (67 +/- 36 to 101 +/- 43 dyn.s.cm-5, P < 0.05), and no change in high-frequency (characteristic) impedance (38 +/- 14 to 41 +/- 13 dyn.s.cm-5). Pulmonary wave reflection amplitudes were increased, and the amount of hydraulic power expended per unit of net forward flow significantly increased (3.1 +/- 0.7 to 4.3 +/- 0.7 mW.ml-1.s-1, P < 0.001). These findings indicate that, during acute pulmonary hypertension in humans, 1) recruitment of additional resistance vessels can occur, 2) pulsatile pulmonary artery properties are significantly altered, and 3) right ventricular power output requirements are increased. Because episodic pulmonary hypertension occurs frequently in coronary artery disease, these changes may help explain eventual right ventricular hypertrophy or failure. PMID- 8444689 TI - Behavior of coactive muscles during fatigue. AB - Coactivation is antagonist muscle activity that occurs during voluntary contraction. Recently, we showed that the extent of coactivity in the knee flexors decreases after a short period of resistance training of the knee extensors (8). The purpose of the present experiment was to study the time course of coactivation in the knee flexors during fatigue of the knee extensors. Ten male subjects performed repeated submaximal static leg extensions in a low intensity long-duration and a high-intensity short-duration fatigue protocol until they could no longer produce the required force [time limit of endurance (Tlim)]. Maximal voluntary contraction (MVC), submaximal force, and surface electromyographic (EMG) activity were measured periodically. Vastus lateralis EMG increased progressively during fatigue of the extensor muscles (P < 0.05), resulting in a 38% change from control at Tlim. Biceps femoris EMG, which was our measure of coactivation, also increased by approximately 60% at Tlim in each protocol (P < 0.05). These observations lead us to conclude that a small but significant force loss during repeated static contractions to Tlim is due to an increase in antagonist activity. Moreover, the close correlation between the antagonist and agonist EMG supports the notion of a "common drive" to both motoneuron pools (10). PMID- 8444690 TI - Effects of reduced O2 delivery with anemia, hypoxia, or ischemia on peak VO2 and force in skeletal muscle. AB - This investigation was designed to describe alterations in O2 uptake (VO2) and tension development in a contracting in situ gastrocnemious-plantaris muscle preparation during three conditions of reduced O2 delivery [arterial O2 concentration X blood flow (Q)]. The three conditions, hypoxemia (H), ischemia (I), and anemia (A), were matched for O2 delivery. A normoxic normal flow condition was also utilized for comparison. H was produced by respiring the animals with 9% O2 in N2; I was produced by lowering Q, and A was produced by hemodilution with 6% dextran. The stimulation pattern for the isometric tetanic contractions used was 1 train/s, and each train was 200 ms, 70 Hz, and 6 V. The muscle was maximally contracted during each of the experimental conditions, and the conditions were administered in random order. In each bout the contractions continued for 5 min with 30 min of rest between bouts. Samples of arterial and muscle venous blood were obtained during the last 30 s of each bout. VO2 during I (125 ml.kg-1.min-1) was less than during N (145 ml.kg-1.min-1; P < 0.05) and greater than during H or A (104 and 101 ml.kg-1.min-1, respectively; P < 0.05). Venous PO2 (PVO2) was significantly lower during H (17.1 Torr) compared with the other conditions; no differences existed between N, I, and A (26.8, 26.0, and 28.1 Torr, respectively). Tension development was reduced by the reduction of O2 delivery during I, H, and A compared with N. Tension developed among the reduced O2 delivery groups was not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444691 TI - Lung volume, pressure, flow, and density relationships during constant-flow ventilation in dogs. AB - Lung volume changes during constant-flow ventilation (CFV) using cannulas in the main stem bronchi were examined in six beagle dogs. The increase in lung volume was found to depend mainly on the outflow resistance to gas flow in the trachea and tracheal tube. The resistance changed with gas flow, indicating that gas flow was transitional between laminar and turbulent flow (resistance varies; is directly proportional to flow1.5). There was a small pressure gradient between trachea and alveoli (1.1-1.3 cmH2O) that was independent of flow rate or gas velocity out of the CFV cannulas. This was attributed to momentum transfer from the gas jet from the CFV cannulas modified by friction between the gas jet and the airway wall. PMID- 8444692 TI - Regional blood flow in conscious resting rats determined by microsphere distribution. AB - To determine organ blood flow in the resting state, a box was designed to keep conscious untrained rats minimally disturbed. Blood pressure, heart rate, and organ blood flow, determined by the microsphere distribution and reference sampling technique, were measured in 11 Sprague-Dawley rats. After an acclimation period, 15-microns-diameter microspheres labeled with 113Sn were infused into the ascending aorta, a reference blood sample was withdrawn from the caudal artery, and organ blood flows were computed according to standard procedures. The average values of heart rate (365 beats/min) and blood flow to the brain (45 ml.min-1.100 g-1) and hindlimb muscles (15 ml.min-1.100 g-1) were significantly lower than most values reported earlier, whereas splanchnic blood flow was significantly higher (106 ml.min-1.100 g-1). Blood flow to the soleus muscle, which is considered the most active for postural maintenance, was relatively high (99 ml.min-1.100 g-1). The combination of low skeletal muscle and high visceral blood flows observed in these experiments suggests a low sympathetic tone, which is consistent with the low level of circulating catecholamines also observed in this study. It is hypothesized that the difference between our present and previous results is a lower level of stress, attributable to a more complete acclimation to the experimental environment. PMID- 8444693 TI - Changes in regional blood flow distribution and oxygen supply during hypoxia in conscious rats. AB - The effects of acute hypoxia on central hemodynamics, regional blood flow, and regional oxygen supply (blood flow x arterial O2 concentration) were studied in conscious resting rats. Regional blood flow was determined by the radiolabeled microsphere technique. Blood pressure, heart rate; and aortic blood flow increased and total peripheral resistance decreased significantly during hypoxia. Blood flow to brain, respiratory muscles, and liver increased both in absolute value and as a fraction of the aortic blood flow. Fractional blood flow to the gastrointestinal tract, spleen, pancreas, skin, fat, and hindlimb bones decreased during hypoxia; blood flow decreased in absolute values only in stomach and fat. Oxygen supply to brain, respiratory muscles, and liver increased during hypoxia, whereas it decreased in the remaining organs investigated. PMID- 8444694 TI - Influence of signal processing on estimation of respiratory impedance. AB - Respiratory impedance was estimated between 4 and 30 Hz by spectral analysis of the mouth flow and pressure signals measured in spontaneously breathing subjects when applying a pseudorandom pressure excitation at the mouth. The signals were submitted to antialiasing low-pass filtering followed by digital preprocessing before the calculation of spectra by a fast Fourier transform algorithm. The effectiveness of signal preprocessing in eliminating the leakage error due to breathing noise was illustrated in both a mechanical analogue and a patient. Five preprocessing techniques that combined high-pass filtering and windowing were then compared in 32 randomly selected patients by examining the influence of these techniques on 1) the values of impedance at 5, 10, and 20 Hz, and 2) the parameters of linear models fitting the real (Zr) and imaginary (Zi) parts of impedance for coherence values higher than a preset threshold. The impedance values and derived parameters were either the mean of the estimates separately obtained in the three data recordings (PA) or the single estimate obtained from average spectra (SP). Small but significant differences between filtering and windowing, as well as between SP and PA, were evidenced for the Zr, whereas Zi was only slightly sensitive to the type of averaging technique. We conclude that the signal preprocessing and data averaging techniques selected in this study have similar effects on spectral estimation of respiratory impedance. PMID- 8444695 TI - Thromboxane contributes to pulmonary hypertension in ischemia-reperfusion lung injury. AB - Exposure of isolated perfused rabbit lungs (IPL) to ischemia-reperfusion causes a transient increase in pulmonary arterial (PA) pressure at the onset of reperfusion. Because thromboxane A2 (TxA2) is a potent vasoconstrictor, we hypothesized that it may contribute to the ischemia-reperfusion-induced pressor response. To evaluate this hypothesis, we exposed IPL perfused with a cell-free solution to 40 min of warm ischemia followed by reperfusion and measured perfusate immunoreactive thromboxane B2 (iTxB2) and 6-ketoprostaglandin F1 alpha (i6-keto-PGF1 alpha). We observed that ischemia-reperfusion IPL compared with controls had an increase in PA pressure (40.2 +/- 4.8 vs. 9.3 +/- 0.3 mmHg, P < 0.05), lung edema (29.3 +/- 6.3 vs. -0.2 +/- 0.2 g, P < 0.05), iTxB2 perfusate levels (155 +/- 22 vs. < 50 pg/ml, P < 0.05), and i6-keto-PGF1 alpha (436 +/- 33 vs. 61 +/- 16 pg/ml, P < 0.05). In ischemia-reperfusion IPL, infusion of SQ 29548 (10(-6) M), a specific TxA2/prostaglandin H2 receptor antagonist, attenuated the PA pressor response and the degree of edema. We conclude that pulmonary hypertension associated with ischemia-reperfusion results in part from pulmonary release of TxA2. Furthermore, TxA2 directly through membrane effects or indirectly through hydrostatic mechanisms increases the severity of ischemia reperfusion-induced lung edema. PMID- 8444696 TI - Effects of acute and chronic acetazolamide on resting ventilation and ventilatory responses in men. AB - The effects of acetazolamide (ACTZ) on ventilatory control are thought to be mediated by metabolic acidosis. However, carbonic anhydrase (CA) inhibition within brain and chemoreceptors and tissue respiratory acidosis may also be important. We compared the acute effects of ACTZ (tissue respiratory acidosis and tissue CA inhibition without metabolic acidosis) on ventilation and ventilatory control with chronic ACTZ (acute effects plus metabolic acidosis). Five men were studied 1 h after 500 mg iv ACTZ or 0.9% saline (acute effects) and also after three doses of ACTZ (500 mg po every 6 h; chronic effects). Minute ventilation (VE), steady-state hypercapnic ventilatory response (HCVR), and hypoxic ventilatory response (HVR) were measured with respiratory inductance plethysmography. Resting VE was increased equally by acute and chronic ACTZ. HCVR increased with chronic ACTZ in hyperoxia and even further in hypoxia. In contrast, acute ACTZ had no effect on the HCVR slope in hyperoxia and suppressed its augmentation by hypoxia. HVR was fully suppressed by acute ACTZ but unchanged with chronic ACTZ. ACTZ also slowed the rate of full ventilatory response to CO2. These findings show that CA inhibitors affect ventilatory control in a complex fashion, not only through changes in systemic acid-base balance but also by central and peripheral chemoreceptor inhibition. PMID- 8444697 TI - Functional significance of expiratory muscles during spontaneous breathing in anesthetized dogs. AB - Recent electromyographic studies in awake and anesthetized dogs have demonstrated that spontaneous breathing in prone dogs is associated with an increased activation of the expiratory muscles compared with that recorded in supine dogs. On the basis of these observations, one would infer that the mechanical role and contribution of the expiratory musculature to the act of breathing are enhanced in the prone posture. The changes in length associated with these postural increases in expiratory muscle electrical activity, however, have not been investigated and formed the basis of our investigation. We examined the active and passive changes in length of expiratory muscles during spontaneous breathing in supine and prone anesthetized dogs and assessed the relative role of the expiratory musculature in the generation of tidal volume. The experiments were performed on eight mongrel dogs anesthetized with pentobarbital sodium. In all eight animals, spontaneous breathing in the prone posture was associated with an increased activation (electromyogram) of the triangularis sterni, external oblique, and transversus abdominis muscles compared with that recorded in the supine posture. We quantitated the role of the expiratory muscles in both postures by measuring the volume difference between relaxation volume of the respiratory system and the end-expiratory lung volume. In the supine animal, 93 ml were attributed to the expiratory musculature, whereas in the prone animal, we noted that 186 ml (P < 0.01) were displaced during expiration, representing 43 and 52% (NS) of tidal volume, respectively. During spontaneous breathing in the supine or prone posture, all three expiratory muscles underwent significant length changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444698 TI - Cooling the pulmonary blood in dogs alters activity of pulmonary vagal afferents. AB - In open-chest anesthetized dogs with left and right lungs ventilated separately, we recorded changes in firing of right lung vagal receptors when 1.25 ml/kg cold (5 degrees C, 20 degrees C) blood were injected into the nonperfused right pulmonary artery. With the right lung inflated at constant pressure, effects of cold blood on individual pulmonary stretch receptors (PSRs) were frequency dependent, with discharge increasing or remaining unchanged if control frequency was low and decreasing if it was high. Consequently average PSR discharge was unchanged by cold blood when airway pressure was maintained at 5 cmH2O, but it decreased at pressures of 10 and 15 cmH2O. Cold blood stimulated rapidly adapting receptors (RARs) at all three pressures. Injection of blood at 37 degrees C had no effect. We conclude that changes in PSR activity account for the tachypnea induced by pulmonary arterial injection of cold blood (G. G. Giesbrecht and M. Younes. J. Appl. Physiol. 69: 1435-1441, 1990). With the right lung phasically ventilated, cold blood decreased PSR discharge in inflation, caused high threshold PSRs to fire in deflation, and stimulated RARs. Pulmonary C-fibers were unaffected by cold blood. We suggest that PSRs and RARs initiate respiratory changes during hypothermia or exercise-induced asthma. PMID- 8444699 TI - Middle cerebral artery blood velocity and cerebral blood flow and O2 uptake during dynamic exercise. AB - Results obtained by the 133Xe clearance method with external detectors and by transcranial Doppler sonography (TCD) suggest that dynamic exercise causes an increase of global average cerebral blood flow (CBF). These data are contradicted by earlier data obtained during less-well-defined conditions. To investigate this controversy, we applied the Kety-Schmidt technique to measure the global average levels of CBF and cerebral metabolic rate of oxygen (CMRO2) during rest and dynamic exercise. Simultaneously with the determination of CBF and CMRO2, we used TCD to determine mean maximal flow velocity in the middle cerebral artery (MCA Vmean). For values of CBF and MCA Vmean a correction for an observed small drop in arterial PCO2 was carried out. Baseline values for global CBF and CMRO2 were 50.7 and 3.63 ml.100 g-1.min-1, respectively. The same values were found during dynamic exercise, whereas a 22% (P < 0.0001) increase in MCA Vmean was observed. Hence, the exercise-induced increase in MCA Vmean is not a reflection of a proportional increase in CBF. PMID- 8444700 TI - Protection against platelet-activating factor-induced injury by interferon inducer in perfused rabbit lung. AB - Platelet-activating factor (PAF) and the interferons (IFN) are released during sepsis and the adult respiratory distress syndrome. The proinflammatory nature of PAF and anti-inflammatory property of IFN led us to investigate interactions between these two mediators in an isolated perfused lung (IPL) preparation. In the IPL, mean pulmonary arterial pressure (Ppa), lung weight gain, and peak airway pressure (Paw) were monitored continuously for 1 h in six groups of rabbits: 1) control, 2) the IFN-alpha/beta inducer polyinosinic:cytidylic acid (polyI:C) alone, 3) PAF alone, 4) polyI:C + PAF, 5) indomethacin + PAF, and 6) AA861 (a 5-lipoxygenase inhibitor) + PAF. At the end of 1 h, microvascular pressure was determined by double-occlusion technique and partition of total pulmonary vascular resistance (RT) was calculated. Serial eicosanoid concentrations in the perfusate also were measured. PAF increased Ppa, Paw, lung weight gain, and RT. These changes were associated with increased thromboxane B2 and decreased leukotriene production. PolyI:C, which induced high levels of serum IFN in rabbits, blocked the PAF-induced increase in Ppa, Paw, lung weight gain, and RT, similar to indomethacin and AA861. PolyI:C suppressed PAF-stimulated release of thromboxane B2 and increased leukotriene levels in the perfusate. The PAF-induced lung responses also were attenuated by pretreatment with human recombinant IFN. These data indicate that polyI:C protects against PAF-induced responses in the rabbit IPL, most likely via its induction of IFN. This effect is related in part to inhibition of thromboxane A2 production stimulated by PAF and leukotrienes. PMID- 8444701 TI - Capsaicin-induced bronchial vasodilation in dogs: central and peripheral neural mechanisms. AB - In 21 anesthetized dogs, we placed a flow probe around the right bronchial artery and examined changes in bronchial blood flow and bronchial vascular conductance when pulmonary C-fibers were stimulated by right atrial injection of capsaicin. When vagus nerves were intact, capsaicin evoked a pulmonary depressor chemoreflex and increased bronchial blood flow by 125% and bronchial vascular conductance by 175%; flow in an adjacent intercostal artery did not increase. Injection of color coded microspheres revealed that blood flow to mucosa of lower trachea and to a peripheral bronchus doubled, whereas flow to posterior tracheal wall increased little. Cooling (to -1 degree C) or cutting cervical vagi (in 17 dogs) abolished the pulmonary chemoreflex and abolished all bronchial vascular effects in nine dogs but 33% of the vasodilation persisted in eight. In five of six dogs, this persisting vasodilation was potentiated by phosphoramidon (a neutral endopeptidase inhibitor that retards breakdown of neuropeptides released by C fibers). Atropine reduced the capsaicin-induced bronchial vasodilation by approximately 30%. We conclude that the bronchial vasodilation was largely due to a centrally mediated vagal reflex and that a neuropeptide-dependent axon-reflex component was also present in about one-half the dogs. PMID- 8444702 TI - Diaphragmatic function after resistive breathing in vitamin E-deficient rats. AB - The effects of vitamin E deficiency on diaphragm function were studied at rest and after resistive breathing (RB) in Sprague-Dawley rats (wt 300-400 g). The animals were pair fed a vitamin E-deficient diet (E-def) or a matched vitamin E sufficient diet (E-suf). Each diet group was then further subdivided into a group that breathed unimpeded (control) and a second group that breathed through an inspiratory resistor until the animals were unable to sustain 70% of their maximum airway pressure. Diaphragm samples were obtained for analysis of thiobarbituric acid-reactive substances, glutathione (GSH) concentrations, and glutathione disulfide (GSSG) concentrations. In vitro isometric contractile studies were also performed and included twitch (Pt) and maximum tetanic (Po) tensions, force-frequency curves, fatigue index, and recovery index. Pt was significantly reduced in the E-suf RB group as well as both of the E-def groups. Po was also significantly reduced in both E-def groups. The E-def rats subjected to RB showed a significant decrease in tension at both high and low frequencies compared with the E-suf rats. Concentrations of diaphragm thiobarbituric acid reactive substances were significantly increased in both E-def groups. RB in both E-suf and E-def rats resulted in increases in diaphragm concentrations of GSSG and decreases in the GSH/GSSG ratios. We conclude that reduction of contractile function, lipid peroxidation, and activation of the GSH redox cycle occur with RB and that these effects are significantly increased in the presence of vitamin E deficiency. PMID- 8444703 TI - Identification of neutral endopeptidase mRNA in human nasal mucosa. AB - Neutral endopeptidase (NEP) may regulate peptide-induced inflammation in the upper respiratory tract. NEP mRNA was detected by Northern blotting in poly(A)+ mRNA prepared from human turbinates. NEP mRNA bands were detected at 3.9 and 1.8 kb. In situ hybridization identified NEP mRNA in epithelial cells, serous cells of submucosal glands, and vessel walls. The vacuoles of goblet and mucous cells were not stained, but it is likely that the cytoplasm of these cells contained some NEP mRNA. Radioactive in situ hybridization with 35S-UTP appeared to be more sensitive than nonradioactive in situ hybridization with biotin-UTP and immunogold detection. The NEP mRNA-containing cells identified by in situ hybridization were the same as those identified by immunohistochemistry to contain immunoreactive NEP. These NEP-containing cells have been previously shown to possess peptide receptors. This is consistent with the hypothesis that NEP on cells bearing peptide receptors may regulate neuropeptide-induced inflammation in human nasal mucosa. PMID- 8444704 TI - Cl- replacement alters the ventilatory response to central chemoreceptor stimulation. AB - To determine whether cerebrospinal fluid (CSF) Cl- has a role in determining the stimulus to the central respiratory chemoreceptors under conditions of constant CSF pH, CO2, and HCO3- concentrations, the ventral medullary surface of the anesthetized rat was perfused with mock CSF of various ion composition and pH. Four mock CSF perfusates were used: two normal pH control perfusions and two acidic solutions. One acidic perfusate was formulated in the traditional manner by substituting Cl- for HCO3-. The second acidic perfusate, and one of the normal pH control perfusates, had approximately 15% of the Cl- replaced with isethionate, an impermeant strong anion. When the two acidic solutions were perfused over the ventral medulla, consistently larger increases in both tidal volume and minute ventilation were observed with the isethionate-containing acidic solution, despite conditions of identical pH and PCO2. The unequal ventilatory effects of the two acidic perfusions suggest that Cl- transport may be a factor determining the stimulus to the central respiratory chemoreceptors. PMID- 8444705 TI - Orthostatic intolerance during a 13-day bed rest does not result from increased leg compliance. AB - Increased leg compliance (LC) has been proposed as a mechanism for orthostatic intolerance after spaceflight or bed rest. Using venous occlusion plethysmography with mercury-in-Silastic strain gauge, we evaluated LC before, during, and after a 13-day head-down (-6 degrees) bed rest in 10 men. LC was measured by the relationship between the increased calf areas (in cm2) at thigh cuff occlusions of 20, 30, 50, 70, and 80 mmHg. Orthostatic tolerance was evaluated by a presyncopal-limited lower body negative pressure test (PSL-LBNP) before and after bed rest. The 10 subjects were divided into TOL (n = 5) and INT (n = 5) groups for which the orthostatic tolerance was similar and lower after bed rest, respectively. For TOL (INT) before bed rest, calf area increases were 2.2 +/- 0.5 (SE) (1.3 +/- 0.4), 3.5 +/- 0.7 (2.3 +/- 0.5), 5.0 +/- 0.9 (3.5 +/- 0.6), 5.6 +/- 0.9 (4.4 +/- 0.6), and 6.4 +/- 1.1 (4.7 +/- 0.6) cm2 for thigh occlusion pressures of 20, 30, 50, 70, and 80 mmHg, respectively. Neither for INT nor for TOL were these results significantly changed by bed rest. These results suggest that other mechanisms than increased LC have to be taken into account to explain the decreased orthostatic tolerance induced by this 13-day bed rest. PMID- 8444706 TI - Increased insulin suppression of plasma free fatty acid concentration in exercise trained rats. AB - The effect of exercise training on the insulin suppression of plasma free fatty acid (FFA) concentrations was studied in unanesthetized rats with the hyperinsulinemic-euglycemic clamp technique. Seven rats trained (TR) for 3 h/day by continuous swimming during 8 wk were compared with 6 untrained (UT) body weight-matched rats. Both TR and UT rats were submitted to an exercise swimming session 18 h before the clamp. A smaller mean diameter of adipocytes sampled from the epididymal fat depot was measured in TR animals. The total quantity of glucose infused to maintain euglycemia was 2.2 times higher in TR than in UT animals. No significant differences in plasma insulin concentrations were found between the two groups throughout the experiment. Insulin infusions resulted in a 60% decrease of plasma FFA in TR rats (mean value: from 0.46 to 0.18 mM) compared with 27% in UT animals (mean value: from 0.45 to 0.33 mM). The data indicate a greater ability of insulin to suppress plasma FFA levels with exercise training, which suggests an increased antilipolytic action of insulin in adipocytes under this condition. PMID- 8444707 TI - Hypoxic ventilatory responsiveness in Tibetan compared with Han residents of 3,658 m. AB - Lifelong high-altitude residents of North and South America acquire blunted hypoxic ventilatory responses and exhibit decreased ventilation compared with acclimatized newcomers. The ventilatory characteristics of Himalayan high altitude residents are of interest in the light of their reportedly lower hemoglobin levels and legendary exercise performance. Until recently, Sherpas have been the only Himalayan population available for study. To determine whether Tibetans exhibited levels of ventilation and hypoxic ventilatory drives that were as great as acclimatized newcomers, we compared 27 lifelong Tibetan residents of Lhasa, Tibet, China (3,658 m) with 30 acclimatized Han ("Chinese") newcomers matched for age, body size, and extent of exercise training. During room air breathing, minute ventilation was greater in the Tibetan than in the Han young men because of an increased respiratory frequency, but arterial O2 saturation and end-tidal PCO2 did not differ, indicating similar levels of effective alveolar ventilation. The Tibetan subjects had higher hypoxic ventilatory response shape parameter A values and hypercapnic ventilatory responsiveness than the Han subjects. Among the Han subjects, duration of high-altitude residence correlated with the degree of blunting of the hypoxic ventilatory drive. Paradoxically, hyperoxia (inspired O2 fraction 0.70) increased minute ventilation and decreased end-tidal PCO2 in the Tibetan but not in the Han men. We concluded that lifelong Tibetan residents of high altitude neither hypoventilated nor exhibited blunted hypoxic ventilatory responses compared with acclimatized Han newcomers, suggesting that the effects of lifelong high-altitude residence on ventilation and ventilatory response to hypoxia differ in Tibetan compared with other high altitude populations. PMID- 8444708 TI - Minimal hypoxic pulmonary hypertension in normal Tibetans at 3,658 m. AB - Elevated pulmonary arterial pressure in high-altitude residents may be a maladaptive response to chronic hypoxia. If so, well-adapted populations would be expected to have pulmonary arterial pressures that are similar to sea-level values. Five normal male 22-yr-old lifelong residents of > or = 3,600 m who were of Tibetan descent were studied in Lhasa (3,658 m) at rest and during near maximal upright ergometer exercise. We found that resting mean pulmonary arterial pressure [15 +/- 1 (SE) mmHg] and pulmonary vascular resistance (1.8 +/- 0.2 Wood units) were within sea-level norms and were little changed while subjects breathed a hypoxic gas mixture [arterial O2 pressure (PaO2) = 36 +/- 2 Torr]. Near-maximal exercise [87 +/- 13% maximal O2 uptake (VO2max)] increased cardiac output more than threefold to values of 18.3 +/- 1.2 l/min but did not elevate pulmonary vascular resistance. Breathing 100% O2 during near-maximal exercise did not reduce pulmonary arterial pressure or vascular resistance. We concluded that this small sample of healthy Tibetans with lifelong residence > or = 3,658 m had resting pulmonary arterial pressures that were normal by sea-level standards and exhibited minimal hypoxic pulmonary vasoconstriction, both at rest and during exercise. These findings are consistent with remarkable cardiac performance and high-altitude adaptation. PMID- 8444709 TI - Cerebral blood velocity and other cardiovascular responses to 2 days of head-down tilt. AB - Spaceflight induces a cephalad redistribution of fluid volume and blood flow within the human body, and space motion sickness, which is a problem during the first few days of spaceflight, could be related to these changes in fluid status and in blood flow of the cerebrum and vestibular system. To evaluate possible changes in cerebral blood flow during simulated weightlessness, we measured blood velocity in the middle cerebral artery (MCA) along with retinal vascular diameters, intraocular pressure, impedance cardiography, and sphygmomanometry on nine men (26.2 +/- 6.6 yr) morning and evening for 2 days during continuous 10 degrees head-down tilt (HDT). When subjects went from seated to head-down bed rest, their heart rate and retinal diameters decreased, and intraocular pressures increased. After 48 h of HDT, blood flow velocity in the MCA was decreased and thoracic impedance was increased, indicating less fluid in the thorax. Percent changes in blood flow velocities in the MCA after 48 h of HDT were inversely correlated with percent changes in retinal vascular diameters. Blood flow velocities in the MCA were inversely correlated (intersubject) with arterial pressures and retinal vascular diameters. Heart rate, stroke volume, cardiac output, systolic arterial pressure, and at times pulse pressure and blood flow velocities in the MCA were greater in the evening. Total peripheral resistance was higher in the morning. Although cerebral blood velocity is reduced after subjects are head down for 2 days, the inverse relationship with retinal vessel diameters, which have control analogous to that of cerebral vessels, indicates cerebral blood flow is not reduced. PMID- 8444710 TI - Effects of fatigue on the length-tetanic force relationship of the rat diaphragm. AB - It has been established that the in vivo operating length of the diaphragm corresponds to a wide range of the ascending limb of its length-tetanic force relationship. To investigate the length-dependent effects of fatigue on maximum force production, we constructed length-tetanic force relationships of rat costal diaphragm strips in vitro before and after fatigue induced by repetitive supramaximal electrical field stimulations at optimal length. Two levels of fatigue were studied (i.e., force reductions of 40 and 65% at optimal length). Results indicate that fatigue, when evaluated with high-frequency stimulations, causes a proportionately larger decrease in tetanic force at short muscle lengths as seen by a smaller control force-to-fatigue force ratio and an apparent shift in the length at which active force is zero. A possible explanation for the results obtained is failure of propagation of membrane depolarization into the t tubule system at short muscle lengths, which is aggravated by fatigue evaluated by high-frequency stimulation. PMID- 8444711 TI - Acute effect of cigarette smoke on breathing is attenuated by chronic smoking in rats. AB - To determine whether the irritant effect of cigarette smoke on breathing was affected by chronic exposure to smoke, two groups of sixteen young male Sprague Dawley rats were exposed daily to fresh cigarette smoke (treated group) or air (control group) for 4-8 wk. Acute ventilatory response to cigarette smoke (50% concn, 6 ml volume) inhaled via a tracheal cannula was then studied under anesthesia and compared between the two groups. Inhalation of either cigarette smoke or gas phase smoke induced an immediate and transient apnea or bradypnea that was completely abolished by bilateral vagotomy in both groups, suggesting the involvement of vagal bronchopulmonary afferents. However, the apneic response was markedly attenuated in the treated group. Inhalation of cigarette smoke, but not the gas phase smoke, also induced a delayed tachypneic response after the initial apnea. The tachypneic response was again significantly smaller in treated rats, and this difference between the two groups was eliminated after vagotomy. On the basis of these results, we suggest that a reduced stimulatory effect on vagal bronchopulmonary sensory receptors was responsible for the attenuated ventilatory responses to smoke observed in treated rats. PMID- 8444713 TI - Respiratory response to pulmonary vascular congestion in intact conscious dogs. AB - Clinical disorders associated with pulmonary venous hypertension frequently result in tachypnea and hyperpnea. The response to pulmonary vascular congestion (PVC) in anesthetized or decerebrate animals has consisted of modest and bidirectional changes in respiratory rate with no hyperpnea. We hypothesized that anesthesia or decerebration in previous animal experiments may have attenuated the hyperpneic response that would otherwise have been evident. A conscious dog model was developed in which the left lower lobe (LLL) pulmonary circulation could be reversibly isolated and pressurized. Occluders were placed outside the LLL pulmonary artery (PA) and vein. Two fine catheters were introduced through the wall of the LLLPA distal to the arterial occluder. A pleural catheter was used to monitor pleural pressure swings. After recovery from surgery PVC was initiated by inflation of the occluders and injection of warm saline or fresh warm blood through one of the catheters. PVC resulted in decreased breathing frequency and hypopnea in six of seven intact unanesthetized dogs. The remaining dog exhibited a transient rapid shallow breathing pattern. In four dogs tested using the same preparation under anesthesia, the response to PVC was an increase instead of a decrease in breathing frequency. We conclude that the presence of higher brain function does not promote tachypnea or hyperpnea in response to PVC. Mechanisms other than PVC, per se, likely account for the tachypnea and hyperpnea observed in clinical disorders associated with pulmonary venous hypertension. PMID- 8444712 TI - Maintained endothelium-dependent pulmonary vasodilation following chronic hypoxia in the rat. AB - We have previously demonstrated that arginine vasopressin (AVP) dilates the preconstricted pulmonary vasculature via the release of nitric oxide (NO). However, recent evidence suggests that NO release in response to other agents may be suppressed in lungs from animals that have been chronically exposed to hypoxia. The purpose of the present experiment was to determine whether vasopressinergic pulmonary vasodilation is similarly affected by chronic exposure to hypoxia (barometric pressure = 380 Torr for 4 wk). Inhibition of NO synthesis with N omega-nitro-L-arginine (L-NNA) had no effect on baseline perfusion pressure in isolated salt-perfused lungs from either control or chronically hypoxic rats. Similarly, pulmonary vasodilatory responses to AVP and the calcium ionophore A23187 were unaffected by chronic hypoxic exposure. Pretreatment with the cyclooxygenase inhibitor meclofenamate did not alter vasopressinergic pulmonary vasodilation in lungs from either control or chronically hypoxic animals, ruling out involvement of vasodilator prostaglandins in the response to AVP. In contrast, vasodilatory responses to both AVP and A23187 were inhibited by L-NNA pretreatment not only in lungs from control animals but also in lungs from chronically hypoxic rats, suggesting the involvement of NO in the vasodilatory response. The inhibition by L-NNA was reversible by prior addition of excess L arginine but not by D-arginine. In addition, vasodilatory responses to the endothelium-independent vasodilators sodium nitroprusside and isoproterenol were unaffected by chronic hypoxic exposure. We conclude that endothelium-dependent vasodilation remains intact in male Sprague-Dawley rats after chronic hypoxic exposure. PMID- 8444714 TI - Higher levels of erythrocyte membrane fluidity in sprinters and long-distance runners. AB - Erythrocyte membrane fluidity was measured in male sprinters and long-distance runners by a spin-label method. The membrane fluidity was higher in long-distance runners than in sedentary subjects for both measurements by use of two stearic acid spin labels (SAL), 12- and 16-SAL, which represent the fluidity at two different depths of lipid bilayer. In the 12-SAL measurement, higher levels were also evident in sprinters than in sedentary subjects. Increases in the C20:5, C22:5, and total polyunsaturated acyl chains were evident in membrane phospholipids, whereas the C18 and total saturated acyl chains were decreased in long-distance runners compared with sedentary subjects. Only levels of C22:5 were higher in the sprinters than the sedentary subjects. Membrane cholesterol and phospholipid classes did not differ among the three groups. A higher level of erythrocyte membrane fluidity was observed in the athletes, more obviously in the long-distance runners, which was related to the altered phospholipid acyl chain composition. The change may contribute to the beneficial effects on erythrocyte functions related to microcirculation in athletes. PMID- 8444715 TI - Intended rather than actual movement velocity determines velocity-specific training response. AB - Eight men and eight women trained 3 days/wk for 16 wk by doing attempted ballistic unilateral ankle dorsiflexions against resistance that either rendered the resultant contractions isometric (one limb) or allowed a relatively high velocity (5.23 rad/s on an isokinetic dynamometer) movement (other limb). Training sessions consisted of five sets of 10 contractions of each type. Training produced the same high-velocity-specific training response in both limbs (P < 0.001). Peak torque increased most at 5.23 rad/s (38%) in comparison to lower velocities (0, 0.26, 0.52, 1.04, 1.55, 3.02, and 4.19 rad/s). Both limbs also showed similar increases in voluntary isometric rate of torque development (26%) and relaxation (47%) and in evoked tetanus rate of torque development (14%). A similar decrease in evoked twitch time to peak torque (6%) and half relaxation time (11%) was also observed. Thus, all of these training responses, previously associated specifically with high-velocity resistance training, were produced by a training regimen that prevented an actual rapid movement through a range of movement. The results suggest that the principal stimuli for the high velocity training response are the repeated attempts to perform ballistic contractions and the high rate of force development of the ensuing contraction. The type of muscle action (isometric or concentric) appears to be of lesser importance. PMID- 8444716 TI - Changes in respiratory mechanics with age. AB - A cross-sectional survey involving 51 children, ranging in age from 3 wk to 15 yr, was performed to examine the changes in respiratory mechanics with age in mechanically ventilated children, using both a single-compartment model of the respiratory system and a more sophisticated two-compartment model. Children were studied while under anesthesia for urological surgery and were considered to have normal lungs. They were paralyzed and mechanically ventilated throughout measurements. Respiratory mechanics were measured during ventilation by applying a single-compartment model and by using multilinear regression to calculate dynamic compliance and respiratory system resistance (Rrs). We then used the interrupter technique, which allowed us to partition Rrs into airway resistance and a tissue viscoelastic component known as Pdif. A static volume-pressure curve was constructed from multiple occlusions made at different lung volumes throughout expiration, and static compliance was determined. Rrs and airway resistance decreased as height increased. There was a progressive increase in respiratory system compliance with height. Pdif fell in the first 2 yr of life and then subsequently increased after the age of approximately 5 yr. PMID- 8444717 TI - Peripheral chemoreceptor function in children with the congenital central hypoventilation syndrome. AB - In children with the congenital central hypoventilation syndrome (CCHS), some patients require mechanical ventilation during sleep, whereas others need respiratory assistance even when awake. The cause of this disparity is unclear. We hypothesized that differences in peripheral chemoreceptor response (PCR) could provide an explanatory mechanism for this disparity in clinical manifestations. PCR was measured in five children with CCHS and five sex- and age-matched controls by measuring the ventilatory responses induced by 100% O2 breathing, five tidal breaths of 100% N2, and vital capacity breaths of 5% and 15% CO2 in O2 and 5% CO2-95% N2. Tidal breathing of 100% O2 resulted in similar ventilatory responses in CCHS patients and controls with various changes dependent on the method of analysis of response used. Acute hypoxia by N2 tidal breathing resulted in a 39.2 +/- 22% increase in respiratory rate in CCHS patients and a 15.1 +/- 11.1% increase in controls (P < 0.05), with similar increases in minute ventilation (VE) of 124 +/- 69% and 85 +/- 11%, respectively. Vital capacity breaths of each of the CO2-containing gas mixtures induced similar increases in VE in CCHS patients and controls. The changes in VE obtained with 15% CO2-85% O2 and with 5% CO2-95% N2 were significantly greater than those with 5% CO2-95% O2, suggesting a dose-dependent response as well as additive effects of hypercapnic and hypoxic stimuli. We conclude that the PCR, when assessed by acute hypoxia, hyperoxia, or hypercapnia, is present and intact in CCHS children who are able to sustain adequate ventilation during wakefulness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444718 TI - Chronic exercise enhances in vivo and in vitro cytotoxic mechanisms of natural immunity in mice. AB - This study investigated the influence of 9 wk of chronic exercise on natural cytotoxicity in male C3H mice. Both in vivo cytotoxicity (pulmonary vasculature) and in vitro cytotoxicity (spleen) were determined for voluntary (wheel running; n = 30) and forced (treadmill running, 15 m/min, 30 min/day; n = 30) exercise protocols. A sedentary control group (n = 30) and a treadmill control group (5 m/min, 5 min/day; n = 30) were also included. After 9 wk of chronic exercise, submaximal exercise O2 uptake was reduced in the wheel-running group relative to that in sedentary or treadmill-trained mice. Maximal citrate synthase activity of soleus muscle was higher in treadmill-trained group compared with that in sedentary or wheel-running mice. Chronic exercise consistently reduced percent retention of CIRAS 3 tumor cells in the lungs of treadmill- (15.3 +/- 1.4) and wheel- (17.9 +/- 1.4) trained mice below that of sedentary (29.5 +/- 2.7) and treadmill control (25.8 +/- 1.8) groups (P < 0.001). Injection of anti-asialo GM1 (ASGM1) antibody increased tumor cell retention in the lungs for all groups but did not alter the differences between activity conditions. In vitro cytotoxicity was enhanced in treadmill- and wheel-trained mice relative to that in sedentary controls but was not elevated in the treadmill control group. Anti-ASGM1 injection eliminated in vitro cytotoxicity for all groups. Chronic exercise slightly increased the frequency of ASGM1-positive splenocytes in treadmill trained mice only. These results indicate that chronic exercise enhances natural cytotoxic mechanisms in vivo and in vitro and that this enhancement is present for both forced and voluntary exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444719 TI - Effects of 5-hydroxytryptamine and 5-hydroxytryptophan infusion on the human cough reflex. AB - In some species serotonin (5-HT) has been shown to act as a central modulator of the cough reflex. To investigate whether serotonergic mechanisms influence the control of the human cough reflex, we have induced cough responses before and during infusions of 5-HT; its precursor 5-hydroxytryptophan (5-HTP), which, in contrast to 5-HT, crosses the blood-brain barrier; and saline control. At the start of each study day, eight normal male volunteers were challenged with a single inhalation of a solution lacking chloride ions (0.15 M sodium bicarbonate) and a single breath of capsaicin during a sham infusion. After 3 h they received repeat cough challenges during experimental infusions of 5-HT, 5-HTP, or saline control, which were given randomly and single blind. Heart rate, respiratory rate, and blood pressure were measured before, during, and after each infusion. Both 5-HT and 5-HTP reduced cough responses to the chloride-deficient solution (P = 0.035 and P = 0.017, respectively) with respect to saline control, whereas neither infusion reduced responses to capsaicin. 5-HT caused a transient increase in heart rate that was not observed with a similar dose of 5-HTP or saline (P < 0.01). Respiratory rate and blood pressure were not affected by experimental infusions but rose during cough challenge. We conclude that 5-HT exerts an inhibitory influence over the human cough reflex at peripheral and possibly central sites. PMID- 8444720 TI - Interactions between Hb, Mg, DPG, ATP, and Cl determine the change in Hb-O2 affinity at high altitude. AB - Ascent to high altitude (HA) causes an increase in erythrocyte 2,3 diphsophoglycerate (DPG) and standard PO2 at 50% O2 saturation, PCO2 40 Torr, and blood pH 7.4 (P50,st). We studied the early phase of acclimatization to HA of mountaineers without and with a history of HA pulmonary edema. Tests were performed before ascent and after arrival at HA (4,559 m), approximately 22 h after the departure from low altitude (HA1) and on the following 3 days at HA (HA2-HA4). We investigated the relation between changes in DPG and P50,st, since at moderate altitude P50,st increases more rapidly than DPG, indicating that other factors may contribute to the change in P50,st. Combined effects of interaction between allosteric effectors of hemoglobin (Hb) (DPG, ATP, Cl) and Mg, which competes with Hb for DPG and ATP binding, might explain that phenomenon. Therefore concentrations of liganded Hb species were calculated from the total erythrocyte concentrations of the ligands by use of published binding constants and were related to changes in Hb-O2 affinity. P50,st increased at HA by approximately 4.5 Torr; the concentration of total DPG and ATP increased by 28 and 19%, respectively. Whereas P50,st reached a plateau already at HA1, the concentration of DPG reached its highest value at HA4. The erythrocyte Cl concentration decreased, whereas cellular Hb and Mg concentrations increased slightly. The sum of concentrations of all liganded Hb species increased, reaching 79% of its total change within 22 h after ascent; this can mainly be attributed to the change in the concentration of Hb[DPG] (+77% of total increase).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444721 TI - Insulin-like growth factor immunoreactivity increases in muscle after acute eccentric contractions. AB - The purpose of the study was to note whether insulin-like growth factor (IGF) immunoreactivity increased after eccentric contractions. IGF immunoreactivity in the rat tibialis anterior muscle was measured on 5 successive days (4-5 rats/group, n = 28) after an acute bout of 192 eccentric contractions elicited by electrical stimulation. The muscle tissue sections were immunocytochemically processed with rabbit anti-human IGF-I serum. Immunoreactivity was analyzed with videomicroscopy and computer-aided image processing. Four days after eccentric contractions, IGF immunoreactivity was significantly higher than control [0.081 +/- 0.073 (SD) absorbance at 480 nm vs. 0.026 +/- 0.018; P < 0.05]. The increases in IGF-I immunoreactivity were mostly within the muscle fibers. These results suggest that an acute bout of eccentric exercise increases IGF-I immunoreactivity in rat type II muscle 4 days postexercise. PMID- 8444722 TI - Effect of posture on static lung volumes and pulmonary mechanics in pneumonectomized rabbits. AB - Static lung volumes, lung (CL) and respiratory system compliance (Crs), and the slope of phase III of the single-breath O2 test (slope III) were measured in rabbits in the prone, supine, and right and left lateral positions. Control rabbits, rabbits that had the left lung removed (Px), and rabbits that had the left lung removed and replaced with wax (Px + W) were studied. Surgeries were performed > or = 7 wk before study. Lung volumes, Crs, and slope III were not different among groups. Total lung capacity, vital capacity, residual volume, Crs, and slope III were smallest in all rabbits in the prone position. Functional residual capacity and expiratory reserve volume were unaffected by posture in control rabbits but were larger in Px and Px + W rabbits in the left lateral position. CL was unaffected by posture but was smaller in Px and Px + W rabbits than in control rabbits. Pneumonectomy-induced changes in lung shape altered the effect of posture on functional residual capacity but not on regional lung function, as assessed by the single-breath O2 test. PMID- 8444723 TI - Protective effects of anti-O polysaccharide and anti-lipid A monoclonal antibodies on pulmonary hemodynamics. AB - Monoclonal antibodies (MAbs) directed to endotoxin can protect in some animal models against the pathophysiological effects of endotoxin infusion. When 0.02 microgram/kg of lipopolysaccharide (LPS) derived from Escherichia coli O111:B4 was incubated in vitro for 2 h with the murine immunoglobulin G MAb, 5B10, directed against the O-polysaccharide antigenic domain of E. coli O111:B4 and then the mixture was infused into sheep, we noted significant protection. The second temperature peak was decreased (P < 0.05 vs. LPS control). The acute pulmonary arterial pressure elevation was diminished (mean peak pulmonary arterial pressure 23.2 +/- 2.5 mmHg, P < 0.05 vs. LPS control), and the peak plasma thromboxane B2 level was reduced (mean peak thromboxane B2 level 0.50 +/- 0.15 ng/ml, P < 0.05 vs. LPS control). In contrast, preincubation of the LPS with a human immunoglobulin M MAb, HA-1A, directed against the core glycolipid of the LPS molecule provided no protective effects in this sheep model. This finding is in agreement with recent studies reporting HA-1A may bind to antibiotic-treated bacteria but not to purified smooth LPS. PMID- 8444724 TI - Blood flow to respiratory muscles and major organs during inspiratory flow resistive loads. AB - To determine whether diaphragmatic fatigue in the intact animal subjected to loaded breathing is associated with a decrease in diaphragmatic blood flow, seven unanesthetized sheep were subjected to severe inspiratory flow resistive (IFR) loads that led to a decrease in transdiaphragmatic pressure (Pdi) and a rise in arterial PCO2 (PaCO2). Blood flow to the diaphragm, other respiratory muscles, limb muscles, and major organs was measured using the radionuclide-labeled microsphere method. With these loads blood flow increased to the diaphragm (621 +/- 242%) and all the other inspiratory and expiratory diaphragm (621 +/- 242%) and all the other inspiratory and expiratory muscles; there was no statistically significant change in blood flow to these muscles at the time when Pdi decreased and PaCO2 rose. Blood flow also increased to the heart (103 +/- 34%), brain (212 +/- 39%), and adrenals (76 +/- 9%), whereas pancreatic flow decreased (-66 +/- 14%). Limb muscle blood flow remained unchanged. We conclude that in unanesthetized sheep subjected to IFR loads 1) we did not demonstrate a decrease in respiratory muscle blood flow associated with diaphragmatic fatigue and ventilatory failure, and 2) there is a redistribution of blood flow among major organs. PMID- 8444725 TI - Lactate kinetics in resting and exercising forearms during moderate-intensity supine leg exercise. AB - Arterial blood lactate was elevated by supine leg exercise (20 min at approximately 65% maximal oxygen uptake) in five untrained male subjects, and the contribution to blood lactate removal from passive uptake vs. metabolic disposal was compared in resting and lightly exercising (15% maximal voluntary contraction static handgrip) forearm skeletal muscle. An integrated form of the Fick equation was used to predict venous lactate levels resulting solely from passive equilibration of lactate between incoming arterial blood and the forearm muscles. In the resting forearm, predicted and measured venous lactate levels were closely correlated during the exercise period (r = 0.995, P < 0.001), indicating that lactate removal could be accounted for in terms of passive uptake alone. In the lightly exercising forearm, measured venous lactate levels were higher than both the arterial and predicted venous levels, indicating net lactate production. It was concluded that most of the blood lactate generated by moderate-intensity supine leg exercise is taken up passively and not metabolized by resting skeletal muscle and that the rate of lactate disposal is unlikely to be enhanced in lightly exercising muscle. PMID- 8444726 TI - Chronic catheterization of external iliac vessels in growing cattle. AB - Bovine preparations that allow for in vivo measurement of metabolic fluxes across the hindlimb often suffer from limited durability, usually because of failure of the venous catheter. A catheterization procedure that virtually eliminates this occurrence is presented. A silicone rubber catheter is implanted permanently in the femoral vein. It accommodates the repeated insertion and removal at each sampling session of a temporary sampling catheter. A simple and reliable method ensures the positioning of this catheter in the external iliac vein of a conscious, normally standing animal. The application of this approach allowed the study of hindlimb metabolism of cattle for up to 4 mo without a single planned sampling session postponed or missed. This preparation is particularly well suited for studies that require repeated measurements of hindlimb metabolism on the same animals over a period of many months. PMID- 8444727 TI - Effects of different heavy-resistance exercise protocols on plasma beta-endorphin concentrations. AB - To examine the changes of plasma beta-endorphin (beta-EP) concentrations in response to various heavy-resistance exercise protocols, eight healthy male subjects randomly performed each of six heavy-resistance exercise protocols, which consisted of identically ordered exercises carefully designed to control for the repetition maximum (RM) resistance (5 vs. 10 RM), rest period length (1 vs. 3 min), and total work (joules). Plasma beta-EP, ammonia, whole blood lactate and serum cortisol, creatine kinase, urea, and creatinine were determined preexercise, midexercise, immediately postexercise, and at various time points after the exercise session (5 min-48 h), depending on the specific blood variable examined. Only the high total work-exercise protocol [1 min rest, 10 RM load (H10/1)] demonstrated significant increases in plasma beta-EP and serum cortisol at midexercise and 0, 5, and 15 min postexercise. Increases in lactate were observed after all protocols, but the largest increases were observed after the H10/1 protocol. Within the H10/1 protocol, lactate concentrations were correlated (r = 0.82, P < 0.05) with plasma beta-EP concentrations. Cortisol increases were significantly correlated (r = 0.84) with 24-h peak creatine kinase values. The primary finding of this investigation was that beta-EP responds differently to various heavy-resistance exercise protocols. In heavy-resistance exercise, it appears that the duration of the force production and the length of the rest periods between sets are key exercise variables that influence increases in plasma beta-EP and serum cortisol concentrations. Furthermore the H10/1 protocol's significant challenge to the acid-base status of the blood, due to marked increases in whole blood lactate, may be associated with mechanisms modulating peripheral blood concentrations of beta-EP and cortisol. PMID- 8444728 TI - Airway and vascular effects of 8-epi-prostaglandin F2 alpha in isolated perfused rat lung. AB - The effects of 8-epi-prostaglandin (PG) F2 alpha, a recently discovered noncyclooxygenase free radical-catalyzed product of arachidonic acid, on pulmonary vascular and airway tone, its potency, and its mechanism of action were studied. Progressively increasing bolus doses (1.0, 5.0, 10.0, and 20.0 micrograms) of 8-epi-PGF2 alpha were injected into the pulmonary artery catheter of 18 isolated rat lungs, and a single dose (40.0 micrograms) was injected into 7 additional rat lungs. The lungs were perfused with Krebs-Henseleit buffer solution containing 3% bovine serum albumin at 50 ml.kg-1.min-1 during ventilation with 21% O2-5% CO2-74% N2. 8-Epi-PGF2 alpha caused rapid pulmonary vascular and airway constrictor responses, which were followed by a gradual return over 10 min to baseline levels. Double vascular occlusion at peak rise in pulmonary arterial pressure (Ppa) revealed a 28% increase in arterial resistance. The rise in Ppa with 20 micrograms of 8-epi-PGF2 alpha was approximately twofold greater than with 20 micrograms of the cyclooxygenase-derived prostaglandin PGF2 alpha. The addition of 100 microM N-nitro-L-arginine, a blocker of endothelium derived relaxing factor, in the perfusate potentiated the rise in Ppa by 244%. Injection of 40 micrograms of rat atrial natriuretic factor at peak response to 20 micrograms of 8-epi-PGF2 alpha accelerated the return to baseline Ppa, resistance to airflow across the lung, and dynamic lung compliance values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444729 TI - Flexible intravenous microdialysis probe for blood sampling in freely moving rats. AB - A flexible intravenous microdialysis probe was constructed from Silastic tubing (0.5 mm ID and 1.0 mm OD), with a cellulose hollow fiber tip 0.2 mm in diameter and 25 mm long with a 6,000 mol wt cut off. In vitro tests showed relative recovery rates of 39.1 +/- 1.9% for epinephrine. In vivo tests in freely moving rats, 36 h and 7 days after surgery, showed stable amounts of epinephrine and glucose. After intraperitoneal injections of 2-deoxy-D-glucose, circulating levels of epinephrine and glucose increased significantly. Similar results were obtained several days after implantation of the probe. We conclude that in situations where prolonged blood sampling is necessary, the flexible microdialysis probe provides a reliable means of accessing circulating levels of neuroactive compounds, nutrients, metabolites, and drugs. PMID- 8444730 TI - Water-sealed spirometer for measurements in newborns and infants. AB - Details are given of two spirometers for use in neonates and infants < 12 mo old. The minimum volumes are 520 and 670 ml, respectively. The maximum volume changes that can be recorded are 250 and 450 ml, respectively. The minimal detectable volume changes are 0.4 and 0.6 ml, respectively. Rebreathing of dead space gas is prevented by a fan producing a flow of 6.2 and 10.2 l/min, respectively; 100% gas mixing after injecting a gas bolus in the two spirometers is achieved in 5.7 and 6.6 s, respectively. Resistance to airflow is 0.2 kPa.l-1.s (2 cmH2O.l-1.s) at 150 ml/s in both spirometers. The frequency response of both instruments is flat to 6 cycles/s. The instruments can be easily cleaned and are suitable for bedside measurements. PMID- 8444731 TI - Fast-response whole body indirect calorimeters for infants. AB - Portable whole body indirect calorimeters were constructed for full-term (2.5- to 8-kg) and preterm (1- to 2.5-kg) infants. A new calibration system significantly increased the accuracy of flowmeters and gas analyzers. Performance tests with N2 and CO2 infusions and butane combustion demonstrated that the error of individual measurements of O2 consumption and CO2 production were within +/- 2%. The measured error was close to the theoretical uncertainty of approximately +/- 1% calculated from test results of the flowmeters and gas analyzers. System response to a step change in butane combustion rate exceeded 90% within 2 min. Error of +/ 2% and response of 2 min are likely to be the practical lower limits for whole body infant indirect calorimeters with current technology. The calorimeters demonstrated a rapid increase in O2 consumption after feeding (preterm infants) and in the transition from non-rapid-eye-movement to rapid-eye-movement sleep stages (full-term infants). PMID- 8444732 TI - Indirect calorimetry with a hood: flow requirements, accuracy, and minute ventilation measurement. AB - Flow-dilution-based hood systems for indirect calorimetry eliminate the conventional mouthpiece or mask of sealed-circuit systems allow measurements with improved patient comfort. This feature is particularly relevant when measurements are made over long periods of time or are repeated often. The flow of air pulled through the hood into the calorimeter in these systems is necessary to clear CO2 from inside the hood. The errors in these systems are greater than those in the sealed-circuit systems and are proportional to the flow. We show that the CO2 concentration within the hood at steady state does not depend on hood size. We describe the accuracy in determination of O2 consumption (VO2), CO2 production, and respiratory exchange ratio with a hood system as a function of the accuracy of the O2 and CO2 analyzers and the water vapor in collected gas. For example, we show that if there is a 1% error in O2 concentration, the percent error in VO2 changes from 5% in a sealed circuit to 51% when a cleansing flow of 50 l/min is introduced. The error in VO2 caused by a 5% error in CO2 determination is 10.6% at this cleansing flow. Removal of 90% of the water vapor (instead of 100%) before analysis of the expired gas introduces a 15.8% error in VO2. By use of the equations described, the accuracy of any measurement system can be determined. In addition, we demonstrate that the measurement of ventilation, usually lost in a hood system, can be preserved using dual pneumotachographs and a sealed hood. PMID- 8444733 TI - Young and old subjects matched for aerobic capacity have similar noradrenergic responses to exercise. AB - Sympathetic nervous system activity as indicated by circulating norepinephrine has been demonstrated to increase with advancing chronological age both at rest and during submaximal exercise. Much of the earlier work investigating this aging phenomenon used a younger group that had a higher peak oxygen consumption (VO2) than did the older group, which made comparisons difficult. In the present study, young [n = 7, 36 +/- 1.0 (SE) yr] and old subjects (n = 8, 61 +/- 1.2 yr) were matched on peak VO2 and then exercised at approximately the same relative submaximal VO2 (75%) and power output on a cycle ergometer for 21 min. Blood samples were collected at rest and in the 7th, 14th, and last minute of a 21-min exercise bout via an indwelling catheter in an antecubital vein. The norepinephrine responses for the young and old groups, respectively, were as follows: rest, 486 +/- 111 vs. 673 +/- 108; 7 min, 1,258 +/- 255 vs. 1,185 +/- 172; 14 min, 1,639 +/- 316 vs. 1,528 +/- 288; and 21 min, 2,038 +/- 488 vs. 1,936 +/- 453 pg/ml. These responses were not significantly different between the groups at any time period. The epinephrine values for the age groups were not statistically different: rest, 115 +/- 60 vs 88 +/- 51; 7 min, 140 +/- 18 vs. 326 +/- 88; 14 min, 216 +/- 33 vs. 366 +/- 104; and 21 min, 324 +/- 100 vs. 447 +/- 113 pg/ml.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444734 TI - Age-related changes of human aortic flow wave velocity measured noninvasively by magnetic resonance imaging. AB - We have used magnetic resonance imaging with cine velocity mapping to measure flow wave velocity in the thoracic aorta of 20 healthy volunteers of different ages. We have also studied the relationship between propagation of flow wave velocity and regional aortic compliance. Aortic flow velocity increased linearly with age (r = 0.87), and there was a significant difference between the youngest decade [age 10-19, mean velocity 4.3 +/- 0.7 (SD) m/s] and the oldest decade studied (age 50-59, mean velocity 7.2 +/- 0.2 m/s). Flow wave velocity (m/s) was negatively correlated with ascending aortic compliance (microliter/mmHg) (r = 0.75). Magnetic resonance imaging is a noninvasive method for measurement of aortic flow wave velocity that is an important parameter in assessing arterial wall mechanics and blood flow dynamic. PMID- 8444735 TI - Effect of a single air dive on pulmonary diffusing capacity in professional divers. AB - The aim of this study was to determine whether venous gas embolism after a single air dive, evaluated using precordial Doppler monitoring, was associated with alterations in spirometry, lung volumes, arterial blood gases, or pulmonary diffusing capacity for carbon monoxide (DLCO). Postdive time course monitoring of pulmonary function was undertaken in 10 professional divers exposed to absolute air pressure of 5.5 bar for 25 min in a dry walk-in chamber. The US Navy decompression table was followed. Venous bubbles were detected by precordial Doppler monitoring. Two types of decompression were used: air and 100% O2 applied for 21 min during decompression stops. Spirometry, flow-volume, and body plethysmography parameters were unchanged after the dive with air decompression (AD) as well as with O2 decompression (OD). A significant reduction in arterial PO2, on average 20 Torr, was found after the dive with AD. DLCO was decreased in all divers 20, 40, 60, and 80 min after diving with AD (P < 0.001), whereas it was not significantly decreased after diving with OD. Maximal DLCO decrease of approximately 15% occurred 20 min postdive. In AD diving, maximum bubble grade for each individual vs. maximum DLCO reduction correlated significantly (r = 0.85, P = 0.002), as well as DLCO vs. arterial PO2 (r = 0.64, P = 0.017). In conclusion, a reduction in pulmonary diffusing capacity is observed in parallel with the appearance of venous bubbles detected by precordial Doppler. We suggest that bubbles cause pulmonary microembolization, triggering a complex sequence of events that remains to be resolved. Measuring DLCO complements Doppler bubble detection in postdiving assessment of pulmonary function. PMID- 8444736 TI - Disappearance of palmitic acid from plasma of fetal and newborn sheep. AB - These studies were undertaken to measure the kinetic constants that characterize the disappearance of a representative free fatty acid (FFA) from the plasma of fetal and newborn sheep. A bolus of albumin-complexed [14C]palmitic acid was infused intravenously, and during the next 8 min, 24 arterial samples were collected to characterize the disappearance curve. Palmitic acid disappearance from plasma was well described by a double-exponential model. When birth was simulated in utero, kinetic values were not changed by cooling. However, after intrauterine ventilation with O2, the volume of distribution of the FFA increased 29%, its plasma clearance rate decreased 26%, and its apparent half-life in the plasma lengthened from 0.8 to 1.2 min (all P < 0.01, n = 8). After umbilical cord occlusion, plasma clearance rate decreased a further 19% and half-life lengthened to 1.4 min. About 60% of the increase in FFA concentration during simulated birth is explained by increased release from adipose stores, and 40% is explained by decreased clearance. Further experiments tested the influence of FFA concentrations themselves. After infusion of unlabeled FFA, clearance of the tracer decreased 23% (P < 0.05, n = 5), a result consistent with a saturable membrane transporter of FFAs. PMID- 8444737 TI - Delayed poststimulus decrease of phrenic motoneuron output produced by phrenic nerve afferent stimulation. AB - The immediate effects of phrenic afferent nerve activation on ventilation have been shown to be both excitatory and inhibitory. Long-lasting inhibitory effects on respiratory motoneuron output have been reported after stimulation of afferent nerves from limb muscles. However, whether respiratory muscle afferent nerves can produce this effect is unknown. We therefore hypothesized that activation of phrenic afferent nerves may produce a prolonged decrease of respiratory motoneuron output. Six alpha-chloralose-anesthetized dogs were studied after vagotomy and bilateral carotid sinus nerve section. The dogs were paralyzed, and end-tidal CO2 was controlled by mechanical ventilation. The proximal end of the cut thoracic phrenic nerve was electrically stimulated for 1 min at intensities that produced activation of thin-fiber afferents. The contralateral efferent phrenic integrated electroneurogram (ENG) was recorded. During stimulation, phrenic ENG activity increased. ENG activity was recorded during recovery and reached a peak decrease compared with control of 19 +/- 11% (SD) 9.0 +/- 6 min after stimulation and returned to control after 30 min. A qualitatively similar response was seen after stimulation of the gastrocnemius nerve. We conclude that activation of thin-fiber afferents in the phrenic nerve can produce a delayed and prolonged decrease of respiratory motoneuron output similar to that of limb muscle afferent nerves. PMID- 8444738 TI - Response of genioglossus EMG activity to passive tilt in men. AB - Increased blood pressure (BP) leads to inhibition of respiratory activity of hypoglossal nerve in anesthetized cats, implying that arterial baroreceptor activity may inhibit upper airway motor outputs. We examined the effect of passive tilt on upper airway muscle activity in men under the assumption that changes in degree of tilt would change local pressure at the carotid baroreceptors. We also examined the possibility that inhibition of upper airway muscle activity occurred secondary to a decrease in level of arousal. In seven normal awake adult males, we measured electromyogram activity of the genioglossus (EMGge), electroencephalogram (EEG), electrocardiogram, ventilation, end-tidal fractional concentration of CO2, and BP while the subject was on a tilt table wearing inflatable antishock pants. Three tilt table positions were used: 60 degrees head-up (60 degrees increases), supine (S), and 30 degrees head-down (30 degrees decreases), with pants either deflated (P-) or inflated (P+) to 40 mmHg. During P-, moving the subject from 60 degrees increases to S to 30 degrees decreases positions resulted in steady-state heart rates of 94.8 +/- 1.7, 66.9 +/ 0.7, and 68.9 +/- 0.8 beats/min and EMGge activities of 54.4 +/- 4.4, 37.7 +/- 2.0, and 31.5 +/- 2.4% of maximum, respectively. During P+, changes in heart rate were similar but significantly reduced from P-, and positional changes in EMGge were eliminated. The level of arousal was unchanged. The transient response of EMGge to tilt was biphasic: when moving from upright to supine position, there was a rapid increase in activity during the tilt maneuver followed by a progressive decline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444739 TI - Thermoregulatory responses to hyperthermia during isoflurane anesthesia in humans. AB - The authors tested the hypotheses that isoflurane anesthesia increases the threshold for sweating but minimally decreases the gain (sensitivity) or maximum intensity of this response and that thermoregulatory responses to hyperthermia are similar in anesthetized men and women. Sweating in response to core hyperthermia was studied in five men and five women during 0, 0.8, and 1.2% end tidal isoflurane anesthesia. Thigh sweating was quantified by measuring gas flow, relative humidity, and temperature passing over a known surface area. The distal esophageal temperature triggering sweating was considered the sweating threshold, and gain was defined as the core temperature increment required to increase sweating rate from 25 to 75% of maximum observed intensity. The sweating threshold increased linearly with isoflurane concentration from 36.6 +/- 0.1 to 38.1 +/- 0.1 degrees C in the men and from 37.1 +/- 0.3 to 38.3 +/- 0.2 degrees C in the women. The thresholds were significantly higher in women than in men. Gain and maximum sweating intensities were similar at each anesthetic concentration and in men and women. These data indicate that isoflurane anesthesia significantly increases the threshold triggering thermoregulatory sweating but that gain and maximum sweating rate are relatively well preserved. PMID- 8444740 TI - Breathing, transcutaneous blood gases, and CO2 response in SIDS siblings and control infants during sleep. AB - Age-related changes of 20 variables describing breathing patterns, transcutaneous blood gases, and estimated CO2 response during sleep were examined in a cross sectional study of 30 healthy control infants and 150 healthy siblings of sudden infant death syndrome victims within the first 18 mo of life. Whole-night measurements were performed using noninvasive respiratory induction plethysmography and transcutaneous blood gas electrodes. Each candidate for the study was extensively screened and found to be healthy. Mean transcutaneous PCO2 (PtcCO2, median 40.3 Torr) and maximum PtcCO2 (median 44.8 Torr), as well as the estimated ventilatory response to inhalation of 2% CO2 in air during regular breathing, causing a 20-36% increase of ventilation per Torr PtcCO2, were not related to postnatal age. In contrast, paradoxical breathing decreased from 49.5 to 0% of total sleep time (TST), periodic breathing from 5.5 to 0% TST, and respiratory rate during regular breathing from 40 to 22 breaths/min; the portion of regular breathing increased from 32 to 55% TST and mean and minimum transcutaneous PO2 from 65.4 and 47 to 69.7 and 52 Torr with increasing stability. The largest changes occurred in the first 6 mo of life. Maximum apnea duration (9.5 s, maximum 16 s), mean apnea duration (3.74 s, breathing pauses > or = 2 s), and time spent apneic per hour of irregular breathing (199 s/h) were not related to age. The comparison of data from siblings and controls showed similarities in the above-mentioned variables. No significant differences were found among the groups. Also a comparison of 30 pairs of siblings and controls, matched for age, gender, birth, and actual body weight, did not show significant differences. The present study extends the knowledge of development of breathing control beyond the first 6 mo of life. PMID- 8444741 TI - A superior method for single cell dispersal of rat and tumorous human anterior pituitary tissue. PMID- 8444742 TI - Cultures of bovine tracheal epithelium with differentiated ultrastructure and ion transport. AB - Tracheal epithelial cells were grown on Nuclepore filters coated with human placental collagen. When grown immersed in medium containing fetal bovine serum, cells displayed an undifferentiated ultrastructure (no cilia and a cell height of approximately 10 microns). Short-circuit current (Isc) was approximately 1/10 that of the native epithelium. By contrast, when grown in hormonally defined, serum-free medium with an air interface, cells showed Isc equal to or greater than the original tissue, possessed cilia, and had a cell height of approximately 50 microns. Responses in Isc to mediators were similar to those of the original tissue, but differed from those of dog or human tracheal epithelium. Given the ready availability and low cost of the native tissues, bovine tracheal cultures grown in serum-free medium with an air interface should prove useful in studies of airway epithelial physiology. PMID- 8444743 TI - Organ-specific change in Dolichos biflorus lectin binding by myocardial endothelial cells during in vitro cultivation. AB - Endothelial cells of the NMRI mouse strain express a cell surface glycoprotein recognized by the lectin Dolichos biflorus agglutinin (DBA). This study documents a marked organ-specific increase in DBA-specific lectin binding of myocardium derived endothelial cells (MEC) of the NMRI/GSF mouse during in vitro cultivation. An up to 20-fold increase in DBA binding sites is observed in long term culture, an increase not found in other NMRI-derived endothelial cell lines (e.g., brain, aorta). The increase appears restricted to DBA in that binding with other lectins (PNA, WGA) was unaltered. NMRI MEC cultures maintain typical endothelial cell attributes such as cobblestone morphology on confluence, expression of endothelial cell-specific surface markers, and production of angiotensin-converting enzyme. Cultures routinely become aneuploid within 4 passages, several passages before upregulation of the DBA binding site(s). Myocardial endothelial cells sorted to obtain DBAhi and DBAlo cell populations generally maintained their sorted phenotype for 3 to 4 passages. Limiting dilution cloning resulted in clones varying in DBA expression. Clones for DBAhi expression maintained their DBA affinity for at least 10 passages (> 30 doublings), whereas DBAlo clones gave rise to varying numbers of DBAhi cells within 2 to 4 passages. We hypothesize that the change in DBA affinity accompanies in vitro aging, that the change is independent of alterations in karyotype, and that the increase in DBA affinity may reflect a change in one or more other endothelial cell properties. Additional studies will be necessary to determine whether the in vitro changes are correlated with specific functional alterations and whether they accurately reflect progressive changes of MEC in vivo. PMID- 8444744 TI - Fibroblast inhibition of tumor cells may be mediated by TGF-beta 1. PMID- 8444745 TI - Differentiation of isolated murine embryonic palatal epithelium in culture: exogenous transforming growth factor alpha modulates matrix biosynthesis in defined experimental conditions. AB - A novel culture technique, which supports the growth and differentiation of mouse embryonic palatal epithelial cells in the absence of either an extracellular matrix substratum or feeder layers, has been developed. Using this technique we have investigated the effects of exogenous transforming growth factor alpha (TGF alpha) and serum on extracellular matrix biosynthesis by primary cultures of mouse embryonic epithelial sheets under defined experimental conditions. In all culture treatments (chemically defined medium with and without TGF alpha or serum) the palatal epithelial sheets differentiated into three regionally distinct cell phenotypes after 36 h. Nasal and oral cells differentiated into pseudostratified, ciliated columnar, and stratified squamous keratinizing epithelium, respectively. In addition, basal medial edge epithelial (MEE) cells at the oral/nasal regional interface assumed an elongated cobblestoned phenotype. In serum-free medium, collagen types IV and V, laminin, fibronectin, and heparan sulphate proteoglycan were detected immunocytochemically throughout the entire epithelial sheet. Tenascin and collagen IX were present almost exclusively in MEE cells. Types I, II, and III collagen were completely absent. Addition of TGF alpha or serum universally increased the intensity of staining, most notably that for tenascin and collagen IX in MEE cells. These results indicate that mouse embryonic palatal epithelial sheets can be maintained under defined culture conditions during which they exhibit patterns of differentiation similar to those observed in vivo. TGF alpha, known to localize to the MEE in vivo, can modulate palatal extracellular matrix biosynthesis, particularly by the MEE, suggesting a regulatory role for this factor. The culture system is suitable for further investigating the effects of exogenous factors on mouse embryonic palatal epithelial cell bioactivity and differentiation. PMID- 8444746 TI - Transient induction of cytochrome P450 1A1 mRNA by culture medium component in primary cultures of adult rat hepatocytes. AB - Because the metabolic environment can alter gene expression in cultured cells, we examined the effects of change of medium on the levels of several cytochrome P450 mRNAs in primary cultures of rat hepatocytes maintained on Matrigel. The amounts of P450 1A2, 2B1/2, or 3A1 mRNA were unaffected by changing the medium. In contrast, P450 1A1 mRNA levels were increased 1 to 2 h after media change, reached maximum levels by 6 h, and declined to baseline by 24 h. Supplementing day-old media with components of the medium revealed that only addition of amino acids resulted in 1A1 mRNA induction. From the results of direct additions and omissions, we showed that tryptophan, but not histidine, was largely responsible for the 1A1 mRNA induction. Moreover, mild photoactivation of the tryptophan resulted in a substantially increased magnitude of 1A1 mRNA induction. The time course for 1A1 mRNA induction by treatment with photoactivated tryptophan was identical to that observed after medium change. Treatment of hepatocyte cultures with beta-naphthoflavone, which is metabolized by 1A1, also resulted in a transient 1A1 mRNA induction time-course profile over a 24-h period, whereas treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin, which is relatively stable to metabolic transformation, produced sustained elevations of 1A1 mRNA, suggesting that the transient response to tryptophan also may involve metabolism of the inducer. Our results extend previous data showing that oxidized products of tryptophan induce 1A1, and suggest that the transient nature of the induction may be due to elimination of the activated tryptophan molecule. PMID- 8444748 TI - Arkansas HIV/AIDS report 1983-1993. PMID- 8444747 TI - Transforming growth factor-beta: signal transduction via protein kinase C in cultured embryonic vascular smooth muscle cells. AB - Transforming growth factor-beta (TGF-beta), an ubiquitous regulatory peptide, has diverse effects on the differentiation and behavior of vascular smooth muscle cells (VSMC). However, the molecular mechanism through which TGF-alpha exerts its effects remains obscure. We investigated the phosphoinositide/protein kinase C [PKC] signaling pathway in the action of TGF-beta on cultured embryonic avian VSMC of differing lineage: a) thoracic aorta, derived from the neural crest; and b) abdominal aorta, derived from mesenchyme. The second messenger responsible for activation of PKC is sn-1,2-diacylglycerol [DAG]; TGF-beta increased the mass amounts of DAG in the membranes of neural crest-derived VSMC concurrent with translocation of PKC from the soluble to the membrane fraction, but TGF-beta had no effect on the DAG or PKC of mesenchyme-derived VSMC. TGF-beta potentiated the growth of platelet-derived growth factor (PDGF)-treated, neural crest-derived VSMC; but abolished PDGF-induced growth of mesenchymal cells. It is concluded that molecular and functional responses of VSMC to TGF-beta are heterogeneous and are functions of the embryonic lineage of the VSMC. PMID- 8444749 TI - Electrocardiogram of the month. PMID- 8444750 TI - Radiological case of the month. Inadvertant guidewire entrapment by IVC filter during subclavian line placement. PMID- 8444751 TI - The psychosocial functioning and family environment of depressed adolescents. AB - OBJECTIVE: This study examined measures of functional impairment and family relations in a sample of 62 adolescents with major depressive disorder (MDD) and 38 normal controls with no history of psychiatric illness. METHOD: Ratings of the following domains were obtained: mother-child relations, father-child relations, spousal relations, sibling relations, peer relations, and school performance. Ratings of each domain for the 3-month period preceding the assessment were derived from information obtained using a semistructured interview administered independently to the adolescents and one of their parents. RESULTS: Adolescents with MDD were found to have severe difficulties in all areas. Ninety percent of the depressed adolescents had scores greater than 2 SD above the mean of the normal controls on one or more of the domain ratings. In addition, adolescents with difficulties in parent-child relations were more likely than those adolescents without problems in family relations to have difficulties in peer relations and school performance. CONCLUSIONS: The authors discuss the importance of systematically examining psychosocial variables in future studies of the etiology, course, and treatment of MDD in adolescents. PMID- 8444752 TI - Comparison of preventive interventions for families with parental affective disorder. AB - Twenty families participated in a random assignment trial of two cognitive psychoeducational preventive interventions for families with parental affective disorder. Twelve families were assigned to a clinician-based intervention and eight to a lecture-based intervention, with assessment prior to intervention and an average of 18 weeks following intervention. Both groups were satisfied and believed they received help from the intervention. The clinician-based group was significantly more satisfied overall, and reported significantly more changes in both behaviors and attitudes about their illness from pre- to postintervention. Both groups showed significant decrease in degree of upset over issues of concern from pre- to postintervention. The clinician-based group reported receiving significantly more help with their primary concern. The implications of these findings are discussed. PMID- 8444753 TI - Parental reports of seasonal mood and behavior changes in children. AB - OBJECTIVE: The chief purpose of this study was to investigate the nature and prevalence of children's seasonal symptoms. METHOD: Parental reports of seasonal changes in six mood or behavioral symptoms (sleeping, eating, irritability, energy, withdrawal, and sadness) were surveyed for children living across the United States. The sample included 892 girls (mean age = 10.5 +/- 1.0 years) and 788 boys (mean age = 10.6 +/- 0.9 years), with a response rate of 46% for girls' parents and 39% for boys' parents. RESULTS: At least one winter recurring symptom was reported in 48.5% of children, as compared with 9.1% in fall and 10.8% in spring. Winter symptoms were reported equally in girls and boys with one exception ("is tired"); age effects were found for three symptoms only in girls ("sleep more," "is tired," and "withdraws"). Regional effects showed more winter symptoms reports in northern zones than in southern zones. CONCLUSIONS: Given the potential therapeutic benefit of light therapy in children with such seasonal patterns, careful assessment of seasonality is merited for children with winter mood and behavior problems. PMID- 8444754 TI - A retrospective study of serum levels and electrocardiographic effects of nortriptyline in children and adolescents. AB - OBJECTIVE: We retrospectively evaluated a large pediatric population treated with nortriptyline (NT) in an outpatient psychopharmacology clinic to assess pharmacokinetic and electrocardiographic (EKG) effects. METHODS: A systematic search revealed 82 children and adolescents treated naturalistically with NT. All patients with available EKGs and serum NT levels were included in the series with the exception of those receiving concomitant antipsychotic agents. Forty-three percent of subjects were receiving medications in addition to NT. RESULTS: Patients received an average (+/- SE) NT dose of 2.0 +/- 0.1 mg/kg yielding mean serum NT levels of 105.5 +/- 7.4 ng/mL. There was a linear relationship of NT dose (mg/kg) to serum NT levels (r = 0.50, p < 0.0001). NT treatment resulted in small increases in heart rate, and PR, QRS, and QTc intervals (all ps < 0.01), of similar magnitude in children and adolescents. Individuals with the highest baseline EKG indices had the least amount of change in those indices with NT treatment. There were only a few statistically significant associations between NT dose or serum NT levels and EKG parameters. NT treatment was significantly associated with the onset of asymptomatic sinus tachycardia (heart rate > 100 beats per minute), and prolongation of the EKG QRS (> 100 msec) and QTc (> 440 msec) intervals. CONCLUSIONS: These findings suggest: (1) NT has a predictable dose to level relationship, (2) the effect of NT on the EKG in this age group is mild and similar to that reported with other tricyclic antidepressants, and (3) there are few age-specific differences in NT-induced EKG changes. PMID- 8444755 TI - Representations of attachment in mothers and their one-year-old infants. AB - Attachment classifications in mothers and their 1-year-old infants were independently and concurrently assessed using the Adult Attachment Interview and the Strange Situation Procedure. Overall concordance was significant (k = 0.62), with strong links apparent between mothers classified dismissing and infants classified avoidant and between mothers classified autonomous and infants classified secure. Mothers' classified preoccupied were not more likely to have infants classified resistant. Mothers' perceptions and interpretations of the emotional distress of an infant observed in a 4-minute videotape were related to both infant and mother attachment classifications. These results are compatible with the suggestion that attachment classification reflect differences in internal working models of relationships. Other measures of maternal psychosocial adjustment were not related to infant attachment classifications. PMID- 8444756 TI - Longitudinal relations between temperament traits and behavioral syndromes in middle childhood. AB - OBJECTIVE: This study tested Graham and Stevenson's 1987 hypothesis specifying links between EAS (emotionality-activity-sociability) temperament traits and behavioral syndromes of depression, hyperactivity, and delinquency in an unselected sample of 164 children in infancy and early childhood. METHOD: Mothers completed the Colorado Child Temperament Inventory. Each mother also used the Child Behavior Checklist (CBCL) to report on her child's behavior problems after the child's completion of first grade. Scores on three CBCL scales, anxiety/depression, attention problems, and delinquent behavior, were examined in relation to the EAS traits. RESULTS: For boys, high emotionality in infancy and early childhood was associated with high scores on both the anxiety/depression and attention problem scales. For girls, both high emotionality and low sociability predicted high scores on the anxiety/depression scale. There were no associations between EAS traits and attention problems for girls. There was little evidence for links between EAS traits and delinquent behavior for either boys or girls. CONCLUSIONS: The results are discussed with respect to temperamental traits as risk factors for the emergence of behavior problems in childhood. PMID- 8444757 TI - Sex differences in psychological adjustment from infancy to 8 years. AB - The objective of this study was to explore sex differences in development from infancy to 8 years of age in a community sample. Measures of biological, social, interactive, and parental functioning as well as teacher reports were obtained. There were minimal differences in infancy, but major psychosocial differences emerged with increasing age. In the biological sphere boys were disadvantaged only in ratings of language and motor skills at 3 to 4 years old. They showed greater temperamental "difficulty" and low persistence factor scores from 5 years onward. Boys were significantly more likely to have problems with adaptive behavior and social competence and to show behavior problems of the hyperactive and aggressive type, as rated by mothers. Parent and family functioning measures did not differentiate between the sexes. Teachers rated boys as having more problems in academic and behavioral domains the first 3 years of school. Path analyses combining data sets gathered when the children were 3 to 8 years old demonstrated the differential courses of development for boys and girls although temperamental flexibility was the best predictor of behavioral adjustment for both sexes. A social learning explanation of the increased incidence of problems among males is supported, although biological influences are not ruled out. PMID- 8444758 TI - The prevalence of gender-atypical behavior in elementary school children. AB - OBJECTIVE: To supplement the few small-scale studies on convenience samples of boys with an epidemiological study on the prevalence of gender-atypical behaviors (GABs) in boys and girls and to assess the influence of variation of age, ethnicity, and socioeconomic status. METHOD: The present study, a postal questionnaire survey, used an existing pool of GAB items for boys, developed comparable GAB items for girls, and analyzed parent-reported frequencies of GABs in a demographically heterogeneous community sample of 687 boys and girls age 6 to 10 years. RESULTS: The majority of GABs were quite rare, but there was considerable variability in their prevalence. Nevertheless, many children show multiple GABs although each individual GAB at low frequency; for instance, 10 or more different GABs were exhibited by 22.8% of boys and 38.6% of girls. Only few GABs varied significantly with age, ethnicity, or socioeconomic status. CONCLUSIONS: These data are of relevance to clinicians counseling parents who are worried about the occurrence of GABs in their children. PMID- 8444759 TI - Diagnoses of attention-deficit hyperactivity disorder from parent reports predict diagnoses based on teacher reports. AB - OBJECTIVE: For DSM-III attention deficit disorder (ADD), it was previously reported that, when a parent report leads to a diagnosis of ADD, it is highly likely that the teacher report will also be positive. This report seeks to generalize that finding to DSM-III-R attention-deficit hyperactivity disorder (ADHD). METHOD: In a population of 34 children meeting clinical criteria for DSM III-R ADHD, parents and teachers independently responded to questions about individual ADHD symptoms. RESULTS: Correlations between parents and teachers for individual symptoms were low to moderate; however, there was a 77% probability that the teacher report would result in a positive diagnosis given a positive parent diagnosis. This probability increased to 88% if "broad" teacher diagnoses of ADHD, defined by 35% of the 14 DSM-III-R symptoms, were included. CONCLUSIONS: In clinically-referred children, a clinical diagnosis of ADHD based on parent report is likely to be corroborated by a teacher report. PMID- 8444760 TI - Effects of emotion on perceptual asymmetry in adolescent inpatients with attention-deficit hyperactivity disorder. AB - OBJECTIVE: The authors studied the hemispheric functioning of adolescents with attention-deficit hyperactivity disorder (ADHD) in relation to this group's response to positively toned emotional stimuli. METHOD: Dichotic word tests were used to measure perceptual asymmetry in 21 adolescent inpatients and 24 control subjects. Ten patients had ADHD; 11 did not. Subjects were tested under four emotional conditions by using combinations of neutral, positive, and negative words. RESULTS: the ADHD group had lower right ear advantage (REA) scores when presented with stimulus pairs containing positive words than when presented with pairs not containing positive words. By comparison, the non-ADHD patient group and the control group had higher REA scores under positive emotional conditions than under non-positive conditions. CONCLUSIONS: The abnormal response to positive emotional tone supports the reward system dysfunction hypothesis of ADHD and may also have implications for learning problems, behavioral difficulties, and disturbed interpersonal relationships in this population. PMID- 8444761 TI - The adolescent outcome of hyperactive children: predictors of psychiatric, academic, social, and emotional adjustment. AB - OBJECTIVE: To investigate predictors of adolescent outcome in a large sample of hyperactive children. METHOD: 123 hyperactive children were followed prospectively over an 8-year period. Multiple linear and logistical regression equations were used to relate childhood predictor variables to adolescent academic, psychiatric, social, and emotional adjustment. RESULTS: Adolescent academic skills were related to childhood cognitive and academic competence while school conduct was predicted by other variables including early family stress. Duration of mental health treatment received often was negatively related to outcome, apparently serving as a marker variable for severity of disturbance in the child. Childhood impulsivity-hyperactivity and paternal antisocial acts were associated with later oppositional-defiant behaviors. Only child defiance and not hyperactivity predicted later arrests, however. Emotional problems in adolescence were predicted by more special education enrollment. Adolescent social competence was associated with parental personal competence, whereas maternal mental health status at outcome was related to variables unassociated with child adjustment. CONCLUSIONS: Various outcome domains had different sets of predictors; no single predictor cut across all domains. Although a limited amount of variance in outcome was explained, findings suggest that promoting family and parental competence as well as assessing and treating defiance and aggression very early may improve outcome. PMID- 8444762 TI - Methylphenidate and desipramine in hospitalized children: I. Separate and combined effects on cognitive function. AB - OBJECTIVE: The separate and combined effects of methylphenidate and desipramine on cognitive function were investigated in 16 psychiatrically hospitalized children with primary, secondary, and mixed features of attention-deficit hyperactivity disorder and mood disorder. METHOD: A double-blind, placebo controlled, crossover design was used to investigate drug effects on vigilance, short-term memory, visual problem solving, and higher-order learning. RESULTS: Methylphenidate alone improved vigilance, both drugs positively affected short term memory and visual problem solving, and combined drugs affected learning of higher-order relationships. CONCLUSIONS: Separate and combined drug effects are related to the specific cognitive domain assessed and have implications for neurotransmitter models of action. PMID- 8444763 TI - Nortriptyline in the treatment of ADHD: a chart review of 58 cases. AB - OBJECTIVE: The potential benefit of the tricyclic antidepressant medication, nortriptyline (NT), in the treatment of children and adolescents with attention deficit hyperactivity disorder (ADHD) was evaluated. METHOD: A systematic search was conducted from a computerized data base of all clinic patients in an outpatient pediatric psychopharmacology unit treated with NT for ADHD. The records of the 58 subjects identified (37 children and 21 adolescents) were reviewed for overall response, dose, serum levels, and adverse effects. RESULTS: Ninety-seven percent of the identified subjects had failed to respond to an average of four previous medication trials, 84% had at least one comorbid diagnosis with ADHD, and 47% were receiving at least one concurrent medication. NT doses ranged from 0.4 to 4.5 mg/kg (X +/- SD = 2.0 +/- 1.0 mg/kg) and subjects received NT from 0.4 to 57.9 months (11.9 +/- 14.0 months). Overall, 76% of subjects were considered to have a moderate to marked improvement by an independent rater, which was corroborated by their clinicians. There was no association between response and age, rate of comorbidity, number of previous medication trials, or concurrent pharmacotherapy (all p NS). Although there were no overall differences in serum NT levels between responders and nonresponders, significantly more patients within the suggested therapeutic range in adults of 50 to 150 ng/ml were classified as "markedly improved" than those outside this range (68% versus 35%, p < 0.03). Mild adverse effects were reported in 20 subjects (34%). CONCLUSIONS: These findings suggest that NT may be an effective well-tolerated agent for ADHD children and adolescents. Additional controlled investigations utilizing NT for ADHD should be undertaken. PMID- 8444764 TI - Comparison of clonidine response in the treatment of attention-deficit hyperactivity disorder with and without comorbid tic disorders. AB - OBJECTIVE: Clonidine has been suggested as an alternative pharmacotherapy for patients with attention-deficit hyperactivity disorder (ADHD) and comorbid tic disorders. To examine the efficacy of clonidine in this population of children, the use of clonidine in the treatment of children with ADHD with and without comorbid tic disorders was examined in a retrospective chart review of 54 children over a 4-year period. METHOD: Treatment was administered openly to these patients in a Pediatric Psychopharmacology Clinic, and response was assessed using clinical global improvement measures. RESULTS: Clonidine treatment resulted in improvement in both the ADHD (39/54; 72%) and tic symptoms (18/24; 75%) groups. The findings suggested that the children with ADHD with comorbid tic disorders (23/24; 96%) have a more frequent positive behavioral response to clonidine than children with ADHD without comorbid tic disorders (16/30; 53%). CONCLUSIONS: This report provides further support of a role for clonidine in the treatment of children with ADHD, particularly for those with comorbid tic disorders. PMID- 8444765 TI - Desipramine treatment of children with attention-deficit hyperactivity disorder and tic disorder or Tourette's syndrome. AB - OBJECTIVE: As many as 50% of patients with Tourette's syndrome (TS) also meet diagnostic criteria for attention-deficit hyperactivity disorder (ADHD). Since antipsychotics are of limited value in controlling the symptoms of ADHD and stimulants can exacerbate tics, alternative treatments are directly needed. The purpose of this study was the examination of the efficacy of desipramine (DMI) in the treatment of pediatric patients with chronic tic disorder (CTD; TS or chronic motor tics) + attention-deficit hyperactivity disorder (ADHD). METHOD: All pediatric patients with the diagnosis of CTD that were treated with DMI were ascertained from retrospective systematic chart reviews of a psychopharmacology clinic and a neurology service specialized in movement disorders. RESULTS: Of the 33 identified patients, 30 had comorbid CTD + ADHD and three had CTD alone. In all, 82% had significant improvement in CTD symptomatology and 80% significantly improved ADHD symptoms without major adverse effects over an average follow-up period of 16 months. CONCLUSIONS: Although the conclusions from this retrospective report can be seen as preliminary only until replicated in a controlled investigation, the magnitude and persistence of the response is encouraging and suggest a therapeutic role for DMI in the treatment of CTD + ADHD patients. PMID- 8444766 TI - Patterns of diagnostic comorbidity in a community sample of children aged 9 through 16 years. AB - Secondary analyses of the data from the Puerto Rico Child Psychiatry Epidemiologic Study were done to provide information on the comorbidity of four major diagnostic domains (attention deficit disorders, conduct/oppositional disorders, depression and anxiety disorders). A high level of comorbidity was found among these four domains of child and adolescent psychopathology. In general the patterns of comorbidity were not affected by whether the data was put together by a clinician or by means of a computer algorithm scoring a structured interview. The patterns were not affected in any major way by who the informants were in the diagnostic process. Minor differences were found in certain comorbidity patterns depending on the sex and age of the subjects. Comorbidity was associated with level of impairment and to service utilization. PMID- 8444767 TI - Prevalence of psychiatric disorders in a community population of older adolescents. AB - In a community study of 386 Caucasian working-class older adolescents, a sizeable proportion met lifetime criteria for selected DSM-III-R diagnoses. Alcohol abuse/dependence had the highest lifetime prevalence rate (32.4%), followed by phobias (22.8%), drug abuse/dependence (9.8%), major depression (9.4%), and, least commonly, post-traumatic stress disorder (6.3%) and obsessive compulsive disorder (2.1%). Significant gender differences were found for major depression, post-traumatic stress disorder, and alcohol abuse/dependence, whereas socioeconomic differences occurred in major depression, phobias, and drug abuse/dependence. Adolescents with specific psychiatric disorders had significantly poorer functioning on measures of behavioral problems, interpersonal problems, self-esteem, and school performance. Results suggest the importance of identifying psychiatric disorder in adolescence, and the need for preventive strategies and prompt treatment. PMID- 8444768 TI - Rural-urban child psychopathology in a Northeastern U.S. state: 1986-1989. AB - Parent and teacher symptom reports from two epidemiological surveys of 2,519 Connecticut children were used to study rural-urban differences in childhood psychopathology. Parents and teachers of girls in cities reported elevated total disturbance and social withdrawal. Parents of urban girls also reported higher rates of behavioral disturbance. For boys, urban excesses were primarily observed in emotional disturbance. Rural-urban variation was largely associated with economic and cultural differences between sites and not with urbanization per se. Findings suggest that certain assumptions about rural-urban differences in specific forms of psychopathology, such as delinquency, should be reevaluated. PMID- 8444769 TI - Pathways of problem behaviors from childhood to adolescence. AB - OBJECTIVE: the purpose of this study was to determine the 6-year longitudinal course of psychiatric disorders in children from the general population commencing at age 4 to 11 years. METHOD: three groups of children were selected on the basis of Child Behavior Checklist ratings obtained at 2-year intervals: "persisters," "decreasers," and "increasers." Selected subjects and their parents were clinically interviewed, and DSM-III-R diagnoses were derived. RESULTS: the majority of children whose overall level of psychopathology persisted over time obtained lifetime DSM-III-R diagnoses classified as externalizing: attention deficit hyperactivity disorder, oppositional disorder, or conduct disorder. The majority of children whose overall level of psychopathology decreased obtained lifetime DSM-III-R diagnoses classified as internalizing: anxiety disorders, major depression, or dysthymic disorder. Children with initial Child Behavior Checklist scores in the normal range whose problem scores increased received lifetime diagnoses that were neither predominantly externalizing or internalizing. CONCLUSIONS: this study showed that the majority of initially disordered children with the poorest outcome showed aggressive or antisocial behaviors, whereas disordered children whose functioning improved had problems reflecting fearful, inhibited, or depressive behavior. The findings also showed that retrospective information on the course of children's problem behaviors should be regarded with caution. PMID- 8444770 TI - Scales, diagnoses, and child psychopathology: I. CBCL and DISC relationships. AB - OBJECTIVE: To clarify the relationship between scales and structured diagnostic interview diagnoses, the authors used a two-stage screening method to study 201 military families with one or more children ages 5 to 17. METHOD: Parents and children were interviewed with the Diagnostic Interview Schedule for Children (DISC 2.1); parents also completed the Child Behavior Checklist (CBCL) while the children completed other self-report symptom scales. RESULTS: Results indicate only a modest ability of scales to discriminate among discrete DISC-derived DSM III-R diagnoses. Inclusion of diagnostic information from both parents and children resulted in more diagnoses than from either informant alone, and the additional diagnoses consisted mostly of internalizing disorders contributed by child-derived DISC information. In general, correlations were larger between scales and diagnoses within the same informant (regardless of diagnostic construct) than across informants (but within the same diagnostic construct). Child self-report measures tended to outperform the CBCL as screeners against the overall "caseness" criterion on the DISC. However, child self-report scales were relatively nonspecific and showed little ability to selectively identify internalizing disorders such as anxiety and/or depression. Compared with single informant diagnoses, combined-informant diagnoses were generally superior in demonstrating broader relationships to both parent and child symptom scales. CONCLUSIONS: Additional research is needed in order to build careful crosswalks between the various approaches to assessing childhood psychopathology, to decide on optimal rules for combining information to establish diagnoses, and to validate the currently available assessment alternatives. PMID- 8444771 TI - Do Caucasian and black adolescents differ at psychiatric intake? AB - A large sample of adolescents brought for psychiatric evaluation to a public University based facility are the subjects of the study. Material incorporated in a DSM-III multiaxial formulation plus symptoms constituted the dependent variables. Analyses concentrated on ethnic differences, with variation associated with gender and social class controlled statistically. Caucasians showed comparatively greater clinical morbidity: higher number of Axis I definite diagnoses and level of symptoms. Eating disorder diagnoses were more common in Caucasians. There were no significant differences pertaining to level of stress or social impairment. Blacks showed higher levels of symptoms scored as "social aggression" and diagnosed as conduct disorders. The pattern of results raised the question of a possible referral bias, with blacks shunted to the psychiatric facility with lower levels of standard clinical psychopathology, but higher levels of social oppositional behavior. Further research is needed to verify if such a bias does exist. PMID- 8444772 TI - Premigratory expectations and mental health symptomatology in a group of Vietnamese Amerasian youth. AB - This paper reports on the first phase of a prospective longitudinal evaluation of the relationship between premigratory expectations for life in the United States and postmigratory symptoms of anxiety and depression in a group of Vietnamese Amerasian youth. Premigratory expectations, as measured by an expectations questionnaire, are correlated with concurrent symptomatology assessed utilizing the General Health Questionnaire, Hopkins Symptom Checklist-25, and Vietnamese Depression Scale. Those with higher premigratory expectations tended to report fewer symptoms of anxiety and depression. Implications of these findings for future research defining the relationship between premigratory expectations and postmigratory symptoms are discussed. PMID- 8444773 TI - Violent events reported by normal urban school-aged children: characteristics and depression correlates. AB - OBJECTIVE: This paper reports data on the prevalence of morbid thoughts of death or injury and the experiences of violence for a sample of 6 to 12 year old urban school children and examines the relationship of these thoughts and experiences to the child's emotional health. METHOD: Fifty-seven of the sample of 223 children who attended the same inner-city school described violent events occurring to themselves, a relative or friend. All children were interviewed and assessed on the Children's Depression Rating Scale-Revised (CDRS-R). RESULTS: Significantly higher CDRS-R sum scores, indicating the presence of suspected depression or of clinical concern, were recorded for the 57 children reporting experiences with violence. As well, the subgroup of 57 children were significantly more distressed by specific symptoms of low self-esteem, weeping, and worries about death or injury. CONCLUSIONS: Finding so many children reporting violent events occurring in their homes and community and that these children's experiences of violence were associated with emotional disturbances such as depression, dysphoric mood, low self-esteem, and excessive fears and worries about death or injury suggests the need for routine examination of the history of exposure to violence in the evaluation of inner-city children. PMID- 8444774 TI - The prevalence and consequences of exposure to violence among African-American youth. AB - The objective of this study was to examine the relationship between chronic exposure to community violence and post-traumatic stress disorder (PTSD) symptoms in a nonrandom sample (N = 221) of low-income African-American youth between 7 and 18 years old. Results showed males were more likely than females to be victims of and witnesses to violent acts; there were no other significant sociodemographic differences in the degree of exposure to violence. PTSD symptom reporting was moderately high for this sample of youth; 54 youth (27.1%) met all three of the diagnostic criteria considered. Regression analyses revealed that being victimized and witnessing violence were significantly related to the reporting of PTSD symptoms. These symptoms were more extreme among victimized females and victimized youth who had no primary males living with them in the household (i.e., fathers and/or brothers). Exposure to violence among youth is clearly significant to their reporting of PTSD symptomatology, yet the clinical implications of this relationship remain largely unexplored. PMID- 8444775 TI - A 6-year follow-up study of Cambodian refugee adolescents traumatized as children. AB - Seventy-three percent of a sample of 46 Cambodian youth interviewed in 1984 and 1987 were reinterviewed in 1990 as part of a pretest for a multisite study of Cambodian refugee trauma now under way. An additional sample of convenience of 38 youth were also interviewed to determine reliability and validity of the diagnostic instruments chosen for the larger study. The DSM-III-R diagnosis of post-traumatic stress disorder (PTSD) was found to persist, but the symptoms appeared less intense over time. In contrast, the prevalence of depression dropped markedly since 1987. Subjects remained largely free of comorbid conditions. Diagnostic reliability and validity were satisfactory. The follow-up sample appeared to be functioning well despite their PTSD profiles. The findings are discussed in light of several current controversies surrounding the concept and measurement of PTSD. PMID- 8444776 TI - Industrial disaster and mental health of children and their parents. AB - OBJECTIVE: We report the findings of research conducted a year after an industrial disaster (PCB fire), which occurred on Montreal's South Shore in 1988. A total of 1,663 families were evacuated for a period of 18 days. The study evaluated 174 children between the ages of three and eleven years: 87 in the exposed group and 87 in the control sample. METHOD: Structured questionnaires were administered to the children and their mothers and fathers during home visits. RESULTS: Based on the responses of the children and the mothers, children aged 6 to 11 years displayed more overall internalized and post-traumatic stress disorder (PTSD) symptoms than did those in the control group. CONCLUSIONS: The study demonstrates that the mental health of fathers as well as mothers correlates with children's symptoms and that parents are able to accurately observe their child's reaction to a disaster. PMID- 8444777 TI - The role of a research seminar for child psychiatry residents. AB - A major problem confronting the field of child and adolescent psychiatry is the development of teaching strategies to stimulate research activities and an appreciation of research. A teaching approach is described which emphasizes major research concepts using a programmed instruction method and illustrating these concepts with clinical cases. Fourteen child psychiatry residents participated in the seminar during a 3-year period. Overall, trainees' evaluation of the seminar was positive, and they demonstrated a high level of understanding across major research topics. In addition, the seminar may have contributed to an increased preference for academic careers by graduating residents. PMID- 8444778 TI - Determinants of academic survival: survey of AACAP poster authors. AB - OBJECTIVE: To assess personal and institutional factors that may influence the development and retention of child psychiatry researchers and to estimate academic survival rates of full-time child psychiatry researchers. METHOD: One hundred forty-seven (79%) of 187 physician-first authors of research posters presented at the annual meetings (1984 to 1990) of the American Academy of Child and Adolescent Psychiatrists were surveyed for demographic data, current academic status, level of research involvement, career path from 1984 to 1991, and factors facilitating or hindering research career success. RESULTS: Survival analysis of strictly defined full-time researchers (N = 46) revealed a 67% 7-year survival rate. Significantly higher survival rates were obtained for investigators with more than 2 years of research training or with affiliation with major child psychiatric research institutions when beginning a full-time research position. Both these factors were significant and independent predictors of academic survival. CONCLUSIONS: Research training and affiliation with a major child psychiatric research institution are associated with longer academic survival for full-time researchers. PMID- 8444779 TI - Malpractice litigation against child and adolescent psychiatry residency programs, 1981-1991. AB - A national survey was conducted to investigate malpractice litigation at United States child and adolescent psychiatry residency programs between 1981 and 1991. Fourteen percent of the directors of child and adolescent psychiatry reported at least one malpractice claim during this period. The highest percentage of lawsuits reported was in the northeast. Suicide and sexual abuse of latency age patients by other patients accounted for the most litigation. The mean monetary award was $167,000, and the largest award was $500,000 for discharge of a patient who killed his mother. There has been an increase in malpractice litigation during the past 10 years. Risk management strategies should be implemented to address areas of liability in child and adolescent psychiatry training programs. PMID- 8444780 TI - Statistical case puzzle. The case of the despondent student. PMID- 8444781 TI - The effectiveness of psychotherapy. PMID- 8444782 TI - Limitations of structural interviews. PMID- 8444783 TI - Clonazepam for OCD. PMID- 8444784 TI - Ethics of animal research. PMID- 8444785 TI - Inhibition of Escherichia coli chemotaxis by omega-conotoxin, a calcium ion channel blocker. AB - Escherichia coli chemotaxis was inhibited by omega-conotoxin, a calcium ion channel blocker. With Tris-EDTA-permeabilized cells, nanomolar levels of omega conotoxin inhibited chemotaxis without loss of motility. Cells treated with omega conotoxin swam with a smooth bias, i.e., tumbling was inhibited. PMID- 8444786 TI - Characterization of the binding sites of two proteins involved in the bacteriophage P2 site-specific recombination system. AB - Integration of the bacteriophage P2 genome into the Escherichia coli host chromosome occurs by site-specific recombination between the phage attP and E. coli attB sites. The phage-encoded 38-kDa protein, integrase, is known to be necessary for both phage integration as well as excision. In order to begin the molecular characterization of this recombination event, we have cloned the int gene and overproduced and partially purified the Int protein and an N-terminal truncated form of Int. Both the wild-type Int protein and the integration host factor (IHF) of E. coli were required to mediate integrative recombination in vitro between a supercoiled attP plasmid and a linear attB substrate. Footprint experiments revealed one Int-protected region on both of the attP arms, each containing direct repeats of the consensus sequence TGTGGACA. The common core sequences at attP and attB were also protected by Int from nuclease digestion, and these contained a different consensus sequence, AA T/A T/A C/A T/G CCC, arranged as inverted repeats at each core. A single IHF-protected site was located on the P (left) arm, placed between the core- and P arm-binding site for Int. Cooperative binding by Int and IHF to the attP region was demonstrated with band-shift assays and footprinting studies. Our data support the existence of two DNA-binding domains on Int, having unrelated sequence specificities. We propose that P2 Int, IHF, attP, and attB assemble in a higher-order complex, or intasome, prior to site-specific integrative recombination analogous to that formed during lambda integration. PMID- 8444787 TI - Complete structure of the tyrosine-linked saccharide moiety from the surface layer glycoprotein of Clostridium thermohydrosulfuricum S102-70. AB - In this study, we have extended and completed a previous investigation (P. Messner, R. Christian, J. Kolbe, G. Schulz, and U. B. Sleytr, J. Bacteriol. 174:2236-2240, 1992) in which we demonstrated for the first time in prokaryotic organisms the presence of a novel O-glycosidic linkage via tyrosine. The surface layer glycoprotein of the eubacterium Clostridium thermohydrosulfuricum S102-70 is arranged in a hexagonal lattice, with center-to-center spacings of approximately 16.3 nm. Molecular weight determination by sodium dodecyl sulfate polyacrylamide gel electrophoresis of both glycosylated and chemically deglycosylated surface layer glycoprotein showed values for the monomeric subunits of 94,000 and 87,500, respectively. Glycopeptide fractions obtained after exhaustive pronase digestion of purified, intact glycoprotein were isolated by reversed-phase liquid chromatography. One- and two-dimensional nuclear magnetic resonance studies, together with chemical analyses and plasma desorption time-of-flight mass spectrometry, were used to elucidate the structure of the hexasaccharide moiety linked by the novel O-glycosidic linkage to tyrosine. The combined evidence suggests the following structure: beta-D-Galf-(1-->3)-alpha-D Galp- (1-->2)-alpha-L-Rhap-(1-->3)-alpha-D-Manp-(1--3)-alpha-L- Rhap-(1-->3)-beta D-Glcp-(1-->4)-L-Tyr. PMID- 8444788 TI - Regulation of pyocin genes in Pseudomonas aeruginosa by positive (prtN) and negative (prtR) regulatory genes. AB - Most strains of Pseudomonas aeruginosa produce various types of bacteriocins (pyocins), namely, R-, F-, and S-type pyocins. The production of all types of pyocins was shown to be regulated by positive (prtN) and negative (prtR) regulatory genes. The prtN gene activates the expression of various pyocin genes, probably by the interaction of its product with the DNA sequences conserved in the 5' noncoding regions of the pyocin genes. The prtR gene represses the expression of the prtN gene, and its product, predicted from the nucleotide sequence, has a structure characteristic of phage repressors and seems to be inactivated by the RecA protein activated by DNA damage. A model for the regulation of the pyocin genes is proposed. PMID- 8444789 TI - Evolution of bacteriophage T7 in a growing plaque. AB - The emergence of mutants during the 10(9)-fold amplification of a bacteriophage was spatially resolved in a growing plaque. When wild-type phage T7 was grown on an Escherichia coli host which expressed an essential early enzyme of the phage infection cycle, the T7 RNA polymerase, mutant phage relying on this enzyme appeared in 10(8) phage replications and outgrew the wild type. Spatial resolution of the selection process was achieved by analyzing stab samples taken along a plaque radius. Different mutants were selected at different rates along different radii of the plaque, based on host range and restriction patterns of the isolates. The mutants deleted up to 11% of their genomes, including the gene for their own RNA polymerase. They gained an advantage over the wild type by replicating more efficiently, as determined by one-step growth cultures. PMID- 8444790 TI - Involvement of an activation protein in the methanol:2-mercaptoethanesulfonic acid methyltransferase reaction in Methanosarcina barkeri. AB - Methanol:5-hydroxybenzimidazolylcobamide methyltransferase (MT1) is the first of two enzymes required for transfer of the methyl group of methanol to 2 mercaptoethanesulfonic acid in Methanosarcina barkeri. MT1 binds the methyl group of methanol to its corrinoid prosthetic group only when the central cobalt atom of the corrinoid is present in the highly reduced Co(I) state. However, upon manipulation of MT1 and even during catalysis, the enzyme becomes inactivated as the result of Co(I) oxidation. Reactivation requires H2, hydrogenase, and ATP. Ferredoxin stimulated the apparent reaction rate of methyl group transfer. Here we report that one more protein fraction was found essential for the overall reaction and, more specifically, for formation of the methylated MT1 intermediate. The more of the protein that was present, the shorter the delay of the start of methyl group transfer. The maximum velocity of methyl transfer was not substantially affected by these varying amounts of protein. This demonstrated that the protein was involved in the activation of MT1. Therefore, it was called methyltransferase activation protein. PMID- 8444791 TI - Unicellular, aerobic nitrogen-fixing cyanobacteria of the genus Cyanothece. AB - Two marine, unicellular aerobic nitrogen-fixing cyanobacteria, Cyanothece strain BH63 and Cyanothece strain BH68, were isolated from the intertidal sands of the Texas Gulf coast in enrichment conditions designed to favor rapid growth. By cell morphology, ultrastructure, a GC content of 40%, and aerobic nitrogen fixation ability, these strains were assigned to the genus Cyanothece. These strains can use molecular nitrogen as the sole nitrogen source and are capable of photoheterotrophic growth in the presence of 3-(3,4-dichlorophenyl)-1,1 dimethylurea and glycerol. The strains demonstrated a doubling time of 10 to 14 h in the presence of nitrate and 16 to 20 h under nitrogen-fixing conditions. Rapid growth of nitrogen-fixing cultures can be obtained in continuous light even when the cultures are continuously shaken or bubbled with air. Under 12-h alternating light and dark cycles, the aerobic nitrogenase activity was confined to the dark phase. The typical rates of aerobic nitrogenase activity in Cyanothece strains BH63 and BH68 were 1,140 and 1,097 nmol of C2H2 reduced per mg (dry weight) per h, respectively, and nitrogenase activity was stimulated twofold by light. Ultrastructural observations revealed that numerous inclusion granules formed between the photosynthetic membranes in cells grown under nitrogen-fixing conditions. These Cyanothece strains posses many characteristics that make them particularly attractive for a detailed analysis of the interaction of nitrogen fixation and photosynthesis in an aerobic diazotroph. PMID- 8444792 TI - Cloning and DNA sequence of the gene coding for Clostridium thermocellum cellulase Ss (CelS), a major cellulosome component. AB - Clostridium thermocellum ATCC 27405 produces an extracellular cellulase system capable of hydrolyzing crystalline cellulose. The enzyme system involves a multicomponent protein aggregate (the cellulosome) with a total molecular weight in the millions, impeding mechanistic studies. However, two major components of the aggregate, SS (M(r) = 82,000) and SL (M(r) = 250,000), which act synergistically to hydrolyze crystalline cellulose, have been identified (J. H. D. Wu, W. H. Orme-Johnson, and A. L. Demain, Biochemistry 27:1703-1709, 1988). To further study this synergism, we cloned and sequenced the gene (celS) coding for the SS (CelS) protein by using a degenerate, inosine-containing oligonucleotide probe whose sequence was derived from the N-terminal amino acid sequence of the CelS protein. The open reading frame of celS consisted of 2,241 bp encoding 741 amino acid residues. It encoded the N-terminal amino acid sequence and two internal peptide sequences determined for the native CelS protein. A putative ribosome binding site was identified at the 5' end of the gene. A putative signal peptide of 27 amino acid residues was adjacent to the N terminus of the CelS protein. The predicted molecular weight of the secreted protein was 80,670. The celS gene contained a conserved reiterated sequence encoding 24 amino acid residues found in proteins encoded by many other clostridial cel or xyn genes. A palindromic structure was found downstream from the open reading frame. The celS gene is unique among the known cel genes of C. thermocellum. However, it is highly homologous to the partial open reading frame found in C. cellulolyticum and in Caldocellum saccharolyticum, indicating that these genes belong to a new family of cel genes. PMID- 8444793 TI - A mutation in algN permits trans activation of alginate production by algT in Pseudomonas species. AB - Conversion of the mucoid phenotype, which results from the production of the exopolysaccharide alginate, is a feature typical of Pseudomonas aeruginosa strains causing chronic pulmonary infections in patients with cystic fibrosis. In this study, we further characterized a recombinant plasmid, called pJF15, that contains DNA from the 65- to 70-min region of the chromosome of mucoid P. aeruginosa FRD1 and has loci involved in alginate conversion. Plasmid pJF15 complements algT mutations in trans and confers the mucoid phenotype in cis following gene replacement. However, the phenotype of nonmucoid P. aeruginosa carrying pJF15 is unchanged. Here we report the identification of a locus immediately downstream of algT, called algN, that may be a negative regulator that blocks algT from activating alginate production. Inactivation of algN by transposon Tn501 insertion allowed algT to stimulate alginate production in trans. The DNA sequence of this region identified an open reading frame that predicts an algN gene product of 33 kDa, but no homology was found to other proteins in a sequence data base. Clones of algT in which algN was deleted caused the activation of alginate biosynthesis in transconjugants of several P. aeruginosa strains. DNA containing algT was shown to hybridize to the genomes of several Pseudomonas species, including P. putida, P. stutzeri, and P. fluorescens. Transconjugants of these species carrying algT DNA (with a deletion of algN) from pJF15 showed a mucoid phenotype and increased production of uronic acid-containing polymers that resembled alginate. PMID- 8444794 TI - Molecular analysis of the phoH gene, belonging to the phosphate regulon in Escherichia coli. AB - By making operon fusions with lambda placMu53, we identified, cloned, and analyzed the phoH gene belonging to the phosphate (pho) regulon. We mapped the phoH gene at 23.6 min in the Escherichia coli genomic library (Y. Kohara, K. Akiyama, and K. Isono, Cell 50:495-508, 1987). Its nucleotide sequence revealed an open reading frame of 354 amino acids which contains sequences for nucleotide binding motifs. From comparison of the DNA sequences, phoH was found to be identical to psiH, which had been identified as a phosphate starvation-inducible gene (W.W. Metcalf, P.M. Steed, and B.L. Wanner, J. Bacteriol. 172:3191-3200, 1990). The PhoH protein was overproduced by the T7 promoter system, identified as a protein of about 39 kDa, and purified. The amino-terminal amino acid sequence of the PhoH protein agreed with the one deduced from the DNA sequence. We demonstrated that PhoH has an ATP-binding activity by a photoaffinity labeling experiment. Two transcriptional initiation sites (P1 and P2) were identified by S1 nuclease mapping. The upstream P1 promoter contains a pho box, the conserved sequence shared by the pho regulon genes. The region containing the pho box was bound by PhoB protein, the transcriptional activator of the pho regulon, as revealed by footprinting. Regulation of phoH expression in vivo was studied by constructing plasmids containing transcriptional fusions of the phoH promoters with a promoterless gene for chloramphenicol acetyltransferase. Transcription from the P1 promoter required the phoB function and was induced by phosphate limitation, while transcription from the P2 promoter was independent of phoB and constitutive under tested conditions. PMID- 8444795 TI - Lipoic acid metabolism in Escherichia coli: sequencing and functional characterization of the lipA and lipB genes. AB - Two genes, lipA and lipB, involved in lipoic acid biosynthesis or metabolism were characterized by DNA sequence analysis. The translational initiation site of the lipA gene was established, and the lipB gene product was identified as a 25-kDa protein. Overproduction of LipA resulted in the formation of inclusion bodies, from which the protein was readily purified. Cells grown under strictly anaerobic conditions required the lipA and lipB gene products for the synthesis of a functional glycine cleavage system. Mutants carrying a null mutation in the lipB gene retained a partial ability to synthesize lipoic acid and produced low levels of pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase activities. The lipA gene product failed to convert protein-bound octanoic acid moieties to lipoic acid moieties in vivo; however, the growth of both lipA and lipB mutants was supported by either 6-thiooctanoic acid or 8-thiooctanoic acid in place of lipoic acid. These data suggest that LipA is required for the insertion of the first sulfur into the octanoic acid backbone. LipB functions downstream of LipA, but its role in lipoic acid metabolism remains unclear. PMID- 8444796 TI - The Escherichia coli FtsH protein is a prokaryotic member of a protein family of putative ATPases involved in membrane functions, cell cycle control, and gene expression. AB - The ftsH gene is essential for cell viability in Escherichia coli. We cloned and sequenced the wild-type ftsH gene and the temperature-sensitive ftsH1(Ts) gene. It was suggested that FtsH protein was an integral membrane protein of 70.7 kDa (644 amino acid residues) with a putative ATP-binding domain. The ftsH1(Ts) gene was found to have two base substitutions within the coding sequence corresponding to the amino acid substitutions Glu-463 by Lys and Pro-587 by Ala. Homology search revealed that an approximately 200-amino-acid domain, including the putative ATP-binding sequence, is highly homologous (35 to 48% identical) to the domain found in members of a novel, eukaryotic family of putative ATPases, e.g., Sec18p, Pas1p, CDC48p, and TBP-1, which function in protein transport pathways, peroxisome assembly, cell division cycle, and gene expression, respectively. Possible implications of these observations are discussed. PMID- 8444797 TI - Topology and subcellular localization of FtsH protein in Escherichia coli. AB - FtsH protein in Escherichia coli is an essential protein of 70.7 kDa (644 amino acid residues) with a putative ATP-binding sequence. Western blots (immunoblots) of proteins from fractionated cell extracts and immunoelectron microscopy of the FtsH-overproducing strain showed exclusive localization of the FtsH protein in the cytoplasmic membrane. Most of the FtsH-specific labeling with gold particles was observed in the cytoplasmic membrane and the adjacent cytoplasm; much less was observed in the outer membrane and in the bulk cytoplasm. Genetic analysis by TnphoA insertions into ftsH revealed that the 25- to 95-amino-acid region, which is flanked by two hydrophobic stretchs, protrudes into the periplasmic space. From these results, we concluded that FtsH protein is an integral cytoplasmic membrane protein spanning the membrane twice and that it has a large cytoplasmic carboxy-terminal part with a putative ATP-binding domain. The average number of FtsH molecules per cell was estimated to be approximately 400. PMID- 8444798 TI - Posttranslational regulation of nitrogenase in Rhodobacter capsulatus: existence of two independent regulatory effects of ammonium. AB - In the photosynthetic bacterium Rhodobacter capsulatus, nitrogenase activity is regulated by ADP-ribosylation of component II in response to the addition of ammonium to cultures or to the removal of light. The ammonium stimulus results in a fast and almost complete inhibition of the in vivo acetylene reduction activity, termed switch-off, which is reversed after the ammonium is exhausted. In the present study of the response of cells to ammonium, ADP-ribosylation of component II occurred but could not account for the extent and timing of the inhibition of activity. The presence of an additional response was confirmed with strains expressing mutant component II proteins; although these proteins are not a substrate for ADP-ribosylation, the strains continued to exhibit a switch-off response to ammonium. This second regulatory response of nitrogenase to ammonium was found to be synchronous with ADP-ribosylation and was responsible for the bulk of the observed effects on nitrogenase activity. In comparison, ADP ribosylation in R. capsulatus was found to be relatively slow and incomplete but responded independently to both known stimuli, darkness and ammonium. Based on the in vitro nitrogenase activity of both the wild type and strains whose component II proteins cannot be ADP-ribosylated, it seems likely that the second response blocks either the ATP or the electron supply to nitrogenase. PMID- 8444799 TI - Prevention of DNA damage in spores and in vitro by small, acid-soluble proteins from Bacillus species. AB - The DNA in dormant spores of Bacillus species is saturated with a group of nonspecific DNA-binding proteins, termed alpha/beta-type small, acid-soluble spore proteins (SASP). These proteins alter DNA structure in vivo and in vitro, providing spore resistance to UV light. In addition, heat treatments (e.g., 85 degrees C for 30 min) which give little killing of wild-type spores of B. subtilis kill > 99% of spores which lack most alpha/beta-type SASP (termed alpha beta - spores). Similar large differences in survival of wild-type and alpha - beta - spores were found at 90, 80, 65, 22, and 10 degrees C. After heat treatment (85 degrees C for 30 min) or prolonged storage (22 degrees C for 6 months) that gave > 99% killing of alpha - beta - spores, 10 to 20% of the survivors contained auxotrophic or asporogenous mutations. However, alpha - beta spores heated for 30 min at 85 degrees C released no more dipicolinic acid than similarly heated wild-type spores (< 20% of the total dipicolinic acid) and triggered germination normally. In contrast, after a heat treatment (93 degrees C for 30 min) that gave > or = 99% killing of wild-type spores, < 1% of the survivors had acquired new obvious mutations, > 85% of the spore's dipicolinic acid had been released, and < 1% of the surviving spores could initiate spore germination. Analysis of DNA extracted from heated (85 degrees C, 30 min) and unheated wild-type spores and unheated alpha - beta - spores revealed very few single-strand breaks (< 1 per 20 kb) in the DNA. In contrast, the DNA from heated alpha- beta- spores had more than 10 single-strand breaks per 20 kb. These data suggest that binding of alpha/beta-type SASP to spore DNA in vivo greatly reduces DNA damage caused by heating, increasing spore heat resistance and long-term survival. While the precise nature of the initial DNA damage after heating of alpha- beta- spores that results in the single-strand breaks is not clear, a likely possibility is DNA depurination. A role for alpha/beta-type SASP in protecting DNA against depurination (and thus promoting spore survival) was further suggested by the demonstration that these proteins reduce the rate of DNA depurination in vitro at least 20-fold. PMID- 8444800 TI - The Escherichia coli K-12 F plasmid gene traX is required for acetylation of F pilin. AB - The Escherichia coli F plasmid gene required for amino-terminal acetylation of F pilin subunits was identified. Using Western blots (immunoblots), we assayed the reaction of monoclonal antibodies with F-pilin polypeptides in inner membrane preparations from various F mutant strains. It was known that JEL92 recognizes an internal pilin epitope and JEL93 recognizes the acetylated amino-terminal sequence (L.S. Frost, J.S. Lee, D.G. Scraba, and W. Paranchych, J. Bacteriol. 168:192-198, 1986). As expected, neither antibody reacted with inner membranes from F- cells or Flac derivatives that do not synthesize pilin. Mutations that affected the individual activities of F tra genes traA, -B, -C, -D, -E, -F, -G, H, -I, -J, -K, -L, -M, -N, -P, -R, -U, -V and -W or trb genes trbA, -B, -C, -D, E, -G, -H, and -I did not prevent JEL92 or JEL93 recognition of membrane pilin. However, Hfr deletion mutants that lacked the most-distal transfer region genes did not express pilin that reacted with JEL93. Nevertheless, all strains that retained traA and traQ did express JEL92-reactive pilin polypeptides. Analysis of strains expressing cloned tra segments showed that traA and traQ suffice for synthesis of JEL92-reactive pilin, but synthesis of JEL93-reactive pilin is additionally dependent on traX. We concluded that the traX product is required for acetylation of F pilin. Interestingly, our data also showed that TraA+ TraQ+ cells synthesize two forms of pilin which migrate at approximately 7 and 8 kDa. In TraX+ cells, both become acetylated and react with JEL93. Preparations of wild type F-pilus filaments contain both types of subunits. PMID- 8444801 TI - Characterization of the genes of the 2,3-butanediol operons from Klebsiella terrigena and Enterobacter aerogenes. AB - The genes involved in the 2,3-butanediol pathway coding for alpha-acetolactate decarboxylase, alpha-acetolactate synthase (alpha-ALS), and acetoin (diacetyl) reductase were isolated from Klebsiella terrigena and shown to be located in one operon. This operon was also shown to exist in Enterobacter aerogenes. The budA gene, coding for alpha-acetolactate decarboxylase, gives in both organisms a protein of 259 amino acids. The amino acid similarity between these proteins is 87%. The K. terrigena genes budB and budC, coding for alpha-ALS and acetoin reductase, respectively, were sequenced. The 559-amino-acid-long alpha-ALS enzyme shows similarities to the large subunits of the Escherichia coli anabolic alpha ALS enzymes encoded by the genes ilvB, ilvG, and ilvI. The K. terrigena alpha-ALS is also shown to complement an anabolic alpha-ALS-deficient E. coli strain for valine synthesis. The 243-amino-acid-long acetoin reductase has the consensus amino acid sequence for the insect-type alcohol dehydrogenase/ribitol dehydrogenase family and has extensive similarities with the N-terminal and internal regions of three known dehydrogenases and one oxidoreductase. PMID- 8444802 TI - Gene transfer in Cryptococcus neoformans by use of biolistic delivery of DNA. AB - A transformation scheme for Cryptococcus neoformans to yield high-frequency, integrative events was developed. Adenine auxotrophs from a clinical isolate of C. neoformans serotype A were complemented by the cryptococcal phosphoribosylaminoimidazole carboxylase gene (ade2) with a biolistic DNA delivery system. Comparison of two DNA delivery systems (electroporation versus a biolistic system) showed notable differences. The biolistic system did not require linear vectors and transformed each auxotrophic strain at similar frequencies. Examination of randomly selected transformants by biolistics showed that 15 to 40% were stable, depending on the recipient auxotroph, with integrative events identified in all stable transformants by DNA analysis. Although the ade2 cDNA copy transformed at a low frequency, DNA analysis found homologous recombination in each of these transformants. DNA analysis of stable transformants receiving genomic ade2 revealed ectopic integration in a majority of cases, but approximately a quarter of the transformants showed homologous recombination with vector integration or gene replacement. This system has the potential for targeted gene disruption, and its efficiency will also allow for screening of DNA libraries within C. neoformans. Further molecular strategies to study the pathobiology of this pathogenic yeast are now possible with this transformation system. PMID- 8444803 TI - Molecular analysis of the 3,6-dideoxyhexose pathway genes of Yersinia pseudotuberculosis serogroup IIA. AB - Salmonella enterica and Yersinia pseudotuberculosis are the only examples in nature known to use a variety of 3,6-dideoxyhexose derivatives as O antigen constituents. To allow a comparison of the responsible biosynthetic genes of the two organisms, we have sequenced a section of the Y. pseudotuberculosis serogroup IIA rfb region that contained the genes for the abequose biosynthetic pathway. Comparison of the identified genes with the rfb region of S. enterica LT2 showed that the two dideoxyhexose pathway gene clusters are related. The arrangement of the genes was largely conserved, and the G + C compositions of the two DNA regions were strikingly similar; however, the degree of conservation of nucleotide and protein sequences suggested that the two gene clusters have been evolving independently for considerable time. Hybridization experiments showed that the dideoxyhexose pathway genes are widespread throughout the various serogroups of Y. pseudotuberculosis. PMID- 8444804 TI - Cloning, nucleotide sequence, and regulation of the Bacillus subtilis nadB gene and a nifS-like gene, both of which are essential for NAD biosynthesis. AB - A number of Bacillus subtilis genes involved in NAD biosynthesis have been cloned and sequenced. One of the genes encodes a polypeptide homologous to Escherichia coli L-aspartate oxidase, and its mutation resulted in a nicotinic acid (Nic) dependent phenotype; this gene was termed nadB. A second open reading frame (orf2) was found downstream of nadB, and an insertional plasmid separating orf2 and nadB also gave a Nic-dependent phenotype. This result suggests that orf2 may also be involved in NAD biosynthesis and that nadB and orf2 are in the same operon. Upstream of nadB was a third gene, transcribed in the opposite direction to that of nadB-orf2. The amino acid sequence derived from the third gene was quite similar to those derived from nifS genes of various nitrogen-fixing bacteria; therefore, the third gene was termed nifS. As with nadB and orf2, mutations in nifS also resulted in a Nic-dependent phenotype. The promoter regions of nadB and nifS overlapped each other and both contained -10 and -35 sequences which resemble those of E sigma A-type promoters. Transcription from both the nifS and nadB promoters, as well as expression of a nadB-lacZ fusion, was repressed by Nic. However, nadB transcription and nadB-lacZ expression were decreased, at most, only slightly by a deletion in nifS. The possible role of the nifS gene product in NAD biosynthesis is discussed. PMID- 8444805 TI - SPL1-1, a Saccharomyces cerevisiae mutation affecting tRNA splicing. AB - A genetic approach was used to isolate and characterize Saccharomyces cerevisiae genes affecting tRNA processing. Three mutants were isolated which were able to process and utilize splicing-deficient transcripts from inactivated Schizosaccharomyces pombe suppressor tRNA genes. Extragenic recovery of suppressibility was verified by the suppression of nonsense mutations in LEU2, HIS4, and ADE1. One mutant, SPL1-1, was chosen for detailed analysis on the basis of its increased synthesis of mature suppressor tRNA over wild-type cell levels as determined by Northern (RNA) analysis. This mutant exhibited strong suppression exclusively with the defective tRNA gene used in the mutant selection. Genetic analysis revealed that a single, dominant, haplo-lethal mutation was responsible for the suppression phenotype. The mutation mapped on chromosome III to an essential 1.5-kb open reading frame (L. S. Symington and T. D. Petes, Mol. Cell. Biol. 8:595-604, 1988), recently named NFS1 (S. G. Oliver et al., Nature [London] 357:38-46, 1992), located adjacent (centromere proximal) to LEU2. PMID- 8444806 TI - A physiological role for cyanate-induced carbonic anhydrase in Escherichia coli. AB - Cyanate induces expression of the cyn operon in Escherichia coli. The cyn operon includes the gene cynS, encoding cyanase, which catalyzes the reaction of cyanate with bicarbonate to give ammonia and carbon dioxide. A carbonic anhydrase activity was recently found to be encoded by the cynT gene, the first gene of the cyn operon; it was proposed that carbonic anhydrase prevents depletion of bicarbonate during cyanate decomposition due to loss of CO2 by diffusion out of the cell (M. B. Guilloton, J. J. Korte, A. F. Lamblin, J. A. Fuchs, and P. M. Anderson, J. Biol. Chem. 267:3731-3734, 1992). The function of the product of the third gene of this operon, cynX, is unknown. In the study reported here, the physiological roles of cynT and cynX were investigated by construction of chromosomal mutants in which each of the three genes was rendered inactive. The delta cynT chromosomal mutant expressed an active cyanase but no active carbonic anhydrase. In contrast to the wild-type strain, the growth of the delta cynT strain was inhibited by cyanate, and the mutant strain was unable to degrade cyanate and therefore could not use cyanate as the sole nitrogen source when grown at a partial CO2 pressures (pCO2) of 0.03% (air). At a high pCO2 (3%), however, the delta cynT strain behaved like the wild-type strain; it was significantly less sensitive to the toxic effects of cyanate and could degrade cyanate and use cyanate as the sole nitrogen source for growth. These results are consistent with the proposed function for carbonic anhydrase. The chromosomal mutant carrying cynS::kan expressed induced carbonic anhydrase activity but no active cyanase. The cynS::kan mutant was found to be much less sensitive to cyanate than the delta cynT mutant at a low pCO2, indicating that bicarbonate depletion due to the reaction of bicarbonate with cyanate catalyzed by cyanase is more deleterious to growth than direct inhibition by cyanate. Mutants carrying a nonfunctional cynX gene (cynX::kan and delta cynT cynX::kan) did not differ from the parental strains with respect to cyanate sensitivity, presence of carbonic anhydrase and cyanase, or degradation of cyanate by whole cells; the physiological role of the cynX product remains unknown. PMID- 8444807 TI - The periplasmic dipeptide permease system transports 5-aminolevulinic acid in Escherichia coli. AB - In a genetic screen designed to generate Escherichia coli strains completely devoid of the heme precursor 5-aminolevulinic acid (ALA), we isolated a class of mutants which were defective for exogenous ALA uptake. The mutations, designated alu (ALA uptake), mapped to the 80-min region of the E. coli chromosome. They were complemented by a recombinant plasmid containing the dpp operon, which encodes a dipeptide permease transport system. Alu mutants displayed a severe reduction in ALA import, as did a strain with a chromosomal insertion in the first gene of the dpp operon. A recognized substrate of Dpp transport, prolyl glycine, effectively competed with ALA for uptake. E. coli strains defective in ALA biosynthesis (hemA or hemL) require exogenous ALA to achieve wild-type growth but show limited aerobic and anaerobic growth in the absence of ALA. The presence of an alu or dpp mutation in hemA or hemL strains abolishes growth in the absence of ALA and requires increased levels of ALA for normal growth. We conclude that the alu mutations are within the dpp operon and that the dipeptide transport system mediates uptake of the important metabolite ALA. PMID- 8444808 TI - Two independently regulated cytochromes P-450 in a Rhodococcus rhodochrous strain that degrades 2-ethoxyphenol and 4-methoxybenzoate. AB - A red-pigmented coryneform bacterium, identified as Rhodococcus rhodochrous strain 116, that grew on 2-ethoxyphenol and 4-methoxybenzoate as sole carbon and energy sources was isolated. Phylogenetic analysis based on the 16S rDNA sequences indicates that the strain clusters more closely to other rhodococci than to other gram-positive organisms with a high G + C content. Each of the abovementioned growth substrates was shown to induce a distinct cytochrome P-450: cytochrome P-450RR1 was induced by 2-ethoxyphenol, and cytochrome P-450RR2 was induced by 4-methoxybenzoate. A type I difference spectrum typical of substrate binding was induced in cytochrome P-450RR1 by both 2-ethoxyphenol (KS = 4.2 +/- 0.3 microM) and 2-methoxyphenol (KS = 2.0 +/- 0.1 microM), but not 4 methoxybenzoate or 4-ethoxybenzoate. Similarly, a type I difference spectrum was induced in cytochrome P-450RR2 by both 4-methoxybenzoate (KS = 2.1 +/- 0.1 microM) and 4-ethoxybenzoate (KS = 1.6 +/- 0.1 microM), but not 2-methoxyphenol or 2-ethoxyphenol. A purified polyclonal antiserum prepared against cytochrome P 450RR1 did not cross-react with cytochrome P-450RR2, indicating that the proteins are immunologically distinct. The cytochromes appear to catalyze the O dealkylation of their respective substrates. The respective products of the O dealkylation are further metabolized via ortho cleavage enzymes, whose expression is also regulated by the respective aromatic ethers. PMID- 8444809 TI - Derepression of LamB protein facilitates outer membrane permeation of carbohydrates into Escherichia coli under conditions of nutrient stress. AB - The level of LamB protein in the outer membrane of Escherichia coli was derepressed in the absence of a known inducer (maltodextrins) under carbohydrate limiting conditions in chemostats. LamB protein contributed to the ability of the bacteria to remove sugar from glucose-limited chemostats, and well-characterized lamB mutants with reduced stability constants for glucose were less growth competitive under glucose limitation than those with wild-type affinity. In turn, wild-type bacteria were less growth competitive than lamB mutants with enhanced sugar affinity. In contrast to an earlier report, we found that LamB- bacteria were less able to compete in carbohydrate-limited chemostats (with glucose, lactose, arabinose, or glycerol as the carbon and energy sources) when mixed with LamB+ bacteria. The transport Km for [14C]glucose was affected by the presence or affinity of LamB, but only in chemostat-grown bacteria, with their elevated LamB levels. The pattern of expression of LamB and the advantage it confers for growth on low concentrations of carbohydrates are consistent with a wider role in sugar permeation than simply maltosaccharide transport, and hence the well-known maltoporin activity of LamB is but one facet of its role as the general glycoporin of E. coli. A corollary of these findings is that OmpF/OmpC porins, present at high levels in carbon-limited bacteria, do not provide sufficient permeability to sugars or even glycerol to support high growth rates at low concentrations. Hence, the sugar-binding site of LamB protein is an important contributor to the permeability of the outer membrane to carbohydrates in habitats with low extracellular nutrient concentrations. PMID- 8444810 TI - Sulfolobus acidocaldarius synthesizes UMP via a standard de novo pathway: results of biochemical-genetic study. AB - A genetic approach was used to establish the route of UMP biosynthesis in Sulfolobus acidocaldarius, a member of the hyperthermophilic division (the Crenarchaeota) of the Archaea domain. Pyrimidine auxotrophs of S. acidocaldarius DG6 were isolated by direct selection and by brute-force methods. Enzymatic assay of extracts from wild-type S. acidocaldarius, from pyrimidine auxotrophs, and from phenotypic revertants demonstrated that S. acidocaldarius synthesizes UMP via orotate in six enzymatic steps corresponding to the de novo pathway of other organisms. The results also show that a single carbamoyl phosphate synthetase supplies both the pyrimidine and arginine pathways of this organism. To gain similar insight into pyrimidine salvage pathway(s), prototrophic mutants resistant to toxic pyrimidine analogs were also isolated and characterized. The results suggest that a single class of mutants which had acquired elevated resistance to four different 5-fluoropyrimidines had been isolated. These fluoropyrimidine-resistant mutants appear to have a regulatory defect leading to overproduction of one or more endogenous pyrimidine compounds. PMID- 8444811 TI - Analysis of 7-substituted sialic acid in some enterobacterial lipopolysaccharides. AB - Sialic acid-containing lipopolysaccharides (LPS) were isolated from six bacterial strains of the family Enterobacteriaceae. Sialic acid was released from permethylated LPS by methanolysis, and partially O-methylated N-acetyl-N-methyl neuraminic acid methyl ester methyl glycosides were analyzed by gas-liquid chromatography-electron ionization mass spectrometry. It was proved that all LPS contain N-acetylneuraminic acid (NeuAc). The occurrence of 7-substituted NeuAc in Escherichia coli serotypes O24 and O56 and in Citrobacter freundii O37 LPS was documented. The LPS preparations also contained terminal NeuAc. LPS of E. coli O104 had exclusively 4-substituted sialic acid. The remaining LPS studied, namely, from Salmonella toucra O48 and Hafnia alvei 2, had 4-linked and terminally localized NeuAc residues. PMID- 8444813 TI - The rfaS gene, which is involved in production of a rough form of lipopolysaccharide core in Escherichia coli K-12, is not present in the rfa cluster of Salmonella typhimurium LT2. AB - Partial sequencing of the rfa cluster of Salmonella typhimurium LT2 indicated a region of 336 bp between rfaP and rfaB in the site occupied by the rfaS gene in Escherichia coli K-12. This region does not contain a functional rfaS gene, although DNA analysis suggests that the region may have contained an ancestral gene. This conclusion that S. typhimurium LT2 lacks rfaS is supported by its lipopolysaccharide (LPS) gel phenotype, since LT2 does not make the lipooligosaccharide band characteristic of LPS from smooth strains of E. coli K 12. PMID- 8444812 TI - Cloning, characterization, and functional expression in Escherichia coli of chaperonin (groESL) genes from the phototrophic sulfur bacterium Chromatium vinosum. AB - A recombinant lambda phage which was able to propagate in groE mutants of Escherichia coli was isolated from a Chromatium vinosum genomic DNA library. A 4 kbp SalI DNA fragment, isolated from this phage and subcloned in plasmid vectors, carried the C. vinosum genes that allowed lambda growth in these mutants. Sequencing of this fragment indicated the presence of two open reading frames encoding polypeptides of 97 and 544 amino acids, respectively, which showed high similarity to the molecular chaperones GroES and GroEL, respectively, from several eubacteria and eukaryotic organelles. Expression of the cloned C. vinosum groESL genes in E. coli was greatly enhanced when the cells were transferred to growth temperatures that induce the heat shock response in this host. Coexpression in E. coli of C. vinosum groESL genes and the cloned ribulose bisphosphate carboxylase/oxygenase genes from different phototrophic bacteria resulted in an enhanced assembly of the latter enzymes. These results indicate that the cloned DNA fragment encodes C. vinosum chaperonins, which serve in the assembly process of oligomeric proteins. Phylogenic analysis indicates a close relationship between C. vinosum chaperonins and their homologs present in pathogenic species of the gamma subdivision of the eubacterial division Proteobacteria. PMID- 8444814 TI - Construction and analysis of F plasmid traR, trbJ, and trbH mutants. AB - F plasmid derivatives carrying kan insertion mutations in the transfer region genes traR, trbJ, and trbH were constructed. Standard tests indicated that these loci are not essential for F pilus production or F transfer among Escherichia coli K-12 hosts. Among the traR and trbH mutants tested, the orientation of the kan cassette had no effect on the mutant phenotype. In each case, there was no significant effect on the appearance of F pili, the transfer frequency, or the plating efficiency of F-pilus-specific phages. The trbJ insertion carrying a kan gene oriented in the direction opposite to tra transcription had very little effect on phage sensitivity but markedly reduced the plasmid transfer efficiency. However, the kan insertion mutation at the same site, in the tra orientation, did not seem to affect either property. Analysis of clones carrying trbJ sequences regulated by a phage T7 promoter showed that trbJ expresses an approximately 11 kDa protein product. The TrbJ protein was not expressed from clones carrying a kan insertion or stop codon linker insertion in the trbJ sequence. However, it was expressed from clones that did not include sequences at the beginning of the 113-codon open reading frame in this region. Our data indicated that translation of trbJ must be initiated at the more distal GUG codon in this frame. This would result in expression of a 93-amino-acid polypeptide. PMID- 8444815 TI - Peptidoglycan tripeptide content and cross-linking are altered in Enterobacter cloacae induced to produce AmpC beta-lactamase by glycine and D-amino acids. AB - Induction of AmpC beta-lactamase in Enterobacter cloacae ATCC 13047 by D methionine, glycine, or D-tryptophan was accompanied by alterations in peptidoglycan composition and structure; in the case of D-methionine, it was also accompanied by morphologic changes. A decrease in peptidoglycan tripeptides was seen. With glycine, there was an increase in the proportion of diaminopimelic diaminopimelic cross-links. The possible implications of these changes for beta lactamase induction are discussed. PMID- 8444816 TI - Escherichia coli SecB, SecA, and SecY proteins are required for expression and membrane insertion of the bacteriocin release protein, a small lipoprotein. AB - The SecB, SecA, and SecY dependency of a small outer membrane lipoprotein in Escherichia coli, the bacteriocin release protein (BRP), was studied. The detrimental effect of BRP expression on the culture turbidity (quasi-lysis) was strongly reduced in the sec mutants. Immunoblotting and radioactive labeling experiments showed that the expression, membrane insertion, and processing of the BRP precursor are dependent on SecB, SecA, and SecY. Labeling experiments with hybrid BRP gene constructs revealed that the mature part of the BRP precursor and not its stable signal sequence is important for its SecB dependency. PMID- 8444817 TI - Location of the rpoN gene on the physical map of Escherichia coli. PMID- 8444818 TI - Physical map location of the rpoN gene of Escherichia coli. PMID- 8444819 TI - Location of the gene coding for GTP cyclohydrolase I on the physical map of Escherichia coli. PMID- 8444820 TI - Thyroid dysfunction in refractory depression: implications for pathophysiology and treatment. AB - BACKGROUND: Many studies of thyroid augmentation in refractory depression are methodologically weak, have had mixed results, and often do not include biological measures of hormonal effects. In this paper, recent clinical and preclinical research on thyroid dysfunction in refractory depression is reviewed. METHOD: A search of MEDLINE for articles published from 1970 to the present was conducted, in addition to a search of the bibliographies of published papers in this area. The clinical studies chosen for review included those in which the patient population was identified as having refractory depression and where a specific measure of thyroid function was used, such as thyroid indices, thyroid releasing hormone stimulation, or basal metabolic rate. Animal studies of depression using the learned helplessness experimental paradigm were also reviewed and included if they examined the factors involved in antidepressant treatment response. RESULTS: Fifty-two percent of patients with refractory depression in six clinical studies evidenced subclinical hypothyroidism (range, 29%-100%), which can be contrasted with a prevalence of approximately 8% to 17% in unselected populations of depressed patients. Four studies investigating an animal model of refractory depression strongly implicate a pathophysiologic role for hypothyroidism, perhaps mediated by altered beta-adrenergic function. CONCLUSION: These findings indicate that hypothyroidism is significantly associated with refractory depression, suggesting that this characterizes one biological subtype of refractory depression. Failure to rigorously investigate the effects of thyroid augmentation, including measures of thyroid and beta adrenergic function, may partly explain the ambiguous results from many treatment studies, and future research should incorporate these measures in the study of refractory depression. PMID- 8444821 TI - A prospective clinical evaluation of an equation to predict daily lithium dose. AB - BACKGROUND: Conclusions about the usefulness of lithium dose-prediction equations are often based on retrospective evaluations, and the paucity of prospective tests is striking. METHOD: We prospectively evaluated the safety and accuracy of a lithium-dose prediction equation in a group of 29 psychiatric patients. Predicted doses were computed and rounded to the nearest multiple of 300 mg, and the respective doses of lithium carbonate were given either two or three times a day. On Day 4 or 5 following treatment initiation, morning blood samples were collected 8 to 12 hours after administration of the last dose. Patients were monitored carefully for signs of lithium toxicity. RESULTS: All 29 subjects achieved lithium concentrations between 0.5 and 1.3 mmol/L within 5 days of beginning treatment, and no participant showed any signs of lithium toxicity. CONCLUSION: The equation may be a safe, reasonable alternative to empiric dosing. PMID- 8444822 TI - Zinc deficiency and childhood-onset anorexia nervosa. AB - BACKGROUND: We studied the association of zinc deficiency and childhood-onset anorexia nervosa because the relationship is controversial. METHOD: Anorexia nervosa was diagnosed on the basis of determined food avoidance, weight loss, preoccupation with body weight and energy intake, distorted body image, fear of fatness, self-induced vomiting, excessive exercising, and laxative abuse. Twenty six such children, admitted to a specialized eating disorders program within a children's hospital, formed the basis of the study. Zinc status was determined by measuring fasting plasma zinc levels and 24-hour urinary zinc excretion using atomic absorption spectrophotometry. Nutritional status was determined by using weight-for-height ratios. A trial of zinc supplementation was attempted using a 12-week double-blind crossover design, with 6 weeks of placebo and 6 weeks of treatment with 50 mg daily of oral zinc sulphate. RESULTS: Zinc deficiency was found to be common, with a significant correlation between fasting plasma zinc levels and malnutrition (Pearson r = .586, p = .004). Introduction of a normal diet rapidly returned zinc levels and weight-for-height ratios to the normal range. Children entering the study with relatively normal zinc levels gained weight no faster than those with low plasma zinc levels. Of seven trials of zinc supplementation, only three were completed, as inadequate oral intake threatened the health of the remaining four. CONCLUSION: Low zinc levels are common in childhood-onset anorexia nervosa, appear to be secondary to self-starvation, and are rapidly reversible without zinc supplementation. PMID- 8444823 TI - High initial nortriptyline doses in the treatment of depression. AB - BACKGROUND: Guidelines for doses of nortriptyline are generally somewhat vague and usually recommend a fairly wide dose range. Additionally, the safety and utility of beginning treatment at higher initial doses have not been adequately investigated. METHOD: Nortriptyline treatment was initiated with a 75- to 125-mg dose depending on weight in 26 depressed inpatients in an open-label study. RESULTS: The mean Hamilton Rating Scale for Depression score decreased by 45% within 1 week (p < .001) and remained essentially unchanged at the end of Week 2. Orthostatic hypotension was the side effect of major concern since it is virtually the only significant cardiovascular effect in young healthy individuals treated with tricyclic antidepressant medication. Only 2 patients developed orthostasis, which required additional treatment with fludrocortisone, and no patients were dropped from the study due to side effects. None of the patients evidenced significant ECG changes. Twenty-one patients (81%) reached therapeutic drug levels on the initial dose regimen by the end of Week 1. CONCLUSION: Subjects tolerated high initial doses well and appeared to reach significant benefit within the first week. However, double-blind controlled studies are needed before any definitive conclusions can be drawn. PMID- 8444824 TI - Does clozapine cause neuroleptic malignant syndrome? PMID- 8444825 TI - Fluoxetine-induced sexual dysfunction. PMID- 8444826 TI - Vasoconstrictive effects and SSRIs. PMID- 8444827 TI - Prevalence of trichotillomania in a college freshman population. PMID- 8444828 TI - Catatonia associated with depression secondary to complex partial epilepsy. PMID- 8444829 TI - Depression with anxiety and atypical depression. AB - Some forms of anxiety and affective disorder, such as panic disorder and major depression, appear distinct, but frequently symptoms of depression and anxiety occur together. The comorbidity of anxiety and depression not only has implications for the differential diagnosis of the disorder but affects the severity and course of illness and its responsiveness to treatment. The results of studies of atypical depression suggest that this form of depressive illness responds better to monoamine oxidase inhibiting medications than to tricyclic antidepressant agents, and this preferential responsiveness may in fact define the boundaries of atypical depression. The serotonin selective reuptake inhibitor paroxetine seems to have a beneficial effect on symptoms of anxiety and agitation in depressed patients. Further clinical research is needed, however, to determine the best way to manage depression with anxiety and atypical depression. PMID- 8444830 TI - Review of the cardiovascular effects of heterocyclic antidepressants. AB - We review the effects of heterocyclic antidepressant compounds on the cardiovascular system. It has been shown that tricyclic antidepressants (TCAs) slow intraventricular conduction, and this can be seen on a standard ECG as the increased QRS, PR, and QTc intervals. This prolonged conduction is dangerous to patients in two conditions. In overdose, delayed conduction may lead to a complete heart block or ventricular reentry arrhythmias. Either of these complications, or a combination of both, may lead to death. When treated with TCAs at therapeutic plasma levels, depressed patients with preexisting conduction disease, particularly bundle-branch block, are at higher risk to develop symptomatic A-V block than depressed patients free of conduction disorders. Clinically, the effects of TCAs on conduction does not differ significantly within the family of drugs. Who gets complications is much more a function of severity of the patient's preexisting cardiac condition. The most common cardiovascular effect of TCAs is orthostatic hypotension. Postural hypotension is more dangerous in elderly patients because it may lead to falls that cause serious physical injuries. Severe orthostatic hypotension is more likely to develop in depressed patients with left ventricular impairment and/or in patients taking other drugs like diuretics or vasodilators. Nortriptyline has been shown to cause significantly less serious postural blood pressure drops, an important difference between this drug and other TCAs. Another cardiovascular effect of TCAs is that they reduce ventricular arrhythmias. They share this property with Type 1A antiarrhythmic compounds, and a variety of Type 1 antiarrhythmics have recently been shown to increase mortality in postmyocardial infarction patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444831 TI - Pharmacologic treatment of depression in the elderly. AB - Depressive illness is the most common emotional disorder in those of advanced age, occurring in approximately one seventh of those over 65 years old. Despite its high prevalence, depression in the elderly is more complicated to diagnose and treat than depression in younger adults. Successful pharmacotherapy for depression in the elderly requires careful consideration of the pharmacodynamics and pharmacokinetics of antidepressant medications of various classes to balance the therapeutic effects and side effect profiles of these agents. The heterocyclic antidepressants are effective in the elderly, but their use in this population may be limited by anticholinergic and/or cardiovascular side effects. The monoamine oxidase inhibitors also are effective, but compliance problems limit their usefulness in older persons. The serotonin selective reuptake inhibitors have been shown to be effective in the elderly, and their side effect profiles are generally milder than those of the older agents. Elderly patients receiving psychotropic drug therapy must be monitored carefully because treatment failure due to undermedication and drug toxicity due to overmedication may have more severe consequences in older than in younger adults. PMID- 8444832 TI - Management of recurrent depression. AB - Research completed over the past decade has established the chronic and recurrent nature of major depression. To date, treatment for the prevention of recurrence has promoted the use of "maintenance" doses of antidepressant medications that are lower than the effective for the acute phase of treatment. Long-term randomized, double-blind studies of tricyclic antidepressant (TCA) maintenance therapy have shown, however, that full-dose treatment strategy has a highly significant prophylactic effect in preventing a new episode of depression for up to 5 years. Monthly interpersonal psychotherapy has also been shown to have a modest but significant effect on survival. Although prophylaxis with full-dose TCAs can be well tolerated by patients when proper education and support are provided, newer antidepressant agents with milder side effect profiles are being studied for their efficacy in long-term management of depression. The results of 1-year studies of maintenance therapy with serotonin selective reuptake inhibiting agents suggest that these medications will play a major role in prophylaxis for recurrent depression. PMID- 8444833 TI - The difficult depressed patient in perspective. AB - Depression is a serious, chronic, and debilitating illness warranting speedy and effective intervention by psychiatrists and other physicians who see patients with depressive symptoms, whether or not severe enough to meet diagnostic criteria. Effective treatments are available for depressive symptoms, including pharmacotherapy with tricyclic antidepressants, monoamine oxidase inhibiting agents, or newer medications; psychotherapy (including cognitive therapy, behavioral approaches, and interpersonal therapy); and electroconvulsive therapy. Studies have shown, however, that patients' depressive disorders or symptomatology is often not treated or patients receive such low levels of treatment that episodes are prolonged and tend to recur. The implications are that depression is inadequately recognized and treated. Many factors undoubtedly contribute to the underrecognition of illness and generally inadequate treatment received by many patients with depression. Nevertheless, greater awareness and more effective treatment of depressive symptoms are needed to decrease depression morbidity and mortality. PMID- 8444834 TI - Conformational states of mutant M13 coat proteins are regulated by transmembrane residues. AB - Mutational and structural analysis of the 28 viable bacteriophage M13 mutants obtained by randomized mutagenesis of the effective transmembrane (TM) segment of the 50-residue major coat (gene VIII) protein (residues 21-39) demonstrated that M13 coat protein functionality, as reflected by phage viability, is incompatible with an increase in Gly + beta-branched residue content in its TM core. SDS polyacrylamide gel electrophoresis and circular dichroism spectroscopy performed in membrane environments on purified mutant coat proteins revealed that these proteins exist in a range of state(s), identified as helical monomers and dimers and polymeric (alpha-helical and/or beta-sheet) species, of which relative populations, and thermally induced conformational transitions, were dependent uniquely upon mutation type and locus. Mutations to relatively polar residues (e.g. G23D, Y24D, Y24H, A27E, I32T, and T36S) stabilized principally monomeric species, while mutants with decreased beta-branched content in the protein TM hydrophobic core (e.g. V29A, V30A, V31A, V31L, and V33A) displayed mainly dimeric species. Mutation of Ile37-->Thr within a "Sternberg-Gullick" consensus sequence of the coat protein TM segment led to a highly oligomerized/polymerized protein. The overall results suggest that TM residues in M13 coat protein are not universal components of a hydrophobic anchor segment per se, but are further selected (i) to impart conformational flexibility to the TM segment through helix destabilization and (ii) to retain the capacity to regulate protein-protein association and packing motifs within membranes. PMID- 8444835 TI - Comparison of GLUT4 and GLUT1 subcellular trafficking in basal and insulin stimulated 3T3-L1 cells. AB - The two glucose transporter isoforms GLUT4 and GLUT1 present in 3T3-L1 cells were labeled in the insulin-stimulated and basal states with the impermeant bis mannose photolabel, 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis-(D-mannos- 4-yloxy)-2-propylamine. The redistributions of these labeled transporters from the plasma membrane to the low density microsome membrane fraction were followed while cells were maintained at either insulin-stimulated or basal steady states. In both these steady states GLUT4 and GLUT1 were continuously recycled. Analysis of the time courses for tracer-tagged GLUT4 and GLUT1 redistribution showed that the endocytosis rate constants were only approximately 30% slower in the insulin stimulated (0.08 and 0.093 min-1) compared with the basal (0.116 and 0.121 min-1) state. In the insulin-stimulated state, the rate constants for GLUT4 and GLUT1 exocytosis (0.086 and 0.096 min-1) were similar to those of endocytosis. In contrast, the exocytosis rate constants of GLUT4 and GLUT1 in the basal state were 0.01 and 0.035 min-1. We therefore conclude that the main effect of insulin is to increase GLUT4 and GLUT1 exocytosis rate constants by approximately 9- and 3-fold, respectively, and that the unique feature of the GLUT4 isoform is the very slow rate of exocytosis in the basal state. PMID- 8444836 TI - A structural difference between filaments of phosphorylated and dephosphorylated Acanthamoeba myosin II revealed by electric birefringence. AB - The actin-activated Mg(2+)-ATPase activity of filamentous Acanthamoeba myosin II is regulated by the state of phosphorylation of three sites at the C terminus of each heavy chain. This phosphorylation at the tip of the tails of monomers in a bipolar filament abolishes the activity of sites some 90 nm distant in the globular heads. Previous studies with copolymeric filaments of phosphorylated and dephosphorylated monomers strongly indicated that the activity of each monomer in a filament is dependent on the level of phosphorylation of neighboring monomers in the filament. We report here electric birefringence measurements showing that, although the overall structures of phosphorylated and dephosphorylated filaments are very similar, large, Mg2+ concentration-dependent differences in internal motion and flexibility are observed. Filaments of dephosphorylated myosin II appear to be about 50-fold stiffer than filaments of phosphorylated myosin II at 4 mM Mg2+. These results are consistent with a model in which the stiffness of the putative hinge region within the rod-like tail of each monomer is determined by the phosphorylation state of the C-terminal tails of overlapping, neighboring monomers. The flexibility of the filaments appears to be directly related to their actin-activated Mg(2+)-ATPase activity. PMID- 8444837 TI - Cross-linked amino acids in the protein pairs L3-L19 and L23-L29 of Bacillus stearothermophilus ribosomes after treatment with diepoxybutane. AB - Treatment of native 50 S ribosomal subunits of Bacillus stearothermophilus with the homobifunctional cross-linking reagent diepoxybutane generated two cross linked protein pairs, L3-L19 and L23-L29, which were isolated and identified. The analysis of the cross-linking sites at the amino acid level in both protein pairs is presented. Using a combination of sequence analysis and mass spectrometry it could be demonstrated that His-28 in protein L3 and the N-terminal amino acids Met-1, His-2, and His-3 in protein L19 are involved in forming the cross-link L3 L19. Within the pair L23-L29 Met-1 in protein L23 and Lys-4 in protein L29 were identified as cross-linking sites employing a similar approach. Comparison of our data with results derived from other cross-linking experiments showed that in general the structural organization of the ribosomes in eubacteria (the Gram positive B. stearothermophilus and the Gram-negative Escherichia coli) has been conserved to quite an extent during evolution but that the fine structures differ slightly. By mass spectrometry the specificity of diepoxybutane and its cleaving mechanism using sodium periodate could be examined. In addition the complete amino acid sequence of protein L19 of B. stearothermophilus has been determined and revealed 58% identical amino acid residues to the homologous E. coli protein L19. PMID- 8444838 TI - The complete murine immunoglobulin class switch region of the alpha heavy chain gene-hierarchic repetitive structure and recombination breakpoints. AB - A 7255-base pair (bp) sequence, including the previously sequenced murine segments of I alpha, S alpha, and C alpha, has been completed. Homology matrix comparison revealed a switch repetitive region of 4.2 kilobases (kb) composed of 20-80-bp homology runs, including the previously assigned S alpha region. We distinguished several stretches of duplication, i.e. the central 0.8-kb repetitive region, with some 80-bp staggered consensus repeats containing 20-30 bp subsets, made up of the primordial pentamers CTG(A/G)G. All the break-points of the S alpha switch recombination, including those generated by the translocation of the c-myc protooncogene and those catalyzed by bacterial extracts, are located within the consensus sequence subsets of the 4.2-kb repetitive region. PMID- 8444839 TI - Alteration of coenzyme specificity of malate dehydrogenase from Thermus flavus by site-directed mutagenesis. AB - On the basis of the crystal structure of the NAD-dependent cytoplasmic malate dehydrogenase (MDH) and its alignment with NADP-dependent counterparts, the loop region between beta-strand B and alpha-helix C in the dinucleotide-binding fold was predicted as a principal determinant for the coenzyme specificity. Two mutants, EX7 and EX3, of NAD-dependent MDH from Thermus flavus were constructed. In the EX7 mutant, the seven loop amino acids in positions 41-47, Glu-Ile-Pro-Gln Ala-Met-Lys, were replaced by the corresponding loop residues in the NADP dependent MDH from chloroplasts, Gly-Ser-Glu-Arg-Ser-Phe-Gln. In the EX3 mutant, Glu-41, Ile-42, and Ala-45 were substituted with the corresponding 3 amino acids in the NADP-dependent chloroplast MDH. In both mutations the coenzyme specificity was altered from NAD to NADP. Especially, the EX7 mutation resulted in a more than 1000-fold improvement in overall catalytic efficiency with NADPH and a 600 fold decrease in the efficiency with NADH as cofactors. Consequently, EX7 mutant was 132 times more efficient with NADPH than NADH without a large decrease in turnover number. PMID- 8444840 TI - Movement of the retinylidene Schiff base counterion in rhodopsin by one helix turn reverses the pH dependence of the metarhodopsin I to metarhodopsin II transition. AB - The environment of the retinylidene Schiff base in bovine rhodopsin has been studied by movement of its carboxylic acid counterion from position 113 to position 117 by site-specific mutagenesis. Replacement of the counterion at position 113 by a neutral amino acid residue has been shown to produce a lowering of the Schiff base acidity constant (pKa) from > 8.5 to about 6. The aim of the present work was to change the position of the counterion without causing a significant effect on the Schiff base pKa. A triple replacement mutant (Glu113- >Ala/Ala117-->Glu/Glu122-->Gln) was designed to move the position of the counterion by one helix turn in the third putative transmembrane helix (helix C). The mutant bound 11-cis-retinal to form a chromophore with a visible absorbance maximum (lambda max) of 490 nm which was independent of pH in the range of about 5-8.5. Upon illumination under conditions in which rhodopsin was converted to the active metarhodopsin II (MII) photoproduct, the mutant was converted to a metarhodopsin I (MI)-like species (lambda max = 475 nm). Furthermore, the effect of pH on the photobleaching behavior of the mutant was the reverse of that reported for rhodopsin. In the mutant, acidic pH favored the formation of the MI like photoproduct, and basic pH favored the formation of an MII-like photoproduct (lambda max = 380 nm). The MII-like photoproduct of the mutant pigment was able to activate the guanine nucleotide-binding protein, transducin. We conclude that the Schiff base counterion in rhodopsin can be repositioned to form a pigment with an apparently unperturbed Schiff base pKa. Furthermore, a specific amino acid residue that acts as a Schiff base proton acceptor is not strictly required for photoconversion of rhodopsin to its active MII form. PMID- 8444841 TI - Preparation of affinity-fractionated, heparin-derived oligosaccharides and their effects on selected biological activities mediated by basic fibroblast growth factor. AB - Homogeneously sized, heparin-derived oligosaccharides were prepared from heparin following partial depolymerization with nitrous acid, reduction with sodium borohydride, and fractionation by gel permeation chromatography. The resulting pools of di-, tetra-, hexa-, octa-, and decasaccharides were sequentially applied to an affinity column of human recombinant basic fibroblast growth factor (bFGF) covalently attached to Sepharose 4B and further fractionated into subpools based on their elution from this column in response to gradients of sodium chloride. In general, pools of smaller heparin-derived oligosaccharides required relatively lower salt concentration for complete elution, and pools of larger oligosaccharides required higher salt concentration. The homogeneously sized pools and affinity-fractionated subpools of heparin-derived oligosaccharides were quantitatively assessed as inhibitors or enhancers of specific bFGF-mediated biological activities in five separate assay systems as follows: assay 1, to compete with human lymphoblastoid cells expressing syndecan (RO-12 UC cells) for binding to bFGF-coated wells (Ishihara, M., Tyrrell, D.J., Kiefer, M.C., Barr, P.J., and Swiedler, S.J. (1992) Anal. Biochem. 202, 310-315); assay 2, to inhibit 125I-bFGF binding to "low affinity sites" of adrenocortical endothelial (ACE) cells; assay 3, to inhibit bFGF-induced proliferation of ACE cells; assay 4, to support mitogenic activity of bFGF in a growth stimulation assay of chlorate treated ACE cells; and assay 5, to enhance the in vitro interaction between 125I bFGF and the recombinant extra-cellular domain of FGF high affinity receptor. The data derived from the five assay systems demonstrated that heparin-derived hexa- and octasaccharides inhibited the interaction between cell surface heparan sulfate proteoglycan and bFGF (assays 1 and 2) and bFGF-induced proliferation of ACE cells (assay 3) but were unable to enhance the binding of bFGF to its high affinity receptor in vitro (assay 5) or to support bFGF-induced mitogenesis in ACE cells (assay 4). These two activities required at least a decasaccharide with high affinity for bFGF. PMID- 8444842 TI - Structure and biological activities of a heparin-derived hexasaccharide with high affinity for basic fibroblast growth factor. AB - We demonstrated previously that heparin-derived hexasaccharides are the smallest fragments of the polysaccharide with comparable basic fibroblast growth factor (bFGF)-modulating activity in vitro (Ishihara, M., Tyrrell, D.J., Stauber, G.B., Brown, S., Cousens, L., and Stack, R.J. (1993) J. Biol. Chem. 268, 4675-4683. In this report, a specific hexasaccharide having high affinity for recombinant human bFGF was isolated and its structure deduced by analysis of its reduced disaccharide products after treatment with nitrous acid at pH 1.5, and by 1H NMR spectroscopy. The hexasaccharide has the structure [IdoA(2-OSO3)alpha 1 4GlcNSO3(6-OSO3)alpha 1-4]2IdoA(2-OSO3)alpha 1-4 AManR(6-OSO3). The hexasaccharide effectively inhibits the binding of syndecan-transfected RO-12 UC cells to bFGF-coated wells (Ishihara, M., Tyrrell, D.J., Kiefer, M.C., Barr, P.J., and Swiedler, S.J. (1992) Anal. Biochem. 202, 310-315), prevents the binding of 125I-bFGF to confluent monolayers of adrenocortical endothelial (ACE) cells, and inhibits the bFGF-dependent proliferation of ACE cells. Unlike the heparin from which it was derived, however, the hexasaccharide cannot promote the binding of 125I-bFGF to a recombinant high affinity bFGF receptor (flg) or restore the bFGF-dependent proliferative response to ACE cells grown in the presence of 5 mM sodium chlorate. Collectively, these data indicate that a hexasaccharide can be as effective as heparin as an antagonist of bFGF-mediated cell mitogenesis. PMID- 8444843 TI - Enhancement of the spermidine uptake system and lethal effects of spermidine overaccumulation in ornithine decarboxylase-overproducing L1210 cells under hyposmotic stress. AB - The D-R cell subline, an ornithine decarboxylase-overproducing variant of L1210 mouse leukemia cells, shows a growth advantage at low osmolality due to its high putrescine content. We tested the ability of spermidine to fulfill the role of putrescine under hyposmotic conditions. Although spermidine (1-30 microM) had no effect on growth under normosmotic conditions (325 mosm/kg), it was strongly inhibitory to D-R cell proliferation at 150 mosm/kg in a concentration-dependent manner. Hypotonic shock greatly increased the rate of spermidine uptake in D-R cells. The increased spermidine content enhanced total putrescine synthesis through a large induction of cytosolic spermidine/spermine N1-acetyltransferase activity but also promoted the excretion of most of the putrescine synthesized by the cells. Delaying the addition of spermidine until 24 h after hypotonic shock resulted in a much sharper decrease in D-R cell viability and strongly depressed polyamine contents. These lethal effects occurred between 8 and 24 h after spermidine addition and followed a dramatic increase in the rate and extent of spermidine accumulation which overrode the metabolic capacity of the N1 acetyltransferase/polyamine oxidase (PAO) pathway. Inhibition of PAO partly reversed the effect of spermidine on growth when the polyamine was added at the time of hypotonic shock, but not 24 h later. Similar experiments performed with alpha-methylspermidine, a metabolically resistant analog, which can completely fulfill cellular requirements for spermidine in normosmotic media, suggested that the lethal effect of a delayed spermidine addition is caused predominantly by excessive accumulation with a minor contribution resulting from stress due to polyamine oxidase activity. In contrast, in hypotonically shocked L1210 cells, spermidine stimulated cell proliferation (albeit less effectively than putrescine), there was no lethal effect of a delayed addition of alpha methylspermidine, and there was no time-dependent increase in the rate of alpha methylspermidine uptake. Thus, the spermidine transport system is strongly enhanced by hyposmotic shock in D-R cells, which can result in extensive cell death from overaccumulation of the polyamine and, to a lesser extent, from stress related to the PAO-catalyzed degradation of N1-acetylspermidine. The absence of these effects in parental L1210 cells indicates that the acquisition of an ornithine decarboxylase-overproducing phenotype also involves major modifications in the expression and/or regulation of polyamine transport. PMID- 8444844 TI - Demonstration of a novel type of ATP-diphosphohydrolase (EC 3.6.1.5) in the bovine lung. AB - A novel type of ATP-diphosphohydrolase (ATPDase) is demonstrated in bovine lung. The enzyme has an optimum pH of 7.5 and catalyzes the hydrolysis of the beta- and gamma-phosphate residues from diphospho- and triphosphonucleosides. It requires Ca2+ or Mg2+ and is insensitive to ouabain, an inhibitor of Na+/K(+)-ATPase, P1,P5-di(adenosine 5')-pentaphosphate, an inhibitor of adenylate kinase, and tetramisole, an inhibitor of alkaline phosphatase. In contrast, sodium azide (10 mM), a known inhibitor of ATPDases and mitochondrial ATPases, as well as mercuric chloride (10 microM) and gossypol (2,2'-bis[8-formyl-1,6,7-trihydroxy-5-isopropyl 3-methylnaphthalene]) (35 microM) are powerful inhibitors of this enzyme. The same inhibition profile is obtained with ATP or ADP as substrate, thereby supporting the concept of a common catalytic site for these substrates. This is further confirmed by enzyme localization after polyacrylamide gel electrophoresis under nondenaturing conditions and by kinetic properties, namely pH dependence profiles, heat inactivation, and 60Co irradiation-inactivation curves. The native molecular mass of the enzyme calculated from 60Co gamma-irradiation-inactivation curves is estimated at 70 +/- 3 kDa, whereas Km,app and Vmax,app of the ATPDase are evaluated at 7 +/- 2 microM and 1.1 +/- 0.3 mumol of Pi/min/mg protein, respectively. A comparison of the kinetic properties of this ATPDase with those of pig pancreas (Type I) and bovine aorta (Type II) lead us to believe that this enzyme is an hitherto undescribed type of ATPDase. By reference to the previously described ATPDase, we propose to identify this enzyme as ATPDase Type III (EC 3.6.1.5). PMID- 8444845 TI - Prothymosin alpha is phosphorylated in proliferating stimulated cells. AB - Prothymosin alpha is a widely distributed polypeptide whose function, though unknown, seems to be related to cell proliferation. In vitro, it is a substrate for casein kinase-2. In this work, extracts of mitogenically stimulated murine splenic lymphocytes labeled with [32P] orthophosphate were found to contain [32P]prothymosin alpha. Phosphorylation activity was highly dependent on mitogenic activation with concanavalin A plus interleukin-2. While cells remained viable, phosphorylation increased with stimulation time in the presence of [32P]orthophosphate. Structural analysis showed that prothymosin alpha was phosphorylated at Thr residues located among its first 14 amino acids, whereas its in vitro phosphorylation by casein kinase-2 affects both Ser and Thr residues in this fragment, apparently in similar proportions. Thus, casein kinase-2 seems not to be responsible for the phosphorylation of prothymosin alpha in vivo. Prothymosin alpha was also found to be phosphorylated in proliferating murine thymocytes and HeLa cells; the phosphorylation sites were the same as in splenic lymphocytes, but the rate of phosphorylation was about 5 times lower. In thymocytes and subconfluent HeLa cells, the [32P]prothymosin alpha concentrations of the cytosolic and nuclear fractions were similar; in splenic lymphocytes, [32P]prothymosin alpha was found mostly in cytosol. PMID- 8444846 TI - Insoluble complex formation of lipoprotein (a) with low density lipoprotein in the presence of calcium ions. AB - We investigated whether apolipoprotein B-containing lipoproteins could bind to the insoluble complexes of lipoprotein (a) (Lp(a)) induced by Ca2+. Lp(a), but not low density lipoprotein (LDL), very low density lipoprotein (VLDL), or high density lipoprotein3 (HDL3) formed insoluble complexes at physiologic Ca2+ concentrations. Desialylation of Lp(a) dramatically decreased the ability of Lp(a) to aggregate, suggesting that sialic acids on Lp(a) were responsible for forming Ca2+ cross-bridges. Since a reduction of only 30% of the sialic acids on Lp(a) inhibited Ca(2+)-induced complex formation, it appears that only a small percentage of sialic acids on Lp(a) is involved in Ca(2+)-induced cross-bridging of Lp(a) particles. To determine whether other lipoproteins would complex to Lp(a) in the insoluble complexes, we mixed Lp(a) with LDL, VLDL, or HDL3 in the presence of Ca2+. Although both LDL and VLDL bound to the Lp(a) in the insoluble complexes, HDL3 not only did not bind, but it also prevented Lp(a) from forming insoluble complexes. LDL bound to Lp(a) in the insoluble complexes in a concentration-dependent manner, eventually reaching saturation at a molar ratio of 5:4 (LDL to Lp(a)). The interaction between LDL and Lp(a) appeared to be ionic, since increases in the positive charge on LDL by desialylation increased this interaction, whereas decreases in positive charge on LDL reduced this interaction. At higher Ca2+ concentrations, the binding of acetyl LDL to Lp(a) in the insoluble complexes was greater than that of LDL. Since more Ca2+ was required for concentration-dependent saturation of acetyl LDL binding, it is likely that Ca2+ cross-bridging was responsible for this binding. Thus, LDL, especially its modified forms, could contribute to the formation of insoluble complex of Lp(a) with Ca2+ in atherosclerotic lesions and help explain its preferential accumulation there. PMID- 8444847 TI - Partial purification and properties of a glucosyltransferase that synthesizes Glc1Man9(GlcNAc)2-pyrophosphoryldolichol. AB - The glucosyltransferase that transfers the first glucose residue from dolichyl-P glucose to Man9-(GlcNAc)2-PP-dolichol has been solubilized from porcine aorta and purified 720-fold. The purification strategy involved ammonium sulfate precipitation followed by ion-exchange, gel filtration, and hydroxylapatite column chromatographies. Analysis of the products produced by enzyme fractions at different stages of purification indicate that three different glucosyltransferases are involved in the conversion of Man9(GlcNAc)2-PP-dolichol to Glc3Man9(GlcNAc)2PP-dolichol. the first glucosyltransferase appears to be specific for dolichyl-P-glucose as the donor substrate. Man9(GlcNAc)2-PP dolichol, Man7(GlcNAc)2-PP-dolichol, and Man5(GlcNAc)2-PP-dolichol (with two different oligosaccharide structures) were tested for their ability to accept glucose from dolichyl-P-glucose. Studies on the comparative rates of transfer of glucose to these different acceptor substrates demonstrated that Man9(GlcNAc)2-PP dolichol accepts glucose at a higher initial rate and to a greater extent than does Man7(GlcNAc)2-PP-dolichol and the biosynthetic Man5(GlcNAc)2-PP-dolichol. The other Man5(GlcNAc)2-PP-dolichol (i.e. Man alpha 1,6[Man alpha 1,3]-Man alpha 1,6[Man alpha 1,3]Man beta 1,4GlcNAc beta 1, GlcNAc) was not an acceptor, indicating that the Man alpha 1,2-Man alpha 1,2Man alpha 1,3Man arm is necessary. Man9(Glc-NAc)2 and Man9(GlcNAc)2-protein were not acceptors, indicating that both the lipid and the oligosaccharide portion of Man9(GlcNAc)2-PP-dolichol are required for enzyme activity. The partially purified enzyme has a pH optimum of 6.5 and exhibits a requirement for divalent metal ions. PMID- 8444848 TI - The baculovirus Autographa californica encodes a protein tyrosine phosphatase. AB - The genome of the baculovirus Autographa californica encodes a 19-kDa protein (BVP) containing an active site sequence motif ((I/V)HCXAGXXR(S/T)G) that characterizes a large family of protein tyrosine phosphatases (PTPs). The baculoviral protein was expressed in Escherichia coli and purified so that its enzymatic properties could be examined. We have demonstrated that recombinant BVP has intrinsic protein tyrosine phosphatase activity. Like VH1, a PTP encoded by vaccinia virus, BVP also dephosphorylates seryl or threonyl residues. However, the similarity of BVP to VH1 or the catalytic domains from PTPs of eukaryotic origin is restricted to a small region surrounding the active site motif. In contrast, the similarity of BVP to two putative PTPs encoded by the CDC14 gene of Saccharomyces cerevisiae and a gene of unknown function from Caenorhabditis elegans extends throughout its sequence. We postulate that BVP and its two homologs constitute a unique subfamily that may differ from other PTPs in having a specialized function, mode of regulation, or substrate preference. PMID- 8444849 TI - In vitro and in vivo characterization of a neutral boron-containing thrombin inhibitor. AB - Peptide boronic acid derivatives have proven to be very potent inhibitors of serine proteases with boroarginine derivatives being particularly potent thrombin inhibitors. The importance of the charged side chain of arginine has been investigated by synthesizing a derivative in which this side chain has been replaced by a neutral one. This boronic acid derivative, D-benzyloxycarbonyl (Z) Phe-Pro-methoxypropylglycine-pinanediol (MpgC10H16), inhibited thrombin by a competitive mechanism with an inhibition constant (Ki) of 8.9 nM. In comparison to boroarginine derivatives, Z-D-Phe-Pro-boroMpgC10H16 displayed higher selectivity for thrombin over trypsin (Ki = 1.1 microM) and plasmin (Ki = 15.7 microM). Prolongation of thrombin time and activated partial thromboplastin time were observed with micromolar concentrations of Z-D-Phe-Pro-boroMpgC10H16. In a thrombin-dependent in vitro aggregation assay with human platelets, Z-D-Phe-Pro boroMpgC10H16 inhibited aggregation with an IC50 of 85 nM. When tested in a thrombin-dependent platelet accumulation model in the rat, a bolus injection of (Z)-D-Phe-Pro-boroMpgC10H16 (0.3-3 mg/kg) inhibited platelet accumulation. Thus, the substitution of the charged guanidino group in the P1 side chain by the neutral methoxy group resulted in a potent and highly selective thrombin inhibitor with an interesting pharmacological profile with in vitro as well as in vivo models. PMID- 8444850 TI - Hydration and allosteric transitions in hemoglobin. AB - Sucrose and other neutral solutes reduce the oxygen affinity of human hemoglobin. This effect was attributed by Colombo et al. (Colombo, M.F., Rau, D.C., and Parsegian, V.A. (1992) Science 256, 655-659) to a stabilization of the deoxy-T quaternary state of hemoglobin A, via a reduction of the activity coefficient of water. This was correlated to crystallographic results which showed that a significant surface area at the alpha 1 beta 2 interface, which is exposed to the solvent in the oxy-R state, is buried in the deoxy-T state. We show that sucrose has no effect on the oxygen affinity of trout hemoglobin I, which is cooperative in oxygen binding but lacks heterotropic effects, and that in spite of the large buried surface exposed to solvent upon dissociation of human hemoglobin into alpha beta dimers, sucrose leads either to an increased dissociation of hemoglobin A-CO into dimers or to no effect at all (in the presence of inositol hexakisphosphate). These results may demand a reconsideration of the hypothesis extensively discussed by Colombo et al. PMID- 8444851 TI - Selective deamidation of ribonuclease A. Isolation and characterization of the resulting isoaspartyl and aspartyl derivatives. AB - Selective deamidation of proteins and peptides is a reaction of great interest, whether it has physiological significance as in protein aging, or occurs as a disturbing event in the preparation of natural or recombinant proteins. Deamidation of bovine pancreatic ribonuclease A, RNase A, a classical model protein, has been reported to occur only after denaturation of the protein, or under harsh conditions. In this paper convenient procedures are described for selective deamidation of Asn67 in native RNase A under mild conditions. Furthermore, for the first time, both products of deamidation were isolated: the aspartyl and the isoaspartyl containing protein derivatives. Replacement of Asn67 with either residue lowers the catalytic activity of the enzyme, on RNA and on model substrates, except when a dinucleotide with a purine on the 5' side is the substrate. In the latter case an intriguing increase in the specificity constant is observed. The Asp67 derivative was found to refold, after full denaturation and reduction, at the same rate as the fully amidated protein, whereas the iso Asp67 derivative refolded at half that rate. It is hypothesized that this effect is due to a delayed formation of disulfide 65-72 for the presence of the abnormal isopeptide bond between residues 67 and 68. PMID- 8444852 TI - Purification and characterization of Saccharomyces cerevisiae DNA damage responsive protein 48 (DDRP 48). AB - A yeast protein was purified from wild type Saccharomyces cerevisiae (S. cerevisiae) to near homogeneity using an ethanolamine affinity chromatography procedure. The N-terminal amino acid sequencing and the amino acid composition analyses identified this protein as the product of the second open reading frame of S. cerevisiae DNA Damage-responsive gene 48 (DDR48) (Treger, J.M., and McEntee, K. (1990) Mol. Cell. Biol. 10, 3174-3184) The first methionine residue encoded by the translation starting codon was not present in the mature protein which is designated as DDRP 48. DDRP 48 was found to be a negatively charged and highly hydrophilic glycoprotein. The glycosidase cleavage analyses suggested that DDRP 48 was mainly N-link-glycosylated. The apparent molecular mass of DDRP 48 was estimated to be approximately 65 kilodaltons. DDRP 48 was found able to hydrolyze ATP and GTP yielding PPi. The Km values for ATP and GTP are 0.29 mM and 0.58 mM, respectively. The Western blot analysis demonstrated that DDRP 48 was expressed to various concentrations in different S. cerevisiae strains. Increased DDRP 48 abundance was observed after yeast cells carrying the wild type RAD 52 gene were exposed to either ethylmethane sulfonate or heat shock treatments. After similar DNA-damaging treatments, however, no significant inductions of DDRP 48 were found in a rad 52 mutant strain. These observations are consistent with the predictions resulting from previous studies on transcriptional regulation of the DDR 48 gene (Maga, J.A., McClanahan, T.A., and McEntee, K. (1986) Mol. & Gen. Genet. 205, 276-284; McClanahan, T., and McEntee, K. (1986) Mol. Cell. Biol. 6, 90-96). PMID- 8444853 TI - Molecular analysis of the neutral trehalase gene from Saccharomyces cerevisiae. AB - Neutral trehalase (EC 3.2.1.28) is a trehalose hydrolyzing enzyme of the yeast Saccharomyces cerevisiae (App, H., and Holzer, H. (1989) J. Biol. Chem. 264, 17583-17588). The gene of neutral trehalase was cloned by complementation of a neutral trehalase-deficient yeast mutant which was obtained by ethylmethanesulfonate mutagenesis. Three mutants without detectable neutral trehalase activity were obtained and characterized by tetrad analysis and found to belong to the same complementation group. The mutants were transformed with a S. cerevisiae genomic library in YEp24. Two overlapping plasmids were isolated, containing the neutral trehalase gene NTH1 with an open reading frame of 2079 base pairs (bp), encoding a protein of 693 amino acids, corresponding to a molecular mass of 79,569 Da. Several putative TATA boxes were found in the 5' nontranslated region of the NTH1 gene. In positions -652 to -641 a possible binding sequence for the MIG1 protein, a multicopy inhibitor of the GAL1 promotor, which also binds to the promotor sequences of the SUC2 and the FBP1 gene, was found. The start codon of the neutral trehalase is located about 2500 bp upstream of the centromere 4 consensus sequence elements I, II, and III (Mann, C., and Davis, R. W. (1986) Mol. Cell. Biol. 6, 241-245). Vicinity to a centromere is known to have a depressing influence on the number of plasmid copies per cell. This probably explains why transformation with pNTH does not lead to overexpression of neutral trehalase. The four consensus sequences AATAAA contained in the centromeric elements and reconfirmed by our sequencing data might be polyadenylation signals for NTH1-mRNA transcription termination. Northern blot analysis yielded a single mRNA species of approximately 2.3 kilobase(s). The neutral trehalase protein has a putative cAMP-dependent phosphorylation consensus sequence RRGS from amino acid positions 22-25. Therefore, the previously described activation of neutral trehalase by cAMP dependent phosphorylation is probably due to phosphorylation of serine 25. Three potential N-glycosylation sites (Asn-X-Ser/Thr) occur in the open reading frame of the neutral trehalase gene. However, no evidence for glycosylation could be detected by Western blotting.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8444854 TI - Kinetic analysis of a mutant (His107-->Tyr) responsible for human carbonic anhydrase II deficiency syndrome. AB - The replacement His107-->Tyr is a cause of carbonic anhydrase II deficiency syndrome in humans (Venta, P. J., Welty, R. J., Johnson, T. M., Sly, W. S., and Tashian, R. E. (1991) Am. J. Hum. Genet. 49, 1082-1090). We have prepared this mutant of human carbonic anhydrase II by site-directed mutagenesis and expressed it in Escherichia coli. The mutant was too unstable to purify; however, we were able to stabilize and store it at 4 degrees C in cell lysates containing 1-4 mg/ml bovine serum albumin. The concentration of this mutant in the lysate was determined by titration with the tight-binding inhibitor ethoxzolamide. The stability in this preparation was sufficient to determine that this mutant of carbonic anhydrase II has kcat/Km and apparent pKa for the hydration of CO2 equivalent to that of wild-type HCA II. The maximum velocity of CO2 hydration, which is dependent on the rate of proton transfer between enzyme and solution, was 3-fold smaller than for HCA II suggesting that the proton transfer pathway in the mutant is slightly less efficient than in wild type. Preliminary conformational energy calculations show that the replacement of His107 with the larger residue Tyr results in considerable distortion of the cavity surrounding site 107 and in the loss of at least two hydrogen bonds. PMID- 8444855 TI - Structural studies on the bacterial lyase-resistant tetrasaccharides derived from the antithrombin III-binding site of porcine intestinal heparin. AB - Three discrete tetrasaccharide structures which are resistant to Flavobacterium heparinase and heparitinases I and II were isolated from porcine intestinal heparin after exhaustive digestion with a mixture of all the above enzymes, and the tri-, tetra-, and penta-sulfated structures were determined by negative ion mode fast atom bombardment mass spectrometry and 500-MHz 1H NMR analysis as delta 4,5GlcA beta 1-4GlcNAc (6-sulfate)alpha 1-4GlcA beta 1-4GlcN(N,3-disulfate), delta 4,5 GlcA beta 1-4GlcNAc(6-sulfate)alpha 1-4GlcA beta 1-4GlcN (N,3,6 trisulfate), and delta 4,5GlcA beta 1-4GlcN (N,6-disulfate)alpha 1-4GlcA beta 1 4GlcN(N,3,6-trisulfate). The three components share the 3-O-sulfated reducing GlcN and the 6-O-sulfated internal GlcN, indicating that they are structural variants derived from the nonreducing portion of the minimal pentasaccharide sequence required for binding to antithrombin III. Isolation of the pentasulfated component has never been reported. Their unexpected resistance to heparitinases I and II indicates that 3-O-sulfation of the reducing GlcN contributes to the resistant nature of these tetrasaccharides to the enzymes. The present study demonstrates that the nonreducing trisaccharide portion of the structural variants of the antithrombin III-binding pentasaccharide sequence can be isolated in tetrasaccharides resistant to heparinase/heparitinases I and II, while the rest of the repeating region is degraded into disaccharide units. The lyase treatment is applicable to evaluation of heparin/heparan sulfate preparations in terms of the presence or absence of the specific structure containing the 3-O sulfated GlcN representing biosynthetic precursors, intermediates or final products of the binding site. PMID- 8444856 TI - Structural properties of high density lipoprotein subclasses homogeneous in protein composition and size. AB - We isolated native high density lipoprotein (HDL) subclasses homogeneous in size and in their protein content with the objective of investigating the differences and similarities in their apolipoprotein AI (apoA-I) structures. Defined particles were isolated from ultracentrifugally prepared HDL by immunoaffinity and gel-filtration chromatography. The isolated 88-A LpAI, 106-A LpAI, 96-A LpAI/AII particles (LpAI, particles contain only apoA-I; LpAI/AII, particles contain apoA-I and apoA-II), together with a 93-A reconstituted HDL were analyzed for purity, composition, and content of apolipoprotein molecules per particle, and were examined by far and near circular dichroism and intrinsic fluorescence spectroscopic methods, as well as by reaction kinetics with lecithin:cholesterol acyltransferase. The spectroscopic analyses indicated that the secondary structures and three-dimensional arrangements of apoA-I in all these particles are remarkably similar: their tryptophan residues are located in similar nonpolar environments and become exposed to increasing concentrations of guanidine hydrochloride in comparable denaturation steps; the 60-65% alpha-helical structures in apoA-I are denatured in similar patterns with 0-5 M denaturant concentrations. However, increasing surface lipid contents and the presence of apoA-II stabilize apoA-I on the HDL particles. The reaction kinetics with lecithin:cholesterol acyltransferase are similar and slow for the isolated HDL particles, reflecting product inhibition, and/or an apoA-I conformation that is unfavorable for the activation of the lecithin:cholesterol acyltransferase reaction. PMID- 8444857 TI - Potentiation of plasminogen activation by an anti-urokinase monoclonal antibody due to ternary complex formation. A mechanistic model for receptor-mediated plasminogen activation. AB - We have observed that a murine IgG1 monoclonal antibody directed against human urokinase-type plasminogen activator (uPA) greatly potentiates pro-uPA-mediated plasminogen activation. This effect was dependent on the interaction between the immunoglobulin and the kringle domain of pro-uPA and could be competed efficiently by kringle-containing proteolytic fragments of uPA. In addition, the potentiation could also be competed by the lysine analog 6-aminohexanoic acid, an antagonist of plasminogen binding. This unexpected plasminogen binding dependence was found to be due to a carboxyl-terminal lysine residue on the immunoglobulin gamma chain, which by analogy with other proteins represents a potential binding site for plasminogen. Removal of this residue with carboxypeptidase B resulted in a complete abolition of the potentiation. It appears therefore that the potentiatory effect involves a novel mechanism with the antibody acting to provide a specific template for the assembly of a ternary complex involving pro uPA/uPA and plasminogen, enabling them to interact in a catalytically favorable manner. This interpretation was confirmed by studying the kinetics of plasminogen activation by the complex between active, two-chain uPA and the antibody, which resulted in an overall 50-fold increase in reaction efficiency (kcat/Km), primarily due to a reduction in Km from 20 to 0.1 microM. Pro-uPA activation by plasmin was also accelerated, although to a lesser extent. The potentiation due to complex formation also provides a mechanism for the initiation of this system, dependent only on the low intrinsic proteolytic activity of the zymogen forms. The effects observed here, mediated by ternary complex formation, simulate the effects we have previously observed on assembly of the uPA receptor-mediated cellular plasminogen activation system and may therefore represent a mechanistic model for both its activity and initiation. PMID- 8444858 TI - Transmembrane domain length affects charge-mediated retention and degradation of proteins within the endoplasmic reticulum. AB - Previous studies have shown that the presence of potentially charged amino acid residues within the transmembrane domains of type I integral membrane proteins can result in protein retention and, in some cases, degradation within the endoplasmic reticulum (ER). An apparent exception to this observation is the CD3 epsilon chain of the T-cell antigen receptor complex, which is relatively stable in spite of having a transmembrane aspartic acid residue. A chimeric protein (T epsilon T) made by replacing the transmembrane domain of the Tac antigen with that of CD3-epsilon was normally transported to the cell surface, indicating that the transmembrane domain of CD3-epsilon was essentially unable to confer the phenotype of ER retention and degradation to another protein. Progressive shortening of the T epsilon T transmembrane domain, however, resulted in increasing retention and degradation of the mutant proteins in the ER. Conversely, a mutant Tac protein containing a single aspartic acid residue in its transmembrane domain was found to be retained and degraded in the ER, but when the transmembrane domain was lengthened, ER retention and degradation of the protein were abrogated. The aspartic acid residue in the transmembrane domain of all of these mutant proteins could mediate assembly with another protein having an arginine residue in its transmembrane domain, independent of the length of the transmembrane sequence. These findings demonstrate that the length of the hydrophobic transmembrane sequence has a critical influence on the ability of potentially charged transmembrane residues to cause protein retention and degradation in the ER. PMID- 8444859 TI - Initiation of lambda DNA replication. The Escherichia coli small heat shock proteins, DnaJ and GrpE, increase DnaK's affinity for the lambda P protein. AB - It is known that the initiation of bacteriophage lambda replication requires the orderly assembly of the lambda O.lambda P.DnaB helicase protein preprimosomal complex at the ori lambda DNA site. The DnaK, DnaJ, and GrpE heat shock proteins act together to destabilize the lambda P.DnaB complex, thus freeing DnaB and allowing it to unwind lambda DNA near the ori lambda site. The first step of this disassembly reaction is the binding of DnaK to the lambda P protein. In this report, we examined the influence of the DnaJ and GrpE proteins on the stability of the lambda P.DnaK complex. We present evidence for the existence of the following protein-protein complexes: lambda P.DnaK, lambda P.DnaJ, DnaJ.DnaK, DnaK.GrpE, and lambda P.DnaK.GrpE. Our results suggest that the presence of GrpE alone destabilizes the lambda P.DnaK complex, whereas the presence of DnaJ alone stabilizes the lambda P.DnaK complex. Using immunoprecipitation, we show that in the presence of GrpE, DnaK exhibits a higher affinity for the lambda P.DnaJ complex than it does alone. Using cross-linking with glutaraldehyde, we show that oligomeric forms of DnaK exhibit a higher affinity for lambda P than monomeric DnaK. However, in the presence of GrpE, monomeric DnaK can efficiently bind lambda P protein. These findings help explain our previous results, namely that in the GrpE-dependent lambda DNA replication system, the DnaK protein requirement can be reduced up to 10-fold. PMID- 8444860 TI - Phenylalanine hydroxylase-stimulating protein/pterin-4 alpha-carbinolamine dehydratase from rat and human liver. Purification, characterization, and complete amino acid sequence. AB - Phenylalanine hydroxylase-stimulating protein, also known as pterin-4 alpha carbinolamine dehydratase (PHS/PCD), was purified from rat and, for the first time, from human liver. We obtained their complete protein primary sequence using a combination of liquid secondary ionization mass spectrometry/tandem quadrupole mass spectrometry, electrospray ionization mass spectrometry, and Edman microsequence analysis. The amino acid sequences of human and rat PHS/PCD were found to be identical. Surprisingly, the primary structure of PHS/PCD is also essentially identical to a protein of the cell nucleus, named dimerization cofactor of hepatocyte nuclear factor 1 alpha, recently reported to be involved in transcription (Mendel, D. M., Khavari, P. A., Conley, P. B., Graves, M. K., Hansen, L. P., Admon, A., and Crabtree, G. R. (1991) Science 254, 1762-1767). PMID- 8444861 TI - Functional expression of human cathepsin S in Saccharomyces cerevisiae. Purification and characterization of the recombinant enzyme. AB - A cDNA encoding the human lysosomal cysteine proteinase cathepsin S precursor has been expressed in yeast using the pVT100-U expression vector containing the alpha factor promoter. The procathepsin S gene was expressed either as a fusion protein with the pre-region or with the prepro-region of the yeast alpha-factor precursor gene. Following in vitro processing both constructs gave an identical active mature enzyme with a molecular weight of 24,000. After prolonged cultivation of the cells the recombinant protein is also found as an active proteinase in the culture supernatant. The precursor can be activated in vitro at pH 4.5 and 40 degrees C under reducing conditions. The in vitro activated enzyme has a 6-amino acid NH2-terminal extension when compared with the native bovine enzyme. The purified enzyme displays a bell-shaped pH activity profile with a pH optimum of 6.5 and pK values of 4.5 and 7.8. The isoelectric point of the recombinant human cathepsin S is between 8.3 and 8.6 and about 1.5 pH units higher than for the bovine enzyme. The kinetic data for several synthetic substrates and inhibitors reveal a preference for smaller amino acid residues in the binding subsites S2 and S3 of cathepsin S. Like the bovine enzyme, the recombinant human cathepsin S is characterized by a broader range of pH stability (pH 5-7.5) than cathepsins B and L. PMID- 8444862 TI - Gene-specific DNA repair in xeroderma pigmentosum complementation groups A, C, D, and F. Relation to cellular survival and clinical features. AB - We have examined the gene- and strand-specific DNA repair of UV-induced cyclobutane pyrimidine dimers in fibroblasts from normal individuals and from patients with the DNA repair-deficient disorder xeroderma pigmentosum (XP). Cells were studied from XP complementation groups A, C, D, and F. DNA repair was assessed in the essential, active gene, dihydrofolate reductase (DHFR), in the active c-myc protooncogene, and in the transcriptionally inactive delta-globin gene. In addition, repair was studied in the individual strands of the DHFR gene in normal and group C cells. In the two strains of group C cells, we find preferential DNA repair of the DHFR gene and a strand bias of the repair with more repair in the transcribed strand. This is in general accordance with previously published reports (Venema, J., van Hoffen, A., Natarajan, A.T., van Zeeland, A.A., and Mullenders, L.H.F. (1990) Nucleic Acids Res. 18, 443-448; Venema, J., van Hoffen, A., and Mullenders, L.H.F. (1991) Mol. Cell. Biol. 11, 4128-4134), but we now find that there is more repair in the nontranscribed strand and less in the transcribed strand than what has been observed previously. In XP group A and D strains, we find little or no gene-specific DNA repair. In cells from an individual in XP complementation group F, we find less repair of dimers in the active gene than what has been observed for the overall genome. We have also measured the colony-forming ability of the strains after treatment with UV and find that this measure of survival does not correlate with the level of gene-specific repair of dimers. Thus, XP group F represents a novel repair phenotype with little or no gene-specific repair of dimers, but with relatively high UV resistance. We also evaluate the XP patients' clinical features in relation to gene-specific repair of dimers. PMID- 8444863 TI - Identification of molybdopterin as the organic component of the tungsten cofactor in four enzymes from hyperthermophilic Archaea. AB - The hyperthermophilic Archaea represent some of the most ancient organisms on earth. A study of enzymatic cofactors in these organisms could provide basic information on the origins of related cofactors in man and other more recently evolved organisms. To this end, the nature of the tungsten cofactor in aldehyde ferredoxin oxidoreductases from Pyrococcus furiosus and ES-4 and in formaldehyde ferredoxin oxidoreductases from P. furiosus and Thermococcus litoralis has been investigated. All four proteins contain molybdopterin, previously characterized as the organic component of the molybdenum cofactor in a large number of molybdoenzymes. Molybdopterin was identified by conversion to the dicarboxamidomethyl derivative by alkylation of the vicinal sulfhydryl groups on the pterin side chain and by conversion to the oxidized fluorescent derivative, Form A. The pterin of the tungsten cofactor in the four enzymes was examined for the presence of appended GMP, CMP, AMP, or IMP previously observed in molybdenum cofactors of some molybdoenzymes. No evidence for the presence of a molybdopterin dinucleotide or other modified form of molybdopterin was obtained. These results further document the essential nature of molybdopterin for the function of molybdenum and tungsten enzymes in diverse life forms. PMID- 8444864 TI - Heparin-binding transforming growth factor alpha-Pseudomonas exotoxin A. A heparan sulfate-modulated recombinant toxin cytotoxic to cancer cells and proliferating smooth muscle cells. AB - TGF alpha-PE40, a recombinant toxin in which transforming growth factor alpha (TGF alpha) is fused to a mutant form of Pseudomonas exotoxin, is selectively cytotoxic to cells bearing epidermal growth factor (EGF) receptors. Heparin binding EGF-like growth factor is a potent mitogen for smooth muscle cells capable of binding to both the EGF receptor and to immobilized heparin (Higashiyama, S., Abraham, J., Miller, J., Fiddes, J., and Klagsbrun, M. (1991) Science 251, 936-938). To study the effect of the heparin-binding domain in a chimeric toxin targeted to the EGF receptor, we fused the DNA sequence corresponding to the putative NH2-terminal heparin-binding (HB) domain of HB-EGF to chimeric toxins composed of TGF alpha and two different recombinant forms of Pseudomonas exotoxin (PE). One of these is a truncated form of PE devoid of the binding domain (TGF alpha-PE38); another is a mutant form of full-length toxin containing inactivating mutations in the binding domain and an altered carboxyl terminus (TGF alpha-PE4EKDEL). The resulting chimeric toxins HB-TGF alpha-PE38 and HB-TGF alpha-PE4EKDEL were expressed in Escherichia coli as inclusion bodies, refolded, and purified by heparin affinity chromatography. Both of the toxins were eluted from heparin at 0.8 M NaCl, in contrast to their respective TGF alpha toxins which were eluted at 0.15 M. Binding studies on A431 cells showed that the HB-TGF alpha toxins bound to the EGF receptor with an affinity similar to that of the TGF alpha toxins. However, cell killing studies on a panel of malignant cell lines showed that cytotoxicity was strongly affected by the presence of the HB domain. Cell lines expressing high numbers of EGF receptors such as A431 and KB were less sensitive to toxins containing the HB domain. Cells with low number of EGF receptors had similar responses to both types of toxins (MCF-7 and LNCaP) or were more sensitive to the toxin with the added HB domain (HEP-G2). HB-TGF alpha PE4EKDEL was over 10-fold more cytotoxic against proliferating vascular smooth muscle cells (VSMC) than to quiescent VSMC. Moreover, HB-TGF alpha-PE4EKDEL was 6 fold more potent than TGF alpha-PE4EKDEL to proliferating VSMC. Competition studies with EGF and/or heparin showed that heparin blocks the cytotoxicity of HB TGF toxins and the inhibitory action of heparin is stronger in cells expressing lower number of EGF receptors.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8444865 TI - Characterization of the gene for ADP-ribosylation factor (ARF) 2, a developmentally regulated, selectively expressed member of the ARF family of approximately 20-kDa guanine nucleotide-binding proteins. AB - ADP-ribosylation factors (ARFs) are a family of approximately 20-kDa guanine nucleotide-binding proteins that stimulate the ADP-ribosyltransferase activities of cholera toxin in vitro and function in protein trafficking in vivo. The six cloned mammalian ARFs can be grouped into three classes based on size and sequence identity. ARF 2 is a class I ARF, whose approximately 2.6-kilobase mRNA exhibits species and tissue selective expression and is developmentally regulated in rat brain. Here we report the sequence, structure, and functional promoter region of the bovine ARF 2 gene, which was facilitated by constructing a composite cDNA. The ARF 2 cDNA, constructed from a partial cDNA clone and polymerase chain reaction-amplified fragments from reverse-transcribed poly(A)+ RNA, was approximately 2270 base pairs (bp) (minus the poly(A) tail). In the 3' untranslated region, there are two potential polyadenylation signals, ATTAAA and AATAAA, at positions 1064 and 2232, respectively, and two ATTTA motifs, believed to signal mRNA degradation, at positions 2115 and 2165. The ARF 2 gene, represented in three overlapping genomic clones, spans approximately 20 kilobase pairs with five exons and four introns. Consensus sequences for guanine nucleotide-binding and GTP hydrolysis are in separate exons, except for the NKXD sequence, which is divided by intron 4. There are multiple transcriptional initiation sites. Transient transfection of embryonic trachea cells with deletion constructs defined the functional promoter region to be within 400 bp upstream of the most 5' site of transcription initiation. This 400-bp region lacks a TATA like sequence but contains six inverted CCAAT boxes, four potential Sp1-binding sites, and a potential AP-2-binding site. Although the pattern of expression of ARF 2 is unique among the ARFs, the structures of the class I ARF genes are conserved among its members and across species. PMID- 8444866 TI - Kinetic and regulatory mechanisms for (Escherichia coli) homoserine dehydrogenase I. Equilibrium isotope exchange kinetics. AB - Isotope exchange kinetics at chemical equilibrium were used to probe the mechanisms of substrate binding and regulatory behavior of homoserine dehydrogenase-I from Escherichia coli. At pH 9.0, 37 degrees C, Keq = 100 (+/- 20) for the catalyzed reaction: L-aspartate-beta-semialdehyde + NADPH + H+ = L homoserine + NADP+. Saturation curves for the exchange reactions, [14C]L homoserine <--> L-aspartate-beta-semialdehyde and [3H]NADP+ <--> NADPH were observed as a function of different reactant-product pairs, varied in constant ratio at equilibrium. The NADP+ <--> NADPH exchange rate was inhibited upon variation of pairs involving L-aspartate-beta-semialdehyde and L-homoserine, consistent with preferred order random binding of cofactors before amino acids. Optimal rate constants, derived by simulations of equilibrium isotope exchange kinetics data with the ISOBI program, indicate faster dissociation of amino acids than cofactors from the central complexes but nearly equal rates for association of cofactors and amino acids to free enzyme. Rate limitation of net turnover in both directions is determined by dissociation of cofactor from the E-cofactor complex. The allosteric modifier, L-threonine, produces distinctive perturbations of the saturation curves for isotope exchange, which were analyzed systematically with the ISOBI program. The best fit to the data was obtained by L-threonine inhibiting catalysis between the central complexes without altering substrate association-dissociation rates. Simulations also showed that rate-limiting catalysis suppresses the kinetic inhibition effects that are characteristic of preferred order substrate binding, producing patterns typical for a (rapid equilibrium) random kinetic scheme. PMID- 8444867 TI - Comparison of the acyl chain specificities of human myristoyl-CoA synthetase and human myristoyl-CoA:protein N-myristoyltransferase. AB - Human myristoyl-CoA synthetase and myristoyl-CoA:protein N-myristoyltransferase (hNmt) have been partially purified from an erythroleukemia cell line. Their substrate specificities were examined using two in vitro assays of enzyme activity together with a panel of C7-C17 saturated fatty acids plus 72 myristic acid analogs containing oxygen, sulfur, ketocarbonyl, ester, amide, cis and trans double bonds, triple bonds, and para-substituted phenyl groups. There is an inverse relationship between the polarity and the activity of C14 fatty acid substrates of myristoyl-CoA synthetase. Surveys of tetradecenoic and tetradecynoic acids suggest that myristate is bound to the synthetase in a bent conformation with a principal bend occurring in the vicinity of C5-C6. The synthetase can tolerate a somewhat wider range of physical chemical properties in acyl chains than can the monomeric hNmt. However, like myristoyl-CoA synthetase, there is an inverse relationship between acyl chain polarity and the activities of hNmt's acyl-CoA substrates. Moreover, the acyl chain of myristoyl-CoA appears to be bound to hNmt in a bent conformation with bends located in the vicinity of C5 and C8. The acyl chain specificities of both enzymes make them well suited to utilize efficiently any cellular pools of 5Z-tetradecenoic and 5Z,8Z tetradecadienoic acids and their CoA derivatives. This feature may account for the recent observation that in some mammalian cell lineages, certain N-myristoyl proteins are heterogeneously acylated with these C14 fatty acids. Finally, the acyl-CoA binding sites of human and Saccharomyces cerevisiae Nmts appear to have been highly conserved. Given their overlapping yet distinct peptide substrate specificities, development of species-specific inhibitors of Nmts should probably focus on structural features recognized in the enzymes' peptide substrates rather than in the acyl chain of their acyl-CoA substrates. PMID- 8444868 TI - Radiation signaling mediated by Jun activation following dissociation from a cell type-specific repressor. AB - The promoter regions of several radiation-inducible genes contain AP-1 cis-acting regulatory elements that are dependent upon protein kinase C signaling. We analyzed nuclear protein from irradiated human tumor cell lines for binding to the AP-1 consensus sequence. The increase in nuclear protein binding following irradiation was specific for the AP-1 sequence and was reduced by antibodies to c Jun and c-Fos. The AP-1 DNA binding sequence was found to regulate transcription in irradiated cells and mutation of the AP-1 site within the c-jun promoter abolished transcriptional induction by radiation. The gene encoding the chimeric transcription factor Gal4-Jun5-253, which includes the DNA binding region of Gal4 and the transcriptional regulatory region of c-Jun, was cotransfected with the reporter plasmid with Gal4 binding sequences (G5B-CAT). Transfection of RIT-3 and HeLa cells revealed that the regulatory region of Jun was sufficient to activate transcription following irradiation. Conversely, Hep G2 cells, which do not contain the cell type-specific Jun repressor, were not responsive to radiation induced Jun activation. The c-Jun repressor was found to regulate Jun activation by experiments using the expression vector CMV-jun, which competes for Jun inhibitor and eliminates radiation-induction of Jun. We propose transcription factor dissociation from inhibitor proteins may participate in the initiation of cellular responses to ionizing radiation. PMID- 8444869 TI - Histone synthesis and turnover in alfalfa. Fast loss of highly acetylated replacement histone variant H3.2. AB - Histone synthesis in alfalfa tissue culture cells was studied by labeling with tritiated lysine, purification of histone proteins by reversed-phase high pressure liquid chromatography, and fluorography of acid/urea/Triton X-100 polyacrylamide gels. Minor histone variant H3.2 was synthesized twice as fast as major variant H3.1. The predicted difference in histone H3 variant turnover was examined during continued growth. More than 50% of newly synthesized histone H3.2 and 20% of new H3.1 were lost from chromatin over a period of 100 h. This produced a ratio between the stable remaining portions of each new histone H3 variant protein identical to that of the steady-state histone H3 variants. The labile portion of new histone H3.2 (half-life of 20 h) was rapidly lost specifically from transcriptionally active chromatin as judged by the acetylation level of nearly 1.5 acetylated lysines/histone molecule, a level 50% higher than the acetylation in histone H3.2 overall and three times that of histone H3.1. These results and the constitutive level of H3.2 gene expression identify histone H3.2 of alfalfa as a functional replacement histone variant. The extent of its preferential assembly into active chromatin nucleosomes and the rapid rate of its subsequent loss indicate significant dissolution of plant nucleosomes during gene transcription. PMID- 8444870 TI - Dynamic methylation of alfalfa histone H3. AB - Dynamic lysine methylation of histone H3 in alfalfa tissue culture cells was studied by labeling with tritiated methionine, purification of variants H3.1 and H3.2 by reversed-phase high pressure liquid chromatography and amino acid analysis. Mono- and dimethyl-L-lysine were the major labeled amino acids. Within 100 h of continued growth conversion from N epsilon-monomethyl-L-lysine (MML) to N epsilon-dimethyl-L-lysine (DML) and N epsilon-trimethyl-L-lysine (TML) was observed, consistent with steady-state histone methylation. During the same time 20% of the methylation label was lost from major variant H3.1 protein and more than 50% from the more highly labeled minor variant H3.2. A similar pattern of label incorporation and loss was observed during a study of histone synthesis and turnover. This conforms with the general observation in animal cells that lysine methylation is limited to newly synthesized histone. Increased methylation of the more highly acetylated forms of histone H3 protein indicates limited accessibility of chromatin for histone methylation. After loss of the labile fraction of newly synthesized H3 variants, stably methylated proteins with 30% of the label in MML, 40% in DML, and 25% in TML remain. Turnover of methyl modification groups independent of histone turnover was not detected. PMID- 8444871 TI - Reversible translocation of 5-lipoxygenase in mast cells upon IgE/antigen stimulation. AB - The 5-lipoxygenase catalyzes the first two steps in the metabolism of arachidonic acid to leukotrienes. It has been shown that the calcium influx into leukocytes following stimulation by A23187 activates the enzyme and causes its translocation to the membrane. Leukotrienes are formed, and then the enzyme seems to be irreversibly inactivated. In the present investigation we have compared the effect of receptor-mediated mast cell activation (IgE/antigen) and A23187 on 5 lipoxygenase activity and translocation to the membrane. In contrast to the ionophore, IgE/antigen, which initiated the formation of similar amounts of leukotrienes as A23187, caused minor inactivation of the enzyme. Immunoblot analysis demonstrated that after antigen the membrane association of the 5 lipoxygenase was reversible, while with A23187 the translocation continued during the time of observation (60 min). Addition of a calcium chelator after ionophore challenge, prevented further inactivation of the enzyme and reversed its membrane binding. The data suggest that the continuous influx of calcium with A23187 is responsible for the extensive inactivation of the 5-lipoxygenase. In contrast, during receptor-mediated stimulation the transient increase in intracellular calcium seems to conserve the enzyme activity. PMID- 8444872 TI - Exon skipping caused by DNA recombination that introduces a defective donor splice site into the human glycophorin A gene. AB - We report here the pre-mRNA splicing of the human glycophorin Mz (HGpMz) gene altered by a defective donor splice site introduced into the third intron via the mechanism of gene conversion. We found that the directional transfer from HGpB(delta) to HGpA(alpha) of a 145-base pair silent homologous segment had resulted in HGpMz as an alpha-beta-alpha hybrid gene with a G-T transversion in the consensus GT motif of the 5'-donor splice site. Transcript analysis showed the presence in the Mz reticulocytes of three major glycophorin cDNA species of which two occurred as the shortened and aberrantly spliced products of HGpMz pre mRNA lacking the sequences encoded by one and two exons, respectively. The skipping of exon III results in one HGpMz protein with 99 amino acids that bears the M and Sta blood group antigens, whereas the coincident skipping of both exon III and exon IV leads to the expression of a minor HGpMz protein with 86 amino acids. These results indicate that the translocated defective donor splice site not only causes uniform skipping of the upstream exon but also affects the processing of the downstream exon. Complementing our previous studies, the finding that the active and inactive splice sites can be transposed by DNA recombination and alternatively used to construct new glycophorin alleles reveals a novel mechanism for sequence diversification in human genes. PMID- 8444873 TI - The VPS16 gene product associates with a sedimentable protein complex and is essential for vacuolar protein sorting in yeast. AB - The Saccharomyces cerevisiae vacuolar protein sorting mutant, vps16, exhibits pleiotropic defects in vacuolar protein targeting and vacuole morphology. To understand the role of the VPS16 gene in vacuolar protein sorting and organelle assembly, a vps16 ts mutant was used to clone the wild-type gene. DNA sequence analysis identified a single open reading frame within a vps16 complementing DNA fragment, capable of encoding a protein of 92,000 Da. Hydrophobicity analysis indicates that the Vps16 protein (Vps16p) is hydrophilic and contains no obvious signal sequence or membrane spanning domains. Gene disruption experiments have shown that VPS16 is not essential. delta vps16 cells exhibit, 1) a severe defect in vacuolar protein sorting; 2) a ts growth defect; 3) a grossly abnormal vacuole morphology, no normal vacuole compartment(s) is present; and 4) a defect in alpha factor processing. A trpE-Vps16 fusion protein has been used to generate polyclonal antiserum. This antiserum detects an unglycosylated protein of 90,000 Da. Subcellular fractionation studies indicate that the vast majority of the VPS16 gene product is associated with a particulate cell fraction. This association is resistant to detergent and salt extractions, but Vps16p can be extracted with 6 M urea and alkali buffer. In addition, overexpression of Vps16p appears to saturate the association sites available in this sedimentable structure. These data indicate that Vps16p may be specifically associated with a large protein complex, or with a limited number of sites on cytoskeletal elements of the cell. PMID- 8444874 TI - A 5' splice junction mutation leading to exon deletion in an Ashkenazic Jewish family with phosphofructokinase deficiency (Tarui disease). AB - A deficiency of the muscle isoform of the enzyme, phosphofructokinase (PFK, EC 2.7.1.11), leads to an illness (glycogenosis, Type VII) characterized by myopathy and hemolysis. A patient with this disease and an affected sister were found to have a G to A substitution at the 5' donor site of intron 5 of the PFK-M gene. This mutation led to a splicing defect: a complete deletion of the preceding exon in the patient's mRNA. The patient, an affected sister, and related and unrelated family members, who were of Ashkenazic Jewish background, were screened for the mutation by denaturing gradient gel electrophoresis and by allele specific hybridization of genomic DNA. The affected sisters are homozygous for the mutation, and their children, who are unaffected, are heterozygous. The only previously characterized genetic defect in this disease, found in a Japanese patient, was a G to T mutation at the beginning of intron 15 with splicing to a cryptic site within exon 15 (1). Both mutations lead to inframe deletions, but of different parts of the protein. The differences between the two aberrant proteins may account for clinical differences between our patients and the Japanese patient. PMID- 8444875 TI - Novel phosphorylation sites of eukaryotic initiation factor-4F and evidence that phosphorylation stabilizes interactions of the p25 and p220 subunits. AB - Only serine phosphorylation of eukaryotic initiation factor-4E (eIF-4E) has been previously reported in intact cells. We found that treatment of HepG2 cells with okadaic acid resulted in as much as 20% of eukaryotic initiation factor (eIF)-4E phosphorylation occurring on threonine residues and that tryptic phosphopeptide maps showed several previously unrecognized phosphopeptides. Analysis of p220 from control and okadaic acid-treated cells demonstrated serine and threonine phosphorylation under both conditions. However, a unique pattern of phosphopeptides in okadaic acid-treated cells was observed. The most notable finding was that hyperphosphorylation of eIF-4E and p220 increased binding of p220 but not eIF-4E to the m7GTP cap structure. We suggest that phosphorylation of eIF-4E is more complicated than previously recognized and that hyperphosphorylation of eIF-4E and p220 recruits more p220 into the protein complex that associates with mRNA caps. A better understanding of these protein protein and protein-mRNA interactions may aid the design of anti-sense directed chemistries that disrupt such interactions for a specific target mRNA (Baker, B.F., Miraglia, L., and Hagedorn, C. H. (1992) J. Biol. Chem. 267, 11495-11499). PMID- 8444876 TI - A serum response element and a binding site for NF-Y mediate the serum response of the human thrombospondin 1 gene. AB - The expression of thrombospondin 1 (TSP 1), a member of the TSP gene family, is rapidly induced by growth factors. We tested the ability of human TSP 1 chloramphenicol acetyltransferase constructs to respond to serum in stably transfected NIH-3T3 cells. Two transcriptional elements in the TSP 1 promoter, a distal element at -1280 and a proximal element at -65, were required for the response of the human TSP 1 gene to serum. The distal element contains the 5' CC(A + T)6GG-3' consensus sequence characteristic of a serum-response element (SRE). Deletions or mutations in this element reduced the serum response of the TSP 1 gene by 80-90%. In gel-shift assays, the -1280 element and the c-fos SRE cross-competed, whereas their functional and binding mutants did not. The proximal element contains the sequence 5'-GGCCAATGGG-3', which closely resembles the consensus binding motif for the CCAAT-binding factor NF-Y (CBF, CP1, alpha CP1). Deletions or mutations in this element also reduced the serum response by 80-90%. Methylation interference analysis of the -65 region identified a pattern of contacts with nuclear factors resembling that for NF-Y, and an NF-Y-binding site and the proximal TSP 1 element cross-competed in gel-shift assays, whereas their binding mutants did not. Finally, an abbreviated TSP 1 promoter/5'-flank, containing the SRE- and NF-Y-binding sites, mediated a serum response that was close in magnitude to that of the parent promoter. We conclude that the serum response of the human TSP 1 gene requires the coordinated function of an SRE- and NF-Y-binding site. PMID- 8444878 TI - Genetic and biochemical analyses of yeast TATA-binding protein mutants. AB - We have taken a combined genetic and biochemical approach to study TATA-binding protein (TBP) structure-function relationships. Using site-directed mutagenesis coupled with a screen for conditional lethal growth, we have isolated a number of temperature-sensitive TBP alleles in the region of amino acid positions 188, 189, and 190. Conditional growth is not a result of increased TBP turnover as most of the mutant proteins are stable in vivo as evidenced by immunoblot detection of TBP steady-state levels. DNA binding assays reveal that mutations at position 188 do not affect DNA binding activity of these mutants, even at high temperatures. Utilizing whole cell extracts which contain mutant TBPs in in vitro transcription experiments, we confirm that TBP is required for transcription by all three nuclear polymerases. However, certain of our TBP mutants are only compromised for RNA polymerase II transcription. PMID- 8444877 TI - Molecular cloning and characterization of PKC theta, a novel member of the protein kinase C (PKC) gene family expressed predominantly in hematopoietic cells. AB - Members of the protein kinase C (PKC) family of serine/threonine kinases play a key role in regulating the differentiation and growth of diverse cell types and, to date, the cloning of seven mammalian PKC genes encoding eight distinct isoforms has been reported. Here we describe the molecular cloning and deduced primary structure of a cDNA encoding a novel PKC isoform, termed PKC theta, which was isolated in the course of attempts to identify PKC genes that are expressed selectively in hematopoietic cells. Degenerate oligonucleotide primers corresponding to conserved sequence motifs, which distinguish the PKC family from other protein kinases, were employed in polymerase chain reactions (PCR) to amplify partial core sequences of putative PKC genes from a human peripheral blood lymphocyte-derived cDNA library. DNA sequencing of selected clones revealed several PKC-related sequences, including one that, on the basis of sequence comparison with known PKC isoforms, represented a novel PKC isoform. The complete cDNA sequence was determined by anchored PCR cloning and sequencing the entire coding sequence, using cDNA derived from a human leukemic T cell line (Jurkat). Included within this approximately 2.7-kilobase pair cDNA is an open reading frame of 2,118 nucleotides encoding a putative 82-kDa protein. The deduced primary structure contains consensus sequences characteristic of protein kinase catalytic domains and, based on its amino acid sequence and domain structure, is a member of the PKC family. PKC theta displays the highest homology to PKC delta, lacks the Ca(2+)-binding C2 domain and, thus, belongs to the subfamily of Ca(2+) independent PKC enzymes which also includes the delta, epsilon, zeta, and eta isoforms. RNase protection assays and semiquantitative PCR analysis indicated that, although PKC theta transcripts are expressed ubiquitously, the highest levels are found in hematopoietic tissues and cell lines, including T cells and thymocytes. In contrast, the expression levels in the brain and testes are considerably lower, and no transcripts were detected in several human carcinoma cell lines. A rabbit antiserum raised against a unique (V3 domain) bacterially expressed PKC theta fragment immunoprecipitated specifically an 82-kDa protein from Jurkat cell lysates. Thus, PKC theta represents an additional member of the PKC family, and its predominant expression in hematopoietic cells suggests that it may play a role in signal transduction and growth regulatory pathways unique to these cells. PMID- 8444879 TI - Human T cell leukemia virus type I Tax and phorbol 12-myristate 13-acetate induce expression of the A20 zinc finger protein by distinct mechanisms involving nuclear factor kappa B. AB - A20 was originally identified as a primary tumor necrosis factor alpha (TNF) responsive gene, which encodes a 790-amino acid zinc finger protein. A20 is expressed in a wide variety of cell lines, including fibroblasts, in which A20 expression protects cells from TNF cytotoxicity. An analysis of A20 expression in lymphocytic and monocytic cells lines revealed that A20 protein expression correlates with lymphocyte activation and monocyte differentiation. A20 expression was also induced in Jurkat T cells expressing the human T cell leukemia virus type I Tax protein. Transient transfection studies demonstrated that stimulation of A20 transcription by TNF, phorbol 12-myristate 13-acetate (PMA), and Tax was mediated by two kappa B elements within the A20 promoter. Accordingly, DNA electrophoretic mobility shift assays confirmed inducible binding of nuclear factor kappa B (NF-kappa B) to a promoter fragment containing both A20 kappa B elements. Analysis of individual A20 kappa B sites revealed that both kappa B sites were required for TNF or PMA activation of the A20 promoter; however, Tax activation required only one kappa B site. Overexpression of NF kappa B subunits activated the wild type A20 promoter, but did not activate mutated forms containing single kappa B sites. Thus, Tax activation of A20 transcription occurs through a mechanism distinct from PMA and TNF, possibly due to differential activation of NF-kappa B complexes or transcriptional cofactors. PMID- 8444880 TI - The TyrR protein of Escherichia coli, analysis by limited proteolysis of domain structure and ligand-mediated conformational changes. AB - The TyrR protein of Escherichia coli K12 is a homodimer containing 513 amino acids/subunit. This protein is important in the transcriptional regulation of several genes whose protein products catalyze steps in aromatic amino acid biosynthesis or transport. Methods were developed for efficiently purifying the TyrR protein to apparent homogeneity. We analyzed the pattern of cleavage of the TyrR protein by trypsin, either in the absence of ligands or in the presence of saturating levels of L-tyrosine, ATP, or poly(dI-dC). At low (1:200 ratio by weight) trypsin levels, in the absence of ligands, two major digestion products accumulated. These were polypeptides of 22 and 31 kDa, shown to contain amino acid residues 1-190 and 191-467, respectively. The pattern of trypsin cleavage was unaffected by tyrosine. In the presence of ATP, an intermediate species of 53 kDa, probably containing amino acid residues 1-467, was observed. The kinetics of appearance of the 53-kDa species were consistent with a role for ATP in accelerating the hydrolysis of the R467-F468 peptide bond. The 53-kDa polypeptide underwent further tryptic hydrolysis to yield fragments of 22 and 31 kDa. When both tyrosine and ATP were present, the rate of formation of the 22- and 31-kDa fragments was more rapid than in the absence of these ligands. It appears that when both ligands are bound, the rates of hydrolysis of peptide bonds R190-Q191 and R467-F468 are both enhanced. Additional limited proteolysis experiments suggested that polypeptide segment 191-467 contains ATP binding site(s), and that the rate of cleavage of peptide bonds R190-Q191 and R467-F468 is altered when the TyrR protein interacts with poly(dI-dC), an analog of target DNA. Our results reveal the presence of two major structural domains within the TyrR protein. The first domain (amino acid residues 1-190) is extremely resistant to hydrolysis by trypsin. The second domain (residues 191-467), which is likely to contain ATP binding site(s), is homologous to several other transcriptional activators specific for promoters responsive to the sigma 54 form of RNA polymerase. The remainder of the TyrR protein (residues 468-513) contains the operator recognition elements, probably arranged in the form of a helix-turn-helix motif. This polypeptide segment was not detected as a discrete tryptic hydrolysis product. PMID- 8444881 TI - Expression in Escherichia coli of the cloned flavin-containing monooxygenase from pig liver. AB - The amino acid sequence of pig liver flavin-containing monooxygenase (PgLFMO) was determined by nucleotide analysis of cDNA clones isolated using synthetic oligonucleotide probes. Most of the clones isolated were missing the 5'-noncoding region and the first seven codons including the putative initiation codon ATG. A full-length cDNA clone, PgLFMO1, was obtained by extending the 5'-end sequence to include an ATG initiation codon and the codons corresponding to the 5'-end using the polymerase chain reaction. Restriction sites for EcoRI and SalI were incorporated at the 5'- and 3'-ends of the cDNA, respectively, by polymerase chain reaction to provide a full-length cDNA clone, pTrcPgLFMO1. Escherichia coli strain NM522 was transformed with pTrcPgLFMO1 and the PgLFMO was expressed under the control of the Trc promoter. Recombinant PgLFMO isolated from the bacterial lysates was purified to homogeneity and found to have N- and S-oxygenation kinetic properties similar to those of the native enzyme. Stereoselective S oxygenation of (+)- and (-)-4-bromophenyl-1,3-oxathiolane or 2-methyl-1,3 benzodithiole by the expressed PgLFMO showed some differences from that of the native enzyme, however. These data indicate that active PgLFMO was expressed in E. coli but that the enzyme action was distinct from the native enzyme. PMID- 8444882 TI - Thyroxine targets different pathways of internalization of type II iodothyronine 5'-deiodinase in astrocytes. AB - In the brain, thyroid hormone dynamically regulates levels of the short-lived plasma membrane protein, type II iodothyronine 5'-deiodinase. In cultured astrocytes, thyroxine modulates deiodinase levels by activating cytoskeletal plasma membrane interactions that increase the rate of inactivation of the enzyme. Here we characterized the effects of these thyroxine-dependent cytoskeletal interactions upon the route of internalization of the deiodinase by following the intracellular transit of the affinity-labeled substrate-binding subunit of the deiodinase (p29). Thyroxine rapidly induced the inactivation of the deiodinase and initiated the binding of p29 to F-actin. By 40 min, > 75% of the p29 had been transported to an endosomal pool, which was followed by dissociation of the F-actin-p29 complex. There was no significant accumulation of p29 in the dense lysosomes seen in the presence of thyroxine. In the absence of thyroxine, p29 was internalized and transported to the dense lysosomes at a rate parallel to the inactivation rate of the deiodinase (t1/2 0.75 and 0.64 h, respectively) without involvement with the microfilaments. These data demonstrate that thyroxine targets type II iodothyronine 5'-deiodinase to an endosomal pool by activating specific protein-F-actin interactions involved in microfilament mediated intracellular protein trafficking. PMID- 8444883 TI - Selective regulation of protein kinase C isoenzymes by oleic acid in human platelets. AB - Cis-unsaturated fatty acids activate soluble protein kinase C (PKC) in vitro and in intact platelets. The following studies were conducted to determine the effects of oleate on individual isoenzymes of PKC in human platelets. Human platelets were found to contain predominantly PKC alpha, beta I, beta II, and delta with minor immunoreactivity for PKC epsilon, zeta, and eta. In intact platelets, sodium oleate caused a time-dependent redistribution of PKC alpha, beta II, and delta from cytosol to membrane fractions with little effects on PKC beta I. On the other hand, PMA and thrombin induced translocation of all four isoenzymes of PKC. In vitro, oleate partially activated (50% of Vmax) purified calcium-dependent PKC (alpha, beta I, and beta II) with an EC50 of 50 microM whereas it fully activated (100% of Vmax) purified calcium-independent PKC (predominantly delta) with an EC50 of 5 microM. The selective effects of oleate on PKC isoenzymes were investigated in platelet cytosol which contains endogenous PKC and its physiologic substrates. Under these conditions, oleate potently activated calcium-independent PKC causing the phosphorylation of the 40-kDa substrate. Activation of calcium-dependent isoforms occurred only at higher concentrations of oleate. Thus, oleate activates multiple isoenzymes of PKC with predominant effects on calcium-independent PKC. PMID- 8444884 TI - Differential regulation of human indoleamine 2,3-dioxygenase gene expression by interferons-gamma and -alpha. Analysis of the regulatory region of the gene and identification of an interferon-gamma-inducible DNA-binding factor. AB - The induction of indoleamine 2,3-dioxygenase (IDO) activity has been implicated in the antiproliferative action of interferon (IFN)-gamma on tumor cells and the inhibition of intracellular pathogens. Earlier studies have demonstrated that the expression of the IDO gene is induced strongly by IFN-gamma, but very poorly by IFN-alpha despite the presence of a sequence highly homologous to the IFN-alpha responsive sequence element (interferon-stimulated response element (ISRE)) in its IFN-gamma-responsive control region. In addition, a sequence with a partial homology to the IFN-gamma-responsive sequence (GAS) identified by Lew et al. (Lew, D.J., Decker, T., Strehlow, I., and Darnell, J.E., Jr. (1991) Mol. Cell. Biol. 11, 182-191) in a human gene for a guanylate-binding protein and to the X box sequence found in all major histocompatibility complex class II genes was found. Deletion experiments have indicated that the ISRE homolog (but not the GAS related or the X box-related sequence) was essential for an inducibility by IFN gamma. To investigate the lack of inducibility by IFN-alpha despite the presence of an ISRE homolog, the binding of this ISRE homolog to the IFN-alpha-stimulated gene factor 3 (ISGF3) was examined. Gel mobility shift experiments and competition experiments indicated that this ISRE homolog did not form a stable complex with ISGF3. This may account for a poor inducibility by IFN-alpha. This inability to bind ISGF3 appears to be (at least in part) due to minor differences between the nucleotide sequence of the ISRE homolog present in the IDO gene promoter and the ISRE consensus sequence found in IFN-alpha-inducible genes. An IFN-gamma-inducible DNA-binding factor was identified with characteristics different from ISGF3: (i) the IFN-gamma-inducible factor was detected in the nuclear extracts, but not in the cytoplasmic extracts; and (ii) the appearance of this DNA-binding factor required new protein synthesis, which could explain the dependence on new protein synthesis for the induction of IDO by IFN-gamma. PMID- 8444885 TI - Suppression of a cellular differentiation program by phorbol esters coincides with inhibition of binding of a cell-specific transcription factor (NF-E2) to an enhancer element required for expression of an erythroid-specific gene. AB - Induction by hemin increases, while induction with 12-O-tetradecanoylphorbol-13 acetate (TPA) represses, erythroid-specific gene expression in the human cell line K562. We analyzed the effects of hemin or TPA induction on the binding and activity of transcription factors at a regulatory element found within the transcriptional regulatory sequences of many erythroid-specific genes. TPA induction increases the binding of ubiquitous AP-1 factors to this element. TPA induction inhibits the binding of the lineage limited transcription factor NF-E2 to this transcriptional control element. Hemin induction of K562 cells does not facilitate the binding of NF-E2 to its recognition site. Hemin induction appears to nonspecifically increase the expression of transiently transfected genes in K562 cells. Beyond this nonspecific increase in gene expression, hemin induction acts to increase the activity of the lineage limited transcription factor NF-E2. The divergent effects of hemin and TPA on gene expression in K562 cells are mediated, in part, by their contrasting effects on the transcription factor NF E2. PMID- 8444886 TI - Regulation and properties of extracellular signal-regulated protein kinases 1 and 2 in vitro. AB - Extracellular signal-regulated protein kinases (ERK) 1 and 2 and mutants of each were expressed in bacteria with a hexahistidine tag and purified using nickel chelate chromatography. Basal activity of wild type ERK2 was approximately 2 nmol/min/mg. Self-catalyzed phosphorylation occurred in vitro on the major physiological site of tyrosine phosphorylation in an intramolecular reaction. Rabbit muscle ERK activator activated ERK2 500-1000-fold up to a specific activity (approximately 2 mumol/min/mg) approximating that of ERK1 purified from stimulated cells (Boulton, T.G., Gregory, J.S., and Cobb, M.H. (1991) Biochemistry 30, 278-286). ERK1 could also be activated by the ERK activator to the same extent. Mutants lacking the major site of tyrosine phosphorylation were autophosphorylated at a greatly reduced rate and were no longer highly activated by the ERK kinase. Mutants lacking the major site of threonine phosphorylation were autophosphorylated at the same or an enhanced rate, but the kinase activity of these mutants depended on the residue used to replace the threonine. Replacement by glutamate rendered the kinase capable of being activated by ERK activator, while replacement by alanine did not. Thus, the carboxyl group of glutamate can provide at least some of the features introduced by phosphothreonine in activated ERKs. PMID- 8444887 TI - Iodinated fatty acids as probes for myristate processing and function. Incorporation into pp60v-src. AB - The myristyl group makes a critical contribution to the processing, trafficking, and function of myristylated proteins. A series of [omega-125I]iodo-fatty acids was synthesized in order to elucidate the myristyl group's contribution to the membrane association of pp60v-src, the transforming protein of Rous sarcoma virus. In vitro translation of v-src mRNA was employed to monitor incorporation of myristyl analogs into pp60v-src polypeptide. 12-Iodododecanoic, 13 iodotridecanoic, and 14-iodotetradecanoic acids were selectively incorporated in vitro into pp60v-src. One-dimensional peptide analysis confirmed that the analogs were attached to the N terminus of pp60v-src. Upon addition of membranes, the Src proteins modified by these analogs bound to membranes at levels comparable with or slightly less than the myristyl parent. Myristyl analogs were also shown to be incorporated into pp60v-src in vivo. Fractionation of [omega-125I]iodo-fatty acid labeled cells showed that 12-iododecanoic acid, 13-iodotridecanoic acid, and 14 iodotetradecanoic acid modified pp60v-src associated preferentially with the membrane fractions. These results demonstrate that fatty acyl groups one carbon longer or shorter than myristate can be accommodated within the membrane binding site for pp60v-src and illustrate the utility of in vitro systems for predicting analog behavior in vivo. We anticipate that iodinated fatty acids can be used as tools to aid in clarifying the role of the fatty acid in a variety of myristylated molecules. PMID- 8444888 TI - Monosaccharide and oligosaccharide analysis of proteins transferred to polyvinylidene fluoride membranes after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. AB - We have developed an intermediate method toward the complete carbohydrate analysis of proteins, which should be universally applicable to all proteins and independent of sample matrix. Using only Coomassie Blue-stained proteins which have been electroblotted onto polyvinylidene fluoride membranes, we report a strategy for: (i) determining unequivocally whether a protein is glycosylated; (ii) obtaining a complete monosaccharide composition; (iii) oligosaccharide mapping which separates most forms according to size, charge and isomerity; and (iv) sequentially releasing and analyzing specific classes of oligosaccharides with endoglycosidases. The method was shown to be applicable to a variety of well characterized soluble glycoproteins and to the membrane-bound protein, the gastric H+, K(+)-ATPase. The monosaccharide composition of the H+,K(+)-ATPase revealed the absence of N-acetylneuraminic or N-glycolylneuraminic acids and a monosaccharide composition which indicated O-linked sugar chains. Oligomannosidic/hybrid and biantennary oligosaccharides were sequentially released and analyzed from one electroblotted band of recombinant tissue plasminogen activator using endo-beta-N-acetylglucosaminidase H and endo-beta-N acetylglucosaminidase F2, respectively. Sialylated polylactosamine structures were identified and quantified by analyzing high performance liquid chromatography profiles of oligosaccharides first released by peptide-N4-(N acetyl-beta-D-glucosaminyl)asparagine amidase and then treated with endo-beta galactosidase, using a single, stained band of recombinant erythropoietin. This recombinant erythropoietin was found to contain eight times more tetrasialylated oligosaccharides than previously reported (Sasaki, H., Bothner, B., Dell, A., and Fukuda, M. (1987) J. Biol. Chem. 262, 12059-12076); 47% of released oligosaccharides were identified as polylactosamine structures. PMID- 8444889 TI - Organelle-specific phosphorylation. Identification of unique membrane phosphoproteins of the endoplasmic reticulum and endosomal apparatus. AB - Highly purified endoplasmic reticulum fractions from rat liver and dog pancreas harbor membrane-associated kinases that phosphorylate integral membrane proteins of 90, 56, 35, and 15 kDa with [gamma-32P]GTP and of 90, 56, and 35 kDa with [gamma-32P]ATP. Of these, only the 35-kDa phosphoprotein was N-glycosylated. Screening of Golgi fractions, endosomes, plasma membranes, lysosomes, and mitochondria revealed phosphoproteins unique to each organelle. In particular, endosomes were found to harbor a 48-kDa extrinsic membrane protein and two or more integral membrane phosphoproteins of 30-35 kDa. None of these were N glycosylated as judged by their insensitivity to digestion by N-glycosidase F and a lack of binding to concanavalin A or wheat germ agglutinin. Since the 30-35 kDa membrane phosphoproteins present in Golgi-free endosomal fractions were not detected in endosome-free, highly purified Golgi fractions and were found exclusively in horseradish peroxidase-containing endosomes as determined by the diaminobenzidine shift protocol, then these membrane phosphoproteins are unique to endosomes. Since membrane phosphoproteins unique to the endoplasmic reticulum have been shown to have important functional significance in calcium binding and as a membrane chaperone(s) (Wada, I., Rindress, D., Cameron, P.H., Ou, W.-J., Doherty, J.-J., II, Louvard, D., Bell, A.W., Dignard, D., Thomas, D.Y., and Bergeron, J.J.M. (1991) J. Biol. Chem. 266, 19599-19610; Ahluwalia, N., Bergeron, J.J.M., Wada, I., Degen, E., and Williams, D.B. (1992) J. Biol. Chem. 267, 10914 10918), then the unique endosomal phosphoproteins may serve equally important functions in addition to serving as novel markers for the organelle. PMID- 8444890 TI - Human beta 1-integrin gene expression is regulated by two promoter regions. AB - We report the cloning of two full-length cDNAs coding for the human beta 1 integrin which diverge from each other for their 5'-untranslated sequences. Characterization of a genomic clone containing these two sequences showed that they are contiguous, spaced by 261 nucleotides, and both followed by donor splice sites. Analysis by primer extension and transient transfection in a human osteogenic sarcoma cell line (MG-63) demonstrated the existence of two independent promoters for transcription initiation. The two promoter regions are very G+C-rich, and lack both a TATA box and a CAAT box. Northern blot analysis showed that transcripts starting from the distal promoter (with respect to the first coding exon) are at least 20-fold more abundant than transcripts originating from the proximal one. The levels of both transcripts increase after transforming growth factor-beta 1 induction, however, mRNAs originating from the proximal promoter increase at an higher extent. Reverse transcriptase/polymerase chain reaction analysis performed on different human tissues and cell lines revealed that, while the distal promoter is ubiquitously active, the proximal promoter is not. These findings suggest a possible complex pattern for regulation of the human beta 1-integrin gene expression. PMID- 8444891 TI - Autocrine or paracrine transforming growth factor-beta modulates the phenotype of chick embryo sternal chondrocytes in serum-free agarose culture. AB - Sternal chondrocytes of 17-day-old chick embryos in serum-free agarose culture secrete transforming growth factor-beta. Media conditioned by such cells prevent serum-induced chondrocyte hypertrophy and cause a phenotypic modulation in serum free culture which is similar to that observed for chondrocytes in monolayer culture. The modulated cells lose the round shape of differentiated chondrocytes and increasingly with time resemble tendon fibroblasts embedded into agarose. In addition, they produce less matrix macromolecules which include collagen I rather than cartilage collagens II, IX, X, and XI. All of these effects are abolished upon addition to the conditioned media of a monoclonal antibody against recombinant human transforming growth factor-beta 2. The same factor caused effects closely similar to those elicited by conditioned media. Therefore, the phenotypic modulation in adhesion-dependent cultures of chondrocytes in vitro does not directly result from cell-matrix interactions but can be produced also in suspension culture under the direction of appropriate diffusible stimuli that include transforming growth factor-beta. In addition, the results support the concept of transforming growth factor-beta as a multifunctional cytokine acting differently on cells of the same developmental origin depending on their stage of differentiation. PMID- 8444892 TI - A variant form of the type C atrial natriuretic peptide receptor generated by alternative RNA splicing. AB - A novel form of type C atrial natriuretic peptide receptor (ANP-C) was identified, characterized, and shown to be a product of alternative RNA splicing. Sequencing of several clones of ANP-C cDNA isolated from a bovine lung cDNA library revealed the presence of a new clone encoding a 536-amino acid ANP-C. The nucleotide sequence of this novel clone is very similar to that of the previously cloned ANP-C which consists of 537 amino acids. The sole difference between the two clones is the presence or absence of a very short segment of only 3 base pairs (bp), by which the sequence Ser472-Gly473 of the longer form is changed to Cys472 in the variant form; the other regions are identical. Alignment of the cDNA sequences with that of the ANP-C gene indicated that the two forms of ANP-C receptor arise from a single gene by alternative splicing using one donor and two closely located acceptor sites. Biochemical and pharmacological characterization using a mammalian cDNA expression system indicated that the two variants are similar in their subunit structures, in ligand-binding properties, and even in internalization kinetics. Polymerase chain reaction amplification of the transcripts demonstrated that 1) although the novel form is a minor species, it is present in various tissues such as the lung, kidney, adrenal, and vascular smooth muscle and endothelial cells and 2) the ratio of the novel variant form to the original longer form remains almost constant in these tissues. The alternative splicing reported here contributes to the diversity of ANP receptors; however, its physiological significance remains to be clarified. PMID- 8444893 TI - Iron specificity of the Fur-dependent regulation of the biosynthesis of the manganese-containing superoxide dismutase in Escherichia coli. AB - The Fur protein, which regulates iron uptake in Escherichia coli, also represses the biosynthesis of the manganese-containing superoxide dismutase (MnSOD). A strain of E. coli bearing a lacZ fusion to the aerobactin operon was used to compare the metal specificities of the regulation of MnSOD and of aerobactin by Fur. Iron, but not manganese, acted as a corepressor of the Fur-dependent inhibition of MnSOD biosynthesis. The iron-mediated inhibition of MnSOD biosynthesis was dependent upon an intact fur locus, indicating that the effect of iron is mediated by the fur gene product. The suppression of the accumulation of MnSOD by iron, but not by manganese, was not due to destabilization of the MnSOD polypeptide by iron. Thus this effect of iron was also seen in a sodA::lacZ operon fusion in which the production of beta-galactosidase was regulated by the sodA promoter. In contrast, both iron and manganese served as corepressors of aerobactin biosynthesis. It thus appears that the effectiveness of specific metal cations to act as corepressors with Fur varies with the gene being regulated by the Fur-metal complex. PMID- 8444894 TI - Oligomerization of immunoglobulin G heavy and light chains in vitro. A cell-free assay to study the assembly of the endoplasmic reticulum. AB - A biochemical assay to study the assembly of the endoplasmic reticulum (ER) in a cell-free system is introduced. Incubation in vitro of ER vesicles containing only immunoglobulin gamma 1 heavy (H) chains with ER vesicles containing only K light (L) chains results in fusion and oligomerization of the H and L chains to form the H2L2 complex (immunoglobulin G). ER fusion/H2L2 oligomerization is time and temperature dependent and requires energy in the form of ATP. It is stimulated by the addition of cytosol and requires protease-sensitive components present on the membranes. The addition of guanosine 5'-O-(thiotriphosphate) inhibits membrane fusion and subsequent H2L2 oligomerization without affecting the assembly of H2L2 from detergent-solubilized pools, suggesting an important role for GTPases in vesicle recognition or fusion. The development of a rapid and quantitative assay to study the assembly of the ER in a cell-free system will allow us to identify components involved in the recognition, fusion, and post fusion events critical for ER function in vivo. PMID- 8444895 TI - Effect of human biliary immunoglobulins on the nucleation of cholesterol. AB - We have previously identified that either biliary immunoglobulin IgA or IgM is a pronucleating protein which can accelerate the precipitation of cholesterol from bile. In this study we purified the biliary immunoglobulins (IgA, IgG, and IgM) to homogeneity by affinity chromatography to investigate the relative cholesterol nucleating potency of each immunoglobulin. Each immunoglobulin was added to slow nucleating heated abnormal biles in a dose-response manner to give a final concentration of protein in the range of 62.5-625 micrograms/ml bile. Cholesterol nucleating activity was measured by noting the first day of cholesterol crystal formation as well as the number of crystals formed over the observation period. Biliary IgM and IgG appear to be more potent pronucleators than IgA. Isolated serum IgM from patients with Waldenstrom's macroglobulinemia as well as serum IgG from patients with and without cholesterol gallstones were shown to have pronucleating activity and acted in a dose-response manner. Commercial IgG unlike commercial IgM retains nucleating activity. The concentration of biliary immunoglobulins was measured by an enzyme-linked immunoassay (ELISA) in the gallbladder bile of patients with and without cholesterol gallstones. Biliary IgG concentrations in bile were higher in cholesterol gallstones patients than in pigmented gallstone patients and controls. We conclude that immunoglobulins particularly IgG and IgM are important pronucleating proteins and could play a role in the pathogenesis of cholesterol gallstones. PMID- 8444896 TI - Membrane topology and biogenesis of eukaryotic signal peptidase. AB - The signal peptidase complex (SPC) is a hetero-oligomeric membrane protein containing subunits of 12, 18, 21, 22/23, and 25 kDa. The 18- and 21-kDa subunits are mammalian homologs of SEC11 protein, which is necessary for signal peptide processing and cell viability in the yeast Saccharomyces cerevisiae. The functional and/or structural contributions of the 12-, 22/23-, and 25-kDa subunits to SPC activity have not yet been elucidated. To explore the structure of SPC subunits and their relationships to signal peptide processing and protein translocation, we have examined their endoplasmic reticulum (ER) membrane topology and biogenesis. Signal peptidase activity and SPC subunits are resistant to protease treatment in intact and detergent-solubilized membranes. Heat denatured SPC subunits and SPC subunits translated in vitro are, however, protease sensitive, suggesting that the assembly of the oligomeric complex confers protease resistance. To define the membrane topology of SPC subunits, both wild-type subunits and subunit fusion proteins containing additional sites for N-linked glycosylation were assembled into microsomal membranes in vitro. Despite the presence of multiple hydrophobic domains, each subunit is anchored to the ER membrane by a single amino-terminal transmembrane domain in an Ncytoplasmic Cexoplasmic (type II) orientation. This topology places the bulk of the protein mass in the ER lumen and positions a putative serine-containing active site domain in SPC 18 and 21 at the same relative distance from the membrane as the analogous region in Escherichia coli leader peptidase. These studies have also revealed that, in spite of the temporal and perhaps physical association of the SPC with the process of protein translocation, SPC subunits integrate into the ER membrane by a signal recognition particle-dependent pathway and, hence, rely on the existence of a preformed translocation apparatus for their own membrane assembly. PMID- 8444897 TI - Hexokinase II mRNA and gene structure, regulation by insulin, and evolution. AB - A DNA segment that is highly conserved in glucokinase (hexokinase IV) and hexokinase I cDNA was used to identify specific cDNAs in a library prepared from rat adipose tissue mRNA. Some of these cDNAs were identified as being hexokinase I cDNA. Others, although similar to both the glucokinase and hexokinase I cDNAs, were unique. Two of these unique cDNAs overlapped and contained an open reading frame that encoded a protein of 103 kDa which, when expressed in Escherichia coli, had kinetic properties characteristic of hexokinase II. The entire hexokinase II mRNA sequence and the exon-intron structure of the hexokinase II gene were determined. A single transcription initiation site and two distinct termination sites account for the two observed hexokinase II RNA species of 5500 and 4400 nucleotides that were detected when either of the cDNAs was used as a hybridization probe against poly(A)+ RNA isolated from rat adipose tissue. Hexokinase II mRNA was decreased in adipose tissue from diabetic rats, but was restored by insulin treatment to levels found in nondiabetic control rats. Insulin also induced hexokinase II mRNA in two adipose cell lines (3T3-F442A and BFC-1B) and two skeletal muscle cell lines (C2C12 and L6). In L6 cells, this increase was accounted for by a corresponding increase of hexokinase II gene transcription. Comparison of the structures of the hexokinase II and glucokinase genes support the hypothesis that the 100-kDa hexokinase arose by gene duplication and tandem ligation of a 50-kDa glucokinase-like ancestral gene. PMID- 8444898 TI - Cell adherence to fibronectin and the aggregation of the high affinity immunoglobulin E receptor synergistically regulate tyrosine phosphorylation of 105-115-kDa proteins. AB - Adherence of cells to extracellular matrix components modulates cellular responses. Here we compared the array of tyrosine phosphorylated proteins induced by the aggregation of the high affinity receptor for IgE (Fc epsilon RI) in fibronectin-adherent and in nonadherent rat basophilic leukemia (RBL-2H3) cells. Adherence to fibronectin in the absence of Fc epsilon RI aggregation induced tyrosine phosphorylation of 105-115-kDa proteins. This phosphorylation was reversed by EDTA and by a synthetic peptide containing the sequence Arg-Gly-Asp, demonstrating a requirement for fibronectin-integrin interaction. Aggregation of Fc epsilon RI in fibronectin-adherent cells markedly enhanced the tyrosine phosphorylation of the same 105-115-kDa proteins. There were minimal differences in tyrosine phosphorylation of other proteins induced by the aggregation of Fc epsilon RI in nonadherent and in fibronectin-adherent cells. Direct activation of protein kinase C and/or increase in calcium influx induced the phosphorylation of the 105-115-kDa proteins only in fibronectin-adherent cells. The magnitude of the phosphorylation of the 105-115-kDa proteins induced by the aggregation of Fc epsilon RI in fibronectin-adherent cells was substantially greater than the sum of that due to adherence to fibronectin and the aggregation of Fc epsilon RI in nonadherent cells. Therefore, cell adherence and the aggregation of Fc epsilon RI synergistically regulate tyrosine phosphorylation of the 105-115 kDa proteins. PMID- 8444899 TI - Complete primary structure of a sea urchin type IV collagen alpha chain and analysis of the 5' end of its gene. AB - We isolated several overlapping cDNAs from Strongylocentrotus purpuratus coding for a nonfibrillar collagen chain structurally homologous to the vertebrate type IV collagen chains and arbitrarily termed 3 alpha chain. The deduced amino acid sequence of the sea urchin polypeptide includes a 28-residue signal peptide, a 14 residue amino-terminal non-collagenous segment, a triple-helical domain of 1390 residues containing 23 imperfections, and a 226-residue carboxyl-terminal non collagenous region. Comparison of the sea urchin amino- and carboxyl-terminal non collagenous domains with those of the vertebrate type IV collagen chains indicated a high level of sequence identity to the alpha 1 (IV) and alpha 5 (IV) chains. This evolutionary relationship was further strengthened by the analysis of the genomic organization of the 5' portion of the sea urchin gene, which also provided the composition of some of the upstream sequences. In addition, this work demonstrated that our gene product is identical to that encoded by the partial cDNA clone recently isolated by others (Wessel, G. M., Etkin, M., and Benson, S. (1991) Dev. Biol. 148, 261-272) who demonstrated its involvement in the biomineralization process of cultured mesenchyme cells. PMID- 8444900 TI - Identification of metal-isocitrate binding site of pig heart NADP-specific isocitrate dehydrogenase by affinity cleavage of the enzyme by Fe(2+)-isocitrate. AB - The divalent metal-isocitrate site of pig heart NADP-specific isocitrate dehydrogenase can be located by affinity cleavage of the enzyme by Fe(2+) isocitrate in the presence of O2, in analogy to the "chemical nuclease" action of DNA-binding drugs linked to Fe-EDTA. The enzyme is irreversibly inactivated and cleaved by Fe(2+)-isocitrate more rapidly than by Fe2+. Mn2+ prevents inactivation and cleavage by Fe(2+)-isocitrate or by Fe2+. Furthermore, other tri or dicarboxylates (such as citrate, tricarballylate, or malate), which are not effective substrates of the enzyme, fail to promote inactivation and cleavage of the enzyme by Fe2+. These results indicate that the oxidative inactivation and cleavage reactions are specific. Two pairs of major peptides are generated during Fe(2+)-isocitrate inactivation: 30 + 17 kDa and 35 + 11 kDa, as compared with 46 kDa for the intact enzyme. NH2-terminal sequencing revealed that these peptides arise by a mutually exclusive cleavage at either Asp253-Met254 or His309-Gly310, suggesting Asp253 and His309 as coordination sites for Fe(2+)-isocitrate and, by implication, for Mn(2+)-isocitrate. Fe2+ alone produces peptides (32 + 15 kDa) by an alternate specific cleavage between Tyr272 and Asp273, consistent with free metal ion occupying a different site from metal-isocitrate in NADP-dependent isocitrate dehydrogenase. Affinity cleavage may be a generally useful method for locating metal and metal-substrate sites in enzymes. PMID- 8444901 TI - Identification of a novel cell attachment domain in the HIV-1 Tat protein and its 90-kDa cell surface binding protein. AB - The HIV-1 transactivator protein Tat is essential for viral gene expression and replication. Tat is taken up by cells and transactivates the HIV-LTR promoter in the cell nucleus. The present studies show that cells adhere to both synthetic and recombinant Tat, and, using synthetic peptides, we localize the binding site to a region spanning amino acid residues 49-57 (peptide Tat49-57). Tat49-57 also inhibited cell attachment to solid phase full-length Tat peptide and to recombinant Tat protein. Using Tat peptide affinity chromatography, we identified a 90-kDa cell surface protein that binds to Tat. The 90-kDa protein could be eluted from the Tat column using the Tat49-57 peptide. A 90-kDa cell surface Tat binding protein was also identified by coprecipitation with Tat after incubation with radiolabeled cell membrane preparations. Co-precipitation of the 90-kDa protein was inhibited by competition with a Tat49-65 peptide, but not with Tat55 86. Our findings suggest that cellular attachment to Tat is mediated through a 90 kDa cell surface protein that binds to a Tat domain between amino acids 49 and 57. PMID- 8444902 TI - Functional complementation of staphylococcal alpha-hemolysin fragments. Overlaps, nicks, and gaps in the glycine-rich loop. AB - The final steps in assembly of the lytic pore formed by staphylococcal alpha hemolysin (alpha HL) involve the formation of a nonlytic oligomeric pore precursor, followed by the formation of a transmembrane channel. In this study, truncation mutants of alpha HL encompassing the NH2-terminal or COOH-terminal half of the polypeptide chain and all, part, or none of the central glycine-rich loop were obtained by in vitro, coupled transcription and translation of mutant plasmid DNAs. These polypeptides were unable to oligomerize upon or cause lysis of rabbit erythrocytes (rRBCs). Twenty-one pairs of the same truncation mutants constituting discontinuous alpha HL chains with overlaps, nicks, and gaps in the central loop were obtained by cotranslation. When incubated with rRBCs, many of the pairs were able to form hetero-oligomers with wild-type alpha-hemolysin (s alpha HL) and most of these formed homo-oligomers in the absence of s-alpha HL. However, only members of a subset of these pairs were able to lyse the cells. The lytic combinations contained overlaps, nicks, or gaps, but only two pairs, with nicks between amino acid residues 128 and 129 and between 131 and 132 had hemolytic activities approaching that of the wild-type polypeptide. Active combinations could also be obtained by separately translating NH2- and COOH terminal truncation mutants and then combining them. These findings suggest that the integrity of the central loop is of little significance for oligomer formation but that it is more important for the final step in pore assembly or alternatively for determining the correct structure of the conductive channel. Our findings disagree with previous reports of NH2- and COOH-terminal fragments with hemolytic activity and of the prevention of hemolysis by proteolytic cleavage in the central loop. This discord is attributed to experimental and interpretative ambiguities in the earlier protein chemistry. For example, we show that loss of hemolytic activity after treatment with trypsin is not due to cleavage after Lys-131, as previously proposed, but to the removal of a small NH2 terminal peptide through cleavage after Lys-8. PMID- 8444903 TI - Characterization of single-chain antibody (sFv)-toxin fusion proteins produced in vitro in rabbit reticulocyte lysate. AB - Chimeric proteins consisting of a fusion between binding-deficient mutants of diphtheria toxin (DT) or Pseudomonas exotoxin A (PE) and a single-chain antibody (E6 sFv) against the human transferrin receptor (TfnR) were expressed in a rabbit reticulocyte lysate system. Molecules utilizing PE40 (the carboxyl terminus 40 kDa of PE, lacking the binding domain) exhibited significant E6 sFv-mediated, cell type-specific cytotoxicity (IC50 1 x 10(-10) M) against a human erythroleukemia-derived cell line, K562. In contrast, a fusion protein between the same sFv and a DT mutant, DTM1 (containing two amino acid substitutions in the binding domain [S(508)F, S(525)F]) was not significantly cytotoxic, despite being enzymatically active. A tripartite protein in the form NH2-DTM1-E6 sFv-PE40 COOH exhibited cytotoxicity comparable to that of the PE40-sFv fusion (IC50 1 x 10(-10) M), suggesting that the deficit in activity of DTM1-sFv is not a function of misfolding of the sFv moiety or of a reduced ability to bind TfnR. In contrast to DTM1-E6 sFv, a fusion protein between a second DT mutant, CRM 107 [S(525)F], and the E6 sFv was specifically cytotoxic (IC50 1 x 10(-9) M), and toxicity could be blocked by addition of excess E6 antibody. The cell-free in vitro expression system we describe is rapid and may be used to express functional toxin-sFv fusion proteins. No protein refolding procedures are required, and the technique may be used to express proteins which, due to restrictions imposed on manipulation of toxin-encoding genes in Escherichia coli, could not be produced by more conventional methods. PMID- 8444904 TI - Caltrin, the calcium transport regulatory peptide of spermatozoa, modulates acrosomal exocytosis in response to the egg's zona pellucida. AB - Acrosomal exocytosis is initiated in mammalian sperm by stimulatory agonists in the zona pellucida. Recently, it was shown that exocytosis is modulated in bovine sperm by extrinsic factors present in seminal fluids (Florman, H.M., and First, N.L. (1988) Dev. Biol. 128, 464-474). Fractionation of bovine seminal fluids yields a M(r) approximately 6,500, basic (pI approximately 8.5) peptide that accounts for the positive modulation of zona pellucida-induced acrosome reaction (ED50 and maximal response at 0.2 and 1 micrograms/ml, respectively). In addition, application of purified peptide to fura 2-loaded, cauda epididymal sperm supported zona pellucida-promoted elevations of Ca2+i equivalent to those observed with sperm treated with unfractionated seminal fluids in vitro or in vivo. Finally, peptide treatment regulated gamete interaction in a manner consistent with the distinct behaviors of cauda epididymal and ejaculated bovine sperm. This purified seminal peptide was identified by sequence analysis as caltrin, a previously characterized regulator of Ca2+ transport in bovine sperm. We therefore propose that caltrin is a regulator of sperm signal transduction pathways activated by zona pellucida binding. PMID- 8444905 TI - Suppression of platelet-derived growth factor receptor tyrosine kinase activity by unsaturated fatty acids. AB - Treatment of cells with platelet-derived growth factor (PDGF) was previously shown to increase the release of unesterified fatty acids from phospholipids. In view of these observations we examined the effect of various fatty acids on PDGF receptor activity. Unsaturated (oleic, linoleic, linolenic, and arachidonic) but not saturated (stearic and arachidic) fatty acids significantly inhibited the tyrosine kinase activity of the PDGF receptor in intact cells and membrane preparations. Half-maximal inhibition (IC50) was observed between 60 and 100 microM and maximal inhibition between 170 and 200 microM. Lysophospholipids and phospholipids had no effect on receptor activity. Activation of endogenous phospholipase A2 by mellitin in vivo or hydrolysis of phosphatidylcholine by purified phospholipase A2 in vitro inhibited PDGF receptor autophosphorylation similar to that of purified fatty acids. Dimerization of PDGF receptors in vivo was significantly reduced by concentrations of arachidonic acid inhibitory for receptor kinase activity while the binding of PDGF was only marginally affected. These data suggest a possible feedback mechanism resulting in the reduction of PDGF receptor activity by unsaturated fatty acids generated downstream within the PDGF-dependent signal transduction pathway and this effect may be as a direct result of decreased receptor dimerization and/or kinase activity. PMID- 8444906 TI - Mutations in the helix-turn-helix motif of the Escherichia coli UvrA protein eliminate its specificity for UV-damaged DNA. AB - The Escherichia coli UvrA protein possesses a stretch of amino acids, 494 to 513, that matches the consensus sequence of the helix-turn-helix motif of many sequence-specific DNA binding proteins. It also has two zinc finger motif regions and two ATP binding sites. To study the potential roles of both helix-turn-helix and zinc finger motifs in the functioning of UvrA protein, random mutations were created in these motif regions by degenerate oligonucleotide-directed mutagenesis. Using this method, 12 single substitution mutants (eight in the helix-turn-helix motif region, one in the N-terminal zinc finger region, and three in the C-terminal zinc finger region) were isolated that failed to confer UV resistance in the E. coli strain deleted of the uvrA gene. One "hyper" UV resistant mutant, G275A, was identified that conferred significantly more UV resistance than the wild type in the MH1-delta A strain. To further investigate the mechanism of failure of these mutant UvrA proteins to support nucleotide excision repair, two mutant UvrA proteins, G502D and V508D, were selected for purification and characterization, since they carry mutations at the positions offered as the putative constellation for the helix-turn-helix motif. The binding affinity of these two mutants for nonirradiated plasmid DNA was unaffected by the mutations. Both mutant proteins exhibited substantial ATPase activity, and together with the UvrB protein, they were capable of generating positively supercoiled plasmid DNA from the relaxed form in the presence of ATP and bacterial topoisomerase I. However, both mutant proteins failed to respond to UV damage in the filter binding assay and were incapable of forming 2 x SSC resistant nucleoprotein complexes with UvrB protein on UV-irradiated plasmid DNA. Taking these properties together, it appears that the mutations in the helix-turn helix motif region impaired the UvrA protein's ability to recognize UV damage, while its other activities were largely unaffected. Interestingly, ERCC-3, a human DNA repair protein, also has a similar helix-turn-helix motif. Given the highly conserved nature of repair proteins in general, this observation raises the possibility that both procaryotes and eucaryotes might use similar mechanisms to recognize damaged sites in their genomes. PMID- 8444907 TI - In vivo analysis of the murine beta-myosin heavy chain gene promoter. AB - The 5' upstream region of the murine beta-myosin heavy chain (MHC) gene has been isolated and tested for its ability to drive gene expression in transgenic mice. Three classes of transgenic mice were generated. The constructs contained approximately 5000, 2500, and 600 base pairs of beta-MHC upstream sequence fused to the chloramphenicol acetyltransferase gene and were termed beta 5, beta 2.5, and beta .6, respectively. Muscle-specific expression was observed with all three constructs. However, only the beta 5 lines directed high levels of muscle specific transgene expression in both pre- and postbirth mice. Expression driven by the two shorter constructs was two to three orders of magnitude lower when the chloramphenicol acetyltransferase specific activities were compared. These data suggest that a distal-positive element directs high levels of gene expression in the ventricle and in slow skeletal muscles. Analyses of transgene expression during heart maturation revealed that some of the beta 5 lines were not able to respond in an appropriate manner to developmental transcriptional cues. Unlike the endogenous beta-MHC gene, which is down regulated in the ventricles around the time of birth, reporter gene expression in the majority of the lines generated was not shut off in the ventricles of the adult animals. These data indicate that high levels of muscle-specific beta-MHC gene expression are dependent upon the combinatorial interactions of a number of sequence elements that are distributed over a large region of the gene's upstream sequence. PMID- 8444908 TI - Measurements in the conduct of research. PMID- 8444909 TI - The hospital cost of total hip arthroplasty. A comparison between 1981 and 1990. AB - The change in the hospital cost of total hip arthroplasty over a ten-year period at the Lahey Clinic was evaluated by comparison of the hospital bills for forty four hip replacements that had been performed in 1981 with the bills for 104 such operations that had been done in 1990. Each hospital charge was converted to cost with use of government-mandated hospital-specific cost-to-charge ratios. The average actual hospital cost for total hip arthroplasty increased 46.5 per cent, from $8428 in 1981 to $12,348 in 1990. However, in inflation-adjusted dollars, the cost increased only 1.9 per cent. During this period, the cost for a patient room decreased from 50 per cent of the hospital cost in 1981 to 37 per cent of the hospital cost in 1990. In sharp contrast, the cost of hip prostheses increased from 11 per cent of the hospital cost in 1981 to 24 per cent of the hospital cost in 1990. The actual dollar cost of the hip prostheses increased 212 per cent, and the inflation-adjusted dollar cost increased 117 per cent. The hospital cost of total hip arthroplasty during the 1980's was controlled by decreases in the length of stay in the hospital and in the volume of services delivered. The unit costs of supplies and, specifically, the cost of hip prostheses were not controlled. In the 1990's, efforts to control the hospital cost of total hip arthroplasty must concentrate on decreasing the cost of the prostheses and on controlling the unit costs of personnel and of hospital supplies. PMID- 8444910 TI - Exposure of the orthopaedic surgeon to radiation. AB - A prospective study of sixty-five orthopaedic procedures performed with fluoroscopic assistance was undertaken to determine the risk to the primary orthopaedic surgeon with regard to radiation. Radiation was monitored with the use of a universal film badge placed outside the collar of a lead apron, and a gas-sterilized thermoluminescent dosimeter ring worn on each hand. The rings were changed with every operation, but the same film badge was transferred from surgeon to surgeon. The hand dominance of the surgeon, the duration of the operative procedure, the type of operation, and the total time that fluoroscopy had been used were noted. The study was conducted during twenty-one intramedullary nailing procedures (thirteen involving distal locking), forty open reductions with internal fixation (plates and screws), and four external-fixation procedures. All of the badges and rings were submitted for a report regarding radiation exposure. No relationship was found between a ring with a positive reading for exposure to radiation and the duration of the operation. Similarly, there was no correlation between a positive reading and the surgeon's hand dominance. The mean duration of the fluoroscopy was 2.3 minutes for the group for which the rings did not show a positive reading and 4.7 minutes for the group for which the rings did show a positive reading. This was a significant difference (p < 0.0001). There was no positive reading for exposure to radiation from any ring that had been worn during a procedure in which the fluoroscope had been used for less than 1.7 minutes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444911 TI - Late complications of fractures of the calcaneus. AB - We retrospectively reviewed the results of the operative treatment of forty-three fractures of the calcaneus in forty-two patients (thirty-six men and six women). The operations had been performed a mean of twenty-six months (range, six to seventy-two months) after the injury. An in situ subtalar arthrodesis had been performed in fifteen patients; a subtalar distraction bone-block arthrodesis, in fourteen; a triple arthrodesis, in five; a lateral calcaneal ostectomy, in seven; a transection and proximal transposition of the sural nerve, in seven; and a release of the tibial nerve, in five. The patients were examined at a mean of thirty-two months (range, twenty-six to fifty-two months) after the operation. The difference between the preoperative and postoperative rating scores was used to measure any improvement in function. Pain was partially relieved in thirty eight (90 per cent) of the patients, function improved in thirty-five (83 per cent), and thirty-two (76 per cent) of the patients returned to work or to a pre injury level of activity at a mean of eight months (range, four to sixteen months) after the operation. There was a trend (p = 0.07) that the longer the interval between the injury and the operation, the longer the subsequent interval until the patient returned to full activities or work. The most successful results were in the patients who had had a subtalar arthrodesis. PMID- 8444912 TI - Intra-articular fractures of the calcaneus. A critical analysis of results and prognostic factors. AB - Forty-four patients who had had fifty-two calcaneal fractures were managed with open reduction and internal fixation. The results were reviewed retrospectively, between four and fourteen years after the operation, with use of an evaluation system for the hindfoot and with plain radiographs. The characteristics of the patients that were associated with an unsatisfactory outcome were an age of more than fifty years, a greater body weight, work involving strenuous labor, and increased time missed from work due to the injury. Other prognostic variables associated with an unsatisfactory result included subtalar incongruity, osteoarthrosis of the talonavicular joint and the ankle, an increased heel width, a decreased fibulocalcaneal space, and a decreased Bohler-angle ratio of the fractured to the normal side. The heel height, fat-pad height, arch angle, talocalcaneal angle, and length of the Achilles-tendon fulcrum were not related to the outcome. Patients who had had a tongue-type fracture had a better result than those who had had a central depression fracture, while those who had had a central depression fracture had a better outcome than those who had had a comminuted fracture. Comminution of tongue and large central-depression fractures was associated with a worse prognosis. The most common most painful area in the patients who had a satisfactory outcome was the lateral aspect of the hindfoot, while in those who had an unsatisfactory result, it was the heel pad. PMID- 8444913 TI - Triple arthrodesis in older adults. Results after long-term follow-up. AB - We studied the results for seventeen patients (eighteen feet) who had had a triple arthrodesis at an average age of sixty-six years (range, fifty-two to eighty years). There were twelve women and five men. The procedures had been performed to correct deformities of the hindfoot and midfoot caused by an untreated rupture of the posterior tibial tendon in ten patients; by rheumatoid arthritis in three patients (four feet); and by neuropathic arthropathy (associated with diabetes mellitus), trauma, old poliomyelitis, and a stroke in one patient each. The average duration of follow-up was forty-two months (range, twenty-seven to 156 months). At the most recent follow-up examination, three patients had a non-union (one, of the talonavicular joint and two, of the calcaneocuboid joint), six patients (seven feet) had progressive degenerative joint disease involving the ankle, seven had progressive degenerative changes in the mobile joints of the feet, two had had an infection but both infections had healed, and one had had postoperative collapse of the foot because of premature, unauthorized weight-bearing. In one patient, a staple across the subtalar joint had been removed because of pain caused by impingement of the staple on the tip of the fibula. Over-all, fourteen of the seventeen patients were satisfied with the result of the operation. All seventeen had less pain postoperatively, but eleven still had some discomfort.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444914 TI - Reinfusion of shed blood after orthopaedic procedures in children and adolescents. AB - A prospective study was done of the results of infusion of drained blood after major procedures on the spine and hip in twenty-six patients. The Solcotrans system was used to salvage drained blood in the first six hours after the operation. Transfusion requirements, blood loss, hematocrit, temperature, prothrombin time, partial prothrombin time, platelet count, results of blood cultures, and levels of factor VIII, factor V,D-dimer, antithrombin III, plasminogen, protein C, and complement C3a des arginine were determined for some or all of the patients. A mean of 375 milliliters of blood from the Solcotrans receptacle was reinfused. All of the cultures were negative. There were no febrile reactions. The mean values for the specimens of the salvaged blood were: hematocrit, 0.20; hemoglobin, seventy-one grams per liter; plasma hemoglobin, 2.36 grams per liter; C3a des arginine, 9.4 x 10(-3) grams per liter; fat particles of less than nine micrometers in diameter, 23,643 per milliliter; and D dimer, 205 x 10(-3) grams per liter. Studies of blood samples that were collected from patients one to two hours and twelve to eighteen hours after the transfusion showed only slight increases in fibrin split products one hour after the transfusion; these values reverted to normal by eighteen hours. No clinical coagulopathy associated with reinfusion was observed. The reinfusion of unwashed, filtered shed blood that was as much as 15 per cent of the total blood volume proved to be a safe technique after major orthopaedic procedures. PMID- 8444915 TI - Scapulothoracic arthrodesis in facioscapulohumeral muscular dystrophy. Review of seventeen procedures with three to twenty-one-year follow-up. AB - The scapula was fixed to the ribs in twelve patients who had facioscapulohumeral muscular dystrophy, in order to provide stability for activities involving the upper limbs. The duration of follow-up ranged from three to twenty-one years. Abduction, in 30 degrees of flexion, improved an average of 60 degrees, and gains in strength for carrying and lifting were reported by the patients. Complications included a brachial plexus palsy, which resolved, and a frozen shoulder. All of the patients but one were pleased with the result. PMID- 8444916 TI - Direct in vitro measurement of forces in the cruciate ligaments. Part I: The effect of multiplane loading in the intact knee. AB - Specially designed load-transducers that measured the resultant forces exerted by the posterior and anterior cruciate ligaments on their respective femoral and tibial insertions were applied to eighteen fresh-frozen cadaveric knees for a series of controlled loading experiments. The mean force in the posterior cruciate ligament at 5 degrees of forced hyperextension of the knee was 23 per cent of the mean force in the anterior cruciate ligament. When the knee was hyperflexed by application of 10.0 newton-meters of bending moment to the tibia, the mean force in the posterior cruciate ligament was 55 per cent of that in the anterior cruciate ligament. Quadriceps tendon pull increased the force in the posterior cruciate ligament in twelve of the fourteen specimens to which it had been applied, at 80 and 90 degrees of flexion only. The force generated in the posterior cruciate ligament by applied internal tibial torque was greatest when the knee was in 90 degrees of flexion; the force in the anterior cruciate ligament was greatest when the knee was fully extended. External tibial torque generated force in the posterior cruciate ligament in only eight specimens, and only at 80 and 90 degrees of flexion. The levels of force that were generated in the posterior cruciate ligament by applied varus and valgus bending moment were greatest at 90 degrees of flexion of the knee; the levels of force in the anterior cruciate ligament were greatest with the knee in full extension. With the knee flexed 90 degrees and the tibia in neutral rotation, fifty newtons of applied posterior tibial force increased the mean force in the posterior cruciate ligament by 58.4 newtons; at full extension, no increase in the force in the ligament was recorded, indicating that tensed capsular structures were absorbing the applied load. When the tibia was internally or externally rotated by applied tibial torque, the increases in the force in the ligament from applied posterior tibial force were sharply diminished. PMID- 8444917 TI - Direct in vitro measurement of forces in the cruciate ligaments. Part II: The effect of section of the posterolateral structures. AB - Specially designed load-transducers were applied to eight fresh-frozen cadaveric knee specimens in order to measure resultant forces in both cruciate ligaments as the knees were subjected to straight varus-valgus bending moment and to tibial torque (with and without a superimposed posterior tibial force). The forces in the ligaments and tibial rotation were recorded at seven angles of flexion of the knee, between 0 and 90 degrees, before and after section of the posterolateral structures. Ligamentous section increased angulation of the tibia when varus moment was applied to the knee; the large increases in lateral opening of the knee joint were accompanied by increases in the force in the anterior cruciate ligament at all angles of flexion and increases in the force in the posterior cruciate ligament between 45 and 90 degrees of flexion. When valgus moment was applied, there were no significant changes in valgus angulation or the resultant force in either cruciate ligament after ligamentous section. Ligamentous section increased rotation of the tibia when external torque was applied to the knee. The increased external rotation was accompanied by decreases in the force in the anterior cruciate ligament between 0 and 20 degrees of flexion of the knee and increases in the force in the posterior cruciate ligament between 45 and 90 degrees of flexion. In the studies involving applied internal tibial torque, after ligamentous section, rotation of the tibia increased slightly between 60 and 90 degrees of flexion. The force in the anterior cruciate ligament increased between 0 and 20 degrees of flexion, while the force in the posterior cruciate ligament was unaffected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444918 TI - Diagnosis of occult fractures about the hip. Magnetic resonance imaging compared with bone-scanning. AB - Sixty-two consecutively seen patients in whom a fracture about the hip was clinically suspected, but in whom the radiographic findings were negative, were examined with both magnetic resonance imaging and bone-scanning. The magnetic resonance-imaging studies, consisting of T1-weighted coronal sections, were done within twenty-four hours after admission to the hospital, and the bone scans, within seventy-two hours after admission. There were twenty-three men and thirty nine women. Thirty-six patients who had evidence of a fracture on the magnetic resonance-imaging study also had a positive bone scan initially. Twenty-three patients who had a negative finding on the magnetic resonance-imaging study had a corresponding negative bone scan. Two additional patients had evidence of avascular necrosis of the femoral head on both the magnetic resonance image and the bone scan, and they were managed non-operatively. One patient had a positive magnetic resonance image and a negative bone scan twenty-four hours after admission. A repeat bone scan, which was made six days later, was positive for a fracture of the femoral neck and the patient was managed with internal fixation. Magnetic resonance imaging was as accurate as bone-scanning in the assessment of occult fractures of the hip. The magnetic resonance imaging took less than fifteen minutes to perform, and it was tolerated well by the patient. Magnetic resonance imaging provides an early diagnosis of occult fractures about the hip and may decrease the length of the stay in the hospital by expediting definitive treatment. PMID- 8444919 TI - The Miller-Galante knee prosthesis for the treatment of osteoarthrosis. A comparison of the results of partial fixation with cement and fixation without any cement. AB - In a prospective, non-randomized study of 344 patients who had 392 primary total knee replacements with a Miller-Galante I prosthesis for the treatment of osteoarthrosis, the results of partial fixation with cement (insertion of the tibial and patellar components with cement and of the femoral component without cement) were compared with those of fixation without any cement. Of the 392 knees, 183 (163 patients) had fixation without cement (Group I) and 209 (181 patients), with and without cement (Group II). The average duration of follow-up was three years (range, two to five years). Nine patients died during the follow up period, but no others were lost to follow-up. Analysis of the knee scores, range of motion of the knee, radiographs, and rates of complications revealed no differences between the outcomes in the two groups during the follow-up period. The rate of complications due to problems related to the extensor mechanism was high in both groups: a reoperation was performed in fifteen (8 per cent) of the knees that had had fixation without cement and in nineteen (9 per cent) of those that had had both types of fixation. Thirteen patients had additional operative treatment for recurrent patellar dislocations; twelve patients, for abnormal wear of the polyethylene of the patellar component: two patients, for avulsion of the patellar ligament from the tibia; and two patients, for unexplained pain in the knee. In addition, there were eight patellar fractures (two of which led to a reoperation) and three deep infections (all of which led to a reoperation). PMID- 8444920 TI - Shoulder impingement syndrome: diagnosis, radiographic evaluation, and treatment with a modified Neer acromioplasty. AB - Seventy-one patients who had shoulder impingement syndrome were managed operatively with a modified Neer acromioplasty: thirty-seven, who had an intact rotator cuff, had a modified acromioplasty, and thirty-four, who had a torn cuff, had a modified acromioplasty and repair of the cuff. In the classic anterior acromioplasty as described by Neer, emphasis is placed on resection of the inferior prominence of the acromion. We believe that the removal of only the inferior prominence is insufficient, as often too much of the anterior aspect of the acromion protrudes beyond the anterior border of the clavicle. This portion of the acromion continues to irritate the subacromial bursa and the rotator cuff and to produce symptoms of impingement. Our modified acromioplasty is done in two steps: the portion of the acromion that projects anteriorly beyond the anterior border of the clavicle is resected vertically and then an anteroinferior acromioplasty is performed. We studied the results in patients who had been operated on by the senior one of us and who had been followed clinically for a minimum of two years. At the most recent follow-up visit, no difference in terms of pain and function was found between the patients who had had the modified acromioplasty only (Group I) and the patients who had had the modified acromioplasty and repair of the rotator cuff (Group II); thirty-three (89 per cent) of the patients in Group I and thirty (88 per cent) of those in Group II had a good or excellent result. PMID- 8444921 TI - Progression of a slipped capital femoral epiphysis after fixation with a single cannulated screw. A case report. PMID- 8444922 TI - Intraosseous infusion in infants. Case report of a complication. PMID- 8444923 TI - Compartment syndrome of the lower extremity after intraosseous infusion of fluid. A report of two cases. PMID- 8444924 TI - No time to vegetate. PMID- 8444925 TI - The diagnosis and orthopaedic treatment of inherited muscular diseases of childhood. PMID- 8444926 TI - Preparing manuscripts for publication in The Journal of Bone and Joint Surgery: responsibilities of authors and editors. A view from the editor of the American volume. PMID- 8444927 TI - Preparing manuscripts for publication in The Journal of Bone and Joint Surgery. A view from the former editor of the British volume. PMID- 8444928 TI - Fixation with a single screw for slipped capital femoral epiphysis. PMID- 8444930 TI - Tuberculosis of the spine. PMID- 8444929 TI - Massive femoral osteolysis and early disintegration of a polyethylene-bearing surface of a total knee replacement. A case report. PMID- 8444931 TI - Bone-marrow oedema syndrome. PMID- 8444932 TI - Fractures of the calcaneum. PMID- 8444933 TI - Survival analysis in joint replacement surgery. PMID- 8444934 TI - Intra-articular fractures of the calcaneum. Part I: Pathological anatomy and classification. AB - We have studied the radiographic and CT features of 120 displaced intra-articular fractures of the calcaneum in order to define the pathological anatomy. In 96% of cases, the CT scans identified three main fragments: sustentacular, lateral joint and body. The sustentacular fragment was often rotated into varus, the lateral joint fragment into valgus and the body fragment impacted upwards, in varus and displaced laterally. The displacement of these fragments varied according to which of three fracture types was present, as defined by the composition of the fractured lateral wall of the calcaneum. In type 1 it was formed by the lateral joint fragment alone; in type 2 by both body and lateral joint fragments; and in type 3 by the body fragment alone. Fracture fragment displacement differs from that previously described, in that true uniform depression of the lateral joint fragment is rare. PMID- 8444935 TI - Intra-articular fractures of the calcaneum. Part II: Open reduction and internal fixation by the extended lateral transcalcaneal approach. AB - The classification of intra-articular fractures of the calcaneum described in part I is related to an operative approach which allows accurate reduction and stable fixation of the fracture fragments. An extended lateral incision is used to avoid sural nerve damage and problems of soft-tissue healing. In type 3 fractures, access to the lateral joint fragment requires an osteotomy of the lateral wall, but after this the lateral joint fragment can be rotated out of the subtalar joint to allow transcalcaneal reduction of the medial wall. Reduction of the body fragment and lateral joint fragment on to the sustentacular fragment allows the three fragments to be stabilised by a 3.5 mm Y-shaped reconstruction plate. Our early results have been successful in terms of fracture reduction and the restoration of heel shape and joint congruity, but extended follow-up will be necessary to define the indications for this difficult procedure. PMID- 8444936 TI - Operative treatment of displaced intra-articular fractures of the calcaneum. Medium-term results. AB - Since 1986, we have treated displaced intra-articular fractures of the calcaneum by open reduction through a lateral approach, stable internal fixation and bone grafting. We assessed the results at a mean follow-up of 2.92 years in 44 patients, comparing them with those for 19 patients treated non-operatively. Clinical assessment used the scoring system of Crosby and Fitzgibbons (1990) and radiological measurements were made from lateral, axial and internal oblique views. The articular congruity of the subtalar joint and any arthritic changes were also assessed. We found significantly better results in the operated group with respect to pain, activity, range of movement, return to work and swelling of the hind foot. Radiologically, the operated group showed significantly better scores for articular congruity and arthritic changes. We conclude that the operative treatment of displaced intra-articular fractures of the calcaneum gives better medium-term results than conservative management. PMID- 8444937 TI - The effect of the entry hole for an intramedullary nail on the strength of the proximal femur. AB - We used 15 pairs of femora from fresh human cadavers to study the effects of the size and location of the entry hole for an intramedullary nail on the strength of the femur. Right femora were used as controls. Left femora in group 1 had a 10 mm entry hole in the 'ideal' location in the piriformis fossa. Group 2 had a 14 mm entry hole in the same position and group 3 had a 14 mm entry hole anterior to this on the superior aspect of the femoral neck. Femora were equipped with strain gauges and loaded to failure in compression. There was reduced stiffness and load to failure in group 3 specimens, suggesting that the location of the hole was more important than its size. PMID- 8444938 TI - Meniscal injury associated with femoral shaft fractures. An arthroscopic evaluation of incidence. AB - We studied 47 patients with closed, displaced, diaphyseal fractures of the femur caused by blunt trauma, to determine the incidence of associated knee injuries, particularly of the meniscus. After femoral nailing, all patients had an examination under anaesthesia and an arthroscopy. There were 12 medial meniscal injuries (5 tears) and 13 injuries of the lateral meniscus (8 tears). Ten of the 13 tears were in the posterior third of the meniscus, and two patients had tears of both menisci. Synovitis was common at the meniscal attachments. Complex and radial tears were more common than peripheral or bucket-handle tears. Examination under anaesthesia revealed ligamentous laxity in 23 patients (49%), but meniscal injuries had a similar incidence in knees with and without ligament injury. Femoral shaft fractures are often associated with injuries to the ipsilateral knee, and a high index of suspicion is necessary to identify these lesions. PMID- 8444939 TI - Bone-marrow oedema syndrome and transient osteoporosis of the hip. An MRI controlled study of treatment by core decompression. AB - Bone-marrow oedema syndrome (BMOS) of the hip gives a characteristic MRI pattern, in association with severe pain, non-specific focal loss of radiological density and a positive bone scan. In our MRI-controlled study, nine patients with non traumatic BMOS in ten hips all had core decompression. Bone-marrow pressure measurements and intraosseous venography in five cases showed pathological values. All patients had immediate relief of pain, with return of MRI signals to normal after three months. Regular review was continued for at least 24 months with serial clinical radiological and MRI assessment. At a mean follow-up of 33 months all patients remained free of pain with normal radiographs and MR scans. The histological evaluation of undecalcified sections obtained from eight core decompressions confirmed the presence of bone-marrow oedema, with necrotic and reparative processes involving bone and marrow similar to those of early avascular necrosis but with no evidence of 'osteoporosis'. These findings support the assumption that BMOS may be the initial phase of non-traumatic avascular necrosis. In most patients BMOS will have a self-limiting course, but the duration of symptoms may be reduced by core decompression treatment. PMID- 8444940 TI - Avascular necrosis of the femoral head. Natural history and magnetic resonance imaging. AB - We studied the prognostic value of MRI in 32 radiographically normal, asymptomatic hips in 25 patients at risk of osteonecrosis from glucocorticoids or alcoholism. The early findings were band-like hypointense zones on spin-echo images. No operations were performed. Life-table survival curves showed that femoral heads in which the hypointense zone traversed the middle portion of the head were most at risk of subsequent segmental collapse. PMID- 8444941 TI - Dome osteotomy of the pelvis for osteoarthritis secondary to hip dysplasia. An over five-year follow-up study. AB - We performed Kawamura's dome osteotomy of the pelvis, with simultaneous distal transfer of the greater trochanter on 101 hips in 91 patients with osteoarthritis secondary to hip dysplasia. The mean age at operation was 30 years (15 to 55), and follow-up was for a mean of 8.3 years (5 to 14). Clinical evaluation using the Merle d'Aubigne score showed 92% excellent or good results. Radiologically, 91 hips had good acetabular remodelling and showed no signs of progression of osteoarthritis. In ten hips the osteoarthritic process progressed despite the osteotomy and six of these eventually underwent total hip replacement. Factors which were significantly associated with a poor outcome included an advanced stage of osteoarthritis, valgus deformity of the proximal femur, old age at the time of operation and postoperative persistence of abductor insufficiency. PMID- 8444942 TI - The definition and measurement of acetabular orientation. AB - The orientation of an acetabulum or an acetabular prosthesis may be described by its inclination and anteversion. Orientation can be assessed anatomically, radiographically, and by direct observation at operation. The angles of inclination and anteversion determined by these three methods differ because they have different spatial arrangements. There are therefore three distinct definitions of inclination and anteversion. This paper analyses the differences between the definitions and provides nomograms to convert from one to another. It is recommended that the operative definitions be used to describe the orientation of prostheses and that the anatomical definitions be used for dysplastic acetabula. PMID- 8444943 TI - Imaging in children with spinal tuberculosis. A comparison of radiography, computed tomography and magnetic resonance imaging. AB - We compared the usefulness of radiography, CT and MRI in 25 children with spinal tuberculosis. Radiography provided most of the information necessary for diagnosis and treatment. Axial CT was the most accurate method for visualising the posterior bony elements. Sagittal MRI best showed the severity and content of extradural compression and helped to differentiate between an abscess and fibrous tissue. The main value of CT and MRI is in the preoperative evaluation of the small proportion of patients who require surgical treatment for paraplegia. PMID- 8444944 TI - Controlled trial of short-course regimens of chemotherapy in the ambulatory treatment of spinal tuberculosis. Results at three years of a study in Korea. Twelfth report of the Medical Research Council Working Party on Tuberculosis of the Spine. AB - After exclusions, 265 patients with tuberculosis of the thoracic and/or lumbar spine were followed for three years from the start of treatment. They were randomly allocated to four daily regimens of chemotherapy: 1) isoniazid plus rifampicin for 6 months (6HR, 65); 2) the same drugs as in 1) but for 9 months (9HR, 71); 3) isoniazid plus paraaminosalicylic acid (PAS) or ethambutol for 9 months (9P/EH, 62); or 4) the same drugs as in 3) but for 18 months (18P/EH, 67). All patients were ambulatory from the start of chemotherapy and no form of splintage or support or operation was used in any case. Over half (55%) the patients were children and one-third had sinuses or clinically evident abscesses. At three years a favourable status, defined as no sinus nor clinically evident abscess, no myelopathy with functional impairment, no surgery nor additional chemotherapy, full physical activity with disease quiescent clinically and radiographically, was achieved in 203 patients (77%) and in another 41 (15%) in all respects except radiographically. Only 20 patients (8%) had an unfavourable status the proportion being highest (19%) in the 9P/EH series. Thirteen of these were classified as unfavourable solely because they had needed additional chemotherapy; only seven still had an unfavourable status at three years. The clinical results at three years were thus excellent in all series except the 9P/EH, in which more patients had required additional chemotherapy. In the 88 patients with sinuses or abscesses on admission, the rate of resolution was similar in all the series; most lesions (83%) had resolved by 12 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444945 TI - Polyethylene wear in cemented metal-backed acetabular cups. AB - We examined radiographic polyethylene wear in 233 cemented total hip arthroplasties (201 patients) with either a metal-backed or a non-metal-backed acetabular cup. All patients had identical cemented one-piece titanium femoral stems with a femoral head diameter of 28 mm. The mean linear wear rate was 0.11 mm/yr in metal-backed sockets and 0.08 mm/yr in non-metal-backed sockets (p = 0.0002). The mean volumetric wear rate was 66.2 mm3/yr in the metal-backed sockets and 48.2 mm3/yr in the polyethylene sockets (p = 0.0002). The addition of metal backing to a cemented acetabular cup therefore resulted in a 37% increase in mean polyethylene wear rates which may partially explain the higher failure rate of cemented metal-backed cups. Linear regression analysis also implicated increased follow-up time (log), gross acetabular migration, metal backing and male gender in increasing polyethylene wear. We advocate the use of an all polyethylene cup in cemented total hip arthroplasty. The increased polyethylene wear must also cause concern about the wear rate of uncemented metal-backed acetabular sockets. PMID- 8444946 TI - In vivo wear of polyethylene acetabular components. AB - Polyethylene acetabular cups retrieved at revision surgery were measured by a shadowgraph technique to determine linear wear, and the values were compared with those obtained from radiographs. There was a close correlation between them, although the radiographic measurements slightly underestimated the true wear. Average linear wear rates for surface-replacement components were much greater than those for conventional prostheses with femoral heads up to 32 mm in diameter. Volumetric wear, calculated using a new formula, was found to be less than previously reported in vivo, and similar in magnitude to the results of experimental wear tests in vitro. The volumetric wear rates were greatest for the surface-replacement components and, for conventional components, were found to increase in a linear manner with component diameter. PMID- 8444947 TI - Fracture and loosening of Charnley femoral stems. Comparison between first generation and subsequent designs. AB - We report the results of a 4- to 17-year clinical and radiological follow-up of 264 Charnley first-generation stems in comparison with those of 402 second- and subsequent-generation stems. The incidence of fracture was 4.1% in first generation stems and 0.5% in second- and subsequent-generation stems. The incidence of stem loosening requiring or likely to require revision was 3.1% in first-generation and 11.4% in second-generation stems. We believe that the increased loosening rate in second- and subsequent-generation stems is due to their larger cross-sectional area, which produces an increase in flexural stiffness. PMID- 8444948 TI - Inguinal lymphadenopathy due to metal release from a prosthesis. A case report. AB - We report the case of a 19-year-old man with inguinal lymphadenopathy caused by metallic debris from the loosening of a prosthesis inserted after tumour resection. Large amounts of wear debris may be released from such massive replacements, and surgeons should be aware of the range of possible adverse effects. PMID- 8444949 TI - Hydroxyapatite coating converts fibrous tissue to bone around loaded implants. AB - In previous studies, we have demonstrated a fibrocartilaginous membrane around hydroxyapatite-coated implants subjected to micromovement in contrast to the fibrous connective tissue which predominates around similarly loaded titanium alloy implants. In the present study, in mature dogs, we investigated the effect of immobilising titanium (Ti)- or hydroxyapatite (HA)-coated implants already surrounded by a movement-induced fibrous membrane and compared the results with those of similar implants in which continuous micromovement was allowed to continue. The implants were inserted in the medial femoral condyles of 14 dogs and subjected to 150 microns movements during each gait cycle. After four weeks (when a fibrous membrane had developed), half the implants were immobilised to prevent further micromovement. The dogs were killed at 16 weeks and the results were evaluated by push-out tests and histological analysis. The continuously loaded Ti-coated implants were surrounded by a fibrous membrane, whereas bridges of new bone anchored the HA-coated implants. The immobilised implants were surrounded by bone irrespective of the type of coating. Push-out tests of the continuously loaded implants showed better fixation of those with HA coating (p < 0.001). The immobilised Ti-coated implants had four times stronger fixation than did continuously loaded Ti-coated implants (p < 0.01) but there was no equivalent difference between the two groups of HA-coated implants. The amount of bone ingrowth was greater into immobilised HA-coated implants than into immobilised Ti coated implants (p < 0.01). Two-thirds of the HA coating had been resorbed after 16 weeks of implantation, but 25% of this resorbed HA had been replaced by bone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8444950 TI - Dual-energy X-ray absorptiometry measurement of bone mineral density around porous-coated cementless femoral implants. Methods and preliminary results. AB - The measurement of bone mineral density in defined areas around metal implants has improved with the development of dual-energy X-ray absorptiometry. We used this technique to compare the bone mineral density adjacent to metal cementless femoral implants with that of identical regions of bone in normal proximal femora. We studied the anteroposterior views only of 72 femora which contained total hip implants and 34 non-operated femora. We compared the regional bone mineral density of bone adjacent to proximally porous-coated and distally porous coated implants of one design, to measure the relative differences in the remodelling changes induced by different amounts of porous coating. We also measured differences in bone density with time and with variations in implant size (and therefore stiffness). The greatest decrease in bone mineral density (34.8%) occurred in the most proximal 1 cm of the medial femoral cortex around relatively stiff, extensively porous-coated implants. The next most severe decrease (20% to 25%) was in the next most proximal 6 cm of the medial femoral cortex. Small, progressive decreases in bone mineral density continued for five to seven years after implantation. PMID- 8444951 TI - Plasma bone-specific alkaline phosphatase as an indicator of osteoblastic activity. AB - The total plasma alkaline phosphatase level has long been recognised as an indicator of osteoblastic activity, but lack of specificity makes it an insensitive index of the progress of disease and the response to treatment. Selective precipitation by wheatgerm lectin allows measurement of the plasma bone specific alkaline phosphatase. We measured the plasma levels of this isoenzyme in 170 normal Chinese adolescents and adults, in 49 adults with fractures of a long bone, in 15 patients with osteosarcoma and in 38 patients with osteolytic metastases. The enzyme activity was also determined in 39 patients with liver disease. Of the patients with fractures, 94% had increased plasma activity during the healing process. The level was also increased in those with osteosarcoma but not in those with osteolytic bone metastases. There was no significant increase in activity in the patients with liver disease. We conclude that the plasma bone specific alkaline phosphatase activity is a sensitive and reliable measure of osteoblastic activity. PMID- 8444952 TI - Cysts of the medial meniscus. Arthroscopic diagnosis and management. AB - We report the clinical and arthroscopic findings in 20 cases of medial meniscal cyst with a mean follow-up of 20 months. These were studied prospectively from a series of 7435 knee arthroscopies in which there were 1246 stable non-arthritic knees with medial meniscal tears. The diagnosis on referral was incorrect in seven, and incomplete in seven. There was coexistent meniscal injury in 17 (85%), but in the other three no tear was visible at arthroscopy. Ten knees had additional intra-articular abnormalities. Treatment of the cyst was by open resection in 12 and arthroscopic evaluation at meniscectomy in seven. In one case the cyst resolved after arthroscopic partial meniscectomy alone. Meniscal tears were treated by arthroscopic partial medial meniscectomy. Medial meniscal cysts are an important but under-diagnosed cause of knee pain and are frequently related to arthroscopically diagnosable and treatable meniscal pathology. Treatment should be directed towards both the meniscus and the cyst, which may require open surgery. PMID- 8444953 TI - Arthroscopic treatment of cysts of the lateral meniscus. AB - We have treated 69 patients with 72 cystic lateral menisci by arthroscopic surgery. Meniscal tears were observed in all cases, and 69 of these had a horizontal cleavage component. Three types of tear were identified and may be progressive. Treatment was by arthroscopic resection of the meniscal tear, and decompression of the cyst through the substance of the meniscus. After a mean follow-up of 34 months the results were good or excellent in 64 knees (89%) and there were few complications. We recommend this technique as the treatment of choice for cysts of the lateral meniscus. PMID- 8444954 TI - Arthroscopic treatment of meniscal cysts. AB - In a series of 1160 arthroscopies we found 16 meniscal cysts; 12 involved the lateral joint line and two the medial, and two were intra-articular. In all but two cases, arthroscopy showed meniscal tears. We recommend arthroscopy of all cases to correct the meniscal lesion, and to evacuate the cyst into the joint by opening the joint capsule. This was successful in 12 cases, with no recurrence after an average follow-up of 18 months. Only two patients with no meniscal lesion on arthroscopy required an additional external incision for cyst removal. PMID- 8444955 TI - Pes anserinus transposition for patellar dislocations. Long-term follow-up results. AB - Transposition of part of the pes anserinus was used to treat 96 knees in 78 patients with recurrent, habitual or permanent dislocations of the patella. The knees with habitual (48) and permanent (27) dislocations also had extensive release of superolateral contracture. The patients were reviewed at an average follow-up of 9 years 8 months. The medial stability of the patella had been improved in all the cases. There were no recurrences in 21 knees with recurrent dislocations. There were four recurrences (5.3%) in knees with habitual and permanent dislocations due to inadequate release of the superolateral contracture and incorrect transfer of the whole of the pes anserinus. Correction of these technical errors prevented further recurrence in all four cases. PMID- 8444956 TI - Proprioception after rupture of the anterior cruciate ligament. An objective indication of the need for surgery? AB - Failure of conservative treatment is the usual indication for the reconstruction of a knee with deficiency of the anterior cruciate ligament (ACL) and this depends on subjective judgement. The ability of muscles to protect the subluxing joint by reflex contraction could provide an objective measurement. We have studied 30 patients with unilateral ACL deficiency by measuring the latency of reflex hamstring contraction. We found that the mean latency in the injured leg was nearly twice that in the unaffected limb (99 ms and 53 ms respectively). There was a significant correlation between the differential latency and the frequency of 'giving way' indicating that functional instability may be due, in part, to loss of proprioception. Measures of proprioception, including reflex hamstring latency, may be useful in providing an objective assessment of the efficacy of conservative treatment and the need for surgery. PMID- 8444957 TI - Ruptured Baker's cyst causes ecchymosis of the foot. A differential clinical sign. AB - Three consecutive patients with ruptured Baker's cysts, verified by duplex scan, were found to have ecchymosis on the dorsum of the foot. The appearance of ecchymosis can be helpful in differentiating a ruptured cyst from cellulitis or deep-vein thrombosis. PMID- 8444958 TI - Septic arthritis of the shoulder after mastectomy and radiotherapy for breast carcinoma. AB - We report five patients who developed septic arthritis of the shoulder after cancer of the ipsilateral breast had been treated by surgery and radiotherapy. Lymphoedema was present in all cases. The infections were not obvious, having subacute onsets, and delays in diagnosis led to destruction of the joint in all but one patient. PMID- 8444959 TI - Treatment of ulnar nerve palsy at the elbow with a night splint. AB - Twenty-two patients with ulnar nerve palsy at the elbow, confirmed by electromyography, were treated by a night splint which prevented flexion of the elbow beyond 60 degrees. The splint was worn all night regularly for at least six months. At a mean follow-up of 11.3 months, 17 patients had clinical and electromyographic assessment and five were contacted by telephone. There was improvement in the symptoms in every patient, including three who had failed to respond to surgical decompression. There was electromyographic improvement in 16 of the 17 patients re-examined at follow-up. The mean improvement in motor nerve conduction velocity was 6.5 m/s and in sensory nerve conduction velocity 9.5 m/s. The efficacy of this treatment suggests that nocturnal elbow flexion is an important cause of ulnar nerve lesions at the elbow. PMID- 8444960 TI - Reduction of posterior dislocation of the hip in the prone position. PMID- 8444961 TI - Bilateral dislocation of the proximal humeral epiphyses in septic arthritis: a case report. PMID- 8444962 TI - A composite bone flap to lengthen a below-knee amputation stump. PMID- 8444963 TI - The subcapsular approach for lesions of the femoral neck. PMID- 8444964 TI - MRI of the intervertebral disc. PMID- 8444965 TI - Acetabular fracture lines. PMID- 8444967 TI - Nerve used as tendon graft. PMID- 8444966 TI - Missed Monteggia fracture. PMID- 8444968 TI - The pathology of upper-extremity arterial disease. AB - The arteries to the upper extremities can be involved at multiple levels by a variety of diseases. Because of the critical sensitivity of motor function and sensation in the arms and hands, minor degrees of ischemia can have major clinical significance. It is essential to understand the exact pathologic process and the sites of involvement to provide proper therapy. PMID- 8444970 TI - Pulse volume recording. AB - Noninvasive studies, in general, and pulse volume recordings (PVRs), in particular, play important roles in diagnosis, planning, and monitoring of therapy for vascular disorders of the upper extremity. Essentially, PVR is a useful screening tool to show whether hemodynamically significant vascular disease has produced alterations of digital flow patterns. PVR also has a role in differentiating between vasospastic and vaso-occlusive disease, in evaluating cold sensitivity, in monitoring medical and surgical treatments, and as a research tool. This method also has its limitations, which must be appreciated, to place the true role of this very useful noninvasive modality in proper perspective. PMID- 8444969 TI - Acute vascular injuries of the upper extremity. AB - Heightened awareness of the pathologic conditions resulting in acute vascular trauma will govern the success of management. A thorough examination with appropriate vascular studies followed by meticulous surgical intervention and a carefully monitored postoperative course avoids the associated complications of these challenging injuries. PMID- 8444971 TI - Vascular compression about the shoulder. AB - Arterial and venous compression about the shoulder girdle are rare clinical entities. Potential complications can be disastrous for the patient. A heightened awareness of the problem and careful physical examination may lead to earlier diagnosis. Controversy still exists as to the optimal treatment once diagnosis is confirmed. Evolution of noninvasive diagnostic techniques may be of considerable benefit in the future. PMID- 8444972 TI - Occlusive vascular disorders of the upper extremity. AB - Arterial occlusive disease of the upper extremity is most often due to posttraumatic occlusion of the ulnar artery. An embolic source of the ischemia should be considered most strongly when sudden ischemia or vasospasm is associated with atrial fibrillation or follows a myocardial infarction. Connective tissue disorders and several arteridities are infrequent causes of upper-extremity occlusive disease and can usually be detected by a thorough peripheral vascular examination and blood studies. Atherosclerosis of the upper extremity is usually localized to the region of the subclavian artery and can present as a subclavian steal syndrome or arm ischemia. Finally, upper-extremity venous occlusive disease occurs in association with the hypercoagulable state, venous endothelial injury, or arises in otherwise healthy patients because of venous impingement in the thoracic outlet. PMID- 8444973 TI - Vasospastic disorders. Etiology, recognition, and treatment. AB - This article discusses a group of disorders commonly unappreciated by physicians. The distinction between Raynaud's disease and Raynaud's phenomenon is reviewed. The classification, pathophysiology, and recognition of the vasospastic diseases is reviewed to lay the foundation for understanding the treatment modalities presented. PMID- 8444974 TI - Color duplex imaging. Applications to upper-extremity and microvascular surgery. AB - Color duplex scanning is a relatively new noninvasive vascular test combining ultrasound, Doppler recording, and color. It has numerous documented applications to various other subspecialties but only recently has been used in upper extremity and microvascular surgery. It is quite useful in evaluating masses, perfusion abnormalities, trauma, and aberrant or repaired vasculature in the upper extremity. Applications to rotational and free tissue transfers include preoperative evaluation of both the donor and recipient vessels as well as postoperative monitoring. PMID- 8444975 TI - The examination in the vascular laboratory. AB - Using the examination of any body system, and examiner must be able to detect and assess disease as accurately as possible and then evaluate the status of the remaining function. When studying the vascular system of the upper extremity in particular, physiologic information must be provided in addition to the more commonly investigated structural information. The circulatory system fluctuates to meet the stresses of everyday life. Critical functional data can be provided by a knowledgeable technician in a vascular laboratory with a variety of noninvasive techniques and testing approaches. Not only can the presence and location of vascular disease be determined, but also the subsequent medical or surgical treatment can be facilitated. Even more important, standardized testing protocols can be adapted to fit the individual needs of a patient. PMID- 8444976 TI - Stress testing in the evaluation of upper-extremity perfusion. AB - Stress testing is an important element in the evaluation of upper extremity vascular perfusion. Advances in noninvasive testing provide mechanisms to evaluate the static structural characteristics of the arterial system, to define patient and nonpatient vessels to identify areas of thrombosis or occlusion, to evaluate arterial wall motility and elasticity, and to observe the nutritional capillary bed. To understand upper-extremity vascular function, however, some form of stress testing is crucial. The techniques discussed previously continue to evolve and serve only as examples of the potential of noninvasive tests evaluated before, during, and after stress. Stress testing provides techniques that allow us to understand the functional components of vascular perfusion and to monitor our attempts at interventions. PMID- 8444977 TI - Nuclear medicine, contrast angiography, and magnetic resonance imaging for evaluating vascular problems in the hand. AB - Techniques for imaging the vascular tree have undergone change and development. Nuclear imaging can lead to decisions concerning diagnoses of masses, while contrast angiography with digital subtraction gives a complete picture of the vessels. Magnetic resonance angiography is the most exciting advance. Completely noninvasive, it yields much the same information as conventional contrast angiography. PMID- 8444978 TI - Seizure in a five-year-old. PMID- 8444979 TI - Lambert-Eaton syndrome. PMID- 8444980 TI - Diabetic nephropathy: a comprehensive approach. AB - By the time the traditional dipstick test shows excess urinary albumin, glomerular damage may be beyond repair and nephrotic syndrome virtually guaranteed. More sensitive assays provide earlier warning, allowing the clinician to institute a surveillance and antihypertensive program that--along with dietary glycemic control--can stave off disease progression. PMID- 8444981 TI - The evaluation of comatose patients. PMID- 8444982 TI - Mental calisthenics. PMID- 8444983 TI - Tachycardia, shock, and pulmonary edema. PMID- 8444984 TI - Swelling in two patients with lupus. PMID- 8444986 TI - Policy challenges and clinical practices. PMID- 8444985 TI - Targeted hormone therapy for breast cancer. AB - Large-scale studies now provide relatively clear guidelines for the clinician on antiestrogen treatment in various patient populations and subgroups. Future challenges are to determine whether antiestrogens might be used for prevention, to identify the environmental and genetic causes of breast cancer, and to develop new approaches to this tumor, such as antiprogestins. PMID- 8444987 TI - Children's reactions to traumatic events. PMID- 8444988 TI - One-year outcomes of depressive disorders in child psychiatric in-patients: evaluation of the prognostic power of a brief measure of expressed emotion. AB - The association between 1-year post-hospitalization outcome and the brief Five Minute Speech Sample (FMSS) measure of expressed emotion (EE) was examined among children with depressive disorders. Results indicated a strong association between 1-year outcome and the FMSS-EE measure. Whereas children returning to high EE homes were likely to show persistent mood disorder, recovery was more common among children returning to low EE homes. This predictive relationship was independent of possible mediating variables such as treatment regimen and clinical characteristics. Results provide the first reported demonstration that (1) the brief FMSS-EE measure predicts clinical outcome, and (2) EE measures predict 1-year outcome for children with depressive disorders. PMID- 8444989 TI - Diagnostic specificity of a brief measure of expressed emotion: a community study of children. AB - The association between expressed emotion (EE) and psychiatric disorders was investigated in a community survey of 108 preadolescent children. Results indicated that the two components of EE, critical comments and emotional overinvolvement, identified non-overlapping subsets of families and displayed diagnostic specificity. Significantly higher rates of disruptive behavior diagnoses were observed in children of parents who expressed high levels of criticism, while children of parents who expressed high levels of emotional overinvolvement were significantly more likely to have an anxiety disorder when compared to the remaining sample. Findings support the utility of this brief measure of EE in epidemiologic samples. PMID- 8444990 TI - The effect of family counselling on the mental health of 10-11-year-old children in low- and high-risk families: a longitudinal approach. AB - This study investigated the effect of family counselling on the child's mental health in low- and high-risk families. The material consisted of 160 families with a baby born in 1975-76. First, the families were classified with a weighted risk index into low- and high-risk families. Eighty of the families attended a five-year-long family counselling program. The results of a ten year follow-up study showed that both the initial family risk and the counselling made a statistically significant contribution to the 10-11-year-old child's mental health. The counselling had a positive effect both in low- and high-risk families. PMID- 8444991 TI - Risk and resistance factors in the adaptation of parents of children with severe physical disability. AB - Associations between descriptor variables of child characteristics, life events, parental resources and coping strategies and outcome measures of psychological distress, satisfaction with life and adaptation to the child were investigated for both mothers and fathers in a sample of families of children with severe physical disability. Results indicated high levels of psychological distress, particularly for mothers. Personality factors, coping strategies, life events and socio-economic disadvantage were related to outcome for both parents. For mothers, greater physical disability and communication problems in the child were risk factors; for fathers, child gender and feeding problems showed significant associations with outcome. PMID- 8444992 TI - Evaluation of the revised Ontario Child Health Study scales. AB - This article describes the development and evaluation of the revised Ontario Child Health Study (OCHS) scales to measure conduct disorder, oppositional disorder, attention-deficit hyperactivity disorder, overanxious disorder, separation anxiety and depression based on DSM-III-R symptom criteria. Problem checklist assessments were obtained from parents and teachers of children aged 6 16 and youths aged 12-16 drawn from: (1) a general population sample (N = 1751); and (2) a mental health clinic sample (N = 1027) in the same industrialized, urban setting. Evaluation of the revised OCHS scales indicates that they possess adequate psychometric properties and provide an efficient means to obtain measurements of childhood psychiatric disorder, in general population studies, that correspond to DSM-III-R classification of disorder. PMID- 8444993 TI - Early dentine lead levels and subsequent cognitive and behavioural development. AB - While a number of studies have reported associations between lead levels and cognitive development and behaviour in cross-sectionally studied child samples, there have been relatively few studies of the long term effects of early lead exposure. This issue was studied in a birth cohort of 1265 New Zealand children who were assessed with respect to: (a) dentine lead levels at ages 6-8 years; (b) cognitive and behavioural outcomes at 12, 13 years; (c) various confounding factors. The results of the analysis show: (a) the presence of small but consistent bivariate associations (ranging in absolute size from r = .08 to .20) between early lead levels and later school performance and behaviour; (b) after adjustment for both errors of measurement in test scores and lead levels and adjustment for confounding factors these correlations reduced to between .07 and .14. Nonetheless these correlations remained statistically significant. The evidence is consistent with the view that early mildly elevated lead levels are associated with small but relatively long term deficits in cognitive ability and attentional behaviours. PMID- 8444994 TI - Distinct periods of mother-infant conflict in normal development: sources of progress and germs of pathology. AB - Questionnaire and interview data were collected on 15 mothers with babies between 0 and 20 months old. A prospective, longitudinal design was used. Mother-infant conflicts were clustered in distinct, difficult periods and were preceded by regressive behaviour of the infant. It is argued that conflict creates opportunities for learning and progress. On the other hand, it is discussed how mother-infant conflict can escalate into abuse, neglect and psychopathology. PMID- 8444995 TI - Causal attributions and post-traumatic stress in adolescents. AB - The aim of the present study was to explore the relationship between causal attributions made by adolescent survivors of the Jupiter cruise ship sinking, and post-traumatic symptomatology in the year following disaster. Evidence is presented that more internal causal attributions for negative and uncontrollable events during the incident are associated with greater post-traumatic stress one year later. The findings are discussed with reference to an attributional model of shame. PMID- 8444996 TI - Handedness distribution and figure drawing ability in a deaf school population, with severe learning difficulties: a research note. AB - The handedness distribution of 71 deaf pupils with severe learning difficulties, was found to be similar to that reported by Soper et al. (1987, American Journal of Mental Deficiency, 92, 94-102) in a mentally handicapped sample, who also found a high incidence of ambiguously handed individuals. Soper's theory, however, that the "acquired" left-handed and the ambiguously-handed are more handicapped and so, we might infer, draw more primitive human figures, was not supported. The left, ambiguously-handed and right-handed had the same scores on human figure drawing. Neither was there a difference in handedness or figure drawing between the "acquired", the "genetic" and the "unknown" cause groups; nor between males and females. PMID- 8444997 TI - Separation of glucooligosaccharides and polysaccharide hydrolysates by gradient elution hydrophilic interaction chromatography with pulsed amperometric detection. AB - Commercial glucooligosaccharide mixtures (Polycose) and polysaccharide hydrolysates (acid and enzymatic) were fractionated by hydrophilic interaction chromatography and observed by pulsed amperometric detection. Seven peaks were observed when 625 ng of glucose oligomers in Polycose were fractionated. The between-run precision of retention times (n = 10, 100 micrograms, 15 peaks) ranged from a relative standard deviation (R.S.D.) of 0.09 to 0.40%; between-run precision of peak areas (n = 10) for the same separations had values that ranged from 2.66 to 14.4%. Injection-to-injection time was 48 min. When polysaccharide hydrolysates were fractionated using a gradient program capable of resolving all of the oligosaccharide species, dextran-derived alpha-(1-->6) glucooligosaccharides were retained to a greater degree than amylose-derived alpha-(1-->4)-glucooligosaccharides, which were retained to a greater degree than beta-(2-->1)-fructooligosaccharides derived from inulin. Excluding the peaks that eluted before glucose or fructose, 25 to 35 peaks were observed after fractionation of the hydrolysates. Differences in elution profiles were observed between acid and enzymatic hydrolysis products of the same polysaccharide as well as between hydrolysis products of different polysaccharides. In conjunction with high-performance size-exclusion chromatography, the method demonstrated the effect of preheating starch before hydrolysis with isoamylase. PMID- 8444998 TI - Determination of hyaluronic acid by high-performance liquid chromatography of the oligosaccharides derived therefrom as 1-(4-methoxy)phenyl-3-methyl-5-pyrazolone derivatives. AB - Hyaluronic acid (HA) was digested with various kinds of depolymerizing enzymes and the products were analysed by high-performance liquid chromatography (HPLC) after derivatization with 1-(4-methoxy)phenyl-3-methyl-5-pyrazolone (PMPMP). As hyaluronate 4-glycanohydrolase (EC 3.2.1.35) from sheep testis showed a high efficiency for depolymerization, giving the tetra- and hexasaccharides abundantly, and is inexpensive, a method for the specific determination of HA was established, based on digestion by this enzyme followed by determination of the tetra- or hexasaccharide derived therefrom as the PMPMP derivatives by HPLC with UV detection. This method allowed the determination of HA in the range 0.5-50 micrograms with high reproducibility. PMID- 8444999 TI - Separation and isolation of trace impurities in L-tryptophan by high-performance liquid chromatography. AB - A high-performance liquid chromatographic (HPLC) profiling method was developed to separate trace impurities in L-tryptophan products associated with the eosinophilia-myalgia syndrome (EMS) epidemic. The test portion was dissolved in water, and the solution was filtered and chromatographed on a silica-based C18 reversed-phase HPLC column by using linear gradient elution with water and acetonitrile-water (80:20); both solvents contained 0.1% trifluoroacetic acid for ion-pairing. The method was used to profile 200 test samples from six manufacturers of L-tryptophan. The method was modified to include the use of a C18 disposable cartridge to retain the 1,1'-ethylidene-bis(L-tryptophan) (peak E, peak 97 or EBT), the impurity most strongly associated with EMS, and to remove the L-tryptophan before HPLC separation and quantitation. Recoveries of EBT added to test portions (2 micrograms/g and above) averaged 80%. PMID- 8445000 TI - Quantitative analysis of tylosin by column liquid chromatography. AB - A column liquid chromatographic method suitable for the quality control of tylosin A is described. The determination can be carried out on different C8 or C18 columns, using a mobile phase containing acetonitrile, 0.2 M tetrabutylammonium hydrogensulphate, 0.2 M phosphoric acid and water. The flow rate is 1 ml/min and detection is performed at 280 nm. The method shows good selectivity towards the major components tylosin A, B, C and D and demycinosyltylosin. Minor degradation products, mainly observed in solutions, are also separated. The compositions of several standards are compared and results for a number of commercial samples are presented. PMID- 8445001 TI - Simultaneous determination of planar chlorobiphenyls and polychlorinated dibenzo p-dioxins and -furans in Dutch milk using isotope dilution and gas chromatography high-resolution mass spectrometry. AB - A method is described for the simultaneous determination of planar chlorobiphenyls and dioxins in milk using isotope dilution and gas chromatography high-resolution mass spectrometry (GC-MS). The method is based on gel permeation chromatography, alumina clean-up and carbon chromatography and is highly automated, making a high sample throughput possible. Data on recovery, accuracy and reproducibility of results obtained with quality control samples are presented. Data for both dioxins and planar chlorobiphenyls from the analysis of samples of Dutch milk from several areas in the Netherlands are also presented. Possible interference of the chlorobiphenyls in the determination of the dioxins in the GC-MS method is discussed. PMID- 8445002 TI - Protein and peptide mobility in capillary zone electrophoresis. A comparison of existing models and further analysis. AB - Capillary zone electrophoresis of peptide fragments from the tryptic digest of human recombinant insulin-like growth factor I (rhIGF-I) has been carried out and the observed mobilities used to compare the relative applicability of existing mobility models. In addition, the physical forces affecting electromigration have been systematically analyzed in order to more accurately describe the physical chemistry involved. Such an approach should further improve the ability to predict electrophoretic mobility in capillary zone electrophoresis. PMID- 8445003 TI - Determination of the number and relative molecular mass of subunits in an oligomeric protein by two-dimensional electrophoresis. Application to the subunit structure analysis of rat liver amidophosphoribosyltransferase. AB - To determine simultaneously the relative molecular mass (M(r)) of a native oligomeric protein, and the number and M(r) of its subunits, a method using two dimensional electrophoresis was developed. To determine the M(r) of a native oligomeric protein, pore gradient gel electrophoresis was performed for the first dimension. Native proteins were dissociated into their subunits by sodium dodecyl sulphate (SDS) in a gel slice, then applied to SDS polyacrylamide gel electrophoresis for the second dimension to determine the M(r) of subunits. The advantage, accuracy, limitations and application of the method are discussed. PMID- 8445004 TI - Glycosaminoglycans and proteins: different behaviours in high-performance size exclusion chromatography. AB - The influence of the conformation of globular proteins and glycosaminoglycans in high-performance size-exclusion chromatography (HPSEC) was studied. Glycosaminoglycans (heparin, chondroitin sulphate and dermatan sulphate) with different primary structures, sulphate-to-carboxyl ratios and physico-chemical properties were extracted and purified. Their physico-chemical properties and purity were evaluated by several analytical techniques. Glycosaminoglycans with different relative molecular masses (M(r)) were prepared by a chemical depolymerization process. These heteropolysaccharides were evaluated by HPSEC and compared with globular proteins of known relative molecular mass. The two third degree polynomial regression curves for proteins and glycosaminoglycans have different coefficients and the columns present different exclusion limits. In particular, under the experimental conditions, the M(r) exclusion limits for high M(r) are 44,000 for glycosaminoglycans and 240,000 for globular proteins. In contrast, the behaviours of these two classes of macromolecules are similar for lower M(r). In fact, the two third-degree polynomial curves show the same regression below about M(r) = 1000. The behaviour in HPSEC is discussed in relation to the different steric conformations for proteins and glycosaminoglycans with different relative molecular masses. PMID- 8445005 TI - High-performance liquid chromatographic determination of cardenolides in Digitalis leaves after solid-phase extraction. AB - For HPLC analysis of cardenolide glycosides of Digitalis lanata the separation of the main compounds from other constituents is useful. An improved method for doing this, based on solid-phase extraction on a C18 modified poly(styrene divinylbenzene) polymer, is described. The presented assay permits quantitative estimation of more than 50 cardenolides in about 2 mg of dried leaf powder of Digitalis lanata with high speed and accuracy. PMID- 8445006 TI - Determination of acidic saponins in crude drugs by high-performance liquid chromatography on octadecylsilyl porous glass. AB - High-performance liquid chromatographic (HPLC) analysis on octadecylsilyl porous glass was investigated for acidic saponins in ginseng, bupleurum root and senega. The acidic saponins, malonyl-ginsenosides, malonyl-saikosaponins and senegins, as well as neutral saponins in the crude drugs were separated rapidly by HPLC on this column with aqueous acetonitrile containing KH2PO4 as the mobile phase at room temperature. PMID- 8445007 TI - Clinical review 43: Treatment of hypertension: focus on prevention of coronary heart disease. PMID- 8445008 TI - Insulin and blood pressure: fact or fantasy? PMID- 8445009 TI - An epidemiological test of the hyperinsulinemia-hypertension hypothesis. AB - The association between hyperinsulinemia and hypertension was tested in a population of 421 men and 228 women from the Baltimore Longitudinal Study of Aging. Subjects are white, middle-class, generally healthy, community-dwelling volunteers who ranged in age from 17-95 yr. Those with disease or medications known to influence any of the studied variables were excluded from the analysis. Twenty-five percent of the subjects were borderline or hypertensive [systolic blood pressure (BP) > or = 140 or diastolic BP > or = 90 mm Hg]. Standard oral glucose tolerance tests were performed; the logarithms of the fasting insulin level and insulin area were used in the analyses. In addition, body mass index and percent body fat (from age and skinfold thickness equations) and waist hip ratio were computed. In simple correlations, systolic BP and diastolic BP were statistically significantly related to insulin levels (only 1-4% of the variance was explained). Since age, body fat, fat distribution, insulin levels, and BP were highly intercorrelated, insulin and blood pressure correlations were examined after controlling for the confounding variables. Correlations of BP and insulin levels adjusted for age, body fat, and fat distribution were entirely nonsignificant. In this large noninterventive population study, the hyperinsulinemia-hypertension hypothesis is not confirmed. PMID- 8445010 TI - Insulin increases intracellular magnesium transport in human platelets. AB - Evidence suggests that magnesium (Mg) deficiency may play a key role in cardiovascular disease. In particular, Mg deficiency may lead to a potentiation of platelet aggregation. However, the factor(s) regulating intracellular-free Mg concentration ([Mg2+]i) in platelets is not known. We studied the effects of insulin on the changes of [Mg2+]i in human platelets. Preincubation of hirudinized platelet-rich plasma with insulin had a dose- and time-dependent effect on the increase of [Mg2+]i measured in Mag-fura-2-loaded cells with a fluorescence spectrophotometer. The maximal effect was achieved by incubation with 200 microU/mL insulin for 30 min. [Mg2+]i increased from the basal value of 266 +/- 23 mumol to 355 +/- 46 (SD, P < 0.001). In the presence of an antiinsulin receptor monoclonal antibody the effect of insulin was abolished suggesting that the Mg transport mechanism was an insulin-receptor mediated process. Furthermore, the insulin-stimulated Mg transport was inhibited by the addition of chelating agent ethylenediaminete-traacetate while the receptor binding was not altered. These findings suggest that insulin can translocate Mg from the extracellular space. Insulin alone had no effect on the changes of intracellular calcium (Ca) concentration using Ca-Fura-2 as a probe. In addition, glucose (5 mg/mL) was not effective in altering either the Mg or Ca concentration. Insulin (100 microU/mL) decreased thrombin-induced platelet aggregation (washed platelets resuspended in N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-Tyrode buffer). Similarly, the production of the proaggregatory eicosanoids thromboxane B2 was inhibited by insulin from 16 +/- 1 ng/10(8) platelets to 13 +/- 2 (P < 0.05). The results suggest that insulin, through the interactions with its receptors may be a key factor regulating, Mg transport in human platelets. PMID- 8445011 TI - Increased de novo hepatic lipogenesis in human immunodeficiency virus infection. AB - We measured de novo lipogenesis in human immunodeficiency virus (HIV) infected men using a newly developed stable isotope method. HIV-infected subjects with a history of weight loss (n = 17, mean weight loss 14.9 +/- 3.2 kg), asymptomatic HIV-seropositive subjects with normal CD4 T-cell counts (n = 7) and healthy HIV seronegative controls (n = 11) were studied. Hepatic lipogenesis was determined by infusion of [2-13C]-acetate, using the recently described xenobiotic probe technique with mass isotopomer analysis. Hepatic acetyl-coenzyme A enrichment was measured by high performance liquid chromatography/mass spectrometry of secreted sulfamethoxazole-acetate, with measurement of incorporation into very low density lipoprotein-fatty acids by gas chromatography-mass spectrometry. Circulating tumor necrosis factor (TNF), interleukin-1 (IL-1), interferon alpha (IFN alpha), insulin, and triglycerides were measured concurrently, and 7-day weighed food records were performed. De novo hepatic lipogenesis was increased 3- to 4-fold in HIV-infected subjects with weight loss compared to normal controls (P < 0.05 for palmitate and stearate in both overnight-fasted and fed states), and was also significantly increased in asymptomatic HIV seropositive subjects. Circulating TNF and IL-1 were not measurable in any subject (detection limit 2 pg/ml for IL-1 and 20 pg/ml for TNF). Serum IFN alpha was measurable in 11 out of 17 subjects with wasting and correlated significantly with de novo lipogenesis in overnight fasted but not fed states. Serum IFN alpha was unmeasurable in asymptomatic HIV infected subjects despite elevated lipogenic rates. Serum triglyceride concentrations were elevated in subjects with weight loss (2.09 +/- 0.28 mmol/L) and asymptomatic HIV-positives (1.34 +/- 0.34 mmol/L) in comparison to controls (0.67 +/- 0.08 mmol/L), and correlated with lipogenesis. Food intake correlated inversely with lipogenesis in the overnight-fasted state. We conclude that HIV infection is characterized by abnormal fat anabolism. This applies to subjects with reduced lean body mass and to asymptomatic HIV-positive subjects with normal T-cell counts. The former observation may have implications for the pathophysiology and treatment of the wasting syndrome. The latter observation is consistent with activation of the immune response and a state of viral nonlatency in early HIV disease. PMID- 8445013 TI - Factors predicting the response to growth hormone (GH) therapy in prepubertal children with GH deficiency. AB - To identify factors influencing the response to GH therapy, we used a multiple regression model to analyze data from 632 naive prepubertal children with GH deficiency (GHD). There were 523 children with idiopathic and 109 children with organic GHD. They were treated with the same preparation of biosynthetic methionyl GH (somatrem, Protropin) for at least 1 yr. In children with idiopathic GHD, six variables predicted 40% of the response to treatment. They were (listed in relative importance, all P < 0.0001): age, log maximum GH, weight adjusted for height, dosing schedule, dose, and midparental height. Three variables, pretreatment growth rate, log maximum GH, and age, predicted 20% of the GH response in children with organic GHD. When data for all children were analyzed using analysis of covariance, children with idiopathic GHD grew better than those with organic GHD (mean +/- SD, 9.2 +/- 2.4 vs. 8.8 +/- 2.6 cm/yr; P < 0.0001). The children (both organic and idiopathic GHD) who did not respond well to treatment were younger and thinner than those who did. Early diagnosis and initiation of therapy should be beneficial to ultimate height attainment. The best response to GH therapy should be in young children with severe idiopathic GHD who receive daily weight-adjusted doses. The use of GH daily in higher doses would be expected to be most beneficial in older children with acquired and/or less severe GHD or in children who are underweight for height. PMID- 8445012 TI - The roles of insulin and catecholamines in the glucoregulatory response during intense exercise and early recovery in insulin-dependent diabetic and control subjects. AB - Intense exercise is associated with a marked stimulation of glucose production (Ra), a somewhat smaller increment in its utilization (Rd) (and therefore hyperglycemia), large increases in plasma catecholamines, and moderate hyperglucagonemia. The hyperglycemia increases in recovery and is accompanied by hyperinsulinemia. Because these adaptations are unique to intense exercise, we tested the physiological significance of the hyperinsulinemia by exercising six fit, postabsorptive young male subjects with insulin-dependent diabetes mellitus (IDDM) after overnight glycemic normalization by iv insulin, keeping its infusion rate constant during and for 2 h after 100% maximum VO2 cycle ergometer exercise to exhaustion (12 min) (no postexercise hyperinsulinemia). Their responses were compared with those of matched control subjects studied on two separate occasions, once without intervention (physiological hyperinsulinemia, n = 6) and again with a 0.05 U/kg iv bolus at exhaustion (postexercise supraphysiological hyperinsulinemia, n = 5). In all three study protocols, Ra increased by 7-fold, and Rd by 4-fold at exhaustion, and Ra declined in early recovery at the same rates. Therefore, the early recovery hyperinsulinemia is not required to return Ra to preexercise levels, and excessive hyperinsulinemia does not accelerate this decline. We infer that the catecholamine increments and decrements are the prime regulators of Ra (correlations of Ra vs. norepinephrine or epinephrine, P < 0.001 in the three studies), with a smaller contribution from the concurrent hyperglucagonemia. Rd, in contrast, was significantly affected by insulin. In the IDDM subjects, Rd remained at the same rate as Ra through most of recovery, resulting in sustained hyperglycemia and decreased glucose MCR, vs. the control subjects. This hyperglycemia compensated for the abnormal MCR, such that Rd was comparable to that in the control subjects. With the insulin bolus, the Rd elevation was sustained longer compared to the study without bolus, resulting in mild hypoglycemia successfully counterregulated by an increase in Ra. Thus, the principal regulators of the marked exercise increase and rapid recovery decrease in Ra are probably the catecholamines. The postexercise hyperinsulinemia is required for the MCR response and to return plasma glucose concentrations to preexercise levels. Different therapeutic strategies are required in persons with IDDM undergoing strenuous vs. moderate exercise, because of their inability to generate the postexercise hyperinsulinemia. PMID- 8445014 TI - Amplitude suppression of the pulsatile mode of immunoradiometric luteinizing hormone release in fasting-induced hypoandrogenemia in normal men. AB - In the male rodent and primate, fasting or severe caloric restriction significantly decreases serum testosterone concentrations, putatively via inducing secondary hypogonadotrophism. To clarify this presumptive pathophysiology, we have used: 1) a high sensitivity immunoradiometric assay, which correlates well with an in vitro Leydig cell bioassay of LH; 2) blood sampling every 5 min for 24 h basally and every 10 min for 3 h after GnRH injection before and after a 5-day (water only) fast in eight healthy young men; and 3) deconvolution analysis to evaluate in vivo LH secretory burst frequency, amplitude, duration, and mass, and LH half-life simultaneously. We documented a 50% fall in serum total and free testosterone concentrations, and a 30% decrease in 24-h mean serum LH concentrations (viz., fed 3.0 +/- 0.47 vs. fasted 2.1 +/- 0.39 U/L, P = 0.043). Deconvolution analysis revealed preservation of LH secretory pulse frequency (fed 12.9 +/- 0.48 vs. fasted 12.6 +/- 0.78 secretory bursts/day, P = NS) during fasting-induced hypogonadotropism. The duration of computer-resolved LH secretory bursts, the interburst interval, and the calculated endogenous half-life of LH also did not change, whereas LH secretory burst mass declined significantly; viz. from 28 +/- 5 in the fed to 14 +/- 3.2 U/L of distribution volume/day in the fasted state (P = 0.034). In contrast, LH release after a 10 micrograms pulse of GnRH iv was enhanced during fasting in seven of the eight men. Fasting also decreased mean (24 h) serum TSH and PRL, increased cortisol, dehydroepiandrosterone sulfate and GH, and did not affect FSH concentrations or the radioiodinated albumen distribution space. In summary, in young men 5 days of nutrient deprivation selectively attenuates the mass of LH secreted per burst without altering LH secretory event frequency or LH half-life. We infer that decreased LH release per burst is due to decreased hypothalamic GnRH impulse strength, since LH release induced by a submaximally effective pulse of exogenous GnRH is amplified rather than attenuated. PMID- 8445015 TI - Estradiol amplifies the amount of luteinizing hormone (LH) secreted in response to increasing doses of gonadotropin-releasing hormone by specifically augmenting the duration of evoked LH secretory events and hence their mass. AB - Amplification of LH release during the preovulatory LH surge could result from increased GnRH secretion and/or estradiol's facilitation of the dose-dependent actions of GnRH. We have investigated the mechanisms of estrogen's enhancement of GnRH action by evaluating LH release in response to four consecutive iv doses of GnRH (7.5, 25, 75, and 250 ng/kg) administered in randomized order followed by a fifth (maximal) dose of 750 ng/kg GnRH. The GnRH dose-response study was carried out before and after 10 days of estradiol treatment (0.2 mg/day percutaneously) in nine healthy postmenopausal women. Deconvolution analysis was used to quantitate specific measures of GnRH-stimulated LH secretion as well as estimate the half-life of endogenous LH. We found that 10 days of estradiol delivery did not alter the calculated half-life of immunoradiometric LH (126 +/- 10 min basally vs. 135 +/- 14 min during estrogen), but amplified the total mass of LH secreted in response to the five doses of GnRH; viz. 201 +/- 29 (control) vs. 406 +/- 58 IU/L (estrogen) (P < 0.001). Estradiol specifically enhanced the maximal value of the GnRH dose-LH secretory response curve; viz. from a mass of LH secreted of 46 (41-51) IU/L (basal) vs. 113 (93-139) IU/L (estrogen) (P < 0.001). Estradiol did not induce a significant leftward shift of the GnRH dose-LH secretory response curve, since the half-maximally effective dose of GnRH (ED50) was 9 (3.6-18) (control) vs. 19 (10-31) ng/kg (estradiol). The increased mass of LH secreted in the estrogen-rich milieu was due to a doubling of LH secretory burst duration, with no change in amplitude. We conclude that amplified LH secretory burst duration constitutes a novel neuroendocrine mechanism by which estradiol can promote GnRH self-priming of LH release by the previously estrogen deprived human anterior pituitary gland in vivo. PMID- 8445016 TI - Androgen and estrogen dynamics: relationships with age, weight, and menopausal status. AB - Previous studies have shown a relationship between age and weight and the MCR and conversions ([rho]) of androgens and estrogens. To assess the relative importance of these relationships in the metabolism and conversion of the androgens and estrogens, we used a series of statistical analyses, including t test, Pearson's correlation, and a step-wise regression analysis of the data obtained from the constant infusion of radiolabeled androgens and estrogens to normal women, 18-90 yr old. The MCRs of testosterone (T), androstenedione (A), and estrone (E1) were strongly correlated with weight, but not age or menopausal status. The MCR of estradiol (E2) was strongly correlated with weight and less strongly correlated with age, but was not correlated with menopausal status. The interconversions of the androgens ([rho]T,ABB and [rho]A,TBB, i.e. percentage of precursor infused measured as product in blood) and estrogens ([rho]E1,E2BB and [rho]E2,E1BB) were not correlated with age or weight, but there was a weak correlation between [rho]T,ABB and menopausal status. The aromatization of androgens to estrogens ([rho] A,E1BM and [rho]T,E2BM, i.e. percentage of androgens infused measured as estrogen glucuronide in the urine) was highly correlated with age, less strongly correlated with weight, and not correlated with menopausal status. The correlation with weight and MCR is a reflection of the extrasplanchnic metabolism of steroids. The lack of correlation with weight for the interconversions of androgens and estrogens indicates that the enzyme(s) responsible is affected differently in extrasplanchnic tissue than is the aromatase complex. The relationship between age and aromatization, while strong, remains unexplained. PMID- 8445017 TI - Evidence of thyroid volume increase in normal subjects receiving excess iodide. AB - A prospective study was conducted on 10 normal male volunteers to investigate the effect of the administration of excess iodide on thyroid volume. After 1 week of dietary iodide restriction, all subjects were given daily oral doses (27 mg daily total iodine dose) of licorice lecithin-bound iodine tablets for 4 weeks. Thyroid function studies, total serum iodine concentration, and urinary iodine excretion were monitored. Thyroid volume was measured by high resolution echoscanner before treatment, on the day of the last treatment, and 1 month after the treatment. There was a significant rise in serum TSH levels, with a small decline in serum free T4 concentration during iodide administration; the values remained within the normal range except for two subjects. Serum thyroglobulin levels were increased in parallel with serum TSH levels, which became higher than normal after 1 week of treatment. The volume of the thyroid gland became significantly enlarged after 28 days of iodide intake. When iodide was discontinued, thyroid volume and function returned to baseline levels within 1 month for all subjects. This is the first documentated objective evidence that the compensatory rise in serum TSH in response to iodide administration elicits reversible thyroid hypertrophy in normal subjects. PMID- 8445018 TI - Endothelins stimulate the synthesis and release of prorenin from human decidual cells. AB - The factors that regulate the synthesis and release of renin by human decidua and other extrarenal tissues are poorly understood. Recent studies have demonstrated that the potent vasoconstrictive peptide endothelin (ET) inhibits the release of renin from renal juxtaglomerular cells, probably by a calcium-dependent mechanism. To determine whether ET also influences the release of renin from decidual tissue, we have examined the effects of ET on the synthesis and release of renin by primary cultures of human decidual cells. Decidual cells exposed continuously to ET (10(-7) mol/L) for 96 h released significantly more renin than control cells. At 48, 72, and 96 h, the ET-exposed cells released 284, 645, and 1300% more renin, respectively, than control cells. Greater than 95% of the renin released into the medium was in the form of prorenin, the precursor of renin. The stimulation by ET was dose-dependent, with half-maximal stimulation at a concentration of 7 x 10(-9) mol/L. ET-2 and ET-3, as well as the precursor to ET (big ET), also stimulated renin release. The total amount of renin in the media and cells of ET-exposed decidual cells was significantly greater than that of control cells, indicating that the increase in renin release was accompanied by an increase in synthesis. In addition, Northern blot analysis of total RNA from cells exposed for 96 h to ET-1 (10(-7) mol/L) indicated that the renin messenger RNA content of ET-1-exposed cells was approximately 100 times greater than that of control cells. These results indicate that ET is a potent stimulus to the synthesis and release of prorenin from human decidua and that the effect of ET on decidual renin expression is opposite to that observed for the expression of renal renin. PMID- 8445019 TI - Point mutation in a family with hyperproinsulinemia detected by single stranded conformational polymorphism. AB - We previously described a case of familial hyperproinsulinemia, the fifth to be reported. In the present study we characterized the genetic defect carried by this family and demonstrated that it could be detected by polymerase chain reaction-single stranded conformational polymorphism. Since the serum proinsulin molecule from the propositus, a 63-yr-old Japanese man, was eluted on the same fraction of human proinsulin intermediate cleaved only at the B-C junction, we sequenced exon 3 of his insulin gene, including the C-A junction. A point mutation was discovered that changed codon 65 from arginine (CGT) to histidine (CAT) in one allele. This was the same point mutation as that described previously in three unrelated kindreds representing two races, consistent with the hypothesis that the dinucleotide sequence CpG may be a "hot spot" for mutations. Recently, developed polymerase chain reaction-single stranded conformational polymorphism proved useful in detecting this mutation in the family members. The daughter of the propositus and one of his two grandsons were also demonstrated to be heterozygous for this point mutation by this method. PMID- 8445020 TI - Evidence for attenuation of hypothalamic gonadotropin-releasing hormone (GnRH) impulse strength with preservation of GnRH pulse frequency in men with chronic renal failure. AB - To investigate the nature of putative disturbances in pulsatile gonadotropin (LH) secretion in men with chronic renal failure, we undertook blood sampling at 10 min intervals for 24 h in 9 hemodialysis-dependent uremic men and 16 community- and age-matched controls. Serum LH concentrations were measured in a 2-site immunoradiometric assay, which does not cross-react with free alpha or LH beta subunit and correlates well with an in vitro Leydig cell bioassay. Deconvolution analysis was applied to calculate the number, amplitude, mass, and duration of spontaneous LH release episodes and simultaneously estimate the half-life of endogenous LH in each subject. We observed that: 1) the estimated half-life of immunoradiometric LH removal from plasma averaged 103 +/- 11 min in normal and 207 +/- 29 min in uremic men (P < 0.01); 2) the number of LH secretory bursts was slightly higher in uremic than healthy men (e.g. 20 +/- 2.2 vs. 15 +/- 1.0 secretory bursts/24 h, respectively; P = 0.05); 3) the mass of LH secreted per burst was approximately 50% lower in chronic renal failure than in health, namely 1.4 +/- 0.18 vs. 2.8 +/- 0.42 IU/L (P < 0.01); 4) the decrease in the mass of LH secreted per burst was not due to a decline in LH secretory burst amplitude, but rather an attenuation of LH secretory burst duration (4.8 +/- 0.35 min in uremic vs. 11 +/- 1.3 min in normal men; P < 0.001); 5) the mean 24-h serum immunoradiometric LH concentration was significantly higher in uremia at 5.7 +/- 0.68 vs. 3.6 +/- 0.41 IU/L in controls (P = 0.017); and 6) serum estradiol concentrations were increased in uremia, but total and free testosterone concentrations did not differ significantly between the two subject groups. In response to synthetic GnRH (10 micrograms, administered iv after the 24-h basal sampling period), the mean mass of immunoradiometric LH released within each calculated LH secretory burst was similar in uremic (n = 8) and normal (n = 21) individuals. We conclude that uremia is accompanied by a specific defect in the pulsatile mode of LH secretion, which is marked by an abbreviation of LH secretory burst duration and a consequent fall in the mass of LH secreted per spontaneous release episode. There is no overall decline in LH secretory pulse frequency or gonadotroph responsiveness to a submaximally effective dose of exogenous GnRH. Such findings are consistent with diminished hypothalamic GnRH impulse strength.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8445021 TI - C-peptide during the prolonged fast in insulinoma. AB - C-Peptide, a marker for insulin secretion, is purported to be elevated in patients with insulinoma but diagnostic criteria have not been established. Thirty-seven patients with histologically confirmed insulinoma studied preoperatively, 19 normal subjects, and 2 patients who subsequently acknowledged self-administration of insulin underwent the prolonged fast (< or = 72 h) according to a standard protocol. Plasma glucose, C-peptide, and insulin were measured every 6 h until plasma glucose was less than or equal to 3.3 mmol, then hourly until Whipple's triad was demonstrated or until 72 h without symptoms was reached. At the termination of the fasts, plasma was analyzed for sulfonylurea. Statistical analysis was by rank sum test. Data are expressed as median (range). The durations of fasts were 20 (2.5-68) h for patients with insulinomas and 72 h for normal subjects. At the end of fasts plasma glucose, C-peptide, and insulin concentrations were 2.2 (1.4-2.9) vs. 3.6 (2.7-5.5) mmol, P < 0.001; 0.60 (0.20 1.92) vs. 0.13 (0.07-0.43) nmol, P < 0.001; and 126 (35-840) vs. 35 (35-126) pmol, P < 0.001, respectively, for insulinoma patients and normal subjects. All plasma samples were negative for sulfonylurea. Insulinoma patients had C-peptide values at the end of the fasts greater than or equal to 0.20 nmol whereas normal subjects and patients with insulin factitial hypoglycemia had C-peptide concentrations less than or equal to 0.10 nmol when plasma glucose was less than or equal to 2.8 mmol. Insulinoma is confirmed in a sulfonylurea negative patient with Whipple's triad during the prolonged fast and a concomitant C-peptide concentration greater than or equal to 0.20 nmol. PMID- 8445023 TI - Pulsatile characteristics of spontaneous growth hormone (GH) concentration profiles in boys evaluated by an ultrasensitive immunoradiometric assay: evidence for ultradian periodicity of GH secretion. AB - To investigate underlying ultradian periodicities in spontaneous circulating GH concentration, blood samples were drawn from 15 normal short boys every 20 min over a 24-h period, and plasma GH concentrations were measured using an ultrasensitive immunoradiometric assay. The limit of detection for the GH assay was 0.01 microgram/L. The GH time series were analyzed using the Cluster program, Ultra program, cosinor analysis, and autocorrelation analysis. Plasma GH concentrations in 1095 samples derived from 15 normal short boys were all within the detectable range of the assay and ranged from 0.07-52.2 micrograms/L. Thirty six percent of the GH values in the 1095 samples from 15 normal short boys were below 1 microgram/L, and 82% of them occurred during the diurnal awakening period. Cluster analysis disclosed a total of 176 peaks in 15 normal short boys, with a mean +/- SEM number of significant GH peaks of 12.1 +/- 0.5/24 h. Twelve percent of the 176 peaks were below 1 microgram/L, and 95% of them occurred during the diurnal awakening period. In addition, Cluster analysis disclosed 161 interpulse intervals in total, with a mean +/- SEM interval of 116.5 +/- 4.3 min. The GH interpulse interval did not show a significant 24-h rhythm, whereas the GH peak height increased significantly at night. An independent discrete peak detection program, Ultra, identified 12.6 +/- 0.5 GH peaks/24 h. This result was in good agreement with that from analysis by the Cluster program (P = NS). Autocorrelation analysis revealed that GH time series were significantly autocorrelated in 9 of the 15 boys, with maximal autocorrelation coefficients at 115.5 min, on the average. The mean autocorrelation coefficient for a group of 15 normal short boys was significantly positive at a 100-min lag. These findings suggest that there could be a regularly occurring periodicity of approximately 100-120 min in the human GH time series. PMID- 8445022 TI - T-cell receptor V gene use in autoimmune thyroid disease: direct assessment by thyroid aspiration. AB - We have examined the hTcR V gene family use of T-cells present in the aspiration thyroid biopsy specimens of patients with hyperthyroid Graves' disease (n = 8) and Hashimoto's autoimmune thyroiditis (n = 5). Nine of the 13 specimens had cytologically identified thyroid follicular cells, and 12 of the 13 contained human thyroglobulin-specific mRNA, confirming successful sampling. Of 18 hTcR V alpha and 19 hTCR V beta gene families tested for in the individual aspirates, a mean +/- SEM of 6.8 +/- 0.9 V alpha and 9.6 +/- 1.4 V beta gene families were present in the Graves' aspirates, while 12.2 +/- 1.7 and 16.8 +/- 0.4 V alpha and V beta gene families were present in the aspirates of patients with Hashimoto's thyroiditis. These samples, which offer a window onto the natural history of autoimmune thyroid disease, demonstrate significant hTcR V alpha and beta gene restriction in hyperthyroid Graves' disease, but much less restriction of both V alpha and V beta gene families in Hashimoto's disease. Such data extend our earlier information based only on examination of highly selected surgical specimens of patients with autoimmune thyroid disease to the much more typical patient. We conclude that hTcR V gene restriction of varying degrees is present in the majority of patients with autoimmune thyroid disease, but appears to be more easily detected in Graves', rather that Hashimoto's, disease. PMID- 8445024 TI - Thyroid function in women with premenstrual syndrome. AB - We have examined the relationship between thyroid function and the presence of symptoms in women with prospectively confirmed premenstrual syndrome (PMS) in the following ways: 1) basal thyroid function tests (n = 124); 2) thyroid auto antibody levels (n = 63); 3) TRH stimulation tests performed during the follicular phase (n = 39) or during both the follicular and luteal phase (n = 21); and 4) the efficacy of L-T4 in the treatment of PMS (n = 30). RESULTS: Thirteen women (10.5%) had basal evidence of either grade I or II hypothyroidism or hyperthyroidism. Elevated thyroid auto-antibody titers were observed in eight women (13%). Eighteen women (30%) (all with normal basal TSH levels) had abnormal responses to TRH, either blunted (n = 6) or exaggerated (n = 12). L-T4 was not superior to placebo in the treatment of PMS in a double blind placebo controlled cross-over trial. Although it is clear that PMS is not simply masked hypothyroidism, abnormalities of stimulated thyroid function appear with greater than expected frequency in women with PMS and may define a subgroup of women with this disorder. L-T4 supplementation appears to have no place in the routine management of PMS. PMID- 8445025 TI - Normal dexamethasone suppression in obese binge and nonbinge eaters with rapid weight loss. AB - Natural or experimental starvation is frequently associated with hypercortisolism, reflected as incomplete suppression of serum cortisol after dexamethasone. To determine whether rapid weight loss per se or some other aspect of starvation induces disruption of the hypothalamic-pituitary-adrenal (HPA) axis, we evaluated 2 categories of obese women (body mass index > 30 kg/m2) undergoing rapid weight loss: binge eaters (n = 12) and nonbinge eaters (n = 8). We performed psychometric evaluation and 1 mg overnight dexamethasone suppression tests in the obese subjects, as well as in 12 race- and age-matched normal-weight women. The obese women were tested before and after 12 weeks of a 3349 kJ/day (800 kcal/day) liquid formula diet, and lost an average of 19.3 kg, which represented 17.3% of their total body weight. Binge eaters, who were initially more depressed than either nonbinge eaters or normal-weight controls, had a significant amelioration of their symptoms with weight loss. Neither group had evidence of disruption of the HPA axis before or after weight loss. Thus, the rate of failure to suppress cortisol after dexamethasone was approximately 10% in each of the obese and control groups, and did not differ between the pre- and postweight loss condition or between binge eaters and nonbinge eaters. Serum free T4 was unchanged, whereas T3 fell significantly with weight loss. We conclude that weight loss may improve affect in the obese without altering HPA axis activity, and postulate that one of the concomitants of restricted energy intake, perhaps in combination with a threshold body weight, may be of greater importance in causing abnormalities of dexamethasone suppression testing than rapid weight loss per se. PMID- 8445026 TI - Quantitation of thyroid hormone effect on skin perfusion by laser Doppler flowmetry. AB - Clinical observations have long suggested that skin perfusion (SP), among other factors, depends on thyroid status. However, quantitative data concerning this relationship are rather sparse. This study characterizes SP by means of laser Doppler flowmetry (LDF) in various thyroid dysfunctional states. The data reveal that mean capillary flow velocity, capillary pulse wave amplitude, and capillary flow oscillation amplitude, but not capillary flow oscillation frequency, are increased in hyperthyroid patients and decreased in hypothyroid patients. Regaining the euthyroid state is accompanied by normalization of LDF parameters only in hyperthyroid patients. It is concluded that LDF is useful in monitoring the thyroid effect on SP. However, it may not be used as a biological marker for the thyroid status of a given individual. PMID- 8445028 TI - The role of progesterone in regulating human granulosa cell proliferation and differentiation in vitro. AB - To further elucidate the role of progesterone in regulating granulosa cell function, human granulosa and luteal cells were obtained from follicular aspirates of women undergoing in vitro fertilization and placed in culture. Cells plated at 5 x 10(3) cells/mL doubled after 3 days. In contrast, cells plated at 50 x 10(3) cells/mL did not proliferate, but differentiated, secreting high levels of progesterone. Cells plated at 5 x 10(3) cells/mL and cultured with spent medium from cells plated at 50 x 10(3) cells/mL did not increase in number over 3 days of culture. The growth-inhibiting action of the spent medium was removed by either RU 486 (a progesterone receptor antagonist) or charcoal extraction, but not by heat inactivation. The addition of progesterone to fresh medium also prevented cell proliferation. Progesterone's ability to inhibit cell division was attenuated by either RU 486 or aminoglutethamide, which blocked progesterone synthesis. Further, epidermal growth factor (EGF) stimulated cell proliferation, and continuous exposure to progesterone blocked EGF-induced mitosis. When progesterone was added 2 h after EGF, it did not block EGF stimulated cell proliferation. Progesterone also increased the percentage of granulosa cells and decreased the percentage of large luteal cells present after 3 days of culture, indicating that progesterone inhibited differentiation. Progesterone's effect on differentiation was dose dependent, reversible, and could be overridden by hCG or 8-bromo-cAMP. These observations suggest that progesterone acts directly on granulosa cells through its receptor to inhibit mitosis and that progesterone mediates its antiproliferative effects within 2 h of mitotic stimulation. Progesterone also blocks differentiation, but this effect of can be overcome by hCG or cAMP analogs. These data indicate that progesterone plays a major role in controlling the number of luteal cells that ultimately develop within a corpus luteum by regulating both granulosa cell proliferation and differentiation. PMID- 8445027 TI - Familial glucocorticoid resistance caused by a splice site deletion in the human glucocorticoid receptor gene. AB - The clinical syndrome of generalized, compensated glucocorticoid resistance is characterized by increased cortisol secretion without clinical evidence of hyper- or hypocortisolism, and manifestations of androgen and/or mineralocorticoid excess. This condition results from partial failure of the glucocorticoid receptor (GR) to modulate transcription of its target genes. We studied the molecular mechanisms of this syndrome in a Dutch kindred, whose affected members had hypercortisolism and approximately half of normal GRs, and whose proband was a young woman with manifestations of hyperandrogenism. Using the polymerase chain reaction to amplify and sequence each of the nine exons of the GR gene alpha, along with their 5'- and 3'-flanking regions, we identified a 4-base deletion at the 3'-boundary of exon 6 in one GR allele (delta 4), which removed a donor splice site in all three affected members studied. In contrast, the sequence of exon 6 in the two unaffected siblings was normal. A single nucleotide substitution causing an amino acid substitution in the amino terminal domain of the GR (asparagine to serine, codon 363) was also discovered in exon 2 of the other allele (G1220) in the proband, in one of her affected brothers and in her unaffected sister. The functional importance of this mutation was tested in a cotransfection study using the recombinant expression vector pRShGR-Ser363 and the glucocorticoid responsive vector mouse mammary tumor virus-chloramphenicol transferase. This amino acid substitution did not alter the function of the glucocorticoid receptor. Using reverse transcription-polymerase chain reaction we could only identify messenger RNA transcripts of the G1220-allele but not of the delta 4-allele in the affected members of this family who were heterozygous for the G1220 mutation. This deletion in the glucocorticoid receptor gene was, thus, associated with the expression of only one allele and a decrease of GR protein by 50% in affected members of this glucocorticoid resistant family. The mutation identified in exon 2 did not segregate with the disease and appears to be of no functional significance. The presence of the null allele was apparently compensated for by increased cortisol production at the expense of concurrent hyperandrogenism. PMID- 8445029 TI - Interleukin-1 beta stimulates colony-stimulating factor-1 production in human term placenta. AB - The human placenta produces hematopoietic growth factors including colony stimulating factor-1 (CSF-1). We have previously demonstrated Interleukin-1 beta (IL-1 beta) production by decidualized endometrium during pregnancy. Since IL-1 beta stimulates CSF-1 production in a variety of mesenchymal cell types including second trimester villous core mesenchymal cells, the present study was designed to determine if IL-1 beta could also regulate CSF-1 production in term placental explants in vitro. Placental villous explants from normal term placentas (n = 5) were cultured with or without recombinant human IL-1 beta. A dose response relationship between increased added IL-1 beta and increased CSF-1 production as measured by enzyme-linked immunosorbent assay was observed with 1 ng/mL IL-1 beta being the lowest dose to significantly increase CSF-1 production (P < 0.01). In time course experiments, 10 ng/mL maximally induced CSF-1 messenger RNA expression 2.7 fold (P < 0.005) compared to controls at 8 h of culture as determined by dot blot analysis. Production rates of CSF-1 were linear up to 24 h at which time IL-1 beta (10 ng/mL)-treated samples had 1.7-fold higher levels of CSF-1 in the media than nontreated controls (8.38 ng/gm tissue vs. 4.94 ng/gm tissue, P < 0.01). These results demonstrate that IL-1 beta can regulate placental CSF-1 production in vitro and suggest that maternal decidual IL-1 beta may regulate placental CSF-1 production in vivo. PMID- 8445030 TI - The deactivation of hCG by nicking and dissociation. AB - Human chorionic gonadotropin (hCG) is composed of an alpha- and a beta-subunit, joined noncovalently. A proportion of hCG molecules in pregnancy serum and urine samples have nicks or a missing peptide linkage between either beta-subunit residues 44 and 45 or beta-subunit residues 47 and 48. These nicks ablate the steroidogenic activity of hCG. We examined the source of nicking, and the occurrence and stability of nicked hCG molecules produced during pregnancy. We investigated the source of nicking. Standard hCG was added to three samples of whole blood, and incubated 18 h at 37 C. No change in extent of nicking was detected. However, nicking of hCG beta-subunit was detected by gel electrophoresis (bands at M(r) = 17,000 and M(r) = 22,000, corresponding to the peptides beta 1-47(44) and beta 48(45)-145, respectively) in culture fluids from first trimester placental explants and from JAr malignant trophoblast cells. We inferred that nicking occurs before or immediately upon secretion by trophoblast tissue. We examined the occurrence of nicking. Levels of total hCG (nicked+nonnicked) and intact hCG (nonnicked) were determined in 233 serum and 168 urine samples from 4-40 weeks of pregnancy. From the two measurements the extent of nicking was estimated. A linear relationship was indicated between advancing weeks of gestation and increasing extent of nicking (regression analysis, months vs. percent nicked, 95% correlation). Minimum nicking was observed in serum from the first 2 months of pregnancy (mean = 9% of hCG molecules), increased nicking in the months after, and maximum nicking in samples from the last 2 months of pregnancy (mean = 21% of hCG molecules, t test first 2 months vs. last 2 months, P < 0.00005). Similar results were observed with urine samples (first 2 months mean = 9%, last 2 months = 27%, t test P < 0.00005). We concluded that nicking is more prevalent after the hCG peak (after 2 months of pregnancy). Finally, we examined the stabilities of nicked and intact hCG molecules. Standard hCG (batch CR127, 20% nicked) and hCG preparation C5 (100% nicked) were incubated for varying times in whole blood. C5 hCG dissociated rapidly into free alpha- and beta-subunits (dissociation half-life 22 +/- 5.2 h), over 30 times faster than standard hCG (dissociation half-life 700 h).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8445031 TI - Gonadotropin-releasing hormone agonist-induced differences in granulosa cell cycle kinetics are associated with alterations in follicular fluid mullerian inhibiting substance and androgen content. AB - We have previously shown that the proliferative index (PI), as determined by flow cytometry of luteinized granulosa cells obtained at oocyte retrieval, is greater in ovulation induction regimens which include the GnRH analog (GnRH-a) leuprolide acetate than those using human menopausal gonadotropin (hMG) only. Specific growth factors or intrafollicular hormones may contribute to this leuprolide acetate-induced difference in cell cycle kinetics. We examined whether differences in the PI of these granulosa cells are associated with the alterations of follicular fluid content of Mullerian-inhibiting substance (MIS) and other intrafollicular hormones including FSH, estradiol, progesterone, androstenedione, and testosterone. The control group consisted of follicular fluid obtained from 18 follicles from 4 women receiving hMG alone. The GnRH-a treated group consisted of follicular fluids obtained from 55 follicles aspirated from 18 women receiving GnRH-a in addition to hMG. One-way analysis of variance using log-transformed data and expressed as geometric means with 95% confidence intervals, demonstrated that the follicles from the control group had a significant 14-fold higher concentration of 2.46 ng/mL MIS, 95% CI (1.8-4.8) vs. 0.18 ng/mL, 95% CI (0.13-0.24) P < 0.0005, a 3-fold higher concentration of 17.55 nmol/L androstenedione, 95% CI (14.6-20.9) vs. 5.76 nmol/L, 95% CI (3.1-10.5) P < 0.02, and a 1.5-fold higher concentration of 29.43 nmol/L testosterone 95% CI (22.5-38.14) vs. 19.3 nmol/L, 95% of CI (11.1-33.9) P < 0.01 than GnRH-a treated follicles, although the PI value in controls was half that of the GnRH-a group. These data demonstrate that GnRH-a induced differences in granulosa cell cycle kinetics are associated with alterations of MIS and androgen intrafollicular fluid content and suggest that MIS may be a mitotic inhibitor of human granulosa cells. PMID- 8445032 TI - Calcium infusion suggests a "set-point" abnormality of parathyroid gland function in familial benign hypercalcemia and more complex disturbances in primary hyperparathyroidism. AB - PTH clearly plays a role in maintaining the hypercalcemia of familial benign hypercalcemia (FBH or familial hypocalciuric hypocalcemia). To better define the abnormalities of parathyroid function in FBH and primary hyperparathyroidism (1 degree HPT), we used a two-site immunochemiluminometric assay for intact PTH to examine PTH suppressibility in normal individuals and patients having FBH or 1 degree HPT. Twelve normal, 11 FBH, and 7 1 degree HPT subjects were given calcium (Ca) iv with frequent sampling for ionized Ca and intact PTH. In normal and FBH subjects, plasma PTH levels decreased essentially identically in response to iv Ca. In the 1 degree HPT group, PTH was not normally suppressible. However, there was a spectrum of responsiveness in 1 degree HPT patients, with a significant correlation between tumor mass and degree of PTH nonsuppressibility (r = 0.87, P = 0.01). Analysis of the relationship between plasma PTH and ionized Ca values in the three groups demonstrated a shift to the right in the FBH curve, with no difference of slope, consistent with the notion of a simple "set-point" error in FBH. In contrast, the curve in 1 degree HPT was not only shifted to the right but also differed from normal in slope (normal, -8.92; 1 degree HPT, -3.92, P = 0.04). Thus, we propose that the parathyroid functional abnormality in FBH represents a simple set-point error, whereas the defect in 1 degree HPT consists of a set-point error combined with varying degrees of Ca nonsuppressible PTH secretion that may be related to tumor mass. PMID- 8445033 TI - Tumor necrosis factor-alpha prevents the differentiation of human adipocyte precursor cells and causes delipidation of newly developed fat cells. AB - We investigated the effect of the tumor necrosis factor-alpha (TNF alpha) on the differentiation of human adipocyte precursor cells in primary culture. Adipocyte precursors convert into fat cells within 12-16 days in a chemically defined, hormone-supplemented medium. Exposure of cultured preadipocytes to TNF alpha resulted in a dose- and time-dependent decrease in the number of developing fat cells and the activity of glycerol-3-phosphate dehydrogenase (GPDH), an established marker of adipocyte differentiation. A 24-h incubation with TNF alpha at a concentration of 5 nM suppressed GPDH activity by 55% compared to that in control cultures. Continuous exposure of the cells to TNF alpha completely blocked expression of the adipocyte phenotype and GPDH activity. The inhibitory action of TNF alpha was not associated with a change in cell number, as assessed by cell counting. The addition of 5 nM TNF alpha for 24 h to newly developed fat cells caused a rapid reduction of GPDH activity by approximately 50%. A 14-day exposure of differentiated cells to TNF alpha was followed by complete suppression of GPDH and a marked delipidation of the cells, including morphological changes, leading to the development of long spindle-shaped cytoplasmatic extensions. These results clearly demonstrate that TNF alpha inhibits the differentiation of human adipocyte precursor cells and, in addition, promotes the delipidation of mature fat cells. It is suggested that TNF alpha may be involved in the physiological control of human adipose tissue cellularity and function. PMID- 8445034 TI - 11 beta-Hydroxysteroid dehydrogenase deficiency and glucocorticoid status in patients with alcoholic and non-alcoholic chronic liver disease. AB - 11 beta-Hydroxysteroid dehydrogenase (11 beta HSD), found predominantly in liver and kidney, is responsible for the shuttling of active cortisol to cortisone. A defect in this shuttle mechanism, e.g. after liquorice ingestion, results in an increase in the ratio of urinary cortisol [tetrahydrocortisol (THF)] to cortisone [tetrahydrocortisone (THE)] metabolites. The plasma cortisol half-life is prolonged, but concentrations remain normal because of a concomitant fall in cortisol production. Alcohol-induced pseudo-Cushing's syndrome is an ill defined cause of Cushing's syndrome. Because many of the documented cases have abnormal liver function tests, we have investigated whether abnormal hepatic 11 beta HSD activity may play a role in the pathogenesis of the condition. Fourteen patients with alcoholic (ALD) and 14 patients with non-alcoholic (CLD) chronic liver disease had marked deficiency of 11 beta HSD [5 alpha-THF + THF/THE: ALD, 1.94 +/ 0.38 (+/- SEM); CLD, 1.82 +/- 0.20] compared to controls (0.94 +/- 0.04; P < 0.01 and 0.001, respectively). In the CLD group, the daily cortisol production rate (as assessed by summation of principal cortisol metabolites) was reduced appropriately [median, 3,510; range, 1,101-8,940 micrograms/24 h; controls, 5,492 (range, 3,818-14,996) micrograms/24 h; P < 0.001], and normal 0900 h plasma cortisol and urinary free cortisol levels were maintained. However, in the ALD group, there was no concomitant fall in the cortisol production rate (sum of cortisol metabolites, 5,043 micrograms/24 h; range, 520-27,344). As a consequence, 0900 h plasma cortisol in the ALD group was significantly elevated (633 +/- 52 nmol/L) compared to values in the CLD group (487 +/- 48 nmol/L; P < 0.05) and controls (432 +/- 27 nmol/L; P < 0.001). Our findings of glucocorticoid excess in patients with chronic ALD may indicate that alcohol-induced pseudo Cushing's syndrome develops as a result of continuing normal cortisol secretion in the face of impaired cortisol metabolism. The latter is mediated by defective hepatic 11 beta HSD activity; the former by either abnormal glucocorticoid feedback or stimulation of cortisol secretion at the level of the hypothalamus/pituitary. PMID- 8445035 TI - Octreotide reverses hyperinsulinemia and prevents hypoglycemia induced by sulfonylurea overdoses. AB - Emergency therapy of sulfonylurea overdoses with glucose is often unsatisfactory because glucose stimulates insulin release and initiates a need for escalating quantities of hypertonic glucose to maintain normoglycemia. We tested the hypothesis that octreotide, an analog of somatostatin, would reverse hyperinsulinemia induced by a sulfonylurea overdose. Eight normal subjects received glipizide (1.45 mg/kg) on three occasions. Within 3 h, all subjects became hypoglycemic (< 50 mg/dL) and were initially treated with 50% dextrose followed by 1) dextrose infusion, 2) octreotide (30 ng/kg.min, iv), or 3) diazoxide (300 mg, iv, every 4 h). Euglycemia (85 mg/dL) was maintained with supplementary dextrose in treatment limbs 2 and 3. Insulin concentrations were 4 5 times greater with dextrose alone or in combination with diazoxide than with octreotide (P < 0.01). Dextrose requirements during diazoxide or dextrose alone were not different, but were both greater than those during octreotide treatment (P < 0.0001). All therapies were stopped at 13 h. Glucose levels remained above 3.6 mmol/L (65 mg/dL) in six of eight subjects receiving octreotide for the remaining 4 h. Glucose fell to below 3.6 mmol/L within 1.5 h of stopping either dextrose or diazoxide in each subject. Overall, octreotide reduced and in four of eight subjects entirely eliminated the need for exogenous glucose after a large overdose of glipizide. We conclude that octreotide is safe and effective and should be strongly considered as a logical therapeutic alternative for this metabolic emergency. PMID- 8445036 TI - Cellular localization of membrane metalloendopeptidase (enkephalinase) in human endometrium during the ovarian cycle. AB - Previously, we found that membrane metalloendopeptidase (MMEP; enkephalinase) is present in human endometrium where it may inactivate certain bioactive peptides such as endothelin. The specific activity of MMEP in endometrium is correlated positively with the level of plasma progesterone. In the present study, we determined the cellular distribution of MMEP immunoreactivity (IR) in samples of endometrium from 31 ovulatory women at different phases of the menstrual cycle and from 5 postmenopausal women. At all times, MMEP-IR was localized in the endometrial stromal cells and was absent from myometrium, epithelia, and vessels. The presence of the enzyme on the stromal cell plasma membrane was demonstrated by immunostaining of freshly isolated endometrial stromal cells. During the endometrial cycle, there were dramatic changes in MMEP-IR in the zona functionalis: In the proliferative phase when plasma progesterone levels were low, MMEP-IR was weak; but after ovulation, during the early and midsecretory phases, when progesterone levels were increasing or high, MMEP-IR was strong. During the late secretory phase, in the stromal areas that were decidualized, contiguous with spiral arterioles and beneath the surface epithelium, most of the MMEP-IR was lost, whereas MMEP in the other stromal areas remained strong. In the premenstrual phase, there was a more generalized decline in MMEP-IR in the stromal cells. MMEP-IR in the zona basalis was weak to moderate and was relatively unchanged during the ovarian cycle; the findings in postmenopausal tissues were similar to those of proliferative phase tissues. These results are consistent with the previous findings of increased MMEP mRNA, protein, and activity in endometrial tissue of midsecretory phase and in cultured endometrial stromal cells in response to progestin. Furthermore, in this study, we demonstrate that in the late secretory phase in decidualizing stroma, MMEP-IR is decreased considerably compared with midsecretory stromal cells. These changes in MMEP-IR are consistent with the possibility that endothelin, also produced in endometrium, is spared inactivation in the premenstrual phase and may act on the spiral arterioles. These findings are supportive of a role for MMEP in paracrine interactions affecting vascular homeostasis in the endometrium. PMID- 8445037 TI - Xanthoma disseminatum, a rare cause of diabetes insipidus. AB - A 33-yr-old male developed typical symptoms and findings of diabetes insipidus. A computed tomographic scan of the hypothalamus/pituitary was normal, and he was diagnosed as having idiopathic diabetes insipidus. At age 38 yr, he developed two 1- to 2-mm reddish papules on his skin. Biopsy revealed infiltrative histiocytes laden with lipid. Bone scans and bone x-rays showed widespread osteolytic and osteoblastic disease. The disease was diagnosed as a rare disseminated histiocytic disorder, xanthoma disseminatum. A classification of histiocytic disease is presented. PMID- 8445038 TI - Expression of luteinizing hormone-releasing hormone mRNA in the human prostatic cancer cell line LNCaP. AB - Recent evidence suggests that LHRH or a LHRH-like peptide might be produced by human prostatic tumor cells. To test this hypothesis, we have studied whether a mRNA for LHRH is expressed in the human prostatic cancer cell line LNCaP, by means of the RT-PCR (reverse transcription-polymerase chain reaction) technique. For these experiments, mRNA was extracted from LNCaP cells, from rat hypothalami and from rat pituitaries, reverse transcribed to cDNA and amplified via the PCR utilizing a pair of oligonucleotide primers complementary to the LHRH cDNA. Following gel electrophoresis, a band of the expected size of 228 base pairs was found in LNCaP cells as well as in the rat hypothalamus, but not in the rat anterior pituitary. This 228 base pair band from LNCaP cells and from the rat hypothalamus specifically hybridized to a 32P-labeled LHRH oligonucleotide probe. The cDNA band obtained from LNCaP cells was subcloned into a plasmid vector, and the analysis of its sequence showed a complete match with the authentic human placental LHRH cDNA. These observations clearly demonstrate that a mRNA for LHRH is expressed in human prostatic cancer cells, and suggest that LHRH or a LHRH like peptide may be produced by these cells. To test the hypothesis whether this material might act as a local growth regulating factor on tumor cell proliferation, LNCaP cells, grown in a steroid-free medium, were treated daily with a potent LHRH antagonist. After 9, 12 and 15 days, the treatment resulted in a significant increase of tumor cell proliferation. These data clearly suggest that the LHRH mRNA expressed in LNCaP cells is possibly translated into LHRH or a LHRH-like peptide which probably functions as a local growth inhibitory factor on prostatic tumor cell proliferation, by acting on LHRH receptors. PMID- 8445039 TI - Parathyroid hormone-related protein (PTHrP) does not regulate 1,25 dihydroxyvitamin D serum levels in hypercalcemia of malignancy. AB - We investigated in humoral hypercalcemia of malignancy whether parathyroid hormone-related protein (PTHrP) elevation causes a rise in 1,25-dihydroxyvitamin D (1,25-(OH)2 D) serum levels. We assessed 41 patients with hypercalcemia of malignancy in a prospective study. There were 19 patients who had serum PTHrP levels in the normal range; 22 patients had elevated serum PTHrP levels. All patients were treated with the bisphosphonate pamidronate resulting in a drop of serum calcium (p < 0.0001) and serum phosphate (p < 0.0023) within 12 days, independent of the group. Parathyroid hormone (PTH) was suppressed at the start of therapy and rose to within the normal range during therapy (p < 0.0001), regardless of the PTHrP levels. PTHrP levels were not influenced by calcium lowering therapy. The serum levels of 1,25-(OH)2 D were either suppressed or in the low normal range at the beginning of the study, without any significant difference between both groups. All patients showed a rise in 1,25-(OH)2 D during bisphosphonate therapy (p < 0.0001), independent of their PTHrP levels. Thus PTHrP did not influence the calcium, phosphate-, or PTH-dependent regulation of 1,25-(OH)2 D during calcium lowering therapy. We conclude, that PTHrP does not stimulate renal 1-hydroxylase activity in humoral hypercalcemia of malignancy. PMID- 8445040 TI - Insulin-like growth factor I inhibits glucose-stimulated insulin secretion but does not impair glucose metabolism in normal humans. AB - The effect of human recombinant insulin-like growth factor I (rhIGF-1) on glucose stimulated insulin secretion was studied in 14 healthy human volunteers. Each subject received a primed-continuous infusion of rhIGF-1 (20 micrograms kg prime, 0.4 micrograms kg-1 min-1) or saline while plasma glucose was raised +2.8 mmol/l (+50 mg/dl) (n = 6) or +7.0 mmol/l (+125 mg/dl) (n = 8) above baseline for 2 h using the hyperglycemic clamp technique. Total IGF-1 levels during the IGF-1 studies increased from 196 +/- 37 to 449 +/- 71 ng/ml. At the +2.8 mmol/l (+50 mg/dl) stimulus, first and second phase C-peptide levels were suppressed during IGF-1 infusion vs control (885 +/- 157 vs 544 +/- 99 pmol/l, p < 0.05 and 1379 +/ 246 vs 832 +/- 130 pmol/l, p < 0.05, respectively), whereas insulin levels were suppressed during the second phase only (215 +/- 43 vs 151 +/- 28 pmol/l, p < 0.05). Despite this, the rate of glucose metabolism was two-fold higher in the IGF-1 infused group (8.0 +/- 0.5 vs 3.5 +/- 0.1 mg kg-1 min-1, p < 0.01). At the higher glucose stimulus +7.0 mmol/l (+125 mg/dl) only second phase C-peptide levels were significantly reduced (1922 +/- 251 vs 1466 +/- 74 pmol/l, p < 0.05). Again, rates of glucose metabolism were higher during IGF-1 infusion (11.8 +/- 1.2 vs 8.9 +/- 0.8 mg kg-1 min-1, p < 0.01). These data suggest that rhIGF-1 inhibits glucose-stimulated insulin secretion in humans, but that this inhibitory effect is partially overcome by increasing the hyperglycemic stimulus. Moreover, despite the decrease in insulin secretion, glucose disposal is accelerated by rhIGF-1. PMID- 8445041 TI - Mechanisms of autoimmunity in type I diabetes. AB - The work presented in this review suggests that in human and murine type I diabetes, defective MHC class I expression on APC is linked to autoimmunity. The defect in self-antigen presentation is present on prediabetic and diabetic APC, and this presumably delivers abnormal or lack of signals to T cells to allow self tolerance. Since most autoimmune diseases have strong genetic linkage to MHC class II region, our recent results additionally demonstrating low MHC class I expression on lymphoid cells in a diversity of autoimmune diseases (hypothyroidism, rheumatoid arthritis, lupus, etc.) suggest that this pathway of abnormal class I presentation of self epitopes may be important for tolerance to many tissue-specific antigens (40). Certainly, the unanswered genetic questions will address the role of the specific genes controlling self-antigen presentation through MHC class I followed by T-cell education to self. PMID- 8445042 TI - Tumor necrosis factor alpha production in schistosomiasis with carcinoma of urinary bladder. AB - Schistosomiasis parasitic infection (Schistosoma haematobium) is associated in some patients with bladder cancer. The production of cytokines such as tumor necrosis factor alpha (TNF alpha) is a key event of inflammation in human infectious disease and malignancy. TNF alpha has not been previously investigated from schistosomiasis infection and bladder malignancy. In this report we demonstrate that serum levels of TNF alpha are highly elevated in patients with schistosomiasis of urinary bladder (SB), schistosomiasis with carcinoma of urinary bladder (SCB), and carcinoma of urinary bladder without schistosomiasis (CB). Purified monocytes from bladder malignancy (SCB and CB) cultured without exogenous stimuli release TNF alpha in the culture supernatants. However, lipopolysaccharides and concanavalin A stimulation of monocytes from these patients produced highly elevated levels of TNF alpha compared with normal controls. The findings that monocytes are the potent producers of TNF alpha in this malignancy may be a key observation implicating these cells in the pathophysiology of this disease. Furthermore, it was shown that serum TNF alpha levels correlated with the clinical staging of disease in both SCB and CB, with higher levels in T3 and T4 advanced-stage patients and low levels in T1 and T2 early-stage patients. These results suggest that monocyte abnormality and serum TNF alpha levels might be one of the factors contributing to the progression of disease. PMID- 8445043 TI - Correlation between soluble serum CD16 (sCD16) levels and disease stage in patients with multiple myeloma. AB - CD16, the type III receptor for IgG, is expressed on neutrophils, natural killer cells, and some T lymphocytes, mast cells, and activated monocytes but not on cells of the B-lymphocyte lineage including plasma cells. It is also produced in a soluble form found in serum. We analyzed sera from 165 multiple-myeloma patients, 29 patients with monoclonal gammopathies of unknown significance, and 20 normal disease-free donors. We found that the level of soluble CD16 was significantly decreased in sera from patients with multiple myeloma compared to sera from healthy and monoclonal gammopathies of unknown significance donors (P = 0.0001). In addition, a stage-dependent decrease in soluble CD16 was observed, with a highly significant difference (P = 0.004) between stage I and stage II+III myeloma patients. The correlation between the myeloma stage and the serum level of soluble CD16, which is related to the host response, was found to be more sensitive than that of beta 2-microglobulin, which reflects the tumor burden. The concomitant evaluation of the serum levels of these two markers allows better staging and therefore has a more precise prognostic value. PMID- 8445044 TI - Suppression of the development of tumoricidal function in gamma interferon treated human peripheral blood monocytes by lipopolysaccharide: the role of cyclooxygenase metabolites. AB - Bacterial lipopolysaccharide (LPS) is generally regarded as one of the most potent macrophage activators. Thus, LPS has been used as an obligatory second signal to stimulate macrophage cytotoxic function against a wide array of bacterial and neoplastic targets. In this study, however, we define conditions under which LPS can suppress the development of cytotoxic function in normal human peripheral blood monocytes. When monocytes were treated with a priming dose of gamma interferon (gamma-INF), followed 18-24 hr later by a triggering dose of LPS, significant cytotoxic function developed. However, when monocytes were treated with even minimal amounts of LPS during priming with interferon, the development of cytotoxic function following stimulation with a second, triggering dose of LPS was virtually abolished. This effect could be produced from 0 to 14 hr following the addition of gamma-INF. The inhibition of monocyte cytotoxicity which was produced by LPS treatment during priming was dose dependent and could not be overcome by modifying either the priming dose of gamma-IFN or the triggering dose of LPS. The suppression was largely overcome, however, by treatment with the cyclooxygenase inhibitor, indomethacin. The possibility that LPS-induced suppression of monocyte cytotoxicity was mediated by products of the cyclooxygenase pathway was supported further in this study by demonstrating that LPS stimulated the production of significant amounts of prostaglandin E2 (PGE2) from monocytes and that this was facilitated by gamma-IFN. In kinetics studies, it appeared that LPS suppression of monocyte activation was correlated temporally with a heightened sensitivity to suppression by exogenously added PGE2, a condition which was reduced greatly by the end of the priming phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8445045 TI - Cytokine profile in systemic lupus erythematosus, rheumatoid arthritis, and other rheumatic diseases. AB - We investigated serum levels of interleukin-6 (IL-6), interferon-gamma (IFN gamma), and tumor necrosis factor alpha (TNF alpha) from patients with systemic lupus erythematosus (SLE) and its various clinical manifestations of disease and from patients with rheumatoid arthritis (RA) and other rheumatic diseases. The serum levels of IL-6 and IFN-gamma were highly elevated from patients with SLE associated with lymphadenopathy (LN) or nephrotic syndrome (NS). On the contrary, the serum levels of TNF alpha were elevated from most patients with SLE associated with thrombocytopenia (TP). However, serum levels of TNF alpha were in the normal range from patients with SLE associated with NS, LN, or central nervous system disease. Of interest, patients with SLE associated with humoral immunodeficiency disorder, hypogammaglobulinemia, had highly elevated levels of serum IL-6. The concanavalin A-stimulated mononuclear cells (MNC) of patients with SLE associated with TP secreted highly elevated levels of TNF alpha compared to other patient groups. We suggest that abnormal production of various cytokines in SLE is an intrinsic defect of MNC and the immune system that may be the key element for a variety of clinical manifestations of this disease. PMID- 8445047 TI - A potential role for costo-chondral grafting in adults with mandibular condylar destruction secondary to rheumatoid arthritis--a case report. AB - Little attention has been directed towards reconstruction of the mandibular condyles in adult patients with rheumatoid arthritis, other than with allogenic implants which are now known to cause serious complications. There is a relatively high incidence of condylar erosion and breakdown in rheumatoid arthritis, often leading to anterior open bite and retrognathia. Costochondral grafting does not appear to have been considered as a logical option for reconstruction, despite its high success rate in many other situations. A case is described of rapid bilateral condylar destruction occurring in a young woman with rheumatoid arthritis, leading to anterior open bite. Reconstruction was undertaken using bilateral costochondral grafts, giving an excellent clinical result which has been maintained over the follow-up period of two-and-a-half years. Radiologically complete healing of severe glenoid fossa erosion has taken place. PMID- 8445048 TI - A modification of the Sanvenero-Rosselli velopharyngoplasty. AB - A modification of the cranially-pedicled velopharyngoplasty is described. It consists of the preparation of two mucosal flaps on the dorsal side of the soft palate. They are pedicled on the velar rim and sutured to the free part of the pharyngeal flap between its origin and the recipient bed. Advantages of the method comprise reliable healing, the breadth of the flap and an improved velopharyngeal occlusion with results which favourably influence speech. PMID- 8445046 TI - Down-regulation of tumor necrosis factor alpha activity by acute ethanol treatment in human peripheral blood monocytes. AB - As the most commonly used drug that can modulate both metabolic and immune pathways, ethanol is evaluated in this report as a regulator of tumor necrosis factor alpha (TNF alpha) production in human peripheral blood monocytes (M phi) in combination with a variety of stimuli. While acute ethanol treatment did not induce TNF alpha in M phi, it was a potent down-regulator of M phi TNF alpha production whether induced by the combination of interferon-gamma plus muramyl dipeptide (MDP) (P < 0.001), lipopolysaccharide (LPS) alone (P < 0.01), or interferon-gamma plus LPS. Down-regulation of M phi TNF alpha by ethanol was dose dependent and statistically significant in the biologically relevant, 25-150 mM, ethanol concentration range. We also demonstrate that these ethanol concentrations did not affect M phi viability. TNF alpha down-regulation by ethanol was most effective when ethanol was administered 4 hr prior to MDP stimulation; however, it was also effective--though to a lesser extent--if it was added at the time of MDP stimulation. Furthermore, ethanol also down-regulated TNF alpha production of the in vivo preactivated M phi of trauma patients, which produce hyperelevated levels of TNF alpha. We have previously shown that the majority of posttrauma elevated M phi TNF alpha is produced by the M phi subpopulation expressing high-affinity type I Fc gamma receptors (Fc gamma RI). When the Fc gamma RI cross-linking-stimulated M phi subpopulation was treated with acute ethanol, TNF alpha production was suppressed again both in in vivo preactivated M phi of trauma patients and in M phi of normal controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8445049 TI - Audiological evaluation of the aural symptoms in temporomandibular joint dysfunction. AB - In this study, audiological assessments of the 57 patients with temporomandibular joint dysfunction and 57 controls were made. The analyses of audiograms, tympanograms and Eustachian tube functions showed no significant differences statistically. A slight increase in compliance peak in 48 female patients suggests that the sound conducting structures of the middle ear could be influenced by the reflex spasm of the tensor tympani muscle to a minor degree. This change does not seem to cause a major dysfunction either in the middle ear or in the Eustachian tube. PMID- 8445050 TI - Congenital fistula with an island of vermilion-epithelium in the paramidline of the upper lip: report of a case. AB - An extremely rare case of a congenital fistula with an island of vermilion epithelium in the paramidline of the upper lip in a 17-year-old male is presented. The fistula was located in the paramidline of the philtrum dimple, and mucoid secretion from the fistula was noted. The fistula's orifice opened in the center of a well-defined, slightly dimpled, round, vermilion-like epithelium just above the vermilion border. The fistulous tract terminated in a cul-de-sac and its end was located near the alveolar process. Fistulectomy was carried out via an extra-oral approach and the epithelial defect was closed using a rotation flap. Histological examination revealed that the fistula was lined by squamous epithelium with sebaceous and mucous glands, and vermilion-like area island consisted of thin keratinized stratified squamous epithelium without skin appendages, the same as the epithelium of the lip vermilion. PMID- 8445051 TI - Laser Doppler monitoring of free microvascular flaps in maxillofacial surgery. AB - In free microvascular flap transplantation, reliable postoperative monitoring is necessary to indicate the necessity for early re-exploration in the event of decreased blood supply. In this study the positive evidence of laser Doppler monitoring of free flaps was investigated in 28 cases. Myocutaneous, osteomyocutaneous and small intestine flaps were measured. The laser Doppler flowmetry values ranged within a wide band and were relative to the different tissues measured, and the patients. It was not possible to define a reliable inferior limit for the various tissues. Only the assessment of the development of the values was interesting. Flaps with high measured laser Doppler flowmetry values were successful, flaps with decreasing values showed problems. The most important tool for the surgeon is his clinical experience, but laser Doppler monitoring in flap transplantation can be helpful to the surgeon. PMID- 8445052 TI - Tumoricidal effect of human PBMC following stimulation with OK-432 and its application for locoregional immunotherapy in head and neck cancer patients. AB - Both cell-mediated and cytokine-mediated antitumor activities were induced in peripheral blood mononuclear cells (PBMC) in short-term culture with streptococcal preparation, OK-432. Kinetic analysis of OK-432-activated killer activity (OKAK) showed that it reached a plateau level much faster (by 48 h of culture) than that detected in PBMC stimulated with recombinant interleukin 2 (rIL-2) (lymphokine-activated killer: LAK). We also found that the tumor growth inhibitory factor (TGIF) activity was produced in the culture supernatant (CSN) of the OK-432-activated PBMC (OK-MC) and the activity synchronously increased with augmentation of OKAK activity. The TGIF activity was rarely found in the CSN of rIL-2-stimulated PBMC. The TGIF activity detected in CSN of OK-MC was further characterized as derived from a cytokine different from interferon gamma (IFN gamma), tumor necrosis factor (TNF), or lymphotoxin (LT) by a neutralization test using monoclonal antibodies to these cytokines. These 48-h-cultured-OK-MC were adoptively transferred (adoptive immunotherapy: AIT) into 19 head and neck cancer patients either alone or in combination with chemotherapy and/or radiation therapy, and their therapeutic effects were examined. AIT was performed by intra arterial or intratumoral administration of OK-MC. There were no significant side effects observed in this treatment. In these patients, approximately 1-10 x 10(7) cells were transferred into the tumor burden. Of the 19 patients, 17 had primary cancer, and in 6 (6/17;35%) of them complete remission (CR) of the tumor was obtained. Partial remission (PR) was attained in 9 of the 17 patients (9/17; 53%), giving the overall response rate of 88%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8445053 TI - Vascular malformations of the jaw bones. Report on nine patients. AB - Nine patients with vascular malformations of the jaw bones, 4 affecting the mandible, 2 affecting both jaws and 3 affecting the maxilla only. Four lesions were of the high flow type and 5 were of low flow type. Our experience in the management of these lesions is presented together with the possible complications. PMID- 8445054 TI - Kaposi's sarcoma. Epidemiology, pathogenesis, histology, clinical spectrum, staging criteria and therapy. AB - The acquired immunodeficiency syndrome (AIDS) epidemic has had a profound impact on our understanding of Kaposi's sarcoma (KS). Epidemiologic features suggest a sexually transmitted cofactor in the pathogenesis of AIDS-associated KS (AIDS KS), and several putative agents have received intense scrutiny. Cell culture studies suggest that the angiogenesis of AIDS-KS is stimulated by both human immunodeficiency virus proteins and growth factors that may be involved in the development and progression of AIDS-KS, thereby providing a rationale for new therapeutic interventions. The dermatologist is uniquely qualified to provide care for the majority of patients with KS, as many patients have cutaneous lesions amendable to local therapy (cryotherapy, intralesional therapy, simple excision). Patients requiring more aggressive local therapy (radiation therapy) or systemic therapies (interferon, chemotherapy) can be easily recognized. Standardized staging criteria provide assistance for determining appropriate local or systemic therapy and for evaluating and comparing responses to new therapies. This article reviews the epidemiology, pathogenesis, histologic features, clinical spectrum, staging criteria, and treatment of KS. PMID- 8445055 TI - Rheumatoid papules: a report on four patients with histopathologic analysis. AB - BACKGROUND: The rheumatoid papule is a recently described skin manifestation of rheumatoid arthritis. OBJECTIVE: Rheumatoid papules from four patients with classic rheumatoid arthritis were examined to determine the origin of this palisading granulomatous reaction. METHODS: Immunofluorescence and electron microscopic studies were performed on biopsy specimens of rheumatoid papules. RESULTS: Leukocytoclastic vasculitis with collagen alteration and lymphohistiocytic infiltration were observed. The immunofluorescence study revealed deposits of immunoglobulins and complement in the vessel walls and in the area of collagen alteration. Electron microscopy revealed epithelioid cell like histiocytes among altered collagen fibers. These cells contained abundant lysosomes and were connected to neighboring cells by well-developed intricate processes. CONCLUSION: Vasculitis is important in the pathogenesis of rheumatoid papules. In patients with rheumatoid papules, systemic evaluation should be performed because these are a manifestation of rheumatoid vasculitis. PMID- 8445056 TI - PUVA keratosis. A clinical and histopathologic entity associated with an increased risk of nonmelanoma skin cancer. AB - BACKGROUND: Various types of hyperkeratotic lesions can be observed in patients with psoriasis treated with PUVA. Clinically it can be difficult to classify them and to differentiate benign from malignant hyperkeratotic lesions. Recently, we introduced the term PUVA keratosis, which we regard as a distinct entity. OBJECTIVE: The purpose of the study was to describe in more detail the clinical and histopathologic features of PUVA keratoses and to investigate a possible relation with nonmelanoma skin cancer. METHODS: A group of 13 psoriasis patients with PUVA keratoses was studied and compared with 247 psoriasis patients without these keratoses, who had also received long-term therapy with PUVA. RESULTS: The presence of PUVA keratoses was associated with an increased risk of nonmelanoma skin cancer. The estimated relative risk for skin cancer in patients with PUVA keratoses, adjusted for age, sex, and UVA dose, as compared with psoriasis patients without these keratoses, who had also received long-term PUVA treatment, was 6.5 (95% confidence interval, 1.3 to 32.1). Squamous cell carcinomas contributed the most to this increased risk. CONCLUSION: PUVA keratoses are associated with an increased risk of nonmelanoma skin cancer. Therefore careful clinical follow-up of psoriasis patients with PUVA keratoses is necessary, and cessation of PUVA treatment should be considered. PMID- 8445057 TI - Planimetric rate of healing in venous ulcers of the leg treated with pressure bandage and hydrocolloid dressing. AB - BACKGROUND: Venous leg ulcers are a common cause of morbidity, but few predictive parameters exist that can be used to follow their progress. OBJECTIVE: We investigated the use of healing rate as a useful parameter in the treatment of venous ulceration. METHODS: Twenty-seven venous ulcers being treated with a standard regimen were evaluated. We calculated the initial (4-week) and overall healing rates using the Gilman method (delta A/p). RESULTS: The average initial healing rate for all ulcers combined, the healed group, and the nonhealing group was 0.069, 0.087, and -0.005 cm/wk, respectively. Similarly, the average overall healing rate for all ulcers combined, the healed group, and the nonhealing group was 0.062, 0.089, and -0.043 cm/wk, respectively. CONCLUSION: The initial healing rate (delta A/p(0-4)) may be an appropriate end point for clinical investigations comparing therapies for the treatment of chronic venous leg ulcers. PMID- 8445058 TI - The annual cost of psoriasis. AB - BACKGROUND: The need for comparative cost figures for psoriasis therapy has become increasingly important. OBJECTIVE: Our purpose was to compare the yearly costs of various psoriasis treatments. METHODS: Ten patients were selected for each treatment modality and the average total cost per year, per patient was evaluated. RESULTS: All treatments evaluated were cheaper than inpatient therapy, with Goeckerman treatment in the day-care setting the most expensive and hydroxyurea the cheapest. Cyclosporine, which was used for comparison, was at least twice as expensive as all the other treatments except for Goeckerman treatment in the day-care setting, compared with which it was about 70% more expensive. CONCLUSION: No single treatment appears to be universally superior to others. In considering specific treatment for psoriasis, cost analyses, including appropriate laboratory and other specialized evaluations, must be taken into account. With use of these data, practitioners and health care organizations may be better able to select appropriate therapy. PMID- 8445059 TI - Immunophenotypic and genotypic analysis in cutaneous lymphoid hyperplasias. AB - BACKGROUND: The clinical utility of immunophenotyping and Southern blot analysis in the evaluation of patients with cutaneous lymphoid hyperplasia (CLH) is controversial. OBJECTIVE: Our purpose was to determine whether adjunctive immunophenotyping and Southern blot analysis are of diagnostic and prognostic value in patients with CLH. METHODS: Immunophenotyping was performed on skin biopsy specimens from 26 patients with a routine histologic diagnosis of CLH. Southern blot analysis for immunoglobulin (Ig) gene rearrangements was done on 13 of 26 cases. RESULTS: Twenty-four of 26 patients had polyclonal CLH on immunophenotyping: 2 of 26 had monoclonal lymphoma. Two of 11 patients with polyclonal CLH studied by Southern blot analysis had clonal Ig gene rearrangements. In both, lymphoma developed within 1 to 6 years; comparison of CLH and malignant lymphoma demonstrated overlapping and different clonal bands. Two additional patients with polyclonal CLH developed lymphoma. No clonal gene rearrangements were detected in the CLH or lymphoma from one; the other was not studied. CONCLUSION: Immunophenotyping will identify some patients with lymphoma with nondiagnostic histologic features. Southern blot analysis will predict some patients with polyclonal CLH in whom malignant lymphoma will develop and who may benefit from definitive therapy. PMID- 8445060 TI - The Demodex mite population in rosacea. AB - BACKGROUND: The cause of rosacea is unknown; among other factors a causative role has been postulated for the hair follicle mites Demodex folliculorum and Demodex brevis. OBJECTIVE: Our purpose was to compare the population density of Demodex mites in facial skin of defined categories of patients with rosacea with control subjects. We also assessed the impact of tetracycline therapy on the mite population. METHODS: The population density and distribution of Demodex mites were studied in the facial skin of 42 patients with rosacea and 42 age- and sex matched control subjects. Mites were counted in measured skin surface biopsy specimens obtained from six standard facial sites with cyanoacrylate glue. RESULTS: The mean mite count was 49.8 (range 2 to 158) in patients with rosacea and 10.8 (range up to 97) in control subjects (p < 0.001); the highest density of mites was found on the cheeks. A statistically significant increase in mites was found in all subgroups of rosacea, being most marked in those with steroid induced rosacea. Mite counts in patients with rosacea before and after a 1-month course of oral tetracycline showed no significant difference. CONCLUSION: Increased mites may play a part in the pathogenesis of rosacea by provoking inflammatory or allergic reactions, by mechanical blockage of follicles, or by acting as vectors for microorganisms. PMID- 8445061 TI - AIDS-associated Kaposi's sarcoma in Romanian children. AB - BACKGROUND: Kaposi's sarcoma (KS) is commonly associated with the acquired immunodeficiency syndrome (AIDS) in adults. Little is known regarding its occurrence in children. OBJECTIVE: Our purpose was to report the clinical and epidemiologic characteristics of KS in three Romanian children with AIDS and to compare them with previously reported AIDS-associated KS in children. METHODS: This was a clinicopathologic study and computer-based literature review. RESULTS: All three Romanian children had skin involvement; two had involvement of lymph nodes and internal organs. All had acquired human immunodeficiency virus (HIV) infection postnatally. Including these children, 33 cases of AIDS-associated KS in children have been reported. Thirteen of 30 evaluable patients had acquired HIV infection postnatally; nine of these children (69%) had cutaneous involvement by KS. A perinatal route of transmission was present in the remaining 17 cases; only two of these children (12%) with KS had cutaneous involvement. No case was noted in which intravenous drug use was the sole parental HIV risk factor. CONCLUSION: The data support the contention that KS is caused by a second infectious agent prevalent only in certain HIV-infected populations. Children of parents in high-risk groups for KS and children who acquire HIV via contaminated blood or blood products are at highest risk for KS. The route of acquisition of HIV infection may also be associated with different clinical manifestations of KS in children. PMID- 8445062 TI - An approach to the treatment of moderate to severe psoriasis with rotational therapy. AB - BACKGROUND: There are four standard approaches for treating moderate to severe psoriasis: UVB plus tar, PUVA, methotrexate, and etretinate. Although patients with psoriasis receive these therapies for many years, there is no commonly accepted approach for the initial and subsequent selection of the alternatives. OBJECTIVE: Our purpose was to develop a theoretical and practical basis for using these treatments that will minimize the risks of their long-term toxicities and prolong their safe long-term use. METHODS: A review of the published side effects of the treatments and cumulative clinical experience are used to develop an approach for the treatment of severe psoriasis. RESULTS: It is proposed that patients receive each form of therapy for 1 to 2 years and then switch to the next form of treatment. By rotating each of the three or four treatments at these time intervals, it may well be 4 or 5 years before needing to return to the first therapy, thereby minimizing cumulative toxicity by long periods off each treatment. CONCLUSION: Rotation of available therapies for moderate to severe psoriasis may minimize long-term toxicity and allow effective treatments to be maintained for many years. PMID- 8445063 TI - Plasma levels of 8-methoxypsoralen after topical paint PUVA. AB - BACKGROUND: Topical PUVA therapy has become a useful alternative for patients who cannot tolerate the systemic side effects of nausea and headache or are concerned about the ophthalmologic risk associated with oral PUVA therapy. However, there is no study to date on the systemic absorption of psoralen after the localized application of topical paint PUVA. OBJECTIVE: This study was designed to assess the plasma level of 8-methoxypsoralen (8-MOP) after paint PUVA therapy for patients with palmoplantar psoriasis or eczema. METHODS: Reverse-phase high pressure liquid chromatography was used to determine 8-MOP plasma levels in eight patients with palmoplantar psoriasis and two with eczema. Three patients receiving oral PUVA therapy served as the control group. RESULTS: Plasma levels of 8-MOP taken 1, 6, and 24 hours after topical PUVA treatments of patients with palmoplantar psoriasis were undetectable. One patient with hand eczema consistently had detectable 8-MOP levels 1 hour after topical PUVA treatments. CONCLUSION: This report indicates that there is minimal, if any, systemic absorption of 8-MOP after topical PUVA treatment of patients with palmoplantar psoriasis. PMID- 8445064 TI - Treatment of gastrointestinal symptoms associated with methotrexate therapy for psoriasis. AB - BACKGROUND: The conventional treatments for gastrointestinal symptoms associated with methotrexate therapy for psoriasis are unsatisfactory. OBJECTIVE: Our purpose was to determine the frequency, severity, and dose-relationship of gastrointestinal symptoms induced by methotrexate therapy for psoriasis and the response to folate supplementation. METHODS: Seventy-eight patients with psoriasis receiving low-dose, once-weekly oral methotrexate therapy were studied for the development of gastrointestinal symptoms. The effect of supplementation with folic acid, 5 mg daily, on gastrointestinal symptoms was examined. RESULTS: Gastrointestinal symptoms occurred in 32% of patients; nausea accounted for 80% of symptoms. The onset and severity of symptoms were related to the weekly dose of methotrexate but not to the cumulative dose or to the duration of methotrexate therapy. The symptoms were eliminated by folate supplementation; this did not interfere with the therapeutic effect of methotrexate. CONCLUSION: Gastrointestinal symptoms occur frequently with methotrexate therapy for psoriasis and can be adequately controlled with folate supplementation, apparently without compromising the therapeutic efficacy of methotrexate. PMID- 8445065 TI - Histologic features of foreign body reactions in patients infected with human immunodeficiency virus type 1. The Military Medical Consortium for Applied Retroviral Research. AB - BACKGROUND: Within a large population of patients seropositive for human immunodeficiency virus type 1 (HIV-1), seven had biopsy specimens that showed foreign body reactions with histologic features different from those seen in non HIV-1-positive patients. OBJECTIVE: These cases were reviewed to determine whether there was a specific pattern of response to foreign bodies in HIV-1 infection and whether this pattern was related to the stage of disease. METHODS: Biopsy specimens were reviewed to identify ruptured epidermal cysts. These were studied in routine hematoxylin-and-eosin-stained sections and with immunohistochemical stains to characterize the inflammatory infiltrate. RESULTS: The lesions in HIV-1-infected patients contained abundant macrophages with evidence of decreased function and a lack of giant cells. CONCLUSION: These histologic features suggest an early functional deficit before there is a significant decrease in the number of T4 lymphocytes. PMID- 8445066 TI - Collagen-vascular disease: An update. PMID- 8445067 TI - Multiple skin tumors on light-exposed areas during long-term treatment with hydroxyurea. PMID- 8445068 TI - An aggressive case of classic Kaposi's sarcoma. PMID- 8445069 TI - Polymyositis and chronic graft-versus-host disease: efficacy of intravenous gammaglobulin. PMID- 8445070 TI - Basal cell carcinoma arising in a fibroepithelial polyp. PMID- 8445071 TI - Cutaneous leishmaniasis: an unusual case with atypical recurrence. PMID- 8445072 TI - Pigmented epithelioid cell nevus: a variant of Spitz nevus? PMID- 8445073 TI - Acquired zinc deficiency in a premature breast-fed infant. PMID- 8445074 TI - Acanthosis nigricans-like lesions after local application of fusidic acid. PMID- 8445075 TI - Successful treatment of dermatitis herpetiformis with tetracycline and nicotinamide in a patient unable to tolerate dapsone. PMID- 8445076 TI - Biblical leprosy: an anachronism whose time has come. AB - Although there is a growing consensus that biblical leprosy was indeed not Hansen's disease, there has been no agreement as to the disease or diseases described in the Bible. Biblical scholars have recently provided valuable insights regarding the interpretation of the original text on the cutaneous diseases described in Leviticus, chapter 13. It is suggested by the author that no particular cutaneous disease was meant to be implicated. Rather the passages were written to exonerate persons whose only "sin" was to have an obvious cutaneous disorder. PMID- 8445077 TI - Efficacy of cyclophosphamide in toxic epidermal necrolysis. PMID- 8445078 TI - Yes, systemic nickel is probably important! PMID- 8445079 TI - Acquired hairy pinnae in a patient infected with the human immunodeficiency virus. PMID- 8445080 TI - Diagnostic utility of magnetic resonance imaging in malignant melanoma. PMID- 8445081 TI - Why do nurses participate in continuing education? A meta-analysis. AB - In order to explain why nurses participate in continuing education, a meta analysis of 22 studies was conducted. All of the studies examined the relationship between several independent variables from the Urbano and Jahns' model and nurses' participation in continuing nursing education (CNE). This study supported the Urbano and Jahns' proposition that motivational orientation influences participation, while other factors, such as demographics and educational opportunity, may mediate the degree of that influence. PMID- 8445082 TI - Sexual harassment: perspectives from the past, present practice, policy, and prevention. AB - During the times of Florence Nightingale, elements of sexual harassment were evident and were addressed in her writings. The more recent Anita Hill-Clarence Thomas judicial hearings brought more attention to the issue. It is imperative that hospitals and their staff development departments have a clear understanding of what constitutes sexual harassment so that effective policies can be implemented. Preventive training can be implemented to avoid absenteeism, staff turnover, lost productivity, decreased quality of patient care, and exorbitant legal costs. PMID- 8445083 TI - Marketing university-based continuing education programs. AB - It is important for nursing educators engaged in the highly competitive business of continuing education (CE) to understand marketing educational programs. There has been hesitancy in using the word "marketing" in the educational setting; and it has only been recently that marketing directors have been hired at some universities to promote their educational programs. The author describes how marketing techniques and business strategies are used in educational settings, especially for marketing CE programs. PMID- 8445084 TI - Institute for Nursing Excellence: a retention model. AB - In 1989, the General Assembly funded initiatives for the recruitment and retention of nurses, including two pilot "Institutes for Nursing Excellence" designed to develop, recognize, and reward excellent staff nurses. The Wake Area Health Education Center (AHEC) implemented the pilot projects. In 1991, additional funding was obtained to replicate the pilot projects. The grant was awarded to the Wake AHEC from the General Assembly, through the newly established Center for Nursing. This cooperative effort between the legislature and nursing is considered a model of its kind in this state and possibly the nation. The purpose of the Institute was to develop mentoring, role-modeling, change, and lifelong learning skills in an atmosphere of renewal, rejuvenation, and trust. PMID- 8445085 TI - An orientation plan for hospital-based case managers. AB - The key to a successful case management program is the case manager. This article is a description of a six-week orientation program provided for new case managers at St. Peter's Medical Center in New Jersey. The principal components of the program are basic content modules, addressing individual learning needs, specific teaching strategies, and a self-paced approach. PMID- 8445086 TI - Structured controversy versus lecture on nursing students' beliefs about and attitude toward providing care for persons with AIDS. AB - Like many nurses in clinical practice, a small sample of RN-to-BSN nursing students reported their negative attitude toward providing care for persons with AIDS (PWA). Structured controversy is an interactive educational approach that may promote positive attitudes. This experimental study compared the effectiveness of structured controversy with lecture on BSN students' beliefs about and attitude toward providing care for PWA. A questionnaire, based on Ajzen and Fishbein's (1980) theory of reasoned action, was completed by 51 BSN students following an AIDS class session, and by nursing faculty. When compared with students who had listened to the lecture, students who had participated in structured controversy were more positive in general, and were significantly more positive on individual attitude and belief items. Faculty perceptions of these nursing students' beliefs and attitudes were less positive than the students' actual beliefs and attitudes. PMID- 8445087 TI - Informational needs and preferred time to receive information for phase II cardiac rehabilitation patients: what CE instructors need to know. AB - The purpose of this study was to determine the perceived importance of selected informational needs of cardiac rehabilitation patients and to determine the best time interval to provide this information. The findings of this study support previous studies showing that cardiac rehabilitation patients perceive all information as important and, as such, it is essential that patients and families receive daily information. Information should be provided simply and in nontechnical terms. With a trend toward shorter hospital stays, this study challenges the health care team to provide necessary information in less time. Implications for staff development are described. PMID- 8445088 TI - CE update for Alabama. PMID- 8445089 TI - How to outsmart "Murphy". AB - Critical thinking and creativity are two of the many skills that nursing educators try to develop in their students. Assessing a problem, planning possible solutions, and then creatively using the resources available to implement the solution take practice. As nurse educators, we must not become "rusty" in these highly valued skills. The article is this author's humorous account of using these skills. PMID- 8445090 TI - Electrophoretic comparisons of lactoferrin from bovine mammary secretions, milk neutrophils, and human milk. AB - Lactoferrin and Ig are the major glycosylated proteins in whey preparations from colostrum, milk, nonlactating bovine mammary secretions, and milk collected after intramammary endotoxin challenge. Lactoferrin was isolated from these sources and from bovine mammary tissue (nonlactating) and bovine milk neutrophils. Molecular weight forms of isolated lactoferrins were separated by SDS-PAGE. Apparent molecular weight forms of lactoferrin (approximately 83 and 87 kDa) did not differ among lactoferrins isolated from mammary secretions or from mammary tissue, but lactoferrin isolated from milk neutrophils migrated as different molecular weight bands in the gels (approximately 87 and 91 kDa). Human milk lactoferrin also separated as two distinct bands in the gels. All forms of lactoferrin were glycosylated. Differences were distinct in the glycosylation pattern of lactoferrins from human milk, bovine nonlactating mammary secretion, and bovine milk neutrophils. Enzymatic deglycosylation of lactoferrins from those sources resulted in migration of each as a single band (approximately 77 kDa). Apparent molecular weight forms of lactoferrin observed by separation by SDS-PAGE are not the result of genetic variance or differential glycosylation at different stages of mammary gland function. Nevertheless, the forms of lactoferrin result from the presence of glycans on the protein. PMID- 8445091 TI - Production of ultrafiltered skim milk retentate powder. 1. Composition and physical properties. AB - Raw skim milk retentate with 20% solids produced by UF was subjected to different heat treatments and pH adjustments prior to spray-drying. The heat treatments were 65 degrees C for 30 min, 75 degrees C for 28 s, and 85 degrees C for 28 s. pH was adjusted to 6.4, 6.7, and 7.0. Retentate powders were analyzed for moisture, protein, lactose, fat, ash, titratable acidity, and pH. Physical property determinations included solubility index, dispersibility, viscosity, scorched particles, poured density, packed density, and water absorption isotherm. No interaction effects of heat treatment and pH adjustment were observed. pH adjustments affected ash content and solution viscosity. Heat treatment affected solubility and poured density. pH adjustments and heat treatment had only minor effects on the measured properties. PMID- 8445092 TI - Properties of [Ca2+ + Mg2+]-adenosine triphosphatases in the Golgi apparatus and microsomes of the lactating mammary glands of cows. AB - The [Ca2+ + Mg2+]-ATPase activity of bovine lactating mammary gland is associated with membranes. This study compares the ATPase activity in microsomal membranes to that of the Golgi apparatus. The enzyme activity in both fractions hydrolyzed Ca(2+)-ATP and Mg(2+)-ATP. The ATPase activities were inhibited by p chloromercuribenzoate, indicating the involvement of a sulfhydryl group for activity. Although calmodulin had no effect on the ATPase activities of the two fractions, calmodulin antagonists (chlorpromazine, fluphenazine, and trifluoperazine) were inhibitory. Strong inhibitors of the ATPase activities were vanadate, dicyclohexyl-carbodiimide, La3+, and Zn2+. There were some differences in the activities from two membrane fractions. Although both fractions could hydrolyze all of the triphosphonucleotides, cytidine-5'-triphosphate and uridine 5'-triphosphate were poor substrates for the Golgi enzyme. Detergents diminished the activity of the microsomal enzyme to a much greater extent than the ATPase of the Golgi apparatus. Thus, the intact membrane may be more critical to microsomal activity. The role of these enzymes in Ca2+ accumulation in milk is discussed. PMID- 8445093 TI - Vitamin E as an adjuvant in an Escherichia coli J5 vaccine. AB - Vitamin E was tested as an adjuvant in an Escherichia coli (O111:B4) J5 vaccine. Twenty cows were assigned to five groups of 4 cows. Cows in four groups were vaccinated with an E. coli J5 bacterin containing 5 ml of 10(9) boiled cells/ml. Vaccinations were at drying off, 30 d after drying off, and within 48 h after calving. Vaccine adjuvants differed among groups. The four treatment adjuvants were 5 ml of Freund's incomplete adjuvant, 5 ml of vitamin E, 2.5 ml of Freund's plus 2.5 ml of vitamin E, and 5 ml of PBS. Cows in the fifth group were unimmunized controls. A front mammary quarter of each cow was challenged by infusion of 10 micrograms of E. coli J5 lipopolysaccharide approximately 4 wk into lactation. Vitamin E alone enhanced serum IgM titers but had no effect on milk IgM or serum and milk IgG titers. The mixture of Freund's plus vitamin E resulted in peak IgG titers in serum and milk comparable with that of Freund's alone. Persistency of IgG titers in cows immunized with the Freund's plus vitamin E mixture was greater than the persistency of titers for cows immunized with the vaccine containing Freund's alone as the adjuvant. The mixture of Freund's plus vitamin E had a synergistic effect in reducing severity of systemic clinical signs. PMID- 8445094 TI - Serum concentrations of copper, iron, and zinc during Escherichia coli-induced mastitis. AB - Six Holstein cows were intracisternally challenged with 50 cfu of Escherichia coli to induce acute mastitis. Clinical status, milk concentrations of bacteria, and serum albumin concentration were determined to monitor the progress and severity of infection for 72 h after bacterial challenge. Blood samples were also collected throughout infection to determine serum concentrations of Zn, Fe, and Cu. Experimental E. coli mastitis resulted in mean serum concentrations of Zn, Fe, and Cu of 28, 35, and 52% of prechallenge concentrations. These decreases first occurred 4 to 12 h after peak bacterial concentration in milk. Changes in serum trace elements may occur too late in the pathogenesis of infection to decrease peak bacterial numbers in milk. However, mediation of infection and inflammation may occur in later stages of the infection process. PMID- 8445095 TI - Endotoxemia in dairy cattle: role of eicosanoids in reticulorumen stasis. AB - The role of arachidonic acid metabolites in the forestomach stasis induced by Escherichia coli endotoxin was evaluated. Six adult Holstein cows received saline solution; endotoxin at 1, 10, and 100 ng/kg of body weight; flunixin meglumine at 1.1 mg/kg of body weight; and flunixin meglumine at 1.1 mg/kg plus endotoxin at 100 ng/kg. The frequency of reticulorumen contractions, mental attitude, body temperature, respiratory rate, heart rate, and plasma concentration of prostaglandin E2, prostacyclin, and thromboxane were evaluated. Administration of saline solution and endotoxin at 1 ng/kg had no significant effects. Administration of endotoxin at 10 ng/kg did not cause significant clinical effects or alter reticulorumen contractions but enhanced synthesis of thromboxane. Administration of endotoxin at 100 ng/kg caused mild clinical signs of stasis, reduced the frequency of reticulorumen contractions, and enhanced synthesis of thromboxane and prostacyclin. Reticulorumen stasis was not accompanied by an increase in the plasma concentration of prostaglandin E2. Flunixin meglumine abolished endotoxin-induced reticulorumen stasis, tachycardia, and synthesis of arachidonic acid metabolites. Reticulorumen stasis during bovine endotoxemia is caused either by enhanced synthesis of an arachidonic acid metabolite other than prostaglandin E2 or by local synthesis of prostaglandin E2. PMID- 8445096 TI - Parthenogenetic activation of in vitro matured bovine oocytes. AB - Bovine germinal vesicle oocytes were collected from 2- to 4-mm follicles. Oocytes were matured in medium 199 containing 10% bovine follicular fluid, FSH, and estradiol. Matured oocytes were cocultured for 2 to 24 h with dead bovine sperm in either Tyrode's medium without albumin or with 40% follicular fluid. After removal of sperm, oocytes were cultured an additional 48 to 72 h in synthetic oviduct fluid or medium 199 containing 10% follicular fluid without hormones. Oocyte activation rates (pronucleus to 8 cells), after exposure to dead sperm for 2, 4, 6, 12, or 24 h, in protein-free Tyrode's medium before embryo culture in synthetic oviductal fluid were 11, 17, 41, and 41%. Activation rates were decreased to 3, 9, 8, 27, and 34% for these same times by the addition of estrual follicular fluid to the protein-free Tyrode's medium. Substitution of bovine serum albumin for follicular fluid in the Tyrode's medium resulted in 47% oocyte activation. Activation depended on time and composition of media, occurred with high frequency with matured bovine oocytes under common in vitro culture conditions, and decreased in the presence of bovine follicular fluid. Therefore, because cleavage is not a sufficient measure of embryo quality, parthenogenetic controls must be run. PMID- 8445097 TI - Estrous and endocrine responses of lactating Holsteins to forced ventilation during summer. AB - Fourteen lactating and cycling Holsteins in each of two summers were assigned randomly to pens in a free-stall barn either with or without overhead fans to study the effect of fan cooling on certain endocrine and behavioral responses during the estrous cycle. After an adjustment period of 8 d in the first summer and 21 d in the second summer, jugular cannulas were inserted, and 25 mg of PGF2 alpha were injected. After injection, blood samples were collected frequently for 84 h in the first summer and 88 h in the second summer, followed by collection three times weekly for 3 wk thereafter each summer. Rectal temperatures were lower in the group cooled by fans than in the control group each summer. Luteal progesterone secretion tended to be greater in the fan group each summer; area under the luteal phase curve was significantly higher than for controls during the second summer. There was tendency for more preovulatory surges of LH and higher estrous responses rates in the fan group during the second summer. Thus, fan cooling of lactating dairy cows for several weeks before anticipated breeding provides potential for more efficient reproductive performance during the summer. PMID- 8445098 TI - Effect of copper status on luteinizing hormone secretion in dairy steers. AB - Two experiments were conducted to examine the effects of Cu status on neuroendocrine regulation of LH secretion in dairy steers. In Experiment 1, 18 Holstein steers were assigned randomly to treatment groups in a completely randomized design. Treatments consisted of basal diet alone (control) or supplemented with 5 ppm of Mo or with 20 ppm of Cu. At 8 and 16 wk, Cu concentrations in liver were higher in the group receiving Cu and lower in the group receiving Mo than in the control. Pulse frequencies of LH were not affected by any treatment. Serum LH concentration at 16 wk tended to be lower in the group receiving Mo than in either the control or the group receiving Cu. The ability of the pituitary gland to release LH in response to GnRH was not affected at 17 wk. Concentrations of LH in the pituitary glands were lower in the group receiving Mo than in that receiving Cu or in the controls. No differences in Cu or Mo concentrations were observed in pituitary, median eminence, or hypothalamic tissues. In Experiment 2, 12 Holstein steers were assigned to treatment groups receiving the basal diet supplemented with either 20 ppm or Cu or with 10 ppm of Mo. Spontaneous and GnRH-induced secretion of LH were not influenced by treatments after 8 mo of experiment. Reduction in Cu status has little effect on the endogenous secretion of LH in dairy steers. PMID- 8445099 TI - Effects of treatment of dairy cows with recombinant bovine somatotropin over three or four lactations. AB - Jersey, Dutch Red and White, and Friesian cows were subcutaneously injected with 640 mg of recombinant bST at 28-d intervals from 87 to 115 d after calving through four successive lactations. A TMR (6.72 MJ of NEL) and 168 g of CP/kg of DM) was fed for ad libitum consumption. The bST effects per day were 3.3 kg for milk yield, 189 g for fat yield, 109 g for protein yield, 157 g for lactose yield, 4 MJ of NEL for feed intake, and -4 kg for body weight. Responses in blood parameters measured 7 d after injection were -.007 mmol/L for glucose, -1.3 mg of N/100 ml for urea, 221 mumol/L for 3-hydroxybutyrate, 59 mumol/L for NEFA, 65 ng/L for insulin, 2.8 micrograms/L for thyroxine, and 26.7 micrograms/L for somatotropin. Somatic cell count in milk was 75,000 cells/ml higher in treated cows. Concentrations of NEFA, Ca, Mg, and phosphorus were unaffected. Repeatability of the maximum response in milk yield after bST treatment was low: .2 within and .5 between lactations. Cows treated in the previous lactation had slightly more retained placentas, and birth weight of their calves was 2 kg less. No differences were observed between treated and control cows in disease incidence. Six treated cows were culled in third and fourth lactations. No indications for tissue damage, inflammation, or stress after bST injections were detected. PMID- 8445100 TI - Diurnal variation of rumen ammonia, serum urea, and milk urea in dairy cows at high and low yields. AB - Milk urea content as an indicator of nutritional status may be a useful tool if major sources of variation are considered. Blood and milk samples were collected frequently during 16 to 19 h from four Holstein cows to study diurnal variation of urea content. Corn silage, alfalfa hay, and concentrates were fed. Rumen ammonia, VFA, and pH were measured in three of the cows. A clear serum urea peak, 70 to 85% higher than the lowest concentration, was observed in the higher yielding cows. The serum urea peak occurred 1.5 to 2.0 h after the rumen ammonia peak. Urea in milk equilibrated with serum with a time lag of 1 to 2 h when the rate of change in serum was .5 to 1.0 mM/h. At this rate, the average difference between serum and milk urea content was .8 mM. Urea in total milk tended to be more closely correlated to serum than samples from the gland cistern, but deviations were minor. Our results indicate a relatively rapid equilibration between blood serum and milk urea, also in the gland cistern. Equilibration may be explained by diffusion of urea along the mammary ducts and through the mucosa in the alveoli. If urea is to be used as an indicator of nutritional status, diurnal variations of serum and milk urea should be considered; time of sampling versus time of feeding is crucial. A small milk sample from a healthy quarter may give information on urea that is as good as that of a sample from regular milking. PMID- 8445101 TI - Effects of supplemental protein source on intraruminal fermentation, protein degradation, and amino acid absorption. AB - Cannulated steers were used to determine the effects of supplemental soybean meal, heated soybean meal, fish meal, and a combination of fish meal, heated soybean meal, and corn gluten meal on intraruminal protein degradation and absorption of AA from the small intestine. Organic matter digestion in the reticulo-rumen was greater in steers fed diets supplemented with soybean meal, but whole tract digestibility was not affected by protein source. Total and bacterial CP flows to the abomasum were lower in steers fed diets supplemented with fish meal than in steers fed diets supplemented with heated soybean meal or the combination supplement. Dietary CP flow was 33.5% higher in steers fed diets supplemented with heated soybean meal than in steers fed diets supplemented with soybean meal, fish meal, or the combination supplement. Less essential and nonessential AA flowed to the abomasum and were absorbed from the small intestine of steers receiving diets supplemented with soybean meal. Digestibility of small intestine AA was 21.9% lower in steers receiving the soybean meal treatment. Abomasal flows of Met and Thr and absorption of Lys, Met, and Thr were increased in steers fed diets containing heated soybean meal, fish meal, and the combination supplement. These results suggest that the supply of AA deficient in microbial CP (Lys, Met, and Thr) can be increased and that absorbed AA balance can be changed markedly by selection of rumen escape protein supplements. PMID- 8445102 TI - In vitro and in vivo ruminal and physiological responses to endophyte-infected tall fescue. AB - Relationships between alkaloid compounds in endophyte-infected tall fescue and ruminal metabolism were studied in two experiments. In the first experiment, different combinations of the pyrrolizidine alkaloids, N-formyl and N-acetyl loline, were incubated with ruminal fluid for 0, 24, or 48 h. Rate of disappearance of N-formyl and N-acetyl loline increased over time. After 48 h, disappearance of N-formyl loline and combinations of N-formyl and N-acetyl loline was greater than N-acetyl loline. Significant amounts of N-formyl and N-acetyl loline were metabolized and converted to loline. In the second experiment, abomasally cannulated sheep were fed increasing amounts of endophyte-infected feed to compare diet digestibility, alkaloid metabolism, and physiological responses. Total tract DM digestibility was greatest for the endophyte-free diet, as were ruminal and total tract ADF, ruminal NDF, and total tract CP digestibilities. N-Formyl and N-acetyl loline recoveries averaged 5% from abomasal contents and 0% in feces. Sixty-eight percent of the pyrrolizidine alkaloids recovered in abomasal contents had been metabolizable to loline. Ergot alkaloids administered in the diet were recovered (50 to 60%) in the abomasal contents, but recovery was only 5% in fecal collections. No significant differences occurred in the physiological parameters measured. Results indicate that response to endophyte-infected tall fescue may be influenced by ruminal metabolism. PMID- 8445103 TI - Effects of beta-carotene and alpha-tocopherol on rumen bacteria in the utilization of long-chain fatty acids and cellulose. AB - Addition of safflower oil to a growth medium depressed the growth of mixed rumen bacteria above 200 mg/L and did not significantly increase bacteria, even at lower concentrations. However, when 10 mg/L of beta-carotene were added to 50 to 100 mg/L of safflower oil, bacterial growth was significantly increased. When more than 200 mg/L of safflower oil were present, beta-carotene markedly restored the growth capacity. alpha-Tocopherol was more effective than beta-carotene, although it inhibited growth at high concentrations. The combination of beta carotene and alpha-tocopherol (each 5 mg/L) exerted partially additive effects. beta-Carotene plus alpha-tocopherol enhanced bacterial cell yield in the presence of safflower oil, caprate, stearate, or linoleate, suggesting that beta-carotene and alpha-tocopherol increase the utilization of fatty acids. beta-Carotene plus alpha-tocopherol also stimulated cellulose digestion in the presence of 100 mg/L of safflower oil, evidently through the increased growth of cellulolytic bacteria. PMID- 8445104 TI - Treatment of porokeratosis of Mibelli with CO2 laser vaporization versus surgical excision with split-thickness skin graft. A comparison. AB - BACKGROUND: Porokeratosis of Mibelli has been treated with many topical surgical modalities in the past, including cold steel surgical excision and CO2 laser excision. We report a patient with an 8 x 10 cm2 plaque of porokeratosis on the dorsum of his hand, fingers, and web spaces. OBJECTIVE: To compare the treatment results of CO2 laser vaporization versus cold steel surgical excision with split thickness skin graft placement. METHOD: The portions of the lesion overlying the metacarpophalangeal joints, fingers, and web spaces were treated with CO2 laser vaporization. The remainder of the lesion covering the dorsum of the hand was excised with cold steel, followed by placement of a split-thickness skin graft over that area. RESULTS: The portion of the porokeratosis lesion treated with CO2 vaporization healed with results cosmetically and functionally superior to the grafted area. CONCLUSION: Carbon dioxide laser vaporization, a more superficial treatment modality than CO2 laser excision, should be the preferred treatment modality for porokeratosis lesions. PMID- 8445105 TI - Hemangioma-associated rhinophyma. Report of a case with successful treatment using carbon dioxide laser surgery. AB - BACKGROUND: Rosacea is a disorder characterized by erythematous papules, pustules, and telangiectases involving the nose, chin, cheeks, and forehead that may progress to rhinophyma. Although the etiology of rosacea remains unclear, a common theme in pathogenesis is vasodilation. Rosacea has been associated with both idiopathic flushing as well as that induced secondarily. OBJECTIVE: To report clinical and histologic features of rhinophyma that developed in association with a longstanding cavernous hemangioma. RESULT: The patient is a 57 year-old Hispanic man with a congenital port-wine stain that had developed into a nodular, cavernous hemangioma over the course of years. Clinically, in the site of the angioma there was marked soft-tissue overgrowth with sebaceous hyperplasia. These changes were confined to the angiomatosis areas and were sharply demarcated from the surrounding normal skin. Histologically, there was marked fibroplasia; numerous small cysts, some with focal rupture and inflammation; dilated follicular ostia; and prominent sebaceous gland hyperplasia in addition to numerous ectatic blood vessels, which were a component of the hemangioma. In contrast, normal-appearing skin adjacent to this site revealed only normal sebaceous glands and no fibroplasia. Treatment consisted of CO2 laser excision of the nodular components of the hemangioma with a tightly focused beam, followed by resculpting of the natural facial contour with laser abrasion of hypertrophic soft tissues with a broad, unfocused beam. The treated area healed well, with a skin tone of a more natural color than the original hemangioma. CONCLUSION: Our findings suggest that rhinophyma may develop secondary to the vasodilation seen in large hemangiomas and that the CO2 laser offers excellent treatment for both the vascular and stromal components of the lesion. PMID- 8445106 TI - An automatic computerized bipolar coagulator for dermatologic surgery. AB - BACKGROUND: The problem with all bipolar diathermy equipment is the adherence of the tissue to the prongs of the forceps. OBJECTIVE AND METHODS: We describe a new computerized bipolar coagulator (Coa-Comp/M) with electronic feedback of the tissue impedance that automatically starts and shuts off coagulation thus preventing overheating, undue tissue damage and sticking of the forceps. The fully automation implies that no footswitch or handcontrol is necessary. The coagulator was tested during 2 years in advanced dermatologic surgery. RESULTS: A log memory recorded the number of coagulations according to effect and coagulation time. A power setting of 16W was appropriate for effective coagulation of most vessels; 99% of the coagulations were faster than 1.3 seconds necessitating automatic control for preventing sticking and charring. CONCLUSIONS: The automatic bipolar coagulator saves time and avoids sticking of the forceps. It is a useful tool in dermatologic surgery demanding repeated coagulations for hemostasis. PMID- 8445107 TI - Transplantation of melanocytes by epidermal grafting. An Indian experience. AB - Melanocyte transplantation by epidermal grafting was performed in 50 patients with localized, long-standing, stationary patches of vitiligo. Repigmentation was observed in 48 of the 50 patients within 3 to 4 months after transplantation. PMID- 8445108 TI - Glycolic acid peels for the treatment of wrinkles and photoaging. AB - BACKGROUND: Glycolic acid is an alpha hydroxyacid that is useful as a chemical peeling agent. OBJECTIVE: To discuss the techniques using glycolic acid to remove actinic keratoses, fine wrinkles, lentigines, melasma, and seborrheic keratoses. METHOD: Applied in a carefully timed manner, the depth of penetration can be titrated by the timed duration of application of acid on the skin. Chemical peels are left on the skin for 3 to 7 minutes for most patients. For ideal results, the chemical peel can be repeated 3 to 4 times. RESULT: Glycolic acid can easily be used to peel skin of all skin types with minimal risk. CONCLUSION: We have found glycolic acid can be an ideal adjunct to other cosmetic modalities such as soft tissue augmentation. PMID- 8445109 TI - Painful tumors of the skin. AB - BACKGROUND: Several cutaneous tumors are characteristically associated with considerable and sometimes incapacitating pain. OBJECTIVE: A review of the histologic features of these tumors, subjective characteristics of the pain, hypotheses proposed to explain the mechanism of pain production by the tumor, and treatments that have been effective in abolishing or relieving the patient's perception of the stimulus. METHODS: Review of case reports as well as studies that have proposed mechanisms of pain production based on histologic, electron microscopic, and pharmacologic studies. RESULTS: Several hypotheses may be equally valid in explaining the cause of pain of a single tumor type, while no apparent cause is found in other types of tumors. There is variability in the success of a treatment between patients. CONCLUSION: Our understanding of the mechanism of pain production by cutaneous tumors is limited by the small number of studies (and sample size) addressing the issue as well as by our incomplete general understanding of pain production. PMID- 8445110 TI - Pseudocyst of the auricle. AB - BACKGROUND: Pseudocyst of the auricle is a benign swelling of the ear characterized by collection of fluid within an unlined intracartilaginous cavity. The etiology and pathogenesis of this disorder remain unknown. Various forms of management have been described in several case reports and small series. OBJECTIVE: Description of a surgical procedure for successful management of pseudocyst of the auricle. METHODS: Case report of a patient who declined nonsurgical treatment options following failed management with aspiration. RESULTS: The described procedure resulted in cure of the pseudocyst with good cosmetic outcome. CONCLUSION: Pseudocyst of the auricle can be successfully managed by surgical excision of the anterior wall of the cyst. PMID- 8445111 TI - Topical tretinoin treatment in basal cell carcinoma. AB - BACKGROUND: The efficiency of topical tretinoin was examined in a patient with basal cell carcinomas (BCC) for which conventional means of removal was inappropriate. METHODS: Topical tretinoin was used to treat multiple arsenic induced superficial BCCs in a 64-year-old woman. Topical tretinoin (0.05% twice daily) was administered to four lesions for 3 weeks followed by a 3-week interruption. RESULTS: After three cycles of treatment clinical healing of all the lesions was observed. Histopathological examination of the lesional biopsies showed no evidence of a tumor. However, 9 months later all four lesions relapsed and surgical excision disclosed BCC. CONCLUSION: The data indicate that topical tretinoin treatment of multiple superficial BCCs induces clinical and pathological regression of the lesions with a high rate of relapse. This report suggests that topical tretinoin is not an effective therapy for the cure of arsenic-induced superficial BCCs. PMID- 8445112 TI - Modulation detection interference under conditions favoring within- or across channel processing. AB - A series of experiments was conducted to examine modulation detection interference (MDI) under two general conditions: one where the processing was likely to be across channel (2.0-kHz signal, 4.0-kHz masker), and the other where the possibility of within-channel processing was much more likely (2.0-kHz signal, 1.8-kHz masker). In the first experiment, MDI was measured as the modulation frequency of the signal and masker was increased from 5 to 100 Hz. The amount of MDI decreased as modulation frequency increased from 5 to 20 Hz, beyond which it remained approximately constant. This effect of common modulation frequency was somewhat smaller for the 1.8-kHz masker. The second experiment examined the effects of relative modulator phase between the masker and signal for modulation frequencies of 10 or 100 Hz. In general, there was not a consistent effect of phase. However, when the signal and masker modulators were in-phase, there was a tendency, on average, for the amount of MDI to be at a maximum when the masker frequency was 1.8 kHz and at a minimum when it was 4.0 kHz. In the third experiment, increases in masker modulation depth usually resulted in nearly proportional increases in signal modulation depth at threshold; this was true for both masker carriers, although the increase was slightly greater for the 1.8-kHz masker. The final experiment examined the effects of level for conditions where the signal and masker carriers were either equal or unequal in level. When they were equal in level, the amount of MDI increased somewhat with increases in level for both masker carriers. Comparing the amount of MDI in these conditions with those where the carriers were unequal in level revealed that the amount of MDI was considerably less when the signal was more intense than the masker. This occurred almost exclusively for the 1.8 kHz masker, however, suggesting that it may reflect a within-channel effect. Taken together, the results from the four experiments suggest that the processing underlying MDI was generally the same in the presence of both the 1.8- and 4.0 kHz masker carriers, although within-channel processing via spread of excitation probably influenced some of the results with the 1.8-kHz masker. PMID- 8445113 TI - Detection of silent temporal gaps between narrow-band noise makers having second formantlike properties of voiceless stop/vowel combinations. AB - Temporal gap detection thresholds were measured in narrow-band noise-burst markers having acoustic characteristics representative of isolated steady-state second-formant (F2) properties for/p,t,k/paired separately with/i,ae,u,o/. The results revealed that gap detection threshold increased systematically as the difference was increased between the simulated stop and vowel F2 frequencies. A strong positive correlation (r = 0.87) between gap detection threshold and linear marker center frequency difference was highly significant (p < 0.001). Differences in other stimulus features had little influence on gap detection performance. Implications for speech perception are discussed. PMID- 8445114 TI - Discriminability of narrow-band sounds in the absence of level cues. AB - Several experiments are described in which the task of the observer was to detect an intensity increment to the center tone of a narrow-band, multitone complex. The sound-pressure levels of the stimuli were equated, then randomized, so that listeners could not detect the signal by using level cues. The primary experimental variables were the number of tones in the masker spectrum, the level of the center tone or "pedestal" relative to the other tones, the center frequency and the sound-pressure level. Both "random-phase" and "fixed-phase" conditions (referring to whether the pattern of starting phases of the nonsignal tones was chosen randomly on every presentation or was held constant throughout each trial and block of trials) were tested. Although no simple detection strategy appeared to account for all of the results, the most plausible explanation for performance in most conditions was that the listeners were able to discriminate between sounds based on subtle differences in the amplitude envelopes of the waveforms. PMID- 8445115 TI - Detecting temporal onset and offset asynchrony in multicomponent complexes. AB - The ability of listeners to detect asynchrony in either the temporal onset or offset of components in multicomponent complexes was measured. The listener discriminated a standard complex, one in which all components were synchronous, from an asynchronous complex. In the initial experiments, asynchrony was created by starting (onset experiments) or ending (offset experiments) the harmonics at times drawn from a Gaussian distribution. In later experiments, asynchrony was created by starting or terminating only certain components before or after the other components in the complex. One complex consisted of 20 harmonic components with a fundamental of 200 Hz. Another multicomponent complex used components spaced at equal intervals in logarithmic frequency (200 to 4000 Hz). The parameters investigated were rise or decay time of components, duration of a complex, and frequency position of displaced components. The obtained thresholds were different for onset and offset asynchrony. For onset asynchrony in harmonic complexes, the thresholds were a nonmonotonic function of rise time with a minimum of 0.2 ms obtained for a rise time of 1 ms. For offset asynchrony, thresholds were generally monotonic with increases in decay time and ranged from 0.45-1.3 ms. Experiments with a much shorter signal duration demonstrated that forward and backward masking played little role in the observed differences in thresholds. Onset thresholds for harmonic stimuli measured as a function of the frequency region of the asynchronous component(s) showed a minimum of 0.2 ms at about 2000 Hz. The thresholds for offset were about ten times larger. For logarithmic complexes, in some conditions, thresholds were larger by nearly two orders of magnitude. Experiments in which the listeners discriminated changes either in the onset or offset envelope of the wideband stimulus suggest that detection of temporal asynchrony depends on comparison between frequency channels rather than on differences in the temporal onset or offset of the overall energy of the sounds. PMID- 8445116 TI - Discrimination of moving events which accelerate or decelerate over the listening interval. AB - Grantham [Grantham, J. Acoust. Soc. Am. 79, 1939-1949 (1986)] has proposed that subjects are able to resolve the velocity of a moving sound source simply by determining the distance traveled and the time required to complete the movement. In the current experiment, subjects were able to discriminate between accelerated and decelerated movements which were identical on both parameters; that is, the accelerated and decelerated movements began and ended at the same locus and required the same amount of time to be completed. The minimum duration required to discriminate between these two movement patterns was 310 and 90 ms, respectively, for displacements of 9 degrees and 18 degrees. These results suggest that, under some conditions, the perception of velocity in the auditory modality may be based upon something more than a simple comparison of the total distance traveled and the time required to complete the movement. PMID- 8445117 TI - Electrode position, repetition rate, and speech perception by early- and late deafened cochlear implant patients. AB - Psychophysical and speech perception studies were conducted on eight patients using the 22-electrode cochlear implant manufactured by Cochlear Pty. Ltd. Four early-deafened patients became deafened at 1-3 years of age and were implanted at 5-14 years of age. Four late-deafened (postlingual adult) patients became deafened at 38-47 years of age and were implanted at 42-68 years of age. Psychophysical studies measured the discrimination of trajectories with time varying electrode positions and repetition rates. Speech perception studies measured performance using two speech coding strategies: a multi-electrode strategy which coded the first and second formant frequencies, the amplitudes of the two formants, and the fundamental frequency; and a single-electrode strategy which coded the amplitudes of the first and second formants, and the fundamental frequency. In general, the four late-deafened patients and one early-deafened patient were more successful than the other three early-deafened patients in the discrimination of electrode position trajectories and in speech perception using the multi-electrode strategy. Three of the four late-deafened patients were more successful than the early-deafened patients in the discrimination of repetition rate trajectories. Speech perception performance in the single-electrode strategy was closely related to performance in repetition rate discrimination. The improvement in speech perception performance from the single-electrode to multi electrode strategy was consistent with successful performance in electrode discrimination. PMID- 8445118 TI - Indices of frequency and temporal resolution as a function of level. AB - Several investigators have suggested that between-subject variations in hearing aid benefit may be related to between-subject variations in auditory resolution. Evaluation of this relationship is complicated by the need to assess resolution at several frequencies and levels in hearing-impaired listeners who may not tolerate lengthy test procedures. This paper reports data from normal-hearing listeners for abbreviated indices of frequency and temporal resolution. For a particular frequency-stimulus level combination, both indices may be derived from three pure-tone thresholds obtained with different masking stimuli. Norms are reported as a function of masker level for each index at four test frequencies. Changes in the indices as a function of masker level were consistent with expectations based on related studies by other investigators. Norms were obtained using a supra-aural earphone. Comparison of results from supra-aural and insert earphones suggested that low-frequency sound leakage substantially affected the norms for 500 Hz. Reliability of individual indices was good to excellent. PMID- 8445119 TI - Voice source model for continuous control of pitch period. AB - The voiced speech waveform may be synthesized by exciting an LPC vocal tract filter with a pulse waveform patterned after naturally occurring glottal airflow pulses. Such a pulse waveform may be generated by computing samples of a piecewise polynomial curve at equally spaced time intervals. In this type of synthesis, the pitch period is commonly restricted to an integer multiple of the sample interval. A method is presented for removing this restriction, permitting both pulse duration and pitch period to be varied over continuous time. Aliasing distortion is prevented by computing the sample values of pulses that have been low-pass filtered in continuous time prior to sampling. Applications of this technique include modeling glottal pulses by least-squares fit to inverse filter waveforms, the synthesis of calibration waveforms for evaluating measures of speech waveform jitter, the perceptual evaluation of low levels of waveform jitter, and the synthesis of the singing voice. PMID- 8445120 TI - Toward the simulation of emotion in synthetic speech: a review of the literature on human vocal emotion. AB - There has been considerable research into perceptible correlates of emotional state, but a very limited amount of the literature examines the acoustic correlates and other relevant aspects of emotion effects in human speech; in addition, the vocal emotion literature is almost totally separate from the main body of speech analysis literature. A discussion of the literature describing human vocal emotion, and its principal findings, are presented. The voice parameters affected by emotion are found to be of three main types: voice quality, utterance timing, and utterance pitch contour. These parameters are described both in general and in detail for a range of specific emotions. Current speech synthesizer technology is such that many of the parameters of human speech affected by emotion could be manipulated systematically in synthetic speech to produce a simulation of vocal emotion; application of the literature to construction of a system capable of producing synthetic speech with emotion is discussed. PMID- 8445121 TI - Some empirical observations on sound level properties of recorded piano tones. AB - Preliminary to an attempt at measuring the relative intensities of overlapping tones in acoustically recorded piano music, this study investigated whether the relative peak sound levels of recorded piano tones can be reliably inferred from the levels of their two lowest harmonics, measured in the spectrum near tone onset. Acoustic recordings of single tones were obtained from two computer controlled mechanical pianos, one upright (Yamaha MX100A Disclavier) and one concert grand (Bosendorfer 290SE), at a range of pitches and hammer velocities. Electronic recordings from a digital piano (Roland RD250S), which were free of mechanical and sound transmission factors, were included for comparison. It was found that, on all three instruments, the levels of the lowest two harmonics (in dB) near tone onset generally increased linearly with the peak root-mean-square (rms) level (in dB) as hammer velocity was varied for any given pitch. The slope of this linear function was fairly constant across midrange pitches (C2 to C6) for the first harmonic (the fundamental), but increased with pitch for the second harmonic. However, there were two sources of unpredictable variability: On the two mechanical pianos, peak rms level varied considerably across pitches, even though the strings were struck at nominally equal hammer velocities; this was probably due to the combined effects of unevenness in hammer-string interaction, soundboard response, and room acoustics. Moreover, for different pitches at equal peak rms levels, the levels of the two lowest harmonics varied substantially, even on the electronic instrument.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8445122 TI - Optical transducer for reception of ultrasonic waves. AB - A new optical transducer for the detection of acoustic pressure in the diagnostic ultrasound frequency range is described. This transducer is based on the modulation of an evanescent light field by the incident acoustic energy. Theoretical design considerations are presented for the purpose of developing the most sensitive transducer. Based on these considerations an experimental transducer was constructed. Although less sensitive than predicted this device was capable of transducing ultrasonic pulses with a 1.0-MHz center frequency at diagnostic ultrasound amplitude levels. The techniques developed here are applicable for two-dimensional transduction and may prove a viable alternative to piezoelectric array transducers. PMID- 8445123 TI - Measuring the strength of auditory fusion for synchronously and nonsynchronously fluctuating narrow-band noise pairs. AB - This experiment examines the "strength" of auditory fusion for narrow-band noise pairs. Each pair of noise bands consisted of a target band and a flanker band presented simultaneously. The temporal envelopes of the noise bands within a pair fluctuated either in synchrony (synchronous condition) or not in synchrony (nonsynchronous condition). Each noise-band pair was alternated rapidly with a noise band (captor band) presented alone. The duration of the silent period between a noise-band pair and a captor band [i.e., onset-to-onset interval (OTO)] was decreased by listeners until auditory fusion of the pair was disrupted by capturing the target band into a sequential-stream with the captor band. Results showed that listeners required significantly shorter OTOs to capture the target bands from the synchronous pairs than from the nonsynchronous pairs, suggesting that strength of auditory fusion was greater for the noise bands that fluctuated in synchrony than for those that did not. The results of this experiment are discussed relative to hypotheses based on auditory stream segregation to explain auditory phenomena such as comodulation detection difference, modulation detection interference, and comodulation masking release. PMID- 8445124 TI - A note on onset effects in binaural hearing. AB - Various definitions of interaural "onset" delays in binaural stimuli have led to discrepant conclusions about the relative strength of onset versus ongoing cues. A distinction is offered here between gating (envelope-onset) delays, and early fine-structure (carrier) delays. This distinction, in conjunction with independent experimental results on the relative effectiveness of interaural envelope and carrier delays, leads to a reconciling interpretation. PMID- 8445125 TI - Objective performance analysis as a tool for the musical detective. PMID- 8445126 TI - Miniature microphone probe tube measurements in the external auditory canal. AB - The use of a miniature microphone probe tube for sound-pressure level measurements in the outer earcanal was studied in four experiments. The main reason was to evaluate this method for clinical applications and for measurements of hearing protector attenuation. All measurements were registered in 1/3-oct bands. The dynamic range, frequency response of the microphone system, the insertion loss of the probe tube walls, and the influence of the probe tube in the ear canal on the sound-pressure level were examined. The first experiment attempted to determine an optimal placement of the probe tube in the earcanal. Sound-pressure levels resulting from a known free-field sound stimulus were measured at 12 different positions in the earcanal of human subjects. The results indicated that the position which is least sensitive for small movements of the probe tube on the measure was within 1 to 3 mm of the tympanic membrane. In a second experiment the changes in sound transfer function to the tympanic membrane caused by the microphone itself, when positioned just outside the ear canal entrance, were studied for 72 angles of sound incidences in ten subjects. A few minor but significant changes were observed with the microphone in this position. In a third experiment, sound transfer functions were measured from free sound field to the tympanic membrane in 19 subjects. The measurements were performed in 1/3-oct frequency bands (0.2 to 20 kHz) with sound incidences from 24 azimuthal positions and for each of these, three different elevations. The inter- and intrasubject-variability are analyzed and discussed. Finally, the reliability of probe tube microphone measurements was evaluated by repeated measurements of the sound transfer function, five times in ten subjects with the sound incidence from one position. The results indicated very small variations between repeated measurements. PMID- 8445127 TI - Suppression of stimulus frequency otoacoustic emissions. AB - Observations of the suppression of stimulus frequency evoked otoacoustic emissions (SFOAEs) by a second tone were made in human subjects. Measurements were made with the suppressor tone at frequencies and levels at, above, and below the stimulus tone generating the SFOAE. Data were collected with the stimulus tone at a range of levels (20-60 dB SPL), over a range of frequencies and in six different ears, in three subjects. The results were fitted to a phenomenological model, which allowed the data to be expressed as two parameters against the frequency of the suppressor tone. Characteristics of the suppression were examined, in particular the asymmetry between suppression by tones of higher and lower frequency than the tone evoking the SFOAE. At relatively low levels of suppressor tone, suppressors with frequencies higher than the stimulus tone were more effective suppressors than lower frequencies. At higher levels of suppressor tone, the situation was reversed, with lower frequencies being more effective than higher frequencies. These results were discussed in terms of nonlinear interaction between waves in the cochlea. This interpretation was used to estimate the shape of the traveling wave envelope produced by the stimulus tone, from the results of the suppression experiments. It was shown that the estimates of the shapes of the traveling wave envelope were nonlinear, the peak of the envelope becoming sharper at lower levels of stimulus. A simple quantitative model of SFOAE suppression was formulated using concepts of energy flow within the cochlea. This model produced SFOAE suppression results with all the major characteristics of SFOAE suppression from a real, human ear. PMID- 8445128 TI - Derived band auditory brain-stem response estimates of traveling wave velocity in humans. I: Normal-hearing subjects. AB - Estimates of cochlear traveling wave velocity (TWV) were computed from derived band auditory brain-stem response (ABR) latencies in 24 normal-hearing subjects. Wave V latencies were determined for each of six derived frequency bands (unmasked-8 kHz, 8-4 kHz, 4-2 kHz, 2-1 kHz, 1 kHz-500 Hz, and 500-250 Hz). Representative frequencies were assigned to the derived bands by estimating their energy midpoints, and cochlear positions corresponding to these frequencies were determined using Greenwood's [J. Acoust. Soc. Am. 33, 1344-1356 (1961)] place frequency function for humans. Two procedures were used to estimate TWV. In one procedure, an exponential function of the form l = A + BeCd was fitted to each subject's latency-by-distance data using a least-squares algorithm, and a TWV function was generated by taking the inverse derivative of the latency function with respect to time. In the second procedure, average TWVs between adjacent derived bands were computed directly from subjects' ipsilateral wave V latencies. Values obtained with the two procedures were similar for middle and apical cochlear loci; however, TWV functions produced lower estimates of TWV at the most basal of five cochlear sites. TWVs based on ipsilateral wave V latencies ranged from 5.6 to 78.0 m/s (geometric mean 11.2 m/s) in the cochlear base (7.53 mm from the stapes) and from 1.2 to 3.4 m/s (geometric mean 1.96 m/s) in the cochlear apex (24.1 mm from the stapes). Intersubject variability was large at the most basal point of TWV estimation but was progressively smaller at more apical sites. Mean TWV estimates were lower than those reported by several previous investigators. The range of values obtained in various studies may stem from differences in the procedures used to estimate TWV. PMID- 8445129 TI - Effect of low-frequency "conditioning" on hearing loss from high-frequency exposure. AB - Recent research has revealed that repeated exposures to a low-frequency noise results in a progressive reduction in threshold shifts (TS). This reduction in TS is not restricted to the exposure frequency, but can be observed at frequencies up to 3 or 4 octaves higher. Such "conditioning" exposures have also been observed to protect the auditory system against hearing loss from exposures to the same noise at higher levels. The aim of this study was to determine if "conditioning" using low-frequency exposures protects the auditory system against hearing loss from a high-frequency exposure. Monaural chinchillas were exposed to a 0.5-kHz octave band noise (OBN) at 95 dB SPL for 6 h a day. The animals were allowed to recover for 5 days, following which they were exposed to a 4-kHz OBN at 100 dB SPL for 48 h. Hearing thresholds determined using evoked potential recordings, indicated significantly greater permanent threshold shifts in this group of animals when compared to a control group exposed only to the 4-kHz OBN. These results were confirmed by histological examination which revealed greater hair cell loss in the experimental group. PMID- 8445130 TI - Discrimination of spectral shape as a function of stimulus duration. AB - Thresholds for discriminating the changes in the spectral shape of simultaneously presented components (profile analysis) are measured as a function of stimulus duration for various complex stimuli. For all stimuli, the threshold decreases with increasing duration until a transition time is reached, and thereafter the threshold remains constant. The amount of change in threshold and the value of transition time appear to be greater for complexes having narrower frequency spacing of the components. The results can be accounted for, at least qualitatively, by assuming that the bandwidth of the auditory filters decreases after the onset of the stimulus. PMID- 8445131 TI - Rate of loudness growth for pure tones in normal and impaired hearing. AB - The present article provides an analysis of loudness growth rates in normal and cochlear-impaired hearing for diverse groups with respect to age and backgrounds. Slopes are obtained from absolute magnitude estimation and magnitude production of loudness (measured values), and from cross-modality matching and absolute magnitude estimation of apparent length (predicted values). Consistent with an earlier study [R. P. Hellman and C. H. Meiselman, J. Acoust Soc. Am. 88, 2596 2606 (1990)], slopes calculated within the 15-30 dB stimulus range above the elevated threshold increase in size with the degree of hearing loss. The corresponding range of loudness values in normal hearing yields a slope near 0.60 independent of the threshold levels. This pattern of loudness growth holds for individuals and groups. But the intersubject variability of the slope is more labile, being larger across than within groups and larger for the measured slopes than for the predicted values. Determined from the predicted slopes, the coefficient of variation, sigma/m, is approximately constant in normal and impaired hearing ranging from 20%-27%. In contrast, sigma/m, obtained from the measured slopes, increases with the degree of hearing loss to a value of almost 50% for a 75-dB loss. The overall stability and systematics of the observed effects further demonstrate that the loudness-intensity relation can be specified with reasonable precision and accuracy from cross-modality matching. PMID- 8445132 TI - Suppression and the dynamic range of hearing. AB - The results from experiments that have examined intensity discrimination in the presence of notched noise indicate that spread of excitation is not necessary for the auditory system to maintain a large dynamic range. In those experiments the notched noise and the pedestal were simultaneously present. It is possible, therefore, that the notched noise suppressed the pedestal, and increased the dynamic range by reducing the excitation level [A. R. Palmer and E. F. Evans, Hear. Res. 7, 305-323 (1982)]. In the experiment described here, spread of excitation was masked nonsimultaneously in order to avoid suppressive effects. The brief sinusoidal pedestal was presented in a 13-ms gap between two bursts of a masking complex. The masking complex consisted of two sinusoids at frequencies of 0.8fc and 1.2fc (where fc was the pedestal frequency), each having a level either the same as, or 10 dB below the pedestal level, and a notched noise with a spectrum level 40 dB below the level of the sinusoids. Detection thresholds were measured to ensure that the complex was effective in masking spread of excitation. Weber fractions were measured at two pedestal frequencies, 1 and 4 kHz, and at eight pedestal levels at each frequency, covering a range of 70 dB. The results indicate that, although the masking complex raised the Weber fraction by up to 10 dB in some conditions, performance was no worse at high levels than at medium or low levels. This suggests that the auditory system can maintain a large dynamic range in the absence of suppression and spread of excitation. PMID- 8445133 TI - Just noticeable differences for intensity and their relation to loudness. AB - The present study examines the relation between the form of the loudness function and the size of the intensity just noticeable difference (jnd). The hypothesis that equal loudnesses at any given sound frequency yield equal-intensity jnd's was examined. In addition, Hellman et al.'s [J. Acoust. Soc. Am. 82, 448-453 (1987)] experiment, which showed that jnd's are independent of the slope of the loudness function was replicated. Threshold shifts and altered loudness-balance functions for 1-kHz tones were produced by using backgrounds of narrow- or wideband noise. The two types of background noise produced intersecting points on loudness-balance functions at which intensity jnd's were obtained. Intensity jnd's were also obtained at equal-loudness levels (corresponding to 30, 40, 50, and 60 dB SL in the unmasked ear) under each of the two noise conditions and in quiet. The results indicate that tones of equal loudness produce approximately equal jnd's and that there is no apparent relation between the slope of the loudness-balance functions and the size of the intensity jnd. PMID- 8445134 TI - Individual differences in the improvement in spectral shape discrimination due to increasing number of nonsignal tones. AB - The effect of the number of nonsignal tones on the just-discriminable difference in spectral shape was evaluated for 12 naive subjects. The signal was an intensity increment to the center tone of a multitone complex. The tones were spaced at equal frequency ratios and, except for the signal increment, were equal in level. The number of nonsignal tones ranged from 2 to 20. Consistent with previous studies using equally spaced components, group mean thresholds improved monotonically with increasing number of tones. Group mean thresholds improved about 8 dB over the range of reference spectra employed. Large differences were found across subjects in overall performance, and in the magnitude of the improvement with increasing number of nonsignal tones. The greatest intersubject variability was observed for the stimuli composed of the fewest components. It was concluded that the differences reported in the literature concerning the presence and magnitude of the improvement are due both to differences in the procedures used and to the large individual differences that occur among subjects. PMID- 8445135 TI - Complex noise exposures: an energy analysis. AB - Industrial noise environments usually present a complex stimulus to the exposed individual. These environments often contain mixtures of multiply reflected impact noises and a relatively Gaussian broadband noise. Noise exposure standards do not consider the possibility of interactions between the two classes of noise that can exacerbate the amount of hearing trauma. This paper presents the results of a large series of experiments designed to document the hazard posed to hearing from complex noise exposures. Twenty-three groups of chinchillas with 5 to 11 animals per group (total N = 135) were exposed for 5 days to either octave bands of noise, impacts alone, or combinations of impact and octave bands of noise. Evoked potential measures of hearing thresholds and cochleograms were used to quantify the noise-induced trauma. The results show that, for sound exposure levels (SEL) which produce less than approximately 10 dB PTS (permanent threshold shift) or 5% total sensory cell loss, equal-energy exposures tend to produce equivalent effects on hearing. However, there is a range of at least 10 dB in the SEL parameter where hearing loss from equal-energy exposures at a particular SEL can be exacerbated by increasing the repetition rate of the impacts or by the addition of a Gaussian low-level noise. The exacerbation of trauma from the addition of a Gaussian continuous noise is dependent upon the spectrum of that noise. PMID- 8445136 TI - Understanding the value of teeth to older adults: influences on the quality of life. AB - Understanding the value of teeth to older adults is important in marketing dental services and motivating patients to care for their teeth. The authors surveyed more than 1,000 older adults in North Carolina to determine how teeth affect the quality of their lives. PMID- 8445137 TI - Removable prosthodontic impressions. PMID- 8445138 TI - Reimplanted primary teeth. PMID- 8445139 TI - Chronic TMD patients. PMID- 8445140 TI - FDA approves hepatitis B vaccine. PMID- 8445141 TI - The good news on office safety. PMID- 8445142 TI - Lack of evidence for patient-to-patient transmission of HIV in a dental practice. AB - This report reviews data pertaining to the hypothesis that transmission of HIV to five patients of a Florida dentist with AIDS resulted from the patient-to-patient transfer of infectious materials through the reuse of contaminated instruments. Findings strongly suggest that patient-to-patient transmission of HIV through contaminated handpieces, prophylaxis angles or anesthetic needles or cartridges did not occur in this practice. PMID- 8445143 TI - Bacteriological analysis of high-speed handpiece turbines. AB - The microbial contamination of handpiece turbines was examined clinically. In 20 handpieces, no bacterial growth was found on any culture from an autoclaved or non-autoclaved handpiece group. But growth occurred in the positive control inoculated with fresh whole human saliva. An adjunctive investigation with saliva substitute showed that oral fluids can contaminate handpiece turbines during simulated clinical treatment. PMID- 8445144 TI - Countering the concerns: how to reinforce dental practice safety. AB - Dentists must become more aggressive in anticipating patient concerns and initiating programs to answer current infection control concerns. Specific suggestions to meet these concerns are offered. PMID- 8445145 TI - What to do if OSHA calls. One dentist shares his experience. PMID- 8445146 TI - No laughing matter. PMID- 8445147 TI - Prevention and early detection: keys to oral cancer. PMID- 8445148 TI - Salivary diagnosis: more than a lick and a promise. AB - There is a growing appreciation for the use of oral fluid as an easily collected, non-invasive diagnostic medium in a variety of disease states and clinical situations. Dental applications include differential diagnosis of salivary gland disease, caries and periodontal disease activity and susceptibility tests, Candida monitoring and testing for HIV and hepatitis. PMID- 8445149 TI - How older adults use oral health care services: results of a National Health Interview Survey. AB - This report describes the dental visit patterns of adults aged 65 and older. The analyses compare dental visit patterns by socioeconomic factors, perceived health status and dentate status. PMID- 8445150 TI - Tuberculosis: a growing concern for dentistry? AB - Dentists are increasingly treating patients who have significant medically compromising conditions, a number of which predispose individuals to tuberculosis. Three case reports describe patients with histories of tuberculosis exposure. The authors also discuss risk assessment and offer practical guidelines for dental management of these patients. PMID- 8445151 TI - Diurnal modulation of rat hypothalamic gonadotropin-releasing hormone release by melatonin in vitro. AB - The mechanism(s) by which melatonin (MEL) can regulate gonadotropin secretion remains unresolved. Accordingly, we used acute in vitro incubations of male rat hypothalamic tissues to investigate effects of MEL on hypothalamic gonadotropin releasing hormone (GnRH) secretion. At 10:00 h (3.5 after lights on), addition of 1 nM MEL to the medium inhibited (p = 0.028) GnRH release from the median eminence (ME) by 24%, 100 nM MEL had no significant effect on GnRH release, and 10 microM MEL tended to inhibit (p = 0.056, 21%) GnRH release. At 15:00 h, none of these MEL dosages significantly altered GnRH release from the ME. When the effect of a lower range of MEL dosages was evaluated, 1 nM MEL again inhibited (24%, p = 0.032) GnRH release from the ME at 10:00 h, and a linear dose-response relationship between initially increasing dosages (0, 0.01, 0.1, 1 nM) of MEL treatment and decreasing GnRH release was evident (r = 0.88), although a further 10 fold increase in MEL dosage (10 nM) resulted in a loss of suppression by MEL. Treatment with these dosages of MEL did not significantly alter ME GnRH release at 15:00 h. In contrast to the results with the ME alone, treatment with 0.1 microM MEL increased (p = 0.018) GnRH release from the arcuate-median eminence region (ARC-ME) by 60.2% at 10:00 h, whereas treatment with either 0.001 or 10 microM MEL did not significantly affect GnRH release. Treatment with these dosages of MEL did not significantly alter ARC-ME GnRH release at 15:00 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8445152 TI - Physiological levels of growth hormone fail to suppress growth hormone releasing hormone (1-29) NH2-stimulated growth hormone secretion in man. AB - We studied 11 normal adult males. Six subjects (Study A) received a bolus of saline or of 50 mU biosynthetic human growth hormone (r-hGH) or a one hour iv infusion of r-hGH (80 mU/h) in random order. On each occasion this was followed by an iv bolus of GHRH (1-29) NH2 (100 micrograms) 90 minutes after the first event. Five subjects (Study B) received a bolus iv injection of saline or of 500 mU r-hGH followed by iv GHRH (1-29) NH2 (100 micrograms) 90 minutes later. There was no significant difference in the serum GH concentrations achieved following the 50 mU bolus or iv infusion of r-hGH (range 5.6-67.0 mU/l). Higher concentrations of GH (mean +/- SE, 238.4 +/- 21.3 mU/l) were achieved with the 500 mU bolus of r-hGH. The peak GH responses to iv GH-RH (1-29) NH2 were similar in all instances. The most important factor determining the response to exogenous GHRH (1-29) NH2 was the serum GH concentration at the time that the GHRH (1-29) NH2 was administered and the mode of r-hGH administration (iv bolus or iv infusion). These data demonstrate that within the range of physiological serum GH concentrations the mode of presentation of GH (bolus or infusion) and GH secretory status are the most important factors in determining GH responsivity to GHRH. Under these circumstances GH would appear not to participate in a rapid acting short-loop negative feedback mechanism in man as the response to exogenous GHRH was not attenuated. PMID- 8445153 TI - Molecular composition of two different batches of urofollitropin: analysis by immunofluorimetric assay, radioligand receptor assay and in vitro bioassay. AB - The molecular heterogeneity of two different batches of commercially available urofolitropin was analyzed after fractionation by isoelectric focusing (IEF). FSH was measured before and after IEF by a highly specific time-resolved immunofluorimetric assay (IFMA), by a radioligand receptor assay (RRA) employing a preparation of calf testis FSH receptors, and by the in vitro bioassay based on FSH-dependent aromatase stimulation in immature rat Sertoli cells. An overall good correspondence between the results obtained with the three different methods was observed. However, the RRA and the in vitro bioassay appeared to be more suitable than the IFMA in resolving individual FSH isoforms. The mean isoelectric points of the two FSH preparations analyzed were slightly different, due to different molecular composition. These differences, however, seem too minute to be considered as cause of the different pharmacokinetics of FSH described in the literature or to explain the inconsistent therapeutical results seen in patients treated with FSH of urinary origin. PMID- 8445154 TI - Restoration of lactation in bromocriptine-treated rats by prolactin replacement: comparison of constant versus pulsatile infusion and intrahepatic versus intrajugular routes of delivery. AB - The effectiveness of pulsed vs constant infusion of ovine(o) prolactin (PRL), given by different schedules, at restoring lactation in PRL-suppressed rats was compared, and the possibility that the liver participates in the restorative effects of the infused hormone was investigated. Lactating dams were given subcutaneous injections of bromocriptine (BC) between days 7 and 12 postpartum to suppress endogenous PRL secretion. Osmotic minipumps were used to infuse the oPRL into either the jugular vein or the hepatic portal vein. The latter route would expose the liver to higher concentrations of PRL than would intrajugular infusion. Constant infusion of oPRL in different doses was, overall, more effective at restoring lactation (i.e. litter weight gain) than was giving pulses, regardless of the site of delivery. Infusion of the PRL at 100 micrograms/rat/day in pulses of 1h duration was ineffective at frequencies of either 4 or 8/day, whereas pulses of 2h duration were effective at both of these frequencies. Infusing that dose of oPRL was equally effective whether it was given in 4 or 8 pulses/day of 2 h duration. Intrahepatic infusion of oPRL was not more effective than intrajugular delivery regardless of the schedule of administration. These results indicate that pulse duration is a more important determinant of the effectiveness of the galactopoietic action of PRL in the lactating rat than is pulse frequency. No evidence was obtained that the liver participates in the galactopoietic effects of PRL. PMID- 8445155 TI - Interference of thyroperoxidase on immuno-cytochemical determination of steroid receptors in thyroid tissue. AB - The presence of sexual steroid receptor proteins in thyroid tissue has been previously demonstrated by biochemical means. The aim of this study was to determine the estrogen (ER) and progesterone (PR) receptors in malignant (12 papillary and 1 follicular carcinoma) and nonmalignant (19 multinodular goiters, 1 Graves' disease, 1 Hashimoto's thyroiditis) thyroid diseases using immunocytochemical assay employing monoclonal anti-ER and anti-PR antibodies and the peroxidase-antiperoxidase technique. Positive results were obtained in 24/34 (70%) for ER (ER-ICA+) and 22/34 (64%) for PR (PR-ICA+). To evaluate the possible interference of thyroperoxidase in the immunostaining, in consecutive sections of a positive specimen, primary antibody or primary antibody plus bridging antibody or PAP complex was omitted. Using these modified procedures, staining distribution was similar to that obtained by the standard procedure: in contrast, no staining was found in the positive control, i.e. a breast cancer specimen. The inhibition of the endogenous peroxidase caused a loss of staining in both the standard and modified procedures on thyroid specimens; no staining modification was obtained in the positive control. These results suggest that the staining observed in thyroid tissue is not specific and related to the activity of thyroperoxidase on chromogen solution. The complete loss of staining after peroxidase inhibition appears to be in contrast with the results obtained by biochemical method, and different antigenicity of thyroid receptors in comparison with breast receptors may explain this discrepancy. PMID- 8445157 TI - Postoperative primary adrenal failure from bilateral hemorrhagic adrenal infarction associated with coagulation factor XI deficiency. AB - A 72-year-old man developed bilateral adrenal hemorrhage causing primary adrenal failure three days after total hip replacement, and was found to have coagulation factor XI deficiency. Factor XI deficiency usually causes mild bleeding which is not predictable on the basis of assayable factor XI levels. There have been no previous reports of bilateral adrenal hemorrhage in factor XI deficiency or other inherited coagulation factor deficiencies. We suggest that the risk of bilateral adrenal hemorrhage should be considered in any preoperative evaluation of patients with factor XI deficiency. PMID- 8445156 TI - Polymorphism of thyrotropin and alpha subunit in human pituitary adenomas. AB - To understand better why patients with TSH-secreting pituitary tumors exhibit variable degree of hyperthyroidism, we analyzed the various isoforms of TSH and alpha-subunit secreted by 4 TSH-secreting adenomas in primary culture. All patients had macrodenomas clinically associated with hyperthyroidism with normal to elevated TSH plasma levels. The in vivo molar alpha/TSH ratio ranged from 18.4 to 3.8. The hormone material secreted over 4 to 48 h in culture was separated by gel isoelectrofocusing, eluted and estimated by immunoassays. The release of free alpha-subunit was noticeably different among adenomas. Three tumors were found to release an homogeneous and acidic (pI = 5.4-4.5) species totally unrelated to the alpha-subunit dissociated from intrapituitary TSH (5 isoforms, pI = 8.8-5.8) while another was more heterogeneous (pI = 8.8, 8.4, 7.6, 6.8, 5.8, 5.4-4.5). Tumoral TSH exhibited at least six detectable isoforms (pI = 8.6, 8.3-8.0, 7.5, 7.0, 6.5, 6.0) very similar to those present in a purified intrapituitary hormone preparation. While intrapituitary TSH was composed of 70% of alkaline (pI = 8.6 7.5), 25% of neutral (pI = 7.0-6.0) and 5% (pI = 5.8-4.5) of acidic forms, these species were found to be more evenly distributed in adenomatous secretion (43%/42%/15%). The TSH-secreting tumors thus appeared to relase preferentially neutral and acidic forms of TSH than alkaline components but for one tumor, this ratio could be modified by chronic incubation with TRH. When assayed for their capacity to stimulate 3H-thymidine incorporation in FRTL-5 cells, neutral TSH appeared definitely less potent than the alkaline and acidic isohormones. Altogether, these data show that pituitary adenomas synthesize normal forms of TSH but release them in variable amount in the medium. When circulating in the blood, the ratio between active and inactive isoforms of TSH may thus be responsible for the variable stimulation of the thyroid gland observed in the patients. PMID- 8445158 TI - In vitro glucocorticosteroid and mineralocorticosteroid biosynthesis in Conn's adenoma tissues. AB - The in vitro metabolism of [1,2-3H] deoxycorticosterone (DOC), [1,2-3H] 18 hydroxy-11-deoxycorticosterone (18-OHDOC) and [1,2-3H] 11-deoxycortisol (S) was studied in adrenal adenoma homogenates from patients with primary hyperaldosteronism. Tumor tissues actively converted deoxycorticosterone and 18 hydroxy-11-deoxycorticosterone to 18-hydroxycorticosterone and aldosterone. Yields of cortisol and cortisone were also large showing that the tissues did not lack the zona fasciculata-like 11 beta-hydroxylation ability. PMID- 8445160 TI - Endemic goiter in Morocco (Skoura-Toundoute areas in the high atlas). AB - Endemic goiter in Morocco is localized in the Rif and Atlas mountains. In this study, performed in the Skoura-Toundoute areas (high Atlas), we demonstrate that iodine deficiency is the main factor involved in the development of endemic goiter. However it may not constitute the only etiological factor. The median urinary iodine excretion, measured on untimed samples, was low both in goitrous patients, m = 18 micrograms/l (n = 109) and in non goitrous subjects, m = 24 micrograms/l (n = 47). The value found in a nonendemic region (Casablanca) was much higher m = 117 micrograms/l (n = 67). Another approach to evaluate iodine intake per day was the analysis of iodine content of some samples of cereals (barley, wheat and corn), drinking water, sea and rock salt, cow and breast milk. Iodine content is low, specially in the endemic area: barley = 90 micrograms/kg (n = 1); wheat = 227 micrograms/kg (n = 1); corn = 91 micrograms/kg (n = 1); water = 0.92 to 1.30 micrograms/l (n = 3); cow milk = 6 to 33 micrograms/l (n = 10) breast milk = 10 to 55 micrograms/l (n = 14); rock salt = 420 to 660 micrograms/kg (n = 8); sea salt = 90 to 160 micrograms/kg (n = 4). Sodium chloride intake per day, estimated by the measurement of sodium and chloride urinary excretion, is normal both in the Skoura-Toundoute areas (10.7 g and 9.8 g for goitrous and nongoitrous subjects, respectively) and in Casablanca (10.9 g for control persons). Altogether the results demonstrate the importance of introducing the practice of iodinated salt in the prophylaxis of endemic goiter in this area. PMID- 8445159 TI - Ectopic secretion of growth hormone-releasing hormone in man. PMID- 8445161 TI - Social isolation: unit-based activities for impaired elders. AB - Loneliness can lead to illness and death, and is such a painful experience that a resident may not verbalize it directly. Quality nursing care requires that problems of social isolation are identified and a plan developed for adequate intervention. Impaired residents will be more successful socially when they can access a variety of interesting activities in small groups where familiar staff take initiative and establish a rapport. Institutional nurses are in a unique position to request the structural and personnel changes necessary to bring creative activities to the nursing units of impaired elders. PMID- 8445162 TI - Interdisciplinary care. Effect in acute hospital setting. AB - The Senior Care Unit was developed to meet the needs of hospitalized elderly patients. Nurses assumed leadership roles as members of an interdisciplinary care team that also included representatives from medical, social work, dietary, physical therapy, and pharmacy departments. This collaborative effort not only resulted in a more complete holistic plan of care for the patient, but also increased the nurses' and other team members' knowledge of each other's areas of expertise. This project demonstrated that it is feasible to introduce a comprehensive, interdisciplinary geriatric team coordinated by the nurses into an existing staff, resulting in quality care without increasing the length of stay or hospital costs. PMID- 8445163 TI - Management education. Needs of nurse administrators in long-term care. AB - Nurse administrators in long-term care experience relatively short tenure in the management role. Since the majority of nurse administrators in long-term care facilities have initial nursing preparation at the diploma or associate degree level, they do not receive educational preparation in leadership and management in their nursing education programs. There is a need for management education of nurse administrators in rural long-term care facilities, as perceived by chief executive officers and nurse administrators. PMID- 8445165 TI - Just in the "NIC" of time. PMID- 8445164 TI - The decade of the brain: mental health implications for elders. PMID- 8445166 TI - Self-feeding performance in nursing home residents. AB - In a study of cognitively impaired nursing home residents, excess disability was found in the specific mealtime task of drinking liquids and among those eating a pureed diet. Nursing home staff tended to rely on spoonfeeding, a process in which the resident is a passive recipient of care rather than an active participant in it, as an intervention among residents who were partially able to feed themselves. Feeding techniques other than spoonfeeding--including verbal and nonverbal prompts, and physical guiding--can support residents' participation in feeding even when independence is no longer possible. PMID- 8445167 TI - Abnormal behavioral patterns in the human fetus at term: correlation with lesion sites in the central nervous system after birth. AB - We describe three fetuses at term that demonstrated abnormal behavioral patterns in utero when observed using real-time ultrasound. The abnormal patterns turned out to have neurologic correlations after birth. In case 1, despite a normal breathing pattern, no movement in any of the four extremities was observed, thus suggesting the existence of a spinal cord lesion at the rostral end, located at C4 or C5. In case 2 a lack of breathing movement was noted repeatedly, together with the abnormal finding that alternation of periods of rapid eye movement (REM) sleep with those of non-rapid eye movement (NREM) sleep was not present. These findings implied a lesion involving the pons and/or medulla oblongata. In case 3 movement of the four extremities, breathing movement, and alternating periods of REM sleep and NREM sleep were found to be within the normal range. The concurrence of regular mouthing and the NREM sleep period was not observed, however, suggesting impairment in the brain function responsible for NREM sleep located from the pons through the thalamocortical connection to the cerebral hemisphere. PMID- 8445168 TI - Mycoplasma pneumoniae infection associated with central nervous system complications. AB - We describe two children who had central nervous system complications, encephalitis and meningoencephalitis, temporally associated with Mycoplasma pneumoniae. M pneumoniae was identified as the cause of the illnesses on the basis of at least a fourfold increase in complement fixation antibody titers. Despite extensive viral and bacterial investigation, no evidence of any other pathogen was found. Two strategies were used to determine whether M pneumoniae was directly invasive: (1) by examining cerebrospinal fluid using a M pneumoniae specific DNA probe and (2) by determining whether complement-fixating antibody to M pneumoniae was produced locally through comparison of the cerebrospinal fluid/serum ratio of M pneumoniae antibody to the cerebrospinal fluid/serum ratio of immunoglobulin M. Both assessments were negative. M pneumoniae did not appear to directly invade the central nervous system in these two patients. We conclude that the direct invasion of the cerebrospinal fluid is not necessary in the pathogenesis of M pneumoniae-induced neurologic disease. PMID- 8445169 TI - Teacher questionnaires: a classification perspective. PMID- 8445170 TI - Neurofibromatosis type 1: magnetic resonance imaging findings. AB - The purpose of this study was to determine the locations and characterize the types of brain abnormalities noted on brain magnetic resonance imaging in patients with probable and definite neurofibromatosis type 1. Patients with definite neurofibromatosis type 1 (n = 17) were studied when clinically indicated, and patients with probable neurofibromatosis type 1 (n = 9) were studied to evaluate for asymptomatic optic pathway glioma. Of the 26 patients evaluated, 14 (53%) had high-intensity signal abnormalities and 11 (42%) had significant structural abnormalities. Subsequent clinical follow-up has confirmed conversion to a definite neurofibromatosis type 1 diagnosis in three of the four cases of probable neurofibromatosis type 1 who had high-intensity signal abnormalities. The most common locations of high-intensity signal lesions were in the globus pallidus of the basal ganglia and cerebellar white matter. Tortuous or thickened optic nerves and/or optic chiasm were seen in eight cases. Brain magnetic resonance imaging scans frequently reveal high-intensity signal lesions and structural abnormalities in selected patients with both probable and definite neurofibromatosis type 1. These findings may allow for a definitive diagnosis in clinically probable cases. PMID- 8445171 TI - The Boston Teacher Questionnaire. 1. Definition of syndromes. AB - To obtain information about the academic function of 9-year-old children from their school teachers, we created a short, forced-choice questionnaire that asked about the child's knowledge and use of arithmetic tables, reading, spelling, persistence at tasks, flexibility of approach, ability to function independently, distractibility, daydreaming, impulsivity and overexcitability, hyperactivity, and ability to follow simple and sequential directions. Questionnaires were collected from the teachers of 3451 white children whose mothers had enrolled in the National Collaborative Perinatal Project. Six syndromes in girls and five in boys were identified by both cluster and factor analyses of these data. Common to both sexes were five syndromes we labeled arithmetic, tasks (ie, impersistent/dependent/inflexible), reading, attention, and hyperactive. A syndrome characterized by difficulty following directions was seen in girls only. The prevalence of these syndromes ranged from a low for hyperactivity of 2.3 per 100 girls to a high for the attention syndrome of 27.6 per 100 boys. The congruent results obtained with clustering and factor analysis, and the agreement between the observed prevalence of syndromes and prior expectations suggests that the Boston Teacher Questionnaire, as this instrument is called, identifies learning problems in 9-year-old children. PMID- 8445172 TI - The Boston Teacher Questionnaire. 2. Assessments of validity. AB - We assessed the validity of the Boston Teacher Questionnaire in a sample of 3451 9-year-old children. Those identified by the questionnaire as having a learning difficulty syndrome were compared to those without any characteristic of that syndrome. The validity reference measures were individually administered neuropsychological assessments at age 7 years and a group-administered reading achievement test at age 9 years. Girls and boys with the reading syndrome had much lower reading scores at age 9 years than did their peers. Boys, but not girls, with the arithmetic syndrome were much more likely than their peers to have arithmetic scores more than one grade below the expected level at age 7 years. Girls and boys with the tasks syndrome, characterized by impersistence, dependence, and inflexibility, were more likely than those without any features of the syndrome to be classified as having little or no goal orientation by a neuropsychologist who assessed the children in an office setting. Similarly, the neuropsychologist was much more likely than expected to have classified children with the attention syndrome as having a short attention span, and to have classified boys, but not girls, with the hyperactivity syndrome as having an unusual/extreme level and nature of overactivity. Children with any syndrome were more likely than others to have low scores on components of the Wechsler Intelligence Scale for Children, items of the Bender-Gestalt Test that assessed integration and distortion, and measures of reading comprehension. We conclude that the Boston Teacher Questionnaire validly identifies children with learning problems. PMID- 8445173 TI - The Boston Teacher Questionnaire. 3. A reassessment. AB - The prevalence of different types of dysfunction in school was assessed with the Boston Teacher Questionnaire, completed for 1923 children born 8 years earlier in a university-affiliated maternity hospital. Cluster analyses of 15 items on the questionnaire resulted in six two-item clusters and one three-item cluster that were identical for girls and boys. We identified children as having a syndrome if they possessed all features of the cluster-defined syndrome. The most prevalent syndrome, consisting of both daydreaming and distractibility items, occurred in 18.5% of boys and 11.5% of girls. Boys were also more likely than girls to be identified as having the reading syndrome (11.6% and 7.7%, respectively), the hyperactivity/impulsivity syndrome (6.1% and 1.5%), and the syndrome characterized by frustration intolerance and peer problems (9.5% and 4.0%). The prevalences of the remaining three syndromes were similar in both sexes (arithmetic, 11.3% and 10.3%; difficulty following instructions, 5.1% and 4.7%; and the tasks syndrome [characterized by impersistence/dependence/inflexibility], 5.5% and 5.4%). More than 40% of boys and girls with one syndrome also had another. The lower prevalences in this sample than in an earlier-born sample assessed with the same instrument were confined to boys. Reasons for this temporal decrease in one sex only remain obscure. Girls with the reading syndrome were 10 times more likely, and boys with the reading syndrome were five times more likely, than their peers to receive special services and to have repeated a grade. PMID- 8445174 TI - Pharmacologic management of neonatal cerebral ischemia and hemorrhage: old and new directions. AB - New developments in pharmacologic management of cerebral ischemia and hemorrhage are reviewed. A number of agents with diverse modes of action have now been shown to be neuroprotective in adult and neonatal animal models when administered either before or after a hypoxic-ischemic insult. As experience improves with these agents in hypoxic-ischemic injury and periventricular-intraventricular hemorrhage in human neonates, there is reason to be optimistic that effective neuroprotective strategies will soon be clinically available. PMID- 8445175 TI - Do pediatricians independently manage common neurologic problems? AB - Quality educational programs should ensure that pediatricians possess current knowledge, skills, values, and attitudes in child neurology. The aim of this study was to examine the relationship between pediatricians' self-confidence in neurology and their frequency of referral of children to neurologists. We distributed a questionnaire to pediatricians and pediatric trainees for self assessment of their (1) knowledge and skill in performing a neurologic examination, (2) ability to interpret neurologic findings, (3) knowledge of factual information about diseases of the nervous system, (4) ability to determine the need for investigations, and (5) ability to develop a positive attitude toward neurologic diseases. While pediatricians had significantly (P < .01) higher self-assessment scores than pediatric trainees, 54.2% of pediatricians referred 90% or more of their patients with neurologic complaints to neurologists; 74.9% of pediatricians referred more than 50% of such children to neurologists. Interestingly, pediatricians who referred over 90% of their patients to neurologists showed a significantly lower self-assessment score (P = .006) than did other pediatricians in knowledge and skill in performing a neurologic examination. As neurologists, we should develop educational programs that encourage pediatric trainees to learn to provide comprehensive care to children with common neurologic complaints. PMID- 8445176 TI - Some placental considerations related to neurodevelopmental and other disorders. AB - Many newborns who appear normal at birth later manifest substantial neurologic and other disease. Pathologists are able to explain some of that sad enigma. Placental pathology frequently reveals the pathogenesis of cerebral palsy, mental retardation, and other neurodevelopmental disorders. This requires recognition of gross placental abnormalities and insightful light microscopic examination. Chorioamnionitis is now proven to be the major cause of premature onset of labor and prematurity. There is important need for investigation of pathogenetic processes associated with ascending intrauterine infection. Major complications therein include bacterially mediated fetal hypoperfusion resulting from placental and umbilical vasocontraction. Placentas of 10% of newborns have villitis of unknown etiology. The importance of villitis is incompletely known. The fetus may discharge meconium on more than one occasion, particularly so when the fetus is postmature. Clinicians may not recognize that fetal discharge has occurred if the event occurred 4 days or more prior to delivery. Intra-amniotic meconium associated with oligohydramnios probably causes placental and umbilical vasocontraction. Meconium probably thus contributes to the pathogenesis of pulmonary vasoconstriction, persistent fetal circulation, necrotizing enterocolitis, and damage of the fetal brain, liver, and kidneys. Fetal hypoxia and asphyxia may be acutely or chronically acquired. Major placental lesions associated with neonatal asphyxia include chronic ischemic change, nucleated red blood cells, intravillous hemorrhages, intimal vascular fibrin cushions, meconium staining, and intervillous fibrin. PMID- 8445177 TI - Meeting report: Second International Rett Syndrome Workshop and Symposium. AB - Dawna Armstrong led off the summary session by reviewing the morphologic findings. Brain weights in Rett syndrome autopsy samples are 60% to 80% of expected values. Cerebral cortex has increased packing density, with decreased size of neurons and an apparently normal number of neurons, suggesting immature cortical development. Findings in the substantia nigra from Cheryl Kitt are similar. Dr Armstrong quantitated the dendritic tree in six cortical areas and found reduction in dendritic trees in all areas, with the most prominent being in the temporal lobe and the least prominent in the visual cortex. The reductions in dendritic branching do not differ with age, being the same from 4 to 35 years of age. Basal dendrites were more affected than apical dendrites, and neurons in layer 5 were more affected than those in layer 3. Dr Armstrong postulated that the increase in synaptic density from 28 weeks' gestation to birth occurred on schedule, but the secondary increase that occurs after 2 months, with a peak at 19 months, was disordered. Verne Caviness noted that these are the most informative data regarding Rett syndrome presented to date and can be summarized in three areas: (1) There is a morphologic disorder with a decrease in dendritic length, decrease in branching, and probably a decrease in the total number of synapses. He stressed that a morphologist requires a change of about 50% in the population to recognize a difference. (2) There is a dropout of certain histochemical variables, with a 93% reduction in the cholinergic system, and substantia nigra debris indicating cell death. (3) The phenomenon is generalized, with a 30% reduction volumetrically.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8445178 TI - Inability to validate a predictive score for infective endocarditis in intravenous drug users. AB - We sought to identify presenting features that should increase the accuracy of diagnosis of endocarditis in symptomatic intravenous drug use (IVDU) patients. We used two data sets of IVDU patients to develop and validate a score for endocarditis. A retrospective analysis of admitted IVDU patients was conducted with subsequent validation of endocarditis score on consecutive admitted IVDU patients at the same urban teaching hospital emergency department. Statistical comparison was made of presenting clinical features in patients with and without positive blood cultures or vegetation on their echocardiogram. Multivariable analysis of significant features was carried out. A clinical score was developed using a likelihood ratio to determine weighting. Validation of the score was tested by application to a second set of admitted symptomatic IVDU patients. The performance of the score was assessed by comparison of receiver operating characteristic curves for the two data sets. Factors associated with endocarditis on multivariable analysis were past history of endocarditis (negative correlation), total white blood cell (WBC) count, percentage neutrophils and bands on differential WBC count, infiltrate on chest x-ray, and arterial oxygenation (negative correlation). Prospective validation showed poor predictive performance of the endocarditis score. Presenting clinical, radiographic, and laboratory features do not appear helpful in estimating the clinical likelihood of endocarditis in symptomatic IVDU patients. PMID- 8445179 TI - Reemergence of self-induced abortions. AB - Two cases of adolescent females attempting self-induced abortions are presented. Many ramifications and complications of illegal abortions are discussed as they affect the patient and society. In addition, we discuss the future of medical education as well as the economic aspects of health care in relationship to illegal abortions. PMID- 8445180 TI - Trauma and English literature. PMID- 8445181 TI - Humeral head osteonecrosis caused by electrical injury: a case report. AB - Various musculoskeletal abnormalities caused by electrical injury are described. Such abnormalities usually include fractures or dislocation of adjacent bones and joints. Osteonecrosis is a noteworthy, but less common, consequence of electric shock. The case is discussed of a 52-year-old woman who had received an electric shock (220-V alternating household current) to the right hand and developed osteonecrosis in the ipsilateral humeral head, most likely caused by bone "melting." An osteonecrotic lesion may therefore develop in a joint at a distance from the point of electrical contact, and this must always be kept in mind in diagnosis and treatment. PMID- 8445182 TI - Adult respiratory distress syndrome associated with adult epiglottitis. AB - Adult respiratory distress syndrome (ARDS) is an increased permeability pulmonary edema syndrome known to be associated with a variety of direct and indirect pulmonary insults. ARDS occurred in a 37-year-old woman during an episode of epiglottitis. The patient was treated with endotracheal intubation and mechanical ventilation and recovered, to be discharged from the hospital 1 week after presentation. There are only two cases of ARDS reported in this setting, and in each case, pulmonary edema followed cardiac arrest and the patients had a fatal outcome. PMID- 8445183 TI - Self-mutilation: three cases and a review of the literature. AB - The self-mutilating patient is an unusual psychiatric presentation in the emergency department (ED). Nonetheless, serious underlying psychiatric pathology and drug abuse are important background risk factors. A careful stepwise approach in the ED is essential, although the prognosis, follow-up, and eventual rehabilitation are poor. PMID- 8445184 TI - Heroin body packers. AB - Fourteen body packers carrying 2-112 heroin packages are reported. Nine people swallowed the packets, and five inserted them rectally. The ingested packages were large and radio-opaque; they consisted of hard lumps of concentrated heroin usually covered with glove latex, white adhesive tape, and a toy balloon. There were two complications in the 14 patients. One patient developed a bowel obstruction; at laparotomy 8 packages were found in the stomach and 27 at the ileo-cecal valve. Another patient, with heroin wrapped only with black electrician's tape and no latex inner or outer wrappings, developed heroin intoxication, noncardiogenic pulmonary edema, and a bowel obstruction. Eighteen packages were surgically removed from his stomach and 26 from his bowel. We recommend bisacodyl suppositories, activated charcoal mixed with a 3% sodium sulfate cathartic, and phosphosoda enemas for package removal; close observation for heroin toxicity or bowel obstruction; and surgical intervention for continuing toxicity, retention of packages in the stomach, or bowel obstruction. PMID- 8445185 TI - Surgical cricothyrotomy performed by air ambulance flight nurses: a 5-year experience. AB - Limited information exists in the current medical literature regarding the performance of surgical cricothyrotomy by flight nurse personnel. We undertook a retrospective review of all flight records from our regional air ambulance service. The flight team transported 2,188 patients during this time; 69 patients required surgical cricothyrotomy for airway access. In all cases, the procedure was performed by a flight nurse working under a predefined airway protocol. Indications for the procedure were predominantly for maxillofacial trauma. A secure airway was established in 98.5% of the cases (68/69). Acute complications involved hemorrhage (3) and placement (3) with a complication rate of 8.7%. We conclude that surgical cricothyrotomy can be performed by well-trained flight nurses with a high success rate and an acceptable complication rate. PMID- 8445186 TI - Second-degree atrioventricular block: Mobitz type II. AB - Acute atrioventricular (AV) block occurs frequently in patients with myocardial infarction. Atrioventricular block is also a common manifestation of sclerodegenerative conduction system disease. Occasionally, heart block results from drug toxicity, hyperkalemia, cardiac valvular calcification, myocarditis, or infiltrative cardiomyopathy. Second-degree AV block is a form of "incomplete" heart block, in which some, but not all, atrial beats are blocked before reaching the ventricles. Mobitz type II second-degree block is an old term, which refers to periodic atrioventricular block with constant PR intervals in the conducted beats. The distinction between type II and type I block is descriptive; of greater importance to the clinician is the anatomic site of the block and the prognosis. In Mobitz type II block the site is almost always below the AV node; in Mobitz type I block the site is usually within the AV node. Type II AV block is more likely to progress to complete heart block and Stokes-Adams arrest. In most cases of second-degree heart block, including cases of 2:1 conduction, it is possible to determine the site of the AV block (intranodal or infranodal) using information about the age of the patient, the clinical setting, and the width of the QRS complex on the surface electrocardiogram. Second-degree atrioventricular block must be distinguished from other "causes of pauses." Nonconducted premature atrial contractions and atrial tachycardia with block are common conditions, which may mimic second-degree AV block. PMID- 8445187 TI - Distal cervical spine evaluation using swimmer's flexion-extension radiographs. AB - Radiographic evaluation of the cervical spine begins with anteroposterior, lateral, and odontoid views. Unless the junction of C7-T1 can be adequately visualized on the cross-table lateral view, a swimmer's view is often performed. After fractures and subluxations have been excluded with these nonstressed views, spinal stability may be evaluated with stressed view radiographs such as a flexion-extension series. However, there is currently no protocol for evaluating the distal spinal stability in patients in whom traditional flexion-extension radiographs fail to visualize the important distal C7-T1 juncture. The present case study describes a trauma patient suffering from neck pain in whom cervical spine instability was ruled out using a swimmer's flexion-extension technique. Further study of this technique as a supplement to the conventional flexion and extension views in the stressed assessment of the entire cervical spine is recommended. PMID- 8445188 TI - New, innovative packaging system for surgical sutures and needles. AB - A new, innovative packaging system for surgical needles and sutures has been developed that meets the special needs of emergency physicians, surgeons, and operating personnel. This packaging system consists of an overwrap, or breather pouch, as well as an innerwrap containing the needle swaged to a surgical suture. The flaps of the overwrap are offset and serrated to facilitate the opening and sterile transfer of the inner packet to the sterile field. The inner packet contains either a plastic labyrinth or craft board that maintains the suture as straight as possible until knot construction. The needle swaged to a suture is parked in foam to protect its sharp cutting edges and point. PMID- 8445189 TI - Thrombolytic therapy in review. AB - The use of thrombolytic agents for both coronary and noncoronary indications is a rapidly progressing field. There has been substantial debate over which disease processes ultimately benefit from the use of thrombolytic agents. In addition, many recent studies have focused on comparing different thrombolytic agents and dosing regimens in an attempt to gain optimal therapeutic benefit with minimal risk. This paper discusses the current status of thrombolytic therapy for coronary artery disease, pulmonary embolus, peripheral vascular thrombosis, and cerebrovascular infarction. PMID- 8445190 TI - Occupational infectious disease exposures in EMS personnel. AB - Reports of occupationally transmitted hepatitis B virus (HBV) and human immunodeficiency virus (HIV) prompted the Portland Bureau of Fire Rescue and Emergency Services (PFB) to institute a comprehensive program for handling and tracking on-the-job infectious disease exposures. Data were collected for a 2 year period beginning January 1, 1988, and ending December 31, 1989, utilizing verbal and written exposure reports, prehospital care reports, and PFB statistical information. Two hundred and fifty-six (256) exposures were categorized. The overall incidence of reported exposure was 4.4/1,000 emergency medical service (EMS) calls. Of these exposures, 14 (5.5%) were needle sticks, 15 (5.9%) were eye splashes, 8 (3.1%) were mucous membrane exposures, 38 (14.8%) were exposure to nonintact skin, 120 (46.9%) were exposures to intact skin, and 61 (23.8%) involved respiratory exposure only. The incidence of exposure of nonintact skin or mucous membranes to blood or body fluids and needle sticks was 1.3/1,000 EMS calls. Forty-eight individuals (64% of those incurring needle sticks, or exposure of non-intact skin or mucous membranes to blood or body fluids) were treated and followed for signs of infection. Of this group, 11 individuals (26%) previously vaccinated against hepatitis B demonstrated inadequate HBsAb titers at the time of exposure. Requests for HIV and HBV information on source patients were made for needle sticks or exposure of nonintact skin or mucous membranes to blood or high-risk body fluids. Information on the source patient's HIV status was obtained for 57% of these requests.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8445191 TI - The incredible rightness of being. PMID- 8445192 TI - Reperfusion revisited. AB - The field of thrombolytic treatment for a variety of clinical conditions has progressed extremely rapidly over the past decade. Unfortunately, answers to questions of the greatest interest to practicing physicians remain ambiguous. They include the following: For which problems should thrombolytic treatment be the treatment of choice? Which patients should receive thrombolytic treatment, and which should not? Which of the available thrombolytic agents is "best" for which problem in which patient? In this situation of clinical ambiguity, our experience with thrombolysis in AMI is instructive. The problems for which thrombolytic treatment are indicated have in common the attribute that they are "time-sensitive"; that is, optimal benefit is achieved with earlier initiation of treatment. We have learned that to minimize delay, emergency physicians must proactively agree with our colleagues in cardiology, family practice, internal medicine, pulmonary medicine, etc., on issues of patient selection, drug selection, and ancillary therapy. It is too late to argue such issues once the patient with a thrombotic or embolic disorder has arrived in the emergency department. By cooperating in advance, we can ensure our patients the maximum benefit from timely administration of this potent therapy while protecting them from avoidable complications and expense from its medically inappropriate use. PMID- 8445193 TI - Emergency medicine, abortion and the healing tradition. PMID- 8445194 TI - Abortion: diversity or divisiveness. PMID- 8445195 TI - Orphenadrine poisoning and review of physostigmine. PMID- 8445196 TI - Ashman's phenomenon--a source of nonsustained wide complex tachycardia. PMID- 8445197 TI - Objectives to direct the training of emergency medicine residents in in-patient pediatrics. AB - This article outlines the objectives for a resident rotation in an in-patient pediatric service. The objectives can be successfully implemented in a 2-month sequential exposure to an in-patient ward service followed by an intensive care unit rotation in the first year of postgraduate training. These objectives are a part of a continuing series in the goals and objectives to direct emergency medicine resident training on off-service rotations. PMID- 8445198 TI - Secondary injury mechanisms in acute spinal cord injury. AB - Experimental studies in animal spinal cord injury models suggest that preservation of a relatively small number of spinal axons can support neurological recovery. The second National Acute Spinal Cord Injury Study (NASCIS 2) was the first clinical trial to demonstrate that a treatment given after injury can enhance neurological recovery. In this trial, patients treated with high-dose methylprednisolone within 8 hours of spinal cord injury recovered more sensory and motor function than did those treated with placebo. In addition to demonstrating the first effective pharmacological intervention in central nervous system injury, NASCIS 2 identified several critical issues that must be investigated in future preclinical and clinical research. These include drug dose, initiation time, and duration of treatment, as well as combination therapy and injury severity. Addressing these issues systematically will require more reproducible animal models and more accurate outcome measures. PMID- 8445199 TI - Opportunities for neuroprotective drugs in clinical management of head injury. AB - Over the past 15 years, neuropathological studies, patient monitoring, and data emerging from the laboratory have significantly advanced the understanding of both primary and secondary brain damage. The challenge now rests with the clinician treating head injury, who must translate these recent developments into real benefits for the patient. Neurological deterioration after head injury may be due to the effects of secondary mechanisms in up to one-third of cases. These secondary events may follow early insults such as transient global ischemia, hematomas, or diffuse axonal injury. They may be mediated by complex cascades of biochemical processes. Many of these secondary posttraumatic events have been targeted as potential sites for pharmacological intervention. In models of focal brain ischemia, a new generation of compounds that inhibit activity of glutamate has been shown to ameliorate the severity of the ischemic insult. Other potential neuroprotective agents that are currently being clinically investigated include free radical scavengers and calcium antagonists. Preliminary findings show indications of improved neurological outcome with early administration of a number of these drugs. Because head-injured patients tend to be admitted to the hospital within hours of injury, which allows for pretreatment or early therapy, several ongoing trials are assessing safety, tolerance, and efficacy of many new therapeutic agents combined with standard management. It is hoped that the outcome of this novel approach to head injury management will be positive and will help to reduce the high morbidity and mortality associated with head injuries. PMID- 8445200 TI - The role of oxygen radicals in traumatic injury: clinical implications. AB - Lipid peroxidation is believed to be a major cause of posttraumatic cell damage and death. In patients with head and spinal injuries, this process is believed to contribute significantly to the development of permanent neurological dysfunction. Lipid peroxidation can be inhibited by pharmacological agents such as the antioxidants methylprednisolone and tirilazad mesylate. Animal models of head and spinal cord injuries have been used to investigate the physiological bases of the effects of antioxidants. These studies have found that antioxidants are capable of inhibiting posttraumatic events such as edema, metabolic dysfunction, and ischemia, indicating that lipid peroxidation participates in all of these processes. Early treatment appears to be essential for antioxidant mediated neuroprotection. The multiple levels at which lipid peroxidation causes damage suggest that pharmacological modulation of this process may be beneficial in the treatment of a wide range of neural injuries. PMID- 8445201 TI - Delivering critical care: a challenge. AB - Because of the need for rapid diagnosis and management of patients acutely stricken by either injury or illness, critical care delivery cannot be limited to intensive care units. Instead, it must span the continuum from the scene of injury or illness to the patient's eventual arrival at the intensive care unit. University Hospital in Ghent, Belgium, has developed a comprehensive system that involves prehospital and in-hospital critical care, as well as a rapid and efficient interhospital and intrahospital transportation system. The prehospital system consists of a mobile intensive care ambulance, rapid-response systems known as flying squads, and a rendezvous system coordinating the ambulances and the rapid-response systems. The flying squad is staffed by a physician and the ambulance by a physician or a medical student in the last year of study. Both are also manned by an emergency department nurse and a professional driver who is also an emergency medical technician. The emergency department and its staff are available 24 hours a day to ensure uninterrupted delivery of critical care, including when patients are transported between various hospital departments. In addition, critical care specialists with at least 2 years' intensive care experience are available 24 hours a day. They also serve as coordinators for disaster planning for the hospital and the city of Ghent and its province. PMID- 8445202 TI - Pharmacological treatment of acute spinal cord injury: current status and future projects. AB - The multicenter, double-blind, randomized second National Acute Spinal Cord Injury Study (NASCIS 2) was conducted to assess the effectiveness of methylprednisolone in improving neurological function after acute spinal cord injury. At 6 weeks, patients treated within 8 hours of injury with methylprednisolone, given as an initial bolus of 30 mg/kg followed by infusion of 5.4 mg/kg/h over 23 hours, demonstrated significantly greater improvement in motor function and touch sensation than did those receiving either naloxone or placebo. Improvement in pinprick sensation was also greater in the methylprednisolone group. These differences were maintained at 6 months and 1 year after injury. The recovery of motor and sensory function in methylprednisolone-treated patients was found to be due primarily to reductions in the severity of the lesion in the spinal cord itself rather than to improvements in the level of injury or root function. A new trial, NASCIS 3, is evaluating a 48-hour course of methylprednisolone infusion as well as treatment with tirilazad mesylate, an inhibitor of lipid peroxidation without glucocorticoid activity. PMID- 8445203 TI - GM-1 ganglioside and motor recovery following human spinal cord injury. AB - Neurological deficit resulting from spinal cord injury varies widely in severity, ranging from transient abnormal reflexes to lifelong complete absence of motor and sensory function. Medical treatment to aid damaged neurons to recover function has been very limited; therapeutic efforts have focused primarily on initial stabilization of fractures, hemodynamic resuscitation, and then aggressive rehabilitation to enhance the full development of any remaining neuronal activity. Pharmacological treatment to improve restoration of neurological function may be possible, however, as indicated by many animal studies and a few clinical studies with a number of agents. A recent clinical trial of GM-1 ganglioside conducted in patients with spinal cord injuries showed that GM-1 ganglioside enhanced the recovery of neurological function 1 year after major spinal cord injury. In addition to GM-1 ganglioside treatment, these patients received aggressive medical and surgical treatment, as well as methylprednisolone. Neurological recovery was assessed with the Frankel scale and the American Spinal Injury Association (ASIA) motor scale. The findings show enhanced motor recovery compared with placebo in the lower extremities, but not in the upper extremities, over time. This corresponds to improved function of axons passing through the site of injury. Analysis of individual motor groups showed that neurological recovery in the GM-1 ganglioside-treated patients increased in initially paralyzed muscles, enabling them to regain useful motor function; paretic muscles were not found to be strengthened. The study provides the basis for larger studies of GM-1 ganglioside and methylprednisolone, which are currently under way. PMID- 8445204 TI - Mechanisms of brain injury. AB - Head injuries vary widely in their etiology, pathophysiology, clinical presentation, and optimal treatment strategies. Broadly speaking, there are two categories of brain injury: focal injuries and diffuse injuries. Focal brain injuries, which are usually caused by direct blows to the head, comprise contusions, brain lacerations, and hemorrhage leading to the formation of hematoma in the extradural, subarachnoid, subdural, or intracerebral compartments within the head. Diffuse brain injuries, which are usually caused by a sudden movement of the head, comprise classical brief cerebral concussion and more prolonged posttraumatic coma, also known as diffuse axonal injury. Primary traumatic effects involve neural or vascular elements of the brain, which can be affected by delayed effects such as deafferentation or secondary events such as ischemia, swelling, cerebral edema, and increased intracranial pressure. Axonal damage at the node of Ranvier results in a traumatic defect in the axonal membrane that causes the excessive accumulation of calcium ions within the intracellular compartment of the axon. Brain ischemia can result in a similar effect, further increasing the accumulation of calcium ions, which can lead to axonal degeneration. Injury-specific treatments are now being designed to alter the various pathophysiological mechanisms of brain injury. PMID- 8445205 TI - Rehabilitation following injury to the spinal cord. AB - There are several key aspects in the rehabilitation of patients with traumatic spinal cord injury, including the delivery of lifelong resources and services. Rehabilitation must commence as early as possible after the injury and encompass secondary and tertiary prevention efforts in order to minimize the personal and social consequences associated with neurotrauma. Recent advances in molecular neurobiology and new information gained from randomized clinical trials may help reduce the consequences of this type of injury. These advances need to be extended and research must be encouraged. PMID- 8445206 TI - Assessing the socioeconomic impact of improved treatment of head and spinal cord injuries. AB - Assessment of improved treatment of neurotrauma presents two basic challenges: 1) measurement of the medical effects of treatment, and 2) evaluation of these effects in socioeconomic terms. A nationwide survey was conducted in 1988 to estimate the prevalence of persons in the United States who suffered traumatic spinal cord injury and to calculate its economic consequences. Seven hundred fifty-eight persons weighted to be representative of the spinal cord injury population were interviewed. The prevalence rate was found to be 721 cases per million people. Conservative calculations for 1988 showed that the average direct costs per person were $103,000 for hospitalization and home modifications during the first 2 years postinjury and $14,000 per year thereafter for medical care. Losses in earnings and homemaker services averaged $12,726 per year. Total aggregate costs for 1 year were estimated at $5.6 billion. Lifetime costs for a representative person with complete paraplegia injured at age 33 were estimated to be $500,000. For a representative person with complete quadriplegia injured at age 27, these costs amounted to $1 million. These data can be used to estimate cost savings related to decreased disability resulting from improved treatment. PMID- 8445207 TI - When should a decision to proceed with transplantation actually be made in cases of fulminant or subfulminant hepatic failure: at admission to hospital or when a donor organ is made available? PMID- 8445208 TI - Effects of terlipressin on hemodynamics and oxygen content in conscious portal vein stenosed and cirrhotic rats receiving propranolol. AB - Terlipressin is used in patients with variceal bleeding but its effects in patients receiving beta-adrenergic antagonists are unknown. In this study, the hemodynamic effects of terlipressin were evaluated in conscious portal hypertensive rats which had previously received a single dose of propranolol. Moreover, oxygen content and acid-base status were studied. In portal vein stenosed and cirrhotic rats, the addition of terlipressin (0.05 mg/kg) to propranolol (0.4 mg/kg) produced a decrease in portal pressure of 34% and 17%, respectively, and in portal tributary blood flow of 46% and 42%, respectively. In cirrhotic rats, however, the decrease in portal pressure was not significantly different when propranolol was combined with terlipressin than when propranolol was administered alone. Cardiac index also further decreased after terlipressin administration. In both groups of rats, these values were similar to those observed after terlipressin alone. In portal vein stenosed rats but not in cirrhotic rats, arterial pH was significantly lower following the combination of propranolol plus terlipressin than following saline, propranolol or terlipressin alone. In conclusion, terlipressin further reduces both portal pressure and cardiac index in rats with portal hypertension receiving beta-blockers. In portal vein stenosed rats but not in cirrhotic rats, the addition of terlipressin to propranolol induces acidemia. This study suggests that terlipressin might further reduce portal pressure in patients with portal hypertension treated with beta blockers. PMID- 8445209 TI - Iron increases ethanol toxicity in rat liver. AB - Clinical evidence indicates that patients with iron overload are more susceptible to liver cell damage from alcohol than persons with normal iron stores. Iron may act as a co-factor to catalyze the lipid peroxidation induced by hepatotoxic compounds such as alcohol. To elucidate the role of iron in ethanol-induced hepatocellular damage, we developed a new experimental model in the rat. Following dietary carbonyl iron feeding for 8 weeks, animals were pair-fed a liquid ethanol diet for 4 weeks. In iron-fed animals the liver iron content was 6.4 vs. 0.5 micrograms Fe/mg protein in the controls. Blood alcohol concentrations were similar in all ethanol-fed animals. Serum alanine aminotransferase (ALT) levels were elevated to 269 +/- 49 U/l in the iron+alcohol group compared to 52 +/- 6 U/l in the other groups. There was a strong correlation between ALT levels and hepatic iron content in the ethanol-fed animals. Morphologically, the alcohol-fed rats displayed hepatic steatosis, whereas occasional inflammation and iron in Kupffer cells was seen in the iron+alcohol animals. Ultrastructurally, necrotic hepatocytes and cells phagocytosed by Kupffer cells were only encountered in the iron+alcohol group. Compared to controls, the liver content of hydroxyproline was significantly increased in the iron+alcohol group. No morphological evidence of fibrosis was noted. The present study demonstrates biochemical and morphological evidence of increased hepatocellular damage following the combination of iron and ethanol. PMID- 8445210 TI - Hypotension in experimental cirrhosis. Is loss of vascular responsiveness to norepinephrine the cause of hypotension in chronic bile-duct-ligated dogs? AB - It has been postulated that one of the mechanisms of hypotension associated with cirrhosis is an attenuated responsiveness to catecholamines despite the increased activity of the sympathetic nervous system and the elevated plasma concentrations of the sympathetic neurotransmitter, norepinephrine. This abnormality was studied in a dog model of portal hypertension and cirrhosis. Twelve weeks after bile duct ligation (n = 16), intrasplenic pressure rose significantly from 6.3 +/- 0.4 to 14.6 +/- 1.6 mmHg (p < 0.05), mean arterial pressure had fallen from 106 +/- 4 to 83 +/- 8 mmHg (p < 0.01), cardiac output had risen from 3.1 +/- 0.2 to 3.8 +/- 0.8 l/min (p < 0.05) and plasma norepinephrine concentrations rose from 0.22 +/- 0.12 to 1.17 +/- 0.52 nmol/l (p < 0.05). In 7 sham-operated dogs, the changes in these 4 variables over the same period were non-significant. In vivo pressor responsiveness was tested by studying the effects of intravenous and intra arterial infusions of norepinephrine and the non-selective beta-adrenoceptor agonist, isoproterenol. In vitro responsiveness was tested by measuring the effects of isoproterenol on the isometric twitch of isolated ventricular strips and the effects of norepinephrine on femoral, mesenteric and renal arterial rings. There was no significant change in the in vivo responses of chronic bile duct-ligated dogs at 12 weeks compared to the preoperative assessment, or to sham operated dogs at 12 weeks. Furthermore, there was no significant difference between the in vitro responses of ventricular strips to isoproterenol or arterial rings to norepinephrine prepared from chronic bile-duct-ligated and sham-operated dogs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8445211 TI - Emergency liver transplantation for acute liver failure. Evaluation of London and Clichy criteria. AB - Two sets of prognostic indicators were recently proposed for selection of patients with acute liver failure for emergency liver transplantation. According to the London criteria, patients with non-paracetamol-induced acute liver failure should be referred for liver transplantation when the prothrombin time is > 100 s or when any three of the following prognostic indicators are present: age < 10 or > 40 yr; non-A, non-B hepatitis, halothane hepatitis or idiosyncratic drug reaction; duration of jaundice before onset of encephalopathy > 7 days; prothrombin time > 50 s; serum bilirubin > 300 mumol/l. According to the Clichy criteria, in acute viral hepatitis, liver transplantation should be decided in patients with coma or confusion, and Factor V < 20% (age < 30 yr) or < 30% (age > 30 yr). To assess the accuracy of these criteria, 81 non-transplanted patients with non-paracetamol-induced acute liver failure were retrospectively studied. The mortality rate was 0.81. The predictive accuracies, respectively on admission and 48 h before death, were 0.80 and 0.79 for the London criteria, and 0.60 and 0.73 for the Clichy criteria. The positive and negative predictive values, 48 h before death, were 0.89 and 0.47 for the London criteria, and 0.89 and 0.36 for the Clichy criteria, respectively. In the 49 patients with acute viral liver failure, the results of the Clichy criteria were similar. In a subgroup of 24 patients who had not received either fresh frozen plasma or sedative-hypnotic drug, the positive predictive values were equal to 1 for the two sets of prognostic indicators, but the predictive accuracies only slightly increased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8445212 TI - Simultaneous steroids/interferon therapy in chronic hepatitis B. PMID- 8445213 TI - Requiem for the direct hepatotoxicity of ethanol. PMID- 8445214 TI - Hepatic artery mycotic aneurysm as a cause of hemobilia. PMID- 8445215 TI - Cerebral blood flow and the hyperdynamic circulation of rats after portacaval anastomosis. AB - Both increased and decreased values of cerebral blood flow have been reported in liver disease. Furthermore, the relation between the cerebral circulation and the generalized hemodynamic disturbance seen in chronic liver disease with portal systemic shunting has not been fully characterized. We studied this problem in a well defined model of the hyperdynamic circulation, the rat after portacaval anastomosis (PCA). Using the radioactive microsphere technique, cardiac output and regional blood flows were measured; regional vascular resistances were then calculated. While the fraction of cardiac output perfusing the splanchnic bed was significantly increased, the corresponding brain fraction was reduced. Blood flow to the cerebral hemispheres and midbrain was significantly decreased. Arterial vasodilatation was demonstrated by the fall in arterial pressure, systemic vascular resistance as well as splanchnic and renal resistances; cerebrovascular resistance, however, was unchanged. No relation between values of arterial pressure and cerebral blood flow was seen, making a failure of cerebrovascular autoregulation unlikely. The decrease in hemispheric and midbrain perfusion without changes in vascular resistance suggests that a drop in blood flow is appropriately coupled to a reduction in brain metabolism. The cerebral circulation does not participate in the hyperdynamic state that is seen in this model. PMID- 8445216 TI - Comparison of in vivo and ex vivo porcine liver function using the same liver. AB - In vivo and ex vivo liver function was compared using the same livers to exclude interanimal variation in hepatic function. Six male pigs were anesthetized, and catheters and perivascular flow probes placed for transhepatic sampling and hepatic arterial and portal venous flow measurement. After a 2-h in vivo study period, the livers were resected and studied immediately afterwards for a further 2 h ex vivo as an isolated perfused preparation (Experiment A). Hepatic function in a further 6 pig livers (Experiment B) was studied ex vivo only for comparison with the ex vivo livers from Expt. A to determine whether the prior in vivo study had affected hepatic function. Despite using the same livers with similar total hepatic blood flows, (0.91 +/- 0.16 ml.g-1 x min-1) in vivo and (0.84 +/- 0.03 ml.g-1 x min-1) ex vivo, hepatic oxygen consumption (6.5 +/- 0.9 vs 2.6 +/- 0.2 ml O2 x 100 g-1), adenosine-5-triphosphate content (5.22 +/- 0.62 vs 4.14 +/- 0.71 microM.g liver-1) and bile flow (15.1 +/- 1.2 vs 6.0 +/- 1.0 ml.h-1) were initially less ex vivo and remained so throughout the study, while perfusate potassium (initially) (3.7 +/- 0.1 vs 6.4 +/- 0.3 meq.l-1), and aspartate aminotransferase (50 +/- 9 vs 76 +/- 5UL-1) was consistently higher than in vivo values. Initial hepatic energy charge (0.620 +/- 0.034 vs 0.552 +/- 0.061) and total adenine nucleotides 12.49 +/- 0.60 vs 11.66 +/- 0.62 microM.g liver-1) were not different and remained so subsequently.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8445217 TI - AIDS-related cholangitis: diagnostic features and course in 15 patients. AB - About 60 cases of cholangitis in patients with the acquired immune deficiency syndrome (AIDS) have been described. We report our experience concerning 15 patients infected with the human immunodeficiency virus (HIV) and who had cholangitis as defined by radiological findings. Cholangitis was the revealing event of AIDS or HIV infection in 4 patients (27%). Twelve (80%) of the patients were homosexual men. The main diagnostic features were abdominal pain (73%), cholestasis without jaundice (100%), intestinal cryptosporidiosis (80%) and abnormal findings on abdominal ultrasonography (87%). Endoscopic retrograde cholangiopancreatography appears to be essential for diagnostic and therapeutic purposes, particularly for patients with papillary stenosis who represented 64% of our population. Biological and morphological pancreatic abnormalities were associated in 2 of the 8 patients who underwent retrograde opacification of the Wirsung duct. The microbiological yield was highest in patients who underwent multiple biopsies (duodenal and papillary) and bile sampling. The organisms found included Cryptosporidium (57%) of cases), CMV (28%) and Microsporidia (7%). Twelve-month survival after the diagnosis of cholangitis was only 14% and all deaths were related to AIDS progression. Endoscopic sphincterotomy relieved abdominal pain in 86% of the patients who underwent the procedure. Evaluation of medical treatment, particularly ursodeoxycholic acid, is necessary. PMID- 8445218 TI - Angiotensin-converting enzyme (ACE)-inhibition in cirrhosis. Pharmacokinetics and dynamics of the ACE-inhibitor cilazapril (Ro 31-2848). AB - The angiotensin-converting enzyme (ACE)-inhibitor, cilazapril, is converted to its active metabolite, cilazaprilat, by ester hydrolysis in the liver. The pharmacokinetics and pharmacodynamics of a single 1 mg oral dose of cilazapril were investigated in 10 healthy volunteers and in 9 cirrhotic patients with compensated cirrhosis and portal hypertension. A significantly increased mean plasma peak concentration (40.0 +/- 13.6 ng/ml vs. 25.5 +/- 7.9 ng/ml; p < 0.05) and a decreased apparent oral clearance (7.8 +/- 6.0 l/h vs. 16.4 +/- 5.4 l/h; p < 0.05) of cilazapril were found in cirrhotic patients compared to healthy volunteers. The plasma concentration of cilazaprilat declined in 2 phases. In both phases the plasma half-life was significantly longer in patients with cirrhosis (1st phase: 2.5 +/- 0.8 h vs. 1.7 +/- 0.6 h; p < 0.05; 2nd phase: 46.2 +/- 16.6 h vs. 28.8 +/- 4.7 h; p < 0.001). Consequently, cilazaprilat concentrations at 24 h were higher in patients than in volunteers (1.42 +/- 0.33 ng/ml vs. 0.87 +/- 0.14 ng/ml; p < 0.001). The predose activity of the ACE (26.3 +/- 7.3 U/l vs. 16.8 +/- 4.5 U/l; p < 0.005) and plasma renin activity (3.3 +/- 3.2 ng/ml/h vs. 1.4 +/- 1.0 ng/ml/h) were higher in patients than in volunteers. Maximum ACE-inhibition occurred at similar times in patients (2.7 h) and volunteers (2.3 h). Maximum ACE-inhibition was slightly higher in volunteers (94.6%) than in patients (90.6%). At later time points (> 24 h), however, ACE inhibition was more pronounced in patients (at 72 h: 39.6 +/- 6.9% vs. 23.5 +/- 8.2%; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8445219 TI - Hepatic excretion and metabolism of polyethylene glycols and mannitol in the cat. AB - The biliary clearances of fluid phase markers like erythritol and mannitol have been used to estimate canalicular bile flow. Larger fluid phase marker molecules like polyethylene glycol (PEG) 900 are excreted more extensively into bile, and it has been suggested that the biliary clearance of these give a more accurate measure of canalicular water flux than those of erythritol and mannitol. In this study, the biliary excretion of PEG 900 was compared with that of mannitol during choleresis induced by either sodium taurocholate or secretin. The biliary excretion of PEG 900 exceeded that of mannitol by a factor of 94. The biliary clearance of these markers was not influenced by secretin-induced choleresis. Using ion-exchange chromatography and fast atom bombardment mass spectrometry (FABMS) it was demonstrated that 26% of the PEG molecules are excreted into bile after oxidation to carboxylic acids, whereas sulphate conjugation is negligible. The majority of the PEG molecules (74%) were secreted unchanged, which supports the hypothesis of a mainly passive movement of PEG with the water flux into bile. FABMS showed an enrichment of larger PEG molecules in bile, which supports a previous finding that among differently sized PEGs the 1074-Da molecules have the highest biliary excretion. PMID- 8445220 TI - Prognostic significance of portal hemodynamics in patients with compensated cirrhosis. AB - The prognostic value of portal hemodynamics, measured by pulsed echo-Doppler, was prospectively evaluated, together with clinical, biochemical and endoscopic parameters, in a series of 50 consecutive patients with compensated cirrhosis. After a mean follow-up of 6 years, 25 patients had died, all from complications of liver disease. Among conventional variables, the step-wise Cox model showed that only the Child-Pugh score independently predicted death (chi 2 = 18.66; p < 0.001). When hemodynamic parameters were added to the Child-Pugh score in the same model, portal blood velocity was shown to add prognostic significance (improvement in chi 2 = 14.06; p = 0.0002; Wald test). The present study shows that a portal blood velocity below the lower limit of controls (10 cm/s) characterizes patients with shorter survival, and suggests that this non-invasive parameter should be associated to the Child-Pugh score in the evaluation of patients with cirrhosis. PMID- 8445221 TI - Gallbladder emptying is an important factor in fragment disappearance after shock wave lithotripsy. AB - The role of gallbladder emptying in fragment disappearance following shock wave lithotripsy of gallstones is poorly understood. We studied gallbladder motility in two groups of patients who had been treated by electrohydraulic shock wave lithotripsy and bile acid dissolution therapy. Group I (n = 20) consisted of patients with fragment disappearance within 18 months after lithotripsy, while patients in group II (n = 20) still harboured fragments in the gallbladder 18 months after lithotripsy. Fasting gallbladder volume was 19 +/- 10 ml (mean +/- S.D.) in group I, and 24 +/- 12 ml in group II (not significant). The residual volume was 8 +/- 9 ml in group I, but 18 +/- 14 ml in group II (p < 0.005). Thus, patients in group I ejected nearly twice as much of the fasting gallbladder volume as patients in group II. This difference in gallbladder emptying was still present if only the patients with single stones were compared in both groups. From the results of this retrospective study we conclude that gallbladder emptying is an important factor for complete fragment disappearance after gallstone disintegration by extracorporeally generated shock waves. Further prospective studies are needed to confirm these observations. PMID- 8445222 TI - Excretion of caffeine and its primary degradation products into bile. AB - Caffeine, widely consumed in beverages, is known to alter several biliary parameters that can affect gallstone pathogenesis. To address the question whether methylxanthines can act on the luminal side of biliary epithelial cells, we measured caffeine and its primary demethylation products in human bile. Eight patients had an external biliary drainage due to bile duct or gallbladder disease. Two of the patients suffered from histologically confirmed liver cirrhosis. The levels of caffeine, paraxanthine, theobromine, and theophylline were monitored over 10 h in plasma and bile before and after a prior oral dose of caffeine (5 mg/kg b. wt.). Methylxanthines were enriched by an organic extraction procedure and separated by reversed-phase high-performance liquid chromatography. Time-concentration curves in bile paralleled the time-course of methylxanthine levels in blood plasma. Accordingly, values in bile and blood plasma were highly correlated for each methylxanthine measured. Within 1 h after the oral test dose, peak levels of caffeine were obtained in both fluids. Biliary concentrations were either almost equal (caffeine) or lower (dimethylxanthines) than their respective values in blood plasma. The results of our study indicate that minor amounts of caffeine and its primary degradation products are excreted via the bile allowing local interference with epithelial cell metabolism of bile ducts and gallbladder. PMID- 8445223 TI - A comparison of transjugular and plugged-percutaneous liver biopsy in patients with impaired coagulation. AB - Patients with liver disease frequently have impaired blood coagulation. The optimal method for liver biopsy in this situation is not established. To investigate this issue we randomised 117 patients with impaired blood coagulation, in whom liver biopsy was required, to receive either transjugular or plugged-percutaneous biopsy. Seventeen patients were excluded prior to biopsy and a protocol biopsy was performed in 100 patients (44 transjugular, 56 plugged percutaneous). Liver tissue was obtained in 97 (42 transjugular, 55 plugged percutaneous). Plugged-percutaneous liver biopsy was quicker and easier than transjugular liver biopsy and the biopsies obtained were significantly larger (12 +/- 5 mm vs. 6 +/- 4 mm; p < 0.001). However, 2 of 56 (3.5%) patients who received plugged-percutaneous biopsy had haemorrhage which required transfusion, while none of the 44 patients who received transjugular biopsy had haemorrhage (not significant). Both methods of liver biopsy were associated with a high success rate and a low incidence of complications. Plugged-percutaneous liver biopsy provides larger biopsies but may be associated with an increased risk of haemorrhage. PMID- 8445224 TI - Reduced splanchnic vasoconstriction to angiotensin II in conscious rats with biliary cirrhosis. AB - Decreased pressor reactivity to angiotensin II has been demonstrated in portal hypertension due to cirrhosis. The present study investigated the respective roles of portal hypertension and cirrhosis and the hemodynamic mechanisms of the depressor response in different models of portal hypertension in conscious rats. Dose-pressor curves were studied in sham-operated, portal vein stenosed (portal hypertension without cirrhosis) and biliary cirrhotic rats following angiotensin II administration. Decreased pressor response was observed in cirrhotic rats but not in portal vein stenosed rats. The hemodynamic effects of angiotensin II administration (11 ng.100 g-1 body wt.min-1, i.v.) were studied in conscious sham operated and biliary cirrhotic rats (radioactive microsphere method). The percentage of change from basal values following angiotensin II administration were significantly more marked in sham-operated rats than in cirrhotic rats for mean arterial pressure (+34 vs. +6%), cardiac index (-36 vs. -22%), systemic vascular resistance (+117 vs. +40%). After angiotensin II, portal tributary and hepatic artery blood flows significantly decreased in sham-operated rats (-31 and -14%, respectively) but not in cirrhotic rats (+1 and +23%), whereas changes in renal blood flow were not significantly different between the two groups (-44 vs. -34%). In conclusion, in biliary cirrhotic rats, decreased pressor response to angiotensin II depends on the presence of liver disease rather than on portal hypertension or basal hemodynamic alterations. It also depends on the decreased vasoconstrictive effect which predominates in the splanchnic vascular bed. PMID- 8445225 TI - A randomized, controlled trial of weekly administration of lymphoblastoid interferon in patients with chronic hepatitis C. AB - To evaluate the efficacy of a treatment of weekly interferon administration in patients with chronic hepatitis C, 36 patients were randomly assigned to two groups. In one group lymphoblastoid interferon was given at a dose of 6 million units, intramuscularly, once per week for 24 weeks, and no treatment was given to the other. Serum alanine aminotransferase levels in the treated group were significantly lower during therapy than in the control group, although there was no significant difference between these two groups before therapy. The normalization of serum alanine aminotransferase levels at the end of therapy was observed in 50% of the treated group, and in 11.1% of the control group. This difference was statistically significant (p < 0.03). Response to interferon was better in patients with chronic persistent hepatitis or with chronic active hepatitis than in patients with chronic active hepatitis with cirrhosis. Relapse after the end of therapy was observed in 83.3% of the responders. These results indicate that the weekly administration of 6 million units of lymphoblastoid interferon is effective in decreasing serum alanine aminotransferase levels in patients with type C chronic persistent hepatitis or chronic active hepatitis. PMID- 8445226 TI - Effects of carbohydrate intake on the blood ethanol level and alcoholic fatty liver damage in rats. AB - Effects of carbohydrate (CHO) intake on the blood ethyl alcohol (ethanol) level were studied in rats with a surgically placed gastric cannula. A basal diet (protein, 2.07; fat, 1.98; CHO, 5.76 g/day), a high-CHO diet (CHO, 4.39 g/day) + ethanol, a medium-CHO diet (CHO, 2.69 g/day) + ethanol or a low-CHO diet (CHO, 0.98 g/day) + ethanol was infused into the stomach for 4 weeks starting from the 2nd postoperative week. The basal diet and the test diets were isocaloric, and the ethanol (2.80 g/day) in the test diets accounted for 39% of the total calories. The liquid diets (50 kcal in 50 ml) were infused over 16 h from 16.00 to 08.00 h each day. The low-CHO diet group had significantly higher blood ethanol levels than the high-CHO diet group 4, 8 and 16 h after the start of infusion. These groups could be ranked by liver triglyceride content at autopsy as follows: low-CHO > medium-CHO > high-CHO > or = basal. Consistent with the triglyceride content, histological changes of the liver could be ranked by the degree of fatty changes in the same order: low-CHO > medium-CHO > high-CHO > basal. Thus, for a given amount of ethanol consumption, lower CHO intake was associated with higher blood ethanol levels and with more severe fatty changes of the liver. PMID- 8445227 TI - Serum bile acids and esterified bilirubin in early detection and differential diagnosis of hepatic dysfunction following orthotopic liver transplantation. AB - Routine laboratory tests are of little help for early detection and differential diagnosis of hepatic dysfunction following orthotopic liver transplantation (OLT). In the present study, serum levels of esterified bilirubin, total bilirubin and bile acids were investigated in 20 patients after OLT. Twenty episodes of liver dysfunction were observed: 10 rejection episodes, 3 cases of thrombosis of the hepatic artery, 3 cases of septic shock, and 4 episodes of cyclosporin toxicity. During rejection, the median increase in esterified bilirubin was 3.2-fold (range 1.6-24.9), while total bilirubin increased 1.5-fold (range 0.7-3.4). Bile acids increased 3.6-fold (range 2.5-6.6; peak levels 25-87 microM). Both bile acids and esterified bilirubin increased 1-3 days earlier than serum transaminases and decreased only after successful anti-rejection treatment. The response of bile acids to successful treatment was usually more rapid than the response of esterified bilirubin. Hepatic artery thrombosis and septic shock were associated with a sharp increase in esterified bilirubin and very high bile acid levels (peak levels 80-185 microM). During cyclosporin toxicity, a characteristic pattern of progressively increasing bilirubin with no change in the bile acid levels was observed. Both esterified bilirubin and bile acids are very sensitive indicators of hepatic graft dysfunction. In particular, serum bile acids are useful for identifying cyclosporin toxicity and monitoring the response to anti-rejection treatment. PMID- 8445228 TI - An escalating dose regime of recombinant interferon-alpha 2A in the treatment of chronic hepatitis C. AB - Interferon-alpha (IFN-alpha) has proven useful in the treatment of chronic hepatitis C, but a relapse in response is frequently observed. The possible benefit of daily administration of recombinant IFN-alpha 2A at an escalating (from 1.5 to 9 MU) regime depending on the evolution of serum aminotransferase (ALT) levels was evaluated in 31 adult patients with chronic hepatitis C. At the end of the first month with 1.5 MU of rIFN-alpha 2A, 9/31 (29%) had normal ALT values. Then, 22 patients were given 3 MU daily and at the second month 4 patients (18%) normalized ALT values. The 18 non-responders received 6 MU and 4 of them (22%) normalized ALT values (1 patient dropped out). Finally, the remaining 13 non-responders were given 9 MU and in 4 (30%) ALT fell to normal ranges. Three non-responders to 1.5 MU normalized ALT values when the dose of rIFN-alpha 2A was increased (n = 2, 3 MU; n = 1, 9 MU). The overall response achieved was 68%. Within 3 months after cessation of treatment, 12/20 (60%) responder patients had a relapse in ALT levels. Therefore, although daily administration of rIFN-alpha 2A does not improve the results obtained with a thrice-weekly schedule, a proportion of non-responders could benefit from an escalating dose to a high amount (63 MU/week) of rIFN-alpha 2A. PMID- 8445229 TI - Absence or delayed appearance of hepatitis B core antibody in chronic hepatitis B surface antigen carrier children. AB - An absence of the hepatitis B core antibody (anti-HBc) in hepatitis B surface antigen (HBsAg) carrier children has been reported before, but whether anti-HBc will ultimately appear is unknown. In a group of 420 HBsAg carrier children who were followed longitudinally, 10 (2.4%) had an absence or delayed appearance of serum anti-HBc. These 10 children were persistently seropositive for HBsAg, hepatitis B e-antigen, and hepatitis B virus DNA (HBV-DNA). Anti-HBc never appeared in 4, one of whom was a case of hepatitis B vaccine failure and became an HBsAg carrier. Three of the 4 were born to HBsAg carrier mothers. Liver biopsy in one revealed non-specific reactive hepatitis (NSRH). All 4 were asymptomatic during follow-up. Mothers of the other 6 children who had delayed appearance of anti-HBc were also HBsAg carriers. The children seroconverted to anti-HBc positivity between 2 and 8 years of age, and the titer of serum anti-HBc at the first appearance varied. There were no significant changes in liver function tests, HBV-DNA levels, or associated symptoms and signs before and after seroconversion. Liver biopsies were performed before anti-HBc seroconversion in 2 children and showed NSRH. All 10 children had a moderate to high replication of HBV as shown by the high titer of HBsAg and HBV-DNA. The absence of anti-HBc occurred almost exclusively in children who were infected perinatally.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8445230 TI - Structure-function relationship in secondary biliary cirrhosis in the rat. Stereologic and hemodynamic characterization of a model. AB - Secondary biliary cirrhosis in the rat is an attractive model since unlike other models it does not rely on exogenous toxic compounds to induce cirrhosis. However, because little is known about the microcirculatory abnormalities of this model, this study investigated hemodynamics in rats with predefined functional impairment and related them to different aspects of stereologically quantified structure. All animals with at least 50% reduction in microsomal function, assessed by the aminopyrine breath test, had portal hypertension. The sinusoidal space, as assessed by multiple indicator dilution in the perfused liver, was reduced whereas large vessel space was increased. This reduction in sinusoidal space could contribute to increased portal resistance. The degree of intrahepatic shunting varied as assessed by a microsphere technique (13.9 vs. 0.5% in controls). These alterations were confirmed by stereological analysis. Numerically, there was excellent agreement between functional indicator dilution data and anatomic quantitation. Microvascular exchange was impaired as in other models of cirrhosis as shown by a reduced extravascular albumin space (4.5 vs. 2.2%, p < 0.01). In contrast to alterations in vascular space, this functional impairment was not reflected in the stereologically assessed space of Disse which averaged 5% of liver volume in both groups. Finally, in spite of reduced microsomal function in vivo (aminopyrine breath test) and in vitro (aminopyrine N demethylase activity), the smooth endoplasmic reticulum was maintained (4.3 vs. 3.5 m2/ml cytosol, n.s.), which demonstrates that microsomal function in this model is reduced per unit hepatocyte. This suggests that the sick-cell hypothesis applies to secondary biliary cirrhosis in the rat. PMID- 8445231 TI - Oral pulse prednisone therapy after relapse of severe autoimmune chronic active hepatitis. A prospective randomized treatment trial evaluating clinical, biochemical, and lymphocyte subset responses. AB - To assess the efficacy of oral pulse prednisone therapy after relapse of severe autoimmune chronic active hepatitis and to determine the effects of such therapy on serum immunoglobulin G levels and peripheral blood lymphocyte subsets, 16 patients were randomized after relapse to therapy with prednisone 90 mg daily for 5 days each month or conventional daily dose therapy with prednisone in combination with azathioprine. Seven of the eight patients randomized to pulse therapy failed treatment after 1.9 +/- 0.7 months (range, 24 days to 6 months). Treatment failure occurred more commonly (87 vs. 0%, p < 0.01) and remission occurred less frequently (0 vs. 87%, p < 0.01) in patients receiving pulse therapy. The percentage and absolute numbers of circulating CD2 and CD4 cells decreased during relapse, while CD8 and CD20 cell counts were not significantly altered. Pulse therapy was associated with a significant increase in the percentage of CD4 cells and decrease in aminotransferase levels after 5 days. Serum immunoglobulin G levels, however, were not affected by treatment and after 1 month the biochemical findings and lymphocyte subsets were again similar to those at relapse. In contrast, serum immunoglobulin G levels decreased after 14 days of combination therapy and by 1 month the numbers in all lymphocyte subsets were higher than at relapse. We conclude that oral pulse prednisone therapy is ineffective for patients in relapse. The numbers of circulating CD2 and CD4 cells fall during relapse and increase as inflammatory activity subsides during corticosteroid therapy. Combination therapy reverses the biochemical changes and alterations in peripheral blood lymphocyte subsets that accompany relapse. PMID- 8445232 TI - Detection of hepatitis delta virus RNA in human liver tissue by non-radioactive in situ hybridization. AB - Several studies have demonstrated the presence of serum HDV-RNA by molecular hybridization in patients with chronic D infection, but there is scarce information about the presence of HDV-RNA in hepatic tissue. The presence of HDV RNA by in situ hybridization (ISH) with a non-radioactive probe in paraffin embedded hepatic tissue was studied in 29 patients with chronic delta hepatitis (20 with and 9 without intrahepatic delta antigen) and correlate their presence with the expression of hepatic delta antigen and serum HDV-RNA by dot-blot hybridization. HDV-RNA was detected by in situ hybridization in 18 cases: 16 of the 20 (80%) biopsies with intrahepatic delta antigen and 2 of the 9 (22%) without. HDV-RNA was not detected in any of the control cases. Serum HDV-RNA was found in 19 cases: 18 (90%) of 20 chronic delta hepatitis cases with tissular delta antigen and one of the 9 without intrahepatic delta antigen. All patients except one, who was positive for intrahepatic HDV-RNA, showed serum HDV-RNA. However, in two cases ISH detected hepatic HDV-RNA without tissular HDAg; one of these also had serum HDV-RNA and in the other positivity for hepatic HDV-RNA by ISH was the only marker of viral delta replication. In conclusion, detection of HDV-RNA in hepatic tissue by in situ hybridization with a digoxygenin-labelled probe is a rapid and sensitive method that could be a useful tool for diagnosis of HDV infection in clinical laboratories. PMID- 8445233 TI - Volumetric and functional liver blood flow are both increased in the human transplanted liver. AB - This study measured volumetric liver blood flow and galactose clearance concurrently during orthotopic liver transplant in human subjects. Ultrasound transit time flowmeters measured hepatic artery and portal vein flow 1-3 h after reperfusion. Galactose (100 mg/min) was infused over 45-60 min to steady state for calculation of clearance. Mean +/- S.D. total volumetric flow was 1966 +/- 831 ml/min with portal flow contributing 86%. Mean galactose clearance was 1988 +/- 641 ml/min. There was a significant correlation (p < 0.05, r = 0.61) between volumetric total liver blood flow and galactose clearance. The data show that: (i) the newly transplanted liver is capable of metabolizing galactose within 1-3 h of reperfusion; and (ii) liver blood flow is high in the newly implanted liver. The clinical importance of this observation is that there is increased clearance of high first pass substances by the transplanted liver which may be of importance in patient management. PMID- 8445235 TI - Comparison between wedge and needle biopsies for evaluating the degree of cirrhosis. AB - To examine whether the biopsy method could affect histological evaluation, the volumetric ratio of human liver parenchyma was estimated in specimens from subcapsular and intralobar areas, and also in specimens obtained by needle biopsy (Tru-Cut needle). A new method of morphometric analysis was performed using a computer-aided color image analyzer. Eighteen cirrhotic, 7 fibrotic, and 4 normal liver biopsies were taken during hepatic resection and analyzed. The parenchymal cell volume ratio in the intralobar area was significantly correlated with that in the subcapsular area, and less significantly with needle biopsy samples (r = 0.844, p < 0.001; r = 0.577, p < 0.01, respectively). Both showed one-to-one correspondence. These results suggest that both wedged and needle biopsy samples are appropriate for assessing the degree of fibrosis or cirrhosis, although the sampling variability of the latter is greater than the former. PMID- 8445234 TI - Re-evaluation of alpha-interferon treatment of chronic hepatitis B using polymerase chain reaction. AB - To re-evaluate the efficacy of 3 treatment trials involving 272 Chinese patients with chronic hepatitis B virus infection, serial serum samples were tested from 60 patients treated with alpha-interferon with or without prednisone priming and 12 control patients, who were negative for hepatitis B virus deoxyribonucleic acid using dot-blot hybridization. Serial samples were tested using nested polymerase chain reaction with primer sets chosen from the surface and core antigen coding regions. The 19 patients who did not show persistent serological change remained hepatitis B virus deoxyribonucleic acid positive using the polymerase chain reaction assay. Three of the 4 patients (75%) who lost hepatitis B surface antigen and 9 of 51 (17.6%) who lost hepatitis B e antigen became negative from 0 to 60 months after the e-seroconversion. All patients negative for the polymerase chain reaction assay had normal transaminase levels. Pooling the 3 trials together, 11 of 188 (5.9%) treated patients and 1 of 84 (1.2%) control patients became hepatitis B virus deoxyribonucleic acid negative. The difference was not statistically significant. As assayed by the polymerase chain reaction assay, patients who were treated with alpha-interferon with or without steroid priming and lost hepatitis B e antigen within 12 months were more likely to subsequently lose the virus completely from the serum (11 of 33) than those who lost hepatitis B e antigen after 12 months (none of 13; p = 0.029). PMID- 8445236 TI - Oral misoprostol or intravenous prostaglandin E2 do not improve renal function in patients with cirrhosis and ascites with hyponatremia or renal failure. AB - Prostaglandins play an important role in the maintenance of renal hemodynamics and water excretion in cirrhosis. To investigate whether the administration of prostaglandins improves renal function in cirrhotic patients with ascites, 16 patients with functional renal failure and/or dilutional hyponatremia were given oral misoprostol, a prostaglandin E1 analogue (200 micrograms/6 h for 4 days; n = 9) or intravenous prostaglandin E2 (0.5 microgram/min for 1 h followed by 1 microgram/min for another hour; n = 7). The administration of misoprostol did not induce significant changes in the glomerular filtration rate (59 +/- 11 vs. 54 +/ 11 ml/min), sodium excretion (4.0 +/- 1.3 vs. 4.1 +/- 2.1 microEq/min), and free water clearance (2.4 +/- 0.8 vs. 2.1 +/- 0.9 ml/min), nor did it improve the natriuretic response to an intravenous bolus of 40 mg of furosemide (486 +/- 124 vs. 406 +/- 88 microEq/min). Similarly, an infusion of prostaglandin E2 did not induce significant changes in the glomerular filtration rate (baseline: 33 +/- 6; 0.5 microgram/min: 31 +/- 5; 1 microgram/min: 31 +/- 6 ml/min) and sodium excretion (5.7 +/- 2.7; 3.2 +/- 1.4; and 1.5 +/- 0.7 microEq/min, respectively), whereas free water clearance decreased significantly (1.1 +/- 0.7; 0.5 +/- 0.5; and -0.1 +/- 0.2 ml/min, respectively, p < 0.05). These results indicate that oral misoprostol or the intravenous infusion of prostaglandin E2 do not improve renal function in cirrhosis with ascites. PMID- 8445237 TI - The results of a randomized double blind controlled trial evaluating malotilate in primary biliary cirrhosis. A European multicentre study group. AB - One hundred and one patients were included in a double-blind controlled trial to determine whether malotilate (diisopropyl 1,3-dithiol-2-ylidene malonate) is therapeutically effective in primary biliary cirrhosis. Fifty-two patients received malotilate (500 mg three times a day) and 49 patients placebo. The mean follow-up time was 28 months (range 6-46 months). The large majority of patients did not have advanced liver disease since only ten patients were in Child-Pugh class B and none in class C, and the median bilirubin and albumin at entry were normal. Malotilate had no clear effect on pruritus. In malotilate recipients the following statistically significant biochemical changes occurred: alkaline phosphatase decreased 21%, AST 20%, ALT 40%, IgA 12% and IgM 26%. In the placebo group no significant changes occurred. Evaluation of entry and 2-year liver biopsies indicated that malotilate diminished plasma cell and lymphocytic infiltrate and piece-meal necrosis, but had no effect on liver fibrosis. There was no difference in survival or in disease progression according to Child-Pugh criteria. In six patients receiving malotilate, but in none on placebo, treatment was discontinued due to suspected side effects. All patients recovered completely. We conclude that malotilate has an immune-modulating, anti inflammatory but not anti-fibrotic effect in primary biliary cirrhosis. The clinical relevance of the observed benefits, however, appears too slight to recommend malotilate as single drug therapy in primary biliary cirrhosis. PMID- 8445238 TI - Estradiol-17 beta-glucuronide-induced cholestasis. Effects of ursodeoxycholate-3 O-glucuronide and 3,7-disulfate. AB - The effect of the co-infusion of ursodeoxycholate and its taurine conjugate, 3-O glucuronide and 3,7-disulfate on estradiol-17 beta-glucuronide-induced cholestasis was examined. Estradiol-17 beta-glucuronide was intravenously administered to bile-drained rats at a rate of 0.075 mumol/min/100 g for 20 min. Co-infusion of ursodeoxycholate and its conjugates was simultaneously begun at a rate of 0.2 mumol/min/100 g and continued for 120 min. Ursodeoxycholate failed to improve and tauroursodeoxycholate only partially improved estradiol-17 beta glucuronide-induced cholestasis between 20 and 40 min, although both bile acids increased bile flow after 80 min. Tauroursodeoxycholate increased biliary estradiol-17 beta-glucuronide excretion. Ursodeoxycholate-3-O-glucuronide completely inhibited cholestasis induced by estradiol-17 beta-glucuronide without changing biliary estradiol-17 beta-glucuronide excretion. Although ursodeoxycholate-3,7-disulfate had only a minor effect on cholestasis, it increased biliary excretion of estradiol-17 beta-glucuronide. In the Eizai hyperbilirubinuria rat (EHBR), a hyperbilirubinemic mutant Sprague-Dawley rat, the same dose of estradiol-17 beta-glucuronide failed to induce cholestasis with a marked delay in biliary excretion of estradiol-17 beta-glucuronide. In summary, ursodeoxycholate-3-O-glucuronide is more effective than tauroursodeoxycholate in inhibiting estradiol-17 beta-glucuronide-induced cholestasis and ursodoexycholate 3,7-disulfate had little effect. However, the unexpected effects of ursodeoxycholate-3-O-glucuronide and 3,7-disulfate on excretion of estradiol-17 beta-glucuronide suggest that the interaction of these anions at the canalicular membrane is complicated, with interaction occurring at more than two pathways of the biliary excretion of these anions. PMID- 8445239 TI - Effects of organic anions and bile acids on biliary lipid excretion in hyperbilirubinemic mutant Sprague-Dawley rats. AB - The effects of organic anions and bile acids on biliary lipid excretion were studied in EHBR, a hyperbilirubinemic mutant Sprague-Dawley rat. A marked delay in the biliary excretion of BSP, cefpiramide, rose bengal and ursodeoxycholate disulfate was observed in these animals. The marked decrease in the biliary excretion of phospholipids and cholesterol and the uncoupling of biliary bile acids and lipids that occurred after the administration of BSP, cefpiramide and ursodeoxycholate-disulfate in control Sprague-Dawley rats was absent in EHBR. Rose bengal did not change biliary lipid excretion in either the control Sprague Dawley rats or the EHBR. Although taurocholate markedly increased bile flow and biliary bile acid excretion in both types of rats, the increase in biliary lipid excretion observed in the control Sprague-Dawley rats was absent in EHBR. These findings indicate that EHBR have an impairment of hepatic lipid transfer that is enhanced by bile acids, possibly at the level of intracellular vesicular lipid transport. PMID- 8445240 TI - HBeAg in the absence of HBsAg. PMID- 8445241 TI - The value of indirect immunofluorescence and solid phase techniques for ANCA detection. A report on the first phase of an international cooperative study on the standardization of ANCA assays. EEC/BCR Group for ANCA Assay Standardization. AB - This study describes the results of phase I of an international effort to develop and standardize assays for the detection of anti-neutrophil cytoplasmic antibodies (ANCA). 12 sera, four of which were selected for their potential to cause problems in the detection of various ANCA specificities, were analyzed in the standard indirect immunofluorescence (IIF) test and in ELISAs for ANCA routinely performed in the seven participating laboratories. The IIF methodology differed with respect to the dilution of the serum being screened and the concentration of the conjugate used. Results from sera with high ANCA titers were similar, although the quantitative values could not be compared. In sera containing rheumatoid factor and anti-nuclear antibodies (ANA), ANCA-unrelated staining patterns were observed. Six antigen preparations were used in ELISA for the detection of cANCA. In ELISA with purified proteinase-3 all three cANCA sera were positive, but not anti-myeloperoxidase (MPO) or anti-lactoferrin (LF) positive sera. The other assays were less sensitive or gave inconsistent results. Various preparations of purified MPO and LF used in ELISA were readily recognized by anti-MPO and anti-LF positive sera. From this study it can be concluded that the IIF test, although performed with different methods, shows comparable results using strongly positive sera. In general solid phase assays for cANCA detection are not well standardized and need improvement although the purified proteinase-3 ELISA is possibly an exception. MPO and LF can be used in ELISA procedures for the detection of pANCA-related antibodies. PMID- 8445242 TI - Liposome immunoassay (LIA) with antigen-coupled liposomes containing alkaline phosphatase. AB - Immunoliposomes were prepared and their immunoassay applications investigated. Liposomes were prepared from cholesterol and phospholipids including maleimidobenzoylphosphatidylethanolamine (MBPE) for conjunction with thiol containing antigens. Alkaline phosphatase (APase) was entrapped in the liposome and BSA, the antigen, was modified by reaction with 3-(2-pyridyl-dithio)propionyl N-hydroxysuccinimide ester (SPDP) to introduce thiol groups for efficient coupling. BSA-coupled liposomes (immunoliposomes) were incubated with anti-BSA serum, complement, and then with APase substrate. The amount of coupled BSA was affected by the reaction time, the composition of the liposome and the BSA concentration in the reactant. The amount of enzyme released from immunoliposomes as a final result of the immunoreaction increased with increasing concentrations of complement and antibody. The liposome immunoassay offers a relatively rapid and simple testing procedure to quantitatively or qualitatively determine the presence or absence of antibodies, or antigenic materials for diagnostic purposes. PMID- 8445243 TI - A new cell culture method (the lateral diffusion system) suitable for the induction of antibody-forming cells in vitro. AB - The lateral diffusion system (LDS) is a new cell culture method suitable for the in vitro induction of antibody-forming cells, based upon the diffusion of nutrients and other molecules between two contiguous compartments separated by a vertical microporous membrane. We compared an LDS cell culture plate with two commercially available diffusion culture units, the Marbrook chamber (C.A. Hendley Ltd.) and the Millicell-HA cell culture unit (Millipore Corporation), in terms of ability to support spleen cells responding to in vitro exposure to a soluble antigen (phosphorylcholine (PC) coupled to keyhole limpet haemocyanin) and two particulate antigens (a PC-rich microsomal fraction obtained from the parasite Trichinella spiralis, and sheep red blood cells). We found that, at high cell culture densities, similar numbers of plaque-forming cells were induced using the three units, but that the LDS is superior in versatility and ease of use to any of the devices currently used for PFC induction in vitro. PMID- 8445244 TI - Isolation of cytotoxic Kupffer cells by a modified enzymatic assay: a methodological study. AB - Kupffer cell (KC)-mediated cytotoxicity against tumor cells is of interest, since the liver is a major site of metastatic growth of primary colorectal cancer. KC isolation methods from rat livers, to study the tumoricidal properties of these cells, are based on perfusion of the liver and are therefore not suitable for human KC isolation from liver biopsies. In view of application to isolate KC from small wedge human liver biopsies, we have developed an isolation procedure for rat KC that does not require perfusion techniques. Liver tissue fragments were incubated with pronase with continuous pH registration and neutralization. KC were subsequently separated from other non-parenchymal cells by Nycodenz gradient centrifugation and purified by counterflow centrifugal elutriation. KC and other non-parenchymal cells were identified by immunophenotyping with a cytoplasmic monoclonal antibody ED1 and by ultrastructural analysis. About 3 x 10(6) KC per gram liver were isolated with a final purity of > 95% without loss of viability. To ensure that functionally competent KC were isolated, we assayed cytotoxicity against CC531 tumor cells in a recent developed cell-mediated MTT assay. Maximum cytotoxicity of KC was approximately 40% at an effector to target ratio of 10. In conclusion our approach seems to be a useful and simple method to isolate KC with good functional properties from rat livers, without the need for perfusion techniques. PMID- 8445245 TI - Purification of monoclonal antibodies from tissue culture medium depleted of IgG. AB - A method is described that allows rapid purification of IgG monoclonal antibodies from tissue culture supernatant; it is easy, relatively cheap and produces a product of high purity. Protein G linked to Sepharose fast flow gel has a high capacity for binding IgG and permits large volumes of supernatant to be loaded at high flow rates. However, Protein G cannot discriminate between the monoclonal antibody and other irrelevant IgG e.g. bovine IgG present in the tissue culture supernatant. Therefore, bovine IgG was removed from foetal calf serum by passage over protein G before being used as part of standard tissue culture medium. Hybridomas producing a rat anti-mouse (e.g. KT6) and a mouse anti-mouse (e.g. KJ23a) mAb were cultured in such tissue culture supernatant depleted of bovine IgG. Subsequent passage of the spent culture supernatants over protein G produced good yields of mAb of high purity and concentration. This method can been used to produce many different mAbs without the need for growing cells in a live host as ascites, or the need for specialised tissue culture media or expensive chromatography equipment. PMID- 8445246 TI - An automated micro-fluorometric assay for monitoring oxidative burst activity of phagocytes. AB - A micro-fluorometric assay using 2',7'-dichlorofluorescein diacetate (DCFH-DA) to monitor oxidative burst (OB) in phagocytes has been developed. This assay is based on the oxidation of nonfluorescent DCFH-DA to highly fluorescent 2',7' dichlorofluorescein (DCF) both intracellularly and extracellularly. A murine macrophage cell line, J774, and a human monocytic cell line, Mono Mac 6, were used as models. The cells were harvested from tissue culture flasks, washed, counted and adjusted to desired concentrations. They were then dispensed into a 96-well flat-bottom tissue culture plate. After adding DCFH-DA and an agent eliciting OB, the plates were incubated in 5% CO2 at 37 degrees C for various periods. The intensity of fluorescence was measured directly in the wells of the tissue culture plate with the cells in situ using a computerized microplate fluorometer at 485 nm excitation and 530 nm emission. This assay provided a rapid measurement of oxidative burst of phagocytes. The automated micro-fluorometric assay may be suitable for screening the immunomodulating activities of various biological and pharmacological substances. PMID- 8445247 TI - A simple optical fiber device for quantitative fluorescence microscopy of single living cells. AB - A simple and relatively inexpensive system is described for obtaining quantitative fluorescence measurements on single living cells loaded with a fluorescent probe to study cell physiological processes. The light emitted from the fluorescent cells is captured by and transported through an optical fiber. After passage through appropriate filters the light is measured using a photomultiplier tube. The optical fiber is mounted in one of the microscope outlets. Signals derived from the photomultiplier are converted to voltage, amplified, and displayed on a recorder. In the excitation pathway a shutter control unit is mounted. With this control unit the period that the excitation pathway is 'opened' and 'closed' can be adjusted, to reduce cell damage and/or bleaching of the probe. This option allows time-lapse recording of experiments up to 1 h. We have used this set-up with a single and dual emission fluorescent probe to determine intracellular calcium concentrations and pH, respectively. In Fluo-3-loaded K562 target cells bound to natural killer cells, a temporary rise in [Ca2+]i was accompanied by bleb formation. The simple construction of this set up is interchangeable between different types of fluorescence microscopes and can easily be combined with other microscopy techniques, e.g., patch clamp. PMID- 8445248 TI - Application of polymer beta-cyclodextrin-treated fetal calf serum to in vitro antibody production. AB - In order to induce an optimal plaque-forming cell response to sheep red blood cells (anti-SRBC PFC response) in vitro, murine splenocytes have been cultured in RPMI 1640 medium containing 10% fetal calf serum (FCS). In this paper, we report that 10% intact FCS in such a conventional medium can be replaced by 2% modified FCS which has been exposed to insoluble polymer beta-cyclodextrin (CD). The most efficient procedure of treatment of FCS was an incubation of 1/50 diluted FCS with 20 mg/ml polymer beta-CD for 3.5 h at 20 degrees C. The PFC response supported by 2% polymer beta-CD-treated FCS, was the same as that obtained when mixing 10% FCS, and was completely dependent on the existence of antigen (SRBC) and enhanced by 2-mercaptoethanol. The time-course profiles of the PFC responses induced in both cultures were almost the same. The 2% polymer beta-CD-treated FCS containing medium was also effective in inducing both a primary PFC response to the T cell-independent antigen (trinitrophenyl-lipopolysaccharide) and a polyclonal PFC response stimulated by lipopolysaccharide. Inactive FCS lots (so called deficient lots) also became fully supportive at 2% after treatment with polymer beta-CD. These results indicate that polymer beta-CD-treated FCS is not economical for supporting antibody production, but also useful for those experiments on isolation and analysis of factors derived from cultured lymphocytes. PMID- 8445249 TI - Quantitative analysis of interleukin-2-induced proliferation in the presence of inhibitors using a mathematical model. AB - The proliferative response of CTLL-2 cells to human recombinant interleukin-2 (IL 2) can be modeled mathematically using enzyme kinetic equations. This approach has been used to analyze dose-response curves (IL-2 concentration vs. level of proliferation) measured by MTT and [3H]TdR assays. The values of functional dissociation constants, equivalent to IL-2 concentrations giving 50% of the maximal response, depended on the cell concentration and increased from 4 to 60 pM for the [3H]TdR assay and from 40 to 140 pM for the MTT assay when the cell concentration was increased from 2 x 10(3) to 4 x 10(4) cells/well. The types of inhibition and dissociation constants for various inhibitors of IL-2-dependent proliferation such as mAbs against IL-2 receptor (7D4 and AMT13) and normal mouse serum (NMS) were also analyzed. Both mAbs exhibited competitive mechanisms of inhibition whereas NMS inhibited IL-2-driven proliferation in a mixed manner. Two gel-filtration fractions of NMS with inhibitory activity manifested different types of inhibition: purely competitive type of inhibition in the case of a 10-15 kDa fraction and a mixed type of inhibition for a 100-150 kDa fraction. The proposed model can also be used for quantitative analysis of the influence of various factors (pH, temperature, cultivation condition) on the level of proliferation. PMID- 8445250 TI - Simultaneous evaluation of phagocytosis and Fc gamma R-mediated oxidative burst in human monocytes by a simple flow cytometry method. AB - In this study we describe a fast, simple, and objective flow cytometry method to quantify simultaneously phagocytosis and Fc gamma R-mediated oxidative burst in human monocytes. Peripheral blood monocytes isolated by elutriation were sequentially incubated with 2',7'-dichlorofluorescein-diacetate (DCFH-DA) and sheep erythrocytes opsonized with rabbit IgG (SRBC-IgG), and then analysed by flow cytometry. Two parameters were studied simultaneously in the same cell population: forward scatter modifications (grade of phagocytosis) and fluorescence intensity of DCFH oxidation (index of oxidative burst). We found a statistically significant correlation (r = 0.96274) between the forward scatter increase and the amount of phagocytosis as determined by light microscopy. We also found a significant correlation between the oxidative burst and phagocytosis studied both microscopically (r = 0.7714) and by flow cytometry (r = 0.78056). As the presence of DCFH did not impair monocyte phagocytosis, we conclude that this simple method could be a useful tool in functional studies of monocytes. PMID- 8445251 TI - Covalent linking of haptens, proteins and nucleic acids to a modified polystyrene support. AB - Biological molecules of various molecular weights were successfully linked to polystyrene microtitration plates bearing carbonyl and hydroxyl reactive groups. Cross-linking of proteins, nucleic acids and haptens was carried out with water soluble carbodiimide. The covalent nature of the binding reaction was demonstrated by the immunodetection of a hapten linked to the surface through a disulphide spacer arm and its subsequent release by cleavage of the bridge. The amount of protein fixed per surface unit could be correlated to molecular weight. Nanograms of biotinylated nucleic acids and synthetic polynucleotides could also be retained on the solid support. PMID- 8445252 TI - Optimizing follicular dendritic cell isolation by discontinuous gradient centrifugation and use of the magnetic cell sorter (MACS). AB - Follicular dendritic cells (FDC) contribute minimally to the total cell population of lymphatic tissue. In order to obtain higher numbers of viable FDC with only a small fraction of contaminating cells the following procedure was developed. Subsequent to the usual mechanical and enzymatical digestion of human tonsils, single cells were layered on top of a discontinuous bovine albumin gradient and centrifuged at 8500 x g. The suspension collected from the 1.052 1.030 interphase contained an average of 10.5% FDC. Next, the preparation was subjected to a new step involving separation of FDC previously treated with biotin-labelled KiM4 monoclonal antibody, raised against FDC, and attached via biotin-streptavidin bonding to streptavidin-conjugated paramagnetic beads. Purification on a magnetic cell sorter (MACS) yielded 3.3-10.1 x 10(6) cells with an average FDC content of 78.4%. The viability and morphology of the resulting FDC population was examined using trypan blue staining or electron microscopy. This technique will permit in vitro studies and long term cultures with FDC isolated from human lymphatic tissue. PMID- 8445253 TI - Detection of intracellular cytokines by flow cytometry. AB - During the last years it has become increasingly clear that production of most cytokines is not confined to one cell type. Thus, a method to detect cytokines at the single cell level would be a helpful tool to study the contribution of different cells to cytokine production in heterogeneous cell populations. Recently, Sander et al. (1991) demonstrated that it is possible to detect intracellular cytokines by fixation with paraformaldehyde, permeabilization with saponin and subsequent indirect immunofluorescent staining using fluorescence microscopy. Here, we describe a modified method to increase the specific intracellular staining which enables us to detect IFN-gamma, IL-2 and IL-4 producing cells by single laser flow cytometry. The carboxylic ionophore monensin was used to interrupt intracellular transport processes leading to an accumulation of the cytokine in the Golgi complex. This resulting increase of the signal/noise ratio permitted us to detect weakly fluorescent cells such as IL-4 producing cells. While IL-4 was detected in approximately 1-3% of peripheral mononuclear cells from healthy donors, up to 30% of the cells produced IFN-gamma and nearly 50% IL-2 after phorbol ester and ionomycin stimulation. Microscopic and flow cytometric analysis showed a highly significant correlation. Using three color flow cytometry it was possible to measure intracellular cytokines and cell surface markers simultaneously. Subpopulations of human T cells (e.g., CD4+ CD45R0-) producing a restricted cytokine pattern could be identified by cell surface staining and were characterized by their cytokine production. Consequently, there was no further need for cell sorting to determine cytokine producing subsets in heterogeneous cell populations. We have tested human T cell clones for intracellular cytokine production and found a high concordance to ELISA analysis of the supernatants. We conclude that detection of intracellular cytokines by flow cytometry is a rapid, easy and semiquantitative assay which may be used to study individual cells in heterogeneous populations as well as to screen homogeneous cells for their cytokine pattern. This method is particularly relevant in view of the accumulating evidence of the functional role that subsets of (T) cells may play in various diseases depending on the pattern of cytokines they produce. PMID- 8445254 TI - A novel ELISA assay for the detection of C3 nephritic factor. AB - We have developed an ELISA procedure for the detection of C3 nephritic factor (C3NeF), in which wells are coated with a fixed concentration of 2 micrograms C3b per well, and subsequently reacted with B and D. The presence of increasing concentrations of NiCl2 showed a NiCl2 concentration-dependent generation of C3bBb and very little solid-phase bound C3bBb was generated with MgCl2. The formation of solid-phase C3bBb in the presence of an optimal concentration of 1 mM NiCl2, was time-dependent and plateau values were reached after 30 min at 37 degrees C. IgG purified from the serum of a patient with membranoproliferative glomerulonephritis (MPGN) type II containing C3NeF stabilizing activity was bound to the C3bBb generated on microwells in a dose-dependent manner whereas normal IgG exhibited only minor reactivity. C3NeF activity was measured using the ELISA method in patients with MPGN type II (n = 15) and other diseases (n = 17) and in normal controls (n = 15). Most of the patients with MPGN type II exhibited positive C3NeF at various levels, while two of the disease controls showed only slight reactivities. C3NeF titers measured by this new ELISA procedure correlated well with previously described hemolytic assays (r = 0.617, p < 0.01). PMID- 8445255 TI - Nanogram quantitation of secreted protein in a recombinant yeast fermentation using an immuno-ligand assay. AB - A liquid-phase immuno-ligand assay has been developed for quantitative determination of recombinant tick anticoagulant protein (rTAP) secreted in yeast fermentations. A polyclonal anti-TAP antibody was labeled with biotin or fluorescein. Labelled antibodies were used in a non-competitive sandwich format to capture rTAP from solution, then reacted with urease-conjugated anti fluorescein antibody. Detection of the immune complex was by a commercially available silicon-based potentiometric sensor which measures urease activity. Sample throughput was 90 samples per 7 h with a 2 h incubation time. The range of the standard curve was 0.1-10 ng/ml with an assay sensitivity of 0.025 ng/ml. For a mid-range concentration of 1 ng/ml, intraday and interday method precision was determined to be 1.031 +/- 0.061 and 1.077 +/- 0.026 ng/ml, respectively. Typically, spiked samples of 1 microgram rTAP/ml fermentation medium required dilutions of 1/1000 to generate a response in the mid-range of the standard curve. This assay provides a convenient method to quantitate product expression in multiple fermentation samples within 3 h after sampling. In addition, a modified version of the assay was developed which provided accurate results within 1 h of sample acquisition. PMID- 8445256 TI - A colorimetric assay to evaluate the immune reactivity of blood platelets based on the reduction of a tetrazolium salt. AB - Since the first report in 1983, blood platelet reactivity from patients with immediate hypersensitivity reactions, and particularly allergic asthma and aspirin-sensitive asthma, has been evaluated by the release of cytotoxic mediators able to induce the death of parasite larvae, and by the generation of oxygen derived free radicals, measurable by chemiluminescence. We demonstrate here that platelets are able to reduce MTT tetrazolium salt proportionally to the stimulation level in two models of platelet triggering, one IgE-dependent and one aspirin-dependent. This method correlated significantly with the cytotoxicity assay of platelet stimulation (r = 0.965, p < 10(-5) for IgE-dependent stimulation; r = 0.723, p < 10(-4) for aspirin-dependent stimulation). The MTT colorimetric assay should complement or possibly replace previous methods of assessing platelet activation which were of limited use allowing broader investigations on the involvement of platelets in immune processes and in allergic or pseudoallergic reactions. PMID- 8445258 TI - The use of recombinant human growth hormone for radioiodination and standard preparation in radioimmunoassay. AB - Recombinant human growth hormone (rec-hGH) obtained by cloning hGH precursor gene, bacterial expression and periplasmic secretion of the authentic, mature form of the hormone was used, after purification and characterization, for the preparation of radioimmunoassay (RIA) reagents. 125I-rec-hGH was prepared by the classical chloramine-T iodination technique, while an internal standard of the same rec-hGH was used and calibrated against pituitary hGH reference preparation (NIDDK-hGH-RP-1) with the use of a reference antiserum (NIDDK-anti-hGH-2). In both cases the behavior of the recombinant preparation was identical to that of the pituitary hormone. This confirms previous data on bacterial correct processing and folding of the protein, as far as its immunological behavior is concerned and indicates its suitability for the preparation of immunoassay reagents. PMID- 8445257 TI - Immunochemical characterization of anti-H monoclonal antibodies obtained from a mouse immunized with human saliva. AB - Three IgM class anti-H monoclonal antibodies (1E3, 1E5 and 3H1) were obtained from a BALB/c mouse immunized with human O type saliva. These antibodies were found to agglutinate red cells from O group and A and B subgroups but not from Bombay and para-Bombay individuals whose H antigen was barely detected by anti-H reagents. The agglutination reactions of these antibodies were inhibited by H antigens from human tissues. It was also demonstrated that both 1E3 and 3H1 reacted with H disaccharide (Fuc alpha 1-->2Gal beta), H type 1 (Fuc alpha 1- >2Gal beta 1-->3GlcNAc beta), H type 2 (Fuc alpha 1-->2Gal beta 1-->4GlcNAc beta), H type 3 (Fuc alpha 1-->2Gal beta 1-->3GalNAc alpha) and H type 4 (Fuc alpha 1-->2Gal beta 1-->3GalNAc beta) but not with Lea (Gal beta 1-->3[Fuc alpha 1-->4]GlcNAc beta), Leb (Fuc alpha 1-->2Gal beta 1-->3[Fuc alpha 1-->4]GlcNAc beta), X (Gal beta 1-->4[Fuc alpha-->3]GlcNAc beta) or Y (Fuc alpha 1-->2Gal beta 1-->4[Fuc alpha 1-->3]GlcNAc beta). On the other hand, 1E5 was found to react with H type 1, H type 2, Leb and Y. Because of the unique reactivities against various fucosyl linkages these monoclonal antibodies could be useful not only as anti-H reagents but also as reagents for the structural analysis of fucosylated glycoconjugates. PMID- 8445259 TI - Splenic implantation of nitrocellulose pellets as a means of raising antibodies to nanogram quantities of antigen. PMID- 8445260 TI - Measurement of antibody binding to antigenic peptides conjugated in situ to albumin-coated microtitre plates. AB - Monoclonal antibodies have been prepared against a synthetic peptide with a sequence corresponding to a repeated hydrophilic region of the protein core of the human MUC-2 gastrointestinal mucin. Peptide conjugates, prepared by glutaraldehyde cross-linking with keyhole limpet haemocyanin (KLH) and bovine serum albumin (BSA), were employed as the immunogen and target antigen (for screening by ELISA), respectively. However, for the measurement of antibody binding to peptide by an ELISA procedure, an alternative strategy was developed and is described in this report: peptides were conjugated directly to BSA immobilized by physical adsorption to the surface of microtitre plate wells. This procedure permits peptides to be tested as target antigens by ELISA without prior preparation of peptide-carrier conjugates. PMID- 8445261 TI - Use of an enzyme-linked immunosorbent assay (ELISA) to measure the expression of the K88 fimbrial antigen by enterotoxigenic Escherichia coli (ETEC). AB - A solid-phase enzyme-linked immunosorbent assay (ELISA) has been developed to detect and quantify the K88 fimbrial adhesin antigen. The assay was used to detect cell-bound antigen present in bacterial suspensions and cell-free K88 antigen present in extracts. Comparable amounts of K88 antigen were detected with whole bacteria and in the equivalent extracts. The assay was used to compare the expression of the K88 antigen by one laboratory strain (K12:K88ab) and three wild type strains (O8:K87:K88ab:H19, O8:K87:K88ac:H19 and K88ad) of enterotoxigenic Escherichia coli (ETEC) during cultivation with eight medium types and two medium forms. Determination of the expression of K88 during unshaken batch culture revealed a correlation between growth phase and expression, with maximal concentrations being detected during late log to early stationary phase. Colony blotting experiments demonstrated that expression of the K88 antigen was under quantitative and not qualitative control. PMID- 8445262 TI - Autologous lymphocytes prevent the death of monocytes in culture and promote, as do GM-CSF, IL-3 and M-CSF, their differentiation into macrophages. AB - Blood monocytes collected by apheresis from healthy donors were differentiated in vitro to macrophages which were subsequently activated with recombinant human interferon-gamma. 7 day cultures were established by seeding Ficoll-separated mononuclear cells or elutriation-purified monocytes under different culture conditions. The best macrophage yields required the seeding of mononuclear cells (instead of purified monocytes) in teflon bags with a high air-liquid surface interface. The effects of GM-CSF, IL-3 and M-CSF on the macrophage yield were then evaluated. GM-CSF increased the average yield by 3.6- and 2.3-fold when purified monocytes or total mononuclear cells were seeded respectively. The corresponding increases with IL-3 were 2.5- and 2.1-fold respectively and with M CSF 1.2- and 1.4-fold respectively. Macrophages matured under these various conditions displayed similar CD14, CD64, CD71, HLA-DR and Max 1 antigen expression and similar in vitro anti-tumoral activity against U937 cells. Culturing in the presence of cytokines permits the large scale production of activated macrophages for adoptive immunotherapy trials. PMID- 8445263 TI - Long term preservation of indirect immunofluorescent specimens in ultralow freezer (-75 degrees C) PMID- 8445265 TI - Quantitative immunoassays for type II collagen and its cyanogen bromide peptides. AB - This paper describes the development of quantitative immunoassays utilizing mouse monoclonal antibodies which are monospecific to type II collagen. The monoclonal antibodies were characterized and tested extensively for reactivity against a panel of antigens including actin, myoglobin, thyroglobulin, ssDNA, tetanus toxin and different types of collagens including their CnBr-derived peptides. Four monoclonal antibodies having strict monospecificity to type II collagen were selected. Quantitative immunoassays developed with these antibodies can measure either type II collagen in its native conformation or type II collagen-derived cyanogen bromide peptides. The assay conditions such as coating concentration of antigen, monoclonal antibody concentration, second antibody concentration and incubation times were optimized to obtain maximum possible sensitivity. These quantitative immunoassays can be employed to measure type II collagen or type II collagen-derived peptides in low amounts ranging from 20 to 100 ng/ml. The assays can be applied to chondrocyte cultures without interference from serum components or other collagen types. PMID- 8445264 TI - Use of particulate forms of protein antigens to increase the sensitivity of antigen-specific proliferation assays. AB - Different forms of recombinant HIV-1 gp160 and tetanus toxoid were adsorbed onto latex microspheres and this particulate form of the proteins was used to measure antigen-specific proliferation in vaccinated rhesus macaques. Proliferative responses to proteins bound to microspheres were significantly greater and allowed for the detection of antigen-specific responses that were not detected using soluble proteins. The responses were antigen-specific and required prior immunization of the animals. Additionally, the presence and magnitude of the proliferative responses was associated with antibody responses to the same proteins suggesting the results were representative of in vivo responses and that the assay format did not induce in vitro artifacts. PMID- 8445266 TI - Isolation of a protein complex from purulent sputum consisting of proteinase-3 and alpha 1-antitrypsin reactive with anti neutrophil cytoplasmic antibodies. AB - The detection of ANCA (anti-neutrophil cytoplasmic antibodies) is of importance in the diagnosis of Wegener's granulomatosis (WG) and solid-phase assays for the detection of c-ANCA have been set up by various groups, using purified proteinase 3 (PR-3) in an ELISA or RIA. For the isolation of PR-3 large numbers of PMNs are needed. We therefore examined the possibility of isolating PR-3 from the purulent sputum of patients with chronic bronchitis or cystic fibrosis, since large numbers of PMNs and their degranulation products are present in such material. By a three-step chromatographic procedure (4-phenylbutylamine affinity chromatography, Biorex 70 cation exchange chromatography and monoclonal antibody anti-PR-3 affinity chromatography) we isolated a 53 kDa protein that was recognized on immunoblot by MoAbs directed against PR-3 and alpha 1-antitrypsin (alpha 1AT). We show that the 53 kDa protein is a complex of PR-3 and alpha 1AT. This complex is reactive with a selected set of c-ANCA positive sera from patients with Wegener's granulomatosis. PMID- 8445267 TI - Optimization of the L-M cell bioassay for quantitating tumor necrosis factor alpha in serum and plasma. AB - In attempting to quantitate TNF-alpha in body fluids using current bioassay protocols, we discovered several factors which adversely affect reliability, sensitivity and specificity. The objective of this study was to establish an optimum assay for use with serum and plasma samples. While adopting the commonly used L-M cell bioassay to test serum and plasma samples, we noted non-specific staining of cell debris and protein by crystal violet dye, even if the wells were washed prior to staining. However, when we replaced crystal violet with tetrazolium salts to measure cell viability, we discovered that both serum and plasma, from a variety of species, non-specifically reduced both MTT and XTT tetrazolium salts to a colored formazan product resulting in absorbance values significantly higher than those of medium and serum controls. This effect was particularly pronounced with fetal bovine serum which showed significant color development with as little as 6% serum in the test wells. Maximum sensitivity can only be obtained by eliminating these false negative readings. Therefore the serum or plasma containing supernatant must be removed from the test wells and replaced with fresh serum-free medium prior to addition of the substrate. This finding should be applicable to other body fluids such as urine, milk, and synovial fluid as well as any tetrazolium based assay for cell viability which uses serum-supplemented culture medium. Additionally, when the substrate XTT, which reduces to a water-soluble formazan product, was compared to MTT which reduces to a water-insoluble product, XTT was found to be superior since elimination of the solubilization process resulted in reduction of assay time. Also, overall absorbance readings using XTT were higher than with MTT, without any loss of sensitivity. There were no differences in detectability of TNF-alpha between serum and plasma and use of preservative-free heparin was found not to have adverse effect on TNF-alpha assay. Heat treatment of both serum and plasma seemed to inactivate factors that contributed to the non-specific lysis of the L M cells when their concentrations exceeded 25%. PMID- 8445269 TI - Stereotactic localization and resection of intracranial tumors. AB - Stereotaxis has existed since the early 1900s, originating in Western Europe. Its practice was originally limited to isolation of nerve tracts, drainage of superficial abscesses and early attempts at psychosurgery. Today, with stereotactic-compatible imaging techniques and equipment, many types of intracranial lesions can be precisely localized and resected. Stereotactic approaches to therapy, including aggressive surgical resection, have become the treatments of choice for many types of potentially devastating lesions. A case study illustrates a stereotactic resection procedure, as well as the nursing plan of care and implications for the neuroscience nurse. PMID- 8445268 TI - Rapid analysis of leukocyte-endothelial adhesion. AB - Neutrophil adherence to endothelial monolayers in multi-well plates can be rapidly quantitated, using a fluorescent plate reader. The number of adherent neutrophils which have been labeled with biscarboxyethyl carboxyfluorescein (BCECF) was calculated by comparing fluorescence of endothelial monolayers to a reference standard curve determined by fluorescence intensity of suspensions of labeled neutrophils. The limit of sensitivity approached 100 cells, which is similar to that achieved by the most sensitive of alternate techniques. The assay, after isolation of the neutrophils, can be completed in 1.5 h. The ability to utilize microwell plates permits the use of large numbers of samples. This method has the advantage of being relatively simple and rapid while maintaining a sensitivity comparable to alternate approaches which employ radioactive labeling or counting of adherent or non-adherent cells. PMID- 8445270 TI - Learning needs of persons with epilepsy: a comparison of perceptions of persons with epilepsy, nurses and physicians. AB - The purpose of this study was to describe and compare patients', nurses' and physicians' perceptions of learning needs of persons with epilepsy. The study is based on adult learning theory which states that learning needs dictate receptivity to information and knowledge of learning needs can help structure teaching sessions. Study participants were recruited from patients attending epilepsy clinics, neuroscience nurses employed at study hospitals or working with neurologists or neurosurgeons and neurologists or neurosurgeons practicing in the state. The sample sizes were: 59 patients, 85 nurses and 38 physicians. Data were analyzed using frequencies, percent and analysis of variance. Data analysis revealed that patients, nurses and physicians similarly ranked major areas of learning needs. However, differences in the ranking of individual learning needs were noted between patients and health care providers. An understanding of the differences and similarities among the groups provides useful information for educational programs for epilepsy patients. PMID- 8445271 TI - Adaptation six months after multiple trauma: a pilot study. AB - This pilot study investigated the functional and psychosocial adaptation of 18 survivors of multiple trauma who were in the home setting 6 months after discharge from a tertiary trauma center. Seventeen subjects reported complete functional independence and one reported the need for assistance with self-care activities as measured by the Modified Barthel Index. All subjects reported problems with psychosocial adaptation as measured by the Psychosocial Adjustment to Illness Scale (PAIS). Subjects with high PAIS scores (worst adaptation) reported problems in all domains of the PAIS, whereas those with low PAIS scores (best adaptation) reported most problems in health care orientation. Mann-Whitney U tests were significant for gender, household composition and employment status when compared with low PAIS scores (p < 0.05). An analysis of variance confirmed employment status was the best predictive factor for low PAIS scores. PMID- 8445272 TI - Endovascular therapy of neurovascular malformations. AB - The development of microcatheters and newer embolytic agents has made it possible to treat persons with arteriovenous malformations, arteriovenous fistulas and aneurysms. Until recently, endovascular embolization was usually performed to devascularize tumors prior to surgical removal. The growing number of neurovascular conditions that can be treated by endovascular embolization has led to the need for neuroscience nurses to be knowledgeable about indications, materials, methods, risks, patient preparation and nursing implications in the care, education and discharge planning for the embolization patient. PMID- 8445273 TI - Multidisciplinary approach to managing acute head injuries. PMID- 8445274 TI - Nursing concerns associated with radical skull base surgery: a case study. AB - Historically, surgical management of extensive neoplasms of the cranial base has been limited by anatomical boundaries. However, major theoretical and technological advances now permit radical surgical resections. The perioperative nursing care of these patients is challenging and requires a wealth of knowledge and skills. The complexity of caring for patients undergoing radical skull base surgery is highlighted through a case study. PMID- 8445275 TI - Using conceptual frameworks or models to guide nursing research. AB - To be useful, a frame of reference must enable an investigator to organize all components of a research study beginning with the literature review and problem statement and continuing through interpretation of findings. Careful conceptualization of the entire research process will move nurses closer to building an orderly system of scientific knowledge in which each investigation serves as a tool of nursing science. PMID- 8445276 TI - A case study of two methods of administering phenytoin enterally and the subsequent serum phenytoin levels in head-injured patients. PMID- 8445277 TI - Connections and meanings. PMID- 8445278 TI - Neuroleptic malignant syndrome: a dangerous complication of neuroleptic therapy. AB - Neuroleptic malignant syndrome is a potentially fatal syndrome that can occur in patients taking neuroleptics or other psychotropic drugs. It is characterized by muscle rigidity, hyperthermia, altered mentation, autonomic dysfunction, increased CPK and leukocytosis. A primary factor in NMS may be a decrease in functioning of dopaminergic neurons. Treatment usually consists of discontinuation of the neuroleptic drug, drug therapy with bromocriptine and dantrolene and supportive measures. The key to successful medical and nursing management is aggressive supportive care with a focus on preventing complications. With the frequency of administration of neuroleptic drugs, neuroscience nurses should be aware of this potentially lethal complication of neuroleptic therapy. PMID- 8445280 TI - [Proceedings of the 66th annual meeting of the Japanese Orthopaedic Association. Abstracts]. PMID- 8445279 TI - Revised epilepsy stressor inventory. AB - The relationship between high levels of stress and the occurrence of seizures has been postulated, and findings from studies are beginning to substantiate this hypothesis. Identifying stressors experienced by each person will help health care workers in developing plans of care. In the original epilepsy stressor inventory (ESI) persons selected stressors they had experienced that were associated with epilepsy. To facilitate congruency of the ESI with the Lazarus Transactional Stress Model, revisions were made that allow the person to rate the degree of stressfulness the stressor causes. An alpha of .93 was found indicating high internal consistency of the revised epilepsy stressor inventory (ESI-R). A test-retest reliability of .76 was found. Because the ESI-R is short (22 items) and easy to administer, it can be readily used in practice settings. PMID- 8445281 TI - Steps toward improved safety of treatment in hemophilia B. PMID- 8445282 TI - Cell-cell interactions in the generation of eicosanoids: charting the routes and products of transcellular biosynthesis. PMID- 8445283 TI - Regional versus systemic modulation of the microcirculation in diabetes mellitus. PMID- 8445284 TI - Acquired abnormalities of von Willebrand factor: facts to consider in patients with unexpected bleeding. PMID- 8445285 TI - Purified Aspergillus proteins: going where no one has gone before. PMID- 8445286 TI - Antibody-mediated platelet activation. PMID- 8445287 TI - Factor VIII inhibitors: a continuing problem. PMID- 8445288 TI - Human coagulation factor IX: assessment of thrombogenicity in animal models and viral safety. AB - Thromboembolic complications associated with prothrombin complex concentrate treatment may be related to the high levels of factors II and X in these products. We report here results from preclinical safety studies with a human coagulation factor IX product (AlphaNine; Alpha Therapeutic Corp., Los Angeles, Calif.) that contains no detectable factor II or VII and less than 10 units of factor X/100 units of factor IX. This product was manufactured from virally inactivated factor IX complex with a barium citrate adsorption step followed by affinity chromatography yielding factor IX concentrate with a specific activity of about 86 factor IX units/mg protein. Electrophoresis and immunoblot analysis indicated that the factor IX represents about 65% of the protein in this product. The virus inactivation step incorporated into the manufacturing process (incubation with n-heptane at 60 degrees C for 20 hours) was shown to inactivate at least 8.6 logs of type 1 human immunodeficiency virus. The barium citrate adsorption and affinity chromatography steps were found to remove 2.0 logs of the marker virus, vaccinia, and the DEAE ion-exchange chromatography used to produce factor IX complex was found to remove 1.4 logs of the marker virus, Sindbis. Analysis of three separate manufacturing lots with the polymerase chain reaction revealed no evidence of hepatitis C virus. The purified factor IX was nonthrombogenic when tested at doses of 450 units/kilogram in a rabbit stasis (Wessler) model, whereas the prothrombin complex concentrates were found to be thrombogenic at doses of less than 50 units/kg. There was no evidence of DIC in a porcine model after infusion of 200 units/kg of coagulation factor IX, as manifested by negative fibrin monomer tests, the absence of fibrin in blood vessels at autopsy, little or no change in prothrombin times and partial thromboplastin times, and only moderate decreases in platelet levels after infusion. PMID- 8445289 TI - Effect of selective inhibition of thromboxane synthesis on renal function in diabetic nephropathy. AB - Studies of nondiabetic renal disease suggest that thromboxane may be an important mediator of abnormal renal function. The role of thromboxane in diabetic nephropathy is not fully understood. We measured in a double-blind, randomized, placebo-controlled crossover study the effect of a thromboxane synthase inhibitor (FCE 22178, 400 mg two or three times per day) on urinary excretion of thromboxane B2 and 6-keto-prostaglandin F1 alpha, glomerular filtration rate (measured as clearance of polyfructosan), effective renal plasma flow (clearance of para-aminohippuric acid), fractional clearances of albumin and immunoglobin G and the reabsorption rate of beta 2-microglobulin in 15 patients with type 1 (insulin-dependent) diabetic nephropathy. In seven additional patients, the effect of the thromboxane synthase inhibitor given as 400 mg twice per day was compared with that of the thromboxane synthase inhibitor given as 400 mg three times per day. FCE 22178 administration caused a significant inhibition in the excretion of urinary thromboxane B2 and 2,3-dinor-thromboxane B2 compared with placebo (12.3 +/- 2.1 vs 24.6 +/- 5.1 ng/gm creatinine, p = 0.006, and 78.5 +/- 20.3 vs 335.5 +/- 84.1 ng/gm creatinine, p = 0.004, respectively) without any compensatory increase of 6-keto- prostaglandin F1 alpha or 2,3-dinor-6-keto prostaglandin F1 alpha that reflect prostacyclin I2 biosynthesis. Glomerular filtration rate, effective renal plasma flow, renal vascular resistance, and filtration fraction were not significantly different after placebo or thromboxane synthase inhibitor treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8445290 TI - Autoantibody to von Willebrand factor in systemic lupus erythematosus. AB - A 17-year old woman (patient 1) was found to have severe bleeding as the initial manifestation of systemic lupus erythematosus. Profound deficiencies of factor VIII coagulation activity (10%), von Willebrand factor (vWF) antigen (< 10%), and ristocetin cofactor (< 1%), and a disproportionate loss of large molecular weight multimers of vWF were observed. An antibody to vWF was suspected, and an enzyme linked immunoadsorbent assay (ELISA) was devised to detect and quantify such antibody. The ELISA measured the binding of anti-vWF antibody from sample plasma to surface-bound vWF antigen. Binding was detected by a conjugate of alkaline phosphatase with affinity-purified anti-human immunoglobulin G, A, or M and a chromogenic substrate for alkaline phosphatase. Controls included plasma from normal subjects, from patients with von Willebrand's disease, and from a patient (patient 2) with type III von Willebrand's disease who had developed an inhibitor to vWF. Analysis of our patient's plasma revealed immunoglobulin G, A, and M anti vWF antibodies. Preincubation of the plasma from patient 1 and patient 2 with pure vWF antigen completely inhibited antibody binding, confirming antibody specificity. These antibodies were quantitatively titered by determining the volume ratio of normal pooled plasma (a source of vWF antigen) to test plasma required to inhibit 50% of the antibody binding to immobilized vWF antigen. The value was 0.8 +/- 0.3 (mean +/- SD of three determinations) for the immunoglobulin G of our patient as compared with 15.6 +/- 2.9 for the immunoglobulin G of patient 2. The titers of the immunoglobulin A and M were less than 0.05.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8445291 TI - Production and characterization of a monoclonal antibody to a major concanavalin A--nonbinding antigen of Aspergillus fumigatus. AB - A hybridoma secreting immunoglobulin G1 antibody was produced against Aspergillus fumigatus. In this study we used interleukin-4 as a growth factor to augment the survival and multiplication of immunoglobulin G1-secreting hybridomas. The antigen recognized by this monoclonal antibody is a low-molecular weight concanavalin A-nonbinding component of A. fumigatus. The monoclonal antibody affinity-purified antigen showed specific reactivity with serum from patients with allergic bronchopulmonary aspergillosis, whereas all allergic asthmatic patients with skin-test reactivity to A. fumigatus demonstrated only low levels of antibodies similar to those in normal control subjects. This antigen failed to show cross-reactivity with other fungal antigens. These results indicate that this monoclonal antibody can be used for the purification of specific antigens useful in the immunodiagnosis of allergic bronchopulmonary aspergillosis. PMID- 8445292 TI - In vitro evaluation of factor VIII--bypassing activity of activated prothrombin complex concentrate, prothrombin complex concentrate, and factor VIIa in the plasma of patients with factor VIII inhibitors: thrombin generation test in the presence of collagen-activated platelets. AB - Clinical efficacy of plasma-derived products with factor VIII--bypassing activity in patients with factor VIII inhibitors is difficult to evaluate. It is also difficult to predict efficacy by coagulation assay. A test of thrombin generation in defibrinated plasma and in the presence of activated platelets was used to test the bypassing activity of the most currently used products (activated prothrombin complex concentrate from various origins, prothrombin complex concentrate, and factor VIIa). The bypassing activity was evaluated in the absence and presence of tissue factor. In plasma with inhibitor, activated prothrombin complex concentrate elicited dose-dependent thrombin formation, whereas prothrombin complex concentrate and factor VIIa induced only minimal thrombin activity. Addition of tissue factor in the assay elicited thrombin generation in the presence of factor VIIa and prothrombin complex concentrate and allowed additional thrombin formation in the presence of activated prothrombin complex concentrate. Although it is hazardous to extend results of in vitro testing to clinical efficacy, our study sheds some light on the mechanism of action of the various substances used to treat bleeding episodes in patients with factor VIII inhibitors. PMID- 8445293 TI - Effect of citric acid and maltol on the accumulation of aluminum in rat brain and bone. AB - Deposition of aluminum in the body is responsible for the development of dialysis related diseases in patients with renal dysfunction and may play a role in the development of certain neurodegenerative disorders. Although citric acid is known to be a strong enhancer of gastrointestinal absorption of aluminum, its effect on aluminum distribution and accumulation is not yet clear. Maltol has been shown to increase the neurotoxicity of aluminum, but little is known about its effect on aluminum deposition in the body. To elucidate the role of citric acid and maltol in aluminum accumulation and toxicity, rats were loaded intraperitoneally during a 7-day period with different amounts of aluminum chloride in absence or presence of citric acid or maltol before analysis of aluminum in serum, brain, bone, and urine. Coadministration of citric acid led to relatively reduced serum levels, as compared with aluminum and aluminum-maltol treatment. This is explained by both tissue elimination and enhanced renal elimination. Only at the highest aluminum dose (8 mg/kg body weight) was an enhancing effect of citric acid on accumulation of aluminum in brain observed; no effect on bone aluminum was seen. Furthermore, it was seen that citric acid alters the distribution pattern of aluminum. This may be explained by the postulation of a characteristic aluminum citrate species in serum. Administration of citric acid may increase this aluminum fraction in serum, thereby inducing an alteration of the distribution pattern. Maltol was shown to be a strong enhancer of aluminum accumulation in serum, brain, and bone. The rise of aluminum in these target tissues was dose dependent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8445294 TI - Characterization of radioimmunoassays for high- and low-molecular weight urokinases and estimation of different molecular forms of urokinase in urine and plasma. AB - Antibody populations against high- and low-molecular weight urokinases (HUK and LUK) were purified by passage of rabbit antiserum immunoglobulin fractions made against HUK and LUK through HUK- or LUK-bound Sepharose 4B (Pharmacia AB, Uppsala, Sweden) gels, respectively. Radioimmunoassays were then set up with these antibody populations. The characteristics of these radioimmunoassays were studied by competition of different antigens against radiolabeled HUK or LUK for these antibodies. We found that the anti-HUK antibody population recognizes epitopes on the light chain of HUK, most of which are situated outside of the urokinase-receptor binding sequence of amino acids. The anti-LUK antibody population probably recognizes a region on LUK distinct from its catalytic site. This region is also present in HUK but is altered in single-chain urokinase, suggesting that a conformation change takes place when single-chain urokinase is converted to HUK. The complexes of HUK and LUK with plasminogen activator inhibitor 1 or 2 could compete in either radioimmunoassay, with different and diminished efficiencies. Taking advantage of this result, we devised a procedure to measure the concentrations of various urokinase species in human urine. We found that freshly voided urine contained substantial amounts of free HUK, some HUK- and LUK-plasminogen activator inhibitor complexes, and a small amount of single-chain urokinase. By using a combination of radioimmunoassay and zymography, we found that human plasma contains mostly HUK-plasminogen activator inhibitor 1 complexes, a small amount of single-chain urokinase or HUK, and no LUK or LUK-inhibitor complexes. PMID- 8445295 TI - A novel approach for introducing hepatocytes into the portal circulation. AB - Many attempts have been made to treat metabolic diseases of the liver. One approach, called ex vivo gene therapy, is based on correcting the genetic defect in the patient's hepatocytes. In this model, the liver is resected and hepatocytes are isolated, plated in culture, and genetically corrected with recombinant retroviruses. The cells are then harvested and infused into the portal circulation, where they seed in the sinusoids of the liver. In this study, a canine model was used to develop an approach to ex vivo gene therapy that requires only one surgical procedure. The basic concept is to place a catheter in the mesenteric circulation at the time of liver resection that can be used subsequently to deliver hepatocytes into the liver. With four 18 to 28 kg mongrel dogs, a laparotomy was performed, the left lateral segment of the liver was resected, and a 9.5 Fr Hickman catheter was introduced into the inferior mesenteric vein. At 10 days, the catheter was studied angiographically and removed. The catheter remained patent and was easily removed without untoward effects. A subsequent necropsy was performed to evaluate the consequences of this procedure. There was no hematoma at the site of the catheter placement or evidence for intraportal clot. This approach has been used in subsequent studies to treat a patient with familial hypercholesterolemia. PMID- 8445296 TI - Development of storage granules during megakaryocyte maturation: accumulation of adenine nucleotides and the capacity for serotonin sequestration. AB - The specific release of platelet-dense body constituents such as adenine nucleotides and serotonin has a fundamental role in hemostasis. The content of adenine nucleotides in platelet dense bodies is probably established in megakaryocytes, but very little is known about this process. To gain a better understanding of platelet development, we studied the storage and metabolic pools of adenine nucleotides and the capacity for serotonin sequestration in storage granules during megakaryocyte maturation. Megakaryocytes were isolated from guinea pig bone marrow and separated in subgroups at different phases of maturation. The sequestration of adenine nucleotides and serotonin in storage granules was assessed by using calcium ionophore to induce secretion under nonlytic conditions, and metabolic pool adenine nucleotides were evaluated by using digitonin under controlled lysis conditions. The study showed that there were similar amounts of cytoplasmic adenosine triphosphate (ATP) in the mature and immature fractions based on digitonin-induced controlled lysis (1.26 +/- 0.37 nmol/microgram phosphorus vs 1.23 +/- 0.44 nmol/microgram phosphorus). However, only the mature cells contained a significant amount of storage pool ATP (0.41 +/ 0.19 nmol/microgram phosphorus vs 0.05 +/- 0.05 nmol/microgram phosphorus) released in response to A23187. The subgroups of megakaryocytes contained equal amounts of total adenosine diphosphate (ADP) extractable with ethanol (0.49 +/- 0.14 nmol/microgram phosphorus vs 0.55 +/- 0.50 nmol/microgram phosphorus) but only mature cells contained ADP in the storage granules (0.25 +/- 0.13 nmol/microgram phosphorus vs 0.07 +/- 0.05 nmol/microgram phosphorus).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8445297 TI - Red blood cell calcium level is elevated in women: enhanced calcium influx by estrogens. AB - Red blood cell (RBC) calcium level had been found to be higher in women than in men. This study was designed to evaluate whether this is a general phenomenon and to elucidate a possible mechanism for a gender-related difference in RBC calcium levels. Differences in RBC calcium levels between women and men were examined in normal subjects, in patients with chronic renal failure (CRF) who were known to have elevated RBC calcium levels, and in female and male rats. RBC calcium level was higher in healthy women (6.1 +/- 0.5 mumol/L in women vs 4.4 +/- 0.3 mumol/L in men; p < 0.01), in women with CRF (45.8 +/- 11.8 mumol/L vs 15.4 +/- 1.1 mumol/L in men with CRF; p < 0.025) and women undergoing hemodialysis treatment (43.4 +/- 4.7 mumol/L vs 8.8 +/- 0.9 mumol/L in men undergoing hemodialysis p < 0.001). RBC calcium levels in female rats were also significantly higher than those in male rats. Ovariectomy reduced RBC calcium levels in female rats to those of male rats, whereas castration of male rats had no effect on RBC calcium levels. These in vivo findings suggest that the elevated RBC calcium level is associated with activity of female sex hormones. To investigate a possible mechanism, the in vitro effect of beta-estradiol on calcium 45 influx into RBCs and its effect on basal and calmodulin-stimulated Ca adenosine triphosphatase (CaATPase) activity in RBC membranes was determined. CaATPase activity was not affected by beta-estradiol at various concentrations and different incubation periods.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8445298 TI - Recognition and sequestration of young and old erythrocytes from young and elderly human donors: in vitro studies. AB - Experiments were performed to determine the mechanism of recognition for sequestration of erythrocytes from elderly and young donors and to study in vitro a previously observed shortening of in vivo life span of erythrocytes in elderly donors. Erythrocytes from young and elderly human donors were separated according to their age-density on Stractan gradients. Elderly donors had more low age density erythrocytes than did young donors. Erythrocytes from elderly donors had higher levels of immunoglobulin G (IgG) on their erythrocytes than did those from young donors. In an in vitro erythrophagocytosis assay, young (low age-density) and old (high age-density) erythrocytes from elderly donors and old but not young erythrocytes from young donors were recognized and sequestered. Phagocytosis of erythrocytes from elderly and young donors can be specifically blocked by beta galactoside but not alpha-galactoside sugars. This phagocytosis is not blocked by protein G, which specifically blocks Fc-gamma-mediated erythrophagocytosis, thus demonstrating that the recognition of the senescent erythrocyte is not due to the direct recognition of a physiologic autoantibody. beta-Galactoside and alpha galactoside sugars have no inhibitory effect on erythrophagocytosis mediated by IgG anti-Rh-D antibodies. Erythrophagocytosis of young and old erythrocytes from elderly donors and old erythrocytes from young donors are all mediated by a macrophage receptor with lectin-like properties, which can be inhibited by a beta galactoside-like sugar moiety, and not by an Fc receptor that recognizes erythrocyte-bound IgG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8445299 TI - Effect of tracheal insufflation of deferoxamine on acute ozone toxicity in rats. AB - To test the hypothesis that deferoxamine (DFO) may protect the lung against the acute toxicity of ozone (O3), male Sprague-Dawley rats (250 to 300 gm) were tracheally insufflated before exposure to O3 (2 ppm for 4 hours) with DFO (25 mg/kg), ferric-DFO, or sterile water. Measurements of bronchoalveolar lavage fluid (BALF) protein, ascorbate, hydrogen peroxide, and lipid hydroperoxides were made immediately after O3 exposure and 12 and 24 hours later. DFO (25 mg/kg) decreased BALF protein concentration (p < 0.05) and was associated with higher BALF ascorbate concentrations (p < 0.01) in O3-exposed animals. Ferric-DFO did not show these protective effects. No peroxides were found in BALF from any control or O3-exposed animals (detection limit: H2O2, 1 pmol; lipid hydroperoxides, 0.3 pmol). Higher DFO doses (50 mg/kg and 100 mg/kg) did not decrease BALF protein concentration immediately after O3 exposure or 12 hours later. Indeed, the highest dose was toxic to O3-exposed animals. Although DFO is able to protect against O3-induced lung damage in rats, apparently by chelating iron, its effect dose range appears to be narrow. PMID- 8445300 TI - Coronary microvascular fluid flux and permeability: influence of angiotensin II, aldosterone, and acute arterial hypertension. AB - Vascular permeability of the coronary and mesenteric circulation is increased in association with the arterial hypertension that accompanies either endogenous activation of the renin-angiotensin-aldosterone system (RAAS) or exogenous administration of angiotensin II (AII). Whether this occurs as a result of increased intravascular pressure or of elevations in plasma concentrations of AII or aldosterone (ALDO) (or both) is unclear. This acute study of filtration independent coronary fluid exchange and macromolecular permeability was undertaken to address these issues in open-chest, anesthetized dogs. The influence of arterial hypertension, with or without associated elevations in plasma AII or ALDO (or both), on coronary permeability was examined by monitoring the response in cardiac lymph flow, protein concentration, and capillary and intramural coronary artery structure. Experimental groups received a 90-minute intravenous infusion of either AII (n = 8), methoxamine (MX; n = 7), or ALDO plus MX (n = 5) in equipotent doses that raised arterial pressure to comparable levels. When we compared these animals with normotensive, instrumented controls (n = 5), we found that (1) lymph flow was a function of arterial and microvascular pressures in each group; (2) increased protein permeability, myocardial edema, extravasated red cells, and infused colloidal carbon were found in both ventricles with AII, together with endothelial discontinuities and enhanced abluminal capillary endothelial vesicle formation, when plasma ALDO had risen significantly in response to AII; and (3) macromolecular permeability was no different from that in controls after MX or ALDO plus MX. Based on this short term study of acute arterial hypertension, we would conclude that acute elevations in microvascular pressure increase fluid flux, whereas increased circulating effector hormones of the RAAS, not plasma ALDO or hypertension alone, alter coronary microvascular structure and permeability to macromolecules Responsible mechanisms remain to be defined. PMID- 8445301 TI - The aims of middle ear surgery to improve hearing. PMID- 8445302 TI - The cellular mechanism of ossicular erosion in chronic suppurative otitis media. AB - This is the first report of the application of a new examination technique for the assessment of cellular activity during bone resorption in chronic suppurative otitis media (CSOM). A total of nineteen includes removed during the course of tympanomastoid surgery were studied (retraction pocket: 2; tubo-tympanic CSOM: 4; attico-antral CSOM: 13). The microscopic surface topography of each specimen was examined using the scanning electron microscopy (SEM), and the appearances are interpreted in terms of cortical cellular activity. The results suggest that the mechanism of ossicular erosion in CSOM is similar regardless of the exact type of disease. Extensively pitted areas were seen in all specimens. These pits are morphologically indistinguishable from those characteristic of osteoclastic activity (Howship's lacunae). We conclude that in all causes the surface topography of eroded incudes is consistent with the activity of osteoclasts. PMID- 8445303 TI - The value of head dressings for middle ear surgery. AB - A prospective trial was performed to ascertain the value of head dressings in the post-operative management of patients undergoing middle ear and mastoid surgery. One hundred consecutive patients were randomly allocated to a head dressing or no head dressing group after wound closure. Nine patients in the head dressing group developed a wound complication as opposed to four patients in the no head dressing group. The application of a pressure dressing following middle ear and mastoid surgery is unnecessary and may contribute to increased wound morbidity. PMID- 8445304 TI - The need for and development of a single use disposable nasal spray. AB - Nasal sprays, which work on the Venturi principle, have the disadvantage of suck back which makes them unhygienic for use in more than one patient. In Wrexham we have developed a disposable nasal spray system, which is safe and would be of benefit to other ENT departments. PMID- 8445305 TI - Nasal muco-ciliary clearance in snuff users. AB - The inhalation of nasal snuff (powdered tobacco) is widely prevalent in the Indian sub-continent. The effect of snuff application on the nasal mucociliary clearance (NMMC) time has been suspected but not demonstrated before. In this study the saccharin test is used to demonstrate the rate of nasal mucociliary clearance among chronic snuff users. The study demonstrates the depressant action of snuff on the nasal mucociliary clearance rate. A pharmacological and pathological basis for the depressant action of snuff on the NMMC rate is hypothesised on the basis of the results obtained. PMID- 8445306 TI - Prolonged and recurrent tonsillitis associated with sexually transmitted Chlamydia trachomatis. AB - Chlamydia trachomatis is a common sexually transmitted pathogen. We describe six cases of tonsillitis associated with sexually transmitted C. trachomatis infection. The organism was isolated from tonsillar crypts in all patients, and from uro-genital swabs in five of the six patients. In three partners of the patients, C. trachomatis infection of the uro-genital organ was assessed. They all had a history of orogenital sexual intercourse prior to the illness. PMID- 8445307 TI - Cefotaxime prophylaxis in major non-contaminated head and neck surgery: one-day vs. seven-day therapy. AB - Patients who undergo major surgery of head and neck benefit from perioperative antibiotic prophylaxis. This study was developed to determine if seven days of antibiotic administration would be more effective than one day. A prospective randomized double blind study was designed. Patients were randomly assigned to receive cefotaxime sodium for either 24 hours or seven days. In each case, the drug was administered intramuscularly, beginning one to two hours pre-operatively and continued for the prescribed period. Sixty patients were included in the trial. Of 30 patients assigned to one day of perioperative prophylaxis, wound infection developed in four (13 per cent). Of 30 patients assigned to seven days of perioperative antibiotic prophylaxis, wound infection developed in three (10 per cent) (P > 0.05). These data suggest that no beneficial effect from administration of antibiotics for longer than 24 hours post-operatively can be achieved in patients who undergo major head and neck surgery. PMID- 8445308 TI - Knot to be condemned. AB - It is common practice following mastoid and middle ear surgery to apply a pressure bandage to the ear for a short post-operative period to reduce local swelling. The bandage is usually secured in such a way as to lift it away from the eye, sometimes with a length of ribbon gauze tied in a knot over the temporal region. Pressure from the knot may cause injury to the underlying tissues leading to post-operative complications which hitherto have not been described. PMID- 8445309 TI - Suction polypectomy forceps. PMID- 8445310 TI - Familial stapes superstructure fixation. AB - Congenital stapes superstructure fixation was found in a mother in both ears and her daughter in one ear. The head of the stapes was fixed to the pyramid by a bony bar which lay immediately superior to a normal stapedius muscle. Removal of the bony bar resulted in normal hearing, which has been maintained. We believe that these are the first reported cases of this abnormality. PMID- 8445311 TI - Bilateral auricular pseudocyst: a case report and discussion. AB - Pseudocyst is a rare, often misdiagnosed condition affecting the pinna. A case of bilateral pseudocyst is reported and the recent literature discussed with respect to aetiology and treatment. PMID- 8445312 TI - Comparison of methods of evaluating hearing benefit of middle ear surgery. AB - The objective of this paper is to compare two methods of predicting the level of subjective patient benefit following reconstructive middle ear surgery. This should have always been an important consideration in advising patients regarding surgery, but assumes even more relevance in these days of clinical audit and cost benefit analysis. The two methods studied were the '15/30 dB rule of thumb' (Smyth and Patterson, 1985) and the 'Glasgow plot' (Browning et al., 1991). The predictions of benefit for each of the two methods were compared to the assessment of actual benefits by the patient post-operatively. The results of this comparison in 153 patients were analysed, the rule of thumb was found to be somewhat more sensitive in predicting patient benefit. PMID- 8445313 TI - Bilateral carcinomas of the maxillary sinus. AB - We report a 68-year-old male with a rare case of synchronous bilateral carcinomas of the maxillary sinus. A CT scan revealed a large tumour mass that extruded from the left maxillary sinus; tissue of soft density filled the right antrum which had intact bony walls. A probe antrostomy on the right side disclosed a tumour which was diagnosed histologically as the same poorly differentiated squamous cell carcinoma as that in the left antrum. The incidence and aetiology of this disorder are presented, and its diagnosis and management are discussed. PMID- 8445314 TI - Idiopathic spontaneous tonsillar haemorrhage. AB - Since the advent of antibiotics major spontaneous tonsillar haemorrhage is extremely rare. The causes are usually ascribed to vessel wall erosion secondary to bacterial infection or infectious mononucleosis. We report the case of a 20 year-old female, presenting to the ENT department with tonsillar bleeding in the absence of any identifiable infective or traumatic process. PMID- 8445315 TI - Post laryngectomy diverticulum--a case report. AB - A case of a pharyngeal diverticulum complicating a total laryngectomy is presented. Possible aetiology and management are discussed. PMID- 8445316 TI - Two simultaneously occurring hypopharyngo-oesophageal diverticula. AB - We report a case of two simultaneously occurring hypopharyngeal-oesophageal diverticula, one apparently originating above, the other below the cricopharyngeal muscle. The radiological and clinical findings of this rare condition are presented. PMID- 8445317 TI - Fatal massive upper respiratory tract haemorrhage: an unusual complication of localized amyloidosis of the larynx. AB - Localized amyloidosis of the larynx is usually described as a non-bleeding lesion. We report a patient with localized laryngeal amyloidosis who developed a massive upper respiratory tract haemorrhage and died. This potentially fatal complication of localized amyloidosis of the larynx merits recognition as the disease could be controlled in most instances by surgical excision of the amyloid deposit. PMID- 8445318 TI - Recurrent laryngeal nerve palsy secondary to massive venous thrombosis. AB - Retrospective review of all patients with recurrent laryngeal nerve palsy seen at a comprehensive cancer centre over a 30 month period has revealed three patients with this diagnosis apparently related to massive venous thrombosis. All three patients had an underlying diagnosis of malignancy (two colon, one breast) and an indwelling central venous access device with its tip in the superior vena cava. Direct laryngoscopy was otherwise normal in all patients, and two had normal CT scans of the neck and mediastinum. This third patient had mediastinal adenopathy, but this was unchanged from the previous nine months. Although two patients expired shortly after this presentation, the other patient lived for one year and his palsy resolved with the resolution of his superior vena cava syndrome. Mediastinal inflammation secondary to the thrombophlebitis may be the direct cause of this unusual presentation. PMID- 8445319 TI - Histoplasmosis of the oral cavity, oropharynx and larynx. AB - A patient with oropharyngolaryngeal histoplasmosis is presented. He has been treated for disseminated tuberculosis (TB) for 10 months, with no improvement. Repeat biopsy of a tongue ulcer, together with a swab of the ulcer base, confirmed the presence of Histoplasma capsulatum. Treatment with amphotericin B resulted in a rapid recovery. PMID- 8445320 TI - A clinical, genetic and audiological study of patients and families with bilateral acoustic neurofibromatosis. AB - The neurofibromatoses consist of at least two distinct autosomal dominant hereditary disorders. Neurofibromatosis type 1 (NF1) is due to a lesion on chromosome 17q. Neurofibromatosis type 2 (NF2) is caused by a defect on chromosome 22q. The hallmark of NF2 is the development, in the second and third decades, of bilateral acoustic neuromas. NF1 is characterized by the appearance of cafe-au-lait spots and neurofibromas in addition to iris hamartomas, or Lisch nodules, of the eye, during the first and second decades. Ten families were personally studied. A total of 16 members were found to be affected with NF2. A protocol for evaluation and review of subjects and relatives of NF2 families is proposed. A team approach, coordinating the expertise of multiple specialties is recommended. PMID- 8445321 TI - Penicillamine-induced changes in elastic tissue of the upper respiratory tract. AB - We describe a patient who developed upper respiratory tract symptoms following long-term treatment of Wilson's disease with penicillamine. These symptoms were attributed to areas of pharyngeal thickening and were treated with a laser. Histological examination of the lesions showed proliferations of abnormal elastic fibres similar to those previously described at other sites, especially the skin, in patients receiving penicillamine. This drug impairs the maturation and reduces the stability of elastic fibres and although elastic tissue throughout the body is affected, we are aware of no previous reports of penicillamine-induced changes presenting with upper respiratory tract symptoms. PMID- 8445322 TI - Ultrasonography in laryngeal cancers. AB - Endolaryngeal spread of laryngeal malignant tumours is usually determined by conventional endoscopy; however, it can not measure the outward extension of the tumour. As an alternative method for assessing the extension of a tumour and detecting metastatic lymph nodes, we have introduced high-resolution ultrasonography (US) in 34 patients with laryngeal epidermoid carcinoma. The ultrasonographic results were compared with the clinical, operative and histological findings. The ultrasonography revealed malignant extensions in the thyroid cartilage in nine cases, in the carotid artery in four cases, and in the thyroid gland in five cases. These were confirmed by surgical and histopathological examinations. Six patients out of the 34 were subclinical cases, who had metastatic lymph nodes, which were diagnosed by US only. In this study US had a sensitivity of 94.44 per cent and a specificity of 93.75 per cent. The sensitivity and specificity of palpation of the cervical lymph nodes were 66.66 per cent and 87.55 per cent respectively. It may be concluded that high resolution real-time US is a sensitive, simple and inexpensive method for evaluating laryngeal cancers and subclinical cervical lymph node metastasis. PMID- 8445323 TI - Malignant oncocytoma of the parotid gland: a case report with an immunohistochemical and ultrastructural study. AB - A rare case of a 71-year-old man with malignant oncocytoma is presented. The tumour was found in the left parotid region with enlarged lymph nodes in the neck. The resected parotid mass consisted of three discrete nodules, each histologically characterized by a uniform proliferation of oncocytic tumour cells. The patient underwent repeated operations for recurrences and metastases, and eventually died of acute pneumonia 18 months after the first admission. Metastases to the lymph nodes, ribs, spine and liver had been clinically pointed out. Immunohistochemically, the tumour cells were positive for alpha-1 antitrypsin, alpha-1-antichymotrypsin, lactoferrin, secretory component and carcinoembryonic antigen (CEA), while they were negative for S-100 protein and HHF35 (muscle specific actin). Ultrastructural pictures disclosed numerous mitochondria in the cytoplasm of the tumour cells, revealing neither myofibrils nor secretory granules. These findings therefore support the concept that this tumour is of a glandular epithelial origin. PMID- 8445324 TI - Ossifying fibromyxoid tumour (of soft parts) of the head and neck: a clinicopathological and immunohistochemical study of nine cases. AB - Ossifying fibromyxoid tumour (OFT) is a recently described, mesenchymal neoplasm originally defined as a borderline or low-grade malignant lesion. Prior reports of OFT characterize it as a slow growing lesion with a propensity to occur in both the upper and lower extremities. Most OFTs have occurred within the deep subcutis or skeletal muscle. We report nine cases which arose in the head and neck region. Six of the nine tumours were classified as ossifying variants of OFT while two were non-ossifying variants that lacked a discernable shell of lamellar bone. One tumour was classified as a malignant OFT. Seven lesions occurred in a subcutaneous site while two lesions occurred intraorally beneath the gingival and palatal mucosa. The OFTs occurred in six men and three women (age range of 29-75 years). The tumours had histological features compatible with previously described OFTs and consisted of lobulated nests of small, cytologically bland round cells (with the exception of one malignant OFT), with a myxoid to hyalinized stroma and were surrounded in part by dense fibrous connective tissue. Six cases had an incomplete rim of lamellar bone with occasional perpendicularly oriented spicules of bone. Five lesions were immunostained. S-100 protein, neuron specific enolase, and Leu-7 were found in three out of five tumours. Glial fibrillary acidic protein, smooth muscle actin (SMA), and muscle specific actin (MSA) were detected in two out of five lesions, although staining for SMA and MSA was weak in reactivity. Staining for vimentin was strongly positive in all five cases tested. The tumours were not reactive with antibodies directed against cytokeratin, epithelial membrane antigen or neurofilament protein. Follow-up information, available in eight cases, revealed multiple local recurrences in the one tumour believed to be a malignant OFT. The histogenesis of these tumours is uncertain, although the preponderance of evidence suggests a Schwann cell origin. PMID- 8445325 TI - Characterization of interleukin-1 and interleukin-6 production by hepatic endothelial cells and macrophages. AB - Interleukin-1 (IL-1) and interleukin-6 (IL-6) derived from Kupffer cells are major inducers of hepatic inflammation and the acute phase response. The present studies demonstrate that liver endothelial cells also produce significant quantities of IL-1 and IL-6, suggesting that these cells also participate in these processes. Endothelial cells and macrophages were isolated from female Sprague-Dawley rats by combined collagenase and pronase perfusion of the liver followed by centrifugal elutriation. In the absence of stimulation, endothelial cells were found to spontaneously produce IL-1 and IL-6 in a time-dependent manner, reaching maximal levels after 10 h in culture for IL-1 and 6-8 h for IL 6. The amount and kinetics of cytokine production by hepatic endothelial cells were similar to those observed with Kupffer cells. In further studies, the effects of lipopolysaccharide (LPS), a potent liver macrophage activator and inflammatory agent, on cytokine release were analyzed. Treatment of rats with LPS resulted in a decrease in IL-1 release by both cell types compared to cells from untreated animals. In contrast, LPS treatment had no major effect on IL-6 release. We also found that both macrophages and endothelial cells could be induced to produce additional IL-1 and IL-6 by treatment with LPS in vitro, but only if they were preincubated for at least 24 h prior to stimulation with LPS and analyzed for cytokine release. These data demonstrate that liver endothelial cells, like Kupffer cells, have the capacity to produce immunoregulatory and proinflammatory cytokines. PMID- 8445326 TI - Inhibition of tumor cell mitochondrial respiration by macrophage cytotoxic mediators distinct from interferon-gamma. AB - Macrophage-mediated inhibition of mitochondrial respiration in EMT-6 murine mammary adenocarcinoma cells can be mimicked in vitro by treatment of the cells with interferon-gamma (IFN-gamma) in combination with tumor necrosis factor, interleukin-1, or lipopolysaccharide. Conditioned supernatants obtained from activated macrophages appear to contain interferon-gamma, suggesting that inhibition of mitochondrial respiration in tumor cells was caused by synergy of IFN-gamma with other cytokines. To further characterize monokines that cause inhibition of mitochondrial respiration in tumor cells, EA13.5 macrophage-like cells were isolated and selected for inhibition of mitochondrial respiration in EMT-6 tumor cells. After stimulation with IFN-gamma and lipopolysaccharide, the EA13.5 cells released into conditioned supernatants a cytotoxic mediator that induced nitric oxide synthesis and caused lesions in the electron transport chain of EMT-6 cells similar to the lesions caused by activated peritoneal macrophages. Enzyme-linked immunosorbent assay demonstrated that the conditioned supernatants produced by EA13.5 macrophage cells did not contain IFN-gamma. Treatment of the EA13.5 cell-conditioned supernatants with neutralizing antibody against IFN-gamma did not abrogate the inhibition of mitochondrial respiration in EMT-6 cells caused by these conditioned supernatants. This study demonstrated that unidentified macrophage cytotoxic mediators distinct from IFN-gamma are involved in the induction of nitric oxide synthesis and inhibition of mitochondrial respiration in tumor cells. PMID- 8445327 TI - Inhibition of Corynebacterium parvum-primed and lipopolysaccharide-induced hepatic necrosis in rats by selective depletion of neutrophils using a monoclonal antibody. AB - To examine whether neutrophils are involved in the pathogenesis of experimental liver dysfunction, we observed the effect of selective in vivo neutrophil depletion by a monoclonal antibody (RP-3) on the pathogenesis of acute experimental hepatic necrosis in rats induced by a preparative injection of heat killed Corynebacterium parvum and a challenging dose of lipopolysaccharide (LPS) (positive control group). The serum transaminase titer 8 h after LPS injection was reduced by selective depletion of peripheral blood neutrophils as a result of RP-3 treatment (RP-3 group). A kinetic study showed that the serum transaminase titer of the RP-3 group was significantly lower than that of the positive control group from 4 to 24 h after LPS injection. The transaminase level was significantly lower in the group with less than 400/mm3 peripheral blood neutrophils than in the group with a greater number. The effect of RP-3 on the transaminase level was due neither to the injection of cancer ascites nor to RP-3 injection with the accompanying decrease in complement titer. These results suggest that neutrophils play an important role in the induction of liver dysfunction in this system. PMID- 8445328 TI - Endogenous nitric oxide inhibits the synthesis of cyclooxygenase products and interleukin-6 by rat Kupffer cells. AB - Macrophage production of nitric oxide (.N = O) leads to considerable alterations of vital metabolic pathways in various target cells. The present study tested whether .N = O synthesis by Kupffer cells (KCs), the resident macrophages of the liver, interferes with the secretory function of these cells. As in other macrophage-type cells, the combination of lipopolysaccharide (LPS) and interferon gamma (IFN-gamma) was a potent stimulus of .N = O synthesis by KC. Treatment with LPS and IFN-gamma also induced significant production of prostaglandin E2 (PGE2), thromboxane B2 (TBX2), tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL 1), and IL-6. Inhibition of .N = O synthesis by KC. Treatment with LPS and IFN gamma also induced significant production of prostaglandin E2 (PGE2), thromboxane B2 (TBX2), tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), and IL 6. Inhibition of .N = O synthesis by the L-arginine analogue of NG-monomethyl-L arginine (NMA) resulted in a further increase of PGE2, TXB2, and IL-6 but not IL 1 and TNF-alpha production, indicating specific inhibitory effects of endogenous .N = O synthesis on the secretory activity of KCs. PGE2 production was most sensitive to the suppressive effect of .N = O and increased 24 h after stimulation with LPS and IFN-gamma from 16.3 +/- 4.9 ng/10(6) KCs without NMA to 94.3 +/- 17.9 ng/10(6) KCs with NMA. This effect of NMA was reversed by a 10-fold increase of the L-arginine concentration. No recovery of PGE2 production was seen when .N = O synthesis was blocked after 24 h. NMA treatment increased cyclooxygenase activity more than threefold, suggesting that .N = O inhibits PGE2 and TXB2 production through diminished PGH2 availability. .N = O synthesis did not significantly affect total protein synthesis or viability of the KCs. These results show that .N = O influences the production of specific inflammatory mediators by KCs. PMID- 8445329 TI - Isolation of a human endothelial cell C1q receptor (C1qR). AB - C1q binding to endothelial cells has been described previously, but the putative cell surface receptor(s) has not been identified. In the present study, modifications of a reported purification of lymphocyte C1q receptor (C1qR) were used to isolate C1q binding sites from human umbilical vein endothelial cells. Cells were harvested, without protease treatment, at passage 10-17 and lysed with 1% Triton X-100. The lysate was fractionated on Fast-performance liquid chromatography (FPLC) Mono-Q using a linear NaCl gradient, followed by high performance liquid chromatography (HPLC) ion exchange (TSKgel DEAE-NPR). A major protein was eluted that had the same mobility on sodium dodecyl sulfate polyacrylamide gels and the same NH2-terminal sequence as lymphocyte C1qR. This protein was expressed on the surface, as judged by surface radioiodination, bound to C1q-coated surfaces, and was recognized by polyclonal antilymphocyte C1qR antibodies. Thus, endothelial cells express a C1q receptor that appears identical to lymphocyte C1qR. The data further support the hypothesis that cell surface C1qRs identified on a variety of somatic and cultured cells are either identical or constitute a family of closely related molecules. PMID- 8445330 TI - Hematopoietic recovery in repeatedly irradiated mice can be enhanced by a repeatedly administered combination of diclofenac and glucan. AB - A combination of diclofenac and glucan administered repeatedly in a protective regimen in the course of repeated gamma irradiation of mice (6 x 2 Gy during 3 weeks) enhanced granulopoiesis and other indices of hematopoietic recovery investigated from 3 to 7 days after the last radiation exposure. Repeated administration of diclofenac or glucan alone or treatment of the mice with the diclofenac-glucan combination given once before the first or the last radiation exposure did not induce such effects. The protective effect of the repeatedly administered combination of the drugs was realized despite the fact that the response of the serum colony-stimulating activity to the repeated combined drug administration was decreased at the end of the treatment regimen compared to that of mice given this drug combination only once. The combined treatment is supposed to act via increased proliferation of the hematopoietic stem or progenitor cells. Additivity or even synergism of the hematostimulatory action of glucan and of the strengthening of positive control of cell proliferation achieved by removing negatively acting prostaglandins (diclofenac action) may account for the radioprotective effects observed. PMID- 8445331 TI - MRP-8 and MRP-14, two abundant Ca(2+)-binding proteins of neutrophils and monocytes. AB - Two calcium-binding proteins, named migration inhibitory factor-related proteins 8 (MRP-8) and MRP-14, are primarily expressed by circulating human neutrophils and monocytes. Evidence accumulating from the investigations of several independent groups is now leading to an improved understanding of the biology of these proteins. Both MRP-8 and MRP-14 display features characteristic of members of the S100 family of calcium-binding proteins. Some of these features predict functions for MRP-8 and MRP-14 but to date an exact and well-defined function remains elusive. Here we review the available information and highlight evidence that suggests the function of MRP-8 and MRP-14 may be associated with both monocyte and neutrophil activation and the accumulation of these cells in inflammatory sites. PMID- 8445332 TI - Optimization of peroxide production by resident macrophages. AB - Previous reports indicated that resident macrophages produced low or nondetectable quantities of H2O2 (1-10 nmol H2O2/mg resident macrophage protein) when measured by the phenol red assay described by Pick and Mizel [5]. However, modifications of the assay that included addition of calcium to assay solutions, alterations in cell-harvesting methods, increasing the concentration of cells analyzed, incubating the cells in ambient air, and enhancing the interactions between macrophages and particulate stimulants by centrifugation resulted in increased production of peroxide. Each variable was instrumental in improving the assay conditions and the combination of changes dramatically increased the amount of peroxide (30-60 nmol H2O2/mg resident macrophage protein) obtained from murine resident macrophages, making it possible to better assess the role of these cells in microbicidal killing. PMID- 8445333 TI - Effect of butter, mono- and polyunsaturated fatty acid-enriched butter, trans fatty acid margarine, and zero trans fatty acid margarine on serum lipids and lipoproteins in healthy men. AB - The effect of diets containing 50% of fat calories from butter, butter enriched with mono- and polyunsaturated fatty acids, and margarines with and without trans fatty acids on the serum lipids of 38 healthy men in a free-living condition have been determined. Serum lipid responses to the high level of individual dietary fats were unexpectedly small. The butter diet produced a small, but significant rise (5%) in the total serum cholesterol and low density lipoprotein (LDL) cholesterol, relative to all other diets. Enrichment of butter with either olive oil (50/50) or sunflower oil (50/50) failed to reduce serum lipid levels below habitual diet values. Hard margarine, containing 29% trans fatty acids, caused a decrease in apolipoprotein A-I and B levels, but did not change total serum cholesterol or LDL-cholesterol levels, relative to habitual diet values. A soft margarine, high in linoleate, with no trans fatty acids reduced total cholesterol, LDL-cholesterol, and apolipoprotein B significantly, relative to all diets. Soft margarine high density lipoprotein (HDL)-cholesterol levels remained unchanged, but apolipoprotein A-I values were decreased relative to habitual and butter diets. The quantities of saturated fatty acids and the sum of monounsaturated and polyunsaturated fatty acids consumed on the hard and soft margarines were equal; therefore, the different response of serum cholesterol and LDL-cholesterol between these two diets is attributable to the trans fatty acids in the hard margarine. The data indicate that trans fatty acids are not metabolically equivalent to the natural cis isomers and that they affect the serum lipid profile adversely. PMID- 8445334 TI - Phosphatidylinositol turnover during stimulation of plasminogen activator inhibitor-1 secretion induced by oxidized low density lipoproteins in human endothelial cells. AB - In a previous study (Latron et al. 1991. Arterioscler. Thromb. 11: 1821-1829) we have shown that oxidized low density lipoproteins (ox-LDL) stimulated the synthesis and secretion of plasminogen activator inhibitor-1 (PAI-1) by human umbilical vein endothelial cells (HUVEC) in culture. The present study is intended to give insight into the intracellular process responsible for this stimulation. The HUVEC lipids were labeled for 16 h with [3H]arachidonate and incubated either with native LDL (n-LDL) or ox-LDL for various times (15, 30, 60 min). Compared with unstimulated cells (no LDL added), ox-LDL induced a significant increase in the intracellular level of unesterified [3H]arachidonate, concomitantly with a significant decrease of the phosphatidylinositol fraction. The most marked effect was observed at 30 min and was significantly much less with n-LDL. Phospholipase inhibitors (4-bromophenacylbromide and mepacrine) added to the culture medium completely prevented the ox-LDL-induced stimulation of phosphatidylinositol degradation, [3H]arachidonate release, and PAI-1 secretion. HUVEC possess both phospholipase C and A activities and a high lysophospholipase activity, the phospholipase A pathway being in vitro more sensitive to inhibition by 4-bromophenacylbromide than the phospholipase C pathway. These results suggest that the stimulation of PAI-1 secretion by ox-LDL is mediated by the hydrolysis of membrane phosphatidylinositol through the activation of phospholipase A. PMID- 8445335 TI - Apolipoprotein A-I Milano: sex-related differences in the concentration and composition of apoA-I- and apoB-containing lipoprotein particles. AB - The presence of apolipoprotein (apo) A-IMilano (A-IM) mutant of apoA-I has a marked effect on plasma lipoproteins of A-IM carriers including variable hypertriglyceridemia, increased levels of very low density lipoproteins (VLDL), slightly elevated levels of triglyceride-enriched low density lipoproteins (LDL) and greatly reduced levels of high density lipoproteins (HDL). To gain further insight into this dyslipoproteinemic syndrome characterized clinically by the absence of coronary artery disease, we have determined the concentration and composition of apoA- and apoB-containing lipoprotein families in four male and four female carriers and corresponding normal controls. Results have shown that A IM carriers have significantly reduced levels of lipoprotein (LP) A-I (45%), LP-A I:A-II (60%), and LP-A-II (70%) and significantly increased levels of cholesterol rich LP-B (67%) and triglyceride-rich LP-B:C, LP-B:C:E, and LP-A-II:B:C:D:E (65%) particles compared to controls. However, there were significant sex-related differences in the levels of apoA-and apoB-containing lipoproteins. Female carriers had significantly higher concentrations of LP-A-I (39 +/- 10 vs. 12 +/- 6 mg/dl) and LP-A-I:A-II (48 +/- 11 vs. 30 +/- 6 mg/dl) than male carriers. Furthermore, female carriers had higher levels of LP-B:C (23 +/- 18 vs. 6 +/- 5 mg/dl) and LP-A-II:B:C:D:E (13 +/- 6 vs. 2.3 +/- 0.8 mg/dl) but lower concentrations of LP-B (103 +/- 52 vs. 152 +/- 54 mg/dl) and LP-B:C:E (5 +/- 2.5 vs. 13 +/- 8 mg/dl) than male carriers. In general, the levels of LP-A-I and LP-A I:A-II particles correlated positively with the levels of all three types of triglyceride-rich lipoproteins (LP-Bc) and negatively with the levels of LP-B particles. A comparative study of lipoprotein families in several dyslipoproteinemic states characterized by low levels of HDL has indicated that the characteristic lipoprotein particle profile of A-IM carriers results most probably from the selective effect of apoA-IM mutant rather than a general reduction in HDL levels. It appears that increased levels of LP-A-II:B:C:D:E particles, an inefficient substrate for lipoprotein lipase, and structurally defective LP-A-I:A-II particles, the normal acceptors of minor apolipoproteins released during lipolysis of triglyceride-rich lipoproteins, may be the main contributing factors to moderate hypertriglyceridemia characteristic of A-IM carriers. PMID- 8445336 TI - Metabolism of molecular species of phosphatidylethanolamine and phosphatidylcholine in rat hepatocytes during prolonged inhibition of phosphatidylethanolamine N-methyltransferase. AB - The metabolism of the molecular species of phosphatidylethanolamine (PE) and phosphatidylcholine (PC) derived from [3H]ethanolamine has been studied in rat hepatocytes during prolonged inhibition of phosphatidylethanolamine-N methyltransferase (PEMT) with 3-deazaadenosine (DZA). After an initial pulse of radioactivity for 1 h and a chase for up to 24 h in the presence or absence of DZA, the cells were harvested and the incorporation of label into the various molecular species of PE and PC was determined. Prolonged inhibition of PEMT did not affect the mol% distribution of either PE or PC molecular species. Thus, PE methylation is not required for the maintenance of cellular PE and PC molecular species composition. While the overall catabolism of PE was not affected by DZA treatment, inhibition of PEMT resulted in the selective degradation of 16:0-22:6 PE. The major catabolic products of PE in the hepatocytes and the medium were glycerophosphoethanolamine and ethanolamine-phosphate. PC, derived from PE, was remodeled at both the sn-1 and sn-2 positions and this process was not affected by the inhibition of PEMT. The major species being remodeled was 16:0-22:6-PC. The rapid turnover of 16:0-22:6-PE and PC species compared to other PE and PC species may be due to the presence of a 16:0-22:6 selective phospholipase. PMID- 8445337 TI - Docosahexaenoic acid shows no triglyceride-lowering effects but increases the peroxisomal fatty acid oxidation in liver of rats. AB - The effect of docosahexaenoic acid (DHA) on mitochondrial and peroxisomal fatty acid oxidation and on key enzymes in triglyceride metabolism was investigated in the liver of rats fed a standard diet, a cholesterol diet, and a pelleted chow diet. Unexpectedly, in all three rat models repeated administration of highly purified DHA (92% pure) at different doses and times, at a dose of 1000 mg/day per kg body weight, resulted in no significant decrease of hepatic and plasma concentration of triglycerides. The serum concentrations of cholesterol and phospholipids showed an increase in a time-dependent manner in rats fed the pelleted chow diet. The hepatic concentration of cholesterol was increased in rats fed the cholesterol diet and pelleted chow diet after administration of DHA compared to palmitic acid. In all rat models, treatment with DHA tended to increase the peroxisomal beta-oxidation. This was accompanied with a significant increase (1.5-fold) of fatty acyl-CoA oxidase activity. The mitochondrial fatty acid oxidation system and carnitine palmitoyl-transferase activity, however, were almost unchanged. Moreover, palmitoyl-CoA synthetase activity was increased, whereas the palmitoyl-CoA hydrolase activity was decreased. Neither microsomal phosphatidate phosphohydrolase activity nor cytosolic phosphatidate phosphohydrolase activity was affected by DHA feeding in the three rat models. Acyl-CoA:1,2-diacylglycerol acyltransferase activity was also unaffected. In contrast to docosahexanoic acid feeding, eicosapentaenoic acid (EPA) administration possessed a hypotriglyceridemic effect and resulted in an increase of mitochondrial and peroxisomal oxidation of fatty acids. Carnitine palmitoyltransferase activity was also stimulated. Phosphatidate phosphohydrolase activity was unaffected whereas diacylglycerol acyltransferase activity was increased by EPA treatment compared with palmitic acid feeding. The results indicate that docosahexaenoic acid, in contrast to eicosapentaenoic acid, does not inhibit the synthesis and secretion of triglycerides in the liver. In addition, the results emphasize the importance that stimulation of peroxisomal beta-oxidation by these n-3 fatty acids is not sufficient to decrease the serum levels of triglycerides. In addition, increased mitochondrial beta-oxidation of fatty acids and thereby decreased availability of nonesterified fatty acids may be a mechanism by which EPA inhibits triglyceride, and subsequently very low density lipoprotein-triglyceride, production. Whether DHA and EPA possess different metabolic properties should be considered. PMID- 8445338 TI - Endotoxin-induced hypertriglyceridemia is mediated by suppression of lipoprotein lipase at a post-transcriptional level. AB - Previous studies have demonstrated that endotoxin/lipopolysaccharide treatment causes a decrease in adipose tissue and heart lipoprotein lipase (LPL) activities in rats, producing hypertriglyceridemia in these animals. To examine the mechanisms for this effect of endotoxin, we studied the effects of endotoxin administration on LPL mRNA, and LPL synthetic rates and activity in rat adipose tissue and heart. Endotoxin treatment (i.p., 3 mg/100 g body weight or higher doses) produced a pronounced increase in serum triglycerides associated with a 65% decrease in adipose tissue and heart LPL activities within 7 h. Fast protein liquid chromatography (FPLC), used to separate lipoproteins in rat serum, showed that the increase in triglyceride was all in the very low density lipoprotein fraction which was accompanied by a concomitant decrease in high density lipoprotein. In contrast, there was no change in adipose tissue or heart LPL mRNA up to 24 h after treatment and no change in adipose tissue LPL synthetic rate, as measured by L-[35S]methionine incorporation and immunoprecipitation. Plasma insulin levels remained unchanged. The results indicate that endotoxin-induced hypertriglyceridemia in rats can be attributed to an impaired triglyceride clearance associated with a decrease of LPL activity mediated at a post transcriptional level. PMID- 8445339 TI - Metabolism of apoB-100-containing lipoproteins in familial hyperchylomicronemia. AB - The metabolism of apolipoprotein B-100 was studied in three patients with familial hyperchylomicronemia (type I hyperlipoproteinemia) using a very low density lipoprotein (VLDL) dual-tracer technique. Radioiodinated VLDL1 (Sf 60 400) and VLDL2 (Sf 20-60) were injected and their catabolism and rate of the transfer of apoB into VLDL2, intermediate density lipoprotein (IDL) (Sf 12-20), and low density lipoprotein (LDL) (Sf 0-12) were compared in patients and in five normolipidemic controls. The rates of delipidation of large triglyceride-rich VLDL1 to VLDL2 (0.26-0.54 pools/day vs. 2.5-5.2 pools/day in controls) and VLDL1 direct catabolism (0.33-0.92 pools/day vs. 4.2-14.7 pools/day in controls) were found to be significantly reduced in type I patients resulting in a tenfold increase of VLDL1 pool size. ApoB synthesis into this density interval was, however, normal as was that into smaller VLDL2. the circulating apoB mass in VLDL2 was not increased. In fact, apart from a modest decrease in the rate of VLDL2 delipidation to IDL and LDL, the behavior of apoB in this density interval was similar in hyperchylomicronemic and normal subjects. Likewise, the transfer of apoB through the IDL and LDL density ranges was not significantly different from normal. Pool sizes of these fractions, however, were reduced, the latter significantly (354-491 mg vs. 1,160-2,505 mg in controls) due to increased direct catabolism in hyperchylomicronemic patients. The results of this study indicate that lipoprotein lipase deficiency primarily affects VLDL1 metabolism, both its delipidation and direct removal from plasma. Lipolysis further down the delipidation cascade is not dependent on this enzyme. Hypercatabolism rather than a failure of synthesis of IDL and LDL was responsible for the decreased pools for both lipoproteins. PMID- 8445340 TI - Lipoprotein lipase regulation in the cyclophosphamide-treated rabbit: dependence on nutritional status. AB - Cyclophosphamide injection into the fasted rabbit induces a hypertriglyceridemia (4.6 mM vs. 0.8 mM in controls) and a defect of lipoprotein lipase (LPL), as measured in post-heparin plasma (PHP). In contrast, administration of the drug into fed animals tends to increase PHP-LPL. The effects of cyclophosphamide on LPL activity and synthesis, depending on the nutritional state, were thus studied in two sites: periepididymal adipose tissue and heart. In adipose tissue, fasting decreased LPL activity to 45.2 mIU/g (P < 0.001) compared to 667.9 mIU/g in fed animals. PHP-LPL activity was also decreased by 45% upon starvation. These modulations appeared to be related to plasma insulin levels. The relative rate of synthesis of fat tissue LPL was decreased from 0.32% total protein synthesis in fed animals to 0.10% in fasted rabbits, concordant with a reduction in the expression of LPL specific mRNA. Cyclophosphamide administration to the fed rabbit led to decreases of LPL activity and synthesis in the adipose tissue, similar to those observed upon starvation. However, when injected into fasted animals, the drug did not further depress fat tissue LPL. Fasting did not change heart LPL activity (288.3 mIU/g vs. 239.3 in fed animals) nor its relative rate of synthesis (0.21% of total protein synthesis). However, cyclophosphamide induced opposite effects, depending on the nutritional state: after injection into fed animals, heart LPL activity increased up to 477.2 mIU/g (P < 0.01) with a concomitant increase in the LPL synthesis rate. Conversely, drug administration into fasted rabbits led to a decrease of heart LPL activity to 133.9 mIU/g. Similar qualitative variations were recorded in postheparin plasma. Hence, although insensitive to nutritional modulations, heart LPL responded differently to cyclophosphamide, depending on the nutritional state. In spite of those different modulations of heart and adipose tissue LPL, the enzyme isolated from these two sources displayed similar molecular mass, immunoreactivity, and catalytic properties. The effects of cyclophosphamide injection on very low density lipoprotein (VLDL)-triacylglycerol (TG) synthesis were also investigated, as a possible determinant of hypertriglyceridemia. The drug stimulated TG synthesis in both nutritional states, and maximally by 45% in fed animals. Hence, a defect of heart and postheparin plasma LPL appears as a major determinant of hypertriglyceridemia in cyclophosphamide-treated fasted rabbits.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8445341 TI - Transformation of HepG2 nascent lipoproteins by LCAT: modulation by HepG2 d > 1.235 g/ml fraction. AB - We have previously shown that lecithin:cholesterol acyltransferase (LCAT) can transform ultracentrifugally isolated HepG2 lipoproteins (d < 1.235 g/ml) into particles that differ substantially from their nascent precursors. Transformed high density lipoprotein (HDL) subpopulations, as judged by nondenaturing gradient gel electrophoresis (GGE), resemble plasma HDL, i.e., HDL2a- and HDL3a sized particles predominate. In HepG2 conditioned medium (CM), 60-70% of apoA-I is in the d > 1.235 g/ml fraction (lipid-poor apoA-I); hence we investigated whether inclusion of d > 1.235 g/ml fraction in LCAT incubations altered HDL subpopulations. After 18 h incubation of CM (containing lipoproteins and d > 1.235 g/ml fraction) with purified LCAT, the major transformation product on GGE was a large 9.7-nm particle (HDL2b pattern); a minor component appeared at 7.4 nm (HDL3c). Differences in particle size distribution between CM and isolated lipoprotein incubations were not the result of differences in LCAT activity; mass ratios of unesterified cholesterol:cholesteryl ester and phospholipid:cholesteryl ester were similar. Removal of apoA-I from the d > 1.235 g/ml fraction by immunoaffinity chromatography prior to incubation with the d < 1.235 g/ml fraction produced the same products (i.e., HDL2b pattern) as incubations performed with the unaltered d > 1.235 g/ml fraction; therefore, lipid-poor apoA I does not influence nascent HDL transformation. Cholesteryl ester was transferred from HepG2 HDL to LDL in CM incubations; however, cholesteryl ester transfer protein was not immunochemically identified. Removal of HepG2 LDL from CM prior to incubation with LCAT still resulted in the HDL2b pattern. We conclude that HepG2 cells secrete a factor(s) that modifies nascent HDL transformation products into a predominantly HDL2b subpopulation. PMID- 8445342 TI - Two different allelic mutations in the lecithin:cholesterol acyltransferase (LCAT) gene resulting in classic LCAT deficiency: LCAT (tyr83-->stop) and LCAT (tyr156-->asn). AB - The molecular defects in the lecithin:cholesterol acyltransferase (LCAT) gene have been identified in a 52-year-old patient with classic LCAT deficiency, presenting with corneal clouding and proteinuria. Plasma total cholesterol was normal, triglycerides were elevated, whereas high density lipoprotein (HDL) cholesterol (8 mg/dl) and plasma cholesteryl esters (6% of total cholesterol) were markedly reduced. Plasma cholesterol esterification rate (pCER) was zero, alpha-LCAT activity, assayed using an HDL-like proteoliposome substrate was reduced to 1.6% of control, and LCAT mass was 3.7% of normal plasma levels. DNA sequence analysis of the proband's LCAT gene identified a C to A substitution, converting tyr83 to a stop codon, and a T to A transition, replacing tyr156 by asn. Restriction analysis of PCR-amplified DNA from the proband, a control and his four children using the enzymes Acc I and Rsa I established that the patient is a compound heterozygote for both mutations. The two children, heterozygous for the stop codon defect, were phenotypically indistinguishable from the two with the tyr156 defect. In vitro expression of LCAT (tyr156-->asn) in human embryonic kidney-293 cells established the functional significance of this mutation. The secreted translation product had only 6% of control mass and no detectable CER; however, the residual LCAT mass of the in vitro expressed LCAT (tyr156-->asn) demonstrated a specific alpha-LCAT activity of 30% of control, suggesting that this amino acid substitution results in a mutant enzyme that retains some enzymic activity, but may be rapidly catabolized. In summary, we have identified two unique defects in the LCAT gene that lead to the expression of classic LCAT deficiency in this kindred. PMID- 8445343 TI - Effects of ketoconazole on cholesterol precursors and low density lipoprotein kinetics in hypercholesterolemia. AB - Ketoconazole, an inhibitor of cholesterol synthesis at 14 alpha-demethylation of lanosterol, effectively reduces serum total and low density lipoprotein (LDL) cholesterol levels. We studied the effects of ketoconazole (400 mg/day for 5 weeks) on serum lipids, free and esterified noncholesterol sterols, and kinetics of LDL apolipoprotein B (apoB) in seven patients with heterozygous familial hypercholesterolemia (FH) and in three patients with primary hypercholesterolemia (nonFH). The total, intermediate density, and LDL cholesterol levels were significantly reduced by 24, 27, and 29%, respectively, and LDL apoB by 23%. Serum total and lipoprotein triglycerides were unchanged. The LDL cholesterol/apoB ratio decreased significantly. Serum ratios of lanosterols to cholesterol were increased over 50 times, almost the same in all lipoproteins and mainly as the unesterified form; free delta 8-precursor sterols, 2-5 times; cholestanol, slightly; while ratios of lanosterol of desmosterol, lathosterol, and plant sterols were virtually unchanged. Inconsistent esterification of methyl sterols might indicate unaltered acyl CoA:cholesterol acyltransferase activity. LDL apoB transport was decreased in all nonFH subjects but inconsistently in FH. The fractional catabolism rate (FCR) for LDL apoB was increased significantly in FH by 13% and inconsistently by 4% in nonFH. In a subgroup of three FH patients, more dense LDL (d 1.037-1.055 g/ml) was transported and catabolized faster on than off ketoconazole so that the serum level of this more dense LDL subfraction was unchanged, the decrease of LDL being due to a reduction of the less dense LDL subfraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8445344 TI - Assessment of 5-lipoxygenase involvement in human monocyte-mediated LDL oxidation. AB - Lipoxygenase (LO) activity has been implicated in the process by which activated human monocytes oxidize normal human low density lipoprotein (LDL) and render it toxic to target cells. Here we examined the role of 5-LO in activated monocyte mediated LDL modification. Five putative inhibitors of 5-LO (A63162, CGS8515, PF5901, RG6866, and MK886) were used to determine if they prevented activated monocytes from oxidizing LDL. Only RG6866, A63162, and CGS8515 inhibited monocyte mediated LDL oxidation. Nonspecific effects of these drugs on LDL oxidation by activated monocytes were examined. RG6866 and A63162 were both found to be general antioxidants at their effective concentrations. CGS8515 was toxic at its effective concentration. A63162, CGS8515, and RG6866 also inhibited 15-LO activity in vitro. MK886 and PF5901 did not exhibit the nonspecific effects above and did not inhibit monocyte-mediated LDL oxidation, whereas both MK886 and PF5901 inhibited production of 5-LO metabolites by activated monocytes at concentrations that had no effect on LDL oxidation by the activated monocytes. Since neither of these agents inhibited LDL oxidation, we conclude that 5-LO is not involved in human monocyte oxidation of LDL. The possibility that a cellular 12- or 15-LO is involved in human monocyte-mediated LDL oxidation remains to be evaluated. PMID- 8445345 TI - Recombinant lecithin:cholesterol acyltransferase containing a Thr123-->Ile mutation esterifies cholesterol in low density lipoprotein but not in high density lipoprotein. AB - Fish-eye disease is a rare genetic disorder of high density lipoprotein (HDL) metabolism that is characterized biochemically by a partial deficiency of the enzyme lecithin:cholesterol acyltransferase (LCAT). One of the mutations that is causative for fish-eye disease occurs at codon 123 of the LCAT gene. This mutation results in the exchange of a threonine residue for an isoleucine in the LCAT protein (Thr123-->Ile). In order to understand the functional significance of this exchange, we have used site-directed mutagenesis to reconstruct this mutation in an LCAT cDNA followed by expression of the mutant LCAT in COS-1 cells. The fish-eye disease mutation resulted in a 50% decrease in LCAT mass in the culture medium compared to wild type enzyme. The secreted mutant protein was incapable of esterifying cholesterol in HDL and HDL analogues. However, this protein retained the ability to esterify cholesterol in plasma and low density lipoprotein. These results support the hypothesis that this mutation is responsible for biochemical abnormalities of LCAT observed in fish-eye disease and the mutant LCAT protein has lost the potential to esterify cholesterol in the HDL pool but retains the ability to esterify cholesterol from other lipoproteins. PMID- 8445346 TI - Infusion of atherogenic lipoprotein particles increases hepatic lipase activity in the rabbit. AB - Hepatic lipase plays a key role in the turnover of potentially atherogenic lipoprotein remnants and in determining the relative distribution of high density lipoprotein (HDL) particle size subclasses. Rabbits fed a cholesterol-enriched diet have been found to accumulate potentially atherogenic chylomicron remnants and beta-very low density lipoprotein (beta-VLDL) and show a rapid increase in liver and postheparin plasma hepatic lipase activity. To determine whether the particles that accumulate during cholesterol feeding are a stimulus for this increase in hepatic lipase activity, we infused normal chow-fed rabbits with a chylomicron remnant plus beta-VLDL-enriched plasma fraction isolated from rabbits fed 0.5% cholesterol-supplemented chow. The infusion of this plasma fraction for 4 h increased hepatic lipase activity up to 2.9-fold over control rabbits and resulted in a loss of larger sized HDL particles consistent with the action of hepatic lipase. The increase in activity was significantly correlated with the concentration of infusate phospholipid, unesterified cholesterol, and esterified cholesterol, but not with the infusate triglyceride concentration. The change in the plasma cholesterol concentration of recipient rabbits, which reflects the degree of lipoprotein accumulation in these rabbits, was also significantly correlated with the change in hepatic lipase activity. However, a chylomicron remnant and beta-VLDL-depleted fraction of plasma from cholesterol-fed rabbits did not increase hepatic lipase activity. Furthermore, triglyceride presented as an artificial lipid emulsion (Intralipid) was not able to stimulate hepatic lipase activity, although triglyceride is a substrate for hepatic lipase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8445347 TI - Identification of bile acid coenzyme A synthetase in rat kidney. AB - Bile acid CoA synthetase has been discovered in rat kidney. Incubation of kidney microsomes with [14C]chenodeoxycholic acid and CoA produced a single peak with the high performance liquid chromatography (HPLC) retention time of CDC-CoA. This peak, when incubated with purified bile acid CoA: amino acid N-acyltransferase (BAT) from human liver and either taurine or glycine, led to the formation of CDC taurine or CDC-glycine, respectively. Kinetic analysis revealed apparent Kms for CDC and CoA of 2.5 microM and 2.6 microM, respectively. This activity appeared specific for bile acids as it was not inhibited by benzoic acid or salicylic acid, known substrates for other rat kidney CoA synthetases. This demonstrates that the kidney has the potential for bile acid metabolism and may have a role in bile acid physiology. PMID- 8445348 TI - A host-parasite model yielding heterogeneous parasite loads. AB - Many models of parasitic infections lead to an approximately Poisson distribution of parasites among hosts, in stark contrast to the highly over-dispersed distributions that are usually encountered in practice. In this paper, a model is analyzed which, while assuming all individuals to be alike, can still lead to a very heterogeneous distribution of parasites among the host population. The model can be viewed as a very simple mean field interacting particle system, with the particles corresponding to the individual hosts, which behaves like an associated deterministic system when the number of hosts is large. The deterministic system describes the evolution over time of the proportions of the population with different parasite loads and its equilibria are interpreted as typical distributions of parasites among hosts. Despite its simplicity, the model is complicated enough mathematically to leave a number of open problems. PMID- 8445349 TI - On the probability of loss of new mutations in the presence of linkage disequilibrium. AB - A new selectively neutral mutation occurs in a multilocus genetic background that has achieved a stable equilibrium at which there is a linkage disequilibrium. Perturbation techniques are applied to an extension of the branching process formulation of Fisher in order to address the question of extinction probabilities. We show that under appropriate conditions the probability of extinction of the new mutant is increased by the existence of linkage disequilibrium in the genetic background. PMID- 8445350 TI - Stochastic dynamical aspects of neuronal activity. AB - A stochastic model of neuronal activity is proposed. Some stochastic differential equations based on jump processes are used to investigate the behavior of the membrane potential at a time scale small with respect to the neuronal states time evolution. A model for learning, implying short memory effects, is described. PMID- 8445351 TI - Normal pressure hydrocephalus. AB - Normal pressure hydrocephalus is a clinical syndrome associated with dementia, urinary incontinence, gait apraxia and computed tomography or magnetic resonance imaging evidence of communicating hydrocephalus. In the elderly patient, these symptoms may be overlooked or discounted if the clinician is not well versed in this condition. Normal pressure hydrocephalus has classically been described as an idiopathic disorder. Recent studies indicate that this syndrome may be associated with deep white matter infarction. This article discusses the case of a patient who suffered from this condition. Clinical information is presented. PMID- 8445352 TI - The use of transverse friction massage in the management of chronic bursitis of the hip or shoulder. AB - This article discusses two cases of chronic bursitis of the hip and shoulder treated by transverse friction massage. While clinical evidence has substantiated the benefits of friction massage on chronic tendinitis, previous literature has discouraged the use of friction massage in chronic bursitis. A functional examination and attention to associated biomechanical faults are also necessary for a complete noninvasive manual resolution of the problem. PMID- 8445353 TI - Basilar artery migraine or cerebral vascular accident? AB - There are no reports of misdiagnosis of postmanipulative stroke in the literature. This report discusses a case of basilar artery migraine that was misdiagnosed as such. The main diagnostic features of this rare condition are highlighted, as are the relevant differential diagnoses. PMID- 8445354 TI - Five steps to your own technique: the Nelson method. PMID- 8445355 TI - Rotator cuff disease: current trends in orthopedic management. PMID- 8445356 TI - A comparison of outcome measures for use with back pain patients: results of a feasibility study. AB - OBJECTIVE: To compare the reliability, validity and change in patient clinical status over time with treatment for six potential outcome questionnaires in a defined population of patients. SETTING: Physician based, multidoctor teaching practice. PATIENTS: Three hundred thirty-five consecutive patients presenting with new complaints were solicited. One hundred eighty-six agreed to participate. INTERVENTIONS: The six questionnaires being studied were administered to each of the participants on three separate occasions. They were: a) prior to clinical evaluation for their chief complaint, b) immediately after clinical evaluation and before treatment and c) 6 wk later. MEASUREMENTS: Each instrument was scored following the prescribed methods of interpretation from the original literature describing it. Results were submitted for analysis by Pearson correlation and two way analysis of variance as appropriate. MAIN RESULTS: Differences were found in the mean value of the modified Zung with respect to both gender and time. An unexpected drop in patients' somatic perceptions in association with the process of clinical evaluation was found for the Modified Somatic Pain Questionnaire. Overall, the Oswestry and Visual Analogue Pain Scale were the most reliable and responsive to clinical change for musculoskeletal disorders. CONCLUSIONS: This investigation demonstrated substantial differences in the validity and reliability of commonly referenced self-administered instruments for quantifying patient perceptions of pain and disability. The Oswestry and Visual Analogue Pain Scale were both more reliable and valid than other instruments. PMID- 8445357 TI - Biomechanical analysis of an induced joint dysfunction (subluxation-mimic) in the thoracic spine of rabbits. AB - OBJECTIVE: The purpose of the present experiment was to evaluate functional biomechanics of the lesioned area in rabbits subjected to surgically placed vertebral lesions which may mimic a subluxation. It was hypothesized that wedging a bar between three adjacent vertebrae would lead to visual and palpatory alterations and also to a decrease in range of motion (ROM) at the affected segments. DESIGN: A controlled laboratory experiment was performed to measure directly ROM and to evaluate the functional and anatomic relationships of vertebrally lesioned rabbits. SUBJECTS: Twelve healthy adult New Zealand rabbits of either sex, weighing 3-5 kg, were maintained in the PCC animal facilities under normal husbandry conditions. Six operated controls and six experimentally lesioned rabbits were available for analysis. INTERVENTIONS: Rabbits were anesthetized and a vertebral lesion surgically placed at various locations along the thoracic spine. A stainless steel bar was implanted to produce a putative partial fixation and misalignment of three adjacent segments. The middle spinous process was forced contralaterally and slightly rotated relative to the adjacent two. At intervals ranging from a few weeks to several months postsurgery, the animals were evaluated for spinal ROM and also by visual and palpatory means for spinal misalignment. MAIN OUTCOME MEASURE: X rays, using rubber foam molds to standardize positioning, were taken pre- and postsurgery to measure ROM. Statistical analysis was made to compare ROM between the lesioned and adjacent areas of experimental and control animals. RESULTS: All but one of the experimental animals, but none of the controls, showed some reduced ROM on palpation at autopsy. Radiographic measures, however, showed that the ROM in the experimental animals as a group was not significantly reduced compared to control values, nor was there a significant ROM decrease compared to nonlesioned motor units within the experimental group. In some individual animals, however, there was a significant decrease in spinal ROM. CONCLUSIONS: This study failed to demonstrate any effect of the vertebral lesion on spinal ROM as measured radiographically, although by palpation the lesioned area did appear to be partially fixated in most animals. This surprising result may perhaps be explained by the large variability in measurements, the small number of subjects used or by inadequacies of X-ray positioning. Further work on biomechanical effects of vertebral lesions is clearly required. PMID- 8445358 TI - Treatment and biomechanical assessment of patients with chronic sacroiliac joint syndrome. AB - OBJECTIVE: To evaluate diagnostic and biomechanical correlates and treatment outcomes of manipulative/adjustive care in patients highly selected for sacroiliac joint syndrome (SIJS). DESIGN: Descriptive case series, 1 wk baseline, 1 yr follow-up. SETTING: Private chiropractic practice. PATIENTS: Ten out of 153 consecutive new patients (4 male and 6 female) with "primary," chronic, uncomplicated SIJS were selected over an 11-mo period on the basis of painful SIJ and provocation tests. MAIN OUTCOME MEASURES: Back pain (visual analogue scale), Oswestry disability index, lumbar provocation tests and biomechanical measures of gait and postural sway. INTERVENTION: Six-wk regimen of mechanical force, manually assisted, short lever adjustments (MFMA) with an Activator instrument. RESULTS: Pain decreased significantly from a mean baseline value of 25 to 12 (t = 2.28; p < .05). Likewise, the average disability scores diminished from 28 to 13% (t = 2.3; p < .05), and a reduction in the number of positive provocation tests was noted (Fisher Exact Probability range Z = 0.025-0.045). Gait and sway parameters were indistinguishable from normals, before or after treatment. Response to the 1-yr follow-up questionnaire (6/10) revealed stability of symptoms at a low level. CONCLUSIONS: While the majority of subjects recorded some degree of positive outcome, we conclude that: a) discrete SIJS remains difficult to diagnose, but may be possible by judicious choice of screening tests; b) MFMA may benefit some patients with chronic SIJ pain; and c) gait and sway measurement yielded no correlation with clinical conditions. PMID- 8445359 TI - Effect of cervical spinal adjustments on lumbar paraspinal muscle tone: evidence for facilitation of intersegmental tonic neck reflexes. AB - OBJECTIVES: To determine whether spinal adjustments, delivered to the upper vs. lower cervical spine, might result in tonic neck reflex-induced alterations in the activity of the lumbar paraspinal musculature. DESIGN: Randomized, double blind, before/after treatment comparisons. SETTING: Cervical Ergonomics Laboratory, Palmer College of Chiropractic-West, Sunnyvale, CA. SUBJECTS: Healthy, nonsymptomatic chiropractic college students, about evenly divided with respect to gender and ranging from 23-38 yr of age. INTERVENTION: Modified "diversified" spinal adjustments, delivered bilaterally to either the upper (C2) or lower (C7) cervical region. MAIN OUTCOME MEASURE: Tissue compliance measures using a tissue compliance meter, obtained from each subject at sites 2 cm on either side of the spinous processes of L1, L2, L3, L4 and L5 both prior to and within 15 min following treatments. RESULTS: Upper cervical adjustments produced changes in lumbar tissue compliance which were only slight (p < .05) and not significantly different from that which occurred following upper cervical sham manipulation (p > .1). However, lower cervical adjustments induced increases in tissue compliance (decreases in tone) which were highly significant (p < .001) and relatively robust compared to those found following upper cervical adjustments (p < .01). Furthermore, the greatest effects were observed on either side of the L4 and L5 spinous processes, suggesting influences on the gluteal musculature in particular. CONCLUSIONS: Results indicate that cervical spinal manipulation can have significant effects on the tone of the lumbopelvic musculature, presumably by facilitating tonic neck reflexes involving intersegmental spinal pathways. PMID- 8445360 TI - Side posture manipulation for lumbar intervertebral disk herniation. AB - OBJECTIVES: The objective of this article is to review the status of side posture manipulation for lumbar intervertebral disk herniation. DATA SOURCES, STUDY SELECTION AND DATA EXTRACTION: The data presented in this article are from our Back Pain Clinic at the Royal University Hospital and the articles cited are those which we feel are important in reviewing this subject. CONCLUSIONS: The treatment of lumbar intervertebral disk herniation by side posture manipulation is both safe and effective. Further research is required to understand more fully the effects of this treatment on the intervertebral disk. PMID- 8445361 TI - Nucleotide sequence of one component of the banana bunchy top virus genome contains a putative replicase gene. AB - One DNA component of the banana bunchy top virus (BBTV) genome was cloned and sequenced. This component is present as a circular, ssDNA in the virions and consists of 1111 nucleotides. It contains one large open reading frame (ORF) of 858 nucleotides in the virion sense; this ORF encodes a putative replicase based on the presence of a dNTP-binding motif (GGEGKT). Two smaller ORFs (249 and 366 nucleotides), in the complementary orientation, could not be assigned any obvious function. Neither of these ORFs had significant sequence homology with any known DNA plant virus gene or gene product. Computer analysis of this component predicted a strong stem-loop structure in the virion sense putative untranslated region; a nonanucleotide sequence in the loop was nearly identical to the nonanucleotide invariant loop sequence of geminiviruses and coconut foliar decay virus. There is strong evidence that the genome of BBTV consists of more than one component because no ORF was found that would encode a protein the size of the BBTV coat protein. BBTV has some characteristics in common with geminiviruses but cannot be classified as one. Rather, BBTV probably belongs to an undescribed plant virus group which could also include subterranean clover stunt virus and coconut foliar decay virus. PMID- 8445362 TI - 3'-terminal sequence of the plum pox virus PS and o6 isolates: evidence for RNA recombination within the potyvirus group. AB - The sequence of the 3'-terminal 1768 nucleotides of the PS and o6 isolates of plum pox virus (PPV) has been determined and compared with that of the equivalent regions of other PPV isolates sequenced previously. The sequenced region is part of the PPV open reading frame encoding the last 186 amino acids of the NIb protein and the coat protein (CP, 330 amino acids), followed by a non-coding region of 220 nucleotides and a poly(A) tail. PPV-PS and PPV(-)o6, just like PPV El Amar, show rather high levels of nucleotide diversity in the sequence encoding the C-terminal region of the NIb protein (19.4 to 31%) and the N terminus of CP (22.8 to 41.1%) when compared with PPV-Rankovic, PPV-D and PPV-NAT, whereas the level of diversity in the rest of the CP sequence and the 3' non-coding region is low (8 to 10.8% and 5.5 to 7.7%, respectively). However, the first 429 sequenced nucleotides of PPV(-)o6 are very similar to those of the PPV-Rankovic, PPV-D and PPV-NAT isolates, whereas the rest of the sequence clearly resembles PPV-PS. Thus, PPV(-)o6 seems to be the result of a natural recombination event between two wild strains of PPV. To our knowledge this is the first evidence of homologous RNA recombination (a process which could play an important role in the evolution of RNA viruses) within the potyvirus group. PMID- 8445363 TI - Evidence that cowpea aphid-borne mosaic and blackeye cowpea mosaic viruses are two different potyviruses. AB - The immunoreactivity of a panel of polyclonal antibodies and monoclonal antibodies (MAbs) raised against African isolates of potyviruses from cowpea and African yam bean was examined in ELISAs. A serological study including reference isolates followed by further characterization in differential hosts resulted in separation of the potyviruses into two distinct serogroups, one containing blackeye cowpea mosaic virus (BlCMV) and the other containing cowpea aphid-borne mosaic virus (CAMV). Using biotin-labelled MAbs, the BlCMV isolates were further subdivided into two serotypes and the CAMV isolates into five serotypes. Because both BlCMV and CAMV induce a very similar mosaic disease in cowpea, different ELISA procedures using mixed MAbs were evaluated and a single protocol was developed which allowed reliable diagnosis of both viruses. PMID- 8445364 TI - Multiplication of tomato spotted wilt virus in its insect vector, Frankliniella occidentalis. AB - The accumulation of two proteins, the nucleocapsid (N) protein and a non structural (NSs) protein both encoded by the S RNA of tomato spotted wilt virus (TSWV), was followed in larvae during development and in adults of Frankliniella occidentalis after ingesting the virus for short periods on infected plants. The amounts of both proteins increased, as shown by ELISA and Western blot analysis, within 2 days above the levels ingested, indicating multiplication of TSWV in these insects. Accumulation of these proteins and of virus particles was further confirmed by in situ immunolabelling of the salivary glands and other tissues of adult thrips. The accumulation of large amounts of N and NSs protein, the occurrence of several vesicles with virus particles in the salivary glands and the massive numbers of virus particles in the salivary gland ducts demonstrate that the salivary glands are a major site of TSWV replication. The occurrence of virus particles in the salivary vesicles is indicative of the involvement of the Golgi apparatus in the maturation of the virus particles and its transport to the salivary ducts. PMID- 8445365 TI - Characterization of new baculovirus genotypes arising from inoculation of Pieris brassicae with granulosis viruses. AB - Previous studies have shown that of 15 Artogeia (Pieris) rapae granulosis virus isolates (ArGV1 to ArGV15) only two, ArGV1 and ArGV2, gave a normal dose mortality response in larvae from an established colony of Pieris brassicae. We report here that at extremely high doses, approaching 10000 times the LD50 for ArGV1 and ArGV2, three other ArGV isolates caused low and irregular levels of mortality in P. brassicae. At similar doses Agrotis segetum GV caused 43% mortality in one infection, but no deaths ensued from other inoculations with this virus. Restriction endonuclease analysis of viral DNA recovered from individual larval cadavers revealed that, in most cases, progeny virus differed from the inoculum and consisted either of ArGV1 or of novel genotypes explicable as recombinants between genomes of the inoculum and of ArGV1. Field-collected P. brassicae inoculated with ArGV8 yielded a similar range of progeny genotypes. Physical maps were constructed for two such recombinants, based on comparative restriction analysis with reference to the published map of ArGV1 and to those of ArGV5 and ArGV8, which are presented. Replication of the inoculum genotype was observed in only two infections. The origin of ArGV1 DNA appearing among progeny from these infections and the relevance of our results to identifying ArGV DNA sequences that modulate pathogenicity for P. brassicae are discussed. PMID- 8445366 TI - Molecular characterization of two isolates of human T cell leukaemia virus type II from Italian drug abusers and comparison of genome structure with other isolates. AB - The human T cell leukaemia virus type II (HTLV-II), whose pathogenicity is as yet unclear, was recently found to be associated with intravenous drug abuse in North America and Europe. HTLV-II was isolated from two Italian drug abusers belonging to the same cohort and coinfected with human immunodeficiency virus type 1. Two new isolates, HTLV-II Gu and Va, were established in a culture of BJAB cells, a continuous B cell line (Epstein-Barr virus-negative), and characterized by nucleotide sequence analysis of the long terminal repeat (LTR) and portions of the gag, env and X regions. These sequences were compared to those of the HTLV-II Mo isolate reported in the literature. No major variations were observed in important regulatory elements of LTR nor in the stem-bulge-loop configuration known to be essential for binding of rex protein. The results obtained from the sequence of the 1988 nucleotides examined indicated a 1.6% variability between the Gu and Va isolates and about 6% with respect to Mo. Notable differences were found in the structure of putative open reading frames of the X region when compared to those reported for the Mo isolate. Restriction analysis of proviral DNA of two isolates and comparison with the physical map of the Mo isolate confirmed the existence of genetic heterogeneity in the HTLV-II group and demonstrated that the new isolates Gu and Va belong to the HTLV-IIb subtype. The results of this study show that the new isolates have distinct features with respect to the Mo isolate though all important regulatory elements of the LTR appear to be well conserved. PMID- 8445367 TI - Mapping cell-mediated immunodominant domains of the rubella virus structural proteins using recombinant proteins and synthetic peptides. AB - Although it is known that rubella-immune individuals have T cells that proliferate in vitro in response to rubella virus (RV), the determinants that evoke this response have not been identified. This study utilized recombinant proteins that express overlapping sequences of the RV structural open reading frame to identify domains of the structural proteins that contain cell-mediated immunodominant sequences. Lysates enriched with RV fusion proteins (RecA-RV-LacZ) were prepared from Escherichia coli transformed with plasmids which contained specific RV cDNA inserts. Approximately 62% of RV-immune individuals gave RV specific responses to one or more of the RV fusion proteins. Over 10% of immune individuals recognized the capsid sequence C1-C29. Lymphoproliferation data from studies using six overlapping synthetic peptides representing this sequence suggested that as much as 70% of the immune population may recognize this domain. An E1 sequence, E1(202)-E1(283), was recognized by 15% of the RV-immune individuals with the fusion proteins. Five synthetic peptides representing this sequence had an overall response rate of 50%. The sequence C64-C97 failed to evoke any RV-specific responses with the fusion proteins and synthetic peptides representing this sequence were used to verify that the RV fusion proteins and the criteria used to identify RV-specific responses were adequate. These peptides gave a response rate of only 6%. In general, significant responses to specific fusion proteins correlated with high responses (stimulation index > or = 4.0) to representative synthetic peptides. This study suggests that the recombinant proteins were beneficial in identifying cell-mediated immunodominant domains of the RV structural proteins which could be further characterized with synthetic peptides. PMID- 8445369 TI - The structure of the 5' terminal cap of the respiratory syncytial virus mRNA. AB - The 5' terminal cap structure of the mRNAs of human respiratory syncytial virus synthesized in vitro in the presence of S-adenosyl-L-methionine consists of a 7 methyl guanosine linked to an unmethylated guanosine through a 5'-5' pyrophosphate linkage formed by using the alpha and beta phosphates of GTP. The complete cap structure is m7G (5')ppp(5')Gp ... which is devoid of ribose 2'-O methylation. Capping, including methylation, is coupled to transcription. These results constitute the first report of a pneumoviral mRNA cap structure. PMID- 8445368 TI - Expression of the G glycoprotein gene of human respiratory syncytial virus in Salmonella typhimurium. AB - The attachment protein, G, of human respiratory syncytial virus (RSV) is an M(r) 84K to 90K species which has a high content of N-linked and O-linked carbohydrates. The unglycosylated form of this protein was expressed by inserting a full-length cDNA copy of the mRNA from the A2 strain of RSV into a prokaryotic expression vector under the control of the lambda PL promoter. Salmonella typhimurium cells transformed with the G-containing plasmid synthesized a protein of M(r) 40,000 that specifically reacted with polyclonal and two neutralizing monoclonal antibodies raised against the native RSV G glycoprotein. Recombinant G protein was purified by immunoaffinity chromatography using a neutralizing monoclonal antibody. Cotton rats immunized with the recombinant G protein produced serum antibodies to the G glycoprotein that neutralized RSV in vitro. The study demonstrates that the G protein of RSV can be expressed in bacteria and that at least one neutralizing epitope is not structurally dependent on carbohydrates. PMID- 8445370 TI - Susceptibility of human cells to Puumala virus infection. AB - Nephropathia epidemica involves several organs including kidney, lung, liver and brain. To investigate the susceptibility of putative target cells to the agent responsible, Puumala virus, we screened established human cell lines of lung (WI 38, A-427, CCD-11Lu), kidney (A-704), liver (Hep G2), pharynx (Detroit 562), submaxillary gland (A-253) and neural (SK-N-MC, SH-SY5Y) origin as well as primary human kidney glomerular cells, endothelial cells and peripheral blood monocytes/macrophages. Propagation of the Sotkamo strain of Puumala virus was also tested in the primary kidney, spleen and lung cells of bank voles (the natural host of the virus). All of the primary cells and most of the established cell lines expressed viral protein, synthesized viral RNA and secreted infectious virus, except the neural SK-N-MC and SH-SY5Y cells. None of the tested cell types except the primary bank vole kidney cells could propagate the virus as efficiently as the Vero E6 cells. The observed host cell range is wide and consistent with a multiorgan involvement of Puumala virus. No cytopathic effects were seen in any of the infected cell cultures. PMID- 8445371 TI - Molecular evidence that epizootic Venezuelan equine encephalitis (VEE) I-AB viruses are not evolutionary derivatives of enzootic VEE subtype I-E or II viruses. AB - Enzootic strains of Venezuelan equine encephalitis (VEE) virus occur in the United States (Florida), Mexico, Central America and South America. Epizootic VEE first occurred in North and Central America in a widespread outbreak between 1969 and 1972. To investigate the likelihood that this epizootic VEE virus, identified as VEE antigenic subtype I-AB, evolved from enzootic viruses extant in the region, we cloned and sequenced the 26S mRNA region of the genomes of the Florida VEE subtype II virus, strain Everglades Fe3-7c, and the Middle American subtype I E virus, strain Mena II. This region of the genome encodes the viral structural proteins. The sequences of the 26S mRNA regions of the Everglades and Mena virus genomes differed from that of the reference epizootic VEE subtype I-AB virus, Trinidad donkey strain, by 453 and 887 nucleotides and by 66 and 131 amino acids, respectively. These data confirm previous reports demonstrating significant antigenic and genetic distance between VEE I-AB virus and viruses of subtypes I-E and II. It is unlikely that the epizootic VEE I-AB virus responsible for the 1969 outbreak originated from mutation of enzootic VEE viruses in North or Middle America. PMID- 8445372 TI - Suicide as psychache. PMID- 8445373 TI - Culture, biology, and the near-death experience. A reappraisal. AB - Life review and tunnel sensation in near-death experiences appear to be culture bound phenomena, confined largely to societies where historic religions are dominant. The clinical literature postulating biological theories for life review and tunnel sensations, therefore, may have been developed somewhat prematurely. The present review argues that social and historical explanations are more persuasive in the context of the available evidence presented here. PMID- 8445374 TI - The prevalence of ataques de nervios in the Puerto Rico disaster study. The role of culture in psychiatric epidemiology. AB - This paper presents one of the few epidemiological studies of a popular category of distress, ataques de nervios (attacks of nerves), in the cross-cultural psychiatric literature. As part of a major study of the psychological consequences of the 1985 floods and mudslides which caused considerable damage and death in Puerto Rico, a question was added to the Diagnostic Interview Schedule/Disaster Supplement concerning ataques de nervios. This additional item provided the opportunity to carry out the first study of this important Puerto Rican popular category of distress using a representative, community-based sample. This paper addresses several key questions about ataques de nervios which come from previous psychiatric and anthropological literatures concerning the social correlates of who experiences an ataque de nervios and the relationship of ataques to social distress and psychiatric disorder. People who reported an ataque de nervios were more likely to be female, older, less educated, and formerly married. They were also more likely to meet criteria for anxiety and depressive disorders than those who had not experienced an ataque. The picture that emerges from our analyses is that those who suffer from a combination of social disadvantage, psychiatric disorder, and poor perceived health are more likely to experience an ataque de nervios. PMID- 8445375 TI - Risk factors for secondary depression among Mexican Americans and non-Hispanic whites. Alcohol use, alcohol dependence, and reasons for drinking. AB - We evaluated demographic (age, gender, income), cultural (ethnicity, acculturation), clinical (alcohol use, alcohol dependence), and motivational (subjective reasons for drinking) potential risk factors for secondary depression in 372 persons with lifetime alcohol abuse or dependence (from a randomly selected community sample of 2393). Lifetime alcohol abuse or dependence increased the risk of major depression by a factor of approximately 2 to 7. Recent secondary depression was present in 2% to 18% of persons meeting criteria for alcohol use disorders. Low income, female gender, and among Mexican Americans, low acculturation were associated with increased risk of secondary depression. Persons with lifetime alcohol diagnoses who currently drank, but did not name relaxation as a reason for drinking, were also at higher risk for secondary depression. Drinking to forget was associated with increased risk of secondary depression among Mexican American alcoholics, but not among non Hispanic white alcoholics. Current abstinence was associated with greater risk among lifetime alcoholics born in Mexico, but not among those born in the United States. PMID- 8445376 TI - P300 indexes thought disorder in schizophrenics, but allusive thinking in normal subjects. AB - Loosening of thinking as assessed by the Object Sorting Test (OST) has been found in a percentage of normal subjects but in a higher percentage of schizophrenics, and is familially transmitted in both groups. Loosening of thinking in normal subjects is not associated with evidence of impaired function or increased psychopathology, and in recognition of this, it was termed allusive thinking rather than thought disorder. Both OST-assessed loosening and concreteness of thinking were found to be present independently in a high percentage of schizophrenics, so that both were considered to contribute to schizophrenic thought disorder. The presence of OST-assessed loosening in schizophrenics would, therefore, be predicted to correlate partially rather than totally with measures of schizophrenic thought disorder. It has been suggested that OST-assessed loosening in normal subjects is due to a genetically determined reduction in strength of an inhibitory process that limits the spread of activation of semantic associations and results in a predisposition to schizophrenia. The brain event-related potential P300, which is, in part, under genetic control, may index this inhibitory process. Therefore, it was predicted that in normal subjects, P300 would correlate with OST-assessed loosening of associations. If schizophrenic thought disorder is due to a further weakening of this inhibitory process, it can be predicted that P300 in schizophrenics correlates only weakly with OST-assessed loosening of thinking, but more strongly with schizophrenic thought disorder. In a study in which P300 was elicited using a difficult selective attention task with 15 unmedicated schizophrenics and 22 healthy subjects, all three predictions were supported. PMID- 8445377 TI - Denial and social desirability in clinical evaluations of alleged sex offenders. AB - Clinicians are increasingly being requested to evaluate alleged sex offenders. Denial of sex offenses and minimization of psychopathology is common in such patients. We studied the relationship between denial of deviant sexual behavior and minimization/exaggeration of problems (i.e., response bias) during clinical evaluations in 59 alleged sex offenders. The data indicated that patients who denied allegations of deviant sexual behavior showed significantly more minimization of problems than did admitters (p < .001), and patients who admitted allegations showed more exaggeration of problems than did deniers (p < .05). Response bias was significantly associated with a number of personality characteristics. In particular, alleged offenders who denied deviant sexual behavior were more likely to be defensive about undesirable personality characteristics and to minimize problems than were those who admitted to deviant sexual behavior. When defensive, alleged sex offenders were likely to minimize anxiety and personality disorders. The data support the forensic utility of psychological testing in the assessment of alleged sex offenders. PMID- 8445378 TI - A comparison of behavioral group therapy and individual behavior therapy in treating obsessive-compulsive disorder. AB - Outpatients with a primary DSM-III axis I diagnosis of obsessive-compulsive disorder (OCD: N = 93) were randomly assigned to one of three treatment groups: One group (N = 30) received 24 sessions of behavioral group therapy over a 12 week period; a second group (N = 31) received 24 individual behavior therapy sessions over the same treatment interval; and members of a control group (N = 32) received 24 individual sessions of progressive muscle relaxation. The Yale Brown Obsessive-Compulsive Scale was administered before treatment at 2-week intervals during treatment, and at 6-month follow-up to measure changes in distress caused by OCD symptoms. The Beck Depression Inventory and the Self Rating Anxiety Scale were also administered at pretreatment, posttreatment, and 6 month follow-up. Both individual and group interventions proved to be equally effective at reducing distress caused by OCD symptoms, general depression, and anxiety by the end of treatment, although patients in the individual behavior therapy condition demonstrated faster reductions in OCD symptom severity. Patients in the group and individual behavioral interventions were able to maintain their gains at 6-month follow-up. Implications of these findings for outpatient treatment are discussed. PMID- 8445379 TI - Cognitive and motor correlates of everyday functioning in early Huntington's disease. AB - The present study documents the prevalence of deficits in the ability to carry out a variety of activities of daily living in early Huntington's disease (HD), along with the associated neuropsychological and motor deficits. Eighty patients with HD were assessed with the Huntington's Disease-Activities of Daily Living Questionnaire (HD-ADL). Sixty-seven patients also completed a comprehensive assessment of cognitive and voluntary motor functioning and chorea. The latter measures were correlated with HD-ADL total score and with most HD-ADL items, but not with those items dealing with marital and family relationship adjustment. Findings suggest that psychomotor speed and the ability to regulate attention may be particularly important determinants of everyday functioning in mild HD. Consistent with previously reported observations, this appears to be true even after accounting for individual differences in the severity of chorea and voluntary motor impairment. PMID- 8445380 TI - Clinical symptomatology and etiological factors in obese and normal-weight bulimic patients: a retrospective case-control study. PMID- 8445381 TI - Neurological hard signs in schizophrenia and major mood disorders. PMID- 8445383 TI - Development of the neural crest. PMID- 8445382 TI - Prognosis of depression in Down's syndrome. PMID- 8445384 TI - Cell lineage analysis in neural crest ontogeny. AB - The neural crest is a transitory and pluripotent structure of the vertebrate embryo composed of cells endowed with developmentally regulated migratory properties. We review here a series of studies carried out both in vivo and in vitro on the ontogeny of the neural crest in the avian embryo. Through in vivo studies we established the fate map of the neural crest along the neuraxis prior to the onset of the migration and we demonstrated the crucial role played by the tissue environment in which the crest cells migrate in determining their fate. Moreover, the pathways of neural crest cell migration could also be traced by the quail-chick marker system and the use of the HNK1/NC1 monoclonal antibody (Mab). A large series of clonal cultures of isolated neural crest cells showed that, at migration time, most crest cells are pluripotent. Some, however, are already committed to a particular pathway of differentiation. The differentiation capacities of the pluripotent progenitors are highly variable from one to the other cell. Rare totipotent progenitors able to give rise to representatives of all the phenotypes (neuronal, glial, melanocytic, and mesectodermal) encountered in neural crest derivatives were also found. As a whole we propose a model according to which totipotent neural crest cells become progressively restricted (according to a stochastic rather than a sequentially ordered mechanism) in their potentialities, while they actively divide during the migration process. At the sites of gangliogenesis, selective forces allow only certain crest cells potentialities to be expressed in each type of peripheral nervous system (PNS) ganglia. PMID- 8445385 TI - Restriction of neurogenic ability during neural crest cell differentiation. AB - Multipotent neural crest cells undergo developmental restrictions during embryogenesis and eventually give rise to the neurons and glia of the peripheral nervous system, melanocytes, and pheochromocytes. To understand how neuronal potential is restricted to a subpopulation of crest-derived cells, we have utilized sensitive markers of early neuronal differentiation to assess neurogenesis in crest-derived cell populations subjected to defined experimental conditions in vitro and in vivo. We describe environmental conditions that either (a) result in the irreversible loss of neurogenic potential over a characteristic time course or (b) maintain neurogenic potential among neural crest cells. PMID- 8445386 TI - Distribution of pluripotent neural crest cells in the embryo and the role of brain-derived neurotrophic factor in the commitment to the primary sensory neuron lineage. AB - Many early migratory neural crest cells are pluripotent in the sense that their progeny are able to generate more than one differentiated phenotype (Sieber-Blum and Cohen, 1980, Dev. Biol. 80:95-106; Baroffio, Dupin, and Le Douarin, 1988, Proc. Natl. Acad. Sci. USA 85:5325-5329; Bronner-Fraser and Fraser, 1988, Nature 335:161-164; Sieber-Blum, 1989a, Science 243:1608-1611; Ito and Sieber-Blum, 1991, Dev. Biol. 148:95-106). At trunk levels, the neural crest contains two classes (Sieber-Blum and Cohen, 1980) and at posterior rhombencephalic levels, three different classes of pluripotent cells (Ito and Sieber-Blum, 1991). We investigated cell differentiation by in vitro clonal analysis to determine when in development the pool of pluripotent neural crest cells becomes exhausted. The data suggest that different classes of pluripotent cells, precursor cells with more restricted developmental potentials, and apparently committed cells, exist at sites of advanced migration (posterior branchial arches) and even at target sites of neural crest cell differentiation [posterior branchial arches, dorsal root ganglia (DRG), sympathetic ganglia (SG), and epidermal ectoderm]. Some putative classes of pluripotent cells persist well into the second half of embryonic development. These observations have implications for our understanding of the mechanisms that control neural crest cell migration and differentiation. They support the idea that cues originating from the microenvironment affect differentiation of pluripotent neural crest cells. One such signal appears to be brain-derived neurotrophic factor (BDNF). In the presence of BDNF, but not nerve growth factor (NGF), there is a significant increase in the number of neural crest cells per colony that express a sensory neuron-specific marker. Because this increase is not accompanied by a corresponding increase in the total number of cells per colony, this suggests that BDNF plays a role in cell type specification. PMID- 8445387 TI - Cell fate determination in the peripheral nervous system: the sympathoadrenal progenitor. AB - Studies of postnatal chromaffin cells, sympathetic neurons and Small Intensely Fluorescent (SIF) cells have suggested that these cells develop from a common progenitor, the sympathoadrenal (SA) progenitor, whose fate is determined by the relative levels of nerve growth factor (NGF) and glucocorticoid (GC) in its environment (Unsicker et al., 1978, Proc. Natl. Acad. Sci. USA 75:3498-3502; Doupe et al., 1985a, J. Neurosci. 5:2119-2142). Recent studies have identified such a bipotential SA progenitor in the rat embryo. Surprisingly, this progenitor is initially unresponsive to NGF; neuronal differentiation is instead promoted by fibroblast growth factor (FGF). However, FGF appears to promote NGF responsiveness, suggesting that neuronal differentiation involves a relay or cascade of growth factor action. Furthermore, chromaffin cell differentiation appears to involve two sequential, GC-dependent events: the inhibition of neuronal differentiation and the induction of epinephrine synthesis. The former event is a prerequisite to the latter. Thus both the chromaffin and neuronal pathways of differentiation follow a series of dependent events, involving changes in the responsiveness of SA progenitors to environmental factors. Such changes correlate with changes in antigenic marker expression that can be observed in vivo. In addition to choosing between neuronal and endocrine fates, SA progenitors must also express an appropriate neurotransmitter phenotype. For example, sympathetic neurons can become either noradrenergic or cholinergic. This cholinergic potential is already present in uncommitted SA progenitors, as evidenced by their ability to synthesize acetylcholine. Recent studies suggest that these cells may have yet other developmental capacities, including the ability to synthesize serotonin. This capacity is consistent with the hypothesis that SA progenitors are closely related to progenitors of enteric neurons, an idea supported by recent observations using novel antigenic markers. The SA progenitor may be, therefore, a "master" neuroendocrine progenitor for the peripheral nervous system. PMID- 8445388 TI - From neural crest to bowel: development of the enteric nervous system. AB - The ENS resembles the brain and differs both physiologically and structurally from any other region of the PNS. Recent experiments in which crest cell migration has been studied with DiI, a replication-deficient retrovirus, or antibodies that label cells of neural crest origin, have confirmed that both the avian and mammalian bowel are colonized by emigres from the sacral as well as the vagal level of the neural crest. Components of the extracellular matrix, such as laminin, may play roles in enteric neural and glial development. The observation that an overabundance of laminin develops in the presumptive aganglionic region of the gut in ls/ls mutant mice and is associated with the inability of crest derived cells to colonize this region of the bowel has led to the hypothesis that laminin promotes the development of crest-derived cells as enteric neurons. Premature expression of a neuronal phenotype would cause crest-derived cells to cease migrating before they complete the colonization of the gut. The acquisition by crest-derived cells of a nonintegrin, nerve-specific, 110 kD laminin-binding protein when they enter the bowel may enable these cells to respond to laminin differently from their pre-enteric migrating predecessors. Crest-derived cells migrating along the vagal pathway to the mammalian gut are transiently catecholaminergic (TC). This phenotype appears to be lost rapidly as the cells enter the bowel and begin to follow their program of terminal differentiation. The appearance and disappearance of TC cells may thus be an example of the effects of the enteric microenvironment on the differentiation of crest-derived cells in situ. Crest-derived cells can be isolated from the enteric microenvironment by immunoselection, a method that takes advantage of the selective expression on the surfaces of crest-derived cells of certain antigens. One neurotrophin, NT-3, promotes the development of enteric neurons and glia in vitro. Because trkC is expressed in the developing and mature gut, it seems likely that NT-3 plays a critical role in the development of the ENS in situ. Although the factors that are responsible for the development of the unique properties of the ENS remain unknown, progress made in understanding enteric neuronal development has recently accelerated. The application of new techniques and recently developed probes suggest that the accelerated pace of discovery in this area can be expected to continue. PMID- 8445389 TI - Environmental influences on neural crest cell migration. AB - Neural crest cells migrate extensively and interact with numerous tissues and extracellular matrix components during their movement. Cell marking techniques have shown that neural crest cells in the trunk of the avian embryo migrate through the anterior, but not posterior, half of each sclerotome and avoid the region around the notochord. A possible mechanism to account for this migratory pattern is that neural crest cells may be inhibited from entering the posterior sclerotome and the perinotochordal space. Thus, interactions with other tissue may prescribe the pattern of neural crest cell migration in the trunk. In contrast, interactions between neural crest cells and the extracellular matrix may mediate the primary interactions controlling neural crest cells migration in the head region. PMID- 8445390 TI - Spatial integration among cells forming the cranial peripheral nervous system. AB - Neural crest cells represent a unique link between axial and peripheral regions of the developing vertebrate head. Although their fates are well catalogued, the issue of their role in spatial organization is less certain. Recent data, particularly on patterns of expression of Hox genes in the hindbrain and crest cells, have raised anew the debate whether a segmental arrangement is the basis for positional specification of craniofacial epithelial and mesenchymal tissues or is but one manifestation of underlying spatial programming processes. The mechanisms of positional specification of sensory neurons derived from the neural crest and placodes are unknown. This review examines the spatial organization of cells and tissues that develop in proximity to sensory neurons; some of these tissues share a common ancestry, others are targets of cranial sensory and motor nerves. All share the necessity of acquiring and expressing site-specific properties in a functionally integrated manner. This integration occurs in part by coordinating patterns of cell migration, as occurs between migrating crest cells and branchial arch myoblasts. Constant rostro-caudal relations are maintained among these precursors as they move dorsoventrally from the hindbrain paraxial regions to establish branchial arches. During this period the interactions among these and other mesenchymal cells are hierarchical; each cell population differentially integrates its past with cues emanating from new microenvironments. Analyses of tissue interactions indicate that neural crest cells play a dominant role in this scenario. PMID- 8445391 TI - The possible contribution of microglia and macrophages to delayed neuronal death after ischemia. AB - Macrophages have long been known to be involved in cytotoxic actions in many tissues in the body following infection. Knowledge of the post-injury actions of blood-borne macrophages in the brain, and their resident counterparts, the microglia, have been limited to the "mopping-up" of cellular debris. However, other functions are now coming to light and there is evidence that they contribute to both growth promotion and cytotoxicity following injury in the brain. This review raises the possibility that macrophages may contribute to delayed neuronal death following ischemia. Growth factors including certain cytokines produced by these cells protect against ischemia-induced neuronal death. In contrast, cytokines can also induce macrophages to synthesize nitric oxide synthase and indoleamine-2,3-dioxygenase which results in the production of the cytotoxins nitric oxide and quinolinic acid. It is hypothesized that viable cells produce or concentrate growth factors which prevent the induction of these enzymes, whereas damaged cells cannot. PMID- 8445392 TI - An enzymatic and immunochemical analysis of transketolase in fibroblasts from Wernicke-Korsakoff syndrome. AB - Transketolase in cultured skin fibroblasts from three patients with Wernicke Korsakoff syndrome (GM7504, 7505 and 7506) and matched controls was analyzed enzymatically and immunochemically with specific antisera generated against transketolase purified from human liver or red blood cells. The transketolase activity decreased by 45% in fibroblasts from the three Wernicke-Korsakoff patients, when compared to the activity in control cells. On immunoblots after SDS-PAGE, fibroblasts from the Wernicke-Korsakoff patients exhibited a 69-kDa species, a size similar to that of normal transketolase. The level of immunoreactivity was similar in the patient and control cells. The immunoblots of isoelectric focusing gels showed a major species of pI 8.6 with additional minor bands. However, the isoelectric focusing pattern of transketolase from the Wernicke-Korsakoff patients was also found in the majority of the control fibroblasts. Thus transketolase in fibroblasts from these Wernicke-Korsakoff patients is catalytically defective, but appears to be immunochemically normal. PMID- 8445393 TI - Stroke rates in patients with lacunar and large vessel cerebral infarctions. AB - A stroke registry was developed to determine the value of various clinical data in distinguishing lacunar from large vessel infarctions. Adequate localization was achieved in 98% of 246 patients with brain infarcts. These and 30 transient ischemic attack patients were followed for a median of 1082 days (range 2-1657). Follow-up data on TIA patients were invalidated by evidence of serious underreporting of TIAs in our general population. Among 212 male patients with cerebral infarcts not due to cardiogenic embolism, syphilis, migraine, vasculitis, or other unusual etiologies, 1-, 12-, and 36-month recurrence rates were 23%, 31% and 39% among patients with large vessel anterior circulation infarcts; 15%, 20% and 28% among patients with large vessel posterior circulation infarcts; and 8%, 16% and 21% among patients with lacunar anterior circulation infarcts, respectively. Six patients with posterior circulation lacunes did not experience recurrence. Comparative case fatality data were also compiled. Large vessel infarcts tended to be followed by further large vessel infarcts, usually in the same vascular distribution, whereas lacunar infarcts were not predictive of the type or location of subsequent events. PMID- 8445394 TI - Genetic characterization of a familial non-specific dementia originating in Jutland, Denmark. AB - Dementias with non-specific pathological changes are a relatively common but under diagnosed form of presenile dementia. A high proportion of reported cases are familial. We report on molecular genetic findings in the largest known pedigree with this syndrome. We have excluded the mutations known to cause familial prion disease, APP-linked familial Alzheimer's disease and candidate regions for Huntington's disease, other forms of Alzheimer's disease and motor neuron disease. We have demonstrated that familial non-specific dementia is a novel genetic dementia. PMID- 8445395 TI - Oscillatory potentials of visual evoked potentials using source derivation technique in rabbits. AB - The topographic distribution of epidurally recorded flashed visual evoked potentials (VEPs) in unanesthetized rabbits was studied using 2 montages. VEPs with linked ears reference and source derivation were compared. With the linked ears reference, N34 of VEPs which consisted of slow potentials and superimposed oscillations were recorded diffusely over the head. When source derivation was used, the slow negative potentials of N34 present on the recordings in P3 and P4 were not obtained in F3, Fz and F4. In a digital filtering study of the oscillatory potentials, N34 in oscillatory potentials which were recorded diffusely over the head were localized to the visual cortex by source derivation. It was concluded that N34 in the oscillatory potentials generated from the visual cortex are enhanced and localized with source derivation. PMID- 8445396 TI - Benign intracranial hypertension as a cause of transient partial pituitary deficiency. AB - A male patient is reported with benign intracranial hypertension, who presented with three periods of partial pituitary deficiency, corresponding to episodes of headaches and papilledema. No radiological signs of the empty sella syndrome were observed. Since benign intracranial hypertension has been implicated in the development of the empty sella syndrome, it is postulated that the endocrine deficiency syndrome encountered in the empty sella syndrome can be provoked by chronic intracranial hypertension in itself and is not necessarily secondary to the anatomical changes occurring in the sellar region. PMID- 8445397 TI - Factors associated with occurrence of large vessel and lacunar cerebral infarctions. AB - A stroke registry was developed to determine the localizing value of various clinical data. Adequate localization was achieved in 98% of 246 patients with infarcts. Among 212 male patients with cerebral infarcts not due to cardiogenic embolism or an unusual etiology, there were 152 with large-vessel and 59 with lacunar infarcts. Logistic regression analysis of factors associated with large vessel and lacunar stroke identified myocardial infarction on ECG as the only statistically significant variable; its presence was associated with an odds ratio for lacunar infarction of 0.19 (95% confidence interval 0.06-0.66) (P = 0.009). Logistic regression analysis of factors associated with anterior and posterior circulation large vessel stroke identified pack years of smoking as the only statistically significant variable; the odds ratio for posterior circulation infarction for a 10-year increment in pack years of smoking was 0.83 (95% confidence interval 0.73-0.94) (P = 0.0035). PMID- 8445398 TI - Saccades in internuclear ophthalmoplegia: are abduction disorders related to interocular disconjugacy? AB - We studied horizontal saccades by direct-current electro-oculography in 18 patients with internuclear ophthalmoplegia (INO), and in 16 healthy, age-matched subjects. The occurrence of abducting signs, i.e. overshoot and dissociated nystagmus, was related to an increase of interocular dissociation (measured by the ratio of abduction and adduction peak velocities). The amplitude of abduction hypermetria was strongly correlated with the intensity of adduction slowing. These findings support the idea of an adaptive mechanism underlying the overshoot and nystagmus of abduction saccades in INO. PMID- 8445399 TI - Sensory and sympathetic ganglia in HIV-1 infection: immunocytochemical demonstration of HIV-1 viral antigens, increased MHC class II antigen expression and mild reactive inflammation. AB - Sensory and sympathetic ganglia from 12 cases of human immunodeficiency virus type 1 (HIV-1) infection, all but one without clinical evidence of peripheral nerve disease, were studied immunocytochemically for their content of lymphocytes, macrophages, MHC Class II antigens and HIV-1 and cytomegalovirus antigens. They were compared with ganglia from 7 normal and peripheral nerve disease control cases. Compared with normal controls, many of the ganglia from the majority of HIV-1-infected subjects contained more T lymphocytes and macrophages and enhanced MHC class II expression. A few also showed occasional neuronal degeneration which was not present in the normal controls. In 7 cases HIV-1 gp41 envelope protein and/or p24 core protein antigens were detected in intraganglionic macrophages. Sensory ganglia contained more gp41 HIV-1 antigen than sympathetic ganglia. There was no clear correlation between detection of HIV 1 antigens in ganglia and in the CNS. Detection of HIV-1 antigens in ganglia was more common in cases of HIV-1 infection that had progressed to clinical AIDS by the time of death (71%) than in those that had not done so (40%). It is concluded that there is commonly a mild ganglionitis which is asymptomatic in the absence of detailed clinical testing and frequently associated with local presence of HIV 1 antigens in sensory and sympathetic ganglia in AIDS. PMID- 8445400 TI - Abnormalities of visual function in hereditary motor and sensory neuropathy. AB - Visual function was studied in a group of 15 patients with hereditary motor and sensory neuropathy (HMSN). Psychophysical measures of luminance and chromatic threshold and temporal contrast sensitivity were undertaken, together with visual evoked potentials (VEPs), visual fields and clinical neuro-ophthalmological examination. A patchy loss of visual function was found in individual cases of HMSN. In the group analysis there was evidence of a selective loss of luminance threshold and temporal contrast sensitivity at low temporal frequencies; the VEP P100 latency was not significantly prolonged. The losses of visual function in HMSN were discussed and compared with visual losses in multiple sclerosis, which had been detected using identical experimental techniques. PMID- 8445401 TI - Electroencephalographic changes in experimental autoimmune myasthenia gravis. AB - A number of reports have suggested that central disturbances of cholinergic function may occur in patients with myasthenia gravis. The present study was designed in order to examine cortical electroencephalographic (EEG) activity in Lewis rats with experimental autoimmune myasthenia gravis (EAMG). Experiments were performed on conscious rats with clinical EAMG and demonstrable antibodies against the acetylcholine receptor. The animals showed no gross changes in cortical EEG discharge in terms of cycles and durations of wake, desynchronized sleep, and synchronized sleep, as compared with control rats. However, abnormalities characterized by single spikes or waves, and by spike and wave complexes, were observed, most commonly during synchronization of the EEG. Use of computerized frequency analysis of the EEG records revealed the presence of three basic differences in EEG discharge in myasthenic animals: (1) additional high amplitude, low frequency (< 4 Hz) activity was recorded, especially during synchronized sleep; (2) decreases in mid-range (4-7 Hz) activity were recorded, particularly during periods of wakefulness; and, (3) increases in high frequency (> 8 Hz) spike discharge were observed at all times, although this was most evident during periods of synchronized sleep. The data provide further evidence for alterations in central cholinergic function in myasthenia gravis. PMID- 8445402 TI - Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) and diabetes mellitus: molecular genetic analysis and family study. AB - Two MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke like episodes) patients with diabetes mellitus (DM), and their family members are described clinically and genetically. The probands have the following features in common; normal early development, short stature, deterioration of intellectual ability, convulsions, cardiac conduction defect, sensorineural hearing loss, cortical blindness, and hemiparesis. Biochemical tests showed high levels of lactate and pyruvate in the blood and cerebrospinal fluid. Muscle biopsy showed ragged-red fibers. Molecular genetic analysis of both patients revealed that they had an A-to-G substitution at nucleotide position 3243 of the mitochondrial DNA in a heteroplasmic fashion. From these clinical and molecular genetic data they were diagnosed as having MELAS. In addition, fasting blood glucose levels were also high and they were diagnosed as having insulin-dependent DM. Some of the maternal family members in both cases also had insulin-dependent DM and several clinical symptoms of MELAS. DM and clinical features of MELAS were transmitted exclusively in the maternal line. In these cases, DM and MELAS might be a clinical manifestation of the same metabolic defect. PMID- 8445403 TI - Antiglycolipid antibodies, immunoglobulins and paraproteins in motor neuron disease: a population based case-control study. AB - The role of humoral autoimmune factors in the pathogenesis of motor neuron disease (MND) is currently under considerable scrutiny. In particular, there have been many reports of abnormal serum immunoglobulin patterns and elevated titres of anti-ganglioside antibodies in patients with MND. However, many of these studies may be biased by the selection criteria for patients and controls. In order to carefully address this issue we obtained 82 blood samples from consecutive MND patients identified through a national MND register in combination with 82 community controls matched for age, sex and geographical area. We used these samples to determine the frequency of monoclonal immunoglobulins (mIgs) and measure the levels of serum immunoglobulins and anti GM1 ganglioside antibodies in sporadic cases of MND in comparison with normal controls. Serum mIgs detected using high resolution and immunofixation agarose electrophoresis were present in 1.2% of MND patients and 2.4% of controls. Using a highly sensitive isoelectric focusing and immunoblotting method, monoclonal or oligoclonal immunoglobulins were found in 28% of MND patients and 27% of controls. Anti-GM1 antibodies were present in 26% of MND patients and 18% of controls (odds ratio = 1.5, 95%, CI 0.7-3.6) with no significant differences in titres between the 2 groups. Mean immunoglobulin G, A and M levels were equal in 2 groups. Thus, although alterations in these parameters were identified, we were unable to demonstrate any significant difference between MND patients and controls. We conclude that the majority of sporadic cases of MND are unlikely to have an autoimmune basis as judged by the lack of abnormalities in these parameters. PMID- 8445404 TI - The muscle silent period following transcranial magnetic cortical stimulation. AB - Transcranial magnetic stimulation (TMS) of the motor cortex during tonic muscle contraction produces a motor evoked potential followed by a silent period in the electromyogram. We sought to characterize the TMS induced silent period and to compare it to the silent period induced by supramaximal peripheral nerve stimulation. TMS was delivered to the motor cortex using a 9 cm diameter circular coil and the surface electromyogram was recorded from the contralateral abductor pollicis brevis muscle in six normal subjects. Increasing TMS stimulus intensity from 10 to 50% above threshold resulted in an increase in the duration of the silent period from a mean of 50 ms to 185 ms. Increasing the level of tonic muscle contraction from 5% of maximum to maximum resulted in a decrease in silent period duration from a mean of 155 ms to 133 ms. In contrast, the duration of the silent period following supramaximal median nerve stimulation showed greater shortening under similar conditions, from a mean of 160 ms at 5% of maximum contraction to 99 ms at 75% of maximum contraction. The TMS induced silent period was present during a TMS induced increase in the reaction time for a ballistic movement, the onset of movement being delayed until the end of the silent period. Peripheral nerve stimulation did not produce a delay in movement onset. The present findings favour a cortical origin for the TMS induced silent period, probably on the basis of intracortical inhibition, rather than peripheral inhibition of spinal motoneurones which is considered to be the basis for the silent period following peripheral nerve stimulation. PMID- 8445405 TI - Neuropsychological function before and after plasma exchange in myasthenia gravis. AB - This study was designed to determine whether there are cognitive and memory impairments in patients with myasthenia gravis (MG). Five female patients with MG were tested on two occasions, 4-6 days apart, prior to plasma exchange and after plasma exchange. All subjects had 2-4 separate plasma exchanges. The subjects were tested with mini-mental state examination (MMS), Zung self-rating depression scale (SDS) and a logical memory test. The MG group was significantly impaired compared to the control group on all tests prior to plasma exchange. The MG patients improved in motor function with plasma exchange. In addition, the mean MMS score improved from 26.4 to 28.2 and the mean SDS score improved from 0.46 to 0.39 and the mean immediate logical memory score improved from 5.8 to 8.4 and mean delayed logical memory score improved from 5.8 to 8.0. These improvements were all significant (P < 0.05). The results support the hypothesis that MG has central cholinergic effects, manifested by cognitive dysfunction. PMID- 8445406 TI - Treatment of cerebrotendinous xanthomatosis with low-density lipoprotein (LDL) apheresis. AB - We studied the effects of LDL-apheresis on the biochemical and clinical abnormalities of 5 patients with cerebrotendinous xanthomatosis (CTX). Levels of both cholestanol and cholesterol decreased to approximately 60% of those of pretreatment after one perfusion and gradually returned to their initial levels within 2 weeks. Improvement of clinical manifestations and regression of Achilles tendon xanthomas were detected after several perfusions, though dramatic changes could not be recognized. EEG abnormalities were improved immediately after LDL apheresis in one patient. We conclude that LDL-apheresis may affect the serum cholestanol level and clinical manifestations in patients with CTX. PMID- 8445407 TI - Fibroblasts are required for Schwann cell basal lamina deposition and ensheathment of unmyelinated sympathetic neurites in culture. AB - The ability to purify and recombine populations of peripheral neurons, Schwann cells and fibroblasts in tissue culture has enabled us to examine the contribution of fibroblasts to Schwann cell basal lamina assembly and ensheathment of unmyelinated rat superior cervical ganglion neurites in vitro. Purified perinatal superior cervical ganglion neurons were grown in culture either with Schwann cells or with Schwann cells plus fibroblasts derived from either superior cervical ganglion capsule or cranial periosteum. The cultures were maintained for 2-8 weeks on a collagen substratum in a medium known to promote Schwann cell differentiation (myelin, basal lamina formation) in the presence of dorsal root ganglion neurons. The extent of Schwann cell differentiation (ensheathment, basal lamina formation) in the presence of superior cervical ganglion neurons was evaluated in this study using electron microscopy. In superior cervical ganglion neuron plus Schwann cell cultures (without fibroblasts), Schwann cells achieved only a moderate degree of ensheathment; also, Schwann cell basal lamina was discontinuous and extracellular collagen fibrils were sparse. Although only discontinuous basal lamina was demonstrable by electron microscopy in these cultures, surprisingly, Schwann cell/neurite fascicles were uniformly immunostained for laminin, type IV collagen, and heparan sulfate proteoglycan. The addition of fibroblasts to superior cervical ganglion neuron plus Schwann cell cultures increased the deposition of basal lamina around the Schwann cell/neurite units, the number of collagen fibrils, and the extent of neurite ensheathment. We propose that the presence of basal lamina increases the Schwann cell's ability to ensheathe superior cervical ganglion neurites, possibly through an augmentation of specific extracellular matrix components or by increasing in some way the capacity of these components to become organized into basal lamina. We conclude that, unlike dorsal root ganglion neurons, superior cervical ganglion neurons are unable to stimulate full Schwann cell extracellular matrix expression with the result that these Schwann cells require the extraneuronal influence of fibroblasts to deposit basal lamina and attain their mature phenotype in culture. PMID- 8445408 TI - Freeze-fracture characterization of cell types at the surface of the taste organ of the frog, Rana esculenta. AB - The ultrastructure and distribution of intramembrane particles in the chemoreceptor surface of the frog taste organ have been studied by means of freeze-fracture. Sustentacular, wing, mucous cells and two different types of putative taste cells were found to reach the free surface of this chemoreceptor. Each of these cell types was characterized by a different pattern and density of intramembrane particles in the free surface. Wing cells displayed a relatively low number of large intramembrane particles (11.1 +/- 1.4 nm in diameter). Particles of similar size were also present in a much higher concentration in the membrane of cylinder-ending putative taste cells. In microvilli-ending putative taste cells, mucous cells, and sustentacular cells, small intramembrane particles were observed (6.8 +/- 0.78, 6.9 +/- 1.3, 7.2 +/- 0.7 nm in diameter, respectively). The density of these particles was higher in the sustentacular cells than in the other two cell types. These data provide evidence that there are two morphologically distinct types of putative taste cells in the frog taste organ, demonstrating that they are characterized by different pattern of intramembrane particles in their free surface. Furthermore, the present results support previous findings indicating that wing and sustentacular elements represent two different cell types. PMID- 8445409 TI - Spinule-type neurite outgrowth from horizontal cells during light adaptation in the carp retina: an actin-dependent process. AB - Dendrites of horizontal cells in the carp retina which invaginate the cone pedicles form numerous spinules during light adaptation. We have analyzed the contribution of cytoskeletal elements to this process. Isolated horizontal cells and frozen sections were screened with phalloidin for the existence of F-actin. F actin was present in all types of horizontal cells and particularly enriched in the distal parts of the dendrites. Electron microscopical analysis demonstrated that interruption of the F-actin polymerization with cytochalasin B inhibited the formation of spinules during light adaptation. The persistence of spinules was also affected. Cytochalasin B also prevented the light-independent, phorbol ester induced formation of spinules. Cytochalasin B only affected the morphology of the lateral, spinule-forming dendrites of cone horizontal cells within the cone pedicles, leaving the central, non spinule-forming dendrites of cone horizontal cells and the processes of rod horizontal cells within rod spherules unaffected. Whereas cytochalasin B prevented the protrusion of spinules, the spinule associated membrane densities were only slightly affected. The two main characteristics of spinules, protrusion and membrane densities are therefore independently regulated processes. PMID- 8445410 TI - Synaptophysin has a selective distribution in early endosomes of PC12 cells. AB - We have studied the endocytic pathway in PC12 cells and localized synaptophysin to a subpopulation of early endosomes. Endocytosis was examined by electron microscopy using horseradish peroxidase as an endocytic tracer. Immediately following brief incubations with horseradish peroxidase, label was seen in small vesicles and tubules which appeared to be part of the tubular early endosomal network. A large vacuolar structure, containing a rim of horseradish peroxidase reaction product and an electron-lucent central region, was also labelled at the earliest time point examined. Within 5 min after the horseradish peroxidase pulse, reaction product was seen in multivesicular bodies. After prolonged chase periods, horseradish peroxidase label was lost from the early endosomal structures and accumulated in large dense vesicles containing lamellar stacks of membranes. The observed pattern of horseradish peroxidase distribution is consistent with delivery of the tracer into tubular and vacuolar early endosomes with subsequent movement of horseradish peroxidase out of these compartments and into lysosomes. Examination of synaptophysin distribution by EM immunocytochemistry following incubations with horseradish peroxidase revealed selective immunogold labelling of early endosomal structures. Notably, small vesicular and tubular profiles were frequently double-labelled while vacuolar early endosomes were only rarely labelled for synaptophysin. Immunocytochemical labelling was not observed in multivesicular bodies or large dense vesicles with lamellar stacks. Results of experiments in which endosomal structures were immunoprecipitated with antibody to synaptophysin were consistent with the immunocytochemical findings. Maximal recovery of endocytosed horseradish peroxidase activity was seen immediately following the horseradish peroxidase pulse, and a significant decrease was seen after brief chase periods. These results indicate the presence of synaptophysin in vesicles and tubules of the early endosomal compartment. PMID- 8445411 TI - Vaccine adjuvant therapy for colorectal cancer: "very dramatic" or ho-hum? PMID- 8445412 TI - MVAC for bladder cancer: time to move forward again. PMID- 8445413 TI - Adjuvant active specific immunotherapy for human colorectal cancer: 6.5-year median follow-up of a phase III prospectively randomized trial. AB - PURPOSE: Patients with colon or rectal cancer were entered onto a prospectively randomized, controlled clinical trial of active specific immunotherapy (ASI) with an autologous tumor cell-bacillus Calmette-Guerin (BCG) vaccine. We investigated whether ASI could improve disease-free status and survival. PATIENTS AND METHODS: Ninety-eight patients with Dukes' stage B2-C3 colon or rectal cancer were randomized into groups treated by resection alone or resection plus ASI. Eighty patients met all eligibility criteria. All patients with rectal cancer were to receive 50 Gy of pelvic irradiation. Analysis of distribution of survival and disease-free survival was made on all eligible patients until December 31, 1990. RESULTS: As a single study, no statistically significant differences were detected in survival or disease-free survival for all 80 eligible patients. However, since it was recognized at the outset that there were treatment differences, in that rectal cancer patients were to receive postimmunotherapy radiation, it was considered that a cohort analysis of the colon and rectal cancer patients might be informative. With a median follow-up of 93 months, there is a significant improvement in survival (two-sided P = .02; hazards ratio, 3.97) and disease-free survival (two-sided P = .039; hazards ratio, 2.67) in all eligible colon cancer patients who received ASI. With a median follow-up of 58 months, no benefits were seen in patients with rectal cancer who received ASI. CONCLUSION: This study suggests that ASI may be beneficial to patients with colon cancer. PMID- 8445414 TI - Effect of relative cumulative dose-intensity on survival of patients with urothelial cancer treated with M-VAC. AB - PURPOSE: To evaluate the received dose-intensity in a mature data set of patients with advanced urothelial cancer who received at least one cycle of the methotrexate (M), vinblastine (V), Adriamycin ([A], doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (C) regimen (M-VAC). PATIENTS AND METHODS: Received dose-intensity was evaluated over time by summing doses over cycles for each patient, cumulating treatment times, and assuming four cycles of chemotherapy were planned. Relative cumulative dose-intensity was then calculated for individual patients at the end of each cycle. To assess a relationship with survival, relative cumulative dose-intensity was then used as a time-dependent covariate in Cox regression. RESULTS: The median follow-up was 6 years and median survival 13.3 months, with 20 patients alive at the time of analysis. Out of a maximum of 1.0, the median relative dose-intensity for the M-VAC combination decreased from .69 to .59 from cycle 1 to cycle 4. Similarly, a decrease from .68 to .62 and from .80 to .72 was observed for A and C, respectively. The median received dose-intensity for A was 6.0 mg/m2/wk, and for C 14 mg/m2/wk. Neither the four-cycle relative cumulative dose-intensity for the M-VAC combination, nor the relative cumulative dose-intensities for A or C were found to be significant prognostic factors. CONCLUSION: The absence of an effect for received dose intensity on survival may reflect the low dose-intensities of the components of the regimen actually delivered in this study. The results question whether the individual agents can be escalated sufficiently, with growth factor support, to improve significantly complete response proportions, a prerequisite for increasing the proportion of long-term survivors. PMID- 8445415 TI - Second cancer risk following testicular cancer: a follow-up study of 1,909 patients. AB - PURPOSE: Improved survival in testicular cancer has been accompanied by concern about long-term side effects of therapy. We assessed the evolution of second cancer (SC) risk over a prolonged follow-up period, which has been rarely studied in large patient series. PATIENTS AND METHODS: We estimated the risk of SCs in 1,909 patients with testicular cancer diagnosed in the Netherlands from 1971 to 1985. Complete medical information was obtained up to at least January 1988 for 92% of patients. Median follow-up was 7.7 years. For 89% of second tumors the diagnosis was confirmed through review of histologic slides; for an additional 8%, the diagnosis was verified by pathology reports only. RESULTS: Seventy-eight patients developed a SC 1 year or more after start of treatment, as compared with 47.6 expected on the basis of incidence rates in the general population (relative risk [RR], 1.6; 95% confidence interval [CI], 1.3 to 2.1). The mean 15-year actuarial risk of all SCs was 9.8% (95% CI, 7.5% to 12.8%). Significantly increased RRs were observed for all gastrointestinal cancers combined (RR, 2.6; 95% CI, 1.7 to 3.9), stomach cancer (RR, 3.7; 95% CI, 1.8 to 6.8), contralateral testicular cancer (CLTC) (RR, 35.7; 95% CI, 21.8 to 55.2), and leukemia (RR, 5.1; 95% CI, 1.4 to 13.0). Patients who had received irradiation to the paraaortic lymph nodes and who survived testicular cancer for more than 5 years were at particularly high risk of developing stomach cancer (RR, 6.9; 95% CI, 3.3 to 12.7). The median interval between the diagnosis of testicular cancer and stomach cancer was 12.4 years. Patients treated with chemotherapy (CT) did not experience an increase in SCs in general. Indeed, CT-treated patients, as compared with those who received radiotherapy (RT), or surgery alone, had significantly reduced risk of CLTC. This finding might be attributed to an eradicating effect of CT on carcinoma in situ or subclinical CLTC. The excess risk of leukemia was not found to be clearly related to CT. CONCLUSION: Testicular cancer patients who receive RT experience elevated risk of gastrointestinal tumors. CT does not seem to increase SC risk and may even decrease the risk of a CLTC. Following testicular cancer, the 15-year actuarial risk of all SCs is only about half the risk experienced by patients with Hodgkin's disease. PMID- 8445416 TI - Phase II trial of postoperative adjuvant intraperitoneal cisplatin and fluorouracil and systemic fluorouracil chemotherapy in patients with resected gastric cancer. AB - PURPOSE: This study was performed to assess the short- and long-term toxicities and the impact on relapse pattern and survival of postoperative intraperitoneal (IP) cisplatin and fluorouracil (FU) plus systemic intravenous (IV) FU as adjuvant therapy for gastric cancer patients who are at high risk for recurrence after potentially curative resection (T2N1-2M0 or T3-4N(any)M0). PATIENTS AND METHODS: Starting 14 to 28 days after potentially curative resection of primary gastric cancers, 35 patients were given IP cisplatin 25 mg/m2 and FU 750 mg daily for 4 days; FU 750 mg/m2 was concurrently given as a continuous 24-hour i.v. infusion. Five cycles of therapy delivered at 1-month intervals were used. RESULTS: After a median follow-up of 24 months, 51% of patients remain alive and free of disease. Sixteen patients have recurred; 13 of 16 had an intraabdominal component, whereas three had extraabdominal failure only. Two major treatment related toxicities were noted: neutropenia and a late toxicity of peritoneal fibrosis (sclerosing encapsulating peritonitis [SEP]). There was one postoperative death. Eleven patients underwent second laparotomy: five patients had SEP, two patients had bowel obstruction from adhesions unrelated to SEP, and four patients had recurrent cancer. Potential causes of SEP included an alkaline pH of infused FU and cisplatin that possibly led to activation of cisplatin before infusion. CONCLUSION: IP cisplatin and FU and concurrent systemic FU is a tolerable adjuvant therapy in the postoperative setting for patients with resected gastric cancer. The recommended dosage schedule with this technique is cisplatin 25 mg/m2 and FU 750 mg total dose IP with FU 500 mg/m2 as a continuous 24-hour infusion daily for days 1 to 4. SEP as a late toxicity, which was observed in 15% of patients, is treatable by surgical lysis of adhesions. PMID- 8445417 TI - Secondary cytoreduction for ovarian cancer following cisplatin therapy. AB - PURPOSE: This study was undertaken to evaluate the efficacy of secondary surgical cytoreduction in the management of ovarian cancer. PATIENTS AND METHODS: The cases of 100 patients with recurrent or progressive epithelial ovarian cancer whose initial treatment had been cytoreduction followed by cytotoxic therapy with a cisplatin-based regimen were reviewed. All 100 patients underwent surgery, after recurrence or progression was documented preoperatively, by gynecologic oncologists at the Mount Sinai Medical Center, New York, NY, between 1980 and 1991 with the intention of performing radical tumor reduction. RESULTS: Sixty-one patients had a secondary cytoreduction that left residual disease less than 2 cm in diameter. The median survival, determined from the date of the secondary cytoreduction to the date of death or last follow-up, is 27.1 months in the optimally treated group and 9.0 months for the 39 patients whose surgery was suboptimal (P = .0001). Other variables associated with statistically significant longer survival, and a significantly higher probability of achieving a successful secondary cytoreduction, included age < or = 55 years at the time of secondary cytoreduction, interval from initial diagnosis to secondary cytoreduction of more than 12 months, residual disease at initial staging laparotomy of less than 2 cm, and a complete clinical response to a cisplatin-based front-line regimen. Multivariate analysis confirms the survival benefit provided by a successful secondary cytoreduction when adjusted for the above variables. There was one postoperative mortality. Ten percent of the successfully cytoreduced patients and 18% of the unsuccessfully cytoreduced patients experienced some degree of postoperative morbidity. CONCLUSION: These data justify the performance of secondary cytoreductive surgery for patients who develop gross recurrent or progressive ovarian cancer following cisplatin therapy. PMID- 8445418 TI - A randomized trial comparing single-agent carboplatin with carboplatin followed by radiotherapy for advanced ovarian cancer: a North Thames Ovary Group study. AB - PURPOSE: To determine in a randomized trial of advanced ovarian carcinoma whether consolidation therapy with whole-abdominal radiotherapy (RT) after chemotherapy improves survival and disease-free survival compared with the continued chemotherapy. PATIENTS AND METHODS: Two hundred fifty-four patients with advanced epithelial ovarian cancer (stages IIB to IV) were entered onto a study of five monthly courses of 400 mg/m2 of carboplatin. One hundred seventeen patients with residual disease of 2 cm or less at second-look laparotomy or laparoscopy were then randomized to receive consolidation therapy, either five further courses of carboplatin at the same dosage or whole-abdominal RT (24 Gy). There was no control arm. RESULTS: Chemotherapy was well tolerated and was usually administered on an outpatient basis. Myelosuppression that was sufficient to delay chemotherapy occurred in only 3% of 1,418 courses analyzed. The main toxicity of carboplatin was nausea and vomiting, but this was easier to control than that with cisplatin. Although RT was well tolerated in the majority of the 58 patients, one patient who had been found to have multiple adhesions at second look surgery developed fecal fistulae post-RT that resulted in the patient's death from peritonitis. Median survival for the whole group from date of surgery was 25 months. No statistical difference was found in either survival or disease free survival between those patients who received consolidation chemotherapy and those who were treated with abdominal RT. Prognostic factors used to assess survival were stage, histology, amount of residual disease after primary surgery, and presence of tumor at second-look surgery. CONCLUSION: There seems to be no significant advantage for consolidation whole-abdominal RT compared with the continuation of the same chemotherapy in the management of advanced epithelial carcinoma of the ovary, even when no macroscopic residual disease is apparent at second-look surgery. PMID- 8445419 TI - Osteogenic sarcoma with clinically detectable metastasis at initial presentation. AB - PURPOSE: Chemotherapy and surgery have improved the length of survival for patients with osteogenic sarcoma (OS) who present without metastatic disease. We reviewed our experience with patients with OS who presented with clinically detectable metastasis to determine the prognostic factors and the effects of surgery on the primary tumor and on metastatic disease. PATIENTS AND METHODS: From 1975 to 1984 we treated 62 patients who had previously untreated OS with metastasis detected at presentation. All of these patients received intensive chemotherapy that included high-dose methotrexate; doxorubicin; and bleomycin, cyclophosphamide, and dactinomycin (BCD). Selected patients also received cisplatin. The intent of surgery was resection of the primary tumor and metastatic disease. RESULTS: Survival was extremely poor; only 11% of patients survived, with a median survival of 20 months. Survival was not affected by use of preoperative chemotherapy versus immediate surgery, and did not correlate with serum lactate dehydrogenase (LDH) level, alkaline phosphatase level, or the site of the primary tumor. Survival did correlate with age, location of metastatic disease, histologic response to preoperative chemotherapy, and completeness of surgical resection of all sites of tumor. Resection of all sites of tumor identified at initial presentation was necessary for survival. CONCLUSION: OS that presents with metastatic disease has a very poor prognosis with therapy, although therapy has achieved good results for patients without metastasis detected at diagnosis. Aggressive surgical resection of tumor is necessary for survival. The use of novel therapies at initial presentation is justified with this group of patients. PMID- 8445420 TI - Adjuvant randomized trials of doxorubicin/cyclophosphamide versus doxorubicin/cyclophosphamide/tamoxifen and CMF chemotherapy versus tamoxifen in women with node-positive breast cancer. AB - PURPOSE: We report two randomized trials of adjuvant systemic therapy in 747 patients < or = 65 years of age with histologically proven node-positive breast cancer. PATIENTS AND METHODS: Patients were selected for the two trials on the basis of lymph node and hormone receptor status. The only stratification was based on the treating institution. In patients with a lower probability of recurrence (n = 276), a comparison between endocrine therapy (tamoxifen [Tam] 30 mg/d for 2 years) and chemotherapy (cyclophosphamide, methotrexate, and fluorouracil [CMF] intravenously [IV], six cycles every 4 weeks) was performed. In patients with a higher risk of recurrence (n = 471), a comparison between chemotherapy alone (doxorubicin plus cyclophosphamide [AC] i.v., eight cycles every 3 weeks) and the same chemotherapy plus Tam was made. RESULTS: Overall, we found that CMF and Tam are equally effective in a subgroup of patients with a relatively good prognosis (low-risk patients). However, in the subset of women < or = 49 years old, a significantly greater disease-free survival (DFS) rate (P = .01) and overall survival (OS) rate (P = .002) was observed following therapy with CMF compared with Tam. In patients > or = 50 years old, the opposite was found, and Tam appeared to be superior to CMF (DFS, P = .003; OSm P = .5). These results must be interpreted cautiously, since a post-hoc stratification of patients by age (< or = 49, > or = 50) was performed, and significantly more younger, low-risk patients were randomized to receive chemotherapy alone and more older patients to receive Tam alone. Among patients with a relatively poor prognosis (high-risk patients), a combination of AC plus Tam was equivalent to AC and, when women were analyzed by age, this was found to be true of patients < or = 49 years as well. However, the addition of Tam to AC in women age > or 50 years resulted in a statistically significantly higher DFS (P = .01) and a trend toward better OS compared with women who received AC alone. CONCLUSION: Further trials are required to analyze the role of combined simultaneous or sequential chemoendocrine adjuvant treatment or each single therapy alone in defined risk adapted subsets of node-negative and node-positive patients. PMID- 8445421 TI - Ifosfamide and mitoxantrone as first-line chemotherapy for metastatic breast cancer. AB - PURPOSE: A phase II trial was performed to evaluate the efficacy and toxicity of a combination of ifosfamide (IFX) and mitoxantrone (MXN) as first-line chemotherapy for metastatic breast carcinoma. PATIENTS AND METHODS: Between January 1990 and August 1991, 48 patients with metastatic breast cancer were entered onto the study. Therapy consisted of IFX 2 g/m2 given as a 1-hour intravenous (IV) infusion on days 1 to 3; mesna 400 mg/m2 as an IV bolus immediately before and 4 hours after IFX administration and 2,000 mg orally 8 hours after IFX administration on days 1 to 3; and MXN 12 mg/m2 as an i.v. bolus on day 3. Cycles were repeated every 21 days until progressive disease (PD) or severe toxicity developed. RESULTS: One patient was considered not assessable for response. Objective regression (OR) was observed in 28 of 47 patients (60%; 95% confidence interval, 46% to 74%). Six patients (13%) had a complete response (CR) and 22 (47%) had a partial response (PR). The median time to treatment failure for the whole group was 9 months (range, 1 to 28); median survival was 19 months (range, 2 to 28). There were no treatment-related deaths. The limiting toxicity was myelosuppression. Leukopenia occurred in 37 patients (77%) and was grade 3 or 4 in 19 patients (40%). Nausea and vomiting were observed in 38 patients (80%), mucositis in 16 patients (33%), and grade 2 hematuria in two patients (4%). Eight patients (16%) developed mild neurotoxicity. CONCLUSION: The combination of IFX plus MXN is an active regimen against metastatic breast cancer with moderate toxicity that deserves further evaluation. PMID- 8445422 TI - Influence of treatment schedule on toxicity and efficacy of cyclophosphamide, epirubicin, and fluorouracil in metastatic breast cancer: a randomized trial comparing weekly and every-4-week administration. AB - PURPOSE: To compare the effect on toxicity and efficacy of the fluorouracil 500 mg/m2, epirubicin 60 mg/m2, and cyclophosphamide 500 mg/m2 (FEC) regimen divided into 4 weekly doses with conventional every-4-week administration in metastatic breast cancer. PATIENTS AND METHODS: The inclusion criteria demanded measurable or assessable metastases from breast cancer and a World Health Organization (WHO) performance index of 2 or less. One hundred seventy-three patients with metastatic breast cancer who had not been treated with anthracyclines were randomized to receive FEC once every 4 weeks or once a week. The scheduled monthly doses of the cytotoxic agents were identical in both groups. Three patients were excluded from analysis. RESULTS: Hematologic toxicity, alopecia, nausea, and vomiting were significantly more severe in the group that received treatment every 4 weeks. The response rate was higher in the group that received FEC every 4 weeks than in the group treated weekly (47% v 30%, P = .02). Time to progression was significantly (P = .005) longer with every-4-week FEC treatment (median, 9.2 months v 5.4 months for weekly treatment). Patients in the group treated every 4 weeks lived significantly (P = .01) longer than patients treated weekly (median survival times, 21.2 months v 11.8 months, respectively). The actually delivered monthly dose levels and treatment duration were similar in the two groups. CONCLUSION: Both efficacy and toxicity of FEC were greater when treatment was administered every 4 weeks rather than once a week, despite identical dose intensity. PMID- 8445423 TI - Phase I/II trial of tamoxifen with or without fenretinide, an analog of vitamin A, in women with metastatic breast cancer. AB - PURPOSE: Considerable attention has been focused on the chemopreventive properties of fenretinide against carcinogen-induced rodent mammary cancer. Less is known about its direct antitumor effects. The combination of tamoxifen and fenretinide is more effective than tamoxifen or fenretinide alone in prevention of rat mammary cancer. However, the combined toxicity of tamoxifen plus fenretinide in humans is unknown. Therefore, we performed a phase I/II trial in women with estrogen receptor (ER)-positive or progesterone receptor (PR) positive, previously untreated metastatic breast cancer. PATIENTS AND METHODS: Groups of three patients received tamoxifen 20 mg/d, or tamoxifen plus fenretinide 100, 200, 300, or 400 mg/d. Patients who received fenretinide enjoyed a 3-day "drug holiday" every 4 weeks. Serum levels of fenretinide and its major metabolites were monitored. Patients were monitored for known toxicities of tamoxifen and vitamin A analogs, as well as for response. RESULTS: There were no significant adverse effects on renal, hepatic, hematologic, or lipid values. Nyctalopia, photophobia, cheilitis, and pruritus were not observed. Improvement or stabilization of disease occurred in 12 of 15 patients. CONCLUSION: We conclude that tamoxifen administered with fenretinide is nontoxic. Phase III trials of tamoxifen versus tamoxifen plus fenretinide are warranted. PMID- 8445425 TI - Pregnancy outcome in patients treated for Hodgkin's disease. AB - PURPOSE: This study attempted to determine the outcome of pregnancies in patients (or their partners) who were successfully treated for Hodgkin's disease and to assess the effect of treatment on the children of the treated parents. MATERIALS AND METHODS: A questionnaire was distributed to and personal interviews were conducted with patients who were of reproductive age at the time of treatment with consecutive protocols of radiotherapy, chemotherapy, or both. Those premenopausal patients (or the sexual partners of patients) who attempted to conceive after successful treatment constituted the study population. Fertility assessment was based only on those patients identified as desiring children. RESULTS: Among 391 adult patients, 221 patients (104 females and 117 males) of reproductive age were interviewed. Before treatment, 63 of the 221 patients had 135 pregnancies, which resulted in 118 children, 11 spontaneous abortions, five elective abortions, and one stillborn. After treatment, 94 patients (43 females and 51 males) actively attempted conception; 35 females and 25 partners of male patients had 84 pregnancies, which resulted in 68 living children. Among the 84 pregnancies, there were one premature birth at 29 weeks, three spontaneous abortions, 11 elective abortions, and two stillborn: one at 32 weeks and one set of twins. The children have been observed for a median of 11 years (minimum follow up > 4.5 years). Of those patients who desired children, 35 of 43 females became pregnant, whereas only 25 of the 51 partners of male patients became pregnant. At least five male patients with low sperm counts apparently fathered children. CONCLUSIONS: This study demonstrates that both men and women have the potential for fertility after treatment regardless of treatment modality. The partners of male patients who were treated with combined modality treatment had a lower frequency of pregnancy than did the female patients who attempted conception and their frequency of pregnancy was also lower than the general population. There was no apparent increase in complications of pregnancy, spontaneous abortions, or congenital abnormalities after treatment compared with pregnancies in this patient group before treatment or with pregnancies in the general population. PMID- 8445424 TI - Phase I trial of intravenous cyclosporine to induce graft-versus-host disease in women undergoing autologous bone marrow transplantation for breast cancer. AB - PURPOSE: We investigated if graft-versus-host disease (GVHD), which is associated with an antitumor effect, could be induced in women with advanced breast cancer by treatment with cyclosporine (CSA) following reinfusion of purged autologous marrow after treatment with high-dose chemotherapy and defined the toxicities of this approach. PATIENTS AND METHODS: Fifty-one women with advanced breast cancer responding to therapy were treated with escalating doses of CSA (1.0, 2.5, or 3.75 mg/kg/d) for 28 days following high-dose chemotherapy and autologous bone marrow transplantation and monitored for induction of GVHD and toxicity of therapy. RESULTS: GVHD was induced in a dose-dependent fashion in 14%, 68%, and 92% of patients at each dose level, respectively, a median of 15 days following autologous marrow reinfusion. GVHD was clinically mild and limited to skin. Toxicity was acceptable, with two deaths within 50 days of marrow reinfusion. Statistically significant increases in maximum creatinine and bilirubin levels were seen at all dose levels when compared with similarly treated historic controls who did not receive CSA. Time to last platelet transfusion was significantly delayed in patients treated at the highest dose. CONCLUSION: GVHD can be safely induced by treatment with CSA in women with advanced breast cancer who are receiving high-dose alkylating agents and autologous bone marrow transplantation. The toxicity of this approach is acceptable. Evidence of antitumor efficacy awaits further investigation. PMID- 8445426 TI - Donor leukocyte infusions for chronic myeloid leukemia relapsed after allogeneic bone marrow transplantation. AB - PURPOSE: Treatment options for patients with chronic myeloid leukemia (CML) who relapse after allogeneic bone marrow transplantation (BMT) are limited. Treatment with lymphocytes from the original marrow donor and the influence on the malignant clone was studied in these patients. PATIENTS AND METHODS: Seven patients with CML that had relapsed after BMT with T-cell-depleted grafts were treated. Six patients received leukocyte infusions from the original marrow donor. One patient received a second BMT with unseparated marrow from the same sibling donor. Chimerism was studied using erythrocyte and cytogenetic markers. Residual leukemic cells were monitored by cytogenetic analysis of the Philadelphia (Ph) chromosome and by polymerase chain reaction (PCR) of the breakpoint cluster region/Abelson (BCR-ABL) fusion gene. RESULTS: In five patients with hematologic relapse, the Ph chromosome disappeared 1 to 3 months after the leukocyte infusions. Cytogenetic analysis and in situ hybridization (ISH) showed only donor cells during further follow-up. Four to five patients became negative for the BCR-ABL translocation by PCR. Graft-versus-host disease (GVHD) always preceded response and was severe in two patients. One patient with cytogenetic relapse showed no response after leukocyte infusions. GVHD after second BMT was of moderate severity. One year after second BMT, PCR for the BCR ABL translocation was negative. CONCLUSION: Infusion of donor leukocytes is an effective treatment with a low mortality in patients with CML relapsed after BMT with a T-cell-depleted graft. Longer follow-up and more patients will be needed to know whether cure will be permanent. PMID- 8445427 TI - Prevention of CNS disease in intermediate-risk acute lymphoblastic leukemia: comparison of cranial radiation and intrathecal methotrexate and the importance of systemic therapy: a Childrens Cancer Group report. AB - PURPOSE: This study (Childrens Cancer Group [CCG]-105) was designed in part to determine in a prospective randomized trial whether intrathecal methotrexate (IT MTX) administered during induction, consolidation, and maintenance could provide protection from CNS relapse equivalent to that provided by cranial radiation (CXRT) in children with acute lymphoblastic leukemia (ALL) and intermediate-risk features. PATIENTS AND METHODS: We randomized 1,388 children with intermediate risk ALL to the two CNS regimens. They received either IT MTX at intervals throughout their course of therapy or CXRT (18 Gy) during consolidation with IT MTX during induction, consolidation, and delayed intensification. Systemic therapy was randomized to one of four treatment regimens derived from a regimen used by CCG in recent studies for this patient population and three more intensive regimens based on the Berlin-Frankfurt-Munster trials. RESULTS: Life table estimates at 7 years show a 93% and 91% CNS relapse-free survival rate for the CXRT and IT MTX groups, respectively. The corresponding event-free survival (EFS) rates are 68% and 64%. The differences are not significant. Patients who received more intensive systemic therapy had a 94% CNS relapse-free survival rate on either CXRT or IT MTX, while patients who received standard systemic therapy had 90% and 80% rates for CXRT and IT MTX, respectively (P < .0001). Patients less than 10 years of age who received CXRT or IT MTX had 72% and 71% EFS rates if they received more intensive systemic therapy. Patients 10 years or older who received CXRT had an improved EFS (61% v 53%) with a more intensive systemic program. This was primarily due to fewer bone marrow relapses (P = .04). CONCLUSIONS: IT MTX during induction, consolidation, and maintenance provides protection from CNS relapse in patients with intermediate-risk ALL equivalent to that provided by CXRT if more intensive systemic therapy is given. The CNS relapse rate with either CXRT or IT MTX is in part dependent on the associated systemic therapy. For intermediate-risk patients less than 10 years of age, IT MTX with an intensified systemic regimen provided CNS prophylaxis comparable to that provided by CXRT, whereas older patients had fewer systemic relapses if they received CXRT. PMID- 8445428 TI - Improved outcome with delayed intensification for children with acute lymphoblastic leukemia and intermediate presenting features: a Childrens Cancer Group phase III trial. AB - PURPOSE: The Berlin-Frankfurt-Munster (BFM) 76/79 trial of acute lymphoblastic leukemia (ALL) in children produced impressive disease-free survival (DFS) rates with a protocol that began with 8 weeks of intensive therapy, followed by 8 weeks of maintenance therapy, and then another 6 weeks of intensive treatment. The current study was conducted to determine the relative contributions of each of these periods of intense therapy on the DFS rates of ALL patients with intermediate presenting features. In addition, due to concerns regarding the toxicity of CNS irradiation, we compared cranial irradiation (CXRT) with intrathecal methotrexate (IT MTX) administered during induction and consolidation to IT MTX during all phases of the treatment program. PATIENTS AND METHODS: Between May 1983 and April 1989, more than 1,600 children with ALL and intermediate presenting features, as defined by the Childrens Cancer Group (CCG), were entered into a randomized trial that tested four systemic therapy regimens and two CNS programs. RESULTS: The results with a median follow-up of 57 months show that systemic regimens with a delayed intensification (Delint) phase of therapy had a 5-year event-free survival (EFS) rate of 73% compared with the control regimen EFS rate of 61% (p = .006). For children less than 10 years of age, standard three-drug induction and Delint produced a 77% 5-year EFS. IT MTX during all phases of therapy provided CNS protection comparable to the CXRT regimen in children less than 10 years of age. Children 10 years of age or older appear to have a better EFS rate with intensive induction, Delint, and CXRT. CONCLUSION: Delint improves the EFS rate of children with ALL and intermediate presenting features. Maintenance IT MTX can be safely substituted for CXRT for presymptomatic CNS therapy in children with intermediate-risk characteristics less than 10 years of age. PMID- 8445429 TI - Impact of high-dose cytarabine and asparaginase intensification on childhood acute myeloid leukemia: a report from the Childrens Cancer Group. AB - PURPOSE: The purpose of this review was to determine the impact of high-dose cytarabine and asparaginase intensification, administered shortly after remission induction, on the outcome of childhood acute myeloid leukemia (AML). MATERIALS AND METHODS: Three consecutive Childrens Cancer Group (CCG) trials of acute myeloid leukemia, CCG 251 (1979 to 1983), CCG 213P (1983 to 1985), and CCG 213 (1985 to 1989) with a total of 1,294 patients, were reviewed and provide the basis of this report. RESULTS: CCG 213P demonstrated the importance of dose interval, in that two courses of cytarabine and asparaginase administered at 7 day intervals gave superior 5-year survival rates (58% v 41% from the end of induction, P < .04) to the same therapy administered at 28-day intervals. CCG 213 showed that there was no advantage to the maintenance therapy used for patients who received two courses of cytarabine and asparaginase at 7-day intervals (5 year survival, 68% [no maintenance] v 44% [maintenance] from the end of consolidation, P < .01). Inclusion of the 7-day interval cytarabine/asparaginase intensification was accompanied by an overall improvement in 5-year survival rates from diagnosis when compared with historical controls (CCG 213, 36% v CCG 251, 29%, P < .02) although other differences between these studies could also be responsible for the improvement seen. CONCLUSION: High-dose cytarabine and asparaginase intensification eliminated the benefit of prolonged maintenance therapy in childhood AML and was accompanied by an overall improvement in survival. PMID- 8445430 TI - Molecular residual disease status at the end of chemotherapy fails to predict subsequent relapse in children with B-lineage acute lymphoblastic leukemia. AB - PURPOSE: We have investigated whether the extent of residual leukemia in the marrows obtained at the completion of chemotherapy can predict subsequent relapse in children with B-lineage acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Marrow samples of 24 patients were examined for residual disease at the end of treatment using a quantitative method based on the polymerase chain reaction (PCR) amplification of the complementarity determining region-3 of the immunoglobulin heavy chain. RESULTS: Of the 15 patients who remain in continuous bone marrow remission (range, 41 to 98 months), 14 had no detectable leukemic cells; one patient had a very low level (one in approximately 335,000 marrow cells) of residual leukemic cells that underwent clonal evolution. Among the nine patients who had a marrow relapse after the completion of treatment, eight patients whose relapses occurred 4 to 54 months from the end of therapy had no detectable leukemic cells, whereas only the one patient who relapsed 2 months after the completion of therapy had detectable residual disease. CONCLUSION: These observations indicate that the absence of detectable residual leukemia by PCR at the end of chemotherapy is not sufficient to assure that the patient is cured and suggest that frequent serial monitoring is required for the early prediction of relapse off therapy. PMID- 8445431 TI - Phase I study of escalating targeted doses of carboplatin combined with ifosfamide and etoposide in children with relapsed solid tumors. AB - PURPOSE: The tolerance of escalating targeted doses of carboplatin combined with ifosfamide (IFOS)/etoposide (VP-16) (ICE) was assessed in children with recurrent solid tumors. PATIENTS AND METHODS: To reduce interpatient variability in carboplatin systemic exposure, 45 children were treated with doses individualized to a target area under the serum concentration versus time curve (AUC) based on renal function, using technetium 99-diethyl-enetriamine pentaacetic acid (99mTc DTPA) clearance to estimate glomerular filtration rate (GFR). Cohorts of at least three patients received carboplatin at an initial target AUC of 2 mg/mL x min, with escalations of 1 mg/mL x min in subsequent cohorts. Courses consisted of carboplatin on day 1 followed by IFOS 2 g/m2 plus VP-16 100 mg/m2 on days 2 and 3. Patients received at least two courses, with a maximum of eight courses possible in the absence of progressive disease. When only moderate toxicity occurred after escalation to 5 mg/mL x min, a third dose of IFOS plus VP-16 was added. After three patients were treated at this level, carboplatin escalation proceeded. RESULTS: Neutropenia and thrombocytopenia were the dominant toxicities in the 43 assessable patients. At the target AUC of 8 mg/mL x min, 13 of 20 cycles were associated with febrile neutropenia. For phase II trials, we recommend a carboplatin target AUC of 6 mg/mL x min with three doses of IFOS and VP-16 for patients with prior craniospinal irradiation or high-dose cisplatin (CDDP)/VP-16, or 7 mg/mL x min for patients without such histories. There were two complete responses (CRs), 13 partial responses (PRs), and 17 objective responses (ORs). CONCLUSION: The ICE regimen shows promising activity in pediatric solid tumors. The clear relationship between hematologic toxicity and carboplatin systemic exposure supports the use of targeted dosing in further trials of ICE chemotherapy. PMID- 8445432 TI - Randomized prospective comparison of intraventricular methotrexate and thiotepa in patients with previously untreated neoplastic meningitis. Eastern Cooperative Oncology Group. AB - PURPOSE: This prospective randomized cooperative group study was conducted in patients with neoplastic meningitis treated with intrathecal methotrexate or thiotepa to assess response rates and survival, prognostic factors, and the toxicity of these regimens. PATIENTS AND METHODS: Fifty-nine adults with nonleukemic malignancies, performance status of 0 to 3, and positive CSF cytologies were assigned to receive intrathecal methotrexate (10 mg) or thiotepa (10 mg) twice weekly. Radiation, was administered to mass lesions and/or symptomatic sites and appropriate systemic therapy was given concomitantly. RESULTS: Fifty-two patients were assessable. Most were female (79%), nonambulatory (77%), had been pretreated with radiation (52%) and chemotherapy (77%), and had evidence of systemic disease (65%). Most primary cancers were of the breast (48%), lung (23%), or lymphatics (19%). Treatment arms were well balanced, except that more patients randomized to methotrexate had breast cancer (61% v 33%) and were without evidence of systemic cancer (21% v 4%). No patient had important neurologic improvement with therapy, and 75% deteriorated neurologically within 8 weeks of initiating therapy. Survival ranged from 4 days to 110.5+ weeks. Median survival for patients receiving methotrexate was 15.9 weeks and 14.1 weeks for patients treated with thiotepa. Factors predictive of shorter survival included progressive systemic disease (P = .0005), poor performance status (P = .03), and significant cranial nerve palsies (P = .02). Although serious toxicities were similar, mucositis (P = .04) and neurologic complications (P = .008) were more common in patients who received methotrexate. CONCLUSION: The efficacy and overall toxicities of intraventricular methotrexate and thiotepa seem similar and neither reverses fixed neurologic deficits. Early diagnosis and treatment and new therapeutic approaches are needed to improve the outcome for patients with neoplastic meningitis. PMID- 8445434 TI - Adjuvant therapy for breast cancer: understanding the overview. International Breast Cancer Study Group. PMID- 8445433 TI - The Functional Assessment of Cancer Therapy scale: development and validation of the general measure. AB - PURPOSE: We developed and validated a brief, yet sensitive, 33-item general cancer quality-of-life (QL) measure for evaluating patients receiving cancer treatment, called the Functional Assessment of Cancer Therapy (FACT) scale. METHODS AND RESULTS: The five-phase validation process involved 854 patients with cancer and 15 oncology specialists. The initial pool of 370 overlapping items for breast, lung, and colorectal cancer was generated by open-ended interview with patients experienced with the symptoms of cancer and oncology professionals. Using preselected criteria, items were reduced to a 38-item general version. Factor and scaling analyses of these 38 items on 545 patients with mixed cancer diagnoses resulted in the 28-item FACT-general (FACT-G, version 2). In addition to a total score, this version produces subscale scores for physical, functional, social, and emotional well-being, as well as satisfaction with the treatment relationship. Coefficients of reliability and validity were uniformly high. The scale's ability to discriminate patients on the basis of stage of disease, performance status rating (PSR), and hospitalization status supports its sensitivity. It has also demonstrated sensitivity to change over time. Finally, the validity of measuring separate areas, or dimensions, of QL was supported by the differential responsiveness of subscales when applied to groups known to differ along the dimensions of physical, functional, social, and emotional well being. CONCLUSION: The FACT-G meets or exceeds all requirements for use in oncology clinical trials, including ease of administration, brevity, reliability, validity, and responsiveness to clinical change. Selecting it for a clinical trial adds the capability to assess the relative weight of various aspects of QL from the patient's perspective. PMID- 8445435 TI - Dr Hoover responds to Dr Moertel. PMID- 8445436 TI - Dodging the dogma. PMID- 8445438 TI - All-trans-retinoic acid in acute promyelocytic leukemia: let's get on with finding out how good it is. PMID- 8445437 TI - Retinoids as anticancer agents. PMID- 8445439 TI - Secondary acute myeloid leukemia after autologous bone marrow transplantation for malignant lymphomas. PMID- 8445440 TI - Direction: standstill. PMID- 8445441 TI - Racial differences in late prenatal care visits. AB - The purpose of this study was to examine potential racial disparities in the use of prenatal care beyond what could be measured by the Kessner Index. The data were obtained from the 1986 Massachusetts Prenatal Care Survey, a follow-back study of 2587 postpartum women, which had as its primary objective the identification of barriers to adequate use of prenatal care. This investigation examined the number of prenatal visits reported for each month of pregnancy and found that white women reported significantly more visits than black women only in the eighth and ninth months of pregnancy. This racial difference remained after we controlled for gestational age, sociodemographic factors, reported barriers to care, payor status, and access to care. This study suggests that racial differences in use of late prenatal visits need direct attention if the gaps in use of prenatal care and adverse birth outcomes are to be lessened. PMID- 8445442 TI - Prevention of symptomatic patent ductus arteriosus with ethamsylate in babies treated with exogenous surfactant. AB - Some trials in premature infants with respiratory distress syndrome have shown an increased incidence of patent ductus arteriosus after exogenous surfactant therapy. The effect of prophylactic ethamsylate on patent ductus arteriosus after intratracheal administration of a single dose of porcine surfactant preparation (Curosurf, 2.5 ml/kg) was studied in a group of 20 preterm infants with severe respiratory distress syndrome. Gestational age of the patients was 29.2 +/- 2.5 weeks (mean +/- SD), and birth weight was 1158 +/- 319 gm. Ethamsylate (12.5 mg/kg) was given prophylactically within the first 4 hours of life followed by 6 hourly doses for 4 days. Hemodynamically significant patent ductus arteriosus occurred more frequently in the untreated group (8 of 10) than in the ethamsylate group (2 of 10) (p < 0.02). No acute adverse effects were attributed to the therapy. This preliminary experience suggests that ethamsylate, an inhibitor of prostaglandin biosynthesis, could be useful in reducing the incidence of patent ductus arteriosus in very low birth weight infants treated with exogenous surfactant. PMID- 8445443 TI - A case of aplasia cutis congenita in dizygotic twins. AB - We report a newborn infant with extensive aplasia cutis congenita of the flanks and thighs, associated with a co-twin fetus papyraceus. DNA restriction fragment polymorphism analysis of the twins proved dizygosity. The association of these two conditions in twins is reviewed. PMID- 8445444 TI - Neonatal Oral-Motor Assessment scale: a reliability study. AB - Feeding problems are frequently encountered in the neonatal intensive care unit as a result of the survival of greater numbers of preterm, medically fragile, and chronically ill infants. Such feeding problems have not, however, been well described. In an attempt to categorize the oral-motor patterns that underlie poor feeding in the neonatal period, a clinical assessment tool was devised that describes jaw and tongue function during nutritive sucking. The Neonatal Oral Motor Assessment Scale separates 13 characteristics of jaw movement and 13 characteristics of tongue movement into categories of normal, disorganized, and dysfunctional. This scale was administered to 40 infants to establish interrater reliability, revise the scale as necessary based on the reliability, and attempt to further qualify and describe patterns of disorganized and dysfunctional sucking in the neonatal period. PMID- 8445445 TI - Intrauterine fetal death: mediconursing and psychosocial considerations for the childbearing patient. AB - The purpose of this article is to provide the perinatal nurse with a current review of the pregnancy complication, intrauterine fetal death. The causes, associated complications, and mediconursing management of this pregnancy complication are reviewed. Additionally, by use of the Snyder childbearing trajectory model, the psychosocial effects of intrauterine fetal death are discussed. The presentation of the Snyder model is intended to provide the nurse with a conceptual framework through which psychosocial nursing interventions can be derived. PMID- 8445446 TI - Coping styles in women undergoing amniocentesis in the second trimester of pregnancy. AB - This descriptive study focused on coping styles used by women undergoing a first amniocentesis. The 60 women who participated in the study were undergoing amniocentesis in the second trimester of pregnancy. The women completed an instrument to determine coping styles at three points during the amniocentesis process. Results showed that coping strategies decreased over time. The participants consistently used problem-focused strategies with more frequency than emotion-focused strategies. PMID- 8445447 TI - An ethical dilemma in the neonatal intensive care unit: providing due care. AB - We have discussed the ethical principles of beneficence, nonmaleficence, fidelity, and justice as they relate to a case involving what to do when there are too many sick neonates in an NICU. The use of ethical principles clarified the issues surrounding the shift in power and the decision making. This clarification led to the various short-term and long-term strategies that were designed to resolve the ethical dilemma. In addition, analysis of this case demonstrates that issues related to justice frequently involve the making or the questioning of policy so that all can be treated in a fair way. Providing for individuals in a fair manner reduces the potential for harm. Focusing on ethical principles may serve to deemphasize and diffuse the control and territorial issues that may arise in similar cases. This refocusing will then enable all parties to address their common concern--how to provide due care to sick neonates and their families. PMID- 8445448 TI - Ethical issues in quadruple amputation in a child with meningococcal septic shock. PMID- 8445449 TI - Peritoneal dialysis in the neonatal period: outcome data. AB - Scant information exists on the prognosis of infants with renal failure who receive peritoneal dialysis in the first month of life. We reviewed the outcome of 23 such patients 1 year after the onset of renal failure. Diagnoses included acute tubular necrosis (11 infants), renal dysplasia (5), obstructive uropathy (4), polycystic kidney disease (1), renal vein thrombosis (1), and renal artery thrombosis (1). Seven of the eleven patients with acute tubular necrosis had had cardiac surgery. At 1 year, eight (35%) of the patients had died, six (26%) had a full recovery, seven (30%) were receiving long-term dialysis awaiting a transplant, and two (9%) had chronic renal failure. Effective dialysis, characterized by the reversal of metabolic disturbances or attainment of fluid balance, was accomplished in all patients. The mean duration of dialysis was 4.5 months (range, 0.1 to 12 months). The most common complications of dialysis were peritonitis and catheter exit site infection. Despite the provision of supplemental calories via nasogastric tube, the majority of patients receiving long-term dialysis showed impaired growth and mild developmental abnormalities. Peritoneal dialysis is an effective means of renal replacement therapy in the neonatal period; however, the morbidity and mortality rate for this population remains high. PMID- 8445450 TI - Neonatal surgery casebook. Congenital arterial aneurysm. PMID- 8445451 TI - Ventilatory management casebook. Neonatal respiratory failure: response to volume ventilation. PMID- 8445452 TI - Special imaging casebook. Posterior urethral valves. PMID- 8445453 TI - Fetal heart rate monitoring casebook. Fetal heart rate monitoring in diabetic ketoacidosis. PMID- 8445454 TI - Fibronectin levels in premature infants with late-onset sepsis. AB - Physical features do not reliably distinguish premature infants with bacterial infections from those with noninfectious conditions. We evaluated the association of depressed plasma fibronectin with sepsis among hospitalized very low birth weight infants (< 1500 gm). Reference values were determined by sequential plasma sampling from 60 healthy very low birth weight infants. Among 17 very low birth weight infants with proved late-onset sepsis (mean age, 20 days; range, 10 to 42 days), 9 had plasma fibronectin levels more than 1 SD below the age- and birth weight-associated mean. Overall, the sensitivity and specificity of the finding of depressed fibronectin levels were 53% and 94%, respectively. These data suggest that depression of plasma fibronectin occurs commonly in association with late-onset sepsis among hospitalized premature infants. PMID- 8445455 TI - Is this finally the beginning? PMID- 8445456 TI - An outrageous fortune. PMID- 8445457 TI - Retinoblastoma in the state of Oklahoma: a clinicopathologic review. AB - This is a retrospective review of 56 patients diagnosed with retinoblastoma (Rb) from 1970 to 1990 at either the Dean A. McGee Eye Institute or Children's Hospital of Oklahoma. Twenty-six (46%) patients had somatic Rb and thirty (54%) had germinal Rb. On average, somatic disease presented at 20.5 months and germinal disease at 11.7 months. Nine (16%) of our patients have died; of these, metastatic disease was the cause of death in six patients, whereas a midline pineal tumor (trilateral retinoblastoma) was the cause of death in three patients. Metastatic disease presented an average of 17.5 months after the diagnosis of Rb, and death occurred an average of 10.3 months after the diagnosis of metastasis. Trilateral Rb presented an average of 18 months after the diagnosis of retinoblastoma, and on average death occurred 2 months later. Histopathology was available on forty-nine of our patients. Poorly differentiated tumor histology, optic nerve invasion of tumor cells past the surgical plane of transection, and choroidal invasion of tumor cells appear to be significant histological markers for developing metastatic disease. The cytogenetics, current therapy, and related management of retinoblastoma are reviewed. PMID- 8445458 TI - Symposium on antimicrobial therapy. VI. The aminoglycosides. PMID- 8445459 TI - Human ehrlichiosis--an overview. AB - Canine ehrlichiosis, previously thought to be restricted to dogs, has gained prominence in the human population since 1986. In the United States, human ehrlichiosis is a newly recognized disease ranging from a mild infection to a severe life threatening or fatal disease. Since antibody titers were found to be highest to E. canis in human ehrlichiosis patients, it was believed that E. canis or a closely related species was the etiologic agent. Investigators from the Centers for Disease Control recently have isolated a bacterium believed to be the etiologic agent of human ehrlichiosis and proposed the name Ehrlichia chaffeensis. Human cases of the disease have been identified primarily in the southeastern and south-central areas of the United States. Although relatively few cases are diagnosed, Oklahoma, according to one source, has been found to have the highest incidence rate. The human disease could be misdiagnosed as Rocky Mountain spotted fever, murine typhus fever, or Q fever. PMID- 8445460 TI - Anencephalic organ donation in Oklahoma. Right problem, wrong answer. AB - The scarcity of donor organs results in the death of some pediatric transplant candidates while they wait for an organ. The use of anencephalic infants has been suggested as a way to increase the donor pool. Advantages and disadvantages of this approach are reviewed, and recommendations made for the state of Oklahoma. PMID- 8445461 TI - The glass ceiling of oral and maxillofacial surgery. PMID- 8445462 TI - Contemporary management of deep infections of the neck. AB - Odontogenic infections rarely lead to involvement of the lateral and retropharyngeal spaces. When this does occur, the microbiology of the infection is similar to the typical odontogenic infection, ie, Streptococcus and oral anaerobes including Peptostreptococcus, Bacteroides, and Fusobacterium. There is an increased incidence of Fusobacterium seen in the more severe infections, as well as a higher incidence of Streptococcus milleri. Many patients who have deep cervical infections also have some compromise in their host defense mechanism, such as diabetes. The signs and symptoms of deep cervical space infections are similar to those of the severe submandibular space infection, but also includes sialorrhea, respiratory distress, odynophagia, and dysphagia. Lateral soft-tissue radiographs of the neck are useful in assisting with the diagnosis of retropharyngeal infections, and CT scans can provide definitive information regarding lateral pharyngeal space involvement. Treatment includes the use of high-dose intravenous bacteriocidal antibiotics. The recommended antibiotics are penicillin-metronidazole, ampicillin-sulbactam, or clindamycin. Certain cephalosporins may also be useful in selected patients. Early surgical intervention is also indicated. Aggressive incision and drainage of all of the involved spaces is necessary to assure early resolution of the infection. Continual airway monitoring and the establishment of surgical airways is the final portion of the treatment triad. PMID- 8445463 TI - Use of sodium hyaluronate in treating temporomandibular joint disorders: a randomized, double-blind, placebo-controlled clinical trial. AB - This study assessed the efficacy of high-molecular-weight sodium hyaluronate as a treatment for certain intracapsular temporomandibular joint (TMJ) disorders. One hundred twenty-one patients were studied at three test sites using a randomized, double-blind, placebo-controlled experimental design. Patients were selected on the basis of 1) confirmed diagnosis of either degenerative joint disease (DJD), reducing displaced disc (DDR), or nonreducing displaced disc (DDN); 2) nonresponsiveness to nonsurgical therapies; and 3) severe dysfunction as established by the Helkimo indices (HI), visual analog scales (VASs), and physical measurements of joint movement and joint noise (arthrophonometry [APM]). Subjects received a unilateral upper joint space injection of either 1) 1% sodium hyaluronate in physiologic saline (MedChem Products, Woburn, MA) or 2) USP physiologic saline. Clinical evaluations were performed using HI, VAS, and APM at weekly intervals for the first month and then at monthly intervals up to 6 months postinjection. Statistical analyses for both categorical and continuous variables were performed for each diagnostic category at each examination interval. For DJD, no difference in outcome was seen between treatment groups. For DDN, significant between-group differences were seen through 1 month; however, beyond this time point, the number of DDN patients was insufficient to draw meaningful conclusions concerning efficacy. For DDR, statistically significant within-group and between-group improvement in all three measures (HI, VAS, APM) was seen for the hyaluronate group compared to the saline group throughout the 6-month test period. At the month-2 and month-3 examination intervals, twice as many patients treated with hyaluronate (90%) showed improvement compared to patients given placebo. Further, only 3% of patients with DDR who were treated with hyaluronate relapsed compared with 31% of patients with DDR given placebo. PMID- 8445464 TI - A double-blind study of topically applied 5% amlexanox in the treatment of aphthous ulcers. AB - A double-blind trial of amlexanox (C16H14N2O4) was carried out in 32 patients with recurrent oral aphthous ulcerations. During the treatment period, which lasted for 3 days, patients received either placebo topical paste or 5% amlexanox paste. The paste was applied by the investigator twice per day for 3 days and once on the fourth day. Efficacy was assessed by the following parameters: 1) pain measured by the patients marking a 15-cm line between poles connoting no pain versus severe pain; 2) erythema evaluated by the investigator on a four point scale ranging from none to strong; 3) size determined by investigator measurement of the perpendicular dimensions of the ulcer; and 4) an investigator's improvement scale consisting of six rank-ordered points from -1 for worsening of the ulcer with respect to previously described criteria to +4 when the ulcer had healed completely. All evaluations were based on a comparison with the day 1 visit of the patient. Outcomes for patients receiving the active ingredient were superior on all four criteria of effectiveness. Group differences for all criteria but pain reduction were statistically significant (P < .05). No side effects were reported. It was concluded that amlexanox is effective in reducing aphthous ulcer erythema, pain, and lesional size. PMID- 8445465 TI - Treatment of mandibular angle fractures using the AO reconstruction plate. AB - Fifty-two patients with fracture of the mandibular angle were treated by extraoral open reduction and internal fixation using the AO reconstruction bone plate (Synthes, Paoli, PA). None were placed into postsurgical maxillomandibular fixation. Four patients developed early infections requiring incision and drainage (7.5%). One patient required removal of the hardware after the fracture had healed. The use of the AO reconstruction bone plate for fractures of the mandibular angle was found to be very predictable and was associated with a low rate of complications. PMID- 8445466 TI - Auricular cartilage grafting after discectomy of the temporomandibular joint. AB - A consensus does not exist regarding an optimal reconstructive strategy following discectomy of the temporomandibular joint. This study presents retrospective documentation of the treatment outcome experienced with the use of autologous auricular cartilage grafting after discectomy in 26 joints. At an average follow up slightly in excess of 2 years, this procedure appears to have approximately 85% effectiveness in producing significant relief of pain and increasing mandibular range of motion. PMID- 8445467 TI - Double-gloving and the incidence of perforations during specific oral and maxillofacial surgical procedures. AB - The concerns of surgeons about effective means of barrier protection during surgery is increasing owing to concern about the human immunodeficiency virus (HIV). There are various oral and maxillofacial surgical procedures that require the use of sharp instruments, and the oral and maxillofacial surgeon may be at risk for contamination due to possible perforation of the surgical gloves when manipulating these instruments. This study evaluated the incidence of perforations when performing specific oral and maxillofacial surgical procedures when double-gloving barrier protection was used. It found an increased incidence of perforations when performing procedures that required the use of sharp instruments in comparison with those procedures that did not require the use of such instruments. PMID- 8445468 TI - Treatment of toxic epidermal necrolysis and Stevens-Johnson syndrome in children. AB - A retrospective study was carried out on eight consecutively treated children, 2 to 14 years of age, seven with toxic epidermal necrolysis and one with transitional-type Stevens-Johnson syndrome. The body surfaces affected ranged from 40% to 100%. Seven of the patients were taking a sulfonamide or anticonvulsant before the onset of their disease. Complete reepithelialization took an average of 15 days, but newly evolving lesions of the lips and oropharynx continued for approximately 4 more weeks. These lesions took an additional 2 to 4 weeks to heal. Only one of the children died. PMID- 8445469 TI - The use of liquid nitrogen cryotherapy in the management of locally aggressive bone lesions. AB - Cryosurgery has a unique role in the management of locally aggressive osseous lesions. By using a combination of enucleation and cryosurgery to devitalize the surrounding bone, the need for segmental mandibular resection is decreased. This article reviews 37 cases managed successfully in this manner. PMID- 8445470 TI - Complications associated with rigid internal fixation of facial bone fractures. AB - Rigid internal fixation is now a common method for treating fractures of the facial skeleton. However, it is a very precise technique that requires more time than intraosseous wiring. This article reports the complications associated with rigid internal fixation of facial fractures in 223 patients and compares the findings with those accompanying intraosseous wiring. PMID- 8445471 TI - Flow cytometric analysis of posterior oropharyngeal tumors. AB - To date, few studies have evaluated the diagnostic and prognostic potential of flow cytometry in oropharyngeal tumors. The purpose of this study was to evaluate the interrelationship of anatomic location with the cytogenetic and cytokinetic characteristics of squamous cell carcinomas of the posterior oropharynx. Forty eight paraffin-embedded squamous cell carcinoma specimens from the posterior oropharynx in clinical stages I to IV were analyzed with an Epics-C flow cytometer (Coulter Diagnostics, Hialeah, FL). Histopathologic grading was performed by the same pathologist, based on tumor differentiation. Of the 38 specimens suitable for analysis, several correlations were noted. First, as the %S-phase increased, the clinical stage increased. Second, as the histologic grade increased, the aneuploid frequency increased. Finally, as the tumor size increased, the histologic grade increased. From the results of this study, it was concluded that %S-phase may be useful in assessing the prognosis of squamous cell carcinomas of the posterior oropharynx. DNA index or aneuploid frequency, also may have value as a prognostic indicator. Finally, the lack of correlation between TNM staging and histologic grading stems not from tumor size but from nodal and metastatic involvement. Further studies are warranted to better define the usefulness of flow cytometric analysis in squamous cell carcinomas of the oropharyngeal region. PMID- 8445472 TI - Management of closed head injury in the patient with maxillofacial trauma. AB - Closed head injury (CHI) affects approximately one in five patients who sustain facial fractures. The effects can range from simple loss of consciousness to coma and death. The high incidence of CHI in the facial trauma population and the potential for mortality and neurologic morbidity make it a distinct concern of the practicing oral and maxillofacial surgeon. This article discusses the evaluation, monitoring, and management of CHI and includes special consideration of the treatment of maxillofacial injuries in these patients. PMID- 8445473 TI - Swelling of the retromolar region and cheek associated with limited opening. PMID- 8445474 TI - Adenomatoid hyperplasia of the palate. PMID- 8445475 TI - Chondrosarcoma arising in the temporomandibular joint: a case report and literature review. PMID- 8445476 TI - Postobstructive pulmonary edema as a sequela of temporomandibular joint arthroscopy: a case report. PMID- 8445477 TI - The aggressive odontogenic fibroma: report of a case. PMID- 8445478 TI - Multiple peripheral odontogenic fibroma, World Health Organization type, and central giant cell granuloma: a case report of an unusual association. PMID- 8445479 TI - Bilateral parotid sialadenopathy associated with general anesthesia: a case report. PMID- 8445480 TI - Surgical refinement of the anterior maxillary subapical osteotomy. PMID- 8445481 TI - Proper use of the holmium:YAG laser. PMID- 8445482 TI - Making the diagnosis clear. PMID- 8445483 TI - In situ PCR. PMID- 8445484 TI - Intimate relations: the serial endosymbiotic theory of the origin of eukaryotes. PMID- 8445485 TI - Growth factors: regulation of normal and neoplastic growth. AB - This paper presents an overview of current trends in growth factor research. The first part of the review considers the current classification of growth factors and their receptors. A model of cell proliferation regulation by growth factors is then presented. The final section reviews the latest concepts of the involvement of growth factors in the development of neoplasia. PMID- 8445486 TI - Ultrastructural features of fetal erythroid precursors infected with parvovirus B19 in vitro: evidence of cell death by apoptosis. AB - Human parvovirus B19 cannot be cultured in standard cell lines and relatively little is known about the intracellular life-cycle of the virus. In this study, ultrastructural features of B19 infection were examined using haemopoietic cell suspension cultures derived from human fetal liver. Erythroblasts from infected cultures frequently contained crystalline arrays of both full and empty virus like particles. The number and size of these arrays increased with the duration of culture, and their location changed from exclusively nuclear at 24 h post infection to both nuclear and cytoplasmic at 3 days post-infection. Arrays were occasionally found in cytoplasmic protuberances which appeared to be pinching off from the cell. The location of the arrays corresponded to the distribution of viral capsid protein determined by immunolabelling at the light microscope level. Cells containing viral crystalline arrays also exhibited nucleolar degeneration, extreme margination of the nuclear heterochromatin, and cytoplasmic vacuolation. These features are typical of cells undergoing individual programmed cell death or 'apoptosis'. The triggering of apoptosis in erythroid precursors by parvovirus B19 may help to explain the apparent lack of a strong inflammatory response to fetal B19 infection and may have implications for understanding the mechanisms of viral spread throughout the host. PMID- 8445487 TI - Proliferation and differentiation of tumour cells from B-cell lymphoma of mucosa associated lymphoid tissue in vitro. AB - Several characteristics of lymphomas of mucosa-associated lymphoid tissue (MALT type) suggest that they are antigen-dependent and that their growth parodies a normal immune response. We have previously shown that three cases of low-grade B cell MALT-type lymphoma recognize autoantigens. In this study, we investigated the response of three low-grade and one high-grade case of MALT-type lymphoma to anti-idiotypic antibody as a model of antigen binding either alone or as a co stimulus with B-cell mitogens. We also studied the response of tumour cells to interleukin-6 (IL-6), which induces differentiation to immunoglobulin-producing cells in many systems. Of the four cases studied, one low-grade case showed markedly enhanced proliferation in response to anti-idiotype alone. This could not be increased by the addition of mitogens. In the remaining two low-grade cases, mitogen responsiveness was observed which was affected by anti-idiotype either by an enhancement or by a reduction in the proliferative response. The high-grade case failed to respond to the stimuli studied. No response to IL-6 was observed. This study supports the suggestion that antigen may affect the pathogenesis of low-grade tumours of MALT type. PMID- 8445488 TI - Bronchus-associated lymphoid tissue (BALT) in human fetal and infant lung. AB - Bronchus-associated lymphoid tissue (BALT) has been defined as the organized lymphoid tissue of the lung. Although well described in a variety of animal species, documentation of its presence and development in human lung is limited. Because the tissue to volume ratio in adult lungs is so low, a systematic search for BALT would involve so many sections as to be impractical. In this study, therefore, we have studied post-mortem specimens of fetal (n = 102) and infant (n = 17) lungs, which have a much higher tissue to volume ratio. Fetal death was due to various causes but all but two infants died from sudden infant death syndrome. In the fetal lungs, the presence of BALT was almost invariably associated with chorioamnionitis or intrauterine pneumonia, being present in 24 of 51 of these cases (47 per cent). The earliest ill-defined lymphoid aggregate was seen at 16 weeks' gestation, while lymphoepithelium, a hallmark of mucosa-associated lymphoid tissue, could be identified at 20 weeks. In 51 fetuses without infection, BALT was found in only five cases (10 per cent). BALT was identified in 13/17 (77 per cent) of infant lungs and well-developed lymphoepithelium was evident in four cases. This study shows that BALT may be present in the human fetal and infant lung, but that its appearance is probably dependent on antigenic stimulation. PMID- 8445489 TI - Integrin expression in normal, hyperplastic, dysplastic, and malignant oral epithelium. AB - We have examined the distribution of a range of integrin subunits in normal and lesional oral mucosa. The alpha 2, alpha 3, alpha 6, beta 1, and beta 4 subunits were highly expressed in normal epithelium, and there was weaker, more variable expression of alpha 5 and alpha v. Expression of all subunits was highest in the basal layer of normal epithelium, but extensive staining above the basal layer was also observed, particularly in the floor of the mouth and the lateral margin of the tongue. In dysplastic lesions and hyperplastic epithelium adjacent to ulcers, suprabasal staining was even more pronounced. Staining patterns in squamous cell carcinomas showed considerable variation, both within and between individual tumours: in some areas there was staining reminiscent of normal epithelium, but uniform staining throughout tumour islands, and patchy and variable cytoplasmic and pericellular staining were also seen. Thirteen out of 17 carcinomas showed some loss of integrin expression: six out of ten moderately well differentiated tumours and all the poorly differentiated tumours. Focal loss of alpha 6 and beta 4 was most commonly observed, but loss of alpha 2 and alpha 3 also occurred. Since integrins regulate not only keratinocyte adhesion, but also the initiation of terminal differentiation, the changes in integrin expression that we have observed may have significance for the behaviour of individual tumours. PMID- 8445490 TI - AgNOR counts have no prognostic value in breast cancer. AB - The prognostic significance of silver-stained nucleolar organizer regions (AgNORs) was retrospectively studied among 230 patients with operable invasive breast cancer from a defined urban population. The number of AgNORs was evaluated from routinely processed paraffin sections by light microscopy at a total magnification of x630. The number of AgNORs had no predictive value on the 8-year survival rate corrected for intercurrent deaths (P = 0.2). A high number of AgNORs (> 2.7, the median value) was not related to any other prognostic variable studied except a low S-phase fraction measured by flow cytometry. AgNOR counting does not appear to be a useful prognostic variable in breast cancer. PMID- 8445491 TI - Differentiation-associated changes in mucin glycoprotein antigenicity in mucosa adjacent to rare gastrointestinal tract tumours of non-mucosal origin. AB - We have investigated changes in mucin antigenicity and morphology in the perineoplastic mucosa adjacent to rare, predominantly non-mucosal gastrointestinal (GI) tumours. Twenty-nine tumours of small and large intestine, including primary mesenchymal and ectodermal tumours, were examined immunohistochemically using 11 monoclonal antibodies (MAbs) raised against SIMA and LIMA (small and large intestinal mucin antigens). Non-epithelial GI tumours were essentially non-reactive, while adjacent mucosa showed altered mucin expression and morphology, in particular, features of transitional mucosa (TM). Combinations of different SIMA epitopes were detected adjacent to all colorectal tumours, and, similarly, LIMA epitopes adjacent to small intestinal tumours. Specific patterns adjacent to certain tumours may reflect influences of factors produced by individual tumours on mucin composition. Altered antigenicity and morphology in TM thus appear to be reactive changes in response to a wide range of GI tumours, presumably as a consequence of factors secreted by the tumour and/or a host response to the tumour. PMID- 8445492 TI - Early increase precedes a depletion of VIP and PGP-9.5 in the skin of insulin dependent diabetics--correlation between quantitative immunohistochemistry and clinical assessment of peripheral neuropathy. AB - Diabetic neuropathy affects both sensory and autonomic peripheral nerve fibres. Vasoactive intestinal polypeptide (VIP) is present in autonomic fibres which modulate sweat secretion, while calcitonin gene-related peptide (CGRP) is localized to cutaneous sensory fibres. In this study, immunohistochemistry and image analysis were used to assess changes of VIP and CGRP, and of the pan neuronal marker protein gene-product (PGP)-9.5, in skin biopsies of 18 patients affected by type 1 diabetes (age range 18-46 years) and from seven aged-matched controls. Patients were divided into three groups: group 1 (n = 6), with diabetes for 6 months to 3 years; group 2 (n = 5), with the disease for 5-10 years; and group 3 (n = 7), with diabetes for more than 10 years. VIP immunoreactivity (IR) and PGP-9.5-IR were significantly reduced around sweat glands (P < 0.005) in groups 2 and 3. Epidermal CGRP-IR and PGP-9.5-IR were significantly reduced in group 3 (P < 0.05). Twenty-eight per cent (5/18) of all patients showed high VIP IR around sweat glands (> 95 per cent confidence limits of controls) and all of these patients had diabetes for less than 3 years. Conversely, 55 per cent (10/18) of patients had low VIP-IR (< 5 per cent confidence limit of controls). The latter, compared with the former, showed a significantly longer duration of diabetes (Fisher exact test P = 0.002), presence of clinical autonomic neuropathy (Fisher exact test P = 0.04), and a reduced sural nerve conduction velocity (Fisher exact test P = 0.04). These results suggest that quantitative immunohistochemical analysis of peptide-containing cutaneous nerves allows an objective evaluation of nerve fibre alterations at early stages of diabetes than is currently possible with neurophysiological functional tests. PMID- 8445493 TI - Loss of LDH activity during membrane filtration. AB - Membrane filters rendered hydrophilic and composed of biphenyl polycarbonate, polyvinylidene fluoride (PVDF), acrylic copolymer, polysulfone, and mixed esters of cellulose were evaluated to determine which type of filter best can be used for the filtration of lactate dehydrogenase (LDH) solution. Also, the effect of the membrane pore size was evaluated. LDH solution was passed through the filters at a controlled flow rate, after which the filtrate was assayed for LDH activity and protein content using the Bradford method. Polycarbonate and PVDF filters generally showed low loss of protein, except 5 microns PVDF filters. Mixed esters of cellulose, acrylic copolymer, and polysulfone caused considerable loss of protein during passage of the LDH solution through the filter. Interestingly, it was also found that, generally, as the pore size increased the amount of protein loss decreased. However, 5 microns PVDF and mixed esters of cellulose filters showed more loss than their corresponding 0.65 microns and 3 microns pore size filters, respectively. In all cases, more protein was recovered in the filtrate fractions as the volume of LDH solution filtered was increased, suggesting that the mechanism of loss is adsorption and that the magnitude of loss is related to saturation of the matrix polymer surfaces. PMID- 8445494 TI - Validation--mission completed? PMID- 8445495 TI - Evaluation of closure integrity after multiple penetrations. AB - The purpose of this investigation was to simulate in-use testing of closures to determine how many doses could be reasonably withdrawn from a multiple dose vial of a product without compromising the integrity of the closure. Four types of studies were done: 1) a simulated in-use test, 2) a coring test development study, 3) effect of sterilization on coring, and 4) exploratory studies of closure leakage after multiple penetrations. A modified drill press was used for the studies. West 1888 and West 1535 closures were evaluated by the simulated in use test using a 26G Needle. The results indicated that few particles were generated after 20 penetrations of both closures. There was a marked increase in particles after 30 penetrations. When sterilized closures were tested, it was found that West 1888 generated no particles after 10 insertions with 21G and 18G needles, but there was an increase in the number of particles after 20 insertions. With West 1535, particles were generated after only 10 insertions. Interestingly, autoclaved closures released fewer particles than closures that were not autoclaved. Leakage was observed only from West 850 closures and only under relatively high pressure differential conditions. PMID- 8445496 TI - Validation of environmental monitoring methods and levels. AB - Environmental monitoring is an essential requirement in the pharmaceutical industry. Results which the manufacturer obtains from environmental monitoring must be reproducible and assure that the aseptic environment is under control. Today, more than ever, environmental data is scrutinized during FDA CGMP and preapproval NDA inspections and this trend will likely continue. Environmental test methods which have been in existence for years are accepted throughout the industry, but the user must bear the responsibility of proving that the methods yield reproducible results. New test methodologies must be validated to be as good as or better than the methods they are replacing. Currently, environmental result alert/action levels in existing facilities should be based on industry guidelines and facility performance validation. The pharmaceutical manufacturer must demonstrate that the levels which have been established for the facility have a statistical basis related to the historical performance of the facility. As time goes on, environmental levels may be readjusted to coincide with the operational performance levels of the facility. PMID- 8445497 TI - Vacuum measurement in steam sterilizable lyophilizers. AB - This paper discusses the performance and sterilizability attributes of several different types of capacitance manometers as used in steam sterilizable lyophilizers. Recommendations are made for proper capacitance manometer selection, installation, operation, and calibration. An overview of vacuum gauging methods and the performance and sterility benefits of a new high temperature (125 degrees C)/high-overpressure capacitance manometer are discussed. PMID- 8445498 TI - Chemical compatibility of cefmetazole sodium with ranitidine hydrochloride during simulated Y-site administration. AB - The stability of cefmetazole sodium and ranitidine hydrochloride was studied under conditions simulating administration via a Y-injection site into a primary infusion line. Cefmetazole sodium was reconstituted with both 0.9% sodium chloride injection (50 mL or 100 mL) and 5% dextrose injection (50 mL) to produce premixing concentrations of cefmetazole 10 and 20 mg/mL. Ranitidine hydrochloride injection was diluted with 50 mL 0.9% sodium chloride injection to give premixing concentrations of ranitidine 1 mg/mL. To simulate Y-site administration, 2 mL of cefmetazole was mixed with 2 mL of ranitidine in a 10-mL glass test tube. All study mixtures were prepared in triplicate and stored at room temperature (22-23 degrees C) under normal fluorescent room lighting. Samples of these admixtures were inspected for visual changes and tested for pH. The concentrations of two drugs were immediately determined by stability-indicating high-performance liquid chromatographic assay methods after mixing and at 1, 2, and 4 hours. No visual changes were observed. The pH in the admixtures was influenced by concentrations of the two drugs. The pH of each single-drug solution did not change during the study period. On the other hand, the pH of any admixtures of cefmetazole and ranitidine solutions prepared with 0.9% sodium chloride or 5% dextrose injection, decreased. Cefmetazole in any of the admixtures with ranitidine retained greater than 95% of its original concentration for 4 hours.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8445499 TI - PDA response. FDA advance notice of proposed rulemaking on electronic identification/signatures. Parenteral Drug Association. PMID- 8445500 TI - Studies in phlebitis. IV: Injection rate and amiodarone-induced phlebitis. AB - Using a rabbit ear model and techniques developed previously (1) the relationship between injection rate and injection phlebitis is investigated for amiodarone HCl and its vehicle. A number of injection rates ranging from 0.02 to 3.0 ml/min are studied using this model. Thermal measurements and visual evaluations are used for phlebitis quantitation. The severity of phlebitis is found to be dependent upon the injection rate for amiodarone HCl while the vehicle did not produce phlebitis at any rate. Strong correlations between the thermal measurements and visual evaluations are found for both amiodarone HCl and its vehicle. PMID- 8445501 TI - Studies in phlebitis. V: Hemolysis as a model for phlebitis. PMID- 8445502 TI - Validation and control of non-standard sterilization processes. Committee on Microbial Purity. FIP (International Pharmaceutical Federation). AB - With the upcoming abundance of sterilization techniques applied to various pharmaceutical product types, it has appeared useful to the committee to compile general guidelines for the proper mastery of this critical step of many pharmaceutical processes. Derived from the experience gained with conventional and more recent sterilization processes, this reports offers guidance for the definition of product sterility and the validation and control of the safety, reliability, efficiency, and proper operation of the non-standard sterilization processes. PMID- 8445503 TI - Influence of polybutylcyanoacrylate nanoparticles and liposomes on the efficacy and toxicity of the anticancer drug mitoxantrone in murine tumour models. AB - Polybutylcyanoacrylate (PBCA) nanoparticles were prepared and loaded with mitoxantrone, a highly effective anticancer drug. The proportion of mitoxantrone bound to the particles was analysed to be about 15 per cent of the initial drug concentration with the incorporation method and about 8 per cent with the adsorption method. Selected nanoparticle formulations were tested in leukaemia- or melanoma-bearing mice after intravenous injection. Efficacy and toxicity of mitoxantrone nanoparticles were compared with a drug solution and with a mitoxantrone-liposome formulation (small unilamellar vesicles with a negative surface charge). Furthermore, influence of an additional coating surfactant, poloxamine 1508, which has been shown to change body distribution of other polymeric nanoparticles, was investigated. It was shown that PBCA nanoparticles and liposomes influenced the efficacy of mitoxantrone in cancer therapy differently: liposomes prolonged survival time in P388 leukaemia, whereas nanoparticles led to a significant tumour volume reduction at the B16 melanoma. Neither nanoparticles nor liposomes were able to reduce the toxic side-effects caused by mitoxantrone, namely leucocytopenia. A slight additional influence of the coating surfactant was observed with only one preparation. PMID- 8445504 TI - Citric acid as a plasticizer for spray-dried microcapsules. AB - An aqueous spray-drying process was used to coat theophylline particles with a cellulose polymer, sodium carboxymethylcellulose (NaCMC) or hydroxypropylmethylcellulose (HPMC). Effect of a plasticizer, citric acid, was studied. Strength of cast films have a direct relationship to the dissolution T50% values of the respective spray-dried products. With varying plasticizer concentrations, changes in interaction between plasticizer and polymer, and in size of crystallized drug crystals, were observed with HPMC films. The plasticizer content also affected the films of NaCMC by bringing about a change in the form and arrangement of the drug. X-ray diffraction analyses of the different spray-dried products revealed a possibility of the predominance of different crystal forms. Spherical spray-dried microcapsules of NaCMC were formed with a 20-30% w/w plasticizer content. With HPMC, as plasticizer concentration was increased there was a corresponding increase in mean size of the spray-dried products. In terms of drug release and formation of spherical particles, a plasticizer concentration of 30% w/w was found to be suitable for both HPMC and NaCMC. PMID- 8445505 TI - One continuous process of agglomeration and microencapsulation for enoxacin. Preparation method and mechanism of microencapsulation. AB - A novel microencapsulation method was developed by using the wet spherical agglomeration (WSA) technique. Spherical agglomerates containing enoxacin (ENX) or lactose were prepared in the acetone-n-hexane-ammonia water (or distilled water) solvent system, and were microencapsulated continuously with the aminoalkylmethacrylate copolymer (Eudragit RS). Microencapsulation was performed with a modified organic phase separation by the non-solvent addition method. By selecting proper composition ratio of acetone and n-hexane, the WSA solvent system turned to a non-solvent for a wall material, i.e. Eudragit RS. Dichloromethane was used as a good solvent because it did not affect the characteristics of spherical agglomerates prepared in the WSA system. With this technique the Eudragit RS coacervate droplets were firstly generated in the solvent composed of a higher acetone volume ratio in the acetone/n-hexane mixture, and continuously the coacervate droplets were deposited efficiently onto the agglomerates by adding additional n-hexane into the system. Spherical microcapsules with the size ranged between 100 and 1000 microns, were successfully produced owing to the spherical shape of agglomerates containing ENX or lactose. PMID- 8445506 TI - Liposomal drug delivery to the eye and lungs: a preliminary electron microscopy study. AB - Colloidal gold was used as an electron-dense marker for multilamellar vesicles to study the mechanism of liposome drug delivery to the eye and lung. A gold labelled multilamellar vesicle could be seen in the conjunctiva but there was no evidence of vesicles adsorbed to the epithelial surface of cornea or conjunctiva. In the lung, a free gold particle was isolated in type 1 epithelial cells and many vesicular structures were observed in the alveolar spaces which were not gold labelled. Experiments performed so far indicate that adsorption and not endocytosis was the major mechanism of uptake of drug or marker for multilamellar vesicles except for conjunctiva. PMID- 8445507 TI - Influence of total surface area of core material on yield of deposited coacervate. AB - Influence of total surface area of core material on yield of deposited coacervate was evaluated. A simple coacervation method was employed solvent-evaporation method were used as a model core substance. A mixed polymer system--aqueous solution of gelatin and potassium salt of cellulose acetate phthalate--was used as a wall material. A sodium sulphate solution acted as a desolvating agent. Results obtained clearly show an opposite effect of the size of core material and derived total surface area on the yield of attached coacervate. While keeping the amount of core material constant, the amount of deposited coacervate increased both with the decreased size of core particles (increased total surface area), and increased concentration of desolvating agent. The proportion of wall material gradually increases with the increased concentration of sodium sulphate solution in the range from 1 to 9 per cent of the weight of microcapsules. Analysis of variance was used for the evaluation of obtained data. PMID- 8445508 TI - Analysis of release data in the evaluation of the physical state of progesterone in matrix systems. AB - Ethylene-vinyl acetate microspheres were prepared by an emulsion solvent evaporation method as sustained delivery carriers of progesterone. Physical state of the drug in the microspheres was affected by drug loading level. As thermal analysis and mathematical release models showed, low payloads of the matrix supported the molecularly dispersed drug. Crystalline drug appeared only as the drug loading level increased. The release process of the crystalline drug produced a porosity increase in the polymeric system; thus, the drug could diffuse through pores and channels. Hence, the porosity of the matrix structure was affected by the payload. This hypothesis could justify the increasing goodness-of-fit of the release data to the square-root model as the drug loading level of the microspheres increased. PMID- 8445509 TI - Disposition of liposomal gentamicin following intrabronchial administration in rabbits. AB - Use of liposomes as carriers of gentamicin for intrabronchial pulmonary delivery was investigated in rabbits. Gentamicin, in isotonic glutamic acid buffer, pH 4.5, was encapsulated in multilamellar vesicles (MLVs) and administered intrabronchially. Higher drug concentrations were found at the pulmonary site of liposome instillation for 1 day as compared with free unencapsulated antibiotic. When time-course distributions of gentamicin given in the liposomal or free form were measured in bronchoalveolar lavages (BAL), similar accumulations were observed up to 4 h, but the drug remained longer (24 h) after administration of the liposomal formulation. Higher amounts of antibiotic were detected in BAL supernatant 1 h after instillation of plain gentamicin; this difference stopped being significant after 4 h. A microbiological assay outlined the bacteriostatic activity of gentamicin released from MLVs and recovered in BAL supernatant. Liposomal gentamicin accumulated in the BAL cell pellet 1 h after intrabronchial instillation; it decreased progressively but minute amounts were still detected after 1 day. On the contrary, no gentamicin was found in the pellet at any time after free drug administration. Comparison of aminoglycoside concentrations in plasma and kidneys indicated lower and constant levels when the liposomal form was instilled. Liposome encapsulation altered the disposition of gentamicin in a way suggesting improved pulmonary concentration and lower systemic toxicity. PMID- 8445510 TI - Formulation and evaluation of vinylpyrrolidone/vinylacetate copolymer microspheres with griseofulvin. AB - Regular spherical microspheres of 220-260 microns average size have been prepared from vinylpyrrolidone/vinylacetate copolymer using a solvent evaporation method. Griseofulvin has been incorporated into these microspheres and its physical characterization has been carried out by differential scanning calorimetry (DSC), X-ray diffractometry and X-ray photoelectron spectroscopy. An increase of solubility was observed only with the 1:3 drug/polymer microspheres and the comparison of the dissolution profiles of microspheres with pure griseofulvin resulted in an enhancing effect. Furthermore the release rate of griseofulvin, incorporated into the microspheres, was shown to be biphasic and dependent upon the penetration of water into the microspheres, hydration and dissolution of the polymer and finally dissolution of the drug. PMID- 8445511 TI - A few observations. PMID- 8445512 TI - The effects of diaper brands, urine volume, and time on specific gravity measurement. AB - Nurses use urine specific gravity to assess fluid volume status in pediatric patients. Specific gravity of five leading brands of disposable diapers was measured to determine the effects of diaper brand, urine volume, time elapsed, and method of specific gravity measurement comparing the two methods of refractometry and N-Multistix SG (Ames Division, Miles Inc., Elkhart, IN). Immediately after a baby voided 20 mL of urine into any disposable diaper, the specific gravity by refractometer accurately compared with the control standard. Measurement accuracy by N-Multistix SG was only assured if Pampers (Procter & Gamble, Cincinnati, OH) were used. However, both methods were inaccurate at 4 hours with 20 mL of urine. Immediately after a baby voided 40 mL of urine into any disposable diaper, both methods were accurate when compared with the control. At 4 hours, only Pampers and Chux (Procter & Gamble, Cincinnati, OH) were accurate by refractometry, and Pampers alone was accurate by N-Multistix SG. PMID- 8445513 TI - Content validation of standards of nursing care for the child with asthma. AB - Standards of nursing care for the child with asthma were developed utilizing outcome criteria to evaluate the patient's status. These standards were submitted to three experts in the field of pulmonary nursing to enable calculation of a content validity index (CVI). The experts also provided qualitative comments to improve clarity of the standards. The CVI for the standards was 0.85. The standards were revised to reflect the CVI and the qualitative comments by the three experts. PMID- 8445514 TI - Parent-nurse collaboration: using the caregiver identity emergence phases to assist parents of hospitalized children with disabilities. AB - Twenty-three parents of hospitalized or recently hospitalized children aged 2 to 13 years and with cognitive impairments and a variety of disabling conditions were recruited to participate in a qualitative study exploring parental caregiving experiences. A substantive theory, caregiving identity emergence, was generated from the data. An inadvertent, developmental identity emergence process and trajectory were described by the parents. The theory generated in this study proposes that parental caregiving characteristics are acquired systematically as parents incorporate new knowledge and alter their behaviors to manage caregiving responsibilities. The focus of this article is on how the characteristics of the parent caregiver described in the findings of the study provide basic background information about parental caregiving from which pediatric nurses can formulate facilitative interventions to create caregiving partnerships. PMID- 8445515 TI - Parental distress: caring for medically fragile children at home. AB - Home care (rather than hospital care) for a diverse group of medically fragile children has expanded in the last decade without an adequate understanding of its impact on families. In this report, the psychological distress of parents was measured using family data and a standardized psychological distress instrument. Of 57 families studied, 59% of the mothers and 67% of the fathers reported significant levels of distress symptoms. Regressions analysis suggest that factors associated with increased family responsibility contribute to parents' distress. The type and amount of professional support also affect parental distress. PMID- 8445516 TI - The impact of a diabetes education program on children and mothers. AB - To investigate the effect of a diabetes education program for school-age diabetic children and their mothers, an evaluative research approach was used in this exploratory study. Significant gains were made and maintained for 3 months for both the children and their mothers on most of the primary goals of the education program that focused on improving diabetes knowledge and skills. Recommendations are included for improving program effectiveness and research designs. PMID- 8445517 TI - Life transitions of parents at the unexpected death of a school-age and older child. AB - The purpose of this study was to describe parents' responses to the unexpected death of a school-age and older child. The nonrandomized sample consisted of 16 mothers and 11 fathers who each were interviewed at least 1 year after their child's death and who were not in active therapy for grief resolution at the time of their participation. Data were collected in single, tape-recorded, private interviews. Using Life Transition Theory as a framework (Selder [Schmitt], 1982), data were analyzed by systematic analytic induction. Study findings suggest there are no time lines for resolution of grief. Parents experience certain processes that recur over time. Processes identified and described are: presencing (the child), which is a way of experiencing memories of their child; reactivation, which is a process of re-experiencing the trauma of the death; and identification of missed options, which involves identifying those things the parent will never experience with their child, such as graduation, marriage, etc. PMID- 8445518 TI - Delegation: professional judgment or economic necessity? PMID- 8445519 TI - Product safety alert: syringe cap aspiration. PMID- 8445520 TI - Joining together: developing a clinical program for nursing faculty. PMID- 8445521 TI - Concepts of illness of school-age children in rural and urban Thailand. PMID- 8445522 TI - Current perspectives on the dissolution stability of solid oral dosage forms. AB - Dissolution stability (i.e., retention of the dissolution characteristics of a solid oral dosage form from the time of manufacture up to its expiration date) is a critical parameter from the standpoint of quality control, regulatory compliance, and impact on the bioavailability of the product. Significant changes in the in vitro release profiles of a drug product during storage may alter its bioavailability. Factors that affect the dissolution stability of a product during aging include formulation components (active drug, excipients, and coating materials), processing factors, storage conditions, and packaging. The role of each of these factors in promoting changes in dissolution in both immediate release and modified-release products is dependent on the product and has to be evaluated on a case-by-case basis. Although data obtained under accelerated conditions of storage are not useful in predicting the dissolution shelf-life of the product under ambient conditions, they are of value in assessing the "ruggedness" of the product and its ability to withstand the varied climatic conditions during transport, shipping, and storage. The clinical significance of alterations in the in vitro dissolution profiles that may occur during aging and strategies to avert and counteract such changes are discussed in the article. PMID- 8445523 TI - Iontophoretic transdermal delivery of salicylic acid and lidocaine to local subcutaneous structures. AB - The depth of penetration of solutes into underlying tissues after transdermal iontophoresis has been evaluated with salicylic acid and lidocaine as model compounds. Concentrations of salicylic acid and lidocaine were measured in plasma and tissues below the donor electrode after iontophoresis in rats. The concentrations obtained were then compared with those obtained after passive delivery (without iontophoresis) of the drugs applied either to intact epidermis or to the exposed dermis (epidermis removed) of rats. Iontophoresis yielded high concentrations of lidocaine in each underlying tissue when compared with passive application to rat epidermis or dermis. Negligible concentrations of lidocaine in plasma were found for each mode of delivery. Similar concentrations of salicylic acid were found in each of the underlying tissues after delivery of salicylic acid either by iontophoresis through intact epidermis or after passive application to the exposed dermis. Negligible concentrations of salicylic acid in underlying tissues were obtained after passive application to intact epidermis. The plasma salicylic acid concentrations observed after both iontophoretic epidermal and passive dermal (epidermis removed) treatments were approximately the same as the tissue salicylic acid concentrations observed at approximately 3 4 mm below the application site. It is concluded that transdermal iontophoresis allows salicylic acid and lidocaine to be effectively delivered across the stratum corneum. Local direct deep tissue penetration of lidocaine is facilitated by iontophoresis. The concentrations of salicylic acid in deeper underlying tissues (> 3-4 mm) tend to be similar to the concentrations in plasma after either iontophoresis or passive dermal application, a result indicating that direct penetration of salicylic acid occurs only to a depth of 3-4 mm. PMID- 8445524 TI - In vitro-in vivo correlation for modified-release formulations. AB - A correlation of in vitro dissolution rate measurements with in vivo pharmacokinetic results in a human study was obtained for a sustained-release formulation of bromocriptine. Different methods were applied to reach this correlation, and the various outcomes were compared. PMID- 8445525 TI - Logarithmic transformation in bioequivalence: application with two formulations of perphenazine. AB - The rationale for using the logarithmic transformation on concentration-dependent pharmacokinetic parameters a priori is presented. This rationale is based on theoretical pharmacokinetic and statistical grounds, but is also applicable to the practice of physicians in dealing with variations of drug treatment within and between patients. The implications of the transformation on data analysis, specifically analysis of variance, and estimation and inference from the analysis as it pertains to bioequivalence decisions are explored. Implementation of the transformation is shown, with an example of two perphenazine formulations in a single-dose crossover study. It is concluded that the transformation has to be accepted on theoretical grounds because sample sizes are too small in bioequivalence studies and too susceptible to extreme values to state with any certainty the actual distribution of pharmacokinetic parameters or their differences within a subject. PMID- 8445526 TI - Transplacental and nonplacental clearances of diphenhydramine in the chronically instrumented pregnant sheep. AB - Pharmacokinetic studies of the histamine H1-receptor antagonist diphenhydramine were conducted in eight chronically instrumented pregnant sheep at 126-138 days of gestation. Diphenhydramine was administered by simultaneous intravenous bolus injection and infusion to steady state given 48 h apart, to the ewe and the fetus on separate occasions. Average steady-state drug concentration in plasma after maternal infusion was 212.1 +/- 67.8 ng/mL in the mother and 36.3 +/- 14.4 ng/mL in the fetus, resulting in a fetal-to-maternal concentration ratio of 0.19 +/- 0.10. Following fetal infusions, maternal and fetal steady-state drug concentrations were 31.1 +/- 11.6 and 447.6 +/- 185.2 ng/mL, respectively. The free fraction of diphenhydramine determined in the fetus (0.277 +/- 0.087) was significantly greater than that in the mother (0.141 +/- 0.079). Transplacental and nonplacental clearances were calculated at steady state according to a general two-compartment open model, with drug elimination occurring from both compartments. The total fetal clearance (472.7 +/- 215.7 mL/min) was relatively small compared with the total maternal clearance (3426.1 +/- 905.8 mL/min). The transplacental clearance from fetus to mother (264.4 +/- 138.7 mL/min) was approximately threefold higher than that from mother to fetus (82.4 +/- 40.5 mL/min). Maternal nonplacental clearance (3343.8 +/- 890.7 mL/min) accounted for 97.8 +/- 1.1% of the maternal total clearance, whereas fetal nonplacental clearance (208.4 +/- 80.4 mL/min) accounted for 45.1 +/- 4.7% of the fetal total clearance. It is concluded that in the fetus both the transplacental and nonplacental pathways are important for drug elimination. PMID- 8445527 TI - Metabolism of 3-indolylacetic acid during percutaneous absorption in human skin. AB - This study assessed the in vitro percutaneous absorption and metabolism of 3 indolylacetic acid after topical dosing to human skin from four sources. The metabolism of the compound during percutaneous absorption was assessed. The absorbed and metabolized chemicals were analyzed by radioactive scintillation counting and thin-layer chromatography: 1.2% +/- 0.04%, 1.4% +/- 0.07%, 3.0% +/- 1.0%, and 0.1% +/- 0.02% of the applied doses permeated through human skin samples from sources A to D, respectively, whereas 3.4% +/- 0.5% to 20.0% +/- 0.2% of the applied doses were retained by the skin. Of the absorbed dose, 2.1% +/- 1.0% to 12.1% +/- 3.5% was present as metabolites in the receptor fluid, and 2.2% +/- 0.5% to 5.2% +/- 0.1% was present as metabolites retained in the skin. Microsomal fractions were prepared from the skin samples, and the actions of these preparations on 3-indolylacetic acid were estimated. 5'-Hydroxyl-3 indolylacetic acid, 5',6'-dihydroxy-3-indolylacetic acid, and 5,6-dihydroxyindole were formed both during percutaneous absorption and by skin microsomal preparations. In addition, the skin samples biotransformed the acid to metabolic indican (3-indoxylsulfuric acid) and to the glucuronide conjugate of indole. The possible functional significance of the metabolism is discussed. PMID- 8445528 TI - Hydrophobicity parameter of diazines. III: Relationship of partition coefficients of monosubstituted diazines and pyridines in different partitioning systems. AB - The logarithm of the 1-octanol-water partition coefficient value (log Poct) was compared with those from CHCl3-water (log PCL) and di-n-butyl ether-water (log PE) for (di)azines substituted singly by nonhydrogen-bonding and hydrogen accepting substituents (2-substituted pyrazines, 2-substituted pyrimidines, 5 substituted pyrimidines, and 2-substituted pyridines). The difference between log Poct and log PCL for diazines was primarily governed by the number of hydrogen bonding sites in the substituent. For 2-substituted pyridines, the difference in the hydrogen-bonding association of the ring N-atom with octanol from that with CHCl3 was also significant. In the relationship between log Poct and log PE, the hydrogen-bonding solvations of the ring N-atom(s), as well as the hydrogen accepting substituent with octanol, should be taken into account because the butyl ether acts as a nonhydrogen-bonding solvent. PMID- 8445530 TI - Survival of Staphylococcus aureus in oral administration liquid medicaments and influence of count medium on survival. AB - The survival of Staphylococcus aureus was studied in 30 oral administration liquid medicaments (15 syrups and 15 solutions) to determine the effectiveness of the preservatives, the influence of the culture medium used in the enumeration of the surviving microorganisms, and the loss of the enzyme coagulase, phosphatase, DNase (deoxyribonuclease), and thermonuclease. Samples were inoculated with 6.3 6.5 x 10(5) viable cells per milliliter and were stored at room temperature for 60 days. Aliquots were taken for analysis at 0, 15, 22, 30, and 60 days after samples were inoculated. The enumeration of S. aureus was made by most probable number method (MPN) with six liquid culture media: triptone soy (TS), TS with 10% NaCl (TSS), TS and TSS with 0.2% catalase, Mannitol salt, and Tellurite-mannitol glycine. The survival of S. aureus was lower in solutions than in syrups, decreased with the storage time, and depended on the culture medium utilized in the enumeration. Nonselective media were more sensitive than selective ones; that is, a better percentage of recovery was achieved with TS and the catalase medium. The preservative was effective in 93.3% of the samples. Coagulase was the most stable enzyme and phosphatase, DNase, and thermonuclease disappeared during the storage period. PMID- 8445529 TI - Substituted thiosemicarbazides and corresponding cyclized 1,3,4-oxadiazoles and their anti-inflammatory activity. AB - Several 1-(4-biphenoxyacetyl)-4-substituted arylthiosemicarbazides and their corresponding cyclized 2-(4-biphenoxymethyl)-5-arylamino-1,3,4- oxadiazoles were synthesized and characterized by elemental analyses and IR, mass, and nuclear magnetic resonance spectra. All compounds were evaluated for anti-inflammatory activity by determining their ability to provide protection against carrageenin induced edema in rat paw. The anti-inflammatory activity possessed by substituted thiosemicarbazides [100 mg/kg, intraperitoneal(ip)] ranged from 22 to 68%, whereas substituted 1,3,4-oxadiazoles (100 mg/kg, ip) provided protection of 10 76%. Hydrocortisone (10 mg/kg, ip) and oxyphenbutazone (40 mg/kg, ip), used as standard reference drugs, decreased edema in rat paw by 44.6 and 52.9%, respectively. All compounds (1 mM) possessed antiproteolytic activity that was reflected by their ability to cause in vitro inhibition of trypsin-induced hydrolysis of bovine serum albumin. This inhibition ranged between 43 and 72% for substituted thiosemicarbazides and 30 and 83% for substituted 1,3,4-oxadiazoles. PMID- 8445531 TI - Site of action for the inhibition by gold sodium thiomalate of rabbit platelet activation. AB - The inhibitory action of the gold-based drug gold sodium thiomalate was investigated in rabbit platelets. Gold sodium thiomalate at concentrations of 0.25-13 x 10(-4) M inhibits collagen-, ADP-, and 9,11,dideoxy-11 alpha,9 alpha epoxymethanoprostaglandin F2 alpha (U46619)-induced aggregation as well as collagen- and U46619-induced serotonin release. This inhibition occurs in both Tyrodes-albumin or Tyrodes-gelatin buffer systems. Preincubation of gold sodium thiomalate with platelets resulted in less inhibition as the time of preincubation increased. The inhibitory effect of gold sodium thiomalate could be removed by washing the platelets. Other sulfhydryl-reacting compounds, such as D penicillamine, thiomalic acid, 5,5'-dithiobis-2-nitrobenzoic acid, and 6,6' dithiodinicotinic acid, were all capable of inhibiting collagen-induced aggregation and serotonin release. Evidence is presented that gold sodium thiomalate interferes with the activation of rabbit platelets by several activators, that this action of gold sodium thiomalate is similar to the action of other sulfhydryl-reacting agents, that this inhibition is likely occurring at the membrane, and that the action of the drug is not dependent on the presence of albumin. PMID- 8445532 TI - Rapid simultaneous determination of tryptophan and tyrosine in synthetic peptides by derivative spectroscopy. AB - A method for the simultaneous quantitative determination of tryptophan and tyrosine in synthetic peptides by second-order derivative diode-array spectroscopy is reported. The method does not require hydrolysis of the peptides or a derivatization reaction; the sample is dissolved in 0.1 N NaOH and directly scanned between 262 and 264 nm to detect tyrosine and between 304 and 306 nm to detect tryptophan. From these results the peptide content of the synthetic sample can be easily calculated in a very simple and fast way. The results obtained by the described method with several peptides are compared with those obtained by classical high-performance liquid chromatographic analysis of amino acids after peptide hydrolysis. A very good correlation was found both for the tryptophan/tyrosine molar ratio and the peptide content. PMID- 8445533 TI - pH-metric log P. II: Refinement of partition coefficients and ionization constants of multiprotic substances. AB - A generalized, weighted, nonlinear least squares procedure is developed, based on pH titration data, for the refinement of octanol-water partition coefficients (log P) and ionization constants (pKa) of multiprotic substances. Ion-pair partition reactions, self-association reactions forming oligomers, and formations of mixed-substance complexes can be treated with this procedure. The procedure allows for CO2 corrections in instances where the base titrant may have CO2 as an impurity. Optionally, the substance purity and the titrant strength may be treated as adjustable parameters. The partial differentiation in the Gauss-Newton refinement procedure is based on newly derived analytical expressions. The new procedure was experimentally demonstrated with benzoic acid, 1-benzylimidazole, (+/-)-propranolol, and mellitic acid (benzenehexacarboxylic acid, AH6). Ionic strength (l) was adjusted with KNO3. Benzoic acid (20 degrees C; l 0.1 M): pKa = 3.99 +/- 0.02, log P = 1.96 +/- 0.02, log P (anion) = -1.2; 1-benzylimidazole (25 degrees C; l 0.1 M): pKa = 6.70 +/- 0.03, log P = 1.60 +/- 0.04; propranolol (25 degrees C; l 0.1 M): pKa = 9.53 +/- 0.06, log P = 3.35 +/- 0.03, log P (cation) = 0.62 +/- 0.08; mellitic acid (26 degrees C; l 0.2 M): pKas 1.10 +/- 0.46, 1.69 +/ 0.03, 2.75 +/- 0.02, 4.00 +/- 0.02, 5.05 +/- 0.01, and 6.04 +/- 0.02; in the presence of 0.01 M n-Bu4NBr, log P (AH6) = 1.5, log P (AH5-) = 1.1, log P (AH4(2 )) = 0.8, log P (AH3(3-)) = 0.3, log P (AH2(4-)) = -0.1, and log P (AH5-) = -0.5 (all +/- 0.1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8445534 TI - Microencapsulation of drugs with aqueous colloidal polymer dispersions. AB - Sustained-release polymer particles containing drugs with various solubility characteristics (ibuprofen, theophylline, guaifenesin, and pseudoephedrine HCl) were prepared with colloidal polymer dispersions in a completely aqueous environment as an alternative to conventional microencapsulation techniques, which use organic solvents. Spherical particles were prepared by spraying or dropping dilute sodium alginate solutions (0.67%, w/w) containing the dissolved or dispersed drug and colloidal polymer particles into calcium chloride solutions. The gelled particles, which formed by ionotropic gelation of the polysaccharide with calcium ions, were dried and cured at 60 degrees C to cause fusion of the colloidal polymer particles into a homogeneous matrix system. Actual drug contents close to 50% and encapsulation efficiencies of between 80 and 98% were achieved with all drugs. Guaifenesin and ibuprofen acted as plasticizers for the ethyl cellulose pseudolatex, whereas with theophylline and pseudoephedrine HCl, dibutyl sebacate had to be added as a plasticizer to yield a nondisintegrating polymer matrix. The stirring time before separation of the particles from the gelation medium had to be minimized with the water-soluble drugs to maximize drug loading; however, it was not critical with the water insoluble drugs. Drug release was a function of the solubility of the drug, drug loading, and the type of polymer dispersion used. PMID- 8445535 TI - Preparation and evaluation of Eudragit gels. VI: In vivo evaluation of Eudispert rectal hydrogel and xerogel containing salicylamide. AB - Eudispert hv hydrogel and xerogel preparations containing salicylamide displayed sustained-release plasma profiles when compared with other conventional rectal preparations. The absolute bioavailability of salicylamide was 97.3% for the hydrogel preparation and 98.4% for the xerogel preparation. These results may arise because the gel preparation stays at the application site, the lower part of the rectum, over a fairly long period because of its bioadhesive force. Furthermore, the gastrointestinal and hepatic first-pass elimination of salicylamide can be avoided completely by rectal administration of these preparations. Visual and optical microscopic observation of rectal membranes indicated no irritation or abnormality after administration of Eudispert hv hydrogel and xerogel. PMID- 8445536 TI - Structure--anticancer and structure--genetic activity relationships of homo-aza steroidal esters of N,N-bis(2-chloroethyl)aminocinnamic acid isomers. AB - Four steroidal lactams of the A- and D-rings were used for the esterification in the C-3 or C-17 positions, respectively, of their nuclei with the N,N-bis(2 chloroethyl)aminocinnamic acid isomers. The condensation reaction of the hydroxylic group of the steroidal lactams with each mustard was effected in dichloromethane in the presence of the catalyst p-dimethylaminopyridine and dicyclohexylcarbodiimide as dehydrating agent. The esters were obtained in pure form after column chromatography, and their structures were verified and confirmed by analytical methods (IR and UV spectra). The 12 esters were tested in vivo against P388, L1210 leukemias, Ehrlich ascites tumor, and melanoma B16. The esters 3 alpha-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17- oic-13,17 lactam-o,m,p-N,N-bis(2-chloroethyl)aminocinnamates, in which the alkylating agents are linked to the modified steroid in the axial position, are inactive in the above experimental animal tumor systems. The effect of the homo-aza-steroidal esters of N,N-bis(2-chloroethyl)aminocinnamic acid isomers on the incorporation of radioactive precursors into DNA, RNA, and proteins of L1210, P388 leukemias, Ehrlich ascites tumor, and baby hamster kidney cells was investigated. Higher inhibitory effects on the incorporation of the radioactive precursors was obtained with the ortho-derivatives, yielding > 40% inhibition of thymidine incorporation in all tumor lines tested. The effect of four esters in which the m N,N-bis(2-chloroethyl)aminocinnamic acid is linked to the modified steroids on sister chromatid exchanges in human lymphocyte culture was investigated. PMID- 8445537 TI - Bioavailability and bioequivalence of two formulations of etodolac (tablets and suppositories). AB - We studied the influence of administration route on the biopharmaceutical behavior of etodolac. The levels obtained in plasma when the same dose of etodolac is administered orally (tablets, dosage form A) and rectally (suppositories, dosage form B) were compared. The study was done in a crossover design with healthy volunteers of both sexes, of average build, and younger than 35 years of age. From the concentration in plasma-time data, the maximum concentration in plasma (Cmax), time to Cmax, and area under the curve up to the last measurable concentration (AUC0t) or infinity (AUC 0 infinity) were calculated and compared by analysis of variance. With the exception of Cmax, no significant differences between treatments were found in the rest of the parameters. Finally, with formulation A (tablets) as a reference, the relative bioavailability was established, on the basis of the ratio (B:A) of AUC0t and AUC 9 infinity, within the range 100 +/- 20%. The results indicate that the two routes of administration are bioequivalent and that the rectal route is an alternative administration route for etodolac. PMID- 8445538 TI - Facilitated transport of two model steroids by esters and amides of clofibric acid. AB - A series of novel dermal penetration enhancers, esters and amides of clofibric acid, was synthesized. The permeation parameters and skin retention of two steroids (hydrocortisone-21-acetate and betamethasone-17-valerate) in propylene glycol were studied with athymic nude mouse skin by in vitro diffusion cell techniques in the presence of the novel enhancer compounds. Isopropyl myristate, dimethyl lauramide, and 1-dodecylazacycloheptan-2-one (laurocapram, Azone) were used as control enhancers. The most satisfactory enhancement of both the ester and amide series was observed with clofibric acid octyl amide; coadministration increased skin retention of hydrocortisone acetate after 24 h by 3.5-fold and that of betamethasone valerate by 2.9-fold. Diffusion cell receptor concentrations increased 51.6- and 10.3-fold, respectively, during the same time period. However, the enhancer compound in this case was applied to the skin 1 h prior to each of the steroids. The amide analogues were more effective than the equivalent ester compounds of the same carbon chain length. The best enhancer compounds (2c, 3d, 3e, and 3f) were nonirritating to athymic mouse skin in vivo. PMID- 8445539 TI - Effect of the mode of super disintegrant incorporation on dissolution in wet granulated tablets. AB - The effect of the mode of super disintegrant incorporation in wet granulated tablets was investigated with three super disintegrants: sodium starch glycolate, crospovidone, and croscarmellose sodium. The disintegrants were incorporated extragranularly or intragranularly or distributed equally between the two phases. Lactose, naproxen, or dibasic calcium phosphate was used as the principal tablet component to provide various degrees of solubility to the formulations. The formulations were dried to three different levels of moisture content. The results indicated that, for the formulations studied, extragranular incorporation resulted in faster dissolution than did equal distribution intragranularly and extragranularly, which in turn was superior to intragranular incorporation. Granulation moisture content was found to have a formulation-specific impact on tablet dissolution, with each main tablet component behaving in a different fashion. When all other factors were kept constant, there was a tendency for croscarmellose sodium to produce faster tablet dissolution than sodium starch glycolate or crospovidone. The super disintegrants tended to promote faster dissolution in a neutral pH medium than in an acidic medium. PMID- 8445540 TI - Testosteronyl-4-dimethylaminobutyrate-HCl: a prodrug with improved skin penetration rate. PMID- 8445541 TI - Kinetics of drug action in disease states. XLII. Effect of repeated blood sampling on the pharmacodynamics of phenobarbital in rats. PMID- 8445542 TI - Microradiography and light microscopy of mineralization in the pulp of undemineralized human primary molars. AB - This study was undertaken to investigate the prevalence, location and histologic features of the different types of mineralization observed in the pulp of human primary molars. Microradiography and light microscopy of undemineralized material disclosed that 95% of primary molars contain pulp calcifications. Histologically, their structure may be classified into four different types: (1) pulp stones, (2) diffuse calcifications, (3) eburnoid tissue and (4) spherulitic calcifications. PMID- 8445543 TI - Oral candidiasis established in the sialoadenectomised rat. AB - Xerostomia provoked in rats by surgical removal of the major salivary glands favoured the development of oral candidiasis. After 32 weeks of inoculation, 20% of normal and 70% of xerostomic rats showed candidal infection on the tongue but only in xerostomic rats did candidiasis affect the pharyngeal aspect of the tongue. PMID- 8445545 TI - A retrospective evaluation of 193 patients with oral lichen planus. AB - One hundred and ninety-three patients with oral lichen planus were evaluated retrospectively. Women outnumbered men by more than two to one. The mean age at lesion discovery was in the sixth decade. The buccal mucosa was the most common site of occurrence. There were concomitant systemic diseases in many of the patients. The ulcerative form was the most prevalent referred form. Therapies included observation and treatment with topical and systemic corticosteroids with and without anti-fungals and immunosuppressants. Areas of discussion include lesion location, chronicity, therapeutic modalities, malignant transformation, age, gender, symptomatology and systemic disease. PMID- 8445544 TI - HLA-DR and DQ antigens in Chinese patients with Behcet's disease. AB - The frequencies of HLA-DR and DQ antigens in 24 Chinese patients with Behcet's disease (BD) were calculated and compared with those in 130 healthy control Chinese and those in 80 Chinese patients with recurrent oral ulcers (ROU). Although an increased trend of DRw6 and DRw8 antigens in patients with BD was noted, there was no significant difference in frequencies of HLA-DR and DQ antigens between patients with BD and healthy control subjects or patients with ROU after correction of P values (Pc > 0.05). Further analysis of our data of the phenotype frequencies of DRw6 and DRw8 antigens according to the subtypes of BD also showed the increased frequencies of DRw6 and DRw8 antigens in patients with mucocutaneous type of BD as compared with those in healthy control subjects. However, only the phenotype frequency of DRw8 antigen in patients with mucocutaneous type of BD was significantly higher than that in patients with ROU (P < 0.005, Pc < 0.05, relative risk = 17.7, and etiologic fraction = 0.30). This significant increase of the phenotype frequency suggests that the gene coding for HLA-DRw8 antigen in patients with ROU was only partially (30%) responsible for susceptibility to the mucocutaneous type of BD. PMID- 8445546 TI - Aminotransferases and lactate dehydrogenase in saliva of diabetic patients. AB - Although inflammatory or degenerative changes in salivary glands have been demonstrated in genetic animal models of diabetes mellitus and in experimental diabetes, no information is available in diabetics on the possible leakage in saliva of cytosolic enzymes as markers of salivary cell injury. Aspartate (GOT) and alanine (GPT) aminotransferases and lactate dehydrogenase (LDH) were determined in saliva samples collected by the Salivette method from well controlled insulin-dependent (IDDM n = 11) and non-insulin-dependent (NIDDM n = 18) diabetic patients and from age-cross-matched healthy subjects (n = 33). In IDDM salivary concentrations of GOT (112.55 +/- 23.94 UI/L) and LDH (1120.27 +/- 168.31 UI/L) were similar to those found in the NIDDM (90.94 +/- 19.64, and 1255.43 +/- 221.40 UI/L respectively), but higher (p < 0.05) than those observed in normal subjects (33.09 +/- 3.71, and 423.58 +/- 39.94, UI/L respectively). GPT was higher in NIDDM than IDDM, which in turn was higher than in normal subjects (42.78 +/- 14.72, 16.45 +/- 3.74 and 6.85 +/- 1.52 UI/L respectively). Salivary and serum values of GOT, GPT and LDH were not correlated. Determination of cytosolic enzymes in saliva may be useful for monitoring the diabetic involvement of salivary glands. PMID- 8445547 TI - Nucleolar organiser region (NOR) distribution as a diagnostic marker in oral keratosis, dysplasia and squamous cell carcinoma. AB - Nucleolar organiser regions (NORs) were quantified from a range of oral mucosal biopsies (n = 40) consisting of benign, reactive, dysplastic and carcinomatous lesions, using silver (Ag) staining, to see if AgNOR counts were helpful in distinguishing them. Mean counts were greater in carcinomas (8.37 +/- 6.11) compared to epithelial dysplasias (5.61 +/- 4.63) or benign keratoses (4.51 +/- 2.57). Although these differences were significant, counts in each diagnostic group overlapped so much that they were of no practical value in distinguishing between individual lesions. However, the higher counts found in many carcinomas were due to dispersion of AgNORs within the nucleoplasm, so that the AgNOR type is helpful in making such a distinction. Whether those dysplastic lesions with higher and more dispersed counts represent those at greater risk of malignant transformation awaits longitudinal study. PMID- 8445548 TI - Oral findings in Mexican AIDS patients with cancer. AB - Oral findings of 42 Mexican AIDS patients with cancer were reviewed. Kaposi's sarcoma (KS) was the most frequent malignancy (81%) followed by non-Hodgkin's lymphoma (NHL) (12%). All cases of NHL were of high or intermediate grade and most of them were extranodal. Out of the 34 individuals with KS, 22 (65%) showed oral KS and in 21 of them the palate was involved. The clinical features of oral KS including site, appearance and size are described. Pseudomembranous candidosis (PC), hairy leukoplakia (HL) and exfoliative cheilitis (ECh) were also found in these patients. There was no association of these lesions with any type of cancer. A strong association of oral candidosis and history of this infection was found, RR = 7.0 (1.3-4.1). There was evidence of severe immunosuppression in most patients, with mean average CD4 counts of 116 mm3 (range 4-841/mm3). Oral KS, ECh, PC and HL were more common in patients with lower CD4 counts. Our findings illustrate the most frequent oral lesions associated with HIV-1 infection in patients with AIDS and cancer, and further support the importance of oral examination in HIV infected patients. PMID- 8445549 TI - Pemphigus vulgaris precipitated by glibenclamide therapy. AB - Pemphigus vulgaris (PV) is a rare but potentially fatal autoimmune bullous disorder which frequently affects the oral mucosa. Although the essential cause of PV is unclear, its onset has occasionally been associated with drug therapy, in particular penicillamine. The patient described in this paper was a 78-year old diabetic man who developed oral lesions of PV following institution of glibenclamide therapy. PMID- 8445550 TI - Allergic sensitivity to several base metals: a clinical report. PMID- 8445551 TI - A flexible lingual clasp as an esthetic alternative: a clinical report. PMID- 8445552 TI - Peroxide bleaches: effect on tensile strength of composite resins. AB - Research concerning bleaching agents on the mechanical properties of composite resin restorative materials has produced conflicting reports. Representative brands of composite resin restorative materials were studied, including microfil, hybrid, and posterior types. The bleaching agents selected were 30% hydrogen peroxide and two commercial brands of 10% carbamide peroxide. Ten specimens of each material, prepared according to American National Standards Institute/American Dental Association specification No. 27 for diametral tensile testing, were stored in bleaching agents for 1 hour and 168 hours at 37 degrees C. An equal number of specimens stored in deionized water with identical conditions were designated controls. Qualitative examination of bleached specimens revealed a marked change in color, especially the microfilled composite resins. There was no significant difference in tensile strength between controls and exposed samples at either time except for the diminished strength of microfilled composite resins in 30% hydrogen peroxide for one week (p < 0.01). PMID- 8445553 TI - Effects of disinfecting irreversible hydrocolloid impressions on the resultant gypsum casts: Part I--Surface quality. AB - This study evaluated the effects of disinfection time (10, 30, and 60 minutes) on the surface quality of stone casts poured against an alginate impression material (Jeltrate). Five antimicrobial agents were tested: Sporicidin spray, sodium hypochlorite, and iodophor for spray; and Sporicidin cold sterilization solution and Cidexplus glutaraldehyde solution for immersion. Impressions, flushed with water and stored for 0, 10, 30, and 60 minutes before pouring, served as untreated controls. On completion of the disinfection treatments, the impressions were rinsed and poured in Velmix stone. The effects on cast surface were evaluated under a stereomicroscope by three experienced raters. A 1-to-4 scoring system was developed to rate the surface quality in terms of smoothness and detail reproduction. Both immersion disinfectants proved to be unacceptable for treating alginate impressions. The mean scores of other disinfectant-time combinations were compared with the use of the Tukey-Kramer method with a 95% confidence interval. The results indicated that treatment time had statistically significant effects on the quality of cast surface in Sporicidin spray, sodium hypochlorite, and untreated control groups but not in the iodophor spray group. PMID- 8445554 TI - Retentive characteristics of an internally threaded post system. AB - Internally threaded, stainless steel posts 10 mm in length and 1.82 mm in diameter or stainless-steel Para-Post dowels 1.7 mm in diameter were cemented in extracted human teeth with zinc phosphate cement. Titanium alloy screws 1.5 mm in diameter were placed in the internally threaded posts and tensile force was applied to the screws or Para-Post dowels until dislodgment of the post or fracture. The retention of the Para-Post system was significantly greater than the experimental posts. Although all screws exhibited deformation, there was no breakage or distortion of the internally threaded posts or Para-Post dowels. Retention for both systems exceeded reported forces generated in humans. PMID- 8445555 TI - Comparison of the retention of endodontic posts after preparation with EDTA. AB - Significant differences in the retention of preformed endodontic posts for endodontically treated teeth were determined with (1) parallel-sided, passively placed Para-Post dowel versus mechanically engaging, threaded Flexi-Post dowel; (2) irrigation of canals with EDTA; (3) cementation with urethane dimethacrylate resinous or zinc phosphate cement. It was hypothesized that EDTA would substantially increase retention by removing the smear layer on the prepared canal wall and create micromechanical retention in the dentin. Extracted teeth were prepared with endodontic posts and divided in groups representing combinations of variables. The forces for post removal and the locations of the retentive bond failures were recorded. The results indicated that EDTA did not significantly affect retention. The Flexi-Post dowel was significantly more retentive than the Para-Post dowel but also exhibited a greater potential for tooth damage compared with the Para-Post dowel during retentive failure loads. PMID- 8445556 TI - Microhardness evaluation of a two-piece post and core technique. AB - This study compared the microhardness of one- and two-piece cast post cores. Twenty 0.070 inch Whaledent "burn-out" posts were invested in a phosphate investment, cast, and bench cooled to room temperature. Five samples, were grouped by Sturdicast or Midas metal and by casting technique. The specimens were cast in matched pairs with one of each technique per casting ring. The Vickers hardness number sites were centered on the post diameter with the core-to-post head junction used as a baseline, at the following sites: (1) 1.5 mm into the core to post head assembly; (2) at the junction of the post to the post head and core assembly; (3) 1 mm into the post; (4) 2 mm into the post; and (5) 3 mm into the post. There were no significant differences in microhardness at the sites tested for metal or casting technic (p < 0.05). This indicated that a two-piece post and core has similar hardness values to the one-piece casting. PMID- 8445557 TI - Cephalometric evaluation of the changes in patients wearing complete dentures: a 20-year study. AB - The purpose of this continuing longitudinal investigation was to study the changes on the craniofacial complex in complete denture wearers; herein are reported the 20-year findings. At the onset of the study complete dentures were made for 64 persons. Two dentures techniques were employed: a complex method of construction and a simplified method. At the start of the project the patients' ages ranged from 30 to 60 years (average age 53 years) and all had been edentulous for at least 1 year (range 1 to 30 years). Lateral cephalometric radiographs were made immediately after initial placement of the dentures and during subsequent years (1, 2, 3, 4, 5, 7, 10, 15, and 20). The same cephalostat was used throughout and all films were exposed with the teeth in centric occlusion. Thirty-four subjects presented for the 20-year follow-up. Of this number, the radiographs of 24 subjects (14 women and 10 men; average age 65.5 years [range 50-83 years]) (12 complex denture wearers; 12 simplified technique denture wearers) were used in this report (10 had denture alterations over the 20 year period that excluded them). The 20-year observations corroborate earlier findings. There is a loss of the vertical dimension of occlusion as viewed from the right profile, and the mandible rotates in a counterclockwise fashion resulting in an increase in relative prognathism. The maxillary alveolus was stable, the mandibular alveolus resorbed, and the dentures rotated counterclockwise and shifted slightly forward. The observed changes were not significantly affected by the sex of the patient or by the denture technique employed. PMID- 8445558 TI - A dual-purpose stent for the implant-supported prosthesis. AB - Osseointegrated implants are a practical alternative to traditional prosthodontics; however, designing an implant-supported prosthesis with function and esthetics is a challenge. When the available bone or the location of vital structures is questionable, computed tomography (CT) is indispensable for diagnosis and treatment planning. This article describes a stent that implements the information from a CT scan and is then modified to guide the surgical placement of the implants. PMID- 8445560 TI - Prosthetic complications of extraoral implants. AB - The use of tissue-integrated fixtures for the retention of an extraoral prosthesis has simplified the placement, removal, and cleaning of the prosthesis by the patient. Tissue evaluation, structural designs, and retention mechanisms, combined with patient compliance and the ability to perform hygiene around retentive substructures, has produced an array of new problems. Clinical and technical problems are presented with techniques used in their resolution. PMID- 8445559 TI - The effects of early occlusal loading on one-stage titanium alloy implants in beagle dogs: a pilot study. AB - The initial stages of bone healing with titanium alloy implants were compared clinically and histologically in three groups of beagle dogs: unloaded one-stage (group 1), loaded one-stage (group 2), and unloaded two-stage (group 3). No implant mobility was reported in any of the three groups. For the most part direct bone contact was achieved, but there was a significant difference in the histologic results of the interface among the animals in all three groups. Significant crestal bone loss was evident in group 2, which showed poor bone apposition to the bottom of the threads in the upper portion of the implant. New bone growth to these same areas of the threads was seen in the animals in groups 1 and 3, with the ratio of direct bone contact significantly higher for those in group 3. These differences could be attributed to the effect of early occlusal loading on the implant during initial bone healing. PMID- 8445561 TI - Effect of a full-arch maxillary occlusal splint on parafunctional activity during sleep in patients with nocturnal bruxism and signs and symptoms of craniomandibular disorders. AB - This study was designed to investigate the effects of the occlusal splint on parafunctional oral motor behavior (grinding and clenching) during sleep in patients with bruxism and craniomandibular disorders. The results revealed that the splint does not stop nocturnal bruxism. In 61% of the patients, wear facets on the splint were observed at every visit (2-week intervals) and in 39%, from time to time. The wear facets reappeared in the same location with the same pattern and were caused mainly by grinding. The extension of the facets showed that, during eccentric bruxism, the mandible moved laterally far beyond the edge to-edge contact relationship of the canines. PMID- 8445562 TI - Temporomandibular joint sounds in asymptomatic volunteers. AB - Abnormalities within the temporomandibular joints often produce audible sounds. Electronic recording of joint sounds has been used as a method of staging internal derangement. This study had three objectives: first, to determine whether the characterization of temporomandibular sounds can provide a sensitive and accurate measure for the presence or absence of joint abnormalities in asymptomatic volunteers; second, to evaluate the reproducibility of the sounds, when present, with successive recordings; and third, to evaluate the sound characteristics to determine their predictability for the types of internal derangement. Fifty asymptomatic volunteers (100 joints) were evaluated with an electronic device for the presence of joint sounds. Of the patients, 24% (N = 50, five men and seven women) (16% of all joints) had one or two abnormal joints as diagnosed by magnetic resonance imaging. Forty-four percent of all joints had identifiable sounds; 50% of the sounds were produced when the condyle was located at the apex of the articular eminence. Sounds often occurred in the early opening phase of jaw movement in joints diagnosed as normal by magnetic resonance imaging. Finally, the characteristics of these events did not produce adequate separation to stage the internal derangement. PMID- 8445563 TI - Masseter muscle fatigue during sustained clenching in subjects with complete dentures, implant-supported prostheses, and natural teeth. AB - A sustained submaximal (50%) clenching effort was performed in four patient groups to establish whether implant-supported prosthetic reconstructions influence myoelectrical signal parameters. The first group consisted of patients with natural teeth in both jaws. The other three groups consisted of patients who were edentulous in both jaws: one group had complete dentures; one had an overdenture in the mandible on two implants connected by a bar; and the third had an implant-supported fixed prosthesis in either the maxilla or the mandible. Surface electromyography indicated an increased myoelectrical output level that paralleled a higher bite force level for implant-supported reconstructions compared with complete dentures. Power spectrum analysis revealed a downward shift of the mean power frequency during sustained clenching in all groups except the implant-supported fixed prosthesis. The absence of a spectral shift in the latter group probably reflected a fear of biting too hard and fracturing the prosthesis. PMID- 8445564 TI - Denture adhesives: cytotoxicity, microbial contamination, and formaldehyde content. AB - Denture adhesives are extensively used to enhance retention of dentures. Denture adhesives and their leachable components are ingested, but reports on the biologic aspects of denture adhesives are scarce. This study investigated some biological properties of 19 commercially available denture adhesives. The adhesives were assessed by the agar overlay technique and analyzed for microbial contamination and formaldehyde content. In the agar overlay test, all of the materials caused severe cytotoxic effects. Sabouraud dextrose agar was used for cultivation of fungi and tryptone soya broth for cultivation of aerobes, including fungi. Most of the samples tested showed microbial growth. The formaldehyde test revealed the presence of substantial amounts in four products and minor amounts in two products. PMID- 8445565 TI - Surface treatment of a temporary soft liner for increased longevity. AB - This is a preliminary report on the use of several surface-conditioning agents on a commonly used temporary soft lining material. The surface of the material was treated with either poly(ethyl methacrylate) monomer, mono-poly glaze, or Minute Stain glaze. Samples were compared with untreated soft liner before and after it was worn by a patient for 30 days. The scanning electron microscope was used to analyze samples. Initially the surface of all samples was intact, with the samples treated with mono-poly glaze and Minute-Stain glaze having fewer irregularities. After 30 days, untreated liner and that treated with monomer showed severe wear with resultant exposure of generalized pits and holes. Most of the defects represented exposure of subsurface air bubbles incorporated during mixing. The mono-poly glaze-treated specimen retained the glasslike appearance that it had before it was worn for 30 days. The Minute-Stain glaze specimen appeared irregular, although without the extensive pitting seen in the first two types of specimens. PMID- 8445566 TI - Bleaching: is it safe and effective? AB - It has been well documented that bleaching whitens teeth, but has its safety been documented? This paper reviews bleaching's predictability, esthetics, longevity, and side effects. A discussion of the bleaching reaction on teeth and soft tissue raises concerns over the safety of the procedure. PMID- 8445567 TI - A silicone rubber spacer used to determine the optimum thickness for hard and resilient materials in complete dentures. AB - When making a denture with a resilient lining, the problem of controlling the thickness of the resilient lining material is eliminated by use of a spacer. However, controlling the thickness of the hard acrylic resin denture base in these dentures remains a problem and may increase the possibility of fracture. When limited denture space is available, the portions of the denture base subject to fracture should have an accurate if not equal share of the resilient lining material and the hard acrylic resin material. This procedure will minimize the fracture problem of dentures made with resilient lining and is an alternative to conventional spacer procedures. PMID- 8445568 TI - Investigation on the compressive strength of several gypsum products dried by microwave oven with different programs. AB - Different programs in a microwave oven were selected to dry several gypsum products. A type III dental stone (Moldano), a type IV high-strength dental stone (Glastone) and a type III partial denture casting investment (Multi-vest) were selected. Specimens of the products were dried by microwave radiation set at the lowest and highest power levels for 5 and 15 minutes. The dried specimens were tested at intervals of 2, 4, 24, and 48 hours for compressive strength. Specimens dried in ambient room air were used as the control group. A statistical analysis of the test results was performed with Student's t-test at p < or = 0.05 level. Microwave radiation at the highest power level resulted in a decrease in the compressive strength of type IV dental stone (Glastone), whereas the values of the other gypsum products did not differ at any time interval from values attained for the air-dried specimens. The 2-hour low power test of the investment (Multi-vest) had a higher compressive strength than the air-dried specimens after 24 hours. PMID- 8445569 TI - Microwave processing for denture relines, repairs, and rebases. AB - The microwave processing procedure has been shown to be an efficient and accurate method of polymerizing poly(methyl methacrylate) resin for the fabrication of dentures. This article describes procedures to expand the uses of the microwave technique. With standard laboratory procedures, the microwave technique can improve and simplify denture relines, repairs, and rebasing of partial dentures. PMID- 8445570 TI - Removing broken abutment screws from internally threaded implants. PMID- 8445571 TI - Repair of urethane silicone prostheses. PMID- 8445572 TI - An automated water measure for mixing irreversible hydrocolloid. PMID- 8445573 TI - Esthetic veneers for use with forced eruption procedures. PMID- 8445574 TI - Use of tin plating instrument to strengthen the bond between metal and a resin luting agent. PMID- 8445575 TI - Jaw records for the edentulous patient made easier. PMID- 8445576 TI - Fabrication of an implant stent for the edentulous mandible. PMID- 8445577 TI - Do frogs use retinal elevation to measure the distance of a barrier? AB - Grass frogs, Rana pipiens, will detour around a barrier to reach prey on the other side. However, if the distance between prey and barrier is short, frogs attempt to push through the barrier and reach the prey directly. The relationship between the probability of detouring and the distance between prey and barrier is the same whether the frog's starting position is 4 cm or 8 cm from the barrier. This suggests that frogs measure the absolute separation between the two objects. To discover whether the retinal elevation of the bottom of the barrier contributes to measuring this distance, the relationship between the frequency of detouring and barrier-prey distance was examined in several experiments in which the retinal position of the bottom of the barrier was manipulated. No evidence was obtained that the barrier's retinal elevation helps in gauging distance. On the other hand, retinal elevation influences strongly how far a frog lunges to reach its prey. It is suggested that different cues to distance are applied to the two classes of object because, under natural circumstances, it is difficult to judge where a barrier emerges from the ground. A barrier may be hard to detect below the horizon because of the low contrast between it and the ground, or because vegetation and ground litter mask where the barrier meets the ground. In contrast, the prey's movements make it easily detectable against a stationary background and the prey's short height means that partial occlusion will have little effect on its apparent vertical position in the visual field. PMID- 8445578 TI - In vivo buccal nerve activity that distinguishes ingestion from rejection can be used to predict behavioral transitions in Aplysia. AB - 1. We are studying the neural basis of consummatory feeding behavior in Aplysia using intact, freely moving animals. 2. Video records show that the timing of radula closure during the radula protraction-retraction cycle constitutes a major difference between ingestion (biting or swallowing) and rejection. During ingestion, the radula is closed as it retracts. During rejection, the radula is closed as it protracts. 3. We observed two patterns of activity in nerves which are likely to mediate these radula movements. Patterns I and II are associated with ingestion and rejection, respectively, and are distinguished by the timing of radula nerve activity with respect to the onset of buccal nerve 2 activity. 4. The association of ingestion with pattern I is maintained when the animal feeds on a polyethylene tube, the same food substrate used to elicit rejection responses. Under these conditions, pattern I is associated with either swallowing or no net tube movement. 5. Most transitions from swallowing to rejection were preceded by one or more occurrences of pattern I in which there was no net tube movement, suggesting that these transitions can be predicted. 6. Our data suggest that these two patterns can be used to distinguish ingestion from rejection. PMID- 8445579 TI - Different ionic conductances are modulated during the late receptor potential and the prolonged depolarizing afterpotential in Hermissenda type A photoreceptors. AB - Wavelength-dependent, bistable phenomena were found in the receptor potential of Hermissenda crassicornis type A photoreceptors. Short exposure to blue light induced a prolonged depolarizing afterpotential (PDA) following the cessation of the light stimulus. Stronger adaptation to blue light, as caused by prolonged exposure and/or high intensity stimulation, effected a reduction in the early depolarizing transient of the late receptor potential (LRP) as elicited by subsequent stimuli. Vast separation of LRP emergence and PDA emergence could be obtained in photoreceptors in which a strong cancellation of the LRP was accomplished but a PDA still emerged after cessation of the light stimulus. Short exposure to yellow light cancelled the PDA, and stronger adaptation restored the LRP (opposite effect to blue light). The initial depolarizing part of the LRP had earlier been demonstrated to be mediated by the light-dependent increase of an inward conductance. In contrast, in this study the PDA was found to be accompanied by the reduction of an outward conductance, most likely a K+ conductance. A bistable photopigment system is thought to control the bistable receptor potential phenomenology by regulating the different membrane conductances during the LRP and the PDA. PMID- 8445580 TI - Periodicity extraction in the anuran auditory nerve. I. "Pitch-shift" effects. AB - 1. Activity of individual eight nerve fibers in the bullfrog, Rana catesbeiana, was measured in response to complex, multiple-frequency stimuli differing in both frequency composition and harmonic structure. Stimuli were chosen to parallel types of stimuli producing "pitch-shift" effects in humans. 2. The fundamental frequency of harmonic stimuli can be extracted from the autocorrelation of fiber firing, whether the fundamental is physically present in the stimulus or is a "missing" fundamental. The spectral fine-structure of harmonic stimuli is not robustly represented in fiber temporal response. These effects are seen in both AP and BP fibers. 3. The pseudoperiod of inharmonic stimuli is represented by synchronization to successive high-amplitude peaks in the stimulus envelope. Temporal responses to stimuli with high center frequencies are similar regardless of whether their frequency components are harmonically or inharmonically related. Responses remain dominated by the envelope periodicity, and no "pitch-shift" is signaled. In response to stimuli with low center frequencies, temporal responses signal a "pitch-shift" between harmonic and inharmonic complexes. Both AP and BP fibers show these effects. 4. These data suggest that bullfrog peripheral fibers extract the periodicity of complex stimuli by time-domain rather than frequency domain coding. PMID- 8445581 TI - A sensory map based on velocity threshold of sensory neurones from a chordotonal organ in the tailfan of the crayfish. AB - The central projections of sensory neurones innervating a strand chordotonal organ (CO) in the tailfan of the crayfish, Procambarus clarkii (Girard) have been investigated. The CO monitors movement of the exopodite of the tailfan relative to the endopodite. Intracellular recording and staining were used to characterise the response of the sensory neurones to applied stretches of the chordotonal organ and to reveal their morphology. Two gross morphological types of afferents were found: those that terminated in the terminal (6th) abdominal ganglion on the side ipsilateral to the sensory receptor, and those that had branches in the terminal ganglion and an intersegmental axon that ascended rostrally. Afferents responded to position, velocity and direction of imposed CO displacement. Afferents with particular physiological properties had similar morphologies in different crayfish. Irrespective of their directional responses, afferents had central projection areas dependent upon their velocity thresholds. Many afferents responded only during movement of the CO, and those with the lowest velocity thresholds (2 degrees/s) had branches that projected most anteriorly, while those with progressively higher velocity thresholds (up to 200 degrees/s) projected progressively more posteriorly. Afferents that responded to low velocity ramp movements and spiked tonically projected to more posterior areas of the ganglion than those that responded only to movements. PMID- 8445582 TI - Sleep disturbances in respiratory and cardiovascular disease. AB - It has long been recognised that patients with respiratory and cardiac disease suffer from symptoms during the night when they would normally be seeking respite. These disturbances include nocturnal dyspnea, cough, wheezing and angina. Until the advent of polysomnographic monitoring about 25 yr ago, however, the pathophysiology of these nocturnal disturbances remained elusive. Since that time, investigators have made significant advances in the understanding of the pathogenesis of many of these disturbances which will be briefly reviewed below. As the subject of this article is disturbances of sleep in patients who suffer from respiratory and cardiac disease, the sleep apnea syndromes which are unique to sleep, will not be discussed except as they may contribute to symptoms of respiratory and cardiovascular disease. PMID- 8445583 TI - The nuts and bolts of behavioral therapy for insomnia. PMID- 8445584 TI - Insomnia in neurological diseases. AB - Sleep disturbance, common in many neurological diseases, can be caused by underlying CNS pathology, altered motor system function, associated cognitive and psychiatric disorders, secondary effects of the disease such as pain and immobility, and medication effects. Nocturnal behavioral disturbances are a major contributor to institutionalization of such patients, and respiratory abnormalities of sleep can be life-threatening. Rational approach to diagnosis and treatment can lead to significant improvements in many such patients. PMID- 8445585 TI - A group approach for the management of insomnia. AB - To date, the management of insomnia has primarily consisted of pharmacological and behavioral approaches for individual patients. This paper documents the authors' work in formulating a group intervention for patients suffering from insomnia. The treatment rationales are discussed and include group theory, cognitive-behavioral and educational frames of reference. A description of the techniques used and the structure and process of the group model used is provided. PMID- 8445586 TI - The difficult to treat insomniac patient. AB - When a complaint of significant insomnia does not respond to standard interventions, the clinician must reassess the diagnosis with particular emphasis on psychiatric or psychological factors. This article describes the management of patients with 'sleeping pill insomnia,' insomnia associated with affective illness, sleep state misperception, 'sick role' behavior and treatment non compliance. PMID- 8445587 TI - Alleviating sleep-related discontinuance symptoms associated with benzodiazepine withdrawal: a new approach. AB - There is limited information on the time course of recovery of sleep architecture in patients withdrawn from benzodiazepines (BDZ). This study examined the effects of substituting a new class of hypnotic drugs, namely the cyclopyrrolones, for current BDZs in patients presenting with BDZ dependence. The results indicated a clear improvement in a variety of sleep parameters after commencing with a cyclopyrrolone (zopiclone). These changes remained to some extent after zopiclone was discontinued. Also, the absence of certain withdrawal effects (i.e. rebound insomnia) upon discontinuation of zopiclone allows for patients to be carried through a potentially difficult period after stopping BDZs, while expediting the eventual discontinuation of all hypnotic medication. PMID- 8445588 TI - Hypnotics should never be used in patients with sleep apnea. AB - Although benzodiazepine medication is generally considered to be inappropriate for patients with obstructive sleep apnea, further investigation is required to evaluate this. Non-benzodiazepine hypnotics may improve sleep quality without causing respiratory depression. In central sleep apnea, hypnotics not only improve sleep but also decrease apnea frequency probably by reducing arousals and elevating arterial PCO2. Consequently, I submit that the statement 'hypnotics should not be used in patients with sleep apnea' should be changed to 'hypnotics may sometimes be used in patients with sleep apnea'. PMID- 8445589 TI - Lyme disease in military personnel. AB - The tick responsible for Lyme disease is common in areas inhabited by deer. This should theoretically put military personnel at increased risk. A history of tick bite is uncommon and the characteristic skin rash often absent. Two examples of servicemen with neurological Lyme disease without cutaneous manifestations are discussed, and six other cases referred to the RAF Institute of Pathology and Tropical Medicine since 1987 briefly reviewed. Five of the cases contracted the disease in Germany and four were dependents. Lyme disease is under-recognised and under-reported, so that the scale of the problem cannot be determined. It is recommended that wooded areas inhabited by deer should not be frequented without adequate clothing, particularly in the early summer months when tick activity is at its greatest. PMID- 8445590 TI - Recurrent bacterial meningitis and impaired host defences. AB - Recurrent pyogenic meningitis is uncommon. Its aetiology is often associated with impaired host defence mechanisms. Two such examples are discussed. Case 1 resulted from an anatomical defect and Case 2 a defect of the complement system. PMID- 8445591 TI - Rove beetle blistering--(Nairobi Eye). AB - 'Nairobi Eye' is a condition caused by a blister beetle, Paederus eximius, found in Northern Kenya. It has not previously been described as a hazard for troops exercising in this area. Four cases are described. Recommended management is to wash the contact area initially with soap and water, and to treat subsequent lesions with flamazine. PMID- 8445592 TI - The basal cell naevus syndrome: a case in the Falkland Islands. AB - A case of basal cell naevus syndrome is presented. The jaw cysts were proved histopathologically to be odontogenic keratocysts. The multiple naevoid lesions on the skin were identified as basal cell carcinoma. Intracranial calcification is illustrated to a degree not previously reported in a case with this syndrome. The importance of identifying this syndrome is discussed and its presentation in the Falkland Islands is reported. PMID- 8445593 TI - Deep seated infection due to Lactobacillus caseii. PMID- 8445594 TI - Pre-peritoneal prosthetic repair of recurrent inguinal herniae. PMID- 8445595 TI - Advanced trauma life support. PMID- 8445596 TI - Experiences in a level-1 trauma centre-report. PMID- 8445597 TI - Exercise-induced injuries--management or prevention? PMID- 8445598 TI - Communicable disease control. PMID- 8445599 TI - Medical standardisation issues from operations. The Canadian perspective. PMID- 8445600 TI - Vulvar involvement in autoimmune bullous diseases. AB - The autoimmune blistering diseases are characterized by involvement of the skin and mucous membranes. On mucosal surfaces, although the initial lesion is often a blister, friction results in erosions. We report on 140 female patients with a variety of blistering diseases examined in the bullous disease clinic. Vulval involvement was found in 5 of 55 adult patients and in 2 of 3 girls with bullous pemphigoid. Sexual abuse was initially suspected in one child. Twenty-six women had cicatricial pemphigoid; of these, 14 had vulval involvement, often with severe scarring. Chronic bullous disease of childhood was identified in 20 girls; perineal involvement was present in 16 causing initial misdiagnosis of herpes simplex in one case and sexual abuse in another. Vulval involvement was less frequent in linear IgA disease (the adult counterpart of chronic bullous disease of childhood), occurring in 9 of 22 patients. One of two adults and two of three girls with epidermolysis bullosa acquisita had vulval involvement. Finally, of nine female patients with pemphigus, four had vulval involvement, all of whom had pemphigus vulgaris. Blistering diseases are rare, but vulval involvement is common across the spectrum of these diseases. When mucosal involvement predominates, diagnostic difficulties can arise. PMID- 8445601 TI - Primary adenocarcinoma of the vulva, possibly cloacogenic. A report of two cases. AB - Primary adenocarcinoma of the vulva, arising in continuity with the epidermis and unrelated to the underlying mucus glands, is a distinctly uncommon neoplasm. The origin of such an unusual tumor, although attributed to cloacal remnants, remains speculative. We describe two patients with this rare lesion. No other primary tumor was found in either of the two after a thorough investigation. One patient was treated with radical vulvectomy and was free of disease for 10 years, until her death from unrelated causes. The second patient was treated with wide local excision and was free of disease four years postoperatively. Our experience indicates the need to recognize this tumor as a primary and not metastatic neoplasm of the vulva. We also noticed that in both cases, despite its histologic malignancy and ulceration, the tumor was superficial in its extent and without any tendency for deeper invasion. It can therefore be treated effectively with wide local excision, thus eliminating the need for radical vulvectomy. PMID- 8445602 TI - Laparoscopic evaluation of the argon beam coagulator. Initial report. AB - The objective of this study was to evaluate the safety and hemostatic properties of the argon beam coagulator (ABC) at laparoscopy. The study is composed of two parts: laparoscopic results in five anesthetized animals and a preliminary clinical trial in 35 volunteers undergoing laparoscopy. Animals were evaluated during a laparoscopic cholecystectomy training course. Private patients undergoing operative laparoscopy voluntarily consented to a hospital Investigational Review Board-approved protocol to evaluate the ABC. The pigs were 3-month-old, healthy females. The patients were healthy volunteers undergoing laparoscopy for pain, infertility or cholecystectomy. Both pigs and human volunteers underwent operative laparoscopic use of the ABC for hemostasis and selected tissue electrocoagulation using a prototype 10-mm laparoscopic probe. The safety of the ABC was evaluated in the pigs by continuously monitoring heart rate, oxygen saturation and end-tidal CO2. Patients had similar clinical monitoring during operative laparoscopy, with observation of tissue effects of the ABC for hemostasis and tissue electrocoagulation. Laparoscopic use of the ABC in animals and patients produced no observable anesthetic changes, with both pigs and patients recovering normally. The ABC allowed smokeless, hemostatic tissue electrocoagulation, with a rapid non-touching technique easy to apply laparoscopically. We conclude that the ABC can safely be used laparoscopically with excellent hemostasis and effective controlled tissue electrocoagulation. The lack of smoke and the non-touching technique for delivery allow rapid laparoscopic application. The prototype 10-mm delivery probe is cumbersome, and the argon gas flow rate of 4 L/min with firing requires constant venting of the peritoneum with close monitoring of intraperitoneal pressures. PMID- 8445603 TI - Gonadotropin releasing hormone agonist for chronic anovulatory uterine bleeding and severe anemia. AB - Twenty-three women with chronic heavy anovulatory uterine bleeding and severe iron-deficiency anemia received six months' treatment with goserelin, a gonadotropin releasing hormone agonist, administered as a monthly subcutaneous depot. After two months of treatment, all patients were amenorrheic and subsequent spotting was reported on only nine occasions. Laboratory results showed the following values: mean hemoglobin before treatment, 7.9 g/dL-13.8 g/dL at six months (+75%); mean hematocrit, 26.3%-41.6% (+58); mean serum iron, 19.8 micrograms/dL-63.3 micrograms/dL (+134%) and mean serum ferritin, 6.2 ng/mL-35.3 ng/mL (+469%). The endometrial hyperplasia observed in 11 subjects showed regression at follow-up suction biopsy. Gonadotropin releasing hormone agonists administered in a depot formulation for a few months in highly selected patients with severe anemia associated with heavy anovulatory uterine bleeding are practical, safe and effective, may avoid blood transfusions and could be used as a first line of treatment. PMID- 8445604 TI - Ovarian surgery via pelviscopy. AB - A retrospective study of operative pelviscopy was undertaken at the Department of Obstetrics and Gynecology at the Christian-Albrechts-University of Kiel to review the spectrum of ovarian surgery performed from 1987 to 1989. The purpose of this study was to assess the scope of surgery (cystectomies, ovariolysis, ovarian biopsy and cyst puncture), and to identify any advantages or disadvantages associated with the procedure. PMID- 8445605 TI - Assessment of fetal lung maturity by fluorescence polarization in high-risk pregnancies. AB - Although the validity of amniotic fluid fluorescence polarization (FPOL) has been documented in normal pregnancies, data are lacking on the predictive value of this method in high-risk pregnancies where biochemical maturation of the fetal lung may be altered. In this study, amniotic fluid was obtained from 86 women with pregnancies complicated by insulin-dependent diabetes (42), twin gestation (22), Rh sensitization (13) and known fetal anomalies (9). In all groups, when FPOL was > .280 (immature), phosphatidylglycerol (PG) was always absent and lecithin and sphingomyelin ratio (L/S) was < 2.5:1. When FPOL values were < .260 (mature), PG was always present and L/S was > 2.5 in 45/50 samples. When FPOL values ranged between .260-.280 (intermediate), L/S and PG values varied and were inconsistent. We conclude that FPOL assessment of fetal lung maturity in pregnancies complicated by diabetes, Rh sensitization, twin gestation and fetal anomalies is as accurate a procedure as is fetal lung maturity testing by L/S and PG. In addition, the testing procedure is quicker, more reproducible and, possibly, more reliable. PMID- 8445606 TI - Colonic surgery in gynecologic oncology. Risk factor analysis. AB - Colonic surgery is a critical part of gynecologic oncology care. A 12-year review of colonic surgery on a gynecologic oncology service was performed evaluating risk factors and their impact on postoperative morbidity. There were 124 procedures performed on 92 patients; 9 patients had no prior surgery, chemotherapy or radiation. Fifty-six percent of the patients were considered malnourished on the basis of a serum albumin level < 3.5 g/dL. The 124 procedures consisted of 57 colon resections with primary reanastomosis, 10 small bowel-colon bypass procedures and 57 colostomies. Of the 57 (67%) colostomy operations, 38 also had concomitant abdominal-pelvic procedures. There were 15 major bowel complications and 17 major systemic postoperative complications. Prior surgery and poor nutritional status significantly correlated with postoperative morbidity; however, prior radiation did not reveal an increased risk for postoperative complications. PMID- 8445607 TI - Prognosis and long-term follow-up of a twin after antenatal death of the co-twin. AB - It is generally believed that among twin pregnancies with one fetal loss prior to delivery, the surviving twin has an increased rate of perinatal mortality and childhood morbidity (cerebral palsy and mental retardation). By using data from the National Medical Birth Registry of Sweden between 1973 and 1983, we identified 206 gestations with the death of at least one twin (in 36 pregnancies both twins died) prior to delivery. The original medical records were retrieved for study. The presence of childhood morbidity for 65 of 129 surviving (8 years of age or older) twins born between 1973 and 1980 was evaluated by a questionnaire sent to rehabilitation centers for disabled children, as well as to offices for the Provision of Care for the Mentally Retarded. Perinatal mortality for a twin after the antenatal death of the co-twin was considerable. Fifty percent of survivors died before 34 weeks' gestation, and 18.7% thereafter. At follow-up, 8 years or more after birth, three twins (4.6%) were handicapped. Our results indicate the need for careful monitoring of the surviving twin fetus after one twin has succumbed prenatally. PMID- 8445608 TI - Comparison of cytobrush and cotton swab for Papanicolaou smears in pregnancy. AB - Papanicolaou smears obtained using cytobrush or cotton swabs were compared in 222 pregnant women. There were no complications attributable to the cytobrush. Endocervical cell yields obtained with the brush were 70.9% compared to 41.9% with the swab (P = .0001). There was no difference between use of the swab and the brush in the prevalence of dysplasia (19 cases) nor was there any difference in the prevalence of dysplasia in the smears that contained endocervical and/or metaplastic cells (17/181 = 8.6%) compared to those not containing these cell types (2/24 = 8.3%). This study suggests that use of the cytobrush in pregnancy warrants further study because of the frequency with which smears are reported as inadequate because they lack endocervical and/or metaplastic cells. PMID- 8445609 TI - Human chorionic gonadotropin pattern in maternal circulation. Amniotic fluid and fetal circulation in late pregnancy. AB - This study had two purposes. One was to investigate the placental gradients and the relationship of human chorionic gonadotropin (hCG) concentrations in maternal serum (MS), amniotic fluid (AF) and fetal serum (FS). The other was to study the fetal sex effect. This study included 93 patients with normal singleton term pregnancies. AF samples contaminated with blood were excluded. Fetuses did not have any abnormalities. We measured hCG by double antibody beta hCG radioimmunoassay. We found that there were conspicuous hCG slopes in MS, AF and FS levels. The hCG level in MS was 12.9 +/- 1.3 IU/mL (mean +/- SE, n = 93). It was much higher than levels in AF or FS. AF (0.461 +/- 0.053 IU/mL, n = 25) also had higher hCG level than FS (0.038 +/- 0.0056 IU/mL, n = 93). The hCG concentrations in AF and FS were highly correlated with those in corresponding MS (P < .001 and P < .05, respectively). The concentrations in AF were also positively correlated with those in corresponding FS (P < .05). The mean of MS/AF ratios for hCG was 413.6 +/- 23.4 (+/- SE); of MS/FS, it was 37.8 +/- 9.2; of AF/FS, it was 15.3 +/- 2.6. At late pregnancy, higher hCG levels of MS, AF or FS may result in female fetuses than in male fetuses. The results revealed that there were hCG concentration gradients on both placental and fetal membranes. It also implied that hCG levels in AF may decline as gestation ages advance. For biochemical studies in FS, using pure cord venous blood may have more consistent results than using mixed blood.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8445610 TI - Primary ovarian pregnancy. A case report. AB - Primary ovarian pregnancy is a rare entity that is increasing in incidence. It is difficult to diagnose clinically and even intraoperatively. Conservative surgical management is advocated in young patients with good prognosis for future fertility. PMID- 8445611 TI - Pelvic actinomycosis presenting as a primary retroperitoneal mass. A case report. PMID- 8445612 TI - Detailed genetic mapping of the von Hippel-Lindau disease tumour suppressor gene. AB - Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited familial cancer syndrome characterised by a predisposition to the development of retinal, cerebellar, and spinal haemangioblastomas, renal cell carcinoma, and phaeochromocytoma. The gene for VHL disease has been mapped to chromosome 3p25 p26 and flanking markers identified. We report the detailed genetic mapping of the VHL disease locus in 38 families. Significant linkage was detected between VHL disease and D3S601 (Zmax = 18.86 at theta = 0.0, CI 0.0-0.025), D3S18 (Zmax = 11.42 at theta = 0.03, CI 0.005-0.08), RAF1 (Zmax = 11.02 at theta = 0.04, CI 0.007-0.01), and D3S1250 (Zmax = 4.73 at theta = 0.05, CI 0.005-0.15). Multipoint linkage analysis mapped the VHL disease locus between D3S1250 and D3S18 close to D3S601. There was no evidence of locus heterogeneity. This study has (1) confirmed the tight linkage between VHL disease and D3S601, (2) identified D3S1250 as the first marker telomeric to RAF1 which maps centromeric to the VHL disease gene, and (3) narrowed the target region for isolation of the VHL disease gene by positional cloning techniques to a 4 cM interval between D3S1250 and D3S18. These findings will improve the clinical management of families with VHL disease by improving the accuracy of presymptomatic diagnosis using linked DNA markers, and will enhance progress towards isolating the VHL disease gene. PMID- 8445613 TI - Emery-Dreifuss muscular dystrophy: linkage to markers in distal Xq28. AB - Emery-Dreifuss muscular dystrophy (EMD) is characterised by (1) early contractures of the Achilles tendons, elbows, and postcervical muscles, (2) slowly progressive muscle wasting and weakness with a predominantly humeroperoneal distribution in the early stages, and (3) cardiomyopathy with conduction defects and risk of sudden death. Inheritance is usually X linked recessive but can be autosomal dominant. Family linkage studies have mapped X linked EMD to the distal long arm of the X chromosome but precise genetic localisation has been hampered by the rarity of this condition. We report three new families with X linked Emery-Dreifuss muscular dystrophy studied with DNA markers from Xq27-qter and three previously published families typed for additional markers. No recombination was observed with the red/green cone pigment locus, RGCP (lod score, Z = 2.46), the factor VIII coagulant gene locus, F8C (Z = 6.39), or with DXS115 (Z = 4.94). Two recombinants were observed which mapped EMD distal to DXS15 (DX13) and DXS52 (St14) respectively. Multipoint linkage analysis gave odds exceeding 200:1 for EMD being distal to these markers. A multipoint analysis incorporating published data gave the map cen-DXS304-9cM-DXS15-3cM-DXS52 2 cM-(RGCP,EMD)-3cM-F8C-2cM-DXS115 with odds of 120:1 in favour of a location for EMD between DXS52 and F8C as compared to the next best position distal to F8C. PMID- 8445614 TI - On the genetics of mandibular prognathism: analysis of large European noble families. AB - Mandibular prognathism is assumed to be a polygenic trait in the vast majority of cases. In a few families, this phenotype and perhaps a syndrome with a broader spectrum of facial anomalies seems to be determined by a single dominant gene of very low frequency (McKusick No *176700). The phenotype is known to have occurred independently in several European noble families. We constructed a pedigree comprising 13 of these families with 409 members in 23 generations in which mandibular prognathism has been segregating. Obviously, the presumed dominant gene is not fully penetrant in the heterozygous state. Pedigree analysis using the Elston-Stewart algorithm yields a maximum likelihood estimate (MLE) of p = 0.955 (SE 0.038) of the penetrance parameter. PMID- 8445615 TI - Two new mutations in a late infantile Tay-Sachs patient are both in exon 1 of the beta-hexosaminidase alpha subunit gene. AB - We have identified two new point mutations in the beta-hexosaminidase alpha subunit (HEX A) gene in a non-Jewish Tay-Sachs disease patient with an unusual late infantile onset disease phenotype. The patient was a compound heterozygote with each allele of the HEX A gene containing a different mutation in exon 1. One of these is a T to C transition in the initiation codon, expected to produce no alpha subunit and therefore a classical infantile phenotype. The unusual clinical aspects and later onset in the patient must therefore be a result of residual hexosaminidase A activity associated with a mutant alpha subunit containing the second mutation, substitution of serine for proline at amino acid 25 owing to a C to T change at nucleotide 73. Western blotting and DE-52 ion exchange chromatography have been used to examine the behaviour of this mutant alpha subunit. PMID- 8445616 TI - Mutation analysis in Turkish phenylketonuria patients. AB - Forty-four classical PKU patients have been screened for various mutations. The newly identified IVS 10 splicing mutation was found in 32% of the mutant alleles and comprises 74.5% of the mutations that could be typed: 261arg-gln (6.8%), 158arg-gly (2.3%), 252arg-trp (1.1%), 280glu-lys (-), and 272gly-stop (-) were the other mutations that were screened. PMID- 8445617 TI - Cosegregation of schizophrenia with Becker muscular dystrophy: susceptibility locus for schizophrenia at Xp21 or an effect of the dystrophin gene in the brain? AB - A family is reported in which four of five adult patients with Becker muscular dystrophy (BMD) also have schizophrenia or related spectrum disorders. Although the estimated lod scores are not sufficient to conclude the existence of linkage between BMD and schizophrenia, it is suggested that there may be an association between these two disorders. Two alternative hypotheses are proposed to explain such an association: (1) the existence of a susceptibility locus for schizophrenia and spectrum disorders on the short arm of the X chromosome at Xp21; (2) that these psychiatric disorders may result from an abnormality in the expression of the dystrophin gene in the brain. PMID- 8445619 TI - Molecular diagnosis of some common genetic diseases in Russia and the former USSR: present and future. AB - The current state of molecular diagnosis of some common genetic diseases, including cystic fibrosis, Duchenne muscular dystrophy, haemophilia A and B, phenylketonuria, and thalassaemia, in Russia and elsewhere in the former USSR is reviewed. Data on carrier detection and prenatal diagnosis are presented and some objective problems and obstacles hampering efficient molecular diagnosis in Russia are discussed. The necessity for molecular diagnosis of some other inherited diseases (for example, von Willebrand's disease, Martin-Bell syndrome, polycystic kidney disease, Huntington's disease, and myotonic dystrophy) is stressed. The need for establishing new diagnostic centres dealing with the most common diseases, as well as rare genetic diseases, is substantiated. Perspectives on the implementation of new molecular methods and new technical approaches (preimplantation embryo diagnosis, fetal cells selected from maternal blood) are briefly outlined. PMID- 8445618 TI - A family showing no evidence of linkage between the ataxia telangiectasia gene and chromosome 11q22-23. AB - We have studied an inbred family in which two cousins presented with the same clinical features of ataxia telangiectasia (AT). Both patients are still ambulatory at ages 25 and 20. Cellular features of both patients are typical of AT and include increased radiosensitivity and an increased level of spontaneously occurring chromosome aberrations in peripheral blood lymphocytes. Linkage studies and haplotype analysis show no clear evidence that the gene for AT in this family is on chromosome 11q22-23. As previously reported AT families from complementation groups AB, C, and D have all shown linkage to this region of 11q22-23. Our study is of importance in suggesting additional locus heterogeneity. PMID- 8445620 TI - The specialty of clinical genetics: European Society of Human Genetics survey. PMID- 8445621 TI - Rapid and efficient PCR/StyI test for identification of common mutation R408W in phenylketonuria patients. PMID- 8445622 TI - A lethal skeletal dysplasia with generalised sclerosis and advanced skeletal maturation: Blomstrand chondrodysplasia? AB - The clinical and radiological features in a baby thought to have Blomstrand chondrodysplasia are presented. The hallmarks of this rare lethal disorder are an increase in bone density and advanced skeletal maturation. A high incidence of parental consanguinity is consistent with autosomal recessive inheritance. PMID- 8445623 TI - Brachymorphism-onychodysplasia-dysphalangism syndrome. AB - Three unrelated children are reported with intrauterine proportionate growth retardation and facial dysmorphism (broad nose, flat malar area, large mouth, pointed chin), microcephaly, hypo/aplasia of the terminal fifth digits, and (sub)normal intelligence. Radiological findings include hypo/aplasia or fusion of the distal phalanges of the fifth finger and toe, brachymesophalangism V, and nail dysplasia or aplasia. One child had cystic adenomatoid disease of the lung. The pattern of anomalies presented by these children closely resembles a syndrome incompletely delineated in 1971 by Senior in six children, which has often been considered to be a mild form of Coffin-Siris syndrome. We suggest that this is an independent entity (BOD syndrome). The aetiology is still unknown. Differential diagnosis and nosological difficulties are discussed. PMID- 8445624 TI - Rapid diagnosis of infantile spinal muscular atrophy by direct amplification of amniocyte and CVS DNA. PMID- 8445625 TI - Complex chromosome rearrangement with ankyloblepharon filiforme adnatum. AB - A Caucasian boy with a de novo complex chromosome rearrangement owing to six chromosome breaks was small for gestation with microcephaly, complex heart defect, hypotonia, left auricular pit, simian creases, and ankyloblepharon filiforme adnatum. The rearrangement included two translocation, t(15;21) (q22;q22) and t(3;11)(q21;q11), with the derivative 3 showing in addition pericentric inversion (p11q11) and interstitial deletion (q11q21). Based on parental satellite polymorphisms of chromosomes 15 and 21, the paternal gamete appeared to be the source of the chromosome rearrangement. There was no evidence of mitotic chromosome instability. A review of 36 reported patients with complex chromosome rearrangements secondary to more than four breaks indicates that complex chromosome rearrangements are compatible with gamete survival, zygote formation, and postnatal life. The latter is usually compromised by structural defects, growth retardation, and often mental retardation. PMID- 8445626 TI - Chromosome 20 long arm deletion in an elderly malformed man. AB - A 46,XY/46,XY,del(20)(q13-->q13.33) mosaicism was identified in a 68 year old man who had mild mental retardation and severe malformation of the limbs. The clinical findings of the patient are compared to those of the very few cases of 20q deletion published to date. PMID- 8445627 TI - Hydrocephalus in Hajdu-Cheney syndrome. PMID- 8445628 TI - The fragile X syndrome: no evidence for any recent mutations. AB - Fragile X (fra(X)) syndrome, the most common form of familial mental retardation, is caused by heritable unstable DNA composed of CGG repeats. As reproductive fitness of fra(X) patients is severely compromised, a high mutation rate has been proposed to explain the high prevalence. However, we have been unable to show any new mutation for 84 probands referred to us to date. We show here the same fra(X) gene in five fra(X) probands with common ancestors married in 1747. The lack of new fra(X) mutations implies that there must be many more fra(X) gene carriers in the population than previously realised. As it is now possible to detect asymptomatic fra(X) gene carriers by DNA analysis, extended family studies for any new proband are recommended. A family illustrating the importance of fra(X) carriership determination is reported. PMID- 8445629 TI - Identification of the FRAXE fragile site in two families ascertained for X linked mental retardation. AB - Chromosome fragility in two families not exhibiting amplification of the CGG trinucleotide associated with the fragile X site has been examined. Fluorescence in situ hybridisation with cosmid DNA from loci immediately flanking FRAXA and other distal loci have confirmed that cytogenetic fragility in these subjects is the result of expression of a new folate sensitive fragile X site, FRAXE. PMID- 8445630 TI - A method for spatio-temporal (4-D) data representation in confocal microscopy: application to neuroanatomical plasticity. AB - This paper describes a new method for data representation and visualization in four dimensions (three dimensions plus time). Sequential volumes, exhibiting morphological activity, are acquired non-invasively with a confocal scanning laser microscope, where each data set corresponds to a time sample. A pipelined processing includes packing of volumes and specific volume rendering techniques. Subsequent processing in HIS (hue, intensity, saturation)l colour space combines functional, packed images with shaded three-dimensional views. As a result, even subtle changes in morphology become visible and computational time is saved. Experimental findings obtained from investigations of synaptic plasticity in cultured retinal tissue are reported. PMID- 8445631 TI - A synchroton X-ray study of the changes occurring in the corneal stroma during processing for electron microscopy. AB - Using a high-intensity synchroton X-ray source, the structural changes occurring in the corneal stroma were monitored during each stage of several different processing runs for the transmission electron microscope (TEM) and scanning electron microscope (SEM). The parameters studied were interfibrillar spacing, intermolecular spacing, D-periodicity and fibril diameter. The processing schedule that produced the least changes in spacings for TEM specimens involved extended fixation in glutaraldehyde followed by low-temperature embedding in Lowicryl K4M resin. However, interfibrillar material was better preserved after embedding in LR White resin or Nanoplast. Almost every processing stage for electron microscopy produced significant changes in one or more structural parameters in the cornea. Glutaraldehyde fixation significantly increased the intermolecular spacings, while resin infiltration and resin polymerization each resulted in shrinkage of all the spacings monitored. Critical-point drying for SEM specimens resulted in considerable shrinkage in all three spacings, but was still preferable to air drying, which caused reduction in the order of the fibril packing, resulting in loss of the interfibrillar X-ray pattern. Perhaps the most drastic effect was caused by post-fixation in osmium tetroxide, which resulted in loss of the intermolecular pattern, and also increased the amount of shrinkage in the interfibrillar spacings and the D-periodicity which occurred during later stages of processing. PMID- 8445632 TI - Glucose alone does not completely hydrate bacteriorhodopsin in glucose-embedded purple membrane. AB - Glucose embedding is a simple and highly effective method for preparing biological macromolecules for high-resolution electron microscopy. The investigation of conditions that can trap the M-state intermediate in the bacteriorhodopsin (bR) photocycle has revealed, however, that when glucose embedded bR is prepared at ambient humidity, it does not fully retain the capability to execute a proper photocycle. However, 'native' photocycle properties are returned after glucose-embedded samples are equilibrated at 81% relative humidity. Equilibration at relative humidities significantly higher than 81% causes glucose to dissolve in its own water of hydration, resulting in samples that may be too thick to be suitable for electron microscopy. The results obtained with bR indicate that caution should be taken with other biological specimens, and it cannot be assumed that glucose-embedded biological macromolecules retain completely their native, hydrated structure, even when high resolution electron diffraction patterns are obtained. Equilibration of such samples at high humidity may generally be a worthwhile precaution when using the glucose-embedding technique. PMID- 8445633 TI - A simple modification to the LKB 7800 series Knifemaker and a balanced-break method to prepare glass knives for cryosectioning. AB - A novel method of using the LKB 7800 series Knifemaker to produce glass knives using a balanced break is described. The method produces knives of sufficient quality to section aldehyde-fixed, sucrose-cryoprotected, frozen biological material in a cooled cryochamber of an ultramicrotome. The modifications to the Knifemaker are minimal and, if required, the machine can be returned easily to its normal state after use. PMID- 8445634 TI - Refined 1.6 A resolution crystal structure of the complex formed between porcine beta-trypsin and MCTI-A, a trypsin inhibitor of the squash family. Detailed comparison with bovine beta-trypsin and its complex. AB - The crystal structure of the complex formed by porcine beta-trypsin with the MCTI A inhibitor (Momordica charantia, Linn. Cucurbitaceae) has been determined at 1.6 A resolution using the molecular replacement method. The sequence of MCTI-A was determined by recognizing the electron density, and shows that MCTI-A is a member of the squash family of trypsin inhibitors. We report the first high-resolution structure of porcine beta-trypsin. Detailed comparisons have been made on the overall structure, solvent structure and active-site geometries between this complex and bovine beta-trypsin and its complexes. On the basis of our results, we discuss the interaction patterns between inhibitor and trypsin. Unlike other complex structures formed by bovine trypsin with inhibitors, no out-of-plane distortion around the inhibitor's scissible peptide was observed. The role of the trypsin catalytic triad is also discussed on the basis of this structure. PMID- 8445635 TI - Three-dimensional structure of the lipoyl domain from Bacillus stearothermophilus pyruvate dehydrogenase multienzyme complex. AB - The structure of the lipoyl domain from the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus has been determined by means of nuclear magnetic resonance spectroscopy. A total of 452 nuclear Overhauser effect distance constraints and 76 dihedral angle restraints were employed as the input for the structure calculations, which were performed using a hybrid distance geometry-simulated annealing strategy and the programs DISGEO and X-PLOR. The overall structure of the lipoyl domain (residues 1 to 79 of the dihydrolipoamide acetyltransferase polypeptide chain) is that of a flattened eight-stranded beta barrel folded around a core of well-defined hydrophobic residues. The lipoylation site, lysine 42, is located in the middle of a beta-turn, and the N and C terminal residues of the domain are close together in adjacent beta-strands at the opposite end of the molecule. The polypeptide backbone exhibits a 2-fold axis of quasi-symmetry, with the C alpha atoms of residues 15 to 39 and 52 to 76 being almost superimposable on those of residues 52 to 76 and 15 to 39, respectively (root-mean-square deviation = 1.48 A). The amino acid residues at key positions in the structure are conserved among all the reported primary structures of lipoyl domains, suggesting that the domains all fold in a similar way. PMID- 8445636 TI - Empirical and structural models for insertions and deletions in the divergent evolution of proteins. AB - The exhaustive matching of the protein sequence database makes possible a broadly based study of insertions and deletions (indels) during divergent evolution. In this study, the probability of a gap in an alignment of a pair of homologous protein sequences was found to increase with the evolutionary distance measured in PAM units (number of accepted point mutations per 100 amino acid residues). A relationship between the average number of amino acid residues between indels and evolutionary distance suggests that a unit 30 to 40 amino acid residues in length remains, on average, undisrupted by indels during divergent evolution. Further, the probability of a gap was found to be inversely proportional to gap length raised to the 1.7 power. This empirical law fits closely over the entire range of gap lengths examined. Gap length distribution is largely independent of evolutionary distance. These results rule out the widely used linear gap penalty as a satisfactory formula for scoring gaps when constructing alignments. Further, the observed gap length distribution can be explained by a simple model of selective pressures governing the acceptance of indels during divergent evolution. Finally, this model provides theoretical support for using indels as part of "parsing algorithms", important in the de novo prediction of the folded structure of proteins from the sequence data. PMID- 8445637 TI - Three-dimensional structure of the glutathione synthetase from Escherichia coli B at 2.0 A resolution. AB - Glutathione synthetase (gamma-L-glutamyl-L-cysteine: glycine ligase (ADP-forming) EC 6.3.2.3: GSHase) catalyzes the synthesis of glutathione from gamma-L-glutamyl L-cysteine and Gly in the presence of ATP. The enzyme from Escherichia coli is a tetramer with four identical subunits of 316 amino acid residues. The crystal structure of the enzyme has been determined by isomorphous replacement and refined to a 2.0 A resolution. Two regions, Gly164 to Gly167 and Ile226 to Arg241, are invisible on the electron density map. The refined model of the subunit includes 296 amino acid residues and 107 solvent molecules. The crystallographic R-factor is 18.6% for 17.914 reflections with F > 3 sigma between 6.0 A and 2.0 A. The structure consists of three domains: the N-terminal, central, and C-terminal domains. In the tetrameric molecule, two subunits that are in close contact form a tight dimer, two tight dimers forming a tetramer with two solvent regions. The ATP molecule is located in the cleft between the central and C-terminal domains. The ATP binding site is surrounded by two sets of the structural motif that belong to those respective domains. Each motif consists of an anti-parallel beta-sheet and a glycine-rich loop. PMID- 8445638 TI - Nicotinic acetylcholine receptor at 9 A resolution. AB - The nicotinic acetylcholine receptor is a cation-selective, ligand-gated ion channel, involved in signal transmission at the chemical synapse. This paper reports the three-dimensional appearance of the channel in the closed conformation, at 9 A resolution. The structure was determined by electron microscopy of tubular crystals of Torpedo postsynaptic membranes embedded in amorphous ice. The analysis was carried out by averaging data from separate images, using helical diffraction methods. The images were recorded over a wide range of defocus (7000 to 18,800 A) so that all spacings in the object were well sampled. Tubes of only one kind ((-16.6) helical family) were processed, so that the Fourier terms could be averaged directly in reciprocal space. The three dimensional map, obtained from 26 images, resolves some elements of secondary structure within the five protein subunits. In the synaptic part of each subunit, about 30 A from the bilayer surface, there is a group of three rods that are oriented predominantly perpendicular to the plane of the bilayer and twist around each other as in a left-handed coil. These rods presumably are alpha-helices. Two of them line the entrance to the channel, and the third is on the outside. The distinctive appearance of the alpha subunits in this region suggests that the rods may be involved in forming the binding pocket for acetylcholine. In the bilayer-spanning part of each subunit there is only one rod clearly visible, which forms the wall lining the pore, and so is assumed to be the transmembrane helix, M2. This rod does not form a straight path through the lipid bilayer, but bends, or kinks, near its mid-point, where it is closest to the axis of the pore, and tilts radially outwards on either side. It is flanked on the lipid-facing sides by a continuous rim of density, which seems likely to be composed of beta sheet. A tentative alignment is made between the three-dimensional densities and the sequence of M2, based on correlation of the appearance of the rods with a special pattern of amino acid residues in the sequence. This alignment places the charged groups at the ends of M2 symmetrically on either side of the bilayer, and a highly conserved leucine residue (Leu251 of the alpha subunit) at the level of the kink.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8445639 TI - Crystals of phospholipase A2 inhibitor. The non-toxic component of vipoxin from the venom of Bulgarian viper (Vipera ammodytes). AB - Phospholipase A2 inhibitor, the non-toxic, acidic component of vipoxin from the venom of Bulgarian viper (Vipera ammodytes), has been crystallized. The tetragonal crystals obtained, exhibit the symmetry of space group P4(1)22 (or 4(3)22) with unit cell dimensions a = b = 59.9 A; c = 141.1 A; alpha = beta = gamma = 90 degrees. For two molecules per asymmetric unit, this would give Vm = 2.3 A3/Da, indicating normal packing. The crystals diffract to 2.5 A and a native data set to 3.2 A resolution has been collected. PMID- 8445640 TI - Crystallization and preliminary X-ray diffraction studies of recombinant human interleukin-5. AB - Recombinant human interleukin-5 (rhIL-5) has been crystallized by the hanging drop vapor diffusion method using 0.1 M-Tris.HCl buffer (pH 8.5) containing 0.2 to 0.25 M-sodium acetate and 26 to 30% PEG 4000 at 22 degrees C. The parallel piped crystals belong to the space group C2 with unit cell dimensions of a = 122.1 A, b = 36.11 A, c = 56.42 A, beta = 98.59 degrees. They diffract to at least 2.0 A resolution on a rotating anode X-ray source. The molecular mass weight of the protein and the volume of the unit cell suggest that the asymmetric unit contains one intermolecular disulfide-bonded homodimer. PMID- 8445641 TI - Crystallization and preliminary crystallographic data for formyltetrahydrofolate synthetase from Clostridium thermoaceticum. AB - Formyltetrahydrofolate synthetase from Clostridium thermoaceticum has been crystallized using the hanging-drop method from ammonium sulphate and PEG solutions. Crystals are trigonal, the space group is R32, a = 163 A, c = 259 A. A 4.2 A resolution data set has been collected. Analysis of the data using the self rotation function shows that tetramers have approximate 222 symmetry and are positioned on a crystallographic 2-fold axis. PMID- 8445642 TI - Crystallization and preliminary X-ray crystallographic analysis of the protease inhibitor ecotin. AB - Ecotin, a novel serine protease inhibitor isolated from Escherichia coli, has been crystallized using polyethylene glycol 1500 as the precipitating agent. The crystals belong to the orthorhombic space group P2(1)2(1)2(1), with unit cell parameters of a = 39.22 A, b = 84.86 A, and c = 98.74 A. The asymmetric unit contains one dimeric molecule of ecotin, with a crystal volume per protein mass (Vm) of 2.55 A3/Da and a solvent content of 51.8% by volume. The crystals diffract to at least 2.2 A using a conventional X-ray source, and X-ray data have been collected to 2.7 A Bragg spacing from a native crystal. PMID- 8445643 TI - Formation in vivo, purification and crystallization of a complex of the gamma and epsilon subunits of the F0F1-ATPase of Escherichia coli. AB - A complex comprising the epsilon subunit of Escherichia coli F1-ATPase (ECF1 ATPase) and a glutathione-S-transferase gamma subunit (of ECF1-ATPase) fusion protein was formed in vivo and purified from cell extracts by binding to glutathione-agarose beads. The glutathione-S-transferase was released from the complex by digestion with thrombin and the gamma/epsilon complex purified by cation-exchange chromatography. Crystals of the complex were grown by vapour diffusion using PEG8000 as precipitant. The crystals are orthorhombic, space group P2(1)2(1)2 with a = 161.9 A, b = 44.1 A and c = 63.4 A. The volume of the asymmetric unit is consistent with the presence of a complex of one gamma subunit and one epsilon subunit. PMID- 8445644 TI - Crystallization and preliminary X-ray analysis of a truncated tissue metalloproteinase inhibitor delta 128-194 TIMP-2. AB - Crystals of an active truncated form of a human tissue metallproteinase inhibitor (delta 128-194 TIMP-2), a protein implicated in a number of diseases of the connective tissues, have been grown in a form suitable for study by X-ray diffraction analysis. Crystals grow using polyethylene glycol 600 as a precipitant and are in space group P2(1)2(1)2, with cell dimensions a = 75.28 A, b = 100.77 A, c = 31.45 A. The asymmetric unit appears to contain two molecules of delta TIMP-2 with a Vm value of 2.3 A3/dalton. The crystals diffract to Bragg spacings beyond 2.5 A. Native data to 3.2 A have been collected and a search for heavy-metal derivatives is in progress. PMID- 8445645 TI - A superfamily of ATPases with diverse functions containing either classical or deviant ATP-binding motif. AB - A superfamily of ATPases is described with its members sharing three distinct conserved amino acid sequence motifs. The superfamily includes numerous proteins involved in active partitioning of bacterial plasmids and chromosomes, nitrogenase iron proteins (nifH gene products), the anion pump ATPase ArsA, and VirC1 proteins encoded by Agrobacterium Ti plasmids and apparently involved in formation of single-stranded plasmid DNA. A database search identified partial sequences of genes encoding putative human and archaebacterial chromosome partitioning ATPases, suggesting that these proteins fulfil a universal function in cell division. The proteins belonging to this superfamily show the transition from the classical fingerprint of the A type purine NTP-binding motif, GXXGXGK[ST], to a significantly modified signature, KGGXXK[ST], with the apparent preservation of the loop conformation typical of this motif. It is speculated that the ancestral form of the A motif might have comprised a loop rich in Gly residues, GXGGXGK[ST], resembling that in NifH proteins and ArsA. Some of the Gly residues might have been differentially substituted in various evolutionary lineages of NTPases. The functional diversity of the proteins of this ATPase superfamily is comparable with the range of functions described previously for the superfamily of "UvrA-related" ATPases. PMID- 8445646 TI - Expression of the human placental folate receptor transcript is regulated in human tissues. Organization and full nucleotide sequence of the gene. AB - The primary structures of the human KB cell (FR-KB1) folate receptor (FR) and of a human placental (FR-P2) FR, proteins important in cellular accumulation of folates, have been deduced from cDNA sequences. Herein, we report a novel human FR cDNA (FR-P3) isolated from a placental library and the chromosomal organization of the human FR-P3 gene. Compared to the FR-P2 cDNA, the composite 1084 base-pair (bp) FR-P3 cDNA is homologous, but contains a unique 5' terminus and sequence differences within the open reading frame (ORF) and at the exon I-II junction. Polymerase chain reaction and RNase protection assays demonstrate that the FR-P3 cDNA represents the major transcript, and suggest that the FR-P2 cDNA is encoded by an independent FR gene. The nucleotide sequences of two non overlapping human genomic clones contain the FR-P3 gene, which spans 5148 bp, is composed of five exons, and is polymorphic relative to 5' restriction sites. The transcript size (1084 bp) predicted from structural analysis of the FR-P3 gene correlates with the size (1100 bp) determined by Northern blots. Based on RNase protection assays, both FR-P3 and FR-KB1 transcripts are expressed in human fetal and adult tissues, and the abundance of each transcript varies among the tissues studied. These results indicate that the FR transcripts are products of independent, conserved genes; that neither FR gene is preferentially expressed during fetal development; and that specific FR transcripts are differentially expressed in human tissues, suggesting that transcription of each FR gene is regulated independently. The isolation of the FR-P3 gene will permit functional analysis of the cis and trans regulatory elements of the FR-P3 gene and the mechanisms involved in tissue-specific FR gene expression. PMID- 8445647 TI - Hierarchy of base-pair preference in the binding domain of the bacteriophage T7 promoter. AB - The activity of bacteriophage T7 RNA polymerase (RNAP) at a collection of T7 promoter mutants having all possible single base-pair substitutions in the region from -15 to -6 was determined by transcription in vitro, thus establishing a hierarchy of base-pair preference at each position. The tolerance of the RNAP for base-pair substitutions is not uniform across the binding domain. Under stringent conditions (20 mM-MgCl2), T7 RNAP is highly permissive for all base-pair substitutions at -13 and -12. The RNAP is partially permissive at -15, -14, -11, 10 and -6, and exhibits a clear pattern of base-pair preference at these positions. The RNAP is non-permissive for substitutions at -9 to -7, and will accept only the consensus base-pairs at these positions. Under lower stringency conditions (8 mM-MgCl2, or additionally in the presence of dimethylsulfoxide) a decrease in specificity is observed at most positions except -9. Analysis of these data suggests potential contacts that may be important for promoter function. PMID- 8445648 TI - Crossed-stranded DNA structures for investigating the molecular dynamics of the Holliday junction. AB - We have developed a simple and rapid procedure for the synthesis and isolation of figure-eight DNA molecules (figure-8s) beginning with phagemid vectors. The figure-8 molecules generated contain a Holliday junction within 2.9 kb (1 kb = 10(3) bases or base-pairs) of continuous homology connecting the two monomer duplexes. The structure of these molecules was verified by restriction endonuclease analysis, two-dimensional agarose gel electrophoresis, and electron microscopy. Digestion of the figure-8 molecules with a restriction enzyme that cleaves only within the region of DNA sequence homology converted them to X-forms that could dissociate to yield linear monomers. The X-form molecules were stable under physiological conditions, a finding contradicting the notion that spontaneous branch migration is fast. PMID- 8445649 TI - Specificity of the Mnt protein. Independent effects of mutations at different positions in the operator. AB - The relative binding affinities of Mnt protein are determined for each possible base-pair at position 15 of the operator sequence, and for all combinations of G.C base-pairs at positions 15 and 17. The partitioning of each operator sequence is determined quantitatively with restriction enzymes. At position 15, the wild type G.C base-pair provides the highest binding affinity but, unlike position 17, the primary distinction is between purine and pyrimidine bases on the top strand. The information content at position 15 is only about 0.16 bit. In comparison with previous measurements at position 17, it is determined that the interactions of the Mnt protein with positions 15 and 17 are independent, i.e. the specific binding energies for the two positions are additive. The relative binding affinities at position 17 are also determined in the background of a G to T mutation at position 5, the position equivalent to 17 on the other half of the symmetric operator. The relative affinities at position 17 are independent of whether position 5 is wild-type or mutant. PMID- 8445650 TI - Structure of nucleosomal DNA at high salt concentration as probed by hydroxyl radical. AB - The structure of a 146 base-pair nucleosomal DNA has been probed using hydroxyl radical cleavage in buffers containing NaCl concentrations ranging from 80 mM to 800 mM. The highest salt concentrations used here are close to those required to dissociate core histone H2A and H2B from nucleosomal DNA. Nonetheless, the cleavage pattern of the DNA is unchanged over the tenfold salt concentration range, retaining the approximately 10.0 base-pairs per turn helical periodicity in the flanking regions and approximately 10.7 base-pairs per turn periodicity in the central dyad region that is characteristic of nucleosomal DNA. The rotational frame of the DNA is similarly unaffected by salt. These results support the contention that the differential free energy of bending of DNA around the nucleosome is independent of salt concentration. PMID- 8445651 TI - Significant dispersed recurrent DNA sequences in the Escherichia coli genome. Several new groups. AB - New computer and statistical methods were used to determine significant direct and inverted repeats in the Escherichia coli contig sequence collection of aggregate 1.6 x 10(6) base-pairs. Eight groups of mostly new structural repeat identities were uncovered. Apart from the high statistical significance of these repeat sequences, there are suggestive relationships of the group matches in terms of neighboring genes, of genomic distributions, of their texts, and of their potentials for secondary structure. Four of these groups are relatively numerous, 11 to 26 members, one is in coding sequences and three are in non coding. The coding group consists of the ATP-activated transmembrane component of a typical high-affinity protein-binding transport system. One of the non-coding groups consists of a special rho-independent transcription termination signal closely following an operon. The gene neighbors of this group often appear to be involved in some way in processing RNA or DNA. A second non-coding group has, for one or both neighboring genes, a component of a system responding to stress or starvation for some nutrient. PMID- 8445652 TI - Duck lactate dehydrogenase B/epsilon-crystallin gene. Lens recruitment of a GC promoter. AB - In duck the single copy lactate dehydrogenase B (LDH-B) gene also encodes an abundant lens protein, epsilon-crystallin. The LDH-B/epsilon-crystallin gene consists of eight exons, of which the first is non-coding. The promoter region lacks a TATA box, is very GC-rich and contains multiple consensus Sp1 binding sites. The gene has two discrete transcription start sites located 28 base-pairs apart. Both sites are used about equally in heart tissue, while transcription from the downstream start site predominates in the lens. For maximal promoter activity in lens or heart, sequences from the first intron are required. The enhancer(s) in this intron is promoter specific as it could not activate the tk promoter. Studies at the RNA level show that the overexpression of the LDH B/epsilon-crystallin gene in the lens is regulated at the transcriptional level, yet no tissue-specific regulatory elements could be detected in a region spanning from -1.9 kb (1 kb = 10(3) bases or base-pairs) up to the translation initiation site in the second exon. The basis for the differential expression of the LDH B/epsilon-crystallin gene in duck heart and lens is the usage of the downstream transcription initiation site. However, our results do not allow a distinction between activation of the downstream transcription start site in the lens or repression of the use of this site in heart. PMID- 8445653 TI - Mammalian heterogeneous ribonucleoprotein A1 and its constituent domains. Nucleic acid interaction, structural stability and self-association. AB - With a view toward further understanding the structure-function relationships of the eukaryotic heterogeneous ribonucleoprotein (hnRNP) A1, and in particular its multiplicity of nucleic acid-interactive domains, we have studied the nucleic acid binding properties of the globular N-domain (UP1) and sequence-repetitive, flexible C-domain, the thermal denaturation of UP1 and the concomitant effects of binding polynucleotide, and the self-associative properties of the full-length protein. Utilizing protein tryptophan fluorescence as a probe, polynucleotide binding was shown to stabilize UP1 against thermal unfolding. The denaturation profile of UP1-poly(thymidylic acid) complexes was biphasic, suggesting that unfolding of the two subdomains of UP1 can occur independently. This is in agreement with a previously proposed structure in which only one of the two UP1 subdomains binds the nucleic acid. The subdomains of UP1 can be prepared by controlled proteolysis of A1, further indicating that these two globular segments within A1 are connected by an exposed, flexible linkage. Circular dichroism measurements on UP1 confirm previous data that this portion of A1 binds single stranded nucleic acids non-co-operatively. UP1 clearly shows a preference for single-stranded nucleic acids with a 2'-OH, since its affinity for poly(U) is three times higher than for poly(dU), and five times higher than its affinity for poly(2'-OCH3U). The nucleic acid-interactive properties of the C-domain were further examined by preparing a synthetic peptide polymer (M(r) approximately 12,000) containing about seven repeats of a 16-residue sequence, GNFGGGRGGNYGGSRG, which in turn comprises two copies of the C-terminal consensus, GN(F/Y)GG(G/S)RG. The polymer of this sequence exhibited significant affinity for the fluorescent polyribonucleotide, poly(ethenoadenylic acid), binding stoichiometrically at < or = 0.2 M-Na+. Complex formation was accompanied by an increase in aggregate formation, as indicated by the appearance of scattering. For purposes of comparison, the data were analyzed via the linear co-operative model of McGhee and von Hippel, though this model may not be fully descriptive of the protein-nucleic acid complex(es) formed in this case. In contrast to the non co-operative binding mode of the UP1 domain, the C-polymer exhibited moderate co operativity, comparable to that seen with full-length A1. Although addition of sufficient NaCl reversed the interaction, a sigmoidal binding isotherm could still be observed (with sufficient added polymer) at 0.8 M-NaCl. This suggests that non-electrostatic interactions contribute significantly to the free energy of binding.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8445654 TI - The gut esterase gene (ges-1) from the nematodes Caenorhabditis elegans and Caenorhabditis briggsae. AB - The ges-1 gene codes for a non-specific carboxylesterase that is normally expressed only in the intestine of the nematode Caenorhabditis elegans. In the current paper, we describe the cloning and characterization of the ges-1 gene from C. elegans, as well as the homologous gene from the nematode Caenorhabditis briggsae. The ges-1 esterases from the two nematodes are 83% identical at the amino acid level and contain regions of significant similarity to insect and mammalian esterases; these conserved regions can be identified with residues believed to be necessary for esterase function. The ges-1 mRNAs from both C. elegans and C. briggsae are trans-spliced. The coding regions, the codon bias and the splicing signals of the two ges-1 genes are quite similar and most (6/7) of the intron positions are retained precisely. Yet, the flanking sequences of the two ges-1 genes appear to have diverged almost completely. For example, the C. elegans ges-1 5'-flanking region (as well as several introns) contains copies of three different SINE-like sequences, previously identified near the hsp-16 genes, near the unc-22 gene and in a repetitive element CeRep-3; none of these elements are found in the C. briggsae ges-1 gene. We show that: (1) the C. elegans ges-1 gene can be used to transform C. briggsae, whereupon expression of the exogenous ges-1 gene is confined to the C. briggsae intestine; (2) the ges-1 homologue cloned from C. briggsae can be transformed into C. elegans, whereupon it is expressed largely in the C. elegans intestine; and (3) a 5'-deletion of the C. elegans ges-1 gene that we have previously shown to be expressed in the C. elegans pharynx is also expressed in the pharynx of C. briggsae (either in the presence or absence of vector sequences). These results suggest that the ges-1 gene control circuits have been maintained between the two nematode species, despite the divergent 5'-flanking sequences of the gene. This raises the question of the evolutionary distance between C. elegans and C. briggsae and we attempt to estimate the C. elegans-C. briggsae divergence time by analysing the rate of synonymous substitutions in coding regions of ges-1 and six other C. elegans-C. briggsae gene pairs. We propose a new method of analysis, which attempts to remove rate differences found between different genes by extrapolating to zero codon bias.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8445655 TI - Nuclear control of the messenger RNA expression for mitochondrial ATPase subunit 9 in a new yeast mutant. AB - A new temperature-sensitive nuclear mutant of Saccharomyces cerevisiae altered in the expression of the mitochondrially encoded ATPase 9 gene was identified. Analysis of several mitochondrial transcripts reveals the selective loss of the messenger RNA for the ATPase 9 subunit under restrictive temperature conditions. This defect results in a respiratory deficiency of the yeast cells. RNA synthesis studied with isolated mitochondria gives first evidence that the mitochondrial transcription process does not react in a temperature-sensitive way. Therefore, it is concluded that the loss of the transcript is due to specific posttranscriptional degradation. Further on it is demonstrated that all the observed effects in the mutant are caused by only one mutated nuclear gene. The mutant strain was transformed with a genomic yeast library and a complementary DNA fragment was obtained. Molecular characterization of the respective DNA clone identified a new gene, which we propose to call NCA1 (Nuclear Control of ATPase messenger RNA expression). Complete inactivation of this gene by insertion mutagenesis in the chromosome leads to a permanent respiratory defect of the cell. Localization of the insertion locus in the yeast genome and complementation studies with the temperature-sensitive mutant indicate that the two mutations are allelic. PMID- 8445656 TI - On the location of histones H1 and H5 in the chromatin fiber. Studies with immobilized trypsin and chymotrypsin. AB - The location of linker histones H1 and H5 in chicken erythrocyte chromatin was studied as a function of the fiber structure by the use of proteolytic enzymes immobilized onto Immobilon membranes. The immobilization of trypsin and chymotrypsin creates proteolytic probes, specific respectively to the terminal portions of the molecules or to the phenylalanine in the globular domain, that are incapable of penetrating into the interior of the condensed fiber. The chromatin fiber was studied in three different conformations: open zig-zag (in Tris buffer), closed zig-zag (upon addition of 10 mM-NaCl), or 30 nm fiber (upon addition of 0.35 mM-MgCl2). The results from digestion experiments performed on linker histones either in chicken erythrocyte chromatin, or free in solution or bound in mononucleosomes revealed several features relevant to linker histone location: (1) histone H5 is more protected than histone H1 in the fiber; (2) the N and C-terminal portions of histone H1 do not change their accessibility, and hence their location, upon compaction of the fiber; this behavior of H1 is in contrast to that of histone H5, whose tails become significantly internalized in the 30 nm fiber; (3) phenylalanine in the globular domain of both H1 and H5 is inaccessible (buried) both in the fiber and in the mononucleosomal particle. Sedimentation velocity measurements performed during the course of trypsin digestion demonstrate that the conformation of the fiber is highly sensitive to even a few cuts in some of the linker histone molecules; hence, the linker histones are an important factor in the organization of the fiber in all its different condensation states. PMID- 8445657 TI - Structure of hen lysozyme in solution. AB - The structure of the 129-residue protein hen lysozyme has been determined in solution by two-dimensional 1H nuclear magnetic resonance methods. 1158 NOE distance restraints, and 68 phi and 24 chi 1 dihedral angle restraints were employed in conjunction with distance geometry and simulated annealing procedures. The overall C alpha root-mean-square deviation from the average for 16 calculated structures is 1.8(+/- 0.2) A, but excluding 14 residues in exposed disordered regions, this value reduces to 1.3(+/- 0.2) A. Regions of secondary structure, and the four alpha-helices in particular, are well defined (C alpha root-mean-square deviation 0.8(+/- 0.3) A for helices). The main-chain fold is closely similar to structures of the protein in the crystalline state. Furthermore, many of the internal side-chains are found in well-defined conformational states in the solution structures, and these correspond well with the conformational states found in the crystal. The general high level of definition of mainchain and many internal side-chains in the solution structures is reinforced by the results of an analysis of coupling constants and ring current shifts. Many side-chains on the surface, however, are highly disordered amongst the set of solution structures. In certain cases this disorder has been shown to be dynamic in origin by the examination of 3J alpha beta coupling constants. PMID- 8445658 TI - Refined 1.8 A X-ray crystal structure of astacin, a zinc-endopeptidase from the crayfish Astacus astacus L. Structure determination, refinement, molecular structure and comparison with thermolysin. AB - Astacin, a 200 residue digestive zinc-endopeptidase from the crayfish Astacus astacus L., is the prototype of the "astacin family", which comprises several membrane-bound mammalian endopeptidases and developmentally implicated regulatory proteins. Large trigonal crystals of astacin were grown, and X-ray reflection data to 1.8 A resolution were collected. The astacin structure has been solved by multiple isomorphous replacement using six heavy-atom derivatives, and refined to a crystallographic R-value of 0.158 applying stringent constraints. All 200 residues are clearly defined by electron density; 181 solvent molecules have been localized. Besides the native structure, the structures of Hg-astacin (with a mercury ion replacing the zinc) and of the apoenzyme were also refined. The astacin molecule exhibits a kidney-like shape. It consists of an amino-terminal and a carboxy-terminal domain, with a deep active-site cleft in between. The zinc ion, located at the bottom of this cleft, is co-ordinated in a novel trigonal bipyramidal geometry by three histidine residues, a tyrosine and by a water molecule, which is also bound to the carboxylate side-chain of Glu93. The amino terminal domain of astacin consists mainly of two long alpha-helices, one centrally located and one more peripheral, and of a five-stranded pleated beta sheet. The amino terminus protrudes into an internal, water-filled cavity of the lower domain and forms a buried salt bridge with Glu103; amino-terminally extended pro-forms of astacin are thus not compatible with this structure. The carboxy-terminal domain of astacin is mainly organized in several turns and irregular structures. Because they share sequence identity of about 35%, the structures of the proteolytic domains of the other "astacin" members must be quite similar to astacin. Only a few very short deletions and insertions quite distant from the active-site distinguish their structures from astacin. The five stranded beta-sheet and the two helices of the amino-terminal domain of astacin are topologically similar to the structure observed in the archetypal zinc endopeptidase thermolysin; the rest of the structures are, in contrast, completely unrelated in astacin and thermolysin. The zinc ion, the central alpha helix and the zinc-liganding residues His92, Glu93 and His96 of astacin are nearly superimposable with the respective groups of thermolysin, namely with the zinc ion, the "active-site helix", and His142TL, Glu143TL and His146TL of the zinc-binding consensus motif His-Glu-Xaa-Xaa-His (where Xaa is any amino acid residue).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8445659 TI - Modeling side-chain conformation for homologous proteins using an energy-based rotamer search. AB - We have developed a computational method for accurately predicting the conformation of side-chain atoms when building a protein structure from a known homologous structure. A library of rotamers is used to model the side-chains, allowing an average of five to six different conformations per residue. Local sites of adjacent side-chains are defined throughout the protein, and all combinations of side-chain rotamers are evaluated within each site using a molecular mechanics force field enhanced by the inclusion of a solvation term. At each site, the lowest energy combination of side-chains is identified and added onto the fixed protein backbone. A series of test cases using the refined X-ray structure of alpha-lytic protease has shown that: (1) the force field can correctly predict up to 90% of side-chain rotamers; (2) the assumption of side chain rotamer geometry is usually a very good approximation; and (3) the complete combinatorial conformation search is able overcome local minima and identify the lowest energy rotamer set for the protein in the absence of a starting bias to the correct structure. Tests with several pairs of homologous proteins have shown that the algorithm is quite successful at predicting side-chain conformation even when the protein backbone used to generate side-chain positions deviates from the correct conformation. The root-mean-square (r.m.s.) deviation of predicted side chain atoms rises from 1.31 A (average r.m.s.d. 0.73 A) in a test case with the correct backbone to only 2.68 A (1.95 A average r.m.s.d.) in a test case with < 35% homology. The high accuracy of this method suggests that it may be a useful automated tool for modeling protein structure. PMID- 8445660 TI - Cranial osteogenesis in Monodelphis domestica (Didelphidae) and Macropus eugenii (Macropodidae). AB - The pattern of onset and general rate of cranial ossification are compared in two marsupials, Monodelphis domestica (Didelphidae) and Macropus eugenii (Macropodidae). In both species a similar suite of bones is present at birth, specifically those surrounding the oral cavity and the exoccipital, and in both postnatal events follow a similar course. The facial skeleton matures more rapidly than the neurocranium, which is characterized by an extended period of ossification. Most dermal bones begin ossification before most endochondral bones. Endochondral bones of the neurocranium are particularly extended in both the period of onset of ossification and the rate of ossification. These data confirm suggestions that morphology at birth is conservative in marsupials and we hypothesize that the pattern of cranial osteogenesis is related to two distinct demands. Bones that are accelerated in marsupials are correlated with a number of functional adaptations including head movements during migration, attachment to the teat, and suckling. However, the very slow osteogenesis of the neurocranium is probably correlated with the very extended period of neurogenesis. Marsupials appear to be derived relative to both monotreme and placental mammals in the precocious ossification of the bones surrounding the oral cavity, but share with monotremes an extended period of neurocranial osteogenesis. PMID- 8445661 TI - Early development of the chick embryo. AB - The ultrastructure of the early chick embryo was investigated, using scanning (SEM) and transmission electron microscopy (TEM). Eggs were obtained from the shell gland by injecting hens intravenously with a synthetic prostaglandin or arginine vasopressin. Embryos were examined during late cleavage (stages IV-VI, Eyal-Giladi and Kochav, '76), formation of the area pellucida (stages VII-XI), and formation of the hypoblast (stages X-XIV). SEM highlighted the reduction in cell number at the underside of the embryo during formation of the area pellucida although it became apparent that the thickness of the embryo is not reduced to a single layer of cells at stage X. In addition, blastomeres at the perimeter of embryos (stages V-VI) project filopodial extensions onto a smooth membrane that separates the sub-embryonic cavity from the yolk. During hypoblast formation, epiblast cells generate stellate projections at their basal aspect, thus providing a meshwork for the advancing secondary hypoblast cells. By stage XII the epiblast was one cell thick and reminiscent of a columnar epithelium when viewed transversely. Cells of the deep portion of the posterior marginal zone were distinguished morphologically in the stage XII embryo by their many cell surface projections and ruffled appearance. Blastomeres at the perimeter of stage V-VI embryos projected filopodial extensions onto a smooth membrane which separates the sub-embryonic cavity from the yolk. This membrane is presumed to be confluent with the cytolemma. Evidence is presented demonstrating the presence of intracellular membrane-bound droplets which are hypothesised to contain sub embryonic fluid. PMID- 8445662 TI - Lung cancer and smoking cessation: patterns of risk. PMID- 8445663 TI - Screening program raises questions on tumor marker's use, regulation. PMID- 8445664 TI - Researchers make slow progress in establishing prognostic indicators for the clinic. PMID- 8445666 TI - Basic breast cancer research is focus of new British research center. PMID- 8445665 TI - Committee debates use of Army breast cancer funds. PMID- 8445667 TI - Drug pricing gets further airing in Senate hearing. PMID- 8445668 TI - International workshop assesses evidence for breast screening. PMID- 8445669 TI - Older women underutilize breast cancer screening. PMID- 8445670 TI - Survey shows: American women favor mammography. PMID- 8445671 TI - A call to WAR. PMID- 8445672 TI - Photodynamic therapy in oncology: mechanisms and clinical use. AB - In photodynamic therapy (PDT), a sensitizer, light, and oxygen are used to cause photochemically induced cell death. The mechanism of cytotoxicity involves generation of singlet oxygen and other free radicals when the light-excited sensitizer loses or accepts an electron. Although selective retention of sensitizer by malignant tissue is seen in vivo, the mechanisms for this sensitizer targeting remain unclear. The first-generation sensitizers are porphyrin based and vary in lipophilicity and hydrophilicity. Targeting of the vasculature seems to be a prominent feature of the cytotoxic effect of these sensitizers in vivo, with resulting necrosis. Treatment depth varies with the wavelength of light that activates the sensitizer used, and the second-generation sensitizers are activated at longer wavelengths, allowing for a 30% increase in treatment depths. The selectivity of targeting can be increased when the sensitizer is delivered with the use of liposomes or monoclonal antibodies specific for tumor antigens. Studies have demonstrated direct effects of PDT on immune effector cells, specifically those with lineage from macrophages or other monocytes. Clinically, this therapy has been chiefly used for palliation of endobronchial and esophageal obstruction, as well as for treatment of bladder carcinomas, skin malignancies, and brain tumors. The future of PDT rests in defining its use either as an intraoperative adjuvant to marginal surgical procedures or as a primary treatment for superficial malignancies. Phase III trials in esophageal cancer and lung cancer are in progress and will help in evaluation of whether Photofrin II, the most widely used sensitizer, can be added to the oncologic armamentarium, pending approval from the U.S. Food and Drug Administration. PMID- 8445673 TI - Patterns of absolute risk of lung cancer mortality in former smokers. AB - BACKGROUND: It is well known that the relative risk (RR) of lung cancer mortality decreases following smoking cessation compared with the risk in persons who continue to smoke. However, changes in the absolute risk of lung cancer death following smoking cessation are not well documented. Further, few studies have examined the effect of age at smoking cessation on subsequent lung cancer death risk. PURPOSE: The purpose of this study was to examine and compare absolute and relative lung cancer death risks in former smokers as a function of age at cessation. METHODS: Using the American Cancer Society's Cancer Prevention Study II, a prospective cohort study with 6 years of follow-up, we modeled absolute risk of lung cancer mortality in individuals who had never smoked and in current and former smokers. The model was fit with the use of person-years logistic regression analysis. RESULTS: Similar patterns of absolute risk of lung cancer death by age were found for all ages of smoking cessation up to the mid-60s. Lower lung cancer death risk was observed for those quitting earlier in life, and the risk for all former smokers was significantly lower than that for current smokers. For those quitting between ages 30 and 49, lung cancer death risk rose gradually with age at a rate slightly greater than that for those who had never smoked. Lung cancer death risk for former smokers quitting between ages 50 and 64 leveled off near the risk attained at the time of quitting until around age 75, when it rose sharply. At age 75, the RR for former smokers compared with current smokers was approximately 45% for those quitting in their early 60s, approximately 20% for those quitting in their early 50s, and less than 10% for those quitting in their 30s. For those who had never smoked, the RR at age 75 is less than 5%. CONCLUSIONS: In terms of reduced risk of lung cancer mortality, smoking cessation is beneficial at any age, with much greater benefits accruing to those quitting at younger ages. Unlike previous research, which has primarily examined the effects of cessation as a function of years since quitting, our results demonstrate that age at cessation has a major impact on subsequent lung cancer risks. IMPLICATIONS: Smokers of all ages should be encouraged to quit because cessation at any age decreases lung cancer risk relative to that of current smokers. PMID- 8445674 TI - Racial differences in risk of oral and pharyngeal cancer: alcohol, tobacco, and other determinants. AB - BACKGROUND: In the United States, Blacks have increasingly higher rates of oral and pharyngeal cancer (oral cancer) than Whites, but determinants of the racial disparity have not been clear. PURPOSE: The purpose of this study was to explore reasons for the higher incidence of oral cancer among Blacks than Whites. METHODS: We used data from a large, population-based case-control study of oral cancer risk factors conducted in four areas of the United States. On the basis of interviews that ascertained characteristics of 1065 oral cancer patients (871 Whites and 194 Blacks) and 1182 controls (979 Whites and 203 Blacks), we examined racial differences in exposure prevalences and relative risks for a number of known etiologic factors, including tobacco and alcohol consumption, diet, and socioeconomic and other variables. To evaluate the extent to which the major risk factors explained the excess risk of oral cancer among Blacks, population attributable risks were calculated. RESULTS: Differences with respect to alcohol consumption, especially among current smokers, emerged as the most important explanatory variables. After adjusting for smoking, heavy drinking (> or = 30 drinks/week) resulted in a 17-fold increased risk among Blacks and a ninefold increase among Whites. Among drinkers, Blacks tended to drink more than Whites. Also, a higher (P = .01) percentage of Blacks (37%) than Whites (28%) were current smokers, although there were little or no racial differences in relative risks or patterns of use for other smoking variables, including number of cigarettes smoked per day, years of smoking, and age started smoking. From population-attributable risk calculations, we estimated that differences in alcohol and tobacco use account for the bulk of the higher incidence of oral cancer among Blacks in the United States and that, in the absence of alcohol and tobacco, the rates of this cancer according to race (Black, White) and gender would be nearly equal. With regard to other potential etiologic factors, protective effects provided by higher dietary intake of fruits and vitamin C were more pronounced for Whites, while Blacks more often tended to be in sociodemographic and medical or dental health categories associated with increased risk. CONCLUSIONS: These analyses provide evidence that various environmental or lifestyle determinants of oral cancer may contribute to the higher oral cancer rates in Blacks than in Whites in the United States, but that patterns and risks associated with alcohol consumption, particularly among current smokers, are the most important contributors to the excess risk in Blacks. IMPLICATIONS: These findings suggest that the key to prevention of oral and pharyngeal cancers among both Blacks and Whites is reduced intake of alcoholic beverages and, because of strong interactive effects, the cessation of smoking. PMID- 8445675 TI - Relationship between environmental tobacco smoke exposure and carcinogen hemoglobin adduct levels in nonsmokers. AB - BACKGROUND: A potent bladder carcinogen for workers in the dye industry, 4 aminobiphenyl (4-ABP), is present in environmental tobacco smoke and has been shown to bond covalently with hemoglobin. PURPOSE: The goal of this study was to examine the relationship between exposure to environmental tobacco smoke and levels of 4-ABP-hemoglobin adducts in nonsmoking pregnant women and to compare adduct levels in those women with levels in smoking pregnant women. METHODS: A questionnaire on smoking and exposure to environmental tobacco smoke was administered to 15 pregnant women who smoked cigarettes and 40 who did not smoke. Exposure was quantified for 1 week with a personal diary and by air sampling with a monitor worn by each woman. The monitor collected nicotine by passive diffusion to a filter treated with sodium bisulfate, and the deposit on the filter was analyzed by gas chromatography. Aliquots of maternal blood and cord blood collected during delivery were analyzed for 4-ABP-hemoglobin adducts by gas chromatography with negative ion chemical ionization mass spectrometry. RESULTS: The mean adduct level in smokers (184 pg of 4-ABP per gram of hemoglobin) was substantially higher than that in nonsmokers (22 pg/g). This difference was statistically significant. Among nonsmokers, the levels of 4-ABP adducts increased significantly with increasing environmental tobacco smoke level (P = .009). Those in the lowest exposure category (< 0.5 micrograms/m3 weekly average nicotine) had median 4-ABP-hemoglobin adduct levels of 15 pg of 4-ABP per gram of hemoglobin, while those in the highest exposure category (> or = 2.0 micrograms/m3) had median levels of 26 pg/g. Nonsmokers in this study had a median adduct level of 20 pg/g, and smokers had a median level of 143 pg/g. CONCLUSIONS: 4-ABP-hemoglobin adduct levels in nonsmokers were 14% of the levels in smokers, which is consistent with findings of 20% in two other studies. Nonsmokers may receive a nontrivial dose of carcinogens from environmental tobacco smoke proportional to their exposure to environmental tobacco smoke. IMPLICATION: The relationship between environmental tobacco smoke exposure and 4 ABP-hemoglobin adduct levels supports epidemiologic evidence that environmental tobacco smoke is carcinogenic to passive smokers. PMID- 8445676 TI - Growth inhibition of human lymphoma cell lines by the marine products, dolastatins 10 and 15. AB - BACKGROUND: Dolastatins 10 and 15 are small peptides isolated from the marine sea hare Dolabella auricularia. In vitro studies of these peptides have demonstrated antimitotic and antiproliferative activity and growth inhibition in hematopoietic progenitor cells. PURPOSE: The purpose of our in vitro study was to determine the biological effects of these marine peptides on growth of human lymphoma cell lines and to investigate mechanisms by which the dolastatins may act. METHODS: Cell lines DB, HT, RL, and SR were grown from the ascites or pleural effusion of four patients with lymphoma. The DB, HT, and RL cell lines are of B-cell origin, and the SR cell line appears to be a less differentiated lymphoid cell type. Cells from these lines were cultured in the presence of vincristine or dolastatin 10 or 15. [3H]Thymidine-uptake assays were used to measure effects on DNA synthesis. Cell cycle analysis using propidium iodide was performed to measure drug-induced cell-cycle arrest. DNA fragmentation was used as an assay for drug induced apoptosis and was measured by agarose gel electrophoresis. RESULTS: In the three B cell lines, dolastatin 10 was more effective than dolastatin 15. Values for concentrations required for inhibition of proliferation by 50% (IC50) were .00013-.0013 nM for dolastatin 10 in each cell line; values for dolastatin 15 were approximately .13 nM in DB and HT cells and .0013-.013 nM in RL cells. SR cells were more sensitive to dolastatin 15 than to dolastatin 10 (IC50 = .00013 .0013 nM versus .0013-.013 nM). Both dolastatins arrested more than 70% of cells in mitosis in all cell lines. This effect was reversed if the drug was removed by 4 hours, but by 8 hours of exposure, reversal was not possible. Both dolastatins 10 and 15 produced apoptosis in DB and HT cells but not in the other two cell lines. CONCLUSIONS: We have demonstrated that dolastatins 10 and 15 have a profound antiproliferative effect on four different human lymphoma cell lines and that the dolastatins are approximately 3-4 logarithms more effective as antiproliferative compounds, on a molar basis, than vincristine--a clinically useful, antiproliferative agent. These data support the hypothesis that apoptosis, as measured by DNA fragmentation, appears to be a cell-specific response and may not be directly related to the antimitotic effect of the dolostatins. IMPLICATIONS: Our results suggest that these compounds may be good candidates for development as antineoplastic agents. PMID- 8445677 TI - Decision analysis of hematopoietic growth factor use in patients receiving cancer chemotherapy. AB - BACKGROUND: Hematopoietic growth factors (HGFs) have been shown to reduce the incidence of neutropenia and fever in patients receiving cancer chemotherapy. PURPOSE: This cost analysis was designed to determine the conditions in which use of HGFs in patients receiving cancer chemotherapy is cost-effective. METHODS: We used a standard model based on decision theory; the model assumes that all patients experiencing neutropenia and fever will be hospitalized and treated with intravenous antibiotics. Data from a prospective, randomized clinical trial of granulocyte colony-stimulating factor in small-cell lung cancer treated with combination chemotherapy were used to determine baseline probabilities for control hospitalization risk and survival; proportional hospitalization risk with prophylactic HGF; and median durations of hospitalization and prophylactic HGF use. The model was analyzed by one-way and multivariate sensitivity analyses, with estimation of threshold values at which the expected cost is the same for either of two treatment options. One or more of the specific costs and durations and the probability for each group of threshold curves were varied in a sensitivity analysis that generated variable thresholds. Use of Monte Carlo analysis based on the available distributions of the main variables provided 90% confidence limits and an inference method for comparing decision options. RESULTS: The expected excess cost per treatment cycle, based on hospitalization for neutropenic fever and/or HGF administration, was $5500 for no HGF, $4750 for prophylactic HGF, and $6875 for therapeutic HGF. Sensitivity analysis provided the following thresholds for no HGF versus prophylactic HGF: control risk of hospitalization, 0.40; risk of hospitalization with HGF as a proportion of control, 0.64; total daily cost of hospitalization, $727; total daily cost of HGF, $344; duration of hospitalization, 7.3 days; and duration of HGF use, 11.0 days. Multivariate analysis revealed that conditions favoring the use of HGF on a cost basis become greater (a) as risk of hospitalization, total daily hospital cost, and duration of hospitalization increase and (b) as the proportional risk of hospitalization with HGF, daily cost of HGF, and duration of HGF treatment decrease. CONCLUSIONS: The major determinants of total excess cost were the control risk of hospitalization, the proportional reduction in risk with HGF, and the average daily hospital cost. IMPLICATIONS: Use of HGFs should be based on the risk of hospitalization for neutropenic fever and consideration of the patient population and institutional costs. PMID- 8445679 TI - Re: Case-control studies of colorectal cancer mortality: is the case made for screening sigmoidoscopy? PMID- 8445678 TI - 13-cis-retinoic acid plus interferon-alpha 2a in locally advanced squamous cell carcinoma of the cervix. PMID- 8445680 TI - Primary lymphoma of the kidney: complete remission after systemic chemotherapy. PMID- 8445681 TI - Causes of racial differences in testosterone levels of men. PMID- 8445682 TI - Pattern of infections in children under-six years old presenting with convulsions associated with fever of acute onset in a children's emergency room in Benin City, Nigeria. AB - Five-hundred-and-twenty-two infants and children aged 1 month to 6 years presenting at the Children's Emergency Room of the University of Benin Teaching Hospital with convulsions associated with fever (CAF) of acute onset were prospectively evaluated to determine the pattern of infections. Twenty-six per cent had localized infections of which 38 per cent were intracranial (meningitis = 16 per cent, cerebral malaria = 19 per cent, and encephalitis = 3 per cent) and 62 per cent were extracranial with respiratory tract infections contributing 51 per cent. Although, the prevalence of meningitis was significantly higher in 1-6 months old infants when compared with older children (47 per cent v. 12 per cent; P < 0.005), it was, none-the-less, present in all the other age groups (with a prevalence of 8-17 per cent). Seventy-four per cent of the children had no localizing signs of infection. Of these 68 per cent had malaria, 4 per cent bacteraemia, and 7 per cent malaria with bacteraemia, while no infections were identified in 21 per cent. Among children with bacteraemia Staphylococcus aureus was the commonest single isolate (33 per cent) although, overall, enterobacteriaceae were the commonest. We conclude, first, that meningitis should be excluded in all children aged under 6 years who present with CAF of acute onset and, secondly, that although anticipatory treatment for malaria is justified in children with CAF of acute onset without localizing signs of infection, consideration should also be given to the problem of bacteraemia. PMID- 8445683 TI - The Baby Friendly Hospital Initiative. PMID- 8445684 TI - Cortisol levels in children with haemoglobinopathies in north Jordan. AB - Serum cortisol levels of 100 children 3-10 years old with various haemoglobinopathies were measured. The mean cortisol levels of sickle cell trait, sickle cell disease, beta-thalassemia minor and alpha 2-thalassemia were significantly (P < 0.05) lower than those of normal subjects. The decrease in cortisol levels varied from 25 (in the sickle cell trait group) to 57 per cent (in the alpha 2-thalassemia group) of the mean cortisol levels of the control group. These results suggest the presence of hypoadrenalism and its possible association with the indicated haemoglobinopathies. PMID- 8445685 TI - Epidemiology of Pseudomonas aeruginosa infections in a neonatal intensive care unit. AB - During the 19-month study period, 48 (2 per cent) of the 2177 neonates admitted to the neonatal intensive care unit (NICU) yielded Pseudomonas aeruginosa growths in blood cultures. All these neonates had clinical and haematological evidences of sepsis. Prominent clinical features included sclerema, violaceus necrotic patches, necrotizing enterocolitis (NEC), conjugated hyperbilirubinaemia, and DIC. Over all mortality was 23 per cent, distinctly higher in premature neonates with RDS. The mean gestational age and birth weights (+/- SD) of these neonates were 36.42 (+/- 2.73) weeks and 2173.34 (+/- 567.33) g, respectively. Approximately half of the total cases had low birth weight. Other adverse perinatal events before the development of sepsis included birth asphyxia (60 per cent), neonatal resuscitation (67 per cent), meconium aspiration syndrome (29 per cent), hyaline membrane disease (8 per cent), prolonged hospitalization (44 per cent), closed incubator care (17 per cent), prolonged intravenous fluids (42 per cent), repeated blood sampling (63 per cent), and umbilical catheterization (4 per cent). Analysis of the trend of Pseudomonas sepsis in our NICU revealed six definite outbreaks (more than two cases) interspersed with occasional (one or two) cases. Six study months, however, remained free of Pseudomonas sepsis. Index case was demonstrable on seven occasions. Bacteriological surveillance of the NICU after onset of initial case/cases revealed statistically significant colonization of resuscitation equipment, baby placement sites, and various cleansing solutions by the same bacterial species (P < 0.05). It is possible that Pseudomonas was introduced to our NICU from transfer admissions from other hospitals since on four occasions index case was the one transferred from outside.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8445686 TI - Clinical spectrum and follow-up study of congenital hypothyroidism at District Hospital in India. AB - Twenty cases of clinically diagnosed congenital hypothyroidism during a 7-year period at a District Hospital in South India are analysed. A maximum of nine cases were diagnosed in the age group 1-5 years, only two before 3 months of age and five after 10 years of age. Two siblings of one family had the disease. Three children were associated with muscular hypertrophy, i.e. Kocher-Debre-Semelaigne Syndrome. Constipation and delayed milestones were the commonest symptoms (60 per cent). Classical facies (100 per cent), wide open anterior fontanella (65 per cent), coarse skin (60 per cent), and stunted growth (60 per cent) were the common physical findings. IQ was in between 30 and 40 in 60 per cent of cases. Only 50 per cent of them were followed up for a period of 1-5 years. Though physical growth was good on thyroxine IQ of above 80 was achieved in only three (30 per cent). PMID- 8445687 TI - A survey of technology and temperature control on a neonatal unit in Kathmandu, Nepal. AB - An assessment of the incubators in use at the Kathmandu Maternity Hospital neonatal unit was undertaken; this was followed by a prospective survey of neonatal temperatures on the unit. In the incubator assessment 11 studies were carried out in five incubators. Three of the thermostats in the five incubators did not work at all and those in the other two incubators were more than 3 degrees C inaccurate. All the incubator thermometers gave recordings less than the actual temperature (with a range of error: 1.3-4.4 degrees C). Six out of the 11 babies studied were hypothermic (defined as rectal temperature < 36 degrees C). In the prospective survey of temperatures a high incidence of hypothermia was found on the neonatal unit at the time of first temperature measurement (64 per cent had a rectal temperature of < 36 degrees C). A significant association between admission hypothermia and mortality was noted. Sixteen per cent (10/64) of babies admitted with temperatures < 36 degrees C died within the first week, compared to 0 (0/36) of those admitted with temperatures > or = 36 degrees C. PMID- 8445688 TI - Perinatal mortality in rural India with special reference to high risk pregnancies. AB - One-thousand-and-sixty-five pregnant mothers among a rural population of 30,000 in Uttar Pradesh were followed for 1 year. A still birth rate of 26.1 and perinatal mortality rate of 121.1 per thousand births were registered. Early neonatal mortality rate was found to be 97.4 per thousand live births. Twenty per cent of the women were identified with high risk factors. Inadequate or no antenatal care, bad obstetric history, and prolonged labour attributed to 13, 20, and 27 per cent of the risk, respectively, with a respective relative risk of 2.23, 3.1, and 4.09 times. These three factors were found to be the major and significant contributors to high perinatal mortality amongst the 'high risk' group. Selective extension of comprehensive M.C.H. Care to this group using the high risk approach is expected to lower perinatal mortality in rural community where M.C.H. services are far from optimum. PMID- 8445689 TI - Relactation in mothers of children over 12 months. AB - Six Australian children aged 12-48 months whose mothers relactated through suckling alone are described. During the period between the initial weaning and relactation the mothers had not attempted to maintain lactation; nor had the children been breastfed by any other person, yet they were able to 'milk' the breast. All mothers produced fluid from their breasts in response to suckling. In all but one case (Case 2) the initiative came from the child and there was no performance anxiety as the mothers' aims were other than milk production, for instance, to soothe the child after separation. All except one child continued to breastfeed for many months after relactation. PMID- 8445690 TI - Chest circumference as an indicator of low birth weight in Zimbabwe. PMID- 8445691 TI - 8-year clinical experience in cerebral palsy. AB - The changes in frequency and distribution of the clinical types of cerebral palsy (CP) were evaluated in 1873 CP cases admitted to the Department of Pediatric Neurology between 1982 and 1989. The observed panorama of CP was unlike the situation in developed countries. The majority of the cases were term-born and perinatal risk factors were noted to play the predominant role in the etiology of these cases. On the other hand, the most common type of CP was spastic quadriplegia where as spastic diplegia cases were less commonly encountered. These differences led us to conclude that the clinical panorama of CP might be an indicator of socio-economic development. PMID- 8445692 TI - A controlled trial of weighing with the Direct Recording Scales by the mothers in a village based growth monitoring programme in Ghana. AB - The Direct Recording Scales from Teaching aids at low cost (TALC) have been designed to overcome some of the deficiencies in present growth monitoring programmes. This is the full account of the first controlled trial of their use by 38 mothers for 6 months in a rural West African village. The mothers found weighing with the Direct Recording Scales easier to perform and more accurate than the control group using the dial scales. Their understanding of growth monitoring significantly improved as assessed by a questionnaire. Additionally, the mothers were proud to actively participate in the village--based weighing, which allowed more time for full discussions of their child's growth while leaving time free for the visiting health worker to spend on other aspects of Primary Health Care. PMID- 8445693 TI - Breastfeeding patterns and promotion of infant formula in the Republic of Yemen. PMID- 8445694 TI - Endoscopically-controlled electrohydraulic intracorporeal shock wave lithotripsy (EISL) of salivary stones. AB - Twenty-nine patients with salivary stones were treated with the endoscopically controlled electrohydraulic shock wave lithotripsy (EISL). This new minimally invasive treatment of sialolithiasis is performed under local anesthesia on an outpatient basis with little inconvenience to the patient. For endoscopy, a flexible fibroscope with an additional probe to generate shock waves is placed into the submandibular duct and advanced until the stone is identified. For shock wave-induced stone disintegration, the probe electrode must be placed 1 mm in front of the concrement. The shock waves are generated by a sparkover at the tip of the probe. By means of the endoscopically-controlled shock wave lithotripsy it was possible to achieve complete stone fragmentation in 20 out of 29 patients without serious side effects. In three patients, only partial stone fragmentation could be achieved due to the stone quality. Endoscopically-controlled electrohydraulic intracorporeal shock wave lithotripsy represents a novel minimally invasive therapy for endoscopically accessible salivary gland stones. The advantage in comparison to the endoscopically-controlled laser lithotripsy will be discussed. PMID- 8445695 TI - Adult-type rhabdomyoma of the submandibular region. AB - Adult-type rhabdomyoma is a rare benign tumor which occurs mainly in the head and neck region of middle-aged patients. We present a case of rhabdomyoma of the submandibular region. Clinical and histologic features are discussed as well as differential diagnosis and proper treatment. Finally, all previous reports of adult rhabdomyoma cases are reviewed. PMID- 8445696 TI - Glossopharyngeal neuralgia and syncope secondary to neck malignancy. AB - Glossopharyngeal neuralgia with syncope, secondary to a malignant tumor in the neck, is an extremely rare condition. Dysman, et al more recently described a case in 1980. In this case, it was initially difficult to confirm the proper diagnosis since recurrent tumor was not able to be detected either clinically or radiographically. The patient was initially treated as syncope due to hypotension and bradycardia, but pacemaker therapy failed to control the cardiovascular abnormality. The administration of Dilantin, however, seems to improve the neuralgic pain and syncope. Due to a poor prognosis from the neck tumor recurrence, and patient refusal of further therapy, no surgical control of symptoms was attempted in this patient. This report is presented to make otolaryngologists aware of this condition. PMID- 8445697 TI - Open rhinoplasty: its past and future. AB - Open rhinoplasty is a surgical approach to the nose. This article will review the history of the open rhinoplasty technique, comment on its advantages and disadvantages, illustrate the surgical technique and review modifications and developments that have arisen. Although of primary concern to nasal surgeons, the open approach will be of interest to all surgeons, regardless of their area of focus. PMID- 8445699 TI - Epiglottoplasty in the treatment of laryngomalacia. AB - Laryngomalacia is the most common congenital laryngeal anomaly. Usually the symptoms are mild, do not interfere with growth and development and resolve spontaneously. Occasionally it results in failure to thrive, apnea and cardiopulmonary disease. These children have traditionally experienced a stormy course, sometimes ending with tracheostomy. We present our experience with a recently described endoscopic procedure that involves the excision of redundant mucosa over the lateral edges of the epiglottis, aryepiglottic folds, arytenoids and corniculate cartilages. In six cases operated at the Montreal Children's Hospital there were no complications. Their pre-operative symptoms resolved after surgery. The cases, indications and complications reported in the literature are discussed. We conclude that in certain severe cases of laryngomalacia, epiglottoplasty is a useful and safe tool. PMID- 8445698 TI - Branchiogenic carcinoma. AB - The validity of the diagnosis 'branchiogenic carcinoma' has been debated for many years. Recently, Micheau, et al recorded 21 cases of metastatic squamous carcinoma that presented with cystic masses in the neck and concluded that most, if not all of the reported cases of branchiogenic carcinoma, were in fact of similar origin. This report contains histological evidence of the origin of squamous cell carcinoma from a branchiogenic cyst in an otherwise healthy young man. Five similarly convincing reports from the literature are also reviewed. PMID- 8445700 TI - Ear examination: the otoscope. PMID- 8445701 TI - Laryngeal tuberculosis: presentation of 16 cases and review of the literature. AB - Tuberculosis of the larynx was quite common in the past and usually associated with advanced pulmonary cavitations with an overall mortality of approximately 70% before the advent of chemotherapy. Its incidence was on the decline in the last two decades; however, it seems to be on the increase in the last few years. During the past 30 years, 16 patients with laryngeal tuberculosis were investigated at the American University of Beirut, Medical Centre. Around 20% of our patients had isolated laryngeal tuberculosis with no apparent pulmonary involvement. Four patients (25%) presented with stridor and had a tracheotomy performed for the relief of their upper airway obstruction. In contrast to earlier studies, our series showed great variations as far as location and appearance of the laryngeal lesions. PMID- 8445702 TI - The effects of long-term cochlear hearing loss on the functional organization of central auditory pathways. AB - We have developed an animal model of neonatal high-frequency cochlear hearing loss to investigate the long-term effects on the central auditory pathways. Specifically, we have induced basal cochlear lesions in newborn kittens using the ototoxic aminoglycoside, amikacin. We have monitored the consequent auditory threshold elevations using auditory brainstem evoked responses (ABR) to tone pip stimuli. In the mature animal we have mapped tonotopic (cochleotopic) representation in primary auditory cortex (AI) using standard micro-electrode recording techniques, and we show that this map becomes massively re-organized. In particular, one frequency area that corresponds to the high frequency cut-off slope of the subject's audiogram appears to become greatly expanded, in some cases to take up 75% of AI surface. In general, the development of normal cochleotopic or tonotopic representation in cortex appears to depend upon the integrity of ascending sensory input from the cochlea particularly during early stages of development. With the clinician in mind, we discuss our findings in relation to practical issues. PMID- 8445703 TI - Laser surgery in otorhinolaryngology: a 10-year experience. AB - Carbon dioxide laser was introduced in ENT in the early 1970s, and is now a routine treatment modality in many departments. The CO2 laser is a non coagulating laser and works by evaporation of the tissue. Strict safety routines are important in laser treatment. However, our experiences with laser surgery are good. In the present study of 216 patients with a total of 479 treatments, we experienced no major complications. Laser surgery should be considered a valuable surgical complement, it is, however, important to gain knowledge about its pros and cons. PMID- 8445704 TI - An unusual nosocomial infection: nasotracheal myiasis. AB - A number of fly maggots were found emerging from the nose and tracheostomy site of an 82-year-old woman who had been in a coma for two months in an acute care hospital in a large Canadian city. This case history indicates that the infestation was hospital-acquired and although undoubtedly an extremely rare occurrence, at least in Canada, points out the risk of myiasis in the unconscious, debilitated patient. PMID- 8445705 TI - Tympanic membrane perforation following ventilation tube removal in a pediatric setting: a historical study. AB - This study is concerned with the rate of tympanic membrane perforation following the surgical removal of ventilation tubes. Consideration for inclusion in the study was given to all patients who had ventilation tubes surgically removed between 1982 and 1991 at The Hospital for Sick Children. All patients included in the study were followed for a minimum period of six months. The patients ranged in age from two to 13 years old, with a mean age of 4.7 years. Our study followed 203 ears which met the entry criteria. It was found that there were 21 (10.3%) documented perforations within this study group. PMID- 8445706 TI - Metastasizing neuroendocrine tumor of unknown origin found in cervical lymph nodes: a case report. AB - Neuroendocrine tumors are a diverse category of tumors that have been known to produce biologically active amines and ectopic hormones of various types. Numerous metastasizing primary lesions have been identified, however, the head and neck region is not a common site for them. Even less common than these are head and neck metastatic sites without an identifiable primary lesion. We report a case of a metastatic neuroendocrine tumor, where the primary site eluded detection despite an extensive battery of investigations. PMID- 8445707 TI - 3' junctions of oncogene-virus sequences and the mechanisms for formation of highly oncogenic retroviruses. PMID- 8445708 TI - The human immunodeficiency virus type 1 long terminal repeat specifies two different transcription complexes, only one of which is regulated by Tat. AB - The human immunodeficiency virus type 1 long terminal repeat sets up two different transcription complexes, which have been called processive and nonprocessive complexes. By mutating and substituting cis-acting sequences, we mapped elements of the human immunodeficiency virus long terminal repeat that are responsible for creating each transcription complex. Whereas processive complexes are efficiently assembled by upstream promoter elements in the absence of the TATA box, nonprocessive complexes absolutely require the TATA box. Moreover, the TATA box alone can set up these nonprocessive complexes, and nonprocessive but not processive complexes are trans activated by Tat. Finally, a strong DNA binding site between the TATA box and trans-activation-responsive region interferes with either the assembly or movement of these nonprocessive complexes and diminishes the effects of Tat. Thus, Tat affects a critical step in the formation of elongation-competent transcription complexes. PMID- 8445709 TI - A single amino acid in the PB2 gene of influenza A virus is a determinant of host range. AB - The single gene reassortant virus that derives its PB2 gene from the avian influenza A/Mallard/NY/78 virus and remaining genes from the human influenza A/Los Angeles/2/87 virus exhibits a host range restriction (hr) phenotype characterized by efficient replication in avian tissue and failure to produce plaques in mammalian Madin-Darby canine kidney cells. The hr phenotype is associated with restriction of viral replication in the respiratory tract of squirrel monkeys and humans. To identify the genetic basis of the hr phenotype, we isolated four phenotypic hr mutant viruses that acquired the ability to replicate efficiently in mammalian tissue. Segregational analysis indicated that the loss of the hr phenotype was due to a mutation in the PB2 gene itself. The nucleotide sequences of the PB2 gene of each of the four hr mutants revealed that a single amino acid substitution at position 627 (Glu-->Lys) was responsible for the restoration of the ability of the PB2 single gene reassortant to replicate in Madin-Darby canine kidney cells. Interestingly, the amino acid at position 627 in every avian influenza A virus PB2 protein analyzed to date is glutamic acid, and in every human influenza A virus PB2 protein, it is lysine. Thus, the amino acid at residue 627 of PB2 is an important determinant of host range of influenza A viruses. PMID- 8445710 TI - A binding site for transcription factor E2F is a target for trans activation of murine thymidine kinase by polyomavirus large T antigen and plays an important role in growth regulation of the gene. AB - The promoter of the murine thymidine kinase gene contains a binding site for transcription factor E2F. Using cell lines (3T3-LT) conditionally expressing polyomavirus large T antigen from a hormone-responsive promoter and reporter gene constructs carrying the thymidine kinase promoter with intact or mutated E2F sites, we show that this E2F site is the target for trans activation by the viral protein. Transcription of the growth-regulated endogenous thymidine kinase gene can be activated in serum-starved, quiescent 3T3-LT cells by induction of T antigen. Activation of transcription from the thymidine kinase promoter requires an intact binding site for the retinoblastoma protein in the T antigen. The same promoter region was furthermore shown to play a major role in growth regulation of the gene. As several other DNA synthesis enzymes also carry E2F binding sites in their promoters, our observations suggest a common mechanism of growth regulation of these genes and that they all might be targets for trans activation by DNA tumor virus proteins. PMID- 8445711 TI - High-frequency recombination mediated by polyomavirus large T antigen defective in replication. AB - We investigated the mechanism by which the large T antigen (T-Ag) of both polyomavirus and simian virus 40 (SV40) promotes homologous recombination in mammalian cells. To this end, we constructed a rat cell line, designated Hy5, that carries two mutated copies of the polyomavirus middle-T-Ag (pmt) oncogene lying as direct repeats on the same chromosome. The structure of the viral insert was devised so that intrachromosomal recombination between the pmt repeats reconstitutes wild-type pmt and yields cell populations amenable to selection for the transformed phenotype. Correction of pmt by gene conversion occurred spontaneously at a rate of ca. 1.7 x 10(-7) per cell generation and was masked by another recombination event that also led to the transformation of the Hy5 cell line. This event was identified as chromosomal inversion and overexpression of the upstream pmt copy as a result of homologous recombination between adjacent pBR322 sequences. Both events were promoted by the polyomavirus large T-Ag by several orders of magnitude, as well as by mutants defective in the initiation of viral DNA synthesis. Large T-Ag also promoted reconstitution of wild-type pmt by unequal exchange between sister chromatids, yielding structures compatible with some of the chromosomal aberrations commonly observed in transformed cells. Our data indicate that large T-Ag has a recombination-promoting activity that can be dissociated from its replicative function. PMID- 8445712 TI - An anti-lymphocytic choriomeningitis virus ribozyme expressed in tissue culture cells diminishes viral RNA levels and leads to a reduction in infectious virus yield. AB - Ribozymes, RNA molecules which cleave RNA in a sequence-specific manner, are a promising tool in the development of specific antiviral therapies. The viruses most susceptible to ribozymes may be those in which all aspects of the viral life cycle depend on RNA, with no DNA intermediate. Consequently, we have chosen as a model one such virus, the arenavirus lymphocytic choriomeningitis virus (LCMV), and have previously reported the design of specific anti-LCMV ribozymes (Z. Xing and J. L. Whitton, J. Virol. 66:1361-1369, 1992). Here we describe the establishment of several cell lines, each stably expressing an antiarenaviral ribozyme of different specificity. Expression of a single ribozyme leads to a reduction in LCMV RNA levels, and stimulation of ribozyme transcription amplifies the effect. Target site selection may be an important determinant of antiviral effectiveness, since the extent of the antiviral effect, measured by assay of viral RNA, varies with the specificity of the antiviral ribozyme expressed. Furthermore, infectious virus production is reduced approximately 100-fold. This effect is LCMV specific, as yield of a related arenavirus is not similarly curtailed. We are currently investigating the mechanism underlying the ribozyme mediated antiviral effect. PMID- 8445713 TI - Functional analysis of matrix proteins expressed from cloned genes of measles virus variants that cause subacute sclerosing panencephalitis reveals a common defect in nucleocapsid binding. AB - We have developed an in vitro nucleocapsid-binding assay for studying the function of the matrix (M) protein of measles virus (MV) (A. Hirano, A. H. Wang, A. F. Gombart, and T. C. Wong, Proc. Natl. Acad. Sci. USA, 89:8745-8749, 1992). In this communication we show that the M proteins of three MV strains that cause acute infection (Nagahata, Edmonston, and YN) bind efficiently to the viral nucleocapsids whereas the M proteins of four MV strains isolated from patients with subacute sclerosing panencephalitis (SSPE) (Biken, IP-3, Niigata, and Yamagata) fail to bind to the viral nucleocapsids. MV Biken (an SSPE-related virus) produces variant M sequences which encode two antigenically distinct forms of M protein. A serine-versus-leucine difference is responsible for the antigenic variation. MV IP-3 (an SSPE-related virus) also produces variant M sequences, some of which have been postulated to encode a functional M protein responsible for the production of an infectious revertant virus. However, the variant M proteins of Biken and IP-3 strains show no nucleocapsid-binding activity. These results demonstrate that the nucleocapsid-binding function is conserved in the M proteins of MV strains that cause acute infection and that the M proteins of MV strains that cause SSPE exhibit a common defect in this function. Analysis of chimeric M proteins indicates that mutations in the amino-terminal, carboxy proximal, or carboxy-terminal region of the M protein all abrogate nucleocapsid binding, suggesting that the M protein conformation is important for interaction with the viral nucleocapsid. PMID- 8445714 TI - Transdominant inhibition of wild-type human immunodeficiency virus type 2 replication by an envelope deletion mutant. AB - The envelope glycoprotein of human immunodeficiency virus type 2 (HIV-2) is primarily responsible for virus attachment and entry into the target cell population. We constructed an HIV-2 mutant virus containing an in-frame deletion within the putative CD4-binding sequences of the envelope glycoprotein and confirmed that the mutant envelope is unable to bind CD4 and that the mutant virus is noninfectious. To investigate whether this mutant could dominantly interfere with wild-type replication, we coexpressed proviral DNAs of both wild type and mutant viruses in cells and assayed the production of infectious HIV-2 virions. Interference with virus replication was indeed observed with mutant DNA, and a maximal effect was achieved with 10-fold excess mutant DNA over wild-type DNA in the cotransfection experiments. The transdominant effect on virus replication does not appear to be at the level of wild-type envelope expression or gp120-CD4 interaction. Rather, the interference may be at the level of mixed oligomer formation during progeny virus assembly and may occur by either destabilizing the multimeric structure of gp120 or forming a defective mixed multimeric gp120 which is unable to complete the receptor binding and/or postbinding events needed for infection. PMID- 8445715 TI - Saturable attachment sites for polyhedron-derived baculovirus on insect cells and evidence for entry via direct membrane fusion. AB - This research provides the first evidence for specific receptor binding of polyhedron-derived baculovirus (PDV) to host cells and to lepidopteran brush border membrane vesicles (BBMV) and demonstration of entry via a nonendocytotic pathway involving direct membrane fusion. The technique of fluorescence-activated cell sorting analysis was used to investigate the specificity of binding between the PDV phenotype of Lymantria dispar nuclear polyhedrosis virus (LdNPV) and host membranes. Fluorescein isothiocyanate-labeled PDV was found to bind in a saturable manner to the gypsy moth cell line IPLB-LdEIta and to L. dispar BBMV. The IPLB-LdEIta cell line was found to possess approximately 10(6) PDV-specific receptor sites per cell. Excess levels of unlabeled PDV were highly efficient in competing with fluorescein isothiocyanate-labeled PDV for limited receptor sites, further supporting the specificity of the interaction. Major reductions in virus binding (as high as 70%) after protease treatment of cells indicated that a protein receptor is involved. A fluorescence dequenching assay of membrane fusion with octadecyl rhodamine B (R18)-labeled PDV was used to identify PDV fusion to host cells and BBMV. Direct membrane fusion of PDV occurred at 27 degrees C to both target membranes as well as at 4 degrees C at approximately 55% of the levels achieved at 27 degrees C. Viral fusion to BBMV occurred throughout the pH range of 4 to 11, with dramatically increased fusion levels (threefold) under the alkaline conditions normal for lepidopteran larval midguts. Treatment of cells with chloroquine, a lysosomotropic agent, did not significantly affect PDV fusion to cells or infectivity in tissue culture assays. PMID- 8445716 TI - Assembly of functional Sindbis virus RNA replication complexes: requirement for coexpression of P123 and P34. AB - A vaccinia virus transient expression system was used to determine which of the Sindbis virus (SIN) proteins and/or polyproteins are necessary for the formation of active replication complexes and, in particular, to analyze the role of nsP4, the putative polymerase, versus P34 in RNA replication. We generated vaccinia virus recombinants in which the cDNA for the entire SIN nonstructural coding region as well as cDNA copies of the individual nonstructural proteins (nsPs) and several intermediate polyproteins were placed downstream of the promoter for T7 RNA polymerase and the encephalomyocarditis virus 5' untranslated region. The proteins expressed by the vaccinia virus recombinants comigrate with authentic proteins synthesized in SIN-infected cells, and the polyproteins appear to be processed to the individual proteins of the correct size. To examine the replication efficiencies of different protein combinations, a vaccinia virus recombinant was designed to express an engineered substrate RNA which could serve as a template for replication and subgenomic mRNA transcription by the SIN nsPs. Expression of the entire SIN nonstructural coding region resulted in the synthesis of high levels of both genomic and subgenomic RNAs derived from the engineered template. No RNA replication could be detected during coexpression of the four individual nsPs, although the proteins were indistinguishable, in terms of electrophoretic mobility, from those synthesized in SIN-infected cells. Coexpression of polyproteins P12, P23, and/or P34 with the individual nsPs also did not result in detectable levels of RNA replication. However, when P123 and P34 were coexpressed, efficient RNA replication and subgenomic mRNA transcription of the substrate RNA was observed. Coexpression of nsP4 with P123 resulted in the synthesis of only minus-strand RNAs. These studies show that expression of both P123 and P34 is necessary for establishment of functional RNA replication and transcription complexes and raise the possibility that the polyproteins themselves may be functional components of these complexes. In addition, these data indicate that an nsP4 moiety expressed independently with an additional N terminal methionine is capable of functioning in minus-strand but not plus-strand RNA synthesis. PMID- 8445717 TI - Roles of nonstructural polyproteins and cleavage products in regulating Sindbis virus RNA replication and transcription. AB - Using vaccinia virus to express Sindbis virus (SIN) nonstructural proteins (nsPs) and template RNAs, we showed previously that synthesis of all three viral RNAs occurred only during expression of either the entire nonstructural coding region or the polyprotein precursors P123 and P34. In this report, the vaccinia virus system was used to express cleavage-defective polyproteins and nsP4 proteins containing various N-terminal extensions to directly examine the roles of the P123 and P34 polyproteins in RNA replication. Replication and subgenomic mRNA transcription occurred during coexpression of P34 and P123 polyproteins in which cleavage was blocked at either or both of the 1/2 and 2/3 sites. For all cleavage defective P123 polyproteins, however, the ratio of subgenomic to genomic RNA was decreased, suggesting that both the 1/2 and 2/3 cleavages are required for efficient subgenomic RNA transcription. These studies indicate that the uncleaved P123 polyprotein can function as a component of the viral replicase capable of synthesizing both plus- and minus-strand RNAs. In contrast, cleavage-defective P34 was unable to function in RNA replication, even in complementation experiments in which minus-strand RNAs were provided by nsP4. A P34 polyprotein whose cleavage site was not altered could only function in RNA replication in the presence of an active nsP2 protease. Although nsP4, the putative RNA polymerase, was capable of synthesizing only minus-strand RNAs during coexpression with P123, the addition of only 22 upstream residues to nsP4 allowed both replication and transcription of subgenomic RNA to occur. These data show that the conserved domains of both nsP3 and the nsP4 polymerase do not need to be present in a P34 polyprotein to form a functional plus-strand replicase-transcriptase and suggest that the presence of an active nsP2 protease and a cleavable 3/4 site correlates with synthesis of all virus-specific RNA species. PMID- 8445718 TI - Two factors that bind to highly conserved sequences in mammalian type C retroviral enhancers. AB - The transcriptional enhancers of the Moloney and Friend murine leukemia viruses (MLV) are important determinants of viral pathogenicity. We used electrophoretic mobility shift and methylation interference assays to study nuclear factors which bind to a region of these enhancers whose sequence is identical between Moloney and Friend viruses and particularly highly conserved among 35 mammalian type C retroviruses whose enhancer sequences have been aligned (E. Golemis, N. A. Speck, and N. Hopkins, J. Virol. 64:534-542, 1990). Previous studies identified sites for the leukemia virus factor b (LVb) and core proteins in this region (N. A. Speck and D. Baltimore, Mol. Cell. Biol. 7:1101-1110, 1987) as well as a site, overlapping those for LVb and core, for a third factor (N. R. Manley, M. A. O'Connell, P. A. Sharp, and N. Hopkins, J. Virol. 63:4210-4223, 1989). Surprisingly, the latter factor appeared to also bind two sites identified in the Friend MLV enhancer, Friend virus factor a and b1 (FVa and FVb1) sites, although the sequence basis for the ability of the protein to bind these diverse sites was not apparent. Here we describe the further characterization of this binding activity, termed MCREF-1 (for mammalian type C retrovirus enhancer factor 1), and the identification of a consensus sequence for its binding, GGN8GG. We also identify a factor, abundant in mouse T-cell lines and designated LVt, which binds to two sites in the Moloney MLV enhancer, overlapping the previously identified LVb and LVc binding sites. These sites contain the consensus binding site for the Ets family of proteins. We speculate on how distinct arrays of these factors may influence the disease-inducing phenotype. PMID- 8445719 TI - Characterization of a protein that binds multiple sequences in mammalian type C retrovirus enhancers. AB - Mammalian type C retrovirus enhancer factor 1 (MCREF-1) is a nuclear protein that binds several directly repeated sequences (CNGGN6CNGG) in the Moloney and Friend murine leukemia virus (MLV) enhancers (N. R. Manley, M. O'Connell, W. Sun, N. A. Speck, and N. Hopkins, J. Virol. 67:1967-1975, 1993). In this paper, we describe the partial purification of MCREF-1 from calf thymus nuclei and further characterize the binding properties of MCREF-1. MCREF-1 binds four sites in the Moloney MLV enhancer and three sites in the Friend MLV enhancer. Ethylation interference analysis suggests that the MCREF-1 binding site spans two adjacent minor grooves of DNA. PMID- 8445720 TI - Epstein-Barr virus nuclear proteins EBNA-3A and EBNA-3C are essential for B lymphocyte growth transformation. AB - Recombinant Epstein-Barr viruses (EBV) with a translation termination codon mutation inserted into the nuclear protein 3A (EBNA-3A) or 3C (EBNA-3C) open reading frame were generated by second-site homologous recombination. These mutant viruses were used to infect primary B lymphocytes to assess the requirement of EBNA-3A or -3C for growth transformation. The frequency of obtaining transformants infected with a wild-type EBNA-3A recombinant EBV was 10 to 15%. In contrast, the frequency of obtaining transformants infected with a mutant EBNA-3A recombinant EBV was only 1.4% (9 mutants in 627 transformants analyzed). Transformants infected with mutant EBNA-3A recombinant virus could be obtained only by coinfection with another transformation-defective EBV which provided wild-type EBNA-3A in trans. Cells infected with mutant EBNA-3A recombinant virus lost the EBNA-3A mutation with expansion of the culture. The decreased frequency of recovery of the EBNA-3A mutation, the requirement for transformation-defective EBV coinfection, and the inability to maintain the EBNA 3A mutation indicate that EBNA-3A is essential or critical for lymphocyte growth transformation and that the EBNA-3A mutation has a partial dominant negative effect. Five transformants infected with mutant EBNA-3C recombinant virus EBV were also identified and expanded. All five also required wild-type EBNA-3C in trans. Serial passage of the mutant recombinant virus into primary B lymphocytes resulted in transformants only when wild-type EBNA-3C was provided in trans by coinfection with a transformation-defective EBV carrying a wild-type EBNA-3C gene. A secondary recombinant virus in which the mutated EBNA-3C gene was replaced by wild-type EBNA-3C was able to transform B lymphocytes. Thus, EBNA-3C is also essential or critical for primary B-lymphocyte growth transformation. PMID- 8445721 TI - trans-dominant interference with virus infection at two different stages by a mutant envelope protein of Friend murine leukemia virus. AB - A dominant negative mutant Friend murine leukemia virus (FMLV) env gene was cloned from an immunoselected Friend erythroleukemia cell. The mutant env had a point mutation which resulted in a Cys-to-Arg substitution at the 361st amino acid in the FMLV envelope protein (Env). The mutant Env was retained in the endoplasmic reticulum (ER) and accumulated because of its slow degradation. The NIH 3T3 cells expressing the mutant env were resistant to ecotropic Moloney MLV (MoMLV) penetration, suggesting that the mutant Env traps the ecotropic MLV receptors in the ER. When the mutant env gene was transfected into and expressed in the cells persistently infected with MoMLV, the wild-type Env was trapped in the ER, and the MoMLV production was suppressed. Thus, the mutant Env accumulating in the ER trans-dominantly and efficiently interfered with the ecotropic MLV infection at both the early and the late stages. PMID- 8445722 TI - Envelope-binding domain in the cationic amino acid transporter determines the host range of ecotropic murine retroviruses. AB - Infection of rodent cells by ecotropic type C retroviruses requires the expression of a cationic amino acid transporter composed of multiple membrane spanning domains. By exchanging portions of cDNAs encoding the permissive mouse and nonpermissive human transporters and examining their abilities to specify virus infection upon expression in human 293 cells, we have identified the amino acid residues in the extracellular loop connecting the fifth and sixth membrane spanning segments of the mouse transporter that are required for both envelope gp70 binding and infection. These findings strongly suggest that the role of the mouse transporter in determining infection is to provide an envelope-binding site. This role is analogous to those of host membrane proteins composed of a single membrane-spanning domain that serve as binding proteins or receptors for other enveloped viruses such as human immunodeficiency virus, Epstein-Barr virus, and murine and human coronaviruses. PMID- 8445723 TI - Characterization of a bicistronic retroviral vector composed of the swine vesicular disease virus internal ribosome entry site. AB - We cloned the 5' nontranslated region (NTR) from the genome of swine vesicular disease virus (SVDV), a member of the family Picornaviridae, and used it to construct a bicistronic retroviral vector. The vector is characterized by coexpression of two genes from a single transcript. We found that inclusion of the 5' NTR of SVDV did not negate the viral vector titer. Protein analysis indicated that the 5' NTR could efficiently direct internal initiation, thus allowing the downstream gene to be translated. Translation of the internally initiated porcine growth hormone gene was about 30-fold less than that when the porcine growth hormone gene was at the upstream position in NIH 3T3 cells but was about equivalent to that in HeLa cells, implying that some cellular factors that stimulated internal initiation of the SVDV 5' NTR are present in HeLa cells. However, in G418-selected clones, the Neor-encoding gene was expressed with equivalent efficiency either at a downstream position or at an upstream position in either NIH 3T3 or HeLa cells. Compared with the conventional double-gene vector or the U3-based vector, the bicistronic vector coexpressed two genes much more efficiently, owing to elimination of promoter interference. Furthermore, this type of vector infected and expressed the target genes efficiently in two primary cell lines, rat embryo and human skin fibroblast cells, which we tested. These experimental data suggest a better design for the retroviral vector and provide evidence that internal initiation of the SVDV 5' NTR was stimulated cell specifically. PMID- 8445724 TI - Three baculovirus genes involved in late and very late gene expression: ie-1, ie n, and lef-2. AB - We developed a method to identify baculovirus genes required for late and very late gene expression that is based on subtraction of clones from an Autographa californica nuclear polyhedrosis virus genomic library which is able to trans activate promoters of reporter plasmids in transient expression assays. Using this assay, we found that three genes located between 83.7 and 7.5 map units of the Autographa californica nuclear polyhedrosis virus genome were involved in expression from the late capsid protein (vp39) and very late polyhedrin (polh) gene promoters. Two of these genes, ie-1 and ie-n, trans regulate early genes in transient expression assays. Although ie-1 was necessary and sufficient for expression from the early promoter in our assay, it was necessary but not sufficient for expression from the vp39 and polh promoters. The presence of ie-n increased expression from the early, late, and very late classes of promoters tested. However, a third gene identified in this region was specifically required for expression from the vp39 and polh promoters. This gene, a previously sequenced 630-nucleotide open reading frame, was renamed lef-2 for late expression factor 2. We also found that other genes in the region between 83.7 and 7.5 map units were not required for expression from the promoters used in this assay, although we did not eliminate the possibility that they subtly modify expression. These genes include pe-38 and me53, early genes with zinc finger-like motifs, and the upstream exon of ie-0, which specifies an alternate form of IE-1. PMID- 8445725 TI - Characterization of mutants within the gene for the adenovirus E3 14.7-kilodalton protein which prevents cytolysis by tumor necrosis factor. AB - The 14,700-Da protein (14.7K protein) encoded by the E3 region of adenovirus has previously been shown to protect mouse cells from cytolysis by tumor necrosis factor (TNF). Delineating the sequences in the 14.7K protein that are required for this activity may provide insight into the mechanism of protection from TNF by 14.7K as well as the mechanism of TNF cytolysis. In the present study, we examined the ability of 14.7K mutants to protect cells from lysis by TNF. In frame deletions as well as Cys-to-Ser mutations in the 14.7K gene were generated by site-directed mutagenesis and then built into the genome of a modified adenovirus type 5 (dl7001) that lacks all E3 genes. dl7001, which replicates to the same titers as does adenovirus type 5 in cultured cells, has the largest E3 deletion analyzed to date. 51Cr release was used to assay TNF cytolysis. Our results indicate that most mutations in the 14.7K gene result in a loss of function, suggesting that nearly the entire protein rather than a specific domain functions to prevent TNF cytolysis. PMID- 8445726 TI - An apoptosis-inhibiting baculovirus gene with a zinc finger-like motif. AB - Spodoptera frugiperda SF-21 cells infected with Autographa californica nuclear polyhedrosis virus mutants which lack a functional p35 gene undergo apoptosis, a type of programmed cell death. To identify p35-homologous genes in other baculoviruses, A. californica nuclear polyhedrosis virus DNA containing a deletion in p35 was cotransfected into SF-21 cells along with genomic DNAs from other baculoviruses. One of the viral DNAs which were able to rescue wild-type infection was from Cydia pomonella granulosis virus (CpGV). The CpGV gene responsible for the effect was mapped to a 1.6-kb SalI-SstI subclone of the SalI B fragment of CpGV. The sequence of the SalI-SstI subclone revealed an open reading frame capable of encoding a polypeptide of 31 kDa which was sufficient to rescue wild-type infection; this gene was thus called iap (inhibitor of apoptosis). The predicted sequence of the IAP polypeptide exhibited no significant homology to P35 but contained a zinc finger-like motif which is also found in other genes with the potential to regulate apoptosis, including several mammalian proto-oncogenes and two insect genes involved in embryonic development. In the context of the viral genome, both iap and p35 were able to block apoptosis induced by actinomycin D, indicating that these genes act by blocking cellular apoptosis rather than by preventing viral stimulation of apoptosis. Several independent recombinant viruses derived from cotransfections with either the entire CpGV genome or the 1.6-kb subclone were characterized. PMID- 8445727 TI - Nucleotide sequence of the primer RNA for DNA replication of filamentous bacteriophages. AB - We determined the nucleotide sequence of RNA synthesized in vitro by Escherichia coli RNA polymerase at the complementary-strand replication origin on the single stranded viral DNA of bacteriophages f1 and IKe (ori-RNA) by using chain terminating ribonucleoside triphosphate analogs. The results indicated that the start site of f1 ori-RNA synthesis is 20 nucleotides downstream from the site previously reported (K. Geider, E. Beck, and H. Schaller, Proc. Natl. Acad. Sci. USA 75:645-649, 1978) and that the RNA sequence [(5')pppAGGGCGAUGGCCCACUACGU OH(3')] is complementary to the f1 DNA sequence from nucleotides 5736 to 5717, with minor heterogeneity at the 3' end. IKe ori-RNA had a sequence identical to that of f1 ori-RNA, except for a single base substitution, and IKe RNA was complementary to a region of IKe DNA (from nucleotides 6441 to 6422) that was homologous to the f1 sequence. Phenotypes and ori-RNA sequences in the relevant region of the genome of f1 deletion mutants were consistent with the presently determined sequence of ori-RNA. A possibility that ori-RNA synthesis is initiated by a mechanism similar to that for general transcription is suggested as a result of the new assignment of the ori-RNA start site. The double-origin plasmid assay of minus-strand origin activity, a sensitive in vivo method for detecting cis acting elements for the initiation of DNA replication on a single-stranded DNA template, is described. PMID- 8445728 TI - Quantitation of human immunodeficiency virus type 1 infection kinetics. AB - Tissue culture infections of CD4-positive human T cells by human immunodeficiency virus type 1 (HIV-1) proceed in three stages: (i) a period following the initiation of an infection during which no detectable virus is produced; (ii) a phase in which a sharp increase followed by a peak of released progeny virions can be measured; and (iii) a final period when virus production declines. In this study, we have derived equations describing the kinetics of HIV-1 accumulation in cell culture supernatants during multiple rounds of infection. Our analyses indicated that the critical parameter affecting the kinetics of HIV-1 infection is the infection rate constant k = Inn/ti, where n is the number of infectious virions produced by one cell (about 10(2)) and ti is the time required for one complete cycle of virus infection (typically 3 to 4 days). Of particular note was our finding that the infectivity of HIV-1 during cell-to-cell transmission is 10(2) to 10(3) times greater than the infectivity of cell-free virus stocks, the inocula commonly used to initiate tissue culture infections. We also demonstrated that the slow infection kinetics of an HIV-1 tat mutant is not due to a longer replication time but reflects the small number of infectious particles produced per cycle. PMID- 8445729 TI - RNA-binding activity of hepatitis delta antigen involves two arginine-rich motifs and is required for hepatitis delta virus RNA replication. AB - Hepatitis delta antigen (HDAg) is an RNA-binding protein with binding specificity for hepatitis delta virus (HDV) RNA (J. H. Lin, M. F. Chang, S. C. Baker, S. Govindarajan, and M. M. C. Lai, J. Virol. 64:4051-4058, 1990). By amino acid sequence homology search, we have identified within its RNA-binding domain two stretches of an arginine-rich motif (ARM), which is present in many prokaryotic and eukaryotic RNA-binding proteins. The first one is KERQDHRRRKA and the second is EDEKRERRIAG, and they are separated by 29 amino acids. Deletion of either one of these ARM sequences resulted in the total loss of the in vitro RNA-binding activity of HDAg. Thus, HDAg is different from other RNA-binding proteins in that it requires two ARM-like sequences for its RNA-binding activity. Replacement of the spacer sequence between the two ARMs with a shorter stretch of sequence also reduced RNA binding in vitro. Furthermore, site-specific mutations of the basic amino acid residues in both ARMs resulted in the total loss or reduction of RNA binding activity. The biological significance of the RNA-binding activity was studied by examining the trans-activating activity of the RNA-binding mutants. The plasmids expressing HDAgs with various mutations in the RNA-binding motifs were cotransfected with a replication-defective HDV dimer cDNA construct into COS cells. It was found that all the HDAg mutants which had lost the in vitro RNA binding activity also lost the ability to complement the defect of HDV RNA replication. We conclude that the trans-activating function of HDAg requires its binding to HDV RNA. PMID- 8445730 TI - Replication of hepatitis delta virus RNA: effect of mutations of the autocatalytic cleavage sites. AB - Hepatitis delta virus (HDV) contains a circular RNA genome of 1.7 kb. HDV RNA replication is thought to proceed via a rolling-circle mechanism that is dependent on autocatalytic cleavage and ligation reactions. However, it has never been established that these ribozyme activities are indeed involved in HDV RNA replication. To investigate the possible biological significance of HDV RNA self cleavage, we constructed several HDV dimer cDNAs containing single-base substitutions of the 3' nucleotide of the genomic and the antigenomic self cleavage sites. These mutations were known to affect self-cleavage in vitro to various extents. The effects of these mutations on HDV RNA replication were examined in hepatic and nonhepatic cell lines. The results showed that all of the mutants which had lost the in vitro self-cleavage activity could not replicate. The only mutant which retained full cleavage activity replicated as efficiently as the wild-type RNA. Thus, this study established that self-cleavage activity is required for HDV RNA replication in cells. Interestingly, the level of HDV RNA detected in cells transfected with this replication-competent mutant and that detected in cells transfected with the wild-type construct were similar in COS-7 cells but vastly different in HepG2 and Huh-7 cells, suggesting that HDV RNA self cleavage activity may be modulated by cell-specific factors. We also compared the effects of mutations when the primary transcripts of these constructs were of either genomic or antigenomic sense. In constructs which synthesize primary transcripts of genomic sense, all of the antigenomic self-cleavage mutants produced as much hepatitis delta antigen (HDAg) as did the wild-type construct, even in the absence of detectable HDV RNA replication, whereas the genomic self cleavage mutants produced very little HDAg. These and other data suggest that (i) the primary HDV RNA transcripts of both genomic and antigenomic polarities must first be processed to serve as a template for HDV RNA transcription, (ii) efficient cleavage at the antigenomic self-cleavage site is not required for HDAg expression, and (iii) HDV RNA replication most likely occurs by a double-rolling circle mechanism. PMID- 8445731 TI - Requirements for incorporation of Pr160gag-pol from human immunodeficiency virus type 1 into virus-like particles. AB - The roles of the human immunodeficiency virus precursor polyproteins Pr55gag and Pr160gag-pol in viral core assembly were studied in CMT3-COS cells. To do this, the precursors were expressed separately by using a simian virus 40 late replacement vector system described previously. Consistent with previously published data, our results show that the Pr55gag precursor, when expressed alone, was able to form particles which had an immature morphology and that particle formation required the presence of a myristate addition signal at the amino terminus of the precursor. In contrast, the Pr160gag-pol precursor was not able to form particles when expressed alone, although it still underwent proteolytic processing. Coexpression of the two precursor polyproteins from separate vectors in the same cell resulted in processing of the Pr55gag in trans by the protease embedded in Pr160gag-pol and the formation of virus-like particles containing the products of both precursors. Proteolytic processing occurred independently of the presence of a functional myristate addition signal on either precursor. On the other hand, removal of myristate from one or the other precursor had nonreciprocal effects on virus particle formation. Cells expressing Pr55gag lacking myristate and Pr160gag-pol containing it did not produce particles. Cells expressing a myristylated Pr55gag and unmyristylated Pr160gag-pol still produced virus-like particles which contained nearly normal amounts of Pr160gag-pol. The results suggest that the incorporation of Pr160gag pol into particles is largely determined by intermolecular protein-protein interactions between the two precursor polypeptides. PMID- 8445732 TI - Cleavage at a novel site in the NS4A region by the yellow fever virus NS2B-3 proteinase is a prerequisite for processing at the downstream 4A/4B signalase site. AB - Flavivirus proteins are produced by co- and posttranslational proteolytic processing of a large polyprotein by both host- and virus-encoded proteinases. The viral serine proteinase, which consists of NS2B and NS3, is responsible for cleavage of at least four dibasic sites (2A/2B, 2B/3, 3/4A, and 4B/5) in the nonstructural region. Since the amino acid sequence preceding NS4B shares characteristics with signal peptides used for translocation of nascent polypeptides into the lumen of the endoplasmic reticulum, it has been proposed that cleavage at the 4A/4B site is mediated by a cellular signal peptidase. In this report, cell-free translation and in vivo transient expression assays were used to study processing in the NS4 region of the yellow fever virus polyprotein. With a construct which contained NS4B preceded by 17 residues constituting the putative signal peptide (sig4B), membrane-dependent cleavage at the 4A/4B site was demonstrated in vitro. Surprisingly, processing of NS4A-4B was not observed in cell-free translation studies, and in vivo expression of several yellow fever virus polyproteins revealed that the 4A/4B cleavage occurred only during coexpression of NS2B and the proteinase domain of NS3. Examination of mutant derivatives of the NS3 proteinase domain demonstrated that cleavage at the 4A/4B site correlated with expression of an active NS2B-3 proteinase. From these results, we propose a model in which the signalase cleavage generating the N terminus of NS4B requires a prior NS2B-3 proteinase-mediated cleavage at a novel site (called the 4A/2K site) which is conserved among flaviviruses and located 23 residues upstream of the signalase site. In support of this model, mutations at the 4A/4B signalase site did not eliminate processing in the NS4 region. In contrast, substitutions at the 4A/2K site, which were engineered to block NS2B-3 proteinase-mediated cleavage, eliminated signalase cleavage at the 4A/4B site. In addition, the size of the 3(502)-4A product generated by trans processing of a truncated polyprotein, 3(502)-5(356), was consistent with cleavage at the 4A/2K site rather than at the downstream 4A/4B signalase site. PMID- 8445733 TI - The blocks to human immunodeficiency virus type 1 Tat and Rev functions in mouse cell lines are independent. AB - Rodent cells present two blocks precluding the expression of the human immunodeficiency virus type 1 (HIV-1) genome. First, the viral protein Tat is only poorly active in these cells. Second, when the HIV-1 provirus is integrated in the genome of mouse cells, it electively fails to express the viral structural proteins, indicating a block to Rev action. Both defects can be complemented by fusion of the infected mouse cells with uninfected human cells. Because the production of high levels of Rev is dependent on Tat-mediated transactivation and because both Tat and Rev bind the viral transcript, it has been hypothesized that the two blocks found in rodent cells might be linked. In the present work, we demonstrate that overexpression of Rev in mouse cell lines does not relieve their block in HIV-1 structural-gene expression. In addition, we show that this defect is also present in human-mouse cell hybrids which contain human chromosome 12 and support Tat function. On that basis, we conclude that the blocks to HIV-1 Tat and Rev action in mouse cell lines are independent and result from the absence of distinct cellular elements that are critical for HIV-1 gene expression. PMID- 8445734 TI - The p12I, p13II, and p30II proteins encoded by human T-cell leukemia/lymphotropic virus type I open reading frames I and II are localized in three different cellular compartments. AB - Three protein isoforms are encoded by the human T-cell leukemia/lymphotropic virus type I pX region open reading frames (ORF) I and II through alternative splicing. Both the singly and doubly spliced mRNAs from ORF I encode a single 12 kDa protein (p12I), whereas two distinct proteins of 13 kDa (p13II) and 30 kDa (p30II) are encoded from the ORF II alternatively spliced mRNA. Because the p12I protein is very hydrophobic and poorly immunogenic, we genetically engineered its cDNA by adding a short stretch of amino acids from the highly immunogenic epitope HA1 of influenza virus or the AU1 epitope of bovine papillomavirus. The HA1 epitope was also added to the p13II and p30II proteins, albeit rabbit immune sera raised against synthetic peptides were also available. To determine in which cellular compartments these proteins reside, we transfected the tagged and wild type cDNAs in HeLa/Tat cells and studied their localization by indirect immunofluorescence. The p12I protein was identified in the cellular endomembranes and, particularly, in the perinuclear area. p13II and p30II were found in the nuclei and nucleoli of the transfected cells, respectively. The presence of the HA1 epitope at the carboxy terminus of p13II and p30II did not interfere with their cellular localization, since the rabbit immune sera demonstrated their presence in the same cellular compartments when the untagged proteins were expressed. The defined localization of these proteins in specific cellular compartments warrants further study of their function. PMID- 8445735 TI - Replication of Colorado tick fever virus within human hematopoietic progenitor cells. AB - Significant neutropenia, as well as thrombocytopenia and a mild anemia, occurs in patients infected with Colorado tick fever virus. In this study, human bone marrow CD34+ cells and KG-1a cells, a human hematopoietic progenitor cell line, were infected in vitro with Colorado tick fever virus. The time course and morphological appearance of viral replication in human progenitor cells were similar to those seen in erythroblasts and in HEL cells and suggest one possible mechanism for the clinical hematologic findings. PMID- 8445736 TI - The human papillomavirus E7 oncoprotein and the cellular transcription factor E2F bind to separate sites on the retinoblastoma tumor suppressor protein. AB - The ability of the high-risk and low-risk human papillomavirus E7 oncoproteins to disrupt complexes of the retinoblastoma tumor suppressor protein pRB and the cellular transcription factor E2F was studied. The ability of E7 to disrupt this transcription factor complex correlated with the different pRB binding efficiencies of the high-risk and low-risk human papillomavirus-encoded E7 proteins. The pRB binding site was the sole determinant for these observed differences. The phosphorylation status of the casein kinase II site that is immediately adjacent to the pRB binding site in E7 had no marked effect on this biochemical property of E7. Peptides consisting of the pRB binding site of E7, however, were not able to disrupt the pRB/E2F complex. These data suggest that additional carboxy-terminal sequences in E7 are also required for the efficient disruption of the pRB/E2F complex and that E7 and E2F may interact with nonidentical sites of pRB. PMID- 8445737 TI - Sequence specificity of the core-binding factor. AB - The core-binding factor (CBF) binds the conserved core motif in mammalian type C retrovirus enhancers. We analyzed the phosphate contacts made by CBF on the Moloney murine leukemia virus enhancer by ethylation interference assay. The phosphate contacts span 9 bp centered around the consensus core site. To examine the sequence preferences for CBF binding, we employed the technique of selected and amplified binding sequence footprinting (T. K. Blackwell and H. Weintraub, Science 250:1104-1110, 1990). The consensus binding site for CBF defined by selected and amplified binding sequence footprinting is PyGPyG GTPy. PMID- 8445739 TI - Nucleotide sequence and transcriptional analysis of a gene encoding gp41, a structural glycoprotein of the baculovirus Autographa californica nuclear polyhedrosis virus. PMID- 8445738 TI - Localization of the c-ets-2 transactivation domain. AB - The human ets-2 proto-oncogene is one of the homologs of the v-ets gene, found in avian acutely transforming retrovirus E26 (D. Leprince, A. Gegonne, J. Call, C. de Taisne, A. Schneeberger, C. Lagrou, and D. Stehelin, Nature [London] 306:395 397, 1983; M. F. Nunn, P. H. Seeburg, C. Moscovici, and P. H. Duesberg, Nature [London] 306:391-395, 1983), which causes leukemia in chickens. We used the DNA binding domain of yeast transcriptional activator GAL4 to locate the transactivation region of human ets-2. The transactivation domain of ets-2 was found in the N-terminal part of the protein, which is homologous to ets-1, and can be disrupted by deletion of a stretch of acidic amino acid residues. A transactivation-deficient mutant of ets-2 failed to transform Rat-1 cells and suppressed the transforming activity of coexpressed wild-type ets-2. A mutation in the putative DNA-binding region of ets-2 abolished transforming activity. We show that the motif crucial for ets-2 transactivation capability is necessary for transforming activity in Rat-1 cells. Mutant ets-2 protein that lacks the transactivation domain has a dominant negative effect on transformation by wild type ets-2. We were unable to detect ets-2-dependent transcriptional regulation of several enhancers containing ets-binding motifs. PMID- 8445740 TI - Observations on the calf venous pump mechanism: determinants of postexercise pressure. AB - PURPOSE: We investigated the factors determining postexercise pressure and the relationship of venous valve closure and venous column segmentation to ambulatory venous pressure changes. METHODS: Valve closure and venous segmentation were observed during dynamic ascending phlebography in 40 nonrefluxive limbs and by duplex imaging in 25 normal limbs in healthy volunteers. Simultaneous volume (air plethysmography) and pressure studies during calf exercise were also carried out. Some studies used a simple mechanical model comprised of a collapsible latex tube ("calf pump") and a graduated "popliteal" valve. RESULTS: The femoropopliteal venous column above the popliteal valve remains unsegmented and continuous during ambulatory venous pressure changes in response to calf muscle contraction. Therefore ambulatory venous pressure changes cannot be explained purely on the basis of hydrostatic column pressure changes. Postexercise pressure appears to be determined by a complex set of factors: (1) physical segmentation of the venous column below the popliteal valve (i.e., tibial valve closure); (2) tube collapse below the closed valve, which further aids in the breakup of the hydrostatic column pressure and dampens the effect of any reflux through or around the closed valve; (3) ejection fraction, which influences the degree of tube collapse; and (4) the interaction of the resultant pressure forces with the wall properties of the venous pump. CONCLUSIONS: The mechanism of ambulatory venous pressure reduction is complex and multifactorial. The importance of venous wall characteristics as a determinant of postexercise pressure has not been previously appreciated. Changes in venous wall property after a thrombotic process, for example, could conceivably influence ambulatory venous pressure and recovery time in the absence of reflux. PMID- 8445741 TI - Age determination of experimental venous thrombi by ultrasonic tissue characterization. AB - PURPOSE: The ability of ultrasonic tissue characterization based on radiofrequency signal processing to detect compositional differences in thrombi of varying ages was evaluated in vivo. METHODS: Thrombi were produced in 49 jugular veins of 26 anesthetized 18 to 20 kg pigs by partial ligation and application of direct electric current. Thrombi were imaged 30 minutes after formation and 1, 7, and 14 days later with a color Doppler ultrasound scanner that identified the thrombi, and acquired radio frequency data for ultrasonic tissue characterization analysis. Ultrasonic tissue characterization used two parameters from the normalized power spectrum, slope, and intercept, which are related to scatterer size, scatterer concentration, and acoustic-impedance differences between scatterers and surrounding medium. Previous in vitro studies demonstrated that lower slope and higher intercept values correlated with greater cellularity and more-dense fibrin mesh. Histologic examination was performed for each time period. The values of slope and intercept for each timed observation were compared by a multilinear discriminant analysis. RESULTS: There were no statistical differences between day 0 and day 1. Statistically-significant differences in ultrasonic tissue characterization parameters were seen between all other time intervals with p values < 0.01. Older thrombi tended to demonstrate higher slope and lower intercept values. These ultrasonic tissue characterization changes correlated with a red cell and fibrin-mesh density reduction, which was confirmed by histologic findings and was indicative of partial spontaneous thrombolysis. The degree of spontaneous thrombolysis provides an estimate of the age of thrombi. CONCLUSION: Ultrasonic tissue characterization is capable of distinguishing age differences in thrombi in an animal model and has the potential for noninvasive application in clinical diagnosis. PMID- 8445742 TI - Reactive hyperemia test in a random sample of the general population. AB - PURPOSE: The purpose of this article is to determine the performance of a reactive hyperemia test in the general population in terms of validity, increase in case identification, and test refusal; and to identify differences between the two major ways of expressing the results (the postocclusive ankle index and the percentage change in ankle systolic pressure). METHODS: Changes in ankle pressures were measured during reactive hyperemia in 1460 men and women aged 55 to 74 years, who were randomly sampled in the Edinburgh Artery Study. The validity of the test was determined in 91 cases identified by the presence of intermittent claudication and a low resting ankle pressure and in 91 controls matched by age and sex. RESULTS: The mean postocclusive ankle index was 0.98 (SD 0.20), and the mean drop in ankle pressure was 9.89% (SD 12.79%). In examining the validity of the test, differences occurred in the two ways of expressing the results: the postocclusive ankle index was 90% sensitive and 97% specific and the percentage drop in ankle pressure was 52% sensitive and 86% specific in detecting disease. The postocclusive ankle index increased the overall identification of cases in the Edinburgh Artery Study from 6.5% to 11.5%, but the percentage drop in ankle pressure increased identification to only 9.5%. Eight percent of subjects refused the test because of discomfort; this group contained more women, more elderly, and more obese subjects. CONCLUSIONS: The reactive hyperemia test is an appropriate test to use in the general population. The results are more accurate when expressed as the postocclusive ankle index rather than the percentage drop in ankle pressure. PMID- 8445743 TI - Venous ulcers and the superficial venous system. AB - PURPOSE: The purpose of this study is to identify the anatomic location of venous disease in patients with venous ulceration and chronic venous insufficiency. METHODS: Both limbs of 59 consecutive patients attending the Middlesex Hospital Vascular Laboratory (London, U.K.) with venous ulceration were assessed by color duplex ultrasound scanning to determine the location of venous disease. RESULTS: Isolated deep venous reflux was present in only 12 limbs (15%). A combination of deep and superficial venous reflux was found in 25 limbs (32%), and in 42 limbs (53%) there was only superficial venous reflux. CONCLUSION: In just over half the patients with venous ulceration, the disease is confined to the superficial venous system. This group of patients may benefit from surgical treatment. This study emphasizes the need for vascular laboratory investigation of patients with leg ulceration. PMID- 8445744 TI - Reconstruction of the ligated external carotid artery for embolization of cervicofacial arteriovenous malformations. AB - PURPOSE: Until recently, the accepted management of life-threatening complications of unresectable cervicofacial arteriovenous malformations (AVMs) has been ligation of the major feeding vessels, usually the branches or the main trunk of the external carotid artery. Rapid enlargement of collateral vessels around the ligature is usually associated with an early return of symptoms. Percutaneous transcatheter embolization of the nidus of the arteriovenous malformation is now the preferred treatment for symptomatic AVMs that cannot be excised. Previous ligation of the main feeding vessels prevents catheter access and embolization therapy of the lesion. The purpose of this report is to describe our experience with the treatment of patients with symptomatic unresectable cervicofacial AVMs and previous external carotid artery ligation. METHODS: Six patients with symptoms from cervicofacial arteriovenous malformations required surgical reconstruction of their previously ligated external carotid artery with the anticipation of catheter embolization therapy to the branch vessels feeding the malformation. Saphenous vein was used in five reconstructions; a polytetrafluoroethylene graft was used in one. RESULTS: After successful arterial reconstruction, massive swelling of the tongue and perioral tissue developed in two patients, which necessitated tracheostomy in one patient; and embolization therapy before extubation could be safely performed in the other patient. In all, four patients underwent successful embolization therapy. One refused subsequent treatment. In one patient with severe epistaxis, external carotid artery revascularization led to the healing of the nasal ulcers without need for embolization therapy. CONCLUSIONS: For patients with previous ligations of the external carotid artery and symptomatic AVMs, revascularization of the external carotid artery is an important step in treatment. The surgery must be carefully coordinated with the interventional radiologist for possible emergency postoperative embolization therapy. External carotid artery ligation only complicates the treatment of patients with cervicofacial AVMs, and should no longer be used in the treatment of these individuals. PMID- 8445745 TI - In vitro construction of a human blood vessel from cultured vascular cells: a morphologic study. AB - PURPOSE: The purpose of this study was to create a tubular vascular model exclusively made of human cells and collagen. METHODS: The blood vessel equivalent was constructed with the three following human cell types: vascular smooth muscle cells, endothelial cells, and fibroblasts. A tissuelike structure was obtained from the contraction of a tubular collagen gel (human origin) by vascular smooth muscle cells, which created a media-like structure. An adventitia like tissue was added around the media-like structure by embedding fibroblasts into a collagen gel. An endothelium was established within the tubular structure after intraluminal cell seeding. RESULTS: Cell orientation and gel contraction were followed up over time. Vascular smooth muscle cells developed a complex tridimensional network and were oriented in a circular fashion around the tube's axis. In contrast, fibroblasts were randomly oriented. A viable, homogeneous, and well-characterized endothelium was observed. These endothelial cells showed a slightly elongated structure and were oriented parallel to this vascular equivalent axis. CONCLUSION: An in vitro tridimensional vascular model that exhibits some phenotypic characteristics of in vivo vascular cells could be useful in the study of events that lead to atherosclerotic plaque formations. PMID- 8445746 TI - Accuracy and reproducibility of duplex ultrasonography in grading femoropopliteal stenoses. AB - PURPOSE: The aim of this study was to determine the accuracy of Doppler waveform characteristics in grading femoropopliteal stenoses and to determine the interobserver and intraobserver reproducibility of measuring the same waveform characteristics. METHODS: Thirty patients with isolated areas of stenosis found by arteriography were evaluated by color duplex sonography. Each patient underwent scanning by two observers on two separate occasions. Each observer was blind to the other's results. Doppler spectra were recorded in areas where color change suggested the highest velocity and also at the nearest normal proximal area. Peak systolic velocity, spectral broadening, and waveform configuration were measured at each site. RESULTS: An increase in peak systolic velocity of more than 200% accurately predicted a 50% or greater reduction in luminal diameter on angiography (70% sensitivity, 96% specificity). The presence of spectral broadening and an abnormal waveform shape were found to correlate poorly with the degree of stenosis. Analysis of variance showed no significant difference between observers in velocity measurements (p = 0.78). CONCLUSIONS: We conclude that although stenoses of greater than 50% can be distinguished from minor stenoses, more precise definition of the degree of narrowing is unlikely. The good repeatability of the velocity ratio makes it an excellent tool for monitoring major changes in the progression of disease. PMID- 8445747 TI - Thromboembolic complications of polycythemia: polycythemia vera versus smokers' polycythemia. AB - PURPOSE: This report compares patients with the hypercoagulable state of polycythemia vera to patients with secondary polycythemia caused by tobacco use to determine whether the incidence of thromboembolic events is equivalent. METHODS: The medical records of 146 patients with the diagnosis of polycythemia between 1977 to 1990 were reviewed. Patients with transient, relative, or stress polycythemia were excluded from this study as were patients with polycythemia as a result of cardiac or pulmonary anomalies or both. The diagnosis of polycythemia vera (n = 43) was verified by use of the guidelines of the Polycythemia Vera Study Group. The diagnosis of polycythemia caused by smoking (n = 27) was based on an elevated total red blood cell volume, decreased oxygen saturation on arterial blood gas measurement, evidence of chronic obstructive pulmonary disease, and elevated carboxyhemoglobin levels. RESULTS: Twenty-six patients (60%) with polycythemia vera and 11 patients (41%) with smoker's polycythemia had at least one thromboembolic problem. No significant differences existed between the groups with regard to age, hematocrit, or number of cardiac and cerebrovascular events. Overall, patients with polycythemia vera had a greater number of thromboembolic events per patient (p < 0.05) and more peripheral arterial thromboemboli (p < 0.005) than did patients with polycythemia as a result of smoking (Fisher's Exact Test). CONCLUSIONS: Thus the results of this study demonstrate that smokers' polycythemia does not represent a hypercoagulable state equivalent to that of polycythemia vera. PMID- 8445748 TI - Accuracy and reproducibility of duplex ultrasound imaging in a phantom model of femoral artery stenosis. AB - PURPOSE: The improvement of management strategies in patients with intermittent claudication might depend on a better understanding of the natural history of femoral atherosclerosis. The grading of stenoses, the monitoring of their progression, and the assessment of response to treatment are critically dependent on a method's accuracy and variability. Duplex ultrasound imaging provides a noninvasive way of measuring localized disease, but there has been relatively little objective evaluation of its accuracy and reproducibility. The aim of this study was to evaluate the accuracy and variability of duplex velocity ratio measurements of stenosis. METHODS: In a laboratory flow model of the femoral artery, 14 concentric and eccentric stenoses were examined five times by three sonographers. Measurements were then repeated with a standardized technique in which Doppler angle and aperture position were fixed, giving a total of 420 measurements. RESULTS: Velocity ratio showed good correlation with degree of stenosis, R2 = 0.996. Intraobserver variability was low, but interobserver variability was significant with more severe stenosis (p = 0.002, analysis of variance). Standardization of the technique did not improve accuracy or variability. The 95% confidence limit was +/- 20% for a single reading of velocity ratio for stenoses of > 50% diameter reduction. CONCLUSIONS: We conclude that duplex ultrasound imaging can be used to accurately grade arterial stenosis in this range, and the potential exists for noninvasive monitoring of the progression of preocclusive femoral atherosclerosis and its response to treatment. In addition, repeated measurements of velocity ratio over time should be made by the same observer. PMID- 8445749 TI - Differential stimulation of macrophage procoagulant activity by vascular grafts. AB - PURPOSE: The mechanism by which some graft materials are more thrombogenic than others is poorly understood. We hypothesized that differential induction of macrophage procoagulant activity (PCA) by various materials may contribute to variable thrombogenicity. METHODS: Thioglycollate-elicited murine peritoneal macrophages were added to disks of Dacron and expanded polytetrafluoroethylene (ePTFE). After adherence, macrophages were incubated with and without endotoxin (lipopolysaccharide) and then recovered by sonication for determination of PCA with a one-step clotting bioassay. RESULTS: PCA was significantly higher in cells after incubation on Dacron compared with ePTFE both in the absence of lipopolysaccharide (243 +/- 76 vs 68 +/- 39 mU, n = 4) and after stimulation with lipopolysaccharide (491 +/- 137 vs 139 +/- 41 mU, n = 4) (p < 0.01, analysis of variance). Using factor-deficient plasmas, we found that this PCA was consistent with tissue factor. This differential induction of PCA was related to increased macrophage adherence to Dacron compared to that to ePTFE (9374 +/- 1158 vs 2111 +/- 330 cells/mm2; n = 4; p < 0.01, analysis of variance). CONCLUSIONS: The thrombogenic nature of Dacron correlates with its ability to adhere macrophages and induce PCA. Strategies aimed at modulating these effects may reduce the thrombogenicity of vascular grafts and therefore potentially the incidence of graft thrombosis. PMID- 8445750 TI - Comparative in vivo study on the healing qualities of four different presealed vascular prostheses. AB - PURPOSE: The purpose of this article is to assess the healing qualities of presealed knitted polyester prostheses. METHODS: Thoracic aortic replacement was performed with grafts with four different coating materials-collagen (CP), albumin (AP), and two with gelatin (GP1/GP2)-in four groups of 15 pigs each. Two weeks, 6 weeks, and 6 months after operation, five pigs of each group were killed. Healing quality was assessed by morphometric analysis of the remaining coating, the extent of tissue ingrowth, and the thickness of the inner layer. RESULTS: The sealant was rapidly absorbed in all prostheses except for the AP (remaining coating at 2 weeks: GP1 22.1%, GP2 34.7%, and CP 68.0% vs AP 97.1% [p < 0.05]), remaining coating at 6 weeks: GP1/GP2 0% and CP 2.5% vs AP 76.7% (p < .01). At 6 months, remaining coating was only detectable in AP (21.5%). At 2 weeks the extent of tissue ingrowth ranged from 65.7% in GP1 and 75.3% in CP to 80% in GP2 versus 8.9% in AP (p < 0.05). There was a slow increase of tissue ingrowth until the sixth postoperative week (GP1 74.4%, GP2 85.0%, and CP 91.3% versus AP 19.6% [p < 0.01]). Thickness of the internal layer varied from 0.11 to 0.21 mm at 2 weeks in all grafts studied and from 1.02 mm (AP) and 1.28 mm (GP2) to 1.39 mm (GP1), versus 0.41 mm in the CP (p < 0.01) after 6 months of implantation. CONCLUSIONS: The type of coating significantly influences the healing properties of knitted polyester prostheses. When used for thoracic aortic replacement in pigs, AP coating clearly results in inferior healing compared with GP1/GP2 or CP impregnation, with digestion of the coating material and tissue ingrowth used as parameters. The thinnest internal layer was found in the CP prostheses, reflecting superior healing properties of this coating in the model studied. PMID- 8445751 TI - Partial replacement of an infected arterial graft by a new prosthetic polytetrafluoroethylene segment: a new therapeutic option. AB - PURPOSE: As the title suggests, this is an account of treating infected arterial grafts other than by the accepted methods of complete graft removal and revascularization with autogenous material or extraanatomic bypass. METHODS: Since 1973, 42 patients with infected arterial grafts (n = 35) or autogenous reconstructions (n = 7) were seen with false aneurysm, hemorrhage, or perigraft or perianastomotic pus and were treated by removal of the infected graft and immediate adjacent or in situ revascularization by polytetrafluoroethylene (PTFE) in 39 cases and Dacron in three cases. Management plan included (1) removal of only the obviously infected part of the original graft, (2) obliteration of the infected anastomotic site, and (3) placement of the new PTFE graft in an adjacent clean or debrided route. So treated were 15 aortic Dacron grafts, 20 PTFE grafts (2 iliofemoral, 3 femorofemoral, and 15 femorodistal), and 7 autogenous reconstructions with bleeding. Partial graft salvage was attempted in 10 of 15 Dacron and 19 of 20 PTFE grafts. RESULTS: Four patients required further removal of the original infected graft (three Dacron, one PTFE), giving an ultimate success rate of 7 of 15 Dacron and 18 of 20 PTFE grafts; two patients required further obliteration of the original adjacent infected arterial segment because of rebleeding. An additional PTFE segment was joined successfully to incorporated PTFE in all six repeat operations. Initial failure did not prejudice the outcome; direct arterial flow to at least midthigh level was preserved in 37 of the 42 patients for a mean period of 40 months (range 9 to 130 months). Three of the new PTFE grafts occluded and became infected, which led to amputation and one death at a secondary operation. Visceral complications caused the only two other deaths in the aortic group. Five late amputations (four below the knee and one above the knee) were required because of femorodistal graft occlusion. CONCLUSIONS: Partial removal of infected grafts with adjacent or in situ replacement by PTFE is possible, simplifies management, and permits maintenance of distal circulation with low morbidity and mortality rates. PMID- 8445752 TI - Duplex scanning of the inferior epigastric artery. AB - PURPOSE: The inferior epigastric artery (IEGA) has been used as a conduit for coronary artery bypass grafting. Because of varying lengths, diameters, and depths, a method of determining vessel adequacy before operation was needed. METHOD: A BioSound Phase II scanner (BioSound, Indianapolis, Ind.) with a 10 MHz probe was used to image the IEGA in 40 patients. Beginning at the common femoral artery and moving superiorly, the external iliac artery is identified with its first branch, which is the IEGA. The IEGA is located deep in the rectus muscle, along the posterior rectus sheath. Frequent measurements of the diameter and depth are taken along the length of the IEGA. RESULTS: When comparing the group of patients in whom there was operative confirmation of the ultrasound findings, we found, on the right side, a mean length of 9.0 cm and mean diameter of 2.4 mm by ultrasonography and 10.5 mm and 2.4 mm at operation. On the left side the findings were 9.6 cm and 2.6 mm by ultrasonography and 11 cm and 2.6 mm at operation. There was one wound complication in an IEGA harvest site that had a body wall thickness of less than 4 cm (1/23; 4.2%), but all four sites with a body wall thickness of 4 cm or greater developed wound complications (4/4; 100%). CONCLUSION: The use of duplex scanning of the IEGA before operation provided excellent information about the length, diameter, depth, and patency of the vessel. Preoperative scanning prevented unnecessary dissection when the IEGA was not of adequate length or diameter. It was also very useful in providing information regarding risk of wound complications in obese patients. PMID- 8445753 TI - Differential response of arteries and vein grafts to blood flow reduction. AB - PURPOSE: This study was undertaken to evaluate the effect of blood flow on the dimensions and cellular composition of normal arteries and freshly placed vein grafts (VG). METHODS: Bilateral jugular vein interposition grafts were placed in the common carotid arteries of 12 New Zealand white rabbits, and blood flow was reduced on one side by external carotid artery ligation. Shear stress, tangential stress, vessel dimensions, and smooth muscle cell (SMC) proliferation of reduced flow arteries and VG were compared with these measures in contralateral controls (CON). RESULTS: A sustained reduction in blood flow was documented at 4 weeks (13 +/- 4 ml/min reduced-flow vs 21 +/- 4 ml/min CON; p < 0.05). Reduced-flow carotid arteries had a smaller lumen radius and greater medial thickness compared with normal-flow arteries, but there was no difference in medial cross-sectional area or medial SMC volume and no differences in any intimal measurements. These changes resulted in normalization of shear stress (15.2 +/- 4.6 dynes/cm2 reduced flow vs 13.6 +/- 2.5 dynes/cm2 CON; p = NS). All VG underwent a marked postimplantation hyperplasia in intima and media, but the major effect of flow reduction on VG dimensions occurred in the intima. Intimal thickness in reduced flow VG was 60% greater than that in control VG (57 +/- 12 microns vs 35 +/- 5 microns; p = 0.05), and intimal area was 70% greater than that in controls (0.83 +/- 0.24 microns 2 vs 0.48 +/- 0.08 microns 2; p > 0.05). Smaller differences were found in medial thickness (74 +/- 4 microns reduced-flow vs 63 +/- 4 microns CON; p = 0.02) and medial area (1.03 +/- 0.36 microns 2 reduced-flow vs 0.84 +/- 0.22 microns 2 CON; p = 0.05). Intimal SMC volume in reduced-flow VG was 37% greater than that in control VG (p = 0.07). Tangential stress in VG equaled that in ipsilateral arteries, whereas shear stress in VG remained much lower than that in arteries. CONCLUSIONS: In this model, arteries and VG responded to flow reduction by wall thickening, but the mechanism differed. Arteries underwent medial remodeling, lumen caliber reduction, and shear stress normalization, whereas VG responded by an upward modulation of the proliferative response that follows graft placement. These data support a primary role for tangential stress and a secondary role for shear stress in determination of VG dimensions. PMID- 8445754 TI - Color-flow duplex-directed manual occlusion of femoral false aneurysms. AB - PURPOSE: During the past 14 months we conducted a prospective clinical trial to evaluate the efficacy of duplex-directed manual occlusion (DDMO) of iatrogenic femoral false aneurysms (FFAs) as an alternative to standard operative management. METHODS: In all cases DDMO was performed with real-time color-flow imaging while steady, continuous external pressure was applied manually to the neck of the FFA by an experienced vascular technologist for a period of 10 minutes. RESULTS: Ten of the 11 FFAs treated with DDMO in this series were thrombosed successfully, requiring a mean of 30 minutes of compression per aneurysm (three compressions of 10 minutes each). DDMO was unsuccessful in one patient, whose session was terminated because of severe discomfort as a result of the procedure. All 10 patients with successfully thrombosed FFAs are without recurrence at 1-month follow-up color-flow duplex examination, and there has been no morbidity attributable to DDMO. CONCLUSIONS: We conclude that DDMO of postcatheterization FFA can be performed safely and is an inexpensive, effective, nonoperative method of managing such lesions. The precise role of this technique would appear to be as a first-line treatment for uncomplicated iatrogenic FFAs. PMID- 8445755 TI - Noninvasive localization of arterial occlusive disease: a comparison of segmental Doppler pressures and arterial duplex mapping. AB - PURPOSE: The purpose of this study was to compare the abilities of arterial duplex mapping and segmental Doppler pressures to noninvasively localize hemodynamically significant lower extremity arterial occlusive disease. METHODS: After angiographic controls were instituted, arterial duplex mapping and segmental Doppler pressures were blindly compared for their ability to localize a high-grade (50% to 100%) stenosis to the iliac or common femoral arteries, the superficial femoral artery, or the popliteal artery in 151 lower extremities from 79 patients. RESULTS: Rates of sensitivity and specificity of arterial duplex mapping for identifying a high-grade stenosis at the three arterial levels were 88% and 97%, 95% and 100%, and 78% and 99%, respectively. Those for segmental Doppler pressures were 59% and 86%, 73% and 80%, and 48% and 53%, respectively. There was complete agreement between arterial duplex mapping and angiography in 82% of the limbs studied and between segmental pressures and angiography in 34% of the limbs (p < 0.0001). The presence of diabetes, kidney failure, or previous vascular surgery in the limb studied did not affect the accuracy of either test. CONCLUSION: Arterial duplex mapping is far superior to segmental Doppler pressures for localization of high-grade angiographic lesions from the iliac to the popliteal arteries. PMID- 8445756 TI - Detection of outflow obstruction in chronic venous insufficiency. AB - PURPOSE: This study compares three different modes for measuring hemodynamically significant outflow obstruction in chronic venous insufficiency: (1) arm-foot venous pressure differential combined with foot venous pressure elevation to reactive hyperemia, (2) outflow fraction determination with plethysmography, and (3) calculation of resistance from simultaneously obtained foot venous pressure and calf volume curves. METHODS: The three techniques were compared in 15 normal limbs and 19 limbs with documented previous deep venous thrombosis. Outflow fraction and resistance were also measured after reactive hyperemia was induced. RESULTS: The arm-foot venous pressure measurements delineated patients with grades 1 through 4 obstruction (Raju's grading). Resistance calculations correlated well with this grading except in patients with severe grade 4 obstruction, in whom low resistance was found. Outflow fraction determinations had marked overlapping between the different obstruction grades, substantially decreasing sensitivity to detect hemodynamically important outflow obstructions. No correlation with the resistance calculations was shown. Inducing reactive hyperemia did not alleviate these findings. The failure of the outflow fraction and resistance methods to detect significant obstruction is probably attributable to the use of plethysmographic techniques for volume measurement, which appears to give false-negative results as a result of a regional volume shift within the lower limb. CONCLUSIONS: The combination of the arm-foot vein pressure differential and the foot vein pressure elevation after reactive hyperemia seems to be the only reliable test currently available for detecting and grading global chronic obstruction. PMID- 8445757 TI - A rational approach to detection of significant reflux with duplex Doppler scanning and air plethysmography. AB - PURPOSE: Several techniques are currently available for the detection of venous reflux. We have attempted to determine the relative value and accuracy of available techniques to develop a logical strategy of investigation in reflux venous insufficiency. METHODS: The morphologic distribution of venous incompetence (erect duplex and descending venography); the results of ambulatory venous pressure measurement, venous refilling time, the Valsalva test, and air plethysmography (venous refilling index, VFI); and the clinical severity were described in 118 consecutive limbs. In an attempt to validate the tests, results were correlated with the clinical severity classification (class 0, n = 34; class 1, n = 42; class 2, n = 11; class 3, n = 31) and with a standardized quantification of reflux (multisegment score) as seen on standing duplex Doppler scanning with rapid deflation cuffs. RESULTS: Twenty-nine percent of limbs with severe venous disease (class 2/3) had pure deep insufficiency, only 6% had pure superficial disease, and the remainder had a combination. A history of previous thrombosis and the presence of posterior tibial vein incompetence were markedly common with ulcer disease (84% and 42%, respectively). The duplex Doppler multisegment score correlated strongly with clinical severity classification (r = 0.97). The venous refilling time and VFI had the highest sensitivity in identifying severe venous disease (class 2/3), and the ambulatory venous pressure had excellent specificity. CONCLUSIONS: For noninvasive determination of reflux, the combination of VFI and duplex scanning not only localized reflux but also separated severe clinical vein disease from mild, with high sensitivity and specificity. Air plethysmography may also provide valuable information regarding calf muscle pump and outflow obstruction. PMID- 8445758 TI - Ultrasound measurement of the luminal diameter of the abdominal aorta and iliac arteries in patients without vascular disease. AB - PURPOSE: The purpose of this study was to establish ultrasonographic criteria for the normal size of the abdominal aorta and iliac arteries in patients without vascular disease. METHODS: The luminal diameters of the proximal and distal abdominal aorta and the common iliac arteries were measured by ultrasonography in 160 patients (15 to 89 years) who were without known vascular disease. RESULTS: In patients above 50 years of age the distal aorta, which most often is involved in aneurysmatic dilations, measured 16.8 +/- 2.9 mm in men and 14.6 +/- 1.9 mm in women (p < 0.001). The diameter of the iliac artery in these patients was 10.1 +/ 2.0 mm in men and 9.2 +/- 1.3 mm in women (p < 0.001). The usually present gradual narrowing of the aorta toward the bifurcation was replaced by a slight increase (1 to 2 mm) in 5% of the men and 6% of the women. Focal areas of aortic enlargement, however, were not observed. In multivariate analysis, including age, height, body weight, and sex, the distal aortic diameter was significantly correlated only to age (r = 0.46; p < 0.001) and sex (r = -0.29; p < 0.001). With aging the mean of the proximal and distal aortic diameters increased by 0.08 and 0.05 mm/yr, respectively. Also correlated with age was a linear reduction in systolic expansion (r = -0.73; p < 0.001). CONCLUSIONS: Enlargement of the distal aorta and common iliac artery should be considered when (1) the luminal diameters in men exceed 23 and 14 mm, respectively, and in women 19 and 12 mm, respectively, (2) the ratio of the proximal and distal aortic diameter exceeds 1.1, and (3) there is demonstration of focal enlargement. PMID- 8445759 TI - Splenic infarction after splenorenal arterial bypass. AB - Because of the spleen's extensive collateral circulation, the risk of splenic infarction after splenorenal arterial bypass (SRB) has been considered negligible. We report four patients in whom splenic infarctions developed after SRB. Splenic infarction developed in one patient at the time of SRB, and symptoms of splenic abscess (fever, abdominal pain, and leukocytosis) that proved to be splenic infarctions at laparotomy developed in three patients 2 to 16 days after the operation. Factors possibly contributing to splenic infarction could be determined for three patients. These included interruption of collateral vessels, intraoperative hypotension and disseminated intravascular coagulation, and distal splenic artery ligation. Normal Doppler flow was detected in the splenic parenchyma during test occlusions of the splenic artery before SRB in three patients. Our experience suggests that existing collateral circulation may not always sustain splenic viability after SRB, and some patients may not be suitable candidates for this operation. Factors such as adequacy of inflow, splenic artery length, and risk of perioperative hypotension should be considered. PMID- 8445760 TI - Vascular graft infection caused by Aspergillus species: case report and review of the literature. AB - We report an unusual case of vascular graft infection caused by Aspergillus fumigatus that began with a false aneurysm, major arterial emboli, and septic arthritis. Successful treatment included resection of the infected graft, restoration of circulation by extraanatomic bypass, and administration of amphotericin B and itraconazole, a new antifungal agent. Graft infection in the case reported herein most likely occurred during surgery and took place during an insidious outbreak of postoperative infection. PMID- 8445761 TI - Temporary perfusion of a congenital pelvic kidney during abdominal aortic aneurysm repair. AB - A patient with a large abdominal aortic aneurysm was noted to have a congenital pelvic kidney. The patient also had bilateral iliac aneurysms that required repair. The blood supply of the congenital pelvic kidney was not apparent from preoperative studies but was found at the time of surgery to be from the area of the aortic bifurcation. Pelvic renal ischemia was limited by a "double proximal clamping" technique and by placement of a temporary shunt from the body of the aortic graft into the pelvic renal artery during completion of two distal anastomoses. The patient's renal function remained normal during the perioperative period, and the reconstruction was demonstrated to be patent more than one year after surgery. Although simple clamping and expeditious reconstruction are appropriate in most cases of aortic surgery in the presence of congenital or transplant pelvic kidney, more complex anatomy, including iliac aneurysms, may require longer periods of ischemia. Pelvic renal ischemia may be limited with the technique described. PMID- 8445763 TI - Provoked compliance of the supernormal popliteal vein. PMID- 8445762 TI - Abdominal aortoiliac aneurysm with spontaneous aortocaval fistula: an unusual cause of acute occlusion of the inferior vena cava. PMID- 8445764 TI - Obstruction of inferior vena cava resulting from metastatic adenocarcinoma of the colon. PMID- 8445765 TI - Carotid artery imaging with computed tomography angiography. PMID- 8445766 TI - Controversies in the management of ruptured abdominal aortic aneurysm. PMID- 8445767 TI - Age-dependent changes in plasma and brain cholinesterase activities of eastern bluebirds and European starlings. AB - Age-dependent changes in plasma and brain cholinesterase (ChE) activity were characterized in two altricial passerine species: eastern bluebirds (Sialia sialis) and European starlings (Sturnus vulgaris). Plasma acetylcholinesterase (AChE) activity declined rapidly immediately after hatching, while plasma butyrylcholinesterase (BChE) activity increased throughout the nestling period. These patterns continued after birds fledged, since the BChE: AChE ratio was higher in adult birds than fledglings. This is the first confirmation of age dependent changes in plasma ChE activity in altricial species. Total plasma ChE activity increased with age in both species, which is the reverse of results previously reported for several precocial species. Brain ChE activity increased with age in both species, and did not reach asymptotic levels before young fledged. This corresponded with patterns previously documented in European starlings and three other altricial species. We propose that age and degree of precocity in young birds must be considered when examining sensitivity or evaluating field exposure of birds to ChE-inhibiting compounds. PMID- 8445768 TI - Histological investigations on the thyroid glands of marine mammals (Phoca vitulina, Phocoena phocoena) and the possible implications of marine pollution. AB - In 1988 and 1989, thousands of harbor seals (Phoca vitulina) died in the North Sea from phocine distemper infection. The morphology of thyroid glands from 40 harbor seals found dead on the North Sea coastlines of Schleswig-Holstein, Federal Republic of Germany, during an epizootic of phocine distemper, was compared with the morphology of thyroid glands from five healthy harbor seals collected in Iceland. Thyroid glands from seven harbor porpoises (Phocoena phocoena) found dead in 1990 on the North Sea coastlines also were evaluated. Colloid depletion and fibrosis were found in the thyroid glands of harbor seals which died during the epizootic, but not in animals from Iceland. Thyroid glands of the porpoises showed similar lesions, but to a lesser degree, than those observed in the North Sea seals. PMID- 8445769 TI - Phocine distemper in a harp seal (Phoca groenlandica) from the Gulf of St. Lawrence, Canada. AB - The first case of phocine distemper in a seal from Canadian waters and the first case of clinical phocine distemper in a harp seal, Phoca groenlandica, is reported. A two-month-old female harp seal stranded on Prince Edward Island in May 1991. Significant clinical findings were lethargy and severe conjunctivitis. Pulmonary congestion was the main necropsy finding, and histological lesions included diffuse demyelinating nonsuppurative encephalitis and mild multifocal interstitial pneumonia. Acidophilic intracytoplasmic and intranuclear inclusions were present in cerebral neurons and astrocytes. Immunoperoxidase staining confirmed phocine distemper virus (PDV) antigen in the cytoplasm and nuclei of neurons, bronchiolar gland epithelium and transitional epithelium of the bladder. Infectivity titers of canine distemper virus (CDV) (Onderstpoort strain) and a morbillivirus isolated from a grey seal were significantly reduced by serum from the harp seal. PMID- 8445770 TI - Brucellosis in free-ranging bison (Bison bison) from Teton County, Wyoming. AB - Brucellosis was studied opportunistically in bison (Bison bison) in the free ranging Jackson herd of approximately 120 in Teton County, Wyoming (USA) in March 1989. Recent abortion was diagnosed in a 2-yr-old cow and Brucella abortus biovar 1 was isolated from vaginal discharge, uterine contents, uterus, and supramammary lymph nodes. Endometritis was characterized by lymphoplasmacytic infiltrates in the lamina propria and neutrophils in uterine glands and within necrotic debris and exudate in the uterine lumen. A 5-yr-old bull had diffuse lymphoplasmacytic infiltrates in epididymis and accessory sex glands; B. abortus was isolated from seminal vesicle and ampulla. Twenty-seven (77%) of 35 bison tested from 1989 to 1990 were serologically positive or suspect on tests for Brucella antibodies. We report the occurrence of abortion due to brucellosis in free-ranging bison in the Jackson herd, suggest that bison in this herd are capable of transmitting brucellosis to other susceptible hosts, and report the first confirmation of brucellosis in this herd. PMID- 8445771 TI - Cilia-associated respiratory bacillus in wild rats in central Iowa. AB - Twenty-eight wild rats were live-trapped in central Iowa (USA) to estimate the prevalence of the cilia-associated respiratory (CAR) bacillus. Both light and electron microscopy were used to look for the Gram-negative, filamentous bacterium among cilia in tracheal and lung tissue sections. The organism was observed in the trachea of 20 rats with chronic respiratory disease and in the trachea of three of eight normal rats. Therefore, the organism appears to be common among wild rats in central Iowa. PMID- 8445772 TI - Isolation of Yersinia enterocolitica (0:5,27 biotype 2) from a common garter snake. AB - Yersinia enterocolitica serotype 0:5,27 biotype 2 was isolated from the intestinal contents of a common garter snake (Thamnophis sirtalis). The isolate possessed virulence associated phenotypes in all tests conducted. It was susceptible to amikacin, ampicillin/sulbactam, aztreonam, cefoperazone, cefotaxime, ceftazidime, ceftriaxone, cefuroxime, ciprofloxacin, gentamicin, imipenem, mezlocillin, norfloxacin, piperacillin, ticarcillin/clavulanic acid, trimethoprim-sulfamethoxazole, tobramycin, chloramphenicol and tetracycline. The isolate harbored the virulence plasmid. PMID- 8445773 TI - An enzyme-linked immunosorbent assay for detecting anthrax antibody in white tailed deer (Odocoileus virginianus): evaluation of anthrax vaccination and sera from free-ranging deer. AB - An enzyme-linked immunosorbent assay for anthrax antibody in white-tailed deer (Odocoileus virginianus) was developed and used to evaluate a vaccination study and compare sera from hunter-killed deer in anthrax endemic and non-endemic areas. Deer subcutaneously vaccinated with anthrax avirulent spore vaccine developed specific antibody to protective antigen (PA) which was significantly higher than the non-vaccinated controls at 30, 60, 90, and 240 days post vaccination. There was no difference between the levels of antibody to PA between deer in anthrax endemic and non-endemic areas. PMID- 8445774 TI - Demodicosis in black bears (Ursus americanus) from Florida. AB - Demodicosis was diagnosed in five black bears (Ursus americanus) from north central Florida. The first bear examined, a 5-yr-old male, had severe alopecia except for the dorsal neck, paws, and ears. The skin was characterized by moderate orthokeratotic hyperkeratosis, and mild to moderate follicular hyperkeratosis. Superficial dermatitis, follicular pustules, and epidermal pustules were present, but rare. Specimens of Demodex sp. were seen most commonly within hair follicles devoid of hair and at the infundibulum of sebaceous glands. Four additional bears from the same area also had some degree of alopecia and skin scrapings were positive for Demodex sp. This mite may be common, although its prevalence is not known. PMID- 8445775 TI - First report of a Demodex sp. in raccoons (Procyon lotor). AB - Demodex spp. mites were seen in skin sections of 5 of 53 raccoons (Procyon lotor) necropsied on Parramore Island, Virginia (USA). In all infections, mites were present in the skin over the lower legs; in one raccoon they also were located in a follicle of a vibrissa. None of the raccoons had Demodex-related gross lesions. Histopathologically, minimal lesions were seen in the affected follicles. This is the first documentation of Demodex spp. in raccoons. PMID- 8445776 TI - Duration of attachment of the chigger, Eutrombicula lipovskyana (Trombiculidae) in mite pockets of Yarrow's spiny lizard, Sceloporus jarrovii (Phrynosomatidae) from Arizona. AB - Duration of attachment was determined for the chigger, Eutrombicula lipovskyana in mite pockets of the phrynosomatid lizard, Sceloporus jarrovii from Arizona. Eutrombicula lipovskyana remained attached in mite pockets for as long as 52 days. Infestations in other body areas were of shorter duration. The mite Geckobiella texana was also found to infest S. jarrovii. PMID- 8445777 TI - Systemic infection with a yeast-like organism in captive banded rock rattlesnakes (Crotalus lepidus klauberi). AB - Three captive banded rock rattlesnakes (Crotalus lepidus klauberi) died at Taronga Zoo, Sydney, Australia, between 1984 and 1987 with similar lesions in each case. Grossly, the liver and kidneys had multiple grey, fleshy nodules replacing much of the parenchyma. Histologically, these lesions were massive accumulations of yeast-like organisms, located mainly within macrophages in capillaries and sinusoids. There was little other inflammatory reaction. Organisms also were seen in the muscle and adventitial coats of the intestine, in the spleen, pancreas, brain, lungs, ovary, and fat body. Apparent budding was observed in fresh smears, and the organisms stained Gram-positive and periodic acid-Schiff positive but failed to grow on routine fungal media. Based on transmission electron microscopy, the organisms were typical yeast cells with thick, apparently single-layered cell walls showing evidence of enteroblastic proliferation. Two of the snakes had concurrent bacterial infections. PMID- 8445778 TI - Asexually proliferous tetrathyridia of Mesocestoides sp. in the hepatic portal system of the prairie rattlesnake (Crotalus viridis viridis). AB - A female prairie rattlesnake (Crotalus viridis viridis) was gastric intubated with 250 tetrathyridia of Mesocestoides sp. The snake was killed 12 wk postinfection; a portion of the liver was examined histologically for evidence of tetrathyridia. Five tetrathyridia were seen in two hepatic portal triad vessels. We propose that a blood-borne metastasis of tetrathyridia in reptiles and rodents may occur. PMID- 8445779 TI - Helminths of the Tsushima leopard cat (Felis bengalensis euptilura). AB - Three Tsushima leopard cats (Felis bengalensis euptilura) in Japan were collected as road kills. Three species of trematodes (Pharyngostomum cordatum, Paragonimus sp. and Dicrocoeliidae gn. sp.), one species of cestode (Spirometra erinacei) and nine species of nematodes (Arthrostoma hunanensis, Uncinaria felidis, Uncinaria sp., Ancylostoma tubaeforme, Molineus springsmithi, Toxocara cati, Capillaria aerophila, Capillaria felis-cati, and Capillaria sp.) were found. Among these helminths, Arthrostoma hunanensis, Uncinaria spp., and Molineus springsmithi have not been reported previously in Japanese domestic cats. PMID- 8445780 TI - Parelaphostrongylus tenuis in Maine moose and the possible influence of faulty Baermann procedures. AB - Efficacy of cleaning Baermann apparati was evaluated to determine if larvae are retained on glassware after evaluating white-tailed deer (Odocoileus virginianus) fecal samples containing Parelaphostrongylus tenuis. Residual P. tenuis larvae were recovered from 7 (11.7%) of 60 Baermann apparati cleaned with soap and tap water. Of 295 moose (Alces alces) fecal samples collected in central and northern Maine, only one contained protostrongylid larvae. Our data do not support the hypothesis that recent increases in Maine's moose population can be attributed to moose becoming a suitable host to P. tenuis. PMID- 8445781 TI - First report of immature Thelazia skrjabini (Nematoda: Thelazioidea) from the eye of a white-tailed deer, Odocoileus virginianus. AB - The eyes from 103 hunter-killed white-tailed deer (Odocoileus virginianus), and 19 mule deer (O. hemionus) killed between 28 November to 14 December 1991 from Wainwright, Alberta were examined for Thelazia spp. One immature male and two immature female Thelazia skrjabini were collected from beneath the third eyelid of one adult female O. virginianus. This is the first report of T. skrjabini in a member of the Cervidae. PMID- 8445782 TI - Cryptosporidiosis in a cotton rat (Sigmodon hispidus). AB - Cryptosporidiosis, previously unreported in cotton rats (Sigmodon hispidus), was observed in one of nine cotton rats from Pryor, Oklahoma (USA). Infection was confined to the large intestine. Microscopically, numerous cryptosporidians measuring 2 to 3 microns in diameter were intimately associated with the luminal surface of colonic and rectal mucosae. The affected lamina propria of the large intestine was diffusely infiltrated by eosinophils, lymphocytes and macrophages. Ultrastructurally, numerous trophozoites and a single schizont were observed. Microvilli were displaced by the presence of cryptosporidians at the attachment site. PMID- 8445783 TI - Severe moniliformiasis (Acanthocephala: Moniliformidae) in a gray squirrel, Sciurus carolinensis, from Arkansas, USA. AB - Three hundred and seventy-five acanthocephalans, Moniliformis clarki, were removed from the small and large intestines of a gray squirrel from Arkansas County, Arkansas (USA). This is the first report of M. clarki from Arkansas. Enteric lesions, including distension, perforating ulcers, enteritis, crypt hypertrophy, goblet cell hyperplasia, and occlusions of the intestinal tract were observed, indicating the pathogenic potential of this parasite. PMID- 8445784 TI - Mosaic 35,X/36,XY karyotype and intersex in a red panda (Ailurus fulgens fulgens). AB - A zoo-bred Himalayan red panda (Ailurus fulgens fulgens) was diagnosed as a presumptive intersex on clinical examination at 4-mo-of-age. The phenotype was predominantly female but showed a large anogenital distance and bilateral ischial swellings. Based on cytogenetic evaluation, the karyotype was mos35,X/36,XY, with 50% of each cell type. A grossly normal uterus and oviducts were seen with laparoscopic examination, while the gonads were smooth-surfaced, with a ramifying vascular pattern. On histopathologic examination the bulk of the gonads consisted of clumps of poorly differentiated cells, with just a thin rim of ovarian tissue under the region covered by the fimbriae of the oviduct. PMID- 8445785 TI - Immobilization of common genets, Genetta genetta, with a combination of ketamine and xylazine. AB - A total of 15 immobilizations were performed on 12 common genets (Genetta genetta) with a combination of ketamine hydrochloride (KE) and xylazine hydrochloride (XY). Ten immobilizations were successful using a single mean administration of 5.7 mg/kg (SD = 1.7) KE and 9.8 mg/kg (SD = 2.9) XY; five immobilizations required supplemental doses that averaged 3.4 mg/kg KE and 1.9 mg/kg XY. Initial doses of 7 mg/kg KE and 10 mg/kg XY are recommended to successfully immobilize genets. Mean induction time and arousal time were 8 min (SD = 4, n = 10) and 113 min (SD = 57, n = 9), respectively. A combination of KE and XY appears to be an effective and safe immobilizing agent for common genets. PMID- 8445786 TI - Re-evaluation of the C120 Magnum and Bionic traps to humanely kill mink. PMID- 8445787 TI - Immune function in free-ranging harbor seal (Phoca vitulina) mothers and their pups during lactation. AB - Immune function in harbor seal mothers and their pups during lactation was studied on Sable Island, Nova Scotia, Canada, during the springs of 1989 and 1990. Methods included total white blood cell and differential counts, a Protein A enzyme linked immunosorbent assay (ELISA) for total immunoglobulin G (IgG) quantification, and functionality testing of lymphocytes in vitro using the T cell mitogen concanavalin A (ConA). Lymphocyte functionality and total IgG levels were reduced in the mothers at the end of lactation, suggesting a reduction in immune function, possibly as a result of the stress of fasting, or hormonal changes associated with lactation and estrus. By contrast, lymphocyte functionality and total IgG levels in pups were low at birth and higher at the end of lactation. Pups at birth and females late in lactation may therefore be more susceptible to infection by viral and bacterial agents. This study represents the first broad examination of immune function in a free-ranging pinniped population. PMID- 8445788 TI - Pasteurella haemolytica cytotoxin-dependent killing of neutrophils from bighorn and domestic sheep. AB - Peripheral blood neutrophils from Rocky Mountain bighorn sheep (Ovis canadensis canadensis) and domestic sheep were exposed to culture supernatants from Pasteurella haemolytica isolates recovered from these two sheep species. Six culture supernatants from bighorn sheep isolates and two from domestic sheep isolates were tested for cytotoxicity as determined by the release of lactate dehydrogenase. Two of the bacterial culture supernatants from bighorn sheep were not cytotoxic, while the other four bighorn sheep culture supernatants were effective cytotoxins on both bighorn (> 95% cell death at 150 micrograms of cytotoxin) and domestic sheep neutrophils (55 to 95% cell death at 150 micrograms of cytotoxin). Two culture supernatants of P. haemolytica from domestic sheep were effective cytotoxins on both bighorn (> 95% cell death at 150 micrograms of cytotoxin) and domestic sheep (70 to 75% cell death at 150 micrograms of cytotoxin) neutrophils. Potency of cytotoxins derived from P. haemolytica isolates from bighorn sheep was three to seven-fold higher when tested with bighorn sheep neutrophils as compared to domestic sheep neutrophils. Cytotoxins derived from P. haemolytica isolates from domestic sheep were five to six-fold more potent when tested with bighorn sheep neutrophils than when domestic sheep cells were used. PMID- 8445789 TI - Seroprevalence of infectious disease agents in free-ranging Florida panthers (Felis concolor coryi). AB - Serum samples obtained from 38 free-ranging Florida panthers (Felis concolor coryi) in southern Florida, March 1978 through February 1991, were tested for antibodies against eight bacterial, parasitic, and viral disease agents. Sera were positive for antibodies against feline panleukopenia virus (FPV) (78%), feline calicivirus (56%), feline immunodeficiency virus/puma lentivirus (37%), feline enteric coronavirus/feline infectious peritonitis virus (19%), and Toxoplasma gondii (9%). All samples were seronegative for Brucella spp., feline rhinotracheitis virus, and pseudorabies virus. In addition, all the animals tested were negative for feline leukemia virus p27 antigen as determined by enzyme-linked immunosorbent assay. Feline panleukopenia virus was considered to be a potentially significant disease agent; FPV antibodies occurred in the highest prevalences in older age classes (P = 0.027) and in panthers living in the dense mixed hardwood swamps in the western portion of their range compared to the open cypress and sawgrass prairies to the east (P = 0.096). Because < 50 animals remain in this relict population and the probable resultant depression of genetic diversity and lowered disease resistance, FPV or other disease agents could contribute to the extinction of this endangered subspecies. PMID- 8445790 TI - Lizard erythrocytic virus in east African chameleons. AB - Giemsa-stained peripheral blood films from 9 of 50 flap-necked chameleons, Chamaeleo dilepis, and 1 of 18 Fischer's chameleons, Bradypodion fischeri, collected in Tanzania had intraerythrocytic inclusions. In C. dilepis, acidophilic inclusions were associated with the albuminoid vacuoles reported in typical pirhemocytonosis of saurians. Under transmission electron microscopy, the acidophilic inclusions were aggregations of partially or completely formed viral particles consistent with those of the family Iridoviridae. Enveloped viral particles were 140 to 180 nm in diameter, with a mean of 159 nm (SD, 12). Albuminoid vacuoles were not seen in the B. fischeri infection, in which erythrocytes contained multiple acidophilic inclusions of variable shape. Viral particles in B. fischeri were 156.3 to 200.0 nm in diameter; the mean was 180 nm (SD, 18). This represents the first confirmation of the viral identity of pirhemocyton in a lizard. We recommend that the epithet pirhemocyton no longer be used as a generic name under the International Code of Zoological Nomenclature, and that future reports of the etiologic agent refer to it as Lizard Erythrocytic Virus. PMID- 8445791 TI - Prevalence of the Lyme disease spirochete, Borrelia burgdorferi, in deer ticks (Ixodes dammini) collected from white-tailed deer (Odocoileus virginianus) in Saint Croix State Park, Minnesota. AB - During a special two-day hunt (11, 12 November 1989) in Saint Croix State Park, Minnesota (USA), one side of the neck for each of 146 white-tailed deer (Odocoileus virginianus) was examined for ticks. Of the 5,442 ticks collected, 90% (4,893) were the winter tick, Dermacentor albipictus, and 10% (549) were the deer tick, Ixodes dammini, the primary vector of the causative agent of Lyme disease, Borrelia burgdorferi. Adult males had the greatest frequency of infestation of either D. albipictus (100%) or I. dammini (88%) and had on average more ticks, compared to other deer. Based on an examination of midgut material from 435 I. dammini by polyclonal antibody analysis, spirochetes were observed in 22% of the ticks. Species-specific monoclonal antibody analysis of the spirochetes confirmed that the bacteria were B. burgdorferi. PMID- 8445792 TI - Morphology, prevalence, and distribution of Sarcocystis spp. in white-tailed deer (Odocoileus virginianus) from Florida. AB - Three morphologically distinct types of sarcocysts (I, II, and III) were identified by light microscopy in tongues from 403 white-tailed deer (Odocoileus virginianus) collected in Florida (USA) over a 7-yr-period. Based on electron microscopy of representative examples of these sarcocysts, there were four distinctive wall structures. We concluded that one of these (Type I) was representative of Sarcocystis odocoileocanis and another (Type III) was representative of an unnamed species previously described from white-tailed deer in Montana. Type II could be divided further into two forms (IIA and IIB) that may represent two underscribed species or developmental stages of the same species. Sarcocystis odoi, another previously recognized sarcosporidian from white-tailed deer, was not found. Sarcocysts of Types I and II were distributed nonrandomly in tongue muscle, being more common in the basal portion, whereas Type III was distributed randomly throughout the tongue. Single infections (one of the three types) accounted for 63% of the infected deer, while double infections occurred in 28% and triple infections in 4%. Types I and II were found in deer throughout the state, but Type III occurred only in deer from southern Florida. In 1988 and 89, the statewide prevalences for Types I, II, and III were 57, 20, and 6%, respectively. Prevalences of Type I ranged from 94% in the panhandle region (northern Florida) to 34% in the southern part of the state. Prevalences of all three types increased with age. PMID- 8445793 TI - Observations on waterfowl carcasses during a botulism epizootic. AB - Several features related to waterfowl carcasses were studied at Eyebrow Lake, Saskatchewan, Canada, during a botulism epizootic in the summer of 1989. Dummy carcasses, constructed by stretching duck skins over wooden forms, were used to assess the reaction of waterbirds to carcasses. There was no significant difference in the number of American coots, ducks, grebes, or total birds present when dummy carcasses were or were not present. Only one of 42 freshly-dead bird carcasses marked and observed twice each day was removed by a scavenger prior to the development of large maggots. Maggots developed in all carcasses and were visible externally a mean of 3.9 days after placement of the carcasses. The effectiveness of carcass collection and disposal operations was tested by marking carcasses on the day prior to two scheduled clean-ups. Only 32% of marked carcasses were recovered. Large carcasses and carcasses on or near islands were recovered at a higher frequency than were small carcasses and carcasses not near islands, respectively. PMID- 8445794 TI - Efficacy of in-feed formulation ivermectin against Psoroptes sp. in bighorn sheep. AB - Four Rocky Mountain bighorn sheep (Ovis canadensis canadensis) were experimentally inoculated with Psoroptes sp. of bighorn sheep origin by placing approximately 50 mites into each ear. Two sheep developed reproducing mite colonies and lesions consisting of alopecia, and exudative dermatitis with scabs on ears, face and neck. Three months after inoculation, all four sheep were treated with an in-feed formulation of ivermectin at a dosage of 1 mg/kg of body weight in a pelleted ration daily for seven consecutive days. Mites could not be detected on any of the sheep 1, 2, or 3 mo after treatment, and lesions on the affected sheep resolved within 6 to 8 wk after treatment. Thus, under these conditions, ivermectin was completely effective in eliminating the mites; it also was palatable and nontoxic. Use of ivermectin in pelleted feed for field treatment of psoroptic mange is encouraged. PMID- 8445795 TI - Sex- and age-specific lungworm infection in Rocky Mountain bighorn sheep during winter. AB - Sex- and age-specific fecal lungworm (Protostrongylus spp.) larvae concentrations in Rocky Mountain bighorn sheep (Ovis canadensis canadensis) from the Cinnabar Winter Range in southwestern Montana were determined. All 228 fecal samples collected from bighorn sheep of known sex and age class from November to April, 1984 to 1987 contained first-stage lungworm larvae. Fecal lungworm concentrations of ewes and rams declined significantly from late fall through early spring, whereas number of lungworms in lamb feces increased as winter progressed. PMID- 8445796 TI - Composition of prepartum mammary secretions of two bowhead whales (Balaena mysticetus L.). AB - Mammary secretions from two bowhead whale (Balaena mysticetus L.) females carrying near-term fetuses were analyzed for dry matter, ash, protein, fat, carbohydrate and energy content. Protein values ranged from 75.9% to 97.3% of dry matter. Fat ranged from 0.6% to 9.1% of dry matter. A protein corresponding to beta-lactoglobulin on gel filtration chromatography was the predominant whey protein. Neutralizing antibodies to nine caliciviruses were detected in one sample. Composition of these two samples differs from previous reports for cetacean milk, perhaps due to the stage of lactation. PMID- 8445797 TI - Vitamin E in cranes: reference ranges and nutrient interactions. AB - Fat soluble vitamins E and A (quantified as alpha-tocopherol and all-trans retinol, respectively) were measured in plasma samples from 274 captive cranes from four institutions and five free-ranging birds. Ages ranged from 4 mo to 80 yr, and all 15 crane species were represented. Captive cranes had a mean +/- standard error (SE) of 6.57 +/- 0.82 micrograms/ml alpha-tocopherol; migrating greater sandhill cranes (Grus canadenis tabida) had a plasma concentration of 3.71 +/- 0.22 micrograms/ml. Sex and age differences were not significant, but crane species that evolved in temperate habitats had higher circulating levels of alpha-tocopherol than tropical or subtropical species. Mean +/- SE retinol values were 0.69 +/- 0.05 micrograms/ml in captive cranes, and 0.66 +/- 0.08 micrograms/ml in free-ranging cranes; values did not differ significantly by sex, age, or species. Dietary vitamin E concentrations were significantly correlated with plasma alpha-tocopherol levels in a logarithmic relationship. Dietary selenium at 0.5 mg/kg was associated with decreased circulating alpha-tocopherol concentrations. PMID- 8445798 TI - Improving preschool immunization levels proving more complex than simply providing vaccines. PMID- 8445799 TI - New association looks at environmental hazards; groups worldwide ponder challenges involved. PMID- 8445800 TI - Neurophysiology, philosophy on collision course? PMID- 8445801 TI - From the Centers for Disease Control and Prevention. Effectiveness of rollover protective structures for preventing injuries, agricultural tractors. PMID- 8445802 TI - From the Centers for Disease Control and Prevention. Pertussis surveillance- United States, 1989-1991. PMID- 8445803 TI - From the Centers for Disease Control and Prevention. Tetanus fatality--Ohio, 1991. PMID- 8445804 TI - Second-opinion trial in patients recommended for coronary angiography. PMID- 8445806 TI - Second-opinion trial in patients recommended for coronary angiography. PMID- 8445805 TI - Second-opinion trial in patients recommended for coronary angiography. PMID- 8445807 TI - Second-opinion trial in patients recommended for coronary angiography. PMID- 8445808 TI - Second-opinion trial in patients recommended for coronary angiography. PMID- 8445809 TI - Screening blood donors by computer interview. PMID- 8445810 TI - Metered-dose inhalers: the specified number of sprays. PMID- 8445811 TI - JFK revisited. PMID- 8445812 TI - Aerodynamic handlebars. PMID- 8445813 TI - Terfenadine-ketoconazole interaction. Pharmacokinetic and electrocardiographic consequences. AB - OBJECTIVE: To examine prospectively the effects of ketoconazole on the pharmacokinetics and electrocardiographic repolarization pharmacodynamics (corrected QT intervals) of terfenadine in men and women. DESIGN: Prospective cohort study with each subject serving as his or her own control. SETTING: Outpatient cardiology clinic and inpatient telemetry unit for monitoring period. PARTICIPANTS: Six healthy volunteers (four men and two women, aged 24 to 35 years) not taking any prescription or over-the-counter medications. INTERVENTION: After achieving a steady state while taking terfenadine (60 mg every 12 hours for 7 days), daily concomitant oral ketoconazole (200 mg every 12 hours) was added to the subjects' regimen. Pharmacokinetic profiles were obtained while subjects were taking terfenadine alone and after the addition of ketoconazole. Electrocardiograms were obtained at baseline, after 1 week of taking terfenadine alone, and at the time of the second pharmacokinetic profile after the addition of ketoconazole to the regimen. MAIN OUTCOME MEASURES: Terfenadine and its acid metabolite serum concentrations and corrected QT intervals. RESULTS: All subjects had detectable levels of unmetabolized terfenadine after the addition of ketoconazole, which was associated with QT prolongation. Only two of the six subjects could complete the entire course of ketoconazole coadministration. Four subjects received a shortened duration of ketoconazole therapy because of significant electrocardiographic repolarization abnormalities. There was a significant change in the area under the curve of the acid metabolite of terfenadine after the addition of ketoconazole administration. CONCLUSIONS: Ketoconazole alters the metabolism of terfenadine in normal men and women and results in the accumulation of unmetabolized parent drug, which is associated with significant prolongation of the corrected QT interval. This drug combination should be avoided. PMID- 8445814 TI - The impact on infant birth weight and gestational age of cotinine-validated smoking reduction during pregnancy. AB - OBJECTIVE: To evaluate the impact of cotinine-confirmed smoking reduction during pregnancy on infant birth weight and gestational age at birth. DESIGN: Group analyses from a prospective, randomized smoking-cessation intervention trial using cotinine levels to assess smoking cessation and reduction. SETTING: Four maternity clinics of Jefferson County Health Department in Birmingham, Ala. PATIENTS: A total of 803 pregnant smokers and 474 never smokers with a fetal gestational age of 32 weeks or less at the first prenatal visit to a clinic. MAIN OUTCOME MEASURES: Infant birth weight and gestational age at birth. RESULTS: Infants who were born to women who quit smoking (quitters) had the highest mean birth weight (3371 +/- 581 g), followed by infants who were born to women who did not change smoking behavior (no changers) (3043 +/- 587 g). The mean infant birth weight of infants born to the quitters, adjusted by mother's age, race, height, weight at baseline, and gestational age at delivery was 241 g heavier than that among the no changers (P = .0008) and 167 g heavier than the reducers (P = .04). The adjusted mean infant birth weight of infants born to the reducers was 92 g heavier than that among the no changers (P = .08). White reducers with baseline cotinine levels greater than 100 ng/mL had infants who were 241 g heavier than did white no changers. A 220-g difference was also seen in black reducers with a baseline cotinine level of 100 ng/mL or less. Although smoking cessation increased infant gestational age at delivery by 1 week, smoking reduction had little effect. CONCLUSION: Cotinine-validated smoking reduction rates were positively associated with an increase in infant birth weight. While smoking cessation must continue to be the primary objective for pregnant smokers, specific intervention methods should also be directed toward smoking reduction for women who cannot quit. PMID- 8445815 TI - Temporal and geographic trends in the autopsy frequency of blunt and penetrating trauma deaths in the United States. AB - OBJECTIVE: To examine national trends in the percentage of blunt and penetrating trauma deaths autopsied. DESIGN, SETTING, AND PARTICIPANTS: For each year from 1980 through 1989, we used national mortality data files to determine the autopsy frequency (percentage of deaths autopsied) of all deaths in the United States. We analyzed variation in the autopsy frequency of blunt and penetrating trauma deaths by cause of injury and place of occurrence of death. RESULTS: The autopsy frequency of blunt and penetrating trauma deaths in the United States increased by 14.3% during the 1980s to 58.9% in 1989 (62,004 of 105,309 deaths autopsied), while the autopsy frequency of all deaths decreased by 23.6% during the same period to 11.5% in 1989 (248,272 of 2,153,859 deaths autopsied). Among trauma deaths, homicides remained far more likely to be autopsied than nonhomicides (deaths due to unintentional injuries, suicides, and injuries of undetermined intentionality). The autopsy frequency of homicidal trauma deaths in 1989 was 90.0% or higher in 44 states and ranged from 79.6% in Mississippi to 100.0% in six states. The autopsy frequency of nonhomicidal trauma deaths in 1989 was 90.0% or higher in two states and ranged from 10.3% in Oklahoma to 94.5% in Hawaii. Nationwide, we found significant differences in the autopsy frequency of trauma deaths in 1989 between metropolitan and nonmetropolitan counties, both for homicides (97.7% vs 89.3%; P < .001) and nonhomicides (58.2% vs 29.9%; P < .001). CONCLUSIONS: The percentage of blunt and penetrating trauma deaths autopsied has increased recently in the United States, but extensive geographic variation in autopsy frequency suggests that the benefits of autopsy findings for trauma care quality improvement and public health surveillance of injuries are distributed unevenly throughout the nation. PMID- 8445816 TI - Mechanism of the cardiotoxic actions of terfenadine. AB - OBJECTIVES AND METHODS: To gain insight into possible mechanisms of and predisposing factors for torsades de pointes during terfenadine therapy, spontaneous reports in the US Food and Drug Administration's Spontaneous Reporting System database were examined. Based on the characteristics of the cases, in vitro cardiac electrophysiologic studies were conducted to test the hypothesis that terfenadine, and not its major metabolite, has actions similar to those of quinidine and is responsible for this form of cardiac toxicity. DESIGN: Spontaneous reports from the general medical community. RESULTS: As of April 1, 1992, 25 cases of torsades de pointes had been reported to the Food and Drug Administration's Spontaneous Reporting System. Predisposing factors in these cases indicated that the parent drug, but not its metabolite, may have actions similar those of quinidine that are responsible for inducing arrhythmia. In vitro studies found that terfenadine is equipotent to quinidine as a blocker of the delayed rectifier potassium current in isolated feline myocytes. The metabolite, terfenadine carboxylate, did not inhibit this potassium current even at concentrations 30 times higher than the concentration of terfenadine producing a half-maximal effect. CONCLUSIONS: Since blockade of the potassium channel did not occur with the major metabolite of terfenadine, episodes of torsades de pointes are most likely the result of a quinidinelike action of the parent drug and of factors that impair the normally rapid metabolism of terfenadine. Dosage restriction and awareness of the clinical conditions and drug interactions capable of inhibiting the metabolism of terfenadine are essential for prevention of this serious reaction. PMID- 8445817 TI - Ethnicity as a risk factor for inadequate emergency department analgesia. AB - OBJECTIVE: To determine whether Hispanic patients with isolated long-bone fractures are less likely to receive emergency department (ED) analgesics than similar non-Hispanic white patients. DESIGN: Retrospective cohort study. SETTING: The UCLA Emergency Medicine Center, a level I trauma center. PARTICIPANTS: All Hispanic and non-Hispanic white ED patients aged 15 to 55 years, seen between January 1, 1990, and December 31, 1991, with isolated long-bone fractures, identified by ICD-9 codes 812, 813, 821, and 823, were eligible for inclusion. Exclusion criteria included injury more than 6 hours prior to presentation, "possible" or chip fractures only, altered mentation, or ethanol intoxication. MAIN OUTCOME MEASURES: Emergency department administration of analgesic or no analgesic. RESULTS: The study group consisted of 139 patients meeting inclusion criteria, of whom 31 were Hispanic and 108 non-Hispanic white. Non-Hispanic whites were significantly more likely to speak English, be insured, and suffer nonoccupational injuries. Hispanics were twice as likely as non-Hispanic whites to receive no ED pain medication (crude relative risk [RR], 2.12; 95% confidence interval [CI], 1.35 to 3.32; P = .003). The RR for ethnicity was similar and significant (P < .05) after controlling by stratification for covariates related to patient, injury, or physician characteristics. After controlling for several covariates simultaneously through multiple logistic regression, ethnicity remained the strongest predictor of ED analgesic administration (odds ratio [OR], 7.46; 95% CI, 2.22 to 25.04; P < .01). CONCLUSIONS: Hispanics with isolated long bone fractures are twice as likely as non-Hispanic whites to receive no pain medication in the UCLA Emergency Medicine Center. No covariate measured in this study could account for this effect. An ethnic basis for variability in analgesic practice needs to be further characterized. PMID- 8445818 TI - JFK's assassination. Conspiracy, forensic science, and common sense. PMID- 8445819 TI - Additional data on the shooting of President Kennedy. PMID- 8445820 TI - It's time to wake up to the importance of sleep disorders. PMID- 8445821 TI - Understanding consequences of concurrent therapies. PMID- 8445822 TI - JFK--an allonge. PMID- 8445823 TI - [Electromyogram measuring method for low back load evaluation of handling weight and forward bending posture]. AB - In order to establish a measuring method of electromyogram (EMG) to evaluate the low back load by handling weight and forward bending angle. EMG at Th5-6, Th8-9, Th11-12, L1-2 and L3-4 were measured in ten male subjects. The handling weight was changed at 0, 10, 20 and 30 kg, and the forward bending angle was changed at 0, 30, 60 and 90 degree. The following results were obtained: 1) EMG increased according to the handling weight at all forward bending angles. The increasing rate of EMG at Th5-6 was larger than that at L1-2 or L3-4. Thus, EMG at higher position such as Th5-6 was found to be appropriate to evaluate handling weight load. 2) The effect of forward bending angle was different by handling weight. EMG at L1-2 and L3-4 increased according to forward bending angle when the handling weight was 0 kg or 10 kg and when the forward bending angle was not greater than 60 degree. However, when the handling weight was 20 kg or 30 kg, EMG and forward bending angle did not show a simple proportional relationship. Thus, EMG at L1-2 or L3-4 could be used to evaluate posture load when the handling weight was light and the bending angle was not so large. However, it was difficult to use EMG to evaluate posture load when the forward bending angle was large or the handling weight was heavy. PMID- 8445824 TI - Sex difference in free erythrocyte protoporphyrin (FEP) level. IV. Sex difference in FEP level in rabbits exposed to lead. AB - An experimental study on Japanese White (JW) rabbits was conducted to clarify the sex difference in FEP level. Male and female rabbits (n = 14 of each sex) were used. The animals of the same sex were divided into 3 groups; i.e., control group (5% glucose solution only, n = 4), low lead dose group (Pb 0.4 mg/kg.BW, n = 5) and high lead dose group (Pb 2 mg/kg.BW, n = 5). Lead was injected intravenously twice a week for 5 wk. The following parameters were determined once a week for 5 wk: blood lead (Pb-B), FEP, Ht, Hb, erythrocyte ALA-D activity, erythrocyte pyrimidine 5'-nucleotidase (P5N), urinary coproporphyrin (CP-U), urinary delta aminolevulinic acid (ALA-U), iron in serum (Fe-S), and serum GOT and GTP. Average levels of FEP in female rabbits were higher than those in males between the 1st and 3rd week after the lead injection in the low lead dose groups, and in the final week in the high lead dose groups. In the periods without lead injection, the average levels of FEP in the female groups were not significantly higher than the corresponding levels in the male groups in every week except in the first week in the control. However, the mean of FEP levels in all female rabbits without Pb treatment was higher than that in male rabbits (t-test). By the analysis of variance for the gains of FEP from the initial value, only the low lead dose group showed a significant sex difference (female > male); that is, the female group tended to increase when compared with the male group. Furthermore, the week when FEP began to increase in the female groups was earlier than that in the male groups in the low lead dose group. In the high lead dose group, both sexes reacted to the lead exposure from the same early week. As for the parameters of anemia, the average levels of Ht and Hb tended to be lower in females than in males, but Fe-S levels were not affected by lead in both sexes and no consistent sex difference could be observed. By lead exposure, ALA-D and P5N were inhibited, and ALA-U was increased, but these parameters showed no evident sex difference. The average levels of CP-U tended to be higher in females than in males in the administration of low lead dose and to be inversely higher in males than in females in the administration of high lead dose.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8445825 TI - [Relationship between lymphocyte subsets of the peripheral blood and noise induced hearing loss]. AB - Biochemical examination and two-color flow cytometric analysis of lymphocyte subsets of the peripheral blood were carried out in 107 healthy males working in high noise environments. The level of hearing disorder was compared with these results. By audiometry at six frequency levels, 51 of the 107 healthy males showed hearing loss. Their mean value of hearing ability was 30 dB and/or above. Among the peripheral lymphocyte subsets, helper T cells of CD4+CD45R- were significantly increased and the CD4/CD8 ratio tended to be elevated. CD20 that indicate B cells were reduced. These results suggested a relationship between susceptibility to acoustic trauma and cell-mediated immunity. PMID- 8445826 TI - Significance of two obesity indices, Broca-Katsura and Quetelet, compared with Abdel-Malek index. PMID- 8445827 TI - [Metabolism of organotin compounds in rats after a single oral administration of diphenyltin or dibutyltin compounds]. PMID- 8445828 TI - [A case report with special reference to correlation between increased hematocrit and angina on effort]. PMID- 8445829 TI - [Mental health, work environment, and health practices among middle-aged male workers]. AB - A study was made on the cross-sectional relationship of the psychosocial work environment and personal health practices to mental health level among 15,639 male subjects aged 30-59 engaged in various kinds of occupations and firms. Mental health level was dichotomized by self-reported mental disorders. The psychosocial factors of work environment were conceptually constructed from the aspects of working conditions and occupational stress. Working conditions were assessed by work overload, work shifts and role in the organization. Occupational stress was measured by psychological work load and job characteristics (job demands and decision latitude). Various factors associated with positive health behavior--an index based on six parameters such as supper time, physical exercise, smoking, alcohol consumption, sleep, and weight--were examined. The prevalence of self-reported mental disorders was 17.5 per 1,000 population. Multiple logistic analysis showed that both psychological work load and health practice index have a significant independent effect on mental health levels after controlling for age and marital status. Limitations of the present study indicate a need for future longitudinal studies. PMID- 8445830 TI - Transplantation in peritoneal dialysis and hemodialysis. PMID- 8445831 TI - Residual renal function and recovery of renal function in patients treated by CAPD. PMID- 8445832 TI - Anemia and erythropoietin in hemodialysis and continuous ambulatory peritoneal dialysis. PMID- 8445833 TI - Non-medical factors that impact on ESRD modality selection. PMID- 8445834 TI - Comparative morbidity among hemodialysis and continuous ambulatory peritoneal dialysis patients. PMID- 8445835 TI - Quality of life in patients undergoing renal replacement therapy. AB - Rehabilitation can be achieved by renal replacement therapy. The evidence to date would indicate that most successfully transplanted patients achieve rehabilitation both on objective and subjective criteria and in a cost effective manner; however, unsuccessful transplantation has a poor quality of life outcome. Some home dialysis patients achieve the same goals; these two groups comprise predominantly younger patients free of systemic disease. For the high risk group of patients which are predominantly managed by ICHD and CAPD, the objective evidence of rehabilitation is lacking; however, perceived quality of life on subjective measures shows results comparable to a normal population. Comparisons between ICHD and CAPD populations are difficult with different modality related stressors imparting stress to the patients. CAPD has marginal advantage over ICHD. Overall, from these studies, it seems that while successful transplantation imparts the best quality of life on both objective and subjective parameters, the differentiation between ICHD and CAPD is that much more difficult; what evidence there is would suggest that CAPD patients are marginally to moderately better rehabilitated, certainly on subjective parameters. The results in the studies suggest that patients with end-stage renal disease are able to adapt to very adverse life circumstances, nevertheless expressing considerable satisfaction with their lives. PMID- 8445836 TI - Urea kinetic and middle molecule approaches to assessing the adequacy of hemodialysis and CAPD. AB - The historical bases and implications of the urea kinetic and middle molecule approaches to assessing the adequacy of hemodialysis and continuous ambulatory peritoneal dialysis (CAPD) are reviewed in this paper. A critical reappraisal of the findings of the National Cooperative Dialysis Study (NCDS) demonstrates the importance of small solute removal on clinical outcomes of morbidity and mortality in the hemodialysis setting. The applicability of these results to CAPD is examined in the light of differences in transport characteristics of hemodialysis membranes and the peritoneal membrane. It is shown that small solute removal is important even in assessing CAPD adequacy and that past comparisons of hemodialysis and peritoneal membrane transport may have been flawed. The extrapolation of NCDS results to CAPD on the basis of the peak concentration hypothesis is presented along with a review of several longitudinal, cross sectional, and multicenter studies of CAPD morbidity and mortality. PMID- 8445837 TI - Nutrition and adequacy of dialysis. How do hemodialysis and CAPD compare? PMID- 8445838 TI - Morbidity and mortality of CAPD and hemodialysis. AB - We have reappraised studies on morbidity and mortality in continuous ambulatory peritoneal dialysis (CAPD), comparing it with hemodialysis (HD), the standard treatment for end-stage renal disease (ESRD). More hospitalization is required for CAPD, the difference being related to peritonitis, to the more frequent presence of some risk factors (such as diabetes and atherosclerosis) in the patients selected for CAPD, and to the lack of experience in the early years of CAPD practice. CAPD patients have less acute morbidity during treatment that not always requires hospitalization: hypotension, hypertension, arrhythmias, and myocardial ischemia. Cardiac performance is also better in CAPD patients, who develop less myocardial hypertrophy than HD patients. Hospitalization due to infectious disease not referable to technique, beta 2-microglobulin related morbidity, signs of uremic neuropathy, osteodystrophy, and malnutrition are similar in both groups. Method survival is better for HD, the difference being completely accounted for by peritonitis. Patient survival adjusted for pre treatment differences is similar in CAPD and HD, and this is not an artifact of more drop-outs on CAPD. A high incidence of peritonitis is accompanied by an increased risk of death. Older patients have a lesser risk of death on CAPD than on HD. Diabetics have a worse survival than non-diabetics, with no difference between the two methods. Although patient survivals on CAPD and HD are the same, differences in the mode of blood purification have an interesting impact on particular aspects of morbidity. PMID- 8445839 TI - Dialysis therapy in the elderly patient. AB - It is clear that an increasing number of elderly patients will require ESRD care as the decade proceeds. Currently available data suggest that outcomes on HD and CPD are similar in this patient group, although the data in elderly diabetics are not all in. A number of questions remain to be answered, however: (1) Can severity indices be developed so that patients can be properly matched for co morbid conditions? This is essential if firm conclusions about the outcome of one modality compared to another can be drawn. (2) Is survival of elderly diabetics worse on CPD compared to HD? If so, is this because of differences in patient selection or co-morbidity or in the effects of the modality? (3) Can a simple, easy to use modality selection algorithm be developed for the elderly ESRD patient? (4) What factors add to the risk of morbidity and mortality in elderly ESRD patients, and how they can be modified? (5) What is the incidence of malnutrition in elderly ESRD patients? How does it relate to morbidity and mortality? Does it differ from those on HD compared to CPD? (6) Are there elderly patients who should not be started on dialysis? How can they be identified? PMID- 8445840 TI - Dialysis considerations for diabetic patients. PMID- 8445841 TI - Continuous peritoneal dialysis for children: a decade of worldwide growth and development. AB - This review surveys the dramatic worldwide expansion of the use of continuous peritoneal dialysis as maintenance renal replacement therapy for children with end-stage renal disease that has occurred during the past decade. Before 1982, fewer than 100 pediatric patients had been treated with continuous ambulatory peritoneal dialysis (CAPD), and continuous cycler peritoneal dialysis (CCPD) for children was virtually unknown. By the end of 1989 CAPD/CCPD was accounting for 50% of pediatric dialysis patients (less than 15 years old) in the United States, 65% in Canada, and 75% in Australia/New Zealand. Growth of CAPD/CCPD for children in Europe overall has been less spectacular, but there is wide variability from country to country, with CAPD/CCPD concentrated in eight member countries of the European Dialysis and Transplant Association. Several of these countries (notably the United Kingdom, Israel, the Netherlands and the former Federal Republic of Germany) were treating 46% to 70% of pediatric patients with CAPD/CCPD by the end of 1987. Other European countries such as France and Spain showed little growth of CAPD/CCPD over the decade (10% to 20% of patients treated with CAPD/CCPD). In Japan, CAPD for children has just begun, but because Japanese children are likely to spend longer periods on dialysis awaiting transplantation, information on long term use of CAPD/CCPD in children may be forthcoming from Japan in the future. No effort is made to compare CAPD/CCPD to hemodialysis as a maintenance therapy for children. The advantages of CAPD/CCPD for the young patient, especially the infant and very young child are noted, and from the past decade of dramatic worldwide growth of CAPD/CCPD in pediatric patients it is inferred that the majority of children, (from 50% to 75%) can be successfully treated with these modalities, at least for the short-term (that is, several years), while awaiting transplantation. PMID- 8445842 TI - Complications of peritoneal dialysis related to increased intraabdominal pressure. PMID- 8445844 TI - Options in dialysis therapy: significance of cardiovascular findings. AB - Most patients receiving renal replacement therapy have cardiovascular disease. The most frequent conditions are left ventricular hypertrophy and coronary artery disease. Hemodialysis is associated with a characteristic spectrum of acute complications (such as hypotension, sudden death) that can be explained by typical dialysis-induced effects on the heart. With continuous ambulatory peritoneal dialysis (CAPD) some of those cardiovascular complications are ameliorated due to slow ultra-filtration and absence of an arteriovenous fistula. It is concluded that CAPD might be the preferable option in patients with cardiovascular disease when hemodialysis can only be performed in a standardized and often aggressive manner. However, achievement of medically-defined goals appears to be more important than technique in dialysis therapy. PMID- 8445843 TI - Access problems plague both peritoneal dialysis and hemodialysis. AB - Both chronic peritoneal dialysis and center hemodialysis require a transcutaneous access. Costs of maintaining access to the bloodstream and the costs of maintaining access to the peritoneal cavity are substantial for both therapies. Complication rates for blood access clotting and exit site infection may be similar. Exit site infections can often be treated on an outpatient basis. Clotted blood access devices frequently need surgical revision. Peritonitis can in some instances be related to access (excluding internal sources for peritonitis), but with newer devices these rates can be as low as 0.5 episodes per patient year or lower. Thus, the sum of exit site infection rates and peritonitis rates may give totals approaching one episode per patient year. If clotted access incident rates are near half of this, as the recently quoted study suggests, then overall access complications may be more common in peritoneal dialysis. However, the outpatient treatment of most episodes of peritonitis and the outpatient treatment of many if not most episodes of exit site infection implies a lower level of severity than a clotted access device requiring hospitalization and surgical revision. Also of note, bacteremia is a rare complication of exit site infection and peritonitis. In contract, bacteremia and sepsis occur in a high percentage of patients with an infected blood access. Thus, both chronic peritoneal dialysis and chronic hemodialysis continue to be plagued by access problems. Efforts to decrease these problems if successful can result in increased acceptability and safety of both therapies. PMID- 8445846 TI - [The oldest periodicals in pediatrics. From the organization of our periodical]. PMID- 8445845 TI - Mineral metabolism and renal bone disease: effects of CAPD versus hemodialysis. PMID- 8445847 TI - [Relevance of infectious diseases in a pediatric practice]. AB - According to official statistics, infectious diseases only play a minor role in German children. To test this assumption, 1685/3405 charts of a private pediatrician were randomly chosen for further evaluation. 1112/1685 children had been seen in the office during the study period, 934 of them because of an infectious disease (83%). 700/934 charts were further reviewed in a standardized fashion. Pharyngo-tonsillitis was the most frequent diagnosis (18.6%), followed by (non-obstructive) bronchitis (18.5%), infectious diseases of the skin (10.2%) and Otitis media (9.9%). Typical "childhood diseases" (measles, mumps, rubella, varicella) only played a minor role. For some diseases age-specific as well as seasonal changes in incidence could be observed. These data suggest that infectious diseases largely contribute to the morbidity in German children. Prospective epidemiological trials are needed to obtain reliable data for appropriate public health decisions. PMID- 8445848 TI - [Aminoglycosides in patients with mucoviscidosis and pulmonary exacerbation. Comparison of once or three times daily administration]. AB - Twenty-six patients with cystic fibrosis and pulmonary exacerbations were enrolled in a prospective randomized study to compare the efficacy of aminoglycosides (tobramycin or netilmicin) administered once daily (21 episodes, 5 with netilmicin, 16 with tobramycin) and thrice daily (23 episodes, 2 with netilmicin, 21 with tobramycin), respectively. In addition, the patients received an anti-pseudomonal beta-lactam antibiotic. In the single-dose group the total daily dosage was 4.97 +/- 1.12 mg/kg (total dosage per exacerbation: 74.55 mg/kg), compared to 9.60 +/- 2.70 mg/kg in the triple-dose group (total dosage per exacerbation: 165.12 mg/kg). The mean peak and trough serum levels of the aminoglycoside were 8.31 +/- 1.76 mg/l and 0.18 +/- 0.10 mg/l, respectively in the single dose group compared to 6.12 +/- 1.30 mg/l and 0.58 +/- 0.31 mg/l in the triple dose group. Success of treatment, defined as decrease in leucocyte counts, normalization of elevated CRP-values, number of days in hospital and interval until next admission to hospital, was not different between both groups. We conclude that single daily dose of aminoglycosides was as efficacious as triple dose in our patients. PMID- 8445849 TI - [Development of brain atrophy, therapy and therapy monitoring in glutaric aciduria type I (glutaryl-CoA dehydrogenase deficiency)]. AB - Serial trans-fontanellar sonographic examination in a patient with glutaric aciduria type I (GA I) demonstrated that the typical frontotemporal cerebral atrophy developed postnatally within three months paralleling the onset of dystonic symptoms. Pathogenesis of the accompanying macrocephaly remains unclear and can form a diagnostic pitfall. Diet low in lysine and tryptophan led to a dramatic fall in urinary glutaric acid (GA) excretion but as in other patients with GA I did not substantially influence clinical symptoms and course. We determined unchanged levels of GA in plasma and cerebrospinal fluid resulting from variable renal tubular secretion and reabsorption of GA. Monitoring urinary excretion of GA appears inappropriate to control dietary treatment in GA I. Substitutive correction of secondary carnitine depletion seems to protect from deleterious metabolic crises. Treatment with valproic acid resulted in a rise of GABA-concentration in cerebrospinal fluid but did not ameliorate clinical symptoms. This finding is in contrast with the hypothesis that inhibition of cerebral GABA-synthesis by GA is responsible for the development of dystonia in GA 1. Although we observed impressing fluctuation of dystonic symptoms, levodopa did not show therapeutic effects. The extreme variability in the severity of neurologic disease in metabolically identical individuals leads to a "two-hit" hypothesis. PMID- 8445850 TI - [Introduction and critical comparison of clinical scores for characterizing the degree of morbidity of patients with cystic fibrosis]. AB - Scoring systems for evaluation of the degree of severity in patients with cystic fibrosis are critically evaluated. Cross-sectional comparison of Shwachman's score, Cooperman's score, Taussig-NIH score, Bernese score and Huang score reveals that advantages and disadvantages of each score exist. In early days used as a marker of disease progression, later on integrated in research studies for patients survival, the scoring systems loose their power due to the possibility of computerized data storage of unlimited variables. Computerized networking allows immediate access to all measured data of an individual or of groups of patients with detailed criteria. Analysis of such data are less vulnerable for mistakes than individually scored patients data; scoring systems in cystic fibrosis will probably become an historical measure. PMID- 8445851 TI - [Acoustically evoked brain stem potentials in infants with velum clefts]. AB - Brainstem acoustic evoked responses were recorded from 37 infants with cleft palate. Only 35% presented normal auditory thresholds. 27% had a bilateral 22% a unilateral hearing deficit of more than 30 dB. Controls after operative closure of the cleft showed no improvement of the conductive hearing loss. PMID- 8445852 TI - [Microwave stimulated cell marker analysis. Possibilities for more rapid immune diagnosis]. AB - We describe a successful rapid APAAP-complex technique using innovative application of microwave irradiation (MIWI) on Ficoll separated peripheral blood mononuclear cell smears of healthy donors. The typing with several monoclonal antibodies (MoAbs) against different cell surface antigens is compared with the conventional APAAP procedure. The commercial domestic microwave oven was operated at 2.45 GHz. Fifteen second irradiation at 350 W during all incubation steps, e.g. primary antibody, bridging antibody and APAAP-complexes produced excellent color reactions with Fast Red TR, Fast Blue BB, New Fuchsin or NBT similar with the conventional immunoenzyme procedure. The routinely usage of a Silicon-Chamber System developed by us is applicable without limitation under microwave conditions. The results till now have shown that the application of microwave technique (MIWI) eliminated the need for much longer incubation periods without lost of sensitivity. All immunological markers could be detected in the same degree as observed with the conventional method. We could demonstrate that an immunological diagnosis is possible within 30 minutes using air dried smears in an microwave oven. PMID- 8445853 TI - [Genetic aspects of Crohn disease and ulcerative colitis. Empirical risk of recurrence and case presentation]. AB - During the last decades Morbus Crohn and ulcerative Colitis, both chronic inflammatory bowel diseases, show increasing incidence rates. The etiology of the diseases remains unclear. The well known familial occurrence of these diseases will create an increasing demand for medical, psychological and genetic counselling in face of the increasing incidence. The recurrence risks for close relatives will be presented and discussed. An example of Crohn's disease in two twin-siblings illustrates the familial occurrence and underlines the usefulness of being aware of possible recurrence in close relatives. PMID- 8445854 TI - [The 1st Pediatric Clinic of the Budapest Semmelweis Medical University--an area of close German-Hungarian cooperation--from the viewpoint of its medical history treasures]. AB - The First Department of Paediatrics of the University Hospital at Budapest has developed from the fourth children's hospital founded in Europe, and can now look back on over 150 years of history. An amazing amount of significant material has been conserved: books and manuscripts allowing insights into significant periods and events in the history of medicine, clinic records for the years 1839-1850, and very detailed reports on patients treated as in-patients between 1839 and 1841. The author has examined the in-patient reports quite closely and analysed them from the aspects of average length of stay (21.4 days), age groups, diagnoses and courses of illness, finding an overall mortality rate of ("only"!) 20% for all children and of 40% (!) for babies alone. The author describes the valuable contributions made by the hospital's founder. He then discusses the contribution of the founder's two immediate successors, the elder and younger Professor Bokai (father and son), and lists the collections dating from their time in some detail: babies' drinking receptacles, intubation instruments, section protocols, letters and photographs of eminent contemporaries of their throughout the world. He also documents the close cooperation between German and Hungarian paediatricians at this time. PMID- 8445855 TI - [An asphyctic newborn infant with sonographically dilated ventricles]. AB - Brain edema causes severe cerebral defects after perinatal asphyxia. In managing children with asphyxia adequate therapy of brain edema is most important for the neurological outcome. Usually estimation of the width of the ventricular system is initially used for sonographical classification or suspicion of brain edema. We present a case with the unusual aspect of wide cerebral liquor system in spite of severe asphyxia and severe brain edema with consecutive cerebral atrophy. In this case brain edema could only be recognised by the use of doppler sonography of the cerebral vessels and was confirmed by brain pressure monitoring. We therefore suggest that sonographic diagnostic workup of newborns with asphyxia must include a doppler-sonography of the cerebral vessels as well as a brain pressure monitoring. PMID- 8445856 TI - [Congenital tuberculosis in a premature infant]. AB - 5 days after birth a premature baby of 1,300 g (31st week of gestation) was examined, because a congenital tuberculosis was suspected. In the stomach secretion mycobacterium tuberculosis could in fact be found. Abdominal symptoms as well as a post-natal anemia could be lead back to the infection. For three months a double parenteral therapy with INH (10 mg/kg/d) and Rifampicin (10 mg/kg/d) was carried through, then a mono therapy with INH for another 6 months. The bacillus had become resistant to streptomycin. At the beginning of the chemotherapy a cholestasis developed. The tuberculosis could be cured. PMID- 8445857 TI - [Acceleration of epiphyseolysis capitis femoris lenta as a complication of growth hormone therapy in hypophyseal insufficiency]. AB - Slipped capital femoral epiphysis is a rare complication of growth hormone therapy. We report on a young man with pituitary insufficiency, diagnosed and treated with growth hormone at the age of 14 9/12. The patient withdrew from treatment after 6 months of growth hormone therapy without significant catch-up growth or complications. At the age of 21 8/12 years slipping of the left femoral capital epiphysis became apparent 2 1/2 months after treatment with growth hormone had been resumed in combination with low dose testosterone. Young adult patients with unfused epiphyses undergoing growth hormone substitution should be informed that pain in the lower extremities during therapy may be an important sign of a complication of growth hormone therapy. In this age group, patients complaining of pain in the limb should alert the physician to the possibility that a slipped capital femoral epiphysis may be present. PMID- 8445859 TI - [Shortening the working time against unemployment. Work should be better distributed]. PMID- 8445858 TI - [Diarrhea in 1,337 children of the Mainz University Clinic: Importance of Salmonella and rotaviruses]. AB - In Germany, infectious diseases cause little mortality, but they are responsible for a large proportion of morbidity. In order to obtain data about the relevance of infectious diarrhea, the charts of 1337 outpatients, hospitalized for this disorder in the time between 1986-1989 at the Children's Hospital, Johannes Gutenberg University Mainz, were analyzed. Sixty-seven percent of patients were younger than one year. An offending organism could be isolated in 42.1% of patients, with Rotaviruses being the leading cause of diarrhea (415 cases), followed by Salmonella spp. (130 cases). Rotavirus-disease was mainly seen in winter, Salmonella-disease in late summer and in autumn. Severe courses of diarrhea were rare, no patient died. Mean duration of hospitalization was 7 days, independent from the offending organism. Infectious diarrhea is a common disorder in children in Germany, which may lead to hospitalization especially during infancy. Additional epidemiological studies are needed in order to develop effective control measures. PMID- 8445860 TI - [On the way to diploma II. Trans-formation: experience in the service of the future]. PMID- 8445861 TI - [Professional education in Switzerland and relations with the European Economic Community. The recognition is--on principle--assured]. PMID- 8445862 TI - [Reflections. Let us decipher the signs of the time]. PMID- 8445863 TI - [From the psychiatric factory to the therapeutic village?]. PMID- 8445864 TI - [Search for reemployment]. PMID- 8445865 TI - [Quality standards for geriatric nursing]. PMID- 8445866 TI - [Motivation owing to quality work]. PMID- 8445867 TI - [Fewer functional disturbances--better care]. PMID- 8445868 TI - [Transfer of responsibility for the quality of care to the nursing personnel- report of an experience. We ourselves assure the quality of care]. PMID- 8445869 TI - [Development of health services in the canton of Ticino]. PMID- 8445870 TI - [New Red Cross rules. Living through the changes]. PMID- 8445871 TI - [Underpaid nursing personnel--reason for the nursing shortage?]. PMID- 8445872 TI - [What are the potentials of sonography in an intensive care unit?]. PMID- 8445873 TI - [What are the potentials of erythropoietin?]. PMID- 8445875 TI - [What we can clearly see]. PMID- 8445874 TI - [Epidemiology, pathogenesis and prevention of urinary calculi]. PMID- 8445877 TI - [Midwives]. PMID- 8445876 TI - [Hepatitis C. A review on clinical aspects, diagnosis, therapy and prevention]. PMID- 8445878 TI - [Hospital hygiene and environmental protection]. PMID- 8445879 TI - [The nursing process in community nursing]. PMID- 8445880 TI - The etiology and treatment of venous stasis ulcers. PMID- 8445881 TI - Tuberculosis and AIDS in South Carolina: a case-control study. AB - The epidemiologic features of tuberculosis patients with AIDS or HIV infection in this study do not appear to be different from those reported from previous studies. Tuberculosis patients with AIDS or HIV positive antibody in South Carolina are predominantly black males who live in the urban areas and are 25 to 44 years old. They have more extrapulmonary sites and more anergic reactions to tuberculin tests. Physicians and other public health workers should be aware of the abnormal clinical and laboratory manifestations of tuberculosis patients with AIDS and HIV infection. It is also imperative for tuberculosis control programs to offer counseling and HIV antibody testing to tuberculosis patients. PMID- 8445882 TI - Bacterial tracheitis: recognition and treatment. AB - Bacterial tracheitis is a rare, life-threatening form of upper airway obstruction usually seen in children. It is often confused with other forms of upper airway obstruction and must be distinguished from viral croup and epiglottitis. The mainstay of treatment is establishing and maintaining an artificial airway, thus clearing the trachea of the mucopurulent exudate which has accumulated. It is wise for the physician to maintain a high index of suspicion for bacterial tracheitis especially in those children with fever and an upper airway obstruction who fail to exhibit the typical clinical features of croup or epiglottits. PMID- 8445883 TI - Factors which discriminate rural and urban family physicians practicing in South Carolina. AB - A sample of 28 rural and urban private practicing family physicians was compared on a number of attitudes and practice characteristics based on results from a mailed questionnaire. Results cross-validated previous findings and provided new ones. A number of self-report discriminators are discussed to better predict which physicians will locate in rural areas. PMID- 8445884 TI - The white plague returneth. PMID- 8445885 TI - The problems of prescription drug abuse. PMID- 8445886 TI - Elementary mechanics of the endothelium of blood vessels. AB - The endothelium lining human arteries is a continuum of endothelial cells. The flowing blood imposes a shear stress on the endothelium. To compute the internal stress in the endothelium, we use two alternative hypotheses: 1) The cell content is fluid-like so that at steady-state it has no shear stress. 2) The cell content is solid-like. Under hypothesis No. 1, the membrane tension in the upper cell membrane grows in the direction opposite to the blood flow at a rate equal to the blood shear stress. At the junction of two neighboring cells the membrane tension in the downstream cell is transmitted partly to the basal lamina, and partly to the upstream cell. The transmission depends on the osmotic or static pressure difference between the cell and blood. If the static pressure difference is zero, the tension in the upper cell membrane will accumulate upstream. At other values of static pressure, the cell membrane tension may increase, decrease, or fluctuate along the vessel depending on the inclination of the side walls of the cells at the junctions. To determine the sidewall inclinations, we propose to use the complementary energy theorem. Under hypothesis No. 2, the cell content can bear shear, which tends to reduce the cell membrane tension; but the cell membrane tension accumulation phenomenon discussed above remains valid. These results are used to analyze the interaction of the cell membrane and cell nucleus; and the effect of turbulences in the flow on causing large fluctuations in cell membrane tension and vertical oscillations of the nuclei. The implication of tensile stress on the permeability of the cell membrane is discussed. We conclude that for the study of mass transport and stress fibers in the endothelial cells, one should consider the interaction of neighboring endothelial cells as a continuum, and shift attention from the shear stress in the blood to the principal stresses in the cells. PMID- 8445888 TI - A numerical simulation of flow in a two-dimensional end-to-side anastomosis model. AB - In order to understand the possible role that hemodynamic factors may play in the pathogenesis of distal anastomotic intimal hyperplasia, we carried out numerical simulations of the flow field within a two-dimensional 45 degree rigid-walled end to-side model anastomosis. The numerical code was tested and compared with experimental (photochromic dye tracer) studies using steady and near-sinusoidal waveforms, and agreement was generally very good. Using a normal human superficial femoral artery waveform, numerical simulations indicated elevated instantaneous wall shear stress magnitudes at the toe and heel of the graft-host junction and along the host artery bed. These sites also experienced highly variable wall shear stress behavior over the cardiac cycle, as well as elevated spatial gradients of wall shear stress. These observations provide additional evidence that intimal hyperplasia may be correlated to wall shear stresses over the cardiac cycle, high wall shear stress gradients, or a combination of the three. The limitations of the present work (especially in regard to the two dimensional nature of the flow simulations) are discussed, and results are compared to previous observations about distal anastomotic intimal hyperplasia. PMID- 8445887 TI - Hemodynamic patterns in two models of end-to-side vascular graft anastomoses: effects of pulsatility, flow division, Reynolds number, and hood length. AB - Flow behavior in models of end-to-side vascular graft anastomoses was studied under steady and pulsatile flow conditions. Models were constructed to simulate geometries employed in experimental studies on intimal thickening in a canine model. Reynolds numbers, division of flow in the outflow tracts and the pulsatile waveform employed were taken from measurements obtained in the canine model. Flows in the scaled-up, transparent models were visualized with white, neutrally buoyant particles which were photographed under laser illumination and also recorded on video tape under bright incandescent light. Strong, three-dimensional helical patterns which formed in the anastomotic junction were prominent features of the flow fields. Regions of low wall shear, oscillatory wall shear and long particle residence time were identified from the flow visualization experiments. Comparisons with the limited qualitative data available on intimal thickening in vascular graft anastomoses suggest a relation between localization of vascular intimal thickening and those surfaces experiencing low shear and long particle residence time. PMID- 8445889 TI - Improved Cartesian coordinate finite difference simulations of small cylindrical objects. AB - An analytical, cylindrical coordinate formula for the thermal resistance around small cylindrical objects has been incorporated into finite difference equations in Cartesian coordinates to improve the accuracy of the numerical simulations of hyperthermia cancer treatments. This is done by introducing a circular finite difference control volume which is centered on the cylindrical object. The temperature distributions calculated from this new formulation and from the formulation obtained from a conventional, rectangular control volume are compared to the predictions from an analytical solution. The results show that for a given Cartesian grid spacing, the new method is superior to the conventional one. This will allow more accurate numerical solutions to be obtained at larger grid spacings when the effect of blood vessels or other cylindrical objects, such as ferromagnetic implants, hot water tubes, etc., are being investigated. PMID- 8445890 TI - Design and development of a new general purpose stereotaxic device. AB - This paper describes the design and development of a new device which allows the surgeon to locate an internal point following two X-ray views with an image intensifier. Three dimensional coordinates of the target point are directly estimated by means of two ring-and-bead sights and no computer calculations are necessary. After the location of the target point it is possible to choose any track to it by means of the rotation of an arc and the circumferential sliding of the arc. The system reduces radiation doses and it can be used for many purposes such as percutaneous discectomies and chemonucleolysis, biopsies and screw insertion of interlocking nails. PMID- 8445891 TI - Factors in the initiation and propagation of aortic dissections in human autopsy aortas. AB - Our goal was to evaluate physical factors in the initiation and propagation of dissections in human aortas. Aortic dissection was simulated in 21 open unpressurized human autopsy aortas by infusing dyed isotonic saline into the media at constant flow. Pressure during growth of the fluid filled cavity was monitored and correlated with volume to give pressure-volume curves, from which distensibility, peak pressure, and work data were calculated. Dissections in specimens occurred at a very high nonphysiological mean pressure of 79 +/- 29 (SD) kPa (596 +/- 214 mmHg). Age and tear depth had no significant effect on medial strength of human aortas but sex, location and atherosclerotic plaque formation did (p < 0.05). The mean pressure value for the female abdominal fibrous/calcified group (92 +/- 30 kPa, 691 +/- 222 mmHg) differed from that of the male abdominal fibrous/calcified group (69 +/- 36 kPa, 508 +/- 269 mmHg). We also observed a significant difference between the male thoracic fibrous calcified (80 +/- 31 kPa, 601 +/- 230 mmHg) and male abdominal fibrous/calcified (68 +/- 36 kPa, 508 +/- 269 mmHg) groups. Significant differences were observed between the female fatty/normal (75 +/- 25 kPa, 562 +/- 187 mmHg) and fibrous/calcified (91 +/- 23 kPa, 685 +/- 176 mmHg) groups of the thoracic aorta and between the male fatty/normal (86 +/- 23 kPa, 650 +/- 169 mmHg) and fibrous/calcified (68 +/- 36 kPa, 508 +/- 269 mmHg) groups of the abdominal aorta. Distensibility data showed no trends. It is probable that dissection does not occur spontaneously in the absence of a connective tissue disorder and/or surgical procedure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8445892 TI - Dispersion and uptake in a coiled tube. AB - We have investigated the dispersion characteristics of a highly soluble tracer gas in a coiled tube lined with wet gelatine. Our experiments indicate that absorption and desorption of the gas at the wall dominates tracer dispersion along the tube. The results confirm previous experiments in a branching geometry indicating that the influence of secondary flows on dispersion is reduced if the tracer is very soluble in the wall. PMID- 8445893 TI - Mechanical and electrical responses of the squid giant axon to simple elongation. AB - There is a limited amount of information available on the mechanical and functional response of the nervous system to loading. While deformation of cerebral, spinal, or peripheral nerve tissue can have particularly severe consequences, most research in this area has concentrated on either demonstrating in-vivo functional changes and disclosing the effected anatomical pathways, or describing material deformations of the composite structure. Although such studies have successfully produced repeatable traumas, they have not addressed the mechanisms of these mechanically induced injuries. Therefore, a single cell model is required in order to gain further understanding of this complex phenomena. An isolated squid giant axon was subjected to controlled uniaxial loading and its mechanical and physiological responses were monitored with an instrument specifically designed for these experiments. These results determined that the mechanical properties of the isolated axon are similar to those of other soft tissues, and include features such as a nonlinear load-deflection curve and a hysteresis loop upon unloading. The mechanical response was modeled with the quasi-linear viscoelastic theory (Fung, 1972). The physiological response of the axon to quasi-static loading was a small reversible hyperpolarization; however, as the rate of loading was increased, the axon depolarized and the magnitude and the time needed to recover to the original resting potential increased in a nonlinear fashion. At elongations greater than twenty percent an irreversible injury occurs and the membrane potential does not completely recover to baseline. PMID- 8445894 TI - Effects of stress shielding on the mechanical properties of rabbit patellar tendon. AB - Mechanical properties of the stress-shielded patellar tendon were studied in the rabbit knee. Stress shielding was accomplished by stretching a stainless-steel wire installed between the patella and tibial tubercle and thus, releasing the tension in the patellar tendon completely. Tensile tests were carried out on the specimens obtained from the patellar tendons which were exposed to the stress shielding for 1 to 6 weeks. The stress shielding changed the mechanical properties of the patellar tendon significantly: it decreased the tangent modulus and tensile strength to 9 percent of the control values after 3 weeks. There was a 131 percent increase in the cross-sectional area and a 15 percent decrease in the tendinous length. Remarkable changes were also observed in the structural properties: for example, the maximum load of the bone-tendon complex decreased to 20 percent of the control value after 3 weeks. Histological studies showed that the stress shielding increased the number of fibroblasts and decreased the longitudinally aligned collagen bundles. These results imply that if no stress is applied to the autograft in the case of augmentative reconstruction of the knee ligament, the graft strength decreases remarkably. PMID- 8445895 TI - Mechanical performance of external fixators with wires for the treatment of bone fractures--Part I: Load-displacement behavior. AB - Using matrix algebra, a mathematical model is formulated for a particular type of external fixator with wires (system developed by Ilizarov) for the treatment of bone fractures. The mathematical model is used to give a linear estimate of the stiffness under lateral and axial loads in a representative number of practical conditions. Relative displacements of the bone ends at the fracture site are calculated not only in the common case of a gap, but also for various angles of inclined sliding contact; in this case, a realistic load is applied and nonlinear stiffening of the wires under transversal loads is iteratively taken into account. PMID- 8445896 TI - Mechanical performance of external fixators with wires for the treatment of bone fractures--Part II: Wire tension and slippage. AB - The work shows correct procedures needed in order to gather reliable data from measurement of displacements versus axial load in a laboratory mounting of the Ilizarov external fixator. The mechanism of settling after load cycling is investigated. Detension under load is a major problem of wires. By means of vibration frequency measurements, tests on single wire allow determination of reduction in wire tension due to transverse loading: it is found that, almost independently from the amount of clamp tightening, the tension reaches a lower limit related only to the transverse load and not related to pretension. It is shown that, for higher clamp tightening torques, wire detension must be attributed to permanent plastic deformation of the wires; moreover, it is shown that the unavoidable errors in the spacing of the tensioned wires lead to marked decrease of their stiffness under transverse load. PMID- 8445897 TI - The volume of motion: introduction, derivation, and an application comparing various spinal fixation devices. AB - Range of motion (ROM), the displacement between two limits, is one of the most common parameters used to describe joint kinematics. The ROM is a one-dimensional parameter, although the motion at many normal and pathological joints is three dimensional. Certainly, the ROM yields vital information, but an overall measure of the three-dimensional mobility at a joint may also be useful. The volume of motion (VOM) is such a measure. The translational VOM is the volume defined by all possible ROMs of a point on a rigid body. The rotational VOM, although its interpretation is not as tangible as the translational VOM, is a measure of the three-dimensional rotational mobility of a rigid body. The magnitude of the VOM is proportional to mobility; the VOM is a scaler, which does not contain any directional information. Experimental determination of the VOM is not practical since it would require applying loads in an infinite number of directions. The mathematical derivation given here allows the VOM to be calculated, with the assumption of conservative elasticity, from the resultant displacements of three distinct load vectors of equal magnitude. An example of the VOM is presented in the comparison of the biomechanical stabilizing potential of various spinal fixation devices. PMID- 8445898 TI - Measurement of the impulsive bone motion by skin-mounted accelerometers. AB - A measurement system was designed to investigate longitudinal wave propagation through the lower extremity generated from foot strikes. The principal goal of the design was to eliminate measurement time lag and amplitude reduction, such that the acceleration measured by Skin Mounted Accelerometer--SMA is equal to the actual acceleration of the bone measured by Bone Mounted Accelerometer--BMA. For accurate dynamic measurement, it is important that the gain and phase of the measurement system are as close as possible to a constant and zero, respectively, for the frequency range being covered. An in vitro experiment was carried out to simultaneously measure skin and bone accelerations. The obtained information was used for identification of a linear spring/damper model representing the interface between the BMA and the SMA. The present work showed that the SMA overestimated the BMA by 12 percent in the signals between 15-30 Hz. PMID- 8445899 TI - The kinematometer--an integrated kinematic sensor for kinesiological measurements. AB - The calculation of human joint forces and moments during locomotion is usually based on the solution of the "inverse dynamics problem." A new approach, called the Integrated Kinematic Sensor (IKS) approach, is proposed. It combines measurements of position, linear acceleration and angular velocity, coupled with six degrees of freedom analysis of rigid body motion, for the purpose of deriving high quality link kinematics and joint loads (force and moment) estimates. The IKS approach is tested on an instrumented compound pendulum to simulate the swing of a lower limb segment. The results show a high degree of correlation between the loads estimated by the IKS and those directly measured by the instrumented joint. The approach is illustrated by studying the kinematic and dynamic variables of the human shank segment during normal walking. The results agree with the basic patterns reported in the literature, while adding new information on transients during heel strike and toe off. PMID- 8445900 TI - Comparison of the adjoint and influence coefficient methods for solving the inverse hyperthermia problem. AB - An adjoint formulation is derived and used to determine the elements in the Jacobian matrix associated with the inverse problem of estimating the blood perfusion and temperature fields during hyperthermia cancer treatments. This method and a previously developed influence coefficient method for obtaining that matrix are comparatively evaluated by solving a set of numerically simulated inverse hyperthermia problems. The adjoint method has the advantage of requiring fewer solutions of the bioheat transfer equation to estimate the Jacobian than does the influence coefficient method when the number of measurement sensors is significantly smaller than the number of unknown parameters. Thus, it could be a preferable method to use in hyperthermia applications where the number of sensors is strictly limited by patient considerations. However, the adjoint method requires that CPU time intensive convolutions be numerically evaluated. Comparisons of the performance of the adjoint formulation and the influence coefficient method show that, first, there is a critical ratio of the number of measurement sensors to the number of unknown parameters at which the CPU time per iteration required to calculate the Jacobian matrix is the same for both methods. The adjoint method is faster than the influence coefficient method only when the value of the ratio is less than that critical value. For the hyperthermia problems investigated in the present study, this only occurs for cases with a very small number of measurement sensors. This presents a potential problem for clinical applications because the fewer measurement sensors used, the less information that can be gathered to correctly solve the inverse problem.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8445901 TI - Mechanics of active contraction in cardiac muscle: Part I--Constitutive relations for fiber stress that describe deactivation. AB - Constitutive relations for active fiber stress in cardiac muscle are proposed and parameters are found that allow these relations to fit experimental data from the literature, including the tension redeveloped following rapid deactivating length perturbations. Contraction is driven by a length-independent free calcium transient. The number of actin sites available to react with myosin is determined from the total number of actin sites (available and inhibited), free calcium and the length history-dependent association and dissociation rates of two Ca2+ ions and troponin as governed by a first-order, classical kinetics, differential equation. Finally, the relationship between active tension and the number of available actin sites is described by a general cross-bridge model. Bridges attach in a single configuration at a constant rate, the force within each cross bridge varies linearly with position, and the rate constant of bridge detachment depends both on position and time after onset of contraction. In Part II, these constitutive relations for active stress are incorporated in a continuum mechanics model of the left ventricle that predicted end-systolic transmural strain distributions as observed experimentally. PMID- 8445902 TI - Mechanics of active contraction in cardiac muscle: Part II--Cylindrical models of the systolic left ventricle. AB - Models of contracting ventricular myocardium were used to study the effects of different assumptions concerning active tension development on the distributions of stress and strain in the equatorial region of the intact left ventricle during systole. Three models of cardiac muscle contraction were incorporated in a cylindrical model for passive left ventricular mechanics developed previously [Guccione et al. ASME Journal of Biomechanical Engineering, Vol. 113, pp. 42-55 (1991)]. Systolic sarcomere length and fiber stresses predicted by a general "deactivation" model of cardiac contraction [Guccione and McCulloch, ASME Journal of Biomechanical Engineering, Vol. 115, pp. 72-81 (1993)] were compared with those computed using two less complex models of active fiber stress: In a time varying "elastance" model, isometric tension development was computed from a function of peak intracellular calcium concentration, time after contraction onset and sarcomere length; a "Hill" model was formulated by scaling this isometric tension using the force-velocity relation derived from the deactivation model. For the same calcium ion concentration, the sarcomeres in the deactivation model shortened approximately 0.1 microns less throughout the wall at end-systole than those in the other models. Thus, muscle fibers in the intact ventricle are subjected to rapid length changes that cause deactivation during the ejection phase of a normal cardiac cycle. The deactivation model predicted rather uniform transmural profiles of fiber stress and cross-fiber stress distributions that were almost identical to those of the radial component. These three components were indistinguishable from the principal stresses. Transmural strain distributions predicted at end-systole by the deactivation model agreed closely with experimental measurements from the anterior free wall of the canine left ventricle. PMID- 8445903 TI - An experimental model of gas dispersion and uptake at the bronchial wall. AB - Dispersion and uptake of gas boli of a range of solubilities was examined in lung airway models; first a straight tube, then a four generation network. Airway liquid lining was simulated with gelatin. The bolus dispersion was determined from the first three moments of the concentration profile measured at two positions down-stream. The disruption of the flow by the bifurcations significantly reduces the dispersion of an insoluble gas, compared to that predicted in an equivalent network of parallel straight tubes. Retention of gas in the wall increases with solubility causing increased bolus dispersion and decreased average speed. For highly soluble gases this process dominates and the effect of bifurcations becomes less significant. PMID- 8445904 TI - The effects of curvature on fluid flow fields in pulmonary artery models: flow visualization studies. AB - In vitro pulsatile flow visualization studies were conducted to assess the effects of varying radii of curvature of the right ventricular outflow tract (RVOT) and main pulmonary artery (MPA) on the flow fields in the main, right, and left pulmonary arteries of a one month lamb pulmonary artery model. Three glass flow-through models were studied; one with no curvature, one with the correct anatomic curvature, and one with an overaccentuated curvature on the RVOT and MPA. All other geometric parameters were held constant. Pulsatile flow visualization studies were conducted at nine flow conditions; heart rates of 70, 100, and 140 bpm, and cardiac outputs of 1.5, 2.5 and 3.5 l/min with corresponding mean pulmonary pressures of 10, 20, and 30 mmHg. Changes were observed in the pulmonary flow fields as the curvature of the outflow tract, heart rate and mean pulmonary pressure were varied. An increase in vessel curvature led to an increase in the overall radial nature of the flow field as well as flow separation regions which formed faster, originated further downstream, and occupied more of the vessel area. At higher heart rates, the maximum size of the separation regions decreased, while flow separation regions appeared earlier in the cardiac cycle and grew more quickly. Heart rate also affected the initiation of flow reversal; flow reversal occurred later in the cardiac cycle at lower heart rates. Both heart rate and mean pulmonary pressure influenced the stability of the pulmonary flow field and the appearance of coherent structures. In addition, an increase in mean pulmonary pressure increased the magnitude of reverse flow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8445905 TI - An analysis of patient characteristics for methicillin-resistant Staphylococcus aureus colonization and infection in a hospital population. PMID- 8445906 TI - Superior mesenteric artery repair following penetrating trauma. AB - Superior mesenteric artery injuries remain a challenge to even the most experienced trauma surgeon and continue to carry a significant mortality in spite of aggressive management. If possible, primary arteriorrhaphy should be performed, as mortality has been shown to increase with more complex methods of repair. This probably emphasizes the severity of the vascular injury and hemorrhagic complications rather than the complications of the repair itself. PMID- 8445907 TI - Thrombotic episodes. PMID- 8445908 TI - From lab tests to lawsuits: improving physician-patient communication. TMA Communications and Public Service Committee. PMID- 8445909 TI - Oak Ridge Health Studies Agreement. PMID- 8445910 TI - Deadly delay. PMID- 8445911 TI - Address of the AMA president. PMID- 8445912 TI - With one voice. PMID- 8445914 TI - Ethical and judicial considerations. PMID- 8445913 TI - A New Year's retrospective, or, a tremulous look down the pike. PMID- 8445915 TI - Primary hepatic actinomycosis--diagnosis by percutaneous transhepatic needle aspiration. PMID- 8445916 TI - Endoscopic surveillance of Barrett's esophagus. Does it help? AB - Patients with Barrett's esophagus are recognized as having a high risk of development of adenocarcinoma. Although endoscopic surveillance of these patients is commonly practiced, its benefits have not been proved. This study was undertaken to examine the effect of endoscopic surveillance on the stage of resected carcinoma arising in Barrett's esophagus and the effect on postoperative survival. Between 1973 and 1991, 77 patients with adenocarcinoma were seen by us, and 19 of them were under endoscopic surveillance. The 19 patients underwent endoscopic biopsies at 1-month to 4-year intervals (median 6 months). All but one patient underwent esophagogastrectomy when severe dysplasia or invasive carcinoma was detected. The stages of the resected carcinomas in the group under surveillance compared with the group not under surveillance were significantly different, 58% of the patients under surveillance having stages 0 and I disease and 21% having stage III disease compared with 17% of the patients not under surveillance having stages 0 and I disease and 47% having stage III disease (p = 0.006). The 5-year actuarial survival of patients undergoing routine surveillance was 62% and of patients not under surveillance, 20% (p = 0.007). Endoscopic surveillance of patients with benign Barrett's esophagus permits detection of carcinoma at an early stage and improves long-term survival after resection for severe dysplasia and invasive carcinoma. PMID- 8445917 TI - Thoracoscopic stapled resection for spontaneous pneumothorax. AB - Video-assisted thoracoscopy has recently evolved as an alternative to thoracotomy for several thoracic disorders. Spontaneous pneumothorax may be ideally suited for thoracoscopic management. Stapling of apical blebs and pleurodesis or pleurectomy can now be performed thoracoscopically in a fashion identical to the standard operation done through a lateral or axillary thoracotomy. We compared our results with thoracoscopic management of spontaneous pneumothorax in 26 patients (group I) with a group of 20 patients previously subjected to axillary thoracotomy (group II). Indications for operation, sex distribution, and average age (group I, 32.3 years; group II, 33.7 years) were comparable. Hospital stay was less in group I (2.88 +/- 0.99 days versus 4.47 +/- 1.07 days; p = 0.07), as was the use of parenteral narcotics after 48 hours (2/26 = 7.7% versus 14/20 = 70%; p = 0.01). There have been no recurrences to date (mean follow-up, 8 months) in the thoracoscopic group. Video-assisted thoracoscopic management of spontaneous pneumothorax allows performance of the standard surgical procedure while avoiding the thoracotomy incision. Video-assisted thoracoscopic management is safe and offers the potential benefits of shorter hospital stays and less pain. PMID- 8445918 TI - Management and prognosis of massive hemoptysis. Recent experience with 120 patients. AB - A retrospective analysis was done of 120 consecutive patients with life threatening hemoptysis (greater than 200 ml of discharge per 24 hours) cared for between 1983 and 1990 at our institution. Seventy-nine percent of the patients (95/120) had hemoptysis exceeding 500 ml/24 hr. Inflammatory lung disease was the underlying cause in at least 85% of cases (n = 103); and of these, pulmonary tuberculosis was the primary diagnosis in 85% (88/103). Fifty-two patients (43%) had had a prior episode of massive hemoptysis, usually within 3 months of their admission. Urgent examination with rigid endoscope in 97 patients (81%) localized the bleeding in only 42 (43%). The overall hospital mortality rate was 10% (12/120) and was similar for those having pulmonary resection (7.1%, 3/42), and those assisted medically (11.5%, 9/78) (p = not significant). However, of these hospital survivors on whom 6-month follow-up was available, 36.4% (20/55) of those with medical management and none (0/39) (p < 0.001) of those with surgical management had recurrent massive hemoptysis. Forty-five percent of these cases were fatal. Current management of massive hemoptysis has resulted in improved hospital outcome. However, the high risk of recurrent and often fatal hemoptysis mandates the definitive management of the bronchial arteries before discharge from the hospital. Recent reports suggest that percutaneous embolization may be effective in nonsurgical candidates. PMID- 8445919 TI - Staged Fontan operation for complex cardiac anomalies with subaortic obstruction. AB - Ventricular hypertrophy is a recognized risk factor for the Fontan operation in cases of complex cardiac anomalies with unrestricted pulmonary blood flow and subaortic obstruction. Between 1986 and 1991 we have treated 23 such patients with a new type of palliation combining a main pulmonary artery-ascending aorta anastomosis with a bidirectional cavopulmonary anastomosis. Their ages averaged 57 +/- 36 months (7 to 155 months). Nine patients had (S,L,L) single ventricule with transposition and the other 14 had more complex cardiac anomalies unsuitable for biventricular repair. Subaortic obstruction was defined by a hemodynamic criterion (n = 6) or by a morphologic criterion (n = 17). There were five hospital deaths (21.7%): All three patients older than 7 years of age died (p = not significant). Follow-up averaged 28 +/- 21 months (range 1 to 58 months). Among the 18 hospital survivors, the proportions surviving 1 and 5 years after the operation were 78% and 63%, respectively. Control cardiac catheterization in 11 patients showed no or trivial subaortic gradient, a mean cavopulmonary pressure of 10 +/- 3 mm Hg, and a mean arterial oxygen saturation of 83%. Nine patients underwent secondary Fontan repair in our institution 21 +/- 4 months after palliation, without deaths. Another patient died elsewhere, 3.7 years after palliation, as a result of hemorrhage at sternal reentry during attempted Fontan operation (overall mortality at repair, 10%). The other eight patients are awaiting Fontan operation. This staged approach reduces both pressure and volume ventricular load and provides adequate oxygenation before the Fontan operation. In our experience, it resulted in reduced mortality at definitive repair. PMID- 8445920 TI - Outcomes in neonatal pulmonary atresia with intact ventricular septum. A multiinstitutional study. AB - A total of 171 neonates with pulmonary atresia and intact ventricular septum were entered into a prospective multiinstitutional study between January 1, 1987, and January 1, 1991. Treatment was not assigned randomly but was selected by the responsible physicians. The Z-value (standard deviation units) of the diameter of the tricuspid valve was less than -2 in 52% of patients and less than -4 in 26%; it was highly correlated with right ventricular cavity size (which was small in 90% of patients and was severely reduced in 54%). Coronary artery-right ventricular fistulas were present in 45% of patients, and right ventricular dependency was severe in 9%; diameter (Z-value) of the tricuspid valve was negatively correlated (P < 0.0001) with the prevalence of both. Survival was 81% at 1 month after the first intervention and 64% at 4 years; the hazard function (instantaneous risk of death) declined rapidly after the initial procedure but remained appreciable for 24 months. Multivariable analysis showed small diameter of the tricuspid valve, severe right ventricular coronary dependency, birth weight, and the date and type of initial procedure to be risk factors for time related death. Subsequent procedures were performed in 51% of patients. Among patients undergoing an initial procedure that did not include a systemic pulmonary artery shunt, only 49% did not receive a shunt in the subsequent 1 month; small size of the tricuspid valve was the only risk factor for receiving the subsequent shunt. Ninety-eight percent of living patients whose initial procedure did not include a transannular patch were free of a subsequently placed transannular patch within 1 month, but only 45% were free of it 3 years later; no risk factors were identified. Eighteen percent of living patients had received a one-ventricle repair within 3 years, and 32% had received a two-ventricle repair; the remainder (50%) had incompletely separated pulmonary and systemic circulations. The only patient-specific risk factor for not receiving a two ventricle repair was the Z-value of the tricuspid valve. PMID- 8445921 TI - Prosthetic valve endocarditis. Experience with porcine bioprostheses. AB - Prosthetic valve endocarditis remains an infrequent but serious complication of cardiac valvular replacement. Prosthetic valve endocarditis was diagnosed in 56 (1.8%) of 3200 patients in whom one or more porcine bioprostheses were implanted between 1975 and 1988. Of the 56 patients with prosthetic valve endocarditis, there were 40 men and 16 women, with a mean age at initial implantation of 57 years (27 to 81 years). Of the 56 patients, 6 were initially treated for native valve endocarditis. There were 8 cases of early prosthetic valve endocarditis (defined as occurring less than 60 days after initial surgical intervention) and 48 cases of late prosthetic valve endocarditis (occurring after 60 days). The overall mortality rate of the 56 patients was 32% (18 patients). Of the 8 patients with early prosthetic valve endocarditis, 6 (75%) died. Of the 48 patients with late prosthetic valve endocarditis, 12 (25%) died. The predominant organisms were Staphylococcus epidermidis (12 cases), Streptococcus viridans (8 cases) and Staphylococcus aureus (7 cases). The presence of hemodynamic compromise, including congestive heart failure, septic embolism, persistent sepsis, and echocardiographic evidence of vegetations, dictated the mode and timing of the addition of surgical intervention to medical therapy. The survival rate for medically and surgically treated patients with late prosthetic valve endocarditis was 91% (20 patients); none of the patients with early prosthetic valve endocarditis survived (all had severe hemodynamic compromise). We analyzed 18 factors for the prediction of early and late death. The predictors of death by univariate analysis for both early and late prosthetic valve endocarditis were age, diagnosis time, renal status, sepsis, management mode, fever, dental procedures, and dental prophylaxis. The predictors by multivariate analysis were age, diagnosis time, renal status, and management mode for early prosthetic valve endocarditis, and only diagnosis time for late prosthetic valve endocarditis. Annular abscess formation occurred in 27% of the patients. There were no complex aortic or mitral reconstructions. There was one reoperation for recurrent and residual endocarditis. There was one late death as a result of recurrent prosthetic valve endocarditis. We advocate early diagnosis and aggressive combined medical and surgical treatment before the development of hemodynamic compromise and other characteristic signs when the culprit organisms are Staphylococcus aureus, gram-negative organisms, and Candida albicans. PMID- 8445922 TI - Remodeling of the aortic valve anulus. AB - Isolated aortic valve regurgitation that results from disease that primarily affects the aortic wall can be repaired by remodeling of the aortic anulus to restore its normal geometry. This involves excision of the aortic wall to within 2 to 3 mm of the leaflet attachments, detachment of the coronary ostia, reshaping of the anulus with the aid of a Dacron graft, and then reimplantation of the coronary arteries. Increases in the surface area of the leaflet that are caused by root dilatation are often present and can be accommodated in the repair procedure. In this study we describe our experience with 10 patients with annuloaortic ectasia who underwent the remodeling procedure at the National Heart Hospital and the Royal Brompton Hospital from 1982 to 1990. PMID- 8445923 TI - Pathogenesis of ischemic mitral insufficiency. AB - We developed a new animal model of ischemic mitral insufficiency in sheep and used it to test the hypothesis that the combination of posterior papillary muscle infarction and left ventricular dilatation was required to produce mitral regurgitation after acute inferior myocardial infarction of moderate size. In 12 sheep, ligation of the first two circumflex marginal coronary arteries infarcted 23% of the left ventricular mass, increased left ventricular cavitary area from 13.2 +/- 1.2 cm2 to 20.0 +/- 2.7 cm2 by 8 weeks and did not produce ischemic mitral regurgitation. In 13 sheep, ligation of the second and third circumflex marginal arteries infarcted 21% of the left ventricular mass and, in 11 of these sheep, the posterior papillary muscular mass as well. When the papillary muscle was included, this infarction produced progressively severe mitral regurgitation over 8 weeks, as left ventricular cavitary area increased from 12.5 +/- 2.6 cm2 to 22.8 +/- 3.8 cm2. We conclude that neither posterior papillary muscle infarction nor left ventricular dilatation alone produces ischemic mitral regurgitation after moderate-sized inferior wall infarction, but that the combination does. PMID- 8445924 TI - Selection of patients for same-day coronary bypass operations. AB - Between March 15, 1990, and December 31, 1991, we admitted to the Virginia Mason Hospital for isolated coronary bypass operations 175 consecutive patients with chronic, stable angina pectoris who had prior coronary arteriography. One hundred patients were admitted on the same day as their operations, and 75 patients, deemed to be at higher risk, were admitted 1 day before the operation. Postoperative progress of all patients was monitored by means of a clinical pathway form with physiologic and activity measures plotted against postoperative days. We found no difference in age, sex, or total number of comorbidity factors. Diabetes and ejection fraction less than 0.50 were significantly more common in preoperatively admitted patients and were independently predictive of admitting group. Significant differences between surgeons in the proportion of same-day patients admitted could not be explained by differences in common risk factors. There was no significant difference in postoperative major or minor complications or number of clinical pathway deviations, but two deaths occurred in patients admitted preoperatively. Average total hospital stay was 1 1/2 days less for same day patients, a highly significant difference. Total hospital charges averaged $19,000 for the series and were $286 more for preoperatively admitted patients, a difference that was not statistically significant. Patients admitted selectively for same-day coronary bypass are not at risk for an increased number of complications. Although their hospital stay is reduced, the reduction of their hospital charges is minimal. Preoperative admission of patients with comorbidity requiring medical management or with physical incapacity remains justified, and admitting decisions should remain with the operating surgeon, not third parties. PMID- 8445925 TI - Experience with an implantable tiered therapy device incorporating antitachycardia pacing and cardioverter/defibrillator therapy. AB - The implantable cardioverter-defibrillator provides an alternative therapy for medically refractory ventricular tachyarrhythmias in patients who are not candidates for ventricular operations or in whom these operations have failed. Currently, however, available devices have limitations. In this report we describe our experience with a programmable, tiered therapy device with anti ventricular tachyarrhythmia pacing and VVI pacing capabilities (Cadence V-100, Ventritex Inc., Sunnyvale, Calif.). This device offers certain advantages compared with conventional implantable cardioverter-defibrillators: (1) tiered, anti-ventricular tachyarrhythmia therapy incorporating programmable, rate adaptive burst pacing in addition to energy-programmable cardioversion/defibrillation, (2) biphasic cardioversion/defibrillation waveforms, resulting in lower defibrillation thresholds, (3) the ability to abort therapy for nonsustained ventricular tachyarrhythmias, (4) electrogram storage of detected events for later retrieval and analysis, (5) noninvasive, device generated programmed stimulation for system testing, and (6) backup VVI pacing capability. Forty patients (aged 14 to 79 years) with ventricular tachyarrhythmias refractory to medical therapy received this device. The mean left ventricular ejection fraction was 33% +/- 16%. Preoperative electrophysiologic testing revealed inducible monomorphic ventricular tachyarrhythmia responsive to rapid ventricular pacing in 36 patients (90%). An extrapericardial two-patch configuration was used with either epicardial screw-in or bipolar endocardial sensing/pacing wires. No operative mortality and no device related infection occurred. During a follow-up period of 16 +/- 7 months (range 3 to 30 months), 38 patients remained active with the implanted device; one patient died of congestive heart failure 4 months after implantation, and the system was explanted in one patient who underwent cardiac transplantation. In 33 patients a total of 1815 ventricular tachyarrhythmias were detected that resulted in therapy. Rate-adaptive burst pacing was used as the initial therapy in 1470 episodes and was successful in 1352 instances (92%). Pacing-induced ventricular tachyarrhythmia acceleration occurred in 4% of episodes. The remaining ventricular tachyarrhythmia episodes were treated with cardioversion. In 18 patients (45%) cardioversion therapy was aborted after spontaneous termination of ventricular tachyarrhythmia.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8445926 TI - Bronchial circulation after experimental lung transplantation. The effect of long term administration of prednisolone. AB - The effect of corticosteroids on bronchial healing after modified left lung transplantation was investigated in pigs. In groups I (n = 6) and II (n = 6), animals received cyclosporine (15 mg/kg per day) and azathioprine (2 mg/kg per day). In group II, prednisolone (1 mg/kg per day) was also administered. Bronchial blood flow was estimated at the donor carina and donor second carina with laser Doppler velocimetry and radioisotopes 7 days postoperatively; macroscopic and microscopic assessments of graft airways were performed. Bronchial blood was calculated relative to the recipient carina. In group II, bronchial blood flow at the donor carina and donor second carina was significantly higher than that of group I. Macroscopic assessment revealed more pronounced ischemic changes in group I (5 of 6 animals) than in group II (2 of 6 animals, p = not significant). Microscopically, airway samples from the donor carina revealed marked destructive changes in five of six animals in group I. In group II, only mild ischemic changes, which were limited to the respiratory epithelium, were seen. We concluded that the administration of prednisolone results in improved bronchial blood flow and decreased bronchial ischemia after lung transplantation. PMID- 8445927 TI - Changes in alveolar oxygen and carbon dioxide concentration and oxygen consumption during lung preservation. The maintenance of aerobic metabolism during lung preservation. AB - The lung is the only organ to which oxygen may be supplied after its blood supply is stopped. Before this study, we were not certain whether lung cells were able to maintain aerobic metabolism with the oxygen in the alveoli during preservation. Excised rabbit lungs were used to measure changes in the concentration of oxygen and carbon dioxide in the airway and changes in glucose, glucose-6-phosphate, lactate, adenosine triphosphate, and phosphocreatine levels in the lung tissue during preservation under different conditions. Twenty-seven lungs were flushed with low-potassium dextran electrolyte solution, inflated with room air, and preserved at 1 degree C (n = 8), 10 degrees C (n = 8), or 22 degrees (n = 11) for 4, 12, or 24 hours. Eight additional lungs were inflated with 100% nitrogen and preserved at 10 degrees C for 4 (n = 4) or 24 (n = 4) hours. Oxygen levels decreased and carbon dioxide levels increased in the airway of the lungs that were inflated with room air at rates dependent on the preservation temperature. The increase of carbon dioxide in the lungs that were inflated with 100% nitrogen was very small. When the oxygen was not available in the alveoli, lactate accumulated, and adenosine triphosphate and phosphocreatine decreased in the lung tissue. We concluded that lung cells are able to maintain aerobic metabolism with the oxygen in the alveoli during preservation and that the maintenance of aerobic metabolism may be essential to maintain the optimum viability of preserved lung tissue. PMID- 8445928 TI - Exclusion of the placenta during fetal cardiac bypass augments systemic flow and provides important information about the mechanism of placental injury. AB - The in utero correction of congenital cardiac malformations requires the availability of fetal cardiac bypass. One difficulty with fetal cardiac bypass is that very high flow rates are necessary when the placenta is left in the bypass circuit; the placenta requires about 40% of fetal cardiac output, which results in a normal cardiac output of 400 ml/kg per minute. Previous attempts to perform fetal cardiac bypass failed to consistently achieve these high flow rates because of cannula size limitations. On the basis of previous work done in our laboratory with an isolated-placenta model, which demonstrated that at normothermia the placenta would tolerate at least 30 minutes of cessation of umbilical blood flow, we hypothesized that exclusion of the placenta from the fetal cardiac bypass circuit would reduce fetal cardiac output by one half and allow us to obtain better systemic perfusion without compromising placental function. Cardiac bypass was performed in 20 late-gestation fetal lambs. In 10 lambs, no drugs were given; 5 served as controls in which the placenta was perfused; in the last 5, the placenta was excluded by clamping the umbilical cord during bypass. The latter 10 lambs were treated with indomethacin, which is known to improve placental blood flow after fetal cardiac bypass. We measured blood gases and determined regional blood flow with radiolabeled microspheres to assess placental function after bypass. The 5 control fetuses experienced rapid hypercapnea and hypoxemia after bypass, in association with minimal placental blood flow; when the placenta was excluded, arterial carbon dioxide tension rose somewhat more slowly, and placental blood flow after bypass was significantly better. When indomethacin was given, arterial blood gases in both groups showed a mild increase in carbon dioxide tension and similar placental blood flows (about 30% of baseline) after bypass. Indomethacin is known to block the vasoconstrictive response of the placenta to fetal cardiac bypass, implicating the release of vasoactive cyclooxygenase products as the cause of the adverse effects. In this study, placental perfusion on bypass without indomethacin caused much more severe placental dysfunction than did bypass with the placenta excluded from the circuit. The use of indomethacin improved postbypass placental function in both groups, but this effect was much more dramatic in the placenta-perfused group.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8445929 TI - A long-term ventricular assist system. AB - An implantable, electrically powered pump that will provide tether-free circulatory support is being developed. The blood pump consists of a seamless polyurethane sac within a polysulfone case. Bjork-Shiley Monostrut valves provide unidirectional flow. The blood sac is compressed by a pusher plate with a stroke of 1.9 cm and actuated by a brushless direct-current electric motor and motion translator. The current unit is completely sealed, and inductive coupling techniques provide the electrical energy. The system has an implantable electronic control system as well as a battery that provides 30 minutes of operation when the external coil is disconnected. During normal operation, however, the pump is powered by a portable battery pack or by house current. The unit can pump 8.5 L/min at physiologic pressures. Twenty-six animals have had circulatory support for a period of more than 1 week. The average period of pumping was 62 days; the longest was nearly 8 months. Experiments were terminated in 18 animals because of pump-related problems and in 8 because of biologically related problems. Studies to date are very encouraging and suggest that, with further refinement, a reliable 2-year assist pump that will have important clinical application can be developed. PMID- 8445930 TI - The protective effect of magnesium on acute catecholamine cardiotoxicity in the neonate. AB - Neonates undergoing heart surgery are exposed to high levels of circulating catecholamines. Our objective was to determine to what extent administration of magnesium counters epinephrine-induced cardiotoxicity. We assessed left ventricular function (pressure-volume data obtained by the conductance catheter/micromanometer technique) and ultrastructure in newborn pigs 3 to 5 days of age before and after administration of epinephrine alone (2 micrograms/kg/min, group A, n = 6) and simultaneously with magnesium sulfate (8 mmol/L, 5 ml/hr, group B, n = 6). Plasma levels of magnesium were maintained at 200% to 250% of control, and ionized calcium was maintained at normal levels. During administration of epinephrine, there was a significant increase in end-systolic elastance from 8.9 +/- 2 to 15 +/- 3 mm Hg/ml in group A and from 7.8 +/- 2 to 16 +/- 3 mm Hg/ml in group B (p < 0.05). This increase was accompanied by an increase in chamber stiffness index (p < 0.05) and shortening of the time constant of isovolumic relaxation (p < 0.05; group A, 19 +/- 3 to 13 +/- 3 msec; Group B, 20 +/- 2 to 15 +/- 2 msec). After epinephrine was discontinued, however, systolic and diastolic indexes returned to baseline levels in group B, whereas group A exhibited a significant reduction in end-systolic elastance (5 +/- 1 mm Hg/ml; p < 0.05) and an increase in chamber stiffness index (0.7 +/- 0.08 versus 0.4 +/- 0.1 ml-1; p < 0.05) and time constant (25 +/- 1 versus 19 +/- 3 msec). Left ventricular dysfunction in group A was associated with focal sarcolemmal rupture and mitochondrial swelling, whereas only minor reversible changes (microvesicular lipid accumulation) were seen in group B. We conclude that magnesium has a protective effect against epinephrine-induced cardiotoxicity because of its blocking action on calcium influx of ionized calcium and could be of therapeutic benefit in the perioperative period. PMID- 8445931 TI - Effects of 2,3-butanedione monoxime in isolated hearts: protection during reperfusion after global ischemia. AB - The cardiac effects of 2,3-butanedione monoxime on electrical and mechanical function, rhythm, oxygen utilization, and coronary flow responsiveness, particularly during severe ischemia and reperfusion, have not been studied. After perfusing hearts at 55 mm Hg, coronary perfusion was interrupted for 30 minutes and was then reestablished at the control perfusion pressure for 40 minutes. Hearts were divided into four groups (n = 10 each) treated with 0, 3, 5, or 10 mmol/L of 2,3-butanedione monoxime added to the perfusate for 10 minutes before and during ischemia and for the first 10 minutes of reperfusion. An additional nonischemic group served as a time control. Variables monitored were heart rate, atrioventricular conduction time, cardiac rhythm, isovolumetric systolic and diastolic left ventricular pressure, maximum rate of left ventricular pressure change, coronary flow, myocardial oxygen consumption, and the ratio of oxygen delivery to myocardial oxygen consumption. Before ischemia, 2,3-butanedione monoxime significantly decreased isovolumetric left ventricular systolic pressure and increased the ratio of oxygen delivery to myocardial oxygen consumption in a dose-dependent manner, with only slight changes in heart rate and atrioventricular time with 10 mmol/L of 2,3-butanedione, monoxime. After 40 minutes of reperfusion, isovolumetric left ventricular systolic pressure recovered to 81 +/- 5% and 83 +/- 2% of the initial control values for the 5 and 10 mmol/L 2,3-butanedione monoxime groups. This was significantly greater than the recovery for the 0 and 3 mmol/L 2,3-butanedione monoxime groups, 59 +/- 3% and 63 +/- 4%, respectively. Similarly, the duration of ventricular fibrillation and of tachycardia was significantly lower, coronary flow reserve was better preserved, and myocardial oxygen consumption was greater with reperfusion in the 5 and 10 mmol/L 2,3-butanedione monoxime groups than in the 0 mmol/L 2,3 butanedione monoxime group. This study shows that relatively low concentrations of 2,3-butanedione monoxime, given before global ischemia and early during reperfusion of isolated hearts, can protect against dysrhythmias and improve return of myocardial and vascular function. PMID- 8445932 TI - Flavone improves functional recovery after ischemia in isolated reperfused rabbit hearts. AB - The effects of flavone (2-phenyl-1,4-benzopyrone), a modulator of the cytochrome P-450 monooxygenase system, on myocardial postischemic reperfusion recovery were examined in the present study. Left ventricular functional recovery was evaluated in isolated, crystalloid-perfused rabbit hearts after 2 hours of modestly hypothermic (34 degrees C) global ischemia. Four groups (n = 8 in each group) were studied and compared: a vehicle control group, a second group pretreated with flavone (8 x 10(-6) mol/L) before ischemia, a third group pretreated with flavone followed by SKF 525-A (1.7 x 10(-5) mol/L), an inhibitor of cytochrome P 450, and a fourth group pretreated with flavone followed by indomethacin (1 x 10( 6) mol/L), an inhibitor of cyclooxygenase. At 15, 30, and 45 minutes after reperfusion, recovery of left ventricular developed pressure in the control group averaged (mean +/- standard deviation) only 2.60% +/- 12.7%, 35.5% +/- 15.0%, and 42.9% +/- 13.5% of baseline, respectively. In the flavone-treated group, recovery was significantly better, averaging 67.7% +/- 10.7%, 73.9% +/- 9.3%, and 73.6% +/ 7.6% of baseline at the same time periods. Recovery of peak positive rate of pressure rise in the control group averaged 27.4% +/- 15.2%, 38.6% +/- 19.2%, and 45.4% +/- 18.6% of baseline at 15, 30, and 45 minutes of reperfusion, respectively. In the flavone-treated group recovery values were significantly higher, averaging 67.8% +/- 9.6%, 77.3% +/- 8.5%, and 77.0% +/- 9.0% of baseline. End-diastolic pressures were significantly lower in the flavone-treated group compared with the control group at all reperfusion time points. Myocardial oxygen consumption was significantly higher in the flavone-treated group at 30 and 45 minutes of reperfusion, as well. The improvement resulting from flavone infusion was abolished completely by SKF 525-A, providing support for the interpretation that the effects of flavone were mediated through the cytochrome P-450 system. The cyclooxygenase inhibitor indomethacin midly attenuated the effects of flavone pretreatment, suggesting that the effects of flavone were only minimally related to metabolites of cyclooxygenase. We conclude that pretreatment with flavone represents a promising approach to myocardial protection that may be due to modulation of the myocardial cytochrome P-450 system. PMID- 8445933 TI - Intraoperative use of inhaled low-dose nitric oxide. PMID- 8445934 TI - Proton gradient during cardiac arrest: oxygenation of St. Thomas' Hospital cardioplegic solution and carbon dioxide level. PMID- 8445935 TI - Invited letter concerning: Technique for prevention of gastroesophageal reflux after transthoracic Heller's operation. PMID- 8445936 TI - Cold agglutinins and warm heart surgery. PMID- 8445937 TI - Thoracic wall necrosis in a patient with internal mammary-coronary bypass after prosthetic replacement of the thoracoabdominal aorta. PMID- 8445938 TI - Plasma levels of endothelin-1 and thrombin-antithrombin III complex in patients undergoing open chest operations. PMID- 8445939 TI - A simple and versatile sling sternal retractor for internal mammary artery harvesting. PMID- 8445940 TI - Intrathoracic meningocele. PMID- 8445941 TI - An infectious etiology for common acute lymphoblastic leukemia in childhood? AB - Childhood leukemia is a biologically and clinically diverse disease and is likely to arise via a number of etiological pathways. The common, B-cell precursor, form of acute lymphoblastic leukemia (cALL) accounts for the peak of childhood leukemia at 2-5 years of age. Recent epidemiological data, reviewed here, indicate that risk of cALL is increased by higher socio-economic status, isolation, and other community characteristics suggestive of abnormal patterns of infection during infancy. These data are compatible with the emerging concept that cALL may be a rare response to common infection(s). PMID- 8445942 TI - Granulocyte-macrophage colony-stimulating factor in association to timed sequential chemotherapy with mitoxantrone, etoposide, and cytarabine for refractory acute myelogenous leukemia. AB - Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF), given intravenously 5 micrograms/kg per day, was administered on days 4-8 of timed-sequential chemotherapy (TSC) with mitoxantrone, 12 mg/m2 per day on days 1 3, etoposide, 200 mg/m2 per day on days 8-10 and cytarabine, 500 mg/m2 per day on days 1-3 and 8-10, in 22 patients aged < 60 years with refractory acute myelogenous leukemia in an attempt to increase recruitment of leukemic cells in S phase before the second sequence of TSC. Thirty-eight patients treated with TSC without GM-CSF in a previous trial served as historical controls. In GM-CSF treated patients, median duration of neutropenia < 0.5 x 10(9)/1 was 33 days and of platelet transfusion requirement 30 days, without any increase by comparison with controls. WHO grade 3 or more extra-hematologic toxicity included sepsis in 60% of patients, vomiting in 30%, diarrhea in 15%, hyper-bilirubinemia in 15%, and mucositis in 10%, without any difference with controls. Among 20 evaluable patients six individuals (30%), with a 95% confidence interval (CI) ranging from 12-54% achieved complete remission, 11 (55%, CI 31-77%) did not respond to therapy and three (15%, CI 3-38%) died from infection. There was no demonstrable in vivo proliferation of leukemic cells during the 5 days of administration of GM CSF. The average percentage of bone marrow cells in S phase in five patients was 4.0 +/- 2.8 on day 4 and 7.0 +/- 7.2 on day 8 (p = NS). In this cohort of patients refractory to cytarabine, addition of GM-CSF did not increase efficacy of TSC by comparison with historical controls. PMID- 8445943 TI - Neurotoxicity associated with fludarabine and cytosine arabinoside chemotherapy for acute leukemia and myelodysplasia. AB - Neurological toxicity occurred in 8/219 patients treated with fludarabine (FAMP), 30 mg/m2 per day and cytosine arabinoside (Ara-C), 0.5 g/m2 per hour for 2-6 hours for 5 days, for new or relapsed acute leukemia or myelodysplasia. Two patients developed severe, progressive cerebral dysfunction that was ultimately fatal. This toxicity was similar to that seen with high-dose fludarabine therapy and was limited to patients with serum creatine > or = 2.0 mg/dl and age over 60 years, occurring in 2/9 such patients compared to 0/210 among the other patients (p < 0.005). Since FAMP is partially excreted by the kidney, toxicity in these two patients was likely due to receiving an effectively high dose of FAMP. Five patients developed peripheral neuropathy but there was no association with age, creatinine, dose of Ara-C, or number of courses. A patient, who also received intrathecal Ara-C, developed myelopathy. At this dose rate and duration of Ara-C peripheral neuropathy rarely arises, and cerebral toxicity is not seen. Neither toxicity was observed in 481 chronic lymphocytic leukemia patients treated with FAMP alone, by the same dose and schedule, suggesting that combination with Ara-C is important for the development of at least the peripheral neuropathy. The incidence of neurotoxicity with FAMP/Ara-C is low especially in comparison with high-dose Ara-C therapy (3 g/m2 over 2 hours). Cerebral toxicity can likely be decreased by dose reduction of FAMP in patients with increased creatinine and peripheral neuropathy decreased by detailed neurological examination before courses of FAMP/Ara-C. PMID- 8445944 TI - Interphase cytogenetics by fluorescent in situ hybridization (FISH) for characterization of monosomy-7-associated myeloid disorders. AB - By circumventing the need for metaphase preparations, fluorescent in situ hybridization (FISH) on interphase nuclei using chromosome-specific probes is a promising tool for the study of numerical chromosome aberrations not only in proliferating, but also in non-dividing cells. We analyzed 15 cases of monosomy-7 associated myeloid disorders with a biotinylated probe to the (peri)centromeric region of chromosome 7. Monosomy 7 was readily confirmed in all cases during active disease. In two patients only a minority of nuclei was monosomic, whereas cytogenetics had shown all metaphases to be missing one chromosome 7. FISH in one of them was able to identify a small marker chromosome as isolated pericentromeric region of chromosome 7. Minimal residual disease however could not be detected in three remission samples analyzed, as percentages of disomic nuclei were within the range of normal controls (96.8% 2.1%). In order to determine lineage involvement of the monosomic clone, a recent technique combining immunophenotyping and FISH (FICTION) was performed in one patient with AML after MPD. Monosomy 7 was found in virtually all myelomonocytic and erythroid cells (as discriminated by lineage-specific antibodies), in a part of CD34 positive precursor cells, but not in lymphocytes. We conclude that monosomy 7 in this patient is restricted to an early committed progenitor cell capable of erythroid and myelomonocytic differentiation. PMID- 8445945 TI - Cellular drug resistance profiles that might explain the prognostic value of immunophenotype and age in childhood acute lymphoblastic leukemia. AB - Immunophenotype and age have prognostic value in childhood acute lymphoblastic leukemia (ALL) but how this operates is not understood. In 84 children with ALL at initial diagnosis we studied the correlation between these factors and the in vitro resistance to eight drugs, determined with the 3-(4,5-dimethylthiazol-2-yl 2, 5-diphenyl tetrazolium bromide (MTT) assay. B-lineage ALL samples were classified into four differentiation stages: the CD10- proB ALL; cALL; preB ALL with cytoplasmic mu positive ALL cells; and B-ALL with surface immunoglobulin positive (Ig+) cells. cALL and preB ALL cases have the best prognosis; proB and T ALL cases show a worse prognosis and B-ALL the poorest prognosis. Patients aged < 18 months and > 10 years have a poor prognosis compared to patients in the intermediate age group. Our results show that cALL and preB ALL cells were the most drug-sensitive cells compared to the other phenotypes. No differences were found between cALL and preB ALL cases with the exception that preB cells were more sensitive to mustine and mafosfamide (Maf). Compared to cALL and preB ALL cases, T-ALL cases were significantly more resistant to prednisolone (Pred), daunorubicin (DNR), L-asparaginase (L-Asp), cytosine arabinoside (AraC), and Maf; proB ALL cases were more resistant to Pred, DNR, L-Asp, and 6-thioguanine. The three B-ALL cases were resistant to vincristine and DNR. Two out of three B-ALL were resistant to Pred. Compared to cells from patients aged 18 months to 10 years, cells from children < 18 months were more resistant to Pred and DNR; cells from children > 10 years were more resistant to Pred. We conclude that cellular drug-resistance patterns might at least partly explain the prognostic value of immunophenotype and age in childhood ALL. PMID- 8445946 TI - Cytokine modulation of the susceptibility of acute T-lymphoblastic leukemia cell lines to LAK activity. AB - We studied the regulatory effects of various cytokines on the susceptibility to lymphocyte-mediated lysis of cell lines established from patients with acute T lymphoblastic leukemia (T-ALL). None of the cytokines tested affected the sensitivity of these targets to natural killer activity. In contrast, specific cytokines, different for each cell line, enhanced the susceptibility to lymphokine-activated killer (LAK) cells, while interferon gamma (IFN)-gamma always induced resistance. The same cytokines that increased LAK susceptibility also induced proliferative responses. The TALL-101 cell line, which responded to granulocyte-macrophage colony-stimulating factor (GM-CSF) with increased susceptibility to lysis, and to IFN-gamma with resistance, was used as a model to analyze the mechanisms underlying these changes. Cold target inhibition and conjugate formation assays both indicated that the changes in LAK susceptibility were not at the level of effector-target (E/T) binding. Furthermore, no significant changes in surface expression of adhesion molecules involved in E/T binding were induced by either GM-CSF or IFN-gamma on TALL-101 cells. Finally, N alpha-benzyloxycarbonyl-L-lysine thiobenzyl-esterase assays demonstrated no differences in the ability of these cytokines to trigger the secretion of cytolysins in the bound effectors compared to unstimulated cells. Taken together, these results suggest that the cytokine-modulated susceptibility to lysis of these T-ALL lines might occur at a post-binding stage with mechanisms involving an altered responsiveness to lytic factors. PMID- 8445947 TI - Alpha (p55) and beta (p75) chains of the interleukin-2 receptor are expressed by AML blasts. AB - In the present study, we have investigated the leukemic cells obtained from 16 patients with acute myeloid leukemia (AML) at diagnosis for the membrane expression of p55 (alpha) and p75 (beta) interleukin-2 receptor (IL-2R) chains using specific monoclonal antibodies (mAbs), as well as for the presence of their transcripts using Northern blot analysis. In addition, immunoprecipitation of the p75 membrane molecule with TU27 and Mik-beta 1 mAbs was carried out in selected cases. The p75 IL-2R beta transcripts were detected in all cases, whereas the membrane p75 molecule was demonstrable by flow cytometry in three cases. However, data from the immunoprecipitation analysis suggest that the lack of the p75 IL-2R detection by flow cytometry might be caused by the low density of molecules per cell rather than the fact that the specific mRNA is not translated into the p75 surface molecule. In addition, a consistent membrane positivity with an anti p55/CD25 mAb, present on fresh uncultured blasts in 37.5% of the cases, became detectable after short-term culture in 75% of cases. In each individual case, a strict correlation was found between membrane CD25 reactivity and the expression of p55 mRNA. Taken together, our data suggest that the expression of both alpha (p55) and beta (p75) IL-2R molecules is a common feature of leukemic cells in AML, and provide new arguments for reassessing the possible role of IL-2 in leukemic growth. PMID- 8445948 TI - Recombination activating gene-1 (RAG-1) expression in all differentiation stages of B-lineage precursor acute lymphoblastic leukemia. AB - The recombination activating gene-1 (RAG-1), which is required for immunoglobulin (Ig) gene rearrangement, is expressed in murine B-lymphoid precursors but not in mature B lymphocytes. In order to characterize the temporal relationship of RAG-1 expression to other markers of human B-lymphoid differentiation [cell surface antigens, terminal deoxynucleotidyl transferase (TdT), Ig gene rearrangements], RAG-1 expression was studied in a group of B lineage childhood acute lymphoblastic leukemia (ALL). ALL cells from 21 patients were grouped into three developmentally related phenotypes based on the expression of the differentiation antigens CD19, CD10, and CD20. All 21 leukemias were surface Ig (slg) negative. There were leukemias representing each developmental stage of Ig gene rearrangement. RAG-1 was expressed in 20 of 21 B-lineage ALL, including leukemic cells from each stage of differentiation, as defined by immunophenotype and IgH and IgL gene rearrangement status. RAG-1 was expressed in slg- ALL, regardless of the Ig heavy chain (IgH) or Ig light chain (IgL) gene configuration. RAG-1 was not expressed in two Burkitt lymphomas and Burkitt lymphoma cell lines with slg+ mature B-lymphocyte phenotype. In two cases, RAG-1 was expressed in TdT-negative ALL; conversely TdT was expressed in the one RAG-1 negative ALL. These results suggest that RAG-1 in B-lineage ALL is expressed at all phenotypic and genotypic developmental stages preceding surface immunoglobulin expression, and that TdT and RAG-1 may be regulated by different mechanisms. PMID- 8445949 TI - Increased expression of GATA-1 and NFE-2 erythroid-specific transcription factors during aclacinomycin-mediated differentiation of human erythroleukemic cells. AB - Anthracycline antitumor drugs, particularly aclacinomycin (ACM) have been shown to be potent inducers of erythroid differentiation in human leukemic K562 cells. Here we report that such an event is associated with an overexpression of the erythroid-specific transcription factors GATA-1 and NFE-2. Using the electrophoretic mobility shift assay, during differentiation over 3 days of culture, we have observed an increase in the binding either of GATA-1 to the promoter of the gamma-globin gene (region -201 to -156) or NFE-2 to the promotor of the porphobilinogen deaminase gene (region -170 to -142). Both events were paralleled by a recruitment of hemoglobinized cells and a stimulation of heme synthesis. Enhanced binding capacity of GATA-1 was confirmed by an increase in its mRNAs. Moreover, GATA-1 and NFE-2 overexpression has been shown to be specific of the differentiating effect of the drug and not of its growth inhibitory effect. In contrast, no change was observed in the binding of the ubiquitous factors OTF-1 and AP-1, except on day 3, where AP-1 decreased. Although ACM is a DNA-intercalating agent, it did not directly affect transcription factors binding to their cis-sequences as assessed by the preincubation of the oligonucleotides probes with increasing concentrations of ACM. Taken together, these results strongly suggest that ACM could exert their erythroid-differentiating activity by modulating the expression of transcription factors which specifically regulate the transcription of erythroid genes. PMID- 8445950 TI - All-trans retinoic acid induces monocyte growth factor receptor (c-fms) gene expression in HL-60 leukemia cells. AB - All-trans-retinoic (ATRA) treatment of patients with acute promyelocytic leukemia results in differentiation of the malignant cells and a high complete remission rate. ATRA treatment induced granulocytic differentiation in HL-60 cells as assessed by nitroblue tetrazolium (NBT) reduction, but had no effect on non specific esterase (NSE) straining, as expected in cells maturing along the monocytic lineage. However, our results demonstrate that ATRA (0.1-10 microM) induces expression of the c-fms (monocyte colony-stimulating factor receptor) gene in HL-60 cells. This effect was detectable after 2 days and expression was maximal at 5 days. Similar results were obtained during treatment with cis retinoic acid (CRA), hexamethylene bisacetamide (HMBA), or dimethyl sulfoxide (DMSO). The results also demonstrate that ATRA-induced c-fms expression is potentiated by exposure to tumor necrosis factor alpha (TNF alpha) or dibutyryl cyclic adenosine monophosphate (cAMP). The induction of c-fms transcripts by ATRA is associated with induction of M-CSF-binding ability, suggesting cell surface expression of the monocyte growth factor receptor. Our results indicate that retinoic acid can induce features of both monocytic and granulocytic differentiation in HL-60 cells. PMID- 8445951 TI - Response of therapy-related myelodysplasia to low-dose interleukin-2. AB - We report the case of a patient treated with interleukin-2 (IL-2) for refractory anemia with excess blasts (RAEB), which developed during third complete remission of acute lymphoblastic leukemia. IL-2 was given subcutaneously at 2.5 x 10(5) IU (= 10(5) BRMP units) twice daily for 30 days. During treatment spontaneous natural killer (NK) activity was enhanced, circulating lymphokine-activated killer effector cells became detectable and CD56+/CD3- NK cells in the blood doubled. The response in the bone marrow was a reduction in myeloid blast cells (from 7 to 0%), ringed sideroblasts (from > 15 to 0%) and dysplasia (from trilineage to minimal megakaryocytic), and a decrease in metaphases with the RAEB karyotype (from 43 to 2%). Toxicity of IL-2 was minimal. Thus a relatively low dose of IL-2 caused immune activation and resulted in significant hematologic and cytogenetic response in this case of therapy-related myelodysplasia. PMID- 8445952 TI - Demyelinating neuropathy and acute lymphocytic leukemia. AB - We report a 67-year-old man with acute lymphocytic leukemia (ALL) who developed a rapidly progressive areflexic quadriparesis following chemotherapy. Electrophysiologic studies demonstrated an acute demyelinating polyneuropathy. Although peripheral nervous system dysfunction in ALL is often attributed to leukemic infiltration or chemotherapy, a diligent search with electrophysiologic evaluation should be considered and may suggest alternative diagnoses. PMID- 8445953 TI - Amplification of c-MYC oncogene and point mutation of N-RAS oncogene point mutation in acute myelocytic leukemias with double minute chromosomes. AB - Two patients with acute myelocytic leukemia (AML) showing double minute (dmin) chromosomes were analysed to identify oncogene activation. Cytogenetic analysis showed 1-53 dmin chromosomes with the normal karyotype in the first patient and 1 84 dmin chromosomes with complex chromosome aberrations. Analysis of DNA from two patients revealed five- to tenfold amplification of c-MYC oncogene in the leukemic cells. The other sixteen oncogenes studied showed no increase in the gene content. Furthermore, a transforming gene, N-RAS was detected in the first patient by nude mouse tumorigenicity assay (in vivo selection assay). These results suggest that the amplification of c-MYC gene is common in dmin-positive AML patients and co-ordination of c-MYC and N-RAS oncogene might also play a significant role in the pathogenesis of some AML patients. PMID- 8445954 TI - Drugs controlling triglyceride metabolism. PMID- 8445955 TI - New approaches to atherosclerosis: an overview. AB - The mechanisms of action and selected agents for a variety of approaches to the treatment of atherosclerosis have been reviewed. In Table I, each approach is listed according to its primary physiological effect. This is a simplification, of course, and some agents, such as ACAT inhibitors, may have primary effects in all of these categories. As one goes from left to right, the benefit of each physiological effect becomes more speculative. There is no question of the benefit of LDL reduction, but less evidence exists for the clinical benefits of HDL elevation. With regard to direct anti-atherosclerotic effects, most approaches have yet to gather clinical data of any type. Perhaps as a result, the degree of medicinal chemistry effort in each area to date declines as one goes from left to right. This situation is changing rapidly, however. As evidence supporting the HDL hypothesis accumulates and knowledge of how to elevate HDL levels grows, very exciting opportunities for medical advances present themselves. Likewise, the knowledge base for nonlipid intervention is growing and very rapid advances are being achieved with the plaque-imaging techniques needed for evaluating such agents in man. Such results can only lead to greater opportunities for pharmacological intervention. Thus, in the future, much greater research effort will likely be dedicated to HDL elevation and nonlipid approaches. Through these efforts, physicians of the future should be armed with several complementary agents that can reduce the risk of cardiovascular disease in all patient populations. PMID- 8445956 TI - Antioxidants: a biological defense mechanism for the prevention of atherosclerosis. PMID- 8445957 TI - Antimitotic agents: chemistry and recognition of tubulin molecule. PMID- 8445959 TI - [University hospital and the "tree of knowledge." Physicians are not some unique academicians]. PMID- 8445958 TI - Pepstatins: aspartic proteinase inhibitors having potential therapeutic applications. PMID- 8445960 TI - [The "orienteering disease"--more cases discovered. A new type of myocarditis behind sudden death?]. PMID- 8445961 TI - [Pediatric surgeons misunderstood]. PMID- 8445962 TI - [Supposedly comforting information about passive smoking]. PMID- 8445963 TI - [Cerebral paresis in full term infants. Could it be prevented?]. PMID- 8445964 TI - [How small is too small?]. PMID- 8445965 TI - [Infantile hydrocephalus. Complication of prematurity]. PMID- 8445966 TI - [Vascular surgery in ischemia of the extremities. Have the therapeutic results changed for the worse?]. PMID- 8445967 TI - [Post-traumatic stress. Extreme loads are followed by conditions which should be known by all clinically active physicians]. PMID- 8445968 TI - [Discovery after botulinum poisoning: shops store smoked fish too long in too high temperatures]. PMID- 8445970 TI - [The debate on grades--a skeleton in the closet]. PMID- 8445969 TI - [Diagnostic delay in breast cancer. Causes and significance for prognosis]. PMID- 8445971 TI - [Choosing among students who passed all tests...]. PMID- 8445972 TI - [Endosonography in tumors of the pancreas and bile ducts]. AB - The sensitivity of EUS in demonstrating pancreatic tumors lies above 90% and tumors smaller than 2 cm in diameter can be visualized. Therefore EUS can be applied e.g. in the early diagnosis of symptomatic endocrine tumors. However, it is not suited as a screening method for pancreatic carcinoma in asymptomatic patients. The EUS findings do not permit a clear differentiation between malignant and inflammatory (pseudo) tumors. The specificity for the demonstration of malignant tumors is 74%. Its main importance is in the locoregional staging of tumors. EUS is superior to all other imaging tools in determining tumor extension and infiltration into the portal or splenic vein. The pT-stage is determined correctly preoperatively in 90% and lymph node metastases (N1) in about 73% (sensitivity 80-90%/specificity 50%) of the cases. Malignant tumors of Vater's papilla (ampullary tumors) and of extrahepatic bile ducts can be demonstrated endosonographically in nearly all cases. However, tumors of the proximal bile ducts, especially of the right hepatic duct are difficult and sometimes impossible to visualize. The value of EUS in bile duct cancer is in local tumor staging. The pT-stage is determined correctly in 80-90%, the sensitivity and specificity for N1-stage is 80-90% and 30% respectively. Comparative studies with other methods are lacking at the present time. The value of EUS in gall bladder tumors is not yet determined. Stones in the gall bladder may hinder the visualization of the gall bladder wall. In one study the pT-stage for gall bladder carcinoma was determined correctly preoperatively in 76.9% and the N1 stage in 80.7% of cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8445973 TI - [Structured documentation of findings and user acceptance--results of a study of abdominal ultrasound]. AB - Structured reporting of medical findings is known to have positive effects on data quality, whereas user acceptance tends to be low because of time requirements. This paper presents the results of a survey among 19 physicians who worked for 14 months with a computer system using structured data input for abdominal ultrasonography. During this time, they prepared 8.827 reports. The two most important results are that it is feasible to realize well accepted documentation systems with high data quality by using modern computer technology, and that graphic user interfaces tend to increase user acceptance. For comparable systems, evaluation studies are suggested. PMID- 8445974 TI - [Differential determination of fibrinogen degradation products in assessment of the stages of plasma consumption in patients with infection and liver cirrhosis]. AB - In the present study soluble fibrin complexes and fibrin(ogen) degradation products are determined in patients with sepsis and liver-cirrhotic simultaneously by means of FM-Test, FDP-Kit and SCT in order to detect the different and early phases of disseminated intravascular coagulation. According to the possible configuration of test results 43 patients (sepsis n = 23, liver cirrhotic n = 20) could be grouped in 4 phases. The FDP-concentrations and the FM Test-result appear to be independent from one another. A positive FM-Test was found at least once in 35% of patients with liver-cirrhotic and 26% of patients with sepsis. The correlation coefficient for the two FDP-Tests (FDP-Kit and SCT) was r = 0.97 (p < 0.001) for liver-cirrhotic and r = 0.98 (p < 0.001) for sepsis. PMID- 8445975 TI - [Idiopathic ulcer of the small intestine]. AB - The authors report on a female patient, 32 years old, suffering for eight years from recurrent and progressive abdominal pain, combined with chronic anemia, due to iron deficiency. Neither anamnesis and clinical course, nor technical examinations elucidated the etiology. Finally an explorative laparotomy with segmental resection of the small intestine led to diagnosis and healing of the rare "idiopathic small bowel ulcer". Possible differential diagnoses were lacking. This case report demonstrates the need of an invasive and aggressive diagnostic approach after excluding all common causes of disease, related to the symptoms, in order to prevent patients from suffering for years. PMID- 8445976 TI - [Computer support in the gastroenterology unit]. PMID- 8445977 TI - Inhibition of heme oxygenase after oral vs intraperitoneal administration of chromium porphyrins. AB - The effects of chromium porphyrins on suckling rat heme oxygenase activity were compared following oral vs intraperitoneal dosing. Chromium protoporphyrin (CrPP), chromium mesoporphyrin (CrMP), or chromium deuteroporphyrin 2,4 bis glycol (CrBG) were administered at 40 mumol/kg to 2-week old suckling rats either orally or intraperitoneally. Six hours after intraperitoneal dosing, CrPP and CrMP had significantly reduced hepatic and splenic heme oxygenase activity by more than 55%. CrBG effectively reduced hepatic heme oxygenase activity by 42%. More importantly, only CrMP was an effective inhibitor of hepatic heme oxygenase activity 6 hr after oral administration. In the first reported comparison of chromium porphyrin efficacy in vivo, our data suggest that chromium porphyrins, and particularly CrMP, may be effective in chemopreventive strategies for the treatment of neonatal jaundice. PMID- 8445978 TI - In rats, the metabotropic glutamate receptor-triggered hippocampal neuronal damage is strain-dependent. AB - The effect of intrahippocampal (i.h.) and intraocular (i.o.) administration of the selective metabotropic glutamate receptor (mGluR) agonist (1S,3R)-1 aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) was studied in different rat strains. A massive hippocampal damage was observed in CD/SD and Fischer 344 but not in SD/Rij and Brown Norway rats 7 days following the i.h. injection of 1S,3R ACPD, while no retinal damage was observed following its i.o. administration. Moreover, 1S,3R-ACPD reduced the N-methyl-D-aspartate (NMDA) toxicity in the retina of both CD/SD and SD/Rij rats. Regardless of its toxic action on hippocampal neurons the i.h. injection of 1S,3R-ACPD caused an acute stimulation of motor activity in both CD/SD and SD/Rij rats. This effect was blocked by the intracerebroventricular (i.c.v.) administration of the putative mGluR antagonist L-2-amino-3-phosphono-propionic acid (L-AP3). It is suggested that the differential expression of mGluR subtypes might determine their role in brain pathology. PMID- 8445979 TI - Amiodarone N-deethylation in human liver microsomes: involvement of cytochrome P450 3A enzymes (first report). AB - Experiments were conducted on three different human liver samples to identify the cytochrome P450 isozyme which is involved in the biotransformation of the class III antiarrhythmic agent, amiodarone, into its major metabolite, desethylamiodarone (DEA). The classic P450 inhibitors, SKF 525A, metyrapone, and carbon monoxide provided a significant reduction in the in vitro formation of DEA by human hepatic microsomes. Amiodarone N-deethylase activities expressed by intrinsic clearance values were similar in all the livers used, although two livers were genotyped as extensive and one as a poor metabolizer for the cytochrome P450 CYP2D6 gene. DEA production was strongly inhibited (more than 80%) by the anti-P450 3A4 antibody, but not by anti-LKM1-positive serum. It seems therefore that the P450 3A subfamily is certainly implicated in human hepatic amiodarone N-deethylation. PMID- 8445980 TI - New glucagon analogues with conformational restrictions and altered amphiphilicity: effects on binding, adenylate cyclase and glycogenolytic activities. AB - In an effort to obtain highly potent glucagon antagonists, we have investigated glucagon (1) structure-function relationships utilizing the following design principles: (1) structural changes known to lead to partial agonist activities; (2) conformational restrictions; (3) changes in the conformational probabilities of the primary sequence; and (4) increased amphiphilicity. In this report we present the total synthesis, purification, receptor binding, adenylate cyclase activity, in vivo glycogenolytic activity and CD spectrum of the following four glucagon analogues: [Ahx17,18]glucagon (2), [D-Phe4,Tyr5, 3,5-diiodo Tyr10,Arg12,Lys17,18,Glu21]glucagon (3), [Asp9,Lys12,Lys17,18,Glu21]glucagon 4, and [Glu15,Lys17,18]glucagon 5. Compound 2 binds exclusively to the high affinity receptor and compound 3 was a highly potent antagonist with respect to adenylate cyclase activity. Analog 4 showed distinct biphasic binding (IC50 5.6 nM and 630 nM), with only the low affinity binding leading to adenylate cyclase activity. Furthermore in analogue 5 receptor binding and adenylate cyclase activity were dissociated by a factor of 5. The results are consistent with a multistep binding mechanism in which glucagon interacts first nonspecifically with the anisotropic interphase of the cell membrane, followed by a conformational transition which occurs in the sequences 10-14 and 15-18 when the membrane bound peptide binds to its receptor. PMID- 8445981 TI - Transient blocking of persistent gnawing by haloperidol in rats with seizure induced multifocal brain damage. AB - Frequent but phasic gnawing of objects is displayed by rats in which severe damage within: 1) the substantia nigra reticulata, 2) all of the amygdaloid nuclei except the central group and 3) multiple thalamic nuclei, was induced by lithium/pilocarpine-induced seizures. Multiple lesions were produced by these rats upon their own tails as well as upon the tails of their cage mates. These behaviors were considered predictable sequela of the disinhibition of compacta dopamine upon orofacial mechanisms that are modulated by the corpus striatum. In a manner similar to tail pinch-induced eating, the usually quick onset of spontaneous gnawing upon food chunks in a test setting was delayed transiently by appropriate dosages of haloperidol. PMID- 8445982 TI - Proteolytic activity is altered in brain tissue of rats upon chronic exposure to ozone. AB - Tissue from pons medulla of rats exposed in vivo to various levels of ozone was assayed for calpain and cathepsin D activity. Chronic exposure to ozone increased calpain activity, which was 35% to 46% higher in the homogenates of animals exposed to 1.0 ppm ozone than in those of animals exposed to 0.5 ppm ozone or of controls. An increase in activity of 26% was also observed in the soluble supernatant. The increase in activity did not seem to be caused by ozone effects on calpastatin. Addition of 32 mM carnitine to the incubation mixture increased total activity 3-4 fold, making the differences in activity proportionately smaller. Cathepsin D activity was little altered. Changes in calpain activity and in the generation of free oxygen radicals have been implicated in the aging process, long-term exposure to ozone may magnify changes. Ozone exposure may cause changes in brain protein metabolism. PMID- 8445983 TI - Effect of caffeine treatment on plasma renin activity and angiotensin I concentrations in rats on a low sodium diet. AB - Animals treated acutely with an adenosine receptor antagonist have elevated plasma renin activity. This observation suggests that endogenous adenosine plays a physiologically significant role in restraining renin release. However, it is unclear whether chronic blockade of adenosine receptors would cause a rise of renin activity since tolerance to adenosine blockade is known to develop quickly. An earlier study partially addressed this question by showing that chronic blockade of adenosine receptors with caffeine exacerbated both the rise of plasma renin activity and the decline of renal function in 2-kidney-1-clip (2K1C) renovascular hypertensive rats. However, that study did not determine whether the difference in renin activity occurred solely as a secondary result of the difference in renal function. The purpose of this study was to reexamine the effect of chronic caffeine consumption on plasma renin activity and angiotensin I levels in animals in another high-renin model, i.e., the low sodium diet. The low sodium diet is devoid of the potential confounding effect of deteriorating renal function associated with the 2K1C renovascular hypertension model. In this study, animals received normal rat chow and drank either 0.1% caffeine water or vehicle for ten days. After ten days, all rats were switched to a low sodium diet for three weeks. Plasma renin activity and plasma angiotensin I levels were measured before, and at 1 and 3 weeks after initiating the low sodium diet. The results of this study show that chronic blockade of adenosine receptors with 0.1% caffeine water increases plasma renin activity and angiotensin I concentration before and throughout the three weeks when animals were on the low sodium diet. The results of this study suggest that the inhibitory role of adenosine on renin release is a general physiological process, rather than a special situation applicable only to the 2K1C model. PMID- 8445984 TI - (D-Ala, D-Leu) enkephalin reduces the binding of GTP in hippocampal membranes. AB - The effect of (D-Ala, D-Leu) enkephalin (DADLE) on the binding of GTP in hippocampal preparations was studied. It was observed that treatment of hippocampal slices with 10(-5) -5 x 10(-5) M DADLE followed by the preparation of membrane fractions reduced the binding of 35S-GTP-gamma-S. There was no change in the affinity of the binding. This decrease of 35S-GTP-gamma-S binding was reversed when 5 x 10(-5) M naltrindole was included. The effect was not observed when the membrane fractions were incubated with DADLE. Photoaffinity labeling with the use of 32P P3-(4-azidoanilido)-P1 5'-GTP followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography revealed the incorporation of radioactivity into molecular mass of the 43 kDa and 33-34 kDa proteins. 32P Photolabeling of both the 43 kDa and 33-34 kDa bands decreased following treatment of hippocampal slices with 10(-4) M DADLE. These results suggested that DADLE reduces the GDP-GTP exchange in hippocampal membranes. PMID- 8445985 TI - Large changes in serum free tryptophan levels do not alter brain tryptophan levels: studies in streptozotocin-diabetic rats. AB - The effect of meal-induced changes in serum free tryptophan (TRP) levels on brain TRP levels was examined in streptozotocin-diabetic rats. Diabetic rats, fasted overnight, were given free access to a non-protein food containing either no fat or large amounts of fat (45% by weight), and were killed 1, 2 or 3 hr thereafter. Ingestion of the high-fat meal produced large increases in both serum non esterified fatty acid (NEFA; 2-fold) and free TRP levels (2.5-fold), but no increments in cerebral cortical or hypothalamic TRP levels or in the rate of serotonin synthesis in these brain regions. Because the rats were diabetic, serum levels of the other large neutral amino acids (which compete with TRP for transport into brain) did not vary from fasting values in any of the treatment groups. There thus was no uncontrolled variation in the competitive transport of TRP into brain that might have obscured potential effects due to the alterations in serum free TRP levels. The results add further evidence to the notion that TRP transport into the central nervous system is not influenced by the size of the free TRP pool in blood. PMID- 8445986 TI - High-level expression in male germ cells of murine P68 RNA helicase mRNA. AB - The complete cDNA coding for mouse P68 RNA helicase was cloned and its nucleotide sequence was determined. The sequence is about 95% identical to the human equivalent. Whereas the 5'-untranslated region is less conserved (71%), the 3' ends of mouse and human mRNAs are nearly identical. Between stop codon and poly(A)-tail both sequences are 97% conserved. At the level of amino acid sequence, the similarity of both, mouse and human, DEAD box family proteins is as high as 98%. In situ hybridizations using cDNA subfragments as probes revealed a testis-selective expression of P68 RNA helicase mRNA. The signal was restricted to late pachytene spermatocytes and haploid spermatids. Northern blot analyses corroborated these results but suggested that expression of related mRNA species occurs in a variety of other tissues. PMID- 8445987 TI - Copulation increases dopamine activity in the medial preoptic area of male rats. AB - Dopamine (DA) metabolites in microdialysates from the medial preoptic area (MPOA) of male rats increased during copulation. These increases were not observed during eating of a highly palatable food, or if the animal failed to copulate, or if the microdialysis probe was anterior or dorsal to the MPOA. The only two animals with measurable serotonin (5-HT) levels while the female was present were also the only two that either failed to copulate or copulated but failed to ejaculate. These data are consistent with previous evidence for a facilitative role of MPOA DA in the control of male sexual behavior; however, 5-HT activity in the MPOA may impair copulation. PMID- 8445988 TI - Effect of ascorbic acid on pituitary prolactin secretion in the non-ascorbate synthesizing Osteogenic Disorder Shionogi (ODS) rat. AB - We examined the secretion of prolactin (PRL) in the hereditary scurvy-prone Osteogenic Disorder Shionogi (ODS) rat to investigate the role of ascorbic acid (AsA) in pituitary lactotroph and hypothalamic function. Plasma PRL concentrations of conscious AsA-deficient or control ODS rats were measured before and after the administration of metoclopramide (MCP), 5-hydroxy-L tryptophan (5-HTP) or saline. The basal plasma PRL levels did not differ between the two groups. However, the AsA-deficient rats exhibited significantly larger changes in plasma prolactin concentration in response to MCP or 5-HTP than the control ODS rats. Thus, AsA deficiency enhanced the stimulated, but not the basal, secretion of PRL in ODS rats. Our findings suggest that AsA may have an inhibitory effect on PRL secretion. PMID- 8445989 TI - Inhibitory effect of a peptide leukotriene antagonist ONO-1078 on LTD4- and antigen-induced thromboxane B2 production in guinea pig lungs. AB - The effect of a peptide leukotriene receptor antagonist ONO-1078 on the production of thromboxane (Tx) B2 induced by leukotriene (LT) D4 and antigen challenge was examined in guinea pig lungs. LTD4 (1-1,000 nM) induced a concentration-dependent production of TxB2 in non-sensitized guinea pig lungs and ovalbumin challenge (0.01-100 micrograms/ml) produced TxB2 and peptide leukotrienes in a concentration-dependent manner in ovalbumin-sensitized guinea pig lungs. ONO-1078 inhibited LTD4 (100 nM)-induced TxB2 production with the IC50 value of 0.24 microM. Furthermore, ONO-1078 inhibited antigen (10 micrograms/ml) induced TxB2 production with the IC50 value of 0.14 microM without effect on the production of peptide leukotrienes. These results suggest that ONO-1078 may prevent the antigen-induced production of TxB2 through the blockade of the activation of receptors by endogenously generated peptide leukotrienes. PMID- 8445990 TI - The relationship of arterial compliance with endothelial-derived proteins of the hemostatic system. AB - Cardiovascular risk factors associated with hypertension include alterations in arterial compliance and an increased tendency to thrombosis. In this study we examined the relationship between arterial compliance and endothelial derived components of the hemostatic system: von Willebrand factor (vWF) and tissue plasminogen activator (t-PA). Ten males (4 normal and 6 untreated hypertensives, 41 +/- 12 years) were studied. Compliance of proximal (large vessel) and distal (small vessel) arteries was measured by intraarterial pulse wave analysis; left ventricular wall thickness by echocardiography; and vWF and t-PA by immunoassay of plasma obtained before and immediately after maximum treadmill exercise. Baseline t-PA and vWF correlated inversely with distal compliance (r = -0.74, p = 0.01; r = -0.56, p = 0.09). Exercise strengthened the relationship between vWF and both distal compliance (r = -0.56 to r = -0.86) and proximal compliance (r = 0.44 to r = -0.70). Moreover, post-exercise levels of vWF and t-PA were each significantly related to left ventricular posterior wall and septal thickness. Of note, these protein concentrations correlated more strongly with arterial compliance and left ventricular wall thickness than with blood pressure. Thus, arterial compliance and left ventricular wall thickness appear to be more powerful than blood pressure as predictors of the endothelial release of vWF and t-PA in response to exercise. These findings indicate that some of the key cardiac and arterial characteristics of hypertension might be linked to increased endothelial reactivity to hemodynamic stress. PMID- 8445991 TI - Effects of ACTH-(1-24) on dopamine and noradrenaline release, B-50 phosphorylation and calmodulin binding to B-50 in vitro. AB - ACTH-(1-24), 1 microM, enhanced the Ca(2+)-dependent release of [3H]dopamine ([3H]DA) from intact septal synaptosomes by approximately 30%, but had no effect on the release of [3H]noradrenaline ([3H]NA) from intact cortical synaptosomes. Since a strong correlation has been reported between B-50 (phosphorylation) and [3H]NA release from intact or streptolysin-O- (SL-O-) permeated cortical synaptosomes, we investigated whether the effects of ACTH-(1-24) on the release of radiolabelled transmitters are mediated by B-50. We observed that the increment in the release of [3H]DA from SL-O-permeated septal synaptosomes as a result of exposure to a high Ca2+ concentration was much less pronounced than that of the release of [3H]NA from SL-O permeated septal and cortical synaptosomes. ACTH-(1-24) concentration-dependently inhibited [3H]NA release from SL-O-permeated cortical synaptosomes (IC50 value of approximately 10 microM) when ACTH-(1-24) was added 150 s prior to the Ca2+ trigger. Simultaneous addition of ACTH-(1-24), SL-O and Ca(2+)-buffers to cortical synaptosomes did not lead to a change in [3H]NA release at any of the ACTH-(1-24) concentrations tested. ACTH-(1 24) had no effect on B-50 phosphorylation in intact synaptosomes, whereas it concentration-dependently inhibited B-50 phosphorylation in permeated cortical synaptosomes (IC50 value of 100 microM). ACTH-(1-24) inhibited (IC50 value of 10 microM) B-50/calmodulin binding in vitro. We conclude that the effects of high concentrations of ACTH-(1-24) on various biochemical B-50 related parameters are not likely to represent the mechanisms underlying the action of ACTH-(1-24) on neurotransmitter release. PMID- 8445992 TI - Blockade by newly-developed antidepressants of biogenic amine uptake into rat brain synaptosomes. AB - We determined the uptake blockade produced by eight new antidepressant drugs (etoperidone, femoxetine, lofepramine, nefazodone, paroxetine, sertraline, tomoxetine, and venlafaxine), two metabolites of newer antidepressants (desmethylsertraline and norfluoxetine), seven previously reported antidepressants, and carbamazepine. Inhibitor constants (Kis) for uptake blockade were obtained from competitive uptake studies with [3H]norepinephrine, [3H]5 hydroxytryptamine, and [3H]dopamine in rat brain synaptosomes prepared from hippocampus, frontal cortex, and striatum, respectively. Among the newer compounds, tomoxetine (Ki = 0.7 nM) and lofepramine (Ki = 1.9 nM) were potent and selective [3H]norepinephrine uptake blockers; paroxetine (Ki = 0.73 nM), sertraline (Ki = 3.4 nM), and femoxetine (Ki = 22 nM) potently and selectively inhibited [3H]5-hydroxytryptamine uptake. Although none of the drugs was potent for [3H]dopamine uptake blockade, sertraline was the most potent (Ki = 260 nM). These data are useful in predicting adverse effects and drug-drug interactions of antidepressants. PMID- 8445993 TI - Hypothermic prevention of the hippocampal damage following ischemia in Mongolian gerbils comparison between intraischemic and brief postischemic hypothermia. AB - The protective effect on ischemic hippocampal damage was compared between intra- and postischemic hypothermia in Mongolian gerbils and its regional preference was evaluated. Male Mongolian gerbils were subjected to transient forebrain ischemia and the hippocampus 7 days after ischemia was examined histologically. In the intraischemic hypothermia (29-31 degrees C) group, CA1 damage was completely prevented in spite of spontaneous postischemic hyperthermia. In contrast, the same degree of brief postischemic hypothermia exerted no preventive effect. While neurons in the subiculum and CA2 sector were also protected against ischemic damage by intraischemic hypothermia, injured pyramidal neurons were always seen in the CA4 sector. PMID- 8445994 TI - Recombinant porcine prorelaxin produced in Chinese hamster ovary cells is biologically active. AB - Although prorelaxin has a similar structure as proinsulin, the posttranslational processing of prorelaxin seems to be quite different from that of proinsulin. There are no pairs of basic residues flanking the relaxin moiety in most prorelaxins studied so far. Instead, the prorelaxins of many species contains a tetrabasic sequence (Arg-Lys-Lys-Arg) between the connecting peptide and the A chain. This is the recognition sequence of furin. In order to study this possible processing by furin, we express the recombinant porcine prorelaxin in Chinese hamster ovary cells. The expected 19 kDa recombinant porcine prorelaxin was found to be constitutively secreted into the medium at a level of approximately 250 ng/ml. No conversion of the 19 kDa prorelaxin into the 6 kDa relaxin was observed. Unlike most prohormones which are biologically inactive, the recombinant prorelaxin was found to be biologically active in an in vitro bioassay. PMID- 8445995 TI - Platelets 3H 5-HT uptake in descendants from alcoholic patients: a potential risk factor for alcohol dependence? AB - We studied platelet 3H-serotonin uptake in 32 former alcoholics, withdrawn for from 1 month to 22 years, in their descendants (21.7 +/- 1.6 years old, n = 17; 10.9 +/- 0.7 years old; n = 19), and in respective control groups, paired in age and sex. All of the alcoholics presented high 3H-serotonin uptake (Vmax = 10.88 +/- 4.23 pmoles/10(8)pl/30 sec., vs. 0.93 +/- 0.15 pmole/10(8)pl/30 sec. Their descendants also showed high platelet serotonin uptake: 3.94 +/- 1.44 pmoles/10(8)pl/30 sec., vs. 0.93 +/- 0.15 pmoles/10(8)pl/30 sec. for adult descendants, and 5.99 +/- 2.23 vs. 0.84 +/- 0.15 pmole/10(8)pl/30 sec. for young descendants. All subjects were free of alcoholisation (biological parameters studied were blood ethanol concentration, gamma glutamyl transferase and mean corpuscular volume), and dependence of former alcoholics was evaluate by using, a posteriori, the CAGE test. In descendants, 28% of the subjects have Vmax values higher than the highest of the control group. Alcohol, in vitro, (54 mM) did not affect serotonin uptake in any group. These results indicate that in descendants of alcoholics, platelet serotonin uptake is altered, without modification of sensitivity to ethanol. The genetic basis of alcohol dependence could be linked with the platelet serotonin transport. PMID- 8445996 TI - Effect of 5-HT-1A receptor agonists on paw licking reaction on hot plate and unpunished drinking in rat. AB - 5-HT-1A receptor agonists suppress the rat hind paw licking reaction on a hot plate and unpunished drinking in thirsty rats with the order of potency: 8-OH DPAT > Ru 24.969 > buspirone > gepirone > ipsapirone. The behavioral activity of these drugs is in agreement with their affinity for [3H] 8-OH-DPAT binding sites with the exception of ipsapirone, which is a partial agonist at the 5-HT-1A receptor. Our data and data reported previously indicate that the effects of 5-HT 1A agonists in both behavioral tests can not be attributed to the reduction of pain sensitivity or to the inhibition of locomotor activity. It is suggested that the observed effects may reflect the suppression of an emotional-motivational component of animal behavior. PMID- 8445997 TI - Does midazolam inhibit the development of acute tolerance to the analgesic effect of alfentanil? AB - Alfentanil-midazolam analgesic interactions were studied in rats with continuous infusions or bolus injections of the drugs. Analgesia was determined by measuring the threshold of motor response to noxious pressure. The continuous constant-rate infusion of alfentanil demonstrated that after an initial peak, the analgesia profoundly declined due to the development of acute tolerance. When alfentanil (250 micrograms.kg-1.h-1) was given together with midazolam (3 mg.kg-1.h-1), the decline in the analgesic effect of alfentanil was attenuated. Following the 4 h period of the constant-rate (250 micrograms.kg-1.h-1) infusion of alfentanil, when acute tolerance was already developed, midazolam (3 mg.kg-1) given as a bolus injection enhanced the alfentanil-induced anesthesia. At the same time, when alfentanil was given as a bolus injection (30 micrograms.kg-1) with or without midazolam (3 mg.kg-1) also by bolus injection, no changes were seen to indicate an enhancement of the analgesic effect of alfentanil by midazolam. The results suggest that midazolam attenuates the development of acute tolerance to the analgesic effect of alfentanil. PMID- 8445998 TI - Suppressive effect of GABA on insulin secretion from the pancreatic beta-cells in the rat. AB - In order to investigate a possible role of GABA in the regulation of insulin secretion, we have studied the effect of GABA on insulin secretion from the isolated perfused rat pancreas in vitro and on the changes in the cytoplasmic Ca2+ of Beta-cells from the isolated rat islets. When glucose is present, GABA caused a dose dependent inhibition of the first phase of arginine-induced insulin secretion during the range of 10-1000 microM, but GABA did not affect arginine induced insulin secretion in the absence of glucose. GABA inhibited not only the first phase but also the second phase of glucose-induced insulin secretion. A GABAB-receptor agonist, baclofen, also inhibited both phases of insulin secretion induced by 16.7 mM glucose. Furthermore, GABA inhibited the rise in cytoplasmic Ca2+ of Beta-cells in response to 16.7 mM glucose. These studies indicate that GABA decreases Beta cell secretory activity mainly in response to glucose. These inhibitory effects of GABA on insulin secretion may be mediated through GABAB receptor and the inhibition of the rise in cytoplasmic Ca2+. PMID- 8445999 TI - Effects of chronic morphine on biliary tract responses to cholecystokinin octapeptide in female guinea pigs. AB - Acute and chronic opiates impairs the emptying of bile from the gallbladder of male guinea pigs. In view of the higher incidence of gallstone attacks in women, the aim of this study was to determine if this impairment would extend to female guinea pigs. Implantation of morphine pellets (400mg) in female guinea pigs did depress CCK-induced emptying of gallbladder bile. Likewise, gallbladder muscle strips isolated from the morphine treated animals showed depressed responses to CCK. The morphine treatment also antagonized CCK-induced cessation of bile flow present in female guinea pigs. In addition, the morphine treatment blocked both CCK-induced phasic contractions of the isolated isolated Sphincter of Oddi and the secondary cessation of bile flow observed following iv CCK. Thus this study demonstrates that opiate antagonism of CCK does extend to the biliary tract of female guinea pigs, and suggests that resultant biliary stasis could facilitate gallstone formation. PMID- 8446000 TI - Enhanced lithogenicity of bile following chronic morphine administration to female guinea pigs. AB - Acute and chronic opiate exposure impairs the emptying of bile from the gallbladder. In this study, the effects of a 4-day morphine regimen on bile composition were examined. Bile acids and phospholipids concentration of bile obtained from the gallbladder of female morphine-treated (MT) guinea pigs were reduced by 60% and 80% respectively, resulting in a highly lithogenic bile. Concentrations of bile acids and phospholipids of spontaneously secreted bile were not reduced. However, the lithogenicity of the hepatic bile in MT animals was still increased because of a 10 fold elevation in cholesterol concentration. Ratios of solute concentrations of stored and freshly secreted bile indicated that morphine also impaired the ability of the gallbladder to concentrate bile. Thus chronic morphine exposure increased bile lithogenicity by increasing cholesterol content and also by diluting the bile in the gallbladder. These alterations and the previously described biliary stasis indicates that chronic opiate and endogenous opioid exposure should facilitate gallstone formation. PMID- 8446001 TI - Antihypertensive effect of a newly synthesized endothelin antagonist, BQ-123, in a genetic hypertensive model. AB - A newly synthesized ET(A)-selective antagonist, BQ-123, was examined with respect to its anti-endothelin(ET) action in vitro and in vivo and its effect on blood pressure in Wistar Kyoto rats (WKY), spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SHRSP). In isolated porcine coronary arteries, BQ-123 (0.07 microM to 6.0 microM) shifted the concentration response curve for ET-1 to the right without affecting the maximal response of ET 1, its pA2 value being 7.35. Intravenous infusion of BQ-123 at a rate of 1.2 and 30 mg/kg/hr produced a significant decrease in blood pressure in 20- to 29-week old SHRSP, but did not alter blood pressure in 13- to 16-week-old WKY or in 18- to 19-week-old and 40-week-old SHR. The hypotensive effect of BQ-123 depended on the pretreatment blood pressure level. These results suggest that ET-1 is involved in part in the maintenance of high blood pressure in malignant hypertension, as exemplified by SHRSP. PMID- 8446002 TI - Effect of bombesin antagonist D-Phe6-BN(6-13)OMe on vagally induced gastrin release from perfused rat stomach. AB - The aim of the present study was to evaluate the effect of the bombesin antagonist D-Phe6-BN(6-13)OMe (BN-antagonist) on vagally stimulated gastrin release from the isolated rat stomach, which was perfused via the celiac artery with Krebs-Ringer buffer. Vagal stimulation was performed for 10 minutes with 1 ms, 10 V and 10 or 2 Hz, respectively. Gastrin secretion increased significantly during stimulation with 10 and 2 Hz. BN-antagonist was added to the perfusate at the concentration of 10(-6) M, which induced a significant reduction of vagally stimulated gastrin release at 10 Hz (619 +/- 65 vs. 252 +/- 62 pg/10 min, p < 0.05), but not at 2 Hz (564 +/- 117 vs. 493 +/- 113 pg/10 min, p > 0.05). In contrast, atropine (10(-7) M) reduced significantly the gastrin response at 2 Hz (270 +/- 78 pg/10 min, p < 0.01), but not at 10 Hz (446 +/- 87 pg/10 min, p > 0.05). The combination of BN-antagonist and atropine elicited an inhibition of vagally stimulated gastrin release similar to each substance when given alone. Basal gastrin release was not changed by the BN-antagonist. The present data suggest, that in the rat stomach endogenously released bombesin-related peptides contribute to the noncholinergic stimulation of gastrin release at higher stimulation frequencies (10 Hz), however, bombesin-related peptides are not involved, when lower stimulation frequencies (2 Hz) are employed. At both stimulation frequencies additional mechanisms are activated which are noncholinergic and not related to bombesin peptides. PMID- 8446003 TI - Occurrence of free D-aspartic acid in the circumsoesophageal ganglia of Aplysia fasciata. AB - This study reports the presence of high concentrations of free D-aspartic acid (D Asp) in the circumoesophageal ganglia of the opisthobranch mollusc Aplysia fasciata. D-Asp was discovered using specific methods that employ Octopus D aspartate oxidase and hog kidney D-amino acid oxidase to measure D-Asp levels. The concentration of D-Asp was 0.281 mumol/g wet tissue weight, which was 8.3% of the total free aspartic acid (D and L forms) present. No other free D-amino acids that were oxidised by D-amino acid oxidase were detected. To our knowledge the only molluscs that have previously been shown to have D-Asp within their nervous tissue are the cephalopods Octopus vulgaris, Loligo vulgaris and Sepia officinalis. In these, as in A. fasciata, no other D-amino acids were detected within the nervous tissue. The fact that free D-Asp occurs specifically in the nervous tissue of the above molluscs suggests that it may have a neurological function that is yet to be described. PMID- 8446004 TI - Effect of cocaine on leakage of creatine kinase from isolated fast and slow muscles of rat. AB - Since patients with cocaine overdose were reported to develop rhabdomyolysis involving skeletal muscle damage leading to elevated levels of serum creatine kinase (CK), we determined whether cocaine can directly act on isolated rat skeletal muscles and increase the leakage of CK. In the fast-twitch muscle such as the extensor digitorum longus (EDL), following exposure to normal physiological solution for 1, 2, 3, and 4 hr, the mean leakage of CK was 0.6, 0.7, 0.9, and 1.2 units/mg of muscle respectively. On exposure of EDL to 0.1, 0.5, and 1.0 mM cocaine, there was no significant change in CK leakage. In the slow-twitch muscle such as the soleus, following exposure to normal physiological solution for 1, 2, 3, and 4 hr, the mean leakage of CK was 1.5, 2.2, 2.7, and 3.1 units/mg, which was significantly greater (P < 0.001) than in EDL at each time interval. On exposure of soleus to 0.1 mM cocaine, the CK leakage did not increase significantly, but on exposure to 0.5 mM cocaine, it significantly increased to 2.4, 3.4, 4.4, and 5.7 units/mg, and on exposure to 1.0 mM cocaine, it further increased to 2.7, 4.9, 6.5, and 7.6 units/mg. The CK activity of fresh muscle homogenate was 115.5 units/mg in EDL and 51.9 units/mg in soleus. These results indicate that cocaine can directly act on skeletal muscle and increase the leakage of CK especially from slow-twitch muscle like soleus, but not from fast-twitch muscle like EDL. PMID- 8446005 TI - Incorporation of oleic acid and eicosapentaenoic acid into glycerolipids of cultured normal human fibroblasts. AB - Confluent skin fibroblasts from normal humans were incubated in serum free medium with up to 100 nmole/mL eicosapentaenoic acid (EPA; bound to albumin in a 4.6:1 ratio) and compared with cells incubated with oleic acid (OA) at similar concentrations. The rate of [14C]OA incorporation into triacylglycerol (TG) (nmol/mg/h) was approximately 5-fold greater than that of [14C]EPA. The mass of TG formed after incubation of fibroblasts with EPA was also significantly lower than that formed with OA (43.2 +/- 9.3 vs. 59.5 +/- 6.6 micrograms/mg cell protein, respectively, P = 0.006). The addition of excess, unlabeled EPA reduced the rate of incorporation of [14C]OA into TG whereas unlabeled OA stimulated incorporation of [14C]EPA into TG. When the cells were preincubated with human serum basic proteins (BP I, II and III), the mass of TG formed (compared to baseline) was significantly higher with the basic proteins whether OA or EPA was studied. Only BP I significantly stimulated the mass of cell phospholipids, an effect that occurred with either OA or EPA in the medium. The results suggest that in cultured normal human fibroblasts, OA is a better substrate for TG synthesis than EPA and that this effect may be accentuated by the presence of the basis proteins. PMID- 8446006 TI - Molecular species composition of glycerophospholipids from white matter of human brain. AB - The molecular species composition of the major glycerophospholipids from white matter of human brain were determined by high-performance liquid chromatography of the 3,5-dinitrobenzoyl derivatives of the corresponding diradylglycerols. In phosphatidylcholine (PC) and phosphatidylserine (PS), molecular species containing only saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) comprised 85.7 and 82.4% of the respective totals, with 18:0/18:1 predominant in PS and 16:0/18:1 in PC. These molecular species were also abundant in phosphatidylethanolamine (PE), but in this phospholipid species containing polyunsaturated fatty acids (PUFA), largely 18:0/22:6n-3 and 18:0/20:4n-6, accounted for over half the total; 18:1/18:1 was also abundant in PE. In contrast, 1-O-alk-1'-enyl-2-acyl sn-glycero-3-phosphoethanolamine (GPE) had much more SFA- and MUFA-containing species, predominantly 16:0a/18:1, 18:0a/18:1 and 18:1a/18:1, with low amounts of species containing 20:4n-6 and 22:6n-3. In alkenylacyl GPE, 22:4n-6 was the major PUFA and 16:0a/22:4n-6 and 18:1a/22:4n-6 the main PUFA-containing species. There was six times more 22:6n-3, twice as much 20:4n-6 and half the amount of 22:4n-6 in PE as compared to alkenylacyl GPE. PMID- 8446007 TI - Phospholipids in Drosophila heads: effects of visual mutants and phototransduction manipulations. AB - A procedure was developed to label phospholipids in Drosophila heads by feeding radioactive phosphate (32Pi). High-performance thin-layer chromatography showed label incorporation into various phospholipids. After 24 h of feeding, major phospholipids labeled were phosphatidylethanolamine (PE), 47%; phosphatidylcholine (PC), 24%; and phosphatidylinositol (PI), 12%. Drosophila heads have virtually no sphingomyelin as compared with mammalian tissues. Notable label was in ethanolamine plasmalogen, lysophosphatidylethanolamine, lysophosphatidylcholine and lysophosphatidylinositol. Less than 1% of the total label was in phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5 bisphosphate. Other lipids labeled included phosphatidylserine, phosphatidic acid and some unidentified lipids. A time course (3-36 h) study revealed a gradual decrease in proportion of labeled PI, an increase in proportion of labeled PC and no obvious change in labeled PE. There were no significant differences in phospholipid labeling comparing the no receptor potential (norpA) visual mutant and wild type under light vs. dark conditions. However, overall 32P labeling was higher in the wild type fed in the light as compared to the dark and to norpA either in light or dark. This suggests that functional vision facilitates incorporation of label. Differences in phospholipid labeling were observed between young and aged flies, particularly in lysophospholipids and poly-PI, implicating phospholipase A2 function in recycling. v Manipulations such as the outer rhabdomeres absent and eyes absent mutants and carotenoid deprivation failed to yield notable differences in phospholipid labeling pattern, suggesting that phospholipids important to vision may constitute only a minor portion of the total labeled pool in the head. PMID- 8446008 TI - Stereospecificity of monoacylglycerol and diacylglycerol acyltransferases from rat intestine as determined by chiral phase high-performance liquid chromatography. AB - Using chiral phase high-performance liquid chromatography of diacylglycerols, we have redetermined the ratios of 1,2-/2,3-diacyl-sn-glycerols resulting from acylation of 2-monoacylglycerols by membrane bound and solubilized triacylglycerol synthetase of rat intestinal mucosa. With 2-oleoyl[-3H]glycerol as the acyl acceptor and oleoyl-CoA as the acyl donor, 97-98% of the diacylglycerol product was 1,2(2,3)-dioleoyl-sn-glycerol, 90% of which was the sn 1,2- and 10% the sn-2,3-enantiomer. The remaining diacylglycerol (less than 3%) was the sn-1,3-isomer. The overall yield of acylation products was 70%, of which 60% were diacylglycerols and 40% triacylglycerols. With 2-oleylglycerol ether as the acyl acceptor and [1-14C]oleoyl-CoA as the acyl donor, 90% of the diradylglycerol was 1-oleoyl-2-oleyl-sn-glycerol and 10% was the 2-oleyl-3-oleoyl sn-glycerol. The diradylglycerols made up 96% and the triradylglycerols 4% of the radioactive product. With 1-palmitoyl-sn-glycerol as the acyl acceptor and [1 14C]oleoyl-CoA as the acyl donor, the predominant reaction product was 1 palmitoyl-3-oleoyl-sn-glycerol. The 3-palmitoyl-sn-glycerol was not a suitable acyl acceptor. Both 1,2- and 2,3-diacyl-sn-glycerols were substrates for diacylglycerol acyltransferase as neither isomer was favored when 1,2-dioleoyl rac-[2-3H]glycerol was used as the acyl acceptor. There was a marked decrease in the acylation of the 1(3)-oleoyl-2-oleyl-sn-glycerol to the 1,3-dioleoyl-2-oleyl sn-glycerol. It is concluded that neither monoacylglycerol nor diacylglycerol acyltransferase exhibit absolute stereospecificity for acylglycerols as fatty acid acceptors. PMID- 8446009 TI - Multigram synthesis of 1-alkylamido phospholipids. AB - Phospholipids containing a 1-alkylamido linkage have shown promising in vitro neoplastic cell growth inhibitory properties and anti-human immunodeficiency viral activity. We have synthesized a series of alkylamido ether lipid analogues on a milligram scale for initial evaluation, but for further in vivo testing of these bioactive phospholipids, synthesis on a larger scale is required. The multigram synthesis of 1-alkylamido ether phospholipids was accomplished by modifying reaction conditions in the amidation step and changing reagents and solvent systems in both the detritylation and phosphorylation steps. This was most crucial in the phosphorylation step, where in the multigram synthesis 2 bromoethyl dichlorophosphate in diethyl ether/tetrahydrofuran (7:3, vol/vol) gave much improved yields as compared to the 2-chloro-2-oxo-1,3,2-dioxaphospholane reagent. The modifications also resulted in a product that could be more easily purified in sufficient quantities for use in in vivo inhibition studies. PMID- 8446010 TI - Effect of simvastatin on desaturase activities in liver from lean and obese Zucker rats. AB - The effect of simvastatin, a hypocholesterolemic drug, on the biosynthesis of arachidonic acid was studied in obese and lean Zucker rats. After administration of 2 mg/kg body weight/d for 13 d, delta 6 and delta 5 desaturase activities were measured in liver microsomes at two substrate concentrations. In untreated rats, the delta 6 desaturation rate was similar in the obese and lean rats when measured at saturating substrate levels, whereas delta 5 desaturation was lower in the obese animals. Treatment with simvastatin did not change delta 6 desaturation in either phenotype but increased delta 5 desaturation in obese rats to reach the unchanged rate observed in lean animals. The changes were not reflected in the fatty acid composition of liver microsomal phospholipids when expressed as micrograms fatty acid/g of liver. PMID- 8446011 TI - Composition of the phospholipids and their fatty acids in the ROC-1 oligodendroglial cell line. AB - ROC-1 cells are a hybrid of C-6 rat glioma and rat oligodendroglia cells. Biochemically these cells resemble the oligodendroglia parent, but their lipid composition is unknown. The phospholipid composition in mole % was: cardiolipin, 1.0; phosphatidylglycerol, 1.2; ethanolamine glycerophospholipids, 27.6; phosphatidylinositol, 5.8; lysophosphatidylethanolamine, 0.8; phosphatidylserine, 5.6; choline glycerophospholipids, 43.7; sphingomyelin, 13.7; phosphatidylinositol-4-monophosphate, 0.8; and lysophosphatidylcholine, 0.6. The choline and ethanolamine plasmalogens made up 7.2 and 18.4% of the total phospholipids, respectively. The phospholipid composition reflects that of both parental cells. The cells had moderate to high levels of 20:3n-9 indicating n-6 series fatty acid deficiency. The phosphatidylinositol had very high 20:3n-9 levels with a 20:3n-9/20:4n-6 ratio of 2.1 compared to 0.44 and 0.58 for ethanolamine glycerophospholipids (EtnGpl) and choline glycerophospholipids (ChoGpl) respectively. The saturated/polyenoic fatty acid ratios were 0.40 for EtnGpl, 3.38 for ChoGpl and 1.48 for phosphatidylinositol. PMID- 8446012 TI - Influence of dietary egg and soybean phospholipids and triacylglycerols on human serum lipoproteins. AB - Human serum lipid and lipoprotein concentrations and compositions were compared in ten healthy middle-aged men consuming phospholipids from egg or from soybean or triacylglycerol mixtures with fatty acid compositions similar to that of the phospholipids. All subjects followed each of the four treatments: egg phospholipids (EP), soybean phospholipids (SP), an oil of fatty acid composition similar to that of EP, and an oil similar in fatty acid composition to SP for six weeks with "wash-out" periods of similar duration between treatment periods. The phospholipids, 15 g/d, and the oils, 12 g/d, which contained approximately equivalent quantities of fatty acids were provided to the subjects in gelatin capsules and were taken before meals. Diet intake was monitored by three-day food records. Serum lipoproteins (Lp) were separated by ultracentrifugation into very low density lipoproteins, low density lipoproteins (LDL), high density lipoproteins (HDL)2 and HDL3. Lp fractions and whole serum were analyzed for triacylglycerols, cholesterol (CH), phospholipids (PL), and protein. HDL cholesterol was determined in whole serum. Cholesteryl esters were determined in some Lp fractions. Lipid compositions of Lp were expressed in mmol/g protein. Apoprotein B was measured in whole serum and in LDL; apoprotein A-I in whole serum and in HDL3. In whole serum, CH and PL were significantly lower after the SP compared to EP treatment periods. CH, but not PL, was lower after SPTG compared to EP. CH in HDL2 was significantly higher after SP compared to SPTG. Also, PL in HDL2 were significantly higher after SP compared to all other treatments and to baseline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446013 TI - A simple and efficient synthesis of fatty thioacids. AB - A rapid and high-yielding two-step synthesis of fatty thioacids from readily available starting materials has been devised. In the first step, an acid chloride is reacted with thioacetic acid at room temperature to produce a mixed thioanhydride, which in the second step is nucleophilically deacetylated with propylamine or butylamine at 5 degrees C. Each step is complete in five minutes and proceeds in quantitative yield. The versatility of the procedure is demonstrated by the synthesis of fatty thioacids from six to sixteen carbons in length. PMID- 8446015 TI - Is a lobbyist really necessary? PMID- 8446014 TI - University of Maryland's experience with chorionic villus sampling: a different view of this questionable procedure. PMID- 8446016 TI - Have you come a long way, baby? Smoking trends in women. AB - The relative risks of smoking-related diseases are increasing for women as the ratio of men smokers to women smokers closes. In addition, recognition of smoking as a women's health risk has increased because of its adverse effects in pregnancy; its interaction with oral contraceptives; and its association with cancer of the uterine cervix, earlier menopause, and osteoporosis. PMID- 8446017 TI - HIV disease in pregnancy. AB - The years from 1981 to the present have seen a steady increase in the incidence of AIDS in the female population. The corollary increase in the incidence of AIDS in pregnancy increases the responsibility of the obstetrician to become aware of the effect of AIDS on pregnancy and the effect of pregnancy on AIDS. PMID- 8446018 TI - The history of brucellosis in Maryland and the District of Columbia. AB - The history of brucellosis began in Europe; however, a number of early studies and publications originated in medical centers in Maryland and the District of Columbia. As a result of efforts by researchers in these locales, physicians came to understand the transmission of the disease, and continued clinical investigations helped to develop significant therapeutic and preventive measures that have made brucellosis a rare disease in the United States. PMID- 8446019 TI - Giardiasis: a case report and discussion of outbreaks in the United States. AB - Outbreaks of giardiasis occur every year in the United States, and waterborne infections appear to be increasing. Accurate identification of cases, proper hygiene in day-care and institutional settings, and adequate treatment of water sources will allow better control of this disease. PMID- 8446020 TI - The homes of the Medical and Chirurgical Faculty of Maryland. AB - Through its almost 200-year existence, the Med Chi Faculty has met in numerous locations in Annapolis and Baltimore. The building at 1211 Cathedral Street has been its home for 84 years. PMID- 8446021 TI - A 37-year-old man with diabetes mellitus, renal transplant, fever, pulmonary infiltrates, and mental status alterations. PMID- 8446022 TI - Imaging case of the month. Impingement syndrome. PMID- 8446023 TI - The activities of the Medical and Chirurgical Faculty. 1952. PMID- 8446024 TI - SecA protein: autoregulated ATPase catalysing preprotein insertion and translocation across the Escherichia coli inner membrane. AB - Recent insight into the biochemical mechanisms of protein translocation in Escherichia coli indicates that SecA ATPase is required both for the initial binding of preproteins to the inner membrane as well as subsequent translocation across this structure. SecA appears to promote these events by direct recognition of the preprotein or preprotein-SecB complex, binding to inner-membrane anionic phospholipids, insertion into the membrane bilayer and association with the preprotein translocator, SecY/SecE. ATP binding appears to control the affinity of SecA for the various components of the system and ATP hydrolysis promotes cycling between its different biochemical states. As a component likely to catalyse a rate-determining step in protein secretion, SecA synthesis is co ordinated with the activity of the protein export pathway. This form of negative regulation appears to rely on SecA protein binding to its mRNA and repressing translation if conditions of rapid protein secretion prevail within the cell. A precise biochemical scheme for SecA-dependent catalysis of protein export and the details of secA regulation appear to be close at hand. The evolutionary conservation of SecA protein among eubacteria as well as the general requirement for translocation ATPases in other protein secretion systems argues for a mechanistic commonality of all prokaryotic protein export pathways. PMID- 8446025 TI - Isolation of a prokaryotic metallothionein locus and analysis of transcriptional control by trace metal ions. AB - In eukaryotes, metallothioneins (MTs) are involved in cellular responses to elevated concentrations of certain metal ions. We report the isolation and analysis of a prokaryotic MT locus from Synechococcus PCC 7942. The MT locus (smt) includes smtA, which encodes a class II MT, and a divergently transcribed gene, smtB. The sites of transcription initiation of both genes have been mapped and features within the smt operator-promoter region identified. Elevated concentrations of the ionic species of Cd, Co, Cr, Cu, Hg, Ni, Pb and Zn elicited an increase in the abundance of smtA transcripts. There was no detectable effect of elevated metal (Cd) on smtA transcript stability. Sequences upstream of smtA, fused to a promoterless lacZ gene, conferred metal-dependent beta-galactosidase activity in Synechococcus PCC 7942 (strain R2-PIM8). At maximum permissive concentrations, Zn was the most potent elicitor in vivo, followed by Cu and Cd with slight induction by Co and Ni. The deduced SmtB polypeptide has similarity to the ArsR and CadC proteins involved in resistance to arsenate/arsenite/antimonite and to Cd, contains a predicted helix-turn-helix DNA binding motif and is shown to be a repressor of transcription from the smtA operator-promoter. PMID- 8446026 TI - Deletion within the metallothionein locus of cadmium-tolerant Synechococcus PCC 6301 involving a highly iterated palindrome (HIP1). AB - Genomic rearrangements involving amplification of metallothionein (MT) genes have been reported in metal-tolerant eukaryotes. Similarly, we have recently observed amplification and rearrangement of a prokaryotic MT locus, smt, in cells of Synechococcus PCC 6301 selected for Cd tolerance. Following the characterization of this locus, the altered smt region has now been isolated from a Cd-tolerant cell line, C3.2, and its nucleotide sequence determined. This has identified a deletion within smtB, which encodes a trans-acting repressor of smt transcription. Two identical palindromic octanucleotides (5'-GCGATC-GC-3') traverse both borders of the excised element. This palindromic sequence is highly represented in the smt locus (7 occurrences in 1326 nucleotides) and analysis of the GenBank/EMBL/DDBJ DNA Nucleotide Sequence Data Libraries reveals that this is a highly iterated palindrome (HIP1) in other known sequences from Synechococcus strains (estimated to occur at an average frequency of once every c. 664 bp). HIP1 is also abundant in the genomes of other cyanobacteria. The functional significance of smtB deletion and the possible role of HIP1 in genome plasticity and adaptation in cyanobacteria are discussed. PMID- 8446027 TI - Use of an ordered cosmid library to deduce the genomic organization of Mycobacterium leprae. AB - In an attempt to unify the genetic and biological research on Mycobacterium leprae, the aetiological agent of leprosy, a cosmid library was constructed and then ordered by a combination of fingerprinting and hybridization techniques. The genome of M. leprae is represented by four contigs of overlapping clones which, together, account for nearly 2.8Mb of DNA. Several arguments suggest that the gaps between the contigs are small in size and that virtually complete coverage of the chromosome has been obtained. All of the cloned M. leprae genes have been positioned on the contig maps together with the 29 copies of the dispersed repetitive element, RLEP. These have been classified into four groups on the basis of differences in their organization. Several key housekeeping genes were identified and mapped by hybridization with heterologous probes, and the current genome map of this uncultivable pathogen comprises 72 loci. PMID- 8446028 TI - Nucleotide sequence of the first cosmid from the Mycobacterium leprae genome project: structure and function of the Rif-Str regions. AB - The nucleotide sequence of cosmid B1790, carrying the Rif-Str regions of the Mycobacterium leprae chromosome, has been determined. Twelve open reading frames were identified in the 36716bp sequence, representing 40% of the coding capacity. Five ribosomal proteins, two elongation factors and the beta and beta' subunits of RNA polymerase have been characterized and two novel genes were found. One of these encodes a member of the so-called ABC family of ATP-binding proteins while the other appears to encode an enzyme involved in repairing genomic lesions caused by free radicals. This finding may well be significant as M. leprae, an intracellular pathogen, lives within macrophages. PMID- 8446029 TI - The general amino acid control regulates MET4, which encodes a methionine-pathway specific transcriptional activator of Saccharomyces cerevisiae. AB - A met4 mutant of Saccharomyces cerevisiae was unable to transcribe a number of genes encoding enzymes of the methionine biosynthetic pathway. The sequence of the cloned MET4 gene allowed the previously sequenced flanking LEU4 and POL1 genes to be linked to MET4 into a 10,327 bp contiguous region of chromosome XIV. From the sequence and mapping of the transcriptional start points, MET4 is predicted to encode a protein of 634 amino acids (as opposed to 666 amino acids published by others) with a leucine zipper domain at the C-terminus, preceded by both acidic and basic regions. Thus, MET4 belongs to the family of basic leucine zipper trans-activator proteins. Disruption of MET4 resulted in methionine auxotrophy with no other phenotype. Transcriptional studies showed that MET4 was regulated by the general amino acid control and hence by another bZIP protein encoded by GCN4. GCN4 binding sequences are present between the divergently transcribed MET4 and LEU4 genes. Over-expression of MET4 resulted in leaky expression from the otherwise tightly regulated MET3 promoter under its control. The presence of consensus sequences for other potential regulatory elements in the MET4 promoter suggests a complex regulation of this gene. PMID- 8446030 TI - Suppression of rpsL phenotypes by tuf mutations reveals a unique relationship between translation elongation and growth rate. AB - We have found a simple relationship between bacterial growth rate and the translation elongation rate. Thus, for a set of defined ribosomal protein S12 mutations which reduce the efficiency of the ternary complex ribosome interaction (and restrict the frequency of translational errors) there is a linear relationship between growth rate and translation elongation rate. When these mutants are combined with defined EF-Tu mutants (which increase the probability of translational errors) both the elongation rate and growth rate reductions are reversed. The reductions and reversals are described by a unique linear relationship. We interpret this to mean that these two types of mutation exert opposing effects on the same molecular interaction. We suggest that this interaction is in the initial selection of the aminoacyl-tRNA on the ribosome. The slope of the relationship between translation elongation rate and growth rate, defined in per cent of the wild-type rates, is close to 1. Interestingly, the reversal of the elongation and growth phenotypes is incomplete, suggesting that the ribosomal mutants have an additional defect which is not compensated for by the ternary complex interaction. Our results show that the efficiency of the ternary complex ribosome interaction limits the translation elongation rate, which in turn correlates with changes in exponential growth rate. PMID- 8446031 TI - The origin of greater-than-unit-length plasmids generated during bacterial conjugation. AB - In Gram-negative bacteria, the general mechanism of conjugal plasmid transfer, which is probably similar for many different groups of plasmids, involves the transfer of a single plasmid DNA strand with 5' to 3' polarity. Transfer is initiated by nicking of the duplex DNA at a particular site, i.e. the origin of transfer (oriT). We constructed plasmids containing two directly repeated copies of oriT, derived from the broad-host-range plasmid R1162 and flanking the lac operator. The number of lacO copies in the plasmid after transfer could be determined from the colour of transconjugant colonies on medium containing X-Gal. When the oriTs were mutated to prevent initiation and termination of transfer at the same oriT, almost all of the transconjugant cells contained greater-than-unit length plasmids with two copies of lacO and three copies of oriT. We show that these molecules were generated by an intramolecular, conjugation-dependent mechanism unlikely to depend solely on a pre-existing population of circular or linear multimers in donor cells. We propose that the greater-than-unit-length molecules were instead generated by a rolling-circle mechanism of DNA replication. PMID- 8446032 TI - Signalling of Trichomonas vaginalis for amoeboid transformation and adhesion synthesis follows cytoadherence. AB - The cytoadherence of Trichomonas vaginalis, the sexually transmitted flagellated protozoan, to vaginal epithelial cells (VECs) is the key to infection. Electron microscopy revealed that in vitro-grown parasites having typical globular shape transformed rapidly after contact with VECs into thin, flat, amoeboid cells, maximizing the area of adhesion to the surface of VECs. Amoebic trichomonads formed filopodia and pseudopodia, which interdigitated at distinct sites on the plasma membrane of target cells. In contrast, the amoeboid transformation did not occur for T. vaginalis interacting with HeLa cells, the previously used in vitro host model cell. Initial parasitism of VECs by a single organism was followed by establishment of a monolayer of trichomonads on the host cell. Finally, parasites adhering to either VECs or HeLa cells were induced to synthesize greater amounts of the four previously described adhesins. Therefore, distinct signals after contact with either epithelial cell type leads to the morphological transformation and/or induction of adhesion synthesis by T. vaginalis. PMID- 8446034 TI - Bafilomycin A1 inhibits Helicobacter pylori-induced vacuolization of HeLa cells. AB - Bafilomycin A1, a specific inhibitor of the vacuolar-type H(+)-ATPase, responsible for acidification of intracellular compartments, prevents the vacuolization of Hela cells induced by H. pylori, with an inhibitory concentration giving 50% of maximal (ID50) of 4 nM. Bafilomycin A1 is also very efficient in restoring vacuolated cells to a normal appearance. The vacuolating activity of Helicobacter pylori is not inhibited by a series of specific inhibitors of vacuolar H(+)-ATPases. These findings indicate that a transmembrane pH gradient is needed for the formation and growth of vacuoles caused by the bacterium and that this pH gradient is due to the activity of a vacuolar ATPase proton pump of HeLa cells. PMID- 8446033 TI - Regulation of transcription of genes required for fatty acid transport and unsaturated fatty acid biosynthesis in Escherichia coli by FadR. AB - Fatty acid biosynthesis and fatty acid degradation in Escherichia coli are co ordinately regulated at the level of transcription by the product of the fadR gene, FadR. In the present work we investigate FadR interaction with the fabA and fadL promoters. The FadR-responsive operator within fabA, OA, was localized to a region -47 to -31 base pairs relative to the start of transcription using DNase I protection studies. The promoter and untranslated leader within fadL had two binding sites for FadR, OL1 at -25 to -9 and OL2 at -1 to +16 relative to the start of transcription. The binding affinity of FadR for OA and OL1 or OL2 was lower than that for the single site within fadB (OB) as measured using protein DNA gel retention assays. Overall, these experiments demonstrated that the affinity of FadR binding for DNA containing the fadB, fadL and fabA promoters was OB > OL1, OL2 > OA. We could not distinguish separate binding affinities for OL1 or OL2. We demonstrated repression of fadL transcription and activation of fabA transcription in vitro using run-off transcription assays containing purified FadR and RNA polymerase. PMID- 8446035 TI - Genetic analysis of the phi C31-specific phage growth limitation (Pgl) system of Streptomyces coelicolor A3(2). AB - The phage growth limitation (Pgl) system of Streptomyces coelicolor A3(2) was shown to be specific to phi C31 homo-immune phages, and to be absent from the closely related strain Streptomyces lividans. A 16 kb fragment of S. coelicolor A3(2) DNA was isolated which complemented the Pgl- phenotype of J1501, a pgl mutant derivative of the Pglts S. coelicolor strain M130. The cloned DNA complemented only half of the available pgl mutants, which therefore represented at least two groups, designated Pgl class A and class B strains. It follows that more than one kind of high-frequency genetic event can lead to the Pgl- phenotype. Crosses between class A and class B strains yielded high frequencies of Pgl+ recombinants. Crosses between strains of the same class gave no Pgl+ recombinants. The cloned DNA was altered by deletion or apparent point mutation upon passage through the two class B strains tested, such that it was no longer capable of complementing class A strains. This accumulation of mutations might suggest that the expression of the cloned DNA is toxic to at least some class B strains. The nature of the genetic instability associated with the Pgl system was not detectable by Southern blot analysis. PMID- 8446037 TI - Reduced lipolysis of large apo E-poor very-low-density lipoprotein subfractions from type IV hypertriglyceridemic subjects in vitro and in vivo. AB - Heparin-Sepharose chromatography was used to separate Sf 60-400 very-low-density lipoproteins (VLDL) from type IV hypertriglyceridemic subjects into apolipoprotein (apo) E-poor and apo E-rich subfractions. Since we have previously demonstrated that the apo E-poor fraction accumulates in plasma of type IV subjects, the aim of the present studies was to determine whether it was resistant to lipolysis in comparison to the apo E-rich fraction. The apo E-rich fraction was found to be 30% more effective than the apo E-poor fraction at competing with a glycerol tri[1-14C]oleate emulsion for in vitro lipolysis by normolipidemic human post-heparin plasma (P < .01), when assayed under conditions in which both lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) were active. Similar results were obtained when bovine milk LPL was used as the source of lipolytic activity (P < .025 for apo E-rich relative to apo E-poor VLDL), while neither fraction competed effectively with the synthetic substrate for lipolysis by HTGL only. When equal amounts of triglyceride from VLDL subfractions were incubated with bovine milk LPL, 25% more free fatty acid was released from the apo E-rich fraction than from the apo E-poor fraction (P < .025). The effects of heparin-induced lipolysis in vivo in type IV subjects on the relative amounts and composition of these VLDL subfractions were also assessed. Heparin infusion was associated with a 50% reduction in plasma Sf 60 400 VLDL triglyceride concentration. In addition, heparin-induced lipolysis resulted in a marked decrease in the relative amount of apo E-rich VLDL, while the relative amount of apo E-poor VLDL was increased. These results demonstrate that the apo E-poor VLDL subfraction is resistant to lipolysis by LPL relative to its apo E-rich counterpart, suggesting that reduced lipolytic efficiency may contribute to its observed accumulation in plasma of type IV subjects. PMID- 8446036 TI - Glucagon-like peptide-I-(7-37) suppresses hyperglycemia in rats. AB - Glucagon-like peptide-(GLP) I-(7-37) is an endogenous hormone that has recently been demonstrated to be a potent insulin secretagogue. In these studies, GLP was administered during oral and intravenous (IV) glucose tolerance tests (OGTT and IVGTT, respectively) to determine whether this peptide could enhance postprandial insulin levels and thus reduce glycemic excursions. Surprisingly, during OGTT, GLP administration did not augment insulin secretion; however, GLP administration resulted in significantly lower glycemic excursions. In fasted rats, glycemic excursions were significantly reduced 10 and 20 minutes after receiving GLP (P < .001). Fed rats that received GLP had virtually no initial increase in plasma glucose level after administration of oral glucose. During IVGTT, glucose alone increased insulin levels eightfold, while administration of both glucose and GLP resulted in a 15-fold increase (P < .001). These IVGTT data support previous studies that show GLP to be a potent and glucose-dependent insulin secretagogue. Furthermore, all of these studies suggest that GLP reduces postprandial glycemic excursion and thus may be useful in the treatment of non-insulin-dependent diabetes mellitus. PMID- 8446038 TI - Relationship between serum sex hormones and the glucose-insulin-lipid defect in men with obesity. AB - It has been hypothesized that an alteration in the sex hormone milieu may underlie coronary heart disease (CHD) and its risk factors. Leading to this hypothesis and important to it was the observation that serum testosterone level correlated negatively and the estradiol to testosterone ratio (E/T) correlated positively with serum insulin and glucose levels in non-obese men. As a test of the validity of this observation, the present study was conducted to investigate these correlations in men with obesity. Obesity in men is associated with hyperestrogenemia, hypotestosteronemia, hyperinsulinemia, hyperglycemia, and CHD. To determine whether the relationships between sex hormone levels and insulin and glucose levels found in non-obese men also occur in obese men independent of obesity, fasting levels of these substances, as well as free testosterone (FT) and sex-hormone-binding globulin (SHBG), were measured in 55 obese men aged 21 to 70. Correlation coefficients of sex hormones with other risk factors for CHD, ie, cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), blood pressure, and waist to hip circumference ratio (W/H), were also calculated. As found previously, testosterone level correlated negatively with insulin (r = .31, P = .01) and glucose (r = -.23, P < .05) levels and the insulin to glucose ratio ([I/G] r = -.26, P < .05), and E/T correlated positively with insulin (r = .41, P = .001) and glucose (r = .24, P < .05) levels and I/G (r = .37, P < .005). The above correlations were controlled for body mass index (BMI) and age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446039 TI - The role of fatty acid saturation on plasma lipids, lipoproteins, and apolipoproteins: I. Effects of whole food diets high in cocoa butter, olive oil, soybean oil, dairy butter, and milk chocolate on the plasma lipids of young men. AB - The present studies were conducted to evaluate the cholesterolemic effects of whole-food diets high in stearic acid. In study no. 1, normocholesterolemic young men were fed diets high in stearic acid provided by cocoa butter (CB); oleic acid provided by olive oil (OO); linoleic acid provided by soybean oil (SO); and myristic acid (and lauric acid) provided by dairy butter (B). In study no. 2, different subjects with similar baseline characteristics were fed diets high in stearic acid provided by milk chocolate (C), CB, CB+B (4:1, MIX), and myristic (and lauric) acid provided by B. Both studies used a randomized, crossover, double-blind experimental design, and experimental subjects (n = 18 for study no. 1 and n = 15 for study no. 2) in each study consumed every diet for 26 days with a 1-month wash-out period between each experimental period. The diets provided 37% of calories from fat, of which 81% was provided by the test fat. Ten ounces (280 g) C was provided daily by the C diet. In study no. 1, the B diet was hypercholesterolemic, whereas the SO diet was hypocholesterolemic, compared with the other diets. The OO and SO diets were hypocholesterolemic compared with the CB diet. Low-density lipoprotein (LDL) cholesterol levels, in general, paralleled the changes in plasma total cholesterol levels. SO significantly decreased apolipoprotein (apo) B levels compared with the other diets. Plasma very-low density lipoprotein (VLDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and apo A-I levels were unaffected by the experimental diets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446040 TI - The role of fatty acid saturation on plasma lipids, lipoproteins, and apolipoproteins: II. The plasma total and low-density lipoprotein cholesterol response of individual fatty acids. AB - Regression analyses were performed on individual data from our two previous clinical investigations to establish the cholesterolemic effects of individual fatty acids. Our principal objective was to determine the effects of stearic acid on plasma total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol levels. Our second objective was to determine the variation in the cholesterolemic response of individuals to changes (delta) in the major dietary fatty acids. The best-fitting linear regression equations relating delta TC and delta LDL (mg/dL) were as follows: delta TC = 2.3 delta C14:0 + 3.0 delta C16:0 - 0.8 delta C18:0 - 1.0 delta polyunsaturated fatty acids (PUFA) and delta LDL = 2.6 delta C14:0 + 2.9 delta C16:0 - 0.5 delta C18:0 - 0.7 delta PUFA, where delta fatty acid = change in intake expressed as percent of calories. Based on these equations, in which stearic acid has a significant, negative regression coefficient, and the other regression models analyzed, it appears that stearic acid has an independent cholesterol-lowering effect. Using the equation we developed, 75% of the actual cholesterolemic responses were within +/- 10 mg/dL of the predicted response. In summary, we have developed a predictive equation (similar to those developed by both Keys and Hegsted) to estimate changes in plasma TC and LDL cholesterol levels of young men in response to changes in dietary fatty acids. However, our predictive equation separates stearic acid from the other long-chain saturated fatty acids (SFA) and indicates that it has an independent cholesterol-lowering effect. Thus, stearic acid is a unique long chain SFA because of its effect on plasma cholesterol level. PMID- 8446041 TI - The response of atrial natriuretic peptide to oral frusemide in patients with idiopathic urolithiasis. PMID- 8446042 TI - Insulin resistance in the conscious spontaneously hypertensive rat: euglycemic hyperinsulinemic clamp study. AB - To determine whether spontaneously hypertensive rats (SHR) are insulin resistant when compared with their genetic control, Wistar-Kyoto rats (WKY), insulin stimulated glucose utilization was studied in both strains with the euglycemic hyperinsulinemic clamp technique. This methodology can determine if insulin resistance is present and whether it is due to ineffective stimulation of peripheral glucose utilization, or to incomplete suppression of (hepatic) endogenous glucose production (EGP) by insulin, or both. Twelve WKY and 15 SHR (all male) had long-term catheters surgically placed. After surgical recovery, fasting metabolic parameters were measured in the conscious, unstressed state. Clamp studies were then performed on nine WKY and eight SHR. EGP was measured before and during euglycemic hyperinsulinemia with the tracer-dilution technique (6-3H-glucose). Indices of fasting metabolism (plasma glucose, insulin, and hepatic EGP) were not different between WKY and SHR. During the clamp studies, the glucose infusion rate (GIR) required to maintain euglycemia was significantly lower in SHR (SHR, 0.055 +/- 0.003 v WKY, 0.106 +/- 0.001 mmol/kg.min-1; P < .001). EGP was completely suppressed during euglycemic hyperinsulinemia in all WKY and in six of eight SHR. We conclude that conscious, nonstressed SHR are insulin resistant when compared with WKY. Attenuated insulin-stimulated peripheral glucose utilization implicates skeletal muscle, and not liver, as the primary site of insulin resistance in SHR. PMID- 8446043 TI - Lecithin-cholesterol acyltransferase and lipid transfer protein activities in liver disease. AB - The activities of lecithin-cholesterol acyltransferase (LCAT) and lipid transfer protein (LTP) were assayed using sensitive radioassay methods in controls (n = 113) and in patients with various liver diseases (n = 72). Plasma LCAT activity decreased with progression of hepatocellular damage. Plasma LTP activity in controls was 216 +/- 68 nmol/mL/h, and there were no significant differences between controls and patients with chronic hepatitis ([CH], 193 +/- 70), compensated liver cirrhosis (LC) with or without hepatocellular carcinoma ([HCC], 197 +/- 48 and 193 +/- 62, respectively), or decompensated liver cirrhosis ([dLC], 182 +/- 65). In acute viral hepatitis, LTP activity decreased significantly; however, the degree of reduction was not as dramatic as that for LCAT. There was no correlation between LCAT and LTP activity both in controls and patients with various liver diseases. LCAT activity was positively correlated with serum albumin (r = .52, P < 0.1) and cholinesterase (r = .37, P < .01) levels, and inversely correlated with serum bilirubin level (r = -.38, P < 0.1); there was no correlation between plasma LTP activity and these parameters of liver function. That plasma LTP activity did not change with hepatocellular damage may indicate that the liver in humans may not be the primary site of LTP production. PMID- 8446044 TI - Mechanisms of fasting hypoglycemia and concomitant insulin resistance in insulinoma patients. AB - To gain further insight into the pathogenesis of fasting hypoglycemia in patients with insulin-secreting adenoma of the pancreas, we studied seven patients affected by insulinoma (age, 42 +/- 7 years; body mass index [BMI], 27 +/- 2 kg/m2) and seven normal subjects. In insulinoma patients, hepatic glucose production (HGP) and glucose utilization (Rd) were evaluated by infusion of 3-3H glucose at spontaneous fasting plasma glucose concentration, after restoration of euglycemia and during euglycemic insulin clamp (40 mU/m2/min). In insulinoma patients, fasting plasma glucose concentration (2.8 +/- 0.2 v 4.5 +/- 0.1 mmol/L; P < .001), HGP, and glucose Rd (7.8 +/- 1.1 v 12.0 +/- 0.3 mumol/kg/min; P < .01) were lower than in normal subjects, while plasma insulin level was higher (138 +/ 19 v 38 +/- 3 pmol/L; P < .001). In insulinoma patients after attainment of euglycemia (4.7 +/- 0.2 mmol/L) by exogenous glucose infusion, insulin level increased slightly (174 +/- 18 pmol/L; P < .01) and glucose Rd was similar to that of normal individuals (12.8 +/- 0.6 v 12.0 +/- 0.3 mumol/kg/min). During the clamp studies, glucose Rd was lower in insulinoma patients (18.7 +/- 1.2 v 33.8 +/- 3.1 mumol/kg/min; P < .01) despite higher plasma insulin concentration (612 +/- 48 v 420 +/- 12 pmol/L). Therefore, glucose Rd/I x 100 ratio (where I is plasma insulin concentration) was much lower in insulinoma patients (3.1 +/- 0.9 v 8.0 +/- 0.7; P < .01), suggesting a marked degree of insulin resistance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446045 TI - Proinsulin and insulin concentrations following intravenous glucose challenges in normal, obese, and non-insulin-dependent diabetic subjects. AB - We investigated the effects of different intravenous (IV) glucose challenges on insulin and proinsulin secretion. On separate occasions, seven normal controls and five obese and five non-insulin-dependent diabetic (NIDDM) subjects each received an IV glucose tolerance test (IVGTT), a hyperglycemic clamp (HY), and a 60-minute, standardized, low-dose, continuous infusion of glucose (CIG) in a randomized fashion. Basal proinsulin concentrations in NIDDM subjects (8.4 +/- 5.0 pmol/L) were significantly higher compared with those of normal (1.1 +/- 0.2) and obese subjects (1.5 +/- 0.4; both P < .05). Basal molar proinsulin:insulin ratio (P:I) was also significantly higher in NIDDM subjects (22% +/- 12%) compared with normal (1.0%) and obese subjects (1.6% +/- 0.8%; both P < .01). Proinsulin concentrations did not increase significantly in any group during the first 10 minutes of the IV glucose challenges. However, during HY, significant increases in proinsulin concentration occurred after 60 minutes in each group. In normal and obese subjects, IV glucose administration resulted in significant acute increases in insulin concentrations compared with the characteristic blunted response in NIDDM subjects. The P:I ratio in normal and obese subjects did not change in the first 10 minutes after IV glucose administration. However, by the end of HY, the P:I ratio had increased significantly in normal subjects by 1% to 5% +/- 2% (P < .05), and in obese subjects by 1% to 5% +/- 1% (P < .02). In NIDDM subjects, both HY (19% +/- 10% to 27% +/- 12%) and IVGTT (18% +/- 9% to 43% +/- 16%) resulted in a transient increase in the basal P:I ratio by 5 minutes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446046 TI - Correlations of glycogen synthase and phosphorylase activities with glycogen concentration in human muscle biopsies. Evidence for a double-feedback mechanism regulating glycogen synthesis and breakdown. AB - The purpose of this study was to verify in man the relationships of muscle glycogen synthase and phosphorylase activities with glycogen concentration that were reported in animal studies. The upper level of glycogen concentration in muscle is known to be tightly controlled, and glycogen concentration was reported to have an inhibitory effect on synthase activity and a stimulatory effect on phosphorylase activity. Glycogen synthase and phosphorylase activity and glycogen concentration were measured in muscle biopsies in a group of nine normal subjects after stimulating an increase of their muscle glycogen concentration through either an intravenous glucose-insulin infusion to stimulate glycogen synthesis, or an Intralipid (Vitrum, Stockholm, Sweden) infusion in the basal state to inhibit glycogen mobilization by favoring lipid oxidation at the expense of glucose oxidation. Phosphorylase activity increased from 71.3 +/- 21.0 to 152.8 +/- 20.0 nmol/min/mg protein (P < .005) after the glucose-insulin infusion. Phosphorylase activity was positively correlated with glycogen concentration (P = .005 and P = .0001) after the glucose-insulin and Intralipid infusions, respectively. Insulin-stimulated glycogen synthase activity was significantly negatively correlated with glycogen concentration at the end of the Intralipid infusion (P < .005). In conclusion, by demonstrating a negative correlation of glycogen concentration with glycogen synthase and a positive correlation with phosphorylase, this study might confirm in man the double-feedback mechanism by which changes in glycogen concentration regulate glycogen synthase and phosphorylase activities. It suggests that this mechanism might play an important role in the regulation of glucose storage. PMID- 8446047 TI - Urinary excretion of polyamines in patients with surgical and accidental trauma: effect of total parenteral nutrition. AB - Excretion of polyamines first increases and then decreases in patients with multiple trauma receiving total parenteral nutrition (TPN). To separate the effects of trauma and TPN on polyamine excretion, we studied 12 patients with multiple trauma and 14 patients after surgery for colorectal malignancy. Patients were randomized to receive either TPN or hypocaloric glucose infusion. Urinary excretion of total and free polyamines, putrescine (PU), spermidine (SPD), and spermine (SP), and their metabolites, N1-acetylspermidine (N1-AcSPD) and N8 acetylspermidine (N8-AcSPD), and energy and nitrogen balance were measured. Polyamine excretion, excluding SP, markedly increased after trauma and surgery, exceeding the normal values by twofold to 10-fold. In patients receiving TPN, the excretion of total polyamines was 48% higher (P < .01), PU was 34% higher (P < .05), SPD was 35% higher (P < .05), and SP was 350% higher (P < .05) than in patients receiving hypocaloric glucose. Urinary excretion of SP was only 17% of the reference value during hypocaloric glucose (P < .05), but was normal during TPN. The difference in polyamine excretion between nutrition groups was more pronounced when normalized for nitrogen or energy balance. Patients receiving TPN were more hypermetabolic than patients receiving hypocaloric glucose (resting energy expenditure, 1.36 +/- 0.06 [SE] and 1.16 +/- 0.04 times predicted values, respectively; P < .025). Statistically, energy expenditure could explain the difference in polyamine excretion between nutrition groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446049 TI - Total energy expenditure in intravenously fed patients measured by the doubly labeled water technique. AB - The potential clinical use of the doubly labeled water (DLW) technique to measure total energy expenditure (TEE) in intravenously fed patients was assessed by applying the technique to 13 stable patients receiving total parenteral nutrition (TPN). TEE was compared with resting energy expenditure (REE), which was measured using a ventilated hood (n = 13), and with 24-hour energy expenditure (24h EE) measured in a whole-body calorimeter (n = 6). Daily measurements of urinary enrichment in 2H and 18O showed predominantly small and covariant fluctuations in elimination rates of these two tracers. The standard error of the estimate (SEFCO2) for the CO2 production rate (FCO2), which includes additional errors due to variability in isotopic fractionation, was calculated to be 2.65% +/- 0.70% of FCO2. TPN-related changes in background isotopic enrichment in subjects who were not dosed with isotope virtually ceased 10 days after starting intravenous feeding. TEE (4.99 +/- 1.10 kJ/min), TEE/REE (1.21 +/- 0.16 kJ/min), TEE/basal metabolic rate (]BMR] 1.31 +/- 0.16 kJ/min), and TEE (isotopic)/24h EE (calorimetric; 1.07 +/- 0.18 kJ/min) showed wide variability. This study provides some evidence for the validity of the DLW method in selected patients receiving TPN, since significant deviations from the assumptions of the method were not found in the subjects studied. The error associated with 2H sequestration during fatty acid synthesis is likely to be small, but could not be accurately measured. The contributions of activity and thermogenesis to TEE varied greatly, but overlapped with those reported in normal subjects. PMID- 8446048 TI - Effect of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor on triglyceride kinetics in chronically streptozotocin-diabetic rats. AB - The effect of simvastatin (MK-733, Banyu, Tokyo, Japan), a new inhibitor of 3 hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase on triglyceride kinetics, was studied in chronically streptozocin-diabetic rats. Diabetic rats, in whom diabetes was induced by a single intravenous injection of streptozotocin (40 mg/kg body weight) 2 months before the experiment, had significantly higher plasma glucose, triglyceride, and cholesterol levels compared with nondiabetic control rats, but triglyceride secretion rate was not increased. Both triglyceride secretion rate and plasma triglyceride level were significantly suppressed under nonfasting conditions in diabetic rats fed a (0.1%) simvastatin containing diet for 10 days. After an overnight fast, their triglyceride secretion rate was not suppressed by this diet. However, their plasma triglyceride level was significantly (50%) suppressed, suggesting improved triglyceride removal from the circulation. In diabetic rats, the newly secreted triglyceride-rich lipoprotein particles were significantly cholesterol-enriched, but simvastatin had no effect on their lipid composition. These results suggest that the hypertriglyceridemia seen in chronically diabetic rats is mainly due to a triglyceride-removal defect, and that simvastatin reduces plasma triglyceride levels in these rats both by stimulating triglyceride removal and by reducing its entry into the circulation. PMID- 8446050 TI - Partial 3 beta-hydroxysteroid dehydrogenase deficiency presenting as new-onset gynecomastia in a eugonadal adult male. AB - The postpubertal clinical presentation of 3 beta-hydroxysteroid dehydrogenase deficiency (3B-HSD deficiency) is less well-defined for adult males than for adult females, who often present with hirsutism. We describe a male with normal puberty who presented with new-onset gynecomastia at age 24. Common causes of gynecomastia were excluded. Dehydroepiandrosterone-sulfate (DHEA-S), estradiol, estrone, and 24-hour urinary 17-ketosteroid levels were elevated. A feminizing tumor was considered; biochemical tumor markers, chest x-ray, ultrasound of testes, and abdominal computed tomography (CT) scan were negative. Dexamethasone suppression testing showed normal suppression of 24-hour urinary adrenal steroids. Cosyntropin-stimulation testing showed normal cortisol, 11 deoxycortisol, 17-OH progesterone (17-OHP), and aldosterone levels, but significant elevations of pregnenolone (preg), 17-OH preg, progesterone, DHEA, and androstenedione (A) levels. The sperm count was high and gonadotropin releasing hormone (GnRH)-stimulation testing showed a normal increase in testosterone (T) level, suggesting that the defect did not involve the testes. It is concluded that this patient's gynecomastia is due to 3B-HSD deficiency with an associated alteration in sex hormone ratios. To our knowledge, this is the first well-described adult male with normal gonadal function presenting with postpubertal gynecomastia due to 3B-HSD deficiency. This defect may be a frequently unrecognized cause of gynecomastia. PMID- 8446051 TI - Osteoporosis and increased bone fractures in cerebrotendinous xanthomatosis. AB - Significant osteoporosis determined by skeleton radiography and bone densitometry was found in 15 patients with cerebrotendinous xanthomatosis (CTX) whose mean age was 31 +/- 11 years. In three CTX patients, bone biopsies confirmed osteoporosis. Nine patients also sustained bone fractures following minimal trauma. Serum 25 hydroxyvitamin D ([25-OHD] 14.6 +/- 6.6 ng/mL v [normal] 30.4 +/- 8.0 ng/mL; P < .001) and 24,25-dihydroxyvitamin D ([24,25(OH)2D] 1.2 +/- 0.4 ng/mL v [normal] 2.7 +/- 0.8 ng/mL; P < .001) levels were low. Serum concentrations of 1,25(OH)2D, calcium, inorganic phosphorus, alkaline phosphatase, parathyroid hormone, and calcitonin were normal. Patients showed classic manifestations of CTX, including dementia, pyramidal and cerebellar insufficiency, peripheral neuropathy, cataracts, and tendon xanthomas associated with elevated serum cholestanol concentrations. These results demonstrate that extensive osteoporosis and increased risk of bone fractures are components of this inherited disease. PMID- 8446052 TI - Low-density lipoprotein cholesterol responsiveness to diet in normolipidemic subjects. AB - Both apolipoprotein E genotype (apo E) and diet predict very-low-density (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) levels. In a retrospective pooled analysis of six studies, we sought to identify the predictors of VLDL-C and LDL-C change, or "responsiveness," to a diet crossover. "Response" to diet was studied in 67 normolipidemic subjects of common apo E genotype. Subjects were fed two contrasting, metabolically controlled diets: one had a low polyunsaturated to saturated fatty acid ratio (P:S), and the other had a high P:S ratio. Multiple blood samples were analyzed for VLDL-C and LDL-C levels at the end of each metabolic diet period, and values were averaged and differences were calculated. Despite adjustment for significant predictors across the component studies, a wide range of LDL-C responsiveness was found, with an average decrease of 28 mg/dL. Multivariate regression analysis was used to identify the most significant predictors of LDL-C response to the diet crossover. All dietary and clinical variables were entered by stepwise regression for potential inclusion in a "best fit" model. The degree of change in saturated fat content and age were the most significant predictors of LDL-C responsiveness. Neither dietary cholesterol nor apo E phenotype were significant predictors of responsiveness. The most LDL-C responsive subjects were older and required smaller reductions in dietary saturated fat levels than did less-responsive subjects to achieve a comparable reduction in LDL-C levels. Multiple regression analysis suggested a precursor product relationship between VLDL-C and LDL-C responsiveness. PMID- 8446053 TI - Antihypertensive effects of CS-045 treatment in obese Zucker rats. AB - The association of hypertension with obesity has been well recognized, but the etiology remains poorly understood. Obesity is characterized by hyperinsulinemia, which reflects peripheral insulin resistance. Insulin resistance may participate in the development of hypertension with obesity. CS-045 [(I)-5-[4-(5-hydroxy 2,5,7,8-tetramethylchroman-2-yl-methoxy)be nzy l]-2,4- thiazolidiendion] is a new orally effective antidiabetic agent that potentiates insulin action and reduces insulin resistance in obese Zucker rats and other obese diabetic animals. In this study, we examined the antihypertensive effect of CS-045 in obese male and female Zucker rats as a model of hypertension associated with obesity. CS-045 was administered as a food admixture (approximately 16 and approximately 70 mg/kg/d) for 4 weeks (female) and (approximately 15 and approximately 67 mg/kg/d) 8 weeks (male) in obese Zucker rats at 5 to 7 months of age. CS-045 slightly but significantly decreased plasma glucose levels. Plasma insulin levels were significantly decreased in obese male rats, but were not significantly decreased in obese female rats. Drug administration led to significant decreases in plasma triglyceride and cholesterol levels and systolic blood pressure (SBP) in a dose dependent manner from 1 week after administration in obese Zucker rats. CS-045 increased urinary sodium excretion, sodium/potassium ratio, and creatine clearance in a dose-dependent manner, and also led to a remarkable decrease in urinary protein excretion. However, CS-045 did not reduce urinary catecholamine excretion. These data indicate that CS-045 may promote renal sodium excretion and improve decreased glomerular filtration rates, which may reflect the amelioration of insulin resistance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446054 TI - Effect of fish oil on glucose metabolism in the interleukin-1 alpha-treated rat. AB - Fish oil has been demonstrated to ameliorate many of the responses to infection. This study was conducted to determine whether fish oil feeding could modify the alterations of glucose metabolism induced by interleukin-1 alpha (IL-1 alpha) infusion in the rat. Male Sprague-Dawley rats were pair-fed for 5 weeks on two experimental diets in which the source of fat was either fish oil or soybean oil and provided 20% of calories; the diets were isonitrogenous and isocaloric. After 5 weeks of feeding, rats from both diet regimens were further divided into two subgroups to receive a 3-hour infusion of either 0.1% albumin in saline or 0.1% albumin in saline containing IL-1 alpha. A total of 20 micrograms/kg IL-1 alpha was administered, and half the dose of IL-1 alpha was given as a bolus and the remaining portion (10 micrograms/kg) was continuously infused into the jugular vein. During the last 2 hours of IL-1 alpha infusion, a primed constant infusion of D-(6-3H)glucose and D-(U-14C)glucose was combined to determine the effects of IL-1 alpha and diet on glucose kinetics. Plasma levels of glucose and insulin, energy expenditure, and respiratory quotient were also measured. IL-1 alpha significantly increased concentrations of plasma insulin and the percentage of glucose carbon recycling, confirming previous findings. Concentrations of glucose and insulin with IL-1 alpha treatment were significantly higher in soybean oil- fed animals compared with fish oil-fed animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446055 TI - Effect of hyperglycemia per se on glucose turnover rates in patients with insulin dependent diabetes. AB - The effect of hyperglycemia, per se, on glucose utilization and hepatic glucose production was reevaluated in eight C-peptide-negative insulin-dependent diabetic patients using primed-continuous noncontaminated 3-3H-glucose infusion and labeled glucose infusates. The night before study, euglycemia was maintained by a variable insulin infusion. During the studies, insulin was infused at basal replacement rates determined as the rate required to maintain euglycemia in the morning. After a 2-hour equilibration period, either plasma glucose level was increased to 12 mmol/L for 4 hours using a variable glucose infusion, or no glucose was infused (control day). On the hyperglycemic day, glucose utilization increased 16% (86 +/- 2 to 99 +/- 4 mg.m-2.min-1, P < .02) and glucose production decreased 45% (85 +/- 3 to 47 +/- 4 mg.m-2.min-1, P < .01). On the control day, both glucose utilization and glucose production decreased (84 +/- 3 to 68 +/- 3 and 84 +/- 3 to 65 +/- 3 mg.m-2.min-1, respectively; both P < .01). Therefore, comparing rates at the end of the hyperglycemic and control studies, glucose utilization was increased by 45% and glucose production was decreased by 28% in response to hyperglycemia (both P < .01). Thus hyperglycemia, at basal insulin levels enhanced glucose utilization and suppressed glucose production in insulin dependent diabetic patients. Quantitatively, the enhancement of glucose utilization was more important than the suppressive effect on glucose production. PMID- 8446056 TI - Cosecretion of atrial and brain natriuretic peptides stimulated by endothelin-1 from cultured rat atrial and ventricular cardiocytes. AB - We examined the secretion of immunoreactive (ir) atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in primary cultures of atrial and ventricular cardiocytes from neonatal rats, and also investigated the stimulatory effect of endothelin-1 (ET-1) on ir-ANP and ir-BNP release from these cells. After 2 days of culture, rat atrial and ventricular cardiocytes secreted both ir-ANP and ir BNP into serum-free medium in a time-dependent manner. The amount of ir-BNP released per 10(5) ventricular cells was approximately 60% to 70% (1.8 +/- 0.5 pg/h, 2.5 +/- 0.4 pg/2 h, 2.6 +/- 0.4 pg/4 h) of that released from atrial cells (2.8 +/- 0.4 pg/h, 3.5 +/- 0.6 pg/2 h, 4.6 +/- 0.6 pg/4 h), although ir-ANP was secreted almost entirely from atrial cells. ET-1 clearly stimulated secretion of both ir-ANP and ir-BNP in atrial and ventricular cardiocytes. These observations indicate that ir-BNP is cosecreted with ir-ANP not only from atrial cardiocytes, but also from ventricular cardiocytes in the rat, and that ET-1 stimulates the secretion of these natriuretic peptides by a direct mechanism, not through a hemodynamic change. PMID- 8446057 TI - [Biosensors in biotechnology and medicine]. AB - The work is a review of the state-of-art of research in the field of biological sensors. The enzymatic and immune biosensors are described. Problems concerning application of microorganisms as biosensors have been reported in detail. The use of luminescent bacteria and luciferase sensors is under discussion. The principles of operation of fibrous-optic and semiconducting biosensors are stated. PMID- 8446058 TI - [The isolation and purification of a nonspecific DNAse from Mycoplasma fermentans PG-18]. AB - Nonspecific endogenic DNAase has been isolated from biomass of Mycoplasma fermentans PG-18 cells and purified to the homogeneous state. The scheme of isolation consists of purification stages on columns with phosphocellulose, DNA cepharose CL-8B and phenylcepharose. DNAase was not bound to phosphocellulose, its volume was equal to zero. Then this DNAase was passed through column with DEA cepharose CL-6B (elution by gradient KCl from 0.1 to 1.8M): enzyme was eluted at KCl concentration in the eluting buffer from 0.1 to 1.2 M. The enzyme was purified to the homogeneous state on column with phenylcepharose (elution by linear gradient of ethylene glycol from 30 to 80%): enzyme was eluted at the concentration of ethylene glycol in the eluting buffer from 43 to 80%. According to data obtained using gel-electrophoresis, under the denaturing conditions molecular mass of enzyme in acrylamide gel was 34 kDa. PMID- 8446059 TI - [The effect of trace elements on the morphogenesis of fungal species in the genus Fusarium Lk:Fr]. PMID- 8446060 TI - Alternation of exo- and endotrophy during the mitotic cycle of the yeast cells. AB - The utilization of the intracellular and extracellular sources of carbon and energy during the mitotic cycle of yeasts Saccharomyces cerevisiae, Kluyveromyces marxianus, Candida boidinii, Candida tropicalis has been studied. Increase in the consumption rate of carbon and energy sources and in the exogenous respiration rate at G1- and G2-phases of the mitotic cycle is shown. The rate of the endogenous respiration of the cells at these phases decreased. The hypothesis has been proposed that during the mitotic cycle of the yeast cell the regular alternation of exotrophy (the utilization of the extracellular carbon and energy sources by a cell) and endotrophy (the process of the utilization of the intracellular carbon and energy sources by a cell) occurs. It is possible to reveal the exotrophic cells by the cytological method which is based on the calculation of dead cells after incubation of the yeast suspension in amyl alcohol solution. This method has revealed that exotrophic and endotrophic processes do not predominate one over another but alternate at the mitotic cycle. Exotrophy and endotrophy are phase-specific processes. The G1- and G2-phases are exotrophic processes, phases S and M are endotrophic ones. PMID- 8446061 TI - [Vibrio albensis phages]. AB - Vibrio albensis phages have been found for the first time. Lysogenic strains of the luminescent vibrios are shown to be producers of moderate phages. The vibrios are attributed to the 1st morphological group according to A. S. Tikhonenko's classification. The studied phages are an independent serological type and have no antigenic affinity to cholera phages. PMID- 8446062 TI - [The glycolipid composition of Francisella tularensis strains with different degrees of attenuation]. AB - The glycolipid composition of F. tularensis strains was investigated by silica gel thin-layer chromatography. Vaccine strains in contrast to virulent ones lacked glycolipid 8, possessed new glycolipid 8-a and a higher level of glycolipid 7. Low immunogenic strains had a decreased content of glycolipids, while avirulent non-immunogenic strain (15-a) nearly completely lost them. Thus, the glycolipid composition is associated with the level of attenuation, virulence and immunogenicity of F. tularensis. PMID- 8446063 TI - [A method for determining the content of anionogenic surface-active peptidolipids of bacterial origin]. AB - The simple and selective method of anionic biosurfactant concentration determination in bacterial cultural broth is offered. The method is based on the ability of the anionic surfactants to form some coloured complex with the cationic indicator methylene blue registered by spectrophotometer. The suggested method is recommended for the study of biosynthesis of microbial surfactants. PMID- 8446064 TI - Initial medical reception, intervention and survey work in combined military and civilian humanitarian aid: operation 'Safe Haven', northern Iraq 1991. AB - Service medical teams were involved in the medical screening and initial reception of displaced Kurds into the first United Nations Relocation Camp in Zakho, Northern Iraq in April 1991. Massive logistic support and adequate security were required for the delivery of the essential elements of relief. The prompt deployment of such teams enabled rapid surveys of the medical extent of the disaster to be undertaken during the screening process whilst individuals were prioritized for rehydration, supplement feeding and therapy. Over 12,000 displaced persons entered the camp in the first 10 days. Reported perinatal mortality during the two-month exodus crisis in an unselected group of 2,200 was 375 per 1,000 births. In the same group of families surviving to tell the tale, one in five of the infants who had been in the mountains had died and the fertility rate may have been as high as 380 per 1,000 women of child-bearing age in the previous year. In a larger survey of 3,825 unselected persons entering the camp, 745 (19.5 per cent) were estimated to be under five years of age and a quarter of these had a significant medical problem. There were 290 (7.6 per cent) estimated to be under two, and a quarter of these were judged to be severely malnourished. A high degree of international cooperation between military and civilian medical and relief teams was demonstrated in dealing with this crisis. PMID- 8446065 TI - View of a war from a pathology department: Croatian experience. AB - This report presents an analysis of autopsy records from the Department of Pathology and Forensic Medicine, Osijek General Hospital, in the period from 2 May 1991, when 12 Croatian policemen were killed in an ambush in Borovo Selo and the war against Croatia unofficially began, until 15 January 1992, when the last cease-fire agreement between Croatia and Serbia, sponsored by the United Nations, became effective. During that time, 651 war-related autopsies were performed, constituting 42 per cent of all the deaths recorded in eastern Slavonia for that period. This number presents an 11-fold increase in the number of violent deaths in comparison to the same period of the pre-war year 1989 to 90. Forty-four per cent of all deaths were civilian ones. Explosive wounds were the most frequent cause of death: they accounted for 60 per cent of the civilian and 49 per cent of all the deaths. This fact and the extensive destruction of the cities in eastern Slavonia, including their hospitals, indicate that a principal characteristic of this and many modern wars is sudden and unexpected ground and air attacks on civilian targets. PMID- 8446066 TI - Acute cardiac effects of 'SCUD' missile attacks on a civilian population. AB - The 'SCUD' raids on Israel during the Gulf War afforded a rare opportunity to examine the effect of mass acute fear on the cardiac health of the general population. Press reports suggested an alarming rise in cardiac deaths during the first missile raids. In order to ascertain this statement, we examined the Emergency Room records of a community hospital in the affected area and all the death certificates in the local region. The periods studied were from 1 January to 28 February 1991, and the equivalent weeks in 1990. The Emergency Room records showed that there was an increased rate of cardiac complaints throughout the war, most marked during the first week. However, this was not accompanied by an increased cardiac mortality, either in the hospital or in the region as a whole, except during the first week. A similar increase in cardiac mortality occurred during the same week the previous year. The increased incidence of acute cardiac events during the first week of the war was probably a coincidence, and not a direct consequence of mass fear. Panic, occasioned by press reports, may have led to a lower threshold of referral which persisted throughout the war. PMID- 8446067 TI - Cardiovascular complaints following the uprising of December 1989 in Romania. AB - The cardiovascular system may react to stress either by coronary events, such as angina pectoris or myocardial infarction, or by non-coronary responses, such as rises in blood pressure or non-specific circulatory disorders and chest pain. There is contradictory information about the cardiovascular reactions to war stress. The aim of this study was to investigate the effects of stress produced by the uprising of December 1989 in Romania on the cardiovascular system. Cases referred from 21 to 31 December 1989 to the emergency department of the largest university clinic of the Cluj district, and those admitted there, were analysed and compared with cases referred in the same periods in 1988, 1990 and 1991 and from 1 to 10 January 1990. There was a significant increase in non-coronary cardiovascular complaints referred for consultation in the first 10 days from the beginning of the uprising in Cluj and a non-significant increase in the following 10 days, but no increase in consultations for complaints of coronary origin due to unstable angina and acute myocardial infarction or changes in hospital admissions. In conclusion, the stress produced by the uprising in Romania was correlated with a higher incidence of non-coronary cardiovascular complaints but no alteration in coronary events (unstable angina, acute myocardial infarction), or in hospital admissions for cardiovascular complaints. PMID- 8446068 TI - Post-traumatic stress in children. PMID- 8446069 TI - Medical mediation. PMID- 8446070 TI - Autoimmune hypothesis in narcolepsy. AB - Since the discovery of an almost 100% association of HLA-DR2 with narcolepsy cataplexy, many efforts have been made to demonstrate the intervention of immune factors in the pathogeny of the disease. Some epidemiological features could support this hypothesis: age of onset around 25, triggering factors, association with multiple sclerosis. Molecular studies at the DNA level have, up to now, failed to uncover an abnormal gene in the HLA system, which would imply that the DR2 antigen acts through its role in the immune response. However, results have been largely inconclusive as far as classical features of autoimmunity in blood and CSF are concerned. In canine narcolepsy, a linkage with a human immunoglobulin-related gene has recently been shown, and may constitute a counterpart of the HLA association in man. Thus, the hypothesis of a transient and discrete autoimmune aggression may be ruled out. PMID- 8446071 TI - Daytime somnolence: therapeutic approaches. AB - Excessive daytime somnolence is a major neurological problem involving about 4% of the general population. Its treatment is based on accurate etiological dissection. Sleep-disordered breathing is a major cause of EDS. Stimulant medication is helpful in many other instances. PMID- 8446072 TI - "Somnolence: its importance in society". PMID- 8446073 TI - [Alcohol, sleep and biological rhythms]. AB - Alcohol reduces sleep latency but notably alters sleep structure: sleep is fragmented, particularly at the end of the night. Slow wave sleep duration is enhanced in the first part of the night and REM sleep duration and density are diminished. Alcohol withdrawal provokes inverse effects in alcoholic patients: sleep onset is delayed, slow wave sleep durations diminished and REM sleep duration is enhanced. REM sleep is associated with motor inhibition failure. Sleep remains disturbed in long term evaluations. Alcohol promotes the occurrence of sleep apneas and hypopneas. This effect persists in alcoholics after alcohol withdrawal. Sleep disturbances in alcoholism can be partly understood as the expression of amplitude diminution and phase advance of biological rhythms. Thus, the chronobiologic characteristics of alcoholics resemble those of depressives or the elderly. PMID- 8446074 TI - Daytime sleepiness in epileptic patients on long-term monotherapy: MSLT, clinical and psychometric assessment. AB - A multiparametric investigation of daytime sleepiness was carried out in 10 patients with a generalized epilepsy treated by phenobarbital, 10 with a cryptogenic partial epilepsy treated by carbamazepine and 10 healthy controls. After a standard ambulatory night-time polysomnography, an objective and subjective estimate of daytime sleepiness was made in each subject by means of the Multiple Sleep Latency Test (MSLT) and visual analogue rating scale (VARS), respectively. Furthermore, a parallel assessment of mood and cognitive tasks involving attention and psychomotor speed was also carried out. The data show that patients on chronic treatment with phenobarbital have a greater daytime sleep tendency and they show a worse score at the digit symbol substitution test, than patients on carbamazepine and healthy controls. PMID- 8446075 TI - [Sleepiness and sleep apnea syndrome. Analysis of 188 questionnaires (102 patients and 86 controls)]. AB - A questionnaire was given to 102 obstructive sleep apnea patients and 86 controls. A somnolence index was defined by averaging the scores of the answers to eleven questions concerning sleepiness. This index separated patients and controls (P < 0.0001). It was correlated with the apnea + hypopnea index (r = 0.32, P < 0.001), the body mass index (r = 0.45, P < 0.001) and with an objective measurement of sleepiness obtained from a modified multiple sleep latency test (r = -0.54, P < 0.001). Depending upon the current occupation, the tendency to fall asleep decreased in the following order: watching TV, passenger in a means of transport, reading, attending a show, attending a meeting, driving a car, and eating. This order is the same in patients and controls, irrespective of their "overall sleepiness". Thus, the circumstances of falling asleep are indicative of the severity of sleepiness. PMID- 8446076 TI - [Sleep deprivation and exercise tolerance in hot weather]. PMID- 8446077 TI - Evaluation of excessive daytime sleepiness. AB - Measures for assessing daytime sleepiness can be categorized into four general types-behavioral observation, laboratory performance, introspection, and physiological techniques. Each approach has its advantages and disadvantages. Thus, for example, observational techniques may provide a minimally 'contaminated' sample, but inferences may be quite difficult; laboratory performance measures may indicate vulnerabilities associated with sleepiness, but may be limited because of practice effects; introspection provides a personal perspective, but that point of view may be influenced by past history or ability to articulate; physiological measures may provide the most 'objective measures', but are difficult to apply to field studies. The Multiple Sleep Latency Test (MSLT) is the most thoroughly studied physiological measure of sleepiness relying upon serial assessments of the speed of falling asleep in standard conditions intended to optimize the sleep onset process. Procedures for administering, analyzing, and interpreting the MSLT are presented. PMID- 8446078 TI - Congenital diaphragmatic hernia. Part II. AB - The infant with a congenital diaphragmatic hernia presents many challenges to those caring for him. A thorough understanding of both anatomic and physiologic components can enable the caregiver to accurately assess the patient and employ interventions which will minimize complications. Part I of this article discussed the incidence, mortality, embryology, diagnosis, pathophysiology, and conventional management. This article discusses alternatives to conventional management, outcome predictors, current research and follow-up of the infant with congenital diaphragmatic hernia. Recent advances in the use of non-conventional treatment, especially ECMO, for infants with diaphragmatic hernias have proven successful. Infants having risk factors associated with 100 percent mortality prior to the advent of ECMO are now surviving. In addition to ECMO, pharmacologic therapy, fetal surgery, lobar transplant, and ventilatory management research show promising results for treatment of the infant with a congenital diaphragmatic hernia. PMID- 8446079 TI - Implementation of a quiet hour: effect on noise levels and infant sleep states. AB - It is necessary to decrease environmental stimuli in order to provide developmentally supportive care to the very low birthweight (VLBW) infant, thereby enhancing the sleep/wake cycle and possibly physiologic stability. The purpose of this study was to determine if it was possible to decrease the noise level in the Developmental Unit, and promote sleep states in infants on the unit. After determining control noise levels and infant state, the last hour of each shift was designated a Quiet Hour. During this time, noise levels were monitored in the room in five locations. Infant sleep states were also noted. The results indicate that noise levels decreased significantly on two of the three shifts. Fewer infants were crying during the Quiet Hour than the control period (2.4 vs 14.3 percent), and more were in deep or light sleep (84.5 vs 33.9 percent). This study demonstrates that noise levels in Developmental Units can be significantly decreased, and that the decreased noise levels positively impact infant state. By enhancing sleep states, nurses can enhance the long term developmental outcome of the VLBW infant. However, the reduction of noise is highly dependent on the collaborative efforts of all health care providers within the unit. PMID- 8446080 TI - The critical times: meeting parental communication needs throughout the NICU experience. AB - The parental stresses caused by a premature birth and the NICU experience may create problems in the parent-child relationship. These problems may lead to subsequent difficulty in bonding or parenting, and may even be related to child neglect and abuse. The NICU staff is in a unique position to help minimize parental stress by providing information, support, and understanding to facilitate coping with fear and uncertainty. Parents need help in adjusting their expectations to reality, especially during the early days in the NICU. While the mother is still hospitalized, the father is in an especially vulnerable position, as he may be unprepared to be a primary caregiver, threatened by the female staff, and expected to assume a focal role while he may need comfort himself. Information that is most helpful to parents is that which helps return some control to them. Involving parents in the child's caregiving and in decision making also helps increase parental feelings of control and decrease feelings of stress. Attention should be paid to the questions and nonverbal communication of the parents to ascertain when communication is especially important. Key times during which communication is typically crucial are identified. PMID- 8446081 TI - Music therapy: fertile ground for application of research in practice. AB - When participating in research studies in the clinical setting it is important to remember the goals of the interventions under study. Frequently the parameters and design of the research, while necessary to validate findings, are not written in stone for future application. It is possible to consider other situations in which the intervention might be applied that lie outside the current research protocols. To fully utilize research findings, apply them to your own unique practice and then set up your own study using the original work as a starting place. PMID- 8446082 TI - Neonatal pain. PMID- 8446083 TI - Evaluation of two endotracheal suction regimes. PMID- 8446084 TI - Instruments in neonatal research: measurement of temperature. PMID- 8446085 TI - How to evaluate lung fields on the neonatal chest X-ray film. AB - The general principles of evaluating lung fields have been presented. These concepts will be applied in future columns as specific disease entities are discussed. Before the column focuses on the specific cardiopulmonary pathologies, however, there will be one more column addressing general principles. Evaluation of cardiac size will be covered in the next column. PMID- 8446086 TI - Teaching families from diverse cultural backgrounds. PMID- 8446087 TI - Amniotic band syndrome: a nursing perspective. AB - Amniotic band syndrome is a disease process that is unfamiliar to many neonatal nurses. It's presentation is variable in both type and severity, and pathophysiology and etiology still mystify those who have studied it in depth. Although better understood today, there remain many unanswered questions. A review of the current literature revealed an abundant supply of medically-based information and also a lack of resources focused on nursing-oriented information. This paper addresses the nursing implications of caring for an infant with amniotic band syndrome. A knowledgeable nurse will be able to assist in the diagnosis of amniotic band syndrome and have a better understanding of how to care for both the infant and his family. Both nursing and medical research needs to continue in this area to gain more knowledge about this complex disease process. PMID- 8446088 TI - Health care cost: where to begin. PMID- 8446089 TI - Patterns of obesity in Missouri. AB - Obesity is a major preventable health problem in Missouri and in the nation. Using survey data, we examined the prevalence of obesity in population subgroups and the overall trend. Prevalence of obesity was higher among blacks, middle-aged persons, and persons with less education or lower family income. Without additional attention, Missouri is unlikely to achieve the year 2000 objective of < or = 20% prevalence of obesity. PMID- 8446090 TI - Indications for prophylactic mastectomy. AB - This article reviews the current state of knowledge regarding factors which put women at highest risk for developing breast cancer and identifies that population we consider as potential candidates for prophylactic mastectomy. Specifically, we focus on the concept of cumulative predisposition and the relative risk assigned to more significant factors that increase a woman's chances of developing breast cancer: family history, proliferative breast histology, and previous cancer in one breast. In addition to outlining the results of reconstruction, the article also examines the controversy surrounding the issue of whether any mastectomy can be truly prophylactic. We conclude with advice to physicians who must counsel women concerned about their breast cancer risk so they can help their patients make fully informed choices. PMID- 8446091 TI - Update: influenza activity--United States and worldwide, and composition of the 1993-94 influenza vaccine. AB - In collaboration with the World Health Organization (WHO) international collaborating laboratories and with state and local health departments in the United States, CDC conducts surveillance to monitor influenza activity and to detect antigenic changes in the circulating strains of influenza viruses. This report summarizes surveillance for influenza in the United States and worldwide during the 1992-93 season and describes the composition of the 1993-94 influenza vaccine. PMID- 8446092 TI - Malaria in Montagnard refugees--North Carolina, 1992. AB - Refugee groups emigrating from some areas of the world may have increased prevalences of exotic and potentially life-threatening diseases, challenging the diagnostic and case-management capacities of local and state health departments. This report summarizes efforts by public health officials and clinical health care providers to diagnose and manage cases of malaria among a group of 402 Montagnard refugees who resettled to three counties in North Carolina in November 1992. PMID- 8446093 TI - Inability of retroviral tests to identify persons with chronic fatigue syndrome, 1992. AB - Chronic fatigue syndrome (CFS) is characterized by prolonged, debilitating fatigue. Although the cause of CFS unknown, CDC and researchers in other organizations have been investigating whether infection with a previously unidentified retrovirus might be an etiologic factor. Based on reports suggesting that retroviral infection with a human T-lymphotropic virus type 2 (HTLV-II)-like retrovirus or a spumavirus might be associated with CFS, some research and commercial laboratories developed assays to test specimens from persons with CFS. Even though the hypothesized association between infection with retroviruses and CFS has not been confirmed, these tests are used commonly to evaluate patients with CFS. This report summarizes the findings of a controlled, blinded study conducted in 1992 to determine whether three retroviral tests can distinguish serologically between patients with CFS (i.e., case-patients) and healthy controls. PMID- 8446094 TI - Public health focus: prevention of blindness associated with diabetic retinopathy. AB - Each year in the United States, as many as 40,000 new cases of blindness occur among persons with diabetes (CDC, unpublished data, 1993). Diabetes is the leading cause of new blindness among U.S. adults aged 20-74 years. In addition, persons with diabetes are 25 times more likely than the general population to become blind. Most of this blindness in persons with diabetes results from diabetic retinopathy, a disorder characterized by microvascular changes and hemorrhage in the retina. Seven million persons in the United States have diabetes, and diabetic retinopathy will affect the majority during their lifetimes. This report summarizes information regarding the efficacy, effectiveness, and cost-effectiveness of screening for diabetic retinopathy. PMID- 8446095 TI - Pertussis outbreaks--Massachusetts and Maryland, 1992. AB - During November 1992, cases of pertussis among students in Massachusetts and Maryland were reported to the respective state health departments. This report summarizes the investigation of and approaches to controlling these outbreaks. PMID- 8446096 TI - Fireworks-related injuries during the new year period--Naples, 1992-93. AB - Celebrating the new year with fireworks is traditional in Italy. A national surveillance system maintained by police indicated that on New Year's Eve 1992, more than 1100 fireworks-related injuries and four deaths occurred in Italy (Ministry of the Interior, unpublished data, 1993). In many areas of the country, the use of fireworks begins several weeks before the new year and continues through the Epiphany (January 6). To characterize fireworks-related injuries in the province of Naples--an area that contains less than 6% of the total population of Italy but accounts for 15% of the reported fireworks-related injuries in the country--the Regional Health Observatory of Campania and the Italian field epidemiology training program implemented an active surveillance system in each of the 18 public emergency rooms (ERs) in the province (1992 population: 3.5 million). This report summarizes surveillance results for the new year period 1992-93. PMID- 8446097 TI - Bicycle helmet promotion programs--Canada, Australia, and United States. AB - The use of bicycle helmets substantially reduces the risk for serious head injuries during bicycle-related crashes. Despite this benefit, epidemiologic data indicate a worldwide low prevalence of helmet use. Strategies to increase the use of bicycle helmets in the United States and other countries include subsidies, legislation, and education. This report summarizes information regarding three strategies to increase bicycle helmet use and the impact of implementing these approaches in Canada (helmet subsidies), Australia (legislation), and the United States (education). PMID- 8446098 TI - Quarterly table reporting alcohol involvement in fatal motor-vehicle crashes. PMID- 8446099 TI - Infant mortality--United States, 1990. AB - The infant mortality rate for the United States for 1990-9.2 infant deaths per 1000 live births--was the lowest rate ever recorded and represented a decrease of 6% from the rate of 9.8 for 1989. This report summarizes 1990 infant mortality data based on information from birth and death certificates compiled by CDC's National Center for Health Statistics' (NCHS) Vital Statistics System and compares findings with those for 1989. PMID- 8446100 TI - State activities for prevention of lead poisoning among children--United States, 1992. AB - In 1990, an estimated 3 million children aged < 6 years had blood lead levels (BLLs) > 10 micrograms/dL--levels associated with decreased intellectual performance and other adverse health events. During October 1991, CDC revised its childhood lead poisoning prevention policy statement; the recommendations included lowering the BLL of concern from 25 micrograms/dL to 10 micrograms/dL. To characterize efforts of state health agencies in lead-poisoning prevention and to assess the extent of implementation of the recommendations in the 1991 lead statement, in June 1992, the Lead Task Force of the Association of State and Territorial Health Officials (ASTHO) conducted a questionnaire survey of directors of public health in each of the 50 states. This report summarizes findings of the survey regarding screening issues, funding mechanisms, and follow up of children with elevated BLLs. PMID- 8446101 TI - False-positive serologic tests for human T-cell lymphotropic virus type I among blood donors following influenza vaccination, 1992. AB - From October 31 through December 15, 1991, 10 blood donors to the American Red Cross Blood Services, Badger Region (ARCBS), were found to have false-positive screening enzyme-linked immunosorbent assays (ELISAs) for antibodies to two or more of the following viruses: human immunodeficiency virus type 1 (HIV-1), human T-cell lymphotrophic virus type 1 (HTLV-I), and hepatitis C virus (HCV). An investigation by the Division of Health, Wisconsin Department of Health and Social Services (WDOH), and the ARCBS indicated that the risk for false-positive reactivity was associated with antecedent receipt of influenza vaccine formulated for the 1991-92 season. In March 1992, the ARCBS began use of newly available ELISAs for anti-HIV (HIVAB, HIV-1/HIV-2 (rDNA) EIA [Abbott Laboratories, Abbott Park, Illinois]) and anti-HCV (HCV 2.0 ELISA [Ortho Diagnostic Systems, Raritan, New Jersey]), while continuing to test with the ELISA for anti-HTLV-I [HTLV-I ELISA (Abbott Laboratories) used in 1991. From January 1 through October 13, 1992, the ARCBS identified 19 blood donors with repeatedly reactive ELISAs for HTLV-I. However, from October 14 through November 10, 15 false-positive ELISAs for HTLV-I were reported by the ARCBS to the WDOH. As a result of this increase, the ARCBS conducted a case-control study to assess the relation between influenza vaccination and testing positive for HTLV-I. This report summarizes the results of the study. PMID- 8446102 TI - Reconstitution of ligand-mediated glucocorticoid receptor activity by trans acting functional domains. AB - Glucocorticoid receptors (GRs) are ligand-inducible transcription factors that contain several functional domains. We tested whether GR activity can be reconstituted using domains expressed in separate molecules. Hence, we developed a general approach in which proteins can be individually expressed but interact specifically through the leucine zippers of c-Jun and c-Fos fused to each protein. The GR was divided into two different fragments, one encoding the N terminal trans-activation and DNA-binding domains and conferring constitutive activity to a glucocorticoid-responsive reporter gene, and one containing the C terminal, ligand-binding domain. Coexpression of the trans-activation-DNA-binding domain and the ligand-binding domain fragments leads to reconstituted ligand regulated GR activity that is completely dependent on the presence of compatible zippers. These results suggest that, in GRs and perhaps other members of the steroid/thyroid hormone receptor superfamily, ligand-mediated function does not require that these domains be present in cis, but that they can also function in trans. This, together with the absence of interdomain dimerization signals, also suggests that these domains possibly evolved from separate genes. PMID- 8446103 TI - Extinction of insulin-like growth factor II gene expression in intratypic hybrids of rat liver cells. AB - The expression of the developmentally regulated insulin-like growth factor II (IGF-II) gene has been studied in somatic cell hybrids derived from rat liver cells. BRL3A cells, dedifferentiated variants of rat hepatocytes, producing high levels of IGF-II, were fused to BRL30E or FAO cells of the same embryonic lineage but not expressing detectable levels of IGF-II mRNA. We report here that the IGF II gene is subject to extinction, since its specific RNA levels are decreased both in heterokaryons and stable cell hybrids. Transcriptional analysis in isolated nuclei from parental and hybrid cells showed that the IGF-II gene is transcribed at a similar rate in all cell types. Likewise, the stability of IGF II cytoplasmic mRNA was equivalent in the high-expressing parental cells and in the hybrids. In contrast, the distribution of IGF-II mRNA between the nuclear and the cytoplasmic compartments differed markedly in parental and hybrid cell lines. The data presented show that the expression of the IGF-II gene is subject to a dominant negative control and suggest that the phenomenon involves mechanisms that operate at the posttranscriptional level. PMID- 8446104 TI - Prostaglandin E2 inhibits alpha 1(I)procollagen gene transcription and promoter activity in the immortalized rat osteoblastic clonal cell line Py1a. AB - High concentrations of prostaglandin E2 (PGE2) inhibit collagen synthesis and reduce alpha 1(I)procollagen messenger RNA (mRNA) levels in cultured fetal rat calvariae. To examine the mechanism of this effect, we used the immortalized rat osteoblastic clonal cell line, Py1a. PGE2 at 1 microM inhibited the incorporation of [3H]proline into collagenase-digestible protein (CDP) and increased incorporation into noncollagen protein, whereas 0.1 microM PGE2 increased both CDP and noncollagen protein labeling. Because insulin-like growth factor-I (IGF I) is an anabolic hormone in bone and PGE2 can increase its production, we added exogenous IGF-I (10 nM) to Py1a cultures. In the presence of IGF-I, PGE2 from 10 nM to 1 microM had only an inhibitory effect on CDP labeling and alpha 1(I)procollagen mRNA levels. PGE2 at 1 microM decreased the rate of alpha 1(I)procollagen gene transcription in the presence or absence of IGF-I, determined by a nuclear run-on assay. Py1a cells were stably transfected with chimeric genes containing varying lengths of the 5'-upstream region of the rat alpha 1(I)procollagen promoter fused to the chloramphenicol acetyl transferase (CAT) reporter gene. In cells transfected with ColCAT 3.6, which contains 3520 base pairs of 5'-upstream DNA, CAT activity was inhibited by PGE2, but the inhibition was less than that observed for CDP labeling. With smaller 5'-upstream regions, there was no inhibitory effect of PGE2. These results demonstrate that PGE2 inhibits alpha 1(I)procollagen gene transcription and the activity of a region between -3.5 and -2.3 kilobases of the 5'-upstream collagen gene promoter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446105 TI - Characterization of two cis-acting DNA elements involved in the androgen regulation of the probasin gene. AB - The location and sequence of androgen responsive elements (AREs) in the 5' flanking DNA of the androgen-regulated rat probasin (PB) gene were determined. The DNA- and steroid-binding domains of the rat androgen receptor [glutathione-S transferase (GST)-AR1] and the DNA-binding domain and hinge region alone (GST AR2) were expressed in Escherichia coli as isopropyl-B-D-thioglactopyranoside induced fusion proteins with GST and purified using glutathione affinity chromatography. Band shift assays indicated that the AR1 peptide was at least five times more effective than AR2 in binding to PB 5'-flanking DNA (-426 to +28), although both gave qualitatively similar patterns and were displaced by anti-AR antibodies. DNase I footprinting experiments revealed two putative AREs: one between positions -236 and -223 (ARE-1) and the other between -140 and -117 (ARE-2). Hormonal regulation of PB was determined by cotransfecting reporter constructions containing the PB 5'-flanking region (-426 to +28) linked to the bacterial chloramphenicol acetyl transferase (CAT) gene with androgen, glucocorticoid, or progesterone receptor expression vectors into human prostatic carcinoma cells (PC-3). PB-CAT gene expression was more effectively induced by androgens than by glucocorticoids or progestins. Both 5'- and 3'-deletion mapping of the PB 5'-flanking DNA revealed that ARE-1 and ARE-2 were required for androgen regulation. A single base mutation in either ARE resulted in a more than 95% loss of androgen induction of CAT. In comparable transfection experiments, the PB hormone-responsive elements showed a greater induction by androgens than did mouse mammary tumor virus or tyrosine aminotransferase elements. Thus, the preferential androgen regulation of the PB gene involves the participation of two different cis-acting DNA elements that bind AR. PMID- 8446106 TI - Substitution of valine-865 by methionine or leucine in the human androgen receptor causes complete or partial androgen insensitivity, respectively with distinct androgen receptor phenotypes. AB - We have identified two different single nucleotide missense substitutions at valine-865 in exon 7 of the human androgen receptor (AR) gene in two families with androgen resistance. Val-->methionine is associated with the complete syndrome; Val-->leucine is associated with the partial form. In genital skin fibroblasts, both alterations yield a normal maximum binding capacity, but an increased apparent equilibrium dissociation constant for all androgens tested. In genital skin fibroblasts, Val865-Met A-R complexes have increased rate constants of dissociation with 5 alpha-dihydrotestosterone, and the nonmetabolized ligands methyltrienolone or mibolerone (MB); their Val865-Leu counterparts have increased rates with methyltrienolone and MB, but not with 5 alpha-dihydrotestosterone. In transiently transfected COS-1 or PC-3 cells, Met865 AR is more severely impaired than Leu865 AR in transactivating two different androgen-responsive reporter constructs, thereby correlating with clinical phenotype. In COS-1 cells exposed to MB for 74 h, this relative impairment correlates with the relative instability of the MB-binding activity of each mutant AR, suggesting that their respective intrinsic transcriptional regulatory competence is normal. Notably, these mutant ARs lose significantly more MB-binding activity than immunoreactivity, suggesting that prolonged MB exposure induces them to adopt a nonbinding state. The position homologous to Val865 in the AR is occupied by Leu or Met in the three steroid receptors closely related to the AR. This indicates the structural subtlety that underlies the steroid-binding activity of different steroid receptors. PMID- 8446107 TI - Steroid receptors and their associated proteins. PMID- 8446108 TI - Molecular cloning and expression of an abundant rabbit ovarian protein with 20 alpha-hydroxysteroid dehydrogenase activity. AB - An abundant 37-kDa protein, which comprises up to 30% of the soluble proteins of the ovary, has been found to have 20 alpha-hydroxysteroid dehydrogenase (20 alpha HSD) activity. The steroidogenic enzyme 20 alpha HSD regulates the conversion of progesterone to 20 alpha-hydroxyprogesterone in many mammalian species. Complimentary DNA clones encoding a unique and abundant 20 alpha HSD were isolated from a mature rabbit ovary library using guinea pig antisera generated to the purified 37-kDa protein and from a 5' EcoRI fragment from the initial positive clone. A full-length cDNA clone of 1217 basepairs encoding a 323-amino acid protein with an estimated mol wt of 37 kilodaltons was obtained. Amino acid sequence data indicate a similarity to human chlordecone reductase, bovine lung prostaglandin F synthase, human aldose reductase, human aldehyde reductase, and frog lens rho-crystallin, placing rabbit ovarian 20 alpha HSD in the aldo-keto reductase family of proteins. Northern blot analysis demonstrated a 1.2-kilobase mRNA in the interstitial tissue of mature rabbit ovaries and, to a lesser extent, in corpora luteal tissue. 20 alpha HSD was expressed in bacteria as a recombinant protein and was shown to possess enzymatic activity, preferring NADP as a cofactor. These studies demonstrate that an abundant ovarian protein belonging to the superfamily of NADP-dependent aldo-keto reductases has 20 alpha HSD activity. This is the first example of an abundant crystallin-related protein with known enzymatic activity in a tissue other than the lens. PMID- 8446109 TI - Transforming growth factor-beta (beta 1, beta 2, and beta 3) gene expression and action during pubertal development of the seminiferous tubule: potential role at the onset of spermatogenesis. AB - The potential role of transforming growth factor-beta (TGF beta) as a mediator of cell-cell interactions during the pubertal development of the seminiferous tubule was examined. Mesenchymal-derived peritubular cells and epithelial-like Sertoli cells were isolated from prepubertal, midpubertal, and late pubertal rat testes. The developmental expression of the multiple forms of TGF beta (TGF beta 1, -beta 2, and -beta 3) in whole testis and isolated somatic cell types was determined using a nuclease protection analysis. TGF beta 1 and TGF beta 2 mRNA expression was predominant in the immature testis and decreased at the onset of puberty. TGF beta 3 mRNA expression, the most abundant form of TGF beta present, peaked at an early pubertal stage, coincident with the initiation of spermatogenesis. Peritubular and Sertoli cells expressed each isoform of TGF beta during development. Peritubular cell mRNA expression of TGF beta 1, -beta 2, and -beta 3 decreased during pubertal development upon differentiation of this cell type. Sertoli cell expression of TGF beta 1 increased slightly and plateaued during pubertal development. TGF beta 2 mRNA expression was evident only in immature prepubertal Sertoli cells. Sertoli cell mRNA expression of TGF beta 3 increased transiently at the onset of puberty, corresponding with the peak of expression observed during the analysis of whole testicular development. Immunoblot analysis indicated that both cultured peritubular and Sertoli cells can produce the proteins for TGF beta 1, -beta 2, and -beta 3. Analysis of the hormonal regulation of TGF beta expression revealed that FSH caused a dramatic decrease in Sertoli cell TGF beta 2 expression while having no effect on TGF beta 1 or TGF beta 3 expression. Potential actions of TGF beta in the seminiferous tubule were also examined. TGF beta 1 inhibited TGF alpha-induced [3H]thymidine incorporation into peritubular cell DNA with cells from each developmental stage examined. TGF beta 1 had no effect on Sertoli cell proliferation. Previously, germinal cells have been shown to be responsive to TGF beta. This study demonstrates the potential of having a unique hormone-dependent pattern of TGF beta isoform expression during postnatal organ development. Observations demonstrate that the suppression of TGF beta 2 expression, in part in response to FSH, and the transient increase in TGF beta 3 expression correlate with the onset of puberty and the induction of spermatogenesis. PMID- 8446110 TI - [Immunologic importance of breast milk]. AB - Breast milk contains a great variety of immunological factors. Besides unspecific humoral factors (Lactoferrin, Lysozyme etc.) various immunoglobulins (IgA, IgG, IgM) can be identified. Secretory IgA which is resistant against proteolytic digestion constitutes the greatest fraction of immunoglobulins. Specific activity of S-IgA is directed against a great number of entero- and bronchopulmonary pathogenic organisms. In lactating mothers the common mucosal defense system has been shown to contribute to the de-novo-synthesis of S-IgA via the entero bronchomammalian axis. In addition, the formation of antiidiotypic antibodies in the infant is induced by maternal milk antibodies. Among the cellular components, breast milk macrophages seem to play a role in the local protection of the infants' intestinum; the physiologic function of T-lymphocytes has not been elucidated yet. Despite contradictory results, a number of epidemiological studies provide evidence that breast feeding is associated with a reduced incidence of gastrointestinal and pulmonary infectious diseases in infants. PMID- 8446111 TI - [Pediatrics: the development of a clinical discipline]. AB - "80 years Department of Pediatrics at the University of Giessen (1912-1992)": Occasion to remember the development of this discipline obtaining only late independent Professorships and Clinics at German Universities. The reasons therefore are discussed. PMID- 8446112 TI - [Thrombosis: an underestimated complication of central catheters? Subclavian vein, vena cava and renal vein thrombosis after silastic catheters]. AB - Besides systemic infections venous thromboses constitute major complications of central lines used in neonatal intensive care. Male triplet born at 25 weeks of gestation, birthweight 460 g during his first developed a catheter-associated thrombosis of the left vena subclavia without clinical symptoms. In addition, a second catheter-induced thrombosis of the vena cava inferior and right vena renalis manifested with typical clinical symptoms at an age of 4 weeks. Coagulation tests were normal. 7 months later the size and the renal function of the right kidney were markedly reduced. The incidence of catheter-associated thrombotic complications has not been defined yet; thromboses may develop without clinical signs. There is evidence that the rate of this complication is higher than generally assumed. PMID- 8446113 TI - [Extensive subdural hematoma with brain edema and brain death. Sequela of late manifestation of vitamin K deficiency]. AB - After an uneventful pregnancy and birth without vitamin-K-prophylaxis a seven week-old breast-fed infant showed a subdural hemorrhage caused by vitamin-K deficiency. Laboratory investigations indicated a subclinical cholestasis. The infant died 3 days later. This case once again provides a strong argument for routine vitamin-K-prophylaxis after birth for all infants. PMID- 8446114 TI - [Successful operation of right ventricular cardiac fibroma in an infant]. AB - Cardiac tumors are rare in infants. We describe the diagnostic procedure and the good postoperative outcome despite the very large cardiac fibroma. PMID- 8446115 TI - [Botulism in infancy. A rare cause of floppy infant syndrome]. AB - In Europe only a few cases of infantile botulism have been identified. A two month old infant fell ill with feeding difficulties and profound general weakness. Clostridium botulinum and botulinal toxin, the causative agents, were isolated from the patients stool. We describe the typical clinical symptoms and the investigations confirming the diagnosis. PMID- 8446116 TI - [Obese children and adolescents. Waist-hip ratio and cardiovascular risk]. AB - In obese adults body fat distribution is more closely associated with cardiovascular risk factors and cardiovascular disease, type II diabetes and gout than the degree of obesity; the android, abdominal body fat pattern carrying more risk than the gynoid, femoral form. For characterizing the different types of fat distribution the ratio of waist to hip girth (WHR) is commonly used. The question was whether these facts can already be demonstrated in obese children. In the studied group of 69 obese children, aged between 3-16 years (mean = 10.8 years) with a mean of 47% overweight no correlations between percentage overweight and waist hip ratio could be found. Better correlations of serum triglycerides, total and LDL-cholesterol, the atherogenic index LDL/HDL-cholesterol, fasting insulin level, oral glucose tolerance and blood pressure were obtained with percentage overweight than with waist-hip-ratio. HDL-cholesterol was the only parameter showing better and significant correlation with waist-hip-ratio than with percentage overweight. These results are in contrast to the situation in adults but are comparable with other studies in normal weighed and obese children, where correlations of waist hip ratio with body fat and risk factors were low in childhood, becoming higher in adolescence. Only after onset of puberty does waist hip ratio seem to be an indicator for body fat distribution and for possibly associated additional risk factors as in adults. For estimation of the cardiovascular risk in obese children, determination of WHR need not to be recommended.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446117 TI - [Glucose homeostasis in cystic fibrosis. Oral glucose tolerance test in comparison with formula administration]. AB - BACKGROUND: Glucose tolerance is often impaired in Cystic Fibrosis. The impact of this condition on enteral nutritional support in case of malnourishment remains to be studied. METHOD: In this study the glucose-, C-peptide- and insulin responses to an OGTT and a standard enteral formula load were investigated in 19 non-diabetic CF-patients. Each test was performed with a carbohydrate load of 1.75 g/kg bodyweight. RESULTS: 11 patients had a normal OGTT (Group I) and 8 had an impaired glucose tolerance (Group II). After the formula load the glucose concentrations were significantly lower than after the OGTT at 30, 60, and 90 min in both groups and at 120 min in group II only. In group II the glucose values exceeded 6.7 mmol/l at 120 min after both OGTT and formula load and were significantly higher than in group I. The food glycaemic index, a parameter for comparison of glucose response to different diets was calculated. It ranged from 30 to 80% in both groups. An increased C-peptide- and insulin-secretion was found in patients with impaired glucose tolerance. CONCLUSIONS: The condition of impaired glucose tolerance must be considered for enteral hyperalimentation of Cystic Fibrosis-patients. The selection of formulas for nutritional support should be based on the calculation of the Food Glycemic Index because of its high interindividual variability. PMID- 8446118 TI - [Spontaneous regression of neonatal ovarian cysts. A prospective study]. AB - With routine use of ultrasonography in pregnancy and newborns neonatal ovarian cysts are discovered more often. In view of the risk of possible complications they still pose a therapeutic problem. Frequent observations of their spontaneous regression suggest a conservative treatment. From 1988 to 1991 we investigated 21 newborns with the sonographic diagnosis of an ovarian cyst. In three children the cysts were resected primarily because of clinical symptoms or uncertain diagnosis. 18 children were controlled regularly by ultrasound. One of these had a mesenteric cyst, which had to be removed at the age of four months. In the others a complete resolution of all 19 ovarian cysts could be documented after intervals of up to 16 months. In these patients a clinically relevant complication did not occur. Therefore a conservative strategy with regular ultrasound controls is justified in all children with uncomplicated neonatal ovarian cysts. A surgical intervention is indicated only in case of complications or uncertain diagnosis. PMID- 8446119 TI - [Proteinuria and enzymuria as leading symptoms of renal and extrarenal diseases in childhood]. PMID- 8446120 TI - [The 150th birthday of Otto Heubner 21 January 1993]. AB - Otto Heubner can be counted among the fathers of pediatry. Beginning as an autodidact, he became pediatrist by chance, holding the first university chair in Germany (1884) exclusively devoted to pediatry; he needed no Dr. med. habil. thesis. Observing the little patients was his primary interest; for the infants treated in the hospital he introduced "aseptic environments". Heubners main scientific achievements were the treatment of infectious and stomach-intestinal diseases. He described "Endarteritis syphilitica" and found Meningococci in the cerebrospinal fluid. "Serious deficiency of digestion" (Coeliac disease) became known through his work. Together with his friend M. Rubner he created the notion of EQ (Nutrition Quotient). Also, he realized the functional effects of orthotic albuminuria. Heubners centers of activity were Leipzig and Berlin, where he had a large community of followers; his successor, recommended by him, was A. Czerny. PMID- 8446121 TI - [Vitamin K prevention in newborn infants. Nutrition Commission of the German Society of Pediatrics]. PMID- 8446122 TI - Far-field potentials. AB - Far-field potentials are produced by neural generators located at a distance from the recording electrodes. These potentials were initially characterized incorrectly as being of positive polarity, widespread distribution, and constant latency; however, recent advances have clearly demonstrated that far-field potentials may be either positive or negative depending upon the location of the electrodes with respect to the orientation of the dipole generator. Additionally, peak latencies in the far-field can vary with alterations in body position and the spatial distribution of far-field potentials, while widespread, is not uniform. Recent studies of far-field potentials suggest how such waveforms are produced when the symmetry of an action potential, as recorded by distant electrodes, is broken by such factors as differing conductivities of volume conductor compartments, direction of action potential propagation, size differentials in adjoining body segments, or the termination of action potential propagation in excitable tissue. Human, animal, and computer experiments support the preceding generalizations. These new explanations are directly applicable to such far-field potentials as the short latency somatosensory-evoked potential. Furthermore, since far-field potentials can also occur in muscle tissue, one should expect that these generalizations will hold with respect to electromyographic potentials. PMID- 8446123 TI - Frequency of acoustic myography during isometric contraction of fresh and fatigued muscle and during dynamic contractions. AB - The frequency of the acoustic myographic (AMG) signal was examined during fresh and fatigued isometric contractions of quadriceps and during dynamic contractions of biceps brachii (BB) in healthy subjects. Recordings were obtained from quadriceps over a range of forces between 10% and 100% maximal voluntary contraction prior to, and 15 minutes after, a fatiguing exercise. Recordings from BB were obtained over a range of submaximal forces (0-8.5 kg) during concentric and eccentric contractions. The mean power frequency (MPF) of the AMG signal was analyzed during each of these contractions by fast-Fourier transform (FFT). The MPF was not significantly different (P > 0.05) during fresh and fatigued contractions of quadriceps and increased quadratically with force in both states (r = 0.81, fresh; r = 0.77, fatigued). During concentric contractions of BB the MPF initially increased with force, but then decreased at the heavier loads (> 5.5 kg). The MPF of eccentric contractions did not significantly (P > 0.05) alter with force. The AMG MPF was within a similar low frequency range for both muscles, during different types of contraction, and was unaltered with fatigue. PMID- 8446124 TI - Determining heart-rate variability: comparing methodologies using computer simulations. AB - Heart rate variation due to respiration is a window onto autonomic nervous system function and many measures exist that quantify this variability. Computer-based simulations of 1-minute deep-breathing tests, along with common artifacts, were used to compare the most frequently used measures. We found distinct differences in the performance of the measures. Some measures (e.g., SDRR and MSSD) are strongly influenced by the underlying mean heart rate while others (e.g., Max-Min and SDHR) are not. All of the measures tested, except R, were influenced by both shifting mean heart rate and single-beat anomalies. R, on the other hand, is strongly influenced by test duration and breathing asynchronies. Sensitivity to phenomena unrelated to ANS function can reduce the diagnostic discrimination of these measures. We suggest simple improvements to the measures and discuss how some measures may be theoretically superior to others. PMID- 8446125 TI - Relationship between stimulus strength and the cutaneous silent period. AB - During sustained muscle contraction, an interval of reduced activity follows an electrical cutaneous stimulus, called the cutaneous silent period (CSP). To evoke a CSP, a single stimulus must be painful. We used single sural nerve stimuli to evoke a CSP in ipsilateral soleus muscle, and studied the relationships between stimulus strength, sensory action potential (SAP) morphology, and subjective experience. Near nerve electrodes were employed to record the sural SAP in order to record activity in slower conducting fibers in addition to A alpha fibers. In 6 normal subjects, the stimulus strength required to evoke a CSP ranged from 8 to 10 times threshold intensity. Pain threshold was slightly below that necessary to evoke the CSP. SAP shape changed with stimulus strength; main component amplitude occasionally increased as strength increased beyond 10 times threshold, and slowly conducting late components became more prominent. At stimulus intensities or at less than CSP threshold, components were seen conducting from 15-20 m/s that were not observed at lower intensities. We suggest that activation of sensory axons with conduction velocities in the range of A delta fibers are necessary to evoke the CSP, and that their potentials can be discerned in the SAP. PMID- 8446126 TI - Reduced capability of transmitting high frequency impulses in tail nerves of diabetic rats. AB - The effect of long-term (40 min) high frequency stimulation (143 Hz) of sensory motor tail nerves was studied in normal and in streptozotocin-diabetic rats. The study comprised a 6-week period, repeating the test at 2-week intervals. In the initial (prediabetic) study, single experiments showed a mild depression of the peak-to-peak amplitude during high frequency stimulation, which reversed completely during a subsequent rest period. In normal rats, the amplitude depression was unchanged in repeated tests over a 6-week period. Diabetic rats showed a greater amplitude depression during high frequency stimulation. The difference was statistically significant after 2 weeks, but showed no further change at subsequent tests. The greater decrease in the amplitude in diabetic rats may reflect a depression of the axon membrane function, which may be the functional correlate to the inhibition of the Na/K ATPase activity in diabetes, described by others. Monitoring of the axon membrane functional capacity may have clinical implications in the control of peripheral neuropathies. PMID- 8446127 TI - Sensory potentials evoked by magnetic stimulation of the cervical spine. AB - Magnetic stimulation of cervical spinal roots was shown to elicit sensory potentials (MESP) which could easily be recorded at the fingers with ring electrodes. The latency of the MESP recorded at digit I was significantly shorter and the amplitude higher than of digits III and V. The latencies were largely independent of stimulus strength. In an attempt to localize the place of depolarization, the latencies of these potentials were compared with the N11 of the SEP (reflecting the arrival in the spinal cord) and with F-wave latencies and motor evoked potentials (MEP) to abductor pollicis brevis. The MESP latencies showed a very constant difference with the N11, being 0.6 ms faster. The mean difference between F latency and MEP was 1.2 ms. It is concluded that the origin of these MESPs is very near the spinal foramina, possibly in the sensory ganglia. PMID- 8446128 TI - Muscle ultrasonography and computed tomography in elderly trained and untrained women. AB - Ultrasonography (US) and computed tomography (CT) were compared in studying the associations between long-term physical training and quadriceps muscle mass and structure in female athletes and controls, aged 66-85 years. Muscle cross sectional area (CSA) measured using US correlated highly with that measured using CT, but the latter technique yielded 30% higher values on average. The echo intensity of the fasciae and bone measured by US correlated positively with the mean radiological density and negatively with the relative proportion of fat obtained from CT. Low intramuscular echo intensity was accompanied by high muscle density and low relative proportion of fat. The athletes had larger quadriceps CSA and more discerned fasciae and connective tissue septa but less fat than the controls. The results indicate that US and CT both are useful methods in comparing muscle mass and structure in elderly trained and untrained women. PMID- 8446129 TI - Thermal sensitivity in demyelinating neuropathy. AB - An 8-year-old girl with demyelinating peripheral neuropathy was observed to get markedly weak coincident with a febrile illness. With return of body temperature to normal over 24 hours, her strength improved back to baseline. Subsequently, we studied the effect of temperature on CMAP amplitude of two motor nerves in the patient and two control subjects. Both temperature, measured orally, was raised by immersing the subjects in hot water and lowered by passive cooling. With increase in temperature to 39.5 degrees C, the CMAP amplitudes were reduced by 80% in the patient's nerves compared to only 48% in the control nerves. These changes recovered with cooling to 36.9 degrees C. We conclude that demyelinated peripheral nerves are more susceptible to temperature-induced impulse blocking than healthy nerves and provide the first published evidence of the clinical consequences of this phenomenon in a demyelinating disease other than multiple sclerosis. PMID- 8446130 TI - Sural nerve water in vivo in normal humans measured by magnetic resonance spectroscopy: relation to age, height, gender, and neurological profile. AB - To enable the quantitative assessment of peripheral nerve structure and function, we determined the normal values for sural nerve hydration structure as measured by magnetic resonance proton imaging, and for neurological function with scores for neuropathic symptoms, signs, and nerve conduction properties. Normal human sural nerves contain 24.8 +/- 3.4% water. The structural water content of the nerves did not vary systematically in relation to age, height, gender, sural nerve conduction, neurologic symptoms, or examination deficits. In contrast, the neurological function scores were significantly influenced by age and selectively by height. Both nerve structure and function were stable over a 1-year interval. Measurement of human sural nerve water content in vivo by magnetic resonance proton imaging, and quantitation of the neurological profile of symptoms, signs, and conduction velocity are useful, noninvasive tools for the investigation of diseases in which changes in nerve structure may be related to alterations in nerve function. PMID- 8446131 TI - Long-lasting supernormal conduction velocity after sustained maximal isometric contraction in human muscle. AB - Local muscle fatigue (1 min maximal voluntary contraction) and recovery were studied by means of surface and invasive EMG on elbow flexors to record the changes in muscle fiber conduction velocity (MFCV), median power frequency (MPF), integrated EMG (IEMG), and force. The main finding was a long-lasting "supernormal" MFCV during recovery, for at least 1 hour. After a normalization phase, the MFCV and MPF continued to increase reaching a steady state at supernormal values after 10-12 min. Mean MFCV increase at 20% MVC after 15-min recovery was 0.58 m.s-1 (12%). Postfatigue IEMG values were increased at all contraction levels. In combination with near normal force levels, this resulted in a decrease in "neuromuscular efficiency" (force/IEMG). We suggest that this IEMG increase is mainly a result of the MFCV increase. The MFCV changes in fastest and slowest fibers found with the invasive method indicate a relatively equal effect on type I and II fiber types. A possible explanation of the supernormal MFCV is muscle fiber swelling, in combination with altered membrane properties. PMID- 8446132 TI - Calf muscle hypertrophy, complex repetitive discharges and spinal stenosis. PMID- 8446133 TI - Needle EMG of the diaphragm. PMID- 8446134 TI - Computerized tomography of oropharynx is useful in the diagnosis of oculopharyngeal muscular dystrophy. PMID- 8446135 TI - Electromyography in benign congenital myopathies. PMID- 8446136 TI - Randomized comparison of surveillance intervals after colonoscopic removal of newly diagnosed adenomatous polyps. The National Polyp Study Workgroup. AB - BACKGROUND: The identification and removal of adenomatous polyps and post polypectomy surveillance are considered to be important for the control of colorectal cancer. In current practice, the intervals between colonoscopies after polypectomy are variable, often a year long, and not based on data from randomized clinical trials. We sought to determine whether follow-up colonoscopy at three years would detect important colonic lesions as well as follow-up colonoscopy at both one and three years. METHODS: Patients were eligible if they had one or more adenomas, no previous polypectomy, and a complete colonoscopy and all their polyps had been removed. They were randomly assigned to have follow-up colonoscopy at one and three years or at three years only. The two study end points were the detection of any adenoma, and the detection of adenomas with advanced pathological features (defined as those > 1 cm in diameter and those with high-grade dysplasia or invasive cancer). RESULTS: Of 2632 eligible patients, 1418 were randomly assigned to the two follow-up groups, 699 to the two examination group and 719 to the one-examination group. The percentage of patients with adenomas in the group examined at one and three years was 41.7 percent, as compared with 32.0 percent in the group examined at three years (P = 0.006). The percentage of patients with adenomas with advanced pathological features was the same in both groups (3.3 percent). CONCLUSIONS: Colonoscopy performed three years after colonoscopic removal of adenomatous polyps detects important colonic lesions as effectively as follow-up colonoscopy after both one and three years. An interval of at least three years is recommended before follow up colonoscopy after both one and three years. An interval of at least three years is recommended before follow-up examination after colonoscopic removal of newly diagnosed adenomatous polyps. Adoption of this recommendation nationally should reduce the cost of post-polypectomy surveillance and screening. PMID- 8446137 TI - Quality of life and antihypertensive therapy in men. A comparison of captopril with enalapril. The Quality-of-Life Hypertension Study Group. AB - BACKGROUND: We conducted a multicenter trial comparing two angiotensin-converting enzyme inhibitors to determine whether effects on quality of life during antihypertensive therapy are uniform within this pharmacologic class of agents, and to relate the effects of the drugs on quality of life to objective adverse events, such as the loss of a job or the death of a spouse. METHODS: After a four week washout period when they received placebo, 379 men with mild-to-moderately severe hypertension were randomly assigned to receive captopril (25 to 50 mg twice daily, with or without hydrochlorothiazide) or enalapril (5 to 20 mg per day, with or without hydrochlorothiazide) for 24 weeks. Blood pressure, quality of life, and life events were monitored. Differences between treatments were evaluated by calibrating measures of quality of life with objective life events. RESULTS: Throughout the treatment period, no differences were found in blood pressure, frequency of withdrawal of patients from the study, or major side effects. Patients treated with captopril had more favorable changes in overall quality of life, general perceived health, vitality, health status, sleep, and emotional control (P < 0.05 for each). The changes varied according to the quality of life at base line (P < 0.001); patients with a low quality of life at base line remained stable or improved with either drug, whereas those with a higher quality of life remained stable with captopril but worsened with enalapril. The quality-of-life scales correlated with life events and symptom distress (P < 0.001), and calibration analysis indicated that differences between treatments were clinically important. CONCLUSIONS: Two angiotensin-converting enzyme inhibitors, captopril and enalapril, indistinguishable according to clinical assessments of efficacy and safety, had different effects on quality of life. Calibration with life events showed that drug-induced changes are substantial and that the different effects of these two agents on quality of life can be clinically meaningful. PMID- 8446138 TI - Single-drug therapy for hypertension in men. A comparison of six antihypertensive agents with placebo. The Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents. AB - BACKGROUND: Characteristics such as age and race are often cited as determinants of the response of blood pressure to specific antihypertensive agents, but this clinically important issue has not been examined in sufficiently large trials, involving all standard treatments, to determine the effect of such factors. METHODS: In a randomized, double-blind study at 15 clinics, we assigned 1292 men with diastolic blood pressures of 95 to 109 mm Hg, after a placebo washout period, to receive placebo or one of six drugs: hydrochlorothiazide (12.5 to 50 mg per day), atenolol (25 to 100 mg per day), captopril (25 to 100 mg per day), clonidine (0.2 to 0.6 mg per day), a sustained-release preparation of diltiazem (120 to 360 mg per day), or prazosin (4 to 20 mg per day). The drug doses were titrated to a goal of less than 90 mm Hg for maximal diastolic pressure, and the patients continued to receive therapy for at least one year. RESULTS: The mean (+/- SD) age of the randomized patients was 59 +/- 10 years, and 48 percent were black. The average blood pressure at base line was 152 +/- 14/99 +/- 3 mm Hg. Diltiazem therapy had the highest rate of success: 59 percent of the treated patients had reached the blood-pressure goal at the end of the titration phase and had a diastolic blood pressure of less than 95 mm Hg at one year. Atenolol was successful by this definition in 51 percent of the patients, clonidine in 50 percent, hydrochlorothiazide in 46 percent, captopril in 42 percent, and prazosin in 42 percent; all these agents were superior to placebo (success rate, 25 percent). Diltiazem ranked first for younger blacks (< 60 years) and older blacks (> or = 60 years), among whom the success rate was 64 percent, captopril for younger whites (success rate, 55 percent), and atenolol for older whites (68 percent). Drug intolerance was more frequent with clonidine (14 percent) and prazosin (12 percent) than with the other drugs. CONCLUSIONS: Among men, race and age have an important effect on the response to single-drug therapy for hypertension. In addition to cost and quality of life, these factors should be considered in the initial choice of a drug. PMID- 8446139 TI - Use of multiple drugs among adolescents who use anabolic steroids. AB - BACKGROUND: Because adolescent users of anabolic steroids are concerned with increasing muscle size and strength, they may be unique among substance users and unlikely to use other drugs. Alternatively, if the factors that cause the use of anabolic steroids are similar to those associated with the use of other substances, adolescents who use anabolic steroids would be expected to report use of other drugs as well. METHODS: We administered a questionnaire based on the 1989 Secondary School Health Risk Survey and the 1990 Youth Risk Behavior Survey of the Centers for Disease Control and Prevention to 1881 students enrolled in compulsory health-science classes (mean [+/- SD] age, 14.9 +/- 1.0 years) in the Richmond County, Georgia, school system. RESULTS: A higher percentage of boys (6.5 percent) than girls (1.9 percent, P < or = 0.001) reported using anabolic steroids without a doctor's prescription. Among ninth-grade students only, 5.4 percent of boys and 1.5 percent of girls reported using anabolic steroids (P < or = 0.001). Among users of anabolic steroids, 25 percent reported sharing needles to inject drugs. The frequency of anabolic-steroid use was significantly (P < 0.001) associated with the frequency of use in the previous 30 days of cocaine (r = 0.44), injectable drugs, alcohol (r = 0.23), marijuana (r = 0.42), cigarettes (r = 0.25), and smokeless tobacco (r = 0.40). On the basis of multiple regression analysis, the use of marijuana, shared needles, smokeless tobacco, and cocaine accounted for 33 percent of the variation in anabolic-steroid use among the ninth grade students. CONCLUSIONS: In our study, adolescent users of anabolic steroids were likely to use other drugs as well, and many were sharing needles. PMID- 8446140 TI - Assessing the implementation of physician-payment reform. AB - BACKGROUND: The Medicare program fundamentally changed its system of payment for physicians' services in 1992. Controversy over the new Medicare fee schedule has focused on three issues: the adequacy of the conversion factor used to translate resource-based relative-value units into fees; the ability of the new payment system to capture differences in work between surgeons and physicians in other specialties; and the allocation of practice expenses across services. METHODS: Using a standard service in each specialty, we developed simulation methods to assess the implementation of physician-payment reform. With these methods we calculated the potential net income for each specialty, as generated by different payment scenarios, including the Medicare fee schedule. RESULTS: We found that Medicare's current monetary-conversion factor yields an unreasonably low level of income for most specialties. Furthermore, the Medicare fee schedule misallocates practice expenses; invasive services are reimbursed for more than actual expenses, and medical services are reimbursed for less. Thus, physicians continue to be paid more generously for invasive services. Finally, the Medicare fee schedule does recognize the wide differences in the intensity of work performed by physicians in various specialties. CONCLUSIONS: The misallocation of practice expenses in the Medicare fee schedule results in serious underpayment for medical services. We think it likely that physicians compensate by performing more lucrative services, such as diagnostic tests. Even if legislation is passed to deal with the misallocation of expenses, the current conversion factor still produces unreasonably low levels of payment overall, which could dissuade those considering a career in medicine from entering the field. Finally, the simulation method we developed can be used as a tool for fee negotiations. PMID- 8446141 TI - Recruitment, retention, and follow-up of graduates of a program to increase the number of family physicians in rural and underserved areas. AB - BACKGROUND: To help address the geographic and specialty maldistribution of physicians, Jefferson Medical College initiated the Physician Shortage Area Program (PSAP) in 1974. This unique program, which combines a selective medical school admissions policy with a special educational program, has been shown to be successful in increasing the number of family physicians in rural and underserved areas, but it is not known whether they remain in this type of practice. METHODS: Graduates of the PSAP were tracked longitudinally and compared with their non PSAP classmates. Information was obtained about the retention of family physicians in rural areas and areas with a physician shortage over the previous five years, the geographic and specialty choices of more recent graduates, and the recruitment of applicants into the program. RESULTS: Of the 47 PSAP graduates from the classes of 1978 through 1981, reported on earlier, the number who combined a career in family medicine with practice in a rural area or one with a physician shortage remained unchanged, although there was substantial attrition among non-PSAP graduates practicing family medicine in rural (32 percent) and underserved (40 percent) areas. Among the 101 PSAP graduates of the classes of 1982 through 1986, the results were similar to those for the first four classes. Overall, PSAP graduates from the classes of 1978 through 1986 were approximately four times as likely as non-PSAP graduates to practice family medicine (55 percent vs. 13 percent), to practice in a rural area (39 percent vs. 11 percent), and to practice in underserved areas (33 percent vs. 8 percent). They were approximately 10 times more likely to combine a career in family medicine with practice in a rural (26 percent vs. 3 percent) or underserved (23 percent vs. 2 percent) area. Overall, 85 percent of PSAP graduates were either practicing a care specialty or practicing in a rural or small metropolitan area or one with a shortage of physicians. In parallel with national trends, the number of applicants and matriculants to the program decreased during the past decade, so that the percentage of available places filled decreased from 97 percent to 33 percent. However, there has been a recent increase in the number of applicants and matriculants. CONCLUSIONS: The results of this study indicate that the PSAP was successful in increasing the number of family physicians in rural and underserved areas as well as in retaining them. This suggests that medical schools can have a substantial influence on the distribution of physicians according to specialty choice and the geographic location of their practices, principally through admission criteria. PMID- 8446142 TI - Managing primary care in the United States and in the United Kingdom. PMID- 8446143 TI - Too old for what? PMID- 8446144 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 13-1993. A 74-year-old woman with rapidly progressing renal failure after an upper respiratory tract infection. PMID- 8446145 TI - Antihypertensive therapy--efficacy and quality of life. PMID- 8446146 TI - Specialty distribution of U.S. physicians--the invisible driver of health care costs. PMID- 8446147 TI - Assisted death and physician-assisted suicide. PMID- 8446148 TI - Assisted death and physician-assisted suicide. PMID- 8446149 TI - Assisted death and physician-assisted suicide. PMID- 8446151 TI - Assisted death and physician-assisted suicide. PMID- 8446150 TI - Assisted death and physician-assisted suicide. PMID- 8446152 TI - ACE inhibitors after myocardial infarction. PMID- 8446153 TI - ACE inhibitors after myocardial infarction. PMID- 8446154 TI - ACE inhibitors after myocardial infarction. PMID- 8446155 TI - ACE inhibitors after myocardial infarction. PMID- 8446156 TI - Contamination of a finger-stick device. PMID- 8446157 TI - Health care reform in Minnesota. PMID- 8446158 TI - Health care reform in Minnesota. PMID- 8446159 TI - Do health maintenance organizations control costs or shift costs? PMID- 8446160 TI - You're never too old. PMID- 8446161 TI - The doctor with two heads. The patient versus the costs. PMID- 8446162 TI - Iceman in the cold light of day. AB - The discovery of a Neolithic corpse in an alpine glacier in 1991 attracted widespread attention. What has happened in the eighteen months since then reflects badly on European science. PMID- 8446163 TI - A disappointing decade of AIDS. PMID- 8446164 TI - Running to catch the ball. PMID- 8446165 TI - Tetramer data reinterpreted. PMID- 8446166 TI - Similarity of active-site structures. PMID- 8446167 TI - Sporozoite invasion. PMID- 8446168 TI - Kessler stays, Healy goes. PMID- 8446169 TI - US judge throws out laboratory rules for dogs, primates. PMID- 8446170 TI - Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. AB - Amyotrophic lateral sclerosis (ALS) is a degenerative disorder of motor neurons in the cortex, brainstem and spinal cord. Its cause is unknown and it is uniformly fatal, typically within five years. About 10% of cases are inherited as an autosomal dominant trait, with high penetrance after the sixth decade. In most instances, sporadic and autosomal dominant familial ALS (FALS) are clinically similar. We have previously shown that in some but not all FALS pedigrees the disease is linked to a genetic defect on chromosome 21q (refs 8, 9). Here we report tight genetic linkage between FALS and a gene that encodes a cytosolic, Cu/Zn-binding superoxide dismutase (SOD1), a homodimeric metalloenzyme that catalyzes the dismutation of the toxic superoxide anion O2.- to O2 and H2O2 (ref. 10). Given this linkage and the potential role of free radical toxicity in other neurodenegerative disorders, we investigated SOD1 as a candidate gene in FALS. We identified 11 different SOD1 missense mutations in 13 different FALS families. PMID- 8446171 TI - MHC class II-positive epithelium and mesenchyme cells are both required for T cell development in the thymus. AB - T lymphocytes are produced in the thymus from precursors originating in the haemopoietic tissues. On entering the thymus, they undergo a programme of proliferation, T-cell receptor (TCR) gene rearrangement, differentiation and repertoire selection. Although the thymus provides a unique environment for these events, the role of the thymic stroma in regulating specific developmental stages is not well understood. We therefore devised an in vitro system to study the role of individual thymic stromal components in T-cell development. We report here that the development of TCR-CD4-CD8-T-cell precursors into TCR+ cells expressing CD4 and/or CD8 requires the presence of both major histocompatibility complex class II+ epithelial cells and fetal mesenchyme. The requirement for mesenchymal support can be mapped to the initial stages of intrathymic development because the later stages of maturation, from double-positive CD4+CD8+ thymocytes into single-positive CD4+ or CD8+ cells, can be supported by epithelial cells alone. We also show that the requirement for mesenchymal cells can be met by cells of the fibroblast line 3T3 (but not by supernatants from these cells). To our knowledge, these findings provide the first direct evidence that mesenchymal as well as epithelial cells are involved in T-cell development, and suggest that their involvement is stage-specific and likely to be dependent on short-range or contact-mediated interactions. PMID- 8446172 TI - Alzheimer amyloid protein precursor complexes with brain GTP-binding protein G(o) AB - The most characteristic change in progressive dementia of Alzheimer's type is a tissue deposit of amyloid beta/A4 protein, which is derived from its precursor protein APP (ref.2). Structural alterations of APP are implicated in the pathogenesis of Alzheimer's disease, but it is not known how they cause the disease. Although APP has a receptor-like architecture, is located on the neuronal surface, and has a conserved cytoplasmic domain, no receptor function has been demonstrated for APP. Here we report that APP forms a complex with G(o), a major GTP-binding protein in brain. The cytoplasmic APP sequence His 657-Lys 676 shows a specific G(o)-activating function and is necessary for complex formation. G(o) protein treated with GTP-gamma S lost the ability to associate with APP. This suggests that APP is a receptor coupled to G(o) and that abnormal APP-G(o) signalling is involved in the Alzheimer's disease process. PMID- 8446173 TI - A new component of the transcription factor DRTF1/E2F. AB - Transcription factor DRTF1/E2F coordinates events in the cell cycle with transcription by its cyclical interactions with important regulators of cellular proliferation like the retinoblastoma tumour-suppressor gene product (Rb) and the Rb-related protein, p107 (refs 1-8). DRTF1/E2F binding sites occur in the control regions of genes involved in proliferation, and both Rb and p107 repress the capacity of DRTF1/E2F to activate transcription (refs 11, 12; M. Zamanian and N.B.L.T., manuscript submitted). Mutant Rb proteins isolated from tumour cells are unable to bind DRTF1/E2F (refs 11-13), and certain viral oncoproteins, such as adenovirus E1A, sequester Rb and p107 in order to free active DRTF1/E2F (refs 5, 11, 12, 14, 15). Here we report the isolation of a complementary DNA encoding DRTF1-polypeptide-1 (DP-1), a major sequence-specific binding protein that is present in DRTF1/E2F, including Rb- and p107-associated DRTF1/E2F. The DNA binding domain of DP-1 contains a region that resembles that of E2F-1 (refs 16, 17), and recognizes the same sequence. DRTF1/E2F thus appears to contain at least two sequence-specific DNA-binding proteins. PMID- 8446174 TI - Peripherin and the vision thing. PMID- 8446175 TI - [Lipopeptides as natural adjuvants for vaccines from Gram-negative bacteria]. AB - Bacterial cell wall components such as lipopolysaccharide, a variety of membrane proteins, murein, and lipoprotein can act as immunoadjuvants for bacterial vaccines, thus enhancing protection from bacterial infections. Synthetically prepared N-terminal parts of the lipoprotein from Enterobacteria carrying three fatty acid residues or lipopeptide analogs containing one to four aminoacids bound to S-glycerylcysteine act as potent immunoadjuvants in vivo in combination with or covalently linked to antigens. Here we demonstrate that the supplementation of Salmonella vaccines with these synthetic lipopeptides significantly enhances their vaccine efficiency in mice. Variations in the native lipopeptide structure regarding chain length and amino acid sequence of the peptide moiety, as well as modifications of the lipoamino acid, lead to reduction or even complete loss of the adjuvant activity. The immunoadjuvant properties of the lipopeptides as described here are mediated by an enhancement of the humoral immune response. PMID- 8446176 TI - Historical aspects of research on the vertebrate olfactory system. AB - The historical review concentrates on M. Schultzes ingenious investigations in the 19th century. His work contains numerous methodological details, vigorous defense against theoretical and experimental criticism, and precise descriptions of the olfactory mucosa throughout the vertebrate kingdom, and left little for further investigations for many years; practically all of his careful observations proved to be correct. PMID- 8446177 TI - Amplification of a genomic sequence in 19th century human bone DNA. PMID- 8446178 TI - Growth inhibition of human colon adenocarcinoma-derived Caco-2 cells by 1,25 dihydroxyvitamin D3 and two synthetic analogs: relation to in vitro hypercalcemic potential. AB - The effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and of two synthetic analogs, 1,25S,26-tri-hydroxy-delta 22-vitamin D3 (1,25,26(OH)3-22ene-D3, Ro 23 4319) and 1,25-dihydroxy-delta 16-23yne-vitamin D3 (1,25(OH)2-16ene-23yne-D3, Ro 23-7553) on cell growth was evaluated by determination of [3H]thymidine incorporation into DNA of human colon adenocarcinoma-derived Caco-2 cells. The extent of growth inhibition by the vitamin D compounds varied between 20-40% (at 10(-8) M), depending on particular growth conditions of Caco-2 cells as well as on the molecular structure of the vitamin D sterols. In confluent, i.e., rather quiescent cells, all three vitamin D compounds were equipotent in suppressing growth. In rapidly dividing log phase cells, 1,25(OH)2-16ene-23yne-D3 or 1,25,26(OH)3-22ene-D3 were ten or five times, respectively, more efficient than 1,25(OH)2D3. A substantial effect on induction of the colonocyte differentiation marker alkaline phosphatase was only elicited by 1,25(OH)2-16ene-23yne-D3. The ability of the vitamin D compounds to raise intestinal calcium absorption was evaluated by determination of 45Ca2+ accumulation in embryonic chick duodenal explants. In this assay, both synthetic analogs were less effective than 1,25(OH)2D3 by a factor of 20. The intrinsic bone resorbing activities of the vitamin D analogs were compared in organ-cultured neonatal mouse calvariae. The most effective antiproliferative compound, 1,25(OH)2-16ene-23yene-D3, stimulated calcium release from cultured bones at concentrations less than 10(-11) M, and was thus ten times more potent than 1,25(OH)2D3 and hundred times more than 1,25,26(OH)3-22ene-D3. PMID- 8446179 TI - Inhibition by 5-HT3 receptor antagonists of release of cholecystokinin-like immunoreactivity from the frontal cortex of freely moving rats. AB - Effects of the 5-HT3 receptor antagonists, ondansetron and tropisetron, on the release of cholecystokinin-like immunoreactivity (CCK-LI) in rat frontal cortex were investigated in conscious, unrestrained rats using intracerebral microdialysis. The release of CCK-LI was augmented by perfusion with 100 micrograms/ml veratrine and was fully Ca(2+)-dependent and tetrodotoxin sensitive. Ondansetron and tropisetron, each at 0.1-1 mumol/l, decreased concentration-dependently the veratrine-evoked efflux of CCK-LI. The reduction of CCK-LI output was approximately 30% when the antagonists were infused at 0.1 mumol/l. The data suggest that 5-HT3 receptor antagonists prevent the release of CCK evoked by endogenous 5-hydroxytryptamine. These drugs may thus represent a novel therapeutic approach in disease states, like anxiety, in which an inappropriately high release of brain CCK or 5-hydroxytryptamine seems to be involved. PMID- 8446181 TI - Pulsatile release of catecholamines in the hypothalamus of conscious rats. AB - To investigate the patterns of catecholamine release in the brain, the hypothalamus of conscious, freely moving rats was superfused through a push-pull cannula with artificial cerebrospinal fluid and the catecholamines dopamine, noradrenaline and adrenaline were determined in the superfusate radioenzymatically. Superfusate was continuously collected in time periods of 20 min for at least 20 h. Dopamine, noradrenaline and adrenaline release rates fluctuated according to an ultradian rhythm with a frequency of 1 cycle/92 min (dopamine and noradrenaline) or 99 min (adrenaline). Additionally, the three catecholamines were released according to an ultradian rhythm with the following frequencies: noradrenaline and adrenaline 1 cycle/12 h, dopamine 1 cycle/8 h. The release rates of dopamine and adrenaline were similar during light and dark periods, while the release rate of noradrenaline in the dark period was slightly lower than that during the light period. It is concluded that in the hypothalamus of the conscious rat the release rates of dopamine, noradrenaline and adrenaline fluctuate according to two ultradian rhythms with different frequencies. PMID- 8446180 TI - Catecholamine release in the locus coeruleus is modified by experimentally induced changes in haemodynamics. AB - The involvement of catecholaminergic neurons of the locus coeruleus in central cardiovascular control was investigated in the anaesthetized cat. Push-pull cannulae were bilaterally inserted into the LC and the release of noradrenaline and dopamine was determined radioenzymatically in the superfusate. The effects of experimentally induced changes in blood volume and vascular resistance on catecholamine release in the locus coeruleus were studied. Hypervolaemia strongly inhibited the release of noradrenaline in the locus coeruleus. Intravenous infusion of noradrenaline (5 micrograms.kg-1.min-1) elicited a pronounced pressor response which was also associated with a decrease in the release of noradrenaline in the locus coeruleus. Conversely, a fall of blood pressure caused by a controlled haemorrhage enhanced the release of noradrenaline. A profound fall in blood pressure caused by infusion of nitroprusside (8 micrograms.kg-1.min 1) did not modify the release rate of noradrenaline. Dopamine release rate was not significantly influenced by these cardiovascular alterations. The results demonstrate that increases in blood pressure elicited by vascular constriction or hypervolaemia inhibit the release of noradrenaline in the locus coeruleus. Decreases in blood pressure elicited by hypovolaemia enhance the release of noradrenaline, but lowering blood pressure by vasodilatation is ineffective. Hence, the release of endogenous noradrenaline in the locus coeruleus is responsive to haemodynamic signals, thus supporting the suggested integrative role of the locus coeruleus in central cardiovascular control. PMID- 8446182 TI - Cardiovascular and sympathoadrenal responses to intrathecal injection of neuropeptide K in the conscious rat. AB - In the conscious freely moving rat, the intrathecal (i.t.) injection of neuropeptide K (NPK; 0.65 to 6.5 nmol), at T-9 spinal cord level, produced dose dependent and prolonged (> 3 h) increases in mean arterial blood pressure (MAP) and heart rate (HR). The cardiovascular response to 3.25 nmol NPK was less sustained when injected at T-2 level. The cardiovascular response to 3.25 nmol NPK (T-9 level) was correlated with increases in plasma levels of noradrenaline, adrenaline and neuropeptide Y (NPY), and was significantly reduced by the prior i.v. administration of inhibitors of either alpha-adrenoceptors (1 mg/kg, phentolamine), alpha 1-adrenoceptors (1 mg/kg, prazosin), beta 1-adrenoceptors (1 mg/kg, metoprolol) or angiotensin converting enzyme (10 mg/kg, captopril). The cardiovascular response to NPK was also significantly reduced in rats that had undergone, 48 h earlier, bilateral adrenalectomy or to a greater extent sympathectomy with 6-hydroxydopamine. Whereas NPK-induced release of adrenaline was abolished by adrenalectomy, that of neuropeptide Y and noradrenaline was blunted by either treatment. The results suggest that the cardiovascular effect of i.t. NPK is mediated by the stimulation of the sympathoadrenal system and the release of angiotensin. Sympathetic fibers may play a greater role than the adrenal medulla in the cardiovascular response to NPK. It appears that neuropeptide Y derives from both sympathetic fibers and adrenal medullae. Hence, if released in the spinal cord, NPK may play an important role in cardiovascular and sympathoadrenal regulation. PMID- 8446183 TI - Activation of mesolimbic dopaminergic neurons following central administration of histamine is mediated by H1 receptors. AB - The effect of intracerebroventricular administration of histamine on the activity of mesolimbic and nigrostriatal dopaminergic (DA) neurons was determined in male rats. The activity of these neurons was estimated by measuring: (1) the accumulation of 3,4-dihydroxyphenylalanine (DOPA) after administration of a decarboxylase inhibitor, and (2) the concentration of 3,4-dihydroxyphenylacetic acid (DOPAC) in the nucleus accumbens and striatum, which contain the terminals of these neurons. Central administration of histamine increased both DOPA accumulation and DOPAC concentrations in the nucleus accumbens, but was without effect in the striatum. The increase in DOPAC concentrations in the nucleus accumbens occurred within 10 min and was sustained for at least 120 min. The H1 antagonist mepyramine blocked whereas the H2 antagonist zolantidine did not affect histamine-induced increases in DOPAC concentrations in the nucleus accumbens. Neither mepyramine nor zolantidine affected basal DOPAC concentrations in the nucleus accumbens. These results indicate that central administration of histamine stimulates mesolimbic DA neurons through an action at the H1 receptor, but has no effect upon the activity of nigrostriatal DA neurons. PMID- 8446184 TI - Changes in extracellular adenosine levels and population spike amplitude during graded hypoxia in the rat hippocampal slice. AB - Concentrations of adenosine and inosine in the incubation media of baths containing rat hippocampal slices were measured during graded hypoxia. Slices were exposed to atmospheres containing 95%, 71%, 48%, 24%, or 0% oxygen, with 5% CO2 and a balance of N2. Absorbance HPLC measurements were made with samples drawn from static tissue baths each containing four slices supported on a net at the interface between the medium and the atmosphere. Concentrations of adenosine and inosine were proportionate to the fractional oxygen content. They were significantly higher in atmospheres of 24% and 0% O2. Introducing a 95% N2/5% O2 atmosphere in place of 95% O2/5% CO2 resulted in a roughly 4-fold increase in the adenosine concentration in the bath. The adenosine transport blocker dipyridamole (200 microM), and the convulsant drug picrotoxinin (300 microM), had little effect on basal levels of adenosine measured at 95% O2 but significantly augmented the responses seen at 48%, 24% and 0% O2. Picrotoxinin, while increasing the adenosine concentration did not change the ratio of adenosine to inosine. In contrast, dipyridamole significantly increased the ratio of adenosine to inosine. Evoked population spikes were recorded from the CA1 layer. The population spike amplitude was depressed as the fractional oxygen content was reduced. It is concluded that adenosine regulation in the slice preparation is similar to that seen in the intact animal. In particular, the amounts of adenosine released into the incubation medium are related to oxygen availability. PMID- 8446185 TI - Efficacy of cerebroprotective substances in the management of functional disorders induced by the cytotoxic brain oedema-producing substance hexachlorophene. AB - The hexachlorophene-induced cytotoxic brain oedema is used as experimental model of brain damage, suitable for testing cerebroprotective substances. It has clinical importance since many brain injuries are accompanied by an oedema. The primary target of the neurotoxin, hexachlorophene, is the neuronal cell membrane, but it also causes secondary effects including a disruption of myelin lamellae, increases in water and sodium content, decreases of potassium content, and vacuolation in the white matter. Rats received orally hexachlorophene 240 mg/kg a day for three weeks by liquid diet. The disruption of coordinative motor response, observed in a specially developed test, was used to characterise hexachlorophene-induced injuries in studies designed to evaluate the potential of cerebroprotective substances. Because of their membranotropic efficacy some nootropic substances with different modes of action were examined. The disturbance of coordinative motor response was restored significantly earlier than in spontaneous remission following administration of piracetam, pyritinol, methyl glucamine orotate, naftidrofuryl, and also under the influence of the calcium antagonists cinnarizine, flunarizine and nifedipine. These results support the therapeutic use of nootropic substances in the management of neurotoxic injuries and brain oedema. PMID- 8446187 TI - Using information systems to track peritonitis rates. PMID- 8446186 TI - [3H]resiniferatoxin binding by the vanilloid receptor: species-related differences, effects of temperature and sulfhydryl reagents. AB - Specific binding of [3H]resiniferatoxin (RTX) is thought to represent the vanilloid (capsaicin) receptor. In the present study, we have used this binding assay to elucidate the contribution of differential receptor expression to the capsaicin-resistance of hamsters and rabbits; binding parameters were compared to those of species (rats, mice) regarded as capsaicin-sensitive. Whereas the 5-fold lower affinity for [3H]RTX binding in the hamster (100 pM) as compared to the rat (20 pM) is unlikely to account for the 100-fold difference in the in vivo responses of RTX-induced inflammation and hypothermia, the lack of detectable specific [3H]RTX binding sites in the rabbit might represent the predominant mechanism of capsaicin-resistance in this species. Regulation of the vanilloid receptor was further characterized in the rat. In accord with the temperature dependence of both in vivo and in vitro capsaicin actions, we found a marked temperature dependence for association rates. Dissociation turned out to have complex kinetics dependent on time and receptor occupancy. Low pH (5.5-7.0) did not affect receptor binding. Preincubation with heavy metal cations and other sulfhydryl-reactive agents inhibited specific [3H]RTX binding indicating that the vanilloid receptor is a thiol-protein, and that free sulfhydryl groups play an essential role in agonist binding activity. Preliminary characterization suggested noncompetitive inhibition. PMID- 8446188 TI - Tuberculosis and the HIV virus--a growing problem in health care. PMID- 8446189 TI - Concurrent total plasma exchange and hemodialysis. PMID- 8446190 TI - "The Tassin experience" gives a true picture of adequate dialysis. PMID- 8446191 TI - RAND/UCLA/Harvard study: inpatient dialysis costs increased after revisions to reimbursement coding. PMID- 8446192 TI - [A patient with hypocalcemia: an experiment of nature and culture]. PMID- 8446193 TI - [Non-surgical treatment of erection disorders]. PMID- 8446194 TI - [Home maintenance treatment with oxygen; the liquid oxygen system and other sources of oxygen]. PMID- 8446195 TI - [Granuloma inguinale (donovanosis): vigilance should be exercised]. PMID- 8446196 TI - [A study of the readers of the Nederlands Tijdschrift voor Geneeskunde]. PMID- 8446197 TI - [The readers of the Nederlands Tijdschrift voor Geneeskunde]. AB - In order to establish the reach, the reading frequency and the appreciation of the Nederlands Tijdschrift voor Geneeskunde, a telephone inquiry was conducted among a random sample of specialists, general practitioners, registrars and pharmacists in the Netherlands. The response amounted to 81.5% (n = 1515). Of the respondents, 94% received the Journal, and two-thirds read it every week. Eight out of ten saved the Journal, five even all volumes. The reading frequency varied greatly from one section to another. Of those who read the Journal at all, 74% always or often read the clinical lesson and 6% the original articles. Although, due to increasing specialization (in width and in depth), it is becoming increasingly difficult to satisfy all readers, the appreciation of the articles is high. PMID- 8446198 TI - [Managing psychogeriatric patients who stopped eating]. AB - We carried out a small survey among 22 interviewees working as physicians (n = 11) or as nurses (n = 11) in a nursing home. The questions concerned the last case they had seen of a psychogeriatric patient who did not eat any more, and the decision-making process. 35 patients were described to us: 13 in whom feeding was continued (mostly by drip) and 22 in which it was withheld. It appeared that the withholding of artificial feeding was the more common decision. If feeding was continued it was usually a time-limited trial. The decision-making process appeared to be careful and elaborate. Among the reasons to withhold feeding was the thought that the patient did not wish to live any more and was showing this by refusing to eat. Formal criteria for determining mental (in)competence were not used, however. When patients died after discontinuation of feeding, the dying process mostly was peaceful (15/17); five of the 22 patients in whom feeding was discontinued spontaneously resumed eating. PMID- 8446199 TI - [Experiences with intracavernous auto-injection for the treatment of erection disorders]. AB - We report on our experience with autoinjection therapy in 72 patients with erectile dysfunction. We analysed factors that have an impact on the outcome of autoinjection therapy, and we focused on psychological, sexological and relational issues. In 53 (74%) patients an organic aetiological factor was found. Although with the aid of injection 82% of the men were able to achieve an erection adequate for penetration, only 39% continued treatment beyond one year. Lowest drop-out rates were encountered among patients with diabetes mellitus and men without organic aetiology (50% and 53% respectively). The most important reason for discontinuation was lack of acceptance of autoinjection therapy by the partner. Other reasons were prolonged erection, haematomas, ineffectiveness and fear of self-injection. Although autoinjection provides a safe and effective long term method for the treatment of erectile dysfunction, the drop-out rate is strikingly high. Apparently, the acceptance of the partner is the most important determinant of the result of autoinjection therapy. Therefore, the partner should be involved in the counselling and treatment from the beginning. PMID- 8446200 TI - [Experiences with a vacuum apparatus in the treatment of erection disorders]. AB - The efficacy of two types of an external vacuum device designed to overcome erectile dysfunction was evaluated in 78 unselected patients. In 80% an organic aetiological factor was found. Although 77% of the men were able to achieve an erection adequate for penetration, only 46% continued treatment after 1 month. Among the reasons for discontinuation were ineffectiveness in 18 (23%), side effects in 7 (9%), recovery of spontaneous erection in 6 (8%), the time-consuming nature of the procedure 5 (6%), lack of acceptance of patient and partner 4 (5%), the high costs of the pump 2 (3%). The highest discontinuation rate was encountered in patients without signs of organic aetiology (81%). The device provides a non-invasive, reversible and safe alternative for the treatment of erectile dysfunction. It does not necessitate comprehensive aetiological assessment of erectile dysfunction. There are no differences between the results of vacuum device therapy (this study) and autoinjection therapy (the literature). The selection of patients who may profit by the vacuum device is enhanced if the patient is allowed to practice in his own private environment before purchasing the device. PMID- 8446201 TI - [Prenatal treatment of alloimmune thrombocytopenia using high-dosage IgG]. AB - Alloimmunization of the mother against foetal alloantigens can cause neonatal alloimmune thrombocytopenia (NAITP). The recurrence rate is high (90%). The thrombocytopenia in subsequent children is often more severe. Most feared are intracranial haemorrhages (ICH). Current diagnostics indicate that ICH often occurs in utero or during labour. Postnatal therapy is therefore of limited value. We treated three women who had had earlier newborns with severe NAITP, in 5 subsequent pregnancies with weekly high dose intravenous IgG from week 30-34. Four newborns of two women had no thrombocytopenia at birth. Only in one child was the NAITP as severe as in the previous affected sibling. We conclude that antenatal therapy with weekly high dose intravenous IgG is safe and often effective. In utero transfusions are indicated only in exceptional cases. PMID- 8446202 TI - [The physician as medical expert in legal procedures]. PMID- 8446203 TI - [Pregnancy and specialist education]. PMID- 8446204 TI - [Perinatal asphyxia and postpartum resuscitation: always starting, but when should it be stopped?]. PMID- 8446205 TI - [Medical activities under adverse conditions. In conclusion: to do it or not?]. PMID- 8446206 TI - [Subdural hematoma]. PMID- 8446207 TI - [Thinness is not always fashionable]. PMID- 8446208 TI - [Early stage carcinoma in Barrett esophagus; accidental finding or detective work?]. PMID- 8446209 TI - [High-dosage epinephrine in patients with cardiopulmonary arrest outside of the hospital?]. PMID- 8446210 TI - [Unsubstantiated concern over implanted silicone breast prostheses]. PMID- 8446211 TI - [Current viewpoints in the treatment of esophageal carcinoma]. PMID- 8446212 TI - [On which criteria are drug choices by hospital physicians based?]. PMID- 8446213 TI - [Farmacotherapeutisch Kompas 1993]. PMID- 8446214 TI - [Functioning of the tube stomach following esophagus resection for carcinoma]. AB - A retrospective study was made of the functional results of the tube stomach created in 80 patients after oesophageal resection because of carcinoma to restore the continuity. The study concerned patients who had survived the operation for longer than 18 months without indications of tumour recurrence or metastases and of whom clinical and endoscopical data of 3 months and one year after the operation were available. The functional results of the tube stomach may be regarded as good because one year postoperatively 86% of the patients were classified as excellent or very good according to the modified Visick classification. Dumping (18%), a sensation of fullness (26%) and diarrhoea (28%) were frequent complaints, occurring mostly soon after the operation. After one year these complaints are almost completely gone. Three months postoperatively, 19% of the patients had a stenosis of the anastomosis that required one or more dilatations. Reflux oesophagitis is the major late complication, leading to late stricture of the anastomosis. Reflux oesophagitis was encountered in 43% of the patients with an intrathoracic anastomosis and in only 6% of those with a cervical anastomosis; the difference is statistically significant. After one year, a stenosis due to reflux was encountered in four of the 30 patients (13%) with an intrathoracic anastomosis and in only one of the 50 patients (2%) with a cervical anastomosis. These results show that from the functional point of view, as well, the stomach is a good substitution organ after oesophageal resection, provided the anastomosis is created in the neck. PMID- 8446215 TI - [Are roentgen pictures of the skull indicated in patients with head injuries?]. PMID- 8446216 TI - [Hepatitis C; a new virus for an old disease]. PMID- 8446217 TI - [Malaria prophylaxis]. PMID- 8446218 TI - A comparison of clinical features of mycobacterial infections in young and elderly patients. AB - A comparison was made of the presentation of tuberculosis (TB) between a young immigrant population from Ethiopia (mean age 21.2 +/- 16 yr) and an elderly Israeli group (mean age 71.4 +/- 10 yr). Prominent differences were the complaint of weakness among the elderly who also had more anorexia and weight loss. The time between the onset of complaints and the diagnosis was 2 months in the elderly and 3.5 wk in the younger group (p < 0.05). Four of the elderly died, 2 from causes related to TB; none of the younger patients died. The insidious and non-specific symptoms in the elderly tend to cause a delay in the diagnosis unless there is a high index of suspicion. PMID- 8446219 TI - Two sisters with coeliac disease and jejunal cancer: just a coincidence? AB - Two sisters with asymptomatic coeliac disease are described; they both developed a primary jejunal cancer at the same age. While screening the family, a third sister was found to have coeliac disease, but without detectable cancer in the small intestine or stomach. These findings suggest an increased susceptibility in this family for carcinoma developing secondary to asymptomatic coeliac disease. We conclude that the finding in a patient of the combination of coeliac disease and malignancy in the digestive tract is sufficient reason to investigate the first-degree relatives with regard to the presence of coeliac disease and a secondary carcinoma. PMID- 8446220 TI - Panniculitis as the first manifestation of systemic lupus erythematosus: description of two cases. AB - Two patients are described in whom panniculitis proved to be the first symptom of the disease systemic lupus erythematosus (SLE). Histological examination of a painless solitary cutaneous lesion in the otherwise asymptomatic first patient showed a nonspecific nodular panniculitis; 1 yr later a definite diagnosis of SLE was made. In the second patient panniculitis had the clinical appearance of erythema nodosum and was one of several presenting symptoms of SLE. These patients were part of a group of 68 newly diagnosed patients with SLE, indicating a 3% prevalence of panniculitis in SLE. These cases illustrate that SLE should always be considered as an underlying disease in young female patients presenting with nodular panniculitis, which may mimic the clinical picture of erythema nodosum. PMID- 8446221 TI - Defects in insulin secretion in NIDDM: B-cell glucose insensitivity or glucose toxicity? AB - In NIDDM, first-phase insulin release to glucose is (almost) absent. However, in contrast to older studies which suggested that in NIDDM the B-cell is "blind" for glucose, recent evidence indicates that the B-cell is not insensitive for glucose as far as second phase release is concerned. This suggests that the metabolism of glucose is probably not deranged in NIDDM, since glucose leads to insulin release after it has been metabolized. Hyperglycaemia itself has a deleterious effect on insulin release, so-called glucose toxicity. Various mechanisms have been proposed, whereby hyperglycaemia may diminish insulin release: inhibition of Ca2+ mobilization from the endoplasmic reticulum by glucose-6-phosphate, Ca2+ uptake in the ER by glucose and inhibitory effects of protein kinase C. Whatever may prove to be the underlying mechanism(s), glucose toxicity is unlikely to be the only cause of insulin secretory disturbances in NIDDM, since the glucose level would have to be elevated before it could be toxic. Non-insulin-dependent diabetes mellitus (NIDDM) is characterized by both defects in insulin action and insulin secretion. With regard to the defects in insulin release, much research has originated from two (partly) opposing hypotheses, namely the presence of pancreatic B-cell glucose blindness and the hypothesis of pancreatic B-cell glucose toxicity in NIDDM. PMID- 8446222 TI - The familial hyperchylomicronaemia syndrome. AB - The familial hyperchylomicronaemia syndrome is a hereditary disorder of lipoprotein metabolism caused by lipoprotein lipase (LPL) deficiency, apolipoprotein(apo) CII deficiency or LPL inhibition. This syndrome, which is characterized by hyperchylomicronaemia, attacks of epigastric pain, recurrent pancreatitis and the presence of eruptive xanthomas, may ultimately lead to necrotizing pancreatitis or pancreatic insufficiency. Treatment consists of lifelong adherence to a low-fat diet to prevent hyperchylomicronaemia and its sequelae. We describe here the clinical course of a patient with acute pancreatitis due to hyperchylomicronaemia based on hereditary LPL deficiency. The different causes of the familial hyperchylomicronaemia syndrome and its therapy will be discussed and an update is presented of our knowledge concerning the basic molecular defects of this hereditary disorder. PMID- 8446223 TI - Erythropoietin versus iron chelators in anaemia and iron overload. PMID- 8446224 TI - The relationship between serum triiodothyronine and thyroxine concentrations in hyperthyroidism. AB - In toxic nodular goitre relapses of hyperthyroidism after medical therapy probably are more common than in toxic diffuse goitre. It has also been reported that in patients with toxic diffuse goitre a high ratio of triiodothyronine (T3) and thyroxine (T4), initially or during medical treatment, predicts a relapse of the hyperthyroidism after cessation of therapy. We therefore studied the relationship between T3 and T4 in untreated patients with toxic diffuse goitres (n = 46, mean ratio T3/T4 29.6 nmol/mumol +/- 10.7 SD) and toxic nodular goitres (n = 12, ratio 29.3 +/- 17.1), and found no significant difference. Both groups differ significantly from normal controls (n = 16, ratio 14.6 +/- 1.5, P < 0.01). From the patients with toxic diffuse goitres we compared two groups. Patients in the first group remained in remission after short-term medical treatment (n = 10); the second group contains patients with a relapse of hyperthyroidism (n = 10). Differences between both groups in the median ratio of T3 and T4 were assessed before the start of treatment, at 4 and at 8 weeks. No significant differences were found between the two groups. The ratio of T3 and T4 is not helpful in distinguishing diffuse and multinodular toxic goitre or in determining the prognosis after medical treatment of hyperthyroidism caused by a hyperfunctioning thyroid gland. However, recurrence of hyperthyroidism was found in 3 patients with a T3/T4 ratio > 60 nmol/mumol after 8 weeks of treatment. PMID- 8446225 TI - Villous tumours of the duodenum. An analysis of the literature with emphasis on malignant transformation. AB - Until 1992, 192 patients with a villous tumour of the duodenum have been reported. The symptoms and signs of this tumour are mostly related to obstruction of the duodenal lumen or bile ducts. Radiological examination (e.g., hypotonic duodenography) may be of some help in diagnosing a villous tumour of the duodenum. In histological specimens, superficial parts of the tumour may appear benign while deeper parts may contain adenocarcinoma. Therefore, endoscopy with multiple biopsies or the use of electrocautery for removal of large fragments of the tumour should play a major role in obtaining an accurate preoperative diagnosis. Forty-two per cent of all reported villous tumours showed malignant changes at the time of presentation. Because of this great risk of malignant transformation, these tumours should always be resected. Unlike large bowel mucosa, small bowel mucosa contains lymphatics that course through the villi extending near the luminal surface, suggesting the possibility of early lymphatic spread before invading the muscularis mucosae. In 24 patients with intramucosal carcinoma, however, no metastases were found. For this reason, a mucosal resection of these tumours would appear to be an effective and safe treatment. Invasive carcinomas or recurrent villous tumours require more radical surgery. Depending on histological evaluation, location in the duodenum and intraoperative findings, segmental resection of the villous tumour or pancreaticoduodenectomy would seem to be an appropriate surgical procedure. A pedunculated villous tumour may be removed endoscopically. It is recommended that all patients who had their tumour resected locally, should be surveyed endoscopically. PMID- 8446226 TI - Analysis of the Afrikaner mutation in exon 9 of the low-density lipoprotein receptor gene in a large Dutch kindred suffering from familial hypercholesterolaemia. AB - Familial hypercholesterolaemia (FH) is the most common genetic metabolic disorder, affecting about 1 in 500 persons in the general population. With novel techniques, it is possible to identify the molecular defects underlying FH in the gene coding for the low-density lipoprotein (LDL) receptor, thereby confirming the diagnosis of FH. In this study we present a large family with a specific mutation in exon 9 of the LDL-receptor gene (an Afrikaner mutation) and we demonstrate that by a large-scale case-finding study in this family, carriers of such a mutation can be detected. Of 63 family members, 13 were shown to be at risk for cardiovascular disease as judged by their lipoprotein profile or the presence of the Afrikaner mutation. Two persons were detected, affected with a dyslipidaemia other than FH. Medical management was initiated in order to reduce the high cardiovascular risk associated with this disorder. PMID- 8446227 TI - Acute renal failure in theophylline poisoning. AB - A 57-yr-old woman with an intentional theophylline overdose complicated by rhabdomyolysis, renal failure and microangiopathic haemolytic anaemia is reported. Severe renal vasoconstriction, myoglobinuria and antagonism of adenosine are considered to be the principal pathophysiological renal mechanisms involved. PMID- 8446228 TI - Acute right ventricular heart failure in a patient with renal cell carcinoma after interferon therapy. AB - In a patient with diffuse pulmonary metastases of a renal cell carcinoma the development of severe pulmonary hypertension is described after reaching a complete remission during treatment with r-IFN-alpha 2c and rIFN-gamma. Rechallenge with interferon after the discovery of recurrent disease did not lead to deterioration of the cardiopulmonary condition. Possible causative mechanisms are discussed. PMID- 8446229 TI - A rare cause of a hepatic abscess: diverticulitis of the ileum. AB - A 41-year-old man with a hepatic abscess due to diverticulitis of the ileum is presented. Drainage of the hepatic abscess and antibiotic therapy resulted in complete recovery. The literature on small bowel diverticulitis and its complications is reviewed. Hepatic abscess is a very rare complication. To our knowledge this is the second case to be described in the literature. PMID- 8446230 TI - The role of Helicobacter pylori in non-ulcer dyspepsia and gastritis. AB - A review is presented on the relationship between Helicobacter pylori infection and gastritis and its possible significance in non-ulcer dyspepsia. Although there is consensus about the pathogenetic role of H. pylori in gastritis, the correlation between H. pylori and gastritis does not appear to be qualitative, as generally thought and accepted, but rather quantitative. It is not a black and white relationship; in other words the microorganism is present in large quantities in inflamed tissue but is also present in normal healthy mucosa in low numbers. The hypothesis is proposed of an equilibrium between virulence of H. pylori on the one hand and mucosal defence mechanism on the other hand. Distortion could lead to an attack of gastritis. The present view is that the bacterium is neither commensal nor pathogen, but is able to change its role depending on the local and momentary situation. Given the presence of H. pylori infection in patients with non-ulcer dyspepsia, with or without gastritis, the significance of the infection is probably greater than thought. PMID- 8446231 TI - Stereoisomerism in drug therapy. PMID- 8446232 TI - Biological significance of atrial natriuretic peptide in the kidney. AB - In summary, ANP exerts its action in the kidney directly and indirectly. Its qualitative importance in body fluid regulation remains unsettled. It appears that its role is more important in pathophysiological conditions such as CHF in which plasma ANP is elevated. Paradoxically, kidneys in heart failure, nephrosis and diabetes are characterized by diminished responsiveness to exogenous ANP. Further studies are needed to ascertain whether this involves an alteration at the receptor or postreceptor site. The cellular mechanisms for receptor regulation and postreceptor signalling in physiology and pathophysiology need further investigation. Finally, a paracrine mode for the action of ANP and other natriuretic peptides has been proposed. Whether they act locally to facilitate sodium excretion and how much importance they have compared to circulating ANP remain to be clarified. The potential role of ANP as a growth inhibitor is also intriguing. PMID- 8446233 TI - Glomerulocystic kidney disease: a single entity? AB - A case of glomerulocystic disease in a young adult with no family history or presence of other extrarenal malformations is described. Histological study revealed the presence of numerous cortical cysts corresponding to dilatations of Bowman's space. The patient had mild stable chronic renal failure for 5 years. In our patient, the disease corresponded to a sporadic adult form of glomerulocystic disease. PMID- 8446234 TI - Piridoxilate-induced oxalate nephropathy can lead to end-stage renal failure. AB - A 71-year-old woman was admitted with end-stage renal failure and histological evidence of oxalosis. This case of diffuse renal tubular crystal calcium oxalate deposits seems to be induced by long-term piridoxilate therapy (10 years) or simultaneous intake of both piridoxilate and vitamin C (500 mg/day for 6 months), since no other cause of secondary oxalosis could be found. So, it seems necessary to monitor the serum creatinine level, especially in the elderly, during piridoxilate therapy and to avoid high vitamin C intakes in patients under such treatment to prevent development of renal insufficiency. PMID- 8446235 TI - Cystic basement membrane with increased negative charge in rat autosomal recessive polycystic kidney. PMID- 8446236 TI - Acute cardiac overload secondary to aortocaval fistula effectively treated with continuous hemofiltration. PMID- 8446237 TI - Correlation between glomerular injuries and the existence of cytokines in glomeruli of patients with IgA nephropathy. PMID- 8446238 TI - TNF inhibitory activity in the urine of chronic renal failure patients with glomerulonephritis. PMID- 8446239 TI - Subcutaneous versus intravenous recombinant human erythropoietin administration in hemodialysis patients. PMID- 8446240 TI - Hepatitis C transmission in dialysis. PMID- 8446241 TI - Sudden hearing loss in a cyclosporin-treated renal transplantation patient. PMID- 8446242 TI - High-dose methylprednisolone inhibits the OKT3-induced cytokine-related syndrome. PMID- 8446243 TI - Calcium acetate versus calcium carbonate as phosphate binders. PMID- 8446244 TI - Nonamyloidotic fibrillar glomerulopathy and rheumatoid arthritis. PMID- 8446245 TI - In advanced renal failure, dietary phosphorus restriction reverses hyperparathyroidism independent of changes in the levels of calcitriol. PMID- 8446246 TI - Perfusion pressure, proteinuria and the isolated rat kidney--comment. PMID- 8446247 TI - Effect of phosphatidylcholine on the function of human mesothelial cells in vitro. AB - We tested the hypothesis that phosphatidylcholine (PC) molecules present in the dialysis solution may interact with the mesothelial cell membrane and modify its function. In vitro experiments were performed on human mesothelial cells (HMC) in culture. PC decreased proliferation of HMC when used at concentrations of 200 mg/l and higher. PC was also cytotoxic to HMC as measured by the release of lactate dehydrogenase from their cytosol. Cells exposed to PC had a diminished capacity for taking up 86Rb from medium. PC decreased the fibrinolytic properties of HMC and increased their procoagulant activity. Our results suggest that the positive short-term effect of the addition of PC to the dialysis solution (i.e., an increase in ultrafiltration) may be over-shadowed by its deleterious action on HMC membrane. PMID- 8446248 TI - Prognosis of acute tubular necrosis: an extended prospectively contrasted study. AB - The ability to predict the outcome in acute tubular necrosis (ATN) remains elusive despite considerable efforts. Accurate prediction is a crucial priority and has large economical and ethical implications, mainly to judge when treatment is futile and further efforts only prolong miserable agony. To analyze the influence of risk factors in the prognosis of ATN, we applied, in an initial phase, a prospective protocol of demographic data, cause of renal failure, diuresis, need of dialysis and clinical conditions in 228 patients using multiple linear and logistic regression models. In a control phase with 100 consecutive patients, we checked the accuracy of the results previously obtained, evaluating further the overall population of 328 patients in a synthetic phase. Finally, the validation of the equations obtained was verified in 25 patients from another hospital. As a complement of this 4-phase study, detailed statistical comparisons between both linear and logistic multiple regression models were undertaken. Correlation between probability of death obtained with equations from the initial phase applied to control patients and real evolution of these patients, survival or death, was excellent. The study of the synthetic phase revealed coma, assisted respiration, hypotension, oliguria and jaundice as having an independent positive influence on mortality and nephrotoxic etiology and normal consciousness on good prognosis. For the linear model, the same cut-off point of discriminant score (0.9) above which there were no chances for survival could be established in the 4 phases. With the logistic model, it only was found at later phases. The multiple linear was better than the logistic regression model in terms of better correlation with real mortality, better sensitivity and specificity intervals, easier use of discriminant cut-off point and better adjustment of distribution of standardized residuals to expected normal function. Early prognosis of ATN is possible and can be given using simple clinical features. A discriminant score allows to distinguish patients without chances for survival. The multiple linear is better than the logistic regression model in the prediction of the outcome in ATN. PMID- 8446249 TI - Heterogeneity in peritoneal transport during continuous ambulatory peritoneal dialysis and its impact on ultrafiltration, loss of macromolecules and plasma level of proteins, lipids and lipoproteins. AB - We investigated the effect of heterogeneity in the peritoneal transport of plasma proteins on dialysis efficiency and plasma levels of proteins, lipids and lipoproteins in 32 patients undergoing long-term continuous ambulatory peritoneal dialysis (CAPD; 9 females and 23 males, 18-76 years old). Eleven patients were studied on several occasions (at 0-42 months) and the remainder at 6-60 months on CAPD (n = 49). We have divided our patients arbitrarily into two equal groups according to their protein concentration in the peritoneal effluent at the end of an 8-hour cycle. Patients with a high peritoneal protein concentration (> or = 2 g/l/1.73 m2) have lower ultrafiltration capacity, higher glucose absorption rate and increased loss of most plasma proteins [including albumin, immunoglobulins (Ig), complement components and high-density lipoproteins (HDL)] compared to patients with a low peritoneal protein concentration (< 2 g/l/1.73 m2). Consequently, plasma levels of albumin, IgM and HDL were lower in patients with a high peritoneal protein concentration. The latter had also increased levels of plasma triglycerides and very-low-density lipoproteins. The difference observed in peritoneal transport between the groups could be ascribed only in part to the duration of CAPD treatment, and hence to the number of peritonitis episodes but not to medications. Therefore, we suggest that inherent constitutional factors may be responsible for some of the observed heterogeneity in the peritoneal transport of these patients which is already evident at the start of CAPD treatment. Patients with high peritoneal transport are exposed to an augmented atherogenic plasma lipid profile in addition to a reduction in dialysis efficiency (ultrafiltration failure). These patients may become prone also to nutritional and immunological disturbances. Therefore, we suggest taking these effects into consideration before choosing the appropriate dialysis modality in patients with increased peritoneal transport for plasma proteins. PMID- 8446250 TI - Glucose-induced insulin secretion in uremia: relation with acid-base balance and effects of bicarbonate administration. AB - In order to evaluate effects of metabolic acidosis on glucose metabolism in uremia, we studied, by an intravenous glucose tolerance test (IVGTT), 46 patients with severe chronic renal failure divided into three groups according to their blood bicarbonate (BB) values: group A formed by 15 patients without or with light metabolic acidosis (BB > or = 20 mEq/1); group B formed by 18 patients with moderate metabolic acidosis (16 < or = BB < 20 mEq/1); group C formed by 13 patients with severe metabolic acidosis (BB < 16 mEq/1). In 8 patients of group B (subgroup B1) and in 8 of group C (subgroup C1), IVGTT was also repeated after adjustment of acid-base balance by intravenous or oral bicarbonate administration. Twenty-nine healthy volunteers formed the normal controls. For each test, glucose constant decay (K), immunoreactive insulin (IRI) area and C peptide (C-p) area response, insulinogenic index (IGI) and insulin resistance index (RI) were calculated. Compared to controls, all uremic groups showed significantly lower values of K and IGI and significantly higher values of C-p area and RI. In group C, RI was significantly higher than in groups A and B. No differences were found in the other glucose metabolism parameters among the uremic groups. After bicarbonate administration, subgroup C1 showed a significant decrease in RI and a rise in K values, while subgroup B1 showed no changes in glucose metabolism parameters. From these data, we infer that abnormalities of acid-base balance do not affect insulin response but severe metabolic acidosis may play an additional role in the insulin resistance of uremic patients. PMID- 8446251 TI - Renal prostaglandins and thromboxane A2 lack a functional significance in the genesis of protein-induced glomerular hyperfiltration in human renal disease. AB - The study was devised to assess the effects of a protein load (2 g/kg BW) on urinary prostaglandin E2 (PGE2), 6-keto-PGF1 alpha and thromboxane A2 (TxA2) in patients with renal failure of glomerular origin. To this end, 8 women with a glomerular filtration rate of 55 +/- 12 ml/min x 1.73 m2 underwent the following studies: study 1: control; study 2: meat meal; study 3: meat meal+intravenous aspirin; study 4: pretreatment with oral aspirin for 2 days+protocol in study 3. Glomerular hyperfiltration was seen after the meat meal (study 2) and was not suppressed by aspirin (studies 3 and 4). Urinary PGE2, 6-keto-PGF1 alpha and TxA2 increased after the meat meal in study 2 and were suppressed by aspirin in studies 3 and 4. The ratio between vasodilative (PGE2 + 6-keto-PGF1 alpha) and vasoconstrictive (TxA2) autacoids increased during the meat meal (study 2) and was suppressed when aspirin was injected at the time of the oral protein load, thus, the effect of aspirin was much greater for PGE2 and PGF1 alpha than for TxA2. These data do not support that urinary prostaglandin and TxA2 have a direct role in renal hyperfiltration due to an acute protein load. PMID- 8446252 TI - Screening for congenital renovascular hypoplasia and renal artery stenosis by acute converting enzyme inhibition. AB - To evaluate the usefulness of the captopril test for identifying renal artery stenosis (RAS) and renovascular hypoplasia (RAH), we studied 48 hypertensive patients. In 20 hypertensives with screening procedures indicating renovascular disease and in 28 essential hypertensives (EH), the plasma renin activity (PRA) responses to an oral test dose of captopril (50 mg) were studied. A 60-min post captopril PRA increase of 150% (or 400% if baseline PRA < or = 3 ng/ml/h) was considered as positive. Renal angiography was performed in all cases. Among the 20 renovascular hypertensive patients, RAH in 9 and RAS in 11 subjects were proved by angiography. The captopril test in all patients with RAH resulted negative (mean PRA increase 50%); furthermore, the test identified 7 of the 11 RAS (mean PRA increase 477.6%); sensitivity and specificity for RAS were 64 and 88.8%, respectively. In the EH group, there were 3 false-positive subjects (mean PRA increase 122%). This study demonstrates that the PRA responses to a test dose of captopril are a useful screening test for distinguishing RAH from RAS, and for identifying the latter in hypertensive patients. These data also suggest that in subjects with RAH, hypertensive disease may not renin dependent. PMID- 8446253 TI - Hepatitis B virus deoxyribonucleic acid in kidney cells probably leading to viral pathogenesis among hepatitis B virus associated membranous nephropathy patients. AB - In order to investigate the role of hepatitis B virus (HBV) DNA in the pathogenesis of renal lesion in HBV-associated membranous nephropathy (HBVMN) patients, serial studies using an in situ hybridization technique at different time points were performed. Within 6 months after the onset of the disease, 7 of 8 (87.5%) HBVMN patients demonstrated HBV DNA in the glomeruli and tubular epithelia. In contrast to the 14 HBVMN specimens taken later than 6 months after the onset, HBV DNA was detectable in only 3 (21%) in the tubular epithelia but none in the glomerular region. Most of the glomeruli-associated HBV DNA seemed extracellular because they were also positive for both the accumulation of HB e antigen (HBeAg)-anti-HBe antibody (Ab) immune complex and immunoglobulin G. The finding suggested that glomeruli-associated viral DNA is joined with filtered HBeAg-anti-HBeAb immune complexes. In the analysis of follow-up biopsies, HBV DNA in tubular epithelia was detected more frequently in the progressive group (50%) than in the nonprogressive group (0%). HBV DNA was detectable in the tubular epithelia in 2 cases who were progressing to end-stage renal disease and had heavy proteinuria. However, in the cases with mild or no proteinuria, HBV DNA was no longer detectable in the kidney. These findings suggest that HBV disseminates in the kidney and its dynamic changes at different time points may implicate the important role of HBV in the pathogenesis of HBVMN. This needs further study to be clarified. PMID- 8446254 TI - Antibiotics and energy delivery to the phagocytosis-associated respiratory burst in chronic hemodialysis patients: a comparison of cefodizime and cotrimoxazole. AB - Twenty-three stabilized chronic uremic patients with no active or recent infection were treated for 10 days with either cefodizime (5 x 2 g intravenously, n = 10) or cotrimoxazole (960 mg orally b.i.d., n = 8) in order to evaluate the effects on the depressed polymorphonuclear metabolic response to phagocytic challenge; a separate group of 5 patients received placebo. Ex vivo evaluation in whole blood of energy delivery to the phagocytosis-associated respiratory burst activity in response to latex and zymosan challenge was determined by measuring hexose-monophosphate shunt NAD(P)H-oxidase-related glycolytic activity. Cefodizime induced a statistically significant increase in the baseline-depressed glycolytic response for both latex and zymosan challenge, in contrast to cotrimoxazole and placebo. Depressed phagocytosis-related metabolic function in hemodialyzed patients was stimulated by cefodizime in recommended therapeutic doses but not by cotrimoxazole, the effect persisting for at least 2 weeks after the end of treatment. PMID- 8446255 TI - Urine transforming growth factor-beta activity is related to the degree of scarring in crescentic nephritis in the rabbit. AB - Crescentic nephritis was induced in rabbits by injection of antirabbit glomerular basement membrane (GBM) antibodies. Urine samples were obtained by catheterization and assayed for transforming growth factor-beta (TGF-beta) activity. On day 31, all animals were sacrificed for evaluation of renal cortical histopathology and collagen content. The results show that control rabbit urine contains measurable amounts of TGF-beta. Urine TGF-beta activity was expressed in relation to urine creatinine concentration to correct for variation in urine concentration. When expressed in this manner, urine TGF-beta activity increased from day 2 onwards, peaked on day 7 and returned to normal levels after day 14. This time course is identical to that previously seen for the cortical and glomerular production of TGF-beta in the same model. Furthermore, when the normalized TGF-beta values for each animal were compared to their respective fibrosis parameters on day 31, significant correlations were observed for the values of urine TGF-beta activities on day 7 and all indices of fibrosis. These results suggest that measurements of urine TGF-beta activity at certain critical stages of disease could be useful in predicting the progression to end-stage renal disease with fibrosis and might serve as a helpful noninvasive adjunct in monitoring response to therapy. PMID- 8446256 TI - Progression of chronic adriamycin nephropathy in leukopenic rats. AB - In this study, we examined the progression of chronic Adriamycin (ADR) nephropathy in mild leukopenic rats and tried to define the possible relationship between tubulointerstitial lesions and proteinuria in this model. Chronic ADR nephropathy was induced by 2 doses of ADR (2 mg/kg) in 32 Sprague-Dawley rats. Eight of these were randomly assigned to cyclophosphamide treatment (50 mg/kg), given intravenously every week, to keep the blood leukocyte count constantly lower than 5,000/mm3. Serial parameters were followed for 16 weeks including clearance studies with iothalamate and p-aminohippurate and the analysis of urinary protein composition by: (a) an enzymatic assay for beta-glucosidase; (b) specific ELISA using antibodies against rat albumin and RBP, and finally (c) two dimensional electrophoresis. ADR-treated rats rapidly (within 2 weeks) developed massive proteinuria which was in constant increment throughout the disease evolution in each single component (i.e., high and low molecular weight proteinuria, enzymuria) and developed renal insufficiency. At week 8, in ADR rats, glomerulosclerosis was mild whereas tubulointerstitial infiltrates predominated, characterized mainly by CD4+ T lymphocytes while CD8+ T lymphocytes were inconspicuous, and macrophages were only occasionally present. All such alterations had worsened after 16 weeks when the tubulointerstitial infiltration was associated with marked interstitial fibrosis and tubular atrophy. Leukopenia induced by cyclophosphamide was in all cases associated with a net amelioration of renal histopathology reducing tubulointerstitial infiltrates (by 40%) and glomerulosclerosis (33 +/- 5 vs. 52.2 +/- 7.5% sclerotic glomeruli) and also ameliorated glomerular filtration indexes (Cl 780 +/- 40 vs. 447 +/- 66 microliters/min/kg-1). In spite of these differences, albuminuria and urinary retinol-binding protein were comparable at weeks 4, 8 and 16 in this group, while urinary beta-glucosidase was decreased at week 16 (p < 0.001) in cyclophosphamide treated rats. No other qualitative changes in urinary proteins were detectable by 2-dimensional electrophoresis during the disease development. We concluded that chronic leukopenia prevents interstitial cellular infiltration by lymphocytes, interstitial fibrosis and slows down the decline of renal function typical of chronic ADR nephropathy. Glomerulosclerosis is also reduced in leukopenic rats without any appreciable changes in the urinary excretion of high molecular weight proteins deriving from the glomerulus. Finally, the improvement in tubulointerstitial alteration is associated with the reduction in urinary lysosomal enzymes. Tubulointerstitial alterations are implicated with a prominent role in the progression towards renal failure in chronic ADR glomerulopathy. PMID- 8446257 TI - Elevation of plasma angiotensinogen in rats with experimentally induced nephrosis. AB - In order to determine the activity of the renin-angiotensin system in the nephrotic syndrome, the plasma concentration of angiotensinogen was measured in rats with puromycin aminonucleoside (PA)-induced nephrosis using two different methods: a direct radioimmunoassay, which measures both angiotensinogen and des angiotensin I-angiotensinogen, and an indirect assay, which measures angiotensin I liberated from angiotensinogen by excess renin. The plasma concentration of angiotensinogen as measured by the direct assay increased before the appearance of PA-induced hypoproteinemia or proteinuria and subsequently decreased to normal levels simultaneously with the appearance of proteinuria. The indirect assay of angiotensinogen also demonstrated an increased concentration of plasma angiotensinogen before the development of nephrosis, but the level decreased to below normal after the appearance of proteinuria. Both plasma renin concentration and renin activity also increased simultaneously with the increase in plasma angiotensinogen. The difference between the concentrations of plasma angiotensinogen determined by these methods increased before and during the early phase of PA-induced nephrosis, suggesting the increased consumption of angiotensinogen by renin during this period. Measurement of plasma corticosterone and serum interleukin-6 revealed that these circulating factors were not involved in the elevation of plasma angiotensinogen in rats with PA-induced nephrosis. These results indicate that the renin-angiotensin system is activated before the appearance of PA-induced nephrotic syndrome. PMID- 8446258 TI - Induction of gelatinolytic neutral proteinase secretion by lipid peroxide in cultured mesangial cells. AB - To investigate whether lipid peroxides in tissue and/or blood play an important role in the injury to mesangial cells and glomerular structural proteins, we studied the effect of linoleic acid hydroperoxide (LHO) on mesangial cells cultured from rat kidneys. When 1.0-3.0 nmol/ml of LHO were added to the culture, the production of 70-kDa gelatinolytic neutral proteinase by mesangial cells was enhanced without morphological damage. The production of the enzyme, however, was inhibited by an addition of 4.0 or 5.0 nmol/ml of LHO and a microscopic examination also demonstrated marked injury to mesangial cells in the presence of these concentrations of LHO. These data suggest that there is a possibility that increased lipid peroxides in tissue and/or blood play a role in the injury to mesangial cells and glomerular structural proteins leading to mesangiopathy. PMID- 8446259 TI - Membranous nephropathy and thromboembolism: is prophylactic anticoagulation warranted? PMID- 8446260 TI - Does serum creatinine rise faster in rhabdomyolysis? PMID- 8446261 TI - Long-term (6 months) cross-over comparison of calcium acetate with calcium carbonate as phosphate binder. AB - A previous short-term study of 10 weeks in 8 patients had shown us that with half the dose of elemental calcium, calcium acetate (CaAc) could control predialysis plasma phosphate (PPO4) as well as calcium carbonate (CaCO3) but that the incidence of hypercalcemia was not decreased. To better appreciate the value of CaAc in comparison to CaCO3, CaAc was given to 28 patients on chronic hemodialysis (6 men, 22 women, age 61 +/- 14 years; dialyzate Ca:1.5 mmol/l) for 6 months to replace CaCO3 at half the dose of elemental calcium (1,235 +/- 521 versus 2,375 +/- 1,470 mg/day). Because of gastrointestinal intolerance, CaAc had to be discontinued in 5 patients after 1-5 months. Magnesium hydroxide [Mg(OH)2] given in 18 of them in association with CaCO3 was discontinued and reintroduced in 6 patients in order to keep PPO4 < 2 mmol/l. Mean dosage of Mg(OH)2 was 2.09 +/- 1.4 g/day with CaCO3 and 0.9 +/- 0.5 with CaAc. Predialysis plasma concentrations of calcium and phosphate were monitored weekly during the 3 months of the control period under CaCO3 and during the 6-month administration of CaAc. Plasma calcium (PCa) was comparable with the 2 treatments (2.47 +/- 0.11 vs. 2.5 +/- 0.10 mmol/l), but PPO4 was significantly lower with CaAc (1.82 +/- 0.26 vs. 1.73 +/- 0.23 mmol/l). Plasma alkaline phosphatase remained constant (122 +/- 66 vs. 122 +/- 70; normal < 170 UI/l) as well as plasma intact PTH (121 +/- 153 vs. 121 +/- 146; normal < 54 pg/ml) and plasma aluminum (0.34 +/- 0.23 vs. 0.32 +/- 0.20 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446262 TI - Comparison of fine-needle aspiration biopsy, Doppler ultrasound, and radionuclide scintigraphy in the diagnosis of acute allograft dysfunction in renal transplant recipients: sensitivity, specificity, and cost analysis. AB - 150 episodes of allograft dysfunction in 128 renal transplant recipients, 77 due to acute rejection, 32 secondary to acute-on-chronic rejection, 33 due to either prerenal factors, acute tubular necrosis, or ciclosporin A nephrotoxicity, and 8 secondary to multiple causes, were evaluated by fine-needle aspiration biopsy (FNAB), Doppler ultrasound (DUS), and radionuclide scintigraphy (RS), each performed within a 24-hour period and prior to any specific therapeutic intervention. Tests were interpreted by appropriate specialists in a large transplant center without access to clinical information. The final diagnosis was based primarily upon response to therapeutic maneuvers with histological (core biopsy) confirmation in 123 episodes. RS was the most sensitive (70%) test for the diagnosis of acute rejection during the early posttransplant period, exceeding both FNAB (52%) and DUS (43%). The predictive accuracy of either FNAB, DUS, RS, or core biopsy in the detection of a steroid-responsive component to acute rejection when superimposed upon chronic rejection was low at approximately 50%. When the underlying cause of renal dysfunction was either prerenal, acute tubular necrosis, or ciclosporin A nephrotoxicity, FNAB, DUS, and RS each gave an erroneous diagnosis of acute rejection in about 50% of the episodes. Cost analysis revealed that core biopsy was the most expensive test, but only 9% more than RS, with FNAB the least costly. In conclusion, the lack of ideal sensitivity and specificity combined with the expense of present-day FNAB, DUS, RS, and core biopsy in the diagnosis of a therapeutically reversible component to acute-on chronic rejection and of FNAB, DUS, and RS in the diagnosis of acute rejection during the early posttransplant period should prompt research into ways to improve their diagnostic yield or alternate modalities. PMID- 8446263 TI - Plasma parameters of the prothrombotic state in chronic uremia. AB - We measured plasma parameters of the prothrombotic state, namely thrombin antithrombin III complex (TAT), fibrinopeptide A (FPA). D-dimer (DD), von Willebrand factor (vWF), tissue-type plasminogen activator (tPA), beta thromboglobulin (beta TG), platelet factor 4 (PF4) and serotonin (5HT) in a series of 51 adult patients with chronic uremia: 22 were on maintenance hemodialysis (MHD) and 29 on conservative dietary treatment. Serum tumor necrosis factor alpha (TNF) was determined as well. Uremics presented significantly higher levels of TAT, FPA, DD, vWF, TNF, beta TG and 5HT than normal controls. Patients on conservative treatment showed lower levels of TAT, DD, TNF and beta TG than patients on MHD. Our results provide evidence that a prothrombotic state exists in chronic uremia and that MHD patients have a higher degree of hypercoagulation. Both hemodialysis procedure and uremia-related factors are likely to contribute to the hemostatic derangement. PMID- 8446264 TI - Apolipoprotein-B-containing lipoproteins and the progression of renal insufficiency. AB - Hyperlipidemia is associated with accelerated glomerular sclerosis in experimental renal insufficiency. To investigate whether the dyslipoproteinemia seen in human renal failure also influences the future course of renal insufficiency, we have correlated plasma levels of lipids and apolipoproteins at start of follow-up with the subsequent change in renal function in 34 adult patients with chronic renal disease. Nineteen patients had primary renal disease, and 15 patients had diabetic nephropathy. Except for antihypertensive therapy no specific treatment to modify the progression of the disease was given during the follow-up. The rate of progression was determined by repeated measurements of the glomerular filtration rate (GFR). The time of follow-up ranged from 12 to 91 months with an average of 39.7 +/- 16.7 months. The mean initial GFR was 34.7 +/- 13.9 ml/min x 1.73 m2 body surface area and the average decline in renal function was -0.27 +/- 0.26 ml/min/month. The entry levels of triglycerides (TG; p = 0.04), very-low-density lipoprotein cholesterol (p = 0.03), apolipoprotein-B (ApoB; p = 0.008) and systolic blood pressure (SBP; p = 0.04) were significantly correlated with the rate of progression. Among lipoprotein variables, ApoB showed the strongest correlation with the decline in GFR. Patients with a progressive course of their disease also tended to have initially higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (NS), whereas the initial plasma concentration of high-density lipoprotein cholesterol did not show an association with the progression of renal insufficiency.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446265 TI - Mucosal immunity in primary glomerulonephritis. III. Study of intestinal permeability. AB - To study the specificity of gut hyperpermeability in primary glomerulonephritis, we investigated intestinal permeability by means of 51Cr-EDTA testing in 20 healthy individuals and in 30 patients with Immunoglobulin A nephropathy (IgA GN), 25 with idiopathic nephrotic syndrome (INS) and 20 with immune complex glomerulonephritis (IC-GN; membranous+membranoproliferative glomerulonephritis). Gut permeability was statistically increased in each patient group versus the controls [controls: 2% (0.4-3.9); IgA GN: 3.25% (0.7-17.70); INS: 3.71% (0.82 10); IC-GN: 3.40% (0.30-16); results are median (range); p < 0.005, nonparametric Mann-Whitney test]. An increase in intestinal permeability exceeding the upper limit of control values (95th percentile) was observed in 36% of IgA GN, 60% of INS and 50% of IC-GN patients. We conclude that intestinal permeability is frequently increased in primary glomerulonephritis and may also be increased in types of glomerulonephritis other than IgA GN. PMID- 8446266 TI - Influence of cardiovascular damage and residual renal function on plasma endothelin in chronic renal failure. AB - To study the influence of cardiovascular damage on plasma endothelin in chronic renal failure, we have measured the plasma concentration of this peptide in 32 uremic patients (7 undialyzed uremics, 8 CAPD patients and 16 hemodialysis patients) and in 9 healthy subjects. Sixteen patients had severe cardiovascular damage while the other 16 had no cardiovascular involvement. Endothelin was markedly raised (p < 0.01) in the uremic group as a whole (13.9 +/- 2.6 pmol/l) in comparison with the group of healthy subjects (8.6 +/- 1.6 pmol/l). Hemodialysis patients displayed endothelin levels much higher (p < 0.01) than CAPD patients and undialyzed uremics. Endothelin was directely related with BUN (r = 0.37) and with serum creatinine (r = 0.52) in dialysis patients. Similar correlations were also found in undialyzed uremics. Plasma endothelin was almost identical in patients with severe cardiovascular damage (15.5 +/- 1.6 pmol/l) and in those without cardiovascular involvement (15.9 +/- 2.6 pmol/l). There was no relationship between arterial pressure and plasma endothelin. Residual renal function is an important determinant of circulating endothelin even at very advanced stages of renal insufficiency. It appears unlikely that atherosclerosis plays a major role in the pathogenesis of high plasma concentration of this peptide in uremic patients. PMID- 8446267 TI - Natriuretic and vasoactive hormones and glomerular hyperfiltration in hyperglycaemic type 2 diabetic patients: effect of insulin treatment. AB - Evidence that an increase in plasma atrial natriuretic peptide (ANP) concentrations mediates, at least in part, glomerular hyperfiltration in diabetic rats prompted us to study the relationship between ANP and renal haemodynamics in hyperfiltering type 2 diabetic patients in association with other hormones implicated in the control of glomerular filtration rate (GFR) (catecholamines, vasopressin, renin) and in sodium tubular transport (aldosterone, ouabain displacing factor, ODF). Since hyperglycaemia is also associated to hyperfiltration, diabetic patients who presented with secondary drug failure were studied both in hyperglycaemic and in normoglycaemic condition. For this purpose, 11 normotensive non-macroproteinuric hyperfiltering patients with type 2 diabetes were treated with an 8-day continuous insulin infusion (days 0-7). Dehydration was prevented or corrected and natriuresis was on day 0 above 100 mmol/day. The following parameters were determined on days 0 and 7: GFR and renal plasma flow (RPF) by 99mTc-DTPA and 131I-hippuran clearances; the extracellular volume, assimilated to the DTPA diffusion volume; urinary ODF by receptor-binding assay and urinary as well as plasma catecholamines by HPLC after extraction on alumin. Plasma ANP and antidiuretic hormone (ADH) were measured by radioimmunoassay after extraction on phenyl-silylsilica (ANP) and with ether (ADH). Unextracted plasma was used for radioimmunological measurement of plasma renin activity and aldosterone. When correcting hyperglycaemia to normoglycaemia GFR decreased from high to normal mean value (138 +/- 27 and 115 +/- 6 ml/min, p < 0.001), RPF followed the same trend, and the DTPA diffusion volume did not change.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446268 TI - Changes in plasma levels of vasoactive peptides during standard bicarbonate hemodialysis. AB - During bicarbonate hemodialysis, there is an increase in peripheral vascular resistance of nonadrenergic origin, counteracting the hypotensive effect of fluid removal during the course of the dialysis. In this study, the plasma levels of vasoactive regulatory peptides, noradrenaline and renin, were investigated in 11 patients with chronic renal failure during standard bicarbonate hemodialysis (STHD) for 270 min. As regards vasoconstrictors, an increase in gamma 2 melanocyte-stimulating hormone (gamma 2-MSH), neuropeptide Y (NPY) and plasma renin activity (PRA) occurred. However, arginine vasopressin and noradrenaline were unchanged. With respect to vasodilators, calcitonin gene-related peptide was not changed. An initial increase in beta-endorphin (beta-END) occurred, followed by a decrease during the remaining part of the treatment. Motilin decreased during the first part of the treatment but increased to the baseline level during the latter part. An increase in substance P was observed while vasoactive intestinal peptide decreased. We conclude that an increase in vasoconstricting substances (gamma 2-MSH, NPY, PRA) occurs during STHD, probably owing to the decrease in plasma volume. With the exception of beta-END, the changes in vasodilators were fairly small. The data suggest that vasoactive substances might participate in the hemodynamic response to hemodialysis. PMID- 8446269 TI - Changes in plasma levels of vasoactive peptides during sequential bicarbonate hemodialysis. AB - The hemodynamic response to isolated ultrafiltration (IUF) is characterized by a vasoconstriction, while there is no significant change in peripheral vascular resistance during isovolemic bicarbonate hemodialysis (IVHD). The present investigation was designed to study the plasma levels of vasoactive regulatory peptides together with noradrenaline (NA) and plasma renin activity (PRA) in 11 patients during sequential hemodialysis (SQHD) - IUF for 60 min, followed by IVHD for 210 min. During IUF, the vasoconstrictors arginine vasopressin (AVP), gamma 2 melanocyte-stimulating hormone (gamma 2-MSH), neuropeptide Y (NPY), NA and PRA increased. During IVHD, NPY and PRA remained unchanged on a higher level. A decrease in AVP below the baseline and in gamma 2-MSH and NA to the baseline levels occurred during IVHD. In the case of vasodilators, there were no changes in calcitonin gene-related peptide or motilin during SQHD. An increase in beta endorphin (beta-END) occurred during IUF, followed by a decrease during IVHD. Substance P and vasoactive intestinal peptide were unchanged during IUF but decreased during IVHD. We conclude that SQHD is characterized by an increase in all the measured vasoconstrictors during IUF in response to loss of fluid, and by a decrease in some vasoconstrictors (AVP, gamma 2-MSH, NA) during IVHD. With the exception of beta-END, there were no changes or only minor ones in vasodilators during SQHD. There are changes in plasma levels of vasoactive substances during SQHD but the importance of these changes for the hemodynamic adaptation to ultrafiltration and dialysis needs to be studied further. PMID- 8446270 TI - Characteristic glomerular lesions in the ExHC rat: a unique model for lipid induced glomerular injury. AB - ExHC rats were bred from the Sprague-Dawley strain and are highly susceptible to dietary hypercholesterolemic stimuli. Although chemical and histological examination of the aorta from ExHC rats fed a diet containing 3% cholesterol, 0.6% sodium cholate and 15% olive oil (high-cholesterol diet, HCD) has been reported, renal injury in this model has not been investigated to date. Therefore, we examined the renal pathological changes and proteinuria in this model. ExHC rats fed an HCD developed proteinuria and characteristic glomerular lesions within 4-8 weeks after initiation of the diet. The most striking glomerular change observed in this model was the marked accumulation of numerous lipid-filled foam cells, with a surface marker that identified them as macrophages, within the mesangial regions which could have been involved in focal and segmental glomerular sclerosis. Our study demonstrates that ExHC rats fed a cholesterol-supplemented diet develop glomerular injury that may be mediated by infiltrating macrophages. These results imply that ExHC rats may be well-suited for the use in investigations of the role of macrophages in the pathogenesis of lipid-induced glomerular injury. PMID- 8446271 TI - Effects of antihypertensive drugs on the progress of renal failure in hyperlipidemic Imai rats. AB - Hyperlipidemic Imai rats spontaneously develop hypercholesterolemia, proteinuria and glomerulosclerosis. The aim of the present study was to clarify whether two different antihypertensive regimens (enalapril and a combination of reserpine, hydralazine and hydrochlorothiazide) would offer similar degrees of protection against glomerular injury in male hyperlipidemic Imai rats. Group 1 (n = 4) received no specific therapy. Group 2 (n = 4) was treated with enalapril at a dose of 50 mg/l in drinking water starting at 6 weeks of age. Group 3 (n = 5) was treated with the triple drug regimen (reserpine 5 mg/l, hydralazine 80 mg/l and hydrochlorothiazide 25 mg/l in drinking water). Body weight, blood pressure, urinary protein, serum albumin, cholesterol, BUN and serum creatinine were checked and compared among groups. Although enalapril and triple drug therapy were almost equally effective in controlling systemic hypertension, there were striking differences between the two treated groups in proteinuria, hypercholesterolemia and glomerular injury. Enalapril treatment significantly reduced proteinuria (731 +/- 23 vs. 256 +/- 144 mg/kg/day at 36 week; p < 0.005) and hypercholesterolemia (264 +/- 17 vs. 104 +/- 17 mg/dl at 38 weeks; p < 0.001). Triple drug therapy failed to prevent the development of proteinuria (909 +/- 75 mg/kg/day at 38 weeks) and hypercholesterolemia (330 +/- 61 mg/dl at 38 weeks). The glomerulosclerosis index was significantly higher in untreated control rats (229 +/- 65) and in triple drug-treated rats (218 +/- 59) than in the enalapril-treated group (24 +/- 12; p < 0.05, and p < 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446272 TI - Skeletal muscle metabolism in uremic rats: a 31P-magnetic resonance study. AB - The effect of uremia on skeletal muscle metabolism of the rat was examined using 31P-magnetic resonance spectroscopy. Three weeks following either a 5/6 nephrectomy or a sham operation, Wistar rats were placed in a 7T magnet, and the sciatic nerve was stimulated for 10 min. Analysis of spectra allowed calculation of intracellular pH and the relative concentrations of phosphocreatine (PCr), inorganic phosphate (Pi) and ATP. [ADP] was calculated from the creatine kinase equilibrium. There was a significant reduction in the resting intracellular [Pi] despite an elevation in extracellular [Pi], probably due to a reduction in the activity of the membrane Na/Pi cotransporter on account of a reduced sodium gradient. Despite anemia and uremia, there were no significant metabolic abnormalities during exercise and recovery accompanying this substantial reduction in glomerular filtration rate implying that at this level of renal impairment, there is no mitochondrial dysfunction. PMID- 8446273 TI - Long-term cyclosporin A therapy for severe idiopathic membranous nephropathy. AB - Fifteen patients with nephrotic idiopathic membranous nephropathy (MN) with predictors of poor outcome were treated with a long cyclosporin A (CyA) regimen at the dose of 4-5 mg/kg/day for a median period of 15 months (range 12-30). Four of the 15 patients did not respond to CyA, and the therapy was discontinued after 4 months. A partial remission (proteinuria < 2 g/day) was observed in 7 of 15 patients and a complete remission (proteinuria < 0.2 g/day) in 4 of 15 patients; good results (partial+complete remission) were, thus, obtained in 11 of 15 patients (73%). Two patients are still receiving therapy. A relapse of the nephrotic syndrome occurred in 3 of 9 patients on withdrawal of CyA, but the relapse remained sensitive to CyA. Side effects were mild. We conclude that CyA may be efficient in the treatment of MN and should be evaluated in controlled trials. PMID- 8446274 TI - Renal potassium wasting in the absence of aldosterone. Insights into the mechanism for the secretion of potassium. AB - This report focuses on the possible pathophysiology of a renal lesion that led to hypokalemia and the excessive excretion of potassium (K+) in a 2.5-year-old child. The rate of excretion of K+ was high, largely the result of forces leading to a very high concentration of K+ in the lumen of the terminal cortical collecting duct as revealed by very high values for the transtubular K+ concentration gradient (TTKG was 25 +/- 3). The TTKG was high despite undetectable levels of aldosterone in plasma and the absence of bicarbonaturia. The level of renin in plasma was not low and there was a tendency to contraction of the ECF volume when dietary intake was curtailed. These findings provided the basis to speculate that the underlying lesion might be a lower than normal 'permeability' of the cortical collecting duct for chloride. PMID- 8446275 TI - Membranous nephropathy associated with nodular sclerosing Hodgkin's disease. AB - A 61-year-old man developed steroid-resistant nephrotic syndrome in which renal biopsy showed membranous nephropathy. Six months after the initial presentation, nodular sclerosing Hodgkin's disease was diagnosed. Cyclophosphamide, vincristine, prednisolone and procariazine chemotherapy was administered, after which proteinuria gradually decreased resulting in complete remission in the course of 7 months. A second renal biopsy, which was undertaken 4 months after complete remission, revealed significant histological improvement with disappearance of immune deposit. PMID- 8446276 TI - Unilateral breast enlargement secondary to hemodialysis arteriovenous fistula and subclavian vein occlusion. AB - Placement of permanent arteriovenous accesses or of temporary subclavian dual lumen catheters for hemodialysis can be associated with significant edema of the ipsilateral arm due to venous occlusion. We report an unusual case of marked breast enlargement secondary to hemodialysis arteriovenous fistula, and subclavian vein occlusion proximal to the junction of the mammary vein. To our knowledge, this is a rare complication of hemodialysis accesses. Breast enlargement associated with hemodialysis arteriovenous fistulae, especially in the presence of a history of subclavian vein catheterization, may be indicative of ipsilateral subclavian vein stenosis/thrombosis. PMID- 8446277 TI - Mediastinal hematoma: a rare complication of subclavian catheterization for hemodialysis. PMID- 8446278 TI - Elevation of serum IgA1 levels in patients with diabetic nephropathy. PMID- 8446279 TI - Leukocytoclastic vasculitis in association with cryoglobulinemia and renal cell carcinoma. PMID- 8446280 TI - Triple Wegener's granulomatosis in the urogenital tract. PMID- 8446281 TI - Optic neuritis following treatment with isoniazid in a hemodialyzed patient. PMID- 8446282 TI - Intraperitoneal infusion of dialysate: a possible cause of increased plasma atrial natriuretic peptide levels. PMID- 8446283 TI - Short- and long-term effects of felodipine on circulating endothelin and atrial natriuretic peptide levels in essential hypertension. PMID- 8446284 TI - Retinal lesions specific for membranoproliferative glomerulonephritis type II: description of 2 cases. PMID- 8446285 TI - Comparative evaluation of beta 2-microglobulin removal by different hemodialysis membranes: a six-year follow-up. PMID- 8446286 TI - Changes in nephritic factor in hypocomplementemia. PMID- 8446287 TI - Tolosa-Hunt syndrome complicated with chronic hemodialysis. PMID- 8446288 TI - [Ventral perforations in lumbar intervertebral disk operations--a catamnestic study]. AB - Iatrogenic injuries of prevertebral structures during lumbar disc surgery area a rare albeit important complication, since they may be life-threatening. A short survey is given concerning the frequency and kind of prevertebral injuries as they are presented in the literature. Own experiences and a case of an AV-fistula following disc surgery are described. Finally, legal aspects of German law concerning the physician's duty to inform the patient of operative risks are discussed. PMID- 8446289 TI - [Bicycle rider's ulnar nerve paralysis]. AB - The ulnar neuropathy in bicycle riders is a less common occurrence, due to a local damage of the nerve on the level of the ulnar tunnel. It has been described in neurological literature only a few times, and hence its good prognosis is not sufficiently known. Within a short time two patients of this disease were transferred to our clinic for operation. After a local space-occupying growth in the tunnel could be excluded by MR or sonography of the wrist, we discouraged performance of an operative procedure. The patients' complaints and the neurological deficits vanished in a few weeks. Ulnar neuropathy in bicycle riders is therefore a syndrome for which even in the case of severe deficit an operation is not recommended. PMID- 8446290 TI - [Neuralgia of the glossopharyngeal nerve with syncope attacks]. AB - The anatomical viewpoints of nervus IX and its surrounding structures are explained. The authors report on one case of symptomatology of glossopharyngeal neuralgia combined with cardiac arrests. Finally, pathogenesis and surgical treatment of glossopharyngeal neuralgia are discussed. PMID- 8446291 TI - Spontaneous shrinking of a macroprolactinoma. AB - The case of a male patient with a macroprolactinoma is presented. Within a follow up period of six months the tumor had spontaneously shrunken without any therapy. The causes of this phenomenon are discussed in the following paper. PMID- 8446292 TI - Magnetic resonance imaging in the diagnosis of idiopathic giant-cell granulomatous hypophysitis: a rare cause of hyperprolactinaemia. AB - Idiopathic giant cell granulomatous hypophysitis is a rare disorder of pituitary gland characterised by a chronic inflammatory process. It can also be an extremely rare cause of hyperprolactinaemia. In this paper, we present our experience with two cases of idiopathic giant cell granulomatous hypophysitis manifested by hyperprolactinaemia, and their neuroradiological evaluation including preoperative MRI studies in one of them, and discuss our findings in the light of the literature. PMID- 8446293 TI - A squamous cell carcinoma originated from intracranial dermoid cyst. AB - A 59-year-old female had been treated for epilepsy over 20 years. She had frequent convulsive seizures in spite of medication and was admitted to our hospital in status epilepticus. CT showed low density cyst with calcified wall at right suprasellar region and irregular ring enhancement in the frontal lobe which was continuous with the cyst. Angiography revealed tumor stain in the venous phase. The frontal mass was removed with evacuation of the cyst. Pathological findings were suggestive of squamous cell carcinoma arising from the epithelial component of the pre-existing dermoid cyst. The patient died six months after the operation with severe hyperglycemia, ketoacidosis and hypotension probably due to chemical meningitis and hydrocephalus. PMID- 8446294 TI - Ipsilateral motor symptoms caused by a right pterional meningioma. AB - The case is reported of a patient bearing a pterional meningioma on the right (non-dominant) side manifesting with ipsilateral motor symptoms, completely recovered after tumor removal. The occurrence of ipsilateral sensory and/or motor symptoms, probably due to direct or indirect involvement of the sensory/motor secondary areas of the insula of Reil, may be misleading in diagnosis because of apparent incongruity between clinical presentation and radiological findings. Only seven cases of such a condition, all localized on the left (dominant) side, have been previously reported. PMID- 8446295 TI - [Malignant lymphomas with first manifestation in the spine as a rare differential diagnosis of lumbar intervertebral disk syndrome]. AB - Spinal epidural lymphoma need rarely be considered as a cause of lumbar nerve root compression. We report on two patients suffering from malignant epidural non Hodgkin lymphoma, admitted with clinical and radiological signs of a lumbar herniated disc. Non-Hodgkin lymphoma can affect the spinal cord and nerve roots rarely as an isolated epidural spinal infiltration in the absence of widespread disease or - as in our two cases - as the first feature of disseminated systemic disease. Epidural non-Hodgkin lymphoma with neurological deficits should be treated by early decompressive (hemi-)laminectomy, postoperative radiotherapy and chemotherapy. PMID- 8446296 TI - Why Clinton's health plan is doomed. PMID- 8446297 TI - Variable cutaneous manifestations of Lyme disease. AB - Lyme disease is a complex, multisystem illness that primarily affects the skin, nervous system, heart, and joints. Physicians must learn to recognize the various possible presentations of the pathognomonic skin lesion to diagnosis this disease in the absence of reliable laboratory methods. PMID- 8446298 TI - Laparoscopic hysterectomy, appendectomy, and cholecystectomy. AB - This paper presents the first recorded combined laparoscopic hysterectomy, appendectomy, and cholecystectomy. The performance of these procedures, in experienced hands, did not alter the outcome. Underlying pathology included uterine myomas, pelvic adhesive disease, and symptomatic gallstones. PMID- 8446299 TI - Advance directives for the elderly: a survey. AB - In 1991, the New Jersey Legislature passed the New Jersey Advance Directives for Health Care Act. We surveyed the elderly about their knowledge and interest in advance directives, their preferences regarding end-of-life care, and whether their physicians discuss these matters. PMID- 8446300 TI - Correlation of therapeutic modalities and mortality in critical care. AB - Severity scoring systems are time consuming for physicians and other health professionals. In addition, they are unlikely to be used by resident physicians wishing to have a quantitative measure of a patient's severity. The authors describe a new critical care scoring system. PMID- 8446301 TI - Humoral mediation of changing body composition during aging and chronic inflammation. AB - A decline in lean body mass and an accompanying increase in fat mass are known to occur during aging. The consequences of these changes in body composition may include decreased strength and physical activity, altered energy metabolism, and impaired resistance to infection. The mechanisms behind these age-related events remain unknown, but they may include changes in some of the hormonal and cytokine mediators that seem to regulate body composition. The common inflammatory condition rheumatoid arthritis could provide a useful model of these phenomena dissociated from chronological aging. This article reviews changes in neuroendocrine and immune modulators of metabolism and their consequences during aging and chronic inflammation. PMID- 8446302 TI - Pathogenesis of cobalamin neuropathy: deficiency of nervous system S adenosylmethionine? AB - Low levels of cerebrospinal S-adenosylmethionine in association with abnormal myelination in inherited disorders affecting cobalamin and folate metabolism provide new data on a possible mechanism of cobalamin neuropathy. PMID- 8446303 TI - Long-term compliance with a lipid-lowering diet. AB - Compliance with a lipid-lowering diet was sustained in only 30% of patients following an initial three-month intervention. Additional strategies are required to support long-term adherence. PMID- 8446304 TI - Free fatty acids in plasma may exert feed-back control of lipoprotein lipase activity. AB - Free fatty acids released through hydrolysis of triacylglycerols by lipoprotein lipase at the vascular epithelium may act in feedback control of lipoprotein lipase activity. PMID- 8446305 TI - Are older Americans making better food choices to meet diet and health recommendations? AB - Trends in food consumption by elderly men and women were recently reported using data from the US Nationwide Food Consumption Surveys of 1977-1978 and 1987-1988. Problems of interpretation arise because of the significant nonresponse rates that occurred during the NFCS survey and other difficulties related to comparison of population nutrient intakes over time. PMID- 8446306 TI - Age-associated loss of carrier-mediated intestinal taurine transport in cats. AB - Taurine uptake across the intestinal brush border membrane of the adult cat seems not to be mediated by a specific transport mechanism. Therefore taurine absorption from the gastrointestinal tract will possibly become a limiting factor for maintenance of taurine homeostasis in the cat under conditions of decreased dietary taurine intake. PMID- 8446307 TI - Fish oil and immune function. PMID- 8446308 TI - Exercise and lean weight. PMID- 8446309 TI - A tale of two Justins. PMID- 8446310 TI - A prayer for Lillian. PMID- 8446311 TI - AIDS update. PMID- 8446312 TI - Myths & facts ... about charting. PMID- 8446313 TI - Abdominal hemorrhage. PMID- 8446314 TI - Using blood glucose meters. What you and your patient need to know. Part I. PMID- 8446315 TI - Pearl's greatest strength. PMID- 8446316 TI - Sheila's death created many rings of life. PMID- 8446317 TI - Close-up on scaphoid fracture. PMID- 8446318 TI - To tell or not to tell. PMID- 8446319 TI - Managing the crisis of AVM. PMID- 8446320 TI - Alternating transparent & hydrocolloid dressings--a difficult case. PMID- 8446321 TI - Heroes of Hurricane Andrew. PMID- 8446322 TI - IV ketorolac: getting to the route of a problem. PMID- 8446323 TI - The quilting club. PMID- 8446324 TI - Nurse's guide to O.T.C. analgesics. PMID- 8446325 TI - Positive self-talk. PMID- 8446326 TI - Nasal secretions in ocular surgery under general and local anesthesia. AB - To investigate the etiology of nasopharyngeal secretion reflux under anesthesia, which could contaminate the conjunctiva, we photographed, after preoperative nasal instillation of fluorescein, the faces of 224 consecutive patients having cataract surgery under general (n = 78) and local (n = 146) anesthesia. In 10 patients, extension of the neck and facial contour caused fluid to drain from the nose directly into the conjunctival cul-de-sac. Nine of the 78 patients under general anesthesia had nasal secretions on the face at the end of surgery, usually due to leaking around the endotracheal tube. Adjusting head posture by moderate neck flexion and taking care to prevent leakage around the endotracheal tube, together with antiseptic preparation of the nose, may prevent contamination of the operative field by nasal secretions. PMID- 8446327 TI - Refractive hazards of intraoperative retinal photocoagulation. AB - The refractions of a laser beam during transpupillary and endo-ocular intraoperative retinal photocoagulation as it passes through vitreous substitutes, with varying refractive indexes, were investigated with the use of mathematical algorithms and ray tracers. The following modifications and potential hazards were noted: 1) deviations of the laser beam (unlikely, however, to cause target error when surgery is properly conducted); 2) variations in laser beam diameter and power density (up to 60%), easily leading to retinal underexposure or overexposure; and 3) asymmetry in beam distribution at the target site, leading to non-uniform retinal photocoagulation. Proper surgical techniques must be adopted before and during intraoperative photocoagulation to minimize retinal hazards. The relatively short distance between the endolaser probe and the retina means that fewer undesirable refractions occur with endo ocular photocoagulation than with transpupillary indirect intraoperative photocoagulation. PMID- 8446328 TI - Anterior chamber reaction after mitomycin and 5-fluorouracil trabeculectomy: a comparative study. AB - We measured aqueous flare in 16 glaucomatous eyes after trabeculectomy in which 5 fluorouracil (5-FU) or mitomycin C (MMC) had been used as an adjunctive therapy. The eyes were divided into a 5-FU and an MMC group, matched for factors that might influence the postoperative inflammatory response to intraocular surgery. Seven eyes of seven patients received subconjunctival injections of 5-FU (50 mg in 2 weeks) and nine eyes of nine patients were given 0.2 mg/0.5 mL MMC intraoperatively. The aqueous flare converted to an albumin concentration (mg/dL) was significantly higher in the 5-FU group than in the MMC group (359.6 +/- 113.8 mg/dL and 143.2 +/- 46.7 mg/dL, respectively; Mann-Whitney U test, P < .05) on the second postoperative day. Intraoperative MMC appears to be no more harmful to the blood-aqueous barrier than 5-FU. PMID- 8446329 TI - Measured and predicted anterior chamber depth for transscleral suture-fixated posterior chamber intraocular lenses. AB - Variables in intraocular lens (IOL) power calculations include axial length, average dioptric power of the cornea, and an assumed pseudophakic anterior chamber depth (ACD). In the case of transscleral suture-fixated posterior chamber (PC) IOLs, ACD depends on the placement of the suture and thus might be expected to vary more than it does in eyes with capsular-fixated IOLs. To assess the degree of this variation, we determined the postoperative pseudophakic ACD using A-scan ultrasonography in 15 patients with transscleral suture-fixated PC-IOLs. The mean pseudophakic ACD (posterior corneal vertex to anterior pseudophakos) was 3.47 +/- 0.69 mm. The mean absolute discrepancies in ACD between these measured values and those predicted by the original Binkhorst and the most recent Holladay formulas were 0.579 +/- 0.513 mm and 0.639 +/- 0.519 mm, respectively. In 11 of 15 eyes, the measured ACD was within 1 mm of that predicted by either the Binkhorst or Holladay formula, suggesting that either will provide reasonable estimates of ACD for IOL power calculations for suture-fixated PC-IOLs. PMID- 8446330 TI - Peters' anomaly: a review of 26 penetrating keratoplasties in infants. AB - We reviewed the specimen records log of the McGee Eye Institute Histopathology Service from January 1979 to December 1990 for penetrating keratoplasty specimens submitted with a clinical diagnosis of Peters' anomaly. The records of the 19 cases thereby identified were reviewed for clinical outcome and visual rehabilitation, and the histopathology of all specimens was reviewed and correlated with the clinical diagnosis. Two specimens from the same patient were eliminated as histopathologically inconsistent with Peters' anomaly; one patient's data were not used because the patient was an adult when first grafted. Six eyes were grafted two or more times, for a total of 26 grafts on 16 eyes in 10 patients. Mean age at the time of first transplant was 18 weeks (range, 3 weeks to 40 months). Mean follow up was 30 months (range, 7 months to 6 1/2 years). Five eyes had preoperative glaucoma which persisted postoperatively. Ten eyes developed glaucoma postoperatively. Of the 15 eyes with glaucoma, 14 were uncontrolled medically and 12 underwent cyclodestructive or Molteno filtering procedures, or both, to control pressure. Graft rejection developed in 9 of the 10 eyes that required a cyclodestructive procedure, with partial or complete graft failure occurring shortly after the procedure. Glaucoma did not develop in one eye; in one other eye, it was medically controlled. These 2 eyes maintained clear grafts. Of the 6 eyes that were regrafted, only 1 obtained ambulatory vision. Of the 26 eyes receiving grafts, the grafts failed completely in 17 and partially in 5; 4 have remained clear. Five patients maintain ambulatory vision. PMID- 8446331 TI - Of honesty and electroretinographic responses to ischemia in pancreatectomized rats. PMID- 8446332 TI - Allograft rejection after penetrating keratoplasty for keratoconus. AB - We retrospectively studied 91 penetrating keratoplasties in 65 patients to evaluate the overall incidence of allograft rejection and the incidence in unilateral as compared with bilateral cases following penetrating keratoplasty for keratoconus. All surgeries were performed by the senior author following a standardized technique. The average age of the patients was 35 years; the average follow up, 6.5 years. Nine of the 91 grafts (9.9%) were rejected. The time of rejection varied from 6 months to 13 years after surgery. Eight of the nine rejections (88.9%) were reversible with steroid treatment and have survived up to 10 years. One graft failure requiring repeat penetrating keratoplasty (1.1%) occurred 13.25 years after surgery. The unrejected clear grafts have survived up to 21.5 years. The results of this study support the excellent prognosis of penetrating keratoplasty for keratoconus. PMID- 8446333 TI - Sympathetic ophthalmia after cyclocryotherapy of neovascular glaucoma without ocular penetration. AB - A 66-year-old man underwent cyclocryotherapy for treatment of neovascular glaucoma in a blind eye. Although neither history, clinical examination, nor histologic evaluation uncovered any ocular penetration, he subsequently developed sympathetic ophthalmia. This and other cases suggest that cyclocryotherapy could be a factor in the pathogenesis of sympathetic ophthalmia, although the mechanism is far from clear. PMID- 8446334 TI - Collagen plug occlusion of Molteno tube shunts. AB - We report five patients in whom collagen lacrimal plugs were used to temporarily occlude the lumen of Molteno shunts to prevent early postoperative hypotony. Only one eye, with a double plate, developed hypotony and a flat anterior chamber that required reformation. However, in three patients, the collagen plugs did not dissolve and had to be removed surgically to lower the intraocular pressure. Although the semipermeability of collagen is desirable, its unpredictable degradation renders it unsuitable for temporary occlusion of tube shunts. Other biodegradable materials may be more appropriate for this purpose. PMID- 8446335 TI - Visual recovery following transethmoidal optic nerve decompression in traumatic optic neuropathy. PMID- 8446336 TI - Treatment of dry eye by moving the lacrimal punctum to dry dock. AB - Several methods for occluding the lacrimal canaliculi to prevent spontaneous drainage have been described for the treatment of dry eye. These techniques have been either of short duration or irreversible. We have developed a technique in which the vertical portion of the lacrimal canaliculus is transferred anteriorly, and the lacrimal punctum is placed between the eyelashes, where it is out of the lacrimal meniscus and therefore nonfunctional. If the quantity of lacrimal secretion improves, the vertical portion of the lacrimal canaliculus may be returned to its original site, allowing normal lacrimal flow. The technique was successful in 12 puncta of seven patients with more than 5 years of follow up. The operation was easily reversed in the two puncta of one patient who complained of epiphora after lacrimal secretion had improved, allowing spontaneous tear drainage. PMID- 8446337 TI - A new method for posterior sub-Tenon's drug administration. AB - We describe a technique of sub-Tenon's drug administration involving the use of a strip of collagen sponge connected with a silicone tube. The strip is implanted in the sub-Tenon's space and the free end of the tube is attached to the patient's forehead. Medication is infused through the tube two to four times a day for 7 to 10 days; then the tube is removed. We have used this technique, without serious complications, in the treatment of 230 patients with various diseases of the posterior segment and the anterior part of the optic nerve. PMID- 8446339 TI - Storage of sulfur hexafluoride gas. PMID- 8446338 TI - Laser sclerostomy ab externo using mid infrared lasers. AB - An ab externo fistulizing procedure (sclerostomy) was performed in vivo in 48 rabbit eyes using a pulsed (20 microseconds and 200 microseconds) Holmium:YAG (Ho:YAG) laser (2120 nm) and a pulsed (200 microseconds) Erbium:YAG (Er:YAG) laser (2940 nm). The laser energy was delivered via an infrared transmitting fiber in contact with the sclera, with the fiber inserted into a specially sharpened retractable cannula in order to guide it into the subconjunctival space. An additional optical fiber-fiber coupling system was required for the Er YAG laser. A patent fistula (200-micrometers diameter) with formation of a filtering bleb and marked intraocular pressure reduction was achieved in nearly all cases. Significant intraoperative or postoperative complications occurred only with the 20-microsecond Ho:YAG laser. Trauma to the conjunctiva was as minimal as in a subconjunctival injection. The Er:YAG laser created a smaller thermal damage zone at the fistula walls and required significantly less laser energy than the Ho-YAG laser. PMID- 8446340 TI - Monitored local anesthesia for pars plana vitrectomy. PMID- 8446341 TI - Temperature distributions in porcine orbital tissues following the use of CO2 and Nd:YAG lasers. AB - Temperature distributions in the orbital tissues of a live porcine model were obtained during and immediately following the application of CO2 and Nd:YAG (both contact and noncontact) laser irradiation to muscle tissue adjacent to the optic nerve. Temperatures were measured with thermocouples and an infrared-sensitive thermographic camera system. Significant thermal spread was observed only in the case of the contact Nd:YAG laser, along with histologic evidence of damage to the optic nerve. After the laser was switched off, the target cooled with a time constant on the order of 10 seconds. PMID- 8446342 TI - Mersilene mesh and fascia lata in brow suspension: a comparative study. AB - I retrospectively compared 34 brow suspension procedures: 17 using Mersilene mesh and 17 using stored, irradiated fascia lata. Good results were obtained with both materials. Since Mersilene mesh is inexpensive, easy to prepare and work with, and can be sterilized and guaranteed free of infectious diseases, it is an acceptable alternative if fascia lata is unavailable. PMID- 8446343 TI - Granny knot for interrupted 10-0 nylon sutures in cataract sections. AB - A granny knot instead of a reef (square) knot is advocated for 10-0 nylon interrupted sutures in limbal cataract sections, especially under a conjunctival flap. The second of the two throws is looped in the direction opposite to that in a reef knot so that the free ends lie at right angles to the plane of the suture. The second throw is used to "run down" the first to tighten the suture. To avoid postoperative erosion through conjunctiva, the ends are cut long with a blade while they lie flush with the sclera. The knot is locked when the traction required to tighten the suture is released and the thinned nylon recovers its original diameter on each side of the knot. PMID- 8446344 TI - A transcorneal modification for scleral fixation of posterior chamber intraocular lenses. AB - A simple transcorneal surgical modification for scleral fixation of posterior chamber intraocular lenses is described for use in cases in which posterior capsule or zonular support are missing or unsafe. The technique allows a "closed" eye system to be maintained with minimal intraocular manipulation. PMID- 8446345 TI - Bacterial endophthalmitis following cataract surgery in an eye with a preexisting Molteno implant. AB - We describe a patient with a preexisting, functioning Molteno implant in whom acute endophthalmitis developed following cataract extraction. The condition was treated successfully without removing the implant. PMID- 8446346 TI - Nd:YLF laser sclerostomy. AB - We used a Q-switched Nd:YLF picosecond laser, operating at the 1053-nanometer wavelength with a spot separation of 10 microns and a crossing width of 1000 x 10 microns in a rectangular pattern, to create ab externo sclerostomies in 12 New Zealand white rabbits. The mean energy used was 30 J (range, 24 to 65 J). Filtering blebs were observed for 1 week, with a concurrent drop in intraocular pressure. Histology performed at days 3, 10, and 30 revealed clean-cut sclerostomies, with minimal thermal and mechanical damage. PMID- 8446347 TI - Curved, sub-tenon cannula for local anesthesia. AB - I describe a new cannula for delivery of sub-Tenon's local anesthetic solution. The cannula has a rigid structure, a 19-gauge diameter, and a shaft with a gentle curve, specifically designed to follow the contour of the globe. Anteroposterior flattening of the tip facilitates advancement of the cannula within the potential Tenon's-space tissue plane. Without the acute angulation of the shaft of the Bishop-Harmon-style cannula, it is easier to follow the globe contour and create less tenting-up of conjunctiva. PMID- 8446348 TI - Mitomycin as adjunct therapy in correcting iatrogenic punctal stenosis. AB - A 52-year-old woman developed persistent epiphora in her left eye after undergoing occlusion of the left puncta. Two attempts to reopen the puncta with a one-snip procedure and placement of punctal silicone plugs failed. The epiphora resolved and the puncta remained patent after the patient underwent a third one snip procedure, supplemented with topical mitomycin during and after surgery. PMID- 8446349 TI - Microwave-induced retinal destruction with sparing of sclera and choriocapillaris. AB - We studied the effect of short-term hyperthermia on sclera, choroid, and retina by delivering microwave radiation (2.45 GHz) for 1 minute to 12 eyes of Dutch belted pigmented rabbits. Four eyes each were treated with 43 degrees C, 45 degrees C, and 47 degrees C and followed for 4 weeks. The 43 degrees C group showed minimal disruption of retinal pigment epithelium and outer retina, with pigment migration; the 45 degrees C and 47 degrees C groups showed complete retinal and RPE damage, pigment migration, and glial proliferation. At the same time, the sclera and choroid in all of the eyes remained essentially unchanged. We conclude that microwave-induced hyperthermia can create retinal scarring without significant damage to sclera and choriocapillaris. The next experimental step will be to refine the microwave delivery system to ensure predictable and reproducible lesions. PMID- 8446350 TI - Plateau iris syndrome: ultrasound biomicroscopic and histologic study. PMID- 8446351 TI - Postoperative candida keratitis treated successfully with fluconazole. PMID- 8446352 TI - Transscleral Nd:YAG laser cyclodestruction. PMID- 8446353 TI - Management of extruded enucleation implants. PMID- 8446354 TI - Distinguishing hydrodissection and hydrodelineation. PMID- 8446355 TI - "Guarded filtration procedure"--not "trabeculectomy". PMID- 8446356 TI - "Guarded filtration procedure"--not "trabeculectomy". PMID- 8446357 TI - Informed choice, not informed consent. PMID- 8446358 TI - Planned combined I-125 plaque irradiation and indirect ophthalmoscope laser therapy for choroidal malignant melanoma. AB - We studied the short-term impact of planned sequential episcleral I-125 plaque irradiation and indirect ophthalmoscope laser therapy in a series of 25 patients with choroidal or ciliochoroidal malignant melanoma. In a case-by-case matched comparison study, we evaluated the relative local regression of tumors which did and did not receive planned supplemental laser therapy following plaque treatment. The tumors treated with supplemental laser regressed substantially faster and more completely than those treated by plaque alone. Planned sequential I-125 plaque irradiation combined with indirect ophthalmoscope laser therapy appears to be a more effective local-tumor treatment than plaque radiotherapy alone. PMID- 8446359 TI - Survival of patients and metastatic and local recurrent tumor growth in malignant melanoma of the uvea after ruthenium plaque radiotherapy. AB - A series of 100 consecutive patients treated by ruthenium plaque radiotherapy for uveal malignant melanoma from 1981 to 1991 was studied to evaluate local recurrences, metastases, and melanoma-specific mortality. Follow up ranged from 1.0 to 10.1 years (mean, 3.3; median, 3.0 years). Local relapse was observed in 19 patients from 0.1 to 2.7 years (median, 0.7 years) after therapy. Six of these eyes were enucleated. The 5-year probability of local tumor control was 59%. Seven patients with local relapse developed metastasis 0 to 4.3 years (median, 1.4 years) later. Altogether, 18 patients developed metastases 0.9 to 4.6 years (median, 2.0 years) after the irradiation, and 15 of them died of melanoma 5 days to 3.3 years (median, 0.5 years) after detection of metastases. The 5-year probability of metastasis not developing was 61%. The overall 5-year survival was 78%, excluding causes other than malignant melanoma. Large tumor size and anterior tumor location, with or without ciliary body involvement, predicted poor prognosis both in terms of local growth, metastases, and melanoma-specific mortality. Local recurrent tumor growth was associated with a significant increase in metastasis but a nonsignificant increase in melanoma-specific mortality. PMID- 8446360 TI - Secondary dye testing of the lacrimal system. AB - Using the Olympus PF-22 angioscope to examine the inferior meatus during secondary dye testing of the lacrimal system, I evaluated the efficacy of the secondary dye test to localize partial or functional obstruction of the upper or lower lacrimal excretory system. Secondary dye testing was positive (dye present in the nose) in 12 of 13 lacrimal systems (92%) with functional nasolacrimal duct obstruction, in 7 of 8 (89%) with involutional ectropion, and in 4 of 5 (80%) with facial nerve palsy. Secondary dye testing was negative in the 1 lacrimal system with canalicular stenosis and in 5 of the 6 (83%) with punctal stenosis. Secondary dye testing is helpful in differentiating punctal or canalicular stenosis from functional nasolacrimal duct obstruction; however, it cannot help differentiate ectropion or facial nerve palsy from functional nasolacrimal duct obstruction. PMID- 8446361 TI - Using high-frequency ultrasound to characterize intraocular foreign bodies. AB - We scanned uniformly-sized particles of brass, aluminum, glass, and plastic at ultrasonic frequencies of 10 and 50 MHz to determine the effects of material type and transducer frequency on the ultrasonographic appearance of these particles. The particles were scanned in vitro against both anechoic and echoic backgrounds and in vivo, implanted in the angle of rabbit eyes. Both the metals and glass produced reverberations against an anechoic background; the plastic particles appeared as discrete objects, with no reverberations. Against an echoic background, the plastic particles created prominent shadows, while the metal ones did not. When placed in the angle of a rabbit eye, with the exception of the plastic at 10 MHz, all the materials could be differentiated from surrounding tissues at both frequencies. However, the appearance of the foreign body and the surrounding tissues, as well as their exact location and size, were most obvious with the 50-MHz system. In general, the particles produced more reverberations at 10 than at 50 MHz, and more prominent shadowing at 50 than at 10 MHz. In summary, high-frequency imaging enabled superior characterization of all the particles. PMID- 8446362 TI - Modification of ischemia/reperfusion-induced ion shifts (Na+, K+, Ca2+ and Mg2+) by free radical scavengers in the rat retina. AB - We investigated the contribution of scavenging of oxygen free radicals to retinal ion contents during ischemia and reperfusion with the use of superoxide dismutase (SOD, Sigma), allopurinol (Sigma), EGB 761 (extract of Ginkgo biloba, Tanakan, IPSEN, Paris, France) and allopurinol plus EGB 761 in the rat. SOD (15,000 U/kg/day), allopurinol (50 mg/kg/day), EGB 761 (100 mg/kg/day) and allopurinol (50 mg/kg/day) plus EGB 761 (100 mg/kg/day) were administered for 10 days, respectively. Then, the eyes were subjected to 90 min of ischemia followed by 4 and 24 h of reperfusion, respectively. Retinal Na+, K+, Ca2+ and Mg2+ contents were measured by atomic absorption spectrophotometry after the washing out of blood and extracellular fluid from the vasculature. SOD, EGB 761 and the combination of EGB 761 with allopurinol significantly reduced the ischemia/reperfusion-induced Na+ and Ca2+ accumulation and K+ loss in ischemic/reperfused retinal tissue. Allopurinol alone failed to reduce the maldistribution of Na+, Ca2+ and K+ induced by ischemia/reperfusion in the retina. Neither intervention inhibited the cell Mg2+ loss which was observed during ischemia and reperfusion. Despite the responsible mechanisms remaining controversial, many studies confirmed that ischemia/reperfusion could trigger very sudden metabolic, electrophysiologic, morphologic and functional changes. There is general agreement that major ionic shifts are implicated; what triggers these changes is unclear, although many investigators believe that free radicals and oxidant stress may be important.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446363 TI - Effects of melatonin and haloperidol given via vortex vein on the intraocular pressure. AB - Melatonin injected into the vortex vein of a rabbit eye produced an increase in intraocular pressure (IOP) which lasted for up to 5 h. Injection of haloperidol caused a decrease in IOP; this effect was totally reversed by melatonin. It is probable that these effects are caused by physiological antagonisms. Injection of the mu opiate agonist (D-ala2-n-methyl-ph2-gly5-ol) enkephalin caused a decrease in the IOP of artificially ventilated rabbits and a decrease in melatonin levels in iris, iris root-ciliary body, and retina of the rabbit eye. Melatonin levels did not decrease after anesthesia with rompunketamine. It is probable that the decrease in melatonin levels is specific to certain classes of opioids, and endogenous opioids may play a role in the regulation of ocular melatonin levels and hence IOP. PMID- 8446364 TI - Differences in naphthalene cataract formation between albino and pigmented rat eyes. AB - The progression of naphthalene cataracts induced in Brown-Norway rats and Sprague Dawley rats was compared. The quality of lens changes was basically the same in both strains. However, the cataract progression in Brown-Norway rats showed regularity and was fast as compared with the progression in Sprague-Dawley rats. The cataract development could be divided into three stages. Stage 1: formation of water clefts below the anterior lens capsule (shallow cortex) was observed as the initial change; stage 2: these water clefts extended into the deeper cortical layers, and a semicircular opaque band at the deeper cortical region becomes visible; stage 3: a retroillumination image revealed a ring shadow formation - slit image observation showed wedge-shaped cortical and deeper cortical zonular opacification as the final stage. The expression of these three stages in Sprague Dawley rats is less uniform and timely delayed as compared with Brown-Norway rats. PMID- 8446365 TI - Tear anti-Chlamydia antibodies in males with chlamydial urethritis. AB - Conjunctival Chlamydia trachomatis was studied in 50 males with chlamydial urethritis. Conjunctival samples from 49 patients were negative for chlamydial antigen by enzyme immunoassay. However, tear anti-Chlamydia IgA antibodies were found in high titers (> or = 400) in 20 out of the 50 patients. Secretory IgA against Chlamydia in corresponding titers was found in 8 patients. The titers differed significantly from those of the 22 negative control subjects. IgG antibodies were not detected. Tear anti-Chlamydia IgA antibodies are not diagnostic for chlamydial conjunctivitis, but occur concomitantly in patients with chlamydial urethritis. PMID- 8446366 TI - Relationships between acetone, cataracts, and ascorbate in hairless guinea pigs. AB - Acetone is one of the most commonly used industrial solvents. Recent literature indicated that in guinea pigs, but not rabbits, acetone is cataractogenic and that elevated acetone exposure is also associated with depressed aqueous ascorbate levels. Other work indicated that aqueous and lens levels of ascorbate are closely linked and that depressed ascorbate status is related to cataract. Taken together, these papers suggested that acetone exposure, depressed ascorbate levels, and cataract are related, possibly causally. While the possibility that acetone is cataractogenic presented a major health concern, it also presented an opportunity to develop a new model of cataract in which hypotheses regarding anticataractogenic effects of ascorbate could be tested. Albino hairless guinea pigs are immunocompetent animals derived from albino Hartley guinea pigs. Animals were fed diets containing low (4.9 mg/day) and high (55 mg/day) levels of ascorbate. This resulted in distinct groups of animals, one with high tissue ascorbate levels and the other with low, but nonscorbutic ascorbate levels. The tissue levels of ascorbate and the relationship between tissue ascorbate levels and dietary intake indicate that with respect to ascorbate uptake, transport, and concentration, these animals are identical to the standard albino Hartley animals. Daily exposure to acetone was extended for 6 months, with a total applied dose of 65 ml. Absorption of the solvent was maximized by the use of hairless animals. Despite exposure of the animals to higher levels of acetone, in no case (n = 20) were cataracts observed over a 2-year period. This is consistent with results using rabbits.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446367 TI - Characterization of esterases involved in the hydrolysis of dipivefrin hydrochloride. AB - We characterized the interaction of the prodrug dipivefrin hydrochloride (DPE) with esterase activity in the rabbit cornea. The esterases which were identified included: (1) cholinesterase, (2) acetylcholinesterase, (3) a mixture containing carboxylesterase, acetylesterase and arylesterase, and (4) a non-specific esterase. DPE suppressed all of their activities as well as that of the mixture containing carboxylesterase, acetylesterase and arylesterase, and a nonspecific esterase. However, its effect on cholinesterase was larger than on any of the other activities, suggesting that DPE is a better substrate for cholinesterase than for any of the other esterases. These measurements along with those of substrate-dependent inhibition of 14C-DPE hydrolysis indicated that the DPE esterase interaction was competitive based on changes in the apparent Km values which were extracted from Lineweaver-Burk plots of esterase activity. The substrate for cholinesterase competed with DPE most strongly among substrates. These results seem to suggest that DPE is hydrolyzed by various corneal esterases, mainly cholinesterase. PMID- 8446368 TI - Growth factors in vitreous and subretinal fluid cells from patients with proliferative vitreoretinopathy. AB - Mechanisms accounting for the development of proliferative vitreoretinopathy (PVR) in patients with rhegmatogenous retinal detachment remain poorly understood. In a previous study, we found the presence of various growth factors in preretinal membranes that were surgically removed from patients with PVR. The present immunohistological study was undertaken in intravitreal and subretinal fluid cells from patients suffering from PVR in various stages of development, in order to seek the presence of 4 growth-promoting factors for retinal pigment epithelial cells: acidic fibroblast growth factor (FGF), epidermal growth factor (EGF), insulin-like growth factor type I (IGF-I) and transforming growth factor beta (TGF-beta). Results were quite similar in vitreous and subretinal fluid. Acidic FGF was found in all vitreous and subretinal specimens, in 30-100% of the examined cells. Immunoreactivity for EGF could be found in 53% of intravitreal cells and 69% of subretinal fluid cells. Positive cells were seen in all vitreous specimens and in all but 1 of the subretinal fluid specimens. IGF-I-containing cells were present in 13 of 15 vitreous specimens and in 18 of 20 subretinal fluid samples (mean percentages of reactivity in positive specimens 70% and 78%, respectively). In contrast, TGF-beta 1 reactivity was found in only 8 of 15 vitreous specimens and in 11 of 20 subretinal samples. Mean percentages of reactive cells were 30% and 50%, respectively. These results suggest that several growth factors could be involved in the proliferation and migration of retinal pigment epithelial cells during the course of PVR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446369 TI - Inhibition of interphotoreceptor retinoid-binding protein-induced uveitis by monoclonal antibodies. AB - Immunization of Lewis rats with interphotoreceptor retinoid-binding protein (IRBP) resulted in development of uveoretinitis in 100% (12/12) of the animals so injected. In the present study, we attempted immunotherapy of this intraocular inflammation using the monoclonal antibodies anti-I-A and anti-I-E. The antibodies were injected 1 day before and on days 1 and 2 after IRBP sensitization, and the animals were killed 16 days later. Anti-I-A treatment inhibited the disease in 83% (10/12) of the animals, while anti-I-E antibodies resulted in inhibition of the disease in 67% (8/12) of the animals. All rats injected with preimmune IgG (control animals) developed uveoretinitis. The anti-I A and anti-I-E antibodies exerted a specific suppressor effect on the immune response of these animals. Thus, anti-I-A and anti-I-E antibodies administered at the time of antigen priming abolished the immune function and inhibited the development of autoimmune uveitis. PMID- 8446370 TI - Refractive indices of the rat retinal layers. AB - The refractive indices in various rat retinal layers, based on the total dry mass concentration, ranged from 1.369 to 1.385. The ratios of the refractive indices of neighboring retinal layers were near unity. This finding suggests that light passes through the rat retina without much refraction. PMID- 8446371 TI - Contrast sensitivity in elderly subjects with a diagnosed ocular disease. AB - In a random sample of 3283 subjects, 1266 right eyes and 1334 left eyes were diagnosed as having one of the following: age-related macular degeneration (ARMD), cataract, or glaucoma. In this same sample 1369 right eyes and 1312 left eyes had no ocular disease. All eyes had their contrast sensitivity measured using the Arden-type gratings manufactured by The American Optical Corporation. This is a large sample survey and although prevalence rates for the diseases examined may be inferred, this must be carried out with caution. I found for those eyes where the disease interfered with the integrity of the retina (ARMD, glaucoma) the mean contrast sensitivity scores were higher, in the middle and upper frequencies, than for those eyes with lens opacities. For frequencies above 0.4 cpd contrast sensitivities associated with diseased eyes were significantly (p < 0.001) reduced when compared to the same measures obtained on nondiseased eyes. PMID- 8446372 TI - Residual aniseikonia among patients fitted with one or two intraocular lenses (pseudophakic corrections) AB - In the presence of one or two intraocular lenses (IOL's; pseudophakic corrections) or in the presence of naturally occurring or developmental anisometropia (due to a tumescent cataract) some induced or residual refractive aniseikonia is usually encountered. We wish to call this problem to the attention of the optometric practitioner. We provide a discussion of the resultant aniseikonia and simple rules of thumb for management of such patients with refractive aniseikonia. Aniseikonia in these patients may be less important than once had been suggested, but certainly it is more significant than it is currently being considered. Use of personal computers to calculate this aniseikonia makes appropriate correction relatively easy and readily applicable. PMID- 8446373 TI - Optical aspects of tolerances to uncorrected ocular astigmatism. AB - We approached the question of the visual tolerance to uncorrected astigmatism by exploring the changes in the retinal diffraction images brought about by astigmatism, as a function of spherical focus. Consideration of the Rayleigh and Marechal wavefront criteria and of the changes in ocular modulation transfer function (MTF) broadly supports a value of 0.25 DC as a practical tolerance limit for uncorrected astigmatism. This study underlines the limitations of a geometrical optical approach to this problem in particular, and shows that the concept of the circle of least confusion may be misleading. PMID- 8446374 TI - An image analyzer study of central serous chorioretinopathy. AB - The angiographic characteristics of central serous chorioretinopathy (CSC) were studied by analyzing digitalized angiograms with an IMAGEnet system. We determined the type of leak, its location, and its distance from the fovea and from the center of the detachment. Round leaks were located farther from the detachment center and farther from the fovea than smokestack leaks. Detachments tended to center on the fovea regardless of the leak to fovea distance. These findings suggest that for serous detachment of the sensory retina to develop and be maintained, there must be a diffuse dysfunctional area of retinal pigment epithelium and a focal leak. PMID- 8446375 TI - Stability of oculomotor fixation as a function of target contrast and blur. AB - Previous studies have shown that changes in target parameters, such as luminance, color, size, and shape exert little effect on the stability of fixation, measured as the standard deviation of eye positions over several seconds of fixation. In this study, we investigated the effect of target contrast and dioptric blur on the stability of fixation in five normal subjects. The horizontal positions of both eyes were assessed by infrared limbal tracking while the subjects fixated binocularly for 20-s intervals on a cross-shaped target at 2 m. Across subjects, the mean stability of fixation on a high contrast target worsened significantly from 8.9 to 12.0 min arc with fixation through increasing amounts (0 to 4 D) of dioptric blur. However, without blur there was no statistically significant effect on fixation stability of varying the target contrast from 7 to 84%. The variability of vergence was not significantly influenced in either condition. Like other target parameters investigated in previous studies, dioptric blur and contrast have relatively inconsequential effects on fixation stability, indicating that the signals used to control fixation are largely independent of stimulus parameters. Practically, the findings suggest that when patients' eye movements are recorded for clinical reasons, the results are unlikely to be affected seriously by the presence of residual refractive error. PMID- 8446376 TI - Readability of ophthalmic literature. AB - The Gunning Fog Index and the Flesch Reading Ease Formula were used to analyze the readability of a sample population of optometric and ophthalmological journals. The results suggest that ophthalmological journals are significantly less readable when compared to optometric publications. Specific findings are reported along with the limitations of the study. PMID- 8446377 TI - A prospective study of treatment of accommodative insufficiency. AB - Prepresbyopic patients with reduced accommodative amplitude (accommodative insufficiency) are commonly seen in optometric practice. Treatments include accommodative therapy and plus reading lenses. We did a prospective study of the effects of vision therapy and plus reading lenses on 15 patients (mean age 21.87 +/- 9.66 years) with accommodative insufficiency; presumed etiologies included head trauma (6 patients), thyroid disease (3 patients), seizures (1 patient), toxoplasmosis (1 patient), and idiopathic causes (4 patients). A 7-question scaled response pre- and post-treatment questionnaire assessed symptoms of two groups, vision therapy (idiopathic only) and progressive addition lenses (all patients). No idiopathic patient improved after 3 weeks of accommodative therapy. Progressive lenses with a near addition of + 1.00 or + 1.25 were then prescribed. Questionnaire results, which indicate that near additions provided more relief of symptoms than vision therapy for treatment of accommodation insufficiency, underscore the need for careful examination of prepresbyopic patients to determine those who would benefit from a near addition. PMID- 8446378 TI - Role of lasers in eye care. AB - This review discusses the role of lasers in eye care under five headings: Absorption of laser radiation by ocular tissues. Types of lasers include: ruby, argon, gas, organic dye, krypton, Nd:YAG, excimer, and infrared. Applications of lasers for examining the eye include: laser refraction, determining visual acuity by laser fringes, measuring retinal blood flow, scanning laser ophthalmoscopy and tomography, measuring aqueous flare, ocular holography, measuring retinal absorption, measuring visually evoked potentials, and measuring corneal sensitivity. Applications of laser radiation for ocular surgery include: photocoagulation, destruction of tumors, reattaching the retina, treating glaucoma by producing an iridotomy or by trabeculoplasty or by cyclodestruction. Lasers can be used to remove surface irregularities or superficial opacities from the cornea or eyelids. Other uses are for producing a capsulotomy and for altering corneal curvature as a means of correcting ametropia. Potential adverse effects of laser radiation on the eye are summarized. PMID- 8446379 TI - Schirmer test. I. A review. AB - Since its introduction by Schirmer in 1903, the Schirmer test has been widely used for the assessment of the adequacy of tear production. Although the faults of the Schirmer test have been well documented, it is nevertheless still being used to assess tear production, especially in the diagnosis of keratoconjunctivitis sicca (KCS) and for screening potential contact lens wearers. We summarize the findings and conclusions of some of the previous studies. PMID- 8446380 TI - Schirmer test. II. A clinical study of its repeatability. AB - In most parts of the world, the Schirmer test (ST) is still the main test used by optometrists for the assessment of tear adequacy in the screening of potential contact lens wearers and as an aid in the diagnosis of "dry" eye. We tested the reliability of a 1-min ST in nine normal Hong Kong-Chinese (HK-Chinese) subjects during five to seven visits over a period of 2 weeks. For 4 of the subjects, the test consistently measured 0 mm/1 min, and 68% of the test results were less than 6 mm/1 min, a value suggested as the lower limit for normal asymptomatic eyes. The results obtained were inconsistent and it is concluded that the ST is unreliable and of little clinical value in this population. PMID- 8446381 TI - Induced prismatic effect in spectacle prescriptions sampled in Saudi Arabia. AB - We determined the prevalence of prescription glasses-induced prismatic effect among a sample of 100 patients in the Kingdom of Saudi Arabia. All the glasses sampled had a certain degree and type of induced prismatic effect. A small percentage (5%) of the subjects complained about their glasses. Prism adaptation is thought to be the reason why the number of patients complaining about improperly fitted glasses does not reflect the frequency of the problem. Simple ways of eliminating these inaccuracies are suggested. PMID- 8446382 TI - Visual losses in early age-related maculopathy. AB - Age-related maculopathy (ARM) can be considered a transition from normal retinal changes to pathological processes. It is important to recognize patients who have progressed beyond a normal state in order to provide appropriate clinical management. This pilot study considers the clinical dilemma of diagnosing and monitoring early ARM. We carried out a controlled study and tested the visual functions of 11 pre-ARM (PARM) and 11 early ARM subjects. Apart from compromised visual acuity, losses in central visual field, color vision, and visual adaptation were also recorded in our ARM subjects. We found a low contrast (LC) Amsler grid to be most sensitive to central field defects and that the desaturated panel D-15 gave too many false positives among normal elderly subjects. Our results indicate foveal sparing in early ARM and question the capacity of acuity assessment to reflect early functional changes adequately. A clinical battery is recommended to detect and monitor ARM. PMID- 8446383 TI - Contrast sensitivity in 24- and 36-month-olds as assessed with the contrast sensitivity card procedure. AB - We used a new card procedure to evaluate binocular contrast sensitivity (CS) in 24- and 36-month-old children. The test consists of 40 large (50 by 28 cm) matteboard cards, each of which contains a sine wave grafting with 1 of 5 spatial frequencies (0.4, 0.8, 1.6, 3.2, and 4.8 cpd at 80 cm) and with 1 of 8 contrast levels [from 33% (CS = 3) to 0.4% (CS = 260)]. Estimates of subjects' CS to each spatial frequency were obtained with a modified forced-choice preferential looking (FPL) technique similar to that developed for the Teller Acuity Cards (TAC). All 36-month-olds and 74% of the 24-month-olds completed the entire procedure in an average of 12 min per child. For both groups, the shape of the mean constant sensitivity functions (CSF's) resembled the characteristic inverted U shown by normal adults, except that the toddlers' functions were shifted to lower contrasts and spatial frequencies. Combined with previous results, it appears that the CS cards hold promise as a time-efficient means of assessing CS in infants and young children, and may provide the prototype for a clinical tool to help detect early visual and neurological dysfunction. PMID- 8446384 TI - Improved antiproliferative effect of cisplatin combined with phorbol ester. An in vitro study. AB - A combination of cisplatin (DDP) and tumor promoter phorbol ester 12-O tetradecanoylphorbol-13-acetate (TPA) or nonphorboid tumor promoter mezerein (MEZ) were tested by 5-bromo-deoxyuridine (BrdU) and 3,4,5-dimethylthiazol-2,5 disphenyl-tetrazolium bromide (MTT) assays for their antiproliferative actions. DDP and TPA showed a synergistic effect at concentrations where the single drug did not show any significant action. The BrdU assay seemed to be more sensitive than the MTT assay in measuring these drug effects. Epidermal growth factor (EGF) receptor number and affinity on treated cells were not altered as showed by 125I EGF-receptor assay. EGF stimulation experiments suggested an inhibition of receptor-mediated signal transduction by TPA. PMID- 8446385 TI - Effects of the holmium:YAG and erbium:YAG lasers on endotracheal tubes. AB - Endotracheal tube (ET) fire is the most frequent complication arising with laser surgery in the upper aerodigestive tract. No data are available about the safety of commonly used ETs when used with recently developed high-energy pulsed lasers, working with only a minimal thermal component but mainly photoablative. A comparative in vitro study was performed with three types of endotracheal tubes to assess their resistance to wall and cuff damage by the laser beams of two pulsed infrared solid-state lasers. ET perforation was attempted with the erbium:YAG (lambda = 2,930 nm) and holmium:YAG (lambda = 2,120 nm) lasers. For all experiments, a repetition rate of 5 Hz was used. The 2.5-microseconds holmium:YAG pulses were coupled into a nylon fibre of 400 microns diameter. The 2.0-microseconds erbium:YAG laser pulses were applied to ETs through a lens system providing a spot size diameter of 200 microns. Polyvinyl chloride and silicon ET segments were exposed to laser pulse energies from 97 to 500 mJ in the presence of different anaesthetic gas mixtures. The time from the onset of exposure to tube perforation was recorded. Thermal gradients following laser application were measured. Laser exposure was continued for up to 90 s, unless tube ignition occurred. At all energy levels tested, the photo-ablative mechanism of laser-tube interaction, with few thermal components, led to laser-induced tube ignition if an FiO2 > 21% for the holmium:YAG and 34% for the erbium:YAG laser was established. With increasing pulse energies, ET segments ignited sooner. MLT tubes performed best in the present safety test. PMID- 8446386 TI - Barotrauma in Boeing 737 cabin crew. AB - Several aircrew members of a Boeing 737 aircraft were referred to our department because they suffered from a barotrauma. The fast rate of pressure change during the descent of a Boeing 737 aircraft, as compared to the Boeing 747, DC-10 and Airbus 310 aircrafts, is most likely the cause of the development of the barotraumata. PMID- 8446387 TI - Bilateral facial paralysis secondary to lymphoma. AB - We report a patient with bilateral facial palsy due to a non-Hodgkin lymphoma. He was initially diagnosed to have a facial paralysis of unknown aetiology. Three months after this original diagnosis, he developed a non-Hodgkin lymphoma which was treated successfully with chemotherapy, and his palsy consequently returned to normal. PMID- 8446388 TI - Brain herniation into the mastoid in a normal hearing ear. AB - A cluster of right temporal lobe abscesses in a 40-year-old male originated from an endaural brain hernia affecting the mastoid only, without direct contact with the ossicular chain. In infancy, antrotomy had been performed. Otologic signs were sparse, hearing was normal. Computed tomography of the temporal bone showed homogenous clouding of the retrotympanal spaces and a defect of the tegmen antri. Treatment consisted of transmastoid debridement, reduction and duraplasty with fascia lata. PMID- 8446389 TI - Human Reissner's membrane in patients with age-related normal hearing and with sensorineural hearing loss. AB - Morphological features of Reissner's membrane were investigated in 6 patients with age-related normal hearing (ARNH) and in 4 with sensorineural hearing loss (SNHL) stemming from various causes. The membrane consisted of an epithelium, a basement membrane and a mesothelium with melanocytes. There were two major forms of epithelial cells: flat and rounded. In all specimens, the rounded cells formed whorls, clusters, strands and bands. The bands were wider and the whorls larger in the basal turn and decreased gradually in size toward the apex. The number of melanocytes was 2-4 times higher in both the upper half of the basal turn and the lower half of the middle turn than in the rest of the turns. In specimens from patients with SNHL, whorls and clusters were both more numerous and larger, and the number of melanocytes was higher in the upper half of the middle turn and in the apical turn than that in the ARNH group. Ultrastructural examination of epithelial and mesothelial cells as well as of melanocytes showed more pronounced cellular degeneration in patients with SNHL than in those with ARNH. A possible correlation between structural alterations of Reissner's membrane and sensorineural degeneration is discussed. PMID- 8446390 TI - Experimental study of a frog semicircular canal nerve: influence of the initial cupular position. AB - The posterior semicircular canal of the frog was stimulated by mechanical endolymphatic flow toward either an ampullofugal (excitatory) or ampullopetal (inhibitory) direction. The magnitudes of the responses as the cupula was moved to various positions were compared. When the same amount of stimulus was given in the same direction, the responses were equal, regardless of the initial position of the cupula. PMID- 8446391 TI - Influence of elastase and hyaluronidase on the ciliary interconnecting systems in frog vestibular sensory cells. AB - Bullfrog vestibular end organs were incubated in frog Ringer's solution, hyaluronidase and elastase. When assessed by scanning electron microscopy, long time incubation in frog Ringer's solution caused damage to side links. Elastase caused severe damage to tip links with a slight alteration to side links. The glycocalyx of the hair cells decreased after incubation in elastase or hyaluronidase. Electrophysiological measurements showed a remarkable decrease in compound action potentials after the elastase treatment, while no change was observed after the long-time incubation in frog Ringer's solution or hyaluronidase. The results are in agreement with the hypothesis that tip links are involved in mechanotransduction, and side links keep the cilia arranged in a bundle. PMID- 8446392 TI - Effects of high-frequency sound on electrochemical potential using the single barrel method in guinea pigs. AB - There are only a few studies investigating the effects of ultrasound on hearing. This paper reports on an experimental investigation on the effect of the long time exposure to a moderate sound pressure level, high-frequency sound of 16 kHz on the guinea pig inner ear using electrophysiological methods. A decrease of the absolute value of negative potential was observed in the endocochlear potential (EP). The effects of high-frequency sound on EP and electrochemical potential could be explained by a change in the K+ permeability of hair cells. PMID- 8446393 TI - Auditory brainstem potentials in uraemia. AB - Evoked response audiometry was carried out to assess the viability of the auditory pathway in haemodialysed patients. The latency of the waves III and V and I-V interpeak latencies were significantly longer in the renal patients compared to the control group. The I-V interpeak latency was longer in 8 of our 13 patients than the upper limit (4.38 ms) in our laboratory. The possible cause for the central auditory dysfunction may be multifactorial, including the effect of metastatic calcifications, repeated occurrence of disequilibrium syndrome, or some small, molecular, toxic, metabolic substance. The significance of the different factors may vary among different haemodialysis centres. PMID- 8446394 TI - Cefetamet pivoxil in otitis media. AB - In this multicentre, open, randomized, parallel-group study, 270 children with acute otitis media aged between 1 and 15 years were randomized to receive either cefetamet pivoxil 10 mg/kg b.i.d. for 7 days (n = 134) or cefaclor 13.5 mg/kg t.i.d. for 7 days (n = 136). At the end of treatment, bacteriological cure occurred in 44/44 (100%) patients receiving cefetamet pivoxil and 24/28 (86%) patients receiving cefaclor. Clinical cure or improvement was experienced by 117/121 (97%) of patients receiving cefetamet pivoxil and 104/115 (90%) patients in the cefaclor group. Adverse side effects, mainly gastrointestinal disorders, occurred in 11% of patients in the cefetamet pivoxil group compared with 15% of patients in the cefaclor group. All adverse events were of mild or moderate severity and subsided rapidly after treatment. Premature treatment withdrawals occurred in 0.7% of patients who received cefetamet pivoxil and in 2.2% of those who received cefaclor. PMID- 8446395 TI - Accelerators and inhibitors to organizational change in a hospital. PMID- 8446396 TI - Vision, mission, and values: putting it together. PMID- 8446397 TI - Evaluating your mission: a practical approach to developing and assessing a facility's organizational culture. AB - Health care organizations must define and establish a core set of expectations about behaviors and values, which could give health care providers and administrators the guidance needed for the successful implementation of continuous quality improvement principles. This article describes how the Division of Mission Effectiveness continually assesses and takes actions to improve mission effectiveness within Alexian Brothers Health Systems. Mission effectiveness or an organization's "mission health," as operationalized in terms of values and behaviors, is assessed by an annual employee "opinionnaire." Once results are in, an "operational mission plan" is developed with objectives on how to improve mission effectiveness for the following year. PMID- 8446398 TI - Clinical quality improvement: getting physicians involved. AB - Through support from the Robert Wood Johnson Foundation through its program, "Improving the Quality of Hospital Care," the Vermont Program for Quality in Health Care (VPQHC) has developed a quality improvement model that hastens learning through knowledge sharing. Using guidelines and other quality improvement techniques, VPQHC works with hospitals and practitioners to improve not only hospital processes of care but also clinical management. This article describes the concepts driving the program, using an example, and describes the program's success in involving physicians in the process. PMID- 8446399 TI - The transition from quality assurance to continuous quality improvement in ambulatory care. AB - The transition of quality assurance to continuous quality improvement (CQI) in ambulatory care organizations requires careful planning and consideration of efficiency. Ambulatory care organizations must maintain indicators to measure activities, sample the multiple encounters of ambulatory care, and truly change their internal culture. This article provides practical information that persons involved in quality management can use to plan CQI processes in ambulatory care. PMID- 8446400 TI - Leading the transformation in health care quality through improved performance. PMID- 8446401 TI - [Familial dilated cardiomyopathy]. AB - The author surveys the literature and gives a state of art of familial dilatative cardiomyopathy including his own experience. In the past two decades, III familial dilatative cardiomyopathy cases have been encountered in 30 families in their own material, which means a 21.5 percent incidence rate as concerns the total number of dilatative cardiomyopathy patients. The inheritance pattern was autosomal dominant in the majority of the cases. Both cardiomegaly (20 vs 29.6 ys) and the complaints (29.9 vs 37.6 ys) displayed an earlier onset in familial dilatative cardiomyopathy than in the nonfamilial form. The characters of the signs and symptoms did not differ otherwise between the two groups. Significant differences were observed between the two groups in the progression of the disease: the five-year survival rate after the onset of the symptoms was 23.1 percent in the familial cases and 52.1 percent in the non-familial form (p = 0.026). PMID- 8446402 TI - [Attempt at prevention of chronic otitis media in childhood]. AB - Two diseases are considered by the author as fundamental ones in the development of chronic otitis media. These are the mastoiditis and the tube auditory dysfunction. Both diseases occur the most frequently in age-groups which can be determined well. The mastoiditis occurs most frequently in infancy and in baby age, while the auditory tube dysfunction occurs between the age of 3 and 7. Main trend of the prevention should be focused on these two diseases. By recovering from mastoiditis in time, recognition of the tube dysfunction and providing the ventilation of the middle ear, the definitive destroy of the tympanic membrane, the auditory ossicle and the development of chronic otitis media can be prevented. PMID- 8446403 TI - [Pathogenic properties of coagulase-negative staphylococci in experimental infections]. AB - The frequency of persistence of three Staphylococcus epidermidis, Staphylococcus haemolyticus and Staphylococcus saprophyticus strains, respectively, was studied in BALB/c mice at the 10th day of intraperitoneal (ip) challenge. 245 out of 416 mice survived after infections with four bacterial suspensions of different colony forming units (CFU) of each strain. Staphylococci persisted in 61 mice (24,9%). The main sites of persistence were the kidneys, while cocci were rarely isolated from the spleen and the liver. S. epidermidis persisted with a significantly higher rate than the other two species, because S. epidermidis in 28,8%, S. haemolyticus in 4,9%, and S. saprophyticus in 3,6% were reisolated from the organs of the respective infected and surviving animals. The organ persistence was proportional to the amount of bacteria injected. The persistence resulted in subacute microabscesses in the organs. Reisolates of persisting bacteria remained stable in phenotype and genotype concerning antibiotic resistance patterns and biochemical activities for the taxonomic implication, whereas cell surface properties characterizable with phage types altered considerably during persistence. It is concluded that cocci of all three Staphylococcus species are invasive and can persist to a certain extent in the organs of animals with normal immune system, too, after artificial inoculation into the peritoneum i. e. to the serosal surfaces. PMID- 8446404 TI - [Critical review of the financing system of Prospective Payment/ Diagnosis Related Groups, based on experience in the United States of America]. AB - The authors survey the causes and results of introduction of DRG system. The main cause for the introduction of this system was the sudden rise of costs experienced in the early 80ties. The introduction was followed by a manifest slowing down of cost rise, then again it started to increase a little. The internal efficiency of the institutions improved, the most outstanding example for that was the shortening of the average nursing time, the increase of the rate of outpatient consultations. The absolute value of costs did not decrease in spite of that because on the one hand medical technics are continuously developing and getting more expensive, on the other hand health care cannot as well be independent from the general processes of economy. Summarized it can be stated that the introduction of the DRG system in the USA did achieve its goal because it was able to slow down the rise of costs without serious operation disorders. PMID- 8446405 TI - [Successful delivery following continuous cytostatic therapy of a leukemic pregnant women]. AB - The authors report about a successful labour and delivery after pregnancy with chronic myeloid leukemia treated with hydroxyurea. The haematological state of the mother could be well balanced with this cytostatic drug. The fetus was in a good condition during the whole pregnancy. At term a healthy newborn delivered with no signs of malformation or haematological disease. At a follow up visit 6 weeks after delivery the state of the mother and the newborn was satisfactory. The incidence of leukemia and pregnancy is rare. The creation of a central registry to pool experiences and data would help define optimum treatment regimens for this group of patients. A close cooperation among haematologist, obstetrician and pediatrician is emphasized. PMID- 8446406 TI - [The journal Orvosi Hetilap on the road to preservation of traditions as well as modernization]. PMID- 8446407 TI - [Remembering Lajos Markusovszky]. PMID- 8446408 TI - [History of the first cholecystectomy]. PMID- 8446409 TI - [Evaluation of hemodynamic parameters in patients with right ventricular infarction during rehabilitation]. AB - Hemodynamic data in 43 patients with right and left ventricular infarction and 39 with left ventricular infarction were compared. Right atrial pressure, pulmonary capillary wedge pressure, mean pulmonary artery pressure, left ventricular end diastolic pressure before and after ventricular angiogram, cardiac index, left ventricular stroke volume index, right ventricular stroke work index were evaluated, as well as ratios of right atrial and pulmonary capillary wedge pressure, right and left ventricular end-diastolic pressure, right ventricular end-diastolic and pulmonary capillary wedge pressure, left ventricular ejection fraction calculated from left ventricular angiogram, Berentey's score, and cardiac volume index. Using ONEWAY analysis there was no significant difference between the two groups in period of rehabilitation. In 15 patients with right ventricular infarction regression of ECG changes was observed in lead V3R also without significant influence on hemodynamic data. PMID- 8446410 TI - [Allergologic study of the pathogenesis of atopic dermatitis in infancy and childhood]. AB - The authors present the results of allergologic investigations in 54 infants and children with atopic dermatitis. To demonstrate the food and inhalative allergies, which are most important etiologic factors in this disease, different methods have been administered. Besides these in vitro and in vivo methods oral food challenges were done to verify the real causative role of the food in question. Food allergy only was verified in 16 cases, 12 patients were suffering in inhalative allergy. Both kind of allergens produced reaction in 19 cases. Among the foods hen egg caused sensibilization most frequently, among the inhalants the house dust mite. In analysing the results the authors want to demonstrate the combined allergic etiology, of atopic dermatitis. PMID- 8446411 TI - [Multiple urologic tumors in autopsy material]. AB - In autopsy material of the Department of Pathology at the Albert Szent-Gyorgyi Medical University in 16.8% of kidney cancers, in 12.5% of urinary bladder cancers and in 21.8% of prostatic cancers were second primary malignant tumours observed in the urinary system or in other organs. The cause of the relatively frequent tumour-associations can partly be explained with the high average age (72 years). The uropoetic cancers were in association with lung cancers (role of tobacco smoking?), gastrointestinal tumours (role of genetic or dietary factors?); and the prostatic carcinomas with urinary bladder cancer and hematologic malignancies. In our material testicular cancers were never associated with other malignancies. PMID- 8446412 TI - [Successful shock wave monotherapy of coral-shaped calculi in the kidney calix]. AB - Authors reported about two patients with staghorn calculi, who have been treated by extracorporeal shock wave monotherapy by Direx Tripter-X-1 Lithotripter. They used in the first case percutaneous nephrostomy, in the second double J catheter as auxiliary method. Patients were treated 3 and 4 time, and they were stone free at three month follow up. PMID- 8446413 TI - [H2 exhaling test and enteral feeding]. PMID- 8446414 TI - [Quo vadis, Chirurgia?]. AB - After an overview of the last one and a half century of the golden age of classic surgery the author discusses the problem of specialization in general surgery. Due to the basic change of the nature of some diseases and to the development of medical and endoscopic treatment some of the routine surgical procedures have nearly disappeared: for example the partial gastrectomy in ulcer disease, the proximal gastric vagotomy itself, the transduodenal sphincterotomy, etc. This fact raises the question of education and post-graduation of young surgeons. Now the unlimited use of laparoscopic methods in abdominal surgery opens up new vistas. The recent state of art and the future is discussed, emphasizing the need of high ethical standard on the field of this entirely new surgery. PMID- 8446415 TI - [Adjuvant endocrine therapy--Zitazonium--in breast cancer]. AB - The authors deal with the problems of adjuvant therapy of breast cancer. They administrated Zitazonium in those postmenopausal women who had had positive axillary lymph nodes. In the course of analyzing the results, they calculated survival and tumor free survival with "life-table" method, while they used log rank probe and Mantel-Haenzel X2 probe for showing significance between the diagrams. The results were favourable, but no significant variance could be shown in the group treated with Zitazonium. If lymph nodes were proved to be negative the difference between the graphs were minimal. They refer to the question of steroid receptor determination and emphasize to take into account the biological markers when projecting adjuvant therapy. PMID- 8446417 TI - [Double supraventricular tachycardia and its surgical treatment]. AB - A case history is presented of a patient in whom a left-free-wall accessory pathway was surgically ablated to treat symptomatic Wolff--Parkinson--White syndrome. Subsequently, AV-nodal reentrant tachycardia became manifest. The patients's AV-nodal reentrant tachycardia was interrupted by Cox's discrete cryosurgical procedure. As a result of analysis of these cases of dual substrates for reentrant supraventricular tachycardia, ECG and electrophysiological means for differential diagnosis has been developed. These are discussed herein. PMID- 8446416 TI - [Serum keratan sulfate studies and their significance in the evaluation of cartilage degradation in degenerative and inflammatory joint diseases]. AB - Fragments of high density cartilage proteoglycan (aggrecan) are released during either the normal or pathological turnover of cartilage proteoglycans, which fragments diffuse into the synovial fluids and then appear in the serum. The keratan sulphate (KS; a glycosaminoglycan side chain of aggrecan) is resistant to enzymatic degradation, it has a relatively low clearance and has a "standard" serum level indicating the actual level of cartilage (proteoglycan) breakdown. Using anti-KS monoclonal antibody in ELISA (enzyme-linked immunosorbent assay), we measured serum KS levels in patients with different joint diseases. The highest KS content (595 ng/ml) was measured in the sera of patients with articular chondrocalcinosis (calcium pyrophosphate crystal deposition disease/pseudogout). Slightly lower KS levels were determined in osteoarthrosis (OA; 578 ng/ml) and much less in rheumatoid arthritis (RA; 421 ng/ml). All these patient groups (either with degenerative or inflammatory joint diseases) expressed slightly higher KS levels compared to control blood donors (295 ng/ml). However, there were remarkable variations between these diseased groups, i. e., KS levels in patients with RA were significantly lower than in patients with OA (p < 0.001) and this difference was more pronounced in rheumatoid patients with I II Steinbrocker stage (370 ng/ml) or in those treated with non-steroid anti inflammatory drugs (NSAIDs) (382 ng/ml). Keratan sulphate levels in RA patients chronically treated with corticosteroid (460 ng/ml) or auro-thiomalat (473 ng/ml) indicate that these drugs may influence the cartilage metabolism more effectively than the NSAIDs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446418 TI - [Secondary prevention and early detection (screening) of malignant tumors]. PMID- 8446419 TI - [To the "thinking man"]. PMID- 8446420 TI - Physician-assisted suicide: promoting rights or abuse? PMID- 8446421 TI - Who are you? PMID- 8446422 TI - Are we really ready for assisted dying? PMID- 8446423 TI - Defects in mitochondrial fatty acid oxidation: clinical presentations and their role in sudden infant death. AB - Defects in mitochondrial beta-oxidation may result in severe metabolic crisis after metabolic stress. The combination of hypoketotic hypoglycaemia and concurrent collapse of mitochondrial metabolic function may be very similar to that in Reye syndrome. Chronic effects on cardiac and skeletal muscle may be seen in some patients with defective long-chain fatty acid oxidation. Less common symptoms include peripheral neuropathy, pigmentary retinopathy, and failure to thrive with recurrent diarrhoea or vomiting. Collectively, such disorders are relatively common and their association with sudden infant death leads to a considerable demand for laboratory investigation. Currently the laboratory methods available are not capable of dealing with this demand in a rational and cost-effective manner and it is necessary to have careful clinically- and pathologically-based selection procedures if a useful service is to result. PMID- 8446424 TI - Diagnosis of mitochondrial fatty acid oxidation defects. AB - Inherited defects of mitochondrial beta-oxidation of fatty acids lead to hypoketotic hypoglycemia during prolonged fasting. Affected patients may present with episodes of a Reye-like illness or even sudden child death. The number of currently detected patients with medium-chain acyl-CoA dehydrogenase deficiency- the most common disease in this area--is indicative of a high frequency, possibly comparable to that of phenylketonuria. A comprehensive system of biochemical analyses is described, which enables the differential diagnosis of the various defects. An indispensable part of the diagnostic system is the gas chromatographic/mass spectrometric analysis of plasma and urinary organic acids. A correct diagnosis is a prerequisite for the installment of specific treatment. PMID- 8446425 TI - Diagnosis and therapy of organic acidurias. AB - Organic acidurias are a group of numerous inherited metabolic disorders with an involvement of different pathways of the amino acid, carbohydrate and lipid metabolism. Many diseases have their onset with an acute metabolic crisis in the newborn period. The most important diagnostic investigation is organic acid analysis of urine by gas chromatography-mass spectrometry. Because specific clinical signs are lacking, a selective screening procedure is recommended. Diagnosis and therapy should be aggressive, since prognosis of many disorders is related to early diagnosis and specific therapeutic measures. These include long term management with protein restriction, supplementation with special amino acid mixtures and carnitine. In our experience continuous arteriovenous hemofiltration has turned out to be a very effective detoxification method during acute metabolic crisis of the newborn. Long term follow up and therapy control is very important for the outcome of the patients. Measurement of odd long chain fatty acids (OLCFA) in erythrocyte membranes has proved to be a good control parameter of the metabolic condition of children with disorders of the branched-chain amino acid metabolism. PMID- 8446426 TI - Clinical manifestations of late onset cerebral storage disease: a case of metachromatic leukodystrophy. AB - Clinical symptoms, MRI of the brain and neuro pathological findings of a case with adult metochromatic leukodystrophy are presented. Clinically it is important to consider a possible late-onset manifestation of an inborn cerebral storage disease, when uncertain psychopathological symptoms are difficult to assign to well-known diseases. These cerebral storage diseases may appear as "juvenile behaviour disturbance" or "schizophrenia". The clinical suspicion may further be confirmed by simultaneous or subsequent neurological or ophthalmological symptoms. The definitive diagnosis is possible by biochemical or histopathological methods. MRI of brain and neuro pathological findings correspond well with regard to white matter lesions. PMID- 8446427 TI - Genetic defects in proteoglycan biosynthesis. AB - An overview on the structure of proteoglycans and on genetic defects in proteoglycan biosynthesis is given. Several patients with progeroid-like symptoms have been shown to have abnormalities in the biosynthesis of chondroitin/dermatan sulfate proteoglycans. A partial inactivity of galactosyltransferase I which catalyzes the second glycosyl transfer reaction in the assembly of glycosaminoglycan chains has been shown to represent the primary defect in one of the patients. A diminished concentration of a collagen-associated proteoglycan is considered to play a pathogenetic role in the development of loose skin. PMID- 8446428 TI - Diagnosis of peroxisomal disorders with neurological involvement. AB - Peroxisomal disorders are a group of inherited metabolic diseases caused by impairment of one or more peroxisomal functions. Ten disorders with neurological involvement have been recognized. Diagnosis and differentiation of these disorders is based on a number of important biochemical markers. For all disorders elevated values of very long chain fatty acids (VLCFA) and/or phytanic acid (PHYT) are important primary diagnostic parameters. Our results with regard to these two diagnostic markers are presented. VLCFA determined by gaschromatography in 414 samples (plasma, leukocytes or fibroblasts respectively) revealed increased values of hexacosanoic acid in 30 hemizygotes and 10 heterozygotes of adrenoleukodystrophy/adrenomyeloneuropathy and in eight infants with Zellweger disease or neonatal adrenoleukodystrophy. 15 cases with peroxisomal disorders were detected by VLCFA analysis in autopsy material. Gaschromatographic analysis of PHYT in plasma showed in some patients with Zellweger disease or neonatal adrenoleukodystrophy increase. In seven Refsum patients beside gaschromatographic demonstration of PHYT accumulation in plasma, analysis of plasma phytanyltriglycerides by thin-layer chromatography proved to be a rapid and reliable method for detection of patients and monitoring dietary treatment. PMID- 8446429 TI - Experience with the 3-phenylpropionic acid loading test for diagnosis of medium chain acyl-CoA dehydrogenase deficiency (MCADD). AB - MCADD is an autosomal recessively transmitted inborn error of C6-C12-carboxylic acid metabolism, causing episodically attacks of life threatening hypoketotic hypoglycemia or Reye-syndrome-like disease. Diagnosis is made best by investigating urinary organic acids before and after a load with 3 phenylpropionate. From 1986 until now 29 patients with MCADD were detected in Freiburg by selective screening for inherited metabolic disorders; 27 of them were confirmed by challenging with 3-phenylpropionic acid. The remaining two patients were not available for further investigations. The 3-phenylpropionate loading test is recommended in patients suffering from recurrent attacks of hypoketotic hypoglycemia and in families, where sudden infant death syndrome (SIDS) or near miss SIDS has occurred. PMID- 8446430 TI - Activity of nociceptive modulatory neurons in the rostral ventromedial medulla associated with volume expansion-induced antinociception. AB - A wide range of environmental stimuli have been shown to induce antinociception. Investigation of the brain regions contributing to environmentally induced antinociception (EIA) has focused primarily on the effect of disrupting neural transmission at various CNS sites. In contrast, the present study analyzed changes in the activity of nociceptive modulatory neurons in the rostral ventromedial medulla (RVM) following induction of antinociception by a physiological stimulus, volume expansion. Previous research indicates that 2 classes of RVM neuron, the on- and off-cells, facilitate and inhibit nociception, respectively. In the present study, volume expansion induced by intravenous administration of Ficoll inhibited the tail-flick reflex in 17 of 21 rats and simultaneously increased the firing rate of off-cells and decreased that of on cells. Changes in cell activity occurred only in those rats in which antinociception was produced. Lidocaine inactivation of the RVM did not block antinociception produced by Ficoll infusion. These findings demonstrate that, although antinociception produced by physiological activation of vagal afferents is associated with an increase in off-cell and a decrease in on-cell activity, these changes are not required for volume expansion-induced antinociception. PMID- 8446431 TI - Ethnocultural influences on variation in chronic pain perception. AB - In multiple studies cultural affiliation has been found to have an important influence on perception of and response to experimental and acute pain. Despite that evidence little work has been directed to understanding the cultural dimensions of the chronic pain experience. We present the results of a quantitative study of reported chronic pain perception in 372 chronic pain patients in six ethnic groups, who were under treatment at a multidisciplinary pain-management center. The role of ethnic and cultural experiences in the complex array of physical, cultural, psychological and social factors which influence the chronic pain experience is identified. Ethnocultural affiliation is important to chronic pain perception and response variation. In this study population the best predictors of pain intensity variation are ethnic group affiliation and locus of control (LOC) style (ethnic group identity is also a predictor of LOC style). It appears that pain intensity variation may be affected by differences in attitudes, beliefs and emotional and psychological states associated with the different ethnic groups. This study suggests a biocultural model may be useful in conceptualizing the complex interaction of biological, cultural and psychosocial factors in the process of human pain perception. Although it is likely that intense pain affects attitudes and emotions, it is also very likely that attitudes and emotions influence reported perceptions of pain intensity. Pain intensity variation in this study population is not significantly associated with diagnosis, present medication types, or types of past treatments or surgeries for pain. PMID- 8446432 TI - The distribution of brain-stem and spinal cord nuclei associated with different frequencies of electroacupuncture analgesia. AB - Immunocytochemical localization of the c-fos primary gene protein, Fos, was used to identify spinal cord and brain-stem sites activated by either 4-Hz or 100-Hz electroacupuncture (EA) applied to the Zusanli acupuncture points of both hind limbs in lightly anesthetized Sprague-Dawley rats. The number and distribution of Fos-immunoreactive neurons in the brain stem and spinal cord of 4-Hz and 100-Hz EA-treated rats were compared with these in anesthesia and room control rats. Compared to non-stimulated control rats or rats in which EA was applied to a non acupuncture point, both 4-Hz and 100-Hz EA-treated groups exhibited a significantly greater number of Fos-labeled neurons in the dorsal horn of the L2 spinal cord segment, lateral parabrachial nucleus, substantia nigra, nucleus raphe pallidus, dorsal raphe, locus coeruleus, posterior pretectal nucleus, and the lateroventral periaqueductal gray. In the 4-Hz-treated group, significant increases in Fos labeling were also observed in the cuneiform nucleus, dorsal and laterodorsal subdivisions of the periaqueductal gray, habenular nucleus, arcuate hypothalamic nucleus, and the lateroventral and lateral hypothalamic nuclei as compared to non-stimulated controls. The only brain-stem nucleus that exhibited significantly increased Fos-immunoreactive neurons in 100-Hz but not 4-Hz EA was the rostolateroventral nucleus of the medulla. These results indicate that many brain-stem regions are activated by both 4-Hz and 100-Hz EA but additional brain stem regions are selectively activated by 4-Hz EA which may relate to the opiate sensitivity of 4-Hz EA. In sum, these data identify several distinct brain-stem nuclei that may play a role in acupuncture-mediated analgesia. PMID- 8446433 TI - Evaluation of a chronic pain programme by referring physicians. AB - A neglected source of treatment outcome evaluation is the opinion of the referring physicians. We report on 179 patients with chronic pain who were admitted to a 6 week inpatient inter-disciplinary pain programme. A retrospective 2 page mail questionnaire accompanied by initial letters of referral was sent to the referring physicians. We hypothesized that the main reason family physicians referred patients was to establish a management plan. The physician response rate was 70%, encompassing 72% of the patients. Intra-observer reliability was tested by a second mailing 3 months later (68% response rate). Test-retest reliability, and correlations between questions were significant and are reported for: reasons for referral, the utility of the discharge summary, coping, and behavioural changes at discharge and at time of the questionnaire. This appears to be the first report of a survey of the evaluation of a pain programme by referring physicians. PMID- 8446434 TI - Effects of morphine and naloxone on basal and evoked Fos-like immunoreactivity in lumbar spinal cord neurons of arthritic rats. AB - We have previously shown, on the one hand, that the number of Fos-like immunoreactive (Fos-LI) neurons in the lumbar spinal cord observed during the development of adjuvant-induced arthritis in the rat correlates with the clinical and behavioral scores and, on the other hand, that the number of Fos-LI neurons induced by repeated mechanical pressure to the ankle was greater in arthritic animals than in healthy ones. In non-stimulated arthritic rats, Fos-LI neurons were mainly present in the neck of the dorsal horn and in the ventral horn of L3 L5, whereas following stimulation they were numerous in the superficial laminae. The aim of this study was to evaluate Fos-LI following morphine injection (1) in arthritic animals in the absence of any stimulation, (2) in arthritic rats after ankle stimulation pretreated with morphine or by the combination of morphine and naloxone, and (3) following naloxone treatment in non-stimulated and stimulated polyarthritic rats. In non-stimulated arthritic rats, a single morphine injection (1-9 mg/kg, i.v.) or a single naloxone injection (1-3 mg/kg, i.v.) induced no change in the basal Fos-LI present in lumbar spinal neurons. In contrast, Fos-LI evoked by noxious pressure was strongly depressed by morphine. In the superficial laminae pretreatment with a single morphine injection of either 0.5 or 1 mg/kg, i.v., reduced by more than 50% the number of Fos-LI neurons and at 3 mg/kg completely abolished the labeling evoked by the stimulation. Similar effects were obtained in the neck of the dorsal horn. These effects were reversed by naloxone (morphine 3 mg/kg and naloxone 0.3 mg/kg). Pretreatment with naloxone (1 mg/kg) did not change Fos labeling. This study which is based on mechanical stimulation in arthritic rats confirms and extends previous investigations and demonstrates that the use of Fos-LI is a suitable method to reveal the efficacy of opioid analgesic. However, the lack of effects of opioids on basal labeling suggests that long-term drug treatment should be used to study the effects of various putative analgesics on chronic pain models. PMID- 8446435 TI - Effects and side effects of a percutaneous thermal lesion of the dorsal root ganglion in patients with cervical pain syndrome. AB - Twenty consecutive patients with intractable chronic pain in the cervical region were treated with a radiofrequency lesion of the dorsal root ganglion on level C4, C5 or C6. Electromyography (EMG) and sensory evoked potentials (SEP) were recorded before and 3 weeks after the radiofrequency lesion. Side effects were studied 3 weeks, 6 weeks and 3 months after the procedure. Pain scores were evaluated on Numeric Rating Scales (NRS) before and 6 weeks after treatment. The patient was interviewed 3, 6 and 9 months after the radiofrequency lesion. The most common side effect was burning pain in the dermatome of the treated nerve root. Hyposensibility in the dermatome was noticed in 35% of patients. Except in 1 patient, these side effects had disappeared 6 weeks after treatment. The EMG showed no signs of denervation. One SEP recording remained abnormal after treatment. There was initial pain relief in 75% of patients after 3 months and in 50% of the patients after 6 months. In conclusion, this study did not reveal any signs of motor denervation after a percutaneous partial rhizotomy. There were no long-term signs of deafferentation. Initial pain relief was found in 75% of patients, but there was a marked tendency for pain to recur in a period from 3 to 9 months after treatment. PMID- 8446436 TI - Spinal cord stimulation in failed back surgery syndrome. AB - We have reviewed our experience with spinal cord stimulation in treating patients with the failed back surgery syndrome and have assessed patient and patient selection characteristics as predictors of the long-term outcome. Neuroradiological investigations eliminated the possibility of a surgically treatable lesion and electromyogram assessed the chronic radicular suffering in correlation with the complaints and the clinical examination of the patient. Excellent pain relief (75% or more) during 1 week of trial stimulation and no major psychiatric or psychological pathology were criteria of selection. Seventy eight patients underwent trial stimulation. Fourteen (18%) failed to obtain excellent pain relief during 1 week of stimulation and their electrodes were removed. The remaining 64 underwent an internalization of the system and they were followed by a clinical observation every 3 months and this for a mean follow up period of 4 years (range: 1-7 years). Thirty-five patients (55%) continued to experience at least 50% of pain relief at the latest follow-up. Fifty-eight patients (90%) were able to reduce their medication, 39 patients (61%) reported a change in lifestyle, in that their ability to perform daily activities had improved significantly. Fifty-three patients (83%) continued to use their device at the latest follow-up. PMID- 8446437 TI - The effect of low-level laser therapy on musculoskeletal pain: a meta-analysis. AB - A meta-analysis was undertaken of low-level laser therapy (LLLT) on musculoskeletal pain. A literature search revealed 23 LLLT trials and of these 17 were controlled trials. Ten were double blind and 7 were insufficiently blinded. Within the studies identified pain was assessed by visual analogue scale or by "some other indices of pain". Nine double-blind trials and 4 controlled trials presented results in a form which allowed pooling of data. In the double-blind trials, the mean difference in pain between LLLT and placebo was 0.3% (S.E.(d) 4.6%, confidence limits -10.3-10.9%). In the insufficiently blinded trials the mean difference in pain was 9.5% (S.E.(d) 4.5%, confidence limits -2.9-21.8%). We conclude that LLLT has no effect on pain in musculoskeletal syndromes. PMID- 8446438 TI - Perineal pain after rectal amputation: a 5-year follow-up. AB - A long-term study was undertaken on 286 patients who underwent perineal resection for rectal cancer to ascertain the incidence of chronic post-surgical pain in this group and to determine the likely cause for these pains. In 33 patients (11.5%) experiencing persistent perineal pain over the 5-year follow-up, most (70%) developed pain within weeks after surgery. The remaining 30% presented with pain several months later. This group with late onset pain died from known recurrence of adenocarcinoma in 80% of cases, giving this symptom the highest early confirmatory sign for tumour over other clinical tests. Those with early onset pain had a 26% tumour recurrence rate and clinical features of pain indicative of phantom anorectal pains in most cases. While the pain-onset time from surgery was the most sensitive predictor of cause and outcome, other distinguishing features in respect of site and quality of pain as well as differing responsiveness to drug therapy allowed for further separation of deafferentation from nociceptive pain for these two clinical groups. PMID- 8446439 TI - The pain of heel prick and its measurement in preterm infants. AB - Variability of physiological parameters was used as a measure of stress in the newborn infant. There was a significant increase in variability of the heart rate (P < 0.01) when the stab of the heel prick occurred in addition to the other elements of the procedure (positioning, warming, alcohol swab cleansing and squeezing). This dummy procedure itself caused some increase in variability although this was not significant at the 5% level. There were similar significant increases in variability of the respiratory rate and O2 and CO2 tensions in the blood (P < 0.05) during the stab procedure. PMID- 8446440 TI - Quantitative sensory examination during epidural anaesthesia and analgesia in man: effects of morphine. AB - In a double-blind placebo-controlled cross-over study the effects of epidural morphine (4 mg) on somatosensory functions were investigated in 10 healthy volunteers. Detection, pain detection and pain tolerance thresholds to thermal, mechanical and electrical stimuli as well as magnitude rating of short-lasting stimuli of the same modalities were monitored before and for 10 h after epidural administration of 4 mg of morphine or saline. Epidural morphine induced a naloxone-reversible (0.1 mg/kg, i.v.) increase in pain detection threshold to heat and mechanical stimuli and in pain tolerance threshold to heat, mechanical and electrical stimuli. Morphine induced a more pronounced increase in the pain tolerance than in the pain detection threshold. Magnitude rating of short-lasting radiant heat (argon laser) stimuli were reduced by epidural morphine in comparison to placebo while there was no significant difference between the effects of morphine and placebo on magnitude rating of short-lasting mechanical and electrical stimuli. The warm detection threshold was increased (naloxone reversible) by morphine. Segmental distribution of pruritus was reported by 7 subjects following epidural morphine which was replaced by a short-lasting burning sensation following naloxone administration. Naloxone (0.1 mg/kg) preceeded by placebo did not change somatosensory functions. These results indicate that the somatosensory effect of epidural morphine is dependent on the types of afferent fibres activated as well as on the duration and intensity of the stimulus. PMID- 8446441 TI - Enhancement of morphine analgesia by fenfluramine in subjects receiving tailored opioid infusions. AB - We evaluated the ability of fenfluramine, a serotonin releaser, to increase the analgesic potency of morphine administered by tailored i.v. infusion. Ten normal volunteers participated in 4 test sessions, involving different treatments on different days: (1) oral placebo/saline infusion, (2) oral placebo/morphine infusion, (3) oral fenfluramine (60 mg)/saline infusion, and (4) oral fenfluramine/morphine infusion. Subjects experienced repetitive painful dental electrical stimuli at strong but tolerable intensities during testing. On the 2 test days involving morphine, the opioid was administered by a computer-pump system that used individual pharmacokinetic parameters to achieve consecutive, steady plasma concentrations near target values of 16, 32 and 64 ng morphine/ml; each morphine concentration plateau was maintained for 45 min. On the saline infusion days, our procedures were identical to morphine test days except that the infused fluid contained no drug. For all sessions outcome measures included subject ratings of pain intensity, dental evoked potential (EP) amplitude, and visual analog scale (VAS) ratings of subjective side-effect intensities (nausea, alertness, dizziness, itching, mood). We obtained these measures during baseline and at each morphine concentration plateau or at corresponding times during saline infusions. Fenfluramine significantly increased the analgesic potency of morphine during the opioid infusion, while fenfluramine alone produced borderline analgesic effects. Fenfluramine alone decreased alertness slightly, but did not significantly increase morphine side effects. Thus, we conclude that fenfluramine enhances the analgesic potency of morphine without a parallel increase in opioid side-effect potency. PMID- 8446442 TI - Regional intracoronary analgesia during percutaneous transluminal coronary angioplasty. AB - The ischemic pain associated with balloon inflation during coronary angioplasty remains a significant source of procedural discomfort and sets a limit on the duration of percutaneous transluminal intravascular interventions. The present study examined whether intracoronary lidocaine reduced the pain of coronary angioplasty. Sixteen patients undergoing elective coronary angioplasty underwent three 90 sec balloon inflations: the first with administration of no intracoronary agent, and the second and third with administration of one or the other of placebo or an equal volume of lidocaine (10-16 mg). Placebo or lidocaine were randomized in administration sequence and were given just before balloon inflation. During the occlusions, pain was scored on an ordinal scale (0 = no pain; 10 = most severe pain). Lidocaine delayed the onset of pain (23 +/- 4 vs. 48 +/- 7 sec, P < 0.005) and reduced its magnitude (at end-inflation: 7.8 +/- 1.3 vs. 3.2 +/- 1.3, P < 0.01). There were no significant hemodynamic or electrophysiologic effects in this group of patients, although atrioventricular conduction was delayed when lidocaine was administered into the epicardial coronary which had the atrioventricular node artery as a branch. Intracoronary analgesia with lidocaine is safe and effective in a select group of patients with normal ventricular function undergoing elective coronary angioplasty. PMID- 8446443 TI - Skin potential recordings during cystometry in spinal cord injured patients. AB - In order to investigate autonomic mechanisms associated with bladder filling and bladder contraction, skin potentials from the hands and the feet of 32 spinal cord injured patients were recorded during cystometry. All had a complete clinical loss of motor and sensory function below the lesion, but in 3 patients, the autonomic lesion was electrophysiologically assessed as incomplete. In patients with a complete autonomic lesion, any rise in intravesical pressure associated with bladder hyperreflexia induced SP responses below the level of the lesion. SP responses were never obtained during bladder filling, as the intravesical pressure remained low. These results tend to confirm those of Guttmann and Whitteridge, but differ in so far as SP responses at the foot were a regular finding in all paraplegic and in most tetraplegic patients. Furthermore, bladder contraction failed to elicit SP responses below the level of the lesion in patients with an incomplete autonomic lesion. This study emphasises the importance of assessing the integrity of the autonomic nervous pathways when dealing with autonomic mechanisms in spinal cord injured patients. The possible relation between SP responses and bladder neck dysfunction is further discussed. PMID- 8446444 TI - The chances of a spina bifida patient becoming continent/socially dry by conservative therapy. AB - One hundred and one patients with neurogenic lower urinary tract dysfunction due to myelomeningocele or sacral dysplasia, all older than 10 years of age, with a mean age of 15 years, and under regular urological control for many years were evaluated to discover if they had achieved urinary continence (dry day and night) or the status of socially dry (with dry intervals of more than 3 hours) with conservative means of treatment; or whether they remained incontinent or required operative procedures. The results were correlated with the urodynamic pattern of their detrusor-sphincter dysfunction and with the methods they used for bladder emptying. Special attention was paid to the effects of the various conservative treatment modalities nowadays available. The chances of becoming continent or at least socially dry by conservative therapy are best for patients with sphincter hyperreflexia provided that (1) the detrusor was already hypo- or areflexic, or detrusor hyperreflexia could be successfully controlled, and (2) that regular bladder emptying was achieved by clean intermittent (self) catheterisation. Twenty-four out of 45 patients in this group fulfilled these criteria: 18 are continent, 6 socially dry, a success rate of 54%. In patients with sphincter weakness the outlook is worse: in combination with detrusor hyperreflexia there is only a 16% chance, and in those with detrusor areflexia a 37% chance of becoming continent or socially dry, with the best results in wheelchair patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446445 TI - Ambulation in patients with myelomeningocele: a study of 1500 patients. AB - Data from 1500 patients affected by spina bifida have been collected in a multicentre study in Spain from 1986 to 1988. This paper is concerned with a part of the data, specifically regarding the walking of patients and certain factors that influence the prognosis for ambulation. The neurological level of lesion most commonly present was lumbosacral (65.6%). Hydrocephalus was frequent (62% of the sample), and has significant implications regarding prognosis for walking. Hip dislocation (32%) and scoliosis (22.9%) were orthopaedic problems noted in our sample. Pressure sores appeared in 31.7% of the patients. The onset of walking ability has been studied; 15% of the sample started walking at an age older than 5 years. Finally, different modalities of ambulation are described according to the use of ancillary devices, and in independence in activities of daily living. PMID- 8446446 TI - Length-tension relationship of the posterior deltoid to triceps transfer in C6 tetraplegic patients. AB - We assessed the length-tension relationship of the posterior deltoid to triceps transfer in 8 tetraplegics (n = 11 transfers) and compared the results to the length-tension relationship of the normal triceps measured in a check sample composed of 9 able bodied, right handed women. We designed a device to lock the arm and forearm and used a force transducer to assess the torque output isometrically. The muscle was tested at 6 different lengths (130, 110, 90, 70, 45 and 0 degree of elbow flexion) with the shoulder abducted at 90 degrees. As expected, the transfer behaved differently from the normal triceps. The mean maximum torque recorded was 7.8 Nm in patients while it was 27 Nm in the check sample. When compared, the absolute values (ie values expressed with a dimension of torque) were significantly different between groups (0.00001 < p < 0.002). The expression of this relation (ie the relative values expressed as percentage of maximum values) revealed significant statistical differences (p < 0.002) at 90 and 70 degrees of elbow flexion; the peak torque was recorded at 130 degrees in patients while it was recorded at 110 degrees in the check sample, with a plateau between 110 degrees and 70 degrees. On the other hand, if the length-tension relationship was fairly similar among subjects of the check sample, it exhibited tremendous differences among patients; it seemed that initial tension given by the surgeon represented a variable difficult to control without a device dedicated to that task. PMID- 8446447 TI - Sonographic diagnosis of heterotopic bone formation in spinal injury patients. AB - A variety of stimuli including neurological insult may provoke primitive mesenchymal cells to differentiate into bone forming cells. Such a sequel following spinal cord injury can delay rehabilitation, enhance the spasticity and reduce the range of movement in the affected joint. It is characterised by an initial inflammatory phase followed by heterotopic bone formation. The early inflammatory lesion clinically mimics deep vein thrombosis, a developing pressure sore, infection, and tumour. An early diagnosis at a time of clinical uncertainty, before the plain radiographic features develop, has distinct advantages and therapeutic implications. The unique pathological evolution and maturation of the lesion is clearly demonstrated by sequential sonographic (ultrasonic) assessment with depiction of the 'zone phenomena' seen on histology. Sonographic scans in 7 spinal injury patients proved diagnostic, before there was radiographic evidence of bone formation, and confidently excluded HBF in a further 18 patients without any false negative results. PMID- 8446448 TI - Neurovascular complications of heterotopic ossification following spinal cord injury. AB - Compression of neurovascular structures from heterotopic ossification can result in neurological and vascular sequelae. Three cases of neurovascular compression due to heterotopic ossification illustrate the potential for neurovascular compression resulting from this condition and underscore the importance of recognising this uncommon, but notable complication following spinal cord injury. PMID- 8446449 TI - Conservative treatment of burst fractures of the thoracolumbar and lumbar spine. AB - Twenty-three patients with burst fracture of the thoracolumbar and lumbar spine were treated nonoperatively. Among these 23 patients, 13 had a neurological deficit and 10 patients did not have such a deficit. Union of burst fractures occurred with conservative treatment in 22 out of 23 patients, but late operation was necessary in only one patient, who had an increasing kyphotic deformation. Of the 13 patients with neurological deficit, 8 showed full recovery and none had neurological deterioration. It was observed by CT scans that the narrowing of the spinal canals was progressively relieved by natural remodelling of the fragments retropulsed into the spinal canal. PMID- 8446450 TI - Spinal cord injuries in Iceland 1973-1989. A follow up study. AB - All traumatic SCI patients in Iceland come to the Neurosurgical Department of Borgarspitalinn, the City Hospital in Reykjavik for their initial treatment. From 1973-1989, 79 (93%) were rehabilitated at Borgarspitalinn. The purpose of this study was to look at the most common complications and the social functions of SCI patients after discharge from the Rehabilitation Department. A questionnaire was sent to 59 of the 79 patients. They represent almost the whole population of the spinal cord injured population in Iceland. Forty-five patients (76.3%) answered the questionnaire, 69% male, 31% female. Sixty-seven percent were under the age of 30 years at the time of injury. Twenty-nine percent had a complete spinal cord injury; 53.3% were wheelchairbound (Frankel grade A, B, C); 55.6% were quadriplegic, and 44.4% paraplegic. The commonest complications were pain (64.4%), urinary tract infections (62.2%) and spasticity (60%); and 58% of the wheelchairbound patients had had pressure sores. Fifty-five point five percent were married; 71% had an active sexual life after the injury; 54% of the wheelchairbound patients were not quite independent and required some assistance with activities of daily living (ADL) tasks; and 29% were not working or studying compared to 11%, who were, before the injury. No significant changes were seen in social function after the injury. The results show that more emphasis must be placed on the prevention of complications such as urinary tract infections and pressure sores and on the treatment of chronic pain and spasticity. PMID- 8446451 TI - Surgery for progressive Pott's paraplegia (tuberculous paraplegia) PMID- 8446452 TI - The lack of comprehensive care causing complications in patients with myelodysplasia. AB - In recent years those working in German SCI centres have realised that a growing number of young adults with myelodysplasia are seeking special treatment because of the lack of comprehensive and lifelong care. Statistical investigations, collected over a period of nine years, demonstrate that only severe complications in soft tissues, urology and equipment have led to an admission. The capacity of the centres is limited, and more facilities are necessary. There is a political demand. PMID- 8446453 TI - 28 K in squamous metaplasia of the bladder in patients with spinal cord injury. AB - Antibody to 28 K was used to examine sections of bladder biopsies obtained by cystoscopy from 14 patients with spinal cord injury (SCI). Most of the biopsies were obtained from patients with indwelling catheters during the investigation for possible malignancy. Sections of bladder were stained by the streptavidin procedure. The 28 K in the normal transitional epithelium of the bladder was in the superficial cells (umbrella cells). All the biopsies from patients with indwelling urethral catheters showed areas of squamous metaplasia usually associated with evidence of chronic inflammation. Cystitis cystica glandularis was also seen in one patient. Staining was most marked in the areas of squamous metaplasia with intracellular granular staining. The basal layers were not well stained. With marked squamous metaplasia, there was a superficial hyperkeratotic layer that stained variably and often did not stain at all. Staining was less marked in areas of hyperplasia, regenerating urothelium, and cystitis cystica glandularis. These findings raise the possibility that the presence of 28 K glycoprotein in the tissues or released into the urine may be used as an indicator of squamous metaplasia and chronic inflammation of the bladder. PMID- 8446454 TI - The physiological benefits of paraplegic orthotically aided walking. AB - A group of first-time paraplegic users of a particular ambulatory orthosis was studied to assess the physiological benefits of changing from a wholly sedentary lifestyle to one which included regular periods of upright weight-bearing and walking. Little clinically apparent benefit was noted in respiratory mechanics. There was a subjective reduction in urinary tract infections, but without a corresponding reduction in the level of bacteria. A possible improvement in bone density was noted in a small subgroup. It is concluded that, at least in the shorter term, the physiological benefits to paraplegics of using walking orthoses are not as great as has generally been claimed in the literature. PMID- 8446455 TI - A new double-purpose device for elbow extension in tetraplegia with paralysis below C5. AB - A new device for elbow extension, developed as a dynamic orthosis and also as a static splint for a C5 tetraplegic arm, is presented. A patient with tetraplegia, probably related to infection of the central and peripheral nervous system, had a paralysed right triceps muscle, with a very strong corresponding biceps. Extension by force of a posterior stretched rubber ring made the arm useful, while the possibility to lock the elbow hinges of the orthosis at any desired angle enabled static splinting of the elbow to increase the range of motion. PMID- 8446456 TI - A complicated trochanteric pressure sore: what is the best surgical management? Case report. AB - Pressure sores are a common complication after spinal cord injury. But great advances in their management (nursing care, prevention and surgery) have been made in the last four decades. Neglected pressure ulcers may affect the adjacent joint, leading to septic arthritis. We report a paraplegic patient with a large trochanteric sore with hip arthritis, in whom we performed an upper femoral resection and acetabular curettage (Girdlestone's technique) and coverage with the homolateral vastus lateralis muscle flap in one stage. Some questions pertaining to this operation are discussed and there is a comparison with other ways of management described in the literature. We conclude that a successful outcome with the management of such large sores depends on a radical, aggressive operation to remove all of the affected tissue, and ensure a safe coverage with a reliable, viable muscle flap. The collaboration and the positive attitude of the patient towards the procedure and the result obtained are decisive in preventing recurrences. PMID- 8446457 TI - Effects of cisapride on anorectal and vesicourethral function in spinal cord injured patients. AB - The effect of cisapride on constipation in para and tetraplegia is well known. We have investigated the effects of this prokinetic drug on anorectal activity and on the function of the lower urinary tract. One result of the anorectal study showed a significant increase in activity and a reduction in compliance of the ampulla. The urodynamic study demonstrated earlier and higher amplitude reflex contractions in hyperactive bladders; hypoactive bladders significantly reduced their compliance. No functional alterations of striated urethral sphincter were observed. PMID- 8446458 TI - Spinal cysticercosis. Case report and review. AB - Cysticercosis is the commonest parasitic disease to affect the central nervous system (CNS). According to the World Health Organisation (1988), more than 2.5 million people worldwide are infected. Neurocysticercosis (NCC) is caused by the encysted larval form (porcine tapeworm) of Taenia solium (Cysticerus cellulosae). The ways in which the eggs of T Solium penetrate the CNS are illustrated in Table I. Involvement of the spinal cord in NCC varies between 1% and 5%. The isolated medullary form is very rare, only 50 cases having been reported up to 1988. The appearance of a spinal cord compression syndrome (SCCS) is unusual and late, according to reported series, the largest being that of Sotelo with 753 cases of NCC, including 10 causing SCCS, corresponding to 1.4%; also the classic Dixon and Lipscomb series of 450 NCC with only one patient with SCCS. PMID- 8446459 TI - Late-onset papilledema following spinal injury. Case report. AB - Papilledema, is a known complication of various spinal pathologies. It has, however, been only infrequently reported following spinal injury, and may be overlooked in these cases. Presented herein is a 27 year old male who suffered thoracic and lumbar spinal injuries. Papilledema following mild increase in intracranial pressure (IICP) developed 3 weeks following trauma, and subsided within 8 weeks. The importance of routine repeat ophthalmoscopic examinations following spinal injury to detect changes characteristic of IICP is emphasized. PMID- 8446460 TI - A review of some measurements of muscle wasting, tone and clonus in paraplegia. PMID- 8446461 TI - Rehabilitation of spinal cord injured patients on long term ventilation. AB - Recent advances in roadside management and resuscitation techniques have resulted in an increased survival rate of people with high cervical cord injury. A few become partially or permanently ventilator dependent. Not only are these people dependent on assisted ventilation, but their speech is also compromised, along with loss of voluntary control and many other bodily functions, as they are tetraplegic. By using recent technological advancements, such as portable ventilators, phrenic nerve stimulation, environmental controls and specialised wheelchairs it has been possible to manage such patients at home. Furthermore, patients on ventilators are unable to have verbal communication. There is therefore a need for them to develop either augmentative communication or the use of alternative communication aids. Recent published reports indicate the factors other than the clinical state that may prevent such patients from taking advantage of modern advances; the main issues appear to be cost factors, community care provision and ethical considerations. PMID- 8446462 TI - The impact of home based ventilator dependence on family life. AB - Those who experience spinal trauma above the level of C4 require continued ventilation to keep them alive. Over the past 15 years considerable expertise has been developed in not only successfully treating these patients, but also returning them to their home environment with full ventilator support. Little objective evidence is available concerning the views of those who receive permanent ventilation and whether they or their relatives consider it would have been better to allow them to die. The present investigation examined the perceived value of returning home whilst still requiring ventilation, from the point of view of both the injured persons themselves and their nearest relatives. Objective analyses were made using the Family Environment Scale (Moos 1986) and a measure of affective state of the interaction patterns within each of the families. Although there was some alteration in affective state experienced in most families, the most important factors associated with adaptation appear to be the level of communication within the family and the degree of commitment between all family members. PMID- 8446463 TI - Antibody responses to invariant antigens of Trypanosoma congolense in cattle of differing susceptibility to trypanosomiasis. AB - Five trypanotolerant N'Dama (Bos taurus) and five susceptible Boran (Bos indicus) cattle were challenged by tsetse flies infected with Trypanosoma congolense IL 13 E3. These animals had experienced five previous infections with T. congolense, each terminated by drug therapy. Immunoblotting and ELISA were used to determine isotype and specificity of antibody responses to trypanosome invariant antigens. Both IgM and IgG1 were elicited, but the IgG1 responses were directed against a greater diversity of antigens. A 69 kD antigen was the major invariant antigen which elicited IgM antibodies in both breeds, but the N'Damas also responded with high levels of specific IgG1. Analysis of isotypic responses to whole trypanosome extract also revealed lower levels of IgG1 and higher levels of IgM in the Borans than in the N'Damas, suggesting that a dysfunction in the switch from IgM to IgG might occur in infected Boran cattle. A 33 kD antigen appeared to elicit only IgG1. Sera from all five N'Damas and the two Borans which were most resistant to the disease reacted with this antigen prior to and following re-infection. Furthermore, during the primary T. congolense infection in the same animals, anti 33 kD antibodies were detectable in all five trypanotolerant N'Damas, but in none of the five susceptible Borans. Thus, the presence of antibodies to the 33 kD antigen of T. congolense appeared to be associated with a capacity to control the disease. PMID- 8446464 TI - The 35/50 kDa surface antigen of Trypanosoma cruzi metacyclic trypomastigotes, an adhesion molecule involved in host cell invasion. AB - We have previously shown that monoclonal antibodies directed to the 90 kDa glycoprotein and the 35/50 kDa glycoconjugate, present on the surface of Trypanosoma cruzi metacyclic trypomastigotes, inhibited host cell invasion. Here we investigated whether these molecules could be the ligands for the target cell receptor. Binding assays were performed by incubating Vero cells with sonicated parasite extract. Detection of bound parasite components was carried out by using monoclonal antibodies (MoAbs) IG7 and 10D8, which recognize the 90 kDa and the 35/50 kDa antigens respectively. These experiments revealed that the 35/50 kDa glycoconjugate of metacyclic forms, but not the 1G7-reactive antigen, binds to Vero cells. The purified 35/50 kDa antigen bound to Vero cells and inhibited the entry of metacyclic forms in a dose-dependent manner. Although to a lesser extent, an immunologically related 35/50 kDa antigen of non-infective epimastigotes also bound to Vero cells but it was unable to inhibit parasite penetration at a concentration (100 micrograms/ml) in which metacyclic antigen exhibited more than 60% inhibition. All these data suggest that the metacyclic 35/50 kDa surface glycoconjugate is a ligand to the host cell in the process of T. cruzi invasion. PMID- 8446465 TI - Isotype-specific antibody responses to Haemonchus contortus in genetically resistant sheep. AB - The kinetics of anti-Haemonchus antibody responses in serum and faecal extracts of pasture-reared, genetically resistant and random-bred sheep infected with Haemonchus contortus were examined using an isotype-specific ELISA. Anti Haemonchus antibodies of IgA, IgG1, IgG2 and IgM isotypes were detected in serum and faecal extracts of both resistant and random-bred sheep after challenge infection. Serum IgG1 and IgA levels in resistant sheep were significantly higher than in random-bred sheep between 10 and 31 days after infection. However, there were no differences in IgG2 and IgM antibody responses between the two genotypes. Faecal antibody responses to H. contortus showed a clear genetic effect with resistant sheep exhibiting higher IgA levels throughout infection and higher IgG1 levels between 24 and 31 days after infection. Furthermore, serum IgG1 and IgA, and faecal IgA responses were negatively correlated with faecal egg counts in both genotypes on 17, 24 and 31 days after infection. Together, these results are taken to indicate that anti-parasite IgA and IgG1 antibodies may play an important role in genetically determined resistance of sheep to haemonchosis. PMID- 8446466 TI - Characterization of allergens of the cat flea, Ctenocephalides felis: detection and frequency of IgE antibodies in canine sera. AB - Flea allergens, fractionated by polyacrylamide gel electrophoresis and transferred to nitrocellulose, were identified using 20 flea-allergic dog sera in an enhanced chemiluminescent assay for canine IgE antibodies. At least 15 different flea components in the molecular weight range of 14-150 K bound IgE and every serum demonstrated a different pattern of binding. Three of the components with apparent molecular weights of 25, 40 and 58 K were each bound by at least 40% of the sera. No reactivity was seen when normal dog sera were used. These results demonstrate a greater number of flea allergens and a far greater diversity of the IgE antibody response to flea allergens than has previously been described, and suggest that immediate hypersensitivity may be an important mechanism in the pathogenesis of canine flea allergy. PMID- 8446467 TI - Vaccine development against cutaneous leishmaniasis. Subcutaneous administration of radioattenuated parasites protects CBA mice against virulent Leishmania major challenge. AB - Experiments described in this paper were aimed at determining whether subcutaneous inoculation of live, avirulent Leishmania major would protect mice against infection by the virulent parasite. To this effect, promastigotes or amastigotes of a highly virulent strain of L. major (MRHO/IR/76), used in human trials of leishmanization, and which induces non-healing skin lesions in both CBA and BALB/c mice, were rendered non-pathogenic by gamma irradiation. A dose of 150 krad was required to abrogate the virulence of the parasite as tested on BALB/c mice. Strikingly, however, not all leishmanias were completely inactivated by this procedure since live parasites were detected in the footpads and/or the inguinal lymph nodes as long as 28 days (CBA) or 18 weeks (BALB/c) after injection. Furthermore, 150 krad-irradiated promastigotes retained the capacity to transform into amastigotes intracellularly in vitro. Subcutaneous inoculation of this irradiated 'vaccine' conferred onto CBA mice a high degree of protection against challenge by both the homologous and a heterologous (MRHO/SU/59/P) strains of L. major. Lymph node cells from protected animals acquired the capacity to activate infected macrophages in vitro to kill intracellular L. major. To allow for maximum development of immunoprotection, the irradiated promastigotes had to remain viable, perhaps reflecting a requirement for transformation into amastigotes in the vaccinated host. PMID- 8446468 TI - Transcripts of the multidrug resistance genes in chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum. AB - Homologues of the mammalian multidrug resistance gene have been identified in isolates and clones of Plasmodium falciparum and designated pfmdr1 and pfmdr2. Mutations in pfmdr1 have been associated with chloroquine resistance but confirmation could not be obtained in a genetic cross. We have examined the copy number and expression of pfmdr1 and pfmdr2 in chloroquine-sensitive and resistant P. falciparum and have found no relationship between the copy number of either gene and chloroquine resistance. However, a marked correlation was seen between levels of mRNA transcribed for each gene and chloroquine resistance. Two transcripts of pfmdr1 were detected, and in the asexual blood cycle an 8 kb transcript appeared first, followed by the appearance of a 7 kb species. PMID- 8446469 TI - Effects of irradiation on surface carbohydrates of larvae of Schistosoma mansoni. AB - Ultra-violet irradiated larvae of Schistosoma mansoni stimulate high levels of resistance to challenge infection in experimental animals. In the experiments presented here, the binding patterns of antisera specific for the cercarial glycocalyx, and of various lectins, demonstrate that u.v. irradiation causes a pronounced modification of the carbohydrate antigens expressed at the surface of cercariae and newly transformed schistosomula. These alterations were dependent on the irradiation dose, and on the batch of cercariae used in each experiment. Our results strongly suggest that the changes in carbohydrate antigens consequent upon u.v. irradiation may be important in generating the enhanced immunogenicity of irradiated cercariae. PMID- 8446470 TI - Purification of an agglutinin from the haemolymph of the snail Bulinus nasutus and demonstration of related proteins in other Bulinus spp. AB - The snail Bulinus nasutus 1214 possesses a potent haemagglutinin (end-point titre with human erythrocytes, 2(-18)) in its cell-free haemolymph which also binds to the miracidia (but not other larvae) of the incompatible parasite Schistosoma margrebowiei. We have purified a protein possessing this haemagglutinating property from the plasma of this snail. The native Mr of this protein was estimated by SDS polyacrylamide gel electrophoresis to be 210 kDa; under denaturing conditions in a 7.5% PAGE gel it ran as a major band of 135 kDa. Proteins of similar Mr were also found in the haemolymph of 16 other Bulinus spp. (the major intermediate hosts of human and veterinary schistosomiasis in Africa) although the plasma of none of these agglutinated human erythrocytes. Nonetheless, Cleveland mapping of the Mr 135 kDa bands from these different Bulinus spp. revealed 4 identical major peptide fragments (30, 28, 19 and 16 kDa) in each, thus demonstrating a similarity in the primary structure of these plasma proteins. Antisera from Balb/C mice immunized with the 135 kDa polypeptide from Bulinus truncatus 1521 cross-reacted in Western blots with the 135 kDa band of other members of the same truncatus/tropicus species complex but not with species from the africanus or forskalii species groups. PMID- 8446471 TI - Observations on the feeding behaviour of parasitic third-stage hookworm larvae. AB - The feeding behaviour of parasitic 3rd-stage larvae (L3) of the hookworms Ancylostoma caninum, A. ceylanicum and Necator americanus was examined. Less than 11% of A. caninum L3 recovered from the small intestines of dogs infected orally were feeding at 4-48 h post-infection (p.i.), and none of the A. ceylanicum L3 recovered from the intestines of orally infected hamsters had resumed feeding. All L4 of both species recovered at 36 and 48 h p.i. had resumed feeding. On the other hand, approximately 16% of the A. ceylanicum L3 recovered from the skin of percutaneously infected hamsters at 18 h were feeding, and the percentage feeding increased to nearly 58% at 44 h p.i. Necator americanus L3 recovered from the skin of percutaneously infected neonatal hamsters resumed feeding at 6-12 h p.i. and reached 90-94% by 18 h. Feeding began to decline at 66 h, and reached 29% at 120 h p.i. This decrease was associated with the migration of larvae from the skin to the lungs. By 192 h p.i. over 95% of the larvae had reached the small intestine, and all had moulted to the L4. The results indicate that parasitic L3 resume feeding in the skin during percutaneous infections, and suggest that feeding by hookworm L3 correlates with the resumption of development. PMID- 8446472 TI - Detection of Echinococcus multilocularis DNA in fox faeces using DNA amplification. AB - In order to identify Echinococcus multilocularis DNA in fox faeces for epidemiological purposes, we have developed a new method to prepare DNA suitable for PCR amplification. DNA isolation from fox excrement was performed according to a novel procedure involving lysis in KOH, phenol-chloroform extraction and a purification step on a matrix (Prep-A-Gene). The target sequence for amplification was the E. multilocularis U1 snRNA gene. PCR products were indistinguishable for 32 different E. multilocularis isolates and no signal was observed after ethidium bromide staining with DNAs from other tapeworm species, including E. granulosus. The sensitivity of amplification was monitored by the addition of E. multilocularis DNA or eggs to faeces free of E. multilocularis and was estimated to be 1 egg per 4 g of faeces. PCR products were blotted onto nylon membranes and hybridized with an internal oligonucleotide probe in order to confirm the results. Twenty nine faecal samples from foxes shot in Franche-Comte (East France) were tested. Out of 10 samples from foxes in which no E. multilocularis adult worms could be observed after necropsy, 7 were PCR positive, showing that the PCR test is more sensitive than microscopical examination. Out of 19 samples from foxes harbouring E. multilocularis adult worms, 18 were PCR positive. The remaining PCR-negative sample could be due either to the misidentification of the species of adult worm (E. granulosus and E. multilocularis), or to DNA variation between different isolates of E. multilocularis. Further work in the field should be initiated in order to confirm these results. PMID- 8446473 TI - A study of carbohydrate metabolism in the eggs (oncospheres) of the tapeworm, Hymenolepis diminuta, with special reference to glucose. AB - When incubated in vitro for 24 h, intact eggs, chemically shelled eggs (obtained by treating intact eggs with NaOCl), activated larvae (eggs in which the outer shell and inner envelope were removed), and oncospheres (activated larvae treated with papain to remove the embryophore) absorb and metabolize radioactive glucose. Intact eggs, which are covered by the impermeable shell, absorb only small amounts of exogenous radioactive glucose, while chemically shelled eggs, activated larvae, and oncospheres absorb much larger amounts. Only very small amounts of the exogenous glucose are incorporated into the ethanol-precipitable carbohydrate fraction (which would include glycogen) by any of the preparations of eggs/larvae. However, the glucose is incorporated into higher molecular weight end-products that are liberated into the incubation medium. There is a temporal shift in the ability of activated larvae and oncospheres to metabolize exogenous glucose. Activated larvae and oncospheres absorb but do not metabolize glucose during the first 8 h post-activation. Between 8 and 16 h post-activation, however, virtually all of the absorbed glucose is metabolized into higher molecular weight end-products that are liberated into the incubation media. This temporal shift suggests that activation of oncospheres and cysticercoid morphogenesis are accompanied by distinct changes in carbohydrate metabolism. PMID- 8446474 TI - A quantitative framework for evaluating the effect of community treatment on the morbidity due to ascariasis. AB - There is growing emphasis on the use of community treatment to reduce the level of morbidity caused by helminth infection. The design of chemotherapy programmes, in terms of frequency of treatment and proportion of the community treated, would be assisted by a quantitative framework which enabled the morbidity reduction achieved by different approaches to be compared. The present study describes a model developed for this purpose which embodies two innovative features. First, a quantitative score of morbidity (the proportion of individuals harbouring an intense infection) is used to rate the success of a programme and, second, the distribution of helminths in the host population is generated by a mechanism that allows the distribution to change dynamically as a function of both treatment and reinfection. The model behaviour, using values typical of Ascaris lumbricoides, indicates that the benefit derived from community chemotherapy increases non linearly with the coverage and efficacy of treatment. PMID- 8446475 TI - Children's literature: the death experience. AB - Children learn about death and dying through a variety of social, psychologic, and intellectual experiences. A review of 25 children's books provides insight into themes, values, and beliefs children learn about death through reading. PMID- 8446476 TI - Adolescents with cancer: are they at risk for suicide? AB - When the threat of cancer is imposed during a period of intense developmental changes, it is difficult to envision that an adolescent has a strong enough sense of self to survive. Yet, adolescents with cancer tend to fight to live rather than succumb to death naturally or by suicide. Possible reasons for this fight to survive can be derived from Orbach, Grass, and Glaubman's (1981) model of children's attitudes toward life and death. PMID- 8446477 TI - Temporomandibular joint dysfunction in children. AB - Despite the fact that temporomandibular joint (TMJ) dysfunction has traditionally been considered an adult disorder, there is research to document that signs and symptoms of TMJ dysfunction are prevalent in the younger population as well. Although some aspects manifest equally in both adults and children, there are unique qualities that are more relevant to pediatrics. Knowledge of the etiology, prevalence, and its clinical components may assist pediatric primary care providers in screening and caring for children with TMJ. PMID- 8446478 TI - Latex balloons: they can take your breath away. AB - Toy latex balloons are one of the leading causes of pediatric choking deaths from children's products. Education programs through community outreach are an effective way to alert professionals and parents about the risks associated with the use of latex balloons. Nurses, in a collective action, can play a major role in educating the public on balloon safety awareness. PMID- 8446479 TI - Blood administration in pediatric Jehovah's Witnesses. AB - When children of Jehovah's Witnesses are in need of a blood transfusion, the rights of the parents and the responsibility of the State may be in conflict. Understanding the basis for the Jehovah's Witnesses' beliefs and the precedents of court intervention may assist the nurse to balance the needs of the child and family with the sometimes conflicting interventions of the health care providers. PMID- 8446480 TI - Care in the absence of primary caregivers. AB - Providing home care for the pediatric patient in the absence of the primary caregiver poses risks to both the agency and nurse involved. Understanding the legal and ethical dilemmas will assist agencies in determining the appropriate measures to be taken when family respite is needed. PMID- 8446481 TI - Children's hospice care:more than a place or a concept. PMID- 8446482 TI - School-linked family health centers in health care reform. AB - Many of our nation's children have little or no access to health care, a serious problem that threatens their health and well being. If we are to provide adequate, cost-effective, and accessible health care, fundamental reform of the nation's health care system must be undertaken. PMID- 8446483 TI - Caring for families who follow alternative health care practices. AB - It is not uncommon for care providers to see families who want to follow alternative health care practices. Nurses must know about frequently encountered practices and useful nursing interventions. PMID- 8446484 TI - End of life care for infants with AIDS: ethical and legal issues. AB - Complex cases involving end-of-life care for infants with AIDS raise a variety of ethical and legal concerns. Health care providers should understand the issues involving proper treatment, including adequate relief of pain at the end of life, and a context for examining the suffering of caregivers. PMID- 8446485 TI - Down Syndrome article contained 'erroneous' information. PMID- 8446486 TI - More on RSV and Ribavirin. AB - The description of teratogenic potential in rodents, rabbits, and hamsters from environmental exposure to Ribavirin has raised concerns among caregivers. Elimination of Ribavirin use to avoid caregiver exposure is neither scientifically nor ethically justified because of its proven efficacy in the treatment of the potentially life-threatening disease of respiratory syncytial virus (RSV) in infants and young children. PMID- 8446487 TI - Factors influencing nursing care of children who are terminally ill: a selective review. AB - Care of the child who is dying is a complex and emotionally difficult nursing challenge. A review of the literature reveals a scarcity of information relating to the nurse's experience and indicates a predominant atheoretic approach. Obstacles to effective and humane terminal care exist at the personal, interpersonal, and social levels in the current health care system. PMID- 8446488 TI - The effect of two forms of learning reinforcement upon parental retention of CPR skills. AB - PURPOSE: To evaluate the effect of two forms of reinforcement upon the retention of CPR psychomotor skills in parents of high-risk infants. METHOD: A pretest/posttest, 3-group design was done with a sample of 69 parent volunteers. Reinforcement with hands on practice was given to one group; a second group had reinforcement by observing a videotape, and the third group had no reinforcement strategy. CPR skills were measured by a checklist. FINDINGS: Paired t-test showed significant differences in pretest and posttest scores for all three groups. Several CPR skills were missed on the final test more frequently than others. One way ANOVA also showed a significant difference when comparing the control group with the hands-on reinforcement group. CONCLUSIONS: Reinforcement of CPR skills should be an ongoing process. The groups who had reinforcement with hands-on practice retained the most skills. PMID- 8446489 TI - The case for legalized euthanasia. PMID- 8446490 TI - The role of military strategies in medical thinking. PMID- 8446491 TI - Institutional obstacles to clinical research. PMID- 8446492 TI - The development of awareness of iron-withholding defense. PMID- 8446493 TI - Spinal cord injury: are interleukins a molecular link between neuronal damage and ensuing pathobiology? PMID- 8446494 TI - Evolution and the biologist's daughter. PMID- 8446495 TI - The emergence of species impartiality: a medical critique of biocentrism. PMID- 8446496 TI - Nursing Times open learning programme. M6: managing the process of providing care. Part (i): being a manager (continuing education credit). PMID- 8446497 TI - Pay award. Body blow. PMID- 8446498 TI - Pay award. Yours disgustedly. Interview by Phil Cohen. PMID- 8446499 TI - Pay award. Lost hopes. PMID- 8446500 TI - Pay award. Professional position. PMID- 8446501 TI - Body politic: boxing clever. PMID- 8446502 TI - Live issues. A disturbing picture. PMID- 8446503 TI - Live issues. Emotional turmoil. PMID- 8446504 TI - Nursing development units. Taking a lead. PMID- 8446505 TI - Nursing development units. Health options. PMID- 8446506 TI - Positive responses. PMID- 8446507 TI - Water birth. Pooling information. PMID- 8446508 TI - Catheters. Men only. PMID- 8446509 TI - Mental health nursing. Speaking out. PMID- 8446510 TI - Mental health nursing. Moral minefield. PMID- 8446511 TI - A rationale for dietary intervention in postmenopausal breast cancer patients: an update. AB - In 1982, we proposed a large-scale randomized prospective trial to test the hypothesis that decreasing dietary fat intake from 38% to 20% of total calories would increase the disease-free interval and/or five-year survival rate for postmenopausal breast cancer patients. We now review new evidence from epidemiological studies, laboratory animal model studies, and preliminary feasibility trials that has accumulated over the past decade, in support of such a trial, and suggest that a more appropriate dietary goal is a reduction in fat intake to 15% of total calories. PMID- 8446512 TI - Influence of corn oil and diet on body weight, survival, and tumor incidences in F344/N rats. AB - Amount and type of fat and energy density of diets may influence tumor incidences. The purpose of this report is to summarize the influence of corn oil gavage and different nonpurified diets on spontaneous tumor incidences in 64 diet and 59 corn oil gavage control groups in two-year studies involving approximately 6,100 control Fischer 344 rats of each sex. The maximum mean body weight attained during the course of the study, survival at 106 weeks of age, and spontaneous tumor incidences of groups fed different nonpurified diets with or without corn oil gavage were summarized and evaluated for differences. Male rats fed NIH-07 open-formula diet with or without corn oil gavage had significantly higher body weight, lower survival, and higher incidence of pancreatic acinar cell tumors than rats fed commercial proprietary diets with or without corn oil gavage. Female rats fed NIH-07 diet with or without corn oil gavage had significantly higher body weights and pancreatic tumor incidences than groups fed commercial diets. Time-related trends could account for other apparent differences in tumor incidences between the groups fed commercial and NIH-07 diets. Corn oil gavage significantly increased the body weight and pancreatic tumor incidences but decreased the incidence of leukemia, a lethal tumor, which resulted in higher survival in male rats. Corn oil gavage significantly lowered the body weight and anterior pituitary tumor incidence in female rats. The pancreatic acinar cell tumor incidence appears to be due to a combination of fat intake and body weight. PMID- 8446513 TI - beta-Carotene uptake, metabolism, and distribution in BALB/c 3T3 cells. AB - Although a growing number of epidemiological studies indicate that dietary beta carotene has anticarcinogenic activity, the mechanism(s) of beta-carotene protection remains to be definitively established. In this context, in vitro studies of beta-carotene have been, and continue to be, valuable. We examined the following critical features in designing an in vitro system for studying the protection action of beta-carotene: 1) form of beta-carotene used for cellular uptake, 2) cellular metabolism of beta-carotene, and 3) subcellular distribution of beta-carotene. It was determined that beta-carotene added to medium in a water dispersible formulation is readily taken up by BALB/c 3T3 cells and is located predominantly in cellular membranes. Cellular uptake of beta-carotene added to medium in an organic solvent is greatly reduced. It was also found that intracellular retinol increased significantly after a three-day exposure of BALB/c 3T3 cells to media containing beta-carotene. This result suggests that the ability to metabolize beta-carotene to retinoids is not limited to cells of intestinal origin. The results and methodology described here will be useful in the rational design of in vitro assays for elucidating the mechanism(s) of beta carotene protective effects at the cellular level. PMID- 8446514 TI - The effects of soluble-fiber polysaccharides on the adsorption of a hydrophobic carcinogen to an insoluble dietary fiber. AB - Dietary fiber is believed to decrease the incidence of colorectal cancer, but not all types of fiber are equally protective. Dietary fibers may be divided broadly into insoluble and soluble fibers, and there is evidence from animal experiments that the latter not only fails to protect against colorectal cancer but may enhance its development. Adsorption of carcinogens to insoluble dietary fiber in the intestinal tract is one of the mechanisms by which dietary fiber is believed to protect against colorectal cancer. In previous in vitro experiments, we showed that the hydrophobic carcinogen 1,8-dinitropyrene (DNP) adsorbs to insoluble plant cell wall components (insoluble dietary fibers). Soluble polysaccharides (pectic polysaccharides) extracted from the walls of parenchyma cells of dicotyledonous plants were found to maintain DNP in aqueous solutions and decrease its adsorption to insoluble wall components. In the present study, we examined a commercial preparation of pectin and seven other soluble-fiber polysaccharides with diverse structures for their effects on the distribution of DNP. Many of these are used as emulsifiers and stabilizers in the food industry. They all maintained DNP in aqueous solution and decreased its adsorption to alpha cellulose, which we used as an example of an insoluble dietary fiber. Gum arabic was the most effective and kappa-carrageenan the least. The capacity of the polysaccharides to act as emulsifiers and stabilizers may explain their effects on DNP distribution. The monosaccharide glucose and the disaccharide cellobiose had no effect on the distribution of DNP. These results indicate three possible mechanisms by which soluble-fiber polysaccharides may enhance the development of colorectal cancer. First, because they reduce the ability of insoluble dietary fibers to adsorb hydrophobic carcinogens, more carcinogens may enter the colon maintained in solution than adsorbed onto insoluble fibers. Second, if soluble fiber polysaccharides are maintaining hydrophobic carcinogens in solution and these polysaccharides are degraded by bacterial enzymes in the colon, then the carcinogens may come out of solution and be deposited onto the mucosal surface of the colon. Third, soluble-fiber polysaccharides may cross the intestinal epithelium and carry with them carcinogens maintained in solution. These studies have important consequences for nutrition, because soluble-fiber polysaccharides represent a common component of foods. PMID- 8446515 TI - Dietary carotenoids influenced biochemical but not morphological changes in adult male rats fed a choline-deficient diet. AB - In a study of the effects of carotenoids, canthaxanthin (CA), beta-apo-8' carotenal (BA), or beta-carotene in an extract of Spirulina-Dunaliella algae (AE) was fed at 0%, 0.1%, or 0.2% in a choline-deficient (CD) diet. In each of eight groups, 10 adult male Fischer 344 rats were fed diets with designated carotenoid sources and levels or a choline-sufficient diet for 12 weeks. Carotenoids altered some of the changes induced by the CD diet. Increases in enlargement of fatty livers and low plasma cholesterol levels occurred in rats fed 0.2% BA. Plasma retinol was further reduced 35% by BA or AE. BA and AE increased liver total vitamin A about 80% and 305%, respectively. Liver lipid peroxidation was enhanced and plasma alpha-tocopherol was reduced further by 1.0% AE. AE, BA, and CA (mg/g fat) depressed liver alpha-tocopherol about 49%, 67%, and 78%, respectively. The decreased liver alpha-tocopherol was concurrent with an increase in carotenoid stores of CA > BA > AE. Histopathological examination of sections of liver tissue by light microscopy showed fatty and cirrhotic changes in all rats fed CD diets. Histochemical evaluation based on a semiquantitative assay revealed a marked increase in peroxisome enzyme activity in the livers of all CD rats. None of the carotenoids appeared to have any effect on the development of morphological changes in the liver. Although carotenoids can function as antioxidants, they did not prevent changes observed in rats fed CD diets. PMID- 8446516 TI - Chemoprevention of benzo[a]pyrene-induced forestomach cancer in mice by natural phthalides from celery seed oil. AB - Bioassay-directed fractionation of celery seed oil from the plant Apium graveolens (Umbelliferae) led to the isolation of five natural products, including d-limonene, p-mentha-2,8-dien-1-ol, p-mentha-8(9)-en-1,2-diol, 3-n butyl phthalide, and sedanolide. Of these compounds p-mentha-2,8-dien-1-ol,3-n butyl phthalide, and sedanolide exhibited high activities to induce the detoxifying enzyme glutathione S-transferase (GST) in the target tissues of female A/J mice. 3-n-Butyl phthalide and sedanolide (20 mg/dose every two days for a total of 3 doses) increased GST activity 4.5-5.9 and 3.2-5.2 times over the controls in the mouse liver and small intestinal mucosa, respectively. At the same dose, p-mentha-2,8-dien-1-ol induced GST activity about 3.7-fold above that of the controls. Thus, these compounds were further tested for their ability to inhibit benzo[a]pyrene- (BP) induced tumorigenesis in mice. After treatment with 3-n-butyl phthalide and sedanolide, the tumor incidence was reduced from 68% to 30% and 11%, respectively. About 67% and 83% reduction in tumor multiplicity was also observed with 3-n-butyl phthalide and sedanolide. p-Mentha-2,8-dien-1-ol produced only a small or no significant reduction of forestomach tumor formation. The data indicating that 3-n-butyl phthalide and sedanolide were both active in tumor inhibition and GST assays suggested a correlation between the inhibitory activity and the GST-inducing ability. The phthalides are known to determine the characteristic odor of celery. The results suggest that phthalides, as a class of bioactive natural products occurring in edible umbelliferous plants, may be effective chemopreventive agents. PMID- 8446517 TI - Lipid metabolism in cachectic tumor-bearing rats at different stages of tumor growth. AB - Rates of lipogenesis and lipoprotein lipase (LPL) activity were measured in liver, adipose tissue, heart, and tumor at several stages during 10 days of palpable growth of a transplantable Leydig cell tumor in rats. This model showed the same characteristics as human cancer cachexia, including anorexia, weight loss, and muscle wasting. Comparison with pair-fed controls showed that the rate of loss of body fat was greater than could be explained by anorexia alone. The rate of lipogenesis tended to decrease during the later stages of tumor growth, particularly in the liver, where there was a statistically significant reduction on Days 5 and 10. This may be largely attributable to decreased availability of substrates caused by decreasing food intake and increasing glucose uptake by the tumor. There was a significant decrease in plasma glucose concentration by Day 10. In contrast, LPL activity in adipose tissue was depressed from the earliest stage of tumor growth, and this is likely to be a major cause of lipid depletion in cancer. There was no difference in adipose tissue LPL activity between the fed and postabsorptive states in the tumor-bearing rats, indicating that the normal response to nutrient intake was impaired. Thus, treatment of cancer cachexia should concentrate on normalizing the metabolic response to nutrient ingestion. PMID- 8446519 TI - Intracardiac emergency defibrillation for refractory ventricular fibrillation during implantation of cardioverter defibrillators with nonthoracotomy lead systems. AB - Implantable cardioverter defibrillators (ICDs) are being implanted in increasing numbers. At intraoperative defibrillation threshold tests refractory ventricular fibrillation (VF) requiring emergency open chest resuscitation is a major concern during implantation of nonthoracotomy ICD lead systems. A new method of high energy endocardial/extrathoracic defibrillation via the implanted ICD transvenous defibrillation electrode (TDE) was used to terminate refractory VF. During implantation of ICD with TDE in 20 patients refractory VF occurred in two patients. The arrhythmia was terminated with endocardial/extrathoracic defibrillation in both cases, and no complications were observed. PMID- 8446518 TI - Effects of high-fat diet on incidence of spontaneous tumors in Wistar rats. AB - In a 2.5-year carcinogenicity study, two groups, both including male and female Wistar rats, were fed two different diets with 4% and 16% fat. In addition to 4% soybean oil, the high-fat diet contained 12% mono- and diglycerides, of which 85% was stearic acid and 13% palmitic acid. There was no difference in food consumption, body weight, weight gain, and longevity between the two groups. A statistically significant increase in the incidence of tumors in the high-fat group was seen in fibroadenoma of the mammae (female, p = 0.05). No statistically significant difference was seen when the incidence of benign mammary tumors (adenomas and fibroadenomas) was combined, just as the overall incidence of mammary tumors (adenomas, fibroadenomas, and adenocarcinomas) was not significantly different between the groups. A statistically significant decrease in the incidence of tumors in the high-fat group was seen in adenoma of the parathyroid gland (male, p = 0.04) and medullary carcinoma of the adrenal gland (male, p = 0.04). Combining the incidence of benign and malignant tumors of the adrenal medulla led to a further increase in the level of significance (p = 0.02). The present study showed that a high-fat diet influenced the tumor incidence in certain organs of rats. However, the overall differences in tumor incidence between rats fed the low- and the high-fat diet are considered marginal. Therefore we were not able to confirm or deny the hypothesis that a high-fat diet promotes the development of cancer. It should be noted that, in our study, fat accounted for about 30% of the total energy in the high-fat diet. This is much below the amount of fat normally found in the western diet but corresponds well to the level recommended for human intake. In addition, the rats fed the high-fat diet did not gain more weight, even though no difference was recorded in food consumption (g/kg body wt) between the groups. PMID- 8446520 TI - Postpartum mood disorders. A startling contrast to the joy of birth. AB - More than half of new mothers may be affected by mood disorders after childbirth. Possible causes and recommended management depend on the type of disorder and its severity. In this article, Dr Knops discusses recognition, prevention, and management of three types of postpartum mood disorders as well as the need for support for a woman and her family at this vulnerable time. PMID- 8446521 TI - Enterococcal infections. The increasing threat of nosocomial spread and drug resistance. AB - Enterococcal nosocomial infections are becoming more common. Their multiple resistance mechanisms to various antibiotics pose serious therapeutic problems. Despite 40 years of intense development of antimicrobial agents, no agent surpasses the synergistic effects of a combination of a penicillin or vancomycin plus an aminoglycoside for treatment of enterococcal infections. New agents that have bactericidal activity against enterococci are needed as the incidence of resistant strains increases. PMID- 8446522 TI - Bill puts Hillary in charge of overhauling our healthcare system. PMID- 8446523 TI - Drug interactions in diabetic patients. The risk of losing glycemic control. AB - Any number of prescription and over-the-counter medications, including diuretics and salicylates, can affect glycemic control in diabetic patients. In addition, patients being treated with either insulin or sulfonylurea risk hypoglycemic coma or death if they ingest large quantities of alcohol. The authors of this article discuss the medications most likely to be a problem and provide lists of agents associated with hypoglycemia and hyperglycemia. PMID- 8446524 TI - Health insurance proposal. PMID- 8446525 TI - A difficult promise. PMID- 8446526 TI - Tuberculosis. The primary care physician's role in eradication. AB - The resurgence of tuberculosis in the United States presents a challenge for primary care physicians. The disease remains concentrated in the growing population of socioeconomically disadvantaged persons, immigrants from areas where drug resistance is common, certain racial groups, persons in extended-care facilities, alcohol and drug abusers, and persons infected with the human immunodeficiency virus. Because people in these groups are much less likely than others to seek regular medical care, it is difficult to identify and treat active tuberculosis in these populations. Contacts of patients with tuberculosis are equally difficult to identify. Active intervention by primary care physicians- including tuberculin screening, prophylactic therapy, treatment of active disease, and follow-up--is needed to help achieve the goal of eradicating tuberculosis. PMID- 8446527 TI - Management of impotence. Diagnostic considerations and therapeutic options. AB - Impotence affects an estimated 10 million American men. The cause is usually organic in men over age 50; psychogenic impotence is more common in younger men. Vascular disease is the most common cause of impotence. Evaluation in patients with impotence includes thorough history taking and diagnostic testing. Once the cause of impotence is determined, appropriate management can be chosen. Current therapeutic options include vacuum tumescence devices, self-injection, oral therapy, psychotherapy, and penile prostheses. PMID- 8446528 TI - Evaluation of acute knee injuries. AB - Early, accurate diagnosis and aggressive treatment are important in returning a patient with an acute knee injury to full function. Although many problems, such as acute tendinitis and mild sprains, can be simply treated with short periods of rest, some disabilities may be chronic or recurrent and require more invasive treatment. Many acute injuries necessitate emergency treatment or early surgical intervention. Detailed history taking and a thorough and knowledgeable examination of the knee are the key elements in evaluation. Special tests and radiographic studies are also helpful. PMID- 8446529 TI - Ankle injuries. Tips from sports medicine physicians. AB - In dealing with an ankle sprain, worrisome features are few but important to recognize. A "pop" heard or felt at the time of injury, a prolonged course, or a history of several previous injuries are all of concern. Medial tenderness on palpation, positive results on a squeeze test, or markedly positive results on stress testing are also indicators of severe injuries, which may require referral for treatment. Stress testing by an experienced clinician is appropriate for chronic or severe cases. Otherwise, treatment of the acute, uncomplicated ankle injury is straightforward, focusing on early mobilization, rehabilitation, and protection. PMID- 8446530 TI - A checklist for evaluation of HIV-infected patients. AB - To aid in making care of HIV-infected patients part of your office routine, Dr Coodley presents here a checklist that combines the various clinical aspects of initial management. Covering the steps from the history to plans for follow-up, this article should allay anxiety and promote confidence in your entire staff by explaining the necessary basics in a simple-to-read format. PMID- 8446531 TI - Extrahepatic biliary tract obstruction. Modern methods of management. AB - Extrahepatic biliary tract obstruction can often be diagnosed by means of thorough history taking, physical examination, and basic laboratory data. The cause of obstruction can be best defined and is often best treated by biliary endoscopy and/or percutaneous radiologic techniques, which appear to be safer than surgical decompression. PMID- 8446532 TI - Acute bleeding from peptic ulcers. How to restore hemostasis and prevent recurrence. AB - Prompt resuscitation is the cornerstone in management of acute upper gastrointestinal bleeding. Endoscopy has become the diagnostic procedure of choice because it offers the chance for hemostatic therapy. For patients in whom endoscopy reveals actively bleeding peptic ulcers or nonbleeding peptic ulcers or nonbleeding ulcers with visible vessels, endoscopic therapy decreases the likelihood that the patient will bleed further, require surgery, or die. Patients with critical illnesses requiring intensive care should receive prophylaxis against stress ulcers. Long-term management of bleeding peptic ulcer disease includes educating patients to quit smoking, avoid non-steroidal anti inflammatory drugs, and comply with maintenance therapy with a histamine2 receptor antagonist. PMID- 8446533 TI - Iron deficiency anemia. Every case is instructive. AB - Awareness of subtle symptoms of mild iron deficiency is increasing, but unsuspected iron deficiency is a persistent problem, especially among certain groups, such as menstruating women and milk-fed infants. The diagnosis must be clearly established through appropriate testing, and an underlying cause should always be sought. Useful tests include determination of serum ferritin and iron levels and of iron-binding capacity. A nomogram is available that correlates the serum ferritin value with the degree of inflammation present, but in some patients, bone marrow aspiration and iron staining is still required. When oral iron therapy is undertaken, an appropriate non-enteric-coated, non-sustained release preparation should be chosen. Gradually increasing the amount of iron supplementation and taking the tablets with meals help limit side effects and ensure patient compliance. Iron therapy should be continued for 6 months after the hemoglobin level returns to normal so that total iron stores are replaced. Follow-up to ensure that iron deficiency anemia has not recurred and that the diagnosis was correct is required. PMID- 8446534 TI - Keep your eyes on Washington--and don't blink! PMID- 8446535 TI - Hypertension in obese patients. AB - Obesity and hypertension often coexist. The waist-hip ratio has been found to be a more accurate predictor of hypertension than either body weight or body mass index. A waist-hip ratio of 0.85 or more in men and 0.75 or more in women is a significant cardiovascular risk factor. Insulin also probably has an important role in the pathogenesis of hypertension in obese patients. Treatment of hypertension in overweight patients begins with weight loss, which is frequently achieved by combining caloric restriction and exercise. Such commonly used drugs as angiotensin-converting enzyme inhibitors, calcium blockers, alpha blockers, and beta blockers are appropriate for medical treatment of these patients. PMID- 8446536 TI - Cervical spine radiography after blunt trauma. Is it always needed? AB - In trauma cases, the mere presence of a cervical immobilization device is not an indication for radiography of the cervical spine. High-yield radiographic criteria have been prospectively determined for cases of blunt trauma, and these identify individuals at low risk for cervical spine injuries. Cervical spine radiography is not required for patients who are alert, cooperative, and nonintoxicated and do not have neurologic deficits, cervical signs or symptoms, antecedent spinal mobility disorders, or distracting injuries. Cervical spine radiography alone does not ensure detection of all injuries. Adequate history taking and careful examination are always essential and may dictate additional studies. PMID- 8446537 TI - Pigeon-breeder's lung. Extensive workup clarifies the clinical picture. AB - Pigeon-breeder's lung should be included in the differential diagnosis when patients present with interstitial lung disease or intermittent cough and dyspnea. No single test confirms the diagnosis. Rather, careful attention must be given to results of history taking, physical examination, pulmonary function and precipitin testing, chest radiography, and, if indicated, lung biopsy. Symptoms usually resolve when exposure to suspected antigens is avoided. PMID- 8446538 TI - Disorders of water and sodium balance. AB - The serum sodium concentration reflects a patient's relative water balance and thus determines if the patient needs more or less water than normal maintenance needs would dictate. The serum sodium concentration has no bearing on whether a patient requires sodium restriction or saline administration. Rather, the sodium/saline balance is determined by clinical assessment of the patient's extracellular fluid volume. Physicians must clearly understand the principles involved when assessing a patient's water and sodium needs. After maintenance water needs and any foreseeable ongoing losses have been factored in, an intelligent plan of fluid management can be initiated. Frequent reassessments, with serial weight measurements, clinical evaluations of extracellular fluid volume status, and determinations of serum sodium concentration, are essential to determine if the desired therapeutic goals are being reached. PMID- 8446539 TI - Caring for patients after coronary bypass surgery. Follow-up tips for primary care physicians. AB - Primary care physicians are often faced with follow-up care of patients who have had coronary artery bypass graft surgery. Familiarity with possible cardiac, pulmonary, neurologic, and infectious complications is important, and an open line of communication with the consulting cardiologist and the cardiac surgeon is essential. Modification of coronary risk factors is one of the greatest challenges after bypass surgery. The primary care physician plays the major role in directing and monitoring life-style changes that reduce the risk of progressive coronary atherosclerosis. Recurrent myocardial ischemia after bypass surgery should be evaluated fully and is often responsive to nonsurgical therapies, including percutaneous transluminal coronary angioplasty. PMID- 8446540 TI - Geriatric psychopharmacology. A primary care challenge. AB - Optimum therapy with psychopharmacologic agents in geriatric patients requires an appreciation of the elderly's increased predisposition to emotional disorders and their unique sensitivity to adverse drug-drug interactions. Although nonpharmacologic approaches should be considered, adjunctive use of psychoactive medications can assist the physician to break the "negative cycle" of emotional distress that often goes untreated in this age-group. Knowledge of which psychotropic medications are preferred for use in the elderly allows primary care physicians to make timely and successful therapeutic interventions. Consultation with a psychiatrist should be considered for complicated cases. PMID- 8446541 TI - Clinton's health team. PMID- 8446542 TI - Clinton's health team. PMID- 8446543 TI - Fluoroquinolones and drug interactions. PMID- 8446544 TI - Nonsteroidal anti-inflammatory drugs. Tailoring therapy to achieve results and avoid toxicity. AB - When used appropriately, non-steroidal anti-inflammatory drugs (NSAIDs) are safe and effective for treating pain and inflammation. NSAIDs that block both the lipoxygenase and cyclooxygenase pathways may be advantageous in some patients. New classes of NSAIDs that may have a more favorable safety profile than older agents may improve patient outcome. However, all patients receiving NSAIDs, especially the elderly, should be carefully monitored for possible drug-related complications. PMID- 8446545 TI - Acute mesenteric ischaemia. PMID- 8446547 TI - Stroke in patients aged over 75 years: outcome and predictors. AB - The outcome and predictors of stroke rehabilitation were studied prospectively in 96 patients (mean age 81.3 +/- 5.4 years) admitted to geriatric wards from a well defined area over one year. Of these, 32 (33%) died (median survival 11 days), 52 (54%) returned home (median hospital stay 69 days) and 12 (13%) required long term care (median hospital stay 164 days). Deaths and discharges showed a bimodal pattern; nearly 40% of the patients died or were discharged within 2 weeks of admission. Early death correlated with level of consciousness (P = 0.02), neurological deficit (P = 0.01) and prestroke Barthel scores (P = 0.04) on admission. Patients with right- rather than left-sided hemiparesis (P = 0.02), good motor power (P = 0.002) and without sensory deficit/inattention (P = 0.002) were discharged early. Discharge home was adversely affected by poor awareness of deficit (P = 0.02), hemianopia (P = 0.03) and incontinence (P = 0.02) assessed at 2 weeks. Stroke survivors with Barthel score < 6 and Mental Test Score < 4 at 2 weeks after stroke required long-term care. PMID- 8446546 TI - Diagnostic tests in pleural effusion--an update. PMID- 8446548 TI - In support of nitrate ointment for patients with acute myocardial infarction. PMID- 8446549 TI - Cigarette smoking and Helicobacter pylori infection. AB - The direct urease test was used in 462 patients with normal upper digestive tracts, 108 with duodenal ulcers and 43 with gastric ulcers who attended for upper digestive endoscopy in a prospective study. There was a strong association between Helicobacter pylori infection and current cigarette smoking in patients with normal endoscopy (49.6% vs 35.5%, P < 0.01). The associations of peptic ulcer both with H. pylori infection and cigarette smoking were also confirmed. The excess of peptic ulcer disease in cigarette smokers may be explained by their increased susceptibility to H. pylori infection. PMID- 8446550 TI - The prevalence and nosocomial acquisition of Clostridium difficile in elderly hospitalized patients. AB - Rectal swabs obtained from 10 of 49 chronic-care geriatric patients were positive for Clostridium difficile, for a prevalence rate of 20.4%. Simultaneous sampling of 29 patients in an acute geriatric ward revealed four colonized patients, for a prevalence rate of 13.7%. A prospective study of C. difficile colonization in 100 consecutive patients admitted to an acute geriatric ward was carried out. All patients were sampled upon admission and biweekly during hospitalization. Two patients (2%) were positive on admission, and 12 of the 98 initially negative patients became colonized, representing a nosocomial acquisition rate of 12.2%. A major determinant for C. difficile colonization in asymptomatic patients appears to be length of hospitalization. Previous antibiotic administration was not found to be a significant factor. PMID- 8446551 TI - Acute mesenteric ischaemia: the continuing difficulty in early diagnosis. AB - Five cases of acute intestinal ischaemia due to occlusion of the superior mesenteric artery, all with a delay in diagnosis, are reported here. These cases illustrate the continuing difficulties, in clinical practice, in recognizing mesenteric ischaemia before intestinal infarction has occurred, despite the clinical awareness of this condition. PMID- 8446553 TI - The thrombolytic effect of heat. PMID- 8446552 TI - Paracetamol cardiotoxicity. AB - A 29 year old man with a significant paracetamol overdose was found to have an abnormal electrocardiograph which, in the absence of hepatic encephalopathy, was considered due to a direct cardiotoxic effect of the drug. A functional coronary insufficiency resulting from inhibition of endothelium-derived relaxing factor secondary to depletion of sulphydryl groups is postulated, and it is suggested that in paracetamol poisoning evidence of cardiotoxicity alone may be sufficient justification for treatment with acetylcysteine. PMID- 8446554 TI - Developing medical education. AB - This article reviews the current state of undergraduate and postgraduate medical education, and suggests changing the educational methods used rather than rearranging the content of courses. A learner centred approach is described, and its applications to postgraduate medical education discussed. Some research and development implications are considered. PMID- 8446556 TI - Pyomyositis complicating pneumococcal meningitis. AB - A young male with a previous splenectomy presented with Streptococcus pneumoniae meningitis complicated by pyomyositis. Pneumococcal meningitis in asplenic patients is well recognized, but the association of pyomyositis as a complication has not to our knowledge been previously reported. PMID- 8446555 TI - Atypical manifestations of ruptured abdominal aortic aneurysms. PMID- 8446557 TI - Cervical ribs: a cause of distal and cerebral embolism. AB - The thoracic outlet syndrome occurs when the neurovascular structures are compressed as they traverse the thoracic outlet. Degenerative changes can occur in the subclavian artery and the vessel may become a source of embolism with the risk of acute or chronic upper limb ischaemia. Rarely, distal thromboembolism in the thoracic outlet syndrome may be associated with retrograde flow when there is the added risk of cerebral thromboembolism. PMID- 8446558 TI - Idiopathic calcification of the basal ganglia. AB - Idiopathic calcification of the basal ganglia is a rare disorder characterized by neuropsychiatric abnormalities, a movement disturbance of parkinsonian and/or choreoathetoid type and dense calcification of the basal ganglia. We report a 60 year old patient diagnosed as having delusional disorder and tardive dyskinesia who was subsequently found to be suffering from idiopathic calcification of the basal ganglia. PMID- 8446559 TI - Pulmonary alveolar microlithiasis presenting with chronic cough. AB - A case of a 10 year old boy with pulmonary alveolar microlithiasis is presented. Although most children with this disease are asymptomatic, our patient had persistent cough for more than 3 years. It is likely that his chronic cough was a direct consequence of the disease. PMID- 8446560 TI - Polyglandular autoimmune syndrome type III associated with coeliac disease and sarcoidosis. AB - A female patient demonstrating a previously not reported constellation of polyglandular autoimmune syndrome type III (including autoimmune thyroiditis, Graves' ophthalmopathy, insulin-dependent diabetes mellitus and vitiligo), coeliac disease and sarcoidosis is described. This may be a random association but might also indicate a common immunological and/or genetic disturbance. PMID- 8446561 TI - Obstructive uropathy due to extramedullary haematopoiesis in beta thalassaemia/haemoglobin E. AB - An 18 year old woman with beta thalassaemia/haemoglobin E developed a large pelvic tumour resulting in bilateral obstructive uropathy. Technetium-99m sulphur colloid marrow image, computed tomographic scan of the abdomen and needle biopsy of the mass confirmed the diagnosis of extramedullary haematopoiesis. Although radiation is the treatment of choice for decompression, the mass in this patient did not respond satisfactorily due to its multiple area of tumour autoinfarction. Obstructive uropathy due to extramedullary erythropoiesis has not to our knowledge been previously described. PMID- 8446562 TI - Malignant phaeochromocytoma and hypercalcaemia. AB - We describe a case of hypercalcaemia secondary to recurrent malignant phaeochromocytoma. Parathyroid-related protein (PTHrp 1-86) immunoreactivity was identified in plasma and PTHrp was identified by immunocytochemistry in tumour tissue. PMID- 8446563 TI - Antifibrinolytic therapy for haemoptysis related to bronchial carcinoma. PMID- 8446564 TI - The role of Candida albicans in the pathogenesis of food-intolerant irritable bowel syndrome. PMID- 8446565 TI - Listeria meningitis--neurological and psychiatric sequelae. PMID- 8446566 TI - Fetal blood sampling and cytogenetic abnormalities. AB - From September 1984 to April 1991, we performed cytogenetic analysis on fetal blood samples from 214 second- and third-trimester pregnancies. One hundred and thirty-four cases were referred to consider the possibility of chromosomal mosaicism following amniocyte studies. The confirmation rate of mosaicism is at 0 per cent (0/9), 1.4 per cent (1/70), and 40 per cent (22/55) for cases of level I, level II, and level III mosaicism, respectively. Four out of 17 cases were positive for the diagnosis of fragile X syndrome. Of 63 cases with abnormal ultrasound findings, blood disorders, or other genetically related clinical conditions, 11 were found to have a chromosome abnormality. Fetal blood sampling is a valuable adjunct to other methods in the prenatal diagnosis of chromosomal mosaicism or pseudomosaicism. It is also useful when rapid cytogenetic diagnosis is desired because of malformations detected in pregnancies at a late gestational age. PMID- 8446567 TI - Prenatal diagnosis of syndromes associating albinism and immune deficiencies (Chediak-Higashi syndrome and variant). AB - We have successfully undertaken the prenatal diagnosis of two hereditary syndromes associating albinism and immune defects. Because the genes responsible for these diseases have not yet been mapped and the immune abnormalities are too subtle to be diagnosed in utero, the prenatal diagnosis was made using a morphological approach. In the case of Chediak-Higashi syndrome, it was based on light microscopic examination of the hair shaft and on light and electron microscopic study of polymorphonuclear cells. In the syndrome associating immune deficiency and partial albinism, the Griscelli syndrome, only examination of the hair was feasible. The diagnosis was negative in 12 fetuses at risk and positive in four. PMID- 8446568 TI - Early genetic amniocentesis--4 years' experience. AB - Four hundred and thirty early amniocenteses (EAC) from 10 to 14 weeks' gestation were compared with 300 routine amniocenteses (RAC) from 15 weeks' gestation (control A) and 733 routine amniocenteses from 16 to 18 weeks' gestation (control B) with regard to success rates, various growth parameters, and cytogenetic results. Using both in situ and trypsinization techniques, the success rate was 99.8 per cent for EAC versus 100 per cent for RAC. The average turn-around time for establishing a diagnosis was 8.4 days in EAC versus 8.3 days in 15 weeks' specimens (n.s.) and 7.7 days in 16 to 18 weeks' specimens (p < 0.0001) for the last 200 samples. The banding quality of early specimens compared favourably with that of controls (both 500-550 bphs) and was much better than that in long-term cultured chorionic villus sampling (CVS) (350-400 bphs). For level I and level II mosaicism, no statistically significant differences were noted between EAC and control group A. Comparing EAC with control group B, a significant increase in the number of numerical and structural single cell aberrations was observed (p < 0.025 and p << 0.001, respectively), whereas for multiple cell aberrations only the increase in numerical aberrations was statistically significant (p << 0.001) (chi 2-test). Clinical problems arising from the detection of mosaicism were solved in all cases by investigating parallel cultures. It is concluded that early amniocentesis is a reliable procedure which permits prenatal diagnosis of numerical and structural chromosome aberrations to a high standard. PMID- 8446569 TI - Prospective maternal serum human chorionic gonadotropin screening for the risk of fetal chromosome anomalies and of subsequent fetal and neonatal deaths. AB - A prospective study of maternal serum human chorionic gonadotrophin (hCG) measurement for the selection of pregnancies with an increased risk of fetal trisomy 21 was undertaken in 24,000 pregnancies from 1 January 1989 to 31 December 1990. Maternal serum was sampled at 15-18 weeks of gestation. hCG was measured in one laboratory, with one technique. This 'hCG high level' technique was developed for this screening. Amniocentesis was offered to each woman with a maternal serum hCG level above the cut-off. The follow-up of the pregnancies is known in 92 per cent of cases. The combination of hCG values and maternal age gave a detection efficiency of 63 per cent for trisomy 21 with rates of amniocentesis of 30 per cent for patients aged 37 years. 20 per cent for patients aged 35 or 36 years, and 5 per cent for patients under 35 years of age. Based on this prospective study, an individual risk was calculated combining the serum hCG value and maternal age. Seventy-four per cent of trisomy 13, trisomy 18, triploidy, and 5p-deletion were detected either in the same selected group of women or in combination with ultrasonography performed when hCG values were very low. The follow-up study showed that women who had high or low hCG values represented a group at high risk for fetal or perinatal death. PMID- 8446570 TI - Detection of both the normal and mutant alleles in single cells of individuals heterozygous for the sickle cell mutation--prelude to preimplantation diagnosis. AB - As a preliminary step to preimplantation diagnosis of sickle cell disease in unfertilized eggs or 8-cell embryos of heterozygous parents, we established quality control for detection of the mutant and normal alleles of the beta haemoglobin gene using single buccal cells. Efficient polymerase chain reaction (PCR) amplification of a 680 base pair sequence of the beta-globin gene spanning the site of the sickle cell mutation was obtained for 79 per cent of single heterozygous cells. In 71 per cent of cases, both alleles were detected. With this current efficiency, we predict that a clinical preimplantation diagnosis at the 8-cell embryo stage could be carried out safely and reliably for a couple at risk of transmitting sickle cell disease to their children. PMID- 8446571 TI - Umbilical cord haemangioma associated with an eruptive cutaneous haemangioma in a female infant. AB - We report a female infant noted prenatally to have an umbilical cord mass. At birth, a labial strawberry haemangioma was noted. She subsequently developed an abdominal mass which was discovered to be a proliferating haemangioma, continuous with both the labial and the umbilical stump lesions. PMID- 8446572 TI - Prenatal diagnosis of congenital cystic adenomatoid lung malformation: a report of seven cases. AB - Six cases of macrocystic and one case of microcystic congenital adenomatoid lung malformation were diagnosed by ultrasound between 20 and 31 weeks of gestation. Combined polyhydramnios and fetal hydrops was present in three cases, polyhydramnios alone in one case, and isolated fetal hydrops also in one case. In the remaining two cases, both polyhydramnios and fetal hydrops were absent. Fetal outcome was poor, i.e., two terminations of pregnancy, three early neonatal deaths, and two survivors. PMID- 8446573 TI - Prenatal sonographic diagnosis of metastatic neuroblastoma: report of a case and review of the literature. AB - Congenital malignant tumours are rare. Neuroblastoma is the most common solid tumour, accounting for about 30-50 per cent of tumours evident during the neonatal period. A case of metastatic, rapidly growing neuroblastoma, diagnosed prenatally by ultrasound at 32 weeks' gestation, is presented. PMID- 8446574 TI - Supramolecular chemistry. PMID- 8446575 TI - Good vibes. PMID- 8446576 TI - Strategies for the identification of interacting proteins. AB - Many problems in modern biology involve complex arrays of interacting protein and, in some cases, RNA molecules. The initial challenge facing investigators is to identify the important players that drive the process under study. This difficult task is ameliorated somewhat by the development of methods designed to keep pace with the magnitude of this challenge. I have outlined a few of these approaches at the cutting edge of cloning interacting proteins. A perhaps more daunting prospect is to dissect the important molecules once they are in hand, to identify key interactions, and, ultimately, to move to an understanding of function in cells. For this, of course, all of the tools of genetics, biochemistry, and molecular biology, extant and yet to be developed, will have to be tapped. PMID- 8446577 TI - Shared thematic elements in photochemical reaction centers. AB - The structural, functional, and evolutionary relationships between photosystem II and the purple nonsulfur bacterial reaction center have been recognized for several years. These can be classified as "quinone type" (type II) photosystems because the terminal electron acceptor is a mobile quinone molecule. The analogous relationship between photosystem I and the green sulfur bacterial (and helicobacterial) reaction centers has only recently become clear. These can be classified as "iron-sulfur type" (type I) photosystems because the terminal electron acceptor consists of one or more bound iron-sulfur clusters. At a fundamental level, the quinone type and iron-sulfur type reaction centers share a common photochemical motif in the early process of charge separation, leading to the speculation that all photochemical reaction centers have a common evolutionary origin. This review summarizes the current state of knowledge in comparative reaction center biochemistry between prokaryotic bacteria, cyanobacteria, and green plants. PMID- 8446578 TI - Sequencing two DNA templates in five channels by digital compression. AB - By applying algebraic coding methods to the Sanger dideoxynucleotide procedure, DNA sequences of two templates can be determined simultaneously in only five reactions and data channels. A 5:2 data compression is accomplished by instantaneous source coding of nucleotide sequence pairs into one set of 5-bit block codes. A general algebraic expression, 2n-1 > or = 4f, describes conditions under which f DNA templates can be sequenced using n channels. Such compression sequencing is accurate and efficient, as demonstrated by manual 35S autoradiographic detection and automated on-line analysis using fluorescent labeled primers. Symmetric 5:2 compression is especially useful when comparing two closely related sequences. PMID- 8446579 TI - A selective transcriptional induction system for mammalian cells based on Gal4 estrogen receptor fusion proteins. AB - Most mammalian cells neither express any Gal4-like activity nor endogenous estrogen receptor, thus rendering estrogen an inert signal for them. For these two reasons we have developed a selective induction system based on the estrogen regulable transcription factor Gal-ER. Gal-ER consists of the DNA-binding domain of the yeast Gal4 protein fused to the hormone-binding domain of the human estrogen receptor and hence should exclusively regulate a transfected gene under the control of a Gal4-responsive promoter in mammalian cells. Two major improvements of this induction system were made. First, a synthetic Gal4 responsive promoter was constructed which consisted of four Gal4-binding sites, an inverted CCAAT element, a TATA box, and the adenovirus major late initiation region. This promoter showed extremely low basal activity in the absence and high inducibility in the presence of ligand-activated Gal-ER. Second, the transcription factor Gal-ER was rendered more potent and less susceptible to cell type-specific variation by fusing the strong activating domain of the herpesvirus protein VP16 onto its C terminus. In response to estrogen, Gal-ER-VP16 induced the Gal4-responsive promoter at least 100-fold in transiently transfected NIH 3T3 and P19 cells. Rat fibroblast cell lines expressing integrated Gal-ER and Gal4 responsive fos genes were transformed in a strictly estrogen-dependent manner. The exogenous fos gene was rapidly induced to maximal levels within 1-2 hr of estrogen addition. Elevated Fos activity in turn stimulated transcription of the endogenous fra-1 gene. These data demonstrate the utility of the Gal-ER induction system as a powerful genetic switch for regulating heterologous genes and, in particular, for identifying Fos targets in mammalian cells. PMID- 8446580 TI - Recombinant kinesin motor domain binds to beta-tubulin and decorates microtubules with a B surface lattice. AB - We have expressed the recombinant squid kinesin head domain in Escherichia coli and studied its interaction with microtubules. The head is active as a microtubule-stimulated ATPase and binds to microtubules, but it does not support microtubule gliding by itself. The head binds to both microtubules and depolymerized tubulin. In each case the zero-length crosslinker 1-ethyl-3-[3 dimethylamino)propyl] carbodiimide induces a bond specifically to beta- but not alpha-tubulin. The head decorates brain microtubules with an 8-nm axial spacing. Thus the stoichiometry is one kinesin head per tubulin dimer. The lattice is that of flagellar B-tubules, implying that reassembled microtubules are not symmetric. Moreover, the A- and B-tubules of intact flagellar outer doublets are both decorated with a B lattice. This suggests that the B lattice is a general property of microtubules. PMID- 8446581 TI - A small single-"finger" peptide from the erythroid transcription factor GATA-1 binds specifically to DNA as a zinc or iron complex. AB - Sequence-specific DNA binding has been demonstrated for a synthetic peptide comprising only one of the two "finger"-like domains of the erythroid transcription factor GATA-1 (also termed Eryf-1, NF-E1, or GF-1). Quantitative analysis of gel-retardation assays yields a specific association constant of 1.2 x 10(8) M, compared with values of about 10(9) M for the full-length natural GATA 1 protein. By the use of peptides of various lengths, it was possible to delineate the smallest region necessary for specific binding. A single C-terminal finger of the double-finger motif is necessary but not sufficient for sequence specific interaction. Basic amino acids located C-terminal to the finger (some more than 20 amino acids away) are also essential for tight binding. In addition to demonstrating that zinc is important for the formation of an active binding complex, we show that other ions, notably Fe2+, can fulfill this role. Our results make it clear that the GATA-1 metal binding motif is quite distinct from that found in the steroid hormone family and that GATA-1 is a member of a separate class of DNA binding proteins. PMID- 8446582 TI - Endoplasmic reticulum-through-Golgi transport assay based on O-glycosylation of native glycophorin in permeabilized erythroleukemia cells: role for Gi3. AB - An assay for endoplasmic reticulum (ER)-through-Golgi transport has been developed in streptolysin O-permeabilized murine erythroleukemia (MEL) cells. The reporter proteins are metabolically labeled native murine glycophorins, which display a distinctive shift in electrophoretic mobility after acquisition of O linked oligosaccharides. The O-linked sugars are acquired at a site distal to a brefeldin A block, presumably in a cis Golgi compartment, and sialylation occurs in middle and/or trans Golgi compartments. In permeabilized cells supplemented with cytosolic proteins and an ATP-generating system, 20-50% of the radiolabeled precursor glycophorins can be converted to the mature, sialylated form. This maturation process is ATP- and cytosol-dependent and is blocked by guanosine 5' [gamma-thio]triphosphate (GTP[gamma S]). Electron microscopy of permeabilized MEL cells shows retention of ER elements, stacked Golgi cisternae, free polysomes, and other subcellular components. In the presence of GTP[gamma S], dilated vesicles accumulate around the Golgi stacks. Antisera to the carboxyl terminus of the Golgi resident alpha subunit of Gi3 inhibit maturation of glycophorin. To our knowledge, a transport assay utilizing O-glycosylation of an endogenous protein as a monitor of ER-through-Golgi traffic in permeabilized cells has not been reported previously. Furthermore, the data provide evidence for heterotrimeric GTP-binding protein involvement in Golgi function. PMID- 8446583 TI - Defective pro alpha 2(I) collagen synthesis in a recessive mutation in mice: a model of human osteogenesis imperfecta. AB - Osteogenesis imperfecta (OI) is a heritable disorder of connective tissue associated with fractures, osteopenia, and short stature. OI results from mutations affecting the pro alpha 1 or pro alpha 2 gene of type I collagen. We describe a strain of mice with a nonlethal recessively inherited mutation (oim) that results in phenotypic and biochemical features that simulate moderate to severe human OI. The phenotype of homozygous oim mice includes skeletal fractures, limb deformities, generalized osteopenia, and small body size. Their femurs are smaller and demonstrate marked cortical thinning and fewer medullary trabeculae than those of wild-type mice. Breeding studies show the mutation is inherited in most crosses as a single recessive gene on chromosome 6, near the murine Cola-2 gene. Biochemical analysis of skin and bone, as well as isolated dermal fibroblast cultures, demonstrate that alpha 1(I) homotrimeric collagen accumulates in these tissues and is secreted by fibroblasts. Short labeling studies in fibroblasts demonstrate an absence of pro alpha 2(I) collagen chains. Nucleotide sequencing of the cDNA encoding the COOH-propeptide reveals a G deletion at pro alpha 2(I) nucleotide 3983; this results in an alteration of the sequence of the last 48 amino acids. The oim mouse will facilitate the study of type I collagen-related skeletal disease. PMID- 8446584 TI - Comparison of variable region 3 sequences of human immunodeficiency virus type 1 from infected children with the RNA and DNA sequences of the virus populations of their mothers. AB - We have compared the variable region 3 sequences from 10 human immunodeficiency virus type 1 (HIV-1)-infected infants to virus sequences from the corresponding mothers. The sequences were derived from DNA of uncultured peripheral blood mononuclear cells (PBMC), DNA of cultured PBMC, and RNA from serum collected at or shortly after delivery. The infected infants, in contrast to the mothers, harbored homogeneous virus populations. Comparison of sequences from the children and clones derived from DNA of the corresponding mothers showed that the transmitted virus represented either a minor or a major virus population of the mother. In contrast to an earlier study, we found no evidence of selection of minor virus variants during transmission. Furthermore, the transmitted virus variant did not show any characteristic molecular features. In some cases the transmitted virus was more related to the virus RNA population of the mother and in other cases it was more related to the virus DNA population. This suggests that either cell-free or cell-associated virus may be transmitted. These data will help AIDS researchers to understand the mechanism of transmission and to plan strategies for prevention of transmission. PMID- 8446585 TI - Gradients of transgene expression directed by the human myoglobin promoter in the developing mouse heart. AB - Prior studies using transient transfection assays in cultured avian and murine skeletal myotubes indicate that the proximal 2-kb segment of the 5' flanking region of the human myoglobin gene contains transcriptional control elements sufficient to direct muscle-specific and developmentally regulated expression of reporter genes. To examine the function of the human myoglobin gene promoter during development of skeletal and cardiac myocytes in the intact animal, a 2.0 kb myoglobin gene upstream fragment was fused to an Escherichia coli lacZ reporter gene and injected into fertilized mouse oocytes. beta-Galactosidase (beta-gal) activity was detected selectively in cardiac and skeletal myocytes of fetal and adult transgenic mice. A distinctive spatial pattern of myoglobin promoter activity was observed in fetal hearts: beta-gal staining was more pronounced within the left ventricular subendocardium than within the subepicardium and was essentially undetectable in the ventricular trabeculae or atria. Expression of endogenous myoglobin mRNA and protein, assessed by in situ hybridization and immunohistochemistry, demonstrated a similar spatial pattern. In contrast, hearts from adult transgenic mice demonstrated essentially homogeneous expression of beta-gal and of endogenous myoglobin mRNA and protein throughout the myocardium, including the trabeculae and atria. These data indicate that the 2.0-kb upstream region of the human myoglobin gene includes cis acting regulatory elements sufficient to direct transgene expression during murine cardiac development that is myocyte-specific and responsive to positional cues in a similar manner to the endogenous myoglobin gene. PMID- 8446586 TI - Successful transient introduction of Leishmania RNA virus into a virally infected and an uninfected strain of Leishmania. AB - Viruses of Leishmania have recently been identified and characterized. These viruses are consistently double-stranded RNA viruses of approximately 5 kb. To date, they have not been reported to exist outside their protozoan host, nor have they been shown to be infectious. We report here the ability to transiently transfer these viruses to two strains of Leishmania, one previously infected and one that did not previously carry a virus. A PCR-based assay was used to detect viral negative-stranded RNA. Input RNA was ruled out as the source of template because a replication-incompetent (UV inactivated) virus was not detectable after transfer into Leishmania. PMID- 8446587 TI - Kindling produces long-lasting and selective changes in gene expression of hippocampal neurons. AB - To test the hypothesis that repeated subconvulsive stimulations required to induce kindling can permanently alter gene expression of hippocampal neurons, we used Northern and in situ hybridization analyses to measure steady-state mRNA levels encoding several phenotypic proteins. mRNA encoding a membrane-bound protein, ligatin, was significantly reduced in kindled brains relative to naive and sham control animals. This change in gene expression persisted for over 4 months after kindling, was associated with a decrease in ligatin protein expression, was not produced by single or multiple seizures that did not induce the kindling phenomena, and was blocked by MK801. These results provide direct evidence that kindling can cause persistent changes in the expression of specific genes in hippocampal neurons and suggest that N-methyl-D-aspartate receptor activated changes in gene expression may be a basic molecular mechanism underlying some of the long-lasting plasticity changes seen in kindling or models of long-term memory. PMID- 8446588 TI - Adipose pyruvate carboxylase: amino acid sequence and domain structure deduced from cDNA sequencing. AB - The complete amino acid sequence of 3T3-L1 adipocyte pyruvate carboxylase (PC) [pyruvate:carbon-dioxide ligase (ADP-forming), EC 6.4.1.1] has been deduced from sequencing overlapping cDNA clones obtained from an adipocyte cDNA library constructed in the lambda Zap vector. The encoding mRNA for PC promoter contains 4067 nt, including a 3534-nt coding sequence and noncoding regions of 100 and 433 nt at the 5' and 3' ends, respectively. The biotinylated lysine of the encoded PC promoter (1178 amino acids with a calculated M(r) of apocarboxylase = 129,784) is located 35 residues from the COOH-terminal end and, as in most other biotin enzymes, is in the consensus sequence AMKM. The adipocyte PC is closely similar (53% identity) to the yeast enzyme and contains different segments that are homologous with regions from the biotin carboxylase component of Escherichia coli acetyl-CoA carboxylase, the keto acid-binding subunits of Propionibacterium shermanii oxaloacetate transcarboxylase and Klebsiella pneumoniae oxaloacetate decarboxylase, and to the biotin carboxyl-carrier protein of the bacterial biotin enzymes. In addition to the putative mitochondrial targeting signal, functional domains are readily identifiable in the sequence and are in the following order: biotin carboxylase-carboxyltransferase-biotin carboxyl-carrier protein, as proposed for yeast PC. PMID- 8446589 TI - Gamma-tocopherol detoxification of nitrogen dioxide: superiority to alpha tocopherol. AB - In the vitamin E group, alpha-tocopherol is generally considered to be the most potent antioxidant with the highest vitamin bioactivity, yet gamma-tocopherol is produced in greater amounts by many plants and is the principal tocopherol in the United States diet. This report describes a fundamental difference in the chemical reactivities of alpha-tocopherol and gamma-tocopherol with nitrogen dioxide (NO2), which leads to the formation of a nitrosating agent from alpha tocopherol, but not from gamma-tocopherol. Nitric oxide (NO) is a major product of the reaction of gamma-tocopherol with NO2, while alpha-tocopherol reacts with NO2 to form an intermediate tocopheroxide analogue. The biological significance of gamma-tocopherol is suggested by limited epidemiological data as well as the observation that it is a more potent inhibitor than alpha-tocopherol of neoplastic transformation during the postinitiation phase in 3-methylcholanthrene treated C3H/10T1/2 murine fibroblasts. This latter property suggests the superiority of gamma-tocopherol in a mammalian biological assay and a role for endogenous NO production in promotion of neoplastic transformation. PMID- 8446590 TI - Molten-globule conformation of Arc repressor monomers determined by high-pressure 1H NMR spectroscopy. AB - The conformation of the pressure-dissociated monomer of Arc repressor was characterized by 1H NMR spectroscopy. The NMR spectra of the monomer under pressure (up to 5.0 kbar; 1 bar = 100 kPa) are typical of a molten globule and they are considerably different from those of the native dimer and thermally denatured monomer. The two-dimensional nuclear Overhauser effect spectra suggest that the pressure-induced molten globule retains some secondary structure. The presence of nuclear Overhauser effects in the beta-sheet region in the dissociated state suggests that the intermonomer beta-sheet (residues 8-14) in the native dimer is replaced by an intramonomer beta-sheet. Changes in one dimensional and two-dimensional NMR spectra prior to pressure dissociation were found and suggest the existence of a "predissociated" state. PMID- 8446591 TI - Glucose sensing in pancreatic islet beta cells: the key role of glucokinase and the glycolytic intermediates. AB - The beta cells of the pancreatic islets of Langerhans respond to changes in glucose concentration by varying the rate of insulin synthesis and secretion. Beta cells sense glucose concentration by the levels of the products of glucose catabolism. Distinctive beta-cell proteins glucose transporter 2 and glucokinase catalyze the first two steps in beta-cell glucose catabolism. To test whether either protein controls the sensitivity of the beta cell to glucose by controlling the rate of glucose catabolism, we used gene-transfer techniques to express the isoenzymes glucose transporter 1 and hexokinase I in beta cells and measured the response to glucose of the insulin gene promoter. Cells expressing glucose transporter 1 do not differ significantly from control cells, but in cells expressing hexokinase I, insulin promoter activity increases, reaches a maximum by 1 mM glucose, and does not respond to changes in glucose concentration within the physiologic range. We conclude that glucokinase catalyzes the rate limiting step of glucose catabolism in beta cells and, therefore, acts as the glucose sensor. Pyruvate, the end product of anaerobic glycolysis, is readily oxidized by mitochondria in normal beta cells but cannot substitute for glucose as a stimulator of insulin synthesis and secretion. We found that pyruvate can stimulate the insulin promoter in cells expressing the bacterial gluconeogenic enzyme phosphoenolpyruvate carboxykinase, which allows the conversion of pyruvate to phosphoenolpyruvate and the earlier intermediates of glycolysis. We conclude that the intermediates of anaerobic glycolysis between fructose 1,6-diphosphate and phosphoenolpyruvate are essential for beta-cell glucose sensing. PMID- 8446592 TI - Isolation of proteins associated with kinetoplast DNA networks in vivo. AB - Kinetoplast DNA (kDNA), the mitochondrial DNA of trypanosomes, is a highly condensed disc-shaped network of catenated DNA circles consisting of maxicircles, the equivalent of conventional mitochondrial DNA, and several thousand smaller circular DNAs termed minicircles. Upon cell lysis, kDNA expands, giving rise to a two-dimensional network of catenated circles with an overall diameter close to that of the whole cell. To identify proteins associated with the condensed form of kDNA in the cell, proteins were reversibly crosslinked to kDNA in whole cells of Crithidia fasciculata by formaldehyde treatment. Crosslinked networks were purified and found to retain a condensed structure which becomes fully expanded upon proteinase K treatment or reversal of the crosslinks by heating at 65 degrees C. Five low molecular weight proteins released from the kDNA by heat treatment were purified by polyacrylamide gel electrophoresis and their amino terminal sequences were determined. PCR amplification and sequence analysis of cDNA sequences between these amino-terminal sequences and the miniexon (spliced leader) sequence present at the 5' end of all C. fasciculata mRNAs predicts the presence of 9-amino acid presequences with features characteristic of mitochondrial presequences on three of the proteins. Two of these proteins are lysine-rich basic proteins. These findings suggest that basic proteins may play a role in the condensation of kDNA in the kinetoplast and that these proteins are imported into the kinetoplast by a mechanism involving a cleavable presequence. PMID- 8446593 TI - Functionally distinct roles for glycosylation of alpha and beta integrin chains in cell-matrix interactions. AB - Laminin interaction with gp120/140, a B16-F10 laminin-binding protein immunologically related to alpha 6 beta 1 integrin, has been shown to be dependent on oligosaccharides from both ligand and receptor. Lectin analysis of gp120/140 led to the conclusion that this integrin is a sialoglycoprotein bearing mainly complex antennary structures. By means of exoglycosidase treatment, it was possible to identify alpha-galactosyl residues on the integrin alpha chain as the laminin-binding determinants. These residues are involved in cell adhesion to laminin. On the other hand, beta-chain complex antennary structures, whose synthesis could be inhibited by swainsonine, were associated with cell spreading rather than cell adhesion. Thus, it was possible to modulate integrin-mediated cell adhesion and spreading through changes in the glycosylation state of integrin alpha and beta chains. PMID- 8446594 TI - Interleukin 1 beta (IL-1 beta) processing in murine macrophages requires a structurally conserved homologue of human IL-1 beta converting enzyme. AB - Murine interleukin 1 beta (IL-1 beta) convertase (mICE) was identified in cytosolic extracts of peritoneal exudate cells (PECs) and macrophage cell lines. mICE cleaves both the human and mouse IL-1 beta precursors (pIL-1 beta) at sites 1 and 2 but fails to cleave a human pIL-1 beta (Asp116 to Ala) mutant at site 2, indicating that Asp is required to the left of the scissile bond. Ac-Tyr-Val-Ala Asp-amino-4-methyl coumarin, patterned after site 2 of human pIL-1 beta, is a fluorogenic substrate for mICE, while the tetrapeptide aldehyde Ac-Tyr-Val-Ala Asp-CHO is a potent inhibitor (Ki = 3 nM) that prevents generation and release of mature IL-1 beta by PECs (IC50 = 7 microM). Cloning of a full-length 1.4-kb cDNA shows that mICE is encoded as a 402-aa proenzyme (p45) that can be divided into a prodomain (Met1-Asp122), followed by a p20 subunit (Gly123-Asp296), a connecting peptide (Ser297-Asp314), and a p10 subunit (Gly315-His402). At the amino acid level, p45, p20, and p10 are 62%, 60%, and 81% identical with human IL-1 beta convertase (hICE). The active site Cys284 lies within a completely conserved stretch of 18 residues; however, Ser289 in hICE, which aligns with the catalytic region of serine and viral cysteinyl proteases, is absent from mICE. Expression in Escherichia coli of a truncated cDNA encoding Asn119-His402 generated active enzyme, which was autocatalytically processed at three internal Asp-Xaa bonds to generate a p20 subunit (Asn119-Asp296) complexed with either p11 (Ala309-His402) or p10. Recombinant mICE cleaves murine pIL-1 beta accurately at the Asp117 Val118 bond. The striking similarities of the human and murine enzymes will make it possible to assess the therapeutic potential of hICE inhibitors in murine models of disease. PMID- 8446595 TI - Hirudin as a molecular probe for thrombin in vitro and during systemic coagulation in the pig. AB - The amount of thrombin active in vivo in the intravascular space (blood and endothelial surface), both basally and in experimental intravascular coagulation, is measured by way of the accessibility of thrombin to intravascular hirudin. Blood samples from pigs given intravenous 125I-labeled hirudin contain 125I labeled hirudin-thrombin complex in concentrations indicative of a basal thrombin concentration in vivo of 0.5 nmol/liter. Intravenous infusion of Salmonella endotoxin elicits an increase in the circulating concentration of hirudin thrombin complex that begins within 15 min and is 20-30 times basal after 4 hr. Induction of mild intravascular coagulation is evidenced by a modest reduction in plasma fibrinogen concentrations. It is concluded that there is a basal pool of hirudin-accessible thrombin in the intravascular space that, were it free in the plasma phase, would be sufficient in principle to sustain intravascular coagulation. PMID- 8446596 TI - Cancer dormancy: isolation and characterization of dormant lymphoma cells. AB - "Tumor dormancy" is an operational term used to describe a prolonged quiescent state in which tumor cells are present, but tumor progression is not clinically apparent. Although clinical examples of tumor dormancy abound, little is known regarding the mechanisms underlying this state. Here we utilize an antibody induced dormancy model of an aggressive murine B-cell lymphoma (BCL1) and show that the induction of the dormant state is accompanied by dramatic changes in tumor cell morphology and cell cycle status. These data indicate the feasibility of altering the malignant phenotype of transformed cells by specific signals originating at the cell surface, and they suggest new opportunities for therapeutic intervention in cancer. PMID- 8446597 TI - Three inhibitors of type 1 human immunodeficiency virus long terminal repeat directed gene expression and virus replication. AB - Transcription of type 1 human immunodeficiency virus (HIV-1) provirus is governed by the viral long terminal repeat (LTR). Drugs can block HIV-1 replication by inhibiting activity of its LTR. We report that topotecan, beta-lapachone, and curcumin are potent and selective inhibitors of HIV-1 LTR-directed gene expression, at concentrations that have minor effects on cells. At these concentrations, each drug inhibited p24 antigen production in cells either acutely or chronically infected with HIV-1. Their target is transcriptional function of the LTR. PMID- 8446598 TI - Stromelysin 3 belongs to a subgroup of proteinases expressed in breast carcinoma fibroblastic cells and possibly implicated in tumor progression. AB - The expression of the stromelysin 3 (ST3) gene, which encodes a putative matrix metalloproteinase, was studied during breast cancer progression. The ST3 gene is expressed in all invasive breast carcinomas, in a number of their metastases, and in some in situ carcinomas where the probability of detecting ST3 transcripts correlates with the known risk of these carcinomas to become invasive. ST3 RNA and protein were specifically detected in fibroblastic cells immediately surrounding the neoplastic cells in both primary and metastatic tumors. This expression pattern distinguishes the ST3 gene from other matrix metalloproteinase genes, most notably from the 72-kDa type IV collagenase gene, which can be expressed in fibroblastic cells distributed throughout the stroma of primary breast carcinomas. Furthermore, high levels of 72-kDa type IV collagenase, but not of ST3 transcripts, are detected in benign breast fibroadenomas. Interestingly, the urokinase and ST3 genes exhibit very similar patterns of expression in breast carcinomas, which suggests that their products may cooperate during cancer progression. PMID- 8446599 TI - Roles of Ser101, Asp236, and His237 in catalysis of thioesterase II and of the C terminal region of the enzyme in its interaction with fatty acid synthase. AB - Thioesterase II (TE II), present in specialized tissues, catalyzes the chain termination and release of medium-chain fatty acids from fatty acid synthase [FAS; acyl-CoA:malonyl-CoA C-acyltransferase (decarboxylating, oxoacyl- and enoyl reducing and thioester-hydrolyzing), EC 2.3.1.85]. We have expressed rat mammary gland TE II in Escherichia coli and created several site-directed mutants. Replacing both Ser101 and His237 with Ala yielded inactive proteins, suggesting that these residues are part of the catalytic triad as in FAS thioesterase (TE I). Mutating the conserved Asp236 or modifying it with Woodward's reagent K caused partial loss (40%) of TE II activity and reduced reactivity of Ser101 and His237 toward their specific inhibitors, phenylmethylsulfonyl fluoride and diethylpyrocarbonate, respectively. These results suggested that Asp236 enhances, but is not essential for, the reactivity of Ser101 and His237. Mutation analyses revealed that, at the C terminus, Leu262 is critical for TE II to interact with FAS. Hydrophobic interactions seem to play a role, since the interaction of TE II with FAS is enhanced by polyethylene glycol but reduced by salt. The Ser101 and His237 mutants and a synthetic C-terminal decapeptide did not compete in the interaction. These results suggest that a TE II-acyl FAS complex forms first, which then is stabilized by the interaction of the hydrophobic C terminus of TE II with FAS, leading ultimately to hydrolysis and release of fatty acid. PMID- 8446600 TI - Maturation of thylakoid lumen proteins proceeds post-translationally through an intermediate in vivo. AB - Many thylakoid lumen proteins are synthesized outside the chloroplast as larger molecular weight precursors and then processed to their mature size during transport to the lumenal space. We have examined the post-translational processing of thylakoid lumen proteins in vivo by pulse-radiolabeling experiments with Chlamydomonas reinhardtii. Antibodies against the lumenal protein cytochrome c6 specifically immunoprecipitated three polypeptides from extracts of briefly pulse-radiolabeled cells. The molecular weights and kinetics of synthesis and turnover indicate that these three polypeptides are (i) the full-length cytochrome c6 precursor, (ii) a partially processed precursor (intermediate), and (iii) the completely processed mature protein. Identification of analogous forms of two other lumenal proteins, plastocyanin and the oxygen evolving enhancer 1 protein, indicates that the maturation of thylakoid lumen proteins occurs post translationally in vivo and that the partially processed intermediate is a general feature of the pathway. The intermediate form of cytochrome c6 accumulated to a greater extent in cells incubated at 10 degrees C, relative to cells incubated at 22 degrees C, concomitantly with a decrease in the accumulation of the mature protein. The intermediate accumulating at 10 degrees C is quantitatively converted to the mature protein upon incubation at higher temperature, thus demonstrating a precursor-product relationship between the intermediate and mature forms of cytochrome c6. Our results prove the model [Smeekens, S., Bauerle, C., Hageman, J., Keegstra, K. & Weisbeek, P. (1986) Cell 46, 365-375] that precursors of lumenal proteins are post-translationally converted to their mature forms in two steps through a distinct intermediate. PMID- 8446601 TI - The emergence of new DNA repeats and the divergence of primates. AB - We have identified four genetic novelties that are fixed in specific primate lineages and hence can serve as phylogenetic time markers. One Alu DNA repeat is present in the human lineage but is absent from the great apes. Another Alu DNA repeat is present in the gorilla lineage but is absent from the human, chimpanzee, and orangutan. A progenitor Xba1 element is present in the human, chimpanzee, gorilla, and orangutan, but only in the human lineage did it give rise to a transposed progeny, Xba2. The saltatory appearance of Xba2 is an example of a one-time event in the evolutionary history of a species. The enolase pseudogene, known to be present as a single copy in the human, was found to be present in four other primates, including the baboon, an Old World monkey. Using the accepted value of 5 x 10(-9) nucleotide substitutions per site per year as the evolutionary rate for pseudogenes, we calculated that the enolase pseudogene arose approximately 14 million years ago. The calculated age for this pseudogene and its presence in the baboon are incongruent with each other, since Old World monkeys are considered to have diverged from the hominid lineage some 30 million years ago. Thus the rate of evolution in the enolase pseudogene is only about 2.5 x 10(-9) substitutions per site per year, or half the rate in other pseudogenes. It is concluded that rates of substitution vary between species, even for similar DNA elements such as pseudogenes. We submit that new DNA repeats arise in the genomes of species in irreversible and punctuated events and hence can be used as molecular time markers to decipher phylogenies. PMID- 8446602 TI - Genetic analysis of diabetes and insulitis in an interspecific cross of the nonobese diabetic mouse with Mus spretus. AB - The nonobese diabetic (NOD) mouse is a widely used model for genetic studies of insulin-dependent diabetes mellitus due to the similarities between the murine and human diseases. To aid in the localization and identification of diabetes related susceptibility genes, we have constructed an interspecific backcross between NOD and Mus spretus (SEG/Pas) mice. Although no diabetic animals were observed in the first backcross generation of (SEG/Pas x NOD) x NOD (BC1), the incidence of insulitis (lymphocyte infiltration of the islets of Langerhans) exceeded 20% after injections of cyclophosphamide, a treatment that provokes an acute form of diabetes in NOD mice. Insulitis, a prediabetic condition, is a useful phenotype in studies of diabetes susceptibility. In the second backcross (BC2) generation, 8% of the animals became diabetic and 76% were found to have insulitis. Genetic mapping studies in the BC2 families confirmed the importance of the major histocompatibility complex region on the severity of insulitis and suggested that additional susceptibility loci were linked to markers on mouse chromosomes 3, 6, and 15. Mus spretus crosses have been an important tool in recent advances in murine genetics, and our results extend their usefulness to the study of a multifactorial disease. PMID- 8446603 TI - Enhanced immunity to human immunodeficiency virus (HIV) envelope elicited by a combined vaccine regimen consisting of priming with a vaccinia recombinant expressing HIV envelope and boosting with gp160 protein. AB - Transmission studies have suggested that an optimal human immunodeficiency virus type 1 (HIV-1) vaccine should induce both neutralizing antibodies and cytolytic T cells to eliminate free virus and infected cells. A phase I trial in healthy HIV 1-seronegative persons was conducted with a combination HIV-1 vaccine regimen (strain IIIB) consisting of priming with a recombinant vaccinia (vac/env) virus expressing HIV-1 envelope and boosting with a gp160 glycoprotein derived from a recombinant baculovirus (rgp160). T-cell and antibody responses detected after immunization with either vac/env alone or rgp160 alone were generally of low magnitude and transient, and no subject developed neutralizing antibodies. In contrast, recipients of the combination regimen demonstrated in vitro T-cell proliferative responses to homologous HIV-1 antigens that were 3- to 10-fold higher than responses with either vaccine alone, and these responses were sustained for > 18 months in 75% of recipients. Moreover, both CD8+ and CD4+ cytolytic T cells were detected. Antibody responses (titer, 1:800 to 1:102,400) to homologous HIV envelope developed in all recipients of the combination regimen, and neutralizing antibodies were detected in 7 of 13. Thus, immunization with a live virus vaccine followed by boosting with a soluble protein offers promise for inducing the broad immunity needed in an HIV vaccine. PMID- 8446604 TI - Immunoglobulin D-deficient mice can mount normal immune responses to thymus independent and -dependent antigens. AB - To examine the in vivo function of IgD we generated mice deficient for IgD by gene targeting. The IgD-mice show a reduced B-cell compartment with 30-50% less B cells in the spleen and lymph nodes but show a normal pre-B-cell compartment. The surface-IgD- B cells express two to three times more surface IgM than B cells of control animals. Serum concentrations of the immunoglobulin isotypes of IgD- mice are almost normal, indicating that surface-IgD expression is not necessary for class switching of B cells. Immunization experiments showed that IgD- mice could respond well to thymus-dependent and -independent antigens. After immunization normal germinal centers developed in the IgD- mice. These data suggest that IgD is not necessary for the induction of immune responses but may be important in homeostasis of cells in the B-cell compartment. PMID- 8446605 TI - Kinship bioassay on hypervariable loci in blacks and Caucasians. AB - Four hypervariable loci were examined in DNA samples of American Blacks and Caucasians. Genetic diversity, measured by mean kinship within race, is 0.004 for a sliding window equal to twice the radius of coalescence of the autoradiographic bands. Kinship increases with the width of a window or bin, but it is an order of magnitude less than for blood groups and isozymes. This must reflect the greater mutability of hypervariable loci and absence of divergent selection. Low kinship implies that matching probabilities do not depend critically on race. Complete matching between pairs of loci shows deviations from independence, presumably because of inadvertent inclusion of replicated samples or related individuals. Multilocus matching probabilities were corrected for this (possibly spurious) dependence; the correction is negligible. When the complexities of coalescence, kinship, and dependent matching are allowed for, the probability calculations used in forensic identification are reliable. Recent counterarguments without theoretical basis or empirical support are discussed. PMID- 8446606 TI - Cloning and expression of the gene from Candida albicans that encodes a high affinity corticosteroid-binding protein. AB - We have previously demonstrated the presence of a corticosteroid-binding protein (CBP) in Candida albicans and speculated on its homology to the glucocorticoid receptor. To explore this relationship further, we cloned the CBP gene. Our strategy employed sequencing enzymatically derived peptide fragments from purified CBP and using this information to synthesize degenerate oligonucleotide primers for use in the PCR. A 117-bp fragment amplified from C. albicans DNA was then used to screen a genomic library. Hybridizing clones were isolated, and DNA sequencing revealed an open reading frame of 1467 bp which encoded a protein with a molecular weight of 55,545. Southern analysis demonstrated that the gene was present at a unique locus within chromosome R of the Candida genome, while Northern analysis showed that the gene was expressed in C. albicans as a 1.8-kb transcript. CBP was over-expressed in Saccharomyces cerevisiae, and it exhibited an apparent dissociation constant (Kd) of 7 nM for [3H]corticosterone and displayed a steroid hormone binding profile comparable to that of the native protein. Searches of the data banks revealed little overall similarity to other cloned genes. However, the amino acid sequence contains a dinucleotide-binding fingerprint. In conclusion, we have cloned the gene encoding the CBP from C. albicans and have shown that the expressed protein has the properties of the native CBP. A comparison of the cloned gene to members of the steroid-thyroid retinoic acid receptor gene superfamily showed that CBP is unrelated to these hormone receptors. PMID- 8446607 TI - Regulatory arrestin cycle secures the fidelity and maintenance of the fly photoreceptor cell. AB - Excitation of fly photoreceptor cells is initiated by photoisomerization of rhodopsin to the active form of metarhodopsin. Fly metarhodopsin is thermostable, does not bleach, and does not regenerate spontaneously to rhodopsin. For this reason, the activity of metarhodopsin must be stopped by an effective termination reaction. On the other hand, there is also a need to restore the inactivated photopigment to an excitable state in order to keep a sufficient number of photopigment molecules available for excitation. The following findings reveal how these demands are met. The photopigment undergoes rapid phosphorylation upon photoconversion of rhodopsin to metarhodopsin and an efficient Ca2+ dependent dephosphorylation upon regeneration of metarhodopsin to rhodopsin. Phosphorylation decreases the ability of metarhodopsin to activate the guanine nucleotide-binding protein. Binding of 49-kDa arrestin further quenches the activity of metarhodopsin and protects it from dephosphorylation. Light-dependent binding and release of 49-kDa arrestin from metarhodopsin- and rhodopsin containing membranes, respectively, directs the dephosphorylation reaction toward rhodopsin. This ensures the return of phosphorylated metarhodopsin to the rhodopsin pool without initiating transduction in the dark. Assays of rhodopsin dephosphorylation in the Drosophila retinal degeneration C (rdgC) mutant, a mutant in a gene previously cloned and predicted to encode a serine/threonine protein phosphatase, reveal that phosphorylated rhodopsin is a major substrate for the rdgC phosphatase. We propose that mutations resulting in either a decrease or an improper regulation of rhodopsin phosphatase activity bring about degeneration of the fly photoreceptor cells. PMID- 8446608 TI - Expression of insulin-like growth factor I gene in osmoregulatory organs during seawater adaptation of the salmonid fish: possible mode of osmoregulatory action of growth hormone. AB - Growth hormone has been shown to contribute to seawater adaptation of salmonid fishes. The growth influence of growth hormone is mediated largely by hepatic production of insulin-like growth factor I (IGF-I). To study the growth hormone IGF-I axis in osmoregulation, we measured IGF-I mRNA in the liver, gill, and body kidney from rainbow trout by Northern analysis. The levels of IGF-I mRNA in all tissues increased significantly after injection of growth hormone. Transfer of trout from fresh water to 80% seawater evoked an increase in plasma growth hormone after 1 day. IGF-I mRNA was not altered significantly in the liver, but it was increased in the gill and body kidney after 1 and 8 days, respectively. These observations indicate that the IGF-I gene is expressed differently among these organs during seawater adaptation. Growth hormone may stimulate hypoosmoregulatory ability by inducing local expression of IGF-I in osmoregulatory organs, although the possibility that IGF-I expression might occur in part independently of growth hormone during seawater adaptation cannot be excluded. PMID- 8446609 TI - Elongation factor SII-dependent transcription by RNA polymerase II through a sequence-specific DNA-binding protein. AB - In eukaryotes the genetic material is contained within a coiled, protein-coated structure known as chromatin. RNA polymerases must recognize specific nucleoprotein assemblies and maintain contact with the underlying DNA duplex for many thousands of base pairs. Template-bound lac operon repressor from Escherichia coli arrests RNA polymerase II in vitro and in vivo [Kuhn, A., Bartsch, I. & Grummt, I. (1990) Nature (London) 344, 559-562; Deuschele, U., Hipskind, R. A. & Bujard, H. (1990) Science 248, 480-483]. We show that in a reconstituted transcription system, elongation factor SII enables RNA polymerase II to proceed through this blockage at high efficiency. lac repressor-arrested elongation complexes display an SII-activated transcript cleavage reaction, an activity associated with transcriptional read-through of a previously characterized region of bent DNA. This demonstrates factor-dependent transcription by RNA polymerase II through a sequence-specific DNA-binding protein. Nascent transcript cleavage may be a general mechanism by which RNA polymerase II can bypass many transcriptional impediments. PMID- 8446610 TI - Development of potent gastrin-releasing peptide antagonists having a D-Pro psi(CH2NH)-Phe-NH2 C terminus. AB - Gastrin-releasing peptide (GRP) is a 27-amino acid neuroendocrine hormone that may play a role in the pathophysiology of small cell lung carcinoma. GRP and bombesin, a structurally related peptide, stimulate the growth of some cultured cell types. C-terminal GRP peptide analogs were developed that inhibited 6 nM bombesin-induced [3H]thymidine incorporation into quiescent murine Swiss 3T3 cells, which routinely produced a 6-fold stimulation over the basal extent of incorporation. The peptides were also analyzed for their capacity to inhibit the binding of 50 pM 125I-labeled GRP to Swiss 3T3 cells. The combination of two chemical modifications, each antagonistic in itself, led to the creation of antagonists with orders of magnitude greater potency than either modification alone. (i) Antagonist analogs of the form -Leu26-psi(CH2NH)-Xaa27-NH2 [where Xaa is Leu, norleucine (Nle), or Phe; residues numbered after GRP], similar to those introduced by Coy and coworkers [for review, see Jensen, R. T. & Coy, D. H. (1991) Trends Pharmacol. Sci. 12, 13-19], were found to have nanomolar potencies. (ii) We found that an octapeptide C-terminal GRP analog having D-Pro adjacent to the C-terminal amino acid amide was antagonistic, with a potency of 40 nM. By combining both modifications, specific analogs were found with potencies > 1000 fold greater than our lead structure--[(4'-hydroxy)-3-phenylpropanoyl]-Pro-Arg Gly-Asn-His-Tr p-Ala-Val - Gly-His-Leu-psi(CH2NH)-Nle-NH2--and greater than any antagonist previously reported. The analogs [(4'-hydroxy)-3-phenylpropanoyl]-His Trp-Ala-Val-D-Ala-His-D-Pro- psi(CH2NH)-Phe-NH2 and 1-naphthoyl-His-Trp-Ala-Val-D Ala-His-D-Pro-psi(CH2NH)-Phe-NH2 antagonized [3H]thymidine incorporation with IC50 values of approximately 0.3 nM and inhibited the binding of 125I-labeled GRP with IC50 values of approximately 1 pM. These peptides may be of use in the study of the physiology of GRP. PMID- 8446611 TI - Mass spectrometric and Edman sequencing of lipocortin I isolated by two dimensional SDS/PAGE of human melanoma lysates. AB - We have integrated preparative two-dimensional polyacrylamide gel electrophoresis with high-performance tandem mass spectrometry and Edman degradation. By using this approach, we have isolated and identified, by partial sequencing, a human melanoma protein (34 kDa, pI 6.4) as lipocortin I. To our knowledge, this protein was not previously known to be associated with melanoma cells. The identity of the protein was confirmed by two-dimensional immunoblot analysis. High-energy collision-induced dissociation analysis revealed the sequence and acetylation of the N-terminal tryptic peptide and an acrylamide-modified cysteine in another tryptic peptide. Thus, knowledge concerning both the primary structure and covalent modifications of proteins isolated from two-dimensional gels can be obtained directly by this approach, which is applicable to a broad range of biological problems. PMID- 8446612 TI - Glucokinase mutations associated with non-insulin-dependent (type 2) diabetes mellitus have decreased enzymatic activity: implications for structure/function relationships. AB - The glycolytic enzyme glucokinase plays an important role in the regulation of insulin secretion and recent studies have shown that mutations in the human glucokinase gene are a common cause of an autosomal dominant form of non-insulin dependent (type 2) diabetes mellitus (NIDDM) that has an onset often during childhood. The majority of the mutations that have been identified are missense mutations that result in the synthesis of a glucokinase molecule with an altered amino acid sequence. To characterize the effect of these mutations on the catalytic properties of human beta-cell glucokinase, we have expressed native and mutant forms of this protein in Escherichia coli. All of the missense mutations show changes in enzyme activity including a decrease in Vmax and/or increase in Km for glucose. Using a model for the three-dimensional structure of human glucokinase based on the crystal structure of the related enzyme yeast hexokinase B, the mutations map primarily to two regions of the protein. One group of mutations is located in the active site cleft separating the two domains of the enzyme as well as in surface loops leading into this cleft. These mutations usually result in large reductions in enzyme activity. The second group of mutations is located far from the active site in a region that is predicted to undergo a substrate-induced conformational change that results in closure of the active site cleft. These mutations show a small approximately 2-fold reduction in Vmax and a 5- to 10-fold increase in Km for glucose. The characterization of mutations in glucokinase that are associated with a distinct and readily recognizable form of NIDDM has led to the identification of key amino acids involved in glucokinase catalysis and localized functionally important regions of the glucokinase molecule. PMID- 8446613 TI - Immunocytochemical analysis of the coiled body in the cell cycle and during cell proliferation. AB - Coiled bodies (CBs) are small, round structures found in the nucleoplasm of most eukaryotic cells. Human autoantibodies to a 80-kDa protein, p80-coilin, are immunohistologic markers for CBs. A polyclonal rabbit antiserum (R288) raised against recombinant p80-coilin was shown to have similar immunochemical properties as human autoantibodies and was used to analyze the expression of p80 coilin-associated CBs in cell cultures synchronized by double thymidine block, nocodazole arrest, serum starvation, or hormonal deprivation. By employing thymidine block and nocodazole arrest of HeLa cells, CBs were observed in immunofluorescent studies to be largest in size in the S and G2 phases of the cell cycle. These large CBs might have coalesced into one or two such structures per cell from smaller and more numerous CBs of three to eight per cell during the mid G1 phase of the cell cycle. No CB-like structures were observed in mitosis and early G1. However, immunoblotting analyses showed that the total amount of p80-coilin remained approximately the same throughout the cell cycle. When HeLa cells were separated into soluble and particulate fractions, p80-coilin was detected predominantly in the soluble fraction in mitosis and early G1, whereas it was present predominantly in the particulate fraction in late G1, S, and G2 when structurally distinct CBs were observed. In the analysis of CBs in two experimental models of cell proliferation (reversal of 3T3 serum starvation and FRTL-5 thyrotropin deprivation), proliferating cells contained larger, brighter, and more numerous CBs as well as a > 2-fold increase in the total amount of p80 coilin compared to that in quiescent cells. The expression of p80-coilin in quiescent cells induced to proliferate and the cyclic formation and breakdown of CBs might be consistent with the notion that CBs may be specialized centers related to the maturation of mRNA, but this evidence is indirect and needs further definitive study. PMID- 8446614 TI - Developmental expression of the platelet-derived growth factor alpha-receptor gene in mammalian central nervous system. AB - We recently reported that the platelet-derived growth factor (PDGF) A-chain gene is highly expressed in neurons of embryonic and adult mouse central nervous system and suggested that its secretion by neurons may support development and maintenance of glia. We have now analyzed the levels and sites of expression of the cognate PDGF alpha-receptor gene in brain and spinal cord of embryonic and adult mice by in situ hybridization. The predominant cell populations in both gray and white matter expressing transcripts of the PDGF alpha-receptor gene are glial cells or their precursors. Transcripts consistently were not detected in neurons. Expression of the PDGF alpha-receptor gene was first observed at embryonic day 15, increased through postnatal day 14, and fell to lower levels in adults. Expression of the alpha-receptor gene corresponds in temporal sequence to the developmental period of glial migration and proliferation and to the expression of PDGF A by neurons. The results indicate that glia but not neurons have the potential to respond to PDGF A and suggest that neurons influence glial cell development through paracrine regulation. PMID- 8446615 TI - Recently recovered Kenyapithecus mandible and its implications for great ape and human origins. AB - We report here a Kenyapithecus africanus juvenile mandible recovered from middle Miocene (ca. 14-16 million years) deposits of Maboko Island (Lake Victoria), Kenya. Symphyseal and dental attributes of the mandible distinguish K. africanus, a species widely regarded as the earliest known member of the great ape and human clade, from other Miocene large-bodied hominoids. The Maboko Island mandible exhibits a markedly proclined symphyseal axis, massive inferior transverse torus, mesiodistally narrow, high-crowned, and strongly procumbent lateral incisor, and molars with cingula restricted to the median buccal cleft. Although the presence of some of these conditions in Kenyapithecus was suggested earlier, the fragmentary and ill-preserved nature of previously known specimens led certain authorities to doubt their validity. Our assessment of mandibular and dental morphology indicates that K. africanus diverged after Proconsul and Griphopithecus but prior to the last common ancestor of Sivapithecus, extant great apes, and humans. The robustly constructed mandibular symphysis and anterior dentition suggest that incisal biting played as important a role as thick molar enamel in the dietary adaptations of K. africanus. PMID- 8446616 TI - A major histocompatibility complex-linked locus in the rat critically influences resistance to diethylnitrosamine carcinogenesis. AB - Major histocompatibility complex (MHC)-linked deletions in the rat are associated with defects in growth and development and increased susceptibility to chemical carcinogens. The present study maps a locus critical for determining susceptibility to diethylnitrosamine (DEN) carcinogenesis by using two groups of MHC-recombinant rats congenic for the MHC and its linked region. Resistance to DEN segregates with a locus (rcc+) that maps between RT1.E and ft, and its homozygous loss markedly increases susceptibility to DEN. Non-MHC genes do not significantly influence the susceptibility of these strains to DEN. The existence of the rcc locus adds support to our hypothesis that some genes in the MHC-linked region play a major role in both normal and abnormal growth. PMID- 8446617 TI - Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. AB - Apolipoprotein E is immunochemically localized to the senile plaques, vascular amyloid, and neurofibrillary tangles of Alzheimer disease. In vitro, apolipoprotein E in cerebrospinal fluid binds to synthetic beta A4 peptide (the primary constituent of the senile plaque) with high avidity. Amino acids 12-28 of the beta A4 peptide are required. The gene for apolipoprotein E is located on chromosome 19q13.2, within the region previously associated with linkage of late onset familial Alzheimer disease. Analysis of apolipoprotein E alleles in Alzheimer disease and controls demonstrated that there was a highly significant association of apolipoprotein E type 4 allele (APOE-epsilon 4) and late-onset familial Alzheimer disease. The allele frequency of the APOE-epsilon 4 in 30 random affected patients, each from a different Alzheimer disease family, was 0.50 +/- 0.06; the allele frequency of APOE-epsilon 4 in 91 age-matched unrelated controls was 0.16 +/- 0.03 (Z = 2.44, P = 0.014). A functional role of the apolipoprotein E-E4 isoform in the pathogenesis of late-onset familial Alzheimer disease is suggested. PMID- 8446618 TI - Photoreceptor differentiation of isolated retinal precursor cells includes the capacity for photomechanical responses. AB - Isolated retinal precursor cells, grown without pigment epithelial or glial cells and in the absence of intercellular contacts, develop a complex set of photoreceptor-specific properties, including polarized structural and molecular organization and opsin immunoreactivity. We report here that these isolated embryonic photoreceptors are also capable of responding to light. Sequential photography showed that 50% of the photoreceptors grown in a light cycle elongate when exposed to light and contract in response to darkness. A smaller population (20%) showed the opposite response. Responses of individual cells could be observed during several sequential light cycles and resemble photomechanical movements in vivo [Ali, M. A. (1971) Vision Res. 11, 1225-1288]. The differentiation program expressed by isolated precursor cells, therefore, includes the capacity for highly complex functional activities that require light sensitivity. These observations raise challenging questions regarding the nature of the chromophore and pigments that mediate light-regulated behaviors of cultured photoreceptors. PMID- 8446619 TI - Gene replacement in Halobacterium halobium and expression of bacteriorhodopsin mutants. AB - A gene replacement method has been developed to express bacteriorhodopsin mutants in the archaeon Halobacterium halobium. Selectable plasmids carrying the bacterioopsin gene (bop) were integrated at the chromosomal bop locus of H. halobium. Under nonselective conditions, recombinants were isolated that had lost the integrated plasmid and retained a single chromosomal copy of the bop gene. This approach was used to construct a bop deletion strain. By using this strain, recombinants were obtained that express wild-type bacteriorhodopsin and mutants known to be defective in proton translocation. The expressed proteins were purified in a membrane fraction similar to purple membrane and were characterized in this form. UV/visible spectra of dark- and light-adapted bacteriorhodopsin from wild-type and Asp-96 mutants were identical to those of purple membrane. Arg 82, Asp-85, and Asp-212 mutants had 10- to 50-nm red shifts in their absorption maxima and showed altered light adaptation. The proton translocation activity of the wild-type samples and purple membrane was comparable, whereas the mutants had 0-60% of wild-type activity. These results support earlier studies of proton translocation mutants expressed in Escherichia coli. PMID- 8446621 TI - Evolution of maize inferred from sequence diversity of an Adh2 gene segment from archaeological specimens. AB - A segment of the nuclear gene encoding alcohol dehydrogenase 2 (Adh2) was amplified and sequenced from extracts of archaeological maize specimens up to 4700 years old and from contemporary samples. Sequence diversity in ancient maize equals that of contemporary maize. Some ancient Adh2 alleles are identical or closely related to contemporary alleles. The data suggest that the gene pool of maize is millions of years old and that domestic races of maize stem from several wild ancestral populations. PMID- 8446620 TI - Glucose-dependent insulinotropic peptide: structure of the precursor and tissue specific expression in rat. AB - Glucose-dependent insulinotropic peptide (GIP) is a 42-amino acid gastrointestinal regulatory peptide that stimulates insulin secretion from pancreatic beta cells in the presence of glucose. Approximately 7.8 x 10(5) recombinant clones of a neonatal rat intestinal cDNA library were screened by using plaque hybridization, and three clones were identified and sequenced with the dideoxynucleotide chain-termination method. The translated amino acid sequence deduced from the nucleotide sequence of the cDNA indicated that rat GIP was derived by proteolytic processing of a 144-amino acid precursor polypeptide. The mature peptide is flanked by a 43-amino acid NH2-terminal peptide that contains a 21-amino acid signal peptide and by a 59-amino acid COOH-terminal peptide. Analysis of the nucleotide and amino acid sequence of rat GIP revealed only two substitutions from the known human GIP peptide. The use of high stringency RNA blot-hybridization analysis of total RNA extracted from various organs demonstrated expression of the GIP gene in the duodenum and jejunum and, to a lesser extent, in the ileum. In addition, expression of the GIP gene was observed in the submandibular salivary gland both by RNA analysis and RIA. In response to duodenal perfusion of a 20% Lipomul meal for 60 min, duodenal mucosal GIP mRNA concentrations increased by 42.8% and 48.2% at 30 and 60 min, respectively. PMID- 8446622 TI - Linkage of Niemann-Pick disease type C to human chromosome 18. AB - We analyzed the involvement of chromosome 18 in Niemann-Pick disease type C (NPC), an autosomal recessive cholesterol-processing disorder. Within affected offspring, the chromosome 18 parental contributions were identified by using allele-specific microsatellite markers. Significant linkage of NPC to an 18p genomic marker, D18S40, was indicated by a two-point lod score of 3.84. Analysis of meiotic chromosomal breakpoint patterns among the affected individuals indicated that the NPC gene is pericentromerically localized on human chromosome 18. PMID- 8446623 TI - Purification to homogeneity and the N-terminal sequence of human leukotriene C4 synthase: a homodimeric glutathione S-transferase composed of 18-kDa subunits. AB - Human leukotriene C4 (LTC4) synthase was purified > 25,000-fold to homogeneity from the monocytic leukemia cell line THP-1. Beginning with taurocholate solubilized microsomal membranes, LTC4 synthase was chromatographically resolved by (i) anion exchange, (ii) affinity chromatography (through a resin of biotinylated LTC2 immobilized on streptavidin-agarose), and then (iii) gel filtration. The final preparation contained only an 18-kDa polypeptide. The molecular mass of the pure polypeptide was consistent with an 18-kDa polypeptide from THP-1 cell membranes that was specifically photolabeled by an LTC4 photoaffinity probe, 125I-labeled azido-LTC4. On calibrated gel-filtration columns, purified LTC4 synthase activity eluted at a volume corresponding to 39.2 +/- 3.3 kDa (n = 12). The sequence of the N-terminal 35 amino acids was determined and found to be a unique sequence composed predominantly of hydrophobic amino acids and containing a consensus sequence for protein kinase C phosphorylation. We therefore conclude that human LTC4 synthase is a glutathione S-transferase composed of an 18-kDa polypeptide that is enzymatically active as a homodimer and may be phosphoregulated in vivo. PMID- 8446624 TI - Protein dynamics in minimyoglobin: is the central core of myoglobin the conformational domain? AB - The kinetics of CO binding to the horse myoglobin fragment Mb-(32-139), the so called "mini-Mb," were investigated by laser flash photolysis in 0.1 M phosphate buffer and in buffer with 75% (vol/vol) glycerol. The reaction displays complex time courses that can be approximated satisfactorily only with a sum of five exponentials. The features of the kinetic components and a comparison of the deoxy-minus-carbonyl difference spectra of mini-Mb and horse Mb obtained under equilibrium conditions, with the kinetic difference spectra resulting from the global analysis of the traces recorded between 400 and 450 nm, show that CO binding to mini-Mb is accompanied by large structural changes. In view of the fact that mini-Mb is an approximation of the Mb-(31-105) fragment encoded by the central exon of the Mb gene, this finding is particularly relevant. On the basis of our data and previous reports [De Sanctis, G., Falcioni, G., Giardina, B., Ascoli, F. & Brunori, M. (1988) J. Mol. Biol. 200, 725-733; De Sanctis, G., Falcioni, G., Grelloni, F., Desideri, A., Polizo, F., Giardina, B., Ascoli, F. & Brunori, M. (1992) J. Mol. Biol. 222, 637-643], we propose that the protein fragment encoded by the central exon of the Mb gene is the domain responsible for ligand-linked conformational transitions, while the two terminal fragments dampen the amplitude of the structural changes that accompany ligand binding, thus rendering the protein stable and kinetically more efficient in its physiological function. PMID- 8446625 TI - Orientation of the LexA DNA-binding motif on operator DNA as inferred from cysteine-mediated phenyl azide crosslinking. AB - To address the question how the recognition helix of the LexA repressor is positioned within the major groove of operator DNA we have applied a site specific photocrosslinking approach using a LexA mutant repressor (LexA-C52) that harbors a single cysteine side chain in position 52, close to the COOH terminus of helix 3. The LexA-C52 mutant repressor has been purified and modified site specifically with the photoreactive azido compound 4-azidophenacyl bromide, giving rise to LexA-C52*. Here we show that LexA-C52* may be selectively photocrosslinked with two adjacent bases within each operator half-site. The crosslinked bases are located, respectively, 10 and 11 base pairs from the dyad axis of the operator. The crosslinking data imply that the LexA recognition helix is oriented opposite to what is generally observed for helix-turn-helix proteins and that this helix should form a steeper angle with respect to the plane of the base pairs than is observed for standard helix-turn-helix proteins. PMID- 8446626 TI - Activation of the c-Ki-ras oncogene in aflatoxin B1-induced hepatocellular carcinoma and adenoma in the rat: detection by denaturing gradient gel electrophoresis. AB - Sequence alterations in the exon 1 region of the rat c-Ki-ras gene were studied in DNA isolated from aflatoxin B1 (AFB1)-induced rat liver carcinomas and precursor lesions appearing 56 weeks after administration of the carcinogen. To detect the mutations with high sensitivity, DNA samples were analyzed by using polymerase chain reaction (PCR) amplification in conjunction with allele-specific oligonucleotide (ASO) hybridization together with a modified PCR-G+C clamp denaturing gradient gel electrophoresis (DGGE) method. Mutations in the Ki-ras gene were present in all adenomas and carcinomas examined. The predominant mutation observed was a G.C-to-A.T base transition in codon 12 (GGT to GAT). Also present, but at low frequency, was a G.C-to-T.A base transversion in the same codon (GGT to TGT). In addition, 20% of the samples contained a G.C-to-T.A transversion in the second base position of codon 12 (GGT to GTT), a mutation not previously observed in AFB1-induced rat liver tumors. These results confirm and extend our previous findings that Ki-ras mutation is a prevalent event in hepato cellular carcinogenesis induced in Fischer 344 rats by AFB1. The modified DGGE method described is applicable to the screening of multiple mutations in neoplastic lesions with high fidelity and sensitivity. PMID- 8446627 TI - Genomic position affects the expression of tobacco mosaic virus movement and coat protein genes. AB - Alterations in the genomic position of the tobacco mosaic virus (TMV) genes encoding the 30-kDa cell-to-cell movement protein or the coat protein greatly affected their expression. Higher production of 30-kDa protein was correlated with increased proximity of the gene to the viral 3' terminus. A mutant placing the 30-kDa open reading frame 207 nucleotides nearer the 3' terminus produced at least 4 times the wild-type TMV 30-kDa protein level, while a mutant placing the 30-kDa open reading frame 470 nucleotides closer to the 3' terminus produced at least 8 times the wild-type TMV 30-kDa protein level. Increases in 30-kDa protein production were not correlated with the subgenomic mRNA promoter (SGP) controlling the 30-kDa gene, since mutants with either the native 30-kDa SGP or the coat protein SGP in front of the 30-kDa gene produced similar levels of 30 kDa protein. Lack of coat protein did not affect 30-kDa protein expression, since a mutant with the coat protein start codon removed did not produce increased amounts of 30-kDa protein. Effects of gene positioning on coat protein expression were examined by using a mutant containing two different tandemly positioned tobamovirus (TMV and Odontoglossum ringspot virus) coat protein genes. Only coat protein expressed from the gene positioned nearest the 3' viral terminus was detected. Analysis of 30-kDa and coat protein subgenomic mRNAs revealed no proportional increase in the levels of mRNA relative to the observed levels of 30 kDa and coat proteins. This suggests that a translational mechanism is primarily responsible for the observed effect of genomic position on expression of 30-kDa movement and coat protein genes. PMID- 8446628 TI - In vitro culture of primary plasmacytomas requires stromal cell feeder layers. AB - Attempts to grow primary murine plasmacytomas in vitro have, to date, been largely unsuccessful. In this study, we demonstrate that long-term in vitro growth of primary plasmacytomas is accomplished by using feeder layers composed of stromal cells from the initial site of plasmacytomagenesis. The early neoplastic lines established in this manner are dependent on physical contact with the stromal layer, which is mediated in part by CD44, for growth and survival. The stromal cells provide at least two stimuli for the plasma cells, one being interleukin 6 and the second, of unknown nature, resulting from direct physical interaction that cannot be replaced by soluble factors. These plasma cell lines have been passaged for as long as 20 months yet still maintain characteristics associated with primary plasmacytomas as they will grow in vivo only in pristane-primed animals, indicating a continued dependence on the pristane-induced microenvironment characteristic of early-stage tumors. The ability to grow primary plasmacytomas in culture and maintain their "primary" properties provides a model system for detailed analysis of early events in plasma cell tumor progression involving neoplastic cells completely dependent on physical contact with a stromal feeder layer for survival and expansion. PMID- 8446629 TI - Trans-activation of glutathione transferase P gene during chemical hepatocarcinogenesis of the rat. AB - Glutathione transferase P (GST-P; glutathione transferase, EC 2.5.1.18) is known to be specifically expressed at high levels in precancerous lesions and in hepatocellular carcinomas from a very early phase of chemically induced hepatocarcinogenesis in the rat. The almost invariable occurrence of this phenotype in these lesions strongly suggests a mechanism by which GST-P gene is activated together with a crucial transforming gene of liver cells. To distinguish the two alternative possibilities--either the GST-P gene is coactivated with a closely located transforming gene by a cis mechanism or it is activated in trans by a common trans-acting factor--we carried out carcinogenesis experiments using transgenic rats harboring the bacterial chloramphenicol acetyltransferase reporter gene ligated to the upstream regulatory sequence of the GST-P gene. In each of three independent lines tested, liver foci and nodules produced by chemical carcinogens (Solt-Farber procedure) were found to express high levels of chloramphenicol acetyltransferase activity, indicating clearly that the GST-P gene is activated by a trans mechanism during hepatocarcinogenesis. PMID- 8446630 TI - Relationships between the responses of triglyceride-rich lipoproteins in blood plasma containing apolipoproteins B-48 and B-100 to a fat-containing meal in normolipidemic humans. AB - The concentration of triglyceride-rich lipoproteins containing apolipoprotein (apo) B-48 (chylomicrons) and apo B-100 (very low density lipoproteins) was measured in blood plasma of healthy young men after an ordinary meal containing one-third of daily energy and fat. Plasma obtained in the postabsorptive state and at intervals up to 12 hr after the meal was subjected to immunoaffinity chromatography against a monoclonal antibody to apo B-100 that does not bind apo B-48 and a minor fraction of apo B-100 rich in apo E. Measurements of the concentrations of components of the total and unbound triglyceride-rich lipoproteins separated from plasma by ultracentrifugation showed that about 80% of the increase in lipoprotein particle number was in very low density lipoproteins containing apo B-100 and only 20% was in chylomicrons containing apo B-48 that carry dietary fat from the intestine. The maximal increments and the average concentrations of apo B-48 and B-100 during the 12 hr were highly correlated (r2 = 0.80), suggesting that preferential clearance of chylomicron triglycerides by lipoprotein lipase leads to accumulation of hepatogenous very low density lipoproteins during the alimentary period. The composition of the bulk of very low density lipoproteins that were bound to the monoclonal antibody changed little and these particles contained about 90% of the cholesterol and most of the apo E that accumulated in triglyceride-rich lipoproteins. The predominant accumulation of very low density lipoprotein rather than chylomicron particles after ingestion of ordinary meals is relevant to the potential atherogenicity of postprandial lipoproteins. PMID- 8446631 TI - Proliferating subventricular zone cells in the adult mammalian forebrain can differentiate into neurons and glia. AB - Subventricular zone (SVZ) cells proliferate spontaneously in vivo in the telencephalon of adult mammals. Several studies suggest that SVZ cells do not differentiate after mitosis into neurons or glia but die. In the present work, we show that SVZ cells labeled in the brains of adult mice with [3H]thymidine differentiate directly into neurons and glia in explant cultures. In vitro labeling with [3H]thymidine shows that 98% of the neurons that differentiate from the SVZ explants are derived from precursor cells that underwent their last division in vivo. This report identifies the SVZ cells as neuronal precursors in an adult mammalian brain. PMID- 8446632 TI - Coherent 40-Hz oscillation characterizes dream state in humans. AB - Magnetic recording from five normal human adults demonstrates large 40-Hz coherent magnetic activity in the awake and in rapid-eye-movement (REM) sleep states that is very reduced during delta sleep (deep sleep characterized by delta waves in the electroencephalogram). This 40-Hz magnetic oscillation has been shown to be reset by sensory stimuli in the awake state. Such resetting is not observed during REM or delta sleep. The 40 Hz in REM sleep is characterized, as is that in the awake state, by a fronto-occipital phase shift over the head. This phase shift has a maximum duration of approximately 12-13 msec. Because 40-Hz oscillation is seen in wakefulness and in dreaming, we propose it to be a correlate of cognition, probably resultant from coherent 40-Hz resonance between thalamocortical-specific and nonspecific loops. Moreover, we proposed that the specific loops give the content of cognition, and a nonspecific loop gives the temporal binding required for the unity of cognitive experience. PMID- 8446633 TI - Experience-dependent plasticity in adult rat barrel cortex. AB - This study tested the hypothesis that the receptive fields (RFs) of neurons in the adult sensory cortex are shaped by the recent history of sensory experience. Sensory experience was altered by a brief period of "whisker pairing": whiskers D2 and either D1 or D3 were left intact, while all other whiskers on the right side of the face were trimmed close to the fur. The animals were anesthetized 64 66 h later and the responses of single neurons in contralateral cortical barrel D2 to stimulation of whisker D2 (the center RF) and the four neighboring whiskers (D1, D3, C2, and E2; the excitatory surround RF) were measured. Data from 79 cells in four rats with whiskers paired were compared to data from 52 cells in four rats with untrimmed whiskers (control cases). During the period of whisker pairing, the RFs of cells in barrel D2 changed in three ways: (i) the response to the center RF, whisker D2, increased by 39%, (ii) the response to the paired surround RF whisker increased by 85-100%, and (iii) the response to all clipped (unpaired) surround RF whiskers decreased by 9-42%. In the control condition, the response of barrel D2 cells to the two neighboring whiskers, D1 and D3, was equal. After whisker pairing, the response to the paired neighbor of D2 was more than twice as large as the response to the cut neighbor of D2. These findings indicate that a brief change in the pattern of sensory activity can alter the configuration of cortical RFs, even in adult animals. PMID- 8446634 TI - Amplification of nitric oxide signaling by interstitial cells isolated from canine colon. AB - The effects of nitric oxide (NO) on intracellular Ca2+ concentration ([Ca2+]i) were studied in enzymatically dispersed interstitial cells (ICs) and smooth muscle cells (SMCs) isolated from canine colon. [Ca2+]i was monitored by using fluo-3 and video fluorescence imaging techniques. Exogenous NO caused an increase in [Ca2+]i in ICs and a decrease in [Ca2+]i in SMCs. Effects of NO on ICs were not blocked by removal of extracellular Ca2+ but were blocked by ryanodine, suggesting that NO caused release of Ca2+ from intracellular stores. When [Ca2+]i was elevated in an IC by micropressure ejection of Bay K 8644, [Ca2+]i decreased in nearby SMCs, suggesting release of a diffusible substance. The diffusible substance may be NO or an NO-related substance based on blockade of transmission by NG-nitro-L-arginine methyl ester, NG-monomethyl-L-arginine, or oxyhemoglobin. The elevation of [Ca2+]i in ICs by NO, which, in turn, might cause further release of NO and elevation of [Ca2+]i, suggests a positive feedback and amplification mechanism in these cells. Elevation of [Ca2+]i in SMCs had no effect on adjacent SMCs. Our data suggest that ICs may play a central role in amplification of NO signaling and propagation of inhibitory wave fronts. PMID- 8446636 TI - A tradition we cannot afford to continue. PMID- 8446635 TI - Generation of beta-amyloid in the secretory pathway in neuronal and nonneuronal cells. AB - The cellular mechanism underlying the generation of beta-amyloid in Alzheimer disease and its relationship to the normal metabolism of the amyloid precursor protein are unknown. In this report, we show that 3- and 4-kDa peptides derived from amyloid precursor protein are normally secreted. Epitope mapping and radiolabel sequence analysis suggest that the 4-kDa peptide is closely related to full-length beta-amyloid and the 3-kDa species is a heterogeneous set of peptides truncated at the beta-amyloid N terminus. The beta-amyloid peptides are secreted in parallel with amyloid precursor protein. Inhibitors of Golgi processing inhibit secretion of beta-amyloid peptides, whereas lysosomal inhibitors have no effect. The secretion of beta-amyloid-related peptides occurs in a wide variety of cell types, but which peptides are produced and their absolute levels are dependent on cell type. Human astrocytes generated higher levels of beta-amyloid than any other cell type examined. These results suggest that beta-amyloid is generated in the secretory pathway and provide evidence that glial cells are a major source of beta-amyloid production in the brain. PMID- 8446637 TI - Is the project true to its objectives? Evaluation of the impact of Project 2000 on an acute medical ward. AB - The impact of Project 2000 has been most visible in the realms of nurse education and clinical skill mix. One of its original aims, however, was to improve the quality of patient care. This study aimed to assess whether Project 2000 has achieved its original aims in an acute medical ward. PMID- 8446638 TI - An alternative to the colostomy. Electrically stimulated neoanal sphincter for the treatment of faecal incontinence. AB - Faecal incontinence is a disabling disorder which profoundly undermines self esteem. ESNS is a new operation which may be an alternative to colostomy. Good communication, knowledge and expertise are vital in caring for patients undergoing ESNS. All treatment options should be considered for patients with faecal incontinence. PMID- 8446639 TI - Fostering a change in policy. HIV, AIDS and the neuroscience nurse. AB - As new treatments and drug therapies enable the control of opportunistic diseases associated with Aids, its neurological manifestations are becoming more prevalent. This poses new challenges to neuroscience nurses, who must reassess their attitude to and understanding of the disease. PMID- 8446640 TI - Why measure workload? AB - There have been calls for the objective measurement of nurses' workload since the 1920s. As demands on nurses' time grow, this is becoming increasingly important to ensure cost-effective care. PMID- 8446641 TI - Adopting a standardised approach. Management and assessment of infected and colonised wounds. AB - A number of clinical factors must be taken into account when diagnosing wound infection, but evidence suggests many nurses have difficulty differentiating even between pus and slough. A standardised approach is required to help nurses accurately assess colonised and infected wounds. PMID- 8446642 TI - Participation in the research process. Action research in nursing. AB - Research findings are often not applied to clinical practice because nurses do not understand them or do not know how to apply them. Action research allows nurses to undertake research in the local setting, providing ample opportunity for re-evaluation and feedback. PMID- 8446643 TI - Interpreting a moral right. Ethical dilemmas in nutritional support for terminally ill patients. AB - The decision of whether to withdraw or withhold nutritional support in terminally ill patients presents a multifaceted ethical dilemma. Any decision must, of course, be in the patient's best interests and in accordance with an interpretation of his or her wishes, but how can this be proved to be so? PMID- 8446644 TI - A bar to holistic care? Effect of patients with mental illness on nurses in paediatric settings. AB - If they are to give effective holistic care, nurses need to feel confident in caring for patients. This study reveals that lack of education and experience mean that children with mental health problems can lead to significant stress in nurses. PMID- 8446645 TI - A key to wellbeing. Oral hygiene in patients with advanced cancer. AB - Patients with advanced cancer are particularly prone to oral infections, so it is vital that a thorough mouth care routine is followed. An assessment tool was designed to help nurses evaluate their patients' oral healthcare needs, so they can be included on individual care plans. PMID- 8446646 TI - Endpiece. A chance to say goodbye. PMID- 8446647 TI - Monthly prostaglandin bibliography prepared by Sheffield University Biomedical Information Service. PMID- 8446648 TI - Do leukotrienes play a role in the regulation of proliferation of normal and leukemic hemopoietic cells? PMID- 8446649 TI - Prostaglandin F2 alpha synthesis in the hippocampal mossy fiber synaptosomal preparation: I. Dependence in arachidonic acid, phospholipase A2, calcium availability and membrane depolarization. AB - Isolated hippocampal mossy fiber synaptosomes were used to characterize control mechanisms of prostaglandin F2 alpha (PGF2 alpha) synthesis at a central mammalian synapse. Exogenous arachidonic acid stimulated the dose-dependent synthesis of PGF2 alpha, as did the addition of phospholipase A2 or the activation of endogenous phospholipase A2. Phospholipase A2 inhibitors attenuated prostaglandin synthesis, but phospholipase C inhibitors had no effect. However, a diglyceride kinase inhibitor reduced PGF2 alpha accumulation. The cyclooxygenase inhibitor ibuprofen eliminated PGF2 alpha production, while the lipoxygenase inhibitors baicalein and NDGA reduced PGF2 alpha accumulation. The CA(2+) ionophore-dependent stimulation of PGF2 alpha synthesis was abolished by Cd2+ or Ni2+. Further more, PGF2 alpha production appeared to be dependent on Ca2+ influx via L-type, but not N- or T-type, voltage-sensitive Ca2+ channels. Membrane depolarization with KC1, veratridine or 4-aminopyridine stimulated the synthesis of PGF2 alpha. This depolarization-dependent stimulation of PGF2 alpha synthesis was attenuated by L-type voltage-sensitive Ca2+ channel blockers, phospholipase A2 inhibitors, a K+ channel activator and a Na+ channel blocker. The activation of protein kinase C also led to a reduction of PGF2 alpha accumulation in depolarized nerve endings. These results may be used to suggest that PGF2 alpha production by hippocampal mossy fiber synaptosomes was controlled by the Ca(2+)- and phospholipase A2-dependent accumulation of unesterified arachidonic acid and was modulated by membrane depolarization and the activity of protein kinase C. PMID- 8446650 TI - Lipid intake during pregnancy in developing countries: possible effect of essential fatty acid deficiency on fetal growth. AB - There is a strong epidemiological association between poor nutritional status and low-birthweight (LBW) newborns. According to the World Health Organization (WHO), 95% of total LBW in the world are born in developing countries. Nevertheless, the nutritional etiology of intra uterine growth retardation (IUGR) is still controversial and not yet established largely because of contradictory nutritional studies in pregnancy. In 1981 Menon et al described an animal model of IUGR due to mild deficiency in essential fatty acids (EFA, linoleic and alpha linolenic acids), with a strong correlation between EFA intake during pregnancy and fetal growth. According to the WHO reports in the last decade, there was a dramatic deficiency of lipid intakes (less than 10% of total caloric amounts) in the majority of developing countries while the EFA requirements alone of normal nourished women are evaluated at 6% of total caloric amounts during pregnancy. A mild deficiency in dietary EFA may be a limiting factor in fetal growth processes in humans as it has been shown in animals. Such a mechanism could be easily verified. Research proposals are made in an attempt to test this hypothesis in developing countries with possible applications in further nutritional interventions in pregnancy. PMID- 8446651 TI - Type A behavior and alcohol consumption: effects on resting and post-exercise bleeding time thromboxane and prostacyclin metabolites. AB - The vasoactive eicosanoids, prostacyclin and thromboxane, are thought to play an important role in the genesis of cardiovascular disease. Since an altered basal production of these eicosanoids among individuals exhibiting the Type A behavior pattern had previously been observed by the authors, the present study evaluated the extent to which the TABP-eicosanoid relationship would be altered by two lifestyle variables known to affect platelet activity: alcohol consumption and stressful physical activity. 55 male participants aged 18-25 years, participated in the study. They were classified as either Type A or Type B on the basis of the Structured Interview and as either moderate, heavy, or abstinent alcohol drinkers. Bleeding times were performed and bleeding time thromboxane and prostacyclin metabolites were measured in all subjects both before and following treadmill exercise. The results indicated that following exercise, Type A participants, who reported moderate alcohol intake, had decreased levels of thromboxane B2 formation relative to Type As reporting heavy consumption. Further, prostacyclin production, measured as the primary metabolite, 6-keto prostaglandin F1 alpha, was significantly suppressed following exercise among drinkers as compared with participants reporting abstinence. These results were discussed in relation to the proposition that moderate alcohol consumption reduces coronary heart disease risk. PMID- 8446652 TI - A comparison of hepatic, splenic, peritoneal and alveolar macrophages with respect to PGE2, TXB2, production and ADCC function. AB - The in vitro production of PGE2 and TxA2, measured as TxB2, and the antibody dependent cellular cytotoxicity (ADCC) as well as spontaneous cellular cytotoxicity (SCC) displayed by hepatic, peritoneal, splenic, and alveolar macrophages from 12 rats was determined and compared. Kupffer cells, the fixed macrophages of the liver, were the most active cells in the production of PGE2. Kupffer cells and peritoneal macrophages released about equal amounts of TxB2 which was much higher than that released by splenic macrophages. Kupffer cells displayed the strongest ADCC activity, and alveolar macrophages had the lowest value. These results confirm the previously reported heterogeneity among different sources of macrophages and emphasize the enhanced activity of Kupffer cells with respect to eicosanoid production and ADCC function. PMID- 8446653 TI - Effect of pravastatin on fatty acid profile of low density lipoprotein in patients with hypercholesterolemia. AB - We gave pravastatin, an HMG-CoA reductase inhibitor, to 21 hypercholesterolemic patients for 12 weeks after they had been on dietary therapy for 12 weeks. In addition to inducing a significant reduction of total cholesterol and LDL cholesterol, pravastatin significantly decreased the proportion of linoleic acid (18:2) and increased that of saturated (FA) (16:0 and 18:0) in the cholesterol ester of LDL. Linoleic acid was also reduced in the triglyceride of LDL. Besides, monounsaturated FA (16:1 and 18:1) were increased in the cholesterol ester, triglyceride and phospholipid of LDL, but the changes in monounsaturated FA were not statistically significant. The effect of pravastatin on the FA profile of LDL was similar to that of fibric acid derivatives. The mechanism as well as the clinical implication of these changes await further investigation. PMID- 8446654 TI - The pharmacokinetics and pharmacodynamics of the prostacyclin analog 15AU81 in the anesthetized beagle dog. AB - 15AU81, a tricyclic benzindene analog of prostacyclin, is currently under preclinical evaluation as a potential treatment for congestive heart failure. The cardiovascular effects of 15AU81 were evaluated in anesthetized beagle dogs given 4-h infusions at rates of either 0.1, 0.3, 1.0, or 3.0 micrograms/kg/min. Plasma samples taken from these dogs prior to, during, and after the infusion, were analyzed for 15AU81 by a radioimmunoassay (RIA). This report integrates the vasodilatory effects and plasma concentration data from the 15AU81 infusion study. Pharmacokinetic analysis of mean data indicated a biphasic decay of 15AU81 in plasma, with an initial half-life of approximately 2 min, and a terminal half life of approximately 20 min. Visual inspection of plots of drug effect and drug concentration against time indicated a close relationship between plasma concentration of 15AU81 and the onset of decreases in total peripheral resistance (TPR) and pulmonary vascular resistance (PVR). In general, the decreases in TPR and PVR induced by 15AU81 were maintained during infusion. Concentration-effect plots indicated some hysteresis in TPR vs plasma concentrations of 15AU81 after termination of the infusion; possible explanations for this hysteresis include the presence of saturating concentrations of 15AU81 at the effect site, with a delay in the clearance of 15AU81 from the effect site compared to its clearance from plasma, and/or the presence of active metabolites at the effect site. A fit of the TPR and PVR data to the Emax pharmacodynamic model predicted that the maximum decrease in TPR achievable with 15AU81 in anesthetized dogs was 66%, and that the concentration of 15AU81 producing 50% of the maximum effect (EC50) was 8.6 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446655 TI - Radioimmunoassay for the chemical stable prostacyclin analog, 15AU81: a preliminary pharmacokinetics study in the dog. AB - 15AU81 is a chemically stable tricyclic benzindene analog of prostacyclin, with possible application to the treatment of congestive heart failure. Effective pharmacological doses in a dog model are in the microgram to sub-microgram/kg range, necessitating an analytical method of high sensitivity for determination of the drug in plasma. This report describes the development and validation of a radioimmunoassay for 15AU81, and its application to a pharmacokinetic study in the beagle dog. An antiserum elicited by immunization with a 15AU81-bovine thyroglobulin conjugate was employed, along with 3H-15AU81, in the radioimmunoassay. Analogs of 15AU81, as well as a glucuronide metabolite produced by a dog liver subcellular fraction in vitro, were used to demonstrate the specificity of the radioimmunoassay. Specificity was confirmed by comparative analysis by radioimmunoassay and by a quantitative GC/MS procedure of plasma samples from dogs dosed with 15AU81. The limit of quantitation in dog plasma was 1.6 ng/ml; accuracy and precision were both acceptable. The assay was applied to a study of the pharmacokinetics of 15AU81 in the beagle dog after intravenous or intratracheal administration of a single 20-micrograms/kg dose. Following intravenous dosing, 15AU81 was eliminated rapidly from plasma (t1/2, 2.8 min), while after intratracheal administration, clearance appeared to be somewhat slower and bioavailability was appreciable (mean, 46%), suggesting that this route of administration may be worthy of further evaluation. PMID- 8446656 TI - Immunohistochemical localization of PGF2 alpha receptor in the rat oviduct. AB - As a step towards understanding the role of prostaglandin F2 alpha (PGF2 alpha) in female reproductive tract physiology, a rabbit polyclonal antiserum reactive with purified PGF2 alpha receptor (PGF2 alpha-R) was produced. Here we describe use of this anti-PGF2 alpha-R antiserum in immunohistochemical staining of rat oviduct to ascertain which cell types, in vivo, possess immunoreactive PGF2 alpha R. Western blot analysis was initially performed and confirmed that the anti-PGF2 alpha-R antiserum recognizes only one oviductal antigen. The immunopositive antigen is similar in molecular mass (by PAGE) to the previously described, purified PGF2 alpha-R molecule. Immunohistochemical staining demonstrates that adult rat oviduct contains a single subpopulation of cells with PGF2 alpha-R, and that subpopulation is a ciliated epithelial cell type found predominantly in the isthmus and distal ampullae near the isthmus-ampullae junction (I-AJ). None of these PGF2 alpha-R immunopositive cells are found in the epithelium of infundibulum oviduct. PGF2 alpha-R containing cells are not randomly distributed in the epithelium on cross-section of the isthmus and ampullae oviduct, rather, they are almost always in the crypts between infoldings of the mucosa. The relative number of this I-AJ PGF2 alpha-R containing epithelial cell subpopulation appears to vary with the phase of the rat's estrus cycle. Diestrus I-AJ epithelium contains one-half to one-third as many PGF2 alpha-R containing cells as it does in proestrus, estrus or metestrus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446657 TI - Protective effect of diclofenac sodium against endotoxic shock in anaesthetized pigs. AB - The effect of diclofenac sodium was investigated on haemodynamics, haematologic and blood glucose values as well as the release of eicosanoids, tumor necrosis factor (TNF) and platelet activating factor (PAF) in anaesthetized pigs receiving 5 micrograms.kg-1 Escherichia coli lipopolysaccharide (LPS) over 60 min into the superior mesenteric artery. The animals were observed for an additional period of 2 h after the termination of LPS infusion. 15 of the 31 animals infused with LPS and not treated with diclofenac sodium died within 30 min after the commencement of LPS infusion (non-survivors), while the other 16 survived the experimental period of 3-h, though in a shock state (survivors). No alterations were observed in plasma concentrations of PAF or eicosanoids (TXB2, 6-keto PGF1 alpha and LTB4), but a marked increase was detected in TNF release in the non-survivors. A significant, though transient, increase in concentrations of PAF, TNF and eicosanoids studied characterized the survivors. Another group of 7 LPS-infused pigs was treated with diclofenac sodium (2 mg, kg-1, i.v. bolus 60 min before the start of LPS infusion, followed by a continuous infusion of 1 mg kg-1 h-1) 1 mg/kg-1/h-1. This treatment prevented death and shock despite the high concentrations of TNF and PAF. Concentrations of both cyclooxygenase and 5 lipoxygenase enzymes products were reduced. These data indicated that the beneficial effect of diclofenac sodium in LPS induced shock may be related to the reduced production of eicosanoids. PMID- 8446658 TI - Withdrawal from continuous or intermittent cocaine: effects of NAN-190 on cocaine induced locomotion. AB - Rats were pretreated with 40 mg/kg/day cocaine for 14 days by either SC injections or osmotic minipumps. Rats were then withdrawn from the pretreatment regimen for 7 days. In Experiment 1, rats received 0- to 2.0-mg/kg IP injections of 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine (NAN-190), a putative 5-hydroxytryptamine1A (5-HT1A) receptor antagonist. In Experiment 2, rats received the same doses of NAN-190 in combination with a 15-mg/kg IP injection of cocaine. The results of Experiment 1 indicate that the continuous-infusion group demonstrated a dose-dependent suppression of locomotor behavior by single doses of NAN-190. NAN-190 had no consistent dose-dependent effect on the locomotor behavior of subjects in the other pretreatment groups. The results of Experiment 2 indicate that rats receiving intermittent, daily injections tended to exhibit behavior consistent with 5-HT1A receptor supersensitivity. In contrast, rats receiving continuous cocaine tended to exhibit behavior consistent with 5-HT1A receptor subsensitivity. Changes in 5-HT1A receptor sensitivity may contribute to some of the anxiety and depressive symptoms exhibited by human cocaine abusers. PMID- 8446659 TI - Taurine and ethanol-induced conditioned taste aversion. AB - It has been reported that acute, simultaneous injections of taurine and ethanol were effective in reducing ethanol-induced locomotor activity and sleep time. The possible involvement of taurine administration in ethanol-induced conditioned taste aversion (CTA) was investigated. The results obtained in the present study following simultaneous administration of taurine (45 mg/kg) and ethanol (0.8, 1.2, and 1.6 g/kg) demonstrate a significant interaction between taurine and ethanol in their effect on ethanol-induced CTA in rats. This interaction was biphasic in nature and dependent upon the specific dose of ethanol. At the lowest ethanol dose (0.8 g/kg), which in itself resulted in a marginal CTA, taurine significantly enhanced the CTA induced by this dose. The intermediate ethanol dose of 1.2 g/kg produced a significant CTA. This CTA was blocked by administration of taurine. Finally, the CTA produced by the high dose of ethanol (1.6 g/kg) was not affected by administration of taurine. Taurine by itself does not produce a CTA. Peripheral levels of ethanol were ethanol dose dependent and the same in all animals regardless of treatment, indicating taurine had no effects on plasma ethanol levels. These data are similar to those obtained by earlier studies on the effects of taurine on ethanol-induced motor activity in mice. The present results support the findings reported by other investigators that taurine administration exerts a significant effect on ethanol-induced behaviors. PMID- 8446660 TI - Conditioning of the allogeneic cytotoxic lymphocyte response. AB - Allogeneic cytotoxic T-lymphocyte (CTL) response can be obtained following immunization of BALB/c mice with C57BL/6 spleen cells. We investigated the possibility of behaviorally conditioning this response by associating the C57BL/6 spleen cell immunization [unconditioned stimulus (US)] with camphor odor [conditioned stimulus (CS)]. We reported the possible mechanisms involved in the conditioning of natural killer cell activity. Similar approaches were used to investigate the mechanisms that participate in the conditioned CTL activity. The first mechanism of investigation utilized opioid receptor blockers naltrexone and quaternary naltrexone. Naltrexone, which blocks both the central and peripheral opioid receptors, blocked the recall of the conditioned response, whereas quaternary naltrexone, which does not penetrate the blood-brain barrier, was unable to block the conditioned response, demonstrating that centrally located opioid receptors play a role in the recall of the conditioned response. The studies are of interest because they indicate that resistance or susceptibility to various diseases such as cancer, autoimmunity, and infectious diseases might be influenced by the regulatory network of the CNS. PMID- 8446661 TI - Cocaine attenuates puberty acceleration in female house mice. AB - The onset of puberty in female house mice is advanced by exposure to a male urinary pheromone. This study tested whether cocaine could modify the juvenile female mouse's response to this pheromone. Puberty acceleration, as measured by uterine weight change, is inhibited by daily SC administration of 30 or 40 mg/kg body weight cocaine HCl between 20 and 26 days of age. Two daily injections of 20 mg/kg cocaine reduced both uterine development and body weight gain. Thus, cocaine may reduce an animals' reproductive fitness by isolating it from its social environment. At higher doses, cocaine can delay body growth, as well as the onset of puberty. PMID- 8446662 TI - Effects of psychoactive drugs or stress on learning, memory, and performance as assessed using a novel water maze task. AB - A novel water maze was used to assess the potential performance-disrupting effects of psychoactive drugs and stressors (4 mg/kg amphetamine sulfate; 1, 2, or 4 mg/kg diazepam; 30 mg/kg caffeine; 5 or 30 mg/kg atropine sulfate; 15 min of either intermittent foot-shock, forced running, or immobilization). The task utilized a traditional type of maze with walls and doorways set inside a pool. The apparatus could easily be reconfigured to present different mazes of approximately equal difficulty by opening or closing multiple doorways. Performance was measured by number of errors and time required to swim from the "start" to "finish" (a raised platform not in the rat's line of sight). After initial maze training, rats were divided into two groups. One group ran three daily trails through the same maze each day; this group was used to assess memory. The second group was challenged to swim three consecutive trials in a new maze configuration each day as a measure of learning. On any given day, rats from both groups received the same treatment. Drug or stress treatments were interspersed with vehicle or no-treatment trials days. The new maze task was more sensitive than the well-learned maze to the performance disrupting effects of amphetamine, caffeine, and diazepam, while atropine had no significant effect on performance on either maze. Foot-shock stress impaired performance on both mazes, while the other stressors had no significant effect. PMID- 8446663 TI - Unilateral locus coeruleus lesions facilitate motor recovery from cortical injury through supersensitivity mechanisms. AB - Previous research has indicated that noradrenergic infusions into the cerebellum contralateral to a sensorimotor cortex injury facilitate recovery of motor function. In the present study, the locus coeruleus was lesioned at 2 weeks prior to, 1 week prior to, or simultaneous with a right sensorimotor cortex injury, and functional recovery in response to noradrenergic cerebellar infusions was measured using the beam-walk task. When the locus coeruleus lesion was separated from the sensorimotor cortex lesion by 1 week or more, noradrenergic-induced facilitation of functional recovery occurred with the greater effects observed at the 2-week interval. Simultaneous locus coeruleus and sensorimotor cortex injury with cerebellar noradrenergic infusions revealed no difference in functional recovery. The results suggest that denervation supersensitivity and/or sprouting developed in the cerebellum following the locus coeruleus lesions if a sufficient amount of time elapsed before the sensorimotor cortex injury. The heightened sensitivity to noradrenergic infusions in the contralateral cerebellum suggests that noradrenergic changes in this structure underlie the acceleration of functional recovery from the cortical injury. PMID- 8446664 TI - Effects of in utero administration of alcohol on alcohol sensitivity in adult rats. AB - In utero exposure to alcohol has been associated with many physical deficits and behavioral abnormalities. The purpose of these studies was to determine the effects of in utero administration of alcohol on behaviors related to tolerance and sensitivity to alcohol in adult rats. Pregnant rats were maintained on a liquid diet containing alcohol [35% ethanol-derived calories (EDC)] throughout pregnancy. Offspring manifested physical characteristics of Fetal Alcohol Syndrome. The 35% EDC group was able to stay on a wooden dowel longer and at higher blood alcohol concentrations than were pair-fed controls. Following a hypnotic dose of alcohol, rats in the 35% EDC group slept longer than pair-fed controls. A greater alcohol-induced hypothermic effect was seen in females in the 35% EDC group than in controls. Treatment did not affect rate of metabolism of alcohol. These studies suggest that in utero administration of alcohol may be a factor in determining an individual's sensitivity and tolerance to alcohol and possibly their preference for alcohol. PMID- 8446665 TI - MAO-A and -B inhibitors selectively alter Xenopus mucus-induced behaviors of snakes. AB - Skin mucus of the frog Xenopus laevis, contacted orally by snakes, induces dyskinetic oral movements and climbing behavior that promote escape. The mucus contains peptides and indoleamines known to produce drug-induced movement disorders in other species. We hypothesized that inhibition of monoamine oxidase A (MAO-A) by N-methyl-N-propargyl-3-(2,4-dichlorophenoxy)-propylamine [clorgyline (CLG)] and MAO-B by R(-)-N, alpha-Dimethyl-N-2-propynyl-benzene-ethanamine [L deprenyl (LDL)] would selectively modify mucus-induced behaviors by elevating norepinephrine and serotonin (with CLG), phenylethylamine (with LDL), or dopamine (with both drugs). In Experiment 1 (EXP1), adult snakes received mucus and/or 20 micrograms/g (IP) of both drugs. In EXP2, juveniles received mucus and/or 5, 10, and 20 micrograms CLG or LDL. CLG given alone had no effect on tongue flicking, activity, and climbing (EXP1,2). LDL alone decreased tongue flicking in EXP2 and increased climbing (EXP1,2). Given with mucus, both drugs further lowered the tongue flicking rates attenuated by mucus (EXP1,2); only LDL potentiated mucus induced climbing. Yawning was the only mucus-induced dyskinesia attenuated (20 micrograms CLG, adults; 20 micrograms LDL, juveniles). We suggest that dopamine and/or phenylethylamine, the substrates for MAO-B, may promote mucus-induced climbing and tongue flicking but may have some protective role against mucus induced yawning in water snakes. PMID- 8446666 TI - Efficacy of physostigmine as a pretreatment for organophosphate poisoning. AB - Continuous administration of the carbamate physostigmine, producing approximately 40% serum cholinesterase (ChE) inhibition, provides significant protection against the lethal effects of the organophosphorous nerve agent pinacolyl methylphosphonofluoridate (soman). Rats pretreated with physostigmine were also protected against the development of cholinergic symptoms and loss of body weight. Soman and physostigmine both inhibit ChE, yet animals pretreated with physostigmine exhibited less ChE inhibition in serum and brain than did animals exposed to soman alone. In addition, there did not appear to be any additive effect of presenting both anticholinesterases simultaneously. To further examine the effectiveness of physostigmine, we compared the results of this study with previously collected pyridostigmine data from our laboratory. This comparison indicates that physostigmine is more effective than pyridostigmine in protecting against the detrimental effects of soman. PMID- 8446667 TI - Discriminative stimulus effects of the PCP/sigma-ligand (+)-N-allylnormetazocine in monkeys. AB - (+)-N-Allylnormetazocine [(+)-NANM] binds to both the phencyclidine (PCP) receptor and the sigma-site in brain, with some selectivity for the latter. In rats, the discriminative stimulus effects of (+)-NANM are primarily PCP like. The present study was performed to determine if the discriminative effects of (+) NANM in a primate species might reflect the actions of this drug at the sigma site. Six squirrel monkeys were trained to discriminate between IM injections of saline and 1.0 mg/kg (+)-NANM in a two-choice discrete-trial avoidance procedure. In tests of stimulus generalization, dose-dependent increases in trials completed on the (+)-NANM choice lever were produced by (+)- and (-)-NANM, by PCP and the PCP-like drugs MK-801 and thienylcyclohexyl-piperidine, and by the opioids (+)- and (-)-cyclazocine and dextrorphan; order of potency correlated with reported affinities for the PCP receptor. High-affinity sigma-ligands, (+)-pentazocine, 1,3-di-ortho-tolylguanidine (DTG), haloperidol, and BMY 14802, as well as agonists at mu- and kappa-opioid receptors, occasioned selection of the saline appropriate choice lever. Selection of the (+)-NANM choice lever was reduced by up to 35-50% when 1.0 mg/kg (+)-NANM was given concurrently with haloperidol or BMY 14802, but was not affected substantially by (-)-butaclamol, another sigma ligand, or by naltrexone, an opioid antagonist. The discriminative effects of (+) NANM in squirrel monkeys appear to be mediated largely by the PCP receptor and not by the sigma-site or opioid receptors. PMID- 8446668 TI - Hypothermia induced by hyperbaric oxygen is not blocked by serotonin antagonists. AB - Exposure to HBO causes hypothermia, bradycardia, head weaving, resting tremor, piloerection, and straub tail in rats. These physiological and behavioral responses can also be evoked by selective activation of serotonin1A (5-HT1A) receptors. The purpose of the current study was to determine if hypothermia caused by HBO is due to increased activation of 5-HT1A receptors. The levels of brain biogenic amines were measured in brain regions of Sprague-Dawley (SD) rats exposed to HBO. Exposure to HBO caused an increase in the levels of 5 hydroxyindoleacetic acid (5-HIAA) in the striatum (92%, p < 0.05) and occipital temporal cortex (116%, p < 0.05), but not in other brain regions. Exposure to HBO did not change the levels of tryptophan, serotonin (5-HT), other biogenic amines, or their metabolites. It is hypothesized that the Fawn Hood (FH) rat, which is reported to be resistant to hypothermia induced by 8-hydroxy-2-(di-n propylamino)tetralin (8-OH-DPAT), has an abnormality of 5-HT1A receptor activity. Although the FH rat was more resistant to hypothermia induced by HBO than the SD rat, we were not able to confirm that this rat was resistant to hypothermia induced by 8-OH-DPAT. The 5-HT receptor antagonists, 1-(1H-Indol-4-yloxy)-3-[(1 methylethyl)amino]-2-propanol (Pindolol), 1-(2-methoxyphenyl)-4-[4-(2 phthalimido)butyl] piperazine hydrobromide (NAN-190), and methysergide, did not block hypothermia induced by HBO in SD rats. A series of control experiments were used to confirm that the antagonists blocked hypothermia induced by serotonin agonists.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446669 TI - Effects of repeated administration of corticotropin-releasing factor on schedule controlled behavior in rats. AB - To examine the effects of repeated administration of corticotropin-releasing factor (CRF) on behavior, rats were administered ICV injections of either CRF or saline on alternate days for 10 days prior to performing on a multiple fixed interval (FI) 60 s/fixed-ratio (FR) 20 schedule for food reinforcement. A daily session consisted of 10 components of each schedule that alternated, starting with the FI component. CRF doses were individually determined for each rat and were either 1.0, 3.0, or 10 micrograms CRF based upon the dose that occasioned more than a 50% reduction in the rate of responding. Acute administration of CRF decreased the rate of responding in both components well below control rates; this decrease in responding was associated with a 20 or 50% decrease in the number of earned reinforcements in the FI and FR components, respectively. With repeated administration, CRF-induced suppression of responding was attenuated, although CRF continued to decrease response rate. Despite the continued reduction in response rate, subsequent CRF injections did not result in a loss of reinforcements in the FI component, whereas rats continued to lose 20% of the reinforcers in the FR component. After an 18-day hiatus in which no CRF was administered, the baseline rate of responding on the multiple schedule increased, in particular in the FI component. When CRF was readministered, response rates were slightly suppressed relative to a reestablished saline control but significantly higher than CRF-induced suppression on the last day of the chronic regimen. These data demonstrate that with repeated administration tolerance develops to CRF-induced suppression of responding in rats. PMID- 8446670 TI - Effects of 5-hydroxytryptamine3 antagonist, ondansetron, on cigarette smoking, smoke exposure, and mood in humans. AB - Recent studies in the animal laboratory indicate that 5-hydroxytryptamine3 (5 HT3) antagonists reduce the reinforcing effects of several psychoactive drugs, including nicotine. The purpose of our study was to determine if ondansetron, a selective 5-HT3 antagonist, affected tobacco cigarette consumption in smokers. In the first experiment, a prospective, crossover, placebo-controlled trial was used in which subjects (N = 7) were exposed in an inpatient research unit to 0, 0.15, 0.3, or 0.45 mg/kg ondansetron in three equally divided doses given 4 h apart. In the second experiment, seven different subjects were exposed to the same trial except the dose range was reduced to about 10%: 0, 0.01, 0.02, or 0.04 mg/kg. In each experiment, order of dosing conditions was determined by a Latin square design. Dependent measures included number of cigarettes smoked during the 24-h session, biologic exposure levels (carbon monoxide and plasma nicotine levels), and mood. Number of cigarettes smoked and biologic exposure levels did not differ across drug conditions in either experiment. There were also no effects of ondansetron on mood. From our study results, we conclude that acute administration of ondansetron, at doses appropriate for antiemesis or at markedly lower doses, does not alter tobacco consumption or smoke exposure in humans. PMID- 8446671 TI - Effects of caffeine on recognition. AB - The present study examined the effects of caffeine on recognition performance after acquisition of conceptual and acoustic tasks. Following a between-subject design, 300 male postgraduate students classified as high or low impulsives received either placebo or one of four doses of caffeine citrate (1, 2, 3, and 4 mg/kg body weight). A double-blind procedure was adopted for drug administration. Caffeine facilitated recognition performance after acoustic acquisition but impaired it after conceptual acquisition in high impulsives. The drug had no influence on recognition performance of low impulsives. PMID- 8446672 TI - Operant responding controlled by milk or milk contaminated with alcohol as positive reinforcers in infant rats. AB - Infant rats during the first, second, or third week of life were tested in operant conditioning with uncontaminated milk or milk supplemented with 6.0% v/v absolute ethanol (EtOH) as the reinforcer. Relative to yoked controls, pups of each age group reinforced on a response-contingent basis exhibited a significantly higher rate of responding with either reinforcer. In terms of amount of reinforcement, milk induced a higher rate of lever pressing than did the EtOH-contaminated compound. Age-related differences in the onset of differential responding for plain milk and EtOH-contaminated milk suggested developmental changes in the effects of alcohol. In a second experiment, forced drinking of milk and EtOH-contaminated milk was compared in similar age groups. Patterns of intake resembled the patterns of operant responding controlled by the same substance in the first experiment. These experiments indicate that the presence of alcohol in milk partially inhibits the reinforcing capacity of uncontaminated milk. Nevertheless, the former compound is still effective as a positive reinforcer during the first weeks of life. PMID- 8446673 TI - Effects of p-chlorophenylalanine and methysergide on the performance of a working memory task. AB - The present study investigated the effects of serotonergic dysfunction on working memory. Therefore, the effects of inhibition of serotonin [5-hydroxytryptamine (5 HT)] synthesis induced by p-chlorophenylalanine (p-CPA) and pharmacological blockade of 5-HT receptors by methysergide on the performance of rats in a delayed nonmatching to position task assessing spatial working memory were studied. Methysergide (1.0, 5.0, or 15.0 mg/kg) significantly disrupted behavioral activity of rats and decreased the percent correct total responses. However, the impairment in the percent correct responses was delay independent, indicating a nonmnemonic disruption of the performance. p-CPA (500 mg/kg/day x 3) induced an almost total depletion (> 97%) of frontal cortical and hippocampal serotonin and its major metabolite 5-hydroxyindoleacetic acid and slightly affected noradrenergic and dopaminergic systems. p-CPA treatment did not affect the percent correct responses. However, the behavioral activity of rats was slightly decreased by p-CPA. The disruptions in behavioral activity and the percent correct responses induced by methysergide (2.0 mg/kg) were not abolished by p-CPA. The present results do not support any important role for the serotonergic system in spatial working memory as assessed using the delayed nonmatching to position task. PMID- 8446674 TI - Phencyclidine disrupts acquisition and retention performance within a spatial continuous recognition memory task. AB - Rats with 1 or 2 mg/kg phencyclidine (PCP), 4 mg/kg PCP, or saline injections were tested for acquisition or retention performance of a spatial continuous recognition memory task. Results indicate that relative to controls and rats with injections of 1 and 2 mg/kg PCP rats with 4-mg/kg PCP injections were profoundly impaired in acquisition and somewhat impaired in retention of the task across all lags as measured by increases in latency for repeated items. Phencyclidine, through it presumed blocking action of the NMDA receptor, alters the consolidation of new spatial location information but does not have a major affect on short-term maintenance of previously learned information. PMID- 8446675 TI - Effects of scopolamine on the rewarding and seizure-inducing properties of amygdaloid stimulation. AB - The relationship between amygdaloid brain-stimulation reward and the evolution of seizure activity was evaluated in this study. Current levels that maintained optimal intracranial self-stimulation (ICSS) rates were found to be lower than the minimal current intensity required to elicit an afterdischarge (AD) from the central nucleus of the amygdala. After the ICSS session, AD thresholds (ADTs) were reduced to the same levels of current used to support ICSS. Assessment of seizure stage development during ICSS testing revealed that the emergence of early-stage epileptiform events following repeated amygdaloid stimulation suppressed ICSS performance. While administration of the antimuscarinic scopolamine did not prevent the stimulation-elicited reduction in AD thresholds, it was observed to inhibit seizure progression and increase ICSS rates. These results are consistent with the excitatory function of acetylcholine in epileptogenesis and were related to the possibility that different mechanisms underlie the rewarding and seizure-inducing properties of amygdaloid stimulation. PMID- 8446676 TI - Effects of dopamine D1 antagonists SCH23390 and SK&F83566 on locomotor activities in rats. AB - The effects of the dopamine D1 antagonists R-(+)-7-chloro-8-hydroxy-3-methyl 1phenyl-2,3,4,5-tetrahydro-1-H-3 -benzazapine (SCH23390) and (+-)-7-bromo-8 hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1- H-3-benzazapine (SK&F83566) were tested for 2 h on linear locomotor, rearing, stereotypy, and margin times in an open field. Each of the antagonists attenuated the duration of linear locomotion, rearing, and stereotypy times in a dose- and time-dependent manner. The effectiveness of the antagonists was relatively brief and SCH23390 was more effective than SK&F83566 on each behavior. The two antagonists had differential effects on margin time. PMID- 8446677 TI - Stress-induced hypoalgesia and defensive freezing are attenuated by application of diazepam to the amygdala. AB - Recent studies have shown that lesions of the amygdala, as well as systemic administration of benzodiazepine receptor agonists, block the hypoalgesia and defensive behavior normally observed when rats are exposed to stimuli associated with shock. The present study was conducted to determine if the direct application of a small quantity of the benzodiazepine diazepam (DZP) to the amygdala would affect defensive freezing and hypoalgesia as measured by the formalin test. Independent groups of rats were prepared with chronic cannulae aimed at the basolateral or central regions of the amygdala. Bilateral injection of DZP (30 micrograms) into the basolateral amygdala attenuated both the defensive freezing behavior and the hypoalgesia seen during an 8-min period following a series of three brief foot-shocks. The same dose of DZP applied to the central amygdala attenuated the freezing response, although this effect may have been due to limited diffusion of the drug into the basolateral region. Baseline levels of formalin-induced behavior were not affected by DZP in either group. These results support the idea that hypoalgesia is one component of an integrated defensive response shown by rats in anxiety- or fear-related situations and that the amygdala represents an important forebrain component of a neural circuit that subserves the expression of this response. PMID- 8446678 TI - Effects of oxiracetam, physostigmine, and their combination on active and passive avoidance learning in mice. AB - The nootropic drug oxiracetam (50 and 100 mg/kg) had no effect on one-trial passive avoidance acquisition in CD-1 mice, while the acetylcholinesterase inhibitor physostigmine improved passive avoidance performance at doses of 0.025 and 0.05 mg/kg given either pre- or posttraining. In a multitrial avoidance task (shuttle-box), a consistent tendency to better performance was displayed by mice receiving oxiracetam (50 and 100 mg/kg) or physostigmine (0.01 and 0.025 mg/kg, but not 0.05 mg/kg). Combinations of the two drugs never improved active or passive avoidance performance more than drugs given separately. This indicates no advantage in combining nootropics and anticholinesterase inhibitors to improve learning and memory. PMID- 8446679 TI - Different effects of methylxanthines on central serotonergic postsynaptic neurons in a mouse behavioral model. AB - Effects of the four methylxanthines (100 mg/kg, IP)--caffeine, theophylline, theobromine, and pentoxifylline--on the central serotonergic neuron were studied in mice using a behavioral model, the head-twitch response. The four methylxanthines potentiated the head twitches induced by 5-hydroxytryptophan (5 HTP) in pargyline-pretreated mice; pentoxifylline was the most potent. The potentiating effect of pentoxifylline was increased by paroxetine, the selective inhibitor of uptake of 5-hydroxytryptamine (5-HT), but those of the other drugs were not. In nontreated animals, caffeine directly induced head-twitch responses, which were not affected by pargyline pretreatment but were increased by prior treatment with 5,7-dihydroxytryptamine (5,7-DHT). The number of head twitches produced by caffeine in 5,7-DHT-treated mice was increased twofold by p chlorophenylalanine (p-CPA), the tryptophan hydroxylase inhibitor. In mice treated with both 5,7-DHT and p-CPA, theophylline induced the responses, although much less potently than caffeine. Theobromine and pentoxifylline produced even fewer responses. From the results of the present study, it may be concluded that the methylxanthines possess qualitatively different actions on the central serotonergic neuron; caffeine and theophylline appear to have direct effects on the postsynaptic neuron, but theobromine and pentoxifylline do not. PMID- 8446680 TI - Anxiogenic stimuli in the elevated plus-maze. AB - Untreated rats normally avoid the open arms of the "elevated plus-maze," preferring instead the closed arms, whereas rats treated with antianxiety drugs (e.g., diazepam) show far less open-arm avoidance. Although it has often been assumed that rats avoid the open arms because of novelty, height, or open space, the anxiogenic role of these stimuli in the plus-maze has not been systematically examined. In Experiment 1, rats were repeatedly exposed to the elevated plus-maze with the expectation that their "fear" of the open arms would habituate over trials. Instead, open-arm avoidance actually increased on the second trial and showed no evidence of habituating after 18 trials. In Experiment 2, three 30-min sessions of confinement to the open arms ("flooding") failed to decrease rats' open-arm avoidance. Instead, rats that had received flooding avoided the open arms significantly more than control rats during the first test. Experiment 3 showed that although diazepam-treated rats avoided the open arms less than vehicle-controls on the first test this difference dissipated across test trials. Further, diazepam had no carryover effect on rats' subsequent avoidance of the open arms in a nondrugged state. In Experiment 4, plus-maze height was varied from 50 to 6 cm, but rats did not display more open-arm activity as maze height decreased. In Experiment 5, height cues were manipulated by placing a "floor" 8 cm beneath one open arm while leaving the floor of the other open arm at 50 cm. Rats did not avoid the "low" open arm less than the "high" open arm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446681 TI - Effects of alprazolam on intravenous cocaine self-administration in rats. AB - The specificity of benzodiazepine pretreatment on the reinforcing efficacy of cocaine was investigated using a multiple schedule of cocaine and food presentation. Cocaine was available under a fixed-ratio 4 schedule of reinforcement during 1 h of the session, while food was delivered under a discrete-trial, fixed-ratio 10 schedule during the other. Following initial exposure to alprazolam, responding maintained by both cocaine and food was significantly reduced. However, tolerance quickly developed to the sedative effects of alprazolam on food-maintained responding, while no reduction in the effects of the drug on cocaine self-administration was observed. Alprazolam (0.5 to 4.0 mg/kg, IP) significantly reduced cocaine intake without affecting food maintained responding following subsequent testing with the drug. These data suggest a potential specific effect (e.g., anxiolytic) of alprazolam in cocaine reinforcement. PMID- 8446682 TI - Repeated testing within drug discrimination learning: time course studies with cocaine, amphetamine, and 3-PPP. AB - Pigeons were trained to discriminate between 3 mg/kg cocaine and saline. Tests with cocaine and amphetamine were conducted at different intervals after administration to compare the time course of the discriminative stimulus (DS) effects. Tests were of two kinds: a) separate, that is, only one dose and interval were examined on each separate test day; and b) repeated, that is, all three intervals were assessed after a single administration of the drug dose during 1 test day. Separate and repeated determinations of the time course yielded similar estimates. The duration of the DS effects of amphetamine were longer than those of cocaine. No apparent difference, either with regard to duration of effect or potency, existed between (+)- and (-)-amphetamine. The potency of cocaine was similar to that of the amphetamine isomers. The dopamine autoreceptor blockers (+)- and (-)-3-(hydroxyphenyl)-N-n-propylpiperidine (3-PPP) (1-10 mg/kg) engendered less than 44% cocaine-associated responding for the repeatedly examined intervals (15, 60, and 120 min after administration). The results of this study encourage the use of repeated testing methodology to assess the duration of action of the DS effects of drugs. PMID- 8446683 TI - Spatial learning deficit and reduced hippocampal ChAT activity in rats after an ICV injection of streptozotocin. AB - ICV injections of streptozotocin (STREP) lower the glucose utilization of the brain and affect the cholinergic system. The present study was designed to evaluate whether STREP-treated rats have an impaired spatial discrimination performance in the Morris spatial navigation task. Performance in this task is sensitive to treatment with cholinergic antagonists. In contrast to young rats, middle-aged STREP-treated rats tended to have an impaired spatial discrimination performance in the Morris task at the end of training. In middle-aged STREP treated rats, but not in control rats, spatial discrimination performance was associated with hippocampal choline acetyltransferase (ChAT) activity. The correlation between spatial discrimination performance in the Morris task and the decrease in hippocampal ChAT activity resembles the relation between cognitive and biochemical changes observed in Alzheimer's disease. Our findings suggest that STREP treatment of middle-aged rats may provide a relevant model for dementia. PMID- 8446684 TI - Impaired acquisition in a 14-unit T-maze following medial septal lesions in rats is correlated with lesion size and hippocampal acetylcholinesterase staining. AB - Septohippocampal cholinergic system involvement in acquisition of an aversively motivated 14-unit T-maze was evaluated in 4-month-old male Fischer-344 rats. Each rat was assigned to one of two groups that received either a bilateral electrolytic lesion to the medial septal area (MSA) or a sham operation. One week after surgery, each rat began pretraining in one-way active avoidance (footshock = 0.8 mA) consisting of 10 trials per day on each of 3 consecutive days. Criterion for successful completion of pretraining was 8/10 avoidances on the third day. On the day following completion of pretraining, each rat received 10 trials in a shock-motivated 14-unit T-maze. The performance requirement was to move through each of five maze segments within 10 s to avoid footshock (0.8 mA). A second 10-trial session was provided 24 h later. Performance measures included errors, alternation errors, runtime, shock frequency, and duration. Following maze training, each rat was sacrificed, and formalin-fixed brains were frozen for histology, which included procedures for thionin Nissl and acetylcholinesterase (AChE) staining. MSA-lesioned rats were observed to be significantly impaired on all measures of maze performance compared to sham-operated controls. Densitometric analysis of hippocampal AChE staining revealed a 30% reduction in relative AChE staining of MSA-lesioned rats compared to sham-operated controls. Lesion size was observed to be highly positively correlated with maze errors. A negative correlation of mean error score with density of AChE staining was observed for MSA-lesioned rats, but not for sham-operated rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446685 TI - Patterns of body temperature during feeding in rats under varying ambient temperatures. AB - Relationships between feeding and body temperature of rats were investigated at three ambient temperatures during the whole light/dark cycle. Basal liver temperature was negatively correlated with ambient temperature. Only at 29 degrees C liver temperature indicated activation of autonomic and locomotory thermoregulatory responses due to heat stress. At 21 degrees C, liver temperature was always higher than skin temperature. Both showed a clear circadian rhythm with higher values during the dark phase. Meal-associated temperature patterns were superimposed on this circadian rhythm. Liver and skin temperatures showed a preprandial and prandial rise. Liver temperature reached an almost similar peak value just above 39 degrees C at the end of a meal, irrespective of meal size and ambient temperatures of 13 degrees C and 21 degrees C. Liver temperature reached this peak about 2 min earlier and dropped sooner than skin temperature. These results indicate a threshold liver temperature at which feeding activity stops. The present study suggests that temperatures do not exceed this value by adaptive autonomic thermoregulatory responses shifting heat flow from core to skin and by stopping all locomotory activities including feeding, thereby avoiding deterioration of vital organs and physiological processes due to hyperthermia. PMID- 8446686 TI - Androgenic induction of brain sexual dimorphism depends on photoperiod in meadow voles. AB - Male meadow voles maintained in a long photoperiod (LP) from birth have heavier brains than do females, but in short photoperiods (SP) this sex dimorphism is absent. Testosterone propionate (TP) administration on the second day of postnatal life produced significant increases in brain weight of LP but not SP females at 35 days of age. Short daylengths reduce the responsiveness of the meadow vole nervous system to the masculinizing effects of perinatal testosterone and may, in part, mediate the seasonally reduced sex difference in brain weight. PMID- 8446687 TI - Nervus terminalis lesions: I. No effect on pheromonally induced testosterone surges in the male hamster. AB - The involvement of the nervus terminalis or terminal nerve in the pheromonally induced testosterone surge in the male hamster was investigated. Blood was collected from male hamsters not exposed to odor (baseline), and then a week later from the same hamsters exposed to the odor of vaginal discharge from an estrous female. Terminal nerve lesions, forebrain lesions, or sham surgeries were performed, and blood was collected again with and without odor stimulation. Serum testosterone levels were assessed by radioimmunoassay. None of the surgical procedures interrupted the ability of the male hamsters to demonstrate an increase in serum testosterone following exposure to the odor of an estrous female. We conclude that the terminal nerve is not necessary for this pheromonally mediated neuroendocrine reflex. PMID- 8446688 TI - Twenty-four hour rhythms of selected ambient temperature in rat and hamster. AB - The purpose of this study was to assess the effect of time of day on the behavioral thermoregulatory patterns of nocturnal rodents, the Long-Evans (LE) rat, Fischer 344 (F344) rat, and the golden hamster. Individual animals were placed in a temperature gradient for 4 days while selected ambient temperature (STa) and motor activity (MA) were monitored. Food was provided at the cold and warm ends of the gradient and water was provided ad lib. All animals eventually showed a 24-h rhythm of STa and MA characterized by a preference for cooler TaS during the dark period which coincided with an increase in MA. Both rat strains had STaS of approximately 28 degrees C during the light period that decreased to 22-24 degrees C during the dark period. The F344 rat developed a STa rhythm by the second day in the gradient, whereas the LE strain required 4 days. The hamster exhibited relatively warm STaS of 32-33 degrees C during the light period that decreased to 26-28 degrees C during the dark period. The nocturnal preference for cooler STaS contradicts a current concept of an elevation in set point of the thermoregulatory system. However, the data also suggest that behavioral and autonomic thermoregulatory effectors may operate independently in the control of night time elevations in body temperature. PMID- 8446689 TI - Control of physical exercise of rats in a swimming basin. AB - To study the mutual interaction between physical exercise and antioxidant systems in rats, we selected swimming as a model for exercise performance. Swimming belongs to the natural behavior of a rat, which under proper experimental conditions, primarily involves physical exercise with little emotional arousal. Therefore, we developed a swimming basin in which the intensity of exercise was manipulated by swimming speed and swimming duration. A laser beam interruption system enables recording of swimming patterns. For comparison we also used the basin to induce emotional arousal. Hereto the basin was transformed into a maze, in which unexpected blockade of a learned swimming route induced a panic-like emotional reaction. The antioxidant enzyme superoxide dismutase decreased in rat plasma after emotional arousal, not after physical exercise. Depletion of the antioxidant glutathione in the liver by diethyl maleate led to decrease of swimming performance. Noradrenaline but not adrenaline plasma levels increased in response to physical exercise. After emotional arousal the ratio noradrenaline/adrenaline did not change. In contrast, lactate only increased in response to emotional arousal. Plasma levels of glucose increased after both stress situations. Beta-adrenoceptor function, determined in the heart and in erythrocytes, only changed after physical exercise. The sensitivity to the beta agonist (-)isoprenaline in the right atrium decreased and a downregulation of the beta-adrenoceptor density was observed in the erythrocyte. PMID- 8446690 TI - Concentration-dependent licking of sucrose and sodium chloride in rats with parabrachial gustatory lesions. AB - The medial zone of parabrachial nuclei (PBN) serves as an obligatory synapse in the central gustatory system in rodents. Lesions in the PBN impair taste aversion learning and depletion-induced sodium appetite in rats, and also alter the ingestion of sapid stimuli. Interpretation of these lesion-induced behavioral deficits requires an evaluation of whether taste function is compromised. The present study examined whether rats with PBN lesions could show normal concentration-dependent changes in licking behavior to very small volumes of NaCl and sucrose. Physiological state was also varied; taste responsivity was examined in water-deprived and nondeprived rats. In a specially designed gustometer, nine rats with electrophysiologically guided lesions in the PBN and five surgical controls were trained to lick a drinking spout to receive 10-s access to various concentrations of NaCl (0.03-1.0 M) and sucrose (0.01-1.0 M) during 30-min sessions. Water-deprived control rats progressively decreased their responses compared with water as the concentration of NaCl was raised. In contrast, water deprived PBNX rats did not decrease their licking responses to NaCl relative to water until the concentration reached 1.0 M. In the nondeprived state, control and PBNX rats decreased their responsiveness as a function of NaCl concentration, and the two groups did not differ. The licking responses of water-deprived PBNX rats did not differ from control rats when sucrose was the stimulus. In the nondeprived condition, both groups monotonically increased their licking to sucrose as a function of concentration, but PBNX rats were significantly less responsive than controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446691 TI - Jaw movements and EMG activities of limb-licking behavior during grooming in rabbits. AB - Jaw movements and masticatory muscle activity were recorded in freely moving rabbits during limb-licking, chewing, and drinking. The limb-licking movement was characterized by rhythmical jaw movement and digastric burst and relatively small masseter activity. The mean cycle time was 292 ms +/- 11.0 (mean +/- SE: n = 7) and was longer than that in chewing (267 ms +/- 20.8, p < 0.01) or drinking (208 ms +/- 15.2, p < 0.01). Jaw movements in the frontal plane of the ingestive behaviors coincided with those reported in previous studies; however, that of the licking movements was featured here. The basic cycle included; a) an opening stroke in which the mandible moved downward and laterally, b) a lateral excursion stroke in which the mandible moved medially and either upward or downward, and c) a closing stroke in which the mandible moved upward to the closing position. During opening, the digastric activity on the working side was determined to be larger than that on the other side (p < 0.001). PMID- 8446692 TI - In utero release from a single transient hypoxic episode: a positive reinforcer? AB - In this experiment, fetal rats, Rattus norvegicus, were subjected to a single transient hypoxic episode before an injection of orange essence or isotonic saline through the uterine and amniotic membranes into the amniotic fluid within 5 s of the release from hypoxia. Other animals experienced either orange essence or isotonic saline alone following no hypoxic episode. At 120 days after birth, adult rats were given a two-choice preference test between orange and water. Only those animals who experienced the orange following release from hypoxia showed a preference for the orange. These results suggest that the acquired preference is not a result of simple exposure but is suggestive of a role for reoxygenation as a positive reinforcer. PMID- 8446693 TI - Learning of leg position by cockroaches in response to light. AB - Learning by the cockroach Periplaneta americana was studied using an electronic device that turns off a light in response to leg position. Training and testing were modeled on the Horridge procedure, with the position of a leg of one cockroach (P) controlling stimulation of both itself and a yoked control (R) during training, and the legs of P and R controlling stimulation independently during testing. In addition, testing was followed by reversal, in which each cockroach had to avoid the trained position in order to prevent exposure to light. During half-hour training periods. P cockroaches learned to lift a mesothoracic leg to turn off light. This learning was most evident during reversal, when P cockroaches continued to keep the leg lifted and were therefore exposed to appreciably more light than were R cockroaches. Cockroaches were unable to learn to lower the mesothoracic leg to escape light with a similar procedure. PMID- 8446694 TI - Effect of neonatal androgenization on the circadian rhythm of feeding behavior in rats. AB - The effect of neonatal androgenization with testosterone propionate (TP) on growth, food intake, and feeding circadian and ultradian rhythms was studied in male and female rats. TP-female rats but not TP-male rats weighed more and ate more in adulthood than control animals injected with oil. TP administration to male rats induced few changes in the circadian organization of food intake and meal size. However, neonatal androgenization of female rats produced an approach of feeding parameters to those showed by male rats: diminished meal number and increased meal size and food intake. Moreover, the spectral analysis of meal frequency revealed that TP induced in female rats an enlargement in the 4.8 h ultradian component. Although hormone secretions produced in adult animals contribute to sexual dimorphism, it is noticeable that androgen presence during the organizational period is largely responsible for differences between sexes. PMID- 8446695 TI - Hepatic vagotomy does not disrupt the normal satiation of NaCl appetite. AB - The necessity of the hepatic branch of the vagus nerve for the normal satiation of NaCl intake under the condition of sodium depletion was tested. Sham- or hepatic-vagotomized male, Long-Evans rats were sodium depleted by injection with Lasix (furosemide, 10 mg) and were maintained overnight on sodium-deficient diet and water. The intake of 0.3 M NaCl during a 2-h salt appetite test was not significantly different between the sham- and hepatic-vagotomized groups. In a second group of sham- or hepatic-vagotomized rats, a load of 7.5 ml of 0.5 M NaCl was given by gavage at 15 or 90 min prior to a 1-h NaCl appetite test. The preload decreased NaCl intake equivalently in both groups. Gastric emptying of a preload of NaCl at 15 and 90 min was also the same for sham- and hepatic vagotomized rats. Thus, the hepatic branch of the vagus nerve is not necessary for the normal short-term satiation of NaCl intake under the condition of acute sodium depletion produced by furosemide. PMID- 8446696 TI - Sickness behavior in birds caused by peripheral or central injection of endotoxin. AB - Recent evidence indicates that many of the physiologic, metabolic, and behavioral responses that accompany infection in mammals are important for maintaining homeostasis and promoting recovery. In the present report, we have extended this concept to birds by demonstrating that LPS injected IP reduces feed intake, increases somnolence, decreases plasma [Fe] and [Zn], increases plasma [Cu], and elevates plasma corticosterone. To determine if any of these effects could be mediated centrally, LPS was injected intracerebroventricularly (ICV). Whereas peripheral injection of LPS caused a modest increase in body temperature, the hyperthermic effect of LPS injected ICV was intense and long lasting. This hyperthermia following ICV injection of LPS was accompanied by only a transient reduction in food intake and elevation in somnolent activity, with no change in plasma [Fe] or [Zn]. Both peripheral and central injections of LPS increased plasma corticosterone, but the increase caused by peripherally administered LPS was sixfold higher than that caused by LPS injected centrally. Collectively, these data show that chickens respond to both peripheral and central injections of endotoxin by reducing food consumption, increasing somnolence, becoming febrile, and elevating plasma corticosterone. However, the magnitude of these responses depends upon whether LPS acts at central or peripheral sites. PMID- 8446697 TI - Facilitation of shuttle-box avoidance by the platform method: effects of conditioned stimulus duration. AB - To evaluate whether the duration of the conditioned stimulus (CS) influences the facilitatory effect of posttraining platform treatment upon the acquisition and long-term retention (LTR) of a shuttle-box conditioning, rats were assigned to one of the four following treatments: P-3 group rats were subjected to a 5-h treatment on 16 cm diameter platforms immediately after each of 5 training sessions (10 trials each separated by 24-h intervals) in which the CS consisted of a tone lasting 3 s; control-3 rats were trained the same way but were not subjected to the platform treatment; P-10 rats did also receive the immediate 5-h treatment on platforms, but the CS was a tone lasting 10 s; finally, control-10 rats did not receive any treatment and were also trained with a 10-s tone. Ten days after training, all rats were also tested for LTR (1 session of 10 trials). When the CS duration was 3 s, the platform treatment improved both the acquisition and LTR of the task, compared to control subjects, but the same treatment had no effect when the CS lasted 10 s. With the use of a 10-s CS, the level of learning achieved by both treated and untreated subjects was similar to the final level of acquisition reached by treated subjects trained with a 3-s CS. We conclude that the facilitatory effects of the platform method treatment upon the acquisition and LTR of a distributed shuttle-box avoidance depend on the difficulty of the task. PMID- 8446698 TI - Developmental consequences of diet and activity. AB - The effect of a protein-deficient and a protein-surfeit diet and continuous access to an activity wheel on food intake, growth, and body temperatures of behaviorally thermoregulating White Leghorn chicks was assessed in two experiments. In Experiment 1, both imbalanced-protein diets depressed intake and growth and differentially affected activity relative to a control diet, but activity did not ameliorate the deleterious effect of a high-protein diet on growth. Diet groups with continuous access to a running wheel did not differ on any measure from corresponding inactive dietary control groups. In Experiment 2, these results were replicated in a lower ambient temperature, and an effect of diet on body temperature emerged. Diets that affected spontaneous activity or body temperature also affected death feigning, a predation defense behavior. The data from behaviorally thermoregulating chicks are consistent with previous findings that activity does not depress growth rate in animals who cannot convert a portion of their intake into adipose tissue. PMID- 8446699 TI - Peripheral and central effects of CCK receptor agonists on operant feeding in pigs. AB - Operant feeding was recorded in 18 h deprived pigs after peripheral (IV) or central (ICV) administration of saline, the CCK A agonist A-71378, the CCK B agonist pentagastrin, or pentagastrin vehicle. In Experiment 1 (n = 10), A-71378 (0.5, 1.0, and 2.0 micrograms/kg) given IV produced a sustained dose-related reduction in food intake (p < 0.02), whereas the same doses of pentagastrin were without effect. In Experiment 2 (n = 10), neither agonist given ICV (1 microgram) had consistent effects on operant responding. A higher ICV dose of A-71378 (5 micrograms) was also ineffective, whereas 1 microgram CCK octapeptide given ICV inhibited feeding (p < 0.03). These findings suggest that A receptors outside the blood-brain barrier mediate the suppressant effect of IV CCK on feeding in the pig and that neither peripheral nor central B receptors influence food intake in this species. PMID- 8446700 TI - Rats discriminate between starch and other substances having a similar texture. AB - Studies examined the contribution of textural factors to the ability of rats to sense starch. If rats sense the abrasive effects of starch suspensions, conditioned aversions to starch should generalize to substances having a similar texture. Two substances having a texture similar to that of starch were examined, polymeric dialdehyde (a product derived from starch) and inulin (a polymer of fructose). Rats were trained to avoid dilute suspensions of rice starch, potato starch, polymeric dialdehyde, or dahlia inulin, by injecting them with lithium chloride after they drank the test substance. Generalization tests revealed that rats trained to avoid rice or potato starch subsequently avoided corn starch, whereas rats trained to avoid polymeric dialdehyde or dahlia inulin did not avoid corn starch. Rats trained to avoid polymeric dialdehyde avoided this substance to a greater degree than did rats trained to avoid rice or potato starch. Rats trained to avoid dahlia inulin avoided this substance to a greater degree than did the rats in the other groups, but avoidance of dahlia inulin did not generalize to chicory inulin. Untrained rats showed little or no preference for dilute suspensions of polymeric dialdehyde or inulin, but did prefer starch over vehicle. It is concluded that tactile sensitivity does not play a large role in the perception of dilute starch suspensions. PMID- 8446701 TI - Aggression by a female rat cohabiting with a sterile male declines within 27 h following ovariectomy. AB - Females that had become aggressive as a result of cohabiting with a sterile male were ovariectomized and implanted with empty Silastic tubes. Control groups were either sham ovariectomized or ovariectomized and implanted with Silastic tubes providing replacement levels of estradiol and testosterone. Twenty-seven hours following surgery, all animals were tested for aggressiveness toward an unfamiliar female rat. The aggression of ovariectomized females without hormone replacement declined to a minimal level postoperatively and was significantly lower than that of sham-ovariectomized females or ovariectomized females with estradiol and testosterone replacement. Both sham-ovariectomized females and ovariectomized females given hormone replacement displayed a level of aggression close to that observed preoperatively. The aggression of a female rat cohabiting with a sterile male appears to be highly sensitive to the removal of gonadal hormones. This corresponds with observations made on pregnant females and contrasts with those made on lactating females. PMID- 8446702 TI - Anxiety enhancement in the murine elevated plus maze by immediate prior exposure to social stressors. AB - Anxiety has been implicated in the acute nonopioid analgesic reaction seen in defeated mice. In the present study, behavioural responses to the elevated plus maze test were examined in male DBA/2 mice immediately following defeat by an experienced aggressive conspecific. Compared to home-cage controls, defeat reduced total arm entries and rearing, although anxiety enhancement was indicated by decreases in percent open-arm entries and percent time spent on the open arms. These effects were accompanied by significant increases in nonexploratory behaviour (movement arrest and grooming) and risk assessment (closed arm returns, protected head dipping, and stretch-attend postures). This anxiogenic effect of social defeat was partially replicated in mice merely exposed to the scent of an aggressive male conspecific. The specificity of present findings to socially relevant stressors was confirmed by the general lack of effect on plus-maze behaviour of prior exposure to a novel cage or to interaction with a nonaggressive male. Present results are not only consistent with the anxiety hypothesis of defeat analgesia but also show that the elevated plus-maze test is sensitive to alterations in anxiety produced by ecologically relevant stimuli. Possible implications for pharmacological studies are discussed. PMID- 8446703 TI - Sexual maturation and seasonal changes in plasma levels of sex steroids and fecundity of wild Norway rats selected for reduced aggressiveness toward humans. AB - Parameters of sexual maturation and reproductive function were compared in two groups of Norway rats, one selected for reduced aggressiveness towards man and the other for aggressiveness. It was found that selection for reduced aggressiveness produced an acceleration of sexual maturation as judged by earlier vaginal opening in the female and presence of mature spermatozoa in the testes of the male as well by earlier prepubertal increase in plasma testosterone in the male. In domesticated adults, seasonal variations in the parameters of the reproductive function narrowed; they showed neither the winter decrease in sexual activity nor the marked fall in plasma testosterone and estradiol exhibited by their aggressive counterparts. PMID- 8446704 TI - Effect of flavor enhancement of foods for the elderly on nutritional status: food intake, biochemical indices, and anthropometric measures. AB - The irreversible declines in taste and smell acuity that occur in many elderly persons can contribute to inadequate food intake and nutrition that are prevalent among the aged. Although chemosensory deficits cannot be reversed, previous studies have shown that the addition of intense flavors to foods can compensate for perceptual losses and improve food palatability and acceptance. In this study, the effect of sustained (3 week) flavor enhancement of typical institutional foods on the diet, health, and well being of 39 elderly (average age 84.6 SE 0.81 years) retirement-home residents was evaluated. For 3 weeks subjects ate an institutional diet (unenhanced). During another 3-week period, the same subjects ate identical foods to which intense flavors were added (enhanced). The 39 subjects were tested in two groups. For group 1 the unenhanced food period preceded the enhanced food period. For group 2, the order was reversed. Food intake was measured every weekday throughout the study, and the nutritional composition of the diet was analyzed. Biochemical measures of health status were obtained at the beginning of the study (baseline) and following both the unenhanced and enhanced periods. These measures included somatomedin C/insulin-like growth factor I, transferrin, total T- and B-lymphocytes, and routine blood chemistries. Weight, height, midarm circumference, and triceps skinfold thickness were also measured. Handgrip strength and pinch strength were measured in group 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446705 TI - Effects of acute treadmill exercise and delayed access to food on food selection in rats. AB - Total energy intake and macronutrient self-selection were examined in rats following forced exercise (2 h treadmill, 15 m/min) or after a similar period of food deprivation without exercise. Acute exercise was realized at the end of the daytime. Return to the home cage for food access after exercise or after the same period of fasting was delayed for 0, 30, and 90 min. It has been shown that rats decreased body weight after all exercise situations. Food intake after deprivation was decreased in the first 3 h but was not modified over 24 h. The 24 h energy intake after exercise was identically reduced in the three situations. Carbohydrate and protein intakes were significantly reduced just after exercise. Protein decrease persisted all through the night and, to a lesser extent, during the following nycthemere. Fat decrease appeared later and was significant in the last part of the night. Increasing the delay to food access after exercise did not modify the total energy intake, but it significantly reduced carbohydrate intake. Those results show that exercise has a longer influence on food intake and, specifically, on macronutrient selection, than just food deprivation. Various hypotheses regarding central (cerebral neurotransmitters) and peripheral factors could be evoked in order to explain these modifications in the self selected diet after an acute exercise. PMID- 8446706 TI - Male rats classified as copulators and noncopulators respond differentially on the hot plate test. AB - Sexually naive male rats that fail to copulate with a sexually receptive female (noncopulators) have been shown to be less responsive to a variety of environmental stimuli in comparison to rats that do engage in copulation (copulators). In this experiment, it was found that noncopulators were less responsive than copulators to noxious thermal stimulation as determined by their latency to paw lick on a 50 degrees C hot plate. Pain sensitivity was not influenced in either noncopulators or copulators by exposure to a sexually receptive female. These results add to the list of differences between copulators and noncopulators. PMID- 8446707 TI - A microstructural analysis of the effects of presatiation on feeding behavior in the rat. AB - Rats were familiarized with eating a sweetened mash, and were divided into three groups. Before a test meal, the animals were allowed to eat the mash for 0, 2.5, or 5 min, respectively, to vary the degree of their satiation. Their subsequent consumption of the meal and their behavior over the course of a 30-min period was observed, to provide a microstructural description of the behavioral changes that are characteristic of increasing satiation. Presatiation, as expected, reduced the size of the test meal, and did so predominantly by reducing the duration of feeding, especially during the first 5 min of the test period. There was a slight reduction in the rate of eating as a function of presatiation, and a tendency for the latency to initiate feeding to increase. When other responses were considered separately, there was little effect of presatiation on their microstructural parameters. However, the duration of a composite category (comprising rearing, grooming, and stationary) did increase significantly as a function of presatiation. These data provide a behavioral template for satiation, against which to compare treatments that purport to manipulate feeding satiation. PMID- 8446708 TI - Influence of stress on IgE production. AB - Intense acute stress, consequent to restraint, leads to a diminished production of IgE antiovalbumin antibodies in mice. The IgE content of sera from experimental or control animals was assayed by the enzyme-linked immunosorbent assay (ELISA) at days 8, 16, and 20 after immunization. The statistics revealed significant differences in the IgE level of the animals submitted to acute stress and home cage control animals on days 16 and 20 after immunization, but not on day 8. PMID- 8446709 TI - Human immunodeficiency virus status in facial fracture patients. AB - A prospective study was performed to obtain an indication of the incidence of human immunodeficiency virus (HIV) among the population of facial fracture patients treated at a city hospital in Toronto, Ontario, Canada. This study was stimulated by the observation that a significant number of the patients treated at this unit were drug and alcohol abusers, inmates of a local penitentiary (where homosexual activity is believed not to be uncommon) or had no fixed address. In addition, the surgical treatment of these patients involved the use of sharp, high-powered motorized instruments e.g., saws, drills, wires, etc., and resulted in the spillage and aerosolization of considerable amounts of blood and other tissues. Operating room staff are exposed to these patients for 12 to 18 hours on many occasions. Accidental exposure to body fluids can occur easily. It was thus decided to obtain consented HIV testing of all facial fracture patients managed by the Plastic Surgery Team between July and December 1990. Fifty-two patients were seen, and 47 (90.4%) of them were tested for HIV. Results were obtained for 46 (97.8%) of those tested. One patient (2.2%) was found to be positive for HIV. This figure was smaller than anticipated considering the patient population demographics, but is not an insignificant number and thus it is advised that if any suspicion arises, consented HIV testing should be obtained and the necessary precautions taken. PMID- 8446710 TI - A multiphase system bone implant for regenerating the calvaria. AB - The regeneration of bone with a biodegradable, biocompatible carrier and osteo regenerative proteins may be possible if the carrier has the appropriate architecture to support osteoconduction and prevent soft-tissue prolapse into ablated bone segments. Using radiomorphometry and histomorphometry, our group assessed individually and combined the components of a multiphase system bone implant (MSI) in rabbit cranial defects (critical-size defects: CSDs): two disks of biodegradable polymer (PLG) and demineralized bone matrix (DBM), a recognized osteo-regenerative material. We used 48 rabbits evenly divided between four treatment groups and two time periods. Six weeks after treatment, both DBM and PLG had significant positive effects on bone regeneration (based on a three factor analysis of variance, p < 0.05). These effects were synergistic when the components were combined (MSI). Defects treated with DBM or PLG alone continued to regenerate bone through 12 weeks. By this time, bone within the defects treated with MSI appeared to be maturing and consolidating. We conclude that the concept of placing osteo-regenerative factors between two biodegradable disks for regenerating segments of calvaria is viable. PMID- 8446711 TI - Fixed membranous bone graft survival after recipient bed alteration. AB - The effectiveness of membranous bone grafting in craniofacial reconstruction is hindered by resorption. The aim of this study was to determine whether alterations of the recipient bed through tissue expansion affect membranous bone graft survival. Eighteen adult rabbits were divided into three groups. Group I rabbits (control) received fixed autologous membranous bone grafts to their snouts. Group II rabbits had self-inflating tissue expanders inserted over their nasal dorsum, inflation for 3 weeks, and then expander removal and placement of fixed autologous membranous bone grafts to their snouts. Group III rabbits varied from group II by delaying bone grafting until 2 weeks after expander removal. One animal from each group was killed at post-grafting days 15 and 45, the remainder at day 90. Results were assessed by volumetric, nondecalcified histologic, and stereologic analysis. Volumetrically, group I grafts demonstrated 82 percent survival, whereas group II demonstrated 101 percent (p = 0.029) and group III 94.5 percent (p = 0.21). Histologically, group I grafts exhibited greater loss (i.e., porosity and resorption) and less labeling activity. Groups II and III showed extensive evidence of trabecularization and incorporation at the graft host interface. Stereologic measurements such as osteoid seam width (OSW) confirmed the greater survival and activity of groups II and III bone grafts. Group II OSW measured 12.4 microns, group III 12.0 microns, and group I 9.8 microns (p = 0.04). Stereology also demonstrated that groups II and III's OSW approached that of the recipient bed and contralateral zygoma, whereas group I did not (p = 0.029), suggesting an integration of the graft and host architectures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446712 TI - Vascularized osteochondral allografts in an immunosuppressed rat model: graft modulation and host immune tolerance. AB - The effects of 4 weeks of cyclosporin A (7 mg/kg per day) (CyA) on the survival of vascularized osteochondral grafts between rat strains [DA (donor) and Lewis (recipient)] and the presence and significance of host immune tolerance and graft antigen modulation after cessation of immunosuppression have been examined. Isografts (n = 12) survived without apparent abnormality for 8 weeks but showed signs of wasting after longer periods; unprotected allografts (n = 5) were rejected within 2 weeks. After 4 weeks of CyA, allografts remained healthy for at least 12 weeks but then deteriorated (n = 40). Antigen modulation was examined by graft removal at various intervals after cessation of CyA and reimplantation into a naive recipient (n = 14). All were rejected rapidly. Host tolerance was examined by graft removal at various periods after cessation of CyA and reimplantation of a fresh allograft (n = 15). Some of the second grafts survived at least 4 weeks without immunosuppression. The findings indicate development of incomplete host tolerance but no antigenic modulation of the graft. PMID- 8446713 TI - Hypertrophic tonsils: the effect on resonance and velopharyngeal closure. AB - This paper presents a case of altered resonance secondary to hypertrophic tonsils. Through nasopharyngoscopy, the tonsils were found to be in the nasopharynx and interposed between the velum and posterior pharyngeal wall. This resulted in incomplete velopharyngeal closure and evidence of hypernasality. This large mass was also felt to obstruct sound transmission into both the oral and nasal cavities, causing a mixture of hyponasality and cul-de-sac resonance. Tonsillectomy resulted in an elimination of all of these characteristics. Resonance was judged to be normal on the postoperative assessment. PMID- 8446714 TI - A modified palatopharyngeous flap operation and its application in the correction of velopharyngeal incompetence. AB - The conventional sphincteric pharyngoplasty does not achieve velopharyngeal competence in certain cases because of the intrinsic deficiency of the technique. A modified palatopharyngeous flap operation was introduced and used as a secondary procedure for the correction of velopharyngeal incompetence in 15 cleft palate patients. The results showed that the lateral-to-lateral connection and the high attachment of the palatopharyngeal flaps can form a new velopharyngeal port that is easily closed by velar movement. The surgical result is satisfactory, as revealed by the speech intelligibility test, videofluoroscopy, and nasopharyngoscopy. The surgical technique is described and the importance of presurgical identification of velopharyngeal movements is stressed in this paper. PMID- 8446715 TI - One-stage inferior labial flap and its pertinent anatomic study. PMID- 8446716 TI - Tissue expanders in the lower face and anterior neck in pediatric burn patients: limitations and pitfalls. AB - Radovan's 1982 landmark work on the clinical use of tissue expanders was felt to be a panacea for multiple reconstructive problems. We have used and probably overused tissue expanders for reconstruction of many complicated pediatric facial burn problems. This has enlightened us to some of the limitations of their use, and we have, therefore, reassessed our indications for their use. From 1984 through 1990, 52 tissue expanders were used in 37 pediatric patients for face and anterior neck burn scar resurfacing. This experience, combined with the unique problems encountered with face and neck tissue expansion, provided the groundwork for operative guidelines. The long-term effects of gravity, growth, and scarring on facial features adjacent to expanded skin led to the following principles. (1) Caution should be used in advancing expanded neck skin beyond the border of the mandible. The risk of scar widening or possible lip or eyelid ectropion needs to be considered when planning these flaps. Extreme overexpansion is necessary to advance unburned neck flaps over the mandibular border to avoid these problems. (2) After advancement or rotational flaps neck flaps to the face, vertically directed suture lines in the neck may need redirection to prevent linear contracture. This correction may be performed during the primary operation or during revisions. (3) Expanded cheek or neck skin should preferably replace burned areas, but at the same time, not violate unburned facial aesthetic units. (4) To counteract the affects of gravity, expanded cheek skin in conjunction with expanded neck skin, if unburned, may be the best choice for face or mandibular border scar replacement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446717 TI - Skin anatomy and antigen expression after burn wound closure with composite grafts of cultured skin cells and biopolymers. AB - Closure of large skin wounds (i.e., burns, congenital giant nevus, reconstruction of traumatic injury) with split-thickness skin grafts requires extensive harvesting of autologous skin. Composite grafts consisting of collagen glycosaminoglycan (GAG) substrates populated with cultured dermal fibroblasts and epidermal keratinocytes were tested in a pilot study on full-thickness burn wounds of three patients as an alternative to split-thickness skin. Light microscopy and transmission electron microscopy showed regeneration of epidermal and dermal tissue by 2 weeks, with degradation of the collagen-GAG implant associated with low numbers of leukocytes, and deposition of new collagen by fibroblasts. Complete basement membrane, including anchoring fibrils and anchoring plaques, is formed by 2 weeks, is mature by 3 months, and accounts for the absence of blistering of healed epidermis. All skin antigens tested (involucrin, filaggrin, laminin, collagens IV and VII, fibronectin, and chondroitin-sulfate) were expressed by 16 days after grafting. This cultured skin analogue provides an experimental alternative to split-thickness skin graft that develops histiotypic markers of skin anatomy and antigen expression after wound closure. PMID- 8446718 TI - Rhinoplasty: a practical guide for surgical planning. AB - A method for determining the aesthetically proportioned nasal length, tip projection, and radix projection in any given face is described. The proportioned nasal length is two-thirds (0.67) the midfacial height and exactly equal to chin vertical. Tip projection is two-thirds (0.67) the surgically planned or ideal nasal length. Radix projection, measured from the junction of the nasal bones with the orbit, is one-third (0.33) the ideal nasal length. The preferred clinical reference for measuring radix projection is the plane of the corneal surface; the radix projects 0.28 times the ideal nasal length from this surface (range: 9-14 mm). These-dimensional relationships were confirmed from direct clinical measurements taken from 87 models and subsequently applied in 126 consecutive rhinoplasties. The significance of this dimensional approach to rhinoplasty lies in the fact that planned nasal dimensions are based on facial measurements that allow the nose to vary in size directly with the face. Furthermore, it removes the dorsum as the primary focus in dimensional assessment. Rather, the dorsal prominence may be consistently described relative to a plane connecting the "ideal" radix and tip. PMID- 8446719 TI - Management of true ptosis of the breast. AB - A variation of the "Round Block" periareolar (Benelli) mastopexy is described which is applicable to breasts with true ptosis, the tubular breast deformity, and its lesser expressions. The characteristics of and differences between the various types of breast ptosis are reviewed. The thesis is set forth that: (1) The specific anatomic characteristics of true breast ptosis make this condition eminently treatable with a pursestring (modified Benelli Round Block) mastopexy. (2) The anatomic characteristics of other forms of breast ptosis require attention the pursestring mastopexy is not well adapted to. (3) Selection of procedures used to treat ptosis of the breast should be "type specific." PMID- 8446720 TI - Comparison between rapid and slow tissue expansion in breast reconstruction. AB - Fifty women scheduled for breast reconstruction surgery with tissue expansion were randomly divided into two groups. In the first group the tissue was expanded rapidly, i.e., once a day, starting 1 week postoperatively, and in the other group it was expanded slowly, i.e., once a week, starting after 2 weeks. The expansion periods were 14 and 41 days, respectively. In both groups the expansion volume was about 200% of the final breast prosthesis. The expanders were replaced by textured, gel-filled implants after 3 months. Follow-up examinations were made after 6 and 12 months to evaluate breast softness. A subjective method, Breast Augmentation Classification, and an objective method, applanation tonometry, were used and showed good correlation. Subjectively, the capsular contraction rate after 1 year was 33.5% in the whole series: 40% in the rapid expansion group and 27% in the slow expansion group. Objectively, the capsular contraction rate was 50.5% in all patients: 60% in the rapid group and 41.5% in the slow group. There was no statistically significant difference between the two groups at any time with either method. Irradiated patients included in the study did not show poorer results. The results obtained after 6 months remained stable up to 12 months after the implantation of the permanent prosthesis. The importance of objective evaluation to compare different series is discussed. PMID- 8446721 TI - The gluteal perforator-based flap for repair of sacral pressure sores. AB - A gluteal perforator-based flap employing the gluteus maximus muscle perforators located around the sacrum is described. A cadaveric study disclosed the existence of several significant perforators all around the gluteal region. Among these, the parasacral perforators originating from the internal pudendal artery and lateral sacral artery have proven useful for the repair of sacral pressure sores. A total of eight decubitus in seven patients were treated with gluteal perforator based flaps. There were no postoperative complications, such as flap necrosis and wound infection, with the exception of fistula formation in one case. This flap requires no transection or sacrifice of the gluteus maximus muscle, and elevation time for the flap is short. However, the perforators are located at various sites and thus require some careful dissection. PMID- 8446722 TI - Immunohistochemistry of fibronectin and actin in ungrafted wounds and wounds covered with full- and split-thickness skin grafts. AB - Fibronectin and actin content were measured with immunochemistry in excised wounds in 18 rats. In six rats, wounds were allowed to granulate and contract. Wounds were grafted with full-thickness skin in six rats and with split-thickness skin grafts in the remaining six. Multiple biopsies were taken for immunochemistry and electron microscopy. Actin and fibronectin content was greatest in ungrafted wounds. This content was reduced in wounds by skin grafting, with full-thickness grafts having a generally more inhibitory effect than split. In grafted wounds, actin was observed primarily in the wound bed, whereas fibronectin was present in both the wound bed and graft. Fibronectin appeared coincidently with actin in split-thickness skin grafts and their wounds. In contrast, full-thickness skin grafts had fibronectin staining before actin. The degree of wound contraction inhibition by different types of skin grafts appears to correlate with the fibronectin and actin staining patterns. PMID- 8446723 TI - Free toe transfer for thumb and finger reconstruction in 300 cases. AB - From 1966 to 1989, we performed free toe transfer for thumb and finger reconstruction in 300 patients, with 286 survivals and 14 failures, a total survival rate of 95.55 percent. Follow-up for 2 to 23 years showed that movement and sensation of the reconstructed thumbs and fingers were satisfactory in all of the 286 cases. The optimal indications for the operation were defect of the thumb at the plane of the metacarpophalangeal joint and defects of the second to fifth fingers. Besides atraumatic isolation of the second toe and sophisticated microsurgical suturing technique, special attention was paid to intraoperative vascular variations, to providing the double arterial blood supply system if necessary, and to the identification and management of postoperative circulatory crisis. PMID- 8446724 TI - Male to female surgery: a new contribution to operative technique. PMID- 8446725 TI - The significance of venous drainage in free flap transfer. AB - A skin flap in the anterior abdominal wall of the S-D rat was designed so that it was supplied by the superficial epigastric branch of the femoral artery on the right side. Venous drainage was effected through one of five designs: (1) the superficial epigastric vein on the same side, (2) the lateral abdominal vein on the same side, (3) the lateral abdominal vein on the opposite side, (4) the superficial epigastric vein on the opposite side, or (5) a combination of the latter three. Seventy-seven rats were available for final analysis. The surviving percentage area of the flap was found to improve with increased venous drainage and when the arterial blood had to traverse the flap to reach the diagonally situated draining vein. The use of venae commitante as the draining vein is not satisfactory. PMID- 8446726 TI - Reflections on two generations in plastic surgery. PMID- 8446727 TI - Simultaneous construction of an internal and external nose in an infant with arhinia. AB - We report on the simultaneous construction of an internal and external nose in an infant born with arhinia. The indication for this very early reconstruction was due to respiratory distress and the associated feeding problems. It was possible to create two nasal cavities separated by a septum and to form an external nose from pre-expanded skin and a secondary arm flap for the tip supported by a frontal bone flap with intrinsic growth potential and auricular cartilage grafts for the tip. The 4-year-old child has excellent function of the nose with an acceptable appearance. Her psychological development is normal. Respiratory distress and associated feeding problems necessitated the use of oropharyngeal and orogastric tubes in a female infant born without a nose (arhinia). Over a period of many weeks, with attempts to remove the tube resulting in aspiration, we decided to create a functional nasal airway and an external nose simultaneously at this early stage. At the age of 20 weeks, two nasal cavities were created by using a buccal sulcus incision and connected to the existing nasopharynx and partially lined with split skin grafts. An external nose was created using the expanded midfacial skin and supporting it, an osteoperiosteal flap from the frontal bone. Later, a Tagliacozzi flap had to be added for the nasal tip. The newly constructed nose functions well and appears to aid favorably in the normal psychosocial development of the now 4-year-old girl. PMID- 8446728 TI - Traumatic pseudoaneurysm in an ulnar artery vein graft. AB - Ulnar artery thrombosis is well reported but treatment recommendations still vary. We report the 10-year follow-up of a vein graft used to treat a patient with ulnar artery thrombosis. The graft remained patent until the tenth year, when the patient sustained a blunt hyperextension injury to the involved wrist and developed a pseudoaneurysm of the vein graft. The pseudoaneurysm was found to be in the graft itself and not at the anastomosis. The vein graft thrombosed and was successfully treated with resection of the thrombosed vessel, embolectomy of the superficial palmer arch, and replacement with a new vein graft. PMID- 8446729 TI - Heel replantation and subsequent analysis of gait. AB - A case of sharp, complete amputation of the heel with successful replantation is presented. The bones, periosteum, tendons, and neurovascular bundle were repaired. Seventeen months after injury, both motor and sensory recovery were satisfactory. The objective study of gait analysis also revealed an essentially normal gait pattern of the injured foot. These results suggest that in a suitable candidate, the procedure of choice for amputation of the heel is microsurgical replantation. PMID- 8446730 TI - The anatomic data sheet in plastic surgery: graphic and accurate documentation for standardized evaluation of results. AB - A graphic and written anatomic data sheet (ADS) for facial aesthetic surgery and body contour surgery is presented as a tool for: (1) analyzing surgical maneuvers and their effect on final outcome; (2) recording individual anatomic variations; (3) communicating data between office personnel and colleagues; (4) aiding in the treatment of the postsurgical patient; (5) use as a worksheet for the surgeon; and (6) standardizing, evaluating, and comparing surgical techniques. The ADS takes account of the common aesthetic facial and body contour procedures performed in plastic surgery. A supplemental rubber stamp for use on the office chart, with graphics identical to those of the ADS, identifies areas of treatment concern before and after surgery. PMID- 8446731 TI - Rigid fixation of mandibular osteotomies by an intraoral approach: technique and instrumentation. PMID- 8446732 TI - A simple technique for maintaining digital hypothermia during replantation surgery. AB - A simple technique using inexpensive and readily available materials is described for maintaining digital hypothermia during replantation surgery. Direct contact between soft-tissues and ice or water is prevented, and, thus, avoids undesirable maceration and also reduces the risk of cold-thermal injury, which would further prejudice the success of replantation. The technique is intended for use during prolonged replantation procedures, for example, in cases of trans-metacarpal amputation requiring revascularisation of more than one digit. The principle of using a water-tight sleeve could easily be extended to more proximal amputations, such as at the level of the wrist, by placing the entire hand within a double glove sleeve. PMID- 8446733 TI - Venous flaps. AB - One of the earliest postulates concerning the physiological basis of flap survival is attributed to Sushruta, who, in his inimitable style, very succinctly noted in Sanskrit verse the following words: "through continuity survives." Sanskrit being a very telegraphic language, what derives from these words is as follows: Through (the flap's) continuity (with its original location) (it) survives. The principle of continuity has survived through the ages, though continuity has come to imply vascular continuity based on the Harvesian model of circulation. No matter how we classify flaps, i.e., random or axial, the Harvesian model of circulation is the key to the mechanism of survival. Lately, however, a new category of flaps, that is, "venous flaps," have been reported by a number of investigators where the classical Harvesian model is not in evidence, at least apparently. The following effort is directed toward presenting the existing data on this subject for future guidance in research and clinical applications. PMID- 8446734 TI - Early free-flap coverage of electrical and thermal burns. PMID- 8446735 TI - Successful autologous fat injection at 5-year follow-up. PMID- 8446736 TI - The return of the case report to Psychosomatic medicine. PMID- 8446737 TI - Low vagal tone and antral dysmotility in patients with functional dyspepsia. AB - Effects of acute mental stress on gastric antral motility were investigated in 23 healthy persons and 25 patients with functional dyspepsia (FD). Real-time ultrasonography of gastric antrum was recorded, after ingestion of 500 ml meat soup, during a 4-min resting period, 2.5 min of mental stress, and a 4-min recovery period. Amplitude of antral contractions was scored as a fraction of relaxed area. Motility-index was calculated as the amplitude multiplied by frequency. Measurement of skin conductance reflected sympathetic tone, and respiratory sinus arrhythmia (RSA) was calculated to index vagal tone. Antral motility was reduced by mental stress in the healthy persons, but not in FD patients. Group differences were significant for amplitude (p < 0.002) and motility-index scores (p < 0.02). Sympathetic tone increased during stress in both groups. Vagal tone was lower in the FD patients than in the healthy controls (p < 0.001). The lack of stress-related reduction of motility among patients with FD may, therefore, be a consequence of poor vagal tone. PMID- 8446738 TI - Hostility and myocardial ischemia in coronary artery disease patients: evaluation by gender and ischemic index. AB - Two studies assess relationships of hostility to extent and severity of exercise induced cardiac ischemia and daily life ischemia in patients with coronary artery disease (CAD). CAD patients (N = 80) who underwent exercise tomographic thallium testing to assess myocardial perfusion completed the Cook-Medley Hostility Inventory (Ho). A Composite Hostility (Chost) score obtained from the Ho scale was also used. Statistically controlling for the effects of gender in the full sample (N = 80), Chost was positively correlated with severity of perfusion defects (r = 0.22, p < 0.05). This relationship was nonsignificant in the 63 male patients, but was significant among women (N = 17, r = 0.42, p < 0.05) and among middle-aged men (less than 60 years, N = 17, r = 0.55, p < 0.05). In an overlapping sample of 42 CAD patients with ischemia (ST-segment depression > or = 1 mm) during 24 to 48 hours of ambulatory electrocardiographic monitoring, after controlling for gender, both Ho and Chost were positively correlated with total minutes of ischemia (r = 0.28 and r = 0.29, respectively, p < 0.05). In addition, there was a significant gender x hostility interaction, with stronger relationships with hostility evident for women. Results from these two studies indicate that in patients with coronary artery disease, hostility traits are significantly correlated with extent of daily life ischemia and with severity of exercise-induced myocardial ischemia. These relationships appear to be significant among female and middle aged male patients, but may be less evident among older male patients. PMID- 8446739 TI - Lack of social support and incidence of coronary heart disease in middle-aged Swedish men. AB - Lack of social support has been found to predict all causes of mortality in population studies. It has often been assumed that the lack of social ties is associated with the general social conditions related to mortality and has little to do with specific disease etiology. So far, the association between lack of support and cardiovascular disease incidence has not been demonstrated. We have measured both emotional support from very close persons ("attachment") and the support provided by the extended network ("social integration"). This measure was applied along with standard measures of traditional risk factors to a random sample of 50-year-old men born in Gothenborg in 1933. All men (n = 736) were followed for 6 years and the incidence of myocardial infarction and death from coronary heart disease (CHD) was determined. Both "attachment" and "social integration" were lower in men who contracted CHD, with a significant effect for social integration (p = 0.04) and an almost significant effect for attachment (p = 0.07). When controlling for other risk factors in multiple logistic regression analyses, both factors remained as significant predictors of new CHD events. Smoking and lack of social support were the two leading risk factors for CHD in these middle-aged men. PMID- 8446740 TI - Hypertension affects neurobehavioral functioning. AB - This study compared the neurobehavioral performance of hypertensive and normotensive men and women using neuropsychological, information-processing, and psychometric assessments. One hundred subjects, including 68 hypertensive and 32 normotensive individuals, completed a test battery that yielded scores on measures of speed of information processing, verbal and figural memory, psychosocial functioning, Type A behavior, and locus of control. Results showed that, compared with the normotensive individuals, the hypertensives performed more poorly on a set of tasks that measure speed of information processing and short-term memory (Digit Symbol, Digit Span (Backwards), and Reaction Time (slope)). The hypertensives also reported higher levels of state anxiety relative to their normotensive counterparts. The effects of hypertension on neurobehavioral functioning could not be accounted for on the basis of age or education. PMID- 8446741 TI - Hypertension affects neurobehavioral functioning: so what's new? PMID- 8446742 TI - The association between daily blood pressure and catecholamine variability in normotensive working women. AB - Using ambulatory blood pressure monitors and timed urine collection techniques, blood pressure and the rates of urinary catecholamine excretion were compared across the work, home, and sleep environments of 45 women who perceived their work environment as most stressful (work stressed) and 35 women who perceived their home environment as equally or more stressful (home stressed) on the day of monitoring. The work-stressed women had higher systolic pressure at work (121 vs. 115; p < 0.05). There were no significant differences in diastolic pressure or the absolute levels of the catecholamines between the groups. However, the percent changes in blood pressure and catecholamines from work or home to sleep were significantly correlated in the work-stressed but not the home-stressed women (r values from 0.25 to 0.45, p < 0.05). The work-stressed and home-stressed women differed in their proportional make-up of several demographic characteristics, including having children (percentage of home-stressed women with children > work-stressed) (p < 0.05), ethnicity (percent of black home stressed > work-stressed) (p < 0.01), and family history of hypertension (percentage of work-stressed > home-stressed) (0.05 < p < 0.10). These differences, in part, may have determined the daily patterns of perceived stress in the two groups of women. Overall, these findings suggest that work stress and/or the sociodemographic characteristics that may influence the perception of work stress may drive a daylong sympathetic response that increases blood pressure in working women. PMID- 8446743 TI - Psychological, cardiovascular, and endocrine changes during 6 hours of continuous infusion of epinephrine or norepinephrine in healthy volunteers. AB - Psychological, cardiovascular, endocrine, and metabolic reactions to a sustained infusion of epinephrine (E) and norepinephrine (NE) were studied in 10 healthy male volunteers in a placebo-controlled randomized design. The subjects participated each in three sessions during which they received 6-hr infusion of either E (82 pmol/kg/min), NE (178 pmol/kg/min), or placebo (PLA) (saline, 5.4 ml/hr). Heart rate and intra-arterial blood pressure were recorded continuously. Blood samples for assay of catecholamines, cortisol, prolactin, growth hormone, insulin, triglycerides, and glucose were obtained at regular intervals. Changes in subjective mood were assessed with the Profile of Mood States (POMS) and the State-Trait Anxiety Inventory (STAI). During infusion of E, arterial plasma epinephrine levels increased 10-fold, which induced significant increases in heart rate, plasma insulin, and glucose levels, and decreases in mean arterial pressure (MAP) and diastolic pressure (DAP). NE infusion caused a 5-fold arterial plasma norepinephrine increase and induced a significant decrease in heart rate and increases in MAP, DAP, and glucose levels. The effects were present shortly after initiation of the infusions, remained fairly constant during the 6-hr infusion period and disappeared within 1 hr after the infusions had been stopped. Changes in subjective mood were not observed during the infusions, nor after the infusions had been stopped. Infusion of E or NE also had no significant effect on systolic blood pressure, plasma prolactin, growth hormone, cortisol, and triglycerides. Our results show that moderate cardiovascular and metabolic effects can be caused by sustained increases in circulating catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446744 TI - Mood and body weight in a woman with rapid cycling bipolar disorder: a case report. AB - To describe the relationship between mood and body weight, we analyzed 122 consecutive days of data from a 52-year-old woman with rapid cycling bipolar disorder, type II. The patient completed a daily log of self-reported mood, and weighed and recorded her weight daily. Mood and body weight were highly correlated (r = 0.60), and a decrease in mood preceded a decline in body weight by 3 days. Reports of loss of appetite on the Hamilton Depression Rating Scale also corresponded to periods of weight loss. There was a negligible difference in the patient's resting metabolic rate between a period of depression (1628 kcal/day) and of euthymia (1724 kcal/day). The association between depression and weight loss was primarily mediated by decreased food intake. Such patients should provide an excellent opportunity to study the regulation of body weight with affective illness. PMID- 8446745 TI - Ethnicity, family history of hypertension and patterns of hemodynamic reactivity in boys. AB - This study compared blood pressure, heart rate, stroke volume, vascular resistance, and cardiac output responses to a video game challenge and forehead cold stressor in 6- to 15-year-old males who varied in ethnicity and family history of essential hypertension. Controlling for age, significant baseline differences were obtained with black boys exhibiting higher systolic and diastolic pressures than their white cohorts. Positive family history children were found to have higher cardiac outputs and stroke volumes indexed by body surface area during baseline. Controlling for baseline hemodynamic responses and age, positive family history children exhibited greater increases in systemic vascular resistance and systolic and diastolic pressure and greater decreases in heart rate to the cold stressor. The positive family history children exhibited greater decreases in cardiac index during both the video game and cold stressor phases. Implications of the findings and directions for future research are discussed. PMID- 8446746 TI - Cardiovascular reactivity in anger-defensive individuals: the influence of task demands. AB - This study examined whether the elevated cardiovascular response to stressful stimuli previously suggested for individuals who are defensive in their reporting of anger might be moderated by the demands of the stressor task. Forty male undergraduates were exposed to four tasks: shock avoidance video game, handgrip, film, and cold pressor. Employing cluster analysis, defensive/low anger subjects were identified by high scores on the Marlowe-Crowne Social Desirability scale and low scores on the Spielberger Anger Expression and Trait Anger questionnaires. These individuals exhibited elevated heart rate and systolic blood pressure responses as compared with other subjects, but only to the shock avoidance task. Defensive/low anger subjects also reported less state anger to all tasks. It is proposed that an anger defensive style results in elevated cardiovascular activity only in interaction with stressors that elicit a sympathetic nervous system response and/or involve evaluation threat. PMID- 8446747 TI - Lactate infusion induces panic attacks in patients with premenstrual syndrome. PMID- 8446748 TI - Cartilaginous bone tumors. AB - Cartilaginous tumors can be subdivided into several categories according to the following three criteria: (1) Is the lesion benign or malignant? (2) Is the lesion a pure or impure cartilaginous tumor? (3) Is the epicenter of the lesion intraosseous, juxtacortical, or in the soft tissues? This article focuses on the four most common benign cartilaginous tumors, enchondroma, osteochondroma, chondroblastoma, and chondromyxoid fibroma, and on chondrosarcoma. It reviews the biologic and developmental considerations of each and discusses in depth the basic concepts in the radiologic diagnosis of cartilaginous tumors. PMID- 8446749 TI - Osseous lesions. AB - This article focuses on major clinical and imaging features that are of practical interest in diagnosis and management of bone forming neoplasms. Current histologic classification of these tumors is emphasized. Data presented are based on files of 1400 patients who have osseous neoplasms. PMID- 8446750 TI - Fibrous lesions of bone. AB - Fibrous lesions of bone include entities with a wide range of radiographic appearance and clinical behavior. Many benign fibrous lesions, such as medial supracondylar defects, fibrous cortical defects, and nonossifying fibromas have typical radiographic appearances and usually are self-limited. Desmoplastic fibromas and benign fibrous histiocytomas are less common, behave more aggressively, and usually require biopsy and surgical management. Fibrous dysplasia varies from solitary clinically unimportant lesions to wide-spread, deforming skeletal involvement that can lead to severe functional impairment and, rarely, even to death. Malignant fibrous lesions, including malignant fibrous histiocytomas and fibrosarcoma, produce aggressive lytic lesions, which require careful anatomic staging, accurate biopsy, and aggressive and appropriate treatment. PMID- 8446751 TI - Giant cell tumors of bone. AB - Giant cell tumor is a lesion that usually presents with a radiographically characteristic appearance in a predictable location and patient population. It has a few rare presentations such as pulmonary metastases and multifocal lesions. Prognosis of ultimate tumor behavior is dependent on surgical staging (which requires careful radiographic analysis to detect cortical breakthrough and joint involvement) and type of treatment. The recurrence rate is relatively high with simple curettage but decreases with adjuvant treatment at the tumor site. Optimal therapy for the more aggressive lesions is wide resection, but compromise is frequently required when such a resection would sacrifice joint function because of the subarticular location of the giant cell tumor. Radiation therapy is reserved for surgically inaccessible or otherwise inoperable lesions because of a relatively poor radiosensitivity and concerns about induction of high grade sarcomas. Radiographic follow-up evaluation for recurrence is recommended for approximately 5 years but may be difficult to interpret in individual patients because of an overlap in the appearance of healing and recurrence. PMID- 8446752 TI - Ewing's sarcoma. AB - Ewing's sarcoma is a highly malignant tumor of uncertain origin. A strong relationship is suggested between Ewing's sarcoma and tumors of neural origin. The radiologic manifestation of Ewing's sarcoma are protean and lesions may be lytic, mixed lytic-sclerotic, or rarely, predominantly sclerotic. The lower extremity long bones are predominantly affected and most lesions are diaphyseal or metadiaphyseal. CT and particularly MR imaging are invaluable in further delineating the extent of disease not readily manifested on plain radiographs. Gallium scintigraphy and gadolinium-enhanced MR images are best for following the response to therapy. Ewing's sarcoma must be distinguished from other round cell tumors including lymphoma, neuroblastoma, and primitive neuroectodermal tumor of bone as well as from osteosarcoma. PMID- 8446753 TI - Miscellaneous lesions of bone. AB - There are several tumors and tumorlike entities of bone that do not easily fit into the specific classifications provided elsewhere in this issue. In this article, several seemingly unrelated entities are discussed, including cystic diseases of bone (simple bone cysts and aneurysmal bone cysts), Langerhans' cell histiocytosis, benign and malignant vascular tumors of bone, and adamantinoma of long bone and its relationship to osteofibrous dysplasia. PMID- 8446754 TI - Imaging of soft tissue tumors. AB - In summary, MR imaging is the preferred modality for the evaluation of a soft tissue mass after plain films have been taken. The radiologic appearance of certain soft tissue tumors or tumorlike processes such as myositis ossificans, benign fatty tumors, intramuscular hemangiomas, pigmented villonodular synovitis, and certain hematomas may be sufficiently unique to allow a strong presumptive radiologic diagnosis. It must be emphasized that MR cannot reliably distinguish between benign and malignant lesions, and when radiologic evaluation is nonspecific, one is ill advised to suggest a lesion is benign or malignant solely on the basis of its MR appearance. CT may be useful in specific instances for the identification of subtle soft tissue mineralization in those patients in whom lesions are not adequately evaluated by radiographs. Ultrasonography may be useful in the assessing of recurrent disease as well as in establishing tumor vascularity. PMID- 8446755 TI - The histologic features of musculoskeletal tumors. AB - An atlas of 32 captioned color photomicrographs of typical musculoskeletal tumors is presented to demonstrate the need for close radiologic and pathologic correlation of these tumors. Diagnostic and key microscopic features of these soft tissue and bone lesions are highlighted. PMID- 8446756 TI - Magnetic resonance imaging of diffuse bone marrow disease. AB - MR is a highly sensitive alternative to plain films, CT, and radionuclide studies for the imaging of normal and abnormal marrow and can characterize differences between fatty, fibrotic, cellular, hypercellular, and hemosiderotic marrow. MR is helpful in depicting the extent of disease and has been a useful method to follow the clinical course of many disorders. It has been found to be particularly useful in explaining the unrepresentative biopsy, as the distribution of many diseases is frequently heterogeneous as exemplified by the mixed fatty and cellular patterns of aplastic anemia, myeloma, lymphoma, and skeletal metastases. Patterns of cellular and fatty marrow in the epiphysis and apophysis after marrow reconversion were not completely understood prior to the introduction of MR scanning. Because it has the advantage of imaging the entire bone marrow compartment (unlike the situation with biopsy on aspiration), MR allows a better understanding of the distribution of skeletal disease. PMID- 8446757 TI - Magnetic resonance imaging of primary skeletal neoplasms. AB - The primary role of magnetic resonance (MR) imaging of skeletal neoplasms is that of staging. Understanding the staging process and selection of the proper imaging planes and pulse sequences is essential for proper staging. To date, image features are not specific for histologic type. In addition, there are still pitfalls with MR imaging for evaluating recurrent tumor or following therapeutic response to treatment. Dynamic gadolinium studies and spectroscopy may improve the future overall specificity for MR imaging. PMID- 8446758 TI - Two-dimensional and three-dimensional computed tomographic imaging in musculoskeletal tumors. AB - Appropriate treatment of musculoskeletal neoplasms relies on prompt and accurate identification of tumor characteristics and extent. Multiplanar and three dimensional (3-D) computed tomography (CT) provide rapid, relatively noninvasive imaging for initial assessment and for planning of radiation therapy, en bloc resection, and limb-salvage surgery. An integrated 2-D-3-D CT approach also allows precise tracking of therapeutic response and recurrence. PMID- 8446759 TI - Arthropod eye design and the physical limits to spatial resolving power. PMID- 8446760 TI - Relationship between hippocampal opioid peptides and seizures. PMID- 8446761 TI - Prosopagnosia: a face-specific disorder. AB - A follow-up study of a patient, WJ with a very severe prosopagnosia is reported. After a stroke he became a farmer and acquired a flock of sheep. He learn to recognize and name many of his sheep, and his performance on tests of recognition memory and paired-associate learning for sheep was significantly better than on comparable tests using human face stimuli. It is concluded that in some instances prosopagnosia can be a face-specific disorder. PMID- 8446762 TI - Working harder for less: effect of incentive value on force of instrumental response in humans. AB - The present article reports evidence from human subjects that high payoff for instrumental performance may cause reduced vigour of response compared to the vigour observed for lower payoffs. Vigour of response, as measured by force of pressing (Experiment 1) and number of fortune wheel turns (Experiment 2), was inversely related to payoffs, with higher vigour in the low payoff conditions. Experiment 2 further demonstrated this effect, regardless of whether or not payoff depended on performance. These findings are related to parallel animal data, and an analysis in terms of a learned incentive-effort hypothesis is offered. Experiment 3 presented support for this hypothesis. The results are argued to be of importance to the understanding of how reinforcers affect human instrumental performance. PMID- 8446763 TI - Memory and metamemory performance in older adults: one deficit or two? AB - In two separate experiments, three groups of older adults (50-80 years old) were shown lists of forename-surname pairs. At test subjects were cued with the surname and asked whether they knew the forename (prospective evaluation). Subjects attempted recall for those items they claimed to know and rated their confidence in their answer (retrospective evaluation). In Experiment 1 subjects saw the name list on 5 successive occasions and attempted recall after each. The older subjects recalled fewer items, but there were no age differences on retrospective memory evaluation. There was a marginally significant age effect on the prospective memory evaluation, which on closer inspection appeared to be a scaling effect related to recall performance. Experiment 2 verified this conclusion in a sample of older adults taking part in a training study extended over many weeks. The main implication of this work is that studies that compare metamemory accuracy in groups that differ in baseline memory performance should be careful before drawing conclusions about metamemory independently of memory performance. PMID- 8446764 TI - An examination of the effects of axis foreshortening, monocular depth cues, and visual field on object identification. AB - Four experiments are reported on the identification of line drawings of common objects. In each experiment, performance on "unconventional" views of the objects, in which the major axis of the object was foreshortened, was compared to performance on more "conventional" views without appreciable foreshortening. In each experiment, except Experiment 2, where performance on the two views was experimentally equated, the foreshortened views were more difficult to identify than were the conventional views. Experiments 1 and 2 showed that if the foreshortened views were presented on a background with strong monocular depth cues, object identification was improved. This result suggests that part of the difficulty in identifying objects depicted from such a view stems from an improper depth interpretation of the object depictions. Experiments 3 and 4 examined visual field differences in the identification of the two types of object view. Results reported in the neuropsychological literature have shown that people with right-hemisphere damage have particular difficulty with the identification of unconventional views of objects that foreshorten major axes. Accordingly, it was expected that there would be a left visual field advantage for the foreshortened views. Neither experiment yielded any visual field effects consistent with this expectation. Possible reasons for the lack of a field effect are discussed. PMID- 8446765 TI - Hand preferences and hand ability in congenitally blind children. AB - Congenitally blind and sighted blindfolded children between the ages of 6 and 14 years were tested for hand preference with performance tasks. There were no differences between the groups in direction or degree of hand preference. The degree of handedness increased with age and was essentially linear though the blind seemed to be somewhat less lateralized at the younger ages. When the same groups were required to match three-dimensional bricks for height, depth, breadth, and volume, no hand advantages were found for either group. Both groups of children improved in their accuracy of spatial discriminations with age. Further, the degree of lateralization on the handedness task did not relate to ability on the tactile task or to differences between the right and left hands on the tactile task. Thus, there is no effect of blindness on tactile matching ability nor is there an effect of the hand used in the task. PMID- 8446766 TI - Saccadic eye movements and dual-task interference. AB - Four dual-task experiments required a speeded manual choice response to a tone in a close temporal proximity to a saccadic eye movement task. In Experiment 1, subjects made a saccade towards a single transient; in Experiment 2, a red and a green colour patch were presented to left and right, and the saccade was to which ever patch was the pre-specified target colour. There was some slowing of the eye movement, but neither task combination showed typical dual-task interference (the "psychological refractory effect"). However, more interference was observed when the direction of the saccade depended on whether a central colour patch was red or green, or when the saccade was directed towards the numerically higher of two large digits presented to the left and the right. Experiment 5 examined a vocal second task, for comparison. The findings might reflect the fact that eye movements can be directed by two separate brain systems--the superior colliculus and the frontal eye fields; commands from the latter but not the former may be delayed by simultaneous unrelated sensorimotor tasks. PMID- 8446767 TI - Bryodin, a single-chain ribosome-inactivating protein, selectively inhibits the growth of HIV-1-infected cells and reduces HIV-1 production. AB - Bryodin, a single-chain ribosome-inactivating protein (RIP) isolated from Bryonia cretica ssp dioica (cucurbitaceae), was found to selectively inhibit the growth of persistently HIV-1-infected T lymphoma cells (KE37/1) and human lung fibroblast when used in concentrations from 2-20 micrograms/ml. Uninfected KE37/1 cells remained unaffected at the same doses of bryodin. In addition, bryodin reduced HIV production in the surviving infected cells. Two isoforms of bryodin were purified by dye ligand chromatography. Both isoforms exerted the growth inhibiting influence and reduced HIV production. Trichosanthin, another member of the RIP family, had similar inhibitory effects on the growth of HIV-1 infected cells and on HIV-1 production. Bryodin and trichosanthin were effective in about the same dose range. No selective effects for HIV-infected cells were observed with the RIPs gelonin and ricin. PMID- 8446768 TI - Rat model for limb lengthening by callus distraction. AB - Limb lengthening and treatment of bone defects by using the method of callus distraction has become very important in traumatology and orthopedics. Despite increasing clinical use and ongoing research, many questions still remain unanswered. The biochemical processes that occur during matrix-induced bone formation have been elucidated, while the mechanisms of bone formation induced by callus distraction are still unclear. This study details the development of a new animal model in which rats undergo limb lengthening by callus distraction, offering the possibility of using modern immunological, and molecular biological techniques, which have already been developed for this animal species. The application of limb lengthening by callus distraction in this animal model has proven to be a practicable, reproducible, and economical procedure, which can increase our understanding of the callus distraction process. PMID- 8446769 TI - Glucose tolerance and insulin secretion in experimental pancreatic cancer in the Syrian hamster. AB - Pancreatic cancer develops at approximately 25 weeks after 6 weeks of weekly subcutaneous administration of N-nitrosobis (2-oxypropyl)amine in the Syrian golden hamster. We studied the glucose tolerance and insulin secretion during the development of pancreatic cancer in this model. Every 6th week after start of treatment, glucose was infused intravenously for 30 min (10 mg/min). It was found that the glucose tolerance and glucose-stimulated insulin secretion were normal at 6, 12, and 18 weeks after start of treatment compared with age-matched saline injected controls. By contrast, after 24, 30, and 42 weeks an exaggerated plasma glucose response and a concomitant impaired plasma-insulin response occurred during the glucose infusion (P < 0.05). We therefore conclude that the development of pancreatic cancer in this model is accompanied by glucose intolerance and impaired insulin secretion, and that these effects occur concomitantly with the development of cancer. PMID- 8446770 TI - Prevention of adhesions after laminectomy: an experimental study in dogs. AB - An experimental study was designed to compare the efficacy of Vicryl mesh and autogenous fat in minimizing postoperative epidural scar formation. Three-level noncontiguous laminectomies were performed on ten adult dogs. Exposed dura at the three levels was covered with (1) nothing (control group), (2) fat, and (3) Vicryl mesh. Animals were sacrificed 6 and 12 weeks postoperatively and the specimens were examined histologically. Compared with the use of free fat grafts after laminectomy in dogs, Vicryl mesh produced slightly more scarring, but consistently less than observed in controls. Although no surgical zone treated with Vicryl mesh exhibited evidence of neural compression, one of the ten fat grafted zones showed gross evidence of neural compression. These findings indicate that the use of Vicryl mesh at laminectomy sites may be an alternative method of minimizing postoperative epidural scar formation. PMID- 8446771 TI - The role of pancreatic innervation and cholecystokinin in the intestinal phase of pancreatic polypeptide release in conscious dogs. AB - Besides vagal cholinergic mechanisms, pancreatic polypeptide (PP) secretion is thought to be mediated by hormones. This study was performed to delineate the role of extrinsic pancreatic innervation and cholecystokinin (CCK) in amino acid- and fat-stimulated PP secretion. In ten mongrel dogs, pancreatic denervation was performed by the method of Debas et al. [3]. Total denervation of the pancreas did not alter PP response to intraduodenal application of amino acids (integrated output 24,434 +/- 3260 pmol/1 x 120 min before vs 22,797 +/- 2470 pmol/1 x 120 min after operation) and to intraduodenal fat solution (19,595 +/- 2121 pmol/1 x 120 min vs 19,983 +/- 2031 pmol/1 x 120 min). Also, no significant differences were measured in CCK release (491 +/- 71 pmol/1 x 120 min vs 430 +/- 57 pmol/1 x 120 min for amino acids, 571 = 63 pmol/1 x 120 min vs 563 +/- 89 pmol/1 x 120 min for fat solution). Plasma PP and CCK levels were compared by linear regression analysis. Correlations between PP and CCK were high in the intact pancreas (amino acids, r = 0.92; fat, r = 0.99) as well as in the denervated pancreas (r = 0.93 amino acids and r = 0.98 fat). These results show that extrinsic pancreatic innervation does not influence PP and CCK release after intraduodenal amino acids or fat solution and that PP secretion seems to be mediated to some extent through the release of CCK. PMID- 8446772 TI - PCR analysis of HIV1 infection of macrophages: virus entry is CD4-dependent. AB - Amplification of early reverse transcripts by the polymerase chain reaction has been used to measure HIV1 entry into H9 cells and primary macrophages. With a single-step method of DNA preparation, we performed time course experiments to follow the appearance of long terminal repeat DNA. In both cell types, the formation of DNA was completely inhibited by anti-CD4 antibody, confirming the requirement of CD4 for virus binding and entry, and demonstrating that there were no CD4-independent routes of infection. In agreement with previous infectivity studies, sCD4 inhibited the entry of IIIB into H9, but only partially blocked Ba L into macrophage when used at a comparable dose. PMID- 8446773 TI - Characterization of HIV1-PAR, a macrophage-tropic strain: cell tropism, virus/cell entry and nucleotide sequence of the envelope glycoprotein. AB - The HIV1-PAR strain, isolated from the cerebrospinal fluid of an HIV1 seropositive man suffering from encephalopathy, replicated well in cord blood lymphocytes, poorly in peripheral blood mononuclear cells, and to different levels in blood-derived macrophage (BDM) cultures prepared from different blood donors. In marked contrast to its replication in primocultures, it did not grow in CEM and U937 cell lines. HIV1-PAR production in BDM was inhibited by more than 90% after treatment with OKT4A or 13B8.2 monoclonal antibodies (mAb) binding to adjacent epitopes of the D1 domain of the CD4 molecules. A lower but significant inhibitory effect was observed after BDM treatment with BL4 and OKT4 mAb, directed to the D2 and D3 domain of the CD4 molecule, respectively. The entire HIV1-PAR envelope glycoprotein gene was amplified by polymerase chain reaction and sequenced. The deduced amino acid sequence of HIV1-PAR gp160 revealed the presence of 847 amino acids and 86% homology with the HIV1 LAV virus prototype. An alignment of the amino acid sequence of the envelope glycoprotein of HIV1-PAR and HIV1-LAV showed that the differences were mostly clustered within the five variable regions. Five CD4-binding domains, the gp120/gp41 cleavage site, the putative gp41 fusion domain and 21 out of the 22 cysteine residues were conserved in both isolates. The results further confirm the macrophage-tropic character of the HIV1-PAR virus. PMID- 8446774 TI - Expression of the Tat protein of HIV1 in human promonocytic U937 cells. AB - Numerous studies have shown that, upon HIV1 infection, human promonocytic U937 cells were induced to differentiate, as indicated, for example, by increased expression of adhesion molecules. One of the viral proteins involved in this process might be the Tat protein. Indeed, this viral protein, which is essential for productive infection, has also been shown to display growth-stimulating properties and immunomodulatory activities. In order to apprehend the role of the HIV1 tat gene in inducing the differentiation of HIV1-infected U937 cells, we have successfully introduced this gene into U937 cells by infecting them with retroviral particles transducing tat. The effect of the Tat protein constitutively expressed by these cells upon their differentiation was then evaluated by looking for the expression of the c-fos and of the c-fms proto oncogenes which are linked to the differentiation of myelomonoblastic cells. Northern blot analysis revealed in these cells, an increase in the transcription of these two proto-oncogenes, and this increase was amplified after treatment with phorbol myristate acetate. No such increase was observed in control U937 cells. These results indicate that, among HIV1 gene products, the Tat protein appears to trigger monocytic differentiation, and suggests that this viral protein directs progenitors of the monocyte/macrophage lineage towards a differentiation stage in which production of viral antigens and virions might be more efficient. PMID- 8446775 TI - Expression of macrophage products after in vitro infection of human monocytes/macrophages with HIV. AB - We studied the response of monocytes/macrophages (MO/MAC) to lipopolysaccharide (LPS) and interferon-gamma (IFN gamma) stimulation with respect to the expression of macrophage-specific products, i.e. macrophage-colony-stimulating factor (M CSF), c-fms, c-sis, tissue factors, transforming growth factor-beta (TGF beta) and interleukin-8 (IL8) after in vitro infection with HIV. The expression of IL8 was strongly elevated in HIV-infected cells, peaking at 4 h after stimulation with LPS. At that time, the uninfected control showed only weak expression of IL8. Other products, e.g. tissue factor, c-fms, M-CSF and TGF beta were not modulated after stimulation. In contrast to IL8, the expression of c-cis was significantly lower in infected cells after stimulation with IFN gamma compared to uninfected control cells. PMID- 8446776 TI - Target cells during early SIV encephalopathy. AB - Early encephalopathy was studied in rhesus macaques in the first month following intravenous (i.v.) infection with SIV-mac-251. Histopathological analysis of brain tissues showed slight gliosis, associated with perivascular infiltrates and occasional glial nodules. Immunophenotyping of brain tissue showed microgliosis with expression of MHC class II molecule and macrophage infiltration associated with a few lymphocytes. At the early stage of infection, most infected cells were perivascular, suggesting that infiltrating cells are the main route of entry of the virus into the brain. Using combined immunochemistry and in situ hybridization, it was shown that these infected perivascular cells were mostly macrophages. Later, SIV infected a limited number of cells expressing the same CD68 monocyte/macrophage/microglia marker. Using different genome probes, hypotheses concerning SIV RNA expression during early brain infection were tested. It was shown that the latent brain infection was not due to a complete transcription block, but rather to productive replication of SIV at a low level in a small number of target cells in the brain. Injection of SIV by the intracerebral (i.c.) route induced the same slight encephalitis as observed in i.v. inoculated animals. The very small number of infected cells found around the site of i.c. inoculation suggests that resident microglia are poorly susceptible to infection by SIV. PMID- 8446777 TI - Adhesion proteins on human microglial cells and modulation of their expression by IL1 alpha and TNF alpha. AB - Expression of adhesion proteins on human microglial cells was studied by immunocytochemistry. Both microglial cells and peripheral blood monocytes expressed beta 2 integrins and molecules of the immunoglobulin superfamily at similar levels whereas the expression of the beta 1 integrins (alpha 2-VLA (very late antigen), alpha 4-VLA, alpha 5-VLA, alpha 6-VLA) was higher on microglial cells than on monocytes. Stimulation of microglial cells with interleukin-1 alpha and tumour necrosis factor-alpha, the main cytokines detected in HIV1-infected central nervous system (CNS), increased the microglial expression of alpha 1-VLA, intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and beta 2 LFA-1 (leukocyte-function-associated molecule-1) but not of alpha L-LFA-1. Such an induction of adhesion molecules could facilitate penetration of HIV1-infected monocytes into brain parenchyma and their adhesion to CNS cells, and could maintain a chronic inflammation during human immunodeficiency virus-1 (HIV1) encephalopathy. PMID- 8446778 TI - In vitro infection of epidermal Langerhans cells with human immunodeficiency virus type 1 (HTLV-IIIB isolate). AB - Human epidermal Langerhans cells (LC) isolated from normal skin were infected in vitro with human immunodeficiency virus type 1 (HIV1). To control the permissivity of LC for HIV1, cells isolated from the epidermal sheet of normal skin by trypsinization were cocultured with HIV1-carrying promonocytic cells (U937) and observed by electron microscopy. An early sign of infection occurring in the coculture was the formation of retroviral type buds from LC membrane. Different steps in the process of viral budding up to virus release into the extracellular space were observed by electron microscopy. Treatment with either coupled phorbol esters/bacterial lipopolysaccharide or a recombinant cytokine (tumour necrosis factor alpha) did not significantly enhance viral production. The ability of in vitro infected LC to transmit virus to other haematopoietic cells and the consequences of such an infection on antigen-presenting function of LC remain to be elucidated. PMID- 8446779 TI - Distribution and infection of Langerhans cells in the skin of HIV-infected healthy subjects and AIDS patients. AB - The in situ content of cells of the reticuloendothelial system and lymphatic cells was examined in the skin of eight symptom-free HIV-positive individuals, three AIDS patients and eleven healthy immunocompetent volunteers. The epidermis was obtained in vivo by the suction blister technique. The numbers of CD68+, CD3+, CD8+, CD25-(IL2R)+ and HLA-DR+ intraepidermal cells proved to be independent of the number of CD4+ peripheral blood lymphocytes. At the same time, the intraepidermal concentrations of these cells were generally low in symptom free HIV-infected individuals. The strong inverse correlation between the number of epidermal Langerhans cells (LC) and the severity of immunodeficiency was quantitatively confirmed; an increase in LC in symptom-free HIV-infected individuals was found. Thus, the reduction in these cells which was observed in the epidermis of AIDS patients began at a significantly elevated level. In contrast to results from other studies, in AIDS patients, in the present study, the concentration of epidermal LC did not differ significantly from that of healthy immunocompetent volunteers. The immunohistochemical technique can be as effective as in situ hybridization for the detection of HIV in the skin. Our results suggest that the viral load of the skin is rather low in HIV-infected subjects. HIV was demonstrated in one cell of one AIDS case by in situ techniques and this result was confirmed by a polymerase chain reaction examination using the same amount of tissue as for the in situ techniques.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446780 TI - Decreased haematopoietic colony growth in long-term bone marrow cultures of HIV positive patients. AB - Deficiencies in bone marrow stromal cells, i.e. fibroblasts, macrophages, endothelial cells and adipocytes, are considered to play a pathophysiological role in HIV-associated haematopoietic failure. Long-term bone marrow cultures (LTBMC) enable the longitudinal investigation of haematopoietic progenitor cell and bone marrow stromal growth. Therefore, in this study, the haematopoietic colony growth of bone marrow from patients with severe HIV infection was compared to that from healthy controls in LTBMC. The total cumulated number of colony forming units/granulocyte-macrophage (CFU-GM) was 6.7-fold higher (293.6% vs. 44.0%, p < 0.01), that of colony-forming units/granulocyte-erythrocyte-macrophage megakaryocyte (CFU-GEMM) was 3.5-fold higher (28.7% vs 8.3%), and that of burst forming units/erythrocyte (BFU-E) was 31.1-fold higher (68.4% vs 2.2%) than that from HIV-positive patients, respectively (colony number before LTBMC = 100%). In contrast, the cumulated cell number at the end of LTBMC from HIV-positive patients was not reduced (cell numbers in percent of initially seeded cells: HIV positive 418.4%, HIV-negative 397.1%). The significantly reduced colony-forming capacity over a significantly shorter time span, without reduction in the absolute cell number, in LTBMC from patients with severe HIV-infection as compared to healthy controls, suggests that uncoupling between cell proliferation and differentiation is a pathophysiological mechanism in HIV-dependent haematopoietic failure. PMID- 8446781 TI - Modulation of HIV transcription in and release from human monocytic cells following phagocytosis of Mycobacterium tuberculosis. AB - The consequence of phagocytosis of Mycobacterium tuberculosis by human monocytic cells on transcription and release of human immunodeficiency virus (HIV) is unknown. In order to investigate the effects of phagocytosis of M. tuberculosis on HIV transcription, human monocytic THP-1 cells were transfected with constructs of the long terminal repeat of HIV1 or 2 linked to the chloramphenicol acetyl transferase gene (HIV LTR CAT). Following phagocytosis of M. tuberculosis by THP-1 cells maintained in non-adherent conditions, there was enhanced transcription of HIV LTR CAT. This enhancement was further potentiated when such THP-1 cells adhered to tissue culture plastic. Phagocytosis of M. tuberculosis by HIV-infected THP-1 cells in non-adherent conditions had no effect on intact HIV release. However in adherent conditions, phagocytosis of M. tuberculosis reduced release of intact virus even in the face of enhanced HIV transcription. Phagocytosis of M. tuberculosis by THP-1 cells affects HIV replication at both the transcriptional level (upregulates) and the level of viral release (down regulates) and is modified by cellular adhesion. PMID- 8446782 TI - Infection of dendritic cells with HIV1: virus load regulates stimulation and suppression of T-cell activity. AB - Patients with HIV infection show two major types of immunological effects. The first is hyperactivity of both T and B lymphocytes which may be in response to HIV antigens themselves, and the second is a loss in T-cell activity in response to other antigens. Dendritic cells (DC) show a higher rate of infection with HIV than other peripheral blood cells in vitro and in vivo. The effects of HIV infection of DC in vitro on their stimulating capacity for T cells were, therefore, examined. We compared the development of the capacity to stimulate primary proliferative responses to virus in autologous lymphocytes with their potency in stimulating allogeneic cells in the mixed leukocyte reaction (MLR). Small numbers of uninfected DC caused little or no stimulation of autologous lymphocytes, but stimulated high MLR. The level of HIV infection in in vitro infected DC preparations was dependent on the time of infection and the titre of the input virus. DC exposed to low doses of HIV (e.g., 10(3) TCID/10(6) cells) for up to 4 days or to a higher dose (e.g. 10(5) TCID/10(6) cells) for 1 day caused significant primary proliferation in autologous T cells and, under these conditions, capacity to stimulate allogeneic MLR remained intact. However, DC exposed to increasing doses of HIV or infected for a longer period showed reduced capacity to stimulate allogeneic lymphocytes and then a loss of stimulation of autologous cells. This provides evidence suggesting that both stimulatory and inhibitory effects of HIV infection can be produced through infection of DC. PMID- 8446783 TI - Accessory cells and macrophages in the histopathology of SIVsm-infected cynomolgus monkeys. AB - Thirty-three out of 39 cynomolgus monkeys (Macaca fascicularis) infected with SIVsm (strain SMM-3) developed various pathologies similar to those seen in human AIDS. Lymphadenopathy was frequently seen (72%) and was characterized by hyperplasia followed by involution of follicle/germinal centres due to follicular dendritic cell (FDC) destruction corresponding to the degree of immunodeficiency. Various organs such as the lungs, liver, central nervous system, kidneys, gastrointestinal tract, cardiovascular system and adrenals showed histopathological changes with prominent monocyte/macrophage and multinucleated giant cell formation. Eighteen (54%) monkeys presented with extranodal malignant lymphoma (ML) associated with marked CD4 decrease and destruction of follicular architecture. The high frequency of ML, giant cell disease and lymph node changes seen in the present SIV model provides an attractive system to elucidate the role of FDC and monocytes/macrophages in the pathogenesis of these conditions in common with HIV infection and human AIDS. PMID- 8446784 TI - The thymic epithelial reticulum and interdigitating cells in SIV-induced thymus atrophy and its comparison with other forms of thymus involution. AB - Alterations in the thymus were investigated in the early course of SIV infection of rhesus monkeys and compared with age-related and acute accidental thymus atrophy. The SIV-induced pathology was characterized by shrinkage of the thymic parenchyma and capsule, whereas in age-related thymus atrophy, the size of the capsule remained unaltered and the emerging space was filled by fatty tissue. Acute accidental thymus involution is characterized by massive cell death of the thymocytes, but there was no increase in pycnotic thymocytes either in SIV induced or in age-related thymus atrophy. Ultrastructural analysis revealed no major differences between the juvenile control and the aged thymus. In contrast, SIV-induced thymus atrophy exhibited severe alterations of the epithelial cells of the cortex and the interdigitating dendritic cells, which were not found in the aged thymus nor in the juvenile control cortex. PMID- 8446786 TI - Ethics in cardiopulmonary resuscitation. AB - There is a minority of patients in whom resuscitation is inappropriate. It is important to identify such patients beforehand and communicate the decision not to attempt resuscitation to the would-be first responders. In the absence of the patient's expressed wishes, any decision not to attempt resuscitation must be made by the senior doctor in charge. This doctor will take into account a number of factors and, when appropriate, consult with medical and nursing colleagues relatives, etc. before making such a decision. There are many factors influencing the decision to terminate resuscitation once it has been started. These are listed and discussed. Legal aspects are addressed and indications are made of the expected performance of lay and professional rescuers working under a variety of circumstances. The various definitions of death are described in the light of modern medical practice and the possibility of organ transplantation. There is an increasing fear of infection hazards to the rescuer during mouth to mouth ventilation. The risks are discussed and the use of protective devices is encouraged if they are immediately available. Finally, guidelines for hospital ethical CPR policy are outlined in the hope that they will be considered for adoption on a national and international scale. PMID- 8446785 TI - Human endothelial cells isolated from the hepatic sinusoids and the umbilical vein display a different permissiveness for HIV1. AB - Endothelial cells are now considered as potential targets for HIV infection, together with other non-lymphoid cells. We previously demonstrated that endothelial cells isolated from the human liver sinusoids (SEC) are permissive for HIV1 in vitro (Steffan et al., 1992), whereas human umbilical vein endothelial cells (HUVEC) do not allow replication of seven HIV1 and HIV2 strains under the same infection conditions (Lafon et al., 1992). The aim of our work was to compare the permissiveness of SEC and HUVEC and to determine whether the lack of HIV replication in HUVEC, which do not possess CD4 receptors (Lafon et al., 1992), could be related to the absence of virus penetration. The bypass of the early events in the virus life cycle, including the stage of fusion, by transfection of HUVEC with the HTLV-IIIB provirus led to one cycle of viral replication. Moreover, a low level of viral replication was observed in HUVEC infected with the NDK HIV strain, known to penetrate its target cell in a CD4 independent fashion. These results indicate that the block of infection in HUVEC takes place during the early stages of the viral replicative cycle. However, given the low level of NDK replication in HUVEC (0.02% infected cells) in comparison with NDK-infected SEC (30 to 50% infected cells), the absence of the CD4 receptor on HUVEC may not be the only limiting factor for viral growth. Although these two types of endothelial cells display a very different permissiveness for HIV, the present data suggest that they could both serve as a viral reservoir. PMID- 8446787 TI - Extracorporeal life support for patients undergoing prolonged external cardiac massage. AB - From November 1987 to February 1992, extracorporeal life support (ECLS) was used for four patients undergoing prolonged external cardiac massage following cardiac arrest. Their underlying diseases consisted of acute pulmonary embolism, pulmonary arterial thrombosis due to protein C deficiency, acute inferior left ventricular infarction accompanied by right ventricular infarction and thoracic contusion. After the initiation of ECLS, hemodynamic variables and metabolic acidosis improved in all of the cases. The case of pulmonary embolism and the case of acute myocardial infarction were successfully weaned from ECLS without complications. They were later discharged ambulatory from the hospital. The patient with pulmonary arterial thrombosis, who was comatose, became alert after the initiation of ECLS. However the patient finally died due to diffuse and massive pulmonary arterial thrombosis, which was probably related to protein C deficiency. The patient with thoracic contusion was also comatose before ECLS. He did not recover from the coma and died soon after the disconnection of ECLS. The latter two cases were suspected to have had irreversible organ failures not responsive to mechanical support of both circulation and respiration. We conclude that ECLS is a very useful method for patients requiring prolonged cardiac massage following cardiac arrest. PMID- 8446789 TI - Are we wasting talent and resources? PMID- 8446788 TI - Failure of nimodipine to prevent brain damage in a global brain ischemia model in the rat. AB - In view of our negative results with the calcium antagonist nimodipine as a cerebroprotective agent in a cardiopulmonary resuscitation model in the rat, we examined the protective effects of nimodipine in the four-vessel (carotid and vertebral) occlusion model, a model of global brain ischemia without important cardiovascular depression. Survival and neurological status were monitored and after 72 h the hippocampus was resected and examined for histological evaluation. The animals were treated blindly and randomly with either nimodipine, its solvent or saline given subcutaneously. In two separate studies, high doses (total dose: 5 mg/kg) or low doses of nimodipine (total dose: 1.6 mg/kg) were administered. In the high dose series, the survival rates at 72 h in the nimodipine group, the saline group and the solvent group were 4% (2/44), 19% (7/37) and 20% (8/41), respectively; in the low dose series, the figures were 26% (13/50), 34% (15/44) and 39% (18/46), respectively. The differences between nimodipine, solvent and saline were not statistically significant. Likewise, no differences in neurological status or histological brain damage were found. These data suggest that nimodipine offers no cerebral protection in global brain ischemia and may even be toxic, especially when given in high doses. PMID- 8446790 TI - Cardiovascular function and neurologic outcome after cardiac arrest in dogs. The cardiovascular post-resuscitation syndrome. AB - We studied cardiovascular changes and neurologic outcome at 72 h in 42 healthy dogs after normothermic ventricular fibrillation cardiac arrest (no blood flow) of 7.5, 10, or 12.5 min duration, reversed by standard external cardiopulmonary resuscitation (CPR) (< or = 10 min) and followed by controlled ventilation to 20 h and intensive care to 72 h. We found no difference in resuscitability, mortality, neurologic deficit scores, or overall performance categories between the three insult groups. There was no major pulmonary dysfunction. During controlled normotension post-CPR, all dogs presented a transient reduction in cardiac output. In the 12.5-min cardiac arrest group the decrease in cardiac output persisted beyond 12 h post-CPR (P < 0.01) and was associated with more severe arrhythmias (P < 0.05) and worse morphologic myocardial damage (P < 0.01). Both cardiac and neurologic malfunction at 72 h correlated with arrest time. Only cardiac malfunction correlated with CPR time. Neurologic recovery correlated with mild (inadvertent) pre-arrest hypothermia, diastolic arterial pressure during CPR and absence of cardiovascular impairment at 12 h post-CPR. We conclude that prolonged cardiac arrest in previously healthy dogs is followed by persistent cardiovascular derangements that correlate with impaired neurologic recovery. PMID- 8446791 TI - Assessment, development, and evaluation of cancer programs. PMID- 8446792 TI - Key roles and issues of the multidisciplinary team. PMID- 8446793 TI - Historical development of cancer programs. PMID- 8446794 TI - Quality management issues. PMID- 8446795 TI - Clinical trials and research in the community. PMID- 8446796 TI - Establishing a partnership: community involvement and the cancer program. PMID- 8446797 TI - The challenge of cancer care marketing. PMID- 8446798 TI - What cancer program managers must know: the fiscal and regulatory challenge. PMID- 8446799 TI - Organizational approaches to cancer program development. PMID- 8446800 TI - A new sequential procedure for surveillance of Down's syndrome. AB - A new method is proposed for the surveillance of Down's syndrome among newborn. Despite the strong dependence of overall risk of Down's syndrome on maternal age, it has been suggested that an environmentally induced increase in risk may be additive over all maternal ages. The surveillance method introduced here is specifically designed to detect such changes. The method is based on registry data for successive periods for a given population. It is assumed that the number of Down's syndrome cases as well as the total number of births are known in all maternal age groups. Tables of average run lengths until an alarm (ARLs) are calculated for a total sample size of 14,500 in each period, the approximate number of births in a three-month period in Norway. Comparison with the Poisson cusum shows that the new surveillance method can detect moderate additive increases significantly faster. Applied retrospectively to quarterly data from the Medical Birth Registry of Norway for 1978-89, the proposed method was close to an alarm in 1985 and actually signalled a strong alarm in 1986, reflecting a previously reported increase in risk in this period. The cusum method was not so sensitive to the aberration in Down's syndrome risks in 1985 and 1986. PMID- 8446801 TI - A refinement to the analysis of serial data using summary measures. AB - A widely used method for the analysis of data collected serially over time is to reduce the data on each subject to a single summary that reflects some salient aspect of the response. The summaries from all subjects are then analysed using appropriate univariate methods. In some cases it may be unreasonable to suppose that summaries in a group share a common distribution. A weighted analysis may be preferable, with data from each subject used to determine the weights. This approach is explored in the context of an analysis of data on foetal distress during labour. PMID- 8446802 TI - Direct standardization of incidence rates in the presence of incomplete data. AB - When comparing the disease incidence rates for several subpopulations, epidemiologists often use direct standardization to adjust for potential confounding variables. In population-based studies, however, the data are often incompletely classified with respect to membership in the subpopulations of interest. In such a situation, one often assumes that the cases with missing data have the same distribution as the complete cases, that is the data are missing completely at random. In this setting, we derive variance estimates for the directly standardized rates which account for the use of incomplete data. We illustrate the use of these methods with data from a study of the incidence of gastrointestinal cancer by immigrant status where birthplace data are often incomplete. PMID- 8446803 TI - Establishing a national in vitro fertilization registry: methodological problems and analysis of success rates. AB - A national registry for in vitro fertilization (IVF) was established in France in January 1986 and has been in operation since that date. During 1987, data on 14,763 attempts were collected from 72 teams, representing 80 per cent of all French IVF activity. In this registry, a form is completed for every oocyte recovery attempt, containing information about the infertility diagnosis, the attempt itself and its result. This paper presents results for the years 1986 and 1987 and studies the relationship between pregnancy occurrence and some couple or cycle characteristics. Methodological aspects are discussed, concerning the possible sources of bias, and the analysis of results. Results obtained in this registry are compared with those from other similar registries. PMID- 8446804 TI - The succession procedure for interim analysis: extensions for early acceptance of Ho and for flexible times of analysis. AB - The succession procedure is a new method for group sequential analysis based on a succession of significant tests. In this paper, the procedure is extended by the addition of a lower boundary, which allows the early acceptance of the null hypothesis Ho according to the stochastic curtailing approach. The succession procedure is also adapted to the type I error spending rate function alpha *(t), leading to the method of semisequential analysis for which the times of analysis need not be specified in advance. PMID- 8446805 TI - Analysis of crossover designs with multivariate response. AB - Crossover designs involve observing the same response variate under different experimental conditions for each subject. Univariate methods are commonly used for analysis of data arising in these designs, but multivariate procedures offer a more general approach. The general multivariate linear model provides a natural framework for the simplest data structure as well as more complex settings with two or more response variates and measurements repeated over time. Multivariate models for crossover designs provide a unified approach that clarifies specification of hypotheses, assumptions required, and testing procedures in a wide class of applications that include longitudinal data as a special case. We focus on the 2 x 2 crossover design, but also describe models for analysing more complex crossover designs. PMID- 8446806 TI - Covariate imbalance and conditional size: dependence on model-based adjustments. AB - Analysis of covariance (ANCOVA) is frequently recommended to correct for covariate imbalance and to control conditional size of hypothesis tests in randomized designs. Such control, however, depends on the accuracy of the ANCOVA model used to make the adjustments. Examination of residuals together with knowledge of the subject matter are important for obtaining an accurate model. Stratified assignment procedures lessen the dependence of proper control of conditional size on the specific model used in the adjustment procedure. PMID- 8446807 TI - A comprehensive algorithm for determining whether a run-in strategy will be a cost-effective design modification in a randomized clinical trial. AB - In randomized clinical trials, poor compliance and treatment intolerance lead to reduced between-group differences, increased sample size requirements, and increased cost. A run-in strategy is intended to reduce these problems. In this paper, we develop a comprehensive set of measures specifically sensitive to the effect of a run-in on cost and sample size requirements, both before and after randomization. Using these measures, we describe a step-by-step algorithm through which one can estimate the cost-effectiveness of a potential run-in. Because the cost-effectiveness of a run-in is partly mediated by its effect on sample size, we begin by discussing the likely impact of a planned run-in on the required number of randomized, eligible, and screened subjects. Run-in strategies are most likely to be cost-effective when: (1) per patient costs during the post randomization as compared to the screening period are high; (2) poor compliance is associated with a substantial reduction in response to treatment; (3) the number of screened patients needed to identify a single eligible patient is small; (4) the run-in is inexpensive; (5) for most patients, the run-in compliance status is maintained following randomization and, most importantly, (6) many subjects excluded by the run-in are treatment intolerant or non compliant to the extent that we expect little or no treatment response. Our analysis suggests that conditions for the cost-effectiveness of run-in strategies are stringent. In particular, if the only purpose of a run-in is to exclude ordinary partial compliers, the run-in will frequently add to the cost of the trial. Often, the cost-effectiveness of a run-in requires that one can identify and exclude a substantial number of treatment intolerant or otherwise unresponsive subjects. PMID- 8446808 TI - Harmonic regression analysis of the effect of drug treatment on the diurnal rhythm of blood pressure and angina. AB - Harmonic regression is a method for analysis of diurnal rhythms which we apply to blood pressure and angina attack rate. We show that population amplitude and phase as previously defined are not the expected values of amplitude and phase in the population unless patients are in phase and that the estimates of these population parameters are the amplitude and phase of the mean measurements of the observation times. We show that the amplitude of the mean measurements underestimates the magnitude of the diurnal rhythm of individual patients due to significant differences among patients in the phase parameter. Thus, the mean of the individual-patient amplitudes and phases, rather than the amplitude and phase of the mean measurements, is necessary to describe the diurnal rhythm in the population and to assess the effect of drug treatment. Harmonic regression analysis yields specific hypotheses that relate directly to the consistency of drug effect over 24 hours. PMID- 8446809 TI - On the efficacy of the rank transformation in stepwise logistic and discriminant analysis. AB - We have evaluated the performance of four stepwise variable selection procedures commonly used in medical and epidemiologic research. The four procedures are discriminant and logistic regression and their rank transformed versions, where the independent variables are replaced by their ranks. We generated, by computer, data for two groups from several distributions with a variety of sample sizes and covariance matrices. The two ranking procedures each increased the chance of correctly selecting those variables related to group membership for data generated from log-normal or contaminated distributions. For normally distributed data the ranking procedure had little effect on variable selection. Rank transformed discriminant analysis and rank transformed logistic regression were equally effective in selecting variables when sample sizes exceeded 100. Rank transformed discriminant analysis was superior for smaller data sets. We discuss the implications of the results of this study for clinical and epidemiologic research. PMID- 8446810 TI - A method to test for a recent increase in HIV-1 seroconversion incidence: results from the Multicenter AIDS Cohort Study (MACS). AB - We have formulated the problem of determining whether there has been an upturn in HIV-1 seroconversion incidence over the first five years of follow-up in the Multicenter AIDS Cohort Study (MACS) as that of locating the minimum of a quadratic regression or examination of two-knot piecewise spline models. Under a quadratic model, we propose a method to obtain a direct estimate and a bootstrap estimate for the location of the temporal turning point (local minimum) for HIV-1 seroconversion incidence and three methods to estimate confidence intervals for the location of the turning point for HIV seroconversion incidence: (1) Wald confidence interval estimate with or without log transformation assuming the asymptotic normality and applying the Delta method; (2) asymmetric confidence intervals using Fieller's Theorem and its modification; and (3) bootstrapping confidence intervals. Inferences for the temporal turning point based on Wald tests for a single regression term in a non-linear regression model were not reliable compared to inferences based on confidence intervals placed on calendar time. We present results using these different methods applied to the MACS data and we obtain power estimates to illustrate the performances of different methods. PMID- 8446811 TI - The design of observer agreement studies with binary assessments. AB - We discuss the design of observer agreement studies with binary assessments, with particular emphasis on the need for adequate sample size and the use of replicate observations. First, we present a method and tables for determining the sample size required for ensuring a desired precision for the estimate of the probability of disagreement between two observers. Second, for studies including replicate observations, we present a statistical model that allows estimation of the magnitude of within- and between-observer variation. We then derive sample sizes guaranteeing a specified precision for these estimates, present tables of these sample sizes and give examples of their use. PMID- 8446812 TI - A pocket-calculator algorithm for the Shapiro-Francia test for non-normality: an application to medicine. AB - An easy-to-calculate approximation to the Shapiro-Francia W' test and its P-value is proposed. Its accuracy is sufficient for practical application in samples of size 5 or larger. PMID- 8446813 TI - On tests for equality of predictive values for t diagnostic procedures. PMID- 8446814 TI - [Antiretroviral therapy]. PMID- 8446815 TI - [Clinical aspects and therapeutic approach in cutaneous lesions of lupus erythematosus]. PMID- 8446816 TI - [Diagnosis of non-palpable breast lesions: value of stereotaxically-guided needle biopsy]. PMID- 8446817 TI - [Interdisciplinary meeting on AIDS. Introduction]. PMID- 8446818 TI - [AIDS: epidemiology and diagnosis]. PMID- 8446819 TI - [Early manifestations of acquired immunodeficiency]. PMID- 8446820 TI - [Opportunistic infections in advanced immunodeficiency]. PMID- 8446821 TI - [Skin manifestations in human immunodeficiency virus infection]. PMID- 8446822 TI - Relationship between the lactate and ventilatory thresholds during prolonged exercise. AB - The anaerobic threshold is commonly measured by either blood lactate (lactate threshold) or ventilatory gases (ventilatory threshold); however, the relationship between these 2 methods is not conclusive. The lactate threshold has been characterised at either a fixed or variable blood lactate concentration (BLa). Recent studies have indicated a specific blood lactate concentration for each individual which considers the interindividual variations in lactate kinetics (individual anaerobic threshold), following either a continuous, exponential pattern or a discontinuous, threshold-like response. The ventilatory threshold is assessed using a variety of ventilatory parameters, many of which exhibit a threshold-like response during progressive exercise. Despite the apparent causal relationship between the stimulation of the ventilatory chemoreceptors and ultimately the ventilatory response and the accumulation of protons in the circulating blood, evidence does exist which refutes such a connection. Such evidence supporting a coincidental relationship examines no significant change in ventilation with significant increases in blood lactate concentration. Conversely, evidence from patients with McArdle's disease indicates that although no lactic acid is produced, these individuals do experience a threshold-like ventilatory response during incremental exercise. The ability to perform at the anaerobic threshold is now recognised as an integral component of endurance events. Several studies have concluded that the ventilatory threshold is highly correlated with endurance performance, in distances ranging from 26 miles (41.6 km) [r = -0.94] to 5 and 10 km (r = 0.945). The lactate threshold, in particular the individual anaerobic threshold, has been examined from a performance standpoint. Much of the literature supports the individual anaerobic threshold as the exercise intensity at which performance is maximal and able to be sustained for at least 50 minutes. With the variety of techniques utilised in assessing the anaerobic threshold, caution should be taken in interpretation of the results as the different protocols may elicit a variety of responses during incremental exercise. Furthermore, it is essential to account for the individual's unique response to such exercise. PMID- 8446823 TI - Selected scientific aspects of marathon racing. An update on fluid replacement, immune function, psychological factors and the gender difference. AB - Four topics are addressed: fluid/fuel replacement during the marathon, marathoning and susceptibility to infection, psychological aspects of elite marathoners and the gender gap in marathon performance. Although these topics are diverse, they all relate to practical questions raised by coaches and athletes. Evidence from laboratory and field studies indicates that it is advisable for marathoners to consume 800 to 1000 L/h of sports drink providing 45 to 60 g/h of carbohydrate. It is strongly suggested to practice fluid consumption during training sessions as it is probable that tolerance to drinking during running is a trainable adaptation. Epidemiological and clinical research support the concept that marathon training and racing increase the runner's risk of upper respiratory tract infections because of negative changes in immune function. Susceptibility to infection may be reduced by proper nutrition, adequate sleep, appropriate recovery between vigorous workouts and minimal exposure to sick people during periods of heavy training and major races. Although psychological research in this area is still limited, evidence suggests that elite marathoners rely primarily on associative strategies during competition while judiciously dissociating in order to cope with pain. It is recommended that coaches and athletes interested in employing psychological interventions seek assistance from professionals well trained in the fields of both psychology and exercise science. Will women soon outrun men? Over the past 2 decades societal views and training practices of women distance runners have changed greatly, yet certain performance related biological differences between men and women are unlikely to change. PMID- 8446824 TI - Shoulder arthroscopy in the athlete. Practical applications. AB - Shoulder arthroscopy may be a useful tool to the surgeon in confirming a diagnosis for therapeutic treatment of a diagnosed condition. Shoulder arthroscopy has provided valuable information in establishing a diagnosis in the athletic individual when overlapping symptoms make a clinical diagnosis difficult. Shoulder arthroscopy for shoulder instability is in its developmental stages with early studies showing a high redislocation rate. Impingement syndrome is initially treated with conservative methods; however, if this is unsuccessful acromioplasty can be considered. Arthroscopic acromioplasty allows a thorough examination of the glenohumeral joint. Patients with rotator cuff tears may get pain relief with arthroscopic debridement. Inflammatory diseases such as rheumatoid arthritis can be treated with arthroscopic synovectomy. Shoulder arthroscopy is a valuable tool in the treatment and diagnosis of shoulder disorders. PMID- 8446825 TI - Alcohol and sport. Impact of social drinking on recreational and competitive sports performance. PMID- 8446826 TI - The effects of early mobilisation and immobilisation on the healing process following muscle injuries. AB - The biological processes following muscle injury include 2 competitive events; regeneration of muscle fibres and the simultaneous production of granulation tissue. We have studied the effects of early mobilisation and immobilisation on the healing of rat gastrocnemius muscle following partial rupture by a controlled contusion mechanism. Muscle fibre regeneration is inhibited by the formation of dense connective tissue scar. Immobilisation following injury limits the size of the connective tissue area formed within the site of injury; the penetration of muscle fibres through the connective tissue is prominent but their orientation is complex and not parallel with the uninjured muscle fibres. Immobilisation for longer than 1 week is followed by marked atrophy of the injured gastrocnemius muscle. Mobilisation started immediately after injury is followed by a dense scar formation in the injury area prohibiting muscle regeneration. When mobilisation is started after a short period of immobilisation a better penetration of muscle fibre through the connective tissue is found and the orientation of regenerated muscle fibres is aligned with the uninjured muscle fibres. Although a little delay in healing processes in muscles mobilised after short immobilisation was found morphologically, the gain in strength and energy absorption capacity was quite similar and as good as that of muscles treated by early mobilisation alone. PMID- 8446828 TI - Repeated partial sleep deprivation progressively changes in EEG during sleep and wakefulness. AB - The effect of repeated partial sleep deprivation on sleep stages and electroencephalogram (EEG) power spectra during sleep and wakefulness was investigated in nine healthy young subjects. Three baseline nights of 8 hours (2300-0700 hours) were followed by four nights with 4 hours of sleep (2300-0300 hours) and three recovery nights of 8 hours (2300-0700 hours). Sleep restriction curtailed sleep stages 1 and 2 as well as rapid eye movement (REM) sleep, but left slow wave sleep largely unaffected. In the first two recovery nights, total sleep time and REM sleep were enhanced, and sleep latency was shortened. Slow wave sleep was increased only in the first recovery night. In accordance with the prediction of the two-process model of sleep regulation, slow wave activity (SWA; spectral power density in the 0.75-4.5-Hz range) in nonrapid eye movement (NREM) sleep increased by approximately 20% in the first night following sleep restriction, remained at this level in the subsequent 3 nights and decreased immediately after the first recovery night. In contrast to these immediate changes, progressive and more persistent changes were seen in the EEG activity of higher frequencies. Thus, activity in the upper delta band tended to gradually increase from night to night during the sleep restriction period, whereas after an initial increase, activity in the theta-alpha band changed in the opposite direction. The progressive changes were also present in the EEG spectra of REM sleep and wakefulness. Because the time course of these changes paralleled the cumulative deficit in REM sleep, they may represent a correlate of REM sleep pressure. PMID- 8446827 TI - Commercially marketed supplements for bodybuilding athletes. AB - We conducted a survey of 624 commercially available supplements targeted towards bodybuilding athletes. Over 800 performance claims were made for these supplements. Supplements include amino acids, boron, carnitine, choline, chromium, dibencozide, ferulic acid, gamma oryzanol, medium chain triglycerides, weight gain powders, Smilax compounds and yohimbine. Many performance claims advertised were not supported by published research studies. In some instances, we found no research to validate the claims; in other cases, research findings were extrapolated to inappropriate applications. For example, biological functions of some non-essential compounds were interpreted as performance claims for the supplements. Claims for others were based on their ability to enhance hormonal release or activity. We suggest that more research be conducted on this group of athletes and their nutritional needs. Furthermore, the effectiveness and safety of supplements merit further investigation. PMID- 8446829 TI - Multiple sleep latency test (MSLT) and sleep apnea in aged women. AB - Sleep disturbance and the tendency to sleep during the day were assessed polysomnographically in 31 elderly women (mean age = 76.7 +/- 3.6 SD) recruited from a senior citizen's living facility without reference to sleep-wake complaints. The data showed that the level of sleepiness during the day in each subject depended in part on the severity of her respiratory disturbance. It was found that the group (n = 7) of elderly females with apnea and hypopnea index (AHI) higher than 20 was more sleepy [multiple sleep latency test (MSLT) = 7.9 +/ 2) than the group (n = 10) with AHI > 5 but less than 20 (MSLT = 12.7 +/- 5). Nevertheless, the presence and severity of respiratory disturbance were not the only factors that influenced the level of sleepiness during the day in the studied sample. A subgroup of four elderly females showed a marked sleepiness during the four tested periods (MSLT = 5.2 +/- 0.6) with a very low respiratory disturbance index (AHI = 5.5 +/- 0.8). PMID- 8446830 TI - Predictive value of clinical features in diagnosing obstructive sleep apnea. AB - We examined the predictive value of history and physical examination in the diagnosis of obstructive sleep apnea (OSA) syndrome. This was achieved by studying a set of 594 patients referred to the sleep clinic because of suspicion of sleep apnea. All patients were asked a set of standard sleep-related questions and all had nocturnal polysomnography. We used stepwise multiple linear regression analysis to examine the relationship between the apnea/hypopnea index (AHI), defined as the number of episodes of cessation of breathing per hour of sleep (dependent variable), and age, sex, body mass index (BMI) and replies to the sleep questionnaire (independent variables). We found that age, sex, body mass index, bed partner observation of apnea and pharyngeal examination were significant predictors of AHI, explaining 36% of the variability. Subjective impression of the examining clinician was also an independent significant predictor of AHI, accounting for 10% of the variability. Using a conventional cutoff value of 10 to divide patients into apneics (AHI > 10) and nonapneics (AHI < or = 10), the sensitivity of subjective impression was 60% and the specificity 63%. We conclude that although clinical features obtained during history and physical examination explain a relatively high percent of the variability in AHI, subjective clinical impression alone is not sufficient to reliably identify patients with or without sleep apnea. PMID- 8446831 TI - Evidence of a perceptual-encoding deficit in narcolepsy? AB - Body temperature, vigilance, memory, information processing and motor function were examined in 10 unmedicated narcoleptics and 10 matched controls at four different times of day. Time of day and body temperature were not related to performance. Narcoleptics displayed selective cognitive deficits in response latency, word recall, and estimation of frequency. Narcoleptics did not differ from controls in motor speed, vigilance, information processing speed or decision making accuracy. We propose that a perceptual-encoding deficit may underlie the problems in memory and complex reaction time associated with narcolepsy. PMID- 8446832 TI - Attention, stress and negative emotion in persistent sleep-onset and sleep maintenance insomnia. AB - This study investigated the relation of negative emotions, attention and stress to sleep parameters in insomniacs. It also assessed whether sleep-onset insomniacs differ from sleep-maintenance/mixed insomniacs in the relations of these variables to sleep parameters. Fourteen sleep-onset insomniacs, 13 sleep maintenance or mixed insomniacs and 13 normal sleepers were recruited using two sequential questionnaires. The groups differed significantly on diagnostically relevant sleep parameters, assessed over 1 week by sleep diary. After completing standard anxiety, anger and depression inventories, subjects participated in two laboratory procedures during which electrophysiological responses were recorded: orienting response habituation and emotional stress elicitation. The 28 significant correlations of sleep parameters with emotion, habituation and stress measures averaged r = 0.415. In multiple regression analyses, emotion, attention and stress variables accounted for an average of 41% of the variance in sleep parameters (mean R = 0.64). Discriminant function analysis using these variables correctly classified 66% of the subjects into the three groups. It was concluded that negative emotions, stress responsiveness and attentional factors interact to influence insomnia. PMID- 8446833 TI - Spectral power and coherence analysis of sleep EEG in AIDS patients: decrease in interhemispheric coherence. AB - Fifteen patients aged between 26 and 55 years with the acquired immunodeficiency syndrome (AIDS) and various cerebral manifestations of the disease underwent an all-night sleep electroencephalogram (EEG) registration. The recordings of 15 age matched volunteers were examined as controls. Sleep stages were determined visually and the following spectral analysis was based on corresponding artifact free 40-second periods. The sampling rate was 64 second-1, the spectral resolution was 0.25 Hz and the frequency ranged from 0.25-24 Hz. The power density spectra of eight EEG derivations (left and right frontopolar, frontal, central and occipital; reference montage to the ipsilateral Cb electrodes) and the coherence spectra of interhemispheric (interfrontal, interoccipital) and intrahemispheric (frontooccipital, left and right) channel pairs were computed. The power density of the patients in the 11.5-13-Hz frequency range of nonrapid eye movement (NREM) sleep was considerably lower than that of the controls (p < 0.05 and p < 0.01 at left and right frontal derivations, two-tailed Mann-Whitney U test). The power density of rapid eye movement (REM) sleep showed no consistent differences between the two groups. The interfrontal coherence of the whole frequency range below 12 Hz was markedly lower in the patient group. This applied to NREM sleep and also to REM sleep (p < 0.01 and p < 0.001 for different frequency bands between 1 and 12 Hz in NREM and REM sleep). Possible relations to clinical features are discussed. PMID- 8446834 TI - Ambulatory activity monitoring during sleep: an evaluation of internight and intrasubject variability in healthy persons aged 50-98 years. AB - The aim of this study was to assess the internight and intrasubject variability of nocturnal activity and immobility measures of 99 healthy subjects aged 50-98 years. Motor activity was recorded at home during 6 successive nights with a wrist-worn activity monitor. The occurrence of suprathreshold motor activity was recorded over 15-second epochs. For each subject, six mean measures reflecting activity or immobility during sleep and their coefficient of variation were calculated. Our results revealed no first-night effect or day-of-week effect of the activity and immobility measures over the 6 nights across all subjects. On the other hand, for all nocturnal activity and immobility measures, a considerable intrasubject variability across the 6 nights was found. Females had a greater intrasubject variability of the mean duration of immobility periods and the movement index than males. The intrasubject variability of all nocturnal activity and immobility measures across the successive age groups remains stable. These findings emphasize that although a first-night effect may be lacking, the intrasubject variability of activity and immobility measures across several nights may still be considerable. PMID- 8446835 TI - Use of the wrist actigraph to study insomnia in older adults. AB - Measures derived from the wrist actigraph have been found to correlate highly with EEG measures of normal sleep. Although the actigraph has been used to study normal sleep, few studies have used the actigraph as a measure of sleep of elderly insomniacs. The present study, which used elderly insomniacs, sought to investigate the sensitivity of the actigraph to detect the effects of an insomnia treatment. The actigraph was sufficiently sensitive to detect the effect of the sleep restriction therapy used on several sleep measures. Subsidiary analyses suggested that the sleep log, although not an accurate measure of sleep, may be useful as a measure of elderly insomniacs' subjective perception of sleep. Because the actigraph can be used more easily and less expensively than the polysomnogram, the actigraph appears to be a promising measure for assessing the efficacy of treatment interventions in elderly insomniacs. PMID- 8446836 TI - Are buckling force measurements reliable in nocturnal penile tumescence studies? AB - The study of nocturnal penile tumescence (NPT) is frequently used to evaluate male erectile dysfunction. Buckling force, a measure of rigidity, is an important part of this evaluation, but its reliability is unknown. Accordingly, we studied the reliability of buckling force measurement and the stability of "maximum buckling force" between consecutive NPT series repeated in the same subject. For individual subjects, we correlated buckling forces for separate episodes of sleep related tumescence that were of comparable fullness (0-100%) as rated by a technician's visual estimates. For healthy control subjects, test-retest correlations were > 0.8 both within-night and across study series separated by an average of 70 weeks. In depressed men, correlations within nights were > 0.9, but fell to 0.64 across study series separated by an average of 21 weeks. Despite the high reliability of buckling force measurement, we found little stability of "maximum buckling force" between NPT series for individual subjects. Considerable variability in the maximum degree of penile rigidity was seen over time despite a constant level of reported daytime erectile function. We conclude that although penile rigidity is one of the more important variables in the assessment of male erectile dysfunction and can be measured reliably, the instability of maximum rigidity during sleep-related erections suggests that it is, at best, an imprecise correlate of daytime erectile function. PMID- 8446837 TI - Bizarreness effect in dream recall. AB - This study aimed to ascertain a) whether morning reports of dream experience more frequently reproduce bizarre contents of night reports than nonbizarre ones and b) whether this effect depends on the rarity of bizarre contents in the dream or on their richer encoding in memory. Ten subjects were awakened in rapid eye movement (REM) sleep three times per night for 4 nonconsecutive nights and asked to report their previous dream experiences. In the morning they were asked to re report those dreams. Two separate pairs of judges scored the reports: the former identified the parts in each report with bizarre events, characters or feelings and the latter parsed each report into content units using transformational grammar criteria. By combining the data of the two analyses, content units were classified as bizarre or nonbizarre and, according to whether present in both the night and corresponding morning reports, as semantically equivalent or nonequivalent. The proportion of bizarre contents common to night and morning reports was about twice that of nonbizarre contents and was positively correlated to the quantity of bizarre contents present in the night report. These findings support the view that bizarreness enhances recall of dream contents and that this memory advantage is determined by a richer encoding at the moment of dream generation. Such a view would seem to explain why dreams in everyday life, which are typically remembered after a rather long interval, appear more markedly bizarre than those recalled in the sleep laboratory. PMID- 8446838 TI - The ischiocavernosus and bulbospongiosus muscles in mammalian penile rigidity. AB - The role of the perineal muscles in erection physiology is currently controversial. Specifically, confusion persists as to the function, if any, the ischiocavernosus (IC) and bulbospongiosus (BS) muscles possess in nonejaculatory erections. An extensive review of the evidence for and against such an erectile role across five orders of mammalian species indicates that the IC muscles create rigidity by producing suprasystolic intracavernous pressures. The BS muscles, on the other hand, are primarily involved in expelling semen during ejaculation. Beckett and coworkers were the first to demonstrate a clear relationship between IC muscle contractions, suprasystolic intracavernous pressures and rigidity. This Beckett model is used to differentiate an erect phase from a rigid erect phase in the erection cycle. The involvement of these muscles in sleep-related erection physiology is also reviewed. Clinical implications and directions for future research are discussed. PMID- 8446840 TI - Bibliography of recent literature in sleep research. PMID- 8446839 TI - Absence of REM sleep, altered NREM sleep and supranuclear horizontal gaze palsy caused by a lesion of the pontine tegmentum. AB - A 27-year-old woman with a mass lesion confined to the pontine tegmentum had absence of rapid eye movement (REM) sleep and abnormal nonrapid eye movement (NREM) sleep with no sleep spindles when the sole neurologic manifestation was a bilateral supranuclear horizontal gaze palsy. This study suggests that the tegmentum nuclei associated with REM sleep generation in humans and the pathways that control horizontal eye movements are closely related. Furthermore, these findings indicate that bilateral damage of the pontine tegmentum is necessary for REM sleep abolition. Interruption of connections between the tegmentum of the pons and the reticular nuclei of the thalamus could be the cause of the absence of sleep spindles. PMID- 8446841 TI - The sleep-evoked decrease of body temperature. AB - The circadian rhythm of deep body temperature consists of both an endogenous component and evoked components resulting from exogenous influences. Previous studies of the sleep-evoked effect have failed to control confounding influences, so that the effect of sleep per se has not been established. In the present study, eight good sleepers had their rectal temperatures recorded for 24 hours in each of two laboratory conditions employing a constant routine to control exogenous influences. Sleep was allowed at night in one condition. Following sleep onset, body temperature dropped more rapidly and remained lower than when wakefulness continued over the same time, resulting in a mean sleep-evoked decrease of 0.31 +/- 0.09 degree C. Fourier regression analysis showed a significant 24-hour (circadian) temperature rhythm, together with a 12-hour harmonic rhythm, in each condition. Circadian rhythm parameters were also altered by the sleep-evoked (or masking) effect, with the amplitude increased and the mean decreased when subjects slept at night in the constant routine. It was suggested that a constant routine methodology be used in studies of circadian rhythm differences and that Fourier regression be used in preference to simple cosine curve fitting to give a better approximation of the temperature rhythm. PMID- 8446842 TI - Barrett's esophagus and esophageal adenocarcinoma. Endoscopic and histologic surveillance. PMID- 8446843 TI - The value of ultrasound in the follow-up of patients treated with biliary lithotripsy. Implications for monitoring patients after nonsurgical therapy of gallbladder stones. AB - To establish the value of ultrasound (US) in the follow-up of patients treated with extracorporeal shockwave lithotripsy (ESWL), the results of 484 US examinations of 87 patients were analyzed and related to the results of ESWL. Reliability of US in assessing efficacy was investigated by comparing consecutive US examinations. Unreliable US results were found in 36 patients (41%); in 7 patients US failed to demonstrate fragments. In nine patients (10%) unreliable US findings contributed to delayed retreatment with ESWL. To prevent errors in treatment regimen, verification of US findings is advised in case no fragments or fragments < 5 mm are found. In 22 patients (25%) US findings appeared indicative of hampered stone migration. Only 2 of these 22 patients (9.1%) became free of stones, compared with 32 of the remaining 65 patients (49.3%) (p < 0.01), even though both groups had similar initial stone characteristics and similar time of follow-up. US findings such as a contracted gallbladder or a common bile duct > 7 mm therefore indicate poor efficacy of ESWL. PMID- 8446844 TI - Ketotifen--old drug, new indication: reduction of gastric mucosal injury. AB - The objective of the present study was to determine the efficacy of ketotifen (Zaditen), an effective antiasthmatic drug, in preventing indomethacin-induced gastroduodenal mucosal injury in a two-arm prospective, randomized, double-blind, controlled and open study. Thirty healthy volunteers with endoscopic normal appearing mucosa were randomly treated, double-blindly, for 1 week with either placebo or ketotifen, 2 mg twice daily. On day 7 indomethacin, 50 mg three times daily, was added. Two subjects, one from each group, were withdrawn from the study owing to non-compliance. Ten additional subjects received ketotifen, 2 mg twice daily, 24 h before indomethacin administration, in an open manner. A second endoscopy was performed 24 h after indomethacin was initiated. Mucosal damage in the stomach and duodenum (hemorrhages, erosions, ulcers) was scored in accordance with Lanza et al. or counted numerically. Adverse reactions were documented. Ketotifen reduced indomethacin-induced gastric mucosal damage, reducing the mean gastric lesion score from 2.85 +/- 0.20 in the placebo-treated group to 1.86 +/- 0.36 and in the subjects pretreated with ketotifen for 7 days. Ketotifen protected (lesion score < or = 1) 6 of 14 subjects pretreated for 7 days, whereas none of the 14 placebo-treated subjects were protected. Ketotifen had no statistically significant protective effects in the duodenum. In the open study lesion scores of patients pretreated with ketotifen for 24 h were similar to those pretreated for 7 days. Ketotifen is effective in the reduction of indomethacin-induced acute gastric mucosal injury. Further studies are required to verify these data in a more relevant clinical setting. PMID- 8446845 TI - Specificities of monoclonal antibodies to domain I of alpha-gliadins. AB - Eight monoclonal antibodies were raised against a sequenced 54-amino-acid peptide of alpha-gliadin, which is thought to exacerbate coeliac disease. Five of the antibodies cross-reacted with coeliac non-toxic cereals. Two of eight of the antibodies bound specifically to coeliac toxic prolamins. These two antibodies cross-reacted with high molecular weight gliadins, which are closely related to alpha-gliadins and whose toxicity to patients with coeliac disease is unclear. The antibodies were screened by enzyme-linked immunosorbent assay against three amino-acid-sequenced peptides of alpha-gliadin with single amino-acid differences. Differential binding of antibody WC2 suggested that this antibody binds in the region of amino-acid residue 36, a proline residue, where there may be an antigenic beta-reverse turn. This proline residue forms part of a tetrapeptide motif, QQQP, which is thought to be present in all coeliac-active peptides. PMID- 8446846 TI - Lansoprazole versus omeprazole in short-term treatment of reflux oesophagitis. Results of a Scandinavian multicentre trial. AB - To evaluate the therapeutic potential of the newly developed proton pump inhibitor lansoprazole in patients with reflux oesophagitis, we performed a double-blind randomized clinical trial comparing 20 mg omeprazole and 30 mg lansoprazole, involving 229 patients at 9 Scandinavian hospitals. The treatment period was 4 or 8 weeks, and main efficacy variables were healing of endoscopic changes, relief of reflux symptoms, and occurrence of adverse events. No significant difference in terms of healing was found, either after 4 or after 8 weeks' treatment. Patients receiving lansoprazole experienced a greater improvement in heartburn after 4 weeks (p = 0.03), and there was a similar trend for acid regurgitation. Lansoprazole was found to be an effective and safe alternative to omeprazole in short-term treatment of moderate reflux oesophagitis. PMID- 8446847 TI - Different modes of fragmenting gallstones in extracorporeal shockwave lithotripsy. AB - Forty radiolucent gallbladder stones from eight patients were fragmented in vitro by extracorporeal shockwave lithotripsy, using the electromagnetic lithotripter Lithostar Plus (Siemens) at five different energy levels. The stones were characterized by size, computed tomography (CT) density, and cholesterol content. The largest residual fragment was measured after every 20 to 100 shock waves. As expected, fewer shock waves were required to achieve fragmentation at higher energy levels. When stones of the same size were compared, there were remarkable differences in the number of shock waves required for fragmentation. These differences must originate in other properties of the stones than size and number. Two different modes of fragmentation were observed: in one group of stones small, flat fragments were chipped off at the beginning of fragmentation ('chipping mode'). These stones initially lost about 25% of their weight as small fragments (< 1 mm) before breaking centrally into some large fragments. In the other group stones initially lost only about 10% of their weight as small fragments (< 1 mm) at the beginning of fragmentation and early broke centrally into some large fragments ('breaking mode'). Stones showing the chipping mode were almost pure cholesterol stones (> 97%) and required significantly less shock waves than stones of the same size showing the breaking mode (cholesterol content, 64-94%). This mode of fragmentation could not be predicted by CT density. PMID- 8446848 TI - Features of symptomatic gastroesophageal reflux in elderly patients. AB - Scarce information is available on gastroesophageal reflux disease in elderly patients. In this study we investigated patterns of gastroesophageal reflux and esophageal lesions in 24 elderly patients with typical gastroesophageal reflux symptoms and a mean age of 69 years (range, 65-76 years), as compared with 147 symptomatic younger patients with a mean age of 45 years (range, 21-64 years). The results of 24-h pH-monitoring and endoscopy showed that the elderly patients had pathologic reflux and reflux esophagitis more frequently than the young patients. The percentage time with pH < 4 in elderly patients with reflux esophagitis was 32.5% in 24 h, as compared with 12.9% in the younger patients with reflux esophagitis (P < 0.05). The elderly patients with reflux esophagitis had more prolonged periods of acid reflux in both the upright and supine positions than the younger patients. Endoscopy showed that 20.8% of elderly patients had grade III/IV esophagitis, whereas only 3.4% of younger patients had grade III/IV esophagitis (p < 0.002). The percentages of grade I/II esophagitis in the two groups were 12.5% and 26.5%, respectively (p < 0.002). We concluded that, compared with younger subjects, elderly patients have more severe gastroesophageal reflux and esophageal lesions. PMID- 8446849 TI - The Funen Adenoma Follow-Up Study. Characteristics of patients and initial adenomas in relation to severe dysplasia. AB - Between 1978 and 1992 a total of 1689 colorectal adenomas were removed in 1042 patients with no history of previous colorectal neoplasms. One hundred and eighteen patients had at least one adenoma with severe dysplasia. A 'clean colon' was ensured by total colonoscopy in 97% of the patients. A multiple logistic model was used to assess the independent risk factors associated with severe dysplasia. The size of largest adenoma and the extent of villous component were identified as independent patient risk factors associated with high risk of severe dysplasia. The results indicated that the risk of severe dysplasia is high in patients with large and/or villous adenomas and the risk is even higher when the adenomas are found in the sigmoid colon or rectum. PMID- 8446850 TI - Prophylaxis of gastrointestinal tract bleeding in patients admitted to a general hospital ward. Comparative study of sucralfate and cimetidine. AB - Gastrointestinal bleeding prophylaxis is well known in patients admitted to intensive care units, but only a few reports have analyzed this problem in patients admitted to a general hospital ward. In a previous study we demonstrated that close to 20% of such seriously ill placebo-treated patients bled. We conducted a prospective, randomized trial comparing cimetidine in a single dose of 800 mg and sucralfate at a dose of 1g/6h in a group of 139 patients from a cohort of 2010 patients consecutively admitted during a 10-month period to a department of internal medicine at a teaching hospital. The severity of their illness was assessed by the simplified acute physiologic score (SAPS). Gastrointestinal bleeding was assessed at the beginning of the study and daily during the hospitalization by means of Hemoccult paper tests or when frank hematemesis or melena occurred. Two of the 71 patients assigned to cimetidine and 2 of the 68 assigned to sucralfate presented with acute gastrointestinal bleeding, which was more severe in the sucralfate group. The drugs had similar safety profiles and were well tolerated, but the easier administration of cimetidine in a single dose, together with its low cost (25% less than sucralfate) argues in favor of cimetidine to prevent gastrointestinal bleeding in seriously ill patients admitted to general hospital wards. PMID- 8446851 TI - Decrease in contents of pancreatic carboxyl ester lipase, phospholipase A2, and lingual lipase in rats with streptozotocin-induced diabetes. AB - The changes in contents of pancreatic carboxyl ester lipase, phospholipase A2, and lingual lipase in rats with streptozotocin (STZ)-induced diabetes have been studied. The contents of pancreatic carboxyl ester lipase and phospholipase A2 decreased by 40% and 45%, respectively, 5 days after injection of STZ, whereas pancreatic lipase steadily increased to 100% over control. The content of lingual lipase decreased sharply by more than 90% 2 days after STZ injection, followed by a tendency to recover slightly. Insulin treatment at a dose abolishing the urine glucose in diabetic rats for 3 days restored the contents of pancreatic lipase, carboxyl ester lipase, and lingual lipase but not pancreatic phospholipase A2. The results indicate that lack of insulin action induces an anticoordinate change in gastrointestinal lipolytic enzymes, with decreases in pancreatic carboxyl ester lipase, phospholipase A2, and lingual lipase contents and an increase in pancreatic lipase content. PMID- 8446852 TI - Clinical, ultrasonographic, and roentgenographic study in 134 asymptomatic gallstone carriers. Is oral ursodeoxycholic acid treatment worthwhile? AB - We investigated retrospectively the ultrasonographic and roentgenographic characteristics of the gallstones and the gallbladder in 134 symptom-free carriers and evaluated prospectively the outcome and side effects of 6 to 24 months' ursodeoxycholic acid (UDCA) therapy in 36 individuals with silent stones. Two-thirds of the 134 subjects had multiple stones, and 71-75% had stones less than 15 mm in diameter. Gallstone calcification was detected in 13%. A non functioning gallbladder was observed in 19%, whereas gallbladder contraction was normal in 64 of 76 gallstone carriers. With regard to oral bile acid treatment, complete and partial dissolutions were achieved in 7 and 9 of 33 subjects, respectively (48.5%). Development of a non-functioning gallbladder occurred in 9%, and acquired gallstone calcification was seen in another 15%. We conclude that: i) the characteristics of the gallstones and the gallbladder are similar to those observed in symptomatic patients, and ii) UDCA therapy may be given in selected symptom-free carriers for no more than 6-12 months. Thereafter, it does not appear to be cost-effective. PMID- 8446853 TI - Comparison between the lactulose/mannitol and 51Cr-ethylenediaminetetraacetic acid/14C-mannitol methods for intestinal permeability. Frequency distribution pattern and variability of markers and marker ratios in healthy subjects. AB - Urinary excretion of lactulose and mannitol, determined by gas-liquid chromatography, was compared with that of 51Cr-ethylenediaminetetraacetic acid (EDTA) and 14C-mannitol for measurement of intestinal permeability in 28 healthy humans. The 0- to 6-h excretion values for unlabelled and labelled mannitol (marker of transcellular permeability) were normally distributed, whereas excretion values for lactulose and 51Cr-EDTA (markers of paracellular permeability) were skewly distributed, as were the lactulose to mannitol and 51Cr EDTA to 14C-mannitol ratios. Excretion of the transcellular markers but not of the paracellular markers was significantly correlated to urinary volume; correction for urinary volume resulted in decreased test variability. Significant correlation was found between lactulose and 51Cr-EDTA excretion (p < 0.01) and between mannitol and 14C-mannitol excretion (p < 0.001) but not between the lactulose to mannitol and 51Cr-EDTA to 14C-mannitol ratios (p = 0.11). Inter- and intraindividual test variability was greater for each chemically determined marker than for the corresponding isotope-labelled marker. Similarly, variability was greater for each paracellular marker than for the corresponding transcellular marker and for each paracellular/transcellular marker ratio than for the transcellular marker alone. Variability of mannitol excretion was increased by the frequent presence of food-derived mannitol in the urine. PMID- 8446854 TI - Effect of luminal exposure of oxidants on intestinal mucosal lipid peroxidation and absorptive function. AB - The lumen of the gastrointestinal tract is likely to have free iron and prooxidants that might generate free radicals, resulting in structural and functional damage to the absorptive cells. In the present study the effect of luminal exposure of different oxidants on intestinal mucosal lipid peroxidation and absorptive function in anaesthetized animals has been studied. Oxidants that require iron for free radical generation did not have any effect on the mucosa, whereas free radicals generated by using 2,2'azobis (2-amidino propane) dihydrochloride or menadione, which do not require iron, resulted in lipid peroxidation as assessed by malonaldehyde and conjugated diene formation and depletion of the antioxidant alpha-tocopherol. These oxidants also induced water and electrolyte secretion as studied by luminal perfusion. This observation is physiologically significant since the presence of prooxidants along with iron in the lumen may not have a damaging effect on the mucosa. PMID- 8446855 TI - Height, weight, and risk of colorectal cancer. An 18-year follow-up in a cohort of 5249 men. AB - The role of obesity in the risk of colorectal cancer is uncertain. We investigated the association between height and weight and the risk of colorectal cancer in an 18-year follow-up of 5249 employed men aged 40-59 years (mean, 48 years). Cancer of the colon was diagnosed in 51 men, and cancer of the rectum in 42 (all were adenocarcinomas). Adjusted for weight and age, the tertile of men with shortest height had a relative risk (95% confidence limits) of rectum cancer of 3.1 (1.0-9.0, p = 0.04), compared with the tallest tertile. Compared with the tertile of men who weighed the most, the tertile of men who weighed the least had an increased risk of 2.5 (0.9-6.9, p = 0.08) after adjustment for age and height. Compared with men who were in the highest tertile of both height and weight, the men in the lowest tertile of both height and weight had and increased risk of 5.5 (1.2-24.9, p = 0.02). There were no significant differences in height and weight between colon cancer cases and non-cases, but colon cancer cases had a significantly lower body mass index (kg/m2), 24.4 versus 25.3 (p = 0.03). Potentially confounding factors, such as smoking, alcohol, coffee consumption, physical activity on the job and in leisure time, and social class, had no influence on the results. We conclude that low height and low weight were strong predictors of rectal cancer, and that the least obese men had the highest risk of colon cancer. PMID- 8446856 TI - Annual meeting of the Swiss Society of Cardiology together with the Swiss Society of Aeronautic Medicine. Proceedings. Genf, 11-13 June 1992. PMID- 8446857 TI - Appropriateness of the use of cardiovascular procedures: a method and results of this application. AB - Resources available to provide adequate health care in western countries must compete with other priorities such as education and the environment. At the same time the allocation of health resources often does not correspond to the real needs of patients. We have developed a method that combines what is known in the literature with expert physician judgment to generate clinically valid appropriateness guidelines. The method involves a modified Delphi approach, including a detailed literature review, consultations with experts, and three rounds of panel ratings. Clinical scenarios, or indications, are rated appropriate, uncertain, or inappropriate. Appropriate means that the procedure is worth doing for the given indication if the health benefit exceeds the health risk. We have conducted panels relating to coronary procedures in four countries. Application of the indications to individual cases has demonstrated that the amount of inappropriate care is too large to be ignored. Dissemination of appropriateness results might take the form of public disclosure or as part of the physician/patient exchange to improve performance. Indications for which a procedure is frequently performed and which are rated uncertain should be considered to be the focus of controlled clinical trials. PMID- 8446858 TI - [Quality control of health care: epidemiological aspects]. AB - Quality control in health care should be performed by health professionals. To do so they must define indicators, set up studies aimed at measuring and analyzing quality of care, and implement quality assurance programs in health care systems. The elements of a quality improvement program of this kind are described, with special emphasis on the contribution of epidemiology in this field. PMID- 8446859 TI - [Risk of cardiological interventions]. AB - The risk of cardiac interventions has to be assessed in relation to the possible benefit and in comparison to the natural history and to alternative interventions. The relationship between complications (mortality, morbidity) and age, severity of the disease, gender and technique on one hand, and between risk of the intervention versus risk of uninfluenced natural history on the other, are discussed. Diagnostic, therapeutic and prophylactic interventions are presented separately; the benefit needs to be defined differently for each: diagnostic accuracy or symptom relief, improved quality of life and survival, and prolonged life respectively. Finally, it is stressed that the choice of an intervention is not only dependent on the determinants of risk, but also on the availability of a certain method, operator experience, cost and, last but not least, patient preference. PMID- 8446860 TI - On the options for the European cardiologist in the enlarging European Community. AB - In conclusion, European integration in 1992 will mean several things for the European cardiologist, the most important of which are the following: 1. The E.S.C. will and must be able to exert more influence than ever before on the legislative and executive processes in Brussels, now and in 1993, and therefore collectively in the partner countries. 2. Only then, like its American counterparts the A.C.C. and A.H.A., will the E.S.C. be able to join with the politicians to guide the all-important question of allotment of funds. Funds for patient care, teaching, research, advanced planning, for investments in hospitals and laboratories, are all part of our fight against heart disease. These can much better be applied for and allocated on a European scale than on a national basis. The mere avoidance of duplication and repetition may be the greatest benefit of integration. 3. Only by strengthening the E.S.C. with a "cadre" of experienced cardiologists we can deliver the expert manpower which this integrative process will require: "Let not our Society miss the opportunities which 1992 offers!" 4. As a final point, only when we, as a professional unit show that we can make choices, and desist from asking everything possible for every patient we see, will we be able to regain and retain the trust of the patient as well as the political representatives of our member nations. Let us capture this genie before it, too, escapes from the bottle (Braunwald, 1988). These points are symbolized in Figure 1. PMID- 8446861 TI - [Work load in occupations]. AB - Fewer subjects return to work after acute myocardial infarction or a cardiac surgical procedure than one would expect from the results of their medical examinations and cardiac tests. To decide whether a patient is able to return to work, one has to assess his individual prognosis and measure his maximal physical working capacity without cardiac dysfunction. Psychological and socioeconomic aspects have also to be considered. Recommendations are presented for practical procedure in assessing the ability of a patient to return to work. PMID- 8446862 TI - [Heart and sports in the daily life of a heart patient]. AB - Everyone should practice regular physical activity through life, with the aim of slowing down arterial damage due to aging. In cardiac patients, especially with coronary insufficiency, exercise is also a suitable method of rehabilitation and can thus be considered a complementary treatment when the situation has been restored by medication. Sport should be practised discriminately in quantity and quality to prevent its major complication, sudden death during effort. The arrhythmias that may be precursors of sudden death should be looked for in the stress test in particular. Pathologies involving a risk of sudden death should likewise be detected. Care should be taken to avoid anything in these patients that could predispose to onset of arrhythmia, which is very often the trigger for ventricular fibrillation. PMID- 8446863 TI - [Benefits of cardiac rehabilitation--a controversy]. AB - Cardiac rehabilitation is a comprehensive process of continuing care which takes place at different levels. Individual office-based care, out-patient group activities and in-patient programmes in specialized centres may be complementary or alternatively used according to the needs of individual patients. In Switzerland organized cardiac rehabilitation is available for 6000 patients per year. Formal rehabilitation programmes exert their beneficial effects mainly through exercise training, instruction in relaxation techniques as well as dietary and occupational counseling. These benefits are documented as an overall reduction of cardiovascular mortality by 20%, a slowing of disease progression, an improvement of physical work capacity, the modification of serum lipid fractions, and possibly improved psychosocial adjustment. Patients should be helped to accept coronary disease as a chronic disease, to maintain lifestyle changes in order to halt progression and to avoid complications while enjoying a meaningful life. Future improvements in Switzerland will include the careful selection of patients for the different forms and phases of rehabilitation, more extensive psychosocial counseling, continuity of care and the involvement of family members. PMID- 8446864 TI - [Who should perform echocardiograms?]. AB - This question falls into two parts: 1. Should echocardiography be reserved to cardiologists? We believe that only physicians with extensive training in cardiology and echocardiography are able to derive maximum information from echocardiograms. 2. Should echocardiography be performed by technicians, under the control and responsibility of well-trained physicians? This practice prevails in the majority of big centers in the United States. However, a study performed among the members of the Swiss Working Group of Echocardiography shows that this is rarely the case in Switzerland (14/145 = 10%). This situation has several reasons: most Swiss cardiologists think that echocardiography should be reserved to themselves, that their annual number of studies is not sufficient to warrant a technician, and/or that they are unable to find trained technicians. Experience of physicians used to working with technicians is however very positive. A prospective study reported here shows that the percentage of mistaken recordings or interpretations is low. Cooperation with well-trained technicians allows good quality work, saves the physicians' time, facilitates research projects and contributes to the training of future cardiologists in echocardiography. PMID- 8446865 TI - [Swiss pacemaker statistics of the years 1989, 1990 and 1991]. AB - In the annual pacemaker survey covering practically all pacemakers implanted in Switzerland (there have been 50 implanting hospitals in the last three years) the number of first implants increased from 242 per million population in 1989 to 252 in 1991. Clinical indications, ECG-indications and etiology have undergone no significant changes in the last three years. Within the pacing-systems used however there was a marked increase in rate responsive single chamber pacemakers from 25% in 1989 to 34% in 1991. The percentage of double chamber pacemakers however increased gradually from 14% in 1989 to 21% 1991. At the present time there are some 10,000 patients with a cardiac pacemaker in this country. PMID- 8446866 TI - [Indications for coronary dilatation and bypass surgery]. AB - Coronary artery disease is the dominant disorder in industrialized countries. It can be treated by drugs, coronary angioplasty, or bypass surgery. Angioplasty has become the most frequent mode of active therapy. Local variations in the use of treatment modalities can be explained mainly by early detection of coronary artery disease yielding more candidates for angioplasty. All indications should be based on a combination of symptoms, objective signs of ischemia (e.g., stress test) and angiographic correlates. Coronary angioplasty is limited to the less complex cases such as single vessel disease (except for diffuse disease, old total occlusions), double vessel disease with up to 3 discrete lesions or lesions in secondary vessels, and, exceptionally, triple vessel disease of the appropriate kind (usually in 2 sessions). These limitations arise from the drawbacks of the method, i.e., acute occlusion (about 7%), recurrence (about 30%), and technical failures (about 5%). For acute myocardial infarction, direct coronary angioplasty is probably the method of choice, provided it can be performed within 30 minutes after diagnosis. For unstable angina, the results are inferior to those obtained with stable symptomatology; compared with the spontaneous prognosis, they remain nonetheless beneficial. The same holds true for angioplasty in elderly patients, where the reduced chances of success must be viewed in light of a typically very severe clinical picture. Angioplasty is often a blessing for young patients. It allows immediate resumption of a normal life and is easily repeatable over the years. Indications for coronary bypass surgery should not be deduced from the randomized studies of the seventies. They concentrated on survival, and surgical methods have been refined since.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446867 TI - [Outcome and analysis of participation in the 2d MONICA survey (1988-1989) of cardiovascular risk factors]. AB - Two Swiss regions, the cantons of Vaud and Fribourg (VD-FR) and the canton of Ticino (TI), take part in the international research project MONICA (MONItoring trends and determinants in CArdiovascular disease). In this framework, two surveys were respectively carried out in 1984-86 and in 1988/89 to determine the distribution of the major cardiovascular risk factors in the adult population. This article presents the outcome of the sampling procedure and participation for the second survey. A two-stage sampling procedure was performed by randomly drawing first communes (51 in VD-FR region; 25 in TI region) and then individuals out of the communal registry offices (3300 in VD-FR; 2000 in TI). In the two regions, 2011 and 1458 persons respectively attended the medical examination, leading to overall participation rates of 61% and 73%. As the sex and age distribution of the sample and of the participants is very close to that of the population, a major selection bias is unlikely. For the VD-FR region, the improvement in the participation (57% in the first survey) is due mainly to a better response from foreign nationals and older persons, whereas in the TI region the drop in recruitment (78% in the first survey) may reflect a saturation point reached by the population after several years of an intensive prevention programme against coronary heart disease initiated in 1984. In both regions, unmarried people represent the only population group in which the participation rate has decreased. On the basis of a questionnaire proposed to the non participants, unmarried status, sedentary leisure activities and a previous cholesterol check appear as factors significantly associated with a higher refusal rate. PMID- 8446868 TI - [Smoking, blood pressure and body weight in the Swiss population: MONICA study 1988-89]. AB - Two Swiss regions, the cantons of Vaud and Fribourg (VD-FR) and the canton of Ticino (TI), take part in the international research project MONICA (MONItoring trends and determinants in CArdiovascular disease). In this framework, three surveys are planned to monitor the prevalence of the principal risk factors. The second survey was carried out in 1988/89 on 2011 participants aged 25 to 74 for the VD-FR region and on 1458 participants aged 35 to 64 for the TI region. This article is devoted to the results concerning smoking habits, blood pressure, body height and weight. In the VD-FR region, the percentage of regular smokers steadily decreases with age, from 44% for men and 36% for women in the 25-34 age group to 15% and 10% respectively in the 65-74 age group. Inversely, the proportion of participants with high blood pressure rises steeply with age from nearly zero in the 25-34 group to more than a quarter in the 65-74 group. Similar risk factor levels are observed in the TI region. Two significant trends show up in comparison with the first survey (1984-86) for the latter region: the decreases in mean blood pressure levels for both sexes and in the proportion of regular smokers for men. However, these trends are to be interpreted cautiously because of potential measurement bias between surveys. PMID- 8446869 TI - [Blood lipids in the Swiss population: MONICA study 1988-89]. AB - The second population survey of the Swiss MONICA project took place in 1988-89 in the cantons of Vaud, Fribourg and Ticino. Blood lipids (total, LDL, and HDL cholesterol as well as apolipoproteins A-I and B) were measured in 3341 individuals aged 25-74 years belonging to a representative sample of the three cantons' population. Total and LDL cholesterol values were high on average, especially among patients aged 45 and over: total cholesterol was > 6.5 mmol/l in 27% (age 25-34) to 58% (age 45-54) and in 15% (age 25-34) to 64% (age 65-74) of men and women, respectively. HDL cholesterol values were relatively stable with age, at a higher level in women (median 1.5 mmol/l) than in men (median 1.2 mmol/l). To summarize, about 1 out of 5 people had cholesterol values placing them at low risk for the development of coronary heart disease, whereas 1 out of 4 were at increased risk. Apolipoprotein B, a component of LDL cholesterol, and apolipoprotein A-I, a component of HDL cholesterol, were measured for the first time in a large representative sample of the Swiss population. The distribution of both apolipoproteins was, in the aggregate, very similar to the distribution of the corresponding LDL and HDL cholesterol. A comparison of cholesterol values measured in 1988-89 with values previously measured in the same population (MONICA population survey 1984-85) did not show any reduction with time. PMID- 8446870 TI - [Prevalence of cardiovascular risk factors in the Basel city population 1989 1990]. AB - In the Swiss canton of Basel-Stadt, the levels of the major cardiovascular risk factors were measured in 1989/90 in a representative sample of 533 inhabitants (252 men and 281 women) aged 25 to 74. Some sex and age specific results concerning blood pressure, height, weight, body-mass index (BMI), cholesterol and smoking status are presented in the article. For the participants aged 35 to 64, the age-standardized (reference population: Switzerland 1989) prevalence rates are always higher for males than for females. High blood pressure (systolic over 160 mm Hg or diastolic over 95 mm Hg) is observed in 17% of the men and 12% of the women, whereas an elevated cholesterol level (over 6.5 mmol/l) concerns respectively 39% and 28% of them. Regular cigarette smokers represent 30% of the males and 27% of the females. Overweight is found in 27% of the men (BMI > or = 27.8 kg/m2) and in 18% of the women (BMI > or = 27.3 kg/m2). These results can be compared to those of the second population survey of the MONICA study carried out in 1988/89 in two other Swiss regions, keeping in mind that there are some methodological differences between the two studies. Overall, high blood pressure appears to be more frequent and hypercholesterolemia less common in Basel. PMID- 8446871 TI - [Regular assessment of cardiovascular risk factors and diseases: a valuable tool or not? (The MONICA experience)]. AB - An important aspect of public health policy is the information system through which the health of the whole population and of particular groups at risk can be monitored. In Switzerland, a first national health survey (SOMIPOPS) was carried out in 1981-1982 by questionnaire and interview and paved the way for implementation of the Swiss Health Survey, whose first test run is currently ongoing. Periodic health examination surveys including measurements of physical characteristics have been conducted only at a regional level in the framework of the WHO project MONICA (MONItoring of trends and determinants in CArdiovascular disease). The mainly French-speaking cantons of Vaud and Fribourg and the Italian speaking canton of Ticino take part in this project and the levels of the major cardiovascular risk factors were measured on representative samples of the population in 1984-86 and in 1988-89. A similar survey was conducted in the German-speaking city of Basel in 1989/89. These studies allow time trend and geographical analysis, and some comparisons are presented in terms of age standardized prevalence rates of the risk factors. The discussion focuses on the desirability of implementing a periodic health examination survey at the national level. One main advantage of such surveys is that variables of particular interest at a given time can be added to the usual set of measurements, as was the case for blood lead, vitamin D and apolipoproteins in the MONICA surveys. PMID- 8446872 TI - ["Help--or at least do no harm"]. PMID- 8446873 TI - [Age-related changes in the pulp chamber and its wall in human canine teeth]. AB - A total of 21 extracted, vital human canines (i.e., 8 maxillary and 13 mandibular) of patients between 40 and 78 years of age has been used to study, by means of X-rays and scanning electron microscopy, the age-related restriction of the pulp chamber and of the root canal, and the structure of its inorganic dentinal walls. This was done at the mesial and distal as well as the vestibular and oral aspects of the pulp chamber walls. In addition, the density of the openings of the dentinal tubules was, under standardized conditions, determined at the coronal part of the pulp chamber, in the middle of the root canal and apically on each of the four aspects of the pulp chamber, i.e. vestibularly, mesially, orally and distally. The results demonstrated that (1) pulp chamber and root canal of both maxillary and mandibular canines, with increasing age of the patients, does not become very much restricted in the vestibulo-oral direction and only very little or patchwise in the mesio-distal direction, (2) fibrodentin that causes such restriction, is deposited in greater amounts only after 60 to 70 years of age, and (3) the density of the tubules is very variable, rather similar in the coronal crown chamber and the middle of the root canal, both mesio distally and vestibulo-orally, and decreases sharply towards the root apex. These findings are discussed mainly with respect to the age-related changes in the pulp chamber and root canals of human central and lateral incisors. PMID- 8446874 TI - [Does the application of a fluoride lacquer modify the de- and remineralization of initial carious lesions in vitro?]. AB - Bovine enamel specimens with artificial initial lesions were fluoridated with a fluoride lacquer (Duraphat) for 6 hours. Subsequently artificial plaque (Streptococcus mutans, FA1) was grown on the enamel blocks in an artificial mouth. During the experimental period (23 days) the specimens were continuously rinsed with synthetic saliva and with sucrose twice daily. Nonfluoridated specimens served as controls. At the end of the experiment microhardness was evaluated in three levels parallel to the enamel surface. In addition, the concentration of KOH-soluble and structurally bound fluoride was determined. In the fluoridated specimens microhardness increased in levels near the surface of the lesion, but decreased in the next two lower levels. However, in the nonfluoridated enamel specimens microhardness decreased in all three levels and was more pronounced compared to the fluoridated specimens. At the end of the experiment no KOH-soluble fluoride could be determined on the surfaces of the artificial lesion. In contrast, structurally bound fluoride was significantly increased in the fluoridated specimens. A single application of the fluoride lacquer on initial enamel lesions resulted in remineralization of the outer enamel layers even under persisting cariogenic conditions. However, lesion progression could not be inhibited totally. PMID- 8446875 TI - [The results of caries prophylaxis after 25 years of the School Dental Clinic in the city of St. Gallen]. AB - Since 1966 the School Dental Clinic of St. Gall has been in charge of preventive dentistry and treatment of school and kindergarten children. For children from kindergarten and the 1st level of primary school, the caries incidence rate was established in percentages. For those of 14 years of age, the DFM-T index (including 2 bit-wings) was determined. For the 14-year-old children the average number of carious, filled and extracted teeth (DMF-teeth) decreased as follows: 1974 DFM-T = 7.0; 1978 DMF-T = 5.0; 1982 DMF-T = 3.0; 1987 DMF-T = 2.7; 1991 DMF T = 1.1. The percentage of children with a healthy natural dentition in this age group was approximately 40% in 1991. The number of extractions of permanent teeth dropped 15 times, the number of required tooth fillings up to 5 times. Whilst children of 14 years of age in 1991 showed a minimum of carious lesions, the caries prevalence of kindergarten children and those of 1st level primary school increased slightly (partly due to influx of foreigners). This fact draws attention to the significance of a uniform, continuous and systematic prevention in the future. PMID- 8446876 TI - [The relationships between orthodontics and temporomandibular joint dysfunction. A review of the literature and longitudinal study]. AB - The fist part of this study concerns a literature review on temporomandibular dysfunction (TMD). There exists an equal amount of literature relating occlusal interferences to TMD, as there are reports denying any causal relationship. It is remarkable, however, that the latter reports are relatively recent. The relationship between the Angle classification and TMD is reported to be only weak in a "normal" orthodontic population. The relationship between morphologic malocclusion, e.g. deep bites or crossbites, with TMD seems to be somewhat stronger. The vast majority of the reports did not find any relationship between TMD and orthodontic treatment or extractions. Our own longitudinal prospective study could not reveal any systematic relationship between orthodontic treatment or extractions and TMD. PMID- 8446877 TI - The hygiene-promoting concept of practice (I). The legal bases and organization of the practice. The Commission for Hygiene in Practice of the Societe Suisse d'Odonto-Stomatologie. PMID- 8446878 TI - [The implant and GTR. The use of the implant and GTR for the integral preservation of a partial denture following root fracture]. PMID- 8446879 TI - Virtuous viruses. Agents of disease are being turned against cancer. PMID- 8446880 TI - Obstacle course. Funding and policy stifle contraceptive research. PMID- 8446881 TI - The aging of the human species. PMID- 8446882 TI - Listening with two ears. PMID- 8446883 TI - The evolution of virulence. PMID- 8446884 TI - Modern humans in the Levant. PMID- 8446885 TI - Problems encountered assessing AIDS awareness among rural Mid-West high school students in a family practice setting. AB - There has been growing interest in assessing AIDS awareness and knowledge of risk behavior among teenagers and how to measure the effectiveness of HIV education programs. A survey modeled after the CDC assisted study was distributed to three populations of high school students within a mid-western community to compare results with the CDC urban sites. Of 186 surveyed, the area results were comparable to urban sites and generally evidenced superior AIDS knowledge and lower incidence of high risk behavior. Ignorance and high risk behavior in rural areas warrants HIV education programs. The survey showed 58.6% of high school students regard their family physician as a primary source of AIDS information. PMID- 8446886 TI - Guidelines in transfusions--what's new? PMID- 8446888 TI - Child abuse by poisoning. PMID- 8446887 TI - The great enigma: sex as it relates to emotional stability, physical pleasure and a productive life. PMID- 8446889 TI - Smitten by quail. PMID- 8446890 TI - Splicer RNAs. PMID- 8446891 TI - Empathy and brain evolution. PMID- 8446892 TI - The risks of inbreeding. PMID- 8446893 TI - New meetings tackle the knowledge conundrum. PMID- 8446894 TI - The cell's nucleus shapes up. PMID- 8446895 TI - MS study yields mixed results. PMID- 8446896 TI - GTP hydrolysis in protein synthesis: two for Tu? PMID- 8446897 TI - Crystal structure of a synthetic triple-stranded alpha-helical bundle. AB - The x-ray crystal structure of a peptide designed to form a double-stranded parallel coiled coil shows that it is actually a triple-stranded coiled coil formed by three alpha-helices. Unlike the designed parallel coiled coil, the helices run up-up-down. The structure is stabilized by a distinctive hydrophobic interface consisting of eight layers. As in the design, each alpha-helix in the coiled coil contributes one leucine side chain to each layer. The structure suggests that hydrophobic interactions are a dominant factor in the stabilization of coiled coils. The stoichiometry and geometry of coiled coils are primarily determined by side chain packing in the solvent-inaccessible interior, but electrostatic interactions also contribute. PMID- 8446898 TI - A mixed-valent polyiron oxo complex that models the biomineralization of the ferritin core. AB - A novel polyiron oxo complex, [FeIII4FeII8(O)2(OCH3)18(O2CCH3)6(CH3OH) 4.67] (1), has been prepared from ferrous acetate and lithium methoxide in methanol by slow addition of dioxygen. The three-dimensional close-packed layered structure found in 1 closely mimics that proposed for the inorganic core in the iron storage protein ferritin. The Mossbauer spectra of 1 reveal superparamagnetic relaxation at temperatures below 15 K, a property characteristic of the ferritin core. The small size and mixed-valent nature of 1 suggest that it is a reasonable model for intermediates formed in the biomineralization of iron during ferritin core formation. A related compound, with the same iron-oxygen framework found in 1 but containing only two ferric ions, has also been structurally characterized. Because the clusters exhibit properties of both discrete molecules and extended solids, they are representative of a new class of nanometer-sized compounds that bridge the molecular solid-state boundary. PMID- 8446899 TI - Toward a model for the interaction between elongation factor Tu and the ribosome. AB - In the elongation cycle of bacterial protein synthesis the interaction between elongation factor-Tu (EF-Tu).guanosine triphosphate (GTP), aminoacyl-transfer RNA (aa-tRNA), and messenger RNA-programmed ribosomes is associated with the hydrolysis of GTP. This interaction determines the selection of the proper aa tRNA for incorporation into the polypeptide. In the canonical scheme, one molecule of GTP is hydrolyzed in the EF-Tu-dependent binding of aa-tRNA to the ribosome, and a second molecule is hydrolyzed in the elongation factor-G (EF-G) mediated translocation of the polypeptide from the ribosomal A site to the P site. Substitution of Asp138 with Asn in EF-Tu changed the substrate specificity from GTP to xanthosine triphosphate and demonstrated that the EF-Tu-mediated reactions involved the hydrolysis of two nucleotide triphosphates for each Phe incorporated. This stoichiometry of two is associated with the binding of the correct aa-tRNA to the ribosome. PMID- 8446900 TI - Association between brain temperature and dentate field potentials in exploring and swimming rats. AB - Attempts to correlate behavioral learning with cellular changes, such as increased synaptic efficacy, have often relied on increased extracellular potentials as an index of enhanced synaptic strength. A recent example is the enlarged excitatory field potentials in the dentate gyrus of rats that are learning spatial relations by exploration. The altered hippocampal field potentials do not reflect learning-specific cellular changes but result from a concomitant rise in brain temperature that is caused by the associated muscular effort. Enhanced dentate field excitatory potentials followed both passive and active heating and were linearly related to the brain temperature. These temperature-related effects may mask any learning-induced changes in field potential. PMID- 8446901 TI - Higher level organization of individual gene transcription and RNA splicing. AB - Visualization of fibronectin and neurotensin messenger RNAs within mammalian interphase nuclei was achieved by fluorescence hybridization with genomic, complementary DNA, and intron-specific probes. Unspliced transcripts accumulated in one or two sites per nucleus. Fibronectin RNA frequently accumulated in elongated tracks that overlapped and extended well beyond the site of transcription. Splicing appears to occur directly within this RNA track, as evidenced by an unambiguous spatial separation of intron-containing and spliced transcripts. Excised introns for neurotensin RNA appear free to diffuse. The transcription and processing site of the fibronectin gene localized to the nuclear interior and was associated with larger transcript domains in over 88 percent of the cells. These results support a view of nuclear function closely integrated with structure. PMID- 8446902 TI - A three-dimensional view of precursor messenger RNA metabolism within the mammalian nucleus. AB - A quantitative three-dimensional analysis of nuclear components involved in precursor messenger RNA metabolism was performed with a combination of fluorescence hybridization, immunofluorescence, and digital imaging microscopy. Polyadenylate [poly(A)] RNA-rich transcript domains were discrete, internal nuclear regions that formed a ventrally positioned horizontal array in monolayer cells. A dimmer, sometimes strand-like, poly(A) RNA signal was dispersed throughout the nucleoplasm. Spliceosome assembly factor SC-35 localized within the center of individual domains. These data support a nuclear model in which there is a specific topological arrangement of noncontiguous centers involved in precursor messenger RNA metabolism, from which RNA transport toward the nuclear envelope radiates. PMID- 8446903 TI - The role of water in hemoglobin function and stability. PMID- 8446904 TI - A 39-year-old man with chronic hepatitis, elevated serum ferritin values, and a family history of hemochromatosis. AB - The patient described is a heterozygote for hemochromatosis, and he has chronic hepatitis C. We have hypothesized that, because of chronic viral hepatitis, he could either have an increase in circulating NTBI or he could have up-regulation of hepatocyte TfR expression, perhaps caused by a viral effect on the IRE of TfR mRNA, or a combination of both. Either could result in an increase of his hepatocellular iron uptake, resulting in a redistribution of his total body iron burden (which is in the range seen for HHC heterozygotes) and, in effect, "concentrating" the iron in his liver, thus simulating homozygous HHC. It is likely that there are interrelationships between hepatic iron concentration, hepatocellular iron metabolism, and chronic viral hepatitis. Understanding of these interrelationships may be important in the understanding of some of the fundamental mechanisms of viral growth and replication and hepatocellular injury. A clearer understanding of these interactions is necessary to diagnose the cause of liver disease accurately in patients such as this one. PMID- 8446905 TI - Parenchymal and nonparenchymal cell interactions in the liver. PMID- 8446906 TI - Morphologic investigation of sinusoidal cells. PMID- 8446907 TI - Quantification of sinusoidal cell function in vivo. AB - Although the clearance and distribution of ligand molecules in circulation represent the function of hepatic sinusoidal cells, these mechanisms revealed a network that is more intricate than would at first seem, since several receptors are common to not only one type of cell, but also to two or three types of cells in the liver. In the case of latex particles in which their uptake by a particular cell type seems to be determined by their size, sinusoidal endothelial cells are able to internalize particles up to 0.23 microns under physiologic conditions, in vivo, and larger particles are taken up by Kupffer cells. However, when the phagocytic function of Kupffer cells is impaired by frog virus 3 or alcohol, endothelial cells have been found to take up particles larger than 1 micron in diameter after the injection of an excess amount of latex particles. Endothelial cells would thus constitute a second line of defense in the liver in that they remove foreign materials from the blood when Kupffer cell phagocytic function is totally disturbed. This potential role may not, however, be fully expressed under physiologic conditions when Kupffer cells are active in clearing foreign substance from the circulation. The functions of liver sinusoidal cells are varied and complex and these cells can be regarded as "a sinusoidal cell unit." This cellular interaction must be taken into account for any quantitative analysis. PMID- 8446908 TI - Kupffer cells: their activation and role in animal models of liver injury and human liver disease. PMID- 8446909 TI - Role of periportal and perivenous sinusoidal endothelial cells in hepatic homing of blood and metastatic cancer cells. PMID- 8446910 TI - Liver-associated lymphocytes: role in tumor defense. PMID- 8446911 TI - Role of sinusoidal lining cells in hepatic reperfusion injury following cold storage and transplantation. PMID- 8446912 TI - Epidemiology methods to assess occupational exposures and pregnancy outcomes. PMID- 8446913 TI - An overview of occupational medicine. PMID- 8446914 TI - The use of available data sets to define the safety of occupational chemical exposures during pregnancy. PMID- 8446915 TI - Preterm labor and delivery in working women. PMID- 8446916 TI - Counseling for occupational exposures and reproductive risks. PMID- 8446917 TI - Physical agents in the workplace. PMID- 8446918 TI - Fetal protection policies in the United States. PMID- 8446919 TI - MK-801, phencyclidine (PCP), and PCP-like drugs increase burst firing in rat A10 dopamine neurons: comparison to competitive NMDA antagonists. AB - Extracellular single-unit recordings were used to assess the effects of PCP and PCP-like drugs (MK-801 and TCP) on the burst firing of ventral tegmental A10 dopamine neurons in the rat. The effects of these noncompetitive N-methyl-D aspartate (NMDA) receptor antagonists were compared to the potent and competitive NMDA antagonists CGS 19755 and (+/-)CPP, and to BTCP, a PCP-derivative possessing little affinity for the PCP binding site within the ion channel gated by NMDA. PCP, MK-801, and TCP produced dose-dependent increases in the firing rate, which were accompanied by increases in the amount of burst activity, the number of action potentials within a burst, and the conversion of nonbursty cells to bursty. However, the coefficient of variation, a measure of the regularity of firing, was not significantly altered. These predominately excitatory effects contrast with the inhibition of firing, decrease in bursting, and regularization of pattern produced by BTCP. CGS 197555 and (+/-)CPP failed to alter any of the measured parameters. Thus, the increase in firing rate and amount of burst activity of dopamine neurons produced by PCP and PCP-like drugs, and the resultant hyperdopaminergia within the mesolimbic-mesocortical regions, could underlie the psychotomimetic properties of these compounds. Moreover, this effect would not appear to be related to a loss of activity at the NMDA recognition site, as evidenced by the lack of effect of the competitive NMDA antagonists. PMID- 8446920 TI - Comparison of the effects of the cholecystokinin-B receptor antagonist, PD 134308, and the cholecystokinin-A receptor antagonist, L-364,718, on dopamine neuronal activity in the substantia nigra and ventral tegmental area. AB - Extracellular single-unit recording techniques were used to study the effects of the cholecystokinin-A (CCK-A) antagonist, L-364,718, and the CCK-B antagonist, PD 134308, on DA neuronal activity in chloral hydrate anesthetized rats. Neither L 364,718 (0.1-1.6 mg/kg i.v.) nor PD 134308 (0.1-6.4 mg/kg) altered the basal firing rate of substantia nigra or ventral tegmental area DA neurons. The ability of PD 134308 and L-364,718 to alter the apomorphine-induced inhibition of substantia nigra DA neurons was assessed. Pretreatment with L-364,718 (0.6 or 4.16 mg/kg i.v.) did not shift the apomorphine dose-response curve (0.5-32 micrograms/kg i.v.). In contrast, PD 134308 (0.6 or 6.4 mg/kg i.v.) produced dose related, significant shifts to the right of the apomorphine dose-response curves. However, these effects were small in comparison to the haloperidol (0.1 mg/kg i.p.)-induced shift of the apomorphine curve. These data suggest that in the substantia nigra there may be a tonic level of CCK release that, through actions on CCK-B receptors, may modulate DA agonist-induced inhibition of DA neuronal activity. PMID- 8446921 TI - LSD has high efficacy relative to serotonin in enhancing the cationic current Ih: intracellular studies in rat facial motoneurons. AB - The effects of LSD (d-lysergic acid diethylamide) on rat facial motoneurons were compared to those of 5-hydroxytryptamine (5-HT) in brain slices by means of current clamp and single-electrode voltage-clamp recordings. As previously reported, 5-HT, in part by decreasing a resting potassium conductance, produced a reversible depolarization (approximately 5 mV), an increase in input resistance, and an enhancement in electrical excitability. LSD also produced an increase in electrical excitability, although with a much slower onset and longer duration. However, in contrast to 5-HT, LSD produced only a slight depolarization (1-2 mV). Moreover, in the presence of LSD the depolarizing effect of 5-HT was markedly attenuated. The 5-HT2/5-HT1C agonist 1-(2,5-dimethoxy-4-iodophenyl)-2 aminopropane (DOI) produced effects intermediate between LSD and 5-HT. The LSD induced increase in electrical excitability was completely reversed by spiperone, a 5-HT2/5-HT1A antagonist, and by ritanserin, a 5-HT2/5-HT1C antagonist; the effects of 5-HT were also reduced by these 2 antagonists, but complete blockade did not occur at the concentrations and durations tested. Surprisingly, LSD was found to enhance the hyperpolarization-activated nonspecific cation current Ih to a greater extent than did 5-HT; this enhancement was blocked by both spiperone and ritanserin. These results indicate that, despite having low efficacy relative to 5-HT in decreasing resting potassium conductance, LSD has high efficacy in enhancing the Ih current in rat facial motoneurons; possible mechanisms for this difference are discussed. PMID- 8446922 TI - Physiological and morphological properties of accumbens core and shell neurons recorded in vitro. AB - The morphology and electrophysiological properties of neurons in the nucleus accumbens were studied using intracellular recording techniques in rat brain slices maintained in vitro. Neurons were subdivided according to their location in the shell or core region of the nucleus accumbens. Most of the cells in both regions had small to medium-sized (15.8 +/- 2.8 microns) somata with densely spinous dendrites, somewhat similar to the striatal medium spiny neuron. However, minor morphological differences between neurons from accumbens core and shell regions were found, such as fewer primary dendrites in shell neurons than in the core (3.8 +/- 0.8 vs. 4.4 +/- 1.0) and the spatial organization of their dendritic trees. In general, the passive membrane properties of neurons in each region were similar. However, shell neurons appeared to be less excitable in nature, as suggested by (1) a faster time constant, (2) the absence of TTX insensitive events resembling low-threshold spikes, and (3) the lower probability of evoking spikes in shell neurons by stimulation of amygdaloid or cortical afferents in comparison to the responses of core neurons to cortical afferent stimulation. In most nucleus accumbens neurons the action potentials evoked by membrane depolarization were preceded by a slow Ca(2+)-dependent depolarization and showed firing-frequency adaptation. Following TTX administration, all-or-none spike-like events resembling high-threshold calcium spikes were observed in both regions. In summary, except for minor differences, most of the properties of core and shell neurons are similar, supporting their characterization as subdivisions of a single structure. Therefore, differences in the functional properties of these neuronal populations are likely to be due to their distinct connectivity patterns. PMID- 8446923 TI - Light and electron microscopic localization of calcitonin gene-related peptide immunoreactivity in lamina II of the feline trigeminal pars caudalis/medullary dorsal horn: a qualitative study. AB - Calcitonin gene-related peptide (CGRP) is a neuropeptide that is associated with a subset of primary afferent fibers and appears to have a role in nociception. The purpose of the present study was to perform a qualitative light, and especially electron microscopic (LM and EM), examination of CGRP-immunoreactivity (IR) within lamina II (substantia gelatinosa) of the feline pars caudalis/medullary dorsal horn (PC/MDH) of the spinal trigeminal nucleus. The LM investigation revealed massive CGRP-IR within lamina II outer, with fewer fibers that traversed lamina II inner. The EM preparations showed CGRP-IR in small, thinly myelinated and unmyelinated axons, preterminal axons, and in axon terminals that formed asymmetric synaptic contacts onto small dendritic profiles. The terminals with CGRP-IR were often the central element within glomeruli, where the terminal usually formed 2 or more asymmetric synaptic specializations onto 1 or more dendrites. Many of these postsynaptic dendrites contained synaptic vesicles. Other profiles were seen forming presynaptic contacts onto the terminal with CGRP-IR, and these profiles most likely represent presynaptic dendrites and/or other axon terminals of intrinsic origin. The synaptic association of terminals showing CGRP-IR with vesicle-containing dendrites, presynaptic dendrites, and/or other axon terminals suggests that terminals with CGRP-IR are especially susceptible to modulation. PMID- 8446924 TI - Fetal dexamethasone exposure interferes with establishment of cardiac noradrenergic innervation and sympathetic activity. AB - Endogenous glucocorticoids provide natural differentiation signals for adrenergic neurons, and exposure to high exogenous steroid levels thus disrupts the timing of neuronal maturation. In the current study, pregnant rats were given 0.05, 0.2, or 0.8 mg/kg dexamethasone on gestational days 17, 18, and 19, and the effects on development of cardiac sympathetic function were assessed postnatally in the offspring. Dexamethasone produced a dose-dependent retardation of body and heart weight gains; at the highest dose, heart weight deficits were smaller than those for body weight, producing a relative cardiomegaly. The weight effects were accompanied by abnormalities of noradrenergic innervation, as assessed with measurements of norepinephrine levels and turnover. Norepinephrine levels were significantly reduced at all doses of dexamethasone, with the magnitude of effect exceeding that on heart or body weights; thus the levels were reduced even when corrected for tissue weight (ng norepinephrine/g heart weight). Norepinephrine turnover, a measure of neuronal impulse activity, showed delayed development at the lowest dose of dexamethasone and displayed profound suppression throughout development at the higher doses. Adverse effects of dexamethasone on norepinephrine turnover were still apparent in young adulthood, despite the recovery of weight variables to within 15% of normal values. In light of the release of steroids during maternal stress and the use of steroids in the therapy of neonatal respiratory distress, developing adrenergic neurons are likely to be targeted for adverse effects even when standard growth indices have normalized. PMID- 8446926 TI - Evaluation of congenital limb reduction defects in upstate New York. AB - Limb reduction defects (LRD), reported to the Congenital Malformations Registry in upstate New York between 1983-1987, were investigated in terms of LRD classification, parental demographics, and LRD characteristics. After excluding LRD with chromosome abnormalities, we followed guidelines developed by the European Congenital Anomaly Surveillance Consortium (EUROCAT) to classify 271 LRD into six groups based on similar patterns of embryological failure. The descriptive analysis indicated a prevalence of 0.45 per 1,000 births (stable over 5 years) for LRD diagnosed during the first 2 years of life. Among 271 LRD cases, 95 were classified as terminal transverse (35.1%), 71 as split limbs (26.2%), 36 as preaxial (13.3%), 32 as postaxial (11.8%), 26 as intercalary (9.6%), and 11 as multiple types (4.1%). In cases with multiple limb involvement (28.4%), two thirds had the same type of LRD in each limb. The multiple types and preaxial groups showed the most distinctive characteristics: they had the highest frequency of suspected syndromes, other birth defects, and syndactyly compared to the other LRD. There were no significant differences in the distribution of demographic variables among different LRD types. Consideration of the incidence and characteristics of LRD by classifying them into these distinct subgroups may be useful for evaluating possible mechanisms of malformation. PMID- 8446925 TI - Nitrofen-induced congenital diaphragmatic defects in CD1 mice. AB - In previous clinical reports, we have documented the association of several morphologic changes with congenital diaphragmatic hernia or, perhaps more appropriately termed, congenital diaphragmatic defect (CDD). These anomalies include decreased cardiac mass with left ventricular hypoplasia in infants with left-sided CDDs (Siebert et al., '84), enlarged, asymmetric chests (Siebert and Benjamin, '87), and extrathoracic anomalies (Benjamin et al., '88), including urinary tract anomalies and elevated kidney weights in otherwise normal kidneys (Glick et al., '90; Siebert et al., '90). Hypoplastic lungs and hearts and enlarged chests are thought to result from the herniation of abdominal viscera into the thoracic cavity, but for the renal abnormalities, pathogenesis is unclear. The findings are intriguing, for they could mirror unrecognized developmental relationships between the diaphragm, lung, heart, and kidney. In order to further examine these issues and to test the applicability of experimentally produced CDDs to human disease, we administered nitrofen (2,4 dichlorophenyl-p-nitrophenyl ether), an herbicide known to produce diaphragmatic defects in rodents, to time-mated CD1 mice by gavage feeding on gestational days 8 and 9. Dosages were 200 (low dose) or 500 (high dose) mg/kg body weight, and fetuses were studied on gestational day 18. Diaphragmatic defects occurred in a dose-response fashion: 0% (0/48) control or sham-fed, 5% (5/104) in the low-dose group, and 25% (19/75) in the high-dose group. Several fetuses with cleft palate, renal agenesis, exencephaly/encephalocele, and/or Di-George sequence were noted at the high dose, the latter a previously undescribed finding. Diaphragmatic defects were primarily right sided and only associated with herniation of abdominal viscera in animals exposed to 500 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446927 TI - HMG-CoA reductase mRNA in the post-implantation rat embryo studied by in situ hybridization. AB - 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (EC 1.1.1.34) is the rate limiting step in the mevalonate pathway that produces isoprenoids and cholesterol. Inhibitors of HMG-CoA reductase are teratogenic in vivo and induce neural tube defects in rat embryo culture, effects which appear unrelated to cholesterol deficiency. This study is the first to localize HMG-CoA reductase mRNA by in situ hybridization (ISH). Expression of reductase mRNA was examined in post-implantation rat embryos, and for control purposes in rat liver and UT-1 cells, using a digoxigenin-11 (dig-11) labelled cRNA probe. Eighteen-day fetal liver showed heavy but patchy hybridization, and adult rat liver showed strong hybridization only on some periportal hepatocytes, which was absent in livers of fasted animals. UT-1 cells stimulated to overexpress HMG-CoA reductase mRNA were strongly positive with the same probe. Control hybridizations with sense strand RNA probe, or with cRNA probe on pre-RNased tissue were negative. Strong hybridization signal for HMG-CoA reductase mRNA was observed in all tissues of the post-implantation rat embryo, from egg cylinder to 30 somite stages (7 to 12 days). Heavy signal was noted in primitive ectoderm and neural tube. The wide embryonic and extraembryonic distribution and abundance of HMG-CoA reductase mRNA may reflect developmental requirements for products of the mevalonate pathway, e.g., isoprenoids for post-translational farnesylation of p21ras. PMID- 8446928 TI - Additional endpoints and overview of a mouse skeletal variant assay for detecting exposure to teratogens. AB - CD-1 mice were exposed in utero to one of 14 treatment regimes, several of them being replicated, with close agreement between series. Prenatal exposure to a teratogenic dose at a sensitive time enabled detection of 10 of 14 teratogen regimes by alterations in frequency or severity of a substantial number of the 88 variants in the Skeletal Variant Assay System (SVAS) screen when examined at 60 65 days post natal (DPN). These included 2,4,5-T (245T), Trifluralin (TFL), Maneb (MNB), Decamethrin (DMT), Acetazolamide (ACZM) either at 8 days post-coitus (DPC) or days 9-11 PC, trypan blue (TB), or 5' Bromodeoxyuridine (BUDR) on either 7 DPC, 8 DPC, or 9 DPC. Most of these observations have been reported elsewhere. All of the treatment regimes mentioned above, and another group of treatments, could be detected in the exposed CD-1 cohorts when additional endpoints were employed. One such endpoint was "frequently responding variants." These were: Interfrontals (IF), Parted Frontals (PF), Preoptic Sutures (PS), Foramina Transversaria Imperfecta of the first cervical (C) vertebra (FTI C1), FTI of the axis (C2), Accessory (Acc) Transverse Foramina (TF) of C3-C6, malformations of C3 C7, Fourteen (14) Ribs, Carpal Fusions (Fus), Lumbar Fus, 27-Presacral Vertebrae (PSV), and Sacral Fus. This endpoint revealed significant differences in the initial group of 10, plus Captan (CAPT) and Phenytoin (DPH). Yet another useful endpoint reported here was the existence of high magnitude effects (i.e., dramatic alterations in frequency of occurrence of a variant). These included IF in TB and ACZM; PF in ACZM; PS in BUDR; FTI-C1 in TB and 245T; FTI-C2 in 245T; 14 Ribs in ACZM, BUDR, and TFL; Carpal Fus in TB; 27-PSV in ACZM; Fewer than (<) 30 Caudal Vertebrae (Vert) in 245T, TFL; Caudal Fus in TB, ACZM-D9. Eight treatment regimes in all could be detected by the existence of 3 or more high magnitude effects (245T, MNB, TB, ACZM8, ACZM9-11, phenytoin, and possibly BUDR on days 7 or 8, each seen in one of two series only). Clusters of related variants were affected in 9 of the 14 groups: Frontal (F) bones and C Vert in 245T; F bones in ACZM-D8; Fus in Posterior Vert Column in ACZM-D9-11; C Vert and Fus in Vert and articular skeleton in TB; Thoracic (Th) Vert and rib-cage effects in BUDR.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8446929 TI - Evaluation of the bioeffects of prenatal ultrasound exposure in the cynomolgus macaque (Macaca fascicularis): III. Developmental and hematologic studies. AB - The multiple applications of diagnostic ultrasound in obstetrics have resulted in a continued rise in the prenatal population exposed each year. Although human epidemiologic and experimental studies with various animal models have not consistently documented any significant, reproducible findings related to clinically relevant exposures, technologic changes in scanning equipment and gaps in our knowledge regarding the interaction(s) of ultrasound with tissues emphasize the need to pursue safety issues. Studies with nonhuman primates have provided information on the potential for pre and postnatal effects on offspring exposed repeatedly during gestation (ATL MK 600, 7.5 MHz, ISPTA = 27 mW/cm2; ISPPA = 85 W/cm2; Estimated power = 12 mW--scanned for 10 min 5 times weekly gestational day [GD] 20-35; 3 times weekly GD 36-60; once weekly for 20 min GD 60 150). These studies have indicated transient effects on body weight, white blood cell counts (WBCs), and muscle tone postnatally. In an effort to confirm these findings and focus on hematologic changes, a second series of studies was initiated using the same exposure conditions (N = 22; 11 exposed, 11 sham controls). Data derived from both studies were combined and confirmed transient reductions in body weights for infants up through 4 months of age (P < or = 0.03); no statistically significant differences in muscle tone were noted. Similar to the original findings, WBCs were transiently reduced on days 3 (P < or = 0.02) and 21 (P < or = 0.05); prenatal sampling indicated a significant difference between the groups on GD 140 (P < or = 0.04). No direct effects were evident in bone marrow aspirates collected on postnatal days 3, 9, and 21 +/- 1. Although animals were able to compensate for these observed changes and remained unaffected by their occurrence, additional studies will be required to further our understanding of this phenomenon. PMID- 8446930 TI - Morphology of the cardiovascular system in conjoined twins: spatial and sequential segmental arrangements in 36 cases. AB - Thirty-six pairs of conjoined twins are reviewed from the joint experience of the authors. The external forms of conjunctions were 18 thoracopagus (joined at chest), eight cephalothoracopagus (joined at head and chest), eight dicephalus (single trunk and two heads), one craniopagus (joined at head), and one omphalopagus (joined at abdomen). There was one case with a single conventional heart in association with isomerism of the left lungs and absence of the heart in the left-side twin. Six cases had two conventional hearts. All of them had associated lesions, which were more severe in three cases (50%) with abnormal laterality. All of the cephalothoracopagus (eight cases) had two shared hearts. Cardiac lesions were commonly seen in the posterior heart, but the arrangement of atrial appendages were normal in every heart. Twenty-one cases of either dicephalus or thoracopagus had a compound heart. Three cases (14%) had fusion only at the level of venous sinus; three others (14%) were fused at the atrial level only, but 15 cases (71%) had fusion at both atrial and ventricular levels. Abnormal laterality was an associated lesion in ten cases (48%) with a compound heart. The fusion at the atrial level always occurred between right atriums, but ventricular fusion was more commonly between two left ventricles. Four atrial or ventricular chambers, if fused, were arranged in a cruciate arrangement. Mode of conjunction was as important, in the formation of the cardiovascular system, as was the degree of fusion. Abnormal laterality, which is commonly associated in lateral or mixed lateral/facing conjunction, was the most important factor affecting the general morphology of the cardiovascular system. PMID- 8446931 TI - Evidence of a hypercoagulable state in patients with acute lymphoblastic leukemia treated with low dose of E. coli L-asparaginase: a GIMEMA study. AB - Blood coagulation abnormalities induced by administration of E. coli L asparaginase were investigated in 25 patients with acute lymphoblastic leukemia treated according to the GIMEMA ALL 0288 trial. Dosage of L-asparaginase was relatively low (6,000 U/m2/day for 7 days total dose 42,000 U/m2) as compared to the conventional dosages (120,000-140,000 U/m2 over 10-14 days). A significant decrease in fibronogen, plasminogen, alpha2-antiplasmin and antithrombin III was observed from day IV of L-asparaginase and it was maximum on day VIII, with return to the baseline levels on day XV. Protein C levels had only a borderline reduction, while no modification of protein S or factor VII was observed. Two of the patients investigated developed thrombosis. The presence of a prothrombotic state induced even by this low dosage of E. coli L-asparaginase was suggested by a significant increase of sensitive markers of hypercoagulability such as fibrinopeptide A, thrombin-antithrombin complexes, and prothrombin fragment F1 + 2. PMID- 8446932 TI - 125I-fibrinogen leg scanning: reassessment of its role for the diagnosis of venous thrombosis in post-operative patients. AB - OBJECTIVE: To determine the reasons why 125I-fibrinogen leg scanning, a screening test which was reported to be very sensitive for the detection of post-operative thrombosis, has shown poor sensitivity in contemporary studies. STUDY IDENTIFICATION: English-language reports were identified through a Medline computer search (1965-1991), Current Contents, and an extensive manual search of the bibliographies in identified articles. STUDY SELECTION: Studies in orthopaedic or general surgical patients were reviewed that compared 125I fibrinogen leg scanning with venography in all patients (accuracy studies) or in patients in whom 125I-fibrinogen leg scanning became positive (positive predictive value studies). DATA EXTRACTION: A systematic appraisal of study design and specific descriptive information concerning the selection of patients. RESULTS OF DATA SYNTHESIS: Six of the 15 studies which compared 125I-fibrinogen leg scanning with venography were level 1 studies (potential for bias minimized) and nine were classified as level 2 studies (potential for bias not minimized). In orthopaedic surgical patients, the pooled sensitivity of leg scanning for isolated calf vein thrombosis, for all venous thrombosis, and the pooled specificity were 55%, 45%, and 92% for the level 1 studies, respectively. These indices were 88%, 82%, and 79%, respectively for the level 2 studies (P < 0.001). Only two (level 2) studies were found that evaluated the accuracy of leg scanning for venous thrombosis in general surgical patients. CONCLUSION: We conclude that leg scanning is an insensitive method for the screening of post-operative venous thrombosis in orthopaedic patients. Our findings call into question the validity of the many studies (including meta-analyses) evaluating prophylactic agents for venous thrombosis which used leg scanning as the only test for the assessment of efficacy. PMID- 8446933 TI - The development of homologous (canine/anti-canine) antibodies in dogs with haemophilia A (factor VIII deficiency): a ten-year longitudinal study. AB - The development of inhibitors to factor VIII in patients with haemophilia A remains as a serious complication of replacement therapy. An apparently analogous condition has been described in a canine model of haemophilia A (Giles et al., Blood 1984; 63: 451). These animals and their relatives have now been followed for 10 years. The observation that the propensity for inhibitor development was not related to the ancestral factor VIII gene has been confirmed by the demonstration of vertical transmission through three generations of the segment of the family related to a normal (non-carrier) female that was introduced for breeding purposes. Haemophilic animals unrelated to this animal have not developed functionally significant factor VIII inhibitors despite intensive factor VIII replacement. Two animals have shown occasional laboratory evidence of factor VIII inhibition but this has not been translated into clinical significant inhibition in vivo as assessed by clinical response and F.VIII recovery and survival characteristics. Substantial heterogeneity of inhibitor expression both in vitro and in vivo has been observed between animals and in individual animals over time. Spontaneous loss of inhibitors has been observed without any therapies designed to induce tolerance, etc., being instituted. There is also phenotypic evidence of polyclonality of the immune response with variable expression over time in a given animal. These observations may have relevance to the human condition both in determining the pathogenetic factors involved in this condition and in highlighting the heterogeneity of its expression which suggests the need for caution in the interpretation of the outcome of interventions designed to modulate inhibitor activity. PMID- 8446934 TI - Intravascular coagulation in liver transplantation--is it present or not? A comparison between orthotopic and heterotopic liver transplantation. AB - It is still not clear whether disseminated intravascular coagulation (DIC) contributes to the hemostatic disturbances in orthotopic liver transplantation (OLT). Theoretically the lack of hepatic clearance of procoagulant factors during the anhepatic period and the release of thromboplastic material from the graft might trigger DIC. During heterotopic liver transplantation (HLT) the host liver is left in situ and procoagulant factors may still be cleared; DIC, if present, may not occur until after reperfusion. The aim of the present study was to gain more insight into the underlying mechanism of the coagulation changes during liver transplantation by comparison of OLT and HLT. Thrombin-antithrombin-III complexes (TAT), and indicator of thrombin generation, fibrin degradation products (FbDP) and routine clotting times were assayed in 12 OLTs, 18 HLTs and in a control group of 10 partial hepatic resections (PHR). TAT increased dramatically after reperfusion to 136 micrograms/l in OLT and to 94 micrograms/l in HLT (p n.s.). In contrast, FbDP levels increased only in OLT, to a maximum of 13.8 micrograms/ml. Routine clotting times changed mildly and similarly in both OLT and HLT. CONCLUSIONS: Graft reperfusion triggers excessive thrombin formation, but there are no other signs of subsequent DIC. Any thrombin formed is probably rapidly inhibited by antithrombin-III. The rise in FbDP during OLT is the result of increased fibrinolysis, which occurred only in OLT and not in HLT. PMID- 8446935 TI - Pentasaccharide and Orgaran arrest, whereas heparin delays thrombus formation in a rat arteriovenous shunt. AB - The mode of action of glycosaminoglycans (GAGs) towards thrombus formation in a rat arteriovenous shunt was studied by simultaneous examination of thrombus weight, platelet consumption and thrombin generation during 45 min of blood circulation. A comparison was made between the effects of heparin, the heparinoid Org 10172 (Orgaran), and the chemically synthesized methoxy derivative of the antithrombin III binding pentasaccharide fragment of heparin (Org 31540). All three compounds inhibited thrombus growth by 30% at a dose of 80 anti-Xa U/kg i. v. when assessed after 15 min of circulation through the shunt. In addition, a systemic decrease of 27% of platelet numbers in the placebo group was inhibited by heparin and Orgaran with 63% and by pentasaccharide with 48%. At a later stage, after 45 min of circulation, at comparable plasma anti-Xa levels, thrombi which had formed in the presence of Orgaran or pentasaccharide, but not in the presence of heparin, became less or non thrombogenic. This non-thrombogenicity was reflected by i) an inhibition of the local deposition of [51Cr]platelets of 75% with Orgaran and of 57% with pentasaccharide, and ii) an inhibition of ex vivo thrombus-induced thrombin generation in pooled rat plasma of 67% with Orgaran and of 52% with pentasaccharide (inhibition compared to placebo). Although the mechanism of inducing non-thrombogenicity of a (developing) thrombus by Orgaran and pentasaccharide requires further investigation, the suppression of the local thrombin generation potency, measured by thrombus-induced thrombin generation in pooled plasma, is much more correlated with thrombus growth than systemic anticoagulant activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446936 TI - Multi-center study of thromboplastin calibration precision--influence of reagent species, composition, and International Sensitivity Index (ISI). AB - Four thromboplastin reagents were tested by 18 laboratories in Europe, North America, and Australasia, according to a detailed protocol. One thromboplastin was the International Reference Preparation for ox brain thromboplastin combined with adsorbed bovine plasma (coded OBT/79), and the second was a certified reference material for rabbit brain thromboplastin, plain (coded CRM 149R). The other two thromboplastin reagents were another rabbit plain brain thromboplastin (RP) with a lower ISI than CRM 149R and a rabbit brain thromboplastin combined with adsorbed bovine plasma (RC). Calibration of the latter two reagents was performed according to methods recommended by the World Health Organization (W.H.O.). The purpose of this study was to answer the following questions: 1) Is the calibration of the RC reagent more precise against the bovine/combined (OBT/79) than against the rabbit/plain reagent (CRM 149R)? 2) Is the precision of calibration influenced by the magnitude of the International Sensitivity Index (ISI)? The lowest inter-laboratory variation of ISI was observed in the calibration of the rabbit/plain reagent (RP) against the other rabbit/plain reagent (CRM 149R) (CV 1.6%). The highest inter-laboratory variation was obtained in the calibration of rabbit/plain (RP) against bovine/combined (OBT/79) (CV 5.1%). In the calibration of the rabbit/combined (RC) reagent, there was no difference in precision between OBT/79 (CV 4.3%) and CRM 149R (CV 4.2%). Furthermore, there was no significant difference in the precision of the ISI of RC obtained with CRM 149R (ISI = 1.343) and the rabbit/plain (RP) reagent with ISI = 1.14. In conclusion, the calibration of RC could be performed with similar precision with either OBT/79 or CRM 149R, or RP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446937 TI - Effect of heparin on thrombin inhibition in the microcirculation. AB - Disappearance of thrombin enzymatic activity was measured during recirculation through the microvasculature in a rat Langendorff heart preparation. This resulted in a 50% loss of thrombin from the recirculating solution. No increased loss of thrombin could be demonstrated if a mixture of antithrombin III and thrombin was recirculated, compared to thrombin alone. If, however, a heparin/thrombin mixture was recirculated, a 90% loss of thrombin could be demonstrated. Pretreating the microvasculature with large amounts of heparin resulted in recovery of antithrombin III in the recirculated heparin solution. At a subsequent recirculation with a heparin/thrombin mixture the loss of thrombin was decreased to the control level, as seen when recirculation with thrombin alone was performed. It is concluded that disappearance of thrombin enzymatic activity from a solution when recirculated through the microcirculation can be considerably increased if recirculated together with heparin, which probably reacts with endogenous antithrombin III on the vessel wall. The disappearance of thrombin in the absence of heparin was, however, unaffected by antithrombin III. The latter finding is compatible with the hypothesis that, in the microcirculation, antithrombin III/glycosaminoglycans play only a minor role for inhibition of thrombin coagulant activity and that thrombin binds mainly to thrombomodulin. PMID- 8446938 TI - Influence of cardiac output on peak t-PA plasma levels in patients receiving thrombolytic therapy with recombinant tissue-type plasminogen activator- correlation with patency rate. AB - We studied 35 consecutive patients with short onset of myocardial infarction who underwent thrombolytic therapy with rt-PA at a standard dosage regimen of 100 mg rt-PA total (10 mg given as a bolus followed by 50 mg, 20 mg and 20 mg per hour for 3 hours). These patients were monitored for t-PA antigen and t-PA activity and PAI-1 activity plasma levels during rt-PA infusion. Success or failure of thrombolytic therapy was evaluated by non-invasive criteria (early plasma creatine kinase peaks, early peak plasma myoglobin values, and electrocardiographic criteria) as well as by means of coronary angiography at the fourth day after thrombolytic treatment. In 24 (68.6%) of these patients a success of thrombolytic therapy could be established by these criteria, while 11 patients did not respond to thrombolytic therapy. Fifteen patients (14 responders and one non-responder) had to be excluded from the further evaluation because in these patients clinical laboratory data obtained upon admission before initiation of thrombolytic therapy were not complete. Therefore, 20 patients (10 responders and 10 non-responders) could further be analysed. The two groups of patients were not significantly different in body weight, body weight index, age, gender, liver or kidney functional parameters as determined before initiation of the thrombolytic therapy. Furthermore, PAI-1 plasma levels before initiation of thrombolytic therapy were not significantly different in the two groups, as were rt-PA dosage per body weight or body weight index.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446939 TI - Evolution of urokinase-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA) in orthotopic liver transplantation (OLT). AB - In orthotopic liver transplantation (OLT) hyperfibrinolysis seems to be of causative importance for intra- and postoperative bleeding. Although recently hyperfibrinolysis has been successfully reduced by intraoperative aprotinin treatment, small increases of fibrinolysis still remain during OLT. Originally, tissue-type plasminogen activator (t-PA) was considered to be responsible for the increases, but the efficacy of aprotinin which inhibits besides plasmin also kallikrein and urokinase-type plasminogen activator (u-PA) suggested also a role for the intrinsic and contact system-dependent plasminogen activators. We investigated the role of u-PA. From 29 patients undergoing OLT with intraoperative aprotinin infusion arterial blood samples were taken at 7 different time points. The preoperative median values for u-PA antigen (u-PA Ag) and plasmin-activatable single-chain u-PA (scu-PA) levels, which were more than 2 fold above normal (both: p < 0.01), decreased slightly during the preanhepatic phase and remained unchanged during the anhepatic phase. With reperfusion of the graft liver the two levels decreased significantly (p = 0.0003 and p = 0.006, respectively) to almost normal values, probably due to clearance by the graft liver. Active two-chain u-PA (tcu-PA) was preoperatively 2-fold above the detection limit, remained stable during the preanhepatic phase and increased 2 fold in the anhepatic phase (p = 0.0018). As expected tcu-PA also relapsed upon reperfusion, but to the preoperatively enhanced level, possibly caused by sustained activation of scu-PA by cathepsin B. t-PA activity levels were at the upper end of the normal range preoperatively, slightly increased during preanhepatic and anhepatic phases and decreased significantly with reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8446940 TI - Protein C deficiency: a database of mutations. For the Protein C & S Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. PMID- 8446941 TI - Investigations into the clinical utility of latex D-dimer in the diagnosis of deep venous thrombosis. AB - The serial use of non-invasive tests has been shown to be a safe method of managing outpatients who are suspected of having lower limb deep venous thrombosis (DVT). Objective testing has shown that the majority of these outpatients do not have venous thrombosis. A rapid test to exclude DVT in these patients, without the need for expensive and inconvenient serial noninvasive vascular testing, would have practical and economic advantages. Studies measuring the fibrin degradation product D-dimer using enzyme-linked immunoassays (EIA) in patients with venographically proven DVT suggest that it should be possible to exclude this condition by the use of one of the rapid latex bead D-dimer tests. We have examined 190 patients with suspected DVT using both a latex and an EIA D dimer assay. The latex D-dimer test used in this study was negative in 7 of the 36 proven cases of DVT. This sensitivity of only 80% is not sufficient to allow this type of assay, in its current form, to be used as an exclusion test for DVT. The same plasma samples were tested with an EIA assay. This information was used to mathematically model the effects of selecting a range of D-dimer discriminant cut off points for the diagnosis of DVT. These results indicate that 62% of suspected clinically significant DVT could have this diagnosis excluded, with a 98% sensitivity, if the rapid latex or equivalent D-dimer test could be reformulated to measure less than 185 ng/ml of D-dimer. PMID- 8446942 TI - Status of present and candidate international reference preparations (IRP) of thromboplastin for the prothrombin time. A report of the Subcommittee for Control of Anticoagulation. PMID- 8446943 TI - C4b-binding protein: an update. PMID- 8446944 TI - A note on the calculation of recovery for factor VIII infusions. PMID- 8446945 TI - Thrombin generation in thrombotic thrombocytopenic purpura--reply. PMID- 8446946 TI - Endocytosis of monoclonal anti-glycoprotein IIb/IIIa antibody in unstimulated platelets. PMID- 8446947 TI - Venous occlusion does not release von Willebrand factor, factor VIII or PAI-1 from endothelial cells--the importance of consensus on the use of correction factors for haemoconcentration. PMID- 8446948 TI - Contact activation, heparins and cardiopulmonary bypass. PMID- 8446949 TI - In memoriam Arthur Leslie Bloom 1930-1992. PMID- 8446950 TI - Platelet adhesion at low shear rate: study of a normal population. AB - The use of oral contraceptives (OCs) has been associated with vascular complications. The mechanism(s) by which OCs predispose to thrombotic events remains unclear. Recent studies have demonstrated that postmenopausal (PM) women who take estrogen replacement therapy (ERT) have a decreased incidence of myocardial infarction compared to those who do not take ERT. This study was undertaken to determine if healthy individuals have differences in platelet adhesion depending on hormonal status. Men, PM women taking ERT, PM women not taking ERT, OC users, and premenopausal women not taking any medications were studied. Platelet studies were performed in a Hele-Shaw flow chamber at a low shear rate using platelet-rich plasma. The platelet adhesion process to subendothelial components: fibronectin, collagen I and collagen III was recorded using a 35 mm camera mounted on an inverted microscope. Photographs were taken at 30 second intervals for a total of 12 minutes and analyzed using a modified computer program which provided a numerical account of platelet adhesion. OC users had significantly higher platelet adherence to fibronectin, collagen I and collagen III compared to all other groups. All other study groups had similar platelet adhesion independent of hormonal status. These findings suggest that OCs cause increased platelet adhesion in some individuals and this may be one of the mechanisms by which OCs contribute to thrombotic events. PMID- 8446951 TI - Characterization of platelet hypofunctions in rats under SART stress (repeated cold stress). AB - Platelet hypoaggregability has been reported in rats exposed to a chronic form of environmental stress induced by long-lasting fluctuation in air temperature, known as SART (specific alternation of rhythm in temperature) stress. This study examines functional characteristics of platelets from stressed rats in more detail. Exposure to stress reduced aggregation and ATP release in platelets stimulated with collagen, as determined using platelet-rich plasma (PRP). The resting levels of ATP but not ADP in platelets from stressed rats were lower than those from unstressed ones. Collagen-induced release and resting level of serotonin also decreased in platelets from stressed rats. In contrast, stress failed to cause hypoaggregability of washed platelets. Circulating platelet aggregates were detected in stressed rats. From these data, SART stress appears to cause intravascular activation of platelets in spite of in vitro hypofunctions. Alteration in plasma milieu may be associated with stress-induced platelet hypofunctions in PRP. PMID- 8446952 TI - High-level expression of antibody-plasminogen activator fusion proteins in hybridoma cells. AB - We show that the mouse gamma 2b heavy chain or human beta-globin 3' untranslated region can greatly enhance protein expression in myeloma cells transfected by genes coding for antibody-plasminogen activator fusion proteins. Expression plasmids were constructed containing a cloned genomic heavy chain variable region from fibrin-specific monoclonal antibody 59D8, a cloned genomic constant region of the mouse gamma 2b heavy chain, and DNA sequence coding for either tissue-type plasminogen activator (tPA) or a segment of urokinase (UK) and their respective 3' untranslated sequences. Cell lines transfected with these constructs, pSVtPA (tPA) and pSVUKG(UK), produced extremely low levels of mRNA and protein (0.008 0.06 micrograms/ml) in comparison with the parental 59D8 myeloma cell line (7.6 10 micrograms/ml). In vitro nuclear run-off analysis indicated that the low steady-state levels of mRNA encoded by pSVUKG(UK) did not result from a lower rate of transcription of the transfected gene (relative to the rate of transcription of the endogenous heavy chain gene in the 59D8 parent cells). In an attempt to increase protein secretion, we assembled the expression plasmids pSVtPA(Ig), pSVUKG(Ig), and pSVUKG(beta), in which the 3' untranslated region of the mouse gamma 2b heavy chain or human beta-globin gene was substituted for the 3' untranslated region of the plasminogen activator gene. Analysis of supernatant media from cell lines transfected with these constructs showed an increase in recombinant protein secretion of 68 to 100 fold in comparison with that from cell lines transfected with pSVtPA(tPA) or pSVUKG(UK). PMID- 8446953 TI - A quantitative, semi-automated and computer-assisted test for lupus anticoagulant. AB - We describe the design of a quantitative test for lupus anticoagulants (LA), based on the Activated Partial Thromboplastin Time (APTT) and the Russell Viper Venom Time (RVVT). In this assay system, test plasmas mixed 1:1 with a pooled normal plasma (NP) are tested at a low as well as a high cephalin concentration, using an ACL 3000 automated clot timer. The ratio of these two clotting times, divided by the corresponding ratio for the NP, was defined as the Lupus Ratio (LR) and calculated by means of a computer program. The frequency distribution of the LR in a reference population of 150 healthy individuals was determined, and the 97.5 percentile was defined as the upper reference limit and allocated the value one Lupus Anticoagulant Unit (LA-U). Using dilutions of one strong LA positive plasma, standard curves for LA-U determination were constructed for the APTT as well as the RVVT based test, and fitted with a log-logit computer model. The sensitivity of the tests was comparable to that of the Kaolin Clotting Time (KCT). Plasma samples from warfarin treated patients were uniformly negative, while most heparin-containing plasmas were positive in both tests. Plasmas deficient in Factors V, VIII and IX were negative, whereas one Factor VIII inhibitor containing plasma was positive in the APTT and negative in the RVVT. The present work shows that it is possible to adapt the APPT as well as the RVVT for LA quantification. With an automated clot timer and computer based calculation of results, the assays are simple and reproducible and have a high sensitivity and specificity. PMID- 8446954 TI - The effect of ultrasonic irradiation and temperature on fibrinolytic activity in vitro. PMID- 8446955 TI - [Cesarean section in cattle: always act sensibly]. AB - The autopsies of 11 cows, that died after a caesarean section, are described. In a number of cases the operation had performed without the requisite professional skill and care. The opinions of 54 practising veterinarians who responded to an anonymous questionnaire about the operations are described. PMID- 8446956 TI - [Current viewpoints in mechanisms of bone length growth]. AB - Pertinent morphology and physiology of the growth plate is discussed and theories related to mechanisms of bone length growth are reviewed. PMID- 8446957 TI - [Evaluation of histological studies of brains in pigs]. AB - The aim of this study was to formulate guidelines to determine whether, on the basis of the anamnesis, the age of the animal at slaughter, and the post-mortem findings, histological examination of the brain is necessary to arrive at a reliable diagnosis. In total 3159 animals were examined at the laboratory of the Animal Health Service in Gouda over the period from 1 August 1988 to 1 August 1990. Histological examination is recommended for pigs that show nervous signs, motor disturbances, and poor appetite without a clear cause of death, and for fattening pigs in which the post-mortem examination fails to detect abnormalities severe enough to cause death. Histological examination is also recommended when the animal has an overfilled stomach and/or a hard colon content. The examination is not necessary for pigs with intestinal disturbances or for pigs with endocarditis, polyserositis, or visible abnormalities of the brain. The occurrence of meningitis and encephalitis add little to the diagnosis. PMID- 8446958 TI - [Skin problems, edema and diarrhea in a yearling stallion. Symptoms of a cecum-in colon invagination?]. AB - A Dutch Warmblood yearling stallion was referred for skin lesions, oedema and diarrhoea. At rectal palpation a cecocolonic intussusception was diagnosed, that might have been present for at least one week. A short literature review of cecocolonic intussusception is given. PMID- 8446959 TI - Identification of the site at which phospholipase A2 neurotoxins localize to produce their neuromuscular blocking effects. AB - Experiments were conducted on mouse hemidiaphragm preparations using five phospholipase A2 neurotoxins of differing chain structures and antigenicities [notexin (one chain); crotoxin (two chains not covalently bound), beta bungarotoxin (two chains covalently bound); taipoxin (three chains), and textilotoxin (five chains; one copy each of three chains and two copies of a fourth chain)]. Three clostridial neurotoxins (botulinum neurotoxin types A and B, and tetanus toxin) were used in comparison experiments. Phospholipase A2 neurotoxins produced concentration-dependent blockade of neuromuscular transmission. There was no obvious relationship between chain structure and potency, but there was an indication of a relationship between chain structure and binding. The binding of notexin was substantially reversible, the binding of crotoxin was slightly reversible, and the binding of beta-bungarotoxin, taipoxin and textilotoxin was poorly reversible. Experiments with neutralizing antibodies indicated that phospholipase A2 neurotoxins became associated with binding sites on or near the cell surface. This binding did not produce neuromuscular blockade. When exposed to physiological temperatures and nerve stimulation, bound toxin disappeared from accessibility to neutralizing antibody. This finding suggests that there was some form of molecular rearrangement. The two most likely possibilities are: (1) there was a change in the conformation of the toxin molecule, or (2) there was a change in the relationship between the toxin and the membrane. The molecular rearrangement step did not produce neuromuscular blockade. At a later time there was onset of paralysis; the amount of time necessary for onset of blockade was a function of toxin concentration. Phospholipase A2 neurotoxins were not antagonized by drugs that inhibit receptor mediated endocytosis. In addition, phospholipase A2 neurotoxins did not display the pH-induced conformational changes that are typical of other endocytosed proteins, such as clostridial neurotoxins. However, phospholipase A2 neurotoxins were antagonized by strontium, and this antagonism was expressed against toxins that were free in solution and toxins that were bound to the cell surface. Limited antagonism was expressed after toxins had undergone molecular rearrangement, and no antagonism was expressed after toxin-induced neuromuscular blockade. The cumulative data suggest that phospholipase A2 neurotoxins are not internalized to produce their poisoning effects. These toxins appear to act on the plasma membrane, and this is the site at which they initiate the events that culminate in neuromuscular blockade. PMID- 8446960 TI - Immunosuppressive effects of Pseudomonas aeruginosa exotoxin A on human B lymphocytes. AB - In this study we investigated the effects of exotoxin A on proliferation and differentiation of human B-cells in vitro. Exotoxin A at a concentration of 1 microgram/ml inhibited the proliferation of B-cells preactivated by insolubilized anti-IgM antibody or by formalinized Staphylococcus aureus particles, plus IL-2 or IL-4. B-cell blasts obtained after preactivation of tonsillar B-cells produce IgG and IgM in culture supernatants, and this Ig production is enhanced by IL-2 or IL-4. Exotoxin A inhibited the production of IgG and IgM by the B-blasts at the concentration of 1 microgram/ml. PMID- 8446961 TI - Purification and amino acid sequences of six Tx3 type neurotoxins from the venom of the Brazilian 'armed' spider Phoneutria nigriventer (Keys). AB - Six neurotoxic peptides (Tx3-1 to Tx3-6) were purified from the venom of the spider Phoneutria nigriventer by a combination of gel filtration, reverse phase FPLC on PEP-RPC and PRO-RPC columns, reverse phase HPLC on Vydac C18, and ion exchange HPLC on cationic and anionic columns. These toxins caused different neurological symptoms in mice after intracerebroventricular injection. At dose levels of 5 micrograms/mouse, Tx3-3 and Tx3-4 caused rapid general flaccid paralysis followed by death in 10-30 min; Tx3-2 induced immediate clockwise gyration and flaccid paralysis after 6 hr; Tx3-1, Tx3-5 and Tx3-6 produced paralysis only in the posterior limbs and gradual decreases in movement and aggression during 24 hr. The mol. wt of these cystine-rich peptides were found to be in the range of 3500-8500 by mass spectroscopy and SDS-PAGE. The complete amino acid sequences of the neurotoxins Tx3-1 (40 residues), Tx3-2 (34 residues) and Tx3-6 (55 residues), and the N-terminal sequences of Tx3-3 (34 res.), Tx3-4 (40 res.) and Tx3-5 (36 res.) were established by direct automated Edman degradation, and manual DABITC/PITC microsequence analyses of peptides obtained from digests with various proteases. The structures of these Tx3 neurotoxins from Phoneutria nigriventer exhibited sequence similarities to one another and to the neurotoxins from the venoms of the spiders Hololena curta and Agelenopsis aperta, which were most evident in the location of the Cys residues. PMID- 8446962 TI - Species difference in modulation of calcium release by Naja naja kaouthia snake venom cardiotoxin in terminal cisternae from human and equine skeletal muscle. AB - The modulation of Ca2+ release by a cardiotoxin (CTX) from Naja naja kaouthia snake venom was examined in terminal cisternae-containing fractions from equine and human skeletal muscle. Pretreatment with CTX (10 microM) decreased by 27% (human muscle), or had no effect on (equine muscle), the threshold of Ca(2+) induced Ca2+ release. If terminal cisternae fractions were first preloaded with Ca2+ to greater than 65% of the threshold of Ca(2+)-induced Ca2+ release and then CTX added, an immediate and sustained release of Ca2+ occurred in preparations from both species. Addition of CTX after a Ca2+ preload of less than 60% of the threshold of Ca(2+)-induced Ca2+ release did not elicit Ca2+ release in preparations from either species. Ruthenium red (10 microM) antagonized CTX induced Ca2+ release, whereas dantrolene (10 microM) did not. These findings suggest that the effects of CTX on the Ca2+ release channel are dependent on Ca2+ preload and that CTX may be an important probe of the Ca(2+)-modulated Ca2+ release process and in understanding regulation of Ca2+ release in skeletal muscle from different species. PMID- 8446963 TI - Molecular cloning of a cardiotoxin structural gene from Malayan spitting cobra (Naja naja sputatrix). AB - The structural gene and cDNA encoding cardiotoxin in Naja naja sputatrix have been cloned and characterized with a view to study the gene protein relationships and also to produce pure protein in large amounts. Using the polymerase chain reaction on the total RNA isolated from the venom glands, the structural gene (180 bp) has been synthesized and expressed in Escherichia coli to produce a fusion protein with beta-galactosidase. Immunoblotting using polyclonal antibodies raised against the total venom in rabbits demonstrated the presence of cross-reacting proteins in plaques produced by recombinant lambda gt11 phages. PMID- 8446964 TI - Turbidity of hyperimmune equine antivenom: the role of phenol and serum lipoproteins. AB - Twenty batches of polyvalent antivenom produced at the Instituto Clodomiro Picado were analyzed for turbidity, both before and after freezing-thawing and lyophilization. Eight batches became turbid upon freezing-thawing, and this change correlated with high levels of cholesterol, triglycerides and lipoproteins, especially beta-lipoprotein. Since normal horse serum does not become turbid after freezing-thawing, despite the fact that it has high lipoprotein levels, the possibility was raised that phenol, used as a preservative during serum fractionation, might affect lipoproteins, inducing the appearance of turbidity after freezing-thawing. This hypothesis was tested by fractionating a sample of hyperimmune serum either without phenol or using two different phenol concentrations (0.1 g/dl and 0.25 g/dl). Results showed that, although the three samples had the same cholesterol and triglyceride levels before fractionation, only the one having 0.25 g/dl phenol became turbid upon freezing-thawing, containing a diffuse lipoprotein band on electrophoresis. This finding suggests that turbidity in equine antivenoms depends on the interaction of at least three factors: (a) freezing, (b) high initial cholesterol and lipoprotein concentration in the serum, and (c) addition of phenol during fractionation of serum. PMID- 8446965 TI - Inhibition of calcium-dependent contractions of the isolated guinea-pig ileal longitudinal muscle and taenia coli by the total glycosidic extract of the plant Sarcolobus globosus. AB - The effect of the total glysosidic extract of the plant Sarcolobus globosus was investigated on the contractions of the smooth muscle of the guinea-pig ileal longitudinal muscle and taenia coli. In the ileal longitudinal muscle, addition of the extract inhibited the electrical field-stimulated twitches. Similarly to verapamil, it also reduced the contractions of the muscle to acetylcholine, histamine and KCl. However, only the tonic contraction to KCl was reversed by increasing the extracellular calcium concentration. In the taenia coli, lower concentrations of both the extract and verapamil induced a parallel displacement of the dose-response curves to calcium (0.30-30 mM). Addition of the extract also dose-dependently inhibited the KCl-induced contraction of the taenia coli. Increasing the calcium concentration increased the IC50 values of the extract. The result suggests that the inhibitory effect of the Sarcolobus globosus extract on the smooth muscle, like verapamil, is mainly due to inhibition of calcium influx. PMID- 8446966 TI - Effects of enhancer mutations on the expression of human immunodeficiency virus 1 regulated luciferase and diphtheria toxin A chain genes in transfected cells. AB - This study explores human immunodeficiency virus 1 (HIV-1)-regulated diphtheria toxin A (DT-A) gene expression as a means of eradicating HIV-infected cells. Previously, we constructed luciferase and DT-A plasmids, containing cis-acting Tat and Rev responsive elements, which showed low basal expression and required both Tat and Rev for maximal expression. Cell lines which had stably integrated the DT-A constructs were resistant to HIV production. To reduce toxicity due to basal expression, this study investigates the effect of mutations in the HIV enhancer on expression of luciferase and DT-A plasmids. Some mutations were found to substantially reduce basal expression while still allowing for trans activation. Such mutations, in combination with attenuated versions of DT-A, may make regulated toxin gene expression feasible as a therapy for AIDS. PMID- 8446967 TI - Aspirin response and failure in cerebral infarction. AB - BACKGROUND AND PURPOSE: The purpose of this study was to assess the biological effect of aspirin as measured by the inhibition of platelet aggregation in patients taking aspirin for stroke prevention and in patients with acute stroke. METHODS: We administered increasing doses of aspirin (325, 650, 975, and 1,300 mg daily) to 113 patients for stroke prevention and measured the inhibition of platelet aggregation in these patients and in 33 patients with acute stroke taking aspirin before stroke onset. RESULTS: Eighty-five patients on < or = 325 and six on > or = 650 mg aspirin had complete inhibition of platelet aggregation. Increase of the dose by 325 mg in nine of the 22 patients with partial inhibition of platelet aggregation produced complete inhibition in five patients at 650 mg and in one at 975 mg. At 1,300 mg, three patients still had only partial inhibition of platelet aggregation (aspirin resistance). Of the 33 inpatients with acute stroke, 24 had platelet aggregation studies done before further administration of aspirin. Of these, 19 had complete inhibition of platelet aggregation and three had partial inhibition, with production of complete inhibition of platelet aggregation at dose escalation; one patient was aspirin resistant and the other noncompliant. CONCLUSIONS: How the inhibition of platelet aggregation relates to stroke prevention remains unclear. The ability of aspirin and the dose required to inhibit platelet aggregation may depend upon the individual. PMID- 8446968 TI - Does cerebral infarction after a previous warning occur in the same vascular territory? AB - BACKGROUND AND PURPOSE: The aim of this study was to compare the territory of cerebral infarcts on follow-up with that of the preceding transient ischemic attack or nondisabling stroke. METHODS: The Dutch TIA Trial was a randomized, double-blind, controlled trial, in which the secondary preventive effects of two doses of aspirin were compared in patients with a transient ischemic attack or nondisabling stroke. On the basis of clinical symptoms and computed tomography, qualifying events were classified as pertaining to the left carotid, right carotid, or vertebrobasilar circulation. RESULTS: In 2,993 patients the territory of the qualifying event was that of the left carotid in 1,281 (43%), the right carotid in 1,090 (36%), and the vertebrobasilar in 444 (15%); the territory was uncertain in 178 (6%). On follow-up (mean, 2.6 years), 184 of the 2,371 patients with a baseline event in the carotid circulation suffered a recurrent ischemic stroke (7.8%), as did 28 of the 444 patients in the vertebrobasilar group (6.3%); 117 of these 212 infarcts (55%; 95% confidence interval, 49-62) occurred in the same territory (108 in the ipsilateral carotid and nine in the vertebrobasilar territory) as the event at baseline, compared with 39% to be expected by chance alone (95% confidence interval, 32-45). In the carotid groups patients were significantly more likely to have a subsequent ischemic event in the same territory as at entry than patients in the vertebrobasilar group (relative risk, 1.8; 95% confidence interval, 1.1-3.2). The average interval between the qualifying event and the subsequent stroke was significantly shorter (mean, 167 days; 95% confidence interval, 77-257) if the vascular territory was the same. CONCLUSIONS: These results suggest that single artery disease accounts for at most one half of the strokes on follow-up, relatively more often in the carotid territory, and that recurrent strokes from the same arterial lesion occur sooner than strokes associated with other lesions. PMID- 8446969 TI - Predictors of carotid stenosis in older adults with and without isolated systolic hypertension. AB - BACKGROUND AND PURPOSE: This study was designed to determine the prevalence of carotid stenosis and atherosclerosis in older adults with and without isolated systolic hypertension and to determine risk factors for carotid artery disease in these two groups. METHODS: Duplex scans were performed on 187 participants of the Systolic Hypertension in the Elderly Program and on 187 normotensive control subjects. Doppler measures of blood flow velocity were used to determine the prevalence of internal carotid artery stenosis. RESULTS: Carotid stenosis was found in 25% of hypertensive participants but in only 7% of normotensive participants (p < 0.001). Among hypertensive participants, carotid stenosis was correlated with lower diastolic blood pressure (p = 0.022). In multivariate analysis, systolic blood pressure of > or = 160 mm Hg was the strongest predictor of carotid stenosis. Other variables independently related to stenosis were diastolic blood pressure of < 75 mm Hg (p = 0.001), alcohol use (p = 0.005), heart rate of > or = 80 beats per minute (p = 0.013), smoking (p = 0.034), high concentration of apoprotein B (p = 0.001), and low concentration of high density lipoprotein cholesterol (borderline significant, p = 0.069). Among hypertensive participants, the strongest predictor of carotid stenosis was low diastolic blood pressure. This relation persisted even after taking into account differences in pulse pressure. CONCLUSIONS: Isolated systolic hypertension is strongly correlated with carotid stenosis, and among those with isolated systolic hypertension low diastolic blood pressure is a marker for carotid stenosis. PMID- 8446970 TI - A prospective study of cerebral ischemia in the young. Analysis of pathogenic determinants. The National Research Council Study Group. AB - BACKGROUND AND PURPOSE: The etiology of stroke in the young is different from that in older patients and remains unknown in almost one third of the cases. To gain further insight into both pathogenic and etiologic determinants, we prospectively studied a large number of consecutive young adults with focal cerebral ischemia. METHODS: Three hundred thirty-three patients aged 15-44 years with transient ischemic attack or ischemic stroke within the 8 weeks before hospital admission were recruited and investigated by using a standardized protocol of clinical evaluation, blood tests, electrocardiography, echocardiography, chest roentgenography, and brain computed tomography. Presumed etiology was diagnosed by prospectively applied criteria. RESULTS: Women predominated (61%) among patients under 35 years of age, mainly due to the frequency of cerebral ischemia related to oral contraceptive use, while men outnumbered women (60%) among patients over that age because of a higher prevalence of atherothrombotic disease. Potential cerebral embolism of cardiac origin was the presumed cause of stroke in 23.7%, but conventional sources of emboli were found only in 7.5% of cases. There was a low prevalence of atrial fibrillation among young patients with cerebral ischemia. Mitral valve prolapse was found in 8.4%, as expected, predominantly (71.4%) among the younger patients. The prevalence of stroke over transient ischemic attack was proportional to the likelihood of cardiac embolism. Acute alcohol intoxication was considered a precipitating factor in only three patients. The percentages of cerebral ischemia attributed to arterial dissection (0.3%), oral contraceptive use in women (8.1%), migraine (1.2%), and other associated medical diseases (1.5%) were lower than reported in recent clinical series. CONCLUSIONS: Two different groups of pathogenic determinants predominate in younger women and in older men, supporting public health measures aimed at strict medical control of the recognized cerebrovascular risk factors. PMID- 8446971 TI - Lupus anticoagulant and the fibrinolytic system in young patients with stroke. AB - BACKGROUND AND PURPOSE: Our purpose was to assess the presence of lupus anticoagulant and fibrinolytic system abnormalities in young patients with stroke. METHODS: We studied 33 consecutive ischemic patients aged < 50 years. Lupus anticoagulant was screened by four different coagulation tests, and the fibrinolytic system was studied by analyzing tissue plasminogen activator antigen and plasminogen activator inhibitor activity. RESULTS: Six patients (18%), two of whom were affected by systemic lupus erythematosus, had lupus anticoagulant. Plasminogen activator inhibitor activity was significantly higher in those positive for lupus anticoagulant than in those negative for lupus anticoagulant and control subjects (p < 0.001). CONCLUSIONS: In young patients with stroke, lupus anticoagulant is associated with an imbalance of the fibrinolytic system as a result of higher levels of plasminogen activator inhibitor. PMID- 8446972 TI - Vascular dimensions of the cerebral arteries follow the principle of minimum work. AB - BACKGROUND AND PURPOSE: The principle of minimum work is a parametric optimization model for the growth and adaptation of arterial trees. It establishes a balance between energy dissipation due to frictional resistance of laminar flow (shear stress) and the minimum volume of the vascular system, implying that the radius of the vessel is adjusted to the cube root of the volumetric flow. The purpose of this study is to verify whether the internal carotid artery system obeys the principle of minimum work. METHODS: Measurements of the radius of parent and branch segments of the internal carotid, anterior, and middle cerebral arteries were performed on analog angiographs chosen at random from a set classified as normal. The branch angles were measured from lateral projections in bifurcations of the anterior cerebral artery. The relation of the calibers of parent and branch vessels was analyzed. RESULTS: The area ratio of the bifurcations (N = 174) was 1.2 +/- 0.4 (mean +/- SD). The equation (r0)n = (r1)n + (r2)n was solved for n, resulting in n = 2.9 +/- 0.7 (mean +/- SD, N = 157). Optimum proportions between the radii of parent (r0) and branch (r1 and r2) vessels in the internal carotid artery system were verified in normal carotid angiographs up to four branch generations, according to the theoretical equation r0(3) = r1(3) + r2(3) (r = 0.989, N = 174). No clear correlation was found between the measured branch angles, the relative branch cross-sectional area, and the theoretical optimum angles. CONCLUSIONS: This study demonstrates that the process of branching of the internal carotid artery system obeys the principle of minimum work, as the diameter exponent approximates 3. The principle of minimum work establishes strict functional relations between volumetric flow, flow velocity, and vessel radius. This model was extended to parametric optimization of branch angles, which has proved irrelevant in terms of functional optimization. Our results corroborate this finding. Shear stress-induced endothelial mediation seems to be the regulating mechanism for the maintenance of this optimum vessel design. The magnitude of wall shear stress is the same at every point in a vascular network obeying the principle of minimum work, because the flow rate influences the shear stress proportionally to the third power of the vessel radius. This observation has implications for understanding the remodeling of the cerebral vascular network in the presence of arteriovenous malformations and for the pathogenesis of saccular aneurysms. PMID- 8446973 TI - Causes of urinary incontinence after acute hemispheric stroke. AB - BACKGROUND AND PURPOSE: We prospectively studied bladder function in stroke patients to determine the mechanisms responsible for poststroke urinary incontinence. METHODS: Fifty-one patients with recent unilateral ischemic hemispheric stroke admitted to a neurorehabilitation unit were enrolled. The presence of urinary incontinence was correlated with infarct location, neurological deficits, and functional status. Urodynamic studies were performed on all incontinent patients. RESULTS: Nineteen patients (37%) were incontinent. Incontinence was associated with large infarcts, aphasia, cognitive impairment, and functional disability (p < 0.05) but not with age, sex, side of stroke, or time from stroke to entry in the study. Urodynamic studies, performed on all 19 incontinent patients, revealed bladder hyperreflexia in 37%, normal studies in 37%, bladder hyporeflexia in 21%, and detrusor-sphincter dyssynergia in 5%. All of the patients with normal urodynamic studies were aphasic, demented, or severely functionally impaired. All of the patients with hyporeflexic bladders had underlying diabetes or were taking anticholinergic medications. Forty-six percent of incontinent patients treated with scheduled voiding alone were continent at discharge compared with 17% of patients treated pharmacologically. CONCLUSIONS: There are three major mechanisms responsible for poststroke urinary incontinence: 1) disruption of the neuromicturition pathways, resulting in bladder hyperreflexia and urgency incontinence; 2) incontinence due to stroke related cognitive and language deficits, with normal bladder function; and 3) concurrent neuropathy or medication use, resulting in bladder hyporeflexia and overflow incontinence. Urodynamic studies are of benefit in establishing the cause of incontinence. Scheduled voiding is a useful first-line treatment in many cases of incontinence. PMID- 8446974 TI - Absence of elevation of big endothelin in subarachnoid hemorrhage. AB - BACKGROUND AND PURPOSE: Endothelin peptides are potent vasoconstrictors and thus are seen as potential cause of cerebral vasospasm after subarachnoid hemorrhage (SAH). Earlier reports showed elevated or normal endothelin levels in plasma and cerebrospinal fluid in patients suffering from SAH. The present study was designed to determine whether endothelin is a causal factor in SAH. METHODS: We studied 11 patients with acute SAH. Seven of these 11 patients had a proven aneurysm and six had experienced vasospasm. Big endothelin levels were determined by a radioimmunoassay recognizing the C-terminal peptide (normal range, 1-11 fmol/ml). RESULTS: There were no elevations of big endothelin in the 59 plasma samples and the 17 simultaneously estimated cerebrospinal fluid samples. Differences between plasma and cerebrospinal fluid did not reach significant levels. Big endothelin values between patients with and without vasospasm showed no significant differences. CONCLUSIONS: Our findings suggest that plasma elevation of the endothelins is not reproducible in SAH and that big endothelin is unlikely to be a causal plasma factor in the complex multifactorial development of vasospasm after SAH. PMID- 8446975 TI - Data analysis in behavioral cerebral blood flow activation studies using xenon 133 clearance. AB - BACKGROUND AND PURPOSE: Three mainstream strategies exist to detect the responses of regional cerebral blood flow to functional activation. We tested the significance of changes in raw regional cerebral blood flow data, regional cerebral blood flow data normalized by division by global cerebral blood flow (dependent model of the regional-to-global cerebral blood flow relation), and regional cerebral blood flow data treating global cerebral blood flow as a covariate (independent model). Both latter models attempt to enhance regional sensitivity by removing global effects. We examined the sensitivity and pitfalls of these three strategies in behavioral activation studies. METHODS: These three strategies of data analysis were applied to changes in regional cerebral blood flow induced by a visuospatial problem-solving task in 38 healthy subjects as measured by the intravenous xenon-133 method with 32 stationary detectors. RESULTS: Mental activation increased blood flow in all regions of interest. Raw data were most sensitive and reliable to detect responses to mental stimulation. Both the independent and dependent models to remove global effects were less sensitive and falsely indicated deactivation in regions that were clearly stimulated. CONCLUSIONS: In behavioral activation paradigms, safe data analysis should be restricted to using raw regional cerebral blood flow increases without normalization or separation of global from regional effects. Studies using complex stimulation tasks should be scrutinized for global cerebral blood flow effects confounding regional responses. PMID- 8446976 TI - Subarachnoid hemorrhage and endothelial L-arginine pathway in small brain stem arteries in dogs. AB - BACKGROUND AND PURPOSE: Experiments were designed to determine the effect of subarachnoid hemorrhage on endothelium-dependent relaxations in small arteries of the brain stem. A "double-hemorrhage" canine model of the disease was used, and the presence of vasospasm in the basilar artery was confirmed by angiography. METHODS: Secondary branches of both untreated basilar arteries (inner diameter, 324 +/- 11 microns; n = 12) and arteries exposed to subarachnoid hemorrhage for 7 days (inner diameter, 328 +/- 12 microns; n = 12) were dissected and mounted on glass microcannulas in organ chambers. Changes in the intraluminal diameter of pressurized arteries were measured using a video dimension analyzer. RESULTS: In untreated arteries, 10(-11) to 10(-7) M vasopressin, 10(-10) to 10(-6) M bradykinin, and 10(-9) to 10(-6) M calcium ionophore A23187 caused endothelium dependent relaxations. At 10(-6) and 3 x 10(-4) M the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) abolished relaxations to vasopressin and produced small but significant rightward shifts of the concentration-response curves to bradykinin and A23187. At 10(-3) M L-arginine prevented the inhibitory effect of L-NAME. Subarachnoid hemorrhage abolished relaxations to vasopressin but did not affect relaxations to bradykinin or A23187. CONCLUSIONS: These studies suggest that in small arteries of the brain stem vasopressin causes relaxations by activation of the endothelial L-arginine pathway. This mechanism of relaxation is selectively inhibited by subarachnoid hemorrhage. Preservation of endothelium-dependent relaxations to bradykinin and A23187 is consistent with the concept that small arteries are resistant to vasospasm after subarachnoid hemorrhage. PMID- 8446977 TI - Hemodynamic and metabolic effects of flunarizine in experimental subarachnoid hemorrhage in dogs. AB - BACKGROUND AND PURPOSE: Cerebral blood flow and oxygen metabolism were measured and a cerebral angiography was performed in dogs with experimental subarachnoid hemorrhage to assess the relation between arterial narrowing (vasospasm) and the fall of blood flow. Cerebral blood volume and the cerebrovascular CO2 reactivity were also measured to estimate the cerebrovascular reserve. Several groups of dogs were treated with flunarizine in different regimens to assess its possible therapeutic effect. METHODS: The experiments were performed in the three hemorrhage canine model for subarachnoid hemorrhage. Cerebral blood flow and cerebral oxygen metabolism were measured in anesthetized (nitrous oxide) dogs using positron emission tomography in combination with the 15O steady-state method. Basilar artery diameter was evaluated by digital subtraction angiography. RESULTS: In normal dogs, cerebral blood flow, oxygen consumption, and oxygen extraction ratio were 46.4 +/- 9.0 ml/100 ml per minute, 3.65 +/- 0.76 ml/100 ml per minute, and 39.9 +/- 3.4%, respectively; basilar artery diameter was 1.33 +/- 0.25 mm. Repeated subarachnoid blood injection (3 x 5 ml) reduced basilar artery diameter to < 20% of normal (p < 0.01). Cerebral blood flow was reduced by only 25% (p < 0.001); oxygen consumption was preserved at a low normal level by a 29% compensatory increase of the oxygen extraction (p < 0.001). Cerebral blood volume and cerebrovascular CO2 reactivity remained nearly normal. Early (after the first blood injection) peroral treatment with flunarizine (0.5 mg/kg daily) resulted in less severe basilar artery narrowing (56% of normal; p < 0.05 versus untreated). However, this treatment had no effect on cerebral blood flow, blood volume, oxygen consumption, and extraction. CONCLUSIONS: The observed fall of cerebral blood flow in experimental subarachnoid hemorrhage is not related to arterial narrowing but to an increased cerebrovascular resistance at the level of the small parenchymal vessels, and the latter, in contrast to arterial narrowing, is unaffected by flunarizine. PMID- 8446978 TI - Cerebral autoregulation during moderate hypothermia in rats. AB - BACKGROUND AND PURPOSE: Little is known about the effects of hypothermia on cerebral autoregulation. The present study was designed to examine cerebral blood flow responses to controlled hemorrhagic hypotension in normothermic and hypothermic rats. METHODS: Cortical blood flow was measured with a laser-Doppler flowmeter in halothane-anesthetized rats assigned to one of three groups: normothermic group 1 (n = 8) with a pericranial temperature of approximately 36.5 degrees C or hypothermic group 2 (n = 8) or group 3 (n = 8) with a pericranial temperature of approximately 30.5 degrees C. In group 2, a PaCO2 of approximately 40 mm Hg was maintained without correction for body temperature. To evaluate the role of PaCO2, in group 3 animals PaCO2 was kept at approximately 40 mm Hg as corrected for body temperature. In all animals, the mean arterial blood pressure was reduced by hemorrhage in increments of 10 mm Hg every 2 minutes. RESULTS: In group 1 animals, a typical autoregulatory curve was observed with cerebral blood flow first falling at or below 75% of baseline at a mean arterial pressure of 57 +/- 15 mm Hg (mean +/- SD). Absolute normotensive cerebral blood flow in group 2 fell to < or = 75% of baseline at a mean arterial pressure of 73 +/- 21 mm Hg. In group 3, no evidence of autoregulation was seen. Cerebral blood flow reached values < or = 75% of baseline at a mean arterial pressure of 82 +/- 14 mm Hg, whereas calculated cerebrovascular resistance failed to show any compensatory vasodilation as the mean arterial pressure decreased. CONCLUSIONS: Different PaCO2 management schemes used during hypothermia may have profound effects on cerebral blood flow and on autoregulation. If PaCO2 is maintained at 40 mm Hg after correction for temperature, autoregulation is abolished. If uncorrected PaCO2 is maintained at approximately 40 mm Hg, some degree of autoregulation is preserved, albeit with a right-shifted "knee." PMID- 8446979 TI - Sustained decrease in brain regional blood flow after microsphere embolism in rats. AB - BACKGROUND AND PURPOSE: An experimental model that induces sustained ischemia and infarction may provide useful information relevant to prevention of the development of ischemic brain disease. The purpose of the present study was to elucidate the pathophysiological consequences of cerebral blood flow under sustained cerebral ischemia or oligemia and infarction in rats after microsphere embolism. METHODS: We injected 900 microspheres (48 microns in diameter) into the right internal carotid artery of 146 rats and determined the time course of changes in blood flow of the cerebral cortex, striatum, and hippocampus of both hemispheres by the hydrogen clearance method for a period of 28 days after the operation. Infarct area was determined by triphenyltetrazolium chloride staining and hematoxylin and eosin staining methods. RESULTS: Cortical and striatal blood flow of the right hemisphere of microsphere-injected rats was significantly decreased after the embolism, and this was sustained throughout the experiment. Hippocampal blood flow of the microsphere-injected hemisphere was also decreased on days 1 and 3 but tended to return toward control levels thereafter. In the left hemisphere, reduction in regional blood flow was detected in the cortex and hippocampus on day 1 and the striatum on day 3. A triphenyltetrazolium chloride unstained area had developed by day 3 after the embolism. The extent of the area was similar to that on days 7 and 28. Microscopic examination revealed degenerative areas scattered mainly in the parietotemporal cortex, corpus callosum, hippocampus, thalamus, and lenticular nucleus of the embolized hemisphere, demonstrating the induction of widespread necrosis after embolism. CONCLUSIONS: Microsphere embolism resulted in a sustained decrease in regional blood flow and production of cerebral infarction in the brain regions of the microsphere-injected hemisphere. PMID- 8446980 TI - Brain pHi, cerebral blood flow, and NADH fluorescence during severe incomplete global ischemia in rabbits. AB - BACKGROUND AND PURPOSE: The aim of this experiment was to study the serial changes in brain intracellular pH, cerebral blood flow, and the oxidation/reduction level of intramitochondrial nicotinamide adenine dinucleotide fluorescence across the cortical surface during severe incomplete global ischemia. METHODS: Reduced nicotinamide adenine dinucleotide fluorescence and brain intracellular pH using the pH-sensitive indicator umbelliferone were measured with in vivo panoramic fluorescence imaging of the cortical surface. Cerebral blood flow was measured with the clearance of both umbelliferone and xenon-133. Fifteen minutes of severe incomplete global ischemia was produced by temporary occlusion of the innominate, left carotid, and subclavian arteries in five fasted New Zealand White rabbits. RESULTS: Baseline brain intracellular pH was homogeneous over the exposed cortex, measuring 7.00 +/- 0.02, while cerebral blood flow was 48.0 +/- 2.6 ml/100 g/min. During 15 minutes of ischemia, cerebral blood flow measured 6.3 +/- 1.8 ml/100 g/min and brain pH declined to 6.61 +/- 0.02 (p < 0.005); in addition, there were acidotic foci with pH measuring 6.40 +/ 0.10. During reperfusion, there was an initial normalization of brain intracellular pH without an alkaline shift followed by a recurrent cortical acidosis of pH 6.88 +/- 0.06. There was a heterogeneous pattern of fluorescence that increased significantly following 60 minutes of reperfusion, coinciding with a postischemic hypoperfusion. The hypoperfusion was a uniform reduction in cerebral blood flow over the brain's surface, with reductions of 42.5% and 44.2% at 30 and 45 minutes, respectively. CONCLUSIONS: During incomplete global ischemia there is a heterogeneous pattern of brain intracellular pH and reduced nicotinamide adenine dinucleotide changes that do not correlate with changes in cortical blood flow. The acidotic foci that were approximately 0.2 pH units more acidotic than the surrounding cortex may be the result of continued glucose delivery under anaerobic conditions. The degree of reduced nicotinamide adenine dinucleotide fluorescence suggests that the cortex is most vulnerable to metabolic failure after 60 minutes of reperfusion following severe incomplete global ischemia. The heterogeneous pattern of brain intracellular pH and reduced nicotinamide adenine dinucleotide changes suggest that there may be a selective vulnerability of cortical tissue to an ischemic challenge. PMID- 8446981 TI - Measurement of cerebrovascular changes in cats after transient ischemia using dynamic magnetic resonance imaging. AB - BACKGROUND AND PURPOSE: Hemodynamic changes associated with acute ischemia cannot be measured with conventional nuclear magnetic resonance imaging. In this study, we used dynamic susceptibility-contrast magnetic resonance imaging to measure the changes in vascular transit time and relative cerebral blood volume in a feline occlusion-reperfusion model. METHODS: Dynamic susceptibility-contrast measurements were obtained before and during 10 minutes of global cerebral ischemia and for up to 3 hours after the onset of reperfusion. A cerebral blood flow index was calculated from the vascular transit time and relative cerebral blood volume measurements. Functional maps were constructed to demonstrate the regional hemodynamic differences resulting from the induced ischemia. RESULTS: During the early phase after reperfusion, both the relative cerebral blood volume and blood flow index rose sharply, followed by a fall to near-basal levels at 45 minutes (1 x control and 1.3 x control, respectively). Thereafter, the volume rose slowly, whereas the flow index continued to drop. At 3 hours, cerebral blood volume had reached 1.6 times its control value, whereas the flow index had returned to its base value. CONCLUSIONS: The hemodynamic behavior we observed in our model reflects the independent responses of the cerebral blood volume and flow index to ischemic insult. Measurements acquired by our method were consistent with the temporal behavior reported in previous radionuclide studies. Susceptibility-contrast nuclear magnetic resonance tomographic imaging proved to be valuable in detecting and quantifying both immediate and subsequent changes in the hemodynamic state of the ischemic and hyperemic feline brain. PMID- 8446982 TI - Dexamethasone prevents cerebral infarction without affecting cerebral blood flow in neonatal rats. AB - BACKGROUND AND PURPOSE: We recently demonstrated that pretreatment with the synthetic glucocorticoid dexamethasone prevents hypoxic-ischemic brain damage in neonatal rats. Presently, we examine whether this protective effect of dexamethasone is due to an improvement in local cerebral blood flow. METHODS: Neonatal rats were treated with either vehicle or 0.1 mg/kg i.p. dexamethasone 24 hours before hypoxia-ischemia (right carotid artery occlusion +3 hours of 8% O2). Cerebral blood flow was measured with [14C]iodoantipyrine autoradiography after either 2 (n = 17) or 3 (n = 15) hours of hypoxia-ischemia. Additional animals (n = 20) were perfusion-fixed 3 days after hypoxia-ischemia. The area of cerebral pathological changes was measured from hematoxylin and eosin-stained coronal sections taken at three different levels. RESULTS: Pathological outcome differed between groups. In vehicle-treated rats, sections from anterior, mid, and posterior portions of the cerebrum all had extensive infarction or cellular necrosis ipsilateral to the occlusion (mean areas of damage were 62.6 +/- 10%, 70.2 +/- 9%, and 54.2 +/- 8%, respectively). However, in dexamethasone-treated animals, brain damage in sections at corresponding levels was minimal (0%, 1.6 +/ 2%, and 1.5 +/- 1%, respectively; p < 0.0002). In contrast to the pathological results, cerebral blood flow was equivalent in the dexamethasone- and vehicle treated groups. After either 2 or 3 hours of hypoxia, cerebral blood flow was reduced 60-80% ipsilateral to the carotid artery occlusion in animals treated with either vehicle or dexamethasone. CONCLUSIONS: Despite ischemic levels of cerebral blood flow, pretreatment with dexamethasone prevents cerebral damage in neonatal rats. Instead of improving local cerebral perfusion, dexamethasone presumably acts via peripheral or central glucocorticoid receptors to produce some alteration in the brain that decreases its susceptibility to hypoxia ischemia. PMID- 8446983 TI - Effects of repeated cerebral ischemia on extracellular amino acid concentrations measured with intracerebral microdialysis in the gerbil hippocampus. AB - BACKGROUND AND PURPOSE: To clarify the role of elevated extracellular amino acid concentrations during ischemia on the cumulative neuronal damage after repeated cerebral ischemic insults, using a microdialysis technique we measured concentrations of the amino acids glutamate, glutamine, glycine, taurine, and gamma-aminobutyric acid in the gerbil hippocampus over three 2-minute forebrain ischemic insults induced at 1-hour intervals. METHODS: Under light anesthesia, the bilateral common carotid arteries were occluded with aneurysm clips at 1-hour intervals. Samples were collected by microdialysis at 10-minute intervals, and the amino acid concentrations were determined using a high-performance liquid chromatography system. RESULTS: During and immediately after the first ischemic insult, concentrations of glutamate, glycine, and taurine, but not glutamine, increased significantly. Glutamate and taurine concentrations rose again during the second and third ischemic insults, but the increases were smaller than those during the first insult. By contrast, glutamine concentrations increased slightly but significantly during the second and third ischemic insults. The extracellular concentration of gamma-aminobutyric acid before the ischemic insults was below the level of detectability but increased markedly during each ischemic insult, with similar declines in the amounts released during later insults. Concentrations of all amino acids returned to baseline after 10 minutes of reperfusion and remained at baseline until the subsequent ischemic insult was induced. CONCLUSIONS: It is well established that glutamate released during ischemia plays a crucial role in ischemia-induced neuronal death. However, the present results indicate that cumulative neuronal damage following sublethal ischemic insults is not caused by an exaggerated release of excitatory amino acids during subsequent ischemic insults but strongly suggest that increased intracellular reactions leading to cell death play a major role. PMID- 8446984 TI - Hemorrhagic transformation in cardioembolic cerebral infarction. AB - BACKGROUND AND PURPOSE: Because the frequency of hemorrhagic transformation of cerebral infarcts is still a matter of controversy, we performed a prospective magnetic resonance imaging study in a series of consecutive patients with cardioembolic stroke. SUMMARY OF REVIEW: Among 200 consecutive patients with transient ischemic attack or ischemic stroke, 41 were identified with a computed tomographically proven supratentorial infarct due to cardiogenic embolism. Magnetic resonance imaging (T1-weighted) was performed 3 weeks after the stroke in 35 of these 41 patients. Eight patients received anticoagulants. Magnetic resonance images showed hemorrhagic transformation in 68.6% (24) of the 35 infarcts, always without clinical deterioration. In a stepwise forward logistic regression analysis only the volume of infarction edema on the initial computed tomogram was linked significantly with the risk of hemorrhagic transformation (p = 0.037). Hemorrhages were a regular finding on magnetic resonance images of infarcts exceeding a volume of 10 cm3 (94.4%, 17 of 18). CONCLUSIONS: Hemorrhagic transformation is a regular finding in medium-sized and large cardioembolic infarcts. Thus, in therapeutic and preventive studies of acute stroke the severity, not the frequency, of hemorrhages into brain infarcts should be the matter of interest. PMID- 8446985 TI - Pseudotumor syndrome associated with cerebral venous sinus occlusion and antiphospholipid antibodies. AB - BACKGROUND AND PURPOSE: Antiphospholipid antibodies are known to be associated with increased risk of venous and arterial thrombotic events, including cerebral venous thromboses. Pseudotumor syndrome can be produced by cerebral venous thrombosis. A patient with cerebral venous thrombosis associated with antiphospholipid antibodies who exhibited pseudotumor syndrome is reported. CASE DESCRIPTION: A 49-year-old man who noted visual blurring and persistent vertical wavy lines in his fields of vision was found to have papilledema. Cerebrospinal fluid values were normal except for an opening pressure increase to 510 mm of fluid. His visual symptoms improved with lumbar puncture and the use of acetazolamide. Imaging studies showed that the transverse sinus was occluded completely on the left and partially on the right and that there was a small left cerebellar cortical venous infarction. CONCLUSIONS: Antiphospholipid syndrome should be considered in the differential diagnosis of pseudotumor syndrome related to cerebral venous thrombosis. PMID- 8446986 TI - Fulminant cerebral infarctions with membranous nephropathy. AB - BACKGROUND: Arterial thromboses, including cerebral infarction, are a rare complication of the nephrotic syndrome. SUMMARY OF REPORT: A 37-year-old woman presented with right upper extremity ischemia, left middle cerebral artery thrombosis, and right cerebellar infarction. She quickly herniated, and postmortem evaluation revealed membranous nephropathy. Increased fibrinogen and decreased free protein S levels were noted. CONCLUSIONS: Membranous nephropathy can lead to rapidly progressive cerebral infarctions, with possible fatality. There is not a unifying hematologic explanation for the strokes seen with nephrotic syndrome. PMID- 8446987 TI - Confusing stroke terminology: watershed or borderzone infarction? PMID- 8446988 TI - Treatment of cerebellar infarction by decompression suboccipital craniectomy. PMID- 8446989 TI - Spontaneous vertebral artery dissection initially revealed by a pain in one upper arm. PMID- 8446990 TI - Bilateral internuclear ophthalmoplegia, ataxia, and tremor from a midbrain infarction. PMID- 8446991 TI - [Old and young: an underexposed relationship]. PMID- 8446992 TI - [Dynamics of cognitive abilities in the course of active lifespan]. AB - Behavioral effects of cognitive aging and the meaning of experience are compared. Relating the process of aging to biological and functional decay does not do justice to the accumulation of knowledge and abilities over the active lifespan. Human development is a continuous process of growth and decline. It accounts for both gain and loss of cognitive abilities. From this perspective human capacities are not static but composed of a changing set of abilities which grow and decline over the life span. Despite decreasing capacity with age, reserve capacity may be sufficient to cope with normal task demands. Finally, it is illustrated how experience of older workers may contribute to the design of training programs. PMID- 8446993 TI - [Activity level, boredom, health and participative climate in nursing homes]. AB - In this paper an analysis is presented of factors accounting for differences in levels of boredom and activities of residents of homes for the aged. Eighty respondents in two homes for the aged were interviewed. Results indicate that residents with a positive perception of the participatory climate report lower levels of boredom but do not participate in activities more often than other residents. Moreover, persons who report psychological distress report higher levels of boredom. Other factors such as age, gender and level of activity do not seem to be related to boredom. It also appears that actual participation in activities is only predicted by age and two health indicators: health perception and ADL/HDL score. Persons who are younger and persons who report a better health situation participate more often in activities. PMID- 8446994 TI - [Significance of grandparents for young-adult grandchildren]. AB - Do young adult grandchildren find their grandparents important? What are the meanings that grandparents seem to have for these grandchildren? Those were the leading questions in the present study. Subjects were 239 university students (mean age: 19.5 years). They completed the Grandparents Meaning Scale, a recently developed 82-item instrument which probes for 11 a priori dimensions of meaning of grandparents for grandchildren: (I) Reliable alliance, (2) Affection and emotional support, (3) Reassurance of worth, (4) Practical and financial support, (5) Link with the past, (6) Acquaintance with aging, (7) Mentor and role-model, (8) Kinkeeper, (9) Mediator between children and parents, (10) Substitute caregiver, and (11) Distant figure. Subjects rated the importance and meaning of 222 grandmothers and 159 grandfathers. The results confirmed earlier findings. Young adult grandchildren generally found their grandparents important. Grandparents were valued because they provide their grandchildren with reassurance of worth and emotional support, and link their lives to the historical past. Grandmothers received higher scores than grandfathers on seven scales (1-4, 8-10). Grandfathers had higher scores on just two of the scales (5 and 11). Gender differences emerged with regard to the ratings of the grandmothers only. Girls had higher scores than boys on eight scales (1-3, 5, 7 10) and boys had a higher score on just one scale (11). PMID- 8446995 TI - [Treatment with botulinum toxin of patients with focal dystonia]. PMID- 8446996 TI - [Torticollis treated with botulinum toxin]. AB - The effect of botulinum toxin A treatment was studied in patients with idiopathic torticollis. Twenty patients with idiopathic torticollis received electromyographically guided intramuscular botulinum toxin A into the hyperactive neck muscles. In all, 48 treatments were given. The injections were repeated with intervals of 11 to 35 weeks (mean 18.7 weeks). The grade of improvement was estimated subjectively using a visual analogue scale. An overall improvement of 55% compared with the status before treatment was found. The best result obtained in each individual patient varied from 20% to 84% (mean 66%). The effect of the treatment began to wear off after eight to 22 weeks (mean 11.5 weeks). The side effects consisted of short term dysphagia in two patients. The administration of botulinum toxin in idiopathic torticollis is a safe and beneficial treatment with few side effects. The EMG guidance of injections proved to be helpful as it restricted the injections into muscles with electromyographic hyperactivity, thereby economizing the amount of toxin given. It is doubtful if double-blind studies of botulinum toxin can be undertaken due to the marked muscular wasting and weakness caused by the injections. PMID- 8446997 TI - [Gallstone and colorectal cancer. There is a connection, but not cholecystectomy]. PMID- 8446998 TI - [Cystic fibrosis. From clinical diagnosis to a mutation specific test]. AB - By use of classical linkage analysis and modern DNA technology the gene for cystic fibrosis (CF) was mapped to the long arm of chromosome 7 in 1985. Cloning of the entire gene (CFTR = Cystic Fibrosis Transmembrane Conductance Regulator) was published in 1989. The most common mutation (delta F508) is a three base pair deletion in exon 10, which results in a protein without the amino acid phenylalanine at position 508. The frequency of this mutation varies among different populations, ranging from 45% in the Mediterranean countries to a height in Denmark of 88% of the disease genes. More than 150 different mutations have been identified so far, most of which are very rare. CF is one of the most common severe inherited diseases, but the cloning of the gene and identification of the mutations give great possibilities for prevention permitting both carrier and prenatal diagnosis. The function of the CFTR protein is still not fully known. However, the amino acid sequence of the protein is highly homologous to those of several membrane proteins. In vitro transfection experiments indicate that it constitutes a chloride channel. Recently in vivo experiments involving somatic gene therapy on rats have been successful. PMID- 8446999 TI - [Incidence of myocardial infarction in Denmark. Results from Dan-Monica 1982 1984]. AB - The mortality from ischemic heart disease in Denmark has changed from a steady increase towards a decrease also in younger males during the 1980s. During this period, the Glostrup Population Studies have registered the incidence of myocardial infarction, risk factor changes and changes in medical care in Copenhagen county (320,000 inhabitants) as part of WHO MONICA, which compares 39 centres in 26 countries. The incidence of myocardial infarction during the first three years, 1982-1984, of the Heart Register, DAN-MONICA at Glostrup Hospital, is reported. The register is complete and valid. If the age specific incidence of myocardial infarction in Denmark was as in this survey, the results indicate an age standardized incidence for the Danish population including all age groups over the age of 25 of 5.58 per 1000 per year (7.48 per 1000 adult males and 3.99 per 1000 adult females). PMID- 8447000 TI - [Preventive health examinations of pregnant women in Denmark. Anamnestic practice and discussion of prenatal diagnosis in early pregnancy examinations in general practice, birth clinics and birthing centers]. AB - In Denmark, pregnant women are offered antenatal care in a nationwide programme. This programme is organized around health examinations in general practice, hospital outpatient departments and at midwives' centres. During winter 1986 1987, a nationwide investigation of antenatal care was carried out. A random sample of approximately 1/3 of the general practitioners, all of the midwives who had antenatal consultations and the medical staffs of 26 departments of obstetrics and gynaecology received a questionnaire about content of a definite antenatal examination. 62% of the general practitioners, 63% of the doctors at the place of delivery and 86% of the midwives replied. Among the pregnant women, 92% replied from general practice, 84% from hospital outpatient departments and 91% from midwives' centres. The interviews about date of delivery and genetic counselling at early visits in general practice, hospital outpatient departments and at midwives' centres were in agreement with the nationwide guidelines. Employment of routine ultrasound scanning was not associated with less detailed history taking by the doctors at hospital outpatient departments, where ultrasound scanning was employed only on special indications. It was concluded that there was a considerable overlap between the interview about the date of delivery and genetic counselling at early visits in general practice and in hospital outpatient departments and, to some extent, at the midwives' centres. The sharing of responsibility for care of pregnant women by three professional groups requires specification of the content of the consultation. Official guidelines should be more specific about this point. PMID- 8447001 TI - [General practitioners and smoking. General practitioners' knowledge, attitudes and smoking habits and the relationship between these assessed by a questionnaire study in the county of Aarhus]. AB - The objects of the investigation were to investigate the smoking habits of general practitioners, their assessment of tobacco as a risk factor for ischaemic cardiac disease, attitudes to intervention to stop smoking and to assess whether there was a connection between these. The project was carried out as a questionnaire investigation in the County of Aarhus, where all of the general practitioners received questionnaires. A total of 313 general practitioners replied to the questionnaire which corresponds to 84% participation. 33% of the general practitioners smoked and nine were chain smokers. The majority of the general practitioners accepted that smoking was a risk factor for ischaemic heart disease and were prepared to make great efforts to combat smoking. A connection was present between smoking habits and attitudes: Non-smokers considered that smoking was of great significance as a risk factor for ischaemic heart disease and were prepared to make efforts to alter the smoking habits of their patients. General practitioners doubted the effect of their advice about stopping smoking. PMID- 8447002 TI - [General practitioners and prevention of ischemic heart disease]. AB - The object of this investigation was to examine general practitioners' attitudes to prophylaxis, assessment of the significance of a series of risk factors for the development of heart disease and how much emphasis they employed in attempting to alter the risk factors. In addition, the general practitioners' own health habits were investigated and it was assessed whether there was any connection between health habits and assessment of risk factors and the priorities given to these efforts. The general practitioners' advice and current behaviour as regards risk factors were investigated. The investigation was carried out as a questionnaire investigation in the County of Aarhus where all doctors received a questionnaire. A total of 313 general practitioners replied to the questionnaire which corresponds to a percentage participation of 84. The investigation revealed that general practitioners are interested in prophylaxis but find it difficult. By and large, general practitioners regarded the usual risk factors as being of great significance for the development of ischaemic heart disease and considered that it was important to alter these. A connection was present between their own health habits, assessment of risk factors and the priority awarded to these. Practitioners who had had their own serum cholesterol measured, considered that hypercholesterolaemia was important and awarded efforts to correct this greater priority than practitioners who had not had their serum cholesterol measured. The general practitioners abilities in taking case histories and giving dietary advice in cases of hypercholesterolaemia showed that they had only few deficiencies, but that there was a great scatter in their intervention limits for hypercholesterolaemia. PMID- 8447003 TI - [Prescription of benzodiazepines in general practice]. AB - General practitioners are responsible for about 90% of all prescriptions for psychotropic drugs which benzodiazepines account for approximately 75%. In order to obtain a quantitative and qualitative assessment of the consumption in Svendborg, all benzodiazepine prescriptions were registered during a two-month period (February and March 1990). A total of 3364 prescriptions were issued to 6% (2262 persons) of the population. Of these, 1837 (54.6%) were prescriptions for tranquillizers, 1272 (37.8%) for hypnotics and 255 (7.6%) for both tranquillizers and hypnotics. The prevalence of benzodiazepine users increased with age and women were responsible for about 2/3 of the total consumption. Small but frequent prescriptions were issued to the younger users of benzodiazepines while older users generally received prescriptions for greater quantities at longer intervals. One in four persons over 80 years of age used sedatives. On account of the pharmaceutical, social and economic consequences of the widespread use of benzodiazepines in the elderly population, restrain should be observed in prescribing benzodiazepines. PMID- 8447004 TI - [Oculomotor nerve paralysis in patients with rheumatic disease, possible causes and anatomical localization of the lesions]. AB - Oculomotor nerve paresis is a rare neurological manifestation in rheumatological disease. It is most commonly described in connection with systemic vascular disease such as polyarteritis nodosa, Wegener's granulomatosis and Behcet's disease but is rarely an isolated symptom. As in benign vascular and diabetic oculomotor paresis, the etiology of oculomotor paresis in rheumatic disease appears to be angiopathy and subsequent ischaemia in the nerve tissue. Two case histories are presented. Both of the patients had been recognized as having well defined rheumatological complaints without previous neurological manifestations. Both developed partial isolated affection of the oculomotor nerve with paresis of the levator palphebrae muscle and ptosis. The condition was interpreted as mononeuritis of vascular origin and the patients were treated with methylprednisolone parenterally (1 g methylprednisolone per 250 ml isotonic sodium chloride per 24 hours for a total of three days). In the subsequent discussion, the neuroanatomical relationships of the oculomotor nuclear complex in the mesencephalon are described together with the fasciculi and the course of the peripheral nerve. On the basis of selected case histories, the possible anatomical localization of the lesion in oculomotor paresis of vascular origin is discussed. PMID- 8447005 TI - [Elimination of Haemophilus influenzae type b meningitis after introduction of vaccination]. PMID- 8447006 TI - [Antibiotic prevention in meningococcal disease]. PMID- 8447008 TI - [Food allergy]. PMID- 8447007 TI - [Foot zone therapy and bronchial asthma]. PMID- 8447009 TI - [Were all occupationally conditioned complaints reported to the authority of occupational protection?]. PMID- 8447010 TI - [Protection of sensitive personal data--against what?]. PMID- 8447011 TI - [Reported occupation-related complaints on Fyn. A review of notifications of the authority on occupational protection, Kreds Fyn's County 1 January 1988-31 March 1989]. AB - In order to describe the pattern of notification of occupationally conditioned complaints including, the particular, variations in the frequencies of notifications between the general practitioners, the notifications to the Insurance Authorities in the Country af Funen during the period from January 1988 March 1989 were reviewed. A Total af 2.114 notifications were included. 53% of the notifications originated from general practice and were concerned mainly with complaints from the locomotor system. Specialists were responsible for 17% of the notifications which were primarily skin conditions. Hospital departments were responsible for 15%, primarily damage to hearing, and the clinic for Occupational Medicine was responsible for 14% of the notifications. The notifications were very unevenly distributed: Just under one fifth of the general practitioners were responsible for half of the notifications from general practice whereas one sixth of the practitioners did not make a single notification during the 15 month period. 56% of the patients desired to apply for compensation for occupational injury. These were, in particular, elderly, male patients with damaged hearing, toxic encephalopathy and neoplasms. 14% of the patients desired to remain anonymous. The frequency of notification from general practice decreased significantly during the period of registration. Where the entire material was concerned, a decrease was also concerned during the period but this was not significance at the 5% level. The decrease in the country as a whole also continued after the period of registration. PMID- 8447012 TI - [Occupation-related complaints in general practice on Fyn--occurrence, pattern of notification. A 3-month registration period, 1 September 1989-30 November 1989]. AB - The object of this investigation was to illustrate the occurrence of occupational injuries in general practice and the pattern of notification of occupationally conditioned complaints. Thirty-three general practitioners in Funen attempted to register all the consultations during day working hours during the period September-November 1989 on account of presumed occupational injuries by means of a multiple-choice form. A total of 393 consultations concerning 213 occupationally-conditioned complaints and 99 occupational accidents were registered, implying that 1.1% of all consultations during day working hours during the period af registration were concerned with occupational accidents and 0.7% with occupationally-conditioned complaints. 37% of the presumed occupationally-conditioned complaints were notified. The fraction of notifications was greatest among female patients and among the more severe, chronic and obviously occupationally-related cases. 63% were not notified. The commonest reasons for this were triviality, unproved causal connection or that further developments were awaited. In 15% of the non-notified cases, it was stated that notification was not anticipated to result in any consequences. It is concluded that occupational injuries constitute both quantitative and qualitative problems of considerable extent in general practice. Only a minority of the presumed occupationally-conditioned complaints were notified. Awareness of the objects of notification must be increased and motivation for notification must be increased by emphasizing the consequences of notification. PMID- 8447013 TI - [Adenosine in the diagnosis and treatment of tachycardia]. AB - The correct diagnosis of tachycardia is important for reasons of treatment and prognosis. Intravenous bolus injection of adenosine can be used to diagnose tachycardia as ventricular or supraventricular and to convert AV-nodal re-entry tachycardia as well as re-entry tachycardia due to an accessory pathway. The effect of adenosine on different types of tachycardia is demonstrated. A strategy is proposed for examination and treatment of patients with manifest tachycardia to improve diagnosis and remove bias to supraventricular tachycardia and underdiagnosis of ventricular tachycardia. PMID- 8447014 TI - [Diagnosis and treatment of injuries to the lateral ligaments of the ankle joint]. AB - Injury to the lateral ligaments of the ankle joint is one of commonest injuries seen in the casualty department. The diagnostic routines and treatment vary considerably from one hospital to another. The methods for precise diagnosis and treatment are reviewed and discussed and the main emphasis is placed on major prospective investigations. The authors suggest that the diagnosis should be made on the basis of the clinical examination and that, regardless of the degree of ligamental injury, treatment should consist of adhesive strapping. Primary identification of patients with prolonged symptoms is an unsolved problem since the degree of ligamental injury is not a reliable predictor. PMID- 8447016 TI - [Patient-controlled analgesia in children]. AB - In order to introduce intravenous patient-controlled analgesia (PCA) in children in the Department of Anaesthesiology and Intensive Care, Odense University Hospital, we evaluated the technique in 13 children following major orthopaedic or abdominal surgery. The pump (Pharmacia-Deltec, CADD-PCA) was loaded with 1 mg/ml morphine in a 50 milliliters cassette. A bolus dose of 25 micrograms/kg and a lock-out interval of eight minutes were the initial settings. The morphine dose used, pain scores and side effects were currently recorded. Ages ranged from 4-15 years (mean 10.5 years) and the method was used for a mean of 89 hours (range 57 144 hours) postoperatively. Morphine requirements averaged 9.5 microgram/kg/hour (range 5.4-15.6 microgram/kg/hour). Pain control was good and side effects were few and of minor nature. PCA is an effective and safe means of providing good quality analgesia in children. PMID- 8447015 TI - [Skiing injuries. Review over the winter of 1990-1991 in a clinic in the French Alps]. AB - The popularity of skiing has increased in recent years, producing an increase in the absolute number of ski injuries despite a decrease in the overall injury rate. A review of 620 injuries in a surgery in Val d'Isere, in the French Alps, during the winter season 1990-1991 confirmed the evolution in the epidemiology of ski injuries. In our study, fractures only constituted 11% of the ski lesions. The upper extremity was involved in 28% and the lower extremity in 49% of the injuries. 33% of the absolute number of injuries and 72% of the admissions to hospital were on account of knee injuries. More attention should be paid to the individual preparation of the skier. PMID- 8447017 TI - [Psychosocial outcome after individualized neuropsychological rehabilitation of patients with brain injuries]. PMID- 8447018 TI - [Sexual knowledge among women applying for abortion]. AB - A total of 589 women applying for termination of pregnancy completed a questionnaire about female anatomy and sexual information (46% replies). Of these 415 women had the pregnancy terminated in Hvidovre Hospital, Copenhagen (high abortion rate) and 174 in Aalborg Hospital in the northern Jutland (low abortion rate). The two groups showed great agreement in the replies. In 14% the sexual information was not acceptable and, especially among women under 20 years, the sexual information was poor. Only 13% of the women with poor sexual information considered that their knowledge should be increased, compared to 26% women with better knowledge. Most women received their first sexual information from their mothers and the general practitioners were the most used for further information. Most women were satisfied with the information given by their mothers and general practitioners. In conclusion, the present study did not explain the observed difference in abortion rate between the two regions. PMID- 8447019 TI - [AIDS--knowledge, behavior and attitude at the University of Aarhus in 1990. A questionnaire study]. AB - To describe knowledge, attitude and behaviour regarding AIDS among students and employees at the University of Aarhus an anonymous self-administered questionnaire survey was conducted in April 1990. Of the 2169 and 850 questionnaires to students and employees, respectively, 1548 (71.4%) and 568 (67%) were returned. The study group had an excellent knowledge about AIDS and the transmission of HIV-virus. However, when defining "risk behaviour" in relation to transmission of HIV-virus among heterosexuals as "> or = 2 sexual partners within the past year without using condoms" 27% of the male and 20% of the female students showed risk behaviour. Among employees the rate was highest (23%) among the male scientific staff than among the remainder (17%). It is concluded that risk behaviour was not related to age and occurred in spite of the fact that 42% of the students and 31% of the employees, who showed risk behaviour were also aware of a personal risk of being infected. There is still a need for information about AIDS, and future campaigns should be directed towards all age groups as risk behaviour is not only a phenomenon among young people. PMID- 8447020 TI - [Idiopathic bilateral paralysis of the diaphragm]. AB - The case of a 38-year old Caucasian man with acute irreversible idiopathic bilateral paralysis of the diaphragm is presented. The relevant diagnostic procedures are discussed. Paralysis of diaphragm during fluoroscopy in the supine position, observation of paradoxical movement of the anterior abdominal wall and upright position during sleep are the major characteristics of this condition. Elevation of both hemidiaphragms on thoracic X-ray during maximal inspiration, lack of phrenic nerve conduction, gradually increasing dyspnoea without ongoing infection or simultaneous vaccination and decreased functional status may further confirm the diagnosis. PMID- 8447021 TI - [Treatment of small-cell lung cancer]. PMID- 8447022 TI - [Elimination of methotrexate in sweat]. PMID- 8447023 TI - [Lithium and furosemide--interaction?]. PMID- 8447024 TI - [Autotransfusion--pro et contra]. PMID- 8447025 TI - [Solcotrans, a new autotransfusion system]. AB - Thirty-one patients scheduled to undergo aortic reconstruction were studied. 16 had aortic aneurysms and 15 required aortobifemoral grafts. The solcotrans unit comprises a rigid plastic container with an inner lining bag, into which blood is aspirated. When the bag is full (500 ml), the unit is inverted and blood is re infused through a 40 micron filter. Sixty-three percent of the blood transfused per-operatively and 41% peri-operatively was given with the solcotrans unit. Only minor changes in the coagulation parameters were seen. Blood cultures from ten solcotrans units were all negative. Two patients contracted pneumonia, and one cystitis. We conclude that the solcotrans system is safe to use when two-to four units of blood are transfused. Further studies are required to define its role when multitransfusions of blood are needed. PMID- 8447026 TI - [Gender--an important parameter in medical science]. AB - The fact that large areas of medical research have excluded women from studies and clinical trials has been criticised by many. It is also seldom mentioned in textbooks that the two sexes are biologically different. A series of examples of known differences between the sexes are given, as well as their biological and psychological implications for medical scientific theory and treatment. These examples are used to illustrate how incorrect treatment and discrimination of both women and men may take place, if the sex of the patient is not taken into account. PMID- 8447027 TI - [Examination and treatment in cerebrovascular insults. A population-based study from a rural district]. AB - A population-based survey of the use of different types of examination procedures and treatments of stroke is presented. The study area was a rural district with one local hospital. During a period of 2 1/2 years, 125 cases of first strokes and 29 recurrences were identified. The incidence of hospitalized first strokes in a population of 33,769 was 1.48 per 1000. The three week mortality was 27%. 30% of the patients were submitted to CT-scanning, and 25% were transferred to a specialist department. Two patients (1.6%) had surgery and 4.8% started anti coagulation treatment. The survival data are compared with a 50 year-old Danish survey. Better survival is seen among patients who are initially awake or drowsy. Initially semicomatose or comatose patients still have poor prognoses. 5% of all bed-days used by the population surveyed were used for the treatment of acute stroke. PMID- 8447028 TI - [Risk of lung cancer among foundry workers]. PMID- 8447029 TI - [Rheumatoid factor IgM analyses in Danish laboratories. An interlaboratory study]. AB - The aim this study was to compare the correlation between the rheumatoid factor analyses in Danish laboratories. Concentrations of rheumafactor IgM were found in 10 different sera at 17 different laboratories. Thirteen laboratories used the ELISA technique and four the nephelometry technique. Correlation between the laboratories using the same technique was acceptable in the interval 10 to 200 IU/ml. Concentrations were higher when the nephelometry technique was used compared with the ELISA technique. PMID- 8447030 TI - [The value of serological examination in neuroborreliosis]. AB - Over a period of 18 months, 155 patients with indications for lumbar puncture (LBP) on account of neurologic symptoms were examined for specific antibodies to Borrelia burgdorferi (BB) in the serum and for production of specific antibodies against BB in the cerebro-spinal fluid (CSF). Positive anti-BB-antibody production in CSF was found in one patient and the clinical manifestations were consistent with the third stage of neuroborreliosis (NB). Three patients with NB as a tentative diagnosis were found negative for anti-BB-antibody-production in the CSF, and a clinical reevaluation excluded NB as a final diagnosis. The study showed a very high predictive value of the test for anti-BB-antibody-production in the CSF both with positive and negative results. The results suggest further that NB is of a low incidence in Denmark and not often misdiagnosed in favour of more well known diseases. PMID- 8447031 TI - [Systolic blood pressure at rest and during submaximal and maximal exercise on ergometer bicycle. The value of automatic and auscultatory determination]. AB - Fifteen normal subjects participated in this comparison of systolic blood pressure measurement determined both automatically (AU) with the Kivex Ergometrics 900 and by the standard auscultatorically method (AM). Maximal exercise, was achieved by work performed on an electronically braked ergometer bicycle. In the first part of this study, simultaneous measurements of systolic blood pressure were made by the Kivex device and by the standard method at rest, every minute during exercise, and one minute after stopping exercise. The differences (two standard deviations) between AU and AM (n = 229) were +/- 19 mmHg at rest, +/- 15 mmHg at submaximal level, and +/- 49 mmHg at maximal exercise level. The acceptable difference was determined to +/- 15 mmHg by Bland and Altman. In the second part of this study, the differences between simultaneously measured auscultatoric systolic blood pressure by two observers (n = 205) was +/- 10 mmHg at rest, +/- 9 mmHg at submaximal level, and +/- 10 mmHg at the maximal exercise level. It can therefore be concluded that Kivex automatic blood pressure device, Ergometrics 900, is unable to measure accurately systolic blood pressure with sufficient agreement in normal subjects at the maximal stress level or at rest. However, at the submaximal exercise level, the Kivex device was able to measure systolic blood pressure with an acceptable agreement with the standard method. Therefore, the blood pressure results obtained by the Kivex device are highly influenced by the exercise level. The agreement between two observers using standard auscultatory method for systolic blood pressure measurement was found to be acceptable at all levels of exercise. PMID- 8447032 TI - [The effect of captopril, metoprolol and hydrochlorothiazide therapy in patients with non-insulin-dependent diabetes (NIDDM) and primary hypertension. A double blind, randomized cross-over study]. PMID- 8447033 TI - [Incidence of the presence of esophageal Candida albicans colonies in Danish population--especially related to symptoms and diseases in the esophagus and lung diseases]. PMID- 8447034 TI - [Measurement of the wound cavity area by means of PC based planimetry. The method and observer variations]. AB - A method for wound area measurement is presented. A wound cavity was cut in a chine of pork. A thin PVC plastic film was applied closely to the entire wound cavity surface and a line was drawn close to the cutaneous border with a marker pen. The film was then placed on a system of coordinates and coordinates were determined and entered into a PC-programme which calculated the area. No significant intra-or inter-observer variation appeared on analyses of variance between five observers each of whom performed three consecutive measurements (p > 0.2). Thus, employment of the method for clinical purposes seems feasible. PMID- 8447035 TI - [Sucralfate versus placebo in the treatment of abdominal wound abscesses]. AB - Twenty-seven patients were divided at random into two groups following abscess formation and complete reopening of the abdominal wound in a prospective double blind investigation to study the effect of topical sucralfate on the wound healing rate in secondary abdominal wounds. Fifteen patients were treated with sucralfate powder and 11 patients with placebo while one patient was excluded. The two groups were comparable as regards age, sex and factors predisposing to abscess formation. In the sucralfate group the median healing rate was 2.8 cm2/24 hours as compared with 2.4 cm2/24 hours in the placebo group (p = 0.92, Mann Whitney test). From this investigation, it is concluded that topical application of sucralfate powder does not appear to increase the rate of healing in secondary abdominal wounds after incision of a wound abscess. PMID- 8447036 TI - [Autologous multitransfusion with the Solcotrans system to a patient with ruptured aortic aneurysm and incompatible bank blood]. AB - We describe a patient with a ruptured aortic aneurism requiring immediate surgery where bank blood was incompatible. The Solcotrans autotransfusion system was used and eight units (each 500 ml) were given without complications. Multitransfusion with this system is only sparsely described in the literature. PMID- 8447037 TI - [Is sarcoidosis an infectious disease caused by mycobacteria?]. PMID- 8447038 TI - [Fibrillary glomerulopathy--a new disease?]. PMID- 8447039 TI - [Fatal traffic accidents among the elderly]. PMID- 8447040 TI - [Pyelonephritic scar formation]. AB - Pyelonephritic scars almost never develop after urinary tract infections alone, but require certain risk factors in addition. The most important risk factors are: vesicoureteral reflux, intrarenal reflux, obstructive uropathy, and nephrolithiasis. Most pyelonephritic scars develop in early childhood with the combination of vesico-ureteral reflux, intrarenal reflux, and urinary tract infections. Urinary tract infections alone almost never result in pyelonephritic scars. After the age of 3 years the risk developing pyelonephritic scars is not more than 10% in those with the combination of urinary tract infections and vesicoureteral reflux. In this age group the risk developing pyelonephritic scars is not altered by antireflux operation. PMID- 8447041 TI - [Radiologic findings in the kidney of children with severe reflux. Five-year comparative study of conservative and surgical treatment]. AB - The renal findings revealed by intravenous urography (IVU) in 306 children (73 boys, 233 girls) are reported. The children were seen at eight European centres and enrolled in an international study comparing medical and surgical management of children with urinary tract infection and severe vesico-ureteric reflux who were followed for 5 years. In all, 155 children were randomly allocated to medical and 151 to surgical treatment. The protocol and the investigative techniques were standardized, and randomization, data collection and analysis were performed centrally in Essen, Federal Republic of Germany. At entry 149 (49%) had established renal scarring (79 medical, 70 surgical). Presence of normal kidneys (105), areas of thinned parenchyma (52) and grade of reflux were also evenly distributed. IVU was repeated at 6, 18 and 54 months, and serial urine culture, 99mtechnetium-dimer-captosuccinic acid scans and plasma creatinine estimations were performed. Follow-up was complete in 272 children (89%). In 174 children (57%: 90 medical, 84 surgical) there was renal growth without morphological change. New renal scars developed in 19 children treated medically and 20 treated surgically; 12 (5 medical, 7 surgical) developed in previously normal kidneys. Six followed postoperative obstruction. No significant difference in outcome was found between medical and surgical management in terms of the development of new renal lesions or the progression of established renal scars. PMID- 8447042 TI - [Diagnosis in urinary tract infections]. AB - For a rational diagnostic work-up of urinary tract infections (UTI), a detailed history and a standardised examination of smear material, prostatic fluid and urine are essential. Examination of the urine is simple, with test strips, microscopic examination of the sediment and determination of the bacterial count by the dipstick procedure having proved their worth in practice. Isolation and identification of pathogens and the preparation of an antibiogram require special knowledge of microbiological techniques. Accurate evaluation of the urine and its constituents requires a knowledge of how the urine has been collected; we recommend spontaneously passed urine in men and young children, and catheter urine in women. Acute complicated and chronic recurrent UTIs require radiological studies and sonography. Occasionally, nuclear-medical investigations and angiography or CT may be necessary for detailed classification. In cases of obstruction of the lower UT or neurogenic problems with urinary bladder, urodynamic investigation and endoscopy must be performed. This stepwise diagnostic evaluation allows both optimal classification of the UTI and a saving in costs. PMID- 8447043 TI - [Current chemotherapy in urinary tract infection]. AB - Because of the many newly developed chemotherapeutics it is often hard to choose the most suitable substance for treatment of urinary tract infection (UTI). Substances for first-line oral treatment are the benzylpyrimidine/sulphonamide combinations, amino-penicillins, fluoroquinolones and cephalosporins. In severe infections any of these can be given i.v., as can amino-glycosides or the combination of imipenem and cilastin. It is easier to decide which substance to give before urine culture results are available if the local resistance patterns to the typical pathogens are known. Particular care is mandatory for risk groups such as children, pregnant women, immunocompromised patients and those with renal insufficiency. Before treatment clinical classification of UTI is necessary. In acute uncomplicated cystitis oral antibiotics should be given either as single shot therapy or over 3 days. In acute uncomplicated pyelonephritis therapy should last for 7 days or until 3 days after fever is gone. If enteral absorption is not guaranteed or in complicated cases of UTI, intravenous drugs should be used for 10-14 days until fever is gone or the complicating factor has been corrected. PMID- 8447044 TI - [Conservative drug therapy and surgical treatment of vesico-ureteral reflux. Current status, considerations and recommendations]. AB - Long-term results recorded in the Birmingham and International Reflux Study are reported, and the implications for pediatricians and urologists are discussed. The risk of scarring is similar after conservative and after operative treatment, and reflux persists after 5 years of chemotherapy in 65-76% of children with grade III and IV reflux. Spontaneous maturation after 1-2 years is rare, and there is no point in conservative treatment with serious problems during pregnancy. A list of indications with due consideration for the chances of maturation, duration of chemotherapy and the risks involved in operation is proposed. The risks are remarkably low in endoscopic antireflux procedures, especially with collegen, and therefore a wide spectrum of relative indications is recommended, especially for groups with persisting severe reflux after 1 year of chemotherapy or such problems as breakthrough urinary infection and poor compliance. PMID- 8447045 TI - [Gas-forming mycosis of the kidney]. AB - We report on the case of a 22-year-old heroin-dependent diabetic woman. She presented with a gas-forming fungal infection of the kidney caused by Candida tropicalis. The patient was successfully treated by conservative means. Problems in the diagnosis and therapy of this rare disease are discussed. PMID- 8447046 TI - [Imaging procedures in preoperative lymph node staging of invasive bladder cancer. Necessary or superfluous?]. AB - A staging programme for detection of lymph node involvement before radical cystectomy has been carried out in 22 patients. The programme includes: intravenous pyelography, chest X-ray, abdominal sonography, bone scan, CT and MRI. Also an immunoscintigraphic examination using monoclonal anti-CEA antibody (TUMAK BW 421/26) was done in every patient. Preoperative lymph node staging using CT, MRI and immunoscintigraphy was compared with post-operative histological staging: a total of 5 patients were found to have lymph node involvement. In none of them had lymph node involvement been predicted on the basis of CT, MRI or immunoscintigraphy. PMID- 8447047 TI - [Carcinosarcoma of the urinary bladder]. AB - A female patient is presented who had a large carcinosarcoma of the urinary bladder that became clinically manifest only 2 months before treatment. The initial treatment by transurethral resection was followed by radical cystectomy; 7 months postoperatively the patient died of local tumour recurrence with widespread metastases. Carcinosarcoma of the urinary bladder is a rare tumour with a poor prognosis. The majority of such tumours are not diagnosed until tumour growth is already far advanced. Owing to the small number of cases there is no clinically proven form of management. In contrast with superficial transitional cell carcinoma of the bladder, superficial carcinosarcoma of the bladder has always invaded the lamina propria, since in addition to the carcinomatous degeneration of the mucosa, sarcomatous degeneration of the underlying submucosal stroma is also present. Any local surgical treatment, such as TUR or partial cystectomy, involves the risk of incomplete tumor removal, because the sarcomatous elements typically invade the submucosa while the overlying mucosa remains intact. Therefore, radical cystectomy appears to be the treatment of choice for both superficial and invasive carcinosarcoma of the urinary bladder. PMID- 8447048 TI - [The role of bacterial adhesion in urinary tract infections]. AB - Bacteria adhere to and colonize almost any surface. The mechanism by which bacteria interact with the mucosal surface appears to involve specific molecular ligands or adhesins on the surface of the bacteria that interlock with specific receptor molecules on the surface to be colonized. Material adhesion allows the microorganisms to resist being washed away by the fluids and secretions that bathe mucosal surfaces and is a necessary prerequisite to growth, colonization, and subsequent infection. Many examples of the role of bacterial adherence to tissues of the host have been reported in the literature. The classic study is that of Smith and Linggood, who demonstrated that toxin-producing enteropathogenic Escherichia coli, which cause diarrhoea in swine, adhere selectively to the mucosal surfaces of the small intestine. Adherence is mediated by hair-like pili projecting from the surface of the cells. Production of these pili is controlled by a specific plasmid, the loss of which renders the cells avirulent although they continue to produce toxin. In addition, antibody to the pilus antigen prevents adherence and protects piglets against challenge with the piliated organisms. Thus, the adhesin is an essential virulence factor in enteropathogenic E. coli infections in swine. Similar studies in a variety of diseases including enterotoxigenic E. coli infections in men and rheumatic fever support the concept that specific bacterial adherence to host tissues is an important characteristic of many pathogenic microorganisms. PMID- 8447049 TI - Competition animals: the welfare implications assessed. PMID- 8447050 TI - Prevalence of antibodies to Neospora caninum in a population of urban dogs in England. AB - Of 163 dogs, randomly selected from those examined at the University of Liverpool Small Animal Hospital, 12.9 per cent had antibody titres > or = to 1/200 to Neospora caninum in an indirect fluorescent antibody test. None was apparently suffering clinical neosporosis. There was no association between the occurrence of neospora antibodies and either toxoplasma antibodies measured by the dye test, sex, age, type of feeding or the presence of other dogs in the household. Antibody was detected at titres > or = to 1/200 in nine breeds, suggesting that there is a substantial level of subclinical infection in British dogs. PMID- 8447051 TI - Effect of catching method and lighting intensity on the prevalence of broken bones and on the ease of handling of end-of-lay hens. AB - Five catching methods were compared in terms of their effect on the proportion of battery hens which had bones broken when they were removed from battery cages. In addition the effect of tier, lighting intensity during lay and lighting intensity during handling on the prevalence of fractures at catching and on old fractures which occurred during lay was evaluated. Catching and removing hens by one leg from the cages resulted in 11 to 14 per cent of the birds acquiring a broken bone, whereas catching and removing each bird by two legs resulted in 5 per cent of the birds acquiring a freshly broken bone. Removing more than one bird at a time from the cage tended to cause more skeletal damage than removing them individually, and incorporating a wooden breast support slide over the feed trough had no effect on the prevalence of broken bones. Catching birds in the top tier of a three-tiered battery unit was more difficult than for the middle or bottom tiers. When the light intensity at catching was the same as that during lay birds were more difficult to catch than when the light intensity was changed, but the effects were insufficient to affect the prevalence of damage to the skeleton. PMID- 8447052 TI - Does equine motor neuron disease exist in the United Kingdom? PMID- 8447053 TI - Comparative efficacies of various anthelmintics against benzimidazole-resistant strains of sheep nematodes. PMID- 8447054 TI - BVA/Kennel Club/International Sheepdog Society Eye Scheme: notes on procedure. PMID- 8447055 TI - Supply of vaccines. PMID- 8447056 TI - Husk in heifers. PMID- 8447057 TI - Retention of progestogen sponges in ewes. PMID- 8447058 TI - Equine influenza in Hong Kong. PMID- 8447059 TI - Incontinence in giant schnauzers. PMID- 8447060 TI - Effect of subclinical coccidiosis in kids on subsequent trichostrongylid infection after weaning. AB - Seven-week-old female kids of the Murciana-Granadina breed naturally infected with coccidia were superinfected with a multispecific Eimeria inoculum (300,000 oocysts) or treated to control the coccidial infection with Amprolium (50 mg kg-1 liveweight day-1; 4 days every 14 days); 80 days later both animal groups received 2500 third-stage larvae of a sheep-derived mixture of Trichostrongylus colubriformis (50%), Teladorsagia circumcincta (40%) and Haemonchus contortus (10%). Kids experimentally superinfected with Eimeria showed reduced food intake at the early patency period, higher numbers of oocysts passed at weaning time and lower liveweight gain than the Amprolium-medicated kids. In the Eimeria superinfected kids the trichostrongyle infection caused a tendency to result in chronic coccidial infections. Further, these animals had higher numbers of nematode eggs in their faeces, lower dressed weights on slaughter and inferior meat quality. PMID- 8447061 TI - Sarcocystis fusiformis: some protein metabolic enzymes in various fractions of sarcocysts of buffalo (Bubalus bubalis). AB - An investigation on the relative presence of some protein metabolic enzymes, namely aspartate aminotransferase (AST), alanine aminotransferase (ALT), NAD+ and NADP+ dependent glutamate dehydrogenase (GLDH) and arginase in cyst wall (CW), cyst fluid (CF) and zoite (ZT) fractions of the sarcocysts of Sarcocystis fusiformis in the oesophageal muscles of Indian water buffalo was carried out. Both the transaminases were present in all the fractions of the cyst, although in variable amounts. There was a higher level of AST activity than of ALT activity. AST activity was the highest in ZT, whereas ALT activity was at a maximum in the CF fraction. The levels of activity of NAD+ and NADP+ dependent GLDH and arginase remained beyond detectable limits. The study revealed that the intermediates of carbohydrate metabolism are linked to protein metabolism by transaminases. The possibility of concomitant removal of ammonia and its subsequent incorporation into the urea cycle is ruled out in this parasitic protozoan. PMID- 8447062 TI - Natural besnoitiosis in a rabbit. AB - An adult female rabbit was submitted for necropsy after sudden death. Pneumonia and nephritis were diagnosed by gross examination. On histological examination. Besnoitia cysts were seen in the pulmonary interalveolar tissue. The Besnoitia cysts were morphologically normal in appearance, measured 127 to 185 microns in diameter and provoked mild mononuclear inflammatory reaction. To the best of our knowledge there has been no previous report of natural besnoitiosis in rabbits. PMID- 8447063 TI - The effect of halofuginone lactate on experimental Cryptosporidium parvum infections in calves. AB - The chemoprophylactic effects of halofuginone lactate were tested against calf experimental cryptosporidiosis. Twenty 2-day-old calves, divided into four groups, were orally inoculated with 1 x 10(6) oocysts of Cryptosporidium parvum. The infected control group was unmedicated whereas the three other groups were medicated with the drug at 30, 60 and 120 micrograms kg-1 day-1, respectively, for 7 days, from Day (D) 2 to D8 post-inoculation (D 0 was inoculation day). The calves were weighed twice weekly and disease development and drug efficacy were assessed daily from D0 to D30 from consistency of feces, shedding of oocysts and mortality. Experimental C. parvum infection caused a severe clinical disease with profuse watery diarrhea, high oocyst shedding and mortality (3 out of 5) in the unmedicated group. The results clearly demonstrated the efficacy of halofuginone lactate in reducing the severity of clinical cryptosporidiosis. This efficacy was dose-dependent. The lowest dose (30 micrograms kg-1 day-1) was not able to prevent clinical disease and mortality (3 out of 5). No clinical signs were observed with the 60 and 120 micrograms kg-1 day-1 doses, but the animals shed oocysts after drug withdrawal. This shedding was more delayed the higher the dose of drug administered, but the delayed shedding had no effect on the growth of the animals. PMID- 8447064 TI - Prevalence of Cryptosporidium oocysts in livestock in Trinidad and Tobago. AB - Faecal samples from 683 diarrhoeic and non-diarrhoeic piglets, calves, lambs and goat kids were examined for Cryptosporidium oocysts. The prevalence of infection in piglets and lambs was 19.6% and 20%, respectively, and these rates were significantly higher than those detected in calves (8.7%). Amongst the four animal species studied, the detection rates were higher in diarrhoeic than in non diarrhoeic animals and in animals under extensive and semi-intensive husbandry systems. However, these differences were not statistically significant. PMID- 8447065 TI - Efficacy of semduramicin and salinomycin against different stages of Eimeria tenella and E. acervulina in the chicken. AB - The efficacy of a new ionophore, semduramicin, was compared with salinomycin in a series of in ovo and in vivo trials. Semduramicin was more efficacious than salinomycin against Eimeria tenella sporozoites as judged by oocyst production in embryonated eggs. When the two drugs were given in ovo at 93 h post inoculation (PI), both drugs exerted some effect against late schizogonous stages of E. tenella. In three battery studies, semduramicin (25 ppm) and salinomycin (60 and 66 ppm) were tested against E. tenella and E. acervulina. Medicated feed was withdrawn at 24-h intervals PI to study the stage of action of the anticoccidials. In E. tenella infected chickens, both anticoccidials exerted their maximum effect on weight gain and feed:gain ratio through the first 72 h PI. Semduramicin was more effective than salinomycin in controlling E. tenella lesions and coccidiosis mortality. With E. acervulina, both drugs acted similarly on early life cycle stages and no improvement in performance was recorded when medicated feed was given for longer than 72 h. Semduramicin was more effective than salinomycin in controlling E. acervulina lesions. PMID- 8447066 TI - Comparison of antibody- and antigen-detection enzyme immunoassays for the diagnosis of Trypanosoma evansi infections in camels. AB - A total of 183 camels from Kenya were examined for circulating trypanosomal antigens by four methods: (1) a monoclonal antigen-detection enzyme-linked immunosorbent assay (Ag-ELISA) and circulating anti-trypanosomal antibodies; (2) antibody-detection enzyme-linked immunosorbent assay (Ab-ELISA); (3) buffy-coat examination (BCE); (4) mouse subinoculation (MI). Thirty-seven camels (20%) were parasite-positive by BCE and 60 camels (33%) were parasite-positive by MI. Sixty three camels (34%) tested positive on Ag-ELISA. Of the 24 camels which could not be detected by BCE, Ag-ELISA detected 18 (75%). Ab-ELISA detected 90 (49%) positive camels. Of all the parasite-positive camels (61), Ag-ELISA detected 93% and Ab-ELISA 95%. Based on the results of 55 camels, there was a significant statistical difference (P < 0.0001) in Ag-ELISA optical density (OD) values (of either serum or plasma antigen analysis) between parasite-positive and parasite negative camels. No significant difference was observed in Ab-ELISA OD values between parasite-positive and parasite-negative camels. Diagnosis of T. evansi infection in camels by the use of Ag-ELISA alone or in combination with BCE could therefore be a more preferred approach in assessing patient infection than the use of Ab-ELISA. PMID- 8447067 TI - Measurement of trypanotolerance criteria and their effect on reproductive performance of N'Dama cattle. AB - One thousand and twenty-eight cow-year records were available from 260 N'Dama cows each having at least 2 years of monthly matching health and performance data over a 5-year period under a medium natural tsetse challenge in Gabon. Four hundred and fifty-eight calf/dam pairs were also available where the calf had been reared to weaning, both had monthly matching records and each cow had weaned at least two calves. Evaluations were carried out on effects of, and linkages between, environmental and stress factors, number and species of trypanosome infections, curative drug treatments given, anaemia measured by packed red cell volume (PCV), and performance measured by calf weaning weight, cow calving rate and cow weight change over the lactation period. Major findings were that over the period from calf birth to weaning, while calves and their dams grazing together had similar numbers of trypanosome infections detected, the Trypanosoma vivax: T. congolense ratios were very different: 1:0.7 in calves; 1:2.8 in cows. This indicated that some ability to control the development of parasitaemia following T. vivax infection might be being acquired, from weaning onwards. In cows, relationships between lowest PCV recorded and curative drug treatments given suggested that between 20 and 32% of trypanosome-infected cows were not being identified by the buffy coat parasitological diagnostic technique. The high level of curative treatment given (to 13.7% of cows over the calendar year, and to 40% of calves from birth to weaning) will have tended to reduce the variance and linkages between aspects of infection and PCV values, especially in calves. In calves, the influence of trypanosome infections, in both calf and dam, on their respective PCV values and hence on calf weaning weight was apparent. There was a 0.91 +/- 0.40 kg increase in calf weaning weight for each 1% increase in calf average PCV, and a 0.95 +/- 0.39 kg increase for each 1% increase in cow average PCV. In cows, there was a similar pathway of influence of T. congolense infection through the PCV values to calving rate--not significant with T. vivax infection. There was a 3.3 +/- 0.65% increase in calving rate for each 1% increase in average PCV. Repeatabilities of performance traits were in the normal range. Repeatabilities of numbers of trypanosome infections detected by the buffy coat technique were too low to have any practical significance. Repeatability of average PCV at 0.40 +/- 0.03 could allow PCV when infected to be used as one criterion of trypanotolerance. PMID- 8447068 TI - Differentiation of seven Eimeria species by random amplified polymorphic DNA. AB - Eimeria species were differentiated by the polymerase chain reaction using random amplified polymorphic DNA. Seven arbitrary primers ranging in length from ten to 20 nucleotides were used with DNA of seven species of eimerian oocysts to generate unique DNA fingerprints. DNA fragments ranging from 200 to 2200 base pairs (bp) were synthesized in the different reactions. Species-specific DNA fragment mobility patterns were observed in most cases. In several assays, multiple DNA fragments were synthesized and, in the majority of assays conducted, the Eimeria species could be easily differentiated. Only six of the 49 assays performed failed to generate DNA fragments. PMID- 8447069 TI - Ultrastructural study of Cryptosporidium development in Madin-Darby canine kidney cells. AB - Transmission electron microscope studies have been made into phases of the life cycle of a bovine isolate of Cryptosporidium cultured in vitro on Madin-Darby canine kidney cells. The cytoplasm of parasitized cells was noticeably altered, including marked vacuolization and the appearance of membrane structures close to the developing parasites. These changes suggest that the protozoan may release cytopathogenic factors. PMID- 8447070 TI - The ecology of Haemonchus contortus in a winter rainfall region in Australia: the development of eggs to infective larvae. AB - The seasonal pattern of development of Haemonchus contortus eggs to infective larvae was investigated on the south coast of Western Australia. Sheep faeces containing H. contortus eggs were deposited on pasture plots at intervals over a 3-year period, and pasture grass and faeces were sampled periodically for infective larvae (L3). The maximum recoveries occurred in late autumn and in late spring, when adequate moisture coincided with warm temperatures. Larval development was low and sporadic over the hot and dry summer period, and depressed during winter, although most egg depositions in winter yielded L3 at some time. The proportion of L3 recovered was related to temperature and moisture parameters, and the major constraint appeared to be the availability of moisture at pasture level. The best indicator of the suitability of conditions for the development of H. contortus was the proportion of green pasture material present, based on a visual assessment. PMID- 8447071 TI - The ecology of Haemonchus contortus in a winter rainfall climate in Australia: the survival of infective larvae on pasture. AB - At sites near Albany, on the south coast of Western Australia, sheep faecal pellets containing either eggs or infective larvae (L3) of Haemonchus contortus were deposited onto natural pasture plots at intervals over 3 years. Faecal and pasture samples were collected periodically and processed to detect L3. On annual pasture plots, L3 were recovered for from 10 to over 20 weeks from depositions made between autumn and early spring, at which time temperatures were mild or low, rainfall was frequent and the pasture was visibly green. During the hot and dry summer, when the pasture was completely dry, L3 often failed to develop or were recovered on only a single occasion, and the mean larval survival period on positive plots was less than 5 weeks. In contrast, L3 deposited on green perennial pasture plots in summer were recovered for up to 4 months in faecal pellets and on pasture. The longest periods of larval survival were associated with the lowest temperature and highest rainfall recordings, and with the greatest quantity of green plant material in the pasture. It is suggested that the poor survival of L3 during the dry summer period could be used in a strategic treatment programme to interrupt the transmission cycle of H. contortus in winter rainfall climates. However, areas of green pasture which persist in summer may provide a sufficiently moist microclimate to permit the survival of H. contortus L3 despite otherwise unfavourable environmental conditions. PMID- 8447072 TI - Isolation and partial characterisation of an immunogen from the mite, Psoroptes cuniculi. AB - The immunological reactions of Psoroptes cuniculi protein components with antigen specific rabbit antisera and with six plant lectins are described. In immunoblotting, the antisera from rabbits heavily and mildly infested with Psoroptes cuniculi recognized from two to five protein components. Affino blotting analysis showed that eight mite components were glycoproteins with different types of glycan structures. The immunogenic antigen was isolated by both immunoaffinity chromatography and identified by crossed immunoelectrophoresis. It was a glycoprotein with a relative molecular mass of 48 kDa and with complex or high mannose type of oligosaccharides. PMID- 8447073 TI - Unidentified Toxoplasma-like tissue cysts in the brains of three cats. AB - Tissue cysts of an unidentified Toxoplasma-like parasite were found in three of 103 cats that were diagnosed histologically with toxoplasmosis-like illness at the Angell Memorial Animal Hospital, Boston, MA, between 1952 and 1991. Tissue cysts in these three cats were confined to the brain and two cats had concurrent lymphoid disorders. The tissue cysts of the unidentified parasite were about twice the size of Toxoplasma gondii tissue cysts. PMID- 8447074 TI - Visceral toxoplasmosis in dogs from Brazil. AB - Toxoplasma gondii was identified in tissues of two dogs (3 and 10 months of age) from Brazil. Primary lesions consisted of necrotizing intestinal myositis associated with numerous tachyzoites. Parasites in tissues reacted with anti-T. gondii serum but not with Neospora caninum serum. PMID- 8447075 TI - Trypanozoon-like epimastigotes in the larvae of Cephalopina titillator (Diptera: Oestridae) infesting camels (Camelus dromedarius) infected with Trypanosoma evansi. PMID- 8447076 TI - Parasitic gastritis in a llama (Lama glama) associated with inhibited larval Teladorsagia spp. (Nematoda: Trichostrongyloidea). AB - A 7-year-old female llama was experimentally infected with 500 Fasciola hepatica metacercariae then turned out onto pasture also grazed by domestic sheep. The llama was necropsied approximately 22 weeks post infection. Routine examination of the gastrointestinal tract revealed diffusely coalescing, umbilicated nodules covering the caudal one-fifth of the third stomach compartment. Microscopically, the mucosa was irregularly thickened. Numerous nematode larvae were present in glandular lumens, often extending to the base of the glands. Where nematodes were most numerous, decreased numbers of parietal cells, attenuation of glandular epithelium and increased collagen within the lamina propria were evident. Of a total of 6510 adult nematodes in the third stomach compartment, 51% were Teladorsagia spp., 47% were Trichostrongylus axei, and 2% were Camelostrongylus mentulatus. Except for C. mentulatus, three sheep that had grazed with the llama and were necropsied at approximately the same time, harbored the same nematode species. The total number of larvae in the llama was 56,710, with more than 97% being ostertagiine early fourth-stage larvae. Ostertagiine larvae were also present in the sheep. Based on the composition of the adult populations in the llama and sheep, the larvae were considered to be species of Teladorsagia. Additionally, the larger numbers of early fourth-stage larvae indicated that the development of Teladorsagia spp. in the llama is inhibited. PMID- 8447077 TI - Clonal diversity among strains of Escherichia coli incriminated in turkey colisepticemia. AB - The extent of genetic differentiation among 80 Escherichia coli isolates collected from turkeys with acute colisepticemia was assessed based on allelic variation at 20 enzyme-encoding loci detected by multilocus enzyme electrophoresis. Isolates were polymorphic at 17 loci and were classified into 32 multilocus genotypes, delineating clones, that differed on average at 36% of the loci. In the total sample, 29 (36%) of the isolates belonged to one of two closely related clones, differing only in a single electromorph, and 11 of these isolates were serogroup O78. Most isolates fell into one of 4 genetically distinct clusters of strains. Three of these clusters represent E. coli clone complexes that have been previously identified in avian diseases and a fourth cluster which is specific to colisepticemia in turkeys. Most (73%) isolates produced aerobactin, whereas none produced hemolysins. Assays for detecting K1 capsules, including the use of polyclonal antisera, monoclonal antibodies, and K1 specific bacteriophages, gave variable results, but showed that overall 18% of the strains from colisepticemia were K1 encapsulated with most of the K1+ isolates found in one clone cluster. The results show that many cases of colisepticemia in turkey flocks are caused by a small number of pathogenic clones representing at least three distinct clone complexes. PMID- 8447078 TI - Development of a single dilution ELISA to detect antibody to Dermatophilus congolensis in goat and cattle sera. AB - A solid phase immunosorbent assay to detect antibodies to Dermatophilus congolensis in ruminant sera was developed to be used as a single dilution ELISA in large epidemiological surveys. Optimal conditions for the test are described. The use of blocking proteins to reduce non specific binding was necessary. Non fat dry cow milk and fetal calf serum were the only two efficient blocking agents out of six tested. Comparison of 4 antigenic fractions obtained after sonication and differential centrifugations of D. congolensis cultures showed that cell-wall (CW) or membrane (M) enriched preparations were more specific than a crude extract (CR) or a soluble (S) antigen. Whole spores and filaments performed poorly as antigens. The best sensitivity and specificity of the ELISA were obtained when the cut-off point of positivity was fixed at mean absorbance of negative sera + 2.58 sd. The specificity was then 97.6% either with M or CR antigen. The sensitivity was improved from 93.4% with CR to 98.2% with M antigen. Threshold values for a positive test varied between the 3 geographical areas tested. CW and M were also the most efficient antigens for discerning between serotypes of D. congolensis. The precision of the test was evaluated with CR antigen and expressed in residual expressed in residual coefficient of variation (CV). The precision was CV = 5.1% when each serum was titrated in duplicate and the antibody levels were expressed in absorbances. The expression of antibody levels in arbitrary standard units estimated from calibration curves reduced the precision (CV = 13.8%). Several methods were tested to decrease between plate variability but these did not greatly improve the reproducibility since it was shown that the main source of variation was within the plate. PMID- 8447079 TI - Blood T6-lymphocyte antigen levels as a poor resistance marker in ovine dermatophilosis. AB - Merino ewes lambs from a flock expected to have a high prevalence of dermatophilosis were examined for lesions at marking, weaning and prior to first shearing. Blood was collected at marking and prior to shearing to enable quantification of T6-lymphocyte antigen levels in peripheral blood mononuclear cells (PBM) using monoclonal antibody SBU-T6 20-27. A group of the lambs that had persistent and/or severe dermatophilosis had significantly lower (P < 0.05) mean levels of T6-lymphocyte staining in PBM than those with minimal or no dermatophilosis in blood samples collected prior to shearing. However, the wide variability of this parameter in resistant and susceptible lambs indicated that this would not be a satisfactory procedure to rank sheep for resistance to dermatophilosis. PMID- 8447080 TI - Comparison of the in vitro adhesion of K88, K99, F41 and P987 positive Escherichia coli to intestinal villi of 4- to 5-week-old pigs. AB - The adhesion of K88ab, K88ac, K88ad, P987, K99, F41 and K99/F41 positive Escherichia coli strains to duodenal, jejunal and ileal villi was studied using an in vitro adhesion assay. The villi were harvested from 4- to 5-week-old pigs. The K88+ strains adhered in large numbers (42 +/- 5 to 81 +/- 4 E. coli/250 microns villous length) to the villi from most pigs and in low to moderate numbers (5 +/- 2 to 24 +/- 7 E. coli/250 microns villous length) or not to villi of some pigs. The K99+ and F41+ strains either adhered in low numbers (1 +/- 1 to 11 +/- 2 E. coli/250 microns villous length) or did not adhere, whereas the P987+ and K99/F41+ strains always adhered in low to moderate numbers (2 +/- 1 to 26 +/- 2 E. coli/250 microns villous length). The number of bacteria adhering to the villi was the highest for the K88ab+ and K88ac+ strains (55 +/- 5 to 81 +/- 4 E. coli/250 microns villous length) and decreasing in the following order: K88ad > P987 > K99/F41 > K99 > F41 (= 1 +/- 1 to 4 +/- 1 E. coli/250 microns villous length). There was no difference in the adhesion of the villi of the different small intestinal segments for the P987+ and F41+ strains. The K99+ strains adhered significantly more to the villi of the caudal half of the small intestine, the K99/F41+ strain to jejunal and ileal and the K88+ strains to jejunal villi in comparison to duodenal ones. PMID- 8447081 TI - Discrimination between virulent and nonvirulent Streptococcus suis type 2 strains by enzyme-linked immunosorbent assay. AB - Discrimination between virulent and nonvirulent strains of Streptococcus suis type 2 will allow proper diagnosis of diseased pigs and the identification of carrier pigs. To discriminate between virulent and nonvirulent strains, we developed two double antibody sandwich (DAS) enzyme-linked immunosorbent assays (ELISA) using specific monoclonal antibodies directed against two virulence markers of S. suis type 2. One mAb was directed against the 136-kilodalton (kDa) cell-wall-associated protein, designated muramidase-released-protein (MRP). The other mAb was directed against a 110-kDa extracellular protein, provisionally called extracellular factor (EF). We examined 179 strains of S. suis serotype 2, 22 strains of S. suis serotypes 1 to 22, 22 other streptococci, 20 other bacterial strains, and one yeast. The ELISA results were almost identical with western blot analysis of these strains. Visual readings of the two DAS-ELISAs were enough to discriminate accurately between the three phenotypes of S. suis type 2. We concluded that the two DAS-ELISAs are reliable, rapid, and simple assays to identify virulent strains of S. suis type 2. PMID- 8447082 TI - Comparative use of DNA probes for Mycobacterium avium and Mycobacterium intracellulare and serotyping for identification and characterization of animal isolates of the M. avium complex. AB - Commercially available DNA probes for the Mycobacterium avium complex (MAC) were compared with conventional identification and serotyping of animal isolates of MAC. DNA hybridization of 44 strains of mycobacteria showed a test specificity of 100% and sensitivity of 100%. Hybridization of 12 serotype strains showed that serotypes 1-6 and 8-11 hybridized with the M. avium probe and serotypes 7 and 14 hybridized with the M. intracellulare probe. All of the 42 bovine and porcine isolates of MAC consisting of serotypes 1-6 and 8-10 hybridized only with the M. avium probe. Two strains originally identified as MAC by biochemical tests turned out to be negative in the hybridization test and were identified as rapid growers in gas chromatography analysis of fatty acids. This study furthermore indicates that MAC infections in animals in Norway are mainly caused by M. avium probe positive strains. PMID- 8447083 TI - Chromosomal DNA probes for the identification of Bacteroides tectum and Bacteroides fragilis from the oral cavity of cats. AB - A dot-blot hybridisation assay using high molecular weight DNA as whole chromosomal probes was used to differentiate Bacteroides tectum from Bacteroides fragilis. 32P-labelled probes were compared with digoxigenin (DIG)-labelled probes. The whole chromosomal probes were specific--differentiating B. tectum from B. fragilis and both from a variety of other species (including other members of the genera Bacteroides, Fusobacterium, Eubacterium, and Prevotella) found in normal and abnormal mouths of cats and horses. However, even at very high stringencies, B. tectum homology groups I, II and III were not distinguishable from one another using either 32P-labelled or DIG-labelled probes. Thus, DIG-labelled whole chromosome probes directed against cellular DNA released directly onto nitrocellulose membranes is considered a useful method for diagnostic veterinary laboratories wishing to identify B. tectum and distinguish it from B. fragilis and other oral anaerobic flora of cats. PMID- 8447084 TI - Canine IgA glomerulonephropathy. AB - Three young intact male dogs housed together in a canine blood donor facility developed immune complex glomerulonephropathy within 2 years of each other. All three had membranoproliferative glomerulonephritis with varying clinical presentation and progression. Two dogs had subendothelial, and one dog subepithelial, electron microscopic dense deposits. Immunoperoxidase staining indicated that the primary antibody involved in the glomerular disease of these three dogs was IgA. The nature of the electron dense deposits was further studied by eluting and identifying immunoglobulin from affected kidneys of one dog. The primary antibody identified had a molecular weight greater than 300,000 Da and was determined to be IgA. Although IgA glomerulonephropathy is a common cause of glomerular disease in humans, this study represents the first documentation of the clinical syndrome of IgA glomerulonephropathy in the dog. PMID- 8447085 TI - Recombinant human interleukin 2 induces proliferation and immunoglobulin secretion by bovine B-cells: tissue differences and preferential enhancement of immunoglobulin A. AB - Recombinant human interleukin 2 (rhIL2) was found to have activity on bovine B cells in vitro, inducing both their proliferation and differentiation into immunoglobulin secreting cells. Only low and medium density (activated) B-cells were responsive; high density (resting) B-cells did not respond to rhIL2. Proliferative responses by unfractionated and purified B-cell populations were similar for all tissues tested. In contrast, immunoglobulin secretion was stimulated to a greater degree in prescapular lymph node (PSLN) and bronchial lymph node (BLN) cells than in mesenteric lymph node (MLN) cells and splenic lymphocytes on culture with IL2. All isotypes were stimulated equally in the case of PSLN, BLN, and splenic lymphocytes. However, culture of unfractionated MLN lymphocytes with IL2 resulted in enhanced secretion of IgA relative to the other isotypes. Removal of T-cells and accessory cells from the MLN lymphocyte preparation resulted in this effect being lost. PMID- 8447086 TI - Comparison of Brucella abortus antigen preparations for in vitro stimulation of immune bovine T-lymphocyte cell lines. AB - Three Brucella abortus antigen preparations were tested for stimulatory activity with immune bovine T-lymphocyte cell lines in vitro. A total of 32 polyclonal T lymphocyte cell lines were derived from two steers each from four immunization groups: (1) B. abortus Strain 19 (S19) alone, (2) heat-killed B. abortus whole bacterial cells (HKC) alone, (3) S19 with recombinant human interleukin 2 (rHuIL 2), (4) HKC with rHuIL-2. Peripheral blood mononuclear cells were isolated at 2 and 9 weeks post immunization and cultured in vitro with either HKC antigen or B. abortus soluble antigen (BASA) with recombinant bovine interleukin 2 (rBoIL-2) to initiate four cell lines per steer. Sixteen of the resulting T-lymphocyte cell lines (from the S19 and S19+IL-2 groups) were tested through indirect immunofluorescence for expression of cell surface markers CD2, CD4, CD6, CD8, major histocompatibility complex (MHC) Class II molecules and a marker expressed on a subset of helper T-lymphocytes (Th) as well as sIgM, CD1 and a MHC Class II+ monocyte/macrophage marker. The T-lymphocyte cell lines were used to evaluate antigen-induced lymphoproliferative (LP) responses in a titration assay with HKC, BASA and gamma-irradiated B. abortus (gamma BA) antigens. The results indicate that most of the cells in many of the cell lines were typical activated T lymphocytes as determined by surface marker expression and included cells positive for all T-lymphocyte markers tested. The cell lines contained no B lymphocytes or mononuclear phagocytes. However, two cell lines contained significant populations (> 80%) of CD2-, CD4-, CD6-, CD8- cells that were both responsive to exogenous rBoIL-2 and were capable of exhibiting antigen-induced LP responses. In 22 of the 32 cell lines tested, gamma BA was superior to HKC at nearly every concentration tested in stimulating LP responses. This observation was independent of the immunization used to prime the T-lymphocytes in vivo. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed proteins with relative molecular masses common to all three antigen preparations as well as significant (P < 0.05) quantitative and qualitative differences in individual proteins between HKC and gamma BA. Together, the results suggest gamma BA may provide an in vitro antigenic stimulus which is deficient in HKC. PMID- 8447087 TI - Binding of dog immunoglobulins G, A, M, and E to concanavalin A. AB - The binding of dog immunoglobulins G, A, M and E to concanavalin A (Con A) has been investigated. A passive cutaneous anaphylaxis test was used for measurement of dog IgE, and enzyme-linked immunosorbent assay was used for measurement of dog IgG, IgA and IgM. After the dog serum fraction was applied to a Con A-Sepharose column, sequential elution with different buffers was performed; 100% of IgE and IgM, 60% of IgG and 58% of IgA bound to the Con A-Sepharose. IgE was eluted by mannose, methylglucose, and methylmannoside. IgG was eluted by glucose, mannose, methylglucose, and methylmannoside. IgA and IgM were eluted by methylmannoside only. This provides a useful technique in the purification of dog immunoglobulins, especially dog IgE. PMID- 8447088 TI - Structure and evolution of the polymorphic photopigment gene of the marmoset. AB - The marmoset Callithrix jacchus jacchus, is typical of a New World monkey in exhibiting a polymorphism of photopigments in the middlewave to longwave (535-565 nm) region of the spectrum. The single X-linked opsin gene that encodes the protein component of these pigments is present in three allelic forms producing, in marmosets, pigments with maximum sensitivities at about 543, 556 and 563 nm. All male monkeys are dichromats, whereas females may be either dichromats or trichromats. A cDNA sequence corresponding to the 563 form of this gene is reported, together with partial genomic DNA sequences of exons 2, 3, 4 and 5 of all three alleles. The origin of these sequences and their divergence from the middlewave- and longwave-sensitive pigments of man is discussed from both a functional and an evolutionary standpoint. PMID- 8447089 TI - Synthesis of 3-hydroxyretinal in the cytosol of the butterfly compound eye. AB - The metabolism of 3-hydroxyretinoids in the cytosol of the compound eyes of a species of butterfly, Papilio xuthus, was investigated. The cytosol was found to contain 25-30% of the total 3-hydroxyretinal and 70-82% of the total 3 hydroxyretinol in the eye. These percentages of 3-hydroxyretinoids in the cytosol were found to be constant regardless of whether the eyes are light-adapted or dark-adapted. 3-Hydroxyretinal can be newly synthesized in the cytosol of light adapted eyes. Blue light specifically increases the amount of 11-cis and all trans 3-hydroxyretinal ca 2.5 and 1.8 times respectively, compared to pre irradiation. When 3-hydroxyretinal was synthesized, 3-hydroxyretinol was decreased or disappeared in the cytosol. When retinol (non-native chemical) was added to the cytosol, it was converted into retinal. This result indicates that an oxidative system exists in the compound eye which can convert 3-hydroxyretinol to 3-hydroxyretinal. PMID- 8447090 TI - Color appearance of filled-in backgrounds affects hue cancellation, but not detection thresholds. AB - A long-wavelength background can affect the appearance of an increment of light superimposed upon it in two ways. It can change the visual system's sensitivity to the increment, and it can change the appearance of the increment by directly adding redness to it. Through selective retinal-image stabilization, we evoked the filling-in phenomenon to change the appearance of 640- and 575-nm backgrounds. Either of these backgrounds could be made to appear red or yellow, depending upon whether it was viewed under stabilized or unstabilized conditions. When the appearance of the 640-nm background was altered by filling-in to appear less red, test probes superimposed upon it required less 540-nm component to achieve an equilibrium hue. Increment thresholds measured on the 640- and 575-nm backgrounds, however, did not change with the appearance of the backgrounds. PMID- 8447091 TI - Contour integration by the human visual system: evidence for a local "association field". AB - The Gestalt law of "good continuation" has been used to describe a variety of phenomena demonstrating the importance of continuity in human perception. In this study, we consider how continuity may be represented by a visual system that filters spatial data using arrays of cells selective for orientation and spatial frequency. Many structures (e.g. fractal contours) show a form of redundancy which is well represented by the continuity of features as they vary across space and frequency. We suggest that it is possible to take advantage of the redundancy in continuous, but non-aligned features by associating the outputs of filters with similar tuning. Five experiments were performed, to determine the rules that govern the perception of continuity. Observers were presented with arrays of oriented, band-pass elements (Gabor patches) in which a subset of the elements was aligned along a "jagged" path. Using a forced-choice procedure, observers were found to be capable of identifying the path within a field of randomly oriented elements even when the spacing between the elements was considerably larger than the size of any of the individual elements. Furthermore, when the elements were oriented at angles up to +/- 60 deg relative to one another, the path was reliably identified. Alignment of the elements along the path was found to play a large role in the ability to detect the path. Small variations in the alignment or aligning the elements orthogonally (i.e. "side-to-side" as opposed to "end-to-end") significantly reduced the observer's ability to detect the presence of a path. The results are discussed in terms of an "association field" which integrates information across neighboring filters tuned to similar orientations. We suggest that some of the processes involved in texture segregation may have a similar explanation. PMID- 8447092 TI - Rod-cone interaction in form detection. AB - Using a Wright colorimeter, absolute threshold, absolute form threshold and specific form threshold were measured during long-term dark adaptation in the extrafoveal retina. The specific form threshold was found to fall markedly at about the cone-rod break but thereafter rose steeply. Furthermore, during the rod phase of the dark adaptation the form percept of the small, slender rectangular test field changed qualitatively from a line or rectangle to a circular field at all mesopic intensities. The results indicate that light signals from rods may both facilitate and suppress cone-mediated information about form, and that the rod system may completely dominate the perception of form several log units above the absolute dark-adapted cone threshold when the eye is dark adapted. PMID- 8447093 TI - Smooth pursuit initiation in young and elderly subjects. AB - Smooth pursuit initiation to step-ramp stimuli was investigated in normal subjects, young and elderly. Older subjects had significant reductions in initial pursuit acceleration before saccades, and in post-saccadic and peak pursuit velocities. Aging impairs the open-loop performance of the pursuit system, possibly by decreasing sensitivity to retinal image motion or by limiting the conversion of visual motion signals into commands for smooth pursuit. Lower open loop pursuit gain degrades steady-state, closed-loop smooth pursuit in senescence. Our elderly subjects also made less accurate saccades to moving targets, implying defective use of visual motion information by the saccadic system. PMID- 8447094 TI - Motion perception during saccades. AB - Although the retinal image is displaced by each saccade performed we do not perceive the visual environment moving concordant with the saccades. In this study experiments were designed in which additional movement of most of the visual scene was applied during saccades. The subjects perceived the intrasaccadic movement after the saccade. The perceived speed of this movement was decreased and the threshold amplitude was increased compared to perception during fixation. The intrasaccadic movement perception was based on a novel aftereffect of motion perception. The velocity of retinal slip did not affect the threshold. If the retinal slip speed during saccades was temporally reduced by an intrasaccadic movement parallel to the saccade, the threshold amplitude was identical to the threshold amplitude obtained by intrasaccadic movement opposite to the saccade increasing retinal slip speed. Horizontal intrasaccadic movements were detected at lower thresholds than vertical movements independent of saccade direction. In addition, the thresholds were not effected by the saccade amplitude suggesting that neither speed, duration, nor direction of eye movement related retinal slip affects the amount of suppression. Our results suggest that saccadic suppression is related to delayed central processing of retinal information during saccades. This processing does not involve saccade parameters such as direction and amplitude. PMID- 8447095 TI - Texture segregation based on two-dimensional relative phase differences in composite sine-wave grating patterns. AB - Experiments examined the visual processing of relative phase relations between differently oriented components of a textured pattern. The textures were a super position of three 1.3 c/deg sine-wave gratings rotated 60 deg relative to one another. Global orientation and relative phase were varied. Subjects rated the segregation of pairs of textures presented in a figure/ground configuration at 10 deg retinal eccentricity. Both orientation and phase differences were used in making ratings. It was not simply the difference in relative phase that mattered. The results also depended on the values of the relative two-dimensional (2-D) phases in figure and ground. Mirror-image texture pairs (which may have a large relative phase difference) segregated poorly compared to other pairs with similar phase differences. This suggests that the peripheral visual system does not completely encode 2-D relative phase. Secondary issues include spatial frequency effects, the relevance of figure/ground borders, and better performance in the lower visual field. PMID- 8447096 TI - Red-green color discrimination in peripheral vision. AB - Color discrimination thresholds were measured for four colors from the red-green portion of the visible spectrum. Thresholds were measured for a stimulus field 1.5 deg in diameter in the fovea and at three locations on the nasal retina (eccentricities of 5, 20 and 40 deg). Outside the fovea threshold increased exponentially with eccentricity and the slope of the function was similar for all four standard colors. Peripheral thresholds were adequately described by an equation developed for foveal red-green thresholds by Boynton and Kambe [(1980) Color Research and Applications, 5, 13-23] and also by a modified form of this equation containing a rod term. Differences between foveal and peripheral thresholds were characterized by changes in two coefficients in the equations. The CIELUV color difference equation also provided a reasonably good description of peripheral thresholds. PMID- 8447097 TI - Visibility of elliptical Gaussian blobs. AB - Contrast detection thresholds for horizontally and vertically oriented elliptical stimuli with a 2D-Gaussian luminance profile in space and a Gaussian envelope in time were measured as a function of their spatial scale parameters for two different presentation times. For slowly varying stimuli, threshold is independent of stimulus size whenever the minor axis of the stimuli exceeds 10-20 min of arc. If the presentation time is shorter, the occurrence of size invariance also depends on the area of the stimulus. In general no significant dependence of the threshold on stimulus orientation is found. Where size invariance occurs it holds that: (1) the threshold is determined by the ratio between the major and the minor axis of the stimulus; (2) the threshold is highest for circular blobs; (3) for greatly elongated blobs the threshold varies as a power of the ratio. For slowly varying stimuli, this power equals -1/2; if the stimulus varies rapidly in time, thresholds depend much less on the ratio, unless the minor axis is small. The results are predicted by a multi-layer receptive field model in which the detection units resemble circular symmetric X type cells, and in which the total response is obtained after Pythagorean summation of the contributions of the individual units. Probability summation cannot explain our results. PMID- 8447098 TI - Spatiotemporal contrast sensitivity of early vision. AB - Based on the spatial and temporal statistics of natural images, a theory is developed that specifies spatiotemporal filters that maximize the flow of information through noisy channels of limited dynamic range. Sensitivities resulting from these spatiotemporal filters are very similar to the human spatiotemporal contrast sensitivity, including the dependence on ambient light intensity. The theory predicts several psychophysical laws: Ferry-Porter's law, the de Vries-Rose law, Weber's law, Bloch's law, Ricco's law, and Piper's law. PMID- 8447099 TI - Genetic basis of polymorphism in the color vision of platyrrhine monkeys. AB - It was earlier proposed that the polymorphism of color vision observed in some neotropical monkeys could be accounted for by assuming that these animals have only a single photopigment gene locus on the X-chromosome. Three kinds of evidence have been added to existing data sets in an effort to evaluate the adequacy of the single locus model: (1) photopigment complements of squirrel monkeys (Saimiri sciureus) have been determined using electroretinogram flicker photometry; (2) photopigment pedigrees have been established for several families of squirrel monkey; (3) X-chromosome pigment genes obtained from six dichromatic monkeys (three squirrel monkeys; three tamarins--Saguinus fuscicollis) have been examined to search for sequence polymorphisms at those gene loci believed crucial for spectral tuning. All of these results are in accord with the idea that some species of platyrrhine primate have only a single type of photopigment gene on the X-chromosome. PMID- 8447100 TI - Spatial and chromatic interactions in the human pattern electroretinogram. AB - The spectral sensitivity and the spatial selectivity was studied both psychophysically and electroretinographically using the pattern onset-offset paradigm. All measurements were made under intensive yellow adaptation. The spectral sensitivity functions of both measures were in close agreement. They showed a peak at 460 nm (blue-sensitive mechanism) and a shoulder around 550 nm (red-green-sensitive mechanism). The luminance curves of the pattern onset ERG obtained with long wavelengths had a steeper slope and reached larger amplitudes than those obtained with short wavelengths. In addition the response-peak times were longer with short wavelengths. When the spatial frequency of the pattern was varied the 460 nm-onset responses showed very little or no spatial tuning and long peak times (around 60 msec). This was ascribed to the contribution from only one type of ganglion cell, namely the blue-yellow opponent receptive fields lacking a center-surround organization. The 550 nm-onset responses showed a clear spatial tuning (4 c/deg) and an increase in peak time (40-50 msec) with increasing spatial frequency (0.26-9.2 c/deg). This was ascribed to different types of receptive fields having a center-surround structure. PMID- 8447101 TI - Spectral transmission and short-wave absorbing pigments in the fish lens--I. Phylogenetic distribution and identity. AB - Fish lens transmission was found to vary depending on the type and concentration of short-wave absorbing compounds present within the lens. Pigments extracted from lenses of ten species were identified as mycosporine-like amino acids (mainly palythine, palythene and asterina-330, lambda maxs around 320-360 nm) which are also thought to be present in the majority of the 120 species examined here. A novel mycosporine-like pigment with lambda max 385 nm was isolated from the lens of the flying fish, Exocoetus obtusirostris, while lenses of several closely related tropical freshwater species were found to have high concentrations of the tryptophan catabolite 3-hydroxykynurenine (lambda max 370 nm). The type of lens pigment a species possesses and its concentration depends upon both the animal's phylogenetic group and its "optical niche". PMID- 8447102 TI - Spectral transmission and short-wave absorbing pigments in the fish lens--II. Effects of age. AB - Examination of the spectral transmission and pigments present in lenses of sixteen species of fish revealed that changes in lens pigment type and/or concentration often occur with age. Age-related changes in lens transmission for all species could be fitted to a common framework composed of three stages: an initial rapid accumulation of lens pigments producing a large increase in the wavelength of 50% transmission, followed by a reduction in the rate of pigment deposition which results in a levelling of the 50% transmission and a final stage after pigment accumulation ceases producing a drop in the wavelength of 50% transmission. PMID- 8447103 TI - Stereo and motion disparities interfere with positional averaging. AB - If required to judge the spatial separation between features that are sub-parts of larger objects, observers are biased in the direction of reporting the separation between the centroids of the objects. We predicted that this bias would be overcome by separating the target features from the larger objects, either by stereoscopic disparity or by relative motion. We measured the observer's perceptual biases for the "cluster illusion" with the target dots specified by: (1) contrast alone, (2) contrast and disparity, (3) disparity alone, (4) contrast and motion, and (5) motion alone. Disparity had the effect predicted, but the effects of motion were less clear. PMID- 8447104 TI - Surface segmentation mechanisms and motion perception. AB - Two studies are presented which explore how depth information is determined from conditions of transparency and whether this information combines with other depth information to determine the segmenting of motion information on the basis of likely surface boundaries. The first study explored how binocular disparity combines with monocular depth cues associated with transparency to determine whether subjects see one or multiple surfaces in depth in static displays. When transparency provided a depth cue that was consistent with binocular disparity, depth discrimination thresholds were at normal levels. However, if transparency was inconsistent with the binocular disparity, depth discrimination thresholds were elevated, indicating that subjects had difficulty seeing distinct surfaces lying in separate depth planes. Moreover, threshold elevations were found to correspond to the reductions in contrast between the intersecting contours of the stimulus, suggesting that the strength of perceived depth from transparency is the result of attenuated responses from competing contrast sensitive T-junction mechanisms responsible for the detection of opaque occlusion. A second experiment explored whether the grouping of local motion signals relied on surface interpretations that result from the interaction of transparency and disparity. Surface interpretations were manipulated in moving plaids by combining transparent layering and binocular disparity to show that the motion arising from contours is grouped together (pattern motion) when these cues support the existence of a single surface, and is segregated (component motion) when they support separate surfaces. When these cues were consistent, only small disparity differences were required for the gratings to appear as separately moving surfaces. However, when they were inconsistent, greater disparities were required (about a factor of 2 greater). Taken together, these studies demonstrate that the grouping of local motion information is not resolved within the motion system alone. Information seemingly unrelated to motion processing, namely surface segmentation cues, is used to determine whether or not motion information arising from various contours is pooled together to determine a single motion. PMID- 8447105 TI - The cue for contour-curvature discrimination. AB - Seven potential geometric cues for contour-curvature discrimination were tested: curvature, turning-angle, arc-length, arc-length-divided-by-chord-length, maximum deviation (sag), mean-deviation and area. Three experiments were performed, each requiring the discrimination of two simultaneously presented, 1-sec-duration, curved-line stimuli, whose chord-lengths ranged from 12 to 48 arcmin visual angle and whose curvatures ranged from 0 to 0.13 arcmin-1. Experiments 1 and 2 determined for each cue the smallest detectable increment (the increment threshold) as a function of cue value, for a set of spatial transformations of the stimulus (one- and two-dimensional scalings) equivalent to changes in viewing distance and direction. In accordance with statistical estimation theory, the "best" cue was defined as the most efficient one, that is, the one which best accounted for the variance in the data. As a control, Expt 3 compared increment threshold functions for circular and elliptical arcs of constant chord-length and circular arcs of constant arc-length. Over all three experiments, only sag and its linear approximation, mean-deviation, accounted well for the variance in the data; sag provided the best predictor, and its increment-threshold function satisfied Weber's law over almost all of the stimulus range. Additionally, sag has a special theoretical property (shared only with mean-deviation and area): the relationship it defines (in proportional terms) between curved contours in an image of an object or a scene is constant and independent of viewing distance and direction. PMID- 8447106 TI - The effect of interactions between one-dimensional component gratings on two dimensional motion perception. AB - Ferrera and Wilson [(1990) Vision Research, 30, 273-287] reported veridical perception of the direction of motion of Type I plaids, whose component gratings span the resultant direction, but marked misperception of the direction of motion of Type II plaids, whose component gratings both lie on one side of the resultant direction. Because they failed to find any effect of component direction (angular) separation on this misperception, Ferrera and Wilson concluded that the misperception was not due to perceptual repulsion of component directions. We report that component direction repulsion does occur, that plaid direction misperception is tuned to component separation, with larger repulsions for smaller angles. It is concluded that there is no fundamental difference in direction coding for Type I and Type II plaids, and that Ferrera and Wilson failed to find a direction separation effect because the range of separations they used was insufficiently broad to detect the slope of the angular function. PMID- 8447107 TI - Determinants of two-dimensional motion aftereffects induced by simultaneously- and alternately-presented plaid components. AB - Wenderoth, Bray and Johnstone [(1988) Perception, 17, 81-91] measured motion aftereffects induced on stationary vertical sine-wave gratings by horizontally drifting two-dimensional patterns (plaids). The adapting plaid component gratings were simultaneously or alternately presented and were oriented left and right of vertical by 15, 45 or 75 degrees. It was found that aftereffects decreased linearly in the alternating conditions as the plaid component orientations changed but this was not the case in the simultaneous adaptation conditions, a finding taken to be consistent with the hypothesis that one-dimensional aftereffects have a low level site (possibly V1) whereas two-dimensional effects have a higher level site (possibly MT). In three experiments, we have examined in more detail the determinants of aftereffects induced by simultaneous and alternating plaid components. The data suggest that the mechanisms involved are more complex than those put forward by Wenderoth et al. and that plaid perception utilizes both higher and lower level processes which can be referred to, respectively, as an intersection of constraints algorithm and a moving "blob" detector. PMID- 8447108 TI - Slow control with eccentric targets: evidence against a position-corrective model. AB - Does slow control work by keeping the image at a particular retinal location (position-correction), or by keeping the image relatively stable on whatever position it occupies on the retina (velocity-correction)? The best prior evidence that slow control is not position-corrective was that a stable line of sight can be maintained anywhere on or within a small figure. This result, however, does not preclude position-correction with respect to an imagined reference position selected relative to the figure's contour. To test the importance of an imagined reference position, we compared slow control with targets for which selection of a stable reference position is easy (two points arranged symmetrically about the line of sight) and difficult (one or two points located on one side of the line of sight). We found that the stability, velocity and direction of slow control were the same with both kinds of targets. Slow drifts were in idiosyncratic directions, and not toward the eccentric target. Drift speed increased with eccentricity, but drifts did not exceed 10'/sec even at the largest eccentricity tested (4.1 degrees). The independence of slow control from the spatial configuration of the target shows that slow control does not work by bringing either a visible or an imagined reference position to the optimal fixation locus on the retina. The gradual loss of stability with increasing eccentricity is consistent with prior reports of a reduction in the number of motion detectors tuned to low velocities as eccentricity increases. We conclude that motion signals, not position signals, provide the sole sensory input to slow control. PMID- 8447109 TI - Individual differences in contrast sensitivity functions: the first four months of life in humans. AB - Contrast sensitivity functions of forty 4-month-old human infants were measured using a preferential-looking method and the method of constant stimuli. Circular sinewave gratings varied from 0.27 to 1.08 c/deg, contained eight unattenuated cycles (with edges tapered to uniform gray), and rose to the desired contrast in 2 sec. Log contrast sensitivities for variables close in spatial frequency correlated more highly than those that were farther apart in these data, and in data of 1-, 2-, and 3-month-olds from Banks and Salapatek [(1981) Journal of Experimental Child Psychology, 31, 1-45]. Factor analyses yielded at least two frequency-tuned factors per age group. Monte Carlo simulations of a quantitative model that shifts spatial mechanisms to higher frequencies with age reproduced the results for 4-month-olds, but simulations of adultlike, unshifting mechanisms did not. The data are consistent with the following conclusions: (a) individual differences in the sensitivity of spatial mechanisms may explain some individual differences in CSFs; (b) factor analysis may help to estimate mechanism tuning; and (c) spatial mechanisms may shift to higher frequencies during development. PMID- 8447110 TI - Long-term learning in vernier acuity: effects of stimulus orientation, range and of feedback. AB - In hyperacuity, as in many other tasks, performance improves with practice. To better understand the underlying mechanisms, we measured thresholds of 41 inexperienced observers for the discrimination of vernier displacements. In spite of considerable inter-individual differences, mean thresholds decreased monotonically over the 10,000 stimuli presented to each observer, if stimulus orientation was constant. Generalization of learning seemed to be possible across offset-ranges, but not across orientations. Learning was slightly faster with error feedback than without it in one experiment. These results effectively constrain the range of conceivable models for learning of hyperacuity. PMID- 8447111 TI - Serial spatial filters in vision. AB - Observers viewing two superimposed laser interference fringes of nearly equal spatial frequency see an illusory grating of low spatial frequency, even when the spatial frequency of the fringes exceeds the resolution limit. This grating is a product of nonlinear distortion within the visual system [MacLeod, Williams and Makous (1992) Vision Research, 32, 347-363]. By separately manipulating the spatial frequencies of the interference fringes and the distortion gratings, we decomposed the contrast sensitivity function into two serial components separated by the nonlinear process. Losses in the optics of the eye were avoided by use of laser interferometry. Spatial summation preceding the nonlinear stage was restricted to the light-collecting area of individual cones and was directly proportional to the diameters of cone inner segments at three retinal eccentricities; this suggests that light is trapped within cones at the level of their inner segments. Even 30 degrees from the fovea, the nonlinear stage precedes the site where separate signals from individual cones are no longer maintained; this leads us to suggest that the nonlinear process lies within the retina. In addition, spatial antagonism precedes the nonlinear stage; this places the nonlinear process at a site following the outer segments of the cones. Dichoptic presentation of the interference fringes failed to produce illusory gratings; that is, the nonlinearities within the binocular pathway do not produce distortions like those produced by the monocular nonlinearity. PMID- 8447112 TI - Oocyte development: molecular biology of the zona pellucida. PMID- 8447113 TI - The laminins: a family of basement membrane glycoproteins important in cell differentiation and tumor metastases. AB - Laminins are a family of basement membrane-derived glycoproteins that are very biologically active with a number of diverse cell types. The response of the cells is dependent on the cell type and various cell-specific intracellular events are activated. Multiple active sites on laminin and cellular receptors have been described. Both laminin and the synthetic peptides that define the active sites may have important clinical uses. For example, the neurite-promoting peptides may be useful in vivo in regeneration studies because of their potent activity with neural cells and their lack of antigenicity. Also, peptides, such as YIGSR, that inhibit angiogenesis are potentially useful for treating the vascularization of the eye that occurs in conditions such as diabetes mellitus. Likewise, the angiogenic peptide SIKVAV, because of its role in endothelial cell block vessel formation, may be useful for treating ischemia. The recent progress that has been made in characterizing basic mechanisms of action of laminin has laid the groundwork for more direct studies of its clinical relevance. PMID- 8447114 TI - 11 beta-hydroxysteroid dehydrogenase. PMID- 8447115 TI - Chagas' disease and blood transfusion: a New World problem? AB - American trypanosomiasis (Chagas' disease) can be transmitted by blood transfusion. For almost 40 years, this transmission has been limited to Latin America, but recently, three cases have been reported in the USA and Canada. With increasing emigration to North America and Europe, Chagas' disease may be introduced to the Northern hemisphere by transfusion of blood from carriers. This review will focus on the discovery, biology and antigenic profile of Trypanosoma cruzi (the aetiological agent of Chagas' disease), including the invertebrate vectors, animal reservoirs and transmission to humans, with special reference to blood transfusion. Finally, diagnostic tests and prophylactic measures for the prevention of Chagas' disease will be discussed. PMID- 8447116 TI - Factor VIII:c concentrate virus inactivated: progress in purification by using classic chromatographic methods. AB - This study was carried out with the aim of developing a production process for the manufacture of a highly purified factor VIII concentrate which is virus inactivated by pasteurization in liquid phase. Beside standard plasma protein separation techniques, the procedure uses a chromatographic step on anion exchanger, whose selectivity is increased by using high, but not destabilizing salt concentrations. The final product before stabilization has a specific activity higher than 300 IU/mg of protein, namely the highest specific activity reported for human factor VIII concentrates purified without the use of immunoadsorbents. PMID- 8447117 TI - Plasma-depleted platelet concentrates prepared with a new washing solution. AB - In certain clinical situations, complete removal of the plasma proteins from the platelet concentrates (PCs) is necessary by washing prior to transfusion. A simple electrolyte solution with a pH of 6.5 was developed for washing PCs. The platelet-rich plasma collected with acid-citrate-dextrose solution by apheresis in a 0.6-liter polyolefin bag was centrifuged. After removal of the supernatant plasma from pelleted platelet buttons, 200 ml of a washing solution consisting of 90 mM NaCl, 5 mM KCl, 3 mM MgCl2, 17 mM NaH2PO4, 8 mM Na2HPO4, 23 mM Na acetate, 17 mM Na3 citrate, 23.5 mM glucose, 2 mM adenine, 0.1% dextran, and 28.8 mM maltose (pH 6.5) was added to the pelleted platelet button. Steam sterilization of the solution was carried out under nitrogen to avoid caramelization of glucose. After resuspension of the pelleted platelet button with a washing solution and a second centrifugation, Seto additive solution (Seto sol, pH 7.4) was introduced into the bag to resuspend the platelet buttons for storage for 3 days at 22 degrees C. All of these procedures were completed within 3 h using a sterile docking device. In washed PCs, 99.1% of the plasma was removed and platelet recovery was 96%. The washed PCs were compared for 3 days with plasma poor PCs consisting of 11% plasma and 89% Seto solution. There were no significant differences in percent hypotonic shock response, aggregation, energy metabolism, and morphology of platelets between the two groups during 3 days, except for significant swelling of 3-day-old platelets in washed PCs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447118 TI - The donation cycle: a framework for the measurement and analysis of blood donor return behaviour. AB - The donation cycle represents a new framework for the measurement of blood donor return behaviour. Because it is based on the interval between successive donation attempts, it is more efficient than previously reported methods and the resulting data can be analysed using the statistical techniques for interval data. To illustrate the merits of this quantitative approach to the study of blood donor behaviour, the donation cycle framework is used to analyse the interval between the first and second donation attempts in a random sample (n = 5,183) of type 0, whole blood donors from the Gulf Coast Regional Blood Center. Simple statistical tools such as the log-rank test are employed to describe and to evaluate relative differences in the return behaviour of Rh-negative and Rh-positive donors. The analysis indicates that Rh-negative donors are significantly (p < 0.001) more likely than Rh-positive donors to attempt to donate on a second occasion. Kaplan Meier estimates of the survival function of these first-time donors reveal marked elevations in the rate of return exactly 52 weeks after the initial donation. The donation cycle paradigm provides transfusion researchers with quantitative tools which are essential for designing statistically efficient, prospective intervention studies. By using the knowledge which such studies could provide, blood banks might be better able to manage donor return behaviour and thereby the safety of the blood supply. PMID- 8447119 TI - Orosomucoid system: 17 additional orosomucoid variants and proposal for a new nomenclature. AB - There are two forms of orosomucoid (ORM) in the sera of most individuals. They are encoded by two separate but closely linked loci, ORM1 and ORM2. A number of variants have been identified in various populations. Duplication and nonexpression are also observed in some populations. Thus, the ORM system is very complicated and its nomenclature is very confusing. In order to propose a new nomenclature, ORM variants detected by several laboratories have been compared and characterized by isoelectric focusing (IEF) followed by immunoprinting. A total of 57 different alleles including 17 new ones were identified. The 27 alleles were assigned to the ORM1 locus, and the others to the ORM2 locus. The designations ORM*F1, ORM1*F2, ORM1*S and ORM2*M were adopted for the four common alleles instead of ORM1*1, ORM1*3, ORM1*2 and ORM2*1 (ORM2*A), respectively. The variants were designated alpha numerically according to their relative mobilities after IEF in a pH gradient of 4.5-5.4 with Triton X-100 and glycerol. For the duplicated genes a prefix is added to a combined name of two alleles, e.g. ORM1*dB9S. Silent alleles were named ORM1*Q0 and ORM2*Q0 conventionally. In addition, the effects of diseases to ORM band patterns after IEF are also discussed. PMID- 8447120 TI - Erythrocyte exchange in cerebral malaria. PMID- 8447121 TI - HTLV-I/II infection is absent among risk groups from Mexico City. PMID- 8447122 TI - Significance of p24 on immunoblot with a negative anti-HIV ELISA result. PMID- 8447123 TI - Postoperative complication rate of thoracotomy in patients with normal and abnormal pulmonary function. AB - Recent advances in perioperative monitoring, anesthesia, and postoperative care have resulted in a more generous attitude towards performing thoracic surgery in patients with reduced pulmonary function. In our hospital 100 patients admitted for thoracotomy with or without pulmonary resection were classified on the basis of their pulmonary function: group I (n = 33) normal, group II (n = 40) moderate reduction, group III (n = 27) marked reduction. The mean and standard deviation in groups I, II, and III were: FEV 1 in % VC: 78 +/- 6, 72 +/- 7, and 58 +/- 10; RV in % TLC: 24 +/- 7, 35 +/- 8, and 43 +/- 9; Resistance, kPal/1/sec: 0.2 versus 0.3 versus 0.5. After surgery there were three postoperative deaths from cardiovascular complications without respiratory failure; all 3 patients were in group II and younger than 70 years. Only one patient (classified as group III and 59 years old) died from a respiratory complication (respiratory insufficiency) after a palliative operation on a large adenocarcinoma. Our data demonstrate that markedly reduced preoperative lung function is not necessarily associated with high risk in thoracic surgery--even in elderly persons--provided intensive pre- and postoperative care is guaranteed. PMID- 8447124 TI - [Surgical management of coronary heart disease and simultaneous carotid artery stenosis]. AB - Simultaneous carotid endarterectomy and open-heart procedures (bypass, aortic and mitral valve replacement, arterial myxoma) were performed on 89 patients. The indication for carotid endarterectomy were either preoperative neurological symptoms (n = 36) or radiologically verified, hamodynamically relevant stenosis of more than 50-60% (n = 53). The postoperative course was uneventful in 80 patients (90%). Neurological complications occurred in 5 patients; 4 had required surgery for pre-operative neurological symptomatology and 1 of these patients died from postoperative stroke. Cardiac complications occurred in 4 patients, one of whom died because of bypass thrombosis with subsequent myocardial infarction. Many authors have different opinions regarding indication, technical procedures and optimum time of operation. We consider the simultaneous operative procedure of carotid endarterectomy and open heart procedures justified in view of the neurological complication rate of approximately 5% in our group of patients. PMID- 8447125 TI - [Surgical treatment of Bland-White-Garland syndrome in infants and children: experiences with revascularization techniques]. AB - In comparison with the older technique of ligation of the anomalous coronary artery in Bland-White-Garland syndrome, the various methods of revascularisation have in common the concept of a two coronary artery system. Between 1980 and 1992, 10 children from 6 weeks to 11 years of age (mean 2 years) underwent revascularisation: direct reimplantation of the coronary ostium from the pulmonary artery to the aorta (n = 7), modified implantation with coronary artery elongation (n = 1), bypasses using subclavian artery (n = 1) or the mammary artery (n = 1). Postoperatively, 2 infants died, both following direct reimplantation, resulting in an overall mortality of 20%. There was no late death. All children but one are asymptomatic and do not require medication on follow up for between 3 months and 12 years (mean 5 years) after the procedure. Echocardiography, cardiac catheterisation, and scintigraphy show a significant improvement of left ventricular function and, as a direct consequence, a decrease in preexisting mitral insufficiency. Hence any surgical manipulation at the mitral valve should be avoided at the initial operation. As a principle, the revascularisation procedure should be performed at the earliest possible time to avoid further ischemic myocardial damage. On long-term follow-up, ventricular function and prognosis of the residual low-degree mitral insufficiency remain unclear and require regular control examinations. PMID- 8447126 TI - [Antibacterial chemotherapy of "septic kidney"]. AB - In the present retrospective study we report on antibacterial chemotherapy in patients suffering from a septic kidney. The results were documented in a course table, in which the septic parameters were divided into scores from 0 to 4 allowing to follow each patient's course with respect to the indicated scores. Two antibacterial substances were applied as short infusions with intervals of 4 6 hours between the administration of the different substances (Innsbruck scheme of chemotherapy). In all cases within 6 days from the onset of this therapy the septic parameters turned to normal values. None of the 24 patients suffering from a severe course of urosepsis, all treated at the University Hospital of Urology in Innsbruck between 1980 and 1990, died. PMID- 8447127 TI - [Tarsal tunnel syndrome after non-dislocated fracture of the outer ankle joint (case report with review of the literature)]. AB - The authors are going to report on the case of a 32-year-old female patient suffering from a non-dislocated external ankle fracture which was submitted to conservative treatment. This treatment was complicated by the occurrence of a tarsal tunnel syndrome which required surgical revision. The cause of this complication may be seen in the development of a minor local hematoma in the course of the tibial nerve as well as in a convolution of varicose veins located in the region of the internal ankle. By describing this case the authors wish to point out that development of a tarsal tunnel syndrome may not only be due to ankle fractures treated by osteosynthetic management (as described in relevant literature) but also to relatively uncomplicated and almost non-dislocated external ankle fractures receiving conservative management. PMID- 8447128 TI - [From anatomy to andrology: on the development of medical specialty nomenclature]. PMID- 8447129 TI - [New, in Austria registered specialty drugs. Normoxin (moxonidine)]. PMID- 8447130 TI - Cholecystectomy and drainage: ultrasonographic and radioisotopic evaluation. AB - Eighty patients undergoing cholecystectomy were either assigned deliberately (n = 30) or randomized (n = 50) to drainage (n = 38) or nondrainage (n = 42). Subhepatic collections were seen on ultrasonography (US) after 48 to 72 hours in 12 of 35 patients with drainage and 24 of 42 patients without drainage (p < 0.05). Only two patients with subhepatic collections were symptomatic, and none required treatment. Postoperative infective complications were seen in 13 of 38 patients with drainage and with a collection, and none of the 18 patients without drainage and without a collection had postoperative infective complications (p < 0.05). Cholecystectomy was then performed in 100 patients without using a drain. BULIDA radioisotope scans revealed a bile leak in only 4 of 34 patients studied. Subhepatic collections were seen on US after 48 to 72 hours in 42 patients. The collection resolved in 22 patients and was smaller in 6 on repeat US. None of the patients with collection was symptomatic, and none required treatment. Postoperative infective complications were seen in 7 of 42 patients with a collection and 5 of 58 patients without a collection (not significant). We conclude that (1) cholecystectomy with drainage is associated with more infective complications than when a drain is not used; (2) cholecystectomy without drainage is safe; and (3) asymptomatic nonbilious subhepatic collections are common after cholecystectomy without drainage but do not require treatment, resolving spontaneously. PMID- 8447131 TI - Abdominal wall retraction during laparoscopic cholecystectomy. AB - Laparoscopic cholecystectomy has represented a potentially more morbid procedure than open cholecystectomy. Some of this morbidity has been due to complications associated with pneumoperitoneum. We have developed a technique that employs abdominal wall retraction during laparoscopic cholecystectomy and allows access to the right upper part of the abdomen without maintenance of pneumoperitoneum. Among 151 patients who underwent laparoscopic cholecystectomy using abdominal wall retraction there were no recognized adverse effects. Abdominal wall retraction enables the surgeon to minimize the risk of serious complications associated with pneumoperitoneum during laparoscopic cholecystectomy. PMID- 8447132 TI - Optimization of isolated hyperthermic limb perfusion. PMID- 8447133 TI - Laparoscopic cholecystectomy: experience of a single surgeon. AB - Gallbladder removal using laparoscopic techniques has rapidly been adopted by surgeons around the world. Questions have been raised concerning laparoscopic cholecystectomy, including the safety of the operation, its implications for management of common bile duct stones, and the means by which surgeons should be trained. In the present series, 424 patients were referred to a single surgeon for cholecystectomy during a 22-month period. A traditional open cholecystectomy was performed in 9 patients (2.1%) because of presumed contraindications to laparoscopic cholecystectomy. Laparoscopic cholecystectomy was attempted in the remaining 415 patients (97.9%). On the basis of preoperative investigations, 19 patients (4.6%) underwent endoscopic retrograde cholangiopancreatography. Endoscopic sphincterotomy and stone extraction were performed in the 13 patients (3.1%) demonstrating choledocholithiasis. Laparoscopic cholecystectomy was converted to an open operation in 8 patients (1.9%) owing to dense adhesions, obscure anatomy, or cholangiographic abnormalities. Laparoscopic cholecystectomy was successfully performed in 407 patients (96%) in 95 +/- 2 minutes (mean +/- SEM). Surgical trainees were involved in all operations and performed 68% of the procedures under supervision. Cystic duct cholangiograms were obtained selectively in 129 patients (30.4%). Intraoperative complications occurred in 3 patients, including 1 patient with a minor injury to the common bile duct (0.2%). There was no perioperative mortality, and major complications occurred in 6 patients (1.4%). Minor complications were seen in 12 others (2.8%), and one patient required reoperation for a trocar injury to the jejunum. Prolonged follow up has revealed one case of asymptomatic retained common bile duct stones (0.2%). Laparoscopic cholecystectomy can therefore be performed in more than 95% of patients with no mortality and minimal morbidity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447134 TI - Summary of NIH Consensus development conference "gallstones and laparoscopic cholecystectomy". PMID- 8447135 TI - Laparoscopic choledochoscopy and extraction of common bile duct stones. AB - Various strategies have been proposed for the treatment of common bile duct stones encountered during laparoscopic cholecystectomy (LC). Eighty-three patients who had choledocholithiasis discovered during or just prior to LC are included in this study. These patients were treated by various modalities including preoperative, intraoperative, and postoperative endoscopic retrograde cholangiopancreatography and sphincterotomy, laparoscopic choledochotomy, transcystic duct-common bile duct (TCD-CBD) exploration, and conventional "open" common duct exploration. Sixty-six patients were successfully treated with TCD CBD exploration. They were discharged on average 2.6 days postoperatively and were able to return to normal physical activities within 7 days of discharge. There was minimal morbidity and no mortality. The technique of TCD-CBD exploration is described in detail. The role of laparoscopic choledochotomy and endoscopic sphincterotomy for management of common duct stones in patients undergoing laparoscopic cholecystectomy appears limited. PMID- 8447136 TI - Laparoscopic appendectomy. AB - Appendectomy was performed using a laparoscopic approach in 915 patients. The collected data show that the technique is as feasible, rapid, and safe as open surgery. Few wound infections, minimal pain, and rapid postoperative mobilization are the main arguments in favor of laparoscopic appendectomy. The most important potential benefit, a lower incidence of long-term complications such as adhesive intestinal obstruction, remains to be confirmed by prolonged follow-up of our patients. PMID- 8447137 TI - Training for laparoscopic surgery. AB - Laparoscopic cholecystectomy has rapidly become the procedure of choice for most patients with symptomatic gallbladder disease. Laparoscopic surgery, however, has not been a required component of most general surgery training programs. The demonstrated efficacy of laparoscopic surgery dictates that this discipline be rapidly incorporated into residency programs. Laparoscopic cholecystectomy and other surgical endoscopic procedures have been an integral part of the training program at the University of Maryland since 1989. Currently, residents who are completing their training have performed on average 50 to 75 laparoscopic procedures as the primary surgeon and 25 to 30 as the first assistant. In addition to training future community and academic physicians, those surgeons currently in practice must receive appropriate instruction in laparoscopic surgery. Most practicing surgeons attend a 2- to 3-day intensive course offering both didactic and hands-on experience. Additional exposure to clinical cases is achieved by working with other surgeons with laparoscopic expertise. Full credentialing in laparoscopic cholecystectomy generally requires proctoring by a surgeon from the local community. Since 1990 faculty from the University of Maryland have been active in the local community serving as proctors to surgeons in 14 hospitals. PMID- 8447138 TI - Laparoscopic vagotomy for chronic duodenal ulcer disease. AB - Two laparoscopic procedures for treatment of chronic duodenal ulcer are described: bilateral truncal vagotomy with balloon pyloric dilatation and posterior truncal vagotomy with anterior lesser curve seromyotomy. The first procedure is simple to perform and easily reproducible, but the latter is preferred because it respects the physiology of the stomach. Thirty-six patients were operated on over a period of 18 months with good results comparable to those with open surgery. The indications for surgery were intractable chronic duodenal ulcers resistant to optimal medical therapy. There was no perioperative morbidity or mortality, and recurrent ulcers have not been demonstrated during early postoperative follow-up. The proper role of laparoscopic surgery in the arsenal of treatment of duodenal ulcers is unclear. The method of laparoscopic vagotomy requires rigorous experimental evaluation in specialized centers before widespread clinical application. Future multicentric prospective studies with long-term follow-up are necessary to assess the results of this innovative therapy of acid-peptic disease. PMID- 8447139 TI - Laparoscopic antireflux surgery and repair of hiatal hernia. AB - Laparoscopic mobilization of the esophagus and esophagogastric (O-G) junction enables the safe and effective performance of endoscopic antireflux surgery for intractable reflux esophagitis. The two antireflux procedures that we have evaluated in clinical practice at this institution are the ligamentum teres cardiopexy (n = 9) and partial posterior fundoplication (n = 5). More recently, laparoscopic repair of large symptomatic hiatal hernia (sliding, paraesophageal, and mixed) has also been introduced (n = 4). The procedure entails reduction of the hernia, mobilization of the O-G junction with crural repair by a continuous suture technique employing a special preformed jamming loop knot, followed by total fundoplication, which is fixed proximal to the anterior margin of the diaphragmatic hiatus and distal to the O-G junction. The early results (maximum follow-up 18 months) of this experience have been favorable, with minimal morbidity, early hospital discharge, and effective control of reflux symptoms without adverse sequelae. Laparoscopic antireflux surgery is an alternative to long-term medication in patients with intractable esophagitis, and laparoscopic repair of large hiatal hernias offers significant advantage over the conventional open surgical approach in terms of rapid convalescence. PMID- 8447140 TI - Management of groin hernias by laparoscopy. AB - The surgical treatment of groin hernias continues to undergo technical modifications. The introduction of minimally invasive surgery had added a possible new dimension, replacing an inguinal approach by laparoscopy. Conceived some 15 years ago, the thesis was subjected to a clinical trial where coincidental abdominal hernial openings were closed at laparotomy. This study was followed by an experimental study at which time the openings were closed laparoscopically. The satisfactory results led to the development of a stapling instrument that could be passed through a cannula at laparoscopy and used to close the abdominal hernial opening. The clinical trial of treating hernias by laparoscopy was originally directed to the management of indirect inguinal hernias, but its use has since been expanded to include treatment of direct, femoral, obturator, incarcerated, recurrent, and bilateral hernias. The laparoscopic anatomy of the inguinal hernia, different from that seen by an inguinal approach, is briefly reviewed. The details of the operative technique are presented, as are the bases of other laparoscopic techniques that have evolved. Thirty-one hernial orifices have been closed and followed over 18 months. The results appear to be satisfactory in 27 instances. There were early technical failures in 2: One patient developed a recurrence after 5 months, later shown to be due to a sliding hernia; and symptoms of meralgia paresthetica of indeterminate origin appeared in one case. The advantages over the traditional approach are described; the disadvantages of the laparoscopic approach are those of laparoscopy itself and the absence of a long-term follow-up. PMID- 8447141 TI - Laparoscopic colonic procedures. AB - With the advent and general acceptance of laparoscopy as a means of surgically treating intraabdominal disease processes, procedures on organs other than the gallbladder and female genital tract have slowly evolved. After developing basic techniques in an animal model, a clinical series (n = 19) of laparoscopic procedures for a variety of colonic lesions was undertaken and is herein presented. It included both malignant and nonmalignant disease processes and has carried an acceptable complication rate and survival. The average age of our patients was 68, and except for two extended postoperative hospitalizations and one death for non-procedure-related complications, the patients were generally ready for discharge in less than 96 hours. Our current techniques and indications for laparoscopic colonic surgery are detailed. PMID- 8447142 TI - Advances in gynecologic laparoscopic procedures. AB - Most gynecologic procedures can be accomplished using laparoscopic surgical techniques. Gynecologic laparoscopic procedures are described that involve the reproductive system, lymph node sampling, bowel and urinary tract repair, and abscess therapy. Laparoscopic surgery enhances the outcome of most current gynecologic procedures. PMID- 8447143 TI - Aberrant left hepatic artery arising from the left gastric artery and liver function after radical gastrectomy for gastric cancer. AB - An aberrant left hepatic artery, arising from the left gastric artery (LHLG), either as an accessory or replacing the left hepatic artery, is occasionally seen in patients with gastric cancer. Resection of LHLG, as part of the gastrectomy procedure, may cause liver dysfunction. The surgical records of a group of 141 patients who had undergone gastrectomy for gastric cancer following preoperative angiography were reviewed. Twenty-eight of the patients had an LHLG preoperatively; in 15 the artery was severed during surgery and in the remainder it was preserved. Postoperative liver function was assessed by measuring changes in lactate dehydrogenase, glutamic oxaloacetic transaminase, and glutamic pyruvic transaminase activities. The greatest changes in liver function were observed in patients in whom the LHLG has been severed; the changes in liver function among patients whose LHLGs were preserved were similar to those in patients who had no LHLG. Notably, the wider the area fed by the LHLG, the greater was the change in liver function. The observed liver dysfunctions were transient, however, and normal function resumed within 7 days after operation. PMID- 8447144 TI - Gastroplasty for obesity: long-term weight loss improved by vagotomy. AB - Sixty-nine (13M, 56F), severely obese patients (body mass index 47 kg/m2) have had vertical banded gastroplasty (GP) with 5-cm polypropylene mesh (n = 39) or fascia (n = 30) bands since 1981. Of these 69 patients, 30 also had truncal vagotomy (TVG) without drainage. Total office follow-up rate is 94%. During follow-up of 1 year or more (mean 60 months), 25 patients with vagotomy plus gastroplasty lost 33 +/- 3 kg, corresponding to 51% of excess weight, compared to 21 +/- 3 kg (34% excess weight) in the 34 patients having gastroplasty alone (p < 0.01). In patients followed > or = 5 years (mean 83 months) 10 patients with TVG lost 40 +/- 5 kg (61% of excess) compared to 17 +/- 4 kg (28% of excess) in 22 patients with GP alone (p < 0.001). Frequency and severity of complications were similar in both groups, but there were seven reoperations after GP and three after TVG (p < 0.05). Studies of gastric emptying of a solid meal in 14 of the patients with GP and 14 with TVG demonstrated greater weight loss in those with prolonged emptying and gastroesophageal pooling, though the emptying rates of patients with GP and those with TVG showed no statistically significant difference. Our earlier studies, which showed reduced liquid consumption after vagotomy, imply that this mechanism (rather than delayed emptying) explains why vagotomy potentiates weight loss after gastroplasty. PMID- 8447145 TI - Elective and emergent laparoscopy. AB - Although laparoscopy has been received enthusiastically by gastroenterologists, mainly in Europe, over the past four decades, its usefulness in surgery has been ill-defined or neglected. Gynecologists recognized the value and included laparoscopy as one of the most important diagnostic and therapeutic tools for pelvic pathology. After the introduction of laparoscopic cholecystectomy, several thousand surgeons were trained in laparoscopic techniques. Laparoscopy allows direct visualization of abdominal organs and the parietal peritoneum. It permits a safe target biopsy under precise visual control. The practical value of laparoscopy is the observation of lesions that would not be discovered by other investigations and the ability to assess the dissemination of malignant disease and its operability. Hence many unnecessary explorations are avoided. Diagnostic laparoscopy has a high overall diagnostic yield, has an excellent safety record in the hands of a well trained operator, and is cost-effective. Minilaparoscopy in the emergent (blunt abdominal) trauma case gives the surgeon a much larger latitude for decision making than does diagnostic peritoneal lavage. Emergency minilaparoscopy has been performed in 150 trauma patients and has accurately predicted the need for laparotomy in all but one patient (0.7%). No major complications have occurred as a result of minilaparoscopy in this setting. A large number of emergency laparotomies in the multiorgan-injured or high-risk case can be avoided. Minilaparoscopy may be useful also in the elderly patient with an equivocal abdominal examination but suspicion of visceral injury. PMID- 8447146 TI - Resting energy expenditure and nitrogen loss after surgery in chronically undernourished patients. AB - Chronically undernourished patients (n = 10) undergoing elective abdominal surgery were assessed with regard to their energy expenditure and urinary nitrogen loss. These measurements were made for 1 week after the surgery, and stress factors for each parameter were computed. The responses of the chronically undernourished patients were compared to those of relatively well nourished patients (n = 10) undergoing comparable surgeries. It was found that the postoperative resting energy expenditure (REE) of the chronically undernourished patients was not significantly elevated when compared to their preoperative values (mean +/- SEM): 1210.66 +/- 88.13, 1354.91 +/- 86.61, 1215.09 +/- 89.68, and 1188.23 +/- 86.61 kcal/day preoperatively and on postoperative days 1, 4, and 8, respectively. On the other hand, the postoperative REE of the controls was significantly elevated (p < 0.05) over their baseline values: 1357.18 +/- 70.81, 1574.66 +/- 100.35, 1502.89 +/- 109.44, and 1477.23 +/- 83.52; kcal/day, respectively, for the same days. The stress factors for the controls were higher than those for the undernourished (1.16 versus 1.12, 1.11 versus 1.00, and 1.09 versus 0.98 on postoperative days 1, 4, and 8, respectively). The urinary nitrogen excretion in both groups (for the 4 days) was not significantly elevated over baseline (6.23 +/- 0.87, 7.72 +/- 0.71, 8.36 +/- 0.87, and 8.04 +/- 1.56 grams/day in the undernourished; and 7.59 +/- 1.03, 9.57 +/- 1.33, 9.49 +/- 1.03, and 8.67 +/- 0.76 grams/day in the controls. The stress factors for nitrogen excretion were slightly higher in the undernourished group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447147 TI - Surgical treatment of carcinoma of the hepatic duct confluence: analysis of 55 resected carcinomas. AB - We treated 65 patients with carcinoma of the hepatic duct confluence between 1976 and 1991, 57 (87.7%) of whom were treated surgically; of the 57, 55(96.5%) underwent resection. Radical resection was performed at a rate of 50.9%. Procedures for these 55 patients included resection of the extrahepatic bile duct plus hepatectomy (n = 33; 60.0%), and resection of the duct without hepatectomy (n = 22; 40.0%). In addition, the caudate lobe was resected in 28 of these patients, and the portal vein, hepatic artery, or both were resected in 6. The overall operative morbidity was 21.8%; morbidity occurred in 33.3% of patients with hepatectomy, a significantly higher percent than the 4.5% rate in those without hepatectomy (p < 0.05). Operative death occurred in only 1.9%. As the depth of cancer invasion in the bile duct wall advanced, the incidence of tumor spread (e.g., lymphatic permeation, venous invasion, perineural invasion, lymph node metastasis) increased significantly. The prevalence of extramural tumor extensions in a transverse direction was higher than that in the longitudinal direction along the bile duct wall; and the distance from the margin of the primary tumor to the site of tumor extensions along the bile duct wall was much longer on the hepatic side than on the duodenal side. Cancer invasion of the caudate lobe was observed in 36.4%, and invasion at the surgical margins was found more frequently in those without hepatectomy than those with hepatectomy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447149 TI - Esaprazole effect on acid, peptic and alkaline secretion in duodenal ulcer patients. AB - To study the effect of Esaprazole, a new antiulcer drug, on acid, peptic and alkaline secretion a modified gastric acid test was performed in 18 duodenal ulcer patients. Pentagastrin was administered as bolus 30' and 75' after the beginning of the test, followed by Esaprazole 300 mg i.v. at 90'. Gastric juice was collected every 15' for determination of: total volume, volume of non parietal secretion, acid, bicarbonate and pepsin output. Serum pepsinogen group I was determined by radioimmunoassay. Esaprazole had a significant inhibitory effect on the total volume of gastric secretion and on volume of non parietal secretion. Pepsin output and serum pepsinogen group I were not affected by Esaprazole, while bicarbonate secretion was reduced. Antiulcer activity of Esaprazole seems to be due to the reduction of total volume of gastric secretion. PMID- 8447150 TI - Antipyrine elimination in patients with alcoholic and non-alcoholic cirrhosis. AB - The metabolism of antipyrine to each of its three major metabolites 4-hydroxy-, 3 methylhydroxy- and norantipyrine has previously been demonstrated to be differentially affected in alcoholic cirrhosis. This study compared the metabolism of antipyrine to its metabolites in 30 patients with alcoholic cirrhosis to 15 patients with non-alcoholic cirrhosis and 20 healthy controls. Both groups of cirrhotic patients were comparable with respect to their disease stage, as assessed by the Child-Pugh classification. Compared to controls, patients with alcoholic and non-alcoholic cirrhosis showed a comparable significant reduction in antipyrine clearance and increase in antipyrine half life. The reduction in antipyrine clearance was due to a reduction in the formation rate of all three antipyrine metabolites in both alcoholic and non alcoholic cirrhotics. In both groups, the formation rate of norantipyrine was reduced to a greater extent than of 3-methylhydroxy- and 4-hydroxyantipyrine. No significant differences in the parameters of antipyrine elimination, however, were observed between patients with alcoholic and non-alcoholic cirrhosis. Parameters of antipyrine elimination correlated significantly to the Child-Pugh score and single laboratory parameters, however, the correlation coefficients were generally low (< 0.56). The present results suggest that the P450 enzymes involved in antipyrine metabolism are differentially affected in cirrhosis, but there appear to be no differences in the activity of the enzymes between alcoholic and non-alcoholic cirrhosis. Antipyrine metabolism, therefore, depends on the severity rather than the etiology of liver disease and may serve as a measure of hepatic function irrespective of the cause of liver disease. PMID- 8447148 TI - Preventive effect of nicardipine on hyperplastic changes in venous bypass grafts. AB - Nicardipine is a relatively new calcium channel blocker with important properties that could result in attenuation of the adverse proliferative changes in autogenous vein bypass grafts. In this experimental, randomized, controlled study, the effect of nicardipine on the pathologic findings in aortoaortic bypass graft was assessed. Forty-two male rabbits (Orycytolagus cuniculus) were randomized to three groups: group 1 received nicardipine and groups 2 and 3 placebo for 4 weeks, after which an aortaortic bypass was realized with an autogenous inferior vena cava segment. During the following 4 weeks, groups 1 and 2 received nicardipine, and placebo was continued in group 3. The animals were sacrificed at the end of the study to permit removal and evaluation of the bypass grafts. The mean intimal and medial thickness values for groups 1 and 2 were lower than those for group 3, indicating that nicardipine has a significant preventive effect on the hyperplastic changes in venous bypass grafts compared to placebo. The mean intimal and medial thickness values of group 1 were also lower than those of group 2, and the differences carried statistical relevance, suggesting that the use of nicardipine before grafting could potentiate its protective effect. To provide stimulus for further research, an attempt is made to relate the hyperplasia-preventing effect of nicardipine to possible mechanisms. PMID- 8447151 TI - [Endogenous and exogenous factors in tumor development and cell differentiation in gastrointestinal tumors]. AB - In recent years, epidemiological and molecular studies revealed very important new insights into the development of tumors in the gastrointestinal tract. Above all, certain forms of nutrition and molecular genetic features and events are responsible for tumor occurrence. This article tries to give a short review of the most important recent findings in this field of research. PMID- 8447152 TI - [Cloning the gastrin receptor of the parietal cell--resolving an old controversy]. PMID- 8447153 TI - Breath hydrogen excretion in patients with alcoholic liver disease--evidence of small intestinal bacterial overgrowth. AB - The hydrogen breath test has been used to investigate the incidence of small bowel bacterial overgrowth in 45 chronic alcoholics and in 60 controls with no history of alcohol abuse. In the group of patients with alcoholic liver disease, the percentage of cases with bacterial overgrowth was almost three times (37.8%) that of controls not abusing alcohol (13.3%; p < 0.001). A separate evaluation of alcoholics with cirrhosis in comparison with those without cirrhosis, revealed no significant difference in the incidence of bacterial overgrowth (42.9% and 33.3%; p > 0.05). Some 16.7% of the controls and 8.9% of the patients with alcoholic liver disease were classified as "non-excreters". Among patients with alcoholic liver disease, the mouth-to-caecum transit time was prolonged by 21.5% in comparison with the controls not abusing alcohol (p < 0.025). The results suggest that bacterial overgrowth might contribute to the functional and/or morphological abnormalities of the small intestine commonly found in patients with chronic alcohol abuse. PMID- 8447154 TI - [Cloning the CCK receptor]. PMID- 8447155 TI - [German Association for the Study of the Liver (GASL), 9th meeting. Berlin, January 29-30, 1993. Abstracts]. PMID- 8447156 TI - Potentially negative effects of AIDS vaccines based on recombinant viruses carrying HIV-1 derived envelope gene. A warning on AIDS vaccine development. AB - Various candidate AIDS vaccines based on HIV-1 envelope glycoprotein (gp120/160) are currently under clinical trials (phase 1 and 2) in healthy, HIV-negative volunteers, as well as in HIV-infected persons. Most of these vaccines use recombinant viral vectors carrying the HIV-derived gp120/160 gene. Possible negative effects of recently reported sequence and gene similarities between HIV 1 gp120 and the variable region of human immunoglobulins on further development and current application of such AIDS vaccines are discussed. PMID- 8447157 TI - Adjuvants--a balance between toxicity and adjuvanticity. AB - Adjuvants have been used to augment the immune response in experimental immunology as well as in practical vaccination for more than 60 years. The chemical nature of adjuvants, their mode of action and the profile of their side effects are highly variable. Some of the side effects can be ascribed to an unintentional stimulation of different mechanisms of the immune system whereas others may reflect general adverse pharmacological reactions. The most common adjuvants for human use today are still aluminium hydroxide, aluminium phosphate and calcium phosphate although oil emulsions, products from bacteria and their synthetic derivatives as well as liposomes have also been tested or used in humans. In recent years monophosphoryl lipid A, ISCOMs with Quil-A and Syntex adjuvant formulation (SAF) containing the threonyl derivative of muramyl dipeptide have been under consideration for use as adjuvants in humans. At present the choice of adjuvants for human vaccination reflects a compromise between a requirement for adjuvanticity and an acceptable low level of side effects. PMID- 8447158 TI - Experimental immunity against trypanosomiasis in rabbits. AB - Rabbits were immunized with specially prepared subcellular fractions of a cloned Trypanosoma brucei brucei stock 427. One fraction was found to be highly immunoprophylactic in rabbits exposed to the vector fly genus Glossina m. morsitans (tsetse flies) infected with EATRO Trypanosoma brucei brucei 1969. The most immunoprotective fraction IPFA from T. b. brucei 427 gave 75% protection to animals challenged by EATRO T. b. brucei 1969. IPFA also showed the highest IgG antibody titre against the heterologous and homologous strains. In in vitro studies, the sera from these immunized rabbits killed different strains of parasites, T.b. brucei strains 1969 and 999 which were grown in continuous culture of salivary gland cells from G.m. morsitans. PMID- 8447159 TI - Protection against airsacculitis with sequential systemic and local immunization of chickens using killed Mycoplasma gallisepticum bacterin with iota carrageenan adjuvant. AB - The induction of protective immunity to Mycoplasma gallisepticum (MG) by bacterins containing 0.2% iota carrageenan (iCGN) as an adjuvant has been studied. Various combinations of intracoelomic (i.c.), intratracheal (i.t.), intranasal (i.n.), intravenous (i.v.), subcutaneous (s.c.) and oral immunization routes were evaluated. Vaccinated and non-vaccinated groups were compared with a group vaccinated s.c. with a commercial bacterin. Primary i.c. immunization with the bacterin was as effective as commercial bacterin and was more effective when followed by i.n. or i.t. immunization. Oral immunization was ineffective, in contrast to observations reported with mice. The i.c./i.n. and i.c./i.t. combinations were the most effective, produced the highest levels of anti-MG IgG and IgA in serum and tracheobronchial washes, and sometimes provided 100% protection against air sac lesions. Chickens vaccinated by the i.c./i.n. or i.c./i.t. routes had the fewest virulent organisms in their respiratory tract secretions. These results demonstrated that i.c. immunization followed by local immunization with the bacterin is most efficacious in protecting chickens against airsacculitis. PMID- 8447160 TI - Quantification of pertussis toxin, filamentous haemagglutinin, 69 kDa outer membrane protein, agglutinogens 2 and 3 and lipopolysaccharide in the Danish whole-cell pertussis vaccine. AB - The amounts of pertussis toxin (PT), filamentous haemagglutinin (FHA), 69 kDa outer membrane protein (69 kDa OMP) and agglutinogens (AGG) 2 and 3 in extracts from the Danish whole-cell pertussis vaccine were studied in quantitative capture ELISA. With the exception of PT, the most effective extraction of these antigens was by heating the bacteria at 60 degrees C for 30 min in 2 M urea followed by sonication for 45 s. Extraction by 1 M sodium chloride prior to sonication resulted in higher levels of antigenic and biologically active PT. On average, a single human dose of pertussis vaccine (approximately 16 opacity units) was found to contain 5520 ng FHA, 63 ng PT, 1061 ng 69 kDa OMP, 397 ng AGG 2, 534 ng AGG 3 and 4840 ng lipopolysaccharide (LPS). The antigen content of one dose of the Danish pertussis vaccine appears to be low compared with the amounts found in the acellular vaccines currently in use. These findings may have important implications for the evaluation of the protective substances and the immunogenicity of whole-cell as opposed to acellular pertussis vaccines. PMID- 8447161 TI - Comparison of live attenuated and inactivated influenza vaccines in schoolchildren in Russia: I. Safety and efficacy in two Moscow schools, 1987/88. AB - The performance of two doses of cold-adapted live attenuated vaccine versus one dose of whole-virus inactivated vaccine was compared in 8-15-year-old schoolchildren in two schools in Moscow, Russia, during the winter of 1987/88. Both vaccines gave rise to low frequencies of associated febrile or systemic reactions, but the inactivated vaccine, delivered by jet injector, did cause small local reactions in about half of the children. Immunogenicity was higher for both vaccines in antibody-free children, and higher levels of serum antibody were detected following use of inactivated vaccine. During the winter, influenza A (H3N2) and influenza B viruses circulated in Moscow. A clear outbreak of (H3N2) virus occurred in both schools, and infections with type B virus also occurred in one school. The influenza A/Philippines/2/82 (H3N2) component of both vaccines exhibited protective efficacy of about 40% (p < 0.05) against serologically proven infection caused by the antigenically drifted A/Sichuan/2/87 (H3N2)-like epidemic viruses in one school. In another school where illnesses associated with antibody rise were documented, efficacy was seen for both vaccines in reduction of illnesses, and of illnesses with serological evidence of infection, but statistical significance was not achieved. PMID- 8447162 TI - Principles of selective inactivation of viral genome. VIII. The influence of beta propiolactone on immunogenic and protective activities of influenza virus. AB - The influence of beta-propiolactone action on the immunogenic and protective activity of the influenza virus A/WSN/33 (H1N1) has been studied. The production of antibodies against virion surface antigens in mice immunized intramuscularly by the modified virus was enhanced with the increase of inoculating dose from 6 x 10(7) to 1.5 x 10(8) viral particles per animal. The immunizing dose of 6 x 10(7) produced complete protection of immunized animals against a lethal challenge of A/WSN/33 virus. The inhibition of virus reproduction in animal lungs was increased with the increase of the virus immunizing dose up to 6 x 10(8). At a constant dose the inhibition of virus reproduction decreases with the increase of the virus modification extent. PMID- 8447163 TI - A self-associating hepatitis B surface antigen-derived peptide that is immunogenic in alum. AB - We previously described an oligomeric synthetic peptide derived from the hepatitis B surface antigen that displayed a limited tendency to form self associating macromolecular structures in solution. Here it is demonstrated that amino-terminal myristylation of this peptide results in near quantitative aggregation of the oligomeric peptide. The myristylated peptide is highly immunogenic when used in conjunction with alum as adjuvant in both the rabbit and rhesus monkey models. The antibody response generated by peptide also cross reacted with native antigen and was long-lasting. Collectively the results described in this and previous reports offer an attractive new approach for generating immunogenic peptide mimetics of conformational epitopes that may find application as vaccines. PMID- 8447164 TI - Identification of the flagellar antigens of Vibrio cholerae El Tor and their role in protection. AB - Antiserum to the surface antigens of the wild-type flagellate strain KB207 of Vibrio cholerae El Tor was absorbed with isogenic aflagellate mutant CD12. Antibodies remaining in the absorbed serum exhibited specificity to KB207 but not to CD12 and inhibited motility of KB207. Proteins from cell-free lysates of KB207 and CD12 were analysed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. CD12 differed from KB207 in the absence of two proteins of 40 and 38 kDa. These proteins were detected in KB207 when electrophoretically separated proteins were immunoblotted with unabsorbed and absorbed sera. These two proteins were isolated by immunoaffinity chromatography using purified antibodies from absorbed serum. Although antigenic, the 40 and 38 kDa proteins did not induce protection against cholera in the rabbit ileal loop model. PMID- 8447165 TI - Identification of a 33 kDa antigen associated with an adhesive and colonizing strain of Vibrio cholerae El Tor and its role in protection. AB - Proteins from the cell-free lysates of the wild-type strain KB207 of Vibrio cholerae El Tor and the isogenic non-adhesive mutant CD11 were analysed by native and denaturing polyacrylamide gel electrophoresis. A protein of 33 kDa present in KB207 was absent from CD11. Antiserum to the surface antigens of KB207 was absorbed with CD11. Antibodies remaining in the serum after absorption reacted to KB207 but not to CD11 as judged by slide agglutination, double gel diffusion and dot blot ELISA. Antibodies in the absorbed serum inhibited adherence of KB207 to rabbit intestinal mucosa and colonization in an infant mice model. The 33 kDa protein was isolated from KB207 by immunoaffinity chromatography. Antibodies present in the absorbed serum were used as ligand. The 33 kDa antigen was immunogenic and conferred protection in the rabbit ileal loop model. Combined administration of 33 kDa protein and B-subunit of cholera toxin offered full protection. PMID- 8447166 TI - Novel strategies for an effective measles vaccination programme under field conditions. PMID- 8447167 TI - Strategies for immunization against hepatitis B in western Europe. AB - In western Europe there has been a striking decline in the incidence of hepatitis B virus infection during the second half of the 1980s. Only a minor part of this decrease is the effect of vaccination, since rather limited vaccination programmes have been introduced in most west European countries. The policies for recommendation of hepatitis B vaccination have differed from north to south in Europe due to different risks of exposure to hepatitis B virus. In Scandinavia, vaccination has mainly been recommended for health-care workers with frequent blood contact, while in Germany and in France vaccination has been recommended for all health-care workers with patient contact. Further south, as in Italy, all health-care workers have been considered a risk group, and vaccination is recommended for all newly recruited workers and students. PMID- 8447168 TI - Control of hepatitis B through routine immunization of infants: the need for flexible schedules and new combination vaccine formulations. AB - Universal immunization of infants is essential to the control of hepatitis B in areas of high endemicity where infection commonly occurs in infants and children. It is also an attractive strategy for ultimately reducing hepatitis-B-associated acute and chronic liver disease in areas of lower endemicity where infections occur primarily in adolescents and adults. Integration of hepatitis B vaccine with other routine paediatric immunizations, using flexible scheduling, will enhance compliance while minimizing the need for additional resources. Clinical studies demonstrate that a very high proportion of healthy infants and adults develop a protective level of antibody when given hepatitis B vaccine using a wide range of schedules. Compliance with universal vaccination of infants against hepatitis B may be enhanced by the development of new combination vaccines (e.g. diphtheria-tetanus-pertussis-Haemophilus influenzae b-hepatitis B) that allow complete immunization against several antigens with a minimal number of injections. PMID- 8447169 TI - World-wide strategies for immunization against invasive Haemophilus influenzae type b disease. AB - Data available on the immunogenicity, safety and efficacy of Haemophilus influenzae type b (Hib) conjugate vaccines are encouraging and the prospects for controlling invasive Hib disease are good. The incidence of Hib meningitis in many industrialized countries increases sharply between 6 and 12 months of age and the first two doses of a Hib vaccine should ideally be given before that. In non-industrialized countries, the incidence peak is seen very early in life, which would require a very early start for Hib vaccination in such areas. PMID- 8447170 TI - New vaccines for humans. PMID- 8447171 TI - Epidemiology of invasive Haemophilus influenzae type b disease in Scandinavia. AB - In all Scandinavian countries, most invasive Haemophilus influenzae type b (Hib) infections occur before the age of 5 years. The age-specific incidence of Hib meningitis in this age group is 26-35/100,000 per year in Denmark, Norway, Finland and Sweden and about 43/100,000 per year in Iceland. Of the meningitis patients, approximately 60% are younger than 2 years but Hib meningitis also occurs in older children and adults. The case fatality rate is low (1-3%) in children but the rate of neurological sequelae is considerable. The incidence of acute epiglottitis, the other main manifestation of Hib disease, varies considerably. In Sweden, four studies have shown a very high incidence in the age group 0-4 years, 21-34 cases/100,000 population per year compared to only 5-17 in the other Nordic countries. Epiglottitis is more common than Hib meningitis in older children and adults. In Scandinavia the age-specific incidence of all invasive Hib infections could be estimated to be about 50-65/100,000 per year in the most susceptible age group and the risk of contracting invasive Hib disease before the age of 15 years would be about 1/200-300 children. PMID- 8447172 TI - Need for prevention of invasive Haemophilus influenzae type b infections in Geneva, Switzerland. AB - Based on a retrospective study of invasive Haemophilus influenzae type b (Hib) diseases in Geneva from 1976 to 1989, we analysed the need for prevention of invasive Hib infections by vaccination in Geneva, Switzerland. The overall incidence rate among children younger than 5 years of age was 60.2/100,000 population but it was 121.5/100,000 and 92.1/100,000 in 1988 and 1989 respectively, indicating a statistically significant increase of invasive Hib infections during the study period. Of patients, 41.5% had meningitis, 36.6% epiglottitis and 21.9% had other forms of Hib infections. The occurrence was 2.1% in children under 3 months of age and 92.3% in children younger than 5 years of age. From 1984, > 21% of all new isolates were beta-lactamase-producing Hib strains. From 1976 to 1989, two children (1.1%) died from epiglottitis and 12 children with meningitis (15.8%) developed serious neurological deficits. These data emphasize the need for prevention of invasive Hib infections by vaccination in all infants in Geneva. PMID- 8447173 TI - Epidemiology of Haemophilus influenzae type b disease in France. AB - Results are reported of an epidemiological study which spanned ten years and was carried out in two French departments. A total of 277 cases of Hib disease occurring in children < 5 years old are reported and, in this age group, the incidence is evaluated at 21/100,000. Meningitis accounted for 64% of infections and epiglottitis for 7%. While the overall mortality rate was 3.3%, death was secondary to meningitis in 7/8 cases. Sequelae, which were all related to meningitis, were major in 1.2% of cases, severe in 9% of cases, and involved some hearing loss in 3.3% of cases. The monitoring networks set up in the two departments were characterized by sensitivities of 87 and 94%, respectively. They should prove useful in assessing the impact of vaccination, when large-scale implementation of vaccination has spread to both departments. PMID- 8447174 TI - Vaccination strategies for the 1990s. Oslo, Norway, 10-11 September 1991. PMID- 8447175 TI - Epidemiology of invasive Haemophilus influenzae type b (Hib) disease in Israel. AB - The results are reported of a nationwide prospective epidemiological study in Israel whose purpose was to provide a background for decisions regarding the need for Hib conjugate vaccinations. During the two study years, 344 patients < 13 years of age with a positive blood or cerebrospinal fluid culture for Hib were seen in 25 medical centres in which paediatric patients were hospitalized. The overall incidence of Hib disease was 34 per 100,000 persons < 5 years old, an incidence in the range of those reported for western Europe. Similarly, the incidence of meningitis was 18/100,000. During the first year of life, the incidence of Hib was 117/100,000 and 93% of all cases were < or = 24 months old. The age distribution of our patients resembles that of immunologically compromised populations or of persons living in less industrialized areas, but the incidence of disease is similar to that found in western Europe. The data presented justify the widespread use of conjugate Hib vaccines in Israel. PMID- 8447176 TI - Effect of immunity to the carrier protein on antibody responses to Haemophilus influenzae type b conjugate vaccines. AB - The anticapsular antibody responses to some Haemophilus influenzae type b (Hib) conjugate vaccines may be enhanced by prior or simultaneous administration of the carrier protein used in the conjugate. Currently, there are two Hib conjugate vaccines licensed in the USA for use in infants beginning at 2 months of age: Hib polysaccharide coupled to an outer membrane protein complex of Neisseria meningitidis (PRP-OMPC), and Hib oligosaccharides conjugated to CRM197, a non toxic mutant diphtheria toxin (HbOC). The PRP-OMPC conjugate vaccine is immunogenic in infant monkeys and infant humans in the absence of carrier priming or additional carrier vaccination. The mechanism responsible for this immunogenicity is unknown but may relate to the adjuvanticity of the OMPC carrier. In contrast, data from infant rhesus monkeys and infant humans suggest that there may be a need for vaccination with diphtheria toxoid in order to maximize anti-PRP antibody responses to the HbOC conjugate. In addition, immunization with HbOC alone appears to be insufficient to elicit an antibody response to diphtheria toxoid. Thus, the need for additional vaccination with diphtheria toxoid in order to generate consistent anti-PRP antibody responses to HbOC may be a result of failure of the CRM197 protein carrier to elicit T-cell help. In infants in whom diphtheria-tetanus-pertussis (DTP) vaccination is deferred because of medical contraindications, vaccination with the PRP-OMPC conjugate would appear to be preferable to HbOC because of the ability of the former to elicit antibody responses in the absence of diphtheria toxoid vaccination. PMID- 8447177 TI - Prevention of Haemophilus influenzae type b disease. AB - Haemophilus influenzae type b (Hib) is the leading cause of meningitis in children < 5 years of age. The majority of cases of Hib occur in infants < 2 years of age. Until recently the only vaccine available against this disease contained the pure polysaccharide (PRP) of Hib (Hib-PRP vaccine). The Hib-PRP vaccine was demonstrated to be efficacious in infants > 18 months of age but not below that age. This product was licensed for routine use in the USA for children aged 24 months or more. Recently a hyperimmune globulin termed bacterial polysaccharide immune globulin (BPIg) was prepared by immunizing adult donors with Hib-PRP, meningococcal and pneumococcal vaccines. BPIg has been demonstrated to prevent Hib infections when it is administered to infants at 4-month intervals. However, BPIg has not been licensed for routine use in the USA. A number of new Hib conjugate vaccines have also been developed in the last few years by convalently linking the Hib-PRP to different carrier proteins. Four different Hib conjugate vaccines have undergone clinical trials in the USA. Two of these vaccines, HbOC (Hib capsular oligosaccharide linked to CRM197) and Hib OMPC (Hib capsular polysaccharide linked to Neisseria meningitidis outer membrane protein complex) have been demonstrated to protect infants aged 2 months or more from Hib disease. Both HbOC and Hib-OMPC are currently licensed for routine use in the USA. The widespread use of these vaccines should have a substantial impact in reducing morbidity and mortality from Hib disease. PMID- 8447178 TI - Anti-PRP antibody levels after a primary series of PRP-OMPC and persistence of antibody titres following primary and booster doses. AB - The Haemophilus influenzae capsular polysaccharide-outer membrane protein conjugate, PRP-OMPC (PedvaxHIB) elicits very good antibody responses in infants > or = 2 months of age after the first dose. Increasing age at time of first vaccination correlates with higher antibody responses. Anti-PRP responses are consistently high with the first injection among all population groups studied. Booster doses stimulate anamnestic antibody responses after one year of age. Among US children (excluding Navajo and Apache children) given a primary injection at 14-18 months of age, the geometric mean titre (GMT) after 2 to 3 years was > 1 micrograms/ml. US children (excluding Navajo and Apache children) given a primary series at 2 and 4 months of age and a booster at 18 months of age also had an anti-PRP GMT > 1 micrograms/ml 2.5 years later. Navajo and Apache children given a primary series at 2 and 4 months of age and a booster at 12-15 months had antibody levels of 1.50 micrograms/ml one year later. Antibody persistence data suggest there will be long-term protection against Haemophilus influenzae b disease following immunization with PRP-OMPC. PMID- 8447179 TI - A small open reading frame of the hepatitis delta virus antigenomic RNA encodes a protein that elicits antibodies in some infected patients. AB - A small open reading frame (ORF) was found in the hepatitis delta virus (HDV) antigenomic RNA encoding a short peptide that shares structural similarity with a region of the hepatitis B virus terminal protein. Analysis of all published HDV genome sequences indicates a high degree of conservation for the small ORF. This ORF is located at the 3'-terminal region of the gene encoding the hepatitis delta antigen (HDAg). We speculated that a peptide encoded by this ORF can be represented as the C-terminal domain of a new protein called HDAg'. This protein contains almost the entire sequence represented in the small form of HDAg and a peptide as an additional 'extension' sequence at the C-terminus. Two long synthetic peptides representing the two different types of peptides encoded by the small ORF were synthesized. These peptides were used for the development of an immunoassay for the detection of antibody to the HDAg' specific domain in sera of patients with HDV infection. Among 162 serum samples analyzed, 13 were found to be positive for an antibody reactive with these synthetic peptides. These antibodies were identified in patients with HDV infections and were not found in patients infected with hepatitis B virus, hepatitis C virus, or non-A,non-B,non-C virus. Thus, these data support the identification and existence of a new antigen encoded by the antigenomic RNA of the HDV. PMID- 8447180 TI - Cloning and sequence analysis of the coat protein gene of barley mild mosaic virus. AB - The sequence of the 3' 1462nts of RNA-1 of a UK isolate of the fungal-transmitted virus barley mild mosaic (BaMMV) has been determined. An open reading frame encoding the coat protein gene was identified within this region using amino acid sequence information obtained by cyanogen bromide cleavage of virus particles. The amino acid sequence of the full-length coat protein was deduced from the nucleotide sequence. Amino acid sequence comparisons revealed highest homology to the coat protein of barley yellow mosaic virus. In addition, a significant, but limited, number of the amino acid residues that are conserved between aphid transmitted potyviruses were also conserved between BaMMV and potyviruses. PMID- 8447181 TI - Are cardiac transplant recipients still suffering cardiac failure? PMID- 8447182 TI - Coronary heart disease deaths in 25 years. The experience in the three Serbian cohorts of the Seven Countries Study. AB - Three cohorts of men aged 40-59 at entry examination were enrolled between 1962 and 1964 in the Serbian section of the Seven Countries Study of Cardiovascular Diseases. They were a sample in the rural village of Velika Krsna (n = 511), the workers in an agro-industrial cooperative in the city of Zrenjanin (n = 516), and the University professors of Belgrade (n = 536). At entry examination and then after 5 and 10 years, some cardiovascular risk factors were measured while the follow-up for mortality and causes of death was continued for 25 years. The 25 year standardized death rates from coronary heart disease (CHD) were higher in Zrenjanin (177 per 1000) and lower in Belgrade (118) and Velika Krsna (122). The multivariate prediction of CHD mortality by the Cox model in the lumped samples showed significant coefficients for age, body mass index, systolic blood pressure and cigarette consumption. The coefficient of serum cholesterol did not reach a statistically significant level. An unknown but significantly protective factor was identified for the Belgrade sample, likely bound to the higher social class of this group. Changes of systolic blood pressure in the first 10 years of follow up were positively and highly related to the deaths occurred in the subsequent 15 years. The three population groups showed, between year 0 and year 10 follow-up, large increases in mean levels of blood pressure and mainly of serum cholesterol (+30 mg/dl in Velika Krsna; +36 mg/dl in Belgrade and +61 mg/dl in Zrenjanin). The sample in Zrenjanin started from intermediate levels (168.7 mg/dl) but attained the greatest increase and reached the highest CHD death rate in 25 years. PMID- 8447183 TI - The relative importance of myocardial energy metabolism compared with ischemic contracture in the determination of ischemic injury in isolated perfused rabbit hearts. PMID- 8447184 TI - Pacemaker current (i(f)) blockade causes heart rate reduction without negative inotropism: a new perspective in the treatment of ischemic heart disease. PMID- 8447185 TI - Role of fructose 2,6-bisphosphate in the control of glycolysis. Stimulation of glycogen synthesis by lactate in the isolated working rat heart. AB - Fructose 2,6-bisphosphate (Fru-2,6-P2) is the most potent stimulator of 6 phosphofructo-1-kinase (PFK-1), a key enzyme of glycolysis. We studied whether this regulator is involved in the changes of glycolysis that can be induced experimentally in the isolated working rat heart. The glycolytic flux was assessed by the rate of detritiation of [2-3H]- and [3-3H]glucose, by lactate output and by the changes in glycogen content. A 20-40% increase in Fru-2,6-P2 content was observed when glycolysis was stimulated by increasing either the workload (by increasing both preload and afterload) or the concentration of glucose (from 2 to 11 mM), or by adding 7 microM insulin. Anoxia decreased the external work developed by the heart, stimulated glycolysis by activating glycogenolysis, but did not increase Fru-2,6-P2. The increase of Fru-2,6-P2 content observed after insulin, high workload or glucose load might be related to a stimulation of glucose transport, and/or an activation of 6-phosphofructo-2 kinase (PFK-2), the enzyme responsible for the synthesis of Fru-2,6-P2. Addition to the perfusate of 0.5 to 10 mM lactate, which is a preferred substrate for the heart, with pyruvate in a 10:1 ratio, induced a dose-dependent inhibition of the glycolytic flux through PFK-1, with a maximal inhibition of 75% at 5 mM lactate. The accumulation of hexose 6-phosphates without change in fructose 1,6 bisphosphate and triose-phosphates concentrations confirmed that the inhibition of glycolysis was mainly exerted on PFK-1. This inhibition resulted from a doubling of the citrate concentration, an inhibitor, and from 75% decrease in Fru 2,6-P2. Despite the inhibition of glycolysis, glucose phosphorylation was barely affected by lactate, suggesting a change in glucose metabolism. Indeed, lactate induced a dose-dependent increase in glycogen content, which doubled at 5 mM lactate, reaching the level obtained after addition of 7 microM insulin. Increased glycogen synthesis was explained by the accumulation of UDP glucose, the substrate, and glucose 6-phosphate, a stimulator of glycogen synthase. We conclude that, during aerobiosis, Fru-2,6-P2 can be regarded as a glycolytic signal which is switched on by glucose availability, workload and insulin, and which is switched off by the availability of alternative oxidative substrates such as lactate. The latter also controls glucose metabolism by diverting glucose from glycolysis to glycogen synthesis. PMID- 8447186 TI - Association of a Wolff-Parkinson-White syndrome and a fistula from the coronary to the pulmonary artery. AB - We report the case history of a 52-year-old man with the Wolff-Parkinson-White syndrome and a fistula from the left anterior descending artery to the pulmonary artery. He had a left lateral bypass tract. To our knowledge, this is the first reported case of this association. Arterial malformations, along with vascular malformations of the coronary sinus, can be present in patients with a WPW syndrome. Coronary angiography with attention to the possible presence of arterial and venous malformations is indicated when atypical symptoms or signs are present in the WPW syndrome. PMID- 8447187 TI - 7th Annual Meeting of the B.W.G.I.C. Zaventem, December 4, 1992. Abstracts. PMID- 8447188 TI - Belgian Society of Cardiology, 12th annual meeting. February 4-6, 1993. Abstracts. PMID- 8447189 TI - Hormonal responses to the new potent GnRH antagonist Cetrorelix. AB - GnRH antagonists, unlike the GnRH agonists, immediately suppress gonadotropins and testosterone secretion without initial stimulatory effect. We report here on a single-dose study with the new GnRH antagonist Cetrorelix (Ac-D-Nal(2)1, D Phe(4C1)2, D-Pal3, D-Cit6, D-Alal0) in 25 normal men. The study involved five different dose groups (0.25, 0.5, 1.0, 1.5 or 3.0 mg) and subjects were observed over a 40 h period. Five men served as controls. Serum levels of LH, FSH and testosterone decreased rapidly with a dose-related decline for testosterone of 25%, 24%, 41%, 53% and 72%, respectively, for testosterone within the first 8 h of antagonist administration. All effects were reversible and no serious side effects were observed. Thus, this GnRH antagonist is active in men even in small doses and could become a new therapeutic tool for sex hormone-dependent diseases. Cetrorelix seems to have the highest suppressive rate per mg peptide of all other antagonists from the literature, such as Nal-Glu (Ac-D-Nal(2)1, D-Phe(4Cl)2, D Pal3, Arg5, D-Glu6(AA), D-Alal0), Detirelix (Ac-D-Nal(2)1, D-pCl-Phe2, D-Trp3, D hArg(Et2)6, D-Alal0) or 4F (Ac-delta 3Prol, 4F-D-Phe2, D-Trp3,6). During the time of suppression after a dose of 3 mg there was an LH and testosterone peak in the early morning coinciding with the testosterone peak in untreated men. The GnRH antagonist seems to unmask the circadian rhythm of LH secretion. PMID- 8447190 TI - The effect of growth hormone administration on testicular response during gonadotropin therapy in subjects with combined gonadotropin and growth hormone deficiencies. AB - To evaluate the effect of growth hormone on testicular response to human chorionic gonadotropins (hCG) in vivo in humans, we selected patients with combined deficits of GH and gonadotropins who were in substitution treatment with both GH (from the time of diagnosis) and gonadotropins (from the time of induction of puberty). Testicular response to gonadotropin therapy was then evaluated during and six months after the cessation of GH treatment. Blood samples were collected before and 2, 4 and 6 days after hCG administration. hCG responses were calculated and expressed as the areas under the response curve. We studied four hypogonadotropic patients (aged 18-19 years) with associated GH deficiency. Their gonadotropin treatment consisted of hCG 1,500 IU every six days, and FSH 75 IU every three days. The GH therapy replacement consisted of 4 IU thrice weekly. Testosterone, androstenedione, 17 alpha-hydroxyprogesterone and estradiol were measured. In all subjects the testosterone area during GH treatment was significantly higher compared to the testosterone area obtained without GH administration (2993 +/- 1091 vs 2310 +/- 751; M +/- SD; p < 0.04). The androstenedione area followed a similar pattern (708 +/- 377 vs 402 +/- 248; M +/- SD; p < 0.05). The 17 alpha-hydroxyprogesterone area, on the contrary, was significantly higher during GH withdrawal (542 +/- 307 vs 235 +/- 190; M +/- SD; p < 0.05). As far as the estradiol area is concerned, no significant differences were found (22,860 +/- 10,082 vs 25,697 +/- 13,640; M +/- SD). In conclusion, GH administration seems to improve testosterone production induced by human chorionic gonadotropins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447191 TI - Urinary excretion of GH in healthy individuals and patients with acromegaly, hypopituitarism and dwarfism. AB - Urinary GH excretion reflects average plasma levels. Using a highly sensitive sandwich enzyme immunoassay we determined GH concentrations in the 24 h accumulated urine samples of 54 healthy persons (aged 1.5-90 years), 8 acromegalic patients, 4 acromegalic patients after enucleation of a GH-producing adenoma, 8 patients with partial hypopituitarism and in first morning urine and 12 h accumulated daytime urine of 4 healthy children and 3 children with growth failure. GH secretion is age-dependent, with high rates between ages 1 and 20 (ages 0-20 years: 10.4 ng/g creatinine +/- 6.3 vs age > 20-75 years: 3.1 ng/g creatinine +/- 1.6). An age-dependent increase in urinary GH is found in the pubertal age group (10 ng/24 h +/- 6.8 vs prepubertal group: 4.6 ng/24 h +/- 2.95). GH excretion of patients with acromegaly differs significantly from healthy subjects (72 ng/24 h +/- 49 vs 3.9 ng/24 h +/- 2.3). After a successful operation, acromegalic patients do not differ from the collective norm. Six of 8 patients with partial hypopituitarism show lower GH concentrations in urine than healthy subjects (1.2 ng/l +/- 0.2 vs 2.6 ng/l +/- 1.2), but daily GH output does not differ, since significantly more urine is then excreted. At night, healthy children secrete significantly more GH than during the day (night: 0.16 ng.kg-1 x (12 h)-1 +/- 0.02 vs day: 0.07 ng.kg-1 x (12 h)-1 +/- 0.03), while output is the same for GH-deficient children. Both groups have similar GH daytime output, but GH-deficient children have significantly less nocturnal output.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447192 TI - Influence of smoking and snuff use on electrolytes, adrenal and calcium regulating hormones. AB - Little is known about the effects of snuff use on health. We have investigated electrolyte levels, adrenocortical and calcium regulating hormones in three groups of healthy young men, including 18 non-tobacco users, 21 snuff users and 19 smokers with similar age and body mass index. Smoking and snuff use was positively associated with alcohol and coffee consumption and inversely related to physical activity. Compared to non-tobacco users, smokers had significantly increased levels of serum sodium and magnesium, plasma calcitonin, urinary cortisol and potassium levels and decreased serum sex hormone-binding globulin as well as serum and urinary creatinine values. However, only decreased sexual hormone-binding globulin and urinary creatinine and increased serum phosphate and urinary potassium levels were seen in snuff users. Among tobacco users we noted that smokers differed from snuff users in that they had higher serum sodium (1.4 mmol/l, p < 0.01), plasma calcitonin (3.3 pmol/l, p < 0.05) and urinary cortisol (41 nmol/24 h, p < 0.05) but lower serum creatinine (5.8 mumol/l, p < 0.01). We conclude that chronic snuff use appears to have less influence on hormone and electrolyte balance than does smoking, and that some of the abnormalities seen in smokers do not seem to be mediated by nicotine. PMID- 8447193 TI - Glucocorticoids modulate the synthesis and expression of a 72 kDa heat shock protein in cultured Graves' retroocular fibroblasts. AB - Glucocorticoids modulate numerous proliferative, metabolic and immunological functions in human fibroblasts, some of which appear to be mediated via glucocorticoid receptors. We studied the influence of glucocorticosteroids on the synthesis and expression of a 72 kDa heat shock protein that is thought to play a role in thyroid autoimmunity. Experiments were performed using orbital fibroblasts derived from patients with Graves' ophthalmopathy and normal individuals. Cell monolayers were exposed to various concentrations of dexamethasone, the specific glucocorticoid agonist RU 28362, the glucocorticoid antagonist RU 38486, or combinations thereof, prior to heat stress or exposure to hydrogen peroxide. Heat shock protein 72 expression was assessed using sodium dodecylsulfate polyacrylamide-gel electrophoresis of cellular extracts, followed by autoradiography or immunoblotting with a mouse monoclonal antibody against the 72 kDa heat shock protein and quantitative scanning densitometry. In addition, cellular distribution of the immunoreactivity for the 72 kDa heat shock protein was studied using indirect immunofluorescence on parallel cultures. In other experiments, aimed at studying heat shock protein synthesis, cell cultures were pulse-labeled with [35S]-methionine prior to harvesting. Treatment with dexamethasone or RU 28362 markedly attenuated the heat stress-enhanced synthesis and expression of the 72 kDa heat shock protein and several other heat shock proteins both in normal and in Graves' retroocular fibroblasts (p < 0.001). In addition, either treatment reduced baseline expression of the 72 kDa heat shock protein in Graves' retroocular fibroblasts (p < 0.01). These effects were dose dependent and appeared to be mediated via the glucocorticoid receptor, because combined exposure to dexamethasone or RU 28362 plus RU 38486 completely restored synthesis and expression of the 72 kDa heat shock protein. Baseline or stress enhanced expression of the 72 kDa heat shock protein was not altered by treatment of monolayers with RU 38486 alone. As demonstrated by immunofluorescence, the characteristic intracellular shifting of the 72 kDa heat shock protein in response to cellular stress was partially inhibited by glucocorticoid agonists and restored by simultaneous exposure to glucocorticoid agonists and RU 38486. These results demonstrate that dexamethasone and the specific glucocorticoid agonist RU 28362 can modulate baseline- and stress-induced synthesis and expression of the 72 kDa heat shock protein, as well as its subcellular distribution, in cultured retroocular fibroblasts. Our studies suggest that these compounds exert these effects via the glucocorticoid receptor. PMID- 8447194 TI - Long-term follow-up in patients with autonomous thyroid adenoma. AB - A group of 375 untreated euthyroid patients with solitary autonomous adenoma of the thyroid were studied in a long-term follow-up (observation period 52.8 (mean)/46 (median), range 3-204 months). During the period of observation, 133 (34.2%) of all initially untreated patients underwent treatment (surgery, radioiodine, antithyroid medication) because of hyperthyroidism, mechanical problems, or at the patient's request. Sixty-seven patients developed hyperthyroidism resulting in a mean incidence of 4.1% per year. The incidence of hyperthyroidism increased during follow-up (3% in the first seven years, 10% in the following years). Age, sex, nodule size, initial scintigraphic appearance and the TRH test were of no individual prognostic value in predicting hyperthyroidism. Eleven of 14 patients with untreated hyperthyroidism became euthyroid without treatment during the time of follow-up. After iodine excess (by history or elevated iodine levels in urine, N = 45), 14 patients (31%) developed hyperthyroidism. In conclusion, we recommend a definitive treatment of autonomous adenoma at least in patients with advanced age, concomitant diseases and a higher probability of iodine exposure. PMID- 8447195 TI - Insulin-like growth factor I accelerates proliferation and differentiation of cartilage progenitor cells in cultures of neonatal mandibular condyles. AB - The present study examined the effect of exogenous IGF-I on growth and development of neonatal cartilage of the mandible condyle. Condylar cartilage was cultured as organ culture. The explants were cultured on top of collagen sponges in medium containing 2% fetal calf serum and were treated with IGF-I at doses ranging from 3.25 to 26 nmol/l for up to six days. IGF-I was found to increase significantly the uptake of [3H]-thymidine and [35S]-sulfate in a dose-related manner. The enhanced cellular proliferation, along with the increased synthesis of proteoglycans, resulted in a substantially larger mass of tissue in the organ culture system. The nature of the IGF-I stimulative effect was further studied through the use of a tissue culture system whereby a separated chondroprogenitor zone is cultured under conditions which favor its development at first into cartilage and then into bone. Using this culture system, we could show that IGF-I induces merely the de novo chondrogenesis process. This was reflected in the appearance of relatively large amounts of cartilage specific antigens such as type II collagen, cartilage proteoglycans, chondrocalcin and 100 KDa protein. Yet, no bone specific antigens were significantly increased, as is the case with GH effects. These results indicate that IGF-I is a strong chondrogenetic agent. But, unlike growth hormone, it does not seem to stimulate bone formation. PMID- 8447196 TI - Human placental lactogen directly inhibits rat cartilage growth processes in vivo and in vitro. AB - We have recently reported that human placental lactogen inhibits the growth of young female rats without changing the serum levels of insulin like growth factor I. Accordingly, experiments were conducted to determine whether human placental lactogen could directly inhibit cartilage growth processes in vivo and in vitro. Osmotic minipumps with attached polyethylene catheters were used to infuse the hormone for seven days into the left hindlimb of three-month-old female rats via the common iliac artery. The right hindlimb of each animal served as an internal control. Infusion of the placental lactogen at 10 micrograms/rat/day caused a slight (10%) but significant decrease in the width of the tibial epiphysial cartilage plate and a higher dose (100 micrograms/rat/day) caused a greater degree of inhibition (25%). However, the higher dose also inhibited the tibial cartilage plate of the contralateral (non-infused) limb. The possibility that human placental lactogen could directly inhibit cartilage anabolic activity in vitro was evaluated by measuring the incorporation of 35SO4 into costal cartilage explants from three to four-month-old female rats. The placental hormone inhibited the incorporation of 35SO4 in a dose-related manner at concentrations ranging from 1.0 to 100 micrograms/l. As a test of the specificity of this inhibition the effect of the hormone on the incorporation of 35SO4 into cartilage explants from Coho salmon was determined. The placental lactogen did not affect incorporation of the sulfate into the fish cartilage over a range of doses from 1.0 to 1000 micrograms/l.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447197 TI - Circulating levels and bone contents of bone gamma-carboxyglutamic acid containing protein in rat models of non-insulin-dependent diabetes mellitus. AB - In order to investigate the pathophysiology of the diabetic osteopenia observed in non-insulin-dependent diabetes mellitus, the circulating levels and the bone contents of bone gamma-carboxyglutamic acid-containing protein (osteocalcin) were determined in rat models of non-insulin-dependent diabetes mellitus, neonatally streptozotocin-induced rats and in genetic Wistar fatty rats. In Wistar fatty rats the plasma level of osteocalcin was 8.1 +/- 0.8 nmol/l, significantly lower than the value of 17.3 +/- 0.9 nmol/l in their lean littermates (p < 0.001). Bone length, bone strength, and weight of powdered bone in Wistar fatty rats were significantly decreased compared to control rats (p < 0.001, p < 0.02 and p < 0.001, respectively). Bone content of osteocalcin per femur in Wistar fatty rats was also significantly decreased compared to controls (p < 0.001). In addition, plasma osteocalcin in neonatally streptozotocin-induced diabetic rats was 2.9 +/- 0.3 nmol/l, which was also significantly decreased compared to the value of 5.6 +/- 0.5 nmol/l in their controls (p < 0.001). Since it has been established that the plasma level of osteocalcin is well related to bone formation and turnover, the low plasma values in these animal models suggest that bone formation and turnover are decreased in non-insulin-dependent diabetes mellitus. Low bone formation and turnover are, therefore, postulated to be one of the pathophysiological characteristics of the skeletal tissue in non-insulin dependent diabetes mellitus, and to be at least in part responsible for the occurrence of this complication. PMID- 8447198 TI - Thymostimulin effects on lymphoid organs in Ames dwarf mice. AB - This work was undertaken to study the effects of thymostimulin (TP-1) on the immune function in Ames dwarf mice, and to relate these effects to PRL and/or GH deficiency in these animals. Male Ames dwarf mice implanted with pituitaries from normal mice under the kidney capsule, sham-operated dwarf mice and normal immature or adult mice were injected daily for five days with TP-1. In comparison to normal animals, sham-operated dwarf mice had markedly lower body, thymus and spleen weights, as well as a lower number of lymphocytes in the spleen and in the thymus and the natural killer (NK) activity of spleen lymphocytes. Ectopic pituitary transplants produced the expected enhancement of body weight gain and increased spleen and thymus weights, which reached the values found in normal (non-dwarf) animals. The numbers of lymphocytes in the spleen and thymus were significantly increased in pituitary-grafted dwarf mice, but the grafts did not modify the cytotoxic activity of NK spleen cells, or the number of peripheral white blood cells (PWBC). In sham-operated dwarf mice, TP-1 treatment did not modify the number of cells in the spleen and thymus, or the NK activity. In pituitary-grafted dwarf mice, treatment with TP-1 induced an increase in the number of spleen lymphocytes and in the NK activity of spleen cells without affecting the weight of lymphoid organs or the number of thymic cells. Plasma prolactin (PRL) and growth hormone (GH) levels of pituitary-grafted dwarf mice were not changed after TP-1 administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447199 TI - Evaluation of acromegaly by measurement of 24-hourly urinary growth hormone excretion. AB - Twenty-four hourly urinary growth hormone excretion (24-h uGH) has been quantified using a combination of ultrafiltration and conventional immunoradiometric assay. Twenty-four hourly uGH was measured in 20 normal adults and in 42 patients with acromegaly (9 untreated, 28 treated but with above-normal IGF-I levels, and 5 treated and cured). The means and ranges were as follows: 3.7 (1-9) ng/24 h for normals and 160 (40-540), 66 (2-380) and 5.2 (4-8) ng/24 h for the three groups of acromegalic patients, respectively. Ten patients with pituitary adenomas without acromegaly had 24-h uGH within the normal range. Twenty-four hourly uGH therefore gives a clear differentiation between controls and untreated patients. Log-transformed values for subjects with acromegaly showed significant correlations between 24-h uGH and levels of IGF-I (r = 0.63, p < 0.01), fasting plasma GH (r = 0.92, p < 0.001) and plasma GH after glucose loading (r = 0.85, p < 0.001). Twenty-four hourly uGH was also determined in three acromegalic patients before and during SMS 201-995 therapy. Twenty-four hourly uGH reflected the corresponding changes in mean levels for hourly sampling over 12 h of plasma GH and IGF-I and in clinical signs after 3-6 months of therapy. The results of this study indicate that 24-h uGH is an accurate indicator of GH secretion in acromegalic patients and could therefore be used both in diagnosis and in monitoring the progress of therapy in these patients. PMID- 8447200 TI - Adrenaline and noradrenaline responses during insulin-induced hypoglycaemia in man: should the hormone levels be measured in arterialized venous blood? AB - To compare arterial, arterialized venous and venous measurements of plasma catecholamines during hypoglycaemia, six healthy men were studied by an iv infusion of insulin (1034 pmol.kg-1.h-1). Arterial blood glucose was clamped at the baseline level for the first 30 min and then reduced to 3.2 and to 2.5 mmol/l for 20 min subsequently. At each stage, arterial, arterialized venous and venous blood samples were simultaneously taken for analyses of plasma catecholamines. Plasma glucagon significantly declined during hyperinsulinaemic euglycaemia and then increased during hypoglycaemia. Plasma adrenaline and noradrenaline increased significantly during hypoglycaemia. During euglycaemia and mild hypoglycaemia, arterial adrenaline tended to be higher and arterial noradrenaline lower as compared with the corresponding arterialized and venous values. During marked hypoglycaemia, the arterial catecholamines were significantly higher than that of the two venous samples (p < 0.05). There was a significant correlation between the arterial and the arterialized as well as venous catecholamine values (p < 0.005). We conclude that, during euglycaemia and mild hypoglycaemia, the arterialized adrenaline values are closer to the arterial levels whereas the arterialized noradrenaline concentrations are similar to those measured in venous blood. However, during marked hypoglycaemia, both the arterialized adrenaline and noradrenaline are 20-30% lower than the arterial values, being close to the venous levels. PMID- 8447201 TI - Verapamil, a calcium channel blocker drug. PMID- 8447202 TI - Laboratory methods for detecting disseminated intravascular coagulation (DIC): new aspects. AB - The objective was to diagnose a hypercoagulative state or "pre-DIC" with new laboratory tests. APACHE II score was used as a measure of primary illness. Ventilator time was used as a reflexion of secondary complications. Twenty-three ICU patients were divided into two groups depending on time on the ventilator: Group 1 > 7 days and Group II < or = 7 days. If, after admittance patients deteriorated or complications occurred, new quantitative coagulation tests were done: soluble fibrin, prothrombin fragment 1 + 2, thrombin-antithrombin complex, D-dimer and elastase. We found a positive correlation between SF levels, the APACHE II score and the ventilator time. Diagnostic efficacy for SF was 87%, sensitivity 91%, specificity 83%, the predictive value of a positive result was 87% and the predictive value of a negative result 91%. The levels of the other new tests were also generally higher in the clinically worse group, although not significantly. Prothrombin complex, APTT, platelet count and AT III were pathologic to the same extent in both groups. The patients who developed most secondary complications, resulting in longer ventilator treatment (Group I), were also hypercoagulative. Soluble fibrin, in particular, seems to be valuable in the diagnosis of "pre-DIC" and possibly of predictive value for organ system complications. PMID- 8447203 TI - Contribution of rib cage and abdominal movement to ventilation for successful weaning from mechanical ventilation. AB - In order to test the hypothesis whether the breathing pattern is helpful in predicting weaning outcome in patients being weaned from mechanical ventilation, 38 patients who underwent operation for esophageal cancer were evaluated at weaning from mechanical ventilation (19 unsuccessful weanings, group U, and 19 successful weanings in age-matched patients, group S). Since all patients initially fulfilled our weaning criteria, ventilatory parameters such as tidal volume, respiratory frequency, minute ventilation, and arterial blood gas analysis showed no significant differences between the groups. The breathing pattern was registered quantitatively by means of respiratory inductive plethysmography at 3 cmH2O (0.3 kPa) of CPAP prior to weaning. The contribution of rib cage movement to tidal volume (%RC) was significantly greater in group U than in group S (P < 0.05). Indeed, 84% of the patients in group S showed %RC less than 50%, compared to only 16% of the patients in group U (P < 0.05). The results suggest that the breathing pattern is one important factor in predicting the outcome of weaning in patients after thoraco-abdominal surgery. Diaphragmatic fatigue is suspected to be the mechanism for the increase in the RC component in patients with unsuccessful weaning outcome. PMID- 8447204 TI - Effects of low-dose adenosine on myocardial performance after coronary artery bypass surgery. AB - The effect of a non-hypotensive dose of adenosine infusion on myocardial performance after coronary artery bypass surgery was examined. Upon arrival at the intensive care unit, 16 patients (14 males, 2 females; mean age 64.5, range 46-71) were randomized to a blinded infusion of either low-dose adenosine (n = 8) or placebo (n = 8). The infusion continued at a rate corresponding to 30 micrograms.kg-1.min-1 of adenosine into the right ventricle over 4 h. Data were collected from the arterial line, thermodilution pulmonary artery catheter, transoesophageal echocardiogram (TEE), and 12-lead ECG on six occasions: before infusion, hourly during the infusion, and 1 h after terminating the infusion. Mean arterial blood pressure did not differ between the adenosine and placebo groups at any measurement point. Heart rate increased by approximately 15% during the first hour of adenosine infusion. Cardiac index increased by approximately 50% during infusion of adenosine and cardiac index remained higher while systemic vascular resistance remained lower in the adenosine-treated group during infusion. The E/A ratio (ratio between peak left ventricular inflow blood velocities during early filling and atrial contraction) was significantly higher in the adenosine-treated group after treatment for 1 h while the area injection fraction did not differ between groups at any time. The number of patients with ischaemic events as judged from ECG and from left ventricular regional wall motion abnormalities (RWMA) as visualized by TEE did not differ between groups (ECG: one patient in the adenosine group and one patient in the placebo group RWMA: four patients in the adenosine group versus three in the placebo group).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447205 TI - Interpleural bupivacaine for analgesia during chest drainage treatment for pneumothorax. A randomized double-blind study. AB - The ability of interpleural analgesia to reduce the pain caused by an indwelling chest drain was evaluated in 22 patients treated for spontaneous pneumothorax. Intermittent 8-hourly bolus injections of 20 ml bupivacaine 0.5% with epinephrine were compared with placebo in a randomized double-blind fashion. Visual analogue pain scale (VAS) scores were registered after the 1st, 2nd, 4th, 7th and 10th injections. The scores were significantly lower in the bupivacaine group at 5, 15, 30 and 60 min after the first injection. No significant differences in pain scores were found after 4 or 8 h. Pain scores in the bupivacaine group were also reduced after the 2nd, 4th, 7th and 10th injections, but compared with placebo the differences were significant only after the 2nd and 7th injections. Parenteral morphine consumption was not significantly lower in the bupivacaine group. Arterial blood gases were unaffected by the treatment in both groups. It is concluded that interpleural analgesia using bupivacaine given as bolus injections at 8-h intervals significantly reduces the pain caused by a chest drain within 5 min of injection, but the duration of pain relief is less than 4 h. PMID- 8447206 TI - Hepatic disposition of sufentanil in patients undergoing coronary bypass surgery. AB - In order to clarify the relative contribution of the liver to the short-term disposition of sufentanil, hepatic blood flow was measured during induction of anaesthesia with a 10 micrograms/kg i.v. bolus dose of sufentanil followed by a continuous infusion of 0.3 microgram/kg/min of sufentanil. The hepatic clearance of the drug was 0.57 l/min after induction and 0.55 l/min at sternotomy, its hepatic extraction 92% and 91%, respectively. As a consequence of the high hepatic extraction, the hepatic clearance of sufentanil was closely dependent on hepatic plasma flow. Comparing the hepatic clearance of sufentanil with data from the literature for total body clearance of sufentanil, there is a significant difference of more than 0.3 l/min. It is concluded that there is evidence for a relevant extrahepatic disposition of sufentanil. PMID- 8447207 TI - Metabolic consequences of different perioperative fluid therapies in the neonatal period. AB - Carbohydrate and fat metabolism during and after anaesthesia and surgery was studied in 14 neonates with major congenital non-cardiac anomalies. They were either given a glucose solution until surgery or starved for at least 4 h before surgery. Ringer-acetate alone or Ringer-acetate plus 10% glucose was used for the intraoperative fluid therapy. After anaesthesia all neonates were given a 10% glucose solution. Concentrations of glucose, free fatty acids, triglycerides, lactate, pyruvate, alanine, glycerol and 3-hydroxybutyrate were measured at predetermined intervals pre-, intra- and postoperatively. Blood glucose concentrations rose during surgery both in neonates given glucose before and during surgery (n = 6) and in neonates not given glucose before and during surgery (n = 6). Increased intraoperative levels of free fatty acids and 3 hydroxybutyrate were found in neonates not given glucose before and during surgery. The triglyceride levels were equal in both groups. In two neonates given glucose before surgery and Ringer-acetate during surgery increased levels of 3 hydroxybutyrate were found, particularly in one patient who became hypoglycaemic. In conclusion, starved neonates without intraoperative glucose supply mobilized fat and maintained blood glucose concentrations. PMID- 8447209 TI - Doxapram improves pulmonary function after upper abdominal surgery. AB - The effects of doxapram on postoperative pulmonary function were studied in 40 ASA I and II patients randomly allocated to receive either doxapram 1.8 mg.kg-1.h 1 or placebo for 2 h immediately after elective cholecystectomy. The two groups displayed similar reductions of carbon dioxide production at 2 h and 6 h postoperatively, whereas oxygen consumption remained at preoperative levels for 24 h. Minute ventilation was similarly reduced in the two groups at 2 h and 6 h postoperatively, with corresponding increases in PaCO2. PaO2 was similarly and significantly decreased in both groups postoperatively, whereas P(A-a)O2 remained unchanged at 2 h and 6 h in doxapram-treated patients. FRC was reduced postoperatively in both groups, significantly more so in the control group at 6 h. Various indices of intrapulmonary gas distribution, including the functional (nitrogen) dead space, underwent similar changes in the two groups. By contrast, the physiological dead space was reduced in doxapram-treated patients at 2 h, 6 h and 24 h postoperatively, whereas no significant changes were seen in the control group. The ventilatory equivalent for CO2 was significantly lower in the doxapram treated group, implying higher ventilatory efficiency. Our findings indicate that infusion of doxapram postoperatively attenuates the impairment of pulmonary function postoperatively, chiefly via effects on V'A/Q' ratios. No side effects of doxapram were observed. PMID- 8447208 TI - Pharmacokinetics of sufentanil in general surgical patients under different conditions of anaesthesia. AB - The pharmacokinetics of sufentanil were studied in 56 surgical patients after an intravenous bolus of 2 micrograms kg-1, in association with neurolept analgesia or volatile anaesthetics (halothane, enflurane and isoflurane). Plasma concentrations of sufentanil were measured by radioimmunoassay. The kinetics of sufentanil were comparable under neurolept analgesia and under anaesthesia with halothane, enflurane or isoflurane. The overall mean elimination half-life was 182 min, Vdss 169 l and the plasma clearance 910 ml min-1. Except for the isoflurane subgroup, there was no significant correlation between half-life, the volume of distribution or clearance with age (24-77 years) or body weight (45-95 kg). PMID- 8447210 TI - Comparison of P6 acupoint injection with 50% glucose in water and intravenous droperidol for prevention of vomiting after gynecological laparoscopy. AB - Postoperative vomiting causes patients distress and delays discharge after outpatient surgery. Although P6 electroacupuncture is recognized as having an antiemetic effect, its inconvenient instrumentation may limit its clinical applicability. The purpose of this study was to explore a simple and effective alternative method for control of postoperative vomiting in outpatient surgery. We prospectively compared the effect of P6 acupoint injection with 0.2 ml 50% glucose in water (G/W) and intravenous injection of 20 micrograms/kg droperidol for prevention of vomiting in 120 consecutive outpatients undergoing gynecological laparoscopy with general anesthesia. Patients were randomly allocated to receive P6 acupoint injection, i.v. droperidol, or nothing as control group. Both P6 acupoint injection and i.v. droperidol 20 micrograms/kg were found to have a significant antiemetic effect when compared with the control group. We conclude that P6 acupoint injection with 50% G/W is a simple and effective method for reducing the incidence of postoperative emesis in outpatient surgery. PMID- 8447211 TI - Oesophageal thermal tube for intraoperative hypothermia in liver transplantation. AB - In order to prevent the occurrence of major hypothermia during liver transplantation, with its deleterious effects on intraoperative cardiovascular activity and on postoperative graft functioning, this study evaluated the benefit of an oesophageal rewarmer, used during surgery, in addition to the usual methods of warming (OR temperature at 22 degrees C, rewarming of fluids and blood, heating mattress, heat and moisture exchanger). We compared 10 patients with an oesophageal rewarmer (OeR group) to 10 patients without (Control group). The anaesthetic procedure was similar in all cases. Rectal (RT) and pulmonary artery (PT) temperatures were recorded during the three phases of surgery (pre anhepatic, anhepatic, postanhepatic phase) and their time course was analysed with non-parametric tests. The two groups were comparable with regard to duration of surgery, blood and fluid requirements and veno-venous bypass flow rate. The RT decreased similarly in both groups, but was significantly higher in the OeR group at peritoneum closure (P < 0.01). The PT was higher in the OeR group after onset of venous shunting (P < 0.05) and during the third phase of surgery (P < 0.01). Three incidents (one leakage and two herniations of the latex tube) occurred, without detrimental effects on the patients. It is concluded that the oesophageal heat exchanger allows better rewarming after revascularization of the graft, but is unable to prevent cardiac hypothermia at unclamping. PMID- 8447212 TI - Evaluation of myocardial contractility in the chronically instrumented dog with intact autonomic nervous system function: effects of desflurane and isoflurane. AB - Characterization of changes in myocardial contractility using indices derived from ventricular pressure-segment length loops in animals with intact autonomic nervous system (ANS) function is complicated by alterations in systemic hemodynamics mediated by baroreceptor reflexes and by spontaneous respiration and its effects on ventricular pressure and filling. This investigation examined and compared the effects of desflurane and isoflurane on myocardial contractility in dogs with intact ANS reflexes using techniques designed to overcome these potential difficulties. Two groups comprising 18 experiments were performed using nine dogs chronically instrumented for measurement of aortic and left ventricular pressure, the maximum rate of increase of left ventricular pressure (dP/dt), subendocardial segment length, cardiac output and intrathoracic pressure. A brief occlusion of the inferior vena cava was used to alter preload to generate pressure-length loops prior to onset of baroreceptor reflex-mediated increases in heart rate. Respiratory variation in ventricular pressure was negated by calculation of "transmural pressure" via instantaneous subtraction of intrathoracic pressure from corresponding left ventricular pressure. Contractility was then evaluated in the conscious and anesthetized states using transmural pressure-length loops and calculation of the preload recruitable stroke work (PRSW) relationship. Dogs were anesthetized with 1.25, 1.5, or 1.75 MAC desflurane or isoflurane and measurements were repeated after 30 min of equilibration at each anesthetic concentration. Desflurane and isoflurane produced similar declines in PRSW slope [Mw; 41 +/- 6 (5.5 +/- 0.8) during 1.75 MAC desflurane compared to 43 +/- 5 mmHg (5.7 +/- 0.7 kPa) during 1.75 MAC isoflurane], indicating that these agents cause similar depression of contractile state at equivalent MAC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447213 TI - Cerebral pharmacodynamics of anaesthetic and subanaesthetic doses of ketamine in the normoventilated pig. AB - There are still divergent opinions regarding the pharmacodynamic effects of ketamine on the brain. In this study, the cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2) and electroencephalographic (EEG) activity were sequentially assessed over 80 min in 17 normoventilated pigs following rapid i.v. infusions of anaesthetic (10.0 mg.kg-1; n = 7) or subanaesthetic (2.0 mg.kg-1; n = 7) doses of ketamine or of its major metabolite norketamine (10.0 mg.kg-1; n = 3). The animals were continuously anaesthetized with fentanyl, nitrous oxide and pancuronium. CBF was determined by the intra-arterial 133Xe technique. Ketamine (10.0 mg.kg-1) induced an instant, gradually reverting decrease in CBF, amounting to -26% (P < 0.01) at 1 min and -13% (P < 0.05) at 10 min, a delayed increase in CMRO2 by 42% (P < 0.01) at 10 min and a sustained rise in low- and intermediate frequency EEG voltage by 87% at 1 and 97% at 10 min (P < 0.0001). It is concluded that metabolically formed norketamine does not contribute to these effects. Considering the dissociation of CBF from CMRO2 found 10-20 min after ketamine (10.0 mg.kg-1) administration, it is suggested that ketamine should be used with caution for anaesthesia in patients with suspected cerebral ischaemia in order not to increase the vulnerability of brain tissue to hypoxic injury. Ketamine (2.0 mg.kg-1) had no significant effects on CBF, CMRO2 or EEG. It therefore seems that up to one fifth of the minimal anaesthetic i.v. dose can be used safely for analgesia, provided that normocapnaemia is preserved. PMID- 8447214 TI - The effects of amrinone and calcium chloride on pulmonary vasculature and biventricular function in ethchlorvynol-induced lung injury in sheep. AB - The effects of amrinone and CaCl2 on pulmonary vasculature and biventricular function in sheep with acute lung injury (ALI) were studied. Seven sheep were ventilated with a tidal volume of 10-12 ml.kg-1 with end-tidal CO2 of 40 +/- 5 mmHg (5.3 +/- 0.7 kPa) after acute lung injury was induced with up to 30 mg kg-1 of ethchlorvynol (ECV). Biventricular function and hemodynamic profiles were estimated with a rapid computerized thermodilution method and modified pulmonary artery catheters after acute lung injury, following a loading dose (1 mg kg-1) and maintenance dose (5 micrograms kg-1 min-1) of amrinone and after a bolus dose of CaCl2 (20 mg kg-1). ECV successfully induced acute lung damage in sheep, causing significant increases in pulmonary artery pressure (PAP) and pulmonary vascular resistance index (PVRI). Amrinone reversed the unfavorable changes induced by ECV, significantly reducing PAP, PVRI and left ventricular end diastolic volume (LVEDV). CaCl2, however, reversed the effect of amrinone and increased PAP, PVRI, and LVEDV but decreased left ventricular ejection fraction. PMID- 8447215 TI - Intrathecal morphine for the relief of post-hysterectomy pain--a double-blind, dose-response study. AB - Eighty patients undergoing total abdominal hysterectomy under general anaesthesia were randomly divided into four groups to study the dose-response relationship of intrathecal morphine (0, 0.1, 0.3 and 0.5 mg) for postoperative pain relief. Pain scores, as assessed by using the visual analogue scale, revealed that intrathecal morphine provided long-lasting pain relief, was most effective after 0.3 mg and significantly reduced the need for supplementary analgesics (P < 0.05). There was no difference as regards the quality of analgesia or the use of supplementary analgesics between the 0.3 and 0.5 mg groups. Adequate pain relief was not evident after a 0.1 mg dose. There was no incidence of respiratory depression in any of the patients in this study. The incidence of side effects was least following 0.3 mg intrathecal morphine, which we consider to be the optimum dose. PMID- 8447216 TI - Pregnancy outcome in an extremely small woman with muscular dystrophy and respiratory insufficiency. AB - Throughout her pregnancy and delivery, we followed a tiny 32-year-old woman suffering from muscular dystrophy and respiratory insufficiency. With carefully monitored maternal and fetal oxygenation and planned cesarean section under combined epidural and general anesthesia, she delivered a healthy baby at 32 gestational weeks. PMID- 8447217 TI - 13 Years of the Department of Otorhinolaryngology, Osaka University Medical School. Scientific papers dedicated to Professor Toru Matsunaga, Chairman, in commemoration of his retirement. PMID- 8447218 TI - Neuropharmacology of motion sickness and emesis. A review. AB - Histamine H1-receptors are involved in the development of the symptoms and signs of motion sickness, including emesis. On provocative motion stimulus, a signal for sensory conflict activates the histaminergic neuron system, and the histaminergic descending impulse stimulates H1-receptors in the emetic center of the brain stem. The histaminergic input to the emetic center through H1-receptors is independent of dopamine D2-receptors in the chemoreceptor trigger zone and serotonin 5HT3-receptors in the visceral afferent, which are also involved in the emetic reflex. Antihistamines block emetic H1-receptors to prevent motion sickness. Acetylcholine muscarinic receptors are involved in the generation of signals for sensory conflict. Anti-cholinergic drugs prevent motion sickness by modifying the neural store to facilitate the acquisition of habituation to provocative motion. PMID- 8447219 TI - Reduction of leaky lymphocyte clones producing immunoglobulins and thymic lymphocytic leukemia by selective inbreeding of SCID (severe combined immunodeficiency) mice. AB - Selective inbreeding of C.B17-scid/scid mouse pairs showing undetectable IgG and IgM has been carried out in order to reduce the mortality of mice by early occurrence of thymic lymphocytic leukemia and abnormal lymphocyte clones producing immunoglobulins, both of which inhibit the successful heterotransplantation of normal and neoplastic human tissues. Although the majority of C.B17-scid/scid mice showed undetectable (< 1 microgram/ml) or low level (< or = 25 micrograms/ml) of serum IgG and IgM, some produced abnormally high concentrations of IgG and IgM (> 25 micrograms/ml). The incidence of such mice showing higher levels of IgG was very high at F1 and F2 generation (10/55, 18.2%), but significantly low after the F3 generation (18/446, 4.0%, p << 0.001). Although leukemia incidence was very high at F4 to F5 generations (8/40, 20.0%), death from leukemia was not observed early in life (4-6 months after birth) at F7 to F10 generations (0/36, 0%, p < 0.01) and was very low during the age of 6-10 months after the F8 generation (11/66, 16.7% at F4 and F5 vs 4/93, 4.3% at F8 10), p < 0.01). Scid mice improved by the selective inbreeding will provide an invaluable experimental system for the heterotransplantation of normal and neoplastic human tissues. PMID- 8447220 TI - Calcitonin gene-related peptide in the efferent system of the inner ear. A review. AB - Many calcitonin gene-related peptide-like immunoreactive (CGRP-IR) fibers were found in the vestibular end-organs and the cochlea of rats. CGRP-IR fibers in the vestibular end-organs originated in the bilateral cell groups dorsolateral to the genu of the facial nerve. These fibers formed a fiber plexus at the base of the sensory epithelia in the maculae of the otolith organs and the ampullae of the semicircular canals, and formed synaptic contacts with the nerve chalice on type I vestibular sensory cells. CGRP-IR fibers in the cochlea originated in the ipsilateral lateral superior olivary nucleus. Most of them existed in the inner spiral bundle under the inner hair cells, and formed synaptic contacts with afferent terminals on the inner hair cells. These findings suggest a postsynaptic modulation of CGRP on the vestibular and cochlear information at the level of type I vestibular sensory cells and the inner hair cells. PMID- 8447221 TI - Analysis of head and body movements of elderly people during locomotion. AB - In order to elucidate the effect of aging on head and limb motions, 10 young and 8 elderly normal subjects were studied kinesiologically during i) walking, ii) stepping, and iii) hopping, with their eyes open or closed. For this study, a 16 mm high-speed cinecamera and accelerometers were used. Analysis of head movements showed that pitch rotation seemed to counteract the translational movement in the sagittal plane. Although this phenomenon was observed in both the young and elderly groups, the mean pitch position of the head, as measured by the cantho meatal line relative to the horizontal line, was larger for the elderly group, while head acceleration of elderly people showed a higher frequency in the power spectrum. With eyes closed, the head tended to be tilted downward. PMID- 8447222 TI - Motion sickness induced by sinusoidal linear acceleration in rats. AB - The characteristics of linear acceleration to cause motion sickness of rats were examined using pica as a behavioral index of motion sickness. A vestibular sled was used to generate sinusoidal linear acceleration. At 0.4 Hz and with a peak acceleration of 0.15 G, the effectiveness of linear acceleration in inducing motion sickness was X-axis > Y-axis > Z-axis. At 0.4 Hz and along the X-axis, rats suffered from more severe motion sickness with a high peak G load (0.15 G) than with a low one (0.08 G). Along the X-axis and with a peak acceleration of 0.15 G, the severity of motion sickness was not related to frequency (0.4, 0.6 Hz). PMID- 8447223 TI - Nystagmus responses in normal subjects during eccentric sinusoidal rotation. AB - Earth vertical axis rotation provides a method of stimulating the horizontal semicircular canals. By placing subjects off from the axis of rotation, the otolith organs may also be stimulated by additional linear acceleration forces. In the present study, we compared the rotation with subjects placed on axis to those placed in an eccentric position, either facing outward or turned 90 degrees facing the direction of the rotation. When the subject was facing outward, sinusoidal eccentric rotation at 0.64 Hz produced a significantly higher vestibulo-ocular reflex (VOR) gain than did on-axis rotation. No increase in VOR gain was observed during eccentric rotation with the subject facing the direction of the rotation. These findings suggest that the gain enhancement due to eccentric rotation is a result of tangential linear acceleration, probably sensed by the utriculus. This study raises the possibility of using eccentric rotation for the diagnosis of the patients with otolith dysfunction. PMID- 8447224 TI - Effect of changes in blood pressure on per-rotational nystagmus in guinea pigs with obliterated endolymphatic sac. AB - The effect of blood pressure (BP) changes on per-rotational nystagmus (PRN) was compared between normal guinea pigs and guinea pigs with unilaterally obliterated endolymphatic sac. Eye movements were recorded 3 months postoperatively. When the animal was rotated sinusoidally, asymmetry of PRN was minimal in the control animals. In the operated guinea pigs, however, nystagmus oscillating toward the operated side was largely suppressed when BP was decreased (30-40 mmHg). Thus, directional preponderance of PRN toward the nonoperated side was established. Oxygen tension (pO2) was measured in the perilymphatic space of the lateral semicircular canal to investigate the mechanisms underlying the PRN asymmetry. When BP was reduced below normal, pO2 on the operated side decreased much more than that on the intact side. It is suggested that obliteration of the endolymphatic sac results in an autoregulatory dysfunction in the semicircular canal. Asymmetry of the vestibulo-oculomotor reflex at low BP may be the result of decreased blood flow to the semicircular canal. PMID- 8447225 TI - Hearing recovery following large and small fenestra stapes surgery for otosclerosis. AB - Fifty-five ear of 49 patients with otosclerosis were operated on with either large fenestra stapes (stapedectomy; SDE) or small fenestra stapes (stapedectomy; STO) surgery. Pre-operative average hearing levels for the speech frequency ranges (0.5, 1, 2 kHz) were 56.1 dBHL for SDE and 61.0 dBHL for STO. These improved to 39.0 dBHL and 35.0 dBHL. Statistically, significant hearing recovery was obtained for a frequency range from 0.125 to 2 kHz for SDE and from 0.125 to 4 kHz for STO (p < 0.05, Dunnett's multiple variance test). The degree of post operative hearing improvement for STO was significantly higher at 0.5, 2 and 8 kHz than that for SDE (p < 0.05, Student's t-test). A pre-operative speech discrimination score of 80% was obtained at 68.9 dB for SDE and at 76.0 dB for STO. These values improved to 56.1 dB and 49.5 dB post-operatively. Thus, it was proved that STO results in better hearing than SDE does. PMID- 8447226 TI - The role of summating potential in the diagnosis and management of Meniere's disease. AB - To assess the role of a negative summating potential (-SP) in the clinical diagnosis and management of Meniere's disease, the relationship of -SP abnormality to clinical symptoms, hearing level and caloric test results was examined in 70 patients with unilateral Meniere's disease. The click-induced -SP and action potential (AP) were recorded by extratympanic electrocochleography. When SP/AP ratio exceeded 0.43, the -SP was considered to be abnormal. No significant relationship was found between abnormal -SP and clinical symptoms (the duration of cochlear and vestibular symptoms, recent hearing fluctuation and recent vertigo attack). Ears with abnormal -SP had a significantly worse hearing loss at high frequencies (2-8 kHz) than ears with normal -SP, whereas there was no significant difference in hearing loss at low frequencies (0.25-1 kHz) between both ears. No significant relation was found between abnormal -SP and abnormal unilateral weakness in caloric test. The results indicate that the click-induced SP reflects the pathophysiology of Meniere's disease basically in the cochlear partition at high frequencies. PMID- 8447227 TI - Tinnitus suppression by electrical promontory stimulation in sensorineural deaf patients. AB - In 62 patients, whose hearing acuity was normal or profoundly impaired, tinnitus suppression was attempted through electrical promontory stimulation (EPS) with a Promontory Stimulator (Cochlear Co.). The causes of tinnitus were idiopathic sudden deafness, ototoxicity, noise induced hearing loss, labyrinthitis, Meniere's disease, acoustic neuroma and unknown origin. Reduction of tinnitus was achieved in 46 of 68 ears (67.6%). Of these, EPS was most effective in cases of noise induced hearing loss (100.0%; 3/3), followed by those of idiopathic sudden deafness (87.5%; 14/16), Meniere's disease (83.3%; 5/6), labyrinthitis (75.0%; 6/8), ototoxicity (66.6%; 4/6) and unknown origin (76.4%; 13/17). The treatment had hardly any effect on patients with acoustic neuroma (8.3%; 1/12). Twenty patients reported residual inhibition with a duration ranging from several hours to one week. Our results suggest that tinnitus due to cochlear lesions can be suppressed by EPS. This technique may also be useful for differentiation between tinnitus resulting from cochlear lesions and from retrocochlear lesions. PMID- 8447228 TI - Sonotubometry with a tubal catheter as an index for the use of a ventilation tube in otitis media with effusion. AB - Insertion of a ventilation tube is considered to be an effective treatment for otitis media with effusion (OME), although it may entail complications such as residual perforation and poor hearing after tube extrusion. In order to reduce problems associated with ventilation tubes, we examined the Eustachian tube function in 25 adults with OME by two methods. One was a sonotubometric measurement (sonotubometry) with both a tubal catheter and a nasal olive tip, and the other was an air-pressure equilization method (deflation test). Sixty percent of the ears showed poor tubal function in both types of sonotubometry. The number of negative cases in sonotubometry with a tubal catheter was higher in ears with a larger volume of effusion, and in ears with poor tubal function by deflation testing. Judging from the volume of effusion and results of the deflation tests, the prognosis could be fairly good in many positive cases. We conclude that sonotubometry with a tubal catheter is useful in the management of OME, especially in evaluating the efficacy of ventilation tubes. PMID- 8447229 TI - The ultrastructure of the basilar papilla of the budgerigar's inner ear. AB - The basilar papilla in the inner ear of the adult budgerigar was studied by scanning and transmission electron microscopy. The sickle-shaped basilar papilla has short hair bundles on the proximal tip and long ones on the distal tip. The tectorial membrane shows a honeycomb-like pattern and enclosed a hair bundle in its alveolus. The papilla consists of two different types of hair cells; short and tall hair cells. The short hair cells with large efferent nerve endings are located on the free basilar membrane in the inferior part. The tall hair cells with large afferent nerve endings are located in the superior part. The similarity and difference of the structure are discussed between the budgerigar and other birds, and between birds and mammals. PMID- 8447230 TI - Electron microscopical observations of melanin in the endolymphatic sac. AB - Endolymphatic sacs of pigmented guinea pigs were examined by light and electron microscopy. Melanocytes were located not only in the subepithelial connective tissue but also in the intercellular spaces between the epithelial cells. They projected their dendrites into the epithelium extensively. Melanosomes in several stages of maturation and well-developed Golgi apparatus were seen in the cytoplasm of the melanocytes. Melanosomes were also observed in the membrane bound vacuoles of the epithelial cells. These findings suggest that melanocytes in the endolymphatic sac are highly capable of producing tyrosinase, synthesizing melanin and transferring melanosomes to the epithelial cells, while melanocytes in the other parts of the inner ear do not show signs of melanogenesis under normal conditions. PMID- 8447231 TI - Effects of adenylate cyclase activation on electrical resistance of scala media. AB - Electrical resistance of scala media at the second turn of the guinea pig cochlea was measured while cochlear adenylate cyclase was activated by perilymphatic perfusion with 2 x 10(-4) M forskolin. The electrical resistance decreased from the pre-forskolin value (6.36 +/- 0.27 k omega to 5.22 +/- 0.33 k omega, n = 5), while the endocochlear potential (EP) increased from the pre-forskolin value (70.2 +/- 2.1 mV to 81.2 +/- 2.8 mV, n = 5). The time course of the electrical resistance change was more rapid than that of the EP change but almost identical to the time course of the change in the Cl- activity of the endolymph. The results suggest that the forskolin-induced decrease in the electrical resistance of the perilymph-endolymph barrier (presumably Reissner's membrane), and the consequent increase in Cl- flux into the endolymph may trigger EP elevation. PMID- 8447232 TI - GAP-43 mRNA expression in facial motoneurons during regeneration: in situ hybridization histochemistry study using an alkaline phosphatase-labelled probe. AB - By means of in situ hybridization histochemistry using an alkaline phosphatase labelled probe, we found an increase of mRNA for the growth-associated protein GAP-43 in rat facial motoneurons following axotomy of the facial nerve. After nerve resection, the increased level of GAP-43 mRNA was maintained for at least 8 weeks, while it returned to almost undetectable levels by 8 weeks after nerve crush injury. Thus, expression of GAP-43 mRNA in motor neurons paralleled the process of axonal regeneration. However, the increase of GAP-43 mRNA after resection was more pronounced than after crushing, in this way being different from the pattern of low-affinity nerve growth factor receptor mRNA expression. PMID- 8447233 TI - Measurement of anaphylatoxin activity during surgery. AB - We studied whether or not anaphylatoxins (ATs) are related to stress-related surgery by examining AT measurement in 51 patients undergoing operation. C3a plasma levels in patients who underwent the Caldwell-Luc operation increased from a pre-surgery concentration of 129 +/- 19 (mean +/- SD) ng/ml to 293 +/- 91 ng/ml during surgery under local anesthesia. However, pre- and post-surgery values were almost the same. No significant change occurred in the C5a plasma concentration at any time in patients undergoing the Caldwell-Luc operation, tonsillectomy or partial glossectomy. The mechanism underlying elevation in C3a during surgery is discussed. PMID- 8447234 TI - Five cases of mucormycosis in paranasal sinuses. AB - Five cases of mucormycosis are reported, 2 of them suffered from immunosuppression, the other 3 did not. We conclude that a combination of CT and bacteriological findings is useful for the diagnosis of mucormycosis differentially from other diseases. Therapy consisted of paranasal debridement and administration of amphotericin B. PMID- 8447235 TI - Antidepressant response to sleep deprivation as a function of time into depressive episode in rapidly cycling bipolar patients. AB - Three patients with treatment-resistant rapidly cycling bipolar disorder were studied with multiple sleep deprivations (SD) during several depressive episodes to assess the effect of phase or duration of a depressive episode on SD response. There was little response to SD early in a depressive episode, but responses were often robust late in an episode, sometimes triggering its termination. In 2 subjects, the duration of antidepressant response to SD increased linearly as time into episode increased. Neither the number of SD given in an episode nor the medication status of the patients appeared to account for the observed increases in antidepressant response. These results suggest that the neurobiological substrates underlying depression may change over the course of an episode, resulting in an increased responsivity to sleep deprivation later compared with earlier in the course of an episode in rapidly cycling patients. The generalizability of these findings to unipolar patients remains to be explored. PMID- 8447236 TI - A unique monthly distribution of suicide and parasuicide through firearms among Israeli soldiers. AB - The monthly distribution of completed suicide and parasuicide by Israeli soldiers was analyzed during the 7-year period of 1984-1990. Although parasuicide in general showed a constant incidence throughout the year, the monthly rate of suicide as well as parasuicide through firearms varied during the year in a similar way. The seasonal pattern of completed suicides, the vast majority of which occur with firearms, was correlated with the seasonal pattern of parasuicides through firearms. The combined variability of the two seasonal patterns was found to be significantly different from a pattern of a constant monthly incidence with a peak in December and a nadir in October. The monthly incidence of suicide and parasuicide through firearms was found to be negatively correlated with the duration of the daily photoperiod, when the latter was phase advanced by 1-2 months. This unique pattern of seasonal incidence of suicide and parasuicide through firearms is different from most of the patterns reported in the Northern Hemisphere. PMID- 8447237 TI - A long-term study of remoxipride in chronic schizophrenic patients. AB - The purpose of this study was to assess the tolerability and efficacy of 150-600 mg remoxipride (predominantly a DA2 receptor antagonist) in an open long-term (1 year) multicentre trial in chronic schizophrenic patients. The mean duration of illness before entering the study was 21 years and the pre-study neuroleptic dosage in chlorpromazine equivalents was 930 mg/day. The clinical efficacy was measured with the Brief Psychiatric Rating Scale and the Clinical Global Impression scale. The adverse events were recorded by a 26-item Adverse Symptom Checklist and by the Abnormal Involuntary Movements Scale. Forty-five patients were included in the study. The mean daily dose of remoxipride during the last week of treatment was 378 mg. Eighty percent (36 patients) withdrew prematurely (< 1 year). The main reasons for withdrawal were: ineffectiveness (n = 15), treatment refusal (n = 12) and adverse events (n = 8). The most frequently reported adverse events were insomnia (n = 20) and tiredness (n = 7), whereas only a few (n = 6) extrapyramidal symptoms were reported. There was no relationship between remoxipride plasma concentration and clinical efficacy nor was any relationship found between the ratio of pretrial chlorpromazine equivalent to last remoxipride dose and the therapeutic effect. Remoxipride alone seemed to have an insufficient neuroleptic efficacy in these chronic and treatment-resistant schizophrenic patients but was well tolerated. PMID- 8447238 TI - The validity of diagnoses obtained through the psychological autopsy procedure in adolescent suicide victims: use of family history. AB - A test of validity of the psychiatric diagnoses obtained by the psychological autopsy procedure is described in a consecutive series of 67 adolescent suicide victims. Family history of mental illness in first-degree relatives of subjects was obtained blind to subject diagnosis using the family history method. It was hypothesized that subjects with a given diagnosis, compared with subjects without this diagnosis, would show an increased rate of this disorder among first-degree relatives. This hypothesis was supported insofar as specific associations between subject diagnosis and familial rates of illness were demonstrated for major depression, bipolar illness, conduct and antisocial disorder and substance abuse. These results provide further support for the validity of diagnoses obtained through the psychological autopsy procedure. PMID- 8447239 TI - Delirium and dementia in acute medical admissions of elderly patients in Iceland. AB - A prospective study was carried out in a general hospital in Reykjavik to evaluate the prevalence of delirium and dementia among 331 patients 70 years and older who were admitted as an emergency to the medical department. Cognitive function was screened with Mental Status Questionnaire (MSQ) and Mini-Mental State Examination (MMSE) and diagnosed according to DSM-III-R for delirium and dementia. Other information obtained included social and demographic factors, drug consumption, the main condition underlying the delirium and outcome. Severe cognitive dysfunction was present in 32% of all acutely admitted patients 70 years and older, which were diagnosed further as delirium 14% and dementia 18%. At follow-up, concurrent dementia was found in 70% of the delirium patients. The main causes for delirium were cardiac failure 27%, stroke 22% and sepsis 16% and the mortality rate was 32% compared with 8% in dementia alone. The prognosis of patients with delirium and dementia depends on detecting these disorders, and the clinical skills of physicians working with acutely ill elderly patients can be improved by relatively simple screening questionnaires such as the MSQ and MMSE. PMID- 8447240 TI - Agreement in psychiatric assessment. AB - In 103 schizophrenic patients we investigated the extent of practice needed in the use of the Brief Psychiatric Rating Scale (BPRS) to enable its reliability to be assessed. The agreement level of the 7 raters was analysed. Generally, the lowest mean agreement found was for the negative symptoms of the BPRS schizophrenia subscale. A high degree of agreement was attained both for the positive symptoms of the BPRS schizophrenia subscale and for the symptoms of the depression--and of the mania subscale. The degree of disagreement observed was due to both individual differences in assessment ability and the rating procedure. These results indicate that it is necessary to state the degree of agreement achieved in studies in which several raters are taking part. PMID- 8447241 TI - A double-blind, comparative, multicentre study comparing paroxetine with fluoxetine in depressed patients. AB - A randomized, double-blind, parallel-group, 6-week study was undertaken to compare the efficacy and tolerability of once or twice daily administration of the selective serotonin reuptake inhibitors paroxetine and fluoxetine. After a 1 week placebo wash-out, patients suffering from DSM-III major depression and with a score of 18 or more on the 21-item Hamilton Rating Scale for Depression (HRSD) received either paroxetine or fluoxetine. The patients were assessed for efficacy using the HRSD, Montgomery-Asberg Depression Rating Scale and Clinical Global Impression; for tolerability, adverse events were elicited by the use of a non leading question and a side effects checklist. The groups of patients were comparable on entry to the study. One hundred patients were recruited into the study, of whom 78 were evaluable for the efficacy analysis. Paroxetine and fluoxetine showed comparable efficacy at the end of the 6-week treatment period, but a statistically significant difference in the number of responders at week 3 in favour of paroxetine was observed. This could suggest an earlier onset of action with paroxetine. Also, associated anxiety symptoms were significantly reduced on paroxetine compared with fluoxetine at week 3. Patients on paroxetine reported fewer adverse events than those on fluoxetine. The most commonly reported adverse events were nausea and vomiting in both groups. PMID- 8447242 TI - The Canberra Interview for the Elderly: assessment of its validity in the diagnosis of dementia and depression. AB - The Canberra Interview for the Elderly (CIE) has been developed as a field instrument for identifying cases of dementia and depression, according to the diagnostic criteria in both draft ICD-10 and DSM-III-R. It has been designed to be administered by lay interviewers and responses are assembled algorithmically to derive diagnoses. The validity of the CIE was assessed using a sample of 75 elderly patients attending a hospital clinic. The CIE diagnoses were compared with clinical judgements made at the time of recruitment into the study and later by 3 clinicians using the information collected by the lay interviewers. Agreement between the CIE and the clinicians' diagnoses was as great as agreement between the clinicians themselves, meeting or exceeding agreement observed for comparable instruments designed for lay administration. PMID- 8447243 TI - One hundred years of suicide in New Zealand. AB - Suicide rates were obtained for New Zealand from 1889 to 1988. The overall rate for women has been stable since the 1930s, and the male rate showed marked peaks in the early 1930s and in the 1980s. Analysis of rates by age group revealed that the 1930 male peak was due to increases among the middle-aged and elderly men, and the current peak is due to increases among young men. Possible explanations for fluctuations in suicide rates over the last century are discussed. PMID- 8447244 TI - Effect of lithium dosing schedule on urinary output. AB - Lithium has been reported to induce polyuria in up to 35% of patients receiving it. It has been suggested that polyuria may be reduced by using single rather than multiple daily dosing. However, this information is based on non-randomized studies, which used higher serum lithium levels than are currently used. In fact, the incidence of polyuria may be lower at currently used lithium levels, and the benefits of a single daily dose regimen on urine volume at these levels have not been assessed. We conducted a prospective randomized study to test the hypothesis that switching patients from multiple daily dose lithium to single daily dose lithium would significantly lower urine volume. Twenty-four patients previously stabilized on multiple daily dosing were randomly allocated to either single or multiple daily dose lithium. Twenty-four-hour urine volume, serum creatinine, creatinine clearance and serum lithium were measured at study entry and completion. Switching to single daily dose lithium did not significantly reduce the 24-h urine volume. PMID- 8447245 TI - Need-adapted treatment of schizophrenia: a five-year follow-up study from the Turku project. AB - The five-year follow-up results of 28 first-contact schizophrenic patients are compared with an older patient series of 53 patients from the same district. The treatment of the new series followed the principles of the need-adapted model. The emphasis was on immediate initial crisis-oriented family interventions. The treatment of the old series followed psychodynamic principles with an emphasis on individual and milieu therapy. The patients in the new group manage better with half the number of hospital days and less outpatient treatment. The differences are most clear in men. The crisis orientation caused failure in sustaining longer treatment relationships. This was harmful for patients and families with a more chronic development. In future, better continuity of treatment must be emphasized. PMID- 8447246 TI - Music and speech processing in the first year of life. PMID- 8447247 TI - Does reading make you smarter? Literacy and the development of verbal intelligence. AB - The studies reported here represent the first steps in the development of a new research paradigm for studying the unique cognitive correlates of literacy. Reading experience exhibits enough isolable variance within a generally literate society to be reliably linked with cognitive differences. Research on such links is therefore facilitated because the consequences of engaging in literacy activities can be studied without necessarily obtaining totally illiterate samples or setting up cross-cultural comparisons. Issues that are at least analogous issues to those raised in cross-cultural research can be studied within literate societies with a paradigm such as this, and therefore the speed with which we can answer questions about the cognitive consequences of literacy may be greatly increased because more studies can be carried out, larger samples can be studied, and the range of the cognitive domains tapped can be widened. Research in this area appears to have been stifled because of the widespread acceptance of the most extreme interpretations of the outcome of Scribner and Cole's (1981) investigation--interpretations that have slowly diffused throughout the literature without being accompanied by any new data. These conclusions are fueled by a powerful social critique that advances the argument that the positive cultural and economic effects of literacy have been overstated--indeed, that literacy is, if anything, a repressive force (Auerbach, 1992; Street, 1984, 1988; Stuckey, 1991). Educational theorists such as Frank Smith accused the educational establishment of "overselling" literacy and have argued that "Literacy doesn't generate finer feelings or higher values. It doesn't even make anyone smarter" (1989, p. 354). The data reported herein appear to indicate that these theorists could well be wrong in this conclusion. If "smarter" means having a larger vocabulary and more world knowledge in addition to the abstract reasoning skills encompassed within the concept of intelligence, as it does in most laymen's definitions of intelligence (Stanovich, 1989; Sternberg, 1990), then reading may well make people smarter. Certainly our data demonstrate time and again that print exposure is associated with vocabulary, general knowledge, and verbal skills even after controlling for abstract reasoning abilities (as measured by such indicators as the Raven).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8447248 TI - Sex-of-sibling effects: Part I. Gender role, intelligence, achievement, and creativity. PMID- 8447249 TI - The concept of same. PMID- 8447250 TI - Planning as developmental process. PMID- 8447251 TI - Effects of feeding method on infant temperament. PMID- 8447252 TI - The development of reading. PMID- 8447253 TI - Learning to read: a theoretical synthesis. PMID- 8447254 TI - An overview of occupational hazards among veterinarians, with particular reference to pregnant women. AB - Veterinarians are challenged by an imposing group of occupational hazards, including exposure to ionizing radiation, injury, infectious agents, and chemicals. In this paper, the health hazards in the typical veterinary practice are inventoried, and the risks of each are assessed. During the past few decades, there has been a significant increase in women entering the veterinary profession. Information is presented concerning the impact of various occupational hazards on the health of female practitioners and paraprofessionals, particularly in regard to the reproductive system. Many of the occupational hazards are exclusively, or more significantly, detrimental to females (particularly when pregnant) and to their unborn. Women must be aware of and avoid these hazards in their clinical environment. The purpose of this review is to assist practitioners in identifying and assessing the hazards in their practice and determining what steps must be taken to eliminate or reduce them. PMID- 8447255 TI - The effect of hand-held radio operation on audio dosimeters. AB - Six models of audio dosimeters from five manufacturers were tested to determine the effect of radio frequency (r-f) interference caused by the operation of hand held radios near the dosimeters on the measured average sound pressure level in a controlled noise field. Exposures were in a reverberant chamber at levels of 36, 80, and 92 dBA to an octave of noise centered at 1 kHz. Two walkie-talkie type radios, one operating at 160 mHz and the other operating at 460 mHz were used to generate the r-f field. The radios were operated on two duty cycles (2 or 3 cycles/min) during the recording period. Reported measures, such as average sound pressure level and peak sound pressure level, were compared for each noise exposure condition with and without operation of the hand-held radio. The results indicate that all makes and models of the dosimeters that were tested gave false readings under some conditions. These values always exceeded the reading in the noise alone control condition and varied by as much as 45 dB above the "true" level. Because each dosimeter behaved differently--including different samples of identical models--it was not Rather, steps are recommended to help users identify potential r-f contamination on dosimeter performance in the field. PMID- 8447256 TI - Effects of shape, size, and air velocity on entry loss factors of suction hoods. AB - This study further elucidated the effects of air velocity, aspect ratio (face length to face width), and area ratio (face area to duct area) on entry loss factors of suction hoods. A full scale ventilation system was utilized to determine the entry loss factor attributable to each of 20 square and rectangular hoods with a 90 degrees included angle. Static and velocity pressures were measured using Pitot tubes connected by tubing to piezo-resistive pressure transducers and inclined tube manometers. The entry loss factor, Fh, is the ratio of hood total pressure loss to mean velocity pressure. Values of Fh determined in this study ranged from 0.17-1.85. The values of Fh were a hyperbolic function of area ratio with a region rapidly increasing change for area ratios less than 5. For area ratios greater than 5, the values of Fh approached an asymptote of 0.17. Among hoods with a given area ratio (e.g., 2.5, 5.1, or 10.2), values of Fh were independent of aspect ratio. To a limited extent, Fh values decreased as mean air velocities increased from 319-1770 m/min (1046-5807 feet/min). PMID- 8447257 TI - Prevalence of hyperapobetalipoproteinemia and other lipoprotein phenotypes in men (aged < or = 50 years) and women (< or = 60 years) with coronary artery disease. AB - The prevalence and clinical characteristics of hyperapobetalipoproteinemia (hyperapoB) and other phenotypes of dyslipoproteinemia were examined in 99 men (aged < or = 50 years) and 104 women (< or = 60 years) undergoing elective diagnostic coronary arteriography. HyperapoB was the most common phenotype (34%) associated with premature coronary artery disease (CAD). Only 20.2% of patients with CAD had a normal lipoprotein phenotype. The significant odds ratios for CAD were as follows: hypertriglyceridemic hyperapoB 17.45 (p < 0.0001), type IV 6.54 (p = 0.0001), type IIa 4.73 (p = 0.008), normotriglyceridemic hyperapoB 2.54 (p = 0.03) and type IIb 8.73 (p = 0.05). The strong association of hypertriglyceridemic hyperapoB with CAD reflected the multiplicative effect of increased low-density lipoprotein apolipoprotein B and endogenous hypertriglyceridemia, and was independent of the effects of age, sex, diabetes mellitus, systemic hypertension, body mass index and cigarette smoking. The ratio of apolipoprotein B to A-1 was better than those of low-density to high-density lipoprotein cholesterol and total to high-density lipoprotein cholesterol at discriminating dyslipidemic phenotypes from normal. Obesity was increased approximately 1.5 to two-fold in the hypertriglyceridemic phenotypes, diabetes was more prevalent in hypertriglyceridemic hyperapoB (6.8-fold; p < 0.001) and type IV (4.4-fold; p = 0.02), and hypertension was increased 1.5- to twofold in most dyslipidemic groups. The data indicate that hyperapoB and endogenous hypertriglyceridemia both contribute to the risk of premature CAD. PMID- 8447258 TI - Neutralizing antibodies to streptokinase four years after intravenous thrombolytic therapy. AB - Neutralization antibodies to streptokinase increase to high levels within several days of administration. It is not known how long these high levels persist. The time course of antibody levels needs to be further characterized owing to the increasing need to readminister thrombolytic therapy, and to the possibility that these antibodies may compromise the safety and efficacy of a further dose of streptokinase or streptokinase-containing compounds. In this study, paired streptokinase neutralization titers (in vitro functional assay) and specific antistreptokinase immunoglobulin G (IgG) antibody levels were measured in 145 patients who received streptokinase between 10 and 48 months previously. Serologic evidence of recent streptococcal infection was also sought. Neutralization titers sufficient to inactivate a conventional dose of 1,500,000 units of streptokinase were still present in 50% of patients (95% confidence interval 36-64) at 24 months, 48% (34-62) at 36 months, and 51% (37-71) at 48 months after streptokinase administration. Levels of specific antistreptokinase IgG antibodies also remained constant over the 1- to 4-year period. Neutralization titers were weakly correlated with specific IgG levels (r = 0.35). Antistreptolysin titers > or = 250 and > or = 333 IU/ml were present in 30% (24 38) and 12% (8-18) of these patients, respectively. Neutralization titers were not correlated with antistreptolysin titers. Neutralizing antibodies (assessed by an in vitro functional assay) remained high in 51% of patients 4 years after intravenous streptokinase administration. It is not known whether persisting high in vitro neutralization titers affect the efficacy and safety of repeat administration of streptokinase or streptokinase-containing compounds. PMID- 8447259 TI - Prognostic usefulness of positive or negative exercise stress echocardiography for predicting coronary events in ensuing twelve months. AB - Stress echocardiography is useful in diagnosing myocardial ischemia in patients with significant coronary artery disease. This study examines the correlation between the results of exercise stress echocardiography and cardiac event rates within 12 months after testing in patients referred for evaluation of possible myocardial ischemia. Cardiac events, defined as myocardial infarction, coronary artery bypass surgery, percutaneous transluminal coronary angioplasty or death, were tabulated for 360 patients with > or = 12 months of follow-up, or a cardiac event within 12 months of follow-up, or both. Wall motion abnormalities at rest were present in 60% of patients. A positive stress echocardiogram, defined as the development of new or worsened wall motion abnormalities, was obtained in 18% of patients (65 of 360), and > or = 1 cardiac event during follow-up was present in 14% (n = 49). A cardiac event occurred in 34% of patients (22 of 65) with a positive stress echocardiogram and in 9% (27 of 295) with a negative one. Myocardial infarctions occurred in 9% of patients with a positive stress echocardiogram compared with 2% with a negative test. An insufficient exercise capacity to reliably exclude ischemia was present in 63% of patients (17 of 27) with a cardiac event despite a negative stress echocardiogram. The predictive value of the stress echocardiographic results was enhanced by combining these results with the electrocardiographic results. In summary, a positive stress echocardiogram was associated with a threefold increased incidence of any cardiac event, and a fourfold increased incidence of myocardial infarction within 12 months of follow-up compared with a negative stress echocardiogram.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447260 TI - Frequency and consequences of intimal hyperplasia in specimens retrieved by directional atherectomy of native primary coronary artery stenoses and subsequent restenoses. AB - Although intimal hyperplasia is a frequent occurrence after arterial interventional procedures, the overall frequency and significance of intimal hyperplasia in primary coronary lesions has not been previously addressed. The incidence of intimal hyperplasia was therefore examined using standard light microscopy in specimens obtained from native coronary arteries of patients undergoing directional coronary atherectomy. The associated clinical history, angiographic results and clinical outcomes were also tabulated. Intimal hyperplasia was identified in 51 of 55 patients (93%) treated with directional coronary atherectomy for restenosis after a prior intervention. These restenosis lesions had less acute gain in lumen diameter after directional coronary atherectomy, a smaller late lumen diameter, more severe late stenosis (p < 0.04), and tended to have more restenosis defined as late stenosis > or = 50% (restenosis rate 40% for prior restenosis vs 26% for primary lesions). Surprisingly, however, intimal hyperplasia was also identified in 45 of 102 (44%) primary stenoses. Primary lesions (n = 45) with intimal hyperplasia were more likely to occur in younger patients and in the left anterior descending artery than were either primary lesions without intimal hyperplasia (n = 57) or prior restenosis lesions. There were otherwise no differences in the baseline characteristics, angiographic findings or clinical outcome of primary lesions with or without intimal hyperplasia (restenosis rate 28 and 24%, respectively). The event-free survival (72% at 12 months) was similar in all 3 groups. Thus, even though intimal hyperplasia is an almost universal finding in restenosis lesions, intimal hyperplasia is not specific for restenosis since histologically identical hyperplasia may be found in nearly half of primary coronary artery stenoses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447261 TI - Influence of elastic recoil on restenosis after successful coronary angioplasty in unstable angina pectoris. AB - The elastic behavior of the dilated coronary vessel has been reported to affect the immediate results of coronary angioplasty. To determine whether elastic recoil may also influence the long-term restenosis process, 98 consecutive patients with unstable angina and 1-vessel disease were studied. An automated coronary quantitative program was used for the assessment of balloon and coronary luminal diameters. Elastic recoil was defined as the percent reduction between minimal balloon diameter at the highest inflation pressure and minimal lesion diameter immediately after coronary angioplasty. Follow-up coronary arteriography was performed 8 to 12 months after the procedure in all patients. The mean elastic recoil averaged 17.7 +/- 16% and was correlated to the degree of residual stenosis immediately after coronary angioplasty (r = 0.64; p < 0.001). Restenosis, defined as > 50% diameter stenosis at follow-up, developed in 53 patients (54%). There was no correlation between the degree of elastic recoil and the changes in minimal lesion diameter observed during follow-up, whereas a positive correlation between the amount of elastic recoil and the incidence of restenosis was documented (r = 0.84; p < 0.05). Thus, the elastic properties of the dilated vessel do not influence the active process of restenosis. However, because elastic recoil negatively influences the initial results of angioplasty, it is more likely that further reductions in lumen diameter during follow-up can reach a threshold of obstruction considered critical for a binary definition of restenosis. PMID- 8447262 TI - In vivo validation of compensatory enlargement of atherosclerotic coronary arteries. AB - Necropsy examinations and epicardial ultrasound studies have suggested that atherosclerotic coronary arteries undergo compensatory enlargement. This increase in vessel size may be an important mechanism for maintaining myocardial blood flow. It also is of fundamental importance in the angiographic study of coronary disease progression and regression. The purpose of this study was to determine, using intracoronary ultrasound, whether coronary arteries undergo adaptive expansion in vivo. Forty-four consecutive patients were studied (30 men, 14 women; mean age 56 +/- 10 years). Eighty intravascular ultrasound images were analyzed (32 left main, 23 left anterior descending and 25 right coronary arteries). Internal elastic lamina area, a measure of overall vessel size increased as plaque area expanded (r = 0.57, p = 0.0001, SEE = 5.5 mm2). When the left main, left anterior descending and right coronary arteries were examined individually, there continued to be as great or greater positive correlation between internal elastic lamina and plaque area (left anterior descending: r = 0.75, p = 0.0001; right coronary arteries: r = 0.63, p = 0.0007; left main: r = 0.56, p = 0.0009), implying that each of the vessels and all in aggregate underwent adaptive enlargement. When only those vessels with < 30% area stenosis were examined, internal elastic lamina correlated well with plaque area (r = 0.79, and p = 0.0001), and for each 1 mm2 increase in plaque area, internal elastic lamina increased 2.7 mm2. This suggests that arterial enlargement may overcompensate for early atherosclerotic lesions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447263 TI - Long-term follow-up of patients initially diagnosed with syndrome X. AB - The clinical course of 30 patients (27 women and 3 men) diagnosed with syndrome X (angina pectoris, positive exercise test and normal coronary arteries) was evaluated during 5-year follow up. Patients were divided at the control examination into 2 groups according to the median value of the heart rate/blood pressure product variation from rest to the first stage of a modified Bruce protocol, as follows: group 1 < or = 1,050 (n = 15) and group 2 > 1,050 mm Hg x beats/min (n = 15). All patients were followed at 6-month intervals during a mean follow-up of 60 +/- 8 months. During follow-up, chest pain was unchanged in 20 patients, decreased in severity and frequency in 9 (7 in group 1, and 2 in group 2), and disappeared in 1 in group 2; 3 patients in group 1 had prolonged episodes of anginal chest pain (> 30 minutes) that needed hospitalization. In group 2, 7 patients developed systemic hypertension, 4 had a progression of exercise-induced left bundle branch block to constant left bundle branch block, and 4 continued to develop rate-dependent block during exercise, but at a reduced heart rate. In the latter 8 patients, left ventricular ejection fraction at rest during follow-up decreased significantly from 61 +/- 6% to 51 +/- 8% (p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447264 TI - Usefulness of thallium-201 for distinction of ischemic from idiopathic dilated cardiomyopathy. AB - Thallium-201 scintigraphic defects are observed in most patients with ischemic cardiomyopathy and also can be found in idiopathic dilated cardiomyopathy. To determine the ability of qualitative and quantitative perfusion parameters to differentiate these entities, thallium-201 exercise testing was performed in 51 patients with coronary arteriography referred for evaluation of severe congestive heart failure. All patients had a left ventricular ejection fraction < 35%. Thirty-one ischemic patients had coronary stenosis > 70% in > or = 1 artery, and 20 idiopathic patients had no coronary stenosis or identifiable cause of heart disease. Similar exercise capacity, ejection fraction and sex distribution were found in both groups. Ischemic patients more often had severe perfusion defects (97 vs 25%; p = 0.00001), large perfusion defects involving > or = 40% of the left ventricular contour (100 vs 80%; p = 0.01), and increased thallium-201 lung uptake (94 vs 65%, p = 0.01). Large severe defects were present in 90% of ischemic and only 5% of idiopathic patients. On quantitative analysis, the area of the thallium-201 curve less than normal was greater in ischemic than idiopathic patients (14.8 +/- 9.5% vs 3.3 +/- 2.8%; p = 0.001). The degree and severity of redistribution were similar in both groups. Multivariate analysis identified the qualitative parameters of increased thallium-201 lung uptake, severe defects and large severe defects as the only independent predictors of the presence of ischemic disease. The presence of large severe defects had a 97% predictive value for ischemic cardiomyopathy. The absence of severe defects had a 94% predictive value for idiopathic dilated cardiomyopathy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447265 TI - Scintigraphic monitoring of coronary artery occlusion due to Kawasaki disease. AB - Noninvasive monitoring of the process of coronary occlusion will probably aid in determining the timing of therapeutic interventions for Kawasaki disease. A pair study of coronary angiography and thallium scintigraphy after dipyridamole infusion-single-photon emission computed tomography with dipyridamole infusion (Dp-SPECT) was repeated at least twice at intervals of several years in 29 patients, and these findings were compared and analyzed in a chronologic manner. The current study demonstrated that angiographic stenosis was more severe, with an increase in the severity of the perfusion defect. Positive rates determined by Dp-SPECT increased with increasing severity of stenosis on angiography. Angiographic findings from the first to the second serial study that showed worsening, no change and improvement were correctly diagnosed from scintigraphic changes in 94% of coronary arterial lesions. About half of the arteries with progression in stenotic severity could be found before complete occlusion by scintigraphic monitoring. It is concluded that Dp-SPECT can be used as a noninvasive monitor of the occurrence and progression of coronary stenoses due to Kawasaki disease. PMID- 8447266 TI - Antiarrhythmic and pharmacokinetic evaluation of intravenous recainam in patients with frequent ventricular premature complexes and unsustained ventricular tachycardia. AB - The pharmacokinetics, antiarrhythmic activity and safety of intravenously administered recainam were evaluated in 15 men and 3 women. All patients had frequent (> 30/hour) ventricular premature complexes (VPCs) and unsustained ventricular tachycardia. Recainam was administered at a loading dose of 4.5 mg/kg/hour over 40 minutes, followed by a maintenance infusion of 0.9 mg/kg/hour for 23 hours and 20 minutes. Sixteen patients had satisfactory efficacy data. The mean frequency of total VPCs decreased by 92.6% and the mean frequency of runs decreased by 99.9% during the maintenance infusion. Suppressions of > or = 70% of total VPCs and > or = 90% of runs were maintained over the 23-hour, 20-minute maintenance infusion period in 16 of the 18 patients. During the maintenance infusion, hourly group plasma recainam concentrations ranged from mean +/- SD 2.6 +/- 0.7 to 3.4 +/- 0.9 micrograms/ml. Patients were observed for 24 hours after termination of the infusion. Periodic blood samples were obtained during and after termination of the infusion to determine recainam concentration. Urine specimens were collected over scheduled intervals to determine urinary excretion of recainam. A 2-compartment pharmacokinetic model was used to analyze the data. The following pharmacokinetic parameters were obtained: terminal elimination half life, 5.0 +/- 0.8 hours; systemic clearance, 0.27 +/- 0.08 liter/hour/kg; and central and steady-state volume of distribution, 0.32 +/- 0.11 and 1.4 +/- 0.4 liter/kg, respectively. Adverse experiences were reported in 4 of the 18 patients, possibly drug-related in 2; none was considered severe or required discontinuation of recainam.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447267 TI - Endocardial mapping during sinus rhythm in patients with coronary artery disease and nonsustained ventricular tachycardia. AB - Programmed stimulation in patients with nonsustained ventricular tachycardia (VT) and coronary artery disease (CAD) induces sustained VT in 30 to 50% of patients. The presence of inducible, sustained VT identifies patients at high risk for sudden death. This study sought to determine whether patients with nonsustained VT who have inducible, sustained VT would have differences of left ventricular endocardial activation and conduction compared with those of patients without inducible, sustained VT. Thirty-six patients with CAD referred for evaluation of nonsustained VT underwent programmed ventricular stimulation and catheter mapping of left ventricular endocardial activation. Using previously validated methods, electrograms were classified as normal, abnormal or fractionated based on measurement of local electrogram duration and amplitude. Programmed stimulation induced sustained, uniform VT in 16 of 36 patients (44%). Patients with inducible, sustained, uniform VT had significantly more sites with abnormal (48%) and fractionated (5.5%) electrograms than did those without inducible VT (35% abnormal and 0.4% fractionated; p = 0.05 and 0.01, respectively). Patients with inducible VT had a mean of 15% of mapped sites displaying late electrograms versus only 3% in those without inducible VT (p < 0.01). The duration of the longest local electrogram in patients with inducible, sustained, uniform VT was 128 ms compared with 100 ms in those without inducible VT (p < 0.001). Thus, patients with CAD presenting with nonsustained VT who have inducible, sustained, uniform VT have significantly greater degrees of local conduction slowing and delayed activation than do those without inducible, sustained, uniform VT. These observations support reentry as the mechanism of the induced arrhythmias in these patients. PMID- 8447268 TI - Factors for transient entrainment of ventricular tachycardias by rapid atrial pacing. AB - Thirteen patients with sustained ventricular tachycardia (VT) were studied to elucidate predisposing factors for the development of constant and progressive fusion by rapid atrial pacing. All patients demonstrated transient entrainment by rapid ventricular pacing during VT. Constant and progressive fusion were observed in 7 patients (positive group) during rapid atrial pacing, but not in 6 (negative group). In the positive group, VT was induced by atrial pacing in 2 patients. The demonstration of constant and progressive fusion by atrial pacing was not dependent on QRS morphology or ventriculoatrial conduction during VT. VT cycle length in the positive group (363 +/- 59 ms) was longer than in the negative group (297 +/- 31 ms; p = 0.033). The maximal atrial pacing rate producing 1:1 atrioventricular (AV) conduction in the positive group was 171 +/- 18 beats/min compared with 125 +/- 22 beats/min in the negative group (p = 0.002). There were distinct differences between the positive and negative groups in the ratio of VT cycle length to minimal atrial cycle length causing 1:1 AV conduction (1.02 +/- 0.12 vs 0.61 +/- 0.12; p = 0.0001). It is concluded that AV conduction, VT cycle length and especially their ratio are important factors for the development of transient entrainment by rapid atrial pacing during VT. Therefore, atrial pacing can be used as an easy and useful method to examine transient entrainment during VT. PMID- 8447269 TI - Radiofrequency ablation of the inferior vena cava-tricuspid valve isthmus in common atrial flutter. AB - Endocardial mapping has suggested that common atrial flutter (AF) is based on right atrial reentry surrounding the inferior vena cava (IVC). The isthmus between the IVC and the tricuspid valve (TV) appears essential to close the circuit. To test this hypothesis, radiofrequency was applied to the IVC-TV isthmus, with catheter electrodes, in 9 patients with AF. Mapping confirmed a right atrial circuit surrounding the IVC in all. In 4 patients another type of AF was induced that followed the circuit in the opposite direction. Radiofrequency interrupted AF in all patients. Multiple endocardial recordings showed that interruption was due to activation block at the point of application. Radiofrequency produced very brief or sustained, atrial fibrillation in 2 patients, which resulted in sinus rhythm. AF recurred in 4 patients with the same activation pattern and was interrupted again with radiofrequency in the IVC-TV isthmus in 3. AF was noninducible in 7 patients after 1 to 4 sessions. AF-free periods of 2 to 18 months without drugs were observed after radiofrequency, but 2 patients had paroxysmal atrial fibrillation. These results confirm that the IVC TV isthmus is an essential part of the AF circuit. Ablation of this area may be of therapeutic value, but technical improvements are needed. Long-term efficacy of the procedure is uncertain. PMID- 8447270 TI - Recurrence of paroxysmal atrial fibrillation or flutter after successful cardioversion in patients with normal left ventricular function. AB - One hundred twenty-four consecutive patients (85%) with paroxysmal atrial fibrillation (AF) and 21 (15%) with atrial flutter (AFI) were studied immediately after pharmacologic or electrical cardioversion to sinus rhythm. Mean age was 59 +/- 13 years (range 23 to 79). Patients with reduced left ventricular function were excluded from the study. After restoration to sinus rhythm, the clinical course of all patients was followed for the first recurrence of paroxysmal AF or AFI irrespective of the therapeutic approach. Mean follow-up was 23 +/- 16 months. After 12 months of follow-up, 50% of all patients remained in sinus rhythm. Univariate analysis indicated that coronary artery disease (relative risk 1.9; 95% confidence interval 0.9-3.9), history of paroxysmal AF or AFI (2.3; 1.1 5.0), female sex (2.3; 1.1-4.6), pulmonary disease (3.9; 1.9-7.6) and valvular heart disease (4.4; 2.2-8.8) were associated with an increased risk for recurrent or frequent episodes of paroxysmal AF or AFI. No predictors were found to be associated with a decrease in length of the recurrence-free period after successful conversion to sinus rhythm. Multivariate analysis identified history of AF or AFI (odds ratio 2.5; 95% confidence interval 0.9-6.4), coronary artery disease (3.1; 1.1-8.2) and female sex (3.4; 1.3-8.9) as independent predictors for recurrent or frequent episodes of paroxysmal AF or AFI. The presence of these risk factors should be taken into account when prophylactic therapy with antiarrhythmic drugs is being considered in the treatment of paroxysmal AF or AFI. PMID- 8447271 TI - Late follow-up of dual-chamber rate-adaptive pacing. AB - Dual-chamber pacing systems with sensor-based rate-adaptive capability (DDDR pacemakers) provide paced patients with the potential benefits of both a reliable chronotropic response and maintenance of atrioventricular (AV) synchrony. However, there is concern that clinical and programming complexities may necessitate frequent reprogramming of pacemakers from the DDDR mode to less physiologic pacing modes (in particular VVI or VVIR). Consequently, this study assessed the stability of pacing-mode programming, and the factors affecting pacing-mode selection in patients with a DDDR-capable pacing system. Clinical status during follow-up (18.2 +/- 6.7 months) was assessed in 75 patients. Principal diagnoses providing an indication for pacing were: (1) AV block alone, 18 of 75 patients (24%); (2) sick sinus syndrome alone, 41 (55%); and (3) combined AV block and sick sinus syndrome, 16 (21%). Twenty-three patients had history of atrial tachyarrhythmias. At implantation, 66 devices (88%) were programmed to DDDR mode, 7 (9%) to DDD, and 2 (3%) to DVIR. At last follow-up, the respective distribution of programmed modes was 83% DDDR, 10% DDD, 4% DVIR and 3% VVIR. During the study, the initial pacing mode remained unchanged in 54 patients (72%) and needed modification in 21 (28%). Of the latter 21 patients, atrial tachycardia was the basis for a programming change in 11 (52%), of whom 8 had history of atrial tachycardias. In general, postimplant atrial arrhythmia occurrences proved controllable, and ultimately return to a rate-adaptive dual chamber pacing mode (DDDR, DDD or DVIR) was achieved in most cases. The remaining reprogrammings were primarily to optimize hemodynamic benefit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447272 TI - First- or second-degree atrioventricular block as a risk factor in idiopathic dilated cardiomyopathy. AB - To evaluate the significance of clinical, hemodynamic and electrocardiographic risk factors in idiopathic dilated cardiomyopathy 94 patients were followed prospectively for 49 +/- 37 months. During follow-up, 30 patients died, 13 died suddenly, 13 died of congestive heart failure and 4 of other causes. Follow-up was completed in 85 patients, and overall cardiac mortality was 31%. Univariate analysis revealed left ventricular ejection fraction among 20 variables as the major indicator of risk of both cardiac death of all causes and sudden cardiac death separately. Multivariate overall analysis determined 3 independent risk factors in the following order for all causes of cardiac death: Ventricular pairs > 40/24 hours (RR 7.2, p < 0.0001), left ventricular ejection fraction < or = 35% (RR 6.5, p < 0.001) and first- or second-degree atrioventricular (AV) block (RR 3.1, p < 0.05). In the subset of patients with ejection fraction < or = 35% ventricular pairs > 40 per 24 hours (RR 10.7, p < 0.001), AV block (RR 3.9, p < 0.05), and the missing administration of vasodilators (RR 3.3, p < 0.05) were the most important. The chief risk factors for sudden cardiac death were age (RR 7.4, p < 0.01) and AV block (RR 4.6, p < 0.05) by adjustment for age, and ejection fraction < or = 35% (RR 7.1, p < 0.01) and AV block (RR 4.2, p < 0.05) if not adjusted for age. A differentiation into 4 risk groups was attempted. The additional independent prognostic importance of AV block was shown, especially in combination with reduced ejection fraction or a high incidence of ventricular pairs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447273 TI - Semiquantitative assessment of mitral regurgitation by Doppler color flow imaging in patients aged < 20 years. AB - Doppler color flow imaging is a rapid, noninvasive method to estimate the severity of mitral regurgitation (MR) in adult patients; theoretically, it should be possible to use the technique at least as successfully in infants and children, because problems with beam penetration should be diminished. Doppler color flow studies in 27 pediatric patients (age range 12 days to 17 years, median 7 months) with various degrees of MR (but without coexistent aortic regurgitation or intracardiac shunt) were analyzed. All patients underwent left ventriculography within 2 weeks of their color Doppler examination. Three sets of parameters were investigated, including: (1) maximal length of regurgitant jet: by itself, and indexed to cube root of body surface area (BSA) and to left atrial depth; (2) proximal width of jet; by itself, and indexed to cube root of BSA and to diameter of mitral annulus; and (3) regurgitant jet area (RJA): by itself, and indexed to BSA and left atrial area (LAA). Of these parameters, RJA indexed to BSA, and the ratio of RJA/LAA had the best correlation with angiographic grading (r = 0.84 and 0.92, respectively). With our instrumentation, the "cutoff" values in infants and children separating mild, moderate and severe MR appear to be 4 and 10 cm2/m2 for RJA/BSA, and 30 and 50% for RJA/LAA, respectively. Both inter- and intraobserver correlations were good for RJA (r = 0.95 and 0.94, respectively), and the ratio of RJA/LAA (r = 0.92 and 0.94, respectively). Semiquantitative assessment of MR appears to be possible in pediatric patients, using 1 instrument and a standardized technique. PMID- 8447274 TI - Factors influencing left ventricular systolic function in nonhypertensive morbidly obese patients, and effect of weight loss induced by gastroplasty. AB - Heart rate and blood pressure were measured, and echocardiography was performed in 39 patients whose actual body weight was greater than twice their ideal body weight to identify factors influencing left ventricular (LV) systolic function in morbidly obese patients and assess the effect of weight loss on LV systolic function. Patients were studied before and after weight loss induced by gastroplasty. The study cohort was 133 +/- 8% overweight before weight loss and 39 +/- 7% overweight at the nadir of weight loss. Before weight loss, LV fractional shortening varied inversely with LV internal dimension in diastole (an indirect index of preload), LV end-systolic wall stress and systolic blood pressure (indexes of afterload). The weight loss-induced change in LV fractional shortening varied directly with the pre-weight loss LV internal dimension in diastole, LV end-systolic wall stress and systolic blood pressure, and inversely with the pre-weight loss LV fractional shortening. The weight loss-induced change in LV fractional shortening varied inversely with the weight loss-induced changes in LV end-systolic stress and systolic blood pressure. In patients with reduced LV fractional shortening (n = 14), weight loss produced a significant increase in LV fractional shortening that was accompanied by a significant decrease in LV internal dimension in diastole, LV end-systolic stress and systolic blood pressure. The results suggest that LV loading conditions have an important role in determining LV systolic function in morbidly obese patients. Improvement in LV systolic function in these patients is closely related to weight loss-induced alterations in LV loading conditions. PMID- 8447275 TI - Detection and assessment by positron emission tomography of a genetically determined defect in myocardial fatty acid utilization (long-chain acyl-CoA dehydrogenase deficiency). AB - Genetic defects in fatty acid oxidation are important, inherited causes of cardiomyopathy, skeletal myopathies, and childhood sudden death. The clinical manifestations and their severity vary widely among affected subjects and different age groups. Although measurement of serum and urinary fatty acid intermediary metabolites and enzymatic assays establish the diagnosis of a defect in fatty acid oxidation, they do not predict the specific clinical manifestations nor their severity in a given subject. To determine whether impaired myocardial fatty acid utilization, indicative of cardiac phenotypic expression of a specific genetic abnormality in fatty acid oxidation, can be detected, cardiac positron emission tomography with the metabolic tracers carbon-11-labeled palmitate and acetate was performed in 6 patients with long-chain acyl-CoA dehydrogenase (ACD) deficiency and in 9 control subjects. The myocardial extraction of both tracers was similar in patients and controls. The rate of clearance of palmitate from myocardium was significantly prolonged in patients compared with that in control subjects (0.022 +/- 0.012 vs 0.061 +/- 0.033 min-1; p < 0.025), indicative of a decreased rate of oxidation of long-chain fatty acids. Furthermore, the extent of diminution of clearance of palmitate, quantified in terms of the rate of clearance for palmitate divided by that for acetate (to correct for individual differences in overall mitochondrial oxidative metabolic flux), correlated with the clinical severity of the long-chain ACD deficiency. Accordingly, noninvasive evaluation with positron emission tomography may not only facilitate diagnosis, but also enable assessment of the pathogenetic impact and effects of therapeutic interventions in the hearts of subjects with specific, inherited defects in fatty acid oxidative metabolism. PMID- 8447276 TI - Polymorphous ventricular tachycardia early after acute myocardial infarction. PMID- 8447277 TI - Use of claims data for determining the appropriateness of ambulatory cardiac monitoring. PMID- 8447278 TI - Effect of left and right lateral decubitus positions on mitral flow pattern by Doppler echocardiography in congestive heart failure. PMID- 8447279 TI - Direct in vivo evaluation of pulmonary arterial pathology in chronic congestive heart failure with catheter-based intravascular ultrasound imaging. PMID- 8447280 TI - Evidence for a prognostic role of the JT interval. PMID- 8447281 TI - Antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease. PMID- 8447282 TI - Breast disease in the 1990s. Patchwork quilt and growth industry. PMID- 8447283 TI - Serum transferrin receptor level is not altered in invasive adenocarcinoma of the breast. AB - The transferrin receptor is expressed on the surface of rapidly dividing cells that require iron as a co-factor for essential redox reactions and deoxyribonucleotide synthesis. Transferrin receptors are expressed on the surface of breast carcinoma cells but not on benign breast tumor cells. In this study, the authors investigated whether transferrin receptor concentrations in the serum were elevated in patients with invasive adenocarcinoma of the breast. The transferrin receptor was isolated and purified from human placenta by affinity chromatography. The serum transferrin receptor concentration was determined using an enzyme-linked immunosorbent assay in 19 patients with invasive breast adenocarcinoma, 12 of whom had involvement of axillary lymph nodes. These results were compared with those from 16 normal age-matched female controls. In the invasive breast cancer group, the range of transferrin receptor concentrations was 2.60-7.34 mg/L (mean, 4.44 mg/L) compared with 2.85-8.80 mg/L (mean, 5.49 mg/L) in the control group. Nine patients with in situ adenocarcinoma of the breast had transferrin receptor concentrations of 3.68-6.66 mg/L (mean, 4.94 mg/L). For both the invasive carcinoma group and the in situ group, the means were not significantly different from those of the control group (P = 0.06 and 0.32, respectively). It was concluded that the differential expression of transferrin receptor on the surface of malignant tumor cells in adenocarcinoma of the breast was not reflected by changes in circulating transferrin receptor concentrations. PMID- 8447284 TI - Multicentricity in breast cancer. A study of 366 cases. AB - A total of 366 consecutive modified radical mastectomy specimens were studied for determination of multicentricity. The authors found that 187 samples (49.1%) were multicentric. Ten specimens contained in situ carcinoma without an infiltrating component; eight of them were multicentric. Multicentricity was correlated with various laboratory and clinical features, including patient age, tumor size, histologic type of breast cancer, tumor grade, presence and values of estrogen and progesterone receptors, the amount of solid tissue in the breast, and the family history. The data were organized in eight independent dimensions, four ordinal and four cardinal. Correlation analysis was applied to a cross tabulation supplemented with other statistical tests. The authors found that the factors related to multicentricity were the age of the patient, the size and the histologic type of the tumor, levels of the progesterone receptors more than 50 fmol/mg of protein, and the amount of solid tissue in the breasts. Tumor grade, estrogen receptors levels, and family history were not related to multicentricity. It was concluded that multicentricity is a frequent property of breast cancer. It is more common in young and perimenopausal women. Multicentricity occurs in small tumors but is, more common in larger ones. PMID- 8447285 TI - Granulomatous inflammation in bladder wash specimens after intravesical bacillus Calmette-Guerin therapy for transitional cell carcinoma of the bladder. AB - The authors retrospectively reviewed a series of bladder wash cytologic specimens and concurrently available bladder biopsy samples to evaluate granulomatous inflammation in patients receiving intravesical bacillus Calmette-Guerin (BCG) immunotherapy for transitional cell carcinoma of the bladder. Comparisons were made during the 2-month period following six weekly BCG instillations in 25 patients and during the 1-year period following the last dose of BCG in 23 patients. At some point during the 2-month follow-up period, cytologic specimens contained free histiocytes in 64%, histiocyte aggregates (resembling fragments of granulomas) in 76%, and multinucleated histiocytic giant cells in 56% of patients. Similarly, concurrent biopsy samples contained granulomas in 78% and multinucleated giant cells in 56% of patients. During the 1-year period following the last dose of BCG, inflammatory changes peaked within the first 3 months and gradually resolved at 9-12 months. In none of these instances were the cytologic features of granulomatous inflammation misinterpreted as malignant. It was concluded that the cytologic findings after intravesical BCG are more specific than previously realized and closely parallel the histologic changes seen in corresponding bladder biopsy specimens. PMID- 8447286 TI - Experimental study of the cause of myospherulosis. AB - To elucidate the nature of myospherulosis, the authors tried to produce this state in vitro by mixing vitamin E, oleic acid, linoleic acid, and lanolin with human blood components, such as whole blood, washed erythrocytes, plasma, and fixed erythrocytes, respectively. Myospherulosis was produced in all mixtures in these experiments. The authors concluded the following. A thin parent body wall of myospherulosis is formed initially as a result of the physical emulsion phenomenon between lipid-containing materials and blood. Erythrocytes then are enclosed in the parent body. The parent body membrane gradually is reinforced by the deposition of plasma proteins, which are insoluble in ethanol. Thereafter, the erythrocytes become endobodies by the deposition of their contents to the membrane of the parent body. The pores of the endobodies are formed in the process of erythrocyte degeneration. The contents of the erythrocytes, such as hemoglobin, would attach to the parent body. Thus myospherulosis would become complete. In humans, the characteristics of the parent body membranes differ from each other, depending on how much the hemoglobin or a part of the endobody membrane attaches to the parent body membrane. PMID- 8447287 TI - Localized pleural microdeposition of type A amyloid in a patient with rheumatoid pleuritis. Histologic distinction from pleural involvement in systemic amyloidosis. AB - Decorticated pleural tissue from a 74-year-old man with rheumatoid arthritis, an exudative pleural effusion, and normal left ventricular function contained microscopic deposits of amyloid A protein, localized to the interface between a deep layer of dense fibrocollagen and a layer of granulation tissue beneath a surface fibrin exudate. Previously reported instances of pleural amyloid deposition have occurred in patients with presumed systemic amyloidosis, and most such effusions are the result of congestive heart failure. This patient had no evidence of systemic amyloidosis, and this case appeared to be an example of an unusual form of localized amyloidosis, so-called periinflammatory amyloidosis A. These observations suggest that amyloid in a pleural biopsy should not be construed per se to be diagnostic of systemic amyloidosis. PMID- 8447288 TI - Posttransplantation lymphoproliferative disorders. PMID- 8447289 TI - Antineutrophil cytoplasmic antibody in inflammatory bowel and hepatobiliary diseases. High prevalence in ulcerative colitis, primary sclerosing cholangitis, and autoimmune hepatitis. AB - The prevalence of antineutrophil cytoplasmic antibodies was evaluated in patients with ulcerative colitis, primary sclerosing cholangitis, and various other gastrointestinal and hepatobiliary diseases to define the sensitivity and specificity of the test. The presence of antineutrophil cytoplasmic antibodies was detected in alcohol-fixed cytospin preparations of peripheral blood neutrophils with an indirect immunofluorescence technique. A perinuclear staining pattern was considered positive. Thirty-six of 50 patients (72%) with ulcerative colitis and/or primary sclerosing cholangitis had positive results. Twenty-two of 210 patients (10%) in the control group had positive findings, including a significant proportion of patients with autoimmune hepatitis (50%) and non-A, non B and non-C hepatitis (27%). This test for antineutrophil cytoplasmic antibodies has a sensitivity of 72% and specificity of 90% for either ulcerative colitis or primary sclerosing cholangitis. It may be useful in the differential diagnosis of Crohn's disease and ulcerative colitis and in the early diagnosis of ulcerative colitis. It also may be employed to distinguish primary biliary cirrhosis from primary sclerosing cholangitis. PMID- 8447290 TI - Evaluation of the DCL Syphilis-G enzyme immunoassay test kit for the serologic diagnosis of syphilis. AB - Sera have been submitted to the authors' laboratory for syphilis testing at a dramatically increased rate since the start of the human immunodeficiency virus type 1 epidemic. Thus they were interested in evaluating a new enzyme immunoassay, the DCL Syphilis-G test kit (DCL-G, Diagnostic Chemicals Ltd., Oxford, CT) for detection of immunoglobulin G antibodies to Treponema pallidum. The enzyme immunoassay format, with its potential for automation, is ideally suited for large volume batch testing. Five hundred eighty-five sera collected primarily from pediatric patients were subjected to rapid plasma reagin and DCL-G testing. The patients ranged in age from 1 day to 45 years (mean, 14.4 years). Sera yielding positive or equivocal results in duplicate by either method were tested further for T. pallidum immunoglobulin G and M antibodies by the fluorescent treponemal antibody absorbed test and the DCL Syphilis-M test kit. The sensitivity and specificity of DCL-G, considering the combined rapid plasma reagin and fluorescent treponemal antibody absorbed results as the reference, were 100% and 99.8%, respectively. It was concluded that the DCL-G assay was a simple, efficient, and accurate method for obtaining confirmed serologic evidence of past or present syphilis. PMID- 8447291 TI - Evaluation of modified MicroScan screening tests for high-level aminoglycoside resistance in Enterococcus faecalis. AB - Enterococcus faecalis strains that are refractory to aminoglycoside-penicillin synergistic killing can be predicted by their ability to grow in high concentrations of aminoglycoside (2,000 mg/L) or by disk diffusion tests using high content aminoglycoside disks. Forty-eight well-characterized clinical isolates of E. faecalis were used to evaluate recently reformulated gentamicin and streptomycin synergy screening tests on both overnight and rapid MicroScan (MS) Pos MIC panels (Baxter, West Sacramento, CA). The results obtained with the MS screening tests were compared with those from modified agar disk diffusion results. Discrepancies were resolved by an in-house broth microdilution method. The MS overnight tests detected 25 of 25 (100%) gentamicin high-level resistant strains and 23 of 24 (96%) streptomycin high-level resistant strains. No false high level resistance was found with the MS overnight tests. The MS rapid tests detected 100% of the gentamicin and 100% of the streptomycin high-level resistant strains, but one isolate was falsely high-level resistant to gentamicin (96% specific). The reformulated MS synergy screening tests were acceptable alternatives to disk diffusion for detection of high level aminoglycoside resistance in E. faecalis. PMID- 8447292 TI - Flow cytometric analysis of terminal deoxynucleotidyl transferase. A simplified method. AB - The authors evaluated a new cell membrane permeabilization method for the flow cytometric detection of terminal deoxynucleotidyl transferase (TdT). In this method, gradient-separated leukocytes or unseparated blood or bone marrow cells were incubated in a commercially available diethylene glycol-based red blood cell lysing solution, which not only lyses red blood cells, but also permeabilizes leukocyte cell membranes; the light scattering properties of the cells are retained. The validity of the current method was demonstrated by the good concordance of the findings with previously published data as follows: (1) practically identical results were obtained when an established method for cell permeabilization was used in parallel on the same samples; (2) the proportion of TdT-positive cells in normal peripheral blood was negligible; (3) the proportion of TdT-positive cells in normal bone marrow averaged 1%, and a significant portion of TdT-positive cells in normal bone marrow expressed CD10 and CD34; and (4) TdT-positive cell populations were seen with the expected frequencies in various types of leukemia. This method for TdT flow cytometry provides significant advantages over previously used methods and is especially suitable for TdT detection in routine laboratories. PMID- 8447293 TI - Histiocytic lymphadenitis associated with a large joint prosthesis. AB - Distinctive microscopic findings in enlarged axillary lymph nodes removed during modified radical mastectomy in a 76-year-old woman with a previous ipsilateral total shoulder joint replacement are described. The sinuses of the lymph nodes were distended by numerous large macrophages that had abundant granular eosinophilic cytoplasm. Periodic acid-Schiff staining was positive, and polarization microscopy revealed birefringent particles of polyethylene. These findings were diagnostic of the reactive lymphadenopathy that is seen uncommonly in lymph nodes draining large joint prostheses. PMID- 8447294 TI - The nature of Reed-Sternberg-like cells in chronic lymphocytic leukemia. AB - In biopsy specimens of B-cell chronic lymphocytic leukemia, large cells with cytologic features of Reed-Sternberg cells and mononuclear Hodgkin's cells are an uncommon occurrence. The nature of these large cells has not been fully elucidated, and the relationship of these cases with Hodgkin's disease is unclear. Immunophenotypic analysis of a case of chronic lymphocytic leukemia with interspersed Reed-Sternberg cells showed that the large cells were positive for CD45 (LCA), various B-cell markers (CD19, CD20, CD22), and CD30 (Ki-1), but were negative for CD15 (Leu-M1), suggesting that they represented activated neoplastic B cells. These results were compared with those reported in the literature. PMID- 8447296 TI - Muscle-actin antibodies. PMID- 8447295 TI - Platelet aggregation studies for the diagnosis of heparin-induced thrombocytopenia. AB - Heparin-induced thrombocytopenia (HIT) is a serious clinical disorder characterized by the sudden onset of thrombocytopenia and is often associated with paradoxic thrombosis in patients receiving heparin. The diagnosis of HIT has been hampered by problems with the laboratory methods used to establish the diagnosis. The authors evaluated the role of the source of heparin and donor platelets on the results of an ex vivo platelet aggregation assay for the diagnosis of HIT. Bovine lung and porcine mucosal heparins were equally effective at mediating ex vivo platelet aggregation induced by 17 of 17 known HIT-positive plasma samples. Plasma from 11 patients with a history of thrombocytopenia, exposure to heparin, and previously negative aggregation assays remained negative with both heparins on repeat testing. High concentrations of either heparin inhibited the aggregation response of normal platelets to HIT-positive samples but also inhibited the aggregation response of normal platelets to adenosine diphosphate (ADP) and collagen. Thus the inhibitory effect of high heparin concentrations was not specific for HIT. Platelets from different donors varied in their response to HIT-positive plasma and heparin; three donors were identified whose platelets did not respond to any HIT-positive plasma. The rest of the donors' platelets responded to HIT-positive plasma but varied in the degree of aggregation. These findings indicate that the source of heparin used for ex vivo assays does not affect the assay results but that selection of donors does have a significant impact on the outcome. Under appropriate conditions, platelet aggregation appears to be a sensitive and specific assay for the diagnosis of HIT. PMID- 8447297 TI - Desmoplastic small-cell tumor of the peritoneum with divergent differentiation: immunocytochemical and biochemical findings. PMID- 8447298 TI - Burkitt's lymphoma look-alike. PMID- 8447299 TI - Immunosuppressive drug therapy in lupus nephritis. AB - During the past two decades, the immunosuppressive drugs azathioprine and cyclophosphamide have been widely used in the treatment of patients with lupus nephritis. Their toxicities are well known and are mostly dose- and time dependent. Complications that arise from these therapies stem from their immunosuppressive (susceptibility for infection) or pharmacologic (hemorrhagic cystitis, bladder cancer, and fibrosis from the alkylating agents) effects, or both. Uncontrolled studies reporting good results in treating patients with various combinations of corticosteroids and azathioprine and, especially, cyclophosphamide cannot be conclusively confirmed by the few controlled clinical trials that are available for review. Part of the problem of inconclusiveness has to do with timing treatment to different phases of the disease and the vast heterogeneity of lupus nephritis. Although these immunosuppressive agents may have favorable effects on the overall activity of systemic lupus erythematosus, their long-term effects per se on renal disease are in question and could be attributed to lower prednisone dosage and better medical management of hypertension, hyperlipidemia, infection, and other metabolic consequences of the disease. PMID- 8447300 TI - Elevated levels of tumor necrosis factor-alpha in the nephrotic syndrome in humans. AB - To investigate the possible role of cytokines in the mediation of glomerular injury in the nephrotic syndrome, the levels of interleukin (IL)-1 beta, IL-2, interferon (IFN)-alpha, IFN-gamma, and tumor necrosis factor-alpha (TNF-alpha) were measured in patients with primary nephrotic syndrome. These patients had minimal change nephropathy (MCN), focal and segmental glomerulosclerosis (FSGS), or membranous nephropathy (MN) on biopsy. Cytokine levels were assessed by immunoradiometric assays, and specimens consisted of plasma, urine, and the culture supernate of mitogen-stimulated peripheral blood mononuclear cells (PBMC). Only TNF-alpha was found to be significantly elevated, in the plasma and urine of patients with FSGS and MN, above that found in healthy control subjects and patients with MCN. The elevation of TNF-alpha could not be shown to correlate with the length or severity of the nephrotic syndrome or with loss of body mass. IL-1 beta, IL-2, IFN-alpha, and IFN-gamma levels were not elevated. In culture, mitogen-stimulated PBMC from all three groups of nephrotic subjects released an excess of TNF-alpha compared with controls, a response not consistently observed for the other cytokines measured. The findings of this survey of cytokine levels in nephrotic patients support the possibility that TNF-alpha may play a pathogenic role in the induction or maintenance of glomerular barrier dysfunction in humans. PMID- 8447301 TI - Medical nephrectomy: the last resort for intractable complications of the nephrotic syndrome. AB - The large protein excretion of nephrotic syndrome leads to severe hypoalbuminemia and massive edema. The ensuing hyperlipidemia may not respond to any treatment unless protein losses are corrected. Urinary excretion of clotting factors due to nonselective proteinuria explains, at least in part, the development of a procoagulable state. We report herein four cases of intractable nephrotic syndrome that required medical nephrectomy by bilateral embolization of renal arteries. This procedure, although unusually performed, is an important therapeutic option in selected patients with nephrotic syndrome. PMID- 8447302 TI - An estimate of the size of the US predialysis population with renal insufficiency and anemia. AB - With the development of recombinant human erythropoietin, clinicians can now treat the anemia of chronic renal failure patients. Although most attention has focused on patients with end-stage renal disease, erythropoietin is also prescribed to anemic renal patients before the initiation of dialysis therapy. This study presents the first objective estimate of the size of the US population with predialysis renal insufficiency and the fraction of those patients who also have anemia. The study used population-based data from the second National Health Nutrition Examination Survey (NHANES II), conducted between 1976 and 1980. Participants underwent interviews, standardized physical examinations, and blood testing, including hematocrit and serum creatinine (N = 25,286 who were surveyed, 10,453 who underwent laboratory testing). Our estimates were based on the following methodology: (1) selecting predialysis renal insufficiency patients aged 12 to 74 years from the NHANES II survey, (2) adjusting for population changes between 1978 and 1988, (3) adding estimates for pediatric and geriatric populations, (4) projecting results to 1990, and (5) excluding nonanemic patients. The NHANES II survey included 44 patients with serum creatinine values greater than 2.0 mg/dL and less than 8.0 mg/dL. This yielded an estimate of 648,000 to 708,000 persons in 1990 with predialysis renal insufficiency. Data from both the NHANES II survey and the literature demonstrate that the percent of patients with anemia varies by serum creatinine level. All total, the study estimated that in 1990 there were between 68,000 and 75,000 individuals with predialysis renal insufficiency who also had anemia. However, several limitations of the methodology suggest that these values overestimate the true population numbers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447303 TI - A new vascular access catheter for hemodialysis. AB - A new vascular access catheter has been developed (Cook Critical Care, Bloomington, IN) that is suitable for both short-term and long-term hemodialysis. Designed primarily for the internal jugular vein, it emerges through a subcutaneous tunnel on the anterior chest wall. With parallel cylindrical lumens to provide blood flows of 400 mL/min, it is compressible during insertion and can be placed percutaneously in the vein through a 13-French peel-away sheath. This allows repeated insertions at different times in the same patient. In 80 catheter insertions, we have found one case of jugular vein thrombosis attributable to the catheter and no subclavian vein thrombosis. After 15 months of use, the bloodstream infection rate was one per 19.7 patient-months. Using this device, it should be possible to stop the subclavian vein damage and perforating injuries that have been the most important complications of semistiff, tapered, subclavian catheters. PMID- 8447304 TI - Superior vena cava stenosis associated with hemodialysis catheters. AB - The cases are described of four patients on long-term hemodialysis who developed stenosis of the superior vena cava (SVC) that interfered with the functioning or placement of jugular catheters for hemodialysis. All four patients had previously received multiple subclavian and/or jugular catheters inserted for hemodialysis access. In three patients, the SVC stenosis was successfully dilated by balloon angioplasty, and in one of these a stent was inserted to prevent restenosis. These three patients have subsequently been successfully dialyzed with jugular catheters. Stenosis of the SVC should be suspected when jugular catheters in the SVC give inadequate flows in the absence of thrombotic obstruction. Balloon dilatation with or without vascular stenting may allow satisfactory vascular access to be reestablished. PMID- 8447305 TI - High incidence of hepatitis C virus infection in hemodialysis patients in Taiwan. AB - A longitudinal follow up of 202 hemodialytic patients were conducted to evaluate the incidence of hepatitis C virus (HCV) infection in this high-risk group. A total of 113 patients were found to be seronegative for anti-HCV at the start of this study period. During the average follow-up period of 39 months, 51 patients developed anti-HCV later (group I), while the remaining 62 patients (group II) were seronegative throughout the study period. The results showed that the incidence of HCV seropositivity is 14.6% per year. Longer periods of hemodialysis and younger age of the patient, but not reuse of dialyzer or sex, were correlated with a higher positive rate of anti-HCV. Clinical hepatitis episodes occurred more frequently in group I (56.9%), while persistently normal alanine aminotransferase (ALT) was observed more often in group II (54.8%). There was no significant changes in hepatitis B surface antigen (HBsAg). A total of 41 patients developed hepatitis among the 59 patients who received transfusions, but there was no significant difference between the two groups. We conclude that HCV infection is the main cause of hepatitis in hemodialysis. The longer the patient underwent hemodialysis, the higher the anti-HCV positive rate became, which did not seem to be related to transfusions. Once infected, there is a low disappearance rate of anti-HCV. The exact route of transmission awaits further investigation. PMID- 8447306 TI - The relationship between serum calcitonin and calcium in the hemodialysis patient. AB - An increase in the serum calcium level is known to stimulate calcitonin secretion, but whether calcitonin contributes to calcium regulation in the dialysis patient is not known. Because we recently observed in the rat that (1) a sigmoidal calcitonin-calcium curve was present, and (2) calcitonin stimulation decreased the calcemic response to parathyroid hormone (PTH), the relationship between serum calcitonin and calcium was studied in six hemodialysis patients. To evaluate both the calcitonin-calcium and PTH-calcium relationships, hemodialysis with a low-calcium dialysate (2 mg/dL) was performed and followed 1 week later by hemodialysis with a high-calcium dialysate (8 mg/dL). The calcitonin-calcium relationship was best represented as a sigmoidal curve that was opposite in direction to the PTH-calcium curve. The range of the calcitonin-calcium curve was less than the PTH-calcium curve; as a percent of maximal, the minimal calcitonin was higher than the minimal PTH, 61% +/- 5% versus 26% +/- 4% (P < 0.001). As opposed to the PTH-calcium curve in which the basal PTH value was intermediate between the minimal and maximal PTH, the basal calcitonin value was close to the minimal calcitonin. Despite a wide range of ionized serum calcium concentrations (3.5 to 5.3 mg/dL), maximal stimulation was greater than maximal inhibition of calcitonin, 60% +/- 13% versus 3% +/- 2% (P = 0.01). Finally, a significant correlation was observed between basal and maximal calcitonin (r = 0.99, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447307 TI - The epidemiology of peritonitis in acute peritoneal dialysis: a comparison between open- and closed-drainage systems. AB - We performed a prospective study to examine the epidemiology and microbiology of peritonitis complicating acute intermittent peritoneal dialysis (IPD) performed in an in-hospital setting for the management of acute and chronic renal failure and to see the effect of a closed-drainage system on altering the frequency and cause of peritonitis. Over a 15-month period, 79 patients were treated with acute IPD for a total of 136 treatments each ranging in length from 2 to 40 days (median, 4 days). The majority of cases had acute renal failure (ARF; 65%) and were treated in intensive care units (ICUs; 74%) with serious comorbid conditions (60%). About half were treated with a two-bag, ventable (open)-drainage system with unprotected spikes, and the other half were treated with a single-bag, spike protected, closed-drainage system. There were 27 cases of peritonitis for a rate of 4.5 cases/100 patient-days at risk. About half were gram-positive infections; the remainder were gram-negative or mixed (25%) or Candida sp (25%). The use of a closed-drainage system reduced the incidence of system-related peritonitis from 3.6 to 1.5 cases/100 patient-days. There was a high rate of peritonitis in the first 48 hours of treatment, which fell to a low stable rate thereafter and remained so for up to 15 days of continuous IPD. The use of a closed-drainage system eliminated the early (< 48 hours) high rate of peritonitis and maintained a low constant rate of peritonitis throughout treatment. There was an association of ARF and severe comorbid disease with more virulent organisms (gram-negative, mixed, and Candida sp), which, in turn, were both associated with antecedent broad-spectrum antibiotic therapy. Random positive surveillance cultures showed a frequency distribution similar to that of peritonitis cases over the duration of treatment, but with less virulent organisms. Peritonitis in acute IPD occurs when large or repeated inocula of organisms from the prevailing flora overwhelm the peritoneal immune clearance mechanisms. Prolonged courses of broad-spectrum antibiotic therapy provide no protection, but shift the resulting infecting flora toward more virulent pathogens. A closed-drainage system provides one method to reduce the frequency of peritoneal contamination. PMID- 8447308 TI - Preeclampsia related to a functioning extrauterine placenta: report of a case and 25-year follow-up. AB - We report the case of a patient with preeclampsia due to an extrauterine, intra abdominal pregnancy. After the fetus was delivered, but while the functioning placenta remained in the abdomen, preeclampsia, which was documented by clinical data and a kidney biopsy, persisted until the placenta was removed 99 days postpartum. A kidney biopsy 21 months postpartum was normal. Twenty-five years later, her kidney function and blood pressure were normal. The observation of this patient supports the view that the placenta must be intact for the development of preeclampsia and is the first description of endotheliosis in a kidney biopsy from a hypertensive woman with an intra-abdominal pregnancy. PMID- 8447309 TI - Thrombotic thrombocytopenic purpura: evidence that infusion rather than removal of plasma induces remission of the disease. AB - Plasma exchange has recently been reported to be more effective than plasma infusion for the treatment of thrombotic thrombocytopenic purpura (TTP). However, in the only available controlled study, the plasma infused during the exchange procedure was three times that given by infusion alone. Here we report the case of a patient with chronic relapsing TTP who had 21 relapsing episodes in the last 3 years. During 18 relapses, infusion of plasma, as infusion alone or in the context of an exchange procedure, invariably induced remission of the disease. By contrast, plasma removal alone (replaced with albumin and saline) was ineffective in three further consecutive relapses so that infusion was eventually necessary to induce remission. We concluded that the effective component of plasma exchange in TTP is infusion, rather than removal of plasma. Unusually large von Willebrand factor (ULvWF) multimers were found during both acute and remission phases, possibly reflecting intravascular leakage from ongoing endothelial cell injury. A relative increase of the 176-kd fragment and a relative decrease of the 225-kd subunit were demonstrated during the acute phase, indicating in vivo proteolytic vWF fragmentation. Since in vitro evidence is available that such fragments of vWF induce platelet aggregation, it is speculated that protease inhibitors of normal plasma help restore normal vWF processing activity in the circulation, which explains remission of the disease associated with the plasma infusion. PMID- 8447310 TI - Peritonitis associated with disseminated Mycobacterium avium complex in an acquired immunodeficiency syndrome patient on chronic ambulatory peritoneal dialysis. AB - Chronic ambulatory peritoneal dialysis (CAPD) is a commonly used form of renal replacement therapy in patients with end-stage renal disease (ESRD) infected with the human immunodeficiency virus (HIV). An increased incidence of peritonitis, as well as an increased rate of infections with unusual and serious organisms, has been reported in these patients. We report the first case of an HIV-infected patient who developed clinical peritonitis associated with Mycobacterium avium intracellulare (MAI) infection. We suggest that the diagnosis of MAI peritonitis be suspected in HIV-infected patients with clinical CAPD peritonitis, negative cultures for bacteria or fungi, and a CD4 count less than 100 cells/microL. Therapy with a two-drug regimen for disseminated MAI infection without removal of the peritoneal dialysis (PD) catheter appears to provide symptomatic improvement while allowing ongoing PD. PMID- 8447311 TI - Deteriorating renal function with acetazolamide in a renal transplant patient with pseudotumor cerebri. AB - Treatment with acetazolamide for pseudotumor cerebri (PTC) in a renal transplant patient led to an acute, but reversible deterioration in renal function. Possible pathogenetic mechanisms behind acute renal failure and acetazolamide are detailed. In summary, caution should be exercised in all patients with chronic renal failure who require acetazolamide. It should be avoided if possible, used in reduced doses when necessary, and coupled with a high fluid intake to avoid dehydration and/or intraluminal obstruction. PMID- 8447312 TI - Sickle cell disease and the kidney. PMID- 8447313 TI - Flash pulmonary edema and the diagnostic suspicion of occult renal artery stenosis. PMID- 8447314 TI - Endothelial activation and the kidney: vasomediator modulation and antioxidant strategies. AB - We have come to appreciate that the endothelium plays a major role in regulation of renal hemodynamics and excretory function. In the normal state, the endothelium maintains an intricate balance of interacting relaxing and contracting factors that can influence vasomotor tone and renal sodium handling, but also plays a role in the control of the coagulation system and cellular proliferation. Studies of reactive oxygen species as mediators of endothelial injury have shown that the perturbed endothelium can respond to such a threat, calling on intrinsic protective mechanisms such as induction of heme oxygenase and ferritin synthesis. In vivo studies have demonstrated that these mechanisms may confer protection in experimental models of acute renal injury. However, when endothelial injury or dysfunction does occur, adverse renal hemodynamic consequences, systemic hypertension, enhanced platelet aggregation, and mesangial cell proliferation could all contribute to progressive renal dysfunction. The role of the endothelium in modulation of normal renal function and in the pathogenesis of renal diseases will be the focus of future research efforts. PMID- 8447315 TI - Familial IgA nephropathy associated with bilateral sensorineural deafness. PMID- 8447316 TI - Mutations in the paired domain of the human PAX3 gene cause Klein-Waardenburg syndrome (WS-III) as well as Waardenburg syndrome type I (WS-I). AB - Waardenburg syndrome type I (WS-I) is an autosomal dominant disorder characterized by sensorineural hearing loss, dystopia canthorum, pigmentary disturbances, and other developmental defects. Klein-Waardenburg syndrome (WS III) is a disorder with many of the same characteristics as WS-I and includes musculoskeletal abnormalities. We have recently reported the identification and characterization of one of the first gene defects, in the human PAX3 gene, which causes WS-I. PAX3 is a DNA-binding protein that contains a structural motif known as the paired domain and is believed to regulate the expression of other genes. In this report we describe two new mutations, in the human PAX3 gene, that are associated with WS. One mutation was found in a family with WS-I, while the other mutation was found in a family with WS-III. Both mutations were in the highly conserved paired domain of the human PAX3 gene and are similar to other mutations that cause WS. The results indicate that mutations in the PAX3 gene can cause both WS-I and WS-III. PMID- 8447317 TI - The molecular genetic basis of muscle phosphoglycerate mutase (PGAM) deficiency. AB - The glycolytic enzyme phosphoglycerate mutase (PGAM) is a dimer, and mature human skeletal muscle contains almost exclusively the MM form of the enzyme, PGAM-M. In 1981, we identified a patient with PGAM-M deficiency, and three additional patients have since been described. All presented with exercise intolerance, cramps, and myoglobinuria. We report two new patients with PGAM-M deficiency and describe the molecular lesions in five patients--four African-Americans and one Caucasian. Three patients were homozygous for an identical G-to-A transition converting an encoded Trp to an in-frame stop codon (codon 78). A fourth patient was heterozygous for this mutation and also carried an A-to-C mutation converting Glu to Ala (codon 89). The fifth patient, the only Caucasian, was homozygous for a different point mutation, a C-to-T mutation, converting Arg to Trp (codon 90). PMID- 8447318 TI - Transmission test for linkage disequilibrium: the insulin gene region and insulin dependent diabetes mellitus (IDDM). AB - A population association has consistently been observed between insulin-dependent diabetes mellitus (IDDM) and the "class 1" alleles of the region of tandem-repeat DNA (5' flanking polymorphism [5'FP]) adjacent to the insulin gene on chromosome 11p. This finding suggests that the insulin gene region contains a gene or genes contributing to IDDM susceptibility. However, several studies that have sought to show linkage with IDDM by testing for cosegregation in affected sib pairs have failed to find evidence for linkage. As means for identifying genes for complex diseases, both the association and the affected-sib-pairs approaches have limitations. It is well known that population association between a disease and a genetic marker can arise as an artifact of population structure, even in the absence of linkage. On the other hand, linkage studies with modest numbers of affected sib pairs may fail to detect linkage, especially if there is linkage heterogeneity. We consider an alternative method to test for linkage with a genetic marker when population association has been found. Using data from families with at least one affected child, we evaluate the transmission of the associated marker allele from a heterozygous parent to an affected offspring. This approach has been used by several investigators, but the statistical properties of the method as a test for linkage have not been investigated. In the present paper we describe the statistical basis for this "transmission test for linkage disequilibrium" (transmission/disequilibrium test [TDT]). We then show the relationship of this test to tests of cosegregation that are based on the proportion of haplotypes or genes identical by descent in affected sibs. The TDT provides strong evidence for linkage between the 5'FP and susceptibility to IDDM. The conclusions from this analysis apply in general to the study of disease associations, where genetic markers are usually closely linked to candidate genes. When a disease is found to be associated with such a marker, the TDT may detect linkage even when haplotype-sharing tests do not. PMID- 8447319 TI - Genetic heterogeneity of glucose-6-phosphate dehydrogenase deficiency revealed by single-strand conformation and sequence analysis. AB - We have carried out a systematic study of the molecular basis of glucose-6 phosphate dehydrogenase (G6PD) deficiency on a sample of 53 male subjects from Calabria, in southern Italy. Our sequential approach consisted of the following steps: (1) Partial biochemical characterization was used to pinpoint candidate known variants. The identity of these was then verified by restriction-enzyme or allele-specific oligonucleotide hybridization analysis of the appropriate PCR amplified fragment. (2) On samples for which there was no obvious candidate mutation, we proceeded to amplify the entire coding region in eight fragments, followed by single-strand conformation polymorphism (SSCP) analysis of each fragment. (3) The next step was M13 phage cloning and sequencing of those individual fragments that were found to be abnormal by SSCP. Through this approach we have identified the molecular lesion in 51 of the 53 samples. In these we found a total of nine different G6PD-deficient variants, five of which (G6PD Mediterranean, G6PD A-, G6PD Coimbra, G6PD Seattle, and G6PD Montalbano) were already known, whereas four are new (G6PD Cassano, G6PD Cosenza, G6PD Sibari, and G6PD Maewo). G6PD Mediterranean is the commonest variant, followed by G6PD Seattle. At least seven of the variants are present, at polymorphic frequencies, in the Calabria region, and some have a nonrandom distribution within the region. This study shows that the genetic heterogeneity of G6PD deficiency in Calabria, when analyzed at the DNA level, is even greater than had been anticipated from biochemical characterization. The sequential approach that we have followed is fast and efficient and could be applied to other populations. PMID- 8447320 TI - Further evidence for a locus for cutaneous malignant melanoma-dysplastic nevus (CMM/DN) on chromosome 1p, and evidence for genetic heterogeneity. AB - Assignment of a susceptibility locus for cutaneous malignant melanoma-dysplastic nevus (CMM/DN) to chromosome 1p remains controversial. We examined the relationship between CMM/DN and markers D1S47, PND, and D1S160 on seven new families (set B) plus updated versions of six previously reported families (set A). Three linkage analyses were performed: (1) CMM alone--all individuals without confirmed melanoma or borderline lesions were considered unaffected (model I); (2) CMM/DN with variable age at onset and sporadics (model II); and (3) CMM/DN using the model of Bale et al. (model III). For CMM alone and D1S47, Zmax = 3.12 at theta = .10. For D1S160 and CMM alone, Zmax = 1.76 at theta = .10. PND showed no evidence for linkage to CMM alone. Models II and III showed strong evidence for linkage to D1S47, D1S160, and PND in the set A pedigrees but not in the set B families. We tested for homogeneity of CMM/DN (model II) by splitting families into two groups on the basis of (1) the proportion of CMM/DN cases and (2) the occurrence of immune-related tumors. In group 1 there was significant evidence of heterogeneity with both D1S47 and D1S160, and in group 2 there was significant evidence of heterogeneity with D1S160. Thus, diagnostic, clinical, and genetic heterogeneity are the likely reasons that previous studies have failed to confirm linkage of CMM/DN to chromosome 1p. The results showed significant evidence for a CMM locus linked to D1S47, as well as significant evidence for heterogeneity with only a subset of the families appearing linked to chromosome 1p. PMID- 8447321 TI - Multiple symmetric lipomas with high levels of mtDNA with the tRNA(Lys) A- >G(8344) mutation as the only manifestation of disease in a carrier of myoclonus epilepsy and ragged-red fibers (MERRF) syndrome. AB - We have investigated the morphology, cytogenetics, and the fraction of mtDNA with the tRNA(Lys) A-->G(8344) mutation in three lipomas in a carrier of this mutation. The son of the patient had myoclonus epilepsy and ragged-red fibers syndrome. The fraction of mtDNA with the tRNA(Lys) mutation varied between 62% and 80% in cultured skin fibroblasts, lymphocytes, normal adipose tissue, and muscle. In the three lipomas the mean fraction of mutated mtDNA was 90%, 94%, and 94%. Ultrastructural examination of the lipomas revealed numerous mitochondria with changes such as electron-dense inclusions in some adipocytes. When considered cytogenetically, the lipomas were characterized by a mixture of karyotypically abnormal and normal cells. An identical del(6)(q24) was found in two tumors. The fraction of mutated mtDNA in cultured lipoma cells was the same as in the lipoma in situ, indicating that the cultured cells were representative of the primary tumor. These findings indicate that the lipomas have originated with a grossly normal stem line and subsequently have developed the 6q deletion. We conclude that the lipomas represent clonal growth of adipocytes with a high content of mtDNA with the tRNA(Lys) mutation. The tRNA(Lys) mutation may be either the direct or the indirect cause of pertubation of the maturation process of the adipocytes, leading to an increased risk of lipoma formation. PMID- 8447322 TI - Insurance and genetic testing: where are we now? AB - Basic research will spur development of genetic tests that are capable of presymptomatic prediction of disease, disability, and premature death in presently asymptomatic individuals. Concerns have been expressed about potential harms related to the use of genetic test results, especially loss of confidentiality, eugenics, and discrimination. Existing laws and administrative policies may not be sufficient to assure that genetic information is used fairly. To provide factual information and conceptual principles upon which sound social policy can be based, the Human Genome Initiative established an Ethical, Legal, and Social Issues Program. Among the first areas to be identified as a priority for study was insurance. This paper provides a review of life, health, and disability insurance systems, including basic principles, risk classification, and market and regulatory issues, and examines the potential impact of genetic information on the insurance industry. PMID- 8447325 TI - Is there heterogeneity of age at onset for breast cancer? PMID- 8447323 TI - True hermaphroditism in a 46,XY individual, caused by a postzygotic somatic point mutation in the male gonadal sex-determining locus (SRY): molecular genetics and histological findings in a sporadic case. AB - Recently, the gene for the determination of maleness has been identified in the sex-determining region on the short arm of the Y chromosome (SRY) between the Y chromosomal pseudoautosomal boundary (PABY) and the ZFY gene locus. Experiments with transgenic mice confirmed that SRY is a part of the testis-determining factor (TDF). We describe a sporadic case of a patient with intersexual genitalia and the histological finding of ovotestes in the gonad, which resembles the mixed type of gonadal tissue without primordial follicle structures. The karyotype of the patient was 46,XY. By PCR amplification, we tested for the presence of PABY, SRY, and ZFY by using DNA isolated from peripheral blood leukocytes and for the presence of SRY by using DNA obtained from histological gonadal slices. The SRY products of both DNA preparations were further analyzed by direct sequencing. All three parts of the sex-determining region of the Y chromosome could be amplified from leukocytic DNA. The patient's and the father's SRY sequences were identical with the published sequence. In the SRY PCR product of gonadal DNA, the wild-type and two point mutations were present in the patient's sequence, simulating a heterozygous state of a Y-chromosomal gene: one of the mutations was silent, while the other encoded for a nonconservative amino acid substitution from leucine to histidine. Subcloning procedures showed that the two point mutations always occurred together. The origin of the patient's intersexuality is a postzygotic mutation of the SRY occurring in part of the gonadal tissue. This event caused the loss of the testis-determining function in affected cells. PMID- 8447324 TI - Libraries for each human chromosome, constructed from sorter-enriched chromosomes by using linker-adaptor PCR. AB - We describe here the production of complex libraries enriched in sequences from each human chromosome type, starting with only a few thousand sorter-purified chromosomes. In this procedure, DNA is extracted from the sorted chromosomes, digested to completion by using the frequently cutting restriction endonuclease Sau3A1, and ligated, on each end, to an adaptor oligonucleotide. These fragments are then amplified using PCR with a sequence homologous to the adaptor oligonucleotide as a primer. We have used this procedure to produce PCR libraries for each of the 24 human chromosomes. These libraries were characterized by gel electrophoresis and found to be composed of a continuum of sequences ranging in size from a few hundred to approximately 1,000 bp. The libraries, when used as probes for fluorescence in situ hybridization, stained the target chromosomes more or less continuously, even after PCR amplification for more than 200 cycles. These libraries are useful as hybridization probes to facilitate molecular cytogenetic studies and as sources of probes either for identification of polymorphic short tandemly repeated sequences or for development of sequence tagged sites. PMID- 8447326 TI - When single-stranded conformations are polymorphic. PMID- 8447327 TI - Further considerations of Caucasian admixture. PMID- 8447328 TI - Looking back, looking ahead. PMID- 8447329 TI - Students online: learning medical genetics. AB - It is possible to focus medical genetics education by using a model that integrates the skills of end-user searching of the medical literature into the traditional course content. Since 1988, 313 first-year medical students were studied as they accessed MEDLINE to retrieve information about biochemical genetic disorders. Their search behavior was studied by analyzing data from the National Library of Medicine's traffic files. The skills that they initially learned were reinforced as they searched clinical genetics problem cases in the second-year pathology course, and these skills were consolidated in the third year when the students addressed specific patient-care questions in pediatrics. The students' perception of the value of this model was studied by analyzing questionnaires completed during the exercise. It was demonstrated that when students were taught the skills of accessing MEDLINE by computer, they could formulate a question, retrieve current information, critically review relevant articles, communicate effectively, and use these skills to contribute to patient care. PMID- 8447330 TI - The survival of eugenics in 20th-century Germany. PMID- 8447331 TI - Historiography of eugenics. PMID- 8447332 TI - Plasma lipid concentrations and subsequent coronary occlusion after a first myocardial infarction. The POSCH Group. AB - This study correlated plasma lipid values with angiographic evidence of progression to complete coronary occlusion. Baseline triglycerides (TGs), total cholesterol (Chol), high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, and HDL/LDL and HDL/Chol ratios were compared with coronary angiograms taken at baseline, 3 and 5 years in a prospective angiographic study. Results were from part of the multicenter trial of plasma lipid reduction in patients after a single myocardial infarction (POSCH). Comparison of patient's baseline lipids in the absence or presence of a new total coronary occlusion at 3 years showed a significant difference (p = 0.01) in TGs of 197 +/- 147 versus 250 +/- 162 mg/dl (p = 0.02) and VLDL of 30 +/- 23 (n = 284) versus 40 +/- 30 (n = 49) mg/dl. Stratification by the mean HDL/Chol ratio (16%) demonstrated that baseline TG levels were significantly increased in patients with a new coronary occlusion by 3 years despite a higher HDL/Chol ratio. When measured at the 3-year visit, plasma TG (176 +/- 91 versus 212 +/- 146 mg/dl; p = 0.02) and VLDL (28 +/- 18 versus 35 +/- 29 mg/dl; p = 0.04) were significantly elevated in the presence of a new 3-year coronary occlusion. Stratification by the mean HDL/Chol ratio (16%) demonstrated that 3-year TG levels increased significantly in patients with a new 3-year coronary occlusion despite a higher HDL/Chol ratio.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447333 TI - The value of baseline chest radiograph reports in the care of elderly patients in an emergency department. AB - The authors used a before/after research design to determine the impact of written reports of baseline chest radiographs (CXRs) on the care of elderly patients during 48 emergency department visits. Internal medicine housestaff completed questionnaires that included inquiries about their treatment plans for the patients both before and after they reviewed reports of baseline CXR results. The investigators compared these answers to determine the proportion of patients for whom baseline CXR reports changed patient management. In addition, three faculty reviewers used the nominal group process, a consensus analysis approach, to measure treatment changes and to estimate benefit to the patients from the alterations in management. The housestaff indicated that written baseline CXR reports caused them to change treatment plans during only 2 (4%) of the 48 visits. In both cases, they provided aggressive treatment for congestive heart failure because of baseline CXR results. The faculty reviewers could find only one case in which baseline CXR findings might have changed their management plans. Moreover, they were not convinced that the treatment changes indicated by the housestaff actually benefitted the patients. These results suggest that written reports of baseline CXRs do not improve the care of acutely ill patients in an emergency department setting. PMID- 8447334 TI - Is "relative" hypertension a risk factor for vaso-occlusive complications in sickle cell disease? AB - Supine arterial blood pressure measurements of 89 patients with homozygous sickle cell disease and normal renal function were compared with those of an age-, race , and sex-matched normal population and with those of individuals who had similar levels of anemia due to beta thalassemia. Consistent with previous reports, sickle cell patients had significantly lower blood pressure than the normal population. However, within most age groups, sickle cell patients tended to have higher than expected blood pressure than individuals with similar or less severe degrees of anemia. Furthermore, the authors have found an association between cerebrovascular accident and elevated blood pressure in men, even in a range of systolic and diastolic pressures that would be considered normal by conventional standards. These results reiterate the intricate relationship that exists between factors governing red cell rheology and microvascular tone. They also raise the possibility that "relative" hypertension may be associated with other vaso occlusive manifestations of the sickle cell syndromes. PMID- 8447335 TI - Case report: potentiation of warfarin by fluconazole. AB - Described is an elderly woman who developed gastrointestinal bleeding probably potentiated by the interaction of fluconazole with warfarin. Because varied clinical uses are being found for fluconazole, clinicians should be aware of this potential interaction. PMID- 8447336 TI - Case report: left ventricular apical hypertrophy in progressive limb-girdle muscular dystrophy. AB - Cardiac involvement is uncommon in patients with limb-girdle muscular dystrophy. This report describes a patient in whom concentric hypertrophy localized to the apical left ventricle was revealed during a long clinical course of skeletal muscular dystrophy, with evolving electrocardiographic changes also compatible with apical hypertrophic cardiomyopathy. Endomyocardial biopsy revealed similar histologic changes in the skeletal muscle biopsy specimen, characterized by muscle fiber atrophy and hypertrophy with a mild degree of interstitial fibrosis. The pathogenesis of cardiac hypertrophy in this case is unclear. However, the pathologic findings suggest that the myocardium may be involved in the same dystrophic process as the skeletal muscles. PMID- 8447337 TI - Case report: Yersinia enterocolitica necrotizing pneumonia in an immunocompromised patient. AB - The authors report a rare case of Yersinia enterocolitica necrotizing pneumonia in an immunocompromised patient, who responded with resolution of the infection after 6 weeks of therapy with a third-generation cephalosporin but subsequently expired from the underlying lymphoma. In the few cases of Y. enterocolitica pulmonary infections that have been reported, the prognosis for cure of the infection is excellent with appropriate antibiotic therapy. Y. enterocolitica is likely to be recognized more frequently as a cause of serious infection in the growing immunosuppressed population. Early recognition and appropriate therapy can improve survival significantly. PMID- 8447338 TI - Case report: nuclear magnetic resonance imaging in a patient with a pacemaker. AB - The presence of a pacemaker has been considered a contraindication for magnetic resonance imaging (MRI) examination. The authors describe a patient with a pacemaker who underwent MRI of the head without sequelae. Spine-echo MRI was preformed with 1.5 Tesla imager using head coil only. Prior to imaging, the pacemaker was programmed to the OOO mode. In carefully selected pacing independent patients, with a pacemaker in a bipolar configuration, MRI of the head appears to be safe provided the pacemaker is programmed to OOO and enough scar tissue has developed to prevent pacemaker or lead movement. PMID- 8447339 TI - The promises and perils of treating the elderly hypertensive. AB - Recently published clinical trials have shown clear benefits of the treatment of hypertension in the elderly. Therefore, millions of elderly patients will be considered in need of antihypertensive therapy. In addition to the promises that such therapy offer, there are multiple perils involved in the treatment of elderly patients. PMID- 8447340 TI - Unsafe nursing. PMID- 8447341 TI - Ways to probe for substance abuse. PMID- 8447342 TI - Choosing mental health. PMID- 8447343 TI - Implementing the Patient Self-Determination Act. PMID- 8447344 TI - Trend-spotting with an SvO2 monitor. PMID- 8447345 TI - How to ask drug companies for help. PMID- 8447347 TI - Spinal-cord compression. Early detection may avert paralysis. PMID- 8447346 TI - Troubleshooting a sump tube. PMID- 8447348 TI - Our unit has a bereavement program. PMID- 8447349 TI - Decoding the messages of the dying. PMID- 8447350 TI - Clue: unusually severe wound pain. PMID- 8447351 TI - Fear of contracting AIDS is reason enough. PMID- 8447352 TI - Suddenly seeing me. PMID- 8447353 TI - Selectivity information on desogestrel. AB - Improvement in oral contraceptive formulations was originally achieved through dose reduction of the estrogen and progestogen components. Recently, further improvement was achieved by increasing the selectivity of contraceptive progestins. The ratio between the affinity for the progesterone receptor and the affinity for the androgen receptor is an indicator of progesterone (or androgen) selectivity of a progestin. This ratio (selectivity index) reflects the relative amount of androgenic or progestational effect at a given dose. Relative selectivity can be characterized with in vitro receptor-binding studies and animal pharmacologic experiments. In comparison with levonorgestrel, desogestrel displays markedly lower androgenicity and slightly increased relative progestational activity. In receptor-binding experiments and animal pharmacologic studies, 3-keto-desogestrel, the active metabolite of desogestrel, shows the highest selectivity index. The favorable effect of desogestrel-containing oral contraceptives on lipoprotein metabolism and preexisting androgen-dependent skin disorders and the absence of adverse effects on blood pressure and body weight are attributed to the increased progestin selectivity of desogestrel. PMID- 8447354 TI - Contraceptive efficacy of a monophasic oral contraceptive containing desogestrel. AB - Desogestrel, a new gonane progestin, has been shown to be comparable in efficacy with oral contraceptives currently in use in the United States. Results from several large efficacy studies conducted in Europe encompassing 42,640 patients in 183,212 cycles resulted in six pregnancies for a Pearl index of 0.04. This low rate, which was compared with those observed in recent U.S. clinical trials, reflects differences in study methodology. An additional indicator of an oral contraceptive's efficacy is its ability to suppress ovarian function, including follicular development and increases in plasma estradiol levels. Desogestrel has been found to be among the strongest suppressors of ovarian activity. PMID- 8447355 TI - Pharmacokinetics of desogestrel. AB - A synthetic form of desogestrel, a gonane progestin, was developed because desogestrel's enhanced selectivity eliminates adverse, androgen-dependent, metabolic effects at contraceptive doses. Desogestrel is rapidly and completely metabolized in the liver and gut wall to 3-keto-desogestrel, which is the active metabolite mediating the progestin effects. Because of its unique 11-methylene side chain, desogestrel cannot be metabolized to any other known progestin, nor is desogestrel a naturally occurring metabolite of any other progestin. The pharmacokinetic parameters of 3-keto-desogestrel are generally comparable with those of levonorgestrel and norethindrone. Therefore any differences in pharmacologic activities must be attributed to differences in intrinsic activities. Unlike gestodene, 3-keto-desogestrel has a lower affinity for sex hormone-binding globulin, which results in markedly lower plasma levels after administration. After oral administration of 150 micrograms of desogestrel, plasma levels are less than half the levels of gestodene after an oral dose of 75 micrograms. PMID- 8447356 TI - Combined oral contraception with desogestrel/ethinyl estradiol: tolerability profile. AB - Since their introduction nearly 30 years ago, oral contraceptives have been widely researched regarding their contraceptive and noncontraceptive effects. With proper usage, oral contraceptives provide highly effective contraception. In addition, oral contraceptives confer significant noncontraceptive health benefits, including prevention of ovarian and endometrial cancer and reduction in the incidence of pelvic inflammatory disease, endometriosis, benign breast disease, and dysmenorrhea, among others. Today's low-dose oral contraceptives have an improved safety profile when contrasted with their early higher dose counterparts. Yet oral contraceptive use continues to be associated with a variety of minor side effects, which range from menstrual changes such as breakthrough bleeding, spotting, or amenorrhea, to androgenic effects, including weight gain and acne. These androgenic effects are important factors in patient discontinuation of oral contraceptives. Progestins with increased selectivity have the potential to cause fewer androgenic side effects while retaining appropriate progestin suppression of the endometrium and hypophyseal-pituitary ovarian axis. A combination oral contraceptive (30 micrograms of ethinyl estradiol with 150 micrograms of desogestrel) has been evaluated extensively by European investigators. This literature suggests that a low-dose oral contraceptive formulated with the selective progestin desogestrel offers a favorable profile of reduced androgenic side effects while retaining the cycle control associated with low-dose oral contraceptives currently marketed in the United States. PMID- 8447357 TI - Lipid metabolism effects with desogestrel-containing oral contraceptives. AB - Desogestrel is a gonane progestogen that in early studies had an improved ratio between desired progestational effects and undesired androgenic effects. A review of more than 50 clinical studies suggests that desogestrel differs from progestins currently used in oral contraception in that it does not interfere with the estrogen effects on lipoprotein metabolism. This profile is attributable to the high selectivity of desogestrel. PMID- 8447358 TI - Effects of desogestrel on carbohydrate metabolism. AB - Associated with progesterone and the synthetic progestins used in oral contraceptives is a dose-dependent impairment of carbohydrate metabolism. It is well known that in the general population hyperinsulinemia and alterations in glucose metabolism are significant risk factors for the development of cardiovascular disease. Studies that use curve analysis of glucose tolerance tests have demonstrated insulin resistance, rises in plasma insulin, and relative glucose intolerance in women using oral contraceptives. Desogestrel, a new progestin, has been demonstrated to have generally less pronounced effects on these parameters of carbohydrate metabolism. PMID- 8447359 TI - The effects on hemostasis of oral contraceptives containing desogestrel. AB - Epidemiologic research has shown that current low-dose estrogen oral contraceptives are associated with a low risk of vascular events (e.g., myocardial infarction, stroke, and venous thrombosis or thromboembolism). Yet questions still persist about the effects of low-dose oral contraceptives on the cardiovascular system. Changes in the coagulation system have been linked primarily to the estrogen component; however, it has been proposed that the progestin may have an influence on the fibrinolytic system. Desogestrel, a new gonane progestin, has been commercially available in Europe since 1981. It has been widely shown to produce minimal changes of the coagulation and fibrinolytic systems, and it has not been associated with an increased risk of thromboembolic disorders. PMID- 8447360 TI - Cation transport and volume regulation in sickle red blood cells. AB - Cellular dehydration is one of several pathological features of the sickle cell. Cation depletion is quite severe in certain populations of sickle cells and contributes to the rheological dysfunction that is the root cause of vascular occlusion in this disease. The mechanism of dehydration of sickle cells in vivo has not been ascertained, but three transport pathways may play important roles in this process. These include the deoxygenation-induced pathway that permits passive K+ loss and entry of Na+ and Ca2+; the K(+)-Cl- cotransport pathway, activated by acidification or cell swelling; and the Ca(2+)-activated K+ channel, or Gardos pathway, presumably activated by deoxygenation-induced Ca2+ influx. Recent evidence suggests that these pathways may interact in vivo. Heterogeneity exists among sickle cells as to the rate at which they become dense, suggesting that other factors may affect the activity or interactions of these pathways. Understanding the mechanism of dehydration of sickle cells may provide opportunities for pharmacological manipulation of cell volume to mitigate some of the symptoms of sickle cell disease. PMID- 8447361 TI - Metabolism of extracellular adenine nucleotides by human endothelial cells exposed to reactive oxygen metabolites. AB - Endothelial cells have ectonucleotidases that rapidly catabolize extracellular nucleotides. Our aim was to study whether the metabolism of extracellular nucleotides and adenosine are influenced by exposure of endothelial cells to reactive oxygen metabolites at concentrations relevant to human pathology. Human umbilical vein endothelial cells were incubated with hypoxanthine (100 microM) and xanthine oxidase (80 mU/ml), to generate superoxide, or with hydrogen peroxide (100 microM). The cells were then washed, and the metabolism of radioactive substrates was followed. After exposure to hypoxanthine-xanthine oxidase the half time of disappearance of [14C]ATP (5 microM) was prolonged from 9.9 +/- 5 to 28.3 +/- 15.6 min and that of [14C]AMP from 9.5 +/- 2.5 to 25.0 +/- 9.9 min. The conversion of extra- into intracellular nucleotides via adenosine was also decreased (mean for [14C]ATP 0.25 vs. 0.90 and for [14C]AMP, 0.075 vs. 0.75 nmol/10(6) cells in 30 min compared with parallel controls, respectively). Hydrogen peroxide or trypsin had no significant effect on the metabolism of extracellular adenine nucleotides and neither did a short (up to 15 min) exposure to the superoxide-generating system. The conversion of [14C]adenosine into intracellular nucleotides and hypoxanthine was not influenced by either hypoxanthine-xanthine oxidase or by hydrogen peroxide. We conclude that superoxide radicals inhibit the catabolism of extracellular adenine nucleotides by the ectonucleotidases of endothelial cells and may thus modify the pathophysiology of ischemia-reperfusion injury. PMID- 8447362 TI - 1,25-Dihydroxyvitamin D3 inhibits Na(+)-dependent phosphate transport in osteoblastic cells. AB - In the present work we investigated the influence of vitamin D3 metabolites on Na(+)-dependent phosphate (Pi) transport in the clonal osteoblastic cell line UMR 106. The vitamin D3 metabolite 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] dose dependently inhibited Pi transport with a half-maximal concentration of approximately 5 x 10(-11) M. The effect of 1,25(OH)2D3 was first observed after 8 h of preincubation period. Inhibition of phosphate uptake was relatively specific for the 1,25(OH)2D3 analogue of vitamin D3. The potency order was 1,25(OH)2D3 >> 24,25-dihydroxyvitamin D3 > 25-[3H]hydroxyvitamin D3. Kinetically, 1,25(OH)2D3 decreased the maximal velocity of the phosphate uptake system, whereas the affinity for phosphate was unaffected. Activation of protein kinase C (PKC) in UMR-106 cells stimulated Na(+)-dependent Pi transport. Nonetheless, the inhibitory effect of 1,25(OH)2D3 on Pi transport was not related to downregulation of PKC. Chemical determination of intracellular Pi showed a 50% reduction after 24-h preincubation with 10(-8) M 1,25(OH)2D3. We conclude that 1,25(OH)2D3 inhibits Na(+)-dependent phosphate transport in osteoblastic cells. This in turn leads to intracellular Pi depletion. The physiological implication of this phenomenon on the effects of vitamin D on osteoblasts in situ is discussed. PMID- 8447363 TI - Internalization and intracellular transport of folate-binding protein in rat kidney proximal tubule. AB - Folate-binding protein (FBP) is involved in folate reabsorption in the renal proximal tubule. Immunocytochemical studies have located FBP to the brush-border membrane, endocytic vacuoles, and dense apical tubules. We applied the same polyclonal antibody (anti-FBP) against FBP to investigate the dynamic relationship between FBP in the different compartments by microinjecting the antibody into rat kidney proximal tubules in situ. Specific binding of anti-FBP in vivo to the brush-border membrane was followed by fixation at various times. Protein A-gold labeling shows that anti-FBP is transported from endocytic invaginations into vacuoles followed by transport into dense apical tubules within 15 s. Thus FBP is rapidly internalized, and together with previous studies this study strongly suggests recycling of FBP back to the luminal plasma membrane through dense apical tubules. The results are consistent with reabsorption of folate through endocytosis of the FBP-folate complex followed by dissociation and recycling of FBP. When time is allowed there is a steady accumulation of FBP in dense apical tubules combined with an increase in surface density of the same compartment. A possible explanation involves partial inhibition of the fusion between dense apical tubules and plasma membrane because of the anti-FBP labeling of the receptor. PMID- 8447364 TI - Corticosterone induces 11 beta-HSD and mineralocorticoid specificity in an amphibian urinary bladder cell line. AB - We have examined the mineralocorticoid specificity in a TBM 18-23 cell line derived from the toad bladder epithelium. In cells grown on porous substrate, corticosterone was more potent than aldosterone in stimulating a sodium transport response, measured by the short-circuit current method 6 h after hormone addition [mean affinity constant (K0.5) for corticosterone = 1 nM vs. K0.5 for aldosterone = 8 nM]. The time course of effects and saturation kinetics were identical for both agonists, suggesting interaction with identical receptors. Whereas the dose response relationship for aldosterone did not change with time of incubation (6 vs. 24 h), the dose-response curve for corticosterone became biphasic at 24-h incubation (apparent K0.5 as high as 40 nM), demonstrating that corticosterone became apparently less potent with time. Pretreatment with carbenoxolone, a potent inhibitor of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), restored full sensitivity at 24-h incubation to corticosterone. The 11 beta-HSD activity was low during the first 3 h of incubation in the presence of 3 nM corticosterone, and only a small fraction (approximately 7%) of corticosterone was metabolized. At 24-h incubation, 11 beta-HSD activity increased approximately 2.5-fold (P < 0.001, n = 8). We conclude that 11 beta-HSD activity is induced by its own substrate in TBM cells in parallel with the induction of the carbenoxolone-sensitive sodium transport response. PMID- 8447365 TI - Extracellular matrix-stimulated phospholipase activation is mediated by beta 1 integrin. AB - beta 1-Integrins are major mediators of interactions between cells and extracellular matrix (ECM). Adhesion of rat glomerular epithelial cells (GEC) to collagen stimulated phospholipase C. As a result, 1,2-diacylglycerol (DAG) was increased, and inositol phospholipids were decreased in collagen-adherent cells, as compared with GEC adherent to plastic substrata. Adhesion to collagen also stimulated production of free arachidonic acid (the precursor for eicosanoids) due to metabolism of DAG through the DAG lipase pathway and due to phospholipase A2-induced hydrolysis of phospholipids. Phospholipase A2 appeared to be stimulated as a result of protein kinase C (PKC) activation, probably secondary to increased DAG. The collagen-induced increases in DAG and free arachidonic acid, as well as the decrease in inositol phospholipids, were partially inhibited by lowering extracellular Ca2+ concentration to 200 nM or less and by anti-beta 1 integrin antibody Fab. In contrast, anti-beta 1-integrin immunoglobulin G (IgG) enhanced collagen-mediated increases in DAG and arachidonic acid. Proliferation of GEC adherent to collagen was reduced in the presence of anti-beta 1-integrin IgG. The antiproliferative effect of anti-beta 1-IgG appeared to be mediated through PKC, since it was absent in PKC-depleted GEC. Immunoprecipitation with integrin subunit-specific antibodies demonstrated alpha 2 beta 1- and alpha 3 beta 1-integrins in GEC. Thus, in GEC, ECM induces activation of phospholipases C and A2, which is mediated, at least in part, by beta 1-integrins. Products of integrin-mediated phospholipase activation may modulate GEC proliferation. PMID- 8447366 TI - Molecular cloning and quantification of sarcoplasmic reticulum Ca(2+)-ATPase isoforms in rat muscles. AB - A cDNA encoding the full-length adult rat fast-twitch muscle Ca(2+) adenosinetriphosphatase (ATPase) was cloned. The deduced amino acid sequence of this molecule has 97 and 90% identity with those of rabbit fast-twitch muscle and chicken skeletal muscle Ca(2+)-ATPases, respectively. Specific probes from the 3' untranslated region of each sarcoplasmic or endoplasmic reticulum Ca(2+)-ATPase (SERCA) gene product and full-length cRNA transcript standards were used to determine the quantity of mRNA encoding each isoform in various rat muscles. Quantitative immunoblotting was also used to determine the protein content of each SERCA isoform. Fast-twitch fibers expressed both SERCA1 mRNA and protein at a level two- to fivefold higher than SERCA2 was expressed in slow-twitch fibers. We observed a protein-to-mRNA ratio that varied from approximately 500,000 molecules per molecule in the fast-twitch muscles to approximately 200,000 in cardiac and smooth muscles. There was no difference, however, between the ratio for different isoforms in the same muscle. The content of Ca2+ pump in a given muscle therefore depends on at least three factors: 1) the efficiency of gene transcription and message stability (fiber type dependent), 2) the efficiency of translation and protein stability (muscle identity dependent), and 3) fiber composition of the muscle. PMID- 8447367 TI - Desensitization and reactivation of ACh-regulated exocrine secretion in hen tracheal epithelium. AB - We have studied acetylcholine (ACh) desensitization of Cl- secretion and its reactivation by atropine in the hen tracheal epithelium employing voltage-clamp technique. Adding 4 microM ACh to the serosal side induces a maximal bumetanide sensitive Cl- secretion. The ACh-induced Cl- secretion is desensitized nearly 100% at 512 microM ACh. The desensitization of Cl- secretion may be reduced 30 40% by 0.32 microM atropine (reactivation). From a kinetic model for desensitization and reactivation with two muscarinic receptors (mAChR), we have estimated the maximal secretory response, the apparent dissociation coefficients, and the apparent Hill coefficients for ACh and atropine at the two receptors. Based on the kinetic model we can predict an optimal fixed concentration ratio (Ofcor) between ACh and atropine that will maintain Cl- secretion above 40% of maximum over a wide concentration range, ACh 1-4,100 microM, and we have confirmed the predicted Ofcor experimentally. A cellular model is proposed with two mAChR, one stimulatory and another inhibitory, that accounts for an observed dissociation between desensitization in short-circuit current and conductance. PMID- 8447368 TI - Effect of membrane potential on K-Cl transport in human erythrocytes. AB - We examined whether swelling-activated K-Cl cotransport is electrogenic in human erythrocytes. Baseline membrane potential, measured by the change in fluorescence of the carbocyanine dye diS-C3-5, was not different in hypotonically swollen ( 7.6 mV) or isosmotically swollen cells (-9.5 mV). We used hemisodium, a new highly selective Na ionophore, in varying concentrations, in the presence of a fixed outwardly directed Na gradient (intracellular Na, 75 mM; external Na, 1 mM) to vary membrane potential over a wide range despite identical K and Cl concentrations. The membrane potential varied between -8 and -90 mV. K influx increased slightly with hyperpolarization in swollen and nonswollen cells. However, the difference between the two fluxes, swelling-activated K influx, a measure of K-Cl cotransport, was unaffected by voltage changes, as was swelling activated K efflux. We conclude that K-Cl cotransport in human erythrocytes is electroneutral and by inference has a 1:1 stoichiometry. PMID- 8447369 TI - ANG II- or AVP-induced increases in protein synthesis are not dependent on autocrine secretion of PDGF-AA. AB - Previous studies have demonstrated that angiotensin II (ANG II) and arginine vasopressin (AVP) stimulate increased protein synthesis and cellular hypertrophy in cultured rat aortic smooth muscle cells (SMC). The aim of this study was to explore the hypothesis that ANG II- and/or AVP-induced increases in protein synthesis are mediated by autocrine secretion of platelet-derived growth factor (PDGF)-AA. Results demonstrated that ANG II or AVP increased expression of PDGF A, but not -B, chain mRNA. Additionally, conditioned media from ANG II- and AVP treated SMC had increased mitogenic activity for Swiss 3T3 cells, which could be inhibited with a neutralizing antibody to PDGF-AA. However, PDGF-AA-neutralizing antibodies did not inhibit ANG II- or AVP-induced increases in protein synthesis, and exogenous PDGF-AA did not stimulate increased protein synthesis. Furthermore, no PDGF-alpha receptors were evident based on 125I-labeled PDGF-AA binding studies. In summary, results indicate that ANG II- or AVP-induced increases in protein synthesis were not dependent on autocrine secretion of PDGF-AA. PMID- 8447370 TI - Enhanced keratinocyte prostaglandin synthesis after UV injury is due to increased phospholipase activity. AB - The possibility that increased eicosanoid synthesis in skin after ultraviolet light irradiation is due to enhanced phospholipase activity was examined. [3H]arachidonic acid-labeled human keratinocyte cultures exposed to 30 mJ/cm2 ultraviolet (UV) B were studied 6 h after injury. Bradykinin-stimulated release of [3H]arachidonic acid was increased 1.8-fold over release from control cultures by prior irradiation. In unlabeled cultures, prior irradiation produced a threefold increase in bradykinin-stimulated prostaglandin (PG) E2 synthesis as measured by immunoassay. The relative contribution of increased phospholipase vs. cyclooxygenase activity was therefore examined using stable isotope mass measurements of PGE2. By this method, prior irradiation increased bradykinin stimulated phospholipase activity 3.5-fold, while no change in total cellular cyclooxygenase activity was observed. The effects of irradiation on phospholipase activity were then assessed in more detail. The activities of phospholipase A2, arachidonoyl-CoA synthetase, and arachidonoyl-CoA lysophosphatide acyltransferase in cell homogenates were determined. No effect of UV exposure on the activity of these enzymes was observed. These results suggest that the increase in prostaglandin synthesis produced after UV irradiation is due to increased phospholipase activity, thus enhancing arachidonate release. PMID- 8447371 TI - Spatial arrangement and metabolic capacity of fiber types in self-reinnervated cat muscle. AB - The recovery potential of skeletal muscle was explored by examining cat muscle between 10 and 33 mo after complete transection and immediate surgical reunion of its own nerve. Biochemical analysis of single muscle fibers showed that the activities of key enzymes in energy metabolism (malate and lactate dehydrogenase and adenylokinase) were similar to normal for their respective fiber types, suggesting that incomplete recovery of the ability to sustain submaximal contraction in reinnervated muscles (T.C. Cope, C.B. Webb, and B.R. Botterman. J. Neurophysiol. 65: 648-656, 1991) is explained in some other way. Two independent statistical procedures for assessing the randomness of adjacencies of histochemically identified fiber types showed type grouping in some areas, but there were also many regions with randomly distributed fiber types. These findings demonstrate the potential for substantial recovery of both energy metabolism and dispersion of fiber types after self-reinnervation. PMID- 8447372 TI - Calcitonin gene-related peptide stimulates active Na(+)-K+ transport in rat soleus muscle. AB - Calcitonin gene-related peptide (CGRP) is found in a wide variety of tissues, including sensory and motor nerve endings in skeletal muscle. After intense electrical stimulation or K(+)-induced depolarization, CGRP can be released from nerve terminals and bound to receptors on sarcolemma. We show here that CGRP (rat and human) and salmon calcitonin stimulate 22Na extrusion and the influx of 86Rb and 42K in isolated rat soleus muscle. This leads to a pronounced (up to 56%) decrease in intracellular Na+, a minor increase in intracellular K+, and hyperpolarization. All these effects were blocked by ouabain or cooling, indicating that they reflect an acute stimulation of active electrogenic Na(+)-K+ transport. Capsaicin, which induces release of CGRP from sensory nerve endings, was found to exert similar effects on Na(+)-K+ transport. Various Na(+)-K+ pump stimulating agents have been shown to counteract the inhibitory effect of a high extracellular concentration of K+ ([K+]o) on muscle contractility (4, 20). CGRP and capsaicin were likewise found to improve contractile performance of muscles inhibited by high [K+]o, and these effects were blocked by ouabain. CGRP might play a role in the maintenance of Na(+)-K+ gradients and excitability during intensive muscle work, known to be associated with an acute rise in the interstitial K+ concentration. PMID- 8447373 TI - Mechanisms of adaptation of glucose transporters to changes in the oxidative chain of muscle and fat cells. AB - Cells in which glucose uptake is rate limiting respond to hypoxic insults with an increase in glucose transport activity. To understand the underlying cellular mechanisms involved in this adaptive response, the effects of an uncoupler of oxidative phosphorylation, 2,4-dinitrophenol (DNP), and of an inhibitor of the electron transport chain, rotenone, were compared with the effect of hypoxia in L6 muscle cells and 3T3-L1 adipocytes. All three conditions (DNP, rotenone, and 3% oxygen) elevated hexose uptake by approximately twofold in 4 h relative to control cells. All three insults decreased cellular ATP levels rapidly. A subsequent recovery was observed within 1-2 h in the presence of DNP or 3% oxygen, probably as a result of anaerobic production of ATP through increased glucose uptake and glycolysis. DNP and rotenone elevated the content of GLUT-1 protein in isolated plasma membranes and decreased it in intracellular light microsomes, suggestive of translocation of this transporter isoform. No change in GLUT-4 protein distribution was detected. In contrast, 3% oxygen caused a marked specific increase in GLUT-1 protein in both plasma membranes and microsomes. Consistently, cycloheximide had no effect on the hexose transport responses to DNP or rotenone, but prevented the response to hypoxia. However, GLUT-1 mRNA and the total cell content of GLUT-1 protein were elevated by all three treatments. It is proposed that within the time frame studied, reductions in the energy charge may activate the glucose transport system in L6 myotubes and 3T3-L1 adipocytes by GLUT-1 protein biosynthesis and translocation. When both responses exist, the biosynthetic pathway is dispensable, and posttranslational mechanisms, including transporter translocation suffice to sustain the adaptive elevation in glucose transport activity for several hours. PMID- 8447374 TI - High sensitivity of hypertensive aortic myocytes to norepinephrine and angiotensin. AB - Single-mass primary cultures were used for as long as 5 wk as the source of subcultured vascular smooth muscle cells for the study of their change of shape on the addition of agonists. We have compared the responses to angiotensin II, vasopressin, norepinephrine, and serotonin of myocytes derived from three different areas or the thoracic aorta (aortic arch and midthoracic and diaphragm areas) of adult Wistar-Kyoto normotensive rats (WKY) and spontaneously hypertensive rats (SHR). Once in secondary culture, vascular myocytes displayed different mean sizes according to their origin along the organ, as previously described in freshly dispersed aortic myocyte suspensions. Responses of the cells from the area of the aortic arch of both strains had the maximal amplitude to all agonists. Angiotensin and norepinephrine were more potent on myocytes derived from the three areas in SHR than in WKY. As this hypersensitivity persisted even after 5 wk in culture, it is believed to be pressure independent and thus might have a genetic rather than an adaptive origin. PMID- 8447375 TI - Involvement of arachidonic acid in the chloride secretory response of intestinal epithelial cells. AB - The inflammatory mediator, adenosine, induces chloride secretion from the human colonic epithelial cell line, T84, in a manner apparently independent of increases in adenosine 3',5'-cyclic monophosphate, guanosine 3',5'-cyclic monophosphate, or cytoplasmic Ca2+. This prompted a search for other messengers that might account for the secretory response. A possible role for arachidonic acid or a metabolite in the response to adenosine has been demonstrated 1) by showing a relationship between arachidonic acid mobilization and chloride secretion induced by the adenosine agonist 5'-(N-ethylcarboxamido)adenosine (NECA) and 2) by determining that exogenous arachidonic acid affects T84 cell function. Addition of NECA to T84 cells induces chloride secretion and release of radioactivity from cells preloaded with [3H]arachidonic acid with similar dose dependencies. The effect of NECA on chloride secretion is inhibited by the phospholipase A2 inhibitor 4-bromophenacyl bromide or the diglyceride lipase inhibitor RG80267 but is unaffected by inhibitors of lipoxygenase or cyclooxygenase. Arachidonic acid has a small but significant effect on chloride secretion when added alone to T84 cells and synergistically enhances, as does NECA, responses to calcium-dependent secretogogues. Thus receptor-stimulated release of arachidonic acid in T84 cells may provide a second-messenger system promoting chloride secretion, in addition to calcium and cyclic nucleotides. PMID- 8447376 TI - Inhibition of renal ornithine decarboxylase activity prevents kidney hypertrophy in experimental diabetes. AB - The selective ornithine decarboxylase (ODC) inhibitor difluoromethyl ornithine (DFMO) was used to investigate the role of polyamines in initial diabetic renal enlargement. ODC activity in kidneys from diabetic animals was increased (fivefold) 24 h after diabetes induction (P < 0.05), and throughout the study (7 days) the activity remained 2- to 3-fold elevated (P < 0.05). Insulin treatment normalized renal ODC activity, whereas DFMO treatment totally inhibited the kidney ODC activity. The kidney weight in diabetic rats was 21% higher than that of control rats (1,074 +/- 35 mg and 889 +/- 16 mg, P < 0.001). Insulin treatment normalized kidney weight (847 +/- 13 mg). Despite unaltered diabetic metabolic aberrations the kidney weight in DFMO-treated diabetic rats was normalized (911 +/- 7 mg). In conclusion, the ODC activity in diabetic kidneys undergoing hypertrophy was increased. Insulin treatment normalized both kidney weight and kidney ODC activity. Finally, selective inhibition of ODC activity by DFMO resulted in kidneys of normal size, despite unaltered diabetic metabolic aberrations. These findings support the hypothesis that polyamines play an important role in initial diabetic renal enlargement. PMID- 8447377 TI - Electrical resistance method for measuring volume changes in monolayer cultures applied to primary astrocyte cultures. AB - An electrical resistance method was developed to measure volume changes in substratum-attached monolayer cultures. Astrocytes in primary monolayer cultures prepared from neonatal rat cerebral cortex were placed in a confined channel containing a balanced salt solution, and the electrical resistance of the channel was measured using an applied alternating current. If the volume of the cells increases, then the volume of the solution within the channel available for current flow decreases by the same amount, resulting in an increase in the measured resistance through the channel. If the volume of the cells decreases, a decrease in resistance would be recorded. This method allows continuous measurements of volume changes in real time. When primary astrocyte monolayers were exposed to hyposmotic solutions (93-193 mosmol/kgH2O), they showed a rapid initial swelling and, in the continued presence of hyposmotic media, a characteristic regulatory volume decrease (RVD) in which there was a return to normal cell volume within approximately 20 min. Astrocytes exposed to hyperosmotic media (343-493 mosmol/kgH2O) gave a decrease in electrical resistance, indicating shrinkage. Putative endogenous effectors of astrocytic swelling, such as high extracellular K+ and glutamate, resulted in a much slower onset of swelling and no sign of RVD. This system can reliably measure the average change in cell monolayer volume to 1-2% and thus provides a sensitive means of continuous measurements of changes in cell volume in monolayer cultures. PMID- 8447378 TI - ETB receptors on aortic smooth muscle cells of spontaneously hypertensive rats. AB - The effect of the agonist sarafotoxin 6c (S6c), selective for endothelin (ET) receptor subtype B (ETB), on cytosolic free Ca2+ concentrations ([Ca2+]i) was determined by fura-2 methodology using aortic smooth muscle cells (ASMC) isolated from spontaneously hypertensive rats (SHR) and two normotensive strains, Wistar Kyoto (WKY) and Sprague-Dawley (SD) rats. The basal [Ca2+]i was significantly higher in the ASMC of SHR (139 +/- 8 nM) than WKY (107 +/- 7 nM) and SD (102 +/- 4 nM) rats. S6c produced concentration-dependent elevations in [Ca2+]i in the ASMC of WKY and SHR, whereas it did not evoke significant increases in the [Ca2+]i levels in the ASMC of SD rats. The peak [Ca2+]i levels observed with maximal concentrations of S6c (500 nM) was higher (P < 0.01) in the SHR (346 +/- 36 nM) than the WKY group (148 +/- 19 nM). The natural nonselective agonist, ET 1, evoked maximal [Ca2+]i in the ASMC of SHR, WKY, and SD rats of 635 +/- 43, 304 +/- 19, and 289 +/- 24 nM, respectively. Depletion of extracellular Ca2+ concentration led to the reduction of the peak [Ca2+]i response to ET-1 by 60 and 40% in the WKY and SHR cells, respectively, whereas the response to S6c remained unaffected. The ETA-selective antagonist, BQ-123 (1 microM), did not affect the [Ca2+]i response to S6c, whereas it attenuated the response to ET-1 by 90 and 70% in the WKY and SHR cells, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447379 TI - Glucose counterregulation: prevention and correction of hypoglycemia in humans. AB - The prevention or correction of hypoglycemia in humans is the result of both dissipation of insulin and activation of glucose counterregulatory (glucose raising) systems. Whereas insulin is the dominant glucose-lowering factor, there are redundant glucose counterregulatory factors. Furthermore, there is a hierarchy among the glucoregulatory factors. The first defense against a decrement in plasma glucose is decreased insulin secretion; this occurs with glucose decrements within the physiological range at a glycemic threshold of 4.6 +/- 0.2 mmol/l. However, biological glucose recovery from hypoglycemia can occur despite mild (approximately 2-fold) peripheral hyperinsulinemia and can occur in the absence of portal hypoinsulinemia. Thus additional (glucose counterregulatory) factors must be involved. Critical glucose counterregulatory systems are activated at glycemic thresholds of approximately 3.8 mmol/l (the level at which brain glucose uptake is first measurably reduced), well above the thresholds for symptoms of hypoglycemia (approximately 3.0 mmol/l) and those for cognitive dysfunction resulting from neuroglycopenia (approximately 2.7 mmol/l). Among the glucose counterregulatory factors, glucagon plays a primary role. Indeed, it may be that hypoglycemia does not occur if the secretion and actions of both glucagon and insulin, among the glucoregulatory hormones, are normal. Epinephrine is not normally critical, but it becomes critical to glucose counterregulation when glucagon is deficient. Because hypoglycemia develops or progresses when both glucagon and epinephrine are deficient and insulin is present, these three hormones stand high in the hierarchy of redundant glucoregulatory factors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447380 TI - Lactate transport studied in sarcolemmal giant vesicles from rats: effect of training. AB - The effect of training on lactate transport capacity was studied in giant vesicles obtained with collagenase treatment of rat skeletal muscles. Marker enzyme analyses demonstrated that these vesicles are predominantly of sarcolemmal origin. Treadmill training induced significant adaptations in the capacity of rat skeletal muscles to transport lactate but swimming [low-intensity training, approximately 50% of maximal oxygen consumption (VO2 max)] did not. After 7 wk of moderate (90% of VO2max)- and high-intensity (112% of VO2max) interval treadmill training the carrier-mediated equilibrium exchange flux with 30 mM lactate was increased by 58 and 76%, respectively. During 5 wk of detraining the capacity to transport lactate decreased to near control level. It is concluded that physical training can increase the capacity to transport lactate in rat skeletal muscles and that the training intensity is of great importance. The adaptation appears to include both an increased number of transport proteins and a higher affinity of the individual transporters. PMID- 8447381 TI - Nerve function in experimental diabetes in rats: effects of electrical stimulation. AB - The effects of unilateral electrical stimulation of the peroneal sciatic nerve branch were studied in streptozocin-diabetic rats of 12-wk duration. Stimulation was carried out over 7 days (10 Hz, 8 h/day) with chronically implanted electrodes. Compared with controls, there was a 25% conduction velocity (CV) deficit for the peroneal nerve supplying tibialis anterior muscle in the unstimulated leg, which was corrected by stimulation. For tibial fibers supplying soleus muscle, a similar diabetic CV deficit (20%) was normalized by stimulation, although soleus axons were not directly activated. In saphenous nerve, which has a functionally separate vascular supply, peroneal stimulation was ineffective. In anesthetized diabetic rats, stimulation caused an 18% reduction in tibialis anterior CV after 4 h. However, serial measurements showed progressive normalization of CV over 4 days of stimulation. On termination, CV returned to diabetic levels over 36-60 h. Sciatic nerve showed a 70% increase in resistance to hypoxic conduction failure with diabetes, which was halved by chronic stimulation. Acute experiments demonstrated that peroneal stimulation increased sciatic vascular conductance by 60%. We conclude that stimulation causes activity related improvements in diabetic nerve blood flow and metabolism. PMID- 8447382 TI - Muscle glucose uptake during and after exercise is normal in insulin-resistant rats. AB - It is not generally known whether impaired stimulation of muscle glucose metabolism in insulin-resistant states is specific to insulin stimulation. Our aim was to examine whether glucose uptake responded normally to exercise and postexercise recovery in insulin-resistant high-fat-fed (HFF) rats. Three-week HFF or Chow-fed [control (Con)] adult rats were studied 5 days after cannulation. Before, during, or immediately after (recovery) 50 min of treadmill exercise, bolus 2-deoxy-[3H]glucose and [14C]glucose were administered to estimate muscle glucose uptake (R'g) and glycogen incorporation rates. Mean exercise and recovery plasma glucose levels were similar in HFF and Con rats. In hindlimb muscles sampled, exercise and recovery R'g were similar in HFF and Con (e.g., red quadriceps exercise 104 +/- 13 vs. 113 +/- 8, recovery 45.3 +/- 3.9 vs. 47.7 +/- 4.5 mumol.100 g-1.min-1, respectively). Moreover, muscle glucose transporter (GLUT-4) content was not reduced in HFF rats. Glycogen resynthesis accounted almost entirely for R'g during recovery and was equivalent between groups. We conclude that impaired muscle glucose uptake and glycogen synthesis in HFF rats are characteristic of insulin but not of exercise or postexercise stimulation. PMID- 8447383 TI - Twin study of the 24-h cortisol profile: evidence for genetic control of the human circadian clock. AB - To determine whether genetic factors control the expression of human circadian rhythmicity, we analyzed the 24-h profile of plasma cortisol in 11 monozygotic and 10 dizygotic pairs of normal male twins. Blood was sampled every 15 min, and sleep was monitored. Circadian rhythmicity was characterized by measures of amplitude, phase, and overall waveshape. Pulsatility was quantified by pulse frequency, pulse amplitude, and relative contribution of pulsatile vs. circadian variations. Data were analyzed by a procedure specifically developed for twin studies. Genetic control was demonstrated for the timing of the nocturnal nadir and for the proportion of overall temporal variability associated with pulsatility. Environmental effects were detected for the 24-h mean and the timing of the morning acrophase. The timing of the cortisol nadir is a robust marker of human circadian phase and is dependent, under entrained conditions, on the length of the endogenous period. Animal studies have shown that the endogenous period and the pattern of entrainment to exogenous 24-h periodicities are genetically controlled. Our results indicate that, despite the increased impact of social inputs, genetic factors also control human circadian rhythmicity. PMID- 8447384 TI - Effects of exercise and immobilization on bone formation and resorption in young rats. AB - The influence of physical activity on bone formation and resorption was studied in the following three groups of 6-wk-old female rats: 30 controls, 24 sciatic denervation immobilized, and 28 treadmill exercised. Bone formation and resorption were determined from 45Ca retention, 45Ca excretion, bone calcium content, bone volume, and resorbing surface and bone formation rate assessed by tetracycline labeling. 45Ca (30 microCi) was administered intravenously to each animal before study, and the excretion of isotope in the urine and feces was then determined during the 6-wk experimental period. Exercise resulted in an initial increase in total excretion of 45Ca (P < 0.01) followed by a drop to below control levels (P < 0.001). The femoral 45Ca retention and calcium content of the exercised group were higher than that of the control group at week 6. Periosteal bone formation rate in the tibia was enhanced during days 32-41 (P < 0.01). With immobilization, the weekly excretion of 45Ca was persistently higher (P < 0.01), and the femoral 45Ca retention (P < 0.05) and calcium content (P < 0.01) were lower than the control group. Periosteal and endosteal bone formation rates were lower than in the controls over the first 31 days. In conclusion, exercise in young growing rats is associated with an initial increase and then a decrease in bone resorption while active bone formation is sustained. Immobilization for 6 wk results in an increase in bone resorption and a rapid fall in bone formation. PMID- 8447385 TI - Increased proliferation of osteoblast precursor cells in estrogen-deficient rats. AB - We have evaluated the in vivo and in vitro changes in osteoblast characteristics induced by estrogen deficiency and 17 beta-estradiol (E2) treatment in ovariectomized (OVX) rats. Estrogen deficiency induced osteopenia and increased bone turnover, as evidenced by bone histomorphometry at 1, 3, and 6 mo postovariectomy. Bone surface osteoblastic cells (OB) isolated from tibias of OVX rats, OVX rats treated with E2 (10 micrograms/kg body wt), and sham rats showed no difference in alkaline phosphatase activity and osteocalcin production in vitro. In contrast the proliferation rate of OB cells was higher in OVX rats compared with sham rats at all time points post-surgery, as shown by [3H]thymidine incorporation and cell number. The proliferation rate of alkaline phosphatase-positive marrow cells was also higher in OVX rats compared with sham rats. E2 treatment of OVX rats corrected histologic indexes of bone resorption and formation and normalized OB cell proliferation. induced by estrogen deficiency in OVX rats is related to an increased proliferation of osteoblast precursor cells present in the marrow stroma and along the endosteal bone surface. PMID- 8447386 TI - Insulin resistance in polycystic ovary syndrome: decreased expression of GLUT-4 glucose transporters in adipocytes. AB - We have found that women with polycystic ovary syndrome (PCOS) have decreased sensitivity and responsiveness to insulin. The present study was performed to determine whether this impaired insulin responsiveness was associated with diminished GLUT-4 glucose transporter content in adipocytes. Insulin-stimulated glucose transport and GLUT-4 abundance were measured in abdominal adipocytes from obese (n = 9) and lean (n = 7) PCOS as well as obese (n = 8) and lean (n = 8) control women matched for age and weight. No woman had impaired glucose tolerance. The maximal insulin-stimulated increment in adipocyte glucose transport was independently decreased by obesity and by PCOS. As expected, GLUT-4 content in adipocyte membranes was decreased in obesity (by 40%, P < or = 0.01). GLUT-4 content was also significantly decreased in PCOS (by 36%, P < or = 0.01), independent of obesity. There was a highly significant correlation (R = 0.66, P < = 0.001) between GLUT-4 content and insulin-stimulated glucose transport in adipocytes from individual women across the study population. We conclude that the diminished adipocyte insulin responsiveness in PCOS is associated with decreased GLUT-4 abundance. This represents a newly recognized phenotypic feature of the insulin resistance of PCOS. Moreover, in human adipocytes, GLUT-4 abundance is highly correlated with insulin responsiveness. PMID- 8447387 TI - Effect of prolonged exercise on muscle citrate concentration before and after endurance training in men. AB - It has been hypothesized that endurance training reduces carbohydrate utilization during exercise via citrate-mediated inhibition of phosphofructokinase (PFK). To test this hypothesis, vastus lateralis muscle biopsy samples were obtained from eight men before and immediately (approximately 10 s) after 2 h of cycle ergometer exercise at 60% of pretraining peak O2 uptake, both before and after 12 wk of endurance exercise training (3 days/wk running, 3 days/wk interval cycling). Training increased muscle citrate synthase (CS) activity from 3.69 +/- 0.48 (SE) to 5.30 +/- 0.42 mol.h-1.kg protein-1 and decreased the mean respiratory exchange ratio during exercise from 0.92 +/- 0.01 to 0.88 +/- 0.01 (both P < 0.001). Muscle citrate concentration at the end of exercise correlated significantly with CS activity (r = 0.70; P < 0.005) and was slightly but not significantly higher after training (0.80 +/- 0.19 vs. 0.54 +/- 0.19 mmol/kg dry wt; P = 0.16). Muscle glucose 6-phosphate (G-6-P) concentration at the end of exercise, however, was 31% lower in the trained state (1.17 +/- 0.10 vs. 1.66 +/- 0.27 mmol/kg dry wt; P < 0.05), in keeping with a 36% decrease in the amount of muscle glycogen utilized (133 +/- 22 vs. 209 +/- 19 mmol.kg dry wt-1.2 h-1; P < 0.01). The lower G-6-P concentration after training suggests that the training induced reduction in carbohydrate utilization results from attenuation of flux before the PFK step in glycolysis and is not due to citrate-mediated inhibition of PFK. PMID- 8447388 TI - Ovine fetal placental lactate exchange and decarboxylation at midgestation. AB - In a study of the metabolic implications of the large placental-to-fetal mass ratio that characterizes early fetal development, fetal plasma lactate disposal rate and CO2 production from fetal plasma lactate by fetus and placenta were measured in six midgestation (71-80 days) pregnant sheep. A constant fetal intravenous infusion of L-[U-14C]lactate and 3H2O was given to establish fetal steady-state lactate specific activity and to measure uterine and umbilical blood flows. Fetal and placental weights were 158.6 +/- 19.7 and 441.9 +/- 32.7 g, respectively. There was a significant net lactate flux into the uterine circulation (31 +/- 4.3 mumol/min, P < 0.01) but no measurable umbilical uptake. Fetal plasma lactate disposal rate was 21.2 +/- 2.7 mumol/min, approximately one half of which represented fetal lactate flux into the placenta (9.9 +/- 1.9 mumol/min). The oxidation rate of tracer lactate carbon to 14CO2 by placenta plus fetus was 72.6 +/- 4.7% of the infused tracer and was fairly evenly distributed between the placenta and the fetus (42.4 +/- 3.9 vs. 30.3 +/- 2.2%). The midgestation placenta metabolizes and produces fetal plasma lactate at rapid and nearly equal rates. This contrasts with the late-gestation placenta, which makes a small contribution to fetal lactate disposal and is a major net source of fetal lactate. PMID- 8447389 TI - Similar effects of NPY on energy metabolism and on plasma insulin in adrenalectomized ob/ob and lean mice. AB - A single intracerebroventricular (icv) injection of dexamethasone (250 ng) lowers brown adipose tissue (BAT) thermogenesis and whole body metabolic rates and raises plasma insulin concentrations within 30 min in adrenalectomized ob/ob mice with minimal effects in adrenalectomized lean mice. The present study was conducted to determine if intracerebroventricular neuropeptide Y (NPY), a neuropeptide regulated in part by glucocorticoids, would mimic effects of dexamethasone in these mice. NPY lowered BAT metabolism and whole body oxygen consumption and raised plasma insulin concentrations within 30 min in adrenalectomized ob/ob mice similarly to dexamethasone; but, unlike dexamethasone, NPY was as effective in modulating these metabolic responses in adrenalectomized lean mice as in ob/ob mice. Further, intracerebroventricular NPY increased food intake equally in both ob/ob and lean mice, whereas dexamethasone did not alter food intake during the 30 min postinjection period. These data are consistent with the hypothesis that NPY mediates some of the effects of intracerebroventricular dexamethasone action in ob/ob mice and that the divergence between ob/ob and lean mice lies in glucocorticoid control of NPY release/synthesis rather than in NPY action mechanisms. PMID- 8447390 TI - Analytical problems in detecting rapid insulin secretory pulses in normal humans. AB - The present study was undertaken to define the optimal experimental and analytical conditions necessary to reproducibly detect, in the systemic blood, small-amplitude rapid oscillations (period 8-15 min) of insulin and C-peptide. Samples for insulin, C-peptide, and glucose were drawn at 2-min intervals for 2 h from six normal subjects during constant glucose infusion and from five of the same subjects under basal conditions. To reduce measurement error, insulin and C peptide levels were measured 16 times at each time point. Three algorithms for pulse analysis (ULTRA, Cluster, PulseFit) were used to identify significant pulses, whereas autocorrelation and spectral analysis were used to identify potential regular periodic components in the data. In three of the five subjects studied under basal conditions, regular rapid oscillations could be consistently detected by autocorrelation when the analysis was based on eight replicates but not on duplicate series. In the remaining two basal studies and in all studies during glucose infusion, the majority of profiles did not have a significant periodic component. However, formal pulse analysis demonstrated that the number of pulses was similar during glucose infusion and basal conditions. Reproducibility was enhanced by increasing the number of replicates used in the analysis. We conclude that in the analysis of small-amplitude rapid insulin and C peptide oscillations, the sensitivity and specificity of the analysis is likely to be enhanced by performing multiple estimations at each time point and by using a minimum of two contrasting analytical approaches for pulse detection, which incorporate a method evaluating periodicity in conjunction with a pulse detection program designed to evaluate each individual oscillation separately. PMID- 8447391 TI - Disposal and distribution of rT3 in humans: a new double-tracer kinetic study. AB - A satisfactory definition of reverse 3,3',5'-triiodothyronine (rT3) kinetics in humans cannot be obtained if the plasma disappearance curve of the injected labeled hormone is the only experimental data available; most of the kinetic parameters can only be bounded within ranges showing unacceptable variabilities. To gain additional experimental data a double-tracer approach is proposed. After simultaneous injection of [125I]rT3 and 131I the following three experimental curves were determined in plasma: 1) the disappearance of [125I]rT3, 2) the disappearance of 131I, and 3) the appearance of 125I generated in vivo from labeled rT3 degradation. Combined analysis of these three curves, based on a complex six-compartment model, was developed and applied to data obtained in a group of normal subjects. Through this new analysis, fractional disposal rates and fractional exchange rates between the plasma compartment and the periphery are uniquely determined. The main physiologically interesting information on the degradation of the hormone that emerges from these studies are 1) all degradative pathways of rT3 generate iodide, being in all cases the [125I]rT3 dose completely recovered as 125I in plasma; and 2) most rT3 is degraded (65-90%) in peripheral tissues rapidly exchanging with the plasma pool. The extended experimental base is not yet sufficient to compute unique values for production rate (PR) and body mass (Qt); the validity of estimates of PR and Qt is based on the assumption that injected [125I]rT3 is able to trace all rT3 peripherally produced (from thyroxine). The new approach yields ranges for PR and Qt (1.12-2.15 micrograms/h and 2.88-8.24 micrograms) much narrower than those computable from the [125I]rT3 disappearance curve only (1.12-5.07 micrograms/h for PR and 2.88-23.7 micrograms for Qt). PMID- 8447392 TI - Exogenous substrate uptake by fetal lambs during reduced glucose delivery. AB - Normally, metabolism of exogenous glucose accounts for one-half of the normal fetal metabolic rate. When fetal glucose delivery is restricted for 2 wk, endogenous production increases to maintain glucose use. Such increased glucose production must originate either from increased uptake of other exogenous substrates (lactate or amino acids) or from use of endogenous substrates (via glycogenolysis or gluconeogenesis). Our purpose was to find if exogenous fetal substrate uptake increased during decreased fetal glucose delivery. Catheters were placed in eight lamb fetuses under general maternal anesthesia, and the animals were allowed 6 days to recover. Umbilical venoarterial blood concentration differences of antipyrine (during fetal antipyrine infusion), glucose, lactate, amino nitrogen-containing substances, and oxygen were measured before and after fetal glucose delivery was diminished by 3 h of maternal insulin infusion (5-10 mU.kg-1.m-1). Fetal substrate uptakes and substrate/oxygen quotients (i.e., the proportion of oxidative metabolism supported by complete oxidation of each exogenous substrate) were calculated. No increase occurred in the uptake of other exogenous substrates during deficient glucose delivery. Because even complete oxidation of all exogenous substrates did not meet fetal oxidative requirements, the fetus must oxidize endogenous substrates. If such a pattern of substrate use were to continue, fetal growth retardation would result. PMID- 8447393 TI - Aminoacylation of initiator methionyl-tRNA(i) under conditions inhibitory to initiation of protein synthesis. AB - Inhibition of protein synthesis in perfused rat liver deprived of either methionine or tryptophan results from a defect in peptide-chain initiation. Similarly, the decreased rate of protein synthesis in liver from rats deprived of food for 24 h and in skeletal muscle after 2 days of diabetes results from a defect in initiation. In the present study, the tissue content of tRNA(iMet) and its level of aminoacylation were measured in these conditions to determine whether methionyl-tRNA(iMet) formation is a mechanism involved in the regulation of initiation. The extent of aminoacylation of tRNA(iMet) in livers perfused with supplemented medium or medium deficient in either methionine or tryptophan was 64 +/- 2, 61 +/- 3, and 66 +/- 2% of the total accepting activity, respectively. The total tissue content of tRNA(iMet), expressed as a percentage of total RNA, was 1.7 +/- 0.1, 1.6 +/- 0.1, and 1.6 +/- 0.1 for the three conditions, respectively. In livers from starved rats, the extent of aminoacylation of tRNA(iMet) was 80 +/ 7% and the total tissue content of tRNA(iMet) was 1.9 +/- 0.1% compared with control values of 82 +/- 6 and 2.0 +/- 0.1%, respectively. In skeletal muscle from diabetic rats, the extent of aminoacylation of tRNA(iMet) was 79 +/- 4% and the total tissue content of tRNA(iMet) was 2.0 +/- 0.3% compared with values of 79 +/- 5 and 2.0 +/- 0.2% for control animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447394 TI - Glucose transport and transporters in muscle giant vesicles: differential effects of insulin and contractions. AB - Collagenase treatment of skeletal muscle results in the formation of large spheres of membranes (3-30 microns diam). A procedure is described for purification and concentration of these giant membrane vesicles prepared from rat muscle. Morphological observations, marker enzyme analysis, and immunoblotting demonstrate that the vesicles are of plasma membrane origin and that sarcoplasmic reticulum, T-tubules, and mitochondrial inner membranes are absent from the preparation. Western blots demonstrate that the vesicles contain GLUT-4 glucose transporters, whereas GLUT-1 could not be detected. Vesicles prepared from control muscle display specific transport of D-glucose with a maximum velocity (Vmax) for glucose influx of approximately 2,500 pmol.mg plasma membrane protein 1.s-1 and an apparent Michaelis constant (Km) of 16 mM measured at zero-trans conditions at room temperature. Muscle contractions in vivo doubled the Vmax of vesicle glucose transport and membrane GLUT-4 content but did not change Km. In contrast, in vivo administration of insulin did not affect vesicle glucose transport or membrane GLUT-4 content. The combination of insulin and contractions caused similar changes as did contractions alone. It is concluded that the present vesicle population contains membrane components almost exclusively derived from the plasma membrane and contains very little if any GLUT-1 but substantial amounts of GLUT-4. Thus the preparation allows the study of transport kinetics of pure GLUT-4 transporters. The procedure for preparing vesicles probably results in activation of the glucose transport system similar to the activation by insulin but not by contractions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447395 TI - Intense exercise and food restriction cause similar hypothalamic neuropeptide Y increases in rats. AB - Neuropeptide Y (NPY) is a potent central appetite stimulant whose concentrations rise markedly in hypothalamic appetite-regulating regions in food-deprived rats. To determine whether increased energy expenditure also affects hypothalamic NPY, we studied the effects of intense physical exercise in rats (n = 10) running voluntarily on a large-diameter exercise wheel. Running was initiated by restricting food intake but stabilized at an average of 8 km/day when food intake was matched to that in 11 nonexercised, freely fed controls [23.9 +/- 1.9 (SE) g/day vs. 24.7 +/- 1.3 g/day; P > 0.5]. Running expended approximately 40% of daily energy intake, and weight gain was significantly inhibited. A separate group (n = 10) of nonexercised rats was food restricted (approximately 15 g/day) to match the weights of the exercised rats. The rats were killed after 40 days, when both experimental groups weighed 30% less than controls (P < 0.01). Hypothalamic NPY concentrations showed significant (P < 0.01) increases of 30-70% in specific regions (arcuate and dorsomedial nuclei and medial preoptic and lateral hypothalamic areas) in both the running and food-restricted groups, compared with controls. There were no significant differences between the two experimental groups in NPY concentrations in any hypothalamic region. These findings suggest that negative energy balance, whether caused by reduced energy intake or increased expenditure, increases hypothalamic NPYergic activity. As NPY acts on the hypothalamus to increase body weight, these data support the postulated homeostatic role of NPY in maintaining nutritional state. PMID- 8447396 TI - Bromocriptine redirects metabolism and prevents seasonal onset of obese hyperinsulinemic state in Syrian hamsters. AB - Bromocriptine redirects metabolism and prevents seasonal onset of the obese hyperinsulinemic state in Syrian hamsters. Metabolic and hormonal effects of bromocriptine were studied in seasonally obese female Syrian hamsters, Mesocricetus auratus. Daily injections of bromocriptine and vehicle (controls) were made at light onset (10:14-h light-dark cycle) for 10 wk. After 9 wk of treatment blood samples were taken every 4 h during a day for assays of hormones, glucose, triglyceride, and fatty acids, and after 10 wk of treatment, tests were carried out to measure insulin-stimulated glucose disposal during a hyperinsulinemic clamp, lipid mobilization (rate of glycerol appearance), protein turnover (lysine flux and deamination), and body composition (deuterium dilution). Bromocriptine reduced percent body fat by 53% and increased percent lean body mass by 8%. It also decreased triglyceride levels by 52% and plasma free fatty acid concentration during the dark-near light onset by 49% and glycerol appearance by 25%. Protein synthesis and catabolism were increased by 62 and 56%, respectively, and deamination of amino acid was decreased by 53% by bromocriptine. Bromocriptine reduced plasma concentration of insulin throughout the day, especially at light onset, by 78% without change in baseline glucose level and markedly decreased steady state plasma glucose (by 40%) during a continuous infusion of insulin and glucose. It also reduced the nocturnal plasma concentration of prolactin by 90%, cortisol by 70%, and thyroid hormones (thyroxine and triiodothyronine) by 50% and dramatically altered the circadian profiles of these hormones and insulin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447397 TI - Expression of GLUT-4 glucose transporter in unweighted soleus muscle of normal and STZ-induced diabetic rats. AB - Effects of 6 days of hindlimb suspension on expression of glucose transporters were studied in the skeletal muscle of nondiabetic and streptozotocin-induced diabetic rats. Although total membrane protein recovered from soleus muscles tended to decrease with suspension, GLUT-4 protein concentration (amount per gram membrane protein) was increased by 66 and 91% compared with weight-bearing control in nondiabetic and diabetic rats, respectively. Therefore, the amount of GLUT-4 protein in whole soleus muscle did not decrease with the hindlimb suspension in normal and diabetic rats. In contrast, hindlimb suspension decreased GLUT-4 mRNA amount in whole soleus muscle by 47 and 27% in nondiabetic and diabetic rats, respectively. Thus the GLUT-4 protein-to-GLUT-4 mRNA ratio was increased 2.1-fold in nondiabetic and 1.4-fold in diabetic rats. The extensor digitorum longus muscle, which generally shows little response to unweighting, exhibited no such changes. These results suggest that the amount of GLUT-4 glucose transporter in the unweighted soleus muscle was maintained via a translational and/or posttranslational mechanism in nondiabetic rats as well as in streptozotocin-induced diabetic rats under the condition of reduced weight bearing activity. PMID- 8447398 TI - Metabolic and hemodynamic effects of insulin on human hearts. AB - Myocardial muscle is considered to be a target tissue for insulin action, but direct measurements of insulin's effects on cardiac hemodynamics and intermediary metabolism in humans are scarce. We combined great cardiac vein (GCV)/arterial catheterization with the euglycemic insulin clamp technique and thermodilution in six healthy middle-aged (53 +/- 2 yr) volunteers. In the fasting state, the myocardium extracted free fatty acid (FFA), lactate, pyruvate, glycerol, and beta hydroxybutyrate (6.4 +/- 0.8, 6.2 +/- 1.0, 0.58 +/- 0.12, 0.44 +/- 0.15, and 11 +/- 2 mumol/min, respectively) and consumed 0.26 +/- 0.02 mmol/min oxygen. As fasting plasma insulin (73 +/- 6 pmol/l) was raised and clamped at 503 +/- 16 pmol/l for 100 min while maintaining euglycemia (approximately 5 mmol/l), arterial levels of lactate and pyruvate rose (by 121 and 159%, respectively), whereas FFA, glycerol, and beta-hydroxybutyrate fell (by 69, 48, and 85%, respectively, all P < 0.001). Correspondingly, net myocardial uptake of glucose, lactate, and pyruvate increased to 18.9 +/- 3.5, 32.0 +/- 2.3, and 2.7 +/- 0.5 mumol/min, respectively, whereas net extraction of circulating FFA, glycerol, and beta-hydroxybutyrate was abolished (all P < 0.001). The stimulation of lactate and pyruvate uptake was the result of both increased arterial supply and enhanced myocardial extraction ratio (from 19 +/- 3 to 51 +/- 6% for lactate, from 26 +/- 5 to 44 +/- 5% for pyruvate, P < 0.001 for both). This shift from fat to carbohydrate fuel usage occurred in the absence of changes in oxygen consumption, heart rate, GCV blood flow, aortic pressures, coronary vascular resistance, and left ventricular end-diastolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447399 TI - Regulation of intestinal epithelial proliferation: a few answers, many questions. AB - The epithelium of the gastrointestinal tract mucosa is a highly dynamic and diverse mixture of cell populations requiring exquisite integration of the processes of cellular proliferation, differentiation, and senescence. It is likely that the proliferative compartment of the intestinal epithelium encompasses a hierarchy of totipotent and pluripotent stem cells in a manner similar to that which generates diversity in hematopoietic cell populations. Identification and characterization of the stem cell and progenitor populations in the intestine has been limited by the absence of markers or culture systems to identify these cells. Regulation of the proliferative compartment may be accomplished through the combined integration of key peptide growth factors and constituents of the extracellular matrix. The relative contribution of the epithelial populations themselves and the contributions made by associated cell populations such as pericryptal fibroblasts remain unclear. Recent studies have suggested that the transforming growth factors-alpha and -beta, two structurally unrelated peptide growth factors, might serve to regulate the balanced proliferation and turnover of intestinal epithelial cells. The proproliferative effects of TGF-alpha may be counterbalanced by the proliferation-inhibiting TGF beta. Recent studies have demonstrated close interregulation of these peptides, which act through autocrine and paracrine mechanisms in model intestinal epithelial cell lines. PMID- 8447400 TI - Pathway of insulin in pancreatic tissue on its release by the B-cell. AB - Insulin was revealed in the extracellular space and blood capillaries of the rat pancreas by applying protein A-gold immunocytochemistry. On the discharge by the B-cell, insulin diffuses in the extracellular space and interacts with the plasma membrane of all pancreatic cells. For the B-cell, the interstitial microvillar plasma membrane domain was preferentially labeled compared with the flat domain. In contrast, the digitations and flat domains of the basal plasma membrane of the acinar cells were equally labeled. In the endothelium, the labeling was superior in fenestrated areas than in the high cytoplasmic ones, the fenestrae, the luminal and abluminal plasma membranes being labeled. In the cytoplasmic areas the plasmalemmal vesicles were significantly labeled; the intercellular junctions were not. These results indicate that upon binding to the membrane, the transfer of insulin across the capillaries occurs through both the fenestrations and the vesicular system. The labeling of insulin in the subendothelial space and blood capillaries decreased significantly from the insular to the peri-insular and further to the teleinsular regions, demonstrating that insulin levels, high in insular tissue, decrease very rapidly as insulin circulates through and out of the pancreas. The pancreatic cells are thus exposed to very high levels of insulin that vary according to the regions, probably contributing to the topographical partition of the acinar parenchyma into peri-insular and teleinsular tissues. PMID- 8447401 TI - Dual effects of cisapride on gastric emptying and antropyloroduodenal motility. AB - There is little information about the effects of cisapride on human antropyloroduodenal motility, despite its documented efficacy for increasing the rate of gastric emptying in patients with gastroparesis. Cisapride has been reported to have little effect on gastric emptying in normal subjects. Antral, pyloric, and duodenal pressures were recorded simultaneously with gastric emptying in 20 healthy volunteers. Thirty minutes after the solid component of the meal had started to empty from the stomach, each subject received either 10 mg cisapride i.v. (11 subjects) or intravenous saline (9 subjects). Intravenous saline had no effect on either motility or gastric emptying. In contrast, cisapride administration was associated with a dual effect on motility, with initial suppression of antral pressure waves (P < 0.05) followed by stimulation of associated antropyloroduodenal pressure waves (P < 0.01). Gastric emptying slowed in the first 30 min after cisapride (P < 0.05), and this was followed by more rapid gastric emptying (P < 0.01). The amount of the meal emptied in the 60 min after cisapride correlated with the number of associated antroduodenal pressure waves (r = 0.75, P < 0.001) but not with the number of antral waves (r = 0.42, NS). These results indicate that cisapride in a dose of 10 mg i.v. has dual effects on gastric emptying and gastric motility. The stimulation of associated antral pressure waves is a plausible mechanism for the efficacy of cisapride in the treatment of gastroparesis. PMID- 8447402 TI - Mucosal stimulation evokes vasodilation in submucosal arterioles by neuronal and nonneuronal mechanisms. AB - The effects of mechanical stimulation of intestinal mucosa on submucosal arterioles of guinea pig ileum were examined using video microscopy of in vitro preparations consisting of submucosal plexus with adjacently attached mucosa. Mucosal stimulation did not alter the diameter of relaxed vessels but dilated arterioles preconstricted with phenylephrine or the prostaglandin analogue U 46619. Tetrodotoxin (TTX) or muscarinic receptor antagonists inhibited the vasodilation evoked by mucosal stimulation in 60% of preparations examined from normal and extrinsically denervated animals. The TTX-sensitive vasodilation to mucosa stimulation was partially inhibited by the 5-hydroxytryptamine3 (5-HT3) receptor antagonist ICS 205930. The TTX-insensitive vasodilation was largely prevented when the histamine receptor antagonists cimetidine and pyrilamine and the prostaglandin synthesis inhibitor indomethacin were applied. This study has demonstrated a reflex vasodilation to mucosal stimulation in an isolated submucosal plexus preparation that involves both neuronal and nonneuronal pathways. The neuronal pathway converges on cholinergic vasodilator neurons in the submucosal ganglia. The nonneuronal pathway involves the release of 5-HT, histamine, and prostaglandins from mucosal elements; 5-HT excites cholinergic vasodilator neurons, whereas histamine and prostaglandins dilate submucosal arterioles directly. PMID- 8447403 TI - Swallowing and upper esophageal sphincter contraction with transcranial magnetic induced electrical stimulation. AB - This study in three dogs explores the effect of magnetically induced electrical stimulation of the brain to induce swallowing and produce contraction of the upper esophageal sphincter (UES). Single stimuli were delivered at intervals from 15 s to 3 min. Studies were performed with and without perfusion of fluid into the pharynx and upper esophagus. Results showed that magnetic stimulation produced a twitch contraction of the UES when stimulus intensity was above a threshold that varied between 14 and 20% of the stimulator output. Increasing stimulus intensity progressively increased twitch amplitude. Magnetic stimulation also induced swallowing, above a stimulus threshold similar to that for induction of the UES twitch contraction. Fluid perfusion augmented the ability of the magnetic stimulus to induce swallowing. We concluded that a magnetically induced single electrical stimulus of the cerebral cortex produces UES contraction and induces swallowing. The effect on swallowing is facilitated by sensory stimulation of the pharynx. This technique holds the potential for further study of 1) motor and sensory neural mechanisms involved in the control of swallowing and 2) the assessment and management of oropharyngeal dysphagia in humans. PMID- 8447404 TI - Electroneutral uptake and electrogenic secretion of a fluorescent bile salt by rat hepatocyte couplets. AB - The role of membrane voltage as a driving force for the hepatic uptake and secretion of fluorescent bile salts has been examined in isolated hepatocyte couplets. The present study demonstrates that the fluorescent bile salt derivative (N-[7-(nitrobenz-2-oxa- 1,3-diazol-4-yl)]-7-amino-3 alpha, 12 alpha dihydroxy-5-cholan-24-oyl)-2-aminoethanesulfonate (7 beta-NBD-NCT) is taken up into hepatocytes by a saturable process with a Kt of 2.7 microM. Uptake rate was reduced by only 22% after total Na+ replacement and was independent of transmembrane potential difference over a range of -135 to +25 mV. In contrast, secretion into the canalicular space was strongly dependent on membrane voltage over the range from -34 to 0 mV in a manner consistent with electrodiffusion of an anion. Fitting the secretion time course to that predicted by electrodiffusion demonstrated that only approximately 50% of total secretion can result from electrodiffusion. Studies in isolated perfused liver confirmed this observation that depolarization caused a decrease in bile salt secretion rate. These results demonstrate that 7 beta-NBD-NCT is transported by a neutral uptake process at the sinusoidal membrane and is secreted across the canalicular membrane in part by electrogenic transport. This suggests that voltage changes could be a common pathway resulting in impaired organic anion secretion in diverse cholestatic syndromes. PMID- 8447405 TI - Vagal regulation of gastric prostaglandin E2 release by central TRH in rats. AB - The central action of the stable thyrotropin-releasing hormone (TRH) analogue, RX 77368, to induce vagal release of gastric prostaglandin E2 (PGE2) was investigated in urethan-anesthetized rats. Intracisternal RX 77368 (1.5-1,000 ng) dose dependently increased gastric PGE2 levels measured for 3 h in the perfusate of dialysis fibers implanted into the corpus submucosa. RX 77368 injected intravenously (1,000 ng) had no effect. The stimulatory action of RX 77368 (1.5 ng) on gastric PGE2 release was blocked by indomethacin and bilateral cervical vagotomy. Omeprazole did not alter the PGE2 response to 3 ng of RX 77368 and reduced by 39% PGE2 release induced by the 1,000-ng dose. RX 77368 (1.5 ng) by itself did not influence acid secretion but increased acid output to 117 +/- 18 mumol/2 h in indomethacin-pretreated rats. Indomethacin also increased by 97% the acid response to the 3-ng dose of RX 77368, but the effect of a maximal effective dose of RX 77368 was not modified. These results indicate that RX 77368 acts in the brain to induce a vagal-dependent stimulation of gastric PGE2 secretion which is biologically active to reduce the acid response to submaximal doses of TRH analogue. These data suggest a possible role of medullary TRH in the central vagal regulation of gastric PGE2 release. PMID- 8447406 TI - Regulation of exocrine pancreatic secretion by cerebral TRH and CGRP: role of VIP, muscarinic, and adrenergic pathways. AB - The central nervous system effects of thyrotropin-releasing hormone (TRH) and calcitonin gene-related peptide (CGRP) on exocrine pancreatic secretion were studied in freely moving rats. TRH (0.05-0.5 nmol) significantly stimulated, whereas CGRP (0.1-1.0 nmol) significantly inhibited, volume, protein, and bicarbonate secretion. Pretreatment of the animals with the ganglionic blocking agent chlorisondamine abolished the pancreatic responses produced by both peptides. In contrast, vagotomy abolished the stimulatory effect of TRH, whereas noradrenergic blockade with bretylium or phentolamine abolished the inhibitory effect of CGRP. Atropine significantly attenuated, but the vasoactive intestinal peptide (VIP) antagonist [D-p-Cl-Phe6, Leu17]VIP completely abolished the stimulatory effect of TRH. Pancreatic secretory responses stimulated by cerebral TRH or by peripheral VIP were inhibited dose dependently by peripheral [D-p-Cl Phe6,Leu17]VIP. Inhibition of pancreatic secretion induced by cerebral CGRP or by peripheral norepinephrine was prevented by intravenous phentolamine. These results indicate 1) cerebral TRH stimulates and cerebral CGRP inhibits exocrine pancreatic secretion in freely moving rats; 2) the effects of TRH are mediated by vagal efferents, and the primary peripheral transmitter appears to be VIP acting on VIP receptors, whereas muscarinic efferents are less important; and 3) the effects of CGRP are mediated by sympathetic noradrenergic efferents via alpha adrenergic receptors. PMID- 8447408 TI - Regulation of gastroduodenal emptying of solids by gastropyloroduodenal contractions. AB - We investigated the mechanisms of regulation of gastroduodenal emptying of solid meals by gastropyloroduodenal contractions in six conscious dogs. The spatial and temporal parameters of gastropyloroduodenal contractions were correlated with the rate of gastroduodenal emptying. The rate of gastroduodenal emptying exhibited a significant positive correlation with the 1) mean frequency of corporeal and antral contractions; 2) mean frequency, amplitude, duration, and area under pyloric contractions; 3) percentage of contractions that propagated in the distal duodenum, and the mean distance of their propagation; 4) percentage of contractions that propagated within the stomach, including the pylorus; 5) percentage of contractions that propagated from the antrum or the pylorus to the proximal duodenum; and 6) ratio of the mean frequency of contractions in the antrum to that in the proximal or the distal duodenum during the entire period of gastroduodenal emptying. The major factors that exhibited a significant negative correlation with gastroduodenal emptying were the total number, amplitude, duration, and area under contractions in the whole duodenum during the entire period of gastroduodenal emptying. We conclude that the antropyloroduodenal contractions, acting as a peristaltic pump, are a major factor in the regulation of gastric emptying of solid meals. The propagating contractions in the distal duodenum promote gastric emptying by rapidly removing the chyme from this area, whereas the nonpropagated contractions in the duodenum may provide a mechanical resistance to gastric emptying. PMID- 8447407 TI - Ursodeoxycholate mobilizes intracellular Ca2+ and activates phosphorylase a in isolated hepatocytes. AB - In isolated hamster hepatocytes, ursodeoxycholic acid (UDCA) mobilized intracellular free calcium ([Ca2+]i) and activated phosphorylase a with a half maximally effective concentration of 188 and 9 microM, respectively. Addition of ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) did not affect the maximum [Ca2+]i mobilized by UDCA; however, [Ca2+]i returned to basal levels in 4-5 min compared with > 10 min in the absence of EGTA. Both UDCA and vasopressin activated phosphorylase a to the same extent in the presence and absence of extracellular Ca2+, and the effect of both agents was abolished when the cells were depleted in Ca2+. Vasopressin (100 nM) did not further mobilize [Ca2+]i or activate phosphorylase a when combined with 500 microM UDCA. However, unlike vasopressin, UDCA did not stimulate inositol 1,4,5-trisphosphate (IP3) formation. In contrast to taurine-conjugated UDCA (TUDCA), concentration < or = 500 microM of glycine-conjugated UDCA (GUDCA) did not affect either [Ca2+]i or phosphorylase a. Lithocholic acid and taurolithocholic acid (TLCA) displayed the highest affinity for Ca2+. In addition, TLCA, chenodeoxycholic acid, and NaF stimulated Ca2+ efflux at concentrations as low as 100 microM, 200 microM, and 5 mM, respectively. Conversely, UDCA, TUDCA, and GUDCA presented the lowest affinity for Ca2+ and had no effect on Ca2+ efflux. The 28% increase in Ca2+ release induced by TLCA alone was further augmented to approximately 60% when TLCA was combined with UDCA, TUDCA, or GUDCA. However, Ca2+ efflux induced by NaF was not further increased by UDCA and its conjugates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447409 TI - Role of nitric oxide in gastric hyperemia induced by central vagal stimulation. AB - The effects of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, on the vagal cholinergic increase in gastric mucosal blood flow (GMBF) and acid secretion induced by intracisternal injection of the thyrotropin-releasing hormone (TRH) analogue, RX 77368, were studied. GMBF and acid secretion were measured simultaneously by the hydrogen gas clearance technique and titration of gastric perfusate in urethan-anesthetized rats. RX 77368 (30 ng) injected intracisternally stimulated gastric acid secretion and GMBF for 90 and 180 min respectively. GMBF was increased from basal 63 +/- 4 to 166 +/- 14 ml.min-1.100 g-1 at 60 min postinjection. L-NAME (3 mg/kg) injected intravenously 15 min before RX 77368 completely prevented the increase in GMBF induced by the TRH analogue, whereas the acid response was not modified. The effect of L-NAME was reversed by L-arginine but not by the stereoisomer D arginine. These results show that the increase in GMBF, but not the stimulation of acid secretion, induced by central vagal activation is mediated through a product of L-arginine-NO pathway. PMID- 8447410 TI - Site density of mouse intestinal glucose transporters declines with age. AB - To evaluate the effect of age on nutrient transport, the absorption rates of D glucose, D-fructose, L-alanine, L-aspartate, L-leucine, L-lysine, L-proline, folic acid, and nicotinamide were determined in isolated jejunal tissues of young (6.7 mo old) and aged (23.7 and 27.0 mo old) mice (COBS:SFW). D-Glucose and D fructose uptakes per milligram tissue were approximately 20-120% higher in the proximal jejunum and 15-50% higher in the distal jejunum of young mice. Amino acid and vitamin uptakes per milligram were also higher in young mice, but differences were not statistically significant. The number of Na(+)-D-glucose transporters per milligram tissue as estimated by specific phlorizin binding decreased with age. There was no age-related change in passive L-glucose permeability, in Kd of specific phlorizin binding, in transporter turnover rate, and in the molecular weight of the Na(+)-D-glucose transporter. Thus a reduction in D-glucose transporter site density fully accounts for the age-related decline in D-glucose transport rate per milligram small intestine. PMID- 8447411 TI - Role of carboxyl and sulfhydryl residues on rabbit small intestinal brush-border membrane Na(+)-glucose cotransporter. AB - The role of sulfhydryl (SH) and carboxylic acid residues in Na(+)-dependent glucose uptake, Na(+)-dependent phlorizin binding, and substrate exchange by the rabbit small intestinal brush-border membrane (BBM) Na(+)-glucose cotransporter was examined in sodium dodecyl sulfate-BBM vesicles. The sulfhydryl reagent p chloromercuribenzoate (PCMB) inhibited all three measures of cotransporter function in a dithiothreitol-sensitive manner with similar K0.5 values (concn of PCMB resulting in 50% inhibition). PCMB sulfonate had no effect on Na(+)-glucose cotransporter function < 250 microM. The carboxylic acid reagent 1-ethyl-3-(4 azonia-4,4-dimethylpentyl)carbodiimide no effect on Na(+)-glucose cotransporter function. N,N'-dicyclohexylcarbodiimide (DCCD) inhibited all three measures of cotransporter function with similar K0.5 values for inhibition. Inhibition by DCCD did not require addition of a nucleophile. In contrast, PCMB-pretreated cotransporter was insensitive to DCCD in the absence of added nucleophile with respect to substrate transport (Na(+)-dependent glucose uptake) but not Na(+) dependent phlorizin binding. These results indicate an intravesicular or lipophilic environment for both the PCMB-reactive SH residue and the DCCD reactive carboxylic acid residues, suggesting that a SH residue may act as an endogenous nucleophile for interaction of DCCD with the Na(+)-glucose cotransporter and suggesting that different carboxylic acid residues may be involved in Na(+)-dependent glucose uptake and Na(+)-dependent phlorizin binding. PMID- 8447412 TI - Molecular mechanism of two noncompetitive inhibitors of Na(+)-glucose cotransporter: comparison of DCCD and PCMB. AB - The effects of noncompetitive inhibitors of Na(+)-dependent glucose uptake, p chloromercuribenzoate N,N'-dicyclohexylcarbodiimide (DCCD), on substrate-induced cotransporter conformational changes were examined using fluorescein isothiocyanate (FITC) and tryptophan fluorescence. p-chloromercuribenzoate (PCMB) inhibited both substrate-induced conformational changes with similar concentration required for 50% quenching/enhancement of tryptophan or FITC fluorescence. In contrast, DCCD inhibited the Na(+)-induced conformational change with an apparent concentration resulting in 50% inhibition (K0.5) of 18 microM and the glucose-induced conformational change with an apparent K0.5 of 5 microM. DCCD slightly increased the apparent K0.5 for the Na+ concentration required for Na(+)-induced conformational change. DCCD and PCMB altered tryptophan accessibility to quench reagents in all three conformations. Tryptophan residues on the PCMB-treated cotransporter were more Cs+ than I- sensitive in contrast to the unlabeled cotransporter. The PCMB-treated cotransporter had a reduced response to Na+, suggesting that the mode of PCMB inactivation of cotransporter activity resulted from conformational changes in the substrate-free cotransporter. DCCD had a smaller effect on cotransporter tryptophan quench reagent susceptibility. However, DCCD-labeled cotransporter was equally accessible to I- and Cs+, and the DCCD-labeled cotransporter did not respond to substrates. Loss of charge distribution around cotransporter tryptophans correlated with loss of substrate-induced conformational changes. PMID- 8447413 TI - Ontogeny of sucrase-isomaltase gene expression in rat intestine: responsiveness to glucocorticoids. AB - The goal of our study was to determine how sucrase-isomaltase (SI) gene expression in the rat small intestine is modulated by glucocorticoids during the second and third postnatal weeks. SI mRNA was quantitated by Northern blot and was compared with sucrase activities in the same tissue samples. The role of endogenous glucocorticoids was assessed by measuring SI mRNA and enzyme activity in rat pups adrenalectomized (ADX) on postnatal day 9. ADX pups showed a retarded appearance of sucrase activity compared with sham-operated control pups, and the appearance of SI mRNA paralleled the enzyme activity. To determine the role of exogenous glucocorticoids, a saturating dose of dexamethasone (Dex) was administered daily in three series of experiments starting on days 10, 16, and 18. In the day 10 series, Dex caused precocious appearance of both SI mRNA and sucrase activity. In the day 16 series, Dex accelerated the rate of rise of the two parameters, whereas by day 18 there was no significant effect of Dex. To investigate whether the accelerated rise in the day 16 series was associated with changes in epithelial cell kinetics, the location of SI protein was assessed by immunofluorescence staining. The results indicated that the effect of Dex at this age was due to faster emergence of SI-bearing enterocytes from the intestinal crypts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447414 TI - Effect of epidermal growth factor on enterocyte brush-border surface area. AB - The effect of acute in vivo epidermal growth factor (EGF) exposure on intestinal absorptive surface area was examined in blind jejunal loops in New Zealand White rabbits (500-900 g). Brush-border surface area was assessed by electron microscopy at 30 and 120 min, and total surface area was assessed by the fluorophore 1-[4-(trimethylamino)phenyl)]-6-phenylhexatriene (TMA-DPH) at 10 and 60 min after EGF exposure. Mucosa obtained at 120 min was also used for morphometrics and analysis of membrane composition and fluidity. Brush-border surface area was significantly increased in EGF-treated tissue after 30 (42%) and 120 min (60%). Total absorptive surface area measured by TMA-DPH was increased more than twofold after 10 and 60 min EGF exposure. The increase in absorptive surface area was abolished by pretreatment with intravenous verapamil. Mucosal morphometrics and membrane sucrase activity, total phospholipids, cholesterol content, cholesterol-to-phospholipid ratio, phospholipid species (wt%), phospholipid fatty acid composition, and fluidity did not differ between control and EGF-treated tissue. These findings indicate that EGF can rapidly increase brush-border surface area by a mechanism that appears to be due to a redistribution of existing performed microvillus plasma membrane. PMID- 8447415 TI - Bile salts and ileal calcium transport in rats: a neglected factor in intestinal calcium absorption. AB - Ileum displays little active transcellular calcium (Ca2+) absorption but is credited with the bulk of Ca2+ absorbed in vivo. We examined the effect of taurodeoxycholic acid (TDC, 2 mM), a bile salt, on mannitol (MN, a marker of intercellular solute traffic) and Ca2+ fluxes in rat ileum. In the absence of electrochemical gradients between the mucosal (M) and serosal (S) bathing media in an Ussing chamber, net flux (Jnet) was observed in the S-to-M direction for both MN and Ca2+, i.e., the unidirectional secretory S-to-M flux (Js-->m) exceeded the absorptive M-to-S flux (Jm-->s). Mucosal TDC caused simultaneous increase in transepithelial conductance and Js-->m for both MN and Ca2+. This was followed by even greater increases in MN and Ca2+ Jm-->s, so that ultimately Jm- >s equaled Js-->m in each case. In control tissue, Js-->m for Ca2+ appeared to permeate exclusively through the intercellular MN pathway while part of Jm-->s for Ca2+ appeared to traverse through a non-MN route. After the TDC-induced increase in intercellular solute permeability, both Ca2+ fluxes appeared to traverse through the aqueous MN conduit. During the postprandial state, the presence of bile salts and the relative abundance of Ca2+ in ileal lumen can cause bulk Ca2+ absorption through the intercellular pathway. PMID- 8447416 TI - Stilbenes stimulate T84 Cl- secretion by elevating Ca2+. AB - Basolateral but not apical application of 10-200 microM 4,4' diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) or 4-acetamido-4' isothiocyanostilbene-2,2'-disulfonic acid (SITS) to T84 monolayers produced a transient increase in short-circuit current (Isc), followed by a sustained inhibition. 4,4'-Dinitrostilbene-2,2'-disulfonic acid (DNDS) had no effect. The increase in Isc produced by DIDS represents Cl- secretion and appears to result from Ca2+ elevation, because in all respects except time course the response to DIDS mimicked the response to the Ca(2+)-elevating agent thapsigargin. Fura-2 measurements established that thapsigargin elevates Ca2+ in T84 cells, but Ca2+ responses to DIDS could not be established directly because DIDS absorbs strongly at the critical wavelengths. Responses to DIDS and thapsigargin were 1) blocked by bumetanide; 2) not blocked by basolateral Ba2+; 3) completely nonadditive; 4) strongly synergistic with basal levels of Isc or with Isc increases produced by elevating adenosine 3',5'-cyclic monophosphate (cAMP; with forskolin) or guanosine 3',5'-cyclic monophosphate (with heat-stable enterotoxin); and 5) reversibly abolished by removal of basolateral Ca2+. Interactions between Ca2+ and cAMP-elevating agents strongly support a model of Cl- secretion in which apical Cl- conductance is activated by cyclic nucleotides but not by Ca2+ while basolateral K+ channels are activated by Ca2+. In contrast with this mechanism, whole cell patch-clamp recordings of nonconfluent T84 cells indicated that DIDS and other Ca(2+)-elevating agents stimulated an increase in Cl- conductance. Thus increases in cytosolic free Ca2+ in nonconfluent T84 cells activate conductances that differ from those in confluent monolayers. PMID- 8447418 TI - Intestinal distension alters vagal efferent activity and small intestinal transport in vivo. AB - We investigated whether intestinal distension altered net water absorption by an adjacent noncontiguous segment of intestine and the mechanism for this effect. Influx and efflux catheters were placed in two intestinal loops, after which the bowel was transected between the loops. During perfusion with Ringers-HCO3-, the proximal loop efflux catheter was elevated 5, 10, or 15 cm above the plane of the rat. Net water absorption was measured in the nondistended caudal (control) loop. Elevation of the proximal loop efflux catheter caused distension and increased intraluminal pressure in this loop but did not alter the circumference or intraluminal pressure of the caudal loop. Distension increased net water absorption by the caudal loop if the vagi were intact and the splanchnic nerves transected. Afferent vagotomy prevented the distension effect. Using the intracellular recording technique, we were able to show that the increase in absorption resulted from a reduction in the activity of vagal neurons innervating the gastrointestinal tract. Intestinal distension reduced the neural activity of 24 of 26 vagal efferent neurons. Our results demonstrate that after splanchnectomy intestinal distension activates a neural circuit that includes afferent and efferent vagal fibers, resulting in increased water absorption. PMID- 8447417 TI - Interplay of VIP and nitric oxide in regulation of the descending relaxation phase of peristalsis. AB - Involvement of vasoactive intestinal peptide (VIP) and nitric oxide (NO) in neurally induced relaxation was examined in smooth muscle from rat colon. Relaxation induced by field stimulation or radial stretch (i.e., descending relaxation phase of the peristaltic reflex) was accompanied by VIP release and NO production. NG-nitro-L-arginine (L-NNA) abolished NO production in both preparations but only partly inhibited VIP release (45 +/- 8% at 8 Hz and 59 +/- 10% at 10 g stretch) and relaxation (62 +/- 5% and 35 +/- 6%); the effect of L NNA was reversed by L-arginine but not D-arginine. The pattern implied that NO production normally acts to enhance VIP release. In addition, VIP induced relaxation and stimulated NO production in muscle strips and isolated colonic muscle cells: L-NNA abolished NO production but only partly inhibited relaxation (58 +/- 6%); oxyhemoglobin had no effect. The effect of L-NNA on relaxation was reversed by L-arginine but not by D-arginine. The protein kinase A inhibitor (R) p-adenosine 3',5'-cyclic phosphorothioate [(R)-p-cAMPS] and the protein kinase G inhibitor KT5823 inhibited VIP-induced relaxation by 76 +/- 5 and 35 +/- 4%, respectively; a combination of the two inhibitors abolished relaxation. (R)-p cAMPS blocked the direct relaxant effect of VIP, whereas KT5823 blocked the indirect effect of VIP mediated by NO.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447419 TI - Neural modulation of canine duodenal bile acid delivery in the interdigestive and postprandial periods. AB - The neural modulation of gallbladder filling-emptying and duodenal delivery of canine hepatic biliary output was studied in conscious dogs using transient cold blockade or transection of the cervical vagosympathetic nerves previously isolated in skin loops on either side of the neck. Gallbladder filling-emptying was defined as the algebraic difference between a steady-state rate of hepatic secretion [established by a continuous intravenous infusion of [14C]taurocholic acid (TCA)] and the duodenal rate of delivery of [14C]TCA (measured by duodenal marker perfusion). Duodenal motility was recorded manometrically. Experiments in the fasted and fed state were performed under control conditions, during cold blockade, and after transection of the cervical vagosympathetic nerves. Under control conditions: 1) during fasting, the majority of hepatic [14C]TCA output was stored in the gallbladder during the first half of the migrating myoelectric complex (MMC). An increased rate of duodenal delivery and partial gallbladder emptying occurred before phase III of the MMC. 2) Feeding induced an immediate increase in duodenal bile acid delivery and gallbladder emptying. After cold blockade or transection: 1) partial gallbladder emptying before phase III of the MMC was abolished. 2) The immediate postprandial increase in duodenal bile acid delivery and gallbladder emptying was abolished even when the animal received a continuous duodenal infusion of the duodenal aspirate of another fed animal (to control for the effect of impaired gastric emptying after cold blockade). In addition, cold blockade significantly reduced the effect of an exogenous infusion of cholecystokinin octapeptide on gallbladder emptying. These results suggest that neurons in the canine cervical vagosympathetic nerves play a major role in the regulation of rhythmic partial emptying of the gallbladder in the interdigestive period, coordinate a cephalic phase of postprandial gallbladder emptying, and are important in mediating the effects of cholecystokinin on the gallbladder during the gastric and enteric phases of postprandial gallbladder emptying. PMID- 8447420 TI - Polyamines are necessary for cell migration by a small intestinal crypt cell line. AB - Studies from our laboratory have shown that polyamines are essential for the normal repair of duodenal erosions induced in vivo in a rat stress-ulcer model. In that model, the inhibition of ornithine decarboxylase, a rate-limiting enzyme of polyamine biosynthesis, with alpha-difluoromethylornithine (DFMO) almost entirely prevented healing. Healing could be restored by oral polyamines. In this paper, we have investigated whether the polyamines are required for the early stages of epithelial restitution using an IEC-6 cell culture model of cell migration. Treatment of the cells with DFMO for 4 days reduced cell migration 80%. Migration could be restored to normal by concomitant treatment with putrescine (PUT), spermidine (SPD), or spermine (SPM), but not by their addition during the migration period (6 h) only. If DFMO treatment was not begun until the migration period, it still reduced cell migration 20%, and this deficit could not be restored by concomitant addition of the polyamines. Intracellular polyamine levels at these times, i.e., 6 h or 4 days, were an important factor in these results. Only PUT was undetectable after 6 h of DFMO. SPD and SPM were still at normal levels at 6 h. SPD was undetectable at 4 days, but SPM was still at 40% of normal. These data give added importance to PUT because its absence reduced cell migration after only 6 h, while SPD and SPM were still present in normal amounts. Perhaps exogenous SPD and SPM restored cell migration when present with DFMO for 4 days treatment primarily because they contributed to intracellular PUT through the acetyltransferases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447421 TI - Intracellular free Mg2+ with pH changes in cultured epithelial cells. AB - Intracellular pH (pHi) alters cytosolic concentrations of electrolytes, including Ca2+ and Na+. The present studies determined the effect of pHi on intracellular free Mg2+ activity in two epithelial cell lines: one possessing absorptive and secretory functions (Caco-2 intestinal cells) and the second, an absorptive kidney cell line derived from the opossum kidney (OK).pHi and spatial H+ distribution were assessed by 2',7'-bis(carboxyethyl)-5(6')-carboxyfluorescein after an NH4+ pulse to provide rapid changes in pHi. [Mg2+]i, [Ca2+]i, and [Na+]i were measured by fluorescence techniques. [Mg2+]i and spatial Mg2+ distribution within single cells were not changed with rapid alkalinization and acidification procedures in both intestinal and renal cell lines. Alkalinization results in significant increases in [Ca2+]i and [Na+]i that return to basal levels after acidification in both Caco-2 and OK cell lines. These studies indicate that [Mg2+]i is not altered with changes in pHi and suggest that [Mg2+]i is maintained by means not related to pHi in these epithelial cells. PMID- 8447422 TI - Paracrine control of gastric epithelial cell growth in culture by transforming growth factor-alpha. AB - Studying primary cultures of replicating canine oxyntic mucosal cells, we found evidence for modulation of cell growth by endogenous factors. [3H]thymidine incorporation into DNA was rapid with cells cultured in medium free of serum or added growth factors, and growth rates of these cultures were markedly dependent on plating density, indicating mitogenic control by soluble endogenous growth factors. Data indicated that endogenous transforming growth factor-alpha (TGF alpha) exerted mitogenic control under the following conditions. 1) TGF-alpha was detected in the cultured cells by radioimmunoassay and immunohistochemistry. 2) TGF-alpha-like immunoreactivity and receptor reactivity were present in the medium in concentrations sufficient to exert mitogenic control. 3) Receptors for TGF-alpha and epidermal growth factor (EGF) were present in the cultures. 4) Immunoabsorption by a TGF-alpha-specific antisera reduced [3H]thymidine incorporation. TGF-alpha was localized to parietal cells by immunohistochemistry and cell separation. In contrast, combined [3H]thymidine autoradiography and immunohistochemistry with anti-TGF-alpha did not detect TGF-alpha in dividing cells. We conclude that parietal cell TGF-alpha exerts paracrine control of mucosal cell growth in vitro, and we speculate that this is an important paracrine mechanism in vivo. PMID- 8447423 TI - Increased expression of PDGF A- and B-chain genes in rat lungs with hypoxic pulmonary hypertension. AB - To study the molecular basis of vascular remodeling in pulmonary hypertension, we developed an experimental system in which male Sprague-Dawley rats were exposed to hypoxia for up to 3 wk. Both the right ventricular systolic pressure and gravimetric index for right ventricular hypertrophy were higher in rats exposed to hypoxia for 3 wk than those of age-matched control rats (P < 0.01), indicating that pulmonary hypertension was established under conditions used. To examine the possible involvement of platelet-derived growth factor (PDGF) in the pulmonary vascular remodeling caused by hypoxia, we cloned rat PDGF A- and B-chain cDNA and prepared specific cRNA probes. Northern blot analysis revealed that PDGF B-chain mRNA levels in the lungs were increased, reached a maximum of day 1, and were sustained at day 3, whereas PDGF A-chain mRNA levels reached a maximum on day 3. Thus the increase in the PDGF B-chain mRNA level precedes that in the PDGF A chain mRNA level. These results suggest that the PDGF A- and B-chain products may be coordinately and sequentially involved in hypoxic pulmonary vascular remodeling. PMID- 8447424 TI - Ionic currents in rat pulmonary and mesenteric arterial myocytes in primary culture and subculture. AB - The electrophysiological properties of cultured single vascular smooth muscle (VSM) cells from rat pulmonary (PA) and mesenteric (MA) arteries were studied using the whole cell patch-clamp technique. Cells were studied at 3-7 days as primary cultures, or were replated after 10-20 days and subcultured for 2-5 days. In the standard physiological bath solution (containing 1.8 mM Ca2+), and with 125 mM K+ + 10 mM ethylene glycol-bis(beta-aminoethyl ether)- N,N,N',N' tetraacetic acid (EGTA)-filled pipettes, both PA and MA primary cultured cells had high input resistances (mean = 2-3 G omega) and resting membrane potentials of about -40 mV. The cells were clamped at a holding potential of -70 mV. Depolarization to -20 mV or more evoked a transient inward current (Iin) that was eliminated in Ca(2+)-free bath solution; this indicates that Iin was carried by Ca2+. Iin was substantially smaller in subcultured cells from both PA and MA. Depolarization also activated three components of outward current (Iout) in primary cultured PA and MA cells: a rapidly inactivating transient component (Irt), a slowly inactivating transient component (Ist), and a steady-state (noninactivating) component (Iss). All three components of Iout were inhibited to varying degrees by 5 mM 4-aminopyridine and were eliminated by replacing intracellular K+ with Cs+, but were only minimally affected by removal of extracellular Ca2+. These results suggest that this Iout was carried by K+ and was voltage gated. Little external Ca(2+)-dependent Iout was observed under these conditions, but a substantial Ca(2+)-dependent component was seen when the EGTA concentration in the pipettes was reduced to 0.1 mM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447425 TI - Hypoxia reduces potassium currents in cultured rat pulmonary but not mesenteric arterial myocytes. AB - To explore possible mechanisms underlying hypoxia-induced pulmonary vasoconstriction, the effect of hypoxia on outward K+ current (Iout) was evaluated in primary cultured rat pulmonary (PA) and mesenteric (MA) arterial smooth muscle cells using the whole cell patch-clamp technique. When the cells were bathed in standard physiological salt solution and the patch pipettes contained Ca(2+)-free media with 10 mM ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA), virtually all of the Iout, including both the rapidly inactivating component (Irt) and the steady-state (noninactivating) component (Iss), was mediated by voltage-gated K+ channels. Reduction of O2 tension in the bath solution from 155 Torr to < 74 Torr with sodium dithionite reversibly inhibited both Irt and Iss in PA myocytes, but not in MA myocytes. The hypoxia-sensitive Iss was activated at about -50 mV; thus, some of the channels responsible for this current may be open at the resting membrane potential (-40 +/- 1 mV) of PA cells used in this study. Hypoxia also significantly depolarized PA cells bathed in PSS (1.8 mM Ca2+) from -40.7 +/- 1.3 to -24.0 +/- 2.4 mV, and PA cells bathed in Ca(2+)-free PSS (0.1 mM EGTA) from -38.4 +/- 1.3 to -26.1 +/- 3.9 mV. The hypoxia-induced inhibition of Iout in PA cells was accompanied by an apparent increase in inward Ca2+ current.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447426 TI - Activation of phospholipase D in rat type II pneumocytes by ATP and other surfactant secretagogues. AB - Surfactant phospholipid secretion can be stimulated by a variety of agonists acting via a number of signal-transduction mechanisms. To determine whether phospholipase D has a role in surfactant secretion, we examined phosphatidylethanol formation in response to surfactant secretagogues in primary cultures of rat type II cells. Phosphatidylethanol formation was stimulated by ATP, 12-O-tetradecanoylphorbol-13 acetate (TPA), and dioctanoylglycerol, surfactant secretagogues that also activate protein kinase C. Surfactant secretagogues that act via other signaling mechanisms had no effect on phosphatidylethanol formation. The effect of ATP on phosphatidylethanol formation was dependent on time, with the maximum stimulation being achieved in approximately 10 min. It was also dependent on ATP concentration. The ATP concentration eliciting 50% of the maximum effect (EC50) was 2.45 x 10(-6) M. This was similar to the EC50 reported for ATP stimulation of surfactant secretion. ATP analogues also stimulated phosphatidylethanol formation with a potency order generally similar to that reported for surfactant secretion. The effects of ATP, TPA, and dioctanoylglycerol were antagonized by protein kinase C inhibitors. We speculate that activation of protein kinase C either directly by TPA and dioctanoylglycerol or indirectly subsequent to phosphoinositide-specific phospholipase C activation by ATP leads to initial stimulation of surfactant secretion as well as activation of phospholipase D. The action of phospholipase D on cellular phospholipids then leads to further generation of diacylglycerols, continued activation of protein kinase C, and sustained surfactant secretion. PMID- 8447427 TI - Type II pneumocyte hypertrophy without activation of surfactant biosynthesis after partial pneumonectomy. AB - Hypertrophic and normotrophic type II pneumocytes were isolated from pneumonectomized adult rats by unit gravity (1 g) sedimentation or by fluorescence-activated cell sorting (FACS). In vivo or in vitro, hypertrophic cells incorporated significantly more 5-bromo-2'-deoxyuridine or tritiated thymidine into acid-insoluble material than did normotrophic cells. By FACS analysis of cell subpopulations isolated by 1 g, > 97% of normotrophic cells had G0-phase DNA content. In contrast, the cell cycle distribution of hypertrophic cells was 75% G1, 5% S, and 20% G2/M phases. Rates of incorporation of tritiated choline into total cellular phosphatidylcholine (PC) were identical in type II cells isolated from normal or pneumonectomized rats. The intracellular contents of disaturated phosphatidylcholine (DSPC) and total PC, as well as the ratio of these two lipids, were the same in hypertrophic and normotrophic cells from pneumonectomized rats and in cells isolated from normal rats. No significant difference was observed in the rate at which hypertrophic or normotrophic cells incorporated choline into DSPC. These results demonstrate that type II pneumocyte hypertrophy after pneumonectomy reflects balanced cell growth secondary to cell cycle progression in vivo. The data also indicate that epithelial cell hypertrophy after pneumonectomy, in contrast to that which develops after more acute lung injury, occurs without activation of surfactant biosynthesis or storage. PMID- 8447428 TI - Inositol trisphosphate is involved in norepinephrine- but not in hypoxia-induced pulmonary arterial contraction. AB - The role that second messengers play in pulmonary vasoconstriction is not understood. The purpose of this study was to directly measure inositol phosphates in isolated pulmonary arterial preparations before and during norepinephrine (NE) stimulation and acute hypoxia. Rat main pulmonary arteries were isolated and incubated with myo-[3H]-inositol. After incubation, control tissue was stimulated with 0.5 microM NE or 30 mM KCl. Test preparations were precontracted with 30 mM KCl and then exposed to hypoxia. Samples were homogenized and applied to a high pressure liquid chromatography column for analysis of inositol phosphates. Results show that inositol trisphosphate (IP3) increases twofold at 5 s following NE stimulation. Thirty micromolars of KCl results in a slight but significant increase in IP3 formation at 5 min following the stimulation. Phentolamine inhibits the KCl-induced increase in IP3 formation, whereas A23187 has no effect on IP3 levels. Hypoxia caused a biphasic contraction in the precontracted isolated rat pulmonary artery. IP3 levels did not change during the hypoxic period. In conclusion, NE causes a rapid increase in IP3 formation consistent with the time course of production of an excitation-contraction coupling second messenger. However, inositol trisphosphate is not involved in the signal transduction pathway leading to pulmonary arterial contraction induced by hypoxia. PMID- 8447429 TI - Oxidant injury alters barrier function of ferret tracheal epithelium. AB - To understand the influence of oxidant stress on the barrier function of airway epithelium, we conducted studies to determine the effects of chemically generated reactive oxygen species on permeability, permselectivity, and active ion transport of ferret trachea. We examined the consequences of oxidant injury using ferret trachea mounted in Ussing-type chambers and bathed with a modified Krebs Henseleit solution containing mannitol and xanthine. We added xanthine oxidase to the luminal bathing solution, which reacted with the xanthine to generate reactive oxygen species. Tissue electrical conductance and short-circuit current were significantly increased after the addition of xanthine oxidase. Simultaneous measurement of mannitol flux (as a marker of paracellular conductance) and the backflux of chloride (lumen to submucosa) demonstrated a significant oxidant induced increase in mannitol flux and backflux of chloride. Mannitol flux and the backflux of sodium (submucosa to lumen) also increased after oxidant stress. Comparison of the diffusion of sodium relative to the diffusion of chloride in relation to predicted diffusion in free solution indicated that the paracellular pathway was cation selective after oxidant stress. Active ion transport, as reflected by the short-circuit current, was significantly increased transiently after oxidant stress. Studies with furosemide, amiloride, and diphenylamine-2 carboxylate are suggestive that oxidant stress transiently stimulates the Na-K ATPase. These studies demonstrated that exposure to reactive oxygen species significantly altered the permeability of the tracheal epithelium as well as active ion transport. PMID- 8447430 TI - Tubule formation by human surface respiratory epithelial cells cultured in a three-dimensional collagen lattice. AB - Human surface respiratory epithelial (HSRE) cells from nasal polyps have been cultured within collagen lattices in a serum-free defined medium. Cell growth observed over a period of 12 days showed a population doubling time of 36 h. Under these culture conditions, we observed a contraction of the lattices. Phase contrast light microscopy and transmission electron microscopy demonstrated that the HSRE cells formed tubular ductlike structures. Lumens formed by HSRE cells were surrounded by cuboidal-shaped polarized cells with numerous ciliated cells, secretory cells, and undifferentiated cells. Epidermal growth factor (EGF) was observed to stimulate the tubule formation and the contraction of the lattices. Videomicroscopic observations and analysis of the ciliary beating frequency (CBF) demonstrated that the cilia were homogeneously distributed on the whole apical surface of the ciliated cells and that their movement was well coordinated, with a CBF similar to that observed in outgrowth cells from cultured human nasal and tracheal epithelia. Immunofluorescent staining of basement membrane components synthesized and secreted by cells revealed the presence of type III collagen around the tubules. Type IV collagen and laminin were present in the cytoplasm and at the periphery of the cells. The biotin-streptavidin-gold immunocytochemical technique with monoclonal anti-mucin antibody showed intracellular localization of mucins in secretory granules of the secretory cells. With the use of substrate gel electrophoresis polyacrylamide gels impregnated with gelatin, collagenase activity was detected in the conditioned medium of the cultured HSRE cells. These results suggest that both three dimensional collagen gel and soluble factors such as EGF regulate tubule formation by HSRE cells. Moreover, the capacity of the epithelial cells to contract the gel suggests they may be involved in the wound healing process. PMID- 8447431 TI - Calcium transport in renal epithelial cells. AB - Extracellular calcium homeostasis involves coordinated calcium absorption by the intestine, calcium resorption from bone, and calcium reabsorption by the kidney. This review addresses the mechanism and regulation of renal calcium transport. Calcium reabsorption occurs throughout the nephron. However, distal tubules are the nephron site at which calcium reabsorption is regulated by parathyroid hormone, calcitonin, and 1 alpha,25-dihydroxyvitamin D3 and where the magnitude of net reabsorption is largely determined. These and related observations underscore the view that distal tubules are highly specialized to permit fine regulation of calcium excretion in response to alterations in extracellular calcium levels. Progress in understanding the mechanism and regulation of calcium transport has emerged from application of single cell fluorescence, patch clamp, and molecular biological approaches. These techniques permit the examination of ion transport at the cellular level and its regulation at subcellular and molecular levels. This editorial review focuses on recent and emerging observations and attempts to integrate them into models of cellular calcium transport. PMID- 8447432 TI - TGF-beta stimulates rat mesangial cell proliferation in culture: role of PDGF beta-receptor expression. AB - Transforming growth factor (TGF)-beta is known to increase mesangial cell (MC) matrix; however, its possible role on MC proliferation is controversial. We therefore studied the influence of TGF-beta on MC proliferation in culture and evaluated its effect on the platelet-derived growth factor (PDGF) B-chain as well as the expression of the PDGF beta-receptor. TGF-beta (1 ng/ml) increases MC DNA synthesis by approximately threefold after 48 h of incubation. TGF-beta-induced MC proliferation was also confirmed by cell counts. A neutralizing anti-TGF-beta antibody completely blocked this growth promoting activity. The levels of PDGF beta-receptor steady-state mRNA were increased by TGF-beta at 48 h. This was associated with an increase in receptor density per cell as measured by receptor kinetic studies. PDGF B-chain mRNA was also increased by TGF-beta at 48 h. A neutralizing anti-PDGF B-antibody causes no reduction of TGF-beta-induced DNA synthesis; however, suramin completely inhibited the mitogenic effect of TGF beta. We conclude that TGF-beta stimulates MC growth in long-term culture, a process in which upregulation of the PDGF beta-receptor and enhanced synthesis of PDGF B-chain might be involved. PMID- 8447433 TI - Urinary sodium excretion in chronic caval dogs after combined infusions of mannitol and ANP. AB - We studied the natriuretic effects of a combined mannitol and atrial natriuretic peptide (ANP) infusion in chronic caval dogs (TIVC) either responsive or unresponsive to an initial ANP infusion (75 ng.kg-1.min-1). The increment in urinary Na+ excretion (delta UNaV) to the initial ANP infusion in 11 TIVC responders was 127 and 1 mu eq/min in 7 nonresponders. A modest mannitol dose was then infused so as to augment distal Na+ delivery to the distal nephron but not flood the terminal inner medullary collecting duct (IMCD) with enormous quantities of salt and water. After mannitol, UNaV was 26 +/- 8 mu eq/min in TIVC responders and 24 +/- 4 mu eq/min in nonresponders. In these two groups of dogs, delta UNaV after manitol was 13 and 10 mu eq/min, respectively, from the previous experimental phase. During this stable mannitol-induced modest natriuresis, ANP was reinfused at initial dose levels. In TIVC responders, delta UNaV was 186 mu eq/min, a value greater than that obtained initially (P < 0.05), and delta UNaV in nonresponders was now 52 mu eq/min (P < 0.05). Because control and postmanitol UNaV was equivalent for each group, in the face of similar levels of glomerular filtration rate, blood pressure, and renal perfusion, it is difficult to conclude that only augmented delivery of Na+ to the IMCD converted TIVC nonresponders into responding dogs after mannitol and ANP. Other modulating factors may be involved. PMID- 8447434 TI - Locally produced EDRF controls preglomerular resistance and ultrafiltration coefficient. AB - During systemic acute blockade of endogenous endothelial-derived relaxing factor (EDRF) with N-monomethyl-L-arginine (NMA), a significant rise in arterial blood pressure (BP) occurred in the anesthetized rat. Renal vasoconstriction was also seen, with complex changes in glomerular hemodynamics; both preglomerular (RA) and efferent arteriolar (RE) resistances increased, producing a fall in glomerular plasma flow (QA) and a rise in glomerular blood pressure (PGC). The glomerular capillary ultrafiltration coefficient (Kf) was reduced. The net effect was a small fall in single-nephron glomerular filtration rate (SNGFR). To determine the effects of local EDRF blockade, two additional groups were studied with intrarenal administration of NMA; in the first series, one-tenth of the systemic dose was given, which produced no change in BP, a small renal vasoconstriction with an increase in RA, but no change in RE; thus PGC was unaffected. Kf fell, and a small reduction in SNGFR was seen. With a larger intrarenal dose of NMA (one-fifth systemic) a moderate rise in BP occurred, but only RA rose; RE and PGC were unaffected, and Kf and SNGFR fell. These observations suggest that locally produced EDRF controls RA and Kf and that a rise in RE and PGC is only seen with systemic EDRF blockade when a large rise in BP occurs. PMID- 8447435 TI - Effects of calcitonin on function of intercalated cells of rat cortical collecting duct. AB - In the rat cortical collecting duct (CCD), the presence of highly specific receptors to calcitonin (CT) coupled to a sensitive adenylate cyclase system suggests that this segment is a target site for CT. Our aim was to explore the effects of CT on the rat CCD microperfused in vitro. The hormone failed to alter the osmotic water permeability and did not affect net Na+ transport but generated a lumen-positive transepithelial potential difference (PDte), which under control conditions was close to zero. This response was dose dependent and was still observed in the presence of luminal amiloride, despite the luminal positivity generated by the Na+ channel blocker (PDte increased from 4.0 +/- 0.8 to 9.5 +/- 1.1 mV). In contrast, the nominal absence of CO2/HCO3- or the use of a low-Cl- solution totally prevented the PDte changes caused by CT. The CT-induced lumen positive PDte was reduced by 2.3 +/- 0.8 mV after the basolateral addition of the Cl- channel inhibitor diphenylamine-2-carboxylate. 4-Acetamido-4' isothiocyanostilbene-2,2'-disulfonic acid and acetazolamide, which inhibit Cl /HCO3- exchangers and carbonic anhydrase activities, respectively, also inhibited the CT-induced PDte by 4.6 +/- 0.5 and 5.0 +/- 0.9 mV. To test whether the acid base status of the animals influences the response to CT, rats underwent an acid or alkali load. CCD dissected from acid-loaded rats responded to CT to the same extent as control animals, but the hormonal action was significantly attenuated when the CCD was harvested from alkali-loaded rats (PDte increases: acid 4.0 +/- 0.3 vs. alkali 1.6 +/- 0.6 mV, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447436 TI - Role of Na-dependent Cl/HCO3 exchange in basolateral Cl transport of rabbit proximal tubules. AB - To analyze the rate of basolateral Cl exit and the magnitude and relative contributions of KCl cotransport and Na-dependent and -independent Cl/HCO3 exchange to Cl exit across the basolateral membrane (BLM) during transcellular Cl absorption, rabbit proximal convoluted tubules (PCT) were perfused with high-Cl, low-HCO3 plus formate solutions and bathed with plasma ultrafiltrate-like plus formate solutions. The initial rates of intracellular Cl activity (AiCl) reduction following bath Cl removal were compared when bath Cl was 0, when bath Na and Cl were 0, and when bath HCO3 and Cl were 0. The initial rate of AiCl reduction following bath Cl removal was 4.4 +/- 0.4 mM/s. After bath Na and Cl removal, this rate was reduced to 25.1 +/- 5.0%. After bath HCO3 and Cl removal, it was reduced to 18.0 +/- 4.8%. The difference between bath Na and Cl removal and bath HCO3 and Cl removal was not significant. Cl efflux following bath HCO3 and Cl removal may be due to a KCl symporter. The contribution of a KCl symporter was examined by raising bath K to 20 mM, thus eliminating the chemical driving force for KCl exit. After bath K increase, the initial rate of AiCl increase was 0.057 +/- 0.005 mM/s. These data suggest that Cl efflux at BLM of rabbit PCT is 1) large enough to explain transcellular Cl transport, 2) predominately due to an Na-dependent Cl/HCO3 exchanger, and 3) negligibly due to an Na-independent Cl/HCO3 exchanger or a KCl symporter. PMID- 8447437 TI - Expression of dopamine D1A receptor gene in proximal tubule of rat kidneys. AB - The existence of dopamine receptor subtypes outside the central nervous system has been suggested by pharmacological and biochemical techniques. Whether the renal dopamine receptors are distinct from those cloned from the brain remains to be determined. Indeed, the expression of any of these receptor genes in the kidney has not been demonstrated definitively. In this study, we amplified D1A receptor cDNA from microdissected proximal convoluted tubules of the rat kidney by reverse transcription-polymerase chain reaction; primers were based on the sequence of rat D1A cDNA cloned from the brain and corresponded to the third cytoplasmic loop of the receptor. Specificity of the amplified products was verified by restriction analysis, Southern blots, and sequencing. Furthermore, solution hybridization indicated the presence of a single ribonuclease-protected RNA species corresponding to the D1A receptor mRNA in proximal tubules. These studies report for the first time the presence of D1A receptor message in the kidney. PMID- 8447438 TI - Characterization of renal aldosterone receptors in genetically hypertensive rats. AB - To investigate the aldosterone responsiveness of genetically hypertensive rats, we compared characteristics of renal cytosolic aldosterone receptors from the M strain of stroke-prone, spontaneously hypertensive rats (M-SHRSP) with normotensive Wistar-Kyoto rats (WKY). In M-SHRSP, blood pressure was elevated significantly at 6 wk of age, when their plasma aldosterone concentrations were similar to those in WKY. Decreases in urine volume and sodium excretion were also observed in M-SHRSP. At 10 wk of age, M-SHRSP plasma aldosterone concentrations became significantly higher than those in WKY. On the other hand, the concentration of renal cytosolic aldosterone receptors (type I, aldosterone specific) had already increased at 6 wk of age in M-SHRSP, with no difference in affinity, and levels remained increased thereafter. There were no significant differences in molecular weights or ionic charges of either "activated" or "non activated" aldosterone-receptor complexes between M-SHRSP and WKY, indicating that the molecular properties were similar in both groups. These results suggest that the increased concentration of aldosterone receptors in the kidneys of M SHRSP might increase their aldosterone responsiveness and contribute to the development of high blood pressure in these animals. PMID- 8447439 TI - Thromboxane binding and signal transduction in rat glomerular mesangial cells. AB - Thromboxane A2 (TxA2) stimulates contraction of glomerular mesangial cells. However, mesangial cell TxA2 receptors have not been previously characterized. We therefore investigated TxA2 binding and TxA2-associated signal transduction pathways in rat glomerular mesangial cells using the specific thromboxane receptor agonist (1S-[1 alpha,2 beta(5Z),3 alpha-(1E,3S)4 alpha])-7-(3-[3-hydroxy 4-(p- iodophenoxy)-1-butenyl]7-oxabicyclo[2.2.1]hept-2-yl)-5-heptenoic acid (IBOP). In these cells, [125I]BOP binding was saturable, displaceable, and of high affinity. Scatchard analysis revealed a single class of binding sites with a dissociation constant (Kd) of 293 pM and a maximal density of binding sites (Bmax) of 33 fmol/mg protein. Specific binding was inhibited by the thromboxane agonist (15S)-hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5Z,13E-dienoic acid (U-46619) [inhibitor dissociation constant (Ki) = 297 nM] and the TxA2 receptor antagonists SQ 29548 (Ki = 1 nM) and (1R-[1 alpha(Z),2 beta,3 beta,5 alpha])-(+) 7-(5-[(1,1'-biphenyl)- 4-yl-methoxy]-3-hydroxy-2-(1-piperidinyl)cyclopentyl]-4 heptenoic acid (GR 32191) (Ki = 92 nM). Binding was also highly specific for thromboxane because prostaglandin E2 (Ki = 16 microM) and the inactive thromboxane metabolite, TxB2 (Ki = 41 microM), were approximately 1,000-fold less potent at inhibiting binding. IBOP stimulated phosphatidylinositol hydrolysis with an effective concentration of drug that produces 50% of the maximal response of 229 pM, which correlated well with the equilibrium Kd and enhanced phosphorylation of an acidic 80-kDa protein substrate for protein kinase C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447440 TI - Autoxidation of cysteine generates hydrogen peroxide: cytotoxicity and attenuation by pyruvate. AB - The reactivity of cysteine presents a paradox: although regarded as an antioxidant, cysteine interacts with oxygen in a metal-catalyzed reaction to produce reactive species. Because ischemia provokes the appearance of millimolar amounts of cysteine and increased amounts of transition metals, we studied whether cysteine, in the presence of transition metals, consumes oxygen, generates hydrogen peroxide, and is toxic. Using fluorescence cytometry, we provide direct evidence that hydrogen peroxide is copiously generated during cysteine autoxidation. Pyruvate attenuates such generation of hydrogen peroxide and cytotoxicity. Cysteine oxidation is stimulated by an EDTA-chelatable diethyl dithiocarbamate-chelatable constituent of kidney extract; this suggests that copper is the catalytically active metal. The toxicity resulting from cysteine oxidation is less than that induced by amounts of reagent hydrogen peroxide that produce comparable fluorescence. Cysteine also prevents hydrogen peroxide-induced toxicity. Thus, although cysteine generates hydrogen peroxide, it can guard against hydrogen peroxide toxicity, possibly by binding metals on which the toxicity of hydrogen peroxide is dependent. Thus the behavior of cysteine can be salutary or pernicious; the net effect of cysteine, within this wide ambit of actions, is decisively influenced by the conditions to which cysteine is exposed. PMID- 8447441 TI - Autoregulation of intravascular pressure in preglomerular juxtamedullary vessels. AB - To quantify the functional significance of autoregulatory responses in preglomerular juxtamedullary (JM) vessels, intravascular pressures (P chi) were measured with a servonull instrument in blood-perfused arcuate (ArcA) and interlobular arteries (ILA), afferent arterioles (AA), and glomerular capillaries (GC) in vitro. P chi was determined at perfusion pressures (Pp) between approximately 60 and 150 mmHg, and the slope of the relationship between Px and Pp was estimated by linear regression. From the regression, Px was 98 +/- 1, 96 +/- 2, 64 +/- 9, and 48 +/- 2 mmHg for ArcA, ILA, AA, and GC, respectively, at the reference perfusion pressure of 100 mmHg. The results show good autoregulation of GC pressure (Pg), with a response slope of 0.10 +/- 0.07 mmHg per mmHg change in Pp, corresponding to an autoregulation index of 0.20 +/- 0.15. The slopes of the Px vs. Pp relationships in ArcA, ILA, and AA were 0.96 +/- 0.02, 0.79 +/- 0.08, and 0.32 +/- 0.11, respectively. To determine whether these observed relationships in preglomerular vessels reflect significant upstream resistance changes, we derived a new autoregulation index for Px measured at an arbitrary preglomerular location. This analysis takes into account the extent to which outflow pressure, Pg, is autoregulated by the ensemble action of the entire preglomerular vasculature. The analysis indicates that 20% autoregulatory compensation occurs upstream from the late ILA, 65% upstream from the late AA, and 80% for the entire preglomerular vascular tree. Hence, in the JM preglomerular circulation, the AA is the major site of autoregulatory resistances adjustment, with a smaller but significant contribution by the ILA. PMID- 8447442 TI - Bradykinin: potential for vascular constriction in the presence of endothelial injury. AB - Bradykinin (BK), a known vasodilator in vivo, and arginine vasopressin (AVP), a vasoconstrictor in vivo, both stimulate a rise in cytosolic free Ca2+ ([Ca2+]i) in vascular smooth muscle cells (VSMC). The present study was undertaken to investigate this apparent paradox. The following three possibilities were examined, namely, 1) signaling events other than [Ca2+]i are different for BK and AVP; 2) BK, but not AVP, stimulates prostaglandins in VSMC, thus resulting in divergent effects on VSMC tone; and 3) AVP and BK exhibit qualitatively similar effects on VSMC signal transduction but divergent effects on VSMC tone are mediated by endothelial events. The results demonstrated that BK stimulated a rise in inositol trisphosphate (IP3), [Ca2+]i, 45Ca2+ efflux, and Ca2+ influx and a biphasic change in intracellular pH when N-2-hydroxyethylpiperazine-N'-2 ethanesulfonic acid-buffered solution was used. The BK-induced VSMC contraction was also comparable to that observed with AVP. The cyclooxygenase inhibitor, meclofenamate, enhanced the effect of both BK and AVP on VSMC tone, as assessed by shape change, by a comparable degree. BK, but not AVP, stimulated endothelial cells to release a substance that blocked the contractile response of BK and AVP. Methylene blue, a blocker of cytosolic guanylate cyclase and therefore of the production of guanosine 3',5'-cyclic monophosphate (2nd messenger of endothelium derived relaxing factor, EDRF), and nordihydroguaiaretic acid, an inhibitor of EDRF, both prevented this endothelium-dependent effect of BK. These results therefore indicate that BK is a constrictor of VSMC, an effect that can be overridden by the hormone's endothelial effect to stimulate the release of a vasodilator(s), which is most likely EDRF. PMID- 8447443 TI - In vitro perfusion of chinchilla thin limb segments: urea and NaCl permeabilities. AB - We measured the urea and NaCl permeabilities (Purea and PNaCl, respectively) of the following nephron segments from chinchilla: the upper part of the long-loop descending limb (from outer medulla, LDLu), the middle part of the long-loop descending limb (from outer 30% of the inner medulla, LDLm), the lower part of the long-loop descending limb (from deep inner medulla, LDLl), and the thin ascending limb (from deep inner medulla, ATL). We found that Purea (x10(-5) cm/s) was relatively low in the LDLu (3.3), but that the value was larger in the inner medullary thin descending limb (16.8 for LDLm and 47.6 for LDLl). The ATL had an even higher value (170). Phloretin, 0.25 mM, added to the peritubular bath had no effect on Purea of these segments, suggesting that the rapid transport rate is not due to a phloretin-sensitive facilitated transport pathway like that seen in the inner medullary collecting duct. PNaCl (x10(-5) cm/s) also increased with distance along the length of the thin descending limb (LDLu, 11.7; LDLm, 41.2; LDLl, 98.4; and ATL, 321). Calculations from NaCl dilution potential measurements showed that LDLu was Na+ permselective, whereas LDLl and ATL were Cl- permselective. High solute permeabilities in the inner medullary thin descending limb contradict a major requirement of the passive model of urinary concentration developed previously (J. P. Kokko and F. C. Rector, Jr. Kidney Int. 2: 214-223, 1972; and J. L. Stephenson. Kidney Int. 2: 85-94, 1972). PMID- 8447444 TI - Metabolic clearance of vasopressin and an analogue resistant to vasopressinase in human pregnancy. AB - The metabolic clearance rate (MCR) of arginine vasopressin (AVP) increases fourfold during human pregnancy. To explore whether circulating vasopressinase may play a role in this change, six women underwent a three-tier infusion clearance study, twice, in random order, to determine the MCRs of either AVP or 1 deamino-8-D-AVP (dDAVP, an analogue resistant to degradation by vasopressinase). Volunteers were tested in late pregnancy (LP), 24-48 h postdelivery (PD), and 5-6 (PP1) and 10-12 (PP2) wk postpartum, thus examining MCRs when vasopressinase levels were high, before and after removal of the placenta (LP and PD), and when plasma enzyme activity was becoming (PP1) and became (PP2) undetectable. Manipulation of infusate permitted comparison of MCRs at three plasma levels whose range was similar at each test period. PAVP and PdDAVP (2.2 and 10 pg/ml, respectively, during the initial infusion) increased to 8 and 31 pg/ml, stepwise increments that had no influence on respective MCRs (AVP: 3.4, 2.2, 0.77, and 0.67 l/min during LP, PD, PP1, and PP2 compared with 0.18, 0.21, 0.17, and 0.15 l/min for dDAVP). Comparison of similar and submaximal urinary osmolality revealed PdDAVP values three- to fourfold greater than PAVP. Von Willebrand factor (VWF) and factor VIIIc levels increased almost fourfold in response to dDAVP during pregnancy, but only doubled in the nonpregnant state; these differences did not reach significance. We conclude that although AVP disposal rates increase fourfold in pregnancy, those of dDAVP change little, suggesting a role of vasopressinase in the increased MCR of AVP in gestation (as well as in the genesis of certain polyuric disorders of pregnancy).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447445 TI - Basolateral K+, Cl-, and HCO3- conductances and cell volume regulation in rabbit PCT. AB - The relationship between changes in cellular volume, intracellular pH (pHi), basolateral membrane potential (VBL), and membrane partial basolateral conductances to K+ (tK) and Cl- (tCl) and mediated by the Na-HCO3 cotransporter (tNaHCO3) was determined in the collapsed proximal convoluted tubule (PCT) submitted to a 125-mosmol/kg hypotonic shock. The shock that produces a rapid swelling followed by partial volume regulation was accompanied by a rapid and transient VBL hyperpolarization of 10.0 +/- 1.5 mV and a second gradual hyperpolarization of 5.0 +/- 0.7 mV with respect to a control value of -44.0 +/- 4.6 mV.tK was 0.12 +/- 0.03 in control, increased transiently to 0.15 +/- 0.03, and then gradually increased to reach 0.32 +/- 0.06 at the end of hypotonic shock. In contrast, tCl was 0.03 +/- 0.01 in control, increased rapidly to a maximum of 0.16 +/- 0.01, and then decreased slowly to 0.08 +/- 0.02. During the same period, tNaHCO3 decreased rapidly from 0.41 +/- 0.04 to a minimum of 0.11 +/ 0.02 and slowly reincreased to reach 0.16 +/- 0.01.pHi increased transiently from 7.09 +/- 0.03 in control to 7.24 +/- 0.05 to come back gradually to 7.15 +/- 0.05 at the end of the hypotonic period. The membrane absolute conductance mediated by the Na-HCO3 cotransporter was found to increase only slightly in hypotonic conditions, whereas that to K+ and Cl-, GK and GCl, increased by at least factors of 8 and 17, respectively, with the increase of GCl being much faster than that of GK. In addition, the temporal variations in GCl followed closely those of the cellular water efflux. We conclude that the hypotonic swelling leads to important increases in the conductive pathways for K+ and Cl- and that the Cl- conductance pathway appears to be the rate limiting step in triggering and supporting regulatory volume decrease. PMID- 8447446 TI - Heterogeneity of the hypoxic state in rat heart is determined at capillary level. AB - Heterogeneity in the hypoxic state of Tyrode-perfused rat hearts was studied using NADH and Pd-porphine videofluorometry. Ischemic as well as high-flow anoxia resulted in a homogeneous rise of tissue NADH fluorescence, whereas normoxic recovery from both types of anoxia caused transiently persisting patchy fluorescent areas. Patterns were always the same for a given heart. PO2 distribution in the vasculature measured by Pd-porphine phosphorescence showed patterns similar to the NADH fluorescence patterns. Microsphere embolization of the capillaries, but not of arterioles, elicited identical NADH fluorescence patterns as seen during recovery from anoxia without microspheres. High heartbeat rates also caused patchy fluorescent areas but not in the presence of adenosine. Patterns corresponded to those seen during normoxic recovery from anoxia under low beat rates. It is concluded that there are circulatory units in the rat heart at the capillary level that result in the temporary persistence of anoxic areas during recovery from anoxia. These vulnerable areas are the first to be compromised during high heartbeat rates. PMID- 8447448 TI - Role of PGI2 and epoxyeicosatrienoic acids in relaxation of bovine coronary arteries to arachidonic acid. AB - Metabolites of arachidonic acid regulate several physiological processes, including vascular tone. The purpose of this study was to determine which metabolites of arachidonic acid are produced by bovine coronary arteries and which may regulate coronary vascular tone. Arachidonic acid induced a concentration-related, endothelium-dependent relaxation [one-half maximum effective concentration (EC50) of 2 x 10(-7) M and a maximal relaxation of 91 +/- 2% at 10(-5) M] of bovine coronary arteries that were contracted with U-46619, a thromboxane mimetic. The concentration of 6-ketoprostaglandin F1 alpha (6-keto PGF1 alpha), a metabolite of prostaglandin I2 (PGI2), increased from 82 +/- 6 to 328 +/- 24 pg/ml with arachidonic acid (10(-5) M). Treatment with the cyclooxygenase inhibitor indomethacin attenuated arachidonic acid-induced relaxations by approximately 50% and blocked the synthesis of 6-keto-PGF1 alpha. PGI2 caused a concentration-related relaxation (EC50 of 10(-8) M and a maximal relaxation of 125 +/- 11% at 10(-7) M). BW755C, a cyclooxygenase and lipoxygenase inhibitor, inhibited arachidonic acid-induced relaxation to the same extent as indomethacin. When vessels were treated with both indomethacin and BW755C, the inhibition of relaxation was the same as either inhibitor alone. SKF 525a, a cytochrome P-450 inhibitor, reduced arachidonic acid-induced relaxation by approximately 50%. When SKF 525a was given in combination with indomethacin, the relaxation by arachidonic acid was almost completely inhibited. SKF 525a inhibited the synthesis of epoxyeicosatrienoic acids (EETs).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447447 TI - Maturational changes in endothelium-derived relaxations in newborn piglet pulmonary circulation. AB - It is accepted knowledge that the endothelium can profoundly affect vascular tone through the release of vasoactive substances. The maturational changes in the role of the endothelium-derived relaxing factor (EDRF) and ATP-dependent K+ channels in the neonatal pulmonary circulation were investigated in isolated perfused lungs from 1- and 7-day-old piglets. The EDRF inhibitor, N omega-nitro-L arginine (L-NNA), had potent dose-dependent constrictor effects on the pulmonary vasculature with normal and raised tone. The constrictor effect of L-NNA was greater (P < 0.05) in the 1-day-old than in the 7-day-old lungs and was significantly (P < 0.005) attenuated by pretreatment with the EDRF precursor, L arginine. Furthermore, we studied the possibility of developmental changes in the sensitivity of smooth muscle cells to EDRF by testing sodium nitroprusside, nitric oxide, and 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP). All caused a decrease in perfusion pressure, but only sodium nitroprusside elicited a greater (P < 0.01) effect in the 1-day-old. Endothelin-1 (ET-1) and bradykinin (BK) elicited dilator responses that were significantly (P < 0.05) reduced in the presence of L-NNA. Interestingly, the dilator response to ET-1 was more marked (P < 0.001) in the younger group, whereas no age difference was noted with BK. Finally, lemakalim, a K+ channel activator, caused a vasodilation of equal magnitude at both ages. In summary, EDRF and ATP-dependent K+ channels appear to play a role in the control of the newborn piglet pulmonary vasculature.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447449 TI - Complement C5a-mediated myocardial ischemia and neutrophil sequestration: two independent phenomena. AB - The intracoronary infusion of complement C5a causes a decrease in coronary blood flow and contractile dysfunction mediated by thromboxane (TxA2) and leukotrienes. Although these effects are accompanied by polymorphonuclear leukocyte (PMN) sequestration, the role of PMNs and the source of these eicosanoids remain unknown. To assess the contribution of PMNs to the C5a-induced myocardial ischemic response, the left anterior descending (LAD) coronary artery of pigs (n = 13) was cannulated and pump perfused at constant pressure with either normal arterial blood or neutropenic arterial blood (PMN count 0.02 x 10(3) cells/microliters) obtained from animals treated with cyclophosphamide (50 mg/kg iv, given 4 days before). The coronary vein draining the LAD region was cannulated for measurement of leukocyte count and TxB2 levels. Two groups of animals were studied: group 1 (n = 7) neutropenic animals were instrumented and normal animals served as blood donors and group 2 (n = 6) normal animals were instrumented and neutropenic animals served as blood donors. The myocardial response to intracoronary C5a (500 ng) was determined in each animal during coronary perfusion with normal arterial blood and also with neutropenic arterial blood. During perfusion with normal arterial blood, C5a decreased coronary flow to 52.3% and contractile function to 58.8% of preinfusion values. This was accompanied by a transient myocardial accumulation of PMNs (arterial-coronary venous gradient of 5.4 x 10(3) cells/microliters) and increased TxB2 levels in coronary venous blood (from 0.31 to 17.5 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447450 TI - Effect of captopril on sympathetic preganglionic efferent activity in cats. AB - In 13 decerebrate cats, we studied the effects of captopril (10 mg/kg iv bolus) on the background discharge of thoracic preganglionic sympathetic fibers. After drug administration there was an initial reduction in systolic arterial pressure (SAP), which was followed by a later inhibition of sympathetic discharge (from 2.7 +/- 0.5 to 0.79 +/- 0.1 imp/0.1 s; P < 0.01). Captopril significantly reduced the excitatory response of sympathetic fibers to premature ventricular contraction (70 +/- 17 vs. 257 +/- 30%), inferior vena cava obstruction (176 +/- 56 vs. 315 +/- 85%) and asphyxia (143 +/- 20 vs. 245 +/- 51%). Vice versa the sympathetic response to aortic occlusion was unaffected (-58 +/- 8 vs. -62 +/- 6%). A similar reduction in sympathetic discharge was observed after captopril administration in anesthetized cats (n = 3). On the contrary, no changes in background neural discharge were noticed in decerebrate-spinalized cats (n = 5), despite comparable hemodynamic effects. These data indicate that captopril reduces sympathetic efferent activity and its responsiveness to excitatory stimuli. The lack of neural effects in decerebrate-spinalized cats is consistent with a brain stem site of action of captopril. PMID- 8447451 TI - Tachyphylaxis to the vasopressor effects of endothelin in rat aortic rings. AB - Endothelin-1 (ET-1), a potent vasoconstrictor peptide released by endothelial cells, binds with high affinity to surface receptors and is highly resistant to dissociation. We observed tachyphylaxis to the pressor effects of a second application of ET-1 in rat aortic rings and investigated the mechanism of this effect. Developed tension increased progressively with doses of ET-1 ranging from 1 to 500 nM (P < 0.001), and tensions with rechallenge were correspondingly decreased (P < 0.001). In response to 500 nM ET-1, tension increased 1,599 +/- 72 (SE) mg/mg ring wt. Rechallenge with 500 nM ET-1 led to contraction of only 33 +/ 40 mg/mg ring wt. Tachyphylaxis was seen up to 6 h after initial challenge. Pretreatment with nicardipine, lidoflazine, nitroglycerin, and sphingosine did not affect tachyphylaxis. Pretreatment with 500 microM dansylcadaverine (an inhibitor of endothelin internalization) markedly inhibited ET-1-induced contraction and also inhibited tachyphylaxis to ET-1. Further studies with radiolabeled ET-1 suggested that subsequent ET-1 binding is markedly decreased after an initial ET-1 challenge. Dansylcadaverine inhibited ET-1 internalization and also inhibited the decreased binding seen with ET-1 rechallenge. Rat aortic rings demonstrate tachyphylaxis to the pressor effect of a second dose of ET-1. The mechanism appears to be related to binding and subsequent internalization of endothelin-receptor complexes. This effect suggests a possible mechanism for sustained decreases in systemic vascular resistance. PMID- 8447452 TI - Myocardial responses to isoproterenol are altered by chronic alcoholism and infection. AB - Alcohol, consumed as 36% of the caloric intake for 8-10 wk, causes a potentiation of cardiac dysfunction induced by a second insult, sepsis. Because chronic alcoholism may attenuate the responsiveness of the myocardium to catecholamine stimulation, and because catecholamine support seems to be essential for the myocardium to generate an adequate cardiac output in sepsis, we hypothesized that the heart from the alcoholic septic rat would show a compromised inotropic responsiveness to catecholamines compared with the heart from the nonalcoholic septic rat. To test this hypothesis, rats were fed an ethanol-containing or control liquid diet for 8-10 wk and were then made septic with live Escherichia coli (10(10) E. coli) through a dorsal subcutaneous catheter. The next day, hearts were removed and perfused at a constant hydrostatic pressure, and a compliant balloon was placed in the left ventricule for measurement of pressure (LVP). Hearts were paced at 350-360 beats/min. Hearts were allowed to stabilize for 15 min, and then the response to a submaximal dose of isoproterenol (Iso) was measured. Hearts recovered for 30 min, at which time the response to a maximum dose of Iso was recorded. Basal (pre-Iso) LVP was lower in the control septic and alcoholic septic groups than in the control and alcohol groups. However, the maximum increase in LVP in response to Iso was greater in the two septic groups than in the two nonseptic groups. The peak LVP in response to Iso was similar in the control, septic, and alcoholic septic groups, and was significantly greater than in the alcohol group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447453 TI - Endothelium-dependent response of human internal mammary artery to hypoxia. AB - To study the effect of hypoxia on vascular tone in human internal mammary artery (IMA), segments of IMA were suspended in organ chambers and contracted with norepinephrine (at a dose producing 30% of maximal contraction). Exposure of IMA segments with endothelium to hypoxia (partial pressure of oxygen, 38 +/- 4 mmHg) resulted in a transient relaxation (47 +/- 6%) followed by constriction (177 +/- 8%) (n = 14). IMA segments without endothelium exhibited a gradual decrease in tension that almost completely counteracted vasoconstriction. The initial transient endothelium-dependent relaxation could be blocked by indomethacin (10( 6)M) and was associated with a 51% increase in 6-ketoprostaglandin F1 alpha production (n = 22, P < 0.05). The endothelium-dependent contraction to hypoxia could be attenuated by indomethacin (n = 6, P < 0.05) or NG-monomethyl-L-arginine (10(-5)M; n = 9, P < 0.05) and was completely blocked by combination of these agonists (n = 6, P < 0.05). These experiments indicate that on exposure to hypoxia, the human IMA exhibits an initial prostacyclin-mediated relaxation followed by contraction due to the production of a constrictor prostanoid in addition to the inhibition of basal production of endothelium-derived relaxing factor. PMID- 8447454 TI - Transforming growth factor-beta attenuates ischemia-induced alterations in cerebrovascular responses. AB - We observed previously that 20 min of global cerebral ischemia followed by 45 min of reperfusion selectively blocked cerebral vasodilation to hypercapnia and hypotension. This study determines the effects of pretreatment with transforming growth factor-beta (TGF-beta) on cerebrovascular responses after cerebral ischemia in piglets equipped with closed cranial windows. Hypercapnia-induced pial arteriolar dilation was blocked after cerebral ischemia (20 +/- 1 vs. 2 +/- 1% dilation before and after ischemia, respectively). Similarly, the increases in periarachnoid cortical cerebrospinal fluid 6-ketoprostaglandin F1 alpha (6-keto PGF1 alpha) and prostaglandin E2 (PGE2) concentration in response to hypercapnia were blocked (2.5 +/- 0.2- vs. 0.2 +/- 0.4-fold and 2.1 +/- 0.1- vs. 0.3 +/- 0.4 fold increase in 6-keto-PGF1 alpha and PGE2, respectively). Treatment with topical TGF-beta (400 ng/ml) before and during ischemia-reperfusion attenuated the loss of hypercapnia-induced cerebrovascular dilation (20 +/- 1 vs. 14 +/- 1% dilation before and after ischemia, respectively) and the loss of associated changes in cerebrospinal fluid prostanoids (2.0 +/- 0.2- vs. 1.7 +/- 0.2-fold and 2.3 +/- 0.2- vs. 2.2 +/- 0.3-fold increase in 6-keto-PGF1 alpha and PGE2 before and after ischemia, respectively). The loss of cerebrovascular dilation in response to hemorrhagic hypotension after ischemia was similarly prevented by TGF beta. Cerebrovascular dilation to topical isoproterenol was unchanged after ischemia. TGF-beta may preserve endothelial cell function. We conclude that topical TGF-beta can attenuate cerebromicrovascular compromise caused by ischemia reperfusion in newborn pigs. PMID- 8447455 TI - Wall tension and myocardial dysfunction after ischemia and reperfusion. AB - Cell viability is maintained during prolonged ischemia (ISCH) in isolated heart systems because mechanical function is nil (acute hibernation). By contrast, a noncontracting ischemic segment in an in vivo heart exhibits irreversible damage after < or = 30 min. To explore this difference, isolated rabbit hearts were buffer perfused and exposed to elevations of ventricular balloon pressure (BP) during ISCH to mimic systolic stresses of a dyskinetic (DYSK) segment. Relationships of magnitude and duration of stress to recovery of systolic function and metabolism were assessed. After 30 min of reperfusion (R30) in hearts subjected to 90 min of ISCH [10% coronary flow (CF)] and BP = 0, peak systolic pressure (PSP) returned to 69% of control. With BP set at 120 mmHg, recovery was to only 24%. With BP = 80, PSP at R30 was 46%. Extent of recovery was inversely affected by the duration of elevated pressure. Tissue ATP was reduced from 18.5 to 3.7 and glycogen from 164 to 28 mumol/g in the BP = 120 group. CF and myocardial O2 consumption were reduced to 50% at R30; there was a threefold increase in wall stiffness. These data suggest that mechanical stress of DYSK contributes significantly to metabolic and functional deterioration of ischemic myocardium. PMID- 8447456 TI - Induction of NO production by TNF-alpha and lipopolysaccharide in porcine coronary arteries without endothelium. AB - The effects of tumor necrosis factor-alpha (TNF-alpha) and lipopolysaccharide (LPS) were studied in porcine coronary arteries without endothelium. Rings of the artery were incubated in minimum essential medium with TNF-alpha or LPS for 6 or 24 h. After 6 h incubation, the rings were suspended in organ chambers filled with physiological salt solution containing indomethacin for the measurement of isometric force. The rings were contracted with prostaglandin F2 alpha before the addition of L-arginine. In rings treated with TNF-alpha or LPS, L-arginine caused a concentration-dependent relaxation that was abolished by N omega-nitro-L arginine [an inhibitor of nitric oxide (NO) synthase]. However, contractions to 5 hydroxytryptamine were not affected by TNF-alpha and LPS. After 24 h of incubation, TNF and LPS impaired the contractions to 5-hydroxytryptamine and increased the accumulation of nitrite, a stable degradation product of NO. These effects of TNF-alpha and LPS were blocked by N omega-nitro-L-arginine. Cycloheximide (an inhibitor of protein synthesis) attenuated the inhibitory effect of TNF-alpha and LPS on contractions to 5-hydroxytryptamine. Thus, in the porcine coronary artery without endothelium, TNF-alpha and LPS can induce an L arginine-NO pathway. PMID- 8447457 TI - Pressure-flow characteristics of intramural and total coronary collateral networks. AB - The purpose of the present investigation was to determine the pressure-flow (PF) relationship of intramural collaterals and to determine whether their characteristics differ significantly from those of the total collateral network, defined as the epicardial plus intramural collateral network. Because a significant portion of the collateral flow is diverted away from the retrograde flow measurement, we embolized the coronary vessel on which the retrograde flow was measured with spheres of various sizes until the retrograde flow was maximized and retrograde flow diversion blocked. The PF relationship was obtained before and after the epicardial collaterals were cauterized to determine the characteristics of the total and intramural collateral network. PF data for the collateral circulations were obtained by changing the inflow pressure to all coronary vessels simultaneously and by measuring the retrograde flow while maintaining the retrograde outflow pressure at 0 mmHg. The PF characteristics of the total and intramural collateral circulations could be fitted by either a second-degree polynomial or linear equation. In both cases the pressure intercept crossed the origin of the axes. The average contribution of intramural collaterals to total retrograde flow was 58 +/- 5%. We conclude that the PF characteristics of intramural collaterals parallel those of the total collateral circulation. PMID- 8447458 TI - Mechanoelectrical feedback effects of altering preload, afterload, and ventricular shortening. AB - Electrophysiological consequences of altering ventricular load (mechanoelectrical feedback) were characterized in an isolated canine heart preparation. A computerized servo pump system controlled left ventricular volume and allowed ventricular ejection against a simulated arterial load (3-element Windkessel model). In 12 ventricles, end-diastolic volume (Ved) was held constant (end diastolic pressure 6-12 mmHg) as arterial resistance (R) was varied (0.5-12 mmHg.s.ml-1), but afterload-dependent changes in the monophasic action potential (MAP) were not observed despite a large stroke volume effect. In contrast, when R was held constant in eight ventricles while Ved was increased from 20 to 40 ml, the plateau phase of the MAP was abbreviated, the terminal portion of phase 3 repolarization was delayed, and MAP duration measured at 20, 70, and 90% repolarization decreased (P < 0.05). In six ventricles, immediate transitions from isovolumic to ejecting mode at constant Ved did not alter MAP duration, but the magnitude of early afterdepolarizations (EADs), observed during isovolumic beats at high Ved, was reduced with resumption of ventricular ejection. As stroke volume of the initial ejecting contraction was increased by stepwise reductions of R, the magnitude of the EADs decreased progressively. Thus altering ventricular afterload does not modulate action potential duration in ventricles subjected to elevated, physiological, or even greatly reduced levels of afterload, whereas diastolic filling to high Ved does. Under conditions that lead to reduced stroke volume and high end-systolic volume, EADs are produced that are virtually abolished when ventricular ejection fraction is normalized. PMID- 8447459 TI - Effects of afterload and heart rate on NAD(P)H redox state in the isolated rabbit heart. AB - NAD(P)H redox state was monitored using surface fluorescence in isolated, normothermic, working rabbit hearts under conditions of limited substrate (glucose alone) and abundant substrate (glucose + lactate). To alter work, afterload was varied between 75 and 150 cmH2O or heart rate was increased in steps until no further increase in myocardial oxygen consumption (MVO2) occurred. Alterations in afterload did not cause a significant change in NAD(P)H fluorescence. Progressive increases in heart rate did not alter NAD(P)H emission until MVO2 began to decline (approximately 300 beats/min), ventricular performance decompensated, and there was evidence of ischemia, at which time NAD(P)H fluorescence increased. Although the addition of 3 mM lactate to the perfusate resulted in a rapid increase in NAD(P)H fluorescence, NAD(P)H fluorescence still did not respond to altered workload. The results suggest that NAD(P)H redox state is not the primary stimulus for increased myocardial respiration secondary to tachycardia or afterload. However, despite increased rates of cardiac work, NAD(P)H was maintained at a relatively stable level, suggesting that reducing equivalent supply to the electron transport chain increases in parallel with increased MVO2. PMID- 8447460 TI - Microvascular hemodynamics in the sickle red blood cell perfused isolated rat lung. AB - In this study the effects of alveolar hypoxia on pulmonary microvascular hemodynamics in sickle red blood cell (HbSS-RBC) perfused rat lungs were studied under conditions of high and low oxygen tensions and compared with lung perfused with rat (HbRat) and normal human (HbAA) RBC controls. Independent of the RBC suspension (hematocrit 5%) used, ventilation with the room air gas mixture did not result in any significant differences in the pulmonary arterial pressure (Ppa), capillary pressure (Ppc), total pulmonary vascular resistance (RT), or angiotensin II pressor response. Ventilation of HbSS-RBC perfused lungs with a hypoxic gas mixture significantly increased the Ppa, Ppc, and RT above that which was seen in HbRat and HbAA controls. The increase in RT occurred mainly in the pulmonary artery independent of RBC suspension. In addition, no significant accumulation of lung water occurred in HbSS-RBC perfused lungs compared with HbRat and HbAA controls, as indicated by the change in capillary filtration coefficient and wet-to-dry lung weight ratio. In conclusion, deoxygenation of the HbSS-RBC and hypoxic pulmonary vasoconstriction is additive in altering pulmonary microvascular hemodynamics. PMID- 8447461 TI - Sympathetic denervation of resistance arteries increases contraction and decreases relaxation to flow. AB - The effect of chronic sympathetic and possibly sensory denervation on flow induced changes in smooth muscle tone was examined in a branch of the rabbit ear artery (200-400 microns ID). The superior cervical ganglion and 1-cm portions of the greater and anterior auricular nerves were removed from 4-wk-old rabbits while under general anesthesia, and arterial segments were studied 21 days later. Efficacy of denervation was assessed by catecholamine histochemistry and by absence of a constrictor response to transmural electrical field stimulation. Intraluminal flow of physiological saline solution was made through a pipette into matched-innervated and -denervated segments. Flow-induced contraction was increased in the denervated compared with the contralateral innervated segments. At the lowest flow rate studied (1 microliters/min), the contraction increased more than six times. This is consistent with the previously described nonspecific, nondeviational hypersensitivity of denervated vascular smooth muscle to constrictor influences. By contrast flow-related dilation at 10 and 20 microliters/min was significantly diminished. An intraluminal flow rate could be found that resulted in dilation in innervated but not the matched-denervated segments. Endothelial-mediated dilation to acetylcholine was also impaired. Chronic sympathetic denervation increased the magnitude of flow contraction and decreased that of flow relaxation. PMID- 8447462 TI - Activation of cardiac KATP channels: an endogenous protective mechanism during repetitive ischemia. AB - The role of KATP channels in myocardial stunning produced by repetitive coronary occlusions was studied in barbital-anesthetized dogs. Regional percent segment function (%SS) was measured by sonomicrometry, and the monophasic action potential (MAP) in the ischemic region was measured by an epicardial probe. Under control conditions, six 5-min periods of coronary occlusion, interspersed with 10 min periods of reperfusion, and ultimately followed by 2 h of reperfusion produced regional segment dysfunction and a similar rate and amount of shortening of the MAP measured at 50% repolarization duration (MAPD50) during each successive ischemic period. Pretreatment with glibenclamide (0.3 mg/kg iv), a KATP channel antagonist, significantly prevented the reduction of MAPD50, particularly during the first occlusion period, and it worsened postischemic dysfunction. In contrast, pretreatment with aprikalim (10 micrograms/kg bolus +/- 0.1 microgram.kg-1.min-1 iv), a KATP channel opener, accelerated the rate and extent of shortening of MAPD50 during each occlusion and markedly improved %SS throughout reperfusion. Pretreatment with d-sotalol (2 mg/kg iv), an antagonist of voltage-dependent K+ channels, significantly prolonged MAPD50 of the ischemic region before coronary occlusion but did not alter the rate of shortening of MAPD50 during ischemia and did not affect the recovery of %SS. These results indicate that activation of KATP channels during ischemia with the resultant shortening of the MAPD50 is an endogenous adaptive mechanism that affords functional myocardial protection during repetitive, brief periods of coronary arterial occlusion. PMID- 8447463 TI - Low baroreflex sensitivity predisposes to salt-sensitive hypertension in the rabbit. AB - The aim of this study was to determine the effect of an increase in dietary salt on blood pressure (BP), Na+ balance, and plasma renin activity (PRA) in normotensive rabbits bred for differences in cardiac baroreflex sensitivity (BRS). Food and fluid intake, BP, heart rate, body weight, PRA, hematocrit, and creatinine clearance were monitored weekly and Na+ balance daily for 3 wk each on normal NaCl (8 meq/day) and high salt (32 meq/day) in 27 rabbits of the second and third generation of animals bred for high BRS (group I, 6.1 +/- 0.3 beats.min 1.mmHg-1, n = 9) or low BRS (group II, 3.61 +/- 0.1 beats.min-1.mmHg-1, n = 18). BRS was assessed in each animal on normal salt and at the end of the high-salt period. Both systolic and diastolic BP rose by > 10 mmHg in 50% of group II and by < 5 mmHg in the remainder and in all group I. The rise in BP was associated with Na+ and fluid retention and weight gain during the first 2 wk, which returned to presalt levels by the 3rd wk, although BP continued to rise. The lack of effect on BP in the remaining nine group II was associated with a marked sensitization of their BRS by the high salt to 6 +/- 0.4 beats.min-1.mmHg-1. BRS remained unchanged in the other rabbits. A highly significant correlation (P < 0.001) was found between the increment of BP and BRS after 3 wk of raised salt intake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447464 TI - Endothelium dependence of effects of high PCO2 on agonist-induced contractility of rat aorta. AB - To investigate the modulation of CO2 and endothelium of vascular contraction induced by various agonists, we studied the influence of high PCO2 (PCO2 = 91 mmHg, pH = 6.99) on the response of endothelium-intact and -rubbed rat aortic preparations to KCl, phenylephrine (PE), and human-porcine endothelin-1 (ET-1). Response of endothelium-intact aortic preparations to KCl was not influenced by both high PCO2 and the pH-matched acidotic solution (7.00) with normal PCO2, whereas that of endothelium-rubbed preparations was attenuated solely by high PCO2. With cyclooxygenase inhibitors or a thromboxane A2 receptor antagonist, high PCO2 attenuated the respose of both preparations to KCl. The dose-response curve of endothelium-intact and -rubbed preparations to PE was shifted to the right by both high PCO2 and the pH-matched acidotic solution with normal PCO2. The maximal response of endothelium-intact preparation to PE was attenuated by high PCO2. Indomethacin augmented the inhibitory action of high PCO2 on the PE induced contraction. Contractile responses of endothelium-intact and -rubbed preparations to ET-1 were not influenced by high PCO2. With indomethacin, high PCO2 also had no influence on the ET-1-induced contraction of endothelium-intact preparations. Endothelium modified the high PCO2 effects on the time-contraction responses to the three agonists. CO2 and endothelium may variously modify the responses of rat aorta to different agonists. Cyclooxygenase-related eicosanoid(s) may be involved in the effects of high PCO2 on the response of rat aortic smooth muscle cells to KCl and PE. PMID- 8447465 TI - Dextran increases survival of subconfluent endothelial cells exposed to shear stress. AB - In vitro devices in combination with cultured cells have been used to study the relationship between shear stress and endothelial injury. Almost exclusively, these investigations have used confluent monolayers and conventional culture media as perfusates and reported little cell loss over a wide range of shear stress conditions. In this investigation when subconfluent endothelial cells were exposed to 22 and 88 dyn/cm2 for 2, 8, and 24 h in a perfusate of medium and 5% serum, a progressive cell loss was observed. Lower cell densities were a product of decreased cell proliferation as measured by bromodeoxyuridine (BrdU) incorporation and loss of the initial cell population. Video recordings indicated that cells characteristically detached by proximal cell peeling from the substrate and an aneurysmal rupture of the cell membrane. Cell retention was increased by including 250 and 475 microM neutral dextran (70 kDa) in perfusates. Experimental evidence suggests dextran does not directly stimulate proliferation or correct an osmotic imbalance. This investigation has substantiated that fluid generated shear stress can cause endothelial denudation and that conditions (subconfluency, time, and perfusate supplementation) under which shear stress is applied are as important for cell survival as shear stress magnitude. PMID- 8447466 TI - Changes in myocardial contraction patterns in response to regional ischemia and sympathetic nerve stimulation. AB - We studied the effect of inferior cardiac nerve stimulation on global and regional left ventricular function before and after circumflex coronary arterial (CFX) occlusion in 12 pentobarbital-anesthetized cats. Regional function was evaluated by orthogonal sonomicrometry in the anterior midwall of the left ventricle and by two-dimensional short-axis echocardiography. CFX occlusion provoked hypokinesis in the nonischemic free wall adjacent to the dyskinetic ischemic region (17.6 +/- 2.3 vs. 34.6 +/- 2.2% preocclusion wall thickening; P < 0.01) and gradually improved systolic wall thickening toward the contralateral remote region, where the maximal hyperkinetic response was measured (52.9 +/- 4.4 vs. 32.5 +/- 3.3% preocclusion wall thickening; P < 0.001). In the anterior wall, remote region, hyperkinesis was predominant in longitudinal segments (8.1 +/- 0.8 vs. 2.3 +/- 0.6% preocclusion ejection shortening; P < 0.001) and slight in circumferential segments (11.0 +/- 0.7 vs. 9.1 +/- 0.6% preocclusion ejection shortening; P < 0.01). The postocclusion systolic wall thickening and segment shortening pattern were not modified by sympathetic nerve stimulation, which increased cardiac output less after coronary occlusion, although contractility (dP/dt) increased markedly. In conclusion, the myocardial contraction pattern in ischemic and nonischemic regions after CFX occlusion is not much modified by sympathetic cardiac nerve stimulation. PMID- 8447467 TI - Effect of limb anesthesia on middle cerebral response to handgrip. AB - Transcranial Doppler ultrasound was used to measure middle cerebral arterial mean flow velocity (Vmean) on both sides of the brain in 12 subjects during hand contractions before and during regional anesthesia of the left arm. At rest Vmean was 49 (36-104) cm/s (median and range) and was unaffected by regional anesthesia. During right-hand contractions Vmean remained unchanged on the right side of the brain, whereas it increased 20 (4-37)% (P < 0.01) on the left side of the brain. Similarly, during left-hand contractions Vmean increased 24 (2-42)% (P < 0.01) on the right side of the brain, while it remained unchanged on the left side of the brain. Regional anesthesia did not quantitatively affect Vmean during right-hand contractions. In contrast, during left-hand contractions, both right and left Vmean tended to decrease. Increases in Vmean appeared despite a decrease in arterial carbon dioxide tension (P < 0.01). Heart rate and blood pressure responses to hand contractions were enhanced during regional anesthesia (P < 0.01), but left-hand contractions resulted in a less pronounced increase in blood pressure (P < 0.01). These data demonstrate a contralateral increase in cerebral perfusion during hand contractions that is dependent on intact afferent input from the working limb. PMID- 8447468 TI - Endothelial function in well-developed canine coronary collateral vessels. AB - This study examined responses of coronary collateral blood flow to endothelial dependent vasodilators. Studies were performed in 13 dogs 4-6 mo after embolic occlusion of the left anterior descending coronary artery (LAD). Collateral flow was determined as the sum of retrograde flow from the cannulated LAD, and continuing tissue flow was measured with microspheres administered during the retrograde flow collection. Agonists were introduced into the left main coronary artery to reach collaterals arising from the left coronary arterial system. The endothelial-dependent vasodilators acetylcholine and bradykinin caused 21 +/- 7 and 25 +/- 8% increases of collateral flow, respectively (each P < 0.05). This was not different from the 28 +/- 8% increase in collateral flow produced by nitroglycerin. To determine whether vasodilator prostaglandins contributed to the increased collateral flow, studies were performed after cyclooxygenase blockade with indomethacin (5 mg/kg iv). Indomethacin caused a 30 +/- 9% decrease of retrograde flow during basal conditions but did not blunt the maximum collateral flow rates produced by acetylcholine, bradykinin, or nitroglycerin. These data demonstrate intact endothelial-dependent vasodilator mechanisms in the well developed coronary collateral circulation. PMID- 8447469 TI - Cultured adult cardiac myocytes maintain protein synthetic capacity of intact adult hearts. AB - Previous studies have shown that the rates of protein synthesis observed in embryonic and neonatal heart cells in culture are as much as nine times greater than the rates of synthesis observed in the intact adult heart either in situ or in isolated perfusion studies. This study addressed whether adult cardiomyocytes in long-term culture maintain the protein synthetic capacity of the adult myocardium or, rather, whether the protein synthetic capacity expands or falls as adult cardiac myocytes progress in culture. Protein synthesis was evaluated in isolated adult feline cardiomyocytes maintained in serum and insulin-supplemented medium for up to 53 days in vitro. With the use of both pulse- and saturation labeling techniques it was determined that the rate of protein synthesis in adult cardiomyocytes was maintained at a level very close to that observed in the intact heart for over 1 mo in culture. Saturation-labeling studies indicate a fractional rate of protein synthesis at 6.1%/day and an absolute synthesis rate of 1,300 nmol leucine incorporated.g protein-1.h-1. Pulse-labeling studies revealed an initial increase in protein synthesis rates during adaptation to culture and a further increase after activation of beating and cellular hypertrophy. PMID- 8447470 TI - Different responses of the human gastroepiploic and internal mammary arteries to vasoactive peptides. AB - Peptidergic influences have been implicated in the control of tone in human arteries. We have examined the response of human gastroepiploic arteries (GEA) and internal mammary arteries (IMA) to three vasoactive peptides in vitro. Vasoactive intestinal peptide (VIP, 10(-11) to 3 x 10(-7) M) elicited relaxations in the GEA and IMA [maximum generated response (Emax) 74.6 +/- 9.4 and 56.5 +/- 7.7%, respectively] that were significantly reduced after removal of endothelium. NG-monomethyl-L-arginine (L-NMMA) and indomethacin partially inhibited the response of the GEA to VIP (P < 0.05). In the IMA, VIP-induced relaxation was significantly attenuated by L-NMMA but not indomethacin. Bombesin (10(-10) to 3 x 10(-6) M) produced endothelium-dependent relaxation selectively in the GEA, which was only inhibited by indomethacin (Emax reduced from 59.0 +/- 10.0 to 12.8 +/- 4.9%, P < 0.001). Bombesin elicited a weak endothelium-independent constriction in the IMA, giving 12.7 +/- 1.2% of the response to 90 mM KCl. Gastrin (10(-10) to 3 x 10(-7) M) had no effect on IMA segments but induced a relaxation of 40.0 +/- 3.2% in the GEA via a direct action on the smooth muscle. It is concluded that human GEA and IMA exhibit heterogenous responses to VIP, bombesin, and gastrin that may have important physiological and clinical implications. PMID- 8447471 TI - Microgravity and orthostatic intolerance: carotid hemodynamics and peripheral responses. AB - A ground-based model [24 h of bed rest (BR) with head-down tilt (HDT)] was used to investigate the cardiovascular deconditioning responsible for orthostatic intolerance, frequently observed after weightlessness flights. This experimental deconditioning is shown to be distinguished by an increase of mean blood pressure (P < 0.05), with increased total peripheral resistances (TPRs). Systolic tangential tension of the carotid arterial wall, cardiac output and frequency (spectral analysis), and plasma norepinephrine and epinephrine were not significantly altered, while plasma dopamine was increased (P < 0.05). Cardiovascular homeostasis was challenged before and after 24 h of BR with HDT through -40 mmHg lower body negative pressure (LBNP). Systolic tangential tension of the carotid wall was decreased, with a decrease of systolic pressure and cardiac output; increased heart rate was likely due to an increase of sympathetic drive with a decrease of vagal braking. The overall picture was not changed after 24 h of BR with HDT, except for a lack of increase of TPRs: their increase (+13.7%, P < 0.05) before was no longer observed after (-2.6%) 24 h of BR with HDT. This apparent deficiency cannot be explained. However, a heterogeneity in the response of TPR should be considered because the magnitude of the increase of blood pressure to cold pressor test was the same after 24 h of BR with HDT as it was before.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447472 TI - Fatty acid inhibition of angiotensin II-stimulated inositol phosphates in smooth muscle cells. AB - Inositol phosphate (InsP) responses to angiotensin II (ANG II) stimulation were measured in cultured rat vascular smooth muscle cells (VSMC) incubated with and without fatty acids (FA). VSMC were washed after 24 h of FA incubation to achieve cellular incorporation of FA yet eliminate ambient FA. Incubation with eicosapentaenoic acid (EPA)-supplemented medium resulted in concentration dependent incorporation of EPA and depletion of arachidonic acid in VSMC membranes. Incubation with EPA, but not other FA, resulted in inhibition of ANG II-stimulated InsP formation (29% inhibition with 100 microM EPA). In contrast, InsP formation in response to guanine nucleotide-binding protein stimulation was not affected by EPA. ANG II receptor binding to membranes prepared from EPA loaded VSMC was 18% lower than binding in membranes from sham-loaded cells. In other studies, VSMC were exposed acutely to FA to avoid cellular incorporation. Exposure to all FA resulted in concentration-dependent reductions in ANG II binding and ANG II-stimulated InsP formation; binding affinity was reduced without changes in receptor density. We conclude that ANG II-stimulated InsP formation is modestly and selectively inhibited by EPA incorporation and more profoundly inhibited by acute exposure to many FA via interference with ANG II receptor binding. PMID- 8447473 TI - Mesenteric lymph flow responses to splanchnic nerve stimulation in sheep. AB - The main mesenteric lymph duct was cannulated in halothane-anesthetized sheep, and continuous recordings were made of lymph flow, lymphatic pressure fluctuations, and arterial pressure. Stimulation of the left greater splanchnic nerve at frequencies of 1, 4, and 10 Hz caused lymph flow to increase by 30 +/- 9, 74 +/- 19, and 80 +/- 21%, respectively. Lymphatic contraction frequency and mean arterial pressure showed graded increases in response to increasing stimulus frequencies. These responses were reduced after intravenous infusion of phentolamine, suggesting that they were mediated by alpha-adrenoceptors. Lymph protein concentration remained unchanged during stimulation, suggesting that lymph formation in the nodes was not responsible for the increased lymph flow. The lymph flow response during 20 min of stimulation was biphasic, showing an initial transient increase followed by a depression to 45% of control. It is concluded that the initial increase in flow may be explained by stimulation of the lymphatic pump by nerves and/or circulating catecholamines, while the subsequent decrease reflected a reduction in lymph formation. PMID- 8447474 TI - Plasmin potentiates induction of nitric oxide synthesis by interleukin-1 beta in vascular smooth muscle cells. AB - Experiments were performed to examine the effect of the major fibrinolytic protease, plasmin, on the production of nitric oxide from interleukin-1 beta (IL 1 beta)-treated cultured human and rat aortic smooth muscle cells. Incubation of vascular smooth muscle cells with IL-1 beta resulted in significant accumulation of nitrite and nitrate in the culture media. Plasmin, either added exogenously or generated by the reaction of tissue plasminogen activator with plasminogen, potentiated the IL-1 beta-mediated release of nitrite and nitrate from smooth muscle cells in a concentration-dependent manner, without affecting the production of nitrite and nitrate from cells untreated with IL-1 beta. This potentiating effect was abolished when plasmin was incubated with the protease inhibitor, alpha 2-antiplasmin. The perfusates from columns containing IL-1 beta treated smooth muscle cells relaxed detector blood vessels without endothelium, and the addition of IL-1 beta-treated smooth muscle cells to suspensions of indomethacin-treated platelets inhibited their aggregation. Untreated smooth muscle cells or cells treated with plasmin alone did not have such effects. However, the simultaneous treatment of smooth muscle cells with IL-1 beta and plasmin markedly enhanced both the relaxing activities of the perfusates and the inhibition of platelet aggregation. Treatment of smooth muscle cells with NG nitro-L-arginine inhibited the cytokine-mediated effects as well as the potentiating effect of plasmin. These results demonstrate that the plasmin can enhance the production of nitric oxide by IL-1 beta-treated vascular smooth muscle cells. PMID- 8447475 TI - Floating axis does not reduce motion artifacts in a model of left ventricular wall motion in dogs. AB - Methods of measuring regional wall motion of the left ventricle superimpose end diastolic and end-systolic images. Differences in dimensions between images are assumed to be due to contraction, but they are also due to motion artifacts. To determine whether the errors caused by motion artifacts are reduced when measured with floating-axis referencing, and whether the measurement method affects these errors, we simulated end-systolic angiograms of a pure contraction (control) and contractions affected by motion artifacts and then measured differences in wall motion between angiograms with hemichord, radial, and trapezoid methods, using floating-axis and fixed-axis referencing. We chose these three methods because they form the basis for other methods, e.g., the center line method. For the simulations, we applied deformation patterns of the left ventricle, computed from the motion of tantalum markers implanted in the endocardiums of six dogs, to end diastolic angiograms. This marker method measured the myocardial wall motion directly, independent of the angiogram. We found that differences caused by motion artifacts were not significantly reduced when measured with floating-axis referencing in our model. Normalized differences measured by radial and trapezoid methods were not significantly different, but they were significantly smaller than those measured by the hemichord method. We conclude that the axis referencing system has no significant effect on errors caused by motion artifacts in regional wall motion in our model. The measurement method, however, does affect these errors, with the radial and trapezoid methods being superior to the hemichord method. PMID- 8447476 TI - Isolation and characterization of human and rat cardiac microvascular endothelial cells. AB - Although reciprocal intercellular signaling may occur between endocardial or microvascular endothelium and cardiac myocytes, suitable in vitro models have not been well characterized. In this report, we describe the isolation and primary culture of cardiac microvascular endothelial cells (CMEC) from both adult rat and human ventricular tissue. Differential uptake of fluorescently labeled acetylated low-density lipoprotein (Ac-LDL) indicated that primary isolates of rat CMEC were quite homogeneous, unlike primary isolates of human ventricular tissue, which required cell sorting based on Ac-LDL uptake to create endothelial cell-enriched primary cultures. The endothelial phenotype of both primary isolates and postsort subcultured CMEC and their microvascular origin were determined by characteristic histochemical staining for a number of endothelial cell-specific markers, by the absence of cells with fibroblast or pericyte-specific cell surface antigens, and by rapid tube formation on purified basement membrane preparations. Importantly, [3H]-thymidine uptake was increased 2.3-fold in subconfluent rat microvascular endothelial cells 3 days after coculture with adult rat ventricular myocytes because of release of an endothelial cell mitogen(s) into the extracellular matrix, resulting in a 68% increase in cell number compared with CMEC in monoculture. Thus biologically relevant cell-to-cell interactions can be modeled with this in vitro system. PMID- 8447477 TI - Endothelial cell calcium increases during flow-induced dilation in isolated arterioles. AB - The influence of flow on endothelial intracellular calcium concentration ([Ca2+]i) was determined in intact, isolated arterioles by selectively loading endothelial cells with the calcium-sensitive fluorescent dye fura-2. A fluorescence microscope coupled to a digital image processor was used to simultaneously measure fura-2 fluorescence and microvessel diameter. Flow through the arteriole significantly increased endothelial [Ca2+]i and dilated arterioles. Acetylcholine also increased in endothelial [Ca2+]i and caused vasodilation. In comparison, adenosine did not alter endothelial [Ca2+]i but dilated arterioles. Removal of the endothelium abolished the responses to flow and acetylcholine but not adenosine. These results provide strong support for the involvement of calcium in endothelium-dependent dilation of isolated arterioles by flow and agonists and emphasize the importance of studying endothelial function in intact vessels. PMID- 8447479 TI - Muscle: the predominant glucose-producing organ in the leopard frog during exercise. AB - Although liver is thought to be the major glucose-producing organ in vertebrates, it is not the major source responsible for the accumulation of glucose in frogs during burst activity. This is indicated by the absence of significant changes in liver glycogen levels during exercise, the inability of the maximal reported rate of hepatic glucose production in vitro to account for the increase in the glucose content of the frog, and from the observation that hepatectomized and normal frogs accumulate similar amounts of glucose in their muscles and body during exercise. We conclude that most glucose that accumulates in the body during exercise originates in muscle because two-thirds of body glucose is found in muscle and because the intracellular levels of muscle glucose rise well above plasma levels. The glucose that accumulates outside muscle is also likely to originate in muscle. The most likely metabolic source of the glucose produced by muscle is the glycogen hydrolyzed by amylo-1,6-glucosidase. PMID- 8447478 TI - Independence of heart rate and circadian period in the golden hamster. AB - Cardiac contractions are under the influence of at least two processes of biological timing, one responsible for the mean level of heart rate (oscillations with a frequency of up to several hundred per minute) and another responsible for the circadian rhythm of heart rate (oscillations with a frequency of one per 24 h). To investigate whether the mean level of heart rate is proportional to the frequency of circadian oscillation, we compared the heart rates of normal golden hamsters (circadian period approximately 24 h) and tau-mutant hamsters (circadian period approximately 20 h). Neither in anesthetized preparations nor in freely moving animals was there a difference in heart rate between the two groups despite the 20% difference in circadian period. Thus the mean level of heart rate seems to be independent of the circadian period. It is likely that the tau gene, which affects the frequency of the circadian pacemaker, has no effect on the intrinsic frequency of the cardiac pacemaker. In vitro studies of isolated hearts or myocardial cell cultures are necessary to confirm this inference. PMID- 8447480 TI - CCK satiety is differentially mediated by high- and low-affinity CCK receptors in mice and rats. AB - Cholecystokinin-JMV-180 (JMV-180) is an analogue of cholecystokinin C-terminal octapeptide (CCK-8), which has been shown to be an agonist at the proposed CCK pancreatic high-affinity site and a functional antagonist at the pancreatic low affinity site in rats and to have agonist activity at both high- and low-affinity sites in the mouse. In this study we used JMV-180 to evaluate the potential participation of these two CCK-A sites in the satiety effect of CCK-8 in rats and mice. When tested at doses that ranged from 0.01 to 9.2 mumol/kg, JMV-180 did not reliably affect food intake of solid or liquid test diets in rats. When combined with CCK-8 (3.2 or 8.5 nmol/kg) JMV-180 dose dependently reversed the satiety effect of CCK-8. In contrast to these results in the rat, both JMV-180 (3.7-14.8 mumol/kg) and CCK-8 (1.7-6.8 nmol/kg) dose dependently reduced the intake of 20% sucrose in mice. Both CCK-8- and JMV-180-induced suppression of food intake were attenuated by the CCK-A antagonist MK-329 (24.8 nmol/kg). The results of these studies suggest that agonist activity at sites pharmacologically similar to the CCK pancreatic high-affinity site is not sufficient for expression of CCK satiety, whereas agonist activity at low-affinity-like sites is necessary to reduce food intake. Thus the anorexic activity of CCK appears to be mediated through an interaction with a receptor site pharmacologically similar to the pancreatic low-affinity CCK receptor site. PMID- 8447481 TI - Brain sensitivity to anoxia in fish as reflected by changes in extracellular K+ activity. AB - Most vertebrates have a very limited tolerance to anoxia. The only exceptions to this rule are found among ectothermic species, notably crucian carp (Carassius carassius) and freshwater turtles. It has been assumed that the brains of these species are less sensitive to anoxia than ectothermic brains in general. However, it has not been possible to exclude that anoxia-intolerant species like rainbow trout (Oncorhynchus mykiss) die from heart failure rather than brain failure during anoxia, and that the average ectothermic brain is actually rather insensitive to anoxia. By simultaneously measuring the effect of anoxia on brain extracellular K+ activity ([K+]o), blood pressure, and heart rate in rainbow trout, we show that the rainbow trout brain rapidly loses ion homeostasis during anoxia, despite an initial increase in blood pressure. The rainbow trout brain showed a sudden transient increase in [K+]o (suggesting a rapid depolarization) after approximately 30 min of anoxia at 10 degrees C. At the same time the blood pressure was still close to the normoxic value. In a comparative experiment, crucian carp was found to maintain a low brain [K+]o for at least 6 h of anoxia. Thus the results suggest that the rainbow trout brain is anoxia-intolerant in itself, and that its ability to maintain ion gradients during anoxia is very much lower than that of crucian carp. If temperature differences are taken into account, the anoxia sensitivity of the rainbow trout brain is comparable to that of mammals. PMID- 8447482 TI - Autonomic regulation of heart rate and blood pressure in hemorrhaged toads. AB - Mean arterial blood pressure (P(a)) and heart rate (HR) were studied in normal conscious cane toads (Bufo marinus) or in autonomically blocked animals treated variously with bretylium, atropine, phentolamine, and propranolol. Partial or total autonomic blockade had no effect on resting values of the variables tested, with the exception that atropine treatment of bretylium-treated toads caused an increase of heart rate by 5.3 +/- 1.3 beats/min. In graded hemorrhage, aliquots of blood (1.68 ml/100 g body wt) were removed at 60-min intervals. There was extensive plasma recruitment, and blood could be removed up to 10.08 ml/100 g without inducing cardiovascular shock. Each hemorrhage caused an initial transient decrease in P(a) and increase in HR followed by recovery toward prehemorrhage values. Repeated hemorrhage caused a progressive rise in basal HR and fall in basal P(a). The effects of drug treatments suggest that transient increases in HR may be caused by the release of adrenal catecholamines. In addition, hemorrhage may increase sympathetic tone so that basal HR becomes elevated, which, together with sympathetic vasoconstriction, limits the progressive fall of basal P(a). PMID- 8447483 TI - A natriuretic factor is released by saline infusion into rat renal artery. AB - Saline (154 mM NaCl) infused into one renal artery of anesthetized rats produced a prompt and substantial increase in sodium excretion without significant alteration of arterial pressure, renal blood flow, or glomerular filtration rate. A 1-h infusion at rates of 0.0375, 0.05, or 0.1 ml/min increased sodium excretion by the infused kidney from 0.15 +/- 0.04 to 0.70 +/- 0.12, from 0.45 +/- 0.10 to 2.17 +/- 0.40, and from 0.27 +/- 0.06 to 4.29 +/- 0.80 mumol/min, respectively. Natriuresis also occurred in the contralateral kidney. No comparable responses resulted from infusions at 0.0375 ml/min into the jugular vein, inferior vena cava, or carotid artery. Cross-circulation of blood from infused rats increased sodium excretion in uninfused recipients from 0.36 +/- 0.11 to 1.43 +/- 0.43 mumol.min-1.kidney-1. Isovolemic exchange-transfusion of blood from infused donor rats increased sodium excretion in uninfused recipients from 0.30 +/- 0.05 to 0.51 +/- 0.09 mumol.min-1.kidney-1. In both experiments, aortic infusions below the renal artery produced no comparable effect in recipient rats. Infusion of 300 mM glucose was not natriuretic. Infusion of two NaCl loads, 5.8 and 15.4 mumol/min, each at two different rates, increased sodium excretion in proportion to the load of NaCl and not to the rate of infusion. Infusions of a protein-free artificial rat plasma or of 140 mM NaCl, both with the sodium concentration of rat plasma, produced very little increase in sodium excretion. Infusion of 154 mM sodium lactate produced an increase in sodium excretion comparable to that produced by 154 mM NaCl. Reducing the infusion rate of 154 mM NaCl from 0.05 to 0.01 ml/min produced a rapid decline in the rate of sodium excretion. We conclude that renal arterial saline infusion activates a mechanism that increases sodium excretion by the infused kidney and concurrently causes the release of a natriuretic factor. Increased sodium concentration in renal arterial blood was the only stimulus found to produce the effect. PMID- 8447484 TI - Evaluation of renal hormones in natriuresis induced by renal arterial saline infusion. AB - Low rates of unilateral renal arterial infusion with isotonic saline (154 mM NaCl) produce a natriuresis in both kidneys in anesthetized rats, with the involvement of a blood-borne factor. We investigated whether this response was modulated by known renal or adrenal hormones. The response to saline infusion at 0.05 ml/min was tested after acute adrenalectomy (n = 7), in the presence of various blocking agents [captopril (3 mg.kg-1.h-1, n = 7), indomethacin (5 mg/kg, n = 8), aprotinin (25 KIU/min, n = 8), propranolol (1 micrograms/min, n = 6), or benserazide (15 micrograms/min, n = 6)], and after lignocaine infusion around the renal artery (12.5 micrograms/min, n = 5). In all cases, the overall increase in sodium excretion by both kidneys was not significantly less (alpha < or = 0.01) than that in untreated rats; it was increased by aprotinin, renal nerve blockade, and propranolol. Plasma levels of angiotensin II, aldosterone, and atrial natriuretic peptide were unchanged by renal arterial saline infusion. We conclude that the saline-induced natriuresis is not reduced by inhibition of the production of angiotensin II, prostaglandins, kinins, dopamine, or adrenal hormones, or by factors released by the renal nerves, indicating that none of these is directly responsible for the saline-induced natriuresis. PMID- 8447485 TI - High NaCl intake of rat dams alters maternal behavior and elevates blood pressure of adult offspring. AB - The present study investigated whether differences in maternal NaCl intake altered 1) maternal-pup behavior and 2) the development of dietary obesity and blood pressure level of adult Sprague-Dawley rats maintained on a palatable high fat/milk (HF/M) diet. Thirteen dams fed high (3%) NaCl and 12 dams fed basal (0.12%) NaCl were observed on postnatal days 2-21 for differences in the number of times spent 1) nursing, 2) in contact with or licking, sniffing, and carrying pups, and 3) in nest building. The offspring were continued on their respective NaCl diets to 30 days postpartum, and then both NaCl groups were fed an intermediate (1%) NaCl diet thereafter. Beginning at 60 days of age, the offspring from each maternal NaCl condition were fed either Agway R-M-H 1000 pelleted food or a HF/M diet for 14 wk. Dams fed 3% NaCl spent significantly more time licking their pups than did dams fed 0.12% NaCl. The adult offspring of dams fed 3% NaCl had a significantly higher level of systolic blood pressure and consumed more calories of sweetened condensed milk on the HF/M diet than did rats raised on 0.12% NaCl. Dietary-induced obesity did not magnify the increase in systolic blood pressure from high maternal NaCl intake. The present results raise the possibility that increased maternal licking may contribute to the increased blood pressure and solution intake that follows from high maternal NaCl intake. PMID- 8447486 TI - Lick rate analysis of sodium taste-state combinations. AB - The combined effects of taste and physiological state on lick rate for NaCl were systematically evaluated in two experiments. In experiment 1 the lick rates of six groups of rats (Sprague-Dawley) were recorded during the first 3 min of a NaCl drinking bout, where each group received a different concentration. Half of the rats were depleted by injections of the diuretic-natriuretic furosemide (10 mg ip), whereas the other half were not. The inverted U-shaped concentration response functions for sodium-replete rats peaked approximately at isotonicity. The replete lick rate function was uniformly elevated for rats examined in the sodium-depleted state. In experiment 2 each rat received access to all six solutions within a 40-min test session. Rats were tested twice, once in positive and once in negative sodium balance. The solutions were repeatedly presented in counterbalanced order in a series of 10-s exposures. The replete and deplete functions of the within-group study closely resembled those of the between-group study. When the deplete rats' function was divided into three segments coinciding with the beginning, middle, and end of the 40-min session, the functions were shifted down vertically but retained their shape. In general, sodium-state level dramatically affected the absolute lick rates but did not appear to shift the location of the concentration-response function along the horizontal (i.e., concentration) axis. The form of the function appears to have been determined by oral factors alone. PMID- 8447487 TI - Chorda tympani section decreases the cation specificity of depletion-induced sodium appetite in rats. AB - Rats depleted of sodium by diuretic treatment were tested for their ability to respond selectively to NaCl after chorda tympani nerve (CTn) section (CTX). A variety of chloride salts (NaCl, KCl, NH4Cl, CaCl2) at two concentrations (0.05 and 0.3 M) were presented semirandomly to sodium-deplete rats in repeated single stimulus trials (10 s). The responses of sodium-depleted surgical control rats (n = 8) were highly cation specific. These rats licked substantially more for both sodium stimuli than for any other chloride salt. On the other hand, the licking responses of CTX sodium-depleted rats (n = 8) were less cation selective. These rats licked NaCl and 0.05 M KCl at comparable rates. For both NaCl concentrations, CTX rats had significantly lower lick rates than controls. In addition, the difference between the lick rate for NaCl and that for the other salts was much greater for control rats than for CTX rats. Although CTn section did not entirely eliminate the high levels of responsivity to NaCl observed in the intact sodium-depleted rat, it did substantially compromise the selectivity of the behavior, which suggests that the input of the CTn is critical for taste guided sodium specific behaviors. PMID- 8447488 TI - GABAergic effects on respiratory neuronal discharge during opossum development. AB - Changes in breathing pattern between immature and adult animals could be due in part to changing postsynaptic sensitivity to particular neurotransmitters by respiratory neurons and/or to the fate of these neurotransmitters after release. To probe for such effects, gamma-aminobutyric acid (GABA) and the GABAA antagonist, bicuculline, were pressure injected by micropipette in very small volumes (approximately 25 pl) near identified medullary respiratory neurons in Inactin-anesthetized adult and suckling opossums. At a concentration of 10 mM, GABA induced suppression of respiratory neurons firing in animals from about 3 wk of age (the youngest animals tested) onward, with the largest responses occurring in adults. For those age groups tested with 0.5 and 50 mM GABA, shorter and longer responses, respectively, were observed. Bicuculline increased the discharge of respiratory units at all ages tested, but responses normalized to initial firing rates did not systematically differ between sucklings down to 4 wk of age and adults. Bicuculline also influenced the onset and cessation of firing in both inspiratory and expiratory neurons. Discharge of respiratory neurons in immature suckling opossums is characterized by few spikes and low firing rates with each breath. However, recovery of neuronal firing from an exogenous load of GABA and release of neuronal firing after antagonism of GABAA receptors does not show a developmental pattern that would implicate GABA as the crucial mediator of these effects. PMID- 8447489 TI - Regulation of renal hemodynamics after protein feeding: effects of proximal and distal diuretics. AB - The purpose of these studies was to compare the effects of proximally and distally acting diuretics on the renal hemodynamic response to protein feeding to determine the importance of the proximal tubule in postprandial renal vasodilation. In chronically instrumented conscious dogs, a meat meal (10 g/kg raw beef) caused glomerular filtration rate (GFR) to increase from 63 +/- 5 to 87 +/- 10 ml/min and effective renal plasma flow (ERPF) to increase from 189 +/- 20 to 249 +/- 20 ml/min, while plasma alpha-amino nitrogen levels rose from 4.0 +/- 0.1 to 6.8 +/- 0.4 mg/dl. Administration of amiloride (0.2 mg/kg + 0.003 mg.kg 1.min-1) or potassium canrenoate (1.76 mg/kg + 1.76 mg.kg-1.h-1), diuretics that act in the distal tubule, had no effect on the renal hemodynamic responses to a meat meal. However, the normal renal hemodynamic responses to protein feeding were abolished during administration of a diuretic that acts in the proximal tubule, acetazolamide (20 mg/kg + 20 mg.kg-1.h-1), although plasma alpha-amino nitrogen levels increased after the meat meal in all experiments. These data suggest that normal proximal tubular sodium reabsorptive function is necessary for acute protein-stimulated renal vasodilation and are consistent with the hypothesis that a tubuloglomerular feedback mechanism may mediate postprandial renal vasodilation. PMID- 8447490 TI - Baroreflex buffering of pressor response to vasopressin is mediated by V1, not V2, receptors in conscious rats. AB - Arginine vasopressin (AVP) enhances reflex buffering of its own pressor response, thus attenuating its vasoconstrictor potential in vivo. To investigate the extent to which this effect of AVP is mediated by V1 or V2 receptors, mean arterial pressure (MAP) and heart rate (HR) changes were examined in response to graded injections of AVP or [Phe2,Orn8]oxytocin, a potent, selective V1-receptor agonist, in the absence and presence of infusion of [Val4,D-Arg8]VP, a selective V2-receptor agonist. Responses were compared in intact and autonomically blocked conscious rats. During autonomic blockade with methscopolamine and hexamethonium, the pressor sensitivities to AVP and [Phe2,Orn8]oxytocin were similarly increased. Infusion of the V2-receptor agonist had no effect by itself on MAP or HR in conscious intact rats. It also did not alter the pressor responses to the V1 agonist, in either intact or autonomically blocked rats. In the presence of the V2 agonist, the decrease in heart rate induced by the V1 agonist was enhanced. These results indicate that reflex buffering of the pressor response to AVP in the conscious rat is mediated by V1 and not V2 receptors. However, V2 receptors may be involved in modulating the heart rate response to AVP. PMID- 8447491 TI - Intravenous infusion of bombesin reduces food intake in humans. AB - Infusion of bombesin into healthy young men at two dosages (1.33 and 4.0 ng.kg 1.min-1) resulted in a significant 135-g reduction in intake of a yogurt and fruit blend, compared with saline infusions, at the higher dose, but only a 20-g (nonsignificant) reduction at the lower dose. There were no overt side effects, although half of the subjects reported a slightly elevated (mean elevation = 0.5 on a 1-5 category scale) sick sensation when receiving bombesin at the higher dose, but not when receiving saline. At the higher dose, the mean palatability of the test meal was reduced by 0.5 units on a nine-point scale of liking. This study demonstrates for the first time in humans that a slow intravenous infusion of bombesin can decrease spontaneous food intake when infused at the rate of 4 ng.kg-1.min-1 beginning at the onset of a meal. These results confirm that the short-term satiety effect of peripherally administered bombesin previously reported in animals can be obtained in humans. PMID- 8447492 TI - Cardiac-renal-neural reflex plays a major role in natriuresis induced by left atrial distension. AB - The role of cardiac-renal-neural reflex in the natriuresis induced by left atrial balloon inflation was investigated in conscious dogs. Female mongrel dogs were assigned randomly to 1) sham-operated (n = 8), 2) cardiac-denervated (n = 6), and 3) renal-denervated (n = 8) groups. The dogs were chronically instrumented with a bipolar stainless steel wire electrode for measurement of renal sympathetic nerve activity (RSNA). Balloon inflation induced a step increase in left atrial pressure (Pla) by 7.7 +/- 1.7 mmHg, a step decrease in RSNA (-66.6 +/- 5.5%), and concomitant increases in urine flow (441 +/- 142%), osmolal excretion (60 +/- 12%), and sodium excretion (300 +/- 69%) in sham-operated dogs. Renal denervation abolished the diuresis and natriuresis during balloon inflation. Chronic cardiac denervation abolished also the diuresis and natriuresis in the face of a similar increase in Pla. RSNA did not change significantly throughout the experimental period in cardiac-denervated dogs. It is concluded that a sustained reduction of RSNA originating from left atrial mechanoreceptors plays a major role in the natriuresis during left atrial distension in conscious dogs. PMID- 8447493 TI - Nutritional and metabolic adaptations to prolonged sleep deprivation in the rat. AB - To understand how and why sleep deprivation is physically harmful, we explored the possible causal relationship between its two main effects, 1) negative energy balance and 2) a composite of symptoms that resemble protein malnutrition, both of which occur despite increased food consumption. We provided balanced diets augmented with either protein or calories (by increased fat content) to freely moving rats. Interactions between sleep deprivation symptoms and energy and protein supplies were assessed from measurements of body weight regulation, consumption of macronutrients, clinical chemistry and hematology profiles, and physical appearance. The results indicate that sleep deprivation causes malnutrition, which is secondary to increased energy expenditure. Even though food consumption remained normal in sleep-deprived rats fed a diet of high protein-to-calorie ratio, body weight loss was more than 16% of baseline, development of skin lesions was hastened, and longevity was shortened by 40% compared with sleep-deprived rats fed the calorie-augmented diet. Food consumption of the calorie-fed rats was lower during baseline than that of the protein-fed group but during sleep deprivation increased to amounts 250% of normal without net body weight gain. Despite a fat-laden diet the calorie-fed hyperphagic group did not have abnormal levels of plasma cholesterol, triglycerides, or glucose, indicating accelerated turnover of nutrients. As would be consistent with calorie malnutrition, pronounced clinical chemistry or hematological abnormalities were not found in any group. Beneficial effects of the calorie-augmented diet are attributed to 1) caloric density of fat, 2) induction of hyperphagia, and 3) efficiency of utilization of fat. We conclude that diet composition interacts strongly with sleep deprivation, affecting the time course and development of pathologies, whereas it exerted negligible influence on body weight regulation under normal conditions. PMID- 8447495 TI - Hemodynamic changes induced by low blood oxygen affinity in dogs. AB - Increased tissue oxygen delivery may play a role in the increased vascular resistance that develops in volume-expanded hypertension. This hypothesis was tested by decreasing the affinity of hemoglobin for oxygen in dogs to increase unloading of oxygen to the tissues. Six chronically instrumented dogs were studied before and for 7 days after partial exchange transfusion with red blood cells modified by incorporation of inositol hexaphosphate, which, 1 h after exchange, increased the PO2 value at which hemoglobin is half-saturated with oxygen (P50) to 38.8 +/- 2.1 mmHg from a control value of 31 +/- 1.5 mmHg. Cardiac output (electromagnetic flowmeter) fell to 92.5 +/- 7.4 ml.kg-1.min-1 after 2-4 h from control values between 120.2 +/- 5.7 and 125.8 +/- 4.6 ml.kg 1.min-1. One day later, cardiac output was still significantly decreased to 104.0 +/- 5.9 ml.kg-1.min-1. As P50 returned to control over the next few days, so did cardiac output. Two to four hours after exchange, total peripheral resistance was increased to 1,144 +/- 73 mmHg.l-1.kg.min from control values between 762 +/- 26 and 790 +/- 32 mmHg.l-1.kg.min. It was still increased to 993 +/- 51 mmHg.l 1.kg.min after 1 day. Oxygen consumption did not change significantly. Cardiac output and peripheral resistance changes were significantly different from those measured in a control group of six dogs receiving exchange transfusion with sham shifted red blood cells without significant P50 changes. These results suggest that an increase in tissue oxygen delivery can raise total peripheral resistance in dogs in the absence of primary changes in fluid volumes, blood flow, or blood pressure. PMID- 8447494 TI - Ventrolateral medulla in spontaneously hypertensive rats: role of angiotensin II. AB - We investigated whether angiotensin II (ANG II), endogenous to the ventrolateral medulla (VLM), contributes to cardiovascular regulation in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. The action of ANG II endogenous to the VLM was examined by microinjection of 100 pmol of [Sar1,Thr8]ANG II into either the rostral (R) or caudal (C) VLM. This ANG II antagonist caused depressor and bradycardic responses in the RVLM and pressor and tachycardic responses in the CVLM. The magnitude of the blood pressure responses was significantly greater (P < 0.01 in RVLM and P < 0.05 in CVLM) in SHRs (-27 +/ 3 mmHg in RVLM and 29 +/- 4 mmHg in CVLM) than in WKY rats (-17 +/- 1 and 17 +/- 2 mmHg, respectively). Suppression of tonic activity of RVLM neurons by bilateral injection of muscimol in the RVLM showed that the pressor response produced by ANG II antagonist injection in the CVLM required the integrity of rostral pressor neurons. The present data suggest that ANG II endogenous to RVLM and CVLM acts as a tonic excitatory agent on vasomotor neurons of the VLM. The contribution of ANG II in the RVLM and CVLM to the prevailing level of blood pressure was significantly (P < 0.01) larger in SHRs vs. WKY rats when the effect of ANG II blockade was measured as the change in blood pressure. Blockade of gamma aminobutyric acid (GABA)A receptors in the RVLM showed that inhibitory GABAergic input to the RVLM was not diminished in this strain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447496 TI - Is arterial pressure a determinant of renal prostaglandin release? AB - The effect of changes in renal perfusion pressure (RPP) on renal prostaglandin (PG) release was investigated in conscious dogs (n = 10). PGE2, PGF2 alpha, and 6 keto-PGF1 alpha levels in renal venous and aortic plasma were measured in response to controlled reductions of RPP by an inflatable cuff implanted around the renal artery. PG plasma concentrations were determined by gas chromatography negative ion chemical ionization mass spectrometry. At control RPP, PGE2 and PGF2 alpha concentrations in renal venous plasma were severalfold higher than in aortic plasma (PGE2, 54.2 +/- 13.4 vs. 9.3 +/- 2.7 pg/ml, P < 0.01; PGF2 alpha, 40.3 +/- 10.4 vs. 10.4 +/- 3.4 pg/ml, P < 0.01), whereas only a small secretion rate was found for 6-keto-PGF1 alpha (renal vein, 24.3 +/- 2.6 pg/ml; aorta, 17.4 +/- 3.4 pg/ml; P < 0.01). Concentrations of all three PGs in renal venous or aortic plasma did not change in response to reductions of RPP within the normal range of renal blood flow (RBF) autoregulation. The mean difference between PG release at a RPP of 70 mmHg and control was for PGE2 -7.9 pg/ml with a 95% confidence interval (CI) from -20.7 to + 5.0 pg/ml; for PGF2 alpha it was -13.7 pg/ml (95% CI -29.4 to +2.0 pg/ml); and for 6-keto-PGF1 alpha it was -0.9 pg/ml (95% CI -6.0 to +4.1 pg/ml). Reductions of RPP below the lower limit of RBF autoregulation (< 66 mmHg) had no effect on 6-keto-PGF1 alpha secretion rate but decreased secretion rates of PGE2 and PGF2 alpha (n = 4).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447497 TI - Intravenous triglycerides fail to elicit satiety in sham-feeding rats. AB - The satiating effect of intravenous fat infusions was investigated in sham feeding rats. Intralipid infusions at loads of 2.5-10.0 kcal were administered into either the inferior vena cava or the hepatic-portal vein during sham feeding. Intravenous infusions of Intralipid by either route had no effect on sham feeding during 60-min tests. In earlier work we found that duodenal infusions of Intralipid rapidly inhibited sham feeding and elicited behaviours typical of satiety under test conditions identical to those of the present study. The lack of effect of intravenous infusions of Intralipid on sham feeding is further evidence for a preabsorptive site of action for the satiety effect of Intralipid. PMID- 8447498 TI - Chronic angiotensin-converting-enzyme inhibition improves cardiac output and fluid balance during heart failure. AB - The purpose of this study was to examine the sequential changes in renal and cardiovascular function produced by chronic Benazepril administration at different stages of heart failure in dogs. Heart failure was produced by rapid ventricular pacing in five dogs with a normally functioning renin-angiotensin system (angiotensin normal, AN) and six dogs chronically administered the angiotensin-converting-enzyme inhibitor (ACEI) Benazepril. After 7 days of pacing, cardiac output was significantly higher and total peripheral resistance (TPR) lower in the ACEI compared with the AN dogs. Cumulative sodium and water balance increased significantly in both groups, but after 7 days of pacing there were no significant differences between groups. However, the rate of increase in sodium and water balance was significantly less in the ACEI group. Effective renal plasma flow decreased in the AN and ACEI groups during pacing, but there were no between-group differences, and no significant changes in glomerular filtration rate (GFR) occurred in either group. In the AN dogs, pacing was continued for 7-21 days until the onset of decompensated heart failure. Urinary sodium excretion increased on the first day of ACEI infusion during this stage but returned to pre-ACEI levels during the next 2-3 days. No significant improvement in cardiac output was measured during ACEI in decompensated heart failure. These data suggest that chronic ACEI administration can improve renal and cardiac function in early heart failure without impairing GFR but is less chronic ACEI administration can improve renal and cardiac function in early heart failure without impairing GFR but is less effective in later, decompensated stages. PMID- 8447499 TI - Nonuniform regional sympathetic nerve responses to hyperinsulinemia in rats. AB - The insulin hypothesis of hypertension proposes that hyperinsulinemia increases sympathetic nerve activity (SNA) and raises arterial pressure. The goals of this study were 1) to determine if hyperinsulinemia produces regionally uniform or nonuniform increases in SNA and 2) to test the hypothesis that spontaneously hypertensive rats (SHR) have exaggerated sympathoadrenal responses to hyperinsulinemia. We measured plasma insulin, blood glucose, mean arterial pressure, and adrenal, renal, and lumbar SNA in alpha-chloralose-anesthetized SHR and normotensive Wistar-Kyoto (WKY) rats before and during infusion of two doses of insulin for 60 min each while maintaining euglycemia. In WKY rats, graded increases in plasma insulin from 27 +/- 5 (SE) to 200 +/- 29 microU/ml increased lumbar SNA from 100% to 285 +/- 26% but failed to significantly increase adrenal or renal SNA. In SHR rats, similar increases in plasma insulin from 27 +/- 4 to 213 +/- 33 microU/ml caused significant increases in adrenal (100% to 174 +/- 16%) and lumbar (100% to 307 +/- 26%) SNA but not in renal SNA. Despite increases in SNA, mean arterial pressure did not increase significantly in either group of rats. We conclude that 1) hyperinsulinemic euglycemic clamp produces regionally nonuniform increases in sympathetic nerve activity, and 2) there is a potentiated increase in adrenal SNA in SHR compared with WKY rats during hyperinsulinemia, whereas lumbar SNA responses were similar in the two strains, and renal SNA did not increase in either strain. PMID- 8447500 TI - Response of the avian kidney to acute changes in arterial perfusion pressure and portal blood supply. AB - Domestic fowl kidneys autoregulate total renal blood flow and glomerular filtration rate (GFR) over a wide range of renal arterial perfusion pressure (RAPP). Sustained (approximately 2-4 h) restriction of renal portal blood flow attenuates the autoregulatory responses. The present study was designed to assess the effects of acute (approximately 10 min) alterations of renal portal blood flow on renal function, and to dissociate the renal responses to altered renal portal blood flow from the renal responses to reductions in RAPP. The thermal pulse decay (TPD) technique and p-aminohippuric acid clearance (CPAH) were used to measure blood flow. During acute increases and decreases in renal portal blood flow, regional renal blood flow as measured by the TPD system (RBFTPD) was significantly positively correlated with total kidney blood flow represented by CPAH (RBFPAH). These results indicate that changes in total kidney blood flow induced by alteration of portal perfusion were reflected in the regional measurement of renal blood flow. Changes in renal portal blood flow did not affect the urine flow rate (UFR), GFR, or fractional excretion of sodium (FENa). Reducing RAPP from 120 to 50 mmHg significantly reduced UFR, GFR, and FENa. Overall, these results indicate that large acute changes in renal portal blood flow can significantly alter total renal blood flow without significantly affecting parameters (UFR, GFR, and FENa) primarily influenced by the renal arterial vasculature. PMID- 8447501 TI - Microcirculatory effects of hypoxic and hypercapnic vasoconstriction in frog skin. AB - The effects in frog (albino Xenopus laevis) skin of hypoxic and hypercapnic vasoconstriction on the following microcirculatory parameters were determined: capillary red blood cell flux, capillary red blood cell velocity, perfused capillary density, lineal red blood cell density, and the temporal heterogeneity of capillary red blood cell velocities. All of these parameters affect the gas exchange characteristics of respiratory organs. Measurements were made by fluorescent video microscopy of a 1.5-cm2 region of skin exposed to different gas mixtures (air, O2, N2, 5% CO2-95% air, 5% CO2-95% N2). N2 caused red blood cell flux and velocity to fall to 52 +/- 10% (P < 0.05) and 47 +/- 10% (P < 0.01), respectively, of those values during air exposure. Five percent CO2 caused capillary red blood cell flux and velocity to decrease by 51 +/- 11% (P < 0.05) and 43 +/- 11% (P < 0.01), respectively. Fluxes (P < 0.01) and velocities (P < 0.01) were also less with 5% CO2-95% N2 than with air. There were no significant differences in flux and velocity between N2, 5% CO2-95% air and 5% CO2-95% N2 (P > 0.1). There was no significant difference in flux or in velocity between O2 and air (P > 0.1). Gas composition had no significant effect on lineal red blood cell density (P > 0.35) or the density of perfused capillaries (P > 0.22). The heterogeneity of cell velocities was significantly greater with N2 than with the other gases (P < 0.01). There was no significant difference in red blood cell velocity heterogeneity between the other gases (P > 0.1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447502 TI - Temperature sensitivity of neurons in slices of the rat PO/AH hypothalamic area: effect of calcium. AB - The temperature sensitivity of spontaneously active neurons in slices of the preoptic and anterior hypothalamic areas (PO/AH) of rats was assessed by extracellular recording during sinoidal temperature displacements. Classifying cells according to their temperature coefficients (TC, impulses.s-1.degree C-1) revealed that 48% of the 177 cells tested were warm sensitive, 5% were cold sensitive, and 47% were temperature insensitive. Increasing the calcium concentration ([Ca2+]) of the artificial cerebrospinal fluid (aCSF) from 0.9 to 1.5 mM Ca2+ decreased the firing rate (FR) and TC of PO/AH neurons. Decreasing extracellular [Ca2+], however, elicited concentration-dependent increases in both parameters. This means in physiological terms that the number and temperature sensitivity of PO/AH neurons is strongly dependent on the extracellular [Ca2+]. Furthermore, these results suggest that caution is warranted when comparing numbers and temperature sensitivities of PO/AH neurons. After blocking synaptic transmission by superfusing the slice with aCSF containing reduced [Ca2+] and elevated [Mg2+], 8 out of 35 neurons ceased their spontaneous activity within 6 min, and 27 remained spontaneously active in low [Ca2+]-high [Mg2+] solution, but displayed unstable spontaneous activity and temperature sensitivity. It is concluded that aCSF with reduced [Ca2+] and elevated [Mg2+] is not a suitable tool to discriminate between inherent and synaptically mediated thermosensitivity. PMID- 8447503 TI - Cortical spreading depression blocks prostaglandin E1 and endotoxin fever in rats. AB - We have tested the hypothesis that the cortex may play a role in the development of fever. Male Sprague-Dawley rats equipped with AM transmitters for telemetric measurement of body temperature were given intracerebroventricular prostaglandin E1 (PGE1), corticotropin-releasing hormone (CRH), or intravenous E. coli endotoxin. Application of cotton pellets soaked with 3.3 M KCl to the frontal cortex (to induce spreading depression) significantly reduced fevers to PGE1 and endotoxin when compared with fever magnitude with 0.9% NaCl application to the cortex. Neither CRH-induced hyperthermia nor normal body temperatures were altered by the spreading depression. Our results reveal a novel action of spreading depression on thermoregulatory function and indicate cortical involvement in the development of fever. PMID- 8447504 TI - Evidence for a novel angiotensin II receptor involved in angiogenesis in chick embryo chorioallantoic membrane. AB - Angiotensin II acts as a growth factor in the cardiovascular system and has been implicated in angiogenesis. The existence of at least two types of angiotensin II receptors, the AT1 and the AT2 receptors, has been suggested by ligand binding studies. We used three different AT receptor antagonists to study the receptor mediating angiotensin II-induced angiogenesis in the chorioallantoic membrane (CAM) of the chick embryo. Angiotensin II caused pronounced angiogenesis of pre- and postcapillary vessels of 30-40%. This response could only be blocked by adding the peptidergic AT2 antagonist CGP-42112A. The nonpeptidergic AT2 antagonist PD123319 and AT1 antagonist losartan (DuP 753) were not effective. In addition, we used radioligand binding studies with a range of ligands to define the nature of the receptor. Our results show a high density of specific single class AT receptor with a total number of binding sites of 1,190 fmol/mg protein and an affinity constant for angiotensin II of 2.7 nM. The inhibitory concentrations (IC50) for CGP-42112A, PD 123319 and losartan were 724, > 100,000, and 59,000 nM, respectively. Our studies suggest that these binding sites act as receptors for angiotensin II-induced angiogenesis. Both functional and radioligand binding studies suggest that the receptor is different from the classical mammalian AT1 and AT2 receptors. PMID- 8447505 TI - Effect of arginine analogues on hemodynamic responses in conscious rats. PMID- 8447506 TI - Cognitive style and perception: the relationship between category width and speech perception, categorization, and discrimination. AB - Category width, as defined by Pettigrew's (1958) Category Width Scale, is a cognitive variable that purportedly reveals individual differences in categorization strategy. Subjects differ in terms of broadness and narrowness of judgments of category width--to what extent they will accept exemplars as good instances of a category. We tested the hypothesis that category width would be related to how subjects behave in different speech perception tasks. Differences found between extremely broad and narrow categorizers on such tasks would be helpful in understanding the nature of the perceptual and cognitive processes underlying the category width distinction. No effects attributable to category width were found when results were analyzed in terms of subjects' (a) discrimination and feature evaluation of auditory and visual information in speech events, (b) integration of these sources of information, (c) the process of decision, and (d) subjective preference for a two-choice versus a nine-choice response method. The results from both male and female and broad and narrow categorizers supported the predictions made by a fuzzy logical model of perception (FLMP). In the FLMP, people have access to continuous information about each feature of a stimulus, they make independent evaluations of each feature based on this information, the various features are integrated, and a decision is made based on the relative support for the viable alternatives. Given the common processes involved in speech and other pattern perceptual-recognition tasks, we conclude that fundamental processes involved in pattern recognition are unlikely to vary with personality measures, such as category width. PMID- 8447507 TI - Effects of surface features on word-fragment completion in amnesic subjects. AB - Patients with amnesia resulting from alcoholic Korsakoff syndrome and elderly control patients studied a list of words in two typographies (typed and handwritten) and then received a word-fragment completion test (e.g., -ys-e-y for mystery) in which the test cues also varied in typography. Unlike the elderly control patients, the amnesic patients did not show greater priming effect when the typography at test matched that at study. The amount of typography-dependent priming was positively correlated with the score on the Wechsler Memory Scale. These results suggest that the effects of typography change on repetition priming in word-fragment completion reflect explicit recollection, and that the representation that supports repetition priming effects observed with amnesic subjects in the word-fragment completion task does not code typography information. PMID- 8447508 TI - Gastric mucosal calcinosis. Calcified aluminum phosphate deposits secondary to aluminum-containing antacids or sucralfate therapy in organ transplant patients. AB - We have noticed calcium deposits (gastric mucosal calcinosis, or GMC) in the superficial gastric mucosa of 28 organ transplant patients (OTPs) (11 liver, seven bone marrow, four kidney, three kidney/pancreas, two heart, and one each of liver and kidney transplant) who underwent endoscopic biopsies. The deposits were tinctorially similar to cytomegalovirus inclusions, ranged from 40 to 250 mu in diameter, and were present just beneath the surface epithelium at the tips of the foveolae. An x-ray microanalysis showed that these mucosal deposits contained the elements aluminum, phosphorus, calcium, and chlorine. Clinical chart review showed that all OTPs with GMC were taking aluminum-containing antacids or sucralfate. Review of biopsies from gastric ulcer patients found GMC in a significantly smaller percentage than in transplant patients (32.7% vs. 5.1%, p < 0.0002). In addition, all three ulcer patients with calcified deposits were chronic renal failure patients on long-term aluminum-containing antacid therapy. Gastric mucosal calcinosis appears to be caused by aluminum phosphate accumulation secondary to antacid or sucralfate therapy in organ transplant patients. The presence of GMC in OTPs and chronic renal failure patients rather than other gastric ulcer patients is most likely due to the longer duration of therapy with aluminum-containing compounds in the former two patient groups. The clinical relevance of GMC remains to be seen. In theory, however, accelerated bone demineralization via loss of phosphates and absorption of aluminum in the gastrointestinal tract may be a consequence of long-term aluminum-containing antacid or sucralfate therapy. PMID- 8447509 TI - Small noncleaved cell lymphoma associated with florid epithelioid granulomatous response. A clinicopathologic study of seven patients. AB - The finding of epithelioid granulomas has been widely reported in solid tumors and in hematologic malignancies. This phenomenon has been especially well studied in Hodgkin's disease, where its presence has been shown to confer a favorable prognosis. Such granulomas have not, however, been as extensively studied in other forms of hematologic malignancy, particularly in small noncleaved cell lymphoma. We report seven cases of small noncleaved cell lymphoma that were associated with a marked epithelioid granulomatous response. Detailed clinical data, including follow-up, were available in five of the seven patients. Three had localized disease (stage I), whereas two had advanced disease (stages III-A and IV-B, respectively). All five patients achieved a complete remission and are alive without evidence of disease (median follow-up, 6 years). These findings suggest that the epithelioid granulomas may be a manifestation of a host response that confers an improved prognosis in this subtype of non-Hodgkin's lymphoma. PMID- 8447510 TI - Osteoblastoma with cartilaginous matrix. An unusual morphologic presentation in 18 cases. AB - By definition, the occurrence of cartilaginous matrix in a bone-forming tumor eliminates the diagnosis of osteoblastoma and suggests a possible diagnosis of osteosarcoma. However, this rule is not absolute, as demonstrated by 18 cases of osteoblastoma that produced cartilaginous matrix. Hyaline cartilage was detected in four cases, and chondro-osteoid material was detected in 14 cases. In all patients, the tumor was in the appropriate patient age range and location for an osteoblastoma. The radiographic features as well as the histology, with the exception of the cartilaginous components, were in keeping with diagnosis of osteoblastoma. Intralesional excision (curettage or debulking) was performed in 13 patients and wide resection in five patients. Persistent tumor in one patient required a further intralesional excision. There were four recurrences, and no metastases were reported after follow-up of 1 to 23 years. The presence of cartilaginous matrix in a bone-forming lesion does not exclude the diagnosis of osteoblastoma and, more importantly, it is not always an indication that the tumor is an osteosarcoma. PMID- 8447511 TI - The clinicopathological meeting. A means of auditing diagnostic performance. AB - The clinicopathological meeting is one of the major areas of contact between clinician and pathologist, and the review of histology reports at such meetings can be regarded as an aspect of quality control for diagnostic pathology. To assess the effects of this review, we have conducted a formal analysis of clinicopathological meetings in the Southampton University Hospitals. Over a 14 week period, 416 cases were reviewed at 58 meetings. Seven categories of meeting were involved; Breast; Dermatology; Ear, Nose, and Throat (ENT) and Oral Surgery; Gastroenterology; General Surgery; Oncology; and Urology. A proforma was completed for each case that was reviewed, evaluating changes in diagnosis, the reason for such changes, and the effect, if any, on patient management. Participating consultants, both clinicians and pathologists, were questioned regarding the aims of their particular meeting, and how successful they felt the meeting to be. Histological review resulted in an altered diagnosis in 9% of cases, a refined diagnosis in 10% of cases, and no diagnostic change in 81%. Most (88.1%) of the diagnostic changes were attributable to the specialist expertise of the reviewing pathologist, and only 4.8% resulted from the clinicians providing extra information. Amended diagnoses led to major management changes in 16 cases (3.8%), minor management changes in 12 cases (2.9%), and no management change in 388 cases (93.3%). The Gastroenterology meeting showed the highest figures for clinically significant diagnostic changes; there was an amended diagnosis in 44.2% of cases reviewed, 83.3% of which altered patient management. These figures were related to the specialist review of endoscopic biopsy specimens. Although the variation in the methods used to select cases for review and the different roles of individual meetings prevent their adoption into a formal systematic audit scheme, analysis of case review at clinicopathological meetings can yield valuable information concerning departmental diagnostic performance. PMID- 8447512 TI - Collagenous colitis associated with chronic constipation. AB - We present a case in which the classical histopathologic features associated with collagenous colitis were present throughout the colectomy specimen of a 69-year old woman operated on for life-long intractable idiopathic constipation. This patient had never suffered from episodes of watery diarrhea. The reasons for this paradox are unclear, but suggest that a thickened collagen table and damaged surface epithelium may not be entirely specific pathologic findings marking the clinicopathological syndrome of collagenous colitis. PMID- 8447513 TI - Lymph node pseudotumor. PMID- 8447514 TI - T-cell lymphoblastic lymphoma with blood eosinophilia and associated myeloid malignancy. PMID- 8447515 TI - Disease threats in Somalia. AB - During this time of war and famine in Somalia, disease threats are encyclopedic both for Somalis and visitors. Malnutrition will amplify the magnitude and severity of endemic tropical infectious diseases. Necessary crowding around life saving food distribution centers could turn focal infectious disease outbreaks into large epidemics. PMID- 8447516 TI - The effects of hemoglobin genotype and ABO blood group on the formation of rosettes by Plasmodium falciparum-infected red blood cells. AB - The mechanisms by which the hemoglobin genotype AS protect against severe malaria are not fully understood. We have investigated the possibility that protection might be achieved through an inability of red blood cells (RBC) with the AS genotype to form rosettes with RBC infected by Plasmodium falciparum. No evidence was obtained to support this hypothesis because RBC with the AS genotype formed rosettes with wild isolates of P. falciparum as readily as RBC with the AA genotype. However, the previous finding that parasitized RBC form rosettes more readily with RBC belonging to group A or B than with RBC belonging to group O was confirmed even in fresh clinical isolates. PMID- 8447517 TI - Suppressed peripheral and placental blood lymphoproliferative responses in first pregnancies: relevance to malaria. AB - An understanding of processes that predispose pregnant women, and in particular primigravidae, to malaria infection is essential to improve malaria management in pregnancy. Lymphoproliferative responses to malaria-specific (F32, 190L, and 190N) as well as other antigens (Candida and purified protein derivative [PPD]) were examined in the peripheral and placental blood of 102 Gambian women at the time of delivery. The lymphoproliferative responses of placental cells were poor to all antigens compared with those of peripheral blood (Candida P < 0.001, PPD P < 0.001, F32 P = 0.008, 190L P = 0.003, and 190N P = 0.10). Reduced proliferative capacity of placental mononuclear cells may contribute to heavy parasite colonization of this organ. Proliferation to malarial and PPD but not Candida antigens was selectively suppressed in peripheral and placental blood of primiparae relative to multiparae (F32 P = 0.07, 190L P = 0.09, 190N P = 0.007, PPD P = 0.09). Autologous plasma contained factors that suppressed lymphoproliferative responses to the same series of antigens to which the primiparae responded poorly (F32 P < 0.001, 190L P < 0.001, 190N P < 0.001, PPD P = 0.03). Malarial antibody levels were comparable among women of different parities and between peripheral and placental blood. Primigravidae may be more susceptible to malaria because of unique physiologic factors, such as higher levels of circulating immunosuppressive corticosteroids (P < 0.001), rather than differences in levels of acquired immunity. PMID- 8447518 TI - Predominance of CD8+ T lymphocytes in the inflammatory lesions of mice with acute Trypanosoma cruzi infection. AB - Using glycol methacrylate in conjunction with avidin-biotin-peroxidase complex techniques, we studied the contribution of T cell subsets to tissue inflammation during acute Trypanosoma cruzi infection. Two mouse/parasite model systems whose parasitology and pathology behaved differently were used. In C57Bl/6J mice infected with the T. cruzi Brazil strain, the levels of parasitism in blood and tissue (myocardial and skeletal muscle) reached a maximum at week 6 and decreased rapidly thereafter. Inflammatory responses in tissue corresponded with the parasitism, but decreased in intensity more gradually than that of parasitism. The T lymphocytes (Thy 1.2+) were found to be the major lymphocyte population in inflammatory cardiac and skeletal muscles (64.6-81.2%) at both three and six weeks postinfection. Among T cells, CD8+ cells (47.0-58.9%) significantly outnumbered CD4+ cells (9.3-18.6%). The number of B cells (0-1.0%) and macrophages was low. Experiments using C3H/HeSnJ mice infected with the Sylvio X10/4 clone of T. cruzi at 30 days postinfection resulted in similar findings except for a higher CD8+:CD4+ ratio. The primary finding of this study is that Thy 1.2+CD8+CD4- T lymphocytes are the major cell population in both heart and skeletal muscle in acute murine T. cruzi infection. The predominance of CD8+ T cells coincident with the decrease in the tissue parasite burden suggests a role for CD8+ T cells in the control of T. cruzi at the level of the infected cell. PMID- 8447519 TI - Increased human T lymphotropic virus type-1 (HTLV-1) proviral DNA in peripheral blood mononuclear cells and bronchoalveolar lavage cells from Japanese patients with HTLV-1-associated myelopathy. AB - Human T lymphotropic virus type-1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is endemic in tropical areas and in southwestern Japan, and has now been identified among risk groups in the United States and some European countries. Patients with HAM/TSP may also have T lymphocyte alveolitis related to the HTLV-1 infection. To quantify proportions of HTLV-1-infected cells, a fragment of HTLV-1 proviral DNA was amplified from peripheral blood mononuclear cells (PBMC) and bronchoalveolar lavage (BAL) cells obtained from patients with HAM/TSP, non-HAM/TSP HTLV-1 carriers with chronic pulmonary inflammation, and asymptomatic HTLV-1 carriers. The proportion of HTLV-1-infected cells in PBMC from patients with HAM/TSP was much higher (3-30%) than that from asymptomatic HTLV-1 carriers (mostly < 1%), based on findings with the quantitative polymerase chain reaction. In non-HAM/TSP carriers with chronic pulmonary inflammation, HTLV 1-infected cells in PBMC were also increased, but not as markedly as that seen in patients with HAM/TSP. Integration of HTLV-1 was also noted in BAL cells from patients with HAM/TSP or non-HAM/TSP carriers with chronic pulmonary inflammation. However, in patients with HAM/TSP, there was a marked increase in HTLV-1-infected cells in the lung (7.5-30% of BAL cells), as compared with findings in non-HAM/TSP carriers (< 5%). These results suggest that increased HTLV-1 proviral DNA loading may play an important role in the development of T lymphocyte alveolitis and myelopathy in patients with HAM/TSP. PMID- 8447520 TI - Comparative efficacy of clearing-dose and single high-dose ivermectin and diethylcarbamazine against Wuchereria bancrofti microfilaremia. AB - To compare the efficacy and tolerability of various combinations of low- and high dose ivermectin and diethylcarbamazine (DEC), 59 persons with Wuchereria bancrofti microfilaremia were enrolled in a double-blinded six-arm clinical trial in Leogane, Haiti. On day 1, study participants were treated with low clearing doses of ivermectin, DEC, or placebo; on day 5 they received 200-400 micrograms/kg of ivermectin or 6 mg/kg of DEC. Adverse reactions, which were generally mild, occurred more frequently with ivermectin than with DEC. One year after treatment, the geometric mean microfilarial density returned to 0.9% of pretreatment levels for persons who received a total of 420 micrograms/kg of ivermectin. This rate was significantly lower than 5.6% for persons who were treated with 220 micrograms/kg of ivermectin (P = 0.02) and 9.3% for those receiving 6 or 7 mg/kg of DEC (P = 0.006). Persons treated with a clearing dose of ivermectin followed by 6 mg/kg of DEC also had low microfilarial densities (1.7% of pretreatment levels), suggesting an additive or synergistic effect of the two drugs. The addition of a clearing dose neither reduced the severity of adverse reactions nor improved the efficacy of high-dose ivermectin. Community based intervention trials are now warranted to determine the feasibility and effectiveness of mass chemotherapy with single high-dose ivermectin for the prevention and control of lymphatic filariasis. PMID- 8447521 TI - Tolerance and efficacy of single high-dose ivermectin for the treatment of loiasis. AB - A study was carried out in southeastern Gabon to evaluate the tolerance and efficacy of single high doses of ivermectin in 31 Loa loa-infected subjects with low-to-moderate parasitemia (7-7,700 microfilaria/ml). The first group of 16 subjects received 300 micrograms/kg of ivermectin and, seven days later, a second group of 15 received 400 micrograms/kg. Complete clinical and biological monitoring was carried out during the first 10 days post-treatment and again after one and three months. All subjects continued with their usual activities during the study. The clinical tolerance of treatment was very good, and except in one case, only mild adverse reactions were observed, with pruritus being the most common symptom. There were no significant changes in blood or urine function test results or in hematologic results, except for a pronounced eosinophil reaction. The 400 micrograms/kg dose of ivermectin equaled or surpassed in tolerance that of 300 micrograms/kg dose. After treatment, L. loa microfilaremia decreased rapidly to less than 9% of the pretreatment value by day 10. This decrease was enhanced with the 400 micrograms/kg dose, although differences between the two groups diminished slightly with time. At 100 days post-treatment, the microfilaremia was still at less than 10% of the initial values in the two groups, which may indicate an effect of ivermectin on the adult worms. PMID- 8447522 TI - Iron chelation as a chemotherapeutic strategy for falciparum malaria. AB - To examine the effect of iron chelation against human malaria, 37 Zambians with asymptomatic Plasmodium falciparum infections were randomly assigned to 72-hr infusions of desferrioxamine B or placebo. Mean concentrations of ring forms decreased significantly with desferrioxamine B (P < 0.001) but not with a placebo. Over seven days of observation, mean parasite concentrations remained at the initial levels in six individuals originally given placebo, but decreased promptly with administration of desferrioxamine B (P = 0.001). Mean parasitemia was significantly lower for up to four weeks in 16 subjects treated with desferrioxamine B when compared with the eight who had received placebo only (P = 0.027). We conclude that iron chelation has antiplasmodial activity and may offer a new therapeutic strategy for falciparum malaria. PMID- 8447524 TI - Measurement of the lactate dehydrogenase activity of Plasmodium falciparum as an assessment of parasitemia. AB - This report describes an enzyme assay for the detection of Plasmodium falciparum. The assay is based on the observation that the lactate dehydrogenase (LDH) enzyme of P. falciparum has the ability to rapidly use 3-acetyl pyridine NAD (APAD) as a coenzyme in the reaction leading to the formation of pyruvate from lactate. Human red blood cell LDH carries out this reaction at a very slow rate in the presence of APAD. We measured the development of APADH and found that the formation of this product could establish the basis of an assay that detected the presence of P. falciparum from in vitro cultures at parasitemia levels of 0.02%. We also had occasion to use this assay with clinical samples. We found a correlation between levels of parasitemia and the activity of parasite LDH. Parasite LDH (pLDH) activity could be measured in blood hemolysates and in plasma and serum from patients with malaria. We used the serum assay for pLDH and followed the level of pLDH in a patient with cerebral malaria prior to antimalarial treatment and during the recovery period. From these initial studies, it is evident that the measurement of pLDH has a correlation with parasitemia and may offer a method that can be developed into a simple test for the detection of Plasmodium parasitemia. PMID- 8447523 TI - A sensitive serodiagnostic test for onchocerciasis using a cocktail of recombinant antigens. AB - A specific serodiagnostic test for onchocerciasis has been a priority objective of the World Health Organization. Fragments of cDNA encoding Onchocerca volvulus antigens selected on the basis of their specificity for this parasite were subcloned into a protein purification and expression system. No individual recombinant antigen showed a high sensitivity in an enzyme-linked immunosorbent assay because of heterogeneity in the response of O. volvulus-infected individuals. However, a cocktail of three recombinant proteins showed 96% sensitivity with 100% specificity, compared with 99% sensitivity and only 59% specificity against a crude O. volvulus extract. The sensitivity of detection of individual antigens varied between sera taken from individuals from different geographic areas infected with O. volvulus, but when used as a cocktail, all but one of the microfilaria-positive individuals from all the geographic areas studied were detected. Recombinant probes provide a practical basis for specific diagnostic tests for helminth infections. PMID- 8447525 TI - Evaluation of a nonisotopic DNA assay kit for diagnosing Plasmodium falciparum malaria in Madagascar. AB - This study evaluated a nonisotopic DNA assay kit for diagnosing Plasmodium falciparum malaria in an area of Madagascar where all Plasmodium species of human malaria are present and where malaria is endemic. Blood samples from 440 healthy children and 20 healthy adults were processed and assayed in a single day in a blind protocol. The parasitemia levels of the four Plasmodium species were determined by microscopic examinations and by counts of numbers of malaria parasites per 1,000 white blood cells. Relative to P. falciparum infections, the DNA assay results agreed with those of microscopy for 207 positive and 239 negative samples; two samples were scored as positive by the DNA probe that were not detected by microscopy, and 12 samples were scored as positive by microscopy but were not detected by the assay. Relative to microscopy, the sensitivity of the assay was 95%, the specificity was 99%, and the effective sensitivity threshold of the DNA probe assay was approximately 30 parasites/mm3 of blood. The assay did not detect infections with either P. vivax, P. malariae, or P. ovale alone, but detected mixed infections of P. falciparum with either P. vivax or P. ovale. With this nonisotopic DNA probe assay, we were able to process large numbers of samples efficiently and to detect P. falciparum malaria infections with high sensitivity and specificity in a population that did not display overt disease symptoms. PMID- 8447526 TI - Mortality and sequelae due to cerebral malaria in African children in Brazzaville, Congo. AB - This study was carried out on 170 children admitted to the University Hospital of Brazzaville (Congo) for cerebral malaria between January 1, 1988 and June 30, 1989. The selection criteria were 1) unarousable coma, cerebrospinal fluid without microorganisms or a marked cellular reaction, and the absence of other causes, and 2) that the children lived in Brazzaville. The case fatality rate was 15%. In 75% of the cases, death occurred within the first 48 hr. The prognosis worsened with the stage of the coma and a younger age. At discharge from the hospital, 9% of the cases presented with sequelae. The postcerebral malaria mortality was high; indeed, death occurred in six (7%) of 90 children discharged from the hospital whose parents were contacted between nine and 27 months later. Two deaths were directly related to neurologic sequelae. Among the 58 children examined under satisfactory conditions between nine and 27 months (mean 16.9 months) after discharge, 50% (3 of 6) still presented with attenuated forms of the sequelae observed immediately after the episode of cerebral malaria (cortical blindness had regressed completely, unlike ataxia and loss of balance). Disorders that may have been related to the episode of cerebral malaria were observed in 31% of these 58 cases. PMID- 8447527 TI - High levels of interferon alpha in the sera of children with dengue virus infection. AB - We measured the levels of interferon alpha (IFN alpha) in the sera of Thai children hospitalized with dengue hemorrhagic fever (DHF) or dengue fever (DF) to examine the role of IFN alpha in dengue virus infections of humans. The percentage of patients who had detectable levels of IFN alpha (> or = 3 U/ml) was higher in patients with DHF (80%, P < 0.001) and in patients with DF (60%, P < 0.001) than in healthy Thai children (7%). The levels of IFN alpha were higher in patients with DHF and in patients with DF on the first few days after the onset of fever than in healthy Thai children. The average levels of IFN alpha in patients with DHF were high two days before defervescence, decreasing gradually until the day of defervescence. There was a subset of patients with DHF who had increasing levels of IFN alpha after defervescence. However, the levels of IFN alpha in patients with DF were not high after fever subsided. The levels of IFN alpha were not different among children with DHF grades 1, 2 and 3. Among patients with DHF, T lymphocytes were activated to a higher degree in high IFN alpha producers than in low IFN alpha producers. These results indicate that similarly high levels of IFN alpha are produced in vivo during the acute stages of DHF and DF, and that high levels of IFN alpha remain after fever subsides in some patients with DHF, but not in patients with DF. PMID- 8447528 TI - Prevalence of serum antibodies to human T lymphotropic virus-1 in an isolated tribe in the highlands of Irian Jaya, Indonesia. AB - There have been several recent reports on the high prevalence of serum antibodies to human T lymphotropic virus-1 (HTLV-1) in isolated populations residing in the coastal areas and highlands of Papua New Guinea. In the absence of significant cases of clinical disease, it has been surmised that this reactivity might be the consequence of serologic recognition of yet undefined human retroviruses or parasite antigens. These observations prompted an investigation of the prevalence of anti-HTLV-1 antibodies among members of the Ngalum tribe that dwells in a secluded highland valley in the eastern Jayawijaya Mountains of Irian Jaya, Indonesian New Guinea. Of 165 tribespeople, 85 (52%) were positive for IgG antibodies to HTLV-1 in an indirect enzyme-linked immunosorbent assay. Eighty-two were more than 10 years of age. On the Western blot, all positive sera reacted strongly with the p19 core antigen, but recognition of the envelope antigens, gp46 and gp21, was conspicuously absent. Thirty-four of the 85 villagers with these indeterminant blots had active Plasmodium falciparum infections, but antibody absorption studies with HTLV-1 and P. falciparum erythrocytic stage antigens failed to confirm suspected serologic cross-reactivities. Thirty-three others had acute malaria and/or high titers of anti-malaria antibodies but were seronegative for HTLV-1. We suspect that indeterminant Western blots for HTLV-1 reflect antibody responses to related latent retroviruses that are activated as a consequence of immunosuppression following malaria infection and chloroquine therapy. PMID- 8447529 TI - Mediterranean spotted fever in Marseille, France: correlation between prevalence of hospitalized patients, seroepidemiology, and prevalence of infected ticks in three different areas. AB - We report the results of a comparison of several epidemiologic and ecologic parameters affecting the incidence and seroprevalence of Mediterranean spotted fever (MSF) in northern, central, and southeastern Marseille, an area endemic for this disease. In northern Marseille, the incidence of hospitalized patients with MSF was 24.2/100,000 persons compared with 9.8/100,000 and 8.8/100,000 for the central and southeastern regions, respectively. The seroprevalence in sera from blood donors, determined by microimmunofluorescence and confirmed by Western blot assays, was higher in the northern region than in the other two areas (6.7% versus 3.6% and 2.4%, respectively). This higher prevalence of MSF in the northern part of the city may be related to a greater tick exposure due to a higher number of dogs (32.6/100 inhabitants versus 28.4/100 and 27.2/100 in the central and southeastern regions, respectively) and a higher rate of infection of dogs in the northern region (51.4% versus 43.5% and 39.9%, respectively). The ratio of spotted fever group rickettsia-infected ticks was similar in both the northern and southeastern areas (14.8% and 13.4% respectively), but lower in the central area of the city (8.9%), leading to a higher risk of having MSF after a tick bite in the northern and southeastern parts of Marseille. PMID- 8447530 TI - A suburban focus of endemic typhus in Los Angeles County: association with seropositive domestic cats and opossums. AB - Thirty-three cases of locally acquired murine typhus were reported in Los Angeles County residents from May 1984 through February 1988. Only eight cases were reported over the previous 20-year period. Thirty (91%) cases resided within a suburban area encompassing approximately 50 km2 in northcentral Los Angeles or had contact with an animal from this area. Serologic testing (complement fixation and indirect fluorescent antibody) of selected animals in close association with human cases revealed a high prevalence of seropositivity among domestic cats and opossums. Nine (90%) of 10 resident cats tested had demonstrable antibody titers compared with none (0%) of 20 cats from a control area (P < 0.001). Suburban typhus cases were more likely than neighborhood controls to own a cat or dog (odds ratio = 6.9, 95% confidence interval = 1.8, 25.9, P = 0.002). Sixteen (42%) of 38 opossums trapped in close proximity to the residences of cases were seropositive versus none (0%) of 36 opossums from control areas (P < 0.001) A low frequency (2.8%) of seropositivity was found in commensal rodents, and the classic vector of murine typhus, Xenopsylla cheopis, was not found. Ectoparasite indices form seropositive opossums revealed heavy infestations with the cat flea, Ctenocephalides felis (mean flea count = 104.7), a species that readily bites humans. These data provide evidence that a suburban focus of murine typhus exists in Los Angeles that differs substantially from the classic transmission cycle, and that cats, opossums and C. felis may play an important role in the occurrence of human cases. PMID- 8447532 TI - What's in a name? An acronym or a response? PMID- 8447531 TI - Should yellow fever vaccine be included in the expanded program of immunization in Africa? A cost-effectiveness analysis for Nigeria. AB - The cost-effectiveness of preventive yellow fever vaccination versus emergency mass vaccination campaigns for epidemic control remains a matter of controversy. Until recently, Nigeria and other anglophone countries in West Africa most severely afflicted by yellow fever epidemics have followed a policy of emergency control. The effects of including yellow fever 17D vaccine in the Expanded Program of Immunization (EPI) on the immune status of the Nigerian population was studied under conservative assumptions of vaccine coverage and efficacy. The model defined the age-specific prevalence of immunity resulting from vaccination of infants and from natural endemic infection beginning in 1991 and extending over a time horizon of 35 years. The data were used to predict the number of cases and deaths during hypothetical epidemics in 2006 and 2026, representing the historic periodicity of epidemics. A second model was used to demonstrate that a > or = 60% prevalence of immunity would preclude epidemic yellow fever transmission; under base case assumptions, this prevalence would be reached after 18 years of initiating routine yellow fever vaccination in the Guinea savannah zone, the region most often affected by epidemics. Using assumptions based on data from other African countries, the cost of adding yellow fever vaccine to the existing EPI was estimated as +0.65 per fully immunized child, whereas the cost of emergency vaccination in the face of an epidemic was estimated as +7.84/person. Vaccine coverage rates achievable by the EPI were modeled on recent successes with measles vaccine, and began in 1991 at 60%. The effective vaccine coverage rate in an emergency campaign was taken as 10%, based on recent experience. For an epidemic of moderate size in 2006 (morbidity similar to the documented outbreak in 1987), the cost-effectiveness of emergency mass immunization for control of hypothetical yellow fever epidemics was two-fold higher ($381/case and $1,904/death prevented) than that of the EPI ($763/case and $3,817/death prevented). However, despite its higher cost, the efficiency of the EPI was seven-fold greater in terms of cases and deaths prevented. In large epidemics, such as that occurring over successive years (1986-1991) in Nigeria, cost-effectiveness of the EPI exceeded that of emergency control. The EPI may also play an important role in the prevention of endemic yellow fever. Assuming annual rates of endemic yellow fever predicted by serologic surveys, routine vaccination would significantly reduce morbidity and mortality at cost effectiveness ratios within the range for other diseases prevented by the EPI, including polio, tetanus, and diphtheria.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8447533 TI - Surgical treatment of common carotid artery occlusion. AB - Eight patients with common carotid artery (CCA) occlusion underwent bypass with saphenous vein to either the carotid bifurcation (five), the internal carotid artery (two), or the external carotid artery (one). Indications included ipsilateral transient ischemic attack (two), recent nondisabling hemispheric stroke (two), and transient nonhemispheric cerebral symptoms (two). Two asymptomatic patients with CCA occlusion and contralateral internal carotid stenosis underwent prophylactic revascularization prior to planned aortic surgery. There were no perioperative strokes, occlusions, or deaths. Late ipsilateral stroke occurred in two patients, and one patient had a single transient ischemic attack after 2 years. The four patients with preoperative transient cerebral ischemia experienced relief of their symptoms. Duplex ultrasound is an accurate screening modality for distal patency. Collateral filling of the internal or external carotid artery can usually be demonstrated after aortic arch or retrograde brachial contrast injection. End-to-end distal anastomosis after endarterectomy eliminates the original occlusive plaque as a potential source of emboli. The subclavian artery is preferred for inflow on the left. The CCA origin is easily accessible for inflow on the right. Bypass of the occluded CCA is safe and may be effective in relieving transient cerebral ischemic symptoms, although long-term ipsilateral neurologic sequelae may still occur. PMID- 8447534 TI - Comparison of classic and quantitative prognostic factors in hormone receptor positive and hormone receptor-negative female breast cancer. AB - The prognostic variables of 281 women with breast carcinoma (followed up for more than 8 years) were studied using Cox's analysis. Clinical and histologic features, nuclear morphometric variables, and mitotic indices were analyzed separately in progesterone receptor-negative (PR-) and -positive tumors (PR+). In PR- tumors, axillary lymph node status (p = 0.0025) and tumor size (p = 0.03) were predictors of survival in the univariate analysis. Tumor size (p < 0.0001), axillary lymph node status (p = 0.0006), the volume-corrected mitotic index (M/V index) (p = 0.0023), and the mitotic activity index (MAI) (p = 0.0067) were found to be related to survival according to univariate analysis of PR+ tumors. In PR- tumors, axillary lymph node status (p = 0.002), year of treatment (p = 0.017), and circumscription of the tumor margin (p = 0.02) had independent predictive value. In PR+ tumors, tumor size (p < 0.001), the MAI (p = 0.001), and axillary lymph node status (p = 0.04) predicted survival independently in Cox's analysis. In PR- tumors, histologic type (p = 0.008) was an independent predictor of recurrence-free survival, whereas in PR+ tumors, the M/V index (p < 0.001), tumor size (p = 0.007), and the standard deviation of the nuclear perimeter (p = 0.026) were independently related to recurrence-free survival. The results indicated that mitotic indices and nuclear morphometric variables are of limited value in predicting patient survival in breast carcinomas that are hormone receptor negative. Thus, a separate analysis is advocated for hormone receptor-positive and -negative tumors when the predictive value of quantitative measurements and histologic variables is tested in patients with breast cancer. PMID- 8447535 TI - Direct revascularization for the treatment of forearm and hand ischemia. AB - During an 8-year period, 65 patients underwent operation for ischemia of the arm and hand. Fifty-four patients presented with an acutely ischemic extremity. Twenty-two had cardiac origin emboli, 9 had arterial-arterial emboli, 8 had traumatic occlusion of the brachial artery, and 15 patients developed arterial insufficiency after iatrogenic intervention. Twenty-one of 22 patients with cardiac emboli were successfully treated with embolectomy alone. The majority of patients with arterial-arterial emboli and traumatic or iatrogenic injuries required arterial reconstruction in addition to clot retrieval. After operation, 53 of 54 patients were asymptomatic. Eleven patients underwent operation for chronic ischemia. Seven patients had axillo-brachial saphenous vein grafts, two had carotid-subclavian bypass grafts, and two patients underwent aorto-innominate bypass. All grafts remained patent during follow-up that ranged from 6 months to 8 years. We conclude that operative therapy is very effective in preventing limb loss and functional impairment in patients with acute or chronic upper extremity ischemia. PMID- 8447536 TI - Recovery from postoperative hypothermia predicts survival in extensively burned patients. AB - To clarify the cause of postoperative hypothermia in extensively burned patients, factors affecting postoperative hypothermia were studied in 16 extensively burned adult patients (8 survivors and 8 nonsurvivors) with a burn index greater than 35. Body temperature was monitored continuously in either the urinary bladder or rectum. Hypothermia of less than 35 degrees C occurred in 89% (66 of 74) of the total operations performed in these 16 patients. The rate of temperature rise (RTR) was significantly lower in nonsurvivors (0.4 +/- 0.2 degrees C/h) than in survivors (1.7 +/- 0.9 degrees C/h; p < 0.001). Continuous indirect calorimetry performed in seven patients (four survivors and three nonsurvivors) demonstrated that RTR was determined primarily by heat production. The measured energy expenditure reached only 1.7 +/- 0.2 times the basal energy expenditure during rewarming in nonsurvivors, whereas it was 2.7 +/- 0.9 times the basal energy expenditure in survivors (p < 0.01). Surprisingly, in nonsurvivors, the RTR was significantly decreased even during the first 2 weeks. These findings suggest that those who cannot generate heat well in postoperative hypothermia are unable to produce the additional energy required to overcome sepsis. PMID- 8447537 TI - Appraisal of hepaticocutaneous jejunostomy in the management of hepatolithiasis. AB - Hepaticocutaneous jejunostomy offers the advantage of permanent percutaneous access to the biliary tract in patients with complex biliary problems. The long term value, however, has not been assessed. In 41 patients who underwent this procedure for intrahepatic stones, there was no hospital mortality, and the postoperative morbidity rate was 10%. The presence of the cutaneous stoma facilitated postoperative flexible choledochoscopy for dilatation of biliary strictures and extraction of residual stones. On follow-up, symptoms recurred in 12 patients (29%) at a median time of 27 months (range: 1 to 97 months). Reconstruction of the cutaneous stoma and flexible choledochoscopy via the jejunal loop helped to resolve the acute cholangitis (n = 4) and to eradicate recurrent stones in all cases. Hepaticocutaneous jejunostomy was also beneficial in the management of three patients who experienced further recurrence of symptoms. There was no major difficulty in reconstructing the cutaneous stoma and in performing choledochoscopy via the jejunal loop. The overall complication rate related to the cutaneous stoma was 15%. Repeat laparotomy for recurrent disease was required in only one patient who underwent a second bilio-enteric anastomosis for a nondilatable left duct stricture. We conclude that hepaticocutaneous jejunostomy is a valuable procedure in the management of hepatolithiasis. PMID- 8447539 TI - Groin lymphorrhea complicating revascularization involving the femoral vessels. AB - Seven (4%) of 193 patients developed lymphoceles in 8 (2%) of 316 groin wounds after 211 arterial reconstructive procedures. Included were 91 aortic, 15 extra anatomic, and 105 infrainguinal revascularizations. Lymphoceles developed in otherwise uncomplicated wounds in 6 (8%) of 73 patients with oblique incisions and bilaterally in 1 (1%) of 120 patients with vertical incisions (p = 0.01). This difference may be related to the surgical technique, with increased lymphatic damage and inadequate wound closure in the oblique approach. No increased incidence of lymphorrhea was noted in those patients undergoing aortic reconstruction regardless of the type of incision used (p = 0.15), or when compared with patients who had undergone extra-anatomic or infrainguinal bypass (p = 0.14). Each lymphocele was persistent, and external fistulas spontaneously occurred in three. Diagnosis was based upon clinical awareness and the appearance of the groin mass. Conservative management was uniformly unsuccessful, and operative ablation of the lymph fistula and lymphocele proved to be definitive therapy. PMID- 8447538 TI - Indications and technique for the use of the porto-renal shunt in the treatment of variceal hemorrhage. AB - Although hepatic replacement has emerged as the most definitive treatment for patients with chronic liver disease with variceal hemorrhage, a significant number of patients remain better served by porto-systemic shunting. Historically, for those patients with coexisting ascites requiring side-to-side shunting, synthetic or autogenous graft material has been interposed between the portal vein and inferior vena cava when the two veins could not be brought into direct apposition. The porto-renal shunt, described in 1964 but rarely used, allows shunt construction without the use of synthetic materials. Six patients who recently underwent porto-renal shunting are described in order to clarify the indications for the use of this technique and to describe the technical aspects of its construction. PMID- 8447540 TI - Development of independent vessel security after ligation with absorbable sutures or clips. AB - The external jugular vein and the contralateral carotid artery in each of 59 rabbits were ligated with either sutures or absorbable clips and then divided. After 0, 1, 2, 4, 7, or 14 days following ligation, the suture or clip was removed, and the vessel's resistance to leakage was quantitated. When the absorbable clips were removed from arteries after 1 day, their mean resistance pressure prior to leakage was 171 +/- 46 mm Hg; in contrast, arteries ligated with a suture did not achieve independent security until after 4 days. At 4 days, the mean pressure prior to leakage of arteries with the suture removed was only 88 +/- 49 mm Hg. Similar results were obtained with veins. The difference in vessel security was attributed to the significant increase in the width of the vessel wall compressed when an absorbable clip was utilized compared with a strand of suture. PMID- 8447541 TI - A review of gene transfer techniques. AB - The ability to transfer genetic material from one cell to another provides a novel approach for the investigation and potential treatment of a variety of diseases. Several gene transfer techniques have been developed. Of these, the use of retroviruses as vectors has allowed highly efficient and stable introduction of foreign genes into target mammalian cells, thus making gene therapy possible. The current prospects are that some unusual lethal diseases can be corrected and that various forms of cancer will be treated in this manner. PMID- 8447542 TI - H. Milton: visionary surgeon. AB - Current wisdom holds that median sternotomy is the creation of cardiac surgeons as the premier approach to the heart. In fact, this innovative and resourceful procedure was perfected by an obscure English surgeon in Cairo, Egypt (U.A.R.), in 1897. H. Milton designed a vertical sternal-splitting approach for the excision of tuberculous mediastinal nodes and employed it successfully in a patient. Modern medicine owes a great debt to H. Milton for this significant, albeit unrecognized, contribution. The details of the life of this unsung surgeon, such as are known, are presented. PMID- 8447543 TI - Teaching and testing technical skills. AB - Teaching technical skills is one of the most important tasks of a surgeon. This article discusses current issues in teaching and testing technical skills. For the most part, the level of technical skills cannot be predicted before a surgical resident starts a program. Different methods of teaching technical skills are reviewed (in and out of the operating room). For optimal effectiveness in teaching residents, we must apply principles of adult learning to the surgical domain. A methodologic framework for skill acquisition, adapted from the educational psychology literature, is discussed. Five methods of assessing technical skills are presented. Structuring the assessment process has resulted in higher levels of reliability and improved validity. PMID- 8447544 TI - Endoscopic drainage of esophageal suture line leaks. AB - Suture line leaks after esophageal or gastric surgery are associated with high morbidity and mortality rates. We report a new approach to the management of this problem, which has been used successfully in the treatment of nine patients with such leaks who were treated at or referred to our unit. The suture line defect is first visualized by endoscopy, after which a sump nasogastric tube is advanced down the esophagus and out through the defect into the abscess cavity. The tubes are irrigated intermittently to achieve patency and maintained with continuous suction. Separate pleural or subphrenic collections are drained by conventional techniques. After the injection of contrast down the tube, serial radiologic studies are used to monitor progress and to guide the slow withdrawal of the tube as the cavity collapses. PMID- 8447545 TI - Alternate hemihepatic vascular control technique for hepatic resection. AB - This report describes a simple and improved inflow control technique for resection of a hepatic tumor that lies across the right and left hepatic lobes. With alternate hemihepatic inflow control by en masse occlusion of Glisson's sheath of each hemipedicle at the bifurcation, hepatic resection across the two hepatic lobes is completed. Compared with Pringle's maneuver, this technique eliminates splanchnic congestion and reduces warm ischemia of the remnant liver, while maintaining a comparable hemostatic effect. PMID- 8447546 TI - Two-clamp method to avoid portal anastomotic stenosis in liver transplantation. AB - We developed a two-clamp technique to avoid stenoses in portal anastomoses during liver transplantation. A portal anastomosis is created with a continuous polypropylene suture. A second vascular clamp is placed on the donor portal vein before release of the recipient vein clamp. After release of the proximal clamp, the vein is allowed to distend to its maximal diameter, and the suture is gently tied. This technique was used in both portal and arterial anastomoses in 43 consecutive liver transplant recipients. No cases of postoperative stenosis or thrombosis were observed. PMID- 8447547 TI - Critical scrutiny of the open "tension-free" hernioplasty. AB - Tension-free hernioplasty is rapidly gaining worldwide acceptance. Since June 1984, 3,125 consecutive adult male primary inguinal hernias have been repaired by employment of an open tension-free prosthetic repair without approximation of the margins of the defect. Since the original publication of our technique in the 1989 February issue of The American Journal of Surgery, we have encountered four recurrences. These recurrences were caused by technical errors early in our experience and have since been corrected. The purpose of this paper is to bring those errors to the attention of surgeons, as well as to suggest certain modifications to further simplify the operation. Three of the recurrences occurred at the pubic tubercle and were caused by placing the mesh in juxtaposition to the tubercle. This error has since been corrected by overlapping the mesh at the pubic bone. One recurrence was caused by disruption of the lower edge of the mesh from the shelving margin of Poupart's ligament. The error here was utilization of a patch that was too narrow and therefore under tension. It became apparent that a wider patch, fixed in place with an appropriate degree of laxity, was required. PMID- 8447548 TI - Introduction: advances in pediatric bone marrow transplantation. PMID- 8447549 TI - A continuing challenge: treatment of hemophilic children with acquired factor VIII inhibitors. PMID- 8447550 TI - Lingual hemorrhage in a patient with hemophilia A complicated by a high titer inhibitor. Management by continuous infusion of monoclonal antibody-purified factor VIII. AB - PURPOSE: The management of oral bleeding in hemophilia A patients with high titer inhibitors can be challenging. Simultaneous administration of activated prothrombin complex concentrates and antifibrinolytic agents is potentially dangerous because both agents have thrombogenic properties. We report sustained control of life-threatening lingual hemorrhage in a hemophilic patient with a high titer inhibitor (100 Bethesda Units/ml) on continuous infusion of a monoclonal antibody-purified factor VIII concentrate (75 U/kg/h). METHODS AND RESULTS: In vivo hemostasis was achieved without an initial increment in free plasma factor VIII:C. The biphasic nature of recovered factor VIII:C indicated initial antigen-antibody formation, a saturation point, then a rapid rise of free factor VIII in plasma. In vitro, rapid loss of factor VIII activity was noted in mixtures of patient's plasma and purified factor VIII during incubation at 37 degrees C. When an excess of purified factor VIII was added to patient's plasma, a plateau of stable residual factor VIII activity followed the initial loss of factor VIII activity, suggesting a second-order reaction. CONCLUSION: This type I kinetic response is typical of alloantibodies induced by exposure to factor VIII concentrates. PMID- 8447551 TI - Philadelphia chromosome-positive chronic myeloid leukemia and thoracic ganglioneuroma. Previously undescribed association. AB - A previously healthy 11 year-old-white boy presented with persistent mild leukocytosis and a posterior mediastinal mass. Surgical excision of the mass showed it to be a ganglioneuroma. Postoperatively, the patient had marked leukocytosis (white blood cell count 57,000/mm3) and a low leukocyte alkaline phosphatase score. Bone marrow aspirate for cytogenetics performed in the evaluation of the posterior mediastinal mass showed the presence of the Philadelphia chromosome (Ph) in 19 of 20 metaphase spreads. The diagnosis of Ph+ chronic myeloid leukemia (CML) was confirmed on repeat cytogenetics. Subsequent detailed skin examination showed six small cafe-au-lait spots but no other evidence of neurofibromatosis. This is the first report to describe an association between ganglioneuroma and Ph+ CML. PMID- 8447552 TI - Relief of sickle cell priapism by hydralazine. Report of a case. AB - We report a 16-year-old Tanner IV male with homozygous hemoglobin S who presented with recurrent episodes of priapism unresponsive to standard therapy with hydration, analgesia, and exchange transfusion. He had a complete resolution of his symptoms with hydralazine therapy. We therefore suggest a trial of vasodilator therapy for recurrent sickle cell priapism before attempting surgical therapy. PMID- 8447553 TI - Neonatal immune neutropenia following the administration of intravenous immune globulin. AB - BACKGROUND: In adults--but not neonates--neutropenia has been reported to complicate treatment with intravenous immunoglobulin, but the mechanism is unknown. PURPOSE: To describe for the first time the case of a newborn infant who, after intravenous immunoglobulin, demonstrated serum antineutrophil antibodies and neutropenia. PATIENTS AND METHODS: The 1,425-g, 36-week-gestation boy was healthy except for intrauterine growth retardation. Intravenous immunoglobulin (1g/dose x 3) was administered to treat alloimmune thrombocytopenia. Neutrophil-specific antibodies were detected by a granulocyte immunofluorescence assay. RESULTS: After the intravenous immunoglobulin, the platelet count normalized but the neutrophil count declined to 450/mm3. Neutrophil-specific antibodies were detected in the serum of the infant but not in the maternal serum. Furthermore, cross-matching revealed that the maternal serum did not react with the infant's granulocytes. Two of three random lots of intravenous immunoglobulin contained detectible anti-neutrophil antibodies. CONCLUSIONS: After intravenous immunoglobulin, the infant's serum contained one or more anti-neutrophil antibodies that were not maternal in origin. We speculate that the neutropenia resulted from the administration of intravenous immunoglobulin containing antineutrophil antibodies. PMID- 8447554 TI - Factitious coagulopathy due to Munchausen syndrome by proxy. PMID- 8447555 TI - Rodenticide-induced coagulopathy in a young child. A case of Munchausen syndrome by proxy. AB - PURPOSE: To present the diagnosis and management of superwarfarin ingestion, a cause of serious and prolonged coagulopathy. METHODS: Specific identification of the anticoagulant was made by high-pressure liquid chromatography. RESULTS: A 24 month-old child developed bruises and a prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT) after receiving multiple doses of brodifacoum, a superwarfarin rodenticide. The coagulopathy was treated successfully with large doses of parenteral and oral vitamin K1; fresh frozen plasma was administered as a precautionary measure on two occasions. After the first 10 days of the child's hospitalization, the mother was identified as the source of brodifacoum, exemplifying the behavior described as Munchausen syndrome by proxy. Oral vitamin K1 was initiated and continued in an outpatient setting with tapering doses over nine months, using the PT as a guide for therapy. CONCLUSIONS: This report emphasizes the necessity of recognizing rodenticide poisoning and investigating its source. Frequent monitoring of the PT is essential to prevent hemorrhagic complications due to repeat exposure, inadequate vitamin K1 therapy, or noncompliance. PMID- 8447556 TI - Spinal epidural hematoma in a hemophilic infant. AB - PURPOSE: Although intracranial hemorrhage remains a leading cause of death in hemophilia, spinal epidural hematoma is seen rarely. Decompressive laminectomy has a high associated morbidity, and recent reports have suggested that patients can be treated conservatively without surgical intervention. PATIENTS AND METHODS: We present a case of spontaneous spinal epidural hematoma diagnosed by MRI scan in a 6-month-old hemophilic infant. Immediate treatment with factor VIII replacement was instituted. RESULTS: There was rapid and complete clinical and radiographic resolution. CONCLUSION: This case shows that selected hemophilic patients with spinal epidural hematoma can be spared surgical decompression by prompt medical attention. PMID- 8447557 TI - Fetal alcohol syndrome and malignant disease: a case report. PMID- 8447558 TI - Expression of mutant p53 protein in metastasizing medulloblastoma and PNET: a prognostic marker? PMID- 8447559 TI - Biology of graft-vs.-host disease. AB - Graft-vs.-host disease (GVHD) is a major complication of allogeneic bone marrow transplantation, which is an important approach for the treatment of various diseases. In experimental animal models, lethal GVHD can be induced in major histocompatibility complex (MHC)-matched strain combinations that differ in their expression of multiple minor histocompatibility antigens. It has been shown that T cell subset populations expressing the CD8+ phenotype play an important role in the development of GVHD directed to the minor histocompatibility antigens. Moreover, highly purified preparations of these cells are capable of mediating GVHD without apparent help from mature donor-derived CD4+ T cells. CD4+ T cells can also mediate GVHD, but only in certain strain combinations. The pathogenesis of GVHD is similar, whether it is mediated by CD4+ or CD8+ T cells, with the exception that CD4+ cells may be responsible for more gastrointestinal injury. The ability of T cells to respond to minor histocompatibility antigens is further complicated by the phenomenon of immunodominance, which causes T cells to focus on a limited number of antigens out of the larger available pool. Immunodominance does occur in GVHD, but it seems to involve a different pattern of responses than those observed for the generation of cytotoxic T lymphocytes in vitro. Understanding these immunologic interactions is an important step toward the ultimate goal of developing a new approach for bone marrow transplantation, one that will avoid GVHD while retaining enough immunity to counter leukemic relapse and opportunistic infections. PMID- 8447560 TI - Mechanisms in immune recovery after bone marrow transplantation. Management of posttransplant immune deficiency. AB - PURPOSE: Bone marrow transplantation usually entails the ablation of the recipient's immune system. The recovery of immunity post-marrow transplantation is a complex process dependent on a number of pre- and posttransplant factors. This knowledge has led to the development of novel approaches to supportive care of the patient, as well as to methods of augmenting immunity. DESIGN: Hematopoietic growth factors are now used to speed neutrophil recovery. Certain lymphokines are being investigated for the enhancement of cell-mediated immunity, and gamma globulin preparations are used to support the deficiency in humoral immunity. CONCLUSIONS: This review summarizes the basic concepts of immune reconstitution posttransplant and discusses some of the therapeutic interventions that have been investigated. In addition, some general recommendations are offered regarding supportive care. PMID- 8447562 TI - Experience with recombinant factor VIIA in an infant hemophiliac with inhibitors to FVIII:C undergoing emergency central line placement. A case report. AB - An infant boy with severe factor VIII (FVIII) deficiency hemophilia and antibodies against coagulation FVIII is presented. This case is unique from the point of view of the young age of development and recognition of inhibitors to the FVIII and because this patient received recombinant factor VIIa (rFVIIa), prior to a life-saving surgical procedure. Conventional treatment options had been exhausted. The inhibitor was an IgG antibody that had rapidly increased to 100 Bethesda Units (BU). A broviac central line was placed to provide i.v. access for the purpose of treatment. Porcine FVIII had been used but an inhibitor rapidly developed to that product. Using rFVIIa, hemostasis was secured for placement of a second central line and to stop life-threatening mucosal bleeding. rVIIa was an effective treatment alternative for the management of this patient with inhibitors. PMID- 8447561 TI - Recombinant human GM-CSF treatment of neutropenia in glycogen storage disease-1b. AB - PURPOSE: Recombinant human granulocyte-macrophage colony stimulating factor (GM CSF) was administered to two patients with glycogen storage disease, type 1b (GSD 1b), with chronic neutropenia, neutrophil dysfunction, and recurrent infections in an effort to increase neutrophil counts and increase resistance to infections. PATIENTS AND METHODS: The patients' baseline absolute neutrophil counts (ANC) ranged from 56 to 480 cells/mm3 despite increased granulocyte precursors in the bone marrow. GM-CSF was given s.c. at starting doses of 500 micrograms/m2/day divided into two doses. RESULTS: After 48 h, ANC rose to 2,025 cells/mm3 and 3,132 cells/mm3, respectively. Absolute eosinophil counts also rose to 1,048 cells/mm3 (24%) and 4,820 cells/mm3 (33%) on days 10 and 9 in the two patients. Although an initial 10-day course of GM-CSF was tolerated in one patient without significant reactions, subsequent s.c. injections of GM-CSF were complicated by increasingly painful local reactions that necessitated discontinuation after 7 to 8 days. Intravenous infusion was associated with a febrile systemic reaction. Despite lack of improvement in neutrophil superoxide anion generation measured in one, both patients demonstrated unusually rapid healing of cutaneous infections on GM-CSF. CONCLUSION: Our experience suggests that GM-CSF may be useful for short-term treatment of serious infections in GSD-1b. However, alternate dosage schedules or different preparations of GM-CSF to diminish local reactions would be required for long-term maintenance therapy. Granulocyte colony stimulating factor (G-CSF) has also been shown to increase neutrophils in this disease and has not been associated with allergic reactions. PMID- 8447563 TI - Cellular pharmacology of 6-mercaptopurine in acute lymphoblastic leukemia. AB - PURPOSE: The cellular pharmacology of 6-Mercaptopurine (6MP) in acute lymphoblastic leukemia (ALL) is reviewed. DESIGN: Relevant studies on the clinical pharmacology of 6MP were reviewed. RESULTS: 6MP is one of the major drugs used in maintenance therapy of acute lymphoblastic leukemia (ALL). It is also used to treat steroid unresponsive inflammatory bowel disease. 6MP is an inactive prodrug that requires absorption, cellular uptake, and intracellular anabolism to nucleotides for cytotoxic activity. These nucleotides are ultimately incorporated into DNA and RNA, resulting in cell death. Two analogs of 6MP, azathioprine and 6-thioguanine, are also anabolized to the same intracellular metabolites, suggesting they should be therapeutically equivalent to 6MP. 6MP may be anabolized to nonmethylated nucleotides or may undergo methylation by the enzyme thiopurine methyltransferase to S-methylated nucleotides, which are also cytotoxic. CONCLUSION: Recent studies of 6MP pharmacokinetics in children with ALL have suggested that a higher systemic exposure, as measured by a greater area under the plasma concentration time curve or a higher concentration of 6MP metabolites in red blood cells, is associated with a decreased risk of relapse. PMID- 8447564 TI - Hypercytokinemia in hemophagocytic syndrome. AB - PURPOSE: The study was performed to clarify in the hemophagocytic syndrome (HPS) how cytokinemia plays a role in its pathogenesis and if cytokinemia is of prognostic value. PATIENTS AND METHODS: Serum concentrations of ferritin, interferon (IFN)-gamma, soluble interleukin-2 (IL-2) receptor, IL-6, and other cytokines were determined during the acute phase of the HPS in 29 children and three adults. Data comparing malignancy-associated (MAHS; n = 17) and infection associated hemophagocytic syndrome (IAHS; n = 15) and those comparing surviving and fatal cases were assessed. RESULTS: Hyperferritinemia and hypercytokinemia were present in all patients with HPS. Eleven of the 17 MAHS and three of the 15 IAHS cases were fatal (p < 0.05). No significant difference in cytokine concentrations was observed between MAHS and IAHS. CONCLUSIONS: In terms of cytokine effect on patient outcome, serum concentrations of IL-6 > 300 ng/L and IFN-gamma concentrations > 30 U/ml or soluble IL-2 receptor (sIL-2R) concentrations > 10,000 U/ml were considered to reflect a poor prognosis in HPS patients. PMID- 8447565 TI - High frequency of etoposide (VP-16)-related secondary leukemia in children with non-Hodgkin's lymphoma. AB - PATIENTS AND METHODS: We report patients who were treated for non-Hodgkin's lymphoma (NHL) or Ki-1 antigen-positive (Ki-1) lymphoma with a T-8801 protocol that included etoposide (VP-16) and behenoylcytosine arabinoside. RESULTS: Secondary acute myeloid leukemia (AML) developed in 5 of 38 NHL and Ki-1 lymphoma patients, and the cumulative risk at 4 years was 18.4%. The median time from the initiation of the chemotherapy to the development of AML was 21 months (range, 13 30). Four patients had a FAB M5 morphology, and one had FAB M2. In four of five examined cases, chromosomal alterations involving the long arm of chromosome 11 were demonstrated at the time of development of AML. None of the 46 NHL patients who we treated with another protocol (B-8801), using significantly higher cumulative doses of VP-16 than in the case of the patients with T-8801 and a different schedule of VP-16 administration, developed secondary AML. CONCLUSIONS: The risk of secondary AML possibly related to the use of VP-16 given twice weekly. PMID- 8447566 TI - [O2 supply, O2 consumption and the pH value of the gastric mucosa. Indicators of tissue oxygenation]. AB - The lack of a rise in global O2 consumption (VO2) after increased O2 supply (DO2) (negative O2-flux test) is an indication of adequate tissue oxygenation. We were interested in whether a negative O2-flux test precludes an improvement in regional tissue oxygenation. The pH of the gastric mucosa (pHi) is considered a sensitive marker for tissue hypoxia. Method. The study was approved by the ethics committee of our hospital. In 12 intensive-care patients with septic shock, gastric pHi was determined (Trip'TGS catheter, Tonometrics) in addition to measuring O2-transport-related parameters via invasive haemodynamic monitoring. Following the initial measurement, a further increase in the O2 supply via volume substitution was attempted in all already hyperdynamic patients with DO2 in the upper-normal range. Results. Volume substitution with 1.246 +/- 594 ml colloid resulted in an increase in pulmonary capillary wedge pressure from 14 +/- 2 mm Hg to 17 +/- 1 mm Hg (P < 0.01). All patients had an increase in DO2 from 755 +/- 192 ml/min.m2 to 846 +/- 236 ml/min.m2 (P < 0.05). There was no significant change in VO2, at 153 +/- 28 ml/min.m2 before and 156 +/- 35 ml/min.m2 after volume administration. However, pHi increased from 7.19 +/- 0.08 to 7.24 +/- 0.08 (P < 0.01). DISCUSSION AND CONCLUSION. The low pHi at the time of the initial measurement shows that regional tissue hypoxia may be present even in patients with an above-normal O2 supply > 600 ml/min.m2. Apparently, the lack of rise in global O2 consumption after increased O2 supply does not exclude a regional improvement in tissue oxygenation. The less invasive pHi measurement is an additional useful monitoring procedure for the optimisation of regional tissue oxygenation in critically ill patients. PMID- 8447567 TI - [Oral premedication with clorazepate dipotassium. Comparison with oral premedication with flunitrazepam and intramuscular premedication with promethazine, pethidine and atropine in adults]. AB - The purpose of premedication and the best form have been frequent subjects of controversy among anaesthetists in the past few years. Anxiolysis is now accepted as the main purpose. The preferred route of administration is by mouth. The intention of this study was to examine whether clorazepate dipotassium has the same sedative-hypnotic and anxiolytic effects as i.m. premedication with promethazine, pethidine and atropine. METHODS: A total of 100 patients aged 20-65 years and due to undergo arthroscopy took part in this study. Patients in group I were given 1 mg flunitrazepam p.o. on the evening before the operation and the i.m. premedication described above. The premedication for group II consisted in clorazepate dipotassium, 50 mg on the evening before operation and 25 mg on the morning of the day of the operation. The sedative-hypnotic effects were measured on a four-point scale. The Erlangen anxiety scale (EAS) and a visual analogue scale (VAS) were used to evaluate the anxiolytic effects according to the patient's own and the observer's evaluation of mood. In addition to this, we measured amnesia, heart rate and blood pressure. RESULTS: Clorazepate dipotassium or flunitrazepam p.o. significantly reduces anxiety 1 h after administration as measured by the EAS (P < 0.05) on the evening before the operation. This result was not, however, confirmed by the VAS for self-assessment. Patients who received premedication with clorazepate dipotassium are less anxious on the morning of the operation than patients given flunitrazepam the evening before the operation (P < 0.05); this, however, does not correspond to the VAS results. There were no differences in the other parameters compared. DISCUSSION: Oral premedication with clorazepate dipotassium has the same sedative-hypnotic, anxiolytic and amnestic effects as i.m. premedication with promethazine, pethidine and atropine. The results of this study are better than those obtained by Tolksdorf et al., owing to the higher dosage used in our study (50 mg as against 20 mg). Tolksdorf et al. [21] failed to show any improvement on a placebo. Our results correspond to those of Drautz et al. [2] who used 50 mg of clorazepate dipotassium on the evening before and 25 mg on the morning of the day of the operation. PMID- 8447568 TI - [Does the photoplethysmographic technique show an improvement in the measurement of the indirect blood pressure in intensive care patients?]. AB - In the present report we investigated whether oscillometric and plethysmographic arterial blood pressure measurement techniques yielded different results compared to invasive blood pressure measurements in 18 mechanically ventilated and 14 spontaneously breathing patients. METHODS. Blood pressure was recorded simultaneously with plethysmographic, oscillometric, and invasive systems (FINAPRES 2300, HP 78352A, and 78534A, respectively). Invasive measurements were obtained in the radial artery. Short tubing was chosen in order to avoid transmission errors. The finger cuff of the FINAPRES 2300 was placed on the ipsilateral middle phalanx of the middle finger. The cuff of the oscillometric system was located on the contralateral arm. Differences in arterial blood pressure had been excluded. RESULTS. Histograms of the differences in the various pressure measurements, linear regression, and correlation coefficients were determined for quantitative comparison. The two non-invasive measurement devices (FINAPRES 2300, HP 78352A) yielded similar results in spontaneously breathing patients. In ventilated patients the reliability of oscillometric measurements was worse than that of the photoplethysmographic, especially for diastolic and mean arterial blood pressure values (Table 1, Figs. 2-4). DISCUSSION. The reasons for the differences between invasive and non-invasive measurement techniques are most likely due to problems with cuff handling for the plethysmographic device and the principles of oscillometric measurement. Both methods have to be optimised in hardware and software. However, the photoplethysmographic results showed an improvement in blood pressure measurement in ventilated patients. Due to the remaining deviations between the non-invasive and invasive measurements, especially in critically ill patients in the intensive care unit, direct measurement cannot be replaced by either of the non-invasive methods. PMID- 8447569 TI - [Hepatic venous and mixed venous O2 saturation during catecholamine therapy in patients with septic shock]. AB - Mixed venous O2-saturation (SvO2) reflects the ratio of global O2 supply to O2 consumption. However, in septic shock, there may be alterations in the ratio of regional O2 supply to O2 consumption, particularly in the splanchnic region. The aim of the study was therefore to investigate the relation between SvO2 and hepaticovenous O2-saturation (ShvO2) in septic shock with different catecholamine regimens. METHOD. Following approval of the ethics commission at our hospital, SvO2 and ShvO2 were measured simultaneously in 29 patients (7.5-F pulmonary arterial catheter). RESULTS. SvO2 and ShvO2 showed a considerable inter individual difference with values between 1.3 and 36.9% and a mean of 14.7 +/- 9.3%. Alterations of ShvO2 were only tendentially reflected in alterations of the SvO2. Under different catecholamines SvO2 and ShvO2 showed the same changes but varying in extent (Table 1; Fig. 2). After switching the catecholamine therapy from dobutamine to epinephrine, SvO2 decreased only from 76.7 +/- 3.6 to 76.1 +/- 2.3 but ShvO2 from 61.4 +/- 8.1 to 54.2 +/- 10.3%. When the therapy was switched from dobutamine to norepinephrine, SvO2 decreased from 74.8 +/- 4.9% to 68.5 +/- 4.8%, ShvO2 decreased from 61.9 +/- 12.9% to 49.2 +/- 12.8%. When dopamine was added to norepinephrine, SvO2 increased from 68.6 +/- 4.3% to 73.6 +/- 4.4%, ShvO2 increased from 52.6 +/- 12.7% to 63.7 +/- 9.8%. When dopexamine was added to dobutamine, SvO2 increased from 74.6 +/- 4.5% to 76.9 +/- 2.5%, while ShvO2 increased from 57.6 +/- 11.5% to 58.8 +/- 13.4%. DISCUSSION AND CONCLUSION. The results presented show that SvO2 does not provide sufficient information about the venous O2 saturation of the splanchnic region. The intraindividually variable differences between SvO2 and ShvO2 during therapeutic interventions demonstrate that a selective alteration of blood supply to or O2 consumption of the splanchnic region has taken place, which is insufficiently reflected by the SvO2. PMID- 8447570 TI - [Methods of interpreting pulmonary gas exchange]. AB - When arterial and mixed venous blood gas tensions, inspired and expired O2 and expired CO2 concentrations are known, it is possible to calculate the alveolar arterial PO2 difference, intrapulmonary right-to-left shunt and dead space ventilation. However, because arterial hypoxemia is caused by ventilation/perfusion mismatching in most cases, a method allowing analysis of ventilation/perfusion ratios is needed. The "multiple inert gas elimination technique" (MIGET) is a powerful method that is useful for this purpose. This technique is based on measurements of arterial, venous and expired levels of inert gases spanning a wide range of solubility and analysis of the lung for the ventilation/perfusion ratios from true shunt to dead space ventilation. True shunt, with ventilation/perfusion ratios of 0, can be differentiated from ventilation/perfusion ratios of 0.005, and dead space ventilation can be distinguished from ventilation/perfusion ratios over 10 and under 100. Ventilation/perfusion ratios between these extremes can also be differentiated. It is not unusual for results yielded by MIGET to differ from those obtained with O2-dependent methods: O2 shunt generally exceeds MIGET shunt, for example, because O2 shunt includes low ventilation/perfusion units. PMID- 8447571 TI - [The reliability of the measurement of non-invasive oscillometric blood pressure instruments]. AB - METHODS: The performance of five oscillometric blood pressure monitors was tested by means of a simulator. The oscillometric signals of two healthy patients were replayed. These signals were superimposed by sinusoidal artefacts with increasing amplitude, to examine the influence of artefacts on the accuracy of the measurement. Each measurement was repeated 15 times. RESULTS: The artefacts taken for this examination did affect the scattering of each single measurement rather than the mean value of the repeated measurements. The results did get worse with decreasing signal-to-artefact ratio. However, some monitors are able to handle these artefacts better than others. CONCLUSION: It is obvious that the implemented software for the artefact treatment and the determination of blood pressure values differs from manufacturer to manufacturer. Some devices were able to separate relevant signals from artefacts better than others. The most critical point of the oscillometric method is the correct determination of the maximum amplitude of the oscillations, because it directly influences the accuracy of the displayed blood pressure values. The availability of a simulator to test automated sphygmomanometers has shown to be a good tool to examine the performance of these devices. PMID- 8447572 TI - [Anesthetic-induced heart arrest. A case report of 2 infants with previously unrecognized muscular dystrophy]. AB - We report two boys aged 4 and 10 months who suffered cardiac arrests after induction of anaesthesia. Both infants had no personal or family history of myopathy. In both cases anaesthesia was induced by inhalation with halothane and N2O/O2 (70/30). To facilitate tracheal intubation both were given succinylcholine after the administration of atropine. The 4-month-old developed muscle rigidity and cardiac arrest occurred immediately after tracheal intubation. Resuscitation was unsuccessful. Laboratory findings during resuscitation showed elevated serum potassium levels of more than 10 mmol/l and serum creatine phosphokinase 17.700 IU/l. Histopathologic examination of the skeletal muscle revealed congenital muscular dystrophy. In the older boy no muscle contractures were noted after administration of succinylcholine. He developed bradycardia that progressed to asystole 15 min after induction of anaesthesia. After 1 h of resuscitation a sinus rhythm could be established. The boy developed myoglobinuria and his serum creatine phosphokinase reached a maximum level of 45,000 IU/l on the 2nd day. The child survived and made a complete recovery. Two months later a muscle biopsy taken from the quadriceps showed marked muscular dystrophy. Duchenne's muscular dystrophy could be excluded. The most likely underlying reasons for these complications are discussed: anaesthesia-induced acute rhabdomyolysis or malignant hyperthermia. PMID- 8447573 TI - [Comments on the work by R. Beyer and W.C. Seyde. Propofol versus midazolam. Long term sedation in the intensive care unit]. PMID- 8447574 TI - [Comments on the work by E. Waldhausen and G. Keser. Paralysis caused by carbohydrates during intensive therapy]. PMID- 8447575 TI - [The first treatise on ether anesthesia in Germany dated 1847]. PMID- 8447576 TI - Halothane: ave atque vale. PMID- 8447577 TI - Traumatic tracheal transection. PMID- 8447578 TI - Bilateral lingual nerve injury following tracheal intubation. PMID- 8447579 TI - Bilateral pneumothorax and surgical emphysema associated with laparoscopic cholecystectomy. PMID- 8447580 TI - Noninvasive assisted ventilation in hypercapnic respiratory failure. PMID- 8447581 TI - Efficacy of ketamine infusion in refractory asthma complicated by acute myocardial infarction. PMID- 8447582 TI - Spontaneous Clostridium perfringens lung abscess unresponsive to penicillin. AB - Clostridial necrotising pneumonia is a rare complication of aspiration, bronchial tumour or foreign body, pulmonary infarction, trauma and debilitating medical conditions. Although spontaneous clostridial pneumonia has been reported previously, close scrutiny of those case reports suggests that most of the patients had a recognised predisposing cause. We report a case of true spontaneous Clostridium perfringens pneumonia complicated by septic shock, pneumothorax and pulmonary necrosis. The patient responded poorly to conventional treatment with benzylpenicillin, and although the addition of metronidazole produced dramatic resolution of the sepsis, lobectomy was required to effect cure. PMID- 8447583 TI - Bilateral subdural haematomas: a rare diagnostic dilemma following spinal anaesthesia. PMID- 8447584 TI - Anaesthesia for thoracoscopy. PMID- 8447585 TI - Return of the phantom. PMID- 8447586 TI - Anaesthesia for Mauriac's syndrome. PMID- 8447587 TI - Allergy testing after uneventful anaesthesia. PMID- 8447588 TI - Simple method for warming fluids for caesarean section. PMID- 8447589 TI - IV or IA lines? PMID- 8447590 TI - Dural tap causing C8 paraesthesia. PMID- 8447592 TI - Detecting arterial puncture while inserting central venous lines. PMID- 8447591 TI - Laparoscopic total fundoplication: anaesthesia and complications. PMID- 8447593 TI - Pin index failure. PMID- 8447595 TI - How safe is blood? PMID- 8447594 TI - Hypokalaemia--is it a common clinical problem? PMID- 8447596 TI - Fit with finger block. PMID- 8447597 TI - Insertion of LMA: thiopentone with topical lignocaine. PMID- 8447598 TI - Tubuloglomerular feedback mechanism. PMID- 8447599 TI - Subdural block. PMID- 8447600 TI - Transfusion: morbidity and mortality. AB - Homologous, and to a significantly lesser extent, autologous blood transfusion is associated with definable and potentially serious risk. The increasing professional and public awareness has led to a critical evaluation of transfusion practices and a change in transfusion philosophy towards optimising transfusion therapy for individual patients. This involves the provision of the safest blood and the minimisation of homologous blood exposure. Autologous blood transfusion is not without risk as misidentification of patient or unit, bacterial contamination and volume overload can occur; consequently, the indications for the transfusion of autologous blood, as per homologous units, must be appropriate to the clinical circumstances. Appropriate transfusion criteria are being developed and lower haemoglobin levels are becoming accepted. Transfusion-related mortality and morbidity data is infrequently reported. Ongoing transfusion surveillance programs have reported adverse reactions in 3.5% of transfusion episodes and fatalities have resulted from ABO-incompatible acute haemolytic transfusion reactions, most commonly with group O recipients of group A or B red cells. A significant number of such deaths are attributable to misidentification of patient or units and are preventable by obsessional attention to clerical details. The risks should be considered in the evaluation of the risk-benefit equation and in the resultant decision to administer blood. PMID- 8447601 TI - Hazards of bacterial contamination of blood products. AB - Post-transfusion bacterial sepsis is infrequent. It is, however, associated with a high mortality due to septic shock. This reflects the release of endotoxin from gram negative bacteria. Lesser transfusion reactions are usually under-reported. These are frequently caused by gram positive bacteria. Gram positive species such as staphylococci and other skin surface organisms may be cultured from platelets stored at room temperature. Typically, gram negative "psychrophyllic" species which survive storage at 4 degrees C are cultured from stored refrigerated blood implicated in transfusion reactions. These include Yersinia enterocolitica, Pseudomonas fluorescens etc. Bacterial contamination of the blood supply can occur via an endogenous or an exogenous source. Endogenous donor bacteraemia due to Y.enterocolitica may be asymptomatic or may follow an episode of gastroenteritis. Exogenous infections occur through some defect in the usual collection practice. Transfusion-acquired syphilis is now extremely uncommon. In the third world, beside the need for effective screening for viral pathogens, infections with protozoa, in particular plasmodia, trypanosoma and leishmania remain a major obstacle to ensuring safe blood supplies. Prevention of transfusion reactions demands rigorous attention to details of collection, storage, reissuing and infusion of blood products, as well as prompt treatment, testing and reporting of suspected reactions. PMID- 8447602 TI - Transfusion transmitted infection: viral and exotic diseases. AB - Viral and other exotic diseases may be transmitted by blood transfusion. These infections include human immunodeficiency virus (HIV), hepatitis viruses (A, B, C, D and E), syphilis, malaria, retrovirus HTLV-1, and cytomegalovirus. Other more exotic diseases which may be transmitted by transfusion of blood or blood components include Chagas' disease (Trypanosomiasis cruzi), Lyme disease (Borrelia burgdorferi), and Jakob-Creutzfeldt disease. Screening procedures currently used in Australian blood banks minimise transfusion-transmitted infection. The risk of acquiring any infection in this manner may be less than 0.1%. PMID- 8447603 TI - Cattlin's bag and Clover's facepiece for nitrous oxide anaesthesia. PMID- 8447604 TI - Adverse reactions to plasma and plasma components. AB - Since the early days of plasma fractionation, plasma and derivatives have been identified as being responsible for a spectrum of mild to life-threatening reactions, but it is increasingly being recognised that plasma and its derivatives may be responsible for a wider range of reactions in recipients and more frequently than is commonly appreciated by clinicians. These reactions may be related to immunological differences between the donor and the recipient, either with the component being antigenic to the recipient or the plasma containing an antibody reacting with a recipient antigen. Secondly, there may be physicochemical characteristics of the plasma component such as temperature, additives, alterations due to preparative process and accumulation of metabolites or cellular release products on storage. All of these may in some patients be responsible for clinically significant reactions. This review presents a broad overview of the clinical presentations of recipient reactions due to plasma or plasma components and their underlying mechanisms. Unless there is an immediate or acute fulminant reaction to the infusion of plasma component, adverse effects of these blood products frequently go unrecognised and untreated. Some of the reactions, if undiagnosed, may have a significant effect on the outcome of the patient. There are also various preventative measures which may be taken in the preparation of blood products or their administration to minimise their potential adverse effects. PMID- 8447605 TI - Leukodepleted blood components. AB - The use of leukodepleted blood components may reduce some adverse effects of transfusion in certain clinical situations. This review outlines the recognised effects of contaminating passenger leucocytes, the value of leukodepleted components in preventing some of these complications, methods of leukodepletion and the current recommendations for use of these components. PMID- 8447606 TI - Blood transfusion related adult respiratory distress syndrome. AB - Adult respiratory distress syndrome (ARDS) is a rare but important complication of blood transfusion because it has a mortality rate of 50-60%. ARDS is characterised by noncardiogenic pulmonary oedema and is often associated with major trauma and/or sepsis. Clinical features include dyspnoea, tachypnoea, chills and extensive crepitations. The pathogenesis has not been elucidated completely and a number of hypotheses have been proposed. Factors which have been implicated include neutrophil sequestration and complement activation, macrophages, metabolites of the arachidonic acid cascade and cytokines, all of which contribute to the amplification of the inflammatory process. In particular, leucoagglutinins have been implicated with blood transfusions. Treatment is generally supportive as specific therapeutic strategies remain largely unproven. PMID- 8447607 TI - Complement (C3, C4) and C-reactive protein responses to cardiopulmonary bypass and protamine administration. AB - Complement activation has been deemed responsible for the damaging effects of cardiopulmonary bypass (CPB) in patients undergoing open heart surgery. We studied C3, C4 and C-reactive protein (CRP) in 22 patients undergoing CPB. In Group 1 (11 patients), protamine was given intravenously and in Group 2 (11 patients), via the aortic root after CPB. Significant decreases were observed in C3 and C4 during CPB in both groups indicating complement activation primarily by the classic pathway. Protamine did not lead to further activation of the complement system. In both groups, C3 levels gradually returned toward baseline within 24 hours but C4 levels were still lower than baseline 24 hours postoperatively. CPB and protamine administration did not cause any significant changes in CRP levels, but CRP increased abruptly 24 hours after operation. Although activation of complement system during CPB is expected to invoke an acute phase response, we conclude that this period is not long enough to induce an increased production of CRP in response to tissue injury or inflammation. PMID- 8447608 TI - Effect of "renal-dose" dopamine on renal function following cardiac surgery. AB - The efficacy of renal-dose dopamine to improve renal function or reduce renal impairment was studied in 52 patients undergoing elective coronary artery bypass surgery. The patients were prospectively randomised in a double-blind fashion to receive dopamine at 200 micrograms/min (group D) or placebo (group P) from induction for 24 hours. Although dopamine improved haemodynamics, there was no effect on urine output at 4 hours (D = 917, P = 1231 ml: P = 0.066); urine output at 24 hours (D = 3659, P = 3304 ml: P = 0.36); creatinine clearance at 0-4 hours (D = 104, P = 127 ml/min: P = 0.27); creatinine clearance on admission to ICU-4 hours (D = 94.8, P = 83.4 ml/min: P = 0.48); creatinine clearance at 20-24 hours (D = 91.2, P = 107 ml/min: P = 0.48); free-water clearance at 0-4 hours (D = 29.6, P = -59.8 ml/hr: P = 0.069); free-water clearance at 20-24 hours (D = 43.2, P = -48.9 ml/hr: P = 0.55). The incidence of transient renal impairment was similar in both groups (D = 36%, P = 50%: P = 0.65). Our study failed to demonstrate that routine prophylactic renal-dose dopamine is associated with improvement in renal function, or with prevention of transient renal impairment in patients undergoing coronary artery bypass surgery. PMID- 8447609 TI - Noninvasive monitoring of tidal volume with an extensometer: laboratory and clinical studies. AB - The extensometer or "rubbery ruler" (RR) is a new torso transducer with potential application in the field of respiratory pattern analysis. This paper determines whether the RR can measure tidal volume over a clinically useful time frame following spirometric calibration. Laboratory testing identified no error or baseline drift during 774,000 controlled stretches. Clinical testing in a variety of patients demonstrated that 96.6% of derived spirometric values were contained within an error range of +15.2% to -16.9% of spirometrically measured tidal volume and that accuracy did not change over a period of one hour. These results are encouraging and suggest that this device merits further investigation. PMID- 8447610 TI - Efficacy of pressure support in compensating for apparatus work. AB - Breathing through an endotracheal tube, connector, and ventilator demand valve imposes an added load on the respiratory muscles. As respiratory muscle fatigue is thought to be a frequent cause of ventilator dependence, we sought to examine the efficacy of five different ventilators in reducing this imposed work through the application of pressure support ventilation. Using a model of spontaneous breathing, we examined the apparatus work imposed by the Servo 900-C, Puritan Bennett 7200a, Engstrom Erica, Drager EV-A or Hamilton Veolar ventilators, a size 7.0 and 8.0 mm endotracheal tube, and inspiratory flow rates of 40 and 60 l/min. Pressure support of 0, 5, 10, 15, 20 and 30 cm H2O was tested at each experimental condition. Apparatus work was greater with increased inspiratory flow rate and decreased endotracheal tube size, and was lowest for the Servo 900 C and Puritan Bennett 7200a ventilators. Apparatus work fell in a curvilinear fashion when pressure support was applied, with no major difference noted between the five ventilators tested. At an inspiratory flow rate of 40 l/min, a pressure support of 5 and 8 cm H2O compensated for apparatus work through size 8.0 and 7.0 endotracheal tubes and the Servo 900-C and Puritan Bennett 7200a ventilators. However, the maximum negative pressure was greater for the Servo 900-C. The added work of breathing through endotracheal tubes and ventilator demand valves may be compensated for by the application of pressure support. The level of pressure support required depends on inspiratory flow rate, endotracheal tube size, and type of ventilator. PMID- 8447611 TI - A comparison between direct and calculated oxygen saturation in intensive care. AB - We investigated the discrepancy between calculated and spectrophotometrically determined oxygen saturation, and the corresponding effect of this difference on calculated oxygen uptake in 46 arterial-venous sample pairs from 28 critically ill patients. The range of discrepancy between the two methods showed limits of agreement (mean +/- 2SD) of -2.26 to +0.70% for arterial samples, and -5.52 to +4.96% for the corresponding venous samples. The effect of this variation on oxygen uptake showed limits of agreement of -43.2 to 36.0 ml/min when the discrepancy between oxygen uptake, calculated using the direct measure of saturation, was compared to that using the derived value. Multiple regression analysis showed that PCO2, temperature and 2,3 diphosphoglycerate were significantly related to saturation discrepancy with an R-squared value of 0.64 (P < 0.0001) for a subgroup of 25 venous samples. The precision of the PO2 electrode was also found to be a major contributory component to the discrepancies, particularly at venous PO2 values. Thus the use of calculated oxygen saturation may result in clinically significant inaccuracies in the assessment of some oxygen flux variables. PMID- 8447612 TI - One hundred sciatic nerve blocks: a comparison of localisation techniques. AB - One hundred sciatic nerve blocks performed for surgery related to lower limb vascular disease were prospectively audited with respect to the techniques used for sciatic nerve localisation and the success rates achieved. Utilising a 22 gauge Quincke point needle, sciatic nerve localisation was performed by initially searching for paraesthesia, followed by the use of a low powered peripheral nerve stimulator. Overall there were 89 successful blocks. Paraesthesia was found in only 44 cases of which 41 were subsequently judged to be successful blocks. A positive response to the nerve stimulator was achieved in 95 cases of which 87 went on to have successful blocks. Our findings suggest that either eliciting paraesthesia or a positive response to the peripheral nerve stimulator carries a high correlation with subsequent successful block, but that the use of the nerve stimulator provides a more consistent and reliable technique for nerve localisation. PMID- 8447613 TI - The influence of adrenaline on postoperative analgesia after subarachnoid morphine. AB - A randomised, double-blind study was conducted to investigate the postoperative effects of subarachnoid morphine, with or without adrenaline, after major gynaecological surgery. Seventy-five women having spinal anaesthesia combined with either sedation or general anaesthesia were randomised to receive subarachnoid morphine 0.25 mg with (group MA) or without (group M) adrenaline 200 micrograms; or normal saline (group C). Groups M (n = 22) and MA (n = 25) differed significantly from control (n = 23) with respect to the quality and duration of postoperative analgesia (P < 0.0002) and to a higher incidence of pruritus (P < 0.02). Groups were similar with respect to the incidence of other postoperative side-effects and respiratory data, although the latter showed a trend to less hypoxaemia in the control group. There was no significant difference in any outcome between groups MA and M. It was concluded that, under the study conditions in a post-gynaecological surgery population, the addition of adrenaline to subarachnoid morphine was of no benefit. PMID- 8447614 TI - Enteral feeding, gastric colonisation and diarrhoea in the critically ill patient: is there a relationship? AB - In this prospective study we aimed to determine whether there is any relationship between enteral feeding, gastric colonisation and diarrhoea in the critically ill patient. Sixty-two critically ill patients from an intensive care unit of a major teaching hospital, who satisfied the usual criteria for enteral feeding, were randomised to receive enteral feeding or not for three days followed by a second randomisation to enterally feed or not for three days. Diarrhoea was recorded and cultures taken of both gastric aspirates and stool. There was no significant difference in the incidence of diarrhoea between the groups. Gastric colonisation was unrelated to feeding practice and to the development of diarrhoea. We conclude that in the critically ill patient, enteral feeding does not cause or promote diarrhoea. PMID- 8447615 TI - Insertion of the laryngeal mask airway--a prospective study of four techniques. AB - The standard insertion technique (ST 0) for laryngeal mask airway insertion was compared to three alternative techniques in 120 patients. The alternative techniques included insertion using the standard approach, but with the cuff either semi-inflated (ST 0.5) or fully inflated (ST 1.0), and a non-standard approach using a back-to-front technique (like a Guedel airway) and with the cuff fully deflated (T 180). Successful insertion was judged by fibreoptic positioning (P < 0.02) and that confirmed that the ST 0 and T 180 were superior to ST 0.5 and ST 1.0 in terms of fibreoptic positioning (P < 0.02) and that insertion with the cuff deflated (ST 0 and T 180) resulted in fewer insertion failures than with the cuff inflated (ST 0.5 and ST 1.0) (P < 0.05). Insertion with the LMA back-to front with the cuff deflated produced similar fibreoptic and functional results to the standard technique. In 23%, however, there was some residual rotation of 25-90% to the coronal plane. PMID- 8447616 TI - Prophylactic paracetamol for analgesia after vaginal termination of pregnancy. AB - Many patients present to day surgery clinics for vaginal termination of pregnancy, a procedure which is frequently complicated by postoperative abdominal pain. We have assessed the efficacy of prophylactic paracetamol 1000 mg given orally shortly before surgery in 834 such patients in a randomised, placebo controlled, double-blind study. Postoperative pain was reported in 35% of patients, with no significant difference between treated and control patients. This negative finding was unexpected and is so far unexplained, given the usual efficacy of oral paracetamol in relieving this type of pain after it has occurred. PMID- 8447617 TI - Optimization of pH for the separation of organic acids in capillary zone electrophoresis. AB - The migration behavior and optimum separation of a set of substituted phenols is presented. A mathematical model that describes mobility in CZE in terms of fundamental constants of each solute (acid dissociation constant Ka, mobility of the dissociated acid microA-) and the pH of the buffer was used to predict the mobility of each solute as a function of pH. The resolution between each peak pair was calculated, and a window diagram of minimum resolution as a function of pH was employed in determining the optimum pH. A comparison of the predicted and actual electropherograms shows the usefulness of this technique. PMID- 8447618 TI - Determination of on-line differential refractive index and molecular weight via gradient HPLC interfaced with low-angle laser light scattering, ultraviolet, and refractive index detection. AB - Gradient ion-exchange chromatography (IEC) was interfaced with a low-angle laser light scattering photometer (LALLS) and ultraviolet (UV) and refractive index (RI) detectors connected in series for on-line determination of the differential refractive index (dn/dc) of proteins and eventually their molecular weights (Mw's). Interfacing of gradient HPLC with a RI detector was made possible by using two isorefractive buffers, which helped generate stable baselines for the LALLS and RI detectors. An optically modified, laser based RI detector was used for determination of dn/dc. On-line determinations of dn/dc required smaller amounts of sample compared to off-line determinations (3-4 mg vs 200 mg). Also, dn/dc could be measured by making one repetitive injection of the sample, if the molar absorptivity of the sample was known. dn/dc values determined on-line were in close agreement with those determined off-line. Additionally, percent recovery of the sample was calculated on-line, and this provided true concentration detected at the UV detector, which was then used for determination of Mw. PMID- 8447620 TI - Performance evaluation of an easily prepared optically transparent carbon film electrode. PMID- 8447619 TI - Spatially resolved temperature measurements in electrophoresis capillaries by Raman thermometry. AB - Local temperatures inside a 75-microns-i.d. capillary under electrophoresis conditions are measured noninvasively with a Raman microprobe. The method is based on the temperature dependence of the water O-H stretch equilibrium between weakly bent and strongly bent hydrogen bonded species. With calibration against a known temperature standard, this technique is shown to be capable of obtaining spatially resolved intracapillary temperature measurements with an accuracy of +/ 1.0 degree C and a precision of +/- 0.1 degree C. Intracapillary temperatures ranging from 25 to 70 degrees C are observed over the range of buffer compositions and electric fields used. Differences between local temperatures and average capillary temperatures are observed at all operating conditions. The difficulty of an accurate theoretical description of heat dissipation under CE conditions is discussed. PMID- 8447622 TI - Transition health officials hear nursing's concerns. Interview by Mandy Mikulencak. PMID- 8447621 TI - AIDS patient care challenges nursing. PMID- 8447623 TI - Computer software available for tracking needlestick injuries. PMID- 8447624 TI - Position statements explore HIV issues. PMID- 8447625 TI - Task force builds foundation for ANA's response to HIV. PMID- 8447626 TI - A day in the life of a nurse. Patients challenge RN to learn more. PMID- 8447627 TI - Long-term AIDS care given from the heart. PMID- 8447628 TI - The new faces of the epidemic. PMID- 8447629 TI - Staff nurses speak out on reform. PMID- 8447630 TI - Living with the epidemic--the tragedy in Africa. PMID- 8447631 TI - States work to combat HIV/AIDS crisis. PMID- 8447632 TI - RN to develop intervention program for African-American women. PMID- 8447633 TI - Mental health care designed for AIDS patients. PMID- 8447634 TI - It's 1993--do you know where your attitude is? PMID- 8447635 TI - Pulmonary TB: an AIDS-defining diagnosis. PMID- 8447636 TI - Autonomy for nursing education threatened in Pa. PMID- 8447637 TI - Membership campaign targets all nurses. PMID- 8447638 TI - Think twice about relying on employer liability coverage. PMID- 8447639 TI - Cover letters: a crucial first contact. PMID- 8447640 TI - Other nurses honored. PMID- 8447641 TI - Time to fight for a single payer system. As I see it. PMID- 8447642 TI - ANA--never a dull moment! PMID- 8447643 TI - HIV positive nurses: caring for our own. PMID- 8447645 TI - Native-American RNs join program to improve tribal health care. PMID- 8447644 TI - Nurses' role essential in HIV education. PMID- 8447646 TI - Nursing classifications recognized by National Library of Medicine. PMID- 8447647 TI - Epidermoid-induced pulsating eye. AB - An otherwise asymptomatic 62-year-old woman had a pulsating but not proptotic eye. Computed tomography showed a low-density mass lesion in the temporal lobe that extended through a defective greater wing of the sphenoid, indented the lateral rectus muscle, and displaced the optic nerve. Magnetic resonance imaging confirmed these findings and showed no enhancement of the lesion by gadolinium. An epidermoid cyst was diagnosed on the basis of its location in the cleavage lines of the temporal lobe, irregular margins, low density by imaging scans, lack of enhancement, and invasion of the orbit. Epidermoid tumors are, therefore, another cause for a pulsating eye. PMID- 8447648 TI - Endophthalmitis caused by nutrient variant streptococci after filtering bleb surgery. AB - Late-onset endophthalmitis after filtering bleb surgery is most often caused by streptococci. We report the first case of endophthalmitis caused by nutrient variant streptococci (NVS), which probably originated from the oral cavity. This patient's vision improved from light perception to 20/80 with intravitreal and systemic antibiotic administration. In late-onset endophthalmitis, NVS can be pathogenic; the laboratory must be alerted to culture specifically for this fastidious bacterium. PMID- 8447649 TI - Posterior vitreous detachment: a possible complication of noncontact tonometry. AB - Two patients who underwent conventional screening noncontact tonometry (NCT) were seen after screening for acute onset of floaters, resulting from posterior vitreous detachment. Neither patient had evidence of retinal holes or tears. This observation suggests that NCT rarely may induce posterior vitreous detachment. PMID- 8447650 TI - Toxoplasmic papillitis as the initial manifestation of acquired immunodeficiency syndrome. AB - Toxoplasmic retinochoroiditis has been reported as the initial manifestation of acquired immunodeficiency syndrome (AIDS). Two authors have described two patients with AIDS and toxoplasmic papillitis. We report the case of a patient with a papillitis of unknown origin in whom the workup found systemic toxoplasmosis and subsequent positive human immunodeficiency virus status. To our knowledge, this is the first reported case of toxoplasmic papillitis as the initial manifestation of AIDS. PMID- 8447651 TI - Central retinal vein occlusion after heart-lung transplantation. AB - We report two cases of central retinal vein occlusion occurring after heart-lung transplantation in young adults. The patients underwent cardiopulmonary bypass during heart-lung transplantation, which may produce systemic hypotension and increased intraocular pressure. In addition, cardiopulmonary bypass is associated with disturbances in hemostasis and alterations in platelet function. Clotting factors frequently are administered during and after transplantation. Systemic hypothermia also is induced during cardiopulmonary bypass. Postoperatively, these patients developed hypertension and hyperlipidemia secondary to the immunosuppressive therapy used to help prevent rejection. It was postulated that these conditions may predispose a patient to having a central retinal vein occlusion. PMID- 8447652 TI - Plasma lipids and lipoproteins in retinopathy of type I (insulin-dependent) diabetic patients. AB - The most important factor associated with the development of diabetic retinopathy is the duration of the diabetes. Studies to examine the relationship of diabetic retinopathy to plasma lipids and lipoproteins have produced conflicting results. We examined the association of background and proliferative retinopathy development with plasma lipid and lipoprotein changes in 78 patients with Type I diabetes. We found significant increases in plasma total cholesterol, low-density lipoprotein (LDL) cholesterol, LDL phospholipid, and high-density lipoprotein (HDL) cholesterol only in patients with proliferative retinopathy. The changes in plasma triglycerides, HDL phospholipid, and apolipoproteins A and B, were not significant. Furthermore, the duration of diabetes and patient age were correlated with both background and proliferative retinopathy. PMID- 8447653 TI - Laboratory diagnosis of keratomycosis: comparative evaluation of direct microscopy and culture results. AB - In a prospective study, we evaluated the sensitivities of direct microscopy using potassium hydroxide 10% wet-mount preparations and culture for definitive diagnosis of keratomycosis in 171 clinically suspected fungal corneal ulcers. Although cultures were positive in 88 eyes (51.46%), the fungus could be demonstrated by KOH preparation in 94.3% (83 of 88) of the culture-proved cases and 93.6% (160 of 171) of the overall eyes. Direct microscopic examination of a KOH wet-mount preparation is a rapid, reliable, and superior technique of laboratory diagnosis. It is particularly important for the early initiation of antifungal treatment in mycotic keratitis. PMID- 8447654 TI - Treatment of retinal detachment in Marfan syndrome. AB - Pars plana lensectomy and vitrectomy were done to treat six eyes with retinal detachment and dislocated lenses in five consecutive patients with Marfan syndrome. In five eyes, the retinas were reattached (follow-up range, 18 months to 4 years). In one eye, the retina redetached ten months after primary surgery and was repaired successfully with pneumatic retinopexy (follow-up, 3 years). PMID- 8447655 TI - Endophthalmitis in intravenous drug abuse. AB - Endophthalmitis usually results from surgical trauma, and it rarely complicates intravenous drug abuse. A case is reported of an intravenous drug abuser who had staphylococcal endophthalmitis. PMID- 8447656 TI - HLA frequencies in Basques in Spain and in neighbouring populations. AB - HLA antigen and gene frequencies at the A, B, and C loci are examined in a sample of 181 Basques and 102 non-Basques in Bilbao, Spain. The most common associations of genes at the A and B loci are as in western Europe generally. The results are compared with gene frequencies in other Basque and non-Basque samples in Spain and France. There is clear distinction in gene frequency between Basques and non Basques, to which the greatest contribution is made by A1 and B35, followed by B7, B8 and B12; and a difference between Basques in France and in Spain, notably in A28, 29, 30 and 31 and B17 and 18. PMID- 8447657 TI - Stature among members of a nineteenth century American Shaker commune. AB - A set of heights of white men, women and children who lived in a Shaker commune near Albany, New York between 1840 and 1865 is analysed. Since the Shakers practiced celibacy, members were recruited from outside the commune, so that their stature to some extent reflects living standards in the antebellum northeast United States. Despite small sample sizes, some conclusions may be stated. Heights among birth cohorts of adult Shaker men fluctuated within a narrow range along the trends of military samples, but were much shorter than military samples. Successive birth cohorts of adult women became generally shorter over the first decades of the century, associated with the influx of very short urbanites. Shaker women, even in relative terms, were much shorter than Shaker men, which may reflect broader sexual differences in net nutrition. Although in weight-for-height terms entering Shaker children were not undernourished, they were shorter than children in samples for somewhat later American populations. Members of both sexes grew taller with a longer duration of Shaker upbringing. PMID- 8447658 TI - Isonymy structure of four Venezuelan states. AB - The isonymy structure of four Venezuelan States-Falcon, Merida, Nueva Esparta and Yaracuy-was studied using the surnames of the Venezuelan register of electors updated in 1984. The surname distributions of 155 counties were obtained and, for each county, estimates of consanguinity due to random isonymy and Fisher's alpha were calculated. It was shown that for large sample sizes the inverse of Fisher's alpha is identical to the unbiased estimate of within-population random isonymy. A three-dimensional isometric surface plot was obtained for each State, based on the counties' random isonymy estimates. The highest estimates of random consanguinity were found in the States of Nueva Esparta and Merida, while the lowest were found in Yaracuy. Other microdifferentiation indicators from the same data gave similar results, and an interpretation was attempted, based on the particular economic and geographic characteristics of each State. Four different genetic distances between all possible pairs of counties were calculated within States; geographic distance shows the highest correlations with random isonymy and Euclidean distance, with the exception of the State of Nueva Esparta, where there is no correlation between geographic distance and random isonymy. It was possible to group counties in clusters, from dendrograms based on Euclidean distance. Isonymy clustering was also consistent with socioeconomic and geographic characteristics of the counties. PMID- 8447659 TI - Age and height as predictors of peak expiratory flow rate in Indian girls. AB - Peak expiratory flow rate (PEF) was measured on 175 healthy Indian girls in the age range 8-18 years with the help of Wright's Peak Flow Meter. PEF was recorded in the post absorptive phase at least 1 h after breakfast. The subjects rested for 0.5 h before the test procedure and tests were carried out between 1000-11000 hrs to avoid diurnal changes. The highest of three recordings was noted as the subject's PEF. PEF, age, height and body weight were correlated with each other and an intercorrelation matrix between these variables has been designed. It was observed, after performing multivariate regression analysis, that age and height are significant predictors of PEF. A multiple linear regression equation and a nomogram have been constructed for predicting PEF from age and height in young healthy Indian girls. PMID- 8447660 TI - Social change, height, and body mass in Victorian youth, 1805-1914. AB - A corpus of height studies from the period 1805-1914 was assembled. In the first of three studies the data were assessed for autocorrelation and for departure from linearity. In the second study, heights indexed to the P50 values identified by Tanner, Whitehouse and Takaishi (1966) were regressed on three economic variables, consecutively, in the presence of three ecological measures. In the third study, an estimate of Quetelet's index (w/h2) was calculated for males in the years 1832-1911. Implications were derived from the analyses. PMID- 8447661 TI - Growth of children in a iodine-deficient area in northern Zaire. AB - In a case-control study all preschool children of 50 villages in an iodine deficient area in northern Zaire were examined for the absence or presence of a goitre. Children with goitre but without obvious signs of cretinism (cases) were maximally matched with a goitre-free child of the same ethnic group, village, sex and age (controls). Anthropometry of cases and controls was compared in order to investigate if endemic goitre is associated with any growth impairment. Surprisingly, between ages 2 and 4 years, children with goitre are taller and heavier, and have a smaller triceps skinfold thickness. Arm circumferences did not differ between cases and controls. Stunting is more prevalent in controls. If manifest cretinism is excluded, goitre is not associated with growth retardation. The higher anthropometric figures in goitrous children remain unexplained. In the absence of any data on the hormonal status of these two groups of children, it can only be surmised that, in iodine-deficient areas, some degree of hypothyroidism negatively influencing growth might be more frequent in non goitrous children than in goitrous ones. PMID- 8447662 TI - Age at menarche from a Biscayan coastal population (Basque Country). AB - Data on menarcheal age were collected by the status quo method on a sample of 894 schoolgirls (9-19 years of age), from the Biscay province coast (Basque Country, Spain). Logit analysis provided a mean age at menarche of 12.75 +/- 0.04 years with a standard deviation of 0.93. The result was compared with data from another previous Basque study. PMID- 8447663 TI - Body composition in old age. PMID- 8447664 TI - Month at menarche: a re-evaluation of the seasonal hypothesis. PMID- 8447665 TI - Allograft skin as an adjunct in the repair of radiation-compromised wound. PMID- 8447666 TI - Systemic dapsone. PMID- 8447667 TI - Keratoacanthoma in Kauai, Hawaii. The first documented incidence in a defined population. AB - BACKGROUND AND DESIGN: A prospective 5-year population-based incidence study was conducted on the island of Kauai, Hawaii, from 1983 through 1987 to investigate the frequency of keratoacanthoma in white residents. RESULTS: A total of 53 residents, 36 men and 17 women, were identified with an initial episode of keratoacanthoma during the 5-year study. The average annual incidence rate per 100,000 Kauai residents, standardized to the US white population, was 144 for men and 73 for women, with a combined rate of 104. The average patient age was 63.5 years. The limbs, particularly the hands and arms, were the most common anatomic site, with the trunk second. Only one patient developed a new subsequent keratoacanthoma, and no recurrent lesions were observed. Three patients had two keratoacanthomas when they first presented, and 13 patients had concurrent skin cancer. Sixty percent (32) of our patients developed skin cancer at one time or another. CONCLUSIONS: We report the first population-based keratoacanthoma incidence rates documented in the United States, which are almost equal to those of squamous cell carcinoma. Keratoacanthoma also shares many common epidemiological features with squamous cell carcinoma, such as increasing incidence in progressively older age groups. PMID- 8447668 TI - Proliferation characteristics of cutaneous squamous cell carcinomas developing in organ graft recipients. Comparison with squamous cell carcinomas of nonimmunocompromised hosts by counting argyrophilic proteins associated with nucleolar organizer regions. AB - BACKGROUND AND DESIGN: Cutaneous squamous cell carcinomas (SCCs) are a frequent complication in organ graft recipients (OGRs). The clinical evolution of these lesions has been a matter of controversy. We studied, by the technique of counting argyrophilic proteins associated with nucleolar organizing regions, the proliferative profile of 11 SCCs developing in six OGRs and compared it with the profile in a group of 18 nonimmunocompromised patients with SCCs. The density of the inflammatory cellular peritumoral infiltrate was also assessed semiquantitatively. RESULTS: The SCCs in OGRs and controls contained similar numbers of argyrophilic proteins associated with nucleolar organizing regions; however, the density of the inflammatory cellular peritumoral infiltrate was much lower in OGRs than in controls (2.00 +/- 0.77 vs 3.17 +/- 0.79). CONCLUSIONS: The proliferative potential of SCCs developing in the setting of iatrogenic immunosuppression does not seem to be different from that of SCC in nonimmunocompromised hosts; however, since metastatic SCCs are known to have a reduced density of the inflammatory cellular peritumoral infiltrate as compared with nonmetastatic cases, SCCs in OGRs could have a higher metastatic potential than similar lesions developing in a control population. PMID- 8447669 TI - Deep penetrating nevus. AB - BACKGROUND: Deep penetrating nevus is a variant of melanocytic nevi with histologic features that may be alarming and can be mistaken for malignant melanoma. We are presenting a review of the clinical findings and the histologic features of deep penetrating nevus in a series of 14 cases. OBSERVATIONS: Deep penetrating nevus occurs most commonly over the acral skin of young adults. Clinically, the lesions were diagnosed as pigmented nevus, blue nevus, or malignant melanoma. Histologically, deep penetrating nevus shows a wedge-shaped lesion extending to the deep dermis and the subcutaneous fat tissue. Nests and fascicles of pigmented melanocytes extended deep at the periphery of blood vessels, nerves, and the cutaneous adnexa. Low-grade cellular atypia is present and mitoses are rare. CONCLUSIONS: Deep penetrating nevus is a variant of benign pigmented nevi with deep dermal and subcutaneous involvement. The pattern should be recognized and differentiated from malignant melanoma. PMID- 8447670 TI - A case of Rothmund-Thomson syndrome with reduced DNA repair capacity. AB - BACKGROUND: Rothmund-Thomson syndrome is an autosomal recessively inherited disease with multiple skin disorders, and little has been known about the cause of the clinical features. We cultured the cells from a patient with Rothmund Thomson syndrome and examined the ultraviolet repair characteristics. OBSERVATIONS: A 5-year-old boy with Rothmund-Thomson syndrome is presented. He has had reticular pigmentation and hypopigmentation on his cheeks, upper aspect of the trunk, palms, and soles since 6 months of age. Cells originating from the patient had reduced unscheduled DNA synthesis, 37% of normal, after exposure to ultraviolet C (predominantly at 254 nm), and they were slightly more sensitive to ultraviolet C than were normal cells in cell ultraviolet survival. CONCLUSION: Such repair deficiency might account for the mild sun sensitivity in early childhood. Heterogeneity in the repair mechanism as well as in clinical features in this syndrome was suggested. PMID- 8447671 TI - Phakomatosis pigmentovascularis type IIb with iris mammillations. AB - BACKGROUND: Phakomatosis pigmentovascularis type IIb is a syndrome in which extensive nevus flammeus is associated with persistent aberrant mongolian spots. Herein, we describe a patient with phakomatosis pigmentovascularis who had numerous iris mammillations that were initially mistaken for the Lisch nodules of neurofibromatosis type I. OBSERVATIONS: A 5-year-old girl with phakomatosis pigmentovascularis type IIb was found to have bilateral melanosis oculi and numerous iris mammillations. The mammillations differed from Lisch nodules in their smaller size, stellate shape, darker color, increased number, and more regular distribution. Similar iris mammillations have been described in patients with melanosis oculi accompanying nevus of Ota. CONCLUSIONS: Patients with phakomatosis pigmentovascularis can present with the clinical manifestations of one or more of the following: Sturge-Weber syndrome, Klippel-Trenaunay syndrome, and melanosis oculi; our patient had clinical features of all three of these entities. In addition, the presence of iris mammillations in this patient can be explained by their known association with melanosis oculi. PMID- 8447672 TI - Familial cold urticaria. Investigation of a family and response to stanozolol. AB - BACKGROUND: Familial cold urticaria is a rare cutaneous and systemic reaction to cold with autosomal dominant inheritance, distinctive clinical features, and unknown pathogenesis. Release of a chymotrypsinlike substance has been postulated. To date, no effective treatment has been reported. OBSERVATIONS: Eight cases from a large family pedigree are described. Three members showed a very favorable response in their cold urticaria, when treated with stanozolol; the response was reproducible. Histologic examination of an early lesion in one case revealed evidence of mast cell degranulation. CONCLUSIONS: The biochemical observations are probably secondary epiphenomena. Correction of a deficiency of an inhibitory protein is a possible mechanism of action of stanozolol as in hereditary angioedema. PMID- 8447673 TI - Clinical pharmacology. PMID- 8447674 TI - Clinical syndromes associated with DNA repair deficiency and enhanced sun sensitivity. PMID- 8447675 TI - Lymphomatoid papulosis and associated lymphomas. How are they related? PMID- 8447676 TI - Skin-associated lymphoid tissue (SALT)-related B-cell lymphoma (primary cutaneous B-cell lymphoma). A concept and a clinicopathologic entity. PMID- 8447677 TI - Telogen effluvium. New concepts and review. AB - BACKGROUND: Telogen effluvium is the result of a perturbation of the hair cycle that is manifest by increased loss of normal club hairs. Although diverse causes for telogen effluvium have been proposed, this article suggests several diverse mechanisms for the first time. OBSERVATIONS: Five different functional types of telogen effluvia are proposed based on changes in different phases of the follicular cycle. These are immediate anagen release, delayed anagen release, short anagen syndrome, immediate telogen release, and delayed telogen release. Diverse causes are confirmed and drug-related telogen effluvia are reviewed. CONCLUSIONS: The five diverse mechanisms proposed for telogen effluvia are generally confirmed and supported by clinical findings. PMID- 8447678 TI - Persistent asymptomatic nodules on the legs. Nodular pretibial myxedema. PMID- 8447679 TI - A widespread hemorrhagic and crusted eruption of recent onset. Pityriasis lichenoides et varioliformis acuta (PLEVA) (Mucha-Habermann disease). PMID- 8447680 TI - An asymptomatic penile lesion. Circular indurated lymphangitis of the penis (CILP) with concurrent syphilis. PMID- 8447681 TI - A pruritic eruption with reticular pigmentation. Prurigo pigmentosa. PMID- 8447682 TI - Iatrogenic Cushing's syndrome in a dog from owner's topical corticosteroid. PMID- 8447683 TI - Systemic sensitization to ethanol by transdermal estrogen patches. PMID- 8447684 TI - Pityrosporum folliculitis and severe pruritus in two patients with Hodgkin's disease. PMID- 8447685 TI - Lichen sclerosus et atrophicus treatment with the 585-nm flashlamp-pumped pulsed dye laser. PMID- 8447686 TI - Plaquelike cutaneous lupus mucinosis. PMID- 8447687 TI - Exfoliative erythroderma resulting from inadequate intake of branched-chain amino acids in infants with maple syrup urine disease. PMID- 8447688 TI - No evidence for a relation between Borrelia burgdorferi infection and old lesions of localized scleroderma (morphea) PMID- 8447689 TI - Plasma viscosity in giant cell arteritis as a predictor of disease activity. AB - Thirty one patients with giant cell arteritis (GCA) receiving standardised prednisolone treatment were followed up for one year with analyses of plasma viscosity, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and fibrinogen concentration. On the day of diagnosis all patients had an increased plasma viscosity and ESR, whereas the concentration of CRP was normal in three patients and fibrinogen concentration and haptoglobin values were normal in one patient. IgG levels were increased in two patients. Plasma viscosity correlated significantly with the ESR, IgG level, and fibrinogen concentration. Laboratory variables in subgroups of patients with GCA proved by biopsy were not different from the whole group of patients with GCA. The follow up showed that CRP normalised faster than the ESR, plasma viscosity, and fibrinogen concentration. Plasma viscosity and the ESR paralleled clinical findings more closely and predicted flare ups better than the other variables. Plasma viscosity had advantages over the ESR for predicting flare ups and in the clinical monitoring of treatment with glucocorticoids. PMID- 8447690 TI - Antinuclear antibodies in routine analysis: the relevance of putative clinical associations. AB - Defined antinuclear antibodies (ANA), such as antibodies to Ro/SS-A, La/SS-B, Sm, and nRNP, are often present in serum samples from patients with systemic lupus erythematosus (SLE) or other connective tissue diseases (CTD). Most data on associations between the presence of these antibodies and defined disease features have been obtained with the use of predefined groups of patients. In this work the issue of disease associations was approached from a different angle: patients suspected of having CTD were selected on the presence of these ANA in their serum samples and clinical data were subsequently scored according to a defined protocol. It was then tried to relate measured ANA and clinical symptoms. No correlation was observed between the presence of antibodies to Ro/SS A and specific clinical symptoms. The presence of antibodies to La/SS-B was associated with the diagnosis of Sjogren's syndrome combined with leukocytopenia. In patients positive for antibodies to Sm a significantly increased incidence of skin lesions, such as butterfly rashes and discoid lesions, was seen, together with signs of myocarditis. Myocarditis was also found to be associated with the presence of antibodies to nRNP. The data presented in this study show that previously reported associations of these ANA with clinical symptoms are not confirmed when unselected patients are used. PMID- 8447691 TI - Possible clearance of effete polymorphonuclear leucocytes from synovial fluid by cytophagocytic mononuclear cells: implications for pathogenesis and chronicity in inflammatory arthritis. AB - A feature common to all forms of chronic inflammatory arthritis, irrespective of the possible underlying cause, is the persistent exudation of large numbers of polymorphonuclear leucocytes (PMNL) into synovial fluid. These cells possess potent degradative enzymes and proinflammatory mediators, and their removal is vital to normal inflammatory resolution. A major route of disposal of extravasated PMNL appears to be programmed cell death (apoptosis), followed by their rapid recognition, and intact phagocytosis, by mature tissue macrophages. Such macrophages, containing PMNL (cytophagocytic mononuclear cells (CPM)), long recognised in synovial fluid as Reiter cells, are commonly found in reactive arthritis, spondyloarthritis, and crystal arthritides, but only rarely in rheumatoid disease. In a retrospective analysis of 187 knee synovial fluid cytospins, the relation between the formation of CPM and the presence of apoptotic (pyknotic) PMNL was investigated. As long as the synovial fluid examined was fresh there was a high correlation between numbers of CPM (as a percentage of macrophages) and pyknotic numbers of PMNL in fluids containing CPM. This suggests that the formation of CPM occurs in vivo and is involved in the disposal of PMNL. Numbers of pyknotic PMNL increased rapidly in stored synovial fluid without a significant change in numbers of CPM, and were highest in synovial fluid which did not contain CPM. The presence or absence of CPM, or their disease associations, could not be explained simply by limiting numbers of macrophages, or apoptotic PMNL in synovial fluid. These findings are consistent with a regulatory role for CPM in synovial fluid, where they may be important in preventing autolysis of PMNL, and thus local tissue damage. PMID- 8447692 TI - Responses of synovial fluid and peripheral blood mononuclear cells to bacterial antigens and autologous antigen presenting cells. AB - The specificity of T cells in the inflamed joints of patients with rheumatoid arthritis (RA) has been the subject of much study. Bacterial antigens are suspect in the aetiology of rheumatic diseases. The responsiveness of the mononuclear cell fraction of peripheral blood and synovial fluid of patients with RA and of patients with rheumatic diseases other than RA to bacterial antigens such as cell wall fragments of the anaerobic intestinal flora, cell wall fragments of Streptococcus pyogenes, intestinal flora derived peptidoglycan polysaccharide complexes, the 65 kilodalton protein of Mycobacterium tuberculosis, and muramyldipeptide was investigated. No significant difference in response was found to all these bacterial antigens in the synovial fluid of patients with RA compared with the responses in patients with other rheumatic diseases. The highest responsiveness in the synovial fluid of the patients with RA was to the streptococcal cell wall fragments and to the 65 kilodalton protein. Higher responses to several bacterial antigens in the synovial fluid of patients with RA were found compared with peripheral blood from the same patient group. The antigen presenting cell population of the synovial fluid in patients with RA and the patients with other rheumatic diseases was found to be stimulatory for autologous peripheral blood T cells even in the absence of antigen. This suggests an important role for the synovial antigen presenting cell in the aetiology of inflammatory joint diseases. PMID- 8447694 TI - Multipoint determination of pressure-volume curves in human intervertebral discs. AB - To gain further insight into the biomechanics of the human intervertebral disc and to determine a potential mechanism for causation and relief of symptoms related to a herniated disc, the pressure-volume relation was determined within the nucleus pulposus. Pressure was measured continuously within the nucleus pulposus in 17 intact lumbar discs from human cadavers by means of a miniature strain gauge at the tip of a size 4 French (1.3 mm) catheter inserted into the nucleus pulposus. The volume of the nucleus pulposus was increased at the slow, continuous rate of 0.034 ml/min by the pump regulated infusion of saline coloured with methylene blue. In 12 unloaded discs, nucleus pulposus pressure rose in a linear fashion (linear r = 0.96) from an initial mean pressure of 174 (SD 81) kPa. The mean rate of pressure rise was 327 (SD 109) kPa/ml volume increase. The peak pressure measured was 550 kPa; this was slightly higher than the capability of the transducer. Similar linear relations were obtained during infusion of saline into five vertically loaded discs fixed at the deformation produced by a 9.1 kg weight. The data define the pressure-volume relation within the disc and show that the nucleus pulposus, surrounded by the relatively inelastic annulus and the solid vertebral end plates, has the properties of a tight hydraulic space in which a large pressure rise will regularly result from a small increase in volume. Presumably the opposite is also true. The data may provide a biomechanical basis for the physiological variation in symptoms related to the disc, and for any benefits obtained from interventions designed to remove disc tissue. PMID- 8447693 TI - Microheterogeneity of alpha 1 acid glycoprotein in rheumatoid arthritis: dependent on disease duration? AB - The microheterogeneity of alpha 1 acid glycoprotein (AGP) was studied using affinity immunoelectrophoresis with concanavalin A (Con A) in serum samples of 43 patients with early rheumatoid arthritis (RA) without clinical features of intercurrent infection. The results were expressed as reactivity coefficients. Disease activity was measured by clinical (Lansbury's joint index, Mallya-Mace activity score) and laboratory (erythrocyte sedimentation rate, levels of soluble interleukin-2 receptor, C reactive protein, and AGP) indices. In contrast with previous reports, suggesting a decrease in AGP-Con A reactivity in patients with RA, high values of AGP reactivity coefficients were found in patients with disease of short duration, which were similar to those found in patients with acute bacterial infections. Conversely, normal or decreased values of AGP reactivity coefficients were found in patients with disease of longer duration. Regression analysis showed a significant relation between AGP reactivity coefficients and disease duration (multiplicative model). No other indices examined were significantly related to disease duration. These results, taken together with previous findings suggesting that cytokines control the glycosylation of acute phase proteins, indicate that differences in the microheterogeneity of AGP in early and longstanding RA reflect differences in cytokine action at different stages of the disease. PMID- 8447695 TI - 6-Thioguanine nucleotide accumulation in erythrocytes during azathioprine treatment for systemic connective tissue diseases: a possible index for monitoring treatment. AB - BACKGROUND: Owing to adverse pharmacokinetics, azathioprine treatment may fail to induce a satisfactory clinical response in systemic connective tissue diseases. The major intracellular cytotoxic metabolites of azathioprine are 6-thioguanine nucleotides (6TGNs). METHODS: To assess whether the erythrocyte accumulation of 6TGN is a clinically applicable index for monitoring azathioprine treatment, erythrocyte accumulation of 6TGN was measured in patients with rheumatoid arthritis (n = 12), systemic lupus erythematosus (n = 7), polyarteritis nodosa (n = 2), myositis (n = 1), or leukocytoclastic vasculitis (n = 1). Ages ranged from 28 to 75 (median 58) years. RESULTS: Erythrocyte accumulation of 6TGN varied among the patients from 20 to 303 (median value 95) nmol/mmol haemoglobin. No significant correlation was found between erythrocyte accumulation of 6TGN and the dose of azathioprine/kg body weight, the age of the patients, the duration of treatment, or the presence of myelotoxicity or hepatotoxicity. The interindividual coefficient of variation (CV) in the erythrocyte accumulation of 6TGN/mg azathioprine/kg body weight was 0.65. The median intraindividual CV in erythrocyte accumulation of 6TGN at an unchanged dose of azathioprine was 0.09 (19 patients; range 0.03-0.27). CONCLUSIONS: The low intraindividual variation compared with the high interpatient variation in erythrocyte accumulation of 6TGN implies that erythrocyte accumulation of 6TGN may be clinically applicable for monitoring azathioprine treatment. Prospective studies are needed to clarify the relation between the erythrocyte accumulation of 6TGN and the clinical response to treatment, and to establish recommendations for dose modifications. PMID- 8447696 TI - HLA antigen familial study in complete Behcet's syndrome affecting three sisters. AB - Behcet's disease is a multisystemic disease affecting most organs. Although a tendency towards an association with a certain genetic type and with HLA-B51 is suspected, the incidence of several siblings with Behcet's disease in a single family is rare. A family, in which three sisters were affected with Behcet's disease, uveitis being the most severe manifestation, was studied. In this family all siblings were B51 positive. Only the female siblings, however, with a positive identical HLA phenotype: A2, A11, B51, B44, Cw6, Cw5, DR4, DRw13, DRw53, DRw52, DQw7, DQw6, developed the disease symptoms, whereas none of the male siblings was affected. PMID- 8447697 TI - Systemic amyloidosis AL with temporal artery involvement revealing lymphoplasmacytic malignancy in a man presenting as polymyalgia rheumatica. AB - A 68 year old man presented with a clinical and biological picture that suggested polymyalgia rheumatica. Temporal artery biopsy disclosed no inflammatory change but massive light chain amyloid deposits in the media. Further exploration showed a malignant lymphoplasmacytic haemopathy with a triclonal gammopathy and a muscular, rectal, and probable cardiac amyloidosis. Cryoglobulinaemia and high concentrations of soluble interleukin 2 receptor (sIL-2R) were also found. This is the fifth case with confirmed involvement of the temporal artery. The especially high sIL-2R concentration was thought to reflect the tumour mass rather than lymphocyte activation. PMID- 8447698 TI - Is measurement of rheumatoid factor isotypes clinically useful? PMID- 8447699 TI - Rheumatic disease following immunotherapy. PMID- 8447700 TI - Synovial fluid T cells in HTLV-I positive RA. PMID- 8447701 TI - False negative results of anticardiolipin antibody test. PMID- 8447702 TI - The gold plated stomach? PMID- 8447703 TI - Cigarette smoking and risk of osteoarthritis in women in the general population: the Chingford study. AB - Previous studies have suggested that smoking might be protective against the development of osteoarthritis (OA) of the knee. A group of 1003 women aged 45-64 years (mean 54.2 years) from the Chingford general population survey were studied to examine the effect of cigarette smoking on the prevalence of radiologically confirmed OA at different sites. Standard anteroposterior radiographs of the hand and knee were available in 985 women. Disease classification was made on the basis of radiological OA and symptomatic radiological OA. Odds ratios were calculated and adjusted for age and body mass index. A total of 463 (46.2%) women were ever smokers compared with 540 (53.8%) non-smokers. Ever smokers had consumed an average of 14.9 cigarettes a day for a mean of 25.7 years. For radiological OA of the distal interphalangeal joint (DIP) (140 women), proximal interphalangeal joint (40 women), carpometacarpal joint (160 women), and knee joint (118, women) there was no reduced risk of OA in ever smokers. In the small number of subjects with generalised OA (22 women) there was a non-significant 40% reduction of radiological OA in ever smokers (odds ratio 0.63; 95% confidence interval 0.24 to 1.68). Results were similar for subjects with radiographic clinical OA, except the DIP joint which showed a positive association between smoking and Heberden's nodes (odds ratio 2.02, 95% confidence interval 1.89 to 3.42). Results were similar when analysed using current smokers against never smokers. These results do not support an inverse association between cigarette smoking and OA in women. A possible inverse relation with the small subgroup of women with generalised OA and an effect of cigarettes on disease severity cannot, however, be discounted. PMID- 8447704 TI - Association of radiographic changes of osteoarthritis, symptoms, and synovial fluid particles in 300 knees. AB - Associations between compartmental distribution of radiographic changes of osteoarthritis (OA), individual features of OA (joint space loss, sclerosis, cyst, osteophyte; each scored 0-3), and presence of synovial fluid calcium particles (calcium pyrophosphate dihydrate (CPPD) crystals identified by polarised light microscopy and other calcium particles by alizarin red positivity (ARP) were sought in 300 osteoarthritic knees (178 patients; mean age 72, range 33-96 years). Patients whose knees were symptom free as well as those with symptoms were included. Osteoarthritis of two or three compartments but not unicompartmental OA was associated with the presence of CPPD or ARP. Involvement of any compartment (not just patellofemoral), and higher mean scores for both total and individual osteoarthritis changes (except cysts) was associated with CPPD and ARP; CPPD, but not ARP, was associated with symptoms: knees reported as having symptoms had higher mean total OA scores. Femoral cortical erosion, found more often in women, was associated with higher mean total OA score at the patellofemoral compartment but not with the presence of particles. Attrition, remodelling, and chondrocalcinosis (each scored as present or absent) occurred more often in knees with CPPD. Age did not correlate with any aspect of the OA score. This study confirms the association of calcium particles with the process of OA. Unlike previous studies confined to symptomatic knees, a radiographic pattern specific to CPPD ('pyrophosphate arthropathy') did not emerge. PMID- 8447705 TI - A new medical diagnosis of Adolf Hitler. Giant cell arteritis-temporal arteritis. PMID- 8447706 TI - Optimal dose for starting and maintaining low-dose aspirin. PMID- 8447707 TI - Reserpine and the medical marketplace. PMID- 8447708 TI - Increased prevalence of Helicobacter pylori antibodies among nurses. AB - BACKGROUND: Numerous studies have suggested that Helicobacter pylori infection in asymptomatic subjects is transmitted from person to person. Its prevalence is higher in the institutionalized setting. If that is the case, persons involved in patient care should have a higher prevalence of the infection. METHODS: We estimated the prevalence of H pylori antibodies among groups of asymptomatic medical and nursing staff and compared them with volunteer blood donors of similar age and sex. RESULTS: One hundred fifty-eight nurses and aides, 59 residents, 46 senior medical students, and 22 senior nursing students were enrolled in this study. Serum samples were tested for IgG antibodies against H pylori by enzyme-linked immunosorbent assay. Sixty-two (39%) of 158 nurses were found to be positive for antibodies to H pylori compared with 114 (26%) of 441 specimens from the blood donor group. Within the youngest age group (20 to 34 years), 13 (25%) of 51 nurses were positive for H pylori antibodies compared with 19 (13%) of 143 age-matched serum samples from the blood donor group. Within the middle age group (35 to 49 years), 32 (39%) of 83 nurses were positive for H pylori antibodies vs 43 (26%) of 167 age-matched blood donors. In the oldest age group (> 50 years), 17 (71%) of 24 nurses were positive for H pylori antibodies compared with 52 (40%) of 131 age-matched blood donors. Twenty-three (27%) of 86 nurses with 1 to 15 years of occupational exposure were positive for H pylori antibodies compared with 40 (56%) of 72 nurses with more than 15 years of occupational exposure. CONCLUSIONS: Nurses have an increased prevalence of H pylori antibodies that is significantly higher than the comparable prevalence of volunteer blood donors and is evident in the youngest age group. In addition, the increased prevalence is related to a longer duration of patient exposure in the nursing group. PMID- 8447709 TI - Reducing antipsychotic drug use in nursing homes. A controlled trial of provider education. AB - OBJECTIVE: In the United States, 20% or more of nursing home residents receive antipsychotic drugs, primarily for the behavioral manifestations of dementia. This high level of use of drugs with substantial toxicity has engendered a strong and persistent controversy and recently has led to explicit regulatory measures to curtail use (Omnibus Budget Reconciliation Act of 1987). We developed and tested a comprehensive program to reduce antipsychotic use through education of physicians, nurses, and other nursing home staff. The primary elements of the program were instruction in use of behavioral techniques to manage behavior problems and encouragement of a trial of gradual antipsychotic withdrawal. DESIGN: In a nonrandomized controlled trial, the program was implemented (beginning in August 1990) in two rural Tennessee community nursing homes with elevated antipsychotic use; two other comparable homes were selected as concurrent controls. PATIENTS: Throughout the study 194 residents were in the education homes and 184 were in the control homes. Residents in both groups of homes had comparable demographic characteristics and functional status, and each group had a baseline rate of 29 days of antipsychotic use per 100 days of nursing home residence. MAIN OUTCOME MEASURES: The primary end points were postintervention changes in administration of antipsychotics and other psychotropic drugs, use of physical restraints, and frequency of behavior problems. RESULTS: Days of antipsychotic use decreased by 72% in the education homes vs 13% in the control homes (P < .001). No significant changes were noted in the use of other psychotropic drugs in either group. Days of physical restraint use decreased 36% in the education homes vs 5% in the control homes (P < .001). Behavior problem frequency did not increase in either group, even among the 48% of baseline antipsychotic users in the education homes who had antipsychotic drug regimens discontinued for 3 or more months. CONCLUSIONS: The educational program led to a substantial reduction in antipsychotic use with no increase in the frequency of behavior problems. This suggests that for many antipsychotic drug users benefits may be marginal and that programs to reduce such drug use among the 250,000 US nursing home residents receiving these drugs should have high priority. PMID- 8447710 TI - Limits of patient autonomy. Physician attitudes and practices regarding life sustaining treatments and euthanasia. AB - BACKGROUND: In making decisions about life-sustaining medical interventions, respect for patient autonomy has been widely advocated, yet little is known about what variables may compete with a physician's ability to honor patient requests in clinical situations. We investigated physician attitudes and behaviors about end-of-life decisions by means of a questionnaire that posed five hypothetical scenarios in which an elderly, competent, terminally ill patient made a request that, if agreed to by the physician, could result in the patient's death. METHODS: We surveyed 392 physicians in Rhode Island and asked them to decide (1) whether or not they would comply with a specific patient request, (2) the justifications they used in making their decision, and (3) whether they had been approached with such a request in their clinical practices. RESULTS: Two hundred fifty-six physicians (65%) responded. Of the respondents, 98% agreed not to intubate the patient in the face of worsening respiratory failure. Eighty-six percent agreed to give the patient a dose of narcotics that could cause respiratory compromise and death to treat his pain adequately. Fifty-nine percent agreed, once the patient was intubated without hope of coming off the respirator, to turn the respirator off. Nine percent agreed to give the patient a prescription for an amount of sleeping pills that would be lethal if taken all at once. Only 1% agreed to give the patient a lethal injection. When they complied with patient requests, physicians cited patient autonomy as the principle most important to their decision making. Physicians who would not comply with patient requests also, paradoxically, often cited this principle but agreed with it less strongly; others cited concerns about the ethical nature of the request, legal questions, and the perception that they were "killing the patient." Sixty-five percent of respondents had been asked by patients to turn off a respirator, and 12% had been asked to administer lethal injections. Twenty-eight percent of respondents indicated that they would comply with requests for lethal injection more frequently if such an action were legal. CONCLUSIONS: Difficult clinical decisions regarding potentially life-prolonging measures are commonly heard in clinical practice. Physicians value the concept of patient autonomy but place it in the context of other ethical and legal concerns and do not always accept specific actions derived from this principle. PMID- 8447711 TI - Developing a resident assistance program. Beyond the support group model. AB - BACKGROUND: A program designed to identify and address specific evolving needs of residents throughout their first year has been implemented in our department of medicine. The average annual participation is 55 residents. The program includes a detailed and structured curriculum with topics and activities aimed at improving nonclinical skills that help residents function effectively during residency. METHODS: The program was developed based on a careful analysis of problems reported by graduating residents. It consists of 12 sessions in which the residents are presented with typical difficult situations they are likely to encounter during the year. At the end of each session they are provided with strategies to help them deal with the problems or even prevent problems in some cases. An important aspect of the program is the training and utilization of senior residents as group leaders. RESULTS: Eighty-five percent of the first-year residents have actively participated in the program since July 1989 despite its voluntary nature. Participants reported that the program greatly accelerated their adaptation and helped them function more effectively in the system. Senior residents recognized benefits for their professional development as well. CONCLUSIONS: The collective wisdom of past generations is often not effectively communicated to post-graduate year 1 residents. They are left to reinvent the wheel, not always with the best results. As a consequence, a great deal of stress that can be minimized is introduced into the training process. This program shows promise as an effective mechanism to deal with these challenges. PMID- 8447712 TI - Lymphatic abnormalities in human filariasis as depicted by lymphangioscintigraphy. AB - BACKGROUND: Investigation into filarial lymphedema has been hampered by the lack of a simple, safe, and easily repeated test to image the peripheral lymphatic system. Recent refinements in radionuclide lymphangioscintigraphy have established this noninvasive technique as the initial procedure of choice for visualizing lymphatics. Accordingly, we applied lymphangioscintigraphy to patients with filariasis and, for purposes of interpretation, compared the findings with those in patients with non-filarial lymphedema. METHODS: Thirty three patients with classic symptoms or signs consistent with acute or chronic filariasis underwent lymphangioscintigraphy, and the findings were compared with those in five patients without lymphatic dysfunction and in 50 other patients with primary or secondary lymphedema without exposure to filariasis. RESULTS: As in patients with nonfilarial lymphedema, scintigraphic abnormalities in the 33 patients with filariasis included delayed or absent tracer transport of the radiotracer (25 patients), tortuous and bizarre deep lymphatics (seven patients), dermal diffusion (15 patients), retrograde tracer flow (six patients), and faint or absent regional nodal visualization (14 patients). Even in patients with long standing filarial lymphedema, peripheral trunks were often visualized (at least in part), and regional nodes and more central lymphatics sometimes filled after light exercise. In some of the latter patients, however, discrete lymphatic trunks were not detected. CONCLUSION: Lymphangioscintigraphy is a simple, safe, reliable, noninvasive method with which to examine the peripheral lymphatic system, including truncal and nodal abnormalities, in endemic populations with occult and overt lymphatic filariasis. PMID- 8447713 TI - Comparison of two noninvasive screening tests for renovascular hypertension. AB - OBJECTIVE: To compare and contrast the diagnostic accuracy rates of two newer noninvasive screening tests for renovascular hypertension, the most common curable cause of secondary hypertension. PATIENTS AND METHODS: One hundred fifty patients, thought to have a high probability of renovascular hypertension by established clinical criteria, underwent both the captopril challenge test and the renal scintigram with angiotensin-converting enzyme inhibitor, while on their usual antihypertensive regimen except angiotensin-converting enzyme inhibitors. If the result of either test was abnormal, angiography was undertaken, followed immediately by angioplasty (if a stenosis was found) or by renal vein renin determinations. Patients whose blood pressures were lower 6 to 12 weeks after a revascularization procedure (surgery or angioplasty) were diagnosed as having renovascular hypertension. RESULTS: Of the 150 patients, 100 underwent angiography, and 59 had renal artery stenosis. Of 53 patients who had surgery (n = 21) or angioplasty (n = 32), 51 had lowered blood pressures compared with before the procedure. Sensitivity and specificity of the tests were as follows: renal scintigram with angiotensin-converting enzyme inhibitor: 92% and 91% (all patients) and 92% and 80% (only patients with angiograms); captopril challenge test: 76% and 82% (all patients) and 76% and 58% (only patients with angiograms). Little difference in accuracy rates was observed in subgroup analyses in patients with chronic renal impairment, previous diuretic or beta-blocker therapy, or bilateral renal artery stenosis. CONCLUSIONS: In selected, treated patients with a high probability of renovascular hypertension, the renal scintigram with angiotensin-converting enzyme inhibitor was a more accurate noninvasive screening test than the captopril challenge test. Noninvasive screening tests for renovascular hypertension can help to identify patients who should undergo angiography and often predict success after revascularization. PMID- 8447714 TI - Adenine phosphoribosyltransferase deficiency with renal deposition of 2,8 dihydroxyadenine leading to nephrolithiasis and chronic renal failure. AB - Homozygous adenine phosphoribosyltransferase deficiency is a genetic defect that is associated with 2,8-dihydroxyadenine urolithiasis. Since the prevalence of the heterozygous state is found in 0.4% to 1.2% of the population, it is surprising that more cases of 2,8-dihydroxyadenine urolithiasis have not been reported. Herein we describe a patient with complete adenine phosphoribosyltransferase deficiency with 2,8-dihydroxyadenine urolithiasis leading to chronic renal failure. Gene sequencing revealed that the patient is a compound heterozygote. One of the mutations (a T insertion between bases 346 and 347) has been encountered before, but the second (a G-to-A substitution at base 1356) has not been previously reported. Possible explanations for the unexpected rarity of 2,8 dihydroxyadenine urolithiasis are discussed. PMID- 8447715 TI - Hepatitis E as a cause of acute non-A, non-B hepatitis. AB - Hepatitis E seems to be responsible for most epidemics of non-A, non-B hepatitis in developing countries. While hepatitis E is not endemic in the United States, it should be considered in the differential diagnosis of the traveler with non-A, non-B hepatitis. We describe a patient with acute hepatitis E, confirmed by serologic testing, after recently returning from India and discuss current knowledge about the pathogenesis, clinical features, and diagnosis of hepatitis E. PMID- 8447716 TI - CD8 T cells in human immunodeficiency virus infection. PMID- 8447717 TI - Is the magnesium content of nuts a factor for coronary heart disease? PMID- 8447718 TI - A 'rash' of toxoplasmosis. PMID- 8447719 TI - Angiotensin-converting enzyme inhibitor-induced cough. PMID- 8447720 TI - Comparing Pneumocystis carinii pneumonia prophylactic regimens. PMID- 8447722 TI - Microsomal N-oxygenation of adenine to adenine 1-N-oxide. AB - During investigations on the N-oxygenation of adenine (1) the enzymatic formation of adenine 1-N-oxide 3 was demonstrated for the first time. The identity of this metabolite was confirmed by its chromatographic behaviour and UV-spectrum recorded after HPLC separation. Adenine 1-N-oxide (3) and similar oxygenated derivatives of adenine were synthesized as reference substances. The enzymatic formation of 3 exhibits the typical characteristics of a reaction catalysed by microsomal mono-oxygenases. In induction experiments, an increase in the rate of formation of 3 after pretreatment with phenobarbital was observed. A participation of those isoenzymes of the cytochrome P-450 enzyme system which can be induced by phenobarbital is assumed. PMID- 8447721 TI - The hypolipidemic effects of 2-furoic acid in Sprague-Dawley rats. AB - 2-Furoic acid was shown to be effective in lowering both serum cholesterol and serum triglyceride levels significantly in rats with an elevation of HDL cholesterol level at 20 mg/kg/day orally. LDL receptor activity was reduced in hepatocytes, aorta foam cells, small intestinal epithelium cells and fibroblasts. HDL receptor activity was elevated in the rat hepatocytes and small intestinal cells. These activities were correlated with inhibition of acyl CoA cholesterol acyl transferase activity. Neutral cholesterol ester hydrolase activity was elevated in rat hepatocytes and human fibroblasts. Thus, 2-furoic acid appears to interfere directly with activity of intracellular enzymes rather than affecting high affinity-mediated lipoprotein membrane receptors. In vivo treatment with 2 furoic acid led to reduction in the liver and small intestine ATP dependent citrate lyase, acetyl CoA synthetase, acyl CoA cholesterol acyl transferase, sn glycerol 3-phosphate acyl transferase, phosphatidylate phosphohydrolase and heparin induced lipoprotein lipase activities. 2-Furoic acid reduced biliary cholesterol levels but the agent increased bile salts which are lithogenic. Acute toxicity studies in mice suggest that the agent has some hepatic toxicity effects. The LD50 was relatively low at 250 mg/kg IP in mice. PMID- 8447723 TI - Terephthalic acid in Sprague-Dawley rats as a hypolipidemic agent. AB - Terephthalic acid at 20 mg/kg/day in lowered serum cholesterol and triglyceride levels in rats. The cholesterol content was lowered in the lipoprotein fractions. The effects of the agents on de novo lipid synthesis showed that similar enzymes were affected in rat liver and small intestinal mucosa cells as when compared to in vitro tissue culture cells from rats and humans, e.g. reduction of acyl CoA cholesterol acyl transferase and elevation of neutral cholesterol ester hydrolase activities suggest that net cholesterol esters deposition in foam cells should be reduced and plaque growth should be slowed. The suppression of LDL receptor binding and degradation by the drug suggest that less apoB lipoproteins are taken up by peripheral tissues. The elevated HDL receptor binding and internalization in the liver suggest that the drug accelerates cholesterol return to the liver. Additional studies show that cholesterol and bile acid secretion in the bile is elevated. However, the bile acids secreted are not lithogenic. Acute toxicity studies show that the agent appears to be safe in rodents. Two observations of increased serum alkaline phosphatase levels and increased liver vacuolation suggest some alteration of hepatic cell morphology, which requires further investigation. PMID- 8447724 TI - Decrease of plasma large, light LDL (LDL1), HDL2 and HDL3 levels with concomitant increase of cholesteryl ester transfer protein (CETP) activity by probucol in type II hyperlipoproteinemia. AB - The effects of 12 week probucol treatment on plasma lipoprotein subfraction levels and on lecithin: cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activities in type II hyperlipoproteinemia were investigated. Plasma VLDL-TG, VLDL-apoB, VLDL-apoCII and VLDL-apoCIII concentrations were not changed by probucol, but VLDL-TC and VLDL-PL levels were slightly reduced. Probucol slightly reduced plasma IDL-TC, but not IDL-TG, IDL-PL and IDL-apoB levels. Plasma large, light LDL (LDL1)-TC, LDL1-PL, LDL1-apoB levels were decreased significantly by 28.5 +/- 20.1% (p < 0.001), 18.1 +/- 18.8% (p < 0.01) and 23.3 +/- 19.1% (p < 0.001) by probucol treatment while LDL1-TG concentration was unchanged. Absolute amounts of plasma small, heavy LDL(LDL2) TC, LDL2-TG, LDL2-PL and LDL2-apoB levels remained unchanged but percent increases of LDL2-TC and LDL2-apoB were statistically significant (p < 0.05). 2 16% gradient polyacrylamide gel electrophoresis demonstrated the diminution of LDL of large size by probucol treatment. Probucol markedly reduced plasma high density lipoprotein levels. The reductions of HDL2-TC, HDL2-TG, HDL2-PL and HDL2 apoAI concentrations were 36.2 +/- 25.4% (p < 0.001), 25.8 +/- 36.9% (p < 0.01), 34.4 +/- 23.8% (p < 0.001) and 35.6 +/- 28.4% (p < 0.001). Probucol significantly decreased plasma HDL3-TC, HDL3-PL and HDL3-apoAI amounts by 17.4 +/- 22.9% (p < 0.01), 18.3 +/- 20.8% (p < 0.01) and 19.8 +/- 27.9% (p < 0.01) without change of HDL3-TG level. The decrease of HDL2 level was more marked than that of HDL3 level. Probucol did not change LCAT activities. Probucol significantly stimulated CETP activities from 126.6 +/- 50.6 units to 172.8 +/- 40.2 units by 12 week treatment (p < 0.001). We concluded that probucol decreased plasma LDL1, HDL2 and HDL3 amounts and made them triglyceride-rich with the concomitant increase of CETP activities. PMID- 8447725 TI - Ethanol induced hypertension in rats: reversibility and role of intracellular cytosolic calcium. AB - This study examined the reversibility of chronic ethanol induced increase in systolic blood pressure, elevated platelet cytosolic free calcium and aortic calcium uptake in rats and the effect of a calcium channel blocker on these changes. Twenty-four male Wistar-Kyoto rats, age 7 weeks, were divided into 4 groups of 6 animals each. Animals in group I were given water and group II, III and IV, 5% ethanol in drinking water for the next 7 weeks. Systolic blood pressure in the ethanol treated rats was significantly higher (p < 0.01) than in controls after 1 week and remained higher. After 7 weeks, group I was continued on water, group II on ethanol, group III was continued on ethanol but with the addition of verapamil 5 mg/100 ml in their drinking water and group IV was returned to normal drinking water for the next 7 weeks. After 14 weeks, systolic blood pressure, platelet cytosolic free calcium and aortic calcium uptake was significantly higher (p < 0.01) in rats given ethanol for 14 weeks and also in rats given ethanol for 7 weeks followed by water for 7 weeks as compared to controls. These two groups also showed smooth muscle cell hyperplasia with some thickening of the wall and narrowing of the lumen in small arteries and arterioles of kidney. Verapamil given to the ethanol treated rats normalized their blood pressure, platelet cytosolic free calcium, aortic calcium uptake and attenuated renal vascular changes. Discontinuation of ethanol treatment for 7 weeks did not reverse the hypertension or the adverse renal vascular changes in ethanol induced hypertensive rats. PMID- 8447726 TI - Glucose effects on oxygen consumption by the arterial wall. AB - The effect of both D- and L-glucose on the rate of oxygen consumption in rat aorta was determined. Oxygen uptake (V02) was found to decrease when the concentration of D-glucose in the medium was increased, with the same effect being found when L-glucose, rather than D-glucose, was used. Based on these results, it would appear that the decrease in the vascular wall oxygen consumption which results from increased glucose levels is not due to a metabolic effect since one of the isomers (D) is metabolized and the other (L) is not. It is suggested, instead, that these results may be be due to a change in the diffusion of oxygen. Possible implications for atherogenesis are also discussed. PMID- 8447727 TI - Artificial light and early-life exposure in age-related macular degeneration and in cataractogenic phototoxicity. PMID- 8447728 TI - Macular pigment epitheliopathy in retinopathy of prematurity. PMID- 8447729 TI - Indapamide therapy and posterior subcapsular cataract: is there a causal relationship? PMID- 8447730 TI - Recovery from severe visual loss in optic neuritis. PMID- 8447731 TI - Save the optic nerve. PMID- 8447732 TI - Duplication of the lens, hourglass cornea, and cornea plana. PMID- 8447733 TI - Bilateral ciliochoroidal detachments after valsalva maneuver. PMID- 8447734 TI - How many Americans are uninsured? PMID- 8447735 TI - A new guideline for patients with cataract. PMID- 8447736 TI - Whimsy or progress. How can we tell? PMID- 8447737 TI - Cryotherapy for retinopathy of prematurity. 3 1/2-year outcome for both structure and function. PMID- 8447738 TI - Informed consent. AB - Under the law of informed consent, physicians must disclose to patients certain information about their medical condition and potential courses of treatment, and must obtain their consent to proceed. This article delineates the basic standards that govern such disclosure, with special reference to legal cases that have dealt with ophthalmic concerns. It concludes by discussing a number of special issues that have recently arisen in this area. PMID- 8447739 TI - Informed consent and medical ethics. AB - Informed consent is based on a shared decision between physician and patient, with the physician understanding the relevant values of the patient and the patient understanding the nature of the disease and intervention, including risks and benefits. Informed consent has developed rapidly since it was introduced in the 1950s, reflecting recent changes in the practice of medicine that respect the increase of patient autonomy. The purpose of the written consent form is to document that a process of informed consent has taken place. It is generally agreed that all surgical as well as research procedures require written consent. For certain nonsurgical procedures, the decision regarding obtaining written consent will consider both the risk involved for the patient and the general community standard. Informed consent serves as an important symbol of a physician patient relationship that adheres to the valued principles of medical ethics. PMID- 8447740 TI - Is informed consent needed for fluorescein angiography? AB - Fluorescein angiography is a common diagnostic procedure. Questions have been frequently raised as to whether explicit informed consent is needed for this procedure and what form such consent should take. Review of existing legal concepts indicates that the need for explicit consent varies from state to state, but that the trend is to require an explicit discussion of risks, benefits, and alternatives. Documentation of such information can adequately range from a brief, written notation in the patient's chart to a complete, separate form. PMID- 8447741 TI - Current patterns of intraocular gas use in North America. AB - A 1987 survey of 365 members of the Retina and Vitreous societies revealed that use of long-acting intraocular gases was both widespread and frequent. However, despite the expanded use of intravitreal gases and the stated intention of the Food and Drug Administration to approve premarket applications for use of sulfur hexafluoride and perfluoropropane, there are still limitations in the ready availability of these substances. Therefore, we conducted another survey to determine current patterns of intraocular gas use. The results indicate that more surgeons are using long-acting gases. The data also demonstrate the selective use of pneumatic retinopexy with geographic pockets of increased retinopexy use in California and Florida. Finally, 100% of respondents now indicate that they consider the use of sulfur hexafluoride and perfluoropropane to be a standard of care. PMID- 8447742 TI - Long-term results of sutureless phacoemulsification with implantation of a 7-mm polymethyl methacrylate intraocular lens. AB - In an attempt to minimize postoperative astigmatism while retaining the advantages of implanting intraocular lenses with large optics, sutureless phacoemulsification with implantation of a 7-mm polymethyl methacrylate intraocular lens was performed through a modified scleral tunnel in 100 consecutive patients. Visual and keratometric results, as well as complications, were recorded during a follow-up period of 12 months. Average uncorrected visual acuity improved from 20/153 before surgery to 20/66 as early as 1 week after surgery. Average best corrected visual acuity improved from 20/86 before surgery to 20/39 as early as 1 week after surgery. No significant changes in visual acuity were recorded thereafter. The absolute value of keratometric astigmatism was not increased significantly at any postoperative examination time. The induced cylinder shifted from 1.26 diopters x 74.40 degrees at 1 week to 1.22 D x 1.50 degrees at 1 month after surgery, without further relevant changes thereafter. Mean (+/- SD) endothelial cell loss was 7.2% +/- 6.1% at 1 month and 12.2% +/- 5.4% at 6 months after surgery. Corneal thickness was not increased significantly at any postoperative examination time. Implantation of intraocular lenses with large optics through a scleral tunnel allows quick visual rehabilitation as well as early stability of refraction. PMID- 8447743 TI - Multicenter trial of cryotherapy for retinopathy of prematurity. 3 1/2-year outcome--structure and function. Cryotherapy for Retinopathy of Prematurity Cooperative Group. AB - Cryotherapy for Retinopathy of Prematurity Cooperative Group Reports from the 3- and 12-month follow-up examinations in the Multicenter Cryotherapy for Retinopathy of Prematurity trial indicated a beneficial effect of cryotherapy in the treatment of severe retinopathy of prematurity. This report provides results from the 3 1/2-year follow-up examination on 92% of the 256 survivors from the original cohort of 291 infants in the randomized trial. Functional outcome was evaluated by masked assessment of letter acuity using the HOTV crowded letter test and grating acuity using the Teller Acuity Card procedure. Structural outcome was evaluated by physician's assessment of retinopathy of prematurity residua in the posterior pole. All three outcome measures showed a reduction in unfavorable outcomes in treated vs control eyes: 46.6% vs 57.5% (P < .01) for letter acuity, 52.4% vs 65.6% (P < .001) for grating acuity, and 26.1% vs 45.4% (P < .001) for posterior pole status. These results support the long-term efficacy and safety of cryotherapy in the treatment of severe retinopathy of prematurity. PMID- 8447744 TI - Vision in stage 5 retinopathy of prematurity after retinal reattachment by open sky vitrectomy. AB - Performing vitrectomy in stage 5 retinopathy of prematurity is controversial, partially due to limited anatomical and poor reported visual results. Fifty-five eyes of 50 patients whose retinas were reattached by open-sky vitrectomy in stage 5 retinopathy of prematurity and who were followed up for more than 12 months were analyzed retrospectively to ascertain clinical factors that may influence visual outcome. Vision was evaluated by preferential looking. Visual ability to discriminate stationary objects was obtained in 32 (58.2%) eyes, 18 (32.7%) had motion perception, and five (9.1%) had light stimulus perception. Although visual acuities were relatively low, they were useful to these patients. Age at the time of vitrectomy and the shape of the retinal detachment were found to be important factors in predicting visual prognosis. PMID- 8447745 TI - Interferon-associated retinopathy. AB - Interferon alfa is used to treat various systemic disorders and recently has been suggested as a possible treatment for choroidal neovascularization. We report 10 cases of retinal ischemia associated with the use of interferon alfa for various illnesses. The retinal findings include cotton-wool spot formation, capillary nonperfusion, arteriolar occlusion, and hemorrhage. The retinal complications may sometimes be reversible when treatment is stopped. Our findings emphasize the need to have patients who are receiving interferon alfa therapy monitored for these retinal complications, which may rarely be associated with permanent loss of vision secondary to closure of retinal capillaries. PMID- 8447746 TI - Chorioretinal folds. A comparison of unilateral and bilateral cases. AB - We retrospectively reviewed the records, photographs, and fluorescein angiograms of patients with chorioretinal folds to compare features of unilateral and bilateral involvement. We studied 78 eyes of 54 patients and found that 30 (56%) of these patients had unilateral folds and 24 (44%) had bilateral folds. No significant difference was found in comparing visual acuity, refractive error, age, or race in the unilateral vs the bilateral cases. There were significantly more women in the bilateral group (P = .043). The frequency of causes of unilateral cases differed from bilateral cases, but this could not be statistically proven owing to our small sample size. This analysis contains the largest number of chorioretinal folds reported in the literature, and is the first attempt to compare unilateral and bilateral cases. PMID- 8447747 TI - Central serous chorioretinopathy and pregnancy. AB - BACKGROUND AND OBJECTIVE: Fourteen cases of central serous chorioretinopathy in pregnancy had been reported before this study was conducted. These cases have suggested a nonwhite predominance. Subretinal fibrinous exudates have been seen in 90% of the patients, compared with fewer than 20% of patients in typical (nonpregnant) central serous chorioretinopathy. No case has recurred outside of pregnancy, to our knowledge, and there have been no reports of subsequent pregnancies uninvolved by this disorder. These findings led us to collect our cases of central serous retinopathy in pregnancy because our experience differed from that of previous reports and provides additional new information. DESIGN: Case series. SETTING: The Wilmer Institute Retinal Vascular Center, Baltimore, Md. PATIENTS: Questionnaires sent to retinal faculty and fellows and a review of files revealed four patients, all included herein, with central serous chorioretinopathy presenting during pregnancy. RESULTS: All four patients were white. Three patients had subretinal fibrinous exudates and/or precipitates. All experienced resolution of the serous detachment near the end of the pregnancy or within the first few months after delivery. Only one patient had a subsequent pregnancy, and this was not complicated by the presence of central serous chorioretinopathy. One other patient experienced a recurrence 2 1/2 years after her last pregnancy. CONCLUSIONS: There may be no racial predominance in the development of central serous chorioretinopathy in pregnancy. Subretinal fibrinous exudates are quite common, independent of race. The uninvolved subsequent pregnancy suggests that recurrence in the context of pregnancy is not inevitable. This disorder may recur outside of pregnancy. PMID- 8447748 TI - Evaluation of baseline-related suprathreshold testing for quick determination of visual field nonprogression. AB - OBJECTIVE: To evaluate a commercially available means of baseline-related suprathreshold examination designed to detect visual field worsening. DESIGN: Patients for whom results of a baseline series of static-threshold visual field examinations were available underwent both a second static-threshold examination (full-threshold strategy; average time, 15 minutes) and a baseline-related suprathreshold examination ("fast-threshold" strategy; average time, 5 minutes). RESULTS: Most of the 1702 points examined were apparently unchanged from baseline, showing with either method only the degree of variation expected from the measurement inconsistency (short-term fluctuation). For points that did show a change, the changes shown by the two methods were correlated. Change in the field as a whole, represented by a cluster of locations showing deterioration, was evident more frequently with the standard testing strategy: 11 of 37 field examinations showed deterioration by both methods and an additional 11 examinations showed deterioration by the full-threshold method only. CONCLUSIONS: Each examination method identified pointwise changes not detected by the other, the combined effect of false-positive errors (imperfect specificity) and false negative errors (imperfect sensitivity) with each of the two methods. The findings relating to clusters could represent a better sensitivity of the full threshold method in detecting visual field deterioration, a better specificity of the suprathreshold method, or both. PMID- 8447749 TI - Methazolamide-induced skin eruptions. AB - To our knowledge, this is the first histopathologic report of skin eruptions due to oral methazolamide. From the four cases studied, we conclude that there are at least two histopathologic types: one is characterized by perivascular lymphocytic infiltrate with a vacuolar alteration at the dermoepidermal junction, the other by perivascular eosinophils, lymphocytes, and scattered mast cells. There also seem to be at least two patterns of skin eruptions: one maculopapular and the other urticarial. The type of skin eruption and the histopathologic type appear to be related. PMID- 8447751 TI - Bacterial endophthalmitis following sutureless cataract surgery. AB - We examined a patient who developed group G streptococcal endophthalmitis following phacoemulsification with intraocular lens implantation and sutureless wound closure. Pathologic examination of the enucleated globe 1 month after surgery revealed an intense suppurative reaction centered in the anterior chamber and an open surgical wound filled with fibrinopurulent granulation tissue. Inadequate draping, a high number of instruments passing into and out of the eye during surgery, and wound testing for water tightness with viscoelastic substance in the eye were observed on a videotape of the surgery. PMID- 8447750 TI - Miliary toxoplasmic retinitis in acquired immunodeficiency syndrome. AB - A unique pattern of bilateral miliary retinitis due to ocular toxoplasmosis developed in a patient in the late stages of acquired immunodeficiency syndrome. Results of serologic tests for toxoplasmosis remained negative throughout the clinical course of his ocular disease. The retinitis was unresponsive to a brief course of anti-toxoplasmosis therapy. At autopsy, the histopathologic material was consistent with toxoplasmic retinitis and the DNA polymerase chain reaction was positive for toxoplasmosis. Recognition of this pattern of retinitis is important in the appropriate treatment of immunosuppressed patients with retinitis. PMID- 8447752 TI - Intrinsic stability of 'self-sealing' unsutured cataract wounds. AB - Many operative and postoperative factors can influence cataract wound stability and postoperative astigmatism. The final outcome is fundamentally dependent on the intrinsic biomechanical stability of the corneal dome in the presence of the wound. We determined the stability of the central and peripheral cornea with computer-assisted topographic analysis of six freshly enucleated human globes. Self-sealing, unsutured, scleral tunnel wounds 4.0 mm in length were dissected, with widths varying from 1.4 to 6.0 mm. Intraocular pressure was elevated in 5-mm increments from 15 to 40 mm Hg without measurable topographic change in the visual axis or superior cornea. We conclude that these long scleral tunnel wounds do not necessarily destabilize the cornea within the usual range of intraocular pressure. Postoperative-induced astigmatism is therefore due to other operative and postoperative factors. Some of these factors may be identifiable with this model and controlled or eliminated. PMID- 8447753 TI - Mannitol, dextromethorphan, and catalase minimize ischemic damage to retinal pigment epithelium and retina. AB - We studied the recovery of retinal pigment epithelium and retinal function after 80 minutes of pressure-induced ischemia in rabbits. Just before restoring circulation, we gave intravenous mannitol (an osmotic agent and free-radical scavenger), dextromethorphan (an N-methyl-D-aspartate receptor antagonist), or catalase (an antioxidant enzyme). Mannitol has not previously been shown to be protective for retinal or retinal pigment epithelial ischemia. At 24 hours after reperfusion, the electroretinogram b-wave was reduced to 37% of preischemic amplitude in untreated eyes, but it recovered to 67% to 80% after treatment with all three agents. The c-wave was replaced by a negative slow PIII response in control eyes and in seven of 12 catalase-treated eyes, but it recovered by 58% to 82% in the remaining catalase-treated eyes and all the mannitol- and dextromethorphan-treated eyes. Histologic examination confirmed that retinal pigment epithelium as well as retina had been damaged by the ischemia. The effects of mannitol seem of special interest, since the drug has a dual mechanism of action and is clinically available. PMID- 8447755 TI - Photographically documented access of tear film to the anterior chamber through a leaky filtering bleb. PMID- 8447754 TI - Collagen shields exacerbate ulceration of alkali-burned rabbit corneas. AB - OBJECTIVE: To determine the impact of collagen shields on ulceration of rabbit corneas after alkali burn. METHODS: After a 60-second 2N sodium hydroxide burn to rabbit corneas, 24-hour collagen shields were placed on the corneas daily for 21 days; control corneas did not receive collagen shields. The extent of corneal ulceration was documented daily for 21 days by slit-lamp examination of treated and control eyes. Three separate studies were performed using collagen shields from two commercial sources. RESULTS: In the three studies, corneas in the collagen shield-treated eyes began to ulcerate sooner than those in the control group; the corneas in collagen shield-treated eyes also began to perforate sooner. At 21 days after alkali injury, the mean (+/- SE) corneal ulceration score in the collagen shield-treated rabbits was 4.1 +/- 0.17 (descemetocele formation) compared with 2.7 +/- 0.28 (midstromal ulceration) in controls. This difference was significant at P < .005. CONCLUSION: Collagen shield treatment results in marked acceleration of corneal ulceration and perforation after alkali injury. PMID- 8447756 TI - A releasable scleral-flap tamponade suture for guarded filtration surgery. AB - Postoperative complications of filtering surgery are generally associated with overfiltration. We describe a technique that employs an externalized releasable suture in partial-thickness filtering surgery. This suture acts as a tamponade on the anterior surface of the scleral flap, assisting in maintenance of anterior chamber depth during the early postoperative period. After using this technique, anterior-chamber depths preoperatively and 1 day after surgery were compared in 35 phakic patients. A mean (+/- SD) decrease in anterior chamber depth of 4.6% +/ 12% was found on the first postoperative day. One patient had iridocorneal apposition. The mean intraocular pressure 1 day after surgery was 7.0 +/- 7.0 mm Hg, with one patent having an intraocular pressure of 28 mm Hg. This "tamponade suture" appears to be useful in maintaining the anterior chamber depth in the early postoperative period while permitting satisfactory filtration. PMID- 8447757 TI - Frequency-specific aspects of the auditory brainstem response threshold elicited by 1000-Hz filtered clicks in subjects with sloping cochlear hearing losses. AB - The frequency specificity of the ABR threshold evoked by a 1000-Hz filtered click was determined in subjects with sloping cochlear hearing losses, both high- and low-frequency in character. The results show that the ABR threshold evoked by this stimulus is low-frequency specific. The standard error in estimating the 1000-Hz pure-tone threshold (PTT) is 10.4 dB, which equals that for estimating the 3000-Hz PTT from the routinely used click-evoked ABR threshold. The ABR threshold evoked by a 1000-Hz filtered click can therefore be regarded as an accurate tool to predict the pure-tone hearing loss at 1000-Hz. In comparison with the ABR threshold evoked by a click masked with 1590-Hz high-pass noise, the ABR threshold evoked by a 1000-Hz filtered click has a larger dynamic range, yields a larger number of useful responses and is less time consuming. For clinical low-frequency-specific ABR threshold assessment, the 1000-Hz filtered click is therefore preeminently useful. PMID- 8447758 TI - Frequency specificity of human distortion product otoacoustic emissions. AB - The amplitudes and growth functions of distortion product otoacoustic emissions (DPOE) at 2f1-f2, elicited by two primary tones f1 and f2 with a constant frequency ratio f2/f1 = 1.23 and varying geometric mean values 1, 1.5, 2, 4, 6 and 8 kHz, were measured for 25 normal subjects and 50 patients with sensorineural hearing loss. Partial correlations between DPOE amplitudes and auditory thresholds (0.25 to 8 kHz, half-octave steps) were examined. The amplitude of DPOE evoked by low-intensity primary tones (at or below 62 dB SPL) was strongly correlated only with the auditory threshold at their mean frequency, and DPOE disappeared for local hearing losses larger than about 30 dB. Moreover, DPOE amplitudes did not depend on the basal cochlear state. Confounding effects of middle ear transmission and aging were not significant in this set of experiments. When elicited by higher intensities of primary tones (72 dB SPL), DPOE exhibited a more complex and non-local behavior, and their sensitivity to hearing loss decreased. These results suggest that when low-intensity primaries are used, DPOE patterns provide frequency-specific information on the local cochlear state. PMID- 8447759 TI - Normative data for 40-Hz event-related potentials to 500-Hz tonal stimuli in young and elderly subjects. AB - Recordings of 40-Hz event-related potentials (ERPs) were obtained in 81 young subjects (18-40 years) and in 20 elderly subjects (60-77 years) with hearing normal for their age. The stimuli were 500-Hz logons. The first negative peak (N1) of the response was analyzed. With increasing intensity the amplitude of the responses increased and the latency decreased for all subjects. The 40-Hz ERP was obtained within 10 dB of the behavioral threshold for more than 80% of the population under study. The N1 was prolonged in latency and enhanced in amplitude in the older subjects. No differences were found between young and elderly subjects regarding binaural interaction, or in responses elicited by ipsi- and contralateral stimulation. From the clinical point of view, the 40-Hz ERP recordings of young and elderly subjects are similar. PMID- 8447760 TI - Loudness adaptation in children. AB - Simple loudness adaptation was measured for a steady tone presented alone at 10 dB SL; contralaterally induced adaptation was measured for a steady tone in one ear accompanied by an intermittent tone in the contralateral ear; ipsilaterally induced adaptation was measured for a tone increased intermittently by 15 dB. The method of successive magnitude estimation revealed no differences between 12 adults and 36 children from 9 to 14 years of age in the amounts of adaptation over a 3-min exposure. A second set of experiments with a new group of 20 adults and 20 children used a Bekesy tracking procedure to reach similar results. Unlike Karja [Acta Oto-Laryngol 1968; (suppl)241:1-56], who found significant adaptation in only 5 of 29 children and much adaptation in most adults, we found considerable adaptation in children as well as in adults. PMID- 8447761 TI - Impaired speech perception in noise in patients with a normal audiogram. AB - Patients with normal hearing acuity but complaining of impaired speech perception in noisy conditions were submitted to a test battery including the measurement of the speech reception threshold in noise and central auditory tests. In 95% of the cases the complaint was corroborated by an abnormal speech reception threshold (SRT) in noise. Central auditory tests were abnormal in 65% of the patients. Auditory brainstem-evoked potentials were measured in some of these patients and showed normal results in almost all cases. No specific relationship could be found between an elevated SRT in noise or an abnormal central test result. PMID- 8447762 TI - Clinical use of BOBCAT: testing reliability and validity of computerized pure tone audiometry with noise-exposed workers, children and the aged. AB - An investigation was conducted to determine the feasibility of implementing computerized audiometry in various clinical groups, using the Battery of Basic Computerized Audiometry Tests (BOBCAT). Reliability, validity and speed of execution were assessed as a function of hearing loss in a group of noise-exposed workers. Children and the aged were also included to represent potentially 'more difficult-to-test' patients due to fluctuating attention, motivation and/or response behavior. Children were aged 7.5-12 years; seniors, 65-80 years. Reliability was assessed by calculating reliability coefficients between air conduction pure-tone thresholds (0.5, 1, 2, 3, 4 and 6 kHz) obtained under two test modalities namely, computerized audiometry and conventional testing performed by a small panel of trained examiners. Both procedures followed ANSI S3.21 1978 standards. Content validity was measured using measures of central tendency and correlations. Coefficients of reliability remained equally high across frequencies regardless of degree of hearing loss and group. As well, group means and correlations between conventional and computerized audiometry indicated that the two methods measured pure-tone hearing sensitivity with the same degree of accuracy; that is, within +/- 0.5 dB. Finally, speed of execution was found to be slower using BOBCAT, in particular with noise-exposed workers. This finding was interpreted as evidence that trained examiners have used shortcuts when they expect consistent and/or unbiased response behavior. PMID- 8447763 TI - Electrical tinnitus suppression: frequency dependence of effects. AB - Electrical stimulation through a round window electrode has been evaluated in 9 patients with unilateral deafness and severe tinnitus. Three subjects were permanently implanted with positive long lasting results. Analysis of the threshold of sound perception, tinnitus suppression and auditory discomfort levels as a function of current frequency revealed the advantage of low frequency stimulation. In 2 patients the loudness of electrically evoked sound perception was balanced against tones in the hearing ear. Our results can be interpreted as indicating that processes other than auditory masking are responsible for electrical tinnitus suppression. PMID- 8447764 TI - Gentamicin uptake by cochlear hair cells precedes hearing impairment during chronic treatment. AB - Immunodetection of gentamicin (GM) was carried out on surface preparations of the whole organ of Corti from cochleas of guinea pigs treated daily with GM at a dose of 60 mg/kg/day and sacrificed at the end of different treatment periods. Cochlear function was determined just before sacrifice, 24 h after the last injection. Threshold elevations, mainly at high frequencies, were noted only after 10-14 days of treatment. However, the presence of GM was observed much earlier, as early as after the second injection, and specifically in the sensory hair cells. GM labelling was essentially observed in the outer hair cells (OHC) and increased from the apex to the base of the cochlea and from the third to the first row of OHC. GM labelling of inner hair cells was less pronounced and was observed only after the 8th day of treatment. These observations demonstrate that GM specifically enters and accumulates in the sensory hair cells and that the uptake precedes the development of functional and cellular damage which may result from a long-term intracellular cytotoxic action of the molecule. PMID- 8447765 TI - Developmental disturbances of permanent teeth following trauma to the primary dentition. AB - The topographic relationship of the apices of the primary teeth to the permanent tooth germs explains the potential for possible developmental disturbances of the permanent teeth after injuries to their predecessors. The anatomical, histologic and clinical aspects of permanent tooth malformation following trauma to the primary teeth are described. One hundred and fourteen children with originally 255 traumatized primary teeth have been re-examined (with an average period of 5.1 years after the trauma) to assess any developmental disturbances of the corresponding permanent teeth. Twenty-three per cent of partially or completely erupted permanent teeth showed developmental disturbances. The most frequent malformation was enamel hypoplasia including enamel discoloration and/or enamel defects. The highest prevalence of developmental disturbances of permanent teeth was found after intrusive injuries of primary teeth. PMID- 8447766 TI - Multiple supernumerary premolars: their occurrence in three patients. AB - The occurrence of supernumerary teeth in the premolar regions of three patients is reported. Of the 20 supernumerary teeth identified, 16 had crowns which resembled premolars and may thus be considered to be supplemental premolars, while the remainder were conical in shape. The delayed development of the supernumerary teeth in the premolar region supports the hypothesis that these teeth were part of a post-permanent dentition. The eruption of six of the eight supernumerary teeth in the 30-year-old patient demonstrated that given time some of these teeth can erupt into the dental arch. PMID- 8447767 TI - Apicectomy of posterior teeth--a clinical study. AB - Studies evaluating periapical surgery of posterior teeth are relatively few. A retrospective study of 32 apicectomies on posterior teeth using both clinical and radiographic means yielded a success rate of 62 per cent. There were five cases (16 per cent) of failure, the majority of which presented as delayed infection between three and six months following surgery. Post-surgical review of at least six months is recommended. Anatomical considerations for posterior tooth apicectomy and the necessity for retrograde fillings are discussed. PMID- 8447768 TI - The assessment of apical leakage of root-filled teeth by the electrochemical technique. AB - Since its inception by Jacobson and von Fraunhofer in 1976, several studies have used the electrochemical method to assess the leakage occurring around root canal fillings. This study has examined aspects of the electrochemical technique and the effects that this test method may have on leakage results. The findings have raised concerns about the application of the technique. It is evident that electrochemical leakage testing over 30 days can influence the electrochemical leakage reading at 30 days and may influence the linear dye penetration recorded at 30 days. It is suggested that testing for electrochemical leakage should not precede the assessment of linear dye penetration. PMID- 8447769 TI - Acrylic resins reinforced with woven highly drawn linear polyethylene fibres. 3. Mechanical properties and further aspects of denture construction. AB - Previous work has established the feasibility of producing acrylic denture bases reinforced with layers of highly drawn linear polyethylene fibres in a woven form. This paper reports on the mechanical properties of the system, including the effect of water conditioning. It is confirmed that substantial improvements in impact strength can be obtained by the incorporation of the polyethylene fibres in woven form. The fibre/resin integration within the dentures has also been studied by optical microscopy. It was found that delamination may occur during some processing stages and steps are suggested to avoid this problem. PMID- 8447770 TI - The effect of post adaptation in the root canal on retention of posts cemented with various cements. AB - This laboratory study compared the retention of prefabricated posts in well fitting and loose-fitting post canals using different cement materials. Eighty three human teeth were prepared for post placement. One of zinc phosphate cement, polycarboxylate cement, glass ionomer cement or resin cement was used to cement each post in place. A tensile force was applied to remove each post and the separation force was recorded. Posts cemented with the resin cement were the most difficult to dislodge. Posts cemented into loose-fitting canals exhibited greater resistance to dislodgment than posts cemented into well-fitting canals irrespective of the type of cements used. PMID- 8447771 TI - The effect of dentine conditioning with polyacrylic acid on the clinical performance of glass ionomer cement. AB - There is equivocal laboratory evidence that pretreating (conditioning) dentine with poly(acrylic acid) (PAA) increases the bond strength of glass ionomer (polyalkenoate) cement; however, this has only been tested clinically to a limited extent. Forty Class V abrasion lesions were restored with glass ionomer cement; 20 with PAA conditioning and 20 without. Restorations were assessed after one year for marginal staining on a continuous linear rating scale. There was slightly more marginal staining around restorations in the group not conditioned with PAA, and one restoration from this group was partly lost. However, the difference in the clinical performance between the restorations in the two groups was neither clinically nor statistically significant. PMID- 8447772 TI - The development of the dental high-speed air turbine handpiece. Part 1. AB - The high-speed air turbine handpiece is currently used for most dental cutting procedures and has been in widespread use for more than thirty years. Although reports of its historical background have been previously published these have not dealt with all relevant developments and some inconsistencies exist. The history of the development of turbines and their application in dental cutting systems from the late 19th century to the present day is now reviewed. An historical account of the recognition of benefits that may accrue from rotary cutting at increased speeds is given and the various attempts that have been made to design equipment capable of high speeds are discussed. Consideration is given to the development of non-rotary cutting devices, as is the failure of these adequately to replace the air turbine handpiece for routine work. It is concluded that the air turbine handpiece will continue to hold a leading position in the field for some years to come but that future improvements would be facilitated by the development of an understanding of the theoretical aspects of its behaviour. PMID- 8447773 TI - 1993--and where is the recovery? PMID- 8447774 TI - The NSW dentists advertising regulations. PMID- 8447775 TI - The ADA and Colgate-Palmolive. Collusion? Conspiracy? Or, corruption? PMID- 8447776 TI - Choice of toothbrush. PMID- 8447777 TI - Managing the HIV positive patient in general practice. AB - As HIV infection increases in the community it will become increasingly necessary for general practitioners to be involved in the care of these patients. The author resolves some of the doubts GPs may have about their ability to provide primary care to patients with HIV infection. PMID- 8447778 TI - Management of sexually transmissible disease. Part 1. AB - The appearance of AIDS and recent diagnostic and treatment advances has forced the medical profession to become more sophisticated in approaching sexually transmitted diseases. Effective prevention and quality care are fundamental to a sexual health consultation. Obtaining an accurate history on which to base prevention counselling is essential. Treatment of syphilis has not changed in recent years and is not included in this article. PMID- 8447779 TI - STDs and the overseas traveller. AB - Although most HIV and STD patients acquire their infections in Australia there is an increase in the numbers diagnosed with these infections after international travel. Risks to the sexual health of the travellers and their subsequent partners are discussed and suggestions made for minimising risks. PMID- 8447780 TI - Sexually acquired herpes in general practice. AB - The lifelong nature of sexually acquired herpes and its tendency to recur create psychological distress out of all proportion to the actual physical discomfort. Good management rests on a sympathetic and open approach on the part of the clinician. Case histories highlight management issues. PMID- 8447781 TI - Syphilis and gonorrhoea. Current thinking. AB - Syphilis and gonorrhoea have become much less common in urban areas in the past decade, although syphilis is still very prevalent among Aborigines. Considerable unnecessary morbidity from these conditions occurs because of deficiencies in management of infected individuals or their sex partners. PMID- 8447782 TI - Common misconceptions and pitfalls in STDs. Part 1. PMID- 8447783 TI - Urethral discharge in men. AB - Urethral discharge in men is usually associated with sexually transmitted disease. The authors present an overview of likely organisms involved, their clinical course and most appropriate treatment. PMID- 8447784 TI - Common misconceptions and pitfalls in STDs. Part 2. AB - The author explains the pitfalls that can make the treatment of STDs difficult in general practice. In this, the second section of his article, he describes the treatment of bacterial vaginosis, chlamydia, syphilis, gonorrhoea and Hepatitis B and C and other STDs. PMID- 8447785 TI - Management of sexually transmissible disease. Part 2--Viral infections. AB - The management of viral infections, including human immunodeficiency virus (HIV), human papilloma virus (HPV) and herpes simplex virus (HSV), is constantly evolving and should be the domain of all general practitioners. This article reviews current ideas in the treatment of these diseases. PMID- 8447786 TI - Are clinical trials in general practice ethical? AB - The uncertain effect on the doctor-patient relationship is often a stumbling block for many practitioners deciding whether to participate in a clinical trial. In this article, the authors explore some of the ethical issues facing doctors and patients and some of the safeguards that are in place to protect both parties as the trial proceeds. PMID- 8447787 TI - Practice management--warts and all. AB - A recent survey, part of a Practice Management Study, asked 100 doctors how their businesses were going. From the responses, it was evident that there were many areas of concern, including working long hours looking after patients; no time for the family; the accountant does the tax, but that's all; and accountants, solicitors and consultants are too expensive. This article sets out some of the issues raised in the survey. PMID- 8447788 TI - Advocacy, guardianship and the GP. AB - Australians have come to realise that they have a right to access high quality health care through their general practitioner. It is essential that people with cognitive impairments through intellectual disability, psychiatric disorders, senility or brain damage are not denied equity of access through their inability to seek medical attention. Those who cannot make reasonable decisions or who cannot understand and give legal consent to operative procedures may need to have a guardian appointed to protect their rights. In other situations an advocate may be appointed if the person's rights are in jeopardy. The general practitioner is often the first person to become aware of the needs of disabled people and is well placed to intervene to ensure the protection of their rights. This includes the right to good health care. PMID- 8447789 TI - A case of unilateral painful eye. AB - A 24 year old man presented with a painful eye that had been treated empirically with steroid drops. The case is presented to illustrate that before prescribing steroid eye drops, a definitive diagnosis must be reached and this often requires the services of an ophthalmologist. PMID- 8447790 TI - Dr Peter Graham. A champion of rural doctors. AB - A commitment to country general practice and a determination to retain a broad based approach to it has resulted in Peter Graham's involvement in establishing recognition for the skills and training needed by country doctors. By continuing to embrace new skills and techniques he has remained in a medical sense 'a man for all seasons'. PMID- 8447791 TI - Patient education. Ingrowing toenails. PMID- 8447792 TI - Current issues in the treatment of hyperlipidaemias. AB - Following the Consensus Conference on Hyperlipidaemia in Canberra in October 1991 that reviewed the evidence for lipid lowering and its effect as primary and secondary prevention of coronary heart disease PBS guidelines for the use of diet and drugs in management of hyperlipidaemia have been promulgated. The guidelines are summarised in this paper. PMID- 8447793 TI - Reflections on Colquhoun. AB - 'Reflections on Colquhoun' is an interesting twist as it provides an indepth look at our popular regular scribe. AFP is grateful to a colleague who has provided this paper. PMID- 8447794 TI - Pain in the face. PMID- 8447795 TI - Trichotillomania. PMID- 8447796 TI - Where are GPs heading? PMID- 8447797 TI - Influenza--the need for vaccination. PMID- 8447798 TI - Age, circadian rhythms, and sleep loss in flight crews. AB - Age-related changes in trip-induced sleep loss, personality (n = 205), and the pre-duty temperature rhythm (n = 91) were analyzed in crews from various flight operations. Eveningness decreased with age (subjects aged 20-30 were more evening type than subjects over 40). The minimum of the baseline temperature rhythm occurred earlier with age (earlier in subjects aged 30-50 than in subjects aged 20-30). The amplitude of the baseline temperature rhythm declined with age (greater in subjects aged 20-30 than in subjects over 40). Average daily percentage sleep loss during trips increased with age. Among crewmembers flying longhaul flight operations, subjects aged 50-60 averaged 3.5 times more sleep loss per day than subjects aged 20-30. These studies support previous findings that evening types and subjects with later peaking temperature rhythms adapt better to shift work and time zone changes. Age and circadian type may be important considerations for duty schedules and fatigue countermeasures. PMID- 8447799 TI - Multicultural factors in the space environment: results of an international shuttle crew debrief. AB - There is increasing interest and concern about the multicultural and multinational factors which might negatively affect adjustment and performance of Space Station Freedom (SSF) crews, living and working for long periods of time in the space environment. To begin identifying potential problem areas, a crew debrief questionnaire (called an "International Crew Debrief") was mailed to U.S. astronauts who flew on Shuttle missions between 1981-1990 with one or more crewmembers from other countries. There were 20 U.S. astronauts who flew on international space missions; 9 of these responded to the questionnaire, for a return rate of 45%. There were 42 incidents reported: 9 in the preflight period; 26 inflight; and 7 in the postflight period. Most of these incidents were rated as having a low or medium impact, but five of the inflight incidents were rated to have a "high" mission impact. A number of causes for the problems were listed, and are discussed. Debrief respondents provided useful and timely recommendations on preflight training which may help facilitate the integration of multinational crews, and prevent multicultural or multinational factors from interfering with mission operations. PMID- 8447800 TI - Computerized task battery assessment of cognitive and performance effects of acute phenytoin motion sickness therapy. AB - Phenytoin was previously evaluated as an efficacious anti-motion sickness therapy in more than 24 individuals. To be effective, this short-term, novel therapy requires serum levels in the anticonvulsant range; therefore, it became imperative that the effects of phenytoin upon cognition and performance be quantified. Each subject was tested on a performance battery (Criterion Task Set) on two occasions while on either phenytoin treatment or placebo for subsequent statistical comparison. We evaluated 23 subjects with phenytoin serum levels ranging from 8.9 to 23.9 micrograms/L. While subjects with the higher serum levels consistently reported subjective side effects, there was no statistically significant degradation of sensory, cognitive, or performance capabilities compared to placebo. PMID- 8447801 TI - Effect of task complexity on mental performance during immersion hypothermia. AB - The effect of task complexity on the decrement in mental performance during immersion hypothermia was studied. Psychometric tests of varying length and complexity were administered: 1) prior to cold water immersion (baseline); 2) soon after immersion to the neck in cold (8 degrees C) water but prior to any decrease in core temperature; and 3) after 55 to 80 min of immersion when core temperature had decreased 2-4 degrees C. Results indicated that tests placing relatively minimal cognitive demands on individuals, such as auditory attention, the Benton visual recognition test and forward digit span, were unaffected by either initial cold water immersion or central cooling. On the other hand, tests requiring relatively greater mental manipulation and short term memory (i.e., backward digit span) or processing and analysis (i.e., Stroop test) showed a slight improvement upon cold water immersion (perhaps related to increased arousal and/or learning) but a significant decrement following central cooling of 2-4 degrees C. Thus, relatively simple tasks were unaffected by central cooling, whereas more complex tasks were adversely affected. Cold water immersion itself did not interfere with performance of any tasks. Central nervous system cooling probably interferes with mental processing although discomfort and/or the physiological and physical effects of cold on the neuromuscular aspects of speech, required for responses to some of the tasks, may also affect performance. PMID- 8447802 TI - Magnetic resonance imaging evaluation of lower limb muscles during bed rest--a microgravity simulation model. AB - Head-down (-6 degrees) bed rest, a microgravity simulation model in humans, leads to muscular atrophy of the lower limbs. Magnetic Resonance Imaging (MRI) at 0.5 tesla was performed at 1 year intervals on the same six volunteers (except one) before and after 1 month bed rest. Three of the six subjects were daily exposed in a lying position to LBNP (lower body negative pressure), a countermeasure to cardiovascular deconditioning (LBNP group). The groups were exchanged the second year. After bed rest, the quadriceps of the thigh lost uniformly 11% of its cross section area (CSA) and the triceps of the leg 10.5%, with 12.8% lost from the deeper soleus versus 8.5% from the gastrocnemius (p < 0.05). LBNP produced no effect on these changes. The MRI signal intensity of muscles exhibited a trend toward higher values after bed rest although without statistical significance. MRI allowing for noninvasive and reliable quantification of muscle fibers of the lower limbs is an excellent procedure for the assessment of muscle disuse and countermeasures. PMID- 8447803 TI - Cardiovascular responses to upright tilt at a simulated altitude of 3,700 m in men. AB - To examine the effects of high altitude on cardiovascular responses to orthostasis, 11 healthy males were tested at a 10-min passive 70 degrees head-up tilt at sea level and at a simulated high altitude of 3,700 m. During the control period in the supine position, heart rate and forearm blood flow were higher at high altitude (p < 0.05). Mean arterial pressure remained unchanged during head up tilt at sea level, but it reduced from 82 mm Hg to 72 mm Hg (p < 0.05) during head-up tilt at high altitude. There were no altitude-related changes in the magnitude of the increase in forearm vascular resistance and the reduction in cardiac output and laser-Doppler skin blood flow in response to head-up tilt. The total peripheral resistance increased from 14.4 to 20.5 mm Hg.L-1 x min-1 (p < 0.05) during head-up tilt at sea level, but the change was not significant at high altitude. The lack of altitude-related changes in forearm vascular resistance and laser-Doppler skin blood flow during head-up tilt in the presence of attenuated total peripheral resistance response at high altitude may suggest that the orthostatic hypotension at high altitude is associated with a lower magnitude of vasoconstrictor response in the regions other than the limbs and the skin. PMID- 8447804 TI - Cardiovascular responses during recovery from exercise and thermal stress. AB - Although the central cardiovascular adjustments to exercise in the heat have been identified, little is known about the post-exercise hemodynamics during recovery from exercise and heat stress. This study examined heart rate (HR), stroke index (SI), cardiac index (CI), systemic vascular resistance (SVR), systolic (SBP) and diastolic (DBP) blood pressure in 8 males during 15 min of passive seated recovery preceded by 30 min of cycle ergometry (60% VO2max) on two separate occasions: under control (C) and heat stress (HS) conditions. During both recovery conditions, SI significantly declined (p < 0.05) to below pre-exercise values. No differences were observed between groups with respect to SI. The decrease in recovery HR was slower (p < 0.05) in HS than C. The greater elevation in HR during HS accounted for the relative increase in CI above that observed prior to exercise. The estimated SVR measured immediately following exercise in both groups was lower (p < 0.05) than pre-exercise values. By 5 min of C recovery, SVR returned to baseline values but remained significantly depressed (p < 0.05) for the entire HS condition. These results indicate that the pressor responses were attenuated during HS; however, CI was maintained above pre exercise levels due to higher HR responses compensating for the reduction in SI. Stimulation of the baroreceptor reflex and increased myocardial contractility could possibly explain the maintenance of output at a time when preload and afterload were reduced. PMID- 8447805 TI - Treatment efficacy of intramuscular promethazine for space motion sickness. AB - Intramuscular promethazine and its efficacy in the treatment of Space Motion Sickness (SMS) were evaluated using standardized questions administered during postflight debriefings to crewmembers immediately after their first Shuttle flight. Space Motion Sickness was graded as none, mild, moderate, or severe, based on published criteria. Immediate symptom relief (within 1-2 h) was evaluated by subjective reports; medication efficacy was based on scores derived from the four most frequently reported symptoms of SMS: nausea, vomiting, loss of appetite, and stomach awareness. Scores were given for each symptom, mild = 1, moderate = 2, and severe = 3, and added for a total score for each flight day. Following intramuscular (IM) promethazine on flight day 1, the scores were used to determine if the crewmembers were "sick" or "not sick" on flight day 2. On the basis of the scoring criteria, any subject with a score adding to greater than three, with any severe symptom, or with vomiting was defined as "sick." The comparison showed that 25% of crewmembers treated with IM promethazine were "sick" on flight day 2, compared to 50% of crewmembers who did not receive promethazine (p = 0.046). Of crewmembers treated with IM promethazine, 90% reported immediate symptom relief as well. Untreated crewmembers typically have slow symptom resolution over 72-96 h, and those treated with oral scopolamine/dextroamphetamine show delayed symptom development. This study suggests that intramuscular promethazine is an effective treatment for SMS and merits continued use and further controlled investigations. PMID- 8447806 TI - Retroperitoneal fibrosis as a cause of hypertension in an aviator: a case report. AB - The authors describe a case report of a previously healthy rotary-wing aviator who developed hypertension of unknown etiology. His 30 pack/year smoking history and hypercholesterolemia (ranging from 224-268) were significant. The initial evaluation revealed an elevated creatinine of 1.7 (normal to 1.5). Right-sided hydronephrosis was noted on ultrasound and the right kidney was poorly visualized on IVP. A subsequent retrograde cystoureterogram confirmed the hydronephrosis and demonstrated a distal calculus and stenosis, findings which were compatible with retroperitoneal fibrosis (RPF). This diagnosis was confirmed at surgery and the patient's ureters were freed. Following surgery, return of normal kidney function and satisfactory recovery, this aviator returned to full flying duty. A review of RPF is included. PMID- 8447807 TI - Pulmonary barotrauma after a free dive--a possible mechanism. AB - Pulmonary barotrauma during scuba diving is a life-threatening event. In a skin diver, who does not use compressed air, this complication is rare and its pathophysiology is not readily understood. We present a young, healthy skin diver who suffered pneumomediastinum and subcutaneous emphysema after a sequence of free dives to 5 m, and suggest a possible mechanism. PMID- 8447808 TI - Limitations to the study of man in space in the U.S. space program. AB - Research on humans conducted during spaceflight is fraught both with great opportunities and great obstacles. The purpose of this paper is to review some of the limitations to research in space in the United States with hope that an informed scientific community may lead to more rapid and efficient solution of these problems. Limitations arise because opportunities to study the same astronauts in well-controlled situations on repeated spaceflights are practically non-existent. Human research opportunities are further limited by the necessity of avoiding simultaneous mutually-interfering experiments. Environmental factors, including diet and other physiological perturbations concomitant with spaceflight, also complicate research design and interpretation. Technical limitations to research methods and opportunities further restrict the development of the knowledge base. Finally, Earth analogues of space travel all suffer from inadequacies. Though all of these obstacles will eventually be overcome, creativity, diligence, and persistence are required to further our knowledge of humans in space. PMID- 8447810 TI - Things may not be the way they seem. PMID- 8447809 TI - Rationale for a hyperbaric treatment capability at a Lunar Station. AB - Missions to establish a permanent presence on the Moon will include a significant amount of extravehicular activity (EVA), which carries the risk of decompression sickness (DCS). Factors which will influence that risk include: cabin and space suit pressure environments, frequency of an activity level during EVA, and the possibility of a loss-of-pressure mishap. These factors were considered for Space Station Freedom (SSF), resulting in the decision to include a hyperbaric airlock capable of treating DCS. Using concepts from operational medicine, the need for such a capability is determined by its influence on mission risk. In comparison to SSF, a Lunar Station will have gravity, a higher EVA rate, physically more DCS provocative EVA, and little, if any, capacity for medical evacuation. Therefore, unless Lunar mission planners can provide pressure environments that offer near zero risk of DCS for nominal operations, a hyperbaric treatment capability should be included. PMID- 8447811 TI - Aviators have been grounded due to the development of asthma. PMID- 8447812 TI - Effect of trans-cockpit authority gradient on Navy/Marine helicopter mishaps. PMID- 8447813 TI - The effects of wearing protective chemical warfare combat clothing on human performance. AB - U.S. Department of Defense studies to measure performance decrements associated with wearing chemical warfare (CW) protective combat clothing indicate that heat stress seriously degrades human performance. Even when heat stress is not a significant factor, performance of many combat, combat support, and combat service support tasks is degraded. In most field studies, many crews of combat units became operationally ineffective due to voluntary withdrawal of individual crewmembers. Many combined arms, field studies, and laboratory studies indicate that when CW-protective combat clothing is worn performance is seriously degraded for the detection of targets, engagement time, accuracy of fire, and manual dexterity tasks; and that a variety of psychological effects are created. Further, the degree of performance degradation varied with the tasks performed. Training in CW-protective combat clothing permits learning to modify procedures and consequently reduce negative effects, provided heat stress is not a significant factor. A growing body of evidence indicates there is inadequate training in the use of CW-protective combat clothing. A critical need exists for more and better training of skills needed under CW-conditions. PMID- 8447814 TI - Endothelins release 51Cr from cultured human cerebromicrovascular endothelium. AB - The effects of vasoactive peptides endothelins (ET-1, ET-2, ET-3, S6b, S6c) on release of 51Cr, production of inositol triphosphate (IP3), and release of arachidonic acid (AA) were examined in cultured microvascular endothelium derived from human brain (HBEC). ET-1 induced dose-dependent release of 51CR (EC50 = 7 +/ 2 nM), transient increase of IP3 (EC50 = 0.67 +/- 0.09 nM), and sustained release of AA (EC50= 59 +/- 7 nM) from HBEC. Under the same experimental conditions, viability of the cells was preserved (> 97%) as assessed by exclusion of vital dye trypan blue and release of lactate dehydrogenase (LDH). Dexamethasone (1 microM) inhibited ET-1-induced AA release, whereas it was ineffective on 51Cr release. Protein kinase C (PKC) inhibitor H7 (200 nM), calcium channel blocker verapamil (10 microM), or IP3 receptor antagonist ryonidine (5 microM) reduced ET-1 (100 nM)-induced release of 51Cr. These findings indicate that endothelins can induce an increase of HBEC permeability by a receptor-specific activation of PKC and intracellular calcium mobilization. PMID- 8447815 TI - Cholesterol enrichment of arterial smooth muscle cells upregulates cytokine induced nitric oxide synthesis. AB - Endothelium-derived relaxing factor/nitric oxide (EDRF/NO) is produced by the vascular wall and is a key modulator of vascular tone and blood pressure. NO is also produced by vascular smooth muscle (VSMC) where it can inhibit proliferation. Since cytokine-activated VSMC proliferation is a major event in the development of atherosclerosis, we investigated the influence of cholesterol (CE)-enrichment of VSMC on cytokine-induced NO synthesis. Treatment of VSMC with native LDL for one week did not promote CE-accretion or alter NO production following exposure to endotoxin (LPS). In contrast, CE-enrichment by cationized LDL augmented LPS-induction of NO synthesis 2-5-fold. While TNF-alpha promoted little NO synthesis in control VSMC, it was very potent after CE-enrichment. Similarly, CE-enrichment augmented IL-1 alpha-induced NO synthesis. However, CE enrichment did not affect the synergistic induction of NO synthesis by cytokines in combination with IFN-gamma. Our findings suggest that CE-enrichment of VSMC upregulates signal transduction pathways which mediate cytokine and LPS induction of NO synthase activity. PMID- 8447816 TI - Histidine residues are essential for the surface binding and autoactivation of human coagulation factor XII. AB - The role of histidine residue in the surface binding and autoactivation of human factor XII has been investigated by chemical modification with diethyl pyrocarbonate. It is found that low concentrations of diethyl pyrocarbonate have profound inhibitory effects on the surface binding activity of factor XII. At 2.5 fold molar excess of the reagent, six histidines are modified and 80% of the amidolytic activity is lost. Electrophoretic studies show that the modified protein has lost the capacity to bind to the surface, resulting in diminished proteolytic autoactivation. When modification is performed in the presence of the surface, dextran sulfate, two of the six histidines are protected from modification and the amidolytic activity is completely preserved. It is concluded that histidine residues in factor XII play key role in its surface binding activity. PMID- 8447817 TI - Mouse P19 embryonal carcinoma cells express functional histamine H1-receptors. AB - In the present study, we have investigated the response in P19 embryonal carcinoma (EC) cells to histamine. We show that these cells, that resemble the pluripotent cells of an early mouse embryo, respond to histamine addition by a transient increase in intracellular Ca2+. The response is stereoselectively inhibited by the enantiomers of the H1-receptor antagonists chlorpheniramine and cicletanine. [3H]-mepyramine was found to bind with high affinity (Kd 4 nM) to a membrane preparation of P19 EC cells. The profile of these binding sites corresponded well with the results of the Ca2+ measurements. A high affinity [3H] mepyramine binding site was also identified on intact cells. These data demonstrate that embryonal carcinoma cells express functional histamine H1 receptors and suggest that histamine might act as a regulatory factor in the early development of the mouse embryo. PMID- 8447818 TI - In vitro phosphorylation of mouse osteopontin expressed in E. coli. AB - To understand the role of post-translational modifications on the structure and function of osteopontin, a secreted glycosylated phosphoprotein, we expressed mouse osteopontin in E. coli as a fusion protein with glutathione-S-transferase (GST). The purified fusion protein was cleaved by factor Xa generating GST (26 kDa) and recombinant osteopontin (60 kDa). The fusion protein was phosphorylated in vitro by cytosolic, microsomal, and casein kinase II fractions from mouse kidney homogenates. The fusion protein and recombinant osteopontin were also phosphorylated by the catalytic subunit of cAMP-dependent protein kinase. The suitability of the fusion and recombinant proteins as model substrates for the study of the function(s) and post-translational modifications of osteopontin is discussed. PMID- 8447819 TI - Phosphatidic acid directly activates endothelial cell protein kinase C. AB - The metabolism of phosphatidic acid (PA) yields diacylglycerol (DAG), a known activator of protein kinase C (PKC). To examine potential direct effects of PA on PKC activation, PKC purified from bovine pulmonary artery endothelial cells (BPAEC) was utilized in an in vitro assay examining gamma-[32P]ATP phosphorylation of H1 histone. In the presence of Ca2+ and phosphatidylserine (PS), DAG (80 microM) produced maximal PKC activity (6.4 pmol gamma-[32P]ATP incorporated/microgram/min). Dioleoyl-PA (80 microM) and 1-stearoyl,2-arachidonyl PA (80 microM) activated PKC in a concentration-dependent manner (maximal activity of 2.01 +/- 0.1 pmol/microgram/min). Unlike unlabelled phorbol esters or DAG, dioleoyl-PA did not significantly alter the binding of [3H]-phorbol dibutyrate to PKC, suggesting that PA directly activates endothelial cell PKC in a manner distinct from DAG-mediated PKC activation. PMID- 8447820 TI - Band 4.1 enhances spectrin binding to phosphatidylserine vesicles. AB - Erythroid band 4.1 enhances the binding of erythroid spectrin to phosphatidylserine vesicles under conditions of ionic strength and at protein concentrations similar to those in the red cell. The extent of enhancement depends on the concentration of band 4.1; at 2 microM 4.1, spectrin binding increases approximately 10-fold (to 600 mumoles/mole lipid). The Kd is 0.5 microM, as measured by SDS-PAGE of protein-bound vesicles recovered by ficoll gradient centrifugation. The 4.1-enhanced binding of spectrin was also measured by a gel filtration assay. The electrostatic nature of the enhancement of spectrin binding is indicated by its dependence on the phosphatidylserine content of the vesicles. PMID- 8447821 TI - RNA-binding patterns in total human tissue proteins: analysis by northwestern blotting. AB - We have developed a reproducible Northwestern (NW) blotting method to identify general patterns of RNA-binding proteins in total human tissue homogenates and have identified some of the factors contributing to this reproducibility. Unfractionated homogenates of human brain tissue were separated by SDS-PAGE, electrotransferred wet to nitrocellulose, and probed with in-vitro-transcribed labeled RNAs. Approximately ten size classes of RNA-binding proteins were observed consistently and reproducibly. Although sequence-independent electrostatic RNA-protein interactions likely contributed to most of the binding, binding to some proteins was shown to be more dependent on protein conformation: binding was not blocked by preincubation with single- or double-stranded DNA, nor with poly(A) RNA, but preincubation with tRNA revealed a distinct subset of RNA binding proteins. In addition, preincubation with RNA, but not DNA, revealed a previously undetected RNA-binding protein of approximately 90 kDa. The NW blotting method described here can be used to reveal tissue-specific differences in RNA-binding patterns. PMID- 8447822 TI - Immunological identification of the Shaker-related Kv1.3 potassium channel protein in T and B lymphocytes, and detection of related proteins in files and yeast. AB - Shaker-related potassium (K+) channel proteins contain sequences which exhibit remarkable conservation across species. We have generated polyclonal anti-peptide antibodies (Abs) which cross-react with peptide epitopes of several Shaker related channels (Kv1.1, 1.2 and 1.3), in addition to a Kv1.3-specific Ab. The Kv1.3-specific Abs react with a protein expressed in human T-cells (Jurkat and PBLs), as well as in mouse T-cells (EL-4) and pre-B cells (230.37). The cross reactive Abs detect the Shaker protein in Drosophila melanogaster, in addition to an immunologically related protein in the yeast Saccharomyces cerevisiae. Abs which recognize these shared epitopes could serve for the identification and biochemical characterization of Shaker-related proteins in diverse organisms. PMID- 8447823 TI - Sequence characterization of a novel alpha-neurotoxin from the king cobra (Ophiophagus hannah) venom. AB - Several postsynaptic neurotoxins (alpha-neurotoxins) with distinct pharmacological and biochemical properties were isolated and purified from the King cobra venom (Ophiophagus hannah) by employing sequentially preparative-scale cation-exchange chromatography on SP-Sephadex C-25 coupled with gel filtration and reversed-phase HPLC. The complete sequence of one neurotoxin was determined by N-terminal Edman degradation with the automatic pulsed-liquid phase sequencer on some peptide fragments generated from the endopeptidases, i.e. trypsin, S. aureus V8 protease and lysyl endopeptidase. This novel neurotoxin is a basic polypeptide of pI 9.05, consisting of 72 amino-acid residues with 10 cysteine residues. It is found to share about 60% sequence homology with Toxins a and b isolated from the same venom and the well established alpha-bungarotoxin, a major postsynaptic toxic ligand for acetylcholine receptor isolated from Bungarus multicinctus. The characterized alpha-neurotoxin molecules were also shown to bind specifically with nicotinic acetylcholine receptors of the electric eel, Torpedo californica. PMID- 8447824 TI - Testins are structurally related to the mouse cysteine proteinase precursor but devoid of any protease/anti-protease activity. AB - Testin I (M(r) 35,000) and testin II (M(r) 37,000) (testins) are two structurally and immunologically related testicular proteins that are actively synthesized and secreted by Sertoli cells. Treatment of adult rats with busulfan to destroy germ cells selectively in the testis could lead to a significant increase in the testicular testins level; as the germ cells reappeared in the testis, the testicular testins level declined and returned to the normal level. These observations indicated that the testicular content of testins in the rat is inversely correlated to the number of germ cells. When the partial N-terminal amino acid sequences for testin I and testin II were compared with the existing protein data base at Protein Identification Resource, it was noted that they displayed remarkable identity with CTLA-2 alpha and CTLA-2 beta, two novel molecules expressed in mouse activated T lymphocytes and mast cells, and the mouse cysteine proteinase proregion. When purified testins were assayed for the proteolytic and anti-protease activity using [14C]-casein, it was noted that it possessed neither proteolytic nor anti-protease activity, suggesting that it is not functioning as a protease and/or protease inhibitor in the testis. PMID- 8447825 TI - Comparative analysis of human and Dutch-type Alzheimer beta-amyloid peptides by infrared spectroscopy and circular dichroism. AB - The 42 amino acid beta A4 peptide is the major constituent of the senile plaques, one of the hallmark neuropathological lesions of Alzheimer's disease. While C terminally truncated variants were shown to be present in normal body fluids, a single Glu-->Gln change in the 39 amino acid form of beta A4 results in accelerated fibril formation in the brains of patients with Dutch-type hereditary cerebral hemorrhage with amyloidosis. In this study we used Fourier-transform infrared and circular dichroism spectroscopies on synthetic peptides to demonstrate that this mutation results in altered secondary structure in membrane mimicking solvents, characterized by a considerably higher beta-structure content for the mutant peptide. Moreover, extreme high and low pH were less effective in eliminating the beta-conformation for the Dutch-variant than for the normal human sequence. PMID- 8447826 TI - A new protein kinase C, nPKC eta', and nPKC theta are expressed in human platelets: involvement of nPKC eta' and nPKC theta in signal transduction stimulated by PAF. AB - We have detected in human platelets two protein kinase C isozymes that have not been reported previously. Using an anti-nPKC theta antibody and Western blotting, we calculated the molecular weight of platelet nPKC theta as 79K. This molecular weight is identical to that described for nPKC theta in skeletal muscle and in COS cells transfected with the nPKC theta-cDNA. Using an anti-nPKC eta antibody, we determined the molecular weight of an immunoreactive protein, which we called nPKC eta', to be 95K. This molecular weight is higher than that of nPKC eta found in lung and skin tissue of 82K and 78K, and it is higher than nPKC eta of COS cells transfected with the nPKC eta-cDNA expression plasmid. Together with previous reports, these findings make the total number of PKC isozymes in human platelets equal to six. These are the PKC isozymes: alpha, beta, delta and zeta, which have been previously described, and eta' and theta which we describe here. To assess the functionality of these new PKC isoforms, we stimulated platelets with PAF. We found a 200% and 175% increase in the levels of membrane-bound nPKC eta' and nPKC theta, respectively, in human platelets stimulated by PAF. A concomitant decrease in the level of these isoforms in the cytoplasm was observed. This PAF-induced translocation was time-dependent, and it reached its peak after a 1 minute incubation of human platelets with PAF for nPKC theta and 30 seconds for nPKC eta'. PMID- 8447827 TI - Detection of Mg(2+)-dependent endonuclease activity in myeloid leukemia cell nuclei capable of producing internucleosomal DNA cleavage. AB - We detected Mg(2+)-dependent, Ca(2+)-independent endonuclease activity in non apoptotic myeloid leukemia cell nuclei using autodigestion method which cleaved the chromatin of the autologous leukemia cells to an oligonucleosomal length pattern. Similar endonuclease activity could be successfully recovered in the protein extracts of the human leukemia cell nuclei. The extracts consistently elicited characteristic DNA cleavage of another leukemia cell (KG-1) nuclei as the target, the enzyme activity of which had been inactivated. We propose that this method is a useful tool for the study of endonucleases involved in apoptosis. PMID- 8447828 TI - Characterization of the replicon from plasmid pAC1 from Acetobacter pasteurianus. AB - A panel of recombinant plasmids pACK5 and pACT7 was prepared by introducing kanamycin and tetracycline resistance into the partially split plasmid pAC1 which contained replicon isolated from Acetobacter pasteurianus. The replicon in plasmid pAC1 is compatible with the ColE1 replicon. Compared to pBR322, the plasmid had more than 30 copies per chromosome in Escherichia coli cells. Plasmids were transformed into E. coli DH1, Acetobacter pasteurianus 3614, Acetobacter aceti 3620, Shigella, Citrobacter, and Brevibacterium flavum cells, and the stability of plasmid DNA was tested after cultivation in nonselective conditions. PMID- 8447829 TI - Alpha,N-acetyl beta-endorphin [1-8] is the terminal product of processing of endorphins in the melanotrope cells of Xenopus laevis, as demonstrated by FAB tandem mass spectrometry. AB - The major N-terminal acetylated endorphin of the pars intermedia of Xenopus laevis was purified and submitted to fast-atom bombardment tandem mass spectroscopy. The collisionally induced dissociation MS/MS spectrum of the [M+H]+ ion revealed sufficient fragment ions to determine unambiguously the identity of the peptide as alpha,N-acetyl beta-endorphin [1-8], the sequence of which was predicted on the basis of the nucleotide sequence of Xenopus POMC cDNA. The determination was confirmed by showing that the synthetic peptide of this structure had identical FAB tandem mass spectrometric characteristics as the endogenous endorphin. We conclude that alpha,N-acetyl beta-endorphin [1-8] is the terminal product of processing of endorphins in the melanotrope cell of Xenopus laevis. PMID- 8447830 TI - Secretion of a neuropeptide-metabolizing enzyme similar to endopeptidase 22.19 by glioma C6 cells. AB - An endopeptidase capable of metabolizing a number of neuropeptides and generating [Met5] and [Leu5] enkephalin from enkephalin-containing peptides is secreted by glioma C6 cells. This neutral endopeptidase that is likely to be a thiol protease, has a Mr of 71KDa and is effective only towards oligopeptides. Its specificity towards neuropeptides is identical to that of soluble endopeptidase 22.19. Moreover, when a partially purified preparation of enkephalin-generating enzyme secreted by glioma C6 cells was submitted to immunoblotting, an antiserum against purified brain endopeptidase 22.19 recognized a single band at Mr of 71 KDa. These data suggest that the soluble endopeptidase 22.19 may be secreted by glioma C6 cells thus allowing its participation in the biotransformation of opioid peptides in the CNS. PMID- 8447831 TI - Cyclooxygenase-derived metabolites of 8,9-epoxyeicosatrienoic acid are potent mitogens for cultured rat glomerular mesangial cells. AB - The mitogenic effects of 11(R)-hydroxy-8,9-epoxyeicosatrienoic acid (EET) enantiomers were investigated in cultured rat glomerular mesangial cells. Both 11(R)-hydroxylated 8(R),9(S)- and 8(S),9(R)-EET at 1 microM stimulated [3H] thymidine incorporation to 300% and 280%, with 50% maximal effect occurring at 8 x 10(-9) M and 1 x 10(-8) M, respectively. Similar concentration-dependent effects were observed in stimulating induction of the immediate early gene, c fos. Mitogenic activity of the 11(R)-hydroxylated enantiomers was not affected by prior downregulation of protein kinase C, suggesting involvement of protein kinase C-independent mechanisms. These findings suggest that either trans- or intracellular metabolism of 8,9-EET by cyclooxygenase occurs during inflammatory glomerular diseases and that the resulting metabolites are involved in mesangial cell proliferation. PMID- 8447832 TI - Molecular mechanisms of the increased glucose transport in transformed FRTL-5 rat thyroid cells. AB - We investigated the molecular mechanisms involved in the glucose carrier (Glut 1) regulation in FRTL-5 cells and two derived transformed clones (SRC and Ki-Mol cells). When compared to the wild-type strain, SRC and Ki-Mol cells showed an increase in both glucose consumption and uptake (about 60 fold), associated with 6-8 fold higher Glut 1 mRNA levels. Transcriptional studies revealed a 2- to 3 fold increased activation of the gene in the transformed cells, suggesting that transcription alone cannot fully account for the higher Glut 1 gene expression. Western blot studies showed an increase of the Glut 1 protein in SRC and Ki-Mol cells, associated with a different gel migration pattern and a disparate distribution rate between the plasma membrane and the microsomal fraction. These data indicate that the higher rate of glucose uptake observed in SRC and Ki-Mol cells is associated to an increase in Glut 1 gene expression, and that also changes in the subcellular distribution and probably in the structure of Glut 1 protein are present. PMID- 8447833 TI - cDNA expression studies of rat liver aryl sulphotransferase. AB - A cDNA encoding an isoenzyme of rat liver aryl sulphotransferase was isolated from a rat liver bacteriophage Lambda gt 11 library by the polymerase chain reaction technique. The resulting cDNA was functionally expressed in COS-7 cells and characterised by determining the sulphating capacity of the cells with a range of substrates. The COS-expressed enzyme catalysed the sulphation of both phenol and dopamine with Kms of the same order as those obtained for the high affinity isozyme in rat liver cytosol, while low activity was observed with tyrosine methyl ester. The common food additive vanillin was also a good substrate for sulphate conjugation. The sulphation of vanillin catalysed by the COS-expressed enzyme was consistent with a single enzyme system, in contrast, the kinetics of the reaction catalysed by cytosolic sulphotransferase indicated that vanillin was sulphated by more than one isozyme. PMID- 8447834 TI - Nucleotide sequence of the luxC gene encoding fatty acid reductase of the lux operon from Photobacterium leiognathi. AB - The nucleotide sequence of the luxC gene (EMBL Accession No. 65156) encoding fatty acid reductase (FAR) of the lux operon from Photobacterium leiognathi PL741 was determined and the encoded amino acid sequence deduced. The fatty acid reductase is a component of the fatty acid reductase complex. The complex is responsible for converting fatty acid to aldehyde which serves as the substrate in the luciferase-catalyzed bioluminescent reaction. The protein comprises 478 amino acid residues and has a calculated M(r) of 53,858. Alignment and comparison of the fatty acid reductase of P. leiognathi with that of Vibrio harveyi B392 and Vibrio fischeri ATCC 7744 shows that there is 70% and 59% amino acid residues identity, respectively. PMID- 8447835 TI - Human anti-endoplasmic reticulum autoantibodies produced in aromatic anticonvulsant hypersensitivity reactions recognise rodent CYP3A proteins and a similarly regulated human P450 enzyme(s) AB - Hypersensitivity reactions to aromatic anticonvulsants are associated with anti liver microsomal antibodies which recognise rodent proteins. The reactivity of these antibodies, the regulation of the rodent antigens and the identity of the human autoantigen have been investigated. Dexamethasone elevated markedly the levels of an immunoreactive mouse protein(s) which exhibited a Mr (53 kDa) and inducibility consistent with the major Cyp3a product. Immunoblots conducted with hepatic microsomes from control and induced rats and purified rat P450s confirmed that these antibodies also recognised constitutive (3A2) and inducible (3A1) rat CYP3A products. Negligible reactivity was observed with microsomes from human B lymphoblastoid cell lines expressing CYP1A1, 1A2, 2A6, 2D6, 2E1, 3A4 or epoxide hydrolase. Analysis of a phenotyped human liver bank revealed that the antibodies recognised a 52.5 kDa microsomal protein which exhibited marked heterogeneity in its expression and appeared to be regulated co-ordinately with human CYP2C8 and 3A3/4. The inter-individual variation in the expression of this protein(s) and its potential induction by anticonvulsant therapy together with an inherited deficiency in drug detoxification capacity may explain predisposition to these immunoallergic reactions. PMID- 8447837 TI - A continuous spectrophotometric direct assay for peptidyl prolyl cis-trans isomerases. AB - m-Nitrotyrosine incorporated into proline peptides of the general sequence -Xxx Pro-Tyr(m-NO2)- responds to cis-trans Xxx-Pro conformational transition by changes in the pKa of its side-chain hydroxyl (Garel and Siffert, 1979). We exploited this effect to develop a continuous direct (uncoupled) assay for peptidyl prolyl cis-trans isomerases. Prior to the enzyme assay, the cis-trans equilibrium is perturbed in favor of the cis isomer by dissolving the substrate H Ala-Ala-Pro-Tyr(m-NO2)-Ala-NH2 in a 470 mM solution of LiCl in trifluoroethanol. Upon addition of substrate to the biological buffer, the conformational equilibrium characteristic for the aqueous medium is restored, and the Ala-Pro isomerization is monitored spectrophotometrically. PMID- 8447836 TI - Expression of fatty acid-binding proteins in the developing mouse mammary gland. AB - Proteins of 14,000 daltons (SLP-14) were isolated and partially characterized from mouse mammary glands of different developmental stages. The purified proteins were partially sequenced at the amino acid level. The SLP-14 belong to the family of fatty acid-binding (FABP) proteins. The major SLP-14 expressed was a reflection of the differentiation stage of the mammary gland. Within the regions sequenced for each protein, virgin mouse mammary gland (primarily adipocytes) expressed a protein 100% homologous to adipocyte lipid binding protein whereas pregnant and lactating mouse mammary glands expressed a protein highly homologous to mouse heart fatty acid binding protein. In the lactating gland, the isolated protein was 97% identical to the heart FABP over a 98 amino acid stretch. We could not detect the 14Kd protein identified as mammary gland growth inhibitor (MDGI) which is also a member of the FABP family and highly homologous to heart FABP. A rabbit antiserum to the rat mammary SLP-14 recognized the SLP-14 proteins in mouse and rat mammary gland, skeletal muscle and heart, whereas it failed to recognize the SLP-14 in liver, intestine and other organs. These data indicate that the SLP-14 detected in rodent mammary gland is of the fatty acid-binding protein family. On the basis of amino acid sequence, the major form in the differentiated mouse mammary gland is apparently FABP and not MDGI. MDGI may be a protein in low abundance and/or localized to a specific group of mammary epithelial cells. PMID- 8447838 TI - A provisional mechanism for regulating the aminoacyl-tRNA synthetases. AB - A mechanism is outlined for regulating aminoacyl-tRNA synthetases with a nonheme iron-containing protein serving as the key regulator. This mechanism is formulated from experiments with a complex-bound valyl-tRNA synthetase from yeast that is activated by thiols, by tRNA, and by an iron-containing protein preparation with characteristic spectral properties. PMID- 8447839 TI - Uptake and effects of thiopental in isolated heart preparations of the rat in the presence of halothane. AB - The uptake of thiopental (CAS 76-75-5) (0.13-0.27 mmol.l-1) into tissue of rat hearts (Langendorff's preparation) was studied in the presence of halothane (CAS 151-67-7). Up to a thiopental concentration of 0.19 mmol.l-1 in the perfusion medium its concentration in heart tissue was significantly increased vs. control when halothane (0.8 vol%) simultaneously was present; using 0.13 mmol.l-1 thiopental and 0.8, 1.5 or 2.0 vol% halothane this increase amounted +12%, +29% and +43%, respectively. Frequency of spontaneously beating rat hearts decreased in the presence of increasing thiopental concentrations. 0.8 vol% halothane (without thiopental) did not influence heart rate; in the presence of thiopental it attenuated heart rate reduction. This attenuation was absent in hearts of rats pretreated with reserpine. 1.5 vol% halothane (itself also without influence on heart rate) increased the negative chronotropic action of thiopental. In isolated right and left atria of rat hearts frequency and contractility decreased concentration-dependently in the presence of thiopental; simultaneously present halothane additionally increased this negative chronotropic and negative inotropic effect of thiopental. PMID- 8447840 TI - Antidepressive effects of the stereoisomer cis-dosulepin hydrochloride. AB - The central action of cis-dosulepin (CAS 113-53-1) was compared with that of its antidepressant stereoisomer trans-dosulepin, cis-dosulepin exerted weaker anti reserpine, anti-tetrabenazine, and 3H-5-HT (serotonin) uptake inhibiting actions than trans-dosulepin, but cis-dosulepin's inhibition of 3H-dopamine and 3H norepinephrine uptake was slightly more potent than that of trans-dosulepin. On the other hand, cis-dosulepin exhibited extremely potent anticholinergic action in oxotremorine induced tremor, isolated ileums and the 3H-quinuclidinyl benzilate binding test. It also showed potent apomorphine enhancing action and shortened the period of immobility in the forced swimming test in animals. The pharmacological profile of cis-dosulepin appears interesting with respect to investigating the mechanism of action of antidepressants. PMID- 8447841 TI - Radioimmunological analysis of ethinylestradiol in human serum. Validation of the method and comparison with a gas chromatographic/mass spectrometric assay. AB - The majority of combination oral contraceptives contain ethinylestradiol (EE2, CAS 57-63-6) as estrogenic component at doses between 50 and 20 micrograms/unit. Since the concentrations of EE2 in the serum of women under oral contraceptive (OC) therapy are in the lower pg-range, highly sensitive and specific analytical methods are required. Radioimmunoassay (RIA) has been the method of choice, but evidence of specificity in the presence of the coadministered progestogens and their metabolites has not always been provided. The present study compares two radioimmunological methods, which use the same antiserum but different sample volumes and standard curves (extracted vs. non-extracted), with a newly developed gas chromatographic/mass spectrometric (GC/MS) method, in order to cross-validate the methods. For that purpose, 51 serum samples obtained from women who had been taking two different combination oral contraceptives were analysed independently by all three methods. The specificity of the antiserum was further examined by submitting ex vivo serum samples obtained from OC-users to a combination of high pressure liquid chromatography (HPLC) and RIA. The results obtained by the three methods were very similar and correlation coefficients (r) obtained from linear regression analysis were about 0.7. There was no interference from the coadministered progestins on the analysis of EE2 as carried out by the three methods. There were no metabolites in the extracts of ex vivo serum samples which showed cross-reactivity with the antiserum used. Modifications of the radioimmunoassay procedure did not markedly affect the results of EE2 determination. If properly validated, radioimmunoassay can be used as an alternative to GC/MS in pharmacokinetic studies. PMID- 8447842 TI - [Bioavailability of folic acid following intramuscular and intravenous administration to healthy volunteers]. AB - Bioavailability of Folic Acid Following Intramuscular and Intravenous Administration to Healthy Volunteers 2 mg folic acid (Folsan 2, CAS 59-30-3) were either i.m. or i.v. administered as injection solution to 15 male healthy subjects within an open balanced two-way crossover study. The concentration-time profile of folic acid was determined up to 12 h p.a. in serum and urine using a radioassay. Each change-over phase included a 9 days lasting saturation phase with once-per-day oral administration of a tablet containing 5 mg folic acid. Saturation was performed in order to guarantee filled-up endogenous folate storage compartments in the body of the subjects. After a four-day wash-out phase the subjects were confined and the basic serum level and basic renal 0-12 h folate excretion determined. On the following morning the respective dose of 2 mg folic acid was either i.m. or i.v. applied to the subjects (treatment day 14). 11 (i.m.) and 15 (i.v.) venous blood specimens were drawn up to 12 h p.a. and urine collected following the same schedule as the day before in 4 different fractions. The mean predose level of folic acid in serum was 13.2 +/- 4.85 ng/ml before the i.m. administration and 13.3 +/- 5.59 ng/ml before i.v. administration. The serum concentration data following the respective single administrations were corrected by subtraction of the individual predose values. After 0.50 +/- 0.19 h (mean tmax) the folate serum level increased by 101 +/- 27.2 ng/ml after the i.m. dose. Serum concentration decreased in the following 6-8 h approximately to the predose values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447843 TI - New basic esters of 2-phenyl-3-methyl-4-oxo-4H-1-benzopyran-8-carboxylic acid endowed with spasmolytic properties. Synthesis and pharmacological pharmacokinetic evaluation. AB - In order to obtain new analogs of flavoxate endowed with higher stability and possibly higher potency, a new series of basic esters of 2-phenyl-3-methyl-4-oxo 4H-1-benzopyran-8-carboxylic acid (MFCA) has been prepared and investigated. Derivatives in which the structure of flavoxate was modified by branching and lengthening of the estereal alkyl chain were synthesized, together with the conformationally restricted N-piperidinyl derivatives. Esters containing in their structure various alicyclic tertiary amines which are present in natural or synthetic drugs endowed with spasmolytic properties, mainly of anticholinergic nature, were also prepared. The stability in aqueous solution, acute toxicity in mouse, and in vitro spasmolytic properties of the new compounds were investigated in comparison with flavoxate. Based on the results obtained from this screening procedure, 3 compounds were selected for further investigation. In this phase, further pharmacological and stability testing as well as preliminary animal pharmacokinetic investigations were carried out. The obtained results suggested the choice of 1,1-dimethyl-2-(1-piperidinyl)ethyl 2-phenyl-3-methyl-4-oxo-4H-1 benzopyran-8-carboxylate HCl (Rec 151 2053, terflavoxate, CAS 86433-39-8) as a candidate for preclinical development. The deeper pharmacological characterization of this compound, carried out mainly in comparison with flavoxate, terodiline, and oxybutynin confirmed its good spasmolytic activity. PMID- 8447844 TI - Inhibitory effect of intraduodenal infusion of loxiglumide on pancreatic exocrine secretion. AB - Inhibitory effect of loxiglumide (D,L-4-(3, 4-dichlorobenzoylamino)-5-(N-3 methoxypropyl-pentylamino)-5- oxo-pentanoic acid, CAS 107097-80-3) on exocrine pancreatic secretion was compared between intraduodenal and intravenous administration. Doubling doses of intravenous cholecystokinin octapeptide (CCK-8) resulted in a dose-dependent increase of pancreatic secretion from 50 to 400 ng/kg/h. Both intraduodenal and intravenous loxiglumide of 5 and 10 mg/kg/h produced a dose-dependent inhibition of the pancreatic protein secretion to all doses of CCK-8. Cumulative increment of pancreatic protein output was inhibited by 79% and 77% at 10 mg/kg/h of intraduodenal and intravenous loxiglumide, respectively. Extents of the inhibition were similar to each other between the two routes of loxiglumide infusion. However, plasma levels of loxiglumide after intraduodenal administration were about half of those observed after intravenous administration of the corresponding dose, although plasma CCK levels were not different. Intraduodenal loxiglumide is as effective as intravenous loxiglumide in inhibitory potency on pancreatic secretion. Therefore, possible therapeutic indications of oral loxiglumide could be expected. PMID- 8447845 TI - Pharmacokinetics of beclobric acid enantiomers and their conjugates after single and multiple oral dosage of racemic beclobrate. AB - The chiral lipid regulating agent beclobrate (CAS 55937-99-0), which was marketed as racemate, is - like clofibrate - rapidly hydrolyzed to beclobric acid immediately after absorption. Pharmacokinetic data were only available for the total concentration, but not for the two enantiomers. Therefore, the pharmacokinetics of (-)- and (+)-beclobric acid were studied in 8 healthy male volunteers after a single 100 mg dose of rac-beclobrate and under steady state conditions, i.e. after repetitive dosage of 100 mg beclobrate once daily for 8 days. After oral administration unchanged beclobrate was not detected in plasma. Distinct differences were found in the pharmacokinetic parameters of the two beclobric acid enantiomers. The maximum plasma concentrations and the AUC values of the (+)-enantiomer exceeded those of the (-)-enantiomer nearly 2 fold. Beclobric acid, the active metabolite, is converted to an acyl glucuronide. The diastereomeric glucuronides were detected in the plasma of all volunteers, but the differences in the pharmacokinetics were not as evident as for beclobric acid enantiomers. A comparison of the measured steady-state beclobric acid enantiomer concentration and those simulated on the basis of the parameters (open two compartment model) obtained for a single beclobrate dose showed that the accumulation factor is slightly but nevertheless significantly higher than predicted. PMID- 8447846 TI - Synthesis and anti-inflammatory properties of benzoyl, halogenobenzoyl or cinnamoyl substituted 1-benzoxepanes and 2-methyl-1-benzoxolanes. AB - A series of new 7-acyl substituted 1-benzoxepanes and 5-acyl substituted 2-methyl 1-benzoxolanes were synthesized and studied for anti-inflammatory properties. The benzoyl derivatives were more active than the corresponding halogenobenzoyl derivatives and previously reported structural analogues containing less methylene groups in their heterocyclic ring. The introduction of a methyl group at the 2-position of 5-cinnamoyl-1-benzoxolane heterocyclic ring significantly potentiated the activity. Anti-inflammatory and analgesic effects of 7-benzoyl-1 benzoxepane and 5-cinnamoyl-2-methyl-I-benzoxolane were less pronounced than those of indomethacin and diclofenac but greater than those of acetylsalicylic acid (ASA). Both compounds were less toxic and 5-cinnamoyl-2-methyl-1-benzoxolane was also less gastrotoxic than all the reference drugs mentioned above. Therapeutic indices of 5-cinnamoyl-2-methyl-1-benzoxolane were greater than those of diclofenac and significantly greater than those of ASA and indomethacin. PMID- 8447847 TI - In vivo and in vitro stereoselective metabolism of mianserin in mice. AB - The preparative separation of mianserin (CAS 24219-97-4) enantiomers, both of unlabelled compound in g-amounts and radiolabelled compound as used for metabolism studies in microgram-amounts, is facilitated by means of LC on microcrystalline cellulose triacetate (CTA). HPLC on CTA is used for confirmation of the enantiomeric purity. After administration of 14C-labelled enantiomers to mice AUC and Cmax of the S-enantiomer were increased by 48% and 128%, resp. With regard to urinary metabolites from rac mianserin 97.9% of the radioactivity was excreted in conjugated form. Glucuronidation (82.1%) was preferred to sulphation (15.8%). The excretion of N-demethylated metabolites was increased after dosage of R-mianserin, demonstrated by an R:S ratio of 5.2 (8-hydroxy-demethylmianserin glucuronide), while the S-enantiomer was mainly metabolized to 8-hydroxymianserin glucuronide (S:R = 3.2). The 8-hydroxymianserin N(2) oxide was selective for the S-isomer. In mouse liver homogenate with NADPH as cosubstrate the overall extent of metabolism was greater for R-mianserin (87.1% R vs. 44.1% S). The R-enantiomer prefers N-demethylation (R:S = 3.4-4.0) while more N-oxidized metabolites are formed from S-mianserin (S:R = 2.5), which is in agreement with published data on human liver microsomes. The reported stereoselectivities were confirmed in liver homogenates of both male and female mice, whereas the extent of N-demethylation and N-oxidation was dependent on the gender. The in vitro data suggest that hepatic metabolism of mianserin is stereoselective. N-demethylation and N oxidation demonstrate opposite stereoselectivities, which is also reflected in the urinary metabolic pattern of the enantiomers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447848 TI - Pharmacokinetic study of fentiazac and its main metabolite hydroxyfentiazac in the elderly. AB - The pharmacokinetics of fentiazac (F, CAS 18046-21-4) and hydroxyfentiazac (OH-F) were estimated in 12 elderly (> 76 years). After an oral single dose of 200 mg F, the plasma and urine profiles were determined using high-performance liquid chromatography with a fluorescence detection. When compared to results obtained in young adults, the maximum plasma concentrations (5.4 +/- 1.9 mg/l) and-the time to reach them were identical. The terminal half-life (7.0 +/- 9.1 h) was longer, due to a slight increase of the apparent volume of distribution and a decrease of the elimination clearance. The findings suggest that the dosage regimen of this drug should be decreased in the elderly. Moreover, the variability of the pharmacokinetics being larger, individual adaptation of the daily dose should be performed. PMID- 8447849 TI - Erythromycin and 2'-acetyl erythromycin concentrations in plasma and pelvic tissues after repeated doses of erythromycin acistrate. AB - The concentrations of erythromycin (E) and 2'-acetyl erythromycin (2'-AE) in female pelvic organs, i.e. endometrium, myometrium, ovary and Fallopian tube, as well as in plasma, were determined after oral dosing of erythromycin acistrate (EA, CAS 96128-89-1), a erythromycin prodrug. Ten patients undergoing selective gynecological operation were given three doses of EA (400 mg) at 8-h intervals immediately before the operation. Tissue samples were taken 75-205 min after the intake of the last dose. Blood samples were collected immediately prior to and up to 8 h after the intake of the last dose. High total antibiotic (erythromycin + 2'-acetyl erythromycin) concentration in plasma were measured throughout the dose interval after the last dose. The concentrations of E in plasma were over the MICs for most of the erythromycin-sensitive bacteria (0.5 micrograms/ml) in 7 out of 10 patients (mean 0.66 micrograms/ml) at the end of the third dose interval. The drug concentrations in tissues were lower than in plasma (due to short treatment time of totally 24 h). The mean percentage of penetration (tissue/plasma ratios) for erythromycin ranged from 63 to 95% in various pelvic tissues. However, rather extensive interindividual variation was observed. The degree of hydrolysis of 2'-acetyl erythromycin to erythromycin was 29-39% in plasma and 42-73% in tissue samples. There were negligible amounts of inactive anhydro forms in plasma after EA and their concentrations in tissue samples were low, as well. PMID- 8447850 TI - Pharmacological properties of a new fluoroquinolone on the central nervous system in rodents. AB - The pharmacological effects of the novel fluoroquinolone 7-(1R,4R-2,5 diazebicyclo[2.2.1]heptan-2-yl)-1-(1,1-dimethyl )ethyl-6-fluoro - 4-oxo-1,4 dihydro-1,8-naphthyridine-3-carboxylic acid (BMY-40062, CAS 116143-32-9) on central nervous system were investigated in mice and rats, in comparison in some cases with those of reference quinolones. BMY-40062 showed no effect on general behavior, spontaneous activity, body temperature and neuromuscular coordination in rats at the doses of 1000 and 250 mg/kg. None of the quinolones tested including BMY-40062 modified the seizures induced by bicuculline, a specific GABA A antagonist. BMY-40062 and ciprofloxacin did not consistently influence the pentetrazol-induced convulsions. On the contrary, pefloxacin exhibited a marked convulsivant activity. In the fenbufen (non-steroidal anti-inflammatory drug) induced seizure model, BMY-40062 showed no effect. Enoxacin, norfloxacin followed by ciprofloxacin elicited a convulsivant effect in presence of fenbufen. Under these experimental conditions, BMY-40062 had no effect on the central nervous system compared to the other tested quinolones in rodents. PMID- 8447851 TI - General pharmacology of loracarbef in animals. AB - Loracarbef ((6R, 7S)-7-[(R)-2-amino-2-phenyl-acetamido]-3-chloro-8-oxo-1- azabicyclo [4.2.0]oct-2-ene-2-carboxylic acid, monohydrate, LY 163892, CAS 121961 22-6) is a carbacephem antibiotic targeted for use in the treatment of infectious disease. The potential pharmacological effects of this agent were examined on cardiovascular, respiratory, gastrointestinal, central nervous and autonomic nervous systems. Also examined were local anesthetic activity, effects on platelet aggregation, circulating blood glucose, primary antibody production, renal function, blood coagulation, ocular irritation, and the acute inflammatory response. Doses of 100, 1000, and 2000 mg/kg given by the oral route were selected for most in vivo studies. Concentrations up to 3 x 10(-3) mol/l were used in vitro. Loracarbef was essentially inactive in the tests of central and autonomic nervous system function, platelet aggregation, renal function, blood hemolysis, primary antibody production, blood coagulation, and ocular irritation. It had no local anesthetic activity. At high oral or intravenous doses, representing significant multiples of the therapeutic dose, loracarbef caused changes in gastrointestinal (decrease in gastric acid production and gastric fluid volume; increased biliary output), cardiovascular (increased mean pressure, cardiac output, heart rate, and femoral flow), blood glucose (increased glucose levels), and anti-inflammatory tests (suppressed acute inflammatory response). In summary, loracarbef exhibited minimal activity in these pharmacodynamic studies. These results indicate loracarbef has a low potential to produce adverse effects at therapeutic doses. PMID- 8447852 TI - Comparative stability of carbapenem and penem antibiotics to renal dehydropeptidase-I. AB - Comparison has been made on the stability of 4 carbapenems and 3 penems against porcine renal dehydropeptidase-I (DHP-I). Evaluated were the carbapenems (5R,6S) 3-[[2-(formimidoylamino)ethyl]thio]-6-[(R)-1-hydroxyethyl] - 7-oxo-1 azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid monohydrate, CAS 74431-23-5, in the following called FAC, (5R,6S)-3-[(S)-1-(acetimidoylpyrrolidin-3-yl)thio]-6-[(R)-1 hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0] hept-2-ene-2-carboxylic acid, CAS 87726 17-8, in the following called AHC, (4R,5S,6S)-3-[[(3S,5S)-5 dimethylcarbamoylpyrrolidin-3-yl]thio]-6- [(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1 azabicyclo[3.2.0]hept-2-ene-2- carboxylic acid trihydrate, CAS 96036-03-2, in the following called DHC. (1R,5S,6S)-2-[(6,7-dihydro-5H-pyrazolo[1,2-a] [1,2,4]triazolium-6-yl)thio]-6-[(R)-1-hydroxyethyl]-1-methyl-ca rbapen - 2-em-3 carboxylate, in the following called DHM, and the penems (5R,6S)-6-[(R)-1 hydroxyethyl]-7-oxo-3-[(R)-2-tetrahydrofuryl]-4-thia-1 - azabicyclo [3.2.0]hept-2 ene-2-carboxylic acid sodium salt, in the following called HTC, (5R,6S)-2 carbamoyloxymethyl-6-[(1R)-hydroxyethyl]-2-penem-3-carboxylic acid, in the following called CHC, (5R,6S)-6-[(R)-1-hydroxyethyl]-3-[(3S)-(cis-1 oxotetrahydrothiophen++ +-3-yl) thio]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene 2-carboxylic acid, in the following called HHC. According to the comparison of the Vmax/Km ratios, the order of stability of the compounds to hydrolysis by renal DHP-I was as follows: DHM >> DHC > HHC > AHC > HTC > CHC > FAC. From this result it is particularly noteworthy that DHM has extremely high stability against renal DHP-I. PMID- 8447853 TI - New algorithm for analysis of data obtained by means of circular dichroism titration method. AB - A new method for analysis of circular dichroism titration data used for drug protein binding investigations is proposed. A square equation between molar ellipticity change and total drug concentration is obtained which is examined analytically. A new minimization algorithm for determining the binding sites and association constants of each type of drug-protein complexes is applied. PMID- 8447854 TI - ASHA 1993 reference issue. PMID- 8447855 TI - Employee satisfaction with occupational health services: results of a survey. AB - Employee satisfaction with occupational health care services can be one important indicator of quality of care. Satisfaction assessment can provide feedback to improve health care services and utilization. Employee satisfaction with health care services may be a reflection of the value the company places on health care and safety. PMID- 8447856 TI - The resurgence of tuberculosis: risk in health care settings. AB - After many years of steady decline in reported cases, TB is resurging in the U.S. as a clinical problem and a public health problem. TB continues to be an occupational hazard for health care workers and others in work environments where spaces are enclosed, ventilation is poor, and personnel are crowded. Transmission occurs by inhaling droplet nuclei generated by persons with active TB. Education, active surveillance, reporting, and an expanded role in community action are appropriate roles for the occupational health nurse. PMID- 8447857 TI - Factors associated with male workers' engagement in physical activity: white collar vs. blue collar workers. AB - The purpose of this study was to identify factors associated with male workers' participation in different kinds of physical activity, noting differences between white collar and blue collar workers. This study examined the variables, perceived health status, self efficacy, perceived barriers, age, education, income, and job category (Pender, 1987) for their association with physical activity. Self efficacy and perceived health status were the cognitive-perceptual factors that predicted physical activity. Job category (e.g., blue collar vs. white collar) was found to be a highly significant predictor of physical activity. Comparing physical job requirements with the individual worker capacity can suggest to the occupational health nurse physical fitness programs that are most appropriate for individual workers. PMID- 8447858 TI - Occupational health nursing practice in the United Kingdom: the European influence. AB - Legislation introduced by the European Parliament has markedly affected the practice, education, and training of occupational health nurses. New health and safety legislation requires occupational health nurses to demonstrate and prove their competence to perform certain duties. The statutory body must create, for the first time, a definition of an occupational health nurse. A special body has been established to produce standard vocational qualifications for all workers. Occupational health nurses are the first members of the nursing profession to be involved in the process. PMID- 8447859 TI - Elements of a comprehensive absenteeism control program: role of the occupational health nurse. AB - Absence from work costs American companies more than $40 billion annually. Absenteeism control programs can be cost effective, but relatively few companies in the U.S. seem to have comprehensive programs. Key elements in a comprehensive program include return to work opportunities, careful job design, standards for expected times off, clear administrative responsibility for communicating with absent employees and health care providers, and an effective information system. Perhaps the most important factor in a successful program is employee centered management and a corporate philosophy that views employees as assets. The occupational health nurse is ideally suited by education, knowledge, and job function to lead the design and management of a comprehensive absenteeism control program. PMID- 8447860 TI - Legal challenges of tuberculosis in the workplace. PMID- 8447861 TI - Evaporation versus iced peritoneal lavage treatment of heatstroke: comparative efficacy in a canine model. AB - The authors compared the speed of cooling and treatment efficacy for evaporative cooling versus iced peritoneal lavage in a canine heatstroke model. Nine random source, mongrel dogs were anesthetized, shaved, and internally heated until the core temperature reached 43.0 degrees C. The animals were then randomly assigned to be cooled to 37 degrees C either by sterile normal saline (6 degrees C) continuous peritoneal lavage at 250 mL/min (n = 4), or by spraying with tap water (15 degrees C, 12 L/min) before a large fan blowing room temperature air (23 degrees C) across the dog at 0.5 m/sec from a height of 50 cm (n = 5). Temperatures were monitored by thermocouples in both tympanic membranes. Electrocardiogram, blood pressure, and pulse were continuously monitored. Evaporative cooling was as rapid as iced peritoneal lavage (0.18 +/- .03 versus 0.17 +/- .07 degrees C/min/m2, P = NS). All animals survived, although one animal in each treatment group demonstrated a moderate neurologic deficit when measured 48 hours following resuscitation. A simple noninvasive evaporative cooling technique, readily available in the emergency department, appears to be as rapid readily available in the emergency department, appears to be as rapid and effective as aggressive peritoneal lavage for cooling and treating heatstroke in the dog. PMID- 8447862 TI - Are aluminum foreign bodies detectable radiographically? AB - To determine whether aluminum foreign bodies located in the soft tissues of small body parts are radiopaque, six pieces of aluminum (0.5 mm x 0.5 mm x 1 mm; 0.5 mm x 0.5 mm x 2 mm; 0.5 mm x 0.5 mm x 4 mm; 1 mm x 1 mm x 1 mm; 1 mm x 1 mm x 2 mm; and 1 mm x 1 mm x 4 mm in size) were placed in a chicken wing model and anteroposterior and lateral radiographs of the preparation were obtained. Aluminum fragments (of all sizes used) were easily discernible when projected away from bone. The authors conclude that aluminum foreign bodies located in the soft tissues of small body parts are radiopaque. PMID- 8447863 TI - Surveillance of poisoning and drug overdose through hospital discharge coding, poison control center reporting, and the Drug Abuse Warning Network. AB - There is no gold standard for determining poisoning incidence. We wished to compare four measures of poisoning incidence: International Classification of Diseases 9th Revision (ICD-9) principal (N-code) and supplemental external cause of injury (E-code) designations, poison control center (PCC) reporting, and detection by the Drug Abuse Warning Network (DAWN). We studied a case series at two urban hospitals. We assigned ICD-9 N-code and E-code classifications, determining whether these matched with medical records. We ascertained PCC and DAWN system reporting. A total of 724 subjects met entry criteria; 533 were studied (74%). We matched poisoning N-codes for 278 patients (52%), E-code by cause in 306 patients (57%), and E-code by intent in 171 patients (32%). A total of 383 patients (72%) received any poisoning N-code or any E-code. We found that PCC and DAWN reporting occurred for 123 of all patients (23%) and 399 of 487 eligible patients (82%), respectively. In multiple logistic regression, factors of age, hospital admission, suicidal intent, principal poisoning or overdose type, and mixed drug overdose were statistically significant predictors of case match or report varying by surveillance measure. Our findings indicate that common surveillance measures of poisoning and drug overdose may systematically undercount morbidity. PMID- 8447864 TI - Potential use of warm butyl alcohol vapor as adjunct agent in the emergency treatment of sea water wet near-drowning. AB - The short-term course of sea water wet near-drowning was studied in anesthetized rabbits breathing spontaneously. Therapeutic trials were incorporated using warm n-butyl alcohol vapor both in inspired air and in inspired oxygen. The purpose was to determine if butyl alcohol vapor might alleviate the hypoxemia of sea water aspiration, possibly by a defoaming action on the fine foam bubbles of alveolar origin in the lung edema even without tracheal foam being present. The findings from 20 rabbits without overt tracheal foam, that had aspirated 2.05 mL/kg of sea water and were placed 10-minutes postaspirationally into four different inhalational treatment groups, showed remarkable differences. Warm butyl alcohol vapor made by humidification of 7.5% solution at 31 degrees C alleviated the hypoxemia. With vapor treatment for 15 minutes, mean arterial oxygen tension (PaO2) was not significantly changed in the water vapor-air group, but increased significantly to 50.5 +/- 4.6, 70.0 +/- 8.9, and 146.7 +/- 40.7 mm Hg in the butanol/water vapor-air, water vapor-oxygen, and butanol/water vapor oxygen groups, respectively. With treatment for 30 minutes, mean PaO2 increased to 248.3 +/- 38.0 mm Hg with butanol/water vapor-oxygen inhalations, but only to 91.2 +/- 9.8 mm Hg with 100% water vapor-oxygen inhalations. Thus, the inspired vapor of butanol was much more effective in elevation of arterial blood oxygen pressures when combined with oxygen therapy over the values found when 100% water vapor-oxygen treatments were given. Respiratory and cardiac depressant effects from inspired butanol were not evident.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447865 TI - Equity buy-in structures of emergency medical group practice. AB - The authors polled emergency medicine groups in an attempt to identify whether equity was offered and the time, costs, and methods of achieving equity. Several characteristics of equity and nonequity groups were compared. A survey was distributed to 514 groups from a list identified by the American College of Emergency Physicians. Nonresponders received a second mailing. Valid responses were received from 127 groups representing 3,405 physicians. Of the respondent groups, 69 allowed full equity participation. The mean time to full partnership was 2.2 years for new physicians. Single hospital groups tended to have shorter (1.6 years) buy-in periods compared with multihospital groups (3-4 years). The most common method of buy-in was a differential in the "bonus" structure between new physicians and partners. The actual cost to attain full equity varied greatly with a range of from $0 to $500,000. Groups not owning their accounts receivable had a total mean buy-in cost of approximately $40,000 as compared with those that did own their accounts receivable, where the average buy-in cost was approximately $106,000. The proportion of equity groups that had two thirds or more physicians board-certified in emergency medicine was significantly greater than those groups without equity. The detailed structure for attaining equity varied greatly between groups. The authors conclude that many emergency physician groups allow full equity participation. The average time to full partnership is generally less than 3 years. There are many diverse schemes of entering into partnership. The cost of acquiring full equity varies greatly. PMID- 8447866 TI - Inadvertent intubation of the left mainstem bronchus. AB - This is a case report of a previously healthy 61-year-old white male who was emergently intubated in the field by paramedical personnel and transported to the emergency department. Physical examination revealed minimal-to-absent breath sounds over the right hemithorax associated with cyanosis of the head, face, and upper extremities. Emergency needle decompression of the right lung was accomplished without improvement. A postmortem chest radiograph revealed a left mainstem bronchus intubation. Use of the physical examination, the endotracheal tube depth, and an awareness of the possible--but rare-complication of left mainstem bronchus intubation may lead to accurate diagnosis and treatment and avoid unnecessary procedures. PMID- 8447867 TI - "Crack" cocaine-induced bilateral amblyopia. AB - Illicit use of cocaine has been associated with adverse vascular events involving most organ systems. A case report of a 30-year-old female with acute, bilateral loss of vision after smoking "crack" cocaine is presented. Other adverse ocular manifestations of cocaine use, and the differential diagnosis of toxin-induced blindness are presented. PMID- 8447868 TI - Air bags: lifesaving with toxic potential? AB - Federal Motor Vehicle Safety Standard No. 208, "Occupant Crash Protection", requires that all passenger cars manufactured after September 1, 1989 be equipped with automatic crash protection. Car manufacturers met this requirement by installing automatic safety belts or air bags. No chemical injuries have been reported as a result of air bag deployment in motor vehicle accidents (MVA). A 6 month retrospective study was conducted to evaluate the toxic effects of the white powdery residue from air bags, a combination of talc and sodium hydroxide, found in the driver compartment after an MVA. The study reviewed time to onset of symptoms, symptomatology, and treatment. The study included seven patients exposed to deployed air bags after an MVA. Four cases resulted in dermal burns and three patients were diagnosed with unrelated injuries. Three patients presented to an emergency department within 48 hours of the exposure complaining of burns to the skin. Two patients attempted home therapy but became concerned when the symptoms did not subside. One patient was discharged with the diagnosis of first degree burns of the chin and left hand. Another patient experienced bilateral hand erythema and blisters. Standard burn therapy was instituted in both instances. A third patient arrived 1 hour post-exposure to the emergency department complaining of a burning sensation to the hands, but the skin appeared normal. Thorough irrigation was initiated and Silvadene (Marion, Kansas City, MO) applied. One patient notified the poison center 1 hour post-exposure complaining of erythema and burning to his hands after an MVA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447869 TI - Protective effects of a prostaglandin oligomer on rats exposed to hypoxia. AB - To study the protective effects of a prostaglandin E1 oligomer against hypoxia, hypoxia was induced in artificially ventilated rats by replacing the air with 100% nitrogen under anesthesia. Parameters such as survival rate, blood pressure, electrocardiogram, blood lactate, glucose, pH, PO2, PCO2, intracellular adenosine triphosphate, and mitochondrial function were studied. A hypoxia time of 3.5 minutes reduced the survival rate to 50%. However, the prehypoxic administration of 6.0 mg/kg of MR-356, an oligomer synthesized from prostaglandin E1, improved the survival rate to 90%. Similar beneficial effects were also observed when MR 356 was administered either 2 minutes after the start of hypoxia or 30 seconds before the cessation of hypoxia. Systemic parameters were not changed by the administration of the oligomer. The mechanism of action of the oligomer may be to protect membranes during hypoxic insult. PMID- 8447870 TI - Vaginal bleeding secondary to an aborting uterine leiomyoma. AB - The authors present the case of a young woman who presented to the emergency department with vaginal bleeding and an "aborting" uterine leiomyoma. Although well described in the gynecologic literature, this phenomenon is not commonly seen in the emergency department, nor is it well described in the emergency medicine literature. The case highlights the importance of a thorough pelvic examination in all women presenting with a complaint of vaginal bleeding, and in addition it describes an atypical presentation for uterine leiomyomas. PMID- 8447871 TI - Cold-induced urticaria and angioedema: diagnosis and management. AB - The physical urticarias compromise a heterogeneous group of disorders characterized by their propensity to form urticarial lesions after exposure to certain physical stimuli, such as heat, vibration, or cold. Although generally benign, systemic hypotension and angioedematous airway compromise are known life threatening complications. We present the case of a man who experienced benign angioedematous changes in response to cold exposure, and discuss the clinical course, diagnosis, and management of cold urticaria. PMID- 8447872 TI - Bronchial stump disruption following inadvertent right mainstem intubation 9 years after pneumonectomy. AB - An 82-year-old man, with a history of right pneumonectomy 9 years prior to admission, was emergently intubated for respiratory failure resulting from rapid atrial fibrillation and congestive heart failure. Postintubation chest radiograph demonstrated the tube to be in the right bronchial stump. Over the next 48 hours gas exchange remained poor, endotracheal suctioning produced copious serosanguinous secretions, and chest radiographs showed increasing air, with air fluid levels, in the previously opacified right hemithorax. Bronchoscopy demonstrated air bubbling from the posterior wall of the right bronchial stump, consistent with a bronchopleural fistula. The authors conclude that right mainstem intubation, in the setting of a previous right pneumonectomy, can lead to disruption of the bronchial stump with drainage of fluid from the postpneumonectomy space into the functioning left lung with severe compromise of gas exchange. PMID- 8447873 TI - Ultrasound documentation of spontaneously resolving appendicitis. AB - Diagnostic ultrasound has been reported to be a highly specific technique for the confirmation of acute appendicitis. The authors report the case of a 27-year-old male who presented with clinical, laboratory, and classic ultrasound findings indicating early acute appendicitis. The patient's condition resolved spontaneously without operative intervention, and repeat sonography 2 weeks later was entirely normal. Ultrasound examination may allow documentation of spontaneously resolving appendicitis. PMID- 8447874 TI - Continuous 12-lead electrocardiograph monitoring in the emergency department. AB - Many patients presenting to the emergency department with suspected acute myocardial infarction have an initial electrocardiogram (ECG) non-diagnostic for acute injury or ischemia. Continuous ST segment monitoring devices have been used by physicians in the past to diagnose ischemia in the ambulatory outpatient population and to identify coronary occlusion in postthrombolytic and postsurgical patients. We report three patients with suspected acute myocardial infarction who underwent real-time continuous 12-lead ST segment monitoring with frequent serial ECGs on a microprocessor-controlled device during their initial emergency department evaluation. Continuous 12-lead ECG monitoring revealed significant changes on the ECG in all three cases presented, with a resultant change in emergency department therapy. Interestingly, all of these patients had significant ECG changes in the absence of recurrence of chest pain. We believe real-time continuous 12-lead ST segment monitoring with frequent serial ECGs can identify patients with an initially nondiagnostic or atypical ECG who may benefit from early interventional therapy. PMID- 8447875 TI - Luxation of the globe. AB - Emergency physicians encounter globe luxation, anterior dislocation of the eyeball beyond retracted lids, in a limited number of clinical circumstances. The authors present a case of spontaneous luxation followed by a general discussion of luxation. An understanding of the pathophysiology of various causes of luxation and the appropriate method and timing of reduction allows appropriate evaluation, treatment, and follow-up, thereby limiting patient discomfort, recurrence, and perhaps long-term visual impairment. PMID- 8447876 TI - Arterial emboli of the upper extremity presenting as ischemic heart disease: case report and review. AB - A case of brachial artery embolism presenting as ischemic coronary artery disease is presented. The patient presented with sudden onset of left arm pain, shortness of breath, nausea, vomiting, and diaphoresis. Initial relief with sublingual nitroglycerin was seen. With further evaluation, a brachial artery embolus was diagnosed, and an embolectomy was successfully performed. Delay in diagnosis and treatment can lead to substantial morbidity, including gangrene and amputation. Misdiagnosis is common, as it is seen in the same patients at risk for ischemic heart disease, stroke, and other vascular abnormalities. An awareness of this problem is important among those who initially evaluate patients in emergency departments. PMID- 8447877 TI - Scanned emergency department to emergency department image transfer (SEE-IT): implementation and standardizing protocols to optimize tertiary referrals. PMID- 8447878 TI - Spurious laboratory values in diabetic ketoacidosis and hyperlipidemia. PMID- 8447880 TI - The lowly nasogastric tube: still appropriate after all these years (at times). PMID- 8447879 TI - Computerized monitoring of emergency department patient flow. AB - To demonstrate the use of the computer as a tool for information storage and analysis in the emergency department (ED) with the objective of improving ED efficiency, the authors conducted a prospective study from April through September 1991. Information from charts of patients who came into the medical emergency department (MED) and surgical emergency department (SED) were checked and input into the computer. This information included triage classification, registration time, time seen, disposition, disposition time, physician's impression as well as the reasons for delayed disposition. For the 7,086 patients who entered the MED in this period, the waiting time from registration to seeing a physician was (three shifts, triage 3 and 4 patients, respectively) 37.47, 29.52, and 20.61 minutes; and 42.54, 35.85, and 18.75 minutes. Triage 3 and 4 patients comprised 69.42% and 12.41% of the total patients seen. However, of the 4,545 patients who entered the SED, the waiting time for triage 3 and 4 patients (79.23% and 9.79% of total, respectively) was 9.22 and 9.88 minutes, respectively. Disposition time was 2.3 to 3.3 hours in MED and 2.0 to 5.5 hours in SED. Reasons for delayed disposition in both MED and SED included finishing intravenous fluid, waiting for consultation, waiting for computed tomography available, and waiting for sonography available. A commitment to providing quality care in the ED sometimes results in unreasonable waiting times for triage 3 and 4 patients, causing patient dissatisfaction. Readjustment of staffing and space use is needed. Equipping the ED with facilities to provide sonography and computed tomography would enhance patient flow; this needs further study to evaluate cost effectiveness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447881 TI - Multiple midline abdominal injuries along the lumbar column. PMID- 8447882 TI - All things to all people all the time. PMID- 8447883 TI - Case report: intracranial penetration of a nasogastric tube. PMID- 8447884 TI - Cocaine-induced ventricular arrhythmias and rapid atrial fibrillation temporally related to naloxone administration. PMID- 8447885 TI - Alternative training in emergency medicine. PMID- 8447886 TI - AAMC policy on the generalist physician. AB - In 1992 the Association of American Medical Colleges created the Generalist Physician Task Force to develop a policy statement for the AAMC and to recommend ways to help reverse the trend away from generalism. The task force strongly endorsed using private-sector initiatives exerted through consensus and voluntary cooperation, although recognizing the indispensable role of government in defining the magnitude of the need for generalist physicians and in eliminating barriers to meeting the need. As a policy, the AAMC advocates an overall national goal that a majority of graduating medical students be committed to generalist careers (family medicine, general internal medicine, or general pediatrics) and that appropriate efforts be made by all schools so that this goal can be reached within the shortest possible time. To further this goal, the task force recommended strategies for the AAMC, schools of medicine, graduate medical education, and the practice environment. PMID- 8447887 TI - Introducing physician order entry at a major academic medical center: I. Impact on organizational culture and behavior. AB - In 1988 the University of Virginia Medical Center began implementation of a medical information system based on mandatory physician order entry. The implementation process was much more difficult than expected. The program experienced considerable delays, and cost much more than was originally estimated. Although there were some legitimate questions concerning the user friendliness of the new technology, these were less significant than the cultural and behavioral problems encountered. The new system challenged basic institutional assumptions; it disturbed traditional patterns of conduct and forced people to modify established practice routines. Real progress toward the integration of the system into the center's operational culture occurred only after a senior management team representing important sectors of the hospital staff and administration began meeting regularly to address the institution-wide issues that had been raised. The author describes the problems that occurred and the organizational behaviors on which they were based, analyzes the lessons learned, documents the progress that has been achieved, and outlines the challenges that remain. The center's experience provides insight into the issue of technology-driven organizational transformation in academic medical centers. Recommendations for successful introduction of similar agents of institutional change are presented. PMID- 8447888 TI - Introducing physician order entry at a major academic medical center: II. Impact on medical education. AB - The introduction of an information technology (IT) system that mandates order entry by physicians had significant and often unexpected effects on medical education at the University of Virginia Medical Center. The system was deactivated briefly after the introduction of laboratory ordering, and frustration with the pharmacy ordering pathways provoked a major confrontation between the residents and medical center management. With time and experience, however, the housestaff have adjusted to the system and developed facility in using it. Much of the dissatisfaction was derived from the perception that "doctors spend too much time on the computer." In fact, less than 10% of the physicians spent more than an hour each day. However, a small group of residents on call for the busier services were sometimes at the computer for more than four hours each day. Changes in responsibilities, patterns, and priorities of work introduced by the system also contributed significantly to the general dissatisfaction. These issues had not been thoroughly considered in the planning stage, but it was only after accommodation was made to these changes that integration of the technology into routine practice could proceed. The author emphasizes the importance of extensive involvement and leadership of attending physicians in the planning and implementation of such a system. He presents a set of recommendations to those considering similar IT initiatives and wishing to reduce the disruptions that may accompany their introduction. PMID- 8447889 TI - A view of medical practice in 2020 and its implications for medical school admission. PMID- 8447890 TI - The desktop database dilemma. PMID- 8447891 TI - A general and primary solution for American health care problems. PMID- 8447892 TI - Is the American system preparing the right kind of physicians? PMID- 8447893 TI - Every medical school must have a department of family practice. PMID- 8447894 TI - Fostering new career directions for physicians at George Washington University. PMID- 8447895 TI - Never too late to learn: a senior surgeon's observations of CME in Toronto clinics. PMID- 8447896 TI - Problem-based learning: a review of literature on its outcomes and implementation issues. AB - The effects of problem-based learning (PBL) were examined by conducting a meta analysis-type review of the English-language international literature from 1972 to 1992. Compared with conventional instruction, PBL, as suggested by the findings, is more nurturing and enjoyable; PBL graduates perform as well, and sometimes better, on clinical examinations and faculty evaluations; and they are more likely to enter family medicine. Further, faculty tend to enjoy teaching using PBL. However, PBL students in a few instances scored lower on basic sciences examinations and viewed themselves as less well prepared in the basic sciences than were their conventionally trained counterparts. PBL graduates tended to engage in backward reasoning rather than the forward reasoning experts engage in, and there appeared to be gaps in their cognitive knowledge base that could affect practice outcomes. The costs of PBL may slow its implementation in schools with class sizes larger than 100. While weaknesses in the criteria used to assess the outcomes of PBL and general weaknesses in study design limit the confidence one can give conclusions drawn from the literature, the authors recommend that caution be exercised in making comprehensive, curriculum-wide conversions to PBL until more is learned about (1) the extent to which faculty should direct students throughout medical training, (2) PBL methods that are less costly, (3) cognitive-processing weaknesses shown by PBL students, and (4) the apparent high resource utilization by PBL graduates. PMID- 8447897 TI - Litigation involving medical faculty and academic medical centers, 1950-1991. AB - An analysis is presented of 240 cases of litigation involving medical faculty, medical schools, and academic medical centers reported over the period 1950-1991. The number of reported cases increased dramatically over the study period in association with the expansion of the national medical educational enterprise. These cases can be conveniently divided by the issues they dealt with into three broad areas: general administration (89 cases), clinical affairs (108 cases), and research issues (43 cases). Cases of litigation related to general administration were most often concerned with the hiring, promotion and/or tenure, and discharge of faculty, with nearly half of these alleging discrimination. General administrative disputes also arose over allocation of departmental resources and responsibilities, faculty conduct, Veterans Affairs, relationships, employee benefits, system-wide discrimination, and collective bargaining. Courts generally supported the exercise of administrative discretion, yet examined procedures carefully. Litigation related to clinical affairs increased dramatically in recent years. Issues litigated reflect the complexity of the existing academic health care system and environment: sovereign immunity and/or malpractice, practice plans, staff privileges, indemnification, access to peer review records or other records, and conduct of practice. Outcomes of clinically related litigation through 1991 indicate substantial leeway for medical faculty, medical schools, and academic medical centers to innovate and advance their patient mission. Litigation related to medical research also accelerated recently. Issues litigated involved grants and/or personnel management, research risks, commercialization, research funding, ethics, and research animals. Litigation has paralleled (1) federal policy initiatives designed to stimulate collaboration between industry and academia and (2) the growth of regulations designed to monitor policy areas affecting research. The exposure of academic medical administrators and faculty to litigation has increased in the last 40 years. Medical schools and academic medical centers should take active steps to reduce future risks of litigation. PMID- 8447898 TI - Longitudinal comparison of the academic performances of Asian-American and white medical students. AB - PURPOSE: To compare the academic performances of Asian-American medical students- before, during, and after medical school--with those of white students. METHOD: The 140 Asian-American graduates and 2,269 white graduates from the classes of 1981-1992 at Jefferson Medical College were studied prospectively: data on academic performance, indebtedness, and delayed graduation were analyzed and compared for all the graduates. F-tests, chi-square tests, and regression models were used. RESULTS: The Asian-Americans had statistically significantly higher scores on the SAT (Scholastic Aptitude Test) quantitative subtest and on the MCAT (Medical College Admission Test) chemistry, physics, and science problems subtests; the whites had significantly higher scores on the MCAT reading subtest; third-year grade-point averages for required clerkships; and scores on National Board of Medical Examiners Part I, II, and III examinations (NBME I, II, and III). No significant difference was found in the other performance measures, including ratings in the first year of residency. Regression analysis showed that the MCAT reading score was the major predictor of Asian-Americans' performances on the NBME I and II. CONCLUSION: Because the MCAT reading score is the major predictor of later performance for Asian-American students, schools should consider employing different criteria in predicting and monitoring these students' performances. PMID- 8447899 TI - Medical school policies regarding medical students and HIV infection. AB - PURPOSE: To ascertain how medical schools address several difficult policy issues regarding medical students and HIV (human immunodeficiency virus), and to examine whether schools' policies differ according to the incidences of HIV in the schools' locations. METHOD: Between January 5, 1990, and March 20, 1991, 15 minute telephone interviews were conducted with spokespersons (deans or other policymakers) at 42 U.S. medical schools: the 14 in areas of high incidence of HIV, the ten in areas of low incidence, and a convenience sample of 18 in areas of medium incidence. The interview questions were about preventing HIV infection, reporting HIV infection, confidentiality, screening for HIV infection, limiting clinical activities, counseling, hepatitis B vaccination, prophylactic zidovudine administration, and disability and health insurance. RESULTS: A total of 16 schools, including seven of the 14 in high-incidence areas, had no policy regarding medical students with HIV infection. No strong statistically significant difference was found between the responses of schools in low incidence areas and those of schools in high-incidence areas. No medical school routinely tested its students for HIV. CONCLUSIONS: Schools should do more to ensure that students remember and follow the guidelines about preventing occupational exposure to HIV; in addition, prior to screening for HIV, schools should ensure that students are provided with appropriate levels of health, life, and disability insurance. PMID- 8447900 TI - Prevalences of ethics, socioeconomics, and legal education requirements for residency training. PMID- 8447901 TI - Anxieties of entering first-year residents. PMID- 8447902 TI - Practicing pediatricians' views of the child's role in the pediatric interview. PMID- 8447903 TI - Medical school financing: comparing different types of schools and departments. PMID- 8447904 TI - The past as prologue. AB - What has the Association of American Medical Colleges (AAMC) accomplished in the last 25 years in its efforts to advance medical education, biomedical research, and health delivery in this country? Can the AAMC's past accomplishments help predict how it will respond to future challenges? To answer these questions, the author traces in detail the recent history of the AAMC, focusing on the expansion of the association's role and constituencies and how these and other changes were precipitated by recommendations in the AAMC's 1965 "Coggeshall Report." He also recounts how the AAMC has responded to the pressures and needs of recent years (such as fostering an increase in the number of practicing physicians) and describes in detail the organization and functions of the AAMC's staff, with emphasis on its six divisions and the fact that many of the complex issues that confront the AAMC transcend the boundaries of governance councils and staff divisions and dictate that association policy be based on broad consensus. Looking ahead, he sees at least four important activities that the AAMC will continue to be involved with: fostering the education of more minority students; promoting health services research; finding an appropriate role in the evolution of health care reform; and addressing the need for academic medicine to be more socially responsive. The author concludes that the AAMC's highly regarded record, its organization, and its financial stability all indicate that it will do well as it tackles the issues on the horizon and others not yet in view.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447905 TI - Beyond "health care reform". AB - The author discusses the need to make corrections in the U.S. health care system, describes the simplistic and money-oriented definition that many persons have of "health care reform," and discusses the issues he thinks will and will not be dealt with in the coming reforms of the health care system. He maintains that true reform would deal with matters such as restraining expansion of the health care industry, setting reasonable fees, and confronting the harmful social and environmental conditions that result in high "medical" care costs and poor health statistics. The medical profession--including academic medical centers--has a large role to play in true health care reform, which will involve facing the major barriers (which he outlines) that are now impeding important reforms (e.g., increasing the number of generalist physicians; finding better ways to pay for medical students' and residents' education). The profession cannot make progress in true reform without developing a vision of what the U.S. health care system should be and becoming active in moving toward that vision, acting in the interests of both the individual patient and the community as a whole. The author outlines some of the barriers to finding that vision (such as the influence of third-party payers on the doctor-patient relationship and the fragmentation of medicine and medical education by specialties and subspecialties) and proposes the characteristics and values of the kind of medical education and community involvement of academic medical centers that can help create the needed vision, regain the trust of the public, and thereby reform health care in the interests of both the community and the profession. PMID- 8447906 TI - The medical school curriculum committee revisited. AB - Numerous study commissions have contended that departmental territoriality and lack of coordinated planning are stagnating contemporary medical education. As a cure, these commissions have recommended the creation of centralized academic management units empowered to oversee revitalization of the curriculum through a series of reforms, including better definition of graduation competencies, community-based training, interdisciplinary courses, problem-based learning, and modernization of evaluation strategies. To determine the extent to which these recommendations were being adopted, in 1990 the authors sent a questionnaire on curriculum committee functions, current innovation efforts, and future priorities to academic administrators and members of medical school curriculum committees at 143 North American medical schools. Responses were received from administrators (primarily associate deans for academic affairs) at 118 schools and committee members (primarily faculty) at 111 schools. Recommendations for enhancing curriculum committee effectiveness were also elicited. The authors conclude that centralization of curricular management has occurred at very few institutions, and that the commonly mentioned reforms are being adopted at a modest pace. The results are analyzed in light of theories of the institutional change process and strategies for introducing educational innovations into established institutions. PMID- 8447907 TI - An innovative faculty appointment system at the University of Nebraska. PMID- 8447908 TI - The high-priority/low-fat diet: a reduction plan for the federal deficit. PMID- 8447909 TI - The R.W. Johnson report: misguided reform of the basic sciences curriculum. PMID- 8447910 TI - Assessing the resources needed to provide ambulatory care experiences to medical students. PMID- 8447911 TI - Facilitator expertise and problem-based learning in PBL and traditional curricula. PMID- 8447912 TI - A credentialing program for surgery residents. PMID- 8447914 TI - Preparing medical libraries for use by students in PBL curricula. PMID- 8447913 TI - Predictors of black students' board performances: MCAT scores are not the whole story. PMID- 8447915 TI - Experience with pregnant physicians has been a good teacher. PMID- 8447916 TI - Problem effectiveness in a course using problem-based learning. AB - BACKGROUND: Problem-based learning (PBL) emphasizes active generation of learning issues by students. Both students and teachers, however, tend to worry that not all important knowledge will be acquired. To explore this question, problem effectiveness (i.e., for each problem, the degree of correspondence between student-generated learning issues and present faculty objectives) was examined in three interdependent studies. METHOD: The three studies used the same participants: about 120 second-year students and 12 faculty tutors in a six-week course on normal pregnancy, delivery, and child development at the medical school of the University of Limburg in The Netherlands, 1990-91. The participants were randomly assigned to 12 tutorial groups that were each given the same 12 problems; the problems were based on 51 faculty objectives; the tutors were asked to record all learning issues generated by their groups. Study 1 addressed this question: To what degree are faculty objectives reflected by student-generated learning issues? Study 2: To what extent do students miss certain objectives, and are these objectives classifiable? Study 3: Do students generate learning issues not expected by the faculty, and are these issues relevant to course content, and finally, why do students generate these issues? To help answer these questions, the studies employed expert raters and a teacher familiar with the course content. RESULTS: Study 1: For the set of 12 problems, the average overlap between learning issues and faculty objectives was 64.2% with the percentages for individual problems ranging from 27.7% to 100%. Study 2: Of the 51 objectives, 30 were not identified by at least one tutorial group; these objectives were grouped into three categories; on average, each group failed to identify 7.4 objectives (15%). Study 3: Of 520 learning issues, 32 (6%) were unexpected; 15 of these were judged to be at least fairly relevant to course content; they were grouped into four categories. CONCLUSIONS: The students' learning activities covered an average of 64% of the intended course content; in addition, the students generated learning issues not expected by the faculty, and half of these issues were judged relevant to the course content. Thus, PBL seems to permit students to adapt learning activities to their own needs and interests. PMID- 8447917 TI - Producing physician-scientists: a survey of graduates from the Harvard--MIT Program in Health Sciences and Technology. AB - BACKGROUND: The Harvard-MIT Program in Health Sciences and Technology (HST) is a flexible, preclinical curriculum, taught by members of the faculties of both Harvard University and the Massachusetts Institute of Technology, that stresses a rigorous, scientific, quantitative approach, small classes (usually fewer than 50 students), and student-faculty interaction. The program is aimed at students with strong backgrounds in quantitative and biological sciences who are interested in careers as physician-scientists. METHOD: The first 234 students of the program, who graduated between 1975 and 1985, were asked to participate in a 1990 follow up study by completing a four-page questionnaire and submitting curricula vitae and lists of publications, if available. Data were analyzed quantitatively and qualitatively. RESULTS: Of the 234 graduates, 211 (90%) responded. Sixty-three (30%) had received both MD and PhD degrees. The graduates were twice as likely to describe their primary professional roles as academic than as clinical practice; 94 held full-time faculty positions at 50 medical schools. The 154 (73%) in research spent an average of 51% of their time on this activity. According to the 179 graduates (85%) who stated that they would choose HST again, the most frequently mentioned reasons were the quantitative approach that emphasized integration of basic science and clinical practice (49%) and the small class size (37%). CONCLUSION: The HST MD curriculum, with its emphasis on basic science and research experience, has been successful in preparing carefully selected students for careers as physician-scientists, without necessarily requiring the completion of a PhD degree. PMID- 8447918 TI - Choices of training programs and career paths by women in internal medicine. AB - PURPOSE: To examine the choices of career paths of women in internal medicine, specifically to determine (1) whether women continue to prefer primary care practice more often than men do and (2) whether differences in career paths between men and women result from differences in the natures of the training programs they complete. METHOD: A database containing demographic, training, and clinical-practice information on 19,151 physicians (3,569 women and 15,582 men) who had been trained in internal medicine was constructed by merging data from the National Resident Matching Program matches in internal medicine for 1977-1982 with data from the 1985 American Medical Association Physician Masterfile, which contains physician practice profiles. RESULTS: Similar percentages of the men and the women chose primary care residencies (8% versus 9%, ns) and trained in the 100 major medical centers (49% versus 50%, ns). The women more frequently trained in programs affiliated with medical schools in the top prestige quartile (38% versus 33%, p < .05). The attrition rates of residents who left their training for careers in other medical fields were the same for the men and the women (14%). Fewer women obtained board certification (74% versus 80%, p < .01). The women chose to practice general internal medicine more frequently than did the men (52% versus 45%, p < .0001), regardless of the training program completed (primary care or traditional). CONCLUSION: The women pursued primary-care oriented internal medicine to a significantly greater degree than did the men, regardless of the type of training program completed (primary care or traditional). PMID- 8447919 TI - Station-length requirements for reliable performance-based examination scores. AB - PURPOSE: To directly compare the generalizability of medical students' performance scores under systematically varied station times in two surgery end of-clerkship performance-based examinations. METHOD: The participants were 36 third-year students randomly assigned to the first two rotations of the core surgery clerkship during 1991-92 at Southern Illinois University School of Medicine. The students rotated through a 12-station examination that employed standardized patients (SPs). In the first rotation, the student took six five minute stations and six ten-minute stations. In the second rotation, the time lengths were reversed for the same stations. The students' total scores were based on (1) subscores on checklists that were completed by the SPs and (2) subscores on the students' written responses to short questions about each station (these responses were provided at station couplets that were five minutes long, regardless of station length). Generalizability coefficients were computed from the pooled rotation results to provide reliabilities for scores from the two station lengths. RESULTS: Generalizability decreased in the ten-minute stations, mostly attributable to less variability among students' performances. The checklist subscores accounted for most of this variability, while couplet subscores remained stable between station lengths. CONCLUSION: The longer station length actually decreased the generalizability of the scores by decreasing the variability among students' performances; thus, allocating different times to stations can affect the score reliability, as well as impact on the overall testing time, of performance-based examinations. PMID- 8447920 TI - Students' premedical preparations and academic performances in medical school and residency. PMID- 8447921 TI - Influence of previous clerkship experiences on students' satisfaction with their current clerkship. PMID- 8447922 TI - Rural sources of medical students, and graduates' choice of rural practice. PMID- 8447923 TI - The optimal treatment of lymphoceles following renal transplantation. AB - Lymphoceles are well-recognized complications following kidney transplantation. The authors describe their experience with the treatment of eight clinically significant lymphoceles (incidence 2.7%). In seven patients percutaneous needle aspiration was attempted, often repeatedly, both for diagnostic and therapeutic purposes. In all of the patients the lymphocele recurred within days and internal marsupialization was therefore performed, in the last two patients utilizing minimal access surgery through laparoscopy. There were no postoperative complications or signs of a recurrence of the lymphocele. Patients following the laparoscopic marsupialization had a much briefer hospital stay and postoperative convalescence. Our results confirm that internal marsupialization is the procedure of choice for most post-transplant lymphoceles. Internal marsupialization through laparoscopy should be used in patients who meet the standard criteria for laparoscopy. PMID- 8447924 TI - Renal allograft artery stenosis: results of medical treatment and intervention. A retrospective analysis. AB - In a retrospective analysis of 1165 renal transplantations in our center, 65 cases of renal allograft artery stenosis were diagnosed angiographically (prevalence 5.5%). Hypertension was present in all cases; a bruit over the allograft and an increase in serum creatinine level were additional reasons for angiography. Shortly after diagnosis of the stenosis, two patients died and two others lost their grafts due to thrombosis. In 24 patients the decision was made not to correct the stenosis. One of these grafts was lost because the stenosis could not be corrected. Medical management of hypertension in these patients resulted in a decrease in diastolic blood pressure from 109 +/- 22 to 96 +/- 12 mm Hg (P < 0.01) 3 months after diagnosis with the use of almost twice as many antihypertensive drugs as at the time of diagnosis (P < 0.01). The stenosis was corrected if the angiography showed it to be so severe that it jeopardized renal allograft function or caused uncontrollable hypertension. Only three of nine percutaneous transluminal angioplasty (PTA) procedures resulted in a definitive correction of the stenosis. Surgical intervention was performed in 30 patients, including two patients whose PTAs had proved unsuccessful. Surgery led to graft loss due to thrombosis in 6 of 30 operations (20%), whereas restenosis occurred twice (7%). In three other cases (10%), the correction was not successful due to local anatomical variations or concomitant rejection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447925 TI - Duct-drained versus duct-occluded pancreatic grafts: a personal view. PMID- 8447926 TI - Comparison of intermittent injection of nondepolarizing solution with a single flush of UW solution for donor heart preservation. AB - Isolated canine hearts were preserved for 6 h at 5 degrees C followed by normothermic reperfusion for 2 h. The dogs were divided into two groups of nine hearts each; group 1 received a nondepolarizing preservation solution in multidose, and group 2 received a single flush of University of Wisconsin (UW) solution. Serum MB-CK and mitochondrial aspartate aminotransferase (m-AAT) concentrations and calcium overload during reperfusion were lower in group 1 than in group 2. At the end of reperfusion, myocardial ATP and total adenine nucleotide concentrations were higher and mitochondrial morphology appeared more intact in group 1 than in group 2. Left ventricular diastolic function was preserved better in group 1 than in group 2. These results suggest that in 6-h heart preservation, a nondepolarizing solution applied in multidose fashion protects the myocardium from the deleterious effects of hypothermia and cardioplegia better than a single flush of UW solution. PMID- 8447927 TI - Dissolving intravenous cyclosporin A in a fat emulsion carrier prevents acute renal side effects in the rat. AB - Cyclosporin A (CyA)-induced nephrotoxicity is still a serious clinical problem. The nephrotoxicity seems to be more pronounced when CyA (solubilized in water with Cremophore EL, as in Sandimmun) is given intravenously than when it is given orally. Using soybean oil in which CyA was dissolved, we prepared an intravenous fat emulsion without an artificial detergent, such as Cremophore EL. The renal effects of our new formula were compared with those of Sandimmun and Cremophore EL in a rat model. CyA in the fat emulsion did not significantly affect the glomerular filtration rate (GFR). Both Sandimmun and Cremophore EL significantly reduced the GFR. These results suggest that a change in the vehicle may obviate the acute nephrotoxic side effects caused by intravenous administration of CyA solubilized by Cremophore EL. PMID- 8447928 TI - The relationship of systemic hemodynamics and oxygen consumption to early allograft failure after liver transplantation. AB - The early postoperative hemodynamic data of 88 patients who underwent primary liver transplantation between July 1989 and October 1990 at the University Health Center of Pittsburgh were analyzed to establish the relationship of systemic hemodynamics and oxygen consumption to perioperative allograft function. The 15 patients whose allografts failed within the 1st month following transplantation were designated as group 1, while 73 patients who retained adequate graft function constituted group 2. Although the cardiac index and oxygen delivery did not differ significantly between the groups, group 1 consistently demonstrated a lower mean arterial pressure, oxygen consumption, arteriovenous oxygen content difference, and arterial ketone body ratio. The etiology of reduced oxygen consumption in group 1 patients is speculative, but the data support the notion that oxygen consumption is a useful, predictive indicator for liver allograft function after transplantation. PMID- 8447930 TI - Donor cell infiltration of recipient tissue as an indicator of small bowel allograft rejection in the rat. AB - This study assessed whether screening of host tissues for graft cells could be used as an effective monitor of rejection following small bowel transplantation. Allogeneic rat small bowel transplantation was performed with or without cyclosporin (CyA) immunosuppression and cellular infiltration of host tissues assessed by immunohistological staining. Without immunosuppression, grafts were completely rejected within 1 week. CyA treatment for 7 days preserved the graft for 28 days although there was histological evidence of mild rejection in some of the animals studied. Continuous CyA treatment preserved the graft for up to 56 days. The peripheral lymph nodes and spleens of untreated animals were transiently infiltrated by low numbers of donor cells that disappeared by day 6. There was a marked donor cell infiltration of the lymph nodes and spleens of 7 day. CyA-treated animals that was maintained during the administration of immunosuppressive therapy but that declined thereafter. Continuous CyA treatment sustained donor cell infiltration up to day 56. These findings suggest the presence of donor cells in recipient lymph nodes and spleen to be indicative of effective control of rejection and their disappearance to be predictive of developing rejection responses. Examination of recipient peripheral tissues for donor cells may provide an improved technique for monitoring clinical small bowel transplantation. PMID- 8447929 TI - Infections in human liver recipients: different patterns early and late after transplantation. AB - The first 49 consecutive patients who underwent orthotopic liver transplantation between 1984 and 1989 in our department were studied with regard to symptomatic and asymptomatic post-transplantation infections. The major infections carrying a risk of fatal outcome are presented. During the first 4 weeks, fungal and bacterial infections predominated, the percentages of patients affected being 27% and 35%, respectively. Eight patients (17%) suffered from bacterial septicemia, which in six cases was due to gram-negative micro-organisms. The bacterial septicemia was often associated with severe ischemic damage to the graft, rejection, or cholangitis. In addition, a concomitant invasive fungal infection supervened in seven out of eight septic patients, further aggravating the patients' condition. Seventeen of the 49 patients (35%) died after transplantation within 3.3 years. Infection was the cause of death in nine patients (18%), with bacterial septicemia and/or fungemia in eight of these. Cytomegalovirus (CMV) disease was the dominant cause of illness after the 1st month. While only 5 of the 49 patients developed CMV disease during the 1st month (10%), as many as 16 of the 40 recipients who survived beyond that time suffered from symptomatic CMV viremia (40%). CMV mismatching, i.e., the donation of a CMV positive organ to a CMV-seronegative recipient, entailed the highest risk for CMV disease. Pneumocystis carinii pneumonia occurred within 4 months in 10% of the patients. The four liver recipients affected were among the 20 patients not receiving trimethoprim-sulfamethoxazole prophylaxis. None of the 28 patients who received this prophylaxis over a 12-month period developed this complication (P < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447931 TI - Cyclosporin A-induced transient rise in plasma alkaline phosphatase in kidney transplant patients. AB - In 1981 cyclosporin A (CyA) became available and replaced azathioprine (Aza) as the immunosuppressive agent in kidney transplantation at the University Hospitals in Basel, Switzerland. Patients on CyA and prednisone (CyA/p) therapy frequently demonstrated an isolated rise in bone-derived serum alkaline phosphatase (aP) concentration, but patients on Aza and prednisone (Aza/p) therapy did not. On the basis of long-term aP concentration and using noninvasive means, the present retrospective study was designed to investigate biochemical markers and radiographic signs of bone disease after successful kidney transplantation in patients on Cya/p treatment. Similar investigations were performed in patients on Aza/p and the results were compared. Follow-up examinations included clinical examination, radiography of the hand, and biochemical analysis of serum and urine. In 139 renal transplant patients on CyA/p, aP increased transiently after successful grafting (at transplantation 84 +/- 43 U/l; on day 90, 112 +/- 82 U/l). In 50 patients aP levels were higher at the time of transplantation (120 +/ 80 U/l) and aP peaked after 8 +/- 6 months, at a mean concentration of 242 +/- 103 U/l. In these patients aP concentrations exceeded the normal range for 16 +/- 10 months. None of the patients on CyA/p showed symptoms of bone disease when aP was increased. Radiological surveys revealed more pronounced osteodystrophy in patients at the time of transplantation, which increased aP to above the normal range after transplantation. Despite this rise in aP, over the long term bone lesions improved radiographically while bone mass remained stable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447932 TI - Outsize peptides bulge out of the groove. AB - The highly polymorphic MHC class I molecules are a central part of the cellular immune response to viruses. They present peptides, processed from viral proteins synthesized in the cytosol, to CD8+ cytotoxic T cells (CTL) that eliminate virus infected cells. Here, Christopher Thorpe, describes the recent flurry of high resolution X-ray crystallographic structures that has allowed a general model of MHC-peptide interactions to be developed. PMID- 8447933 TI - Mixed haplotypes and autoimmunity. AB - Why do (NZB x NZW)F1 mice develop an autoimmune lupus-like syndrome? The second exons of the class II genes of NZB and NZW are identical to their counterparts of H-2d and H-2u haplotypes. Several lines of evidence suggest that this allows the production of a mixed haplotype molecule, I-E alpha dE beta z, and that this molecule plays a key role in the development of autoimmunity. PMID- 8447934 TI - The mechanisms of action of cyclosporin A in the treatment of psoriasis. AB - This article describes the effects of cyclosporin A (CsA) on the immunopathological mechanisms operative in psoriasis, a human skin disease. The main focus is the effect of CsA on keratinocytes, T cells and antigen-presenting cells, the key players in lesional psoriatic skin. The effect of CsA on other cells, such as neutrophils and endothelial cells, which are important in the maintenance of psoriasis, are also discussed. PMID- 8447935 TI - The skin immune system: progress in cutaneous biology. AB - The skin is an active, and in many ways unique, immunological microenvironment quite different from the other primary interfaces between the body and the environment (namely the mucosae). Here Jan D. Bos and Martien L. Kapsenberg identify the components of the skin immune system and describe the inflammatory and immunological responses that they can mount. New findings with regard to the immunophysiology and physiopathology of the human integument are emphasized. PMID- 8447936 TI - B-cell lineages exist in the mouse. PMID- 8447937 TI - The echinoid immune system revisited. PMID- 8447938 TI - The echinoid immune system revisited. PMID- 8447939 TI - The echinoid immune system revisited. PMID- 8447940 TI - [Seasonal variations in estrus behavior and ovulatory activity in Chios and Serres ewes in Greece]. AB - Sheep are seasonal breeders, but a lower seasonality has been reported for sheep breeds from the Mediterranean countries enabling spring matings. To further substantiate this, the present study compared seasonal variation in oestrus behaviour and ovulation in two Greek breeds (Chios and Serres) maintained in the same environment. In 27 adult ewes of each breed, oestrus behaviour, the occurrence of ovulation and ovulation rate were monitored during 2 successive years by daily inspection by rams, weekly progesterone assay in circulating blood plasma and monthly ovarian laparoscopy. The periods of anoestrus (109 +/- 8 (wk) vs 178 +/- 5 d) and anovulation (63 +/- 8 vs 149 +/- 6 d) were significantly shorter (P < 0.001 and P < 0.001) and more variable in Chios than in Serres ewes. Furthermore, the percentage of ewes exhibiting oestrus at least once monthly was significantly higher from March to July in Chios than in Serres ewes. Continuous ovulation throughout the year was noted in 5 and 2 Chios ewes during year 1 and 2, respectively. Ovulation rate (3.25 +/- 0.15 vs 1.45 +/- 0.04) was higher in Chios than in Serres ewes (P < 0.001) while duration of oestrus was also longer in Chios ewes (1.8 +/- 0.05 vs 1.5 +/- 0.06 d; P = 0.002). There were significant correlations between the duration of anovulatory periods of the 2 successive years in Chios (r = 0.43) but not Serres ewes. Ovulation rate was positively related to the onset of the sexual season in Serres but not in Chios ewes. The present data suggest that: i) the efficiency of Serres but not in Chios ewes. The present data suggest that: i) the efficiency of spring mating in these breeds is suboptimal since it is a period when the percentage of ewes exhibiting oestrus and ovulation as well as ovulation rate are limited, ii) owing to the large variation in seasonality within Chios ewes and to the good between year correlation in features of seasonality, selection against seasonality in Chios ewes could be worthwhile. PMID- 8447941 TI - Myosin expression in semitendinosus muscle during fetal development of cattle: immunocytochemical and electrophoretic analyses. AB - The pattern of expression of different types of myosin and the development of different muscle cell populations were studied in the semitendinosus muscle of cattle from 39 d of gestation to 30 d of post-natal life. Monoclonal antibodies specific to different myosin heavy chains were used. Two cell generations were identified during myogenesis. They appeared successively and were characterized by different patterns of expression of myosins. The first population, which was present from the first stage studied (39 d of gestation), gave rise to type I fibers, which, in the mature animal, express only slow myosin. A second generation became differentiated at about 120 d of fetal life and then developed into type II fibers (IIa, IIb or IIc). The beginning of differentiation was characterized in all the cell populations by the expression of specific types of embryonic or fetal myosins. A comparison of these results with findings from previous works shows a marked similarity between species in the pattern of myogenesis but great differences in the length of the different stages of development. In this respect, myogenesis in cattle closely resembles that in man. PMID- 8447942 TI - Effect of a viable yeast culture on digestibility and rumen fermentation in sheep fed different types of diets. AB - Five mature wethers fitted with rumen fistulas were fed grass hay and a sugarbeet pulp-based concentrate or maize silage and a cereal-based concentrate (50/50 digestible organic matter basis), or without with 5 g yeast supplement (Saccharomyces cerevisiae, Biosaf) per day in a latin square design. Diets were given for a 28-d adaptation period, followed by a 10-d collection period to determine digestibility and nitrogen retention data. Afterwards, rumen samples were taken on 3 consecutive days and analysed for volatile fatty acids, pH and ammonia. Digestibility and nitrogen balance were not affected by yeast treatment. Supplementation of yeast increased acetate: propionate ratio, butyrate, isoacids, pH and ammonia. The effects were more pronounced for the maize silage diet. These results demonstrate that the effect of yeast culture on rumen fermentation may depend on the nature of the diet. Living yeast cell number in the rumen fluid rapidly declined when dietary yeast was ceased. Furthermore, yeast cells survived the passage through the digestive tract. PMID- 8447943 TI - Effects of strain and embryo transfer model (embryos from one versus two donor does/recipient) on results of cryopreservation in rabbit. AB - Differential effects of 2 transfer models for normal thawed embryos of 1 donor doe were studied on the offspring rate and their embryo survival at birth from 3 selected rabbit strains (SY and SB: synthetic strains, NZ: New Zealand White). Morulae were obtained 64-66 h post-coitum from 93 adult does treated with 25 IU of hCG (SY:36, NZ:27, SB:30). Morphologically normal morulae were frozen in the presence of 1.5M DMSO and stored in liquid nitrogen. Normal thawed embryos were transferred into the oviducts of synchronized recipient does of the same strain 48 h after being injected with 25 IU of hCG (SY:28, NZ:21, SB:24). Each recipient received embryos from 1 (single transfer) or 2 different donor does (double transfer). Significant differences were observed in the post-thawing percentage of normal embryos between strains (SY:95 +/- 1% and SB:85 +/- 3%, P < 0.05; NZ: ,91 +/- 2%). After transfer, no significant differences were observed in pregnancy rate and offspring rate between the transfer models, whereas significant differences were only found in survival rate when all transfers were analyzed (double: 24 +/- 4% vs single: 14 +/- 3%, P < 0.05). An effect of strain was detected in the pregnancy rate (NZ: 33% vs SB: 71%, P < 0.05; SY: 61%) and in the survival rate per donor doe on pregnant recipient doe (SY: 42 +/- 5 vs SB: 19 +/- 5, P < 0.05; NZ: 34 +/- 7%). These results suggest a differential embryo sensitivity with respect to their genetic origin in both the freezing-thawing and transfer procedures. PMID- 8447945 TI - Proliferation of follicular cells and the effect of FSH on the onset of follicular growth in the ovary of 30-day old rabbits studied by continuous labelling with 3H-thymidine. AB - The ovary of the 30-d-old rabbit contains only small follicles with, at most, 3 or 4 layers of cells. We have estimated the labelling index of the follicular cells only from follicles having at least one labelled cell and using a zero truncated binomial distribution. The labelling index of the follicular cells of such follicles was weak and enlarged with the number of cells. It never exceeded 20%. Repeated injections of tritiated thymidine up to 8 times entailed a significant increase of the labelling index even for the smallest follicles. The labelling index of follicles was significantly increased 30 h after 1 injection of FSH (2 mg P-FSH). These results confirmed that the fraction of follicular cells that proliferate was low in the young rabbit ovary and the doubling time of the cells was large and that at this age, FSH increased the proliferation of cells. PMID- 8447944 TI - Spectrin and ankyrin like proteins in spermatids and spermatozoa of the hamster and some other mammals. AB - The presence of spectrin and ankyrin-like proteins was investigated during the differentiation and maturation of spermatozoa in mammalian species which have previously been studied for actin and calmodulin. These actin-binding proteins were characterized by immunoblotting and localized by immunoelectron microscopy. Neither spectrin nor ankyrin could be detected in the F-actin rich subacrosomal layer of spermatids in any species. In hamster and mouse maturing spermatids and spermatozoa, spectrin was mainly evidenced around the fibrous sheath of the flagellum whereas ankyrin was detected only in the neck. In rabbit spermatozoa, spectrin was evidenced in the outermost cytoplasmic layer of the post-acrosomal region and a light ankyrin labeling appeared in the neck. In rat, monkey and human sperm cells, these 2 proteins were not demonstrated. These results showed that as for actin there was no uniform pattern of distribution of spectrin and ankyrin among the 6 species studied. PMID- 8447946 TI - Limiting effects of uterine crowding on the number and weight of live pups at birth in hemiovariectomized and normal rabbit does. AB - Variation in the number, total weight, mean individual weight and minimum individual weight of live pups at first and second litter were studied in hemiovariectomized (H = 54 does) and normal (N = 55 does) rabbit does. The total number of implanted embryos in 25 unoperated (N) and 54 hemiovariectomized (H) does were recorded by laparoscopy on the 12th day of their second pregnancy. The total number of implanted embryos was not statistically different between experimental groups (m +/- SEM; H: 11.0 +/- 0.4; N: 12.4 +/- 0.5; P = 0.06). The number of total pups at birth (H: 7.7 +/- 0.2 vs N: 9.8 +/- 0.2; P < 0.01) was affected by hemiovariectomy even when analyzed as a constant total number of implanted embryos. The number of live pups (H: 7.0 +/- 0.2 vs N: 9.0 +/- 0.3; P < 0.01), the total weight of live pups (H: 395 +/- 11 g vs N: 479 +/- 12 g; P < 0.01), the mean litter weight (H: 58.9 +/- 1.1 g vs N: 54.1 +/- 0.7 g; P < 0.01) and the minimum individual weight of live pups at birth (H: 46.5 +/- 1.4 g vs N: 42.1 +/- 1.0 g; P < 0.05) were also affected by hemiovariectomy. The significance of hemiovariectomy effect disappeared when analyzed as a constant total number of pups at birth. A positive non-linear relationship between the total number of pups at birth and the total weight of live pups was detected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447947 TI - A simple system for nutritional studies with chronic consumption of liquid diet in rats. AB - A feeding system allowing liquid diet distribution to rats without any loss by evaporation is described. A liquid diet stirred continuously is offered to rats in water bottles. The diet is made available to the animals without any clotting throughout the 24-h period. Such a system could be applied to alcohol administration. PMID- 8447948 TI - Prepulse inhibition of acoustic startle in rats after lesions of the pedunculopontine tegmental nucleus. AB - Prepulse inhibition (PPI) of startle is impaired in schizophrenics, which suggests they have disturbances in circuitry that controls PPI. How activity in forebrain circuitry is communicated to the primary startle circuit to modulate PPI was explored. Subpallidal cells innervate the pedunculopontine tegmental nucleus (PPTg). Infusion of the gamma-aminobutyric acid antagonist picrotoxin into the subpallidum impaired PPI. In other rats, electrolytic PPTg lesions decreased or eliminated PPI, potentiated startle amplitude, and did not alter habituation. The disruption of PPI correlated significantly with the extent of PPTg damage. PPTg lesions reduced PPI when startle stimuli were weak or intense (104 or 120 dB) and when prepulse stimuli ranged from 2 to 17 dB above background but were most profound with prepulses 5-8 dB above background. The PPTg modulates sensorimotor gating and may process and transmit information from forebrain structures to the primary startle circuit. PMID- 8447949 TI - Taste reactivity responses elicited by cocaine-, phencyclidine-, and methamphetamine-paired sucrose solutions. AB - The nature of flavor-drug associations produced by a range of doses of the reinforcing agents cocaine (5, 10, 15, 20, or 40 mg/kg sc), phencyclidine (0.5, 2, 10, or 20 mg/kg sc), and methamphetamine (2, 5, or 10 mg/kg ip) were assessed by the taste reactivity (TR) test and the conditioned taste avoidance (CTA) test. Even at the highest doses tested, none of the agents produced aversive TR responding. At doses that produced equivalent-strength CTA, lithium did establish aversive TR responding. These results provide evidence that drugs that serve as reinforcers in other paradigms produce conditioned flavor avoidance that is not motivated by a conditioned dislike for the flavor. PMID- 8447951 TI - Lateralization of a sexually dimorphic brain area associated with steroid sensitive behavior in the male gerbil. AB - Emission rates of an androgen-sensitive male courtship vocalization were positively correlated with the volume of only the left hypothalamic sexually dimorphic area, pars compacta (SDApc) nucleus in sexually active male Mongolian gerbils. The asymmetric relationship between brain nucleus and vocal behavior was confirmed in testosterone (T)-treated castrated adult males but was eliminated by castration of males and did not exist in T-treated ovariectomized adult females. Interdependence between the left SDApc volume and emission rate was specific because no significant correlations were found between (a) nonvocal precopulatory or copulatory behaviors and left or right SDApc volumes and (b) a second sexually dimorphic brain area, the suprachiasmatic nucleus and vocal or other behavioral components. The asymmetric brain-behavior relationship depends on T effects in adult males and may be lateralized by perinatal T exposure. PMID- 8447950 TI - Peripeduncular nucleus lesions in the rat: I. Effects on maternal aggression, lactation, and maternal behavior during pre- and postpartum periods. AB - Bilateral peripeduncular (PPN) lesions made on the seventh postpartum day (L7) with either radiofrequency (RF) current or N-methyl-d,l-aspartic acid (NMDA)/phosphate buffered saline (PBS) reduced maternal aggression (MA) and partially inhibited lactation without producing significant deficits in other items of maternal behavior (MB). RF-PPN lesions did not interfere with prolactin secretion, which suggests that there was deficient oxytocinergic activity. The deficit in MA was not due to interruption of afferent suckling input to the PPN: either thelectomizing females (day L6) or producing bilateral knifecuts in the mesencephalon (placed caudal to the level of the PPN; Day L7) had no effect on MA, but both procedures impaired lactation. Deficits in MA produced by RF-PPN lesions developed gradually between Days L4 and L7; lesions made either prepartum or on Day L1 did not impair MA or MB. Deficits in lactation first appeared after RF-PPN lesions on Day L1. PMID- 8447952 TI - A neuroanatomical correlate of paternal and maternal behavior in the biparental California mouse (Peromyscus californicus). AB - The medial preoptic area (MPOA) is important in the control of maternal behavior in rodents, and it is sexually dimorphic. This study demonstrates that the MPOA of nonparental virgin male Peromyscus californicus (n = 10) is larger than that of virgin females (n = 9) because of a significantly greater number of neurons in the MPOA of virgin males. However, this sex difference in MPOA volume disappeared when males and females became parents. Soma size increased significantly when females became mothers. These data suggest that maternal behavior may require a structural change in the MPOA, whereas paternal responsivity, which is normally inhibited in virgin males, may require a change in neuronal activity. Furthermore, these results underscore the importance of reproductive status in examination of sexually dimorphic nuclear structures. PMID- 8447953 TI - Age-related deficits in brain estrogen receptors and sexual behavior of male rats. AB - Neural estrogen receptors (ER), serum testosterone (T), estradiol (E2) and luteinizing hormone (LH), and masculine sexual behavior were measured in young (5 months) and old (24 1/2 months) Fischer 344 male rats. We found that old intact males, which displayed significantly lower levels of sexual behavior, T, and LH than young intact males, also had lower levels of nuclear ER (ERn) in the amygdala (AMG). The age difference in ER binding did not appear to be a consequence of altered blood E2 levels because circulating E2 did not differ between the two age groups. Gonadectomy eliminated ejaculatory behavior and significantly reduced ERn in young males. When we administered exogenous T to gonadectomized males in doses that approximated levels found in young intact males, we found that sexual performance of old males was stimulated to precastration levels but not to levels found in young males. Moreover, such treatment failed to increase ERn in the AMG of old males to the levels measured in the AMG of young males. These results suggest that there is an association between the inability of T to increase ERn concentration in the AMG and the deficits in sexual performance that are characteristic of old males. Thus, the capacity of neural tissue to bind estrogen, presumably derived from circulating T, may be a limiting factor in the determination of androgen responsiveness in aging males. PMID- 8447954 TI - Manual and hemispheric specialization in the manipulation of a joystick by baboons (Papio papio). AB - Manual performance asymmetries were examined in 8 baboons (Papio papio). Using a joystick, monkeys had to track and hit with a cursor a randomly moving target on a monitor. The left or right hand was tested first, depending on group assignment, followed by a transfer to the other hand. A transfer effect is reported for the total number of trials to criterion and total number of successful trials. No effect was found for response time. However, for both test and transfer, the group initially tested with the left hand exhibited more controlled movements as demonstrated by shorter cursor's paths. Overall, it appears that the spatial components of the task are more sensitive to laterality effects than response times or learning scores. PMID- 8447955 TI - Selective hippocampal lesions abolish the contextual specificity of latent inhibition and conditioning. AB - The contextual specificity of the conditioned response (CR) and latent inhibition (LI) was examined in rats with selective hippocampal lesions. Acquisition of the CR to a novel conditioned stimulus (CS) was equally rapid in control and hippocampal rats (Experiments 1 and 2), and CS preexposure disrupted acquisition, (i.e., produced LI) to an equal extent in both groups (Experiment 2). In control subjects, however, the CR established in one context transferred incompletely to a second context (Experiment 1), and LI was attenuated when CS preexposure and conditioning occurred in different contexts (Experiment 3). This context specificity of the CR and LI was not apparent in hippocampal rats--the CR and LI transferred readily from one context to another. In addition, hippocampal rats were impaired in a spatial learning task (Experiment 2) but were unimpaired in learning a Pavlovian contextual discrimination (Experiment 3). These results suggest that a common contextual retrieval process underlies the contextual dependence of the CR and of LI and that this process is mediated by the hippocampus. PMID- 8447956 TI - A triple dissociation of memory systems: hippocampus, amygdala, and dorsal striatum. AB - This study investigated the respective roles of the hippocampus, the amygdala, and the dorsal striatum in learning and memory. A standard set of experimental conditions for studying the effects of lesions to the three brain areas using an 8-arm radial maze was used: a win-shift version, a conditioned cue preference (CCP) version, and a win-stay version. Damage to the hippocampal system impaired acquisition of the win-shift task but not the CCP or win-stay tasks. Damage to the lateral amygdala impaired acquisition of the CCP task but not the win-shift or win-stay tasks. Damage to the dorsal striatum impaired acquisition of the win stay task but not the win-shift or CCP tasks. These results are consistent with the hypothesis that the mammalian brain may be capable of acquiring different kinds of information with different, more-or-less independent neural systems. A neural system that includes the hippocampus may acquire information about the relationships among stimuli and events. A neural system that includes the amygdala may mediate the rapid acquisition of behaviors based on biologically significant events with affective properties. A neural system that includes the dorsal striatum may mediate the formation of reinforced stimulus-response associations. PMID- 8447957 TI - Impaired object recognition memory in rats following ischemia-induced damage to the hippocampus. AB - Transient cerebral ischemia can produce irreversible neuronal damage and permanent learning and memory impairments in humans. This study examined whether ischemia-induced brain damage in rats results in impairments on the delayed nonmatching-to-sample (DNMS) task, a nonspatial recognition task analogous to tests on which amnesic patients display impairments. Male Wistar rats received either sham surgery or 20-min forebrain ischemia induced by bilateral carotid occlusion and hypotension. Four weeks after surgery, ischemic rats were significantly impaired in both learning and performing the DNMS task at retention intervals up to 5 min. Extensive presurgical training did not reduce this impairment. Observable cell loss in ischemic rats was limited to CA1 pyramidal neurons and a subset of cells in the dentate gyrus. The results indicate that ischemic damage to the hippocampus in rats results in recognition memory deficits similar to those produced by ischemic damage in humans. PMID- 8447958 TI - Delay classical conditioning in young and older rabbits: initial acquisition and retention at 12 and 18 months. AB - Classical conditioning of the nictitating membrane-eyeblink response in young (7 months old) and older (36 months old) New Zealand white rabbits in a delay paradigm with a 400-ms conditioned stimulus-unconditioned stimulus interval was examined for initial acquisition and retention. Older animals required significantly more acquisition trials to reach learning criterion. Age differences in acquisition were temporary. Older rabbits responded at a level comparable to that of young rabbits such that total performance over the 630 trials of acquisition was not different. Rabbits in the explicitly unpaired control groups exhibited no age differences in unconditioned response amplitude or latency measures. Twelve- and 18-month retests demonstrated no significant age effects on retention. Patterns of retention differed between the age groups. Older rabbits required fewer trials to obtain the learning criterion at each phase of testing. Younger rabbits maintained a stable performance throughout training. PMID- 8447959 TI - Learning and memory of odor-reward association: selective impairment following horizontal diagonal band lesions. AB - Rats with horizontal diagonal band of Broca (HDBB) lesions were trained in a successive-cue olfactory discrimination using different intertrial intervals (ITIs). They learned the paradigm of the task, but substantial impairment in performance of odor-reward associations was observed when the ITIs were longer than 15 s. They performed as well as control animals with short ITIs when they were trained previously with long ITIs, but forgetting appeared very soon thereafter (24 hr later). The finding is that the HDBB is an essential relay between the hippocampal system and the olfactory cortex: The HDBB allows associative memory storage when a limited-duration short-memory system located elsewhere is overloaded. PMID- 8447960 TI - Receptive field plasticity in the auditory cortex during frequency discrimination training: selective retuning independent of task difficulty. AB - Classical conditioning is known to induce frequency-specific receptive field (RF) plasticity in the auditory cortex (ACx). This study determined the effects of discrimination training on RFs at two levels of task difficulty. Single unit and cluster discharges were recorded in the ACx of adult guinea pigs trained in a tone-shock frequency discrimination paradigm (30 intermixed trials each of positive conditioned stimulus [CS+]-shock and negative CS [CS-] alone) with behavioral performance indexed by the cardiac deceleration conditioned response (CR). After training in an easy task in which subjects developed discriminative CRs, they were trained in a difficult task (reduced frequency distance between CS+ and CS-) in which they failed to discriminate. However, frequency-specific RF plasticity developed at both levels of task difficulty. Responses to the frequency of the CS+ were increased, whereas responses to other frequencies, including the CS- and the prepotent best frequency (BF) were reduced. In many cases, tuning was shifted such that the frequency of the CS+ became the new BF. The effects were present or stronger after a 1-hr retention interval. The role of RF plasticity in the ACx is discussed for behavioral performance and information storage. PMID- 8447961 TI - Alcohol effects on TRH-induced prolactin response in lactating rats: in vivo and in vitro studies. AB - The site of action of alcohol in inhibiting suckling-induced prolactin release in lactating rats was examined by in vivo and in vitro studies. In vivo, sulpiride- and thyrotropin-releasing hormone (TRH)-induced prolactin release was studied in lactating rats separated from their litter. On day 7, dams were implanted with an atrial catheter. On day 10, pups were removed from dams at 0800 h and, after 5 h, an extension was attached to the catheter. An hour later, a baseline blood sample was removed and was followed by sulpiride (40 micrograms/kg) administration. Additional blood samples were withdrawn over 1 h. After the 60-min sample, sulpiride-administered rats were infused with 0.0, 1.0, or 2.0 g/kg b.wt. alcohol. Following alcohol, a postinfusion blood sample was removed, TRH (4.0 micrograms/kg) was administered, and subsequent blood samples were obtained 5, 10, 20, and 30 min after TRH. For in vitro studies, cells from lactating rats in midlactation were enzymatically dissociated, plated, and on culture day 5 were exposed to 0 or 10 nM TRH. Each set of cells were additionally exposed to 0, 100, or 300 mg% alcohol and media harvested after 4 h. In a subsequent study, plated cells were exposed to increasing doses of TRH in the presence of 0, 100, or 300 mg% alcohol and media harvested as above. Prolactin in plasma (in vivo studies) and medium (in vitro studies) was measured by RIA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447962 TI - Temperature in mice after ethanol: effect of probing and regain of righting reflex. AB - The handling involved in rectally probing a mouse in order to measure body temperature is a stress which results in an increase in body temperature. However, after an injection of ethanol the fall in body temperature caused by ethanol is exacerbated by probing. In mice, decreases in temperature following probing are ethanol-dose dependent and can be generated on both the falling and rising phases of the ethanol induced change in temperature. The effect of probing can be observed when the mice are under the hypnotic influence of ethanol, and regain of righting reflex itself is followed by a fall in temperature. The resumption of motor activity in undisturbed mice following an hypnotic dose of ethanol also is accompanied by a fall in temperature. Therefore, the drop in temperature observed in any of these procedures which involve moving the mice may be attributable to the disruption of heat conservation rather than a stress interaction. PMID- 8447963 TI - Ethanol relaxes pulmonary artery by release of prostaglandin and nitric oxide. AB - Acute-intake of ethanol is associated with vasodilation of vascular smooth muscle (VSM). Relaxation of VSM is dependent, in part, on the actions of nitric oxide (NO) and prostaglandin (PG) produced by endothelial cells (EC) lining the VSM. We examined the effects of endothelium rubbing and inhibition of EC synthesis of NO and PG on ethanol-induced relaxation of bovine pulmonary artery (BPA) and pulmonary vein (BPV) in vitro. Rings of isolated BPA and BPV were mounted in muscle chambers for the isometric recording of force development. Blood vessels were precontracted with an EC50 concentration of the thromboxane receptor mimetic U46619. Ethanol (0.01, 0.02, 0.04, 0.08, 0.16, 0.32, 0.64, and 1.28% (w/v) produced concentration-dependent relaxation of BPA and BPV. Ethanol-induced relaxation was attenuated in BPA with rubbed EC and by the NO synthase inhibitors, L-NG monomethylarginine (LNMMA, 50 microM) and L-nitroarginine (NOLA, 10 microM), and the prostaglandin cyclooxygenase inhibitor, ibuprofen (10 microM). In contrast, ethanol-induced relaxation of BPV was not affected by endothelium rubbing or by NOLA or LNMMA, but was partially attenuated by ibuprofen. Nitric oxide was measured with the chemiluminescence technique. Ethanol increased the content of NO released under basal conditions by the BPA but did not effect basal NO release from BPV. However, ethanol enhanced bradykinin-induced release of NO from BPA and BPV and, at low concentrations, augmented bradykinin-induced relaxation of both BPA and BPV.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8447964 TI - Effective stabilization of ethanol levels in multiple-well tissue culture plates. AB - Underestimation of ethanol (EtOH) volatility in vitro is a potential source of experimental error. EtOH (0-5% in culture medium) was added to 24- or 96-well tissue culture plates with standard low evaporation lids and incubated at 37 degrees C in humidified 7.5% CO2 and 92.5% air. After 72 hours, approximately 70% of the initial EtOH had disappeared from the aqueous phase of the plate (EtOH volatilization). EtOH concentrations gradually decreased in high-concentration wells (1-5%) and increased in low-concentration wells (0-0.1%) over time. This temporal redistribution of EtOH (EtOH diffusion) was detected after only 1 hour of incubation. Parafilm, Blenderm surgical tape, and ELISA plate-sealing tape barriers inconsistently or inadequately prevented EtOH volatilization and diffusion, but a newly designed plate-sealing clamp (PSC) apparatus inhibited this phenomenon. Rat hepatic sinusoidal endothelial cells cultured with the PSC apparatus maintained intact cell membranes for 72 hours and stable levels of monolayer permeability for at least 48 hours. By stabilizing in vitro EtOH concentrations, the PSC apparatus eliminates a potential source of major experimental error. PMID- 8447965 TI - Do rat strain differences in ethanol consumption reflect differences in ethanol sensitivity or the preparedness to learn? AB - Three strains of rats (Wistar, Sprague-Dawley, Long-Evans; n = 10/strain) were trained to drink various concentrations of ethanol (ETOH) in the rats' home cage in daily 30-min drinking sessions using a modified "Samson" sucrose-fading procedure. Wistar and Sprague-Dawley rats were similar in their voluntary intake of a wide range of ETOH concentrations and both of these strains drank considerably more ETOH than the Long-Evans strain. For comparison purposes only, pharmacological pretreatment tests were later conducted with the Sprague-Dawley strain of rats using a maintenance concentration of 20% w/v ETOH. Low-dose ETOH pretreatments increased (125% of control), and high-dose ETOH pretreatments decreased the subsequent voluntary consumption of ETOH. Low-dose nicotine pretreatments increased ETOH consumption to 148% of control intake, and high doses of nicotine decreased ETOH consumption. Both opiate antagonists, naloxone and naltrexone, produced dose-dependent decreases in ETOH consumption. The dopamine antagonist, haloperidol, produced dose- and time-dependent increases in voluntary ETOH consumption. The strain differences in voluntary ETOH consumption described in the present study differ from those previously described by other labs. We suggest that this strain-dependent disparity between laboratories, with respect to ETOH consumption/preference tasks, may reflect genetic differences in the preparedness to condition (learn) voluntary ETOH consumption rather than genetic differences in ETOH's reward/reinforcement attributes. PMID- 8447966 TI - Effects of chronic ethanol intake at a low dose on the rat brain dopaminergic system. AB - The effects of 8-week ethanol treatment (3% v/v in drinking water) on the rat brain dopaminergic system were investigated. Chronic ethanol consumption induced a significant increase in the number of dopamine D1 receptor sites in the caudate putamen. Conversely, no significant changes were observed in D2 receptor density or affinity. Biochemical results were in agreement with behavioral data, as amphetamine-induced locomotor hyperactivity was significantly higher in ethanol treated rats in comparison to controls. Moreover, grooming behavior in response to SKF 38393, a selective agonist of D1 receptors was potentiated in ethanol treated rats, whereas locomotor hyperactivity induced by LY 171555 (a selective agonist of D2 receptors) was not affected by ethanol treatment. The results indicate that changes in dopamine receptors may occur in the central nervous system at levels of ethanol intake that do not induce tolerance or dependence. PMID- 8447967 TI - The behavioral teratogenicity of alcohol is not affected by pretreatment with aspirin. AB - Prenatal alcohol exposure is associated with a variety of developmental abnormalities, including neuroanatomical, physical, and behavioral features. Several mechanisms for alcohol's teratogenic effects have been proposed. This study addresses the role of prostaglandins in the abnormal development that often occurs after maternal alcohol consumption. On gestation days 8 to 18, pregnant Sprague-Dawley rats were prenatally treated with 6 g/kg alcohol following pretreatment with 150 mg/kg aspirin. Behavioral testing of offspring included measures of open-field activity, exploratory behavior, passive avoidance, active avoidance, and acoustic startle response. In most cases, pretreatment with aspirin did not affect performance in alcohol-exposed or control rats. PMID- 8447968 TI - P3 in young boys as a predictor of adolescent substance use. AB - Event-related potentials were recorded during a visual, continuous performance task from 36 boys before use of alcohol or other drugs began. The boys were sons of 13 recovering alcoholics who themselves had a family history of alcoholism, 11 nonalcoholics with a family history of alcoholism, and 12 nonalcoholics with no family history of alcoholism. Four years after electrophysiological assessment, a behavioral questionnaire was administered (mean age = 16.1 years). A Substance Use score was derived from reported use of alcohol and other drugs, and from highly correlated delinquent behavior scores. P3s of lowest amplitude were associated with the highest adolescent Substance Use. The combination of reduced amplitude and prolonged latency of both target and nontarget P3 significantly predicted adolescent Substance Use scores after correction for subjects' age. Although this is the first electrophysiological predictor of adolescent substance use we are aware of, the effect was small, indicating the utility of P3 as a vulnerability marker for substance abuse disorders is likely to depend on its joint use with other measures. PMID- 8447970 TI - Effects of ethanol exposure on neuropeptide-stimulated calcium mobilization in N1E-115 neuroblastoma. AB - The effects of acute and chronic (100 mM for 7 days) ethanol exposures on resting intracellular free calcium, [Ca2+]i as well as bradykinin and neurotensin mediated [Ca2+]i mobilization were determined in intact N1E-115 neuroblastoma. [Ca2+]i was monitored fluorometrically with the calcium indicator, fluo-3/AM. Acute exposure to ethanol resulted in an inhibition of bradykinin mediated [Ca2+]i mobilization with significant effects observed only at 400 mM ethanol. Neurotensin mediated [Ca2+]i mobilization was not significantly affected by any of the ethanol concentrations tested. Similarly, resting [Ca2+]i (64 +/- 2 nM) was unaffected by either chronic or acute ethanol as high as 400 mM. However, chronic exposure to ethanol significantly reduced the magnitude of bradykinin mediated [Ca2+]i mobilization both in the absence and presence of extracellular [Ca2+]. In contrast, [Ca2+]i mobilization in the presence of various concentrations of neurotensin was not significantly affected by chronic ethanol exposure. The results suggest that neuropeptide mediated [Ca2+]i mobilization is relatively insensitive to the acute presence of ethanol. In addition, chronic ethanol exposure appears to have selective effects on receptor mediated [Ca2+]i mobilization because this response to bradykinin, but not neurotensin, was significantly reduced in cells exposed to ethanol. The results also suggest that the reduction in bradykinin stimulated [Ca2+]i mobilization in chronically exposed cells is due in part to an inhibition of the release of intracellularly bound [Ca2+]. PMID- 8447969 TI - Ethanol discrimination in Fawn-Hooded rats is compromised when compared to other strains. AB - The drug discrimination paradigm was used to evaluate the behavioral differences in response to ethanol between three strains of rats, viz., Sprague-Dawley, N/Nih and Fawn-Hooded. This latter group is thought to have a genetically-transmitted diminished central serotonin function. Each group of rats was trained to discriminate between the stimulus properties of 600 mg/kg ethanol and its vehicle in a two-lever, food-motivated operant task. Results indicate that the Fawn Hooded rats required a significantly longer time and a higher ethanol dose to reach criterion discrimination performance. Furthermore, the ED50 value of the Fawn-Hooded rats, once trained, was higher than the Sprague-Dawley or N/Nih rats. The possibility that a reciprocal relationship exists between lowered central serotonin concentrations and higher alcohol consumption is suggested and the hypothesis that the diminished ability to recognize the interoceptive stimuli produced by ethanol may result in larger amounts of ethanol being consumed is offered. PMID- 8447971 TI - New dimensions in caring. PMID- 8447972 TI - Community care: meeting the drug delivery challenge. PMID- 8447973 TI - A case of false imprisonment. PMID- 8447974 TI - Caution: music at work. PMID- 8447975 TI - Concerted effort. PMID- 8447976 TI - Counselling for the carers. PMID- 8447977 TI - The memory lingers on. PMID- 8447978 TI - Influenza in old age. PMID- 8447980 TI - Action ahead. PMID- 8447979 TI - Healthy eating in later life. PMID- 8447981 TI - As I was saying... PMID- 8447982 TI - Wonderful Copenhagen. PMID- 8447983 TI - Structures of perfragilin A and B. AB - The two perfragilins both have a similar backbone (an isoquinolinetrione skeleton) but differ in their substitution pattern at C(6) and C(7); perfragilin A has a thiomethyl group at C(6) and amide group at C(7), whereas perfragilin B has a thiomethyl group at both these positions. The effects of these substituents are reflected in the bond distances and bond angles, particularly in the benzoquinone segments of the molecules. The amide group in perfragilin A leads to a resonance structure and a planar isoquinoline ring system [r.m.s. deviation 0.026 (2) A]. The presence of the two thiomethyl groups in perfragilin B causes the isoquinoline ring system to exhibit significant deviations from planarity [r.m.s. deviation 0.067 (1) A]. PMID- 8447984 TI - Structure of 1,8-bis(hydroxymethyl)naphthalene. AB - 1,8-Naphthalenedimethanol, C12H12O2, M(r) = 188.24, monoclinic, P2(1)/n, a = 8.549(4), b = 4.856(3), c = 22.604(4) A, beta = 94.24(3) degrees, V = 935.8(7) A 3, Z = 4, Dx = 1.34 g cm-3, lambda(Mo K alpha) = 0.71073 A, mu = 0.84 cm-1, F(000) = 400, T = 295 K, R = 0.042 for 1455 unique reflections having I > 3 sigma I. In the title structure the exterior angles at ring atoms C(1), C(8) and C(9) deviate significantly from 120 degrees as a result of the steric interactions of the hydroxymethyl substituents. The ten C atoms comprising the naphthalene core have an average deviation of 0.012 (7) A from the best least-squares plane describing the core. The conformation of the title compound is compared to those of other 1,8-disubstituted naphthalenes. Each hydroxy group is involved in hydrogen bonding as both acceptor and donor, creating infinite chains that propagate in the [010] directions. The neutron-adjusted parameters for the two H...O(acceptor) distances are 1.78 (3) and 1.80 (3) A and for the two O- H...O(acceptor) angles are 165 (2) and 170 (2) degrees. The packing arrangement can be described as a modified herringbone structure with the shortest crystallographic axis coinciding with the b axis of the standard monoclinic setting. PMID- 8447985 TI - Exact conditional distribution of a three-phase invariant in the space group P1. III. Construction of an improved Cochran-like approximation. AB - An exact representation of the accurately computable conditional probability density function (c.p.d.f.) of the three-phase invariant for the space group P1 was developed in paper I of this series [Shmueli, Rabinovich & Weiss (1989). Acta Cryst. A45, 361-367]. The computation of this function is too time-consuming for it to be of practical value. It is therefore desirable to find simple approximations based on the exact result that may be more accurate than the familiar Cochran approximation or its extensions. One such approximation, presented here, has the same functional form as the Cochran approximation but with a modified parameter in place of that appearing in Cochran's distribution. Some of the numerical procedures used in the estimation of this modified parameter are also discussed. PMID- 8447986 TI - The use of protein homologues in the rotation function. AB - The success of molecular replacement depends, in part, on the degree of similarity of the target and search molecules. We have systematically investigated this effect in cross-rotation functions for members of the aspartic proteinase family of enzymes. The influence of various parameters on peak heights was investigated for six search models using magnitude of F(obs) data for two target enzymes. The beneficial effects of high-resolution data and a large radius of integration are most pronounced when target and search molecules have high percentage identities. Correction for small differences in domain-domain orientation (typically 4-8 degrees) between search and target structures leads to only a marginal improvement in the rotation-function peak height. There is an almost linear relationship between the structural distance, D, a parameter used in cluster analysis to define differences between three-dimensional protein structures, and the height of the cross-rotation-function peaks. PMID- 8447987 TI - Nutritional assessment of the patient in the intensive care unit. AB - Early identification and treatment of malnutrition in hospitalized patients remain important aspects of care, especially in critically ill patients. Thorough knowledge of a patient's nutritional history, physical assessment and clinical laboratory findings are critical in order to accurately determine the degree of malnutrition, if present, as well as metabolic energy needs. The nurse plays a vital role in gathering this valuable clinical information. Although there is no single test to determine malnutrition, the utilization of a complete nutritional assessment is the best tool to properly identify and treat malnutrition. PMID- 8447988 TI - The immunologic role of the gastrointestinal tract. AB - During the past few decades, researchers have shed new light on the role of nutritional support in the immunocompromised critically ill patient. "Nutritional pharmacology" has become the catch phrase of the 1990s due to the impact of selected nutrients on host immune defenses. When feasible, enteral nutrition is preferred to parenteral nutrition to preserve the integrity of the gut mucosal barrier, especially when administered jejunally in the early stages of hypermetabolism. Glutamine and fiber provide necessary fuels for the gastrointestinal tract, whereas arginine and omega-3 fatty acids exert beneficial effects on certain cells of the immune system. Daly et al demonstrated that "enteral nutrition with supplemental arginine, RNA nucleotides and omega-3 fatty acids (Impact, Sandoz Nutrition, Minneapolis, MN) compared with a standard enteral diet, significantly improved immune, metabolic and clinical outcomes (22% mean reduction in length of stay) in UGI cancer patients undergoing surgery." Although more research is needed in the area of nutritional pharmacology, newly available nutrient-specific enteral products (Table 1) provide promise for altering the clinical outcome of immunocompromised patients. PMID- 8447989 TI - Gastrointestinal manifestations of HIV/AIDS. AB - HIV-infected patients are faced with a number of infections that affect every organ system. The gastrointestinal system is highly vulnerable to the many pathogens that are capable of invading the immunocompromised patient, thus creating some of the most frustrating problems for both the patient and the clinician. This article reviews the potential problems in the HIV-infected patient specific to the GI tract and discusses the current therapies available for these problems. PMID- 8447990 TI - Gastrointestinal trauma. AB - The incidence of gastrointestinal trauma is low in comparison with solid organ injury to the abdomen. The most commonly injured organs are the small bowel and colon. Knowledge of the mechanism of injury alerts the nurse to areas of potential injury and guides the clinical examination. Because of the delayed presentation of these injuries, the nurse must have a high degree of suspicion for the patient who presents with the following clinical findings: bruising of the abdomen, abdominal tenderness or guarding, leukocytosis and elevated amylase and lipase, absent or decreased bowel sounds, and abdominal distention. Morbidity and mortality are directly related to the failure to treat the injuries early and the number of associated injuries. Monitoring of the hemodynamic, respiratory, and metabolic status, along with fluid and electrolyte balance, are key in the management of patients. Surveillance for signs of infection is mandatory for preventing sepsis in these types of injuries. Maintenance of skin integrity is a major concern and requires vigilant nursing care and, in some instances, innovative ways to manage the drainage from wounds and drains. Continuous monitoring and surveillance of the patient with trauma to the gastrointestinal tract will alert the nurse to the injury and prevent complications. These include hemorrhage, abscess, fistula, peritonitis, pancreatitis, esophageal stricture, and wound problems. PMID- 8447991 TI - Fulminant hepatic failure. AB - Fulminant hepatic failure is a complex clinical syndrome that has a diverse etiology, an unpredictable course, and a high mortality rate. The acutely ill patient admitted to the ICU with this condition often presents a challenge to the intensive care staff because of the life-threatening, multi-system complications. This article presents a review of the etiology, complications, and management of fulminant hepatic failure. PMID- 8447992 TI - The adult with bleeding esophageal varices. AB - Bleeding esophageal varices are a life-threatening complication of portal hypertension. During the emergent phase, nurses have an important role in assessing the patient's response to volume replacement and in monitoring interventions to control hemorrhage. Complications contribute to the high mortality associated with variceal hemorrhage. Knowledge of the pharmacologic side effects of vasopressin and of the potential complications associated with endoscopic injection sclerotherapy and esophagogastric balloon tamponade is critical for successful nursing management of the adult with bleeding esophageal varices. The goal of long-term management is to prevent recurrent hemorrhage. This is accomplished by repeated injection sclerotherapy and strategies to reduce portal pressure. Patient education is focused on modification of behaviors that increase the risk for bleeding and on the early recognition of recurrent bleeding. PMID- 8447993 TI - Stress ulceration in the critically ill patient. AB - Even though considerable progress has been made in prophylaxis and treatment, the problem of stress ulceration continues to pose a serious threat to many critically ill patients. Intensive nursing assessments and interventions can dramatically affect outcomes for these patients. Critical care nurses must identify high-risk patients, carefully monitor their course, and collaborate with physicians, pharmacists, and other members of the health care team to select optimal therapies. PMID- 8447994 TI - Ethics and nutritional support in the intensive care unit. AB - Provision of nutrition and hydration through artificial means is an invasive medical intervention. As such, procedures for supplying nutrition and hydration impose burdens as well as provide benefits and may, under certain circumstances, be foregone. However, in the intensive care unit, the needs of most patients are best served by providing nutritional support. For many critically ill patients, the long-term prognosis and potential for response to treatment are uncertain. For these reasons, the presumption should be in favor of providing nutrition and hydration. PMID- 8447995 TI - Acute mesenteric ischemia. AB - Acute mesenteric ischemia is a potentially life-threatening vascular disorder affecting the gastrointestinal tract. The prognosis depends on early recognition, accurate diagnosis, and timely intervention to prevent extensive tissue necrosis and the onset of sepsis and multi-organ complications. Identifying the patient at risk, evaluating physical findings and laboratory data, maintaining adequate cardiac output and perfusion pressure, and implementing medical interventions are nursing care measures essential to patient survival. Future directions for the management of acute mesenteric ischemia are focused on identifying early markers of ischemia and mucosal injury to diagnose the condition accurately and reliably before the onset of systemic consequences. PMID- 8447996 TI - Esophagogastrectomy. AB - The diagnosis of esophageal cancer continues to stimulate much research to find the most effective methods of treatment. Combined radiotherapy and chemotherapy may produce results as good as if not better than those with operation plus radiotherapy and chemotherapy. Esophagogastrectomy is performed using any one of several surgical approaches. The individual status of the patient is an important determinant when selecting the surgical approach. There is no clear evidence that one approach is superior to another. Patients should be evaluated appropriately and prepared for operation so that they have the best chance for having a benign postoperative course. Postoperative nursing management requires complex assessment and intervention skills. The optimal approach to the management of esophageal cancer has yet to be defined. Esophagogastrectomy remains primarily a palliative, not curative, approach to patient management. The prevention of postoperative complications through astute assessment and intervention will improve the quality of patient outcomes. PMID- 8447997 TI - Acute pancreatitis. AB - The patient with acute pancreatitis requires constant assessments and interventions to minimize pancreatic inflammation and promote early detection and treatment of systemic complications. The onset of acute pancreatitis is most commonly initiated by biliary or alcohol disease, although many other causes have identified. The course of the disease may range from mild to fulminant based on the degree of pancreatic necrosis. Significant clinical symptoms include abdominal pain, nausea, and vomiting. The patient may present with signs of hypovolemic shock, with associated sequestration of fluid in the peritoneum as a result of inflammatory and mediated responses. Laboratory evidence of the disease includes increased levels of amylase and lipase, although a definitive diagnosis cannot be made without radiographic tests. Multisystem failure can occur in necrotizing acute pancreatitis as a result of mediators that are activated by the proteolytic enzymes, normally produced by the pancreas, and released into the peritoneum by injured cells. Collaborative management of the patient includes therapies directed at correcting initiating events, hemodynamic stabilization, and supportive measures to rest the pancreas and resolve presenting clinical symptoms. The management of multisystem organ failure that can result from necrotizing pancreatitis is a multidisciplinary challenge. PMID- 8447998 TI - Small intestine transplantation: a nursing perspective. AB - Intestinal transplantation has become a viable treatment modality for the patient with short gut syndrome. The potential for the development of serious postoperative complications contributes to the complexity of caring for these patients. Through astute observation, thorough assessment, and intelligent intervention, the nurse can directly affect the ultimate success of intestinal transplantation. A dedicated team approach, along with a sincere patient/family commitment, will help to provide for optimal patient management and a successful outcome. PMID- 8447999 TI - The significance of enteral nutrition in the intensive care unit patient. AB - The gut and its nonimmunologic and immunologic barriers have an important role in the survival of critically ill patients. Burns, hemorrhagic shock, intestinal obstruction, protein-calorie malnutrition, and several therapies (e.g., parenteral nutrition, steroids), used in critically ill patients are known to promote the breakdown of the mucosal barrier and to permit translocation of intestinal pathogens. Enteral nutrition, in conjunction with the use of certain immunostimulatory nutrients, can now be used to prevent or minimize damage to the mucosal barrier and to enhance its immunologic function in critically ill patients. PMID- 8448000 TI - Electrolyte and drug management in nutritional support. AB - Interventional nutritional support is a complex therapeutic entity. Metabolic complications associated with this therapy are numerous. It is imperative to monitor electrolytes very closely during parenteral and enteral nutritional support and to correct deficiencies or to compensate for increases in serum concentrations when appropriate. It is also critical to observe patients receiving drug therapy to avoid untoward drug-nutrient interactions and to be able to compensate for adverse metabolic effects of medications. To achieve successful nutritional support, careful monitoring of electrolytes and drugs is necessary. PMID- 8448001 TI - Nutritional support for the patient with pancreatobiliary disease. AB - Critically ill patients with severe pancreatobiliary disease exhibit multiple nutritional alterations compounded by the stress response. Acute pancreatitis may present as a life-threatening illness; patients are likely to be hypermetabolic and may have hyperglycemia and hypocalcemia. Nutritional support from parenteral or enteral feeding will probably be required in patients presenting with three or more positive risk factors as determined by Ranson criteria. Nutritional therapies for liver disease vary according to the specific disorder manifested. Patients with fulminant hepatic failure need to be monitored for profound hypoglycemia. Encephalopathy may develop in patients with acute-on-chronic liver disease, necessitating a protein restriction. Patients undergoing liver transplant are a perioperative challenge due to the combination of preoperative malnutrition, an extensive surgical procedure, and postoperative stress. Such patients require individualized assessment and management. PMID- 8448002 TI - Nutritional support for the patient with diabetes. AB - Nutritional support for critically ill patients with diabetes mellitus will be successful when nutrition meets the patient's metabolic needs; blood glucose levels are maintained between 100 and 200 mg/dL; complications of hyperglycemia, sepsis, and hypoglycemia are prevented; insulin dosages take basal metabolic needs, stress level, pharmacologic therapy, and the degree of illness into account; and nutritional support is provided in the least invasive manner possible. Providing nutritional support without adequate glycemic control and appropriate insulin administration is counterproductive for the patient. Careful monitoring of blood glucose and blood chemistries, along with the physical assessment of patients receiving nutritional support, are essential to successful treatment. Further research is necessary to define better which levels of glycemic control are most beneficial for providing optimal nutritional support for critically ill patients with diabetes mellitus. PMID- 8448003 TI - Nutritional support of the cardiopulmonary patient. AB - In this article, the consequences of malnutrition on the cardiopulmonary system are reviewed. Methods of identification of malnourished patients, means of calculating nutritional requirements, and procedures for providing adequate and safe nutritional repletion are discussed. Complications of nutrition support and methods to prevent such complications are reviewed. PMID- 8448004 TI - Nutritional support of the critically ill child. AB - There is a growing awareness that the nutrition an individual receives as a child may exert significant consequences later in life. The successful treatment of critically ill children influences their potential for full recovery and optimal outcome. This requires an understanding of how the child responds to stress and starvation. Daily energy needs of the child in the intensive care unit are highly variable. Specific knowledge of the nutritional assessment of these children, whether sustaining an acute or chronic illness, is required, as is an understanding of how the disease process affects the child. Further work needs to be done to evaluate how chronic illness affects the growth, development, and maturation of the child. Assessment parameters remain somewhat controversial, and recent studies indicate that, indeed, critically ill children may be overfed if standard equations are used to calculate needs. Poor clinical outcomes can occur if the child is underfed or overfed. The long-term results of specific diets, micronutrients, glutamine, and new access routes into the infant are not yet known. Research in these areas is rapidly growing, and the new knowledge will provide a greater ability to meet the individual needs of the critically ill child. Perhaps in the future the treatment of choice in patients with organ failure will involve specific micronutrients that influence the immune status and cellular degradation. In the meantime, critically ill children deserve to have their basic nutritional needs met, and nurses can do much to individualize the nutritional support required to produce optimal patient outcomes. PMID- 8448005 TI - Nutritional support for the patient with renal failure. AB - Renal failure presents patients and caregivers alike with numerous dilemmas in nutritional management. Too much protein, phosphate, or electrolytes, and the patient's renal failure becomes more symptomatic; too little of these nutrients and the patient is at great risk of developing fluid and electrolyte imbalances and of becoming protein-calorie malnourished. Dietary manipulation and often vigorous nutritional intervention (i.e., parenteral nutrition) are a must for these patients' survival. The nurse needs to understand the rationales behind nutritional care choices made by the physician and dietitian, and to be able to convey these rationales to the patient. The nurse also needs to be aware that the patient will use food, eating, and diet as a focus for acting out anxiety, fear, hopelessness, and anger. The nurse should also realize that these emotions are due, in part, to the metabolic derangements induced by the renal disease itself. PMID- 8448006 TI - Nutritional support in the hypermetabolic patient. AB - A patient who has experienced a major injury needs to undergo a careful assessment for hypermetabolism and malnutrition. Metabolic supportive therapy focuses on the support of the structural and functional integrity of organs and organ systems. The principles are derived from an understanding of the metabolic and physiologic responses to injury. When supportive therapy is applied in this manner, the chance of recovery can be significantly affected. PMID- 8448007 TI - Some aspects of the use of laser Doppler flow meters for recording tissue blood flow. AB - Laser Doppler flow meters are used to provide continuous records of blood flow in tissues. An account is given of their principles of operation and of the differences between two of the commercially available instruments: the Periflux model PF3 and the Moor blood flow monitor model MBF3D. The Periflux tended to have higher noise levels and to drift more than the Moor. The principal disadvantage of these instruments is that they cannot be calibrated in absolute units of blood flow. It is suggested that the method of standardization adopted for the Periflux be used with other machines, based on the signal produced by the Brownian motion of a 0.5% suspension of 0.48 micron diameter polystyrene microspheres at 20 degrees C. The signal representing zero flow in a tissue can be obtained by recording with the same light intensity from a stationary reflector. In model systems the instruments are linear with red cell volume fractions up to only 1%, which is below that likely to be encountered in many tissues. The effects of ambient light and the origin of movement artifacts are also considered. PMID- 8448008 TI - Localized neural control of blood flow in the posterior region of the knee joint in anaesthetized rabbits. AB - Radiolabelled microspheres were used to measure blood flow of structures in and around the rabbit knee joint and to determine the effect of electrical stimulation of the posterior articular nerve (PAN) supplying the knee. Surgical exposure of the posterior aspect of the knee joint 'capsule' and section of PAN resulted in an increase in flow restricted to this region. Electrical stimulation produced frequency-dependent reductions of blood flow in the posterior region, but no alterations occurred in the anterior region or in any other surrounding structures, suggesting that the neural supply is specific to the posterior joint capsule. PMID- 8448009 TI - Enterocytes on rat jejunal villi but not in the crypts posses m3 mRNA for the M3 muscarinic receptor localized by in situ hybridization. AB - Localization of m3 mRNA, for the expression of the M3 muscarinic receptor, along the crypt-villus axis, was undertaken in rat jejunum by in situ hybridization. While enterocytes on the lower two-thirds of the villi showed the presence of m3 mRNA it was absent in the crypt enterocytes. This indicates that the final locus of muscarinically activated jejunal secretion is mediated by the M3 receptor on the enterocytes of the villi and not via the crypt cells. PMID- 8448010 TI - The use of midbrain stimulation to identify the discharges of static and dynamic fusimotor neurones during reflex jaw movements in the anaesthetized cat. AB - In anaesthetized cats, it was possible to enhance the dynamic sensitivity to stretch of jaw muscle spindle primary afferents by electrical stimulation in the midbrain. This effect was taken to be due to excitation of dynamic fusimotor neurones and was used to identify fusimotor fibres as static or dynamic in recordings from the masseter nerve. During reflex movements, some fusimotor fibres fired tonically, while others were markedly modulated with increases in firing corresponding approximately to muscle shortening. The modulated group had a significantly higher mean resting firing frequency than the tonic group. Midbrain stimulation at points shown to produce dynamic effects on muscle spindle primary afferents increased the discharge frequency of the tonic fusimotor units, but did not significantly affect the modulated fusimotor units. We conclude that the fusimotor fibres in the masseter nerve which fire tonically during reflex jaw movements are probably of the dynamic type, while those which show strongly modulated increases in firing are probably static. PMID- 8448011 TI - Properties of diazoxide and cromakalim-induced activation of potassium channels in cultured rat and RINm5F insulin-secreting cells; effects of GTP. AB - Experiments have been carried out to examine the effects of GTP on the opening of K+ channels in insulin-secreting cells by diazoxide (0.2 mM) and cromakalim (0.5 mM). Using rat pancreatic beta-cells and RINm5F insulinoma cells, patch-clamp recordings of unitary ATP-sensitive potassium (K+ATP) channel currents were made in either the open cell or outside-out patch recording configurations. Adding diazoxide or cromakalim to either the inside or the outside face of the membrane was found regularly to cause the activation of K+ATP channels in the presence of 0.5 mM ATP. We now demonstrate that in the absence of ATP but in the presence of GTP (0.5-1 mM), both diazoxide and cromakalim activate channels. Effects are rapid in onset, sustained and readily reversible. Both the diazoxide- and cromakalim-induced activation of K+ATP channels were mediated by increases in channel open-state probability, and were not associated with any significant change in either channel amplitude or by an increase in the number of channels in the patch. The actions of both diazoxide and cromakalim were not affected by overnight pretreatment of cells with pertussis toxin, suggesting that PTX sensitive GTP-binding proteins are not involved in mediating the actions of either compound. These data indicate that diazoxide and cromakalim open K+ATP channels in a manner not solely dependent upon intracellular ATP, but by mechanisms involving other cytosolic nucleotides, including GTP. PMID- 8448012 TI - Neutral endopeptidase (EC 3.4.24.11) modulates the contractile effects of neuropeptides on muscle cells from the guinea-pig stomach. AB - The objectives of this investigation were to characterize neuropeptide-degrading enzymes on the surface of gastric muscle cells and to determine their physiological function. Neutral endopeptidase (NEP, EC 3.4.24.11) activity was measured using the fluorogenic substrate glutaryl-Ala-Ala-Phe-4-methoxy-2 naphthylamine. The NEP inhibitors phosphoramidon and DL-thiorphan (1 microM) inhibited degradation of the substrate by gastric muscle membranes by 100% and by freshly dispersed gastric muscle cells by 55-60%. The phosphoramidon or DL thiorphan-inhibitable activity, attributed to NEP, of membranes was 112 +/- 4.0 pmol h-1 (micrograms protein)-1 and of cells was 4.2 +/- 0.8 nmol h-1 (10(6) cells)-1. This activity was associated with membranes prepared from cells and was not detected in the cytoplasm or in the cell incubation solution. Gastric muscle membranes were fractionated by electrophoresis and analysed by Western blotting using two NEP antisera. Both antisera recognized a protein in membranes with an electrophoretic mobility identical to that of recombinant human NEP and an apparent molecular mass of approximately 95 kDa. Neuropeptides were degraded by membranes with specific activities in the order of [Leu5]enkephalin > [Met5]enkephalin > gastrin-releasing peptide-10 (GRP-10) > [D Ala2][Leu5]enkephalin > somatostatin-14. Phosphoramidon and DL-thiorphan similarly inhibited the degradation of GRP-10 (mean of 35% inhibition), somatostatin-14 (57%) and the aminopeptidase-resistant analogue, [D Ala2][Leu5]enkephalin (75%). When aminopeptidases were inhibited with amastatin (10 microM) phosphoramidon inhibited degradation of [Leu5]enkephalin (54%) and [Met5]enkephalin (100%). Phosphoramidon increased the potency of the contractile effects of neuropeptides on muscle cells by > 280-fold for somatostatin-14, 17 fold for GRP-10, 18-fold for [Met5]enkephalin and 14-fold for [Leu5]enkephalin. The results show that an NEP-like enzyme on the surface of gastric muscle cells degrades and inactivates enkephalins, GRP-10 and somatostatin-14 and acts in a manner analogous to that of acetylcholinesterase in the neuromuscular junction of skeletal muscle. PMID- 8448013 TI - The effects of increasing cell length on auxotonic contractions; membrane potential and intracellular calcium transients in single guinea-pig ventricular myocytes. AB - Until recently the investigation of length-dependent effects in cardiac muscle was restricted to multicellular preparations. We describe our experimental set-up which for the first time, in single cardiac myocytes, permits the effects of changes in cell length on auxotonic contractions (measured by carbon fibre transducers) to be simultaneously recorded with the effects on membrane potential and/or changes in intracellular calcium concentration (using indo-1 AM, acetoxylmethyl form). Consistent with previous findings (in experiments at 20-25 degrees C and 0.25 Hz) we report that following a stretch there was an increase in passive tension and contraction. A stretch which increased sarcomere length by approximately 3% had no significant effect on resting membrane potential or action potential amplitude. There was, however, a significant decrease in the action potential duration (P < 0.01, n = 8). No significant change in the amplitude of the intracellular calcium transient was seen following a stretch but a reduction in its duration was observed (P < 0.025, n = 11). Our observations on intracellular calcium transients are consistent with the hypothesis that, in mechanically loaded preparations, their time course is more dependent on changes in tension than changes in length. PMID- 8448014 TI - Basement membrane matrices in tissue development. PMID- 8448015 TI - Immunohistochemical localization of chondroitin sulfate, chondroitin sulfate proteoglycan, heparan sulfate proteoglycan, entactin, and laminin in basement membranes of postnatal developing and adult rat lungs. AB - Histologic preparations of lungs from 1-, 5-, 10-, 18-, and 25-day-old postnatal and adult rats were examined immunohistochemically with antibodies specific against chondroitin sulfate (CS), basement membrane chondroitin sulfate proteoglycan (BM-CSPG), heparan sulfate proteoglycan (HSPG), entactin, and laminin. A monoclonal antibody specific for the glycosaminoglycan portion (CS) of CSPG and a monoclonal antibody against the core protein of CSPG were used in an immunoperoxidase sequence to stain extracellular matrix (ECM) components of pulmonary basement membranes (BMs). Anti-CS stained airway BM strongly and alveolar BM weakly in the adult rat lung, as well as in vascular and airway adventitia. In developing lungs, immunoreactivity was strong in all ECM sites, including BM, at day 1 postnatal, and progressively diminished thereafter except in vascular and airway adventitia. Anti-CSPG stained alveolar, airway, and vascular BMs, in addition to smooth muscle external laminae (EL), in the adult and developing rat. Immunostaining for CSPG required hyaluronidase digestion, whereas CS staining was lost with the same treatment. A polyclonal antibody to the core protein of HSPG was found to be similarly distributed to CSPG by immunoperoxidase staining in adult and developing rat lungs, with the notable exception that little immunoreactivity for HSPG was found in smooth muscle EL. Commercially obtained polyclonal antibodies to entactin and laminin gave immunostaining comparable to that seen with CSPG, except that entactin showed particular affinity for EL. These results offer a more detailed perspective on previous survey observations of CSPG, HSPG, and entactin in the rat lung, and describe the immunoreactivity of CS for the first time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448017 TI - Human tracheal epithelial cells selectively incorporate 15 hydroxyeicosatetraenoic acid into phosphatidylinositol. AB - 15-hydroxyeicosatetraenoic acid (15-HETE) is the major lipoxygenase metabolite of arachidonic acid produced by human airway epithelial cells. Because HETEs have been shown to be rapidly metabolized and/or incorporated into cellular lipids in other cell types, we investigated the uptake, metabolism, and intracellular distribution of exogenous 15-HETE by primary monolayer cultures of human tracheal epithelial (HTE) cells. At concentrations of 0.1 microM, [3H]15-HETE was rapidly incorporated by HTE cells and also metabolized primarily by beta-oxidation to several more polar products that were released extracellularly. The majority of cell-associated [3H]15-HETE radiolabel was distributed into phospholipids, with phosphatidylinositol (PI) accounting for approximately 75% of phospholipid radiolabel. Exogenous 5- and 12-HETE were also metabolized by HTE cells but were less extensively incorporated into phospholipids and were distributed primarily into phosphatidylcholine and phosphatidylethanolamine. Phospholipase A2 hydrolysis indicated selective esterification of unmodified 15-HETE to the sn-2 position of phospholipids. 15-HETE incorporation into total phospholipids and into PI was saturable (half maximal incorporation at 0.82 and 0.68 microM, respectively), while incorporation into neutral lipids continued to increase at concentrations of 15-HETE up to 5 microM. The incorporation of 15-HETE into PI was metabolically stable, with an intracellular half-life of 12 h, and was not subject to mobilization in response to 5 microM calcium ionophore A23187. HTE cells can incorporate and metabolize HETEs that the cells themselves produce as well as those that might be released by inflammatory cells recruited into the airway.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448016 TI - Changes in levels of mRNA encoding myosin heavy chain in porcine trachealis during ontogenesis. AB - We determined the steady-state level of mRNA for myosin heavy chain (MHC) from airway smooth muscle during maturation in domestic swine. Tissues were excised, and airway smooth muscle was dissected from three neonatal (NEO), three 2-wk-old swine (2ws), three 10-wk-old swine (10ws), and three adult swine. Total RNA was isolated, fractionated, and transferred to a nitrocellulose membrane (Northern blot). A single-stranded oligonucleotide of 63-nt was synthesized corresponding to the 3' coding region of the chicken gizzard MHC cDNA. This region appeared to be highly conserved (92% nucleotide sequence homology with the corresponding portion of rabbit uterine smooth muscle MHC cDNA). Northern blots, which were loaded with equivalent quantities of total RNA, were probed with gamma 32P labeled synthetic oligonucleotide, and, under stringent washing conditions, the 5' end-labeled DNA was hybridized to a single band of the expected molecular weight. The mRNA for total myosin was quantified using autoradiograms of blots, and signal intensity was measured as integrated areas expressed as arbitrary densitometric units x mm (AU). The content of mRNA for MHC was substantially greater in NEO than in more mature animals; maximal area was 1.33 +/- 0.15 AU for NEO, 0.33 +/- 0.05 AU for 2ws, 0.30 +/- 0.04 AU for 10ws, and 0.34 +/- 0.08 AU for adult swine (P < 0.05, NEO versus 2ws, 10ws, and adult). Rehybridization of each blot with a 28S ribosomal RNA probe confirmed comparable total RNA loadings for all tissue samples.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448018 TI - Production of eicosanoids in response to endothelin-1 and identification of specific endothelin-1 binding sites in airway epithelial cells. AB - The effect of endothelin-1 (ET-1) on arachidonate metabolism in the respiratory epithelium was investigated in primary cultures of feline tracheal epithelial cells. Subconfluent epithelial cell cultures were stimulated by ET-1, and eicosanoid generation was determined by high performance liquid chromatography (HLPC) of 3H-labeled arachidonic acid (AA) metabolites and by radioimmunoassay (RIA) of corresponding nonradiolabeled HPLC elution. The HPLC chromatograms of [3H]AA-prelabeled samples revealed that ET-1 (10(-5) M) augmented the release of prostaglandin (PG) E2, 12-hydroxyeicosatetraenoic acid (HETE), PGF2 alpha, and AA. RIA of corresponding nonradiolabeled HPLC elution demonstrated a significantly increased release of PGE2, PGF2 alpha, and 12-HETE as well as 5 HETE in response to ET-1 stimulation. 5-HETE release from ET-1-stimulated cells was further identified by gas chromatography/mass spectrometry (GC/MS). The stimulating effect of ET-1 on AA metabolism was dose dependent (10(-5) to 10(-7) M) and peaked within 1 h with a progressive decline over the subsequent hours. Using 125I-labeled ET-1 as radioligand, the presence of specific binding sites for ET-1 was demonstrated in cultured feline tracheal epithelial cells. ET-1 binding reached equilibrium within 1 h at 37 degrees C. Scatchard analysis suggested the existence of two saturable binding sites, with the estimated equilibrium dissociation constant (Kd) of 35.3 pM and maximal binding capacity (Bmax) of 15.0 fmol/10(7) cells for the higher affinity binding site and Kd of 205.9 pM and Bmax of 35.0 fmol/10(7) cells for the lower affinity binding site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448019 TI - Alterations in nonhuman primate (M. nemestrina) lung proteoglycans during normal development and acute hyaline membrane disease. AB - Proteoglycans (PGs) and lung hyaluronan (HA) are important components of the lung matrix both during normal development and in response to injury. We combined morphologic and biochemical techniques to study changes in PG and HA in a developmental series of Macaca nemestrina lungs ranging from 62% gestation to 3 mo post-term (n = 16), in adult lungs (n = 6), and from prematurely delivered, mechanically ventilated monkeys with hyaline membrane disease (HMD) (n = 7). Three groups of cuprolinic blue-positive (CuB) precipitates, identified by size, location, and susceptibility to enzyme digestion were found in lungs from all animals. Immature alveolar interstitium is characterized by loosely woven collagen bundles and an abundance of large (100 to 200 nm) stained filaments representing chondroitin sulfate proteoglycans (CSPGs). As maturation proceeds, the interstitial matrix appears increasingly organized, with large collagen bundles associated with 20 nm CuB-stained deposits (dermatan sulfate proteoglycans, DSPGs), and fewer large CSPGs. Fetal alveolar basement membrane contains CuB-stained heparin sulfate proteoglycans (HSPGs) (10 nm) scattered throughout. Lung matrix from animals with HMD appeared to have a disruption of the collagen-DSPG relationship, in addition to an enrichment in large CSPG. Complementary biochemical analysis of lung PGs and HA was done. Minced lung parenchyma was cultured with [3H]-glucosamine and [35S]-sulfate for 24 h; PGs and HA were extracted and analyzed. While PG synthesis during development tended to be highest at 80% gestation, animals with HMD showed greatly increased synthesis, approximately 2.5-fold higher than comparable fetal animals. In the developmental series, [3H]-glucosamine incorporation into HA was maximal at term, falling abruptly thereafter. HMD animals, however, showed a 2.3-fold increase over controls in net HA synthesis. Extracted PGs were separated according to buoyant density by dissociative cesium chloride density gradient ultracentrifugation. Two peaks of 35S-labeled PGs were separated from each density gradient fraction by chromatography on Sepharose CL-4B. A large CSPG was the principal PG eluting in the voiding volume, while the second broad peak (K(av) = 0.42) contained a mixed population of CSPG, DSPG, and HSPGs, the proportions of which varied with age. Both ultrastructural and biochemical analyses indicate that production of a large, high buoyant density CSPG predominates in fetal lung tissue, and diminishes with developmental age. Synthesis of large CSPG is greatly increased in lung explants from prematurely delivered animals with HMD.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8448020 TI - T cell priming in situ by intratracheally instilled antigen-pulsed dendritic cells. AB - In the present study, splenic dendritic cells (DC) and alveolar macrophages (AM) were pulsed with antigen in vitro and subsequently intratracheally instilled to test whether these cells have the capacity to sensitize T cells in the draining lymph nodes of the lung. The data demonstrate that antigen-pulsed DC, instilled in the bronchoalveolar lumen, induce antigen-specific T cell priming in vivo in the draining lymph nodes. T cell priming is only seen with viable but not with killed antigen-pulsed DC. Amounts as low as 5 x 10(3) to 10 x 10(3) cells can still induce some responsiveness. In addition, it was found that instillation of viable as well as killed pulsed Ia-negative AM also leads to T cell priming, although about 10 times higher numbers of cells had to be used in comparison with DC. The results suggest that DC instilled in the bronchoalveolar lumen present antigen directly to naive T cells, whereas for AM other mechanisms are involved. PMID- 8448022 TI - Microtubule-organizing centers in higher plants. AB - Compelling evidence has recently been obtained for the idea that the nuclear surface of higher plant cells has a microtubule-nucleating function under cell cycle dependent control. Whatever the final organization of microtubules, they all seem to originate in the nuclear periphery. The spatial distribution of microtubules is a secondary process involving actin and microtubule-associated proteins, and other morphogenetic controls. How microtubules are nucleated and/or reorganized at the spindle poles during mitosis remains unknown. PMID- 8448021 TI - Unravelling the tangled web at the microtubule-organizing center. AB - The last year has seen dramatic progress in the use of genetic and biochemical approaches to identify microtubule-organizing center components. The use of vertebrate and invertebrate egg extracts has allowed the development of novel assays for centrosome duplication and activation. A variety of mutations in fungi are being used to sort out the pathway of spindle pole body duplication. PMID- 8448023 TI - Molecular biology of neuronal intermediate filaments. AB - In the past few years, several neuronal intermediate filament proteins have been characterized. While ongoing investigations have continued to shed light on their developmental expression, the importance of different domains of the proteins for assembly, the elements in their genes necessary for tissue-specific expression, and the role of phosphorylation of neurofilaments, the function(s) of these structures remain a matter of speculation. PMID- 8448024 TI - Mitosis: spindle assembly and chromosome motion. AB - New studies on mitosis demonstrate the complexity of interactions that contribute to chromosome motion and spindle assembly. Genetic and immunological approaches reveal the requirement for kinesin-related proteins during cell division in diverse cells. Observations of the dynamic behavior of microtubules demonstrate that their disassembly can produce sufficient force to move chromosomes in vitro, that their poleward movement, or flux, contributes to anaphase motion, and that the direction of anaphase motion can be reversed by induction of kinetochore microtubule elongation. PMID- 8448025 TI - Phenotypes of cytoskeletal mutants. AB - Phenotypic studies continue to contribute to an understanding of the functions of cytoskeletal proteins. Many of these studies indicate some degree of functional redundancy within a family of cytoskeletal proteins. Some surprises have emerged, such as suggestions of unexpected relationships between the actin and microtubule cytoskeletons. Finally, phenotypic studies have provided evidence for a function of intermediate filaments. PMID- 8448026 TI - Cytoplasm and cell motility. PMID- 8448027 TI - Intermediate filament structure and assembly. AB - Intermediate filaments are constructed from two-chain alpha-helical coiled-coil molecules arranged on an imperfect helical lattice. Filament structure and assembly can be influenced at several different structural levels, including molecular structure, oligomer formation and filament nucleation and elongation. Consequently, it can sometimes be difficult to interpret mutagenesis data unequivocally, although regions near the amino and carboxyl termini of the rod domain of the molecule are known to be important for the production of native filaments. Imperfections in molecular packing may be important in filament assembly and dynamics. PMID- 8448028 TI - Desmosomes and hemidesmosomes. AB - Desmosomes and hemidesmosomes are extremely different in their molecular composition. Most of the protein and glycoprotein components are products of members of multigene families, but show specialization for plaque formation and intermediate filament attachment. Desmosomal glycoproteins are more heterogeneous than previously suspected, with different isoforms showing tissue-specific and differentiation-related expression. Both types of junctions can be modulated in response to extracellular signals and may turn out to be involved in signal transduction. PMID- 8448029 TI - Actin molecular structure and function. AB - The understanding of actin structure and function has been improved by comparing the atomic structure of G-actin, the model of the F-actin structure, and the properties of actin mutants. Several aspects of actin structure have been tested and good progress has been made in mapping its myosin-binding sites. The dynamic properties of actin and genetic evaluation of its cellular function are attracting increasing attention. PMID- 8448030 TI - Actin isoforms. AB - The actin supergene family encodes a number of structurally related, but perhaps functionally distinct, protein isoforms that regulate contractile potential in muscle tissues and help to control the shape as well as the motility of non muscle cells. In spite of the documented conservation amongst isoactin genes and their encoded proteins, recent results of biochemical, antibody localization, molecular mutagenesis and isoactin gene replacement studies lend credence to the notion that functional differences amongst muscle and non-muscle actin isoforms exist. Furthermore, the discovery of a new class of actin isoforms, the actin related proteins, reveals that the actin gene and protein isoform family is more complex than was previously believed. PMID- 8448031 TI - Small actin-binding proteins: the beta-thymosin family. AB - Thymosin beta 4 is a major actin monomer binding protein present at high concentration in many vertebrate cells and cell lines. The interactions of actin with thymosin beta 4, actobindin and profilin are compared. Nine beta-thymosins have been identified; six have been shown to bind to actin. Regulation of the synthesis of thymosin beta 10 and thymosin beta 4 has been found in brain development and after stimulation of several cell types, respectively. The extracellular effects of thymosin beta 4 still need clarification. PMID- 8448032 TI - Caldesmon. AB - Recent research has led to an understanding of the in vitro properties of caldesmon, including the regulation of actomyosin ATPase activity, cross-linking between actin and myosin, enhancement of microfilament stability and stimulation of polymerization of actin. While it remains to be established whether caldesmon functions similarly in vivo, recent studies have suggested that smooth muscle caldesmon regulates the inhibition of vascular smooth muscle tone, and that non muscle caldesmon plays roles in the regulation of cell motility and cytoskeletal organization in three biological activities: granule movement, hormone secretion and reorganization of microfilaments during mitosis. PMID- 8448033 TI - Myosins. AB - The number and variety of myosins that have been identified has increased greatly over the past few years, and is still growing. Myosins have been classified into at least six distinct classes. Research during the last year has concentrated on identifying the roles of various myosins. PMID- 8448035 TI - Non-motor microtubule-associated proteins. AB - This past year, the structure and function of microtubule-associated proteins (MAPs) have been investigated in studies probing their phosphorylation, patterns of expression, and the function of the microtubule-binding domain. Cellular studies have also contributed new insights into the roles of these proteins in process outgrowth. PMID- 8448034 TI - Dystrophin and the membrane skeleton. AB - Recent studies have confirmed several predictions concerning the structure and possible function of dystrophin, including a direct interaction with F-actin and an indirect interaction with laminin via linkage through a transmembrane protein complex. The results of the past year support a role for dystrophin in linking the actin cytoskeleton with the extracellular matrix in striated muscle, but they have not explained its function in other tissues. PMID- 8448036 TI - Cytoplasmic microtubule-based motor proteins. AB - A multitude of microtubule-based motors drives diverse forms of intracellular transport and generates forces for maintaining the dynamic structural organization of cytoplasm. Recent work has illuminated the functions and mechanisms of action of some microtubule motors, and appears to have uncovered unforseen functional interactions between tubulin-based and actin-based systems. PMID- 8448037 TI - Physiological actions and clinical applications of transforming growth factor beta (TGF-beta). PMID- 8448038 TI - The trophic effect of the sympathetic nervous system on cells of the septal region of the basal forebrain. AB - The sympathetic nervous system exerts a trophic-mitogenic effect on C-1300 mouse neuroblastoma. We now report that the trophic factor present in freshly excised sympathetic ganglia from newborn rats enhances survival and process formation of the cells of the septal region of the rat basal forebrain. PMID- 8448039 TI - The NH2-terminal extension of high molecular weight forms of basic fibroblast growth factor (bFGF) is not essential for the binding of bFGF to nuclear chromatin in transfected NIH 3T3 cells. AB - Immunolocalization of basic fibroblast growth factor (bFGF) was investigated in NIH 3T3 cells transfected with a cDNA encoding for the 18 kD form of human bFGF (18 kD-bFGF) or with a bFGF cDNA encoding for both 18 kD-bFGF and NH2-terminal extended high molecular weight forms of bFGF (HMW-bFGFs). Nuclear and cytoplasmic bFGF-immunoreactivity was observed in both transfectants. Nuclear bFGF immunoreactivity was evenly distributed during interfase and associated with condensed chromosomes throughout the mitotic cycle. Cell fractionation, followed by Western blot analysis, confirmed the presence of 18 kD-bFGF and of HMW-bFGFs in the nucleus of transfected cells. Also, both 18-kD bFGF and HMW-bFGFs copurified with nuclear chromatin. After trypsin digestion, chromatin-bound bFGFs showed a rapid degradation of the nuclear-targeting NH2-terminal extension of HMW bFGFs which were converted to the 18 kD form. On the contrary, 18 kD-bFGF appeared to be trypsin-resistant when bound to nuclear chromatin or to isolated eukaryote DNA. Thus, our data indicate that: i) both 18 kD-bFGF and HMW-bFGFs localize into the nucleus of transfected NIH 3T3 cells and bind to nuclear chromatin; ii) the interaction of all bFGF isoforms with nuclear chromatin is mediated by one or more sequences present within the 18 kD form; iii) the chromatin-binding domain of HMW-bFGFs is distinct from their nuclear-targeting domain. PMID- 8448040 TI - [Anatomoclinical correlations of spinal muscular atrophy in infancy]. AB - Forty-three cases of infantile spinal muscular atrophy diagnosed in our department between 1977 to 1991 are presented. Following clinical-pathologic evaluation, 27 cases were included in type I, 7 in type II and 9 cases in type III. The most frequent pathologic finding was the presence of large groups of atrophic fibers and hypertrophy of isolated fibers in muscle biopsy. Enzyme study showed higher mean levels of CPK and aldolase in type I with respect to the other two. Likewise, a significant statistical difference was found in the age of onset of the different groups. Finally, the clinical classification of spinal muscular atrophies in infancy is discussed. PMID- 8448041 TI - [Thrombolytic therapy in cerebrovascular disease]. PMID- 8448042 TI - [Centronuclear myopathy]. AB - A 19 year-old patient, second child of a non consanguinous marriage, was evaluated because of the patient progressive mental retardation and muscular weakness from infancy. Six maternal uncles non had died of unknown cause in the first year of life, and his mother had 3 spontaneous miscarriages; the two sisters of the patient were healthy. Clinical examination demonstrated a severe mental retardation, discrete proximal muscular weakness as well as universal areflexia. The muscular enzymes were elevated and the electrophysiologic study showed normal neurographic parameters and abundant generalized spontaneous activity with a mixed type contraction pattern. Histologic examination of the muscle was diagnosed as myopathy with atrophy of type I fibers and central nuclei and upon cranial nuclear magnetic resonance (NMR) images suggestive of perinatal hypoxic-ischemic encephalopathy were observed. PMID- 8448043 TI - [Osmotic unbalance syndrome and neurological impairment due to cerebral edema]. PMID- 8448044 TI - [Capsular infarct caused by luetic arthritis]. PMID- 8448045 TI - [New magnetic resonance findings in the Meige syndrome]. PMID- 8448046 TI - [Diplopia as an ischemic transient attack]. PMID- 8448047 TI - [Neuropsychological impairment in closed head injury. Relationship between objective and subjective deficit]. AB - We have studied a group of patients who had suffered severe closed head injury. We have found that the presence of neuropsychological impairment was related with the duration of posttraumatic amnesia. The more frequent complaints were memory deficit, problems of attention and personality changes specially an increase in anxiety and aggressivity levels. All these impairments were confirmed by the neuropsychological assessment. We have found a strong relationship between the memory performance and the subjective complaints. We think that questionnaires exploring subjective complaints are useful in the neuropsychological evaluation of traumatic patients. PMID- 8448048 TI - [Intermittent acute porphyria in the region of Murcia]. AB - Forty-three cases of intermittent acute porphyria (IAP) in 19 families grouped along the riverside of the Segura River in the region of Murcia (1,000,000) were collected. Twenty nine cases had the typical clinical manifestations of the disease, 22 with analytic confirmation. Fourteen asymptomatic disease carriers were detected by determination of the uro-synthetase activity. Out of 22 hospitalized patients, 18 presented neurologic manifestations, 13 with polyneuropathy mainly of the proximal type. In some cases weakness extended distally. In the few cases in whom the polyneuropathy was initially distal there was never a Landry type of ascent. The most severe cases of polyneuropathy left characteristic sequelae in the hands. PMID- 8448049 TI - Freedom to choose. PMID- 8448050 TI - As job losses continue--what next? AB - If you had been unemployed during the Great Depression of the 1930s, would you have believed that you were living through just a hiccup in a long steady growth trend? Yet that was the case! Looked at from an historical perspective, our present recession is but the birth pangs of a new global order. PMID- 8448051 TI - Hepatitis B transmission. PMID- 8448052 TI - 'Caries and periapical pathology in an unerupted tooth'. PMID- 8448053 TI - 'Sarah's spots'. PMID- 8448054 TI - Poswillo. PMID- 8448055 TI - Vibration white finger. PMID- 8448056 TI - 'Whistle blowing'. PMID- 8448057 TI - Multiple mandibular multilocular radiolucencies. PMID- 8448058 TI - Specialisation in dentistry. PMID- 8448059 TI - A radiographic study of post-retained crowns in patients attending a dental hospital. AB - A total of 327 post-retained crowns were examined radiographically and a number of features were assessed including the length of post, length of remaining root filling, periapical condition, fit and angulation of the post and quality of root filling. The post length was equal to or greater than that of the crown in only 34% of cases. Although the majority of posts fitted well laterally, 43% did not extend longitudinally as far as the end of the prepared post hole. Some 20% deviated from the line of the root canal but the number of actual lateral perforations was small. A total of 47% of the teeth had areas of radiolucency around the root apices. A majority of root fillings were judged to be unsatisfactory and there was no radiographic evidence of any root filling at all in nearly 10% of cases. PMID- 8448060 TI - Recurrent ameloblastoma?--An historic case report and a review of the literature. AB - A case is described in which a patient who was originally treated by radical mandibular surgery including rib grafting, having been told that she had a dentigerous cyst, presented 49 years later with a follicular ameloblastoma. The case is discussed in an attempt to determine whether the initial diagnosis could have been ameloblastoma (if so, this demonstrates a long-term recurrence), whether this is a follicular ameloblastoma arising from remnants of an original dentigerous cyst, or whether this is an ameloblastoma, developing subsequently and coincidentally from adjacent dental lamina. This report is of historical interest, not only because of the long period of time that has elapsed between initial treatment and the present ameloblastoma, but also because of the eminent surgeons involved and the advanced techniques that they so proficiently carried out in 1942-1943. PMID- 8448061 TI - The response of 1578 school leavers to a campaign combining commercial, Health Boards' and GDPs' sponsorship in an effort to improve dental attendance. AB - A dental health promotion campaign was developed by Forth Valley Health Board in conjunction with the Scottish Health Education Group and the Department of Marketing at Strathclyde University. The aim was to encourage dental attendance among early school leavers. The emphasis was on the contribution of dental care to appearance and attractiveness. To highlight the importance of appearance, a major clothing retailer offered discounts on clothes to participants who made a dental visit. The impact of the campaign was evaluated by a questionnaire 3 months after its close. Recall of the campaign was high at 62% and 16% actually initiated a dental visit. However, only 2% claimed that the campaign was their main reason for attending. The project demonstrated the feasibility of collaboration between a commercial company and a health board in a health promotion effort. The results underline the difficulties in initiating a behaviour change, overcoming apathy and modifying the lack of felt need for dental care among the age group concerned. It does, however, suggest that there is potential for a more prolonged marketing effort. PMID- 8448062 TI - Patients' needs--more than meets the eye. AB - For many years, 'need' for dental care has been measured by assessing the extent of disease present in an individual's mouth. A person is viewed as requiring treatment if their oral tissues are damaged in any way by pathological processes or trauma. However, GDPs understand that patients often only attend for care when they experience symptoms or events which disrupt their life in some way, so that dental attendance relies upon a person feeling that they do not look, speak or feel 'well' in some way. PMID- 8448063 TI - Impairment of psychomotor function at modest plasma concentrations of carbamazepine after administration of the liquid suspension to naive subjects. AB - 1. The influence of pharmaceutical formulation on the plasma drug concentration time curve and the psychomotor responses to 400 mg carbamazepine has been assessed in 12 healthy male volunteers; three formulations and placebo were compared in a randomised, blind, crossover study. 2. The plasma concentration of carbamazepine rose to a maximum of 3-7 mg l-1 by 2-3 h after administration of the liquid suspension. Conventional and controlled release tablet formulations gave lower peaks at about 8 and 32 h, respectively. From 32 h onwards the plasma concentrations from the three formulations were indistinguishable. 3. Significant impairment of psychomotor function was observed after the liquid suspension only; subjective sedation was significant at 1 and 2 h and the critical flicker fusion frequency threshold was lowered at 1-8 h. Digit-symbol substitution, choice reaction time and body sway gave less conclusive evidence of impairment. 4. The results do not support the hypothesis that a psychomotor effect from carbamazepine is a threshold phenomenon with a critical plasma drug concentration at about 8 mg l-1. 5. A second hypothesis that rate of rise of plasma carbamazepine concentration has an important influence on psychomotor effect fits the observations. This interpretation is tentative since the use of a fixed dose of carbamazepine meant that differences due to rate of rise of drug concentration were confounded with differences due to peak height. PMID- 8448064 TI - The concentration-dependent disposition of intravenous p-aminohippurate in subjects with normal and impaired renal function. AB - 1. The disposition and kinetics of p-aminohippuric acid (PAH) were studied in 27 healthy male volunteers, 10 healthy female volunteers and 10 patients with chronic renal impairment following rapid intravenous injection of 10 mg kg-1. In addition, the renal clearances of PAH and its metabolite N-acetyl-PAH were measured in 10 of the healthy male volunteers following conventional administration of PAH by loading dose and constant infusion, and in another eight during sequential 'step-up' and 'step-down' infusions intended to maintain low, medium and high plasma concentrations below the threshold for onset of saturation of tubular transport. 2. PAH was eliminated rapidly with a mean half-life of less than 30 min in the healthy volunteers and 72 min in the renal patients. The corresponding estimates for acetyl-PAH were 49 and 153 min. In both groups the rate of disappearance of PAH slowed progressively over the period of observation and there was no true log-linear terminal elimination phase. 3. In the healthy volunteers about 50% of the dose was excreted in the urine in 30 min with quantitative recovery in 3 h. In 8 h, 17% of the dose was recovered as acetyl PAH. In the patients with renal impairment the 8 h recovery was only 83.6% of the dose with 26.9% of the total appearing as acetyl-PAH. 4. The volume of distribution (Vss) of PAH was 16-18 l in the healthy subjects and renal patients. Acetyl-PAH appeared to have a much larger distribution volume (mean 65.5 l in the healthy volunteers). 5. In the healthy volunteers the renal clearance of PAH fell dramatically from 599 +/- 115 ml min-1 1.73m-2 during the first hour after administration to 300 +/- 208 ml min-1 1.73 m-2 during the second hour (P < 0.001). The corresponding renal clearances of acetyl-PAH were 775 +/- 196 and 916 +/- 212 ml min-1 1.73 m-2. In the patients with renal impairment the renal clearance of PAH fell from 194 +/- 83 ml min-1 1.73 m-2 in the first hour to only 61 +/- 19 ml min-1 1.73 m-2 from 4 to 6 h. Over the same period there was no significant fall in the clearances of acetyl-PAH or total PAH (acetyl-PAH + PAH).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8448065 TI - Inhibition of human cytochrome P450 2D6 (CYP2D6) by methadone. AB - 1. In microsomes prepared from three human livers, methadone competitively inhibited the O-demethylation of dextromethorphan, a marker substrate for CYP2D6. The apparent Ki value of methadone ranged from 2.5 to 5 microM. 2. Two hundred and fifty-two (252) white Caucasians, including 210 unrelated healthy volunteers and 42 opiate abusers undergoing treatment with methadone were phenotyped using dextromethorphan as the marker drug. Although the frequency of poor metabolizers was similar in both groups, the extensive metabolizers among the opiate abusers tended to have higher O-demethylation metabolic ratios and to excrete less of the dose as dextromethorphan metabolites than control extensive metabolizer subjects. These data suggest inhibition of CYP2D6 by methadone in vivo as well. 3. Because methadone is widely used in the treatment of opiate abuse, inhibition of CYP2D6 activity in these patients might contribute to exaggerated response or unexpected toxicity from drugs that are substrates of this enzyme. PMID- 8448066 TI - Metabolic effects of lacidipine: a placebo-controlled study using the euglycaemic hyperinsulinaemic clamp. AB - 1. Twelve healthy male volunteers received lacidipine 4 mg and matching placebo, each for 2 weeks, in a randomised, double-blind crossover study, and attended on 4 study days to evaluate the effects of single and multiple dosing using the euglycaemic hyperinsulinaemic 'clamp'. 2. On each study day, a primed constant rate infusion of soluble insulin (1.5 mu kg-1 min-1) was administered for 180 min with a variable-rate infusion of 20% dextrose to maintain euglycaemia (5.2 mmol l 1). Whole-body insulin sensitivity was calculated during the past 40 min of the 'clamp'. At frequent intervals, measurements of BP and HR were recorded and venous blood samples collected for serum insulin, C-peptide, potassium, triglyceride (TG) and plasma noradrenaline concentrations. 3. Lacidipine was generally well tolerated and there were no adverse biochemical events. Mean values for insulin sensitivity +/- s.d. were 8.9 +/- 1.6 and 9.1 +/- 2.0 mg kg-1 min-1 after single doses of lacidipine and placebo respectively (95% CI, -1.0, 1.3), and correspondingly 9.6 +/- 2.1 and 9.7 +/- 1.5 mg kg-1 min-1 after 2 weeks (95% CI, -1.0, 1.3). 4. There was a significant reduction in fasting serum TG concentrations after 2 weeks of lacidipine: 0.7 +/- 0.3 mmol l-1 vs 0.9 +/- 0.6 (P < 0.001). However, changes in serum TG and potassium concentrations during the 'clamp' were not significantly different between the 4 study days. 5. Thus, in 'insulin sensitive' volunteers, lacidipine reduces fasting serum TG concentrations but has no effect on insulin-stimulated uptake of glucose, potassium and TG under euglycaemic hyperinsulinaemic conditions. PMID- 8448067 TI - Therapeutic consultation: a necessary adjunct to independent drug information. AB - 1. A therapeutic consultation service was implemented in 1984 to complement other methods of information and education on drug therapy for prescribers. 2. Up to 1991, 1,620 enquiries were received, 65% from our hospital and an increasing proportion from primary care (10%), other hospitals (6%), family planning centres (4%), and other sources (14%). 3. More than two-thirds (67%) were consultative enquiries, as opposed to demands for factual information, which needed knowledge of medical aspects of the case and clinical expertise. 4. 85% of enquiries were answered with a written report including relevant references and as conclusive as possible recommendations. 5. More discussion of therapeutic consultation is needed, and aspects for discussion are suggested. PMID- 8448068 TI - Evening vs morning isradipine sustained release in essential hypertension: a double-blind study with 24 h ambulatory monitoring. AB - A randomized, double-blind, placebo controlled study evaluated the effects on 24 h ambulatory blood pressure (ABP) of isradipine sustained release (I-SRO) administered once daily, in the morning (AM) or in the evening (PM). Eighteen uncomplicated essential hypertensives (10 men, mean age 55 +/- 6 years) with casual sitting DBP 96-110 mm Hg received, according to a triple-way crossover design, I-SRO 5 mg AM, or 5 mg PM, or placebo for 4 weeks. A 24 h ABP monitoring (Spacelabs 90207) was carried out at the end of each treatment. Twenty-four hour BP was 145.3/89.8 mm Hg after randomized placebo. AM and PM I-SRO significantly reduced 24 h BP, by 13.7/8.7 and 12.9/8.2 mm Hg respectively. Daytime (07.00 h 23.00 h) BP significantly decreased by 15.0/9.7 mm Hg with AM and 13.2/8.7 mm Hg with PM regimen; night-time BP (23.00 h-07.00 h) significantly decreased by 11.6/7.1 and 12.3/7.4 mm Hg, respectively. Nocturnal nadir BP values were 132.6/78.1 after randomized placebo, 120.9/71.4 after AM I-SRO and 121.0/72.4 mm Hg after PM I-SRO. Morning peak BP values were 154.6/96.9, 139.5/87.6 and 137.5/85.5 mm Hg, respectively. Mean BP values in the early morning hours (i.e. between 03.00 h and 08.00 h) were significantly decreased by 12.1/7.3 mm Hg after AM and 14.3/7.9 mm Hg after PM intake. No significant differences were detected in the BP lowering effect of the two I-SRO regimens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448069 TI - Effect of an inhaled histamine H3-receptor agonist on airway responses to sodium metabisulphite in asthma. AB - Histamine H3-receptor agonists inhibit excitatory neuro-transmission in human and guinea-pig airways. Since neural bronchoconstriction may be important in asthma we have studied the effect of a specific H3-receptor agonist R-alpha methylhistamine (alpha MeHA) on bronchoconstriction induced by the inhaled irritant sodium metabisulphite (MBS) in six mild asthmatic subjects in a randomised double-blind crossover study. Subjects received either alpha MeHA, 10 mg (as a chloride salt) or matched placebo (P) and were then challenged with doubling concentrations of MBS (0.3-80 mg ml-1) nebulised from a dosimeter at 5 min intervals with measurement of specific airway conductance (sGaw) and FEV1 at 2 and 4 min respectively after each inhalation. There was no effect of alpha MeHA on baseline airway calibre and the log concentrations of MBS required to lower sGaw by 50% (log PC50) and FEV1 by 20% (log PC20) were not significantly different after alpha MeHA when compared with placebo, suggesting that selective stimulation of airway H3-receptors does not inhibit MBS-induced bronchoconstriction. PMID- 8448070 TI - Paracetamol elimination in patients with non-insulin dependent diabetes mellitus. AB - The pharmacokinetics and metabolism of an intravenous dose (500 mg) of paracetamol were studied in a group of non-insulin dependent diabetic patients (n = 10) and in a group of healthy control subjects (n = 9). Paracetamol clearance, half-life and the partial clearance to paracetamol glucuronide were not significantly different, but the partial clearance to paracetamol sulphate was significantly reduced (62 +/- 18 vs 86 +/- 17 ml h-1 kg-1 (mean +/- s.d.)) and the renal clearance of paracetamol was significantly increased (56 +/- 20 vs 22 +/- 6 ml h-1 kg-1 (mean +/- s.d.)) in the non-insulin dependent diabetic patients, compared with the control group. PMID- 8448071 TI - The effects of liver and renal disease on stereoselective serum binding of flurbiprofen. AB - Stereoselectivity in the serum binding of flurbiprofen, a non-steroidal anti inflammatory drug which is highly bound to albumin, was studied in patients with liver and renal disease. Subjects with renal disease or liver disease with ascites had significantly lower serum albumin concentrations than normals, resulting in higher free fractions of both the R(-) and S(+) enantiomers of flurbiprofen as determined by equilibrium dialysis. The ratio (+/- s.d.) of R/S flurbiprofen free fractions was lower in the subjects with ascites (0.714 +/- 0.298) than in those without ascites (0.796 +/- 0.090) (P < 0.05). PMID- 8448072 TI - A comparison of the effects of captopril and enalapril on skin responses to intradermal bradykinin and skin blood flow in the human forearm. AB - 1. The effects of captopril and enalapril on skin responses to intradermal injections of bradykinin and skin blood flow in the forearm were investigated in this randomised, double-blind, placebo-controlled, cross-over study. 2. Intradermal injections of 0, 1, 2.5 and 5 micrograms of bradykinin in 0.9% sodium chloride were made into the forearm of twelve healthy volunteers before and at 2, 6 and 24 h after single oral doses of 25 mg captopril, 10 mg enalapril or placebo. Forearm skin blood flow was measured by the technique of laser Doppler flowmetry (LDF) before the injections were made and the skin responses evaluated at 15 min after injections of bradykinin by measurement of cutaneous blood flow outside the induced weal, erythema area and weal volume. 3. The bradykinin induced cutaneous responses measured by LDF, erythema area and weal volume increased with incremental bradykinin dose. Compared with placebo, captopril significantly augmented the cutaneous vasodilator effects of bradykinin, measured by LDF and erythema area, at 2 h and the weal responses at 2 and 6 h. Enalapril enhanced the vasodilator responses to bradykinin at 2 and 6 h and the weal responses at 2, 6 and 24 h. Neither captopril nor enalapril significantly affected forearm skin blood flow. 4. This study showed that captopril and enalapril potentiated the effects of intradermal bradykinin both with respect to blood flow changes and weal formation in keeping with effective kininase II inhibition and the time course of these changes are consistent with enalapril being a longer acting drug than captopril. Captopril and enalapril exerted no influence on forearm skin blood flow measured by LDF. PMID- 8448073 TI - Absolute configuration of (+)-cis-2,3-dihydro-2-[(methylamino)methyl]-1- [4 (trifluoromethyl)phenoxy]-1H-indene hydrochloride, a chiral serotonin uptake inhibitor. AB - The absolute configuration of (+)-cis-2,3-dihydro-2[(methylamino)methyl]- 1-[4 (trifluoromethyl)phenoxy]-1H-indene hydrochloride, the more active enantiomer of a new serotonin inhibitor, was established as 1S,2S. This assignment was based on the application of the benzene sector and chirality rules to the interpretation of the inhibitor's circular dichroism spectrum and the spectra of other related chiral 1-substituted 2,3-dihydro-1H-indenes. PMID- 8448074 TI - Stereoselective hydrolysis of triglycerides by animal and microbial lipases. AB - In the present paper, a study on the stereoselectivity of 25 lipases of animal and microbial origin towards homogeneous prochiral triglycerides is presented. All the lipases tested catalyse the hydrolysis of the chemically alike but sterically nonequivalent ester groups in trioctanoin and triolein with different degrees of stereobias, depending on the fatty acyl chain length of the substrate (Rogalska et al., J. Biol. Chem. 256:20271-20276, 1990). Hydrolysis of the sn-2 ester group is catalysed by very few lipases and only Candida antarctica A shows a clear preference for this position. Most of the lipases investigated (12 with trioctanoin and 16 with triolein) showed a preference for the sn-1 position. Using trioctanoin as substrate we observed a total stereoselectivity for position sn-1 with Pseudomonas sp. and Pseudomonas aeruginosa and for position sn-3 with Candida antarctica B. This was not the case with triolein as substrate. Among the 23 lipases studied here and the other two lipases described previously (Rogalska et al., J. Biol. Chem. 256:20271-20276, 1990), 17 show a higher stereoselectivity with trioctanoin than with triolein. With guinea pig pancreatic lipase and with three mold lipases (Geotrichum candidum M, Geotrichum candidum A, and Candida antarctica B), the preference switches from sn-3 to sn-1 when the acyl chain length increases from eight to 18 carbon atoms. The main conclusion to emerge from the present study is that the specific stereopreference of each lipase for a given substrate under given lipolytic conditions can be said to be its fingerprint. PMID- 8448076 TI - Dracunculiasis. Update, 1992. PMID- 8448075 TI - Stereoselective analysis of ketorolac in human plasma by high-performance liquid chromatography. AB - A high-performance liquid chromatographic (HPLC) analytical method is described for the quantification of the (R)- and (S)-enantiomers of ketorolac when present together in human plasma. The method involves derivatization with thionyl chloride/(S)-1-phenylethylamine and subsequent reversed-phase chromatography of the diastereomeric (S)-1-phenylethylamides of (R)- and (S)-ketorolac. The method is suitable for the analysis of large numbers of plasma samples and has been applied in this report to a pharmacokinetic study of ketorolac enantiomers upon intramuscular administration of racemic drug to a human subject. The limit of quantification for each enantiomer of ketorolac is 50 ng/ml (signal-to-noise ratio > 10). PMID- 8448077 TI - Global programme on AIDS. Profile of the HIV/AIDS epidemic. PMID- 8448078 TI - 'ESMO in the new Europe'. Presidential address, Lyon, November 1992. PMID- 8448079 TI - Escalating drug delivery in cancer chemotherapy: a review of concepts and practice--Part 2. PMID- 8448080 TI - Hodgkin's disease: study of treatment intensities and incidences of second malignancies. AB - BACKGROUND: Advances in radiotherapy and chemotherapy have gradually increased cure rates for patients with Hodgkin's disease. With improved long-term survivals, increases in observed second malignancies over those of the general population have been reported as early as 1972. Recently, a number of investigators have suggested that the relative importance of recognized risk factors contributing to the development of acute myelogenous leukemia (AML), non Hodgkin's lymphomas, and solid tumors may be different. Our study is concerned with the influence of various risk factors on patients who have been treated with modern radiotherapy and combination chemotherapy between 1966 and 1987. PATIENTS AND METHODS: We reviewed the records of 1,022 patients with Hodgkin's disease of whom 1,013 had sufficient data for analysis. Kaplan-Meier methodology was used to calculate overall and determinate survivals and occurrences of acute myelogenous leukemia, non-Hodgkin's lymphoma, and solid tumors. The observed to expected incidences, calculated from the SEER incidence and population files for 1976, were compared. Using Cox's proportional hazards model, the following were analyzed singly for risk significance for the entire population: age, stage, splenectomy, treatment modality, treatment intensity, and number of treated relapses. Separate analyses were performed to determine the relative risks for subsets of the population. These included pelvic radiotherapy for those with stage III disease and specific alkylating agents for patients who were treated with chemotherapy only. RESULTS: Sixty-six instances of second malignancy were documented as follows: AML 14, non-Hodgkin's lymphoma 14, and solid tumors 38. The overall incidence of second malignancy was significantly greater than the expected incidence of 21.75 (p = 0.0001) and it was also significant for AML, non Hodgkin's lymphoma and solid tumors. Analyses for risk of second malignancy demonstrated that age > or = 40 years, stage III or stage IV disease, and treatment with chemotherapy only were all associated with a significantly higher risk of second malignancy than any of the other factors. However, only treatment with regimens containing nitrogen mustard had a significantly higher risk for second malignancy. Treatment intensity and number of treated relapses had no specific effect on risk. Joint modeling of age, stage, and treatment showed that the combination of age and stage was the most significant risk factor for AML and non-Hodgkin's lymphoma (p = < 0.0003). However, only age was important for solid tumors. CONCLUSIONS: Our analysis suggests that the most critical host factor for developing a second malignancy was age. The fact that patients with stages III and IV disease had an increased risk of second malignancy regardless of age suggests that biologic factors related to the tumor also may have been significant. However, it is possible that the effect of treatment was hidden by stage. PMID- 8448081 TI - The influence of patient characteristics on the appropriateness of surgical treatment for breast cancer patients. Progetto Oncologia Femminile. AB - BACKGROUND: Within the framework of a multi-annual educational intervention sponsored by the Ministry of Health and regional health authorities, patterns of the care delivered to breast cancer patients in Italian general hospitals were monitored in order to identify areas of practice whose quality was in need of improvement. DESIGN: Information on the diagnostic and therapeutic procedures in 63 general hospitals in eight Italian regions performed in 1724 consecutive breast cancer patients were retrospectively gathered from medical records. Quality of care was assessed by a diagnostic and therapeutic score based on the observed degree of compliance with previously established courses of action. RESULTS: The median value of the overall diagnostic and staging score was 60%. About one-third of surgical operations (38%) were inappropriate: one-fourth (24%) of patients with stage I-II disease had unnecessarily radical surgery (i.e., Halsted mastectomy), and limited surgery in patients with small tumors (i.e., < or = 2 cm) was under utilized. Chronological age influenced physicians' behaviour: elderly patients were more likely to have a less intensive diagnostic work-up and less appropriate surgical treatment (with more frequent performance of an unnecessary radical operation and a less frequent utilization of limited surgery), independently of their overall health status. The presence of one or more co-existent diseases was associated with a failure to undergo axillary clearance and with a lower utilization of conservative surgery independently of age. CONCLUSION: In accord with others, this study confirms the existence of a clinically important effect of patient age on diagnostic and therapeutic behaviour and the use of unnecessarily radical surgery procedures. The paper discusses the implications of these findings for the next stage of the educational project, in which practice guidelines will be developed and implemented to improve the quality of care for breast cancer patients. PMID- 8448082 TI - Interferon instillation for malignant pleural effusions. AB - BACKGROUND: Malignant pleural effusions can be managed in various ways including instillation of antineoplastic agents. Instillations of alfa interferon-2b (IFN alpha 2b) have been utilized with success in various loco-regional malignancies suggesting a possible role in management of pleural effusions. This trial was designed to evaluate the tolerability and efficacy of intrapleural IFN-alpha 2b instillations in this situation. PATIENTS AND METHODS: Twenty-three patients with cytologically proven malignant pleural effusions were given IFN-alpha 2b 50 x 10(6) units in 50 ml normal saline (NS) by intrapleural instillation after partial or complete clearance of effusions by percutaneous aspiration or chest tube drainage. For persistent or recurrent effusions, instillations were repeated with dose escalation to 75 x 10(6) units. Patients were assessed and monitored by regular clinical examinations, chest radiographs, biochemical and hematological parameters and assays of lymphocyte subpopulations until relapse or death in each case. RESULTS: Fourteen of 20 evaluable patients (70%) had responses lasting for a median of 6 months; there were 8 complete responses (CR) and 6 partial responses (PR). In 6 CR patients the effusions did not recur after the first instillation. In 2 of 6 other patients, the second instillation was successful in inducing CR. Intrapleural instillation of IFN-alpha 2b was well tolerated, no grade 4 toxicities were encountered. There were no significant effects on any of the studied parameters at the initial dose level; however, grade 3 neutropenia occurred with the escalated dose. The most common toxicity was flu-like syndrome, after 70% of the instillations. CONCLUSIONS: Intrapleural instillation of IFN alpha 2b produced an encouraging response rate without significant toxicities. This approach may warrant additional phase II or phase III comparative clinical studies. PMID- 8448083 TI - CMV front-line chemotherapy in transitional bladder carcinoma. AB - BACKGROUND: Despite standard treatment, surgery and/or radiotherapy, most patients with muscle invasive bladder carcinoma die early of distant metastasis. CMV chemotherapy has demonstrated a high response rate with moderate toxicity in advanced bladder carcinoma. In an attempt to eradicate undetectable metastatic disease and to avoid cystectomies, 36 patients were given up-front CMV. MATERIALS AND METHODS: The patients were 34 males and 2 females with a median age of 62 years (45-75); performance status 0-1 (WHO) in 34 patients; histology: 34 transitional carcinomas and 2 anaplastic carcinomas (grade II: 8, grade III: 28). Clinical staging was T2-3a: 19 patients, T3b: 14 patients and T4: 3 patients. Nineteen patients had complete trans-urethral resections (TUR) at diagnosis. The multimodal protocol started with 3 CMV courses (cisplatin 100 mg/m2 i.v. d 1, methotrexate 30 mg/m2 i.v. d 1, 8 and vinblastine 4 mg/m2 i.v. d 1, 8 every 3 weeks). Patients who yielded clinical complete responses (cCR) by cystoscopy, TUR biopsies and imaging techniques were given 3 additional courses. Cystectomy was performed in non-cCR patients and as salvage treatment. RESULTS: Following 3 CMV cycles, 29 patients (81%) responded (20 cCR and 9 cPR) and 7 (19%) did not (NR). Currently, with a median follow-up of 23.5 months (13-59), 13 have died and 23 are alive, 12 of whom retain their bladders. The projected overall survival is 51% at 4.5 years. Grade 3-4 hematological toxicity was presented in 8% of the cycles. No toxic deaths were observed. CONCLUSION: The CMV regimen, after TUR, produces a high response rate with tolerable toxicity. Bladders could be preserved in half of the CR patients. PMID- 8448084 TI - Erythropoietin treatment for chronic anemia of selected hematological malignancies and solid tumors. AB - BACKGROUND: Neoplasias, especially in their more advanced stages, are often associated with chronic anemia of malignancy which impairs the patient's physical ability and quality of life. PATIENTS AND METHODS: Forty-two patients with chronic anemia associated with hematological malignancies (18 multiple myelomas, 10 myelodysplastic syndromes) or solid tumors (9 breast cancers, 5 colon cancers) were treated with 150-300 units/kg rHuEPO for a median time period of 16 weeks. Response was defined as an increase of the initial hemoglobin level by at least 2 g/dl. RESULTS: The response rates for solid tumors were comparable (44.4% and 40% for breast cancer and colon cancer, respectively), whilst the response in patients with hematological malignancies depended strongly on the disease entity (77.8% for multiple myeloma, 10% for myelodysplastic syndrome). Pretreatment serum levels of endogenous erythropoietin (EPO) were significantly higher in non responding patients than in responders. During rHuEPO therapy, EPO levels in non responders increased even further, while they remained basically unchanged in responding patients. In responders, the WHO performance status before the start of rHuEPO therapy was more favorable and showed impressive improvement during the course of treatment. The median survival time of responders was 28.0 months as compared to only 9.2 months for non-responders. Clinical symptoms of anemia subsided or at least considerably improved under successful rHuEPO therapy. With the exception of occasional flu-like symptoms, no undesirable effects of rHuEPO treatment were observed. CONCLUSIONS: In conclusion, rHuEPO treatment corrected anemia of malignancy both in patients with hematologic disease and in those with solid tumors, but responsiveness varied considerably amongst the different disease entities. PMID- 8448085 TI - Second-look laparotomy in the management of patients after radical surgery for ovarian cancer. AB - BACKGROUND: Radically excised ovarian cancers present an unsolved problem with regard to the value of routine second-look operation. This study presents the outcome of second-look operations in an effort to help elucidate this problem. PATIENTS AND METHODS: Twenty-eight patients who underwent radical surgery for ovarian cancer stage IC-IIIA were given adjuvant chemotherapy with cyclophosphamide 500 mg/m2 i.v., adriamycin 40 mg/m2 i.v. and 5-fluorouracil 500 mg/m2 i.v., all administered on days 1 and 8 every 4 weeks until achievement of a cumulative adriamycin dose of 400 mg/m2. It was planned that second-look laparotomy would be performed 10-12 months after the primary operation. RESULTS: Four of 28 patients (14.3%) had positive findings at second-look laparotomy. Two of these 4 patients had only microscopic disease, and after second-line chemotherapy including cisplatin one of them is clinically free of tumor 50 months after the primary operation. Two of 28 patients had clinical recurrences before the planned second-look operation. Four of the 22 patients (18.2%) with negative second-look operations developed recurrent disease within a median time of 12 months later. The 5-year survival rate for all 28 patients was 67%. CONCLUSION: Although a small group of patients may benefit from a strategy that includes delayed second-look operation, we conclude that this should not be a routine procedure in the management of patients who undergo radical surgery for ovarian cancer. PMID- 8448086 TI - A phase II trial of a chemotherapy combination in elderly patients with aggressive lymphoma. PMID- 8448087 TI - Vascuport catheter migration. A serious complication of long term venous access. PMID- 8448089 TI - Hodgkin's disease and second malignancies. PMID- 8448088 TI - Unexpected fatal toxicity related to low-dose leucovorin with 5-fluorouracil treatment in metastatic colorectal cancer. PMID- 8448090 TI - On the underutilization of breast-conserving surgery for the treatment of breast cancer. PMID- 8448091 TI - 1992 ASRA Lecture. Intravenous regional anesthesia: nerve block by multiple mechanisms. PMID- 8448093 TI - Reevaluation of the sciatic nerve block. AB - BACKGROUND AND OBJECTIVES: Sciatic nerve blocks are perceived as unreliable, technically demanding, and uncomfortable. With strict criteria to define success rates, we designed a study to examine the efficacy of two techniques of sciatic nerve block. METHODS: All blocks were performed by a novice in sedated patients using an insulated needle and a nerve stimulator. RESULTS: Overall success with both techniques was 87.5%. One transient neurologic deficit attributed to the sciatic nerve block was observed; otherwise, the technique provided satisfactory anesthesia without complications. CONCLUSIONS: Patient acceptance was excellent. PMID- 8448092 TI - Interadductor approach to obturator nerve blockade for spastic conditions of adductor thigh muscles. AB - BACKGROUND AND OBJECTIVES: The authors describe a new approach for the management of adductor muscle spasm associated with multiple sclerosis and paraplegia. METHODS: An obturator nerve block was performed by needle insertion behind the upper end of the adductor longus muscle; the needle was directed laterally, with slight upward and posterior inclination, toward the obturator canal. The obturator nerve was identified by its response to nerve stimulation. An initial diagnostic block using 5 mL of 2.0% lidocaine followed by two or three prognostic blocks using 5 mL of 0.5% bupivacaine and 1:200,000 epinephrine were performed. In the final block, 5 mL of 6.0% phenol in glycerin was injected. RESULTS: Evaluation of the efficacy of the block was achieved in terms of its success rate, the degree of alleviation of muscle spasm, the improvement of gait in the patients with multiple sclerosis, and the facilitation of nursing hygienic care in bedridden patients. In comparison with the traditional approach, the success rate and improvements were highly significant. CONCLUSIONS: The interadductor approach is a new approach based on the anatomy of the obturator nerve trunk, which, though in the obturator canal, is shielded by its osseous part from the anteroposterior perspective of the traditional approach. The interadductor approach allows needle positioning inside the obturator canal through a mediolateral perspective, thus facilitating the blockade of the obturator nerve trunk before it branches immediately outside the canal. The new approach proved to be successful, reproducible and without complications. PMID- 8448094 TI - The effect of cardiac output on intraoperative blood loss during total hip arthroplasty. AB - BACKGROUND AND OBJECTIVES: It is not clear whether cardiac output affects intraoperative blood loss under epidural hypotensive anesthesia. METHODS: Thirty patients undergoing primary total hip arthroplasty were randomly assigned to receive intravenous infusions of either low-dose epinephrine or phenylephrine to maintain mean arterial pressure at 50 to 60 mm Hg throughout surgery under lumbar epidural anesthesia. Patients were monitored with radial artery and thermodilution pulmonary artery catheters. Hemodynamic parameters were measured every 10 minutes during surgery, and blood loss was estimated by a blinded observer weighing sponges. RESULTS: Mean arterial pressure was similar between groups. Cardiac output remained unchanged in patients receiving low-dose epinephrine but declined significantly in patients receiving phenylephrine (p = 0.0001). Blood loss was 228 and 236 mL in patients receiving low-dose epinephrine and phenylephrine, respectively (p = 0.86). No correlation was observed between cardiac output and blood loss at any point during surgery. CONCLUSIONS: Cardiac output is not a factor influencing blood loss during hypotensive epidural anesthesia in elderly patients undergoing primary total hip arthroplasty. PMID- 8448095 TI - Patient acceptance of interscalene block for shoulder surgery. AB - BACKGROUND AND OBJECTIVES: Regional anesthesia can be applied to shoulder surgery with an expected high success rate. To determine the level of patient satisfaction with regional anesthesia, we studied a group of patients who had undergone shoulder surgery more than once, with general anesthesia on one occasion and regional on another. METHODS: Twenty-five consecutive patients with prior shoulder surgery under general anesthesia (GA) willing to receive interscalene brachial plexus anesthesia (ISB) were identified. On postoperative day one, a questionnaire was administered. Data were evaluated with McNemar's test and chi-square analysis and considered significant at p < 0.05. RESULTS: There were no differences in sedation or patient preparation between GA and ISB. ISB was tolerable during placement, and no patients complained of being aware or inadequately sedated. With ISB, there was better recovery room pain control, less nausea, and less vomiting. Overall, the patients preferred ISB. CONCLUSIONS: Interscalene brachial plexus block is well accepted by patients for reconstructive shoulder surgery. PMID- 8448096 TI - Extensive application of epidural anesthesia and analgesia in a university hospital: incidence of complications related to technique. AB - BACKGROUND AND OBJECTIVES: The authors report the role of epidural anesthesia and analgesia (EAA) and the incidence of epidural puncture-related complications in a university hospital in Japan. METHODS: Epidural anesthesia and analgesia was the major (39.7%) technique when administering 40,010 anesthetics. For the upper and the lower abdominal procedures, EAA was the major anesthetic technique in 79.5%, and 71.1% of these were carried out without potent inhaled anesthetics or long acting muscle relaxants, and without endotracheal intubation. RESULTS: Epidural anesthesia and analgesia-related complications included failure to produce anesthesia on the first attempt (4.1%), bleeding/intravascular cannulation (0.67%), unintentional dural puncture (0.61%), paresthesia (0.16%), and local anesthetic toxicity (0.12%). CONCLUSIONS: The incidence of EAA-related complications was greater with lumbar than with thoracic puncture. Four patients had transient neuropathy related to epidural puncture, but no serious neurologic complications occurred. PMID- 8448097 TI - Thoracic epidural bupivacaine plus sufentanil: high concentration/low volume versus low concentration/high volume. AB - BACKGROUND AND OBJECTIVES: To compare the postoperative analgesic and side effects of a continuous epidural infusion of bupivacaine with sufentanil: high concentration/low volume versus low concentration/high volume. METHODS: In a prospective study, 30 patients scheduled for thoracic surgery had a thoracic epidural catheter inserted. Postoperative analgesia was provided by a continuous epidural infusion for 3 days. The patients were randomly divided into two groups: the low volume (LV) group (1.5 to 2 mL per hour of a combination of bupivacaine 0.5% with sufentanil 4 micrograms.mL-1) and the high volume (HV) group (6 to 8 mL per hour of a combination of bupivacaine 0.125% with sufentanil 1 microgram.mL 1). RESULTS: The visual analogue scales were not different at rest or with exercise on days 1, 2, or 3. Supplemental analgesia by epidural catheter was necessary in half the patients in both groups. In two patients in the HV group and five patients in the LV group, a PaCO2 greater than mm Hg (7 kPa) was observed the first postoperative hour. Only on day 1 was the mean PaCO2 significantly increased in both groups (5.9 mm Hg [0.7] kPa in the LV group, and 6.0 mm Hg [0.4] kPa in the HV group) compared to the mean preoperative PaCO2 (5.1 mm Hg [0.5] kPa and 4.7 mm Hg [0.6] kPa). Between the groups there was no significant difference in PaCO2 at any time. CONCLUSIONS: With the thoracic epidural administration of bupivacaine and sufentanil for postoperative analgesia, the total dose is more important than the concentration or the volume of the solution. PMID- 8448098 TI - Level of injection in spinal anesthesia: effect on sensory anesthetic level. AB - BACKGROUND AND OBJECTIVES: A prospective, randomized study was performed to investigate the influence of the level of injection on sensory anesthesia when bupivacaine 0.5% adjusted to 37.0 C was used. METHODS: Three milliliters of plain bupivacaine 0.5% were injected at either the L2-3 interspace or the L4-5 interspace. There were 10 patients in each group. The patients were kept sitting for 2 minutes after injection. RESULTS: No significant difference in maximal level of sensory anesthesia was found (p = 0.123). CONCLUSION: These preliminary results indicate that if a higher level of injection is more suitable for anatomic reasons, it can safely be used without the risk of a much higher level of sensory blockade. PMID- 8448099 TI - Postdural puncture headache after continuous spinal anesthesia with 18-gauge and 20-gauge needles. AB - BACKGROUND AND OBJECTIVES: To evaluate the incidence of postdural puncture headache (PDPH) associated with continuous spinal anesthesia, 200 male patients (mean age 65 years) were randomly assigned to receive spinal anesthesia in one of three ways: group 1, 50 patients with an 18-gauge Tuohy-Schliff needle/20-gauge catheter combination; group 2, 50 patients with a newly developed 20-gauge Quincke point needle/24-gauge catheter combination; and group 3, 100 patients (control group, single injection spinal anesthesia) with a 22-gauge Quincke point needle. METHODS: Every patient was followed up for 7 days postoperatively. RESULTS: The incidence of PDPH was 6% with each continuous technique and 2% in the control group (difference not statistically significant). One group 1 patient who required an initial dose of 35 mg of tetracaine and 100 mg of lidocaine has a persistent, incomplete S4-5 sensory nerve deficit. CONCLUSIONS: The incidence of PDPH associated with continuous spinal anesthesia is acceptable in appropriate clinical circumstances, but large initial doses of local anesthetic should not be administered. PMID- 8448100 TI - Continuous spinal anesthesia: dose requirements and characteristics of the block. AB - BACKGROUND AND OBJECTIVES: A fine-bore 28G CoSpan spinal catheter was used to provide continuous spinal anesthesia for major upper and lower abdominal, peripheral vascular, and orthopedic surgery in 90 patients, aged 31-91 years. METHODS: Initial doses (0.5-2.0 mL) of hyperbaric bupivacaine 0.5% were given and followed, if needed, by additional doses of 0.5-1.0 mL to achieve a satisfactory blockade for the proposed type of surgery. The incidence of hypotension, ambulatory postdural puncture headache, and technical problems encountered with insertion of the spinal catheters were recorded. RESULTS: The technique of continuous spinal anesthesia was successful and easy to learn. Satisfactory sensory and motor blockade was achieved within 12-18 minutes, and surprisingly small amounts were needed in those patients undergoing limb surgery. CONCLUSIONS: Mild postdural puncture headache occurred in four patients, but none of the patients required blood patch. One catheter broke during removal; since then, it has been our policy to remove a catheter with the patient in a flexed position. PMID- 8448101 TI - Exogenous and endogenous plasma levels of epinephrine during dental treatment under local anesthesia. AB - BACKGROUND AND OBJECTIVES: To determine serum levels of catecholamines after local anesthesia for dental treatment, we used tritium-labeled epinephrine as a vasoconstrictor for dental local anesthesia. METHODS: Twenty healthy male outpatients undergoing standardized dental treatment (deep scaling) were studied. In all patients, only one quadrant was anesthetized even though the treatment was performed on all teeth. Two milliliters of articaine 4% (amide anesthetic) with 20 micrograms epinephrine was used as local anesthetic. Of the total epinephrine administered, 1.2% (100 microCi) consisted of tritium-labeled epinephrine. Blood samples were drawn through a central venous catheter before and at frequent intervals after the local anesthetic solution was administered. RESULTS: A dramatic increase in exogenous epinephrine was observed in four patients during injection (up to 6937 pg/mL). The other 16 patients demonstrated a continuous increase in applied epinephrine that peaked on average at the 7th minute (631.5 +/- 41.4 pg/mL). A second increase occurred after the beginning of the dental procedure. The mean total epinephrine levels were always higher than those of the applied epinephrine. Extrasystoles were observed in two of four and tachycardia in three of four patients with high plasma levels of applied epinephrine. Increases in total epinephrine were associated with exogenous catecholamine administration, whereas the dental treatment did not significantly influence the plasma levels. CONCLUSION: Despite aspiration in 20% of the patients, an unintended intravascular injection occurred. Although healthy young men tolerated large increases in central plasma epinephrine levels surprisingly well, this may not be the case in patients with concurrent cardiovascular disease. Patients at cardiovascular risk should be under continuous monitoring when an epinephrine containing solution is applied. PMID- 8448102 TI - Superior hypogastric plexus block using a single needle and computed tomography guidance. PMID- 8448103 TI - Gaston Labat and the American Board of Anesthesiology. PMID- 8448104 TI - 3-in-1 blocks and continuous 3-in-1 blocks. PMID- 8448105 TI - Myosin-ATP chemomechanics. AB - The hydrodynamic size of rabbit skeletal muscle myosin subfragment 1 (S1) is decreased when S1 and MgATP form the steady-state intermediate S1-MgADP,P(i). The rotational decay time, tau, determined by transient electrical birefringence techniques was 259 ns for S1-MgADP,P(i) and 271 ns for S1-MgADP at 3 degrees C in low ionic strength solutions. The data were interpreted using a hydrodynamic model consisting of a rigid linear four-bead structure that had a point at the center of one of the inner beads about which the structure can bend. The structure of S1-MgADP was approximated by adjusting the bend angle to 20 degrees. The best fit to the S1-MgADP,P(i) decay time was then obtained when the angle was increased to 38 degrees. The results obtained using this simple model suggest that MgATP binding and hydrolysis changes the structure of S1 so that one end of it moves by at least 3.9 nm. The reverse of this process, during product release, would provide a displacement large enough to account for most of the ATP-driven filament sliding that occurs in muscle or in in vitro motility assays. PMID- 8448106 TI - 5-hydroxytryptophan as a new intrinsic probe for investigating protein-DNA interactions by analytical ultracentrifugation. Study of the effect of DNA on self-assembly of the bacteriophage lambda cI repressor. AB - Pairwise cooperativity between proteins bound to DNA is believed to be important in governing the transcriptional regulation of numerous genes. However, the spectral overlap of normal proteins and DNA has blocked the study of these interactions by many physical methods. As shown recently by Ross et al. (in press), lambda cI repressor spectrally enhanced by 5-hydroxytryptophan (5-OHTrp), expressed in vivo using an Escherichia coli tryptophan auxotroph, exhibits dimer formation and DNA binding properties identical with those of the wild-type repressor. Moreover, the 5-OHTrp provides a spectral signal that allows monitoring of the protein concentration without interference from DNA. In this article, the ability to selectively detect 5-OHTrp-labeled repressor during analytical ultracentrifugation is used to study the higher order assembly of repressor dimers in the absence and in the presence of operator DNA. Contrary to the expectation that tetramer might be the limiting oligomer, lambda cI repressor undergoes a definite association to octamer. The relatively narrow concentration range over which transition from predominantly dimer to predominantly octamer occurs makes it unlikely that significant levels of tetramer are formed in the absence of DNA. Moreover, mass measurements reveal that an OR1 oligonucleotide binds to octameric repressor and does not dissociate it to tetramers. The use of the 5-OHTrp spectral enhancement opens a promising new avenue for the exploration of protein-protein and protein-nucleic acid interactions by analytical ultracentrifugation. PMID- 8448107 TI - Structural characterization of an N-acetyl-2-aminofluorene (AAF) modified DNA oligomer by NMR, energy minimization, and molecular dynamics. AB - An N-acetyl-2-aminofluorene (AAF) modified deoxyoligonucleotide duplex, d(C1-C2 A3-C4-[AAF-G5]-C6-A7-C8-C9).d(G10-G11-T12-G13-C14-++ +G15-T16-G17-G18), was studied by one- and two-dimensional NMR spectroscopy. Eight of the nine complementary nucleotides form Watson-Crick base pairs, as shown by NOEs between the guanine imino proton and cytosine amino protons for G.C base pairs or by an NOE between the thymine imino proton and adenine H2 proton for A.T base pairs. The AAF-G5 and C14 bases show no evidence of complementary hydrogen bond formation to each other. The AAF-G5 base adopts a syn conformation, as indicated by NOEs between the G5 imino proton and the A3-H3' and A3-H2'/H2" protons and by NOEs between the fluorene-H1 proton of AAF and the G5-H1' or C6-H1' proton. The NOEs from the C4-H6 proton to C4 sugar protons are weak, and thus the glycosidic torsion angle in this nucleotide is not well defined by these NMR data. The remaining bases are in the anti conformation, as depicted by the relative magnitude of the H8/H6 to H2' NOEs when compared to the H8/H6 to H1' NOEs. The three base pairs on each end of the duplex exhibit NOEs characteristic of right handed B-form DNA. Distance restraints obtained from NOESY data recorded at 32 degrees C using a 100-ms mixing time were used in conformational searches by molecular mechanics energy minimization studies. The final, unrestrained, minimum energy conformation was then used as input for an unrestrained molecular dynamics simulation. Chemical exchange cross peaks are observed, and thus the AAF-9-mer exists in more than a single conformation on the NMR time scale. The NMR data, however, indicate the presence of a predominant conformation (> or = 70%). The structure of the predominant conformation of the AAF-9-mer shows stacking of the fluorene moiety on an adjacent base pair, exhibiting features of the base displacement [Grunberger, D., Nelson, J. H., et al. (1970) Proc. Natl. Acad. Sci. U.S.A. 66, 488-494] and insertion-denaturation models [Fuchs, R.P.P., & Daune, M. (1971) FEBS Lett. 14, 206-208], while the distal ring of the fluorene moiety protrudes into the minor groove. PMID- 8448109 TI - Accommodation of insertions in helices: the mutation in hemoglobin Catonsville (Pro 37 alpha-Glu-Thr 38 alpha) generates a 3(10)-->alpha bulge. AB - Hemoglobin Catonsville is a mutation of human hemoglobin (an alpha 2 beta 2 tetramer) in which a glutamate residue is inserted into the first turn of a highly conserved 3(10) helix (the C helix) of each alpha subunit. In theory, amino acid insertions (or deletions) in protein helices can be accommodated via two distinct mechanisms. One, termed the register shift mechanism, preserves the geometry of the helix while requiring all of the residues on one flank of the insertion site to rotate by 100 degrees in the case of an alpha helix or by 120 degrees in the case of a 3(10) helix. The other, termed the bulge (or indentation) mechanism, distorts the local geometry of the helix but does not alter the helix register. High-resolution X-ray diffraction analysis of deoxyhemoglobin Catonsville shows that the inserted residue is accommodated as a bulge, demonstrating that this is a viable mechanism. (In contrast, no such evidence is yet available for the register shift mechanism.) More specifically, the insertion converts one turn of the C helix from 3(10) geometry to alpha helix like geometry, raising the possibility that a common mechanism for accommodating insertions and deletions within helices may involve localized interconversions between 3(10), alpha, and pi helical structures. PMID- 8448108 TI - Solution structure of a complex between [N-MeCys3,N-MeCys7]TANDEM and [d(GATATC)]2. AB - [N-MeCys3,N-MeCys7]TANDEM (CysMeTANDEM) is an octadepsipeptide quinoxaline antibiotic that binds specifically by bisintercalation to double-stranded DNA at NTAN sites [Addess, K. J., Gilbert, D. E., Olsen, R. K., & Feigon, J. (1992) Biochemistry 31, 339-350; Addess, K. J., Gilbert, D. E., & Feigon, J. (1992) in Structure and Function Volume 1: Nucleic Acids (Sarma, R. H., & Sarma, M. H., Eds.) pp 147-164, Adenine Press, Schenectady, NY]. We have determined the three dimensional structure of a complex of CysMeTANDEM and the DNA hexamer [d(GATATC)]2 using two-dimensional 1H NMR derived NOE and dihedral bond angle constraints. This is the first structure of a TpA-specific quinoxaline antibiotic in complex with DNA. Initial structures of the complex were generated by metric matrix distance geometry followed by simulated annealing. Eight of these structures, refined by restrained molecular dynamics, energy minimization, and NOE-based relaxation matrix refinement, have an average pairwise RMSD of 1.11 A for all structures, calculated using all heavy atoms of the drug and the DNA except the terminal base pairs. CysMeTANDEM binds to and affects the structure of the DNA in a manner similar to that observed in complexes of the CpG-specific quinoxaline antibiotics triostin A and echinomycin with DNA [Ughetto, G., Wang, A. H.-J., Quigley, G. J., van der Marel, G. A., van Boom, J. H., & Rich, A. (1985) Nucleic Acids Res. 13, 2305-2323; Wang, A. H.-J., Ughetto G., Quigley, G. J., Hakoshima, T., van der Marel, G. A., van Boom, J. H., & Rich, A. (1984) Science 225, 1115-1121; Wang, A. H.-J., Ughetto, G., Quigley, G. J., & Rich, A. (1986) J. Biomol. Struct. Dyn. 4, 319-342]. The two quinoxaline rings bisintercalate on either side of the two central T.A base pairs and the peptide ring lies in the minor groove. The central A.T base pairs of the complex are underwound (average helical twist angle of approximately -10 degrees) and buckle inward by approximately 20 degrees. There are intermolecular hydrogen bonds between each of the Ala NH and the AN3 protons of the TpA binding site, analogous to those observed between Ala NH and GN3 in the crystal structures of the CpG specific complexes of echinomycin and triostin A with DNA. However, the structure of the peptide ring of CysMeTANDEM in the complex differs from that of echinomycin and triostin A.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8448110 TI - Sequence-selective binding of amiloride to DNA. AB - Nuclease footprinting techniques have been employed to investigate the interaction between the diuretic drug amiloride, a sodium channel blocker with potential therapeutic use in the treatment of cystic fibrosis, and three DNA fragments of defined sequence. Using either DNAse I or micrococcal nuclease as probes, an unusual pattern of sequence-selective recognition of DNA has been detected. Amiloride binds selectively to sites rich in adenine and thymine residues, frequently with an apparent preference for 5'-TpX-3' steps, and discriminates strongly against GC-rich sequences which are sometimes cut more readily in the presence of the drug compared to the control. A detailed comparison with the actions of known selective DNA-binding antibiotics and drugs reveals a unique pattern of binding sites, different from those of typical intercalators on the one hand and those of minor groove-binders on the other. Amiloride is believed to adopt a pH-dependent tricyclic hydrogen-bonded conformation in solution which allows it to intercalate into DNA; consistent with this belief, we find that the footprinting pattern largely disappears at pH values above the pKa. Preliminary studies with three amiloride analogues have indicated the importance of two functional groups in the recognition of DNA. The possible relevance of selective DNA binding to activity in vivo is considered. PMID- 8448111 TI - Kinetic analysis of the deamination reactions of cyclobutane dimers of thymidylyl 3',5'-2'-deoxycytidine and 2'-deoxycytidylyl-3',5'-thymidine. AB - The cyclobutane dimer photoproducts of dTpdC and dCpdT have been produced by acetophenone photosensitization and separated by reverse-phase HPLC. Each dinucleoside monophosphate was shown to produce one cis,syn isomer and two trans,syn isomers. Three of these photoproducts, namely, the cis,syn isomers of dTpdC and dCpdT and one trans,syn isomer (the syn-anti glycosidic isomer) of dTpdC were selected to study the deamination kinetics. Analysis of the pH dependence indicates that the deamination proceeds by the hydrolysis of the imido amide group of the 5,6-saturated cytosine base with the formation of a carbinolamine intermediate. Determination of the kinetic parameters showed that, for these three cyclobutane dimers, the rate-determining step at physiological pH is a cyclobutane dimers, the rate-determining step at physiological pH is a nucleophilic attack of hydroxide ion on the protonated 5,6-saturated cytosine base. The kinetic analysis showed that the cis,syn isomers deaminate approximately 3 times faster than the trans,syn isomer, which is due to a large difference in pKa of the 5,6-saturated cytosine moiety. An electrostatic interaction between the iminium group of cytosine and the carbonyl group of thymine is proposed to account for the increase in pKa for the cis,syn isomers relative to the trans,syn isomer. A similar interaction is proposed to explain the relative difference in reactivity between the cis,syn isomers and the trans,syn isomer with regard to the breakdown of the carbinolamine intermediate. PMID- 8448112 TI - Effect of proline mutations on the stability and kinetics of folding of staphylococcal nuclease. AB - The role of proline in the stability and kinetics of folding of wild-type staphylococcal nuclease and its P117G, P117T, and P31A mutants was examined as a function of guanidinium thiocyanate (Gdn-SCN) concentration. Replacement of Pro 117 with Gly or Thr caused small increases in stability, whereas substitution of Pro-31 by Ala led to a small decrease in stability. The slopes of the plots of delta G against denaturant concentration (m) for the mutant proteins are significantly smaller than for the wild-type, suggesting a decrease in the solvent-accessible surface area of the denatured state relative to that of the wild-type. The rates of unfolding and refolding were monitored using tryptophan fluorescence. The kinetic traces for refolding in the presence of Gdn-SCN were triphasic for the wild-type protein and P31A but biphasic for P117G and P117T mutants. The slower phases were typically 10% of the total amplitude except in the transition region. The rates of the fastest and medium phases of the wild type were essentially unaffected by the mutations. Double-jump experiments in which the protein was unfolded in a high concentration of denaturant for a short time period and then refolded to final Gdn-SCN concentrations near the Cm revealed a fast increase in fluorescence emission corresponding to formation of the native state, followed by a slower decrease with an amplitude that varied with the guanidine concentration and time of unfolding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448113 TI - Probing functional regions in cardiac isomyosins with monoclonal antibodies. AB - Seven Mabs prepared against subfragment 1 (S1) of either bovine cardiac beta specific or rabbit fast skeletal muscle myosin were used to identify functional regions in cardiac isomyosin heavy chains. This approach was designed to improve the understanding of structure-function relationships within the myosin molecule and between alpha and beta myosin heavy chains (MHCs). We used bacterial expression of human beta myosin fragments and determined that the seven antibodies were localized within four different MHC subdomains: amino acid residues 33-37 (one beta-specific antibody), 67-84 (one alpha/beta-specific antibody), 85-106 (four alpha/beta-specific antibodies) and 215-248 (one alpha/beta-specific antibody). All epitopes were accessible on myosin and actomyosin with the same affinities. Therefore, none of these MHC epitopes were located on the interfaces between the myosin head and actin. Three antibodies reacting at three out of the four investigated epitopes enhanced acto-S1 ATPase activities but not myosin, S1, or actomyosin activities. One antibody, which was strictly beta-specific and bound to five amino acid residues near the most N terminal MHC end, substantially inhibited all myosin or S1 ATPase activities measured with or without actin. The epitope of this antibody coincides with one difference cluster observed between both cardiac MHC isoforms [McNally et al (1989) J. Mol. Biol. 210, 665-671], suggesting that this small variable MHC area could be one of the structural bases to explain observed functional differences in cardiac alpha and beta myosin isoforms. PMID- 8448114 TI - Contribution of loops and nicks to the formation of DNA dumbbells: melting behavior and ligand binding. AB - We have evaluated the thermodynamic contribution of thymine loops and nicks to the overall stability of double-helical DNA by investigating (1) the melting behavior of two unligated DNA dumbbells and their corresponding core duplexes and (2) the association of netropsin to the central core of four A.T base pairs of these molecules. Temperature-dependent UV absorption and differential scanning calorimetry techniques have been used to characterize the helix-coil transitions of all four deoxyoligonucleotide duplexes. In 10 mM NaP(i) buffer at pH 7.0, all transitions were monophasic. The dumbbells melt with transition temperatures, Tm, independent of strand concentration, while each duplex melts with transition temperature dependence on strand concentration, characteristic of mono- and bimolecular processes, respectively. The Tm's for the dumbbells correspond to those of single hairpins containing only four base pairs in the stem. We obtain dTm/d log [Na+] values of 10.9-12.5 degrees C for these molecules, which correspond to similar counterion releases and suggest helical structures with similar charge densities and helical strandedness. Standard thermodynamics profiles at 5 degrees C reveal that the favorable free energy of forming these ordered structures results from the partial compensation of favorable enthalpies with unfavorable entropies. The stabilization of the dumbbells relative to the core duplexes is enthalpic, due to extra stacking of the nearest loop thymines on the G.C base pairs at both ends of the stem.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448115 TI - Tris(phenanthroline)ruthenium(II) enantiomer interactions with DNA: mode and specificity of binding. AB - Absorbance and fluorescence methods, circular dichroism, UV melting experiments, viscosity, and competition dialysis were used to study the interaction of delta and lambda tris(phenanthroline)ruthenium(II) with DNA. The results of these studies indicated that both isomers bind to DNA by a single mode. The two isomers differ, however, in their effect on the hydrodynamic properties of DNA as measured by viscosity and, therefore, probably differ in their individual binding modes. The optical properties of the fully bound compounds differ from those of the free, but the perturbations of their visible absorbance and fluorescence emission spectra are modest when compared to changes observed for other DNA binding compounds. Binding of both isomers to DNA was found to be weak (in comparison to proven intercalators), with binding constants on the order of 10(4) M-1 determined for their binding to calf thymus DNA. A small, positive enthalpy was found for the binding of each isomer to DNA, suggesting that binding is entropically driven. Both isomers increased the melting temperature of DNA, with little quantitative difference between the two. A modest base specificity was found for each isomer, with the delta isomer preferentially binding to GC base pairs, and the lambda isomer preferentially binding to AT base pairs. Competition dialysis was used to examine the preference of delta and lambda Ru for right handed B DNA and left-handed Z DNA. Neither isomer exhibits significant selectivity for these radically different DNA secondary structures. PMID- 8448116 TI - Multiple binding modes of the single-stranded DNA binding protein from Escherichia coli as detected by tryptophan fluorescence and site-directed mutagenesis. AB - We have systematically substituted the four tryptophan residues of the single stranded DNA binding protein from Escherichia coli (EcoSSB) by polar (serine or threonine) and aromatic (tyrosine or phenylalanine) amino acids. The resulting mutants with either single amino acid exchanges or triple substitutions are all active in ssDNA binding, though in some cases with reduced affinities. Measurements of the fluorescence of the mutated EcoSSBs show that there is no interaction between the four different tryptophan residues. We analyzed the ssDNA binding of the mutant proteins by fluorescence titrations. At 0.3 M NaCl ("high salt"), all singly substituted proteins bind to poly(dT) in a manner comparable to wild-type EcoSSB, covering 65 nucleotides with 1 EcoSSB tetramer. W54S mutant protein is an exception since even at 0.3 M NaCl it covers approximately 35 nucleotides, a behavior which is typical of salt concentrations below 10 mM NaCl ("low salt"). From this observation, it is inferred that tryptophan-54 is involved in a direct interaction with the ssDNA favoring the "high-salt" binding mode. All mutant proteins lacking tryptophan-54 but possessing tryptophan-88 at "low-salt" concentrations show a nonmonotonous behavior in the fluorescence titrations. This behavior can be interpreted assuming a model of cooperative binding of EcoSSB to poly(dT) with two different binding site sizes (n approximately 27 and n approximately 33) and different binding affinities. A quantitative treatment of the problem of multiple binding modes in the interaction of a multidentate ligand with a linear polymer is applied to these titrations. PMID- 8448117 TI - Nucleotide preferences for DNA interstrand cross-linking induced by the cyclopropylpyrroloindole analogue U-77,779. AB - Using a 21-base-pair duplex oligonucleotide containing a centrally located defined cross-linkable site, we have separated by gel electrophoresis DNA interstrand cross-links (ISC) from monofunctionally alkylated DNA (MA) and investigated the sequence selectivity for DNA ISC induced by the CC-1065 analogue U-77,779 (U-77). Sequencing gel analysis shows that U-77 induces two distinct types of DNA ISC. The first distinct form of DNA ISC spans six nucleotides and links two adenine N3 positions within an A/T-rich sequence. The second distinct DNA ISC spans seven nucleotides, also linking two adenine N3 positions, with a preference for contiguous runs of adenines. Three major 6-nucleotide DNA ISC's were identified and found to occur within 5'-TAATTA-3', 5'-TAAATA-3', and 5' TAAAAA-3' sequences. The major 7-nucleotide DNA ISC was found to occur within 5' TAAAAAA-3' sequences. Within this sequence, the formation of the 7-nucleotide DNA ISC was preferred over the 6-nucleotide DNA ISC by a ratio of approximately 2:1. DNA ISC formation within adenine tracts eliminated the inherent DNA bending associated with such sequences. Further, chemical probing of each isolated DNA ISC with diethyl pyrocarbonate (A-specific) and potassium permanganate (T specific) shows that the major DNA conformational changes, such as helical distortion, were localized within the cross-linked sequence. These results suggest that a significant degree of DNA distortion may occur as a consequence of interstrand cross-linking. PMID- 8448118 TI - Human skin tryptase: kinetic characterization of its spontaneous inactivation. AB - The spontaneous loss of human tryptase hydrolytic activity was investigated. Time course studies monitoring the loss in catalytic activity were biphasic and correlated with a reduction in the concentration of catalytic sites. There was an initial rapid phase leading to greater than 85% loss in activity. The remaining activity gradually decayed toward completion over a 40-h period. The initial phase could be described as a first-order process with a t1/2 of approximately 6.0 min in 0.2 M NaCl (pH 6.8, 30 degrees C). The rate constant for this phase showed little, if any, sensitivity to changes in enzyme concentration, consistent with a first-order process, and analysis of the reaction as a function of temperature was consistent with a single rate-determining step. The rate of this process, however, showed marked sensitivity to changes in NaCl concentration and pH. Increasing the NaCl concentration as well as decreasing the pH below the pI (pH 6.3) reduced the rate of activity loss, whereas increasing the pH above pH 8.0 markedly increased the rate of activity loss. The effect of NaCl concentration and pH on the rate of activity loss suggests that the rate-limiting step governing the fast phase of the reaction involves electrostatic interactions. The presence of a fast and a slow phase in the decay process may suggest heterogeneity in the sample or the rapid formation of an inactive, but reversible, intermediate. A reversible intermediate was demonstrated when "inactivated tryptase" was incubated in the presence of heparin, and an increase in tryptase catalytic activity was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448119 TI - Purified Escherichia coli preprotein translocase catalyzes multiple cycles of precursor protein translocation. AB - Escherichia coli preprotein translocase, composed of the peripheral membrane protein SecA bound at the integral membrane domain SecY/E, has been isolated and functionally reconstituted [Brundage, L., Hendrick, J. P., Schiebel, E., Driessen, A. J. M., & Wickner, W. (1990) Cell 62, 649-657]. It is not known whether this purified enzyme supports multiple turnover cycles and how its kinetics compare with translocase in inverted membrane vesicles. We now report a quantitative comparison of the translocation of the outer membrane protein A precursor (proOmpA) by purified preprotein translocase and by inner membrane vesicles. ProOmpA cross-linked to bovine pancreatic trypsin inhibitor was used for quantitative titration of the functional translocation sites. The rate of proOmpA translocation per active site in this purified system is 25% of that observed in inverted membrane vesicles. Each functional site can catalyze multiple cycles of precursor translocation. These results indicate that the purified preprotein translocase properly reconstitutes translocation. PMID- 8448120 TI - Steric requirements at position B12 for high biological activity in insulin. AB - The alpha-helix formed by the amino acid residues 9-19 of the B-chain of insulin is involved in the stabilization of its three-dimensional structure. We have shown that modification at positions B9, B10, B12, and B16 results in analogues possessing biological activities ranging from ca. 0.2% to ca. 500% relative to that of natural insulin. The lowest potency was displayed by [B12 Asn]insulin, in which the hydrophobic B12 Val residue was replaced by the hydrophilic Asn residue. We now report the synthesis of four insulin analogues in which hydrophobicity is retained, and only the spatial arrangement of atoms in the B12 region is altered. Substitution of B12 Val with alpha-aminoisobutyric acid (Aib), D-Ala, and Phe led to analogues possessing biological activities, in lipogenesis assays, of 8.5%, 2%, and 0.2%, respectively, relative to that of natural insulin. Inversion of the B11-B12 sequence, -Leu-Val-, led to an analogue displaying 3.3% activity. A synthetic B-chain in which the B11 Leu-B12 Val sequence was replaced by B11 Ala-B12 Ile was incapable of combining with the natural A-chain. We conclude that the Val residue in the B12 position in insulin fulfills special side-chain packing requirements involved in the stability of the structure of insulin. Even slight steric alteration at position B12 results in a distortion of the overall conformation of the B-chain which affects its ability to combine with the natural A-chain. This distortion is retained in the corresponding analogue, which is reflected in diminished biological potency. PMID- 8448121 TI - Cholesterol efflux from fibroblasts to discoidal lipoproteins with apolipoprotein A-I (LpA-I) increases with particle size but cholesterol transfer from LpA-I to lipoproteins decreases with size. AB - To understand the role of different discoidal lipoproteins in cellular cholesterol efflux, defined discoidal lipoproteins containing 2, 3, or 4 apolipoproteins (apo) A-I per particle (Lp2A-I, Lp3A-I, and Lp4A-I) were prepared from mixtures of apoA-I and phospholipids with or without cholesterol. Each particle had a slow pre beta migration on agarose gel electrophoresis which further decreased as the number of apoA-I increased. Incubation of cholesterol labeled human fibroblasts with the different LpA-I at an equimolar concentration in apoA-I showed that the best acceptors of cellular cholesterol were Lp4A-I, followed by Lp3A-I and Lp2A-I. Cholesterol efflux to these particles was positively correlated to the number of apoA-I, to the ratio of phospholipids to apoA-I, and to the size of particles, three interrelated parameters. To follow the subsequent movement of cellular cholesterol after it became associated with LpA-I, cholesterol- and apoA-I-labeled LpA-I were incubated with plasma which resulted in parallel modifications of each labels electrophoretic migration with time. However, [3H]cholesterol-labeled LpA-I transferred from pre beta to alpha migration with a precursor-product relationship while 125I-LpA-I progressively shifted from pre beta to alpha migration. The change in electrophoretic migration of 125I-LpA-I is independent of cholesterol and appears related only to a modification of apoA-I charge. Lp2A-I was fastest in changing its electrophoretic migration to alpha, followed by Lp3A-I and then Lp4A-I.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448122 TI - Structure and dynamics of mucin-like glycopeptides. Examination of peptide chain expansion and peptide-carbohydrate interactions by stochastic dynamics simulations. AB - Mucins and other highly O-linked glycoproteins have been found to exist in random coil conformations with peptide chain dimensions about 3-fold more expanded than found for deglycosylated mucins or denaturated proteins. We have examined the origin of the peptide chain expansion in mucins by stochastic dynamics simulations which include a treatment of solvation energy effects based on solvent-accessible surface area and polarizability [GB/SA; Still, C. W., et al. (1990) J. Am. Chem. Soc. 112, 6127]. The glycopeptides studied contained pairs of threonine residues (flanked by alanine residues) which were O-glycosylated by the di- and monooligosaccharide side chains alpha-NeuNAc(2-6)alpha-GalNAc and alpha GalNAc. These glycopeptides serve as simple models for native and asialo ovine submaxillary mucin. Computer stochastic dynamic simulations show a significant decrease in end-to-end distance and radius of gyration (32% and 33%, respectively) upon complete removal of carbohydrate from the glycopeptide AAA(NeuNAc-(2-6)GalNAc)-T(NeuNAc(2-6)GalNAc)-TAAA. These changes are consistent with the extrapolations of the mucin chain dimension data to glycopeptides of this size. The simulations have identified two potentially strong peptide carbohydrate hydrogen bonds that can influence the orientation of O-linked GalNAc. With two contiguous glycosylated sites, the lowest energy conformation obtained is characterized by a GalNAc amide proton hydrogen bond to the carbonyl of the peptide residue C-terminal to the site of glycosylation. This conformation differs from the glycopeptide conformations predicted for glycopeptides with single or widely spaced glycosylation sites. The results suggest that the experimentally determined mucin peptide chain dimensions can be fully accounted for by short-range (+/- 3 residue) intramolecular steric and hydrogen bond interactions resulting from the clustering of glycosylated residues. PMID- 8448123 TI - Regeneration of bovine pancreatic ribonuclease A. 1. Steady-state distribution. AB - The regeneration of bovine pancreatic ribonuclease A (RNase A) from the reduced to the native form with mixtures of oxidized and reduced dithiothreitol has been studied at 25 degrees C, pH 8.0, by using a variety of current experimental techniques, including quenching the regeneration reaction with 2-aminoethyl methanethiosulfonate, fractionation of intermediates by HPLC, and analysis by both UV and disulfide-specific detection systems. The disulfide-containing protein intermediates achieve a steady-state distribution after which the native protein regenerates at a rate comparable to the rates observed previously during the regeneration of RNase A with glutathione. Equilibrium constants at 25 degrees C, pH 8.0, for the interconversion of species containing different numbers of disulfide bonds are evaluated from the concentrations in the steady-state distribution. These equilibrium constants are compared with those obtained earlier when native RNase A is regenerated with glutathione. The observed equilibrium constants (with the dithiothreitol system) for the interconversions among all intermediates are very similar once statistical factors arising from the different numbers of disulfide-containing species in each grouping are taken into account. None of the disulfide-containing intermediates has any significant enzymatic activity, in agreement with earlier conclusions that these intermediates are considerably disordered. This is in sharp contrast to disulfide containing intermediates populated during the regeneration of bovine pancreatic trypsin inhibitor, which have significant nativelike structure. PMID- 8448124 TI - Regeneration of bovine pancreatic ribonuclease A. 2. Kinetics of regeneration. AB - Analysis of the experimental data of the previous paper [Rothwarf, D. M., & Scheraga, H. A. (1993) Biochemistry (first of four papers in this issue)], using the method of Konishi et al. [Konishi, Y., Ooi, T., & Scheraga, H. A. (1981) Biochemistry 20, 3945-3955; Konishi, Y., Ooi, T., & Scheraga H. A. (1982) Biochemistry 21, 4734-4740], and a discussion of the validity of the steady-state kinetic treatment of the data analyzed here are presented. The analysis reveals that RNase A regenerates with oxidized and reduced dithiothreitol (DTTox and DTTred, respectively) through a rearrangement pathway involving one or more three disulfide species; i.e., multiple pathways could be involved. This pathway is different from that observed when RNase A is regenerated with oxidized and reduced glutathione (GSSG and GSH, respectively). These differences result primarily from the very different characteristics of the oxidation of thiols with DTTox and GSSG, respectively. In addition, the concept of multiple pathways, as applied to the regeneration of RNase A, is developed. PMID- 8448125 TI - Regeneration of bovine pancreatic ribonuclease A. 3. Dependence on the nature of the redox reagent. AB - Monothiol reagents such as oxidized and reduced glutathione (GSSG and GSH, respectively) form stable mixed disulfides with protein thiols while dithiol reagents such as oxidized and reduced dithiothreitol (DTTox and DTTred, respectively) do not. This large difference in the stabilities of the mixed disulfides is reflected in much greater rates of formation and reduction of protein disulfide bonds with GSSG/GSH than with DTTox/DTTred. With dithiothreitol, the concentrations of intermediate species in the steady state depend on the redox potential, i.e., on the [DTTox]/[DTTred] ratio, and not on the absolute concentrations of these reagents. With glutathione, the redox potential and hence the concentrations of intermediate species in the steady state depend on the [GSSG]/[GSH]2 ratio; hence, with glutathione, in contrast to dithiothreitol, the absolute values of the concentrations do affect the steady state concentrations. Consequently, the regeneration pathways of bovine pancreatic ribonuclease A depend on the nature of the redox reagent as well as the redox potential at which they are used. The use of GSSG/GSH favors multiple regeneration pathways, while the use of DTTox/DTTred favors regeneration through fewer pathways. These concepts are also illustrated by an analysis of literature data for the regeneration pathways of bovine pancreatic trypsin inhibitor. PMID- 8448126 TI - Regeneration of bovine pancreatic ribonuclease A. 4. Temperature dependence of the regeneration rate. AB - The rate of regeneration of bovine pancreatic ribonuclease A with oxidized and reduced dithiothreitol (DTTox and DTTred, respectively) decreases by a factor of 10 when the temperature is increased from 25 to 37 degrees C. The rate of regeneration of RNase A with oxidized and reduced glutathione increases slightly over that same range of temperature. This suggests that the regeneration processes with the two types of redox reagents proceed through different pathways. There is a significant change in the distribution of three-disulfide intermediates populated during regeneration with DTTox/DTTred over the range of temperature 15-37 degrees C that suggests that the three-disulfide species populated at 15 degrees C are directly involved in the major regeneration pathway observed at 25 degrees C. PMID- 8448127 TI - Role of cysteines in the activation and inactivation of brewers' yeast pyruvate decarboxylase investigated with a PDC1-PDC6 fusion protein. AB - Possible roles of the Cys side chains in the activation and inactivation mechanisms of brewers' yeast pyruvate decarboxylase were investigated by comparing the behavior of the tetrameric enzyme pdc1 containing four cysteines/subunit (positions 69, 152, 221, and 222) with that of a fusion enzyme (pdc1-6, a result of spontaneous gene fusion between PDC1 and PDC6 genes) that is 84% identical in sequence with pdc1 and has only Cys221 (the other three Cys being replaced by aliphatic side chains). The two forms of the enzyme are rather similar so far as steady-state kinetic parameters and substrate activation are considered, as tested for activation by the substrate surrogate pyruvamide. Therefore, if a cysteine is responsible for substrate activation, it must be Cys221. The inactivation of the two enzymes was tested with several inhibitors. Methylmethanethiol sulfonate, a broad spectrum sulfhydryl reagent, could substantially inactivate both enzymes, but was slightly less effective toward the fusion enzyme. (p-Nitrobenzoyl)formic acid is an excellent alternate substrate, whose decarboxylation product p-nitrobenzaldehyde inhibited both enzymes possibly at a Cys221, the only one still present in the fusion enzyme. Exposure of the fusion enzyme, just as of pdc1, to (E)-2-oxo-4-phenyl-3-butenoic acid type inhibitors/alternate substrates enabled detection of the enzyme-bound enamine intermediate at 440 nm. However, unlike pdc1, the fusion enzyme was not irreversibly inactivated by these substrates. These substrates are now known to cause inactivation of pdc1 with concomitant modification of one Cys of the four [Zeng, X.; Chung, A.; Haran, M.; Jordan, F. (1991) J. Am. Chem. Soc. 113, 5842 49].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448128 TI - Inactivation of prostaglandin endoperoxide synthase by acylating derivatives of indomethacin. AB - Derivatives of the potent antiinflammatory agent and cyclooxygenase inhibitor indomethacin were synthesized in which the carboxylic acid moiety was converted into reactive acylating agents. Indomethacin imidazole (indomethacin-IM) and indomethacin N-hydroxysuccinimide (indomethacin-NHS) inactivated both the cyclooxygenase and peroxidase activities when incubated with the apo form of purified prostaglandin endoperoxide synthase (PGH synthase) at a stoichiometry of 1:1. Treatment of the inactivated enzyme with hydroxylamine at neutral pH led to recovery of all peroxidase and about 50% of the cyclooxygenase activity. Hydroxylamine did not regenerate the cyclooxygenase activity of indomethacin inactivated protein. Reconstitution of the apoprotein with heme protected against inactivation by indomethacin-NHS. Visible spectroscopy established that indomethacin-NHS-inactivated apoenzyme had a reduced capacity to bind heme. Indomethacin-NHS also substantially protected the apoenzyme from cleavage at the trypsin-sensitive Arg277 site. Incubation of [2-14C]indomethacin-NHS with PGH synthase led to incorporation of radioactivity into the protein, but no adduct was detected by reversed-phase HPLC, suggesting it was unstable to the chromatographic conditions. Incubation of indomethacin-NHS with apoprotein followed by HPLC analysis led to the formation of greater amounts of the hydrolysis product indomethacin than did similar treatment of holoprotein. The results suggest that indomethacin-IM and indomethacin-NHS covalently and selectively label PGH synthase near the heme binding site, leading to loss of both catalytic activities of the enzyme. PMID- 8448129 TI - Deuterium kinetic isotope effect and stopped-flow kinetic studies of the quinoprotein methylamine dehydrogenase. AB - Stopped-flow kinetic studies of the reductive half-reaction of methylamine dehydrogenase from Paracoccus denitrificans yielded kinetic constants for the reversible formation of the imine intermediate formed between the substrate and the tryptophan tryptophylquinone (TTQ) prosthetic group and for the hydrogen abstraction step which occurs concomitantly with TTQ reduction. When CD3NH2 was used as a substrate, deuterium kinetic isotope effects of 4.2 and 3.8, respectively, were measured for the rate constants that correspond to the formation and dissociation of the iminoquinone intermediate. A deuterium kinetic isotope effect of 17.2 was measured for the hydrogen abstraction step. The maximum deuterium kinetic isotope effect which was measured in steady-state kinetic experiments was 3.0. These data are discussed in relation to the reaction mechanism of methylamine dehydrogenase and the similar large deuterium kinetic isotope effect for hydrogen abstraction which has been observed for another quinoprotein, plasma amine oxidase. PMID- 8448130 TI - Engineering a novel specificity in subtilisin BPN'. AB - The specificity of subtilisin BPN' toward substrates with large hydrophobic P4 residues has been improved by single amino acid replacements at positions 104 and 107. Mutations were designed to (i) increase the size of the P4 binding pocket by replacing Ile107, which is at the bottom of the S4 pocket, by Val, Ala, and Gly and (ii) lose the hydrogen bond between Tyr104 and Ser130 at the entrance of the P4 binding pocket by changing Tyr104 to Phe and thus reduce interactions between small P4 side chains and residue 104. All mutant subtilisins, except for I107V, have increased specificity for residues with large side chains at P4 compared with wild type. Using the conventional definition of specificity as the competition of different substrates for the same enzyme, the I107G mutant subtilisin has one of the largest improvements in substrate specificity reported for subtilisin so far; kcat/KM is increased > 200-fold for Phe compared with Ala as the P4 residue. Further, the activity of I107G toward its specific substrate is comparable to that of the wild-type enzyme. Surprisingly, much of the increase in specificity on mutation of Ile107-->Gly appears to result from a lesion that is transmitted through the structure and effects catalysis. The value of kcat/KM for the small substrate acetyltyrosine ethyl ester, which binds to the S1 pocket, drops by 93% on mutation of Ile107-->Gly. The lesion in subtilisin I107G is complemented, however, on binding of longer substrates that have a large hydrophobic P4 amino acid side chain that can bind in the S4 pocket. PMID- 8448131 TI - A Euglena gracilis zinc endonuclease. AB - A 26-kDa endonuclease has been purified to homogeneity from zinc-sufficient Euglena gracilis. The protein binds to single-stranded DNA with a higher affinity than to double-stranded DNA, but it exhibits nucleolytic activity toward both. Thus, it converts supercoiled plasmid pBR322 DNA into the linear form, a property characteristic of endonucleases, and it continues to act on the linearized DNA until it is completely degraded. It also hydrolyzes heat-denatured, single stranded calf thymus DNA. Moreover, at amounts below 1 microgram, it enhances RNA synthesis by RNA polymerase II, a characteristic observed with other DNases. Its addition to an in vitro transcription assay increases RNA synthesis up to 3-fold. The nuclease requires two metal components to carry out its enzymatic activities. It hydrolyzes DNA only in the presence of millimolar amounts of magnesium or micromolar quantities of other activating metal ions, such as manganese, zinc, or cobalt. However, even when optimal concentrations of Mg2+ are present, micromolar amounts of the metal-chelating agents OP and HQSA completely inhibit pBR322 digestion. Transcription enhancement is also inhibited completely by both chelators at concentrations that do not affect the intrinsic polymerase II activity. By atomic absorption spectrometry, the enzyme contains 1 g-atom of Zn/mol, which is the likely target of chelator action. The nuclease protein can also be isolated from zinc-deficient E. gracilis, but remarkably it then contains 1 mol of Cu/g-atom and no zinc.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448132 TI - Chemical structure of the hexapeptide chromophore of the Aequorea green fluorescent protein. AB - The green-fluorescent proteins (GFP) are a unique class of proteins involved in bioluminescence of many cnidaria. The GFPs serve as energy-transfer acceptors, receiving energy from either a luciferase-oxyluciferin complex or a Ca(2+) activated photoprotein, depending on the organism. Upon mechanical stimulation of the organism, GFP emits green light spectrally identical to its fluorescence emission. These highly fluorescent proteins are unique due to the nature of the covalently attached chromophore, which is composed of modified amino acid residues within the polypeptide. This report describes the characterization of the Aequorea victoria GFP chromophore which is released as a hexapeptide upon digestion of the protein with papain. The chromophore is formed upon cyclization of the residues Ser-dehydroTyr-Gly within the polypeptide. The chromophore structure proposed here differs from that described by Shimomura [(1979) FEBS Lett. 104, 220] in a number of ways. PMID- 8448133 TI - Orientation of the saccharide chains of glycolipids at the membrane surface: conformational analysis of the glucose-ceramide and the glucose-glyceride linkages using molecular mechanics (MM3). AB - Preferred conformations of the saccharide-ceramide linkage of glucosylceramides with different ceramide structures (normal and hydroxy fatty acids) were investigated by molecular mechanics (MM3) calculations and compared with conformational features obtained for glucosylglycerolipids (diacyl and dialkyl analogues). Relaxed energy map calculations with MM3 were performed for the three bonds (C1'-O1-C1-C2, torsion angles phi, psi, and theta 1) of the glucose ceramide/diglyceride linkage at different values of the dielectric constant. For the phi torsion of the glycosidic C1'-O1 bond the calculations show a strict preference for the +sc range whereas the psi/theta 1 energy surface is dependent on the structure of the lipid moiety as well as on the dielectric constant (epsilon). Calculations performed on glucosylceramide with normal and hydroxy fatty acids at epsilon = 4 (bilayer subsurface conditions) show three dominating conformers (psi/theta 1 = ap/-sc, -sc/ap, and ap/ap). The ap/-sc conformer, which represents the global energy minimum, is stabilized by polar interactions involving the amide group. The +sc rotamer of theta 1 is unfavored in sphingolipids due to a Hassel-Ottar effect involving the sphingosine O3 and O1 oxygen atoms. Comparative calculations on glycosylglycerolipid analogues (ester and ether derivatives) show a distinct preference for the ap rotamer of theta 1. An evaluation of the steric hindrance imposed by the surrounding membrane surface shows that in a bilayer arrangement the range of possible conformations for the saccharide-lipid linkage is considerably reduced. The significance of preferred conformations of the saccharide-ceramide linkage for the presentation and recognition of the saccharide chains of glycosphingolipids at the membrane surface is discussed. PMID- 8448134 TI - Recombinant human hemoglobin: modification of the polarity of the beta-heme pocket by a valine67(E11)-->threonine mutation. AB - Using the mutagenesis and a gene expression system previously described [Fronticelli et al. (1991) J. Protein Chem. 10, 495-501], we have replaced Val67E11 in the distal heme pocket of the beta-chains of hemoglobin with Thr. The valine to threonine substitution is isosteric and only modifies the polarity of the beta-heme environment. The absorption and CD spectra of the resultant mutant hemoglobin were essentially the same as that of wild-type protein, indicating that the mutation did not cause any large conformational changes and that a water molecule was not coordinated to the ferrous iron atom. Equilibrium measurements of oxygen binding to the mutant indicate a 2-fold decrease in overall affinity relative to native or wild-type human hemoglobin. Thermodynamic analyses of O2 binding curves, based either on the sequential Adair model or on the MWC two state model, indicated that the overall decrease of O2 affinity in the system was due to a lower association equilibrium constant for the intermediates of oxygenation, particularly those involved at the third ligation step. The functional characteristics of the mutant hemoglobin in either the T- or R-state were not modified greatly by the mutation; however, the Bohr effect and sensitivity to C1- were increased, suggesting a role of the intermediates of oxygenation in the modulation of these parameters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448135 TI - Titration of protein transport activity by incremental changes in signal peptide hydrophobicity. AB - A systematic series of mutants has been generated which provides a means for titrating the dependence of protein transport activity on signal peptide hydrophobicity. These mutants involve replacement of the hydrophobic core segment of the Escherichia coli alkaline phosphatase signal peptide while maintaining the natural amino- and carboxyl-terminal segments and the overall length. The new core regions vary in composition from 10:0 to 0:10 in the ratio of alanine to leucine residues. Thus, a nonfunctional polyalanine-containing signal peptide is titrated with the more hydrophobic residue, leucine. Using precursor processing to quantify transport activity, we observe a clear, nonlinear dependence on hydrophobicity. At ratios of alanine to leucine of less than or equal to 8:2, the signal peptide is essentially nonfunctional; at ratios greater than or equal to 3:7, the signal peptide functions efficiently. The midpoint is between alanine to leucine ratios of 6:4 and 5:5. Signal peptides with hydrophobicity just below the midpoint show substantial, additional precursor processing over time while the others do not. The data are consistent with a simple model involving a two-state equilibrium between the untransported and transported species and a change in the delta G of -0.85 kcal/mol for every alanine to leucine conversion. PMID- 8448136 TI - Kinetic mechanism of lecithin retinol acyl transferase. AB - Lecithin retinol acyl transferase transfers acyl groups regiospecifically from the 1-position of lecithins to all-trans-retinol (vitamin A) and similar retinoids. LRAT is essential for the biosynthesis of 11-cis-retinal, the visual pigment chromophore, and is also required for the general dietary mobilization of vitamin A. The kinetic mechanism of this enzyme is described here, KM and Vmax values were determined for the substrates dipalmitoylphosphatidylcholine (DPPC) [1.38 microM and 0.17 microM/(min-mg), respectively] and for all-trans-retinol [0.243 microM and 0.199 microM/(min-mg), respectively]. In order to distinguish between a ping-pong bi-bi mechanism and a rapid equilibrium random or ordered bi bi mechanism, the velocity of product formation as a function of one of the substrates at different fixed concentrations of the other substrate was measured. The parallel lines generated are entirely consistent with a ping-pong bi-bi mechanism in which DPPC first binds to LRAT and acylates it and rule out both simple random binding and ordered kinetic mechanisms. Further evidence for a ping pong bi-bi mechanism comes from partial exchange reaction studies which show that LRAT can catalyze acyl group interchange between two different lecithin derivatives. Finally, the ping-pong reaction was established as being ordered, using the potent and reversible dead-end inhibitor 13-desmethyl-13,14-dihydro-all trans-retinyl trifluoroacetate. This compound proved to be competitive with respect to DPPC, with a KI = 11.4 microM, and uncompetitive with respect to all trans-retinol. PMID- 8448137 TI - Use of intracellular Ca2+ stores from rat basophilic leukemia cells to study the molecular mechanism leading to quantal Ca2+ release by inositol 1,4,5 trisphosphate. AB - Quantal Ca2+ release is a novel motif for the mediation of signal transduction in which the amplitude of a biological response following multiple stepwise increases in agonist concentration is retained. The release of Ca2+ from permeabilized cells in response to the second messenger inositol 1,4,5 trisphosphate (InsP3) proceeds in this fashion. The mechanisms leading to quantal Ca2+ release are unknown. InsP3 releases 50-90% of the Ca2+ sequestered within the intracellular stores of mammalian cells permeabilized with saponin. However, preparation of microsomes results in the loss of this sensitivity. In this report, functionally intact intracellular Ca2+ stores were isolated from rat basophilic leukemia (RBL) cells by osmotic lysis followed by differential and sucrose density gradient centrifugation. From this preparation, 64% of the stored Ca2+ is released by InsP3. We demonstrate that quantal Ca2+ release is retained by isolated Ca2+ stores and is identical to that observed in permeabilized cells. Addition of a subsaturating (28 nM) concentration of InsP3 to permeabilized cells at 37 degrees C results in the release of only a small fraction of the sequestered Ca2+. When the cells are cooled to 11 degrees C, the remaining Ca2+ is rapidly released. Hence, the mechanism leading to the quantal nature of Ca2+ release is reversible and is thus not likely to be the result of a covalent modification of the channel protein or of the Ca2+ store.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448138 TI - Kinetic stabilization of microtubule dynamic instability in vitro by vinblastine. AB - The antiproliferative action of vinblastine at low concentrations appears to result from modulation of the polymerization dynamics of spindle microtubules rather than from depolarization of the microtubules [Jordan, M. A., Thrower, D., & Wilson, L. (1991) Cancer Res. 51, 2212-2222; (1992) J. Cell. Sci. 102, 401 416]. In the present study, we used differential interference contrast video microscopy to analyze the effects of vinblastine on the growing and shortening dynamics (dynamic instability) of individual bovine brain microtubules in vitro. With microtubules which were either depleted of microtubule-associated proteins (MAPs) or rich in MAPs, low concentrations of vinblastine (0.2 microM-1 microM) suppressed the growing and shortening rates and increased the percentage of time that the microtubules spent a state of attenuated activity, neither growing nor shortening detectably. Vinblastine also suppressed the duration of microtubule growing and shortening, and increased the duration of the attenuated state, during which the microtubules neither grew nor shortened detectably. Consistent with previous data obtained using radiolabeled nucleotide exchange in microtubule suspensions [Jordan, M. A., & Wilson, L. (1990) Biochemistry 29, 2730-2739], vinblastine suppressed growing and shortening dynamics at the kinetically more rapid plus ends. The results suggest that vinblastine kinetically stabilizes microtubule ends by modulating the gain and loss of the stabilizing GTP or GDP-Pi "cap", which is believed to be responsible for the transitions between the growing and shortening phases. The data support the hypothesis that (1) low concentrations of vinblastine inhibit mitosis by kinetically stabilizing the polymerization dynamics of spindle microtubules and that (2) the dynamics of spindle microtubules are critical for the proper progression of mitosis. PMID- 8448139 TI - Phosphomannose isomerase from Saccharomyces cerevisiae contains two inhibitory metal ion binding sites. AB - Phosphomannose isomerase (PMI) from Saccharomyces cerevisiae is a zinc-dependent metalloenzyme. Besides its role in catalysis, zinc is also a potent inhibitor of the enzyme. The inhibition is competitive with the substrate mannose 6-phosphate, with Kis = 6.4 microM in 50 mM Tris-HCl buffer, pH 8.0, at 37 degrees C. This inhibition constant is 4 orders of magnitude smaller than for group II divalent cations, indicating that the binding is not primarily electrostatic. Micromolar inhibition is also observed with ions of the other metals of the electronic configuration d10. Under identical conditions, cadmium is a predominantly competitive inhibitor with Kis = 19.5 microM. Inhibition by mercury is predominantly competitive with Kis = 6.0 microM but shows a hyperbolic Dixon plot. Theorell-Yonetani double-inhibition analysis shows that zinc and cadmium ions are mutually exclusive inhibitors against mannose 6-phosphate. However, analysis of zinc and mercury double inhibition shows that they can simultaneously bind in the mannose 6-phosphate binding pocket, with only a small mutual repulsion. Inhibition of the enzyme by cadmium and zinc ions is strongly pH dependent with pKa = 9.2 for cadmium and one pKa at 6.6 and two at 8.9 for zinc. The inhibitory species are the monohydroxide forms, Zn(OH)+ and Cd(OH)+. However, inhibition by mercury is relatively pH-independent, consistent with the neutral Hg(OH)2 being the inhibitory species. In all three cases, the metal ion binding causes a conformational change in the enzyme as judged by tryptophan fluorescence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448140 TI - Heme-CO religation in photolyzed hemoglobin: a time-resolved Raman study of the Fe-CO stretching mode. AB - Time-resolved resonance Raman spectroscopy has been employed to monitor geminate heme-CO rebinding in photolyzed HbCO. The excitation frequency was tuned to enhance the scattering from rebound heme sites 20-500 ns subsequent to CO photolysis. The behavior of vFe-C during ligand rebinding has important ramifications concerning heme pocket dynamics of the distinct equilibrium configurations of the six-coordinate heme sites. During the geminate phase of recombination, the Fe-CO bond strengths and configurations of the rebound sites (inferred from the positions and line widths of vFe-C) were found to be the same as those of equilibrium configurations of HbCO within 500 ns of CO photolysis for all samples. No evidence was found for the existence of transient metastable configurations during geminate recombination. Spectra obtained at earlier times (100 ns) revealed small differences in the geminate rebinding rates of the two equilibrium configurations. Since there is little or no further CO rebinding between 100 and 500 ns after photolysis, some interconversion must occur between the dominant HbCO configurations on a submicrosecond time scale. PMID- 8448141 TI - Kinetics and mechanism of the peroxidase-catalyzed iodination of tyrosine. AB - The kinetics of iodination of tyrosine by hydrogen peroxide and iodide, catalyzed by both horseradish peroxidase (HRP) and lactoperoxidase (LPO), were studied. The initial rates of formation of both molecular I2 and monoiodotyrosine (MIT) were measured with stopped flow techniques. The following reactions occur in both systems. Enzymatic: FeIII + H2O2-->Fev = O + H2O; Fev = O + I(-)-->FeIII-O-I-; FeIII-O-I- + H(+)-->FeIII + HOI; FeIII-O-I- + I- + H(+)-->FeIII + I2 + HO-. Iodine equilibria: I2 + I-<-->I3-; I2 + H2O<-->HOI + I- + H+. Nonenzymatic iodination, one or both of the following: Tyr + HOI-->MIT + H2O; Tyr + I2-->MIT + I- + H+, where FeIII is native peroxidase, Fev = O is compound I and Tyr is tyrosine. The big difference in the two systems is that the following reaction also occurs with LPO: FeIII-O-I- + Tyr-->MIT + FeIII + HO-, which is the dominant mechanism of iodination for the mammalian enzyme. The overall rate of formation of MIT is about 10 times faster for LPO compared to HRP under comparable conditions. A small decrease in rate occurs when D-tyrosine is substituted for L tyrosine in the LPO reaction. Thus LPO has a tyrosine binding site near the heme. A kinetically controlled maximum is observed in I3- concentration. Once equilibrium is established, I2 is the dominant form of inorganic iodine in solution. However, hypoiodous acid may be the inorganic iodination reagent. PMID- 8448142 TI - Bacteriorhodopsin D85N: three spectroscopic species in equilibrium. AB - Ground-state absorbance measurements show that BR from Halobacterium halobium containing asparagine at residue 85 (D85N) exists as three distinct chromophoric states in equilibrium. In the pH range 6-12 the absorbance spectra of the three states are demonstrated to be similar to flash-induced spectral intermediates which comprise the latter portion of the wild-type BR photocycle. One of the states absorbs maximally at 405 nm, has a deprotonated Schiff base, and contains predominantly the 13-cis form of retinal, identifying it as a close homologue of the M intermediate in the BR photocycle. The other species possess absorbance maxima with correspondence to those of the wild-type N (570 nm) and O (615 nm) photointermediates. The retinal composition of the O-like form was found to be dominated by all-trans isomer. The pH dependence of the concentrations of the equilibrium species corresponds closely with the pH dependence of the M, N, and O photointermediates. These data support kinetic models which emphasize the role of back-reactions during the photocycle of bacteriorhodopsin. Energetic and spectral characterization of the D85N ground-state equilibrium supports its use as a model for elucidating molecular transitions comprising the latter portion of the BR photocycle. PMID- 8448143 TI - Expression of a cocaine-sensitive norepinephrine transporter in the human placental syncytiotrophoblast. AB - Maternal-facing brush border membrane vesicles isolated from normal term human placentas were found to accumulate norepinephrine in a concentrative manner in the presence of an inwardly directed NaCl gradient. Both Na+ and Cl- were obligatory for maximal uptake. The NaCl-dependent norepinephrine uptake was further stimulated by the presence of K+ or an acidic pH in the intravesicular medium. The uptake process was electrogenic, being stimulated by an inside negative membrane potential, and this characteristic was observed in the absence as well as in the presence of K+ inside the vesicles. Kinetic analyses revealed that one Na+ and one Cl- were involved per transport of one norepinephrine molecule. The apparent Michaelis-Menten constant for norepinephrine was 104 +/- 5nM. The uptake process exhibited higher affinity for dopamine than for norepinephrine but had low affinity for serotonin and histamine. The uptake of norepinephrine was inhibited very effectively by nomifensine, desipramine, imipramine, and cocaine, but much less effectively by bupropion and GBR 12909. Northern blot analysis with the cDNA of the human (SK-N-SH cell) norepinephrine transporter as the probe revealed that the human placenta contained two mRNAs, 5.8 and 3.6 kb in size, which hybridized to the probe. The JAR human placental choriocarcinoma cells were found unable to accumulate norepinephrine in a NaCl dependent manner. These cells were also found not to contain mRNAs which hybridized to the norepinephrine cDNA probe in northern blot. It is concluded that the human placental syncytiotrophoblast expresses a cocaine-sensitive norepinephrine transporter and that these findings may be directly relevant and important to the clinical complications of maternal cocaine abuse during pregnancy. PMID- 8448144 TI - Assembly of the Arc repressor-operator complex: cooperative interactions between DNA-bound dimers. AB - Arc repressor, a member of the beta-ribbon family of DNA binding proteins, binds to its 21-base-pair operator as a tetramer. Here, the Arc dimer is shown to bind specifically to DNA fragments containing operator half-sites, and the equilibrium and kinetic constants for these reactions are determined. DNA-bound dimers are also shown to be transient intermediates in association experiments, indicating that assembly of the Arc tetramer-operator complex occurs by sequential addition of dimers to operator half-sites. When the left or right operator half-site is occupied by an Arc dimer, cooperative interactions increase the affinity of the second dimer by approximately 5900-fold [delta delta G = -5.1 (+/- 0.5) kcal/mol]. This increase in affinity is largely caused by an increase in the half life of the complex; "non-cooperatively" bound dimers dissociate with a half-life of a few seconds while "cooperatively" bound dimers have half-lives of more than 1 h. PMID- 8448145 TI - Orientation isomers of the mitomycin C interstrand cross-link in non-self complementary DNA. Differential effect of the two isomers on restriction endonuclease cleavage at a nearby site. AB - Reductively activated mitomycin C (MC) forms DNA interstrand cross-links between two guanines at CG.CG sequences. It is predictable that such cross-links should occur in two isomeric strand orientations in duplex DNA (except when located in the center of a self-complementary duplex). This was verified by the isolation and characterization of a pair of two isomeric oligonucleotides in each case of five non-self-complementary duplexes of 8-bp length, cross-linked by MC. Isomer separation was accomplished by reverse-phase HPLC. The isomers in a pair were formed in approximately 1:1 proportion. Their structures were rigorously characterized by a two-step cross-linking procedure: first, 1''-monoalkylation of each strand, followed by conversion to a cross-linked duplex by annealing the monoalkylated strand to its complement in the presence of a reducing agent. The resulting individual authentic orientation isomers were used as standards for identification of the two isomers formed in the original (one-step) cross-linking reactions. A 16-bp duplex oligonucleotide was synthesized featuring the AluI cognate sequence, separated from a MC cross-link site by only 1 bp. Its two MC cross-linked isomers were prepared separately, and their rate of cleavage by AluI was determined using HPLC. Cleavage of both the unmodified and cross-linked duplexes was nonsymmetrical. The isomer in which the 2''-NH3+ of MC is oriented toward the AluI site was cleaved essentially at the same rate as the control duplex, while cleavage of the isomer with the MC indoloquinone group oriented toward the AluI site was inhibited 2-fold at the faster-cleaved strand.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448146 TI - Structure of the B-DNA decamer C-C-A-A-C-I-T-T-G-G in two different space groups: conformational flexibility of B-DNA. AB - For the first time, the same B-DNA oligomer has been crystallized and its structure solved in two different space groups. Crystallization of C-C-A-A-C-I-T T-G-G with Ca2+ yields monoclinic space group C2 with a = 31.87 A, b = 25.69 A, c = 34.21 A, beta = 114.1 degrees, and five base pairs per asymmetric unit. The 5026 2 sigma data to 1.3 A refine to R = 0.152 with 72 waters, one heptavalent hydrated calcium complex, and one cacodylate ion per asymmetric unit. In contrast, crystallization with Mg2+ yields trigonal space group P3(2)21 with a = b = 33.23 A, c = 94.77 A, gamma = 120 degrees, and 10 base pairs per asymmetric unit. The 1725 2 sigma data to 2.2 A refine to R = 0.164 with 36 water molecules and one octahedral magnesium complex per asymmetric unit. The monoclinic form is virtually isostructural with previously solved monoclinic decamers, including twist angles of ca. 50 degrees at C-A and T-G steps. In contrast, the trigonal structure has quite different local helix parameters, with twist angles of ca. 36 degrees at the corresponding steps. These local parameter differences can only be attributed to crystal packing, suggesting that certain sequences of B-DNA are more flexible and influenced by their surroundings than had previously been thought. Such deformability may be important for interaction of B-DNA with control proteins, where both static structure and dynamic deformability comprise components of the recognition process. The crossing of two helices at an angle of 120 degrees in the trigonal cell is a model for an antiparallel, uncrossed Holliday junction, as has been noted earlier by Timsit and Moras [Timsit, Y., & Moras, D. (1991) J. Mol. Biol. 221, 919-940] from a rhombohedral DNA dodecamer structure analysis. PMID- 8448147 TI - A DNA aptamer which binds to and inhibits thrombin exhibits a new structural motif for DNA. AB - The investigation of the three-dimensional structure of the DNA aptamer d(G1G2T3 T4G5G6T7G8T9G10G11T12T13G14G15) which binds to and inhibits thrombin has been carried out by NMR methods. This DNA exhibits a number of long-range NOEs between residues which are not adjacent in sequence, which allowed the determination of the novel tertiary structure adopted. This DNA adopts a highly compact, highly symmetrical structure which consists of two tetrads of guanosine base pairs and three loops. The residues of the tetrads alternate anti-syn-anti-syn. This novel structural motif for DNA may also be relevant to the structure of telomere DNA. PMID- 8448148 TI - Substrate specificity of 6-deoxyerythronolide B hydroxylase, a bacterial cytochrome P450 of erythromycin A biosynthesis. AB - The 6-deoxyerythronolide B hydroxylase (EryF) is a soluble cytochrome P450 responsible for the stereospecific C-6 hydroxylation of the erythromycin precursor, 6-deoxyerythronolide B. Using the expression of the eryF gene in Escherichia coli [Andersen, J. F., & Hutchinson, C. R. (1992) J. Bacteriol. 174, 725-735] as the enzyme source, we examined the catalytic activity of the EryF protein toward several macrolide substrates related to 6-deoxyerythronolide B. The results of these studies were compared with measurements of the apparent dissociation constants for various substrates and with information from molecular modeling studies of the substrates and the enzyme-substrate complex. Only minor changes in the structure of 6-deoxyerythronolide B resulted in substrates with catalytic rates less than 1% of those seen with the natural substrate. Although the 9S epimer of 9-deoxo-9-hydroxy-6-deoxyerythronolide B was hydroxylated at a rate approximately equal to the natural substrate, the 9R epimer was hydroxylated at a 2-fold lower rate. Examination of molecular models revealed that the position of the 9-hydroxyl oxygen in the 9S epimer resembles that of the 9-oxo oxygen in the natural substrate more closely than in the 9R epimer. 8,8a Deoxyoleandolide, which is identical to 6-deoxyerythronolide B except for the presence of a C-13 methyl group, and its (9S)-9-deoxo-9-hydroxy derivative were C 6 hydroxylated at a 4-fold lower rate than the natural substrate, and the 9-oxo form showed a substantially larger apparent dissociation constant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448149 TI - Structure of an engineered, metal-actuated switch in trypsin. AB - The X-ray crystal structure of the copper complex of the rat trypsin mutant Arg96 to His96 (trypsin R96H) has been determined in order to ascertain the nature of the engineered metal-binding site and to understand the structural basis for the metal-induced enzymatic inhibition. In the structure, the catalytically essential His57 residue is reoriented out of the active-site pocket and forms a chelating, metal-binding site with residue His96. The copper is bound to the N epsilon 2 atoms of both histidine residues with Cu-N epsilon 2 = 2.2 A and N epsilon 2-Cu-N epsilon 2 = 89 degrees. The metal is clearly bound to a third ligand leading to a distorted square planar geometry at Cu. The X-ray results do not unambiguously yield the identity of this third ligand, but chemical data suggest that it is a deprotonated, chelating Tris molecule which was used as a carrier to solubilize the copper in alkaline solution (pH 8.0). Upon reorientation of His57, a unique water molecule moves into the active site and engages in hydrogen-bonding with Asp102-O delta 2 and His57-N delta 1. Except for small movements of the peptide backbone near His96, the remainder of the trypsin molecule is isostructural with the native enzyme. These data support the notion that the effective inhibition of catalytic activity by metal ions observed in trypsin R96H is indeed caused by a specific and reversible reorganization of the active site in the enzyme. PMID- 8448150 TI - Pre-steady-state kinetics reveal a slow isomerization of the enzyme-NAD complex in the NAD-malic enzyme reaction. AB - Stopped-flow experiments obtained in the pre-steady-state time scale of the NAD malic enzyme reaction exhibit a lag prior to the attainment of steady state. Previous results from isotope effect studies in which the deuterium isotope effect on Vmax decreases to a value of 1 at low pH have been interpreted as suggesting a slow release of NADH [Kiick, D. M., Harris, B. G., & Cook, P. F. (1986) Biochemistry 25, 227-236]. The latter, however, requires a burst in the pre-steady-state time course, and thus the previous data have been reinterpreted in view of the observed lag. Preincubation with NAD and/or Mg increases the lag rate, with the latter having the greater effect, while preincubation with Mg and malate (or a malate analog) eliminates the lag. Data suggest a slow isomerization of E:NAD that is increased by addition of malate prior to NAD in the presence of Mg. The lag is also eliminated at low pH as a result of the overall rate being limited by the isomerization; that is, the isomerization is pH-dependent. Fumarate, an activator of the NAD-malic enzyme, when preincubated with enzyme also eliminates the lag, suggesting that the activator preferentially binds the isomerized form of the enzyme or increases the isomerization rate, or both. Stopped-flow data are corroborated by circular dichroism experiments. The unliganded enzyme is approximately 50% alpha-helix on the basis of secondary structural analysis. Binding of NAD and Mg exhibits a substantial change, with a further change observed upon binding the malate analog tartronate. PMID- 8448151 TI - Mitochondrial NADH:ubiquinone oxidoreductase (complex I): proximity of the subunits of the flavoprotein and the iron-sulfur protein subcomplexes. AB - The proximities of the three subunits (51, 24, and 9 kDa) of the flavoprotein subcomplex (FP) and five subunits (75, 49, 30, 18, and 13) of the iron-sulfur protein subcomplex (IP) of the bovine NADH: ubiquinone oxidoreductase (complex I) were investigated by cross-linking studies. The cross-linking reagents used were disuccinimidyl tartrate and ethylene glycol bis(succinimidyl succinate). The cross-linked products were identified by sodium dodecyl sulfate gel electrophoresis and immunoblotting with antibodies specific for each subunit. Results showed that the three FP subunits are juxtaposed to one another, and only the 51 kDa subunit of FP is in close proximity to only the 75-kDa subunit of IP. The 75-kDa subunit cross-linked to the 30- and the 13-kDa subunits, the 49-kDa subunit cross-linked to the 30-, 18-, and 13-kDa subunits, and the 30-kDa subunit cross-linked to the 18- and the 13-kDa subunits. No cross-linked products of 75+49-, 75+18-, or 18+13-kDa subunits were detected. These results are consistent with the occurrence of potential electron carriers in FP and IP subunits. These electron carriers are FMN and one iron-sulfur cluster in the 51-kDa subunit, one iron-sulfur cluster in the 24-kDa subunit, and apparently two iron-sulfur clusters in the 75-kDa subunit. PMID- 8448152 TI - Role of phenylalanine-327 in the closure of loop 6 of ribulosebisphosphate carboxylase/oxygenase from Rhodospirillum rubrum. AB - Phenylalanine-327 of ribulosebisphosphate carboxylase/oxygenase (rubisco) from Rhodospirillum rubrum was mutated to tryptophan, leucine, valine, alanine, and glycine, and was also deleted. The least active mutant, the deletion mutant, exhibits less than 0.5% of the carboxylase activity of the wild-type enzyme. Steady-state kinetic analysis of F327-->Leu, Val, Ala, Gly mutant enzymes reveals that kcat and the CO2/O2 specificity are unchanged while Km(RuBP) (RuBP = ribulose 1,5-bisphosphate) is drastically increased. The mutant enzyme with the highest value for Km(RuBP),Phe327-->Gly, shows a 165-fold increase (1160 microM compared to 7 microM for the wild-type). The increase in Km(RuBP) suggests an alteration of the ratio kon/koff for RuBP. A longer hydrophobic lateral chain and/or the presence of an aromatic ring in the wild-type enzyme and the Phe327- >Trp mutant enzyme could explain a better packing of loop 6 in the closed conformation and thus a tighter binding of RuBP at the active site. PMID- 8448153 TI - Low carbon monoxide affinity allene oxide synthase is the predominant cytochrome P450 in many plant tissues. AB - A cytochrome P450 with low affinity (2.9 x 10(3) M-1) for CO appears to be the major microsomal P450 in some plant tissues. The presence of low CO affinity cytochrome P450 correlates with its lack of NADPH reducibility and with the presence of high levels of 13(S)-hydroperoxy-9(Z),11(E)-octadecadienoate peroxidase activity. This activity and low CO affinity are retained by purified tulip cytochrome P450, which appears to be catalytically identical to a flaxseed derived fatty acid allene oxide synthase P450 described previously [Song, W.-C., & Brash, A.R. (1991) Science 253, 781-784]. Other heme-binding ligands, such as CN- and imidazoles, bind weakly to the allene oxide synthase P450s, suggesting that axial coordination in the heme distal pocket may be hindered. We conclude that low CO affinity is characteristic of the allene oxide synthase P450s and that these P450s constitute a major portion of the microsomal P450 in a variety of plant tissues, particularly from monocot species. PMID- 8448154 TI - Chiral recognition at cytochrome P450 1A2 active site: effects of mutations at the putative distal site on the bindings of asymmetrical axial ligands. AB - Effects of mutations at the putative distal site of cytochrome P450 1A2 on chiral discrimination for binding (R)-(+)- and (S)-(-)-1-(1-naphthyl)ethylamine (ligand I), (R)-(-)- and (S)-(+)-1-cyclohexylethylamine (ligand II), and (R)-(+)- and (S) (-)-1-(4-pyridyl)ethanol (ligand III) were studied by optical absorption spectra. The wild-type P450 1A2 exhibited different dissociation constants (Kd) for the R- and S-enantiomers of these ligands. The R/S ratios of the Kd values for ligands I and II were 5.2 and 2.9, respectively, and the S/R ratio for ligand III was 6.0. Mutations at the putative distal site, such as Glu318Asp and Glu318Ala, remarkably enhanced the discrimination: the R/S ratio of the Kd values for ligand I increased from 5.2 to 20-60, while the R/S ratio for ligand II decreased from 2.9 to 0.8-0.9. These remarkable changes in the R/S ratios were not observed with Glu318Asp mutation for ligand III binding, whereas affinities for both enantiomers of ligand III were markedly decreased by the Glu318Ala mutation. Mutation Thr319Ala increased the R/S ratio of the Kd values for ligand I slightly but markedly decreased the R/S ratio of ligand II (from 2.9 to 0.8) and the S/R ratio of ligand III (from 6.0 to 1.0). Similar enhancements of the chiral discriminations were observed with the mutation Lys250Leu at another putative substrate-recognition site. Differences between the R- and S-enantiomers of the standard enthalpy and entropy of ligand III binding were changed most remarkably by the Thr319Ser mutation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448155 TI - Evidence that serine L223 is involved in the proton transfer pathway to QB in the photosynthetic reaction center of Rhodopseudomonas viridis. AB - In the reaction center of purple photosynthetic bacteria, the reducing equivalents produced by primary charge separation are exported via an ubiquinone molecule working as a two-electron shuttle. This loosely-bound quinone, called QB, accepts in successive flashes two electrons from the tightly bound primary quinone acceptor QA, along with two protons from the external medium. The surrounding protein plays an important role in stabilizing the semiquinone anion and in providing a pathway for protons from the cytoplasmic phase to QB. Herbicides of the triazine type compete with QB for the binding pocket and their binding is controlled by nearby amino acid residues. We have studied the kinetics of the first and second electron transfer from QA to QB in two herbicide resistant mutants from Rhodopseudomonas viridis, T1 (ArgL217-->His,Ser L223- >Ala) and MAV5 (Arg L217-->His, Val L220-->Leu), in order to determine whether these residues are involved in proton transfer to the reduced QB. The main effect of the mutant T1 was a drastic (600-fold at pH 7) decrease in the rate of the second electron transfer to QB compared to the wild type. In contrast, the rate of the second electron transfer in the mutant MAV5 was decreased only slightly (10-fold) in the pH range from 7 to 11. We attribute the inhibition of the second electron transfer in the Ser L223-->Ala mutation to an essential role of Ser L223 in the donation of the first proton to the reduced QB.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448156 TI - Intrinsic tryptophan fluorescence of rat liver elongation factor eEF-2 to monitor the interaction with guanylic and adenylic nucleotides and related conformational changes. AB - Elongation factor 2 (eEF-2), which contains seven Trp residues, exhibited a tryptophan-characteristic intrinsic fluorescence with maximum excitation at 280 nm and an emission peak centered at 333 nm that suggested a hydrophobic environment of these tryptophans. Upon denaturation with 6 M guanidine hydrochloride, the maximum emission was shifted to 348 nm. Fluorescence quenching studies using acrylamide and iodide confirmed that the Trp residues were mainly buried in the native molecule and indicated an important heterogeneity, the fractional accessible fluorescence (fa) values being 0.50 and 0.25, respectively. Partial quenching of eEF-2 fluorescence by nucleotides proved the existence of an interaction of the factor in the absence of ribosomes, not only with GDP but also with GTP, nonhydrolyzable analogs, GMP, and adenylic, but not cytidylic, nucleotides. Saturating binding plots showed different maximal changes of fluorescence depending upon the nucleotides, from 6.4% with ADP to 24.5% with GDP, and suggested the existence of more than one binding site for each nucleotide. Among all the nucleotides tested, only GTP at saturating concentration modified the fa value obtained with acrylamide (-36%). The possibility that this modification is related to a conformational change of eEF-2 induced by GTP binding is discussed. PMID- 8448157 TI - Proton transfer from Asp-96 to the bacteriorhodopsin Schiff base is caused by a decrease of the pKa of Asp-96 which follows a protein backbone conformational change. AB - In the bacteriorhodopsin photocycle the transported proton crosses the major part of the hydrophobic barrier during the M to N reaction; in this step the Schiff base near the middle of the protein is reprotonated from D96 located near the cytoplasmic surface. In the recombinant D212N protein at pH > 6, the Schiff base remains protonated throughout the photocycle [Needleman, Chang, Ni, Varo, Fornes, White, & Lanyi (1991) J. Biol. Chem. 266, 11478-11484]. Time-resolved difference spectra in the visible and infrared are described by the kinetic scheme BR- >K<==>L<==>N (-->N')-->BR. As evidenced by the large negative 1742-cm-1 band of the COOH group of the carboxylic acid, deprotonation of D96 in the N state takes place in spite of the absence of the unprotonated Schiff base acceptor group of the M intermediate. Instead of internal proton transfer to the Schiff base, the proton is released to the bulk, and can be detected with the indicator dye pyranine during the accumulation of N'. The D212N/D96N protein has a similar photocycle, but no proton is released. As in wild-type, deprotonation of D96 in the N state is accompanied by a protein backbone conformational change indicated by characteristic amide I and II bands. In D212N the residue D96 can thus deprotonate independent of the Schiff base, but perhaps dependent on the detected protein conformational change. This could occur through increased charge interaction between D96 and R227 and/or increased hydration near D96. We suggest that the proton transfer from D96 to the Schiff base in the wild-type photocycle is driven also by such a decrease in the pKa of D96. PMID- 8448158 TI - Structural studies of the scrapie prion protein using mass spectrometry and amino acid sequencing. AB - The only component of the infectious scrapie prion identified to date is a protein designated PrPSc. A posttranslational process converts the cellular PrP isoform (PrPC) into PrPSc. Denatured PrPSc was digested with endoproteases, and the resulting fragments were isolated by HPLC. By both mass spectrometry and Edman sequencing, the primary structure of PrPSc was found to be the same as that deduced from the PrP gene sequence, arguing that neither RNA editing nor protein splicing feature in the synthesis of PrPSc. Mass spectrometry also was used to search for posttranslational chemical modifications other than the glycosylinositol phospholipid anchor attached to the C-terminus and two Asn linked oligosaccharides already known to occur on both PrPSc and PrPC. These results contend that PrPSc molecules do not differ from PrPC at the level of an amino acid substitution or a posttranslational chemical modification; however, we cannot eliminate the possibility that a small fraction of PrPSc is modified by an as yet unidentified posttranslational process or that PrPC carries a modification that is removed in the formation of PrPSc. It seems likely that PrPSc differs from PrPC in its secondary and tertiary structure, but the possibility of a tightly bound, disease-specific molecule which purifies with PrPSc must also be considered. PMID- 8448159 TI - Structural studies of the lipooligosaccharides from Haemophilus influenzae type b strain A2. AB - The outer membrane lipooligosaccharides (LOS) from Haemophilus influenzae type b strain A2 are a heterogeneous mixture of glycolipids containing a conserved Lipid A structure and a variable oligosaccharide moiety. After O-deacylation by treatment with anhydrous hydrazine, the O-deacylated LOS mixture was analyzed by electrospray mass spectrometry and shown to contain 11 components, ranging in M(r) from 2277.8 to 3416.4. The majority of these structures contained a variable number of hexoses, three L-glycero-D-manno-heptoses, and one 3-deoxy-D-manno octulosonic acid (KDO) residue attached to a diphosphorylated O-deacylated Lipid A moiety. Additional phosphate and phosphoethanolamine (PEA) groups were also present on the oligosaccharide structures. Two minor high molecular weight components were also observed that contained N-acetylhexosamine and sialic acid. Neuraminidase treatment of the O-deacylated LOS mixture resulted in the loss of sialic acid from these latter two species. After mild acid hydrolysis and separation by size-exclusion chromatography, liquid secondary ion mass spectrometry identified six major and four minor oligosaccharides, ranging in M(r) from 1243.4 to 2215.8. These released oligosaccharides contained a common heptose trisaccharide core structure with anhydro-KDO at the reducing terminus, which arises as an artifact of the hydrolysis procedure by beta-elimination of a phosphate group from the 4-position of KDO. Selected oligosaccharide fractions were subjected to composition and methylation analyses and sequenced by tandem mass spectrometry. Taken together, these data defined the major O-deacylated LOS as follows: [formula: see text] Higher molecular weight structures in the mixture contained galactose, N-acetylglucosamine, and sialic acid as additional branch sugars, suggesting that H. influenzae A2 is capable of forming a sialylated lactosamine structure. PMID- 8448160 TI - Overexpression, purification, and mechanistic study of UDP-N acetylenolpyruvylglucosamine reductase. AB - The recently isolated Escherichia coli murB gene (Pucci et al., 1992) has been cloned into an expression vector and the encoded UDP-N acetylenolpyruvylglucosamine reductase (EC 1.1.1.158) was overproduced to about 10% of soluble cell protein. The encoded 38-kDa protein has been purified to near homogeneity. It was found to be a monomer and to contain stoichiometric amounts of bound FAD which is reducible in catalytic turnover. The enzyme utilizes the 4 pro-S hydrogen of NADPH to reduce the enolpyruvyl group of UDP-N acetylglucosamine enolpyruvate to the lactyl ether in UDP-N-acetylmuramic acid. NMR analysis of products from 2H2O and 4S-[2H]NADPH incubations establishes that a hydride from NADPH via E.FADH2 is transferred to the beta-methyl of the 3-O lactyl moiety and a proton from solvent to the alpha-carbon of the lactyl moiety of UDP-N-acetylmuramic acid. A mechanism for this unusual enolether reduction in bacterial cell wall assembly is proposed. PMID- 8448161 TI - Overall kinetic mechanism of 6-phosphogluconate dehydrogenase from Candida utilis. AB - A complete initial velocity study of the 6-phosphogluconate dehydrogenase from Candida utilis at pH 7 and 25 degrees C in both reaction directions suggests a rapid equilibrium random kinetic mechanism with dead-end E:NADP:(ribulose 5 phosphate) and E:NADPH:(6-phosphogluconate) complexes. Like substrate-product (NADP/NADPH and 6-phosphogluconate/ribulose 5-phosphate) pairs are competitive whatever the concentration of the other substrates but noncompetitive versus the other substrates, e.g., NADPH exhibits noncompetitive inhibition versus 6 phosphogluconate. This trend also holds true for all dead-end analogs, e.g., ATP ribose is competitive versus NADP and noncompetitive versus 6-phosphogluconate. A quantitative analysis of the kinetic inhibition constants supports the assignment of kinetic mechanism. The ratio of the maximum velocities in the oxidative decarboxylation and reductive carboxylation directions is 75. PMID- 8448162 TI - Chemical mechanism of 6-phosphogluconate dehydrogenase from Candida utilis from pH studies. AB - The pH dependence of kinetic parameters and dissociation constants for competitive inhibitors was determined in order to obtain information on the chemical mechanism for the 6-phosphogluconate dehydrogenase reaction from Candida utilis. A mechanism is proposed in which an active site general base accepts the proton from the 3-hydroxyl concomitant with hydride transfer at C-3; the resulting 3-keto intermediate is decarboxylated to give the enol of ribulose 5 phosphate, followed by tautomerization of the enol to the keto product with the assist of a second enzyme residue acting as a general acid. There is also a requirement for an ionized phosphate of 6-phosphogluconate and ribulose 5 phosphate for optimum binding. The maximum velocity is pH dependent, decreasing at high and low pH giving pK values of 6 and 10, while the V/K for 6 phosphogluconate decreases at low pH with a slope of 2 yielding pK values of 6.4 and 7.6, respectively, and at high pH with a slope of -1 yielding a pK of 8.2. The 6-sulfogluconate pKi profile decreases at low and high pH giving pK values of 7.1 and 8.5, respectively. The 5-phosphoarabonate and 5-phosphoarabonate pKi profiles show similar behavior giving pK values of 6.5 and 8.8, respectively, for the former and 6.8 and 8.8, respectively, for the latter. The V/K for NADP also decreases at low and high pH giving pKs of 7.5 and 8.1, while the ATP-Ribose pKi profile decreases at low and high pH giving pKs of 7.2 and 8.0.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448163 TI - Effect of cholesterol oxidase treatment on physical state of renal brush border membranes: evidence for a cholesterol pool interacting weakly with membrane lipids. AB - Treatment with cholesterol oxidases has shown that cholesterol is heterogeneously distributed in brush borders isolated from the apical membrane domain of the renal and intestinal epithelial cells [Bloj, B., & Zilversmit, D. B. (1982) J. Biol. Chem. 257, 7608-7614; El Yandouzi, E. H., & Le Grimellec, C. (1992) Biochemistry 31, 547-551]. To better understand the origin of cholesterol heterogeneity, the effects of cholesterol oxidation by Brevibacterium sp. cholesterol oxidase on the physical state of renal brush border membrane vesicles were determined using steady-state fluorescence polarization and differential phase fluorescence of 1,6-diphenyl-1,3,5-hexatriene (DPH). Selective quenching by trinitrobenzenesulfonate indicated that DPH distributes equally between outer and inner membrane leaflets. Oxidation of 90% of the cholesterol decreased the steady state anisotropy of DPH, determined at 37 degrees C, by 14%. This modification corresponded to a change in the lipid order, the rotational rate of the probe being unaffected. Oxidation of the cholesterol corresponding to the readily accessible pool (30% of the total cholesterol), on the other hand, had a very limited effect on the membrane physical state. This contrasted with the linear decrease in both anisotropy and fluorescence lifetime of DPH obtained when cholesterol was replaced by cholestenone in liposomes made of phosphatidylcholine/sterol (1/1 molar ratio). These results indicate that, in brush border membranes, the cholesterol readily accessible to cholesterol oxidase interacts only weakly with the other membrane lipids. PMID- 8448164 TI - Transfer of long-chain fluorescent fatty acids between small and large unilamellar vesicles. AB - Transfer of 12-(9-anthroyloxy)stearic acid (12AS) was measured between small unilamellar vesicles (SUV) and between large unilamellar vesicles (LUV), over a temperature range of 5-50 degrees C. The results of this study clearly establish the biexponential nature of the time dependence of the transfer in a variety of vesicle types and confirm our previous results using egg phosphatidylcholine (EPC) SUV at 25 degrees C (Storch & Kleinfeld, 1986). In our previous study we developed a kinetic model of the transfer process and concluded that the observed time dependence of the transfer of long-chain 12-(9-anthroyloxy) fatty acids (AOFA) was due to transbilayer flip-flop that was much slower than the rate at which the fatty acids (FA) move from the vesicle and into the surrounding aqueous phase (the off step). In the present study, experimental and theoretical advances have allowed us to examine, in detail, predictions of the kinetic model that critically depend upon the slow rate of flip-flop. The current results verify these predictions and demonstrate that slow AOFA flip-flop is rate limiting in at least three different vesicle systems and at all temperatures studied. Moreover, both flip-flop and the off rate constants were almost an order of magnitude smaller in EPC-LUV than in EPC-SUV. Flip-flop was found to be asymmetric (the rate constant for transfer from the inner to outer hemileaflet of the bilayer is approximately twice that from the outer to inner hemileaflet) in SUV but virtually symmetric in LUV. The temperature dependence of transfer was used to determine the thermodynamic activation potentials for the flip-flop and off rate constants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448165 TI - Cobra venom cardiotoxin (cytotoxin) isoforms and neurotoxin: comparative potency of protein kinase C inhibition and cancer cell cytotoxicity and modes of enzyme inhibition. AB - Effects of cobra cardiotoxin (cytotoxin) and its isoforms, and neurotoxin, on protein kinase C (PKC) and cancer cells were investigated. A positive correlation existed between hydrophobicities and activities of the toxins to inhibit PKC activity (assayed using phosphatidylserine vesicle, arachidonate monomer, and Triton/phosphatidylserine mixed micelle systems), phorbol ester binding to PKC, proliferation of several cancer cell lines, and phorbol ester-induced HL60 cell differentiation. Their relative hydrophobicities and activities, in a decreasing order, were cardiotoxin-1 approximately cardiotoxin-3 > cardiotoxin (a mixture of isoforms) > cardiotoxin-4 >> neurotoxin (inactive). Under the mixed micelle assay system (containing 0.3% Triton X-100, 8 mol % phosphatidylserine, 2 mol % diolein, and 200 microM CaCl2), cardiotoxin inhibited PKC competitively with respect to phosphatidylserine (apparent Ki of about 0.06 mol % or 2.5 microM), and in a mixed-type manner with respect to both diolein (apparent Ki of about 0.04 mol % or 1.7 microM) and Ca2+ (apparent Ki of about 2.9 microM). On the basis of findings that IC50 (approximately 0.3 microM) of cardiotoxin for inhibition of HL60 cell proliferation and differentiation was lower than its IC50 (9 microM) for PKC inhibition in vitro in the phosphatidylserine vesicle system and that PKC inhibition was the only known molecular mechanism of cardiotoxin, it was suggested that cardiotoxin might be highly membrane interacting and that the observed cellular effects of cardiotoxin might be mediated, in part, via PKC inhibition. PMID- 8448167 TI - Colicin Ia inserts into negatively charged membranes at low pH with a tertiary but little secondary structural change. AB - Colicin Ia, a member of the channel-forming family of colicins, inserts into model membranes in a pH- and lipid-dependent fashion. This insertion occurs with single-hit kinetics, requires negatively charged lipids in the target membrane, and increases in rate as the pH is reduced below 5.2. The low-pH requirement does not act by inducing a secondary structural change in colicin Ia, which remains 66% +/- 4% alpha-helical between pHs 7.3 and 3.1 as determined by circular dichroism. The secondary structure also remains unchanged between pHs 7.3 and 4.2 in the hydrophobic environment provided by the detergent octyl beta-D glucopyranoside (beta-OG). However, at pH 3.1 in the presence of beta-OG, an 11% +/- 3% decrease in the alpha-helical content is observed. Further, beta-OG induces a change in tryptophan fluorescence and an altered pattern of proteolytic digestion, indicative of a tertiary structural changes. This suggests that colicin Ia undergoes a tertiary but little or no secondary structural change in its transition from a soluble to a transmembrane protein. PMID- 8448166 TI - Ligand binding by a recombinant insect juvenile hormone binding protein. AB - A cDNA for the hemolymph juvenile hormone binding protein (JHBP) of larval Manduca sexta has been isolated, sequenced, and expressed in an insect cell line. A recombinant baculovirus, containing the JHBP cDNA fused to the p10 promoter of Autographa californica nuclear polyhedrosis virus, was constructed. Insect cells (Sf9) infected with this virus secreted recombinant JHBP (rJHBP) into the medium (> 50 micrograms/mL), and cotranslational removal of an 18 amino acid leader sequence was observed. rJHBP was cross-reactive with an antiserum prepared to the hemolymph JHBP and was specifically labeled by [3H]EHDA, a photoaffinity analog of JH II, demonstrating that rJHBP was an isoform of the previously reported 32 kDa JHBP [Lerro, K. A., & Prestwich, G.D. (1990) J. Biol. Chem. 265, 19800 19806]. rJHBP was purified from insect cell medium to homogeneity by ion-exchange and gel-filtration chromatography. The purified rJHBP had a higher affinity (KD = 11 nM for JH I and KD = 42 nM for JH II) than that reported for crude hemolymph JHBP (KD = 80 nM for JH I). The circular dichroism (CD) spectrum of purified rJHBP indicated 34% alpha-helix and 23% beta-sheet. The CD spectra of rJHBP in the presence and absence of JH II were the same, indicating no change in secondary structure induced by ligand binding. Thus, the rJHBP expressed in insect cells binds JHs and is suitable for structural and functional analysis. PMID- 8448168 TI - A possible family of B-like triple helix structures: comparison with the Arnott A like triple helix. AB - Recent experimental studies of the structure of triple helices show that their conformation in solution differs from the A-like structure derived from diffraction data on triple helix fibers by Arnott and co-workers. Here we show by means of molecular modeling that a family of triple helix structures may exist with similar conformational energies, but with a variety of sugar puckers. The characteristics of these putative triple helices are analyzed for three different base sequences: (T.AxT)n, (C.GxC+)n, and alternating (C.GxC+/T.AxT)n. In the case of (C.GxC+)n triple helix, infrared and Raman spectra have been obtained and clearly reveal the existence of both N- and S-type sugars in solution. The molecular mechanics calculations allow us to propose a stereochemically reasonable model for this triple helix, in good agreement with the vibrational spectroscopy results. PMID- 8448169 TI - On the metastability of left-handed DNA motifs. AB - Alternating purine-pyrimidine DNA sequences such as poly [d(C-G)] or poly[d(m5C G)] undergo a cooperative, salt-induced structural transition from a right-handed B conformation, which prevails at relatively low ionic strength, into a left handed Z form, generally believed to be stabilized by high salt concentrations. We report here that upon a monotonous increase of the ionic strength, the well established B to Z transition is followed by a second, hitherto unobserved conformational change leading from Z-DNA back into a right-handed B-like form. This observation indicates that, in contrast with the current convention, the Z motif represents an unstable configuration relative to the B form at both low and high salt concentrations and that the occurrence of a left-handed DNA structure, presently depicted as a step function of the ionic strength, should rather be treated in terms of a pulse. The reported transition underscores the inherent metastability of the Z configuration, and indicates, consequently, that this motif is ideally suited to act as a structural regulatory element, as such an element should be endowed with a large susceptibility to cellular parameters. PMID- 8448170 TI - Diepoxybutane cross-links DNA at 5'-GNC sequences. AB - Epoxides are cancer-causing agents chemically analogous to the nitrogen mustards, a family of powerful antitumor drugs. We found that the DNA interstrand cross linking sequence preference of diepoxybutane is the same as that of the mustard mechlorethamine: 5'-GNC. Therefore, the genomic site of cross-linking alone cannot explain why some interstrand cross-linkers act as antitumor agents whereas others are deadly toxins. PMID- 8448171 TI - Amino-acid sequence of the cooperative dimeric myoglobin from the radular muscles of the marine gastropod Nassa mutabilis. AB - The complete amino-acid sequence of the dimeric and cooperative myoglobin from the radular muscles of Nassa mutabilis, a common edible gastropod mollusc on the Italian coast, has been determined. The molecule is a homodimer. The monomer is composed of 147 amino-acid residues, with a molecular mass of 15,760 Da. Its sequence is homologous with those of the dimeric myoglobins of the gastropod molluscs of the Prosobranchia subclass Busycon canaliculatum (63% conserved residues) and Cerithidea rhizophorarum (46% conserved residues). The rate of autoxidation to met-myoglobin of N. mutabilis oxymyoglobin at 25 degrees C is strongly pH-dependent with relative minimal rate values in the pH range 7 to 8. PMID- 8448172 TI - Comparing the human and schistosomal hypoxanthine-guanine phosphoribosyltransferases by circular dichroism. AB - The hypoxanthine-guanine phosphoribosyltransferases (HGPRTases) of human and the parasitic trematode, Schistosoma mansoni, are of biomedical importance. The conformations of these two enzymes were studied by circular dichroism (CD). The schistosomal HGPRTase is estimated to contain 27% alpha-helix and 30% beta structure. This result is consistent with what is predicted from a tertiary model (Craig, S.P., Cohen, F.E., Yuan, L., McKerrow, J.H. and Wang, C.C. (1991) in Molecular & Immunological Aspects of Parasitism (Wang, C.C., ed.), pp. 122-138, Am. Assoc. Adv. Sci., Washington DC, USA), which proposes that the enzyme is an alpha/beta barrel protein. The human enzyme is estimated to contain 21% alpha helix and 53% beta-form. The two enzymes are different in their thermostability. The human enzyme remains active after being heated to 85 degrees C for 15 min, while the schistosomal enzyme only retains its activity at temperature below 65 degrees C. The transition temperature (T1/2) of the schistosomal HGPRTase was determined by CD measurement to be 57.5 degrees C. One of the enzyme substrates, phosphoribose pyrophosphate (PRPP), stabilizes the HGPRTases by preventing the human enzyme from unfolding at 85 degrees C and partially protecting the schistosomal enzyme from unfolding at 65 degrees C. It is suggested that the amino-acid substitutions in the human enzyme improve the spatial structure and stability of its alpha-helices, which may lead to an enhanced thermostability. PMID- 8448174 TI - Loss of poly(ADP-ribose) synthetase activity without change in arginine-specific ADP-ribosyltransferase activity by acid-treatment; application of the treatment to simple assay for transferase in the presence of poly(ADP-ribose) synthetase. AB - We investigated the effects of acid treatment (pH 3.5) on the activities of arginine-specific ADP-ribosyltransferase (mono(ADP-ribosyl)transferase) (EC 2.4.2.31) and poly(ADP-ribose) synthetase (EC 2.4.2.30) purified from chicken liver, and we observed that the former enzyme retained completely its activity while there was no evidence for activity of the latter enzyme. Kinetic parameters, including Km values for NAD and whole histones in the reaction catalyzed by acid-treated ADP-ribosyltransferase, were the same as those in the reaction catalyzed by non-treated enzyme. The stereospecificities of the reaction forming ADP-ribosylarginine by acid-treated and non-treated ADP ribosyltransferases were indistinguishable. We made use of this acid treatment to determine ADP-ribosyltransferase activity in chicken and chick-embryo liver extracts, with a filter assay. The enzyme activities (means +/- S.D. for three separate experiments) of 1-year-old chicken and 13-day-old chick embryo livers were 372.7 +/- 80.20 and 110.6 +/- 27.22 nmol ADP-ribose/g wet liver per h, respectively. This acid treatment is useful for filter assay with labelled NAD of arginine-specific ADP-ribosyltransferase in the fraction containing poly(ADP ribose) synthetase. PMID- 8448173 TI - Kinetics of the equilibration of O2 with Panulirus interruptus hemocyanin subunits a, b and c. AB - The kinetics of the equilibration (25 degrees C) of O2 with the separated a, b and c subunits of Panulirus interruptus hemocyanin (Hc) as monomer and hexamer forms, as well as the native unfractionated abc mix, have been studied at pH values in the range 6.8-9.6, I = 0.100 M (NaCl). Rate constants kon and koff defined by deoxyHc + O2 <=> oxyHc have been determined by temperature-jump and stopped-flow techniques, respectively. The aggregation of monomer forms of different subunits to give hexamer is favoured by low pH and the availability of Ca2+, traces of which (or any other 2 + metals) are effectively removed by complexing with EDTA (5 mM). With or without EDTA, the hexamer form is present at the lower pH values. At the higher pH values with EDTA present a and b but not c give monomer forms. The hexamers are however retained at the higher pH values on addition of Ca2+ (10 mM). Cooperativity is observed for the hexamer forms at pH > 8, where the existence of relaxed (R) and tense (T) forms gives rise to sigmoidal kinetic plots in the determination of koff. Subunit c is different in that it retains its hexamer structure over the whole pH range, and does not display a Bohr effect. Native unfractionated protein is present as a hexamer mix of a, b and c in non-stoichiometric amounts, which has an enhanced Bohr effect as compared to the separated subunits. PMID- 8448175 TI - Interaction of EDTA with horseradish peroxidase: 1H-NMR study. AB - Interaction of EDTA with horseradish peroxidase (HRP) was investigated by NMR relaxation-rate measurements. At pH 4.0, the apparent dissociation constant (Kd) for the EDTA binding to HRP was deduced to be 78 mM from the relaxation measurements. From pH-dependence of 1H-NMR line width of EDTA, it was observed that EDTA binds to HRP only under acidic conditions (pH < 5). The binding of EDTA to HRP was facilitated by protonation of an acid group on the enzyme with pKa 4.0. The Kd for EDTA binding to HRP was also evaluated in the presence of an excess of exogenous substrates such as iodide and thiocyanate ions. The Kd in the presence of iodide and thiocyanate ions showed that EDTA competes with these ions for the same binding site. The distance of EDTA protons from ferric centre of HRP were deduced from 1H-NMR relaxation measurements and was found to be in the order of 8 A. PMID- 8448176 TI - Purification of macaque liver flavin-containing monooxygenase: a form of the enzyme related immunochemically to an isozyme expressed selectively in adult human liver. AB - A microsomal flavin-containing monooxygenase (FMO) was purified 77-fold from macacque liver microsomes on the basis of its methyl p-tolyl sulfoxidase activity. Sequential chromatography on anion- and cation-exchangers, lauryl Sepharose and 2',5'-ADP-Sepharose provided a purified preparation which exhibited an apparent molecular mass of 59 kDa and a pI of 8.3. N-terminal amino-acid sequencing revealed the characteristic Gly-X-Gly-X-X-Gly consensus sequence for the putative FAD-binding domain of microsomal FMO. In marked contrast to the well characterized hepatic and pulmonary forms present in experimental animals, the macacque liver enzyme displayed stereoselectivity for sulfoxidation of p-tolyl methyl sulfide on the pro-S rather than the pro-R face of the substrate. Polyclonal antibodies raised against the macacque liver form exhibited little or no cross-reactivity with major purified forms of the enzyme isolated from rabbit liver, guinea-pig liver or rabbit lung. Anti-macacque liver FMO did not cross react with human fetal liver or adult kidney microsomes, but did recognize a 59 kDa constituent of human adult liver microsomes. The intensity of this immunoreactive 59 kDa band correlated well with human liver microsomal N,N dimethylaniline N-oxygenase activity. We conclude that human adult liver selectively expresses a microsomal FMO which is functionally and immunochemically distinct from the FMO form(s) present in human fetal liver and adult kidney, and from the major hepatic and pulmonary forms present in common laboratory animals. PMID- 8448177 TI - Molecular dynamics simulation of a phospholipase A2-substrate complex. AB - We have used knowledge of the three-dimensional structure of phospholipids and phospholipases A2 together with biochemical data, computer graphics modelling and a 48 ps molecular dynamics simulation to predict the structure of a phospholipase A2-substrate complex. There is remarkable similarity between this predicted structure of enzyme-substrate complex and the structure that can be deduced from the observed enzyme-inhibitor complex. Molecular dynamics simulation highlights the importance of the calcium-ion in substrate binding and the persistence of the His-48 to water-hydrogen bond is compatible with the proposed role of this water molecule as the nucleophile in catalysis. PMID- 8448178 TI - Methylisocyanate and actin polymerization: the in vitro effects of carbamylation. AB - Uremia has been implicated in cataractogenesis due to protein carbamylation by cyanate derived from urea. The present study was designed to directly identify the effects of carbamylation on actin polymerization and the possible contribution to cataract formation. The susceptibility of actin to carbamylation is expected because of the 19 lysines distributed along its length. The lysines of actin were selectively carbamylated by methylisocyanate (MIC) at pH 8.0 and 4 degrees C and actin polymerization assayed by high-shear viscometry, fluorescence and transmission electron microscopy. Our results provide evidence that non enzymatic carbamylation of the lysine residues prevents the polymerization of actin. In addition, this carbamylated actin inhibited the polymerization of nascent, unmodified actin. High-shear viscosity measurements demonstrated decreased initial apparent rates and decreased steady-states (final specific viscosities) of polymerization. Fluorescence measurements showed decreased relative intensities of fluorescence versus control and confirmed the inhibitory effects of carbamylation by MIC on the steady state of F-actin. Transmission electron microscopy (TEM) showed the presence of disorganized filaments when carbamylated actin was added to polymerizing unmodified actin. Our results suggest that carbamylation of actin can cause a loss of ordered filament structure and shape of the lens fiber cell, thus predisposing it to cataract development. PMID- 8448179 TI - Properties of an affinity-column-purified human deoxycytidylate deaminase. AB - Deoxycytidylate deaminase was purified about 7000-fold to homogeneity from a human source (HeLa cells). The final step in the purification employed an affinity column, which increased the specific activity of the enzyme from the previous step by 500-fold. Similar to most other dCMP deaminases, this enzyme is allosterically regulated by microM levels of dCTP and dTTP. However, unlike the other enzymes the most dramatic allosteric responses occur at substrate levels of 0.1 mM dCMP or less, where at least a 10-fold increase in activity is effected by dCTP. The enzyme is particularly sensitive to inhibition by dTTP with 50% inhibition being obtained at 1.5 x (10(-6) M in the absence of dCTP. Antibody to the human enzyme did not cross-react with a dCMP deaminase induced in Escherichia coli by T4-bacteriophage, nor did antibody to the phage-induced enzyme cross react with the human deaminase. A potential transition-state analogue of the substrate, 2'-beta-D-deoxyribose-pyrimidin-2-one 5'-phosphate was prepared, and found to inhibit dCMP deaminase competitively with a Ki of 1.2 x 10(-8) M. PMID- 8448180 TI - Kinetic behaviour of a repressible acid phosphatase from the yeast Yarrowia lipolytica: a comparative study between the solubilized enzyme, the enzyme bound to cell-wall fragments and the enzyme bound to intact cells. AB - (1) The substrate specificities and types of inhibitors of a repressible acid phosphatase from the yeast Yarrowia lipolytica as solubilized enzyme, enzyme bound to cell-wall fragments and enzyme bound to the intact cell were found to be essentially the same. (2) A similar pattern for the activation of the enzymatic activity by ionic strength was found for solubilized enzyme, the enzyme in cell wall fragments and the enzyme in intact cells. (3) v[S] studies with all three locations of the enzyme revealed non-linear Eadie-Hofstee plots with concave-up curves of the negative cooperativity type; these were correctly fitted with a rate equation of 2:2 degree polynomial quotient. In all cases, the same behaviour was obtained and no new kinetic properties were observed when the enzyme was bound to the cell-wall matrix with respect to the solubilized enzyme. (4) Inhibition by phosphate was characterized for the three locations of the enzyme by v[I] and v[S] studies. The same pattern of partial inhibition and non Michaelian inhibition of 'non-competitive' nature was observed for all three forms. (5) The above results are interpreted in terms of the hypothesis that the cell wall of Y. lipolytica has a slight negative charge but behaves as a permeable matrix that does not lead to novel characteristics regarding the catalytic and regulatory properties shown by the enzyme molecule in free solution. PMID- 8448182 TI - Characterization and sequencing of rabbit, pig and mouse angiogenins: discernment of functionally important residues and regions. AB - Rabbit, pig and mouse angiogenins have been purified from blood serum and characterized, and the rabbit and pig proteins have been sequenced fully. A partial sequence of the mouse protein is consistent with the sequence deduced from the genomic DNA (Bond, M.D. and Vallee, B.L. (1990) Biochem. Biophys. Res. Commun. 171, 988-995). All three angiogenins are homologous to the pancreatic RNases and contain the essential catalytic residues His-13, Lys-40 and His-114, and the 6 half-cystines of the human protein. Like human angiogenin they display extremely low ribonucleolytic activities toward wheat-germ RNA, yeast RNA, poly(C) and poly(U). The rabbit and pig proteins induce neovascularization in vivo and also inhibit protein synthesis in vitro. The interaction of rabbit, pig and bovine angiogenins with placental ribonuclease inhibitor, a potent inhibitor of angiogenin, was examined by fluorescence spectroscopy. Rate and equilibrium binding constants indicate that rabbit angiogenin binds to the inhibitor much like human angiogenin, whereas the pig and bovine proteins show significant differences. A comparison of the five angiogenin sequences now available points to specific residues that are highly conserved among them but differ from the corresponding residues in the RNases. These residues are clustered in particular regions of the three-dimensional structure, two of which contribute to the angiogenic, second-messenger and/or protein synthesis inhibition activities of human angiogenin. PMID- 8448181 TI - Novel antibodies specific for proteolyzed forms of protein kinase C: production of anti-peptide antibodies available for in situ analysis of intracellular limited proteolysis. AB - We show here a novel method for the in situ analysis of proteolyzed proteins in a cell. As a model, we focused on protein kinase C (PKC) beta, which is cleaved at a specific site between the catalytic and regulatory domains by calpain, the intracellular calcium-activated neutral proteinase. To detect proteolyzed PKC beta 'cleavage-site-directed antibodies', which specifically recognize the amino terminal region of the catalytic fragment but do not cross-react with the unproteolyzed enzymes, were raised using synthetic peptide. The synthetic peptide used in this study was QGTKVPEEKTT, corresponding to the amino-terminal region of the catalytic fragment from human PKC beta generated by calpain. Rabbits were immunized with the synthetic peptide after conjugation with a carrier protein. Antibodies obtained reacted with the 46-kDa catalytic fragment of PKC beta, whereas they did not cross-react with unproteolyzed enzyme nor other fragments with different amino-termini. Thus, our antibody is specific to the amino terminal sequence QGTKVPEEKTT, but does not recognize the same sequence located internally in native PKC beta. When human monoblast U937 cells were treated with calcium ionophore, the catalytic fragment of PKC beta was detected in the cytosol by immunoblotting with the antibody. However, this antibody did not bind unproteolyzed 80-kDa PKC beta, although this form was dominant in the cytosol of the calcium ionophore-treated cells. We could also detect comparable amounts of catalytic fragment in the calcium ionophore-treated cells by immunocytochemical staining with the same antibody. Our method was applied to examine the proteolysis of PKC beta in neutrophils stimulated with various reagents. PMID- 8448183 TI - FTIR spectroscopy study of PTHrP(1-34) involved in humoral hypercalcaemia of malignancy. AB - The components of secondary structure of the biologically-active N-terminal domain of human parathyroid-hormone-related protein (residues 1-34) and several truncated species were examined using Fourier transform infrared (FTIR) spectroscopy. The major structural features include a segment of alpha-helix within the N-terminal segment probably extending from Glu-4 to Lys-11 with three beta-turns localized to the segments Gly-12 to Ile-15, Gln-16 to Arg-20 and His 25 to Ala-29. Some beta-sheet was detected in the full-length peptide, but not in any of the C-terminal truncated samples. These structural features were studied in the smaller peptides for the purpose of localization of the various components and with a view to describing the region likely to form the bulk of the receptor binding site. PMID- 8448184 TI - Comparative steady-state fluorescence studies of cytosolic rat liver (GTP), Saccharomyces cerevisiae (ATP) and Escherichia coli (ATP) phospho enol pyruvate carboxykinases. AB - Two members of the ATP-dependent class of phospho enol pyruvate (PEP) carboxykinases (Saccharomyces cerevisiae and Escherichia coli PEP carboxykinase), and one member of the GTP-dependent class (the cytosolic rat liver enzyme) have been comparatively analyzed by taking advantage of their intrinsic fluorescence. The S. cerevisiae and the rat liver enzymes show intrinsic fluorescence with a maximum emission characteristic of moderately buried tryptophan residues, while the E. coli carboxykinase shows somewhat more average exposure for these fluorophores. The fluorescence of the three proteins was similarly quenched by the polar compound acrylamide, but differences were observed for the ionic quencher iodide. For the ATP-dependent enzymes, these last experiments indicate more exposure to the aqueous media of the tryptophan population of the E. coli than of the S. cerevisiae enzyme. The effect of nucleotides on the emission intensities and quenching efficiencies revealed substrate-induced conformational changes in the E. coli and cytosolic rat liver PEP carboxykinases. The addition of Mn2+ or of the adenosine nucleotides in the presence of Mg2+ induced an enhancement in the fluorescence of the E. coli enzyme. The addition of guanosine or inosine nucleotides to the rat liver enzyme quenched its fluorescence. From the ligand-induced fluorescence changes, dissociation constants of 40 +/- 6 microM, 10 +/- 0.8 microM, and 15 +/- 1 microM were obtained for Mn2+, MgATP and MgADP binding to the E. coli enzyme, respectively. For the cytosolic rat liver PEP carboxykinase, the respective values for GDP, IDP and ITP binding are 6 +/- 0.5 microM, 6.7 +/- 0.4 microM and 10.1 +/- 1.7 microM. A comparison of the dissociation constants obtained in this work with those reported for other PEP carboxykinases is presented. PMID- 8448185 TI - Hemoglobin Ozieri: a new alpha-chain variant (alpha 71(E20)Ala-->Val). Characterization using FAB- and electrospray-mass spectrometric techniques. AB - A new silent hemoglobin variant, Hb Ozieri (alpha 71(E20)Ala-->Val), was observed in five apparently unrelated newborn babies during a screening for hemoglobinopathies on the island of Sardinia. This asymptomatic variant was detected by means of isoelectric focusing (IEF), isolated using IEF in an immobilized ultranarrow pH-gradient and characterized at the structural level using FAB- and electrospray-mass spectrometric techniques. A Val for Ala substitution was unambiguously detected at position 71 of the alpha-globin chain. This substitution indicates that a C to T transition occurred in the GCG codon for Ala which contains one of the 35 unmethylated CpG dinucleotides of the alpha globin gene. This observation brings the number of variants due to a mutation in the alpha-globin gene CpGs (the third instance of a silent mutation) to 13 and raises the possibility that unmethylated CpGs might be hotspots for mutations as the methylated ones. PMID- 8448186 TI - Structure and function of protamines: an 1H nuclear magnetic resonance investigation of the interaction of clupeines with mononucleotides. AB - Protamines form a class of low-molecular-weight proteins that protect the chromosomal DNA in the spermatic cells of eukaryotic organisms. Protamines are located in the small and/or large groove of DNA where they complex the DNA nucleotides. Very little is known up to date on the role and specificity of binding of the various protamine fractions belonging to a single eukaryotic species. In the present paper, a detailed investigation on the complexation properties of the protamine fractions (clupeines) extracted from herrings has been carried out by means of proton nuclear magnetic resonance and ultraviolet absorbtion data. In particular, the binding properties of the clupeine fractions with purinic (5'dAMP) and pyrimidinic (5'dCMP) mononucleotides have been measured and analysed at different clupeine concentrations. The results indicate that, contrary to previous preliminary hypothesis, the three clupeine fractions exhibit quite comparable binding properties toward mononucleotides. In addition it has been found that nucleotides can induce a conformational transition of the disorder-order type in the clupeine molecules and this property is concentration and temperature dependent. It is concluded that, as far as specificity is concerned, the clupeine fractions seem to possess the same behaviour toward mononucleotides. PMID- 8448187 TI - Determination of the secondary structure of epoxide hydrolase by Raman spectroscopy. AB - The secondary structure of microsomal epoxide hydrolase was determined by Raman spectroscopy and the effect of the membrane microenvironment studied. The ratios of the four secondary structure contents, alpha-helix: beta strand:turn:undefined, were found to be 47:24:17:11 and 58:17:15:10 for the solubilized and the membrane-bound epoxide hydrolase, respectively. Based on the spectral analysis in the 2800-2900 cm-1 range, it was concluded that the protein studied produces the disordering effect on the lipid dimyristoylphosphatidylcholine bilayer at 16 degrees C. PMID- 8448188 TI - Valine dehydrogenase from a non-spore-forming bacterium, Alcaligenes faecalis: purification and characterization. AB - An NAD-dependent valine dehydrogenase (L-valine:NAD oxidoreductase, deaminating, EC 1.4.1.-), was found in a non-spore-forming bacterium, Alcaligenes faecalis, and purified about 80-fold to be characterized. The molecular mass of the enzyme was estimated to be about 72 kDa and the enzyme consists of two identical subunits with a molecular mass of 40 kDa and is thermolabile. It loses its activity fully on incubation at 50 degrees C for 5 min. The enzyme catalyzes the reversible deamination of L-valine, which is the preferred substrate, and other branched-chain and straight-chain L-amino acids in the presence of NAD. The pH optima are about 10.8 and 8.8 for the oxidative deamination and reductive amination, respectively. The pro-S hydrogen at C-4 of the dihydronicotinamide ring of NADH was exclusively transferred to the substrate in the reductive amination. The amino-acid composition markedly differs from those of Bacillus sphaericus and Clostridium thermoaceticum leucine dehydrogenases. The enzyme did not react with the antibody of C. thermoaceticum leucine dehydrogenase. Therefore, the enzyme is clearly different from leucine dehydrogenases from spore forming bacteria, which act on valine, and the first valine dehydrogenase to be characterized in detail. PMID- 8448189 TI - Dimethyl sulfoxide favours the covalent phosphorylation and not the binding of Pi to sarcoplasmic reticulum ATPase. AB - Competition between Ca2+ binding and Pi phosphorylation showed that the affinity of Ca(2+)-ATPase for Pi was not changed by 20% DMSO. Thus, the enhancement of Pi phosphorylation in the presence of DMSO should not be attributed to a solvent effect on the affinity for Pi, but rather on the phosphorylation reaction itself. PMID- 8448190 TI - Identification of autoproteolytic cleavage site in the Asp-49 mutant subtilisin J by site-directed mutagenesis. AB - Ser-49 located at the exposed surface loop of subtilisin J was replaced with Asp and Arg. Proteinase activity of the Asp-49 mutant was similar to that of wild type, but the Arg mutant was inactivated. At 37 degrees C, mature subtilisin J protein of the Asp-49 mutant rapidly degraded, and specific breakdown products were accumulated. These proteins were analyzed by SDS-PAGE, and the N-terminal sequences were determined for the mature and deleted protein. We identified the autoproteolytic cleavage site in the mature Asp-49 mutant protein from sequencing data. PMID- 8448191 TI - Amino-acid sequence of rusticyanin from Thiobacillus ferrooxidans and its comparison with other blue copper proteins. AB - Rusticyanin, a copper protein characterized by a high redox potential (+680 mV) and a high stability at acidic pH, is involved in iron oxidation in Thiobacillus ferrooxidans. It has been characterized from a new strain and its amino-acid sequence has been determined and compared to two other rusticyanin sequences isolated from different strains. It comprises 155 amino acids and the alignment of the three rusticyanins shows a high degree of homology. Comparing the rusticyanins with six blue copper proteins which have a copper-I site in common, a consensus sequence containing Cys, His and Met in the C-terminal part of the protein and His-85 is proposed to be involved in the copper coordination. Secondary structure predictions are compared to three structures of copper proteins obtained by X-ray crystallography. PMID- 8448192 TI - Resistance of archaebacterial aEF-1 alpha.GDP against denaturation by heat and urea. AB - The elongation factor aEF-1 alpha, isolated as aEF-1 alpha.GDP from the thermoacidophilic archaebacterium Sulfolobus solfataricus, exchanges GDP for [3H]GDP at a rate which reaches a maximum at 95 degrees C. The rate constants at different temperatures of the heat inactivation of aEF-1 alpha.GDP are considerably lower compared to those referred to Escherichia coli EF-Tu.GDP. The Tm values determined for both aEF-1 alpha.GDP and EF-Tu.GDP are 97 and 53 degrees C, respectively. The addition of GDP during the heat treatment protects significantly EF-Tu.GDP but only slightly aEF-1 alpha.GDP. The ability of aEF-1 alpha.GDP to exchange GDP for [3H]GDP is impaired at 70 degrees C by urea at concentrations which are greater compared to those required to inactivate E. coli EF-Tu.GDP at 45 degrees C; apparently both factors are not protected by GDP against inactivation by urea. PMID- 8448193 TI - P36, a Dictyostelium discoideum protein whose phosphorylation is stimulated by GDP, is homologous to the alpha-subunit of succinyl-CoA synthetase. AB - Previously, we reported the phosphorylation of a 36 kDa protein, p36, in crude membranes from the amoeba Dictyostelium discoideum (Anschutz, A.L., Howlett, A. and Klein, C. (1989) Proc. Natl. Acad. Sci. USA 86, 3665-3668). Here, we report the purification and identification of p36. The protein was purified approximately 35-40-fold with a yield of 8-10%. This material was then separated on 10% SDS-polyacrylamide gels and the band corresponding to p36 was isolated. Partial peptide sequencing of this band revealed p36 to be homologous to the alpha-subunit of succinyl-CoA synthetase. This identification of the protein was supported by the results of phosphorylation studies which examined the effects of substrates of succinyl-CoA synthetase on p36 phosphorylation. In crude sample preparations, p36 could be phosphorylated by both ATP or GTP and in either case, its phosphorylation was stimulated by low concentrations of GDP. Partially purified p36 retained its ability to be phosphorylated with GTP while exhibiting little or no phosphorylation with ATP. GDP still enhanced the rate of p36 phosphorylation with GTP. Therefore, the stimulation of p36 phosphorylation by GDP is not due to substrate conversion and is best explained by a regulatory mechanism. PMID- 8448195 TI - Two-dimensional crystallization of catalase on a monolayer film of poly(1-benzyl L-histidine) spread at the air/water interface. AB - Two-dimensional (2D) crystals of beef liver catalase were prepared by adsorption to a film of synthetic polypeptide, poly(1-benzyl-L-histidine) (PBLH), spread at the air/water interface. The crystallization experiments were carried out in the pH range of 4.8-6.4 for catalase solutions at low concentration (10 micrograms/ml). The pH-dependence suggested an electrostatic interaction in the binding of catalase to the PBLH film. At lower pH, small crystals were formed at a low binding rate, and at higher pH the binding was rapid and densely-packed 2D arrays with poor crystallinity were formed. To stimulate crystal growth, a thermal treatment was applied. One-shot heating of the interfacial catalase-PBLH film to 35-40 degrees C was remarkably effective to form larger 2D crystals. The structure of catalase 2D crystals has been analyzed by Fourier filtering of the transmission electron micrographs. The crystal form is a new one, containing four catalase molecules in the unit cell with lattice parameters of alpha = 187 A, b = 225 A and gamma = 92.8 degrees. PMID- 8448194 TI - Time-resolved fluorescence of S-100a protein in the absence and presence of calcium and phospholipids. AB - We have used phase-modulation fluorescence lifetime measurements to study the single Trp residue of the Ca(2+)-binding protein S-100a. Trp fluorescence decay was not exponential for the protein irrespective of the absence or presence of Ca2+. Fluorescence decay was best described by Lorentzian lifetime distributions centered around two components (approx. 3 and 0.7 ns) for protein in absence of Ca2+ and one component (approx. 2.9 ns) for the protein in presence of 2 mM Ca2+. Similar studies were performed with S-100a interacting with cardiolipin, phosphatidylserine or egg phosphatidylcholine, both in absence and in presence of 2 mM Ca2+. Our data suggest that the conformation of the protein and its Ca(2+) binding properties vary depending on the characteristics of charge and structure of phospholipids. PMID- 8448196 TI - Studies on the location of aromatic amino acids in alpha-crystallin. AB - The locations of tryptophan residues in alpha-crystallin and homopolymers constructed from the alpha A- and alpha B-chains were examined by comparing their fluorescence emission properties and their accessibilities to quenchers. Two classes of tryptophan could be distinguished on the basis of differences in their spectral characteristics, fluorescence decay lifetimes, quenching with acrylamide and exposure by increasing concentrations of urea. Polarization measurements indicated that the tryptophan residues were associated with flexible segments of the polypeptide chains. The two classes could be assigned, one to Trp-9 (in both A- and B-chains) which is in an hydrophobic environment, and one to Trp-60 (B chain) which appeared to be nearer the surface of the aggregate. No evidence was found for residues inaccessible to the quenchers. An apparent partition coefficient of 40 was obtained for the association of acrylamide with the protein. From temperature-dependence studies, it was concluded that there was a significant energy barrier to the penetration of acrylamide into the protein matrix (Ea = 5.8 kcal/mol) and that entry of the quencher was through channels produced by temporary disruption of the matrix (delta s = 1.5 eu). The phenolic side-chains of tyrosine residues in several different alpha-crystallins were found to ionize with pK values above pH 11, indicative of residues highly shielded from the solvent. Comparisons of polypeptide sequences, together with tyrosine fluorescence emission data and the pK values, permitted a tentative assignment of residue locations. All of the data are consistent with a possible micelle-like structure for alpha-crystallin but not with a layered structure. PMID- 8448197 TI - Specificity for various imino-acid-residues of a proline-specific dipeptidylcarboxypeptidase from a Streptomyces species. AB - A proline-specific dipeptidylcarboxypeptidase, which removes diproline from the C terminus of the proline-containing peptides, such as Boc-Pro-Pro-Pro-Pro and Leu Pro-Pro-Pro-Pro-Pro, has recently been purified from a Streptomyces sp. The specificity of the enzyme for various imino acid-containing synthetic peptide substrates was further studied. The peptides with proline, hydroxyproline, or dehydroproline at the P2' position were found to be good substrates, while those with pipecolic acid, D-proline or other usual amino acids at the P2' position were scarcely hydrolyzed. The peptides with proline, dehydroproline, pipecolic acid, or N-methyl-alanine at the P1' position were well-hydrolyzed, while those with hydroxyproline or D-proline at the P1' position were not hydrolyzed. Utilizing this high specificity for imino acids, Boc-Pro-Pro-Pro-Pro was synthesized by the enzyme using Boc-Pro-Pro as the acidic component and Pro-Pro as the basic component. PMID- 8448198 TI - Oxygen-binding properties of extracellular hemoglobin from the leech, Hirudo medicinalis. Effects of pH, cations and temperature. AB - Electron microscopy of the extracellular hemoglobin from the medicinal leech, Hirudo medicinalis, revealed a typical annelid two-tiered hexagonal structure. The dimensions of the molecule were 30.2 +/- 1.6 nm corner to corner across the hexagon and 18.9 +/- 1.1 nm in height. The oxygenation properties of this high molecular-weight hemoglobin have been thoroughly studied. The effects of hemoglobin concentration, pH, temperature and concentration of specific cations on the oxygen affinity and the degree of cooperativity have been investigated with special consideration given to physiological conditions. At near physiological cation concentrations (6 mM Ca2+, 0.125 M Na+), the oxygen affinity and cooperativity tend to increase with increasing alkalinity. At physiological conditions ((pH 7.5) temperature 20 degrees C), they reach P50 values of 5.0 mmHg and n50 = 3.1. An alkaline Bohr effect with considerable magnitude (phi = -0.50) is observed at pH 7.0-8.0. The oxygen-binding properties are also affected by cations. Both oxygen affinity and cooperativity rise with increasing cation concentrations. Divalent cations, such as Ca2+ and Mg2+, bring about larger effects than monovalent ones. They begin to be effective at concentrations as low as 0.1 mM. The magnitude and position of the Bohr effect of H. medicinalis hemoglobin are controlled by cations to such an extent that this Bohr effect can be predominantly ascribable to the oxygen-linked binding of the physiologically available allosteric effectors Ca2+ and Na+. The results obtained indicate that protons and cations are effective allosteric regulators of achaete (leech) extracellular hemoglobins. PMID- 8448199 TI - Introduction of Ca(2+)-binding amino-acid sequence into the T4 lysozyme. AB - The 51-62 loop of T4 phage lysozyme was altered by site-directed mutagenesis to obtain maximal homology with the typical EF-hand motif. A Ca(2+)-binding site was designed and created by replacing both Gly-51 and Asn-53 with aspartic acid. The mutant T4 lysozyme (G51D/N53D) was expressed in Escherichia coli. The activity of the G51D/N53D-mutant was about 60% of that of the wild-type protein. This mutant can bind Ca2+ ions specifically, while the effective dissociation constant was essentially greater than that of the EF-hand proteins. Stability of the G51D/N53D mutant apo-form to urea- or temperature-induced denaturation was the same as that of the wild-type protein. In the presence of Ca2+ ions in solution the stability of the mutant T4 phage lysozyme was less than that of the wild-type protein. It is suggested that the binding of Ca2+ by the mutant is accompanied by the considerable conformational changes in the 'corrected' loop, which can lead to the Ca(2+)-induced destabilization of the protein. PMID- 8448200 TI - Transition state of an unfolding step in human cyanomet myoglobin. AB - We studied an unfolding step of cyanomet myoglobin (Mb) unfolding, for demonstrating dynamical structural changes in the transition state of the process. Three leucine-->alanine mutant Mbs (L29A, L72A and L104A) were prepared for this study. The urea-induced largely monophasic process was monitored by absorption spectroscopy. Linear relations between [urea] and the activation energy (delta G not equal to) of the relaxation for all the Mbs showed that the slope m not equal to urea (= delta(delta G not equal to)/delta[urea])) was altered by either reduction of pH or the L-->A mutations. Thermodynamic interpretations of the changes in m not equal to urea led to a conclusion that the exposed surface area of Mb in the transition state was determined by both protein-core stability and pH conditions. We also performed urea- and acid denaturation experiments, and gave some inspections on differences between mutational effects on the structure of the transition state and the denatured state. PMID- 8448201 TI - A corrected primary structure for dog-fish Scylliorhinus caniculus protamine Z3. AB - We have redetermined the primary structure for dog-fish protamine using automated amino-acid sequencing associated to mass spectrometry techniques and report, on the basis of these findings, that the previously published amino-acid sequence is incorrect. The correct protamine sequence is 37 amino acids long and differs from the original published sequence by the C-terminal hexapeptide Arg32-Gly-Arg-Arg Ser-Arg37. PMID- 8448202 TI - Theoretical and matrix-isolation experimental studies on 2-thiocytosine and 5 fluoro-2-thiocytosine. AB - 2-Thiocytosine (s2Cyt) and 5-fluoro-2-thiocytosine (f5s2Cyt) were studied by means of IR spectroscopy under different environmental conditions: isolated in low-temperature inert gas matrices, associated in thin amorphous and polycrystalline films. The compounds isolated in matrices were only very slightly influenced by the environment. From the analysis of the IR spectra of both compounds it appears that they exist in inert gas matrices only in the amino thiol tautomeric form. Strong environmental effects were observed for s2Cyt and f5s2Cyt deposited in the form of thin polycrystalline films. Contrary to matrices, in polycrystalline films the amino-thione form dominates for both s2Cyt and f5s2Cyt. The experimental findings are in agreement with the ab initio quantum mechanical calculations of the relative total energies of the tautomeric forms. Those energies were calculated using the Self Consistent Field method corrected for electron correlation effects with the use of the second-order many body perturbation theory (SCF+MBPT(2)). The theoretical calculations show that the amino-thiol tautomeric form is more stable than the amino-thione form by 38 kJ mol-1 and 48 kJ mol-1 for s2Cyt and f5s2Cyt, respectively. Both molecules, s2Cyt and f5s2Cyt, may also appear in the uracil-like imino-thione tautomeric form, which is predicted to be only 8 kJ mol-1 less stable than the amino-thione form. A new method of the preparation of f5s2Cyt is reported. PMID- 8448203 TI - Prodynorphin mRNA expression in adult cultured rat ventricular cardiac myocytes. AB - Prodynorphin mRNA was synthesized both in rat atrial and ventricular tissue, as well as in adult cultured rat ventricular cardiac myocytes. In the cultured cells, the content of prodynorphin mRNA did not differ from that detected in the original ventricle, indicating that the myocardial cell is an important source for prodynorphin mRNA in the rat ventricular tissue. This study demonstrated the presence of immunoreactive dynorphin B-like material in the cultured cardiomyocytes. Gel permeation chromatography analysis of this material revealed the presence of forms with an apparently higher molecular weight than authentic dynorphin B. PMID- 8448204 TI - Effect of a rare leucine codon, TTA, on expression of a foreign gene in Streptomyces lividans. AB - Streptomyces are bacteria with a very high chromosomal G+C composition (> 70 mol%) and extremely biased codon usage. In order to investigate the relationship between codon usage and gene expression in Streptomyces, we used ssi (Streptomyces subtilisin inhibitor) as a reporter gene and monitored its secretory expression in S. lividans. In consequence of alteration of the native codons of Leu, Lys and Ser of ssi to minor ones by site-directed mutagenesis, i.e., Leu79-Leu80: CTG-CTC to TTA-TTA, Lys89: AAG to AAA, Ser108-Ser109: TCG-AGC to TCT-TCT, respectively, the production of SSI was reduced remarkably in the case of TTA codons, while it was slightly increased in the case of AAA and almost the same in TCT codons. This conspicuous decrease found for Leu codon replacement was probably due to the low availability of intracellular tRNA(Leu) (UUA), a product of bldA which has been reported to be expressed only during the late stage of growth. PMID- 8448205 TI - The atp2 operon of the green bacterium Chlorobium limicola. AB - The operon (atp2) encoding the beta and epsilon subunits of F-ATPase from Chlorobium limicola was cloned and sequenced. In contrast with purple bacteria these genes are arranged in a separate operon similar to the cyanobacteria. The operon terminates with a pronounced stem-loop structure. About 0.8 kb upstream of the beta subunit a gene encoding the enzyme phospho enol pyruvate carboxykinase was identified. This gene is transcribed in the opposite direction of the atp2 operon and also ends with a stem-loop structure. These genes of green bacteria are among the first to be sequenced, and therefore the genetic distance between these genes and corresponding genes from other bacteria and eukaryotes was studied. Even though the operon structure resembles that of cyanobacteria, the evolutionary tree compiled from these data places the chlorobium gene close to purple bacteria. Chlorobium limicola beta and epsilon subunits complemented Escherichia coli mutants defective in the corresponding subunits, indicating that the hybrid enzyme formed from subunits of the two bacteria is active in ATP synthesis. PMID- 8448206 TI - cDNA cloning of a hnRNP A1 isoform and its regulation by retinol in monkey tracheobronchial epithelial cells. AB - An isoform of the hnRNP A1 was cloned from a cDNA library of monkey tracheobronchial epithelial (TBE) cells by differential hybridization. The cDNA clone MT77 has an insert of 1756 base pairs and the DNA sequence shares high homology to both human A1 alpha-type and beta-type isoforms with the exception of several differences in the coding and noncoding regions. Like the other two isoforms, MT77 has two polyadenylation sites. A probe prepared from the MT77 clone hybridizes to two message bands at 1.4 and 1.8 kb. Both messages were found in a polysomal preparation, suggesting that both messages are used in A1 protein synthesis. The expression of the A1 gene in monkey TBE cells is stimulated by vitamin A (retinol). The results of nuclear run-on transcriptional assays suggest that this stimulation occurs at the transcriptional level. Furthermore, this effect is not prevented, but superinduced, by cycloheximide. These results suggest that vitamin A may be directly involved in regulating A1 transcription through a mechanism similar to the interactions between the retinoic acid responsive elements and the nuclear receptors of retinoic acid. PMID- 8448207 TI - The dysfunction of coagulation factor VIIPadua results from substitution of arginine-304 by glutamine. AB - This study addresses whether a mutation in the factor VIIPadua gene could explain the reduced activity of the inherited variant protein. All nine exons of the normal and Padua factor VII gene were amplified using the polymerase chain reaction, cloned into pUC19 and sequenced. A point mutation (G to A at nucleotide position 10828) was found which results in the substitution of a glutamine (CAG) for arginine (CGG) at amino acid position 304. This substitution creates a PvuII restriction site useful in screening for the defect and in demonstrating homozygosity. This substitution involves an arginine residue in the catalytic domain within a Leu*****Pro******Cys motif which occurs in conserved region 5 in up to 16 coagulation and other serine proteinases. On the basis of conformational homology among serine proteinases, it is suggested that the observed amino acid substitution in factor VIIPadua could cause structural changes affecting its activation and/or catalytic activity. PMID- 8448208 TI - Molecular cloning and sequence of cDNAs for the import precursors of oligomycin sensitivity conferring protein, ATPase inhibitor protein, and subunit c of H(+) ATP synthase in rat mitochondria. AB - Four cDNAs for the import precursors of oligomycin sensitivity conferring protein (OSCP), ATPase inhibitor protein (IF1) and subunit cs (encoded by P1 and P2 genes) of rat mitochondrial H(+)-ATP synthase have been cloned from a rat cDNA library. The import precursors and the mature polypeptides of rat OSCP, IF1, subunit c (P1) and subunit c (P2) consisted of 23/190, 25/82, 61/75 and 66/75 amino acids, respectively. PMID- 8448209 TI - The insulin-elicited 160 kDa phosphotyrosine protein in mouse adipocytes is an insulin receptor substrate 1: identification by cloning. AB - Insulin elicits the tyrosine phosphorylation of one or more proteins of 160-185 kDa in many cell types. Peptide sequences, obtained from this protein purified from mouse 3T3-L1 adipocytes (pp160), were used as the basis for cloning its cDNA, pp160 is highly homologous to the insulin receptor substrate 1, previously cloned from rat liver. Thus, this component of the insulin signaling pathway is the same in adipocytes and in liver. PMID- 8448210 TI - Primary structure of the nuclear-encoded 10.5 kDa subunit of complex I from Neurospora crassa. AB - We have isolated a cDNA clone for the nuclear encoded 10.5 kDa subunit of complex I from N. crassa. DNA sequencing revealed an open reading frame corresponding to a polypeptide with 94 amino acids and a calculated molecular mass of 10531 Da. The protein is synthesized without a cleavable mitochondrial targeting sequence. The N. crassa polypeptide is the fungal equivalent of subunit B8 of bovine complex I. PMID- 8448211 TI - The nucleotide sequence of a cloned cDNA encoding ribosomal protein S6 from Drosophila melanogaster. AB - A cDNA containing the complete coding sequence for a homolog of eukaryotic ribosomal protein S6 was isolated from a library derived from mRNAs expressed in embryos of Drosophila melanogaster. The cloned cDNA would encode a protein of 248 amino acid residues displaying 74.5% identity with its human homolog. PMID- 8448212 TI - Nucleotide sequences of the Macaca fascicularis apolipoprotein C-III and A-IV genes. AB - The cynomolgus monkey (Macaca fascicularis) apolipoprotein C-III and apolipoprotein A-IV genes have been isolated from a cynomolgus genomic DNA library and completely sequenced. These genes span 3.1 and 2.8 kilobases (kb), respectively. Apolipoprotein C-III gene is interrupted by three intervening sequences of 613, 135 and 1699 bp, respectively. The open reading frame encodes a protein of 99 amino acids which is 87% similar to the human. The cynomolgus mature protein is 79 residues long. Thr-74 is also present what might allow the formation of O-glycosidic linkage observed in the human protein. Apolipoprotein A IV gene consist of two intervening sequences of 352 and 774 bp, respectively. The open reading frame encodes a protein of 429 amino acids which is 87% similar to the human. The cynomolgus mature protein is 409 residues long, 33 amino acids longer than the human, due to an insertion of 33 residues in its COOH-terminal region. This insertion is mainly composed of glutamine and glutamic acid, which confers cynomolgus apolipoprotein a higher hydrophilicity. PMID- 8448213 TI - Molecular cloning and sequence of the cynomolgus monkey apolipoprotein A-II gene. AB - A clone containing the coding region for cynomolgus monkey (Macaca fascicularis) apolipoprotein A-II has been isolated from a cynomolgus genomic DNA library. The gene spans 1.4 kilobases (kb). The complete nucleic acid sequence of the apolipoprotein A-II gene has been determined, establishing that the gene is interrupted by three intervening sequences of 170, 273 and 394 bp, respectively. The open reading frame encodes a protein of 100 amino acids, and shows 94% sequence similarity with its human equivalent. Both apolipoproteins have identical signal peptide. A noticeable feature is the substitution of mature human Cys-6 for Ser. This change explains the existence of cynomolgus apolipoprotein A-II as a monomer and may have important consequences in the kinetics of this apolipoprotein. PMID- 8448214 TI - The barley alpha-thionin promoter is rich in negative regulatory motifs and directs tissue-specific expression of a reporter gene in tobacco. AB - The promoter of the barley alpha-thionin gene (1.6 kb) fused to the beta glucuronidase (GUS) gene directs temporally-controlled, tissue-specific expression in the endosperm of transgenic tobacco. The nucleotide sequence of this promoter shows negative regulatory motifs which have been functionally analyzed in other genes. PMID- 8448215 TI - Identification of the nuclear-encoded chloroplast ribosomal protein L12 of the monocotyledonous plant Secale cereale and sequencing of two different cDNAs with strong codon bias. AB - Two different cDNA clones (SCL12-1 and SCL12-2) encoding precursors of a chloroplast ribosomal protein with homology to L12 from Escherichia coli were isolated from rye leaf cDNA libraries and sequenced. The corresponding polypeptide of rye chloroplast ribosomes was identified. The sequences for the mature proteins of M(r) 13,447 and 13,609 share 85% amino acid identity. The mature polypeptide of clone SCL12-1 has an amino acid identity of 71%, 72% or 44%, respectively, relative to L12 proteins from spinach, tobacco, or E. coli. Codon usage of the rye L12 cDNAs shows a high preference (97% and 82%) for G or C in the third base position. PMID- 8448216 TI - Nucleotide sequence of the Mn-stabilizing protein gene of the thermophilic cyanobacterium Synechococcus elongatus. AB - The nucleotide sequence of the psbO gene encoding the extrinsic 33 kDa protein (the Mn-stabilizing protein) from the thermophilic cyanobacterium Synechococcus elongatus was determined. The deduced amino acid sequence consisted of 272 residues; 26 for the signal peptide and 246 for the mature protein. The amino acid sequences of nine proteolytic peptides from the isolated protein completely agreed with the deduced amino acid sequence. Several unique variations of amino acids were found in the primary structure, of which some may be related to the high thermostability of the protein. PMID- 8448217 TI - The sequence of 5' flanking DNA from the rat preprotachykinin gene; analysis of putative transcription factor binding sites. AB - The rat preprotachykinin A (rPPT-A) gene is expressed in restricted populations of neurons and endocrine cells, including a subset of dorsal root ganglion (DRG) neurons. As part of a study to investigate the DNA sequences responsible for tissue-specific expression of the gene, we have determined the sequence of the 5' flanking DNA to 3350 bp upstream of the transcription start site. The sequenced region encodes a number of putative transcription factor binding sites which may play important roles in the regulation of rPPT-A gene transcription. PMID- 8448218 TI - Ion spray liquid chromatographic/mass spectrometric characterization of bile acids. AB - The ion spray mass spectra of selected bile acid standards are presented. Full scan positive ion spectra obtained in solutions of acetonitrile-water trifluoroacetic acid and methanol-water-trifluoroacetic acid show the presence of intense [M + S + H]+ and [M + 2S + H]+ ions (where S is either methanol or acetonitrile, depending on the solvent system) in addition to [M + H]+ ions. The relative abundance of the protonated and solvent adduct ions are reproducible and unique for several of the bile acids, and provide a means of identifying isomeric bile salts. Adduct ions are most abundant for free acids and weaker for glycine and taurine conjugates. On-line ion spray liquid chromatography/mass spectrometry (LC/MS) using a 3 cm x 4.6 mm cartridge column containing 3 microns particle size C18 packing was utilized for the separation and identification of components of monkey bile. Eight common bile acid conjugates were separated in less than 8 min utilizing a water-acetonitrile gradient with 0.1% trifluoroacetic acid as the mobile-phase modifier. Full-scan data were acquired from 1 microliter of untreated bile injected on-column. Identification of component bile acids from the equivalent of 1 nl injected on-column was obtained with the use of a 1 mm diameter microbore column. Limits of detection for bile acid conjugates using a microbore column and selected ion monitoring (SIM) range from 40 to 100 fmol. PMID- 8448220 TI - Non-enzymatic glycation of histones. AB - 2-(2-Furoyl)-5-(2-furanyl)-1H-imidazole (FFI) is detected in total histones and the lysine-rich histone 1 fraction isolated from calf thymus after in vitro glycation and hydrolysis with HCl, using gas chromatographic/mass spectrometric analysis. The finding suggests that glucose is bound to the epsilon-amino groups of the lysine residues of the histones. No FFI is monitored in native histone samples. PMID- 8448219 TI - Collisionally activated dissociation and tandem mass spectrometry of intact hemoglobin beta-chain variant proteins with electrospray ionization. AB - Electrospray ionization collisionally activated dissociation (CAD) mass spectra of multiply charged human hemoglobin beta-chain variant proteins (146 amino acid residues, 15.9 kDa), generated in the atmospheric pressure/vacuum interface and in the collision quadrupole of a triple-quadrupole mass spectrometer, are shown and compared. Several series of structurally informative singly and multiply charged b- and y-mode product ions are observed, with cleavage of the Thr 50-Pro 51 CO-NH bond to produce the complementary y96 and b50 sequence ions as the most favored fragmentation pathway. The eight different beta-globin variants studied differ by a single amino acid substitution and can be differentiated from the observed m/z shifts of the assigned product ions. The overall fragmentation patterns for the variant polypeptides are very similar, with the exception of the Willamette form, in which Arg is substituted for Pro- 51, and multiply charged y96 product ions are not observed. Circular dichroism spectra of normal beta A and beta Willamette show very little difference under a variety of solvent conditions, indicating that fragmentation differences in their respective CAD mass spectra are substantially governed by primary rather than secondary structure. PMID- 8448221 TI - Investigation of the interaction between enzyme and inhibitor by the combination of chemical modification, electrospray ionization mass spectrometry and frit-fast atom bombardment liquid chromatography/mass spectrometry. AB - The interaction between enzyme and its inhibitor, hen egg-white lysozyme and tri N-acetylglucosamine (NAG3), was studied by the combination of chemical modification, enzymatic digestion, electrospray ionization mass spectrometry and frit-fast atom bombardment liquid chromatography/mass spectrometry. Chemical modification of amino groups, carboxyl groups, and indole groups was carried out independently. In the absence of NAG3, the carboxyl group in Asp 101 was modified by glycinamidation, and the indole group in Trp 62 was modified by Koshland reagent. In the presence of NAG3, the degree of modification of Asp 101 and Trp 62 decreased. It is suggested that Asp 101 and Trp 62 are involved in the interaction with NAG3. The result is consistent with the one obtained by x-ray crystallography. It is indicated that the combination of chemical modification and mass spectrometry may be effective for the investigation of the binding reaction of enzyme to inhibitor and of protein-protein interaction. PMID- 8448222 TI - Quantitative determination of N-acetyl(-L-)cysteine derivatives in human urine by tandem mass spectrometry. AB - Collision-induced dissociation (CID) methods are described for the quantification of nanogram per millilitre (ppb) concentrations of 2-acetamido-3-(3' hydroxypropylthio)-propanoic acid (I) and 2-acetamido-3-phenylthiopropanoic acid (II) in human urine extracts. I and II are potential detoxification products of acrolein and benzene in conjugation with N-acetyl(-L-)cysteine derived from glutathione. We have studied the potential of tandem mass spectrometry (MS/MS) under electron impact (EI) and chemical ionization (CI) conditions as a confirmatory screening technique for these compounds. Our main goals were high selectivity and low detection limits along with little or no sample clean-up. The effects of the mode of ionization and of collision conditions on the CID spectra have been investigated. Direct insertion probe without any derivatization or short-column gas chromatographic separation techniques are used. Total instrument and data analysis time is about 15 min for direct insertion probe MS/MS and about 30 min for short-column gas chromatography (GC)/MS/MS. Detection limits are: direct insertion probe MS/MS (EI mode), 50 ppb (100 pg) for compound I; short column GC/MS/MS (EI mode), 1.5 ppb (5 pg) for compound II; and short-column GC/MS/MS (CI mode), 0.6 ppb (2 pg) for the methyl ester of compound II. Results are compared with non-mass spectrometric methods. The MS/MS methods were applied for the determination of I (EI mode) and II (CI mode) in urinary samples of a smoker and eight non-smokers. After smoking, the urinary levels of I and II were elevated, whereas no increase was observed after experimental passive smoking. PMID- 8448223 TI - [Benefits of x-ray diagnosis]. PMID- 8448224 TI - [New imaging methods in thoracic diagnosis. A study to evaluate digital storage screen radiography, the slit technique ("AMBER"), asymmetric ("InSight") and conventional film-screen techniques]. AB - New methods have been introduced in recent years in chest imaging to achieve high image quality simultaneously in the mediastinum and in the lung field. In this study the clinical value is assessed for four techniques: digital storage phosphor radiography, slit-technique ("AMBER"), asymmetrical film/screen ("InSight") and conventional film/screen. 43 patients were examined with these techniques within one day. Seven readers of four universities graded the image quality according to ten criteria of the mediastinum and the lung field. The slit technique ("AMBER") showed the best image quality in both areas. Compared to conventional film/screen, storage phosphor radiography and asymmetrical film/screen ("InSight") yield better image quality only in the mediastinum. PMID- 8448225 TI - [Radiation exposure in computed tomography]. AB - The axial dose profile of various scans of different CTs was determined to obtain specification on radiation geometry by collimation. The dose was measured "free in-air" by thermoluminescent dosimeters at the axis of rotation. Considerable differences between the various CTs were observed. The scans of different CTs had narrow and wide fields. It seems to be possible to reduce the energy transmitted to the body by appropriate collimation. PMID- 8448226 TI - [Radiation protection measures for diagnostic x-ray equipment]. AB - The operation of x-ray equipment requires protective devices, organisational measures and observation of rules. First of all, the paper deals with typical dose values of scattered radiation and the consequences for the absorbed dose. Classification into areas subject to routine supervision and to close control, and into protected areas, is explained. The major part of the paper deals with the radiation protection measures of typical diagnostic x-ray equipment. PMID- 8448227 TI - [A comparison of two noninvasive measurement methods for determining central osteoporosis taking into consideration the ash content]. AB - Two noninvasive methods for measuring bone mineral density are compared (DE-QCT; DEXA). Accuracy was determined by ash weight and real bone density. 40 human cadaver spines (D5, D11, L3, L5) were examined. There was significant high correlation between DE-QCT and real bone density (r = 0.9, alpha < or = 0.001) and only small correlation with -DEKA (r = 0.5, alpha > or = 0.05) in the cases with osteoporotic and none osteoporotic vertebra. DE-QCT seems to be a valuable method for measuring central bone mineral density. PMID- 8448228 TI - [Diagnosis of thrombophlebitis of the leg using duplex sonography]. AB - In a prospective study 113 extremities of 98 patients with suspected lower extremity deep venous thrombosis were examined by duplex sonography and phlebography. In 66 examinations phlebography demonstrated fresh thromboses which were limited to the calf in 14 cases. In all other cases thrombosis was partially or totally localized above the knee. Duplex sonography had a sensitivity in detection of thromboses of 91% (calf veins) up to 94% (proximal veins) and a specificity of 95% and 97%, respectively. Duplex sonography is a reliable method in diagnosis of thrombosis in the popliteal, superficial and common femoral und distal iliac vein. If phlebography is contraindicated, duplex sonography is the method of choice. It should also be performed additionally to phlebography to visualise surrounding tissue and detect the possible cause of thrombosis and clinical symptoms. Duplex sonography can also visualise veins that are not shown phlebographically. PMID- 8448229 TI - [Computed tomography of the digestive tract]. AB - Computed tomography (CT) of the gastrointestinal tract is mostly employed in the staging of malignant lesions. Additionally, the application of CT in the diagnostic work-up of unclear abdominal complaints becomes more and more widespread. These different indications require adequate and standardised examination procedures. In this publication the general principles of gastrointestinal CT are presented, and the characteristic CT features of malignant and benign diseases are illustrated. The advantages, limitations and common pitfalls are pointed out. PMID- 8448230 TI - [MR-myelography of the lumbar spine using a PSIF sequence: first experiences]. AB - A rapid gradient-echo acquisition (PSIF) was used to delineate the lumber spine. Because this sequence is heavily T2 weighted the cerebrospinal fluid shows a bright signal, the myelon has a poor signal. 5 healthy volunteers and 5 patients with suspected lumbar disc herniation were examined by this technique. All MR myelograms were compared with spin-echo sequences (sagittal and transversal slices). All lumbar disc herniations which were recognized by MRI were also delineated by MR myelography. PMID- 8448231 TI - [Cholelithiasis in childhood]. AB - Ultrasound examination of the abdomen permits us to diagnose in childhood much more bile duct calculi than before. Surgery is not necessary in all cases but a follow-up with ultrasound is usefull. PMID- 8448232 TI - [New analog and digital imaging techniques for chest diagnosis--principles- clinical value--economics]. AB - For chest imaging new analog and digital imaging techniques are now available. In this publication the imaging methods conventional film/screen, asymmetric film/screen("In-Sight"), slit(AMBER)-technique, spotfilm(100 mm)-technique, storage phosphor radiography and digital image intensifier radiography are compared. The clinical value is discussed by measured imaging capabilities and patient examinations. The highest image quality was demonstrated by the slit(AMBER)-technique. In comparison to conventional film/screen, storage phosphor radiography and asymmetric film/screen was graded higher only in the mediastinal field. Because of the low spatial resolution the image quality of digital image intensifier radiography was classified too poor for chest imaging. PMID- 8448233 TI - [Granulomatous mesenteritis in CT]. AB - The authors report on the clinical pattern of symptoms and on conventional and CT diagnostics of a granulomatous mesenteritis. The differential diagnoses are discussed. PMID- 8448234 TI - [Tuberculosis of the pancreatic region--sonographic and CT findings]. AB - In the case reports of two black men of 29 and 32 years of age the rare condition of tuberculous involvement of the pancreas is described. The diagnosis was established by exploratory laparotomy and by the culture of mycobacterium tuberculosis. Ultrasonography demonstrated inhomogeneous, hypoechoic masses in and around the pancreas. Contrast-enhanced computed tomography of the abdomen revealed enlargement of the pancreas and the presence of lesions of decreased attenuation or cystic collections with involvement of the peripancreatic area. PMID- 8448235 TI - [Quality assurance in x-ray diagnosis]. PMID- 8448236 TI - Immunological responses of breast cancer patients to behavioral interventions. AB - This article reports the results of an 18-month study of immune system and psychological changes in stage 1 breast cancer patients provided with relaxation, guided imagery, and biofeedback training. Thirteen lymph node negative patients who had recovered from a modified radical mastectomy were randomly assigned to either an immediate treatment or a delayed treatment control group. Multiple pre post psychological measures were performed. Significant effects were found in natural killer cell (NK) activity (p < .017), mixed lymphocyte responsiveness (MLR) (p < .001), concanavalin A (Con-A) responsiveness (p < .001), and the number of peripheral blood lymphocytes (PBL) (p < .01). No significant psychological changes were detected; however, reductions were seen in psychological inventory scales measuring anxiety. The results show that behavioral interventions can be correlated with immune system measures, thereby replicating the results of an earlier pilot study from our Center. Discussion is provided on differential T-cell and B-cell responsiveness to behavioral interventions. PMID- 8448237 TI - Self-regulation of slow cortical potentials in psychiatric patients: alcohol dependency. AB - Ten unmediated alcohol-dependent male inpatients participated in a Slow Cortical Potential (SCP) self-regulation task utilizing biofeedback and instrumental conditioning. These patients were hospitalized for treatment of alcohol dependency after chronic abuse of alcoholic beverages. Somatic withdrawal symptomatology had occurred recently and the patients were free of any withdrawal symptoms of the autonomic nervous system. Immediately after hospitalization patients were unable to control their SCPs without the reinforcement of immediate feedback across 4 sessions. Seven patients participated in a fifth session an average of 4 months later. Six out of these 7 patients had not had a relapse at the follow-up. In the fifth session these patients were immediately able to differentiate between the required negativity and negativity suppression, whereas the seventh patient, who had relapsed, was unable to control his brain potentials successfully. Results are further evidence that some of the frontocortical dysfunctions in alcohol-dependent patients are reversible. This could covary with a morphological restitution of the cortex. PMID- 8448238 TI - Ten-year stability of EEG biofeedback results for a hyperactive boy who failed fourth grade perceptually impaired class. AB - Ten years ago, the first successful application of a clinical, private-practice based, EEG 14-Hz biofeedback training regimen for the treatment of learning disorders was performed by the author. After the 10-year-old boy, with presenting symptomatology including a developmental reading disorder, hyperactivity, and an educational classification of perceptually impaired, continued symptom free for a period of two years, his case was submitted for publication. Ten years after his termination from successful treatment, his ongoingly normal social and academic functioning is noted and his EEG brainwave signature examined and compared with a population of 24 "used-to-be" learning disabled, one-half of which had a pretreatment state including the educational classification of perceptually impaired. This 10-year follow-up confirms the long-term stability of the results of this EEG 14-Hz biofeedback regimen. Current findings on recent medical research identifying a major cerebral locus of dysfunction for hyperkinesis and how it supports the electrode placements of this clinical office setting regimen is also discussed. PMID- 8448239 TI - The use of ambulatory EMG monitoring to measure compliance with lumbar strengthening exercise. AB - This study validates the use of ambulatory EMG monitoring as a measure of exercise compliance. The model rehabilitative exercise used was the Prone Back Extension. Thirty-two undergraduate volunteers were videorecorded as they performed the exercise alone in a closed room. The correlation between a direct observation count of the number of repetitions and an independent EMG-based count was .95. EMG amplitude was examined by repetition and gender with regression and ANOVA. There were significant gender differences in the amplitude of EMG across repetitions. There were no significant differences by gender in the declining slope of amplitude across repetitions. This slope may represent a typical "fatigue" curve. Thus, not only the occurrence but also the intensity of exercise can be quantified. PMID- 8448240 TI - What is theta? PMID- 8448241 TI - All-trans retinoic acid plus low doses of cytarabine for the treatment of "poor risk" acute myeloid leukemias. AB - Thirteen refractory/resistant AML patients no suitable for additional aggressive chemotherapy, were treated with a combination including all-trans retinoic acid (45 mg/m2 sine die) and low doses of Ara-C (20 mg/m2 subcutaneously, twice in a day, days 1-10, every 28 days). Ten patients were evaluable; 8 of them achieved a complete remission, two patients with an important tumor burden, failed to achieve a response. One complete remission patient relapsed after 7 months but is still receiving the same therapy and is now in partial remission. We believe this combination effective as inducer of complete remission in those AML patients which cannot tolerate additional heavy treatments. The role of tumor burden in affecting response to therapy remains to be still evaluated. PMID- 8448242 TI - Cytokine serum levels during treatment with high-dose recombinant human IL-3 in a patient with severe aplastic anemia. AB - A 37-year-old woman with severe aplastic anemia (SAA), who had relapsed 6 years after antilymphocyte globulin therapy, was treated with intravenous recombinant human IL-3 (4 micrograms/kg/d) for 21 days. Subsequently, long-term therapy with subcutaneous rhIL-3 at the highest dose level tested so far (16 micrograms/kg/d) was initiated in order to maintain growth-factor response. Therapy was discontinued on day 73 due to progressive thrombocytopenia and increased petechial bleeding. Both treatment schedules resulted in a transient increase in leukocytes (twofold) due to an increase in monocytes, neutrophils, and eosinophils. RhIL-3 had no effect on hemoglobin values or platelet counts and only marginally improved colony formation of bone marrow CFU-GM in response to rhGM-CSF. Side effects of both treatment schedules were mild and did not exceed WHO grade II. Steady-state serum concentrations of IL-3, which are able to stimulate hematopoiesis in vitro (i.e. > 1 ng/ml), were achieved by both low- and high-dose treatment, although high-dose treatment resulted in markedly higher serum levels of IL-3. On measuring cytokine serum levels (neopterin, IL-1 beta, IL-6, sIL-2R, GM-CSF, TNF-alpha, IFN-gamma) we noticed a different cytokine pattern with both treatment modalities, resulting in a moderate induction of TNF alpha and IFN-gamma during low-dose, intravenous treatment, whereas during subcutaneous, high-dose treatment a profound increase of IL-6, sIL-2R, and, to a lesser extent, neopterin was detected. These results in a single patient with SAA indicate that further studies on IL-3 serum levels and IL-3-induced secondary cytokines in a larger group of patients are needed to optimize growth-factor treatment and to better understand the in vivo biological activity of IL-3. PMID- 8448243 TI - On the reliability of clinical criteria for the diagnosis of hepatic veno occlusive disease. AB - Among 217 patients who received an allogeneic (136 cases) or autologous (81 cases) bone marrow transplant, the diagnosis of hepatic veno-occlusive disease (VOD) was established in 38 according to Seattle clinical criteria. Thirty-two underwent a transjugular liver biopsy and measurement of the hepatic venous pressure gradient (HVPG). The study was completed in 30 patients with no serious complications. Hepatic VOD was histologically confirmed in 18 patients (60%); the remaining 12 were classified as non-VOD. An increased HVPG discriminated well between VOD and non-VOD cases. Thus, hemodynamic data can considerably reinforce the accuracy of histological diagnosis. The predictive value of two vs. three clinical data of the Seattle criteria was analyzed. Among the 19 cases fulfilling two clinical data VOD was confirmed in only eight (42%), whereas VOD was proved in ten of 11 cases (91%) (p = 0.02) suspected on the basis of three clinical data. When reliability of the Baltimore clinical criteria was analyzed, the result was identical to that observed when three Seattle clinical data were present. The specificity of the latter classification was high (92%) while its sensitivity was relatively low (56%). In conclusion, clinical criteria are not reliable for either recognizing or excluding the diagnosis of VOD. Thus, a transjugular liver biopsy, associated with hemodynamic evaluation, is strongly recommended when VOD is clinically suspected. PMID- 8448244 TI - Prognostic relevance of histological findings on bone marrow biopsy in myelodysplastic syndromes. AB - Bone marrow biopsy (BMB) has aroused growing interest as a possible aid in the diagnostic and prognostic evaluation of myelodysplastic syndromes (MDS). Previous reports have pointed out that MDS patients with blastic aggregates or severe bone marrow (BM) fibrosis are characterized by a worse clinical outcome. BMBs of 106 MDS patients were retrospectively reviewed, and relationships among the different histological parameters as well as clinicopathological correlations were looked for. Three patterns of BM blastic infiltration ("diffuse," "cluster," and "large") were recognized. Overt leukemic transformation and overall survival were selected as prognostic end points. BM infiltration was "diffuse" in 18, "cluster" in 48, and "large" in 40 cases. RAEB-t patients accounted for about half of the "large" cases, and none had a "diffuse" pattern (p < 0.01). Nineteen patients showed extensive BM fibrosis; most of them were characterized by "cluster" blastic infiltration and megakaryocyte hyperplasia. Leukemic transformation occurred in 67% of "large" cases (p< 0.001) and in none of the "cluster" cases with severe BM fibrosis (p < 0.01); however, survival was equally poor in these two groups because of early leukemic transformation (large cases) and BM failure (cluster cases). The FAB classification did not significantly correlate with prognosis. Patients with "cluster" BM infiltration and severe fibrosis can be regarded as a true separate MDS subset characterized by unique clinicopathological and prognostic features. Because of the subacute clinical behavior of most cases, and the poor performance status of many elderly patients, there is still controversy as to the best therapeutic approach in MDS. Histological analysis allowed two groups of MDS patients to be identified, both characterized by poor life expectancy, who could benefit from early aggressive chemotherapy. PMID- 8448245 TI - Monoclonal gammopathy of unknown significance in a bone marrow donor. AB - We report on a patient suffering from multiple myeloma, for whom allogeneic bone marrow transplantation was planned. Donor workup revealed monoclonal gammopathy of unknown significance. We discuss this finding and stress the importance of performing complete donor examinations. PMID- 8448246 TI - Fluorescence microscopy of fresh tissue as a rapid technique for assessing early injury to mesophyll. AB - A technique was developed for sectioning fresh red spruce foliage (Picea rubens Sarg.) for use in fluorescence microscopy. This allowed rapid examination of mesophyll in 3-5 mm needle sections. Healthy, ozone treated and cold stressed needles were examined to assess the utility of this technique for early detection of damage. Healthy mesophyll cells fluoresced bright red, while injured cells fluoresced yellow-green in ozone treated needles, and yellow-orange green in ozone treated needles, and yellow-orange in frozen needles. Shifts in fluorescence wave-lengths may be useful for early detection of injury to mesophyll before it is evident by standard light or electron microscopy. PMID- 8448247 TI - Keeping plant tissue slices attached to the slide during harsh extraction of polysaccharide. AB - During extraction of hemicellulose and noncellulose polysaccharides from plant histological slices of plants the morphological integrity of the slices may be disturbed if the reagents extracting hemicellulose and noncellulose polysaccharides are rinsed away by water. Removing the reagents by delicate suction rather than removing the glass tray from the staining dish, followed by desiccation and a rinse in 95% ethanol terminates the treatment without altering the morphology of the tissues. PMID- 8448248 TI - A new antiroll device for cryostat wax sectioning. AB - A new antiroll device has been developed to replace the antiroll guide plate for cryostat wax sectioning. With this device, a continuous ribbon of 3-4 microns sections can be obtained. The sections are flat, uncreased, and compression is reduced to a minimum. PMID- 8448249 TI - Technique for in situ excision of distended samples of greater omentum from small laboratory animals. AB - A simple and reliable technique is described for in situ excision of distended samples of greater omentum from small laboratory animals. The omental bursa is distended by injecting whipped hen egg white. Filter paper frames then are applied to the selected areas of distended omentum and samples of omental membrane are excised together with the filter paper frames. This sampling technique yields undamaged materials suitable for various research purposes. PMID- 8448250 TI - Producing frozen sections of calcified bone. AB - We describe a procedure for the rapid production and maintenance of fresh frozen bone biopsies which can be used for a variety of immunohistochemical techniques. Within 5 min of excision, tissue is placed in cold 5% polyvinyl alcohol, surrounded with 3% carboxymethylcellulose in a hand made aluminum foil embedding mold and frozen by immersion in an absolute ethanol/dry ice slurry at -70 C. The tissue block is attached to the specimen stub with cryocompound and installed in a -32 C cryostat whose tungsten carbide D profile knife is maintained at -70 C. Automatic controls are set at a slow cutting speed and the "sectioning window" is adjusted to fit the biopsy size. Knife angle, thickness gauge and antiroll bar are changed to produce a complete section. The block face is smoothly "papered" with a polyvinylpyrrolidone (PVP) impregnated Ross lens paper strip. A single section is cut and positioned on a sequentially numbered, acid cleaned, double dipped chrome-alum gelatin coated slide; adhesion is aided by "press-blotting" with bibulous paper. Sections are stored at -20 C or in a desiccator at room temperature. A brief fixation followed by removal of the water soluble PVP and lens paper generates fresh frozen bone sections suitable for further analysis. PMID- 8448251 TI - Comparisons of endothelial cell G- and F-actin distribution in situ and in vitro. AB - Numerous studies have described the F-actin cytoskeleton; however, little information relevant to G-actin is available. The actin pools of bovine aortic endothelial cells were examined using in situ and in vitro conditions and fluorescent probes for G-(deoxyribonuclease I, 0.3 microM) or F-actin (phalloidin, 0.2 microM). Cells in situ displayed a diffuse G-actin distribution, while F-actin was concentrated in the cell periphery and in fine stress fibers that traversed some cells. Cells of subconfluent or just confluent cultures demonstrated intense fluorescence, with many F-actin stress fibers. Postconfluent cultures resembled the condition in situ; peripheral F-actin was prominent, traversing actin stress fibers were greatly reduced and fluorescent intensity was diminished. Postconfluency had little influence on G-actin, with only an enhancement in the intensity of G-actin punctate fluorescence. When post confluent cultures were incubated with cytochalasin D (15 min; 10(-4) M), F-actin networks were disrupted and actin punctate and diffuse fluorescence increased. G actin fluorescence was not altered by the incubation. Although its unstructured nature may account for the minor changes observed, the stability of the G-actin pool in the presence of notable F-actin modulations suggested that filamentous actin was the key constituent involved in these actin cytoskeletal alterations. A separate finding illustrated that the concomitant use of actin probes with image enhancement and fluorescent microscopy could reveal simultaneously the G- and F actin pools within the same cell. PMID- 8448252 TI - Metabolism of phospholipids in rat kidney during development. AB - We have examined the phospholipid content and metabolism in renal papilla, medulla and cortex in 10- to 70-day-old rats. No changes in papillary and medullary phospholipids with an increase in cortical phosphatidylcholine and phosphatidylethanolamine were evident during maturation. Phosphatidylinositol de novo synthesis did not change with age, but a decrease in medullary and cortical phosphatidylcholine and phosphatidylethanolamine was observed. In the three zones [14C]arachidonic acid incorporation into all the phospholipids was the highest at 10 days with a gradual decrease with age, while the [14C]palmitic acid incorporation remained unchanged except for phosphatidylinositol which decreased from 10 to 70 days. PMID- 8448253 TI - Glycogen phosphorylase: developmental expression in rat liver. AB - The developing fetus is vulnerable to hypoglycemia if its transplacental substrate supply is compromised. Consequently, we examined hepatic glycogen phosphorylase gene expression in the developing rat liver by comparing the relative activities of the hepatic phosphorylase enzyme, concentrations of cellular phosphorylase mRNA, and rates of transcription in isolated liver nuclei of fetal rats at 19 days of gestation, 21 days of gestation, neonatal rats, and suckling rats. Cellular phosphorylase mRNA and enzyme activity (total and phosphorylase a) increased until term. Reciprocally, the rate of phosphorylase mRNA transcription was rapid in the rats at 19 days of gestation, and declined progressively until term. These data indicate that glycogen phosphorylase gene expression is regulated post-transcriptionally in late gestation, perhaps by an increase in phosphorylase mRNA stability towards term. This results in increased phosphorylase mRNA and enzyme expression. PMID- 8448254 TI - Cerebral blood flow measurements in the newborn dog. AB - Current methods of cerebral blood flow (CBF) determination provide only discrete, episodic data and are limited in assessing dynamic changes in cerebral circulation. We adapted a venous outflow technique employing cannulation of the superior sagittal sinus in newborn puppies to measure changes in CBF rapidly and sequentially during ventilatory maneuvers. CBF velocity (CBFV) was measured simultaneously with Doppler ultrasound of the anterior cerebral artery. Relationships between flow and velocity were determined during hypocarbia, hypercarbia, hypoxia and asphyxia. During hyperventilation, CBF decreased by a mean of 14%, and CBFV by 13%, whereas maximal CO2 inhalation increased CBF by 59% and CBFV by 110%. Although CBFV exhibited the same directional changes as shown by the area under the velocity curve, the magnitude of change was not proportional to flow. CBFV indicated trends in the direction of changes in flow in individual animals, but did not correlate with flow between animals. A fluctuating unstable pattern of CBFV, previously associated with neonatal intracranial hemorrhage, was demonstrated with hyperventilation and hypocarbia. During asphyxia, CBFV ceased 2-5 min prior to CBF, presumably reflecting continued brain perfusion from vessels other than anterior cerebral artery. PMID- 8448255 TI - Fetal pH improvement after 24 h of severe, nonlethal hypoxia. AB - The accumulation of hydrogen ions in fetal blood when fetal oxygenation is acutely decreased suggests metabolic instability. However, in 6 chronically prepared fetal sheep whose arterial O2 content and pO2 were abruptly reduced and maintained at about 1.7 mM and 12.6 Torr, respectively, we observed a significant decrease in fetal arterial lactate concentrations and an increase in pH to normal values after 24 h of continuous hypoxia compared with values observed after 5 h. This demonstrates that fetal pH measurements may not detect prolonged intrauterine hypoxia. PMID- 8448256 TI - Elevated venous concentrations of vasoactive intestinal polypeptide in cord blood of infants with fetal distress. AB - Concentrations of vasoactive intestinal polypeptide (VIP) in cord plasma were determined in 70 neonates (birth weight, mean +/- SD, 3,213.5 +/- 50.9 g, gestation 39.5 +/- 0.2 weeks), 22 of whom had fetal distress. Arterial VIP levels in cord blood were not significantly different between infants with and without fetal distress. The mean venous VIP in cord blood of distressed infants (28.1 +/- 8.4 pg/ml, mean +/- SE) was significantly (p < 0.05) higher than that of normal neonates (12.6 +/- 3.4 pg/ml). The mean placental content of VIP was 5.1 +/- 0.3 ng/g wet tissue, although a correlation with the venous concentration in the cord was not demonstrated. Venous VIP levels were elevated 24 h after birth (34.6 +/- 13.7 pg/ml) and decreased on the 5th day of life to 12.9 +/- 3.8 pg/ml, which was not significantly different from the mean VIP level in childhood (14.7 +/- 3.1 pg/ml). These results demonstrate that, in the perinatal period, plasma VIP levels are elevated on two occasions: at delivery associated with fetal distress (cord vein), and at 24 h of age. VIP in the former seems to be of placental and/or maternal origin. PMID- 8448257 TI - Use of preestablished criteria for deciding on extubation in the very low birthweight newborn. Preliminary analysis of a randomized study. AB - The duration of mechanical ventilation (MV) in very low birthweight infants can sometimes be very prolonged, even in the absence of any respiratory disease. To avoid this, we have developed a double-blind study protocol of the concomitant use of caffeine and doxapram or caffeine and placebo as an aid to early weaning from MV. This protocol necessitated the definition of very precise ventilatory criteria for extubation. Even before the double-blind code has been broken, we can note that the duration of ventilation was very significantly reduced (p < 0.001) from 27.5 days (median; range 1-99) in infants of the retrospective study group to 4 days (median: range 1-34) in the prospective study group (extubation according to strict criteria). This reduction in duration of MV cannot be explained by a difference in the severity of the initial pathology, or by the treatment of some of the infants with doxapram (the difference would not be so marked), but, probably, to the definition of strict criteria concerning extubation. PMID- 8448258 TI - Flavin adenine dinucleotide levels in erythrocytes of very low birthweight infants under vitamin supplementation. AB - Despite the potential dangers of over- and undersupplementation with riboflavin (vitamin B2), little is known about status, requirements and metabolism of this vitamin in very low birthweight (VLBW) infants. As reported here, it is possible to calculate the intraerythrocytic concentration of free flavin adenine dinucleotide (FAD), the predominant coenzyme form of riboflavin, on the basis of the erythrocyte glutathione reductase activation coefficient (EGRAC). This parameter was determined in 9 VLBW infants (median of birthweight 634 g, median of gestational age 24 weeks + 3 days) at intervals over a period of 6 weeks. All infants received riboflavin supplementation, either in milk (average intake: 175 micrograms/kg/day) and a multivitamin preparation (200 micrograms/day) or via total parenteral nutrition (TPN; 720 micrograms/kg/day). The average EGRAC was 1.07 (1.00-1.24) during enteral nutrition and 1.05 (1.00-1.18) during TPN. These values correspond to free FAD levels of 757 and 1,060 nM, which is 4 to 5 times higher than in cord blood or in breast-fed infants. EGRAC values between 1.15 and 1.35, representing free intracellular FAD levels of 350-150 nM, should be adequate in VLBW infants in order to minimize the hazards of flavin-induced radical reactions. PMID- 8448259 TI - Comparative disposition kinetics of 111In-labeled group B streptococcus and neutrophils during onset of sepsis-induced pulmonary hypertension. AB - Little is known of the time course by which intravascular group B streptococcus (GBS) distributes into the infant lung, though the prompt onset of pulmonary hypertension in GBS-infected animals suggests that bacteria interact initially with a resident lung cell or that they promote rapid pulmonary influx of circulating effector cells. Using external gamma scintigraphy to monitor the organ-specific disposition kinetics of 111In-oxine-labeled GBS in anesthetized piglets, we found that 80% of the infused bacteria rapidly distributed into the lung and that pulmonary bacterial uptake exhibited a close temporal relationship with the onset of pulmonary hypertension. Companion studies demonstrated that the extent of pulmonary 111In-neutrophil sequestration was unaffected by GBS, although a neutrophil secretagogue, phorbol myristate acetate, caused rapid pulmonary neutrophil uptake. These observations support the hypothesis that the onset of pulmonary hypertension in GBS sepsis can be attributed to interactions between the bacteria and resident lung cells. PMID- 8448260 TI - Surfactant improves lung function and morphology in newborn rabbits with meconium aspiration. AB - Nearly mature newborn rabbits (gestational age 29.5 days) were tracheotomized at birth and received, via the tracheal cannula, 6 ml/kg body weight of a filtered saline suspension of human meconium, 65 or 130 mg/ml. Animals were kept in body plethysmographs and ventilated for 60 min with standardized tidal volume (8-10 ml/kg). Aspiration of meconium caused, in both groups, a statistically significant reduction in lung-thorax compliance, elevated PCO2 in heart blood and reduced alveolar volume density (VV) in histological sections. Both groups responded to treatment with exogenous surfactant (Curosurf, 200 mg/kg) with a moderate, statistically significant improvement in lung-thorax compliance, PCO2 and alveolar VV. Our data indicate that respiratory failure after neonatal meconium aspiration may be influenced favorably by treatment with exogenous surfactant. PMID- 8448261 TI - Once bitten, twice shy: beyond the conditioning model of PTSD. PMID- 8448262 TI - Brain lithium concentrations measured with lithium-7 magnetic resonance spectroscopy in patients with affective disorders: relationship to erythrocyte and serum concentrations. AB - Brain lithium concentrations were measured in eight patients with affective disorders using lithium-7 magnetic resonance spectroscopy (MRS). Brain lithium concentrations correlated better with serum concentrations (n = 23, r = 0.66, p < 0.001) than with erythrocyte concentrations (r = 0.44, p < 0.05). Because of previous data in animal experiments these results were unexpected, but the differences in cation transport mechanisms between neurons and erythrocytes may account for the results. PMID- 8448263 TI - Two-Hz wide EEG bands in Alzheimer's disease. AB - Twenty Alzheimer's Disease (AD) patients in a mild to moderate stage of the disease and 20 control subjects were compared in 17 2-Hz wide bands from the electrodes 01, 02, P3, P4, T5, T6, F3, F4, F7, F8, Fp1, and Fp2. Differences reached statistical significance for 0-2 and 4-6 Hz bands, where AD patients presented highest power values. The AD group was divided into two groups according to the stage of disease. Both groups of patients presented 0-2 Hz increase in frontal, right parieto-temporal, and occipital areas. The increase in 4-6 Hz band was mainly over frontal areas in both groups and over left parietal region in moderate AD patients. These results and those relative to dominant frequency and crossover frequency between groups are discussed according to previous results with conventional and 2-Hz wide bands in AD patients in a severe stage of the disease. PMID- 8448264 TI - A double-blind placebo-controlled glucose challenge in bulimia nervosa: psychological effects. AB - Nineteen bulimic women and 22 age-matched controls were randomly assigned to receive 25 g of glucose or a placebo injection under double-blind conditions. Blood samples of glucose, insulin, and glucagon, and psychometric assessments of mood and food cravings were obtained 10 min before, and 0, 5, 10, 20, 30, 45, and 60 min after injection. Blood levels of the large neutral amino acids (LNAAs) tryptophan, tyrosine, leucine, valine, phenylalanine, and leucine were determined at 10 min before and 60 min after the injection. Bulimic subjects were found to report more symptoms of distressed mood throughout the entire monitoring period than controls. Five minutes following glucose ingestion the self-reports of depression, fatigue, anxiety, and bewilderment rose to a level among the bulimic subjects that was above that at baseline, and was higher than that of bulimia nervosa (BN) subjects receiving placebo. No comparable change in mood was observed among controls. Blood glucose levels were correlated with mood in the bulimic group, but not in controls. In addition, the glucose injection induced a heightened urge to binge in the bulimic group (compared to placebo at 10 and 60 min), whereas reducing food cravings (for sweets) in the controls (at 5 min). When collapsed across time and injection condition, the blood glucose level of bulimics was lower than that of controls. There were no differences in insulin response between the groups. The bulimic group was found to have lower baseline levels of blood tryptophan, whereas no differences in the tryptophan/LNAA ratio were observed either at baseline or following glucose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448265 TI - Enhanced processing of an aversive memory following inescapable shock in rats. AB - The aim of the present study was to determine the effect of inescapable shock on appetitive and aversive memory retrieval. Rats conditioned in a T-maze with appetitive (10% sucrose) and aversive (2.0 mA) events were subjected, respectively, to inescapable, escapable, and no-shock stress treatments. A retention test conducted 48 hr following exposure to stress treatments showed an enhanced avoidance behavior to enter a previously shocked goalbox with the absence of such a difference in responding to the nonshocked goalbox by the animals exposed to inescapable footshock stress. This differential response was not observed in two other groups, one given escapable footshock and the other no shock at all. This finding suggests memory processing is selectively enhanced in the helplessness condition and parallel to the retrieval bias that is evidenced in humans in depressive mood and induced helplessness. PMID- 8448266 TI - Development of tolerance after repeated administration of a selective muscarinic M1 antagonist biperiden in healthy human volunteers. AB - The muscarinic antagonist biperiden produces a dose-dependent inhibition of (REM) sleep on acute administration. The present study addressed the possibility of pharmacological tolerance after repeated biperiden administration. Six healthy volunteers were studied under sleep laboratory conditions in the following situations: one acclimatization, night, two baseline (that were averaged), 4 nights of biperiden administration, and 4 nights of placebo recovery administration. Six milligrams of biperiden and placebo were administered in identical capsules. Volunteers and technicians were blind to the order of the administration of the capsules. REM sleep time was reduced during the first and the second night, but was not significantly different in comparison with baseline by the third night. During placebo recovery nights, REM sleep time was not different from baseline. REM sleep latency was increased during the first and second nights of biperiden administration, but tolerance to this effect was observed by the third night. On placebo nights a dramatic shortening of REM latency was observed. The present findings support the hypothesis that anticholinergic drugs, even a selective M1 antagonist such as biperiden, induce tolerance soon after administration. A similar effect has been reported with scopolamine, a nonselective muscarinic antagonist, but the main difference is that biperiden withdrawal was not followed by an REM sleep rebound. The observed effect on REM sleep latency during placebo administration may be related to a supersensitivity to muscarinic M-1 receptors that trigger the first REM sleep period. Because short REM latency has been the main finding in the sleep of depressed patients, some implications of the present findings are discussed. PMID- 8448267 TI - Circannual and menstrual rhythm characteristics in manic episodes and body temperature. AB - Most reports in the literature deal with groups when summarizing the timing of affective disorders along the scale of the year and the menstrual cycle. In order to look for any regularity in timing of manic episodes in a single individual along these two time scales, a woman with a history of mania only, caused by schizoaffective disorder and on maintenance therapy with thioridazine hydrochloride self-measured basal body temperature daily and recorded onset and duration of manic episodes for 11 years. Statistically significant rhythms were found in body temperature with periods equal to the menstrual cycle and the year, with acrophase (highest values) during the luteal phase and winter, respectively. The timing of 11 manic episodes was not random but occurred during distinct portions of the menstrual cycle and the year. Most manic days occurred near menstruation or during the follicular phase of the menstrual cycle (up to ovulation) and between December and May (winter-spring). A temporal schedule for psychopharmacological treatment designed from individualized, longitudinal records that adjusts daily dosages according to both time of year and stage of menstrual cycle might alleviate or minimize the occurrence, magnitude and/or duration of mania and possibly other affective disorders that are found to be associated with underlying biological periodicities. PMID- 8448268 TI - MRI subcortical signal hyperintensities in mania at first hospitalization. PMID- 8448269 TI - Variation in symptom severity over the menstrual cycle of schizophrenics. PMID- 8448270 TI - Dysthymia characteristic of heavy alcohol use in depressed adolescents. PMID- 8448271 TI - Bipolar spectrum disorder and fragile X syndrome: a family study. PMID- 8448272 TI - Caffeine potentiation of taste in panic-disorder patients. PMID- 8448273 TI - Adjunctive yohimbine for treatment in refractory depression. PMID- 8448274 TI - Urinary quantification of drugs. PMID- 8448275 TI - Black male physicians at risk. PMID- 8448276 TI - Factors related to the keeping of appointments by indigent clients. AB - Few recent studies address how situational variables and the characteristics of clients and organizations predict whether indigent clients will keep medical appointments. In this study at a southern urban charity hospital, lack of transportation was a main reason given for not keeping the last appointment at an internal medicine clinic. In contrast, clients who kept their last appointment had higher incomes; had visited the facility for pain, infection, or follow-up after hospitalization; and had been referred to the clinic less than two weeks before their appointment. Overall, whether appointments were kept or broken seemed to depend on the recency of medical attention and the perceived severity of a problem. Implementation of a system-wide discharge-planning system resulted in fewer broken appointments. Perceived communication difficulties with clinic personnel and long waits were important predictors of overall utilization. Decentralizing care through community health clinics and adopting a more holistic approach to care may improve utilization of health care facilities. PMID- 8448277 TI - Neurological impairment among elderly African-American nursing home residents. AB - In this pilot study, 288 elderly African-American and 482 white residents of 10 nursing homes in Wayne County, Michigan, were compared for neurological impairment. The frequency of diagnosis of neurological impairment was equivalent for African-American and white males, but greater for African-American females than for white females. Cerebral vascular accident (CVA, or stroke) and nonspecific dementia were the most common neurological diagnoses for all groups. For males but not females, there was a statistically significant difference in the causes of neurological impairment, with more African-Americans diagnosed as having CVA, and more whites diagnosed as having nonspecific dementia. While the incidence of neurological impairment in African-Americans exceeded that of whites, predominantly white nursing homes offered more sophisticated care. This suggests the need to review the means by which comprehensive nursing home care may be expanded in the African-American community. PMID- 8448278 TI - Findings from a demonstration outreach project at a community health center. AB - Outreach using personal contact was a cornerstone of the federally funded Community Health Center (CHC) movement of the 1960s. Funding cuts and changes in federal policy have led to the discontinuation of this activity in most CHCs. This paper assesses aspects of a demonstration outreach project designed to encourage use of a CHC in Orangeburg, South Carolina. The evaluation shows that this type of outreach effort, which includes door-to-door canvassing, can identify specific needs for primary health care services in a poor underserved community, and can enhance community access to Medicaid, although the financial impact of bringing poor patients into CHCs by means of this type of outreach is relatively low. PMID- 8448279 TI - Our future is in jeopardy: the mental health of Native American adolescents. AB - The incidence of emotional disorders and mental illness among Native American adolescents is strikingly high. Yet despite promises of support from the federal government, the mental health resources available among Indian communities are negligible and must be expanded. Two federal laws--the Indian Health Care Amendments of 1990, and the Indian Health Care Amendments of 1992--help address this problem, including the integration of community health services into schools, the development of innovative mental and physical health programs for Native American youth, and the recruitment of more health professionals into Native American communities. PMID- 8448280 TI - Increasing obstetrical care access to the rural poor. AB - Rising malpractice insurance rates have led to a decrease in the number of physicians who provide rural obstetrical care. North Carolina has responded with the Rural Obstetrical Care Incentive (ROCI) Program, which provides up to $6,500 per year to physicians who provide obstetrical care to the rural poor in conjunction with a local health department. This study finds some evidence that the program has led to an increase in the satisfaction that physician participants feel toward the prenatal care available at the local health department; that participants are increasing their provision of obstetrical care to Medicaid patients compared to other physicians in the state; and that the percentage of women delivering after receiving inadequate prenatal care is decreasing in the original ROCI counties, at a time when other rural counties are experiencing an increase in this measure. Other states should consider the ROCI program as one aspect of a rural health strategy. PMID- 8448281 TI - Treatment of opportunistic fungal infections. PMID- 8448282 TI - Decline of clinical hepatitis B in workers at a general hospital: relation to increasing vaccine-induced immunity. AB - Hepatitis B is a well-recognized occupational hazard of health-care workers that can be prevented with vaccination. However, because data on the current epidemiology of hepatitis B virus (HBV) in this population are limited, no consensus exists regarding the requirement for immunization. In 1980-1989, 4,908 exposures of health-care workers to patients' blood and/or other body fluids were reported and evaluated at a general hospital. During this period, 4.8% of patients to whom health-care workers were exposed were positive for hepatitis B surface antigen (HBsAg). In exposed workers, the rate of protective immunity to HBV (measured by antibody to HBsAg) increased from 14% in 1980 to 55% in 1989. Hepatitis B vaccine became available at this hospital in 1983. The increase in antibody to HBsAg was not associated with an increase in antibody to HBV core antigen; this finding suggests that the increase in immunity was primarily vaccine induced. The incidence of reported clinical hepatitis B in health-care workers decreased from 82/100,000 in 1980-1984 to zero in 1985-1989 (odds ratio = 20.06; P = .0012). Thus, in this study, a program of hepatitis B immunization for health-care workers was associated with a significant decline in clinical HBV infection despite continued exposure to patients positive for HBsAg. PMID- 8448283 TI - Clinical spectrum of nonmenstrual toxic shock syndrome (TSS): comparison with menstrual TSS by multivariate discriminant analyses. AB - To further characterize the clinical spectrum of nonmenstrual toxic shock syndrome (NMTSS), we constrasted and compared the clinical and laboratory features of 24 patients with NMTSS with those of 21 patients with menstrual TSS (MTSS), using univariate and stepwise discriminant analyses. In contrast to patients with MTSS, those with NMTSS comprised a heterogeneous group with varying host factors and clinical presentations. The NMTSS group differed from the MTSS group in terms of the frequency of prior antimicrobial treatment (46% vs. 16%; P = .05), the rate of nosocomial acquisition (65% vs. 0; P = .0001), and the time of onset of fever and rash in relation to the initial symptoms (P = .005 and .03, respectively, with earlier onset in the NMTSS group). In addition, NMTSS patients experienced more frequent renal and CNS complications and less frequent musculoskeletal involvement (P = .07 in all three cases). Stepwise discriminant analysis identified four variables (delayed onset of TSS symptoms after precipitating injury or event, more frequent CNS manifestations, less frequent musculoskeletal involvement, and higher degree of anemia) differentiating NMTSS patients from MTSS produced TSS toxin 1 (TSST-1) with comparable frequency (62% vs. 84%; P = .2), but production of staphylococcal enterotoxin A (SEA) was less common in NMTSS than in MTSS (33% vs. 74%; P = .01). Furthermore, MTSS-associated isolates more commonly coexpressed TSST-1 and SEA than did NMTSS-associated isolates (68% vs. 28%; P = .01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448284 TI - Disseminated atypical blastomycosis in two patients with AIDS. AB - Two men with AIDS developed fungal infections and subsequently died as a result of dissemination of the fungal infection. Findings obtained by histologic examination, serological studies, and cultures suggested that the infections were caused by Blastomyces dermatitidis. Tissue sections showed polymorphic yeast-like cells 5-20 microns in diameter (some with broad and others with narrow single- or multiple-based buds), small yeasts, and hyphal elements. The exoantigen K positivity and exoantigen A negativity of one of the isolates indicated that the fungus was more like an African than a North American serotype. PMID- 8448285 TI - Agrobacterium infections in humans: experience at one hospital and review. AB - Agrobacteria are noted primarily for their phytopathogenicity and when isolated from human clinical specimens are often considered contaminants or organisms of low pathogenicity. We report six cases at one hospital over a 6 1/2-year period in which infection was accompanied by a compatible clinical syndrome and review 19 cases reported in the literature. Fourteen of the 25 combined cases involved central venous catheter-associated infections. Six cases involved peritonitis, five of which occurred in patients undergoing continuous ambulatory peritoneal dialysis. Additional infections included two non-catheter-associated bacteremias, one prosthetic valve endocarditis, and two urinary tract infections. Most infections were community acquired, and restriction enzyme analysis of Agrobacterium isolates from eight patients at one hospital revealed unique patterns in each case without evidence for clonal dissemination of these strains. Agrobacterium isolates may be resistant to multiple antibiotics, and optimal therapy has not yet been determined. Agrobacteria should be recognized as opportunistic pathogens in the immunocompromised host, particularly in those with indwelling plastic catheters. PMID- 8448286 TI - Fatal disseminated infection with Aspergillus terreus in immunocompromised hosts. AB - Aspergillus terreus is widespread in the environment but only uncommonly infects humans. It can cause cutaneous and subcutaneous infections, and several cases of local invasive disease have been reported; to our knowledge, however, only five cases of disseminated disease have been documented previously. We describe here four additional patients with disseminated disease caused by A. terreus. All four had an underlying hematologic or lymphoreticular malignancy, were immunocompromised secondary to prolonged neutropenia or immunosuppressive therapy, and had invasive pulmonary disease (a circumstance supporting a respiratory route of infection). Despite treatment with amphotericin B, all four patients died. When recovered from clinical specimens, A. terreus should not routinely be dismissed as a saprobe, particularly in immunocompromised hosts. PMID- 8448287 TI - Treatment of Strongyloides stercoralis hyperinfection syndrome with thiabendazole administered per rectum. AB - There is a rising interest in Strongyloides stercoralis infection due to the expanding population of immunosuppressed patients. Currently the drug of choice for both enteric and tissue forms of infection with this organism is oral thiabendazole. We report a patient with a small bowel obstruction due to S. stercoralis hyperinfection who was unable to take thiabendazole orally. Thiabendazole was administered rectally, and the hyperinfection syndrome resolved. Peak serum concentrations of thiabendazole were achieved 4 hours after rectal administration, and drug levels were sustained longer than previously reported with oral dosing. In addition, elevated levels of thiabendazole metabolites in the patient's urine further confirmed significant absorption. Rectal administration of thiabendazole should be considered for patients unable to take the medication orally. PMID- 8448288 TI - Malaria during pregnancy: neonatal morbidity and mortality and the efficacy of chloroquine chemoprophylaxis. AB - In malaria-endemic regions, the impact of malaria upon pregnancy and the value of chemoprophylaxis for malaria for pregnant women remain controversial. We prospectively studied 302 pregnant women who presented in labor to Centre Medical Evangelique, Nyankunde, Zaire. We evaluated the incidence of malarial infection in mothers, placentas, and neonates and examined the effect of infection on birth weight and perinatal mortality. We analyzed the outcome of pregnancy in relation to prophylaxis with chloroquine, controlling for parity and prenatal clinic attendance. Peripartum smears of maternal blood (21%), placentas (33%), cord blood (9%), and neonatal blood (7%) were positive for Plasmodium falciparum. Maternal malaria increased the risk of perinatal death (relative risk [RR] = 12.4) and low birth weight (RR = 3.7). Neonatal malaria increased the risk of perinatal death (RR = 7.2). Chloroquine prophylaxis protected against maternal (RR = 0.4) and fetal malaria (RR = 0.2), low birth weight (RR = 0.39), and perinatal death (RR = 0.38). Peripartum malaria increases the risk of perinatal death and low birth weight. Chemoprophylaxis with chloroquine during pregnancy may have a protective effect, even in certain areas where chloroquine-resistant P. falciparum is endemic. PMID- 8448289 TI - Tongue abscess: case report and review. AB - Tongue abscesses are extremely rare infections despite the relatively frequent exposure of the tongue to bite trauma during mastication and seizures. We describe a case of tongue abscess in a 40-year-old man and discuss the pathophysiology, diagnosis, and treatment of this entity. PMID- 8448290 TI - Clinical characteristics of seven cases of diarrhea associated with a novel acid fast organism in the stool. AB - In the last 4 years, we have identified an acid-fast, autofluorescent organism in the stool of seven patients with diarrhea. The organism was identified as a cyanobacterium-like organism by the Centers for Disease Control (Atlanta) and as a coccidian by researchers in Peru and at the University of Arizona (Tucson). We present reports on the seven cases and a review of the literature. Three patients were known to be seropositive for the human immunodeficiency virus (HIV). All complained of watery diarrhea that had begun 3 days to 8 months before presentation. Colonoscopy in two patients showed a normal mucosal pattern; a biopsy for one of these patients showed chronic nonspecific inflammation of the colon. Examination of stool for ova and parasites revealed multiple oval and round nonrefractile organisms with well-defined walls that resembled large cryptosporidia; they measured 8-9 microns in diameter. These organisms did not stain by Giemsa or gram methods but were acid-fast by Kinyoun carbolfuchsin and Ziehl-Neelsen stains. The organisms fluoresced as blue under ultraviolet light. In the immunocompetent patients, diarrhea lasted an average of 19 days and resolved spontaneously. Diarrhea persisted in the HIV-seropositive patients. The clinical course and organism resembled those reported for travelers and HIV seropositive patients. This organism may represent a newly identified cause of watery diarrhea in humans. PMID- 8448291 TI - Ventricular CSF shunt infections associated with Corynebacterium jeikeium: report of three cases and review. AB - Ventricular CSF shunt infections due to Corynebacterium jeikeium are rare. Such infections may become manifest weeks to months after surgery. They are difficult to eradicate and often recur. We report three cases of C. jeikeium ventricular CSF shunt infections, all of which occurred in patients who received long-term prophylactic therapy with antibiotics and had protracted hospitalizations. Two patients had multiple recurrences, and all patients required shunt revision. Additional therapy with intrathecal vancomycin for 6-10 days after surgery was effective for this unusual cause of ventricular CSF shunt infection. On the basis of our experience and a review of six previously published case reports, we recommend CSF sterilization with intravenous and intrathecal vancomycin, followed by replacement of shunt hardware. PMID- 8448292 TI - The enigma of candiduria: evolution of bladder irrigation with amphotericin B for management--from Anecdote to Dogma and a lesson from Machiavelli. AB - Candiduria has emerged as a common, vexing diagnostic and therapeutic problem over the past 40 years. Treatment by means of bladder irrigation with a solution of amphotericin B has become widely used in clinical practice. However, the specifics of the procedure--concentration of amphotericin B, use of continuous washing vs. instillation with cross-clamping to allow "dwell-times," and duration of treatment--are based entirely on anecdotal experiences. The published reports and evolution of recommendations are reviewed. A prospective randomized double blind study is needed to provide answers. In the meantime, administration of 200 300 mL of amphotericin B solution by triple-lumen urethral catheter with cross clamping for 60-90 minutes seems most appropriate. Irrigation for no longer than 2 days should suffice if the procedure is to be effective. The optimal concentration of amphotericin B has not been defined; however, 5-10 mg/L appears adequate. PMID- 8448293 TI - Catheter-related Fusarium solani fungemia and pulmonary infection in a patient with leukemia in remission. AB - Members of the genus Fusarium are ubiquitous fungi uncommonly associated with infection. Disseminated fusariosis typically occurs in neutropenic hosts and carries a high mortality rate. We present a case of disseminated fusariosis that is unique in terms of its relative lack of symptomatology despite documentation of fungemia and pulmonary nodules. A summary of the literature is also presented. PMID- 8448294 TI - Myositis due to Pleistophora (Microsporidia) in a patient with AIDS. AB - Microsporidia are obligate intracellular protozoa that parasitize both vertebrates and invertebrates and are now recognized as important pathogens in individuals infected with human immunodeficiency virus type 1 (HIV-1). We describe the clinical and morphological features of a case of pleistophora (microsporidian) myositis in a patient with AIDS and delineate the stages of the microsporidian life cycle, as visualized by light and electron microscopy. We discuss significant aspects of microsporidian infections in humans and of myopathy attributable to other causes in HIV-1-infected individuals. As far as we know, ours is only the second reported case of microsporidian myositis and the first reported case in a patient with documented HIV-1 infection. PMID- 8448295 TI - Duration and efficacy of immune response to hepatitis B vaccine in high-risk Chinese adolescents. AB - The long-term immunogenicity and protection provided by a plasma-derived hepatitis B vaccine was determined in a cohort of susceptible Chinese adolescents who were immunized in 1986. Ninety-five children, aged 13 to 15 years, received three vaccine doses (at 0, 1, and 2 months), and during subsequent annual follow ups for 5 years, their serological markers for hepatitis B virus and levels of alanine aminotransferase were determined. After the primary vaccine series, 94 subjects (99%) developed antibody to hepatitis B surface antigen (anti-HBs). At the 60-month follow-up, 73% of vaccinees still had levels of antibody at or above 10 mIU/mL, which is considered the protective level. Nine vaccine responders (9%) developed antibody to hepatitis B core antigen, and in eight of these individuals, levels of anti-HBs increased transiently. None of the adolescents developed detectable levels of hepatitis B surface antigen or clinical hepatitis. Immunization of high-risk adolescents with a plasma-derived hepatitis B vaccine can induce long-lasting protective immunity that can prevent or modify primary infection for at least 5 years. Immunization with booster doses is not necessary during this period. PMID- 8448296 TI - Paralysis by ticks. 1922. PMID- 8448297 TI - Disseminated infection due to Acremonium species in a patient with Addison's disease. PMID- 8448298 TI - Hepatic and pulmonary pneumocystosis during primary prophylaxis for Pneumocystis carinii pneumonia with dapsone/pyrimethamine. PMID- 8448299 TI - Mediastinitis due to multiple resistant Corynebacterium xerosis. PMID- 8448300 TI - Association between Eikenella corrodens and streptococci. PMID- 8448301 TI - Why did infection with Aeromonas hydrophila occur when water contains so many other microorganisms? PMID- 8448302 TI - Use of gentamicin for treatment of enterococcal infections. PMID- 8448303 TI - A severe systemic reaction to trimethoprim-sulfamethoxazole in a patient infected with the human immunodeficiency virus. PMID- 8448304 TI - A severe hypersensitive reaction to trimethoprim-sulfamethoxazole in a patient infected with human immunodeficiency virus. PMID- 8448305 TI - Unusual manifestations of miliary tuberculosis: cutaneous lesions, phalanx osteomyelitis, and paradoxical expansion of tenosynovitis. PMID- 8448306 TI - Facial palsy, meningococcal meningitis, and reactivation of herpes simplex virus. PMID- 8448307 TI - Cure of Rhizopus sinusitis in a liver transplant recipient with liposomal amphotericin B. PMID- 8448308 TI - Endocarditis due to Neisseria mucosa. PMID- 8448309 TI - Use of mefloquine for malarial chemoprophylaxis in its first year of availability in the United States. PMID- 8448310 TI - Magnetic resonance imaging in listerial brain stem encephalitis. PMID- 8448311 TI - Pulmonary T-cell lymphoma in a patient with the acquired immunodeficiency syndrome. PMID- 8448312 TI - Oral ciprofloxacin therapy for Bacillus cereus wound infection and bacteremia. PMID- 8448313 TI - Acute abdominal pain as a presenting symptom of varicella-zoster virus infection in recipients of bone marrow transplants. PMID- 8448314 TI - Intramuscular pentamidine for the prevention of Pneumocystis carinii pneumonia in patients infected with human immunodeficiency virus. AB - We retrospectively reviewed the charts of 96 patients infected with human immunodeficiency virus (HIV) who received intramuscular pentamidine for the prevention of Pneumocystis carinii pneumonia (PCP). These patients, all of whom had either a history of PCP or a CD4 lymphocyte count of < or = 0.2 x 10(9)/L, were intolerant of sulfa drugs, neutropenic, or intolerant of aerosolized treatment. Intramuscular pentamidine was given monthly by the Z-track technique at a dosage of 300 mg (4 mg/kg if the patient weighed < 50 kg). During a total of 350 months of primary prophylaxis in 47 patients and 426 months of secondary prophylaxis in 49 patients, only three cases of PCP occurred. More than 73% of the patients were receiving zidovudine concomitantly. Adverse reactions to intramuscular pentamidine included two episodes of hypotension, three of sterile abscess, two of glucose intolerance, and one of asymptomatic hypoglycemia. The administration of intramuscular pentamidine by the Z-track technique for PCP prophylaxis appears to be highly effective and minimally toxic. PMID- 8448315 TI - Infected urachal remnants in the adult: case report and review. AB - Abnormalities of the urachus in adults are uncommon. Urachal tract remnants that abnormally remain patent are subject to infection. Urachal infection is frequently confused with a wide spectrum of midline intraabdominal or pelvic inflammatory disorders. Because the literature on urachal infection is primarily limited to articles in urology and surgical specialty journals, many physicians may not be familiar with the varied clinical manifestations. We describe a case of infection of a patent urachus in an adult and review the embryology and anatomy of the urachus as it relates to clinical presentation, evaluation, and management. Infection of a urachal remnant should be included in the broad differential diagnosis of omphalitis and midline abdominal or pelvic infections. Rarely, it may be a cause of recurrent urinary tract infection. Definitive management consists of surgical excision after the institution of antimicrobial therapy. PMID- 8448316 TI - Curvularia lunata endocarditis treated with terbinafine: case report. AB - A 44-year-old man developed endocarditis due to Curvularia lunata on a Carpentier Edwards porcine heterograft with clinical involvement of the ring of the aortic valve and the aortic root. Because curative surgery was considered to be extremely high risk, he was treated with antifungal drugs for nearly 7 years. Initial treatment with amphotericin B and ketoconazole was followed by long-term treatment with terbinafine, an experimental allyamine derivative. No adverse effects were attributed to terbinafine. At surgery nearly 7 years later, the aortic valve ring and aortic root appeared to be uninvolved, and the valve was replaced uneventfully. To our knowledge, this is the first report of successful treatment of curvularia endocarditis. PMID- 8448317 TI - Clinical gnathostomiasis: case report and review of the English-language literature. AB - Human gnathostomiasis is most frequently caused by the nematode Gnathostoma spinigerum. This disease is endemic to Southeast Asia, particularly Thailand and Japan. The clinical presentation is most commonly characterized by localized, intermittent, migratory swellings of the skin and subcutaneous tissues, often in association with localized pain, pruritus, and erythema. Since this worm can migrate to deeper tissues, any organ system may become involved. Characteristically, patients with gnathostomiasis have a moderate to severe elevation of the peripheral eosinophil count, with values not uncommonly exceeding 50% of the total white blood cell count. With modern-day travel and immigration, cases of gnathostomiasis are being diagnosed with increased frequency in the United States. Because of its rarity in this country, however, gnathostomiasis often is not included in an initial differential diagnosis despite the characteristic triad of intermittent migratory swelling, a history of travel to Southeast Asia, and eosinophilia. We report a case of cutaneous gnathostomiasis diagnosed in the United States, and we present a clinical review of the English-language literature on human gnathostomiasis. PMID- 8448318 TI - Cellulitis caused by Legionella pneumophila. AB - A patient with lymphoma presented with pneumonia. While receiving antibiotics, he developed a rapidly spreading cellulitis. The soft tissues were debrided in the operating room, and pathological examination showed fat necrosis and a fibrinopurulent exudate in the fibroadipose tissue; direct immunofluorescence of the debrided tissue revealed the presence of Legionella pneumophila. Culture of the specimen obtained during the operation yielded L. pneumophila. To our knowledge, this represents the first case report of cellulitis due to L. pneumophila. PMID- 8448319 TI - Blastomycosis in transplant recipients: report of a case and review. AB - Fungi cause serious, often fatal infections in immunocompromised hosts. Recipients of solid organ and bone marrow transplants are predisposed to invasive fungal infections with Candida species, Aspergillus species, and Cryptococcus neoformans. In contrast, infections with Blastomyces dermatitidis have rarely been diagnosed in transplant recipients. We describe a patient who received an orthotopic heart transplant and developed recurrent disseminated blastomycosis. Other reported cases of blastomycosis in transplant recipients are summarized. Clinical presentation, treatment options, and morbidity associated with infections with B. dermatitidis in transplant patients are reviewed. PMID- 8448320 TI - Fatal respiratory disease due to Corynebacterium diphtheriae: case report and review of guidelines for management, investigation, and control. AB - Dramatic reductions in the incidence of diphtheria and high levels of childhood vaccination in recent decades have led the United States to establish the goal of diphtheria elimination among persons < or = 25 years of age by the year 2000. In 1990, an unimmunized 25-month-old child died of respiratory diphtheria in Dade County, Florida, before treatment with diphtheria antitoxin could be instituted. Twenty-three asymptomatic household contacts and other close contacts of the child were identified, cultured for Corynebacterium diphtheriae, given antimicrobial prophylaxis, and vaccinated with diphtheria toxoid when indicated. Three contacts (13%) had pharyngeal cultures positive for toxigenic C. diphtheriae of the same type as that causing infection in the deceased child, but no additional cases developed. Although the source of infection was not determined, three other close contacts had recently been to Haiti, where diphtheria is endemic. A serological survey of 396 children < 5 years of age who received care at a medical center in Dade County revealed that 22% lacked protective immunity to diphtheria. Attainment of the goal of diphtheria elimination among persons < or = 25 years of age--and ultimately among all persons--will depend on the maintenance of a high level of clinical awareness of the disease, the prompt institution of preventive measures among close contacts of patients with sporadic cases, and improved vaccination levels among infants, children, and adults. PMID- 8448321 TI - Aeromonas hydrophila infections of skin and soft tissue: report of 11 cases and review. AB - We report the clinical and microbiological characteristics of 11 cases of Aeromonas hydrophila infection of skin and soft tissue, and we review the English language literature on such infections. Of our 11 patients, seven (64%) presented to the hospital between the months of May and September (inclusive). Three patients (27%) had an underlying systemic illness, and two (18%) had nosocomially acquired infection. The nine patients with community-acquired infection had all experienced antecedent trauma, and seven (78%) of these nine reported recent exposure to freshwater. All patients had clinical evidence of soft-tissue inflammation, and nine (82%) had fever. Four wounds were characterized by a foul odor. The infection was polymicrobial in nine cases (82%). Treatment included the administration of antibiotics in nine instances, but empirical antimicrobial therapy provided coverage against Aeromonas in only two cases. Ten patients required surgical management of their wounds. Posttraumatic wound infections with a history of freshwater exposure should alert the clinician to the possible presence of A. hydrophila. Prompt surgical evaluation of wounds in combination with appropriate antibiotic therapy is recommended for the management of these infections. PMID- 8448322 TI - Colonization and cross-colonization of nursing home patients with trimethoprim resistant gram-negative bacilli. AB - A prospective study of 67 patients in a nursing home and a subpopulation of 31 patients who were stratified according to functional level--a general measure of the amount of nursing care required by the patients--was performed. The goals of this study were (1) to determine whether antibiotic selection of resistant variants from within endogenous flora of hosts or horizontal transmission is more important in the development of colonization with trimethoprim-resistant gram negative bacilli (TRGNB) in a nursing home; (2) to identify the mode(s) of transmission if horizontal transmission is more important; and (3) to identify risk factors for colonization and cross-colonization with TRGNB. Although a number of variables were associated with colonization, only a decreased functional level appeared to be independently associated with colonization. Isolates from the subpopulation were subtyped by restriction endonuclease digestion of cellular DNA, as were isolates from personnel of the nursing home. Results revealed that 16 of 21 staff members had 48 positive cultures for TRGNB. Of 25 typeable isolates, 12 from seven of the 21 staff members were identical to patient strains. Analysis of acquisition of new strains of TRGNB by members of the subpopulation showed that 67.5% were the result of cross-colonization. Our data are consistent with, but do not prove, the hypothesis that nurses' hands are the primary mode of transmission of TRGNB in this nursing home and suggest that most colonization could be prevented by interdicting horizontal transmission. PMID- 8448323 TI - Molecular analysis of multiply recurrent meningitis due to Escherichia coli K1 in an infant. AB - Bacterial DNA polymorphism was used to document the occurrence of three separate episodes of meningitis caused by Escherichia coli K1 in an infant. The methods employed included determination of the restriction fragment length polymorphism of total DNA and of ribosomal DNA regions as well as DNA fingerprinting by the arbitrarily primed polymerase chain reaction. By these three genotypic approaches, the three isolates obtained from the infant's cerebrospinal fluid on days 9, 34, and 70, respectively, were found to share the same patterns, which were different from the patterns of control strains. Thus, these three episodes of E. coli K1 meningitis were due to a single strain. DNA-based typing techniques seem extremely promising as tools to be used in unraveling the complex mechanisms of recurrent meningitis. PMID- 8448324 TI - Vaginitis due to Saccharomyces cerevisiae: epidemiology, clinical aspects, and therapy. AB - Vaginitis due to Saccharomyces species is extremely rare. Nine patients with 20 vaginal isolates of Saccharomyces cerevisiae who presented with either asymptomatic vaginal colonization or symptomatic vaginitis indistinguishable from that caused by Candida albicans are described. All patients had a history of chronic or recurrent vaginitis, and all but two had systemic or local predisposing factors. In vitro tests of antimycotic sensitivity revealed reduced susceptibility of S. cerevisiae to the majority of available azole agents, with outright resistance to fluconazole. In accordance with these findings, the clinical response to conventional topical and oral antimycotic drugs was frequently suboptimal and incomplete. Electrophoretic karyotyping of strains revealed several distinct types of S. cerevisiae; this information permitted both longitudinal follow-up and differentiation of relapse from reinfection. In three patients with recurrent vaginitis, a unique epidemiological relationship was documented between S. cerevisiae and Torulopsis glabrata, another unusual and resistant vaginal pathogen. Isolation of S. cerevisiae from the vagina of symptomatic patients should not be ignored; treatment of vaginal infection with this yeast requires selected, often prolonged therapy. PMID- 8448325 TI - [Hypercholesterolemic effect of unsaturated fatty acids]. PMID- 8448326 TI - [Morphologic and functional heart changes in a group of healthy elderly individuals aged 70 years and over]. AB - BACKGROUND. The increasing age of the population, makes necessary to have "normal values" in order to make diagnosis and treatment in this population group. The purpose of this study is to determine the morphological and functional changes in a group of healthy aged above 70 years. METHODS: We studied 125 subjects older than 70 years, mean of 74.9 and 50 healthy aged 9-45, with a mean of 25.8, who served as control group. Twenty-five were excluded by history, chest X-Ray, ECG and Echocardiogram because cardiac disease. An echocardiographic M and 2D and pulsed Doppler study, was done to obtained several morphological and systolic and diastolic function parameters. A good quality echo to measure morphologic and systolic function was obtained in 69 study group patients. In all study and control group, was obtained a good quality mitral flow signal to measure diastolic function. PMID- 8448327 TI - [Pseudohypoparathyroidism: a familial case]. AB - The pseudohypoparathyroidism is a rare disease which progresses with hypocalcemia despite the high levels of PTH. Clinically, there are three different types of pseudohypoparathyroidism, depending on the urinary elimination of AMPc, the presence of Albright's osteodystrophy and the response to exogenous PTH. It is detected occasionally, as it was the case of the family that we present here, in which 6 of the 9 members from the two last generations were affected by this entity. PMID- 8448328 TI - [Hematogenous pubic osteoarthritis]. AB - Pubic osteoarthritis is a little known pathological entity with a very controversial etiology. We present four cases of public osteoarthritis in which the infectious etiology was hematogeneous. The causal germs were: Staphilococcus aureus, Pseudomona aeruginosa, Mycobacterium tuberculosis and Brucella melitensis. In the first three cases, a surgical approach was used, allowing us to establish the etiological diagnosis of the process and to perform the local debridement. In the case of brucellar etiology, an isolated medical treatment was applied, according to the therapeutical guidelines recommended for brucellar bone infections. We have not observed recurrence of the septic process in any of the four cases, with a follow-up period ranging from one to three years. PMID- 8448329 TI - [Occult thyroid carcinoma: presentation of 2 new cases]. AB - We report two cases of occult neoplastic of Thyroids. Normal clinics analysis and eco. The diagnosis was made by punction-aspiration and confirmed by pathological study after surgery we leave reviewed the literature about this pathology and we emphasize the importance of the thyroids in the research of hidden neoplasias. PMID- 8448330 TI - [Respiratory muscle involvement in systemic lupus erythematosus: retracted lung syndrome]. AB - We describe a case of the Syndrome of Retracted Lung (SRL), a very rare entity which is part of the respiratory pathology that may be seen in the Lupus Erithematosus Systemic (LES). Detailed clinical data are presented and general relevant aspects related to this type of lupidic manifestation are reviewed. PMID- 8448331 TI - [Aortic dissection: false negative results of aortography and thoracic CAT, report of a case]. AB - Acute dissection of the aorta is a relatively frequent clinical entity, with a poor prognosis and a global mortality of 40% during the first 48 hours. A correct diagnosis and an early surgical treatment may modify the natural course of the dissection of aorta. We present a case of a patient with high clinical suspicion in the aortography, thoraci CAT and transthoracic echocardiogram (TTE). However, it was not possible to establish the diagnosis. The transesophagic echocardiogram (TEE), on the contrary, suggested the presence of dissection of aorta, as was later verified in the necropsis methods, seems to support the TEE as the first election method in the dissection of aorta. PMID- 8448332 TI - [Lipid levels of a healthy population in the region of Extremadura]. AB - We present the results of the first epidemiological study on lipidic levels among a healthy population from Extremadura. The study included 1.128 subjects, 520 males and 608 females, distributed by age and sex. Average total cholesterol levels were 228 +/- 40 mg/dl among middle-age and 215.6 +/- 43 mg/dl among women. We observed a significant reduction of these figures in ages above 60. In addition, we observed significant differences in HDL-Ch levels between men and women from all ages, with higher values among women and we only observed significant differences regarding total cholesterol levels between men and women in the 20-29 and 40-49 age-groups. Total cholesterol levels were higher than 220 mg/dl in more than half the studied population between 40 and 60 years of age and higher than 250 mg/dl in 20% of the subjects in such age groups. These data suggest the need for dietary changes in near 70% of the population if cholesterol levels are to approach the recommendations of the Sociedad Espanola de Arteriosclerosis. PMID- 8448333 TI - [Left auricular myxoma and pulmonary hypertension]. PMID- 8448334 TI - [Pulmonary tuberculosis associated with pulmonary epidermoid carcinoma]. PMID- 8448335 TI - [Scientific humanism and clinical education]. PMID- 8448336 TI - [Leukocytoclastic vasculitis and neoplasm of the pancreas]. PMID- 8448337 TI - [Comparative study of 2 methods for the study of antibodies against Chlamydia trachomatis. Diagnostic usefulness]. PMID- 8448338 TI - [Levels of lipoprotein(a), other lipids and lipoproteins in adolescents from the health area of Alcoy]. AB - Several epidemiological and necroscopic evidences suggest that, despite that the ischemic cardiopathy (IC) can be generally detected only since the fourth decade of life, it starts during the first years of life and adolescence. We have studied 278 teen-agers, with 13-14 years of age, attending the 8th school year (primary education) in five schools of Alcoy. 117 were males and 161 females. Levels of lipoprotein (a) (Lp[a]), total cholesterol (TC), cholesterol linked to high density lipoproteins (C-HDL) and its subfractions (C-HDL2 and C-HDL3), triglycerides (TG), apoproteins A-I and B (Apo A and Apo B) were determined. Cholesterol linked to low density lipoproteins (C-LDL) was calculated using the Friedewald-Fredrickson's equation. Mean values and standard deviation were: Lp(a) = 29.99 +/- 33.61 mg/dl., TC = 160.4 +/- 25.4 mg/dl., C-HDL = 54.0 +/- 12.3 mg/dl., C-HDL2 = 8.7 +/- 6.5 mg/dl., C-HDL3 = 46.2 +/- 18.6 mg/dl., TG = 72.6 +/- 26.8 mg/dl., C-LDL = 91.6 +/- 22.0 mg/dl., Apo A = 136.4 +/- 24.2 mg/dl., Apo B = 60.7 +/- 21.7 mg/dl. 38% teen-agers had Lp(a) levels higher than 30 mg/dl., 7.5% had levels of TC higher than 200 mg/dl., 12.8% had levels of C-HDL equal or higher than 40 mg/dl. and 4.7% had levels of C-LDL equal or higher than 130 mg/dl. From our study, we can conclude that, despite that the levels of TC, C-LDL and C-HDL in these teen-agers are within relatively normal limits, there is a high percentage with levels of Lp(a) actually considered as a risk factor. PMID- 8448339 TI - Reactions of arsenic(III) and arsenic(V) species with glutathione. AB - Arsenic is metabolized by living systems using oxidation-reduction and methylation reactions, and reduced glutathione (GSH) has been shown to be important in that metabolism. In this study, the solution reactions between GSH and arsenate, arsenite, and their methylated metabolites, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), were characterized using 1H and 13C NMR under a nitrogen atmosphere. Binding to GSH through the thiol group was primarily followed by shifts in the carbon atom bonded to the sulfhydryl group of the cysteinyl residue, i.e., the CH2 carbon atom and the protons bonded to it. The methylated metabolites also showed shifts in the methyl groups attached to the arsenic atom after reaction with GSH. Sodium arsenite, As(III), bound to GSH to form an As(SG)3 complex in solution as indicated by NMR spectra. The identity of the complex was confirmed by FAB-MS after isolation of the compound. Mixtures of sodium arsenate, As(V), and GSH showed that arsenate oxidized GSH in D2O solutions at pH 7 to form oxidized glutathione (GSSG). When the molar ratio of As:GSH exceeded 1:2, evidence for the formation of As(SG)3 was observed. MMA and DMA are both As(V) species, and mixtures with GSH showed oxidation to GSSG initially followed by formation of CH3.As(SG)2 and (CH3)2.As.SG, respectively. The effects of GSH on arsenic metabolism may result from direct reactions between the two compounds. PMID- 8448340 TI - Determination of atrazine metabolites in human urine: development of a biomarker of exposure. AB - Enzyme-linked immunosorbent assays (ELISAs) are reported for the detection of atrazine and its principle metabolite in human urine. The ELISAs can be used with crude urine or following extraction and partial purification by methods described in this report. GC, MS, and HPLC techniques were used to confirm and complement the ELISA methods for qualitative and quantitative detection of urinary metabolites. A series of samples from workers applying this herbicide confirmed a mercapturic acid conjugate of atrazine as a major urinary metabolite. The mercapturate was found in concentrations at least 10 times that of any of the N dealkylated products or the parent compound. Atrazine mercapturic acid was isolated from urine using affinity extraction based upon a polyclonal antibody for hydroxy-s-triazines and yielded products sufficiently pure for structure confirmation by MS/MS. In a pilot study monitoring applicators, a relationship between cumulative dermal and inhalation exposure and total amount of atrazine equivalents excreted over a 10-day period was observed. On the basis of these data, we propose that an ELISA for the mercapturate of atrazine could be developed as a useful marker of exposure. PMID- 8448341 TI - Detection of the major DNA adducts of benzo[j]fluoranthene in mouse skin: nonclassical dihydrodiol epoxides. AB - Studies have demonstrated that the metabolic activation of benzo[j]fluoranthene (B[j]F) to a genotoxic agent proceeds through the formation of either the trans 4,5-dihydrodiol (B[j]F-4,5-diol) or the trans-9,10-dihydrodiol (B[j]F-9,10-diol) metabolite of B[j]F. Using 32P-postlabeling analysis, the profiles of DNA adducts formed in vivo in mouse skin from B[j]F-4,5-diol and B[j]F-9,10-diol were obtained to establish the contribution of each of these dihydrodiols to the formation of B[j]F-DNA adducts in vivo. B[j]F, B[j]F-4,5-diol and B[j]F-9,10-diol were applied to the shaved backs of mice (100 micrograms/mouse), and DNA adducts were isolated and separated using multidimensional TLC and reverse-phase HPLC. The greatest level of adducts was observed with B[j]F-4,5-diol, which resulted in the formation of 383 pmol of DNA adducts/mg of DNA. This level of DNA modification was more than 2 orders of magnitude greater than that observed with B[j]F or B[j]F-9,10-diol. The major adducts detected from the application of B[j]F-4,5-diol to mouse skin in vivo had chromatographic properties similar to those of the major adducts detected with B[j]F. In contrast, the major DNA adducts detected with B[j]F-9,10-diol had chromatographic properties distinctly different than the adducts formed from either B[j]F or B[j]F-4,5-diol. DNA adducts formed from the syn and anti isomers of the 4,5-dihydrodiol 6,6a-epoxide and the 9,10-dihydrodiol 11,12-epoxide of B[j]F were also evaluated. Each dihydrodiol epoxide derivative was reacted with calf thymus DNA in vitro and applied to mouse skin in vivo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448342 TI - Bis(hydroxyphenylethyl)deoxyguanosine adducts identified by [32P]-postlabeling and four-sector tandem mass spectrometry: unanticipated adducts formed upon treatment of DNA with styrene 7,8-oxide. AB - Calf thymus DNA was incubated with [8-14C]styrene oxide in vitro, and six covalent xenobiotic-DNA adducts were detected using the [32P]-postlabeling procedure. Adducts 1-3 were purified by HPLC and identified as bis-substituted-2' deoxyguanosine 3'-phosphate derivatives using four-sector tandem mass spectrometry. These adducts represented less than 2% of the total adducts detected by [14C]-radioactivity. Adducts 1-3 were also detected when styrene oxide was allowed to react with the mononucleotide, 2'-deoxyguanosine 3' phosphate only. The elemental compositions of these adducts (C26H30N5O9P) were determined by measurement of their accurate masses by high-resolution mass spectrometry and revealed the unusual incorporation of 2 mol of hydroxyphenylethyl moieties. The structures of these bis(phenylethyl) adducts were established by interpretation of high-energy collision-induced dissociation (CID) mass spectra, together with UV/visible and fluorescence spectrophotometry as N2-(2-hydroxy-1-phenylethyl)-O6-(2-hydroxy-2-phenylethyl)-2'-deoxygua nos ine 3'-phosphate (adduct 1), N2-(2-hydroxy-1-phenylethyl)-O6-(2-hydroxy-1 phenylethyl)-2'-deoxygua nos ine 3'-phosphate (adduct 2), and N1,N2-bis(2-hydroxy 1-phenylethyl)-2'-deoxyguanosine 3'-phosphate (adduct 3). The other most abundant adducts were detected only by [14C]-radioactivity and represented approximately 65% of the total covalent binding. These were identified as depurinated N7 substituted guanines by tandem mass spectrometry and UV/visible spectroscopy. The combination of advanced techniques of mass spectrometry with the [32P] postlabeling assay and spectroscopic techniques is a comprehensive strategy to assure complete structural identification of all xenobiotic-DNA adducts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448343 TI - Pyrrole formation from 4-hydroxynonenal and primary amines. AB - The reaction of trans-4-hydroxy-2-nonenal (4-HNE) with primary amines was investigated to elucidate chemistry that may clarify the nature of its physiological covalent binding with protein-based primary amino groups. Such binding of 4-HNE, generated endogenously from lipid peroxidation, appears to be a pathophysiologic factor in the modification of low-density lipoprotein and perhaps other instances. We now show that 4-HNE reacts with primary amines in aqueous acetonitrile at pH 7.8 to afford after workup, in 14-23% yield, the corresponding pyrroles, which were characterized by independent synthesis from 4 oxononanal. Additional, mostly unstable adducts are also formed, some of which eventually "age" to the pyrrole. Hydride reduction after initial adduct formation permits the isolation of more stable materials, one of which has been identified as the reduced amine Michael addition product. Pyrrole formation may constitute a physiologically important reaction of 4-hydroxyalkenals. PMID- 8448344 TI - Mechanisms and biological relevance of lipid peroxidation initiation. PMID- 8448345 TI - Reactions of the bioregulatory agent nitric oxide in oxygenated aqueous media: determination of the kinetics for oxidation and nitrosation by intermediates generated in the NO/O2 reaction. AB - The reaction kinetics of nitric oxide autoxidation in aerobic solutions were investigated by direct observation of the nitrite ion product and by trapping the strongly oxidizing and nitrosating intermediates formed in this reaction. The rate behavior observed for nitrite formation [rate = k3[O2][NO]2, k3 = (6 +/- 1.5) x 10(6) M-2 s-1 at 22 degrees C] was the same as found for oxidation of Fe(CN)6(4-) and of 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) and as for the nitrosation of sulfanilamide. There was a slight decrease in k3 to (3.5 +/- 0.7) x 10(6) M-2 s-1 at 37 degrees C. The second-order dependency for NO was observed at NO concentrations as low as 3 microM. The results of the competitive kinetics studies suggest that the key oxidizing intermediates, species which are both strong oxidants and nitrosating agents, are not one of those commonly proposed (NO2, N2O3, NO+, or O2NO-) but are one or more as yet uncharacterized NOx species. PMID- 8448346 TI - Kinetics of the postinhibitory reactions of acetylcholinesterase poisoned by chiral isomalathion: a surprising nonreactivation induced by the RP stereoisomers. AB - Inhibitory (ki), spontaneous (k0), and oxime-mediated reactivation (k(oxime)) reaction kinetics for the four stereoisomers of isomalathion (SPRC,SPSC,RPRC, and RPSC) were determined against rat brain acetylcholinesterase (AChE). (SPRC) Isomalathion was the most potent anticholinesterase agent and RPSC-isomalathion the least potent with racemic material approximately midway in activity. Following inhibition of rat brain AChE by (SPRC)- or (SPSC)-isomalathion, k0 and k(oxime) values were obtained that were comparable to (SP)-isoparathion methyl, indicating that the same mechanism of inhibition was shared, namely, formation of an O,S-dimethyl phosphorothiolated enzyme. Conversely, no appreciable reactivation occurred with or without oxime following inhibition of rat brain AChE by (RPSC)- or (RPRC)-isomalathion. This observation was not consistent with (RP)-isoparathion methyl, and a switch in inhibition mechanism to the loss of the thiomethyl moiety is suggested. The nonreactivation of rat brain AChE following inhibition by the (RP)-isomalathion stereoisomers is postulated to result from a mechanism involving either a beta-elimination of diethyl fumarate or displacement of the thiosuccinate moiety from the phosphate moiety. PMID- 8448347 TI - Enhancement by L-histidine of nickel(II)-induced DNA-protein cross-linking and oxidative DNA base damage in the rat kidney. AB - Formation of DNA-protein cross-links and oxidatively damaged DNA bases was investigated with the use of alkaline elution and gas chromatography/mass spectrometry techniques in the nuclei from kidneys of rats 3 and 18 h after a single iv injection of the NiII(His)2 complex (NiHis), nickel(II) acetate (NiAcet), or L-histidine (His). Administration of 20 mumol of NiHis/kg body wt caused the formation of DNA-protein cross-links and significantly increased levels of oxidatively damaged DNA bases, including 2,6-diamino-4-hydroxy-5 formamidopyrimidine (FapyGua; 3.5-fold vs the control value) 3 h postinjection and 8-oxoguanine (2.6-fold), cytosine glycol (2.5-fold), 8-oxoadenine (2-fold), and FapyGua (1.9-fold) 18 h postinjection. Injection of 20 mumol of NiAcet/kg body wt enhanced the cross-linking to a lesser extent than NiHis and did not significantly increase the amounts of modified DNA bases over the control levels. Forty micromoles of His per kilogram body wt alone caused a marked DNA-protein cross-linking effect and increased the amount of 4,6-diamino-5 formamidopyrimidine (2-fold vs the control) 3 h, but not 18 h, after treatment. The DNA base derivatives found were typical products of hydroxyl radical (.OH) attack on DNA. Formation of the cross-links may also be attributed to .OH, although other mechanisms, e.g., formation of ternary complexes of Ni(II), cannot be excluded. The present in vivo study confirms the conclusion of our former in vitro experiments that His enhances Ni(II)-mediated oxidative damage to DNA and chromatin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448348 TI - Determinants of protein modification versus heme alkylation: inactivation of cytochrome P450 1A1 by 1-ethynylpyrene and phenylacetylene. AB - Reaction of cytochrome P450 enzymes with arylacetylenes results in heme N alkylation [e.g., Komives, E. A., and Ortiz de Montellano, P. R., (1985) J. Biol. Chem. 260, 3330-3336] and/or protein modification [e.g., Gan, L.-S. L., Acebo, A. L. and Alworth, W. L. (1984) Biochemistry 23, 3827-3836]. To clarify the factors that determine whether heme or protein alkylation occurs, we have investigated the cytochrome P450 1A1-catalyzed oxidation of 1-ethynylpyrene (1-EP) and phenylacetylene (PA). Cytochrome P450 1A1 in microsomes from beta-naphthoflavone induced rats is inactivated in a time- and NADPH-dependent manner by 1-EP and PA. Parallel loss of the heme chromophore is observed with PA but not with 1-EP, although partial heme chromophore loss is observed when the purified, reconstituted enzyme is inactivated by either agent. Product analysis shows that 1-EP and PA are oxidized to, respectively, (1'-pyrenyl)-acetic and phenylacetic acids. In contrast to the inactivation of cytochrome P450 2B1 by PA, no isotope effect is observed on enzyme inactivation or metabolite formation when the acetylenic hydrogen is replaced by deuterium in either 1-EP or PA. Inactivation of cytochrome P450 1A1 by 1-EP results in covalent binding of 0.8-0.9 equiv (relative to total cytochrome P450 content) of the inhibitor to the microsomal protein. The results demonstrate that a single isozyme can be inactivated, depending on the structure of the arylacetylene, by heme or protein alkylation. Spectroscopic binding constants (Ks) show that 1-EP binds to the enzyme with > 2000 times greater affinity that PA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448349 TI - Synthesis and toxicity to mammalian cells of the carrot dihydroisocoumarins. AB - The dihydroisocoumarins (+-)-6-methoxy-8-hydroxy-3-methyl-3,4- dihydroisocoumarin (1), (+-)-6,8-dihydroxy-3-methyl-3,4-dihydroisocoumarin (2), and (+-)-6,8 dimethoxy-3-methyl-3,4-dihydroisocoumarin (3) were synthesized with high yields via metalation of o-methylbenzamides. The toxicity of these compounds and that of (-)-1 extracted from carrot cells were tested, in vitro, on Chinese hamster cells. The toxicity was determined according to the presence or absence of a hydroxyl group in the peri position of the lactonic carbonyl group and according to the stereochemistry of the dihydroisocoumarin. PMID- 8448350 TI - Caffeine-derived N-nitroso compounds. II. Synthesis and characterization of nitrosation products from caffeidine and caffeidine acid. AB - Caffeine on alkaline hydrolysis produces caffeidine [1-methyl-4-(methylamino)-5 (N-methylcarbamoyl)imidazole] and caffeidine acid [N-[4-(5-carboxy-1 methylimidazolyl)]-N,N'-dimethylurea]. We now report the synthesis and chemical characterization of mononitrosocaffeidine [1-methyl-4-(N-methyl-N-nitrosoamino)-5 (N-methylcarbamoyl)i midazole], dinitroso-caffeidine [1-methyl-4-(N-methyl-N nitrosoamino)-5-(N-methyl-N-nitrosocarb amo yl) imidazole], and mononitrosamidocaffeidine [1-methyl-4-(methylamino)-5-(N-methyl-N nitrosocarbamoyl)-Imidazole] based on spectral analysis. The characterization of nitrosated byproducts obtained during the synthesis of these compounds is also presented. Caffeidine is shown to undergo rapid nitrosation in acidic medium to form mononitrosocaffeidine (MNC), an asymmetric N-nitrosamine, and dinitrosocaffeidine (DNC), a N-nitrosamide. Although the reaction proceeds with preferential nitrosation of the amino group in caffeidine, the results also support partial involvement of a mononitrosamide intermediate in the formation of MNC and DNC through transnitrosation of the amino group. The stability data suggest that the nitroso group at the amino nitrogen in DNC influences the reactivity of amide nitroso group. The presence of a trisubstituted ureide moiety in caffeidine acid has been confirmed by NMR nuclear Overhauser effect experiments. Nitrosation of caffeidine acid under acidic conditions produced N,N' dimethylparabanic acid (DMPA, N,N'-dimethylimidazolidinetrione) as a major product with low amounts of mononitrosocaffeidine and N,N'-dimethyl-N nitrosourea, whereas nitrosation with NOBF4/pyridine in aprotic medium gave rise to an anhydride, 1,4-dimethyl-4,5-dihydro-5,7-dioxo-1H,7H-imidazo[4,5 d][1,3]oxazine. The nitrosation of methyl ester of caffeidine acid resulted in the formation of a N-nitrosourea derivative, N-[4-(5-carboxy-1-methylimidazolyl)] N'-nitroso-N,N'-dimethylurea. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448351 TI - Base-sequence dependence of covalent binding of benzo[a]pyrene diol epoxide to guanine in oligodeoxyribonucleotides. AB - The base-sequence dependence of the yield of the covalent binding reaction of (+) anti-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10 tetrahydrobenzo[a]pyrene [(+)-anti-BPDE] with the exocyclic amino group of guanine surrounded by different flanking bases X and Y in the single-stranded oligonucleotide d(CTATXGYTATC) was investigated. With an initial ratio of [(+) anti-BPDE]/[oligonucleotide strand] = 2, the percentage of modified strands varied from 20 +/- 2% when the modified dG was surrounded by pyrimidines to 5-7% when the central dG was surrounded by purines. The trans/cis ratio of (+)-anti BPDE-N2-dG adducts was in the range of 3-5. The lower reaction yields observed when the modified guanine residues in single-stranded oligonucleotides are surrounded by purines rather than by pyrimidines is tentatively attributed (1) to steric effects arising from the presence of the bulkier purines flanking the reacting dG moieties on the 5'- and 3'-sides and/or (2) to noncovalent interactions between anti-BPDE and neighboring purines which decrease the probability of optimal alignment for covalent binding between the interacting moieties in the bimolecular transition-state complex. Noncovalent intercalation of (+)-anti-BPDE prior to the covalent binding reaction is not a relevant process in the case of single-stranded oligonucleotides and is therefore not a critical requirement for obtaining high yields of covalent trans- and cis-(+)-anti-BPDE-N2 dG adducts in these oligonucleotide sequences. PMID- 8448352 TI - DNA conformation mediates aflatoxin B1-DNA binding and the formation of guanine N7 adducts by aflatoxin B1 8,9-exo-epoxide. AB - The binding of aflatoxin B1 to DNA and DNA adduction by aflatoxin B1 exo-8,9 epoxide were studied as a function of DNA conformation. Equilibrium binding of aflatoxin B1 to A-, B-, and Z-form helices was monitored by measurement of NMR linewidth for the methoxy protons of aflatoxin B1. The data revealed that as compared to B-form DNA, the association of aflatoxin with the A-form helix is significantly reduced. No binding to Z-DNA was observed. The yields obtained following reaction of the respective monomers with aflatoxin B1 exo-8,9-epoxide revealed that only dG forms an adduct. The reactivity of aflatoxin B1 exo-8,9 epoxide with single-strand DNA was determined via constant-temperature experiments in which the yield of adduct was measured for a family of oligonucleotides of increasing thermal stability. The results demonstrate that duplex structure favors adduct formation. Adduct yields were compared for A-, B-, and Z-form helices. About 12 times less adduct is produced from the A-form helix as compared to B-form, while no adduct is produced from a Z-form duplex. The results support the conclusion that reaction of aflatoxin B1 exo-8,9-epoxide with DNA proceeds via an intercalated transition-state complex only with the B-form double helix. PMID- 8448353 TI - Reactions of vitamin E and its model compound 2,2,5,7,8-pentamethylchroman-6-ol with ozone. AB - Reaction of vitamin E [(R,R,R)-alpha-tocopherol] with ozone in acetonitrile yielded alpha-tocopheryl quinone and its precursor 8a-hydroxytocopherone, which accounted for approximately 30% of the products at < 50% alpha-tocopherol oxidation. In addition, two novel products were identified as epimers of 10 acetyl-7-(4',8',12'-trimethyltridecyl)-3,4,7-trimethyl-2-oxo- 1,6-dioxaspiro[4.5] deca-3,9-diene. These spiro products were formed in equal amounts in a combined yield of approximately 33% after complete alpha-tocopherol oxidation. Ozonation of the vitamin E model compound 2,2,5,7,8-pentamethylchroman-6-ol yielded an analogous spiro product, 10-acetyl-3,4,7,7-tetramethyl-2-oxo-1,6 dioxaspiro[4.5]deca-3,9-di ene, whose structure was confirmed by X-ray crystallography. The spiro products may be formed by ozone addition to the chroman ring and subsequent rearrangement to ring-opened hydroxyacid products, which yield spiro products by ring closure due to dehydration. Novel spiro products formed by ozonation of vitamin E may be unique markers of ozone interaction with lipid structures that contain vitamin E. PMID- 8448354 TI - Selective depletion of mitochondrial glutathione concentrations by (R,S)-3 hydroxy-4-pentenoate potentiates oxidative cell death. AB - The hepatocellular glutathione content is partitioned into a cytosolic pool, which accounts for about 85% of the cellular glutathione content, and a mitochondrial pool, which accounts for about 15% of the cellular glutathione content. Previous studies indicated that the mitochondrial glutathione pool may play a critical role in cytoprotection against xenobiotic-induced cell damage. Tests of the role of mitochondrial glutathione in cytoprotection have been hampered by the lack of agents that selectively deplete the mitochondrial glutathione pool. To test the hypothesis that mitochondrial glutathione plays a critical role in protecting against cytotoxic agents, we developed a method to deplete selectively mitochondrial glutathione concentrations. (R,S)-3-Hydroxy-4 pentenoate, an analog of (R)-3-hydroxybutanoate, caused a rapid and selective depletion of mitochondrial glutathione concentrations. Incubation of (R,S)-3 hydroxy-4-pentenoate with rat liver mitochondria or with 3-hydroxybutyrate dehydrogenase in the presence of glutathione afforded a glutathione conjugate whose chromatographic properties were identical with synthetic S-(3-oxo-4 carboxybutyl)glutathione, indicating that (R,S)-3-hydroxy-4-pentenoate was oxidized to the Michael acceptor 3-oxo-4-pentenoate, which reacts with glutathione. Exposure of rat hepatocytes to (R,S)-3-hydroxy-4-pentenoate, which was not cytotoxic and did not induce mitochondrial dysfunction, potentiated the cytotoxicity of tert-butyl hydroperoxide. These results establish the critical role of mitochondrial glutathione in cytoprotection and demonstrate and (R,S)-3 hydroxy-4-pentenoate may find utility in exploring mitochondrial glutathione homeostasis. PMID- 8448355 TI - Studies on the nitroso-glyoxylate reaction. Relative hydroxamic acid production by glyoxylate, pyruvate, and formaldehyde in reactions with 4-nitrosobiphenyl. AB - The pH rate profiles for the reactions of 4-nitrosobiphenyl with three carbonyl substrates in aqueous buffers were determined by use of chromatographic and spectrophotometric methods. Glyoxylate and formaldehyde caused the conversion of 4-nitrosobiphenyl to N-(4-biphenyl)-formohydroxamic acid, while pyruvate resulted in the production of N-(4-biphenyl)acetohydroxamic acid. The dramatic effect of pH on the kinetics of these reactions provided considerable information concerning the nature of these reactions. The reactions with pyruvate and formaldehyde displayed similar pH rate profiles and were significant only at acidic pH. Glyoxylate displayed a pH rate profile that differed markedly from those of pyruvate and formaldehyde as the pH was increased beyond 2.0. The ability of glyoxylate to convert 4-nitrosobiphenyl to the hydroxamic acid increased rapidly in the pH range 2.0-4.0, above which the pH dependency was constant. This biphasic appearance of the pH rate profile was unique to glyoxylate, since the reactions of pyruvate and formaldehyde became extremely slow as solution neutrality was approached. A second substrate, 4 chloronitrosobenzene, displayed similar pH rate profiles in its reactions with these carbonyl substrates. For 4-nitrosobiphenyl, hydroxamic acid formation by glyoxylate was 10(4) times faster than that by pyruvate at neutral pH, but only about 3-fold faster at pH 1.0. The appearance of the pH rate profile for glyoxylate suggested that this alpha-oxo acid reacts with nitrosoarenes at neutrality via a pathway that is insignificant for pyruvate or formaldehyde. Thus, the nitroso-glyoxylate reaction is unique to this alpha-oxo acid under physiological pH conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448356 TI - Isolation, structural identification, and characterization of a mutagen from Fusarium moniliforme. AB - Strains of Fusarium moniliforme produce a variety of toxins, including several uncharacterized mutagens that act directly in the Ames assay using Salmonella typhimurium, strain TA 100. The Ames assay was used to monitor isolation of the direct-acting mutagens from the F. moniliforme culture extracts. Seven strains were tested, of which strains F07 and F84 contained the highest levels of direct acting mutagens. Extracts of strain F84 were fractionated on a silica gel column, eluted with methanol-chloroform (1:9). This fraction was then separated on a reverse-phase, C-18 column with 50% methanol in water as eluant and further purified by TLC. One compound was isolated and given the trivial name fusarin X (FX). Its structure was determined from its UV (lambda max 357 nm), 500-MHz NMR, and mass spectra, and those of its diacetate, to be the 1-hydroxy analog of the previously characterized fusarin C. FX was present in culture extracts of strains F07 and F84 at 83 and 8 micrograms/g, respectively, which was proportional to their relative mutagenicities. It was not detected in the other strains tested. Since exposure of FX most likely occurs in cooked corn, its thermal stability was measured; it, like FC, decomposes at 100 degrees C, especially at high pH. Again, in common with FC, it was decomposed by GSH. The possible role of these Fusarium metabolites in the etiology of human cancers has still to be resolved. PMID- 8448357 TI - Fusarin C: isolation and identification of two microsomal metabolites. AB - Fusarin C (FC), a metabolite formed by Fusarium moniliforme, is, with microsomal activation, genotoxic. Two metabolites of FC, fusarin Z (FZ) and fusarin X (FX), have been isolated from an in vitro metabolic activation system using microsomal mixtures from phenobarbital-induced rat livers and their chemical structures identified. FZ and FX are 500 and 60 times more mutagenic than FC in the Ames test, respectively. Both result from hydroxylation at the 1-position of FC. FZ is a gamma-lactone involving isomerization of the 2,3-double bond and intramolecular transesterification between the 21-methyl ester and the newly formed 1-hydroxyl group. FX, however, could not be converted to FZ by the microsomal system. PMID- 8448358 TI - Extracellular targeting of the vacuolar tobacco proteins AP24, chitinase and beta 1,3-glucanase in transgenic plants. AB - The Nicotiana tabacum ap24 gene encoding a protein with antifungal activity toward Phytophthora infestans has been characterized. Analysis of cDNA clones revealed that at least three ap24-like genes are induced in tobacco upon infection with tobacco mosaic virus. Amino acid sequencing of the purified protein showed that AP24 is synthesized as a preproprotein from which an amino terminal signal peptide and a carboxyl-terminal propeptide (CTPP) are cleaved off during post-translational processing. The functional role of the CTPP was investigated by expressing chimeric genes encoding either wild-type AP24 or a mutant protein lacking the CTPP. Plants expressing the wild-type construct resulted in proteins properly sorted to the vacuole. In contrast, the proteins produced in plants expressing the mutant construct were secreted extracellularly, indicating that the CTPP is necessary for targeting of AP24 to the vacuoles. Similar results were obtained for vacuolar chitinases and beta-1,3-glucanases of tobacco. The extracellularly targeted mutant proteins were shown to have retained their biological activity. Together, these results suggest that within all vacuolar pathogenesis-related proteins the targeting information resides in a short carboxyl-terminal propeptide which is removed during or after transport to the plant vacuole. PMID- 8448359 TI - cDNA sequence and expression of an intron-containing histone H2A gene from Norway spruce, Picea abies. AB - We have isolated a cDNA clone corresponding to a histone H2A gene from Norway spruce, Picea abies (L.) Karst. The clone was isolated on the basis of the preferential expression of the corresponding gene during germination. The identification of the clone was based on the high degree of nucleotide sequence identity (60-65%) to a range of eukaryotic histone H2A genes and the presence of a 9 amino acids long sequence identical to the conserved 'H2A box' in the deduced amino acid sequence. Like other plant histone genes, the spruce histone H2A gene encodes a polyadenylated transcript. Further, the spruce gene contains an intervening sequence of 891 bp in the coding region. The presence of introns is typical of a distinct class of replication-independent histone genes in other eukaryotes. However, the sequence of the spruce gene and its high expression in mitotically active tissues such as the apical meristem, strongly suggests that it belongs to the class of replication-dependent histone genes. This is the first documentation of an intervening sequence in this class of histone genes and the finding implies that introns were present in the ancestral histone H2A gene before the divergence of the two classes of histone genes. PMID- 8448360 TI - Phylogenetic distribution and genetic mapping of a (GGC)n microsatellite from rice (Oryza sativa L.). AB - DNA microsatellites are ubiquitously present in eukaryotic genomes and represent a vast source of highly informative markers. We describe in this article a (GGC)n microsatellite which is widely distributed in eukaryotic genomes. Using polymerase chain reaction (PCR) techniques and DNA sequencing, we demonstrated for the first time in plant species that a (GGC)n microsatellite locus is moderately polymorphic. Six alleles are present at this locus in rice and length polymorphisms are caused by variation in the number of tandem GGC repeats. By scoring a backcross mapping population, we were able to demonstrate that this locus is stably inherited and does not link to any known RFLP markers on the rice RFLP map. Our results suggest that DNA microsatellites should be useful in plants for construction of genetic linkage maps, extension of the existing genetic linkage maps, linkage analysis of disease and pest resistance genes, and the study of population genetics. PMID- 8448361 TI - The salicylic acid-inducible alternative oxidase gene aox1 and genes encoding pathogenesis-related proteins share regions of sequence similarity in their promoters. AB - We have isolated and characterized a genomic clone, lambda AOSG11, corresponding to aox1, which encodes the 42 kDa alternative oxidase precursor protein of Sauromatum guttatum Schott. The sequence of lambda AOSG11 revealed that aox1 consists of four exons separated by three short introns. Exon three contains the region of aox1 that (1) is highly conserved in the corresponding genes of potato, rice, and yeast, and (2) encodes a region of the deduced protein that is predicted to form two transmembrane alpha-helices. Southern blot analysis of restriction endonuclease-digested genomic DNA, indicated that aox1 is a single, nuclear-encoded gene in S. guttatum. We have determined the transcriptional start site of aox1 using nuclease protection and primer extension experiments. Comparison of the putative promoter region of aox1 to promoters of PR1a and GRP8 revealed some sequence similarity. PMID- 8448362 TI - A functional map of the fruit-specific promoter of the tomato 2A11 gene. AB - The 5' region of the fruit-specific tomato gene, 2A11, contains both positive and negative regulatory elements. We divided the 5' promoter region of the 2A11 gene into small fragments, ranging in size from 211 to 634 bp and used these short DNA fragments in in vitro protein-binding studies. These studies revealed the presence of at least four fruit-specific and one leaf- and fruit-active protein binding domains. These promoter fragments, as well as other overlapping fragments, were tested for their ability to enhance expression from a truncated heterologous promoter in transgenic plants. This analysis showed the presence of four fruit-specific and three general or leaf-active positive regulatory elements. Comparison of the results obtained with these two approaches allowed us to draw a functional map of the 2A11 promoter. PMID- 8448363 TI - Differential expression of two related, low-temperature-induced genes in Arabidopsis thaliana (L.) Heynh. AB - Plant cold acclimation is correlated to expression of low-temperature-induced (lti) genes. By using a previously characterized lti cDNA clone as a probe we isolated a genomic fragment that carried two closely located lti genes of Arabidopsis thaliana. The genes were structurally related with the coding regions interrupted by three similarly located short introns and were transcribed in the same direction. The nucleotide sequences of the two genes, lti78 and lti65, predict novel hydrophilic polypeptides with molecular weights of 77,856 and 64,510, respectively, lti78 corresponding to the cDNA probe. Of the 710 amino acids of LTI78 and 600 amino acids of LTI65, 346 amino acids were identical between the polypeptides, which suggests that the genes may have a common origin. Both lti78 and lti65 were induced by low temperature, exogenous abscisic acid (ABA) and drought, but the responsiveness of the genes to these stimuli was markedly different. Both the levels and the temporal pattern of expression differed between the genes. Expression of lti78 was mainly responsive to low temperature, that of lti65 to drought and ABA. In contrast to the induction of lti78, which follows separate signal pathways during low-temperature, ABA and drought treatment, the drought induction of lti65 is ABA-dependent and the low temperature induction appears to be coupled to the ABA biosynthetic pathway. This differential expression of two related genes may indicate that they have somewhat different roles in the stress response. PMID- 8448364 TI - Expression of a cysteine proteinase inhibitor (oryzacystatin-I) in transgenic tobacco plants. AB - Expression of cysteine proteinase inhibitors (cystatins) in tobacco or other plants has the potential for improving resistance against pathogens and insects that possess cysteine proteinases. A chimeric gene containing a cDNA clone of rice cystatin (oryzacystatin-I; OC-I), the cauliflower mosaic virus 35S promoter, and the nopaline synthase 3' region was introduced into tobacco plants by Agrobacterium tumefaciens. The presence of the chimeric gene in transgenic plants was detected by a polymerase chain reaction-amplified assay, and transcriptional activity was shown by RNA blot analysis. Heated extracts from transgenic tobacco plants, as well as from progeny which were obtained by selfing a primary transformant, contained protein bands that corresponded in molecular mass to OC-I and reacted with antibodies raised against rOC, a recombinant OC-I protein produced by Escherichia coli. Similar bands were absent in extracts from untransformed control plants. OC-I levels reached 0.5% and 0.6% of the total soluble proteins in leaves and roots, respectively, of some progeny. On a fresh weight basis, the OC-I content was higher in leaves (50 micrograms/g) than in roots (30 micrograms/g). OC-I was partially purified from protein extracts of rice seeds and from transgenic tobacco leaves by affinity to anti-rOC antibodies. OC-I from both sources was active against papain. PMID- 8448365 TI - Resistance to cymbidium ringspot tombusvirus infection in transgenic Nicotiana benthamiana plants expressing the virus coat protein gene. AB - Transgenic Nicotiana benthamiana plants expressing the coat protein gene of cymbidium ringspot virus (CyRSV) were tested for resistance against infection with CyRSV. Transgenic plants showed resistance to infection only when the purified virions concentration in the inoculum was as low as 0.05 micrograms/ml. No protection was observed in transgenic plants inoculated with virion concentrations of 0.5 and 5.0 micrograms/ml or when the inoculum was in vitro synthesized genomic RNA. PMID- 8448366 TI - Circadian expression and induction by wounding of tobacco genes for cysteine proteinase. AB - Two sets of clones were isolated from a tobacco cDNA library, utilizing as a probe a PCR fragment obtained from tomato cDNA using a degenerate primer based on the sequence of tomato systemin. Contrary to expectation, the clones did not correspond to tobacco homologues of tomato pro-systemin. However, the cDNAs encoded two highly similar proteins with extensive structural homology to cysteine proteinases from a wide range of plant and animal species. Northern blot analyses showed that in unstressed tobacco leaf the genes for the putative proteinases are expressed according to a circadian rhythm. Furthermore, incision wounding enhances the expression approximately six-fold. Other forms of stress, such as infection with tobacco mosaic virus, treatment with ethephon or UV light do not result in induced expression of the tobacco cysteine proteinase genes. PMID- 8448367 TI - Two cDNAs from Arabidopsis thaliana encode putative RNA binding proteins containing glycine-rich domains. AB - Two related DNA sequences encoding small (-17kDa) glycine-rich proteins (GRPs) have been isolated from an Arabidopsis thaliana cDNA library. AtGRP7 and AtGRP8 encode proteins with a bipartite structure consisting of an amino-terminal putative RNA-binding domain and a carboxyl-terminal domain composed of stretches of glycines and serines with interspersed hydrophilic residues. These cDNAs exhibit structural similarity to a class of stress-induced transcripts found in other plant species. The proteins encoded by AtGRP7 and AtGRP8 may be members of a family of proteins which serve a vital role in RNA transcription or processing during stress. PMID- 8448368 TI - cDNA nucleotide sequence and expression of a maize cytoplasmic ribosomal protein S13 gene. AB - The complete amino acid sequence of a cytoplasmic ribosomal protein S13 of maize was deduced from the cDNA isolated from a maize cDNA library. The encoded protein is 151 amino acids long and shows a homology of 73% with the corresponding protein S13 of rat. Southern blots analysis shows that the maize protein S13 is encoded by a small multigene family conserved in plant species closely related to maize. The S13 RNAs accumulate preferentially in proliferating tissues and cells and their transcription occurs in parallel to the DNA synthesis. PMID- 8448369 TI - Transgenic tobacco plants regenerated from leaf disks can be periclinal chimeras. AB - Amongst rolC transgenic tobacco plants regenerated from leaf disks 6.5% are periclinal chimeras, i.e. plants with genetically different cell populations in different cell layers. The expression of the rolC gene of Agrobacterium rhizogenes causes a reduction in pigment content in leaves. The chimeric composition of the regenerated plants becomes thus apparent as light green leaf tissue in the transgenic region, tissue flanked by dark green wild-type sectors. Southern and northern blot analysis confirmed the chimeric nature of such plants. Investigation of selfed progeny of chimeric plants on selective media indicates that layer invasion in reproductive tissues can occur in tobacco early during the formation of the flower buds. The results show (1) that tobacco plants regenerated from leaf disks and grown on selective media have not necessarily the same clonal origin and (2) that they can give rise to non-transgenic offspring. The chimeric plants provide insight on the effect of rolC gene expression on microsporogenesis. PMID- 8448370 TI - Molecular cloning and characterization of a legumin-like storage protein cDNA of Douglas fir seeds. AB - A cDNA library was made from poly(A)+ RNA isolated from developing Douglas fir (Pseudotsuga menziesii) embryo and megagametophytic tissue, and the cDNA clones were identified by immunoscreening with polyclonal antiserum against the crystalloid storage protein complex of Douglas fir. The nucleotide sequence of the longest cDNA insert (DF1) was analysed. The amino acid sequence derived from the DNA sequence verified its identity as a legumin-like storage protein (pseudotsugin) and confirmed that the protein is synthesized as a precursor similar to the 11-12S storage globulins. The transcripts corresponding to cDNA insert DF1 were abundant in the early- to mid-stages of embryogenesis in the diploid embryonic axes as well as in the haploid megagametophytic tissue. The deduced amino acid sequence of pseudotsugin consists of a 29 amino acid N terminal signal peptide preceding the acidic polypeptide region (286 amino acids) and the subsequent basic polypeptide region (212 amino acids). The site for post transcriptional cleavage of the precursor polypeptide to make the A and B polypeptides is localized between asparagine -315 and glycine -316 and is highly conserved between angiosperms and gymnosperms. The deduced amino acid sequence for the DF1 cDNA clone reveals that pseudotsugin is rich in arginine, glutamic acid and serine and is low in cysteine, methionine and lysine. Comparison of the deduced amino acid sequence of Douglas fir pseudotsugin shows between 29-38.5% identity with angiosperm species, 63% identity with interior spruce, and 60% identity with eastern white pine. PMID- 8448371 TI - Nucleotide sequence and characterization of a cDNA encoding the acetohydroxy acid isomeroreductase from Arabidopsis thaliana. AB - The primary structure of acetohydroxy acid isomeroreductase from Arabidopsis thaliana was deduced from two overlapping cDNA. The full-length cDNA sequence predicts an amino acid sequence for the protein precursor of 591 residues including a putative transit peptide of 67 amino acids. Comparison of the A. thaliana and spinach acetohydroxy acid isomeroreductases reveals that the sequences are conserved in the mature protein regions, but divergent in the transit peptides and around their putative processing site. PMID- 8448372 TI - Supported PCR: an efficient procedure to amplify sequences flanking a known DNA segment. AB - We describe a novel modification of the polymerase chain reaction for efficient in vitro amplification of genomic DNA sequences flanking short stretches of known sequence. The technique utilizes a target enrichment step, based on the selective isolation of biotinylated fragments from the bulk of genomic DNA on streptavidin containing support. Subsequently, following ligation with a second universal linker primer, the selected fragments can be amplified to amounts suitable for further molecular studies. The procedure has been applied to recover T-DNA flanking sequences in transgenic tomato plants which could subsequently be used to assign the positions of T-DNA to the molecular map of tomato. The method called supported PCR (sPCR) is a simple and efficient alternative to techniques used in the isolation of specific sequences flanking a known DNA segment. PMID- 8448373 TI - Expression of an ABA-responsive osmotin-like gene during the induction of freezing tolerance in Solanum commersonii. AB - We have isolated a cDNA (pA13) of an ABA-responsive gene from suspension cultures of Solanum cultures of Solanum commersonii. The deduced amino acid sequence of pA13 cDNA revealed 89 and 91% identity with tobacco osmotin and tomato NP24 protein, respectively. The accumulation of the transcript corresponding to pA13 cDNA was regulated by ABA, cold temperature, and low water potential treatments. Cold-induced accumulation of the pA13 transcript was partially suppressed by fluridone, an ABA synthesis inhibitor, and the suppression was restored by exogenous ABA application. The transcript corresponding to pA13 also accumulated in an organ-specific manner in response to ABA or cold treatment. PMID- 8448374 TI - Amplification of N-myc as a prognostic marker for patients with neuroblastoma. AB - N-myc is amplified between 5 and several hundred-fold frequently in neuroblastomas and, at lower frequency, in other human cancers with neuronal qualities, including retinoblastomas, gliomas, astrocytomas and small cell lung cancers. In neuroblastomas N-myc amplification is significantly correlated with poor prognosis; for other types of tumors such a correlation is difficult to make, due to low incidence of amplification. Amplification is associated with elevated expression, both of mRNA and protein. N-myc encodes two polypeptides of relative masses of 62 and 64 kDa, which are phosphorylated, at least in vitro, by casein kinase II and that are localized in the nucleus. There they can associate in vivo with another protein, Max, through a C-terminal dimerization motif, the leucine zipper. An N-terminal portion of N-myc, referred to as 'Myc-boxes', can substitute for the transcription-activating function of the yeast transcription factor Gal 4, thus raising the possibility that N-myc itself may act as a transcription factor, either alone or in association with other factors. PMID- 8448375 TI - Amplified genes in human gliomas. AB - The most common types of brain tumors in adults are collectively known as gliomas. The most common glioma is the most malignant, the glioblastoma. Double minute chromosomes, known to represent amplified genes, are found in 50% of glioblastomas. Four genes have been identified as being amplified in more than single cases of glioblastomas; MYCN, GLI, PDGFRA and EGFR. The first three have been reported in a few per cent of malignant gliomas, and EGFR in around 40% of glioblastomas. The latter two genes code for growth factor receptors. On amplification, the genes for these receptors frequently become rearranged, resulting in changes in the regions of their transcripts that code for the extra cellular domains of these proteins. Such aberrant proteins may provide us with cell-surface, tumor-specific, epitopes. These findings provide simple examples of the impact the use of modern molecular biological techniques will have for our understanding and treatment of tumors in the future. PMID- 8448376 TI - Role of myc amplification and overexpression in cell growth, differentiation and death. AB - Genes of the myc family are apparently the most intensively studied of all nuclear oncogenes. This is because their expression is deregulated in many types of human neoplasia due to chromosomal translocation or gene amplification, and because their exact roles in the regulation of cell proliferation have remained poorly known. However, the recent characterization of several domains in Myc proteins that enable sequence-specific regulation of other growth-related genes, and the identification of proteins interacting with Myc proteins have provided insight into the function(s) of Myc proteins in both normal and neoplastic cells. While the natural target genes for Myc remain to be identified, it has become evident that myc overexpression not only promotes cell proliferation, but also increases the rate of programmed cell death. PMID- 8448377 TI - Comparative genomic hybridization: a rapid new method for detecting and mapping DNA amplification in tumors. AB - Recent evidence indicates that many more genes than the currently known oncogenes may undergo amplification in tumors. We have developed a new technique, Comparative Genomic Hybridization (CGH), which allows rapid detection of DNA amplification anywhere in the tumor genome and maps the amplified sequences on normal chromosomes. CGH is based on a competitive in situ hybridization of differentially labeled tumor DNA and normal DNA to a normal human metaphase spread. Regions of gain of DNA sequences are seen as an increased color ratio of two fluorochromes used to detect the labeled DNAs. Over 20 different regions of amplification have been identified using CGH. PMID- 8448378 TI - Differential polymerase chain reaction in the analysis of gene dosage. AB - Abnormalities of gene dosage are important in human disease. We have developed the differential polymerase chain reaction (PCR) to detect gene amplification and deletion in small amounts of tissues whose DNA may be degraded. The current utility of differential PCR required optimization of DNA isolation procedures, of primer selection approaches, and of PCR conditions. From this experience, we have formulated a theoretical framework for the technique, and describe appropriate applications and potential improvements based on emerging PCR technologies. Special emphasis is placed on the analysis of formalin fixed and paraffin embedded, archived specimens. PMID- 8448379 TI - Why should glycobiologists be interested in mass spectrometry? PMID- 8448380 TI - Processing inhibition of N-linked sugar chains associated with induction of Fc receptor-mediated phagocytosis in the mouse monocytoid cells. AB - The concanavalin A staining of cellular glycoproteins and the direct analysis of their sugar chains released by hydrazinolysis revealed that the processing of N linked sugar chains of some glycoproteins is suppressed by exposure of mouse monocytoid cells P388D1 to dimethyl sulphoxide, which can induce Fc receptor mediated phagocytosis. To elucidate the significance of altered glycosylation in inducing phagocytosis, the effects of exposure of the cells to processing inhibitors (swainsonine and castanospermine) were examined and it was found that the cells are induced to acquire an ability to ingest IgG-coated sheep red blood cells, depending on the dose of the inhibitors and incubation time. Analysis of the N-linked sugar chains liberated from cellular glycoproteins by hydrazinolysis confirmed that the processing of the sugar chains is suppressed by the two inhibitors as expected. Since no significant alteration was induced in protein synthesis and DNA synthesis after exposure to the inhibitors, it is suggested that the altered glycosylation of cellular glycoproteins may have some direct role in the induction of Fc receptor-mediated phagocytosis. The inhibitors did not affect the binding of the IgG-coated red blood cells to Fc receptors on the cells, non-specific phagocytosis of latex beads, and the contents of lysosomal enzymes, beta-glucuronidase and acid phosphatase. These results suggest that the glycosylation status of cellular glycoproteins influences some specific processes involved in the ingestion of the ligands bound to Fc receptors. PMID- 8448381 TI - A conserved disulphide bond in sialyltransferases. PMID- 8448382 TI - Evidence for a lactose-mediated association between two nuclear carbohydrate binding proteins. AB - Nuclear proteins were extracted in 2 M NaCl from membrane-depleted nuclei isolated from HL60 cells. Extracted proteins were submitted to affinity chromatography columns containing immobilized glucose, galactose or lactose. The polypeptides present in the different eluted fractions were resolved by SDS-PAGE and were either silver stained or analysed by immunoblotting with monoclonal or polyclonal antibodies, respectively, raised against the glucose-binding protein CBP67 and the galactose-binding proteins CBP35 and L14. The results presented here show that HL60 cell nuclei contain CBP35 and a glucose-binding lectin of 70 kDa (CBP70). These data account for the previously reported binding of neoglycoproteins containing glucosyl and galactosyl residues to HL60 cell nuclei. Furthermore, the present study provides the new information that CBP35 can associate with CBP70 by interactions dependent on the binding of CBP35 to lactose, and the results of some affinity chromatography experiments strongly suggest that CBP35 and CBP70 associate by protein-protein interactions. The potential function of this lactose-mediated interaction is discussed with respect to data recently reported by others showing that CBP35 is involved in in vitro mRNA splicing and that lactose inhibits the processing of the pre-RNA substrate. PMID- 8448383 TI - Are heparan sulphate (HS) sulphotransferases implicated in the pathogenesis of Alzheimer's disease? PMID- 8448384 TI - Monoclonal antibody specific to alpha-2-->3-linked deaminated neuraminyl beta galactosyl sequence. AB - Fusion of spleen cells from a BALB/c mouse immunized with KDN alpha 2-->3Gal beta 1-->4Glc beta 1-->1Cer ((KDN)GM3) with P3-X63 Ag8.U1 (P3U1) mouse myeloma cells yielded a hybrid cell line that produced monoclonal antibody that bound to (KDN)GM3, but not to Neu5Ac alpha 2-->3Gal beta 1-->4Glc-beta 1-->1Cer ((Neu5Ac)GM3). The specificity of the monoclonal antibody was determined chiefly by the enzyme-linked immunosorbent assay procedure. This antibody was found to react most strongly with (KDN)GM3 and less strongly with a glycoprotein containing a number of KDN alpha 2-->3Gal beta 1-->3-GalNAc alpha 1-->3[8KDN alpha 2-->)n-->6]GalNAc alpha 1-->chains (< n > av = approximately 3). The results indicated that the monoclonal antibody (designated mAb.kdn3G) specifically and effectively recognized a disaccharide structure, KDN alpha 2- >3Gal beta 1-->, and specifically discriminated (KDN)GM3 from (Neu5Ac)GM3. The mAb.kdn3G was used to localize (KDN)GM3 in rainbow trout sperm by the indirect immunofluorescence procedure and the antigen was shown to be mostly, if not completely, associated with the external surface of the entire plasma membrane of rainbow trout sperm. The potential utility of mAb.kdn3G is addressed in searching for KDN-glycoconjugates which contain glycan units having the KDN alpha 2-->3Gal beta 1-->epitope structure. PMID- 8448385 TI - Ribonuclease activity of sialic acid-binding lectin from Rana catesbeiana eggs. AB - Sialic acid-binding lectin (SBL) isolated from Rana catesbeiana eggs is a basic protein which agglutinates a large variety of tumour cells and has an amino acid sequence homologous to that of human angiogenin and pancreatic ribonuclease (RNase). Although SBL and angiogenin lack the Cys-65-Cys-72 disulphide bond of pancreatic RNase, the locations of the other three disulphide bonds are similar among the three molecules. SBL was found to exhibit RNase activity, as well as catalytic properties resembling those of bovine RNase A in some respects. For example, SBL hydrolyses poly(uridylic acid) and poly(cytidylic acid) as substrates, and prefers the former. RNase A and angiogenin are strongly inhibited by human placental RNase inhibitor, whereas the RNase activity and tumour cell agglutination activity of SBL are not affected by this inhibitor. PMID- 8448386 TI - Variable subcellular localization of glycosphingolipids. AB - Although most glycosphingolipids (GSLs) are thought to be located in the outer leaflet of the plasma membrane, recent evidence indicates that GSLs are also associated with intracellular organelles. We now report that the subcellular localization of GSLs varies depending on the GSL structure and cell type. GSL localization was determined by indirect immunofluorescence microscopy of fixed permeabilized cells. A single GSL exhibited variable subcellular localization in different cells. For example, antibody to GalCer is localized primarily to the plasma membrane of HaCaT II-3 keratinocytes, but to intracellular organelles in other epithelial cells. GalCer is localized to small vesicles and tubulovesicular structures in MDCK cells, and to the surface of phase-dense lipid droplets in HepG2 hepatoma cells. Furthermore, within a single cell type, individual GSLs were found to exhibit different patterns of subcellular localization. In HepG2 cells, LacCer was associated with small vesicles, which differed from the phase dense vesicles stained by anti-GalCer, and Gb4Cer was associated with the intermediate filaments of the cytoskeleton. Both anti-GalCer and monoclonal antibody A2B5, which binds polysialogangliosides, localized to mitochondria. The distinct subcellular localization patterns of GSLs raise interesting questions about their functions in different organelles. Together with published data on the enrichment of GSLs in specific organelles and in apical plasma membrane, these findings indicate the existence of specific sorting mechanisms that regulate the intracellular transport and localization of GSLs. PMID- 8448387 TI - Cell surface glycoconjugates as possible target structures for human natural killer cells: evidence against the involvement of glycolipids and N-linked carbohydrate chains. AB - Natural killer (NK) cells can spontaneously kill various malignant cells, but the susceptibility towards NK cells differs greatly among different types of tumour cells. The molecules, which are recognized by NK cells, have not yet been identified, but there is ample evidence that target cell surface glycoconjugates are involved in the interaction with NK cells. In this report, we show that the recognition of K562 target cells by human NK cells depends on the presence of protein-bound determinants, implying that glycolipids are not the primary target structures on K562 cells. The NK susceptibility of K562 cells was not altered by enzymic removal of various cell surface carbohydrates or oligosaccharides, mostly related to N-linked carbohydrate chains. Treatment of K562 cells with 1 deoxynojirimycin and 1-deoxymannojirimycin, inhibitors of N-glycan processing, resulted in drastic alterations in the carbohydrate phenotype of the cell surface, as could be shown by flow cytometric analysis of the lectin-binding properties of the cells. Despite these clear changes in N-glycosylation, the NK susceptibility of K562 cells remained unaffected. Summarizing, the results described in this report show that potential target structures for NK cells are protein bound, but the involvement of a specific (N-linked) carbohydrate determinant in the interaction between NK cells and target cells could not be established. PMID- 8448388 TI - Human Lewis alpha 1-->3/4fucosyltransferase: specificity of fucose transfer to GlcNAc beta 1-->3Gal beta 1-->4Glc beta 1-->1Cer (LcOse3Cer). AB - Biosynthesis of the Lex series of carbohydrate antigens proceeds by fucose transfer in alpha 1-->3-linkage to the pen-ultimate GlcNAc residue of a neolacto series oligosaccharide acceptor, a reaction catalysed by multiple enzymes expressed in human tissues. Particularly broad acceptor specificity, including the ability to catalyse fucose transfer to both lacto- and neolacto-series acceptors as well as the precursor Lc3 structure (where Lc3, lactotriaosylceramide, is GlcNAc beta 1-->3Gal beta 1-->4Glc beta 1-->1Cer), exists for one human fucosyltransferase form, the Lewis alpha 1- >3/4fucosyltransferase (FucT-III). To determine if fucose transfer to Lc3 may represent an alternate early step in Le(x) or Le(a) antigen biosynthesis with this enzyme, the chemical structure of the fucosylated Lc3 reaction product formed by the Lewis alpha 1-->3/4fucosyltransferase from Colo 205 cells has been defined. Transfer of [14C]fucose to Lc3 yielded a labelled product migrating as a tetrasaccharide on thin layer chromatography plates. This product remained an acceptor for both beta 1-->3- and beta 1-->4-galactosyl transfer on the terminal GlcNAc residue. The product was degraded to a fucosylated trisaccharide derivative by bovine kidney beta-N-acetylglucosaminidase. Fast atom bombardment mass spectrometry and methylation analysis confirmed that the product was composed exclusively of the following structure containing a fucose linked to the 3-position of the internal Glc residue: [formula; see text] Such a structure does not represent an intermediate in Le(x) or Le(a) antigen biosynthesis. Thus, the evidence suggests that Le(x) or Le(a) antigen synthesis results exclusively from fucosylation of complete core chains. PMID- 8448389 TI - Selective impairment of the synthesis of basic fibroblast growth factor binding domains of heparan sulphate in a COS cell mutant defective in N sulphotransferase. AB - N-Sulphation is a key step in the overall sulphation of heparan sulphate. We have isolated a COS cell-derived mutant, CM-15, that is impaired in its ability to bind to basic fibroblast growth factor (bFGF) and has a 2- to 3-fold reduction in N-sulphotransferase activity [Ishihara et al., (1992a) Anal. Biochem., 206, 400 407]. We now provide structural evidence that CM-15 is selectively impaired in the synthesis of highly sulphated regions or 'blocks' that display high-affinity binding to bFGF; these are completely N-sulphated blocks of decasaccharide or greater length that are enriched in O-sulphate groups. The synthesis of sulphated blocks that did not show high affinity to the growth factor was relatively unimpaired in the mutant cells; this included fully N-sulphated octamer (or smaller) blocks and, unexpectedly, decasaccharide or larger blocks that were poorly O-sulphated. In the latter fraction, the failure to form high-affinity binding regions was the result of a failure to stimulate O-sulphation rather than N-sulphation in CM-15 cells. In agreement with other studies, disaccharide analysis of the wild-type-derived sulphated blocks suggested that 2-O-sulphation of iduronate residues in the polymer was a necessary element to produce a high affinity binding sequence once N-sulphation was completed in the decasaccharide or larger fraction. These results suggest that a selective reduction in both N- and O-sulphation in the larger blocks produced by CM-15 cells is a consequence of the reduction of N-sulphotransferase activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448390 TI - Type II integral membrane proteins with characteristics of C-type animal lectins expressed by natural killer (NK) cells. PMID- 8448391 TI - The Williams S. Moore Award. PMID- 8448392 TI - Cirrhosis: multiobserver analysis of hepatic MR imaging findings in a heterogeneous population. AB - To investigate the magnetic resonance (MR) imaging findings of hepatic cirrhosis and the potential of MR imaging in differentiating cirrhosis from other hepatic abnormalities, three observers with different levels of expertise in MR imaging (specialist, experienced radiologist, and novice with special training) reviewed hepatic MR imaging examinations of 52 patients with biopsy-proved presence (n = 29) or absence (n = 23) of cirrhosis. All examinations included motion compensated T1-weighted, T2-weighted, and flow-sensitive gradient-echo images. For all three observers, linear signal irregularity was more accurate than other findings. For the final diagnosis of cirrhosis, the specialist was most sensitive (76% at high threshold, 97% at low threshold), followed by the novice with special training (31% and 79%, respectively). Specificity was 100% for all observers at high threshold and 78%, 96%, and 87% for expert, experienced, and trained novice observers, respectively, at low threshold. Sensitivity did not vary regardless of severity of fibrosis, as determined independently by a hepatopathologist. MR imaging has the potential of offering a comprehensive noninvasive evaluation of patients with suspected cirrhosis, but considerable expertise is required at present. PMID- 8448393 TI - T2-weighted MR imaging of focal hepatic lesions: comparison of various RARE and fat-suppressed spin-echo sequences. AB - The authors prospectively compared four T2-weighted magnetic resonance (MR) sequences, including high-resolution 512 x 512 (matrix size) RARE (rapid acquisition with relaxation enhancement), 256 x 256 RARE, 128 x 256 breath-hold RARE, and 192 x 256 fat-suppressed spin-echo (T2FS) sequences, in the evaluation of 16 patients with focal hepatic masses. MR images were evaluated by quantitative lesion-liver signal difference-to-noise ratios (SDNRs) and subjective evaluation of image artifact and image quality. No significant differences were observed between RARE sequences in SDNR values. The T2FS sequence had a significantly higher SDNR than the 512 x 512 RARE sequence (24.6 +/- 15.0 vs 14.5 +/- 9.7) (P = .008). Image quality was rated highest for the 512 x 512 RARE and T2FS sequences (P = .006). The inherent advantage of high spatial resolution suggests that the 512 x 512 RARE sequence may be of value in detecting hepatic lesions. PMID- 8448394 TI - Preoperative local staging of rectal carcinoma with MR imaging and a rectal balloon. AB - Magnetic resonance (MR) imaging for the preoperative assessment of rectal carcinoma was evaluated. Thirty-three patients underwent MR imaging with a 1.5-T unit. On the basis of results of barium enema studies and/or digital examination, a balloon catheter was inserted to the level of the lesion before MR imaging. Both T1- and T2-weighted axial spin-echo images were obtained in all patients. With the balloon catheter, the three layers of the normal bowel wall could be seen on T2-weighted images. Muscular invasion was detected with a sensitivity of 90%, a specificity of 84%, a positive predictive value of 90%, a negative predictive value of 84%, and an overall accuracy of 88%. False-positive results were related to chemical shift artifact and intramural lymph node metastases. Perirectal fat invasion was detected with a sensitivity of 64%, a specificity of 89%, a positive predictive value of 82%, a negative predictive value of 77%, and an overall accuracy of 79%. One of the false-positive results was related to intramural lymph node metastases and the other to perirectal vessels. Evaluation of adjacent organ invasion was accurate in all patients. Lymph node metastasis was correctly detected in six of nine patients. Absence of lymph node metastasis was correctly predicted in 23 of 24 patients. Thus, MR imaging with a balloon catheter was useful for detection of tumor invasion into muscularis propria and adjacent organs; however, its demonstration of perirectal fat and lymph node involvement was less accurate. PMID- 8448395 TI - Evaluation of adrenal masses with gadolinium enhancement and fat-suppressed MR imaging. AB - A study was undertaken to determine the ability to characterize benign and malignant masses with unenhanced and contrast material-enhanced fast low-angle shot and fat-suppressed spin-echo magnetic resonance (MR) imaging. Thirty patients with adrenal masses detected at computed tomography (CT) underwent MR imaging within 14 days after CT. CT and MR images were interpreted in a prospective, blinded fashion. Sixteen patients had 20 benign adrenal masses, and 14 patients had 18 malignant masses. Quantitative measurements included percentage of contrast enhancement on immediate postcontrast dynamic images and periphery--center signal-to-noise ratio (S/N) on gadolinium-enhanced fat suppressed images. Qualitative evaluation included determination of the regularity of lesion margins, homogeneity of signal intensity, and local extension. MR imaging depicted all adrenal masses discovered at CT examinations. Lesions ranged in diameter from 1 to 15 (mean, 4.4) cm. No significant difference was observed in percentage of contrast enhancement between benign (90.5% +/- 59.0 [standard deviation]) and malignant (110.5% +/- 116.4) masses. A difference was observed between periphery--center S/N for benign (-.05 +/- 1.5) and malignant (7.7 +/- 9.8) masses; overlap between the two, however, occurred. Qualitative evaluation allowed correct characterization of 32 of 38 masses, comparing favorably with CT, which allowed characterization of 30 lesions. PMID- 8448396 TI - Efficacy and safety of gadopentetate dimeglumine in the evaluation of patients with a suspected tumor of the extracranial head and neck. AB - The clinical efficacy and safety of gadopentetate dimeglumine as a paramagnetic contrast agent for magnetic resonance (MR) imaging of the extracranial head and neck was evaluated in a multicenter trial involving 60 patients. Patients with signs and/or symptoms of a tumor in the nasopharynx, oropharynx, hypopharynx, larynx, or neck were studied. T1-weighted images were obtained before and after injection of gadopentetate dimeglumine, 0.1 mmol/kg, at a rate of 10 mL/min. No lesions were seen on the pre- or postinjection images of five of the 60 patients. Postinjection lesion enhancement was present in 53 of the remaining 55 (96%) patients. The absence of postinjection lesion enhancement in one of the two remaining patients was useful information. Postinjection impressions differed from preinjection diagnosis in 22 of 60 (37%) patients. Additional information was obtained from postinjection relative to preinjection images in 38 of 60 (63%) patients. Four adverse experiences were reported in three of 60 (5%) patients. Two mild (chest wall pain and headache) and one moderate (nausea) adverse experiences were considered by the authors to be unrelated to the studied drug. One severe adverse experience was reported. This patient had a seizure, considered by the investigator to be remotely related to the study drug and attributed to the abrupt withdrawal of anticonvulsant medications. The data indicate that gadopentetate dimeglumine is safe and efficacious in the evaluation of patients with extracranial head and neck lesions. PMID- 8448397 TI - Boronated metalloporphyrins: a novel approach to the diagnosis and treatment of cancer using contrast-enhanced MR imaging and neutron capture therapy. AB - Porphyrins are a unique class of metal chelating agents that have shown specific affinity for neoplasms. The water-soluble free-base derivative, tetrakiscarborane carboxylate ester of 2,4-(alpha,beta-dihydroxyethyl) deuteroporphyrin IX (BOPP), an agent designed for neutron capture therapy, has previously demonstrated selective localization and retention in a C6 murine glioma. In the present work, the authors demonstrate that the manganese chelate of BOPP also selectively localizes in a rat 9L gliosarcoma and preferentially enhances the tumor-normal brain contrast of T1-weighted images for at least 92 hours. The data indicate a maximal enhancement of contrast between tumor and normal brain at 24 hours after injection, compared with 5 minutes for manganese (III) tetraphenylporphine sulfonate (TPPS4). The results also indicate that Mn-BOPP may have a slower uptake in the 9L glioma than Mn-TPPS4 but a longer retention in the tumor. Mn BOPP is unique in that it represents, to the authors' knowledge, the first example of a single agent that can enhance contrast between tumor and normal tissue and be potentially effective as an agent for boron neutron capture therapy. PMID- 8448398 TI - Three-dimensional MR reconstruction images of skull base tumors. AB - Forty-eight patients with skull base tumors were evaluated prospectively with T1 weighted spin-echo two-dimensional (2D) magnetic resonance (MR) sequences, a three-dimensional (3D) MR TurboFLASH (fast low-angle shot) sequence, and a 3D reconstruction window technique. All patients underwent surgery with histopathologic correlation, and the three MR imaging techniques were compared to assess representation of tumor margins and the topographic relationship of tumor to surrounding tissue and adjacent vasculature. The best results were obtained with standard 2D spin-echo sequences after administration of the paramagnetic contrast agent gadopentetate dimeglumine. The 2D MR sequences gave the highest contrast-to-noise ratios, with decreasing values for 3D sequences and 3D reconstructions, respectively. Nevertheless, 3D MR imaging, by virtue of its good representation of adjacent structures, aided surgeons in planning surgical intervention. This study presents the technical features of 3D imaging of the skull base, the choices involved in its implementation, and its potential clinical applications. PMID- 8448399 TI - Three-dimensional time-of-flight MR angiography with a specialized gradient head coil. AB - A gradient head coil has been developed, incorporating two independent gradients within the conventional body coil of the magnetic resonance (MR) system, with reduced rise times (200 microseconds) and maximum amplitudes of 37 and 18 mT/m in the z and y directions, respectively. This gradient coil was systematically evaluated by testing two-dimensional (2D) and three-dimensional (3D) time-of flight (TOF) MR angiography sequences applied to a pulsatile flow phantom simulating a carotid stenosis and the intracranial vasculature. When standard 2D and 3D TOF MR angiography techniques were used to image the carotid stenosis model, dramatic signal loss in the stenotic segment and a large flow void distal to the stenosis were seen. The shorter (3.8 msec) absolute echo times (TEs) achievable with the gradient coil in 3D sequences substantially reduced the phase dispersion and associated signal loss in the region of stenosis. Shorter TEs alone (3.2 msec) did not minimize signal loss, and first-order flow compensation in the read and section-select directions provided further improvements (despite slightly longer TEs). Reduction of TEs in 2D sequences yielded relatively poor results regardless of the refocusing scheme or TE. This study confirms the predicted benefits of a dedicated coil with improved gradient capabilities for 3D MR angiography. The study suggests the limitations of 2D TOF MR angiography in the evaluation of severe stenoses. PMID- 8448400 TI - Accuracy of phase-contrast flow measurements in the presence of partial-volume effects. AB - The accuracy of volume flow rate measurements obtained with phase-contrast methods was assessed by means of computer simulation and in vitro experiments. Factors studied include (a) the partial-volume effect due to voxel dimensions relative to vessel dimensions and orientation and (b) intravoxel phase dispersion. It is shown that limited resolution (partial-volume effect) is the major obstacle to accurate flow measurement for both laminar and plug flow. The results show that at least 16 voxels must cover the cross section of the vessel lumen to obtain a measurement accuracy to within 10%. Measurement accuracy also greatly depends on the relative signal intensity of stationary tissue and is better for laminar flow than plug flow. PMID- 8448401 TI - Analysis of MR phase-contrast measurements of pulsatile velocity waveforms. AB - Errors in the measurement of the mean velocity of pulsatile velocity waveforms with ungated phase-contrast techniques were studied theoretically and experimentally. Waveforms consisting of a constant and two sinusoidal components were analyzed. Variations in magnitude and phase of the vascular magnetic resonance (MR) signal resulted in errors, the severity of which increased when either factor increased. Magnitude variations always resulted in overestimation. The general shape of the waveform greatly influenced the error, with certain waveforms producing greater inherent error than others. Experimental measurements were performed, validating the predicted sensitivity of these errors to changes in imaging parameters, including TR and flow-encoding sensitivity. Errors generally became more severe with increased flow-encoding sensitivity. The theoretical and experimental results suggest that accurate mean velocity measurements in many vessels of the body--with acquisition times of less than 15 seconds--should be attainable with ungated imaging techniques and with careful selection of relevant imaging parameters. PMID- 8448402 TI - MR detection of quantitative and structural changes in human aortic aneurysms. AB - Collagen is a major component of the extracellular matrix and a determinant of the elastic behavior of the human aorta. To investigate the changes found in aneurysmal degeneration, the authors studied the solid-state hydrogen-1 nuclear magnetic resonance line shape of collagen in aneurysms and normal human aortas. A three-component decomposition of the free induction decay was performed, with collagen characterized by a T2 of about 18 microseconds. The second moment of the collagen line shape was found to be increased in aneurysms (5.3 vs 4.8 G2), while, correspondingly, the T2 of collagen was lower in aneurysms (16.3 vs 17.7 microseconds). This corresponds to a modification of collagen structure and molecular motion. Collagen concentration was lower in nondiseased aortic walls (9.4% vs 7.3%). These results are discussed in reference to the contradictory conclusions in the current literature. The increase in collagen and the modification of its structure and molecular motion are explained by the need to resist an increasing tangential tension due to increased aortic diameter and diminished wall thickness in aneurysms and by intercalation or site binding in the helices or electric dipolar interactions in the less mobile side groups. PMID- 8448403 TI - Characterization of atherosclerosis with a 1.5-T imaging system. AB - It is shown that a conventional 1.5-T magnetic resonance (MR) imaging system can help characterize some of the key components of atherosclerotic plaque ex vivo. Fresh human aorta with atheromata was suspended in solutions of agarose and manganese chloride and heated to body temperature. The specimens were imaged with modified Dixon and projection-reconstruction imaging sequences. The specimens were then examined histologically to obtain direct correlation between images, spectra, and histologic characteristics. The results show that vessel wall and plaque components can be identified by means of their MR characteristics and correlated with their histologic appearance. The authors were able to identify normal vessel wall components, such as adventitial lipids and smooth muscle. They were also able to identify and localize plaque components such as fibrous tissue, calcification, lipids, and possible areas of hemorrhage and hemosiderin deposition. PMID- 8448404 TI - Multicenter trial of automated border detection in cardiac MR imaging. AB - The purpose of the present study was to evaluate the robustness of a method of automated border detection in cardiac magnetic resonance (MR) imaging. Thirty seven short-axis spin-echo cardiac images were acquired from three medical centers, each with its own image-acquisition protocol. Endo- and epicardial borders and areas were derived from these images with a graph-searching-based method of edge detection. Computer results were compared with observer-traced borders. The method accurately defined myocardial borders in 36 of 37 images (97%), with excellent agreement between computer- and observer-derived endocardial and epicardial areas (correlation coefficients, .94-.99). The algorithm worked equally well for data from all three centers, despite differences in image-acquisition protocols, MR systems, and field strengths. These data suggest that a method of computer-assisted edge detection based on graph-searching principles yields endocardial and epicardial areas that correlate well with those derived by an independent observer. PMID- 8448405 TI - Pulsed magnetization transfer versus continuous wave irradiation for tissue contrast enhancement. AB - Pulsed magnetization transfer and continuous wave irradiation techniques are analyzed and compared for saturation efficiency and radio-frequency (RF) power requirements at 1.5 and 0.5 T. Binomial RF pulses transmitted on resonance are a more power-efficient method of exciting saturation transfer and are easily implemented with any pulse sequence. Binomial pulses selectively excite all short T2 species and behave as 0 degrees pulses for on-resonance, long T2 species. PMID- 8448406 TI - Overlapping section coverage in multisection imaging. AB - A method is proposed in which the section position for two-dimensional Fourier transform multisection imaging is advanced from one phase-encoding step to the next, so that information is sampled continuously over the total volume under observation. This "ramp scan" technique allows reconstruction of images from any arbitrary position within the sampled volume. The imaging properties depend strongly on the order of distribution of phase-encoding steps to the different section positions. In practice, images are reconstructed at each nominal position of a multisection experiment, plus at each position halfway between sections. The volume under study is thus represented by overlapping sections. The gaps between sections that arise in conventional multisection imaging--even with optimized pulse shapes--are thus avoided. This approach is applicable not only to conventional spin-echo imaging but to other techniques such as RARE (rapid acquisition with relaxation enhancement) and gradient-echo and echo-planar imaging. PMID- 8448407 TI - Accuracy and precision of MR velocity mapping in measurement of stenotic cross sectional area, flow rate, and pressure gradient. AB - Reliability of magnetic resonance (MR) velocity mapping to assess severity of stenosis was assessed in vitro. Steady flow at different flow rates through five stenoses with a central orifice area ranging from 17 to 176 mm2 was measured with velocity mapping performed perpendicular to the stenotic jet. Besides determination of the stenotic cross-sectional area and flow rate, the pressure gradient was calculated with the modified Bernoulli equation and compared with manometer measurements. Cross-sectional areas were measured with an accuracy of > or = 76%, a precision of > or = 91%, and an error of < or = 19 mm2. Flow rates had an accuracy of > or = 72%, a precision of > or = 94%, and an error of < or = 1.4 L/min. The modification of the Bernoulli equation limited its reliability to stenoses with areas of 35-113 mm2. Pressure gradients were calculated with an accuracy of > or = 80%, a precision of > or = 88%, and an error of < or = 15 mm Hg. The method was applied in a single patient with aortic stenosis and gave estimates that agreed with those obtained by heart catheterization. PMID- 8448408 TI - Society for Magnetic Resonance Imaging 1993 annual meeting. San Francisco, California, 27-28 March 1993. Abstracts. PMID- 8448409 TI - Serving a larger community of scientists. PMID- 8448410 TI - Tissue levels of retinoids in human embryos/fetuses. AB - In nonhuman vertebrate embryos, two endogenous retinoids with significant morphogenic activities have been identified thus far: all-trans retinoic acid and 3, 4-didehydroretinoic acid. To date, no information is available concerning endogenous retinoid levels in developing human embryos or fetuses. The purpose of the present study was to provide data relating to normal levels of retinoids in various human embryonic and fetal tissues at various stages of gestation measurable with HPLC techniques. Our investigations show that all-trans-retinoic acid, 13-cis-retinoic acid, retinol, all-trans-retinoyl-beta-glucuronide, and one unidentified metabolite were all present and quantifiable in several human embryos and fetuses investigated. Tissue levels of retinol were consistently much higher than those of the other three detected metabolites; 4-oxo metabolites were below the levels of detection in all samples studied. PMID- 8448411 TI - Effect of methoxychlor on ovarian steroidogenesis: role in early pregnancy loss. AB - Antifertility properties of the pesticide methoxychlor (MXC) are well documented. Administration of MXC to rats during early pregnancy impairs implantation and reduces serum progesterone. The current study was designed to examine the effect of MXC on ovarian steroidogenesis and to define the mechanism(s) by which the pesticide exerts this effect. Rats were treated with MXC at a range of doses during days 1 to 8 of pregnancy and killed on day 9. Ovaries were incubated to assess the secretion of progesterone, estradiol, and testosterone in vitro. Steroid hormones in medium and serum were measured by radioimmunoassay. Although in vivo treatment with MXC reduced serum progesterone, no effect on the ovarian secretion of progesterone was detected in vitro. Conversely, MXC had no effect on serum estradiol levels (testosterone levels were undetectable in serum), but the incubation of ovaries in vitro revealed a reduction in the rates of ovarian estradiol and testosterone secretion. PMID- 8448412 TI - Steroidogenic assessment using ovary culture in cycling rats: effects of bis(2 diethylhexyl)phthalate on ovarian steroid production. AB - In vitro ovary culture in rats was used to characterize ovarian steroidogenesis and to evaluate changes produced by in vivo exposure to bis(2 diethylhexyl)phthalate (DEHP). Steroid profiles [progesterone (P4), estradiol (E2), and testosterone (T)] from cultures of minced ovary were obtained in untreated immature and mature rats, and from mature rats treated with DEHP. A 1-h incubation without human chorionic gonadotropin (hCG) was used to produce an initial steroidogenic profile. Three 1-h incubations with hCG were used to produce a stimulated steroid profile. A combination of initial and stimulated ovarian steroid profiles was shown to correctly identify the stage of the cycle in all untreated rats, using multivariate statistical analysis. Separately, initial or stimulated ovarian steroid profiles correctly identified the stage of the cycle in more than 90% of the rats. The statistical analysis using a combination of variables (multivariate) indicated that DEHP-treated rats were significantly different (P < 0.001) from sham-treated rats. In fact, the alteration caused by DEHP in the in vitro ovarian steroidogenic profile was most apparent in rats during diestrus and estrus. In DEHP-treated rats in diestrus, ovarian steroidogenesis appeared to shift to the production of more T and more E2 than in untreated rats in diestrus. The change seen in steroid profiles in DEHP treated rats in estrus is to decreased E2 production. The steroid profile from ovary culture in conjunction with vaginal cytology was very useful in correctly identifying in vivo DEHP-treated rats, and will be a useful in vitro technique in the evaluation of ovarian toxicants in cycling females. PMID- 8448413 TI - Male mediated teratogenesis. PMID- 8448414 TI - Dose-response characteristics of neonatal exposure to genistein on pituitary responsiveness to gonadotropin releasing hormone and volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) in postpubertal castrated female rats. AB - Estrogen exposure during critical periods of development promotes androgenization of the brain, which is reflected in altered morphology, behavior, and cyclic hormone secretion in females. Previous work in our laboratory demonstrated that neonatal female rats injected with pharmaceutical or naturally occurring estrogens had decreased GnRH-induced LH secretion and increased volume of the SDN POA as 42 day castrates. The current experiment defines the dose-response characteristics of neonatal exposure to the isoflavonoid phytoestrogen genistein (G) on pituitary sensitivity to GnRH and SDN-POA volume. Litters of rat pups received subcutaneous injections of either corn oil, 1, 10, 100, 200, 400, 500, or 1000 micrograms of G on days 1 to 10 of life. The litters were ovariectomized and weaned on day 21. On day 42 blood was drawn from right atrial catheters immediately prior to, 5, 10, 15, and 30 min following a single injection of 50 ng/kg of GnRH. Only the 10 micrograms dose of G was associated with increased pituitary response to GnRH, while progressive increases in exposure levels of G were associated with decreasing LH secretion. The SDN-POA volume was increased in only the 500 micrograms and 1000 micrograms exposure groups compared to controls. The results confirm that low doses of G have nonandrogenizing, pituitary sensitizing effects, while higher doses of G mimic the more typical effects of estrogens. The use of both morphologic and physiologic end points more completely defines the reproductive consequences of environmental estrogen exposure during critical periods of CNS development. PMID- 8448415 TI - Hexachlorobenzene toxicity in the monkey primordial germ cell without induced porphyria. AB - Hexachlorobenzene is a persistent chlorinated organic chemical that has been detected in many tissues from a variety of species including human ovary and human ovarian follicular fluid. When administered in high dosage to nonhuman primates, hexachlorobenzene causes destruction of ovarian primordial germ cells in association with systemic toxicity. The purpose of these experiments was to assess relative ovarian germ cell sensitivity at much lower dosages of hexachlorobenzene that do not produce systemic effects and additionally to evaluate oocyte function by means of the response to superovulation, fertilization, and embryo cleavage during a cycle of in vitro fertilization in the cynomolgus monkey. Hexachlorobenzene in dosages of 0.1, 1.0, and 10.0 mg/kg/day was administered orally by gelatin capsule for 90 days. There was a dose-dependent accumulation of HCB in serum and other tissues without any change in the serum estradiol response to human menopausal gonadotropin, oocyte recovery, oocyte maturation, oocyte fertilization in vitro, and early embryo cleavage rate. There was a dose-related toxic effect observed in primordial germ cells at the lowest dose despite no evidence of systemic or hepatic effects. As there were no changes in the urinary porphyrin excretion, the mechanism of hexachlorobenzene ovotoxicity may be distinct from hexachlorobenzene-induced cytochrome P-450-dependent inhibition of uroporphobilinogen decarboxylase in the liver, although such intraovarian metabolism cannot be excluded. PMID- 8448416 TI - Protective action of zinc against cobalt-induced testicular damage in the mouse. AB - The purpose of this study was to determine if toxic effects of cobalt on the murine testis could be prevented by zinc, an essential metal for spermatogenesis. CD-1 male mice were administered one of the following in their drinking water: 1) 400 ppm CoCl2, 2) 800 ppm ZnCl2, 3) 400 ppm CoCl2 + 800 ppm ZnCl2, or 4) distilled water. After 13 weeks, animals were sacrificed and testes were excised, weighed, and processed for histologic study. Comparison of testicular weights revealed no difference between the control and zinc-treated groups, while there was a small but significant reduction in the zinc/cobalt-treated group, and a large reduction in the cobalt-treated group. Histologic evaluation of testes confirmed the degenerative effects of cobalt, as well as the normal morphology in the zinc-treated group. Furthermore, 90% of the animals in the zinc/cobalt treated group exhibited complete or partial protection as demonstrated by tubular morphology. This study indicates that zinc prevents cobalt-induced testicular damage. PMID- 8448417 TI - Practices of epilepsy during pregnancy: a survey of Canadian neurologists. AB - The optimal management of epilepsy in epileptic pregnancies remains controversial. We surveyed all neurologists in Canada to determine their usual practice in managing epilepsy during pregnancy. We identified 436 neurologists in the 1990 edition of the Canadian Handbook of Medical and Surgical Specialists. We mailed a questionnaire enquiring with respect to details of management of epilepsy during pregnancy to all neurologists; in the case of nonrespondents, a follow-up questionnaire was mailed eight weeks later. We achieved a 65% response rate. We found that carbamazepine was the antiepileptic drug of first choice for the management of epilepsy during pregnancy among the majority of neurologists (75%), while phenobarbital (10%) and phenytoin (11%) were recommended much less frequently. Eight percent of respondents never used polytherapy during pregnancy. Despite recent controversy over the reproductive safety of carbamazepine, monotherapy with carbamazepine is regarded by the vast majority of Canadian neurologists as the therapy of first choice for epilepsy during pregnancy. PMID- 8448418 TI - Effects of marginal and severe iron deficiency on hepatic proteins in developing rats are reversible with dietary iron repletion. AB - Transferrin, metallothionein, cytochrome P-450, and the in vitro formation of DNA benzo[a]pyrene adducts were studied in the offspring of dams that were fed diets moderately or severely deficient in iron (Fe). The study was designed to determine whether Fe deficiency-induced alterations were reversible or if they persisted with post-weaning iron repletion. Throughout gestation and lactation the dams were fed a Control diet = 120 micrograms Fe/g diet, a Marginal Iron diet = 11 micrograms Fe/g diet, or a Low Iron diet = 7 micrograms Fe/g diet. On day 14 of lactation, 4 pups per litter were killed. On day 21, the dams were killed. Half of the remaining pups in each litter were fed their respective diets until they were killed on day 42 (Marginal Iron-Marginal Iron and Low Iron-Low Iron groups). The other half were fed the Control diet (Marginal Iron-Control and Low Iron-Control groups). The dietary intake of the Restricted Fed offspring was matched to rats in the Low Iron-Low Iron group. Offspring in the iron-deficient groups had hematocrits, hemoglobin concentrations, and liver iron levels that were lower than Controls. Day 42 offspring in the iron-deficiency groups had a lower food intake and higher liver zinc and copper levels than Controls. Day 14 Marginal and Low Iron pups had liver metallothionein levels that were lower than Controls. Day 42 Restricted Fed offspring had liver metallothionein levels that were higher than all other groups. Cytochrome P-450 levels and the in vitro formation of benzo[a]pyrene-DNA adducts were higher in Low Iron-Low Iron males than in Control males. Ethoxycoumarin O-deethylase activity was higher in day 42 Low Iron-Low Iron offspring than in Controls. These results show that the iron deficiency-induced alterations were transient, reversible with iron repletion, and in the case of cytochrome P-450 and ethoxycoumarin O-deethylase activity, dependent on the age and sex of the animal. PMID- 8448419 TI - Teratogenicity study of Scutellariae Radix in rats. AB - This teratogenicity study was carried out in pregnant S.P.F. Sprague-Dawley female rats. These animals received for a period of 11 days, from day 7 to 17 of gestation, by daily oral administration, the water extract concentrates of the medicinal herb, Scutellariae Radix, at dose levels of 0.25 g/kg (group I), 12.49 g/kg (group II), and 24.98 g/kg (group III). Two-thirds of pregnant females in each group were sacrificed on day 20 of gestation and their fetuses were examined. The remaining dams were allowed to litter naturally, and postnatal development of the offspring was observed. There was a significant (P < 0.05) dose-dependent increase in the incidence of skeletal variations (presence of lumbar rib). There was also a dose-dependent increase in the incidence of abnormal urinary system (mainly dilatation of ureter) although the abnormality incidence of group III was comparable to group II. There were no significant differences between the control and treated groups in maternal body weight, intake of diet and water, efficiency of diet, hematologic values, resorbed and dead fetuses, corpora lutea, separation of eyelids, emergence of abdominal hair and incisors, traction test values, sex organ function in fetuses, and growth of fetuses. PMID- 8448420 TI - Toxicokinetics of [14C]-saligenin cyclic-o-tolyl phosphate in anesthetized male F 344 rats. AB - Saligenin cyclic o-tolyl phosphate (SCOTP) has been proposed as the active metabolite of tri-o-cresyl phosphate (TOCP), a neurotoxic organophosphate. TOCP is also toxic to the testis and SCOTP mimics some of this toxicity. The stability of SCOTP in vivo and its uptake by selected tissues has been measured. Total radioactivity and SCOTP-associated radioactivity were determined in male F-344 rats treated i.v. with 1 mg of [14C]-SCOTP/kg. The half-life of SCOTP in blood was 8.0 +/- 1.1 min. Testes, brain, and muscle had lower concentrations of [14C] SCOTP-derived radioactivity than blood. Liver and kidney had higher concentrations of radioactivity than blood. HPLC analysis of liver, kidney, testes, and blood extracts showed that 2.8, 48, 11, and 18%, respectively, of the radioactivity present at 5 min was SCOTP. The amount of SCOTP declined rapidly, and at 30 min SCOTP could be detected only in kidney. It appears that SCOTP, although reactive, has sufficient stability to be transported from organ to organ. There is no evidence, however, of active uptake of SCOTP from blood by the testes. Evidence was obtained that SCOTP may act as an alkylating agent. PMID- 8448421 TI - Clinical grading penalizes some nurses. PMID- 8448422 TI - Telephone triage: a step forward for nursing practice? PMID- 8448423 TI - Visual impairment among older people. AB - Visual impairment is the most age-related disability, with older people forming the majority of the visually disabled population. This article re-examines the nature of visual impairment among older people and points to a key role for nurses in identification and intervention. PMID- 8448424 TI - Family therapy: approaches to treatment. AB - Family therapy deals with the way that people in family groups relate to one another. In their interactions with families, nurses may be confronted with an array of therapeutic techniques. This article aims to provide a brief account of three major conceptual models of family therapy treatment. PMID- 8448425 TI - Effects and treatment of the menopause. AB - There are 10 million postmenopausal women in this country and another 250,000 join their ranks yearly. Nurses must have a good understanding of this stage of life if they are to support their patients, and allow these women to make informed choices about their own care. PMID- 8448426 TI - Nursing models fail in practice. AB - Despite an increasing academic interest in the nature of nursing models, nurses do not tend to use them in practice. This article examines the future of nursing models as a framework for delivering client care and questions their effectiveness in a practical setting. PMID- 8448427 TI - Are stoma nurses just bag handlers? PMID- 8448428 TI - Cardiopulmonary resuscitation: basic life support skills: 2. AB - In the first of this two-part series, the reasons why nurses were not prepared to take action when faced with an emergency were examined. This article takes a step by-step look at cardiopulmonary resuscitation as specified by the European Resuscitation Council. PMID- 8448429 TI - Role of ethics in modern healthcare: 1. AB - What is ethics and where does it leave the individual conscience-controlled practitioner? In this, the first of two articles on ethics in modern healthcare, the former question is examined. PMID- 8448430 TI - How to be successful when applying for a postregistration course: 3. AB - Most interview candidates are nervous; thorough preparation should raise confidence and help minimize anxiety. This article outlines the possible responses to questions that are commonly asked at interviews for places on postregistration courses. PMID- 8448431 TI - 3D triple-resonance NMR techniques for the sequential assignment of NH and 15N resonances in 15N- and 13C-labelled proteins. AB - Two new 3D 1H-15N-13C triple-resonance experiments are presented which provide sequential cross peaks between the amide proton of one residue and the amide nitrogen of the preceding and succeeding residues or the amide proton of one residue and the amide proton of the preceding and succeeding residues, respectively. These experiments, which we term 3D-HN(CA)NNH and 3D-H(NCA)NNH, utilize an optimized magnetization transfer via the 2JNC alpha coupling to establish the sequential assignment of backbone NH and 15N resonances. In contrast to NH-NH connectivities observable in homonuclear NOESY spectra, the assignments from the 3D-H(NCA)NNH experiment are conformation independent to a first-order approximation. Thus the assignments obtained from these experiments can be used as either confirmation of assignments obtained from a conventional homonuclear approach or as an initial step in the analysis of backbone resonances according to Ikura et al. (1990) [Biochemistry, 29, 4659-4667]. Both techniques were applied to uniformly 15N- and 13C-labelled ribonuclease T1. PMID- 8448432 TI - 3D 13C-15N-heteronuclear two-spin coherence spectroscopy for polypeptide backbone assignments in 13C-15N-double-labeled proteins. AB - The pulse sequence of a new constant-time 3D triple-resonance experiment, ct HA[CAN]HN, is presented. This experiment delineates exclusively scalar connectivities and uses 13C alpha-15N heteronuclear two-spin coherence to overlay the chemical shift evolution periods of the 13C alpha and 15N nuclei, thereby providing the four resonance frequencies of the alpha-proton, the alpha-carbon, the amide nitrogen, and the amide proton of a given amino acid residue in three dimensions. This experiment promises to be a valid alternative to 4D experiments, providing the same information on intraresidue polypeptide backbone connectivities in 13C-15N-double-labeled proteins. PMID- 8448433 TI - Intrinsic nature of the three-dimensional structure of proteins as determined by distance geometry with good sampling properties. AB - A protocol for distance geometry calculation is shown to have excellent sampling properties in the determination of three-dimensional structures of proteins from nuclear magnetic resonance (NMR) data. This protocol uses a simulated annealing optimization employing mass-weighted molecular dynamics in four-dimensional space (Havel, T.F. (1991) Prog. Biophys. Mol. Biol., 56, 43-78). It attains an extremely large radius of convergence, allowing a random coil conformation to be used as the initial estimate for the succeeding optimization process. Computations are performed with four systems of simulated distance data as tests of the protocol, using an unconstrained L-alanine 30mer and three different types of proteins, bovine pancreatic trypsin inhibitor, the alpha-amylase inhibitor Tendamistat, and the N-terminal domain of the 434-repressor. The test of the unconstrained polypeptide confirms that the sampled conformational space is that of the statistical random coil. In the larger and more complicated systems of the three proteins, the protocol gives complete convergence of the optimization without any trace of initial structure dependence. As a result of an exhaustive conformational sampling by the protocol, the intrinsic nature of the structures generated with distance restraints derived from NMR data has been revealed. When the sampled structures are compared with the corresponding X-ray structures, we find that the averages of the sampled structures always show a certain pattern of discrepancy from the X-ray structure. This discrepancy is due to the short distance nature of the distance restraints, and correlates with the characteristic shape of the protein molecule. PMID- 8448434 TI - Aliphatic 1H and 13C resonance assignments for the 26-10 antibody VL domain derived from heteronuclear multidimensional NMR spectroscopy. AB - Extensive 1H and 13C assignments have been obtained for the aliphatic resonances of a uniformly 13C- and 15N-labeled recombinant VL domain from the anti-digoxin antibody 26-10. Four-dimensional triple resonance NMR data acquired with the HNCAHA and HN(CO)CAHA pulse sequences [Kay et al. (1992) J. Magn. Reson., 98, 443 450] afforded assignments for the backbone HN, N, H alpha and C alpha resonances. These data confirm and extend HN, N and H alpha assignments derived previously from three-dimensional 1H-15N NMR studies of uniformly 15N-labeled VL domain [Constantine et al. (1992), Biochemistry, 31, 5033-5043]. The identified H alpha and C alpha resonances provided a starting point for assigning the side-chain aliphatic 1H and 13C resonances using three-dimensional HCCH-COSY and HCCH-TOCSY experiments [Clore et al. (1990), Biochemistry, 29, 8172-8184]. The C alpha and C beta chemical shifts are correlated with the VL domain secondary structure. The extensive set of side-chain assignments obtained will allow a detailed comparison to be made between the solution structure of the isolated VL domain and the X-ray structure of the VL domain within the 26-10 Fab. PMID- 8448435 TI - Structure refinement using time-averaged J-coupling constant restraints. AB - We describe a new penalty function for use in restrained molecular dynamics simulations which allows experimental J-coupling information to be enforced as a time-averaged, rather than instantaneous, quantity. The pseudo-energy term has been formulated in terms of a calculated J value (a measured quantity) rather than the relevant dihedral angle (a derived quantity). This accounts for the distinct non-linearity of the coupling constant with respect to either Cartesian coordinates or dihedral angles. Example simulations of the cyclic decapeptide antamanide show the procedure's ability to enforce experimental restraints while exploring a large region of conformational space and producing a relatively small disturbance of the physical force field. PMID- 8448436 TI - The use of 1JC alpha H alpha coupling constants as a probe for protein backbone conformation. AB - Simple pseudo-3D modifications to the constant-time HSQC and HCACO experiments are described that allow accurate (+/- 0.5 Hz) measurement of one bond JC alpha H alpha coupling constants in proteins that are uniformly enriched with 13C. An empirical phi,psi-surface is calculated which describes the deviation of 1JC alpha H alpha from its random coil value, using 203 1JC alpha H alpha values measured for residues in the proteins calmodulin, staphylococcal nuclease, and basic pancreatic trypsin inhibitor, for which phi and psi are known with good precision from previous X-ray crystallographic studies. Residues in alpha-helical conformation exhibit positive deviations of 4-5 Hz, whereas deviations in beta sheet are small and, on average, slightly negative. Data indicate that 1JC alpha H alpha depends primarily on psi, and that 1JC alpha H alpha may be useful as a qualitative probe for secondary structure. Comparison of 1JC alpha H alpha coupling constants measured in free calmodulin and in its complex with a 26-amino acid peptide fragment of myosin light-chain kinase confirm that the calmodulin secondary structure is retained upon complexation but that disruption of the middle part of the 'central helix' is even more extensive than in free calmodulin. PMID- 8448437 TI - Measurement of inter-glycosidic 13C-1H coupling constants in a cyclic beta(1-->2) glucan by 13C-filtered 2D (1H,1H)ROESY. AB - A method for measuring three-bond 13C-1H scalar coupling constants across glycosidic bonds in a cyclic beta(1-->2)-glucan icosamer is presented. This oligosaccharide molecule, with its high degree of symmetry, represents a particular challenge for NMR spectroscopy to distinguish inter-residue from intra residue heteronuclear coupling effects. Chemically equivalent H2 protons in adjacent glucosyl residues are distinguished on the basis of their different through-space, dipolar interactions with the anomeric protons (H1). The strong NOE contact between anomeric (H1) and aglyconic (H2') protons permits the selective observation of the inter-residue heteronuclear couplings 3JC1H2' and 3JC2'H1 in a natural-abundance 13C-omega 1-half-filtered (1H,1H)ROESY experiment. PMID- 8448438 TI - Survey of arsenic in total diet food composites and estimation of the dietary intake of arsenic by Canadian adults and children. AB - During a comprehensive total diet study extending from 1985 to 1988, foods were collected in 6 Canadian cities (in one of them, a pilot study was conducted twice). For each of the 7 collections, foods were processed into 112 composites (105 in the initial pilot trial). Total arsenic was determined in all samples. The mean, median, and range of arsenic concentrations in all samples were 73.2, 5.1, and < 0.1-4830 ng/g, respectively. Food groups containing the highest mean arsenic levels were fish (1662 ng/g), meat and poultry (24.3 ng/g), bakery goods and cereals (24.5 ng/g), and fats and oils (19.0 ng/g). The estimated daily dietary ingestion of total arsenic by the average Canadian was 38.1 micrograms and varied from 14.9 micrograms for the 1- to 4-year-old group to 59.2 micrograms for 20- to 39-year-old males. PMID- 8448439 TI - Survey of bottled drinking water sold in Canada. Part 2. Selected volatile organic compounds. AB - Selected volatile organic compound (VOC) contaminants were determined in 182 samples of retail bottled waters purchased in Canada. Samples included spring water (86) packaged in containers of polyethylene or in smaller containers of transparent plastic or glass, mineral water (61) packaged only in transparent plastic or glass, and miscellaneous bottled waters (35). Analyses were performed by 3 laboratories, each using headspace sampling and capillary gas chromatography with either mass spectrometric (1 laboratory) or flame ionization detection with mass spectrometric confirmation, if required (2 laboratories). Benzene, the contaminant of primary interest, was detected in only 1 of the 182 samples at 2 micrograms/kg. Other VOC contaminants detected (number of positive samples, average, and range of positives in micrograms/kg) included toluene (20, 6.92, 0.5 63), cyclohexane (23, 39.2, 3-108), chloroform (12, 25.8, 3.7-70), and dichloromethane (4, 59, 22-97). Cyclohexane was found in the plastic and as a migrant from the plastic in 20 samples of spring water, but it was found in only 1 of 61 mineral water samples analyzed at only 3 micrograms/kg. Chloroform was found almost exclusively in samples that could have been obtained from public water supplies. It was not found in mineral water samples, but it was found in 1 spring water sample at 3.76 micrograms/kg. The source of the toluene contamination was not known. Other VOCs detected include ethanol and limonene, associated with added flavoring; pentane, as a migrant from a foamed polystyrene cap liner; and 1,1,2,2-tetrachloroethylene in a sample of demineralized water. PMID- 8448440 TI - Aflatoxin contamination in foods and foodstuffs in Tokyo: 1986-1990. AB - Aflatoxins were determined in 3054 samples of foods or foodstuffs, including cereals, nuts, beans, spices, dairy products, dry fruits, and edible oil. Samples were collected in Tokyo from 1986 to 1990. Aflatoxins were found in rice products, adlay, corn, crude sugar, peanut products, pistachio nuts, brazil nuts, sesame products, butter beans, white pepper, red pepper, paprika, nutmeg, and mixed spices. The highest incidence of aflatoxin contamination was observed in nutmeg (80%), and the highest level of aflatoxin B1 was observed in pistachio nuts (1382 ppb). PMID- 8448441 TI - U.S. Food and Drug Administration survey of methyl mercury in canned tuna. AB - Methyl mercury was determined by the U.S. Food and Drug Administration (FDA) in 220 samples of canned tuna collected in 1991. Samples were chosen to represent different styles, colors, and packs as available. Emphasis was placed on water packed tuna, small can size, and the highest-volume brand names. The average methyl mercury (expressed as Hg) found for the 220 samples was 0.17 ppm; the range was < 0.10-0.75 ppm. Statistically, a significantly higher level of methyl mercury was found in solid white and chunk white tuna than was found in chunk light and chunk tuna. Methyl mercury level was not related to can size. None of the 220 samples had methyl mercury levels that exceeded the 1 ppm FDA action level. PMID- 8448442 TI - Assay of oxytetracycline in animal feed by liquid chromatography and microbiological plate assay. AB - In a proposed method for determining oxytetracycline (OTC) in animal feed, OTC is extracted with acidic methanol, and the extract is centrifuged and assayed by microbiological plate assay and by reversed-phase liquid chromatography (LC). Riboflavin and furazolidone elute at retention times similar to that of OTC. Successful separations are made by using both dimethylformamide and acetonitrile mobile phases. Variation between microbiological and LC results is comparable with variation within the microbiological assay. The relative standard deviation for 6 replicates of feed at the 100 ppm level is 3.6% for the LC assay and 3.1% for the microbiological assay. PMID- 8448443 TI - Extraction of light filth from oriental fish products containing spice: collaborative study. AB - A collaborative study was conducted to validate a new method for the extraction of light filth from oriental fish products containing spice. A 100 g test portion is digested by boiling in a mixture of HCl, Igepal DM-710, and CO-730. Light filth is isolated by wet-sieving on a No. 230 plain-weave sieve with Tergitol, deaeration boiling in 40% isopropanol, and extracting with mineral oil-heptane (85 + 15) and 40% isopropanol in a Wildman trap flask. Three spiking levels for rat hairs and insect fragments were used in the study. For rat hairs, recoveries at the low, medium, and high levels averaged 80.0, 71.6, and 88.0%, respectively. Recoveries of insect fragments for low, medium, and high levels averaged 87.8, 83.7, and 89.4%, respectively. The method was adopted first action by AOAC International. PMID- 8448444 TI - Extraction of light filth from oriental sauces containing soy sauce, thickeners, and spices: collaborative study. AB - Results are reported for a collaborative study of a method for the extraction of light filth from oriental sauces containing soy sauce, thickeners, and spices. A 100 g test portion is pretreated in a 2% solution of Tergitol Anionic 4 over a steam bath, and oils are removed by wet-sieving on No. 230 sieve. Filth is isolated from 40% isopropanol by using Na4EDTA and mineral oil. Average recoveries by 9 collaborators for 3 spike levels of rat hairs (5, 10, and 15) were 84, 78, and 79%, respectively; for insect fragments (5, 15, and 30), recoveries were 92, 95, and 96%, respectively. The method was adopted first action by AOAC International. PMID- 8448445 TI - Extraction of light filth from tofu: collaborative study. AB - Results are reported for a collaborative study of a method for the extraction of light filth from tofu. A 100 g test portion is digested in HCl solution with Igepal CO-730 and Igepal DM-710. Hairs and insect fragments are isolated by wet sieving on a No. 230 sieve, dispersing remaining residual product with Aerosol OT 75%, and filtering. Average recoveries by 9 collaborators for 3 spike levels of rat hairs (5, 10, 15) were 80, 78, and 84%, respectively; for 3 spike levels of insect fragments (5, 15, 30), recoveries were 97, 99, and 99%, respectively. The method was adopted first action by AOAC International. PMID- 8448446 TI - Enzymatic determination of sulfite in foods: NMKL interlaboratory study. AB - An enzymatic method for the determination of sulfite in foods was collaboratively studied in Nordic industry and government laboratories. The sulfite in liquid foods or extracts of solid foods is analyzed according to the following principle: Sulfite ions are oxidized to sulfate ions by oxygen in the presence of sulfite oxidase, thereby forming hydrogen peroxide. Hydrogen peroxide is transformed to water by reduced nicotinamide adenine dinucleotide (NADH) in the presence of NADH peroxidase. In this reaction, NAD+ is formed (and NADH is consumed) in amounts proportional to the sulfite concentration. Consumption of NADH can be measured spectrophotometrically at 340 nm. The method was collaboratively tested in 2 separate studies with high and low levels of sulfite tested. Results of both studies are reported here. The study samples consisted of potato flakes, wine, juice, and dried apples containing between 0 and about 960 mg SO2/kg. Eleven laboratories participated in the full study and analyzed 12 samples. Six laboratories analyzed 8 samples in the complementary study. Before statistical evaluation of the collaborative study data, results were adjusted for the time-dependent decrease of sulfite in the case of materials with high sulfite content (dried apples and wine). For 2 blind duplicate samples of wine containing 75 mg SO2/kg, the relative standard deviation for repeatability (RSDr, within laboratory variation) was 3.9%. Relative standard deviation for reproducibility (RSDR, between-laboratory variation) was 7.6%. For 2 samples of dried apples containing 800 and 960 mg SO2/kg, an RSDr value of 13.3% and an RSDR value of 13.9% were calculated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448447 TI - Matrix solid-phase dispersion extraction and gas chromatographic screening of 14 chlorinated pesticides in oysters (Crassostrea virginica). AB - A multiresidue isolation technique known as matrix solid-phase dispersion (MSPD) is presented for the extraction and subsequent gas chromatographic/electron capture detection (GC/ECD) determination of 14 chlorinated pesticides (alpha-BHC, beta-BHC, lindane, heptachlor, aldrin, heptachlor epoxide, p,p'-DDE, dieldrin, endrin, 4,4'-DDD, endrin aldehyde, p,p'-DDT, endosulfan sulfate, and methoxychlor) from oysters (Crassostrea virginica). Pureed whole oysters (0.5 g aliquots) are fortified with the 14 pesticides and delta-BHC, as an internal standard, and blended with 2 g C18 (octadecylsilyl)-derivatized silica. Pesticides are eluted from an extraction column composed of C18/oyster matrix blend and 2 g activated Florisil by addition of 8 mL acetonitrile-methanol (90 + 10). Then, 2 microL of the eluate is analyzed by GC/ECD. Unfortified blank controls are treated similarly. The eluate contained all the pesticide analytes and was free of interfering coextractants. Correlation coefficients for the standard curves of the 14 extracted pesticides (linear regression analysis) ranged from 0.9849 to 0.9980. Average relative percent recoveries over the range of concentrations examined (66 +/- 12.7% to 84 +/- 25.3%, n = 25 for each pesticide), interassay variability (13.6 +/- 8.8% to 30.2 +/- 9.1%, n = 25 for each pesticide), and intra-assay variability (5.8-11.8%, n = 5 for each pesticide) indicated that the MSPD methodology successfully extracted and determined the 14 chlorinated pesticides in oyster at levels of 31.3-500 ng/g. PMID- 8448448 TI - Determination of organic pollutants in reagent water by liquid-solid extraction followed by supercritical fluid elution. AB - A selected group of polynuclear aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), organochlorine pesticides, and phthalate esters in reagent water containing no particulate matter were separated and identified by liquid solid extraction and supercritical fluid extraction (SFE). The water sample is first passed through a cartridge or disk containing a solid matrix coated with a chemically bonded C18 organic phase capable of extracting those organic compounds. The cartridge or the disk is then eluted with supercritical carbon dioxide to remove the compounds from the sorbent. Finally, the extract is injected into a capillary column gas chromatographic/quadruple mass spectrometric system. The precisions, percent recoveries of analytes using solvent elution, and percent recoveries using SFE are compared. The total analysis time is greatly reduced by using disk extraction and SFE in place of cartridge extraction and liquid-solvent elution. In addition, the waste solvent generated was minimized by using SFE. PMID- 8448449 TI - Determination of cymiazole residues in honey by liquid chromatography. AB - A liquid chromatographic method is described for the determination of cymiazole residues in honey. This acaricide is determined on a reversed-phase (C18) column, with a CH3CN-0.001N HCl-NaCl mixture (950 mL + 50 mL + 0.3 g/L) as the mobile phase, and UV detection at 265 nm. Cymiazole is extracted with n-hexane from aqueous alkalinized (pH 9) honey solutions. No further cleanup of the honey extract was required before chromatographic analysis. Recoveries on control samples fortified with 0.01, 0.10, and 1.00 ppm cymiazole ranged from 92 to 102%. The limit of determination was 0.01 ppm. PMID- 8448450 TI - Drug smuggler's delirium. PMID- 8448451 TI - Closing mental hospitals. PMID- 8448452 TI - Complaints by patients. PMID- 8448453 TI - Paradoxical pain. PMID- 8448454 TI - Workfare and health. PMID- 8448455 TI - No new AIDS virus, say scientific reviews. PMID- 8448456 TI - Incidence of severe acute renal failure in adults: results of a community based study. AB - OBJECTIVE: To determine the age related incidence of severe acute renal failure in adults in two health districts in England. DESIGN: Prospective study of patients identified as having severe acute renal failure within a two year period; subsequent monitoring of outcome for a further two years. SETTING: Two health districts in Devon. SUBJECTS: Those adults in a population of 444,971 who developed severe acute renal failure (serum creatinine concentration > 500 mumol/l) for the first time during two years, with subsequent fall of the serum creatinine concentration below the index value. MAIN OUTCOME MEASURES AND RESULTS: 125 adults (140 per million total population yearly, 172 per million adults) developed severe acute renal failure, of whom 90 (72%) were over 70. Age related incidence rose from 17 per million yearly in adults under 50 to 949 per million yearly in the 80-89 age groups. In 31 patients (25%) the cause was prostatic disease, which was related to a good prognosis (84% (26) alive at three months). Overall survival was 54% (67) at three months and 34% (42) at two years and was not significantly age related. 18 per million total population yearly (22 per million adult population) received acute dialysis. Referral rate for specialised opinion was 51 per million total population yearly with an estimated appropriate referral rate of 70 per million per year. CONCLUSIONS: The incidence of severe acute renal failure in the community is at least twice as high as the incidence reported from renal unit based studies. Prostatic disease, a preventable and treatable problem, is the most common cause. Survival figures indicate that age alone should not be a bar to specialist referral or treatment. PMID- 8448457 TI - Fat and female fecundity: prospective study of effect of body fat distribution on conception rates. AB - OBJECTIVES: To study the effect of body fat distribution in women of reproductive age on fecundity. DESIGN: Prospective cohort study of all women who had entered a donor insemination programme. SETTING: One fertility clinic serving a large part of the midwest of the Netherlands. SUBJECTS: Of 542 women attending the clinic for artificial insemination for the first time, 500 women were eligible for study. MAIN OUTCOME MEASURES: Probability of conception per cycle and number of insemination cycles before pregnancy or stopping treatment. RESULTS: A 0.1 unit increase in waist-hip ratio led to a 30% decrease in probability of conception per cycle (hazard ratio 0.706; 95% confidence interval 0.562 to 0.887) after adjustment for age, fatness, reasons for artificial insemination, cycle length and regularity, smoking, and parity. Increasing age was significantly related to lower fecundity (p < 0.05); very lean and obese women were less likely to conceive (p < 0.10) as were women with subfertile partners (p < 0.10). All other exposure variables were not significantly related to fecundity. CONCLUSIONS: Increasing waist-hip ratio is negatively associated with the probability of conception per cycle, before and after adjustment for confounding factors. Body fat distribution in women of reproductive age seems to have more impact on fertility than age or obesity. PMID- 8448458 TI - Diary keeping in asthma: comparison of written and electronic methods. AB - OBJECTIVE: To determine the extent to which symptom diaries of asthmatic patients are inaccurate or based on retrospective recall. DESIGN: Comparison of electronic and pencil and paper diaries. Both forms were completed twice daily at home for 14 days. SETTING: Outpatient clinic. SUBJECTS: 24 asthmatic outpatients also tested for severity of asthma and for anxiety. RESULTS: More sessions were missed in the evening than in the morning for both types of diaries. Significantly more retrospective entries were made in the evening (26 entries, 14 patients) than in the morning (6 entries, 3 patients). Discrepant entries of peak expiratory flow accounted for 15% of those made on the appropriate day, and three quarters of patients made at least one discrepant entry. Variation in peak expiratory flow was significantly related to number of discrepancies and number of missing days, and anxiety score was significantly related to number of missing days. About a fifth of written entries may have errors. CONCLUSION: Poor diary completion may result from having unreasonable expectations of patients and giving incomplete instructions. Electronic, time coded diaries could ensure better quality of records. PMID- 8448459 TI - Diagnosis and management after life threatening events in infants and young children who received cardiopulmonary resuscitation. AB - OBJECTIVE: To determine the mechanisms and thereby appropriate management for apparent life threatening events treated with cardiopulmonary resuscitation in infants and young children. DESIGN: Prospective clinical and physiological study. SETTING: Royal Brompton Hospital or in patients' homes, or both. SUBJECTS: 157 Patients referred at median age 2.8 months (range 1 week to 96 months), 111 (71%) had recurrent events, 44 were born preterm, 19 were siblings of infants who had died suddenly and unexpectedly, and 18 were over 12 months old. INTERVENTIONS: Multichannel physiological recordings, including oxygenation, in hospital (n = 150) and at home (n = 61). Additional recordings with electroencephalogram, video, or other respiratory measures were used to confirm diagnoses. Management involved monitoring of oxygen at home, additional inspired oxygen, anticonvulsant treatment, or child protection procedures. MAIN OUTCOME MEASURES: Abnormalities on recordings compared to published normal data and their correlation with clinical events; sudden death. RESULTS: 53 of 150 patients had abnormalities of oxygenation on hospital recordings, 28 of whom had an accompanying clinical event. Home recordings produced physiological data from 34 of 61 patients during subsequent clinical events. Final diagnoses were reached in 77 patients: deliberate suffocation by a parent (18), hypoxaemia induced by epileptic seizure (10), fabricated history and data (Munchausen syndrome by proxy; seven), acute hypoxaemia of probable respiratory origin (40), and changes in peripheral perfusion and skin colour without hypoxaemia (two). Four patients died: three suddenly and unexpectedly (none on home oxygen monitors) and one from pneumonia. CONCLUSIONS: Identification of mechanisms is essential to the appropriate management of infants with apparent life threatening events. PMID- 8448460 TI - Effects of self monitoring of triglyceride concentrations in non-insulin dependent diabetes. PMID- 8448461 TI - Estimating urinary albumin excretion rate of diabetic patients in clinical practice. PMID- 8448462 TI - Prevalence of procedures in childbirth. PMID- 8448463 TI - Comparison of prescribing unit with index including both age and sex in assessing general practice prescribing costs. AB - OBJECTIVE: To examine and compare the prescribing unit and a new prescribing index adjusting for age and sex in assessing general practice prescribing. DESIGN: Analysis of all prescriptions issued by two practices in one year. Use of data to derive a prescribing index adjusting for age and sex. Comparison of effect of prescribing unit and new index on relation between 80 practices' prescribing data and family health services authority average. SETTING: Newcastle and Gateshead Family Health Services Authorities. Two urban practices with eight doctors and combined list size of 16,300 patients. MAIN OUTCOME MEASURES: Cost and number of prescriptions issued to each age and sex group. Effect of index on relation between practice data and family health services authority average. RESULTS: The number of items prescribed and total costs rose with age. Although total costs were greater for women than for men, individual items cost more for men aged 25-84. Comparison of data adjusted by the prescribing unit and the new index with authority averages produced no significant differences except in a few practices with skewed age-sex demography. Results with the two indexes differed by over 5% in 34% (27/80) of practices for costs and in 14% (11/80) for items prescribed. CONCLUSIONS: The age and sex profile of a practice does not explain interpractice variation in prescribing patterns. Other unidentified factors need to be considered. PMID- 8448464 TI - What proportion of congenital abnormalities can be prevented? AB - OBJECTIVE: To estimate the proportion of preventable congenital abnormalities in Hungary. DESIGN: Analysis of available Hungarian data-bases and of the effectiveness of primary, secondary, and tertiary preventive methods. SETTING: Databases of ad hoc epidemiological studies and of the Hungarian congenital abnormality registry. MAIN OUTCOME MEASURES: Prevalence at birth and prevalence after prevention in 73 congenital abnormality types or groups. RESULTS: Preventive methods are available for 51 (70%) of the 73 congenital abnormality types or groups evaluated. The birth prevalence of all congenital abnormalities could be reduced from 65 to 26 per 1000; thus 39 per 1000 (60%) are preventable. Without congenital dislocation of the hip, which is unusually common in Hungary, the preventable proportion of congenital abnormalities is 52%. CONCLUSION: Many congenital abnormalities can be prevented, but as they do not represent a single pathological category there is no single strategy for their prevention. PMID- 8448466 TI - Pituitary imaging is essential for women with moderate hyperprolactinaemia. PMID- 8448465 TI - Health care in Brazil. AB - Brazil has great geopolitical importance because of its size, environmental resources, and potential economic power. The organisation of its health care system reflects the schisms within Brazilian society. High technology private care is available to the rich and inadequate public care to the poor. Limited financial resources have been overconcentrated on health care in the hospital sector and health professionals are generally inappropriately trained to meet the needs of the community. However, recent changes in the organisation of health care are taking power away from federal government to state and local authorities. This should help the process of reform, but many vested interests remain to be overcome. A link programme between Britain and Brazil focusing on primary care has resulted in exchange of ideas and staff between the two countries. If primary care in Brazil can be improved it could help to narrow the health divide between rich and poor. PMID- 8448467 TI - ABC of sleep disorders. Practical management of insomnia: behavioural and cognitive techniques. PMID- 8448468 TI - Re-emergence of tuberculosis. PMID- 8448469 TI - Re-emergence of tuberculosis. PMID- 8448470 TI - Re-emergence of tuberculosis. PMID- 8448471 TI - Re-emergence of tuberculosis. PMID- 8448472 TI - Diagnostic dilatation and curettage. PMID- 8448473 TI - Diagnostic dilatation and curettage. PMID- 8448474 TI - Diagnostic dilatation and curettage. PMID- 8448475 TI - Health promotion in schools. PMID- 8448476 TI - Health promotion in schools. PMID- 8448477 TI - Lumbar puncture in acute bacterial meningitis. PMID- 8448478 TI - Organ donation. PMID- 8448479 TI - Organ donation. PMID- 8448480 TI - Death rate from asthma. PMID- 8448481 TI - Death rate from asthma. PMID- 8448482 TI - Epidural analgesia in labor. PMID- 8448483 TI - Thromboembolic complications of laparoscopic cholecystectomy. PMID- 8448484 TI - Consent for surgery for psychiatric patients. PMID- 8448485 TI - Receiving new patients' notes from FHSAs. PMID- 8448486 TI - Shetland oil spill. PMID- 8448487 TI - The future of FHSAs. PMID- 8448488 TI - The future of FHSAs. PMID- 8448489 TI - The future of FHSAs. PMID- 8448490 TI - The future of FHSAs. PMID- 8448491 TI - The future of FHSAs. PMID- 8448492 TI - The future of FHSAs. PMID- 8448493 TI - The future of FHSAs. PMID- 8448494 TI - Mozart's scatological disorder. PMID- 8448495 TI - Mozart's scatological disorder. PMID- 8448496 TI - Mozart's scatological disorder. PMID- 8448497 TI - The rescuers. PMID- 8448499 TI - The case for collaboration. PMID- 8448498 TI - Effects on mortality of alcohol consumption, smoking, physical activity, and close personal relationships. AB - The study analyses the risks of mortality associated with alcohol consumption and smoking, as well as possible counteracting effects of physical activity and social support through close personal relationships. Data are based on the Upper Bavarian Study, a longitudinal epidemiological study of a representative community sample (n = 1668) in a rural area. Extensive semistructured psychiatric interviews by research physicians were conducted between 1975 and 1977 (n = 1536). Thirteen years after psychiatric assessment, information was obtained from the community register concerning death in the interval, data of death and cause of death according to ICD 9. This information could be ascertained for 93.1% (n = 1430) of those who had been interviewed, thus providing a good basis for generalizing the findings. Results indicate that alcohol intake and cigarette smoking increased mortality while physical activity and the availability of a steady partner had protective effects. There were no interactive effects between the four variables studied, except for a dramatically increased risk for women drinking more than 20 ml of pure alcohol a day and reporting no physical exercise at wave one assessment. The relative risks of alcohol intake and smoking, and the counteracting effects of physical activity and partnership, are exemplified in the cases of a 40-year-old female and a 40-year-old male. Specific analyses of the relationship between alcohol consumption, smoking, physical exercise and personal relationships, on the one hand, and, on the other, different causes of death, are presented. PMID- 8448500 TI - Differences between smokers and never-smokers in sensitivity to nicotine: a preliminary report. AB - Sensitivity to nicotine was explored using test doses administered via intra nasal aerosol in 10 smokers and 10 never-smokers. Smokers received 1.50 mg nicotine (in 2 sprays, < 5 seconds apart, one spray per nostril); never-smokers received either 0.50 mg (n = 3) or 0.25 mg (n = 7) nicotine. Accumulation of nicotine in plasma, per unit dose administered, was nearly four times greater in never-smokers than in smokers, indicating differences in pharmacokinetic tolerance. To examine sensitivity to nicotine without this confound, peak physiological reactivity (heart rate and blood pressure changes) was divided by peak plasma nicotine increment and the ratio was expressed as a function of cotinine level prior to dosing, thereby relating sensitivity to nicotine to history of exposure. In smokers, functional sensitivity to nicotine was inversely related to customary nicotine intake, replicating previous findings for light and heavy smokers. The observation that never-smokers were not much more sensitive to nicotine than light smokers is notable given the disparity in previous history of exposure. PMID- 8448502 TI - Why the alcohol industry sticks to facts, action, and commonsense rather than political rhetoric. PMID- 8448501 TI - Methadone dose and heroin use during maintenance treatment. AB - A retrospective study examined the association between methadone dose and in treatment heroin use as measured by fixed-interval urine testing in a cohort of 62 patients admitted to an Australian maintenance program. Urinalysis and methadone dose data were collected on subjects for a maximum two years and were analysed using Zeger & Liang's (1986) method for modelling longitudinal data. While allowing for patient descriptors and the time period in which urine samples were collected, the relative odds of using heroin were reduced by 2% for every 1 mg increase in the maintenance dose of methadone. It is estimated that the odds of patients maintained on 40 mg of methadone using heroin were 2.2 times those of patients maintained on 80 mg. PMID- 8448503 TI - Attitude of the Norwegian population to drug policy and drug-offences. AB - A national survey on people's conceptions of various intoxicants and their attitudes towards such substances shows a high degree of support in Norway for the current very restrictive drug policy. Only 6% were in favour of a more liberal practice with regard to use of cannabis. The attitudes had changed little from 1968, when a similar study was carried out. Even a majority of those who reported having used cannabis themselves said that all use should be prohibited. A comparison of the crime of possessing quite a small quantity of cannabis with other commonplace violations of the law showed that the drug offence was considered a serious crime. Although the penalties for drug offences have been raised dramatically several times since the end of the 1960s, a majority still said that the punishment prescribed by the Norwegian law for being involved with drugs is too mild. PMID- 8448504 TI - Patterns of alcohol consumption: beverage effects on gender differences. AB - This Data Note reports findings from 22,102 current drinkers who responded in the US National Interview Survey in 1988. Mean estimated alcohol intake of males exceeded that of females by a factor of two. Males drank more per occasion (ratio 1.45) and drank on more occasion (1.41). Mean ethanol content per drink was slightly less for males (ratio 0.95) attributable to a decreased proportion of drinks being wine and liquor. When beverage preferences were taken into account, the drinking patterns of males and females showed no meaningful differences among persons with similar levels of overall ethanol intake. The results do not support the view that the difference between ethanol consumption of males and females are due primarily to males drinking more per occasion. Apparent differences in drinking patterns are attributable to differences in preferred beverage. PMID- 8448505 TI - Rhetoric or realistic objectives? PMID- 8448507 TI - HIV and AIDS education. PMID- 8448506 TI - AIDS prevention. PMID- 8448508 TI - Heart and heed. PMID- 8448509 TI - Implementing alcohol policy. PMID- 8448510 TI - The alcohol industry and other 'friends'. PMID- 8448511 TI - Warning: the alcohol industry may not be your enemy. PMID- 8448512 TI - What would a friendly alcohol industry look like? PMID- 8448513 TI - Are our friends in the alcohol industry there when we need them? PMID- 8448514 TI - Behavioural correlates of alcohol intoxication. AB - Alcohol is used in most cultures despite knowledge of the physical, psychological and social problems associated with its abuse. Behavioural impairment is a function of several factors, including blood alcohol concentration (BAC) and the rate of alcohol metabolism by alcohol dehydrogenase and the microsomal ethanol oxidizing system. Their availability and activity depend upon alcohol use history, ethnicity, other drug use and gender. Adverse social consequences related to alcohol intoxication include impaired driving, acts of aggression and violence towards self and others, and various types of accidents. About 40% of all fatal traffic accidents in Canada and the US in 1986-1987 were alcohol related. Similar statistics have been reported in the UK and Europe (e.g. Sweden). The risk of a fatal car accident increases exponentially with a driver's BAC, prompting recommendations to lower the legal BAC limit for driving and piloting aircraft. Risks of falls, drownings, and fires and burns may also be increased by alcohol intoxication. At least 22% of work-related accidents may have involved alcohol use. These data are probably conservative estimates as under-reporting of alcohol use is likely. Alcohol facilitates aggressive behaviours, but it is difficult to separate the pharmacological effect from psychosocial effects or some other common factor (e.g. low CSF levels of the serotonin metabolite 5-H1AA have been reported in alcoholics, suicide attempters, violent offenders). In addition, alcohol interacts with other drugs to increase or decrease their behavioural and therapeutic effects. An acutely high BAC inhibits the metabolism of other CNS depressants (e.g. benzodiazepines), but long term alcohol use increases the metabolism of most drugs. A potential amethystic agent, to block or reverse alcohol's effects, has been identified in preclinical studies (Ro15-4513, an imidazobenzodiazepine). Some clinical studies indicated that naloxone, lithium, ibuprofen, zimeldine and catecholamine agonists may reduce ethanol-induced behavioural or cognitive effects but the results have not been consistently replicated. More research is needed to determine the potential clinical use of amethystic agents and other pharmacotherapies in the prevention and treatment of problem behaviours associated with alcohol abuse and intoxication. PMID- 8448515 TI - Policies to halve smoking deaths. AB - Britain still has amongst the highest mortality rates in the world for all the major smoking diseases. A third of all adults smoke cigarettes regularly and smoking causes one third of UK deaths in middle age. This paper discusses factors related to changes in smoking levels and concludes that without the intervention of government policies, smoking prevalence and the amount smoked per smoker is likely to rise, particularly for young people. Measures to reduce smoking are surveyed and estimates made of the maximum likely effects from health education, advertising control, general practitioner smoking cessation advice and public and work place policies. A pricing policy is suggested which, with the other policies could reduce cigarette consumption by a half so that only one in five adults smoke by the year 2000. Predictions are made of the effect of this policy package on lives and life years saved. Within twenty five years there would be 50,000 fewer deaths from smoking and half a million life years saved annually. This would rise to two thirds of a million within forty years. Deaths from lung cancer would fall by 38%. The quality of these life years saved would tend to the average for their age. PMID- 8448516 TI - The survival roles of children of alcoholics: their measurement and validity. AB - Scales to measure five survival roles proposed by Black (1979) and Wegscheider (1976) as characteristic of children of alcoholics were developed and tested among a sample of 112 adolescents. Scales representing the lost child, the acting out child, and the mascot were highly intercorrelated, but use of the placater role was relatively unrelated to the other roles. The relationship between parental drinking and role use was examined using hierarchical multiple regressions which controlled for sex, age and three family variables, intimacy, deliberateness and cohesiveness. Parental alcoholism contributed to children adopting the acting out role, did not contribute to explaining variation in the lost child and mascot roles, but was the sole predictor of the adoption of the responsible child role. In the case of the placater role, controlling family deliberateness led to the emergence of a previously masked relationship with parental alcoholism. The survival roles appear to be as much a response to family disorganization as to parental alcoholism. PMID- 8448517 TI - Alcohol and violence-related injuries: an emergency room study. AB - Drinking patterns, alcohol-related problems and drinking-in-the-injury event were compared between those admitted to the emergency room (ER) with and without injuries resulting from violence. A probability sample of 1770 adult casualty patients in four hospitals in a single California suburban county were breathalyzed and interviewed at the time of the ER visit. Among all males and females over 30, those with violence-related injuries were more likely than those with other injuries to have positive breathalyzer readings and to report drinking prior to the event, frequent heavy drinking, consequences of drinking, experiences associated with alcohol dependence and loss of control and prior treatment for an alcohol problem. The data suggest a need for research to test whether a brief intervention at the time of the ER visit for problem drinking or a referral for more extensive alcohol treatment can effect a reduction in alcohol related violence and other alcohol-related problems. PMID- 8448518 TI - Prevalence of volatile solvent inhalation among junior high school students in Japan and background life style of users. AB - In order to estimate the prevalence of volatile solvent inhalation among junior high school students in Japan and to assess certain characteristics of the lifestyle of these users, the authors surveyed 5240 students 12-15 years of age. This was the first major survey of the prevalence of volatile solvent inhalation among junior high school students in Japan, from the point of view of the number of subjects and schools. 1.5% of subjects were students who had inhaled solvents. The regularity of life style rhythm was more significantly disturbed in Lifetime Users than in Non-Users. School life and family life were significantly less relaxed for Lifetime Users than for Non-Users. Drinking alcohol and smoking had a strong relationship with inhaling volatile solvents. The authors suggest that greatly increasing education on the harmful effects of volatile solvents inhalation and increasing the frequency with which the entire family eats dinner together will be an effective prevention strategy in Japan. PMID- 8448519 TI - Problem solving is preferable. PMID- 8448520 TI - Predicting difficult tracheal intubation using a modified Mallampati sign: a pilot study report. PMID- 8448521 TI - The use of fiberoptic laryngoscopy for difficult intubation of the trachea. PMID- 8448522 TI - Digital video--the next thing. PMID- 8448523 TI - Airway blocks for the anesthetist: a review. AB - As with any regional technique, practice will improve the success rate as well as ability of the practitioner to provide the blocks. Despite the simplicity of the techniques, one must always keep in mind that such anesthesia blunts or eliminates sophisticated and highly effective airway protection reflexes, potentially leaving the patient at risk for aspiration or obstruction. As with other forms of regional anesthesia, airway blocks will provide the anesthetist with additional tools with which to better treat his/her patients. These tools will prove to be useful not only in the operating room setting, but also in emergency room and intensive care areas as well, and will add to the confidence and abilities of the practitioner. PMID- 8448524 TI - Anesthetic management of the asthmatic patient: a perioperative approach. AB - The patient with asthma presents an anesthetic challenge to the anesthetist. A thorough preoperative assessment, careful anesthetic planning, smooth induction, maintenance and emergence of anesthesia, and an uneventful postanesthesia recovery are essential to prevent the untoward effects of acute asthma exacerbation during the perioperative experience. Careful planning, continuous observation, and accurate diagnostic decision making are the essential components in lowering anesthetic and operative risk for patients with asthma. PMID- 8448525 TI - The use of lasers in otolaryngology. AB - Laser therapy for certain lesions of the larynx and airways has provided a useful alternative to the destructive, scar-producing surgical procedures of the past. The application of this technique requires awareness on the part of the anesthetist of the special requirements of the patient, the technology, and the surgeon. Continual vigilance, organized procedure, effective crisis management, and effective decision making are essential to providing each patient with an optimal laser experience. As our experience continues to grow, the cost-benefit aspects of laser therapy will be carefully scrutinized and will determine the future usefulness of this technique. PMID- 8448526 TI - Anesthesia malpractice--to settle or have your day in court. PMID- 8448527 TI - Masseter muscle spasm (MMS) after succinylcholine. PMID- 8448528 TI - Anesthetic drug interactions. PMID- 8448529 TI - Management of the difficult airway. PMID- 8448530 TI - Prevention and treatment of acute GvHD--new modalities. PMID- 8448532 TI - Use of an anti-interleukine 2 receptor monoclonal antibody for GvHD prophylaxis in unrelated bone marrow transplantation. GEGMO Group. PMID- 8448531 TI - Matched unrelated donor bone marrow transplantation for chronic myeloid leukaemia in chronic phase: comparison of ex vivo and in vivo T-cell depletion. AB - Between January 1985 and March 1992, 48 patients with chronic phase CML underwent BMT from volunteer unrelated donors (MUD) serologically identical at HLA-A, B and DR loci. 19 patients received donor marrow ex vivo T-cell depleted (EX-TCD) with Campath monoclonal antibodies. 29 patients received unmanipulated donor marrow with CsA/MTX GVHD prophylaxis; 28 received additional intravenous antilymphocyte therapy from day +1 to +5 (IN-TCD). Overall 26 patients survive at median follow up of 362 days; actuarial survival at 3 years is 50%. 3 patients have sustained haematological relapse; actuarial leukaemia-free survival is 38%. There is no difference in overall survival between the EX-TCD and IN-TCD groups, but primary graft failure (n = 4) occurred only in the EX-TCD group, while GVHD (grade II or greater) occurred more frequently in the IN-TCD group (61% vs. 29%, p = 0.084). The optimum method for GVHD prophylaxis in MUD BMT remains uncertain. PMID- 8448533 TI - Low incidence of GvHD and rejection after pharmacological ex vivo modulation of bone marrow in 2-3 antigens mismatched BMT. AB - 2-3 antigens mismatched BMT were performed on 32 children without a matched sibling donor. In the light of previous in vitro studies, which suggested a role of Vincristine and Methilprednisolone ex vivo treatment in modulating alloreactivity of T cells, bone marrow was treated with such a pharmacological cocktail before being infused. Acute GVHD 2 degrees to 4 degrees degree occurred in 46% of cases, chronic GVHD in 28%, graft failure in 13%. There was no significant difference between 2- and 3-antigens mismatched BMT as far as GVHD and graft failure are concerned. PMID- 8448534 TI - Fetal liver transplantation: biology and clinical results. AB - Over the last 18 years, we have developed the transplantation of fetal liver cells to treat severe immunodeficiencies, hematological disorders and inborn errors of metabolism. Post-natally, this treatment is successful in two-third of patients and it is therefore very valuable, especially when there is no perfectly matched donor for a bone marrow transplant. Since 1988 we have carried out these fetal liver transplants (FLTs) in utero, immediately after prenatal diagnosis. Engraftment and reconstitution have been obtained, and several advantages appear to be associated with in utero FLT: increased probability of graft take, ideal isolation of the patient (in the maternal uterus) and optimal environment for the differentiation of the transplanted fetal liver cells (in the fetal host). PMID- 8448535 TI - Cryopreservation of fetal stem cells. AB - Fetal liver cells may be transplanted, in utero, to treat disorders affecting the hematopoietic system. Conventional immunological methods were employed to determine whether pooled cryopreserved cells could be a suitable basis for a tissue bank. We found that cryopreservation did not adversely change the population, viability or immunological capacity of human fetal liver cells and therefore, pooled and cryopreserved fetal stem cells may be suitable for transplantation. PMID- 8448536 TI - Gene transfer and bone marrow transplantation with special reference to Gaucher's disease. AB - Gene therapy following gene transfer into hematopoietic cells is now being investigated for several genetic disorders (1). The candidate diseases under consideration and active experimental investigation are disorders that can be fully or partially corrected by allogeneic bone marrow transplantation, where the gene defect is known and the normal gene has been cloned and characterized. Together with ADA deficiency Gaucher's disease is a leading candidate among these disorders. We have developed high titer retroviral vectors containing the glucocerebrosidase gene that can transduce murine bone marrow stem cells with high efficiency and will result in high levels of human glucocerebrosidase in macrophages of long-term reconstituted mice. "Gene therapy" for Gaucher's disease has therefore been accomplished in the mouse. We have also developed high titer amphotropic vectors containing the glucocerebrosidase gene that can transduce human CD34+ hematopoietic progenitors with a high degree of efficiency. Up to 70% of CFU-GM colonies from these infected CD34+ cells contained the transferred gene as determined by PCR. Our vectors can also correct the enzyme deficiency of hematopoietic cells from Gaucher patients following gene transfer. PMID- 8448537 TI - Laboratory procedures used to select an unrelated HLA matched bone marrow donor. AB - Selecting an HLA matched unrelated bone marrow donor is a labour-intensive step by-step procedure, with highly specialized techniques. To be successful immunohematologists and clinicians have to work closely together. Because so much is still unknown lymphocytes and serum of patient and donor should be stored to enable future analyses. PMID- 8448538 TI - The HLA DP locus in bone marrow transplantation. Probeless genomic typing of the DPB1 alleles. AB - The outcome of bone marrow transplantation has been shown to be improved by matching of the HLA class I and class II antigens. As to the HLA class II, while there is a general agreement on the relevance of HLA-DR matching, the role of other HLA class II loci remains to be established. Among these, there is a growing interest for the possible role played by the HLA-DP locus because of its extensive polymorphism. Analysis of the correlation between DP compatibility and graft survival has been so far hindered by technical difficulties. In fact, DP allelic products cannot be easily typed serologically and, at the genomic level, the standard SSO technique foresees the use of 20 labelled oligoprobes. We have recently described a simple electrophoretic technique that, applied to HLA-DPB1 locus, is at least as discriminative as oligotyping, but it does not require probes. This method is based on the changes of the suprahelical structure of HLA molecules produced by mismatched base pairs in critical positions. These conformational changes in turn produce a degree of retardation in electrophoresis which can be allele-specific. We think that this technique, which has proven to be useful in the typing of several HLA loci, is particularly suitable for this kind of study where, often, a small number of samples at a time needs to be analyzed. PMID- 8448539 TI - Characterization of pretransplant CTL activity in "perfectly matched" unrelated bone marrow donor/recipient combinations. AB - To characterize the pre-transplant cytotoxic T cell precursor (CTLp) activity of unrelated bone marrow donors towards their HLA-ABDR compatible recipients, we have established T cell clones from the primary (positive) CTLp cultures. Two "perfectly matched" oligo-typed DR/DQ identical combinations and two A/B identical, DR subtype incompatible combinations have been studied in detail. Analysis of the clones shows that in the first two combinations the alloreactivity was directed towards a subtype of A2 (A205) and a subtype of Bw60 respectively. In the other two cases, where class II incompatibilities were present, we have not yet defined the exact specificity. However, because the majority of recipient specific clones were of the CD8 phenotype, it is very likely that also in these two cases differences in class I are being recognized. PMID- 8448540 TI - Significance of MLC for BMT with serological HLA-identical related and unrelated donors. PMID- 8448541 TI - New frontiers for allogeneic bone marrow transplantation. PMID- 8448542 TI - New strategies for selection of unrelated bone marrow donors. AB - An important problem in the selection of unrelated donors for bone marrow transplantation (UD-BMT), is HLA matching, between selected donor and recipient. Serological screening, mixed lymphocyte culture (MLC), and sequence specific oligonucleotide genotyping (PCR-SSO) are the methods commonly used for typing of HLA-genes. These ways to select donor candidates are time-expensive. We set up new applications of the "fingerprinting-PCR" technique, to analyse the polymorphic second exon of DRB, DQB, DQA, DPB of HLA Class II and second exon A, B, C HLA-Class I genes, and to search for identity between patient and serologically selected unrelated donors. In an assessment of the technique, 50 normal samples, and 4 unrelated HLA-A and HLA-B serological matched patient-donor pairs were analysed for HLA polymorphic regions. In 3 of the 4 cases (UD-BMT) at least HLA-DRB mismatched different donor-transplanted patterns were identified. In all cases PCR-SSO analysis was performed as control. Based on our data, we suggest that identification of UD for allogeneic BMT should follow these steps: 1) serological HLA-Class I and II genes screening; 2) HLA-Class II DRB gene PCR fingerprinting; 3) confirmation by SSO analysis in case of fingerprinting identity. 4) HLA-Class II DQA, DQB, DPB PCR fingerprinting. Moreover, confirmation by PCR fingerprinting or protein isoelectrofocusing of HLA-Class I identity is recommended. This "strategy" may contribute to rapid and specific selection of unrelated marrow donors. PMID- 8448543 TI - Bone marrow donors worldwide. PMID- 8448544 TI - The Anthony Nolan Research Centre. AB - The Anthony Nolan Research Centre maintains a register of potential bone marrow donors, recruited from throughout the United Kingdom. The panel was started in 1974 as an attempt to identify an unrelated bone marrow donor for a child, Anthony Nolan, who was born with Wiskott Aldrich syndrome. The child died in 1979 without a matching donor being found, but the recruitment of donors has continued over an 18 year period, until today the Register stands at 190,000 volunteers. PMID- 8448545 TI - National Marrow Donor Program: progress and challenges. PMID- 8448546 TI - Unrelated bone marrow transplantation in Canada, the national experience. Canadian Red Cross Society. AB - The Canadian Unrelated Bone Marrow Donor Registry (UBMDR) of the Canadian Red Cross Society (CRCS) was officially funded as of April 1, 1989 for an initial three year period with a mandate to recruit 50,000 unrelated bone marrow donors and to conduct the search activities for unrelated bone marrow donors worldwide on behalf of Canadian patients. Since February of 1988, 162 unrelated bone marrow transplants have been carried out in Canada. The registry now stands at an enrollment of 35,705 with approximately 1,200 donors being added monthly. Recruitment of unrelated bone marrow donors is now established in fourteen Canadian cities, and an active ethnic recruitment is now in progress. PMID- 8448547 TI - Cooperation between European registries. PMID- 8448548 TI - Italian Bone Marrow Donor Registry (IBMDR). PMID- 8448549 TI - Italian bone marrow donors: problems in people informing and in co-operating. PMID- 8448550 TI - Clinical problems in BMT from alternative donors. PMID- 8448551 TI - Frequency and indication of unrelated bone marrow transplants in Europe. European Group of Bone Marrow Transplantation (EBMT). AB - In 1991, 4,961 bone marrow transplants (BMT) were performed in Europe by 171 teams in 21 countries. 217 were from an unrelated donor. Two years ago, this number was 99, five years ago less than ten. Main indications for unrelated BMT were CML (115), AML (32), ALL (24), SAA (19), MDS (10). Major differences exist in the European countries with regard to the number of BMT performed per number of inhabitants and with regard to indications. The present study documents the marked increased in the use of unrelated BMT in Europe. It illustrates the need for health care strategies and for clearer definitions of indications. PMID- 8448552 TI - Alternative donor transplants for leukemia. Scientific Advisory Committee of the International Bone Marrow Transplant Registry. AB - We analyzed transplant outcome in more than 2,500 recipients of alternative donor and HLA-identical sibling transplants. These data indicate: (1) results of alternative donor transplants are inferior to HLA-identical sibling transplants; (2) zero HLA-antigen disparate unrelated and one HLA-antigen disparate related donors have comparable results; (3) amongst unrelated donors, zero and one HLA antigen disparity has comparable results; and (4), amongst related transplants, two HLA-antigen disparate transplants fare worse than one HLA-antigen disparate transplants. These data should be useful in deciding when to use an alternative donor and selecting the best donor. PMID- 8448553 TI - Unrelated donor marrow transplantation: an interim report from the IMUST Study. PMID- 8448554 TI - Bone marrow transplantation from unrelated donor in myelodysplastic syndromes. PMID- 8448555 TI - Bone marrow transplantation for leukemia utilizing HLA-matched unrelated donors. PMID- 8448556 TI - Bone marrow transplantation from unrelated donors for congenital immunodeficiencies. PMID- 8448557 TI - Allogeneic bone marrow transplantation using unrelated marrow donors. PMID- 8448558 TI - Allogeneic family-unrelated bone marrow transplantation in acute and chronic myeloid leukemia. PMID- 8448559 TI - In situ hybridization to detect chimerism and the origin of relapse in sex mismatched allogeneic bone marrow transplantation. PMID- 8448560 TI - Bone marrow transplantation from unrelated donors: the Italian experience. GITMO, AIEOP and IBMDR. AB - We report on 24 patients with leukemia (19 pts), congenital disorders (4 pts) or severe aplastic anemia (1 pt) who received bone marrow transplantation from unrelated volunteer donors in 8 Italian Institutions. All the donor/recipient pairs were serologically HLA-A,B,DR matched; MLR was non reactive in 21 out of 24 cases. Preparative regimens were in accord with standards for diagnosis and disease status and included TBI in 15 patients, busulfan in 8, cyclophosphamide alone in one patient with SAA. GvHD prophylaxis consisted of cyclosporine/methotrexate in the majority of cases; 6 patients received additional immunotherapy with anti-lymphocyte globulin and 1 patient in vivo Campath-1G. The bone marrow was T-cell depleted in 2 cases. Acute GvHD grade II IV occurred in 87% of patients (gr.III-IV: 57%) and was the main cause of death in 8 cases. Six patients (25%) survive with a median follow-up of 9 months, (16% actuarial survival at 3 years). A trend in favour of a better outcome has been found for age < 20 yrs at BMT (33% vs 22%), intensified GvHD prophylaxis (33% vs 22%) and transplants performed in more recent years (31% vs 18%). PMID- 8448561 TI - Allogeneic bone marrow transplantation in children from partially matched family donors. PMID- 8448562 TI - Bone marrow transplantation in children using "HLA-partially-matched" family donors. PMID- 8448563 TI - Biological aspects and clinical implications of GvHD. PMID- 8448564 TI - Radiopharmacological studies of 99mTc-CPI: experience with isolated rat atrial tissue. AB - Extraction, washout and chemical integrity of technetium(I) hexakis (2 carbomethoxy-2-isocyano propane), (99mTc-CPI) were evaluated in isolated contractile rat atrial tissue. 99mTc-CPI accumulated linearly over time at 32 degrees C with uptakes that were both concentration dependent and temperature sensitive. Uptake rates also increased with contractile strength, indicating a dependence of retention on metabolic status of the tissue. Retention indices showed that percent washout of 99mTc-CPI was much slower than control studies with 99mTcO4. HPLC analysis of retained radioactive products in atrial tissue showed most of the activity present as the 99mTc-CPI complex (75%). These observations in isolated rat atrial tissue help explain the interspecies differences in biodistribution of 99mTc-CPI and support the membrane potential dependent model for uptake and retention of technetium isonitrile complexes. PMID- 8448565 TI - Therapy with 125I-labelled internalized and non-internalized monoclonal antibodies in nude mice with human colon carcinoma xenografts. AB - The therapeutic effects of 125I-labelled (18-97 MBq) monoclonal antibodies (MAb) C-242, C-215 and S-S.1 were studied in nude mice with human colorectal adenocarcinoma tumours. The antibodies were administered 2 or 10-16 days after implantation of the tumour cells. The monoclonal antibody C-242 was internalized into the tumour cells, C-215 was internalized to a lower degree while S-S.1 (unspecific MAb) was not internalized at all. No enhanced therapeutic effect of 125I-C-242 was observed, as a result of Auger electrons, compared with 125I-C-215 and 125I-S-S.1. PMID- 8448566 TI - Radiation doses obtained from 99mTc-labelled human milk fat globule monoclonal antibodies. AB - Human milk fat globule (HMFG) monoclonal antibodies labelled with 123I and 111In are used for the diagnosis of ovarian and breast cancer. Methods have been developed to label HMFG with 99mTc and this study reports on the subsequent radiation dose delivered. The 99mTc HMFG1 distribution was obtained in 5 normal female baboons up to 71 h after administration. The liver, kidneys, bladder and whole body were identified as source organs and total absorbed doses for the target organs were 0.054 (kidneys), 0.013 (liver), 0.140 (bladder), 0.010 (ovaria), 0.004 (bone marrow), 0.002 (thyroid), 0.003 (heart wall), 0.017 (uterus) and 0.005 mGy/MBq (whole body). The effective dose was 0.014 mSv/MBq. PMID- 8448567 TI - 67Gallium-labeled liposomes with prolonged circulation: preparation and potential as nuclear imaging agents. AB - A method is described for 67Ga-labeling liposomes containing a polyethylene glycol coating which exhibit prolonged blood circulation, reduced liver and spleen uptake and accumulation in tumors. Applications as agents for diagnostic imaging and delivery of therapeutic agents are considered. Previous methods were adapted to compensate for the presence of low temperature phase transition phospholipids resulting in consistent loading with low levels of residual unentrapped label. PMID- 8448568 TI - Predictive estimate of blood dose from external counting data preceding radioiodine therapy for thyroid cancer. AB - Bone marrow depression following 131I therapy for metastatic thyroid cancer can occur in up to one-quarter of all patients so treated. An analysis was made of the 131I whole body (WB) retention and its relationship to activity in blood for 46 patients (45 adult, 1 adolescent in 49 total studies) to define the accuracy of utilizing WB external counting data as a predictor of blood dose in comparison to the more classical method which requires data from sequential blood samples. The mean percentage differences between blood dose estimates based on external WB counting and those calculated by the classical method lie within +/- 10%. The WB methodology provides a useful first-order approximation for hematopoietic dose estimates in adult patients undergoing 131I therapy for thyroid cancer. PMID- 8448569 TI - Myocardial accumulation of iodinated beta-methyl-branched fatty acid analog, [125I](p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP), and correlation to ATP concentration--II. Studies in salt-induced hypertensive rats. AB - This study investigates the possible relationship between myocardial [125I]BMIPP accumulation and ATP concentration, in the salt-induced hypertensive Dahl-strain rats. [125I]BMIPP accumulation in the myocardium was inversely related to the degree of hypertension. On the other hand, ATP levels increased in the myocardium of rats with higher blood pressure showing an inverse relationship with BMIPP accumulation. Further studies are required for elucidating these possible inter related phenomena. PMID- 8448570 TI - Blood volume distribution in lung injury. AB - Mild hydrochloric acid was used to induce injury in the caudal section of one lung in each of 10 dogs. 99mTc-red blood cells were injected intravenously. Blood samples were drawn prior to sacrifice. Lung and blood samples were weighed, assayed for radioactivity and dried to constant weight. Assuming a uniform hematocrit, and hence a constant density, we computed blood volumes in terms of mass. The control lung had 4.32 +/- 0.62 g of extravascular lung water (EVLW) per g of bloodless dried weight (BLDW). Injury in the other lung was characterized by an elevated average of 7.08 +/- 0.79 g of EVLW per g of BLDW. The control lung contained 2.49 +/- 0.43 g of blood per g of BLDW and the injured lung contained a reduced amount of 1.69 +/- 0.55 g of blood per g of BLDW. In 8 subjects, injured portions retained the least blood volume per g of BLDW (a limiting value of 1.43 +/- 0.47 g per g). These results support a thesis of a reduction of blood volume in an injured area. PMID- 8448571 TI - Can pharmacological intervention improve the visualization of the reticuloendothelial system using 99mTc-labeled albumin nanocolloid to that achievable with 111In-labeled granulocytes? Experimental studies in mice. AB - The use of 99mTc-colloids for bone marrow scintigraphy is limited by a high liver uptake, which hampers the evaluation of surrounding skeletal structures. In an experimental mouse system, different measures to increase the bone marrow activity in relation to the liver activity have been tested. A slightly positive, but significant, outcome was achieved by three different measures, namely fasting, pretreatment with a calcium-blocking pharmaceutical (Nimodipine) and pretreatment with large amounts of a gelatine colloid. It is concluded that the possibilities of dramatically improving the bone marrow uptake of a colloid compared to the liver are limited and not comparable to that achievable using radiolabeled granulocytes. PMID- 8448572 TI - 111Indium-F(ab)'2-NCA 102 monoclonal antibody: in vitro study of a specific agent for the detection of inflammatory foci. AB - A new antigranulocyte antibody was evaluated in vitro for the detection of inflammatory foci in man. The specificity for polymorphonuclear cells (PMN) of NCA 102, an anti-NCA 95 monoclonal IgG1, was determined with immunohistochemical and cytofluorometrical tests. Its affinity, assessed by Scatchard analysis, was 1.1 x 10(9) L/mol and the number of epitopes per granulocyte reached about 10(5). The biological properties of PMNs incubated with NCA 102 were not inhibited even when coupled with DTPA. A F(ab)'2 fragment was radiolabelled with 111Indium and incubated in the presence of whole blood. More than 65% radioactivity was selectively taken up by the PMN population. These findings indicated that NCA 102 antibody is suitable for sepsis detection. PMID- 8448573 TI - Micro-autoradiographic method to study [18F]FDG uptake in mouse tissue. AB - A new micro-autoradiographic method using 18F (half-life: 109.8 min) was developed to detect 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) in mouse tissues. A linear relationship between the number of silver grains and corresponding 18F radioactivity was observed. The half-distance of spatial resolution with 18F micro-autoradiography was about 2.1 microns. The grain number increased with exposure time until 6 h, but 7 h or longer exposure induced a characteristic latent image fading. After i.v. injection of [18F]FDG into normal mice, the highest grain level among the hippocampal regions of the brain was found in the stratum lacunosum-moleculare followed by the dentate molecular and the stratum oriens. All granular and pyramidal cell layers showed lower grain levels than neuropil fields. In the pyramidal cell fields, the CA3a contained the highest grain level and the CA4 the lowest. This method requires only 4 h exposure and can be applied to all 18F-tracers to assess the tracer-tissue association. PMID- 8448574 TI - Improved tumor localization with (strept)avidin and labeled biotin as a substitute for antibody. AB - Because of its short physical half life, the use of anti-tumor antibodies radiolabeled with 99mTc has necessitated early (i.e. 2-6 h post-administration) imaging. It is possible that at these early times localization of antibodies in certain tumors may be largely due to non-specific processes. If so, other proteins or agents may be preferred for early imaging of solid tumors. We have investigated tumor localization with labeled biotin administered subsequent to unlabeled and unconjugated streptavidin. Nude mice bearing anti-CEA tumors (LS174T) received 10 micrograms of 111In-labeled anti-CEA antibody (C110) or 111In-labeled streptavidin with sacrifice 5 h later. In an examination of pretargeting, other animals received 50 micrograms of unlabeled streptavidin followed 3 h later with 1 micrograms of 111In-labeled biotin (EB1) and sacrifice 2 h later. The biodistribution of labeled streptavidin was similar to that of labeled specific antibody except for lower blood and higher kidney levels. Tumor levels were also lower with labeled streptavidin but, because of still lower levels in liver and blood, the tumor/normal tissue ratios were improved. When unlabeled streptavidin was administered and followed by labeled biotin (pretargeting), tumor levels were further reduced modestly; however, normal tissue levels were greatly reduced such that the tumor/blood and tumor/liver ratios were 10.6 and 2.2 vs 1.5 and 0.5 for the specific antibody. Improvements were seen in all tissues sampled with the exception of kidney and muscle. A further control of labeled biotin alone (without the preinjection of streptavidin) showed minimal accumulations in all tissues with the exception of kidneys.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448575 TI - Enhanced tumor imaging with pokeweed mitogen. AB - Traditional tumor imaging with biotracer techniques relies solely on the target specificity of the biomolecule. We hypothesize that specific imaging is possible by altering the rate of tissue clearance (both normal and aberrant) of any given radiotracer. Pokeweed mitogen (PWM) as a biomodulator, represents a class of molecules which regulate cellular differentiation and cell-cell interactions and, as part of these mechanisms alter tissue clearance rates (both normal and aberrant). Utilizing the B-16/C57BL/6 model, 7 days post-transplantation (which represents log phase growth of the tumor), 10 animals were imaged following an i.v. injection of 1-2 mCi 99mTc-PWM in order to visualize the tumors and determine the optimal imaging kinetics. A specific tumor image is achieved between 120 and 240 min post-injection. In addition, tumor imaging studies using a non-tumor-specific biomolecule were conducted by injecting 19 animals i.v. with 1-2 mCi of 99mTc-human serum albumin (HSA). Twelve of these animals were given 10 micrograms of PWM i.p. at various intervals prior to the 99mTc-HAS administration. Imaging and biodistribution studies were performed at various intervals up to 2 h post-99mTc-HSA injection. A 32-59% increase in the tumor-to muscle ratio was observed in the PWM-treated animals relative to the non-treated controls. To further investigate the PWM-induced tissue clearance alteration hypothesis, tissue clearance studies using 99mTc-diethylenetriaminepentaacetic acid (DTPA) were conducted in non-tumor bearing ICR mice and the B-16/C57BL/6 tumor bearing animals. 99mTc-DTPA normal tissue clearance rates were significantly increased in the PWM treated animals relative to the non-treated controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448576 TI - Synthesis and biological evaluation of gallium polyaminothiols (PAT). AB - Two polyaminothiol ligands, one hexadentate, N,N',N"-tris[2-methyl(2 propanethiol)]-1,4,7-triazacyclononane (TACN), and another potentially heptadentate, tris[2-methyl(2-propanethiol)]aminoethylamine (TMAE), were synthesized and characterized using spectroscopic and analytical methods. Both ligands were labeled with gallium-67 at pH 3.0-3.5 in high yields. The resulting gallium chelates were lipophilic. The biodistribution studies for both the chelates showed hepatic uptake and biliary clearance. The total % ID activity for [67Ga]TACN in liver and intestine at 5 min was 33.86 increasing gradually to 61.4% at 30 min. The chelates were in vivo stable to plasma-transferrin transchelation as confirmed by scintigraphic images obtained by [67Ga]TACN in rats and by plasma incubation of the chelates. These results indicate that Ga TACN is a potentially useful tracer for hepatobiliary imaging using PET. No brain uptake was found. PMID- 8448577 TI - Abscess scintigraphy with 99mTc-human immunoglobulin (IgG) using a one-step labeling method. AB - It was shown earlier that non-specific human gamma globulin (IgG) labeled with 111In can be used as an agent for abscess localization. We describe experimental results with 99mTc-IgG in animals bearing abscesses and tumors using a one-step labeling method with 99mTc. We studied this compound in several animal models: mice bearing turpentine abscesses and subcutaneously transplanted sarcomas, in rats with turpentine or E. coli abscesses and intracerebrally implanted gliomas and in rabbits with E. coli or turpentine abscesses. Blood clearance was studied in dogs. It was found that the absolute concentration of 111In-IgG in abscess and tumor was higher than that of 99mTc-IgG. However, the abscess-to-tumor ratio was higher for 99mTc-IgG. The 99mTc-IgG images were of high quality and abscesses could be detected as early as 30 min post-injection (p.i.). It appears that 99mTc IgG has many potential advantages over 111In-IgG because of better physical properties of 99mTc, simpler preparation, lower cost and greater availability and the possibility of using higher 99mTc doses. PMID- 8448578 TI - 111In-labeled Mn-metalloporphyrin for tumor imaging. AB - We synthesized and developed a new tumor imaging agent, 111In-labeled metalloporphyrin (111In-ATN-10) which consists of a carrier (ATN-10) of the tumor imaging possessing both a non-radioactive manganese complex in the porphyrin ring and a bifunctional chelating group (DTPA) attached to its side chain. The images of the three kinds of tumors were delineated more clearly by 111In-ATN-10 than 67Ga-citrate. Moreover, there was no photosensitivity in ATN-10. 111In-ATN-10 is studied as a new tumor positive scintigraphic agent instead of 67Ga-citrate. PMID- 8448579 TI - Selective monomethylation of the primary amine function using [11C]CH3I and the N trifluoroacetyl derivative: preparation of N-[11C-methyl]chlorphentermine. AB - A simple, rapid and efficient method for the preparation of a potential brain blood-flow agent, N-[11C-methyl]-chlorphentermine ([11C]NMCP), is described. Optimization of the radiochemical yield of [11C]NMCP was accomplished by a Gabriel-like reaction which permits the transformation of a primary amine to a secondary amine through a sequence of acylation, deprotonation, monomethylation and saponification. This method precludes the formation of polymethylated by products which can reduce radiochemical yields, particularly with low specific activity 11CO2. PMID- 8448580 TI - Ramiprilat increases bradykinin outflow from isolated hearts of rat. AB - To establish that bradykinin is formed in the heart we measured bradykinin in the venous effluent from rat isolated hearts perfused with Krebs-Henseleit buffer. In addition, we examined the effect on bradykinin outflow of the angiotensin converting enzyme (ACE) inhibitor, ramiprilat. From rat isolated normoxic hearts a bradykinin outflow of 0.85 +/- 0.1 ng ml-1 perfusate g-1 wet weight was measured. Perfusion with ramiprilat increased the bradykinin concentration to 2.8 +/- 0.3 ng ml-1 perfusate g-1 wet weight. During ischaemia bradykinin outflow maximally increased 8.2 fold to 7.0 +/- 0.5 ng ml-1 perfusate g-1, and in ramiprilat-perfused hearts 5.8 fold to 16.0 +/- 1.8 ng ml-1 perfusate g-1. In the reperfusion period bradykinin outflow normalized to values measured in the respective pre-ischaemic period. The presents data show that bradykinin is continuously formed in the rat isolated heart. Ischaemia increases bradykinin outflow from the heart. Presumably by inhibiting degradation of kinins, ACE inhibition significantly increased the bradykinin concentration during normoxia, ischaemia and reperfusion. PMID- 8448581 TI - Enteral absorption of octreotide: absorption enhancement by polyoxyethylene-24 cholesterol ether. AB - 1. The somatostatin octapeptide-analogue octreotide was absorbed as an intact peptide from the gastro-intestinal tract with an absolute bioavailability of about 0.3% in rats. Administration of octreotide in the presence of polyoxyethylene (24)-cholesterol-ether (POECE) resulted in an about 23 fold increase of bioavailability. 2. In vitro studies with Caco-2 cells showed a dose dependent increase in octreotide permeation with increasing doses of coadministered POECE. The use of [3H]-polyethyleneglycol (PEG) 4000 as an extracellular marker also indicated that higher doses of POECE may partly enhance paracellular transport of macromolecules. 3. By means of fluorescence microscopy it was shown that transepithelial transport of the fluorescent octreotide analogue (4-nitrobenzo-2-oxa-1,3-diazol [NBD] labelled octreotide) was enhanced by the addition of POECE. Besides an increased enterocyte uptake, there was evidence of enhanced partition of NBD-octreotide into the intercellular space between enterocytes after co-administration of POECE. In addition, there appeared to be changes in the hepatic topographic disposition of NBD-octreotide when it was given together with POECE compared with its administration alone. 4. In a study in healthy volunteers, 16 mg POECE significantly enhanced by 8 fold the absorption of octreotide after oral administration. PMID- 8448582 TI - Localization and characterization of neuropeptide Y binding sites in porcine and human colon. AB - 1. We have used quantitative receptor autoradiography to investigate the localization and characteristics of binding sites for 125Iodine-Bolton Hunter labelled human neuropeptide Y ([125I]-BH-NPY) in porcine and human colon, and compared the binding characteristics with those found in porcine spleen. 2. Saturable, specific, high affinity [125I]-BH-NPY binding was localized to myenteric ganglia in porcine and human colons, and to submucosal ganglia in porcine colon. 3. Specific [125I]-BH-NPY binding to porcine myenteric ganglia was reversible in the presence of guanosine 5'-O-(3-thiotriphosphate) and was inhibited by related peptides with the rank order of potency; porcine NPY = human NPY = peptide tyrosine tyrosine (PYY) >> pancreatic polypeptide. 4. The Y2 selective analogue, NPY (13-36), competed for [125I]-BH-NPY binding to porcine myenteric ganglia with greater potency than the Y1 selective analogue, [Leu31, Pro34] NPY, the difference being small, but significant. 5. The characteristics of [125I]-BH-NPY binding to porcine myenteric ganglia were similar to those observed concurrently to porcine splenic red pulp. 6. The small difference in inhibitory potencies between NPY(13-36) and [Leu31, Pro34]NPY observed in this study in comparison with previous studies was not explained by differential ligand depletion during incubations, but may be due to differences in methodology between binding studies performed on tissue sections and on membranes. 7. We conclude that specific [25I]-BH-NPY binding sites are present in the myenteric and submucosal ganglia of the colon and that these sites may act as functional receptors by which NPY and PYY modulate colonic motility and electrolyte transport. PMID- 8448583 TI - Nitric oxide modulates vascular permeability in the rat coronary circulation. AB - 1. The objective of the present study was to assess whether inhibition of nitric oxide (NO) production could modulate vascular permeability in the coronary circulation in conscious rats. 2. Intravenous injection of NG-nitro-L-arginine methyl ester (L-NAME, 2 mg kg-1) resulted in a slowly developing hypertension and evoked twofold increases in vascular permeability in the left ventricle and right atrium as measured by the extravasation of Evans blue dye. Maintenance of mean arterial blood pressure at the level observed following L-NAME injection by infusion of noradrenaline (620-820 ng kg-1 min-1) did not induce significant protein extravasation in the coronary circulation. 3. L-NAME treatment markedly enhanced (up to 490%) protein extravasation both in the left ventricle and right atrium in response to platelet-activating factor (PAF, 1.9 nmol kg-1, i.v.) and endothelin-1 (1 nmol kg-1, i.v.). Noradrenaline infusion potentiated (up to 69%) endothelin-1-induced protein extravasation. The permeability effect of PAF was only slightly enhanced by noradrenaline. 4. The present findings indicate that inhibition of endogenous NO synthesis leads to an increase in protein extravasation and to potentiation of the permeability effects of PAF and endothelin-1 in the coronary circulation. These results also suggest that NO may be an important regulator of vascular permeability under physiological and pathological conditions. PMID- 8448584 TI - Dose-dependent effects of angiotensin converting enzyme (ACE) inhibitors on glomerular prostanoid production by normotensive rats. AB - 1. This study was designed to investigate whether the angiotensin converting enzyme (ACE) inhibitors, captopril, enalapril and fosinopril have a dose dependent effect on the production of prostaglandin E2 (PGE2), prostaglandin I2 (prostacyclin, PGI2) and thromboxane A2 (TxA2) by glomeruli isolated from normotensive Wistar-Kyoto rats. 2. Measurements of glomerular prostanoid production were made under basal conditions and in the presence of excess exogenous arachidonic acid. 3. All three ACE inhibitors demonstrated dose dependent effects upon glomerular prostanoid production which varied with the individual ACE inhibitor. 4. Enalapril induced a dose-dependent increase in the ratio of (PGE2 + PGI2)/TxA2, from 2.17 +/- 0.20 to 5.35 +/- 0.84 and to 10.0 +/- 1.16 with the low and high doses of enalapril respectively. In contrast, the high dose of captopril tended to reduce the ratio when compared to the low dose. 5. The results obtained in this study suggest that although all three ACE inhibitors appear to induce prostacyclin synthetase and/or modulate phospholipase A2 (PLA2) activity, these effects differ with the ACE inhibitor studied and the dose employed. 6. This study has demonstrated dose-dependent effects of three ACE inhibitors on glomerular prostanoid production which may be significant in modulating glomerular haemodynamics and growth characteristics of glomerular cells. PMID- 8448585 TI - Allopurinol and amlodipine improve coronary vasodilatation after myocardial ischaemia and reperfusion in anaesthetized dogs. AB - 1. We have assessed the effect of allopurinol, amlodipine and propranolol pretreatment on both endothelium-dependent and endothelium-independent coronary vasodilatation in vivo, by comparing pre-ischaemic responses with those measured after 60 min of coronary artery occlusion and 30 min of reperfusion in anaesthetized dogs. 2. In 15 untreated dogs ischaemia and reperfusion attenuated the increases in coronary blood flow produced by either acetylcholine (0.01-0.05 micrograms kg-1, i.a.) or glyceryl trinitrate (0.05-0.2 micrograms kg-1, i.a.), to an average of 39 +/- 4% and 42 +/- 5% of the pre-ischaemic control response, respectively (both P < 0.05). 3. In 5 dogs treated with allopurinol (25 mg kg-1, orally, 24 h previously, plus 50 mg kg-1, i.v., 5 min before occlusion), the increases in coronary blood flow after ischaemia and reperfusion (acetylcholine: 78 +/- 12%, glyceryl trinitrate: 60 +/- 3% of pre-ischaemic response) were significantly larger than post-ischaemic responses in untreated dogs (both P < 0.05). 4. Similarly, amlodipine treatment (3 micrograms kg-1 min-1, i.v., starting 90 min before occlusion) in 5 dogs improved post-ischaemic increases in blood flow (acetylcholine: 58.5%, glyceryl trinitrate: 66 +/- 6% of pre-ischaemic response, significantly greater than post-ischaemic responses in untreated dogs, P < 0.05). 5. In contrast, in a further 6 dogs pretreated with propranolol (1 mg kg-1, i.v., 30 min before occlusion,plus 0.5 mg kg-1 h-1, i.v.), blood flow responses after ischaemia and reperfusion were not different from post-ischaemic responses in untreated dogs (acetylcholine: 46 +/- 6%, glyceryl trinitrate: 46 +/ 6% of pre-ischaemic response).6. These results suggest that allopurinol and amlodipine protect against the post-ischaemic impairment of endothelium-dependent and endothelium-independent coronary vasodilatation in vivo by mechanisms additional to endothelial protection. PMID- 8448586 TI - Potentiation of aggregation and inhibition of adenylate cyclase in human platelets by prostaglandin E analogues. AB - 1. The 16-phenoxy prostaglandin E analogue sulprostone consistently potentiates primary aggregation waves induced by adenosine 5'-diphosphate (ADP), PAF and 11,9 epoxymethano PGH2 (U-46619) in platelet-rich plasma from human donors. The effect is not blocked by the TP-receptor antagonists, EP 092 and GR 32191. The high potency of sulprostone (threshold concentration = 4-10 nM) and the weak block of sulprostone potentiation by the EP1-receptor antagonist, AH 6809 (pA2 = 4.3) suggest the involvement of EP3-receptors as opposed to EP1- or EP2-subtypes. 2. Eight prostaglandin E (PGE) analogues were compared against sulprostone for their effects on PAF-induced aggregation in human platelet-rich plasma (PRP) in the presence of GR 32191 and the DP-receptor antagonist, BW A868C. PGE2 and 11-deoxy PGE2-1-alcohol showed evidence of both potentiating and inhibitory actions and butaprost showed only inhibitory activity at high concentrations. The remaining analogues always elicited potentiation, with the following potency ranking: sulprostone = 16,16-dimethyl PGE2 > MB 28767 > misoprostol > GR 63779X = 17 phenyl-omega-trinor PGE2. The results again indicate that EP3- rather than EP1- or EP2-receptors are involved. However, relative potentiating potency could be affected by differences in plasma protein binding and the very high sensitivity of the human platelet to prostacyclin (IP)-receptor-mediated inhibition (IC50 for the specific IP-receptor agonist cicaprost = 0.8 nM). 3. On human washed platelet suspensions the PGE analogues, with the exception of butaprost,inhibited the rise in adenosine 3':5'-cyclic monophosphate (cyclic AMP) induced by cicaprost (8 nM).PGE2 produced a monophasic inhibition curve (IC50 = 5.4 nM, 92% inhibition at 600 nM). The potency ranking was 16,16-dimethyl PGE2> sulprostone>MB 28767 = PGE2> misoprostol> GR 63778X>17-phenyl-w-trinor PGE2> 1 1-deoxy PGE2-1-alcohol. AH 6809 inhibited the effect of sulprostone and 17-phenyl-c-trinor PGE2 with pA2 values of 5.75 and 5.32 respectively; these values are at least one log unit lower than those found for EP1-receptor block in smooth muscle.4. There is a statistically significant correlation between IC50 values for the PGE analogues on the human platelet cyclic AMP assay and the guinea-pig vas deferens (standard EP3 preparation): slope =1.00, r = 0.80, P <0.05. However the correlation is far from ideal and GR 63779X in particular has a lower potency in the cyclic AMP assay. At this time we suggest that it is prudent to describe the human platelet receptor as 'EP3-like'.5. We believe that our results provide further evidence for linking PGE-induced potentiation of aggregation to inhibition of adenylate cyclase. Sulprostone is a suitable agonist for further study of this system and in particular the nature of the G-protein linkage(s) involved. In addition the necessity to consider potentiation of platelet aggregation in -relation to the clinical use of PGE analogues in man is emphasised. PMID- 8448587 TI - The action of SDZ 205,557 at 5-hydroxytryptamine (5-HT3 and 5-HT4) receptors. AB - 1. The interaction of the novel antagonist, SDZ 205,557 (2-methoxy-4-amino-5 chloro benzoic acid 2-(diethylamino) ethyl ester), at 5-HT3 and 5-HT4 receptors has been assessed in vitro and in vivo. 2. In guinea-pig hippocampus and in the presence of 0.4 microM 5-carboxamidotryptamine, 5-HT4-mediated stimulation of adenylyl cyclase was competitively antagonized by SDZ 205,557, with a pA2 value of 7.5, and a Schild slope of 0.81. In rat carbachol-contracted oesophagus, 5-HT4 receptor mediated relaxations were surmountably antagonized by SDZ 205,557 with a similar pA2 value (7.3). This value was agonist-independent with the exception of (R)-zacopride, against which a significantly lower value (6.4) was observed. 3. In functional studies of 5-HT3 receptors, SDZ 205,557 exhibited an affinity of 6.2 in guinea-pig ileum compared with 6.9 at binding sites labelled by [3H] quipazine in NG108-15 cells. In the anaesthetized, vagotomized micropig, SDZ 205,557 produced only a transient blockade of 5-HT4-mediated tachycardia. This contrasted with tropisetron, which was active for over 60 min after administration. The half-lives for the inhibitory responses of SDZ 205,557 and tropisetron were 23 and 116 min, respectively. 4. In conclusion, SDZ 205,557 has similar affinity for 5-HT3 and 5-HT4 receptors. The apparent selectivity observed in guinea-pig is due to the atypical nature of the 5-HT3 receptor in this species. The short duration of action of this novel antagonist may complicate its use in vivo. SDZ 205,557 should, therefore, be used with appropriate caution in studies defining the 5-HT4 receptor. PMID- 8448588 TI - Alpha-sialyl cholesterol reverses AF64A-induced deficit in passive avoidance response and depletion of hippocampal acetylcholine in mice. AB - 1. The effect of alpha-sialyl cholesterol (alpha-SC; alpha-D-N-acetylneuraminyl cholesterol) on disturbances of the central cholinergic system induced by ethylcholine mustard aziridinium ion (AF64A) and by scopolamine were studied by means of a step-down passive avoidance response and locomotor activities in mice. The levels of acetylcholine (ACh) in certain regions of the brain were measured to assess the neurochemical recovery promoted by alpha-SC. 2. Treatment with AF64A (2.5, 5 and 10 nmol, i.c.v.) impaired the 24 h retention latencies of animals in a dose-dependent manner, and scopolamine (0.5 mg kg-1, i.p.) also impaired the retention performance. Administration of alpha-SC (1 and 4 mg kg-1, p.o.) once daily for 13 days improved the retention performance in AF64A-treated animals in a dose-dependent manner, but not in the scopolamine-treated animals. 3. Treatment with AF64A (2.5, 5 and 10 nmol, i.c.v.) and scopolamine (0.5 mg kg 1, i.p.) increased vertical and horizontal locomotor activities. alpha-SC dose dependently attenuated the increase in locomotor activities induced by 2.5 nmol of AF64A, but not the locomotor activities caused by 5 or 10 nmol of AF64A, or scopolamine (0.5 mg kg-1, i.p.). 4. The deficit retention performance of AF64A treated animals was associated with depletion of ACh levels in the hippocampus, but not in the septum or cerebral cortex. Administration of alpha-SC to AF64A treated animals dose-dependently reversed the depletion of ACh levels in the hippocampus. 5. The results indicate that alpha-SC had significant effects after oral administration of AF64A-treated animals. The behavioural recovery promoted by alpha-SC may be based on the reversal of ACh depletion in the hippocampus. PMID- 8448589 TI - Interaction of selective compounds with muscarinic receptors at dispersed intestinal smooth muscle cells. AB - 1. The characterization of muscarinic receptors on single cells of the guinea-pig ileum longitudinal smooth muscle, devoid of neuronal elements, was functionally studied by estimating the affinities of muscarinic antagonists on acetylcholine induced contractions. 2. Atropine (5 x 10(-11) to 5 x 10(-6) M), 4 diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP, 5 x 10(-8) to 5 x 10(-6) M), cyclohexyl(4-fluoro-phenyl) (3-piperidinopropyl) silanol (pFHHSiD, 5 x 10(-7) to 5 x 10(-5) M) as well as pirenzepine (5 x 10(-7) to 5 x 10(-5) M) competitively antagonized the acetylcholine-dependent contractions with different affinities (atropine > 4-DAMP > pFHHSiD > pirenzepine). 3. Methoctramine (5 x 10( 7) to 5 x 10(-5) M), and AF-DX 116 (5 x 10(-6) and 5 x 10(-5) M) also showed antagonist properties but these deviated from simple competition. These compounds, which discriminate between M2 and M3 receptors, showed a potency lower than that of pirenzepine, the rank order of potencies being pirenzepine > methoctramine > AF-DX 116. When concentrations of AF-DX 116, methoctramine and pirenzepine were increased an unspecific contractile effect occurred. 4. McN-A 343, a partial agonist on intact guinea-pig longitudinal smooth muscle strips, on this preparation induced a weak contraction (about 7% in comparison to control) that was not reversed by antimuscarinic agents. 5. These data indicate that M3 rather than M2 receptor sites are present on this tissue. PMID- 8448590 TI - A comparison of the inhibitory effects of sodium nitroprusside, pinacidil and nifedipine on pressor response to NG-nitro-L-arginine. AB - 1. The inhibitory effects of sodium nitroprusside (SNP), a nitric oxide (NO) donor, on mean arterial pressure (MAP) responses to NG-nitro-L-arginine (L-NNA) (NO synthase inhibitor), angiotensin II (AII) and noradrenaline (NA) were compared with those of pinacidil (KATP channel opener) and nifedipine (L-type calcium antagonist) in conscious, unrestrained rats. 2. Intravenous bolus injections of L-NNA (1-64 mg kg-1), AII (0.02-1.28 micrograms kg-1) and NA (0.25 16 micrograms kg-1) dose-dependently increased MAP to similar maxima. Intravenous infusions of SNP (1, 4 and 16 micrograms kg-1 min-1) dose-dependently increased ED20S of L-NNA, AII and NA. However, the maximum response evoked by L-NNA, but not by AII nor NA, was dose-dependently reduced by SNP. Moreover, the inhibitory effect of SNP on the pressor response to L-NNA ceased when the infusion of SNP was terminated. 3. Pinacidil (80 micrograms kg-1 min-1 for 30 min followed by 5 micrograms kg-1 min-1) increased ED50S of L-NNA, AII and NA but did not decrease the maximum responses to any of these agents. 4. Nifedipine (1 mg kg-1 min-1) non selectively reduced maximum responses to L-NNA, AII and NA to similar levels and increased ED50S of AII and NA but not L-NNA. 5. The results show that SNP causes a selective, non-competitive and reversible inhibition of the pressor response to L-NNA. This inhibition by SNP is unlikely to be related to hypotension, the opening of ATP-sensitive potassium channels or blockade of L-type calcium channels. PMID- 8448591 TI - Pathological events in experimental acute pancreatitis prevented by the bradykinin antagonist, Hoe 140. AB - 1. In a previous investigation, Hoe 140, a specific and potent bradykinin B2 receptor antagonist, prevented the pancreatic oedema and the hypotension observed during acute experimental pancreatitis; however, it augmented the associated rises in the serum activities of pancreatic enzymes. Therefore, we have now investigated the consequences of the pancreatic oedema for the fate of activated enzymes released into the tissue during the course of acute pancreatitis. 2. Acute oedematous pancreatitis was induced in rats, pretreated with captopril (50 mumol kg-1, i.p.), by hyperstimulation of the exocrine function of the pancreas with the cholecystokinin analogue, caerulein (4 nmol kg-1 h-1, i.v.), for up to 120 min. 3. Pancreatic oedema began to develop 10 min after the start of the caerulein infusion, reached a maximum within about 45 min, and then declined slightly. The development of the oedema parallelled the second phase of the caerulein-induced fall in blood pressure found in earlier experiments. No further extravasation of plasma proteins occurred during the 2nd hour of the caerulein infusion. The oedema formation was completely blocked in animals pretreated with the bradykinin receptor antagonist, Hoe 140 (100 nmol kg-1, s.c.). Pretreatment with aprotinin or soy bean trypsin inhibitor did not result in a significant inhibition of the oedema. 4. The haematocrit of animals with experimental pancreatitis showed a pronounced increase which started 10 min after the start of the caerulein infusion and reached maximal values at 60 min. The changes in haematocrit showed a reduction in total blood volume of 28% due to a 48% loss of plasma. This effect was completely blocked by Hoe 140. 5. In rats with caerulein induced pancreatitis, there was a time-dependent increase in the activities of amylase and lipase in blood serum as well as in the pancreas. Pretreatment with Hoe 140 greatly augmented the caerulein-induced rise in enzyme activities in blood serum but potently attenuated it in the pancreas. The activities of trypsin in both the blood serum and the pancreas were below or near the limit of detection in all experimental groups.6. It is concluded that the second phase of hypotension in this model of acute pancreatitis is due to the liberation of kinins which cause a massive loss of blood plasma into the pancreas and into the retroperitoneal space. Activated enzymes are trapped in the pancreas, at least in part, by the oedema of the gland. Treatment with Hoe 140 prevents the oedema formation and greatly facilitates the egress of activated enzymes from the pancreas. PMID- 8448592 TI - Pharmacological differentiation by pertussis toxin of the in vivo acute responses to fMLP and PAF in guinea-pig lungs. AB - 1. The effects of pertussis toxin on the N-formyl-L-methionyl-L-leucyl-L phenylalanine (fMLP) and platelet-activating factor (PAF)-induced variations in pulmonary capillary albumin exchanges, blood volume, leucocyte or platelet sequestration were studied in the guinea-pig, by use of radioactive tracers. The effects of pertussis toxin on pulmonary insufflation pressure were studied in parallel. 2. The i.v. administration of fMLP and PAF to the guinea-pig was followed by bronchoconstriction, increased lung capillary albumin exchanges (vasopermeability) sequestration of leucocytes, leucopenia and reduction of blood volume (vasoconstriction). PAF also induced platelet sequestration in lungs and thrombocytopenia. 3. Pertussis toxin (10 micrograms kg-1, i.v., 72 h before the experiment) prevented all the studied fMLP-induced effects, but failed to modify PAF-induced bronchoconstriction, lung vasoconstriction, platelet sequestration, thrombocytopenia and the increased capillary vasopermeability. In the same conditions the lung leucocyte sequestration was not significantly affected when leucopenia was partially reduced. 4. It is suggested that the effects of fMLP, but not those of PAF, involve a Gi-like protein. PMID- 8448593 TI - Endothelin-1 does not mediate hypoxic vasoconstriction in canine isolated blood vessels: effect of BQ-123. AB - 1. The role of endothelin-1 in mediating the phenomenon of hypoxic vasoconstriction was examined in canine, isolated pulmonary, circumflex coronary and femoral arterial rings. 2. In tissues with an intact endothelium, the exogenous application of endothelin-1 (0.1-300 nM) caused concentration-dependent increases in canine, isolated pulmonary artery tone. Endothelin-3 (1-300 nM) was approximately 30 fold less potent than endothelin-1 as a vasoconstrictor in this tissue. In contrast, the selective ETB-receptor agonist, sarafotoxin S6c (0.01-1 microM), failed to elicit vasoconstriction in this tissue. Thus, endothelin isopeptide-induced vasoconstriction of the canine isolated pulmonary artery is mediated exclusively by the ETA-receptor subtype. 3. The concentration-dependent increases in isometric tension induced by endothelin-1 (0.1-300 nM) were antagonized by the ETA-selective antagonist, BQ-123 (10 microM); this concentration of antagonist caused a shift to the right in the concentration response curve for endothelin-1 of approximately two orders of magnitude. This concentration of BQ-123 did not unmask any ETB-receptor-mediated vasoconstriction since sarafotoxin S6c (0.01-1 microM) still failed to elicit contraction in the presence of this concentration of BQ-123. 4. The hypoxia-induced vasoconstriction of canine, isolated pulmonary, circumflex coronary and femoral arterial rings was unaffected by pretreatment with the endothelin receptor antagonist, BQ-123 (10 microM), a concentration shown previously to antagonize the contractile actions of exogenously applied endothelin-1 in the isolated pulmonary artery. 5. These results are the first to provide direct evidence showing that the endothelium dependent vasoconstriction observed during acute periods of hypoxia in vitro is not mediated by an endothelin-related isopeptide. PMID- 8448594 TI - Effects of capsaicin and 5-HT3 antagonists on 5-hydroxytryptamine-evoked release of calcitonin gene-related peptide in the guinea-pig heart. AB - 1. The effect of 5-hydroxytryptamine (5-HT) on the release of calcitonin gene related peptide (CGRP) was studied directly in the isolated perfused heart and indirectly in the isolated left atria of guinea-pig. 2. 5-HT injection into the guinea-pig isolated and perfused heart evoked a dose-dependent (1-100 microM) release of CGRP-like immunoreactivity (LI) that was abolished by in vitro pretreatment with capsaicin and was not affected by indomethacin. 3. Chlorophenyldiguanide (CPD, 100 microM), but not 8-hydroxy-dipropylaminotetralin (8-OH-DPAT, 100 microM), sumatriptan (100 microM) or 1-(2,5-dimethoxy-4 iodophenyl)-2-aminopropane (DOI, 100 microM) evoked a release of CGRP-LI. Ondansetron (10 microM) or ICS205-930 (20 microM) completely abolished the 5-HT (100 microM)-evoked CGRP-LI release. 4. In the isolated electrically driven left atria of the guinea-pig 5-HT (1-10 microM) and CPD (3-100 microM) produced a positive inotropic response, which was abolished by capsaicin pretreatment. 8-OH DPAT (10 microM) and DOI (10 microM) were inactive. Ondansetron inhibited the response to 5-HT with a pA2 of 6.50 (CL 6.08-6.91). 5. It is concluded that 5-HT causes a release of CGRP in the whole heart and a positive inotropic response in the isolated atria of guinea-pig. Both these effects are sensitive to capsaicin pretreatment and to 5-HT3 antagonists. PMID- 8448595 TI - A novel ETA-receptor antagonist, FR 139317, inhibits endothelin-induced contractions of guinea-pig pulmonary arteries, but not trachea. AB - 1. The effects of a proposed endothelin-receptor antagonist, FR 139317, on the contraction induced by endothelin-1, endothelin-2 and endothelin-3, were analysed on isolated circular segments of pulmonary arteries and rings of trachea from the guinea-pig. 2. The pharmacological profiles of endothelin-1 and endothelin-2 were almost identical in the guinea-pig pulmonary artery, whereas endothelin-3 demonstrated a weaker and less potent contractile effect. The contractions induced by endothelin-1 and endotheliln-2 were competitively antagonized by FR 139317. Schild plot analysis revealed a straight line with a slope that did not differ from unity. The pA2 value was 6.65. In contrast, the endothelin-3 induced contractile response was unaffected by FR 139317. 3. In tracheal segments endothelin-1, endothelin-2 and endothelin-3 evoked contractions of similar magnitude and sensitivity. FR 139317 had no effect on the endothelin-induced contractions in tracheal segments. 4. In ring segments of pulmonary artery and trachea, potassium, noradrenaline and histamine caused concentration-dependent contractile effects. These contractions were not modified by FR 139317 in the concentration range 10(-7) to 3 x 10(-6)M. 5. FR 139317 seems to be a selective ETA-receptor antagonist which competitively antagonizes the endothelin-1- and endothelin-2-induced contractions of guinea-pig isolated pulmonary arteries. Thus, the guinea-pig pulmonary artery appears to be endowed with one receptor type (ETA) which is antagonized by FR 139317 and with another endothelin-receptor subtype which responds to endothelin-3, but is not antagonized by FR 139317. In the trachea, all three peptides act on a homogeneous population of receptors which is unaffected by FR 139317. This suggests an ETA-receptor in the guinea-pig pulmonary artery and another receptor, probably of ETB-type, in the guinea-pig trachea. PMID- 8448596 TI - Two distinct cytosolic calcium responses to extracellular ATP in rat parotid acinar cells. AB - 1. Increasing concentrations of ATP (0.5 microM-300 microM) produced a biphasic increase in intracellular calcium concentration [Ca]i in rat parotid acinar cells, reflecting two distinct Cai responses to extracellular ATP. 2. In the absence of Mg2+ (with 3 mM CaCl2 in the buffer solution), the more sensitive response was maximal at 3-5 microM and was not further increased by 30 microM ATP. This response to ATP was not well maintained and was blocked by ADP (0.5 mM). A second, much larger increase in Cai was observed on addition of 300 microM ATP. This larger effect, which we have described previously, appears to be mediated by ATP4-, and was selectively reversed by 4,4'-di-isothiocyanato dihydrostilbene-2,2'-disulphonate as well as by high concentrations of alpha,beta methylene ATP. 3. Among ATP analogues, only the putative P2Z agonist, 3'-0-(4 benzoyl)benzoyl-ATP distinguished between the two responses. This analogue was at least 10 fold more potent than ATP in stimulating the ATP(4-)-response, but did not evoke the more sensitive response. The agonist potency series for both responses to ATP was identical for other analogues examined (ATP > ATP gamma S = 2-methylthio ATP (a P2y-selective agonist) >> ADP, ITP and alpha,beta-methylene ATP (a P2x-selective agonist)). 4. Although the effect of ATP4- could best be characterized as a P2z-type purinoceptor response, this effect was strongly and selectively blocked by reactive blue 2, a putative P2y-purinoceptor antagonist. Reactive blue 2 may bind to and block P2z purinoceptors since [gamma 32P]-ATP binding to parotid cells was inhibited by this compound. 5. In contrast to the response to ATP4-, the more sensitive response to ATP was potentiated by 2+ reactive blue 2 and was less affected by increases in external Mg2+ and Ca2+.6. Parasympathetic denervation selectively increased the more sensitive response, suggesting that it maybe physiologically regulated. PMID- 8448597 TI - Kinin-induced chloride permeability changes in colony 29 epithelia estimated from 125I- efflux and MEQ fluorescence. AB - 1. The changes in apical Cl- permeability of Colony 29 human colonic epithelial monolayers were estimated from the rate constant of 125I- efflux from tissues loaded with the isotope. 2. Forskolin was used to increase intracellular concentrations of adenosine 3:5' cyclic-monophosphate (cyclic AMP), and A23187 to increase intracellular free Ca2+ (Cai). Both treatments increased the rate constant for 125I- efflux, indicating an increase in apical Cl- permeability. 3. Lysylbradykinin (LBK) also increased the rate constant for 125I- efflux, sometimes biphasically. Chelation of intracellular Ca2+ with BAPTA or prevention of prostaglandin formation with piroxicam, attenuated but did not eliminate the effect of LBK. It is concluded that LBK affects 125I- efflux through the agency of both cyclic AMP and Ca2+. 4. Ba2+ attenuated the effect of LBK and A23187 on 125I- efflux, but had no effect on the action of forskolin. It is concluded that Ca2+ has a major effect on K+ channels, the resulting hyperpolarization increasing the driving force for 125I- efflux. A secondary effect on Ca(2+) sensitive Cl- channels is possible. By contrast, cyclic AMP exerts it major effect on apical Cl- channels. 5. Using a Cl- sensitive fluorescent dye, MEQ, the intracellular chloride concentration, Cli was estimated to be around 30 mM, which was increased to around 50 mM by forskolin, suggesting cyclic AMP could activate the Na-K-2Cl co-transporter. 6. MEQ fluorescence was used to estimate Cl- influx and efflux rates of epithelial cells. These were increased three fold by forskolin and dibutyryl cyclic AMP and two fold by LBK and histamine. 7. It is concluded that LBK increases electrogenic chloride secretion in Colony 29 epithelia through the generation of second messengers cyclic AMP and Ca2+, each of which may act on both apical and basolateral membranes. PMID- 8448598 TI - Quantitative analysis of the agonist and antagonist actions of some ATP analogues at P2X-purinoceptors in the rabbit ear artery. AB - 1. The agonist and antagonist effects of a series of beta, gamma-methylene dihalo and 2-methylthio-substituted analogues of ATP at P2x-purinoceptors have been analysed on the rabbit isolated ear artery preparation. Cumulative and sequential dosing experimental protocols were employed in the construction of agonist concentration-effect curves in order to address the possible influence of acute receptor desensitization on subsequent analyses. 2. Using the cumulative curve design the following results were obtained: D-AMP-PCBr2P, 2-methylthio-D-AMP PCCl2P, L-AMP-PCF2P, L-AMP-PCCl2P and LAMP-PCBr2P each behaved as partial agonists. D-AMP-CPP was used as a reference full agonist and these analogues were analysed by the comparative method of Barlow et al. (1967), to provide estimates of affinity and efficacy. 2-Methylthio-L-AMP-PCBr2P was virtually silent as an agonist and was analysed as a competitive antagonist by Schild analysis. 3. Two agonists, L-AMP-PCCl2P and L-AMP-PCBr2P, were analysed by the sequential curve design, and the antagonist effects of one of the agonists, L-AMP-PCBr2P were also analysed using this protocol. The resulting estimates of affinity and efficacy, while similar to those obtained with the cumulative design, indicated that acute desensitization may affect curve definition and estimation of these quantities. 4. The following structure-activity trends emerged: D-analogues tended to have higher efficacy but lower affinity than L-analogues; efficacy varied markedly and inversely with the atomic weight of the halogen while affinity was only minimally affected; 2-methylthio- substitution also reduced efficacy with minimal effect on affinity. 5. The results of this analysis are discussed in terms of the utility of affinity and efficacy information in the classification of purinoceptors and the design of chemical probes for them. PMID- 8448599 TI - In vitro characterization of prostanoid receptors on human myometrium at term pregnancy. AB - 1. Prostanoid receptors present on the pregnant human myometrium in vitro have been characterized according to the receptor classification proposed by Coleman et al. (1984) using natural prostanoids and synthetic, selective analogues and antagonists where available. 2. Prostaglandin E2 (PGE2) produced a biphasic effect consisting of an initial excitation followed by a dose-related inhibition. The EP2/EP3-receptor agonists, rioprostil and misoprostol, produced similar effects to PGE2, however, the excitatory event of the misoprostol response was related to dose. The EP1/EP3-receptor agonist, sulprostone, evoked a purely excitatory response which was unaffected by AH6809. The selective EP2-receptor agonist butaprost produced a long-lasting dose-dependent inhibition of activity. The results from these prostanoids indicated that inhibitory EP2- and excitatory EP3-receptors are present on myometrium from pregnant donors at term. 3. PGF2 alpha and the synthetic FP-receptor agonist, fluprostenol, caused equipotent excitatory effects, indicating the presence of contractile FP-receptors. 4. PGD2 produced a biphasic effect of which the inhibition appeared dose-related and was antagonized by the selective DP-receptor antagonist BW A868C. The selective DP receptor agonist, BW245C, produced a potent inhibitory effect that was competitively antagonized by BW A868C (pA2 = 8.6). 5. PGI2 produced a biphasic response qualitatively similar to PGE2. The EP1/IP-receptor agonist, iloprost, produced an occasional unquantifiable excitation and dose-related inhibition. The selective IP-receptor prostanoid, cicaprost, evoked only an inhibitory response. 6. The stable thromboxane A2 (TXA2)-mimetic, U46619, produced potent excitation which was competitively antagonized by the TP-receptor antagonist, GR32191 (pA2 = 7.2). 7. The prostanoids tested indicate that a heterogeneous population of prostanoid receptors are presen ton human myometrium from pregnant donors. It may be concluded that excitation is EP3-, FP- and TP-receptor-mediated and inhibition is EP2-, DP- and IP-receptor-mediated. Comparison of data obtained from non pregnant specimens indicates that the lower segment tissue from pregnant donors demonstrated more pronounced responses to EP2 and IP-receptor activation. PMID- 8448600 TI - Electropharmacological effects of berberine on canine cardiac Purkinje fibres and ventricular muscle and atrial muscle of the rabbit. AB - 1. Conventional microelectrode techniques were used for intracellular recordings of the transmembrane electrical potentials, the effects of berberine were studied on canine cardiac Purkinje and ventricular muscle fibres and on rabbit atrial fibres. 2. Berberine (3-30 microM) increased in a concentration-dependent manner, the action potential duration (APD) in canine Purkinje and ventricular muscle without affecting other parameters of the action potential. 3. The berberine induced enlargement of the APD showed reverse use-dependence, so that the effect was greater at lower rates of stimulation. 4. Preparations perfused with berberine (30 microM) and driven at rates below 0.5 Hz exhibited early after depolarizations which persisted 3-4 h after washing. 5. The early afterdepolarizations were reversibly abolished by perfusion with lignocaine (3 microM) or by the increase in the rate of stimulation. 6. The effective refractory period (ERP) of Purkinje fibres was greatly increased by berberine (30 microM); however, the ratio ERP/APD was not significantly affected. 7. Berberine (10-100 microM) decreased in a concentration-dependent manner the spontaneous frequency of rabbit sinoatrial cells. The decrease in frequency was accompanied by a depression of the phase 4 depolarization, without significant changes in other parameters of the nodal action potential. 8. Atropine (2.5 microM) did not affect the bradycardic effect of berberine. On the other hand, berberine (30 microM) did not alter the chronotropic effect of isoprenaline. 9. Berberine (30 microM) also increased the duration of slow responses in K-depolarized rabbit atrial muscle fibres, other parameters being unaffected. 10. It is suggested that berberine exerts Class III antiarrhythmic and proarrhythmic actions in cardiac muscle of the dog in vitro. PMID- 8448601 TI - Investigations into the mechanism of vasoconstrictor action of the topical steroid betamethasone-17-valerate in the rat. AB - 1. The effect of topical betamethasone upon skin blood flow was investigated in the rat. Two types of vasodilator stimuli were used; local heating to the surface of the skin and intradermal application of inflammatory agents. Blood flow was measured by laser doppler velocimetry. 2. Topical betamethasone-17-valerate (1 g with an 18 h pretreatment) significantly inhibited the heat-induced vasodilatation in the rat skin, as also did systemically administered betamethasone (1 mg kg-1, 3 h pretreatment). 3. Angiotensin converting enzyme (ACE) inhibitors (captopril, 5 mg kg-1 and enalapril, 1 mg kg-1, 30 min pretreatments) were the only drugs out of several different types of systemically administered inhibitors and antagonists that were tested which also inhibited the heat-induced vasodilatation. Aprotinin (100,000 KIU kg-1, 5 min pretreatment) a serine protease inhibitor, significantly potentiated the heat-induced response. 4. Bradykinin (50 nmol per site), des-Arg9-bradykinin (5 nmol per site), substance P (0.1 nmol per site) and capsaicin (1 mumol per site) induced an increase in skin blood flow. 5. Topical betamethasone treatment resulted in a significant inhibition of the vasodilator response to des-Arg9-bradykinin, whereas captopril treatment inhibited the responses to substance P, capsaicin, bradykinin and des-Arg9-bradykinin. 6. Intradermal application of captopril (10 100 micrograms) also caused a dose-dependent inhibition of the heat-induced vasodilatation. 7. These results suggest that topical betamethasone may be acting in a manner similar to that of the ACE inhibitors to produce an inhibition of the flow responses in the skin and that this effect may be brought about by interfering with the action of vasodilator peptide(s) or protein(s). PMID- 8448602 TI - Cibenzoline inhibits diazoxide- and 2,4-dinitrophenol-activated ATP-sensitive K+ channels in guinea-pig ventricular cells. AB - 1. We have investigated the effects of diazoxide (a sulphonamide derivative) and cibenzoline (a class I antiarrhythmic drug) on ATP-sensitive K+ currents in guinea-pig ventricular cells, using whole-cell clamp techniques. 2. Diazoxide (50 microM) produced a marked shortening of action potential duration which was antagonized by 1 microM glibenclamide, an ATP-sensitive K+ channel blocker. 3. Diazoxide (50 microM) increased the quasi-steady state outward current elicited by a ramp voltage protocol (-20 mV s-1) at potentials positive to about -70 mV. This effect was completely prevented in the presence of glibenclamide (1 microM), thereby suggesting that diazoxide opens ATP-sensitive K+ channels. 4. Cibenzoline (5 microM) depressed the diazoxide-induced increases in the outward current and the pretreatment with this agent prevented the development of the diazoxide induced outward current. 5. Cibenzoline (10 microM) reversed the 2,4 dinitrophenol (50 microM)-induced shortening of the action potential duration partially but significantly. 6. These results suggest that diazoxide activates ATP-sensitive K+ channels of guinea-pig ventricular cells and that cibenzoline, at therapeutic concentrations, inhibits this channel. PMID- 8448603 TI - Incomplete inhibition of the pressor effects of endothelin-1 and related peptides in the anaesthetized rat with BQ-123 provides evidence for more than one vasoconstrictor receptor. AB - 1. The effects of the ETA receptor antagonist, BQ-123 on blood pressure changes induced by various members of the endothelin (ET)/sarafotoxin (SX) peptide superfamily were investigated in the anaesthetized rat. 2. ET-1 (1 nmol kg-1, i.v. bolus) induced a sustained increase in mean arterial pressure (MAP, maximum increase 44 +/- 3 mmHg). Intravenous injection of BQ-123 at 0.2, 1.0 or 5.0 mg kg 1 5 min before ET-1 inhibited the pressor response by 18, 50 and 61%, respectively. The ET-1 pressor response was inhibited by 75% when the peptide was given 60 min after the start of a 120 min i.v. infusion of BQ-123 (0.2 mg kg-1 min-1). 3. In addition to ET-1, BQ-123 (1 mg kg-1, i.v. bolus) attenuated the pressor responses to big ET-1 (1 nmol kg-1, i.v., bolus, maximum increase in MAP: 68 +/- 7 mmHg), ET-3 (3 nmol kg-1, i.v., bolus, maximum response: 30 +/- 3 mmHg), SX6b (1 nmol kg-1, i.v., bolus, maximum response: 41 +/- 5 mmHg) and SX6c (1 nmol kg-1, i.v., bolus, maximum response: 24 +/- 4 mmHg) by 65, 60, 88 and 50%, respectively. 4. With the exception of big ET-1, all the peptides used in this study induced an initial transient depressor response (-32 +/- 3 mmHg, n = 18). Although BQ-123 (1 mg kg-1, i.v., bolus) did not affect the absolute magnitude of the fall in MAP, the ETA receptor antagonist significantly prolonged the depressor responses induced by ET-3 and SX6b. 5. Thus, BQ-123 attenuates the pressor, but not the depressor effects of ET-1, big ET-1, ET-3, SX6b and SX6c. Complete inhibition of the pressor responses could not be achieved, suggesting that a component of the pressor response is not mediated via the ETA receptor. PMID- 8448604 TI - Calcium pyrophosphate dihydrate crystal deposition disease. PMID- 8448605 TI - Manipulative treatment of the spine. PMID- 8448606 TI - Pyrophosphate arthropathy: a prospective study. AB - One hundred and four consecutive patients with pyrophosphate arthropathy were followed prospectively and re-studied at a mean of 4.6 years. Sixty-four patients (43F, 21M; mean age at review 71.2 years) completed the study (24 died of unrelated disease, 16 were unavailable for review). The knee had been the major presenting joint in 91%. Symptoms were improved in 41%, unchanged in 33% and had worsened in only 27%: 27% developed symptoms in new joints. Radiographic changes of arthropathy were unaltered in 50%: although 'worsening' of previously involved joints was seen in 16%, the most common change was increase in osteophyte with bone remodelling (31%). Despite dynamic changes in chondrocalcinosis in most patients (77%) there was no correlation between extent of calcification and progression of arthropathy. It is concluded that the outcome of pyrophosphate arthropathy is not necessarily progressive, patients presenting with acute attacks alone do particularly well. PMID- 8448607 TI - Does hypothyroidism increase the prevalence of chondrocalcinosis? AB - To investigate whether or not there is an association between hypothyroidism (HPT) and chondrocalcinosis (CC) 100 HPT patients and 100 controls matched for the age and sex were evaluated prospectively. All the patients were examined clinically, and X-rays of knees, wrists and pelvis, and biological evaluation of thyroid hormones, calcium, uric acid, iron and alkaline phosphatase levels were recorded. X-rays were assessed independently by two radiologists blind to the thyroid status of the patient. The prevalence of CC was 17% in the HPT patients and 10% in the controls (NS). No correlation was found between CC duration and mechanism or treatment of HPT. We suggest that HPT and CC are two diseases that may co-exist in patients but without any causal or mechanistic relationship. PMID- 8448608 TI - Autoantibody to the nuclear antigen RA33: a marker for early rheumatoid arthritis. AB - Sera from 47 patients with early (< 3 months) arthritis of any type were investigated for anti-RA33, a new anti-nuclear autoantibody characteristic of RA, and the diagnoses determined within the following 8-14 months. In addition, seven patients with unclassified arthritis of > 4 months duration, who were all anti RA33 positive, were followed for up to 2 years to establish their final rheumatologic diagnoses. Four of 47 early arthritis patients' sera were anti-RA33 positive at the initial evaluation; 14 of these 47 patients (30%) could be classified as RA (according to established criteria) at the final evaluation. All four anti-RA33 positive patients belonged to the RA group (27% of RA patients); of the 33 non-RA patients none had anti-RA33 (P = 0.005). Rheumatoid factor was found in four RA (none of whom had anti-RA33), but also in two non-RA patients (P = 0.05). Finally, the study involved seven additional patients with longer standing, initially unclassified, anti-RA33 positive arthritis: in all of them a diagnosis of RA could be established within 3 years of disease onset. These results suggest that anti-RA33 helps to discriminate early RA from other forms of early arthritis and, in the absence of an established diagnoses, it is predictive of RA. Its discriminative capacity appears to be better than and complementary to that of RF. PMID- 8448609 TI - The relationship of haemoglobin to serum erythropoietin concentrations in the anaemia of rheumatoid arthritis: the effect of oral prednisolone. AB - Previous studies of the erythropoietin response to anaemia in RA have yielded conflicting findings. Some have found the response to be impaired and others have found a normal response. We have compared erythropoietin (EPO) levels measured by radioimmunoassay, in 54 anaemic rheumatoid patients and 55 patients with iron deficiency anaemia but no inflammatory disease. The erythropoietin response in the rheumatoid patients was impaired compared with the control group (P < 0.025) but only seven rheumatoid patients showed a response which fell below the 95% confidence intervals predicted for the control group. Rheumatoid patients who fell within the highest quartile for serum ferritin concentrations (i.e. those most likely to have anaemia of chronic disease) had significantly lower EPO levels compared with the control group (P < 0.01). EPO levels in rheumatoid patients within the lowest quartile for ferritin (i.e. those with iron deficiency anaemia) were not significantly different from the control group (P = 0.670). The difference in EPO response between the RA patients in the upper and lower quartile for ferritin approached but did not achieve significance (P = 0.056). In a second study 15 anaemic RA patients were given a 5-day course of oral prednisolone 1.5 mgkg-1. Hemoglobin did not rise significantly until day 4 but EPO levels fell by day 1 (P < 0.005) and remained lower than pretreatment values throughout the study. Thus, in RA patients, anaemia of chronic disease is associated with inappropriately low EPO concentrations but this does not appear to be the major cause of the anaemia and Hb response to prednisolone does not depend upon an increase in EPO concentration. PMID- 8448610 TI - Extra-articular manifestations are uncommon in southern Chinese with rheumatoid arthritis. AB - Rheumatoid arthritis is characterized by both articular and extra-articular manifestations. Few studies have addressed the prevalence of extra-articular manifestations in non-Caucasoid races. We have studied 153 Southern Chinese patients with RA and found that such features are uncommon when compared with previous reports in Caucasoids. The only extra-articular manifestations were rheumatoid nodules which were present in 4.6%, and episcleritis and cutaneous vasculitis in 0.7% each. A further 12.4% had mild sicca symptoms. These findings were in direct contrast with the severity of articular disease as 73% of patients had erosive disease which was graded as severe in 37%. The reason for the low prevalence of extra-articular manifestations is not known but may be due, in part, to the rarity of the HLA-DR4 subtype, HLA-Dw4 in the Southern Chinese population. PMID- 8448611 TI - Elevated resting heart rate in rheumatoid arthritis: possible role of physical deconditioning. AB - Thirty-four patients with RA, 76 diabetic subjects (DM) and 67 healthy controls (CR) were studied in order to study cardiovascular autonomic function in RA. Valsalva manoeuvre, deep breathing test and active orthostatic test were used. Resting heart rate (resting HR) was markedly elevated in the RA and DM groups. Therefore, the groups were compared using analysis of variance with age and resting HR as covariates. The analyses showed no differences in cardiovascular responses between the RA group and CR group but cardiovascular responses were significantly diminished in the DM group compared with both the CR group and RA group. Our data indicate that the parasympathetic efferent pathway mediating cardiovascular reflexes via the nervus vagus is intact in RA. Thus elevated resting HR in RA does not seem to be due to peripheral parasympathetic damage. Physical deconditioning may explain the elevation of resting HR in patients with RA. PMID- 8448612 TI - A clinical and radiological study of back pain in rheumatoid arthritis. AB - Five hundred and three patients with RA were questioned about the symptom of back pain. Chronic back pain, lasting more than 3 months, occurred in 33 per cent of the group. A group of 100 back pain patients were studied in more detail using a structured questionnaire, clinical examination and radiology. Ninety-four of these patients had low back pain. Particular clinical patterns (such as that of the facet syndrome) were sought but no clear characteristics were found. Fifty two lumbar spine X-rays were available from the RA population and these were compared to 52 age and sex matched X-rays from outpatients with chronic mechanical low back pain. Significant differences between these groups radiologically were a higher frequency of osteoporosis and a higher frequency of disc narrowing without associated osteophytes in the RA population. This study differs from previous reports which found other characteristic radiological features of RA of the lumbar spine (spondylolisthesis, facet erosions, and vertebral fracture), a discrepancy possibly resulting from the use of a control group having low back pain. PMID- 8448613 TI - Contraceptive practice in women with systemic lupus erythematosus. AB - Since there are few data on the use of various birth control methods in systemic lupus erythematosus (SLE), we performed a cross-sectional study of the actual contraceptive practices in a group of 85 Finnish female SLE patients of reproductive age. We also recorded side-effects experienced during the use of oral contraceptives (OCs) and intrauterine devices (IUDs). The use of contraception was lower in SLE patients than in healthy women of the same age (59 vs 77%, P < 0.001). Sexually active SLE patients requiring contraception used more often barrier and natural methods (P < 0.001) and less often OCs (P < 0.05) than the corresponding healthy women. The risk of deep venous thrombosis in SLE patients while using oestrogen-containing OCs was slightly increased (RR 2.3, 95% CI 0.5 to 10.3). Twenty-five (78%) of the 32 patients, who had used progestagen only contraceptives discontinued them because of side effects, which were mainly gynaecological. Major bleeding or pelvic infection did not occur during the use of IUDs. PMID- 8448614 TI - The diagnostic value of salivary gland scintigraphy in patients suspected of primary Sjogren's syndrome. AB - The diagnostic value of salivary gland scintigraphy in patients suspected of having primary Sjogren's syndrome (SS) was studied in 149 consecutive patients who presented with joint and/or muscle complaints in combination with dryness of the mouth and/or eyes and in 20 control subjects. The diagnosis primary SS could be established in 26 of these patients. Salivary gland scintigraphy scored by means of analogue pictures was abnormal in 19 out of 26 patients with primary SS but abnormal scintigrams were also found in 57 of the 123 patients without primary SS and in five of the controls. This resulted in a positive predictive value of an abnormal salivary gland scintigram of 25% and a negative predictive value of a normal investigation of 90%. From the high number of false positive test results in the patient population studied it is concluded that salivary gland scintigraphy has only a limited discriminatory value for the diagnosis of primary SS. PMID- 8448615 TI - Rheumatoid arthritis patients coping without drug therapy. AB - In view of the variable and unpredictable efficacy and toxicity of non-steroidal anti-inflammatory and disease-modifying anti-rheumatic drugs, it is not surprising that some patients with rheumatoid arthritis elect to cope without recourse to these medications. We describe four of these patients, consider the lessons to be learnt, and identify further research that needs to be done on this aspect of illness behaviour. PMID- 8448616 TI - Smoking, a cause of back trouble? AB - Epidemiological studies strongly imply that smoking may be a risk factor for back problems. It has been speculated that this is due to frequent coughing, unhealthy life style or osteoporosis in smokers. All of these hypotheses, however, do not accord with the experimental evidence. A new theory is therefore proposed. It suggests that smoking leads to malnutrition of the disc which in turn renders it more vulnerable to mechanical stress. Malnutrition can be brought about by carboxyhaemoglobin formation, nicotine-induced vasoconstriction, arteriosclerotic vessel wall changes, impairment of fibrinolytic activity and changes in the flow properties of blood. The evidence supporting these pathomechanisms is discussed. Future studies should test the above hypothesis experimentally. PMID- 8448617 TI - Osteoarthritis in weight-bearing wrists? AB - To test the suggestion [1] that turning the wrist into a weight-bearing joint by using a stick is likely to cause OA in that joint, 50 consecutive patients (excluding those with RA) who had used a stick for more than 1 year were studied clinically and radiographically. The data did not support this hypothesis. The changes in the original paper, as in one of these patients, were likely to be due to avascular necrosis. PMID- 8448618 TI - Pseudogout provoked by pregnancy. AB - Four women with chondrocalcinosis are described. Each developed acute attacks of synovitis during pregnancy (confirmed pseudogout, two; presumptive pseudogout, two). All patients had recognized predisposing factors (metabolic, familial, traumatic) for premature calcium pyrophosphate deposition, and in three this was their first episode of synovitis. This first report of provocation of pseudogout by pregnancy is of interest in respect of putative mechanisms of crystal shedding. PMID- 8448619 TI - Calcium pyrophosphate deposition disease--involvement of the acromioclavicular joint with pseudocyst formation. PMID- 8448620 TI - Systemic lupus erythematosus-like syndrome with focal proliferative glomerulonephritis during D-penicillamine therapy. AB - We report a patient with RA who developed serological evidence for lupus disease in the presence of a crescentic immune complex glomerulonephritis (GN). This occurred after 4 years therapy with penicillamine and resolved on withdrawal of this drug and following treatment with cyclophosphamide. PMID- 8448621 TI - Polyautoimmunity in a young woman. AB - A young woman with the HLA phenotype A1, A2, B5, B8, DR3, DR4 developed RA, idiopathic thrombocytopenic purpura (ITP), pernicious anaemia (PA), Hashimoto's thyroiditis (HT), systemic sclerosis (SS), pancreatic exocrine insufficiency (PEI) and coeliac disease (CD) before dying from vasculitic complications. A family study revealed RA, PA and insulin-dependent diabetes mellitus (IDDM) amongst her first degree relatives. Her case emphasizes the clinical and immunogenetic links between the autoimmune diseases. PMID- 8448622 TI - Rhabdomyolysis with markedly elevated serum creatine kinase following injury to the tongue. PMID- 8448623 TI - Expression of the 65 kD heat shock protein in human chondrocytes. PMID- 8448624 TI - Aluminium-related bone disease presenting with calcaneal stress fractures. PMID- 8448625 TI - Oligoarthritis--a presenting feature of occult coeliac disease. PMID- 8448626 TI - Salmonella antibodies in healthy populations in Finland and the UK--how many Salmonella-triggered reactive arthritides are there? PMID- 8448627 TI - Injection therapy of superficial rheumatoid nodules. PMID- 8448628 TI - Bronchiectasis and rheumatoid arthritis: potential pitfalls in interpretation. PMID- 8448629 TI - An international consensus report: the use of cyclosporin A in rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is a painful and disabling condition that is becoming increasingly widely recognized as associated with early mortality. Since the late 1970s, clinical trials have been conducted in both Europe and North America in order to determine whether oral cyclosporin A (CyA) has a role in the management of RA and, if so, how it might best be used. That experience, plus recent advances in our understanding of the mechanisms of action of CyA and of the pathology of RA, provides the foundation for the following consensus recommendations. It is assumed that physicians experienced both in the management of refractory RA and in the use of CyA will be treating patients outside experimental research protocols. All patients will be informed of the potential risks and benefits of treatment with CyA. Any patient to be started on CyA will have a documented complete past medical history, present history and physical examination. PMID- 8448630 TI - The Use of Cyclosporin A in Rheumatoid Arthritis. Proceedings of an International Consensus Meeting. Buckinghamshire, United Kingdom, 19-20 July, 1992. PMID- 8448631 TI - Cytokines and anti-cytokines. AB - The cause of RA is unknown but there are several hypotheses: an autoimmune mechanism; a superantigen-driven disease; an infection with an unusual pathogen (e.g. lentivirus); and a non-specific infectious stimulus acting on a particular genetic background. Whatever the cause(s) of RA, it would appear that cytokines are very important mediators of the pathology. Genetic polymorphisms with Mendelian inheritance have been characterized in regulatory regions of cytokines such as IL-1, TNF and related genes. It is possible, therefore, that whatever the initiating stimulus might be, the possession of different cytokine alleles may confer greater or lesser risk of developing a progressive disease. PMID- 8448632 TI - Monotherapy in rheumatoid arthritis. AB - In the past few years there has been considerable debate regarding the optimal therapy for patients with RA. The arguments have been phrased in a variety of ways and frequently involve the concept of therapy with multiple drugs. The underlying assumption is that current therapy is inadequate and that the whole therapeutic approach to RA needs rethinking. The evidence on which these assumptions are made is reviewed here. Additionally, this paper argues for a more discriminating approach using prognostic indicators to identify the minority of patients with persistent unresponsive disease (and poor outcome) for whom more aggressive therapy should be reserved. PMID- 8448633 TI - Approaches to the management of rheumatoid arthritis: rationale for early combination therapy. AB - In evaluating current therapy of RA, it is becoming recognized that sequential single drug treatment, as exemplified by the traditional therapeutic pyramid, is often too little and too late in patients with aggressive 'at risk' synovitis. Evidence exists that prevention of joint damage correlates best with control of clinical and laboratory measures of inflammation, regardless of the medication used. Until a major breakthrough occurs in this disease, it is recommended that patients with 'at risk' RA be treated aggressively to achieve early control of inflammation, and then 'bridge down' to a simplified maintenance programme. While currently available fast and slow acting drugs might be used in combination today for early induction therapy, newer drugs, cancer chemotherapeutic preparations, biologic agents, or novel therapies may prove more effective and superior tomorrow. Control trials will be necessary to establish the most effective and least toxic induction and maintenance programmes. PMID- 8448634 TI - The 'side effects' of rheumatoid arthritis: joint destruction, disability and early mortality. AB - Most patients with RA experience disease progression over periods longer than 5 years, characterized by radiographic joint destruction, declines in functional capacity to perform activities of daily living, frequent work disability, high levels of co-morbidities, and death earlier than expected. These long-term consequences of RA may be viewed as 'side effects' of disease, which must be balanced against possible side effects of drugs in planning treatments of patients with RA. Aggressive approaches, which may include acceptance of mild and even moderate side effects of drugs, may be appropriate in efforts to prevent 'side effects' of RA. PMID- 8448635 TI - Immunological actions of cyclosporin A in rheumatoid arthritis. AB - Rheumatoid arthritis is present in a population which is heterogeneous both clinically and immunologically. A variety of cells including lymphocytes, macrophages and fibroblasts play important roles in its pathogenesis, but the T cell appears to be a common thread throughout the disease process. Treatments aimed at reducing these lymphocytes mechanically and specifically result in a good clinical response in many patients. The mechanism of action of cyclosporin A (CyA) in inhibiting T lymphocytes presents a more specific form of therapy. Though limited, studies including immune profiling suggest that certain subgroups of RA patients are more likely to respond to CyA. Further studies are required to test these findings, but targetted therapy with CyA could result in enhanced and longer-lasting efficacy. PMID- 8448636 TI - The immunopathogenesis of rheumatoid arthritis. PMID- 8448638 TI - The optimal use of cyclosporin A in rheumatoid arthritis: efficacy and outcome measures including quality of life. AB - The debate as to which outcome measures are appropriate in clinical trials involving RA has been in progress for some time. A recent critique (Felson DT et al. Arthritis Rheum 1990;33:140-9) addressed some of the problems that have been raised and suggested solutions. Shortcomings noted included multiple measures, lack of standardization and insensitive measures. This paper discusses those and other areas of concern in the light of the findings of consensus meetings that have taken place recently and which suggest that agreement is within reach. PMID- 8448637 TI - The effects of cyclosporin A on bone and cartilage. AB - Cyclosporin A (CyA) is a potent immunomodulatory agent with an increasing number of clinical applications. Although its precise mechanisms of action are yet to be elucidated, one of the most important known properties of CyA is its ability to inhibit the production of cytokines involved in the regulation of T cell activation. There is also evidence for direct effects on other cell types, such as B cells, macrophages, and bone and cartilage cells. The effects of CyA on T cells and on bone, cartilage and synovial cells, which can produce a range of cytokines, are of interest in the study of inflammatory diseases such as RA. It has been shown, for example, that in vitro CyA inhibits bone resorption induced by interleukin-1, 1,25-dihydroxy-vitamin D3, parathyroid hormone and prostaglandin E2. In vivo, it protects against adjuvant arthritis. PMID- 8448639 TI - Cyclosporin A in rheumatoid arthritis: overview of efficacy. AB - Five clinical trials of cyclosporin A (CyA) in the treatment of RA were reviewed and an initial evaluation made of clinical endpoints across the studies. A composite effect score for efficacy and the rates of dropout due to toxicity were each compared to earlier meta-analyses evaluating the relative efficacy and toxicity of second-line drugs for RA. The overall percentage improvements over a 6-month assessment period for the various clinical endpoints were all found to meet a minimal clinical improvement of 20%: tender joints, 20%; grip strength, 22%; swollen joints, 29%; functional index, 29%; morning stiffness, 40%; and CRP, 45%. The exception was ESR (16%). The composite effect for CyA indicated significant improvement over placebo (P < 0.001). This effect in excess of placebo was in the range of that found for antimalarial drugs. The toxicity associated with CyA was similar to that found with drugs with low toxicity, such as auranofin. A more detailed analysis using individual patient data and the results of two studies is planned. PMID- 8448640 TI - Efficacy of cyclosporin A in rheumatoid arthritis: worldwide experience. AB - The effects of cyclosporin A (CyA) on the activity of RA have mainly been investigated in patients with active, refractory, long-term disease. The data obtained in these trials suggest that CyA is not only a symptomatic treatment for RA but can also be considered a DMARD. The potential benefits of CyA on one hand and its potential toxicity on the other indicate that a careful assessment should be made of its use in patients with early active RA. PMID- 8448641 TI - Cyclosporin A nephropathy in patients with rheumatoid arthritis. AB - Patients with RA are at risk of cyclosporin A (CyA) toxicity as they have an increased incidence of underlying renal pathology and because of the probable co administration of NSAIDs. CyA dose, blood levels, and changes in serum creatinine are linked to the severity of renal biopsy changes in patients with RA and other autoimmune disorders, but only limited data regarding the safety of long-term CyA therapy have been reported. Low-dose CyA (preferably without NSAID co administration) should be reserved for those patients with a poor prognosis who can be carefully monitored using a combination of renal function studies, CyA blood levels and renal biopsy assessment. Consideration should be given to the development of a management strategy that includes renal biopsy at defined intervals in order to detect the onset of progressive renal damage, and which could potentially allow eligible patients to benefit from long-term CyA therapy. PMID- 8448642 TI - Renal morphology after cyclosporin A therapy in rheumatoid arthritis patients. International Kidney Biopsy Registry of Cyclosporin (Sandimmun) in Autoimmune Diseases. AB - Because cyclosporin A (CyA) has the potential of causing structural damage to renal tissue, kidney biopsies from 41 patients with RA treated with CyA at a maximum dose of 4.6 +/- 1.2mg/kg/day (mean +/- SD) for 16 +/- 7 months, were compared to kidney biopsies from 11 RA patients not treated with CyA and 41 sex- and age-matched control subjects without RA (kidney donors). Four patients in the CyA group but none in the control groups had morphological features of CyA nephropathy, defined as at least moderate focal interstitial fibrosis with tubular atrophy, arteriolar alterations or both. The dose of CyA and the initial serum creatinine level, but not treatment duration, were higher in patients with CyA nephropathy than in those without it. None of the 24 patients whose CyA dose did not exceed 5 mg/kg/day and whose serum creatinine did not rise by 50% or more above his or her pre-CyA level developed CyA nephropathy. These results indicate that the therapeutic conditions which have been shown to minimize the risk of CyA nephropathy in other autoimmune diseases can also prevent its occurrence in RA, and that CyA nephropathy can be avoided when the following rules are observed: the initial dose should be 2 or 3 mg/kg/day; the maximum dosage should not exceed 5 mg/kg/day; serum creatinine should be monitored regularly for as long as CyA is administered, and the dose should be decreased each time creatinine rises by more than 30% above the pre-CyA level. PMID- 8448643 TI - Malignancies in rheumatoid arthritis patients treated with cyclosporin A. AB - More than a thousand RA patients have been treated with cyclosporin A (CyA) in clinical trials. In seventeen of them, tumours developed after treatment with the drug. An indirect approach used to calculate the relative risk associated with the use of CyA in clinical trials suggested that: (i) RA itself increases the risk of cancer development; (ii) the use of CyA further increases the risk by approximately the same degree as DMARDs; and (iii) neither the pattern of malignancies nor the risk associated with CyA seems to be different from that observed with conventional DMARDs. Nevertheless, patients treated with CyA should be carefully monitored while more experience is gathered. PMID- 8448644 TI - Cyclosporin A in rheumatoid arthritis--future perspectives. AB - The new programme for the use of cyclosporin A (CyA) in RA is based on the hypothesis that the drug is more efficacious and better tolerated in early RA and that it can be used as part of therapy with a rational combination of drugs. This paper gives some examples of the ongoing and planned studies that have been set up to test that hypothesis. The development of CyA therapy of RA is a stepwise process. The next steps depend on the outcome of current trials and also on our ability to identify progressive RA at a very early stage. PMID- 8448645 TI - The organization of the microtubule associated protein tau in Alzheimer paired helical filaments. AB - The structural relationship of the microtubule associated protein tau to paired helical filaments (PHF) was examined by high resolution transmission electron microscopy (TEM) without treatment with any chemical fixatives. Neurofibrillary tangles (NFT) were isolated in the absence of detergent from Alzheimer diseased brains, were freeze-dried, and were vertically platinum-carbon replicated for TEM. The PHF we observed made one helical turn (L) in 74 +/- 8.5 nm and had a wide region (W) of 14.8 +/- 0.6 nm similar to PHF previously modeled with a periodic morphology. The PHF thin region (T) measured approximately 2.4 nm, approximately 4.9 nm, approximately 7.4 nm and approximately 9.7 nm and the most often observed width was approximately 2.4 nm. No surface features regularly divide the PHF into two filaments. Morphologically the PHF are thin helical ribbons with an often observed thickness of approximately 2.4 nm. At high magnification, approximately 1.0 nm and some approximately 0.4 nm strands identical to normal and denatured tau monomer covered PHF surfaces and were aggregated in non-periodic fashion. Bovine tau polymer approximately 2.1 nm diameter filaments, trapped on a filter, were partially heat denatured and showed some of the morphological features of PHF. PMID- 8448646 TI - Variation in firing order of human soleus motoneurons during voluntary and reflex activation. AB - The activation of motoneurons in a muscle pool is said to proceed as an ordered array in response to both dorsal root stimulation and voluntary activation, with small motoneurons being recruited before larger ones. We have examined 19 voluntarily recruited soleus motor units in 5 normal subjects and found that in 18 cases, the lowest threshold motor unit recruited by slowly increasing 'tonic' voluntary activity was different from the lowest threshold unit recruited by electrical stimulation of the tibial nerve in the popliteal fossa (phasic Hoffman reflex). The initially recruited voluntary units were, however, part of the pool influenced by the stimulated afferents because, during tonic activation, the timing of their discharge could be shown to be altered by electrical stimulation at a lower intensity than that required for H recruitment at rest. These findings suggest that the pool of soleus motoneurons responding to the voluntary command "tonically plantar flex your ankle" differs somewhat, in order of activation, from the pool responding to phasic stimulation of the largest diameter fibers in the tibial nerve, perhaps because of inhomogeneities in the distribution of descending or segmental inputs to the soleus motoneuron pool. Whether this partitioning is functional or a reflection of minor, random variations in synaptic density remains to be determined. PMID- 8448647 TI - Acrylamide-induced depletion of microtubule-associated proteins (MAP1 and MAP2) in the rat extrapyramidal system. AB - Acrylamide, an occupational neurotoxicant, reduced MAP1 and MAP2 distribution in different regions of rat brain. Different components of the extrapyramidal system (caudate-putamen, globus pallidus, substantia nigra and red nucleus) revealed differential distribution of MAP1 and MAP2 in acrylamide-treated animals. Rats were treated with acrylamide (estimated mean dose: 15 mg/kg/day) for 2 weeks and MAP1 and MAP2 were localized according to Sternberger's peroxidase-anti peroxidase technique. MAP1 labelled neuronal perikarya and dendrites almost with a similar intensity, but MAP2 immunostaining was more intense in dendrites than neuronal perikarya. Acrylamide caused a near-total loss of MAP1 and MAP2 immunoreactivity in caudate-putamen. Other components of the extrapyramidal system were relatively less affected by acrylamide. These results indicate that caudate-putamen is more susceptible to the action of acrylamide than other components of the extrapyramidal system studied. The depletion of MAP1 and MAP2 immunoreactivity by acrylamide appears to be an early biochemical event preceding peripheral neuropathy. The loss of MAPs immunoreactivity occurs first in dendrites and proceeds toward the perikarya. This study indicates that acrylamide not only causes axonal damage but may also induce dendritic degeneration. PMID- 8448648 TI - Dopamine D1 and D2 receptors in the caudate nucleus of spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. AB - A series of studies was carried out to characterize the binding properties of dopamine D1 and D2 receptors in membrane homogenates of the caudate nucleus of spontaneously hypertensive rats (SHR). Binding in SHR was studied at the age of 4 weeks when the rats were still in the prehypertensive phase, and at the age of 8 weeks, during the phase in which blood pressure is increasing dramatically; age matched normotensive Wistar-Kyoto rats (WKY) were used as controls. Binding to dopamine D1 receptors was studied using [3H]SCH 23390. Antagonist binding of dopamine D2 receptors was performed with [3H]spiperone. At both ages no differences were found between SHR and WKY in affinity (Kd) or concentration (Bmax) of dopamine D1 and D2 receptors. Binding to the high affinity state of the dopamine D2 receptor was measured using the agonist [3H]N-n-propylnorapomorphine (NPA). No differences in Bmax or Kd were found between SHR and WKY at both ages studied, indicating that the ratio between dopamine D2 receptors in the high and in the low affinity state is not altered in spontaneous hypertension. Although the results do not reveal differences in affinities or concentrations of dopamine D1 or D2 receptors in the caudate nucleus between SHR and WKY, a role in the development of hypertension for the here described lack of receptor up-regulation in connection with our previous observation of lower release of dopamine in the caudate nucleus of SHR, cannot be excluded. PMID- 8448649 TI - Antagonism of the non-opioid component of ethanol-induced analgesia by the NMDA receptor antagonist MK-801. AB - Recent evidence from our laboratory suggests that the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (dizocilpine) selectively antagonizes non-opioid (i.e. naloxone-insensitive) mechanisms of stress-induced analgesia in mice. For example, we have recently demonstrated that a low dose of MK-801 (0.075 mg/kg, i.p.) antagonizes the non-opioid component of a mixed opioid/non-opioid swim stress-induced analgesia (SSIA) resulting from forced swimming for 3 min in 20 degrees C water. Since ethanol-induced analgesia (EIA) has been found to be only partially attenuated by naloxone, we hypothesized that MK-801 would similarly block the non-opioid component of EIA. The effects of MK-801 and of the opioid receptor antagonist naloxone (10 mg/kg, i.p.) on analgesia produced by ethanol (2.5 g/kg in 20% vol/vol, i.p.) were studied in control mice and in mice selectively bred for high (HA) or low (LA) SSIA. HA mice showed significantly more, and LA mice significantly less, EIA than controls. Naloxone and MK-801 significantly attenuated EIA in control and HA mice, and in these lines the combined administration of both antagonists blocked EIA completely. In LA mice, which displayed very little EIA, naloxone but not MK-801 reversed EIA completely. These findings provide additional evidence for the role of the NMDA receptor in non-opioid mechanisms of analgesia. The finding that mice selectively bred for high and low SSIA, also display high and low EIA suggests common mediation of the effects of stress and ethanol on antinociceptive processes. PMID- 8448650 TI - Time course of anatomical regeneration of descending brainstem neurons and behavioral recovery in spinal-transected lamprey. AB - In larval lamprey 4 weeks after a spinal transection locomotor patterns were usually complete along the body in whole animals. In in vitro preparations locomotor activity was restricted to a few millimeters below the transection. Retrograde labeling indicated that descending axons from a few brainstem neurons had grown through the transection site and probably directly activate the rostral spinal locomotor networks, but no direct descending projections were found to the caudal spinal cord. Thirty-two weeks after spinal transection locomotor activity was recorded at long distances below the transection in both whole animals and in vitro preparations. The number of brainstem neurons projecting to the rostral spinal cord below the transection appeared near normal while there was a reduced but significant projection to the caudal spinal cord. Thus, at long recovery times it appears that regenerated descending axons can directly activate the motor networks in both the rostral and caudal spinal cord and initiate locomotor activity, as is the case in normal animals. PMID- 8448651 TI - No triazolam-induced expression of Fos protein in raphe nuclei of the male Syrian hamster. AB - While the visual projections to the suprachiasmatic nuclei (SCN) play a role in mediating the effects of light on circadian rhythms, the functional significance of the serotonergic projection from the raphe nuclei (RN) to the SCN is uncertain. Because previous results indicated that RN would appear to be a likely site for triazolam (Tz)-induced phase shifts, we used the expression of Fos protein as a marker of Tz-induced neuronal activation. Immunocytochemistry was used to visualize the presence of Fos-like protein. Tz-induced Fos-labeled nuclei were found in superior colliculi, Edinger-Westphal nuclei (EW) and dorsal tegmental nuclei (DTg), but not in the RN. The SCN showed only occasionally labeled nuclei in all experimental groups, whereas there was no Tz-induced Fos immunoreactivity in the intergeniculate leaflet (IGL). The present data not necessarily exclude the implication of the RN in the phase shifting effect of Tz. The phase shift could still be accomplished using a different set of immediate early genes (IEG), or without an IEG response. Alternatively, as will be discussed, other pathways could mediate the phase shifting effect of Tz. PMID- 8448652 TI - Low-threshold motor effects produced by stimulation of the facial area of the fifth somatosensory cortex in the cat. AB - The motor effective sites of the fifth somatosensory cortex (SV) in the cat were mapped in detail by using unit recording and intracortical microstimulation (ICMS) techniques. The motor effective sites for facial muscle contraction were identified using stimulus currents of less than 30 microA. Of the 257 effective sites detected, 49% were activated by stimulus currents of less than 20 microA and of these, 51% responded to stimulus currents of less than 10 microA. ICMS within the facial area of the SV neuron produced contralateral eye-blinking, the lowest threshold current for which was 2 microA and ICMS within the SV neurons produced whisker movements, the minimum threshold current for which was 4 microA. Furthermore, stimulation of some SV neurons at a threshold current as low as 4 microA produced whisker movements and some responded to both visual and cutaneous stimuli. Ablation of areas 6a beta, 3a, SII, SIII and the motor cortex did not eliminate or reduce the low-threshold responses elicited by this weak stimulation of the SV. These motor effective areas receive input from the contralateral cutaneous of the surrounding muscle motor effective region. Our results suggest that the described effect is independent of motor effective areas. PMID- 8448653 TI - Insulin reduces norepinephrine transporter mRNA in vivo in rat locus coeruleus. AB - Acute and chronic in vitro insulin treatment can inhibit the uptake of norepinephrine (NE) by adult rat brain synaptosomes and slices, fetal neuronal cultures, and PC12 cells. In the present study we tested whether chronic in vivo insulin treatment could alter the biosynthetic capacity of rat locus coeruleus neurons for the NE transporter protein (NET). Chronic third ventricular insulin treatment resulted in a suppression of NET mRNA to about one third of the level of vehicle-treated controls. Our finding suggests that insulin may play a regulatory role in the synthesis of this transporter, thereby modulating activity in CNS noradrenergic pathways. PMID- 8448654 TI - Higher and longer stress-induced increase in dopamine concentrations in the nucleus accumbens of animals predisposed to amphetamine self-administration. A microdialysis study. AB - Individual vulnerability to the reinforcing effects of drugs appears to be a crucial factor in the development of addiction in humans. In the rat, individuals at risk for psychostimulant self-administration (SA) may be identified from their locomotor reactivity to a stress situation such as exposure to a novel environment. Animals with high locomotor responses to novelty (high responders, HR) acquire amphetamine SA, while animals with low responses (low responders, LR) do not. In this study we examined by microdialysis whether stress-induced extracellular dopamine (DA) concentrations in the nucleus accumbens differed between these two groups of animals. This neurotransmitter was studied because it is thought to be involved in the reinforcing effects of psychostimulants. Furthermore, previous studies have shown that HR animals have a higher basal DOPAC/DA ratio in the nucleus accumbens and higher extracellular concentrations of dopamine in this structure in response to cocaine. The stress procedure used in this experiment consisted of a 10 min tail-pinch. HR animals displayed a higher and longer stress-induced changes in DA concentrations than the LR group. Regression analysis showed that stress-induced changes in DA levels accounted for 75% of the variance observed in the locomotor response to a novel environment. Since higher DA activity in the nucleus accumbens has been reported in animals in which the propensity to psychostimulant SA is induced by brain lesions or life events, this biochemical modification may be one neurobiological substrate of the predisposition to acquire psychostimulant self-administration. PMID- 8448655 TI - Comparison of the effects of elevated intracellular aluminum and calcium levels on neuronal survival and tau immunoreactivity. AB - Both calcium and aluminum have been implicated in the cell damage and death that occurs in several neurodegenerative disorders including Alzheimer's disease (AD). We examined the effects of experimentally elevated intraneuronal levels of aluminum ([Al]i) and/or calcium ([Ca2+]i) on neuronal degeneration and antigenic alterations in the microtubule-associated protein tau in cell cultures of rat hippocampus and human cerebral cortex. Exposure of cultures to Al3+ alone (200 microM) for up to 6 d did not result in neuronal degeneration. Neurons exposed to the divalent cation ionophore A23187 degenerated within 4 h when Ca2+ was present in the culture medium whether or not Al3+ was present. Measurements of [Ca2+]i using the calcium indicator dye fura-2 demonstrated a direct relationship between increased [Ca2+]i and neuronal degeneration. In contrast, neurons did not degenerate when exposed to A23187 in the presence of Al3+ and the absence of Ca2+, despite a 10-fold elevation in [Al]i as measured by laser microprobe mass spectrometry. Calcium influx, but not aluminum influx, elicited antigenic changes in tau similar to those seen in AD neurofibrillary tangles. Neurons exposed to glutamate in the presence of Al3+ but in the absence of Ca2+ were not vulnerable to injury. Finally, increased [Al]i occurred in neurons that degenerated as the result of exposure to glutamate indicating that aluminum associates with degenerating neurons. Taken together these data indicate that, in contrast to increased [Ca2+]i, elevated [Al]i may not induce degeneration or antigenic changes in tau. PMID- 8448656 TI - Effects of tonic vibration reflex on motor unit recruitment in human wrist extensor muscles. AB - Tonic vibration reflex was used to investigate the effects of muscle spindle Ia afferent activation on motor unit (MU) recruitment in human wrist extensor muscles. The MU force recruitment threshold recorded in the extensor carpi radialis muscles were quantitatively compared under two experimental situations: (1) during tonic isometric reflex contractions induced by mechanical tendon vibration and during voluntary contractions performed at the same velocity; (2) during two voluntary imposed ramp contractions (0.25 N.s-1) performed the one immediately before, and the other immediately after a tonic vibration reflex. In the first situation, it was observed that the Ia afferents activated by tendon vibration exerted a strong homonymous facilitatory action on their bearing muscles (extensor carpi radialis longus and brevis), while their heteronymous action on the synergistic muscle (extensor carpi ulnaris) was very weak. The MU recruitment thresholds in the extensor carpi radialis muscles were therefore significantly lower during the tonic reflex contraction than during the voluntary contraction. In the second situation, the tonic vibration reflex induced a facilitatory after-effect which decreased the MU recruitment thresholds during the subsequent voluntary imposed ramp contraction. It is suggested that this post vibratory effect may have been due either to a postsynaptic potentiation of the motoneurones or to a reflex sensitization of the muscle spindles increasing their response to voluntary isometric contraction and consequently, increasing their facilitatory reflex action on the motoneurone pool. PMID- 8448657 TI - Effect of ascorbate on Na(+)-independent and Na(+)-dependent uptake of [3H]norepinephrine by rat primary astrocyte cultures from neonatal rat cerebral cortex. AB - We have previously reported that primary astrocyte cultures prepared from neonatal rat brains show Na(+)-dependent, tricyclic antidepressant-sensitive, high-affinity uptake of [3H]norepinephrine ([3H]NE). Other workers, however, using primary astrocyte cultures from neonatal mice, have failed to find such uptake. This prompted us to examine possible reasons for the variability of the uptake in primary astrocyte cultures such as growth conditions and the effect of ascorbic acid. The presence of ascorbic acid increased the Na(+)-dependent uptake of NE by inhibiting the Na(+)-independent component. Na(+)-dependent uptake in rat cultures occurs when either fetal bovine or horse serum are present in the growth media, but not in a serum-free growth medium. Other workers have shown a species difference such that, even under optimal uptake conditions where rat astrocyte cultures exhibit Na(+)-dependent [3H]NE uptake, mouse astrocyte cultures do not. PMID- 8448658 TI - Excitation induced by acetylcholine after injection of Limulus ventral photoreceptor with ml muscarinic receptor mRNA. AB - We investigated whether a human neurotransmitter receptor for acetylcholine (Ach) could couple Ach to light-sensitive pathways in Limulus photoreceptors. Two to three days after injection of human ml muscarinic mRNA into Limulus ventral photoreceptors the cells depolarized in response to Ach. PMID- 8448659 TI - The expression of B-50/GAP-43 in Schwann cells is upregulated in degenerating peripheral nerve stumps following nerve injury. AB - We have detected mRNA for B-50 (GAP-43, pp46, F1, neuromodulin), which was originally believed to be a neuron-specific protein, in non-neuronal cells in the rat sciatic nerve. In control rats, the level of B-50 mRNA in sciatic nerve tissue was much lower than in dorsal root ganglia. Following nerve crush or transection, the expression of B-50 mRNA in the distal nerve stump increased dramatically between 1 and 2 days post-injury. The B-50 mRNA levels in the distal stump of crushed nerves remained elevated for up to 4 weeks and subsequently returned to control levels after 7 weeks. In contrast, after nerve transection B 50 mRNA levels in the distal nerve portion continued to increase up to 7 weeks post-lesion. No changes in the levels of the B-50 transcript were observed in the proximal portion of either crush-lesioned or transected sciatic nerves. In situ hybridization demonstrated B-50 mRNA associated with Schwann cells in the distal nerve stump. The observation that Schwann cells are capable of producing B-50 mRNA was confirmed by Northern blot analysis of total RNA isolated from primary Schwann cell cultures. Taken together, these data show the expression of B-50 mRNA by Schwann cells and the up-regulation of B-50 mRNA in reactive Schwann cells upon loss of axonal contact. PMID- 8448660 TI - Evidence for the existence of cAMP-dependent protein kinase phosphorylation system associated with specific phosphoproteins in stable microtubules from rat cerebral cortex. AB - Cyclic AMP is a second messenger by which different extracellular signals are transduced into biological responses. Within the cell, most of the effects of cAMP are mediated through the cAMP protein kinase which appears to be localized in specific compartments of the cell near to their substrate proteins. In the present study, we have investigated the possible association of cAMP-dependent protein kinase, its substrate proteins and RII binding proteins in stable microtubules from rat cerebral cortex. The results show that in this fraction there is a cAMP binding protein of 52-54 kDa. This cAMP receptor is in the inactive holoenzyme form, since the addition of cAMP (5 microM) induces an increase in the endogenous phosphorylation of different stable microtubules polypeptides, which is completely inhibited in the presence of a specific protein kinase inhibitor (PKI 5-24 1 microM). Interestingly, overlay binding assay reveals that beside MAP2, 32P/R II is able to bind stable microtubule proteins of M(r) 150 and 75 kDa which, according to their electrophoretic mobility, can also be endogenous substrates for the enzyme. We conclude that cAMP-dependent phosphorylation system is indeed associated with stable microtubules from rat cerebral cortex. PMID- 8448661 TI - Corticosterone impairs hippocampal neuronal calcium regulation--possible mediating mechanisms. AB - Corticosterone (CORT), the predominant glucocorticoid of rats which is secreted during stress, increases hippocampal neuronal vulnerability to excitotoxins, hypoxia-ischemia, and hypoglycemia in an energy-dependent manner. A mechanism for this endangerment could be the CORT-induced impairment of hippocampal neuronal calcium regulation. We have shown that CORT causes an energy-dependent prolonged elevation of cytosolic free calcium ([Ca2+]i) in response to kainic acid stimulation in cultured hippocampal neurons. That study utilized the calcium sensitive dye fluo-3, which is unsuitable for determination of basal [Ca2+]i. The present study circumvents that limitation by using the dye fura-2 AM. We have replicated the previous demonstration that CORT potentiates the [Ca2+]i response to KA; we have also observed that CORT elevates basal [Ca2+]i concentrations. Furthermore, we have observed that the mechanism for this CORT impairment of calcium regulation involves a reduction in stimulus-induced calcium efflux. Energy-dependent disruptions in neuronal calcium regulation, such as induced by CORT, have been associated with subsequent neurotoxicity. Thus, the CORT-induced impairment of hippocampal neuronal calcium regulation could be the mechanism for the neuronal vulnerability and toxicity evident following CORT treatment and stress. PMID- 8448662 TI - Radioligand binding to the N-methyl-D-aspartate receptor/ionophore complex: alterations by ethanol in vitro and by chronic in vivo ethanol ingestion. AB - The effects of ethanol on the binding of [3H]MK-801, [3H]L-glutamate, [3H]glycine and [3H]CGS 19755 to the N-methyl-D-aspartate receptor were determined in membranes from mouse cortex and hippocampus. Under equilibrium conditions, ethanol in vitro (100 mM) did not alter the apparent affinity or binding site density for any of these ligands. However, in the presence of glutamate and the selective glycine antagonist, 5,7-dichlorokynurenic acid, ethanol inhibited the non-equilibrium binding of [3H]MK-801. This inhibition could be reversed in a time- and concentration-dependent manner by addition of glycine. These data suggest that ethanol may inhibit N-methyl-D-aspartate receptor-mediated responses by altering the kinetics of channel activation. Chronic in vivo ethanol ingestion by mice, that resulted in tolerance to and physical dependence on ethanol, produced an increased density of hippocampal [3H]MK-801 and [3H]L-glutamate binding sites, but not [3H]glycine or [3H]CGS 19755 binding sites. It is possible that chronic ethanol ingestion may influence the subunit composition of the NMDA receptor complex. PMID- 8448663 TI - Spreading depression induces c-fos-like immunoreactivity and NGF mRNA in the rat cerebral cortex. AB - Application of potassium chloride (KCl) to the brain surface elicits spreading depression which leads to a marked induction of the proto-oncogene c-fos in the treated cerebral cortex at the earliest time examined (90 min). High levels of c fos immunoreactivity are observed up to 6 h after KCl treatment. The areas affected include the cingulate, entorhinal and frontoparietal cortex throughout the treated hemisphere. The c-fos expression preceded an increase in both NGFmRNA and NGF-like protein(s). A maximal increase in c-fos was detected within 3 h, whereas NGFmRNA peaked at 12 h and NGF-like protein(s) reached their maximum level 24 h after KCl application. The most prominent increase in NGFmRNA was measured in the entorhinal cortex (50-fold), but other cortical areas also showed a moderate increase of 2-3-fold. In conclusion, our results provide evidence that increases in c-fos and NGF expression are early adaptive responses following brain injury. PMID- 8448664 TI - Hormone-sensitive periods for the control of motoneuron number and soma size in the dorsolateral nucleus of the rat spinal cord. AB - The dorsolateral nucleus (DLN) of the rat lumbosacral spinal cord is sexually dimorphic, with males having more and larger DLN motoneurons than do females. The development of this dimorphism depends on the presence of perinatal androgens. The present study sought to determine the periods in development during which the DLN is sensitive to the masculinizing effects of the androgen testosterone propionate (TP). The size and number of DLN motoneurons in neonatally ovariectomized female rats that were exposed to TP during either the late prenatal, early postnatal, or late postnatal period were compared to control males and females. Both late prenatal and early postnatal TP injections significantly increased DLN number by 48% and 50%, respectively, but the sensitive period for TP masculinization of soma size seems to be primarily postnatal, because prenatal TP injections had little or no effect on that measure. The sensitive period for TP masculinization of DLN neuron number is similar to that of the sexually dimorphic spinal nucleus of the bulbocavernosus (SNB). However, the sensitive period for TP masculinization of DLN soma size appears to begin later than for the SNB. PMID- 8448665 TI - Regulation of melatonin-sensitivity and firing-rate rhythms of hamster suprachiasmatic nucleus neurons: constant light effects. AB - Rhythms of spontaneous firing rate and of responsiveness to pressure ejection of melatonin were recorded from neurons in the Syrian hamster suprachiasmatic nuclei (SCN) in a slice preparation. In animals taken from light-dark cycles (LD 14:10), SCN cells had high firing rates during the projected day and lower rates during the projected night. The proportion of melatonin-suppressed cells (35% overall) was also high during the day and fell during the night, while melatonin activated approximately 23% of cells at all phases. To assess the source of the melatonin responsiveness rhythm, hamsters were exposed for approximately 48 h to constant illumination (LL) to suppress melatonin secretion. LL exposure before slice preparation altered both firing-rate and melatonin-responsiveness rhythms. Firing rates failed to show a morning peak and remained at low levels, with no indication of daily rhythmicity. Melatonin responsiveness also failed to show the usual rhythm and even tended to rise at night. Overall melatonin responsiveness rose after LL exposure so that 50% of cells were suppressed and 21% activated. LL exposure also increased the proportions of cells which showed regular baseline firing rates. Control studies indicated that pressure artifacts did not account for either suppression or activation by melatonin, while the composition of the saline vehicle appeared to be responsible for the activations recorded. The results indicate that brief LL exposure alters SCN sensitivity to melatonin and SCN rhythmicity in Syrian hamsters, perhaps as a result of the loss of the daily melatonin secretion rhythm. Physiological melatonin patterns may have important effects on the rodent circadian pacemaker. PMID- 8448666 TI - Regulation of melatonin-sensitivity and firing-rate rhythms of hamster suprachiasmatic nucleus neurons: pinealectomy effects. AB - As a test of the origin of the melatonin-sensitivity rhythm recorded from SCN cells in brain slices from intact Syrian hamsters, hamsters were either pinealectomized to remove the influence of endogenous melatonin, or sham operated. Cells from sham-operated hamsters showed a trough in responsiveness during the projected night. Pinealectomy eliminated the daily rhythm of melatonin responsiveness, reduced the proportions of cells responding to melatonin, and raised response thresholds in those cells that did not meet the criterion for responsiveness. Pinealectomy also altered the firing-rate rhythm so that the morning peak in firing rate was not sustained and the nocturnal trough was attenuated, leading to a firing-rate rhythm with reduced amplitude compared to those recorded from sham-operated or intact animals. These results indicate a role for endogenous melatonin in regulating both melatonin sensitivity and the integrity of the SCN firing-rate rhythm, and they suggest why pinealectomy can disrupt circadian organization in some situations. PMID- 8448667 TI - Morphine alters the firing of cold-receptive neurons in the superficial dorsal horn of the medulla in the rat. AB - Effects of morphine (1-3 mg/kg, i.v.) were tested on the innocuous cold-receptive input in the superficial dorsal horn of the medulla. The static activity of most cold-receptive (cold-specific) neurons (12/16) was reduced, whereas an enhancement (4/16) was observed in the remaining neurons. Naloxone (200 micrograms/kg, i.v.) reversed, partially or completely, the effects of morphine in 9/12 cold-receptive neurons, and enhanced the static activity of some cold receptive neurons. Static activity, at different adapting temperatures, during a warming (10 degrees C-->40 degrees C) and a cooling (40 degrees C-->10 degrees C) sequence at steps of 5 degrees C was reduced by morphine. The effects of morphine were also tested on the static as well as the dynamic responses of 9 cold receptive neurons. The effects of morphine on the dynamic responses were not dependent on the static firing frequency. Morphine produced similar effects, excitatory or inhibitory, on the static as well as the dynamic responses of 7/9 neurons whether the static firing frequency was high (17-33 Hz) or low (< 12 Hz). However, morphine effects on static and dynamic responses were different in the remaining 2 neurons (high static firing frequency). We suggest that the predominantly inhibitory effect of morphine on the innocuous cold receptive input in the medullary dorsal horn may explain the inhibitory effect on the perception of cooling stimuli by systemic morphine in behavioral studies. PMID- 8448668 TI - Effects of chronic total sleep deprivation on central noradrenergic receptors in rat brain. AB - The effect of chronic total sleep deprivation (TSD) on the regulation of central noradrenergic receptors was evaluated. Rats were subjected to 10 days of TSD by the disk-over-water method. As in previous TSD studies, these rats showed greater increases in food intake and energy expenditure and greater eventual declines in waking body temperature than their yoked-control (TSC) rats. After sacrifice, alpha 1-, alpha 2-, and beta-adrenoceptors were determined in 11 brain regions using radioligand binding assays with [3H]prazosin, [3H]rauwolscine, and 125I iodocyanopindolol, respectively. Adrenoceptor density and affinity values were significantly different among TSD, TSC, and normally caged control rat groups only for the cerebellum, which showed higher alpha 2-binding density concomitant with lower affinity and lower beta-binding density than cage control rats. Such changes are attributable to apparatus or stimulus effects common to TSD and TSC rats. Given the absence of firm evidence for a TSD-induced downregulation of central noradrenergic receptors, the present results offer no support for the hypothesis of Siegel and Rogawski that a major function of paradoxical sleep is to upregulate these receptors. PMID- 8448669 TI - Multiple brain systems generating the rat auditory evoked potential. I. Characterization of the auditory cortex response. AB - The objectives of this study were to characterize the auditory cortex response in the rat and to examine its contributions to the auditory evoked potentials (AEPs) recorded from the dorsal and lateral skull. This was accomplished by simultaneously recording AEPs from the cortical surface and from skull screw electrodes in anesthetized animals. The initial positive-negative response (P17 N32) was largely restricted to the cortical region corresponding to area 41. More detailed examination of the AEP mapping revealed multiple subcomponents (P9, P14, P17, P19) underlying the initial positivity, with differing topographies. Stimulus-response properties further dissociated the multiple positive subcomponents. Reversible local neurochemical suppression confirmed the auditory cortical origin of these AEPs. The auditory cortex-generated AEPs were refractory to barbiturate anesthesia which eliminated all dorsal skull AEPs, indicating that primary auditory cortical AEPs do not make a significant contribution to the dorsal skull-recorded ('vertex') AEPs. The findings raise issues regarding multiple parallel auditory processing systems and their associated AEPs. PMID- 8448671 TI - Temperature changes associated with forebrain ischemia in the gerbil. AB - Changes in brain temperature during and following ischemia have not been systematically examined in the gerbil. In this study, gerbils were subjected to a 5-min bilateral carotid artery occlusion. During surgery, skull and body temperatures were maintained with a heated water blanket and a homeothermic blanket unit, respectively. Rectal, skull and brain temperatures were monitored throughout ischemia and for up to 3 h in the post-ischemic period. Intra-ischemic brain temperature fell by approximately 1.5 degrees C even though skull and rectal temperatures remained at normal values. Since brain temperature modulates the extent of ischemic injury it may not be sufficient to rely on skull and/or rectal temperature readings, especially during periods of anesthesia. PMID- 8448670 TI - Multiple brain systems generating the rat auditory evoked potential. II. Dissociation of auditory cortex and non-lemniscal generator systems. AB - This study addressed the issue of multiple parallel auditory processing systems and their relationship to the skull-recorded auditory evoked potentials (AEPs) in the unanesthetized, unrestrained rat. In the preceding paper (Brain Res., 602 (1993) 240-250) it has been shown that auditory cortex activity does not contribute significantly to the vertex maximal AEPs recorded from the dorsal skull of the rat. In the present study, mapping of the AEP skull distribution revealed two sets of components: one set maximal at the dorsal skull vertex, and another set at the lateral skull), but not the early (P7-P11, N15) lateral skull components generated in auditory cortex. Bilateral auditory cortex ablation eliminated the lateral skull maximal AEP components, but not the dorsal skull maximal components. These findings support extensive parallel processing of auditory inputs (reflected by the dorsal AEPs) in the absence of primary auditory cortex. Ablation of primary auditory cortex did result in a modulation of the dorsal skull AEPs, indicative of an interaction between the geniculocortical system and the parallel system which generates the dorsal AEPs. PMID- 8448672 TI - Proliferation of microglia/macrophages in the demyelinating CNS and PNS of twitcher mouse. AB - In demyelinating lesions in the central and peripheral nervous systems of twitcher mouse, a murine model of globoid cell leukodystrophy, marked increases of [3H]thymidine-labeled elements including Mac-1 immunopositive (Mac-1+) microglia/macrophages was observed. Their proliferative activities were already pronounced at the postnatal day (P) 20, an early stage of demyelination, peaked at P30 and then declined at P45, at the terminal stage of the disease. Many of the [3H]thymidine-labeled Mac-1+ cells had morphological features of ramified microglia. Macrophage-like Mac-1+ cells were less frequently labeled. The results of this study showed that (1) microglia/macrophages proliferated in the genetic demyelinating lesions, (2) many dividing Mac-1+ cells had the shape of ramified microglia and (3) the rate of proliferation declined in later stages when reactive microglia/macrophages were abundant in the lesions. The temporal events of this study suggest that signal(s) from the degenerating myelin or myelin forming cells stimulate(s) cellular proliferation and that ramified microglia were one of the principal-dividing elements in the lesion. The biological mechanisms underlying the decline of the proliferative activity of microglia require further studies. PMID- 8448673 TI - Intravitreal injections of neurotrophic factors support the survival of axotomized retinal ganglion cells in adult rats in vivo. AB - After transection of the optic nerve (ON) in adult rats, retinal ganglion cells (RGC) progressively degenerate until, after two months, a residual population of only about 5% of these cells survives. In this study, we investigated the effect of regeneration-associated factors from sciatic nerve (ScN), BDNF, and CNTF on the survival of adult rat RGC after intraorbital ON transection. Neurotrophic factors were injected into the vitreous body. Rats were allowed to survive 3, 5, or 7 weeks, and the remaining viable RGC were then labelled by retrograde staining with the carbocyanine dye, 4Di-10Asp, which was applied onto the proximal nerve stump in vivo. The animals were sacrificed 3 days later and RGC counted in retinal whole mounts. Due to progressive degeneration following nerve transection the number of surviving RGC decreased to about 10% of the initially labelled population after 3 weeks, to about 8% after 5 weeks, and to about 5% after 7 weeks. Survival of axotomized cells could be prolonged using either of the neurotrophic factors: after 3 weeks a 2-3-fold increase in the number of viable RGC could be obtained compared to uninjected controls and to those which received injection of buffer. The prolonged survival effect vanished after 5 and 7 weeks, and no additive effect could be seen when combining brain-derived neurotrophic factor (BDNF) and ciliary neuronotrophic factor (CNTF) treatment. Morphometric analysis of labelled cells revealed that all neurotrophic factors supported predominantly large RGC with somal areas > 250 micron 2. In retinae from rats that survived the ON transection for several months, a characteristic population of axotomy-resistant RGC remained alive. Their few, very large, and often curled dendrites showed signs of placticity in the depleted inner nuclear layer of the adult rat retina. We conclude that the intraocular injection of CNTF, BDNF, and ScN-derived medium, which retard the process of lesion-induced RGC degeneration, may be successfully used as a subsidiary strategy in transplatation protocols. This would result in larger populations of RGC which can be recruited to regenerate their axons and provide a basis for functional recovery. PMID- 8448674 TI - Collateral projections of single neurons in the nucleus raphe magnus to both the sensory trigeminal nuclei and spinal cord in the rat. AB - After injecting Diamidino yellow and Fast blue respectively into the sensory trigeminal nuclei and spinal cord, we observed doubly labeled cells in the nucleus raphe magnus (NRM). Combining the fluorescent retrograde double labeling with serotonin (5-HT) immunofluorescence histochemistry, we further found that about 30% of the doubly labeled NRM neurons showed 5-HT-like immunoreactivity (5 HT-LI). Such 5-HT-LI NRM neurons may modulate nociceptive activities simultaneously in the sensory trigeminal nuclei and spinal cord by sending axon collaterals to these regions. PMID- 8448675 TI - Chromogranin A, a soluble synaptic vesicle protein, is found in cortical neurons other than previously defined peptidergic neurons in the human neocortex. AB - Neuropeptides in the cerebral cortex have previously been identified in non pyramidal neurons only. By comparing the location of chromogranin A (CgA), a soluble protein of large dense-core synaptic vesicles, with that of SMI-32, neuropeptide Y (NPY), parvalbumin (PV) and calbindin (CaBP) using double label immunohistochemistry, we demonstrate that CgA is present in pyramidal neurons as well as in several subtypes of non-pyramidal neurons. PMID- 8448676 TI - Transient hyperemia succeeds oligemia in the wake of cortical spreading depression. AB - Regional cerebral blood flow (rCBF) was examined following single episodes of cortical spreading depression (CSD) in rat brain after an intravenous bolus injection of [14C]iodoantipyrine. Cortical rCBF decreased to approximately 75% of control values during the first 60 min after CSD. This change was succeeded at 90 105 min by a small, transient flow increase. rCBF returned to normal at 120 min after CSD, and remained normal for the following 2 h. The same sequence of rCBF changes has been recorded in patients during migraine attacks. This study therefore supports the notion that CSD may serve as an animal model of migraine. PMID- 8448677 TI - Recruitment of motor units in human flexor carpi ulnaris. AB - In 1949, Denny-Brown reported that the motoneuron pool of the human flexor carpi ulnaris (FCU) muscle was fractionated into subpopulations, each subpopulation being activated during a different voluntary motor task. The following report presents data on motor unit recruitment in the human FCU muscle for the tasks of isometric flexion and ulnar deviation, cocontraction of the forearm muscles and non-isometric flexion of the wrist. These observations show that every FCU motor unit tested reliably, contributed to all four tasks, that is, no separate subpopulations were observed for any of the contractions tested. Furthermore, the order of recruitment was the same for all four tasks. PMID- 8448678 TI - Sensitization to Chortoglyphus arcuatus and Aleuroglyphus ovatus in Dermatophagoides spp. allergic individuals. AB - The prevalence of specific IgE to the storage mites Aleuroglyphus ovatus (Ao) and Chortoglyphus arcuatus (Ca) was studied in 77 individuals with allergic asthma and/or chronic allergic rhinitis. All these individuals had a positive skin test (weal > or = 3 mm) to extracts of Dermatophagoides pteronyssinus (Dp) and/or Dermatophagoides farinae (Df). Sera from 29 non-atopic individuals were used as controls. A RAST was considered positive when a serum bound > or = 1% of the total counts added. The prevalence of a positive RAST to Dp was 75.3%, and to at least one of the two storage mites (Ao and Ca), 76.6%. Among patients with a positive RAST to Dp, 79.3% and 75.8% were RAST positive to Ao and Ca, respectively. RAST inhibition studies with a pool of sera from 13 subjects with high RAST binding to all three mites showed significant crossreactivity between Ao and Ca and minimal to moderate crossreactivity between Dp and Ao and Ca. This study demonstrates that sensitization to Ao and Ca is common in individuals with respiratory allergies in Cartagena, Colombia and suggests that Ao, Ca and Dp have unique and common allergenic determinants. PMID- 8448679 TI - Natural history of cows' milk allergy in children: immunological outcome over 2 years. AB - In this investigation 98 children (median age 24 months) with cows' milk allergy (CMA) were studied over a median period of 2 years to see whether acquisition of clinical tolerance to cows' milk was associated with the changes in levels of IgG and IgE anti-cows' milk antibodies, and skin test reactivity to a cows' milk extract. Two groups of CMA patients were examined. The first were IgE sensitized and responded rapidly to small volumes of cows' milk with urticaria, and/or exacerbations of eczema, and/or wheeze, and/or vomiting (n = 69). The second, a late reacting group (n = 29) demonstrated coughing, diarrhoea, eczematoid rashes, and/or a combination of these which developed more than 20 hr after commencing normal volumes of cows' milk. Significant immunological changes were confined to the 69 IgE sensitized immediate-reacting-group of patients. Of these, there were 15 children who achieved clinical tolerance to cows' milk and they showed a significant fall in the levels of skin test reactivity to cows' milk over the study period (P < 0.01). In addition, these 15 children had lower serum IgE antibodies to cows' milk proteins both at the outset and the final follow-up compared with the 54 patients whose CMA persisted. No consistent change in the IgG antibody responses to cows' milk proteins was seen in either group of patients over the study period. The findings suggest patients with immediate type hypersensitivity to cows' milk proteins whose disease persists for more than 2 years have a more severe dysregulation of IgE synthesis to cows' milk proteins from the outset.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448680 TI - Histamine content, synthesis and degradation in human nasal mucosa. AB - Histamine content and enzyme activities of histamine metabolism, histidine decarboxylase (HDC), histamine N-methyltransferase (HMT) and histaminase (diamine oxidase, DAO) in human nasal mucosa were determined with a highly sensitive and specific fluorescent method which was combined with high performance liquid chromatography. Histamine content and HDC activity were determined in 10 specimens of nasal polyp, nine specimens of maxillary sinus and five specimens of inferior turbinate. HMT and histaminase activities were determined in 15 specimens of nasal polyp, nine specimens of maxillary sinus and five specimens of inferior turbinate obtained during surgical therapy. Histamine and activities of HDC, HMT and histaminase were detected in all specimens except the case of histaminase activity in one specimen of nasal polyp. The mean values of histamine content and activities of HDC, HMT and histaminase of human nasal mucosa were 137.3 nmol/g wet weight, 26.3 fmol/min/mg protein, 26.4 pmol/min/mg protein and 0.5 pmol/min/mg protein, respectively. Histamine content in the mucosal tissue of the maxillary sinuses was significantly higher than that of nasal polyps or inferior turbinates. There were no significant differences in HDC activities among three kinds of nasal mucosa. Activities of HMT and histaminase, including their kinetic constants (Km and Vmax values for histamine) indicated that HMT has a greater potential than histaminase for histamine degradation in the human nasal mucosa. The presence of these enzymes suggests that these activities constitute an important modulating factor in histamine mediated allergic and inflammatory reactions in human nasal mucosa. PMID- 8448681 TI - Peripheral blood mononuclear cells from house dust mite allergic patients produce IL-2 in response to specific allergen challenge. AB - Proliferative responses and production of IL-2 by peripheral blood mononuclear cells of patients with Dermatophagoides pteronyssinus rhinitis +/- asthma were measured at up to 24 hr intervals from 1-8 days, after stimulation with mitogen (PHA), antigen (SKSD) and specific allergen (D. pteronyssinus). IL-2 was measured in culture supernatants using the murine CTLL cell line bioassay. Compared to non atopic controls, patients had significantly higher proliferative responses to D. pteronyssinus and SKSD but similar responses to PHA. In patients, maximal proliferative responses to PHA, SKSD and D. pteronyssinus were at 3, 6 and 7 days, respectively. IL-2 levels in response to stimulation with D. pteronyssinus were significantly higher in patients than controls, where only background levels were found (15.4, 7.9-30.7 x 10(-2) U/ml [mean, range] n = 11; vs 2.2, 0.1-8.4 x 10(-2) U/ml, n = 6; P < 0.05). In contrast, IL-2 production to PHA and SKSD, although higher in patients, was not significantly different than controls. These results suggest allergic patients possess a population of T cells expandable by specific allergen which are induced to secrete IL-2. PMID- 8448682 TI - Atopic dermatitis: correlation of peripheral blood T cell activation, eosinophilia and serum factors with clinical severity. AB - In the first part of this study peripheral blood lymphocyte subpopulations, their activation state and various serum parameters were measured in extrinsic and intrinsic atopic dermatitis (AD) patients compared to normal individuals. Beside the characteristic eosinophilia, significantly increased numbers of CD4+ T cells with increased expression of IL-2 receptors (IL-2R) and HLA-DR were noted in the AD patients. In addition, extrinsic AD patients showed increased numbers of CD23+ B cells and decreased numbers of CD16+ natural killer cells. Moreover, increased serum levels of eosinophil cationic protein (ECP) and soluble IL-2R as well as soluble factors that prolong survival of eosinophils in vitro could be demonstrated. In the second section of this study we determine how these blood immunological parameters relate to the clinical severity of the skin lesions of AD, by weekly analysis of 12 AD patients attending a high altitude clinic for 3 to 6 weeks. The patients were divided into two groups on the basis of treatment with topical steroids, but during the observation period a significant improvement in clinical status was observed in all AD patients independent of topical steroid therapy. A progressive decrease in eosinophil and activated T cell numbers, soluble IL-2R levels and serum eosinophil survival prolonging activity could be demonstrated, which closely correlated with the clinical severity of the AD. PMID- 8448683 TI - Sequence similarity between a major allergen from the dermatophyte Trichophyton tonsurans and exo 1,3-beta-glucanase. PMID- 8448684 TI - International Consensus Report on Diagnosis and Management of Asthma. PMID- 8448685 TI - Cows' milk allergy. PMID- 8448686 TI - The role of air pollution in asthma. AB - Laboratory studies have clearly shown that inhalation of SO2 by asthmatics can cause a significant degree of wheezing at concentrations considerably lower than those which affect non-asthmatics. Concentrations as low as 0.2 p.p.m. have a significant effect, especially in subjects who are mouth breathing or undergoing heavy exercise. The effects of SO2 appear to be short-lived and not increased by more prolonged exposure (10 min versus 1 hr). WHO air quality guidelines on levels of SO2 have been based to a large extent on these studies and are set at or just below the reported threshold for effects on at risk groups. Thus the 1 hr recommended maximum is 0.16 p.p.m. (350 micrograms/m3). These guidelines have been exceeded in the U.K. on many occasions in the recent past [2] suggesting that asthmatics are at risk in high pollution areas from SO2 induced exacerbations of their asthma. This is particularly true considering that virtually all the laboratory studies have been performed on mild asthmatics. The effects on moderate and severe asthmatics, or those with marked lability of their asthma, could conceivably be seen at much lower concentrations of SO2. Similarly O3 can cause impairment in lung function at concentrations frequently detected in ambient air in the U.K. in both asthmatics and non-asthmatics with no evidence of an increased effect on asthmatics. This appears to be a restrictive rather than an obstructive defect. Ozone can also cause an increase in airways responsiveness to both non-specific bronchoconstrictors such as histamine and specific allergen. Both these effects are likely to be due to the pro-inflammatory effects of ozone and as such could be implicated both in exacerbating asthma through increased airway responsiveness and causing asthma through triggering an inflammatory reaction in the airways. No study has addressed the important question as to whether the incidence of bronchial hyperresponsiveness is increased in areas of high ozone pollution. The results with NO2 in the laboratory are equivocal. On balance the evidence suggests that any effect on asthmatics is likely to be small. Similarly while inhalation studies with acid aerosols have demonstrated some impairment in lung function in asthmatics the changes have been small and of brief duration. Laboratory studies while raising the level of suspicion and allowing dose response curves to be calculated cannot accurately mimic the effects of real air pollution with its combination of interacting circumstances and effects of prolonged exposure.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8448687 TI - The involvement of eosinophils in the patch test reaction to aeroallergens in atopic dermatitis: its relevance for the pathogenesis of atopic dermatitis. AB - Atopic dermatitis (AD) is considered a T-cell mediated disease. Activated T cells, mainly of the CD4-subtype, are abundantly present in lesional AD skin. Although not many intact eosinophils are present, deposits of eosinophil derived major-basic-protein (MBP) and eosinophil-cationic-protein (ECP) suggest eosinophil involvement. After patch testing AD patients with aeroallergens, an eczematous reaction develops after 24-48 hr at the site of application. This patch test reaction shows macroscopic resemblance to lesional AD skin and does not take place in normal individuals, asthma and allergic rhinitis patients. Lymphocytes together with eosinophils infiltrate into the dermis 2-6 hr after allergen application. Twenty-four to forty-eight hours after patch testing, eosinophils are in an activated state since they release ECP (being EG2 positive). At this point in time eosinophils have also infiltrated the epidermis. Here they are EG2-negative. Forty-eight to seventy-two hours after patch testing the eczematous reaction decreases. This coincides with disappearance of eosinophils from both the dermis and the epidermis; then, a dendritic staining pattern can be observed in the epidermis with anti-eosinophil peroxidase. Thus, eosinophils infiltrate the dermis and epidermis after patch testing AD patients with aeroallergens and release part of their granular constituents. Recent in vitro investigations revealed that eosinophils from the circulation of AD patients react more powerfully in in vitro test systems such as chemiluminescence, chemotaxis and endothelial adherence and transmigration. It is very likely that this activated (= primed) state is caused by the influence of lymphocyte-derived cytokines like IL-3, IL-5 and GM-CSF, since activated lymphocytes in the circulation (and tissue) may release these cytokines. The primed state of the eosinophils may facilitate tissue infiltration. The subsequent activation of eosinophils within the tissue leading to mediator release and the function of these mediators need to be further elucidated. The close similarity between the cellular events after a patch test reaction to aeroallergens in AD patients and those present in lesional AD skin suggests that the patch test reaction may be a helpful in vivo model to study the pathogenesis of AD. The prominent involvement of lymphocytes and eosinophils in this reaction also suggests some similarity with late phase reactions (LPR) observed in the skin after intracutaneous allergen challenge. PMID- 8448688 TI - Ontario's birthing-centre concept may have impact on hospitals, MDs. PMID- 8448689 TI - Canadian aid program in Angola faces huge problems. PMID- 8448690 TI - A case for smaller bombs. PMID- 8448691 TI - Recovery from this addiction was sweet indeed. PMID- 8448692 TI - Failure to attack quackery draws fire in UK. PMID- 8448693 TI - The physician-patient relationship and the ethic of care. PMID- 8448694 TI - Canadian National Breast Screening Study. PMID- 8448695 TI - Canadian National Breast Screening Study. PMID- 8448696 TI - Canadian National Breast Screening Study. PMID- 8448697 TI - Canadian National Breast Screening Study. PMID- 8448698 TI - Canadian National Breast Screening Study. PMID- 8448699 TI - Tobacco tax revenue and smokers' health care costs. PMID- 8448700 TI - Plight of the homeless. PMID- 8448702 TI - Medicine without soul? PMID- 8448701 TI - Timing of the Medical Council of Canada clinical examination. PMID- 8448703 TI - Assessing assessment: evaluating geriatric technology. PMID- 8448704 TI - Clinical practice guidelines as legal norms. PMID- 8448705 TI - Guidelines for the adoption of new technologies: a prescription for uncontrolled growth in expenditures and how to avoid the problem. AB - The guidelines proposed by Laupacis and associates do not stem from economic theory and are a prescription for uncontrolled growth in health care expenditure. In particular, cost-effectiveness ratios provide information relevant to allocation decisions only in very special circumstances that do not usually apply in practice. When two interventions are compared a positive cost-effectiveness ratio (the common case) can tell us, at best, what additional costs will be incurred to generate the additional outcomes. From an economic perspective the information required to determine the attractiveness of a new technology is different: the source of the additional resource requirements must be identified and the opportunity cost of their redeployment estimated. Because the cost effectiveness ratio (cost/-QALY) is sensitive to the method chosen to calculate QALYs, guidelines that do not specify (or justify) the appropriate method for calculating outcomes are unlikely to produce comparable results (or common yardsticks). In a health care system such as Canada's in which there is always pressure to introduce more effective technology, even if it is more costly, there is a risk of using such noncomparable data to justify adoption of particular technologies. The method of technology evaluation proposed by us is consistent with the stated goal of maximizing the community's health-related well-being for a given level of resources allocated to health care and ensures that new technologies are adopted only if this adoption represents an improvement in resource allocation. PMID- 8448706 TI - Technology assessment and cost-effectiveness analysis: misguided guidelines? PMID- 8448707 TI - Tentative guidelines for using clinical and economic evaluations revisited. PMID- 8448708 TI - Assessing the effectiveness of geriatric services: a proposed methodology. Canadian Task Force on the Periodic Health Examination. AB - This article presents an explicit and systematic methodology, adapted from the practices of the Canadian Task Force on the Periodic Health Examination, for assessing the effectiveness of geriatric services in managing specific diseases and disabilities. The five steps in the process are as follows: (1) the identification of target diseases and disabilities, (2) the development of a specific service model for each target condition, (3) the establishment of criteria that must be satisfied for service procedures to be considered effective, (4) a review of the evidence from published clinical research to determine whether service procedures meet the criteria and (5) the classification of recommendations based on the strength of the evidence. These methods can enhance scientific standards for assessing effectiveness by encouraging a systematic, comprehensive and objective evaluation of the evidence. PMID- 8448709 TI - [How effective is the teaching of critical analysis of scientific publications? Review of studies and their methodological quality]. AB - OBJECTIVE: To evaluate studies assessing the effectiveness of teaching critical appraisal of the literature to medical students. DATA SOURCES: French and English articles published between 1980 and 1990 indexed on MEDLINE or FAMLI as well as articles identified from the bibliographies. STUDY SELECTION: Studies were evaluated if the subjects were undergraduate or postgraduate medical students and if the teaching intervention was aimed at improving one or more of the following areas: knowledge in clinical epidemiology and biostatistics, reading habits and ability to critically appraise a scientific article. DATA EXTRACTION: The methodologic quality of the articles was assessed by three evaluators, who used a modified version of Poynard's checklist to assign a score. Articles with a score of 60% or more were considered satisfactory. The reliability of the checklist was evaluated by means of the kappa (kappa) coefficient and a coefficient of intraclass correlation. DATA SYNTHESIS: For the three evaluators the mean kappa coefficient was 0.33 and the coefficient of intraclass correlation 0.70. Five of the 10 studies had an overall score of 60% or higher. The quality of the individual sections of the articles varied: purpose of the study 85%, description of the population 58%, methods 44%, analysis of results 50%, and conclusions 90%. CONCLUSIONS: The effectiveness of teaching critical appraisal of the literature remains uncertain. More rigorous methods are needed in research in this area. PMID- 8448710 TI - James Bovell: a remarkable 19th-century Canadian physician and the forgotten mentor of William Osler. PMID- 8448712 TI - Is vegetarianism a diet or an ideology? PMID- 8448711 TI - Computed tomography before lumbar puncture in acute meningitis: a review of the risks and benefits. AB - OBJECTIVE: To determine the indications, if any, for routine computed tomography (CT) of the brain before lumbar puncture in the management of acute meningitis. DATA SOURCES: Original research papers, reviews and editorials published in English from 1965 to 1991 were retrieved from MEDLINE. The bibliographies of these articles and of numerous standard texts were examined for pertinent references. A survey of local neurologists was conducted, and legal opinion was sought from the Canadian Medical Protective Association. DATA EXTRACTION: There were no studies directly assessing the risks of lumbar puncture in meningitis; however, all sources were culled for other pertinent information. RESULTS: No cases could be found of patients with acute meningitis deteriorating as a result of lumbar puncture. The neurologic consensus refuted the need for CT in typical acute meningitis. All sources stressed speedy lumbar puncture and the early institution of appropriate antibiotic therapy to minimize the severity of the illness and the risk of death. CONCLUSIONS: (a) There is no evidence to recommend CT of the brain before lumbar puncture in acute meningitis unless the patient shows atypical features, (b) for patients with papilledema the risks associated with lumbar puncture are 10 to 20 times lower than the risks associated with acute bacterial meningitis alone, (c) CT may be necessary if there is no prompt response to therapy for meningitis or if complications are suspected, (d) the inability to visualize the optic fundi because of cataracts or senile miosis is not an indication for CT and (e) there are no Canadian legal precedents suggesting liability if physicians fail to perform CT in cases of meningitis. PMID- 8448713 TI - [Panic attacks and panic disorders in the child]. AB - Panic disorders in adults have been the object of many studies. They are better known in adolescents but have been noticed insufficiently in children although panic disorder is potentially dangerous at that age. After demographic considerations, the clinical aspects are examined and illustrated using two detailed observations. PMID- 8448715 TI - Psychiatric consultation in the eastern Canadian Arctic: I. Development and evolution of the Baffin Psychiatric Consultation Service. AB - The Baffin Consultation Service of the Clarke Institute of Psychiatry has been providing psychiatric consultation services to the Baffin Island region of the Eastern Canadian Arctic since 1971. This report describes the background history, development and evolution of the service. Attention is focused on aspects of the consultation visits, educational activities of the project and the development of a mental health network. It is suggested that this is a useful model for the provision of psychiatric services to remote areas with limited resources. PMID- 8448714 TI - Changes in appetite and weight during the pharmacological treatment of patients with panic disorder. AB - Antidepressants reportedly increase appetite, carbohydrate craving and weight in some patients with depression and panic disorder. This paper presents the results of changes in appetite and weight in patients with panic disorder treated with imipramine, diazepam or placebo in a double-blind prospective study. Forty-four patients with panic disorder were randomly assigned imipramine, diazepam and placebo. The investigators monitored weight and the patients rated their appetite and cravings during the eight week study. No significant increases in weight or appetite were found in the patients with panic disorder patients. PMID- 8448716 TI - Psychiatric consultation in the eastern Canadian Arctic: II. Referral patterns, diagnoses and treatment. AB - The clinical activities of the Baffin Consultation Service of the Clarke Institute of Psychiatry were examined. Demographic and clinical data are described based on clinical interviews and questionnaire items from 581 initial psychiatric referrals. More women than men were referred to the service; the mean age of the patients seen was 27.3 +/- 13.4 years. The majority of referred patients were single and unemployed. The most common reasons for referral were depression, suicidal ideation, suicide attempts and family problems. The major diagnoses made were adjustment reactions and depressive disorders. Treatment was largely carried out in an outpatient setting through local health care professionals. The implications of these findings for this population and the development of community-based intervention programs are discussed. PMID- 8448717 TI - Psychiatric consultation in the eastern Canadian Arctic: III. Mental health issues in Inuit women in the eastern Arctic. AB - This report describes mental health issues affecting Inuit women as seen in psychiatric consultation. Recent public and governmental attention has focused on the emotional and behavioural sequelae of rapid cultural change, spousal assault and sexual violence. The process of psychiatric consultant with the Inuit woman patient will be described. The need for innovative, community-based treatment strategies in this population will be emphasized. PMID- 8448718 TI - To what extent do anxiety and depression interact with chronic pain? AB - In 61 patients with generalized musculoskeletal pain, severity of anxiety and depression correlated significantly with self-reported impact of illness and physician-rated disability. Depression was significantly associated with pain frequency, whereas anxiety was unrelated. Depressed mood was more closely tied to patients' ability to function than to their experience of pain. PMID- 8448720 TI - Successful treatment of litigious paranoia with pimozide. AB - A case of querulous-litigious delusional disorder successfully treated with low dose pimozide is reported. A summary of the contemporary literature on this neglected topic is provided. PMID- 8448719 TI - Effects of treatment and alternative care on length of stay on a general hospital psychiatric unit--results of an audit. AB - Quality controls are becoming an important part of our health care system. A medical audit is one way of evaluating quality of care, and this paper describes the results of an audit conducted to investigate the reasons for a prolonged stay on a psychiatric inpatient unit. The results showed a decrease in the mean length of stay over a five year period, although the figure remained substantially above provincial norms. A review of the hospital charts of a random sample of one in six patients whose hospital stay exceeded 30 days was carried out. It revealed that in 50.0% of cases the reasons were "medically acceptable," in 10.3% the reasons were "medically unacceptable" and in 39.7% the reasons were "social and administrative" and beyond the control of the treating psychiatrist. The implication of these results are discussed. PMID- 8448721 TI - The mental health of Portuguese children. AB - This study investigated the mental health of Portuguese children in Canada. Preliminary work involved a survey of professionals serving the Portuguese community and the translation and assessment of a standardized child behaviour checklist. Forty-five Portuguese children and 45 non Portuguese children referred to a children's mental health centre were compared on demographic and family indicators and their referral source. There were similar proportions of boys and girls in the two groups, similar types of services were requested, and they had similar treatment histories. The Portuguese children were older at the time of referral and were more likely to be referred by educational agencies than the non Portuguese children. Portuguese families appeared to experience different stresses than non Portuguese families. Implications of these findings for the provision of culturally sensitive interventions for Portuguese children and their families are discussed. PMID- 8448722 TI - [Anorexia nervosa in a prepubescent child]. AB - Anorexia nervosa in prepubescent patients is a serious pathology, which is often misunderstood, not exceptional and on the increase. Our study focuses on 13 case histories of children between eight and 12 years of age who met Tanner's first criterion (absence of puberty) and presented a substantial weight loss and a morbid fear of gaining weight. More specifically, we studied in our sample the general epidemiological data, the clinical features related to development (effect on growth, refusal of hydration), depressive comorbidity and a rather deteriorating evolution for the majority of our patients. Our results were compared with the data from the literature. PMID- 8448723 TI - Acute psychosis associated with oral trimethoprim-sulfamethoxazole therapy. AB - A 74 year old woman became progressively confused and developed visual hallucinations and delusions over a six day period, after the institution of routine oral trimethoprim-sulfamethoxazole therapy for a urinary tract infection. The medication was discontinued, and a marked improvement was noted 36 hours later. There was a complete return to normal mental functioning 60 hours after therapy was discontinued. The relationship between the patient's symptoms with the initiation and discontinuation of the medication suggests that the drug had a causal effect. PMID- 8448724 TI - Stature, drive for thinness and body dissatisfaction: a study of males and females from a non clinical sample. AB - A study of 174 subjects selected from a Canadian shopping mall revealed an inverse correlation among the males but not among females between body stature and body image parameters related to dieting, body weight and shape (for example, drive for thinness, and body dissatisfaction). These correlations were independent of body weight. Among the females, there was a direct correlation between the Body Mass Index and these body image parameters. Height is generally associated with desirable looks and academic success among men and most likely has a positive effect upon body image. Therefore, males who are dissatisfied with their stature, a feature that is generally not within their control, may attempt to alter an aspect of their body that they can control (for example, weight). This finding may have important implications among males with eating disorders. PMID- 8448725 TI - Possible interaction between fluoxetine and pimozide causing sinus bradycardia. AB - Fluoxetine has been reported to have interactions with antipsychotics and other antidepressants with symptoms of toxicity of these drugs. We report a case of a possible interaction with pimozide which led to a potentially life threatening bradycardia. Careful monitoring should be done when these two drugs are prescribed at the same time, especially in the elderly and in patients with cardiac disease. PMID- 8448726 TI - Fregoli syndrome of the self. PMID- 8448727 TI - The use of antidepressants in the treatment of children with behaviour disorders. PMID- 8448728 TI - Psychiatric emergency services in Canada. PMID- 8448729 TI - Weight gain with clozapine treatment. PMID- 8448730 TI - A study of intramuscular clonazepam for psychotic agitation. PMID- 8448731 TI - Group processes, changes and sanity. PMID- 8448732 TI - Monitoring of lithium prophylaxis. PMID- 8448733 TI - An introduction to multivariate statistics. AB - The more commonly known statistical procedures, such as the t-test, analysis of variance, or chi-squared test, can handle only one dependent variable (DV) at a time. Two types of problems can arise when there is more than one DV: 1. a greater probability of erroneously concluding that there is a significant difference between the groups when in fact there is none (a Type I error); and 2. failure to detect differences between the groups in terms of the patterns of DVs (a Type II error). Multivariate statistics are designed to overcome both of these problems. However, there are costs associated with these benefits, such as increased complexity, decreased power, multiple ways of answering the same question, and ambiguity in the allocation of shared variance. This is the first of a series of articles on multivariate statistical tests which will address these issues and explain their possible uses. PMID- 8448734 TI - The Intergroup Rhabdomyosarcoma Studies come of age. PMID- 8448735 TI - Treatment of oral Kaposi sarcoma with intralesional vinblastine. AB - BACKGROUND: Kaposi sarcoma (KS) is an acquired immune deficiency syndrome defining condition in human immunodeficiency virus infection. Oral KS may produce local symptoms and require treatment. Palliation of oral lesions may be achieved with radiation therapy and chemotherapy. This review was conducted to assess the effect of intralesional vinblastine in the management of oral KS. METHODS: Patients were referred because of oral KS. Intralesional injection of vinblastine (0.2 mg/ml) was conducted under local anesthesia, and patients were observed to determine the effect of treatment. RESULTS: Forty-two patients with oral KS were treated with intralesional vinblastine. A greater than 50% reduction in the lesions was seen in 74% of patients. The mean duration of response was 3.52 months for all patients. For patients not lost to follow-up and observed until recurrence of the oral lesions, palliation was achieved for a mean of 4.25 months. CONCLUSIONS: Effective local palliation of oral KS can be achieved with intralesional injection of vinblastine. PMID- 8448736 TI - Treatment of carcinoma of the esophagus with 5-fluorouracil and recombinant alfa 2a-interferon. AB - BACKGROUND: Combinations of 5-fluorouracil (5FU) and recombinant alfa-2a interferon (IFN) are synergistic in vitro and have demonstrated activity in colorectal carcinoma, renal cell carcinoma, and urothelial tumors. METHODS: A Phase II trial of the combination of 5FU, 750 mg/m2 daily x 5 followed by weekly bolus therapy, and IFN, 9 MU subcutaneously three times per week, was initiated in patients with esophageal carcinomas. Patients were required to have biopsy proven squamous cell or adenocarcinoma of the esophagus, locally advanced or metastatic disease beyond the scope of surgical resection, and adequate performance status, renal, hepatic, and bone marrow function. RESULTS: Twenty-one patients were enrolled; one patient was inevaluable for response because he had received prior chemotherapy, but was evaluated for toxicity. Eleven patients had metastatic disease, and 10 had locally advanced disease. Thirteen patients had squamous cell carcinoma and 8 adenocarcinoma. Toxicities were acceptable with no serious diarrhea and only two cases of serious stomatitis, although a greater than expected incidence of neurologic toxicity was observed. There were five responders (25%) including two patients with advanced or locally advanced disease rendered pathologically free of disease. One patient, initially considered surgically unresectable, was able to undergo a total thoracic esophagectomy after responding to treatment with 5FU/IFN, at which time only a single microscopic focus of carcinoma in situ was found. She remains alive and free of disease at 18+ months. A second patient who presented with metastatic disease and nearly complete obstruction of the esophagus regained normal swallowing function after treatment with 5FU/IFN; rebiopsy of all lesions revealed the patient to be pathologically free of disease. He survived over 2 years. CONCLUSIONS: This regimen employing a single cytotoxic agent has activity in esophageal carcinoma. Strategies employing biochemical modulation deserve additional investigation in the treatment of esophageal carcinoma. PMID- 8448737 TI - Dietary factors and gastric cancer risk. A case-control study in Spain. AB - BACKGROUND: Evidence supports that gastric cancer has an environmental etiology, of which diet appears to be the most important component. The authors examined the effect of diet on the risk of gastric cancer. METHODS: A case-control study of dietary factors and gastric cancer was conducted between September 1986 and March 1989 in the Barcelona metropolitan area, Spain. One hundred seventeen cases with histologically confirmed diagnosis of gastric adenocarcinoma were matched by age, gender, and whether they possessed a telephone to 234 community controls. One hundred eighty-eight (80.3%) controls were selected by random-digit telephone dialing and 46 (19.7%) by neighborhood of residence. Information about frequency and amount of consumption of 89 food items in one year was gathered by using a questionnaire, and cases and controls were interviewed in their homes by trained interviewers. Unconditional logistic regression was used for the analysis. RESULTS: Gastric cancer risk rose with increasing intake of smoked and pickled foods (OR 3.67 for upper tertile) and salt (OR 2.11 for upper quartile). Intake of citrus fruits (OR 0.47 for upper tertile) and raw-green vegetables (OR 0.56 for upper quartile) appeared to be protective. Gastric cancer risk was not associated with intake of cereals, rice, total vegetables, and fruits as a whole. CONCLUSIONS: These data suggest that high intake of salt and smoked and pickled food may be associated with a high risk of gastric cancer, and this association could be due to intragastric formation of nitrosamines. The negative association with citric and green vegetables consumption to be associated with the inhibition of nitrosation process. PMID- 8448738 TI - External radiation therapy without chemotherapy in the management of anal cancer. AB - BACKGROUND: Most therapeutic regimens currently in use for sphincter preservation in anal cancer utilize combined radiation therapy and chemotherapy. To provide a basis for comparison with combined therapy results, an analysis was made of patients treated with external radiation therapy without chemotherapy. METHODS: Eighteen patients with squamous cell, basaloid, or cloacogenic carcinoma of the anal canal were treated with external radiation therapy between January 1, 1980, and December 31, 1989, with the goal of sphincter preservation and cure. Before radiation therapy, five patients had incisional biopsies, two underwent piecemeal removal of the tumor, three had excisional biopsies with positive margins, five had excisional biopsies with negative margins, and three had excisional biopsies with unknown margins. All patients received 45 to 50 Gy in 25 to 28 fractions to the pelvis and perineum, and 16 of the 18 received an additional boost to the primary site to bring the total dose to 55 to 67 Gy in 30 to 38 fractions. RESULTS: With follow-up of 2.5 to 11.2 years in surviving patients, 5-year projected survival and freedom from local recurrence were 94% and 100%, respectively. Two patients required a temporary colostomy because of treatment complications. No patient required a permanent colostomy or had permanent loss of anal sphincter function as a result of local recurrence or complications. CONCLUSIONS: These results, combined with others, suggest that external radiation therapy without chemotherapy is an acceptable alternative to combined radiation therapy and chemotherapy in the management of anal cancer. PMID- 8448739 TI - Nocardiosis after corticosteroid therapy for malignant thymoma. AB - BACKGROUND: Nocardia asteroides is an opportunistic infection caused by an aerobic actinomycete, which, in the immunocompromised host, can be associated with severe invasive disease with a predilection for the brain. METHODS AND RESULTS: The authors describe a 62-year-old man with a malignant thymoma that was clinically responsive to oral prednisone. N. asteroides sepsis subsequently developed, leading to his death. CONCLUSIONS: Nocardiosis should be considered a potential pathogen in this immunocompromised setting. PMID- 8448740 TI - Sarcomas of the great vessels. A clinicopathologic study. AB - BACKGROUND: There are few reports comparing the clinicopathologic features of sarcomas of the aorta (SA), sarcomas of the inferior vena cava (SIVC), and sarcomas of the pulmonary artery (SPA). METHODS: The authors retrospectively reviewed 11 SA, 16 SIVC, and 16 SPA, and compared clinical, pathologic, and immunohistochemical findings. RESULTS: The mean age at presentation for SA was 62.3 +/- 17.3 years versus 41.3 +/- 17.1 for SPA; mean age for SIVC was 49.9 +/- 18.8. Nine of 11 SA and 14 of 16 SPA were grossly confined to the lumen, compared with only two SIVC. Luminal sarcomas were classified as poorly differentiated (intimal), angiosarcoma or leiomyosarcoma. Eight SA, 13 SPA, and one SIVC were of the intimal type and were composed of fibroblastic or myofibroblastic cells; five had "storiform" areas typical of malignant fibrous histiocytoma, and all had areas of necrosis. Intimal SPA were more likely myxoid than SA, and osteosarcomatous differentiation was present only in SPA (three cases). Intimal sarcomas were negative for desmin, Factor VIII-related antigen, S-100 protein, and CD34/QBend; all were positive for vimentin and most showed positive cells for smooth muscle actin. One luminal SA and one luminal SPA were histologically typical of angiosarcoma. Two SPA, 2 SA, and 14 SIVC were predominantly mural, most of which were leiomyosarcomas. The mean survival of intimal SA was poor (5 months), compared with 37 months for SIVC and 23 months for intimal SPA. CONCLUSION: SA, SPA, and SIVC differ in their clinical presentation and survival. Most SA and SPA sarcomas are aggressive, probably derived from intimal cells that show myofibroblastic differentiation. SIVC are usually derived from medial smooth muscle and are relatively well differentiated leiomyosarcomas. PMID- 8448741 TI - Results of salvage mastectomy for local recurrence after breast-conserving surgery without radiation therapy. AB - BACKGROUND: Between 1975 and 1987, 128 patients with infiltrating breast cancer, categorized as clinical Stage I and II disease, were treated by breast conservation surgery without radiation therapy. MATERIALS: After a median disease free interval of 20 months (range, 8-64 months), 25 of 128 patients had local recurrence, for which salvage mastectomy was performed. The results of modified radial mastectomy as a salvage procedure were analyzed in these 25 patients. RESULTS: After a median disease-free interval of 52 months (range, 8-75 years) after the salvage procedure, 12 patients had chest wall and distant recurrences, whereas 13 patients remained free of disease. The 5-year actuarial disease-free and overall survival rates after the salvage mastectomy were 51% and 65%, respectively. CONCLUSIONS: Univariate analyses of factors affecting disease-free survival and overall survival showed that the size of the local recurrence (< or = 2 cm) (P = 0.009) and the number of pathologically positive axillary nodes at the time of the salvage procedure (fewer than four nodes) (P = 0.002) were associated with a better prognosis. PMID- 8448742 TI - Overall survival from breast cancer in Kerala, India, in relation to menstrual, reproductive, and clinical factors. AB - BACKGROUND: Breast cancer accounts for one-fourth of cancer cases seen in female patients in Kerala, India. Results of a retrospective analysis of breast cancer in Kerala are presented in this article. METHODS: Case records of 449 patients with breast carcinoma treated during 1983-1984 were reviewed. Survival analysis was done by the Kaplan-Meier product limit method. The survival curves were compared by the log-rank test. A forward stepwise procedure with the Cox proportional hazards regression analysis was performed to identify factors influencing survival. RESULTS: The overall 5-year survival rate was 40%. The 5 year survival rates were 85% for patients with T1, 63% for T2, 32% for T3, and 21% for T4 lesions. Those with N0 disease had a 68% 5-year survival rate. The survival rates were 90% for patients with Stage I, 65% for Stage II, 33% for Stage III, and 6% for Stage IV disease. On multivariate analysis, the following factors were found to significantly influence survival: response to treatment (P < 0.001), stage (P < 0.01), and regional nodal involvement (P < 0.05). CONCLUSIONS: Two-thirds of patients with advanced-stage disease on presentation seem to account for the poor overall survival. Early detection of breast cancer by breast self-examination and physician breast examination should be encouraged in developing countries to improve treatment results in breast cancer. PMID- 8448743 TI - Mammography use and outcomes in a community. The Greater Lansing Area Mammography Study. AB - BACKGROUND: Mammography is widely known to reduce morbidity and mortality from breast cancer, but a population-based assessment of mammography use and follow-up of mammography findings has not been reported previously. METHODS: An observational, population-based, follow-up study was conducted of all women having mammograms in the Greater Lansing, Michigan, metropolitan area, between June 1987 and June 1988. A total of 17,811 Greater Lansing women participated. The adherence of women to mammography screening guidelines was estimated, and mammography's utility to detect breast cancer was assessed through follow-up review of breast biopsy results. RESULTS: Thirty-seven percent of the expected number of women 35 years of age and older had mammograms. Adherence to screening guidelines declined with age, and less than 5% (302 of 6700) of women 55 years of age and older reporting having annual mammograms. Seventy-six percent of women reported that their physicians prompted the examination. The predictive value of a positive mammogram was 21.9% for women without symptoms and 32.4% for women with symptoms. Mammography's sensitivity and specificity for breast cancer detection were 71% and 98%, respectively. CONCLUSIONS: The study highlights the need to target mammography to women 50 years of age and older, underscores the importance of physicians in promoting mammography, and demonstrates the analytic value and limitation of mammography in clinical decision-making. PMID- 8448744 TI - Interferon-alpha antibodies in patients with renal cell carcinoma treated with recombinant interferon-alpha-2A in an adjuvant multicenter trial. The Delta-P Study Group. AB - BACKGROUND: Prolonged therapy with interferon (IFN) may lead to the formation of IFN antibodies. METHODS: Patients with renal cell carcinoma (n = 270) with advanced localized disease were randomized after complete tumor resection to receive treatment with adjuvant recombinant IFN-alpha-2a (rIFN-alpha 2a) (9 x 10(6) IU subcutaneously, three times per week for a maximum of 12 months) versus no treatment. Patients (IFN-treated group, 106 patients; control group, 97 patients) were monitored for the presence of rIFN-alpha 2a antibodies. RESULTS: Of 86 IFN-treated patients observed for more than 2 months, 40 (47%) had IFN alpha 2a-binding and 25 (29%) had IFN-alpha 2a-neutralizing antibodies developed within a median of 3 and 6 months, respectively. A distinct peak in binding antibody titers occurred at 6-9 months. Therapy-induced neutralizing antibodies were equally reactive with two other recombinant IFN-alpha-2 subtypes but poorly recognized natural IFN-alpha (IFN-alpha), recombinant IFN-alpha-1/alpha-8, and recombinant IFN-omega-1. The duration of remission and rate of relapse were independent of the antibody status, although neutralizing and most non neutralizing antibodies correlated with a reduction in the IFN-induced increase in beta-2-microglobulin levels. CONCLUSIONS: Patients treated with IFN-alpha 2a should be monitored for the presence and clinical relevance of IFN-alpha antibodies to determine those who could respond to alternative treatment. PMID- 8448745 TI - Transitional cell carcinoma of the renal pelvis with choriocarcinomatous differentiation. Immunohistochemical and immunoelectron microscopic assessment of human chorionic gonadotropin production by transitional cell carcinoma of the urinary bladder. AB - BACKGROUND: There have been 12 documented cases of choriocarcinoma arising in the urinary bladder, either alone or in combination with other epithelial tumors. It has been shown that some high-grade transitional cell carcinomas (TCC), without obvious syncytiotrophoblastic elements, can produce human chorionic gonadotrophins (HCG). METHODS: A case of choriocarcinoma, in association with high-grade TCC of the renal pelvis, was encountered in an 80-year-old man. For additional evaluation of HCG production by TCC, 25 consecutive cases of invasive high-grade TCC of the bladder were stained with an anti-HCG antibody. Immunogold staining also was performed in two of the cases studied. RESULTS: Immunoperoxidase staining of the renal pelvis tumor showed focal positivity for HCG within the TCC and a more intense reaction as the tumor cells differentiated into choriocarcinoma elements. Seven of the 25 cases (28%) displayed varying degrees of reactivity within individual cells or groups of cells. In an additional case, typical syncytiotrophoblastic giant cells without cytotrophoblasts were seen in a high-grade TCC. Immunogold studies demonstrated positive labeling in the cytoplasm of carcinoma cells in a case of TCC without syncytiotrophoblasts and in the syncytiotrophoblastic giant cells in the one case in which these were present. CONCLUSIONS: The findings support a metaplastic origin of cases of choriocarcinoma arising primarily in the urothelial tract. PMID- 8448747 TI - Pulmonary granulomata. A complication of intravesical administration of bacillus Calmette-Guerin for superficial bladder carcinoma. AB - Intravesical administration of bacillus Calmette-Guerin (BCG) is an effective treatment for superficial carcinoma of the bladder. The authors report a pulmonary complication characterized by miliary infiltration on chest roentgenogram and caseating granulomata on lung biopsy specimens. This case and three prior reports suggest that this complication may be a form of hypersensitivity rather than true BCG infection. PMID- 8448746 TI - Prophylactic oral UFT therapy for superficial bladder cancer. AB - BACKGROUND: A randomized prospective trial was performed to determine whether long-term oral UFT (a 1:4 mixture of tegafur and uracil) (Taiho Pharmaceutical Co., Tokyo, Japan) therapy was effective in preventing the intravesical recurrence of superficial bladder cancer. METHODS: A total of 112 patients with newly diagnosed superficial transitional cell carcinoma of bladder (Ta, T1 and G1 or G2) were randomized into a UFT-treated group (300-400 mg/d for 2 years) and a control group. RESULTS: After a median follow-up period of 24.5 months, the recurrence rate was 25.7% for the UFT group and 43.3% for the control group (P = 0.015, log-rank test). Side effects of UFT administration were acceptably low. CONCLUSIONS: These results suggest that long-term UFT administration after transurethral resection is effective in preventing the recurrence of superficial bladder cancer. PMID- 8448748 TI - Use of pilocarpine during head and neck radiation therapy to reduce xerostomia and salivary dysfunction. AB - BACKGROUND: Salivary gland hypofunction commonly develops during radiation therapy to the head and neck region. This study evaluated whether the sialogogue pilocarpine given during radiation therapy may reduce the severity of xerostomia and salivary dysfunction. METHODS: Nine patients requiring head, neck, or mantle radiation therapy participated in this double-blind, placebo-controlled trial. The patients took either 5 mg of pilocarpine or placebo four times daily for 3 months, beginning the day before radiation therapy. Subjective complaints and salivary functions were assessed. RESULTS: The pilocarpine-treated group had a lower frequency of oral symptoms during treatment than the placebo-treated group. Although salivary flow decreased in all patients, the pilocarpine-treated group had smaller reductions in flow. No drug effect was observed in glands that were irradiated completely. Thus, pilocarpine appeared to stimulate salivary tissues outside the radiation field. CONCLUSIONS: These results suggest that stimulation with pilocarpine may reduce the severity of salivary dysfunction and associated oral symptoms during radiation therapy. PMID- 8448749 TI - Etoposide in combination as first-line chemotherapy for advanced Hodgkin disease. A Cancer and Leukemia Group B study. AB - BACKGROUND: In a pilot study, Cancer and Leukemia Group B (CALGB) incorporated etoposide into primary combination therapy for advanced Hodgkin disease. METHODS: Thirty-six evaluable patients were treated with two or three courses of methotrexate, vincristine, prednisone, leucovorin, etoposide, and cyclophosphamide (MOPLEC), and then treated with five to seven additional courses of a known "curative" regimen: nitrogen mustard, vinblastine, prednisone, and procarbazine (MVPP). RESULTS: After treatment with MOPLEC, there were 16 complete responders (44%) and 18 partial responders (50%). One patient had progressive disease and one patient was taken off study after an anaphylactic reaction to etoposide. After completing the entire protocol, 32 patients achieved complete remission (CR) (89%) and 3 achieved partial remission (PR) (8%). Five CR patients have relapsed and three additional patients have died in CR without recurrence. At 36 months, the estimated failure-free survival is 61% and overall survival is 72%. CONCLUSIONS: This combination, which includes etoposide, is active for the primary treatment of advanced Hodgkin disease. PMID- 8448750 TI - Hodgkin disease in patients 60 years of age or older. Histologic and clinical features of advanced-stage disease. The Cancer and Leukemia Group B. AB - BACKGROUND: This article reviews the salient pathologic and clinical features of 171 patients with Stage III-IV disease who were 60 years of age or older who were treated on four Hodgkin disease (HD) protocols from 1969 to 1988. METHODS: Pretherapy sections were reviewed centrally for correlation of the histologic classification with anatomic sites of involvement and survival. RESULTS: The diagnosis of HD was confirmed in 114 (66.7%) patients. Non-Hodgkin lymphomas (NHL) and a miscellaneous non-HD group accounted for 52 (30.4%) and 5 (2.9%) of the cases. The overall median survival times of patients with Stage III-IV HD and NHL who were 60 years of age or older in the four protocols were not significantly different (1.5 versus 1.3 years, respectively; P = 0.28). There also was no significant correlation between the survival of these patients with HD and either the Rye classification, 19 specific histologic parameters, or the British National Lymphoma Investigation grading system for HDNS. In the last protocol, the 5-year survival rate of patients with HD who were 60 years of age or older was lower than that of patients 40-59 years of age or that of those younger than 40 years of age (31% versus 63% versus 79%, respectively, P < 0.0001). Patients with HD entered into the two most recent protocols showed lower incidences of involvement of cervical and iliac-inguinal-femoral lymph nodes and skin-subcutaneous tissues than the patients with NHL who were misdiagnosed as HD. Moreover, patients with Stage III-IV HD in the most recent protocol who were 60 years of age or older had lower rates of involvement of the cervical and mediastinal-hilar lymph nodes and a higher rate of involvement of the gastrointestinal tract than younger patients. CONCLUSIONS: Patients with Stage III-IV HD and NHL who are 60 years of age or older differ with respect to the rates of involvement of specific anatomic sites but not in survival when treated with HD protocols. In contrast, patients of different age groups with Stage III IV HD disease differ with regard to the rates of involvement of anatomic sites and survival. PMID- 8448751 TI - The cost of cancer home care to families. AB - BACKGROUND: For the most part, previous research on costs of cancer care has focused on the formal medical care costs. Research on home care for patients with cancer has emphasized direct care costs (expenditures). Among indirect costs, only loss of income to family members has been studied. However, a major component of indirect costs, the family labor expended to care for the patient with cancer, needs to be included for a more realistic appreciation of home care costs. METHODS: The costs of family labor are estimated by imputing monetary values for the time spent caring for the patient with cancer. The assigned monetary cost either is equated with income losses of the helper in question or is based on a putative market value of the expended labor time. In addition, out of-pocket expenditures examined in this study cover all cancer care-related expenses for which the patient was not reimbursed by third parties. Data were obtained from a convenience sample of 192 patients with cancer and their families in lower Michigan. RESULTS: When family labor is included in the cost calculations, average cancer home care costs for a 3-month period ($4563) are not much lower than the costs of nursing home care. The substantial variation in home care costs (standard deviation [SD] = $4313) appears to be unrelated to the type of cancer diagnosis, type of treatment, or time since diagnosis but seems to be driven by the functional status of the patient and the family living arrangements. CONCLUSIONS: Outpatient care for patients with cancer coupled with greater reliance on home care appear to be economically attractive because costs to families usually are underestimated. PMID- 8448752 TI - Uridine allows dose escalation of 5-fluorouracil when given with N-phosphonacetyl L-aspartate, methotrexate, and leucovorin. AB - BACKGROUND: In a previous trial in which methotrexate and N-phosphonacetyl-L aspartate (PALA) were used to modulate 5-fluorouracil (5-FU), four of six patients could not tolerate treatment at the 600 mg/m2 5-FU dose level because of mucositis, diarrhea, and a decrease in performance status. The current study examines the ability of uridine rescue to prevent such toxic effects in the same regimen and, thereby, allow additional dose escalation of 5-FU. METHODS: Twenty nine patients with advanced malignant neoplasms received PALA and MTX, each at 250 mg/m2, followed 24 hours later by increasing bolus doses of 5-FU (600-750 mg/m2) with a leucovorin rescue (10 mg orally every 6 hours for eight doses) and uridine rescue (3 g/m2/hour, for a 72-hour infusion, 3 hours on, 3 hours off). Treatment was repeated weekly with either 2 weeks on, 2 weeks off, or 3 weeks on, 1 week off. RESULTS: Mucositis, which occurred in 4 of 12 patients treated at the 750 mg/m2 5-FU dose level, was the only significant chemotherapy-induced toxic effect. However, uridine-related central venous catheter complications (cellulitis in six patients and superior vena cava syndrome in one patient) precluded additional treatment on this protocol. CONCLUSIONS: In the current regimen, uridine allowed dose escalation of 5-FU to 750 mg/m2, which some patients tolerated on a 3-week on, 1-week off schedule. Because of the vascular toxic effects associated with intravenous uridine, the authors recommend additional studies with oral uridine to determine whether the increase in 5-FU dose that uridine allows is associated with improved response rates. PMID- 8448753 TI - Treatment of cancer chemotherapy-associated thrombotic thrombocytopenic purpura/hemolytic uremic syndrome by protein A immunoadsorption of plasma. AB - BACKGROUND: Chemotherapy-associated thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (C-TTP/HUS) is a condition involving thrombocytopenia, microangiopathic hemolytic anemia, and progressive renal dysfunction that develops in 2-10% of patients with a history of malignant neoplasms treated with certain chemotherapeutic agents. Pathogenesis of the disease may depend on the following: (1) generation of endothelial lesions in the kidney microvasculature, resulting from drug toxic effects and/or generation of small soluble circulating immune complexes (CIC), and (2) generation of autoantibodies and/or CIC that trigger aggregation and deposition of platelets around the lesions. METHODS: Extracorporeal immunoadsorption treatment of plasma (PROSORBA columns, IMRE Corporation, Seattle, WA) to remove immunoglobulin G and CIC was evaluated in 55 patients for the potential to induce significant clinical benefits (increase in platelet count, decrease in hemolysis, stabilization of renal function) and longer survival. RESULTS: Response to therapy was achieved in 25 of 55 patients examined. Response was associated with an estimated 1-year survival rate of 61%, as compared with an estimated survival rate of only 22% in those who did not respond (P = 0.0001). Patients whose malignant neoplasms were in complete or partial remission at the time of development of C-TTP/HUS had a significantly higher estimated 1-year survival rate (74%) as compared with a historic control group of patients receiving other treatments (22%, P = 0.0161). Clinical responses were correlated with normalization of serum levels of CIC and complement components C3c and C4. There were no side effects associated with 75% of treatments. Immunoadsorption therapy was associated with generally mild to moderate manageable side effects, such as fever, chills, nausea/vomiting, respiratory symptoms, pain, hypertension, and hypotension, which were reported in 25% of procedures. CONCLUSIONS: This multicenter study establishes protein A immunoadsorption as an effective and safe treatment for cancer chemotherapy associated TTP/HUS, an otherwise fatal disease. PMID- 8448754 TI - Malignant melanoma of the vulva and vagina. Trends in incidence, age distribution, and long-term survival among 245 consecutive cases in Sweden 1960 1984. AB - BACKGROUND: Malignant melanomas of the vulva and vagina are rare tumors located in areas of the body not exposed to ultraviolet radiation. Investigations comprising large consecutive population-based series of patients with these diseases have not been published previously, to the knowledge of the authors. METHODS: Trends in incidence, age distribution, and prognosis were investigated among 219 consecutive cases of malignant melanoma of the vulva and 26 cases in the vagina, reported to the Swedish National Cancer Registry and representing virtually all primary tumors of that kind in Sweden during a 25-year period, 1960 1984. RESULTS: On average, 75% of the patients with vulvar melanoma and 73% with vaginal melanoma were older than 60 years of age. The mean age increased slightly but not significantly during the period. The age-standardized incidence of vulvar melanoma decreased from 0.27 to 0.14 per 100,000 Swedish women, or by 3% per year. The observed 5-year survival rate of patients with vulvar melanoma was 35%, and the relative survival rate was 47%. The observed and relative survival rates at 10 years were 23% and 44%, respectively. Observed and relative survival rates among patients with vaginal melanoma after 5 years were 13% and 18%, respectively. CONCLUSIONS: Accordingly, there was a decreasing incidence of vulvar and vaginal melanoma over the observed 25 years. This is in contrast to the trends in incidence for cutaneous melanomas in Sweden, which, during the same time period, increased almost 6% per year. PMID- 8448755 TI - Ifosfamide/etoposide combination in the treatment of recurrent malignant solid tumors of childhood. A Pediatric Oncology Group Phase II study. AB - BACKGROUND: The prognosis for children with recurrent or resistant malignant solid tumors remains dismal. More effective rescue therapy is needed for these children. METHODS: Between August 1987 and November 1990, 311 children with recurrent or resistant malignant solid tumors were treated by investigators in the Pediatric Oncology Group with intravenous infusions of 2.0 g/m2 of ifosfamide and 100 mg/m2 of etoposide (VP-16) plus mesna as uroprotection three times daily, with courses being repeated every 14-21 days for as long as the patients responded to therapy. RESULTS: Seventy-four percent of the 294 assessable patients entered in the study had metastatic disease and previously had been treated heavily. The complete response/partial response rate was 30%, and the overall response rate was 39.5%. Toxic effects included nephrotoxicity, mild liver dysfunction, neurotoxicity, and myelosuppression. Sixty-eight percent had an absolute neutrophil count (ANC) of less than 500/microliters. In 1606 courses of therapy administered, only 3.6% of patients developed a bacterial infection. Only two patients died of gram-negative sepsis. Four percent of the patients had gross hematuria (> 50 erythrocytes/high-power field), and 18.5% had microscopic hematuria (< 20 erythrocytes/high-power field). Fanconi syndrome developed in eight children. CONCLUSIONS: Ifosfamide/VP-16 is an active combination in children with recurrent malignant solid tumors. Although it was myelosuppressive, the incidence of infection was quite low (3.6%). Mesna was very effective in preventing the development of hematuria. PMID- 8448757 TI - Parathyroid crisis of unusual features in a child. AB - BACKGROUND: A case of familial parathyroid crisis resulting from presumptive cancer in a 14-year-old boy impressed the authors with its rarity and need for recognition. METHODS: The authors performed a retrospective review of the relevant literature and described the case. RESULTS: The case report cited is the eighth example of parathyroid cancer occurring in a child younger than 16 years of age. It represents the first example of malignant parathyroid crisis because of familial hyperparathyroidism and illustrates the demand for appropriate diagnosis and methods of management in parathyroid cancer. CONCLUSIONS: Familial hyperparathyroidism may become manifest in young patients, which justifies screening among affected families to avoid serious sequelae of disease. Parathyroid cancer is an example of a malignant neoplasm in the young and is managed best by en bloc resection of primary disease, appropriate neck dissection for nodal involvement, and aggressive resection for recurrence, if possible, to control the lethal effects of hypercalcemia; this permits prolonged survival even in discouraging situations. PMID- 8448756 TI - The Intergroup Rhabdomyosarcoma Study-II. AB - BACKGROUND: Intergroup Rhabdomyosarcoma Study (IRS)-II, (1978-1984) had the general goals of improving the survival and treatment of children with rhabdomyosarcoma (RMS). METHODS: Nine hundred ninety-nine previously untreated eligible patients entered the study after surgery and were randomized or assigned to therapy by IRS Clinical Group (I-IV), tumor site, and histologic type. Outcomes were compared between treatments and with results of IRS-I (1972-1978). RESULTS: Patients in Group I, excluding extremity alveolar (EA) RMS, were randomized to standard vincristine (V), dactinomycin (A), and cyclophosphamide (C) or standard VA. At 5 years, disease-free survival (DFS) and survival (S) rates were similar between VAC and VA (DFS: 80%, 70%, P = 0.47; S: 85%, 84%, P = 0.73). Patients in Group II, excluding EA RMS, received radiation and were randomized to intensive VA or repetitive-pulse VAC. Outcomes were similar for rates of DFS (69%, 74%, P = 0.83) and S (88%, 79%, P = 0.17). Patients in Group III, excluding certain pelvic tumors, received radiation and were randomized to repetitive-pulse VAC or repetitive-pulse VAdrC-VAC (Adr, Adriamycin [doxorubicin]). Complete remission (CR) rates were close at 74%, 78%, respectively (P = 0.32), as were percentages in CR (73%) and S (66%) rates; the latter outcomes were significantly better than IRS-I (CR: 56%, P < 0.001; S: 50%, P < 0.001). Central nervous system prophylaxis for Group III patients with cranial parameningeal sarcoma increased S rate to 67% from 45% in IRS-I (P < 0.001). Patients in Group IV received the same regimens as Group III; the CR rate was 53%, 38% remained in CR and S rate was 27% with and 26% without Adr (P = 0.90). At 5 years, S rate for IRS-II, including EA and all pelvic tumors, was 63%: an 8% increase over IRS-I (P < 0.001). Outcomes by primary site were as good as, or better than, the IRS-I experience. CONCLUSIONS: Combining all Groups and treatments in IRS-II, the major improvement in S rate at 5 years between studies was in nonmetastatic patients (71% for IRS-II versus 63% for IRS-I, P = 0.01). PMID- 8448758 TI - Spontaneous remission of infantile acute nonlymphocytic leukemia for 11 years in a child with normal karyotype. AB - BACKGROUND: Leukemia or a leukemia-like picture in phenotypically normal infants with a normal marrow karyotype who undergo spontaneous remission is extremely unusual. RESULTS: A 6-week-old, phenotypically normal boy first was seen in 1979 with hepatosplenomegaly, a 36 x 10(9)/l leukocyte count, a leukoerythroblastic picture, and increased blasts in the bone marrow aspirate. Because no other known causes of leukemoid reaction could be demonstrated, the picture was consistent at that time with acute nonlymphocytic leukemia (ANLL), French-American-British (FAB) M1; however, because of the age of the child, the low blast count, normal cytogenetics, and questions about this diagnosis, treatment was withheld. Hematologic laboratory values normalized by the time he was 1 year of age. Eleven years later, he presented a similar picture that rapidly progressed to overt leukemia (FAB M1). A normal marrow karyotype was consistent throughout the 11 years of follow-up. Treatment of ANLL was initiated, resulting in marrow remission. This was followed by allogeneic bone marrow transplantation. He had a relapse again and was retreated, achieving a second marrow remission, and had a second allogeneic bone marrow transplantation. However, the patient died of venoocclusive disease of the liver after the second transplant. CONCLUSION: The diagnosis and prognosis of infants with an abnormal hematologic picture similar to ANLL but who are phenotypically and karyotypically normal are not as straightforward as in the older child or adult. Treatment should be withheld in this setting until the leukemic process is overt. PMID- 8448759 TI - Risk factors for failure of immediate breast reconstruction with prosthesis after total mastectomy for breast cancer. PMID- 8448760 TI - Implementation of a large-scale picture archiving and communication system. AB - This paper describes the implementation of a large-scale picture archiving and communication system (PACS) in a clinical environment. The system consists of a PACS infrastructure, composed of a PACS controller, a database management system, communication networks, and optical disk archive. It connects to three MR units, four CT scanners, three computed radiography systems, and two laser film digitizers. Seven display stations are on line 24 h/day, 7 days/wk in genitourinary radiology (2K), pediatric radiology in-patient (1K and 2K) and outpatient (2K), neuroradiology (2K), pediatric ICU (1K), coronary care unit (1K), and one laser film printing station. The PACS is integrated with the hospital information system and the radiology information system. The system has been in operation since February 1992. We have integrated this PACS as a clinical component in daily radiology practice. It archives an average of 2.0-gigabyte image data per workday. A 3-mo system performance of various components are tabulated. The deployment of this large-scale PACS signifies a milestone in our PACS research and development effort. Radiologists, fellows, residents, and clinicians use it for case review, conferences, and occasionally for primary diagnosis. With this large-scale PACS in place, it will allow us to investigate the two critical issues raised when PACS research first started 10 yrs ago: system performance and cost effectiveness between a digital-based and a film based system. PMID- 8448761 TI - Integration of a voice processor machine in a PACS. AB - The final stage of development of a clinical picture archiving and communication system (PACS) at the University of California at Los Angeles (UCLA) department of radiological sciences consists of building a documentation package of a complete radiological consultation. In this paper, we present the technological aspect of the integration of a digital voice server in our PACS environment. This component improves the timely delivery of the diagnostic report with the images. The interface of this voice system is integrated into the PACS display station. It offers the user the capability to easily dictate and/or listen to radiological reports, while viewing and/or performing image processing operations at the display station. PMID- 8448762 TI - Model control of image processing: pupillometry. AB - Smart instruments require on-line computers, special purpose hardware, or both. A pupillometer is described that relies only on a general purpose microcomputer with a frame grabber to process infrared video camera pictures of the human eye. An essential feature of the instrument is that a top-down model controls the image processing algorithms. The model generates regions of interest, ROIs, positioned from knowledge of anatomy and optics of the eye and information from previously analyzed frames. Within these adaptively controlled ROIs, fast, run time algorithms automatically calculate local thresholds, area measurements, moments for centroid position information, and use pyramiding to shorten calculation time for large pupils. Outputs are precise measurements of pupil size and eye position in real time, with adequate bandwidth for most purposes. PMID- 8448763 TI - MRI of the brachial plexus: a review of 51 cases. AB - We present a magnetic resonance imaging (MRI) study in 51 patients where the brachial plexus was evaluated. Using a 1.5 T clinical imaging system, we obtained T1-weighted sequences, and double-echo (intermediate- and T2-weighted) spin-echo images. The coronal plane was imaged in all examinations and was supplemented by images in the sagittal and/or axial planes. Twenty cases had proven pathological brachial plexus involvement, whereas, in 31 cases, no brachial plexus involvement was present. In 4 cases, the MRI findings were not in agreement with the final diagnosis found in the charts. PMID- 8448764 TI - Complete avulsion of the triceps tendon: MRI diagnosis. AB - Avulsion of the triceps tendon is a rare injury. We report a case of complete avulsion of the triceps tendon diagnosed by magnetic resonance imaging (MRI) and confirmed surgically. The excellent soft tissue contrast and multiplanar imaging capability of MRI makes it an ideal tool to diagnose this disorder. To our knowledge, this is the first reported case of MRI diagnosis of complete avulsion of the triceps tendon. PMID- 8448765 TI - Sequential changes in MR images of the brain in acute carbon monoxide poisoning. AB - Two cases of acute carbon monoxide poisoning are presented in this paper. Sequential magnetic resonance (MR) images of the brain showed abnormal lesions in the bilateral globus pallidus and/or in the subcortical white matter. The MR images disclosed that the severity of the white matter lesions correlated with the prognosis in acute carbon monoxide poisoning. However, they did not always correspond to the neurological condition in the acute and subacute stages. PMID- 8448766 TI - Case report: massive biliary dilatation mimicking cystic retroperitoneal masses on computed tomography. AB - An unusual case is presented in which a massively dilated common bile duct produced a confusing CT image of multiple cystic areas within the abdominal cavity. Cholangiography and CT-cholangiography were useful in establishing the correct diagnosis. The differential diagnosis of cystic retroperitoneal masses is discussed. PMID- 8448767 TI - Microstructural changes of human enamel surfaces by brushing with and without dentifrice containing abrasive. AB - Toothbrushing with and without dentifrice containing abrasive was performed on human enamel pieces attached to resin plates exposed to the oral cavities of 3 human subjects for 8 weeks. The effects on the ground enamel surfaces with engraved scratches were examined by scanning electron and scanning laser microscopy. Brushing with such a dentifrice caused smaller scratches to disappear, large scratches to expand and new microwear to appear; in some samples, prism structures were exposed. Under brushing without dentifrice, these scratches were protected by an organic pellicle with mineral deposits, and also the experimental surface was entirely covered with these membranous deposits. The results indicate that toothbrushing with no dentifrice but saliva induces an organic-mineral protective membrane on the enamel surface. The membrane may increase the enamel resistance to caries. On the other hand, the use of abrasive containing dentifrice causes slight abrasion with microwear. This roughness may contribute to the formation of dental plaque. PMID- 8448768 TI - Rehardening of surface softened and surface etched enamel in vitro and by intraoral exposure. AB - The rehardening of surface-softened and surface-etched enamel was investigated in vitro and by intraoral exposure. Surface-softened enamel was obtained by treatment with 0.1 M acetic acid buffer solution (pH = 5.5) for 3 h. Surface etched enamel was obtained by the acid etch procedure used in clinical situations (37% phosphoric acid gel, 30 s). The enamel lesions were treated in vitro, with calcifying solutions for 8 h or were carried for 48 h in an intraoral appliance. Changes at the enamel surfaces were investigated by surface microhardness measurements. Following the treatment with calcifying solutions a significantly greater indentation length was observed in surface-etched than in surface softened enamel. No significant difference in indentation length between both types of enamel lesions was observed following intraoral exposure. It was concluded that the initial rate of rehardening between both types of enamel lesions is comparable. At his stage remineralization occurs in microspaces created in the slightly destroyed enamel structures. The influence of the etch pits on the indentation length becomes dominating when remineralization continues. An obliteration of etch pits was observed in enamel samples treated with the calcifying solution with the highest degree of saturation. It was suggested that freshly prepared highly supersaturated calcifying solutions can be used to enhance mineral appositions in accidental etch pits. PMID- 8448769 TI - Erosion by soft drinks of rat molar teeth assessed by digital image analysis. AB - A digital imaging analysis (DIA) procedure for recording and assessing erosive changes on teeth was developed and evaluated against an older subjective method. Results after exposure of rats' teeth to various soft drinks showed that the DIA system was superior to the conventional method, with improved precision. The system provided a direct and highly sensitive means of quantifying the erosion of dental hard tissues by three different soft drinks, showing that it could be used to evaluate erosiveness and other dental damage. After 6 weeks' exposure to soft drinks in the diet, the area of intact enamel on the lingual surface of the first mandibular molar averaged 47% on apple juice, 27% on still orange and 6% on carbonated orange. The greatest exposure of dentine (36%) was on the still orange drink. Eroded enamel accounted for 72.5% of the tooth surface on the carbonated drink. PMID- 8448770 TI - Mixed continuous cultures of Streptococcus mutans with Streptococcus sanguis or with Streptococcus oralis as a model to study the ecological effects of the lactoperoxidase system. AB - Mixed continuous cultures of Streptococcus species were obtained, using complex carbohydrate (mucin) as a source of nutrients, to study the ecological effects of oxygen and the lactoperoxidase system. S. mutans NCTC 10449 was unable to grow as a pure culture on mucin, but attained a significant population size in the presence of S. oralis and S. sanguis strains. The cell densities of the anaerobic mixed cultures decreased when oxygen was supplied, and S. mutans was more suppressed by oxygen than were S. sanguis and S. oralis. However, the concentrations of hydrogen peroxide (30 mumol/l in the mixed culture of S. mutans with S. sanguis and 640 mumol/l in the culture with S. oralis) indicated a certain resistance of the organisms to hydrogen peroxide. Addition of lactoperoxidase and thiocyanate to the oxygen-supplied cultures had a differential effect on the streptococcal populations. While S. mutans was inhibited, and even disappeared in the culture with S. oralis, the growth of S. sanguis and S. oralis was unaffected. This latter observation was in accordance with the OSCN- reductase activities of these organisms. When hydrogen peroxide was also added together with lactoperoxidase and thiocyanate, a further inhibition of S. mutans in the culture with S. sanguis was observed. Under these conditions, S. oralis was also inhibited, perhaps by the strong accumulation of OSCN-, exceeding the capacity of the OSCN- reductase. The effects of lactoperoxidase on mixed cultures may reflect the situation in the mouth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448771 TI - Effect of monoclonal antibodies on the colonization of rats by Streptococcus sobrinus. AB - Local passive immunization has been suggested as a method of preventing colonization of teeth by mutans streptococci. In this study we describe the effect of local application of monoclonal antibodies (Mabs) on the colonization of Streptococcus sobrinus. The rats, 37 days old, were divided in 4 groups: group 1 received Mab OMVU10 (Mab reactive with Antigen B of S. sobrinus, IgG2b), group 2 received Clone 24 (Mab reactive with lipid A of Escherichia coli, IgG2b), group 3 received uninoculated culture medium, and group 4 received phosphate-buffered saline (PBS). Mabs were applied 6 times on the surfaces of the molars and the labial surfaces of the incisors of the rats, on days 37, 40, 44, 46, 49 and 54 after birth. After the third application of Mabs, all rats were inoculated with S. sobrinus (day 45). Subsequently, the rats were fed a cariogenic diet containing 20% sucrose and 5% glucose. The rats were killed 34 days after inoculation and the maxillary molars were extracted and homogenized in order to determine the numbers of S. sobrinus. The proportions of S. sobrinus, expressed as a percentage of the total cultivable microflora, in rats which received OMVU10 (group 1) were 23.1 +/- 14.8%, whereas in rats which received Clone 24, culture medium or PBS the levels were 34.5 +/- 11.3%, 40.7 +/- 14.9% and 36.7 +/- 9.7%, respectively. Statistical analysis showed that the level of colonization of rats which received OMVU10 was significantly lower than that of rats which received Clone 24, culture medium or PBS (p < 0.001, p < 0.013 and p < 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448772 TI - Effect of sucrose rinses on the oral microflora and on salivary sucrase activity. AB - The effect of sucrose rinses on the salivary microflora and on bacterial sucrose cleaving, i.e., sucrase activity, was studied in 11 dental students with high salivary counts of mutans streptococci (> or = 10(5) CFU/ml). The subjects rinsed for 1 min with a 10% (w/v) sucrose solution every 4-h during waking hours on 2 consecutive days. Four paraffin-stimulated saliva samples were collected as follows: one before the rinses and then 12 h and 5 and 8 days after the rinses. Commercial dip-slide methods were used to determine viable counts of mutans streptococci, lactobacilli, and yeasts; mutans streptococci were also enumerated using MSB agar, while blood agar was used to recover the total facultative and anaerobic bacteria. The sucrase activity was determined using both whole (mainly cell-associated) and centrifuged (extracellular) saliva samples. The proportions of facultative bacteria (p = 0.007) and mutans streptococci (p = 0.001) increased as a result of the sucrose rinses. No changes were detected in the number of lactobacilli or yeasts. The sucrose rinses increased both the cell-associated (p = 0.049) and the extracellular (p = 0.011) sucrase activities. The measurement of sucrase activity may be of value in assessing dietary habits and sucrose consumption. PMID- 8448773 TI - pH changes in human dental plaque from lactose and milk before and after adaptation. AB - pH changes in human dental plaque in vivo from lactose and milk have been studied in four separate mouthrinse experiments. (1) pH was measured in plaque samples of 12 subjects before and after 6 weeks of frequent daily mouthrinsing with 10% lactose. The pH decreases were significantly more pronounced after the adaptation period than before (p < 0.001), 4 of the 12 subjects showing about the same low plaque pH from lactose as from glucose. (2) Similar to the previous experiment, frequent daily mouthrinsing with low-fat bovine milk in 10 subjects resulted in more pronounced pH decreases in plaque after an adaptation period of 4 weeks (p < 0.001). (3) Single mouthrinses, without any prior adaptation, with bovine standard milk, human breast milk, lactose-hydrolysed bovine standard milk, 5% lactose and 5% sucrose were compared regarding the effect on plaque pH in 7 subjects. All solutions resulted in pH falls. The most pronounced were found with sucrose, followed by the lactose-hydrolysed milk. (4) Bovine standard milk, 5% lactose and 10% sucrose were compared after a single mouthrinse in 5 subjects using interdental plaque pH wire telemetry. Lactose and milk were fermented more slowly than sucrose. In a separate study, acid production from lactose was also measured in two oral strains each of Streptococcus mutans, Streptococcus salivarius and Streptococcus sanguis. The results from these experiments indicated that at least part of the lactose transport and catabolism in all studied streptococcus strains seems to be regulated by inducible enzymes. PMID- 8448774 TI - Fluoride concentration in plaque adjacent to orthodontic appliances retained with glass ionomer cement. AB - The fluoride concentrations in dental plaque adjacent to orthodontic brackets retained with a glass ionomer cement (GIC) or a resin-based composite were investigated using the split-mouth technique. 48-hour plaque was collected at 3, 8, 28 days and 6 months after the onset of orthodontic treatment. The fluoride content of the plaque samples was determined after a microdiffusion procedure with a fluoride-sensitive electrode. Significantly (p < 0.001-0.05) elevated concentrations of fluoride were found in the plaque samples collected adjacent to GIC-retained brackets compared to plaque sampled from composite-retained brackets on all sampling occasions. The results suggest that GIC-bonded brackets in orthodontic treatment may act as local long-term fluoride-releasing devices. PMID- 8448775 TI - Effect of chewing xylitol chewing gum on salivary flow rate and the acidogenic potential of dental plaque. AB - Ten adults participated in the study which consisted of four experimental periods each lasting 2 weeks, during each of which subjects were assigned to one of four gum-chewing regimens: no gum, sucrose gum, sorbitol gum and xylitol gum. At the start and end of each test period unstimulated and stimulated salivary flow rates were determined. At the end of each test period the acidogenic potential of 48 hour dental plaque was measured using a Beetrode pH microelectrode. No statistically significant (p < 0.05) effect on salivary flow rate was observed. The xylitol chewing gum regimen resulted in significantly higher plaque pH than no gum, sucrose gum and sorbitol gum at 2, 10, 20, 30 and 60 min following a 10% sucrose rinse. In addition, xylitol gum regimen exhibited a significantly higher minimum pH and smaller area of the curve below pH 6. The results suggest that the regular use of xylitol-sweetened gum may serve to reduce the acidogenic potential of dental plaque. PMID- 8448776 TI - Assessment of the clinical status of primary root carious lesions using an enzymic assay. AB - The microflora of root carious lesions (n = 151) and sound root surfaces (n = 30) in 22 institutionalized, older patients was investigated using a standardized method of sampling. Material was removed using a sterile excavator and the numbers of bacteria in each sample were determined using conventional culturing techniques and by rapid (2 h) fluorogenic enzyme assay. Correlation between bacterial counts and enzyme assay result was 0.873 (p < 0.001). The numbers of bacteria and fluorogenic enzyme assay values were significantly (p < 0.001) greater from soft lesions than from leathery lesions while hard lesions and sound root surfaces had significantly (p < 0.001) lower values than the other lesion types and were not different from each other. A similar trend was apparent when these values were correlated with treatment needs. The fluorogenic enzyme assay may provide a rapid, objective measure of root caries severity which might be used in the monitoring and comparison of treatment protocols. PMID- 8448777 TI - Radiovisiographic diagnosis of dental caries: initial comparison of basic mode videoprints with bitewing radiography. AB - Radiovisiography (RVG) is a commercially available, dental radiographic digital imaging system which is claimed to rival conventional techniques in terms of decreased radiation dose and the production of instantaneous images. The aim of this study was to compare in vitro the sensitivities and specificities derived from three examiners using conventional bitewing radiographic film (D and E speed) with those achieved by the same examiners using basic mode RVG bitewing videoprints of occlusal and approximal caries. Videoprints were used in this study, as they are the principal method of archiving radiovisiographic images, unless a separate compatible personal computer is used. The histological appearance of the subsequently sectioned teeth was used as the validating criterion. The in vitro results of basic mode RVG suggest that for occlusal caries, overall the sensitivity and specificity of RVG videoprints are similar to those of bitewing radiography. For approximal caries, the specificity of RVG videoprints was similar to that of bitewing radiography, but the sensitivity was slightly lower. Further work using the different modes available and electronically modified images is indicated. PMID- 8448779 TI - Trends in dental caries in 12-year-old children in Ljubljana, Slovenia. AB - In Slovenia accurate data on caries trends have not been available. Therefore, in this epidemiological study the caries status of 12-year-old children was compared over time for the years 1970, 1985 and 1991. Each survey comprised examinations of around 150 children of similar socio-economic background, attending the same three schools in Ljubljana. Dental examinations in each survey were carried out by the same examiner. The mean number of decayed, missing and filled teeth (DMFT) decreased from 8.15 in 1970 to 2.96 in 1991 (64%) and the mean number of decayed, missing and filled surfaces (DMFS) decreased from 17.25 in 1970 to 5.11 in 1991 (70%). The mean number of carious surfaces per tooth dropped from 2.12 in 1970 to 1.72 in 1991. The greatest decline occurred on the approximal surfaces (92%), whereas the involvement of occlusal, lingual and buccal surfaces decreased by about 50-60%. The difference between mean DMFT in 1970 and 1985 was statistically significant. Similar differences were found for DMFS (p < 0.05). In the future, a further reduction in caries level may be expected following the introduction of fissure sealing for the preschool and schoolchild population. PMID- 8448778 TI - Dental fluorosis, dental caries and fluoride exposure among 7-year-olds. AB - Mild dental fluorosis is frequently linked to fluoridated water, but discretionary fluoride sources may also be important. The aim of this study was to record age of weaning and fluoride exposure from water, toothpaste and supplements, and to relate these to the presence of caries and fluorosis in children born in 1983. In Perth (Western Australia) 14 school classes were selected. The 350 children (mean age 7.5 years) ultimately included gave fluoride exposure data for the period birth to 4 years of age. Caries (DMFT, WHO criteria, no radiographs) and dental fluorosis (TF index, dry permanent incisors) were registered clinically. Most (89%) children had lived at least 2.5 years in a fluoridated area. Supplement use was minimal and unrelated to caries or fluorosis. Mean age of weaning of those who had been breast-fed was 7.7 months; by 9 months, 74% had been weaned. Eighty-five percent liked toothpaste, 60.7% had swallowed it, and the mean age of starting to use it was 1.5 (SD 0.96) years. Caries prevalence was 0.1 and mean DMFT was 0.13. The prevalence of fluorosis was 0.48; 63% of fluorosis was TF score 1. Residence in a fluoridated area for > or = 2.5 of the first 4 years of life had an odds ratio (OR) of 4.9 for fluorosis. Weaning before 9 months of age, swallowing toothpaste and liking toothpaste were also statistically significant risk factors. Major risk factors for more severe fluorosis (TF > or = 2) were early weaning and swallowing toothpaste (ORs 2.77 and 2.64, respectively). Residence in a fluoridated area (OR 2.2) was not a statistically significant risk factor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448780 TI - Relationships between birefringence and mineral content in artificial caries lesions of enamel. AB - The microradiographic mineral content and birefringence in water and Thoulet's solution were measured at selected points in sections of caries-like lesions. Birefringence was not related to mineral content in sound superficial enamel immersed in Thoulet's solution or in the lesion body immersed in water. For the surface layer of the lesion, birefringence in water could be used to obtain qualitative information about mineral content. For the lesion body, birefringence in Thoulet's solution was linearly related to mineral content and can be used to estimate the latter with a standard error of about 7 vol%. The intrinsic birefringence for the lesion body was estimated as -34.5 (+/- 2.3) x 10(-4); This value may also be valid for other parts of the lesion. From consideration of ionic sizes, it is argued that Thoulet's solution cannot necessarily penetrate all enamel pores accessible to water. It appeared that there is a progressive fall in the content of pores inaccessible to Thoulet's solution in the surface layer of the lesion as demineralisation increases. PMID- 8448781 TI - Exteroceptive suppression of temporalis muscle activity: findings in headache. AB - Exteroceptive suppression of temporalis muscle activity was proposed by Schoenen and co-workers in 1987 as a tool in headache diagnosis and research. Their finding of a decreased or abolished second silent period (ES2) in chronic tension type headache sufferers has been confirmed by several independent laboratories during the last five years. Temporalis silent periods have also been studied in various other types of headaches. Their modulation by neuropsychological factors and pharmacological agents has also been investigated as well as their retest reliability. The pathophysiological concept of muscle contraction in tension-type headache has been challenged by studies using temporalis silent periods. The exteroceptive suppression of temporalis muscle activity points unequivocally towards a central pathogenetic mechanism, although it remains unclear whether the abnormalities of temporalis ES2 represent the primary dysfunction or a secondary phenomenon in chronic tension-type headache. PMID- 8448782 TI - Exteroceptive suppression of temporalis muscle activity: perspectives in headache and pain research. AB - The paper describes possible future applications of the exteroceptive suppression (ES) of temporalis muscle activity in headache and pain research. ES is examined as a method for investigating the pathophysiology of pain mechanisms, for assisting clinical diagnosis, and for evaluating therapeutic effects. ES is one of the newest methods in headache research which permits an objective analysis of head pain as well as pain mechanisms and accordingly has an important future in headache research. PMID- 8448783 TI - The nociceptive flexion reflex as a tool for exploring pain control systems in headache and other pain syndromes. AB - The authors review the neural pathways mediating nociceptive flexion reflexes, the method for analyzing these reflexes in human beings, and available data on their modulation by supraspinal, opioid as well as serotonergic systems. They present results of studies of the biceps femoris flexion reflex (RIII) in pain syndromes and various types of headache. Nociceptive flexor reflexes appear to be interesting for studying the pathophysiology of head pain mechanisms and possibly for evaluating analgesic treatment. PMID- 8448784 TI - Contingent negative variation: methods and potential interest in headache. AB - Contingent negative variation (CNV) is an event-related slow cerebral potential which has been found abnormal in migraine. Its methodology is described. Contrary to other neurophysiological techniques, CNV needs special equipment and expertise. On average, CNV amplitude is increased and its habituation is lacking in migraine without aura between attacks, but not in migraine with aura. The sensitivity of CNV as a diagnostic tool is low, but its specificity is high. CNV amplitude normalizes after treatment with beta-blockers. The CNV abnormalities in migraine might be due to hyperreactivity of central catecholaminergic pathways. PMID- 8448785 TI - Exteroceptive suppression of temporalis muscle activity: methodological and physiological aspects. AB - In recent years studies of the suppression of EMG activity in temporalis muscle induced by stimulation in the trigeminal territory have opened new perspectives in headache research. The various methods that have been used in different laboratories are reviewed and some of the physiological modulations of temporalis exteroceptive suppression are described. Among different methods of recording, averaging 10 full-wave rectified EMG responses produces results with acceptable variability and discomfort. In order to obtain maximal responses the intensity of the stimulation should reach at least 20 mA. To avoid habituation of the second temporalis exteroceptive suppression period (ES2), the stimulation frequency has to be at 0.1 Hz or below. The level of voluntary contraction is not a critical variable as long as it reaches 50% of maximum. Some physiological variations of temporalis suppression are well documented. In females, ES2 is shorter during menstruation than at mid-cycle and correlated with the estradiol/progesterone ratio in plasma. Conditioning temporalis ES2 by a preceding peripheral stimulus markedly reduces its duration, which is partly reversible by naloxone. Various pharmacological agents are able to modify temporalis ES2: its duration is increased by 5-HT1 antagonists, but decreased by 5-HT uptake blockers; contradictory results have been obtained with acetylsalicylic acid. These results suggest that inhibitory brain-stem interneurons mediating temporalis ES2 are inhibited by serotonergic afferents, probably from the raphe magnus nucleus, and that the latter receives an excitatory input from the periaqueductal gray matter and other limbic structures, in part via opioid receptors. PMID- 8448786 TI - Contingent negative variation--findings and perspectives in migraine. AB - Contingent negative variation (CNV) is a negative cerebral potential which is related to attention and arousal. CNV occurs during an experimental situation in which stimuli and responses are serially organized. Between attacks migraine patients have on average higher negative amplitudes compared to healthy controls or patients with tension-type headache. Successful treatment with beta-blocking agents decreases CNV amplitudes. In spite of encouraging findings in neurological disorders, CNV is not widely used. In this review some possible reasons for this are pointed out. PMID- 8448787 TI - Is increased amplitude of contingent negative variation in migraine due to cortical hyperactivity or to reduced habituation? AB - The aim of this study was to compare the habituation kinetics of contingent negative variation (CNV) between 12 migraineurs without aura and matched healthy controls. CNV was studied with a 3 sec interval between the warning stimulus (WS) and the imperative stimulus (IS). The data from (a) the total interval (WS-IS), (b) early component, and (c) late component were analyzed. During successive trials the habituation kinetics were determined using regression analysis. On CNV averaged over 32 trials, migraine patients had a significantly higher negativity in the total interval compared to controls. When sequential blocks of four trials were analyzed, the most significant finding in migraineurs was lack of habituation of the early CNV component. The present study indicates that a delayed habituation, rather than a general increased cortical activity, is responsible for the CNV abnormalities in migraine without aura. We suggest that migraineurs between attacks not only have a cortical hyperexcitability, but also a lack of cortical inhibition causing delayed habituation. PMID- 8448788 TI - Contingent negative variation in childhood migraine. AB - Adult migraineurs without aura have an increased amplitude of the Contingent Negative Variation (CNV) between attacks. Given the potential diagnostic importance of this finding and the difficulties associated with diagnosing migraine in childhood it seemed important to assess CNV in children suffering from this disorder. Ninety-seven children aged between 8 and 14 years were recruited. Forty-two suffered from migraine, 34 from tension-type headache. Twenty-one healthy controls were also studied. CNV was recorded from Fz, Cz and Pz referenced to linked earlobes during 20 trials consisting of two tones of moderate intensity with an interstimulus interval (ISI) of 4 sec and an intertrial interval (ITI) of 10 to 14 sec. The second tone of each trial required a button press. EOG was recorded from the left eye. The 10 CNV responses with the least EOG artefact were selected and averaged. Children with migraine had a highly significantly more negative mean CNV amplitude at all three electrode sites than children with tension-type headache and also a more pronounced Post Imperative-Negative-Variation (PINV). Migrainous children differed from controls only at Cz (ISI). There was also a highly significant increase of mean CNV amplitude and PINV at all three electrode sites in the control group compared to the tension headache group. PMID- 8448789 TI - Topographic EEG mapping methods. AB - After almost 40 years of research on EEG computer analysis, present clinical applications of this method remain limited. At the present time, EEG mapping is suited primarily for research. Despite the pitfalls of an uncritical application of EEG mapping, progress in clinical research made possible by EEG mapping techniques has been considerable. Some problems of data acquisition, display and statistical analysis are discussed in this paper. For headache research examination of the activated EEG, especially with photic stimulation, has greater diagnostic importance than mapping under resting conditions. PMID- 8448790 TI - Computerized EEG topography in childhood migraine between and during attacks. AB - Topographic EEG mapping was performed in 58 migrainous children (mean age: 12.9 years; 39 without, 19 with aura) between attacks. Ten children were also recorded during an attack with visual aura. Between attacks there were no significant differences between migraineurs and age-matched controls. During visual aura a decrease in occipital alpha power contralateral to the affected hemifield was found in all patients. This was followed by a bilateral frontal increase in delta power, and, during the headache, by an increased delta activity in posterior temporal and occipital electrode sites. The possible brain mechanisms underlying these EEG changes are discussed. PMID- 8448791 TI - Topographic EEG mapping in childhood headaches. AB - The clinical distinction between migraine without aura and tension headache is more difficult in young children than it is in adults. The objective of this study was to examine the usefulness of topographic EEG mapping, as one method among other diagnostic techniques, for establishing a diagnosis. The clinical diagnosis of tension headache and migraine in children between 6 and 15 years of age was established according to criteria of the International Headache Society classification. Children with migraine and tension headache were examined during and between attacks. EEG mapping showed lateralized parietal diminution of alpha power more frequently during an attack of migraine than during tension headache, which regressed between attacks. Compared to other methods, such as visual evoked potentials, EEG mapping may have the advantage of helping to diagnose each single headache, which could be useful in patients with combined headaches. PMID- 8448792 TI - Comparison of shortening with timing of wall motion in detecting regional abnormalities of the left ventricle in coronary disease. AB - Clinical observations suggest that ischemic myocardium may demonstrate delayed wall motion while absolute shortening remains normal. Wall motion timing and percent shortening were examined in 25 patients (7 normal, 18 coronary disease) with 35 mm biplane left ventriculograms and coronary arteriography. Mean age was 63 +/- 2.4 years. Of 17 males and 8 females, 13 had 3 vessel, 4 had 2 vessel, and 1 had 1 vessel disease. Left ventricular regions were analyzed using the Coronary Artery Surgery Study nomenclature and quantitative computer-based analysis as well as visual based qualitative analysis. Regional percent shortening and ejection fraction were calculated from end systolic and end diastolic frames. Regional shortening times were related to global ejection time from 30 frame/sec, frame by frame analysis. Feeder arteries were stenosed ( > 70%) in 135 of 225 left ventricular regions analyzed. Computer detection (shortening and timing) identified 97/225 as abnormal (p < 0.01 vs. feeder artery stenosis) while physicians identified 79/225 as abnormal (p < 0.01 vs. feeder artery stenosis). Of the 97 computer detected abnormal regions, shortening alone detected 47, timing alone detected 39, and 11 showed both abnormalities. Timing analysis increased detection of wall motion abnormalities from 58/225 (26%) to 97/225 (43%) (p < 0.001). Timing abnormalities were noted more (92%) in basal segments, while shortening abnormalities dominated (88%) in apical segments (p < 0.001). Use of temporal measurements in wall motion analysis significantly increases the likelihood of detecting abnormal left ventricular regional wall motion when compared to shortening measurements alone. PMID- 8448793 TI - Effects of intracoronary injection of acetylcholine on coronary collateral circulation. AB - To clarify the effect of intracoronary injection of acetylcholine on coronary collateral circulation, acetylcholine (20 and 50 micrograms) was injected directly into the donor artery of 5 patients with rest angina who had angiographically demonstrable collateral channels. Coronary spasm was defined as severe vasoconstriction (> or = 90% of luminal diameter) with chest pain and/or ischemic ST-segment changes. The intracoronary injection of acetylcholine induced spasm in all the 5 patients. The site of spasm was collateral vessels in 3, and the recipient coronary artery in 2 of the 5 patients. The spasm resolved spontaneously without administration of nitroglycerin. The contralateral intracoronary injection of acetylcholine also induced diffuse coronary spasm in 4 patients. These findings indicate that collateral vessels and recipient coronary arteries of the collateral circulation are susceptible to acetylcholine. Impaired relaxation and vasospastic responses to acetylcholine presumably due to endothelial dysfunction in the collateral and recipient coronary vessels may explain, at least in part, myocardial ischemia in patients with a well-developed collateral circulation. PMID- 8448794 TI - Percutaneous transvenous mitral commissurotomy using the Inoue balloon catheter. AB - Since its inception in 1982, percutaneous transvenous mitral commissurotomy (PTMC) with the Inoue balloon catheter has gained increasingly wide use internationally. The procedure is technically successful in over 90% of patients, and the long-term durability of commissurotomy is excellent in those with pliable mitral valve leaflets and minimally deformed submitral apparatus. PTMC offers an alternative to patients previously not considered candidates for surgery, where no alternative had existed in the past. After transseptal puncture, PTMC using the Inoue balloon can be accomplished easily in the majority of patients. In comparison to double balloon mitral valvotomy, the postdilatation valve area is similar, the incidence of mitral regurgitation is not different, and the fluoroscopic and procedure time are markedly shorter. While patients with little valve deformity are excellent candidates for this procedure, and those not considered candidates for surgical therapy are also easily defined, selection of patients for balloon dilatation among those with significant valve deformity who are otherwise candidates for valve replacement therapy remains a challenging problem. PMID- 8448795 TI - Balloon mitral valvotomy by using the Twin-AT catheter: immediate results and complications in 110 patients. AB - Balloon mitral valvotomy, using a new Twin AT catheter (two balloons attached side by side over one shaft), was performed in 110 consecutive cases. The age of the patients ranged from 19-78 yr (mean 46 +/- 15). From a total of 94 females and 16 males, 23 of the patients (22%) had mitral valve calcification, 47 patients (46%) had atrial fibrillation, and 39 patients (37%) had mitral regurgitation (< +2). Twenty patients (18%) presented with restenosis following surgical commissurotomy. Total catheterization time was 101 +/- 26 min and the duration of the valvotomy procedure was 37 +/- 21 min in these cases. For the entire population, there was a significant reduction in mitral valve gradient (15 +/- 6 to 4.8 +/- 2.6 mmHg, p < .001), an increase in mitral valve area (MVA) (1.1 +/- 0.3 to 2.35 +/- 0.7 cm2, p < .001), and a decrease in mean pulmonary arterial pressure (31 +/- 12 to 26 +/- 11, p < .002) after the balloon mitral valvotomy. Sixteen patients (14%) developed significant left to right shunt, and in 22 patients (20%) mitral regurgitation increased moderately but without resulting in emergency valve replacement. There was one incidence of embolic episode and one pericardial tamponade. Adequate hemodynamic results (MVA > 1.5 cm2 and % increase in MVA > or = 50%) without major complications were obtained in 99 cases. In 9 patients with severely diseased valve (2 previous commissurotomy, one restenosis after balloon valvotomy), or small left ventricular cavity, insufficient results were obtained by the Twin-AT catheter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448796 TI - Prograde double balloon dilation of congenital aortic valve stenosis: a case report. AB - A new method for prograde balloon dilation of severe congenital aortic valve stenosis is described. Two TEGwire balloons were used prograde through bilateral femoral venous sheaths. Excellent hemodynamic results were achieved, without the need for retrograde left heart catheterization and femoral arterial sheath placement. PMID- 8448797 TI - Pulmonary balloon valvotomy for severe valvular pulmonic stenosis with congestive heart failure beyond infancy. AB - Isolated valvular pulmonic stenosis (PS) in association with tricuspid regurgitation and congestive heart failure (CHF) is rarely encountered after infancy, and there is very little information available regarding the application of pulmonary balloon valvotomy (PBV) for this subset of patients. Since 1985, 10 patients (5 males, 5 females; mean age: 12.4 +/- 7.5 years, range 4-25 years) underwent PBV for severe valvular PS with CHF in our institution. All patients had associated tricuspid regurgitation and cardiomegaly. Before PBV, the mean peak systolic gradient across the right ventricular outflow was 131 +/- 36 mmHg and the mean right atrial pressure was 14.4 +/- 5.4 mmHg. Specific modifications in the PBV technique included the sequential use of progressively larger balloon catheters and the use of an extra stiff guidewire to support the dilatation assembly. One patient underwent PBV via the right internal jugular vein. Problems encountered during PBV included hypotension and bradycardia (2 patients) and respiratory arrest, which was transient in one patient, and prolonged and eventually fatal in one patient. A successful outcome was achieved in 8 patients (4 of these required 2 PBV attempts) with a final residual gradient of 40 mmHg or less, mean 28 +/- 7; range: 21-38 mmHg) and complete resolution of CHF. One patient has had no significant change in gradients and awaits repeat dilatation. Patients with isolated severe valvular PS with TR and CHF represent a relatively high risk group for PBV. A successful outcome is, however, feasible if a carefully planned and cautious approach is used. PMID- 8448798 TI - Percutaneous double balloon valvuloplasty for stenosis of porcine bioprostheses in the tricuspid valve position: a report of 2 cases. AB - The feasibility and results of percutaneous double balloon valvuloplasty were evaluated in 2 patients with stenosis of porcine bioprostheses in the tricuspid valve position. The procedures were performed with a Trefoil 3 x 10 and a 15 mm balloon. Long inflations (4 and 3 minutes) were well tolerated. A significant immediate increase in the valve area, without significant valvular regurgitation, was achieved in both cases, from 0.65 to 1.15 cm2 in case 1 and from 0.9 to 1.65 cm2 in case 2. Both patients required valve replacement during the follow-up, at 14 and 21 months. There was no restenosis, but echocardiography showed right atrial thrombosis in case 1. Progressive restenosis with peripheral edema and increase of the mean doppler gradient occurred in case 2. The procedure is feasible, safe, and well tolerated. It provides significant immediate hemodynamic improvement, but it should be considered as a palliative technique since a normal valve area can not usually be obtained and a restenosis is likely to occur at midterm follow-up. PMID- 8448799 TI - Cortical blindness after cardiac catheterization: effect of rechallenge with dye. AB - Transient cortical blindness (CB) is a rare complication of dye usage during cardiac catheterization, percutaneous transluminal coronary angioplasty (PTCA) or directed coronary atherectomy (DCA), and is limited to few case reports. In this paper, we are describing three such cases of CB who, upon reexposure to dye during subsequent cardiac catheterization, did not develop CB. To our knowledge, the consequences of reexposure of these patients to dye has not been described in literature. PMID- 8448800 TI - Contained rupture following percutaneous transluminal coronary angioplasty: long term outcome. AB - Coronary artery aneurysm formation can occur as a complication of balloon angioplasty. We present a case of a contained rupture of the left circumflex artery following angioplasty which resulted in an unusual pseudoaneurysm on angiography at 3-year follow-up. PMID- 8448801 TI - Examination of the effects of hemodynamic and pharmacologic interventions on coronary collateral flow in a patient during cardiac catheterization. AB - The vasomotor response of native human collateral vessels to pharmacologic or hemodynamic vasodilatory stimuli is not well known. We describe a case where retrograde collateral flow velocity was measured both at baseline and following selected hemodynamic and pharmacologic interventions. This index case represents the first in a series of potential human physiologic studies designed to address questions pertaining to control of collateral blood supply in humans. PMID- 8448802 TI - Transcatheter closure of residual atrial septal defect following cardiac transplantation. AB - An almost 3-year-old boy had a residual atrial septal defect after cardiac transplantation. The patient was symptomatic and had arrhythmia and cardiac enlargement. An atrial septal defect occlusion device was employed to close the communication with excellent results. Transcatheter occlusion enabled the patient to avoid further surgery and did not interfere with follow-up endomyocardial biopsies. PMID- 8448803 TI - Interpretation of cardiac pathophysiology from pressure waveform analysis: multivalvular regurgitant lesions. AB - Multivalvular regurgitant lesions may have a common etiology, such as an underlying connective tissue disorder, Marfan's disease or cardiomyopathy. Careful collection of routine simultaneous left and right heart hemodynamics will document the individual valvular lesions. Combined echocardiography and angiographic data will further support the interpretation of the hemodynamic waveforms. Clinical decisions for valve repair or replacement will be based on the severity of associated lesions, myocardial function and other patient specific characteristics [9] indicating the acceptable limits of surgical risk. PMID- 8448804 TI - Effects of ultrasound energy on thrombi in vitro. AB - Ultrasonic energy may be used for dissolution of venous or arterial thrombi. However, its effects may depend on the mode of ultrasonic vibration and on the length of the probe. We investigated the in vitro effects of an ultrasonic angioplasty device coupled with a 130 cm-long flexible titanium probe, with an incorporated automatic optimal frequency of resonance scanning function and continuous mode of emission. Sixteen clots were treated of which eight were whole blood and eight cell-free. In each of these groups, four were treated in association with streptokinase and four by ultrasound alone. The ages of the clots in these subgroups of four were 1, 3, 7, and 15 days. All thrombi were dissolved in 6 min or less (3'15" +/- 1'35") at a mean optimal frequency of resonance of 19,444 Hz. Ninety-six percent of the debris were less than 10 mu. Fewer than 1% of the particulates were larger than 100 mu. These large particulates were observed in disrupted whole blood clots and were almost non existent in disrupted cell-free clots. They were very fragile. Clot dissolution was not speeded by adding streptokinase to ultrasound. Ultrasound did not induce D-Dimer production, and its effect was most likely to be due to cavitation. Ultrasound energy could represent an advance for thrombotic vascular occlusion therapy, provided that more flexible probes can be devised. PMID- 8448805 TI - Selective coronary angiography via antegrade venous route in congenital cyanotic heart disease. AB - An antegrade venous technique was utilised to perform selective coronary angiography in cyanotic infants and children. The procedure was successful in 88% (37/42) cases and excellent quality angiograms were recorded. The importance of proper catheter selection and details of the technique are discussed. PMID- 8448806 TI - ACT measurement. PMID- 8448807 TI - No thank you kindly. PMID- 8448808 TI - Effects of an ionic versus a nonionic low osmolar contrast agent on the thrombotic complications of coronary angioplasty. AB - An increasing body of evidence suggests that the potential for thrombotic complications is greater with nonionic than with ionic contrast agents. This is a particularly important consideration in the highly thrombogenic setting of percutaneous transluminal coronary angioplasty (PTCA). To explore this issue further, 500 consecutive patients undergoing PTCA were prospectively randomized to receive the low osmolality ionic ioxaglate or the nonionic agent iohexol. The number of acute thrombotic in-laboratory events was significantly less in the ioxaglate than in the iohexol group (8 versus 18; P < 0.05), but there was no significant difference between the 2 groups as regards the number of out-of laboratory acute rethrombotic events. With multivariate analysis, use of the nonionic agent rather than the ionic agent emerged as an independent predictor of acute in-laboratory rethrombosis. These data suggest that, in the performance of PTCA, an ionic, rather than a nonionic, should be the preferred contrast agent. PMID- 8448809 TI - Particular ability of cytochrome P-450 CYP3A to reduce glyceryl trinitrate in rat liver microsomes: subsequent formation of nitric oxide. AB - Glyceryl trinitrate was denitrated in rat hepatic subcellular fractions, with formation of glyceryl dinitrates and glyceryl mononitrates. Among differently treated-rat liver microsomes, the highest microsomal activity was obtained under anaerobic conditions with microsomal preparations from dexamethasone-treated rats and NADPH. The reaction was inhibited by O2, CO, miconazole, dihydroergotamine and troleandomycin showing that it was catalyzed by cytochrome P-450 CYP3A isoforms. The formation of a transient cytochrome P-450 Fe(II)-NO complex during this reaction was shown by visible spectroscopy. The cytosolic activity was shown to be dependent on glutathione and glutathione transferase and was not inhibited by dioxygen. In the hepatic 9000 x g supernatant containing both NADPH and cytochrome P-450 and glutathione and glutathione transferase, the cytochrome P 450-dependent reaction accounts for 30-40% of the total denitration activity observed under anaerobic conditions, using 100 microM GTN. PMID- 8448810 TI - Biological and toxicological consequences of quinone methide formation. AB - Quinone methides are a class of reactive, electrophilic compounds which are capable of alkylating cellular macromolecules. They are formed during xenobiotic biotransformation reactions and are hypothesized to mediate the toxicity of a large number of quinone antitumor drugs as well as several alkylphenols. In addition, oxidation of specific endogenous alkylphenols (e.g. coniferyl alcohol) and alkylcatechols (e.g. N-acetyldopamine, dopa) to quinone methides plays an important role in the synthesis of several complex plant and animal polymers, including lignin, cuticle and melanin. The role of quinone methides in these various processes is reviewed. PMID- 8448811 TI - Differential effects of extracellular calcium on lipid peroxidation dependent (ethacrynic acid and allyl alcohol) and lipid peroxidation independent (disulfiram)-induced cytotoxicity in normal and vitamin E-deficient rat hepatocytes. AB - Hepatocytes have been isolated from normal and vitamin E-deficient rats in which the hepatic vitamin E level was less than 6% that of controls. The hypothesis was tested that extracellular calcium ameliorates chemical-induced cell killing because it decreases the extent of vitamin E loss induced by oxidative stress: such a retarding effect of calcium on cytotoxicity should be lost in hepatocytes from vitamin E-deficient rats. In normal hepatocytes, allyl alcohol and ethacrynic acid induced oxidative stress as indicated by GSH depletion, lipid peroxidation and cell death. Extracellular calcium retarded the induction of lipid peroxidation and cell death without affecting the GSH depletion. In vitamin E-deficient cells, extracellular calcium had lost its protective effect on ethacrynic acid- and allyl-alcohol induced cytotoxicity; it did not affect the GSH depletion and subsequent induction of lipid peroxidation and cell death by ethacrynic acid. However, in vitamin E-deficient hepatocytes, extracellular calcium even potentiated the cytotoxicity of allyl alcohol; under those conditions it also increased GSH loss. Neither in normal, nor in vitamin E deficient hepatocytes, extracellular calcium had an effect on disulfiram-induced cytotoxicity, i.e. cell death in the absence of lipid peroxidation. These results support the hypothesis that the protecting effect of extracellular calcium on cytotoxicity, associated with lipid peroxidation in normal hepatocytes, is mediated by its protection against intracellular vitamin E loss. PMID- 8448812 TI - Synthesis and antihypertensive activities of new 1,4-dihydropyridine derivatives containing a nitrooxy moiety at the 3-ester position. AB - The synthesis of a new series of dihydropyridines containing a nitrooxy moiety at the 3-ester position is described. The antihypertensive activity of the compounds was examined and compared with that of nifedipine; some of them were relatively potent. The structure-activity relationship is also discussed. PMID- 8448813 TI - Synthesis and structure-activity study of protease inhibitors. V. Chemical modification of 6-amidino-2-naphthyl 4-guanidinobenzoate. AB - By developing 6-amidino-2-naphthyl 4-guanidinobenzoate (I, FUT-175) as a basic structure, its various derivatives were synthesized and their inhibitory activities on trypsin, plasmin, kallikrein, thrombin, C1r and C1s as well as on complement-mediated hemolysis were examined. The protective effect of these compounds on complement-mediated Forssman shock was also examined in guinea pigs. 6-Amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino]-benzoate (41, FUT 187) was found to be a suitable compound for oral administration with anti complement activity superior to that of compound I. PMID- 8448814 TI - Studies on cerebral protective agents. III. Novel 4-arylpyrimidine derivatives with anti-anoxic and anti-lipid peroxidation activities. (3). AB - Novel 4-arylpyrimidine derivatives, bearing an amino moiety in the C-5 or C-6 position of the pyrimidine ring, were synthesized and tested for anti-anoxic (AA) activity in mice. Among them, 6,7-dihydro-6-[2-(dimethylamino)-ethyl]-4-(3 nitrophenyl)-2-phenyl-5H- pyrrolo[3,4-d]pyrimidine-5-one (2a, FR 75469) and 6 methyl-5-(4-methyl-piperazin-1-ylmethyl)-4-(3-nitrophenyl) - 2-phenylpyrimidine (4c, FR 72707) had comparable potency 10-100 mg/kg, i.p. and p.o.) to that of 6 methyl-5-(4-methylpiperazin-1-ylcarbonyl)-4-(3-nitrophenyl )-2-phenylpyrimidine (FK 360). These were also effective on anti-lipid peroxidation (ALP) assay and arachidonate-induced cerebral edema in rats. Structure-activity relationship in regard to AA activity of this series of compounds are discussed. Three dimensional molecular electrostatic potentials (3D-MEP) around the nitrogenous basic moiety of FK 360 and 5-acetyl-6-(2-dimethylaminoethyl)-4-(3-nitrophenyl)-2- phenylpyrimidine (5f) were compared, and both electrostatic potential maps were similar. PMID- 8448815 TI - Synthesis and biological activity of 3'-hydroxy-5'-aminobenzoxazinorifamycin derivatives. AB - As a part of our studies on the syntheses of benzoxazinorifamycin derivatives, 3' hydroxy-5'-aminobenzoxazinorifamycin derivatives were synthesized, and tested for their antimicrobial activities. The antimicrobial activities of these compounds against gram-positive and gram-negative bacteria were almost identical to those of rifampicin (RFP) and rifabutain (RFB), however, antimicrobial activities against Mycobacterium tuberculosis were superior to RFP, while being similar to RFB. 3'-Hydroxy-5'-(4-alkyl-1-piperazinyl)benzoxazinorifamycin derivatives also had in vitro potent activities against Mycobacterium avium complex (MAC). Their minimal inhibitory concentration values against MAC were 2-256 times greater than RFP and RFB. Their in vivo efficacies against M. tuberculosis and MAC, after oral administration to mice, were superior to RFP and RFB, except for RFB against M. tuberculosis activity in vivo. Although they were absorbed from the gastrointestinal tract, their plasma levels were lower than that of RFP. Among these 5'-(4-alkyl-1-piperazinyl) derivatives, 3'-hydroxy-5'-(4-isobutyl-1 piperazinyl)benzoxazinorifamycin, compound 19 (KRM-1648), was selected as the most promising and its preliminary pharmacokinetic characteristics in mice were investigated. Compound 19 was distributed much more in tissues, especially in spleen and lung, than in plasma and had a long elimination time from tissues. PMID- 8448816 TI - Studies on cerebral protective agents. IV. Synthesis of novel 4-arylpyridine and 4-arylpyridazine derivatives with anti-anoxic activity. AB - In a search for new cerebral protective agents, a series of 4-(3- or 4 nitrophenyl)-6-phenylpyridines (or pyridazines) and 2-(3-nitrophenyl)-6 phenylpyridines, possessing an amino moiety at the C-3 position of the pyridine (or pyridazine) ring, were synthesized through the corresponding novel 1,4 dihydro derivatives and tested for anti-anoxic (AA) activity in mice. Four compounds (2c, 2f, 3a, 4a) possessed significant AA activity at a dose of 32 mg/kg, i.p. These results suggest that four-atom linkages between the C-3 position of the pyridine (or pyridazine) ring and the nitrogenous basic moiety also seems to be a prerequisite for the expression of AA activity. PMID- 8448817 TI - Studies on cerebral protective agents. V. Novel 4-(3-nitrophenyl)pyridine and 4 (3-nitrophenyl)pyrimidine derivatives with anti-anoxic activity. AB - Novel 4-(3-nitrophenyl)pyridine and 4-(3-nitrophenyl)pyrimidine derivatives, possessing three-atom linkages between basic nitrogen and at the C-5 (or C-3) position of the pyrimidine (or pyridine) ring, were synthesized and tested for anti-anoxic (AA) activity in mice. Among them, 6-methyl-4-(3-nitrophenyl)-2 phenyl-5-(pyrrolidinomethylcarbonylamino )pyrimidin e (10f) had the most potent AA activity (3.2 mg/kg, i.p.). Three-dimensional molecular electrostatic potentials (3D-MEP0 around the nitrogenous basic moiety of 6-methyl-5-(4 methylpiperazin-1-ylcarbonyl)-4-(3-nitrophenyl )-2-phenylpyrimidin e (FK 360) and 10f were compared. The negative zone of 10f is broader and deeper and positioned somewhat differently to that of FK 360, although there is a co-occupied spacial area in part. PMID- 8448818 TI - Phytochemical studies of seeds of medicinal plants. III. Ursolic acid and oleanolic acid glycosides from seeds of Patrinia scabiosaefolia Fischer. AB - Three isomeric pairs of ursolic acid (1, 3, and 5) and oleanolic acid (2, 4, and 6) glycosides were isolated as predominant constituents from seeds of Patrinia scabiosaefolia Fischer (Valerianaceae). Based on chemical and spectral evidence, their structures were established to be 3-O-[alpha-L-rhamnopyranosyl-(1-->2) alpha-L-arabinopyranosyl] ursolic acid (1) and oleanolic acid (2), 3-O-[beta-D glucopyranosyl-(1-->3)-alpha-L-arabinopyranosyl] ursolic acid (3) and oleanolic acid (4), and 3-O-[alpha-L-rhamnopyranosyl-(1-->2)-[beta-D-glucopyranosyl- (1- >3)]-alpha-L-arabinopyranosyl] ursolic acid (5) and oleanolic acid (6), respectively. Glycosides 1, 5, and 6 are new compounds and named as patrinia glycosides A-I, B-I, and B-II, respectively. Glycoside 3 is a known but is the first naturally occurring product. Ursolic acid glycosides were first found from this plant specimen. PMID- 8448819 TI - Saussureamines A, B, C, D, and E, new anti-ulcer principles from Chinese Saussureae Radix. AB - Five new amino acid-sesquiterpene adducts, saussureamines A, B, C, D, and E, were isolated from Chinese Saussureae Radix, the dried root of Saussurea lappa CLARKE, together with a new lignan glycoside, (-)-massoniresinol 4"-O-beta-D glucopyranoside. Their structures were determined on the basis of chemical and physicochemical evidence. Among of these compounds, saussureamines A, B, C showed anti-ulcer effect on HCl/ethanol-induced lesions in rats, and saussureamine A also exhibited a inhibitory activity on stress-induced ulcer formation in mice. During the course of these studies, facile conversion from sesquiterpene having an alpha-methylene gamma-lactone function to amino acid-sesquiterpene adduct has been accomplished by means of Michael type addition reaction. PMID- 8448820 TI - Saponin and sapogenol. XLVII. On the constituents of the roots of Glycyrrhiza uralensis Fischer from northeastern China. (1). Licorice-saponins A3, B2, and C2. AB - From the air-dried root of Glycyrrhiza uralensis, collected in the northeastern part of China, ten new oleanane-type triterpene oligoglycosides were isolated together with glycyrrhizin (1) and several known flavonoids. Among the newly isolated triterpene oligoglycosides, the chemical structures of licorice-saponin A3 (2), licorice-saponin B2 (3), and licorice-saponin C2 (4) have been determined, on the basis of chemical and physicochemical evidence, to be expressed as 30-O-beta-D-glucopyranosylglycyrrhizin, 11-deoxo-glycyrrhizin, and 3 O-[beta-D-glucuronpyranosyl(1-->2)-beta-D-glucuronpyranosyl++ +]oleana- 11,13(18) dien-30-oic acid, respectively. During the course of these studies, facile conversions from glycyrrhizin (1) to licorice-saponins A3 (2), B2 (3), and C2 (4) have been accomplished. PMID- 8448821 TI - Prostatic cancer: an overview. PMID- 8448822 TI - Rodent models for targeted oncogenesis of the prostate gland. AB - Currently, prostate cancer ranks as the most frequent non-skin malignancy detected in males. Yet, of the major human cancers, it remains one of the least understood in terms of its molecular and genetic basis. Research on prostate cancer has been limited by the paucity of tissues available for study. Much of the tissue obtained through surgery for localized prostate cancer will be required for pathological staging and grading. The more aggressive forms of prostate cancer are usually detected subsequent to metastatic involvement at which point there is little reason to surgically remove the prostate tumor(s). A final complication is the propensity of prostate cancer to metastasize to the bone, a site extremely difficult to obtain suitable biopsies for study. Further hindering research efforts on prostate cancer is the lack of suitable animal models for study. In contrast to its frequent occurrence in humans, prostate cancer is a rare event in most other mammalian species, particularly laboratory rodents. Therefore, in order to make this disease more amenable for study, there is a growing effort to identify or develop a means to target oncogenesis to the prostate gland of rodents. As will be reviewed here, this goal is being approached with the use of 3 different methods; one that takes advantage of the unique androgenic hormone requirement for prostate growth to exaggerate the effects of carcinogens at that site and two methods (recombinant retrovirus transduction prior to organ reconstitution and transgenic targeting) that allow direct genetic manipulation of cells in the prostate gland leading to the development of prostatic malignancy. PMID- 8448823 TI - In vivo and in vitro approaches to study metastasis in human prostatic cancer. AB - Prostate cancer is the most common malignancy in American males and is second only to lung cancer as a cause of death in the United States. Clinically, radical prostatectomy offers a patient with locally contained disease an excellent chance for cure. For patients with metastatic disease, the current therapies are merely palliative. Understanding the biology of prostate cancer metastasis should facilitate the development of novel and effective therapeutic modalities. Crucial to this objective is the availability of human tumor systems in which the biology of metastasis can be studied. The present chapter will briefly assess various in vivo and in vitro approaches to study metastasis in human prostate cancer. Utilization of athymic nude mice has played an important role in maintaining human prostatic cancer cells as xenografts and has provided an opportunity to establish site-specific subpopulations of the parental cell lines for further characterization and investigation. At present, a few established cell lines have been useful for this purpose. Fresh tumor specimens, unfortunately, have shown limited ability to grow in nude mice. The recent development of novel approaches to permit the maintenance of freshly harvested prostate cancers has been encouraging. The use of reconstituted basement membrane (Matrigel) for co injection with cancer cells into the subcutaneous tissues has supported growth of biologically indolent tumors. Another approach is to administer tumor cells orthotopically into the prostate of recipient nude mice. Bone marrow metastases in nude mice have been rare in the past. Recently, three approaches have been shown to be successful in accomplishing bony metastasis with PC-3 cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448824 TI - Decreased expression of the intercellular adhesion molecule E-cadherin in prostate cancer: biological significance and clinical implications. PMID- 8448825 TI - Molecular and cellular markers for metastatic prostate cancer. PMID- 8448826 TI - Autocrine factors, type IV collagenase secretion and prostatic cancer cell invasion. AB - Motility factors play a major role in tumor cell invasion and metastases. The biochemical properties of various motility factors; the receptor mediated mechanism of action; the role of microtubules; the potential influence of oncogenes; and the influence of motility factors on type IV collagenase secretion and invasion are discussed. We report on expression of a 70 kDa motility factor, termed invasion stimulating factor (ISF), in human prostatic PC-3 sublines. Boyden chamber chemotactic assays and measurements of type IV collagenase synthesis and secretion suggest that an ISF-receptor dependent mechanism influences tumor cell invasion and protease secretion. Taken together, the evidence that autocrine motility factors play an essential role in tumor cell invasion and metastases is compelling. PMID- 8448827 TI - Cellular motility and prostatic carcinoma metastases. PMID- 8448828 TI - Symposium on out-of-laboratory testing. April 30-May 2, 1992, Ottawa, Ontario. Selected papers and capsules. PMID- 8448829 TI - Extra-laboratory immunoassays: technology for rapid analyses of tests ranging from drugs to infectious diseases. PMID- 8448830 TI - Can patient-initiated laboratory testing in drug stores, walk-in clinics, and at home be trusted? PMID- 8448831 TI - Cholesterol testing--a lifestyle focus for the nineties. PMID- 8448832 TI - Diabetes monitoring with out-of-laboratory tests. PMID- 8448833 TI - Impact of doctor's office testing on patient care. PMID- 8448834 TI - Home monitoring of anticoagulant therapy. PMID- 8448835 TI - Problems and promises for out-of-lab tests for the detection of sexually transmitted diseases. PMID- 8448836 TI - The determination of plasma or serum sialic acid. AB - Plasma or serum sialic acid has been established as a potential tumour marker. More recently it has been shown that elevated serum sialic acid is a risk factor for cardiovascular mortality. A variety of assays are available to measure serum or plasma sialic acid and are discussed in this review, along with other clinical conditions in which serum or plasma sialic acid may be of relevance. Other factors influencing serum or plasma sialic acid concentrations are also discussed. PMID- 8448837 TI - Enzymatic determination of triglyceride, free cholesterol, and total cholesterol in tissue lipid extracts. AB - Triglyceride, free cholesterol, and total cholesterol were quantified in lipid extracts of liver and thoracic aorta from nonhuman primates using commercially available enzymatic reagents. Lipids were solubilized in water by the addition of Triton X-100. Results of the enzymatic assays compared favorably with chemical assays of lipids separated by thin-layer chromatography. In addition to saving time, the present method has the advantage of measuring each lipid class from a single sample preparation. Furthermore, the procedure has been adapted for use with microtiter plates that conserve both sample and reagent. PMID- 8448839 TI - Moving out of the laboratory: facing the challenge. PMID- 8448838 TI - Comparison of serum copper determination by colorimetric and atomic absorption spectrometric methods in seven different laboratories. The S.F.B.C. (Societe Francaise de Biologie Clinique) Trace Element Group. AB - An interlaboratory collaborative trial was conducted on the determination of serum copper using two different methods, based on colorimetry (test combination Copper, Boehringer Mannheim, Mannheim, Germany) and flame atomic absorption spectrometry (FAAS). The general performance of the colorimetric method was below that of FAAS, except for sensitivity and linear range, as assessed by detection limit (0.44 versus 1.32 mumol/L) and upper limit of linearity (150 versus 50 mumol/L). The range of the between-run CVs and the recovery of standard additions were, respectively, 2.3-11.9% and 92-127% for the colorimetric method and 1.1 6.0% and 93-101% for the FAAS method. Interferences were minimal with both methods. The two techniques correlated satisfactorily (the correlation coefficients ranged from 0.945-0.970 among laboratories) but the colorimetric assay exhibited slightly higher results than the FAAS method. Each method was transferable among laboratories. PMID- 8448840 TI - A multicenter evaluation of the Boehringer Mannheim ES 300 immunoassay system. AB - The ES 300 system, a fully automated multichannel immunoassay analyzer, was evaluated simultaneously for 9 weeks in four major centers. Precision, accuracy, carryover, comparison to in-house methods, and interferences were assessed for the following 17 tests: T4, T3, FT4, TSH, TBK, TBG, LH, FSH, prolactin, HCG, digoxin, cortisol, ferritin, IgE, insulin, AFP, and CEA. All centers reported good intra-lab and inter-lab precision. Accuracy was judged to be good based on correlation with in-house methods and recovery of target values in commercial and proficiency control materials. Linearity was evaluated for 14 analytes. Method biases were observed for T3 and insulin that were attributed to differences in standardization. No significant interferences from bilirubin, lipemia, and hemolysis were observed for all methods except insulin and AFP. Featuring random access capability, low daily maintenance, and high throughput, the ES 300 system performed well and met the stated claims of the manufacturer. PMID- 8448841 TI - Apolipoprotein(a) is present in the triglyceride-rich fraction in type IV hypertriglyceridemia. AB - This study was designed to quantify the levels of apo(a) and assess their distribution among lipoprotein fractions in type IV hypertriglyceridemia. Plasma density < 1.006 g/mL fraction (VLDL) was obtained by preparative and zonal ultracentrifugation. Apo(a) was detected by immunoblotting with anti-apo(a) antibodies of agarose gel electrophoresed lipoproteins. Apo(a) was consistently found in VLDL in 30 hypertriglyceridemic subjects, but not in 10 normolipidemic or 10 hypercholesterolemic subjects with normal triglyceride levels. Apo(a)B particle concentrations were then measured using a selective 'sandwich' ELISA with anti-apo(a) as the capture antibody and anti-apoB as the detecting antibody. The mean apo(a)B level of VLDL in six hypertriglyceridemic patients was 30% (range 1.3-50%) of the total plasma concentration. Apo(a)-containing particles of both plasma, d < 1.006 g/mL and d > 1.006 g/mL, had the same pre-beta mobility on agarose gel electrophoresis and a similar apparent molecular weight on non denaturing 2-16% gradient polyacrylamide gel electrophoresis. Fractionation of plasma by zonal ultracentrifugation confirmed the presence of a heterogeneous distribution of apo(a) in hypertriglyceridemic subjects. Apo(a) was present throughout the density range from VLDL to Lp(a). After normalization of plasma triglyceride levels with dietary fish oil, apo(a) was no longer detected in VLDL suggesting that detection of apo(a) in the plasma, d < 1.006 g/mL, density fraction is related to type IV hypertriglyceridemia. PMID- 8448842 TI - Point-of-care testing: does it really improve patient care. PMID- 8448843 TI - Role of the laboratory in meeting the needs of critical care. PMID- 8448844 TI - Is anyone regulating the regulators? PMID- 8448845 TI - Blood alcohol testing in the clinical laboratory: problems and suggested remedies. AB - Laboratory directors or others responsible for blood alcohol testing are advised to reevaluate their procedures for alcohol tests. The demand for better traffic safety has resulted in a large increase in the number of arrests for drinking and driving violations and in a concomitant increase in the litigation of alcohol related cases. My experience in the last 20 years indicates that many difficulties in the forensic aspects of these cases and many miscarriages of justice could have been reduced or even avoided if laboratories doing alcohol analyses had followed established guidelines. The most frequently encountered problems involve the physician-patient privilege ("the test was done for medical purposes only") and the fact that alcohol results were frequently reported as blood alcohol concentrations when they were, in fact, serum alcohol concentrations. Here I discuss these problems and suggest some solutions. PMID- 8448846 TI - Application of simple chromatographic methods for the diagnosis of defects in pyrimidine degradation. AB - Recent findings suggest that inborn errors of pyrimidine catabolism are less rare than generally assumed. We propose a complete set of diagnostic methods for these disorders, suitable for the clinical chemistry laboratory, and present relevant reference data. Applications of thin-layer chromatography, high-performance liquid chromatography, and conventional cation-exchange amino acid analysis lead to detection of various defects in pyrimidine degradation, including the recently described deficiencies of dihydropyrimidine dehydrogenase and dihydropyrimidinase. We also illustrate the potential of the methods to analyze for the catabolites expected to be increased in the urine of patients with ureidopropionase deficiency. Possible pitfalls in the diagnosis and ways to prevent misdiagnosis are demonstrated. The methods offer possibilities for clinical chemistry laboratories to extend their diagnostic capacity to the new area of pyrimidine degradation defects. PMID- 8448847 TI - Liposome-based flow-injection immunoassay for determining theophylline in serum. AB - We developed a method for quantitatively determining theophylline in serum, using a heterogeneous immunoassay called flow-injection immunoanalysis. The reaction involves competition between serum theophylline and theophylline-labeled liposomes. Separation occurs on a solid-phase reactor column containing immobilized antibody to theophylline incorporated in a flow-injection system. Subsequent lysis of the bound liposomes provides sensitive detection of the analyte. Effective regeneration of the immobilized antibody activity allows the reactor to be reused for hundreds of sequential samples. Comparison of the results of the flow-injection immunoassay method with results obtained with a commercially available fluorescence polarization method showed an excellent correlation. PMID- 8448848 TI - Automated assay of methylmalonic acid in serum and urine by derivatization with 1 pyrenyldiazomethane, liquid chromatography, and fluorescence detection. AB - Determination of methylmalonic acid (MMA) in serum has been established as an accurate test for the diagnosis of cobalamin deficiency. We describe here the development and performance of a liquid-chromatographic assay of MMA in blood and urine. The assay is based on our recent finding that one of the carboxylic acid moieties of some short-chain dicarboxylic acids reacts with the fluorogenic reagent 1-pyrenyldiazomethane in an aqueous medium, whereas the other remains underivatized (Anal Chem 1992; 63:315-9). The pH-dependent ionization of the free carboxylic acid group of 1-pyrenylmethyl monoesters permits retention on anion exchange columns, which are used for solid-phase extraction. The analysis is done with a cyanopropyl column coupled in series with an octadecyldimethylsilyl column. Solid-phase extraction and sample injection are carried out automatically by a Gilson ASPEC sample processor. The assay response varies linearly with MMA concentration in the range 0.1-1000 mumol/L in serum. The within-day and between day CVs are 2.8-10.9%, and the detection limit of 5 fmol injected (approximately 20 nmol/L in serum) is sufficiently low to determine MMA in serum (mean 0.187 mumol/L, SD 0.084, range 0.044-0.431, n = 44) and urine from healthy subjects. PMID- 8448849 TI - A theoretical evaluation of linearity. AB - The measure of linearity is an important part of the evaluation of a method. According to the NCCLS guidelines (Document EP6-P), results of a linearity experiment are fit to a straight line and judged linear either by visual evaluation, which is subjective, or by the lack-of-fit test. This approach depends on the precision of the method, is not necessarily conclusive, and fails to be quantitative. We define linearity as a measure of how well a first-order (linear) polynomial fits the data compared with a higher-order (nonlinear) polynomial. The major property of a linear polynomial is that the first derivative is a constant. The nonlinearity of a method can be measured by the difference between these two polynomials (first-order and higher-order) at specific values or, as an average, the root-mean difference. This approach is independent of the precision of the assay and is conclusive, quantitative, and objective. PMID- 8448850 TI - Clinical and laboratory studies of a new immunoradiometric assay of parathyroid hormone-related protein. AB - Parathyroid hormone-related protein (PTHrP) was measured in plasma by a new immunoradiometric assay (IRMA) from Nichols Institute. The assay is specific for PTHrP and shows excellent parallelism when measuring keratinocyte fluid, samples with high PTHrP content, and PTHrP-supplemented plasma. A precision profile established the assay detection limit at 0.7 pmol/L. PTHrP was unstable in plasma, but the degradation rate was patient-specific. Because delay in separation resulted in loss of PTHrP immunoreactivity, samples were collected into tubes containing protease inhibitors (aprotinin, leupeptin, pepstatin, and EDTA) and separated within 30 min. Among normal subjects, 78% had PTHrP values greater than the detection limit; the reference range established was < 0.7-2.6 pmol/L. Of patients with hypercalcemia associated with malignancy, 46% had PTHrP > 2.6 pmol/L. PTHrP was increased in patients with breast (73%), genitourinary (64%), or lung (46%) malignancy but was rarely above normal in patients with hematological (29%) or gastrointestinal (33%) malignancy. PTHrP and nephrogenous cyclic adenosine monophosphate (NcAMP) were strongly correlated (r = 0.63, P < 0.01) in 37 patients with PTHrP values greater than the detection limit, but 8 patients had PTHrP and parathyroid hormone [PTH(1-84)] values below the limit of detection with inappropriate or increased NcAMP. Five of these eight patients had small cell carcinoma of lung. These patients may have secreted a factor that is not detected by the IRMAs of PTHrP or PTH used in this study but that produces hypercalcemia by means of cAMP-mediated mechanisms. PMID- 8448851 TI - Behavior of tumor markers CA19.9, CA195, CAM43, CA242, and TPS in the diagnosis and follow-up of pancreatic cancer. AB - We compared the recently proposed tumor markers CA195, CA242, and CAM43 with a widely used antigen, CA19.9, and a circulating marker of cellular proliferation, TPS, to define their specificity, sensitivity, and cost-benefit ratio. The tumor markers were measured in 41 pancreatic carcinoma patients and in two control groups, the first comprising 19 patients with benign pancreatic diseases, the second comprising 41 healthy blood donors. Sensitivities were 79% for CA19.9, 57% for CA242, 60% for CAM43, 76% for CA195, and 98% for TPS. Specificities calculated for the group with pancreatic diseases were 60% for CA19.9, 84% for CA242, 95% for CAM43, 53% for CA195, and 22% for TPS. Specificities for the blood donor group were 100% for CA19.9, 93% for CA242, 98% for CAM43, 85% for CA195, and 88% for TPS. Positive values for the tumor markers appeared from second stage (Hermreck classification). Metastases, invasion of lymph nodes, and coupling of cancer-associated antigens did not significantly modify marker sensitivity. In pancreatic carcinoma, CA19.9 showed good sensitivity (79%) and high specificity (60-100%). In view of their own advantages (e.g., high specificity of CAM43, high sensitivity of TPS in recurrences) and limits (e.g., low sensitivity of CAM43, very low sensitivity of TPS), the other markers could be used alone or with CA19.9. Two pairs of tumor markers showed high similarity in our study: CA19.9 and CA195, and CAM43 and CA242. PMID- 8448852 TI - Evaluation of regression procedures for methods comparison studies. PMID- 8448853 TI - Rapid enzymatic analysis for human immunodeficiency virus type 1 DNA in clinical specimens. AB - A clinical procedure for rapid detection of human immunodeficiency virus type 1 (HIV-1) by DNA amplification is demonstrated. The rapid procedure reduces handling requirements and amplification time and eliminates use of radioactivity for the detection of the amplification product. Total leukocyte lysates are the amplification substrates. Two conserved regions in the HIV-1 genome are amplified by 45 cycles of a two-temperature thermal cycle and the amplification products are detected by ultraviolet light after electrophoresis on agarose gels. Twenty four specimens clinically diagnosed by detection of antibody (IgG) to HIV-1 were confirmed by the rapid DNA amplification procedure. In a blind study, 56 samples positive for HIV-1 DNA were detected in 503 individuals by the current classical polymerase chain reaction method; the same 56 positive samples were also detected by the rapid amplification protocol. No false-positive or false-negative results were obtained. The turnaround time for analysis has been reduced to < 24 h without compromising test results. PMID- 8448854 TI - New insight into the comparative power of quality-control rules that use control observations within a single analytical run. AB - The error detection characteristics of quality-control (QC) rules that use control observations within a single analytical run are investigated. Unlike the evaluation of QC rules that span multiple analytical runs, most of the fundamental results regarding the performance of QC rules applied within a single analytical run can be obtained from statistical theory, without the need for simulation studies. The case of two control observations per run is investigated for ease of graphical display, but the conclusions can be extended to more than two control observations per run. Results are summarized in a graphical format that offers many interesting insights into the relations among the various QC rules. The graphs provide heuristic support to the theoretical conclusions that no QC rule is best under all error conditions, but the multirule that combines the mean rule and a within-run standard deviation rule offers an attractive compromise. PMID- 8448855 TI - Measurement of deoxyribonuclease I activity in human tissues and body fluids by a single radial enzyme-diffusion method. AB - In the single radial enzyme-diffusion (SRED) method for assay of deoxyribonuclease I, a precisely measured volume of the enzyme solution is dispensed into a circular well in an agarose gel layer in which DNA and ethidium bromide are uniformly distributed. A circular dark zone is formed as the enzyme diffuses from the well radially into the gel and digests substrate DNA. The diameter of the dark circle of hydrolyzed DNA increases in size with time and correlates linearly with the amount of enzyme applied to the well. Thus, the SRED can be used for quantitation of deoxyribonuclease I with a limit of detection of 2 x 10(-6) unit. This corresponds to 1 pg of purified urine deoxyribonuclease I. We measured the deoxyribonuclease I activity of 17 different human tissues and body fluids from healthy donors. Urine samples showed the greatest activity, 6.0 +/- 2.2 kilo-units/g protein (mean +/- SD). Serum deoxyribonuclease I activity was 4.4 +/- 1.8 units/L. PMID- 8448856 TI - Simultaneous quantification of mannitol, 3-O-methyl glucose, and lactulose in urine by HPLC with pulsed electrochemical detection, for use in studies of intestinal permeability. AB - The percentage of an oral dose of mannitol, 3-O-methyl glucose, and lactulose excreted in urine is used in noninvasive investigation of active and passive intestinal mucosal transport. We developed a high-pressure liquid-chromatographic method involving anion exchange and pulsed electrochemical detection that allows the simultaneous determination of all three sugar probes in urine. Sample preparation is simple: diluting, mixing with internal standard (melibiose), and desalting. With use of a Dionex 250 x 40 mm Carbopac PA-1 column and elution with an isocratic mixture of 120 mmol/L NaOH and 0.5 mmol/L zinc acetate, all sugars were resolved within 10 min. The standard curve of the method is linear to the following concentrations: mannitol 125 mg/L, 3-O-methyl glucose 300 mg/L, and lactulose 40 mg/L. The minimal detectable concentration of lactulose is 0.4 mg/L. Analytical recovery of the sugars is between 89.0% and 99.5%. The precision of estimation (CV) ranges from 1.76% to 5.6% overall. Reference intervals were established from results for 28 healthy children. The method is adaptable for the study of carbohydrates at low concentrations in other biological fluids. PMID- 8448857 TI - Preparative chromatographic purification of cyclosporine metabolites. AB - Polar and primary metabolites of cyclosporin A (CsA) have successfully been isolated by a novel separation protocol. An efficient, easy-to-scale-up chromatographic adsorption/desorption operation recovers polar and primary CsA metabolite pools from large volumes of urine; purified CsA metabolites are subsequently obtained by high-resolution preparative elution chromatography of the semipurified metabolite pools. Separations performed on a semipreparative scale [with a 250 x 9.4 mm (i.d.) reversed-phase HPLC column] yielded microgram quantities of CsA metabolites at > 97% purity, as determined by fast atom bombardment mass spectrometry. These separations also yielded two previously unreported CsA metabolites, similar to AM1A but with an additional hydroxylation. The yield of metabolites was increased to several milligrams by performing the separations with a preparative-scale [250 x 21.2 mm (i.d.)] reversed-phase column. The production rate of purified primary CsA metabolites was greatly increased by performing the separation with the preparative-scale column under conditions of severe mass overloading. In a single chromatographic run, we successfully isolated 11.0 and 5.0 mg of AM1 and AM1c, respectively, at a purity of > 97%. As expected, this increase in the yield of purified metabolites was accompanied by a decrease in the overall recovery. This separation scheme enables the rapid processing of large volumes of urine for isolation of the milligram quantities of CsA metabolites necessary to assess their biological activity. The procedure is applicable to small- or large-scale metabolite isolation and provides a ready source of purified metabolites for in vitro and whole-animal studies. PMID- 8448859 TI - Monoclonal antibody-based immunoenzymometric assays of retinol-binding protein. AB - Retinol-binding protein (RBP) is a low-molecular-mass protein (21 kDa), easily filtered in renal glomeruli and very efficiently reabsorbed by the proximal convoluted tubules (PCTs). In PCT dysfunction, high concentrations of RBP are found in urine. Several methods have been used to determine RBP in serum or urine. We describe the production, selection, labeling, and utilization of anti RBP monoclonal antibodies in two- or one-step immunoenzymometric assays for the determination of RBP. The one-step assay has good precision, with within-run and between-run CVs < 6.6% and 5.9%, respectively. Comparison with radial immunodiffusion (x) showed good agreement: y = 0.068 mg/L + 0.899x (n = 24). Comparison between the one-step (y) and two-step (x) versions of the assay also showed a very good correlation: y = 212 micrograms/L + 0.910x. The one-step assay has been adopted for routine work; it detects transthyretin-bound as well as free RBP and may have clinical usefulness in evaluating the functional status of PCTs. PMID- 8448858 TI - Aberrant PO2 values in proficiency testing. AB - We prospectively determined the frequency of aberrant vials of fluorocarbon/buffer used for proficiency testing of measurements of pH, PCO2, and PO2, using 20 duplicate vials from 12 lots of fluorocarbon/buffer and two arterial blood gas analyzers in eight reference laboratories. We defined aberrant vials as vials for which both duplicate measurements differed from the mean value of repeated measurements for the specific instrument (for each lot of testing materials) by > 0.04 for pH, > 10% of the mean or 3.0 mm Hg, whichever was greater, for PCO2; or > 10% of the mean or 6 mm Hg, whichever was greater, for PO2. Four of 1620 vials (0.25%) were aberrant, all based on PO2 measurements (< 70 mm Hg); all would have failed in both American/California Thoracic Societies and College of American Pathologists proficiency programs. The average intra instrument SDs of repeated measures (range of mean values: pH, 7.181-7.631; PCO2, 12.7-65.9; PO2, 32.5-150.1) were 0.0055 for pH, 0.67 mm Hg for PCO2, and 1.65 mm Hg for PO2. Deliberate contamination of the fluorocarbon emulsion with room air, as might occur during sampling from the vial, indicated that only minor increases in PO2 (e.g., 1.0 mm Hg at PO2 of 56 mm Hg) occur when samples are aspirated. Larger increases in PO2 (mean 7.1 mm Hg at a PO2 of 66 mm Hg) occurred when the syringe samples were contaminated with room air. We conclude that isolated aberrant measurements of PO2 in blood gas proficiency testing attributable to vial contents can occur, but the frequency is very low. PMID- 8448860 TI - Relation of lipoprotein(a) in 11- to 19-year-old adolescents to parental cardiovascular heart disease. AB - We studied several risk factors in relation to parental cardiovascular heart disease: total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein (apo) A-I, apo B, and lipoprotein(a) [Lp(a)] were determined in 322 serum samples (43 from subjects with and 279 without parental cardiovascular heart disease). The distribution of Lp(a) concentrations in our young population was similar to that of other white populations, i.e., markedly skewed, with higher frequencies at low values. As compared with children whose parents did not report cardiovascular heart disease, those with affected parents had a higher mean Lp(a) (0.23 vs 0.18 g/L; P < 0.05). Moreover, 42% of the children with parental cardiovascular heart disease, but only 19% of those with no parental cardiovascular heart disease, exhibited Lp(a) values > 0.30 g/L. These results suggest not only that Lp(a) is an important risk factor for cardiovascular heart disease, but also that Lp(a) is more strongly related to the risk of cardiovascular heart disease than are HDL- and LDL-cholesterol and apo A-I and B. PMID- 8448861 TI - Cocaine and benzoylecgonine in saliva, serum, and urine. AB - We studied the feasibility of using saliva to detect cocaine and benzoylecgonine. Saliva was collected as an ultrafiltrate directly in the mouth with an osmotic device. We analyzed by immunoassay matched samples of urine, blood, and salivary ultrafiltrate from 69 patients who had used cocaine within 24 h of sample collection. Cocaine concentrations were 4.9 times higher in saliva than in serum; benzoylecgonine concentrations were 2.5 times higher in serum. Seven urine and two serum samples had undetectable concentrations of cocaine, but all 69 saliva samples were positive for the drug. For benzoylecgonine detection, all urine samples were positive and three serum and one saliva sample were negative. We also analyzed 43 samples of saliva by gas chromatography/mass spectrometry: all were positive for benzoylecgonine, whereas 40 were positive for cocaine. We conclude that simultaneous measurement of cocaine and benzoylecgonine in saliva is suitable in screening for recent cocaine use. PMID- 8448862 TI - Diagnostic evaluation of creatine kinase-2 mass and creatine kinase-3 and -2 isoform ratios in early diagnosis of acute myocardial infarction. AB - The diagnostic efficacy of creatine kinase (CK) isoforms (CK-3 and CK-2) was compared with measurement of CK-2 mass concentrations for the early diagnosis of myocardial infarction (MI). Serial serum samples drawn from 76 patients with confirmed MI and 55 non-MI patients were used for determining CK-2 mass concentrations and the MM3/MM1 (CK-3 isoforms) and MB2/MB1 (CK-2 isoforms) ratios. We compared the diagnostic utility of each by receiver-operating characteristic (ROC) curve and likelihood ratio analyses. Our results indicate that all three tests were ineffective within the first 4 h after the onset of chest pain. All three were most effective at 4-18 h after onset, but both CK-3 and CK-2 isoform ratios were less effective than CK-2 mass concentrations in the next 6-h period (18-24 h). In the critical time between 3 and 6 h, the diagnostic performance of all three was comparable. PMID- 8448863 TI - Clinical measurement of serum amiodarone and desethylamiodarone by using solid phase extraction followed by HPLC with a high-carbon reversed-phase column. AB - We describe a rapid, simple HPLC method routinely used in our clinical laboratory for determining amiodarone and its metabolite desethylamiodarone. These compounds are released from serum proteins by pretreatment with an acidic solution and then extracted onto a C2 reversed-phase clean-up column. After elution from the extraction column, the compounds are separated and quantified by HPLC with a C18 reversed-phase column and spectrophotometric detection. The standard curves for the drug and metabolite are linear up to 20.0 mg/L, with a lower limit of detection of 0.16 mg/L. The CVs for intra-assay precision were 5.0% at 0.58 mg/L and 2.9% at 5.96 mg/L; for inter-assay precision, they were 9.6% at 0.52 mg/L and 6.1% at 2.09 mg/L. Lipemia, hemoglobin, and bilirubin up to 300 mg/L do not interfere with this assay. None of > 550 cardiac patients' samples tested contained a compound that interferes with this assay. PMID- 8448864 TI - Automated enzymatic determination of sodium in serum. AB - An automated method based on the principles of flow-injection analysis is proposed for the enzymatic determination of sodium ion in serum. The method relies on the activation of beta-galactosidase by the analyte. The features of the proposed method include linear range between 1 and 1700 mumol/L, a sampling rate of 50 samples/h, a sample volume of 50 microL, and the absence of interferences from species usually present in serum. The results obtained were consistent with those provided by widely used methods such as those based on flame spectrometry and direct potentiometry with ion-selective electrodes. PMID- 8448865 TI - Rate nephelometric assay of serum lipoprotein(a). AB - This nephelometric assay of serum lipoprotein(a) [Lp(a)] is characterized by the use of a specific antibody to generate a high rate of light-scatter formation and the elimination of nonspecific reactions from serum samples by diluting samples in phosphate-buffered saline containing polymer enhancer polyethylene glycol (PEG), 40 g/L, and detergent before the assay. We reacted 100 microL of sixfold diluted serum in 500 microL of buffer containing PEG with 42 microL of pure polyclonal rabbit antiserum (Dakopatts) directed against human Lp(a) and monitored the reaction by rate nephelometry with the Array Protein System nephelometer (Beckman). The standard curve for the reaction was linear in the Lp(a) range 10-1280 mg/L; antigen excess occurred between 1300 and 1400 mg/L. Calibration was performed with serial dilutions of a standard serum. Precision studies showed within-run and between-run CVs of < 2.1% and 6.9%, respectively. The nephelometric results (y) for 100 serum samples were highly correlated with those obtained by radial immunodiffusion (x) calibrated with the same materials: y = 1.07 (+/- 0.03) x - 16.2 (+/- 8.1) mg/L (r = 0.974, P < 0.001). Storing serum for 3 weeks at 4 degrees C or 3 months at -80 degrees C did not affect the results. PMID- 8448866 TI - Endogenous antibodies that interfere with thyroxine fluorescence polarization assay but not with radioimmunoassay or EMIT. AB - We have identified an individual whose thyroxine (T4) concentration was undetectable with Abbott's fluorescence polarization immunoassay (FPIA) but within the reference range by radioimmunoassay or EMIT (Syva). The patient's thyrotropin, triiodothyronine, and T-uptake values were within the normal range. The T4 concentration measured by FPIA increased to normal when the immunoglobulin fraction was selectively removed from the serum. When the patient's immunoglobulin fraction was added to normal serum, the T4 content of the normal serum measured by FPIA became falsely low. The patient's antibody interfered with the T4 FPIA by binding to the fluorescein-T4 conjugate. The T-uptake was less affected by the patient's serum because of the low affinity of the patient's antibody to fluorescein-T4 (K = 3.5 x 10(8) L/mol). The patient's immunoglobulin bound preferentially to fluorescein-T4, in comparison with binding to fluorescein or T4 alone. We conclude that the patient's immunoglobulin bound to an epitope unique to the fluorescein-conjugated T4. PMID- 8448867 TI - Rapid determination of erythrocyte pyruvate kinase activity. AB - We report a new potentiometric method for determining pyruvate kinase (PK). Enzymatic activity is measured by monitoring the change in pH produced in the reaction buffer under International Committee for Standardization in Haematology (ICSH) standardized assay conditions, and the lactate dehydrogenase reaction is automatically subtracted in each measuring cycle. The analysis, performed at 37 degrees C, requires a 10-microL sample (isolated erythrocytes or whole blood) and is completed in 2.5 min. The intra-assay CV is < 4% (PK between 3 and 35 U/g Hb); the interassay CV is 4.0% (PK 15 U/g Hb); results are linear from 3 to 30 U/g Hb. A good correlation with the ICSH reference method (x) was found: y = 1.011x - 0.05; n = 32; r = 0.9939; Sylx = 0.75 (units: U/g Hb). The reference intervals of the PK activity in isolated erythrocytes (RBC-PK) were estimated in 89 normal subjects. We found that women possess a higher RBC-PK than do men (P < 0.0001) and that the biological variability (CVb) of RBC-PK is 13.5%. Applications of the proposed method to the hematological routine are reported. PMID- 8448868 TI - Low-molecular-mass proteinuria as a marker of proximal renal tubular dysfunction in normo- and microalbuminuric non-insulin-dependent diabetic subjects. AB - We determined the urinary excretion, expressed as the protein/creatinine ratio (morning urines), of albumin (a marker of glomerular dysfunction) and retinol binding protein (RBP; a low-molecular-mass protein marker of tubular proteinuria) in 102 non-insulin-dependent diabetic patients. There was a statistically significant (P < 0.0001) correlation (rho = 0.38) between the urinary excretion values of the two proteins. The population could be divided into four subgroups: 32 with normal excretion values, 15 with above-normal urinary excretion of RBP, 24 with above-normal urinary excretion of albumin, and 31 patients with above normal urinary excretion of both proteins. No patients had above-normal serum creatinine concentrations or above-normal serum RBP concentrations. This seems to exclude "tubular overflow proteinuria" as the cause of the increased urinary excretion of RBP seen in some patients with non-insulin-dependent diabetes. Our data suggest the presence of a state of proximal tubular dysfunction in these patients. PMID- 8448869 TI - Testosterone concentration is increased in whole saliva, but not in ultrafiltrate, after toothbrushing. AB - The concentration of testosterone in whole saliva is significantly increased (by 9%) after toothbrushing. In ultrafiltrates of saliva collected at the same time as the whole saliva, testosterone concentrations after toothbrushing were unchanged. In 88% of the 162 whole-saliva specimens, but not in the ultrafiltrates, we also measured higher hemoglobin concentrations after toothbrushing. We conclude that the increase of testosterone in whole saliva after toothbrushing can be attributed to a protein-bound fraction. For analytes that are bound to serum proteins, salivary measurements can give spurious results. This problem can be avoided by using as a diagnostic medium an ultrafiltrate of saliva collected directly in the mouth. PMID- 8448870 TI - Modified method for determining carcinoembryonic antigen in the presence of human anti-murine antibodies. AB - The increasing use of monoclonal antibodies (MAbs) for disease diagnosis and therapy has created a class of patients at risk for systematic error in clinical testing due to interference by human anti-murine antibodies (HAMA). HAMA interference is often difficult to detect and can cause either an increase or a decrease in apparent concentrations of antigen present. We undertook a clinical study to test a HAMA-resistant enzyme immunoassay (EIA) format for carcinoembryonic antigen (CEA) determination. Using the Food and Drug Administration-approved CEA-EIA Monoclonal One-Step Assay (Abbott) with the addition of an acid/heat extraction of patients' specimens, we found that the resulting CEA values accurately reflected the patients' status. We demonstrated that the acid/heat-extracted specimens yield linear dilution curves and show analytical recoveries of added CEA in the range of 76-123% in HAMA-positive specimens and 86-103% in HAMA-negative specimens. The correlation of CEA values in extracted vs unextracted specimens from 184 patients and control subjects was 0.9963. The CEA detection limit of the assay was 1.6 micrograms/L for the extracted samples. PMID- 8448871 TI - Determination of vitamin D status by radioimmunoassay with an 125I-labeled tracer. AB - We report here the first radioimmunoassay for a vitamin D metabolite utilizing a radioiodinated tracer. Antibodies were generated in a goat immunized with the vitamin D analog 23, 24, 25, 26, 27-pentanor-C(22)-carboxylic acid of vitamin D, coupled directly with bovine serum albumin. The 125I-labeled tracer was prepared by reacting a 3-amino-propyl derivative of vitamin D-C(22)-amide with Bolton Hunter reagent. The primary antiserum, used at a 15,000-fold final dilution, cross-reacted equally with all cholecalciferol and ergocalciferol metabolites tested except 1,25-dihydroxycalciferol metabolites and the parent calciferols; the antiserum did not cross-react with dihydrotachysterol. Calibrators were prepared in vitamin D-stripped human serum. 25-Hydroxycholecalciferol was quantitatively extracted from serum or plasma (50 microL) with acetonitrile. The assay consists of a 90-min incubation at room temperature with primary antiserum, followed by a 20-min incubation with a second antiserum and separation of bound from free fractions by centrifugation. The detection limit of the assay was 2.8 micrograms/L for 25-hydroxycholecalciferol. Results with the present assay compared well with those from a liquid-chromatographic procedure involving specific ultraviolet detection of 25-hydroxycalciferol in plasma. PMID- 8448872 TI - How and how long to store urine samples before albumin radioimmunoassay: a practical response. AB - We used three study protocols to check the dependence of albumin stability, measured by an RIA, on different temperatures, durations, and materials (i.e., assay tubes) of urine storage. Albumin values obtained for samples stored in three types of assay tubes (glass, polystyrene, and polypropylene) throughout the 2 months of the first (prospective) protocol were superimposable. The 24-h storage of six urine samples at room temperature or at 4 degrees C, as well as 72 h storage at 4 degrees C, did not affect the albumin measurement by RIA. After 2 months of storage of these same six urine samples at -20 degrees C, there was still no albumin decrease. A significant albumin decrease occurred (a mean of approximately 5% per year, throughout the range of albumin concentrations tested) when samples stored at -20 degrees C were reassayed by RIA after > or = 2 years (second protocol, retrospective). Finally, 3 of 21 (14.3%) urine pools stored at 20 degrees C for various periods (4-21 months) showed a significant albumin loss after storage; the time of storage as well the decrement rates of these 3 pools differed from each other (third protocol, retrospective). Short- and medium-term (2-6 months) freezing of urine samples at -20 degrees C does not significantly affect the stability of immunoreactive albumin. For longer preservation periods, storage of urine samples at -70 degrees C may be preferable. PMID- 8448873 TI - Ion-chromatographic determination of plasma oxalate reexamined. AB - This new procedure for determining oxalic acid in plasma is based on sample deproteinization with hydrochloric acid and acetonitrile and subsequent ion chromatographic assay of the neutralized supernate. Sample pretreatment produces very clean samples, which ensures long column life. Mean analytical recovery of oxalate (5.0-10.0 mumol/L) added to plasma samples averaged 98.6 +/- 6.2%; imprecision (CV) was 5.2% (at 2.2 mumol/L) and the detection limit was 0.5 mumol/L at a signal-to-noise ratio of 5:1. Ascorbate to oxalate conversion was < 0.2%, indicating that the procedure is free from ascorbate interference. Plasma oxalate concentrations, measured in samples from 31 healthy persons, ranged from 0.8 to 3.4 mumol/L (mean 1.89, SD 0.75 mumol/L), which agrees with results from indirect radioisotopic dilution methods. PMID- 8448874 TI - High-molecular-mass alkaline phosphatase as a tumor marker for colorectal cancer: comparison of two test methods. AB - We measured high-molecular-mass alkaline phosphatase (HiMwALP) in serum samples from patients with colorectal cancer by polyacrylamide gel electrophoresis (PAGE) and by column chromatography on diethylaminoethyl (DEAE)-cellulose. Determination of carcinoembryonic antigen (CEA) by an enzyme immunoassay, a frequently used cancer assessment method, was used for comparison. We studied patients with primary colorectal cancer (n = 72), using others with hemorrhoids (n = 38) for a comparison group. HiMwALP activities twice those of pooled normal sera were adopted as cutoff values. The diagnostic sensitivity of the PAGE method for 72 colorectal cancer patients was 63% vs 36% for the DEAE method and 50% for the CEA method. The diagnostic specificities of the PAGE, DEAE, and CEA methods were 89%, 79%, and 95%, respectively. Using both HiMwALP (PAGE method) and CEA for the detection of primary colorectal cancer increased the sensitivity to 72% but decreased specificity to 87%. PMID- 8448875 TI - Equivalent discrimination among states of thyroid function by immunochemiluminimetric and immunoradiometric determination of thyrotropin. AB - New immunochemiluminometric assays (ICMA) of thyrotropin (TSH) have been reported to facilitate the diagnosis of hyperthyroidism. To compare the accuracy of ICMA TSH with that of a conventional immunoradiometric assay (IRMA-TSH), we examined 115 consecutive patients of a thyroid outpatient clinic. On the basis of complete thyroid-function testing, including thyroliberin tests, the untreated patients (n = 89) were subclinically hyperthyroid (n = 21), subclinically hypothyroid (n = 13), or euthyroid (n = 55). The receiver-operating characteristic (ROC) curve, used for comparing the TSH values obtained by these two methods, was shifted to the left for the IRMA-TSH. The area under the curve was greater for IRMA-TSH than for ICMA-TSH (0.984 vs 0.869, respectively), which suggests equal or better clinical performance of IRMA-TSH vs ICMA-TSH in discriminating between hyperthyroidism and euthyroidism. Both assays displayed similar clinical sensitivity/specificity for evaluating thyroid function in hypothyroid and treated patients. We conclude that the ICMA-TSH tested is not more accurate than an IRMA in distinguishing between hyperthyroidism and euthyroidism. PMID- 8448876 TI - Squamous cell carcinoma antigen in patients with cirrhosis. PMID- 8448877 TI - Mefenamic acid prevents assessment of drug abuse with EMIT assays. PMID- 8448878 TI - Polymerase chain reaction detection of a highly polymorphic VNTR segment in intron 1 of the human p53 gene. PMID- 8448879 TI - Circulating forms of B-type natriuretic peptide after acute myocardial infarction. PMID- 8448880 TI - Time-resolved fluoroimmunoassay of beta 2-microglobulin in serum and cerebrospinal fluid. PMID- 8448881 TI - Addition of sucrose avoids effect of lyophilization on determinations of lipoprotein(a) in serum. PMID- 8448882 TI - Relationship of T-uptake and thyroxine in hypo- and hyperthyroid patients. PMID- 8448883 TI - Continuing medical education. PMID- 8448884 TI - The patterns and treatment of recurrence following radiotherapy for carcinoma of the oral cavity. AB - In many centres carcinoma of the oral cavity, if relatively early, is treated by irradiation. The present study includes 186 patients treated in this manner. The primary recurrence rate for previously untreated patients was 34% and was not significantly affected by host or tumour factors. The 5-year survival for the 144 previously untreated patients was 65%, and salvage surgery offered a 35% chance of cure. Survival was reduced in patients aged 60 years and over (P < 0.02). The recurrence rate in cervical lymph nodes following radiotherapy was 38% and was more likely to occur for primary sites in the tongue and floor of mouth (P < 0.01). The five-year survival rate after nodal recurrences was 31% and was predicted only by the presence of extracapsular rupture (P < 0.01). One-third of patients had died of causes other than the primary tumour at 5 years and one third had died of the original tumour. The rest of the patients are alive and well, only 7% having had a major resection. We feel that the present policy has optimum cure rate whilst saving most patients from major surgery. PMID- 8448885 TI - Correlation of subjective sensation of nasal patency with nasal inspiratory peak flow rate. AB - To determine the relationship between subjective sensation of nasal patency and objective measurement of nasal inspiratory peak flow rate, a longitudinal study was conducted using healthy volunteers. Five healthy medical practitioners, one woman and 4 men, aged 24-34 years, made daily subjective estimations of their sensation of nasal patency on a 10-cm visual analogue scale. This was followed immediately by measurements of nasal inspiratory peak flow rate using a Youlten meter, repeated on at least 25 days per subject. Correlation coefficient and regression lines for subjective nasal patency on nasal inspiratory peak flow rate were calculated. One hundred and sixty nine sets of observations were made, range 25-44 per subject. Each subject showed strong evidence (P < 0.01) of positive correlation between subjective nasal patency score and nasal inspiratory peak flow rate. There was strong evidence (P < 0.001) that different regression lines are needed for different subjects, but no evidence that the lines are not parallel. Subjective sensation of nasal patency is strongly correlated with objective nasal patency, as measured by peak inspiratory flow rate. This relationship varies between individuals. Measurement of nasal inspiratory peak flow rate may be a valuable objective test of nasal patency, and is quick and simple to perform. PMID- 8448886 TI - The role of CT imaging in the management of chronic suppurative otitis media. AB - CT imaging of the temporal bone is highly predictive of the presence of cholesteatoma but its value in the routine management of cholesteatoma has not been assessed. We aimed to establish the indications for CT imaging in CSOM by a prospective study of patients suspected of having cholesteatoma. The patients were assessed clinically and a management plan chosen; this was later adjusted, if indicated, on the basis of radiological findings. Surgical findings were recorded and correlation with CT appearances evaluated. Twenty patients completed the study. CT altered the management plan in 10 and was considered helpful in a further 6. We recommend its routine use in children, medically unfit patients, only or better hearing ears, patients in whom the tympanic membrane cannot be adequately visualized, patients who have had previous mastoid surgery whose operative records are available and patients with intratemporal or intracranial complications of disease. PMID- 8448887 TI - Dry powder inhalation of budesonide in allergic rhinitis. AB - Topical steroids are known to be effective in allergic inflammatory airway diseases. However, progress in the treatment of these diseases has also called for the use of unadulterated drugs, without lubricants and preservatives. Rhinocort Turbuhaler, a multi-dose inhaler containing budesonide as a pure powder, is a newly developed device without any carrier gas, preservatives or lubricants. The efficacy and tolerance of this product were evaluated in 60 patients with birch pollen rhinitis. After a run-in period of 1 week the patients received once daily for 4 weeks either budesonide pure powder (400 micrograms) or placebo in a double-blind randomized fashion. Assessment of efficacy was made by comparing scores for different nasal and eye symptoms. The additional use of antihistamine tablets was assessed. In 22 of the patients nasal peak inspiratory flow rate was measured before and after 1 week of treatment. Budesonide was significantly more effective than placebo in controlling the nasal symptoms (P values ranging from 0.011-0.045). The use of antihistamine tablets was significantly lower in the budesonide group (P = 0.012). The nasal inspiratory flow rate was increased after 1 week of treatment in the budesonide treated group of patients as compared with placebo (P = 0.007). No differences were observed between the groups with regard to eye symptoms or adverse effects. The results show that budesonide delivered from a dry powder inhaler is an effective and well tolerated treatment of seasonal allergic rhinitis. PMID- 8448888 TI - Malignant melanoma of the nasal cavity and paranasal sinuses. AB - Malignant melanoma affecting the nasal cavity and paranasal sinuses is a rare condition with a poor prognosis. The Head and Neck Oncology Clinic at the University Hospital Nottingham has treated 16 patients in an 8-year-period. Twelve patients were treated with primary radical surgery and salvage radiotherapy was used for 7 patients with local recurrence. This resulted in tumour shrinkage in 4 patients. Eight patients treated surgically, have died of systemic spread. Four are currently alive, although 2 have local disease. PMID- 8448889 TI - Implications of tumour in resection margins following surgical treatment of squamous cell carcinoma of the head and neck. AB - Presence of tumour at the resection margin following primary surgical treatment for squamous cell carcinoma of the head and neck is thought to adversely affect prognosis. To confirm this we performed a review of 478 patients treated by primary surgery for squamous cell carcinoma of the head and neck and sub-divided them into those exhibiting positive margins and those with negative margins following resection. Uni-variate and multi-variate statistical methods were used to analyse survival figures and a variety of parameters associated with the presence of positive resection margins. We found 5-year survival was decreased if resection margins were found to be positive (P < 0.025). The presence of positive resection margins was also significantly associated with time to tumour recurrence (P < 0.001) and survival with nodal recurrence (P < 0.001). Other factors which were significantly associated with survival using Cox's multi variate analysis were site of tumour (P < 0.005), nodal extracapsular rupture (P < 0.05), histology (P < 0.05) and pathological T-stage (P < 0.05). Uni-variate analysis revealed no significant associations between the presence of positive margins and the patient's age, sex, tumour site, degree of tumour differentiation, and nodal status, though using multiple logistic regression, the general condition of the patient (P < 0.01) and the tumour site P < 0.05) were significantly related. The results support the concept that every effort should be made to obtain negative resection margins when undertaking primary ablative surgery for squamous cell carcinoma of the head and neck. PMID- 8448890 TI - Oncogenes and ENT: a review of the molecular biological advances in squamous cell carcinoma of the head and neck. PMID- 8448891 TI - Dominant maxillary artery as a cause of failure in maxillary artery ligation for posterior epistaxis. AB - Ligation of the maxillary artery is a logical and effective method for the arrest of severe uncontrollable posterior epistaxis. The failure rates for arrest of haemorrhage are given in the literature as 10-13%. In our centre, over the last 9 years, 23 patients have undergone maxillary artery ligation to control epistaxis without a failure. Bilateral maxillary artery ligation was carried out whenever the maxillary artery of the bleeding side was found to be of small diameter. To investigate whether there is an asymmetry in the size of the maxillary arteries we performed 13 cadaveric dissections. In 6 of the cadavers one maxillary artery was significantly larger than the other. This fact has hitherto not been observed by otolaryngologists or anatomists. Failure to arrest haemorrhage may have resulted from ligation of the non-dominant maxillary artery with consequent opening of cross-anastomoses from the dominant side. PMID- 8448892 TI - The otological profile of a cohort of Dutch 7.5-8-year-olds. AB - The otological characteristics of a birth cohort of 7.5-8-year-old Dutch children are reported. Questionnaire information was available for 1004 children, while otomicroscopic, tympanometric and pure-tone audiometric data were available for 946 children. Twenty-nine per cent of the children had been treated surgically for various ENT diseases. Fifty-five per cent of the children had normal tympanic membranes, 19% mild abnormalities, and 26% moderate to severe abnormalities. At this age the prevalence of bilateral otitis media with effusion (OME), as shown by a type B tympanogram was 2.5%, while that of unilateral OME was 7%. A pure tone average hearing level of > or = 15 dB in the better-hearing ear was found in 4% of the children. The presence of OME was associated with a mean hearing loss of 20 dB. This study shows that structural and functional middle-ear abnormalities are highly prevalent in Dutch school children. PMID- 8448893 TI - Foreign body aspiration in children. The diagnostic value of signs, symptoms and pre-operative examination. AB - One hundred and fifteen patients, between 6 months and 12 years of age, had bronchoscopy on suspicion of foreign body aspiration. The histories of these patients were studied to examine the diagnostic value of signs, symptoms and examinations, and to determine the time that passed between aspiration and removal of the foreign body. The sensitivity of the symptoms choking and coughing was fairly high (81 and 78%), but the specificity was poor. The sensitivity of a chest radiograph was 82%, the specificity 44%. The sensitivity of radiographs on inspiration and expiration was 80%, the specificity 55%. The patients had been referred with the initial diagnosis foreign body aspiration (80), pneumonia (34), or subglottic laryngitis (1). In 85 patients a foreign body was identified and extracted. The other 30 patients had respiratory tract infections. The initial diagnosis of foreign body aspiration was correct in 61 out of 85 patients. In these cases, the period between aspiration and extraction of the foreign body was a mean 6 days, compared with 55 days, if the initial diagnosis was pneumonia or sub-glottic laryngitis. We conclude that the diagnosis of foreign body aspiration is too often missed, and that, apart from bronchoscopy, diagnostic tools are of little value. PMID- 8448894 TI - Errors in the assessment of tympanic membrane perforations. AB - It is commonly stated that operative closure of large perforations of the tympanic membrane is less successful than closure of small perforations. Few authors mention the exact size of the perforations studied, and fewer still give their method of measuring perforations. We describe a photographic method of assessing the size of perforations relative to the total drumhead, measuring them with a computerized digitizing pad. Thirteen temporal bones were selected at random. Perforations of different sizes, shapes and at different sites were fashioned in the tympanic membranes. These were assessed by clinicians of all grades, who were asked to draw the perforations and give estimates of the perforation size as a percentage of the total drumhead. Visual estimates and drawings were compared with a photographic objective method. Gross errors (some in excess of 100%) were apparent in both estimates and drawings. There was a highly significant statistical difference between the objective method and visual estimates and drawings (P < 0.001). Greater clinical experience was not correlated with better performance in estimating the size of perforations. PMID- 8448895 TI - Elevated levels of the p53 tumour suppressor protein in the basal layer of recurrent laryngeal papillomas. AB - Using immunocytochemical techniques, recurrent laryngeal papillomas from six adult patients were studied. The p53 tumour suppressor gene protein was detected in the basal epithelial cells in papillomas from all six patients. None was detected in normal epithelium. Elevated levels of p53 protein are usually indicative of its inactivation either by point mutation or by complexing with tumour virus proteins. PMID- 8448896 TI - Epidermal growth factor receptors and oestrogen receptors in the head and neck. AB - We report a pilot study of the levels of epidermal growth factor receptors (EGFR) in normal and neoplastic tissues of the head and neck. Specimens from 20 consecutive patients undergoing major head and neck surgery showed that squamous cell carcinomas had detectable but widely varying levels of EGFR. EGFR expression was greater in normal salivary gland tissue than in benign salivary neoplasms. Oestrogen receptors were not detected in clinically significant amounts in any of the tumours assayed. PMID- 8448897 TI - Nasal capnography in children: automated analysis provides a measure of obstruction during sleep. AB - A detailed analysis was made of nasal capnograms obtained from sleeping children with differing degrees of sleep-induced respiratory obstruction, the severe form being known as obstructive sleep apnoea. Clinical observations of these children were compared with analyses of nasal capnography data. During periods when the degree of obstruction was consistent throughout the first hour of sleep, the means and coefficients of variation of several parameters, derived from the capnograms were calculated. The coefficients of variation showed a close relationship to the degree of obstruction. In comparison, measures of end-tidal carbon dioxide concentration proved to be a very insensitive index of the degree of obstruction. The conclusion is that the usefulness of nasal capnography in predicting and grading obstruction can easily be extended by the use of statistical measures of dispersion and that this concept warrants further work. PMID- 8448898 TI - Familial thyroglossal duct cyst. AB - Thyroglossal duct cysts are common congenital abnormalities or developmental field defects, usually detected in early childhood. Despite their frequent occurrence, familial patterns are rare. We report on two new families with thyroglossal duct cysts. In the first family three siblings were involved, while in the second one, father and son were affected. This trait may be autosomal recessive or possibly multifactorial, as the first family would indicate, and also autosomal dominant, as the second family would suggest. PMID- 8448899 TI - Geneticists approach ethics: an international survey. AB - Fletcher, Berg and Tranoy (1985) proposed that medical geneticists around the world would benefit from collective reflection on their preferred approaches to the most frequent of the difficult moral choices in practical genetics. In 1985 86, Wertz & Fletcher undertook a survey of geneticists' views in 19 nations. Results were widely disseminated. In this paper, the authors describe a new survey that they are conducting in 37 nations. PMID- 8448900 TI - High-resolution chromosome analysis in autosomal recessive disorders: Laurence Moon-Bardet-Biedl syndrome. PMID- 8448901 TI - A preliminary trial of couple screening for cystic fibrosis: designing an appropriate information leaflet. AB - An information leaflet, inviting participation in an antenatal screening trial for cystic fibrosis, was sent to 388 couples together with the pregnant woman's first clinic appointment. The leaflet pointed out that couples would be treated as a unit and that further action would be taken only if both partners were found to carry mutant alleles. Participants and non-participants were also asked to fill in a questionnaire eliciting their views on the leaflet. Three hundred and twelve (80%) questionnaires were returned and 253 (65%) couples elected to be screened. More than 90% of respondents found the leaflet easy to understand, although about 10% wanted more information on cystic fibrosis. The main reason for entering the trial was to avoid the birth of an affected child, and the main reason for non-entry was opposition to termination of pregnancy. There was little anxiety about the prospect of being screened. However, more than a third of couples mis-identified their risk of both carrying a CF gene, despite the figure of 1 in 600 being explicitly stated in the leaflet. PMID- 8448903 TI - Intrafamilial variation in Leber hereditary optic neuropathy revealed by direct mutation analysis. AB - Leber hereditary optic neuropathy (LHON) has been associated with a mitochondrial mutation at position 11,778 in the ND4 gene in about 50% of families. Individuals from six Swedish families with LHON were investigated for the presence of this mutation using allele-specific oligonucleotides and a sensitive chemoluminescent detection system. The point mutation was seen in mitochondrial DNA extracted from leukocytes in five families, four of which showed a homoplasmic pattern. One family showed a heteroplasmic pattern and one family was negative for the mutation. Six adults without impaired vision from three LHON families were detected as carriers with a degree of mutated mitochondrial DNA similar to that in affected relatives. The results show that the penetrance of LHON varies remarkably among carriers of the 11,778 mutation within families. We conclude that the prognosis for carriers should be stated cautiously when interpreting results from mutation analysis of mitochondrial DNA in leukocytes. PMID- 8448902 TI - Attitudes of Dutch general practitioners towards presymptomatic DNA-testing for Huntington disease. AB - The attitudes of 1020 Dutch GP's towards presymptomatic and prenatal testing for Huntington disease (HD) were studied by means of a postal questionnaire. The questionnaire contained questions about: approval of presymptomatic DNA-testing, informing individuals at-risk who do not request predictive testing, referral to a clinical genetics center, and opinions about different strategies of informing and supporting individuals at-risk. The response rate was 62%. More than two thirds of the GP's considered post-test counselling and support as their responsibility. Twenty-six per cent were of the opinion that the test results should be disclosed by the GP. Fifty-nine per cent of GP's who had an individual at-risk in their practice were familiar with the test. The attitudes of GP's towards giving support and giving test results were independent of familiarity with the test and the incidence of HD-patients or at-risk individuals in the practice. Although GP's were willing to play an important role in presymptomatic DNA-testing procedures, there is a risk that they might underestimate the difficulties in communicating genetic information and the psychosocial effects of DNA-testing. Hence, we favor the premise that extensive pretest counselling and test disclosure should remain the prime responsibility of the clinical geneticist. Increasing involvement of GP's should, however, be encouraged and combined with appropriate postgraduate education about predictive DNA-testing in general. PMID- 8448904 TI - Hyperkeratosis-hyperpigmentation syndrome: a confirmative case. AB - A 22-year-old female showing hyperpigmented spots and mild palmoplantar hyperkeratosis as leading features is presented. The diagnosis of Hyperkeratosis hyperpigmentation syndrome, previously described by our group as an autosomal dominant trait, was unmistakable, thus permitting the corroboration of this genodermatosis. PMID- 8448905 TI - 46,XY del(18)(q21.3q22.2) with mosaicism of r(18) and a milder form of the 18q- syndrome. AB - A mosaic karyotype: 46,XY,del(18)(q21.3q22.2)/47,XY,del(18) (q21.3q22.2)+ marker, was found in a mentally retarded male with a mild form of the 18q- syndrome and aplasia of the right thumb. By fluorescent in situ hybridisation, the marker chromosome could be identified as a ring chromosome no. 18. PMID- 8448906 TI - A case of full triploidy (69,XXX) of paternal origin with unusually long survival time. AB - Triploidy is a rare disorder in live-born children and these infants generally die within the first hours after birth. We report here on a girl with full triploidy and multiple malformations, who survived for 10 1/2 weeks. The extra set of haploid chromosomes was of paternal origin, as shown by chromosomal banding techniques. PMID- 8448907 TI - Low frequency mosaicism of normal cells in a 16-year-old girl with trisomy 18. AB - A 16-year-old girl with mosaicism of trisomy 18 has been followed from birth in our department. She had stigmata characteristic for trisomy 18. Chromosome analysis of lymphocytes showed trisomy 18 both at birth and at age 15, whereas analysis of fibroblasts at age 16 showed trisomy 18 with low frequency mosaicism of normal cells (4%). In most case reports, karyotype analyses have been performed in lymphocytes only. The low frequency mosaicism of normal cells found in fibroblasts from the present patient may raise the question of mosaicism in other long-living patients previously reported to be non-mosaic trisomy 18. The main disorders in the present patient were limited to severe mental deficiency, structural cerebral malformations and skeletal deformities, including bilateral equinovarus deformities. At birth, she had a ventricular septal defect which closed spontaneously. Frequent respiratory infections subsided after age 2. At age 7 she developed a seizure disorder. Since then, her medical condition has been stable. Even though patients with trisomy 18 rarely survive early childhood, the possibility that they may reach their teens must be kept in mind when treatment is planned. In our case, the decision not to treat her equinovarus deformities means that she cannot stand, a major problem in her everyday life. PMID- 8448909 TI - Acute adrenal crisis complicating hypertensive congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency. AB - In its classical form, congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency is characterized by hypertension and abnormal sexual development. Suppression of ACTH secretion by means of administering glucocorticoids fulfills the therapeutic goal of reducing blood pressure and decreasing androgen production. The present report describes the case of a patient suffering from congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency who developed an acute adrenal crisis, unprovoked by stress, following interruption of glucocorticoid replacement therapy. It is suggested that patients on a suppressive dose of glucocorticoids for adrenal hyperplasia are at increased risk for acute adrenal insufficiency if therapy is interrupted, and that deoxycorticosterone (DOC) in the absence of a glucocorticoid is insufficient to prevent manifestations of adrenal crisis. PMID- 8448908 TI - Oxygen radicals potentiate the genetic toxicity of tobacco-specific nitrosamines. AB - Tobacco-specific nitrosamines (TSNAs), nitrosonornicotine (NNN) and 4-(N-methyl-N nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), are metabolites of nicotine and the major carcinogens in cigarette smoke. To evaluate the effect of oxygen radicals on TSNA-induced genetic damage, MRC-5 fetal human lung cells were exposed to NNN and NNK (5 mM) and DNA single-strand breaks measured. Both NNN and NNK produced a dose-dependent increase in strand breaks up to 10 mM which was cytotoxic. In combination with enzymatically-generated oxygen radicals, strand breakage increased by approximately 50% for both NNN and NNK. Oxygen radical scavengers (superoxide dismutase, catalase, mannitol) significantly reduced the DNA damage caused by both the TSNAs and TSNAs plus oxygen radicals, suggesting that the genotoxicity is radical-mediated. Because both superoxide dismutase and catalase were protective, the hydroxyl radical may be playing an important role in the mediation of the DNA damage observed. PMID- 8448910 TI - De novo t(5p;21q) in a patient previously diagnosed as monosomy 21. AB - In situ hybridization was used to characterize an undetected chromosome translocation in a child whose metaphase chromosome analysis in peripheral blood and in skin culture revealed apparent monosomy 21. The cytogenetic study revealed 45 chromosomes, and no other structural anomalies were detected with G banding. In situ hybridization of chromosome 21-specific probes to metaphase chromosomes and reverse banding from the proband showed a de novo translocation between chromosome 5 and chromosome 21. PMID- 8448911 TI - A case of Johanson-Blizzard syndrome complicated by diabetes mellitus. AB - We report a girl with Johanson-Blizzard syndrome complicated by diabetes mellitus. She presented several characteristic malformations, such as aplasia of the alae nasi, deafness, dwarfism, absence of permanent teeth and malabsorption caused by disturbance of pancreatic exocrine function. At 11 years of age, glycosuria was detected at a routine outpatient examination. Repeated oral glucose tests showed a slowly progressive decline of insulin secretion and elevated blood glucose levels. The responsive secretion of insulin to glucagon or arginine loading was also low. The blood level of HbAlc was elevated over 9%. Based on these findings, insulin therapy was started when the patient was 13 years old. Our case suggests that diabetes mellitus might be considered as one of complications of Johanson-Blizzard syndrome. PMID- 8448912 TI - Autonomic dysfunction and the development of hypertension in patients treated with recombinant human erythropoietin (r-HuEPO). AB - Hypertension is the most common complication of r-HuEPO therapy in dialysis patients. The aim of this study was to test the hypothesis that hypertension develops in patients who fail to autoregulate adequately their hemodynamic response to correction of anemia. Twenty-five dialysis patients (17-71 yrs, 13 male, 13 CAPD) initially received r-HuEPO 50 U/kg 3 times/week intravenously or subcutaneously. Hypertension, defined as a rise in mean blood pressure (BP) of greater than 15 mmHg during therapy developed in 44% (Group 1: stable BP; Group 2: rise in BP). There was no difference in sex, age, mode of dialysis or route of administration of r-HuEPO between the groups. Before commencement and after 6-12 months of r-HuEPO therapy, assessment of the baroreflex arc was performed using the Valsalva ratio and orthostatic BP testing, sympathetic efferent nerve function was assessed by the cold pressor test and afferent parasympathetic function by the 30:15 ratio and heart rate variation (HRV). No difference was detected prior to r-HuEPO therapy between the two groups in Valsalva ratio (Group 1: 1.26 +/- 0.06 vs Group 2: 1.23 +/- 0.06, mean +/- SEM); 30:15 ratio (1.06 +/- 0.02 vs 1.03 +/- 0.01), or systolic, diastolic, mean BP or pulse rate after standing for 3 minutes or following hand immersion in ice slush. Both groups had a fall in systolic and diastolic BP (p < 0.05) and a rise in pulse rate (p < 0.05) on standing. HRV during deep respiration between the 2 groups was not different (9.6 +/- 2.3 vs 7.1 +/- 1.4 beats/minute).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448913 TI - The significance of slime-producing coagulase-negative staphylococci in CAPD peritonitis. PMID- 8448914 TI - Implantation of an implantable cardioverter-defibrillator in a patient on chronic hemodialysis. PMID- 8448915 TI - r-HuEPO treatment of anemia associated with multiple myeloma and ESRD. PMID- 8448916 TI - Depression and hormonal disturbances in chronic renal failure. PMID- 8448917 TI - Nephrotic-range proteinuria associated with atrial myxoma. PMID- 8448918 TI - Renal histology in two adult patients with type I glycogen storage disease. AB - Two adult patients with type I glycogen storage disease (I-GSD) had chronic renal disease with heavy proteinuria. Renal biopsies showed focal glomerular sclerosis, interstitial fibrosis, tubular atrophy or vacuolation, and prominent arteriosclerosis. Marked glomerular hypertrophy was demonstrated histometrically. Oil red O staining in one patient revealed numerous lipid deposits in the glomerular mesangium, tubular epithelial cells and interstitium. Electron microscopy in the other patient revealed diffuse thickening of the glomerular basement membrane (GBM) and lipid droplets within the mesangium. The glomerular hypertrophy, thickening of the GBM, and subsequent sclerosis were similar to those in insulin-dependent diabetes mellitus. These findings may explain the similarities between the natural histories of renal involvement in the two disorders. Particularly, glomerular hypertrophy may be a key step leading to glomerular sclerosis, which is the predominant finding I-GSD. Hyperlipidemia, which is commonly seen in I-GSD, may also accelerate the glomerular sclerosing process. PMID- 8448919 TI - Determination of glomerular filtration rate (GFR) on two consecutive days using inulin in a single-sample plasma clearance method. AB - Reliable estimation of the GFR is essential in nephrological practice for the early recognition and follow-up of latent or residual renal disturbance. The GFR of ten healthy volunteers on two consecutive days and of 40 patients with different renal diseases were investigated by means of a plasma slope clearance technique. After injection of 5 g/50 ml inulin solution, eight plasma samples were taken at 10, 20, 30, 40, 120, 180, 240, 300 min p.i. and analyzed with the aid of a fully enzymatic method. The results were correlated on the basis of 1- and 2-compartment models (1 CM, 2 CM) and the one-sample method (1 S), using only the plasma inulin concentration of the 240 min p.i. sample. The accuracy of the GFR data of volunteers estimated in these models was checked by comparison with the standardized agewise normal values, while for the patient group we found in terms of equations of correlation: 1. GFR (2 CM) = 4.46 + 0.763*GFR (1 S), n = 31, r = 0.985 2. GFR (2 CM) = 1.27*GFR (1 CM)0.9, n = 40, r = 0.996 3. GFR (1 CM) = 0.568*(GFR[1 S] + 5.85)1.11, derived The single-sample method using inulin is closely correlated to multi-sample methods but much more suitable for patients and staff. Therefore, it is recommended for clinical use. PMID- 8448920 TI - Long-term continuous ambulatory peritoneal dialysis. AB - Of 174 patients who entered our CAPD program, 58 received transplants, 7 were transferred to another center, one recovered satisfactory kidney function, 22 were transferred to hemodialysis, 24 to IPD, 52 died and 10 remained on CAPD for at least seven years, when this study was completed. These 10 patients (8 women and 2 men) who are described here in detail had a median age of 46 (range of 24 to 63) years at entry. Their primary renal disease was glomerulonephritis (6), polycystic kidney disease (2), nephrosclerosis (1) and Alport's disease (1). They spent 91 to 134 (average 113) months on CAPD. They had a significant (p = 0.025) increase in body weight from 54.5 +/- 2.8 kg to 59.6 +/- 3.0 kg during the first 3 years, and a decrease in ultrafiltration capacity; BUN and serum creatinine remained relatively stable. Mean total protein and serum albumin remained unchanged at 65 and 35 g/l respectively, throughout the study. There were no significant changes in the hemoglobin and lipid values. Renal osteodystrophy progressed slowly. Peritonitis rate in this group was one episode every 18.9 patient months. These 10 patients had a total of 25 catheters implanted during the study period. The average hospitalization rate was 8.76 days per patient year, 5.34 of which were for peritonitis. Of these 10 patients, one was transferred to hemodialysis, 5 died (4 of or during peritonitis, one of myocardial infarction) and 4 remained on CAPD. Our experience with these 10 patients indicates that CAPD can be carried out over long periods.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448921 TI - In vivo exposure to the currently available peritoneal dialysis fluids decreases the function of peritoneal macrophages in CAPD. AB - Previous in vitro studies have revealed that the currently available peritoneal dialysis fluids (PDF) inhibit several functions of phagocytic cells. To investigate the clinical relevance of those in vitro findings, we compared the in vivo effect of PDF pH on peritoneal macrophage (PMO) function in chronic peritoneal dialysis patients. In a randomized crossover setting, each of eight patients used exclusively PDF at pH five (D5) or pH seven (D7) on day one. The next day the patients who used D5 were switched to D7 and vice versa. Likewise the effect of glucose-mediated hypertonicity was studied in eight other patients, using PDF with 1.36% glucose (D136) or 3.86% glucose (D386). PMO were isolated from the effluents and studied for their phagocytic and killing capacity, and their ability to mount a respiratory burst (chemiluminescence response). PMO obtained after the intraperitoneal instillation of D7 were significantly better able to phagocytize both S. epidermidis (65 +/- 9 vs 37 +/- 8% uptake, p < 0.005) and E. coli (43 +/- 8 vs 25 +/- 4% uptake, p < 0.005). In addition, PMO harvested from D7 effluents revealed a significantly higher killing capacity than PMO derived from D5 effluents for S. epidermidis (60 +/- 5 vs 38 +/- 6%, p < 0.005) as well as for E. coli (51 +/- 10 vs 25 +/- 9%, p < 0.025). Moreover, PMO derived from D7 effluents mounted a significantly higher respiratory burst as compared to PMO in vivo exposed to D5 for the same time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8448922 TI - Course of left ventricular diastolic dysfunction in end-stage renal disease on long-term continuous ambulatory peritoneal dialysis. AB - To determine factors contributing to abnormal left ventricular (LV) diastolic filling in patients on long-term continuous ambulatory peritoneal dialysis (CAPD), 11 (age: 55 +/- 13 years; CAPD duration: 33 +/- 32 months) out of 42 originally studied CAPD patients were followed over 35 months with echocardiography and pulsed Doppler echocardiography. LV dimensions and systolic function remained normal. Doppler parameters indicated diastolic LV dysfunction in 9/11 patients in the initial study. Despite a significant increase in LV mass (234 +/- 54 vs. 299 +/- 65 g; p < 0.05) and a decrease in LV volume/mass ratios (0.78 +/- 0.18 vs. 0.54 +/- 0.12 ml/g; p < 0.001), no change was observed in any of the diastolic LV filling parameters such as peak early and atrial filling velocities and their ratios, atrial filling fractions and peak filling rate normalized for mitral stroke volume. Individual changes of E/A-max were inversely correlated with systolic blood pressure (p < 0.01), alterations of normalized peak filling rate were inversely correlated with serum creatinine (p < 0.01). No influence on individual changes of LV diastolic filling parameters was observed for LV volume, muscle mass, volume/mass ratios, ejection fractions, patient age, dialysis duration, and hemoglobin concentration. These findings suggest that arterial hypertension and the quality of blood purification play a central role in the development of LV diastolic dysfunction in patients on CAPD, while LV muscle mass and LV volume/mass relations have no relevant influence on changes of LV diastolic function in these patients. PMID- 8448923 TI - The effect of pilocarpine on electrodermal resistance in chronic hemodialyzed patients. AB - Electric resistance of forearm skin was examined in 40 hemodialyzed (HD) patients under resting conditions and after subjecting the skin to the action of a 10% pilocarpine gel. The results were compared with a control group of a 100 healthy volunteers. An increased skin resistance was observed before dialysis and then a significant post-dialysis fall to the normal level followed. The response to the applied pharmacological stimulus in the HD group was similar to that in the control group. The results suggest that the rise in skin resistance in patients with renal failure and the so-called uremic dry skin, are not connected with the dysfunction of the glands themselves but rather with their insufficient stimulation. PMID- 8448924 TI - Inhibition of mitochondrial respiration by furancarboxylic acid accumulated in uremic serum in its albumin-bound and non-dialyzable form. AB - 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF) accumulates markedly in uremic serum in its albumin-bound form. To determine if CMPF can be removed by newly developed dialyzers with high-flux membranes which are permeable to low molecular-weight proteins, such as beta 2-microglobulin (beta 2-MG), serum levels of CMPF were determined before and after hemodialysis using these high-flux membrane dialyzers. In addition, to determine the pathogenic role of CMPF in uremic patients, its cellular toxicity due to its effect on mitochondrial respiration was studied. The reduction rates of CMPF by hemodialysis using the dialyzers ranged from -17% to -24%, demonstrating the nondialyzability of CMPF due to its strong albumin-binding, while those of beta 2-MG ranged from 11% to 43%. CMPF inhibited ADP-stimulated oxidation of NADH-linked substrates in isolated mitochondria dose-dependently regardless of the presence of serum albumin. This inhibition was observed even at a concentration of 0.2 mM, which is comparable to the serum levels of CMPF in the hemodialysis patients. In conclusion CMPF which cannot be removed even by high-flux membrane dialyzers, is a strong inhibitor of mitochondrial respiration, and novel purification methods to remove CMPF from the blood of uremic patients should be developed. PMID- 8448925 TI - Effects of erythropoietin on strength and functional status of patients on hemodialysis. AB - The strength, endurance, and functional status of 15 anemic (HCT 21.2 +/- 4.6) hemodialysis patients was quantified prior to the administration of erythropoietin (epoetin) and after the anemia was partially corrected (HCT 35.4 +/- 2.3). Subjects showed significant increases in strength, measured isometrically (p < .01) and isokinetically (p < .01 at four of five speeds). They also demonstrated improved endurance and rated their functional ability higher. Anemia contributes to significant debilitation in hemodialysis patients and, when reversed with epoetin therapy, results in significantly improved muscle function and endurance. PMID- 8448926 TI - Intertransverse process lumbar arthrodesis with allogeneic fresh-frozen bone graft. AB - Nine patients were treated with ten intertransverse process lumbar spine anthrodeses using fresh-frozen crushed corticocancellous allogeneic bone as graft material. No instrumentation was used. The clinical and roentgenographic follow up period ranged from one to three years. Seven procedures showed successful arthrodesis and three demonstrated pseudarthroses. Increased age and systemic disease were associated with an increased risk of pseudarthrosis. Persistent back pain was associated with pseudarthrosis. Compared with 58 patients treated with intertransverse process lumbar fusion with autogeneic iliac bone as graft material, the overall fusion rate is inferior: 70% versus 92%, respectively. PMID- 8448928 TI - Chemonucleolysis. Personal history, trials, and tribulations. AB - This article is a review of the controversial history of chemonucleolysis. The review begins in 1963 and concludes with recent findings that demonstrated that in properly selected patients, chemonucleolysis can be as effective and safe as laminectomy. PMID- 8448927 TI - Methylmethacrylate plasma levels during total hip arthroplasty. AB - Methylmethacrylate (MMA) plasma concentrations were measured in 11 patients scheduled for total hip arthroplasty. After acetabular and after femoral cement implantation, sequential blood samples were withdrawn from pulmonary and radial artery catheters. The peak concentration of MMA (mean +/- standard error of the mean) in pulmonary artery blood occurred two minutes after cement implantation and was significantly higher after acetabulum (5.0 +/- 1.3 micrograms/ml) than after femoral cement insertion (1.9 +/- 0.6 micrograms/ml). The MMA peak in plasma was above 1 micrograms/ml in 13 cases, and the decrease fit a biexponential decay (r = 0.91). The initial half-life was 0.3 +/- 0.1 minutes, and the terminal half-life was 3 +/- 0.7 minutes. The areas under the curve (AUC) were determined for pulmonary (AUCpa) and radial (AUCra) plasma samples, and the ratio (AUCpa - AUCra)/AUCpa was computed: 55.1 +/- 7.8% of MMA was cleared during the transpulmonary passage. These results demonstrate that: (1) MMA could be determined after each cement implantation, (2) MMA plasma concentrations were higher after acetabulum than after femoral cement implantation, and (3) the half life is short and the total pulmonary clearance is high. PMID- 8448929 TI - Complications and results of scapho-trapezio-trapezoid arthrodesis. AB - Forty cases of scapho-trapezio-trapezoid (STT) arthrodesis were reviewed. Indications for the procedure included rotatory subluxation of the scaphoid (30 patients) and STT arthrosis (ten patients). Follow-up time averaged 41 months. Ten patients (25%) required 13 additional procedures: operations for nonunion or a fracture of the distal radius after bone harvesting, partial radial styloidectomy, first carpometacarpal joint arthroplasty, and wrist arthrodesis. Complications without surgeries were seen in several cases: pin-tract infection, sympathetic dystrophy, delayed union treated with brace, and radial nerve irritation. Overall, complications were observed in 21 patients (53%), some having more than one complication. Degenerative arthritis at joints surrounding the STT mass was suspected based on roentgenograms in five cases. Twenty-three patients (58%) became pain free or had minimal pain with a limited arc of motion. Twenty of 34 patients (59%) returned to their regular work or the same job, and 27 (68%) reported good to excellent results. Although STT arthrodesis can provide a painless wrist with a limited arc of motion in most patients, complications are frequent. PMID- 8448930 TI - Incidence and prognosis of coxarthrosis. 1964. AB - To define radiographic criteria, the radiographs of all patients diagnosed with coxarthrosis during the year 1951 were reviewed. Structural or joint space changes, evident radiographically in one of every seven cases in 1951, persisted at the time of the review in 1962. In the remaining cases, the diagnosis had been based upon the presence of osteophytic changes alone. Only one of 86 such cases reviewed in 1962 had structural or joint space changes. Osteophytes had no clinical significance and did not progress to coxarthrosis. Osteophytes appear to be a part of normal age changes. The radiographic diagnosis of coxarthrosis must be based on the demonstration of structural or joint changes. The natural history of coxarthrosis was studied by observing the course of the disease over a ten year period in all patients (168) with primary and secondary disease diagnosed during the five-year period, 1950-1954. About one in nine cases in this series was classified as secondary, and the sexes were equally well represented. The occurrence of bilateral disease in one third of the patients strongly suggested that primary coxarthrosis is a disease sui generis. Four out of ten patients died within ten years of diagnosis of the disease. PMID- 8448931 TI - Early migration of acetabular components revised with cement. A roentgen stereophotogrammetric study. AB - Roentgen stereophotogrammetric analysis (RSA) was used to evaluate the migration in 17 cemented acetabular components after revision operations for mechanical loosening. All of the hips were examined four months and one year after surgery; ten of the hips were also examined after two years. In 15 of the 17 components, definite migration (0.5-2.7 mm) was identified, whereas two acetabular components showed no significant migration (< 0.25 mm). In 13 hips, the migration was seen within four months after surgery. There was a tendency for larger migration in revisions for severe bone destruction. These findings indicate that prosthetic fixation in revision operations is relatively poor. In cases with severe bone loss, cement fixations is extremely poor. PMID- 8448932 TI - Torsional fixation of a modular femoral hip component. AB - Standard range of motion (S-ROM) modular total hip femoral stem has been designed to achieve precise fit in the diaphysis and metaphysis. This study compares torsional fixation of the S-ROM stem implanted with tight fixation of both the metaphyseal and diaphyseal components, tight metaphyseal and loose diaphyseal fixation. The mean load to failure was significantly greater in those implanted with tight fixation proximally and distally. Rotational micromotion was significantly decreased by fixation proximally, but permanent rotational displacement was improved primarily by distal fixation. Tight proximal and distal fixation were necessary to control both micromotion and permanent rotational displacement caused by torsional loading. Clinical success of this implant will depend on achieving tight proximal and distal fixation. PMID- 8448933 TI - A histologic and biochemical comparison of the interface tissues in cementless and cemented hip prostheses. AB - Thirty-four membranes from 20 cementless and 14 cemented prostheses from 33 patients excised during revision arthroplasty were analyzed for foreign-body reactive processes. As a control, identical analyses were performed using adjacent pseudocapsular tissue taken from 12 patients during revision arthroplasty. Histologically, cementless membranes tended to contain more metal debris, and cemented membranes contained more foreign-body giant cells. Collagenase, gelatinase, prostaglandin E2, and interleukin-1 were measured in conditioned media taken from organ cultures of each interface membrane. Both cementless and cemented membranes released significant levels of gelatinase and collagenase, prostaglandin E2, and interleukin-1 into the conditioned media when compared with control tissues. However, the tissue concentrations were not significantly different between cementless and cemented membranes. Although histologic differences between cementless and cemented interface membranes exist, both share a similar capacity to release bioactive products that can induce bone resorption and cause aseptic loosening of the hip prostheses. PMID- 8448934 TI - Cemented total hip arthroplasty in patients younger than 50 years of age. Ten- to 18-year results. AB - In ten- to 18-year clinical and roentgenographic results of 46 cemented total hip arthroplasties (THAs) in 34 patients younger than 50 years of age, surviving primary implants achieved a mean Harris hip score of 93 points. Survivorship analysis revealed failure rates of 2% at seven years, 10% at ten years, and 12.7% at 12 years. Roentgenographic analysis demonstrated either no signs of failure or benign mechanical failure modes in 73% of cases. No correlation was found between the Charnley category or the diagnosis and the clinical or the roentgenographic assessments. Cemented THA in the young would appear to provide durable restoration of hip function, with a revision rate similar to that reported in the elderly. For reliable early detection of progressive mechanical failure before loss of bone stock occurs, annual roentgenographic examinations are advisable. PMID- 8448935 TI - Congenital longitudinal deficiency of the fibula (fibular hemimelia). Parental refusal of amputation. AB - Fibular hemimelia with significant limb-length inequality is usually best treated with foot ablation and prosthetic fitting. Parents tend to be reluctant to agree to allow their child's foot to be amputated at an early age, especially when the foot is near normal and the limb length is not grossly abnormal. Experience with some families of children with fibular hemimelia who initially refused amputation of the affected limb prompted a retrospective review of the treatment experience with these children. Twenty-four children with 36 affected limbs were treated during the last three decades. Amputation of the foot was performed for 16 limbs in 12 of the 24 patients. The 12 patients whose limbs were not amputated were reviewed in detail. Six of these children were advised to have an amputation, but their families refused to consent. These children were managed by specially designed prostheses to incorporate their foot deformity and limb-length inequality. Four patients required subsequent corrective surgical procedures in an attempt to stabilize the feet or lengthen the limb. To facilitate treatment decisions for both the clinic team as well as the involved families, the authors propose a more practical classification of fibular hemimelia. PMID- 8448936 TI - Repair of nonunion of tibial osteotomy. AB - Nonunion after high tibial osteotomy is an uncommon complication. Ten cases have been treated with a single plate; failure occurred twice in five. Double plates, bolted together, healed in all five attempts. Although the healed osteotomies had only "fair" functional results, none have as yet required total knee arthroplasty (TKA). PMID- 8448937 TI - The effects of axial rotational alignment of the femoral component on knee stability and patellar tracking in total knee arthroplasty demonstrated on autopsy specimens. AB - Four fresh-frozen anatomic knee specimens were tested for knee stability, patellar tracking, and patellofemoral contact points with the femoral component positioned in 5 degrees internal, 5 degrees external, or neutral axial rotational alignment of the femoral component referenced on the posterior femoral condyles. The externally rotated specimens had varus-valgus stability of the knee that was closest to the normal control. The internally rotated specimens shifted into valgus alignment with flexion. Patellar tracking also was closest to normal in the externally rotated specimens. Patellofemoral contact was more evenly distributed between the medial and lateral contact areas in the externally rotated specimens than in the internally rotated or in the neutral specimens. Internal rotation of the femoral component in the knee with perpendicular resection of the tibia causes undesirable changes in knee stability, patellar tracking, and patellofemoral contact points. Neutral positioning produces similar but less negative effects on knee stability and patellar kinematics. External rotation improves both patellar tracking and knee stability characteristics. PMID- 8448938 TI - Evaluation of the effect of the femoral articular surface material on the wear of a metal-backed patellar component. AB - Wear characteristics of metal-backed, polyethylene patellar components were tested using cobalt-chromium, titanium alloy (Ti), and ion-implanted titanium alloy (IITi) articular surfaces. Patellar components were cycled in a bovine serum bath at 3 Hz for 1 million cycles, under a compressive load that varied from 343 N at 0 degree flexion to 2255 N at 120 degrees flexion. After testing, the polyethylene articular surfaces of the patellar components were evaluated for wear and graded using a subjective numbering system. Overall wear damage to the polyethylene surface was much worse with both Ti and IITi than with cobalt chromium. Differences in mean wear scores were statistically significant when cobalt-chromium was compared with either Ti or IITi, but there were no statistically significant differences between Ti and IITi. Polyethylene surfaces that articulated against Ti femoral surfaces had more severe scratching. The IITi test group had areas of delamination not observed in the other test groups. Subjective evaluation of the metal surfaces showed evidence of wear damage as well. The metal articular surface of IITi resisted scratching as long as the treated surface was intact. In the high-stress areas, however, such as the edges of the intercondylar notch, the ion-implanted surface quickly wore away, exposing the untreated titanium alloy. The cobalt-chromium femoral articular surface had the least amount of scratching and no evidence of loss of metal. PMID- 8448939 TI - Congenital dislocation of the knee. Its pathologic features and treatment. AB - Arthrograms and operative findings of 19 patients with 26 congenital dislocations of the knee (CDK) were reviewed to clarify the pathologic features, methods of treatment, and the optimum treatment for the patient with multiple joint deformities. The fundamental pathologic features in CDK involved a shortening of the quadriceps femoris tendon, a tight anterior articular capsule, and hypoplasia of the suprapatellar bursa. Valgus deformity of the knee, which was observed in half of the patients, was caused by the fragility of the medial components of the knee. This fragility was attributable to the forward displacement of the tibial insertion of the medial components. Arthrograms served as effective indicators when evaluating the pathologic features and determining the applicability of surgical therapy. There were limits to conservative therapy that were dependent on the extent of the pathologic changes. In extremely refractory patients with arthrogryposis multiplex congenita (AMC), an elimination of genu recurvatum and an improved range of movement could be obtained by the use of surgery. The valgus deformity was significantly reduced by invasive treatment that reinforced the fragile inner components. Experience with nine patients with multiple lower-limb joint deformities indicates that the knee dislocation should be treated before any of the other deformities. PMID- 8448940 TI - Does osteoarthrosis depend on growth of the mineralized layer of cartilage? AB - Osteoarthrosis (OA) cannot be adequately studied in exclusively biologic biochemical terms or exclusively mechanical terms. A common but unproven theory states that OA is primarily a degenerative disease of the cartilage with secondary bone changes. However, there are reasons to believe that primary OA is actually a disorder of the entire joint end, consisting of a reactivation of growth factors in the mineralized part of the joint cartilage (remnants of the growth cartilage of the joint head in childhood). Some growth occurs normally in loaded joints in elderly people. When the joint head expands, the cartilage is mechanically injured by stiffness gradients or impaired nutrition. Attempts to heal the wounds and phagocytosis of detritus release cytokines, enzymes, and additional growth factors within the joint cavity. The released factors in the joint, together with the continuous loading, produce all the typical osteoarthritic changes in cartilage, subchondral bone, and the joint capsule, with stasis and increased bone marrow pressure. PMID- 8448941 TI - Revision of failed unicompartmental total knee arthroplasty. AB - Forty-eight revision total knee arthroplasties (TKAs) for failed unicompartmental total knee prostheses were evaluated at 5.4 +/- 2.5 years after revision. The most frequent mode of failure of the original arthroplasty was loosening. All revisions used a condylar-type prosthesis. Fifty percent of the knees had bone defects that were filled with cement. Good or excellent results were achieved in 81% of the knees. One knee had a complete radiolucent line adjacent to the tibia at last evaluation. The surgical complication rate was 13%. Predictable salvage of the failed unicompartmental TKA can be achieved by revision arthroplasty. PMID- 8448942 TI - Advances in Sweden. A tribute to Goran Bauer. PMID- 8448943 TI - Lateral presentation of a Baker's cyst. AB - Lateral presentation of a Baker's cyst occurred in a 27-year-old woman. The popliteal origin of the cyst was diagnosed by computed tomography and confirmed by surgery and histologic examination. Lateral presentation of a Baker's cyst is rare. PMID- 8448944 TI - Simple bone cyst. Treatment by trepanation and studies on bone resorptive factors in cyst fluid with a theory of its pathogenesis. AB - Simple bone cysts were treated by trepanation. The technique consists of drainage of cyst fluid, lavage of the cystic cavity with saline, and the making of multiple drilling holes through the cortical and the medullary bone of the cyst wall. Injection of corticosteroid was omitted. In 11 cases treated by this method, the clinical outcome was good. Biochemical analyses of the cyst fluid showed bone-resorptive factors, i.e., prostaglandins, interleukin 1, proteolytic enzymes. Electrophoretic analysis of proteolytic enzymes in polyacrylamide gel containing sodium dodecyl sulfate and polymerized gelatin showed proteins with molecular weights of about 130,000, 92,000, 72,000, and lower than 50,000. Increase in such bone-resorbing activities seems to be one of the causative factors in simple bone cysts. The technique was effective in decompressing the internal pressure of the cysts, improving the blood flow through the medullary bone of the cyst wall, stimulating the periosteum to induce bone formation, and eliminating bone destruction. PMID- 8448945 TI - Multiple hereditary exostoses. An epidemiologic study of an isolated community in Manitoba. AB - From 1986 through 1988, 266 persons (149 adults and 117 children) were screened for multiple hereditary exostosis (MHE) in an isolated northern Ojibway community. Physical examination and confirmation by roentgenogram skeletal survey disclosed 21 children (19.4%) and 14 adults (9.5%) affected with MHE. Forty-one percent of children had lesions detectable before ten years of age, some as early as two years of age. Seventy-four percent of the lesions were characteristically sessile. Although lesions about the knee were most common, sites previously thought to be uncommon such as the metatarsals, hand, and spine were involved in 40% of the children. No cases of malignant degeneration have occurred in the adult population. Severity and multiplicity of lesions in successive generations point to an oncogenic gene origin. This study shows striking variance from current literature and provides a unique and valuable baseline assessment of research on the cause and natural history of MHE. PMID- 8448946 TI - The Maisonneuve fracture of the fibula. AB - Nine patients sustained a Maisonneuve fracture of the fibula (MFF), which is a proximal fibula fracture associated with an ankle fracture or deltoid ligament tear. Eight were treated with closed reduction and plaster casts. One was treated by open reduction and internal fixation. Reexamination was performed at an average of 25.7 months. This included subjective, objective, and functional evaluations, along with stress roentgenograms. Six patients had an excellent result, two a good result, and one a fair result. The MFF is often more stable than generally assumed. For injuries with only a partial syndesmotic disruption, nonoperative treatment is recommended. PMID- 8448947 TI - Treatment of segmental femoral shaft fractures. AB - In a prospective study, 35 segmental femoral shaft fractures were treated either with closed intramedullary nails (most were Grosse-Kempf interlocking nails) or an open method technique (most were open Kuntscher nails with supplementary wires). The follow-up period was at least one year. There was an 82.9% (29/35) union rate and a union period of 6.1 +/- 1.9 months. Knee range of motion was on average 125 degrees. Although there was no statistical difference, the closed intramedullary nailing group showed superiority to the open method group. Complications were not particularly different from those in other type fractures, but could be managed better. Closed nailing technique can be improved with training and experience. Whenever possible, with adequate indications, closed intramedullary nailing is better than open treatment for segmental femoral shaft fractures. PMID- 8448948 TI - Fibular nonunion after fixation of the tibia in lower leg fractures. AB - In 335 extraarticular tibial-fibular fractures treated by open reduction of the tibia, nonunion of the fibula was noted in 15 cases (4.5%). Four of these cases were symptomatic, but resection of the hypertrophic nonunion provided relief of pain. Fixation of the fibula is not necessary in primary treatment of extraarticular lower leg fractures. PMID- 8448949 TI - Thorn synovitis of the knee joint with Nocardia pyarthrosis. AB - Pyarthrosis of the knee with Nocardia asteroides occurred concomitantly with thorn synovitis in an 11-year-old boy who was otherwise healthy. A review of the orthopedic and infectious disease literatures did not disclose a similar report. Contrary to common teaching, effusions from joints violated by thorns should not be presumed sterile. Culture for bacterial and fungal infections is recommended when treating cases of thorn synovitis. PMID- 8448950 TI - The use of lower tourniquet inflation pressures in extremity surgery facilitated by curved and wide tourniquets and an integrated cuff inflation system. AB - Use of the lowest possible cuff inflation pressure should minimize the pathogenic effects of compression beneath the pneumatic tourniquet. Curved tourniquets (designed to fit conically shaped limbs) and wider tourniquets were associated with significantly lower arterial occlusion pressure (AOP) than standard, straight tourniquets on the arms and legs of 26 normal volunteers. These tourniquets were used with an integrated tourniquet inflation system in 29 upper extremity and 31 lower-extremity surgeries. Mean tourniquet inflation pressures of 183.7 mm Hg and 208 mm Hg were used during various surgical procedures of the arm and leg, respectively. Incomplete hemostasis was associated with elevated systolic blood pressure in several cases, but acceptable surgical hemostasis was achieved by incremental increase of the cuff inflation pressure. Curved cuffs, wide cuffs, and an integrated cuff inflation system should facilitate the use of lower tourniquet inflation pressures in extremity surgery. PMID- 8448951 TI - Closed intramedullary femoral osteotomy. Shortening and derotation procedures. AB - Closed osteotomy and nailing were performed on 37 patients for leg-length inequality or rotational deformities. Shortening operations were performed in 31 patients, derotation in six. Preoperatively, the leg-length discrepancy ranged from 2 to 6.6 cm. All femoral shortenings resulted in correction to less than 1 cm. Preoperatively, rotational deformities averaged 58 degrees; all were corrected to within 5 degrees of normal. Follow-up observation averaged 3.3 years. There were no nonunions or infections. All patients regained preoperative joint range of motion (ROM). Thirteen patients were Cybex tested one year or more postoperatively; all had quadriceps and hamstring strength equal to or greater than the contralateral leg, except for two patients who had suffered additional trauma to the shortened femur. Closed femoral osteotomy is an effective, safe, and reproducible means to obtain lower limb length correction in patients with leg-length inequality or rotational abnormality. PMID- 8448952 TI - Radiocolloid uptake in spontaneous osteonecrosis of the knee. A case report. AB - Bone marrow scintigraphy, including radionuclide angiography in a 66-year-old woman with spontaneous osteonecrosis of the medial femoral condyle, showed a marked increase in radiocolloid uptake in the affected condyle. Radiocolloid uptake (reflecting phagocytic activity at the osteonecrotic lesion) was correlated with findings on roentgenography, three-phase bone scintigraphy, and magnetic resonance imaging. PMID- 8448953 TI - Would revision arthroplasty be facilitated by extracorporeal shock wave lithotripsy? An evaluation including whole bone strength in dogs. AB - Extracorporeal shock-wave lithotripsy has been proposed as a modality to facilitate the removal of bone cement during revision arthroplasty; however, concomitant cortical microfractures have been reported. The current study examines the effect on whole bone strength of extracorporeal shock-wave lithotripsy directed at the cement-bone complex. Canine femora were subjected to manual cement extraction or lithotripsy followed by manual cement extraction. Contralateral femora served as controls. Torsional fractures were created, and maximum torque, maximum angular displacement, and energy capacity to failure were determined. Although cement extraction alone reduced mean torque by 6.6% and failed to reduce mean torque angle or mean energy capacity, the combination of lithotripsy and cement extraction reduced mean torque by 7.3%, mean torque angle by 14.3%, and mean energy capacity by 18.3%. No statistical significance was demonstrated between the two groups in torque, angle, or energy capacity. At magnitudes and numbers of shock waves previously shown to significantly reduce cement-bone interface mechanical strength, lithotripsy exposure had a minimal and insignificant effect on whole bone strength. PMID- 8448954 TI - Histochemical and immunohistochemical characterization of cells constituting the giant cell tumor of bone. AB - Enzymatic activity and cell membrane proteins were characterized in cells from five giant cell tumors of bone (GCTs). Naphthyl alpha esterase (NAE) and acid phosphatase (AP) activity was noted within both the mononuclear and multinucleated cells of each tumor. In each tumor, all mononucleated cell populations displayed tartrate-sensitive AP activity, whereas the multinucleated cell populations demonstrated variable expression of tartrate-sensitive and tartrate-resistant AP activity. Analysis of cell membrane proteins included attempts at immunodetection of mannose receptor, OKM-1 antigen (OKM-1a), colony stimulating factor-1 receptor (CSF-1r), and platelet-derived growth factor receptor (PDGFr). None of these membrane antigens were elicited on multinucleated cells. In contrast, the mannose receptor, OKM-1a, and PDGFr all were detected on the mononucleated cells within each tumor. These data demonstrate that a population of mononucleated, not multinucleated cells, expresses features unique to mature mononuclear phagocytes and establishes the presence of a membrane receptor, PDGFr, associated with mitogenesis of mesenchymal cells. PMID- 8448955 TI - Osteogenesis in sintered bone combined with bovine bone morphogenetic protein. AB - Bone morphogenetic protein (BMP) was combined with true bone ceramic (TBC) in an attempt to produce a bone grafting material possessing the cancellous structure, osteoconductivity, and osteoinductivity of biologic bone. To determine the osteogenetic ability of this material (BMP-TBC) within bone marrow, BMP-TBC and TBC alone were implanted in the femoral condyles of Japanese White rabbits, and histographs of these implants, taken serially, were compared. Woven bone formation was observed both at the periphery and within surface pores of the BMP TBC implants one week after implantation; these implants thus became secured to the host bone bed at an earlier stage than did TBC alone. The amount of new bone formation increased at a significantly higher rate with BMP-TBC than with TBC alone during the first four weeks. Therefore the BMP in BMP-TBC implants acts at an early stage on BMP-responding cells entering the pores of the TBC. These data also suggest that TBC, as a carrier for BMP, provides a favorable environment for the promotion of new bone formation. PMID- 8448956 TI - Posttraumatic limb swelling and joint stiffness are not causally related experimental observations in rabbits. AB - Periarticular and intraarticular fractures frequently cause limb swelling and joint stiffness. The two effects are widely assumed to be related--an assumption long held but never tested. Over a ten-year period, a rabbit hind limb model was developed and tested to ascertain methods of preventing or reducing limb swelling and joint stiffness after a local skeletal injury. Limb swelling was monitored for the three- to four-week duration of the studies by volume displacement, and joint stiffness was determined arthrographically. Mechanical treatment modalities tested included limb pressurization, passive motion of varying duration (from four to 24 hours daily), creation of an intraarticular hematoma, and creation of dependent edema. Chemical modalities tested included systemic and intraarticular steroids, intramuscular and oral nonsteroidal antiinflammatory drugs, topical dimethyl sulfoxide, two antihistamine drugs, and two diuretics. At statistically significant levels, all of the modalities tested affected swelling or stiffness, but only terfenadine, an antihistamine, affected both. Treatment with terfenadine resulted in decreased stiffness but increased swelling. When reviewing the results of all of the treatment modalities in concert, it is apparent that, in this model, limb swelling and joint stiffness after injury are not causally related. The significance of this work in forthcoming clinical trials for treatment of posttraumatic joint stiffness are noteworthy. PMID- 8448957 TI - The use of radionuclides in orthopaedics. Radionuclide scintimetry of the skeleton. 1968. PMID- 8448958 TI - Instability and femoral head vitality in fractures of the femoral neck. AB - Sixteen patients with femoral neck fractures were studied with roentgen stereophotogrammetric analysis (RSA) and low-field magnetic resonance (MR) imaging in addition to plain roentgenography. In six patients, these results were compared with the results of histopathologic analyses. All fractures were stabilized with two cannulated titanium screws. Evaluation of fracture movement before weight bearing (nine fractures) revealed no or only slight movement (less than 3.4 mm or 4.7 degrees). During weight bearing, two undisplaced fractures were compressed about 5 mm and one 20.3 mm, because of delayed union, which was verified by repeated RSA measurements and MR imaging. The average compression in nine displaced fractures that subsequently healed was 13.3 mm. MR imaging revealed signs of femoral head necrosis in three healed and two unhealed fractures. Segmental or total femoral head necrosis was histologically confirmed in all removed femoral heads, and the fracture areas were shown to be bridged by bone trabeculae to a varying degree. Absence of micromovement six months after fracture implied uncomplicated healing. Fracture stabilization at nine to 12 months postfracture was associated with femoral head necrosis or delayed union in four of six cases. Micromotion after more than one year indicated femoral head necrosis or pseudarthrosis. PMID- 8448959 TI - Background factors to hip fractures. AB - A questionnaire was distributed to 159 patients with cervical or trochanteric hip fractures about the cause of their accident, their health status, and various social factors. The purpose was to compare background factors in hip fracture patients with factors in subjects without hip fracture. The responses from 102 patients were compared with 102 age- and gender-matched controls. Most patients had fallen during walking or rising, and they often fell sideways. Patients had had more symptoms of diseases, were more often afraid of falling, and were less active than control subjects. Hip fracture patients, even prior to fracture, were more frail and sedentary than average. Fracture prevention training is an important consideration in elderly patients. PMID- 8448960 TI - Subsidence, tip, and hump micromovements of noncoated ribbed femoral prostheses. AB - The micromovements of 18 ribbed femoral prostheses were measured for two years postoperatively. Repeated roentgen stereophotogrammetric examinations (RSA) were used to measure distal migration of the center of the prostheses and movements of the prosthetic hump and tip. During the first six postoperative months, an increasing number of prostheses migrated significantly. Migration was first observed at the tip. Two years after the operation, one prosthesis had been revised because of pain. Thirteen of 17 remaining prostheses had subsided, 12 displayed hump and 16 tip migration, and eight had rotated about the longitudinal axis of the femur. In these hips, the instant center of rotation ran obliquely through the greater trochanter or the isthmus of the femur. Clinical follow-up examination and measurements on conventional roentgenograms disclosed a correlation between pain, the extent of sclerosis surrounding the prostheses, and the distal migration according to RSA measurements. PMID- 8448961 TI - 99mTc-diphosphonate scintigraphy in successful knee arthroplasty and its relation to micromotion. AB - Nineteen tibial components after successful knee arthroplasty were studied with technetium 99m scintigraphy. All cases were also followed from the operation with roentgen stereophotogrammetric analysis (RSA). All but three cases became stable after an initial period of migration. Scintigraphic uptake was found in all cases, with a ratio as high as seven in the medial compartment and three in the lateral compartment. A group of cases with proven mechanical loosening showed an uptake ratio as high as 6.9 in the medial compartment and 5.5 in the lateral compartment. No correlation was found between scintigraphic uptake and alignment, whether cement was used, or the presence/absence of migration. Technetium 99m scintigraphy is not a useful method for assessing loosening in individual symptomatic cases of knee arthroplasty. PMID- 8448962 TI - Size of osteonecrosis of the knee. AB - In the Swedish Multicenter Study of Knee Arthroplasty, 115 knees in 110 patients with knee osteonecrosis represented all reported cases treated with knee arthroplasty in the period from 1975 to 1986. Primary medial femoral condyle osteonecrosis was the most common osteonecrosis reported (89%). Preoperative roentgenograms were staged according to the type of osteonecrosis and classified according to the grade of arthrosis. Detailed measurements of the size of the lesion were also performed. For primary medial femoral osteonecrosis, the width of the lesion averaged 45% of the condyle. The mean width of the lesion (anteroposterior size) was 21 mm and the mean length (lateral size) was 34 mm. The mean depth on lateral roentgenograms was 6 mm. There was a high correlation of results among the various methods of measurement. Using regression analysis, it was possible to approximate the volume of the lesion even from a single measurement of the width on anteroposterior view. The size of osteonecrosis of the knee can be used to plan resection and select the implant design. PMID- 8448963 TI - Predicting results of rehabilitation after hip fracture. A ten-year follow-up study. AB - Data influencing the outcome of rehabilitation after hip fracture were obtained from 103 consecutive patients. All were admitted from their own homes and were observed at the time of discharge from the hospital and at three weeks, four months, one year, five years, and ten years postfracture. Background and functional variables were recorded and analyzed by means of multivariate discriminant statistical techniques. The three most important variables for discharge to home were (1) the ability to walk two weeks after surgery, (2) living with someone, and (3) good general health. From four months until ten years postfracture, the most persistent positive variable for returning to and living at home was an active prefracture lifestyle. The most persistent negative variable was old age. By means of prognostic schemes, it is possible, as early as the time of fracture or a few days after surgery, to make a reliable prediction as to whether the patient will return home. Both the patient and society benefit from early rehabilitation at home in cooperation with primary care personnel and social workers, as it reduces the cost of the injury by avoiding a lengthy hospital stay and unnecessary institutional aftercare. PMID- 8448964 TI - Coxarthrosis in farmers. AB - Recent studies have suggested an excess of coxarthrosis (osteoarthrosis of the hip joint) among Swedish farmers. The prevalence of coxarthrosis in the city of Malmo has previously been studied by coincidental examination of the hip joints on colon roentgenograms. The present study estimates the prevalence of coxarthrosis in farmers by examining the hip joint on roentgenograms of the colon and urinary tract. Fifteen-thousand farmers and farm workers affiliated with the Swedish Farmers' Safety and Preventive Health Association and all farmers aged 40 years or older in the Swedish country of Ostergotland were questioned about previous roentgenographic examinations. Four hundred thirty-five colon examinations and 465 urograms were available and scrutinized by the same physician. Forty-five of 565 male farmers and farm workers, aged 40-64 years, were found to have roentgenographic signs of primary coxarthrosis, compared with ten of 1250 men in the corresponding age group in the urban population of Malmo. The difference represents a rate ratio of 12 with a 95% confidence interval of 6.7 to 21.4. There was no difference in the prevalence of coxarthrosis among the female farmers and women in the urban population. The result suggests a relationship between coxarthrosis and farm work in men. PMID- 8448965 TI - Fracture incidence after tibial shaft fractures. A 30-year follow-up study. AB - Based on all patients with tibial shaft fracture (n = 767) treated in the department of orthopedics in Malmo from 1955 to 1963, a retrospective cohort study was performed in 1990. Two hundred sixty-nine of the patients were still living in Malmo or had died in the city. Since all roentgenograms were available, all other fractures that this group of patients had sustained up to 1990 were included. Data were compared with an age- and gender-matched control group with respect to location and types of fractures. The group with previous tibial shaft fractures had an increased incidence of all sorts of fractures. When comparing the risk of sustaining new fractures in the previously fractured limb with the uninjured side, only a statistically insignificant tendency toward more fractures was found. A similar tendency was observed in fractures of the upper limb. Therefore, remaining osteopenia in the injured limb after tibial shaft fracture is not associated with further fractures; rather, this group of patients were more fracture prone in general. PMID- 8448966 TI - Bone mass--a marker of biologic age? AB - One thousand one hundred ninety-two subjects who had the bone mineral content (BMC) of their forearm measured during the period spanning 1970-1976 were followed to 1985. At that time, 489 had died. Those who died had a lower BMC of the forearm at the time of the measurement than did the survivors. However, the difference was significant only in men aged 50-69 years. In men, deviation below normal BMC was an indicator of a shorter than average life expectancy, whereas above average values were not important in this respect. PMID- 8448967 TI - Reduced failure rate in knee prosthetic surgery with improved implantation technique. AB - From the Swedish Knee Arthroplasty project, started in 1975, types of relatively unmodified knee prostheses were chosen for analysis of time-dependent changes in the failure rate. One thousand nine hundred sixty-nine Marmor unicompartmental and 376 Total Condylar arthroplasties, all cemented, were followed until the end of 1989. The cumulative revision rates calculated with survival statistics showed a continuous improvement with time. The five-year revision rate was reduced from 11% to 5% for the Marmor prosthesis and from 10% to 2% for the Total Condylar prosthesis. This indicates that factors other than improved design are important. Such factors could include improved guide instruments, better surgical and cementing technique, influence of a learning curve, and patient selection. PMID- 8448968 TI - Pyogenic sacroiliitis in children. AB - Clinical findings, roentgenograms, computed axial tomography (CT scan), radionuclide studies, and management are reviewed in seven children with pyogenic sacroiliitis (PS). High suspicion and complete examination of the pelvis and sacroiliac (SI) joint, including flexion, abduction, external rotation, and extension (FABERE) test, are essential for diagnosis. Although initial roentgenograms may be negative, CT scan will show changes indicating involvement of the SI joint. Sequential technetium and gallium scans are valuable in localizing PS. Blood cultures and direct aspiration of the SI joint will identify the infecting organism. Patients are initially treated with intravenous antibiotics. Surgical treatment is reserved for patients with advanced stage of PS. PMID- 8448969 TI - Trends in clinical pharmacokinetics. PMID- 8448970 TI - Clinical pharmacokinetics of fluconazole. AB - Fluconazole was recently developed for the treatment of superficial and systemic fungal infections. Triazole groups and insertion of 2 fluoride atoms increase the polarity and hydrosolubility of the drug, allowing it to be used in a parenteral form. Bioassay methods using Candida pseudotropicalis as a test organism were the first techniques used for the determination of fluconazole in body fluids. Gas chromatographic and high performance liquid chromatographic methods were later developed with better accuracy and sensitivity. Prediction of efficacious concentrations in patients from the minimum inhibitory concentrations in vitro seems to be uncertain because of low efficacy of the drug on some yeasts in vitro compared with efficacy in vivo in animal models. Oral forms (capsule and solution) are quickly absorbed and bioavailability is nearly complete (about 90%). Plasma protein binding is low (11 to 12%) and fluconazole circulates as active drug. Distribution is extensive throughout the tissues and allows the treatment of a variety of systemic fungal infections. The average elimination half-life (t1/2) of 31.6 +/- 4.9h is long, with a minimum of 6 days needed to reach steady-state; thus, a loading dose (equal to double the maintenance dose) is recommended. The metabolism of fluconazole is not qualitatively or quantitatively significant. The main route of elimination is renal. The mean +/- SD (calculated from published data) total and renal clearance values are 19.5 +/- 4.7 and 14.7 +/- 3.7 ml/min (1.17 +/- 0.28 and 0.88 +/- 0.22 L/h), respectively. Concentrations of fluconazole in blood after administration of single doses correlated well with the administered dose. There was very little interassay variation between the data reported in literature. Concentrations in blood after multiple doses also exhibit little variation and the accumulation factor was between 2.1 and 2.8. Fluconazole was found in many body fluids, especially in cerebrospinal fluid and dialysis fluid, allowing the treatment of systemic fungal infections such as coccidioidal meningitis and fungal peritonitis. Concentrations of 1 to 3 mg/L and 20 mg/L are the extreme values expected in clinical practice. In renal insufficiency the fluconazole t1/2 is longer, requiring dosage adjustment in relation to creatinine clearance. In continuous ambulatory peritoneal dialysis a 150mg dose in a 2L dialysis solution every 2 days has been proposed. In haemodialysis, a dose of 100 or 200mg should be given at the end of each dialysis session. Neither old age nor irradiation affect fluconazole pharmacokinetics, but the t1/2 was shorter in children.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8448972 TI - Clinical pharmacokinetics of newer antibacterial agents in liver disease. AB - Liver disease may produce significant, albeit highly variable, effects on the pharmacokinetic behaviour of antibiotics in serum. Drug disposition may be altered through several pathophysiological mechanisms including reduced hepatobiliary clearance, and modifications in the volume of distribution induced by albumin synthesis deficiency or portal hypertension-related ascites. Antibacterial agents are not affected by potential alteration in hepatic first pass effects. Only liver cirrhosis-induced effects on serum pharmacokinetics of antibiotics have been extensively studied, unlike those possibly produced by other forms of liver disease. In liver cirrhosis, pharmacokinetic alterations of nearly all beta-lactam or quinolone agents appear not to be marked enough to require dosage adjustment, provided that renal function stays normal. Adaptation in therapeutic schedule, however, is warranted for those drugs that are substantially cleared by the hepatobiliary system, namely mezlocillin, clindamycin, erythromycin, pefloxacin, enoxacin, antituberculous agents or nitroimidazole derivatives. Special caution should also be exercised when using aminoglycosides or vancomycin because of the wide interpatient variability of their pharmacokinetic disposition and their toxic potential. When renal function is impaired and there is an increased volume of distribution due to ascites, as frequently observed in severe liver insufficiency, the elimination half-life of most antibiotics is markedly prolonged, resulting in potential side effects due to drug accumulation. Accordingly, dosage adjustment applies to all drugs. In this regard, it should be remembered that delineating the dosage guidelines for a given antibiotic on the basis of reported pharmacokinetic parameters in patients with liver cirrhosis is awkward and probably of limited value. This pattern is ascribed to large interpatient variability in the active hepatic cell mass, the degree of portal hypertension and the alteration of serum binding capacity. Furthermore, there is no way of predicting accurately the extent of liver insufficiency in an individual patient. Dosage reduction is thus done empirically in most cases. Whenever possible, direct measurements of serum antibiotic concentrations should be the reasonable approach to manage antibiotic therapy in this kind of clinical condition. PMID- 8448973 TI - Optimising ACE inhibitor therapy of congestive heart failure. Insights from pharmacodynamic studies. AB - Pharmacokinetic studies are often used to provide additional information regarding the use of pharmacological agents for the treatment of cardiovascular disorders. Pharmacokinetic data are available for the major angiotensin converting enzyme (ACE) inhibitors. However, practical guidelines regarding dosage and dosage intervals are not feasible, and measurements of serum drug concentrations are generally not useful in practice. Such use is obscured by the nature of enzymatic inhibition, renin and angiotensin I accumulation, the complex interaction of several organ systems, the compromise of organ system function due to the heart failure process, the effect of ACE inhibitors on other vasoactive substances and the cellular actions of carboxypeptidase (the enzyme otherwise known as ACE). Pharmacodynamic data demonstrate 2 important factors that influence ACE inhibitor pharmacokinetics and serum concentrations: the aging process and abnormal renal function. As most patients with moderate to severe heart failure have reduced renal function, this has practical implications. Furthermore, heart failure is common in the elderly, and even within the population with heart failure, a superimposed further reduction in renal function can be identified in elderly patients with heart failure. Therefore, a more careful analysis of ACE inhibitor dosage must be made in the presence of decreased renal function and in the elderly patient with heart failure. PMID- 8448971 TI - Atrial natriuretic peptide. An overview of clinical pharmacology and pharmacokinetics. AB - The atrial natriuretic peptide (ANP) is part of a new family of cardiac hormones regulating water and salt homeostasis. Besides acting as a blood pressure lowering agent, it also exerts potent natriuretic and diuretic effects. ANP can be considered an endogenous antagonist of the reninangiotensin-aldosterone system and the antidiuretic hormone. One of the roles of ANP is to protect the body against fluid overload: it decreases intravascular fluid volume, which in turn diminishes cardiac secretion of ANP. The pharmacokinetic parameters of ANP reported in the literature vary widely. In general, ANP rapidly disappears from plasma with a high total body clearance. This is in agreement with the short lived effects of the hormone. The actions of ANP have led to efforts to use this peptide hormone in the treatment of various cardiovascular disorders such as hypertension and congestive heart failure. Intravenous ANP administration indeed resulted in beneficial effects in these disorders. However, the peptide nature of ANP and its rapid elimination from the circulation limit its suitability as a drug. More promising is the development of long-acting ANP analogues and inhibitors of ANP degradation. Proper understanding of ANP pharmacokinetics is essential for the clinical use of these pharmacological agents. PMID- 8448974 TI - Pharmacokinetics of [14C]omeprazole in patients with liver cirrhosis. AB - The pharmacokinetics of omeprazole and its metabolites following single doses were studied in 8 patients with liver cirrhosis. Each patient participated in 2 experiments in which [14C]omeprazole was administered either intravenously (20mg) or in an oral solution (40mg) in a randomised crossover design. Plasma concentrations of omeprazole and 2 of its identified metabolites, as well as total radioactivity were followed for 24h; urinary excretion was followed for 96h. The mean elimination half-life of omeprazole in the patients with cirrhosis was 2.8h and the mean total plasma clearance was 67 ml/min (4.02 L/h); corresponding values from separate studies in young healthy volunteers were 0.7h and 594 ml/min (35.64 L/h). The mean systemic availability was nearly 100% in the patients with cirrhosis whereas the previously reported value in young volunteers was only 56%. Almost 80% of a given dose was excreted as urinary metabolites in both patients and young volunteers. It is concluded that, as the hepatic clearance of omeprazole was substantially reduced in these patients, the dose of omeprazole needed for a certain degree of acid suppression is lower in patients with liver cirrhosis. PMID- 8448975 TI - Aminoglycoside forecasting in neutropenic patients with cancer. AB - To validate the population pharmacokinetic parameters of aminoglycoside disposition in patients with cancer, a retrospective evaluation of predictive performance of a Bayesian program was performed in 155 patients from 1986 to 1989 who received amikacin, gentamicin or tobramycin. Each patient received 1 of the 3 drugs and had initial drug concentration determination, with a second set of drug concentrations drawn < or = 14 days after the initial dose. Predictions of 64 amikacin, 144 gentamicin and 102 tobramycin concentrations were generated using 1 compartment model pharmacokinetic parameters, serum creatinine values, patients' dosage history and demographic data. The mean (+/- SD) observed (and predicted) serum concentrations for amikacin were 18.9 +/- 14.8 mg/L (17.2 +/- 14.1 mg/L); for gentamicin were 4.49 +/- 3.58 mg/L (4.26 +/- 3.33 mg/L) and for tobramycin were 4.52 +/- 3.70 mg/L (4.05 +/- 3.49 mg/L) [p > 0.05]. Results demonstrated minimal bias with a mean error in gentamicin concentrations of -0.236 (95% CI 0.533: 0.0613). Significant (p < 0.05) under prediction occurred in concentrations of tobramycin [-0.474 mg/L (95% CI -0.842: -0.0107)] and amikacin [-1.77 mg/L (95% CI -3.42: -0.114)]. Good precision is indicated by a mean squared error for gentamicin of 3.35 mg/L (95% CI 1.70: 4.99) and for tobramycin of 3.64 mg/L (95% CI 1.83: 5.44). Fair precision is demonstrated by amikacin [46.1 mg/L (95% CI 27.3: 65.0)]. Similar results were shown in a separate peak/trough analysis. These data indicate that aminoglycoside pharmacokinetics in patients with cancer can be predicted with minimal bias and good precision using a Bayesian forecasting program for gentamicin and tobramycin. PMID- 8448976 TI - Factors related to integrating persons with chronic mental illness into a peer social milieu. AB - Client characteristics and their perceptions of the milieu in a psychosocial rehabilitation program were used to predict the clients' level of involvement in the peer-based social network. 81 clients in a psychosocial rehabilitation program participated in the study. The results indicated that client perceptions of higher support and clarity in the staff-client milieu, and being female, were strongly related to higher peer social involvement. Milieu factors were generally more important than client characteristics in predicting client social functioning. The implications of these findings for psychosocial intervention and for research on the social functioning of this population are discussed. PMID- 8448977 TI - Recidivism and mental illness: the role of communities. AB - This study examined the impact of community characteristics on rehospitalization of chronically mentally ill (CMI) clients from public psychiatric hospitals in Virginia. The relationship between rehospitalization, often termed recidivism, and community attributes was explained within the theoretical context of community ecology (Hawley 1950). A small area analysis approach that employed path analysis was used to assess the relationship between rehospitalization and selected community variables including: available health care resources, socioeconomic factors, race, presence of psychopathology, and household composition. The path model was estimated and validated using a linear structural relations computer program (LISREL VI). Results reveal female-headed households and socioeconomic status to be significant predictors of rehospitalization. A discussion of implications of the findings for community mental health services delivery and research is provided. PMID- 8448978 TI - HIV and serious mental illness: reducing the risk. AB - Persons with SMI residing in community mental health center group homes received an educational intervention program on HIV/AIDS. As with virtually all such approaches provided for this population, the intervention was generalized from programs used with other populations, for example, users of intravenous drugs, gay men, and adolescents. Assessment of pre- and postintervention knowledge indicated no increase in accurate information. Further, consumers were initially uncertain regarding their risk for HIV infection; this attitude, too, remained unchanged. The research design employed did not compare persons with SMI with a normative sample receiving the same information, and assessed with the same instruments, limiting hypotheses about the generalizability of existing interventions. However, the data seems to suggest its potential inefficacy. Several findings are germane to effective educational intervention techniques. PMID- 8448979 TI - The elusive population: characteristics of attenders versus non-attenders for community mental health center intakes. AB - The present investigation was an attempt to determine characteristics of those who appeared versus those who did not appear for initial intake evaluation appointments at a traditional community mental center. Subjects were 189 individuals contacting the center for service from November of 1989 to April of 1990. Data were collected via self-report questionnaire and blind rating by clinical social workers of presenting problem for diagnostic category. Data analysis involved Chi-square procedures and Analysis of Variance. Those who appeared for initial appointment versus those who did not were differentiated with respect to employment versus unemployment, length of unemployment, tenure at current job, number of jobs in the past year, number of residences in the past year, tenure at current residence and number of marriages. Groups did not differ with respect to age, gender, ethnicity, martial status, income, educational attainment, legal difficulties, public assistance, referral sources, alcohol/drug problems, and a variety of variables related to mental health or treatment history and diagnostic category. Results were interpreted as supporting the hypothesis that attendance was related to recent life stability as opposed to more general demographic and socioeconomic factors and clinically related variables. Implications for increasing treatment utilization, particularly by those who are underserved in community mental health, were discussed. PMID- 8448980 TI - Sexual assault history in a community mental health center clinical population. AB - One hundred and twenty-two adult outpatients, 81 women and 41 men, in a community mental health center responded to a survey of history of sexual assault and abuse. Overall, 48% reported they had been sexually assaulted or abused, 59% of women and 24% of men. Forty-two percent of women and 17% of men reported they had been raped, 27% of women and 7% of men reported attempted rape, and 31% of women and 10% of men reported molestation. Characteristics of assaults and assailants were examined. Implications for training clinicians in the treatment of victims of sexual assault and abuse are discussed. PMID- 8448981 TI - Community psychiatry training for general psychiatry residents: results of a national survey. AB - Through its residency training committee, the American Association of Community Psychiatrists (AACP) surveyed residency training programs throughout the country with the goal of discovering what training is currently in place to prepare psychiatrists for work in "community" or "public" settings which serve traditionally underserved populations. The authors summarize the results of the survey and offer suggestions for further steps needed to improve residency training curricula and to address the need for well qualified psychiatrists to choose careers in community psychiatry. PMID- 8448982 TI - Microbial glutathione S-transferases. PMID- 8448984 TI - Caprine plasma proteinase inhibitors--II. Genetic analysis. AB - 1. Analysis of the inheritances of the variants of five caprine plasma proteinase inhibitor systems in families demonstrated a genetic control of codominant alleles at five loci. 2. The PIA, B, C, D and E proteins are controlled by four (PIA1,2,3,4), three (PIB1,4,0), three (PIC2,3,0), five (PID1,2,3,4,0) and two (PIE1,2) alleles respectively. Null alleles were postulated for the PIB, PIC and PID systems. 3. The frequencies of the alleles differed substantially between the Australian and Texan Angoras and Cashmere breeds of goats. 4. The combined exclusion probability for the five PI systems was as high as 0.82 in the Cashmere breed, indicating the potential of the proteinase inhibitor proteins for parentage control purposes. PMID- 8448983 TI - Caprine plasma proteinase inhibitors--I. Partial characterization. AB - 1. Using two-dimensional electrophoresis (IEF, pH 3.5-6.0 and PAGE, 11.5% T, pH 7.9) the caprine plasma proteinase inhibitors were classified into six distinct classes, designated PIA, PIB, PIC, PID, PIE and PIF. Differentiation of the six inhibitors was based on electrophoretic criteria, their abilities to inhibit bovine trypsin and chymotrypsin and their crossreactions with antisera to human alpha 1-antitrypsin and alpha 1-antichymotrypsin. 2. Polymorphic variants were identified for five of the protein systems (PIA, PIB, PIC, PID and PIE) and the electrophoretic data indicated that the variants were controlled by allelic genes. PIF proteins were poorly resolved and invariant. 3. Treatment of selected plasmas with neuraminidase demonstrated that the microheterogeneity observed in the PIA, PIB, PIC and PID proteins was attributable to sialic acid additions. 4. The inhibitory activities of all six caprine proteinase inhibitors were unaffected by chemical oxidation with chloramine-T. PMID- 8448985 TI - Regulation of liver glucose-6-P dehydrogenase levels in female rats. AB - 1. Gender differences in the dietary regulation of rat liver glucose-6-P dehydrogenase activity, synthesis and mRNA levels were examined. 2. As expected, in normal rats fed a standard chow diet, females have higher G6PD activity than males because they have more G6PD mRNA and therefore a higher rate of G6PD synthesis. 3. In contrast, the decreased dietary induction in female rats is due to a more rapid rate of G6PD degradation rather than a decrease in G6PD mRNA or synthesis. PMID- 8448986 TI - A 27-mer oligonucleotide probe for the detection and measurement of the mRNA for uncoupling protein in brown adipose tissue of different species. AB - 1. Data from rats, cattle, mice, rabbits and humans indicate considerable species heterogeneity in the sequence of the gene coding for the mitochondrial uncoupling protein (UCP) in brown adipose tissue. A 27-base sequence of an exon region of the gene is, however, identical in rats and cattle; in mice, rabbits, and humans this same region shows only a single base difference from the sequence in rats and cattle. 2. A 27-mer oligonucleotide (3'-TGGAAGGGCGACCTGTGGCGGTTTCAG-5') complementary to the conserved region of the rat and cattle UCP genes has been synthesized as a potential probe for UCP mRNA in widely differing species. 3. Northern blots of RNA from rat brown fat showed that the oligonucleotide hybridized with a 1.5 kbase mRNA, indicative of UCP mRNA. No hybridization was observed with RNA from white fat (subcutaneous, internal), liver, kidney, skeletal muscle, heart and brain. Acute cold-exposure of rats and mice led to an increase in UCP mRNA level, while streptozotocin-induced diabetes resulted in a decrease. 4. The oligonucleotide hybridized with a 1.5 (or 1.9) kbase mRNA from brown fat of rats, mice, golden hamsters, Djungarian hamsters, and newborn rabbits, pipistrelle bats, lambs, goats and red deer. 5. The 27-mer oligonucleotide provides a simple probe for UCP mRNA across a wide range of mammals, obviating any need to obtain species-specific cDNAs. PMID- 8448987 TI - Differential properties of phosphatidate phosphohydrolase and diacylglyceride lipase activities in retinal subcellular fractions and rod outer segments. AB - 1. The effect of magnesium and dl-propranolol on phosphatidate phosphohydrolase (PAPase) and diacylglycerol lipase (DGL) activities in isolated rod outer segments (ROS) and of the former on subcellular fractions from bovine retina was investigated. 2. Mg(2+)-independent PAPase activity was found in ROS, whereas in the other subcellular fractions PAPase activities both dependent on and independent of Mg2+ were detected. 3. The membrane-bound PAPase activity was stimulated at low concentrations of Mg2+ and inhibited at higher concentrations. The soluble activity was always stimulated by the ion. 4. dl-Propranolol (1000 microM) exerted a slight stimulatory effect on PAPase in ROS whereas total PAPase activity of microsomal fraction was not affected. 5. Mg2+ (0.2 mM) stimulated DGL activity (30%) whereas it was inhibited at higher concentration. 6. DGL lipase activities, both dependent on and independent of Mg2+, were detected in subcellular fractions of bovine retina. 7. DGL properties in ROS are also described. PMID- 8448988 TI - Lipoprotein metabolism in the frog Rana esculenta. AB - 1. The isoprenoid metabolism of the green frog has been studied, taking into consideration the transport and uptake mechanisms of plasma lipoproteins. 2. The lipoprotein complexes separated on KBr gradient showed six discrete peaks in both sexes. 3. The mechanisms of cellular uptake have been studied by immunological procedures. A molecule homologous to rat LDL receptor, and sharing its ability to bind only specific lipoproteins, has been shown. 4. Homology at mRNA level has also been demonstrated by Northern blot analysis and two different messengers have been shown in both male and female frog. PMID- 8448989 TI - Differences in levels of erythrocyte glutathione and its metabolizing enzyme activities among primates. AB - 1. The levels of erythrocyte glutathione and the activities of its metabolizing enzymes--glutathione peroxidase (GSH-Px), glutathione S-transferase (GST) and glutathione reductase (GR)--were measured in four species of primates: human, rhesus monkey, common marmoset and common tree shrew. 2. There were marked differences in GSH-Px and GST activities among the primates, while GR activity and glutathione level were much less variable. PMID- 8448990 TI - The thymus hypocholesterolemic factor (TphF): a bovine thymic superoxide dismutase active on HMG-CoA reductase. AB - 1. This work describes the further biochemical characterization of a new calf thymus protein (TphF) and its primary structure. 2. The amino acid sequences, obtained after sequence analysis of peptides derived from the endoproteinase Lys C digestion, were subjected to a "Protein Data Bank Search" and were found to be identical with regions of bovine superoxide-dismutase (SOD). 3. These data together with those showing the identical electrophoretic migration of SOD and TphF, their same isoelectric point and their immunoreactivity with anti-SOD antibodies, confirm the similarity of these two proteins. PMID- 8448991 TI - Species difference in hydroperoxide-scavenging enzymes with special reference to glutathione peroxidase in guinea-pigs. AB - 1. As guinea-pigs have been reported to have a markedly low activity of glutathione peroxidase (GSH-Px), the activity of other hydroperoxide-scavenging enzymes was investigated. 2. Catalase activity in guinea-pig tissues was 2-3 times higher than that of mice or rats. 3. Approximately 90% of catalase activity was found in the soluble fraction of guinea-pig liver, suggesting a compensatory role of catalase in removing H2O2 in the cytosol of guinea-pig tissues. 4. In erythrocytes, GSH-Px activity does not differ among rodents. This may reflect the fact that GSH-Px is the sole enzyme in the removal of organic hydroperoxides in erythrocytes where glutathione S-transferase activity is barely detectable. PMID- 8448992 TI - High density lipoprotein metabolism in the horse (Equus caballus). AB - 1. Apolipoprotein A-I dependent lecithin:cholesterol acyl transferase (LCAT) activity was identified in equine lipoprotein deficient plasma (LPDP). 2. LCAT activity showed no breed or sex variation, and was unaltered postprandially. 3. There was no significant cholesteryl ester transfer activity in equine LPDP. 4. Hydrophobic interaction chromatography on phenyl sepharose failed to unmask transfer activity or identify an inhibitor of cholesteryl ester transfer. 5. In 12 Shetland ponies, plasma high density lipoprotein (HDL) concentrations were positively correlated with those of triglyceride, but not with the activities of LCAT, lipoprotein lipase or hepatic lipase. PMID- 8448994 TI - Cardiac and skeletal muscle enzyme levels in hypertensive and aging rats. AB - 1. The activities of glycolytic, fatty acid oxidation and citric acid cycle enzymes were measured in hypertensive and aging rat cardiac and skeletal muscles. 2. Lactate dehydrogenase and beta-hydroxyacyl-CoA dehydrogenase were significantly decreased in hypertensive, but not senescent, cardiac muscle. 3. Total phosphorylase activity was significantly increased in senescent, but not hypertensive, cardiac muscle. 4. In aging rat cardiac and skeletal muscles, calpain II titers increased significantly with age, but in normotensive and hypertensive muscles, the titers showed no significant difference. PMID- 8448993 TI - Comparison of sequences of the 78 kDa gastrin-binding protein and some enzymes involved in fatty acid oxidation. AB - 1. The amino acid sequences of enzymes possessing enoyl-CoA hydratase activity have been aligned with each other and with the sequences of related proteins. 2. The amino acid sequences of enzymes possessing 3-hydroxyacyl-CoA dehydrogenase activity have been similarly aligned. 3. The N-terminal half of the 78 kDa gastrin-binding protein (Baldwin et al., J. biol. Chem. 261, 12,252-12,257, 1986) is related to the enoyl-CoA hydratase family, while the C-terminal half is related to the 3-hydroxyacyl-CoA dehydrogenase family. 4. Evolutionary trees for the two families are presented. PMID- 8448995 TI - Hemocyanin synthesis in the blue crab Callinectes sapidus. AB - 1. The synthesis of hemocyanin in the blue crab, Callinectes sapidus, was investigated by molecular techniques. 2. Polyadenylated mRNA was prepared from the hepatopancreas and translated in rabbit reticulocyte lysate. 3. Translation products were immunoprecipitated with immobilized antihemocyanin IgG. Analysis of the IgG-bound polypeptides by sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed two polypeptides comigrating with authentic Callinectes hemocyanin. 4. A synthetic degenerate 17-mer oligonucleotide mixture derived from the amino acid sequence of the "copper B" binding site of crustacean hemocyanins was prepared. Northern blotting showed the probe to hybridize with one major 2.3 kb RNA species. 5. These results indicate that the hepatopancreas is the site of hemocyanin synthesis. PMID- 8448996 TI - Evidence for alpha and Mu class glutathione S-transferases in a number of fungal species. AB - 1. The glutathione S-transferases of the following fungal species have been affinity purified on glutathione-Sepharose; Yarrowia lipolytica (NCYC825), Sporotrichum thermophile (ATCC16479), Talaromyces emersonii (ATCC26914) and Issatchenkia orientalis (CBS5147 and an isolate provided by Prof. Kumagai, Kyoto University). 2. SDS-PAGE analysis of affinity purified fungal extracts, followed by Western blots with polyclonal antisera to rat GSTs, was performed and indicated the presence of Alpha and Mu class glutathione S-transferases in the fungi immunologically and electrophoretically similar to the rat enzymes. 3. Each extract gave a characteristic affinity-gradient elution pattern on glutathione agarose. PMID- 8448997 TI - Evidence for the role of a cathepsin D-like activity in the release of Gal beta 1 4GlcNAc alpha 2-6sialyltransferase from rat and mouse liver in whole-cell systems. AB - 1. Sialyltransferase is a liver Golgi membrane-bound enzyme that is released from the liver under conditions of experimental inflammation. Previous work showed that the action of a cathepsin D-like proteinase was responsible for release of the enzyme from isolated Golgi membranes. This study shows that the same enzyme is responsible for release of sialyltransferase in whole-cell systems. 2. Gal beta 1-4GlcNAc alpha 2-6sialyltransferase (EC 2.4.99.1) was secreted from slices of rat and mouse liver into the incubation medium with larger amounts of activity being secreted from slices of liver from animals suffering from experimental inflammation. 3. The presence in the incubation medium of the cathepsin D proteinase inhibitor, pepstatin A, at 10(-4) M was sufficient to inhibit the release of sialyltransferase into the medium by about 60% after a 6 hr incubation. 4. The release of albumin and alpha 1 acid glycoprotein from rat liver slices, was not affected by the presence of pepstatin A, indicating that the proteinase inhibitor did not affect the synthesis and secretion of typical secretable proteins by the liver. 5. Intraperitoneal injections of pepstatin A into mice prior to preparation of liver slices also resulted in a significant reduction of the secretion of sialyltransferase into the incubation medium. 6. The results from these studies support the idea that a cathepsin D-like proteinase is responsible for the release of sialyltransferase into the extracellular space in whole cells in the rat and the mouse. PMID- 8448998 TI - Computed tomography in pulmonary tuberous sclerosis. AB - Pulmonary disease is a rare manifestation of tuberous sclerosis. Respiratory symptoms often progress to severe pulmonary insufficiency and death may ensue within a few years of diagnosis. We describe a case where a computerized tomographic scan aided early diagnosis in a patient with spontaneous pneumothorax and subtle, nonspecific changes on a plain x-ray film. PMID- 8448999 TI - Psychopharmacology of nicotine: implications for pharmacotherapy in psychiatry. AB - Cigarette smoking is inconsistent with good health. In psychiatric patients it may also impede recovery through direct CNS effects of nicotine and indirect kinetic effects of enzyme-inducing agents. Psychiatric health professionals should promote smoking cessation with patient education and use of transdermal nicotine coupled with behavioral support. PMID- 8449000 TI - The choice is ours. AB - Unlike their colleagues in all the other states, CSMS physicians are uniquely well positioned for the health care "reform" measures that may be coming down the pike from Washington and/or Hartford, thanks to their proactive organization of the state's only statewide IPA and HMO, CSMS-IPA and M.D. Health Plan. Now in the sixth year of operation, the former has grown to some 3,500 physicians, and the latter to some 75,000 enrollees. Fortunately, the greater than budgeted utilization experienced earlier in 1992 has begun to resolve, and the withhold will be returned to 20% in January 1993. But to assure future security, the organizations have determined that such swings in utilization must be made less likely and less severe by individual physicians being informed at the local level where they stand with respect to preestablished clinical norms and to the performance of their peers. PMID- 8449001 TI - Improving health-care costs with minimal compromise. PMID- 8449002 TI - Pinched nerves and signature signs. PMID- 8449003 TI - Cost of health care--the truth. PMID- 8449004 TI - Real reform or just tinkering? PMID- 8449005 TI - Ends and means in organ transplantation: the anencephalic donor. PMID- 8449006 TI - Cooperation and compromise. PMID- 8449007 TI - Defensive medicine. PMID- 8449008 TI - Interactive effects of basic fibroblast growth factor and heparin on bone in 21 day fetal rat calvariae. AB - We examined the interactive effects of heparin and basic fibroblast growth factor (bFGF) on collagen and DNA synthesis in 21-day fetal rat calvariae. In calvariae treated for 24h with heparin (25 micrograms/ml), a significant inhibition of methyl [3H]thymidine (Tdr) incorporation into DNA and [3H]proline labeling of collagenase-digestible protein (CDP) occurred compared to control. Treatment for 24h with bFGF (10(-11) to 10(-9) M) caused a stimulation of Tdr incorporation. With 96h treatment, bFGF (10(-9) M) inhibited CDP labeling by 61%. Basic FGF in combination with heparin overcame the inhibitory effects of heparin on Tdr incorporation. The combination of bFGF plus heparin produced an even greater inhibition of CDP labeling than either effector alone. To assess the role of prostaglandin E2 (PGE2) in moderating the effects of bFGF, calvariae were treated with bFGF in the presence and absence of indomethacin (10(-6) M), an inhibitor of PGE2 production. Indomethacin did not alter the effects of bFGF on Tdr or CDP. We conclude that heparin and bFGF do interact to modulate collagen synthesis in bone via a PGE2-independent mechanism. PMID- 8449009 TI - Trends in breast cancer treatment in Connecticut. AB - Data from the population-based Connecticut Tumor Registry showed an increase in partial mastectomy (PM) from 18.9% for local-stage breast cancers diagnosed in 1983 to 47.3% for those diagnosed in 1990, with no change in axillary dissection. For local-stage cancers 4 cm or smaller in size that received PM, axillary dissection increased from 39.2% in 1983 to 60.8% in 1990, with larger increases for cases < 50 and 50-59 years old, while radiotherapy increased mainly for cases 70-79 and > 80 years old. Among regional-stage cases with positive nodes (but no extension to skin or beyond the breast tissue) and 4 cm or smaller in size, PM increased from 9.4% to 29.1%, but remained lower than that among local-stage cancers. Continued monitoring is needed to assess the full impact of the 1990 NIH Consensus Conference Panel's recommendations for the treatment of early-stage breast cancer. PMID- 8449010 TI - The maternity home for adolescents: a concept from the past fulfilling a contemporary need. AB - Maternity homes endure as an important means of imparting total care to some of today's homeless pregnant girls. This description of one such program is intended to serve as a model for the modern maternity residence for teens. Homelessness is a major complication of adolescent pregnancy. We believe that a supervised group home can be utilized to provide comprehensive care for homeless pregnant young women. We compiled data over the past six years (1986-91) from a residential facility for pregnant teenagers and their newborns, where the principal coauthor serves as voluntary medical director. During this period, 285 homeless adolescent females were admitted to the facility; their average age was 15.75 years, and 50% were white, 37% were African-American, and 13% were latino. All of the residents who were assigned private bedrooms, received prenatal care, accredited on-site schooling, family-life education, social services, dietary counseling, day-care services, and meals. The average length of stay was four months. The average birth weight was 6.62 pounds. Sixteen percent of the newborns were placed for adoption. Data from 1987 through 1989 showed that 74% of the girls had either attained their educational or vocational objectives or were pursuing those goals at the time of discharge. Achievements included high school graduation, job training, and college attendance. We conclude that this type of residential environment provides a wide range of resources beneficial to the homeless pregnant teen and her baby. PMID- 8449011 TI - On death and dying. AB - Over a six-month period from February to August, 1992, one Hospice team cared for 134 patients who died. The terminal course of each patient was evaluated in terms of pain control, fear of death, and denial of death. Results were tabulated and conclusions were drawn. PMID- 8449012 TI - An historical review of rupture of the heart. PMID- 8449013 TI - Termination of second trimester pregnancy with sulprostone and mifepristone: a randomized double-blind placebo-controlled trial. AB - A prospective randomized double-blind placebo-controlled trial was conducted in 13 subjects to find out whether mifepristone treatment could facilitate termination of second trimester pregnancy by sulprostone. The women received either 600 mg oral mifepristone or placebo tablets 36 hours before the administration of intramuscular sulprostone 0.5 mg every 6 hours. The median interval between the administration of sulprostone and abortion in the mifepristone group (4.6 hours) was significantly shorter than that in the placebo group (20 hours). The amount of sulprostone required was also significantly less in the mifepristone group. There was no significant difference in the incidence of side effects or analgesic requirement between the two groups. We conclude that oral mifepristone is useful in facilitating termination of second trimester pregnancies by sulprostone. PMID- 8449014 TI - A randomized comparative open study of the effects of two oral contraceptives, Triphasil and Ortho 7/7/7, on lipid metabolism. AB - This study assessed serum lipid, lipoprotein and apolipoprotein changes during one year in 3 groups of nonsmoking women: 1) Triphasil(R); 2) Ortho(R) 7/7/7; 3) Controls. Both oral contraceptives contain the estrogen, ethinyl estradiol(EE), in combination with a progestin in three different ratios during each cycle. The progestin in Triphasil is d-norgestrel, as the dl-racemate norgestrel (NG), whereas that in Ortho 7/7/7 is norethindrone(NE). Total plasma triglycerides were elevated significantly from baseline (p < 0.001) with Ortho 7/7/7 at 3, 6 and 12 months, but only at 3 months with Triphasil, p = 0.047. Triglycerides were elevated in the LDL fraction with Ortho 7/7/7 at 3 months (p = 0.001), 6 months (p = 0.018) and 12 months (p = 0.010). In contrast, LDL triglycerides were not significantly elevated with Triphasil. Similarly, IDL triglycerides were elevated only in the Ortho 7/7/7 group at 6 months (p = 0.002) and 12 months (p = 0.001). Plasma cholesterol was elevated only in the Ortho 7/7/7 group at 3, 6 and 12 months with p values of 0.009, 0.005 and 0.010, respectively. Cholesterol in the LDL fraction was elevated with Ortho 7/7/7 at 12 months (p = 0.002). Plasma apolipoprotein B (apo B) increased at least 24% from baseline for both the Triphasil and Ortho 7/7/7 groups at 3 and 12 months (p < 0.001). However, at 6 months, apolipoprotein B increased only 17.7% (p = 0.008) with Triphasil compared to 29.7% (p < 0.001) with Ortho 7/7/7 at 6 months. Apo B was increased (p < 0.001) in LDL with Triphasil at 3 months only, whereas LDL apo B was increased at 3, 6 and 12 months with Ortho 7/7/7 (p < 0.001, p = 0.020 and p = 0.012, respectively). Apo B increased dramatically in the IDL fraction of both oral contraceptive user populations, with the range of increases being between 48% and 87% during the year (p < 0.001 at all times). Significant elevations in VLDL apo B ranged from 71% to 106% (p < 0.001) with Triphasil and from 42.4% (p < 0.005) to 72.6% (p < 0.001) with Ortho 7/7/7. In conclusion, norethindrone- and dl norgestrel-formulations have divergent effects on several components of plasma lipoprotein and lipid metabolism, but both products increase plasma and IDL apo B. PMID- 8449015 TI - Effects of Norplant contraceptive subdermal implants on serum lipids and lipoproteins. AB - A longitudinal, short-term study of women using NORPLANT (levonorgestrel implants) was conducted. Cholesterol content of the major lipoproteins along with total cholesterol and triglycerides were measured in fasting blood samples from 32 women volunteers. Results for lipids and lipoproteins determined 6 and 12 months post-NORPLANT insertion were compared with values obtained for samples taken just before implantation. Total serum triglycerides was significantly reduced (p < 0.01) from 1.14 +/- 0.44mmol/l (mean +/- SD) to 0.89 +/- 0.25mmol/l at six and to 0.89 +/- 0.34mmol/l at twelve months post-insertion. Serum total cholesterol was 3.97 +/- 0.53mmol/l at the time of insertion while at six and twelve months post-insertion, they were 3.65 +/- 0.49mmol/l and 3.56 +/- 0.71mmol/l, respectively. These changes in values from the time of insertion to twelve months, were statistically significant (P < 0.02). As regards lipoprotein fractions, high density lipoprotein-cholesterol (HDL-chol) exhibited statistically significant reduction (P < 0.001) from 1.38 +/- 0.34 mmol/l to 0.71 +/- 0.30 mmol/l (mean +/- SD) six months post-insertion. Although the value had improved to 1.14 +/- 0.38mmol/l by twelve months, the value was still significantly different from the pre-insertion value. The low density lipoprotein cholesterol (LDL-chol) had a mean value (+/- SD) of 2.08 +/- 0.45 mmol/l at the time of insertion. This was significantly elevated (P < 0.001) at six months to 2.54 +/- 0.48mmol/l (mean +/- SD). The twelve-month post-insertion value of LDL chol (2.02 +/- 0.79) was similar to the pre-insertion value. The shift in HDL cholesterol and LDL-cholesterol within six months followed by a virtual return to the pre-insertion values may represent only a transient change in metabolism of lipids and lipoproteins consequent upon NORPLANT contraception. PMID- 8449017 TI - Evaluation of the clinical performance of a levonorgestrel-releasing IUD, up to seven years of use, in Campinas, Brazil. AB - The clinical performance of a levonorgestrel IUD, releasing 20 mcg/day, used by 293 women at the Family Planning Clinic of the State University of Campinas, was evaluated up to the end of the seventh year of use. No pregnancies occurred in 899 women-years of observation. The cumulative removal rate for amenorrhea or severe hypomenorrhea was 15.7 per 100 women at seven years. The expulsion rate was within ranges observed with copper IUDs in the same clinic. The continuation rate was 49.5% at three years and 23.7 at seven years. The cumulative loss to follow-up rate was 13.7% at seven years. The effectiveness, good continuation rate, and reduction of the amount of blood loss make this device appropriate to be offered to Brazilian women, as an additional contraceptive option. PMID- 8449016 TI - Oral contraceptives and reproductive factors in multiple sclerosis incidence. AB - Data from the Oxford.FPA prospective study show that oral contraceptive use and pregnancy have no discernible effect on the risk of developing multiple sclerosis (MS). Women of parity 0-2 developed MS twice as often as women of parity 3 or more but the difference did not reach statistical significance. Smoking may be a risk factor for developing MS. A nested case-control analysis did not identify any associations between MS onset and preceding illnesses. PMID- 8449018 TI - A multicentre comparative study of serum lipids and apolipoproteins in long-term users of DMPA and a control group of IUD users. World Health Organization. Task Force on Long-Acting Systemic Agents for Fertility Regulation Special Programme of Research, Development and Research Training in Human Reproduction. AB - A clinical trial was conducted in three centres to assess the effects of long term use of the injectable contraceptive depot-medroxyprogesterone acetate (DMPA) on lipid metabolism. Fifty women who had used DMPA at a dose of 150 mg every three months for 3 to 9 years were recruited in Bangkok, Christchurch and Mexico City. They were compared to a control group of 120 IUD users. Total cholesterol, LDL-cholesterol, HDL-cholesterol, total triglycerides, apolipoproteins AI, AII and B were measured throughout one injection interval. Significant findings differed between centres. Compared to their own centre controls, DMPA users in Bangkok had higher LDL-cholesterol levels; those in Christchurch had lower HDL cholesterol, apolipoprotein (apo) AI and apo AI/B ratio and higher apo B levels; those in Mexico City had a lower apo AI/B ratio. Further changes were observed during the injection interval, some of which were correlated to changes in serum MPA levels. It is concluded that long-term use of DMPA induces moderate changes in lipid metabolism which are unfavourable in terms of risk for atherosclerosis. This should be borne in mind when weighing the overall risks and benefits of this contraceptive method for a potential user. PMID- 8449020 TI - Release kinetics of 3-keto-desogestrel from contraceptive implants (Implanon) in dogs: comparison with in vitro data. AB - Ethylene-vinyl acetate (EVA) polymeric contraceptive implants (Implanon) containing 3-keto-desogestrel have been prepared aiming at an in vitro initial release rate of 60 micrograms 3-keto-desogestrel/day. These implants are designed to have an intended life-time of 2 years. During a 3-year period, the release of these implants was studied in 4 dogs after subdermal insertion, using plasma clearance of 3-keto-desogestrel assessed after intravenous administration of 3 keto-desogestrel and steady state plasma levels of 3-keto-desogestrel. The mean plasma level of 3-keto-desogestrel decreased gradually during the first year of the study, viz. from 1.64 nmol/1 at 7 days after implantation to 0.69 nmol/l after one year. At the end of the second year, the level had decreased further to 0.45 nmol/l while after 3 years, the mean 3-keto-desogestrel plasma level was 0.42 nmol/l. The calculated mean daily release of 3-keto-desogestrel decreased during the first year from 70 micrograms/day to 30 micrograms/day. During the second and third year, the decrease in release rate was much less, viz. going from 30 micrograms/day to 28 micrograms/day and from 28 micrograms/day to 25 micrograms/day, respectively. This indicates a much more constant release during the second and third year of the study. The calculated cumulative amount of 3 keto-desogestrel released from the implant during the dog study was 34.0 mg. Based on the initial amount of 3-keto-desogestrel in the implant of 68.3 mg, the remaining amount in the implants at termination of the study should be approximately 34.3 mg. Actually, the mean remaining amount of 3-keto-desogestrel was 33.8 mg, which is in very close agreement with the calculated value. Implants from the same batch as used in the in vivo study were also analyzed for the in vitro release at regular times during the 3-year study period. After one year, the in vitro release rate was about 43 micrograms/day whereas this release rate was 33 and 27 micrograms/day after 2 and 3 years, respectively. Although the in vitro set-up constantly gave a somewhat higher release in comparison with the in vivo release, it is apparent that the in vitro procedure is valuable for prediction of the in vivo release characteristics of the implant. There were no indications for 3-keto-desogestrel accumulation at the implantation site. No local irritations were seen and the animals had no discomfort at all.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8449019 TI - Preliminary experience with Norplant in an inner city population. AB - Norplant, the five-year subdermal contraceptive system, is the first implantable contraceptive method approved for general use in the United States. We describe the preliminary experiences of 246 U.S. women who accepted Norplant between April, 1991 and September, 1991. Norplant was well accepted among this diverse general population. Intensive counselling about side effects, especially menstrual changes, is crucial for patient satisfaction. Although 48% of acceptors experienced menstrual cycle changes and 70% experienced at least one side effect, phone calls and unscheduled visits for problems were infrequent. Adequate counselling about side effects obviates the need for a routine follow-up visit one month after insertion. PMID- 8449021 TI - An analysis of two fibril systems in the mammalian vitreous. AB - The vitreous of most mammals contains low concentrations of three polymeric macromolecules, collagen, hyaluronan and beaded fibrils. To determine whether the beaded fibrils may have a localized function, or whether all three of these polymers could contribute to the structure and/or strength of the vitreous gel, the distribution of collagen and beaded fibrils in the central and cortical regions of the bovine vitreous was studied. The polymers were separated by isopycnic centrifugation and analyzed to determine the protein ratios. Both collagen and beaded fibrils are present in each region, but the concentration of the beaded fibril is greatest in the posterior cortical volume. PMID- 8449022 TI - Glutathione isopropyl ester (YM737) inhibits the progression of X-ray-induced cataract in rats. AB - The effect of glutathione (GSH) isopropyl ester on the progression of X-ray induced cataract was investigated in rats. Intraperitoneal administration of 20 mg/kg GSH isopropyl ester, three times weekly, 1 day after a single irradiation dose delayed the progression of X-ray-induced cataracts significantly. The amount of non-protein SH groups and the Na+/K+ ratio in the lenses of drug-treated rats were maintained at the normal levels even 27 weeks after irradiation. Posttreatment with the drug resulted in a significantly lower level of malondialdehyde in the irradiated lenses than in the nontreated lenses. When 500 mg/kg GSH-isopropyl ester was administered by i.p. injection to normal rats, the GSH-ester was detected in plasma and aqueous humor after 15 min. In the lenses of the GSH-isopropyl ester-injected rats, the GSH level was 120% of that in the non treated rats after 4 h, suggesting that GSH-isopropyl ester is transported from the aqueous humor to the lens and there converted to GSH after about 4 h. Our observations lead us to conclude that the delay of X-ray-induced lens opacity progression is due to maintenance of normal lenticular GSH levels achieved by post-irradiation administration of GSH-isopropyl ester. However, continuous administration of 100 mg/kg after irradiation had no effect on the progression of cataracts induced by X-rays. PMID- 8449023 TI - Measuring progression of lens opacities for longitudinal studies. AB - A number of classifications schemes for the grading of lens opacities have been developed but none of them have been examined for reliability and validity in prospective or longitudinal studies. The purpose of this study was to develop and test a method for determining progression which was sufficiently sensitive to true change and insensitive to measurement error. The method consists of assessing various sources of measurement error, determining the likely magnitude of the error, and setting boundaries for changes in opacification which incorporate this error. Measurement error was assessed in 203 nuclear lens photographs graded using a decimal system and 136 cortical lens photographs graded in 1/16th area. 95% confidence intervals were calculated of the distribution of differences between photographs and graders and the width of this intervals defined as measurement error. The magnitude of the measurement error was +/- 0.7 units for nuclear opacities and +/- 2/16 for cortical opacities. The utility of this approach was tested in a series of 84 clinic patients followed at irregular intervals for up to 3 years. Only one eye showed "improvement" and progression rates ranged from 1.8 to 5.5% for nuclear opacities and 0 to 7.4% for cortical opacities in this clinic-based series. This approach appears to be useful for discarding noise and enabling the assessment of progression for use in longitudinal studies. PMID- 8449024 TI - Morphometric analysis of human retinal pigment epithelium: correlation with age and location. AB - Flat bleached preparations of retinal pigment epithelial (RPE) cells from foveal, temporal posterior pole, and temporal equatorial fundus locations of 20 normal human eyes from donors age ranked from 13 to 96 years were analyzed for density, and 10 were analyzed for area, hexagonality and polymegathism. These factors were related to fundus locations and age. Foveal RPE cells were significantly more dense and more hexagonal in eyes from younger donors. Loss of hexagonality in the fovea, but not elsewhere, was correlated with increasing age. As the eye ages, foveal RPE cells selectively lose unique morphologic characteristics and resemble nonfoveal cells. These morphologic changes resemble other pathologic features of age-related degeneration in their proclivity for the fovea and posterior pole. PMID- 8449025 TI - Collagens in the aged human macular sclera. AB - Scleral tissue from the region of the human macula was studied by the immunogold labeling technique (cryoultramicrotomy and LR white resin embedding) in an attempt to identify the fine structural distribution of collagen types I-VI. Labeling of the striated collagen fibrils suggested colocalisation of collagen types I, III and V with type V occurring at the fibril surface. Both types V and VI collagen were localised to filamentous strands in the interfibrillar matrix. Collagen types II and IV were absent from the scleral stroma. PMID- 8449026 TI - Muscarinic cholinoceptors in native and cultured human corneal endothelium. AB - Specific and high affinity binding of the potent muscarinic cholinergic antagonist, [3H]quinuclidinylbenzilate ([3H]QNB) was observed using intact native and cultured adult human corneal endothelium (HCE). Specific binding was proportional to radioligand concentration between 0.03 and 5 nM, indicating a maximal binding capacity (Bmax) of 130 fmol of [3H]QNB/mg protein and a dissociation constant (Kd) of 0.3 nM. Atropine competed effectively with [3H]QNB for binding sites; requiring 3 nM to inhibit 50% of the binding of 1 nM [3H]QNB. Carbachol also competed with [3H]QNB at higher concentrations, but nicotine did not affect [3H]QNB binding at levels up to 1 nM. [3H]QNB binding was also observed in cultured cells of adult human, rabbit, and bovine corneal endothelium. Native and cultured HCE were affinity labelled using tritium labelled propylbenzilylcholine mustard (PBCM). Separation of the proteins in affinity labelled native and cultured tissue by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) showed that only one protein in each preparation, of 60 and 55 kilodaltons (kDa), respectively, was specifically radiolabelled. These data indicate that the corneal endothelium of human and several animal species exhibit muscarinic cholinoceptors. PMID- 8449027 TI - Melatonin does not increase IOP significantly in rabbits. AB - New Zealand white rabbits have a circadian rhythm of intraocular pressure; pressure is higher during the dark than during the light. We explored the possibility that the dark phase increase of serum and/or ocular melatonin plays a role in regulating the rhythm of intraocular pressure. Exogenous melatonin was delivered by four routes: topical application (0.1 and 10 micrograms), intravenous injection (1 microgram), intravitreal injection (9 micrograms) and intra-arterial infusion (50 ng and 1 microgram). Melatonin delivered by these routes did not increase intraocular pressure. We also measured the concentration of melatonin in the aqueous after unilateral intra-arterial infusion to confirm that melatonin delivered by this route reached the eye. The concentration was 419 +/- 99 and 109 +/- 17 pg/ml (n = 8, p < 0.025) in the ipsilateral and contralateral eyes, respectively. The concentration of melatonin in the aqueous after intra-arterial infusion of saline was less than the sensitivity of the assay (< 16 pg/ml, n = 6). The results of these experiments indicate that melatonin does not increase IOP significantly under the experimental conditions employed in this study. PMID- 8449028 TI - NCAM of the mammalian lens. AB - NCAM is present in the plasma membranes of human and rat lens epithelial cells and superficial fiber cells. The predominant isoform in epithelial cells is NCAM 140, while NCAM 120 appears only in the superficial fiber cells. The immunofluorescence patterns are consistent with a decreasing concentration of NCAM associated with fiber cell differentiation. PMID- 8449029 TI - Treatment of autoimmune uveoretinitis in the rat with rapamycin, an inhibitor of lymphocyte growth factor signal transduction. AB - Rapamycin (RAPA) is a macrolide antibiotic with unique immunosuppressive properties. RAPA inhibits T-cell function by interfering with IL-2 and IL-4 signal transduction. It does not prevent IL-2 production or IL-2R expression. The efficacy of RAPA in the treatment of autoimmune diseases was evaluated using the experimental autoimmune uveoretinitis (EAU) model. EAU was actively induced in Lewis rats by immunization with S-antigen in Hunter's adjuvant. RAPA and control vehicle were administered by continuous intravenous infusion over a 14 day period by miniosmotic pump. RAPA treatment initiated on the day of immunization or 7 days later was found to efficiently inhibit EAU induction. The minimal effective dose was 0.1 mg/kg/d. EAU inhibition was correlated with reduced number of cells in the immunization site draining lymph nodes, as well as with a shift and lowering of the peak of the lymphocyte proliferative response curve. The anti-S antigen antibody response was delayed by 3 days under RAPA treatment and the serum levels lowered in a dose dependent manner. An initial body weight loss was observed during the first week of drug administration, but there was a normal weight gain afterward. PMID- 8449030 TI - Damage to the rainbow trout (Oncorhyncus mykiss) lens following an acute dose of UVB. AB - Rainbow trout (Oncorhynchus mykiss) were used to model the solar radiation induced cataract that occurs in hatchery-reared lake trout (Salvelinus namaycush). Rainbow trout eyes were exposed to wideband predominantly UVB radiant energy from a filtered 1000W xenon source. Lenticular damage was assessed and classified and comeal damage noted. Lenticular threshold radiant exposure was 0.48 J.cm-2 which is in the same range as the mammalian lens. Permanent lenticular damage occurred at radiant exposure levels approximately twice the threshold for lenticular radiant exposure (also similar to the mammalian response). Slit-lamp and scanning electron microscopical results support the theory of post-exposure anterior subcapsular epithelial cell damage, lens fibre swelling, and eventual rupture, leading to areas of lower refractive index in the anterior subcapsular region of the lens. PMID- 8449031 TI - Genome size and qualitative and quantitative characteristics of C-heterochromatic DNA in Eulemur species and in a viable hybrid. AB - The amounts of nuclear DNA and the AT and GC content of four Eulemur (Prosimii, Lemuridae) species and of an E. coronatus x E. macaco hybrid were measured by flow cytometry in peripheral blood leukocytes, following propidium iodide, Hoechst 33258, and mithramycin staining. Hoechst 33258 and mithramycin were also used to evaluate the base composition of genomic DNA in the chromosomes. The amount of DNA resisting C-banding pretreatment (C-heterochromatic DNA) was measured in metaphase chromosomes by static fluorometry. The genome of E. coronatus was significantly larger than the genomes of all other species examined, due to a higher content of pericentromeric, mainly GC-rich, heterochromatic DNA. The restriction banding patterns produced by BamHI digestion and ethidium bromide staining on extracted DNA were studied in the hybrid and its parental species (E. coronatus and E. macaco). The restriction banding pattern of the sole E. coronatus individual showed two bands which were repeated in the restriction banding pattern of the hybrid. The qualitative and quantitative differences of C-heterochromatic DNA in E. coronatus confirm the "splitting" processes and the phylogenetic relationships in the genus Eulemur suggested by Jung et al. (1992) on the basis of the restriction banding patterns produced by endonuclease digestion. PMID- 8449032 TI - Analysis of chiasma frequency and first meiotic segregation in a human male reciprocal translocation heterozygote, t(1;11)(p36.3;q13.1), using fluorescence in situ hybridisation. AB - In this study we have used a testicular biopsy from a human male with a 46,XY,t(1;11)(p36.3;q13.1) karyotype. Fluorescence in situ hybridisation with whole chromosome libraries and paracentromeric probes were applied to identify normal and derived chromosomes 1 and 11 in both first metaphase (MI) and second metaphase (MII) cells. The chiasma frequency distribution was established in the quadrivalent. A large proportion of MI cells was found to have at least one interstitial chiasma, resulting at MII in dimorphic chromosomes bearing one normal and one translocated chromatid. Alternate, adjacent I, adjacent II, and 3:1 products were all identified at MII. More than half of the cells analysed could not be assigned to a single segregation category because of the presence of interstitial chiasmata. Such MII cells could have arisen from either alternate or adjacent I segregation. We also calculated the proportion of sperm expected to be normal, balanced, and unbalanced. The latter data are in agreement with the results reported by Spriggs et al. (1992), who karyotyped sperm from the same individual. PMID- 8449033 TI - Fluorescence in situ hybridization combined with immunohistochemistry for highly sensitive detection of chromosome 1 aberrations in neuroblastoma. AB - The development and application of a highly sensitive double-target fluorescence in situ hybridization (FISH) method in combination with immunohistochemistry for detection of chromosome 1 abnormalities in interphase nuclei of neuroblastoma samples is reported. An alpha-satellite probe specific for chromosome 1 and a VNTR probe that hybridizes to chromosome band 1p36.3 were hybridized to GD2 prestained neuroblastoma cells in double-target FISH experiments. The ratio of intact to deleted chromosome 1 homologs in the neuroblastoma cells was assessed. To demonstrate the reliability of the method described, four selected samples derived from different neuroblastoma stages are presented. FISH results correlated well with data obtained by conventional cytogenetic procedures. The technique described allows sensitive detection of chromosome 1 abnormalities in interphase nuclei and enables partial cytogenetic analysis of nondividing cells with a defined immunological phenotype. PMID- 8449034 TI - In situ hybridization applied to Waardenburg syndrome. AB - Multilocus linkage analysis has suggested that the Waardenburg syndrome type 1 (WS1) locus is flanked by placental alkaline phosphatase (ALPP) and fibronectin 1 (FN1). We used fluorescence in situ hybridization (FISH) to map ALPI (intestinal alkaline phosphatase) to 2q36.3-q37.1 and FN1 to 2q34. FISH also showed that a WS1 patient with a de novo interstitial deletion of 2q35-q36.1 retained both API and FN1 on the deleted chromosome. The human PAX3 gene has been shown previously to be mutated in at least two WS1 patients. We mapped a PCR product from the PAX3 gene to 2q35 and found it was absent in the deleted chromosome. Thus, our FISH mapping results confirm the conclusions from previous linkage analysis and support the conclusion that mutation of the PAX3 gene can cause Waardenburg syndrome. PMID- 8449035 TI - Confirmation of 15q26.1 as the site of the FES protooncogene by fluorescence in situ hybridization. AB - The FES oncogene was previously localized to human chromosome 15 by analysis of mouse x human somatic cell hybrids and to 15q26 by in situ hybridization of a radioactively labeled probe. In the present study, using fluorescence in situ hybridization, we have determined the precise map position of FES at 15q26.1. PMID- 8449036 TI - Assignment of human B2-1 gene (D17S811E) to chromosome 17qter by PCR analysis of somatic cell hybrids and fluorescence in situ hybridization. AB - The human gene B2-1 has significant homology to the yeast gene SEC7. By PCR analysis of a human x rodent hybrid panel, the B2-1 gene was assigned to chromosome 17. Fluorescence in situ hybridization localized the gene to 17qter. PMID- 8449037 TI - Assignment of the human lipoprotein lipase (LPL) gene to chromosome band 8p22. AB - The lipoprotein lipase gene (LPL) was mapped to chromosome band 8p22 by in situ hybridization to human chromosomes. This confirms the status of this assignment, which was still provisional. PMID- 8449038 TI - Growth and development of 39,X mouse embryos at mid-gestation. AB - We examined the growth and development of XO embryos at mid-gestation (day 10) by assessing crown-rump length, head length, somite number, and morphological score (Van Maele-Fabry et al., 1990), using an XO mouse colony established from the Jcl/ICR strain. Contrary to expectation, there were no differences between the XO and XX embryos in any parameter measured. Also, no particular region was specifically retarded in XO embryos during development. We therefore concluded that the growth and development of XO embryos were not retarded when compared with their XX littermates at day 10 of gestation. PMID- 8449039 TI - Mapping of the KREV1 transformation suppressor gene and its pseudogene (KREV1P) to human chromosome 1p13.3 and 14q24.3, respectively, by fluorescence in situ hybridization. AB - The chromosomal location of the transformation suppressor gene KREV1 and its pseudogene (KREV1P) on R-banded human prometaphase chromosomes was determined by fluorescence in situ hybridization. The KREV1 gene mapped to chromosome 1p13.3, whereas the KREV1P pseudogene mapped to 14q24.3. Our results substantiate the previous mapping data of Rousseau-Merck et al. (1990) and further confine the position of the RAP1A/KREV1 gene to a narrower region. PMID- 8449040 TI - Somatic cell mapping of omega and trophoblast interferon genes to bovine syntenic group U18 and in situ localization to chromosome 8. AB - Bovine omega (IFNW) and trophoblast (IFNT) interferon genes were assigned to bovine syntenic group U18 by somatic cell genetics. Fluorescent in situ hybridization subsequently localized these genes to bovine chromosome 8 band 15. This assignment conflicts with a previous assignment of U17 genes to the same chromosome. PMID- 8449041 TI - Chromosomal localization of the human ciliary neurotrophic factor gene (CNTF) to 11q12 by fluorescence in situ hybridization. AB - The human gene for ciliary neurotrophic factor (CNTF) was previously assigned to chromosome 11 by analysis of a panel of somatic cell hybrids. We isolated cosmid clones containing the CNTF gene from an arrayed-chromosome specific library and used fluorescent in situ hybridization to regionally localize the human CNTF gene on chromosome 11. The gene maps at an FLpter of 0.46, corresponding to a cytogenetic band position of 11q12.2. PMID- 8449042 TI - T(In1;5)44H, a complex mouse chromosomal rearrangement with a phenotypic effect. AB - A complex murine chromosomal rearrangement, T(In1;5)44H, was recovered after 5 Gy + 5 Gy (given 24 h apart) spermatogonial X-irradiation. T44H is a paracentric inversion of most of Chromosome (Chr) 1 (1A1-1H6), followed by splitting of the inverted segment through a reciprocal translocation with Chr 5, the latter breakpoints being in 1C2 and 5F. Linkage tests have shown that the probable order on Chr 1 is fz-ln-T44H with 2.4 +/- 2.4 crossover units between ln and T44H. On Chr 5 the probable order is W-T44H-go-bf with 7.1 +/- 4.9 crossover units between T44H and go. All heterozygotes show a marked dilution of coat colour. Heterozygotes of both sexes are fertile, producing small litters with a marked shortage of T44H carriers. The number of live embryos produced from female carriers is significantly lower than from males. Despite the complex nature of the rearrangement, complete chromosome pairing and chiasma formation occur regularly at meiosis. Depending on the strands involved, this leads to the production of either one or two dicentric chromatids per spermatocyte, and their disjunctional fate can be followed into metaphase II. Analysis of chromatid classes at this stage suggests reasons for both the high embryonic mortality and the shortage of liveborn T44H carriers. PMID- 8449043 TI - Multiple and sensitive fluorescence in situ hybridization with rhodamine-, fluorescein-, and coumarin-labeled DNAs. AB - We have tested the use of several newly developed red, green, and blue fluorescent dUTPs in direct, multiple, and sensitive fluorescence in situ hybridization procedures. Among the ones tested, the tetramethylrhodamine-dUTP proved to give the best sensitivity; using conventional epifluorescence microscopy, cosmids could be visualized with a hybridization efficiency of 90%. Fluorescein-dUTP permitted visual cosmid detection with 50% efficiency, and, to the human eye, the green signals appeared less bright. With a blue fluorescent coumarin-labeled dUTP, only highly repetitive target sequences could be visualized directly. Imaging with a cooled CCD (charged coupled device) camera for prolonged integration times permitted localization of small targets using probes labeled with red and green fluorochromes. Visualization of a 1.8-kb single copy sequence with a rhodamine-labeled cDNA proved feasible. The strategy of identifying hybridization sites with multiple colors was successfully applied for multiple hybridizations to repetitive and unique targets, using the red and green labels directly and the biotin label indirectly with one layer of avidin coumarin. PMID- 8449044 TI - Characteristics influencing the effective administration of drugs as inhalation aerosols. PMID- 8449045 TI - Bacteremic pneumococcal pneumonia mortality rate. Is it really different in Sweden? PMID- 8449046 TI - The role of thrombosis in pulmonary hypertension. PMID- 8449047 TI - Emergency department management of life-threatening asthma. Are nebulizers obsolete? PMID- 8449048 TI - A stitch in time saves lives. PMID- 8449049 TI - Emergency department treatment of severe asthma. Metered-dose inhaler plus holding chamber is equivalent in effectiveness to nebulizer. AB - STUDY OBJECTIVE: To compare the effectiveness of administration of albuterol by nebulizer or by a metered-dose inhaler having a holding chamber attachment (hereafter "inhaler") for treatment of acute asthma in an emergency department (ED). DESIGN: A randomized, double-blind, placebo-controlled intervention study conducted at two sites. SETTING: The EDs of a large municipal hospital and a university teaching hospital. PATIENTS: Thirty-five patients 10 to 45 years of age seeking treatment at an ED for acute asthma. INTERVENTIONS: Patients were randomly assigned to receive either albuterol by nebulizer plus placebo by inhaler (n = 20) or albuterol by inhaler plus placebo by nebulizer (n = 15). The dose was repeated every 30 min until the FEV1 was at least 80 percent of predicted, the patient became asymptomatic, or 6 doses had been given. MEASUREMENTS AND RESULTS: All references in this article to spirometric measurements of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and peak expiratory flow rate (PEFR) represent percentages of the predicted normal value. No significant (p > 0.58) differences occurred in baseline mean FEV1, FVC, or PEFR for the two groups. For both groups, significant improvement occurred in mean FEV1 at 30 min (p < 0.02) and at 60 min (p < 0.02), and in maximum mean FEV1 (p < 0.001). However, no significant (p > 0.6) differences occurred between groups in mean FEV1, FVC, or PEFR at 30 and 60 min, or in maximum improvement attained. The sample size was sufficiently large to detect a 12 percent difference in improvement with a power of 90 percent. Thirty three of 35 patients were treated successfully with the study protocol, became asymptomatic, and were discharged home. One patient from each group required further treatment. CONCLUSIONS: There was no detectable difference in effectiveness of albuterol administered by nebulizer or the inhaler system for treatment of acute asthma. There was no detectable difference in effectiveness of albuterol administered by nebulizer or the inhaler system for the treatment of acute asthma when the dose was titrated to clinical response. When compared with nebulizer, the metered-dose inhaler with holding chamber delivers a full dose of albuterol more quickly and at no higher cost. PMID- 8449050 TI - Serial fiberoptic bronchoscopic observations of endobronchial tuberculosis before and early after antituberculosis chemotherapy. AB - STUDY OBJECTIVE: To evaluate the antituberculous treatment responsiveness of endobronchial tuberculosis in the different stages of evolution. DESIGN: A prospective study before and after trial with 9 months of antituberculosis chemotherapy without steroid. PATIENTS AND INTERVENTION: One hundred thirty-six endobronchial lesions in 62 patients were subdivided into four types according to initial fiberoptic bronchoscopic (FOB) findings. Follow-up FOB was performed in 29 patients with 56 endobronchial lesions to detect the changes in the initial endobronchial lesion and bronchostenosis within 3 months after completion of 9 months of chemotherapy. RESULTS: The endobronchial lesions could be classified into four types: exudative (59 lesions, 43.3 percent), ulcerative (13 lesions, 9.7 percent), cicatricial (36 lesions, 26.5 percent), and bronchoglandular (28 lesions, 20.5 percent). In the reassessment of 56 lesions, all 19 exudative and all 9 ulcerative lesions showed complete improvement. Of the cicatricial lesions, most (10 of 12 lesions) showed no change in bronchostenosis, whereas 2 lesions showed improvement. In the bronchoglandular lesions, 6 of 18 lesions showed progressed bronchostenosis. Overall, we observed improved responses in 53.6 percent, progressed bronchostenosis in 10.7 percent, and stationary responses in the remaining 35.7 percent. The progressed lesions were found only in the bronchoglandular lesions. CONCLUSION: In the exudative, ulcerative, and cicatricial lesions, the administration of antituberculous chemotherapy alone resulted in favorable responses in the early posttreatment period. PMID- 8449052 TI - Pulmonary vascular lesions occurring in patients with chronic major vessel thromboembolic pulmonary hypertension. AB - The status of small pulmonary arteries may influence diagnosis, surgical selection and postoperative outcome of patients with chronic major vessel thromboembolic pulmonary hypertension (CTEPH). Therefore, in patients with the established diagnosis of CTEPH, lung tissue was obtained by biopsy (15 patients) or at autopsy (16 patients) to assess the histopathologic composition of small pulmonary arteries. Pathologic examination disclosed the full range of pulmonary hypertensive lesions in the small arteries, including plexogenic lesions. The type and extent of hypertensive lesions did not relate to preoperative hemodynamic values, to patient age, or to symptom duration. The findings indicate that primary pulmonary hypertension cannot be differentiated from potentially correctable CTEPH on the basis of histopathologic findings in small pulmonary arteries. Furthermore, none of the histologic findings preclude a positive hemodynamic and clinical result from pulmonary thromboendarterectomy. However, development of these hypertensive changes may explain the deterioration which these patients experience preoperatively over time. PMID- 8449051 TI - Comparative cost-effectiveness analysis of theophylline and ipratropium bromide in chronic obstructive pulmonary disease. A three-center study. AB - The charts of 311 patients receiving theophylline (T) and 289 patients receiving ipratropium bromide (IB) for COPD were reviewed to determine the total costs and cost-effectiveness of these 2 agents in 3 different health-care settings. A direct cost-accounting method assessed cost, and a Markov decision-analysis model calculated cost-effectiveness. Costs to treat toxic effects were greater for T versus IB. The types and incidences of toxic effects, by drug, were similar among the three centers. Overall costs for T were $121.40 per patient per therapy-month versus $84.56 per patient per therapy-month for IB, as determined by the cost accounting method. The marginal cost was $366 for T over IB when extrapolated over 1 year using the Markov model. The Markov model also predicted that patients receiving IB had a greater number of complication-free therapy-months (measurement of effectiveness) than patients receiving T. We conclude that treatment with IB was less costly and more cost-effective than T. PMID- 8449053 TI - Does cold air affect exercise capacity and dyspnea in stable chronic obstructive pulmonary disease? AB - Cold air may worsen asthmatic bronchoconstriction but can lessen breathlessness in normal individuals. Patients with COPD sometimes report improvement in their dyspnea in cold weather. We examined the effect of breathing cold air on exercise tolerance and the perception of breathlessness in 19 patients with stable COPD (age [+/- SD], 63 +/- 6 years; FEV1, 0.99 +/- 0.28 L) in a randomized open study. Patients exercised on a cycle ergometer breathing either room or cold air (-13 degrees C), breathlessness being assessed by Borg scaling. Peak exercise performance improved when breathing cold air (mean +/- SE), 46 +/- 6 W compared with 37 +/- 7 W (p < 0.05) while end-exercise breathlessness fell from 4.6 +/- 0.4 compared with 4.1 +/- 0.5 (p < 0.05) when breathing cold air. End-exercise ETCO2 was higher breathing cold air (6.1 +/- 0.3 kPa compared with 5.5 +/- 0.3 kPa) (p < 0.005). There was no difference in breathlessness at equivalent levels of ventilation. Cold air reduces breathlessness in COPD, probably by inducing relative hypoventilation. PMID- 8449054 TI - Treatment of community-acquired pneumonia. A multicenter, double-blind, randomized study comparing clarithromycin with erythromycin. Canada-Sweden Clarithromycin-Pneumonia Study Group. AB - The efficacy and safety of orally administered clarithromycin and erythromycin in the treatment of community-acquired pneumonia were assessed in a multicenter, double-blind, randomized study. Two hundred sixty-eight patients were randomized to receive either clarithromycin, 250 mg twice a day, or erythromycin stearate, 500 mg 4 times a day, for 7 to 14 days. Efficacy was evaluable in 173 patients (92 for clarithromycin, 81 for erythromycin). No statistically significant difference in clinical success rate (cure or improvement) was observed between the two groups (clarithromycin, 97 percent; erythromycin, 96 percent). Both groups had identical radiologic response (97 percent with resolution or improvement). Similarly, no statistically significant difference in bacteriologic response toward the target pathogens was observed among evaluable patients (clarithromycin, 23/26; erythromycin, 17/17; p value = 0.287). Clinical response toward Mycoplasma and Chlamydia pneumonia was comparable between the two groups (clarithromycin, 15/16; erythromycin, 10/11). However, patients receiving erythromycin had a twofold higher incidence of adverse events, mostly related to the gastrointestinal system, and were five times more likely to withdraw from therapy because of drug-related adverse events. These results show that clarithromycin is as effective as erythromycin in the outpatient treatment of community-acquired pneumonia. Furthermore, the lower incidence of adverse events associated with clarithromycin indicates that it is more acceptable to patients and, therefore, can enhance compliance. PMID- 8449055 TI - Respiratory health of swine producers. Focus on young workers. AB - In this report, we compare the respiratory health of swine producers, grain farmers, and nonfarming control subjects, separately in all age groups and in young subjects. We examined 249 swine producers (age 37.7 years), 251 grain farmers (age 44.7 years), and 263 nonfarming subjects (age 40.7 years). Swine producers had significantly more symptoms of chronic bronchitis (15.3 percent) than did grain farmers (7.2 percent) or nonfarming men (5.7 percent). After controlling for age, height, and smoking, the functional indices of airflow (FEV1, FEV1/FVC, FEF25-75, Vmax50, and Vmax25) were slightly but significantly lower in swine producers than in grain farmers. In comparison with nonfarming subjects, swine producers also had significantly lower FEV1/FVC, FEF25-75, and Vmax50. Respiratory symptoms were associated with the number of hours of work per day. This indirect index of exposure was also inversely associated with FVC (p < 0.01) and FEV1 (p = 0.06), after adjustment for age, height, smoking, and dust mask usage. A relative excess of respiratory symptoms and lower lung function variables were found in swine producers aged 26 to 35 years. Also in this age group, a multivariate analysis revealed statistically significant effects of daily duration of work on FVC and FEV1. The results confirm that working in swine confinement units is a risk factor for chronic respiratory symptoms and minor lung function changes. An increased risk in young workers may reflect more intense occupational exposure in this subgroup of swine producers. PMID- 8449056 TI - Deaths in bacteremic pneumococcal pneumonia. A comparison of two populations- Huntington, WVa, and Stockholm, Sweden. AB - The case fatality rate in bacteremic pneumococcal pneumonia (Pnb) has been reported to be lower in Sweden than in the United States. We retrospectively compared 231 adult Pnb patients in Stockholm (STO), Sweden, with 107 patients infected with the same serotypes or groups in Huntington, WVa (HWV). The total case fatality rate was 11/231 (5 percent) in STO versus 28/107 (26 percent) in HWV (p < 0.001), being significantly lower in STO for all age groups. Patients from HWV more often had preexisting chronic diseases, while alcoholism was more prevalent in STO. The case fatality rate was similar among alcoholics in STO and HWV, while it was much higher in nonalcoholic patients with chronic diseases in HWV (22/73;30 percent) than in STO (2/88;2 percent) (p < 0.001). No bias was found that could account for more than a small part of the higher case fatality rate in HWV. Thus, underlying chronic diseases in HWV accounted for some of the increased risk of death in this patient group. However, the major part of the difference in death rates between HWV and STO remains unexplained. PMID- 8449057 TI - The relationship between the severity of sleep apnea syndrome and 24-h blood pressure values in patients with obstructive sleep apnea. AB - Automated ambulatory 24-h BP monitoring was made in 38 patients with obstructive sleep apnea syndrome. Stepwise multiple regression analysis revealed that diastolic, systolic, and mean BP values during sleep as well as during wakefulness were significantly related to apnea/hypopnea index and age. Minimal arterial O2 saturation and total sleep time also significantly contributed to diastolic and mean BP values during sleep. Body mass index did not significantly contribute to any of the BP values. These results support a causal relationship between the severity of sleep apnea syndrome and systemic hypertension. PMID- 8449058 TI - Catecholamines and blood pressure in obstructive sleep apnea syndrome. AB - To evaluate the release of catecholamines and their relationship with systemic blood pressure (BP) in normotensive patients with obstructive sleep apnea syndrome (OSAS), diurnal and nocturnal urinary norepinephrine (NE) and epinephrine (E) excretion in 12 normal subjects and in 10 OSAS patients were compared; in addition, nocturnal NE and E excretion were measured in the patients while receiving short-term CPAP. Blood pressure was continuously monitored in the patients during both nights of urine collection. In normal subjects, both NE and E excretion decreased from day to night. In the patients without CPAP, only NE excretion decreased at night, and BP increased from wakefulness to sleep; both NE and E excretion were higher in patients than in normal subjects. With CPAP, which prevented apneas, only E excretion decreased with respect to the previous night, while BP no longer increased during sleep. The extent of nocturnal E decrease with CPAP was not correlated to BP variations. These results suggest that in normotensive OSAS subjects, sympathetic nervous system activity, based on NE excretion, is continuously increased and is not affected by short-term CPAP treatment. Conversely, adrenal activity, based on E excretion, is also increased, but it tends to be normalized by short-term CPAP. No clear relationship could be found between sympatho-adrenal behavior and BP during sleep. PMID- 8449059 TI - Exercise-related potassium and free fatty acid level changes in coronary artery disease. Responses after moderate intensity training. AB - Exercise produces changes in circulating levels of potassium and free fatty acids which may provoke arrhythmias in patients with coronary artery disease. Twenty patients participating in 6 weeks of training were studied; 9 of these patients took part in 4 more weeks of training and a third exercise test. After 6 weeks, potassium levels were higher at submaximal levels of exercise, free fatty acid levels were reduced at rest, and at 5, 15, and at 30 min post-exercise. Norepinephrine levels were reduced at submaximal work loads after 6 weeks and increased at maximal work loads. The extra 4 weeks had no additive effect on these metabolic changes. Participation by coronary artery disease patients in a short-term, moderate intensity, exercise training program increases potassium levels at submaximal work loads and reduces levels of free fatty acids at rest and after exercise. The arrhythmogenic relevance of these findings deserves further consideration. PMID- 8449060 TI - O2 uptake kinetics in response to exercise. A measure of tissue anaerobiosis in heart failure. AB - Oxygen uptake (VO2) reflects the rate of aerobic regeneration of high-energy phosphate compounds (primarily adenosine triphosphate [ATP]). Since lactate increase is thought to result from an inadequate rate of aerobic ATP regeneration, it might be expected that lactate increase would be associated with a delayed attainment of steady state for VO2 in response to constant load exercise. Similarly if mitochondrial ATP regeneration during exercise is inadequately supported by O2 transport mechanisms, adenosine diphosphate (ADP) and purine nucleotide by-products, such as hypoxanthine, should increase. This study investigated the relationship between VO2 kinetics during exercise and accompanying changes in blood lactate and hypoxanthine values in heart failure patients, as a model of compromised O2 transport. Twenty-five patients with chronic heart failure performed cycle ergometry for 6 min at 25 W and at a work rate midway (50 percent delta) between their lactic acidosis threshold (LAT) and peak VO2. Ventilation and gas exchange were measured breath by breath, and venous lactate, hypoxanthine, norepinephrine, and epinephrine were determined at rest and 2 min after each test. The slow component of VO2 kinetics was quantified as the rise in VO2 from the third to the sixth minute of exercise (delta VO2 [6-3]). Ten age- and size-matched normal subjects served as control subjects. delta VO2 (6-3) was correlated with the increase in lactate (r = 0.71, p < 0.001), hypoxanthine (r = 0.61, p < 0.001), and norepinephrine (r = 0.41, p < 0.01) but not epinephrine in response to exercise in the heart failure patients. The delta VO2 (6-3) and delta lactate were both greater in the patients than in the control subjects at similar absolute work rates (54 +/- 20 and 60 W, respectively). However, the slope of the relationship between delta La and delta VO2 (6-3) for the patient and normal groups was indistinguishable. The lactate increase was correlated with hypoxanthine increase (r = 0.66, p < 0.001), but not norepinephrine or epinephrine. In summary, VO2 kinetics in response to exercise reflects delayed attainment of the steady state in heart failure patients, which is correlated with increases in lactate and hypoxanthine, markers of increased anaerobic metabolism. PMID- 8449061 TI - Exercise-induced airflow obstruction in a healthy military population. AB - Clinical asthma is estimated to occur in 4 to 7 percent of the US population, but respiratory symptoms are much more common. The correlation between asthma, tests of bronchial hyperresponsiveness, and symptoms is imprecise and difficult to ascertain. The prevalence of exercise-induced airflow obstruction is not well known in healthy adults. We studied 100 consecutive US Air Force members to determine the prevalence of respiratory symptoms and the incidence of airflow obstruction after standardized free-run exercise. Subjects who developed airflow obstruction with exercise underwent methacholine challenge. We found that 31 percent of our population had respiratory complaints, but only 6 percent had significant airflow obstruction after exercise. Three of six subjects with abnormal results on exercise spirometry had bronchial hyperresponsiveness in response to methacholine. In summary, objective evidence of exercise-induced airflow obstruction was uncommon in our healthy subjects, although nonspecific respiratory complaints were frequent. In our study, methacholine challenge was positive in only half the subjects with abnormal spirometric data after exercise. We conclude that the diagnosis of exercise-induced asthma in healthy individuals is difficult because of the uncertain relationship between symptoms and objective testing and between modes of objective testing. Additionally, the role of free run exercise testing needs further investigation in adults being screened for asthma. PMID- 8449062 TI - Altered exercise gas exchange and cardiac function in patients with mild chronic obstructive pulmonary disease. AB - Patients with advanced COPD have significantly reduced gas exchange and pulmonary function; however, little is known regarding physical work capacity and exercise gas exchange in patients with mild COPD. A total of 39 individuals (20 men and 19 women) without evidence of COPD (controls) and 51 individuals (29 men and 22 women) with mild COPD (FEV1 > or = 60 percent of predicted; and ratio of FEV1 over forced vital capacity of 60 to 70 percent) were tested to determine resting pulmonary function and resting and peak exercise gas exchange in response to progressive maximal cycle ergometer testing. In general, those with mild COPD had similar smoking histories and essentially equivalent resting gas exchange studies as compared to the controls. Measured maximal oxygen consumption was less in both the male (p < 0.003) and the female patients (p < 0.001). This was due, in part, to a lower maximal ventilation in the men with obstruction (p < 0.04), resulting from a significant reduction in tidal volume (p < 0.05). Women presented with similar decreases in maximal ventilation (p < 0.04) and maximal tidal volume (p < 0.01), while no difference in maximal respiratory rate was noted in either group (p > 0.05). Breathing reserve was 32 percent and 53 percent less for the male and female patients with obstruction than for controls. Maximal heart rates were less in the individuals with obstruction, where they reached 93 percent (p < 0.02) and 96 percent (p < 0.003) of the age- and sex-specific maximal heart rates for men and women as compared to 101 percent and 99 percent obtained in the controls. Achieved absolute work loads for men and women (in kilogram.meters per minute) were lower in the groups with obstruction (p < 0.002 and 0.0003) as well. These results demonstrate that work capacity and gas exchange are significantly decreased in individuals with even mild COPD. The reduction in functional work capacity is secondary to a loss of pulmonary function, as well as chronic deconditioning. Increased dyspnea may be responsible for the premature cessation of exercise observed in patients with mild COPD. Thus, early intervention with exercise training may be warranted to counter the deleterious effects of deconditioning and declining pulmonary function in patients with mild COPD. PMID- 8449063 TI - Red cell magnesium concentration in cor pulmonale. Correlation with cardiopulmonary findings. AB - Atomic absorption spectrometry was used for red cell (MgRC) and plasma Mg (MgPL) measurement (mEq/L) in 24 normal individuals (Nls), aged 42.16 +/- 16 years, and 44 carefully selected consecutive patients (pts), aged 60.68 +/- 10 years with cor pulmonale. The results showed the following: (1) normal MgPL (1.69 +/- 0.19) and MgRC (4.22 +/- 0.32) in Nls; (2) decreased MgpL (1.56 +/- 0.23) and MgRC (2.85 +/- 0.54) in pts; (3) decreased FEV1 percent (37.56 +/- 13.1) in pts; (4) increased RVIDd (1.73 +/- 0.31 cm/m2) of the pts by M-mode echo; and (5) coexistence of decreased MgRC (2.55 +/- 0.33) and ECG arrhythmias-RBBB in 17/44 Pts (38.6 percent). We conclude the following; (1) red cell Mg concentration was more significantly decreased (p < 0.001) than plasma Mg concentration (p < 0.01); (2) there was no significant correlation coefficient (r) between red cell and plasma Mg concentration of pts (p > 0.05); (3) there was significant statistical difference between decreased red cell Mg levels in pts with and without ECG arrhythmias-RBBB (p < 0.01); (4) significant r between decreased red cell Mg concentration and aRVIDd (r = -0.43, p < 0.01), beta FEV1 percent (r = 0.47, p < 0.01); and (5) decreased red cell Mg levels of unknown origin have never been reported previously in the literature. Subsequently, could Mg salt intake attenuate pulmonary dysfunction and right ventricular dilatation in pts with chronic cor pulmonale? PMID- 8449064 TI - One negative polysomnogram does not exclude obstructive sleep apnea. AB - Night-to-night variability of apneas on overnight polymnography exists in patients with documented obstructive sleep apnea (OSA). In this study, we evaluated the possibility that this variability may be severe enough to miss the diagnosis of OSA in patients clinically at risk for the disease. We prospectively studied 11 patients who were deemed on clinical grounds to have probable OSA, but had a negative result on overnight polysomnography. Six of the 11 patients were found to have a positive second study with a significant rise in the apnea/hypopnea index (AHI) from 3.1 +/- 1.0 to 19.8 +/- 4.7 (mean +/- SEM, p < 0.01). The cause of the negative first study in these patients is unclear, but it does not seem related to risk factor pattern, sleep architecture, or test interval. The change in AHI was not found to be rapid eye movement (REM) dependent. This study demonstrates that a negative first-night study is insufficient to exclude OSA in patients with one or more clinical markers of the disease. PMID- 8449065 TI - Congenital cystic adenomatoid malformation. AB - Congenital cystic adenomatoid malformation is an uncommon congenital anomaly. We present four additional children with CCAM and review the literature. Two of these children had unusual manifestations of CCAM--one presented with a "cavitary lesion" while the other is suspected of having bilateral disease. PMID- 8449066 TI - Comparison of video thoracoscopic lung biopsy to open lung biopsy in the diagnosis of interstitial lung disease. AB - BACKGROUND: Up to one third of patients with interstitial lung disease will require a lung biopsy for diagnosis. Open lung biopsy is generally accepted as the most reliable method of biopsy and tissue diagnosis. The purpose of this study was to compare the efficacy and safety of video thoracoscopic lung biopsy, a minimally invasive technique, with open lung biopsy in the diagnosis of interstitial lung disease. METHODS: From December 1990 to January 1992, 43 patients were referred for diagnostic lung biopsy. Twenty-two consecutive patients undergoing video thoracoscopic lung biopsy (VTLB) over a 6-month period were retrospectively studied and compared with 21 consecutive patients who had undergone open lung biopsy (OLB) in the preceding 6-month period. RESULTS: VTLB (46 +/- 4 minutes) did not add to operative time when compared with OLB (38 +/- 3 min, p = 0.09). The same number of biopsies per patient were performed (VTLB, 1.9 +/- 0.1; OLB, 2.0 +/- 0.1; p = 0.48), the same amount of tissue was obtained per biopsy (VTLB, 6.69 +/- 0.82 cm3; OLB, 5.78 +/- 0.54 cm3; p = 0.36), and the diagnostic accuracy of each method was comparable (VTLB, 95 percent; OLB, 100 percent). However, patients undergoing VTLB demonstrated a significant reduction in length of pleural drainage (1.36 +/- 0.25 days) and hospital stay (2.57 +/- 0.46 days) relative to patients undergoing OLB (3.20 +/- 0.34 days, 5.71 +/- 0.63 days; p < 0.05). Complications occurred in 2/22 VTLB patients (9 percent, 0 deaths) and 4/21 OLB patients (19 percent, 1 death). CONCLUSIONS: When compared with OLB, VTLB does the following: (1) provides equivalent specimen volume; (2) achieves equal diagnostic accuracy; (3) does not add to operative time or complications; and (4) reduces the time necessary for pleural drainage and length of hospital stay. Our findings suggest that VTLB is an effective and safe alternative to OLB in the diagnosis of interstitial lung disease. PMID- 8449067 TI - A placebo-controlled dose-finding study with bambuterol in elderly patients with asthma. AB - A new long-acting bronchodilator prodrug, bambuterol hydrochloride, was tested in a randomized, crossover, and double-blind study in elderly asthmatic patients (aged 64 to 82 years). They received placebo and 5-mg, 10-mg, and 20-mg tablets once daily for a week at each dose. The plasma concentration of the active metabolite, terbutaline, increased linearly with the dose of drug (p < 0.001). Peak expiratory flow rate increased with dose in the morning (p < 0.001 for 10-mg and 20-mg doses) and afternoon (p < 0.05 for 10 mg; p < 0.001 for 20 mg) and was different from placebo for the 10-mg/d and 20-mg/d regimens. The use of supplemental inhaled beta 2-adrenergic agonist therapy was reduced during the night for the 10-mg (p < 0.05) and 20-mg (p < 0.01) doses in comparison to placebo. No significant effects of treatment on blood pressure and pulse were demonstrated. Tremor and palpitations were mild and related to the dose. These data suggest that treatment once daily with bambuterol hydrochloride in a dose of 10 or 20 mg improves pulmonary function and is well tolerated as bronchodilator therapy in elderly patients with asthma. PMID- 8449069 TI - Effect of body position on gas exchange in patients with unilateral central airway lesions. Down with the good lung? AB - In this study, we evaluated the effect of body position (erect, supine, and two decubitus positions) on gas exchange (alveolar-arterial PO2 difference [AaPO2]) in 35 patients who had various degrees of lung collapse roentgenographically caused by unilateral central airway lesions, with special reference to the difference in AaPO2 between two lateral decubitus positions. The patients were divided into two groups. Group 1 was composed of 23 patients with FEV1/FVC > 70 percent. In group 2, there were 12 patients with FEV1/FVC < 70 percent. Our results showed that the mean AaPO2 of group 1 patients was least in the lateral decubitus position with normal lung down (AaPO2N), followed by those in the supine position (AaPO2S), in the lateral decubitus position with lesioned lung down (AaPO2L), and in the erect position (AaPO2E). There was no significant difference in AaPO2 obtained in four positions. However, a significantly negative correlation was found between AaPO2NL (AaPO2N minus AaPO2L) and patient's FEV1 (p < 0.05). In group 2 patients, the mean AaPO2E was least, followed by AaPO2L, AaPO2N, and AaPO2S. The changes of body position did not significantly affect gas exchange in group 2 patients. Unlike previous reports, the present study showed that AaPO2N was not exclusively less than AaPO2L in our patients. AaPO2N was higher than AaPO2L in 11 of 23 in group 1 and in 5 of 12 in group 2 patients. In summary, our results indicated that positional changes did not significantly affect gas exchange in the patients with lung collapse roentgenographically caused by unilateral central airway lesions and the dogma "Down with the good lung" could not be applied to these patients flawlessly. PMID- 8449068 TI - Duration of effect of loratadine and terfenadine administered once a day for one week on cutaneous and inhaled reactivity to histamine. AB - STUDY OBJECTIVE: The duration of action of several new non-sedative antihistamine preparations as assessed by skin and bronchial reactivity to histamine has still not been well established. The aim of the study was to evaluate the duration of effect of loratadine (10 mg) and terfenadine (120 mg) administered once a day for one week on cutaneous and inhaled reactivity to histamine by comparison with a placebo. SUBJECTS: Twenty-four adult asthmatic subjects were included in a parallel group study that compared the duration of effect of two antihistamines and a placebo on cutaneous and inhaled reactivity to histamine. STUDY DESIGN: Baseline cutaneous and inhaled reactivity (concentration causing a fall of 20 percent in FEV1 [PC20]) to histamine was obtained on three consecutive days. Loratadine (10 mg), terfenadine (120 mg) and a placebo loratadine were administered daily for 1 week to 3 groups of subjects. The PC20 was measured at the end of the medication period, 3 days later, and weekly until PC20 returned to baseline value (upper limit of 2 SD from the mean baseline value). RESULTS: The mean blocking duration on cutaneous reactivity for loratadine was 6.9 days and for terfenadine, 7.2 days. The mean duration of the blocking effect on PC20 histamine was 8.5 days for loratadine and 7.2 days for terfenadine. These figures were significantly longer than for the placebo. CONCLUSION: These data suggest that terfenadine and loratadine have a comparable blocking effect on reactivity to cutaneous and inhaled histamine. A daily dose taken for one week will result in a mean blocking effect of one week. PMID- 8449070 TI - Pleural effusion in patients with systemic cholesterol embolization. AB - We evaluated two patients with systemic cholesterol embolization (SCE) associated with the development of pleural effusions. These two patients had evidence of atherosclerosis and presented with livedo reticularis, renal insufficiency, and gangrenous cutaneous changes as manifestations of their SCE. In both cases, closed pleural biopsies demonstrated acute inflammation of the parietal pleura. Our experience with these individuals and a review of the medical literature suggest that pleural injury from atheromatous embolization may occur. Physicians caring for patients with SCE should be aware of the possible association of pleural reactions with this process. PMID- 8449071 TI - Bronchial reactivity to methacholine in HIV-infected individuals without AIDS. AB - To evaluate bronchial reactivity to methacholine in human immunodeficiency virus (HIV) infection, we submitted 25 HIV-seropositive subjects without full-blown AIDS and 25 HIV-seronegative subjects, all inmates in a drug rehabilitation center for previous intravenous drug abuse, to interview and to bronchial challenge with methacholine. Four (16 percent) HIV-seropositve and three (12 percent) HIV-seronegative subjects noted bronchospastic symptoms. Baseline FEV1 and MEF50 percent were within the normal range in every patient. Bronchial hyperreactivity to methacholine (PD20FEV1 < 1,400 micrograms) was found in two (8 percent) HIV-seropositive and in four (16 percent) HIV-seronegative subjects, with no significant difference in the frequency between the two groups. We conclude that HIV infection without AIDS in intravenous drug users does not appear to be associated with an increased frequency of bronchospastic disorders and to bronchial hyperreactivity to methacholine. PMID- 8449072 TI - Effects of buspirone on anxiety levels and exercise tolerance in patients with chronic airflow obstruction and mild anxiety. AB - The objective of this study was to determine if buspirone would alleviate anxiety and improve exercise tolerance of anxious patients with chronic airflow obstruction (CAO). Eleven male patients with mild to moderate anxiety and CAO completed this study comparing buspirone, 10 to 20 mg given three times a day, with placebo. Patients were evaluated with State Trait Anxiety Inventory, spirometry, 12-min walk, incremental exercise on a cycle ergometer to symptom limitation and measurement of dyspnea with a modified Borg scale at exercise levels and the end of each 2 min on 12-min walk. There were no significant differences in anxiety scores, work load, maximum oxygen consumption per minute, maximum expired volume per minute, PETCO2, PETO2, 12-min walking distance or dyspnea scores after 6 weeks of buspirone or placebo therapy. We conclude that administration of buspirone has no significant effect on anxiety levels, exercise capabilities or PETO2 or PETCO2 in patients with CAO and mild anxiety. PMID- 8449073 TI - Variants of alpha 1-antitrypsin in Puerto Rican children with asthma. AB - A survey of 393 Puerto Rican and 354 non-Hispanic pediatric patients at Beth Israel Hospital, New York, revealed a significantly larger percentage of asthmatic subjects among Puerto Ricans, confirming findings of a study of Puerto Rican adults in New York. Assays of alpha 1-antitrypsin (AAT) concentration and phenotypes in 61 Puerto Rican asthmatic children revealed a significantly larger number with an S or Z variant in AAT phenotype. The AAT concentration was not a significant variable in this relationship, since four of five subjects with intermediate deficient AAT concentrations and a PiM phenotype were among control nonasthmatic Puerto Rican subjects. A family history of asthma was more common among asthmatic than control subjects and was most common for variant AAT phenotypes in either asthmatic or control subjects. We speculate that the S or Z variant of AAT affects the inflammatory response in such a way as to predispose to asthma. PMID- 8449074 TI - Occult cancer in patients with acute pulmonary embolism. A prospective study. AB - We prospectively studied 78 consecutive patients with acute pulmonary embolism (PE) to determine the most appropriate workup study for searching for hidden cancer. After a careful physical examination, the following tests were performed: erythrocyte sedimentation rate (ESR), complete blood cell counts, biochemistry, carcinoembryonic antigen levels, chest radiograph, upper gastrointestinal endoscopy, and abdominal ultrasound. If a malignant lesion was suspected, further appropriate tests were performed. After hospital discharge, periodic follow-up was performed on all patients in our outpatient clinic. A malignant lesion was detected in 9 of 78 patients: in 7 of them, cancer was diagnosed during the hospital admission because of acute PE. All but one of these 7 patients were asymptomatic, except for PE symptoms. In three of them some abnormalities on physical examination led to the diagnosis of cancer; in the remaining three patients the diagnosis was suspected from abnormal results of blood tests. Cancer was detected several months after hospital discharge in two additional patients: an esophageal cancer was diagnosed 5 months later in one of the 23 patients who refused endoscopy; and a colonic carcinoma was detected 21 months after hospital discharge in a patient in whom colonoscopy was not performed at the time of hospital admission. When considered overall, cancer was more commonly found in patients with "idiopathic" PE as compared with patients with known risk factors for PE development (6 of 21 patients vs 3 of 51 patients; p < 0.05). On the other hand, one patient died because of massive recurrent PE after a biopsy sample was obtained because of a prostatic node. Gross hematuria had developed shortly after biopsy, and any attempt to increase heparin doses was followed by recurrent hematuria. According to our experience, any decision about procedures that potentially involve bleeding should be carefully individualized in patients with acute PE. PMID- 8449075 TI - Does the hypoxic ventilatory response predict the oxygen-induced falls in ventilation in COPD? AB - The purpose of this study was to determine whether supplemental oxygen-induced decreases in ventilation (VE) and mouth occlusion pressure (P0.1) in patients with COPD are related to the ventilatory or P0.1 responses to hypoxia (delta VE/delta SaO2, delta P0.1/delta SaO2). We measured these responses in 14 patients with a (mean +/- SD) FEV1 of 0.95 +/- .41 L. The VE and P0.1 were also measured while the patients sequentially breathed either room air or supplemental oxygen (1-2 L/min) for 10 min in a randomized single blind fashion. The mean (+/- SEM) SaO2 increased from 90.8 +/- 0.99 percent to 95.2 +/- 0.46 percent and the VE decreased during oxygen breathing from 12.3 +/- 0.46 to 11.6 +/- 0.47 L/min (p < 0.03). However, the individual changes in VE were not significantly related to the corresponding changes in SaO2 (CHG SaO2), (delta VE/delta SaO2), or (delta VE/SaO2) (CHG SaO2). Similarly, the P0.1 decreased from 2.50 +/- 0.27 to 2.26 +/- 0.20 cm H2O (p < 0.05), but the individual changes in P0.1 were not significantly related to (CHG SaO2), (delta P0.1/delta SaO2), or (delta PO.1/delta SaO2) (CHG SaO2). PMID- 8449076 TI - Preventive therapy for the patient with both universal indication and contraindication for isoniazid. AB - BACKGROUND: The delphi method of decision making was used to address an unusual clinical case in which various aspects of the case required opposing management strategies. METHODS: A panel of 30 pulmonary experts was surveyed repeatedly until a convergence of treatment approaches was reached for a patient who was considered to have both a universal indication for and a universal contraindication against prevention therapy. Participants were asked to evaluate the appropriateness of proposed treatments on a scale from 1 to 9, with 1 being extremely inappropriate, 5 being equivocal, and 9 being extremely appropriate. The delphi survey data responses were compared using measures of central tendency (ie, the mean and median) and measures of variability (ie, the standard deviation and interquartile range). RESULTS: Although no treatment was wholeheartedly supported by the experts, analysis of the three-round delphi survey responses resulted in two possible treatments: rifampin, 600 mg daily, for four months, or no treatment with close observation. Interestingly, the experts working in a non university setting favored the rifampin treatment, and those working in a university setting favored no treatment with close observation. CONCLUSIONS: The delphi method has the potential to be used for clinical decision making. PMID- 8449077 TI - The relationship between alveolar macrophage TNF, IL-1, and PGE2 release, alveolitis, and disease severity in sarcoidosis. AB - A mononuclear cell alveolitis, comprised in part of activated macrophages, is thought to precede granuloma formation and fibrosis in pulmonary sarcoidosis. Tumor necrosis factor-alpha (TNF), interleukin 1-beta (IL-1), and prostaglandin E2 (PGE2) are potent mediators released by activated alveolar macrophages. To determine if alveolar macrophage TNF, IL-1, and PGE2 release was associated with clinically progressive pulmonary sarcoidosis, we obtained alveolar macrophages from bronchoalveolar lavage of 68 patients with biopsy specimen-confirmed sarcoidosis, cultured the macrophages in the presence and absence of lipopolysaccharide (10 mg/L) for 24 h, and measured TNF (enzyme-linked immunosorbent assay), IL-1 (enzyme-linked immunosorbent assay), and PGE2 (radioimmunoassay) release. Alveolar macrophages from most patients with sarcoidosis spontaneously released TNF, IL-1, and PGE2. The amounts of these mediators released (either spontaneously or following lipopolysaccharide stimulation) did not positively correlate with the numbers of any of the cells in bronchoalveolar lavage fluid, the clinical status of disease (stable vs deterioration), steroid usage, or cigarette smoking. The relative release of each of the individual mediators, however, was highly correlated with the release of the other mediators. The studies suggest that these markers of alveolar macrophage activation from a single bronchoalveolar lavage are poor indicators of clinically progressive disease. PMID- 8449078 TI - Empyema of the thorax in adults. Etiology, microbiologic findings, and management. AB - The etiology, microbiologic findings, and management of 82 episodes of empyema treated by our unit over a period of 6 years were analyzed. Average patient age was 54 years. Eighty-two percent had underlying disease such as alcoholism (29 percent), malignancy (23 percent), and diabetes mellitus (20 percent). Sixty (73 percent) had an empyema develop secondary to a bronchopulmonary infection. Other etiologies were as follows: infradiaphragmatic sepsis, five cases; iatrogenic, ten cases; and idiopathic, seven cases. Cultures were positive in 76 cases and negative in the remaining 6 (2 positive Gram stains, 1 positive under bacilloscopy, and 3 were sterile). Anaerobes were isolated from 25 and aerobes from 47 of the positive cultures. A single bacteria was isolated from 43 and multiple organisms (average: 2.63/case) grew on the remaining 33 positive cultures. Length of hospitalization averaged 37 days. Seven patients received antibiotics only, thoracentesis was performed on three, intercostal chest tube drainage was required in 72, and more aggressive surgery was performed on 12 patients (7 with fibrothorax and 5 with pneumonectomy). Streptokinase was instilled into the pleural space of eight patients with good results. Pleural drainage superinfection occurred at a rate of 8.5 percent. Nine patients died; the remaining recovered. Only three deaths came about as a direct result of the empyema. PMID- 8449079 TI - Thrombotic lesions in primary plexogenic arteriopathy. Similar pathogenesis or complication? AB - In 78 patients with primary plexogenic arteriopathy (PPA), numbers of organized and recanalized thrombi were established in histologic slides of lung tissue and expressed per square centimeter of section. Three control groups of ten individuals each were used: normal, plexogenic arteriopathy secondary to ventricular septal defect, and hypoxic pulmonary hypertension. Thrombotic lesions were scarce in normal individuals but numerous in all three groups with pulmonary hypertension. There is also a positive correlation with age. Thrombotic lesions are absent or scarce in children but more common in adults, even in normal control subjects and particularly in pulmonary hypertension by whatever cause. In PPA there is likely to be a relation with the duration of illness but not with the stage of the disease. The complete pattern of plexogenic arteriopathy may develop in the absence of thrombotic lesions, which clearly are not essential for its pathogenesis. Rather than being part specifically of PPA, as sometimes suggested, thrombotic lesions complicate various types of hypertensive pulmonary vascular disease. Apparently the combination of sustained pulmonary hypertension and age, possibly through endothelial injury, may elicit thrombosis and its sequelae, which in turn may aggravate the pulmonary arterial pressure. PMID- 8449080 TI - Incidence and natural history of phrenic neuropathy occurring during open heart surgery. AB - OBJECTIVE: To study the incidence of phrenic neuropathy following coronary artery bypass grafting and determine long-term outcome. DESIGN: Prospective observational. SETTING: Surgical ICU in a university hospital, out-patient follow up. PATIENTS: Ninety-two consecutive patients undergoing open heart surgery. INTERVENTIONS: None. MEASUREMENTS: Chest radiographs (CXR) 48 to 72 h post operatively, ultrasonography of diaphragm, phrenic nerve conduction studies, diaphragmatic electromyogram, each repeated every 1 to 3 months until normal. MAIN RESULTS: Seventy-eight of 92 (78 percent) patients had abnormal radiographs, 42 of 78 (54 percent) with abnormal CXRs had abnormal diaphragm motion, 24 of 42 (57 percent) with abnormal motion had phrenic neuropathy. Patients with normal diaphragm motion improved faster than those without; patients with normal nerve conduction (and abnormal motion) improved faster than those with abnormal nerve conduction. CONCLUSIONS: Phrenic neuropathy is relatively common if sensitive tests are utilized for diagnosis. Nerve conduction studies can predict duration of morbidity. Most patients have low morbidity and recover fully. Abnormal diaphragm motion alone is not diagnostic of phrenic nerve injury. PMID- 8449081 TI - Diffusing capacity decreases after heart transplantation. AB - We evaluated the following spirometric values: forced vital capacity (FVC), first second expiratory volume (FEV1), FEV1/FVC, the lung volumes, total lung capacity (TLC), residual volume (RV), and single breath diffusing capacity for CO in 22 patients, before and after heart transplant. We found abnormal pulmonary function in 21 patients before heart transplantation. Despite postoperative increases in lung volumes in 10 patients, abnormal pulmonary function persisted in 20 patients after heart transplant. Mean values for lung volumes and flow rates did not change but diffusion for CO decreased significantly after heart transplantation. Diffusion failed to correlate with ejection fraction, pulmonary arterial pressure, pulmonary capillary wedge pressure (PCWP), and pulmonary vascular resistance; however, in a subset of patients with improved postoperative lung volumes, preoperative diffusion for CO correlated with preoperative PCWP. We conclude that pulmonary function abnormalities are common among heart transplant recipients. Diffusion abnormalities are not linearly related to indices of cardiac function measured before transplantation and diffusion abnormalities appear to be multifactorial in cause. The posttransplant decrease in diffusion appears to result from the combined effects of decreased postoperative lung volumes in some patients and relief of heart failure induced pulmonary vascular engorgement in others. Improvement in lung volumes and flow rates may occur but cannot be expected after heart transplantation, and diffusion decreases after heart transplantation. The fact that pulmonary function and lung volumes do not improve following heart transplantation implies to underlying lung disease or permanent lung alterations result from chronic heart failure. PMID- 8449082 TI - Bronchogenic carcinoma in young patients at risk for acquired immunodeficiency syndrome. AB - Several case reports have suggested that bronchogenic carcinoma occurs more frequently in young patients who are human immunodeficiency virus (HIV) seropositive. We investigated the incidence of bronchogenic carcinoma and its clinical presentations in young patients at risk for HIV infection. The tumor registry of Bellevue Hospital was reviewed, and 261 cases of bronchogenic carcinoma during the period from 1976 to 1979 (pre-AIDS period) and 232 during the period from 1987 to 1990 (AIDS period) were identified. These cases were stratified into age groups: 45 or younger, 46 to 55, 56 to 65, and 66 years or older. All patients aged 45 years or younger in the AIDS period were subdivided by HIV risk, and clinical characteristics were compared among the subgroups. Results revealed no increased incidence of bronchogenic carcinoma from the pre AIDS period compared with the AIDS period. These results suggest that HIV seropositivity is not a risk factor for bronchogenic carcinoma. PMID- 8449083 TI - Intravascular volume loading reversibly decreases airway cross-sectional area. AB - High-resolution computed tomography was used to directly determine the short-term effects of intravascular volume expansion on airway caliber. The change in airway cross-sectional area caused by intravascular volume expansion (30 ml/kg, Ringer's lactate) was studied in six anesthetized mini-pigs within 5 min. Twenty-five of 27 large airways (diameter, 2.01 to 5.0 mm) demonstrated decreased internal cross sectional area (10.56 +/- 1.26 vs 8.66 +/- 1.03 mm2, p < 0.001). Twenty of 24 small airways (diameter, 0.75 to 2.0 mm) showed decreased internal cross sectional area (1.82 +/- 0.16 vs 1.44 +/- 0.16 mm2, p < 0.001). These changes were rapidly (< 6 min) reversed by intravascular volume reduction. The external airway cross-sectional area did not change. These data suggest rapid, reversible bronchial mucosal vascular engorgement as a cause of increased airway resistance in heart failure. PMID- 8449084 TI - In-hospital prognostic relevance of a reduced ischemic threshold. Studies in 357 consecutive patients with acute coronary syndromes. AB - In 357 patients with unstable coronary syndromes, a reduced pacing ischemic threshold (1-mm ST-segment depression at a heart rate < or = 150 beats per minute) was an independent predictor of main in-hospital events (death, myocardial infarction, or coronary surgery), which occurred in 33 percent (65/200) of the patients with a reduced threshold and in 8 percent (13/157) of those with a normal threshold (p < 0.0001). The incidences of death and infarction in patients with a normal (> 150 beats per minute), modestly reduced (140 to 150 beats per minute), or severely reduced (< or = 130 beats per minute) threshold were progressively higher (1 percent and 4 percent; 3 percent and 12 percent; and 7 percent and 18 percent respectively; p < 0.01). Thus, a reduced coronary reserve is associated with a fourfold increase in in-hospital complications; and when the reserve is severely curtailed, there may be a sevenfold increase in mortality. PMID- 8449085 TI - Demonstration of a relation between urinary digoxin-like immunoreactive substance and cardiac performance. AB - OBJECTIVE: To determine the relation between urinary digoxin-like immunoreactive substance (DLIS) and cardiac performance. DESIGN: Cohort study. SETTING: Echocardiography laboratory of a university-affiliated teaching hospital. SUBJECTS: Thirty-four individuals referred for echocardiographic studies who had never received cardiac glycosides or other substances known to cross-react with a digoxin radioimmunoassay and had no condition that has been associated with increased DLIS. MEASUREMENTS: Cardiac dimensions and indices of cardiac performance derived from echocardiograms and cardiac Doppler flow studies and concentrations of urinary DLIS, creatinine, and electrolytes. RESULTS: Urinary DLIS ranged from < 0.125 ng (digoxin equivalents) per milliliter (below the sensitivity of the assay) to 0.99 ng/ml, averaging 0.22 +/- 0.24 ng/ml. On bivariate analyses, UDLIS was found to correlate significantly with body weight, left ventricular (LV) end-diastolic dimension, LV fractional shortening, mitral transvalvular flow velocity following atrial systole, and urinary calcium. On multivariate analyses, the association between urinary DLIS (alone or adjusted for urinary creatinine) and LV fractional shortening emerged as the paramount independent relation. CONCLUSION: Urinary DLIS can be related to cardiac performance under steady-state conditions. This suggests that DLIS may be a ligand for a cardiac glycoside receptor. PMID- 8449086 TI - Efficacy of 1.4 percent sodium citrate in maintaining arterial catheter patency in patients in a medical ICU. AB - PURPOSE: The primary purpose of this study was to compare the efficacy of 1.4 percent sodium citrate with heparin, 4 U/ml, for maintaining radial artery catheter patency in patients in the medical ICU. PATIENTS AND METHODS: Patients in the medical ICU (n = 40) were randomized to either a 1.4 percent sodium citrate or heparin 4 U/ml arterial line flush solution in a double-blind, parallel fashion. The flush solutions were continuously infused at approximately 3 ml/h over a maximum of 96 h. Catheter survival rates were compared using Kaplan Meier survival curves. The frequency of catheter malfunctions and corrective manipulations were recorded and compared. Coagulation status (APTT, PT) and ionized calcium values were monitored to evaluate the systemic effects of sodium citrate. RESULTS: Ninety-four percent of catheters flushed with sodium citrate were functional at 48 h compared with 88 percent for heparin (p > 0.05). At 96 h, 80 percent vs 88 percent of the catheters were functional in the citrate and heparin groups, respectively (p > 0.05). Frequency of catheter malfunctions did not differ between the two groups. No systemic effects of sodium citrate were observed. CONCLUSION: Arterial catheter flush solutions containing sodium citrate (1.4 percent) are an effective and safe alternative to heparin in patients requiring peripheral arterial catheterization. PMID- 8449087 TI - Response of critically ill patients to treatment aimed at achieving supranormal oxygen delivery and consumption. Relationship to outcome. AB - STUDY OBJECTIVE: To evaluate the response to therapy aimed at achieving supranormal cardiac and oxygen transport variables (cardiac index [CI] > 4.5 L/min/m2, oxygen delivery [DO2] > 600 ml/min/m2, and oxygen consumption [VO2] > 170 ml/min/m2) in a heterogenous group of critically ill patients and to assess its relationship to outcome. DESIGN: Patients were divided retrospectively into two groups. Group 1 (n = 15) achieved supranormal values for CI, DO2 and VO2 simultaneously during the first 24 h. Group 2 (n = 17) failed to achieve these goals simultaneously at any time point. SETTING: General intensive care units in a teaching and a district general hospital. PATIENTS: Thirty-two patients at risk of developing multiple organ failure were studied prospectively. INTERVENTIONS: Patients received volume expansion and then, if necessary, dobutamine (5 to 200 micrograms/kg/min) to increase CI and DO2 until all three goals were achieved simultaneously. RESULTS: In group 2, target VO2 could never be reached despite the fact that 11 (65 percent) patients achieved target CI and DO2 simultaneously. In this group, lactate levels did not fall and 16 patients died. In contrast, in group 1, attainment of all goals was associated with a significant reduction (p < 0.05) in blood lactate levels, and all but one of these patients survived. The persistently raised lactate levels in group 2 were associated with significantly higher venous oxygen saturation (SvO2) and lower oxygen extraction ratio (OER); in these patients, SvO2 rose and OER fell in response to increases in DO2. CONCLUSION: These results suggest that failure to increase VO2 was related predominantly to an inability of the tissues to extract or utilize oxygen rather than a failure to increase DO2. These findings support the hypothesis that in order to survive a critical illness, patients must achieve a high level of VO2. An inability to do so is reflected in persistently elevated blood lactate levels and an extremely poor prognosis. PMID- 8449088 TI - Value of bedside plating of semiquantitative cultures for diagnosis of central venous catheter-related infections in ICU patients. AB - We compared semiquantitative central venous catheter tip cultures plated at the bedside with those cultured in the laboratory, to determine if bedside plating provides a significantly better yield. Paired segments of 197 catheter tips from 92 surgical and medical ICU patients were evaluated prospectively. A total of 31 catheter tip cultures were positive for > or = 15 organisms per agar plate, with 10 of these being simultaneously positive at the bedside and in the laboratory. Cultures were exclusively positive in 18 cases plated immediately at the bedside, whereas laboratory plating resulted in only 3 exclusively positive cases. This discrepancy was statistically significant (p < 0.005). Compared with bedside plating, the sensitivity and specificity of sending catheters to the laboratory were 36 percent and 98 percent, respectively. These results indicate that the practice of sending central venous catheter tips to the laboratory for routine culture should be reconsidered in favor of bedside plating. PMID- 8449089 TI - Mixed venous oxygen saturation in critically ill septic shock patients. The role of defined events. AB - STUDY OBJECTIVE: To investigate the frequency and extent of spontaneous changes ("events") in continuously measured mixed venous oxygen saturation (SvO2) in septic patients and to determine whether attention to individual event-frequency offers additional information for patient management. DESIGN: Nonrandomized prospective study. SETTING: General intensive care unit at a university hospital. PATIENTS: Fifteen patients suffering from septic shock and multiple organ dysfunction syndrome. MEASUREMENTS: For the continuous assessment of SvO2 a fiberoptic pulmonary artery catheter (Baxter Edwards) was inserted in all patients. A certain event was defined as a sudden change in SvO2 of > or = 5 percent lasting for > 10 min. All events were grouped as either moderate (< or = 10 percent changes in SvO2) or severe events (> 10 percent changes). Hemodynamics and inotropic support, oxygenation and ventilatory support, hemoglobin levels and body temperature were determined at the event and compared with the ultimate values registered before the event. RESULTS: We evaluated 377 events during an observation period of 1,575 h. Patients' mean SvO2 levels ranged between 72 +/- 7 and 82 +/- 4. Desaturations below 65 percent (39 out of 377 events) occurred in 11 patients. Overall, 74 percent of all events were moderate and 26 percent were severe. The incidence of events was 5.6 +/- 1.5 during 24 h in survivors (n = 10) and 6.3 +/- 1.6 during 24 h in nonsurvivors (n = 5). While in survivors only 20 percent of all events were severe events, this portion was significantly higher in nonsurvivors (34 percent; p = 0.03). In 67 percent of all events we observed changes in the registered physiologic parameters or therapeutic interventions probably causing the event. The cause of the remaining 33 percent of all events could not be elucidated. CONCLUSIONS: The SvO2 of septic shock patients is mainly normal or even supranormal. However, short-term changes in SvO2 do occur frequently in these patients. Nonsurvivors exhibit a higher frequency as well as a significantly greater severity of events, which may point toward a concealed mismatch of oxygen supply and demand. A high incidence of short-term SvO2 changes in a septic shock patient may be of diagnostic and prognostic significance. Therefore, we recommend the installation of a computerized alarm-function for the automatic detection and indication of frequent events. PMID- 8449090 TI - Noninvasive pressure support ventilation in patients with acute respiratory failure. AB - To further delineate indications for noninvasive pressure support ventilation (NIPSV), we proposed this noninvasive technique as an alternative to endotracheal intubation in 17 consecutive patients with acute respiratory failure from various causes. Eight patients (47 percent) were successfully ventilated with NIPSV, while in 9 (53 percent), NIPSV failed. Gas exchange values before initiating NIPSV were different between the 2 groups: patients successfully ventilated with NIPSV had a higher PaCO2 (57 +/- 15 mm Hg vs 37 +/- 17 mm Hg; p = 0.01), a lower pH (7.33 +/- 0.03 vs 7.45 +/- 0.08; p = 0.02), and a lower alveolo-arterial oxygen pressure difference (P[A-a]O2) (144 +/- 46 mm Hg vs 265 +/- 18 mm Hg; p = 0.01), suggesting that CO2 retention without major hypoxemia is a better indication for NIPSV than severe hypoxemia alone. Acute respiratory failure occurring after extubation seemed to be a good indication for NIPSV, with an 83 percent rate of success. In both groups of patients, gas exchange improved after 1 h on NIPSV, but such values were not improved on the first day in patients who failed with NIPSV. PMID- 8449091 TI - Assessment of therapeutic benefit in asthmatic patients. The International Clinical Respiratory Group. PMID- 8449092 TI - Pulmonary atelectasis and dysphagia in a 69-year-old cachectic man. PMID- 8449093 TI - Dosing efficiency and particle-size characteristics of pressurized metered-dose inhaler aerosols in narrow catheters. AB - An experimental in vitro model was used to determine the effects of intraluminal catheter diameter and length on the delivered dose and particle-size characteristics of salbutamol (albuterol) aerosol delivered by metered dose inhaler (MDI) (Ventolin, 100 micrograms per puff). The dose of aerosolized drug that exited a 16-cm-long tracheal tube with an inner diameter (ID) of 6 mm was compared with that from 4 catheters of differing diameters and lengths that were inserted individually into the tracheal tube. The salbutamol MDI canister was actuated ten times into each delivery system, and the effluent aerosol was trapped onto a filter. The filtrate was dissolved in methanol, and the salbutamol concentration was determined using high-performance liquid chromatography. For the 3 22-cm-long catheters, the delivered dose (mean +/- SD) of salbutamol per actuation for the 22-standard wire gauge (SWG) catheter was 97.5 +/- 3.9 micrograms, which was similar to that for the 19-SWG catheter (102.3 +/- 2.5 micrograms) but was significantly less than that for the 14-SWG catheter (108.2 +/- 4.2 micrograms) (p < 0.05). These delivered doses exceeded those of the 6.0 mm-ID tracheal tube alone (2.33 +/- 0.76 micrograms) and the 13-cm-long 19-SWG catheter (2.17 +/- 0.29 micrograms) (p < 0.001). In a second experiment using a cascade impactor, the distribution of aerosol particle diameters that exited the 6-mm-ID tracheal tube was compared with that exiting a 13-cm-long 19-SWG catheter that extended halfway down the tracheal tube and with that exiting a 22-cm-long 19-SWG catheter inserted into the distal end of the 6-mm-ID tracheal tube. The mass median aerodynamic diameter (mean +/- SD) of the salbutamol aerosols delivered through both the 6.0-mm-ID tracheal tube (1.1 +/- 0.1 microns) and that of the 13-cm-long 19-SWG catheter (1.2 +/- 0.2 microns) were significantly less than that delivered through the 22-cm-long 19-SWG catheter (2.0 +/- 0.1 microns) (p < 0.05). The authors conclude that delivery of respirable aerosol can occur through narrow catheters that function as extended nozzles for MDIs. Optimal dosing will be obtained when the catheter extends the full length of the tracheal tube. PMID- 8449094 TI - Altered mental status, hypoxemia, and a rash in a 32-year-old man. PMID- 8449095 TI - Anatomic correlates of reversible restrictive lung disease. AB - A 19-year-old woman presented with lifelong asthma. Pulmonary function studies revealed a mixed restrictive-obstructive pattern, with significantly decreased elastic recoil as demonstrated by a pressure-volume study. Upon administration of inhaled bronchodilator, however, the patient's lung volume and compliance returned to normal, illustrating the rare phenomenon of reversible restrictive lung disease. Open lung biopsy revealed respiratory bronchiolitis, confirming the suspected involvement of small airways. Mechanisms of reversible restriction, specifically alveolar duct constriction, are discussed. The authors speculate on the observed relation between anatomic and physiologic abnormalities. PMID- 8449096 TI - Immunologic therapy for ARDS, septic shock, and multiple-organ failure. AB - Advances in cytokine biology and molecular biology have led to the development of novel immunologic approaches to the treatment of septic shock, ARDS, and MOF. These advances are necessary since improvements in supportive care clearly fall short of the hoped-for reductions in mortality associated with these disorders. As noted in this review, these new therapies are directed at three distinct levels of the inflammatory cascade: (1) the inciting event or insult (eg, endotoxin); (2) the mediators (eg, TNF, IL-1); and (3) the effector cells (eg, neutrophils). The current status of these treatments has been reviewed; and while each individual therapy has shown potential, it is likely that combinations of these agents may be necessary to substantially impact on survival. That is, due to the complexity and redundancy of the inflammatory network, it is doubtful that a "magic bullet" will be found. However, it is also clear that advances in our understanding of the pathogenesis of ARDS, septic shock, and MOF at the molecular level have provided clinicians with powerful weapons with which to do battle. It remains to be seen which ones will work the best. PMID- 8449097 TI - The diagnosis of a pulmonary artery thrombus by transesophageal echocardiography. AB - We describe a patient with an acute inferior wall myocardial infarction who underwent percutaneous coronary angioplasty. He subsequently had a cardiac arrest and developed progressive severe hypoxia. Although findings from pulmonary angiography were nondiagnostic, transesophageal echocardiography demonstrated a nonocclusive, right pulmonary artery thrombus. Therapy was changed, and the patient recovered. Transesophageal echocardiography was also used to monitor anticoagulation therapy. PMID- 8449098 TI - Multiple myeloma complicated by restrictive cardiomyopathy and cardiac tamponade. AB - Restrictive cardiomyopathy from amyloid deposition within the myocardium is a well-described complication of multiple myeloma; however, myelomatous involvement of pericardium with subsequent cardiac tamponade has rarely been described. Optimal treatment for malignant involvement of the pericardium by myeloma cells has yet to be established. The following description is of a patient with myocardial and pericardial manifestations of multiple myeloma. Treatment of the malignant pericardial effusion was implemented with intrapericardial administration of bleomycin. This therapy resulted in no recurrence of pericardial effusion at nine days follow-up. Despite the absence of detectable recurrent effusion, the patient died suddenly from causes felt unrelated to pericardial disease. PMID- 8449099 TI - High-altitude pulmonary edema with pulmonary thromboembolism. AB - High-altitude pulmonary edema (HAPE) is a form of noncardiogenic pulmonary edema. The pathophysiology of HAPE remains unclear. A case of HAPE was associated with pulmonary thromboembolism of a left upper pulmonary artery. Pulmonary thromboembolism was an important factor in development of HAPE in this case. PMID- 8449100 TI - Tension fecal pneumothorax in a postpartum patient. AB - A 20-year-old woman developed severe shortness of breath 4 h after a cesarean section. Chest roentgenogram showed a pleural effusion and tension pneumothorax; insertion of a chest tube drained liquid stool. At surgery she was found to have a left diaphragmatic defect with herniation, strangulation, and perforation of the transverse colon into the pleural cavity. PMID- 8449101 TI - Use of imipenem in the treatment of pulmonary nocardiosis. AB - A case of pulmonary nocardiosis with empyema in a 55-year-old man with macroglobulinemic lymphoma is presented. Treatment with imipenem followed by oral trimethoprim-sulfamethoxazole (TMP-SMX) resolved his symptoms and cleared the roentgenographic abnormalities. This case illustrates the clinical potential of imipenem against Nocardia. PMID- 8449102 TI - Inverse ratio ventilation in ARDS. Improved oxygenation without autoPEEP. AB - Inverse ratio ventilation and related ventilatory modes (eg, pressure release ventilation) have been applied to patients with the adult respiratory distress syndrome (ARDS) with apparent beneficial effects on arterial oxyhemoglobin saturation. While several mechanisms of improved gas exchange have been postulated, many intensive care physicians believe that the development of occult PEEP (autoPEEP; intrinsic PEEP) leads to the observed rise in oxygen saturation. We report here our findings in a patient whose improved oxygenation on inverse ratio ventilation could not be attributed to autoPEEP. PMID- 8449103 TI - Eosinophilic pleuritis due to propylthiouracil. AB - We report a patient who developed eosinophilic pleuritis due to propylthiouracil. Although immunologic side effects associated with thionamides previously have been described, this is the first reported case of an isolated eosinophilic pleural reaction. PMID- 8449104 TI - Goodpasture's syndrome. Unusual presentation after exposure to hard metal dust. AB - An unusual case of Goodpasture's syndrome in a 26-year-old man with occupational exposure to hard metal dust is described. The patient developed a life threatening interstitial lung disease that was followed by a rapidly progressive glomerulonephritis two months later. To our knowledge, association of Goodpasture's syndrome and hard metal exposure has not been reported previously. PMID- 8449105 TI - Liver cirrhosis with severe hypoxemia and paradoxic pulmonary vascular response to graded inspiratory oxygen tension. AB - We present the findings in a patient with liver cirrhosis who showed oppositional pulmonary vascular responses to various alveolar oxygen tensions. In this case the pulmonary artery constricted on exposure to hyperoxia and then gradually dilated during progressive hypoxic inhalation. Such a paradoxic response must result in severe arterial hypoxemia because of severe V/Q mismatching. PMID- 8449106 TI - Invasive pulmonary aspergillosis presenting as massive hemoptysis in a nonimmunocompromised host. AB - An 83-year-old nonimmunocompromised man presented with hemoptysis that progressed to respiratory failure and death. Bronchoscopic cultures grew Aspergillus fumigatus antemortem and an autopsy confirmed multiple abscesses with Aspergillus confined to the lung. PMID- 8449107 TI - Thymic abscess with bacteremia and manubriosternal pyarthrosis in a geriatric patient. AB - We describe a geriatric patient with acute substernal chest pain thought to be due to coronary heart disease, who was subsequently found to have Staphylococcus aureus bacteremia associated with infection of the thymus and manubriosternal joint. To our knowledge, this is the first report of (1) a thymic abscess in a geriatric patient, (2) a thymic abscess associated with bacteremia, (3) extra articular extension of manubriosternal pyarthrosis, and (4) manubriosternal pyarthrosis in the geriatric age group. PMID- 8449108 TI - Iatrogenic aspiration of components of respiratory care equipment. AB - Two cases of airway foreign bodies involving the aspiration of component parts of commonly used respiratory therapy equipment are described. The first case demonstrated the accidental introduction of a washer from a closed catheter suction system into the airway of a patient. The second case involved the accidental introduction of a part of an intubating stylet into the lung. Improper use of this equipment can result in airway foreign bodies and potential respiratory compromise. PMID- 8449109 TI - Giant endocardial blood cyst in left ventricle resected by transaortic valve approach. AB - A 57-year-old man had a histologically proven giant blood cyst in the left ventricle. An encapsulated mobile cystic tumor (3 x 3 x 4 cm), which was attached to the anterolateral papillary muscle by a stalk, was successfully resected by a transaortic valve approach for preserving cardiac function. PMID- 8449111 TI - Aortic stenosis associated with Scheie's syndrome. Report of successful valve replacement. AB - A 62-year-old man who had aortic stenosis associated with Scheie's syndrome (mucopolysaccharidosis [MPS], type I-S) successfully underwent aortic valve replacement. The composition of acidic glycosaminoglycans (acid mucopolysaccharides) of the excised aortic valve analyzed by high-performance liquid chromatography (HPLC) supported the diagnosis of Scheie's syndrome. This article reviews the literature on aortic stenosis in MPS, a rare inherited metabolic disorder, and discusses biochemical features and surgical repair. PMID- 8449110 TI - Respiratory failure due to pulmonary lymphangitis carcinomatosis. AB - A man with primary lung cancer developed respiratory failure due to lymphangitis carcinomatosis that was diagnosed by transbronchial lung biopsy specimen. After combination chemotherapy with high-dose etoposide and cisplatin (CDDP), he was able to cease oxygen therapy and showed improvement of his lymphangitis carcinomatosis. He received a total dose of 13,400 mg/m2 of etoposide. This case suggested that respiratory failure due to lymphangitis carcinomatosis can be a treatable condition. PMID- 8449112 TI - Synchronous carcinoma and soft-tissue sarcoma. The importance of searching for incidental radiation exposure. AB - A 68-year-old woman was found to have synchronous soft-tissue sarcoma of the anterior chest wall and adenocarcinoma of the breast. During her initial interview, she denied prior radiation therapy. On further questioning, it was learned that the patient had been treated for tuberculosis, as a young woman, by the induction of a pneumothorax that was monitored by repeated chest fluoroscopies. Biologically important doses of ionizing radiation can be given as an incidental part of a variety of medical treatments. The importance of searching for atypical radiation exposures, particularly in patients with unusual tumor presentations, is stressed. PMID- 8449113 TI - Noncardiogenic pulmonary edema associated with accidental hypothermia. AB - The pulmonary system may be significantly affected by hypothermia. The association between NCPE and hypothermia is controversial. A 59-year-old man with mild hypothermia presented with NCPE after passive external rewarming following accidental immersion in water. The patient's course was uneventful after 48 h, allowing immediate withdrawal of assisted ventilation and supplemental oxygen. PMID- 8449114 TI - High-altitude pulmonary edema in partial anomalous pulmonary venous connection of drainage with intact atrial septum. PMID- 8449115 TI - Massive hemothorax associated with intrathoracic extramedullary hematopoiesis involving the pleura. AB - Intrathoracic extramedullary hematopoiesis rarely involves the pleura and is usually asymptomatic. We report a 73-year-old woman with myelofibrosis who had pleural involvement with extramedullary hematopoietic tissue that produced a massive hemothorax. Before the diagnosis of extramedullary hematopoietic tissue was established, sclerosis with tetracycline was attempted, which accelerated pleural bleeding and required surgical evacuation. The bleeding was ultimately controlled by low-dose radiation therapy. PMID- 8449116 TI - Shark oil pneumonia. An overlooked entity. AB - Nonprescription drugs are often believed to be innocuous. We present a case of lipoid pneumonia from ingestion of squalene, a derivative of shark liver oil, a popular over-the-counter Asian folk remedy. PMID- 8449117 TI - A mechanical model of auto-PEEP. PMID- 8449118 TI - Closure of a tracheoesophageal fistula by bronchoscopic application of tissue glue. PMID- 8449119 TI - Persistent bronchopleural fistulae in an AIDS patient with Pneumocystis carinii pneumonia. Successful treatment with chemical pleurodesis. PMID- 8449120 TI - An unusual case of severe anaphylaxis due to ipratropium bromide inhalation. PMID- 8449121 TI - Pregnancy complicated by cardiac valvular disease and hypertension. PMID- 8449122 TI - Exposure of health-care workers to aerosolized pentamidine. PMID- 8449123 TI - Tetracycline pleurodesis. PMID- 8449124 TI - Joseph M. Mathews oration. Has the cream risen? Historic review of the development of colorectal surgery in North America. PMID- 8449125 TI - Antioxidant vitamins or lactulose for the prevention of the recurrence of colorectal adenomas. Colorectal Cancer Study Group of the University of Modena and the Health Care District 16. AB - Colonic adenomas represent the natural precursor lesions of most colorectal cancers. The treatment of choice is endoscopic polypectomy. However, after endoscopic removal, polyps recur in a large fraction of cases. Thus, we evaluated the effect of antioxidant vitamins or lactulose on the recurrence rate of adenomatous polyps. After polypectomy, 255 individuals were randomized into three groups. Group 1 was given vitamin A (30,000 IU/day), vitamin C (1 g/day), and vitamin E (70 mg/day); Group 2 was given lactulose (20 g/day); Group 3 received no treatment. Forty-six subjects had to be excluded because the histologic diagnosis was not consistent with adenoma. The remaining 209 individuals were included in the analysis according to the "intention to treat" criterion, though 34 did not adhere to the scheduled treatment or were lost during the follow-up. Subjects were followed at regular intervals for an average of 18 months. Polyps recurring before one year from index colonoscopy were considered missed by the endoscopist. In the 209 evaluable subjects, the percentages of recurrence of adenomas were 5.7 percent, 14.7 percent, and 35.9 percent in the vitamins, lactulose, and untreated groups, respectively. The fraction of subjects remaining free of adenomas, estimated by Kaplan-Meier survival curves, was significantly different among the three groups (log-rank chi-squared = 17.138; P < 0.001). Using Cox's regression analysis, treatment was the only variable that significantly contributed to the model (regression coefficient = 0.905; P < 0.001). In conclusion, either antioxidant vitamins or, to a lesser extent, lactulose lower the recurrence rate of adenomas of the large bowel and can be proposed as chemopreventive agents, at least in high-risk individuals. PMID- 8449126 TI - Fecal short-chain fatty acid concentrations and effect on ileal pouch function. AB - Random stool samples were obtained from 14 ileal pouch-anal anastomosis (IPAA) patients 43 +/- 5 (mean +/- SEM) months after surgery, and the concentrations of individual short-chain fatty acids (SCFAs) were determined by gas liquid chromatography. Stool frequency was determined from a diary recorded for 15 days prior to stool sampling. The frequency, amplitude, and duration of phasic contractions (PCs) within the pouch following infusion of a physiologic concentration of SCFAs and normal saline randomly into the pouch of six IPAA patients were determined manometrically. The mean total SCFA concentration after IPAA did not differ significantly from normal stools (83 +/- 20 mM after IPAA vs. 97 +/- 10 mM for controls; P > 0.05). In the IPAA patients, regression analysis demonstrated an inverse relationship between stools per day and total SCFA concentration (r = 0.73; P < 0.001). Moreover, no change in frequency (3.0 +/- 0.9 vs. 3.2 +/- 0.8 PCs/30 minutes), amplitude (26 +/- 5 vs. 25 +/- 4 mmHg), or duration (23 +/- 3 vs. 26 +/- 2 seconds) of PCs was found after SCFA infusion compared with saline control (P > 0.1). These findings demonstrate that SCFAs are present in ileal pouch effluent and that stool frequency may be related to fecal SCFA concentration. Also, the normal contractile response of the terminal ileum to SCFAs does not occur in the ileal pouch. PMID- 8449127 TI - Is aggressive management of perianal ulcers in homosexual HIV-seropositive men justified? AB - A study was undertaken to assess the etiology, optimal diagnostic method, and incidence of healing of perianal ulcers in HIV-seropositive men. Between March 1990 and December 1991, 26 HIV-seropositive homosexual or bisexual males were referred with perianal ulcerations. According to CDC criteria, three (12 percent) were Class II, six (23 percent) were Class III, and 17 (65 percent) were Class IV. Eighteen patients had one ulcer, five had two ulcers, and two had three ulcers. In one patient the ulcer was circumanal. Patients with superficial erosions were not included. Biopsies were obtained in 23 patients for routine microscopy, HIV, cytomegalovirus, herpes simplex virus, and acid-fast bacilli. Biopsy revealed an immunoblastic lymphoma in one patient. A comparison of microscopy and culture results revealed culture to be more helpful in determining the etiology of these ulcers. Medical treatment included reverse transcriptase inhibitors (zidovudine, dideoxyinosine, and dideoxycytosine), oral and topical Zovirax (Burroughs Wellcome, Research Triangle Park, NC), ganciclovir, and oral broad-spectrum antibiotics. Surgical treatment included lateral internal sphincterotomy in three patients and seton placement in one patient. Follow-up for at least four weeks was obtained in 22 patients. Overall, healing occurred in 15 patients (68 percent): three (20 percent) were Class II, four (27 percent) were Class III, and eight (53 percent) were Class IV. Healing occurred in all four patients who underwent surgical treatment. In conclusion, aggressive diagnostic maneuvers allow the use of both medical and conservative surgical measures to successfully treat the majority of perianal ulcers in this patient population. PMID- 8449128 TI - Feasibility of stoma continence, using electrically stimulated rectus abdominis muscle in pigs. AB - To develop surgical techniques to obtain stoma continence with a muscular sphincter, the anatomy (especially innervation and vascularization patterns) of the human abdominal wall muscles was studied in three cadaver dissections. It was found that transposed rectus abdominis muscle might be positioned as a new sphincter (sphincteroplasty). Next, the feasibility was assessed in six pigs, and the rectus muscle was positioned as a sphincter around a Thiry Vella loop. The use of three different surgical procedures has been assessed: 1) a muscular ring of the proximal rectus was constructed and partly denervated the muscle; 2) the distal end of the Thiry Vella loop was pulled through the middle of the rectus muscle, thereby also introducing partial muscle denervation; and 3) a sling was constructed using the distal muscle part. In four of these six pigs, identical procedures were performed also at the left side. These new sphincters were electrically stimulated (with implanted stimulation devices) to study the feasibility of prolonged sphincter contraction independent of will. Stimulation with a frequency of 25 Hz was used at the right and 2 Hz was used at the left sphincters. It was found that electrical stimulation with a frequency of 25 Hz as well as 2 Hz increased the percentage of Type I (relatively fatigue-resistant) muscle fibers significantly from 42 to 65 percent (n = 6) in the right and from 50 to 67 percent (n = 4) in the left rectus muscle into innervated muscle areas of the sphincters. This increase is considered essential for sustained sphincter function. Stoma continence was not achieved because constructing muscular rings (as a sphincter) caused partial atrophy. Construction of a sling using the distal part of the rectus did not cause substantial atrophy, but continence was not achieved because the dorsal side of the Thiry Vella loop was not completely covered with muscle fibers. PMID- 8449129 TI - Cancer control problems in the Lynch syndromes. AB - The Lynch syndromes account for about 4 to 6 percent of the total colorectal cancer (CRC) burden. Despite more than two decades of documentation in the literature, many physicians fail to recognize the clinical features of these syndromes. The lack of premonitory physical stigmata, coupled with the absence of a biomarker of cancer susceptibility, mandates full reliance on a well orchestrated family history for diagnosis. These deficiencies impede cancer control. Even if the diagnosis is made, proper surveillance and management measures that are responsive to the Lynch syndromes' natural history may fail to be implemented. We describe CRC occurrences in patients from four extended Lynch syndrome kindreds. Failures in cancer control were attributable to poor patient compliance and/or to limited physician knowledge about the natural history and surveillance recommendations for the Lynch syndromes. Physicians need to more effectively educate their high-risk patients about the significance of genetic risk, the natural history of CRC, and the appropriate surveillance strategies in the Lynch syndromes. PMID- 8449130 TI - Impact of computed tomography vs. intrarectal ultrasound on the diagnosis, resectability, and prognosis of locally recurrent rectal cancer. AB - The use of modern techniques of imaging in the postoperative follow-up is reported to allow an earlier diagnosis of local recurrence in patients operated on with anterior resection for rectal cancer and, consequently, to allow a higher percentage of local recurrence resection to be performed. Although intrarectal ultrasound (IU) has proved highly reliable in preoperative staging, its value in relapse detection has been investigated only in retrospective studies and rarely compared with that of computed tomography (CT). The present prospective study aims at evaluating the role of IU vs. CT in the diagnosis of local recurrence and at verifying whether an earlier diagnosis and a higher resectability rate of recurrence result in an acceptable long-term survival. Thirty-seven patients who had undergone low and ultralow anterior resection for rectal cancer (anastomosis within 10 cm of the anal verge) were investigated prospectively. All the patients have been followed up by IU and CT at predetermined intervals. Six local recurrences were detected. CT correctly identified all the local recurrences (sensitivity = 100 percent, specificity = 93 percent, and accuracy = 94.5 percent); IU correctly identified only four of six local recurrences (sensitivity = 66.6 percent, specificity = 93 percent, and accuracy = 89 percent). Four patients with local recurrence underwent surgical treatment (resectability rate = 66.6 percent). Abdominoperineal resection in three patients and Hartmann's procedure in one patient were performed. In the other two patients, extensive metastatic liver involvements contraindicated surgery. All the resected patients were alive after one year; two of them are disease free, and the other two experienced recurrent disease. In conclusion, CT seems to have a higher sensitivity and accuracy in relapse detection. The increase in the local recurrence resectability rate does not result in a significant improvement in long-term survival. However, the good quality of life justifies the high cost of an intensive follow-up and a more aggressive surgical approach. PMID- 8449131 TI - Functional changes associated with short and long lateral ileal reservoirs in a canine model. AB - Colectomy and endorectal ileal pull-through with ileal reservoir (PTR) have become a standard operative procedure for severe ulcerative colitis and familial polyposis coli. Satisfactory results have been reported with a number of different reservoir designs; however, the optimal reservoir size and configuration remain controversial. Two groups of five dogs each, undergoing colectomy and PTR with construction of either 5-cm-long or 18-cm-long lateral ileal reservoirs, were studied to compare defecatory patterns, intestinal transit, and reservoir emptying. Three months postoperatively, dogs with long ileal reservoirs demonstrated a higher stool frequency and made more unsuccessful attempts at defecation. Evacuation of viscous polyethylene glycol solution from the long reservoirs was prolonged during the first hour compared with short reservoirs. Two of the five long reservoirs showed mucosal ulcerations on postmortem examination, whereas none were present in any of the short pouches. Increases in stool water content and subsequent reduction of urine volumes as well as a prolongation in oroanal transit times occurred to a similar degree in both groups. It is concluded that short lateral isoperistaltic reservoirs empty more effectively than do long reservoirs. PMID- 8449132 TI - Do hot baths promote anal sphincter relaxation? AB - Hot perineal baths have been prescribed for the treatment of painful anorectal conditions such as anal fissures and perianal hematomas or for the postoperative care of hemorrhoidectomy. Despite this widely accepted benefit, no studies have been performed to determine whether there is a rational explanation for this procedure. Anorectal manometry was performed in 40 control subjects with no anorectal complaints before and after a hot perineal bath. No significant difference was found between anal pressures at rest or during voluntary contraction before and after the bath. We conclude from this study that no relaxation of anal sphincters can be obtained by hot perineal baths in normal subjects. PMID- 8449133 TI - Rectal endosonography in the evaluation of stenotic rectal tumors. AB - Preoperative evaluation of stenotic rectal tumors is important since they often involve adjacent organs and thus may require additional therapy. Previous reports on endosonographic staging have excluded stenotic tumors because they could not be fully visualized with the available equipment. In this study, we have evaluated the role of endosonography in staging stenotic rectal tumors, with special attention to the use of forward-looking endoprobes. Preoperative staging was performed in 28 patients with stenotic rectal tumors. Tumor extension was evaluated according to the TNM classification, and the results were compared with surgical and histopathologic findings. Endosonography accurately assessed tumor extension in two T2 tumors, 14 T3 tumors, and seven T4 tumors. Three T2 tumors were overstaged, and two T4 tumors were staged as T3. The accuracy was 82 percent. Twenty-two tumors were subject to histopathologic evaluation of lymph nodes. Lymph nodes larger than 1 cm had been seen by endosonography in eight patients, five of whom had nodal metastases. Lymph nodes smaller than 1 cm or no lymph nodes were found in 14 patients, four of whom had nodal metastases. In conclusion, full sonographic visualization of stenotic rectal tumors and thus evaluation of tumor extension can be achieved by using forward-looking endoprobes. PMID- 8449134 TI - Does methodic long-term follow-up affect survival after curative resection of colorectal carcinoma? AB - Records of 487 patients in long-term follow-up after Ro resection of colorectal carcinomas between January 1, 1980 and December 31, 1989 were analyzed. Every patient underwent regular examinations according to a defined schedule after curative resection of colorectal carcinoma. The date of evaluation was June 31, 1991. During a median observation time of 48 months (range, 15-132 months), tumor recurrence was observed in 149 patients (30.6 percent), with 56.4 percent of these suffering from tumor-associated symptoms. As the primary manifestation of tumor recurrence, only distant metastases (DM) were found in 76 patients (51 percent), only local recurrence (LR) in 46 patients (30.9 percent), and both DM and LR in 27 patients (18.1 percent). Patients with rectal carcinoma developed LR more frequently (P < 0.05) (19.5 percent) than patients with colon carcinoma (11.8 percent). The probability of developing distant metastases was not different (P < 0.05) for colon or rectal carcinoma but depended on primary tumor stage (P < 0.05). Only 36 patients (24.2 percent) with recurrence could undergo further curative resection. Fifty patients (33.5 percent) were given palliative therapy, and 63 patients (42.3 percent) were given no oncologic treatment. Only 9 of the 36 patients (6 percent of all recurrence patients) undergoing Ro resection were free of tumor for more than two years. In no case was a third Ro resection possible. The survival time of these patients was increased significantly after Ro resection of tumor recurrence (P = 0.03). Our study suggests that only a very few patients may live longer as a result of regular follow-up programs after curative resection for colorectal carcinoma. PMID- 8449135 TI - Complications of rubber band ligation of symptomatic internal hemorrhoids. AB - In a prospective study, 512 patients undergoing hemorrhoidal band ligation over a seven-year period were followed up to focus on complications. Thirteen patients (2.5 percent) were hospitalized: six with delayed massive rectal bleeding, three with urinary retention, pain, and fever (one developed perianal abscess), and three others with severe pain due to prolapsed thrombotic hemorrhoids (one developed difficulty in urination). One patient developed perianal abscess and perianal fistula two months after ligation. Twenty-four patients (4.6 percent) suffered from minor complications: 11 patients had painful thrombosed hemorrhoids; five experienced slippage of bands; three had mild bleeding; two developed band-related mucosal ulcer; one experienced each time, after two subsequent ligations, priapism lasting several hours; and difficulty in urination and tender induration above the dentate line occurred in two other patients. Rubber band ligation is, in effect, a miniature hemorrhoidectomy and has been considered, until recent reports of fatalities associated with this procedure, as an effective, safe, and efficient method of treating symptomatic second-degree and third-degree hemorrhoids. We conclude that the ability to handle complications that occur secondary to the rubber band ligation and, thereby, prevent sepsis and the low rate of major complications in our study justify reliance on this method of treating symptomatic hemorrhoids. PMID- 8449136 TI - Colonic explosion during diathermy colotomy. Report of a case. AB - Colonic gas explosion, although rare, is one of the most frightening, sometimes fatal iatrogenic complications in endoscopic surgery, but it is much less frequent during laparotomic surgery. Here we describe a case of colonic explosion during colonic diathermy in a patient with rectal cancer. PMID- 8449137 TI - Spinal epidural abscess complicating an ileal J-pouch-anal anastomosis. Report of a case. AB - A 42-year-old man developed recurrent epidural abscesses from an enteroepidural fistula arising from a J pouch. Lower-extremity neurologic deficit in patients with an ileal pouch-anal anastomosis should alert the physician to this rare complication. PMID- 8449138 TI - Use of Toradol in anorectal surgery. AB - Toradol (ketorolac tromethamine; Syntex Labs, Palo Alto, CA) is a nonsteroidal anti-inflammatory drug introduced for intramuscular injection to control postoperative pain. Its action is peripheral. Therefore, it seemed appropriate to inject it directly into the anal sphincter muscles when these are exposed during anorectal procedures. A total of 60 mg (2 cc) are used, divided among the quadrants resected. Four hours postoperatively, 30 mg are given intramuscularly, and the patient is discharged. Any patient who required medication stronger than Darvocet-N-100 (propoxyphene napsylate and acetaminophen; Eli Lilly and Co., Indianapolis, IN) for pain was considered a failure. Seventeen of 100 patients (17 percent) failed to have their pain controlled. Unexpectedly, only two patients (2 percent) needed catheterization for urinary retention. The usual incidence is 20 to 30 percent. To date we have seen none of the complications associated with the use of anti-inflammatory drugs. PMID- 8449139 TI - A more functional loop ileostomy rod. AB - The use of a flat Jackson-Pratt drain for a loop ileostomy rod is described. It elevates the loop, prevents its retraction into the abdomen, and can be cut to precisely the size of the stoma, thereby alleviating the problem of skin excoriation from a poorly fitting appliance. PMID- 8449140 TI - Method for re-establishing patency of a completely closed colorectal anastomosis. PMID- 8449141 TI - Clinical assessment of biomedical technology. AB - The rapid expansion of new, unproven, and often expensive biomedical technology requires controlled clinical assessment before widespread diffusion into clinical practice. The accuracy, reliability, and validity all need to be assessed in an unbiased manner to determine whether implementation is of benefit to the clinician and patient. This article briefly describes the methodology available to determine whether new technologies such as diagnostic imaging techniques may be of benefit in clinical practice. PMID- 8449142 TI - Tiny carcinoids may be malignant. PMID- 8449143 TI - Rectovaginal fistulas and the double-stapling technique. PMID- 8449144 TI - Quantitative structure-activity relationships of cytochrome P-450. PMID- 8449145 TI - Methodological approach in the study of anticancer drug metabolism: qualitative considerations. PMID- 8449146 TI - Drug metabolism in the nasal cavity: relevance to toxicology. PMID- 8449147 TI - Drug metabolism and the Gordon Research Conferences. PMID- 8449148 TI - Chemistry and biology of heme. Effect of metal salts, organometals, and metalloporphyrins on heme synthesis and catabolism, with special reference to clinical implications and interactions with cytochrome P-450. AB - Although free porphyrins occur in nature in small quantities, no known function has been assigned to them. In contrast, heme and cobalamin, which are Fe and Co chelates of porphyrins or porphyrin derivatives, respectively, carry out crucial biological functions. Heme is the prosthetic group for a number of hemoproteins. These include myoglobin and hemoglobin, which carry out oxygen binding or transport; mitochondrial cytochromes aa3, b, c, and c3, which are important in transferring electrons; microsomal cytochrome P-450, which catalyzes mixed function oxidations; catalase, which decomposes H2O2; peroxidase, which activates H2O2; and tryptophan pyrrolase, which catalyzes the oxidation of tryptophan. Recently, heme has also been shown to be the prosthetic group of prostaglandin and peroxide synthetase and indoleamine dioxygenase. The elegant studies of the biochemical pathway for the formation of heme demonstrated the arrangement in the porphyrin macrocycle of the carbon and nitrogen atoms originating from the eight glycine and the succinic acid molecule that are the precursors of porphyrins. There are eight enzymes involved in the synthesis of heme. The first and last three of these enzymes are localized in mitochondria, while the intermediate enzymes are localized in cytosol. The catalytic site of HMOX recognizes metalloporphyrins with central metal atoms other than iron; it favors some of these metalloporphyrins over heme as a potential substrate, sometimes by a large factor, permitting the synthetic heme analogue to serve as a potent competitive inhibitor of HMOX reaction. Since these synthetic metalloporphyrins do not bind molecular oxygen, they are not metabolically degraded by ring rupture and do not add to the body pool of bile pigment. One possible consequence of this competitive inhibition of heme degradation is suppression of bile pigment formation to such a degree that excessive plasma levels of bilirubin may be diminished. The studies of Drummond and Kappas (1981) and later studies in rats, mice, monkeys, and man, and also our studies have proved the latter phenomenon. The compound does not appear to affect the metabolic disposition of preformed bilirubin but inhibits biliary bilirubin excretion derived from the metabolism of endogenous or exogenous heme. Whether some of the effect of Sn-PP on naturally occurring or experimentally induced jaundice in animals reflects diversion of heme to nonheme to oxygenase-dependent pathways of heme metabolism, or whether a pathway which is normally latent becomes activated concurrent with HMOX inhibition is not known.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8449149 TI - [Report of a mother's experiences]. PMID- 8449150 TI - [Porphyrias]. PMID- 8449151 TI - [Teaching of children with diabetes mellitus]. PMID- 8449152 TI - [Room nursing. Introduction and first experiences]. PMID- 8449153 TI - [Grinding one's teeth. "... they will cry and gnash their teeth" (Math.8, 12)]. PMID- 8449154 TI - [The various preventive areas of the health system. Clearly shown in the oncologic area]. PMID- 8449155 TI - [Shortening of the work time as a stress balance in nursing--2 direction giving ideas from Austria and the Federal Republic]. PMID- 8449156 TI - [The hospitalized child. Concept of a lesson]. PMID- 8449157 TI - [Effect of the thyroid hormones on the metabolism]. PMID- 8449158 TI - [Screening of newborns]. PMID- 8449159 TI - [Phenylketonuria and hyperphenylalaninemia]. PMID- 8449160 TI - [The German phenylketonuria study. Description of a longitudinal study and its results]. PMID- 8449161 TI - [Diet therapy in phenylketonuria]. PMID- 8449162 TI - [Mucoviscidosis. Clinical aspects and treatment]. PMID- 8449163 TI - [Galactosemia]. PMID- 8449164 TI - [Maple syrup urine disease]. PMID- 8449165 TI - A clinicophysiologic study of central and peripheral motor conduction in hereditary demyelinating motor and sensory neuropathy. AB - Central and peripheral motor nerve conduction were analyzed in 13 patients with hereditary demyelinating motor and sensory neuropathy using central magnetic stimulation and peripheral electrodiagnostic techniques. All patients showed a marked decrease in peripheral nerve conduction velocity. In 11 patients, the central motor conduction time was slightly prolonged but in 2 it was markedly prolonged suggesting dysfunction of the corticospinal tract. These two patients exhibited marked weakness and atrophy of distal muscles without clinical signs of upper motor neuron dysfunction, which was considered to be masked by the lower motor neuron disorder. This study suggests that in some patients with hereditary demyelinating polyneuropathy central as well as peripheral nerve fibers may be affected. PMID- 8449166 TI - Malignant tumour of the psoas: another cause of meralgia paraesthetica. AB - Contrasting the more benign causes known for meralgia paraesthetica we report a case due to a malignant tumour of the psoas muscle. We discuss the use of sensory nerve conduction study and somatosensory evoked potentials of the lateral femoral cutaneous nerve as well as needle EMG and diagnostic nerve block to detect the site of the lesion along its course. This appears of major importance, as causes located above the inguinal ligament can bear a more serious prognosis than the ones below. PMID- 8449167 TI - The role of body size in somatosensory testing. AB - To try to replicate our earlier findings of body size influences in somatosensory testing we measured thresholds of heat pain, warmth, cold and vibration in 66 young, normal-weight women. Our assumption was that true body measure effects have to be demonstrable even in a sample limited with regard to age and sex and without extreme body size variation (which may be linked to pathology). In the present sample, body size (a linear combination of height and weight) did not have a very strong relation with any of the somatosensory thresholds (slightly stronger for the warmth and cold thresholds than for the heat pain and vibration thresholds). Hence, we could not fully replicate our earlier findings of marked body size effects on warmth and cold thresholds obtained in a sample without such limits. A measure of the body fat content seemed to have some explanatory power, but only for the vibration thresholds. We conclude that body measures, age and sex may be confounded in a way that cannot always be sorted out by a posteriori analyses and should therefore be treated a priori as independent variables for purposes such as establishing normal values in somatosensory testing. PMID- 8449168 TI - Quantitative sensory threshold testing in patients with multiple sclerosis. AB - Cutaneous thresholds for vibratory and thermal stimuli were quantitated at the index finger and great toe of twelve patients with definite multiple sclerosis. Nine of 12 (75%) patients had abnormalities to either modality, especially at the great toe, where 48% of vibratory and 17% of thermal thresholds were abnormal. Of ten patients undergoing somatosensory evoked potential (SSEP) testing, 8 (80%) had abnormal median and 9 (90%) had abnormal tibial studies. While more experience is needed to determine the sensitivity of quantitative sensory threshold testing in this application, this simple, noninvasive technique appears to correlate both with clinical and SSEP findings. PMID- 8449169 TI - The effect of temperature on antidromic median sensory conduction. AB - It has been well documented that sensory nerve conduction studies are influenced by many factors. Twenty-two healthy subjects were electrophysiologically evaluated to measure the onset latency, peak latency and amplitude (baseline to negative peak) after cooling the non-dominant hand. The distal onset latency was prolonged by 0.06 msec/degrees C, peak latency by 0.1 msec/degrees C and the amplitude was increased by 1.8 microV/degrees C by cooling hand skin temperature from 34 to 26 degrees C. These results can be used to extrapolate the value at normal physiologic skin temperature for the subject whose temperature is lower than normal. The results were compared with previous reports. PMID- 8449170 TI - The importance of neurophysiological evaluation of plexus brachialis injury caused by open heart surgery. AB - The risk of brachial plexus injury as a complication of coronary bypass operation should be emphasized since the number of coronary operations is rapidly increasing. We describe six patients who developed symptoms consistent with brachial plexus injury after coronary bypass surgery. Four out of six patients had definitive electroneuromyography (ENMG) abnormalities consistent with an acute injury in the brachial plexus. Abnormal somatosensory evoked potential (SEP) was seen in two patients studied. Two of our patients suffered from diabetic polyneuropathy, which even seems a predisposing factor for plexus brachialis injury and to prolong the duration of disability. Based on literature and our own experience we strongly recommend the use of ENMG and SEP to all patients who have any postoperative neurogenic symptoms in the upper extremities. These methods confirm the site of the nerve damage, e.g., differentiate brachial plexus injury from peripheral ulnar nerve lesion, and help to predict the outcome. PMID- 8449171 TI - The influence of interelectrode distance on bipolar recording of sensory nerve action potential. A mathematical study. AB - Bipolar recording of Extracellular Single Fiber Action Potential (ESFAP) and Sensory Nerve Action Potential (SNAP) were simulated mathematically. The study attempts to analyze the influence of interelectrode distance on the amplitude of bipolar recordings. Simulations of bipolar recordings of ESFAP and SNAP presented four major peaks whose relations changed with the distances between the electrodes which compose the derivation. The maximum amplitude of bipolar ESFAP was produced at similar interelectrode distances for the range of fibers studied in clinical practice. In bipolar recordings of SNAP, the interelectrode distance producing the maximum amplitude increases with the distance between the place of stimulation and the place of recording. PMID- 8449172 TI - Posterior tibial somatosensory evoked potentials from distal, middle and proximal lower limb stimulation. A comparative study. PMID- 8449173 TI - Protein dynamics: conformational disorder, vibrational coupling and anharmonicity in deoxy-hemoglobin and myoglobin. AB - In this work we study the temperature dependence of the Soret band lineshape of deoxymyoglobin and deoxyhemoglobin, in the range 300-20 K. To fit the measured spectra we use an approach originally proposed by Champion and coworkers (Srajer et al. 1986; Srajer and Champion 1991). The band profile is modelled as a Voigt function that accounts for the coupling with low frequency vibrational modes, whereas the coupling with high frequency modes is responsible for the vibronic structure of the spectra. Moreover, owing to the position of the iron atom out of the mean heme plane, inhomogeneous broadening brings about a non-Gaussian distribution of 0-0 electronic transition frequencies. The reported analysis enables us to isolate the various contributions to the overall bandwidth, and their temperature dependence points out the relevance of low frequency vibrations and of large scale anharmonic motions starting at temperatures higher than 170 K. Information on the mean iron-heme plane distance and on its temperature dependence, as well as on the heme pocket conformational disorder, is also obtained. PMID- 8449174 TI - Interaction of the trp repressor with trp operator DNA fragments. AB - The interaction of the trp repressor with several trp operator DNA fragments has been examined by DNA gel retardation assays and by circular dichroism, in the absence and presence of the corepressor L-tryptophan. The holorepressor binds stoichiometrically to both the trpO and aroH operators, forming 1:1 complexes. In the presence of excess protein, additional complexes are formed with these operator fragments. The relative electrophoretic mobilities of the 1:1 complexes differ significantly for trp and aroH operators, indicating that they differ substantially in gross structure. A mutant trp operator, trpOc, has low affinity for the holorepressor, and forms only complexes with stoichiometries of 2:1 (repressor: DNA) or higher, which have a very low electrophoretic mobility. Specific binding is also accompanied by a large increase in the intensity of the near ultraviolet circular dichroism, with only a small blue shift, which is consistent with significant changes in the conformation of the DNA. Large changes in the chemical shifts of three resonances in the 31P NMR spectrum of both the trp operator and the aroH operator occur on adding repressor only in the presence of L-tryptophan, consistent with localised changes in the backbone conformation of the DNA. PMID- 8449175 TI - Determination of conformational transition rates in the trp promoter by 1H NMR rotating-frame T1 and cross-relaxation rate measurements. AB - Rotating-frame relaxation measurements have been used in conjunction with spin spin relaxation rate constants to investigate a conformational transition previously observed in the -10 region of the trp promoter d(CGTACTAGTTAACTAGTACG)2 (Lefevre, Lane, Jardetzky 1987). The transition is localised to the sub-sequence TAAC, and is in fast exchange on the chemical shift time-scale. The rate constant for the exchange process has been determined from measurements of the rotating-frame relaxation rate constant as a function of the spin-lock field strength, and is approximately 5000 s-1 at 30 degrees C. Measurements have also been made as a function of temperature and in two different magnetic fields: the results are fully consistent with those expected for the exchange contribution in a two-site system. A similar transition has been observed in d(GTGATTGACAATTA).d(CACTAACTGTTAAT), which contains the -35 region of the trp promoter. This has been investigated in the same way, and has been found to undergo exchange at a faster rate under comparable conditions. In addition, the cross-relaxation rate constants for Ade C2H-Ade C2H pairs have been measured as a function of temperature, and these indicate that certain internuclear distances in YAAY subsequences increase with increasing temperature. These changes in distance are consistent with a flattening of propellor twist of the AT base-pairs. The occurrence of conformational transitions in YAAY subsequences depends on the flanking sequence. PMID- 8449176 TI - The effect of progesterone and its metabolite 5 alpha-pregnan-3 alpha-ol-20-one on focal epileptic seizures in the cat's visual cortex in vivo. AB - The acute effects of progesterone and its brain metabolite 5 alpha-pregnan-3 alpha-ol-20-one (3 alpha-OH-DHP) on focal epileptic seizures in the cat's visual cortex was studied in vivo using an unanesthetized cervaux-isole preparation. This model made it possible to study in parallel the effect of the drugs on ictal activity and synaptic transmission. A dose-dependent increase in seizure threshold was observed after i.v. injections of both 3 alpha-OH-DHP and progesterone, 3 alpha-OH-DHP being about 20 times as potent as the latter. I.v. injections of 3 alpha-OH-DHP 1.0 mg/kg increased the median seizure threshold to 265% of baseline. While 3 alpha-OH-DHP exerted an immediate effect on seizure thresholds, the maximal effect of progesterone was delayed about 20 min. Concerning the mechanisms underlying the antiepileptic effect, three changes occurred within the effective dose range: (1) a small, but significant reduction in the presynaptic nerve volleys, (2) a reduction in the postsynaptic excitatory field potentials in the dorsal lateral geniculate nucleus and cortex, and (3) an enhanced postsynaptic inhibition. Taken together, these observations point to both pre- and postsynaptic effects, supporting the hypothesis of a barbiturate like mechanism of action of progesterone and its brain metabolites. PMID- 8449177 TI - Social conflict situations in rats differentially affect the development of amygdala kindling. AB - Clinical studies revealed an association between the occurrence of convulsions and stress. However, the direction of such relations and their mechanisms are not quite clear. The present study investigated the influence of stress-inducing agonistic conflict situations on the progressive process of kindling epileptogenesis induced by daily tetanic stimulation of the amygdala. Whereas repeated exposure to defeat in an agonistic setting did not affect the development of amygdala kindling, repeated victory experiences resulted in a significant retardation of the kindling process. Moreover, the kindling process was retarded to a greater extent in rats that quickly displayed offensive behavior and won the confrontation. Possible underlying mechanisms and biological substrates are discussed in terms of the ability of the individual to control or cope with the nature of the stressor. PMID- 8449178 TI - MK801 pretreatment reduces kainic acid-induced spontaneous seizures in prepubescent rats. AB - MK801 is a noncompetitive blocker of N-methyl-D-aspartate receptors which has antiepileptic properties. To evaluate whether MK801 pretreatment in immature rats affects the future spontaneous recurrent seizure (SRS) rate or seizure susceptibility in a model of limbic epilepsy, MK801 (0.2 or 1.0 mg/kg, i.p.) or saline was administered to prepubescent rats 30 min prior to kainic acid (KA; 10 mg/kg, i.p.). With or without MK801 pretreatment, KA caused prolonged status epilepticus. SRS rate over the next 4 weeks, as assessed by intermittent video monitoring, was significantly lower in MK801 treated rats than in those which received KA alone. In addition, fewer MK801 treated rats (43%) developed SRS than those which got KA alone (88%). Susceptibility to generalized seizures was then tested using the volatile convulsant flurothyl; at both doses of MK801, flurothyl seizure latency was significantly greater in pretreated animals. These results show that MK801 pretreatment prior to KA induced status epilepticus reduces subsequent SRS frequency and flurothyl seizure susceptibility, while not substantially altering the acute epileptogenic effects of KA. PMID- 8449179 TI - Are differences in dorsal hippocampal kindling related to amygdala-piriform area excitability? AB - It has been suggested that several structures associated with the amygdala piriform (A-P) area are important, if not critical, for convulsive generalization of limbic seizures. In experiment 1, when examining the development of convulsive seizures kindled from the dorsal hippocampus (cornus ammonis; DH), a broad range of kindling rates was observed. Independent of electrode location within the hippocampus, kindling rates were correlated positively with both local and, more dramatically, distant excitability (measured by the duration of the primary and secondary hippocampal afterdischarges, respectively) at all stages of epileptogenesis. Because kindling rates were bimodally distributed, we bisected the distribution into 'faster' and 'slower' kindling rats. Here we examined the magnitude of both electrophysiological and behavioral differences between 'faster' and 'slower' rats and their changes over time. The 'faster' rats had longer primary and secondary afterdischarge (AD) durations than 'slower' rats throughout all stages of kindling. With the appearance of generalized convulsions, the 'faster' rats showed longer latencies to clonus onset, with longer clonus and AD durations than 'slower' rats. Also, the generalized convulsions of 'faster' rats appeared during a much enlarged secondary AD period, while 'slower' rats convulsed during primary AD. In both groups, convulsions were invariably associated with increased discharge in A-P associated structures. We interpreted the differences between 'faster' and 'slower' DH rats to reflect genetic differences in excitability in both local and A-P associated structures. If the DH kindling profile of the 'faster' rats differed from 'slower' rats largely because of naturally greater excitability in A-P associated structures, then experimentally increased excitability in those structures (via amygdala kindling) in a random sample of rats should duplicate much of the 'faster' DH kindling profile. In experiment 2, this outcome was observed. In conclusion, we suggest that either natural or induced differences in the excitability of A-P associated structures affect both the genesis and the profile of convulsive generalization of limbic kindled seizures. PMID- 8449180 TI - Cortical self-regulation in patients with epilepsies. AB - The present study aimed at investigating to what extent the regulation of excitability in cortical networks, as indicated by surface-negative slow cortical potentials (SCPs), is impaired in epileptic patients and to what extent training of SCP self-regulation by means of biofeedback and instrumental learning procedures might affect seizure frequency. Twenty-five patients suffering from drug-refractory epilepsies (complex focal, grand mal, and absence type of seizures) participated in 28 1-h sessions of feedback and instrumental conditioning of their SCPs. Subjects' EEGs were obtained from the vertex. Depending on discriminative stimuli DC shifts towards increased or suppressed negativity relative to the pre-trial baseline were demonstrated by on-line visual feedback during intervals of 8 s each; each session comprised 110 trials. While performance on the SCP self-regulation task was initially below normal (as compared to healthy subjects), significant increases in SCP control were achieved by the patients across the 28 training sessions. In 18 patients at least 1-year follow-up data are available. Changes in seizure frequency were related to transfer of SCP control with six of the patients becoming seizure-free. Age affected the ability to acquire SCP control and its impact on seizure frequency. PMID- 8449181 TI - Platelet GABA-transaminase in epileptic children: influence of epilepsy and anticonvulsants. AB - The relationship between platelet GABA-transaminase (GABA-T) activity and either epilepsy or its treatment has been studied in 281 epileptic children: 55 were newly diagnosed untreated patients and 226 were chronically receiving anticonvulsants (154 in monotherapy and 72 in polytherapy). Results were compared with those from 48 control children. Untreated children had a GABA-T activity of 9.1 +/- 3.7 pmol/min/mg protein, lower than the control group (10.6 +/- 3.8 pmol/min/mg, P < 0.05), whereas treated epileptic children had higher values (11.9 +/- 6.3 pmol/min/mg) than those untreated (P < 0.01). In untreated children, the seven with absences and the nine with simple partial seizures had a GABA-T activity of 6.9 +/- 3.3 and 7.8 +/- 3.2 pmol/min/mg, respectively, lower than the control group (P < 0.05). In treated patients, those receiving valproate (VPA) in monotherapy had a GABA-T activity of 15.3 +/- 7.5 pmol/min/mg, higher than both the control group and the untreated children (P < 0.001). All patients receiving VPA in mono- or polytherapy had a higher activity than those receiving other anticonvulsants (16.4 +/- 8.4 vs. 9.9 +/- 3.9 pmol/min/mg, P < 0.001), the activity in Lennox syndrome and myoclonic epilepsies being significantly higher than in those with absences and partial epilepsy. GABA-T activity did not correlate with doses or trough steady-state serum levels of VPA. Platelet GABA-T could be useful as a peripheral marker of GABAergic alterations and GABAergic effects of antiepileptic drugs in epileptic patients. PMID- 8449182 TI - Analysis of electrocardiographic changes in status epilepticus. AB - The high mortality associated with status epilepticus (SE) has been hypothesized to result partially from neurologically induced changes in cardiac function. To test this hypothesis, we reviewed electrocardiograms of 60 patients presenting in status epilepticus. Sequential electrocardiograms before, during and after ictal episodes were compared to define changes from baseline studies. 58.3% of the SE patients (N = 35) exhibited significant abnormalities on electrocardiograms obtained within 24 h of status epilepticus. Specific electrocardiographic changes included arrhythmias, axis changes, conduction abnormalities and ischemic patterns. All of these abnormal ECG changes met generally accepted cardiologic standards for a high risk of myocardial dysfunction or ischemia. The association of ECG changes with mortality was statistically significant. These results indicate that a significant proportion of SE patients are at risk for cardiac dysfunction and that close monitoring of cardiac function is indicated during and after SE. PMID- 8449183 TI - Normal reproductive neuroendocrinology in the female. AB - The reproductive axis in women comprises a number of components that must function in a highly orchestrated manner for reproductive potential to be optimal. The neuroendocrine components of this axis, including the hypothalamus and the pituitary gland, are central to this system. Within the hypothalamus, the specialized neuronal system responsible for synthesizing and secreting gonadotropin-releasing hormone (GnRH) is itself modulated by a number of peptide and biogenic amine neurotransmitters that mediate feedback signals of ovarian origin. The luteinizing hormone and follicle-stimulating hormone secreting anterior pituitary gonadotropes perceive and transduce neural input in the form of GnRH, but are themselves also modulated by the ambient gonadal hormone concentrations. The authors review the physiologic relevance of the pulsatile nature of the GnRH signal, and some proposed mechanisms through which these signals are stimulated and modulated and subsequently perceived and transduced by gonadotropes. PMID- 8449184 TI - Male hypogonadotropic hypogonadism. AB - Hypogonadotropic hypogonadism in the male is caused by alterations in gonadotropin-releasing hormone secretion or through abnormal pituitary secretion of luteinizing hormone or follicle-stimulating hormone. Recent studies in animal and human models have demonstrated possible pathophysiologic explanations for the occurrence of some GnRH-deficient states. It is critical to ascertain whether such patients represent a variant of normal or have true hypogonadotropic hypogonadism. Recent developments in both diagnostic techniques and hormonal treatment increase the chances of a correct diagnosis and successful treatment outcome. PMID- 8449185 TI - Hypothalamo-pituitary gonadal axis in chronic renal failure. AB - Chronic renal failure causes extensive neuroendocrine disturbance, including marked hypothalamo-pituitary dysfunction which is reversed by renal transplantation but not dialysis. Gonadal dysfunction in uremia is manifest as delayed puberty in adolescents; as testicular atrophy, hypospermatogenesis, infertility, impotence in men; and as anovulation, infertility, and menstrual disturbance in women. Gonadal steroidogenesis and gametogenesis are impaired and gonadotropin levels are increased. In addition to evidence of defects in pituitary and gonadal function, increasing evidence indicates the importance of alterations in hypothalamic regulation of pituitary-gonadal function in the pathogenesis of uremic hypogonadism. Experimental uremia induced by subtotal nephrectomy in mature rats causes gonadal dysfunction, which is principally due to aberrant neuroendocrine regulation of GnRH secretion involving inhibition of GnRH secretion, hypersensitivity to negative testicular feedback, and resistance to naloxone, a triad of features termed ontogenic regression. PMID- 8449186 TI - Clinically nonfunctioning pituitary adenomas. AB - Clinically nonfunctioning pituitary adenomas do not produce a readily recognizable clinical syndrome attributable to hormonal secretion. Any kind of pituitary adenoma may be clinically nonfunctioning, but gonadotroph and thyrotroph adenomas are more likely to be nonfunctioning, lactotroph adenomas less likely, and somatotroph and corticotroph adenomas least likely. Clinically nonfunctioning adenomas usually come to medical attention when they become so large that they cause neurologic symptoms, especially visual impairment. Although they are difficult to recognize clinically, they can be identified in vivo by measurement of basal and TRH-stimulated concentrations of follicle-stimulating hormone, luteinizing hormone, thyroid-stimulating hormone, and their subunits. They can also be recognized in vitro by secretion in culture, immunospecific staining, and probing for mRNAs. Primary treatment is usually transsphenoidal surgery, and adjunctive treatment may include supervoltage radiation, and occasionally, pharmacologic agents. PMID- 8449187 TI - Female hypogonadotropic hypogonadism. Hypothalamic amenorrhea syndrome. AB - The neuroendocrine-metabolic repertoire governing the reproductive cyclicity in women can be interrupted by a variety of social, environmental, nutritional, and psychological aberrations. Clinical conditions including exercise-related and psychogenic amenorrhea, and desynchronization of biological rhythms in the development of hypothalamic gonadotropin-releasing hormone dysfunction are discussed. Clinical and laboratory evaluations and modes of management are presented. PMID- 8449188 TI - Lactational amenorrhea. AB - There is no doubt that suckling can cause a substantial delay in the resumption of fertility postpartum in all societies regardless of nutritional status. The variability in duration of infertility is directly related to the different patterns of suckling, an uncontrollable variable specific to the mother and child. Resumption of fertility proceeds in two parts, an initial phase of amenorrhea in which ovarian follicle growth is suppressed or attenuated followed by a resumption of menstrual cycles often associated with inadequate luteal function contributing to the reduced fertility of lactating menstruating women. Suckling appears to suppress the normal pattern of pulsatile release of GnRH and hence LH and prevents the normal growth of follicles. The normal positive feedback effect of estrogen on LH release is abolished, and estradiol exerts an enhanced negative feedback effect on both LH and FSH. Thus, while suckling continues, any follicle that starts to develop and secrete estradiol will inhibit further LH release and therefore stop growing. When suckling declines, the pulsatile pattern of LH returns to normal, sensitivity to estrogen negative feedback declines, and follicle growth can continue and ovulation will occur. Opiates do not appear to be mediators of the suckling-induced suppression of GnRH or the release of prolactin in women. There is no clear role for prolactin per se or nutritional status in the suppression of ovarian activity postpartum. Thus, while the suppression of fertility in breast-feeding women plays an extremely important role in limiting populations, the mechanism whereby the suckling stimulus from the nipple causes the disruption in GnRH release from the hypothalamus remains to be elucidated. PMID- 8449189 TI - Neuroendocrine physiology of the normal male gonadal axis. AB - The normal male reproductive axis requires coordinate control of hypothalamo pituitary testicular components. Such coordinate control is accomplished by specific feedback regulation. Here, we have reviewed the physiology of neuroendocrine feedback controls operating within the healthy male reproductive axis. PMID- 8449190 TI - Impedance cardiography during exercise in patients with coronary heart disease. AB - Impedance cardiography may be a simple way of assessing left ventricular performance during exercise. Measurements were therefore made during exercise testing in 102 consecutive male patients with suspected coronary disease prior to cardiac catheterization. These were subsequently divided into four groups: group A, normal; group B, 1- or 2-vessel disease; group C, 3-vessel disease (groups A, B, and C, left ventricular ejection fraction (LVEF) > 55%); and group D, 3-vessel disease with LVEF < 55%. Immediately after peak exercise several impedance measures were significantly correlated with resting LVEF, especially dZ/dtmax (R = 0.41, P < 0.001) and Heather index (R = 0.46, P < 0.001). Heather index was the best discriminator between the disease groups with mean values (95% confidence intervals) of 25.7 (22.2-29.2) (group A), 21.9 (20.6-23.2) (group B), 18.4 (16.2 20.6) (group C), and 15.3 (10.3-20.3) omega s-2 (group D) but there was considerable overlap between groups (risk ratios 1.17 and 3.15 for any and triple vessel coronary disease respectively). Measurements were therefore of little diagnostic value. The majority of patients with abnormal responses could be identified more simply by their poor exercise tolerance or abnormal blood pressure response. PMID- 8449191 TI - An analysis of the relationship between central aortic and peripheral upper limb pressure waves in man. AB - Amplification of the pressure pulse between central and peripheral arteries renders pressure values in the upper limb an inaccurate measure of ascending aortic (AA) pressure. Accuracy could be improved by allowance for such amplification. Transfer functions (TF) for pressures between AA and brachial artery (BA):(BATF) and between AA and radial artery (RA):(RATF) were derived from high-fidelity pressure recordings obtained at cardiac catheterization in 14 patients under control conditions, and after sublingual nitroglycerine 0.3 mg. There was no significant difference in BATF under control conditions and with nitroglycerine; hence results were pooled. Control and nitroglycerine results were also pooled to obtain a single RATF. BATF and RATF moduli peaked at 5 Hz and 4 Hz, reaching 2.5 and 2.8 times the value at zero frequency respectively. Frequency-dependent changes in modulus and phase of BATF and RATF were attributable to wave travel and reflection in the upper limb. BATF and RATF were compared to published transfer functions and those derived from analysis of aortic and brachial or radial pressure waves in previous publications. Results were similar. Our BATF and RATF were used to synthesize AA pressure waves from published peripheral pulses. Correspondence was close, especially for systolic pressure which differed by 2.4 +/- 1.0 (mean +/- SEM) mmHg, whereas recorded systolic pressure differed by 20.4 +/- 2.6 (mean +/- SEM) mmHg between central and peripheral sites. Results indicate that in adult humans a single generalized TF can be used with acceptable accuracy to determine central from peripheral pressure under different conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8449192 TI - Non-invasive magnetocardiographic localization of ventricular pre-excitation in the Wolff-Parkinson-White syndrome using a realistic torso model. AB - This study was performed to evaluate the accuracy of magnetocardiography in non invasive localization of the ventricular pre-excitation site in patients suffering from the Wolff-Parkinson-White (WPW) syndrome. Twelve WPW patients were studied, in whom the pre-excitation caused serious supraventricular arrhythmias refractory to drug therapy. Magnetocardiographic measurements were performed in a magnetically shielded room, and non-invasive localization was computed from preprocessed magnetic signals using a current dipole source in a realistically shaped digital torso. All patients underwent intra-operative multicatheter mapping and subsequent dissection of the accessory atrioventricular connection. The intra-operative localization results were marked on magnetic resonance images of the heart, where magnetocardiographic results were also superimposed to allow comparison. The average of the three-dimensional differences between the magnetocardiographic and the invasive results was 2.1 +/- 0.9 cm. In all cases, the computed localization result was in the same or adjacent anatomical region as the intra-operative result. The present results show that the magnetocardiographic method using a realistic torso model is capable of localizing pre-excitation sites with sufficient accuracy to provide extra information so that non-pharmacological therapeutic interventions can be applied. PMID- 8449193 TI - Myocardial indium-111 antimyosin uptake in patients with idiopathic dilated cardiomyopathy: its relation to haemodynamics, histomorphometry, myocardial enteroviral infection, and clinical course. AB - The myocardial uptake of indium-111 antimyosin indicates the presence of ongoing myocyte damage. To evaluate the role of this finding in patients with idiopathic dilated cardiomyopathy (IDC), 36 patients were studied by planar and SPECT antimyosin imaging. The diagnosis of IDC was based on coronary angiography and left ventricular endomyocardial biopsy. The antimyosin scan was evaluated qualitatively from SPECT images and assessed quantitatively by a count density index (CDI) which measured the tracer activity over the heart relative to the lung and sternal region (normal value less than 1.20). Group 1 consisted of 13 patients (36%) with an increased myocardial antimyosin uptake, while 23 patients had a normal antimyosin scan (group 2). Clinical data, pulmonary artery pressures, gated blood pool ejection fraction and histomorphometry of endomyocardial biopsies were similar in both groups. During a follow-up of 21 +/- 12 months there were two cardiac deaths in group 1 and 10 deaths in group 2 (P = 0.12). The 2-year survival rate was 81% and 59%, respectively. During follow-up, there was no significant change in haemodynamic parameters in either group, but there was a slight improvement in functional NYHA class in group 1 (P < 0.05). No association was found between the presence of myocardial enterovirus infection, determined in 17 patients by in situ hybridization and the antimyosin scan (P = 0.5 g). Myocardial antimyosin uptake was found in a high percentage of patients with IDC, indicating ongoing myocyte damage. This finding was not related to any clinical, haemodynamic, morphological parameter, or enterovirus infection. Myocyte damage is a distinct feature in a subgroup of patients with IDC unrelated to any known causes of myocellular destruction. This subgroup showed a trend towards a more favourable clinical outcome. PMID- 8449194 TI - Coronary reserve, extent of coronary disease, recurrent angina and ECG changes during pain in the in-hospital prognosis of acute coronary syndromes. AB - The prognostic value of recurrent angina, severity of coronary disease, ECG changes during pain and coronary reserve (ischaemic threshold measured by atrial pacing: heart rate with ST segment shift = 1 mm), was evaluated in 383 consecutive patients with acute coronary syndromes. Univariate analysis showed a significant relationship between occurrence of complications (death, infarction or coronary surgery) and number of anginal episodes, extent of coronary disease, ischaemic threshold and ST depression with pain. A multivariate analysis indicated that the first three parameters were the main independent predictors. Coronary reserve was reduced (threshold < or = 150 beats.min-1) in 83% of patients who had a myocardial infarction (40), in 91% of those who died (11), in 87% of those who underwent coronary surgery (52) and in 47% of uncomplicated cases (301). Also, a low ischaemic threshold was associated with a larger number of anginal episodes than a high threshold (< or = 130 beats.min-1, 6.1 +/- 5.6 vs > 150 beats.min-1, 2.9 +/- 4.1, P < 0.0001), and in complicated patients with one , two- or three-vessel disease ischaemic threshold (137.3 +/- 21.2, 133.3 +/- 18.9, and 135.1 +/- 21.2 beats.min-1, respectively) was lower than in the uncomplicated ones (153.4 +/- 20.1, P < 0.005; 148.2 +/- 19.1, P < 0.005; and 139.2 +/- 23.0 ns, beats.min-1). A threshold < 150 beats.min-1 and ECG changes during pain identified the subset with the highest risk for complications (59/137, 45%), whereas a threshold > 150 beats.min-1 and absence of pain or ECG changes during pain identified those with the lowest risk (5/109, 5%, P < 0.001). Thus, our findings document the prognostic significance of coronary reserve for in-hospital complications in patients with acute coronary syndromes and confirm the prognostic value of previously known risk markers. They also indicate that some of them may be significantly influenced by the status of coronary reserve. PMID- 8449196 TI - Platelet function, thrombin and fibrinolytic activity in patients with heart failure. AB - Assays which detect the release of platelet-specific proteins and of peptides during thrombogenesis and are considered markers of activation of platelets and the coagulation system have recently been developed. This study was designed to utilize these haemostasis-related markers to test the hypothesis that a prethrombotic state is related to the presence, aetiology and severity of heart failure. Seventy patients with heart failure were evaluated and data were compared with 36 normal volunteers and 41 patients with coronary artery disease without heart failure (CAD). Thrombogenesis was documented using assays which measure platelet function, thrombin activity and fibrinolysis. Platelet function was measured by determining plasma concentrations of platelet factor 4 (PF4) and beta-thromboglobulin (BTG). Thrombin-antithrombin III complexes (TAT) and fibrinopeptide A (FPA) were determined to evaluate thrombin activity. Fibrinolytic activity was assessed by measuring D-Dimer levels. Patients with heart failure, when compared to normals, had increased plasma levels of BTG (89 +/- 62 IU.ml-1 vs 50 +/- 59 IU.ml-1, P < 0.01), TAT (4.6 +/- 4.3 micrograms.l-1 vs 2.3 +/- 0.64 micrograms.l-1, P < 0.005), and D-Dimer levels (506 +/- 444 IU.ml 1 vs 191 +/- 144 IU.ml-1, P < 0.0001). Patients with heart failure, when compared to the CAD group, had increased plasma levels of D-Dimer (506 +/- 444 ng.ml-1 vs 191 +/- 144 ng.ml-1, P < 0.05). Aetiology of heart failure did not affect these measurements. Patients with severe heart failure, as determined by high plasma norepinephrine concentration or low ejection fraction, were more likely to have activation of platelets and the coagulation system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8449195 TI - Acute closure during coronary excimer laser angioplasty and conventional balloon dilatation: a comparison of management outcome and prediction. AB - Of 523 consecutive patients undergoing elective percutaneous transluminal coronary angioplasty (PTCA) and 83 patients treated with coronary excimer laser angioplasty (ELCA), 17 (3.3%) had in-laboratory occlusion following PTCA and 25 (30%) following ELCA; they were enrolled into a prospective study. Successful management (reopened vessel, patency at repeat angiography within 24 h, no death, no myocardial infarction (MI), no emergency bypass surgery) including repeat lasing, subsequent PTCA, use of intracoronary nitroglycerin or streptokinase was achieved in 24 (96%) of the 25 patients with acute occlusion during ELCA. An anterior MI occurred in one patient of the laser group. Repeat balloon dilatation was successfully performed in seven of the 17 patients (41%) with acute closure during PTCA. Among the 10 patients with persistent occlusion after PTCA, five developed a limited myocardial infarction (35%). One patient required emergency CABG, and died peri-operatively. Severe spasm prior to occlusion defined by a new coronary flow depression without evidence of dissection or thrombus showed a significant positive association with acute occlusion during ELCA (P = 0.0008). Thus, in contrast to occlusion during PTCA, subsequent balloon dilatation was successfully performed in the majority of patients with acute occlusion during ELCA, implying that different underlying mechanisms are responsible for this complication. In this limited patient group, occlusion after excimer laser angioplasty was much more frequent than closure during PTCA, but was infrequently associated with major events such as myocardial infarction or death. PMID- 8449197 TI - Prognostic value of exercise radionuclide angiography in low risk acute myocardial infarction survivors. AB - Patients with an uneventful course during hospital stay, which represent from 30 to 50% of all myocardial infarction survivors, still have an incidence of new coronary events up to 7% during the first year of follow-up. To assess the value of radionuclide angiography in predicting new coronary events in this low risk population, 93 patients without evidence of left ventricular failure or recurrent postinfarction angina underwent rest and exercise radionuclide angiography and treadmill exercise testing before hospital discharge. During follow-up (16 +/- 5 months, range 12 to 32) 14 patients developed new coronary events: two patients died, four had a new myocardial infarction and the remaining eight had unstable angina. There were no differences regarding clinical variables, the results of the exercise test and the resting ejection fraction, between patients with or without new coronary events; however, patients without events during follow-up exercised longer during both exercise treadmill test and exercise radionuclide angiography. Resting end-diastolic and end-systolic volume indexes were higher in patients presenting coronary events (122 +/- 50 vs 92 +/- 32 ml.m-2, P < 0.05, 69 +/- 47 vs 47 +/- 26 ml.m-2, P < 0.05). These patients also had a higher incidence of wall motion abnormalities in more than one area (64 vs 28%, P < 0.02). During exercise, ejection fraction increased significantly in patients with an uneventful outcome (49 +/- 13 to 56 +/- 14%, P < 0.01), while it did not change in their counterparts (46 +/- 14 to 45 +/- 14%, NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8449198 TI - Coronary artery disease after heart transplantation: non-invasive evaluation with exercise thallium scintigraphy. AB - In order to assess the value of exercise thallium scintigraphy for the detection and prognosis of graft coronary artery disease, 50 heart transplant patients (mean age 46.7 +/- 11.5 years) were studied within 48 h of their scheduled yearly coronary angiography and subsequently followed up for a mean of 13 +/- 3 months. Angiography revealed normal coronary arteries in 35 patients, and coronary artery disease in 15 (two with type A lesions, seven with type B lesions and six with both). Seven patients had one or more stenoses > or = 50%. Exercise thallium scintigraphy was negative in all patients with normal coronary arteries (100% specificity), and abnormal in 10 of 15 patients with coronary artery disease (67% sensitivity). Fixed defects were seen in six cases, transient defects in two and both in two; the results of the test were abnormal in all seven patients with > or = 50% lesions. During follow-up, none of the patients with a normal exercise thallium scintigraphy experienced any cardiac event; in the group with abnormal results, four cardiac events occurred. Although further studies are needed to confirm these results, exercise thallium scintigraphy seems to be useful in evaluating post-transplant coronary artery disease: it is accurate in detecting the most severe stenoses and provides some prognostic information. PMID- 8449199 TI - Pericardial clot after open heart surgery: its specific localization and haemodynamics. AB - Transoesophageal echocardiography disclosed a localized pericardial blood clot compressing the right atrium (RA) and/or right ventricle (RV) in 15 patients suffering from low cardiac output failure soon after open-heart surgery. The left ventricular end-diastolic diameter was small (38.4 +/- 10.1 mm) and its fractional shortening normal (34.9 +/- 10.2%). These findings suggested cardiac tamponade as a result of pericardial clot. However, the 'y' trough of the RA pressure tracing was prominent, which is not characteristic of typical cardiac tamponade, but rather of constrictive pericarditis. This implies therefore that the pathophysiology of cardiac tamponade by pericardial clot differs from that of tamponade by fluid. Emergency open-chest removal of the pericardial clot was performed in seven patients, with good results. Pericardial clot produces low cardiac output soon after open-heart surgery, but its location is specific and its haemodynamics are not characteristic of cardiac tamponade. PMID- 8449200 TI - Repeat percutaneous coronary angioplasty; clinical and angiographic follow-up in patients with stable or unstable angina pectoris. AB - This study analyses the immediate outcome and the risk of recurrent restenosis in patients who, at the time of repeat coronary angioplasty for a first restenosis, had unstable (n = 50), 19%) or stable (n = 218, 81%) angina. Successful angioplasty was accomplished in 250 (93%) patients, 222 (89%) of whom had follow up angiography. Mean time from initial to repeat angioplasty was shorter (P = 0.0002) and angiographic evidence of thrombus was commoner (P = 0.0001) in the unstable group. Major complications (coronary artery bypass grafting or myocardial infarction) were more frequent (P < 0.01) in the unstable group (6% vs 0.5%); no procedure-related deaths occurred. The angiographic rate of restenosis was significantly higher in the unstable group (61% vs 43%, P < 0.05). Despite this high rate of recurrent restenosis, most of the patients in both groups were either asymptomatic or had atypical chest pain at follow-up. Repeat coronary angioplasty, in patients with unstable angina, has a high primary success rate but a higher risk of acute complications than in patients with stable angina. The angiographic rate of restenosis was significantly higher in unstable than in stable patients; however, the clinical status of most patients was improved at follow-up. PMID- 8449201 TI - Maximal functional capacity in patients with endomyocardial fibrosis. AB - We evaluated objectively the cardiocirculatory dysfunction of patients with EMF, and related the functional class (FC-NYHA) to the data obtained by analysis of maximal functional capacity. We studied 55 subjects, divided into three groups: group 1 (G1) 21 (38.1%) normal persons, group 2 (G2) seven (12.7%) patients with EMF who were in FC I or II, and group 3 (G3) 27 (49%) patients in FC III or IV. Maximal oxygen consumption (VO2max) and O2 pulse index (PO2max) were obtained using a Beckman computerized gas analyser. The mean values were significantly different among the three groups. We conclude that the greater the clinical impairment, the greater the alterations that occur in the indices of cardiac function. PMID- 8449202 TI - The influence of intravenous magnesium sulphate on the occurrence of atrial fibrillation after coronary artery by-pass operation. AB - To examine the influence of magnesium (Mg) on hypomagnesaemia and atrial fibrillation (AF) following coronary artery by-pass surgery, 140 consecutive patients were randomized to receive 70 mmol of magnesium sulphate intravenously (n = 69) or placebo (n = 71). Serum magnesium concentrations fell to 0.77 +/- 0.10 mmol.l-1 in the control group but rose to 1.09 +/- 0.17 mmol.l-1 in the Mg group (P < 0.001). The incidence of AF was 29% in the Mg group and 26% in the placebo group (NS). The AF patients were older, more of them had had prior AF episodes, their sinus rates (SR) were slower (78 +/- 10 vs 86 +/- 12 beats.min-1; P < 0.01) and serum Mg concentrations higher (0.89 +/- 0.21 vs 0.80 +/- 0.11 mmol.l-1; P < 0.05). The incidence of AF was 43% in the highest quartile of serum Mg and 23% among the rest (P = 0.056). In patients experiencing AF during the first three post-operative days, serum Mg concentrations were higher and SR slower on each day compared with non-AF patients. SR increased post-operatively less with high Mg levels (P = 0.044). In the Mg group, serum Mg and SR were the only independent predictors of AF. In conclusion, the incidence of post-operative AF is not decreased with magnesium. High Mg levels are likely to provoke AF probably by mechanisms that modify SR. PMID- 8449203 TI - Effects of early use of captopril on haemodynamics and short-term ventricular remodelling in acute anterior myocardial infarction. AB - To determine whether ventricular short-term enlargement following acute myocardial infarction is related to increased left filling pressures and whether early treatment with captopril alters this process we studied 68 patients with a first acute myocardial infarction. Forty patients with a pulmonary capillary pressure equal or above 17 mmHg were randomized to treatment with conventional therapy plus captopril (n 20) or placebo (n 20), in a double blind fashion. The remaining 28 patients (non-dysfunction group) were treated conventionally. During the first 72 h, afterload showed a prompt decrease in the captopril group as compared to placebo. Changes from baseline to 14 days in end-diastolic and end systolic left ventricular volume indexes determined by radionuclide ventriculography were: non-dysfunction, 85.6 (+/- 21) vs 88 (+/- 20) and 44 (+/- 17) vs 44 (+/- 17) ml.m-2; captopril (n 20), 96.6 (+/- 18) vs 99 (+/- 19) and 66 (+/- 22) vs 65 (+/- 22) ml.m-2; placebo (n 20), 96 (+/- 25) vs 113 (+/- 19) (P < 0.001) and 63 (+/- 18) vs 74 (+/- 22) ml.m-2 (P < 0.01). This study indicates that short-term ventricular enlargement is related to the degree of ventricular dysfunction and that captopril may improve this process. PMID- 8449204 TI - Cibenzoline transforms random re-entry into ordered re-entry in the atria. AB - The goal of this study was to test the hypothesis that class I drugs modify the electrophysiological substrate of atrial fibrillation. The effects of a single intravenous dose (1.4 +/- 0.3 mg.kg-1) of the new class I drug, cibenzoline, were studied in 20 patients with spontaneous (n = 11) or induced (n = 9) atrial fibrillation, during an electrophysiological study. In one additional patient with chronic atrial fibrillation, the effects of a single intravenous dose of 2 mg.kg-1 of cibenzoline were studied intra-operatively before undergoing a 'corridor' operation. High resolution epicardial mapping (248 channels) was used to reconstruct the atrial activation patterns before and after administration of the drug. In 18 out of 20 patients administration of cibenzoline resulted in conversion of atrial fibrillation into regular monomorphic atrial tachycardia. In these 18 patients, the mean atrial cycle length was prolonged from 147 +/- 34 ms during atrial fibrillation to 302 +/- 34 ms after cibenzoline (P < 0.001). In eight out of the 18 patients, spontaneous (n = 3) or pacing induced (n = 5) conversion into sinus rhythm was observed after administration of the drug. In the patient undergoing the 'corridor' operation, epicardial mapping of both atria showed that the multiple wavelets present during atrial fibrillation fused into a single broad wavefront circulating counterclockwise around the caval veins after cibenzoline. In conclusion, cibenzoline transforms random re-entry into ordered re-entry in the atria. This effect seems related to the depression of conduction produced by the drug. PMID- 8449205 TI - Clinical and neurohumoral response of patients with severe congestive heart failure treated with two different captopril dosages. AB - Although angiotensin converting enzyme inhibitor therapy is an established approach in the treatment of chronic heart failure, the required dosage remains unclear. This open 6 month study investigated the influence of different captopril dosages on the clinical course and neurohumoral activity of patients with severe heart failure (left ventricular ejection fraction < or = 20%). Eighty five patients in New York Heart Association class II-IV despite treatment with digitalis, diuretics, and captopril (mean dose +/- SEM 28 +/- 2 mg.day-1 at baseline) for > or = 3 months received either 'low dose' captopril (< 75 mg.day 1, mean 32 +/- 2 mg.day-1; n = 46) or 'high dose' captopril (> or = 75 mg.day-1, mean 99 +/- 4 mg.day-1; n = 39) during the follow-up period. Both groups were comparable in clinical, haemodynamic and neurohumoral parameters at baseline. Functional state improved significantly only in the high dose group (P < 0.0001). Of 31 low dose and 20 high dose patients considered as heart transplantation candidates at baseline, 21 low dose and only six high dose patients remained on the waiting list (P < 0.0001). In patients in the low dose group, eight deaths were observed (P < 0.001). Seven patients remained on low dose captopril due to adverse effects. The initially elevated plasma levels of aldosterone and atrial natriuretic peptide decreased significantly only in high dose patients (P < 0.01). Renin increased significantly in both groups. These observations underline the necessity of suppressing neurohumoral overactivation with adequate doses of captopril reflected by sequential humoral plasma determination. PMID- 8449206 TI - Negative inotropy of lidocaine: possible biochemical mechanisms. AB - Previous studies have shown that lidocaine has a negative inotropic effect on the myocardium. This effect could be mediated by a decrease in O2 supply and/or utilization, or abnormalities in intracellular Ca2+ handling by the myocardium. To investigate which of these mechanisms are involved we studied nine open-chest anaesthetized pigs, which received an infusion of lidocaine (4-16 mg.min-1) in the left anterior descending coronary artery (LADCA), sufficient to induce a severe depression of the regional myocardial function. Biopsies for high energy phosphate levels were obtained from both the LADCA and control regions before and during the infusion. After measurements at peak lidocaine dose, the hearts were rapidly excised for harvesting of LADCA, and control region sarcoplasmic reticulum (SR) vesicles for in vitro measurements of Ca2+ uptake rate. During lidocaine infusion, coronary blood flow increased (23%), while ATP, Ca2+ uptake by the SR and percentage segment length shortening decreased by 20%, 19% and 30% respectively. However, O2 consumption in the LADCA region did not differ before or during lidocaine infusion (102 +/- 20 and 104 +/- 29 ml.min-1, respectively). Hence, lidocaine in doses sufficient to depress regional myocardial function does not decrease O2 supply, but decreases the efficiency of oxygen utilization. Although we cannot entirely rule out the possibility that blockade of fast sodium channels is a contributory factor, the observed decrease in the tissue level of ATP and the rate of Ca2+ uptake by the SR may be related to the negative inotropic action of lidocaine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8449207 TI - An abnormal pattern of systolic and diastolic temporal phases and function in severe obesity. PMID- 8449208 TI - Joint meeting of the Deutsche Gesellschaft fur Zellbiologie and the Dutch Society for Cell Biology. Munster, March 28-April 1, 1993. Abstracts. PMID- 8449209 TI - Isolation of an HLA-A2.1 extracted human minor histocompatibility peptide. AB - Purified HLA-A2.1 molecules obtained by affinity chromatography of 6 x 10(10) Epstein Barr virus (EBV)-transformed B lymphocytes were used in an attempt to isolate the human HLA-A2.1-restricted minor histocompatibility (H) peptides H-Y and HA-2. Fraction 18 of the high-performance liquid chromatography (HPLC) separated HLA-A2.1 peptide pool was found to contain the natural HA-2 peptide. An HA-2-specific, HLA-A2.1-restricted cytotoxic T lymphocyte clone lysed HLA-A2.1+ HA-2- EBV-transformed B lymphocyte cell lines reproducibly and in a concentration dependent fashion in the presence of fraction 18, but not in the presence of other HPLC fractions. By contrast, H-Y sensitizing activity was not found in any fraction. Amino acid sequencing of peptide fraction 18 revealed a mixture of peptides with maximal length of nine amino acids, in which the presence of Leu at positions 2 and 9 was dominant. Surprisingly, the HA-2 peptide could not be mimicked by any of the peptide mixtures synthesized according to the amino acid sequences found in fraction 18. Our failure to obtain the actual amino acid sequence of the human minor H peptide HA-2 from a peptide pool with the established pattern for binding to HLA-A2.1 may indicate that this CTL defined minor H peptide does not represent an abundant HLA-A2.1 binding peptide. PMID- 8449210 TI - Diversity of immunoglobulin kappa light chain gene rearrangements and evidence for somatic mutation in V kappa IV family gene segments in X-linked agammaglobulinemia. AB - X-linked agammaglobulinemia (XLA) is a humoral immunodeficiency disease in man, characterized by an arrest in B lymphocyte differentiation at the precursor B cell stage. The structure of expressed immunoglobulin (Ig) kappa light (L) chain rearrangements of nine B lymphoblastoid cell lines from one XLA patient was investigated by amplification of cDNA by the polymerase chain reaction using 5' V kappa family-specific primers and a 3' kappa constant region primer. Members of all four V kappa gene families were found to be utilized in Ig kappa L chain rearrangements at frequencies that were consistent with random V kappa family usage. There was no preference for usage of any particular kappa joining segment. Additional diversity was generated by deletions and random nucleotide insertions at the site of juxtaposition. Particular V kappa members seemed to be overrepresented in the sample. The observed homology of the V kappa I, V kappa II and V kappa III region sequences, both to each other and to known germ-line V kappa sequence indicated the absence of somatic mutations in the majority of these expressed Ig genes. In contrast of the single-member V kappa IV family four different sequences were found to be expressed. That these sequences were mutated derivatives of a germ-line V kappa IV element was substantiated both by sequence analysis and oligonucleotide hybridization. This finding shows that the mutation process can occur in early stages of B cell development i.e. before H chain class switch has occurred. The presence of these mutations is probably independent of clonal expansion since XLA patients are unable to respond to antigen. We conclude that the differentiation arrest in XLA does not preclude early onset of somatic mutation events in V kappa gene segments. PMID- 8449211 TI - A promoter element of the human serine esterase granzyme B gene controls specific transcription in activated T cells. AB - The human granzyme B gene encodes a serine protease expressed specifically in cytoplasmic granules of cytotoxic T lymphocytes, released upon effector-target cell interaction. Previous studies have shown that granzyme B mRNA was induced in T lymphocytes after antigenic or mitogenic stimulation. To study the regulation of human granzyme B gene expression during lymphocyte activation we analyzed its 5' flanking region using chloramphenicol acetyl transferase (CAT) reporter gene constructs. We show that a 208-bp fragment (-148 to +60) containing an NF-AT (nuclear factor of activated T cells)-binding site promotes CAT expression in phytohemagglutinin-activated T lymphocytes, in immobilized monoclonal anti-CD3 antibody-activated Jurkat T cell line while it is inactive in unstimulated PEER and Jurkat T cells lines or B Epstein-Barr virus-transformed cell lines. PMID- 8449212 TI - Chimeric Fc receptors identify immunoglobulin-binding regions in human Fc gamma RII and Fc epsilon RI. AB - Fc gamma RII and Fc epsilon RI are functionally distinct cell surface receptors for immunoglobulin (Ig); Fc gamma RII binds IgG with low affinity, whereas Fc epsilon RI binds IgE with high affinity, yet they are homologous in structure and sequence having extracellular regions containing two Ig-like domains with 38% amino acid identity. Chimeric receptors derived from human Fc gamma RII and Fc epsilon RI were produced by exchanging homologous regions of the two receptors to define binding region(s) for IgG in Fc gamma RII and IgE in Fc epsilon RI. Firstly, a chimeric form of the Fc epsilon RI alpha chain was produced by replacing the transmembrane region and cytoplasmic tail with that of Fc gamma RII. This mutant alpha chain could be expressed on the cell surface independently of associated beta and gamma subunits, and retained high-affinity IgE binding, indicating that the extracellular region of the Fc epsilon RI alpha chain is sufficient for high-affinity IgE binding. Secondly, to identify the role of the individual domains in Fc binding of both Fc gamma RII and Fc epsilon RI, chimeric receptors were generated by exchanging the first extracellular domains between Fc gamma RII and the alpha chain mutant and used to demonstrate that the second extracellular domain of both receptors contains region(s) directly involved in Ig binding. Additional chimeric receptors were constructed to localize the Ig interactive regions in domain two of Fc gamma RII and Fc epsilon RI; these identified a single region of IgG binding in Fc gamma RII located between residues Ser136 to Val169, and at least three independent IgE binding regions in the Fc epsilon RI alpha chain, between residues Trp87 to Lys128, Tyr129 to Asp145, and Ser146 to Val169. PMID- 8449213 TI - Expression and function of HLA-B27 in lipid-linked form: implications for cytotoxic T lymphocyte-induced apoptosis signal transduction. AB - Major histocompatibility complex (MHC) class I antigen-restricted cytotoxic T lymphocytes (CTL) kill their target cells not only by inducing irreversible membrane damage but also by triggering a programmed suicide cascade (apoptosis) in target cells. Recent evidence suggests that MHC class I antigens are involved in apoptosis signal transduction in T cells. Therefore, it is possible that MHC class I antigens are also responsible for CTL-induced signal transduction in target cells leading to apoptosis. To test this hypothesis, we have expressed HLA B27 in Chinese hamster ovary (CHO) cells in a phosphatidyl inositol (PI) anchored form. The expressed Pl-anchored HLA-B27 (PI-B27), a 42-kDa molecule which can be cleaved off the cell surface by PI-specific phospholipase C, can function as an MHC restriction and antigen presentation element for specific CTL. Furthermore, PI-B27 transfectant CHO cells undergo rapid DNA fragmentation when pulsed with the appropriate peptide and treated with specific CTL, suggesting that the cytoplasmic and transmembrane domains of the heavy chain of class I MHC molecules are not required in CTL-induced apoptosis signal transduction in target cells. PMID- 8449214 TI - Antisense oligonucleotides to interleukin-4 regulate IgE and IgG2a production by spleen cells from Nippostrongylus brasiliensis-infected rats. AB - Interleukin-4 (IL-4) plays a key role in the regulation of immunoglobulin production. In the present study, we examined the role of IL-4 in the production of IgE and IgG2a by spleen cells from Nippostrongylus brasiliensis-infected rats using the antisense oligonucleotide strategy. Three antisense oligonucleotides (15 and 20 nucleotides) were selected near the ATG initiation codon of the murine IL-4 gene. Significant and reproducible inhibitions of IgE and IgG2a production were observed with the addition of two different oligonucleotides, the most inhibitory being specific for 15 nucleotides corresponding to the downstream AUG sequence oligodeoxynucleotide (ODN-1), while the corresponding sense sequence had no effect. The inhibition was directly related to the ODN-1 concentration on IgE response, and IgG2a production was more sensitive to the inhibitory effect of ODN 1 than the IgE response. Our results suggest that the ODN-1 effect is rather specific for the IL-4 gene since the production of other cytokines was not modified and the exogenous addition of IL-4 reversed the ODN-1 effect. In contrast to IgE and IgG2a, ODN-1 induced a significant enhancement of IgM synthesis. The use of a phosphorothioate ODN of the same sequence as ODN-1 resulted in a greater inhibitory effect on IgE and IgG2a production. These data indicate that IL-4 contributes to the spontaneous production of IgE and IgG2a, and argue that antisense strategy constitutes a useful tool for the regulation of antibody response. PMID- 8449215 TI - Mercuric chloride down-regulates T cell interferon-gamma production in brown Norway but not in Lewis rats; role of glutathione. AB - Injection of a low dose of mercuric chloride into Brown Norway (BN) rats caused a marked decrease in the concanavalin A (ConA)-induced generation of interferon gamma-producing cells (IFN-gamma pc) in spleen cell cultures prepared 1 h after mercury administration. A second injection 48 h later caused a further diminution of IFN-gamma pc down to 30% of the number generated in splenocyte cultures of phosphate-buffered saline (PBS)-injected controls. Injection of Lewis rats with either one or two doses of HgCl2 revealed no inhibitory effect on splenic IFN gamma production. The presence of the reduced form of glutathione (GSH) in the culture medium was found to be essential in these experiments. In the absence of GSH there was an overall 20-fold reduction of the number of IFN-gamma pc in splenocyte cultures of normal or PBS-injected rats, which was further reduced to a 60- to 70-fold-lower level in cultures of rats exposed to HgCl2. This mercury mediated extra reduction could be fully reversed with an excess (2 mM) of GSH in Lewis but not in BN splenocyte cultures. Since the bivalent Hg2+ ion is known to bind to and inactivate sulfhydryl groups of proteins and low molecular weight thiols, most notably GSH, we investigated a possible role for thiols in IFN-gamma production. It was found that the generation of IFN-gamma pc in normal BN and Lewis splenocyte cultures was strongly dependent on GSH or its precursor cysteine in the culture medium. Other thiol compounds were also effective but disulfides were completely inactive. Depletion of intracellular GSH in ConA-stimulated splenocytes by buthionine sulfoximide (BSO), an inhibitor of de novo GSH biosynthesis, strongly inhibited the generation of IFN-gamma pc. The inhibitory effect of BSO was not abolished by the addition of interleukin-2 (IL-2), but was mimicked with antibodies directed to the IL-2 receptor. The data stress the importance of GSH in the enhancement of IL-2-mediated IFN-gamma production and are most consistent with a model in which mercury interferes with T cell IFN gamma production by affecting the intracellular availability of GSH. The strain specific susceptibility to mercury-mediated inhibition of IFN-gamma production is discussed. PMID- 8449216 TI - Monoclonal antibodies to the integrin alpha-4 subunit inhibit the murine contact hypersensitivity response. AB - Lymphocyte-endothelial cell recognition is an active multistep process central to the pathophysiology of inflammation. In vitro models of lymphocyte adhesion predict that the beta 1 integrin very late antigen-4 (VLA-4), an activation dependent adhesion receptor, can mediate the firm sustained attachment required for the extravasation of memory lymphocytes. We have used murine contact hypersensitivity as an in vivo model in which to evaluate the role of alpha-4 integrins in an evolving inflammatory response. We demonstrate that the intravenous administration of 75 micrograms of the anti-alpha-4 specific monoclonal antibodies R1-2 or PS/2 4-6 h prior to challenge significantly inhibits the efferent response of 2,4 dinitrofluorobenzene, or oxazolone sensitized mice. The disease-modifying effect of anti-alpha 4 treatment was evident as a 50-60% reduction in the ear swelling response. By histological analysis treated animals scored lower for edema, number of epidermal lesions and degree of leukocyte infiltration. Antibody-treated animals have elevated numbers of circulating mononuclear leukocytes present in the same relative ratio as untreated control animals, suggesting that the inhibitory effect was not due to antibody-dependent cellular depletion of effector lymphocytes. These data are consistent with a central role for VLA-4 in the pathophysiologic process of inflammation. PMID- 8449217 TI - Dissociation of natural killer and lymphocyte-activated killer cell lytic activities in human CD3- large granular lymphocytes. AB - CD3- large granular lymphocytes (LGL) are known to display natural killer cell (NK) activity without prior sensitization or restriction by major histocompatibility antigens. Upon short-term exposure to interleukin-2, NK cells were shown to acquire lymphocyte-activated killer cell (LAK) activity. The aim of this study was to analyze the characteristics of these lytic activities. Our data indicated that both NK and LAK activities were Ca2+ dependent; however, they could be dissociated by a Ca2+ channel blocker or a Ca2+ channel competitor agent. Moreover, NK activity was associated with granule exocytosis of lytic proteins spontaneously present in CD3- LGL, the most likely candidate being the pore-forming protein perforin. By contrast, LAK activity was found to be dependent on de novo protein synthesis and distinct from granule exocytosis. Our results strongly suggest that NK and LAK activities could be defined as two distinct pathways involving different lytic mediators. PMID- 8449218 TI - Treatment with anti-CR3 antibodies ED7 and ED8 suppresses experimental allergic encephalomyelitis in Lewis rats. AB - Experimental allergic encephalomyelitis (EAE) is an inflammatory disease of the central nervous system (CNS). Among the leukocytes which infiltrate the CNS during EAE, numerous macrophages are present. These macrophages are thought to play a crucial role in the generation of tissue damage and attendant neurological deficits. The mechanism by which the macrophages migrate across the blood-brain barrier is not yet clear. Membrane proteins involved in macrophage adherence to the endothelium include the CD11b/CD18 integrin, also known as the type 3 complement receptor (CR3). In this study we show that two monoclonal antibodies (mAb) ED7 and ED8 are directed against rat CR3. In addition, these mAb reduce recruitment of myelomonocytic cells towards thioglycollate induced peritonitis by 15-33%. This indicates that both ED7 and ED8 interfere with an epitope on CR3, which is involved in recruitment of phagocytes towards inflammatory lesions. Intravenous injection of ED7 and ED8 suppressed clinical signs of EAE. MRC OX-42, which also recognizes CR3, did not reduce thioglycollate-induced phagocyte recruitment into the peritoneum, and had no effect on EAE. These findings suggest that CR3 plays a role in the recruitment of macrophages towards the inflamed CNS of EAE animals, and confirm the role of macrophages in the generation of clinical signs of EAE. Involvement of CR3 in other phagocyte immune functions during EAE is discussed. PMID- 8449219 TI - The murine T cell line CT6 provides a novel bioassay for interleukin-7. AB - Like interleukin (IL)-2 and IL-4, IL-7 can act as a growth factor for activated T lymphocytes. Upon screening a panel of growth factor-dependent T cell lines, we found that only the cell line CT6 responded to IL-7, indeed as vigorously as to IL-2. Obviously, these findings challenge the validity of previous results on IL 2 production obtained using the CT6 cell line. However, they also demonstrate a novel and sensitive system for the bioassay of IL-7. The ability of the surveyed T cell lines to proliferate to IL-7 corresponded with the expression of IL-7 receptors (IL-7R) on the cell surface. The murine IL-7R on CT6 was shown to bind IL-7 with dual affinity and was visualized as an affinity cross-linked complex of 93 kDa. This IL-7R appears similar to that seen on murine splenic T cells and on 70Z/3, the pre-B cell line from which the murine IL-7R was cloned. PMID- 8449220 TI - Chicken B cells adhere to the CS-1 site of fibronectin throughout their bursal and postbursal development. AB - In chickens, the pre-B cell development takes place in a specialized organ, the bursa of Fabricius. In this study, we show that fibronectin can be detected in the bursa at least from the day 15 of embryonic incubation up to 10 weeks of age after which the bursa starts to involute. During the embryonic incubation, fibronectin localizes mainly in the areas between the follicles and later on also in the border zone between the cortical and medullary parts of the lymphoid follicles. By adhesion studies with synthetic peptides we show that immature bursal B cells bind in a dose-dependent manner to the CS-1 site of the type III connecting segment at the carboxy-terminal end of fibronectin throughout their bursal development. Postbursal B cells from chicken spleen also display a similar preference of binding to the CS-1 site of fibronectin, whereas peripheral blood B lymphocytes bind to the 40-kDa fragment of fibronectin, but do not adhere as strongly to the CS-1 site. Instead, they recognize to some extent also the heparin-binding YEKPGSPPREVVPRPRPGV peptide. The adhesion of the bursal B cells to the CS-1 site can partially be blocked by preincubation of cells with a synthetic CS-1 peptide and also by preincubation with a monoclonal anti fibronectin receptor antibody. In contrast, the RGD motif present in several adhesion-associated stromal molecules did not promote any adherence of bursal lymphocytes. The bursal B cells which adhere to the fibronectin molecule in vitro form only a small fraction of the total number of B cells present in the bursa as only less than 4% of the cells remained bound to the surface coated with fibronectin in the adhesion studies. In conclusion, these results suggest that fibronectin may be involved in the differentiation of pre-B cells in the bursa of Fabricius and also in the adherence of postbursal B cells in the spleen. PMID- 8449221 TI - Soluble T cell receptor-like properties of an HLA-B35-specific monoclonal antibody (TU165). AB - A mouse monoclonal antibody of IgM class (TU165) was produced using Epstein-Barr virus (EBV)-infected mutant cells derived from the human BJAB-B95.8.6 cell line as immunogen. Binding studies with several HLA deletion mutant cell lines indicated that TU165 recognized the HLA-B35 molecule. In a panel of 89 EBV transformed lymphoblastoid cell lines, all HLA-B35+ cells (n = 24) reacted with TU165 while all but two HLA-B35- lines (n = 65) were unreactive (r = 0.95). Surprisingly, peripheral blood lymphocytes of HLA-B35+ donors were unreactive; however, strong enhancement of TU165 recognition was observed with B cells of one of these individuals after transformation with EBV (B95.8 strain). Transfection of both HLA-B35 and human beta 2-microglobulin genomic DNA into mouse P815 cells led to high expression of HLA-B molecules; yet, expression of the TU165 epitope was not observed. Furthermore, the EBV-negative cell line BJAB as well as the EBV infected (P3HR1 strain) line BJAB-HR1K were only weakly reactive, whereas the BJAB-B95.8 cell line was strongly positive. These results indicate that EBV encoded or -controlled peptide(s) must be bound by HLA-B35 antigens to create the epitope which allows efficient binding of TU165. PMID- 8449222 TI - T cell clones specific for p21 ras-derived peptides: characterization of their fine specificity and HLA restriction. AB - Peptides corresponding to the mutated regions of the oncoprotein p21 ras are immunogenic and capable of eliciting HLA class II-restricted T cell responses. Here we report studies on the fine specificity of four T lymphocyte clones (TLC) from a single donor, using various truncated peptides derived from the residues 6 19 of p21 ras and a panel of well-characterized HLA homozygous cells as antigen presenting cells. Putative minimum peptides of nine or ten amino acids could be defined for each TLC. Two of the TLC recognized peptides presented by DR2, and the two others recognized peptides presented by DQ6. Some notable differences in the requirement for certain amino acids were seen between the DR- and DQ restricted TLC. Thus, Ser at residue 17 was required for stimulation of the DQ6 but not the DR2-restricted TLC. Val at residue 8 was essential for stimulation of all TLC, whereas one of the DR2-restricted TLC also required Val at residue 7. Some peptides which were nonstimulatory were still capable of binding to DQ6 molecules in peptide competition experiments. The results may be of importance for potential immunotherapy of cancer where transforming ras oncoproteins are involved. PMID- 8449223 TI - Role of environmental antigens in B cell proliferation in the bursa of Fabricius at neonatal stage. AB - Effect of environment antigens on S phase entry rate of bursa cells was studied by utilizing in vivo incorporation of bromodeoxyuridine (BrdUrd). S phase entry rate of bursa cells in chick embryo was determined to be 6.4%/h, this rate increased to 10.0%/h at neonatal stage and decreased to 6.4%/h 6 weeks after hatching. Evidence is presented that isolation of the bursa from the gut before hatching suppressed S phase entry rate of bursa cells after hatching, whereas S phase entry rates of thymocytes were not affected. On tissue sections, a decrease of BrdUrd+ cells was observed in medullary areas of the isolated bursa. It is proposed that in situ stimulation of bursa cells by environmental antigens to the bursa accelerates S phase entry rates, and that medullary areas are the major sites for antigen-driven B cell proliferation after hatching. PMID- 8449224 TI - Antigen-specific therapy of experimental myasthenia gravis with acetylcholine receptor-gelonin conjugates in vivo. AB - Rats suffering from experimental autoimmune myasthenia gravis (EAMG) induced by previous immunization with foreign acetylcholine receptor (AChR) were treated with AChR-toxin conjugates using the plant toxin gelonin. This led to a marked improvement of clinical symptoms as well as a significant increase in functional AChR compared to untreated rats with EAMG as determined 6 to 10 weeks later. No therapeutic effect was observed after treatment with gelonin or AChR alone. The immune response to irrelevant control antigens was not altered by this treatment. PMID- 8449225 TI - Effects of K+ channel openers on ischemic dysfunction and metabolic disturbance in isolated perfused rat heart. AB - The effects of two structurally different K+ channel openers, KRN2391 and cromakalim, on cardiac mechanisms during ischemia and reperfusion were studied in isolated perfused rat hearts. Isolated buffer-perfused rat hearts pretreated with KRN2391, cromakalim and vehicle were subjected to 25 min of ischemia followed by 30 min of reperfusion. Before ischemia, KRN2391 (1-10 microM) and cromakalim (1 10 microM) increased coronary flow, but did not modify cardiac function or biochemical parameters (adenine nucleotides, energy charge potential: ECP, lactate). During ischemia, KRN2391 (3, 10 microM) and cromakalim (10 microM) significantly accelerated the reduction in cardiac function and attenuated the decreased levels of ATP and ECP, but did not change the lactate content. After 30 min of reperfusion, pretreatment with KRN2391 and cromakalim resulted in a significant improvement in cardiac function, ischemic contracture and biochemical parameters. Thus, both KRN2391 and cromakalim have beneficial effects on biochemical parameters during ischemia and reperfusion, effects which may be related to cardiodepression during ischemia. PMID- 8449226 TI - 5-HT2 receptors augment cholinergic nerve-mediated contraction of rat bronchi. AB - 5-Hydroxytryptamine (5-HT) potentiated contractions of isolated rat bronchi evoked by electrical field stimulation (EFS). The degree of potentiation caused by 5-HT was dependent upon concentration of the amine present in the tissue bath. The effects of antagonists selective for different subtypes of the 5-HT receptor on potentiation of EFS-induced contractions by 5-HT were examined. Propranolol, a nonselective beta-adrenoceptor antagonist which can act as a 5-HT1 receptor antagonist, did not inhibit the effect of 5-HT on EFS-induced contractile responses. Similarly, 5-HT3 receptor antagonism with MDL 72222 or ICS 205-930, did not inhibit the facilitatory effects of 5-HT. However, ketanserin, mianserin and spiperone, 5-HT2 receptor antagonists, abolished the effects of 5-HT on EFS induced responses. These latter results suggested that the potentiation was dependent upon activation of 5-HT2 receptors thus additional experiments were conducted using the 5-HT2 receptor agonist, alpha-methyl-5-hydroxytryptamine (alpha-Me-5-HT). alpha-Me-5-HT caused a concentration-dependent potentiation of EFS-induced contractile responses comparable to that observed with 5-HT. Concentrations of alpha-Me-5-HT that significantly potentiated EFS-induced contraction were essentially without effect on airway smooth muscle contraction elicited by exogenous acetylcholine. These results are consistent with a role for 5-HT2 receptor activation in mediating the facilitatory effects of 5-HT on cholinergic nerve-mediated responses in airways. PMID- 8449227 TI - Activation of 5-HT2 receptors facilitates depolarization of neocortical neurons by N-methyl-D-aspartate. AB - The interaction between serotonin and excitatory amino acid agonists at rat neocortical neurons was investigated using the grease-gap recording method. Depolarization evoked by 50 microM N-methyl-D-aspartate was dose dependently facilitated by serotonin (5-HT) (1 to 100 microM) giving a bell-shaped dose response curve with maximum enhancement at 30 microM. In contrast, quisqualate and kainate depolarizations were not enhanced. Subnanomolar concentrations of methysergide, ritanserin and spiperone, but not ICS 205-930, attenuated the 5-HT enhancement, compatible with 5-HT2, but not 5-HT1 or 5-HT3 receptor subtype involvement. Enhancement was observed with 5-HT2 receptor agonists, whereas 5-HT1 receptor subtype agonists had either no effect (1B and 1C) or reduced (1A) the N methyl-D-aspartate depolarization. Scopolamine and prazosin reduced the N-methyl D-aspartate depolarization and blocked facilitation induced by carbachol and phenylephrine, but not that due to 5-HT. Tetrodotoxin reduced the N-methyl-D aspartate depolarization, but the facilitation by 5-HT persisted. Activators of protein kinase C (phorbol diacetate and 1-oleoyl-2-acetyl-sn-glycerol) did not mimic the serotonin facilitation. We conclude that serotonin enhances N-methyl-D aspartate depolarization of rat cortical neurons through activation of 5-HT2 receptors, however the cellular mechanism underlying the facilitation remains to be established. PMID- 8449228 TI - Non-opioid antitussives and methadone differentially influence hippocampal long term potentiation in freely moving rats. AB - Long-term potentiation (LTP) of monosynaptically evoked field potentials (MEFP) in the dentate gyrus of freely moving rats following tetanization of the perforant pathway was investigated after peripheral application of substances which have been shown to influence NMDA receptor-mediated effects (dextromethorphan, methadone) as well as structurally related substances with similar antitussive effects (codeine, normethadone). The noncompetitive NMDA receptor antagonist MK 801 was also tested for comparison. Whereas under control conditions the field e.p.s.p. (excitatory postsynaptic potential) and the population spike of the MEFP were largely uninfluenced by these substances, different effects were seen after the induction of LTP. MK 801 (0.2 mg/kg i.p.) suppressed the induction of LTP of both the field e.p.s.p. and the population spike. Dextromethorphan (40 mg/kg i.p.) also prevented the potentiation of the field e.p.s.p. and the population spike, thus resembling MK 801 in its effect. Codeine (20 mg/kg i.p.), the levorotatory structural analogue of dextromethorphan had no effect. Methadone and normethadone did not influence the potentiation of the field e.p.s.p. or interfere with the induction of potentiation of the population spike but depressed its maintenance. The results obtained with MK 801 confirm those reported by others. Comparison of the effects of dextromethorphan with those of MK 801, suggests that there is a direct interaction with the NMDA receptor-ionophore complex. The effects of methadone and normethadone appear not to be linked to an interaction with opioid receptors, since naloxone did not influence the suppression of LTP caused by methadone. The possibility of interference with the NMDA receptor-ionophore complex is discussed. PMID- 8449229 TI - Effects of gallopamil, a Ca2+ channel blocker in models of ventricular arrhythmia in dogs. AB - The antiarrhythmic effects of gallopamil on adrenaline-, digitalis- and two-stage coronary ligation-induced arrhythmias and on adrenaline-induced triggered arrhythmia were investigated. Gallopamil suppressed adrenaline-induced and adrenaline-induced triggered arrhythmias, and these antiarrhythmic effects of gallopamil were similar to those of verapamil. Gallopamil also showed some antiarrhythmic effect on the 48-h coronary ligation-induced arrhythmia. The plasma concentration of gallopamil which decreased the arrhythmic ratio for adrenaline-induced arrhythmia by 50% (IC50) was 32 ng/ml. These results indicate that gallopamil may be a clinically useful antiarrhythmic drug. PMID- 8449230 TI - ETB receptor antagonist, IRL 1038, selectively inhibits the endothelin-induced endothelium-dependent vascular relaxation. AB - In isolated rat aorta, endothelin-1 induced contractions at lower concentrations than endothelin-3. The contractile effects were augmented by removing the endothelium. In contrast, endothelium-1 and endothelin-3 at similar concentrations induced endothelium-dependent relaxation in norepinephrine stimulated aorta. IRL 1038 ([Cys11,Cys15]endothelin-1(11-21); 3 microM) augmented the contractile effects of endothelins only in the presence of the endothelium. IRL 1038 (0.3-3 microM) inhibited the endothelium-dependent relaxation induced by endothelins but not by carbachol. IRL 1038 itself did not change muscle tension. These results suggest that IRL 1038 is a novel antagonist of the ETB receptor responsible for the release of relaxing factor from the vascular endothelium. PMID- 8449231 TI - Neuropeptide Y and sigma receptor agonists act through a common pathway to stimulate duodenal alkaline secretion in rats. AB - Neuropeptide Y (NPY) has been shown to mimic the effects of some sigma receptor agonists in the brain and to possess the same proabsorptive effect as these agonists in the isolated mouse jejunum. The aim of present study was to investigate the effect of NPY on duodenal alkaline secretion in the rat and to define its mode of action. NPY (0.01 to 3 micrograms/kg i.v.) induced a dose related increase in duodenal bicarbonate secretion, the maximal effect being obtained at 1 micrograms/kg. This response was significantly inhibited by the i.v. administration of haloperidol, BMY 14802, devazepide, hexamethonium, tetrodotoxin and by bilateral truncal vagotomy, but not by SCH 23390, sulpiride, prazosin or atropine, whereas i.c.v. devazepide had no effect. This pharmacological profile is identical to that reported for sigma receptor agonists. The results suggest that NPY and sigma ligands act through a common pathway to stimulate duodenal alkaline secretion in the rat. PMID- 8449232 TI - The effect of MR16728, a cetiedil analogue, on acetylcholine release in Torpedo synaptosomes. AB - MR16728, a cetiedil analogue, enhanced acetylcholine (ACh) release (up to 145% of control) from Torpedo synaptosomes when the release was triggered by a Ca2+ ionophore, A23187 or ionomycin, in the presence of 4 mM Ca2+ in the release medium, but inhibited ACh release induced by KCl depolarization of the presynaptic membrane. MR16728 also inhibited Ca(2+)-ATPase activity measured in purified synaptosomal presynaptic membranes. We studied the stimulation by MR16728 as a function of its concentration; the half-maximal effect was reached at the concentration of 13.5 microM. Moreover the stimulation was more pronounced (up to 300%) when a low concentration of Ca2+ (in the 10-micromolar range) was added to the medium. The enhancement of ACh release was also observed in proteoliposomes having incorporated mediatophore, a presynaptic membrane protein, able to release ACh in a Ca(2+)-dependent manner. Thus, mediatophore is a potential presynaptic target for MR16728. PMID- 8449233 TI - Endogenous nitric oxide modulates morphine-induced changes in locomotion and food intake in mice. AB - Opioids increase the dopaminergic turnover in nucleus striatum and nucleus accumbens of mice, causing behavioural changes such as increased locomotion and food intake. We have now shown that L-arginine administration increases morphine induced locomotion and changes in food intake in mice. D-Arginine had no effect, suggesting a stereospecific mechanism. Furthermore NG-nitro-L-arginine methyl ester, a specific inhibitor of nitric oxide synthase, reduced the morphine induced effects. These results suggest that endogenous nitric oxide could play a role in the modulation of dopaminergic effects elicited by morphine. PMID- 8449234 TI - Roles of platelet-activating factor, thromboxane A2, ADP and thrombin in thrombogenesis in the guinea pig. AB - The mediators of photochemically induced thrombosis in the femoral artery of guinea pig were investigated. The femoral artery was occluded by a thrombus about 7 min after the initiation of photochemical reaction between rose bengal and green light. Pretreatment with a specific thromboxane (TX) A2 receptor antagonist, vapiprost, a platelet-activating factor (PAF) antagonist, WEB-2086, and ADP-induced platelet aggregation inhibitor, ticlopidine, prolonged the time to occlusion. Within the range of doses used, platelet aggregation in whole blood, which was induced by U-46619, PAF and ADP ex vivo, was inhibited by vapiprost, WEB-2086 and ticlopidine, respectively. In contrast, argatroban, a thrombin inhibitor, had no effect on the time to occlusion, although the dose of argatroban was sufficient to delay the prothrombin time and the activated partial thromboplastin time and to inhibit thrombin-induced platelet aggregation ex vivo. These results suggest that TXA2, PAF and ADP are involved in photochemically induced thrombosis of the guinea pig femoral artery, although the coagulation cascade does not play an important role. PMID- 8449235 TI - Activity of dihydrothienopyridine S312 enantiomers on L-type Ca2+ channels in isolated rat aorta and cerebral microvessels. AB - The activity of the two enantiomers of the dihydrothienopyridine S312 was characterized in isolated rat aorta and cerebral microvessels. The interaction of S312 with 1,4-dihydropyridine and phenylalkylamine binding sites was also investigated in depolarized rat cerebral microvessels and in membranes from rat ileum. Both S-(+)-S312 and R-(-)-S312 dose dependently inhibited KCl-evoked contraction of the rat aorta, with IC50 values of 0.14 (0.13-0.16) and 2.98 (2.67 3.33) nM, respectively. When the aorta was preincubated with S-(+)-S312 in a depolarizing medium, the inhibitory effect was significantly increased, but this increased inhibition was not reversed by incubation in physiological medium. The effect of R-(-)-S312 was not affected by preincubation in a depolarizing medium. In rat cerebral microvessels, S-(+)-S312 inhibited the KCl-induced contraction and KCl-stimulated Ca2+ influx with similar potency. [3H](+)-PN 200-110 specific binding was competitively displaced by the two enantiomers in depolarized cerebral microvessels. The calculated Ki values were 0.12 nM for S-(+)-S312 and 2.4 nM for R-(-)-S312. Only 20% of [3H]D888 specific binding in rat ileum membranes was displaced by S-(+)-S312. The dissociation rate of [3H]D888 was markedly decreased by S-(+)-S312, and this allosteric interaction was significantly more marked than with nitrendipine. It is concluded that the dihydrothienopyridine S312 could interact with Ca2+ channels in a manner different to that of genuine dihydropyridines. PMID- 8449236 TI - Correlation between potentiation of neurogenic twitch contraction and benzomorphan sigma receptor binding potency in the mouse vas deferens. AB - The effects of sigma receptor ligands on the neurogenic twitch contraction in the ddY mouse vas deferens were studied. In functional studies, (+)-N allylnormetazocine ((+)-SKF-10,047) and (+)-3-(3-hydroxyphenyl)-N-(1 propyl)piperidine ((+)-3-PPP) potentiated neurogenic twitch contractions in a concentration-dependent manner. The potentiation by each (+) enantiomer was significantly more potent than that by the respective (-) enantiomer. In addition, haloperidol and (+/-)-pentazocine also potentiated neurogenic twitch contractions. The order of potentiating ability was: haloperidol > (+/-) pentazocine > (+)-3-PPP > (-)-3-PPP > (+)-SKF-10,047 > (-)-SKF-10,047. In contrast, other sigma receptor ligands, 1,3-di(2-tolyl)guanidine (DTG) and rimcazole, suppressed this twitch contraction. In addition, rimcazole significantly antagonized the (+)-SKF-10,047-induced potentiation at concentrations which did not affect contractions per se. Furthermore, binding studies showed that the kinetic parameters and the inhibitory potencies of sigma receptor ligands for the binding of [3H](+)-SKF-10,047 in the mouse vas deferens were similar to those in the guinea pig brain. The order of potency of sigma receptor ligands to potentiate the neurogenic twitch contraction in the mouse vas deferens was significantly correlated with the potency to inhibit [3H](+)-SKF 10,047 binding in both mouse vas deferens and guinea pig brain. These results indicate that sigma receptor ligands regulate the neurogenic twitch contraction, which is mediated by rimcazole-sensitive benzomorphan-type sigma receptors. PMID- 8449237 TI - In vivo characterization of a phosphoramidon-sensitive endothelin-converting enzyme in the rat. AB - Experiments were conducted to characterize the nature of a phosphoramidon sensitive endothelin-converting enzyme in vivo by evaluating the pressor response to a bolus intravenous (i.v.) injection of endothelin family peptides following administration of phosphoramidon in anesthetized Sprague-Dawley rats. Phosphoramidon given i.v. at 10 mg/kg completely prevented the pressor response to human big endothelin-1-(1-38) (big ET-1). The EC50 for phosphoramidon was determined to be in the range of 1 to 3 mg/kg. The pressor response to big ET-1 60 min after phosphoramidon injection was attenuated by roughly 60% indicating a long inhibitory half-life. Very high doses of big ET-1 (> 20 mg/kg) were capable of over-riding the effect of phosphoramidon and produced characteristic pressor responses suggesting that the inhibition by phosphoramidon can be considered competitive in nature. Human big endothelin-3-(1-41) (big ET-3) produced significant increases in arterial pressure although with less potency and efficacy compared to big ET-1. The pressor response to big ET-3 was also inhibited by phosphoramidon. Phosphoramidon does not act indirectly by interfering with ET-1 receptor-mediated actions since the inhibitor has no effect on the in vivo pressor response to ET-1 and does not antagonize [125I]ET-1 receptor binding or constrictor responses in vitro. These results are consistent with the idea that a phosphoramidon-sensitive endothelin-converting enzyme is capable of cleaving both big ET-1 and big ET-3 to the active peptides in the rat. PMID- 8449238 TI - Pre-contraction with histamine and U46619 unmasks a 5-HT1-like receptor in rabbit renal artery. AB - Rabbit renal arteries were virtually unresponsive to 5-hydroxytryptamine (5-HT) and 5-carboxamidotryptamine (5-CT) under control conditions (including the presence of ketanserin 10(-6) M). However, both agents produced prominent contractions over the range 10(-9)-10(-5) M in tissues pre-contracted with threshold concentrations of either histamine or U46619. These responses were considered to be mediated by activation of 5-HT1-like receptors based on the potency order 5-CT > or = 5-HT and the sensitivity of agonist responses to antagonism by methiothepin (10(-7) M). Pre-contraction with different types of vasoconstrictor can therefore unmask functional 5-HT1-like receptors in rabbit renal artery. PMID- 8449239 TI - Inotropic actions of BDF 9148 and DPI 201-106 and their enantiomers in guinea pig, rat and human atria. AB - The positive inotropic effects of the sodium channel modulators, DPI 201-106 and BDF 9148, were tested in atrial preparations from guinea-pig, rat and man. In rat, the racemate and S enantiomer of both DPI 201-106 and BDF 9148 displayed the same efficacy as did increased extracellular Ca2+, but in guinea-pig and man, the efficacy varied between 60 and 90% of the maximum Ca2+ response. In all three species, BDF 9148 was significantly more potent than DPI 201-106 by approximately one order of magnitude. The same was evident for the S enantiomers. The R enantiomers did not inhibit the effects of the S enantiomers. We have shown pronounced differences in the efficacy and potency of the enantiomers of DPI 201 206 and BDF 9148, which may be useful for future radioligand binding studies. PMID- 8449240 TI - A role of prostaglandin in the secretion of inhibin and oestradiol-17 beta in equine chorionic gonadotrophin-primed rats. AB - The role of prostaglandins in the secretion of inhibin and oestradiol-17 beta was examined in immature female rats treated with equine chorionic gonadotrophin. Administration of prostaglandin (PG) F2 alpha to animals whose serum and ovarian levels of inhibin and oestradiol-17 beta had been suppressed by indomethacin given 24 h after equine chorionic gonadotrophin prevented the inhibition or restored the levels to normal. Initiation of PGF2 alpha replacement immediately after treatment with indomethacin was more effective. The results are consistent with the hypothesis that PGs play a regulatory role in the synthesis and secretion of inhibin and oestradiol-17 beta by the rat ovary. PMID- 8449241 TI - Caramiphen, iodocaramiphen and nitrocaramiphen are potent, competitive, muscarinic M1 receptor-selective agents. AB - Caramiphen, iodocaramiphen and nitrocaramiphen were examined for affinity at the muscarinic M1, M2 and M3 receptor subtypes in radioligand binding assays. Caramiphen binds with high affinity at the M1 site labeled by [3H]pirenzepine in rat cortex (Ki = 1.2 nM) and displays a 27-fold greater preference for the M1 than the M2 site labeled by [3H](-)-quinuclidinyl benzilate in rat heart, and a 6 fold greater preference for the M1 than the M3 site labeled by [3H]N methylscopolamine in rat submaxillary gland. Iodocaramiphen binds with high affinity (Ki = 2.1 nM) and selectivity (59-fold) for the M1 vs. M2 subtype, and is 4-fold more selective for the M1 vs. M3 site. Nitrocaramiphen binds with high affinity for M1 sites (Ki = 5.5 nM) and with a 71-fold selectivity over M2, and a 10-fold selectivity for the M1 over the M3 subtype. All three compounds interacted with the M1 binding site in a competitive manner. Nitrocaramiphen and iodocaramiphen are as potent and showed a comparable selectivity for binding to the M1 over the M2 site than the prototypical agent pirenzepine (M1; Ki = 5.2 nM, 51-fold selectivity). Additionally, nitrocaramiphen demonstrates at least a 10 fold selectivity for the M1 over the M3 site. These ester-type antimuscarinics may be better ligands for the study of M1 receptors in brain than the hydrophilic agent pirenzepine. PMID- 8449243 TI - [Initial characterization of a new miniature animal model in the rat: studies on anatomy, pituitary hormones and GH mRNA in miniature rat Ishikawa]. AB - Miniature rat Ishikawa (MRI) is an experimental model for pituitary miniaturism with an autosomal recessive mode of inheritance. This paper reports the discovery and initial characterization of a new mutant rat. The mutation arose spontaneously in a breeding colony of Wistar rats at the Ishikawa Animal Laboratory (Saitama). Body growth in MRI was retarded in 56% and 71% of normal control rats for males and females, respectively. In immunohistochemical studies for anterior pituitary sections, GH secreting cells were reduced in the amounts and the intensity of stain in MRI compared with normal control rats. There was no detectable difference in the amounts or distribution of LH, FSH, PRL, TSH and ACTH between MRI and normal control rats. MRI showed a selective reduction in pituitary GH contents and in response to human GRH. Pituitary GH contents were approximately 31% of normal in males and 45% in females. Pituitary TSH contents and serum TSH levels were within the normal range in MRI. Total T3 and T4 levels were also within the normal range in MRI. Pituitary total mRNA extracts revealed that GH message in male MRI was reduced in 53% of normal control rats, and that fragment size of GH mRNA was within the normal range. The immunohistochemical findings, supported by a reduced GH content in pituitary extracts and low GH response to GRH, were compatible with a deficiency of GH caused by a reduced expression of pituitary GH mRNA. MRI, which showed a selective pituitary GH deficiency, may provide a useful new model for studying the endocrinological aspects of the growth. PMID- 8449242 TI - [Androgen-dependent tumor]. AB - Androgen receptor is necessary for the proliferation of androgen-dependent tumors including human prostatic cancer and murine androgen-sensitive tumors. However, androgen-independent tumor containing functional androgen receptor was observed in CS 2 cells, which is a subline of androgen-dependent mouse tumor (SC 115). CS 2 showed a new expression of hst-1, the product of which is a family of FGF. CS 2 secreted a growth factor which promotes growth of CS 2 and original SC 115 in an autocrine and paracrine manner. The role of oncogene(s) and suppressor gene(s) on the progression of the tumor is discussed. PMID- 8449244 TI - [A case of familial insulin resistance due to type A insulin receptor disorder]. AB - We report a case of familial insulin resistance due to Type A insulin receptor disorder. The patient, a product of consanguineous marriage, was a 34-year-old man who had had diabetes mellitus since the age of 14 years. He was treated by insulin therapy but became blind due to diabetic retinopathy at the age of 25 years. He was 154 cm tall and weighed 41kg. He had hirsutism and acanthosis nigricans. Laboratory data revealed hyperinsulinemia (140-350 microU/ml), and glucose clamp study showed insulin resistance, i.e. decreased glucose metabolic clearance rate, 20% of normal. Insulin binding was decreased to 10.7-16.6% of normal in erythrocytes, cultured fibroblasts and transformed lymphocytes. Glucagon stimulated C-peptide levels decreased gradually during a 3 year follow up period. Homologous missense mutation from Proline193 to Leucine193 was found in this patient. Heterologous mutation was found in his mother who showed mild diabetes but did not show hirsutism or acanthosis nigricans. These findings suggested that the patient's father had this mutation in his insulin receptor gene and that the homologous mutation gene provoked more severe diabetes mellitus than heterologous mutation in this case. The efficacy of sulfonylurea agents was seen in this patient. Furthermore, sulfonyl urea agents may be indicated for treating these patients, probably by increasing insulin sensitivity. PMID- 8449245 TI - [Analysis of corticoids in adrenal glands by high performance liquid chromatography (HPLC)]. AB - The HPLC system was used to separate and measure 10 kinds of corticoids in adrenal tissues. Calibration curves were drawn as straight lines that ranged from 1.25 to 20ng, or 1.25 to 200ng by peak area calculated with the chromatointegrator. The samples for the assay were extracted from homogenized tissues and treated with methanol to remove non-steroidal contaminants which may interfere with the ultraviolet absorption monitor. The recovery rate during the assay procedure was calculated using testosterone as the internal standard, because testosterone was not detected in any adrenal tissue examined in the present study. Contents of corticoids were measured in normal adrenal glands obtained during radical nephrectomy for renal cancer and in functioning adrenal adenomas. Steroid levels in the adrenal glands and tumors have been measured by radioimmunoassay until now, and the data obtained in the present study were compared with those in previous reports. Main steroids in normal adrenals were cortisol (F) and corticosterone (B), and there were certain amounts of 11 deoxycortisol (S), 11-deoxycorticosterone (DOC) and precursor steroids. 11 beta hydroxy-androstenedione was the main androgen in the adrenal gland. Mineralocorticoids other than B and DOC were very low in the normal adrenals. There was a certain balance between the production of cortisol and corticosterone in normal adrenals. In functioning adenomas, the levels of F, B and aldosterone, and F to B ratios (F/B) varied according to their biological features. Although with the HPLC system it was possible to obtain the production balance of each steroid clearly in the chromatogram, we could not detect the delta 5-3 hydroxysteroids such as pregnenolone and dehydroepiandrosterone using the ultraviolet absorption monitor. PMID- 8449246 TI - [Thyroid hormone metabolism]. AB - Most thyroxine (T4) secreted from the thyroid is deiodinated in peripheral tissues. At least three isozymes are known in iodothyronine deiodinase which catalyzes the conversion of T4 to triiodothyronine (T3) or reverse T3. Type I 5' deiodinase (5'D-I) exists in most tissues including the liver, kidney and thyroid. Type II 5'-deiodinase (5'D-II) which exists mainly in the brain, pituitary, brown fat and placenta plays an important role in the saturation of intracellular T3 receptor. Type III enzyme (D-III) which deiodinases the five positions of T3 is considered to modulate the T3 content by regulating its degradation. The complementary DNA (cDNA) for the rat and human 5'D-I has recently been cloned. 5'D-I contains a rare amino acid selenocysteine, which is essential for normal deiodinative function in humans as well as rats. On the other hand, 5'D-II, whose molecular weight is much heavier than that of 5'D-I, does not contain selenocysteine and its cDNA has not been sequenced. Little is known about the molecular characteristics of D-III. Further studies are needed to clarify the molecular mechanism by which deiodinase proteins are produced in various circumstances and to investigate the meticulous aspects of metabolic pathways other than deiodination. PMID- 8449247 TI - Fetal-maternal immune interaction: blocking antibody and survival of the fetus. AB - In the late 1940s it became clear that the homograft reaction was essentially the result of an immune response. Subsequently, Medawar commented on the apparent paradox of the survival of the mammalian fetus in the face of such a potential (cell-mediated) immune response. In an outbred population the fetal-placental unit will be antigenically different to the mother by virtue of its complement of paternal genes and additionally there may be developmental or stage-specific gene products that are immunogenic. Many mechanisms have been proposed to account for the survival of the fetus in the face of a potential immune attack and, while many of these have been investigated in considerable detail, there has been no clear-cut indication that any one plays a predominant role. Either control of immune rejection of the fetus is exercised by an as yet undiscovered mechanism or, more probably, by a combination of some or all of the mechanisms that have been proposed by many workers over the last three decades. Potential controlling processes, which will be reviewed briefly, include: systemic and local modification of maternal responsiveness; altered expression of MHC antigens on extra-embryonic tissues; the placenta as a barrier; and blocking antibody responses. We discuss some of our recent studies in which we have started to look for potential blocking antibodies in a mouse model system. Cells secreting immunoglobulins M and G, characterized in hemolytic plaque assays, have been mapped to areas close to the midgestation mouse embryo, using an immunocryohistological technique. A scaled-down version of hybridoma technology has been used as an analytical probe of the specificity and isotype of immunoglobulin secreted by cells originating either from close to the embryo/fetus or from the para-aortic lymph nodes (PALN). So far monoclonal (IgG1) antibodies with specificity for embryonic cells have been derived together with some monoclonal immunoglobulins with as yet uncharacterized antibody specificity. PMID- 8449248 TI - Cytotoxic activity of Ciona intestinalis (Tunicata) hemocytes: properties of the in vitro reaction against erythrocyte targets. AB - Hemocytes (effectors) of Ciona intestinalis showed a natural cytotoxic capacity (HCA) when assayed in vitro against erythrocytes (targets). Cytotoxic cells lysed, to a variable extent, rabbit (RE), human (A, B, O), guinea pig, and sheep (SE) erythrocytes. Hemocyte cytotoxic activity (HCA) assayed against SE is a calcium-dependent reaction, occurs rapidly (15-30 min), at 25-37 degrees C over a wide range of pH (5.4-8.0). Assays were carried out using: 1) the medium in which hemocytes were maintained, 2) the soluble portion of hemocyte lysates, and 3) debris prepared from hemocyte lysates. Results suggest that HCA is a cell mediated process that requires effector-target cell contacts. Anti-SE (calcium dependent) and anti-RE (calcium-independent) agglutinins were also found in the reaction medium, probably released by hemocytes as a consequence of the in vitro experiments. The occurrence of HCA was independent of any allogeneic reaction between mixed hemocytes. Various levels of cytotoxic activity reveal hemocyte specificity. PMID- 8449249 TI - A humoral opsonin from the solitary urochordate Styela clava. AB - Opsonins play a key role in invertebrate humoral immune systems. An opsonin for yeast was identified in the plasma of the tunicate, Styela clava. In vitro cultures of hemocytes with homologous plasma-incubated yeast exhibited significantly higher levels of phagocytosis than controls. Studies indicated that the opsonic activity of Styela clava plasma increased the overall capacity for phagocytosis. Opsonization was inhibited by the carbohydrates mannan, N-acetyl-D galactosamine, and galactose, and by the divalent cation chelator, EDTA. These data suggest that the Styela clava opsonin may share some functional similarities with a C-type lectin. Incubation of yeast with Styela clava and Styela plicata plasma prior to phagocytosis by hemocytes from both species indicated the Styela clava opsonin is species specific. PMID- 8449250 TI - Antibody production in sharks and humans: a role for natural antibodies. AB - Although gene segments specifying Igs of all vertebrates show clear homology, their arrangements differ markedly, thereby suggesting that the mechanisms for the generation of diversity and for the regulation of gene expression may be quite distinct. In the sandbar shark, light chain gene segments are distributed as apparently independent clusters consisting of V, J, and C elements that require rearrangement for expression. The usual distance between V and C in the clusters is 3 kb but larger clusters occur. The V, J, and C elements are clearly homologous to those of human lambda chains. Shark Igs resemble mammalian IgM in structure and gene similarity. IgM may comprise as much as 50% of serum proteins in the shark. By contrast, IgM in humans comprises less than 5%. Human autoantibodies usually are IgM. These show little dependence on thymic function for expression and tend to increase with age. We have carried out a study of the capacity of Igs of unimmunized sharks and people (normals and patients suffering from autoimmune diseases) to react against a panel of antigens, including those usually considered autoantibodies, such as thyroglobulin and single-stranded DNA. Sharks and humans possess IgM antibodies that react with thyroglobulin and ssDNA. Affinity-purified natural shark antibodies to thyroglobulin or ssDNA constitute small fractions of total IgM. They illustrate extensive cross-reactivity comparable to that shown by polyspecific IgM autoantibodies produced by human B cells (CD5+) that appear early in ontogeny. PMID- 8449251 TI - The gut-associated lymphoid tissue (GALT) of carp (Cyprinus carpio L.): an immunocytochemical analysis. AB - The GALT of carp was studied with monoclonal antibodies reacting with carp Ig or carp leukocytes, using (dual) immunofluorescence or immunogold staining on cryosections, cytocentrifuge slides, and cell suspensions of the intestine. The intestinal epithelium contained many Ig-negative lymphoid cells and, in the hindgut, also many large Ig-positive macrophages, which appeared to bind Ig. The lamina propria contained numerous Ig-positive lymphoid cells next to Ig-negative lymphoid cells and granulocytes. Leukocytes isolated from the intestine mainly consisted of Ig-negative lymphoid cells (> 90%). With the methods used, leukocytes were poorly released from the connective tissue. Nevertheless, two types of Ig-containing cells were found: a conventional plasma cell, frequently showing Ig at its surface, and a more common smaller lymphoid cell having a narrow rim of Ig-positive cytoplasm but hardly any Ig on its surface. Many of the Ig-positive lymphoid cells observed in the lamina propria may represent these small Ig-containing cells. Isolated Ig-positive macrophages were frequently associated with B- and T-like cells. Our data strongly suggests an immunological function for the gut of carp, especially for the antigen-transporting hindgut. PMID- 8449252 TI - Domain structure, functional activity, and polymerization of trout complement protein C9. AB - The 3' region of trout C9 has been resequenced and found to differ from the previously published sequence (Stanley and Herz, EMBO J. 6:1951; 1987). In contrast to other sequenced C9 molecules, but in common with the other terminal complement components, trout C9 was found to contain an additional carboxy terminal thrombospondin domain. This domain does not restrict polymerization, as has been previously suggested (Stanley and Luzio, Nature 334:475; 1988), since alternative pathway activation of trout complement by rabbit erythrocytes lead to the formation of circular membrane attack complement lesions on the erythrocyte membrane. Although the trout C9 molecule is larger than human C9, the diameters of circular trout membrane attack complexes were approximately 30% smaller than their human counterparts. No lysis of erythrocytes bearing human C5b-7 or C5b-8 complexes was detected following incubation with trout serum containing EDTA, which suggests that trout C8 and C9 are unable to bind to human C7 and C8, respectively. Finally, trout and human serum were equally effective at killing the human serum-sensitive strain Salmonella minnesota Re595. PMID- 8449253 TI - Anti-S-100 antibody recognizes ellipsoid-associated cells and other dendritic cells in the chicken spleen. AB - The chicken spleen was studied immunohistochemically with anti-S-100 protein polyclonal antibody. S-100-positive cells accumulated around the penicilliform capillaries during the first 3 weeks of life. After 2 weeks posthatch the S-100 positive cells appeared in the red pulp, periarterial lymphatic sheath, and subsequently in the germinal center. Their ontogenetic development and intrasplenic distribution strongly suggested that the S-100-positive cells were identical with ellipsoid-associated cells. The S-100-negative cells of the periellipsoidal white pulp gradually transformed to S-100-positive, functionally active cells on the surface of the ellipsoid. The immunohistological findings support the hypothesis that the interdigitating dendritic cells and follicular dendritic cells were not of monocytic origin but belong to a splenic resident, endocytic cell line located on the surface of the ellipsoid. PMID- 8449254 TI - The effect of synthetic thymulin on cell surface marker expression by avian T cell precursors. AB - The effects of the in vitro exposure of avian bone marrow (BM) cells and thymocytes to synthetic thymulin were studied. Two T-cell differentiation markers, PNA binding site and CT-1a expression, were used to examine cell maturation. Enhanced PNA binding to both BM cells and thymocytes resulted following an in vitro thymulin exposure but cell proliferation was not affected. Scatchard analysis supported the conclusion that PNA binding affinity was significantly increased and thus responsible for the observed increase in PNA binding. Flow cytometric analysis suggested that the induced PNA+ thymocyte population may be a different population from the one exhibiting enhanced CT-1a expression following thymulin exposure. Taken together, the observations suggest that cells can express their further differentiation states without undergoing proliferation following in vitro thymulin stimulation. PMID- 8449255 TI - Caesarean section survey in Galway--1973 through 1987. AB - We review the trend, indications and maternal mortality with caesarean section at University College Hospital Galway from 1973 to 1987. The caesarean section rate (CSR) rose from 6.06% in 1973 to 10.18% in 1987, primary sections from 3.58% to 6.51% and repeat sections from 2.49% to 3.67% during the same interval. The four major indications for section were cephalopelvic disproportion, foetal distress, previous section and malpresentations. Lower segment caesarean section was the commonest operation and a slight increase in the classical operation was noted due to an increased intervention in prematurity. The maternal mortality rate was 11.2/10,000 in the 15-year period and the complications leading to death were ultimately ascribable to primary postpartum haemorrhage. Strategies for reduction in the CSR are discussed. PMID- 8449256 TI - Risk factors for major obstetric haemorrhage. AB - The factors associated with major obstetric haemorrhage were analyzed using data relating to 37,497 women delivered in 1988 in National Health Service maternity units in the North West Thames Region, UK. Four hundred ninety-eight cases (1.33%) were complicated by haemorrhage of 1000 ml or more. Intrinsic factors associated with significant risk ratios (99% confidence intervals) included placental abruption 12.6 (7.61-20.9), placenta praevia 13.1 (7.47-23.0), multiple pregnancy 4.46 (3.01-6.61) and obesity 1.64 (1.24-2.17), but not high parity. Significant risk factors related to obstetric management and delivery included retained placenta 5.15 (3.36-7.87), induced labour 2.22 (1.67-2.96), episiotomy 2.06 (1.36-3.11) and birthweight 4 kg or more 1.90 (1.38 to 2.60). Among the 59 women who lost 1000 ml or more in association with a spontaneous vaginal delivery with an intact perineum, significant risk ratios (99% confidence intervals) were retained placenta 13.7 (5.92-31.8) and induced labour 2.35 (1.11-4.98). These data provide a more comprehensive assessment of risk factors for potentially life threatening haemorrhage in British obstetric practice than is possible using maternal mortality statistics. The hazards of well known factors such as multiple pregnancy, abruption, placenta praevia and caesarean delivery were confirmed but attention is drawn to the potential risk of haemorrhage associated with obesity or a large baby and to that associated with retained placenta in women classified as 'low risk'. PMID- 8449257 TI - Management of the third stage of labour in women at low risk of postpartum haemorrhage. AB - OBJECTIVE: To compare active management with physiological management of the third stage of labour in women at low risk of postpartum haemorrhage. DESIGN: Randomised allocation of women in labour at low risk of postpartum haemorrhage to either physiological or active management of the third stage. SETTING: Labour ward in a district general hospital. PATIENTS: 193 Women with spontaneous vaginal delivery at term completed the study. Exclusion criteria were induction or augmentation of labour, antepartum or previous postpartum haemorrhage, premature rupture of membranes, previous caesarean section, raised blood pressure, cervical lacerations and third degree tears. INTERVENTIONS: Active management with syntometrine and controlled cord traction; or physiological management, where the cord was not clamped and the placenta was delivered by maternal effort. MEASUREMENTS: Blood loss was measured subjectively at delivery and estimated objectively by comparing the haemoglobin in labour with that on the third postpartum day. The duration of the third stage was also measured as was the incidence of retained placenta and blood transfusion. RESULTS: There was no significant difference in the estimated blood loss or haemoglobin drop between the two groups (P > 0.5). In addition the duration of the third stage was significantly longer in the physiological group (P < 0.001). Out of 90 women having physiological management, 7 received oxytocics for presumed postpartum haemorrhage. Only one case in the active group required further oxytocics and one other case in this group required a manual removal of placenta. CONCLUSIONS: This preliminary study confirms that active management results in a reduction in the length of the third stage of labour. However, it suggests that active management does not reduce blood loss when compared to physiological management in the woman at low risk of postpartum haemorrhage. PMID- 8449258 TI - The relationship between urinary Tamm-Horsfall glycoprotein excretion and urinary activity of glycosidases in normal pregnancy and pre-eclampsia. AB - Electrophoretic analyses of the urinary proteins of pre-eclamptic patients revealed a decrease in the staining intensity of the protein band representing the Tamm-Horsfall glycoprotein (THP). In the present study the quantitative analysis of the THP excretion rate and the urinary activity of THP oligosaccharide metabolizing glycosidases were investigated. The median THP excretion rate of non-pregnant women (n = 24) was 20 mg/g creatinine (crea.). An increase in the THP excretion rate was seen in pregnancy to a level between 43 mg/g crea. (II. trimester) and 32 mg/g crea. (III. trimester) (n = 29). Hypertension in pregnancy was associated with a decrease in the THP excretion rate to 9 mg/g crea. (n = 85). Post partum, a transient elevated THP excretion rate up to 109 mg/g crea was recorded in the group of hypertensive patients. The urinary activities of the lysosomal beta-mannosidase, alpha-fucosidase, alpha mannosidase (pH 4.5) and beta-galactosidase increased in normal pregnancy. This effect was most pronounced in the beta-galactosidase activity which increased from 50 U/mg crea. before pregnancy to 280 U/mg crea. at term. Hypertension in pregnancy was associated with a further increase in the activities of the lysosomal glycosidases. In the case of the beta-galactosidase a significant rise from 68 to 310 U/mg crea. was found. The urinary activity of the alpha mannosidase (pH 5.5) originating from the Golgi apparatus was only elevated in patients with severe pre-eclampsia. Casuistic post partum recordings demonstrated that an elevation of the lysosomal glycosidases activities was followed by a transient increase in the THP excretion rate. PMID- 8449259 TI - Risk factors for groin node metastasis in squamous carcinoma of the vulva: a multivariate analysis of 39 cases. AB - This study includes 39 patients with squamous carcinoma of the vulva subjected to radical surgery. Stage, tumor description, cell type, lesion localization, lesion size, depth of invasion, grade, lymphovascular space invasion, number of mitoses, degree of stromal inflammatory reaction, and tumors in surgical margins were analyzed for groin metastasis. Of the factors analyzed, stage (P = 0.018), grade (P = 0.007) and depth of invasion (P = 0.001) were found to be the most important predictors of node metastasis. While a combination of factors permitted to define a low-risk group with 0% node metastasis, it seems hard to identify preoperatively those patients with no risk of nodal metastasis. PMID- 8449260 TI - How well do perimenopausal patients accept outpatient hysteroscopy? Visual analogue scoring of acceptability and pain in 100 women. AB - There is growing interest in performing hysteroscopic examination of the uterine cavity as an outpatient procedure. Its sensitivity and specificity in detecting uterine abnormalities are well recognised. This study assessed how outpatient hysteroscopy was tolerated and accepted by 100 women attending a hospital-based menopause clinic. Patients were asked to complete a questionnaire following an outpatient hysteroscopy. Using visual analogue scoring (0 = no pain/completely acceptable, 10 = worst pain imaginable/completely unacceptable), the mean maximum pain experienced during the procedure was 3.25 (S.D. 2.08) and the degree of acceptability was 3.02 (S.D. 1.96). Three percent (N = 3) of patients stated they would prefer a repeat hysteroscopy to be performed under general anaesthetic and 3% (N = 3) of patients stated they would prefer an inpatient stay following a repeat hysteroscopy. These findings demonstrate that outpatient hysteroscopy is well tolerated by perimenopause patients. The advantages of outpatient hysteroscopy to the perimenopausal woman are discussed. PMID- 8449261 TI - Inflammatory reaction in endometriotic tissue: an immunohistochemical study. AB - A panel of monoclonal antibodies specific for macrophage subtypes appearing in early (27E10), down-regulatory (RM3/1) and late (25F9) stages of inflammation had been applied to 20 endometriotic implants of 14 women. Of those patients 9 were in the follicular phase of the cycle, two on danazol, one on LHRH-analogue (buserelin) and another two on oral contraceptives. Beside the macrophage subsets, antibodies against T4, T8 lymphocytes as well as proliferating cells (EN7/44 and Ki67) were examined. In all specimens immunologically competent cells could be detected to a varying degree and within the same implant different stages of inflammation were discernible. Endometriosis presented with signs of early inflammation indicated by 27E10+ macrophages and CD4+ lymphocytes (15 specimens) and with down-regulatory, late inflammatory reactions as shown by RM3/1+, 25F9+ macrophages and CD8+ lymphocytes (19 biopsies). Additionally, in 14 specimens cells of the EN7/44+ and Ki67+ type was detected. These preliminary results showed no significant correlation to either extension of endometriotic implants or adhesions or concomitant therapy and clearly indicate, that there is an immunological dynamic process within the lesion itself in addition to that one of the peritoneal fluid. PMID- 8449262 TI - Postoperative adhesion after uterine horn surgery in the rat, with the use of TC7. AB - The influence of TC7 in adhesion prevention was tested on 24, 2.5-month-old Wistar rats. Their right and left uterine horns were homogeneously allotted into four experimental groups, each of 12 horns. The groups were as follows: Group C (n = 12), that underwent cuts along 1 cm in the serosal layer; Group TC (n = 12), where the uterine horn was only surrounded with 3 layers of TC7, 1 x 1 cm in size; Group C+TC (n = 12) in which the serosal cuts were covered with TC7, as in group TC and an untouched control group (n = 12). All uterine horns were kept in uniform contact with the intestinal serosa layer by means of two 8/0 nylon stitches spaced 2 cm apart, so that the adhesion surfaces were the same in all groups. Lengths in mm and severity adhesions (0 = no adhesion to 3 = severe adhesion) were recorded. The injury in group C caused extensive (8.83 +/- 4.77 mm) and dense adhesions (score 2.42 +/- 1.11) in 83.33% of the cases. No significant differences were observed compared with the C+TC group (8.08 +/- 5.45 mm, score 2.25 +/- 1.30; P > 0.05, ANOVA). Significantly, more adhesions were observed on the C and C+TC Groups than in the control (1.00 +/- 2.27 mm, score 0.16 +/- 0.37) and TC (3.08 +/- 3.38 mm, score 1.00 +/- 1.15) groups (P < 0.05, ANOVA). TC7 does not appear to be an effective agent for preventing postoperative adhesions in this animal model. PMID- 8449263 TI - Low-dose progesterone therapy in oestrogenised postmenopausal women: effects on plasma lipids, lipoproteins and liver function parameters. AB - BACKGROUND: Cardiovascular disease among older women is a major health problem and is the leading cause of death in this group in developed countries. The risk is reduced in oestrogen users secondary to favourable lipid changes, but the beneficial effect of oestrogen may be counteracted when concomitant progestogens are administered. OBJECTIVE: To study the effects of a novel hormone replacement therapy regimen on liver enzymes, lipids and lipoproteins in postmenopausal women. DESIGN: Prospective open, non-comparative trial for 12 months. METHODS: 40 healthy postmenopausal women, (mean age +/- S.D.), 53.5 +/- 3 years received 0.625 mg of conjugated equine oestrogen daily and 100 mg of micronised oral progesterone (P) for the first 23 days every calendar month for 12 months without interruption. MAIN OUTCOME MEASURE: Gonadotrophins, liver function parameters and lipoproteins were measured before treatment and at the 6th, 9th and 12th months of treatment. RESULTS: Compliance with treatment was confirmed by a 33% decrease in mean serum level of follicle stimulating hormone at the end of 1 year of treatment. In the same period, the mean serum cholesterol, LDL and LDL/HDL ratio decreased by 6%, 16% and 23% of the base line levels, respectively. The percentage changes in triglycerides and HDL from the basal levels were +32% (P < 0.001) and +15% (P < 0.05), respectively. CONCLUSION: These results indicate that near continuous administration of fixed low-dose of P has no adverse effects on the lipid milieu of postmenopausal women when combined with long-term continuous oestrogen replacement therapy provided women with borderline triglyceridaemia are excluded. PMID- 8449264 TI - Combined bilateral tubal and multiple intrauterine pregnancy after ovulation induction. AB - Over the last 20 years, the frequency of multiple pregnancy has increased mainly because of the introduction of exogenous pituitary gonadotropins in the treatment of sterility. The incidence of ectopic pregnancies also increased during the same period of time. This paper describes the first reported case of a simultaneous bilateral tubal and multiple intra-uterine pregnancy after ovulation induction with human gonadotropins. PMID- 8449265 TI - Highly elevated serum CA 125 levels in a patient with cardiac failure. AB - Presented is a case story of a patient with highly elevated serum levels of the tumour marker CA 125 (Cancer Antigen 125). The patient was thought to have ovarian cancer, but eventually the source of the elevated serum CA 125 levels became clear: cardiac failure caused by thyrotoxicosis. Benign and malignant causes of elevated serum levels of CA 125 are described briefly. PMID- 8449266 TI - Prenatal sonographic diagnosis of fetal hepatic hemangioma. AB - Although hepatic hemangioma represents the most common tumor of the liver during childhood, the prenatal diagnosis of this condition has been rarely reported in the literature. In this report, we describe a case of hepatic hemangioma presenting as a small hyperechogenic mass (1.1 x 0.9 cm) in the fetal liver in which the diagnosis was made at 33 weeks' gestation by ultrasound. Subsequent postnatal evaluation by Doppler ultrasound confirmed the diagnosis and follow-up examinations have documented its spontaneous regression. The prenatal diagnosis of a liver mass allows not only the evaluation of changes in size or pattern of the mass itself during pregnancy but also its prompt evaluation after birth. PMID- 8449267 TI - Caesarean section audit by peer review. AB - OBJECTIVE: To provide activity audit data on 50 consecutive caesarean sections and assess the justification for the decision to perform each caesarean section. DESIGN: A retrospective audit with peer review. SETTING: Aberdeen Maternity Hospital. SUBJECTS: Fifty consecutive women undergoing caesarean section. The peer review was undertaken by four consultants and four registrars. MAIN OUTCOME MEASURES: The proportions of caesarean sections by indication stratified according to primiparae or multiparae and emergency or elective procedures. The auditors were asked 'do you think caesarean section was reasonable?' RESULTS: There were 18 (36%) elective caesarean sections and 32 (64%) emergency procedures. Of the 25 (50%) parous women, 14 (56%) had a previous caesarean section and of these 12 (86%) had an elective repeat caesarean section. Foetal distress was the principal indication for emergency caesarean section in 20 (63%) women, with foetal blood sampling performed in only four cases. For emergency caesarean sections the decision to delivery interval ranged from 13 to 160 min (mean 50 min). At least one auditor disagreed with the decision to perform caesarean section in 24 (48%) cases. Between observers the range of disagreement was from 2 to 18 of the decisions. In only 6 (33%) of the 18 elective procedures was there complete agreement. Four (67%) of these women had two previous caesarean sections. There was complete agreement with 20 (63%) of the 32 emergency caesarean sections. Conclusions--Interventions considered as a result of this audit include the introduction of structured diagnostic criteria for caesarean section indications and peer review by the on-call team of the caesarean sections performed in the preceding 24 h. PMID- 8449268 TI - 2'-O-alkyloligoribonucleotides: probes for studying the biochemistry and cell biology of RNA processing. AB - Chemical synthesis of 2'-O-alkyloligoribonucleotides has been developed and shown to have important applications in the study of RNA processing and the analysis of structure-function relationships in RNA molecules. Antisense oligonucleotides made of 2'-O-alkyl RNA are nuclease-resistant and form extremely stable and specific hybrids with complementary RNA target sequences. This makes them very useful probes for labelling RNAs, for functional studies on the mechanism of RNA processing reactions and for affinity chromatography of RNA-protein complexes. The use of 2'-O-alkyloligoribonucleotides thus provides an important alternative strategy to immunological methods for biochemists wishing to modify, purify, deplete, inactivate or in situ-label RNAs or RNPs. I very much hope that the work I have described here may have helped to stimulate other workers in the RNA field to consider applying these techniques to further their own research interests. PMID- 8449269 TI - The relationship between structure and activity of the methoxyacrylate toxophore. PMID- 8449270 TI - Characterisation of DNA methylase from pea (Pisum sativum). PMID- 8449271 TI - Excitatory amino acid antagonists and epilepsy. PMID- 8449272 TI - The role of DNA methylation in the expression of parathyroid hormone-related protein in humoral hypercalcaemia of malignancy. PMID- 8449273 TI - Fluorescence-based DNA segment analysis in forensic science. PMID- 8449274 TI - Fluorophore-assisted carbohydrate electrophoresis: a new technology for the analysis of glycans. PMID- 8449275 TI - Studies of binding equilibria for peptides and pharmaceuticals using capillary electrophoresis. PMID- 8449276 TI - The role of intracellular free calcium and phosphorylation in survival and differentiation of cultured cerebellar granule cells. PMID- 8449277 TI - Two-dimensional electrophoresis with immobilized pH gradients: current state. PMID- 8449278 TI - Fascinating families of proteins: electrophoresis of human saliva. PMID- 8449279 TI - New molecular perspectives in islet hormone biosynthesis. PMID- 8449281 TI - Light harvesting in photosystems I and II. PMID- 8449280 TI - Growth of the endocrine pancreas: the role of somatolactogenic hormones and receptors. PMID- 8449282 TI - Positive and negative regulation of insulin gene transcription. PMID- 8449283 TI - Cell-specific gene expression in the islets of Langerhans: E boxes and TAAT boxes. PMID- 8449284 TI - Evolutionary conservation of elements in the upstream glucokinase promoter. PMID- 8449286 TI - Formation of islet amyloid from islet amyloid polypeptide. PMID- 8449285 TI - Pancreatic beta-cells express a low affinity glucose transporter: functional consequences in normal and diabetic states. AB - The application of molecular biology to the study of membrane transport proteins has led to a rapid advance in our understanding of the mechanisms behind the regulation of blood glucose levels. Moreover the demonstration of lesions in the expression of GLUT2 in the islets from diabetic models has provided a focus for research efforts aimed at addressing the defects responsible for the development and onset of both type I and perhaps type II diabetes. The recent demonstration that an 'artificial beta-cell' can be engineered from anterior pituitary-derived cell lines by transfection with both the insulin cDNA and the cDNA encoding GLUT2 represents a significant advance in the development of potential therapies for type I diabetes [24]. PMID- 8449287 TI - Interaction of guanyl nucleotides with [3H]kainate binding in goldfish brain. PMID- 8449288 TI - Differential islet cell expression of two glutamate decarboxylases, both autoantigens in diabetes. PMID- 8449289 TI - Characterization of a cDNA encoding the insulin gene GAGA-binding factor, Pur-I. PMID- 8449290 TI - Cyanobacterial photosystem I structure. PMID- 8449291 TI - Capillary electrophoresis (CE) of proteins with scanning detection. PMID- 8449292 TI - The carbamoyl phosphate synthetase-aspartate transcarbamoylase complex of Saccharomyces cerevisiae: molecular and cellular aspects. PMID- 8449293 TI - Interactions of the myxothiazol and mucidin toxophores with cytochrome b. PMID- 8449294 TI - Overview of multienzyme systems in biosynthetic pathways. PMID- 8449295 TI - Oxidative amino aid processing in beta-lactam antibiotic biosynthesis. PMID- 8449296 TI - Role of protein kinase C in the chronic insulin-antagonistic effects of growth hormone in sheep adipose tissue. PMID- 8449297 TI - The organization of multifunctional peptide and depsipeptide synthetases. PMID- 8449298 TI - The erythromycin-producing polyketide synthase. PMID- 8449299 TI - Prediction of key structural features in the polypeptides of photosystems I and II. PMID- 8449300 TI - Human insulin promoter driven reporter gene expression. PMID- 8449301 TI - The biosynthesis of tetraketides: enzymology, mechanism and molecular programming. PMID- 8449302 TI - Investigation of a novel GABAergic cell-surface marker which may link Stiff Man's syndrome and insulin-dependent diabetes mellitus. PMID- 8449303 TI - Linkage of maturity-onset diabetes of the young to the glucokinase gene--evidence of genetic heterogeneity. PMID- 8449304 TI - A new ELISA for specific insulin measurements in type II diabetic patients. PMID- 8449305 TI - Structural organization of complex I from bovine mitochondria. PMID- 8449306 TI - Localisation of islet amyloid polypeptide (IAPP) in pancreatic islets of transgenic mice expressing the human or rat IAPP gene. PMID- 8449307 TI - Endothelin converting enzyme of porcine lung. PMID- 8449308 TI - IAPP/amylin transgenic mice as an in vivo model system for type-2 diabetes mellitus? PMID- 8449309 TI - Phosphorylation patterns from thylakoid peptides from Synechococcus 7942 under nitrogen repleted and depleted conditions. PMID- 8449310 TI - Mutagenesis of the dehydratase active site in the erythromycin-producing polyketide synthase. PMID- 8449311 TI - Import and sorting of proteins by chloroplasts. PMID- 8449312 TI - Analysis of a gene cluster from S. longisporoflavus potentially involved in tetronasin biosynthesis. PMID- 8449313 TI - 6-Deoxyerythronolide B synthase 3 from Saccharopolyspora erythraea: over expression in Escherichia coli, purification and characterisation. PMID- 8449314 TI - Construction of an artificial 'multicatalytic protease'. PMID- 8449315 TI - A unique, membrane-bound, multifunctional enzyme from human liver mitochondria catalysing three steps of fatty acid beta-oxidation. PMID- 8449316 TI - Modelling alpha-helical transmembrane domains. PMID- 8449317 TI - Comparisons of nucleotide and protein sequences for mammalian serine hydroxymethyltransferase. PMID- 8449318 TI - The viscoelastic moduli of actin/filamin solutions: a micro-rheologic study. PMID- 8449319 TI - Dihydrolipoamide dehydrogenase in plants: differences in the mitochondrial and chloroplastic forms. PMID- 8449320 TI - A progress report on the crystallographic studies on the B800-850 antenna complex from Rhodopseudomonas acidophila strain 10050. AB - Large single crystals (up to 1 mm in each dimension) of the B800-850 antenna complex from Rhodopseudomonas acidophila strain 10050 have been grown in the presence of beta-octyl-glucoside. These crystals have the space group R32 and unit cell dimensions of a = b = 119.9 A and c = 297.0 A. Recently we have improved our crystallization procedures so that all crystals now diffract reliably to beyond 3.5 A, with some diffracting to below 3 A. A range of isomorphous heavy atom derivatives have been prepared and we are now engaged in locating the heavy atom sites within the unit cell. PMID- 8449321 TI - Crystallisation of the B800-820 light-harvesting complex from Rhodopseudomonas acidophila strain 7750. PMID- 8449322 TI - Comparative sequence analysis and predicted phylogeny of the DNA-dependent RNA polymerase beta subunits of Staphylococcus aureus and other eubacteria. PMID- 8449323 TI - Protein engineering of bacterial light-harvesting complexes. PMID- 8449324 TI - Inositol-containing lipoglycans in prokaryotes. PMID- 8449325 TI - A glycosyl-phosphatidylinositol anchor can target a bacterial enzyme to the apical surface of polarized epithelial cells. PMID- 8449326 TI - Probing the donor side of bacterial reaction centres: site-directed mutants of tyrosine L162 of Rhodobacter sphaeroides and Rhodopseudomonas viridis. PMID- 8449327 TI - The structure of the glycosylphosphatidylinositol anchor from Torpedo californica acetylcholinesterase. PMID- 8449328 TI - Identification of the site of attachment of the glycolipid anchor in porcine membrane dipeptidase. PMID- 8449329 TI - Investigation of glycolipid anchor addition using a synthetic peptide as substrate. PMID- 8449330 TI - Structural determination of the glycolipid anchors of human and porcine membrane dipeptidases. PMID- 8449331 TI - Intracellular compartmentalisation of procorticotrophin releasing hormone. PMID- 8449332 TI - A 70 kDa Aeromonas salmonicida serine protease - beta-galactosidase hybrid protein as an antigen and its protective effect on Atlantic salmon (Salmo salar L.) against a virulent A. salmonicida challenge. PMID- 8449333 TI - The lipids of Rhodopseudomonas acidophila strain 10050 as possible influences on the crystallisation of the B800-850 complex from this bacterium. PMID- 8449334 TI - Effect of 5-fluorouracil on polyamine excretion in human colonic cancer cells. PMID- 8449335 TI - In vitro biochemical activities associated with recombinant HIV-1 integrase. PMID- 8449336 TI - Amorphous aluminosilicates promote nucleation of amyloid beta protein and tachykinins. PMID- 8449337 TI - Immunoaffinity purification of synaptosomes and PC12 cells expressing cell surface APP. PMID- 8449338 TI - Models of APP dysfunction in Alzheimer's disease. PMID- 8449339 TI - Evidence for more than one binding site in cloned D2 and D3 dopamine receptors. PMID- 8449340 TI - Studies on cervical glycoproteins: isolation and characterisation of oligosaccharides from luteal phase cervical glycoproteins of bonnet monkey. PMID- 8449341 TI - Quantifying the value of biological information: II. PMID- 8449342 TI - The effect of changes in light intensity and temperature on the peripheral antenna of Rhodopseudomonas acidophila. PMID- 8449343 TI - Artificial generation of oxygen radicals and cell damage in the heart. PMID- 8449344 TI - Nuclear signal transduction via immediate early genes in neurons and glia. PMID- 8449345 TI - Alterations of rat kidney, liver and erythrocytes glucose 6-phosphate dehydrogenase activity by chronic acidosis. PMID- 8449346 TI - Allosteric properties of yeast pyruvate kinase studied by site-directed mutagenesis. PMID- 8449347 TI - Purification and partial characterisation of a protein of unknown function from Thermoplasma acidophilum. PMID- 8449348 TI - The effects of pH on the binding of ATP and phosphate in the biotin carboxylation reaction of pyruvate carboxylase. PMID- 8449349 TI - Investigating the function of cytochrome P450 BM-3: a role for the phylogenetically conserved tryptophan residue? PMID- 8449350 TI - Scheme of RNA transcription in calicivirus-infected cells. PMID- 8449351 TI - Antioxidants prevent nickel chloride inhibition of cytochrome P450 dependent mixed function oxidation in guinea pig lung microsomes. PMID- 8449352 TI - Cloning the pea DNA methylase cDNA. PMID- 8449353 TI - Maintenance of liver-specific function in cultured hepatocytes in different media. PMID- 8449354 TI - Identification of transferrin in cytosol isolated from intestinal mucosal cells. PMID- 8449355 TI - Comparison of substrata for culture of mouse mammary cells. PMID- 8449356 TI - Dendroaspin: a potent integrin receptor inhibitor from the venoms of Dendroaspis viridis and D. jamesonii. PMID- 8449357 TI - Maintenance of GSH content in primary astrocyte cultures under oxidative stress conditions. PMID- 8449358 TI - Metabolism and function of brain kynurenines. PMID- 8449359 TI - Studies on CpG methylation within human tRNA(Gly) genes. PMID- 8449360 TI - Metabolism and neuropathologic significance of quinolinic acid and kynurenic acid. PMID- 8449361 TI - Fourier transform infrared spectroscopy as a probe for the study of the structure of membrane proteins. PMID- 8449362 TI - Interactions between nerve and muscle: synapse elimination at the developing neuromuscular junction. AB - Studies of synaptogenesis at the developing neuromuscular junction have provided a wealth of information regarding the various mechanisms that are involved in the formation of synaptic connections. In addition to synapse formation, however, the mature pattern of innervation at the neuromuscular junction (and elsewhere in the nervous system) depends on a significant loss of synaptic connections during development. The molecular mechanisms involved in the process of synapse elimination are not understood. Recent work at the neuromuscular junction suggests that changes in the postsynaptic cell may be necessary in order for nerve terminals to be eliminated. Thus, in contrast to synapse formation in which an axon terminal initiates a cascade of changes leading to the formation of pre- and postsynaptic specializations, synapse elimination may be initiated by local changes in the postsynaptic cell that disassemble the postsynaptic apparatus and ultimately remove the overlying terminal. In this review, we wish to examine the potential role that some of the factors involved in synapse formation might play in the less-well-understood phenomenon of synapse elimination. PMID- 8449363 TI - Myogenic regulatory factors: dissecting their role and regulation during vertebrate embryogenesis. AB - The elucidation of the myogenic regulatory factors (MRFs) has resulted in a surge of research activity that promises to bridge molecular and embryological approaches to muscle research. In this review, we consider the arguments that would place MRFs in a key determination role for the skeletal muscle lineage in the vertebrate embryo. Amphibian, avian, and murine systems are compared and recent developments in the molecular embryology of myogenesis are reviewed. A model is proposed to account for the apparent discrepancies in conclusions drawn from studies using cultured cells that indicate a role for the MRFs in determination, and studies of MRF and muscle gene expression in vivo that indicate a role in differentiation but not in lineage determination. PMID- 8449364 TI - Neurons producing specific neuropeptides in the central nervous system of normal and pupariation-delayed Drosophila. AB - Antibodies generated against bombyxin and prothoracicotropic hormone (PTTH) of Bombyx mori and allatotropin, allatostatin, and diuretic hormone (DH) of Manduca sexta react with distinct sets of cells in the central nervous system of Drosophila larvae, pupae, and adults. Brain neurons immunoreactive with antibodies to bombyxin, PTTH, and DH are in strikingly similar positions to their lepidopteran counterparts, indicating that at least some Drosophila neuroendocrine cells are homologous to those of lepidopterans. Allatotropin and allatostatin-immunopositive neurons of Drosophila differ from those of lepidopterans, but many of them are identical with neurons that express the FMRFamide gene. Antibodies to bombyxin, PTTH, allatostatin, and DH also stain axons and axon terminals in the neurohemal part of the ring gland, and all tested antibodies except that against bombyxin show positive reaction in the neurohemal area of the ventral ganglion. Although immunoreactivity with all antibodies is variable during development, the highest levels of staining are found at developmental stages when the neuropeptides would be expected to be functioning. A genetic analysis of neuropeptide expression and function has been initiated by analyzing immunoreactivity in mutants that have prolonged larval life associated with imaginal disc overgrowth. Two of these mutants, dlg and dco, show abnormally strong immunoreactivity for allatotropin during the extended larval period and the former also show increased staining with the PTTH antibody. The reduced ecdysteroid titer and delayed or blocked metamorphosis in the mutants may be a result of altered neuropeptide production, which is probably secondary to the imaginal disc overgrowth. PMID- 8449365 TI - Involvement of protein kinase C in nuclear migration during compaction and the mechanism of the migration: analyses in two-cell mouse embryos. AB - Compaction and nuclear migration occur in mouse embryos at the late eight-cell stage. It has been reported that activators of protein kinase C (PKC) increase adhesion of cells at the two-cell, four-cell, and uncompacted eight-cell stage. We report here that nuclear migration followed the increased adhesion of cells in such embryos when they were treated with PKC activators. These cellular events resembled those in normal embryos at the late eight-cell stage and were blocked by sphingosine, a PKC inhibitor. The responses were proportional to the dose of the PKC activator. Molecular analogues of the PKC activators, which do not affect PKC, did not induce these events. These results suggest an important role for PKC in initiation of nuclear migration as well as in compaction. Experiments were also conducted to identify the source of the mechanical force that moves the nucleus. Nuclear migration was suppressed in embryos pretreated with colchicine. Calmodulin is known to have effects on Ca(2+)-induced assembly and disassembly of microtubules. The calmodulin antagonists W-7 and W-5 suppressed nuclear migration. These results suggest that microtubules are essential for the migration and that nuclei are migrated via the Ca(2+)-induced, calmodulin mediated assembly and disassembly of the microtubule networks. Together, these results obtained with PKC activators/inhibitor, colchicine, and calmodulin antagonists suggest that nuclear migration is mediated by increases in PKC activity, requires intact microtubules, and is accompanied by PKC-dependent increases in cell-cell adhesion. PMID- 8449366 TI - Role of a gamete-specific sulfoglycolipid immobilizing protein on mouse sperm-egg binding. AB - A sulfoglycolipid immobilizing protein, termed SLIP1, is a conserved germ cell membrane protein that has been shown in vitro to bind specifically to the mammalian germ-cell-specific sulfoglycolipid, sulfogalactosylglycerolipid (SGG). SLIP1 was extracted from the mouse sperm surface by a sucrose/ATP/EDTA solution. Indirect immunofluorescence and immunoprotein A-gold labeling of live mouse sperm indicate that SLIP1 was present on the acrosomal plasma membrane. Inclusion of low concentrations of exogenous purified SLIP1 in the in vitro mouse sperm-egg binding assay culture significantly decreased the number of sperm bound per egg. Inhibition was heat labile. SLIP1 on sperm, rather than that on eggs, appeared to be important for the binding process since preexposure of sperm to anti-SLIP1 decreased sperm binding to the eggs. Eggs preincubated with anti-SLIP1 were unaffected. Immunoblotting studies confirmed that SLIP1 was not present on the zona pellucida (ZP). SLIP1 binding ligand(s) on eggs were also involved in sperm ZP binding since preincubation of eggs with exogenous SLIP1 before gamete coincubation significantly reduced the number of sperm bound per egg. The results suggest that SLIP1 is involved in mouse sperm-ZP binding. PMID- 8449367 TI - In vitro and in vivo expression of alpha 7 integrin and desmin define the primary and secondary myogenic lineages. AB - Skeletal muscle fibers form during two periods of development and differ biochemically, functionally and in their morphology. Primary fibers develop in the rat hindlimb during Days 14 to 16 of embryogenesis. These fibers are subsequently surrounded by secondary fibers that eventually constitute the bulk of muscle mass in the limbs. We have used the expression of the alpha 7 muscle laminin binding integrin (Song et al., J. Cell Biol. 117, 643-657, 1992) and the intermediate filament protein desmin to identify myogenic cells at distinct stages of development both in vitro and in vivo. The phenotypes of these cells, determined by immunofluorescence microscopy, discriminate two lineages and indicate that the development of primary and secondary muscle fibers is regulated by multiple mechanisms. The cells which compose the primary myogenic lineage are derived from a population of precursor cells that is in part present in the Day 12 embryo limb bud and which do not express either alpha 7 integrin or desmin. These precursor cells develop into cells that express desmin, but not alpha 7, and which subsequently mature into replicating myoblasts that are competent to undergo terminal differentiation. This maturation process requires the in vivo environment of the Day 13 embryo limb. The alpha 7 integrin and slow myosin heavy chain are first expressed in primary muscle cells well after the onset of terminal differentiation. Some cells that give rise to secondary muscle fibers also are present in the Day 12 embryo hindlimb. The precursors of secondary fibers will develop into cells which express either alpha 7 integrin or desmin and subsequently into replicating myoblasts that express both proteins. Upon terminal differentiation of secondary myoblasts there is an increase in the expression of both alpha 7 integrin and desmin. The temporal regulation of expression of these proteins indicates that the environment of the limb plays a role in the maturation of precursors of both lineages. At least two roles of alpha 7 integrin during myogenesis are related to its association with beta 1 integrin and its function as a laminin receptor. Laminin selectively maintains the proliferation of secondary myoblasts and modulates their shape and mobility in vitro. This responsiveness of secondary myoblasts to laminin corresponds to the time when laminin is a major component of the extracellular matrix, when there is an expansion of the population of secondary myoblasts, and when the alpha 7 integrin is expressed on secondary myoblasts in vivo.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8449368 TI - Structure/function analysis of the sea urchin sperm adhesive protein bindin. AB - The functional domain structure of bindin, an adhesive protein component of the acrosomal granule of sea urchin sperm, has been analyzed using a series of carboxyl- and amino-terminal deletion analogs of recombinant bindin expressed in Escherichia coli. Bindin, which self-associates to form macromolecular aggregates, mediates the species-specific attachment of sperm to the egg surface as well as egg-to-egg agglutination in vitro by binding to egg surface-sulfated fucose-containing glycoconjugates. Cross-species egg agglutination activity and sperm adhesion were determined for two sea urchin species, Strongylocentrotus purpuratus and S. franciscanus. We found that S. franciscanus sperm bindin agglutinates both S. franciscanus and S. purpuratus eggs whereas S. purpuratus sperm bindin displays a much more restricted specificity for homologous S. purpuratus eggs. Consistent with this result, cross-species sperm adhesion experiments demonstrate that S. franciscanus sperm also bind more efficiently to S. purpuratus eggs in comparison to S. purpuratus sperm attachment to S. franciscanus eggs. Recombinant S. purpuratus bindin demonstrates the same species specific egg agglutination properties observed for sperm bindin. Deletion mutants of S. purpuratus bindin were tested for their ability to species specifically agglutinate eggs. We found that residues 1-74 or residues 122-236 can be deleted without a loss of the species-specific agglutination properties of bindin. Comparison of the bindin amino acid sequences from the two species reveals that all of the active deletion analogs have a central segment in common corresponding to residues 75 through 121 of S. purpuratus bindin, where the sequences are identical except for a single amino acid, Arg 77, which is an Ala residue in S. franciscanus. However, substitution of Arg 77 for Ala does not alter the species specificity of recombinant bindin, suggesting that the more divergent amino- and carboxy-terminal sequences flanking the conserved central domain determine the species specificity of bindin and either end is sufficient to impart specificity. The amino- and carboxyl-terminal thirds of S. purpuratus bindin each contain two repeats of the sequence M G G P P/V. This sequence does not occur in S. franciscanus, which instead has five repeats of the sequence M G G A/V/Q F/V/P. It is conceivable that these repeats, which vary in sequence in bindins from different species, constitute an important part of the species recognition mechanism. PMID- 8449369 TI - A role for the WH-30 protein in sperm-sperm adhesion during rouleaux formation in the guinea pig. AB - Mammalian spermatozoa participate in specific cell adhesion phenomena during their development and functional lifespan; this includes interaction with Sertoli cells, the zona pellucida, and the oolemma. In some species such as the guinea pig, an additional sperm-sperm adhesion occurs during epididymal maturation which results in the formation of rouleaux in which the sperm heads are stacked one upon the other and the periacrosomal plasma membranes of adjacent sperm are linked by periodic cross-bridges. In this study, we have used a monoclonal antibody to investigate the role of the WH-30 protein on the sperm surface in the formation of the junctional zones between adjacent guinea pig sperm in rouleaux. WH-30 monoclonal antibodies caused a dose- and time-dependent dissociation of rouleaux and an increase in the percentage of single, acrosome-intact sperm; there were no effects on sperm motility (maintained at 80-90%) or ultrastructure during the 120-min incubations. The maximal effect of about 80% single sperm was obtained with a 1:4 dilution of the WH-30 hybridoma supernatant or 5-50 micrograms/ml of purified WH-30 IgG. In contrast, incubation of sperm in AH-20 IgG, myeloma cell supernatants, or purified, nonspecific mouse IgG1 had no effect on rouleaux. Treatment of sperm with a WH-30 Fab fragment resulted in almost complete dissociation of rouleaux without any observed effect on sperm motility or acrosomal status. Surface labeling of sperm followed by immunoprecipitation and SDS-PAGE revealed that the WH-30 antibody recognizes a single polypeptide of 43-45 kDa. Using immunofluorescence, the WH-30 protein was localized over the entire surface of the sperm head (whole-head pattern), and immunogold labeling showed that WH-30 is localized in the glycocalyx on both the dorsal and ventral surfaces of the periacrosomal and postacrosomal plasma membranes. These results indicate that the WH-30 protein on the sperm surface is a cell adhesion protein which is involved in the molecular interactions that maintain guinea pig sperm in rouleaux. PMID- 8449370 TI - Regional differences in troponin I isoform switching during rat heart development. AB - Expression of cardiac troponin I (TnIcardiac) and slow skeletal troponin I (TnIslow) genes was analyzed at the mRNA and protein level in the developing rat heart. TnIslow mRNA was detectable by in situ hybridization in the embryonic cardiac tube as early as the 13-somite stage (Embryonic Day 10). In contrast, TnIcardiac transcripts were first detected in the primordial atrium and ventricle of 11-day-old embryos, but were absent in the outflow tract region. TnIslow mRNA levels decreased after birth in atria and later in ventricles but persisted even in adult life in myocytes of the conduction system. TnIslow protein was detected by specific antibodies in atrial myocytes beginning from Embryonic Day 11; in contrast, ventricular myocytes were unreactive until Embryonic Day 18. Western blot analysis of 16-day-old fetal hearts confirmed the expression of TnIcardiac in atrial but not in ventricular myocardium. Slot blot analysis showed that at this stage equivalent amounts of TnIslow and TnIcardiac mRNAs are expressed in atria and ventricles. Similar differences in the expression of TnIslow and TnIcardiac mRNAs and proteins were observed in cultures of embryonic atrial and ventricular myocytes. The results suggest serial rather than simultaneous activation of TnIslow and TnIcardiac genes and they show that different regions of the developing heart differ in their patterns of TnIcardiac expression due to the operation of distinct mechanisms that separately affect the accumulation of TnIcardiac mRNA and protein. PMID- 8449371 TI - Morula decompaction (mdn), a preimplantation recessive lethal defect in a transgenic mouse line. AB - The beta S12 transgenic line carries an insertion of exogenous DNA and a deletion of approximately 2 cM on chromosome 1. Transgenic heterozygotes (beta S12/+) were viable and fertile, but homozygous mice (beta S12/beta S12) could not be produced. To determine the stage at which developmental arrest occurred in homozygotes, embryos derived from intercrosses among heterozygotes or from control crosses were examined at various stages. No homozygotes could be detected at postimplantation stages, suggesting that the mutation affected embryogenesis before implantation. Recovery of embryos at 1.5 or 3.5 days postcoitum, followed by culture in vitro, revealed an abnormal class of embryos which constituted one fourth of the progeny from intercrosses, and thus appeared to represent the beta S12/beta S12 homozygotes. These embryos cleaved normally to the 8-cell stage and formed compacted morulae, but then decompacted without forming a blastocyst, and ceased dividing at approximately the 16-cell stage. Nearly all blastomeres were viable at the time of decompaction, as demonstrated by trypan blue exclusion, indicating that the loss of compaction is not simply a consequence of cell death. When labeled with a short-term lineage marker and aggregated with normal embryos at the early 8-cell stage, homozygous mutant embryos failed to contribute to the resulting blastocysts, indicating that the defect in the maintenance of compaction is cell autonomous. Based on the mutant phenotype, we conclude that this genetic lesion affects a gene (or genes) required for the maintenance of compaction, and propose that it be named morula decompaction (mdn). The phenotype of mdn/mdn embryos appears to be distinct from those caused by other previously described preimplantation lethal mutations or chromosomal deletions. PMID- 8449372 TI - Upstream elements involved in the embryonic regulation of the sea urchin CyIIIb actin gene: temporal and spatial specific interactions at a single cis-acting element. AB - The sea urchin Strongylocentrotus purpuratus CyIIIb actin gene codes for a cytoskeletal type actin and is activated in the early embryo specifically in the cells destined to become the aboral ectoderm. Deletion constructs of its upstream region fused to the bacterial chloramphenicol acetyltransferase (CAT) gene were expressed in developing embryos following microinjection into eggs. These studies revealed the segments of the upstream region which are necessary for embryonic expression. We mapped the protein:DNA interaction sites in this upstream region by DNase I footprinting. At least five binding sites were identified in the 2173 nucleotide flanking sequence, which seem to include all the necessary elements for quantitative expression. One of these elements (E1) showed different patterns of association in vitro with nuclear proteins isolated from different stages in development. These different interactions are separated when nuclear extracts from ectodermal or endodermal-mesodermal tissues were used. When S. purpuratus eggs were injected with a CAT fusion construct mutated at this site, a decrease in CAT activity was observed only in late stage embryos (plutei), whereas early stage embryos (blastulae) exhibited wild-type CAT activity. These results suggest that the E1 element is involved in the temporal regulation of the CyIIIb gene. PMID- 8449373 TI - A theoretical and experimental examination of cell lineage relationships among cerebellar Purkinje cells in the mouse. AB - In this paper, we continue our examination of the role of cell lineage in the development of the cerebellar Purkinje cell population of the mouse. The analysis of Purkinje cell lineage is based on counts of the number of wild-type Purkinje cells in +/Lc<==>wild-type chimeras. +/Lc Purkinje cells undergo a cell autonomous degeneration early in postnatal development leaving variable numbers of wild-type Purkinje cells in chimeric animals. Using theoretical, statistical, and experimental approaches, we have tested various developmental models to account for the numerical development of Purkinje cell numbers in the +/Lc<==>wild-type chimeras. We have analyzed models based on the assumption that cell lineages are irrelevant to Purkinje cell development, as well as our own previous hypothesis that Purkinje cells descend from a small number of progenitor cells selected during the early stages of neurogenesis. The theoretical approach calculates the distributions of Purkinje cell numbers in hypothetical +/Lc<==>wild-type chimeras and inbred mice based on both clonal and nonclonal hypotheses of neuronal development. Variations of the model are compared with published cell counts from +/Lc<==>C3H/HeJ, +/Lc<==>C57BL/6J, +/Lc<==>AKR/J chimeras, and C3H/HeJ inbred mice. The statistical approach assesses the significance of the fits of the observed data with different variations of the model by Monte Carlo simulation techniques. The results of the comparison suggest that our observed data is more likely to be explained by a clonal model of development than by alternate models in which cell lineages play a minor role. Our experimental approach describes a new +/Lc<==>C3H/HeJ chimera in which all of the Purkinje cells (> 7900) are found on one side of the brain. We have analyzed this chimera with respect to clonal and nonclonal models of Purkinje cell development. The extreme asymmetric distribution of Purkinje cells provides added support to the hypothesis that there is a small number of progenitor cells that generate Purkinje cells. Our findings lead to the conclusion that while not all alternate models of mammalian CNS development can be completely excluded, the early progenitor hypothesis is the most probable model of Purkinje cell development. PMID- 8449374 TI - Protein kinase C, a pivotal regulator of hamster egg activation, functions after elevation of intracellular free calcium. AB - We investigated the signal transduction pathways that mediate activation of Syrian hamster eggs. Under conditions in which the concentration of intracellular free calcium ([Ca2+]i) is clamped low, activation of protein kinase C (PKC) can induce second polar body formation, reformation of the nuclear envelope, and decondensation of chromatin, as well as golgi reformation. However, calcium is necessary for normal transition from meiotic metaphase II to anaphase II. Conversely, under conditions in which the level of PKC activity is clamped low, induction of a rise in [Ca2+]i, using the calcium ionophore A23187, does not induce egg activation. These results strongly suggest that PKC acts after the calcium signal as a proximal inducer of egg activation. This suggestion is supported by the kinetics of egg activation; PKC stimulators activate the eggs at a significantly enhanced rate (P < 0.01) compared with activation by calcium ionophore. We show here that PKC stimulators induce emission of the second polar body, but that subsequently, with longer culture, the emitted polar body is absorbed. Our results suggest that the rise in [Ca2+]i serves two functions, to activate PKC and to induce the transition from metaphase II to anaphase II. PKC, once activated, mediates several other events of egg activation. PMID- 8449375 TI - Effects of inhibitory casts and orthoses on bony alignment of foot and ankle during weight-bearing in children with spasticity. AB - One theory about the improvements in gait seen in children with CP who use inhibitory casts holds that they are a result of better posture of the foot. To examine this theory, the authors used x-rays to document the position of the foot both before and during inhibitory casting to see whether there were measurable changes in foot posture that could be ascribed to the casts. The bony alignment of the ankle and foot was compared during weight-bearing with the children in and out of inhibitory casts (N = 12), static ankle-foot orthoses (N = 7) and articulated ankle-foot orthoses (N = 8). The only angle change which was significant was calcaneal inclination in the articulated AFOs versus out of the orthoses. There was no significant difference in any of the other angles in any of the groups. PMID- 8449376 TI - Muscle performance and gross motor function of children with spastic cerebral palsy. AB - The purpose of this study was to determine whether, and to what extent, performance on a measure of motor function (Gross Motor Function Measure, GMFM) was related to the physiological fitness of children with cerebral palsy (CP). Two elements of physiological function were measured: aerobic power and anaerobic power of the arms and legs. 15 boys and eight girls aged between seven and 13.9 years with spastic CP participated in the study. There was a good relationship between the standing and walking, running and jumping sub-sections and the total score of the GMFM on one hand, and anaerobic capacity of the legs on the other. However, the relationships for the arms were limited, indicating that the GMFM is not a suitable tool for providing information about aerobic fitness in children with CP, or about anaerobic power of the arms. PMID- 8449377 TI - Parents caring for young adults with severe physical disabilities: psychological issues. AB - The authors studied the psychological aspects for parents of caring for a young adult with severe physical disabilities. Mothers reported significantly more caregiving stress than fathers; a major factor was the persistent limitations in their personal life opportunities and choices at a time when most parents experience freedom from caregiving responsibilities. Contrary to the assumptions of health-care professionals, the parents indicated that they were more anxious than depressed about their future options and their child's quality of care and future living circumstances. There was no major psychopathology and a review of high scores on the scale of Psychoticism and Paranoia indicated that the parents' responses were a reflection of realistic isolation and lack of trust in professional and agency-based relationships. PMID- 8449379 TI - Evoked potentials in infant brainstem syndrome associated with Arnold-Chiari malformation. AB - This study evaluated the contribution of brainstem auditory evoked potentials (BAEPs) and median nerve somatosensory evoked potentials (SEPs) to the assessment of brainstem dysfunction in infants with myelomeningocele and Arnold-Chiari malformation. 16 infants under one year of age were studied. Six had infant brainstem syndrome (IBS). 11 had abnormally prolonged I-V interwave latency (brainstem transmission time, BSTT); BSTT did not differentiate those patients with and without IBS. The cortical 'N20' component of the median-nerve SEPs was absent or had low amplitude and prolonged latency in all six patients with clinical signs of brainstem dysfunction and in four without. Median-nerve SEPs were normal in the patients without IBS. There was a significant difference between patients with and without IBS. Median-nerve SEPs may be a helpful measure of brainstem function in infants with Arnold-Chiari malformation. PMID- 8449378 TI - Hypoxemia during oral feeding of children with severe cerebral palsy. AB - Oral feeding of children with severe dysphagia and multiple disabilities may result in hypoxemia. Pulse oximetry was used to monitor hemoglobin saturation (SpO2) during oral feeding of five children with multiple disabilities who were referred because of food refusal or coughing and fatigue during feeding. Modified barium videofluoroscopic swallow studies demonstrated deglutition abnormalities. SpO2 values were within the normal range at rest, but routine, upright oral feeding resulted in significant degrees of hypoxemia. The pharyngeal stage of deglutition was abnormal in all five children. In three, the periods of hypoxemia were dependent on food texture. Awareness of meal-time hypoxemia contributed to the decision to use gastrostomy-tube feedings for the other two children. Pulse oximetry during oral feeding should be considered for all children with severe dysphagia and multiple disabilities. PMID- 8449380 TI - EEGs in phenylketonuria. I: Follow-up to adulthood; II: Short-term diet-related changes in EEGs and cognitive function. AB - The authors report the results of two EEG studies on adult patients with phenylketonuria (PKU) who had been treated early. Part I: the authors followed the EEGs of 34 PKU patients from birth to age 21. The frequency of abnormal EEG findings (especially epileptiform activity) steadily increased until age 12, then decreased. IQ correlated significantly with quality of dietary control during follow-up. Part II: frequency analysis of the EEG and neuropsychological testing were performed on eight adult patients after periods of four weeks with low and high levels of phenylalanine. Only five patients followed the strict dietary regulations. With high levels of phenylalanine, the dominant peak of EEG background activity shifted to the slower frequency spectrum in all patients; in addition, neuropsychological testing revealed impairment of cognitive function. The significance of different approaches of EEG examinations is discussed with respect to the problems of monitoring PKU patients and the pathogenic mechanisms of CNS damage in phenylketonuria. PMID- 8449381 TI - Tactile naming disorder of the left hand in two cases with corpus callosum agenesis. AB - The authors report two girls with corpus callosum agenesis, with unilateral tactile naming disorder in the left hand. Neuropsychological examinations were performed and tactile perception and naming were studied. The results suggested that tactile naming disorder in both cases could be regarded as a disconnection deficit. Both had daily epileptic attacks and mild or moderate mental deficiency. In these severely impaired children, brain capacity and neural plasticity seem inferior, so classical disconnection deficits might be demonstrated. PMID- 8449382 TI - Cor pulmonale as a complication of ventriculo-atrial shunts reviewed. AB - The authors present the case of a nine-year-old patient with spina bifida and hydrocephalus treated with a ventriculo-atrial shunt who developed fatal pulmonary hypertension 5 1/2 years after his last valve revision; he had been well and active up to one month before his death. Details of the dramatic cardiovascular findings are given. The problems of treatment, once symptoms occur, and the difficulty of pre-symptomatic detection are discussed. PMID- 8449383 TI - Hunter syndrome: cloning of the gene, mutations and carrier detection. PMID- 8449384 TI - Heinz body hemolytic anemia induced by DQ-2511, a new anti-ulcer drug, in dogs. AB - DQ-2511, a new anti-ulcer drug, was administered to beagle dogs for 4 weeks to investigate the mechanism whereby this drug induced hemolytic anemia and its reversibility in comparison with beta-acetylphenylhydrazine. Hemolytic anemia accompanied by an increase in the number of cells containing Heinz bodies that was preceded by a marked decrease in blood-reduced glutathione concentration was observed in dogs receiving 600 mg/kg of DQ-2511, but only a slight increase in the methemoglobin level was noted. beta-Acetylphenylhydrazine, however, caused hemolytic anemia accompanied by marked increases in both Heinz body-containing cells and methemoglobin concentration, but the blood-reduced glutathione concentration was not decreased consistently with the formation of Heinz bodies. Hemolytic anemia disappeared after a 4-week recovery period in the dogs that received DQ-2511. These results suggest that decreases in reduced glutathione in erythrocytes play an important role in the anemia and Heinz body formation induced by DQ-2511, but not by beta-acetylphenylhydrazine. PMID- 8449385 TI - Chronic (1-year) safety evaluation of ipazilide fumarate, an antiarrhythmic agent, administered orally to rats. AB - Ipazilide fumarate (WIN 54177-4) is a chemically novel antiarrhythmic agent that prolongs ventricular refractoriness and possesses antiectopic activity. The compound is being developed as oral and iv therapy for ventricular and supraventricular arrhythmias. Since ipazilide therapy may require long-term use, a 1-year oral gavage study (daily dosages of 20, 80, or 160 mg/kg) was conducted in rats. Controls received the purified water vehicle. Treatment-related clinical signs were limited to post-dosing salivation. Increased relative liver weight (females, at 80 and 160 mg/kg) was correlated with centrilobular hypertrophy, but was not associated with significant increased serum liver enzymes activities. These liver weight changes were interpreted as an adaptive metabolic response and were not considered toxicologically significant. An increased incidence of centrilobular hepatocellular vacuolation representing lipid accumulation over that observed for male controls occurred for males in all ipazilide-treated groups. This observation, however, was not correlated with elevated hepatic enzyme activities. Hepatocellular basophilic foci were observed for females only (80 and 160 mg/kg groups); however, the significance of this lesion is unclear. Transient dosage-related duodenal villous atrophy/sloughing was observed for males from the 80 and 160 mg/kg groups. Mild increases in hemoglobin, hematocrit, urea, and creatinine (160 mg/kg), attributed to treatment, were considered of minor toxicologic importance. Likewise, no clinical or anatomical pathologic observations that may indicate cardiac toxicity were determined. It is concluded that a dosage of 20 mg/kg (two to three times the clinical efficacious dosage) was considered a no-effect dosage level since it did not produce any effects of toxicological significance. PMID- 8449386 TI - Relationship between hepatocyte necrosis, proliferation, and initiation induced by diethylnitrosamine in the male F344 rat. AB - Diethylnitrosamine (DEN) is commonly used as an initiator in rodent models of multistage carcinogenesis. Because the initiating activity of DEN has been attributed, in part, to its induction of regenerative cell proliferation, the temporal and quantitative relationships among necrosis, replication, and initiation were characterized in livers of male F344 rats subsequent to administration of a single dose of 10 or 150 mg DEN/kg. Following a dose of 150 mg DEN/kg body weight, maximal hepatocellular necrosis was observed 2 days postinjection and amounted to 9% of the hepatic volume being necrotic by light microscopic criteria. Changes in serum levels of alanine and aspartate aminotransferases, indicators of hepatocellular necrosis, paralleled changes in the necrotic volume fraction. Hepatocyte replication was estimated using nuclear labeling with bromodeoxyuridine (BrdU), which was constantly infused for 2 or 7 days by osmotic minipump. BrdU labeling was maximally increased at 4 days with 2 day infusion (26.1% in treated vs 0.5% in controls) and at 7 days with 7-day infusion (46% in treated vs 2% in controls). Initiation was quantitated by enumeration of hepatocytes which stained positive for placental glutathione-S transferase (GST-P). Increased numbers of GST-P-positive hepatocytes were observed on Day 4 and increased to a maximum of 109/cm2 section area, or 0.077% of all hepatocytes. Thus, the temporal pattern changes following 150 mg DEN/kg body wt are consistent with the attribution of regenerative cell proliferation contributing to the yield of initiated cells. A comparison of the peak BrdU (2 day) labeling index and the peak GST-P staining frequency suggests a rate of initiation of roughly 10(-3)-10(-4)/cell division following 150 mg DEN/kg body wt.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8449387 TI - Characterization of disulfoton-induced behavioral and neurochemical effects following repeated exposure. AB - These experiments examined the relationship between behavioral alterations and neurochemical changes in rats exposed repeatedly to disulfoton, an organophosphate cholinesterase inhibitor. Male Long-Evans rats were injected ip for 30 days with 0, 0.5, 1, or 2 mg/kg of disulfoton in corn oil. Clinical signs and motor activity were measured during the course of repeated exposure. Cognitive function, as measured in the Morris water maze, and passive avoidance procedures were assessed near the end of the dosing regimen. Regional brain acetylcholinesterase (AChE) activity was measured during the course of dosing while the total number of muscarinic receptors was measured at the end of the dosing regimen. Tolerance developed rapidly to the clinical signs produced by disulfoton, but not to the disulfoton-induced decrease in motor activity. Disulfoton affected the acquisition of water maze performance, but had no effect on passive avoidance acquisition or retention. Repeated exposure to disulfoton decreased brain AChE activity and the number of [3H]quinuclidinyl benzilate binding sites. These data indicate that, in spite of muscarinic receptor down regulation that followed repeated exposure to disulfoton, animals become tolerant to only some of the functional effects produced by this chemical. PMID- 8449389 TI - The effects of prenatal administration of azo dyes on testicular development in the mouse: a structure activity profile of dyes derived from benzidine, dimethylbenzidine, or dimethoxybenzidine. AB - In mice and rats, prenatal exposure to the dye Congo red permanently reduces the number of germ cells in male and female offspring. In the current investigation, nine other dyes structurally related to Congo red were examined for developmental testicular toxicity. In this study, the structural component of the dyes responsible for the prenatal induction of germ cell aplasia was identified. We found that only benzidine-based dyes altered testicular development and caused hypospermatogenesis in mice during adulthood. Dimethyl- and dimethoxybenzidine based dyes were without effect. Pregnant mice were dosed orally on Days 8-12 of gestation with a benzidine-, dimethylbenzidine-, or a dimethoxybenzidine-based dye and the testes of 45- to 50-day-old male offspring were examined. The testes of postpubertal male offspring exposed to the benzidine-based dyes, Congo red, diamine blue, and Chlorazol Black E, were small and contained some tubules completely devoid of germ cells, but the dimethylbenzidine-based dyes, trypan blue, Evans blue, and benzopurpurin 4B, and the dimethoxybenzidine-based dye, Chicago sky blue, did not alter testicular development in this manner. Azoic diazo component 48, a dimethoxybenzidine congener, and two other diazo dyes, naphthol blue black and Sudan III, were also without effect on the germ cells. Experiments with Chlorazol Black E (CBE) indicate that the period of susceptibility in the male fetus is limited to the period of primordial germ cell migration and division. When CBE was administered on Days 8-10 of gestation it reduced testis weight after puberty by 30%, while treatment after Day 13 did not affect testicular function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8449388 TI - A novel system for the in vitro exposure of pulmonary cells to acid sulfate aerosols. AB - While ambient acid aerosols are considered a potential respiratory health hazard, the mechanism by which they induce responses in the lungs is not known. Attempts to ascertain these mechanisms using inhalation exposures are complicated by a number of technical difficulties, chief among which are neutralization of inhaled acids by endogenous ammonia and variations in deposition with inhaled particle size. To control for these variables, a novel in vitro exposure system allowing experimental evaluation of factors which influence biologic responses to acid sulfate particles was developed. The system consists of two subunits, a generation/delivery component and a cell exposure component. Sulfuric acid aerosols are generated by nebulizing dilute acid solutions. Particles larger than a specified size of interest (based upon the specific exposure conditions desired) are removed, and particles at the desired size and mass concentration are uniformly delivered onto a target cell monolayer. The system is capable of delivering acid particles larger than 0.7 micron (mass median diameter), yet at constant particle mass concentrations. This paper describes the design of the exposure system and its performance characteristics and presents initial results of some biological responses obtained using it. In conjunction with inhalation studies, this exposure system may provide additional insights into mechanisms by which acid aerosols adversely affect the respiratory tract and into the physical characteristics of acid particles which modulate toxicity. PMID- 8449390 TI - Induction of metallothionein by arsenicals in mice. AB - Metallothionein (MT) is a sulfhydryl-rich, metal-binding protein that provides protection against metal toxicity. MT is induced by acute stress, hormones, metals, and various organic compounds. Recently, arsenicals have also been shown to induce MT. However, the mechanism and character of MT induction by arsenicals is unknown. Therefore, the effect of various arsenic forms on the tissue concentration of MT was determined. Mice were injected sc with various doses of arsenite [As(III)], arsenate [As(V)], monomethylarsenate (MMAA), and dimethylarsenate (DMAA), and MT content in the liver was measured 24 hr later by the Cd-hemoglobin radioassay. As(III) is a potent hepatic MT inducer in that a 30 fold increase in MT was observed at the dose of 85 mumol/kg. In comparison, it took 3-, 50-, and 120-fold higher molar amounts of As(V), MMAA, and DMAA, respectively to produce a similar effect. MMAA produces the largest increase in hepatic MT (80-fold), followed by As(III) (30-fold), As(V) (25-fold), and DMAA (10-fold). However, none of the arsenicals induced MT in mouse primary hepatocyte cultures. Both MT-I and MT-II were coordinately induced by As(III), As(V), and MMAA. MT induction by As(III) was further characterized following sc administration of arsenite (85 mumol/kg). Hepatic MT induction peaked at 24 hr, and in addition to the liver, As(III) also increased MT in kidney, spleen, stomach, intestine, heart, and lung. MT-I mRNA increased 24-, 52-, and 11-fold at 3, 6, and 15 hr after As(III) administration. This induction profile is similar to that observed after Zn or Cd exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8449391 TI - In vivo microdialysis sampling of phenol and phenyl glucuronide in the blood of unanesthetized rainbow trout: implications for toxicokinetic studies. AB - Microdialysis (MD) is a sampling method that allows continuous in vivo collection of free, unbound chemicals in blood and interstitial fluids. In the present study we describe a surgical method for placement of a MD probe in the dorsal aorta of 600- to 900-g rainbow trout (Onchorhynchus mykiss). A specially designed probe guide was inserted into the dorsal aorta via the mouth. A PE-50 polyethylene cannula was then inserted into the probe guide and used to further position and maintain the probe guide in the dorsal aorta. Once proper placement of the probe guide was ascertained, the cannula was removed and a CMA-10 MD probe (4-mm tip) was inserted. The animal was then placed into a respirometer-metabolism chamber and allowed to recover from anesthesia. The placement and functionality of the probe were evaluated by examining the in vivo toxicokinetics of phenol (PH) and phenyl glucuronide (PG) in the blood of an unanesthetized rainbow trout exposed to water-borne PH (7.0 mg/liter). Prior to and following the introduction of PH into the metabolism chamber, MD samples (150 microliters) were collected at 30 min intervals and analyzed for free plasma PH and PG by HPLC. Total PH in exposure water and blood was also monitored every 30 min. Free PH and total PH in plasma accumulated rapidly and reached apparent steady-state levels of 54 and 142 pmol/microliters, respectively, in about 60 min. A blood:water partition coefficient of 2.0-2.6 was determined from these data, while bound and free plasma PH were 60 and 40%, respectively. PG was not detected until approximately 90 min of PH exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8449392 TI - Assessment of the developmental toxicity of 2-ethylhexanoic acid in rats and rabbits. AB - This study was carried out to assess the developmental toxicity of orally administered 2-ethylhexanoic acid (2-EHA) throughout organogenesis in the rat and the rabbit. Treatment of Fischer 344 inbred rats with doses of 100 to 1000 mg 2 EHA/kg/day on (Gestation Days) (GD) 6-15 in a range-finding and a definitive study resulted in a high level of maternal death at 1000 mg/kg/day. Clinical signs of maternal toxicity, including increased liver weight, as well as increased resorptions, dead fetuses, and growth retardation, but no malformations, were observed at 500 mg/kg/day. Slight developmental toxicity, manifested as a reduction in skeletal ossification, occurred in fetuses exposed to 250 mg/kg/day. No adverse effects of treatment were associated with the lower 2-EHA doses (100 and 125 mg/kg/day). Maternal toxicity was also observed in range finding and definitive studies in New Zealand white rabbits exposed to 25 to 1000 mg 2-EHA/kg/day on GD 6-18 with excessive mortality observed at the highest doses (500 and 1000 mg/kg/day). A low incidence of maternal death as well as abortion occurred following treatment with 125 and 250 mg 2-EHA/kg/day. Less severe clinical signs (reduced weight and food consumption and hypoactivity) were also observed in the 250 mg/kg/day group. There were no adverse effects on fetal viability, growth, or morphology at any dose level. Thus, exposure to 2-EHA during the entire period of organogenesis caused developmental toxicity only at maternally toxic doses in the rat or adverse maternal effects in the absence of developmental toxicity in the rabbit. No evidence of teratogenicity was associated with 2-EHA in this classical safety assessment regimen in either species. The no observed adverse effect levels (NOAELs) for maternal and developmental toxicities in rats are 250 and 100 mg/kg/day, respectively; the corresponding NOAELs for rabbits are 25 mg/kg/day (maternal) and > or = 250 mg/kg/day (developmental). PMID- 8449393 TI - Modulation of muscarinic receptors and acetylcholinesterase activity in lymphocytes and in brain areas following repeated organophosphate exposure in rats. AB - Repeated exposures to organophosphorus (OP) insecticides has been shown to cause a decrease of cholinergic muscarinic receptors (mAChR) in brain and in peripheral tissues. These changes are believed to be involved in the development of tolerance to OP toxicity and may play a role in cognitive dysfunctions observed following repeated OP exposure. Recently, mAChRs identified in circulating lymphocytes have been shown to be modulated similarly to brain mAChRs following repeated OP exposure, suggesting that these peripheral cells may be useful as indicators of mAChR changes in the central nervous system. This study was designed to further investigate whether mAChRs on lymphocytes could serve as a biomarker for changes in brain mAChRs during prolonged OP exposure and during recovery from such exposure. Using the mAChR antagonist [3H]quinuclidinyl benzilate (QNB) to label mAChRs, we found that exposure to disulfoton for 14 days (2 mg/kg/day by gavage) caused a significant decrease (25-35%) in muscarinic receptors density in the cerebral cortex, hippocampus, and striatum, as well as in circulating lymphocytes. The decline of mAChR density in lymphocytes paralleled those observed in brain, particularly in cortex and hippocampus, during exposure to disulfoton; however, while brain mAChR levels recovered slowly after termination of exposure and remained significantly reduced 4 weeks after the last treatment, [3H]QNB binding in lymphocytes recovered rapidly within 1 week. Similarly, lymphocyte acetylcholinesterase (AChE) activity was significantly inhibited and correlated well with brain AChE activity during exposure, but the recovery was rapid relative to AChE activity in brain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8449394 TI - Developmental toxicity of inhaled trans-1,2-dichloroethylene in the rat. AB - The developmental toxicity of trans-1,2-dichloroethylene (t-DCE), a component of certain Freon cleaning agents, was examined in pregnant rats. t-DCE was administered by inhalation 6 hr daily on Days 7-16 of gestation (the day copulation was confirmed was termed Day 1 of gestation) at exposure levels of 0, 2000, 6000, or 12,000 ppm. The offspring were then examined on Day 22 of gestation. Overt maternal toxicity was expressed as a significant reduction in weight gain at 12,000 ppm and in feed consumption at 6000 and 12,000 ppm. During the exposure period, lacrimation and stained periocular hair, and signs of ocular irritation, were observed in all groups. In addition, increased incidences of alopecia, lethargy, and salivation were observed in the high-dose dams. Significant increases in the mean number of resorptions per litter were seen in the litters of dams exposed to 6000 and 12,000 ppm of t-DCE; however, these values are within the range of historical controls and not considered to be treatment related. The mean combined and female fetal weights were significantly reduced in the litters of dams exposed to the highest concentration (12,000 ppm) of t-DCE. Marginal effects on feed consumption, unaccompanied by other changes and reflective of the pattern seen at higher doses, were seen at 2000 ppm. Thus, marginal maternal toxicity was seen at 2000 ppm and exposures to 6000 ppm t-DCE or higher caused frank maternal toxicity while the fetus was affected only at 12,000 ppm. Therefore, t-DCE is not considered to be uniquely toxic to the rat conceptus. PMID- 8449395 TI - Toxicokinetics of inhaled bromotrifluoromethane (Halon 1301) in human subjects. AB - Bromotrifluoromethane (CBrF3), commonly known as Halon 1301, is used as a fire extinguishant in the Space Shuttle. Several scenarios, such as a fire or a faulty alarm, could lead to its discharge resulting in a Halon 1301 concentration of up to 1% in the spacecraft cabin atmosphere. To examine the effects of Halon 1301 on mental performance and physiologic function, the National Aeronautics and Space Administration sponsored a human inhalation study. Four pairs of adult male subjects were each exposed in a double-blind fashion for 24 hr to 1% (10,000 ppm or 60,875 mg/m3) Halon 1301 and to air in two separate exposures approximately 1 week apart. Mental performance and physiologic function were assessed and the results are reported in a companion paper (D. S. Calkins, J. J. Degioanni, M. N. Tan, J. R. Davis, and D. L. Pierson. Fundam. Appl. Toxicol. 20, in press). Blood and breath samples from the exposed subjects were also collected to provide dosimetric and toxicokinetic information, which is presented here. Blood Halon 1301 levels increased rapidly and approached a steady state within 2 hr of beginning the exposure; the steady-state concentration was approximately 3-4.5 micrograms/ml. Breath samples collected during exposures closely reflected chamber concentrations. Analysis of postexposure blood samples revealed that Halon 1301 was eliminated biphasically with an average t1/2 alpha and t1/2 beta of 4.5 min (range 2.5-8.1 min) and 200 min (range 131-347 min), respectively. Halon 1301 concentrations in fat and soft tissues were also estimated. Subsequently, the end-tidal breath/blood/tissue/fat partition coefficients were calculated to be 17/1/0.5/33.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8449396 TI - Human performance and physiological function during a 24-hr exposure to 1% bromotrifluoromethane (Halon 1301). AB - Performance and physiological measurements were obtained from four pairs of men exposed for 24 hr to 1% (10,000 ppm) Halon 1301 (bromotrifluoromethane, CBrF3) and to air with order counterbalanced using a double-blind protocol. Cognitive and motor performance was assessed before, during, and after the exposures using seven scales of the Automated Portable Testing System, which produced 13 measures of performance. Halon inhalation induced decrements in 2 of the 13 measures, but actual and estimated magnitudes of the decrements were no greater than 5% of baseline values. Physiological data were obtained before, during, and after the exposures from clinical chemistry analyses of blood and urine samples, pulmonary function tests, and monitoring of vital signs. Significant change during Halon inhalation was observed for 6 of the 52 variables assessed; however, all physiological values remained within clinically acceptable limits. No cardiovascular effects were noted. This study demonstrated that exposure to 1% Halon 1301 for 24 hr can produce minor disturbance of central nervous system function as assessed by cognitive tasks. PMID- 8449397 TI - Developmental toxicity of acrolein in New Zealand white rabbits. AB - Pregnant New Zealand white rabbits (20 per group) were treated via stomach tube with 0.0, 0.1, 0.75, or 2.0 mg/kg/day from Days 7 through 19 of presumed gestation and subjected to cesarean sectioning on Day 29. Throughout the period of treatment, clinical observations, feed consumption, and body weights were recorded. At the termination of the study, reproductive and fetal parameters were measured. Three does died during the study, and transient effects on body weight gains and feed consumption were noted, with a subsequent rebound effect reflected in both fetal and maternal weights in the high-dose group (2 mg/kg/day). Resorptions were elevated in the high-dose group, but the effect was not statistically significant. Fetal malformations were distributed evenly among groups, and incidences were consistent with historical control data on the same strain and at the same laboratory. Higher dosage levels (range-finding study, 4.0 and 6.0 mg/kg/day) produced high incidences of maternal mortality, spontaneous abortion, resorptions, clinical signs, gastric ulceration, and/or sloughing of the gastric mucosa. Acrolein was not found to be a developmental toxicant or teratogen at doses not toxic to the does under the conditions employed in this study. PMID- 8449398 TI - Effects of difloxacin on the metabolism of glycosaminoglycans and collagen in organ cultures of articular cartilage. AB - Fluoroquinolones, including difloxacin, are potent antibacterial compounds which, as a side effect, cause lesions in articular-epiphyseal cartilage complexes (AECC) of growing animals. To evaluate the effects of difloxacin on the structure of AECC and the metabolism of sulfated glycosaminoglycans (GAG) and collagen, explants of AECC were obtained from 18 healthy, 3-month-old Beagle dogs and cultured in medium which either had no difloxacin or had the drug at one of three concentrations (40, 80, or 160 micrograms/ml). Rates of synthesis of GAG and collagen were reduced by concentrations of difloxacin that were at or above 80 micrograms/ml. The rate of synthesis of total protein, however, was reduced only at the highest dose level. Catabolism of GAG and collagen was unaffected by the treatment. The principal ultrastructural changes in affected chondrocytes were distension of rough endoplasmic reticulum with electron-dense material that was probably protein, and vacuolation of cytoplasm. Structural changes were not observed in the extracellular matrix. It, therefore, appeared plausible that difloxacin affected chondrocytes by interfering with secretion of the matrix components, GAG and collagen. PMID- 8449399 TI - Direct binding of cyclin D to the retinoblastoma gene product (pRb) and pRb phosphorylation by the cyclin D-dependent kinase CDK4. AB - The product (pRb) of the retinoblastoma gene (RB-1) prevents S-phase entry during the cell cycle, and inactivation of this growth-suppressive function is presumed to result from pRb hyperphosphorylation during late G1 phase. Complexes of the cyclin-dependent kinase, cdk4, and each of three different D-type cyclins, assembled in insect Sf9 cells, phosphorylated a pRb fusion protein in vitro at sites identical to those phosphorylated in human T cells. Only D-type cyclins activated cdk4 enzyme activity, whereas cyclins A, B1, and E did not. When Sf9 cells were coinfected with baculovirus vectors encoding human pRb and murine D type cyclins, cyclins D2 and D3, but not D1, bound pRb with high stoichiometry in intact cells. Introduction of a vector encoding cdk4, together with those expressing pRb and D-type cyclins, induced pRb hyperphosphorylation and dissociation of cyclins D2 and D3, whereas expression of a kinase-defective cdk4 mutant in lieu of the wild-type catalytic subunit yielded ternary complexes. The transcription factor E2F-1 also bound to pRb in insect cells, and coexpression of cyclin D-cdk4 complexes, but neither subunit alone, triggered pRb phosphorylation and prevented its interaction with E2F-1. The D-type cyclins may play dual roles as cdk4 regulatory subunits and as adaptor proteins that physically target active enzyme complexes to particular substrates. PMID- 8449400 TI - The HAT4 gene of Arabidopsis encodes a developmental regulator. AB - The HAT4 gene from the plant Arabidopsis thaliana encodes a homeo domain protein that contains a leucine zipper motif. Homeo domain-leucine zipper (HD-Zip) proteins have not been found in animal systems, suggesting that HAT4 may define a new family of transcription factors that regulate higher plant development. To explore this possibility, functional studies of HAT4 were carried out in yeast and in transgenic plants. Point mutants of HAT4 isolated in yeast define functionally critical residues within the HD-Zip domain, many of which correspond to highly conserved positions in known homeo domains and leucine zippers. Transgenic plants bearing constructs that alter HAT4 expression exhibit a series of interesting developmental phenotypes, including changes in morphology and developmental rate. Thus, the HAT4 gene of Arabidopsis encodes an HD-Zip protein that functions as a novel developmental regulator. PMID- 8449401 TI - Cloning and characterization of PSF, a novel pre-mRNA splicing factor. AB - Previously, we characterized cDNAs encoding polypyrimidine tract-binding protein (PTB) and showed that a complex between PTB and a 100-kD protein was necessary for pre-mRNA splicing. In this paper we have used two different in vitro-binding assays to confirm and extend the interaction between these two proteins. Peptide sequence information was used to clone and sequence cDNAs encoding alternatively spliced forms of the 100-kD protein. It contains two consensus RNA-binding domains and an unusual amino terminus rich in proline and glutamine residues. The protein is highly basic and migrates anomalously on SDS gels. Owing to its interaction with PTB and its role in pre-mRNA splicing, we have termed the 100-kD protein PTB-associated splicing factor (PSF). The RNA-binding properties of PSF are apparently identical to those of PTB. Both proteins, together and independently, bind the polypyrimidine tract of mammalian introns. Biochemical complementation, antibody inhibition, and immunodepletion experiments demonstrate that PSF is an essential pre-mRNA splicing factor required early in spliceosome formation. Bacterially synthesized PSF is able to complement immunodepleted extracts and restore splicing activity. Despite association with PSF, complementary experiments with antibodies against PTB do not suggest an essential role for PTB in pre-mRNA splicing. PMID- 8449402 TI - The role of exon sequences in splice site selection. AB - Using mouse immunoglobulin mu (IgM) pre-mRNA as the model substrate for in vitro splicing, we have explored the role of exon sequences in splicing. We have found that deletion of the 5' portion of exon M2 of the IgM gene abolishes the splicing of its immediately upstream intron. Splicing was restored when a purine-rich sequence found within the deleted region was reinserted into the deletion construct. This M2 exon sequence was able to stimulate the splicing of a heterologous intron of the Drosophila doublesex pre-mRNA that contains a suboptimal 3' splice site sequence. These results show that the IgM M2 exon sequence functions as a splicing enhancer. We found that the assembly of the early splicing complex is stimulated by the M2 exon sequence. In vitro competition experiments show that this stimulatory effect is mediated by the interaction of some trans-acting factors. Our results suggest that the U1 snRNP is one such factor. We propose that recognition of an enhancer exon sequence by the components of splicing machinery plays a vital role in the selection of splice sites, not only for the IgM pre-mRNA but for other pre-mRNAs. We designate such a sequence as exon recognition sequence (ERS). PMID- 8449403 TI - An enhancer screen identifies a gene that encodes the yeast U1 snRNP A protein: implications for snRNP protein function in pre-mRNA splicing. AB - In an enhancer screen for yeast mutants that may interact with U1 small nuclear RNA (snRNA), we identified a gene that encodes the apparent yeast homolog of the well-studied human U1A protein. Both in vitro and in vivo, the absence of the protein has a dramatic effect on the activity of U1 snRNP containing the mutant U1 snRNA used in the screen. Surprisingly, the U1A gene is inessential in a wild type U1 RNA background, as growth rate and the splicing of endogenous pre-mRNA transcripts are normal in these strains that lack the U1A protein. Even in vitro, the absence of the protein has little effect on splicing. On the basis of these observations, we suggest that a principal role of the U1A protein is to help fold or maintain U1 RNA in an active configuration. PMID- 8449404 TI - Cloning of the mouse agouti gene predicts a secreted protein ubiquitously expressed in mice carrying the lethal yellow mutation. AB - The mouse agouti gene controls the deposition of yellow and black pigment in developing hairs. Several dominant alleles, including lethal yellow (Ay), result in the exclusive production of yellow pigment and have pleiotropic effects that include obesity and increased tumor susceptibility. In an interspecific backcross, we established genetic limits for the agouti gene and found that the Ay and the lethal non-agouti (ax) allele were not separated from a previously identified probe at the breakpoint of the Is1GsO chromosomal rearrangement. Using the Is1GsO probe, we isolated the agouti gene, and find that it has the potential to code for a secreted protein expressed in hair follicles and the epidermis, and that the level of expression correlates with the synthesis of yellow pigment. In the Ay mutation, there is a chromosomal rearrangement that results in the production of a chimeric RNA expressed in nearly every tissue of the body. The 5' portion of this chimeric RNA contains highly expressed novel 5' sequences, but the 3' portion retains the protein-coding potential of the nonmutant allele. We speculate that dominant pleiotropic effects of Ay are caused by ectopic activation of a signaling pathway similar to that used during normal hair growth. PMID- 8449405 TI - Expression of the developmental I antigen by a cloned human cDNA encoding a member of a beta-1,6-N-acetylglucosaminyltransferase gene family. AB - The blood group i/I antigens were the first identified alloantigens that display a dramatic change during human development. The i and I antigens are determined by linear and branched poly-N-acetyllactosaminoglycans, respectively. In human erythrocytes during embryonic development, the fetal (i) antigen is replaced by the adult (I) antigen as a result of the appearance of a beta-1,6-N acetylglucosaminyltransferase, the I-branching enzyme. Here, we report the cDNA cloning and expression of this branching enzyme that converts linear into branched poly-N-acetyllactosaminoglycans, thus introducing the I antigen in transfected cells. The cDNA sequence predicts a protein with type II membrane topology as has been found for all other mammalian glycosyltransferases cloned to date. The Chinese hamster ovary cells that stably express the isolated cDNA acquire I-branched structures as evidenced by the structural analysis of glycopeptides from these cells. Comparison of the amino acid sequence with those of other glycosyltransferases revealed that this I-branching enzyme and another beta-1,6-N-acetylglucosaminyltransferase that forms a branch in O-glycans are strongly homologous in the center of their putative catalytic domains. Moreover, the genes encoding these two beta-1,6-N-acetylglucosaminyltransferases were found to be located at the same locus on chromosome 9, band q21. These results indicate that the I-branching enzyme represents a member of a beta-1,6-N acetylglucosaminyltransferase gene family of which expression is controlled by developmental programs. PMID- 8449406 TI - SWI5 instability may be necessary but is not sufficient for asymmetric HO expression in yeast. AB - Homothallic haploid yeast cells divide to produce a mother cell that switches mating type and a daughter cell that does not. This pattern is the result of HO endonuclease transcription exclusively in mother cells, and there only transiently in late G1 as cells undergo Start. SWI5 encodes an HO transcription factor that is expressed during the S, G2, and M phases of the cell cycle. The lack of synthesis of SWI5 during G1 is essential to prevent HO transcription in daughter cells. Thus, HO must be activated by SWI5 protein synthesized in the previous cell cycle if it is to be properly regulated. SWI5 is inherited by both mother and daughter cells, and we show here that most of it is rapidly degraded during early G1. More stable mutant SWI5 proteins cause daughter cells to switch mating type, suggesting that SWI5 destruction is necessary to prevent HO expression in daughters. We show further that mother cells can still express HO when stimulated to undergo Start after arrest in early G1 for several hours. We propose that a small fraction of the SWI5 protein inherited by mother cells is extremely stable and that the crucial difference between mothers and daughters with regard to HO transcription is their differential ability to sequester SWI5 in a stable form, possibly as a component of transcription complexes on the HO promoter. PMID- 8449407 TI - The Trypanosoma cruzi ribosomal RNA-encoding gene: analysis of promoter and upstream intergenic spacer sequences. AB - The transcription start point (tsp) of the ribosomal RNA(rRNA)-encoding gene of Trypanosoma cruzi was mapped at 1550 bp upstream from the 18S rRNA coding sequence. The + 1 nucleotide (tsp) was determined to be a guanosine. As described for other eukaryotes, no consensus sequence was found when the putative promoter sequence (-200 to + 50) was compared with that described for Trypanosoma brucei and Crithidia fasciculata. However, a repeated element was found in the upstream intergenic spacer sequence (IGS) of T. cruzi. Motifs, present in this element, exhibit significant homology to the T. cruzi promoter sequence. Furthermore, the same motifs could be found, in a similar sequence organization, within the T. brucei promoter region. Therefore, the data described in this paper strongly indicate that the IGS rDNA (DNA coding for rRNA) organization in trypanosomatids appears similar to that found in higher eukaryotes. PMID- 8449408 TI - Characterization of the replication region of the small cryptic plasmid of Campylobacter hyointestinalis. AB - The complete nucleotide sequence of a 2.5-kb cryptic plasmid from Campylobacter hyointestinalis was determined. Only one open reading frame (ORF), encoding a polypeptide of M(r) 39,667, designated RepA, could be identified within the sequence. This was confirmed by minicell analysis. Analysis of the region upstream from the ORF showed an A+T-rich region followed by four 19-bp direct repeats. Together, these features are characteristic of other replication origins (ori(s)). The promoter sequence of the repA gene was identified by primer extension analysis and both the putative -10 and -35 regions were found to lie within two potential hairpin-loop structures. RepA showed marked amino acid sequence homology to a replication-initiation protein from the Neisseria gonorrhoeae plasmid, pFA3, and with other replication-initiation proteins over two conserved motifs. A putative partitioning (par) locus was identified upstream from the ori and consisted of a perfect 9-bp inverted repeat and six putative DNA gyrase-binding sites. A putative mobilization origin (oriT) region was identified. This featured a 19-bp imperfect inverted repeat adjacent to a sequence of 12 bp which showed strong homology to the consensus sequence of the 'nick regions' in a variety of oriTs of other plasmids. PMID- 8449409 TI - Isolation of a restriction-less mutant and development of a shuttle vector for the genetic analysis of Campylobacter hyointestinalis. AB - A cosmid shuttle cloning vector, pCHI15, was constructed which could be mobilized from Escherichia coli K-12 to a putative restriction-less mutant of Campylobacter hyointestinalis, C. fetus subsp. fetus, and C. fetus subsp. venerealis at a frequency of 10(-4) transconjugants per donor. A previously described C. coli shuttle vector, pILL550, could not be mobilized into the C. hyointestinalis restriction-less mutant, implying that the C. coli replicon was not functional in a C. hyointestinalis host. The type strains of C. jejuni, C. coli, C. fetus subsp. fetus, and C. hyointestinalis were analysed for their ability to be transformed by plasmid DNA which had been modified by other Campylobacter species. Each Campylobacter species was found to be most efficiently transformed by plasmid DNA that had been previously passaged in the same species. pCHI15 could be mobilized from C. coli into C. fetus subsp. fetus and the putative restriction-less mutant of C. hyointestinalis at a frequency of 3.0 x 10(-4) and 2.5 x 10(-3) transconjugants per donor, respectively. PMID- 8449410 TI - Evolutionary divergence of pobA, the structural gene encoding p-hydroxybenzoate hydroxylase in an Acinetobacter calcoaceticus strain well-suited for genetic analysis. AB - The pobA gene encoding p-hydroxybenzoate hydroxylase (PobA) from Acinetobacter calcoaceticus has been developed as a genetic tool for the analysis of structure function relationships in this enzyme. By exploiting the favorable genetic system of A. calcoaceticus strain ADP1, it is possible both to select and to map mutations which disturb PobA activity; characterization and sequence determination of mutants derived in this manner may complement site-directed studies with the homologous Pseudomonas aeruginosa gene. We have determined the nucleotide (nt) sequence of A. calcoaceticus pobA and performed a systematic comparison of the deduced amino acid (aa) sequence with that of the PobA enzyme from Pseudomonas fluorescens, for which the three-dimensional structure is known. Despite a 26% difference in the G+C content of the homologous genes, constraints against structural divergence of the proteins were revealed by an overall identity of 62.4% in the aligned aa sequences of PobA. Clusters of identical sequence occur at previously identified sites of ligand binding and at regions associated with subunit-subunit interaction. Based on the conservation of specific residues involved in flavin binding, we have assembled a consensus sequence for nicotinamide-flavoprotein monooxygenases which differs from that of the oxidoreductase class of flavoproteins. In addition to the conserved regions shared by the two PobA homologs, there are isolated pockets of divergence. The nt sequence divergence in one such region within the A. calcoaceticus gene can be attributed to the acquisition of short nt sequence repetitions. PMID- 8449411 TI - Cloning and expression of the polychlorinated biphenyl-degradation gene cluster from Arthrobacter M5 and comparison to analogous genes from gram-negative bacteria. AB - Arthrobacter M5 was characterized genetically to determine if the catabolic pathway (controlled by the bph genes), responsible for polychlorinated biphenyl (PCB) biodegradation in this Gram-positive strain, was similar to the pathways characterized from various Gram-negative bacteria. Arthrobacter M5 was originally isolated as a contaminant from a culture of the PCB degrader, Acinetobacter sp. strain P6. A bph-specific oligodeoxyribonucleotide (oligo) gene probe (bphC2) was designed by aligning the published sequences of two bphC genes (encoding 2,3 dihydroxybiphenyl dioxygenase) and synthesizing a 29-nucleotide (nt) fragment from a conserved region of the gene. The bphC2 oligo was used as a probe to identify a 10-kb HindIII fragment of total DNA from Arthrobacter M5 and subsequently to isolate Escherichia coli clones possessing bphC. The PCB degradation genes were expressed in E. coli, but expression was increased by subcloning in Pseudomonas aeruginosa. The nt and amino acid sequences of the region corresponding to the Arthrobacter M5 bphC gene showed a very high degree of homology with the published sequences of bphC genes from Gram-negative bacteria. PMID- 8449412 TI - Enhanced in vivo monooxygenase activities of mammalian P450s in engineered yeast cells producing high levels of NADPH-P450 reductase and human cytochrome b5. AB - We have engineered yeast genomic DNA to construct a set of strains producing various relative amounts of yeast NADPH-P450 reductase (Yred) and human cytochrome b5 (Hb5). Expression of cDNAs encoding human P450 1A1, 1A2, 3A4, 19A and mouse P450 1A1 in the different oxido-reduction backgrounds thus constituted were achieved after strain transformation by plasmid-based P450-encoding expression cassettes. The results indicate that the level of Yred strongly affects all activities tested. In contrast, the amount of Hb5 affects activities in a manner that is dependent both on the P450 isoform considered and the Yred level. In a strain containing optimized amounts of Hb5 and Yred, human P450 3A4 specific testosterone-6 beta-hydroxylase activity can be enhanced as much as 73 fold in comparison with the activity observed in a wild-type strain. Bioconversion of sterols or xenobiotics was easily achieved in vivo using this new co-expression system. PMID- 8449413 TI - Cloning and characterisation of pepC, a gene encoding a serine protease from Aspergillus niger. AB - We have cloned a gene, pepC, encoding a serine proteinase, PEPC, from Aspergillus niger by screening a phage lambda genomic DNA library with a gene (PRB1) from Saccharomyces cerevisiae which codes for proteinase YscB. The nucleotide (nt) sequence of pepC revealed that the gene is composed of two exons of 369 nt and 1230 nt separated by a single 70-nt intron. The deduced protein of 533 amino acids (aa) has a putative signal sequence for transport into the endoplasmic reticulum. Based on the extensive homology shown with serine proteinases (SerP) of the subtilisin family, which includes the active site triad, we hypothesise that the protein is made as a larger precursor which is matured by the cleavage of 130-140 aa from its N terminus and possibly by the removal of approx. 70 aa from its C terminus. PMID- 8449414 TI - Sequence motifs common to the EcoRII restriction endonuclease and the proposed sequence specificity domain of three DNA-[cytosine-C5] methyltransferases. AB - We have compared the deduced amino acid (aa) sequences of the EcoRII restriction endonuclease (R.EcoRII) and the proposed specificity (target recognition) domains of three DNA-[cytosine-C5] methyltransferases (MTases), M.EcoRII, M.Dcm, and M.SPR, each of which recognizes the same nucleotide sequence, CCWGG (where W is A or T). We have identified a region containing sequence motifs that are partially conserved in the MTases and R.EcoRII. This may be the first example of aa sequence homology between a MTase specificity (target recognition) domain and its cognate restriction endonuclease (ENase). It suggests that this region is important for DNA recognition by R.EcoRII and that the EcoRII ENase and MTase genes may have evolved from a common progenitor. PMID- 8449415 TI - Cloning, sequencing, and expression of a minor protease-encoding gene from Serratia marcescens ATCC21074. AB - The gene (smp) encoding an extracellular protease (Smp) from Serratia marcescens ATCC21074 has been cloned and expressed in Escherichia coli HB101. The nucleotide (nt) sequence of the cloned smp gene revealed a single open reading frame of 1056 bp coding for 352 amino acids (aa) (38,479 Da). The N-terminal aa sequence of Smp excreted from the E. coli host cells revealed that mature Smp consists of 300 aa (32,515 Da). The deduced aa sequence of Smp showed high overall homology (43%) to the Erwinia carotovora metalloprotease, but low homology (15-20%) to other metalloproteases, including the S. marcescens major metalloprotease. The location for three zinc ligands and the active site for Smp was predicted from other metalloproteases. The biochemical properties of Smp show that this enzyme is a metalloprotease whose activity is optimal at pH 8.0 and 50 degrees C. PMID- 8449416 TI - A gene encoding a small, acid-soluble spore protein from alkaliphilic Bacillus firmus OF4. AB - An 1100-bp DNA fragment cloned from alkaliphilic Bacillus firmus OF4 contained an open reading frame deduced to encode a 54-amino-acid, glutamine-rich protein with 35.6% identity to Bacillus subtilis small, acid-soluble spore protein-gamma (SASP gamma) in a 45-aa overlap. This ORF, designated sspA, lacks the lengthy sequence repeat characteristic of previously cloned SASP-gamma-encoding genes. Southern analysis under conditions of moderate stringency revealed six bands, suggesting the presence of several related genes in the alkaliphile. PMID- 8449417 TI - Secretion of a prokaryotic cellulase in bacterial and mammalian cells. AB - The catalytic domain of mature Clostridium thermocellum endoglucanase E (EGE') and derivatives of the enzyme fused to prokaryote and eukaryote signal peptides (SP), were produced in Chinese hamster ovary (CHO) cells and Escherichia coli. All three forms of the endoglucanase were secreted into the periplasm of Escherichia coli, but only derivatives of the enzyme containing an N-terminal SP were exported from CHO cells. Extracellular EGE', purified from E. coli and CHO cultures, displayed similar properties suggesting that glycosylation of the enzyme in the eukaryote did not significantly alter the protein's properties. Data presented in this report indicate that mature EGE' contains secretion signals which are recognised only by the E. coli protein export apparatus, suggesting that there are differences in the recognition of certain secretion signals in eukaryotes and prokaryotes. As mature EGE' does not contain secretion signals recognised by the mammalian cell, membrane translocation of the bacterial cellulase in a higher eukaryote is directed by an N-terminal prokaryotic SP. PMID- 8449419 TI - Ischemic stroke, Part 1: Early, accurate diagnosis. AB - To be consistent with a diagnosis of TIA or stroke, a focal neurologic deficit must have occurred suddenly. The differential diagnosis of TIA includes migraine aura (possibly without a headache), a hypotensive episode, radiculopathy, and an unusual seizure. Vascular risk factors (eg, hypertension, diabetes, smoking) and the extent of their control should be determined. Cardiac examination and ECG may provide important clues, as atrial fibrillation and valvular heart disorders are well recognized potential sources of emboli. During an acute stroke, CT is the best test to reliably distinguish between ischemic and hemorrhagic stroke. Other tests that may be indicated on an individual basis include MRI,, echocardiography, carotid duplex ultrasound, and arteriography. PMID- 8449418 TI - Cloning, sequence and expression of the argG gene from Streptomyces lavendulae. AB - The argG gene, encoding argininosuccinate synthetase, was cloned from Streptomyces lavendulae KCCS0055 by colony hybridization using the argG-carrying 2.1-kb fragment of S. coelicolor DNA as a probe. The restriction map of the cloned DNA fragment was very similar to that of S. coelicolor. This DNA fragment could complement the argG mutation of both S. lividans 1326 I10 and Escherichia coli K-12 JE5694, suggesting that the fragment contained a promoter for both E. coli and S. lividans. The subcloning experiment using E. coli K-12 JE5694 as a host has indicated that the essential region for argG is contained in the 2.5-kb DNA fragment. The translational product was identified as a 56-kDa kDa protein in minicells and by conventional gel electrophoresis. Determination of the nucleotide (nt) sequence of the 2.5-kb DNA fragment revealed one open reading frame of 1449 bp. The amino acid (aa) sequence analysis showed that the N terminus was Ser, and 9 aa from the N terminus were completely identical with those deduced from the nt sequence. Nuclease S1 mapping indicated that the transcription start point is located near the start codon. PMID- 8449420 TI - Ischemic stroke, Part 2: Optimal treatment and prevention. AB - The goal of medical treatment during acute cerebral infarction is to enhance thrombolysis and inhibit the chemical alterations associated with cell death. Treatment includes avoidance of blood pressure reduction, blood glucose control, possible anticoagulation with IV heparin, and sometimes reduction of cerebral edema. Optimal treatment thereafter depends on the result of patient evaluation. Uncontrolled vascular risk factor (eg, hypertension, smoking, and diabetes) should be treated. Aspirin and ticlopidine reduce the risk of recurrent ischemic stroke. In patients with nonrheumatic atrial fibrillation, anticoagulation with warfarin reduces the risk of embolic events. Carotid endarterectomy is superior to medical management alone in reducing the risk of stroke in patients with > 70% symptomatic extracranial carotid stenosis. PMID- 8449421 TI - Gastroesophageal reflux disease: diagnosis and medical therapy. AB - Gastroesophageal reflux disease (GERD) is a common clinical condition that affects all age groups, particularly older adults. Its presentation is diverse and can range from occasional heartburn to disabling complications. A complete history can usually lead to the diagnosis, although further testing may be needed for refractory symptoms, complications, and atypical presentations. Multiple therapeutic options are available, and decisions governing their use are based on symptoms and severity of esophagitis. All patients should be instructed to make dietary and other lifestyle adjustments. Antacids may be needed for mild symptoms. Pharmacologic options for moderately severe cases include H2 blockers, a proton pump inhibitor, or others. Surgery is reserved for cases of severe refractory disease. PMID- 8449422 TI - Delirium: diagnosis and treatment in the older patient. AB - Delirium is more common in older adults because of normal physiologic changes, increased incidence of medical illnesses, and increased medication use in this population. Older dementing patients are particularly predisposed to delirium because of associated neurologic abnormalities. Delirium often is superimposed on a dementing condition and may be difficult to differentiate from atypical dementia or a catastrophic reaction. Accurate diagnosis is essential, as is a thorough search for an underlying cause. The delirium will usually resolve if the underlying cause is properly treated. Treatment also requires maintaining a comfortable environment for the patient and, when necessary, administering a high potency neuroleptic. PMID- 8449423 TI - Playing doctor: practical advice from veteran physicians. PMID- 8449424 TI - The human life span: are we reaching the outer limits? PMID- 8449425 TI - AIDS: older patients aren't immune. PMID- 8449426 TI - The effect of maternal hypoxemia on the umbilical and femoral artery blood flow velocity waveforms and the relationship with mean arterial pressure in fetal sheep. AB - The relationship between the ratio femoral pulsatility index (PI)/umbilical PI and arterial oxygen content was examined in 8 fetal sheep at various stages of hypoxemia. This relationship was characterized by an inconsistent increase of the ratio femoral PI/umbilical PI at oxygen content levels beneath 1.0 mM. The correlation coefficient of the linear regression between both variables was only 0.54, indicating that prediction of fetal oxygenation on the basis of Doppler waveform measurements in peripheral fetal arteries might be invalid. The average correlation coefficient of the linear regressions between the femoral PI and fetal mean arterial pressure was 0.87 +/- 0.15 (SD), whereas the average correlation between the umbilical PI and fetal mean arterial pressure was 0.04 +/ 0.61. These data suggest that the degree of change in fetal mean arterial pressure considerably depends on the degree of change in vascular resistance in the fetal carcass. PMID- 8449427 TI - Changes in blood selenium and glutathione concentrations and glutathione peroxidase activity in human pregnancy. AB - Whole-blood and plasma selenium (Se) concentrations, red blood cell and plasma glutathione peroxidase activities, and red blood cell glutathione concentrations were investigated in 49 healthy pregnant women. Mean whole-blood and red blood cell Se concentrations started to decline after the 16th week and plasma Se after the 26th week of pregnancy. The lowest values were noted just before delivery. Negative correlations were found between the gestational age and both whole-blood and plasma Se concentrations: (r = -0.560 (p < 0.001) and r = -0.553 (p < 0.001), respectively. Plasma and red blood cell glutathione peroxidase activities started to decrease after the 20th and 30th week of pregnancy, respectively, and before delivery were significantly lower (p < 0.001) than during the 10th week of pregnancy. The red blood cell glutathione concentration increased significantly just before delivery. These results seem to confirm the supposition that in pregnant women with low or even moderate blood Se concentrations the requirement for the element significantly increases. PMID- 8449428 TI - Maternal-fetal substrate relationships in the third trimester in human pregnancy. AB - The maternal-fetal relationship of metabolic substrates was examined in 12 mothers undergoing cordocentesis for clinical reasons between 23 and 36 weeks' gestation. Twenty cordocentesis procedures were performed. Blood glucose, insulin, beta-hydroxybutyrate, glycerol and lactate were measured in simultaneously obtained maternal and fetal samples. There was a linear correlation between fetal and maternal concentration of glucose (y = 0.687x + 0.756, R2 = 0.65 and p = 0.001), and beta-hydroxybutyrate (y = 0.443x + 0.16, R2 = 0.938 and p = 0.0001). No relation between fetal insulin and glucose concentration was observed. No correlation was seen between maternal and fetal lactate concentration. The data on glycerol could be divided into two groups. When the fetal glycerol levels were below 100 mumol/l, the fetal glycerol concentration was always less than the simultaneously obtained maternal level. However, when the fetal glycerol levels were greater than 100 mumol/l, the corresponding maternal levels were lower than that in the fetus. The exact mechanism or significance of higher fetal glycerol levels remains unknown. These data demonstrate the usefulness of cordocentesis in the understanding of fetal metabolism. In correlation with isotopic tracer, cordocentesis could provide detailed insight into human fetus in the future. PMID- 8449429 TI - Effects of thromboxane synthetase inhibitor (OKY-046) on placental blood flow, placental weight and fetal weight in normotensive and spontaneously hypertensive rats. AB - Recently, thromboxane synthetase inhibitor has been used for the treatment of preeclampsia. In this study, we investigated the effects of thromboxane synthetase inhibitor (OKY-046) on placental blood flow (measured with clearance of hydrogen gas generated by electrolysis) in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The systolic blood pressure of OKY-046-treated SHR (1, 4 and 8 mg/kg) decreased significantly (p < 0.05); however, the systolic blood pressure of WKY did not decrease. The placental blood flow of both OKY-046-treated WKY and SHR did not decrease. We found that OKY-046 has no reducing effect on placental blood flow in rats, and systolic blood pressure of SHR decreases. These data suggest that thromboxane synthetase inhibitor might have a beneficial effect on preeclampsia. PMID- 8449430 TI - Prediction of high birthweight from maternal characteristics, symphysis fundal height and ultrasound biometry. AB - The possibility to predict a large infant during pregnancy was assessed using data from a prospective cohort study of 537 singleton pregnancies with term deliveries. Maternal characteristics, symphysis fundal height and ultrasound measurements were used in multivariate analyses for the prediction of an infant with a birthweight of > or = 4,500 or > or = 4,000 g. The positive predictive value was 55% for a birthweight > or = 4,000 g when only maternal characteristics were used, and increased slightly when symphysis fundal height was added. The corresponding value for a single ultrasound measurement at 37 gestational weeks was 52%. Using all available clinical data, positive predictive values of 45 and 80% could be achieved for birthweights of > or = 4,500 and > or = 4,000 g, respectively. PMID- 8449431 TI - Intracervical prostaglandin E2 gel for cervical ripening and labor induction: what is the appropriate dose? AB - In order to evaluate a dose-related response of cervical ripening and labor induction to a prostaglandin E2 (PGE2) gel, 110 women with uncomplicated postdate pregnancies and unripe cervices received intracervically 0.5 mg PGE2 (n = 40), 1.5 mg PGE2 (n = 35) or 2.5 mg PGE2 (n = 35). The failure rate in terms of cervical ripening was similar in all groups. Labor characteristics such as the duration of the latent phase as well as the total length of labor, the cesarean section rate, instrumental deliveries and neonatal outcome were similar in all groups. The number of women who required oxytocin for labor augmentation was negatively correlated to the dose of PGE2 (p < 0.05). In addition, 3 out of 35 women in the 2.5-mg group presented hypertonic uterine activity. The increase in the dose of PGE2 gel did not increase the possibility for a vaginal delivery, but reduced the requirement for oxytocin while increasing hypertonic uterine action. PMID- 8449432 TI - Is cesarean section necessary for delivery of a breech first twin? AB - Eighty-two pregnancies involving a breech first twin were retrospectively analyzed over two study periods during which the cesarean section rates were 20.9 and 94.9%, respectively. The neonatal and maternal morbidity in both study periods was compared. There were no neonatal deaths during either study period and no cases of interlocking twins among patients delivered vaginally. Neonatal morbidity was unrelated to the mode of delivery. The incidence of maternal fever was, however, significantly higher in the cesarean section group compared with the vaginal delivery group (p < 0.001). Our study suggests that vaginal delivery of selected twin gestations with a breech first twin should be an alternative to cesarean delivery. PMID- 8449433 TI - Estrous-cycle-related changes in the expression of mouse endometrial and oviductal glycoproteins. AB - Glycoproteins of mouse endometrium and oviduct were analyzed by lectin overlay blotting of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) separated whole-cell extracts, sampled at each of the four phases of the normal estrous cycle. Nine endometrial and 5 oviductal glycoproteins were found only in one of these two organs or showed cyclic changes in their expression as revealed by wheat germ or Ricinus communis I lectin blotting. Glycoproteins of the same molecular weight showed different expressions in the endometrium as compared with the oviduct. Thus one can conclude that the expression of the endometrial and oviductal glycoproteins is cyclic, but organ specific. PMID- 8449434 TI - Uterine contamination in the guinea pig following transcervical uterine monofilament insertion. AB - The effects of transcervical, intrauterine monofilaments on guinea pig uterine microflora were determined. The results indicated that bacteria were transferred to the uterus during the insertion process, although in sham control animals these bacteria were eradicated within 10 days. In the presence of an intrauterine substrate the bacteria within the uterus persisted for up to 6 months. Electron micrographs showed that bacteria were adhered to the monofilament within a biofilm, although some bacteria were planktonic. PMID- 8449435 TI - Activated protein C levels in patients with gynecologic tumors. AB - Activated protein C (APC) levels were measured in the plasma of patients with benign and malignant gynecologic tumors preoperatively, and on postoperative days 1 and 7. Preoperative levels of APC were found to be significantly low in both groups of patients compared to a group of healthy subjects. On postoperative day 1, levels of APC decreased significantly in both groups of patients compared to preoperative levels. By the 7th postoperative day, levels of APC in patients with benign tumors had increased significantly compared to postoperative day 1; levels in patients with malignant tumors, however, remained low. Our findings imply that there is a substantive correlation between gynecologic tumors, gynecologic surgery and the coagulation inhibitor, APC, which, in turn, can presumably be used to identify gynecologic patients who are at high risk for venous thrombosis. PMID- 8449436 TI - Successful outcome of pregnancy complicated with thyroidectomy-induced hypoparathyroidism and sudden dyspnea. A case report. AB - Total thyroidectomy is often accompanied with airway problem and hypoparathyroidism leading to infertility and pregnancy losses, and its effects are thus rarely reported on delivery. A patient with postoperative hypoparathyroidism carried a pregnancy to successful delivery, but suffered uncontrollable hypocalcemia and sudden respiratory distress at spontaneous labor onset. Both the fetal and maternal outcome were good. The acute deterioration in the hypoparathyroidism and airway problem at labor differed from the complications in previously reported cases. PMID- 8449437 TI - Pelvic-peritoneal tuberculosis with elevated serum and peritoneal fluid Ca-125 levels. A report of two cases. AB - We report 2 patients with pelvic-peritoneal tuberculosis and elevated serum and peritoneal fluid levels of Ca-125. The first was a young and infertile women who had cul-de-sac nodularity and dysmenorrhea. The other was postmenopausal and presented with weight loss and ascites. While a preoperative diagnosis of endometriosis was made in the former, intraperitoneal malignancy was considered in the latter. The diagnosis of pelvic-peritoneal tuberculosis was reached by laparoscopic-directed biopsy in both patients. Serum levels of Ca-125 returned to normal limits following antituberculous drug treatment. PMID- 8449438 TI - A follicular cyst during tamoxifen therapy in a premenopausal breast cancer woman. AB - A large ovarian follicular cyst developed on day 43 of low-dose tamoxifen adjuvant therapy for a premenopausal breast cancer (total drug intake: 860 mg). The serum estradiol level increased to almost ten times the pretreatment level. However, the FSH and LH decreased slightly, and the serum progesterone level remained almost unchanged. It is hypothesized that tamoxifen acted directly on the ovaries to provoke excessive proliferation of the granulosa cells in a follicular cyst, causing it to grow very large, and resulting in elevated E2 levels. PMID- 8449439 TI - Catecholamine concentrations in venous plasma and cerebrospinal fluid in normal and complicated pregnancy. AB - The concentrations of adrenaline and noradrenaline were determined in venous plasma and cerebrospinal fluid (CSF) of 41 pregnant women at term scheduled for elective or 'hot' caesarean section and in 7 healthy non-pregnant women scheduled for elective surgery. Group 1: 10 pregnant women at term with a normal history of their pregnancy; group 2: like group 1, but in active labour for more than 4 h; group 3: 10 pregnant women with insulin-dependent diabetes mellitus with or without slightly elevated arterial blood pressure; group 4: 11 women with pre eclampsia gravis; group 5: 7 healthy non-pregnant women of fertile age. The highest values of mean arterial blood pressure and of venous plasma noradrenaline were found in the pre-eclamptic group 4, mean arterial blood pressure and plasma noradrenaline levels correlated to each other. However, concentrations of noradrenaline in CSF in group 4 did not differ significantly from the other groups. It is speculated that a different origin of hypertension may be the reason for the normal noradrenaline concentrations in CSF. This finding is in contrast to earlier findings in which noradrenaline levels in CSF were elevated in patients with essential hypertension. PMID- 8449440 TI - Materno-fetal transmission of pregnancy malaria: an immunoparasitological study on 202 parturients in Maputo. AB - A total of 202 delivering mothers and their newborns were studied with the intention to follow the materno-fetal transmission of malaria. Malaria infection was encountered in 35 cases (17.3%) in which Plasmodium falciparum predominated in peripheral blood while P. malariae predominated on the placental surface. In cord blood P. falciparum was encountered in 1.5% of the cases. There was slightly more maternal infection in rural (23%) than in suburban areas (19%). Less malaria infection was encountered in primiparas than in multiparas and there was similar antibody response in both mothers and their newborns. Anaemia was encountered in 70% of the mothers and in 93% of the newborns. There was no significant correlation between low birthweight of the newborn and malaria parasitaemia in the mother. PMID- 8449441 TI - Intrauterine infections and their association with stillbirth and preterm birth in Maputo, Mozambique. AB - Subclinical intrauterine infections during pregnancy in Mozambican women were studied in an attempt to elucidate their potential association with adverse pregnancy outcome, particularly stillbirth and preterm birth. A total of 39 stillbirths and 21 preterm live births were compared with 121 term live births. Extraplacental membranes and amniotic fluid were studied to ascertain the presence or absence of chorioamnionitis and of antibacterial activity in amniotic fluid. It was found that signs of maternal subclinical disease in extraplacental membranes in combination with an absence of antibacterial activity in amniotic fluid was overrepresented in stillbirths and preterm births in relation to term live births. A tentative conclusion is that a lack of antibacterial activity in amniotic fluid and established chorioamnionitis represent a vicious combination with strongly negative significance for the fetal outcome. PMID- 8449442 TI - Vaginocavernosus reflex. Clinical significance and role in sexual act. AB - The action and clinical significance of the vaginocavernosus reflex was studied in 17 healthy women with a mean age of 36.6 years. The response of the bulbo- and ischiocavernosus muscles to rapid vaginal distension by balloon was recorded by a needle electrode inserted in each muscle and displayed on the screen of an EMG apparatus. The two cavernosus muscles contracted on vaginal distension; the amplitude of contraction increased with the increase of volume of vaginal inflation. The reflex contraction was not evoked after frequent successive or slow inflations or upon inflation of the anesthetized vagina. The latency of the reflex decreased with increased volume of vaginal inflation. The reflex cavernosus muscle contraction on vaginal distension during the sexual act seems to enhance both the clitoris and penile erection. This is believed to result from the compression exerted on both the deep dorsal vein of the penis and the erectile cavernous tissue. Also, cavernosus muscles contraction may help to milk the semen in the penile urethra into the vagina while the penis is being withdrawn from the vagina after ejaculation. Furthermore, vaginal distension by the fetal head during delivery induces cavernosus muscles contraction, which is suggested to support the head during its descent and prevent vaginal and perineal tears. PMID- 8449444 TI - Hematosalpinx and torsion of the fallopian tube in a virgin girl. AB - Torsion of the fallopian tube is encountered in the diseased tube. The present report describes a hematosalpinx and its tubal torsion in a virgin girl who experienced no prior predisposing factors suggested for tubal obstruction and adhesions. This rare case may highlight a new insight into pathophysiology of tubal torsion associated with hematosalpinx. PMID- 8449443 TI - Ultrasound-guided aspiration for relief of pain generated by simple ovarian cysts. AB - Over a 2-year period, ultrasound-guided aspiration of painful, presumptively benign ovarian cysts was performed in 18 women < 40 years old. Aspiration was performed either transvaginally (12 patients) or transabdominally (6 patients) depending on the cyst location. Neither anaesthesia nor analgesia were used, and all patients had immediate pain relief, and escaped immediate surgical intervention. None had complications or evidence of malignant cells on cytologic examination, and all were discharged within 24 h of the procedure. The recurrence rate within 1 year of the procedure was 11.1%. The procedure appeared to be a good and safe alternative to surgery. PMID- 8449445 TI - Morular metaplasia of the endometrium in a patient with polycystic ovary syndrome. AB - A 31-year-old women with polycystic ovary syndrome underwent dilatation and curettage (D&C) as part of her infertility workup. Pathologic examination revealed endometrial morular metaplasia without malignant potential. Follow-up D&C had no evidence of endometrial hyperplasia or carcinoma. The diagnostic difficulties and pathogenesis are discussed. PMID- 8449446 TI - No beneficial effects of human growth hormone therapy in normal ovulatory patients with a poor ovarian response to gonadotropins. AB - We studied the effects of human growth hormone (hGH) in 7 in vitro fertilization (IVF) patients with normal ovulatory menstrual cycles who showed a low response to ovarian stimulation with follicle-stimulating hormone (FSH) and human menopausal gonadotropin (hMG). Human growth hormone therapy had no significant effect on the number of days of gonadotropic stimulation, on the total amount of hMG administered, on the serum estradiol level on the day of human chorionic gonadotropin injection, or on the IVF outcome. Our preliminary results do not encourage the routine use of hGH to improve IVF outcome in normogonadotropic ovulatory patients who respond poorly to the standard FSH/hMG protocol. PMID- 8449447 TI - Two-dimensional electrophoretic analysis of endometrial cellular proteins synthesized during early pregnancy in the mouse. AB - The synthesis of cellular proteins during early pregnancy was analyzed in mouse endometria incubated in vitro in the presence of [35S]-methionine. Endometrial proteins labelled on days 3 and 5 of pregnancy were compared with proteins from nonpregnant proestrus-phase endometrium. We have identified 23 proteins that were differentially expressed. These proteins were divided into four groups: (1) 10 proteins synthesized most prominently in nonpregnant proestrus-phase endometrium that decrease or disappear in pregnancy; (2) 4 proteins that are synthesized only on day 3, i.e., in the immediate preimplantation period; (3) 3 proteins that appear only on day 5 coincidentally with the development of decidua; (4) 5 proteins that are synthesized by both day 3 and day 5 endometria but are not found in the nonpregnant endometrium. Hence, the synthesis of some endometrial cellular proteins increased and others decreased in early pregnancy. The function of these proteins is unknown. Four proteins (Mr 26, 51, 52 and 70 kDa), 2 of which are both cell associated and secreted (Mr 52 and 70 kd) were selectively synthesized in the preimplantation period and thus may mediate implantation. PMID- 8449448 TI - Fetal metatarsal length: an accurate predictor of gestational age and weight in the ovine fetus. AB - Accurate assessment of gestational age and fetal weight in the pregnant ewe is important in both acute and longitudinal perinatal studies. We describe two morphometric methods based on the length of the fetal metatarsal bone. These measurements can be made intraoperatively or at postmortem. Metatarsal bone lengths can be used to better predict gestational age and fetal weight than previously described methods. PMID- 8449449 TI - Women with prolactin-producing pituitary adenoma show decreased serum placental lactogen during pregnancy. AB - Prolactin (PRL), growth hormone (GH), placental lactogen (PL), chorionic gonadotropin (CG), estradiol (OE), progesterone (P4) and sex hormone-binding globulin (SHBG) were measured in serum throughout gestation in 9 women with PRL producing pituitary adenomas. They had been treated at least 1 year with the dopamine agonist bromocriptine before pregnancy occurred. All women bore healthy babies of normal birthweight. Their PRL levels did not show the successive increase seen in normal pregnancies; serum PRL was unphysiologically increased in all patients up to the 20th week of gestation, whereafter PRL levelled off and fell within the normal range. Serum PL levels were lower in the women with prolactinoma compared to healthy pregnant women, despite normal placental weight. The serum GH levels in the patients determined with an immunoassay based on a monoclonal antibody, were low or nondetectable, similar to healthy pregnant controls. In contrast, high molecular weight GH in serum as determined with a monoclonal antibody which also recognizes PL appeared to be increased in comparison with healthy pregnant women. The serum levels of CG, OE, P4 and SHBG were all within the normal range. These results show that the unphysiological secretion of PRL in pregnant women with PRL-producing pituitary adenomas is associated with decreased serum levels of PL. PMID- 8449450 TI - Serotonin-induced vasoconstriction in human placental chorionic veins: interaction with prostaglandin F2 alpha. AB - In vitro experiments using isolated rings and perfused segments of human chorionic veins, were designed to determine the effects of serotonin and their interaction with PGF2 alpha on vascular tension and perfusion pressure. These vessels responded vigorously with high sensitivity to the vasoconstrictor effects of serotonin in both experimental designs. Administration of PGF2 alpha also led to constriction of the veins, but this autacoid is at least 100 times less potent than serotonin. When adding PGF2 alpha previously to serotonin to the bathing fluid or to the perfusate, the serotonin response was significantly potentiated, increasing the maximal contractile response in 116 +/- 12% and the perfusion pressure in 180 +/- 25%. Both autacoids probably operate in this vascular bed interacting with each other and playing an important role in the regulation of placental blood flow in vivo. PMID- 8449451 TI - Hydramnios in singleton pregnancy: sonographic prevalence and etiology. AB - One hundred and forty-nine cases of hydramnios were detected among 13,750 parturients undergoing 25,000 routine ultrasonographic examinations. The prevalence of hydramnios was 1.08%. Ninety-seven patients (65.1%) had no apparent cause for the increased amount of fluid volume. Twenty-eight newborns (18.8%) were congenitally malformed, and 22 (14.8%) patients had diabetes mellitus. Rh incompatibility accounted for only 1.3% of the cases. It seems that with the improvement of modern obstetrics, mainly improving the antenatal management of diabetes and Rh incompatibility, there is a decrease in the relative incidence of these two conditions as etiological factors of hydramnios. PMID- 8449452 TI - Ultrasonic evaluation of hydronephrosis during pregnancy and puerperium. AB - Hydronephrosis frequently occurs during pregnancy. The etiology and significance of this phenomenon are not clearly understood. Further, little information regarding changes in the kidneys during pregnancy and early postpartum is available. This study uses real-time ultrasound in order to investigate whether or not there is a relationship between the degree of calyceal dilatation, kidney size, and creatinine clearance value. Two hundred and eighty-six patients, including 175 pregnant and 111 puerperal individuals, were examined. The overall incidence of hydronephrosis was 67% in the pregnant and 39% in the puerperal women. Moderately and severely affected kidneys were significantly larger than the mildly affected and nonaffected kidneys (p < 0.05, p < 0.001). The creatinine clearance value was lower in patients with severe hydronephrosis than in those with mild and moderate hydronephrosis and in the nonaffected patients, albeit with no statistical significance. PMID- 8449453 TI - Influence of labour on epidermal growth factor receptor distribution of the human chorion at term gestation. AB - Chorion was obtained from 10 healthy pregnant women at term gestation who were delivered either vaginally (n = 5) or by elective repeat caesarean section before the onset of labour (n = 5). Epidermal growth factor (EGF) receptors in chorionic tissue were evaluated by means of freeze fracture technique (label fracture). They were found to be significantly less, but more frequently coupled, in specimens obtained after labour than before the onset of labour. These findings suggest that a functional activation of EGF receptors in human chorion might occur during labour. PMID- 8449454 TI - Number of animals for sequential testing. AB - US regulatory agencies have used six animals in eye irritation tests. Analyses of eye irritation tests on pesticides (n = 48), consumer products and cosmetics (n = 53), Marzulli and Ruggles database (n = 139), and cleaning products and ingredients (n = 30) have greatly extended previous investigations of the merit of reducing animal sample size in the eye test. Given the existing scoring system for positive animal responses (corneal opacity > or = 1, iritis > or = 1, conjunctival redness > or = 2 and conjunctival chemosis > or = 2), the accuracy of the classification systems currently used by these agencies was determined. The US Consumer Product Safety Commission, US Food and Drug Administration, and US Occupational Safety and Health Administration use a classification system by which a substance is designated as an irritant when at least four of six animals give a positive response. This decision rule leads to a very high accuracy of at least 99% with essentially no false positive and false negative judgments. In contrast, the system used by the US Environmental Protection Agency pesticide program, in which only one or more of six treated animals result in an irritant decision, has an accuracy of only 50-80% with very high false positive rates. Analyses indicated that test sample size could be reduced to three and still preserve very good accuracy, whereas two-animal and one-animal tests did not give satisfactory responses. A two-stage test, in which two animals are tested and evaluated in the first stage before the need for testing one more animal in the second stage is determined, also demonstrated good operating characteristics. Both the one-stage/three-animal test and the two-stage test deserve consideration. PMID- 8449455 TI - Scoring for eye irritation tests. AB - Scoring of the rabbit eye test and the resulting evaluation and classification should provide useful information about the likelihood that a test material may cause injury on contact with the human eye. When an animal test is necessary, a rabbit eye test based on the following characteristics is proposed for deriving the maximum information from the fewest animals. The ocular effects of interest should include corneal opacity, iritis and conjunctival redness. Animals should be scored for each ocular effect at 24, 48 and 72 hr after the test substance is administered. If an animal is negative at all three scoring times, it can be removed from the test at 72 hr. If it shows a positive effect at a scoring time but the lesion clears at 72 hr, it can be removed at 72 hr. If it shows a positive effect that does not clear at 72 hr, it should be scored again on day 7 when the test ends. However, if an animal shows severe effects at one or more scoring times, it can be removed from the test at 72 hr. An animal is positive if any one of the following criteria is observed at 24, 48 or 72 hr: corneal opacity of 1 or above, iritis of 1 or above, or conjunctival redness of 2 or above. Severe ocular effects (noted at 24, 48 or 72 hr) that may endanger sight deserve special recognition for the classification of chemicals and include corneal opacity of 3 or above, or iritis of 2. This proposal is consistent with the opinions of the majority of respondents who attended the Workshop on Updating Eye Irritation Test Methods, Proposals for Regulatory Consensus. The most notable exception was the suggestion by respondents to add conjunctival chemosis as one of the scoring parameters. PMID- 8449456 TI - An eye irritation test protocol and an evaluation and classification system. AB - An in vivo test protocol and an evaluation and classification system for the determination of eye irritation potential of chemicals and mixtures (substances) is proposed. The protocol uses two or three rabbits and reduces distress in test animals. The test substances are classified as non-irritant, irritant or severe irritant to meet regulatory needs. They may be classified on the basis of past experience with similar compounds or mixtures. Screens such as structure-activity relationships, pH extremes, validated and accepted in vitro tests, severe dermal irritation (primary dermal irritation index > or = 5) or severe dermal toxicity (lethality at < 200 mg/kg body weight) should be used to classify irritant or severe irritant materials when one or more of the screens can provide convincing evidence. For suspected severe irritant materials, the proposed in vivo test permits the use of one rabbit and instillation of 0.01 ml (0.01 g) of the test material into the cornea. Materials that are not classified irritant or severe irritant by screens or severe irritant by one rabbit test are tested in two or three rabbits; 0.1 ml (0.1 g) is instilled into the conjunctival sac. The responses (corneal opacity, iritis and conjunctival redness) are scored according to the modified Draize scoring system at 24, 48 and 72 hr and 7 days post instillation. A rabbit is considered positive when corneal opacity of 1 or above, iritis of 1 or above or conjunctival redness of 2 or above is present at 24, 48 or 72 hr post-instillation. The material is classified as a severe irritant when the rabbit in the one-animal test or two or more rabbits in the standard test have responses of corneal opacity of 3 or above and iritis of 2 at 24, 48 or 72 hr, or positive responses on day 7 after instillation. The material is classified as an eye irritant when two or more rabbits are positive but the responses are not severe and they clear 7 days after instillation. The material is classified as a non-irritant when no more than one rabbit is positive. The opinions expressed in this article are those of the authors and do not necessarily reflect the views of US Federal agencies. PMID- 8449457 TI - Subacute (4-wk) oral toxicity of a combination of four nephrotoxins in rats: comparison with the toxicity of the individual compounds. AB - In a 4-wk study, 10-wk-old Wistar rats were fed the nephrotoxins hexachloro-1,3 butadiene (HCBD), mercuric chloride, d-limonene and lysinoalanine either alone or in combination. These nephrotoxins damage epithelial cells of the proximal tubules, but by different mechanisms. Each chemical was given alone at a Minimum Nephrotoxic-Effect Level (MNEL), and at a No-Nephrotoxic-Effect Level (NNEL). The combination was given at the MNEL, the NNEL and one-quarter of the NNEL of the individual chemicals. The individual nephrotoxins caused slight growth depression in males at the MNEL, but not at the NNEL, whereas the combination depressed growth slightly at the NNEL and severely at the MNEL. In females at the MNEL, only HCBD retarded growth; in contrast to the effect in males this was not aggravated by combined treatment. Nephrotoxicity was more severe in males fed the combination than in males given the nephrotoxins alone. The former showed decreased renal concentrating ability and moderate histopathological changes in the kidneys at the MNEL, and a dose-dependent increase in kidney weight and number of epithelial cells in the urine at the NNEL and the MNEL. The males treated with a single agent showed slightly increased kidney weights, and/or slight histopathological changes in the kidneys at the MNEL, and (with d-limonene only) epithelial cells in the urine at the NNEL and MNEL. In females, renal changes induced by the combination were not more severe than those observed with individual compounds. No adverse changes attributable to treatment were observed in rats fed the combination at one-quarter of the NNEL. In the present study, combined exposure to four nephrotoxins at their individual NNEL did not constitute an obviously increased hazard, indicating absence of synergistic interaction, whereas at the MNEL clearly enhanced (renal) toxicity occurred in males, although not in females. PMID- 8449458 TI - Culture of precision-cut liver slices: effect of some peroxisome proliferators. AB - Precision-cut rat liver slices were prepared with a Krumdieck tissue slicer and cultured in three standard hepatocyte culture media. Rat liver slices cultured in either RPMI 1640 medium or Williams Medium E could be maintained in culture for up to 72 hr. In contrast, Leibovitz's L-15 medium was unsatisfactory in that slice viability, assessed either by morphological examination or by measurement of enzyme activities, could not be maintained for periods greater than 24 hr. As a measure of functional viability liver slices were cultured with some known rodent peroxisome proliferators, namely clofibric acid, nafenopin, ciprofibrate and Wy-14,643. The peroxisome proliferators induced both palmitoyl CoA oxidation and carnitine acetyltransferase activities in 48- and 72-hr slice cultures. Ultrastructural examination of liver slices cultured with either ciprofibrate or Wy-14,643 for 72 hr revealed an increase in the number of peroxisomes. These results demonstrate that rat liver slices may be maintained in culture for up to 72 hr, and that they respond in a similar manner to rat primary hepatocyte cultures to some peroxisome proliferators. Precision-cut liver slices may therefore be a useful alternative in vitro system to hepatocyte cultures for screening compounds for effects on enzyme activities and for assessing species differences in response. PMID- 8449459 TI - The Leon Golberg Memorial Lecture. Should Britain have a medicines and food control agency? PMID- 8449460 TI - Criteria for in vitro alternatives for the eye irritation test. AB - A proposal encompassing considerations and criteria for the development of in vitro alternatives to the eye irritation test has been developed and is presented here. Two factors need to be considered initially in developing an alternative test. The first is to determine whether the alternative assay is to be used as a screen or as a replacement for the eye irritation test. Less stringent acceptance criteria are required for an assay used as a screen than for that used as a replacement test. A screen is a preliminary test for the assessment of eye irritation. It is used for making preliminary decisions or establishing the direction for further testing. Screens answer fewer and less complex questions than a replacement test would, since the results from screens are usually confirmed by more definitive testing. A replacement test, however, must provide the same answers as in vivo methods for the assessment of eye irritation and must provide data for making a definitive toxicological assessment of eye irritation. The second factor to be considered is knowledge of the in vivo assay intended to be replaced. This knowledge should include the procedural aspects of the test and the regulatory information it provides. The following may be considered as criteria for in vitro tests used as screens or as replacements for the eye irritation test in rabbits: rationale (there should be a clear statement regarding the rationale for the use of a particular test in relation to the availability of other tests); relevance (the in vitro endpoint should have biological or physiological relevance to the effect to be detected in vivo); and validational (intralaboratory as well as interlaboratory validation must be conducted). PMID- 8449461 TI - Screening procedures for eye irritation. AB - Screens aid in identifying some severe irritants or corrosives and eliminating them from consideration for in vivo eye irritation testing. Products may be evaluated for ocular irritation potential in a stepwise progression as follows: (1) products at pH extremes of 2 or below or of 11.5 or above may be considered to be ocular irritants; (2) based on chemical structure-activity considerations, some products may be judged to have ocular irritation potential; (3) validated and accepted in vitro systems may possibly be used as a screen in the future; (4) when a test material demonstrates severe acute dermal toxicity (lethality at < or = 200 mg/kg body weight), further testing for either dermal or ocular irritation may not need to be undertaken; (5) if a substance shows a primary dermal irritation index of 5 or above, it may be considered to be an ocular irritant; (6) materials that are not removed from consideration based on these proposed screens may then be considered for testing for ocular irritation in rabbits under accepted procedures. In a survey given to participants in the workshop, a high percentage believed that screens should be used. However, opinions on the use of the individual screens varied between the different interested groups attending, with the possible future use of in vitro screens for specific product lines having the highest percentage of agreement (57-100%). PMID- 8449462 TI - Use of ophthalmic topical anaesthetics. AB - Pretreatment of the eyes of rabbits with a topical anaesthetic can be viewed as a refinement of the test for eye irritation. It reduces pain at the time of test material administration, decreases animal distress and permits easier application of the test agent to the eye. In some cases, however, use of an anaesthetic either alone or in combination with the test substance may alter ocular responses or provide little benefit. Although anaesthetic pretreatment may result in decreased pain at the time of test-compound administration, it does not affect possible pain after the effects of the anaesthetic have dissipated. Some anaesthetics are themselves irritating to eyes. In addition, anaesthetics reduce blinking and tearing, thereby maintaining the test-material concentration at the surface of the eye longer. Corneal permeability may also be increased with pretreatment use of an anaesthetic, and may bring the test agent into contact with more structures of the eye. Some anaesthetics delay healing after ocular injury. All of these varied effects may result in increased irritation to the eye. Overall, pretreatment with anaesthetics has usually resulted in a tendency for slightly higher irritation scores; eye irritancy classification is usually unaffected. PMID- 8449463 TI - The use of low-volume dosing in the eye irritation test. AB - The Draize rabbit eye test was developed to provide a method for assessing the irritation potential of materials that might come in contact with human eyes. The method involves the instillation of 0.1 ml of a test liquid (100 mg solid) into the conjunctival sac of an animal's eye. A refinement of the Draize test is the low-volume eye test in which 0.01 ml of a substance is placed directly on the cornea of the eye. Studies indicate that the low-volume method provides a better correlation to human eye irritation experience for some substances. The Interagency Regulatory Alternatives Group (IRAG) proposes that the low-volume eye test can be used to substantiate the irritancy of suspect severe ocular irritants that have not been eliminated by various pre-eye test 'screens'. A substance testing positive by the low-volume method can be classified as an irritant; one that tests negative will require further testing by the use of the 0.1-ml volume procedure. For all other definitive testing, the Draize test (0.1 ml) should be used. Results from a questionnaire distributed at the IRAG workshop showed that many workshop participants thought that the low-volume test should be used as an eye irritation screening procedure. PMID- 8449464 TI - [Diagnosis and therapy of hemorrhoids. New knowledge in sclerotherapy]. AB - FUNDAMENTAL REMARKS: Successful treatment of hemorrhoids stands and falls with the correct diagnosis. MAIN TOPICS: Where conservative treatment measures are justified and surgical intervention can be foregone, new studies on the sclerotherapy of hemorrhoids have led to a change in therapeutic objectives. Accordingly, in the case of enlarged symptomatic hemorrhoids an attempt should not be made primarily to reduce their size; rather, the usually caudally displaced hemorrhoidal convolutes should be fixed again above the dentate line. This is achieved by injecting the sclerosant not as previously into the center of the hemorrhoid convolute, but into the base between hemorrhoids and the adjacent muscular layer. This does not lead to destruction of the hemorrhoids with possible impairment of their function, but to the desired fixation. In this way, irrespective of the degree of the hemorrhoidal disease the danger that, on defecation, the hemorrhoids are forced into the anal channel, is avoided. If the hemorrhoids cannot be fixed in the way described, only surgical measures will lead to success. CONCLUSIONS: Sclerotherapy of hemorrhoids should not be aimed at shrinking, but fixing them. Should the objective not be achieved after two or three treatment sessions, surgery should be considered. PMID- 8449465 TI - [Progress in pneumology. Can the most prevalent diseases be controlled?]. PMID- 8449467 TI - [Diagnosis in family practice. Part 4: Fatigue]. PMID- 8449466 TI - [Radiotherapy in scar-induced keloid]. AB - AIMS: In a retrospective study, the results of the excision of keloids in combination with postoperative irradiation were investigated with respect to the cosmetic effect and the recurrence rate. PATIENTS: Between 1978 and 1990, 20 patients aged between 15 and 64 years who, together, had a total of 23 localized keloids, were submitted to prophylactic irradiation following excision of the latter. TREATMENT: Radiotherapy was applied, fractionated, using low-energy (soft) X-rays, the strontium 90 Dermaplatte, or with electrons produced by a linear accelerator. The mean total surface dose applied was 20 Gy. RESULTS: Eighteen patients with 21 keloids were followed-up for a period of between 2 months and 12 years (mean: 33 months). The cosmetic result was good or very good in 17, and unsatisfactory in four of the 21 keloids. Prior to treatment, 18 of the keloids were associated with local complaints; 15 of these cases were symptom free after treatment. CONCLUSION: With the combination of excision and postoperative irradiation, the results of keloid treatment can be improved, and recurrence largely avoided. PMID- 8449468 TI - [Long-term treatment of mucoviscidosis. Results with a microencapsulated pancreatic enzyme preparation]. AB - METHODS: In 30 children suffering from cystic fibrosis, the long-term effect (2 years) of treatment with an acid-protected micro-encapsulated pancreatin preparation was investigated in comparison with prior enzyme replacement with a conventional pancreatin preparation given over a period of years. Assessment criteria was the development of body length and body weight, lung function (vital capacity, FEF1) and the Shwachman-Kulczycki score. RESULTS: The therapeutic efficacy of the acid-protected micro-encapsulated preparation is considered to be higher than that of conventional preparations, since the same effect was achieved with only one-quarter to one-third of the pancreatin dose of the conventional preparation (average: 6.5 +/- 2.9 g pancreatin/d, as compared with 1.6 +/- 0.6 g pancreatin in the case of the acid-protected micro-encapsulated preparation). However, none of the clinical parameters investigated revealed any significant changes during the course of the observation period. The results indicate that, if the general state of health and nutritional status of patients with cystic fibrosis is to be improved further, in addition to a special diet, attempts must be made to achieve further optimization of the intraluminal digestion. PMID- 8449469 TI - [No leeway for the physician's moral decision?]. PMID- 8449470 TI - [Blood sedimentation--hemorheology in general practice]. AB - AIMS: To describe the principle, measuring procedures and clinical information yield of the erythrocyte sedimentation rate with particular consideration of hemorrheological aspects. MAJOR POINTS CONSIDERED: ESR is a well established procedure with a checkered past which continues to be of considerable importance for screening purposes. Although the ESR is easy to carry out, the physical phenomena on which it is based are highly complicated. The measured value obtained is determined by a number of interacting factors. What is not well known is the fact that, in principle, it is a hemorrheological procedure. Numerous sources of error capable of affecting the ESR value must be taken into account. CONCLUSION: More recent developments suggest that ESR will continue to be of considerable value as a simple and inexpensive screening procedure. PMID- 8449472 TI - [Normal and abnormal gastrointestinal motility]. AB - BASIC REMARKS: For the diagnostic evaluation of gastrointestinal disorders of motility and function, there is a growing number of examination procedures available which, after excluding organic disease, are usually capable of differentiating the underlying problem. MAIN POINTS DISCUSSED: Arranged in accordance with the disorders of the various segments of the gastrointestinal tract, the major procedures together with their suitability for the establishment of the respective clinical problem presenting are discussed. On account of the considerable expenditure involved, however, the indication for a diagnostic evaluation of function needs to be established on a very stringent basis and, as a rule, is given only when tentative symptomatic treatment has failed. Exceptions are non-cardiac chest pain, achalasia and fecal incontinence, in which, owing to the usually severe nature of the illness, an etiological clarification and appropriate therapy are a must. PMID- 8449471 TI - [Lipid metabolism--effect of cardiac agents and ACE inhibitors. Effects of anti arrhythmia agents, ACE inhibitors, positive inotropic substance and anti-angina agents]. AB - AIM: Cardio-active substances and ACE-Inhibitors are often employed in patients with metabolic disturbances. The question as to whether they have any effect on the lipid levels therefore needs to be answered. MAJOR POINTS STUDIED: The effects of antiarrhythmics, ACE-inhibitors, positively inotropic substances and antianginal substances on lipid metabolism are discussed on the basis of a search through the literature. The wealth of data permit the conclusion that many of the drugs in these substance groups are neutral in terms of metabolism. There are, however, also individual substances that lead to an elevation of lipid levels. Via an improvement in glucose tolerance, ACE-inhibitors can contribute to a lowering of triglyceride concentrations and an increase in the HDL cholesterol levels. For a number of substance groups, the data available still do not suffice to permit a definitive conclusion to be drawn. CONCLUSION: In the case of treatment with the above-mentioned substance groups, effects on lipid metabolism should be checked wherever this is in doubt. This applies, of course, in particular to patients already suffering from hyperlipoproteinemia. PMID- 8449473 TI - [Diagnosis in general practice. Part 5: Cough]. PMID- 8449474 TI - [Allergic bronchial asthma treated with Loratadine]. AB - AIMS: To test the efficacy and tolerability of loratadin, a new anthihistaminic agent in allergic bronchial asthma administered as adjunctive treatment in persistent asthma. METHOD: Eight-week open clinical trial. The 25 ambulatory patients retained existing treatment for asthma during the duration of the study. A two-week period of observation without the drug under investigation was followed by a six-week therapeutic phase, during which a single daily dose of 10 mg loratadine was taken. H1 antihistaminics, DNCG, ketotifene and systemic corticoids were not permitted. To monitor the therapeutic effect, the lung function parameters (VC, FEV1, peak flow, resistance) and the symptom score were established. RESULTS: In comparison with the results of lung function testing during the pre-phase, the loratadine phase improved the parameters by up to 21%. The number of apneic events recorded in the patient's diary decreased by about 52%, the attacks of coughing diminished in the evaluation score from 8.5 to 3.0. For the rest, a significant decrease in the consumption of inhalative sympathomimetics was noted. In the overall assessment, 71% of the patients noted a good therapeutic response. CONCLUSIONS: The results of this study show that loratadine, employed as an adjuvant therapeutic agent for the treatment of allergic bronchial asthma has a positive effect on symptomatology. PMID- 8449475 TI - [Tourette syndrome in progressive dementia]. PMID- 8449476 TI - [The significance of psychodynamic relationship factors for psychopathogenesis in childhood Nazi persecution]. AB - This study focuses on psychiatric disorders following extreme traumatisation experienced by children born during the Holocaust in World War II. According to numerous epidemiological investigations and case studies on survivors who lived through the Holocaust as children or in adulthood, these traumatic experiences are associated with a higher risk for various psychiatric disturbances during the entire life span. Besides the extreme psychological and physical distress during persecution and following traumatisation (parent-child-separation, discrimination while living in other countries) the coping with the trauma and the development of autonomy and ego-strength is additionally impaired by the specific psychodynamics of families with psychologically altered and disturbed parents. OBJECTIVE: What sort of psychodynamic parent-child relationships developed during traumatisation and after the war in subjects currently suffering from chronic impairment of mental health? METHOD: Retrospective analysis of 22 cases with applications for pensions of invalids evaluated by diagnostic categories. RESULTS: The implicit pressure on the children to be sensitive to the needs of their deprived parents places a sense of guilt on their attempts to develop autonomy. The parents were experienced as restrictive or overprotective on the one hand or liable to be rejected or to be intolerant on the other. The suffering and trauma continues to be perceived in family communication to the extent that coping with loss of relatives and the development of independence are impaired. CONCLUSION: The results are discussed critically in terms of current procedures for expertise on pension applications. PMID- 8449477 TI - [Neurologic complications of malaria infection]. AB - Infections with malaria are increasing in Europe and Northern America and are also spreading in tropical endemic areas. A falciparum variety of malaria known as cerebral malaria is the most well-known neurological complication, caused by Plasmodium falciparum and characterised by a fulminant course with disturbances of consciousness and facultative seizures or focal neurological deficits. 50% of deaths caused by malaria are due to cerebral involvement. Pathologically a disseminated vasculomyelinopathic disorder is seen. Immunological changes, vascular-hypoxic disturbances and metabolic-toxic factors contribute to these pathological findings. Facts on diagnostic, differential diagnostic and therapeutic procedures are presented. Beside the severe and life-threatening cerebral malaria some unspecific cerebral symptoms are seen, such as cerebellar ataxia and chorea. Spinal disease and peripheral nerve involvement, polyradiculitis and especially psychiatric disorders have also been described. Every neurological and psychiatric disorder presented first in tropical areas or malaria-endemic regions requires malaria diagnostic tests. In our geographical region, any previous history of a journey to the tropics is an important pointer; in particular, neurological or psychiatric symptoms can be important pointers to malaria. PMID- 8449478 TI - [Psychological disorders after political imprisonment in East Germany--attitude of victims]. AB - In an exploratory study we examined 55 patients who had been politically imprisoned in the GDR for at least six weeks and suffered from enduring mental sequelae of that imprisonment. Views of the patients were assessed by means of standardized open questions and rating scales. Patients reported on stressful conditions in prison, fears concerning the uncertain end of imprisonment, as well as on helpful aspects during and after imprisonment. In a cluster analysis two groups were separated: one group that found social relationships helpful for coping with their experiences and another one that did not feel helped by anybody in coping, 28% of the patients stated that the symptoms were not mainly due to experiences during imprisonment; 20% saw general positive effects of imprisonment on their life. Views of the patients were correlated with other variables such as psychopathological symptoms. The relevance of the findings is discussed briefly. PMID- 8449479 TI - [Delusions of intestinal parasitosis in a female patient with endogenous depression]. AB - A 82-year old woman had, since the age of 50, a history of 9 phases of monopolar endogenous depression with abnormal intestinal sensations and hypochondriac delusions that appeared as delusional parasitosis in 5 of these phases. Differential diagnosis and therapeutic aspects are discussed. PMID- 8449480 TI - Origin and population structure of the Icelanders. AB - The Norse and Celtic contributions to the founding population of Iceland have been estimated previously on a pan-Icelandic basis using gene frequency data for the entire island. Accounts of the settlement of Iceland, however, suggest that different regions received different proportions of Norse and Celtic settlers, indicating the need to incorporate geographic variation into Icelandic admixture studies. A formal likelihood ratio test rejects the null hypothesis of regional homogeneity in admixture proportions. Here, regional admixture estimates for Iceland are reported; they are in agreement with the settlement pattern inferred from historical accounts. The western, northern, and southern regions of Iceland exhibit a moderate Celtic component, consistent with historical indications that these regions were settled by Norse Vikings from the British Isles, accompanied by Celtic wives and slaves. Eastern Iceland, believed to have been settled chiefly by Vikings from Scandinavia, is characterized by a large Norse component of admixture. The northwestern peninsula is also found to be predominantly Norse. Regional genetic data are used to elucidate the contemporary population structure of Iceland. The observed structure correlates well with patterns of Icelandic geography, history, economy, marriage, urbanization, and internal migration. The northeastern region is strongly isolated, the urbanized areas of the north and southwest are representative of the overall population, and the remaining regions exhibit small-scale variation about the genetic central tendency. A high level of genetic homogeneity is indicated (RST = 0.0005), consistent with the high internal migration rate of the Icelanders. A regression of mean per-locus heterozygosity on distance from the gene frequency centroid reveals a greater than average external gene flow into the eastern region, whereas the northwestern peninsula has received less than average external gene flow. Iceland is compared with possible founding populations and was found to have diverged markedly from other northern European countries. PMID- 8449481 TI - Kin-structured migration and isolation by distance. AB - Classical isolation by distance models predict a negative exponential relationship between genetic similarity and geographic distance. Furthermore, under random spatial differentiation all alleles should reflect the same pattern because migration affects all loci identically. The effect of nonrandom composition of migrant groups (kin-structured migration) on these predictions was investigated using computer simulation. Spatial autocorrelation analysis of the simulated gene frequencies showed a decline in similarity with distance in the kin-structured experiments, as predicted by the isolation by distance model. However, the spatial autocorrelations were lower and the variation among correlograms of different alleles was greater than what would be expected under random migration. These findings suggest caution in inferring specific evolutionary conclusions from empirical spatial patterns. PMID- 8449482 TI - Population genetics of apolipoprotein A-4, E, and H polymorphisms in Yanomami Indians of northwestern Brazil: associations with lipids, lipoproteins, and carbohydrate metabolism. AB - Using isoelectric focusing and immunoblotting techniques, we screened 96 serum samples from Yanomami Indians of northwestern Brazil to determine structural variation at three apolipoprotein loci: A4, E, and H. The APO-H locus, which is commonly polymorphic in white and black samples, was found to be monomorphic. At the APO-E locus only two alleles, APOE*3 and APOE*4, rather than the three-allele polymorphism commonly seen in Caucasians, was observed. At the APO-A4 locus no example of the APOA4*2 allele, found in Caucasians, was detected. However, the frequency of the less common APOA4*4 allele was above what has been observed in any other population. We investigated the impact of genetic variation at both polymorphic loci on quantitative differences in lipids, apolipoproteins, serum glucose, glycated hemoglobin, and uric acid. Contrary to the cholesterol elevating effect of APOE*4 reported elsewhere, in both univariate analyses and after adjustments for age, sex, weight, and height, APOE*4 was associated with about a 4% lower mean serum cholesterol. Only after adjustment was this association statistically significant. The APOE*4 allele was significantly associated with unadjusted APO-A1 and APO-E levels but not with any other dependent variable; associations with adjusted APO-A1, APO-C2, and uric acid also approached standard levels of statistical significance (p < or = 0.05). In univariate analyses the APOA4*4 allele was significantly associated with APO-B, serum glucose, percent glycated hemoglobin, and uric acid, but no significant associations were observed after dependent variables were adjusted for age, sex, weight, and height. These results support the notion that apolipoprotein distributions and their associations with lipid and carbohydrate metabolism show ethnic variability. PMID- 8449483 TI - Comparison of structures from frequencies of genes and surnames in the population of Ferrara. AB - The genetic structure based on isonymy and on gene frequencies of 7 enzyme systems was studied in a sample of 1361 individuals residing in the Ferrara Province in the Po delta (northern Italy). The sample was divided into two subsamples. The first, or indigenous, sample (n = 885) was composed of persons born and residing in the same commune of the province; the second, or migrant, sample (n = 476) was composed of persons who immigrated from a different commune. The study of the seven polymorphic genetic systems shows that there is no significant difference in gene and genotype frequencies between the two subsamples. On the other hand, the migration indicator derived from isonymy of family names is significantly larger in the migrant group than in the indigenous group. Isonymy techniques permit the detection of recent migration even under equality of gene frequencies. PMID- 8449484 TI - Pregnancy loss in Nomadic and settled women in Turkana, Kenya: a prospective study. AB - There have been few investigations of intrauterine mortality in non-Western populations that have used techniques capable of detecting early pregnancy loss. We report here the initial results of a prospective study of fetal loss among the Turkana of northwest Kenya. Over 300 nomadic and settled women provided early morning urine samples for 3 consecutive days. Chorionic gonadotropin (hCG), a marker for pregnancy, and markers of ovarian cyclicity (LH, PdG) were determined with solid-phase enzyme immunoassays. Pregnancy was detected in 11% of nomadic women and in 22% of sedentary women of reproductive age. Follow-up surveys revealed that 45% of all pregnancies among settled women were lost; nearly 70% of pregnancies detected in the first trimester were lost. In contrast, none of the nomadic women experienced fetal loss. Because of the small sample sizes, these results must be interpreted cautiously. Nevertheless, even a conservative estimate of the fetal loss rate among the settled women is high compared with Western experience. Anthropometric data suggest that nutritional stress may contribute to the difference between the two populations. There is also some indication that risk of fetal loss in the settled population is associated with parity. The high rate of loss among the settled women along with the difference between the nomadic and settled samples supports the contentions that there may be substantial variation among populations in intrauterine mortality and that the contribution of fetal loss to fertility differences among populations may be more important than has been suspected. PMID- 8449485 TI - Lack of birth seasonality in a nineteenth-century agricultural population: Escazu, Costa Rica. AB - Demographic studies repeatedly indicate that human births tend to fluctuate in a seasonal pattern, particularly in agricultural groups. Interestingly, lack of seasonal variation has been infrequently reported. Recently, Arcury et al. (1990) indicated that only one published study identified a population in which no seasonality of births was demonstrated. Here, I report the results of a historical demographic study that investigates whether Escazu, a nineteenth century population from Costa Rica, experienced birth seasonality. The data set consists of certificates of baptisms from 1851 to 1901 collected at the Parish of San Miguel de Escazu, Costa Rica. The data are an accurate reflection of the actual number of births in the population because even newborn infants who appeared to be in imminent danger of dying (and who subsequently did) were baptized. The baptism series was analyzed by fitting an ARIMA model (0, 1, 1) and cross-correlating it with two climatic series: rainfall and temperature. The autocorrelation analysis of the baptism data fails to demonstrate any cyclical pattern of births in Escazu. Moreover, there is no indication that temperature or rainfall influences the frequency of births. This lack of seasonality is unexpected in an agrarian population such as Ecazu. The results of this analysis indicate that human fertility cycles might not be as prevalent as previously thought. PMID- 8449486 TI - Some factors affecting the secondary sex ratio in a Latin American sample. AB - A sample based on hospital birth records from the Latin American Collaborative Study on Congenital Malformations (ECLAMC) was used in this study. ECLAMC, which covers 11 countries (Uruguay, Chile, Argentina, Brazil, Bolivia, Peru, Paraguay, Ecuador, Venezuela, Colombia, and Costa Rica), registered 1,037,272 live births in the period 1982-1986. We applied several multivariate analysis models to the data and found that the sex ratio was significantly affected by secular, spatial (countries), biological (maternal age, birth order, and ethnic group), and socioeconomic (evaluated by hospital payment) variables. The black ethnic component carried sufficient weight to remove the spatial effect (Brazil and Venezuela) in certain cases. The Amerindian admixture effect on the sex ratio was negative and significant. PMID- 8449487 TI - Odontometry and biological affinity in south Asia: analysis of three ethnic groups from northwest India. AB - Current knowledge of odontometric variation among the people of south Asia is limited, yet variation in tooth size has the potential to answer important questions regarding genetic relationships among contemporary social groups. Here, we report tooth crown diameters for 3 ethnic groups (Bhils, Garasias, Rajputs) from Gujarat State and contrast these data with 10 social groups from north, northwestern, northeastern, west-central, and south India. Univariate descriptive and inferential statistics are presented by group and by sex. Examination of crown diameters demonstrates that tooth size differs significantly between social groups in Gujarat. Cluster analysis of sex-standardized odontometric mean parameter values indicates that in apportionment of tooth size throughout the dentition low-status Garasias are slightly more similar to tribal Bhils than they are to high-status Rajputs. Principal components analysis by sex identifies three components that together account for 58.2% and 56.3% of the total variance among Gujarati females and males, respectively. These components are identified as overall size, a dimensional contrast between mesiodistal diameters and buccolingual diameters, and a dimensional contrast between mesiodistal diameters and buccolingual diameters among anterior teeth coupled with a contrast between anterior teeth (incisors, canines) and posterior teeth (premolars, molars). Ordination of group component scores indicates that (1) males and females of each social group exhibit a pattern of tooth size apportionment most similar to the opposite member of that same social group and (2) low-status Garasias exhibit a tooth size apportionment profile intermediate between tribal Bhils and high status Rajputs. To place this pattern of odontometric variation among modern Gujaratis in larger perspective, data from Gujarati males were contrasted against males from 10 social groups from north, northwestern, northeastern, west-central, and south India. Cluster analysis of group-standardized odontometric mean parameter values indicates that (1) Gujarati social groups, regardless of social status or caste adherence, are more similar to one another than to any other group included in this analysis and (2) Gujarati social groups share closet affinities with geographically proximate social groups (Ahirs, Jats, Kunbis). Principal components analysis yields three components that combine to explain 64.0% of the total variance. These components are interpreted as a dimensional contrast among posterior teeth, a dimensional contrast among nonmolar teeth, and a contrast between anterior and posterior teeth. Ordination of group component scores indicates that tribal Bhils possess tooth size apportionment profiles that are different from other Indian tribal groups but are proximate to those found among Gujarati Hindu groups.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8449488 TI - A PCR-based linkage map of human chromosome 1. AB - A genetic linkage map of human chromosome 1 based entirely on PCR-typable markers has been developed using 38 simple sequence repeat (SSR) polymorphisms. These SSRs include 36 dinucleotide repeats and 2 tetranucleotide repeats. The average heterozygosity at these markers was 0.73 and ranged from 0.52 to 0.95. Multipoint linkage analysis was used to develop a map of these 38 markers in which the relative placement of each locus is supported by likelihood odds > 1000:1. This PCR-based map was anchored at the centromere by the D1Z5 alpha-satellite polymorphism, and the ends of the map were defined by D1Z2 and D1S68, which are the most distal loci in the CEPH consortium map of chromosome 1. The sex averaged, male, and female maps extend for 328, 273, and 409 cM, respectively. The average distance between markers on the sex-averaged map is 8 cM, and the largest interval is 32 cM. This map of highly informative PCR-based markers will provide a rapid means of screening human chromosome 1 for the presence of disease genes. PMID- 8449490 TI - Physical mapping within the tuberous sclerosis linkage group in region 9q32-q34. AB - Pulsed-field gel electrophoresis and flow dot-blot analysis have been used to construct a physical map of the q32-q34 region of chromosome 9, where one of the loci responsible for tuberous sclerosis (TSC1) has been mapped by genetic linkage. Five linked groups of markers have been defined by pulsed-field gel electrophoresis. The orientation of these groups and the order of markers within them were determined by hybridization to flow-sorted dot blots derived from a panel of cell lines of chromosome 9 translocations to place probes proximal or distal to each breakpoint. The local map order in 9q32-q34 derived by application of this combination of techniques is as follows: centromere-ALAD-1.3 Mb-ORM/20 kbD9S16-GSN-250 kb-C5-HXB-1.9 Mb-D9S21-AK1-1.4 Mb-SPTAN1-ASS-800 kb-ABL-2 Mb D9S10/350 Kb/DBH-telomere. PMID- 8449489 TI - Cloning, analysis, and chromosomal localization of Notch-1, a mouse homolog of Drosophila Notch. AB - The Notch gene of Drosophila encodes a large transmembrane protein involved in cell-cell interactions and cell fate decisions in the Drosophila embryo. We report here the isolation of cDNA clones encompassing the full-length coding sequence of Notch-1, a mouse homolog of Drosophila Notch. The predicted amino acid sequence of the Notch-1 protein retains all of the conserved amino acid motifs of Notch and the other vertebrate Notch homologs. The cDNA sequence predicts a 2531-amino-acid protein containing a signal peptide, 36 epidermal growth factor-like repeats, 3 Notch/lin-12 repeats, a transmembrane domain, and 6 cdc10/ankyrin repeats. The Notch-1 gene was localized to the proximal portion of mouse chromosome 2 by mapping with an interspecific backcross panel. PMID- 8449491 TI - Pulsed-field gel electrophoresis and radiation hybrid mapping analyses enable the ordering of eleven DNA loci in Xq22. AB - The Xq22 region of the human X chromosome encompasses the loci of several genes and random DNA markers whose relative positions have not been determined. By a combination of PFGE mapping and the analysis of a selected panel of X chromosome radiation hybrid cell lines, we have constructed physical maps of Xq22 that order a total of 11 polymorphic and nonpolymorphic DNA markers. Ten of these probes have been linked physically into three separate clusters, spanning nearly 6 Mb of DNA in total. The DXS94, DXS147, DXS211, DXS17, and DXS87 loci are all present on a 2.7-Mb MluI fragment; PLP, DXS54, DXS24, and DXS83 are present on MluI fragments spanning over 1.6 Mb; and DXS178 is present on a 1.5-Mb MluI fragment. Mapping with additional enzymes has allowed the further ordering of these loci with respect to each other. Together with these data, analysis of a small set of radiation hybrids has suggested the following over-all order of loci within Xq22: centromere-DXS178-DXS94-DXS147-DXS211-DXS17++ +-DXS87- PLP-DXS54-DXS24-DXS83 COL4A5-telomere. The ordering of these random DNA markers, genes, and disease loci, including the genes responsible for Pelizaeus-Merzbacher disease and Alport syndrome, indicates DNA markers that could be of further use clinically for these diseases. Furthermore, this map should form a basis for the refinement of additional disease-associated loci in this region. PMID- 8449492 TI - Structure and organization of amplified DNA on double minutes containing the mdm2 oncogene. AB - We have been studying a transformed derivative of a mouse fibroblast line (3T3DM) that stably maintains double minute chromosomes (DMs). In this report we describe a comprehensive analysis of the structure of the DMs within this cell line, utilizing a combination of long-range mapping via pulsed-field gel electrophoresis, screening of DM-enriched genomic libraries, and DM sizing using contour-clamped homogeneous electric field (CHEF) gel electrophoresis. Our data indicate that the minute particles in these cells exist as a homogeneous population of circular molecules, roughly 4 Mb in size, upon which three genes are amplified. One of these is the mdm2 oncogene, which has also been found to be amplified in a number of human sarcomas. Further, we present evidence that these three genes are arranged as two identical inverted repeat units linked by spacer regions of heterogeneous size. This work has led to the first model for the structure of an entire double minute particle containing an amplified oncogene; this model provides clues to later events occurring in the gene amplification process in tumor cells. PMID- 8449493 TI - Mus spretus-specific LINE-1 DNA probes applied to the cloning of the murine pearl locus. AB - LINE-1 is the major family of long, interspersed, repetitive DNA sequences found in mammalian genomes. The mouse species Mus spretus contains large LINE-1 subfamilies that are distinguishable from the LINE-1 elements of laboratory Mus domesticus strains by their content of particular nucleotide differences. Oligonucleotides containing these differences act as M. spretus-specific LINE-1 hybridization probes. We have used these probes as a novel genetic tool in conjunction with an interspecific hybrid congenic mouse, in which the M. spretus allele of the pearl gene has been transferred onto a M. domesticus background. From a lambda library prepared from this congenic mouse, four clones were isolated by hybridization to the M. spretus-specific probes. After derivation of genetic markers from these clones, two of them were found to be linked to the pearl gene. These markers are the first two of up to 75 that could be isolated to support cloning the pearl gene. Considering the interspersed nature of LINE-1, we propose that species-specific LINE-1 probes could also be used to isolate markers for many other target genes. PMID- 8449494 TI - Vertical integration of cosmid and YAC resources for interval mapping on the X chromosome. AB - The vertical integration of cosmid and yeast artificial chromosome (YAC) resources is of particular importance in the development of high-resolution maps of selected regions of the human genome. A resource of approximately 95,000 cosmids constructed using DNA from primary fibroblasts of karyotype 49,XXXXX was validated by detailed characterization of a 200-kb cosmid contig spanning exons 8 20 of the dystrophin gene. This resource was used to construct contigs in 0.65 Mb of Xq26 by hybridization of gel-purified YAC DNA to high-density gridded arrays of the cosmid library; positive cosmids were overlapped by finger-printing. Contigs were oriented and ordered relative to existing YACs in the region using cross-hybridization. The overlaps between a representative set of cosmids define 54 intervals of 5-20 kb and were used to construct a high-resolution cosmid interval map of the region, locating markers, dinucleotide repeats, and candidate CpG islands. This approach can be applied rapidly to large regions of the genome and without recourse to subcloning of individual YACs. PMID- 8449495 TI - Provirus-anchored long-range (PAL) mapping of mammalian genomes. AB - To design a strategy for more efficient long-range physical mapping of large mammalian genomes, we have developed a method for directional mapping from anchor points of randomly integrated retroviral proviruses containing sequences that provide unique cleavage sites in the genome. Using this method, we have determined a physical map of approximately 1.6 Mb flanking an Mo MLV-proviral integration site in mouse NIH/3T3 cells. Our results indicate that this provirus anchored long-range (PAL) mapping strategy, which uses only two proviral sequences as universal hybridization probes, can potentially allow rapid construction of physical maps for chromosomal regions devoid of other genetic markers. PMID- 8449496 TI - Theoretical predictions and experimental observations of genomic mapping by anchoring random clones. AB - Genome mapping by anchoring random clones has recently been the subject of intensive theoretical study. In this paper, differences between published predictions of properties of anchored groups of clones ("contigs") are analyzed and simplifications of the mathematical formulae describing these properties are presented. The theoretical predictions are compared with the experimental results from the physical mapping of the genome of Schizosaccharomyces pombe. Information about the number of genome sections with no anchored clone on them ("oceans") and the number of undetected overlaps between the contigs at a given stage of the experiment is required for the decision to change from the random strategy to that of a directed closure of gaps. We demonstrate that the expected number of oceans can be approximated by the number of groups of clones anchored by a single probe ("singletons"), as can the expected number of undetected overlaps between contigs by the number of contigs containing more than one anchor. PMID- 8449497 TI - Sequences homologous to the human X- and Y-borne zinc finger protein genes (ZFX/Y) are autosomal in monotreme mammals. AB - The human zinc finger protein genes (ZFX/Y) were identified as a result of a systematic search for the testis-determining factor gene on the human Y chromosome. Although they play no direct role in sex determination, they are of particular interest because they are highly conserved among mammals, birds, and amphibians and because, in eutherian mammals at least, they have active alleles on both the X and the Y chromosomes outside the pseudoautosomal region. We used in situ hybridization to localize the homologues of the zinc finger protein gene to chromosome 1 of the Australian echidna and to an equivalent position on chromosomes 1 and 2 of the platypus. The localization to platypus chromosome 1 was confirmed by Southern analysis of a Chinese hamster x platypus cell hybrid retaining most of platypus chromosome 1. This localization is consistent with the cytological homology of chromosome 1 between the two species. The zinc finger protein gene homologues were localized to regions of platypus chromosomes 1 and 2 that included a number of other genes situated near ZFX on the short arm of the human X chromosome. These results support the hypothesis that many of the genes located on the short arm of the human X were originally autosomal and have been translocated to the X chromosome since the eutherian-metatherian divergence. PMID- 8449498 TI - Somatic cell hybrid mapping on mouse chromosome 11 (MMU11): assignment of markers relative to two breakpoints in band D. AB - Mouse x rat somatic cell hybrids were generated by fusing mouse cell lines that are heterozygous for reciprocal translocations involving the T42H and T9Ad breakpoints on mouse chromosome 11 (MMU11) to a thymidine kinase-negative (Tk-) rat cell line, RT2Tk-. Selection in HAT medium with geneticin disulfate (G418) resulted in some hybrid clones retaining only one derivative translocation chromosome with that part of MMU11 carrying the Tk-1 locus. Southern blot and PCR analyses of these hybrids were used to map the two breakpoints and 30 markers relative to them. The T42H breakpoint has been localized between Mpo and the Cola 1/Hox-2 cluster of loci and is proximal to the T9Ad breakpoint. The T9Ad breakpoint is proximal to the distal loci Tk-1, Gaa, D11Jkn1, and P4hb. The positions of 14 loci (Hox-2, Cola-1, Rara, Phb, Erba, Rnula-1, D11Pas1, Gfap, D11Mit13, D11Mit11, D11Mit12, Myla, Empb3 and Gh) have been further refined by their localization between the two breakpoints in band D. This study therefore improves the correlation of the genetic and physical maps of MMU11 and extends the known homology between MMU11 and human chromosome 17 (HSA17) by the assignment of three additional HSA17 markers, the profilin gene, Pfn, an anonymous marker, D17s28h, and the Crk oncogene, to above the T42H breakpoint; and the prohibitin gene, Phb, to between the T42H and T9Ad breakpoints in band D on MMU11. PMID- 8449499 TI - Irradiation hybrids for human chromosome 11: characterization and use for generating region-specific markers in 11q14-q23. AB - High-dose irradiation hybrids containing fragments of chromosome 11 have been generated, with a view to isolating new region-specific markers. Forty-seven lines were scored for 34 markers: average retention was 6%. Fourteen lines contain markers from 11q14 to 11q23. One of these, Jo12, has 11q markers extending from tyrosinase (q14-q21) to PBGD (q23.3) plus one marker (TYRL, p11.2) from 11p. In situ hybridization using Alu PCR products from Jo12 as probe confirmed that the human DNA is derived from two regions, one in proximal 11p and a second, larger region in 11q23. Plasmid libraries of Alu PCR products from this and three other hybrids have been made. Six of eight recombinants identified as having single-copy inserts were mapped back to the regions of 11q22-q23 detected in the originating hybrid; only one mapped to a region not originally detected, and one was of hamster origin. These six clones provide new markers in 11q22-q23 that can be used directly for polymorphism studies. This series of hybrids is therefore a valuable resource for the rapid generation of markers from specific, defined regions of chromosome 11. PMID- 8449500 TI - Linkage analysis and physical mapping near the gene for X-linked agammaglobulinemia at Xq22. AB - The gene for X-linked agammaglobulinemia (XLA) has been mapped to Xq22. No recombinations have been reported between the gene and the probe p212 at DXS178; however, this probe is informative in only 30-40% of women and the reported flanking markers, DXS3 and DXS94, are 10-15 cM apart. To identify additional probes that might be useful in genetic counseling, we examined 11 polymorphisms that have been mapped to the Xq21.3-q22 region in 13 families with XLA. In addition, pulsed-field gel electrophoresis and yeast artificial chromosomes (YACs) were used to further characterize the segment of DNA within which the gene for XLA must lie. The results demonstrated that DXS366 and DXS442, which share a 430-kb pulsed-field fragment, could replace DXS3 as proximal flanking markers. Probes at DXS178 and DXS265 identified the same 145-kb pulsed-field fragment, and both loci were contained within a 200-kb YAC identified with the probe p212. A highly polymorphic CA repeat (DXS178CA) was isolated from one end of this YAC and used in linkage analysis. Probes at DXS101 and DXS328 shared several pulsed-field fragments, the smallest of which was 250 kb. No recombinations were seen between XLA and the DXS178-DXS265-DXS178CA complex, DXS101, DXS328, DXS87, or the gene for proteolipid protein (PLP). Key crossovers, when combined with the linkage data from families with Alport syndrome, suggested the following order of loci: cen-DXS3-DXS366-DXS442-(PLP, DXS101, DXS328, DXS178-DXS265-DXS178CA complex, XLA) (DXS87, DXS94)-DXS327-(DXS350, DXS362)-tel.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8449501 TI - Three Hsp70 genes are located in the C4-H-2D region: possible candidates for the Orch-1 locus. AB - The central region of the mouse MHC harbors a recombinational hot spot area. Most recombinations in this part of the complex take place between the Hsp70.1 gene and the G7 gene. This interval is of interest since structurally indistinguishable recombinant haplotypes do differ in functional behavior. Susceptibility to experimental allergic orchitis, which is controlled by the Orch 1 locus, is one example. We have analyzed the hot spot region at the molecular level in order to understand the molecular organization of this chromosomal segment. From a C57BL genomic library we constructed a cosmid contig bridging the interval between Hsp70.1 and G7. The Orch-1 gene maps to a 60-kb segment of DNA in which we found a new Hsp70 homologue, Hsp70.3. Thus, as in the human MHC, the central region of the mouse MHC harbors a cluster of three Hsp70 genes; Hsp70.1, Hsp70.3, and Hsc70t. Two other genes are located in this critical interval (G7b and G7a/Bat-6), and there might still be other undetected genes present in the region. Heat shock proteins play an important role in a large number of physiological processes and it is tempting to speculate that Hsc70t, which exhibits testis-specific expression, may be identical to Orch-1. PMID- 8449502 TI - Refinement of the spinal muscular atrophy locus to the interval between D5S435 and MAP1B. AB - The childhood-onset SMA locus has been mapped to chromosome 5q13, in a region bounded by the proximal locus, D5S6, and the closely linked distal loci, D5S112 and MAP1B. We now describe a highly polymorphic, tightly linked microsatellite marker (D5S435) that is very likely the closest proximal marker to the SMA locus. Multipoint linkage analysis firmly establishes the following order of markers at 5q13: centromere-D5S76-D5S6-D5S435-MAP1B/D5S112- D5S39-telomere. The data indicate that SMA resides in an approximately 0.7-cM (range 0.1-2.1) region between D5S435 and MAP1B. This finding reduces by approximately fourfold the genetic region that most likely harbors the SMA locus and will facilitate the physical mapping and cloning of the disease gene region. PMID- 8449503 TI - Heteroduplex analysis can increase the informativeness of PCR-amplified VNTR markers: application using a marker tightly linked to the COL2A1 gene. AB - Variable number of tandem repeat (VNTR) polymorphisms provide a high degree of informativeness in linkage studies. Whether performed by standard methods or by polymerase chain reaction (PCR), analysis of these markers involves assessment of the length of each allele. VNTR alleles usually differ in the number of tandem repeats. During PCR amplification of a VNTR closely linked to the type II collagen gene (COL2A1), we identified allelic microheterogeneity through the analysis of unique heteroduplexes between amplified strands of the two alleles. In one large pedigree, heteroduplex analysis identified six COL2A1 alleles; standard methods would have identified only three distinct alleles. The identification of these heteroduplexes allowed the determination of the COL2A1 inheritance pattern in the family, which otherwise would have been noninformative. PMID- 8449504 TI - STS map of genes and anonymous DNA fragments on human chromosome 18 using a panel of somatic cell hybrids. AB - Somatic cell hybrids containing different deleted regions of chromosome 18 derived from patients with balanced translocations or terminal deletions were used to create a deletion mapping panel. Twenty-four sequence-tagged sites (STSs) for 17 genes and 7 anonymous polymorphic DNA fragments were identified. These STSs were used to map the 24 loci to 18 defined regions of chromosome 18. Both ERV1, previously mapped to 18q22-q23, and YES1, previously mapped to 18q21.3, were found to map to 18q11.21-pter. Several genes previously mapped to 18q21 were found to be in the order cen-SSAV1-DCC-FECH-GRP-BCL2-PLANH2-tel. The precise mapping of genes to chromosome 18 should help in determining whether these genes may be involved in the etiology of specific chromosomal syndromes associated with chromosome 18. The mapping of the polymorphic loci will assist in the integration of the physical map with the recombination map of chromosome 18. PMID- 8449505 TI - Spectrum of mutations in CRM-positive and CRM-reduced hemophilia A. AB - Hemophilia A is due to the functional deficiency of factor VII (FVIII, gene locus F8C). Although half the patients have no detectable FVIII protein in their plasma, the more rare patients (approximately 5%) have normal levels of a dysfunctional FVIII and are termed cross-reacting material (CRM)-positive. More commonly (approximately 45%), patients have plasma FVIII protein reduced to an extent roughly comparable to the level of FVIII activity and are designated CRM reduced. We used denaturing gradient gel electrophoresis to screen for mutations within the F8C gene of 11 patients (6 CRM-positive, 5 CRM-reduced) and identified 9 different mutations in 9 patients after analyses of all 26 exons, the promoter region, and the polyadenylation site. Six mutations have not been described previously. Five were missense (Ser289Leu, Ser558Phe, Val634Ala, Val634-Met, Asn1441Lys), and the sixth was a 3-bp deletion (delta Phe652). A review of the literature and the assay of FVIII antigen in 5 hemophilia A patients with previously identified missense mutations from this laboratory yielded a total of 20 other unique CRM-reduced and CRM-positive mutations. Almost all CRM positive/reduced mutations (24/26) were missense, and many (12/26) occurred at CpG dinucleotides. We examined 19 missense mutations for evolutionary conservation using the portions of the porcine and murine F8C sequences that are known, and 18/19 amino acid residues altered by mutation in these patients were conserved. Almost 50% of mutations (11/26) clustered in the A2 domain, suggesting that this region is critical for the function of FVIII.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8449506 TI - A large duplication in the gene for lysyl hydroxylase accounts for the type VI variant of Ehlers-Danlos syndrome in two siblings. AB - Ehlers-Danlos syndrome is a heterogeneous disorder characterized by joint hypermobility, skin hyperextensibility, fragility, and other signs of connective tissue involvement. In addition to these, the type VI variant of the disease has some special characteristics such as kyphoscoliosis and ocular abnormalities. The biochemical abnormality in most patients with this autosomal recessively inherited type VI variant is a deficiency in the activity of lysyl hydroxylase (EC 1.14.11.4), the enzyme catalyzing the formation of hydroxylysine in collagens and other proteins with collagen-like amino acid sequences. The type VI variant of Ehlers-Danlos syndrome was first identified in two sisters with a reduced amount of lysyl hydroxylase activity in their skin fibroblasts (S.R. Pinnell, S. M. Krane, J. E. Kenzora, and M. J. Glimcher (1972) N. Engl. J. Med. 286: 1013 1020). Our recent molecular cloning of lysyl hydroxylase has now made it possible to study the mutations leading to the deficiency in lysyl hydroxylase activity in these cells. Our data indicate that the mRNA for lysyl hydroxylase produced in the affected cells is about 4 kb in size, whereas it is 3.2 kb in the control cells. The sequencing of the cDNA for lysyl hydroxylase from the affected cells revealed an apparently homozygous duplication rearrangement of nucleotides 1176 to 1955, corresponding to amino acids 326 to 585 in the normal sequence. From Southern blotting data, the duplicated area in the gene equals about 6-9 kb and corresponds to seven exons. PMID- 8449507 TI - Localization of a highly conserved human potassium channel gene (NGK2-KV4; KCNC1) to chromosome 11p15. AB - Several genes (the Shaker or Sh gene family) encoding components of voltage-gated K+ channels have been identified in various species. Based on sequence similarities Sh genes are classified into four groups or subfamilies. Mammalian genes of each one of these subfamilies also show high levels of sequence similarity to one of four related Drosophila genes: Shaker, Shab, Shaw, and Shal. Here we report the isolation of human cDNAs for a Shaw-related product (NGK2, KV3.1a) previously identified in rat and mice. A comparison of the nucleotide and deduced amino acid sequence of NGK2 in rodents and humans shows that this product is highly conserved in mammals; the human NGK2 protein shows over 99% amino acid sequence identity to its rodent homologue. The gene (NGK2-KV4; KCNC1) encoding NGK2 was mapped to human chromosome 11p15 by fluorescence in situ hybridization with the human NGK2 cDNAs. PMID- 8449508 TI - Localization of the 70-kDa peroxisomal membrane protein to human 1p21-p22 and mouse 3. AB - The 70-kDa peroxisomal membrane protein (PXMP1) is a member of the ATP-binding cassette transporter family. In humans, mutations in this gene may be responsible for a subset of patients with Zellweger syndrome, a lethal inborn error of peroxisome assembly. The PXMP1 gene was assigned to human chromosome 1p21-p22 by in situ hybridization and its murine homologue (Pxmp-1) to chromosome 3 by interspecific backcross analysis. PMID- 8449509 TI - Orphan peak analysis: a novel method for detection of point mutations using an automated fluorescence DNA sequencer. AB - Automated DNA sequencers draw the four-base profiles of a sample with four different colors, but it is also possible to draw the profiles of a base-specific reaction of four different samples with four colors. PCR-amplified DNAs from four individuals were subjected to a single base-specific sequencing reaction and the products were applied to a set of four lanes of an automated DNA sequencer. A base substitution in an individual was clearly identified as an individual specific peak with a color specific for the individual. In this way, we analyzed more than 50 individuals and identified several polymorphic base substitutions. The sensitivity of this method was high enough to allow detection of the mutation/polymorphism even if samples from several individuals were applied to one lane. Thus, our method is applicable to screening of a large number of samples in an automated manner. PMID- 8449510 TI - Two members of the S-lac lectin gene family, LGALS1 and LGALS2, reside in close proximity on human chromosome 22q12-q13. AB - S-lac lectins are a family of soluble lactose-binding proteins thought to function in the control of cell growth. We now report the chromosomal mapping of two members of the family, termed L-14-I and L-14-II, to the q12-q13 region of human chromosome 22, suggesting the possibility of a cluster of genes for lactose binding proteins. PMID- 8449511 TI - Assignment of the mouse tartrate-resistant acid phosphatase gene (Acp5) to chromosome 9. AB - Tartrate-resistant acid phosphatase is a marker enzyme for osteoclasts, the multinucleated cell responsible for bone resorption. Interspecific somatic whole cell hybrids and karyotypically simple microcell hybrids were used to map the gene encoding tartrate-resistant acid phosphatase (Acp5) to mouse Chromosome 9. Acp5 is therefore a member of a syntenic family of genes that map to human chromosome 19p13.1-p13.3 and mouse Chromosome 9. PMID- 8449512 TI - A pulsed-field gel electrophoresis (PFGE) map of twelve loci on chromosome 11q11 q13. AB - We report a pulsed-field gel electrophoresis map of 12 loci on proximal human chromosome 11q. Linkage studies have shown that this region of chromosome 11 contains the genes for familial atopic disease (APY) and multiple endocrine neoplasia type I (MEN1) (4). A physical map containing polymorphic loci will aid in the isolation of these disease genes. The map reported here has two noncontiguous groups of loci accounting for 8 of the 12 loci evaluated. One group spans a maximum distance of 1600 kb and includes D11S146, BCL1, PRAD1, INT2, and HSTF1. The other group includes FTH1, C1NH, and COX8. TCN1, PGA, and PYGM did not yield any comigrating fragments and could not be physically linked on this PFGE map. These data enhance previously published physical maps of proximal 11q by refining the localization of and distances between markers in the BCL1 region. Additionally, new information about the locations and physical relationships between FTH1, C1NH, and COX8 is presented. PMID- 8449513 TI - Localization of the CYP2D gene locus to human chromosome 22q13.1 by polymerase chain reaction, in situ hybridization, and linkage analysis. AB - Using a combination of somatic cell hybrids, in situ hybridization, and linkage mapping, we have been able to localize the cytochrome P450 CYP2D6 gene to chromosome 22 in the region q13.1. Linkage analysis, using locus-specific primers, showed a maximum sex-average lod score of 8.12 (theta = 0.00) between the marker pH130 (D22S64) and CYP2D6, of 6.92 (theta = 0.00) between the marker KI839 (D22S95) and CYP2D6, and of 4.80 (theta = 0.036) between the platelet derived growth factor beta subunit gene (PDGFB) and CYP2D6. PMID- 8449514 TI - Optimization of microsatellite analysis for genetic mapping. AB - A method for typing microsatellite polymorphisms is described. It involves amplification using the polymerase chain reaction with one primer 5' end-labeled with 32P. Alleles are separated by denaturing gel electrophoresis and detected by autoradiography. Standardized conditions allow accurate typing of almost all microsatellite polymorphisms, and results are usually obtained within 24 h. PMID- 8449515 TI - Comparative mapping on the mouse and human X chromosomes of a human cDNA clone encoding the vasopressin renal-type receptor (AVP2R). AB - Mutations in the gene for the human renal-type vasopressin receptor (V2R) have recently been identified in patients with nephrogenic diabetes insipidus (NDI). Both V2R and NDI have been independently mapped to Xq28. Using a combination of genetic and physical mapping, we have localized the murine V2r locus to within 100 kb of L1Cam on the mouse X chromosome in a region syntenic with human Xq28. Based on conserved gene order of mouse and human loci in this region, physical mapping using DNA derived from human lymphoblasts has established that the corresponding human loci V2R and L1CAM are linked within 210 kb. The efficiency and precision of genetic mapping of V2r and other loci in the mouse suggest that it might be easier to map additional human genes in the mouse first and infer the corresponding human location. More precise physical mapping in man could then be performed using pulsed-field gel electrophoresis and/or yeast artificial chromosomes. PMID- 8449516 TI - Chromosomal reassignment: YACs containing both YES1 and thymidylate synthase map to the short arm of chromosome 18. AB - The YES1 proto-oncogene was mapped previously to human chromosome band 18q21.3 by using isotopic in situ hybridization. Using yeast artificial chromosomes (YACs) as probes and fluorescence in situ hybridization, a strong signal was detected in the region corresponding to 18p11.3. Restriction digests confirmed that the YACs contained the YES1 gene and not other cross-hybridizing, protein-tyrosine kinases. In addition, these YACs were found to contain another 18p11.32 gene, thymidylate synthase. These genes were less than 50 kb apart. Collectively, these data suggest that YES1 maps to 18p11.32 rather than to 18q21.3. PMID- 8449517 TI - Characterization and polymerase chain reaction (PCR) detection of an Alu deletion polymorphism in total linkage disequilibrium with myotonic dystrophy. AB - The mutation causing myotonic dystrophy has been identified as an unstable trinucleotide CTG repeat located in the 3' untranslated region of a gene putatively encoding a serine-threonine protein kinase. The mutation has been reported to be in total linkage disequilibrium with an insertion/deletion polymorphism located within the kinase gene. To determine the nature of this polymorphism, we have sequenced this genomic fragment and have found that the sequence of this region consists of five consecutive Alu repeats. Further analysis suggests that the smaller of two alleles is actually due to a proposed deletion event that resulted in the loss of an equivalent of three Alu repeats. We have developed a PCR-based assay to detect this polymorphism, the closest, distal marker to the DM mutation. PMID- 8449518 TI - Human somatostatin receptor genes: localization to human chromosomes 14, 17, and 22 and identification of simple tandem repeat polymorphisms. AB - The genes encoding three different human somatostatin receptor subtypes, designated SSTR1, SSTR2, and SSTR3, were mapped to chromosomes 14, 17, and 22, respectively, by analyzing their segregation in a panel of reduced human-hamster somatic cell hybrids. These assignments were confirmed independently using fluorescence in situ hybridization to metaphase chromosomes and the genes were further localized to 14q13, 17q24, and 22q13.1, respectively. Highly informative simple tandem repeat DNA polymorphisms were identified in SSTR1 and SSTR2. PMID- 8449519 TI - Generation of ordered phage sublibraries of YAC clones: construction of a 400-kb phage contig in the human dystrophin gene. AB - A phage contig of 400 kb that extends from the brain-specific promoter at the 5' end of the human dystrophin gene, through the muscle-specific promoter over 100 kb further downstream, and across most of intron 1 has been assembled. To achieve this, a yeast artificial chromosome (YAC) subcloning approach was used. Total DNA from a yeast strain containing a 400-kb YAC from the dystrophin gene was cloned using a lambda phage vector containing RNA polymerase promoters flanking the cloning sites. Phage containing human DNA inserts were then ordered into an overlapping set by hybridization of end-specific RNA probes from individual clones back to plaque lifts of gridded phage subclones. The clones generated will be useful as reagents for detailed structural and functional analyses of this region of the dystrophin gene. PMID- 8449520 TI - Chromosomal organization of the inducible and constitutive prostaglandin synthase/cyclooxygenase genes in mouse. PMID- 8449521 TI - Assignment of the gene encoding glycogen synthase (GYS) to human chromosome 19, band q13.3. PMID- 8449522 TI - Assignment of the human carboxypeptidase E (CPE) gene to chromosome 4. PMID- 8449523 TI - Assignment of human potassium channel gene KCNA4 (Kv1.4, PCN2) to chromosome 11q13.4-->q14.1. PMID- 8449524 TI - Autosomal dominant retinitis pigmentosa: a novel mutation at the peripherin/RDS locus in the original 6p-linked pedigree. PMID- 8449525 TI - A Heideggerian hermeneutical analysis of survivors of incest. AB - The phenomenological study described in this paper examined the lived experience of adult women survivors of childhood incest. Self-identified incest survivors (N = 5) participated in non-structured, audiotaped interviews. Subsequent transcripts were analyzed by a team of researchers using Heideggerian phenomenology to identify common meanings and themes in the texts. The major findings of the study suggested two constitutive patterns of lived experience among incest survivors: "Remembering As a Coming of What Has Been" and "Care: Reconstituting a Sense of Me." PMID- 8449526 TI - Effects of slow stroke back massage on relaxation in hospice clients. AB - This study was done to investigate a nonpharmacological means of relaxation with 30 hospice clients. The purpose was to examine the effects of slow stroke back massage (SSBM) on systolic and diastolic blood pressure, heart rate and skin temperature. SSBM was associated with decreases in systolic BP, diastolic BP, and heart rate and with an increase in skin temperature. SSBM was shown to produce modest clinical, but statistically significant changes in vital signs which were indicative of relaxation. It is a cost-effective treatment which adds to the comfort of hospice clients. PMID- 8449527 TI - Determinants of health-promoting lifestyles in older persons. AB - The purpose of this study was to determine the degree to which selected components derived from Pender's Health Promotion Model (1982) explained engaging in health promotion practices in a sample of 477 persons 65 years and older. One directional hypothesis was tested using canonical correlation analysis. Three significant canonical variates were demonstrated, explaining 88.7 percent of variance. Older healthy persons with high self-esteem and internal locus of control reported practicing five of the six health promotion strategies. Men with higher income and self-esteem but poorer health less often exercised or ate well. Older married subjects with higher incomes who were internally controlled were more likely to engage in exercise, health responsibility and stress management but not in interpersonal support. Findings provide direct multivariate support for the additive nature of the relationships posited in the Health Promotion Model. PMID- 8449528 TI - Coping strategies of abstainers from alcohol up to three years post-treatment. AB - This study characterizes the experiences and coping strategies of 23 alcohol dependent persons who maintained abstinence from alcohol use up to three years post-treatment. Interview, journal, and mail questionnaire data were collected at 12, 18 and 36 months post-treatment. The results support and extend the theoretical model of change proposed by Prochaska and DiClemente (1984). Hallmarks of successful change included factors that can be learned, practiced, perfected and are transferable to other alcohol-dependent persons who decide to break the addictive cycle. PMID- 8449529 TI - Gossip: does it play a role in the socialization of nurses? AB - Despite its generally negative reputation, gossip continues to be a significant genre of communication in every society. The initial purpose of this paper is to scrutinize gossip from historical, analytical and feminist perspectives. An extensive review of the literature suggests gossip serves three primary functions: information, influence or social control and entertainment. The second purpose is to explore how the functions of gossip may contribute to the socialization of nurses to their professional role and to their work culture. PMID- 8449530 TI - The idea of history and the history of ideas. AB - Professional nurses understand that the historian's task is to inquire into the issues and ideas of nursing's past, but may not comprehend the nature and methods of historical research. Although historical research is similar to other qualitative methods, the results are usually presented in the form of "story." The story, called the historical narrative, is intended to enlighten the reader but it may disguise the historian's method and mislead the reader into thinking that historical method is either non-existent, simple or non-important. The purpose of this article is to begin a dialogue which will negate the myths that historical method is neither rigorous nor significant and to encourage other nurse historians into articulating, sharing and teaching others "how historians think." PMID- 8449531 TI - Anticipatory guidance of parents of new infants: potential contribution of the internal working model construct. AB - Although anticipatory guidance for parents of young children has been well subscribed to as a clinical strategy for over half a century, it has little theoretical substance to guide its practice and to direct research that would develop and test the practice. The assumptions and definitions of the traditional practice of anticipatory guidance focus on providing information about what to expect and how to deal with unwanted or challenging events or conditions related to developmental or life change. In this paper, the potential contributions of social cognition theory, including the construct of internal working models, to the theory of anticipatory guidance are explored and implications of the revised theory are illustrated. PMID- 8449532 TI - Patients' responses to postponement of coronary artery bypass graft surgery. AB - The purpose of this study was to determine the thoughts and feelings of patients (n = 24) awaiting coronary artery bypass graft (CABG) surgery and, in particular, the thoughts and feeling of those patients (n = 17) whose surgical procedure was postponed. On average these patients waited four additional days before the surgery could be performed. Patients reported that the most difficult part of CABG surgery was the wait itself. Those whose CABG surgery was postponed expressed anger and disappointment, had additional tests, procedures and medication, extended hospital stays and increased costs. PMID- 8449533 TI - The contribution of nursing theory to nursing administration practice. AB - The requisite theoretical base of nursing administration has been defined as a synthesis of knowledge from nursing and other disciplines. The purpose of this paper is to explore the contribution made by nursing knowledge to the distinctive epistemology of nursing administration. The value of nursing theory to administration practice is articulated as well as levels of theory development and their relationship to the knowledge base of nursing administration practice. PMID- 8449534 TI - Rosemary Ellis' views on the substantive structure of nursing. AB - According to the late Rosemary Ellis, the most pressing priority of nursing scholars is to explicate the substantive structure of our discipline. Drawing largely from her unpublished work, this paper summarizes the views of Ellis on the nature of nursing's substantive structure and raises implications for the development of nursing theory. PMID- 8449535 TI - The roles and functions of clinical nurse specialists. AB - This paper examines the research conducted on the role and function of Clinical Nurse Specialists (CNS). Four research themes have evolved over the past few decades: perceptions of the role; CNS' time allocation; effects of CNS on patient and family outcomes and cost of care; and, the actual functions of CNS. The authors identify areas for future research to demonstrate the differences that CNS make in health outcomes. PMID- 8449536 TI - Health policy dilemmas related to high technology infertility services. PMID- 8449538 TI - On the dangers of invisibility. PMID- 8449537 TI - Health policy dilemmas related to high technology infertility services. PMID- 8449539 TI - Contranidatory activity of early luteal phase administration of mifepristone in the rhesus monkey. AB - The contranidatory action of mifepristone (RU 486) given as a single application at different dosages to mated rhesus monkeys (Macaca mulatta) on second day after ovulation has been examined in the present study. In group 1, monkeys (n = 3) received only vehicle (benzyl benzoate: olive oil, 1:4, v/v) and were treated as controls. In group 2 monkeys (n = 4), RU 486 was given by gavage at 10 mg/kg in group 4 (n = 5). The patterns of cycles and profiles of serum estrogen and progesterone were monitored for assessing the occurrence of implantation and pregnancy. At a single dose of 10 mg/kg, RU 486 was found to be ineffective in preventing nidation, resulting pregnancy in three females out of four treated monkeys. Similarly, an s.c. administration of 1 mg/kg could provide pregnancy protection in two of the four treated monkeys. In these monkeys, however, the menstrual cycle characteristics were not affected as compared to pretreatment cycles. Interestingly, the administration of 2 mg/kg, s.c., RU 486 could provide a hundred percent pregnancy protection in mated monkeys, and there was no significant changes in the pattern of menstrual cycle characteristics. It appears that an early post-ovulatory administration of RU 486 may be successfully used in human as an effective once-a-month, early luteal phase contranidatory agent. PMID- 8449540 TI - Urinary bladder serosal chemoreceptor induced cardio-respiratory responses: possible pathway. AB - There is limited experimental information about pain originating from the urinary bladder. In the present study application of 3-5 ml of 1% ammonium oxalate, 1% potassium chloride, 100m M citric acid, IM ammonium chloride, 1% oxalic acid, 0.5% sodium hydroxide, or 2 micrograms/ml bradykinin, to the serosal surface of the urinary bladder in anaesthetized dogs, resulted in an increase in heart rate, rise of both systolic and diastolic blood pressures and increase in respiratory rate and depth. These facilitatory cardio-respiratory responses were coupled with powerful contractions of the urinary bladder wall. By contrast, mucosal application of the chemicals did not bring about any significant change. The cardio-respiratory responses obtained were completely abolished on serosal application of procaine (1%), section of the hypogastric nerves or by spinalectomy at T8. Bilateral cervical vagotomy and pelvic nerve section did not modify the responses. However, the blood pressure responses were abolished by the administration of tolazoline hydrochloride, indicating a major role of sympathetics in this nociceptive reflex. PMID- 8449541 TI - Toxicology of lead: some recent observations. PMID- 8449542 TI - The effect of bilateral gastric vagotomy and histamine stimulation on parietal cell activity in streptozotocin induced diabetic rat model. AB - Disturbances in gastric secretions are commonly associated with diabetes mellitus and are usually attributed to autonomic neuropathy. Systematic documentation of the effects of experimental diabetes on parietal cell functions are not available. This study has been designed to evaluate the acid secretory status of the parietal cells in streptozotocin (STZ) induced rat model of diabetes mellitus by assessing the effect of bilateral gastric vagotomy and histamine administration on them. Results show that bilateral gastric vagotomy in the control rats as well as in experimental diabetes lowers the acid secreting capacity of the parietal cells. In the diabetic rats, however, vagotomy does not further decrease the gastric acid secretion. Histamine stimulation augments the acid secretory response in the controls but this rise is substantially prevented in the diabetic state. Histamine challenge following vagotomy in normal controls elicits a sharp rise in gastric acid secretion though not to the same extent as seen in rats with intact vagi. In the diabetic rats however, histamine fails to augment acid secretion after vagotomy. Diabetes is thus seen to severely impair the acid secretory response of the parietal cells and their responsiveness to histamine. PMID- 8449543 TI - Role of caudate nucleus on modulation of blood pressure responses in cat. AB - Changes in blood pressure, heart rate and respiration were studied in 15 cats on bilateral stimulation of rostral, middle and caudal regions of caudate nucleus. Hypotensive response was obtained on stimulation of anterior caudate nucleus, which changed to pressor response when posterior caudate nucleus was stimulated. Biphasic blood pressure responses were recorded on stimulation of middle caudatal area. No detectable changes were observed on heart rate and respiration. This suggests a role for caudate nucleus as a modulator in blood pressure regulation. PMID- 8449544 TI - Energy expenditure and ventilatory responses during Virasana--a yogic standing posture. AB - Energy expenditure and ventilatory responses to yogic standing posture of Virasana were studied on 10 healthy men (25-37 years of age). The results of various responses respectively to the horizontal supine, Chair-sitting and Virasana were: Minute Ventilation (VE) 7.64, 8.61 and 18.67 L/min; Respiratory Frequency (FR) 15.71, 15.70 and 21.45 Breath/min; Tidal Volume (VT) 0.496, 0.544 and 0.827 L/min; Oxygen consumption (VO2) 0.127, 0.234 and 0.573 L/min; Carbondioxide Elimination (VCO2) 0.127, 0.134 and 0.420 L/min; Respiratory Exchange Ratio (RER) 0.58, 0.57 and 0.69; Heart Frequency (FH) 65.2, 74.5 and 104.4 beats/min; Oxygen Pulse (O2P) 3.32, 3.17 and 5.45 ml/beat; Ventilatory Equivalent (VE-EQ) 36.78, 37.12 and 33.85; Multiple of Resting VO2 (METS) 0.96, 1.05 and 2.53 and Metabolic Cost (MC) 1.04, 1.13 and 2.76 Cal/min. Virasana posture was characterised by higher VE, FR, VT, VO2, VCO2, FH and O2P with lesser VE-EQ. The observations suggest that Virasana induces temporarily a hypermetabolic state characterised by enhanced sympathetic nervous system activity which gets inhibited during the adoption of resting supine shavasana posture. PMID- 8449545 TI - P3 event related cerebral evoked potential in chronic pain patients. AB - P3 component of event related cerebral evoked potentials has been applied as an index of information processing in a wide variety of normal and cognition impaired subjects. The present study was undertaken to examine possible changes in central nervous system processing and subjective appraisal, indexed by cerebral evoked potentials (N200 & P300), in 20 pain free controls and 20 subjects suffering from chronic pain (cervical spondylosis and low backache, sciatica). Standard auditory 'Odd ball' paradigm involving simple discrimination task of concentrating on infrequent (target) stimulus and ignoring the frequent stimulus (non-target) was employed. Evoked response trial of discriminating 32 target stimuli out of 160 total presented (20% target and 80% non target, randomly) were replicated and analysed by computer. There was significant increase in P3 latency in patients suffering from pain as compared to age and sex matched controls, suggesting change in cognitive functions. PMID- 8449546 TI - Autonomic functions during different phases of menstrual cycle. AB - Autonomic functions were studied in female healthy human subjects during the pre menstrual, menstrual and post-menstrual phases. Our findings indicate a higher BP (systolic) and lower GSR in pre-menstrual phase as compared to other phases. Parasympathetic activity on the other hand does not show significant differences. PMID- 8449548 TI - Effect of IUCD on human uterine fluid protein concentration throughout the menstrual cycle. AB - Uterine fluid of 96 Women implanted with IUCD was collected and processed for protein estimation. The results obtained in women having IUCD were compared with those of parous/normal women. The trend of fluctuation in protein concentration was the same in both parous and women with IUCD. But comparatively the protein concentration in it was so much higher in women having IUCD throughout the menstrual cycle. The increased concentration may be responsible for making the fluid environment unfavourable for blastocyst as well as sperm metabolism. PMID- 8449547 TI - The effect of capsaicin on the small intestinal absorption of glucose and alanine in the rat. AB - Chilli (containing the active ingredient capsaicin) forms an important flavouring agent in the preparation of meals in the tropics. Previous studies have shown that capsaicin in high doses causes gross structural and functional changes in the gut. The present study investigates the effect of pure capsaicin on the absorption of glucose, water and alanine by the small intestine of the rat. Perfusion studies were carried out using a 10 cm jejunal segment. Absorption rates of glucose, water and alanine from a control solution containing the nutrient and from a test solution containing added capsaicin were compared. Recovery of absorptive function of the intestinal mucosa after exposure to capsaicin was also studied. Absorption of water, glucose and alanine was found to be significantly reduced in the presence of capsaicin. Recovery of absorptive function occurred when capsaicin was withdrawn from the perfusate. It was concluded that capsaicin adversely affected absorption of nutrients from the rat small intestine; this effect was reversible at least in the case of some nutrients. PMID- 8449549 TI - Adverse reactions to propranolol, a non-selective beta-adrenergic blocking agent in hypertensive patients--a collaborative study. AB - Propranolol, a nonselective beta-adrenergic blocking agent, although prescribed frequently, has not been monitored for its adverse reactions in Indian population. A collaborative ADR monitoring study was planned in 2661 hypertensive patients. Exclusion criteria were associated circulatory insufficiency, heart block, left ventricular failure, diabetic mellitus and airway obstruction. The incidence of ADR was 2.1%, which is lower than reported incidence of 8.7 to 43.7 percent in other studies. This could be attributed to improper selection of patients, differences in methodology of monitoring, or to racial variation. In the present study ADR of fatigue (1.1%), dizziness (0.4%) and headache (0.2%) constituted the bulk. Additional reaction of pain in chest (0.2%), heart block (0.1%), hypoglycemia (0.1%), loss of libido (0.1%) and shock (0.03%), were also observed. PMID- 8449550 TI - Serum level of iron and transferrin in normal and anaemic pregnant women. AB - Serum levels of iron and transferrin, and percent saturation of total iron binding capacity (TIBC) and latent iron binding capacity were estimated in 89 women in their I, II and IIIrd trimester of pregnancy. Associated infective, metabolic or degenerative diseases were excluded after clinical examination. The women were divided into three groups of normal, mildly anaemic and severely anaemic. In the normal group serum iron levels were within normal range irrespective of period of gestation, whereas in the anaemic groups, these were lower. Serum transferrin levels were significantly low in II and III trimester of pregnancy of anaemic women. Percent saturation of TIBC was even lower than normal in Ist trimester of pregnancy in normal pregnancy (27.12%). However in mild anaemic there was significant fall and in severe anaemia, it was very low, leaving a vast latent iron binding capacity. The decrease of % saturation of TIBC even in normal pregnant women is indicative of inherent poor stores, which may be due to defective diet. PMID- 8449551 TI - Effect of interaction between glucose or sodium chloride ingestion and ovarian hormones on some endocrine organs in rats. AB - Adult female rats with normal oestrus cycles (control), ovariectomized (OVX), ovariectomized with estradiol treatment (OVX-EB) and ovariectomized with progesterone treatment (OVX-P), were provided with Glucose (G/W) or Saline (S/W) through a two bottle preference. They were given food pellets ad libitum. At the end of 3 weeks' period the animals were sacrificed and pituitary, thyroid, adrenal and pancreas were removed and weighed. Adrenal glands showed a significant decrease in OVX and OVX-P rats taking G/W, as also decrease in OVX and OVX-EB and increase in OVX-P rats taking S/W. The pancreas registered an overall increase in OVX, OVX-EB and OVX-P rats taking both G/W and S/W, which was statistically significant only in OVX-EB and OVX-P rats. Ovarian hormones appear to influence the size of these glands when glucose or sodium chloride is ingested. PMID- 8449552 TI - Effects of trichloroethylene anaesthesia on salivary paracetamol elimination. AB - The effect of trichloroethylene (Trielene) anaesthesia was studied in 10 young male patients undergoing short surgical procedures. Equal number of males operated upon for the same indication under epidural anaesthesia, served as a control group. Paracetamol concentrations in saliva were measured at hourly intervals on the day before and after surgery. Paracetamol half life (t1/2) significantly decreased (from 2.5 to 0.84 h) and clearance rate (CL) significantly increased (from 8.0 to 14.0 ml/min/kg) as compared to preoperative values. The control also showed significant but smaller alterations in these parameters. Our result suggests that trielene exposure may accelerate the hepatic metabolism of paracetamol. PMID- 8449553 TI - Regional metabolism of 5-hydroxytryptamine in brain under acute and chronic heat stress. AB - The metabolic alteration of 5-HT in four different regions of rat brain and plasma was studied under acute and chronic heat stress. A generalised elevation of 5-HT in all the brain regions along with high plasma level was observed in animals subjected to 4 hour heat stress at 38 degrees C. Such elevation of brain 5-HT may be due to entry of plasma 5-HT into the brain owing to breakdown of blood-brain barrier (BBB). In heat adapted rats, where BBB remained unaffected, no increase in brain 5-HT was observed, rather a significantly low level was maintained both in plasma and brain tissue. PMID- 8449554 TI - Improved colorimetric method for cholinesterase activity. AB - A modified colorimetric method for the estimation of cholinesterase activity has been worked out using two different substrates, acetylthiocholine iodide for total cholinesterase and a specific substrate, butyrylthiocholine iodide for pseudocholinesterase in the same sample. This is a modification of the method described by Voss and Sachsse (1970) wherein acetylthiocholine iodide was used for both total and pseudo cholinesterase activities. The pseudocholinesterase obtained with acetylthiocholine iodide was significantly higher (P < 0.0001) than that with butyrylthiocholine iodide either in whole blood or serum samples. Acetylthiocholine iodide while reacting with pseudocholinesterase in serum or plasma samples might also be interacting with the small quantities of acetylcholinesterase present. It is therefore suggested that butyrylthiocholine iodide and acetylthiocholine iodide may be used to determine pseudocholinesterase and total cholinesterase activities respectively. The use of two substrates with a few more alterations in the experimental conditions increased the validity of this simple and rapid colorimetric method. PMID- 8449555 TI - Effect of country liquor (Indian alcoholic beverage) on carcinogen activating and detoxifying enzymes. AB - The levels of some important drug activating and detoxyfying enzymes were estimated in the livers of Swiss mice treated with a local brand of country liquor. Following liquor ingestion in male mice elevated levels of hepatic cytochrome P-450 were observed, while female mice did not show this. Cytochrome b5 levels remained unchanged. Similarly in male mice, increase in hepatic reduced glutathione levels were obtained while in female mice, decrease in this was observed. The activity of glutathione S-transferase was not changed. It is suggested that the increases in cytochrome P-450 and in hepatic reduced glutathione may be important determinants in carcinogenecity of the country liquors. PMID- 8449556 TI - Effect of antihypertensive drugs on ethanol induced gastric lesions: is there a correlation with mucosal blood flow? AB - We studied the effect of five antihypertensive drugs on ethanol-induced gastric haemorrhagic lesions in rats. While hydralazine aggravates these lesions, nifedipine and propranolol have a protective action. On the other hand, enalapril and prazosin have no effect. Thus the effects of antihypertensive drugs on ethanol-induced lesions do not always correlate with their reported actions on gastric mucosal blood flow. PMID- 8449557 TI - Ocimum sanctum Linn--a study on gastric ulceration and gastric secretion in rats. AB - The antiulcerogenic property of Ocimum sanctum Linn (Tulsi) was studied in pyloric ligated and pyloric ligated & aspirin treated rats. The extract of OSL reduced the ulcer index, free & total acidity on acute and chronic administration. Seven days pretreatment with the drug increased the mucous secretion also. It may be concluded that OSL extract has antiulcerogenic property against experimental ulcers, and it is due to its ability to reduce acid secretion and increase mucous secretion. PMID- 8449558 TI - Serum lactate dehydrogenase in head and neck malignancy patients. AB - 50 patients of head and neck malignancy were selected for this study while excluding those associated with renal, hepatic, cardiac and metabolic diseases. Age and sex matched even number of controls were also included for comparison. Serum LDH levels in the control group were 124.2 +/- 3.50 I.U./L. Higher levels of LDH were observed in patients with malignancy of head and neck (335.50 +/- 21.60 I.U./L, P < 0.001). Serum LDH level was also related to histopathological stage of malignancy, being higher in poorly differentiated tumour as compared to moderate and well differentiated malignancy. Patients without metastasis had insignificantly lower serum LDH levels as compared to those with metastasis. PMID- 8449559 TI - Background and historical considerations of Helicobacter pylori. PMID- 8449560 TI - Diagnosis of Helicobacter pylori infection. AB - In conclusion, H. pylori infection can be detected by a variety of methods. The simplest, least expensive noninvasive method is serologic testing. Unfortunately, positive serology can only presume current infection. Urea breath testing is also noninvasive and is positive only in the setting of current infection; it is more expensive than serology and results in low-level radiation exposure when 14C urea is used. Endoscopy with biopsy is invasive and relatively expensive; however, it is readily available and is frequently performed in the evaluation of the symptomatic individual. In such cases, rapid urease testing of biopsy material is simple and less expensive than histologic examination. Histology allows simultaneous evaluation of tissue injury and infection. Frequently, routine hematoxylin-and-eosin staining is sufficient to permit identification of the bacteria; when the results of this stain are inconclusive, special stains such as Giemsa or Warthin-Starry can be used. Finally, direct culture of the organism from gastric tissue is tedious and expensive; therefore, it should generally be reserved for protocol settings or for selected patients in whom antibiotic resistant organisms are suspected. PMID- 8449561 TI - Helicobacter pylori, gastric ulcer, and agents noxious to the gastric mucosa. AB - Conclusions regarding the interaction of H. pylori infection with noxious agents such as NSAIDs, alcohol, and smoking in the development of histologic gastritis and gross gastric injury are limited by the paucity of well-performed studies specifically addressing this problem. At present, we can conclude that H. pylori prevalence is not affected by NSAIDs, alcohol, or smoking. On the other hand, reflux of duodenal contents may play a role in eradication of H. pylori after gastroenterostomy. Although NSAIDs and alcohol do cause gross gastric injury they do not appear to induce changes in the inflammatory cell infiltrate of the gastric mucosa. Rather, the histologic gastritis sometimes attributed to NSAIDs or alcohol seems to be related to the underlying presence of H. pylori. Furthermore, HP does not clearly influence the development of gross injury by NSAIDs or alcohol, and these noxious agents do not influence the H. pylori associated histologic gastritis. Patients with NSAID-associated gastric ulcers have an H. pylori prevalence similar to that of NSAID users without gastric ulcers and lower than that of patients with gastric ulcers who do not take NSAIDs. These findings suggest that NSAIDs induce ulcers through a mechanism that does not require H. pylori and histologic gastritis. Because NSAIDs are much more likely to cause gastric than duodenal ulcers, this information may explain why patients with gastric ulcers are more commonly H. pylori negative than are patients with duodenal ulcers. PMID- 8449562 TI - Helicobacter pylori infection and duodenal ulcer disease. AB - H. pylori is undoubtedly the dominant factor in the multifactorial peptic ulcer diathesis. We should not ignore the other contributing factors but rather try to identify how they interact with the organism and initiate the ulcerative process. The interplay of acid attack and mucosal defence is modulated by genetics, gender, blood group, smoking, age, and various physiologic considerations, which include acid output. These and other considerations probably explain the discrepancy between the high frequency of H. pylori infection in the population and the comparatively small proportion of individuals who develop a DU. Most agents used in DU are aimed at reducing acid secretion and achieve healing by minimizing acid attack. Such treatments, however, have no effect on H. pylori status and do not remedy the underlying gastroduodenitis. The mucosa therefore remains ill and vulnerable. After cessation of acid suppressive therapy, ulcer relapse is likely. Goodwin has likened the inflamed mucosa to a leaking roof, in which temporary dryness (healing) is assured if the rain (acid) is removed but permanent protection can be achieved only by mending the roof through healing of the mucosa. Therefore, therapy that fails to address the role of H. pylori in the causation of the mucosal inflammation, which predisposes to ulceration, is likely to confer only short-term benefit. Eradication of the infection has been shown beyond doubt to markedly alter the natural history of the disease, a number of series showing no recurrence at the end of 1 year, compared with a natural recurrence of > 70%. The economic savings after not only eradication but even suppression of H. pylori in DU disease have been estimated to be enormous. Despite these striking findings indicating H. pylori inflammation as the dominant factor in the DU diathesis and the possibilities of cure after H. pylori eradication, a large proportion of the medical community is still not willing to accept the consequences. There are presumably several reasons for this skeptical attitude. First, it takes time before physicians are willing to accept such drastic changes in their conventional way of thinking about DU disease, because it has been stressed during decades that DU disease is dominated by excessive acid as the main culprit. Second, current acid-suppressive therapy is highly efficacious in healing DU and in keeping those ulcers healed with maintenance therapy. These drugs are well tolerated and have a low side effect profile.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8449563 TI - The role of Helicobacter pylori in nonulcer dyspepsia. A debate--for. AB - Nonulcer (functional) dyspepsia is a common heterogenous disease resulting in upper gastrointestinal tract symptoms. Evidence would support that a subset of this disease is caused by H. pylori-induced gastritis. Despite the conflicting evidence, most studies evaluating H. pylori clearance and eradication, particularly the long-term studies, have observed clinical improvement in most subjects. Hill's concepts to distinguish causal from noncausal associations of an agent to a specific disease include the strength of association, consistency, specificity, temporality, biologic gradient, plausibility, coherence, experimental evidence, and analogy. There is considerable criticism of these nine aspects of epidemiologic evidence to judge whether an association is causal. These epidemiologic criteria to support that an association is causal are inappropriate when applied to H. pylori and NUD. First, the disease definition, based on clinical criteria, is imprecise, with poorly defined end points and considerable individual variability in interpretation. Second, it would appear that the cause is multifactorial, and thus, evaluation of one etiologic agent is inappropriate. In view of the potential factors to cause NUD, a scheme of treatment with a subset of eradication of H. pylori if present is advocated (Fig. 1). It is suggested that, because of the conflicting data in this area, subjects be entered into clinical trials, with eradication of H. pylori evaluated and long term follow-up of symptoms accurately monitored. PMID- 8449564 TI - The role of Helicobacter pylori in nonulcer dyspepsia. A debate--against. AB - Approximately 50% of patients with nonulcer dyspepsia harbor Helicobacter pylori gastritis, yet there is no convincing evidence that H. pylori is causally linked to chronic dyspepsia. The prevalence of H. pylori is probably not higher in patients with nonulcer dyspepsia than in the asymptomatic general population, and H. pylori is not associated with a specific symptom profile. Moreover, no plausible mechanisms to explain how histologic gastritis could induce intermittent symptoms have been identified. Finally, there is a lack of cogent experimental evidence linking H. pylori to nonulcer dyspepsia. On the basis of the available data, it must be concluded that H. pylori is unlikely to play an important role in most patients with nonulcer dyspepsia. PMID- 8449565 TI - Helicobacter pylori in the pediatric patient. AB - H. pylori is the major cause of gastritis in children and adults. Studies in children have demonstrated a specific association between H. pylori and primary gastritis. H. pylori colonization of the gastric mucosa is also important in relation to the natural history of duodenal ulcer disease. Duodenal ulcers do not appear to relapse if H. pylori is cleared from the gastric mucosa. Because of the low incidence of duodenal ulcer disease in children, a multicenter study is required to demonstrate whether this finding is true in children. To date, no specific symptoms have been associated with the presence of H. pylori gastritis in children. H. pylori gastritis may therefore be an asymptomatic condition in the majority of infected children. Further studies in relation to H. pylori gastritis and symptoms in children will be important because it should be easier to identify specific symptoms in children than in adults. H. pylori gastritis in children can be diagnosed by obtaining antral biopsy specimens for culture and histologic study during upper gastrointestinal endoscopy. Serologic study is also a sensitive and specific indicator of H. pylori infection, provided that children's sera are used to standardize the assay. Noninvasive tests such as 13C urea breath tests are very attractive for use in children but are expensive. H. pylori can be cleared from the gastric mucosa in as many as 70% of children by using a combination of metronidazole or amoxicillin with colloidal bismuth subcitrate or bismuth subsalicylate. Studies in children are important in determining the epidemiology of H. pylori. Children in Western societies are not usually colonized. Infection becomes more common with increasing age. Children in underdeveloped countries and those living in poor social conditions in Western countries are much more likely to be infected at a young age. The reason for the increased prevalence of infection among these groups is not known. There is also significant intrafamilial clustering of H. pylori infection. Again, it is unclear why the organism is clustered within households and institutions. Future studies on children will be of importance in determining whether H. pylori gastritis is a cause of specific symptoms, the epidemiology of H. pylori infection, and the possible role of the organism in the natural history of gastric cancer. PMID- 8449566 TI - Treatment strategies for Helicobacter pylori infection. AB - Helicobacter pylori can be eradicated easily in most patients with a 14-day triple-therapy regimen. In patients in whom this treatment fails or who cannot take a full course, other antimicrobial combinations must be considered. This article discusses the various alternatives and explains why various agents should or should not be used. It also includes many new therapies developed in 1992 that allow the physician to treat virtually all H. pylori infections. PMID- 8449567 TI - Common-sense management of Helicobacter pylori-associated gastroduodenal disease. Personal views. AB - We have tried to present a rational approach to the medical treatment of peptic ulcer disease and nonulcer dyspepsia in the era of H. pylori. We are aware that the natural history of peptic ulcer disease is still debated. Some clinicians believe that peptic ulcer disease may "burn out" over a 10- to 15-year period, and in light of this, the emphasis toward a nonsurgical "cure" for peptic ulcer disease may seem misguided. Yet, all factors must be taken into account. Current medical therapy has demonstrated inadequacies. H. pylori is unequivocally (in our view) associated with peptic ulcer disease. Anti-H. pylori therapy has proven efficacy in the long-term prevention of peptic ulcer recurrence. Despite our enthusiasm for treatment of H. pylori in select circumstances, we encourage further controlled clinical trials to better delineate the role of H. pylori in the natural history and treatment of peptic ulcers. The association between H. pylori and nonulcer dyspepsia is tenuous at best. Treatment directed at eradicating H. pylori in nonulcer dyspepsia does not impress us favorably. We are intrigued by preliminary data that, despite a lack of improvement in the short term, H. pylori eradication in nonulcer dyspepsia patients may reduce symptoms over the long term. Unfortunately, this study suffers methodologic difficulties. If other studies were to confirm these findings, this would provide a cogent reason for us to reassess our views on the treatment of H. pylori in nonulcer dyspepsia. At present, the costs, benefits, and risks of anti-H. pylori therapy in nonulcer dyspepsia are not sufficient to warrant its use outside of therapeutic trials. PMID- 8449568 TI - Gastric bacteria other than Helicobacter pylori. AB - Since the culture of Helicobacter pylori from the human stomach in 1983 there has been renewed interest in other bacteria that had been observed in animal stomachs as early as late in the nineteenth century. Many of these bacteria have now been isolated and have been shown to belong to the same genus, Helicobacter, which currently contains nine species. Study of the gastric helicobacters is important because it provides relevant information about how bacteria can survive in the gastric environment and induce disease. Bacteria of special importance include "Gastrospirillum hominis," a distinctive tightly spiralled bacterium commonly found in cats and dogs, recently shown to be a helicobacter, and that infects a small proportion of human patients, causing a mild chronic gastritis; Helicobacter felis, a bacterium isolated from cats that has been found to be associated with gastritis in one human patient but easily colonizes small laboratory animals, causing gastritis and thus providing a useful model of the human infection; and Helicobacter mustelae, the natural inhabitant of the ferret gastric mucosa, where it also induces a form of chronic gastritis. The latter bacterium shares important properties with H. pylori, namely an ability to adhere firmly to gastric mucosae and an association with peptic ulceration. Investigation of these non-H. pylori gastric bacteria in natural or experimental hosts provides useful models of H. pylori-associated gastroduodenal disease, makes possible assessment of potential therapeutic regimens, and provides information that may result in the development of novel intervention strategies. PMID- 8449569 TI - Pathogenic mechanisms of Helicobacter pylori. AB - There is general agreement that motility, urease activity, and association with gastric mucosal cells are important virulence factors of H. pylori. Urease activity is perhaps the best characterized of these factors. Presumably, urease activity creates a "cloud" of ammonia around the bacterium, thus neutralizing the lethal effects of gastric acid. Motility allows the bacterium to penetrate the mucus layer and promotes specific association of the bacteria with epithelial cells, further allowing evasion of gastric acidity. The association between gastrin levels and H. pylori infection is currently the most thoroughly studied feature relating to pathogenesis in vivo. Prolonged hypergastrinemia associated with H. pylori infection may contribute to increased parietal cell mass and chronically increased secretion of gastric acid; however, long-term studies are needed to validate this hypothesis. The identification of mucosal gamma delta T cells and immunologic cross-reactivity between H. pylori and gastric cells implies that the immune response contributes significantly to the pathogenesis of H. pylori. The role of the immune system in modulating H. pylori infection requires further study. Although many putative pathogenic factors have been identified on the basis of in vitro phenomena alone, their significance in vivo is not known. Ultimately, it will be necessary to evaluate the significance of these factors in animal models by using isogenic strains of H. pylori that differ only in a single genotypic characteristic. PMID- 8449570 TI - Microbiology of Helicobacter pylori. AB - The new genus name Helicobacter was first published in October 1989. H. pylori is a unipolar, multiflagellate, gently spiral organism found on the human gastric mucosa, but in culture and under unfavorable conditions, coccoidal forms emerge, which may be indicative of a dormant state. The biology and metabolism of H. pylori, together with growth requirements and methods of detection in clinical specimens, are described in this article. Enzymes, hemagglutinins, and antibiotic susceptibilities of H. pylori are delineated. PMID- 8449571 TI - Helicobacter pylori-associated gastric pathology. AB - H. pylori is the most common cause of nonerosive nonspecific gastritis; however, its main importance has been as a marker in research studies of eradication in relation to duodenal ulcer relapse. In developed countries, the most common histologic pattern appears to be that of a mild superficial chronic active gastritis. When H. pylori is present in the antrum it is virtually always present in the body as well, although inflammation in body mucosa is usually milder than that in the antrum. The organisms do not overlie areas of intestinal metaplasia; thus, H. pylori is commonly absent in individuals with diffuse intestinal metaplasia as seen in severe atrophic gastritis. Studies of H. pylori gastritis have been of enormous value in research studies; however, in the clinical management of the individual patient there is only limited value to documenting the presence, character, and severity of H. pylori gastritis. PMID- 8449572 TI - Epidemiology of Helicobacter pylori infection. AB - Recent studies have shown that seroprevalence curves of Helicobacter pylori infection in fact reflected the rate of acquisition in childhood. Although the reservoir is well known, the routes of infection are still poorly understood: Are they oral-oral or fecal-oral? PMID- 8449573 TI - Helicobacter pylori and gastric cancer. AB - Gastric cancer remains among the leading types of cancer worldwide. There is now convincing evidence linking H. pylori to adenocarcinomas of the gastric antrum, body, and fundus. These tumors are rapidly decreasing in incidence in the United States, whereas cardia tumors, tumors unassociated with H. pylori infection, are on the increase. Although criteria for causality have not been completely fulfilled for H. pylori and adenocarcinoma, there are plausible mechanisms by which chronic inflammation could induce carcinogenesis ("mitosis causes mutagenesis"). Because gastric cancer is unusual in the United States, screening and treatment of H. pylori in the general population are unwarranted. Chemoprevention in high-risk populations, however, could potentially be used to decrease risk for adenocarcinomas distal to the cardia. PMID- 8449574 TI - Vaccination of adults against travel-related infectious diseases, and new developments in vaccines. AB - The number of people travelling to tropical or subtropical countries, whether for holidays or for business, is steadily increasing. Many of these travellers are at risk of acquiring an infectious disease. Protection against certain infectious diseases is possible by vaccination. Vaccinations required or recommended for adults are reviewed here. Progress in the refinement of available vaccines, as well as the development of new vaccines, is discussed. PMID- 8449575 TI - Spread of Klebsiella pneumoniae producing SHV-5 beta-lactamase among hospitalized patients. AB - The first outbreak of infections caused by an SHV-5 producing strain of Klebsiella pneumoniae is reported. Within a period of 1 year and 9 months, multiresistant K. pneumoniae strains caused severe infections, mostly of the lower respiratory tract, in 22 patients. The strains were resistant to penicillins, third-generation cephalosporins, aztreonam, chloramphenicol, tetracycline and co-trimoxazole. The resistance determinants were transferable to Escherichia coli. All isolates produced a beta-lactamase with a pI of 8.2. Ceftazidime was hydrolyzed at this band. These characteristics, together with the resistance phenotype, are identical to those of a reference strain producing the beta-lactamase SHV-5. The K. pneumoniae strains of all patients were identical in their capsular serotype (K1), plasmid pattern and plasmid fingerprint after digestion with Dra I restriction endonuclease. We conclude that this outbreak was caused by the spread of one clone of K. pneumoniae producing SHV-5 beta-lactamase among patients of different wards. Our results indicate a real risk for failure of therapy by third-generation cephalosporins in intensive care patients due to SHV-5 producing pathogens. PMID- 8449576 TI - Haematological manifestations of childhood brucellosis. AB - Very few data on the frequency and diversity of haematological abnormalities occurring in brucellosis in children have been reported. In the present study 110 children (56 boys and 54 girls; age range, 2 months to 14 years) with proven brucellosis were investigated to determine the haematological changes during the active course of this infection. Anaemia was detected in 48 (44%) patients, of whom four had evidence of haemolysis. Leukopenia occurred in 33% of the cases, with neutropenia and/or lymphopenia being the most striking features encountered. Thrombocytopenia was found in six (5%) patients and pancytopenia in 15 (14%) patients, of whom one developed disseminated intravascular coagulation. Clinically detectable bleeding occurred in five (4.5%) patients whose platelet counts were significantly low. Hypersplenism, haemophagocytosis and granulomatous lesions of the bone marrow appear to play a fundamental role in producing these abnormalities of the peripheral blood. Brucellosis may be considered in patients whose blood picture reveals haemolytic anaemia, leukopenia, thrombocytopenia or pancytopenia, particularly when the disease is epidemiologically suspected. PMID- 8449577 TI - Toxocara antibodies in patients with visceral or ocular disorder in Slovenia. AB - The incidence of Toxocara antibodies was determined in 319 sera from patients suspected of having Toxocara infection. Serological responses were compared with clinical manifestations and age of the patients. A seropositive reaction was found in 24% of the patients. Highly positive results (OD 0.510-1.000 and OD > 1.000) by ELISA were obtained significantly more frequently in younger patients than in older ones (p < 0.005). The percentage of seropositive patients with visceral disorder was found to decrease with age, whereas the proportion of seropositive patients with ocular disorder increased with age. Serologically confirmed Toxocara infection in Slovenia alerted us to the fact that this health issue should be given due attention in the future. PMID- 8449578 TI - Absorption of pivampicillin as related to dose, and tolerability of a 700 mg tablet. AB - To evaluate the absorption and tolerability of a new formulation of pivampicillin administered as a 700 mg tablet, 14 healthy volunteers received single doses of 350, 500 and 700 mg p.o. Maximum serum concentrations (Cmax) of 5.73, 7.05 and 8.61 mg/l were obtained. The corresponding values for the area under the concentration/time curve (AUC) were 12.32, 18.99 and 25.30 mg/lxh. Concomitant intake of food increased the Cmax of the 700 mg tablet to 9.5 mg/l, while the AUC remained unchanged. Co-administration of the 700 mg pivampicillin dose with an antacid reduced the Cmax to 7.45 mg/l and the AUC to 17.92 mg/l x h. The tolerance of the 700 mg tablet was evaluated in a double-blind placebo-controlled study involving 57 patients. Six percent of the patients in each treatment group reported minor adverse reactions. PMID- 8449579 TI - Cefuroxime axetil versus ofloxacin for short-term therapy of acute uncomplicated lower urinary tract infections in women. AB - In a multicentre study 163 women with acute lower urinary tract infection were treated orally with either 125 mg cefuroxime axetil or 100 mg ofloxacin twice daily for three days. Both antimicrobial agents were generally well tolerated. Four patients in the group treated with cefuroxime axetil and two in the group treated with ofloxacin experienced adverse events. Clinical cure and improvement were registered in 56 of 66 (84.8%) and 59 of 62 (95.2%) of the evaluable patients treated with cefuroxime axetil and ofloxacin, respectively. Seven to nine days after therapy, bacteriuria (CFU < 10(3)/ml) had been eliminated in 53 of 66 (80.3%) and 57 of 64 (89.1%) of the evaluable patients receiving cefuroxime axetil and ofloxacin, respectively. The results were not statistically significantly different (p > 0.1). Pathogens present at baseline were eliminated by up to an MIC of 16 mg/l of cefuroxime axetil, independent of susceptibility to this agent. There was no difference with regard to efficacy and tolerance between patients treated with cefuroxime axetil and those treated with ofloxacin. On the basis of the MICs of six antimicrobial agents (cefuroxime, ofloxacin, cefadroxil, ampicillin, trimethoprim with and without sulfamethoxazole) determined for the pathogens isolated prior to therapy, resistance rates were lowest for cefuroxime (2.2%) and ofloxacin (3.4%). PMID- 8449580 TI - HIV transmission by needle stick and eczematous lesion--three cases from Germany. AB - Two cases of documented HIV-1 transmission by needle stick and one case of probable transmission by eczematous lesion in three nurses in Germany are reported in the period 1988 to 1991. In two of the cases the nurse knew of the AIDS status of the index patient. A review of the three cases reiterates the importance of repeated training on the prevention of accident and on measures to be taken after an accident, as well as the need to keep the workplace free of additional burden when AIDS or HIV-infected patients are treated. PMID- 8449581 TI - Prevention of hepatitis B virus (HBV) infection in health-care workers after accidental exposure: a comparison of two prophylactic schedules. AB - The efficacy of hepatitis B (HB) vaccine alone or combined with hepatitis B immunoglobulin (HBIg) in preventing hepatitis B virus (HBV) infection was studied in a controlled trial. Recombinant HB vaccine (Engerix-B, 20 micrograms) was given to 40 susceptible health-care workers within three days of exposure (Group B). In another group of 37 medical professionals a single dose of HBIg (0.06 mg/kg) was administered intramuscularly within three days of exposure, followed immediately by the first dose of vaccine (20 micrograms dose) (Group A). In both groups the next doses of recombinant vaccine were administered one, two and six months later. One month after the fourth dose of vaccine the percentage of incidence of antibody to hepatitis B virus surface antigen (anti-HBs) was 94.6% in group A and 95% in group B with geometric mean titer of antibodies of 340 and 380 mIU/ml, respectively. A control group consisted of 34 persons who did not receive any specific immunoprophylaxis (Group C). All subjects were followed for at least ten months. The protective value of immunization, both active alone and combined passive and active, was clearly effective since none of the recipients developed acute symptomatic HBV infection compared with two (6%) of 34 not immunized persons (Fisher's exact test p = 0.01). Thus, in the absence of evidence of lesser efficacy for the use of HB vaccine alone after exposure to HBsAg-positive blood, this schedule would seem to be the treatment of choice in adult persons. PMID- 8449582 TI - Polyphasic type A hepatitis: histological features. AB - The histology of polyphasic type A hepatitis was analyzed in liver biopsy specimens of two patients. The microscopic examination showed, together with changes of acute viral hepatitis, portal plasma cell infiltration, limiting plate erosion and porto-portal bridging necrosis. These features, although sometimes described in classical HAV hepatitis, appear to be similar to those commonly observed in severe and evolving forms of acute hepatitis due to other hepatotropic viruses. Only careful serological analyses can lead to a correct diagnosis and prognosis in case of polyphasic type A hepatitis. PMID- 8449583 TI - Timing, dosing and duration of antimicrobial prophylaxis in urology: a study in guinea pigs with special reference to high-risk conditions. AB - A study in guinea pigs was performed to investigate the importance of timing, dosage and duration of antimicrobial prophylaxis in urologic surgery. To simulate high-risk conditions, in one group a foreign body was implanted subcutaneously. The prostate and one kidney were cauterized and bacteremia was induced by intravenous injection of an Escherichia coli suspension. Various ciprofloxacin regimens were tested. The results indicate that antimicrobial prophylaxis is beneficial only if administered before or shortly after surgery. Full therapeutic dosage may not be necessary for prophylactic efficacy. Single-dose prophylaxis was as effective as multiple doses. Foreign body infection could be prevented by single-dose prophylaxis. PMID- 8449584 TI - Clostridium perfringens septicemia with massive hemolysis. AB - Massive hemolysis and renal failure are rare complications of infection with Clostridium perfringens, resulting in a very high mortality rate (70-100%). The severity of the infection depends on the presence of underlying conditions such as malignancies and diabetes mellitus. In patients without underlying disorders, massive hemolysis and anuria have been observed in only eight cases, according to recent reports. This case report describes a 61-year-old man who died of C. perfringens septicemia with massive hemolysis and anuria less than 4 h after admittance to the hospital, despite rapid and adequate antibiotic treatment. No focal infection was found. PMID- 8449585 TI - Meningitis due to Fusobacterium necrophorum subspecies necrophorum. Case report and review of the literature. AB - This paper reports a case of fatal meningitis caused by Fusobacterium necrophorum subsp. necrophorum in a previously healthy five-year-old child. The organism was isolated in pure culture from the cerebrospinal fluid and from intracranial pus obtained at autopsy. The role of F. necrophorum in the development of meningitis is reaffirmed and its isolation and identification are discussed. The clinical presentation of the present case resembles the previously published reports and highlights the poor prognosis in spite of appropriate antibiotic treatment. PMID- 8449586 TI - Tissue and serum concentrations of ofloxacin in the ear region following a single daily oral dose of 400 mg. AB - Even after a single daily dose of 400 mg, the concentrations of ofloxacin in infected middle ear tissues are within the therapeutic range. Even 20 h after a single dose of 400 mg ofloxacin, the tissue concentrations in cartilage and cholesteatomatous matrix are in excess of the minimal inhibitory concentration for a number of pathogens, such as Staphylococcus aureus and Haemophilus influenzae. The especially high concentrations in middle ear mucosa, auricular cartilage and cholesteatomatous matrix are striking. No complications or side effects were observed during ofloxacin treatment in this study. The study demonstrates that a dose of 400 mg ofloxacin per day is an effective and patient orientated therapeutic regime for the treatment of ENT infections, particularly of ear infections. PMID- 8449587 TI - Penetration of ofloxacin into nasal tissues. AB - The average concentration in 75 female/male patients was 1.90 +/- 1.10/1.55 +/- 0.62 mg/l in serum, 0.81 +/- 0.42/0.74 +/- 0.48 mg/kg in bone, 2.40 +/- 1.16/1.94 +/- 0.87 mg/kg in cartilage, and 2.35 +/- 1.28/1.99 +/- 1.02 mg/kg in mucosa. In each case the highest serum or tissue concentrations were observed 2 hours after the last ofloxacin administration (serum 2.60 +/- 0.41 mg/l, bone 1.10 +/- 0.75 mg/kg, cartilage 3.40 +/- 0.86 mg/kg, mucosa 3.50 +/- 1.05 mg/kg), but even 8 hours after the last dose the levels still exceeded the MIC 90% of e.g. Pseudomonas aeruginosa, Staphylococcus aureus or Haemophilus influenzae. The clinical investigations carried out show that ofloxacin represents a new oral therapeutic agent of significant value in otorhinolaryngology, particularly in the treatment of problematic infections. As the investigations show, the level in healthy tissue is definitely within the therapeutic region for a period of 8 hours. In ENT (nasal and paranasal) infections, ofloxacin should be given for defined indications, e.g. for oral therapy of problematic infections due to P. aeruginosa, and if possible after identification of the pathogen. PMID- 8449589 TI - A four compartment open model with first-order absorption. AB - This paper is related to the identification of pharmacokinetic parameters of a four-compartment open model with first order absorption from plasma level data. The eigenvalues of the characteristic matrix of the given system are obtained by transforming them into a single variable and the solution involves the minimization of the sum of squares of deviation of the model-predicted values of the state variables from an experimentally obtained values. The distribution volume and the lag time are also identified. Finally, the unicity of the absorption rate constant is obtained by the minimum energy principle. The results obtained with present method are compared with those obtained by the generalized least squares method. PMID- 8449588 TI - Efficacy and pharmacokinetics of teicoplanin in hemodialysis patients. AB - In order to establish guidelines for the dosage of teicoplanin, a new glycopeptide antibiotic, in patients with end stage renal failure, 40 cases of suspected or proven gram-positive infections were treated with teicoplanin. Three different dosage regimens were used and peak/trough serum levels measured. Thirty one patients were cured and six patients died. Teicoplanin was well tolerated. For severe cases of septicemia with staphylococci in patients undergoing hemodialysis a teicoplanin therapy consisting of 800 mg on day 1 followed by administrations of 400 mg on days 2, 3, 5, 12, and 19 is recommended. Minor infections are treated initially with 800 mg followed by administration of 400 mg at weekly intervals. PMID- 8449590 TI - Regression imputation of missing values in longitudinal data sets. AB - A stand-alone, menu-driven PC program, written in GAUSS, which can be used to estimate missing observations in longitudinal data sets is described and male available to interested readers. The program is limited to the situation in which we have complete data on N cases at each of the planned times of measurement t1, t2,..., tT; and we wish to use this information, together with the non-missing values for n additional cases, to estimate the missing values for those cases. The augmented data matrix may be saved in an ASCII file and subsequently imported into programs requiring complete data. The use of the program is illustrated. Ten percent of the observations in a data set consisting of mandibular ramus height measurements for N = 12 young male rhesus monkeys measured at T = 5 time points are randomly discarded. The augmented data matrix is used to determine the lowest degree polynomial adequate to fit the average growth curve (AGC); the regression coefficients are estimated and confidence intervals for them are determined; and confidence bands for the AGC are constructed. The results are compared with those obtained when the original complete data set is used. PMID- 8449591 TI - Flow of an elastico-viscous liquid in a curved pipe of slowly varying curvature. AB - Curvature forms an important feature of thoracic aorta and this paper deals with the flow of an idealized elastico-viscous liquid in a curved pipe of circular cross-section and slowly varying curvature, under a pressure gradient. The flow is assumed to be steady and at low Reynolds numbers. By using the series expansion method of Dean (Phil Mag 4 (1927) 208-223; Phil Mag 5 (1928) 673-693) in powers of a parameter L, which can be considered as the square of ratio of the centrifugal force induced by the circular motion of the fluid to the viscous force, it is shown that in a tube of increasing curvature, there will be delay in setting up of the secondary motion. The wall shear stress, an important parameter in physiological flows, is calculated. The flow of Newtonian fluid in a tube of circular cross section is discussed, as a particular case. PMID- 8449592 TI - Osmosis: a microcomputer laboratory teacher. AB - A computer simulation of osmotic processes has been developed. Several experimental setups are graphically simulated and may be freely selected by the user. The simulation analyzes the basic factors which determine the osmotic pressure and volume flow of a solution (e.g. concentration, temperature, activity coefficient, Staverman's coefficient and external pressure). The program was written in Turbo Pascal to operate in IBM-PCs or compatibles. High quality graphical display of results maintains the students' interest. A user's guide and continuous help for the available options simplify its use. Computer simulation seems to be a very well suited aid for teaching osmotic phenomena, improving both theoretical knowledge and the ability of the students to empirically demonstrate some of the basic laws of osmotic phenomena. PMID- 8449593 TI - Models for computer simulation studies of input functions for tracer kinetic modeling with positron emission tomography. AB - In tracer kinetic modeling with Positron Emission Tomography (PET), the direct measurement (piecewise linear approximation) of plasma time-activity curve of tracer (PTAC) is often used as the input function to estimate regional physiological parameters. However, no explicit general model is available for PTAC itself, which limits the further study of the effects of PTAC, such as PTAC measurement noise or PTAC sampling schedules, on the physiological parameters estimation. A PTAC model is proposed in this paper and compared with other four possible candidates. Eight sets of [18F]-fluoro-2-deoxy-D-glucose (FDG) experimental data were used to test the models and several statistical criteria were used to validate their adequacy. An application of the model to improve the estimation of local cerebral metabolic rate of glucose (LCMRGlc) is presented. This model is also expected to be useful for generating realistic PTAC curves in computer simulation studies of other tracers and their kinetic modeling characteristics. PMID- 8449594 TI - Food-group consumption and colon cancer in the Adelaide Case-Control Study. I. Vegetables and fruit. AB - Previous epidemiologic studies have shown an inverse association between vegetable and fruit consumption and risk of colon cancer. Vegetables and fruit contain a large number of potentially anti-carcinogenic substances, thus lending biological plausibility to this association. We conducted a case-control study in Australia, comparing 220 persons with histologically confirmed incident adenocarcinoma of the colon with 438 age- and gender-matched controls. Cases were identified via the South Australian Cancer Registry (1979-80); controls were randomly selected from the electoral roll. All participants completed a 141-item food-frequency questionnaire and were interviewed regarding demographic and other information. Consumption of 15 vegetable and fruit groups was investigated. Odds ratios (OR) for quartiles of consumption were derived using conditional logistic regression. All analyses were conducted separately for females and males. For females, greater intakes of onions and legumes were associated with decreased risk, with protein-adjusted OR of 0.48 and 0.53 respectively. Greater intakes of raw fruit and cabbage were associated with protein-adjusted OR of 0.76 and 0.71 respectively. For males, greater intakes of onions, green leafy vegetables, legumes, carrots and cabbage were associated with protein-adjusted OR in the range of 0.72 to 0.77. Consumption of potatoes was positively associated with risk in both genders. All 95% confidence intervals included 1.0. Analyses stratified by colon-cancer sub-site showed no strong and consistent differences between sub-sites for the vegetable and fruit associations. Results for meat, poultry, seafood, dairy foods and eggs are presented in a companion report. PMID- 8449595 TI - Food-group consumption and colon cancer in the Adelaide Case-Control Study. II. Meat, poultry, seafood, dairy foods and eggs. AB - We conducted a case-control study in Australia, comparing 220 persons with histologically confirmed incident adenocarcinoma of the colon with 438 age- and gender-matched controls. Cases were identified via the South Australian Cancer Registry (1979-80); controls were randomly selected from the electoral roll. All participants completed a 141-item food-frequency questionnaire and were interviewed regarding demographic and other information. Consumption of 8 groups of foods from animal sources was investigated. Odds ratios (OR) for quartiles of consumption were obtained using conditional logistic regression. All analyses were conducted separately for females and males. The most striking finding was a positive association for egg consumption in females, with an unadjusted OR of 2.4 (1.1-5.3) for consumption in the uppermost quartile. The uppermost septile of egg consumption was associated with an unadjusted OR of 6.3 (1.5-26.1) and a dose response pattern was suggested. Intakes of red meat, liver, seafood, and dairy foods were also weakly positively associated with risk in females. In males, intakes of red meat and poultry were weakly positively associated with risk with unadjusted ORs of 1.5 (0.8-2.8) and 1.4 (0.7-2.6) respectively. The ratio of intake of red meat to poultry and seafood was also positively associated with risk in males, with an unadjusted OR of 1.4 (0.8-2.6). Interpretation of analyses stratified by colon cancer subsite was limited by the low number of subjects in each sub-site stratum, yet the results were somewhat supportive of a stronger risk associated with animal foods in the proximal than in the distal colon. The results for egg consumption suggest a role for cholesterol in the etiology of colon cancer, particularly in proximal cancer for females. Results for vegetable and fruit consumption are presented in a companion report. PMID- 8449596 TI - Cholecystectomy and colorectal cancer: evidence from a cohort study on diet and cancer. AB - The association between cholecystectomy and subsequent risk for colorectal carcinoma was investigated in a prospective cohort study on diet and cancer (n = 120,852), which is being conducted in the Netherlands from 1986 onwards among 120,852 men and women, aged 55 to 69. After a follow-up period of 3.3 years, 478 incident cases of colorectal cancer (258 men and 220 women) were identified in the cohort, 64 of whom reported at baseline to have undergone previous gall bladder surgery (21 men and 43 women). After adjustment for age and familial history of large-bowel cancer, the relative rate (RR) for colorectal cancer in subjects who had undergone cholecystectomy compared with those who had not was 1.81 in men (p = 0.02) and 1.47 in women (p = 0.05). Additional adjustment for parity. Quetelet index, alcohol intake and other dietary variables resulted in a RR of 1.78 in men and 1.51 in women. In women, the highest RR was detected in the right colon (RR = 1.89), whereas in men, no site within the large bowel accounted specifically for the increased relative rate. In both men and women, the rate appeared to increase from approximately 6 years after cholecystectomy onward. According to the TNM stage of the disease, cholecystectomized patients were not detected at an earlier stage than the other patients. It is concluded that in this study the positive association between colorectal cancer and cholecystectomy cannot be explained by detection bias or ascertainment bias and is not confounded by risk factors for gallstone disease or dietary factors. PMID- 8449597 TI - Cancer risk in farmers: results from a multi-site case-control study in north eastern Italy. AB - The relationship between farming and cancer risk was investigated in an integrated series of case-control studies conducted from 1985 to 1991 in the Friuli Venezia Giulia region, north-east Italy. Patients with cancer of the oral cavity and pharynx, larynx, oesophagus, colon and rectum, pancreas, breast, thyroid gland, kidney and urinary tract, bladder, prostate, soft-tissue sarcomas, Hodgkin's diseases, non-Hodgkin's lymphomas and multiple myelomas, and controls admitted to hospital for acute, non-neoplastic conditions, were interviewed. For males, a significantly elevated relative risk was seen for oral cavity and pharynx. Farming, however, was associated with a significant protection against cancer of the colon and rectum and bladder. In females, only one significant association emerged, for multiple myeloma. A few significant interactions between cancer risk and year of birth (i.e., before 1930 or 1930 and after) were observed. The risk of cancer of the larynx was significantly elevated in younger male farmers but not in older ones. Our multi-site case-control study confirms that farmers have, for some cancer sites, a distinctive pattern. Excesses of cancer of the oral cavity and pharynx in farmers are characteristic of the present study area and, possibly, of similar European rural populations who have in common high levels of alcohol consumption and, at least in the past, unbalanced diets. PMID- 8449598 TI - Effect of monoclonal antibody 17-1A and GM-CSF in patients with advanced colorectal carcinoma--long-lasting, complete remissions can be induced. AB - Antibody-dependent cellular cytotoxicity (ADCC) is considered to be one of the effector functions of unconjugated monoclonal antibodies (MAbs) in tumor therapy. The antitumor activity of MAbs might therefore be augmented if the cytotoxic capability of the effector cells could be increased. In an in vitro system, the killing capacity of MAb was significantly enhanced by pre-treatment of the effector cells with granulocyte-macrophage colony-stimulating factor (GM-CSF). Based on these findings, the therapeutic effect of the combination of mouse MAb 17-1A (IgG2a) and GM-CSF was evaluated in 20 patients with metastatic colorectal carcinoma (CRC). The patients received GM-CSF for 10 days and a single i.v. infusion of MAb 17-1A on day 3 of the cycle. Four cycles were given at 1-monthly intervals. There was a continuous increase in blood monocytes and lymphocytes during all 4 GM-CSF cycles. Neutrophils and eosinophils were also significantly augmented but in a biphasic manner and the cell counts on day 10 of cycle IV were significantly lower than in cycles I and II. GM-CSF-related side-effects were of no major clinical importance. During the third cycle, an immediate-type allergic reaction (ITAR) against MAb 17-1A occurred in most patients, necessitating reduction of the MAb dose as well as of the infusion rate. Two patients achieved complete remission. One patient had a minor response, and 3 other patients were considered to have stable disease > 3 months. PMID- 8449599 TI - CA 494--a new tumor marker for the diagnosis of pancreatic cancer. AB - In 59 patients with ductal pancreatic cancer the monoclonal antibody (MAb) BW 494, which detects the CA 494 glycoprotein antigen, was analyzed in comparison with the reference tumor markers CA 19-9 and CEA. Eighty-one patients with non pancreatic malignancies of the gastrointestinal (GI) tract, 95 with chronic pancreatitis, 124 with benign non-pancreatic GI diseases, 30 with diabetes mellitus (type I or type II) and 114 healthy blood donors served as controls. The sensitivity of pancreatic cancer was 90%, 44% and 90% for CA 19-9, CEA and CA 494, respectively. In chronic pancreatitis, as the most important control population for pancreatic cancer, the specificity was 85%, 72% and 94% for CA 19 9, CEA and CA 494, respectively. PMID- 8449600 TI - Cancer incidence trends in urban Shanghai, 1972-1989. AB - Incidence data pertaining to more than 250,000 cancer cases diagnosed during the years 1972-1989 among residents of urban Shanghai, China, were analyzed to determine the relative importance of the various malignancies and to discover changes over time. In the most recent 3-year period, lung cancer was the most frequent cancer among men (57.0 per 100,000 person-years, age-adjusted world standard), followed by cancers of the stomach (50.1), liver (29.6), esophagus (13.3), colon (11.2) and rectum (9.4). Among women, breast cancer leads (25.1), followed by cancers of the stomach (23.2), lung (18.8), liver (10.9), colon (10.2) and rectum (7.3). The most impressive increases in incidence rates from 1972-74 to 1987-89 were observed for cancers of the gallbladder (119% and 101% among men and women, respectively), colon (85% and 78%), and brain and other nervous system (71% and 60%). In addition, increases of 20-50% occurred for cancers of the pancreas, male lung, female breast, corpus uteri, kidney, and for non-Hodgkin's lymphoma. Rates declined notably for cancers of the esophagus (-54% and -53%), cervix uteri (-86%), and to a lesser extent (10-20%) cancers of the male stomach and liver. These observed trends can be explained only partly by improvements in cancer diagnosis and completeness of the cancer registry, and most likely reflect changes in the prevalence of risk factors in this population. PMID- 8449601 TI - Orthodox Jews have a lower incidence of malignant melanoma. A note on the potentially protective role of traditional clothing. AB - The incidence of malignant melanoma (MM) in orthodox and non-orthodox Jews in Israel during the years 1970-1982 was compared through an assessment of incidence rates in the orthodox and non-orthodox neighborhoods in the city of Jerusalem and by a comparison of the rates in 2 cities on the outskirts of Tel Aviv, one of which has a strongly orthodox population. Within the city of Jerusalem the incidence of MM for the European-American born in the orthodox neighborhoods was significantly lower than in the rest of the city in males, and of borderline significance in females. A similar pattern was seen upon comparison of the orthodox city of Bnei Brak to its neighbor city, Givatayim. The findings are consistent with the role of sun exposure in the etiology of malignant melanoma. PMID- 8449602 TI - int-2 amplification in breast cancer: association with decreased survival and relationship to amplification of c-erbB-2 and c-myc. AB - Amplification of the int-2 oncogene was measured in a series of breast tumours and related to amplification of the c-myc and c-erbB-2 oncogenes, histopathological features and relapse-free and overall survival. int-2 was amplified in 11%, c-myc in 20% and c-erbB-2 in 27% of the tumours assessed. int-2 amplification was associated with large tumour size (p < 0.05) and reduced relapse-free (p < 0.05) and overall (p < 0.0005) survival. c-myc amplification was associated with poor tumour differentiation (p < 0.05) but had no association with prognosis. c-erbB-2 amplification was associated with low levels of expression of oestrogen receptor mRNA (p < 0.05), poor tumour differentiation (p < 0.05) and shortened relapse-free (p < 0.0001) and overall survival (p < 0.0001). This is the first report of an association between amplification of the int-2 oncogene in breast tumours and a significantly increased risk of death from breast cancer, and suggests that int-2 may be useful for identifying breast cancer patients having a poor prognosis. PMID- 8449603 TI - Loss of RB protein expression in primary bladder cancer correlates with loss of heterozygosity at the RB locus and tumor progression. AB - RB-protein status as determined by immunohistochemical analysis was compared with loss of heterozygosity (LOH) at the RB locus in 68 primary transitional-cell carcinomas of the bladder. Absence of RB-protein expression was found in 15 of 17 tumors in which LOH at the RB locus was identified, whereas 31 of 36 tumors from informative patients which showed no LOH had a normal RB-protein pattern (p < 0.001). Altered RB-protein expression was also more frequently seen in muscle invasive and high-grade tumors (p < 0.003 and < 0.005, respectively). Our results indicate that LOH at the RB locus is highly correlated with loss of RB-protein expression in primary bladder carcinomas and further strengthens the notion that loss of RB function may be associated with more aggressive bladder tumors. PMID- 8449604 TI - Relation between autoradiographically measured blood flow and ATP concentrations obtained from imaging bioluminescence in tumors following hyperthermia. AB - The effects of moderate local hyperthermia (43.3 degrees C/30 min) on regional blood flow and regional ATP distribution in the amelanotic hamster melanoma A-Mel 3 were investigated by high-resolution techniques. Blood flow and ATP concentrations were measured simultaneously in treated and untreated tumors and in adjacent tissues by means of (14C)-Iodoantipyrine autoradiography and quantitative imaging bioluminescence in consecutive tissue sections at 3, 12 and 24 hr following treatment. Digital image processing and the use of a special algorithm allowed the regional interrelationship of the 2 parameters to be quantified. Measurements revealed a great heterogeneity of blood flow and ATP between and within the tumors. A pronounced reduction of blood flow and ATP in tumors was observed after hyperthermia in comparison to untreated controls. The adjacent tissue remained mostly unaffected. However, a weakly positive relationship between the 2 parameters was obtained when variables were averaged in tumors or groups. At the microregional level, the untreated tumor tissue revealed a significant, positive correlation between nutritional blood flow and ATP concentrations. This local correlation was reduced and changed with time after treatment indicating different time courses of the parameters. Hyperthermia induced a sudden decrease in blood flow, later associated with a decline in ATP. A slight recovery of both parameters was observed 24 hr after hyperthermia. The results indicate that the metabolic status of the tumor cells is critically dependent on nutritional blood flow but also on the energy requirement of the individual tumor. PMID- 8449605 TI - Effects of all-trans retinoic acid as a potential chemopreventive agent on the formation of azoxymethane-induced aberrant crypt foci: differential expression of c-myc and c-fos MRNA and protein. AB - The main objectives were to determine the modulating effects of all-trans retinoic acid on the number, size and multiplicity of aberrant crypt foci as well as the in vivo expression of the genes c-myc and c-fos. These foci, which are hypothesized to be the pre-malignant lesions of colon cancer, were induced in Sprague-Dawley rats with a single injection of azoxymethane. Rats were fed either a control diet (AIN-76) or the control diet to which had been added 75 mg/kg or 150 mg/kg all-trans retinoic acid. Within 4 weeks, we observed that the diets containing all-trans retinoic acid reduced the total number and multiplicity of aberrant crypt foci in the colon. However, all-trans retinoic acid increased the size of the lesions that persisted, possibly due to a greater proportion of lesions with dilated crypts. In situ hybridization and immunohistochemistry were performed on the colons for the in vivo analysis of gene expression in these lesions. The expression of myc-specific mRNA and protein in aberrant crypt foci significantly decreased with both levels of all-trans retinoic acid. In contrast, fos-specific mRNA and protein in aberrant crypt foci significantly increased when 150 mg/kg all-trans retinoic acid was added to the diet. The most important findings of this investigation are that intervention with all-trans retinoic acid in the pre-malignant stage of colon carcinogenesis is effective in decreasing the number and growth of aberrant crypt foci and altering the expression of the c-myc and c-fos genes. PMID- 8449606 TI - Combined therapy with IL-6 and inactivated tumor cells suppresses metastasis in mice bearing 3LL lung carcinomas. AB - We investigated the anti-tumor effects of human recombinant interleukin-6 (hrIL 6) on the highly metastatic Lewis lung-carcinoma clone, D122. These cells express high-affinity IL-6 receptors at numbers comparable to the IL-6-dependent murine hybridoma B9 cells; however, IL-6 did not affect D122 cell proliferation or expression of MHC-class-I antigens in vitro. In vivo, treatment of mice bearing D122 tumors in the footpads, with a low dose of IL-6 in 3 daily injections, 4 days a week for 3 weeks, significantly decreased spontaneous metastases. However, only combined treatment of IL-6 and irradiated tumor cells resulted in almost complete protection against spontaneous metastases. Histological analysis confirmed the absence of micrometastases in most of the animals treated by this combination protocol. Analysis of the cytolytic activity of splenocytes at various time points during combined IL-6 and immunotherapy of tumor-bearing mice revealed significant and sustained lysis of the poorly immunogenic D122 carcinoma cells, while splenocytes of control mice could not lyse D122 target cells. Activation of specific immunity was also demonstrated when mice were pre immunized with hrIL-6 and inactivated D122 cells and challenged with live carcinoma cells 10 days later. Significant growth inhibition of the primary tumor was observed. PMID- 8449608 TI - Tumor-necrosis factor can enhance radio-antibody uptake in human colon carcinoma xenografts by increasing vascular permeability. AB - Marked differences in the tumor uptake of a 125I-labeled monoclonal antibody (MAb) directed against carcinoembryonic antigen (CEA) were observed in 4 serially transplanted human colorectal carcinomas in nude mice. A comparative study showed that elevated values of measurable tumor vascular parameters, such as permeability, blood flow and blood volume, correlated better with high MAb tumor uptake than the concentration of target antigen in the tumor. In an attempt to modify the vascular parameters and to determine if this could increase antibody uptake by the tumor, rhTNF alpha (TNF) was injected i.t. or i.v. and antibody localization experiments were performed immediately thereafter. Results showed that the permeability of the tumor vessels increased 8 to 10 fold 1 hr after i.t. injection of TNF as compared to control tumors injected with saline. Tumor uptake of 125I-labeled anti-CEA MAb, was 3 times higher 2 hr after i.v. injection and still 27% higher 22 hr later, as compared to results from controls. Intravenous injection of TNF simultaneously with the 125I-labeled anti-CEA MAb also resulted in a 2-fold increase in tumor uptake 4 hr after injection, but the increase was no longer significant 24 hr after injection. Interestingly after i.v. injection of TNF, the MAb concentration in the blood and other normal tissues, such as liver, kidneys, lungs and heart was decreased, resulting in significantly higher ratios of tumor to normal tissue. Taken together the results demonstrate that injection of TNF can increase tumor vascular permeability and improve radio antibody uptake. This raises the possibility of increasing the radiation dose delivered by antibody to the tumor in the course of radioimmunotherapy. PMID- 8449607 TI - Inhibition by dehydroepiandrosterone of butylated hydroxyanisole (BHA) promotion of rat-bladder carcinogenesis and enhancement of BHA-induced forestomach hyperplasia. AB - The effects of dehydroepiandrosterone (DHEA) with/without ribonucleoside (RNs) supplementation on butylated hydroxyanisole (BHA) bladder-tumor promotion and forestomach carcinogenesis were investigated. Male F344 rats were given N-butyl-N (4-hydroxybutyl)nitrosamine (BBN) in their drinking water for 4 weeks and then received basal diet or diet containing BHA, DHEA, a mixture of RNs, BHA + DHEA or BHA + DHEA + RNs for 32 weeks. The occurrences of papillomas and carcinomas in the urinary bladder were increased in the groups given BHA or BHA + DHEA + RNs, as compared with control group values. In comparison with the BHA group, the BHA + DHEA group incidences and numbers of these tumors were decreased. However, the incidence and multiplicity of papillomas in the group given BHA + DHEA + RNs were again elevated. DNA synthesis levels in normal-appearing bladder epithelium, but not tumor cells, were closely correlated with the observed level of promotion in most groups. The case of DHEA alone proved exceptional in that DNA synthesis was markedly decreased without any significant influence on lesion development. In the forestomach, DHEA, which itself was associated with slight although non significant hyperplasia, enhanced BHA-induced epithelial lesions, characterized by marked basal-cell proliferation and keratin-cyst formation, independently of additional RNs administration. Our results suggest that the anti-promoting effects of DHEA in the bladder depend on a deficiency in the pentose phosphates necessary for production of nucleosides. Organ-specific modulation is indicated by the enhancing effects of DHEA on BHA-induced forestomach hyperplasia. PMID- 8449609 TI - Cell culture of tumors alters endogenous poly(ADPR)polymerase expression and activity. AB - Poly(ADP-ribose)polymerase, a chromatin-bound enzyme, actively participates in processes such as cell proliferation, differentiation, and DNA repair and replication. This enzyme is also implicated in cell transformation, and its inhibition has been proposed to potentiate anti-cancer drug activity. Since cells prepared from tumor biopsies and established tumor cell lines are commonly used to evaluate the efficiency of anticancer therapies, we have compared poly(ADP ribose)polymerase activity in animal tumor cells growing in vivo and in cell culture. Three tumor types were tested: a mastocytoma (P815), a lymphoma (RDM4), and a glioma (C6). Our results show that cell culture alters poly(ADP ribose)polymerase levels and activity. Endogenous poly(ADP-ribose) activity was several fold higher in exponentially growing cells than in cells freshly recovered from solid or ascitic tumors. Moreover, polymerase activity increased with culture time, reaching a maximum when cells became confluent. Measurements of poly(ADP-ribose)polymerase gene expression and protein amount indicate that lower enzyme activity in tumors grown in vivo are sustained by decreases in poly(ADP-ribose)polymerase mRNA and protein amount. In contrast, the increase in endogenous poly(ADP-ribose)polymerase activity observed in cultured cells was due to enzyme activation and not to de novo protein synthesis. Such differences must be considered when assessing the applicability of cell-culture results to in vivo situations. PMID- 8449610 TI - Insulin dependence of murine T-cell lymphoma. II. Insulin-deficient diabetic mice and mice fed low-energy diet develop resistance to lymphoma growth. AB - Physiological concentrations of insulin support the in vitro growth of LB T-cell lymphoma. We could not detect similar insulin dependence in other tumor cell lines. This study reports that insulin also enhances the growth of LB cells in vivo. Mice treated with Streptozotocin (SZ) developed partial resistance to LB lymphoma growth and they survived longer (p < 0.0025) than non-diabetic mice after LB-cell inoculation. A few diabetic mice developed complete tumor resistance, manifested by total regression of the lymphoma. SZ-treated diabetic mice reconstituted with external insulin died as fast as non-diabetic mice when both were inoculated with the same number of LB cells. The SZ-treated diabetic mice did not develop resistance to the growth of BCLI B-cell leukemia, which demonstrated only a marginal proliferative response to insulin in vitro. Mice fed a low-energy diet exhibited low insulin levels and also developed resistance to lymphoma growth (50% survival 21 days vs. 15 days; p < 0.0005), supporting the concept that insulin enhances LB T-cell tumor development in mice. PMID- 8449611 TI - Expression of integrins and other adhesion molecules on NK cells; impact of IL-2 on short- and long-term cultures. AB - We have investigated, using flow cytometry, the expression of 19 adhesion molecules on fresh and IL-2-activated NK cells. The study included beta 1, beta 2 and beta 3 integrins, CD2, CD54 and CD58 (belonging to the immunoglobulin superfamily), and CD44 and L-selectin (homing receptors). alpha 1 and alpha 2 of the beta 1 integrins were non-existent and alpha 3 was weak on freshly isolated NK cells, but their expression increased after 4 weeks in culture with IL-2. On the other hand, some down-regulation of alpha 4 and alpha 5 and disappearance of alpha 6 was detected. CD 11a/CD18 was upregulated by IL-2, whereas CD11b-c/CD18 were down-regulated. As a novel finding we detected beta 3 on IL-2-activated T and NK cells. CD2, CD44, CD54 and CD58 were increased by IL-2 but L-selectin was strongly down-regulated on the long-term-activated NK cells. Although IL-2 activated lymphocytes are potent tumor-lysing killer cells in vitro and therefore a potential modality in cancer treatment, the IL-2 induced changes in lymphocyte adhesion molecule expression may also lead to undesired effects, such as altered untargeted distribution and compromised migratory capacity. PMID- 8449612 TI - Camptothecin derivatives induce regression of human ovarian carcinomas grown in nude mice and distinguish between non-tumorigenic and tumorigenic cells in vitro. AB - We have recently shown that the plant alkaloid 20(S)-camptothecin and its derivatives 9-nitro-20(S)-camptothecin(9NC) and 9-amino-20(S)-camptothecin(9AC) inhibit the growth of a variety of human tumors xenografted in nude mice. In this report, we demonstrate that 9NC and 9AC effectively inhibit growth, and subsequently induce regression, of human ovarian tumors grown in nude mice. Tumor regression is accompanied by degenerative changes in the tumor cells as assessed by microscopic observations of histological sections prepared from the tumors. Parallel experiments in vitro show that 9NC inhibits in a similar manner the growth of human ovarian carcinoma cells, regardless of their ability to induce tumors when xenografted in nude mice, and induces similar morphological changes in both non-tumorigenic and tumorigenic cells, as assessed by microscopic observation. Flow cytometry studies show that 9NC-induced growth inhibition of the non-tumorigenic cells is associated with accumulation of these cells in G2. In contrast, 9NC-induced growth inhibition of the tumorigenic cells is associated with the generation of cells containing a reduced DNA content, that is, cells programmed to die. In conclusion, camptothecins appear to be cytostatic for non tumorigenic, but cytotoxic for tumorigenic cells, an important finding from viewpoints of cell biology, pharmacology and cancer chemotherapy. PMID- 8449613 TI - The prevalence of congenital orthopaedic anomalies in a rural community. AB - A rural Indian population of 50,055 was studied for the detection of congenital orthopaedic anomalies by a door-to-door survey. An incidence of 2.25 cases per 1000 population was found. Club foot was the commonest anomaly at 0.9 per 1000, followed by polydactyly and syndactyly at 0.45 and 0.38 cases per 1000. The most common anomaly found in females was a congenital short 4th metatarsal (0.24 per 1000). PMID- 8449614 TI - Computer-assisted prediction of the instability of Colles' fractures. AB - Many Colles' fractures are unstable and have a tendency to redisplace when immobilised in plaster. In an earlier study, we found a high correlation between several parameters from the initial radiographs in 267 patients and the anatomical end results. The predictive power of a new computer programme designed from the data of these patients was investigated in a further group of 107 Colles' fractures. Prediction of the final radiological position was good, especially in the least and moderately displaced fractures. We have found that the initial radial shortening, the type of fracture according to Lidstrom's classification, and the age of the patients have the greatest value in predicting whether a Colles' fracture will displace to an unacceptable degree. PMID- 8449616 TI - Kinematics of the Zielke procedure (VDS) in scoliosis. Intraoperative measurements. AB - The Zielke correction technique (VDS) has two parts, derotation and ventral convex-side compression. Both were studied by measurements made during and after the operation. Ventral derotation always creates lordosis. Lordosis can be maintained during compression by insertion of intervertebral bone blocks, or kyphosis created by omitting them. PMID- 8449615 TI - Fractures of the proximal humeral epiphysis. AB - Twenty-two patients with marked displacement of a fracture of the proximal humeral epiphysis have been treated with closed or open reduction and fixation by Kirschner wires. At an average follow-up of 6.8 years there have been good functional results in almost all patients (91.1), with better results in patients under 13 years of age particularly with less residual displacement or angulation. Since there is a greater occurrence of residual deformity and symmetria and limitation of motion in older patients, a more aggressive approach to correct the initial displacement and angulation is warranted in those over the age of 13 years. PMID- 8449617 TI - Congenital, multiple, bilateral, trigger digits in a child. AB - Congenital triggering of a digit other than the thumb is a rare. A nine year old boy has been treated for congenital, multiple trigger digits in addition to the thumb. The operative findings were only slight thickening of the flexor pulley and noticeable fusiform swelling of the flexor tendons. PMID- 8449618 TI - Radial shortening for the treatment of Kienbock's disease. AB - Twelve patients with Kienbock's disease were treated by radial shortening. Eight patients were in stage II and four in stage III. After an average of 5 years, relief of pain was satisfactory in 10 patients; 8 were in stage II before operation and 2 in stage III. Two patients were dissatisfied because they had persistent pain; both were in stage III before surgery. The range of motion improved moderately. Nonunion at the site of radial osteotomy did not occur. Radiographs at follow up showed consolidation and healing of the lunate in 2 patients, nonprogression of the disease in 9 and increase of the carpal collapse in 1. The procedure helps to prevent further collapse of the lunate especially in stage II and in some patients in stage III. PMID- 8449619 TI - Hypoxaemia after osteosynthesis of hip fractures. AB - Hypoxaemia may cause postoperative confusion after operations for hip fractures in elderly patients. Twenty-two consecutive patients, with a median age of 73 years, had fractures fixed with a sliding hip screw within 48 hours of admission. The incidence of hypoxaemia was investigated postoperatively using a pulse oximeter. We have demonstrated that this complication occurs frequently on the first day and severe hypoxaemia can be prevented by supplementary oxygen therapy. Our results support the hypothesis that postoperative confusion can be caused by hypoxaemia. PMID- 8449620 TI - Cartilage canals in the tarsal navicular of the human foetus and infant. AB - We have analysed the development of the cartilage canals in the tarsal navicular in 26 human foetuses and infants, aged between 12 weeks after gestation and 10 months, using a technique of transparentation and serial histological sections of the bone. The formation of cartilage canals starts in the first 12 to 13 weeks of gestation and can be seen by transparentation at 17 weeks after gestation. They increase in number with the age of the foetus or infant and develop a branching pattern almost to the centre of the tarsal navicular. They begin and are more numerous on the dorsal surface of the cartilage structure. PMID- 8449621 TI - Joint replacement and patient education. AB - To improve patient service and in an attempt to enhance the outcome of joint replacement an information booklet has been produced and supplied to all patients admitted for this procedure at Harlow Wood hospital. A postal questionnaire was sent to groups of patients before and after the introduction of the booklets, three months after operation. The level of patient satisfaction with the information given improved from 54% to 82%. A significant improvement was noted in the patient's understanding of the procedure and management of their joint replacement. However, only 53% of patients fully understood the possible complications of the procedure. PMID- 8449622 TI - Epiphyseal stapling for leg equalization in developing countries. AB - Epiphyseal stapling to arrest growth in the longer limb in growing children has been used in 923 cases over 26 years in the management of leg length inequality. Five hundred and three were assessed at the end of growth. Seventy-one percent had 0.5 cm to 1 cm of shortening and 80% did not need an orthosis. Although other methods are available, this technique is particularly valuable in developing countries because it needs only basic surgical facilities and the financial cost is low. PMID- 8449623 TI - Persistent bony lesions in congenital syphilis. A report of three cases. AB - We report three cases of congenital syphilis with bony lesions which were unusual because they were unilateral and asymmetrical. They did not heal with conventional penicillin treatment and they resulted in angular deformities, shortening of the limb and pseudarthrosis following pathological fractures. PMID- 8449625 TI - Osteomyelitis of the pubic symphysis due to Streptococcus anginosus. A case report. AB - An unusual case of osteomyelitis of the pubic symphysis in an insulin-dependent diabetic is reported. The infection occurred after the insertion of a penile prosthesis and the organism was streptococcus anginosus. Healing took place after wide excision and drainage, with penicillin given systemically. PMID- 8449624 TI - Atypical mycobacterium osteomyelitis of the fibula. AB - Atypical mycobacterium osteomyelitis is rare. An 81 year old woman has been found to have an osteomyelitis of the upper end of the fibula due to mycobacterium avium complex. The occurrence may be related to advanced age and chronic respiratory disease. Treatment by surgery and drugs has been successful over two years of follow-up. PMID- 8449626 TI - Osteoid osteoma of the acetabulum. AB - Osteoid osteoma of the acetabulum can be expected to cause nonspecific symptoms of hip inflammation. In a sixteen year old girl, investigation by routine radiographs and a bone scan suggested a focus of inflammation with a nidus and sclerosis of the acetabulum and overgrowth of the head and neck of the femur. Removal of the lesion by an anterior approach with dislocation of the hip gave excellent results when seen after three years with a normal gait and normal hip motion. PMID- 8449628 TI - A butterfly vertebra or a wedge fracture? AB - Two patients, who had injuries to the dorsal spine with vertebral wedging, are described. In both a compression wedge fracture was diagnosed, but a careful study of the anteroposterior radiographs showed that the presumed injury was a butterfly vertebra. This rare congenital anomaly, which is usually without clinical significance, may be mistaken for a wedge fracture unless the anteroposterior view is correctly assessed. PMID- 8449627 TI - Prognostic factors for bone metastases in breast cancer. AB - Two hundred and sixty-nine patients with breast cancer were assessed with regard to multiple parameters at the time of initial diagnosis. Over a follow-up period of 6 or 7 years, 84 patients developed skeletal metastases and in 42 they were symptomatic. Symptomatic bone metastases were related to lytic metastases and an elevated sedimentation rate. The significant parameters predisposing to the development of bone metastases were the presence of adenopathies or metastases at the time of initial diagnosis. The number of axillary nodes involved was related to the number of bone metastases, the number of spontaneous abortions, and the gonadal endocrine function. The adherence of axillary nodes was related to the number of bone metastases, an elevated sedimentation rate and the serum calcium level. PMID- 8449629 TI - Global environmental change and human population health: a conceptual and scientific challenge for epidemiology. PMID- 8449630 TI - Monitoring dominant germ cell mutations using skeletal dysplasias registered in malformation registries: an international feasibility study. AB - Using data from seven malformation monitoring systems around the world, the feasibility of monitoring fresh dominant mutations using skeletal dysplasias was explored. Based on a total of over 9.5 million births, 1500 infants with skeletal dysplasias were identified (16 per 100,000). In spite of efforts to get exact diagnoses, an average of 21% were unspecified. Comparisons of rates of specific diagnoses in different programmes suggested that classification differed. By analysing maternal age distribution, estimates were made of the proportion of fresh mutations in different subgroups: conditions regarded as dominant (achondroplasia, thanatophoric dysplasia, spondyloepiphyseal dysplasia) were estimated to consist of 58% fresh mutations--some of the remaining cases were inherited, others were probably misclassified. Among conditions regarded as recessive, only 5% were estimated to be truly dominant mutations. In the total group of skeletal dysplasias, 21% were estimated to be fresh dominant mutations and if osteogenesis imperfecta were excluded, the figure was 31%. By power analyses it was shown that equal monitoring power may be obtained by a programme covering about 45,000 births per year with intensive diagnosis of each individual case of skeletal dysplasia and a programme some three times greater where no specific diagnoses are obtained. An increasing trend in the occurrence of skeletal dysplasias was seen but probably explained by changing ascertainment. An impact of antenatal diagnosis resulting in a decrease in occurrence was also apparent in some programmes. PMID- 8449631 TI - European study of the certification and coding of causes of death of six clinical case histories of diabetic patients. EURODIAB Subarea C Study Group. AB - This study was designed to investigate the large differences in diabetes mortality rates in Europe. In each of the participating countries (France, Germany, The Netherlands, Northern Ireland-UK, Republic of Ireland, Romania, Scotland-UK, Switzerland) a random sample of certifying physicians was asked to certify the causes of death of six case histories which described the deaths of diabetic patients; the responses from an average of 220 physicians per country were analysed. These registered causes were then coded nationally and the underlying cause was compared with that following a central recoding. Overall 28% of the physicians surveyed recorded diabetes on the death certificate as the underlying cause of death--France was 25% below this overall average and Germany 21% above. The national coding of diabetes as the underlying cause of death differed from the central recoding with a comparative undercoding of almost 40% in Romania, 30% in Northern Ireland and 25% in Switzerland; in contrast, there was an overcoding of diabetes by 80% in The Netherlands and 60% in the Republic of Ireland. After adjusting for central recoding, in part an adjustment for certification habits, the national coding from this simulation study was able to explain 35% of the variation in the diabetes mortality rates. With such differences in the coding of diabetes, the currently published mortality rates for diabetes are not directly comparable between European countries; some suggestions are made for the reduction of the intercountry differences in the collection and analysis of mortality data for diabetes. PMID- 8449632 TI - The frontline of HIV1 diffusion in the Central African region: a geographical and epidemiological perspective. AB - The geographical analysis of the main data on the HIV1 epidemic in Central Africa shows a frontline which has not moved significantly since 1985. The absence of a progressive increase between the countries, demonstrating a discontinuity in space, combined with the observed human and physical continuity within the areas, raises several questions. Are the low-rate areas facing only a simple delay in the diffusion, or is there a real difference between the epidemiological patterns of HIV1 in the two areas? The last hypothesis would impose a revision of the concept of an homogeneous pattern in the epidemiology of HIV1 in Africa. The need for further research is emphasized with the aim of precisely targeting preventive intervention. PMID- 8449633 TI - Viral hepatitis and drugs: a continuing problem. AB - A seroepidemiological survey of a group of drug abusers has been carried out to determine the prevalence of hepatitis C virus and hepatitis B virus, hepatitis D virus, hepatitis A virus infection markers in sera, as well as to evaluate the role of potential risk factors. A total of 645 symptomless subjects with a history of injecting heroin were recruited as volunteers from methadone maintenance centres in Rome. For all hepatitis viruses the total figures showed high prevalence rates giving considerable viral circulation in this group. Among heroin addicts the prevalence was 63.4% for HCV, 65% for HBV, 13.3% for HDV and 50.9% for HAV. Anti-HCV prevalence correlated with serological evidence of HBV infection. A significant correlation was also found between presence of HCV antibodies and exposure time to drug addiction > 5 years earlier. The data reveal the important role played by needle sharing in the spreading of multiple infections among intravenous drug abusers (IVDA). PMID- 8449634 TI - Seroepidemiology of hepatitis B and D virus infection among intravenous drug addicts in Israel. AB - To evaluate the prevalence of hepatitis B virus (HBV) and hepatitis D virus (HDV) infection among intravenous drug addicts (IVDA) in Israel, serum samples were collected from 400 asymptomatic individuals attending a methadone clinic in Tel Aviv. Overall 5.5% were HBsAg positive, 2.4% HBeAg positive, 52% anti-HBc positive and 6.6% were positive for anti-HD. Anti-HD was identified in 18% of addicts who were HBsAg positive and in 3% who were HBsAg negative and anti-HBc positive. Strong correlation was found between positivity to HBV antibodies and age and duration of drug use. History of jaundice correlated more strongly with anti-HD positivity than with presence of antibodies to HBV. We conclude that Israeli IVDA are less exposed to HBV and HDV infection than their North American and European counterparts. PMID- 8449635 TI - A latitudinal diversity gradient in virus infections in humans in England and Wales. AB - This paper reports the presence of a latitudinal diversity gradient in reports of human viral infections in the various health regions of England and Wales. The data used in this study are reports of the laboratory diagnosis of virus infections made to the Public Health Laboratory Service Communicable Disease Surveillance Centre. Two indices of diversity were calculated from the data- Fisher's and Simpson's. Both indices were shown to correlate with latitude but not longitude. Possible mechanisms for this diversity gradient are discussed. It is suggested that such a gradient in the class of human viruses is more likely to be due to increasing environmental stress in colder climates, than to the after effects of major climatic change. PMID- 8449636 TI - Methodological considerations in case-control studies to evaluate BCG vaccine effectiveness. AB - Several case-control studies evaluating the effectiveness of BCG vaccine in the last decade have presented contradictory results like previous prospective studies. Methodological differences could explain some of the case-control study results. This study explores the possibility that contradictory results could be imputed to the choice of different series of controls. Three controls were compared for each case of tuberculous meningitis: neighbourhood, hospital and household. BCG effectiveness estimates were 86.8%, 92.0% and 29.5%, respectively. The data indicated an interaction between BCG vaccine status and tuberculous focus. This could have influenced the lower effectiveness estimates found when cases were compared with household controls. The paper discusses aspects related to case-control studies applied to evaluate BCG effectiveness such as: incubation period and sufficient time since vaccination to allow development of an immune response; the presence of a tuberculous focus among the groups of cases and controls and the interaction between focus and BCG vaccination; recall bias; and optimum selection of controls in case-control studies in the context of infectious diseases. PMID- 8449637 TI - Excess mortality after early exposure to measles. AB - The impact of exposure to measles before 6 months of age has been investigated by comparing survival to 5 years of age for exposed children and controls in an urban (Bandim) and a rural (Quinhamel) area of Guinea-Bissau. In Bandim, cumulative mortality from time of exposure to age 5 years was 34.4% among exposed children and 9.3% among controls. In a matched pair analysis, exposed children had a mortality ratio (MR) of 3.80 (95% confidence interval [CI]: 1.42-10.18) compared with controls. In an unpaired analysis using Cox' regression model to standardize for background variables (sex, measles infection, age at exposure, exposure from own household, measles vaccination), there was little change in the MR (3.84, CI: 1.55-9.48). Even after 2 years of age, the exposed children tended to have higher mortality (MR = 7.96, CI: 0.98-64.74). In the rural area, the MR between exposed children and controls was 11.39 (CI: 1.42-91.51). Limited serological data suggest that at least some of the exposed had subclinical measles. In the urban area, where two studies of early exposure have been carried out, excess mortality among exposed children corresponds to 40% and 52%, respectively, of the acute measles mortality. Since these deaths would not be associated with measles in a study of protection against death after vaccination, measles immunization may have a much greater effect on childhood mortality than has previously been assumed. PMID- 8449638 TI - Lung cancer mortality among a cohort of male chromate pigment workers in Japan. AB - In 1975, five manufacturers of chromate pigment in Japan were examined in a study of the carcinogenicity of chromates. These companies were producing lead chromate, zinc chromate, molybdate orange and/or strontium chromate. The current study covers a cohort of 666 workers involved in the manufacture of chromate pigment for at least 1 year between 1950 and 1975. The workers were followed up for 15-40 years, until 1989. Many previous reports have found an excess lung cancer risk among workers involved in the manufacture of chromate pigments and chromate chemicals. In the current study, subjects were classified on the basis of years worked, years of observation, characteristics of company, type of work engaged in for the longest period of time, and involvement in the manufacture of zinc chromate. Mortality was compared with that of all Japanese males by means of the person-year method. The route of exposure was primarily inhalation through the respiratory system. None of the results showed statistically significant differences that would suggest an excess risk for malignant neoplasms, particularly lung cancer, among workers engaged in the manufacture of chromate pigment in Japan. PMID- 8449639 TI - Neonatal tetanus mortality in coastal Kenya: a community survey. AB - In a house-to-house survey in Kilifi District, Kenya, mothers of 2556 liveborn children were interviewed about neonatal mortality, especially from neonatal tetanus (NNT). The crude birth rate was 60.5 per 1000 population, the neonatal mortality rate 21.1 and the NNT mortality rate 3.1 per 1000 livebirths. The neonatal and NNT mortality rates were higher in boys than in girls. Neonatal tetanus was not associated with mother's age, parity, or history of previous child death. The majority of the children (72%) were adequately protected at birth against NNT; in those with documented protection NNT mortality was 0, in those with undocumented protection 1.2 and in other children 8.5 per 1000 livebirths. Other risk factors for NNT included home delivery, untrained assistance during delivery, unhygienic cord cutting and application of potentially infectious substances on the umbilical stump. The survey indicates that over the past decade the surveyed area has greatly reduced neonatal and NNT mortality. Possible strategies for accelerated NNT control have been identified by the survey. PMID- 8449640 TI - Space time clustering of birth in SIDS. PMID- 8449641 TI - Oral contraceptives and fatal thromboembolism in young women. PMID- 8449642 TI - From Barbara Aronson and Irene Bertrand. PMID- 8449643 TI - Physical activity and occupational risk of colon cancer in Shanghai, China. AB - Using occupational data for over 2000 colon cancer cases diagnosed between 1980 and 1984 in Shanghai, and employment information from the 1982 census for the Shanghai population, standardized incidence ratios (SIR) were computed for occupational groups classified by job types and physical activity levels. Men employed in occupations with low physical activity levels had modest but significantly elevated risks of colon cancer. SIR for jobs with low activity based on sitting time was 121 (95% confidence interval, Cl: 108-135) and based on energy expenditure was 126 (95% Cl: 115-138). Corresponding SIR for women were 99 (95% Cl: 83-118) and 113 (95% Cl: 100-127). The data were also used to screen for specific occupations with elevated SIR to generate leads to occupational colon cancer. Increased incidence was observed for professional and other white collar workers, and male chemical processors and female textile workers. The findings add to the emerging evidence that workplace activity may influence the risk of this common cancer. PMID- 8449644 TI - Risk factors for pancreatic cancer: an exploratory study. AB - An exploratory case-control study to detect risk factors for pancreatic cancer was conducted within a large cohort of people who had received multiphasic health checkups in the San Francisco Bay Area. Four hundred and fifty who later developed pancreatic cancer were compared with 2687 who did not with respect to 779 characteristics recorded at the checkups. There was strong confirmation that cigarette smoking and diabetes mellitus were associated with risk of subsequent pancreatic cancer. Higher levels of serum iron, iron saturation and body weight were also predictive. Less striking associations of interest were with the leukocyte count, pulse rate and certain questionnaire items suggesting non specific health impairment. Past concerns about alcohol and coffee consumption were not confirmed. PMID- 8449645 TI - Bladder cancer and coffee consumption in smokers and non-smokers in Spain. AB - The association between coffee consumption and bladder cancer was investigated in a multi-centre case-control study conducted in Spain from 1983 to 1986. A total of 497 cases (438 male and 59 female) with histopathologically confirmed bladder cancer were used in the analysis along with 566 hospital controls and 547 population controls. Odds ratios (OR), adjusted for age, province of residence, occupations at risk, consumption of artificial sweeteners and cigarette smoking, did not show any association between coffee consumption and bladder cancer for either sex. However, in non-smokers and mainly in males, for current coffee drinkers the OR was 2.78 (95% [Cl]: 0.78-9.87), while for drinkers of 2-7, 8-14 and > or = 15 cups/week the respective OR were 2.22, 3.11 and 1.87 with a dose response relationship for lifelong consumption and years of exposure to regular coffee consumption. The OR in male non-smokers and current coffee drinkers were 2.36 (95% Cl: 0.62-9.05) with population controls only and 1.94, 2.58 and 1.48 for the corresponding levels of intensity of consumption (cups/week). The associations observed in non-smokers suggest the existence of a possible association between coffee consumption and bladder cancer, but are based on small numbers and need to be confirmed in larger studies. PMID- 8449646 TI - Time trends in mortality for multiple myeloma in Spain, 1957-1986. AB - We studied age- and sex-specific mortality from multiple myeloma in Spain during the period 1957-1986. The presence of birth cohort and period effects was determined using a multivariate Poisson model. From an international perspective, multiple myeloma mortality in Spain during the 1980s was in the medium range. Adjusted rates for males and females were 1.36 and 0.96 per 100,000 person-years, respectively. Multiple myeloma mortality rose exponentially during the study period, the annual increase was 11.0% in males and 10.5% in females, surpassing the increase observed in other countries. The analytical model ascribed most of this increase to a birth cohort effect. The interpretation of this phenomenon is difficult. Progressive improvements in detection and reporting, and an actual rising incidence may underlie the cohort effect. PMID- 8449647 TI - Self-assessed job satisfaction and ischaemic heart disease mortality: a 10-year follow-up of urban bus drivers. AB - Several studies have shown that bus driving is a high-risk occupation for ischaemic heart disease (IHD). In order to study contributing factors in the job, all male full-time bus drivers in the three major cities in Denmark were followed for 10 years. It was hypothesized that bus drivers who reported job strain and job dissatisfaction would have an excess risk of subsequent death due to IHD. Of 2465 bus drivers, 2045 (83%) responded to a questionnaire distributed in 1978 on psychosocial well-being and work conditions. The men had their mortality recorded during the years 1978-1988. Information on causes of death was obtained from the Danish Register of Causes of Death. Some 212 respondents died during the follow up period, 59 from IHD. Relative risk (RR) for death due to IHD and all other causes of death was calculated. As expected, we found a significantly increased risk of IHD in bus drivers working in a high traffic intensity area, RR = 1.6. In contrast to what was expected, men who reported a high degree of job satisfaction had increased risk of IHD. Those who did not look for another job had a highly significant sixfold increased risk of future death from IHD. Also those who reported never experiencing mental exhaustion after work, that their job was very varied, that their job was something special, and those who reported that they would choose the same job again, had an excess risk. Death due to other causes was positively associated with marital status only. We suggest that inconsistencies in the literature on self-assessed job strain and risk of IHD may be partly explained by the fact that studies in general have focused on absence or presence of the psychosocial factor in question. A more differentiated assessment of exposure might prove more useful. PMID- 8449648 TI - Incidence of myocardial infarction and mortality from specific causes among bus drivers in Sweden. AB - Previous studies have indicated that urban bus drivers have an increased risk of coronary heart disease. In the present investigation two separate studies were carried out. In the first study the mortality from myocardial infarction (MI), as well as from other causes for all male bus drivers in Sweden (9446), was investigated and compared to those of other employed men over a 15-year period. A 50% increase in mortality from MI was observed among drivers in Stockholm and Goteborg and Bohus counties, the two counties where the two largest cities in Sweden are situated. No increased mortality from lung cancer, any cancer (all sites combined), or from all causes combined was observed for these drivers. For bus drivers in the predominantly rural areas no excess mortality from MI, or any other cause, was observed. In the second study the incidence of MI among male bus drivers, as compared with other employed men, was studied in five Swedish counties by case referent methods. An increased incidence of first events of MI, (relative risk = 1.6, 95% confidence interval (CI) 1.1-1.9) was observed for bus drivers in Stockholm county. According to our results, urban bus drivers thus have an increased risk of developing MI. The findings also suggest that factors in the work environment of urban bus drivers may contribute to this increased risk. Factors of possible importance are job strain, irregular working hours, a sedentary job, automobile exhaust fumes, and noise. PMID- 8449649 TI - Cardiac mortality in Alaska's indigenous and non-Native residents. AB - Cardiac disease mortality in Alaska, from both ischaemic and rheumatic heart disease, is of interest given the high consumption of fish and high streptococcal disease rates in the indigenous population. Uniformly coded underlying cause-of death data for the period 1979-1988, compared with that from 1955-1965, indicated that deaths from all cardiac diseases combined, have been increasing in Alaska Natives over the past 30 years. Recent mortality from all cardiac, ischaemic, and rheumatic heart diseases in Alaska Natives were 80%, 61%, and 202% of those corresponding levels in Alaskan whites, whose cardiac mortality closely profiles US whites. Alaska Native men aged 30-45 years had higher overall mortality rates for cardiac diseases than did whites because of higher mortality rates of rheumatic heart disease and cardiomyopathy. Elderly Alaska Native men had lower rates than whites, reflecting less ischaemic heart disease mortality. The lowest levels of ischaemic heart disease mortality, less than one-third that of US whites, occurred in Alaskan Eskimos who lived in an area with documented patterns of high salmon consumption by individuals with high blood concentrations of omega 3 fatty acids. Elevated mortality from non-ischaemic heart disease and previously documented genetic markers suggest associations deserving further study. PMID- 8449651 TI - Sudden unexplained death syndrome in north-east Thailand. AB - To study sudden unexplained death syndrome (SUDS) in north-east Thailand, a mailed screening questionnaire and direct retrospective interview of relatives or witnesses of the incident was carried out in four administrative districts of Khon Kaen Province, north-east Thailand. Healthy villagers, 20-49 years, who died suddenly without explanation were identified as cases. Live healthy villagers who were age- and sex-matched with the dead served as controls. The study showed that all but one case were male with a mean age of 38 +/- 8 years. The incidence of SUDS was 38 per 100,000 men 20-49 years old per year. The peak risk was at 45-49 years. About 75% of SUDS cases had an annual income per household of less than the mean per capita income in Thailand. There were more SUDS cases in the hot season than any other season. The onset was nocturnal in 84% of cases. Presence of SUDS in family members was more frequently found in cases than in controls (P < 0.001). A history of muscle soreness, malaise and recent hard labour were seen as frequently in SUDS victims as in controls. In witnessed cases, symptoms usually lasted for a few minutes prior to death. Common symptoms or signs were respiratory (groaning, choking or coughing) and muscular spasticity or paralysis. The most consistent but yet unexplained finding in this study is the association between the onset of SUDS and the rest period. PMID- 8449650 TI - Rapid decline in child mortality in a rural area of Senegal. AB - Retrospective and prospective demographic and health data collected on the population of Mlomp (6352 people in 1985), a rural area of Senegal, show that the probability of dying before the age of 5 years declined from 350 to 81 deaths per hundred livebirths in the last 25 years. This decline is greater and faster than ever observed in Senegal. The drop in mortality mainly results from improved access to new and efficient health services--a dispensary and a maternity clinic- and from growth surveillance, health education, vaccination and malaria programmes initiated in the 1960s and 1970s. Although socioeconomic conditions have changed in the area, the influence of classical factors such as women's educational level and improvement in transportation has probably been limited. Deaths from diseases that can be prevented by immunization (such as neonatal tetanus, measles, whooping cough) are now very rare (3% of the deaths of children under 5 years during the period 1985-1989). Although the risks of dying from diarrhoea or acute respiratory infections are much lower than in other rural areas of Senegal, these are still the main causes of deaths (33% and 19% of deaths after 1 month of age). Malaria, despite its high morbidity during the rainy season, causes few deaths (4%). This reflects the success of the health education programme promoting chemoprophylaxis and early treatment of fever cases. Mlomp is one example of an African rural area where the provision of well organized health services at a reasonable cost has produced a dramatic decline in child mortality. PMID- 8449652 TI - Epidemiology of sudden unexpected death syndrome among Thai migrant workers in Singapore. AB - A total of 235 cases of sudden unexpected death syndrome (SUDS) among apparently healthy male Thai migrant workers in Singapore were reported between 1982 and 1990. Most of the deaths occurred during sleep and 13% were not sleep-related. The median age at the time of death was 33 years and the median interval between arrival and death was 8 months. These deaths occurred singly and sporadically throughout the year. Post-mortem examination revealed few abnormal findings except for haemorrhagic congestion or oedema of the lungs. There were moderate to severe intra-alveolar haemorrhages with some evidence of myocarditis or pneumonitis. Preliminary findings of serial sections of the hearts indicate evidence of anomalies in the cardiac conduction system. Epidemiological investigations showed that a family history of similar deaths and serological evidence of current or recent infection with Pseudomonas pseudomallei were significantly associated with SUDS. Extensive biochemical and toxicological investigations were inconclusive. There was no evidence of chronic deficiency in thiamine or potassium among the healthy Thai workers living and working in the same conditions as the cases, and no significant abnormalities were detected on electrocardiographic examination. As these migrant workers experienced various psychosocial problems which could stem from maladjustment to an urban environment, separation from the family, burden of debts and long hours of work, stress could be a precipitating factor for SUDS. PMID- 8449653 TI - Cancer mortality and residence near electricity transmission equipment: a retrospective cohort study. AB - Several studies in recent years have raised the possibility that exposure to extreme low frequency (ELF) electromagnetic fields may be hazardous to human health, in particular by the promotion or initiation of leukaemia and other cancers. To determine if this exposure creates a long-term hazard to the public, the mortality of a group of people identified as having lived in an urban quarter of Maastricht in which two 150 kiloVolt (kV) powerlines and one transformer substation are located was investigated. Using the Dutch population registry it was possible to identify retrospectively 3549 inhabitants of the quarter who lived there for at least 5 years between 1956 and 1981. Of these 1552 study subjects lived within 100 m of the electricity transmission equipment and were exposed to magnetic field intensity of 1.0-11.0 milliGauss. The overall standardized mortality ratio and cancer mortality ratios were either not or only slightly elevated. The study does not support previously reported associations of exposure to ELF electromagnetic fields with leukaemia, brain cancer and breast cancer. PMID- 8449654 TI - Nurse-patient interaction after training in integrity promoting care at a long term ward: analysis of video-recorded morning care sessions. AB - Morning care is a complex and problematic task for the demented patient, who has problems in understanding and coping with the situation. A training programme of integrity promoting care was given to the staff of a long-term ward and improvements of care were implemented during a 3 month intervention period. To evaluate possible effects, different parameters were used and compared with the data of a control ward. This report describes how caregivers behaved towards demented patients during morning care, before and after the training, and how patients' behaviour changed. The results are based on behaviour samples from 10 patients and 10 caregivers during 99 video-recorded morning care sessions, "double blindly" analysed. The number of coding schemes was 483, each consisting of 93 questions. The most prominent differences observed after the intervention were the increased number of opportunities to take part in decisions and activities given to the patients by the caregivers, more co-operation from patients, and finally an increase in verbal contact initiated both by patients and caregivers. It seems reasonable to suggest that when the environment was made more adequate and the demented patients could cope with it, they could use latent abilities that were not manifest in a less adequate environment. PMID- 8449655 TI - Cross-cultural testing of the "appraisal of self-care agency: ASA scale" in Norway. AB - The purpose of this study was to test the discriminant validity and interrater reliability of an instrument that measures aspects of self-care agency using Norwegian populations. The ASA scale forms A and B, which had been tested in the Netherlands previously, were translated into Norwegian and administered to two groups of elderly subjects and to a sample of geriatric nurses and nursing assistants in Norway. The subjects, one group from two geriatric rehabilitation units, and another from those living independently who were attending activity centres, completed the ASA-A scale. The nurses filled out the ASA-B scale. The results were supportive of the validity and reliability. Discriminant validity of the ASA scales was demonstrated. PMID- 8449656 TI - A comparison of nursing approaches for the promotion and management of continence in the U.K. and Denmark. AB - Incontinence is recognized as a health problem of sizeable proportions affecting a wide age range of the population. This paper compares the nursing approaches for the promotion and management of continence within the U.K. and Denmark. Semi structured interview of key health professionals within Denmark was undertaken. The information collected forms the basis for a comparison of prevalence of incontinence, clinical practice, management, education and research. PMID- 8449657 TI - Nurses' perceptions of the support of patient autonomy in do-not-resuscitate (DNR) decisions. AB - This replication of Ott's study [Ott, B. (1986). An Ethical Problem Facing Nurses: The Support of Patient Autonomy in the Do Not Resuscitate Decision. University Microfilms International, Dissertation, Texas Women's University] and McLaughlin et al.'s study [McLaughlin, T., Brown, O. and Herman, J. (1988). Nurses' Perception of the Support of Patient Autonomy in Do Not Resuscitate Situations. Unpublished Research Report] explored hospital staff nurses' perceptions of their role in supporting patient autonomy in the do-not resuscitate (DNR) decision. One-hundred and sixty-five registered nurses (RNs) participated: 93 from the Veterans Administration Medical Center and 72 from a private non-profit hospital. Ott's questionnaire had four hypothetical cases in which a DNR decision would probably be made with three questions about whose opinion would most support patient autonomy and whose opinion would actually be regarded as the most appropriate for making the DNR decision. Seventy per cent of perceptions of the person whose decision would be best able to support the patient's autonomy in the DNR decision and 51% of the people perceived to actually be deemed most appropriate to make the DNR decision were consistent with Ott's DNR Decision Model. PMID- 8449658 TI - The measurement of aggression and violence in hospitalized psychiatric patients. AB - Aggression and violence are significant clinical problems in psychiatric inpatient units. However, research exploring violent behavior is limited by the lack of an adequate research scale. This paper reports on the development and testing of the Violence Scale (VS), a behavioral rating scale which measures aggressive and violent behavior towards self, others and property. The VS has been tested in two studies of psychiatric inpatients (N = 162) and (N = 42). Tests of reliability included internal consistency, item analysis and stability. Tests of validity included content and construct validity. The psychometric results were evaluated through the application of standard statistical criteria [Carmines, E. G. and Zeller, R. A. (1979). Reliability and Validity Assessment. Sage University Press, Beverly Hills, CA; Cronbach, L. J. (1951). Coefficient alpha and the internal structure of tests. Psychometrika 16, 197-333; Nunnally J. (1978). Psychometric Theory, McGraw-Hill, New York]. Coefficient alpha was 0.91 (study 1) and 0.68 (study 2) and stability was r = 0.79 (study 1). The items met most of the established criteria for item analysis and internal consistency. In factor analysis, the items met the criteria for loading onto the three predicted factors (others, self and property). Results of predictive model testing indicated that three of the four predicted relationships were supported. Initial testing indicates the scale is moderately stable, is internally consistent, and has evidence of initial limited construct validity. PMID- 8449659 TI - A classification of nursing and midwifery shift systems. AB - A classification of 122 shift systems worked by nurses and midwives in the larger general hospitals (400+ beds) in England and Wales was made. The systems were classified along two main dimensions: the degree of flexibility for shift rostering (either regular, irregular or flexible); and the speed of rotation between night and day work (either a permanent night shift or systems of fast or slow internal rotation). This resulted in nine possible categories of shift systems. The most common shift system was a flexible day shift with a permanent night shift. Other features of the systems are discussed, e.g. the start times and durations of shifts, and the relative influence of flexible rostering on these features. This classification is a prerequisite for a further research project aimed at identifying those features of shift systems which are likely to cause the least detrimental effects for the individual nurses concerned. PMID- 8449660 TI - From diploma to degree: follow up of R.N.-B.A. graduates of Tel Aviv University. AB - The Tel Aviv University post-basic nursing program, established in 1968, was the first step of nursing academization in Israel. Since then, one-third of the nursing schools in Israel have been academized. The objectives of the present study were to document changes in the worklife of the graduates since completion of the program, to learn about the influence of the program, and to identify factors promoting or impeding study in the program. A mailed questionnaire to 709 graduates produced a 46.8% response. At the time of this study 93% were working, almost half of them in hospital. Data also showed upward mobility, with 38% employed at the institutional to national supervisor level. Recommendations include continuation of the post-basic program, expansion of the clinical content, and enhanced interaction between students, graduates and faculty. PMID- 8449661 TI - Ethical dilemmas in long-term care settings; interviews with nurses in Sweden and England. AB - With the aim of investigating ethical dilemmas arising in long-term care settings, nurses were interviewed at hospitals in southern Sweden and southern England. The interviews confirmed the occurrence of conflicts in caring for the elderly, and conflicts in the staff-patient-relative constellation. The content of the interviews was analysed with regard to prevailing principles of patient autonomy and the ranking order of preferences among those involved. PMID- 8449662 TI - NF-kappa B and Rel: participants in a multiform transcriptional regulatory system. PMID- 8449663 TI - Contractile proteins and myofibrillogenesis. PMID- 8449664 TI - The genetics of nitrogen assimilation and amino acid biosynthesis in flowering plants: progress and prospects. PMID- 8449665 TI - Molecular genetic analysis of muscle development, structure, and function in Drosophila. PMID- 8449666 TI - Retinal transplantation and gene therapy. Present realities and future possibilities. PMID- 8449667 TI - Homoplasmic and exclusive ND4 gene mutation in Japanese pedigrees with Leber's disease. AB - PURPOSE: To preliminarily examine whether mitochondrial heteroplasmy or synergism of multiple mitochondrial (mt) DNA mutations are related to the symptoms manifested in Japanese pedigrees with Leber's hereditary optic neuropathy (LHON), 90 percent of which have an mtDNA mutation at position 11778 in the NADH dehydrogenase subunit 4 (ND4) gene. This would be a first step toward clarifying why not all individuals with the 11778 mutation are affected in this ethnically unique population. METHODS: Seven ND4 11778 mutant Japanese pedigrees, including 17 maternal line members, were analyzed by restriction fragment length polymorphisms and Southern blot hybridization using mutant and wild-type sequence specific oligonucleotide probes of leukocyte DNA amplified by polymerase chain reaction. RESULTS: All of the members, regardless of symptoms, were revealed to possess only the homoplasmic ND4 11778 mutation with no other mtDNA mutation tested. On the other hand, all of the affected individuals were male, and conversely, all of the unaffected were female, except for an 18-year-old male with only peripapillary microangiopathy. CONCLUSIONS: Neither heteroplasmy of the ND4 11778 mutation nor simultaneous mutations reported in the different complex I genes can account for the variation in the clinical phenotype in our series. Taken together with the sex bias in symptom manifestation, the results indirectly suggest that an extramitochondrial factor, such as an X-chromosome-linked gene, possibly contributes to the development of optic atrophy in the Japanese LHON pedigrees tested. PMID- 8449668 TI - Measuring vision with temporally modulated stripes in infants and children with ROP. AB - PURPOSE: To determine differences in preferential looking (PL) acuities using stationary and temporally modulated stripe patterns in patients with various stages of retinopathy of prematurity (ROP). METHODS: We measured the PL acuities of 134 patients (ages 4 mo to 13 yr) with various stages of ROP. Patients were divided into six subgroups according to PL vision measured with stationary stripes: (1) equal to or better than 20/200 (n = 24); (2) worse than 20/200 to 20/400 (n = 10); (3) worse than 20/400 to 20/800 (n = 15); (4) worse than 20/800 to 20/1600 (n = 13); (5) worse than 20/1600 to 20/6400 (n = 26); and (6) worse than 20/6400 (n = 46; no stationary vision). RESULTS: In the group with PL acuity equal to or better than 20/200, no difference in vision was apparent between the two methods. In patients with acuities worse than 20/200 to 20/400, the temporally modulated PL acuities were 0.23 octave better than the PL acuities measured with the stationary stripes. The difference increased to 0.86 and 1.12 octaves in the groups with visual acuities worse than 20/400 to 20/800 and worse than 20/800 to 20/1600, respectively. The difference in the group with PL acuities worse than 20/1600 to 20/6400 was 1.69 octaves. The 46 patients with no stationary vision detected only the temporally modulated stripes. CONCLUSIONS: The results suggest that the PL acuity difference between the temporally modulated and stationary stripes increases with visual impairment. Measuring PL acuity with temporally modulated stripes is an important addition to the evaluation of severely visually impaired subjects. PMID- 8449669 TI - A second box-end scoring artifact in the Farnsworth-Munsell 100-hue test. AB - PURPOSE: To investigate and describe a hitherto unreported scoring artifact in the Farnsworth-Munsell 100-hue Test, arising from the grouping of the caps into four boxes, which causes caps near the ends of a box to score less than caps near the center of a box. This artifact is in addition to a previously reported one, which causes caps near the end of a box to score more than caps in the center of the box. METHODS: Two different statistical simulations were used to generate synthetic cap sequences, which were scored in the normal way. RESULTS: For error scores less than about 500, the new artifact, which depresses scores at the ends of boxes, was found to dominate the pattern of scores. CONCLUSION: The existing published correction for the box-end scoring artifact is inappropriate for scores less than about 500, and therefore should be applied cautiously. PMID- 8449670 TI - A model for the observer on the Farnsworth-Munsell 100-hue test. AB - PURPOSE: To use a theoretical model of the observer on the Farnsworth-Munsell 100 hue test to estimate the magnitude of random variation in 100-Hue test error scores. METHODS: The model was based upon classical signal detection theory. Results from the model were obtained by computer simulation. RESULTS: There is a fairly regular relationship between mean test scores over many tests and the standard deviation of those scores. This relationship is for practical purposes unaffected by polarity in the observer's hue discrimination and by changes in the detailed assumptions of the model. CONCLUSION: The model provides a flexible tool for further theoretical research into the 100-hue test. PMID- 8449671 TI - Focal macular electroretinogram in X-linked congenital retinoschisis. AB - PURPOSE: To study macular function of X-linked congenital retinoschisis (CRS) by focal macular electroretinogram (MERG). METHODS: MERGs were recorded with 5 degrees, 10 degrees, and 15 degrees spots in 20 patients with CRS. Seventeen patients showed foveal schisis with little or no change in foveal fluorescein angiography (Group 1), and three patients showed advanced macular changes with nonspecific macular degeneration (Group 2). RESULTS: In Group 1, a-wave amplitudes were within the normal range, but b-waves and oscillatory potentials (OPs) had mean amplitudes significantly below those for normal control subjects. The mean b- to a-wave ratios, significantly lower than in normal eyes, decreased significantly with decreasing spot size. The implicit times of a-waves, b-waves, and OPs were significantly delayed. In Group 2, MERGs were nearly nondectable. CONCLUSIONS: The macular pathology of CSR exists mainly in the middle and inner retinal layers, disturbing the fovea more than the perifovea, whereas degeneration of photoreceptors progresses in more advanced stage. PMID- 8449672 TI - Oxygen distribution in the macaque retina. AB - PURPOSE: Oxygen distribution was characterized in the macaque retina, which is more like the human retina than others studied previously. METHODS: Profiles of oxygen tension (PO2) as a function of distance were recorded in a parafoveal region about halfway between the fovea and optic disk, and from the fovea in one animal. A one-dimensional diffusion model was used to determine photoreceptor oxygen consumption (QO2). RESULTS: In the parafovea, the PO2 decreased as the electrode was withdrawn from the choroid toward the inner retina, reaching a minimum value during dark adaptation of about 9 mmHg at about 70% retinal depth, and then increasing more proximally. Approximately 90% of the oxygen requirement of the photoreceptors was supplied by the choroidal circulation and 10% by the retinal circulation. In light adaptation, there was a monotonic PO2 gradient from the choroid to the inner retina, indicating that all of the oxygen used by photoreceptors was supplied by the choroid. In the fovea, the choroid supplied almost all the oxygen in both dark and light adaptation, with a minor supply from the vitreous humor. Dark-adapted foveal oxygen consumption was lower than parafoveal oxygen consumption. Light reduced the oxygen consumption of the photoreceptors, in both regions studied, by 16-36%. CONCLUSIONS: The results show that oxygenation of the parafoveal monkey retina is similar to that previously observed in the cat area centralis. In the fovea, the oxygen distribution differs as expected considering the thinner retina and the absence of inner retinal neurons and retinal circulation. PMID- 8449673 TI - Antiproliferative effect of retinoic acid in intravitreous silicone oil in an animal model of proliferative vitreoretinopathy. AB - PURPOSE: To evaluate, in vitro, the solubility and stability of all-trans RA in silicone oil (SiO) and, in vivo, the stability and the antiproliferative effect of all-trans RA in SiO on an experimental model of PVR. METHODS: The solubility and stability of RA in SiO, in vitro and in vivo, were evaluated by HPLC. Rabbits underwent unilateral gas-compression vitrectomy and gas-SiO exchange. Rabbits received 10 micrograms (n = 17), 5 micrograms (n = 11), and 2 micrograms (n = 9) of all-trans RA in SiO, and SiO only (n = 12). All rabbits received an intravitreous injection of 150,000 fibroblasts. RESULTS: RA is stable in SiO in vitro, but some isomerization from all-trans to 13-cis was observed under light exposure. In vivo, after 1 week, trace amounts of RA in SiO were observed in the controls and in the experimental animals, suggesting a steady state between the release of RA from the SiO and from the retina to the SiO. The rate of fractional retinal detachment was significantly lower in the animals that received 10 and 5 micrograms of RA than in the controls (P < 0.05). No statistical differences were found between the eyes treated with 10 and 5 micrograms of RA. Eyes that received 2 micrograms of RA showed no difference from the control group. CONCLUSIONS: The in vivo data suggest that retinoic acid might be useful as an antiproliferative agent in human eyes. PMID- 8449674 TI - Movement of fluorescein and its glucuronide across retinal pigment epithelium choroid. AB - PURPOSE: To characterize movement of fluorescein and its glucuronide across the blood-retinal barrier. METHODS: Retinal pigment epithelium (RPE)-choroid preparations from New Zealand albino rabbit were sealed in an Ussing-type chamber in a stabilized condition for 3 hr, where movement of fluorescein and fluorescein glucuronide across the RPE-choroid was studied under a short circuit condition. RESULTS: The outward (vitreous-choroid) permeability to fluorescein determined at a concentration of 15 mumol/l was about 4 times greater than the inward (choroid vitreous) permeability (P < 0.01). The outward permeability was significantly decreased by 50-65% by metabolic or competitive inhibitors (1 mumol/l ouabain, 10 mumol/l 2,4-dinitrophenol, 100 mumol/l probenecid, 30 mmol/l hippurate, or 5 mmol/l iodipamide), whereas the inward permeability was not affected by any of the above competitive inhibitors. As the fluorescein concentration was increased from 15 to 150 mumol/l, the net fluorescein movement across the tissue indicated saturation, and a Lineweaver-Burk plot gave an apparent Km of 26 mumol/l and Vmax of 1.56 nmol/hr/cm2. The outward permeability to fluorescein glucuronide determined at 15 mumol/l was about double the inward permeability (P < 0.01) and about 1/3 of the outward permeability to fluorescein (P < 0.01). The outward permeability to fluorescein glucuronide was significantly decreased by about 50% by 1 mumol/l ouabain, 10 mumol/l 2,4-dinitrophenol, or 100 mumol/l probenecid, whereas the inward permeability was not affected by 100 mumol/l probenecid. CONCLUSION: These results suggest that the majority of the outward fluorescein movement across the tissue and part of that of fluorescein glucuronide depends on an active transport mechanism, whereas the inward movement of both fluorescein and fluorescein glucuronide occurs by a passive mechanism. PMID- 8449675 TI - Effects of a high-galactose diet on the interphotoreceptor matrix of two strains of rat. AB - PURPOSE: The authors previously reported that a diet containing 30% galactose retards the development of the late-onset photoreceptor dystrophy in the spontaneously hypertensive (SHR) rat. It was suggested that the dystrophy might result from faulty galactosylation of a critical glycoprotein or glycosaminoglycan (GAG) in the interphotoreceptor matrix (IPM). In the current study, this hypothesis was tested by studying IPM protein and GAG composition in SHR and normotensive Wistar-Kyoto (WKy) control strain rats fed a standard or a high-galactose (30%) diet. METHODS: The authors performed biochemical analyses of the IPM of SHR and of WKy control rats fed either the basal diet or a 30% galactose diet for 14 mo and labeled at the termination of the experiment with 3H glucosamine and 35S-sulfate. Analyses included high-performance liquid chromatography and two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and isoelectric focusing (IEF) of extracted proteoglycans with identification of the GAG by selective enzymatic degradation and immunoblotting of SDS-PAGE gels for interphotoreceptor retinol-binding protein (IRBP), with slot blots for additional quantitation. RESULTS: Although several differences were detected in GAG radiolabeling between the two strains, only one, a decreased overall synthesis of 3H-glucosamine-labeled GAG in the WKy rats, was altered by the high-galactose diet. There was no apparent difference in the protein patterns of the IPM as evaluated by two-dimensional SDS-PAGE and IEF. However, slot blots of that portion of the IPM extracted from the neural retinas showed less reactivity per microgram of protein for IRBP in the galactose-fed animals of both strains than for the rats fed a basal diet. This was statistically significant, however, only in the WKy rats. CONCLUSIONS: The composition of the IPM of these two strains of rat appears similar to the composition of the IPM of other species that have been studied. Whether the quantitative alteration in IRBP that appears to be produced by galactose feeding has functional significance, with particular relevance to retarding the development of the photoreceptor cell dystrophy of the SHR rat, is unclear at this time. PMID- 8449676 TI - The temporal and spatial expression of basic fibroblast growth factor during ocular development in the chicken. AB - PURPOSE: The authors determined the temporal and spatial localization of basic fibroblast growth factor (bFGF) during ocular development in the chick embryo in an attempt to elucidate its role in this process. METHODS: These studies used monospecific polyclonal rabbit anti-human bFGF immunoglobulin G in conjunction with immunohistochemical techniques and western blot analysis. Embryonic eyes at 5-20 days of development were studied. RESULTS: The bFGF was not detected by western blot analysis until embryonic day 12. However, low levels of bFGF immunoreactive material were present in pigmented and neural retina and the lenses of 5-day embryos. Lens epithelial and fiber cells remained weakly stained throughout development; neuroepithelial cells, ganglion cells, amacrine cells, and photoreceptors all contained significant levels of bFGF-immunoreactive material. Corneal epithelium consistently contained high levels of immunoreactive material. In the corneal endothelium, increasing levels of immunoreactive material were seen as development proceeded. CONCLUSION: It was hypothesized that bFGF may be involved in regulating the proliferation and differentiation of ocular cells in either an autocrine or paracrine fashion during development and that it may play a role in tissue maintenance in the adult eye. These conclusions are consistent with the temporal and spatial expression of bFGF described here. PMID- 8449677 TI - Variable oxygen exposure causes preretinal neovascularization in the newborn rat. AB - PURPOSE: To test the hypothesis that variable hyperoxia potentiates preretinal neovascularization in newborn rats, and to establish a more reliable animal model of ROP in which therapies designed to inhibit abnormal angiogenesis can be tested. METHODS: Immediately after birth, litters of Sprague Dawley albino rats and mothers were placed in an incubator containing 40% oxygen. After 12 hours, the oxygen was increased to 80% with a transition time of less than 1 min. For the ensuing 7, 10, or 14 days, the oxygen was altered between 40% and 80% every 12 hr in a stepwise fashion. Other litters were kept in constant 80% oxygen or in room air for the same three time periods. After exposure, rats were either killed or placed in room air for an additional 2, 4, or 7 days before being killed. RESULTS: When rats were killed immediately after oxygen exposure, the resulting vessel loss in rats exposed to 40%/80% oxygen was identical to that of animals exposed to 80% (vessels constituted 12.2 +/- 2.2% of total retinal area in cyclic oxygen vs 12.0 +/- 1.2% in constant oxygen). However, preretinal neovascularization subsequently occurred in 66% (63/96) of all rats exposed to cyclic oxygen followed by a room air period but in no rats (0/50) exposed to constant oxygen followed by room air. Preretinal vascular proliferation consisted of glomerular tufts of endothelial cells, or mature, lumenized vessels containing red blood cells. CONCLUSIONS: Consistency of oxygen therapy is more important than overall oxygen level in inducing retinopathy. Consideration should be given to tighter control of intended oxygen therapy in premature infants, regardless of the target saturation level. PMID- 8449678 TI - Effects of endothelin on cultured bovine retinal microvascular pericytes. AB - PURPOSE: The endothelins, a recently discovered family of peptides, include endothelin-1, the most potent vasoconstrictor known. Retinal microvascular pericytes are thought to be contractile cells analogous to the smooth muscle cells of larger vessels, but the physiologic stimulus for their contraction is unknown. We hypothesized that the endothelins might serve as such stimuli. METHODS: The intracellular free/bound Ca++ ratio increases rapidly immediately before muscle cell contraction. We evaluated changes in this ratio in cultured bovine retinal microvascular pericytes and, for comparison, three other types of ocular cells. We loaded the cells with the calcium-sensitive, fluorescent dye Indo-1. Using a laser cytometer, we monitored the time course of changes in fluorescence of individual cells in response to several putative vasoactive agents, including, in particular, endothelin-1, 2, and 3. RESULTS: Endothelin-1 (ET-1) produced a rapid rise in the free/bound Ca++ ratio, followed by a slow decline. The response occurred at ET-1 concentrations as low as 1 x 10(-12) mol/l, and was graded in amplitude and concentration dependent. After an initial application of ET-1, repeat applications yielded no response. Endothelin-2 was less effective than ET-1, and ET-3 had no effect at all, but both agents blocked the response to ET-1. Several other agents also raised the free/bound Ca++ ratio, but were substantially less effective than ET-1. When any of these agents, except for histamine, was added after even a submaximal concentration of ET-1, no response was observed, but ET-1 applied after these agents produced a large response. Histamine could elicit a rise in the free/bound Ca++ ratio after application of ET-1 to cultured pericytes. The ET-1 response occurred in Ca(++) free medium and in medium containing 10(-4) mol/l verapamil or nifedipine, indicating that the results we observed are due primarily to the release of free Ca++ from bound intracellular stores. Endothelin-1 produced a similar change in the free/bound Ca++ ratio in cultured bovine RPE cells, but not in retinal microvascular endothelial cells or lens epithelial cells. CONCLUSIONS: ET-1 is at least three orders of magnitude more effective in producing the release of free intracellular Ca++ than other agents tested. It appears to act through specific cell surface receptors, which can be blocked by prior application of other endothelin isopeptides, but not by structurally dissimilar molecules. However, with the exception of histamine, all of these agents appear to act through a common intracellular pathway, because application of ET-1 blocks the subsequent effect of the other agents tested, except histamine. Alternatively, ET-1 may be capable of desensitizing the receptors for these agents without occupying the receptor sites. Because cultured retinal pericytes are extremely sensitive to ET 1 in a response closely linked to muscle cell contraction, ET-1 must be considered a highly plausible agonist for pericyte contraction in vivo. PMID- 8449679 TI - Effects of Al3+ and Be2+ ions combined with NaF on ciliary process adenylyl cyclase activity and aqueous humor dynamics in the rabbit eye. AB - PURPOSE: The activity of Al3+, Ga3+, and Be2+ ions in the presence of NaF to directly activate G-proteins was investigated by their potentiative effect on forskolin (FSK)-activated adenylyl cyclase in rabbit ciliary process membranes and their effects on aqueous humor dynamics in vivo. METHODS: Adenylyl cyclase (AC) was determined by radiometric conversion of ATP to cAMP by the particulate fraction of rabbit ciliary processes. Intravitreal injections of sterile solutions of analytical grade salts were made into the center of the vitreous in a volume of 20 microliters. Intraocular pressure, aqueous humor flow, and uveoscleral outflow measurements were made by pneumatonometry, fluorophotometry, and fluorescein-dextran method, respectively. Outflow facility was determined by tonography in the intact eyes and by two-level constant pressure perfusion in cannulated eyes. RESULTS: Both Al3+ (EC50, 40 mumol/l) and Be2+ (EC50, 11 mumol/l) in the presence of 0.5-2 mM NaF activated the stimulatory G-protein Gs. Ga3+ was ineffective and did not antagonize the activation by Al3+. Intravitreal injections of Al3+ (1 mumol/eye) or Be2+ (0.5 or 1 mumol/eye) had no significant intraocular pressure (IOP) effect, nor did 1.5 or 3 mumol/eye of NaF, but when either cation was injected together with NaF, IOP decreased by up to 40% for up to 140 hr. At the time of maximum IOP effect (72 hr) aqueous humor flow determined by fluorophotometry was decreased in BeCl2+ NaF-treated eyes by 40% relative to BeCl2-treated eyes; however, tonographic facility of outflow was unaffected. Uveoscleral flow was also decreased by 38% in BeCl2+ NaF treated eyes. CONCLUSIONS: These findings support the hypothesis that Gs activation of ciliary process adenylyl cyclase decreases aqueous humor formation rate in rabbit eyes, and that activation of G-proteins mediates contraction of ciliary muscles causing a decrease of aqueous humor outflow via the uveoscleral route. The results suggest that G-proteins putatively involved in trabecular facility changes are less sensitive to activation by BeF3- than are other parameters of aqueous humor dynamics. PMID- 8449680 TI - Method for estimating the spheric aberration of the human crystalline lens in vivo. AB - PURPOSE: The authors describe a method for estimating the spheric aberration (SA) of the human crystalline lens in vivo. METHODS: This method was based on a comparison of the measured change in contrast sensitivity (delta log (CSF)) of the eye and the calculated change in modulation transfer function of the cornea with undilated and dilated pupils. The method assumes that the total change in visual efficiency (delta log (CSF)) in these two states is caused entirely by the SA of the eye combined with the Stiles-Crawford effect. RESULTS: Data are reported for 20 subjects (age range, 20-56 yr). SA for the whole eye was found to be positive and in the range 0-0.83 D (0-0.80 D using Stiles-Crawford apodization). The SA of the crystalline lens was generally negative and in the range 0 to -0.81 D (0 to -0.78 D using apodization). CONCLUSIONS: The method gives results consistent with previous reports in the literature. Despite potential limitations, the technique offers a new method for estimating the SA of the human crystalline lens in vivo. PMID- 8449681 TI - Comparison of specific blue and green fluorescence in cataractous versus normal human lens fractions. AB - PURPOSE: The authors compared the specific green and blue fluorescence levels in soluble and insoluble fractions (cortical and nuclear) extracted from cataractous lenses with those corresponding to clear lenses and tried to establish the nature of the role of extrinsic fluorophores in cataractogenesis. METHODS: Laser-induced fluorescence was measured with an optical-fiber sensor. The specific fluorescence was evaluated as the ratio of the fluorescence intensity to the protein concentration. Four brunescent, three pure nuclear, and four mixed nuclear subcapsular cataractous lenses were investigated. RESULTS: Specific blue fluorescence levels in cataractous fractions were similar to those in clear lens fractions, except for the insoluble nuclear fractions in which the levels were slightly lower. The specific green fluorescence in the soluble cataractous fractions showed marked increases compared with the clear lens fractions of similar ages. The insoluble cataractous fractions had similar (cortical fractions) or slightly lower (nuclear fractions) specific green fluorescence levels compared with the normal lens fractions. CONCLUSIONS: The similarity in blue fluorescence levels suggests that the blue fluorophore(s), although increasing in concentration with age, are not indicators of cataractogenesis and may not play an active role in opacification. The levels of specific green fluorescence indicate either a dramatic increase in the fluorescence quantum efficiency and/or an increase in the number of fluorescent sites per protein unit. The green-to-blue ratios were greater by a factor of as much as six in all cataractous soluble fractions versus clear ones. This suggests an accelerated formation of the green fluorescent species in cataractous tissues. PMID- 8449682 TI - Platelet-derived growth factor: receptor expression in corneas and effects on corneal cells. AB - PURPOSE: Platelet-derived growth factor (PDGF), a major mitogen and chemoattractant, is a dimeric molecule of disulfide-bonded A and/or B polypeptide chains (PDGF-AA/AB/BB). Two PDGF receptors (PDGFR) exist, alpha and beta, which dimerize after ligand exposure. The alpha-receptor binds both A- and B-chains, whereas the beta-receptor preferentially binds the B-chain. Whether PDGFR are present on, and whether PDGF is mitogenic for, corneal cells was investigated. METHODS: For receptor determination, a two-step immunoperoxidase technique with monoclonal antibodies against both alpha- and beta-receptors was applied on frozen sections of human and bovine corneas. To test the mitogenic activity of PDGF-BB, two proliferation assays, the DNA synthesis assay (3H-thymidine incorporation) and the colorimetric MTT assay, were used for cultured bovine corneal endothelial cells (BCEC) and human corneal fibroblast (HCF). RESULTS: Both receptors were present on epithelial cells, stromal fibroblasts, and endothelial cells, the beta-receptor being most abundant. In BCEC, minimal and maximal effects on DNA synthesis occurred at 10 ng/ml and 50-100 ng/ml PDGF, respectively. For HCF, the minimal and maximal effective doses were 1 ng/ml and 25-100 ng/ml of PDGF, respectively. The MTT assay, carried out in BCEC only, showed a minimal and maximal cell activity at 1 ng/ml and 10-100 ng/ml of PDGF, respectively. CONCLUSIONS: The presence of PDGFR in human corneal epithelium, fibroblasts, and endothelium and the mitogenic effects of PDGF on corneal cells indicate that PDGF may play a role in corneal wound healing. PMID- 8449683 TI - Lacrimal gland-derived lymphocyte proliferation potentiating factor. AB - PURPOSE: To determine whether lacrimal gland acinar cells are involved in modulating local immune response; to isolate and characterize a lacrimal gland factor that exerts biological activities on T lymphocytes. METHODS: A protein factor has been purified from lacrimal gland extracts by a combination of ion exchange and gel-filtration chromatography. This factor has the capacity to enhance proliferation of T lymphocytes upon stimulation with a mitogen or an antigen. We have, therefore, called this substance lacrimal gland-derived lymphocyte proliferation potentiating factor (LG-F). RESULTS: Lacrimal gland derived lymphocyte proliferation potentiating factor has a molecular weight of approximately 65,000 daltons as determined by gel-filtration and by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. T cells demonstrate greater proliferation when cultured with high concentrations of concanavalin A (Con A) in the presence of LG-F, as compared with culture without addition of LG F. This enhancing effect of LG-F may be mediated by IL-2, because the final cell count correlates with the levels of IL-2 secreted by LG-F-activated cells. Lacrimal gland-derived lymphocyte proliferation potentiating factor is nonmitogenic for T cells, but its potentiating effect is antigen-dependent. Dual stimulation of OA-primed T cells with both OA and LG-F results in greater proliferative activity, in contrast to culture with OA alone. CONCLUSIONS: The results suggest that lacrimal gland cells may interact with the immune system by elaborating nonspecific factors that modulate lymphocyte proliferation and augment lymphokine production. The presence of such a factor in the lacrimal gland may prove to be of importance in the generation of local immune responses. PMID- 8449684 TI - Acanthamoeba binds to extracellular matrix proteins in vitro. AB - PURPOSE: To identify host-tissue amoeba interactions that may be important in the pathogenesis of Acanthamoeba keratitis, the ability of the opportunistic pathogen Acanthamoeba polyphaga to bind various components of the extracellular matrix (collagen type IV, laminin, or fibronectin) was examined in vitro. METHODS: A polyphaga, isolated from a case of human amoebic keratitis, was used in the studies. In the experiments, 96-well plates were coated with 0-, 5-, 10-, 20-, or 50-micrograms/ml solutions of the basal lamina proteins laminin or collagen type IV, the extracellular matrix protein fibronectin, or casein (control). Amoeba were metabolically labeled with 35[S]-methionine, and 1x 10(4) labeled amoeba in phosphate buffered saline (PBS) were seeded per well and allowed to bind for 20 min. After washing with PBS, bound amoeba were solubilized with 1% sodium dodecyl sulphate (SDS) and scintillation counting was used to determine the number of bound amoeba. RESULTS: Counts from casein and protein-free controls were not significantly different from each other (P > 0.05). There was a significant increase in the binding of 35[S]-labeled A. polyphaga to collagen IV, laminin, and fibronectin over controls (P < 0.0001) and the binding was concentration dependent. The rank order of binding was collagen > or = laminin >> fibronectin. Alpha-methyl-mannopyranoside, but not fucose, inhibited binding of labeled A. polyphaga to collagen IV, laminin, and fibronectin in a concentration-dependent manner. CONCLUSION: In summary, the binding assays show that Acanthamoeba bind preferentially to collagen, laminin, and fibronectin, in that order, and that the adherence process is inhibited by mannose. PMID- 8449686 TI - Visual evoked response asymmetry only in the albino member of a family with congenital nystagmus. AB - PURPOSE: To examine the purported relationship between visual fiber misrouting and congenital nystagmus (CN) by studying a family containing members with either hereditary CN alone or in conjunction with albinism. METHODS: Eight relatives in three generations of a family with two genetic disorders (congenital nystagmus [CN] and albinism) underwent complete ophthalmologic examination and visual evoked potential (VEP) assessment of visual pathway organization using a luminance flash and checkerboard pattern onset/offset stimulus paradigm. Age matched controls patients (albino, CN, or normal) corresponding to the three affected family members underwent the same procedure. RESULTS: The standard VEP albino misrouting test did not reveal any signs of abnormality in all family members tested except for the clinically diagnosed 8-month-old albino proband patient. Visual evoked potential assessment from the albino patient evinced contralateral asymmetry characteristic of aberrant temporal retinostriate projections. CONCLUSIONS: Although CN and albinism share some of the same clinical symptoms, these findings indicate that the disorders may be inherited and manifested independently in members of one family. Furthermore, the functional and/or structural factors responsible for CN cannot be readily ascribed to VEP retinal-cortical misprojections recorded in albinism. PMID- 8449685 TI - Corneal endothelial modulation: a factor released by leukocytes induces basic fibroblast growth factor that modulates cell shape and collagen. AB - PURPOSE: We have previously reported that corneal endothelial modulation takes place when rabbit corneal endothelial (CE) cells are exposed to corneal endothelium modulation factor (CEMF) released by polymorphonuclear leukocytes (PMN) (Kay, E. P., L. Rivela, and Y. G. He, 1990. Invest Ophthalmol Vis Sci. 31:313-322). The modulation was involved in phenotypic switches from polygonal cell shape to fibroblastic morphology and from basement membrane collagen (type IV-rich) synthesis to fibrillar collagen (type I-rich) synthesis. In the current study, we tested the effect of several growth-modulating factors on corneal endothelial modulation. METHODS: The effect of basic fibroblast growth factor (bFGF) on cell proliferation was measured by [3H]thymidine incorporation into DNA and cell numbers. Collagen expression was determined by SDS-polyacrylamide gel electrophoresis and by Northern blot analysis. Transcription rate was determined by nuclear run-off assay. Basic fibroblast growth factor synthesis was analyzed by immunoblot assay and quantitated by ELISA assay. Immunofluorescent staining was used for in vivo localization of bFGF and its receptors. RESULTS: Basic fibroblast growth factor (bFGF) supplemented with heparin is able to modulate the same phenotypes as observed in CEMF-induced modulation. Basic fibroblast growth factor has a marked stimulatory effect on cell proliferation, as shown by increased cell numbers and [3H]thymidine incorporation into DNA. It also has a strong effect on modulation of cell morphology and collagen phenotypes; the polygonal endothelial cells are induced to assume an elongated shape, and fibrillar collagen synthesis (types I and V) is turned on by bFGF, whereas type IV synthesis is markedly reduced. Such modulating effects of bFGF are augmented by CEMF. Furthermore, CEMF significantly increases production of bFGF in CE cells; the CEMF-treated CE cells synthesized bFGF seven times more than did the control cells. The induced bFGF has a major peptide band of 18.4 kD. Immunohistochemical analysis demonstrates that rabbit corneal endothelium in vivo stains for bFGF, while Descemet's membrane requires prior digestion with proteinase K. In situ localization of bFGF receptors demonstrates that high affinity receptors for bFGF are present in corneal endothelium. However, neither transforming growth factor (TGF-beta), epidermal growth factor (EGF), nor retinoic acid (RA) alters qualitative collagen phenotypes; rabbit CE cells continue to synthesize type IV collagen as a predominant species under the influence of these factors. Unlike rabbit CE cells, bovine CE cells in culture produce predominantly fibrillar collagens (I, III, and V). Transforming growth factor enhances type III collagen synthesis and induces type I collagen, but none of these factors affects type IV collagen synthesis by bovine cells. Neither steady-state levels of collagen RNA nor relative transcription rates of the collagen genes are changed significantly by TGF-beta, EGF, or RA in either rabbit or bovine CE cells. CONCLUSIONS: These findings suggest that bFGF is able to simultaneously modulate three phenotypic aspects of rabbit CE cells (cell proliferation, cell shape, and collagen expression). Furthermore, CEMF induces de novo synthesis of biologically active bFGF, indicating that bFGF, through the action of CEMF, is the key molecule during corneal endothelial modulation, which ultimately leads to corneal fibrosis (retrocorneal fibrous membrane). PMID- 8449687 TI - Myopic children show insufficient accommodative response to blur. AB - PURPOSE: The study was performed to establish the relationship between the slope of the accommodative response function and refractive error in children. METHODS: Using an autorefractor, accommodative responses were measured in children under the following conditions. The subjects wore their best subjective refraction to view targets (a 3 x 3 array of 20/100 letters) displayed at seven distances (4.0 to 0.25 m). They viewed letters placed at 4.0 m through a series of negative lenses and letters placed at 0.25 m through a series of positive lenses. RESULTS: Myopic children accommodate significantly less than emmetropic children for real targets at near distances. Compared with emmetropic subjects, myopic children use blur poorly to increase accommodation, as shown by shallow slopes of the accommodative response functions for negative lenses. However, with positive lenses, requiring relaxation of accommodation, there is no significant difference in slope between myopic and emmetropic children. CONCLUSIONS: Blur is not an effective stimulus for accommodation in myopic children. PMID- 8449688 TI - Experimental autoimmune anterior uveitis. The preparation of uveitogenic ocular melanin. AB - PURPOSE: The purpose of this study was to develop a rapid procedure for the preparation of melanin with a specific, highly uveitogenic activity. METHODS: A crude melanosome fraction was isolated from bovine choroids (containing remnants of adhering retinal pigment epithelium). The fraction was extracted with hot 2% sodium dodecyl sulfate, and Lewis rats were immunized with the purified melanin, using pertussis toxin as coadjuvant. RESULTS: The purified melanin was free from pathogenic photoreceptor antigens and other accompanying or adsorbed proteins. It was able to evoke severe, acute, anterior uveitis with the typical characteristics of experimental autoimmune anterior uveitis (EAAU; without retinitis or pinealitis), even at the level of 1 micrograms melanin protein. CONCLUSIONS: The rapidly prepared ocular melanin exhibits the same qualities as purified choroidal or retinal pigment melanins obtained by much more laborious procedures (which also deliver other subcellular fractions for investigation). It is suitable for the study of the immunopathogenesis of EAAU, which is a new model for human acute anterior uveitis. PMID- 8449689 TI - [Pseudomonas aeruginosa folliculitis after epilation]. AB - We report on a rare case of Pseudomonas aeruginosa folliculitis following depilation of the legs in a 33-year-old woman. Recently attention has been drawn to Pseudomonas-folliculitis acquired from whirlpools. The possibility of P. aeruginosa folliculitis occurring after skin depilation is less well known. The source of infection may be contaminated cosmetics or the hospital environment. The conditions favouring Pseudomonas invasion of the skin, and the clinical picture, course and of treatment P. aeruginosa folliculitis are discussed. PMID- 8449690 TI - [Atypical mycobacteriosis in immunosuppression]. AB - We report on a 50-year-old patient with bluish swellings on the forearms and hands. These symptoms were accompanied by arthralgia. The patient treated himself with about 120 mg methylprednisolone daily, which initially resulted in only slight improvement. Microbiological investigations from cutaneous abscesses demonstrated an atypical mycobacterium (Mycobacterium chelonae). Occurrence of these bacteria is ubiquitous. In immunodeficient states infections are possible, which may be followed by dissemination of the mycobacteria in traumatic skin lesions. In the patient under discussion, dissemination was probably enhanced by the misuse of steroids. Despite chemotherapy, the patient died, perhaps as a consequence of dissemination. PMID- 8449691 TI - [Localized cicatricial bullous pemphigoid of the Brunsting-Perry type]. AB - Localized cicatricial pemphigoid of the Brunsting-Perry type is a very rare bullous condition, which has so far been reported in 51 cases. It is characterized by scarring blisters confined to the head, scalp and neck. Diagnosis can be difficult because of the discrete skin lesions, often repeatedly false-negative direct immunofluorescence, and the absence of circulating antibodies. We report on a 87-year-old male patient with the typical clinical feature of a cicatricial pemphigoid of the Brunsting-Perry type and give a review of the 51 cases published in the world literature. PMID- 8449692 TI - [Treatment of androgenic alopecia with minoxidil]. PMID- 8449693 TI - [Comment on the contribution by E. Nauroth: Consent of the patient for disclosure of a "dermatologic report" and "medical documentation of suspected occupational disease"]. PMID- 8449694 TI - [Differential diagnosis of genital fluor]. PMID- 8449695 TI - [Disappearance of the ozone layer and skin cancer: attempt at risk assessment]. AB - The increased incidence of skin cancer recorded worldwide is alarming. The incidence of malignant melanoma has doubled in Germany every 10-15 years during recent decades, for example, as documented in the population-based cancer registry of the Saarland. In 1989, the incidence was 8.3 cases/100,000 inhabitants a year equally for both sexes. Non-melanoma skin cancer (basal cell and squamous cell carcinomas) showed a similar dramatic increase like melanoma and ranged in second place in the Saarland Cancer Registry in 1989, exceeded in men only by lung cancers and in women only by breast cancer. Their incidence was 93.4/100,000 in men and 55.8/100,000 in women. Epidemiological studies worldwide revealed a correlation between the increase of skin cancer incidence and UV exposure in white populations, and Caucasians living in regions near the equator are predominantly affected by this increase. Recently, incidence values for non melanoma skin cancer in the USA were reported to be 232/100,000, whereas, for Queensland/Australia even numbers as high as 2398/100,000 (males) and 1908/100,000 (females) have been published. So far, the increase in skin cancer incidence has been related to changes in leisure time habits with increasing UV exposure. In this paper, an attempt is made to estimate any additional future risks for the development of skin cancer as a result of increasing UV radiation caused by stratospheric ozone depletion. Its reduction has been reported to be 3% over large areas of the globe (65 degrees North to 65 degrees South) according to the latest study of the United Nations Environment Programme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8449696 TI - [Photodynamic therapy of skin tumors]. AB - Photodynamic therapy (PDT) is still an experimental modality using red light in conjunction with a systemic or topical photosensitizer. The photosensitizers have a longer retention time in malignant tumors compared with the normal surrounding tissue. Irradiation with a red light at wavelength of 630 nm results in photochemical generation of cytotoxic singulet oxygen. The systemic sensitizer mostly used is hematoporphyrin derivative (HPD) and the light sources are argon pumped dye lasers, gold vapour lasers and even more simple light sources based on conventional lamps. The most important side effect of systemic application of HPD is light hypersensitivity in the UVA range, which lasts up to several weeks. Multiple studies in recent years have proved that superficial basal cell carcinomas, squamous cell carcinomas, Bowen's disease and epidemic Kaposi's sarcoma respond to systemic PDT. Up to now, however studies with greater numbers of patients and a sufficient follow-up have been lacking. Topical application of sensitizers like amino-levulinic acid (ALA) and tetraphenylporphine sulfonate (TPPS) have been used for the treatment of superficial basal cell carcinomas and squamous cell carcinomas. Possible future applications of PDT are virus papillomas and psoriasis. Even if PDT is an experimental therapeutical modality at present, it may become more clinical relevant in the future. PMID- 8449697 TI - [Skin lipids in seborrhea- and sebostasis-associated skin diseases]. AB - Recent studies suggest that epidermal skin lipids play an important role in the pathogenesis of skin diseases associated with seborrhoea or sebostasis. Depending on the state of the skin, various lipids are found in varying quantities and proportions. In some sebostatic diseases, in particular, altered enzyme activities relevant to the synthesis of lipids have been identified, which may account for alterations in epidermal lipid fractions. This concept represents a substantial modification of earlier ones, according to which sebostatic or seborrhoeic skin diseases were attributed solely to decreased or increased sebum lipids, respectively. This provides an important rationale for a new approach to the therapy of certain skin diseases with specific lipid fractions, such as ceramides. PMID- 8449698 TI - [The HLA pattern in Adamantiades-Behcet's disease in Germany. Association of occurrence, clinical symptoms and follow-up in 39 patients]. AB - The frequencies of HLA-class I antigens were studied in 39 patients with Adamantiades-Behcet's disease and were compared with those in 1415 [corrected] healthy controls; both patients and controls were of German origin. Moreover, the correlations of HLA antigens with onset, various clinical features and the course of the disease were investigated and the familial clustering of the disease was examined. We found an increased frequency of the HLA-B5 antigen in these series (P < 0.05, relative risk 2.6, confidence interval 1.2-5.5). The presence of HLA B5 was more frequently detected in male (41%, relative risk 4.9, confidence interval 1.8-13.1) than in female patients (9%; P < 0.05). A significantly higher frequency of HLA-B5 was found in male patients with severe vascular involvement, including blindness and thrombosis, than in HLA-B5-positive male patients without these features. Incidences of genital ulcers, ocular involvement, cutaneous features, positive pathergy test and of secondary symptoms as well as the age of onset and the duration of development of the complete clinical picture were all found not to be significantly correlated with any of the HLA-A, -B, -C alleles. Familial clustering was also not found in German patients. Because of the low relative risk in the presence of HLA-B5 and the lacking familial clustering, it seems likely that there is a weak immunogenetically determined predisposition for Adamantiades-Behcet's disease in Germany. HLA-B5-positive male persons of German origin show a higher relative risk to develop or acquire Adamantiades-Behcet's disease than female ones.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8449699 TI - [Munchausen syndrome. Artefacts in dermatology]. AB - Cutaneous artefacts in the presence of Munchausen's syndrome can be clearly distinguished from simulation and hypochondria. In this paper we illustrate by means of two case reports the syndrome first described by Richard Asher in 1951. Patients with artefactual disease do not want to be cured, because the artefact may be the only possible way of reacting to and making contact with their surroundings. Because of their often dramatic history the relationship between physician and patient is emotionally charged from the very beginning, which is often very difficult for the attendant physician. PMID- 8449700 TI - [Contact allergy to topical glucocorticoids]. AB - Three women with suspected contact allergies to topical corticosteroids had positive patch test reactions to amcinonide, triamcinolone acetonide and budesonide, two of them also reacted to tixocortol pivalate. Doubtful patch test results were seen on hydrocortisone and Alfasone cream. On performing a ROAT (repeated open application test) with amcinonide in all women we saw massive erythematous reactions and spreading urticaria. ROAT with Betnesol-V cream was negative. Two of the women, who were older, had multiple sensitization owing to long-term treatment of venous ulcers over many years. The third woman was young and had acquired the allergy through short-term treatment of prurigo with various topical corticosteroids. Contact allergy to topical corticosteroids is frequent and should be borne in mind in daily practice. Especially when chronic dermatitis is difficult to manage, cross reactions between chemically related corticosteroids should be considered. PMID- 8449702 TI - [Neumann type pemphigus vegetans with fatal outcome]. AB - We report on a 45-year-old patient, who first developed pemphigus vegetans of the Neumann type 9 years ago and who presented with typical manifestations of the disease 6 years after the first exacerbation. On systemic therapy with corticosteroids progression of the disease ceased. Additional application of azathioprine, cyclophosphamide or gold thiomalate, however, did not make it possible to reduce the high corticosteroid dosage without exacerbation of the disease. The long-term corticosteroid therapy led to sepsis, thrombosis of the leg and pelvic veins and osteoporosis with crush fractures of the vertebrae; corticosteroid therapy was therefore discontinued and replaced by cyclophosphamide bolus therapy associated with gold thiomalate. The subsequent exacerbation of the pemphigus was treated with methotrexate and dapsone. The skin lesions progressed further, however, and the patient died of sepsis 39 weeks after admission to the clinic. PMID- 8449701 TI - [Yellow, but healthy. Report of 4 cases of diet-induced carotenosis]. AB - Four women who had been following a "healthy" diet based on carrots and citrus fruits for some time presented with yellow-tinged skin. All four patients had high carotene levels in the blood, and three were also found to have slightly increased vitamin A levels. The other laboratory test results were normal. They were prescribed diets that did not contain carotene-rich foods, and both skin colour and laboratory tests returned to normal. PMID- 8449703 TI - Probability of causation. Implications for radiation protection. PMID- 8449704 TI - The probability that a particular malignancy may have been caused by a specified irradiation. NCRP Statement No. 7, Issued September 30, 1992. PMID- 8449705 TI - A cohort study in southern China of tin miners exposed to radon and radon decay products. AB - Several studies of underground miners have demonstrated that exposure to radioactive radon gas (more precisely, 222Rn and its short-lived decay products) at levels historically found in mines increases the risk of lung cancer. Because of small numbers of lung cancers, previous studies have had limited power to evaluate temporal and other characteristics of patterns of risk. Herein we report on a historical cohort study of male employees of the Yunnan Tin Corporation in southern China. The cohort consists of 17,143 workers with 175,143 person-years of observation and 981 lung cancer events. Eighty percent of the workers were employed underground and exposed to radon. The excess relative risk increased linearly with exposure, rising 0.6% per working level month (95% confidence interval = 0.4-0.8). In the mines, workers were also exposed to arsenic containing dusts. Adjustment for arsenic exposure, a known lung carcinogen, reduced the effect of radon exposure to 0.2% per working level month (95% confidence interval = 0.1-0.2). The excess relative risk/working level month declined significantly with attained age and with radon exposure rate as measured by the cumulative working level month divided by duration of exposure. It also declined significantly with years from last exposure and with time since exposure, but these declines were consistent only after adjustment for arsenic exposure. In this cohort, 41% of the underground workers were first exposed when < 15 y old; however, lung cancer risk did not vary consistently with age at first radon exposure. A joint analysis of radon exposure and smoking status (smoker vs. nonsmoker) rejected both an additive and a multiplicative association; the relationship was consistent with an intermediate association. PMID- 8449706 TI - Radon diffusion in model tests on Finnish esker and till soils. AB - In this paper, 222Rn activity has been investigated in some Finnish esker and glacial till areas. Model tests have been carried out to study soil parameters such as the 222Rn production rate, the 222Rn diffusion coefficients, and the 222Rn exhalation rate. The general differential equations for diffusion have been solved with different boundary conditions. Diffusion coefficients calculated from different experimental tests are comparable to each other. PMID- 8449707 TI - Liver cancer induction by 239Pu, 241Am, and thorotrast in the grasshopper mouse, Onychomys leukogaster. AB - Forty young adult grasshopper mice (Onychomys leukogaster) of both genders were injected with either 129 or 44 kBq kg-1 of monomeric 239Pu and were maintained for lifetime observation. Average liver doses to death (mean times +/- standard deviation (SD) from injection to death = 405 +/- 133 and 756 +/- 189 d) were calculated as approximately 16 and 9 Gy, respectively. These animals developed a total of 18 primary liver tumors (neoplasms, malignant, and benign). Comparison of these mice to a previously published study involving 49 control animals of the same species, 70 mice given 241Am, and 73 given Thorotrast, indicated that the liver cancer induction of Thorotrast can be attributed almost exclusively to the effects of the radioactivity and not to its nonradiation properties. This suggests that projected risks of liver cancer induction from 239Pu, 241Am, or other liver-seeking actinides in humans probably can be estimated from the liver cancer experience in Thorotrast patients using the calculated radiation doses to liver. For this species, the linear risk coefficient for induction of liver neoplasia (percent of mice with liver tumor) by 241Am or Thorotrast was estimated to be about 14.6 +/- 5.4 times the average liver dose (in Gy) for groups of animals with average liver doses of 5 Gy or less. The lowest average liver dose among groups of these mice given 239Pu was about 9 Gy, the dose was not in the linear range, and it was too high to yield reliable results for determining a risk coefficient for low dose irradiation. However, the estimates for a risk coefficient were similar for the plutonium and americium mice with liver doses of approximately 9 Gy or 16 Gy. PMID- 8449708 TI - Thorium metabolism and bioassay of mineral sands workers. AB - The concentration of thorium in the blood serum and urine of Western Australian mineral sands workers was studied to complement estimates of radiation dose derived from air sampling measurements. The concentration of thorium in urine samples from occupationally unexposed persons and pooled serum samples was also investigated. The concentration of thorium in the urine of the workers varied from 3-210 ng L-1 (geometric mean = 31 ng L-1, n = 34) while the concentration of thorium in the serum varied from 170-2,000 ng L-1 (geometric mean = 480 ng L-1, n = 25). No correlation was found between the bioassay results and cumulative airborne thorium exposure. The geometric mean ratio of daily excretion of thorium in urine to total thorium in the serum pool was 2.5%, considerably lower than the value of 10% proposed by the ICRP. These data indicate that more information is required to clarify the biokinetic models for thorium and that doses assessed from air sampling data must be interpreted with caution. PMID- 8449709 TI - 137Cs concentration in soil, prairie plants, and milk from sites in southern Chile. AB - Soil, prairie plants, and milk samples were collected at 39 dairy farms in the 9th and 10th Region in Southern Chile (38 degrees 44'-41 degrees 08' S) between 1982 and 1990. 137Cs concentrations found in soil, plant, and milk samples ranged from 3.8-17.1 Bq kg-1 for soil, from < 0.3-20 Bq kg-1 dry mass for plants, and from 0.10-0.71 Bq kg-1 for milk. Cesium concentration levels resulting from soil sample measurements exhibit a close similarity with corresponding values found in soils from Central Europe before 1986. The concentration ratio prairie plants:soil ranged from 0.05-0.62, 0.52-5.0, and < 0.02-0.40 corresponding to Dystrandepts, Placandepts, and Palehumults soil groups, respectively. At seven selected dairy farms in the vicinity of Valdivia city (10th Region), soil, prairie plant, and milk samples were taken yearly during the grazing period between 1982 and 1990. Results obtained from soil samples taken after April 1986 show no significant increase of the 137Cs concentration. Concentrations in plants and milk for 137Cs decreased during the observation time. 134Cs (as an indicator of Chernobyl fallout) was not found in soil, plant, or milk samples during 1986 1990. PMID- 8449711 TI - Safety considerations for simultaneous multiple wavelength exposure in scanning laser ophthalmoscopes. AB - A method has been developed for calculating the maximum permissible exposure for multiple wavelength lasers used in scanning laser ophthalmoscope systems. The method is based on the assumption that when the human eye is simultaneously exposed to multiple wavelength laser light, the thermal and photochemical effects on the retina are additive and independent of each other. A linear addition method is used to calculate multiple laser maximum permissible exposures for scanning laser ophthalmoscope systems. This paper also includes a discussion of possible synergistic effects of retinal biological effects caused by multiple laser exposure. An example is given to illustrate a conservative, theoretical approach to estimating the maximum permissible exposure for simultaneous multiple wavelength laser exposure. PMID- 8449710 TI - Radioactive contamination of the Adriatic Sea by 90Sr and 137Cs. AB - Results of systematic long-term measurements of 90Sr and 137Cs in surface seawater, performed at four locations along the Croatian coast of the Adriatic Sea, are summarized. Observed trends in annual mean activity concentrations are discussed. 90Sr and 137Cs fallout activities affect seawater activity, the coefficient of correlation between 90Sr fallout activity and 90Sr seawater activity being 0.72. No significant variations of 90Sr mean residence time in the sea-mixed layer on different locations were found. From 1978-1985, the 137Cs:90Sr activity ratio in seawater was 1.52 +/- 0.40. In May 1986, as the consequence of the Chernobyl nuclear accident, this radio increased to 92.4 +/- 58.2. PMID- 8449712 TI - Long-term environmental trends: selection of sampling locations in a reactor aquatic cooling system. AB - The study objective was to determine whether environmental radionuclide accumulations were occurring in an aquatic system with a 13-y history of supplying a power plant with reactor-cooling water as well as receiving plant discharge. The aquatic system consisted of the following: 1) a reactor-cooling lake; 2) a secondary lake approximately 8 km downstream; and 3) a small stream that interfaced with the two lakes. Gamma-emitting radionuclides were identified and quantified in samples of benthic sediments obtained from representative areas of the aquatic system. This study demonstrated that in a reactor-aquatic cooling system, the component of the aquatic system most likely to experience radionuclide accumulation will not necessarily be the reactor-cooling lake, but will be that component of the aquatic system whose benthic sediments contain the highest concentrations of organic matter. Further, it was shown that the quantity of oxidizable organic matter present in a sediment is a good predictor or marker for potential sites of radionuclide accumulation (i.e., 60Co and 137Cs). PMID- 8449713 TI - 60Co activity in 192Ir seeds. AB - The decayed sources of steel-sheathed 192Ir seeds have shown residual 60Co activity. The gamma spectra from such sources show the two distinctive peaks for 60Co, whereas the platinum-sheathed 192Ir sources do not show such peaks. This may be due to the low percentage of cobalt present in the magnetic alloy sheath. Though this would not affect the clinical dosimetry, it may be of concern when handling large numbers of such sources for disposal. PMID- 8449714 TI - Managing radioactively contaminated infectious waste at a large biomedical facility. AB - Proper management of infectious waste containing radioactive material depends on three program elements. First, screening methods are required to identify medical waste containing radioactive material. Second, a means of managing the volume of waste identified has to be developed. Management includes identifying the radioisotopes, dealing with the physical requirements of the waste (e.g., the need for cold storage), and treating the material as a mixed waste. Finally, methods to limit production of waste at its source must be implemented. This includes educating the radioactive material users, enabling them with the means of reducing waste volume, and giving them feedback on how well they are implementing the waste reduction practices. PMID- 8449715 TI - Computer-assisted management of liquid radioactive waste at the University of California, San Diego. AB - Commercially available software has been obtained and internal software applications have been developed to implement a tracking system for liquid radioactive wastes. This system utilizes a number of data bases that maintain sampling, waste pickup and disposition information based on various parameters. Computerization has allowed access to summary information and inventory totals that are necessary for radioactive materials license compliance. Comparative reports, which are used to show trends and track historical information, can also be generated. PMID- 8449716 TI - Breast cancer incidence at a nuclear facility: demonstration of a morbidity surveillance system. AB - In order to provide a timely means of identifying new or unexpected toxicities which may occur as a result of occupational exposures, the United States Department of Energy is currently developing a system of routine morbidity surveillance at selected nuclear facilities. Examination of surveillance data at the Hanford Site identified a possible increase in breast cancer incidence (based on three observed cases) among women working in the nuclear trades compared to all other women at the site (relative risk = 3.1; exact 95% confidence interval = 0.7-9.7). This triggered a more detailed investigation using a nested case control design and individual dosimetry readings. Information on nineteen breast cancer cases occurring at the site between 1984 and 1989 and 71 matched controls were abstracted from existing occupational medicine, administrative, and health physics records. Summary variables for cumulative, average, and peak external radiation dose equivalents were calculated after allowing for 1 y and 10 y induction and latency periods. There was no evidence that the observed excess was due to radiation exposure. Since the surveillance system is designed to be ongoing, continued monitoring of breast cancer rates in this occupational group will be carried out, and more appropriately detailed studies begun if consistently elevated rates are observed. PMID- 8449717 TI - A survey of the Czechoslovak follow-up of lung cancer mortality in uranium miners. AB - The major Czechoslovak cohort of uranium miners (S-cohort) is surveyed in terms of diagrams illustrating dependences on calendar year, age, and exposure to radon and radon progeny. An analysis of the dose dependence of lung cancer mortality is performed by nonparametric and, subsequently, by parametric methods. In the first step, two-dimensional isotonic regression is employed to derive the lung cancer mortality rate and the relative excess risk as functions of age attained and of lagged cumulated exposure. In a second step, analytical fits in terms of relative risk models are derived. The treatment is largely analogous to the methods applied by the BEIR IV Committee to other major cohorts of uranium miners. There is a marked dependence of the excess risk on age attained and on time since exposure. A specific characteristic of the Czechoslovak data is the nonlinearity of the dependence of the lung cancer excess risk on the cumulated exposure; exposures on the order of 100 working level months or less appear to be more effective per working level month than larger exposures but, in the absence of an internal control group, this cannot be excluded to be due to confounders such as smoking or environmental exposures. A further notable observation is the association of larger excess risks with longer protraction of the exposures. PMID- 8449719 TI - Diagnostic radiopharmaceutical dose estimate to the Australian population. AB - The annual per caput effective dose and the genetically significant dose to the Australian population, arising from the practice of nuclear medicine, were estimated from the results of a survey of all major hospitals. The survey was conducted for a 4-wk time period during June-July 1991. Patients were characterized by age and gender. The use of diagnostic radiopharmaceuticals resulted in values of 64 microSv and 26 microSv per caput for effective dose and the genetically significant dose, respectively. The effective dose has shown a marked increase in the last decade. These values may be compared to the estimated 2 mSv from natural background radiation. PMID- 8449718 TI - Prospective study of the clinical symptoms of therapeutic whole body irradiation. AB - Thirty-one selected patients with various haematological malignancies who received a 10 Gy-4 h total body irradiation (TBI) at the Institut Gustave Roussy 24 h before high dose cyclophosphamide for bone marrow transplantation, were prospectively evaluated for gastrointestinal symptoms, body temperature, consciousness, headache, xerostomia, parotiditis, ocular symptoms, blood pressure, and respiratory and cutaneous signs for 24 h. In spite of prophylactic administration of various anti-emetic agents, 90% of the patients experienced nausea and 80% experienced vomiting. An almost constant body temperature peak--up to 40.8 degrees C--was registered 6 h after the start of irradiation. No drowsiness was reported since the introduction of the new anti-emetic agent Ondansetron. Nearly half the patients (42%) complained of headache. The proportion of patients experiencing early (during TBI) xerostomia was 61%. 74% of patients complained of parotiditis in the first 24 h. Although this low dose rate whole body irradiation is not likely to be exactly replicated in many accidental human exposures, the incidence rate and the time-course of the observed prodromal phase symptoms may prove helpful for early triage in the case of accidental irradiation. PMID- 8449720 TI - Estimating past exposure to indoor radon from household glass. AB - CR-39 plastic was attached to household glass objects to learn whether residual radioactivity from radon decay products could be measured and correlated with cumulative radon exposures over defined time periods. Such an approach could be used to increase the completeness of exposure data collected in epidemiologic studies of residential radon. Inability to estimate radon concentrations for all residences adversely effects statistical power and thus the ability to detect an effect of radon exposure on lung cancer risk. A feasibility study was performed to determine if affixing CR-39 surface monitors to selected glass, ceramic, or enameled objects provided comparable estimates of past residential radon exposure to those obtained from year-long ambient alpha track-etch measurements. The CR-39 measurements of alpha activity in the surface of selected objects correlated with ambient radon measurements (R2 = 0.48) provided that reliable information was obtained on the history and age of the objects. This technique has now been incorporated into an epidemiologic study of radon and lung cancer to more fully estimate past exposure to indoor radon. PMID- 8449721 TI - Airborne 222Rn concentration in Cypriot houses. AB - Studies from a pilot survey in 89 houses in Cyprus show that the arithmetic mean for the housing stock is about 7 Bq m-3 and the annual effective dose equivalent to the population from radon progeny is < 330 microSv y-1. Four houses have values > 30 Bq m-3, corresponding to two standard deviations from the mean value. The highest value recorded was 78 Bq m-3. These results are considerably lower than those of other countries reported in the literature. Radon concentrations in houses is correlated to the local geology. The highest concentrations are in houses built on Chalk formations with an average value of 9.29 Bq m-3 (standard deviation 19.69 Bq m-3). The lowest concentrations are in houses built on Olivine Basalt formations with an average value of 0.50 Bq m-3 (standard deviation 0.80 Bq m-3). PMID- 8449722 TI - Electret ion chamber radon monitors measure dissolved 222Rn in water. AB - This paper describes a simple and relatively inexpensive method of determining the concentration of dissolved 222Rn in water. The method involves a recently developed electret-passive environmental radon monitor, which uses an electret ion chamber. The procedure consists of sealing a known volume of a carefully collected water sample with one of these monitors in an exposure container and determining the average equilibrium 222Rn gas concentration in the air phase during the exposure time period. This average concentration can then be used to calculate the 222Rn concentration in the original water sample. Identical samples were analyzed both by this new method and by a standard liquid scintillation method, and the results were compared over a wide range of 222Rn concentrations. There was good agreement except that the electret ion chamber method gave results that were consistently lower by about 15%. This bias in the results was attributed to both 222Rn losses during sample handling and possibly to some errors in the assumptions made in the theoretical model. A correction factor is recommended to bring the results of this technique into agreement with the standard method. The procedures are simple and economical and can be easily employed by many primary 222Rn-measuring laboratories currently using these monitors for measuring indoor 222Rn. PMID- 8449724 TI - Evaluation of a new high-density shielding material. AB - A new high-density material is evaluated for use as shielding at medical radiation therapy facilities. The substance is supplied in the form of prefabricated interlocking blocks that contain steel scrap as the aggregate in a matrix of Portland cement. This material, called Ledite by its manufacturer, permits the dimensions of radiation therapy room walls to be reduced by a factor of approximately 2 when compared with rooms made from ordinary concrete. The neutron absorption required for high-energy linear accelerators is present. PMID- 8449723 TI - A comparison of techniques in the assessment of chest wall thickness and composition. AB - The thickness and composition of defined regions of the anterior chest wall are important factors in the assessment of pulmonary plutonium by low-energy x ray counting. Estimates of these quantities are reported for seven male subjects investigated by three laboratories using ultrasonic methods and by a fourth laboratory using magnetic resonance imaging. No important bias was found in any one laboratory's estimates of chest wall thickness relative to those of the others, but differences of up to 6 mm were noted for individual subjects. The discrepancies are believed principally to reflect the different sampling regimes adopted to reach a representative mean chest wall thickness over the region of interest from measurements at selected points. The adipose-tissue component was consistently found to be lower when assessed by magnetic resonance imaging compared with estimates by ultrasound, but the differences were unimportant in the context of plutonium assessment. PMID- 8449725 TI - The scientific base for the disposal of spent nuclear fuel. AB - The main objectives of the Swedish expert seminar on spent nuclear fuel disposal were to identify those safety questions for which there is, or will be, a definitive answer, and to establish the degree of uncertainty surrounding those questions which still cannot be satisfactorily answered. The opinion was that the geological environment of the repository can be defined and its behavior predicted with much confidence, assuming the existing environment remains stable. Thus in the short term (a few hundred to thousands of years), the situation is favorable for safe disposal of spent fuel. In the longer term perspective, it was considered necessary to further investigate the evidence of the geologically recent past to predict future changes. PMID- 8449726 TI - Preliminary indoor radon investigations in Lublin region, Poland. AB - Indoor air radon concentrations in all kindergartens and play schools in Lublin, Poland, were determined in grab samples by using alpha scintillation cells. In addition, some public buildings and homes in Lublin and several places in Eastern Poland were surveyed for radon. For kindergartens and play schools, the geometric mean was 23 Bq m-3 with a standard deviation of 1.4 Bq m-3, while in public buildings and homes, these values were 26 and 1.6 Bq m-3, respectively. PMID- 8449727 TI - Initial study of 210Pb in indoor air. AB - An exploratory program was undertaken to determine the feasibility of measuring the indoor air concentration of 210Pb. Low flow rate pumps and membrane filters were used to collect samples in an office. The air filter samples were stored for 1.6 y and 210Po was chemically separated and measured by alpha spectrometry. Unsupported 210Po was also determined in air samples collected at a later time. The average air concentrations were 150 microBq 210 Pb m-3 and 12 microBq 210Po m 3. The average indoor to outdoor ratio of 210Pb in air is estimated to be 0.25. PMID- 8449728 TI - Verification of aquatic dilution factors for liquid effluents released from a nuclear power plant. AB - Dilution factors for liquid effluents released from the Fermi 2 Power Plant into Lake Erie were verified using updated liquid effluent release data, and currently available aquatic dispersion models. A near-field dilution factor of 5 currently used by Fermi 2 appears to be a reasonable assumption as supported by two models and site-specific data. Previously assumed dilution factors for shoreline points outside the near field are of the same order of magnitude as those calculated by this study. The dilution factor of 77, currently used by Fermi 2, at the Monroe water intake point is very conservative when compared with values calculated by this study. More accurate values could be generated by tracer studies as recommended by Regulatory Guide 1.113. Such studies can predict plume behavior and are more accurate than aquatic models. These new values would probably be less conservative than those currently in use, and their use would make it less likely that Fermi 2 will reach technical specification limits for liquid effluent dose. PMID- 8449729 TI - Misstatement on radium dial workers by Puskin et al. PMID- 8449730 TI - Standardizing minimum detectable amount formulations. PMID- 8449731 TI - Comparison of criteria to define radon-prone areas. PMID- 8449732 TI - Labour policy. Going forward from the Black report. Interview by Nick Robin. PMID- 8449733 TI - Health visitors' perceptions of their role. AB - A new era of demonstrable cost effectiveness in the health service has made health visitors more nervous, perhaps, than any other group of health workers. Their job involves 'unquantifiable' activities like support, prevention and health promotion. The irony is, that these activities are every bit as vital as they are hard to measure, writes Michael Traynor. PMID- 8449734 TI - Cancer prevention: how you can help. PMID- 8449735 TI - Under fives. Learning to be strong. PMID- 8449736 TI - Raising public awareness of child abuse issues. AB - Lincolnshire area child protection committee focused its 1991 public awareness campaign on verbal abuse of children. Mary Dundon and Angela Bates report on the success of the campaign: 'What do children hear? harsh words hurt--kind words help', and the lessons learned for future initiatives. PMID- 8449737 TI - Setting the agenda in health visitor/client interviews. AB - The first home visit is vital to the future relationship between health visitor and client, writes Allison Worth. Here she analyses the degree to which the client and the health visitor influence the agenda during an ante-natal visit to a 28 year old single woman six months pregnant with her first child. PMID- 8449738 TI - The Bournville playscheme. PMID- 8449739 TI - Dangerous liaisons. PMID- 8449740 TI - The Ellis-Van Creveld Foundation. PMID- 8449741 TI - No room for quality. PMID- 8449742 TI - Stir it up. PMID- 8449743 TI - Contraceptive services target youth. PMID- 8449744 TI - GP fundholding. A tale of two teams. PMID- 8449745 TI - GP alignment threatens care. PMID- 8449746 TI - Hands-on therapy. AB - Touch is a primary need for babies to develop as healthy human beings, writes Suzanne Adamson. Here she describes the success of her baby massage class, run as part of her health visitor remit. PMID- 8449747 TI - Developing an integrated strategy to meet homeless families' health needs. AB - Homeless families are vulnerable to considerable health problems, yet are overlooked in the government's national strategy for health. Access to services and contact with agencies are difficult for people displaced to a new area. Helen Lee and Ann Goodburn describe the health visiting service they offer homeless families in Camden, north London, where the majority are from outside the borough and many recent immigrants to this country. PMID- 8449748 TI - Male infertility: artificial insemination by donor. AB - It is now known that in about 40 per cent of couples attending infertility clinics, it is the man who has the underlying problem. Jacquie Cox looks at artificial insemination by donor as an alternative to treatment for infertility. PMID- 8449749 TI - A community nursery nurse working with families with multiple births. AB - The introduction of skill mix into the health visiting services is causing debate and some concern among health visitors. Patricia Marks describes a three year project in Brighton health authority in which a community nursery nurse was introduced to work in the home with families with multiple births. The role of the community nursery nurse is different from that of the health visitor but this extra input to these families has relieved pressure on health visitors' time, as well as being of tremendous help to the families. PMID- 8449750 TI - A feminist perspective on postnatal depression. AB - Many women will experience postnatal depression (PND) after the birth of their child and will receive treatment which is generally medically prescribed. The definitions and treatment of PND to a great extent remain in the hands of the medical profession: an area dominated by men, where PND is usually perceived as an individual illness. Christine Jebali explores from the alternative viewpoint of feminist theory PND as a condition exclusive to women. PMID- 8449751 TI - Preventing breakdown in women's mental health. PMID- 8449752 TI - Homes above all. PMID- 8449753 TI - Accident prevention. Getting the message across on safety. AB - Child accident prevention is a key part of the health visitor's role. But faced with the demands of a large and busy caseload, health visitors may not be able to give the subject the priority it needs. Cheryll Adams describes a uniquely simple way to ensure that parents get the message about child safety. PMID- 8449754 TI - Mixed venous oxygen saturation and oxygen partial pressure as predictors of cardiac index after coronary artery bypass grafting. AB - OBJECTIVE: To determine the relationship between the mixed venous oxygen saturation (SvO2) and the cardiac index (CI) in individuals during the first 8 hours after coronary artery bypass grafting. DESIGN: Descriptive with a correlational design. SETTING: Cardiac intensive care unit at a university medical center in the midwestern United States. SUBJECTS: Twenty-one subjects (16 men and 5 women) undergoing coronary artery bypass grafting. OUTCOME MEASURES: SvO2, thermodilution cardiac output and CI measured every 2 hours during the first 8 hours after surgery. INTERVENTION: Elective coronary artery bypass grafting. RESULTS: Significant (p < 0.05) but moderate correlations between SvO2 and CI were found only at 6 and 8 hours after surgery (r = 0.66, p = 0.001; r = 0.44, p = 0.47). Secondary analysis determined that in subjects without lung disease, mixed venous oxygen tension (PvO2) had significant correlation with CI at all data collection times (r = 0.54 to 0.72; p = 0.003 to 0.02). CONCLUSIONS: The results of this study indicate that immediately after coronary artery bypass grafting, SvO2 cannot reliably predict CI. Although statistically significant results were found for the correlation between PvO2 and CI at all data collection times, the correlations were too low to support the use of the PvO2 as a reliable clinical predictor of CI without further study. PMID- 8449755 TI - Routine invasive hemodynamic monitoring does not increase risk of aortic graft infection. AB - OBJECTIVE: To determine whether invasive hemodynamic monitoring resulted in an increased rate of aortic graft infection. DESIGN: Retrospective review with establishment of late follow-up. SETTING: Two referral teaching community medical centers. PATIENTS: Three hundred thirty consecutive patients who underwent elective aortoiliac (174), aortofemoral (91), or aortic tube (65) prosthetic graft placements during a 6-year period at the two institutions. All patients had percutaneous pulmonary artery catheter and radial artery cannula placement before surgery. Monitoring catheters were routinely removed within 72 hours. OUTCOME MEASURES: Early and late complications of catheter placement, perioperative morbidity and mortality, and late graft-related complications. RESULTS: Eighteen (5%) patients died in the perioperative period. Less than 2-year follow-up was possible in 67 patients. The remaining 245 patients were observed from 2 to 9 years (mean, 4.4 years). Graft infection was not identified in any patient. CONCLUSION: Routine invasive hemodynamic monitoring was not associated with an increase in the rate of prosthetic aortic graft infection. PMID- 8449756 TI - An exploration of the role of social networks in cardiovascular risk reduction. AB - OBJECTIVE: To identify and describe the role of social networks in influencing individual wellness motivation within the context of cardiac rehabilitation. DESIGN: A naturalistic design was used in the collection and analysis of inductively generated data. SAMPLE: Twenty-four individuals who were participating in an outpatient cardiac rehabilitation program. Of the 24 subjects sampled, 17 were men and seven were women. The respondents' ages ranged from 38 to 79 years, with a mean age of 58 years. At the time of the study, informants had been involved in cardiac rehabilitation for an average length of 10 weeks. RESULTS: Two primary categories were identified that describe informant perception of the role of social networks in motivating health behavior change: enabling and limiting. Subcategories identified were consistent with the general types of support described in social support literature (emotional, feedback, problem solving, instrumental), as well as behaviors found to diminish motivation in cardiovascular health behavior (value conflict, boundary maintenance). CONCLUSIONS: Findings from this study provide a better understanding of the role of social networks in motivating health behavior change within the contest of cardiac rehabilitation. PMID- 8449757 TI - Mediastinitis caused by Aspergillus fumigatus with ruptured aortic pseudoaneurysm in a heart transplant recipient: case study. AB - The case of a heart transplant recipient with a ruptured aortic pseudoaneurysm caused by an Aspergillus fumigatus mediastinitis is reported. Contamination of surgical fields occurring by air seeding during surgery appears to be the most probable source of infection. Subtle infectious signs of the wound and subacute course are remarkable features of this case. PMID- 8449758 TI - Abnormal permanent pacemaker inhibition by a magnet: a case study. AB - Permanent pacemaker evaluation with a magnet is an essential and widely practiced procedure used by cardiologists and electrophysiology nurses for routine pacemaker follow-up. It is generally safely performed. We present a case of a prolonged period of pacemaker inhibition in a pacemaker-dependent patient after routine magnet placement over her permanent pulse generator. PMID- 8449759 TI - The needs of family members of organ and tissue donors. AB - OBJECTIVES: To identify the needs of family members of organ and/or tissue donors during the events of organ donation. DESIGN: Retrospective, exploratory, descriptive. SETTING: Eastern Canada. PARTICIPANTS: Seven families who had consented to organ and/or tissue donation in 1988 were interviewed in their homes, 10 to 15 months after the sudden and unexpected loss of their loved one. The sample represented nine individual family members whose relationship to the donors included three mothers, two fathers, one husband, two wives, and one sister. All families consented to organ and/or tissue donation within 1 hour to 3 weeks of the donors' admission to a critical care unit. The donors' ages ranged from 16 to 41 years. RESULTS: The needs of these family members were identified from a secondary analysis of the interview transcripts from an original study on stress and coping. Their major needs included receiving information and support from health professionals, being able to visit frequently, and consenting to the organ or tissue donation. Family members identified nurses as being informative and genuinely supportive, clearly suggesting that they have the necessary therapeutic skills to approach families about donation. CONCLUSION: The need for potential donor families experiencing a critical illness phase to receive information and emotional support and to visit frequently were consistent with literature findings on other families of critically ill patients. Equally important for donor families was their need to consent to organ and/or tissue donation, which clearly indicates that health professionals need to offer the option of donation. PMID- 8449760 TI - Nurses' ability to achieve hyperinflation and hyperoxygenation with a manual resuscitation bag during endotracheal suctioning. AB - OBJECTIVE: To examine nurses' ability to deliver 1.5 times the ventilated tidal volume at 100% FIO2 with a manual resuscitation bag during endotracheal suctioning. DESIGN: Prospective, descriptive. SETTING: Six adult critical care units in a large university-affiliated medical center. SUBJECTS: One hundred nurses randomly selected from the six adult intensive care units. OUTCOME MEASURES: Nurses' manual resuscitation bag delivery of tidal volume and oxygen, as well as bagging rate, number of breaths delivered, and number of suction catheter passes performed. Patients' heart rate, mean arterial pressure, and arterial oxygen saturation. RESULTS: The mean FIO2 delivered was 0.71 (range 0.24 to 0.97). Oxygen liter flow and nurses' delivered minute ventilation predicted 24% of the variance in FIO2 delivered. Mean bagging rate was 31 compressions per minute. The mean volume per breath delivered was 626 cc, which resulted in achievement of 57% of the standard (1128 cc). Volume achieved was related to patient lung compliance, but not related to nurses' experience, unit of employment, hand strength, or size. CONCLUSIONS: Nurses observed were unable to meet the standard for volume or oxygen delivery. However this did not affect the patient's heart rate, mean arterial pressure, or SaO2. PMID- 8449761 TI - The treatment of hypoalbuminemia in the critically ill patient. AB - Hypoalbuminemia is a common finding in critically ill patients. It has been well documented that hypoalbuminemic patients have a higher morbidity and mortality rate when compared with patients with a normal serum albumin. Consequently, hypoalbuminemic patients are commonly treated with exogenous albumin in the hope of improving their outcome. There is, however, very little evidence that this practice is of any benefit. In this article the physiology of albumin in health and disease is reviewed, and those clinical studies that have investigated the use of albumin in acutely ill hypoalbuminemic patients are evaluated. PMID- 8449762 TI - Low-dose dopamine in critically ill oliguric patients: the influence of the renin angiotensin system. AB - OBJECTIVE: To assess the effect of low-dose dopamine on urine output and natriuresis in critically ill oliguric patients and the relationship of this response to the renin-angiotensin aldosterone system. DESIGN: A prospective, controlled study. SETTING: A multidisciplinary intensive care unit of a teaching hospital. SUBJECTS: Critically ill, volume-resuscitated, oliguric patients. INTERVENTION: Dopamine was infused at a rate of 2 micrograms/kg/min. The change in urine output and sodium excretion was measured over a 6-hour period. Plasma Renin Activity (PRA) and serum aldosterone were measured before commencing low dose dopamine. OUTCOME MEASURE: Patients whose mean urine output increased by greater than 20 ml/hour were considered to have responded to low-dose dopamine. RESULTS: Nine patients were studied. Five of the nine patients responded to low dose dopamine. The mean increase in urine volume was 58.4 ml/hr in the responders compared with 5.0 ml/hr in the nonresponders. The mean PRA (normal, 0.8 to 2.5 ng/ml/hr) was 5.7 ng/ml/hr in the responders compared with 26.8 ng/ml/hr in the nonresponders (p = 0.042). A significant inverse correlation existed between the PRA and the increase in urinary output (r = -0.75; p = 0.019). CONCLUSION: The response to renal dopamine in critically ill patients appears to be dependent on the interaction between the vasodilating-natriuretic effect of dopamine and the vasoconstricting antinatriuretic effect of the renin-angiotensin aldosterone system. PMID- 8449763 TI - Learning styles and teaching/learning strategy preferences: implications for educating nurses in critical care, the operating room, and infection control. AB - OBJECTIVE: To assess the learning styles and educational strategy preferences among critical care nurses, operating room nurses, and infection control practitioners. DESIGN: Descriptive multicenter survey using a self-report questionnaire. SETTING: 108 hospitals from nine geographic regions of the United States. PARTICIPANTS: A random sample of 303 (93%) nurses in the three specialties responded to the survey questionnaires. RESULTS: The majority of participants (64%) had an abstract learning style and preferred the self directed, discovery approach to learning. CONCLUSIONS: Nurses may be more abstract in their learning styles than previously reported. Experiential learning theory is an effective means of identifying nurses' learning styles and teaching/learning preferences, which can then be used to plan basic and continuing educational programs. PMID- 8449764 TI - Selected nosocomial viral infections. AB - A nosocomial viral infection is defined as a viral infection the onset of which occurs when the patient has been hospitalized longer than the incubation period of the virus. Viruses account for about 5% of all nosocomial infections. Viral cross-infection is most common in infants and children but also occurs in other groups, including the elderly, institutionalized persons of all ages, immunocompromised hosts, and patients with underlying chronic pulmonary, renal, or cardiac disease. These infections are associated with extended length of hospital stay and considerable morbidity and mortality. The spectrum of nosocomial viruses is wide and includes blood-borne, respiratory tract, and enteric pathogens, among others. This review will discuss the clinical characteristics, transmission, and control of the common nosocomial respiratory viruses: respiratory syncytial virus, varicella zoster virus, influenza virus, adenovirus, parainfluenza, and rubeola. PMID- 8449765 TI - Spotlight article: smoking cessation after acute myocardial infarction: effects of a nurse-managed intervention. (Taylor CB, Houston-Miller N, Killen JD, DeBusk RF. Ann Intern Med 1990; 113[2]: 118-23.). PMID- 8449766 TI - Accuracy of heart rate assessment in atrial fibrillation. PMID- 8449767 TI - Pulmonary artery pressure measurement: state of the art. AB - The measurement of pulmonary artery pressure is a highly complex skill. Numerous technical variables can affect the reliability and validity of hemodynamic measurements: zeroing, referencing and evaluating the dynamic response characteristics of the pressure system, expected pressure fluctuations, stabilization period, and the effects of position and ventilation. This article presents a review of the literature related to the technical aspects of pulmonary artery pressure measurement. Recommendations for practice are presented in a research-based protocol. PMID- 8449768 TI - Criminal law and the home healthcare nurse. PMID- 8449769 TI - Mrs. Valdez needs a home healthcare nurse. PMID- 8449770 TI - A coordinated approach to home infusion care. AB - Home intensive care can now be delivered in the patient's home. The growth of this clinical setting has been attributed to aging, an increase in technology, and national reimbursement patterns. Institutional nurses must anticipate and meet the patient's need for education and training specific to the therapeutic treatment to be provided at home, especially in the case of the acutely ill patient requiring home infusion therapy. Thus our technologically advanced system demands a coordinated approach. PMID- 8449771 TI - The role of prevention in home healthcare nursing practice. AB - Prevention is part of nursing practice, including home healthcare. Two National Health Objectives are highlighted: prevention of breast and cervical cancer. Skilled management, under Medicare, may be one way for home healthcare staff to focus on prevention and health promotion. PMID- 8449772 TI - Home care of the bone marrow transplant recipient: high tech, high touch. AB - Home care professionals are responsible for keeping abreast of the latest therapies used to treat specific disease entities to provide comprehensive and quality care. This article gives an overview of bone marrow transplantation, a complex treatment used for malignant and nonmalignant diseases. The transplant process, complications, and the role of home care for this population are discussed. PMID- 8449773 TI - Community nursing needs of newborns with myelomeningocele and their families. AB - The needs of newborns with myelomeningocele are a special challenge to the community health nurse. An in-depth knowledge of the pathophysiology of myelomeningocele, the ability to act as a communication channel between agencies, and the provision of ongoing advocacy, supportive counseling, and education to individual families and the community are necessary in addition to standard nursing care. Community health nurses provide this vital link in the holistic care of children with myelomeningocele and their families. PMID- 8449774 TI - Teamwork in home infusion therapy: the relationship between nursing and pharmacy. AB - To admit a client to a home infusion therapy program effectively and efficiently, all of the parties involved must take part in the planning process and decision making. The registered nurse and pharmacist are not the only players on the home healthcare team involved in planning for home infusion therapy, but their relationship is especially critical for a smooth transition to the home setting. Good communication between the nurse and pharmacist and a basic understanding of responsibilities are keys to successful coordination of care delivery. But communication can be challenging when the pharmacist and nurse do not work in the same physical location, which is often the case. PMID- 8449775 TI - 1993 special report. Moving healthcare into the 21st century. PMID- 8449776 TI - Hospice-assisted suicide. PMID- 8449777 TI - Wound care. PMID- 8449778 TI - Hospice care in a patient's residence. PMID- 8449779 TI - [Hearing disorders caused by myo-arthropathies of the temporomandibular joint]. PMID- 8449780 TI - [Modern lacrimal duct surgery produces functionally and cosmetically acceptable results]. PMID- 8449781 TI - [Laser Doppler vibrometry of the tympanic membrane. Possibilities for objective middle ear diagnosis]. AB - In the diagnosis of hearing disorders, the laser velocimeter can be used to advantage. In contrast to previously published studies on measurements at exposed middle and inner ear structures of the human temporal bone, we used a clinically more practical method to obtain results through the intact auditory meatus. We used a laser intensity of less than 1 mW. The measurements were performed in a room with unlimited sound transmission of frequencies between 0.5 and 8 kHz. The signals from the vibration of the tympanic membrane, obtained by this touch-free method, were analyzed by Fourier transform, showing only the fundamental oscillation but not the higher harmonics. Experimental data on middle ear effusions, obtained by fixation of the malleus head and by drilling the temporal bone, are presented. PMID- 8449782 TI - [Endonasal microsurgical treatment of lacrimal duct stenoses. Indications, technique and results]. AB - In a retrospective study we examined the indications, results and complications of endonasal microscopic dacryocystorhinostomy. Eighty-five operations were evaluated. Surgical success was proven in 83% for all indications using a combination of subjective judgement and objective findings. For the so-called classic indications--postsaccal stenosis, functional stenosis dacryolith and acute empyema--the operation was successful in 91% of cases. There were no permanent side effects. PMID- 8449783 TI - [A new method for diagnostic-therapeutic evaluation of rhinomanometry results]. AB - We have developed a new method for the clinical evaluation of nasal permeability by comparing flow (Vt) and subjectively estimated patency (D). In a coordinate system Vt is marked on the y-axis and D is recorded on the x-axis. The y-axis is separated into an operative and a non-operative part. The limit of Vt is 700 cm3/s. Four quadrants are produced, in which quadrant I is a conformity between the non-operative part of the flow and the value estimated by the patient (showing that no operative intervention is indicated). Conformity between the operative part and estimated value in quadrant III means that an operation is indicated. Discrepancies exist in quadrants II and IV and designate conservative therapy. Since clear directions for treatment are possible from each quadrant, the principle is easily programmable for use in a microprocessor, which is small and portable. PMID- 8449784 TI - [Results, complications and efficacy of micromediastinoscopy]. AB - In a retrospective study we examined all 72 patients who underwent a mediastinoscopy using the surgical microscope described by Meuser in 1968. A total of 74 operations was performed. In only 3 cases was there a false-negative result. Test sensitivity was 95%, specificity 100% and effectiveness 96%. Complications involved 2 cases of pneumothorax (for which no further therapy was necessary), 1 case of bleeding from a branch of the brachiocephalic trunk and 1 case of persistent lymphorrhagia with chylothorax, which was stopped by repeat mediastinoscopy. Preconditions for mediastinoscopy to minimize complications and false-negative results are: preoperative CT of the thorax, good cooperation with an anaesthesiologist, use of a microscopic and other special instruments and intraoperative frozen sections of tissue biopsies. PMID- 8449785 TI - [Chondrosarcoma of the nose and paranasal sinuses. Status of diagnostic imaging and therapeutic concept]. AB - Chondrosarcomas of the nose and paranasal sinuses are extremely rare. The present report deals with a case of chondrosarcoma situated in the ethmoid, destroying the cribriform lamina and infiltrating into the orbit. Diagnosis and therapy are discussed. The possibilities offered by imaging techniques and the advantages of magnetic resonance imaging are presented. PMID- 8449786 TI - [Polypoid pansinusitis in an unusual, extra-intestinal manifestation of Crohn disease]. AB - A 17-year-old female patient with known Crohn's disease developed a polypoid pansinusitis and a peritonsillitis during an acute inflammatory phase of her disease. The symptoms observed in the paranasal sinuses and in the oropharynx disappeared after treatment with cortisone and antibiotics was started. The histological findings in the biopsy specimens taken from the affected regions as well as the course of the disease suggest the extraintestinal manifestation of Crohn's disease. PMID- 8449787 TI - [Pharyngeal tuberculosis as a differential diagnosis to carcinoma]. AB - The differential diagnosis of pharyngeal tumors includes malignomas as well as chronic inflammatory processes. Squamous cell carcinoma is the most prevalent malignoma of the pharynx, representing about 90% of all malignomas of the head and neck. Malignant lymphomas, lymphoepithelial tumors (Schmincke's tumor) and anaplastic carcinomas are less prevalent. Amelanotic melanoma, rhabdomyosarcoma and extramedullary plasmocytoma are rare malignomas of the pharynx. Infectious diseases may also be a cause of pharyngeal tumors which have been reported to be associated with mycobacterial infections, syphilis, leproma, malleus and anthrax. Sarcoidosis and Wegener's granulomatosis are chronic inflammatory diseases of unknown etiology. We report a case of a 65-year-old female with an 11-year history of a slowly progressing tumor of the nasopharynx who had been admitted to hospital with suspicion of a malignoma. PMID- 8449788 TI - [Pseudoglottis after laryngeal trauma with bilateral recurrent laryngeal nerve paralysis]. AB - Voice is produced by a steady flow of air from the lungs, which is segmented at the laryngeal level into a series of air puffs. The segmentation is facilitated by periodic vocal fold vibrations under physiological conditions. In some cases, as in partial laryngectomy, segmentation of air stream is caused by vibrations of the false vocal folds. Here we report a case of an air stream segmentation mechanism at the laryngeal level producing an acceptable voice quality after fracture of the larynx and bilateral vocal fold paralysis. A lateral fixation of the left vocal fold was performed because of dyspnea. Six years later the patient was reexamined, at which time he had fairly intelligible speech and did not complain about dyspnea or aspiration. The voicing source was found to be a round soft tissue lump of approximately 1.5 cm diameter. This tissue was formed from the former left arytenoid area. During phonation the right arytenoid cartilage approximated to the petiolus, while the left neoarytenoid closed the residual opening of the larynx. However, during voicing, this latter tissue exhibited a vertical vibratory pattern similar to false vocal fold vibration and mucosal vibration of true vocal folds at high pitch. It seems reasonable to speculate that the mass of the tissue lump had become well balanced so that the very low pitch of the false vocal fold and a high pitch as in head register phonation could be avoided. Since the patient suffered from a pronounced gag reflex during examination, stroboscopy was videorecorded and analyzed off-line.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8449789 TI - [Correlation between inner ear disorders and temporomandibular joint diseases]. AB - Acute and chronic inner ear diseases involve many etiological factors, some as yet unknown. ENT-specific, orthopedic, hemorrheological, immunological and neurological disorders can affect the cochleovestibular system and induce hearing loss, vertigo and/ortinnitus. We performed a prospective study to analyze factors of the dentognathological system and of the temporomandibular joint that can influence acute and chronic inner ear dysfunctions. A total of 138 patients (49.3% female, 50.9% male) receiving clinical treatment for inner ear dysfunctions (12.3% chronic sensorineural hearing loss, 15.2% Meniere's disease, 52.2% sudden hearing loss, 13.8% isolated tinnitus, 6.5% recurrent hearing loss) underwent a prospective dental and gnathological examination. In particular, the patient's dental status and a functional investigation of the masticatory muscles and the temporomandibular joint were analyzed. In 20.3% patients the examination showed no pathology of the dentognathological system. In contrast, there were pathological findings in 110 patients (79.7%): in 43.5% a temporomandibular joint syndrome was diagnosed, in 29% parafunction of the occlusion, and in 35% a myopathy of the masticatory muscles. Additionally 32.6% patients showed dental disorders that required treatment; 11.65% had problems with dentures and 20.3% malpositioned wisdom teeth. In 16 patients the recommended dental treatment was followed up and improvement of otological symptoms was found in 56.6%. The present investigation shows that many patients with inner ear dysfunction suffer from dentognathological disorders. For a subgroup of patients there exists the possibility of improving otological symptoms by dental treatment. Therefore we recommend a dentognathological examination in patients with inner ear dysfunctions of unknown etiology. PMID- 8449790 TI - Concerned about material safety data sheets. PMID- 8449791 TI - More comments on Council Report. PMID- 8449792 TI - Marine Mammal Center an unusual workshop. PMID- 8449793 TI - Macfie continues in mountain gorilla conservation. PMID- 8449795 TI - 1991 professional incomes of US veterinarians by years since graduation. PMID- 8449794 TI - Reminder to veterinarians: observe OSHA requirements. PMID- 8449796 TI - The art of leadership. PMID- 8449797 TI - Economic analysis of a mastitis monitoring and control program in four dairy herds. AB - Mastitis monitoring and control programs were instituted in 4 Illinois dairy herds for 12 months. Two herds had high mean monthly bulk tank somatic cell counts (> 490,000 cells/ml) and 2 had low mean monthly bulk tank somatic cell counts (< 260,000 cells/ml) at the start of the study. The mastitis monitoring and control programs included mandatory mastitis control measures, as well as individualized control measures that were based on results of bacterial cultures of milk, bulk tank milk analyses, milking machine and milking procedure evaluations, and environmental inspections in each herd. Changes in mastitis prevalence, clinical mastitis incidence, milk yield, and individual cow somatic cell counts were evaluated, and an economic analysis was performed for each herd. Mastitis-associated economic losses during the study period ranged from $161.79 to $344.16/lactating cow in the 4 herds. Gross economic benefits resulted when mastitis-associated losses were lower with the monitoring and control program than predicted without it. There were no gross economic benefits in the herds with low somatic cell counts, and, when the marginal costs of the programs were added, there were large net losses ($84.06 and $113.01/lactating cow) in those herds. Gross economic benefits resulted in both of the herds with high somatic cell counts. However, in 1 of the herds, the marginal costs of the program exceeded the benefits, resulting in a net loss of $12.96/lactating cow. The net loss was attributed primarily to poor producer compliance with recommendations. There was a net economic benefit of $19.11/lactating cow in the other herd with high somatic cell counts, in which producer compliance was better.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8449798 TI - Prevalence of contagious pathogens of bovine mastitis and use of mastitis control practices. AB - A cross-sectional study of 1,032 dairy herds in Ohio was conducted to determine the prevalence of the major contagious pathogens of mastitis (Streptococcus agalactiae and Staphylococcus aureus) and the use of common mastitis control measures. Herd owners were surveyed by mail concerning their use of mastitis control measures. The survey focused on treatment of nonlactating cows, postmilking teat dipping, culling practices, milking machine maintenance, treatment for clinical mastitis, and premilking hygiene practices. Nearly 90% of questionnaires were returned. The prevalence of Streptococcus agalactiae and Staphylococcus aureus was determined by use of bulk-tank milk samples. Most herds (n = 802) met the criteria for classification into 1 of 4 groups: (1) Free of contagious pathogens, as determined by inability to isolate coagulase positive staphylococci (CPS) and esculin-negative CAMP positive streptococci (ENCPS) from 3 bulk-tank milk samples, (2) CPS, but not ENCPS, isolated from at least 1 sample, (3) ENCPS, but not CPS, isolated from at least 1 sample, (4) both ENCPS and CPS isolated from at least 1 sample. The number of herds in which both ENCPS and CPS were isolated was low; therefore, these herds were grouped with herds in which ENCPS alone was isolated for the evaluation of mastitis control practices related to herd pathogen status. Herd somatic cell count (SCC) was determined using Dairy Herd Improvement Association data by calculating the geometric mean SCC from individual cow test day SCC. Twelve months of SCC data from 741 herds were included in this study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8449799 TI - Lungworm infection in a sheep flock in Maryland. AB - First-stage larvae of Protostrongylus rufescens were detected in the feces of a ram with diarrhea, anorexia, weight loss, and mucopurulent nasal discharge. Subsequently, a survey was initiated in the experimental sheep flocks maintained at the Agricultural Research Service's Helminthic Diseases Laboratory in Beltsville, Md to determine the extent and effect of infection with the parasite. Five of 31 ewes and 4 of 16 rams were found to be infected with the lungworm. Clinical signs of infection, which ranged from mild to severe, included diarrhea, weight loss, and respiratory distress. Natural transmission of the parasite to parasite-naive lambs grazing on pasture occurred during the course of this study. Three lambs born to infected ewes during this study were not infected, suggesting that there is no vertical transmission. Additionally, cattle grazing the same pastures as infected sheep were not infected with the parasite. Results of this study indicated that Protostrongylus rufescens can cause serious disease in domestic sheep in the United States and should be considered as a differential diagnosis in sheep with nonspecific respiratory tract signs. PMID- 8449800 TI - Effects of oral administration of a calcium-containing gel on serum calcium concentration in postparturient dairy cows. AB - Various nutritious nutritional-supplement gels are being marketed for use in veterinary medicine. This study was designed to determine whether serum calcium, phosphorous, or magnesium concentrations were different between cows given a gel containing calcium chloride as its active ingredient (treated) and cows given inert carrier gel (control). The study revealed a significant (P < 0.01) increase in serum total calcium concentration within 5 minutes of administration of a calcium gel given to cows within 1 hour of parturition. Serum total calcium concentration had returned to baseline value by 24 hours after calcium gel administration. Serum inorganic phosphorus concentration also increased significantly (P < 0.05) after treatment. Significant changes in serum magnesium concentrations were not detected. PMID- 8449801 TI - Use of an on-farm progesterone test in the clinical management of parturient disorders in three cows. AB - Measurement of blood progesterone concentrations with a rapid, on-farm test was used to guide the clinical management of 3 cows with parturient disorders. An 8 year-old cow in the third trimester of pregnancy had chronic vaginocervical prolapse with partially dilated (4 cm) necrotic cervix. Blood progesterone concentration estimated with the test kit was low (< 2 ng/ml), and the cervical dilatation was attributed to stage-1 parturition. Vaginal delivery of the calf occurred 7 hours later. A 2-year-old cow examined for dystocia had a uterine torsion. Eighteen hours after apparent correction of the torsion, the cervix had failed to dilate. Blood progesterone concentration was 2 to 5 ng/ml, suggesting parturition had not yet been initiated. Parturition was induced with dexamethasone and prostaglandin, and calving occurred 32 hours later. A pregnant, 16-month-old heifer was believed to be about to calve and was admitted because of potential need cesarean section. Examination revealed the cervix to be closed. Blood progesterone concentration was low, and calving was predicted to occur within 24 hours. The heifer was monitored, and stage-2 labor was observed 8 hours later. The calf was delivered with minor assistance. In each case, the test provided diagnostic information that was useful in making therapeutic management decisions. PMID- 8449802 TI - Lynxacarus radovskyi infestation in a cat. AB - An adult domestic short-hair cat from south Texas was examined because of excessive dandruff on the back, neck, thorax, and hind limbs. Removal of a few hairs for microscopic evaluation revealed Lynxacarus radovskyi, the cat fur mite. The small (< 0.5 mm) mite could be readily identified by its laterally compressed body and its characteristic grasping of the hair shaft between the gnathosoma and palpi. Thus far, this mite has been identified as a parasite of cats in warm, humid environments. The number of parasites and apparent discomfort in cats varies considerably, from massive infestation with little discomfort to few mites and marked pruritus. Acaricides that are effective against other ectoparasites of cats apparently are effective in controlling L. radovskyi. PMID- 8449803 TI - Squamous cell carcinoma associated with a chronic wound in a horse. AB - A 13-year-old Belgian stallion developed a squamous cell carcinoma at the site of a neck laceration that had been treated topically with various irritating chemicals for 18 months. Orthovoltage treatments at 3 times over 5 years controlled the tumor. Eight years after the initial hospitalization, the area was healed and the stallion appeared healthy. PMID- 8449804 TI - Use of esophagoscopy in the diagnosis of esophageal squamous cell carcinoma in a horse. AB - Esophagoscopy allowed visualization and biopsy of a lesion within a diverticulum of the esophagus in an adult horse. Although the biopsy specimen obtained was small, diagnosis of squamous cell carcinoma was possible from histologic examination of the esophageal tissue sample retrieved by use of endoscopy. PMID- 8449805 TI - A 14/20 chromosome translocationp in Simmental cattle. AB - A 14/20 translocation was identified in 2 herds of Simmental cattle in the United States. All of the animals that carried the translocation had a common sire that was identified subsequently to carry the translocation. The semen of the bull had been used to inseminate a vast number of cows, so a substantial number of Simmental cattle in the United States may carry the 14/20 translocation. This translocation could have a detrimental effect on fertility in carrier animals; however, there are insufficient data about this particular abnormality to form conclusions. There appears to be sufficient evidence to urge caution in selecting carriers for breeding stock, especially when the potential exists for widespread dissemination of the abnormality through the use of artificial insemination. PMID- 8449806 TI - Generalized medullary infarction of the long bones in a horse. AB - Generalized medullary infarction of the long bones was diagnosed in a 12-year-old Tennessee Walking Horse mare. The mare was referred after a 6-week course of shifting weight on her hind limbs, and kicking. Physical examination revealed mild stifle joint distention and withdrawal reactions to digital pressure over the long bones. Radiography revealed patchy areas of medullary sclerosis in the distal portion of each femur and proximal portion of each tibia. A full-thickness cortical and cancellous tibial biopsy revealed infarcted bone marrow, with cortical and periosteal osteonecrosis. The cause of the intramedullary infarction could not be determined, but might have been attributable to cumulative bone stress resulting from mild primary hyperparathyroidism and some unidentified inflammatory factor. PMID- 8449807 TI - Use of iohexol as a gastrointestinal contrast agent in three dogs, five cats, and one bird. AB - Barium sulfate suspension is routinely used as contrast medium for upper gastrointestinal procedures. It has been contraindicated for use in cases of suspected perforation. In such instances, water-soluble iodides are recommended for use. Most of the water-soluble iodides available for use in veterinary medicine at this time are hyperosmolar. This results in in transit dilution of the contrast column. The dilution of the contrast agent within the intestines may prevent visualization of a perforation, especially if the perforation is in the distal portion of the small intestine. Iohexol a nonionic water-soluble iodide of low osmolality, is currently used in veterinary medicine for myelography. We have used it as the contrast agent for upper gastrointestinal studies in cases of suspected obstruction or perforation, with good results, and no adverse effects have been associated with its use. Opacity of the contrast column was adequate, and segmentation or flocculation of the column was not apparent. PMID- 8449808 TI - Increased alanine transaminase activity associated with tetracycline administration in a cat. AB - Administration of tetracycline was believed to be associated with an adverse drug reaction in a cat. Clinical signs consisted of anorexia, ptyalism, and signs of depression. The most noticeable biochemical abnormality was a markedly high serum alanine transaminase activity. Treatment consisted of vitamin E and selenium injections and feeding via a gastrostomy tube. Abnormalities noticed on histologic examination of hepatic tissue were centrilobular fibrosis, mild diffuse cholangiohepatitis, and mild hepatic lipidosis. The lipidosis was believed to have resulted from tetracycline administration, whereas the more chronic lesions (hepatic fibrosis and mild cholangiohepatitis) were believed to have resulted from preexisting, subclinical hepatic disease. Because serum alanine transaminase activity returned to reference ranges and the anorexia and ptyalism resolved with cessation of tetracycline administration, these abnormalities were believed to have represented an adverse drug reaction. Treatment of the cat with vitamin E and selenium was instituted on the basis of reported preventive and therapeutic effects in albino rats with tetracycline induced hepatic lesions. Whether these compounds had any role in accelerating clinical recovery in this cat is uncertain. PMID- 8449809 TI - Ruptured urinary bladder after dystocia in a cow. AB - Rupture of the urinary bladder of a cow occurred secondary to prolonged dystocia. Primary surgical closure of the tear was performed after drainage of the uroperitoneum, and the cow recovered without complications. PMID- 8449810 TI - Lesions of the caudal aspect of the femoral condyles in foals: 20 cases (1980 1990). AB - Medical records and radiographs were reviewed from 20 foals with caudal femoral condylar lesions. Osseous lesions were classified radiographically into 3 categories. Type-I lesions were characterized by a discrete area of radiolucency within the subchondral bone of the caudal aspect of a femoral condyle and were associated with septic arthritis and osteomyelitis. Type-II lesions had localized, osseous irregularities involving < 50% of the femoral condyle. Type III lesions had widespread irregularities involving a large area of the condyle, and in 5 foals with type-III lesions, there was a thin osseous fragment displaced from the condyle and free in the femorotibial joint pouch. Foals with type-I and III lesions were severely lame and often required assistance to stand. Foals with type-II lesions were not as lame, but lameness was evident at the trot and was exacerbated by flexion of the affected stifle. Cytologic evaluation of the synovial fluid from foals with type-I lesions was compatible with septic arthritis, whereas synovial fluid from foals with type-II and -III lesions was not septic. Surgical exploration and debridement were performed in 4 foals. Two foals with type-II lesions are currently performing athletically. The remaining 2 foals, in which surgery was performed, had type-III lesions; both of those foals were euthanatized at surgery because of the severity of the lesions. Follow-up information was available in 5 foals that did not have surgery. Two foals with type-I lesions and 1 foal with a type-III lesion were sound 1 year after diagnosis. One foal with a type-II lesion had residual lameness that prevented performance, and 1 foal with a type-III lesion was salvaged for breeding. Eleven foals were euthanatized and available for postmortem examination. Gross examination of the joints in foals with type-I lesions revealed a subchondral bone defect with intact articular cartilage in 3 of 4 foals examined. In 1 foal with a type-II lesion, a gross examination was performed, which revealed a focal indentation of the articular cartilage and on cross section had a retained cartilaginous core. Postmortem examination of 4 foals with type-III lesions revealed a large, denuded area with a shell-like cartilage fragment free within the joint. Two additional foals within this same group had marked irregularity of the articular cartilage with deep reticulation in the articular surface. In 2 of 3 foals examined with type-I lesions, histologic examination revealed suppurative osteomyelitis. The third foal in this group had changes compatible with focal ischemia.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8449811 TI - Adenomatous polyps of the duodenum in cats: 18 cases (1985-1990). AB - Medical records were reviewed for 18 cats with adenomatous polyps of the proximal portion of the duodenum. Cats of Asian ancestry were over represented (8/18), and male castrated cats were common (15/18). The median age was 11.8 years. Common clinical signs were acute and chronic vomiting and hematemesis. Nine cats were anemic. Contrast radiography was performed in 12 cats, and a mass of the proximal portion of the duodenum was identified in 10 cats. Endoscopy was used to confirm existence of the mass in 3 cats. Complete excision of the duodenal mass was performed in 17 cats. One cat died before abdominal exploratory surgery, and a duodenal adenomatous polyp was identified at necropsy. Fifteen cats survived the immediate postoperative period, with 13 of 15 having complete resolution of clinical signs. Five cats had concurrent disease, which caused 4 of them to die between 3 and 26 months after surgery. Redevelopment of adenomatous polyps was not detected in any cat during the follow-up period of 1 to 49 months. Results of the study indicated that benign, adenomatous polyps of the duodenum in cats can be safely excised and that the prognosis for return to normal function is excellent. PMID- 8449812 TI - What is your diagnosis? Severe generalized pulmonary edema. PMID- 8449813 TI - What is your diagnosis? Poor intra- and retroperitoneal contrast suggestive of emaciation and alimentary visceral displacement consistent with bladder or uterine mass. PMID- 8449814 TI - The status of data on minority practitioners in selected allied health professions. PMID- 8449815 TI - Advances in educational technology--IVD, CD-I, and journeys into virtual reality. PMID- 8449816 TI - Assessing the feasibility of continuing an allied health educational program: a strategic planning model. AB - Some allied health programs consume more resources than they generate. Decision makers are often required to evaluate the need for continuing such programs. This paper presents a methodology for analysis of programs that do not cover their costs with the revenue that they generate. Although the subject presented is a clinical laboratory science program, the methodology and the examples provide a model and instruction on how to conduct a similar analysis for any allied health program, and a summary of the types of conclusions such an analysis might afford. PMID- 8449817 TI - A survey of high school seniors' career choices: implications for allied health. AB - This paper describes a research study conducted using a survey instrument to determine what factors influence high school seniors when making decisions related to future careers and college education. Students were asked to indicate what careers they intended to pursue, what people and factors influenced their careers choices, and their familiarity with and impressions of the allied health professions. The majority indicated that personal satisfaction, employment opportunities, and income were the most important factors influencing their career choices. Although 76.5% of the respondents had a favorable impression of allied health, only 15% indicated that they were very familiar with the allied health professions. The results here and in other studies point to lack of knowledge rather than lack of interest as the leading cause of enrollment vacancies in allied health curricula. PMID- 8449818 TI - Medical technologists' perceptions of their work: results of perception of work study in Sweden. AB - The subjective perceptions of autonomy, occupational hazards, job satisfaction, and work content were studied for a sample of medical technologists (MTs) employed in clinical chemistry in Sweden. The sample (N = 488) consisted of a randomized tenth of the members of the MT trade union. A mailed questionnaire was completed by 359 (73.6%) MTs. A further validation was performed through interviewing 48 MTs who had not participated in the survey. The answers in the validation study corresponded well to the distributions of the answers in the main study. The MTs' job satisfaction was high, which is in accordance with a European survey, but contradictory to American studies. However, the overall picture of the MTs' perception of their work in the present study was contradictory: an ideal of what they want the occupation to be, and a reflection of a reality that partly causes considerable dissatisfaction. This may suggest that medical technology is undergoing a process of professionalization. PMID- 8449819 TI - The Tomizo Yoshida Prize. PMID- 8449820 TI - Southernmost carriers of HTLV-I/II in the world. AB - To clarify the real distribution of HTLV-I and -II carriers among indigenous people in central and South America, blood samples collected from indigenous people in isolated regions of Southern Chile were examined. Among 199 inhabitants from Chiloe Island and Pitrufquen town, three cases (1.5%) showed positive anti HTLV-I antibodies. Two out of the three (82-year-old male and 58-year-old female) reacted to HTLV-II-specific Gag and/or Env proteins but not to HTLV-I-specific ones. The latter case was confirmed as an HTLV-II carrier by polymerase chain reaction test. PMID- 8449821 TI - Relationship of diet to small and large adenomas of the sigmoid colon. AB - The relation of dietary factors to the risk of adenomas of the sigmoid colon was examined in men receiving a retirement health examination at the Self-Defense Forces Fukuoka Hospital between October 1986 and 1990. A total of 187 adenoma cases and 1557 controls with normal colonoscopy were identified in the series. Cases were further classified into small-adenoma (< 5 mm, n = 78) and large adenoma (> or = 5 mm, n = 67) groups. The consumptions of selected foods and beverages were ascertained before colonoscopy by means of a self-administered questionnaire. After adjustment for smoking, alcohol use, rank and body mass index, low rice consumption and high meat intake were independently associated with an increased risk of large adenomas. The risk of small adenomas was not related to either rice consumption or meat intake. Adjusted odds ratios of large adenomas for the low, intermediate and high consumption levels of rice were estimated to be 1.0 (referent), 0.83 and 0.43, respectively (trend P = 0.08), and the corresponding figures for meat consumption were 1.0 (referent), 1.58 and 2.38, respectively (trend P = 0.02). The findings suggest that low rice consumption and high meat intake may promote the growth of colon adenomas, thereby increasing the risk of colon cancer. PMID- 8449822 TI - Sequential observation of rat prostate lesion development induced by 3,2' dimethyl-4-aminobiphenyl and testosterone. AB - 3,2'-Dimethyl-4-aminobiphenyl (DMAB), when combined with high doses of testosterone propionate (TP) induces invasive adenocarcinomas with metastatic potential in the rat prostate. The processes underlying this tumor development, including the involvement of atypical hyperplasias, were sequentially investigated in F344 rats. DMAB was given subcutaneously at a dose of 50 mg/kg body weight 10 times at 2-week intervals. TP was administered chronically (in Silastic tubes) from the beginning of the experiment or after the DMAB administration until termination (week 60). Invasive adenocarcinomas were induced in the lateral and anterior prostate as well as the seminal vesicles. Atypical hyperplasias appeared from an early stage, with the later appearance of cancers being closely associated with such foci of morphological alteration. The findings confirm that combined administration of DMAB and pharmacological doses of TP yields invasive adenocarcinomas in the rat prostate and provide further support for the conclusion that atypical hyperplasias are premalignant lesions. PMID- 8449823 TI - Effects of X-irradiation on N-methyl-N-nitrosourea-induced multi-organ carcinogenesis in rats. AB - The effects of X-irradiation on N-methyl-N-nitrosourea (MNU)-induced multi-organ carcinogenesis were examined in both sexes of ACI/N rats. At 6 weeks of age, rats in groups 1 (25 males, 25 females) and 3 (24 males, 23 females) received a single i.p. injection of MNU (25 mg/kg body weight), while those in groups 2 (25 males, 26 females) and 4 (25 males, 25 females) were administered the carcinogen at a dose of 50 mg/kg body weight. At 10 weeks of age, groups 3 and 4 were X irradiated at a dose of 3 Gy. Group 5 (24 males, 24 females) received X irradiation alone. Group 6 (21 males, 21 females) served as an untreated control. As a result, neoplasms developed mainly in the digestive tract, kidney, uterus, and hematopoietic organ in groups 1-5. The incidences of adenocarcinoma in small and large intestines of male rats of group 4 (50 mg/kg MNU and X-irradiation) (small intestine: 48%, large intestine: 32%) were significantly higher than those of group 2 (50 mg/kg MNU) (small intestine: 17%, P < 0.05; large intestine: 8%, P < 0.05), and also the frequency of adenocarcinoma in the large intestine of males of group 3 (25 mg/kg MNU and X-irradiation) (22%) was significantly greater than that of group 1 (25 mg/kg MNU) (0%, P < 0.05). These results indicated that X irradiation enhanced the development of intestinal neoplasms induced by MNU in male ACI/N rats. PMID- 8449824 TI - Effect of an inhibitor of tumor promotion, alpha-Difluoromethylornithine, on tumor induction by repeated beta irradiation in mice. AB - alpha-Difluoromethylornithine (DFMO) is an inhibitor of putrescine biosynthesis and of tumor promotion. Studies were made of its effect on induction of skin and bone tumors by repeated beta irradiation of the back of female ICR mice 3 times weekly at a dose of 3 Gy per exposure. When given at a concentration of 10 mg/ml in the drinking water, DFMO significantly delayed the time of tumor emergence and decreased the yield of skin tumors, although the cumulative tumor incidence computed by the Kaplan-Meier method finally reached 100%. These results indicate that tumor-promoting activity is involved in repeated beta irradiation, besides its tumor-initiating activity. PMID- 8449825 TI - bcl-2 gene rearrangement analysis of Japanese follicular lymphomas by polymerase chain reaction in formalin-fixed, paraffin-embedded tissue specimens. AB - The prevalence of chromosomal translocation t(14;18) was examined in 41 cases of follicular lymphoma covering all histopathological subtypes, using the polymerase chain reaction and hybridization method with non-radioactive oligonucleotide probes. DNAs were extracted from unfixed fresh-frozen and/or formalin-fixed paraffin-embedded biopsy specimens. The t(14;18) chromosomal translocation, resulting in bcl-2-JH (immunoglobulin heavy chain gene joining segment) fusion gene, was detected in 7 (36.8%) of 19 follicular small cleaved cell lymphomas and 6 (54.5%) of 11 follicular mixed, small cleaved cell and large cell lymphomas. Meanwhile, 11 cases of follicular large cell lymphoma revealed no bcl-2-JH fusion gene. There was a statistically significant difference in the frequency of bcl-2 JH rearrangement between follicular, small cleaved cell and large cell lymphoma (two-sided Fisher exact test, P = 0.049). The difference of bcl-2 rearrangement frequency between follicular, mixed and large cell lymphoma was also statistically significant (P = 0.012). PMID- 8449826 TI - Aberrant expression of the p53 tumor suppressor gene in adult T-cell leukemia and HTLV-I-infected cells. AB - By immunoprecipitation analysis, enhanced p53 expression was detected in 3 of 4 adult T-cell leukemia (ATL) cell lines, 1 of 3 HTLV-I-infected cell lines and 1 of 5 fresh ATL samples, compared with phytohemagglutinin-stimulated peripheral blood lymphocytes. Among these 5 high expressers, p53 missense mutations were indicated in 2 ATL cell lines and 1 fresh ATL sample by extensive p53 cDNA and genomic DNA polymerase chain reaction single-strand conformation polymorphism analysis. No mutation was found throughout the entire coding region of the remaining 2 high expressers (1 ATL and 1 HTLV-I-infected cell lines) and low expressers of p53 (2 HTLV-I-infected cell lines). Tax oncoprotein expression was found in these 2 high p53 expressers in which p53 mutation was not present, but not in low p53 expressers or cells carrying this mutation. The levels of p53 mRNA were similar among the samples regardless of p53 levels. Posttranscriptional mechanisms other than missense mutation would thus appear to increase p53 in the Tax-expressing cells but not in cells containing undetectable levels of Tax. No complex formation between p53 and Tax was observed. PMID- 8449827 TI - Random process of metastasis and generation of heterogeneity in a mouse sarcoma line. AB - The process of metastasis was analyzed in 505-05-01 cells, an established line of a methyl-cholanthrene-induced mouse sarcoma, by tagging the cells with the pSV2neo plasmid. A dominant clone was identified which, upon transplantation together with other clones, overgrew tumors in the kidney capsule. However, when this clone was transplanted in a mouse collaterally with recessive clones, both clones grew at the same rate and metastasized to the lung at an equal frequency. This suggests that the process of metastasis in this particular sarcoma line is stochastic, the dominant population having a better chance to colonize to the lung. The dominant neomycin-resistant clone was transfected with another marker plasmid, pY3, which confers resistance to hygromycin. Results of mixed inoculation of 9 independently isolated clones revealed the hierarchy of dominance among clones. This indicated the existence of heterogeneity within the parental clone. Upon mixed inoculation with hygromycin-resistant clones, the parental clone overgrew in the tumors. This indicated that some clone had changed its phenotype to become less aggressive. Thus, the direction of phenotypic drift in vitro seems to be random in terms of behavior in vivo. PMID- 8449828 TI - Artificial pneumothorax as a risk factor for development of pleural lymphoma. AB - An etiologically important role of chronic tuberculous empyema for development of pleural lymphocytic lymphoma of B-cell type has been suggested. To examine risk factors for development of pleural lymphoma in patients with chronic tuberculous empyema, a case-control study was carried out. Onset age of lung tuberculosis and empyema, presence of chemotherapy, surgical treatment, extent of empyema, presence of fistula, history of smoking, and height and weight of patients at first admission were compared in patients with empyema alone (70 controls) and empyema complicated with lymphoma (42 cases): the date of birth and sex were matched by group. The patients receiving artificial pneumothorax showed a significant increase in risk for development of pleural lymphoma (relative risk = 4.92, P < 0.05). We could not find any report describing development of pleural neoplasias in patients with chronic empyema receiving surgical resection of pleural pyogenic membrane. From these findings, it is suggested that artificial pneumothorax left chronic non-healing inflammation in the pleural cavity, which resulted in development of pleural lymphoma. PMID- 8449829 TI - Characterization of OM-B monoclonal antibody-defined antigen associated with mucinous type human ovarian tumor. AB - Partial characterization of the OM-B antigen associated with mucinous-type ovarian tumors was conducted. This antigen was defined by OM-B monoclonal antibody, which was raised against a mucinous-type ovarian tumor, and was present in all the mucinous-type tumors tested, but only a fraction of serous-type tumors. The OM-B crude antigen preparation fractionated from cystic fluids had a density of 1.40-1.43 g/ml, with a high neutral sugar content. Molecular mass (M(r)) estimated by gel filtration was more than 2,000,000. Trypsinization of the antigen preparation under appropriate conditions resulted in two major bands and one minor band with molecular sizes of less than M(r) 250,000, as detected by immunoblotting. Immunoaffinity chromatography was then conducted and the amino acid composition of the purified product was determined; the high contents of serine, threonine and proline are characteristic of a mucin. Binding inhibition enzyme-linked immunosorbent assay was developed to measure OM-B antigen activity in cystic fluids and sera from patients with mucinous-type tumors. The antigen was easily detected in most cystic fluids, but not in sera, suggesting that improvement in the sensitivity of this assay is necessary before its utilization for serum diagnosis will be feasible. PMID- 8449830 TI - A cancer-reactive human monoclonal antibody derived from a colonic cancer patient treated with local immunotherapy. AB - A human monoclonal antibody, YJ-37 (IgM) was generated through the fusion of human B lymphoblastoid cell line HO-323 with the regional lymph node lymphocytes from a colonic cancer patient who was treated with a local immunotherapy. This antibody was purified and conjugated with biotin, after which direct immunohistochemical staining was performed. The results revealed that YJ-37 selectively reacted with colonic cancer (7/19), gastric cancer (3/6), endometrial cancer (1/2) and colonic adenoma (7/13), but not with normal epithelia. Membrane immunofluorescence and FACS analysis also showed that YJ-37 bound to tumor cell surfaces. Furthermore, the chemical structure of the antigen defined by YJ-37 was analyzed by means of thin-layer chromatography immunostaining and ELISA. The results indicated that YJ-37 reacted with sialylated lacto-series carbohydrate chains, which have been reported to accumulate in cancer cells. PMID- 8449831 TI - Differential alterations of dihydrofolate reductase gene in human leukemia cell lines made resistant to various folate analogues. AB - In order to clarify a molecular mechanism of folate resistance in leukemia cells, we studied alterations of the dihydrofolate reductase (DHFR) gene in a human leukemia cell line, MOLT-3, and its sublines made resistant to methotrexate (MTX), trimetrexate (TMQ) and N10-propargyl-5,8-dideazafolic acid (CB3717), alone or in combination. Major alterations of the DHFR gene were examined by Southern analysis of high-molecular-weight DNA. The presence of a base change (T-->C) at nucleotide position 91 of the DHFR gene, which is reported to be responsible for the reduced affinity of the enzyme for MTX in an MTX-resistant human colon carcinoma cell, was examined by allele-specific oligonucleotide hybridization. In a 10,000-fold MTX-resistant subline (MOLT-3/MTX10,000), the normal allele of DHFR gene had been amplified. In contrast, a 200-fold TMQ-resistant subline (MOLT 3/TMQ200) and a 30-fold CB3717-resistant subline selected from MOLT-3/TMQ200 (MOLT-3/TMQ200-CB-3717(30)) were shown to have the mutant allele. Furthermore, the mutant allele had been amplified in a 500-fold MTX-resistant subline, which was established by the continuous exposure of the MOLT-3/TMQ200 cells to stepwise increases of drug concentration and designated as MOLT-3/TMQ200-MTX500. On the other hand, a 40-fold-resistant subline to CB3717 alone (MOLT-3/CB3717(40)) showed the normal allele without amplification. These data suggest that complex alterations of the DHFR gene are involved in the molecular mechanisms of folate resistance that can be differentially introduced into leukemia cells by exposure to various folate analogues, alone or in combination. PMID- 8449832 TI - Analysis of DNA fragmentation in human uterine cervix carcinoma HeLa S3 cells treated with duocarmycins or other antitumor agents by pulse field gel electrophoresis. AB - Pulse field gel electrophoresis using a contour-clamped homogeneous electric field was applied for the analysis of DNA-fragmenting activity of antitumor agents towards human uterine cervix carcinoma HeLa S3 cells. Duocarmycins (DUMs), novel antitumor antibiotics with ultrapotent cell growth-inhibitory activities, caused DNA fragmentation at 10 times their IC50 values at 2 h exposure. At 100 times their IC50 values, the size of the smallest fragments was about 245 kilobase pairs (kbp). DUMA, DUMB1 and DUMB2 exhibited similar DNA fragmentation patterns, suggesting similar action mechanisms. DNA fragmentation was also detected in cells treated with radical producers, intercalators and topoisomerase inhibitors. Two bands of about 1800 and 1500 kbp were commonly detected in the cells treated with DUMs and these agents. In addition, fragments of about 900 kbp were detected in the cells treated with a topoisomerase inhibitor, 4'-(9 acridinylamino)methane-sulfon-m-anisidine, and fragments in the broad size range between 700 and 245 kbp in the cells treated with radical producers, bleomycin and neocarzinostatin. DUMs showed a characteristic DNA fragmentation pattern, since both types of fragments induced by the topoisomerase inhibitor and the radical producers were simultaneously detected, suggesting a novel mode of interaction with DNA. DNA-crosslinking agents and mitotic inhibitors did not induce DNA fragmentation under these conditions. The pulse field gel electrophoresis is potentially useful for characterizing DNA-cleaving activity of various antitumor agents at the cellular level. PMID- 8449833 TI - Antitumor activity of oenothein B, a unique macrocyclic ellagitannin. AB - The antitumor effect of oenothein B, a macrocyclic ellagitannin from Oenothera erythrosepala Bordas, on rodent tumors was studied. Oenothein B exhibited a strong antitumor activity against MM2 ascites tumors upon intraperitoneal administration to the mice before or after the tumor inoculation. The tannin also inhibited the growth of Meth-A solid type tumor in mice. This antitumor effect of the tannin could not be attributed to its direct cytotoxic action on tumor cells, because the cytotoxicity was very weak in the presence of serum protein. When oenothein B was injected into the peritoneal cavity of mice, peritoneal exudate cells, including cytostatic macrophages, were induced. Furthermore, in the in vitro treatment of macrophages from mice and humans, the tannin stimulated release of an interleukin 1 (IL-1)-like activity and IL-1 beta from the cells. These results suggest that oenothein B exerts its antitumor effect through potentiation of the host-immune defense via activation of macrophages. PMID- 8449834 TI - Meeting the challenges of beta-lactamases. AB - A wide variety of beta-lactamases are found in clinical isolates of bacteria and, when present, these enzymes often result in resistance to one or more beta-lactam antibiotics. The prevalence of organisms with these enzymes has increased as beta lactams have been increasingly used in clinical practice. This paper defines the nature of these enzymes and details the attempts to overcome the problem of resistance mediated by beta-lactamase, efforts which have culminated in the development of a series of effective beta-lactamase inhibitors which can be combined with beta-lactam antibiotics. The currently available compounds, clavulanic acid, sulbactam, and tazobactam are very effective inhibitors of many types of beta-lactamases, but there are additional enzymes which are resistant even to these inhibitors and which pose continuing challenges for the pharmaceutical chemist and clinician alike. PMID- 8449835 TI - Treatment of intra-abdominal infections. AB - Intra-abdominal infections are caused by a mixture of aerobic, anaerobic and facultatively anaerobic bacteria. Experimental studies in animals and clinical trials indicate that antimicrobial therapy should provide adequate coverage for the whole range of isolates. Penicillins and cephalosporins with relatively limited activity against anaerobes have been associated with clinical failures in treating various types of mixed infections. Aminoglycosides are often used in combination with other drugs in the treatment of intra-abdominal infections. Recent studies have cast doubt on this practice because of increased resistance of Gram-negative bacilli to aminoglycosides and high rates of renal toxicity. Regimens that do not include an aminoglycoside have given good results in treatment of appendicitis, penetrating abdominal trauma, and peritonitis. Enterococci are frequently isolated from intra-abdominal infections, but evidence suggests that it is not necessary to direct treatment at this organism initially. PMID- 8449836 TI - Determinants of the activity of beta-lactamase inhibitor combinations. AB - Inhibitor combinations provide one strategy to overcome beta-lactamase-mediated resistance. Their success depends, obviously, on the inhibitor being able to bind and inactivate the beta-lactamase molecules. Clavulanate, sulbactam and tazobactam are irreversible inactivators of many beta-lactamases, forming covalent complexes which resist hydrolysis. 'Suicide' kinetics are seen with some, but not all, enzymes. All three compounds inactivate staphylococcal penicillinase, the chromosomal beta-lactamases of Proteus vulgaris and Bacteroides spp., and the Class IV beta-lactamases present in some klebsiellae. Tazobactam, but not the other compounds, has moderate activity against some Class I (AmpC) chromosomal beta-lactamases, notably that of Morganella morganii, but not that of Enterobacter cloacae. Both clavulanate and tazobactam are strong inhibitors of the widely distributed TEM and SHV plasmid-mediated beta lactamases; sulbactam is a weaker inhibitor. Other factors, aside from the affinity of the inhibitor for the enzyme, co-determine the success or failure of inhibition. Potentiation is most readily achieved if little enzyme is produced, and if the organism is very permeable to the inhibitor. Thus, resistance to inhibitor combinations is rare in strains of Haemophilus influenzae and Neisseria gonorrhoeae that produce TEM-beta-lactamase, but is commoner in enterobacteria that produce this enzyme, since these are less permeable and sometimes manufacture very large amounts of enzyme. The partner beta-lactam agent is also important. Irrespective of the inhibitor used, piperacillin is easier to protect against TEM beta-lactamases and the M. morganii Class I enzyme than are ampicillin, amoxycillin or ticarcillin. This may relate to the lower affinity of piperacillin for these enzymes, or to its greater affinity for the bacterial penicillin-binding proteins. Finally, pH can affect the degree of inhibition achieved with sulphones for some beta-lactamases, notably TEM-1. PMID- 8449837 TI - Prophylaxis at the margins. Proceedings of a meeting. Bishopstrowe, 9-10 May 1992. PMID- 8449838 TI - Antimicrobial prophylaxis in surgery: microbiological factors. AB - Various aspects of prophylaxis in surgery are discussed. The timing of antibiotic doses is analysed in relation to the Burke laboratory model and the lag-phase of bacterial growth. Areas where further data is required: the effect of locally applied antibiotics, protection against sources of organisms and new approaches to prophylaxis are discussed. The ecological effects of antibiotics are described in relation to prophylaxis. PMID- 8449839 TI - Antimicrobial prophylaxis during biliary endoscopic procedures. AB - Endoscopic retrograde cholangiopancreatography (ERCP) is a well-established technique and has considerable diagnostic value and therapeutic potential in patients with hepatobiliary disease. In experienced hands, ERCP is a safe procedure. The most important complications are pancreatitis, infection- ascending cholangitis and septicaemia--instrumental injury and haemorrhage. The reported incidence of bacteraemia complicating ERCP varies considerably (0.16 16%) but this may be due to differences in specimen collection and culture techniques. Clinically significant sepsis is the commonest cause of death due to ERCP with a case fatality rate of 8-20%. As the danger of sepsis was increasingly recognized, antibiotic prophylaxis was considered as routine policy in many centres; supporting evidence was retrospective. Significant differences between antibiotic and control groups are difficult to confirm in clinically controlled trials because of an insufficient number of patients and the low incidence of cholangitis and septicaemia. The optimum regimen is unknown and there is uncertainty regarding the duration of treatment required to provide adequate protection. Local variations in bacterial sensitivity should be taken into account when choosing the antimicrobial agent. In patients without clinical signs of biliary obstruction the risk of infection is low and prophylaxis may be unnecessary. PMID- 8449840 TI - Pharmacoeconomics of antimicrobial prophylaxis. AB - Pharmacoeconomic analysis of the prevention of infection is based on quantification of the benefits which result from prevention, rather than simple counting of the number of cases prevented. In general, benefits are best quantified as continuous variables which measure severity as well as occurrence, for example, cost of antibiotics prescribed is a useful continuous measure of severity to add to a discontinuous measure, such as number of patients who received antibiotics. Considerable progress has been made in the USA with the application of decision analysis to clarify the options available for dealing with a problem, the probability of good and bad outcomes for each choice and the utility which is associated with each outcome. These techniques deserve wide application. Much existing practice is based on limited, poor quality information about the occurrence and severity of infection. This situation can only be improved by wider application of standardized methods for definition of occurrence of infection and of underlying risk of infection. PMID- 8449841 TI - Pharmacokinetic aspects of antibacterial prophylaxis. AB - Effective prophylaxis against infection can only occur when the antibacterial achieves suitable concentrations at the site of potential infection. This review discusses how the pharmacokinetics of systemically applied prophylaxis and the factors governing the distribution of locally applied antibacterials influence the outcome of prophylactic therapy. While the choice of route of administration for systemic prophylaxis rarely poses a problem, the effective concentrations required at the site of potential infection are unclear and may possibly be less than those needed for therapy of established infection. In some tissues there may be special considerations for the access of antibacterial from the blood, although for the large majority of sites the evidence is that access occurs without difficulty and is perhaps only limited by plasma protein binding of antibacterial. Locally applied antibacterials may have difficulty in reaching their site of action but this can often be overcome by their application at very high concentrations. PMID- 8449842 TI - Prophylaxis for HIV-associated infections in the developing world. AB - Prophylaxis for specific HIV-associated infections has made a major difference in the industrialized world to patient survival and the quality of life. However, the HIV epidemic is spreading most rapidly in the poor developing world, where prophylaxis is neither currently used nor recommended. Streptococcus pneumoniae. Mycobacterium tuberculosis and non-typhi salmonellae are the pathogens responsible for much of the morbidity and mortality associated with HIV infection in the tropics. Because these problems often present relatively early in the course of the HIV disease, prophylaxis may be cost-effective and increase the years of productive life. Prevention of pneumococcal disease has not been considered a priority in the developing world. Penicillin chemoprophylaxis may be efficacious; immunization which is recommended for all HIV seropositive adults in the USA, has not been used. The importance of studies to test both efficacy and cost compared to benefit is discussed. The problem of HIV-associated tuberculosis is of major importance and several intervention studies are now in progress. The efficacy of chemoprophylaxis may be limited if the problem is largely acute infection rather than reactivated disease and if shown to be effective compliance will present a major operational difficulty. Systemic salmonellosis is greatly underdiagnosed but may be the leading cause of death. Recurrent infection can be prevented by chemoprophylaxis but this will be costly. The use of novel or currently unlicensed vaccines may eventually prove to be the most effective means of controlling the burden of disease and death caused by salmonellosis. PMID- 8449843 TI - Antibiotics and neutrophil function--potential immunomodulating activities. AB - The advent of cytokines as possible therapeutic agents has stimulated investigation of old and new antibiotics for their potential activity as immunomodulators over and above their primary bactericidal or bacteristatic activity. Such investigations have focused largely on in-vitro functions of peripheral blood cells such as polymorphonuclear leucocytes and monocytes. Graded doses of various antibiotics have been tested for their ability to affect functions such as chemotaxis, phagocytic ingestion and killing, as well as particular biochemical mechanisms, such as a generation of superoxide. These drugs have been shown to have no effect on host defences (beta-lactams), or depress immune function (tetracyclines and teicoplanin), or display synergy with the immune system (macrolides and quinolones), or enhance immune function (certain cephalosporins). In several instances, biological activity has been demonstrated at drug concentrations outside the therapeutic range. In addition, it has been recognized that a number of drugs can be concentrated within the phagocytic cells and, by so doing, are transported to the site of infection with consequent increased efficacy. It has also been demonstrated that subinhibitory concentrations of certain drugs can influence bacterial expression of structural and soluble virulence factors. Alterations of this kind have been shown to potentiate bacterial susceptibility to phagocytosis. Notwithstanding these in vitro examples of immunomodulation, definite proof of clinical benefit is still lacking. PMID- 8449844 TI - Antimicrobial prophylaxis in 'clean' surgery: hernia repair. AB - Antimicrobial prophylaxis is not traditionally employed for patients undergoing 'clean' surgery. The true rates of septic complications are grossly under reported for this group of patients, with up to 72% of all complications occurring, undetected by the surgical team, after discharge from hospital. The implied costs of these infections, coupled with the costs to both the patient and the community services, suggest that antimicrobial prophylaxis should be seriously considered for many types of 'clean' surgery. This can now be made both more straightforward and cost-effective by employing the oral route of administration. PMID- 8449845 TI - Perioperative antibiotic prophylaxis and wound infection following breast surgery. AB - The effectiveness of perioperative antibiotic prophylaxis against wound infections following breast surgery was investigated by meta-analysis of published data from a randomized clinical trial and an observational data set, which included a total of 2587 surgical procedures, including excisional biopsy, lumpectomy, mastectomy, reduction mammoplasty and axillary node dissection. There were 98 wound infections (3.8%). Prophylaxis was used for 44% (1141) of these procedures, cephalosporins accounted for 986 (86%) of these courses of antibiotics. Prophylaxis prevented 38% of infections, after controlling for operation type, duration of surgery and participation in the randomized trial (Mantel-Haenszel Odds Ratio = 0.62, 95% confidence interval = 0.40-0.95, P = 0.03). There was no significant variation in efficacy according to operation type or duration. We conclude that antibiotic prophylaxis significantly reduces the risk of postoperative wound infection following these commonly performed breast procedures. PMID- 8449846 TI - Antimicrobial prophylaxis in neurosurgery. AB - Attempts to reach conclusions concerning the efficacy of antimicrobial prophylaxis in neurosurgery have been frustrated by the paucity of clinical trials which cannot be invalidated by flaws in their design and/or execution. Although the data are inconclusive, the weight of evidence suggests that antibiotics probably exert a protective effect in clean, non-implant procedures, for which a first or second generation cephalosporin would be appropriate. No consensus has been reached regarding the benefits of prophylaxis to patients undergoing the implantation of a CSF shunt and surgeons will therefore need to come to a decision based on their own experiences; those who elect to give antibiotics will still be left with the problems of choosing the optimum regimen and route of administration. Nor can valid conclusions be drawn about the efficacy of prophylaxis in patients with dural fistulae; a rational and ethically supportable approach would be to withhold antibiotics and to monitor patients closely for the early signs of meningitis, instituting appropriate empirical therapy should this complication arise. PMID- 8449847 TI - Antibiotic prophylaxis in peripheral vascular and orthopaedic prosthetic surgery. AB - Peripheral vascular by-pass and orthopaedic joint replacement surgery have much in common. The consequences of infection are serious and occasionally fatal. The incidence of infection varies from 0.5% to 3% depending on the anatomical site; the infecting organisms and distribution of organisms are similar. In orthopaedics a clean theatre environment, high local concentrations of antibiotic in the cement and systemic antibiotic prophylaxis are well established methods of reducing infection rates and are supported by clinical trials. In contrast, scientific evidence supporting these three tenets is lacking for peripheral vascular surgery. There are wide variations in the choice of prophylaxis cover for peripheral vascular surgery and the first clinical cases of antibiotic containing graft material have only recently been described. The choice of an ideal antibiotic for the prophylaxis of infections associated with vascular surgery is debatable; wound and graft infections in those receiving antibiotic prophylaxis range from 0.9% to 5.8% and 0.0 to 0.9%, respectively. For both forms of surgery whether single dose, short course or longer periods of prophylaxis is preferred, it is agreed that the antibiotic must achieve adequate concentrations at the time of potential bacterial contamination. One of the limiting factors of single dose prophylaxis is the ability of the antibiotic to penetrate bone, soft tissue or haematoma. However, single dose prophylactic antibiotic cover in prosthetic surgery will attract increasing support whenever the criteria of spectrum and 'risk period' cover is fulfilled. This may help to contain the increase in multi-resistant bacteria, particularly staphylococci within the hospital ecosystem. Prolonged systemic administration can now be replaced by high local antibacterial activity at the site of prosthesis insertion via a bonded sealant or an impregnated cement. This permits high activity which can last for several weeks until all the lines are removed and tissue incorporation has become established. PMID- 8449848 TI - Chemoprophylaxis of bacterial meningitis. AB - Bacterial meningitis continues to be a life-threatening disease and an important cause of severe disability in otherwise healthy individuals. This article reviews the aspects related to the prevention of secondary cases. Our understanding about the factors leading to an epidemic and the identification of high risk groups remains limited. For this reason, chemoprophylaxis can be used only for the prevention of secondary cases once an index case has been identified. The objectives of prophylaxis are threefold: (i) to eliminate nasopharyngeal carriage in household contacts; (ii) to prevent contacts from acquiring the disease and (iii) to treat infection in those incubating the disease. Chemoprophylaxis can only achieve the first of these objectives. Nasopharyngeal carriage of meningococci and Haemophilus influenzae can be eradicated with the use of antibiotics and their advantages and disadvantages are discussed. Prophylaxis should be given to household members and kissing and saliva-exchanging contacts of a case of meningococcal meningitis. The decision to give prophylaxis to extended family contacts, close neighbour contacts or children attending day-care centres where a case has occurred is controversial. It does not alter the course of an epidemic and close contacts are liable to become reinfected soon after prophylaxis. Prophylaxis of H. influenzae should be given to households in which there is at least one child (other than the index case) under 48 months of age. There is no agreement on the need to provide chemoprophylaxis to children in day care centres because the risk of secondary infections is uncertain. An alternative to chemoprophylaxis is protective chemotherapy which can prevent the development of meningitis in individuals incubating the disease. PMID- 8449849 TI - Current and future trends in immunization against meningitis. AB - The progress in vaccines for Haemophilus influenzae type b infection is followed; it is the disadvantages of pure polysaccharide vaccines that have stimulated the development of the present generation of polysaccharide-protein conjugated vaccines. From extensive clinical trials it is apparent that these are very effective in preventing disease in children. Conjugated haemophilus vaccines were introduced into the routine immunization schedules in the UK in Autumn 1992. Meningococcal A and C polysaccharide vaccines, effective for epidemic disease, are only now being developed in a protein conjugated form with the prospect of protecting young children and producing durable immunity. Group B outer membrane based meningococcal vaccines produce only a low degree of protection and much further work is needed before even the optimum vaccine constituents of this organism can be identified. Vaccines to replace multivalent pneumococcal polysaccharide mixtures are only in the very earliest stages of development. PMID- 8449850 TI - Evaluating interventions with differential attrition: the importance of nonresponse mechanisms and use of follow-up data. AB - Evaluations of psychological interventions are often criticized because of differential attrition, which is cited as a severe threat to validity. The present study shows that differential attrition is not a problem unless the mechanism causing the attrition is inaccessible (unavailable for analysis). With a simulation study, we show that conclusions about program effects (a) are unbiased when there is no differential attrition, even with usual complete cases analysis; (b) may be severely biased when based on usual complete cases analyses and there is differential attrition; (c) are unbiased when based on the expectation-maximization (EM) algorithm, even when there is differential attrition, as long as the attrition mechanism is accessible; and (d) are biased, even with the EM algorithm, when the attrition mechanism is inaccessible. Following Little and Rubin (1987), we advocate the collection of new data from a random sample of subjects with initially missing data. On the basis of these data, we propose a simple correction to the EM algorithm estimates. In our study, the correction produced unbiased estimates of program effects parameters, even with an inaccessible attrition mechanism and substantial differential attrition. PMID- 8449851 TI - Cognitive processes in self-report responses: tests of item context effects in work attitude measures. AB - Much applied research relies on multi-item, self-report instruments. Drawing from recent cognitive theories, it was hypothesized that the items preceding a self report item, its item context, can generate cognitive carryover and prompt context-consistent responses. These hypotheses were tested in 2 investigations: a field experiment involving 431 employees of a nonprofit urban hospital and a laboratory replication involving 245 undergraduate business students who held full- or part-time jobs. In both studies, evaluatively neutral items were placed in specially arranged blocks of uniformly positive, uniformly negative, or randomly mixed items on 3 modified Job Descriptive Index scales. Responses to the neutral items differed across the 3 forms, but scale-level psychometric properties remained unchanged. The implications of these item- and scale-level results for a variety of self-report measures in organizations are discussed. PMID- 8449852 TI - Juror competence in civil trials: effects of preinstruction and evidence technicality. AB - Forty-eight jury-eligible adults heard 1 of 4 versions of a tort trial. The design combined high and moderate levels of evidence technicality and the placement of substantive judicial instructions either before or after evidence presentation. Jurors given instructions before hearing the evidence for liability and before the evidence for compensation made clear distinctions among 4 differentially worthy plaintiffs, whereas jurors instructed after evidence presentation were not able to distinguish among the plaintiffs. Preinstructions enabled jurors to devise a causal model, as measured by both verbal representation of the evidence and recognition tests, that contained more probative evidence and less nonprobative and evaluative information than the models constructed by jurors who were postinstructed. Preinstructed jurors were better able than postinstructed jurors to correctly reject recognition items not part of the trial text and to correctly identify items from the trial. PMID- 8449853 TI - Chronic demands and responsivity to challenge. AB - Certain kinds of arousal in response to challenge situations reflect conditioning that makes one adaptive to task demands. A growing literature implicates chronic stress as a factor degenerating this conditioning. This study investigated the relation between objective occupational demands to which workers were classified for at least 2 years and various indicators of adaptive responsivity to challenge situations. There were consistently significant and negative relations between the occupational exposures and cardiovascular and skin temperature responsivity to the acute challenges administered in the laboratory, the corresponding speed of recovery to baseline after removal of the challenge stimulus, and peripheral catecholamine changes during a work shift. PMID- 8449854 TI - Advances in the diagnosis of acute leukemia. AB - The diagnosis and monitoring of acute leukemia requires a multiparameter approach. Although the foundation of diagnosis continues to depend on morphologic and cytochemical determinations, the importance of immunologic, cytogenetic, and molecular classifications is beginning to be emphasized and addressed worldwide. In addition to aiding in the diagnosis of acute leukemia, the information gained by these studies increases the understanding of the pathobiology of these neoplasms. PMID- 8449855 TI - Acute promyelocytic leukemia. New insights into diagnosis and therapy. AB - The clinical and laboratory features of APL are distinct. APL has been effectively treated with anthracyclines. Postremission therapy and the addition of other cytotoxic agents in induction may be beneficial. Early deaths remain a problem despite improved management of coagulopathy. The cytogenetic marker, t(15;17), reflects a molecular defect that splices two transcription factors, PML and RARA, to produce chimeric mRNA and proteins. RA, the natural ligand for RARA, is able to induce CR by stimulating differentiation and maturation of the malignant cells. The addition of RA to the therapeutic armamentarium of the hematologic oncologist will allow further refinement of the management of these patients. Diagnosis is unambiguous because the molecular defect can be readily detected. Our understanding of the biology downstream of the affected genes is incomplete. Other retinoids may be more effective than all-trans RA and may avoid the fall in plasma levels seen in patients chronically treated with RA. Combination of retinoids with other cytokines or cytotoxic agents may decrease the immediate mortality and improve long-term DFS in APL. PMID- 8449856 TI - Therapy of the newly diagnosed adult with acute lymphoblastic leukemia. AB - Results for adult ALL have improved, with CR rates of 68% to 91% and a cure rate of 25% to 41%. The outcome for patients with T-ALL has especially improved, and the major drugs responsible are C and ara-C. Outcome for B-ALL has improved by using short intensive cycles including, among other drugs, C and high-dose MTX. The inferior outcome of adult ALL compared with childhood ALL seems related to the high proportion of Ph1/BCR-ABL positive ALL patients, which constitute about 30% in adults versus less than 5% in children. The major prognostic factors for survival in adult ALL are age, time to achieve CR, cytogenetic abnormalities, immunologic subtype, and WBC; these may serve as a guide for BMT in first CR. New approaches in the treatment of adult ALL include the use of HGFs, the use of biologic response modifiers, and the detection of MRD to tailor treatment decisions. PMID- 8449857 TI - Philadelphia chromosome-positive acute lymphoblastic leukemia. AB - The Philadelphia (Ph1) chromosome, ubiquitous in chronic myelogenous leukemia, also is commonly seen in acute lymphoblastic leukemia, particularly in adults. Whereas the presence of the Ph1 chromosome is associated with high white blood cell count and older age, the Ph1 chromosome is known to be an independent poor prognostic factor. Most Ph1+ patients are able to achieve remissions with intensive, systemic chemotherapy, but treatment is complicated by early relapse. Because of the uniformly poor prognosis and response to therapy in childhood and adult Ph1+ acute lymphoblastic leukemia, aggressive and investigational therapies should be considered early in the course of this disease. PMID- 8449858 TI - Allogeneic bone marrow transplantation for the treatment of adult acute leukemias. AB - Allogeneic BMT has been shown to be a highly effective therapy for both AML and ALL. With the availability of unrelated donors, continuing advances in the development of new and more effective transplant regimens, and the identification of agents such as the hematopoietic growth factors, alprostadil, and pentoxifylline to decrease the regimen related toxicities, BMT will become a viable option for a greater number of adults with acute leukemia. The optimal timing for BMT will continue to evolve, but based upon the currently available information, patients age 55 or less with AML with a high probability of relapse based upon cytogenetic abnormalities should be considered for transplantation in first remission if a related or unrelated donor can be identified. For patients at low risk for relapse (e.g., age 25 or less who have received high-dose intensification), transplantation can be delayed until documentation of early relapse. For patients with Ph1+ ALL or t(4;11), transplantation in first remission should be considered if a suitable related or unrelated donor is identified. Adults with ALL without adverse prognostic characteristics should be considered for transplantation at relapse or in second remission. PMID- 8449859 TI - Autologous bone marrow transplantation for adult acute leukemia. AB - In this review we have considered the role of ABMT for the acute leukemias. It is apparent from data around the world that ABMT is a curative therapy for patients with both AML and ALL after primary treatment failure. Other than allogeneic BMT, ABMT may be the only curative therapy following relapse, especially in AML. The role of ABMT in first CR is less well defined. There are few data to support the widespread use of ABMT in first CR for ALL. Moreover, the improved survival of adults with ALL with current intense multiagent regimens will probably obviate the need to continue clinical trials of ABMT for ALL in first CR. For patients with AML in first CR, however, it seems that ABMT may well lead to improved rates of DFS compared with chemotherapy alone. Almost every published report describes better DFS for patients who underwent ABMT compared with historical or contemporary controls who were treated with chemotherapy. One note of caution is that as chemotherapy evolves, the increment in survival currently observed from ABMT may diminish, thus rendering ABMT less obviously necessary. On the other hand, from an economic standpoint, ABMT could prove to be cost-effective, because a short, intense treatment that is effective may prove to be less costly than the current extended period of chemotherapy. Because ABMT is becoming safer, it would seem reasonable to continue its use in patients with AML at high risk for relapse (secondary AML, adverse cytogenetics, and so on) while awaiting the outcome of the randomized clinical trials currently underway that are seeking to define the role of ABMT for the general population of patients with AML after initial remission is achieved. Meanwhile, further definition of the relative value of the various purging regimens, preparative regimens, and adjunctive therapy (i.e., IL 2, mAb) warrants study. PMID- 8449860 TI - The discovery and development of new antileukemic drugs. AB - Despite the major advances that have been made over the past few decades in the management of adult acute leukemia, a substantial number of the patients still die from the underlying disease. Therefore, it is essential that we vigorously pursue efforts to discover and develop novel therapeutic agents for the treatment of leukemia. PMID- 8449861 TI - Growth factors in the management of adult acute leukemia. AB - This review has explored the various ways that growth factors may be used in the management of adult acute leukemia. Growth factors have the potential to reduce the morbidity and mortality of both induction and postremission therapy by enhancing hematopoietic recovery or, when used as an adjunct to standard antimicrobial therapy, reducing the infectious complications of chemotherapy. In addition, they may have favorable effects on the biology of leukemia either by recruitment of leukemic progenitors into cycle, rendering them more sensitive to the cytotoxic effects of chemotherapy, or by inducing the terminal differentiation of the leukemic clone. Finally, disruption of aberrant growth factor networks, thought to play a role in the pathogenesis of leukemia, may be a therapeutic strategy now that soluble receptors and receptor antagonists to such growth factors as IL-1 are available. Whether growth factors used in such ways will have beneficial, or in fact adverse, effects on the treatment outcome for acute leukemia is not yet known. As such, the use of growth factors in the management of adults with acute leukemia is still experimental and needs to be studied in the context of clinical trials. Perhaps the ultimate benefit to be derived from the study of these growth factors will be a deeper understanding of the genetic perturbations that define the leukemic state. The development of molecular therapeutic techniques, such as gene transfer technology and the use of antisense oligonucleotides, has paralleled our increasing knowledge of cytokines. The hope is that as we come to understand leukemia at the molecular level, we will be able to develop the new therapeutic tools necessary to increase the numbers of patients cured. PMID- 8449862 TI - Management of unusual presentations of acute leukemia. AB - Unusual patterns of presentation of acute leukemia are discussed, with an emphasis on the diagnostic and therapeutic challenges that they pose. Clinical syndromes reviewed include the leukostasis syndrome, disseminated intravascular coagulation, granulocytic sarcoma, central nervous system leukemia, leukemia cutis, Sweet's syndrome, pyoderma gangrenosum, and acute leukemia diagnosed during pregnancy. Each of these uncommon presentations of acute leukemia has a unique impact on patient management. PMID- 8449863 TI - Management of infection in patients with acute leukemia. AB - Substantial improvements have occurred in the infectious diseases management of patients with acute leukemia. It is now unusual for patients receiving initial induction chemotherapy at a major center to die of infectious complications without receiving an adequate course of antineoplastic treatment. Many patients also receive reinduction chemotherapy with prolonged periods of neutropenia without succumbing to major infectious complications. However, the area of management of infections in patients with acute leukemia has remained a dynamic process, with infection management issues that remain complex and controversial. PMID- 8449864 TI - Treatment of the newly diagnosed adult with de novo acute myeloid leukemia. AB - Recent studies suggest that the administration of intensive post-remission therapy, which includes high-dose cytarabine, results in a longer period of disease-free survival when compared with lower dose treatment. In view of these improved results, it is uncertain currently whether younger patients with acute myeloid leukemia (AML) in first remission should be offered such intensive chemotherapy or either allogeneic or autologous bone marrow transplantation. Currently ongoing clinical trials, laboratory-based prognostic factor analysis, and attempts at better understanding the pathophysiology of acute leukemia may provide more precise guidelines for choosing the best treatment among these alternatives for any given individual with AML in first remission. PMID- 8449865 TI - Characterization of paralogous and orthologous members of the superoxide dismutase gene family from genera of the halophilic archaebacteria. AB - Four species representing three genera of halophilic archaebacteria were examined for the presence of genomic sequences that encode proteins of the superoxide dismutase family. Three species, Halobacterium cutirubrum, Halobacterium sp. strain GRB, and Haloferax volcanii, contain duplicated (paralogous) genes of the sod family; a fourth species, Haloarcula marismortui, contains only a single gene. These seven genes were cloned and sequenced, and their transcripts were characterized by Northern (RNA) hybridization, S1 nuclease protection, and primer extension. The expression of one of the two genes in H. cutirubrum, Halobacterium sp. strain GRB, and Haloferax volcanii was shown to be elevated in the presence of paraquat, a generator of superoxide radicals. The other genes, including the single gene from Haloarcula marismortui, exhibited no elevated expression in the presence of paraquat. The 5' and 3' flanking regions of all the genes contain recognizable promoter and terminator elements that are appropriately positioned relative to the 5' and 3' transcript end sites. Between genera, the orthologous paraquat-responsive genes exhibit no sequence similarity in either their 5' or 3' flanking regions, whereas the orthologous nonresponsive genes exhibit limited sequence similarity but only in the 5' flanking region. Within the coding region, the two paralogous genes of Haloferax volcanii are virtually identical (99.5%) despite the absence of similarity in the flanking regions. In contrast, the paralogous genes of H. cutirubrum and Halobacterium sp. strain GRB are only about 87% identical. In the alignment of all seven sequences, there are nine codon positions where both the TCN and AGY serine codons are utilized; some or all of these may well be examples of convergent evolution. PMID- 8449866 TI - Structure, function, and evolution of the family of superoxide dismutase proteins from halophilic archaebacteria. AB - The protein sequences of seven members of the superoxide dismutase (SOD) family from halophilic archaebacteria have been aligned and compared with each other and with the homologous Mn and Fe SOD sequences from eubacteria and the methanogenic archaebacterium Methanobacterium thermoautotrophicum. Of 199 common residues in the SOD proteins from halophilic archaebacteria, 125 are conserved in all seven sequences, and 64 of these are encoded by single unique triplets. The 74 remaining positions exhibit a high degree of variability, and for almost half of these, the encoding triplets are connected by at least two nonsynonymous nucleotide substitutions. The majority of nucleotide substitutions within the seven genes are nonsynonymous and result in amino acid replacement in the respective protein; silent third-codon-position (synonymous) substitutions are unexpectedly rare. Halophilic SODs contain 30 specific residues that are not found at the corresponding positions of the methanogenic or eubacterial SOD proteins. Seven of these are replacements of highly conserved amino acids in eubacterial SODs that are believed to play an important role in the three dimensional structure of the protein. Residues implicated in formation of the active site, catalysis, and metal ion binding are conserved in all Mn and Fe SODs. Molecular phylogenies based on parsimony and neighbor-joining methods coherently group the halophile sequences but surprisingly fail to distinguish between the Mn SOD of Escherichia coli and the Fe SOD of M. thermoautotrophicum as the outgroup. These comparisons indicate that as a group, the SODs of halophilic archaebacteria have many unique and characteristic features. At the same time, the patterns of nucleotide substitution and amino acid replacement indicate that these genes and the proteins that they encode continue to be subject to strong and changing selection. This selection may be related to the presence of oxygen radicals and the inter- and intracellular composition and concentration of metal cations. PMID- 8449867 TI - DNA binding and bending are necessary but not sufficient for Fis-dependent activation of rrnB P1. AB - The Escherichia coli Fis protein binds to three sites in the upstream activation region of the rrnB P1 promoter and enhances transcription 5- to 10-fold in vivo. In this report, we investigate the mechanism of Fis-dependent activation of transcription. We show that stimulation of rrnB P1 transcription by Fis can occur on linear DNA templates and does not require DNA upstream of the promoter proximal Fis site I. Mutants of Fis defective for Hin-mediated recombination have been isolated previously and have defined an N-terminal domain required for DNA inversion by Hin in addition to the C-terminal domain which is required for DNA binding. Several of these mutants were found to be defective in stimulation of rrnB P1 transcription in vivo and in vitro. Activation-defective mutants fall into three classes: those that fail to bind to the upstream activation region, those that bind but fail to bend the DNA normally, and those that bind and bend but still fail to activate transcription. We conclude that it is unlikely that Fis functions by simply bringing upstream sequences or bound factors into the proximity of RNA polymerase to activate transcription. Rather, the data are most easily interpreted in terms of transcription activation by direct interactions between Fis and RNA polymerase, requiring precise positioning of the two proteins facilitated by bending of the DNA binding site. PMID- 8449868 TI - Escherichia coli ferredoxin NADP+ reductase: activation of E. coli anaerobic ribonucleotide reduction, cloning of the gene (fpr), and overexpression of the protein. AB - A specific ribonucleoside triphosphate reductase is induced in anaerobic Escherichia coli. This enzyme, as isolated, lacks activity in the test tube and can be activated anaerobically with S-adenosylmethionine, NADPH, and two previously uncharacterized E. coli fractions. The gene for one of these, previously named dA1, was cloned and sequenced. We found an open reading frame coding for a polypeptide of 248 amino acid residues, with a molecular weight of 27,645 and with an N-terminal segment identical to that determined by direct Edman degradation. In a Kohara library, the gene hybridized between positions 3590 and 3600 on the physical map of E. coli. The deduced amino acid sequence shows a high extent of sequence identity with that of various ferredoxin (flavodoxin) NADP+ reductases. We therefore conclude that dA1 is identical with E. coli ferredoxin (flavodoxin) NADP+ reductase. Biochemical evidence from a bacterial strain, now constructed and overproducing dA1 activity up to 100-fold, strongly supports this conclusion. The sequence of the gene shows an apparent overlap with the reported sequence of mvrA, previously suggested to be involved in the protection against superoxide (M. Morimyo, J. Bacteriol. 170:2136-2142, 1988). We suggest that a frameshift introduced during isolation or sequencing of mvrA caused an error in the determination of its sequence. PMID- 8449869 TI - Cloning and nucleotide sequence of the gene encoding the positive regulator (DmpR) of the phenol catabolic pathway encoded by pVI150 and identification of DmpR as a member of the NtrC family of transcriptional activators. AB - The catabolic plasmid pVI150 of Pseudomonas sp. strain CF600 encodes all the genetic information required for the regulated metabolism of phenol and some of its methyl-substituted derivatives. The structural dmp genes of the pathway are clustered in a single operon that lies just downstream of a -24 TGGC, -12 TTGC nif/ntr-like promoter sequence. Promoters of this class are recognized by a minor form of RNA polymerase utilizing sigma 54 (NtrA, RpoN). Primer extension analysis demonstrated that the dmp operon transcript initiates downstream of the -24, -12 promoter. Transposon insertion mutants, specifically defective in the regulation of the dmp operon, were isolated, and complementation of a phenol-utilization regulatory mutant was used to identify the regulatory locus, dmpR. The 67-kDa dmpR gene product alone was shown to be sufficient for activation of transcription from the dmp operon promoter. Nucleotide sequence determination revealed that DmpR belongs to the NtrC family of transcriptional activators that regulate transcription from -24, -12 promoters. The deduced amino acid sequence of DmpR has high homology (40 to 67% identity) with the central and carboxy terminal regions of these activators, which are believed to be involved in the interaction with the sigma 54 RNA polymerase and in DNA binding, respectively. The amino-terminal region of DmpR was found to share 64% identity with the amino terminal region of XylR, which is also a member of this family of activators. This region has been implicated in effector recognition of aromatic compounds that is required for the regulatory activity of XylR. PMID- 8449870 TI - Synthesis of lipopolysaccharide O side chains by Pseudomonas aeruginosa PAO1 requires the enzyme phosphomannomutase. AB - We have cloned a lipopolysaccharide (LPS) biosynthetic gene from Pseudomonas aeruginosa PAO1 that complements the defect in the production and incorporation of LPS O side chains in the LPS-rough strain AK1012. This gene was characterized by pulsed-field gel electrophoresis, deletion and restriction mapping of the cloned DNA, and biochemical analysis of the protein product. The cloned DNA was found to map to the 7-to-11-min region of the P. aeruginosa chromosome, and the gene needed for complementation of the LPS-rough phenotype was contained on a 2.6 kb HindIII-SacI fragment. This same size restriction fragment contains the alginate gene algC, which encodes the enzyme phosphomannomutase (PMM) and also maps to this region of the P. aeruginosa chromosome. The LPS-rough strain AK1012 was deficient in PMM activity, and this activity was restored to parental levels when the cloned gene was transferred to strain AK1012. In addition, the cloned gene could complement the PMM deficiency in the algC mutant strain 8858, and the cloned algC gene could restore the LPS-smooth phenotype to strain AK1012. These results indicate that the gene we have cloned is equivalent to the alginate gene algC. We designate this gene pmm to emphasize that it encodes the enzyme PMM, which has been shown to be essential for alginate production, and we demonstrate that PMM activity is required for the LPS-smooth phenotype in P. aeruginosa PAO1. PMID- 8449871 TI - Metabolism of 2,2'-dihydroxybiphenyl by Pseudomonas sp. strain HBP1: production and consumption of 2,2',3-trihydroxybiphenyl. AB - Cells of Pseudomonas sp. strain HBP1 grown on 2-hydroxy- or 2,2' dihydroxybiphenyl contain NADH-dependent monooxygenase activity that hydroxylates 2,2'-dihydroxybiphenyl. The product of this reaction was identified as 2,2',3 trihydroxybiphenyl by 1H nuclear magnetic resonance and mass spectrometry. Furthermore, the monooxygenase activity also hydroxylates 2,2',3 trihydroxybiphenyl at the C-3' position, yielding 2,2',3,3'-tetrahydroxybiphenyl as a product. An estradiol ring cleavage dioxygenase activity that acts on both 2,2',3-tri- and 2,2',3,3'-tetrahydroxybiphenyl was partially purified. Both substrates yielded yellow meta-cleavage compounds that were identified as 2 hydroxy-6-(2-hydroxyphenyl)-6-oxo-2,4-hexadienoic acid and 2-hydroxy-6-(2,3 dihydroxyphenyl)-6-oxo-2,4-hexadienoic acid, respectively, by gas chromatography mass spectrometry analysis of their respective trimethylsilyl derivatives. The meta-cleavage products were not stable in aqueous incubation mixtures but gave rise to their cyclization products, 3-(chroman-4-on-2-yl)pyruvate and 3-(8 hydroxychroman-4-on-2-yl)pyruvate, respectively. In contrast to the meta-cleavage compounds, which were turned over to salicylic acid and 2,3-dihydroxybenzoic acid, the cyclization products are not substrates to the meta-cleavage product hydrolase activity. NADH-dependent salicylate monooxygenase activity catalyzed the conversions of salicylic acid and 2,3-dihydroxybenzoic acid to catechol and pyrogallol, respectively. The partially purified estradiol ring cleavage dioxygenase activity that acted on the hydroxybiphenyls also produced 2 hydroxymuconic semialdehyde and 2-hydroxymuconic acid from catechol and pyrogallol, respectively. PMID- 8449872 TI - Cloning, nucleotide sequence, and regulatory analysis of the Lactococcus lactis dnaJ gene. AB - The dnaJ gene of Lactococcus lactis was isolated from a genomic library of L. lactis NIZO R5 and cloned into pUC19. Nucleotide sequencing revealed an open reading frame of 1,137 bp in length, encoding a protein of 379 amino acids. The deduced amino acid sequence showed homology to the DnaJ proteins of Escherichia coli, Mycobacterium tuberculosis, Bacillus subtilis, and Clostridium acetobutylicum. The level of the dnaJ monocistronic mRNA increased approximately threefold after heat shock. The transcription initiation site of the dnaJ gene was determined and appeared to be preceded by a typical gram-positive vegetative promoter sequence (TTGCCA-17 bp-TAAAAT). Upstream of the promoter region, an inverted repeat is located that is identical to those detected upstream of heat shock genes of other gram-positive organisms. A transcriptional fusion between the dnaJ expression signals and a usp45-amyS secretion cassette caused a significant increase in alpha-amylase activity after heat shock induction. Deletion mutagenesis showed that the inverted repeat is involved in heat shock regulation of the dnaJ gene. The conservation of this palindromic sequence in gram-positive heat shock genes suggests a common regulatory pathway distinct from the system used in gram-negative bacteria. PMID- 8449873 TI - A two-component regulatory system required for copper-inducible expression of the copper resistance operon of Pseudomonas syringae. AB - Specific induction of the copper resistance operon (cop) promoter from Pseudomonas syringae was measured by beta-galactosidase production from a cop promoter-lacZ fusion. Induction of the cop promoter in P. syringae pv. syringae required trans-acting factors from copper resistance plasmid pPT23D, from which cop was originally cloned. Tn5 mutagenesis of pPT23D was used to localize two complementation groups immediately downstream from copABCD. Cloning and sequencing of the DNA in this region revealed two genes, copR and copS, expressed in the same orientation as the cop operon but from a separate constitutive promoter. The amino acid sequence deduced from these genes showed distinct similarities to known two-component regulatory systems, including PhoB-PhoR and OmpR-EnvZ. In addition, CopR showed strong similarity to copper resistance activator protein PcoR from Escherichia coli. Functional chromosomal homologs to copRS activated the cop promoter, in a copper-inducible manner, in copper resistant or -sensitive strains of P. syringae pv. tomato and other Pseudomonas species. This implies that copper-inducible gene regulation is associated with a common chromosomally encoded function, as well as plasmid-borne copper resistance, in Pseudomonas spp. PMID- 8449874 TI - Phase variation in Xenorhabdus luminescens: cloning and sequencing of the lipase gene and analysis of its expression in primary and secondary phases of the bacterium. AB - The phenomenon of phase variation in the insect-pathogenic bacterium Xenorhabdus luminescens was investigated. Differential activity of the lipase enzyme (EC 3.1.1.3) was observed between the two phases of the bacteria. The enzyme was found to be secreted into the culture medium, and about five to six times greater specific activity was secreted by the primary phase than by the secondary form. The lipase gene (lip-1) was cloned and sequenced. The data imply that there is only a single Tween 80-utilizing lipase gene in X. luminescens K122. The sequence revealed a translation product of 645 amino acids, from which a hydrophobic leader sequence of 24 amino acids is removed during processing. The structure of the gene was shown to be the same in the primary and secondary forms of X. luminescens. In addition, transcription was found to start at the same position, 169 bp upstream of the translation initiation codon, in the two forms of the bacteria. Equal amounts of lipase RNA accumulated in the two forms, and at least as much lipase protein was secreted by the secondary form as by the primary. This suggests that the difference in specific activity between the enzymes secreted by the two phases probably arises from a posttranslational type of regulation. PMID- 8449875 TI - Induction of the lambda receptor is essential for effective uptake of trehalose in Escherichia coli. AB - Trehalose transport in Escherichia coli after growth at low osmolarity is mediated by enzyme IITre of the phosphotransferase system (W. Boos, U. Ehmann, H. Forkl, W. Klein, M. Rimmele, and P. Postma, J. Bacteriol. 172:3450-3461, 1990). The apparent Km (16 microM) of trehalose uptake is low. Since trehalose is a good source of carbon and the apparent affinity of the uptake system is high, it was surprising that the disaccharide trehalose [O-alpha-D-glucosyl(1-1)-alpha-D glucoside] has no problems diffusing through the outer membrane at high enough rates to allow full growth, particularly at low substrate concentrations. Here we show that induction of the maltose regulon is required for efficient utilization of trehalose. malT mutants that lack expression of all maltose genes, as well as lamB mutants that lack only the lambda receptor (maltoporin), still grow on trehalose at the usual high (10 mM) trehalose concentrations in agar plates, but they exhibit the half-maximal rate of trehalose uptake at concentrations that are 50-fold higher than in the wild-type (malT+) strain. The maltose system is induced by trehalose to about 30% of the fully induced level reached when grown in the presence of maltose in a malT+ strain or when grown on glycerol in a maltose-constitutive strain [malT(Con)]. The 30% level of maximal expression is sufficient for maximal trehalose utilization, since there is no difference in the concentration of trehalose required for the half-maximal rate of uptake in trehalose-grown strains with the wild-type gene (malT+) or with strains constitutive for the maltose system [malT(Con)]. In contrast, when the expression of the lambda receptor is reduced to less than 20% of the maximal level, trehalose uptake becomes less efficient. Induction of the maltose system by trehalose requires metabolism of trehalose. Mutants lacking amylotrehalase, the key enzyme in trehalose utilization, accumulate trehalose but do not induce the maltose system. PMID- 8449876 TI - Interaction of six global transcription regulators in expression of manganese superoxide dismutase in Escherichia coli K-12. AB - Transcription of the sodA gene of Escherichia coli, which encodes manganese superoxide dismutase, is governed by six global regulators: the product of the soxRS locus (superoxide response) and mutated alleles of the soxQ locus (such as cfxB) act as activators; the products of the fur (ferric uptake regulation), arcA (aerobic regulation control), and fnr (fumarate nitrate reductase) genes and the integration host factor (IHF) negatively regulate sodA. The action of these effectors on the sodA promoter was investigated by using chromosomal sodA-lacZ operon fusions with intact or deleted promoters, different environmental conditions, and strains carrying different combinations of null mutations in the effector genes. The data allow us to assign target regions in the sodA promoter for activation by SoxRS and CfxB and for repression by Fur and ArcA. In aerobiosis, activation of sodA transcription by SoxRS was compatible with CfxB activation or Fur repression, whereas cfxB and fur controls were mutually exclusive. Repression by Fnr appeared, at least in part, to be ArcA dependent. IHF enhanced aerobic Fur repression, and in the absence of Fur, it enhanced anaerobic repression by ArcA. The DNA targets for Fur (encompassing the -35 region) and ArcA (from and downstream of the -35 region) appear to overlap, suggesting that Fur and ArcA repressions are mutually exclusive. Fur (in response to the iron pool) or ArcA, acting with Fnr and IHF (in response to the redox state of the cells), can block anaerobic sodA-lacZ expression with about equivalent efficiencies. The possible biological significance of this result is discussed. PMID- 8449877 TI - The patB gene product, required for growth of the cyanobacterium Anabaena sp. strain PCC 7120 under nitrogen-limiting conditions, contains ferredoxin and helix turn-helix domains. AB - A mutant of Anabaena sp. strain PCC 7120, called PAT-2, that grows poorly under nitrogen-fixing conditions, has been isolated. The heterocysts of the mutant strain develop much more slowly than those of the wild type and are spaced more closely in an older culture of the mutant than in the wild type. The wild-type gene that complements the mutation in PAT-2, called patB, was isolated and characterized. The predicted 529-amino-acid PatB protein contains a region very similar to the Fe4S4 bacterial-type ferredoxins near its N terminus and a helix turn-helix motif near its C terminus. This pattern of domains resembles those of transcriptional regulators in both prokaryotes and eukaryotes. The mutation in strain PAT-2 is the deletion of G at nucleotide 1342 in the patB gene, resulting in the loss of a 62-amino-acid fragment from the C terminus of the PatB protein, including the helix-turn-helix motif. PMID- 8449878 TI - Cloning and characterization of a gene required for assembly of the Bacillus subtilis spore coat. AB - During endospore formation in Bacillus subtilis, approximately a dozen proteins are synthesized and assembled around the prespore to form a protective coat. Little is known about the assembly process, but several of the genes encoding these coat proteins are expressed in the mother cell compartment, where the proteins accumulate on the outer side of the developing endospore. Transcription of these genes is directed by the mother cell-specific sigma factor, sigma K, during the later stages of endospore development. sigma E may direct expression of the genes that encode proteins that function in the earliest stages of coat assembly. By screening for sigma E-dependent promoters, we cloned a gene, designated spoVID, required for assembly of a normal spore coat. Expression of spoVID was initiated at about the second hour of sporulation and continued throughout development from a sigma E-dependent promoter. The spoVID gene was located on the B. subtilis chromosome just downstream of the previously characterized hemAXCDBL operon and is predicted to encode an extremely acidic protein with 575 residues. Insertion mutants of spoVID produced refractile spores that were resistant to heat and to chloroform but were sensitive to lysozyme. Electron microscopic examination of sporulating spoVID mutant cells revealed normal morphological development up to about the third hour of sporulation. However, during the later stages of development the coat proteins assembled into aberrant structures that occurred freely in the mother cell cytoplasm and that consisted of reiterations of the single inner and outer layers that normally make up the spore coat. PMID- 8449879 TI - Possible role of a choline-containing teichoic acid in the maintenance of normal cell shape and physiology in Streptococcus oralis. AB - Streptococcus oralis ATCC 35037 took up radioactively labeled choline from growth medium. Most of the choline (80 to 90%) was incorporated into the cell wall teichoic acid, and about 10% was localized in the plasma membrane. While cells grew in choline-free medium, they did so at slow rates and produced cell walls with greatly reduced amounts of phosphate and no detectable choline. Cells grown in choline-free medium had grossly abnormal shape and size. Both biochemical and morphological abnormalities were reversible by addition of choline to the medium. PMID- 8449880 TI - The Agrobacterium tumefaciens virB4 gene product is an essential virulence protein requiring an intact nucleoside triphosphate-binding domain. AB - Products of the approximately 9.5-kb virB operon are proposed to direct the export of T-DNA/protein complexes across the Agrobacterium tumefaciens envelope en route to plant cells. The presence of conserved nucleoside triphosphate (NTP) binding domains in VirB4 and VirB11 suggests that one or both proteins couple energy, via NTP hydrolysis, to T-complex transport. To assess the importance of VirB4 for virulence, a nonpolar virB4 null mutation was introduced into the pTiA6NC plasmid of strain A348. The 2.37-kb virB4 coding sequence was deleted precisely by oligonucleotide-directed mutagenesis in vitro. The resulting delta virB4 mutation was exchanged for the wild-type allele by two sequential recombination events with the counterselectable Bacillus subtilis sacB gene. Two derivatives, A348 delta B4.4 and A348 delta B4.5, sustained a nonpolar deletion of the wild-type virB4 allele, as judged by Southern blot hybridization and immunoblot analyses with antibodies specific for VirB4, VirB5, VirB10, and VirB11. Transcription of wild-type virB4 from the lac promoter restored virulence to the nonpolar null mutants on a variety of dicotyledonous species, establishing virB4 as an essential virulence gene. A substitution of glutamine for Lys-439 and a deletion of Gly-438, Lys-439, and Thr-440 within the glycine-rich NTP-binding domain (Gly-Pro-Iso-Gly-Arg-Gly-Lys-Thr) abolished complementation of A348 delta B4.4 or A348 delta B4.5, demonstrating that an intact NTP-binding domain is critical for VirB4 function. Merodiploids expressing both the mutant and wild type virB4 alleles exhibited lower virulence than A348, suggesting that VirB4, a cytoplasmic membrane protein, may contribute as a homo- or heteromultimer to A. tumefaciens virulence. PMID- 8449882 TI - Characterization of genetic elements required for site-specific integration of the temperate lactococcal bacteriophage phi LC3 and construction of integration negative phi LC3 mutants. AB - The genetic elements required for the integration of the temperate lactococcal bacteriophage phi LC3 into the chromosome of its bacterial host, Lactococcus lactis subsp. cremoris, were identified and characterized. The phi LC3 phage attachment site, attP, was mapped and sequenced. DNA sequence analysis of attP and of the bacterial attachment site, attB, as well as the two phage-host junctions, attR and attL, in the chromosome of a phi LC3 lysogen, identified a 9 bp common core region, 5'-TTCTTCATG'-3, within which the strand exchange reaction takes place during integration. The attB core sequence is located within the C terminal part of an open reading frame of unknown function. The phi LC3 integrase gene (int), encoding the phi LC3 site-specific recombinase, was identified and is located adjacent to attP. The phi LC3 Int protein, as deduced from the nucleotide sequence, is a basic protein of 374 amino acids that shares significant sequence similarity with other site-specific recombinases of the integrase family. Phage phi LC3 int- and int-attP-defective mutants, conferring an abortive lysogenic phenotype, were constructed. PMID- 8449881 TI - Molecular cloning and characterization of the Bacillus subtilis spore photoproduct lyase (spl) gene, which is involved in repair of UV radiation induced DNA damage during spore germination. AB - Upon UV irradiation, Bacillus subtilis spore DNA accumulates the novel thymine dimer 5-thyminyl-5,6-dihydrothymine. Spores can repair this "spore photoproduct" (SP) upon germination either by the uvr-mediated general excision repair pathway or by the SP-specific spl pathway, which involves in situ monomerization of SP to two thymines by an enzyme named SP lyase. Mutants lacking both repair pathways produce spores that are extremely sensitive to UV. For cloning DNA that can repair a mutation in the spl pathway called spl-1, a library of EcoRI fragments of chromosomal DNA from B. subtilis 168 was constructed in integrative plasmid pJH101 and introduced by transformation into a mutant B. subtilis strain that carries both the uvrA42 and spl-1 mutations, and transformants whose spores exhibited UV resistance were selected by UV irradiation. With a combination of genetic and physical mapping techniques, the DNA responsible for the restoration of UV resistance was shown to be present on a 2.3-kb EcoRI-HindIII fragment that was mapped to a new locus in the metC-pyrD region of the B. subtilis chromosome immediately downstream from the pstI gene. The spl coding sequence was localized on the cloned fragment by analysis of in vitro-generated deletions and by nucleotide sequencing. The spl nucleotide sequence contains an open reading frame capable of encoding a 40-kDa polypeptide that shows regional amino acid sequence homology to DNA photolyases from a number of bacteria and fungi. PMID- 8449884 TI - A mutational analysis of the structural basis for transcriptional activation and monomer-monomer interaction in the TyrR system of Escherichia coli K-12. AB - In response to the binding of tyrosine or phenylalanine, the TyrR protein (513 amino acids) activates certain promoters and represses others. In a previous study (J. Cui and R. L. Somerville, J. Bacteriol. 175:303-306, 1993), it was shown that promoter activation was selectively abolished in mutant proteins lacking amino acid residues 2 to 9. An additional series of constructs that encoded mutant TyrR proteins having deletions or point mutations near the N terminus were analyzed. Residues Arg-2 and Leu-3 were shown to be critical for the activation of the mtr promoter. In confirmation of previous findings, none of the activation-defective mutant TyrR proteins had lost significant repression function. The TyrR protein was shown by chemical cross-linking to be dimeric. The polypeptide segments critical for dimer formation in vivo were identified by evaluating the negative dominance phenotypes of a series of mutant proteins, all defective in DNA binding, lacking progressively greater numbers of amino acid residues from either the N terminus or the C terminus. Amino acid residues 194 to 438 were found to contain all of the essential dimerization determinants. PMID- 8449883 TI - A genetic analysis of various functions of the TyrR protein of Escherichia coli. AB - The TyrR protein is involved in both repression and activation of the genes of the TyrR regulon. Correction of an error in a previously published sequence has revealed a Cro-like helix-turn-helix DNA-binding domain near the carboxyl terminus. Site-directed mutagenesis in this region has generated a number of mutants that can no longer repress or activate. Deletions of amino acid residues 5 to 42 produced a protein that could repress but not activate. The central domain of TyrR contains an ATP-binding site and is homologous with the NtrC family of activator proteins. A mutation to site A of the ATP-binding site and other mutations in this region affect tyrosine-mediated repression but do not prevent activation or phenylalanine-mediated repression of aroG. PMID- 8449885 TI - Interaction between the Chlamydia trachomatis histone H1-like protein (Hc1) and DNA. AB - The gene encoding the Chlamydia trachomatis histone H1-like protein (Hc1) from serovar L2 was cloned into Escherichia coli by use of expression vector pET11d. In this vector, transcription of the gene is under the control of a bacteriophage T7 promoter, and T7 RNA polymerase is inducible in the host. Following induction, the E. coli cells were lysed gently. Gel filtration of the lysate revealed comigration of DNA and Hc1 in the voided volume. Electron microscopy revealed the DNA to be complexed with protein in large aggregates, often in the form of spherical bodies. Purified recombinant Hc1 maintained its DNA-binding capacity and was able at high concentrations to form condensed aggregates with DNA (one molecule of Hc1 per base pair) independently of the form or size of the DNA but with a slight preference for supercoiled DNA. Hc1 alone is thus able to package DNA into condensed spherical bodies. PMID- 8449886 TI - In vivo and in vitro footprinting of a light-regulated promoter in the cyanobacterium Fremyella diplosiphon. AB - Certain filamentous cyanobacteria, such as Fremyella diplosiphon, modulate the components of their light-harvesting complexes, the phycobilisomes, and undergo complex morphological changes in response to the wavelength of incident light, or light quality. The operon encoding the subunits of phycoerythrin, cpeBA, is transcriptionally activated in green light and is expressed at very low levels in red light. To begin elucidating the signal transduction pathway between the detection of specific light wavelengths and changes in gene expression, we have used in vivo footprinting to show that a protein is bound to the region upstream of the cpeBA transcription start site in both red and green light: two guanosine residues at -55 and -65 bp are protected from dimethyl sulfate modification in vivo. Using DNA mobility shift gel electrophoresis, we have shown that partially purified extracts of F. diplosiphon from both red and green light contain DNA binding activity specific for the cpeBA promoter region. Using in vitro footprinting with dimethyl sulfate and DNase I, we have defined a binding site for this putative transcription factor, designated PepB (phycoerythrin promoter binding protein), that extends from -67 to -45 bp on the upper strand and from 62 to -45 bp on the bottom strand, relative to the transcription start site. The binding site includes two hexameric direct repeats separated by 4 bp, TTGTTAN4TTGTTA. We conclude from these results that PepB is bound to the region upstream of the cpeBA promoter in F. diplosiphon in both red and green light. Therefore, additional factors or protein modifications must be required to allow light-regulated transcription of this operon. PMID- 8449887 TI - Electron microscopic analysis and structural characterization of novel NADP(H) containing methanol: N,N'-dimethyl-4-nitrosoaniline oxidoreductases from the gram positive methylotrophic bacteria Amycolatopsis methanolica and Mycobacterium gastri MB19. AB - The quaternary protein structure of two methanol:N,N'-dimethyl-4-nitrosoaniline (NDMA) oxidoreductases purified from Amycolatopsis methanolica and Mycobacterium gastri MB19 was analyzed by electron microscopy and image processing. The enzymes are decameric proteins (displaying fivefold symmetry) with estimated molecular masses of 490 to 500 kDa based on their subunit molecular masses of 49 to 50 kDa. Both methanol:NDMA oxidoreductases possess a tightly but noncovalently bound NADP(H) cofactor at an NADPH-to-subunit molar ratio of 0.7. These cofactors are redox active toward alcohol and aldehyde substrates. Both enzymes contain significant amounts of Zn2+ and Mg2+ ions. The primary amino acid sequences of the A. methanolica and M. gastri MB19 methanol:NDMA oxidoreductases share a high degree of identity, as indicated by N-terminal sequence analysis (63% identity among the first 27 N-terminal amino acids), internal peptide sequence analysis, and overall amino acid composition. The amino acid sequence analysis also revealed significant similarity to a decameric methanol dehydrogenase of Bacillus methanolicus C1. PMID- 8449888 TI - Bioenergetics of sulfur reduction in the hyperthermophilic archaeon Pyrococcus furiosus. AB - The bioenergetic role of the reduction of elemental sulfur (S0) in the hyperthermophilic archaeon (formerly archaebacterium) Pyrococcus furiosus was investigated with chemostat cultures with maltose as the limiting carbon source. The maximal yield coefficient was 99.8 g (dry weight) of cells (cdw) per mol of maltose in the presence of S0 but only 51.3 g (cdw) per mol of maltose if S0 was omitted. However, the corresponding maintenance coefficients were not found to be significantly different. The primary fermentation products detected were H2, CO2, and acetate, together with H2S, when S0 was also added to the growth medium. If H2S was summed with H2 to represent total reducing equivalents released during fermentation, the presence of S0 had no significant effect on the pattern of fermentation products. In addition, the presence of S0 did not significantly affect the specific activities in cell extracts of hydrogenase, sulfur reductase, alpha-glucosidase, or protease. These results suggest either that S0 reduction is an energy-conserving reaction, i.e., S0 respiration, or that S0 has a stimulatory effect on or helps overcome a process that is yield limiting. A modification of the Entner-Doudoroff glycolytic pathway has been proposed as the primary route of glucose catabolism in P. furiosus (S. Mukund and M. W. W. Adams, J. Biol. Chem. 266:14208-14216, 1991). Operation of this pathway should yield 4 mol of ATP per mol of maltose oxidized, from which one can calculate a value of 12.9 g (cdw) per mol of ATP for non-S0 growth. Comparison of this value to the yield data for growth in the presence of S0 reduction is equivalent to an ATP yield of 0.5 mol of ATP per mol of S0 reduced. Possible mechanism to account for this apparent energy conservation are discussed. PMID- 8449889 TI - Cloning and characterization of Pseudomonas sp. strain DNT genes for 2,4 dinitrotoluene degradation. AB - The degradation of 2,4-dinitrotoluene (DNT) by Pseudomonas sp. strain DNT is initiated by a dioxygenase attack to yield 4-methyl-5-nitrocatechol (MNC) and nitrite. Subsequent oxidation of MNC by a monooxygenase results in the removal of the second molecule of nitrite, and further enzymatic reactions lead to ring fission. Initial studies on the molecular basis of DNT degradation in this strain revealed the presence of three plasmids. Mitomycin-derived mutants deficient in either DNT dioxygenase only or DNT dioxygenase and MNC monooxygenase were isolated. Plasmid profiles of mutant strains suggested that the mutations resulted from deletions in the largest plasmid. Total plasmid DNA partially digested by EcoRI was cloned into a broad-host-range cosmid vector, pCP13. Recombinant clones containing genes encoding DNT dioxygenase, MNC monooxygenase, and 2,4,5-trihydroxytoluene oxygenase were characterized by identification of reaction products and the ability to complement mutants. Subcloning analysis suggests that the DNT dioxygenase is a multicomponent enzyme system and that the genes for the DNT pathway are organized in at least three different operons. PMID- 8449890 TI - The final step of peptidoglycan subunit assembly in Escherichia coli occurs in the cytoplasm. AB - The murG gene of Escherichia coli encodes the N-acetylglucosaminyltransferase responsible for the final step in the formation of the lipid-linked disaccharide pentapeptide subunit of peptidoglycan. Using trypsin to probe maxicell spheroplasts, we show that this enzyme is peripherally associated with the inner face of the cytoplasmic membrane. Therefore, the peptidoglycan subunit is completely assembled before it traverses the cytoplasmic membrane. PMID- 8449891 TI - Ribosomal protein S1 and NusA protein complexed to recombination protein beta of phage lambda. AB - The red genes of bacteriophage lambda specify two proteins, exonuclease and beta protein, which are essential for general recombination of lambda in recA cells. Earlier studies suggested that these proteins form an equimolar complex (C. M. Radding, J. Rosenweig, F. Richards, and E. Cassuto, J. Biol. Chem. 246:2510-2512, 1971). A more recent study indicated that beta protein forms a strong complex with an unknown polypeptide of 70 kDa (K. Muniyappa and C. M. Radding, J. Biol. Chem. 261:7472-7478, 1986). In the present study, in addition to the complex of beta and the 70-kDa protein, a new association of beta protein with a 65-kDa protein was observed. N-terminal sequencing identified these proteins as host encoded ribosomal protein S1 and transcription terminator protein NusA. PMID- 8449892 TI - MsmE, a lipoprotein involved in sugar transport in Streptococcus mutans. AB - Metabolic labelling by [14C]palmitic acid showed that growth of Streptococcus mutans LT11 in raffinose, an inducer of the msm operon, resulted in increased production of a 45-kDa lipoprotein corresponding to MsmE, which is believed to be a sugar-binding protein. MsmE was also labelled when an msmE clone was expressed in Escherichia coli. The presence of a lipid anchor on MsmE provides a likely explanation of how the sugar-binding protein component of the msm binding protein dependent multiple sugar transport system is retained at the cell surface. PMID- 8449893 TI - The filamentous bacteriophage assembly proteins require the bacterial SecA protein for correct localization to the membrane. AB - The noncapsid assembly proteins pI and pI of the filamentous bacteriophage f1 are inserted into the inner membrane of Escherichia coli via an internal signal sequence. Inhibition of the activity of SecA with low concentrations of sodium azide results in rapid accumulation of pI and pI proteins in the cytoplasm. However, both proteins are inserted into the membrane under the same conditions when synthesized in bacteria containing a secA azide resistance mutation. The other noncapsid assembly protein, pIV, is an outer membrane protein synthesized with a cleavable signal sequence. Wild-type bacteria accumulate the precursor to pIV when protein synthesis is in the presence of low concentrations of sodium azide. These results suggest that the f1 bacteriophage assembly proteins require SecA and consequently the bacterial Sec system to reach their proper membrane location. PMID- 8449894 TI - Characterization of a plasmid-encoded urease gene cluster found in members of the family Enterobacteriaceae. AB - Plasmid-encoded urease gene clusters found in uropathogenic isolates of Escherichia coli, Providencia stuartii, and Salmonella cubana demonstrated DNA homology, similar positions of restriction endonuclease cleavage sites, and manners of urease expression and therefore represent the same locus. DNA sequence analysis indicated that the plasmid-encoded urease genes are closely related to the Proteus mirabilis urease genes. PMID- 8449895 TI - Ganglioside metabolism. Enzymology, Topology, and regulation. PMID- 8449896 TI - Brefeldin A reversibly inhibits secretion in Saccharomyces cerevisiae. AB - Brefeldin A has proven to be a useful pharmacologic tool, which, when added to mammalian cells, results in a block in secretion as well as the structural disruption of specific intracellular organelles. In spite of our understanding of some of the biochemistry underlying the action of brefeldin A, the most proximal molecular target(s) of the drug remain elusive. In attempting to address this problem, a genetic approach will undoubtedly prove useful and complementary to the biochemical identification of such a site(s). As a result of the relatively resistant nature of wild-type Saccharomyces cerevisiae to brefeldin A, an approach utilizing yeast genetics has not been possible. We report the selective sensitivity of three drug-sensitive strains of S. cerevisiae (ise-1, ISE-2, and erg6) with enhanced membrane permeability allowing uptake of brefeldin A. Upon addition of the drug, growth is dramatically inhibited and invertase secretion is rapidly, specifically, and reversibly blocked at the level of the endoplasmic reticulum. In addition, only structural analogues of brefeldin A effective in mammalian cells are active in these yeast strains. PMID- 8449897 TI - Role of myocyte-specific enhancer-binding factor (MEF-2) in transcriptional regulation of the alpha-cardiac myosin heavy chain gene. AB - The intergenic region between the mouse alpha-cardiac myosin heavy chain and beta myosin heavy chain genes has previously been shown to direct expression of the bacterial chloramphenicol acetyltransferase reporter gene in transgenic mice in a tissue-specific manner. Sequence analyses located a putative myocyte-specific enhancer-binding factor (MEF-2) site situated in the regulatory region of this gene proximal to the start site of transcription. The role of this element in directing the cardiac compartment-specific expression of the transgene was assessed. The polymerase chain reaction was used to perform substitution mutagenesis of the MEF-2 binding site, and lack of MEF-2 binding was confirmed by gel retardation assays. The resultant construct was used to generate transgenic mice. Surprisingly, transgene expression was not down-regulated, but was significantly increased in the hearts of the MEF-2 mutant mice. In addition, cardiac-specific expression of the transgene was perturbed with significant levels of ectopic expression occurring in the aorta. PMID- 8449898 TI - Glucocorticoid receptor-cAMP response element-binding protein interaction and the response of the phosphoenolpyruvate carboxykinase gene to glucocorticoids. AB - The phosphoenolpyruvate carboxykinase (PEPCK) gene encodes the rate-limiting enzyme in gluconeogenesis. Glucocorticoids enhance PEPCK gene expression through a multicomponent regulatory complex. We show that a full response to glucocorticoids requires two DNA segments: 1) a glucocorticoid response unit (GRU), centered at about position -400, which contains two accessory factor elements (AF1 and AF2) and two glucocorticoid receptor binding sites (GR1 and GR2), and 2) a basal promoter/cyclic AMP response element (E/CRE) at about position -90, which binds the transcription factor CREB. A protein-protein interaction was observed in vitro between GR and CREB that might account for the role of the E/CRE in the glucocorticoid response of the PEPCK gene. PMID- 8449899 TI - Photosystem II reaction center particle from Spirodela stroma lamellae. AB - A Photosystem II (PSII) reaction center particle from the stroma lamellae of Spirodela oligorrhiza has been isolated. The stroma lamellar PSII reaction center contained the same proteins found in granal PSII reaction centers, namely D1, D2, and cytochrome b559; however, the cytochrome b559 content was half of that in the granal centers. The pigment composition, 77 K fluorescence emission, and excitation spectra of the stroma lamellar reaction centers were determined. Our results indicate a fully functional PSII particle in the stromal lamellae. PMID- 8449900 TI - A novel binding protein of the origin of the Escherichia coli chromosome. AB - The replication origin of Escherichia coli (oriC) was probed for specific binding proteins, using the gel shift assay. A 33-kDa protein that binds specifically to the right border of oriC, next to the rightmost of the binding sites of the initiator protein, DnaA, was identified and purified. The stoichiometry of protein to DNA is about 6 to 1. Around 5000 monomers of the protein, named Rob (right oriC binding), are present per cell. The rob gene has been located near 99.8 min on the E. coli map, cloned, and overexpressed. The total protein sequence reveals strong homologies to several regulatory proteins with which it shares the helix-turn-helix motif. PMID- 8449901 TI - Mechanism-based design of prolactin receptor antagonists. AB - The mechanism of action of two forms of the prolactin (PRL) receptor was studied using analogs of human growth hormone (hGH). At low concentrations (approximately 1 pM), hGH binds and stimulates proliferation of Nb2 cells containing the 391 residue PRL receptor as well as murine lymphoid FDC-P1 cells transfected with the 591-residue hPRL receptor. However, at high concentrations (approximately 70 microM) hGH inhibits proliferation of both these cell lines. Such a "bell-shaped" hormone response curve was observed for hGH stimulation of the hGH receptor (Fuh, G., Cunningham, B.C., Fukunaga, R., Nagata, S., Goeddel, D. V., and Wells, J.A. (1992) Science 256, 1677-1680) and is consistent with the sequential formation of an active hormone-(receptor)2 complex in which hGH binds through a first site (Site 1) to a first receptor and then through a second site (Site 2) to a second receptor. By analogy to hGH activation of the hGH receptor, we find that hGH variants that are mutated in Site 1 or Site 2 are greatly reduced as agonists. Similarly, only Site 2 mutants are potent antagonists of either hGH or hPRL stimulated cell proliferation. These and other data support the notion that hGH and hPRL activate the PRL receptor by sequential dimerization and provide a rational basis for the design of potent antagonists to the prolactin receptor. PMID- 8449902 TI - Characterization of the arcD arginine:ornithine exchanger of Pseudomonas aeruginosa. Localization in the cytoplasmic membrane and a topological model. AB - The arcDABC operon of Pseudomonas aeruginosa encodes the enzymes of the arginine deiminase pathway and is induced by oxygen limitation. The arcD gene specifies a 53-kDa protein with arginine: ornithine exchange activity. The ArcD protein of P. aeruginosa, like the LysI lysine transporter of Corynebacterium glutamicum, has 13 hydrophobic regions which could span the cytoplasmic membrane. Fusion of a Caa (colicin A) epitope to the N-terminal part of ArcD permitted the localization, by immunoblotting, of the hybrid protein in the inner membrane of P. aeruginosa. Fusion of PhoA (alkaline phosphatase) to the very C terminus of ArcD produced another hybrid protein, which exhibited PhoA activity. Both ArcD hybrid proteins retained arginine transport activity and served to support a topological model which proposes that the N terminus is oriented toward the cytoplasm and the C terminus faces the periplasm. Further ArcD-PhoA fusions were consistent with this model. When the Caa epitope was fused to a C-terminal ArcD fragment consisting of only 5 hydrophobic domains, the resulting hybrid protein could be recovered intact from the inner membrane, suggesting that the C-terminal part of ArcD contains sufficient information for insertion into the membrane. This study illustrates the utility of the Caa epitope to tag membrane proteins. PMID- 8449903 TI - Expression of the protein product of the prostaglandin synthase-2/TIS10 gene in mitogen-stimulated Swiss 3T3 cells. AB - TIS10/PGS-2 encodes a prostaglandin synthase (PGS) distinct from the previously described enzyme PGS-1 (EC 1.14.99.1). We have now generated antipeptide antisera, directed to an amino acid sequence unique to the murine TIS10/PGS-2 protein, which specifically recognize the TIS10/PGS-2 antigen. TIS10/PGS-2 protein was undetectable in quiescent Swiss 3T3 cells. The level of TIS10/PGS-2 protein peaked between 6 and 8 h following phorbol ester stimulation of cells, then declined to basal levels after 18-24 h. Synthesis of TIS10/PGS-2 protein was dramatically increased in the second hour following mitogen stimulation and remained elevated for several hours. The half-life of the TIS10/PGS-2 protein was 4 h. Immunofluorescence studies demonstrated a perinuclear and cytoplasmic localization of the TIS10/PGS-2 antigen. As expected, detection of induced TIS10/PGS-2 antigen was dependent on protein synthesis. Metabolically labeled TIS10/PGS-2 protein migrated as a 71/73-kDa doublet following immunoprecipitation. Dexamethasone blocked both the TPA- and serum-induced appearance of TIS10/PGS-2 antigen. These studies demonstrate the existence of a mitogen-inducible, glucocorticoid-inhibitable, immunologically distinct prostaglandin synthase protein. PMID- 8449904 TI - Transcriptional regulation of the pyruvate kinase erythroid-specific promoter. AB - Mammal pyruvate kinases are encoded by two genes. The L gene produces the erythroid (R-PK) or the hepatic (L-PK) isozymes by the alternative use of two promoters. We report the characterization of the cis- and trans-acting elements involved in the tissue-specific activity of the L gene erythroid promoter. A R-PK DNA fragment extending from -870 to +54 relative to the cap site confers erythroid specificity to a reporter gene. Within this region, we define a minimal promoter (-62 to +54) that displays erythroid-specific activity and contains two DNA binding sites. One, located at -50, binds members of the CCACC/Sp1 family and the other, located at -20, binds the erythroid factor GATA-1. Although the -20 GATA binding site (AGATAA) is also a potential TFIID binding site, it does not bind TFIID. Furthermore, the substitution of this GATA binding site by a canonical TFIID binding site suppresses the promoter activity. Mutations and deletions of both sites indicate that only the association of CCACC/Sp1 and GATA binding sites can drive efficient and tissue-specific expression of this R-PK minimal promoter. Finally, by co-transfection experiments, we study the elements involved in the hGATA-1 transactivation of the R-PK promoter in HeLa cells. PMID- 8449905 TI - Early light-inducible protein in pea is stable during light stress but is degraded during recovery at low light intensity. AB - The nuclear-encoded, thylakoid-bound early light-inducible protein (ELIP) reported to be related to the initial stages of chloroplast differentiation is synthesized in substantial amounts in leaves of mature plants exposed to light stress conditions (Adamska, I., Ohad, I., and Kloppstech, K. (1992b) Proc. Natl. Acad. Sci. U.S.A. 89, 2610-2613). Increase in ELIP content correlates with the photoinactivation of PSII, degradation of D1 protein, and changes in the level of pigments. Inhibition of phytoene desaturase and/or zeta-carotene desaturase during light stress drastically increases accumulation of the protein. ELIP mRNA is short-lived (t1/2 = 1 h). The thylakoid bound protein is stable in high light exposed leaves and is degraded only during recovery from light stress at low light intensity (40 microE/m2s). The lifetime of the protein during the recovery process increases with the extent of initial light stress condition. We propose that ELIP synthesis and degradation is related to the process of the plant response to light stress and recovery from photoinhibition. PMID- 8449906 TI - Isolation of an inhibitor selective for collagen-stimulated platelet aggregation from the soft tick Ornithodoros moubata. AB - Soluble extracts from the soft tick Ornithodoros moubata were found to inhibit collagen-, ADP-, and thrombin-stimulated platelet aggregation. One inhibitory component was purified to homogeneity by a combination of gel filtration, ion exchange, and reverse phase high pressure liquid chromatography. The purified activity, named moubatin, is a protein of molecular weight 17,000 and it inhibits the aggregation of washed human platelets stimulated by collagen with an IC50 of approximately 50 nM in the standard assay. At a concentration of moubatin that maximally inhibited collagen-stimulated platelet aggregation, no inhibition of aggregation initiated by other effectors, including arachidonic acid, thrombin, ristocetin, and the calcium ionophore A23187, was observed. Moubatin also inhibits collagen-dependent aggregation in plasma. At a higher concentration of moubatin (> 1 microM) it was also possible to demonstrate an inhibitory effect on the final extent of aggregation induced by a low concentration of ADP. Although moubatin selectively inhibits platelet activation by collagen, it has only a minimal effect on the adhesion of platelets to collagen. The amino acid sequences of peptides derived from proteolytic cleavage of moubatin suggest that moubatin is a unique protein, consistent with its novel functional activity. PMID- 8449907 TI - Cloning of the cDNA and expression of moubatin, an inhibitor of platelet aggregation. AB - Moubatin, a new type of specific inhibitor of collagen-induced platelet aggregation, has been isolated from the soft tick Ornithodoros moubata (Waxman, L., and Connolly, T. M. (1993) J. Biol. Chem. 268, 5445-5449). A polymerase chain reaction-generated hybridization probe, produced using primers based on moubatin protein sequence, identified phage containing the entire cDNA sequence of moubatin. Analysis of the predicted amino acid sequence yielded a mature protein of 156 amino acids with a putative prepeptide of 15 amino acids. Comparison of the sequence of moubatin to that of other proteins in the Swiss PROT data base revealed no significant homology. The cDNA sequence was cloned into the yeast expression vector pKH4 alpha 2, producing a biologically active protein which inhibited collagen-stimulated aggregation of washed human platelets with an IC50 of about 100 nM, which is similar to the potency of native tick moubatin. A concentration of recombinant moubatin that fully inhibited collagen-stimulated aggregation did not inhibit aggregation induced by a variety of other platelet agonists, again demonstrating comparable properties of the recombinant and native proteins. Moubatin did not inhibit platelet adhesion to collagen even at a concentration up to 16 times its IC50 for the inhibition of aggregation. This specificity for inhibiting collagen-stimulated aggregation and not adhesion to collagen indicates that moubatin is unique among the natural product inhibitors of collagen stimulation of platelets. Further examination of the mechanism of moubatin-mediated inhibition of collagen-stimulated aggregation revealed that 1-6 microM moubatin diminished the second phase of aggregation induced by ADP, inhibited aggregation in response to submaximal concentrations of the thromboxane A2 mimetic U46619, and competed for the binding of a thromboxane A2 receptor antagonist to platelet membranes. Therefore, at higher concentrations, moubatin may affect more than one aspect of platelet signal transduction including the thromboxane A2 receptor. The availability of recombinant moubatin will allow further investigation of its unique activities in vitro and in vivo. PMID- 8449908 TI - The bovine mannose 6-phosphate/insulin-like growth factor II receptor. The role of arginine residues in mannose 6-phosphate binding. AB - The extracytoplasmic region of the bovine cation-independent mannose 6 phosphate/insulin-like growth factor II receptor (M6P/IGF-II receptor) consists of 15 homologous repeating domains, each of which is approximately 147 residues in length. The receptor contains two high affinity mannose 6-phosphate (Man-6-P) binding sites and our recent studies (Westlund, B., Dahms, N. M., and Kornfeld, S. (1991) J. Biol. Chem. 266, 23233-23239) have localized these two binding sites to domains 1-3 and 7-11. To further define the location of the Man-6-P binding sites and to determine the role of specific arginine residues in Man-6-P binding, site-directed mutagenesis was utilized to create truncated soluble forms of the M6P/IGF-II receptor in conjunction with either conservative (Lys) or nonconservative (Ala) replacement of arginine residues. These mutants were expressed transiently in COS-1 cells and assayed for their ability to bind phosphomannosyl residues by affinity chromatography. Analysis of the ligand binding activity of carboxyl-terminal truncated forms of the receptor's extracytoplasmic region demonstrated that the second Man-6-P binding site is contained within domains 7-9. Substitution of Arg435 in domain 3 of the amino terminal binding site and Arg1334 in domain 9 of the second binding site results in a dramatic loss of ligand binding activity. However, substitutions at positions 435 and/or 1334 did not affect the secretion, glycosylation, or immunoreactivity of these truncated proteins. Taken together, these results indicate that Arg435 and Arg1334 are essential components of the M6P/IGF-II receptor's high affinity Man-6-P binding sites. PMID- 8449909 TI - Mutational analysis of active site residues of human adenosine deaminase. AB - Adenosine deaminase was overexpressed in a baculovirus system. The pure recombinant and native enzymes were identical in size, Zn2+ content, and activity. Five amino acids, in proximity to the active site, were replaced by mutagenesis. The altered enzymes were purified to homogeneity and compared to wild-type adenosine deaminase with respect to zinc content, enzymatic activity, and kinetic parameters. All but one of the alterations produced significant activity perturbations. Replacement of Cys262 produced a protein that retained at least 30-40% of wild-type activity. In contrast, replacements of His17, His214, His238, and Glu217 resulted in dramatic losses of enzyme activity. None of these mutants exhibited large variations in Km. The proteins produced from alterations of amino acids implicated in metal coordination were slightly activated by inclusion of Zn2+ throughout purification. These experiments confirm that in the active enzyme Zn2+ plays a critical role in catalysis, that a histidine or glutamate residue plays a mechanistic role in the hydrolytic deamination step, and that cysteine is not involved in the catalytic mechanism of adenosine deaminase. These data support the roles for these amino acid residues suggested from the x-ray structure of murine adenosine deaminase (Wilson, D. K., Rudolf, F. B., and Quicho, F. A. (1991) Science 252, 1278-1284). PMID- 8449910 TI - Cloning and analysis of two new isoforms of multifunctional Ca2+/calmodulin dependent protein kinase. Expression in multiple human tissues. AB - Multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase) is a mediator of calcium signals in diverse signaling pathways. In human lymphocytes and epithelial tissues, CaM kinase activates a chloride channel via a Ca(2+) dependent pathway which is preserved in cystic fibrosis. To characterize the CaM kinase present in these tissues we have cloned an isoform of this kinase from human T lymphocytes. We show the cDNA structure of two variants of this human CaM kinase, gamma B and gamma C, which are predicted to translate to 518 and 495 amino acids, respectively. Amino acid differences between these isoforms and the rat brain gamma isoform (which we refer to as gamma A) are localized to the variable domain. We used RNase protection of this variable region to reveal the level of expression of gamma B and gamma C CaM kinase mRNAs in nine human tissues and cell lines. When transfected into Jurkat T cells, the gamma B cDNA encoded a functional kinase which cosedimented on sucrose gradients with endogenous T cell CaM kinase activity and formed a large multimeric enzyme. The recombinant gamma B isoform displayed two phases of autophosphorylation characteristic of CaM kinases, including the phase which converts it to a partially Ca(2+)-independent species. Site-directed mutagenesis of the predicted autoinhibitory domain yielded a mutant which was approximately 37% active in the absence of Ca2+/calmodulin, confirming the region as critical for autoregulation, and suggesting this mutant as a tool for studying the role of CaM kinase in nonneuronal tissues. PMID- 8449911 TI - The membrane domain of a bacteriophage assembly protein. Transmembrane-directed proteolysis of a membrane-spanning fusion protein. AB - A tripartite fusion construct encoding the amino-terminal half of EcoRI endonuclease followed by amino acids 217-299 of the filamentous bacteriophage gene I protein (pI) attached to the enzymatic portion of alkaline phosphatase results in the production of two proteins. The larger protein, pIf, is the complete tripartite fusion protein while the smaller protein, pIf*, results from internal initiation of translation at pI methionine 241. Both pIf and pIf* span the Escherichia coli inner membrane via a 20-amino-acid hydrophobic stretch of pI with their amino termini in the cytoplasm and their carboxyl-terminal alkaline phosphatase domains in the periplasm. The alkaline phosphatase moiety of approximately 70% of pIf is released into the periplasm by in vivo proteolysis, but only about 10% of pIf* is cleaved. Neither DegP, OmpT, nor protease III are responsible for the cleavage in vivo, and leader peptidase is unable to cleave the fusion protein in vitro. Deletion and substitution analyses demonstrate that the degree of periplasmic cleavage depends on the sequence of the cytoplasmic domain of the fusion proteins. Possible mechanisms for this transmembrane directed cleavage event are compared to proposed models for signal transduction. PMID- 8449912 TI - The membrane domain of a bacteriophage assembly protein. Membrane insertion and growth inhibition. AB - The gene I protein (pI) of the f1 filamentous bacteriophage is a non-capsid protein that is required for the assembly of the bacteriophage. It spans the Escherichia coli inner membrane once with its amino terminus in the cytoplasm and its carboxyl-terminal portion in the periplasm. The presence of moderate amounts of this protein in the membrane results in rapid inhibition of cell growth, probably from a loss of membrane potential. Previous observations defined a 55 amino-acid sequence within pI required for its membrane insertion which includes a 20-residue hydrophobic stretch preceded by a 13-residue positively charged amphiphilic helix. To define the minimal sequence required for membrane translocation and for growth inhibition, a deletion analysis was performed on a tripartite fusion construct containing the 55-residue pI sequence flanked upstream by the amino-terminal portion of EcoRI endonuclease and downstream by the enzymatic portion of alkaline phosphatase. Only the 20-residue hydrophobic stretch immediately preceded by 1 arginine residue is required for membrane insertion of the fusion proteins. This region also sufficed to inhibit cell growth provided it contained protein domains exposed in both the cytoplasm and periplasm. It was not possible to separate the domains required for membrane insertion and cell growth inhibition. No requirement for the positively charged amphiphilic helix was detected either for membrane insertion or growth inhibition, suggesting that it plays a role in phage assembly and not membrane insertion. PMID- 8449913 TI - Purification, characterization, and kinetic analysis of a 2-oxoglutarate dependent dioxygenase involved in vindoline biosynthesis from Catharanthus roseus. AB - A 2-oxoglutarate-dependent dioxygenase (EC 1.14.11.11) which catalyzes the hydroxylation at position 4 of the indole alkaloid, desacetoxyvindoline has been purified to near homogeneity from Catharanthus roseus. The purification procedure combined conventional chromatographic methods and cosubstrate affinity chromatography on alpha-ketoglutarate-Sepharose. The specific activity of the 4 hydroxylase was enriched over 2000-fold compared to the crude homogenate with a recovery of 1.6%. The molecular mass of the native and denatured 4-hydroxylase was found to be 45 and 44.7 kDa, respectively, suggesting that the native enzyme is a monomer. Two-dimensional isoelectric focusing under denaturing conditions resolved the purified 4-hydroxylase into three charge isoforms of pI values 4.6, 4.7, and 4.8. The enzyme did not require most divalent cations, but inactive enzyme was reactivated in a time-dependent manner by incubation with ferrous ions. The mechanism of action of desacetoxyvindoline 4-hydroxylase was investigated. The results of substrate interaction kinetics and product inhibition studies suggest an Ordered Ter Ter mechanism where 2-oxoglutarate is the first substrate to bind followed by the binding of O2 and desacetoxyvindoline. The first product to be released was deacetylvindoline followed by CO2 and succinate, respectively. PMID- 8449914 TI - Purification of glutamine tRNA synthetase from Saccharomyces cerevisiae. A monomeric aminoacyl-tRNA synthetase with a large and dispensable NH2-terminal domain. AB - Glutamine tRNA synthetase from Saccharomyces cerevisiae has been purified to homogeneity and shown to be a monomer of 91 kDa. The size of the polypeptide agrees with that predicted from the previously reported translated DNA sequence. Mild tryptic digestion removes an amino-terminal domain and releases a fragment of 65 kDa which begins at Ser205. This tryptic fragment is similar in size and sequence to Escherichia coli glutamine tRNA synthetase and shows a modest increase from the full-length yeast enzyme in the Km values for glutamine and ATP and no difference in the kcat for aminoacylation or the Km for tRNA. Thus, the removal of the NH2-terminal domain appears to indirectly affect the ATP- and glutamine-binding sites in the nucleotide-binding fold domain to which the NH2 terminal domain is fused. A monoclonal antibody directed against the NH2-terminal domain of the full-length enzyme has little effect upon the aminoacylation activity. Therefore, over 200 amino acids of the NH2 terminus of the full-length enzyme form a domain that operationally has only a modest influence on the catalytic core of the protein. These studies reinforce the concept that eukaryotic synthetases have quasi-independent domains not found in their prokaryotic counterparts which may confer a function distinct from aminoacylation. PMID- 8449915 TI - Antineoplastic agent doxorubicin inhibits myogenic differentiation of C2 myoblasts. AB - Doxorubicin (Dox, adriamycin), an antineoplastic agent that can cause dilated cardiomyopathy, selectively inhibits muscle-specific gene expression in rodent cardiac muscle cells. This study shows that Dox treatment of proliferating C2 myoblasts, an established cell line from mouse skeletal muscle, completely prevents both fusion and accumulation of muscle-specific gene transcripts without significantly altering non-muscle gene transcripts. When added to high density cultures, Dox only blocked myotube formation but did not inhibit induction of muscle-specific genes. Transient transfection into C2 myoblasts showed that the transcriptional expression of chloramphenicol acetyltransferase reporter plasmids regulated by either the cardiac alpha-actin promoter or the muscle creatine kinase enhancer, but not with a viral or beta-actin promoter, was significantly diminished by Dox in a dose-dependent manner. Moreover, exposure of C2 myoblasts to Dox had a profound effect on the expression of regulatory genes critical to the myogenic differentiation program; mRNAs for MyoD and myogenin were dramatically reduced and Id mRNA was concomitantly increased. In addition, there was diminished DNA binding activity of the muscle-specific transcription factor, MEF-2. These results suggest that Dox inhibits myogenesis by preventing muscle specific gene expression, possibly through affecting the myogenic programs controlled by muscle-specific transcription factors. PMID- 8449916 TI - Protein kinase C activation without membrane contact in platelets stimulated by bryostatin. AB - The tumor promoter phorbol myristate acetate (PMA) directly activates protein kinase C (PKC) and, in human platelets, induces aggregation, release of granular contents, mobilization of intracellular Ca2+ as detected by the photoprotein aequorin, and phosphorylation of the 47-kDa substrate (p47) of PKC. Whether PKC activation by PMA or other agonists requires translocation of PKC from the cytoplasm to the lipids of the platelet surface membrane, however, is not known. Bryostatin-1, a macrocyclic lactone that binds to PKC at or near the PMA-binding site and thus blocks PMA's proliferative effects, induced concentration-dependent p47 phosphorylation, platelet aggregation, release of dense granule contents, and a rise in cytoplasmic Ca2+ (ED50 = 2.0 nM) in intact aequorin-loaded platelets. Neither alpha-, beta-, delta-, or zeta-PKC isozymes translocated to the plasma membrane following bryostatin-1, although translocation of both alpha- and beta PKC isozymes was seen in PMA-stimulated platelets. In a cell-free assay, bryostatin-1 activated PKC purified from platelets if the membrane-derived lipid phosphatidyl serine was present; however, if 12(S)-hydroxy-5,8,10,14 eicosatetraenoic acid or arachidonic acid, two lipid products formed in the cytoplasm of activated platelets, were present, no membrane-derived lipids were required for bryostatin-induced PKC activation. Thus, phosphorylation of PKC substrates and associated functional changes do not require isozyme translocation to the surface membrane, even when these events are induced by a direct activator of PKC. PMID- 8449917 TI - The tissue plasminogen activator finger domain confers fibrin-dependent enhancement of catalytic activity to single-chain urokinase-type plasminogen activator. AB - To determine whether the fibrin-binding domains of tissue plasminogen activator (tPA) can confer enhanced catalytic activity to single-chain urokinase-type plasminogen activator (scuPA), we constructed, expressed, and characterized the kinetics of five recombinant tPA/scuPA hybrid molecules. The hybrid molecules are: 1) tPA3-50 (tPA finger)/scuPA138-411, 2) tPA177-256 (tPA kringle2)/scuPA140 411 (scuPA catalytic), 3) tPA3-50/tPA177-256/scuPA140-411, 4) scuPA1-47 (scuPA growth factor)/tPA177-256/scuPA140-411, and 5) scuPA1-138 (scuPA growth factor and kringle)tPA127-256/scuPA139-411. The amidolytic activity of all hybrids was comparable, as were the kinetics for conversion from single-chain to two-chain plasminogen activator. We found that 1) the lag time prior to achieving maximal velocity among these hybrids varied, 2) hybrids 2, 3, 4, and 5 were 2-134-fold more potent (by kcat/Km) than hybrid 1, and 3) those hybrid proteins containing the tPA finger domain (hybrids 1 and 3) gave a 2-fold increase in catalytic efficiency in the presence of DESAFIB (reptilase-digested fibrinogen). These kinetic differences are likely mediated by changes in the tertiary structure of the scuPA catalytic domain resulting from interactions between catalytic and noncatalytic domains in the presence of fibrin. PMID- 8449918 TI - Expression of integrin alpha 1 beta 1 is regulated by nerve growth factor and dexamethasone in PC12 cells. Functional consequences for adhesion and neurite outgrowth. AB - PC12 cells respond to nerve growth factor by differentiating into sympathetic neuron-like cells that employ the integrin alpha 1 beta 1 to attach to, and extend neurites on, substrata coated with collagen or laminin. In one PC12 subline, PC12i, prolonged treatment with nerve growth factor results in a marked increase in synthesis of alpha 1 subunits and in the level of alpha 1 mRNA, with a corresponding increase in alpha 1 beta 1 expressed on the cell surface. These changes are accompanied by substantial increases in initial cell attachment to collagen and in the fraction of neurite-bearing cells and average neurite length. Integrin beta 1-subunits are constitutively expressed, so that alpha 1 synthesis controls the amount of alpha 1 beta 1 heterodimer expressed on PC12i cells. Acidic fibroblast growth factor also induces alpha 1 beta 1 in PC12i cells, with consequent enhancement of neurite outgrowth; treatment with epidermal growth factor or dibutyryl cyclic AMP does not have these effects. Another subline, PC12c, expresses high levels of alpha 1 mRNA and alpha 1 protein constitutively. With or without nerve growth factor pretreatment, these cells adhere well to collagen and a majority extend neurites when replated in the presence of nerve growth factor. Dexamethasone treatment of PC12c cells reduces expression of alpha 1 mRNA and alpha 1 protein, with consequent reduction in attachment to collagen. In both sublines, then, there is a direct relationship between the level of a specific matrix receptor and cell-matrix adhesion. Moreover, our results suggest that induced expression of this matrix receptor is an essential aspect of the regulation of neurite extension by nerve growth factor in PC12i cells. PMID- 8449919 TI - The p46 subunit of eukaryotic initiation factor (eIF)-4F exchanges with eIF-4A. AB - The p46 subunit of eukaryotic initiation factor (eIF)-4F purified from rabbit reticulocyte lysate has previously been found to be composed of eIF-4AI and eIF 4AII in a 4:1 ratio, respectively, whereas the free form of rabbit eIF-4A is composed solely of eIF-4AI. Using sucrose gradient centrifugation and an m7GTP Sepharose 4B assay, it was shown that eIF-4A exchanges with the p46 subunit of eIF-4F. Incubation of [14C]eIF-4A and eIF-4F resulted in the incorporation of [14C] eIF-4A into the eIF-4F complex. Conversely, the [14C] p46 subunit of [14C]eIF-4F was shown to dissociate from the [14C]eIF-4F complex in the presence of eIF-4A, presumably due to the incorporation of unlabeled eIF-4A. Similar experiments were conducted in which 14C-labeled initiation factors were incubated with rabbit reticulocyte lysate. When [14C]eIF-4A was incubated with lysate, [14C]eIF-4A became incorporated into the eIF-4F complex present in the lysate. Additionally, when [14C]eIF-4F was incubated with lysate, the [14C]p46 subunit of [14C]eIF-4F dissociated from the [14C]eIF-4F complex, most likely due to the exchange of unlabeled eIF-4A (present in the lysate) with the [14C]p46 subunit. The exchange of mouse eIF-4AI and eIF-4AII expressed in Escherichia coli was also investigated in the presence of eIF-4F and rabbit reticulocyte lysate. Both the sucrose gradient experiments and m7GTP-Sepharose 4B assays demonstrated that the [14C]p46 subunit of [14C]eIF-4F was displaced in the presence of eIF-4AI or eIF 4AII and that mouse [14C]eIF-4AI or [14C]eIF-4AII became incorporated into the eIF-4F complex in the same manner as rabbit reticulocyte eIF-4A. PMID- 8449920 TI - A chimeric alpha-glucan phosphorylase of plant type L and H isozymes. Functional role of 78-residue insertion in type L isozyme. AB - Higher plant tissues such as potato tuber and leaf contain two alpha-glucan phosphorylase isozymes designated types L and H. Although the sequences of the two isozymes are highly conserved except for a 78-residue insertion found uniquely in the type L isozyme, they differ strikingly in affinities for substrates. To examine whether the insertion in the type L isozyme plays a role in enzymic functions, particularly in substrate specificities, we have constructed a chimeric enzyme, in which a 189-residue sequence of the type L isozyme including the insertion and its flanking regions is replaced by the corresponding sequence (112 residues) of the type H isozyme lacking the insertion. The gene for the chimeric enzyme as well as the cDNA for the type L isozyme were expressed at a low temperature in Escherichia coli cells under the control of the strong T7 RNA polymerase promoter. The purified chimeric phosphorylase was five times less active than the parent type L isozyme, but its affinity for glycogen was much higher than that of the type L isozyme and only slightly lower than that of the type H isozyme. The Michaelis constants of the chimeric enzyme for small oligosaccharides were comparable with those of the type L isozyme. These results provide evidence for the role of the 78-residue insertion in the type L isozyme, lowering the affinity of the enzyme for large, branched substrates probably through steric hindrance. It is also assumed that the corresponding region in the type H isozyme contains a high affinity site like the glycogen storage site occurring in the animal enzyme. PMID- 8449921 TI - Basic fibroblast growth factor inhibits type I collagen gene expression in osteoblastic MC3T3-E1 cells. AB - We examined the effect of basic fibroblast growth factor (bFGF) on alpha 1(I) procollagen mRNA levels, alpha 1(I) collagen gene transcription, and alpha 1(I) collagen promoter activity in osteoblastic MC3T3-E1 cells. Cells were stably transfected with ColCAT 3.6, containing 3521 base pairs of alpha 1(I) collagen promoter DNA, fused to the CAT reporter gene, or an upstream deletion mutant of ColCAT 3.6 designated ColCAT 2.3. After 48 h, bFGF (0.1-10 nM) inhibited the incorporation of [3H]proline into collagenase-digestible protein (CDP). Indomethacin did not alter the inhibitory effect of bFGF on CDP labeling. Aphidicolin, an inhibitor of DNA synthesis, did not block the inhibitory effect of bFGF on CDP. bFGF (1-10 nM) decreased alpha 1(I) procollagen mRNA levels, with maximal inhibition, nearly 99% of control, caused by 10 nM bFGF. After 48 h, bFGF (1 nM) reduced alpha 1(I) procollagen gene transcription by about 92%. ColCAT 3.6 activity was inhibited with 0.1-10 nM bFGF and was maximally repressed by about 83% with 10 nM bFGF. In contrast, bFGF (1 and 10 nM) caused a stimulation of ColCAT 2.3 activity. These data show that bFGF inhibits collagen synthesis by a transcriptional mechanism and the alpha 1(I) collagen promoter contains DNA sequences which mediate bFGF inhibition of type I collagen gene expression in bone. PMID- 8449922 TI - DNA processing during entry in transformation of Streptococcus pneumoniae. AB - The current model for processing DNA during entry in the transformation of Streptococcus pneumoniae is that following double-strand cleavage of DNA bound at the cell surface, uptake of one strand proceeds linearly from a newly formed 3' end with simultaneous degradation of the opposite strand. Two important predictions of this model have been tested in the work reported here: first that the polarity of DNA degradation is the opposite of that for entry, and second that the rate of DNA degradation is (at least) equal to the rate of entry. The processing of DNA during entry was investigated using donor molecules constructed in vitro and labeled in one strand only. With uniformly labeled donor molecules, an amount of label equivalent to that taken up by the cells was recovered in acid soluble form in the transformation medium. Experiments with 3'- or 5'-end-labeled molecules revealed that whereas essentially all of the 3'-end label was susceptible to degradation, most 5'-end label was resistant. Kinetic analysis of both entry and degradation revealed very similar rates for these processes, about 100 nucleotides s-1 at 31 degrees C, suggesting that they occur concomitantly. Entry and degradation appear to proceed with opposite polarity, 3'-->5' for entry and 5'-->3' for degradation. A prediction of the entry model, that a single strand interruption would inhibit the uptake of DNA sequences located 5' to the nick, was confirmed experimentally. Therefore, we suggest that an intact sugar phosphate backbone is required by the entry machinery for continuous uptake. PMID- 8449923 TI - Characterization of the nuclear binding sites of oligodeoxyribonucleotides and their analogs. AB - The intracellular fate of antisense oligodeoxyribonucleotide (oligomers) is poorly understood. Recent observations strongly suggest that after endocytosis and escape from the endocytic compartments, oligomers accumulate in the nuclei of eukaryotic cells by simple diffusion. Isolated nuclei were used to determine the number of these nuclear binding sites and their affinity for phosphodiester, phosphorothioate, and methyl-phosphonate oligomers. These cell-free assays were correlated with intact cell microinjection experiments. Great differences have been observed between these analogs. These data are helpful in understanding the fate of oligomers and the mechanism of their action and could be helpful for a more rational design of antisense molecules. PMID- 8449924 TI - Sequence and expression of the gene encoding the corrinoid/iron-sulfur protein from Clostridium thermoaceticum and reconstitution of the recombinant protein to full activity. AB - The corrinoid/iron-sulfur protein (C/Fe-SP) from Clostridium thermoaceticum acts as a methyl group carrier in the anaerobic acetyl-CoA pathway of CO and CO2 fixation. Consisting of a small (approximately 33 kDa) and a large (approximately 55 kDa) subunit, the C/Fe-SP contains 1 mol of cobalt in a corrinoid cofactor and 1 mol of [4Fe-4S]2+/1+ cluster/mol of alpha beta dimer. Cobalt is the site of methylation, and the [4Fe-4S] center appears to serve an electron transfer function. The genes encoding both subunits have been cloned previously and are located within a gene cluster that includes other genes required for CO2 fixation by anaerobic bacteria. When the genes encoding the C/Fe-SP were expressed in Escherichia coli, the protein was found to be inactive. We report the amino acid sequences of the large and small subunits of the C/Fe-SP based on the DNA sequences of the cloned genes. The [4Fe-4S] cluster was found to be located in the large subunit. Although the primary structural lattice for cobamide binding resides in the small subunit, both subunits are required for formation of a stable cobamide-binding protein. Based on sequence comparisons with other [4Fe 4S]-containing proteins, 3 of the 4 cysteine residues that serve as ligands to the iron sites in the cluster have been located. The two subunits were independently overexpressed in E. coli to a level of 30-50% of cell protein; however, the resulting protein was inactive, lacked stoichiometric amounts of Fe S cluster, and lacked cobamide. By combining the recombinant subunits, unfolding them with urea, and refolding in the presence of cobamide, iron, and inorganic sulfide, the resulting C/Fe-SP was found to contain stoichiometric amounts of cobamide and [4Fe-4S] cluster and had spectroscopic and enzymatic properties similar to those of the native protein. We expect that the methods developed here may be used for heterologous overexpression and reconstitution of other complex metalloenzymes. The C/Fe-SP was found to utilize with equal efficiency either vitamin B12 or the natural cofactor 5-methoxybenzimidazolylcobamide as a methyl carrier. PMID- 8449925 TI - Purification and characterization of the prohormone convertase PC1(PC3). AB - The prohormone convertases PC1 (also known as PC3) and PC2 have been implicated in the biosynthesis of several polypeptide hormones and neuropeptides. In order to understand the regulation and the cell biology of prohormone cleavage, we have purified recombinant mouse PC1 from the conditioned medium of overexpressing Chinese hamster ovary cells. Recombinant PC1 was found to be an 87-kDa calcium dependent proteinase with an inhibitor profile similar to that of Kex2 and furin. However, unlike furin, the optimum pH for PC1 activity is between pH 5.5 and 6.5. Like furin, the enzyme is activated at millimolar rather than at micromolar concentrations of calcium. Chinese hamster ovary/PC1 cells secrete the mature form of PC1, converted by a proteolytic cleavage on the carboxyl side of the RSKR motif located at residues 80-83. This conversion occurs very early in biosynthesis, suggesting that, like Kex2 and furin, PC1 may be activated autocatalytically. Specificity studies with fluorogenic substrates showed that the enzyme prefers substrates with an arginine 4 amino acids amino-terminal to the cleavage site; synthetic tripeptide substrates containing only pairs of basic amino acids are not well cleaved. However, the neuropeptide precursor proenkephalin is cleaved by PC1 to yield a peptide B-sized peptide; since peptide B represents the naturally occurring carboxyl-terminal fragment of proenkephalin, these data suggest a role for PC1 in the processing of this precursor. PMID- 8449926 TI - Penicillin-binding protein 1B from Escherichia coli contains a membrane association site in addition to its transmembrane anchor. AB - A working structural model of penicillin-binding protein 1B (PBP 1B) from Escherichia coli derived from previous data consists of a highly charged aminoterminal cytoplasmic tail, a 23-amino-acid hydrophobic transmembrane anchor, and a 758-amino-acid periplasmic domain. Using an engineered thrombin cleavage site, we have investigated the solubility properties of the periplasmic domain of PBP 1B. Twelve amino acids, comprised of the consensus thrombin cleavage site (LVPR decreases GS) and flanking glycine residues, were inserted into PBP 1B just past its putative transmembrane segment. To aid in purification, a hexa-histidine tag was also inserted at its amino terminus, and the engineered protein (PBP 1B GT/H6) was purified and characterized. Inclusion of the thrombin cleavage site had no effect on the protein's intrinsic tryptophan fluorescence and affinity for [14C]penicillin G, indicating that the protein structure was not significantly perturbed. PBP 1B-GT/H6 was readily cleaved by thrombin at low thrombin/protein ratios to a protein with properties consistent with the removal of its cytoplasmic tail and transmembrane regions. Cleavage of the protein was dependent upon the presence of the thrombin cleavage site, and the thrombin-cleaved protein (PBP 1Bper) displayed an identical affinity for [14C] penicillin G binding as wild-type PBP 1B and uncleaved PBP 1B-GT/H6. [14C]Penicillin G-labeled PBP 1Bper eluted from a gel filtration column in the presence but not in the absence of 0.7% 3-[(3-cholamidopropyl)dimethylammonio]-1- propanesulfonic acid, and PBP 1Bper was found entirely in the membrane fraction of a thrombin digest of membranes containing overproduced PBP 1B-GT/H6. To further characterize this unusual solubility behavior, purified PBP 1Bper was reconstituted into lipid vesicles, which were then floated on a sucrose gradient. Floated vesicles contained > 95% of total 125I-penicillin V binding, indicating that PBP 1Bper directly associates with lipid membranes. These results strongly suggest that the periplasmic domain of PBP 1B associates with membranes independent of its amino terminal transmembrane region. PMID- 8449927 TI - Further characterization of the alpha-actinin-actin interface and comparison with filamin-binding sites on actin. AB - The interaction between alpha-actinin and actin was further characterized using natural and synthetic peptides of actin together with anti-actin antibodies of known specificity. We demonstrated that two alpha-actinin binding sequences on actin are located within residues 112-125 and 360-372. Each peptide was shown to directly bind alpha-actinin and was able to dissociate the alpha-actinin-actin complex using solid phase binding assays and cosedimentation experiments. Taking into account the three-dimensional structure of actin (Kabsch, W., Mannherz, H. G., Suck, D., Pai, E. F., and Holmes, K. C. (1990) Nature 347, 37-44), we postulate that these two segments, proximal in the actin structure, are part of the same site. In addition, we compared these two segments with those recently found for filamin (Mejean, C., Lebart, M. C., Boyer, M., Roustan, C., and Benyamin, Y. (1992) Eur. J. Biochem. 209, 555-562), Egan, S., Stewart, M., Stossel, T. P., Kwiatkowski, D. J., and Hartwig, J. H. (1990) J. Cell Biol. 111, 1089-1105), and concluded that the two actin-binding proteins interact with closely spaced or overlapping but not identical sequences of actin subdomain 1. PMID- 8449928 TI - Purification and characterization of lysosomal H(+)-ATPase. An anion-sensitive v type H(+)-ATPase from rat liver lysosomes. AB - Lysosomal H(+)-ATPase was purified to homogeneity from rat liver lysosomes. It is a bafilomycin A1-sensitive Mg(2+)-ATPase, which reacts with antibodies against the 16- and 70-kDa subunits of vacuolar H(+)-ATPase (Nezu, J., Motojima, K., Tamura, H., and Ohkuma, S. (1992) J. Biochem. (Tokyo) 112, 212-219), and has been separated from both the N-ethylmaleimide (NEM)-sensitive/bafilomycin A1 insensitive Mg(2+)-ATPase (ATPase I) and the NEM-insensitive Mg2+/Ca(2+)-ATPase (ATPase II) (Hayashi, H., Arai, K., Sato, O., Shimaya, A., Sai, Y., and Ohkuma, S. (1992) Chem. Pharm. Bull. 40, 2783-2786). The purified enzyme had the subunit structure of vacuolar H(+)-ATPase, consisting of 110-, 70-, 56-, 42-, 39-, 34-, (32-,) and 16-kDa proteins. It had optimal activity at a pH of 7.0-8.0, with an apparently single Km value for ATP of 95 microM. It hydrolyzed ATP > or = dATP >> GTP, ITP >> UTP, but not CTP, and was inhibited by ADP. It demonstrated divalent cation specificity in the order of Mg2+, Mn2+ > Fe2+, Co2+ > Ca2+. Among various anions, Cl-, Br-, and F- activated ATPase activity, whereas NO3- inhibited activity. It was inhibited not only by bafilomycin A1 but also by NEM, 7-chloro-4 nitrobenzo-2-oxa-1,3-diazole, quercetin, and dicyclohexylcarbodi-imide. The purified enzyme was incorporated into proteoliposomes where its proton pump activity was reconstituted. This suggested that the isolated enzyme maintains its H+ translocation activity. These findings suggest that the isolated enzyme is an anion-sensitive vacuolar type H(+)-ATPase that functions as a lysosomal proton pump. PMID- 8449929 TI - Cloning and characterization of human colon glyoxalase-I. AB - Glyoxalase-I cDNA clones were isolated from a human colon cDNA library using polyclonal antibodies raised against the protein purified from human colon tissue. Positive clones were purified, subcloned, and their nucleotide sequence determined. The glyoxalase-I cDNA encodes a 184-amino acid protein with a predicted molecular weight of 20,774, corresponding to the monomeric subunit weight of the purified protein from human colon glyoxalase-I. The human enzyme showed 51% homology at the nucleotide level and 42% at the amino acid level with bacterial glyoxalase-I. Transfection of COS-1 cells with the 622-base pair cDNA containing the entire coding region cloned into a pMT2 vector produced an immunoreactive protein and an approximate 180-fold increase in glyoxalase-I enzyme activity as determined with methylglyoxal as a substrate. Transfection of a truncated cDNA lacking 94 base pairs of the 5'-coding sequence also produced an approximately 15-kDa immunoreactive protein, but with no detectable increase in enzyme activity. Northern analysis of the RNA showed an approximately 12-fold increase of the 2.2-kilobase glyoxalase-I transcript in carcinoma when compared to normal colon tissue from the same patient. Examination of colon carcinomas for the amplification of the glyoxalase-I gene by Southern blot analysis revealed no change in gene copy number. These results suggest induction of the glyoxalase-I gene expression in colon carcinomas. PMID- 8449930 TI - Transfected m2 muscarinic acetylcholine receptors couple to G alpha i2 and G alpha i3 in Chinese hamster ovary cells. Activation and desensitization of the phospholipase C signaling pathway. AB - Muscarinic acetylcholine receptor subtypes (m1-m5) differentially regulate phosphoinositide-specific phospholipase (PLC) through the activation of distinct guanine nucleotide-binding (G) proteins which can be distinguished on the basis of their sensitivity to inhibition by pertussis toxin (PTX). In transfected Chinese hamster ovary cells, the m2 receptor subtype regulates the stimulation of PLC and inhibition of adenylyl cyclase (AC) through PTX-sensitive G proteins. In this study, we utilized the ability of cholera toxin (CTX) to ADP-ribosylate PTX sensitive alpha subunits as part of the ternary complex formed by heterotrimeric G proteins and agonist-bound receptors to detect and characterize the interactions between transfected m2 receptors and endogenous G proteins in Chinese hamster ovary cells. In membranes derived from cells expressing the m2, but not the m3 receptor, the cholinergic agonist carbachol stimulated CTX modification of a 40-kDa species (G alpha 40). Importantly, similar carbachol dose dependence values and PTX dose sensitivities were observed for m2 receptor mediated PLC signaling and G alpha 40-CTX modification. High resolution urea-SDS polyacrylamide gel electrophoresis analysis revealed that G alpha i2 (40 kDa) and G alpha i3 (41 kDa) were components of the G alpha 40 identified by m2 receptor dependent CTX modification. Furthermore, the sensitivities of G alpha i2 and G alpha i3 to PTX modification were determined to be the same as those for PTX inhibition of G alpha 40 labeling by CTX and m2 receptor-mediated PLC signaling. Similarly, agonist-induced desensitization of m2 receptor-G protein signaling required doses of agonist associated with stimulation of PLC. Desensitization involved receptor sequestration and down-regulation of G alpha i3; however, only the reduction of G alpha i3 required prior activation PLC signaling. Finally, desensitization of m2-G protein coupling could be partially mimicked by treatment with thapsigargin, an inducer of intracellular Ca2+ release, without altering the number of cell surface receptors or G protein levels. These results demonstrate that m2 receptors couple to both G alpha i2 and G alpha i3 in vivo and that this interaction is integral to both positive and negative regulatory pathways leading to activation of PLC and desensitization of receptor signaling. PMID- 8449931 TI - Cloning, sequencing, and expression of a cDNA encoding beta-alanine synthase from rat liver. AB - A cDNA for beta-alanine synthase from rat liver has been isolated, sequenced, and characterized. beta-Alanine synthase clones were isolated from rat liver cDNA libraries in lambda gt11, using affinity-purified polyclonal antibodies against beta-alanine synthase protein. beta-Alanine synthase protein was not expressed with equal efficiency by all clones. One of the expressed fusion proteins has normal specific enzyme activity, and a second has reduced specific activity. Both clones were completely sequenced and yielded identical DNA sequence, except that one clone contained an additional 36 bases of 5' sequence. The various clones of this cDNA code for an EcoRI insert of 1.5 +/- 0.1 kb, and the open reading frame corresponds to a protein of 393 amino acids (M(r) = 44,042), in good agreement with the M(r) of approximately 42,000 for the native enzyme on SDS-gel electrophoresis. An 11-amino acid sequence was obtained from a tryptic peptide of native beta-alanine synthase; 11 codons for these same amino acids were found at the expected site in the sequenced cDNA, and confirm the open reading frame of the beta-alanine synthase cDNA. Chemical analysis of the native enzyme shows 2 zinc atoms per subunit, and the sequence of beta-alanine synthase contains 2 putative zinc-binding site motifs. Comparison of amino acid sequence, deduced from the cDNA sequence, to sequences in the protein data base showed that it is a unique sequence and that it has about 20% identity to aspartate carbamoyltransferase, ornithine carbamoyltransferase, urease, and leucine aminopeptidase; enzymes that bind comparable ligands or have a similar mechanism. PMID- 8449932 TI - Human casein kinase II. The subunit alpha protein activates transcription of the subunit beta gene. AB - Casein kinase II (CKII), an ubiquitous serine/threonine protein kinase in control of a variety of crucial cellular functions, is composed of catalytic subunits (alpha and alpha') and regulatory subunits (beta). The adjusted activity of CKII is determined by the actual conformational state of CKII beta and the stoichiometry of the CKII subunits. Thus, the expression control of CKII beta is of particular concern. Carrying out gel shifts and footprints with affinity purified proteins and cellular extracts in combination with mutational analysis we find that aside NF1 and Sp1, two out of the many factors predicted to bind to the upstream promoter region of the human CKII beta gene (Voss, H., Wirkner, U., Jakobi, R., Hewitt, N. A., Schwager, C., Zimmermann, J., Ansorge, W., and Pyerin, W. (1991) J. Biol. Chem. 266, 13706-13711), CKII alpha protein is able to complex with the CKII beta gene promoter. The complex of CKII beta-DNA/CKII alpha-protein is shown to occur within the 170-239-base pair (bp) segment upstream of the first transcription start site of the gene. The DNA motif contains, in a distance of 44 bp, two GC-rich boxes, 5'-GGGGCCC and 5'-CCCCTGGGC, and represents a novel cis acting element; the binding of the CKII alpha protein activates the CKII beta gene promoter. This is manifested by driving the expression of the indicator gene luciferase or of CKII alpha-cDNA in HeLa cells. The binding of the CKII alpha protein is inhibited due to CKII beta protein addition or by mimicking the corresponding situation in vivo by overexpression of the CKII subunits. The data suggest that cells may maintain a certain CKII subunit stoichiometry via transcriptional control; excess of nuclear CKII alpha protein could activate the CKII beta gene transcription causing CKII beta protein to increase which, in turn, could feed back to abolish the action of CKII alpha at the CKII beta gene promoter. PMID- 8449933 TI - Ligand binding and conformation change in the dimeric hemoglobin of the clam Scapharca inaequivalvis. AB - The reaction with carbon monoxide of the cooperative dimeric hemoglobin from Scapharca inaequivalvis has been examined by flash photolysis. In the nanosecond time range, geminate rebinding of 5% of dissociated CO occurs with a rate constant of 1.4 x 10(7) s-1. There is a change in absorbance of deoxyhemoglobin following photolysis at a rate of 1.2 x 10(6) s-1, consistent with a shift in the position of the Soret band to longer wavelengths. The amplitude of the change is proportional to the population of deoxydimer. In much of the Soret region this change is greater than the absorbance excursion associated with geminate recombination. There is at least one other slower change associated with the singly liganded species. Geminate rebinding of NO has components of 50, 8, and 0.035 ns-1, accounting for 75%, 25%, and less than 1% of the total reaction observed after a 35-ps photolysis flash. Simulation of diffusion of NO by molecular dynamics shows the ligands moving from the heme pocket to a subsidiary space between the edge of the heme and the surface of the protein. PMID- 8449934 TI - Heme-heme interactions in a homodimeric cooperative hemoglobin. Evidence from transient Raman scattering. AB - The comparison of the resonance Raman spectrum of the deoxy dimeric hemoglobin (HbI) from the Arcid clam, Scapharca inaequivalvis, to its CO photoproduct at 10 ns reveals several significant differences in the low frequency vibrational modes including those involving motions of the peripheral substituents on the heme such as the propionates. This finding reflects the involvement of the propionates in a hydrogen bonding network which connects the two heme groups across the subunit interface and is sensitive to ligand binding. A frequency difference in the iron histidine stretching mode of 6 cm-1 in this invertebrate hemoglobin is substantially smaller than that detected in tetrameric vertebrate hemoglobins under similar conditions. Time evolution studies of the vibrational modes from the photoproduct demonstrate that the transient form relaxes to the deoxy structure concertedly with a half-life of 1 microseconds, the time scale in which tertiary relaxations of tetrameric hemoglobins occur. These data establish that the tertiary and quaternary structural changes take place on the same time scale and confirm a mechanism of cooperativity involving direct interaction between the two heme groups through the peripheral substituents. This direct structural communication provides a very tight linkage between the heme groups prohibiting modulation of the oxygen affinity by factors in the physiological milieu. PMID- 8449935 TI - The mitogenic effect of thrombin in vascular smooth muscle cells is largely due to basic fibroblast growth factor. AB - Mitogenesis induced by most polypeptide growth factors is mediated by either G protein- or tyrosine kinase-linked receptor pathways. Thrombin, a potent mitogen for vascular smooth muscle cells, activates a G-protein-coupled receptor but also requires tyrosine kinase activity for its mitogenic effect (Weiss, R. H., and Nuccitelli, R. (1992) J. Biol. Chem. 267, 5608-5613). Since this growth factor elicits a synergistic effect on DNA synthesis when applied to cells concurrently with basic fibroblast growth factor (bFGF), we suspected that the two growth factors have points of convergence in their signaling pathways. We now show that when 1 unit/ml thrombin is removed after an incubation period of from 4 h to 15 min prior to 15 ng/ml bFGF addition, its synergistic effect with bFGF on mitogenesis in vascular smooth muscle cells is preserved. Furthermore, appearance of bFGF in the cellular lysate is maximal 1 h after the addition of 1 unit/ml thrombin. While monoclonal antibody to bFGF inhibits thrombin's mitogenic effect by 63% at 30 micrograms/ml, it lacks an inhibitory effect on platelet-derived growth factor-BB-induced mitogenesis. The inhibitory effect of bFGF antibody on thrombin's growth is completely reversed by the addition of bFGF. These data demonstrate that the presence of bFGF is essential for thrombin to exert its full mitogenic effect in vascular smooth muscle cells, providing an example of a system where a tyrosine kinase-linked growth factor receptor system can act as an essential intermediary in the mitogenic signaling pathway of a G-protein-coupled receptor. PMID- 8449936 TI - Functional characterization of flavin-containing monooxygenase 1B1 expressed in Saccharomyces cerevisiae and Escherichia coli and analysis of proposed FAD- and membrane-binding domains. AB - A cDNA encoding the flavin-containing monooxygenase of rabbit lung (FMO 1B1) was expressed in yeast and Escherichia coli and the recombinant enzymes characterized. A high copy, isopropyl-1-thio-beta-D-galactopyranoside (IPTG) inducible E. coli expression vector, pKKHC, was used for expression in E. coli strain JM109, and a galactose-inducible vector, YEp53, was used for expression in yeast strain 334. Following transcriptional induction with IPTG or galactose, subcellular fractions were prepared and analyzed immunochemically and catalytically. Antibodies to rabbit FMO 1B1 were used to detect the recombinant proteins in the 100,000 x g pellet prepared from the 10,000 x g supernatant fraction of yeast homogenates and the 2,000 x g supernatant fraction of E. coli homogenates. No FMO 1B1 was detected in cytosol. Mobilities of the recombinant proteins in SDS-polyacrylamide gel electrophoresis appeared identical to that of the native microsomal enzyme. Catalytic similarity to the native FMO 1B1 was demonstrated by the ability of the expressed enzymes to metabolize methimazole, thiourea, dimethylaniline, and cysteamine, but not chlorpromazine or imipramine. In addition, the recombinant enzymes exhibited a number of the unique physical properties associated with FMO 1B1, including stability to elevated temperature and activation by sodium cholate and magnesium chloride. Based on the specific content of FAD, the level of expression was estimated to be approximately 2% of the total protein in the E. coli 100,000 x g particulate fraction and 1% in the fraction from yeast. To demonstrate the utility of the E. coli expression system for studying structure/function relationships of the flavin-containing monooxygenase, two mutant FMOs were expressed and characterized. One mutant, formed by deletion of a putative membrane-anchoring peptide (the 26 carboxyl terminal amino acids) was tested for membrane association. No difference in the subcellular distribution was found between the truncated and unmodified proteins, suggesting that the 26-residue COOH-terminal peptide is not important in membrane association. Catalytic analysis of the truncated FMO 1B1 established its functional similarity to the full-length protein, indicating that the COOH terminus does not contribute to any of the unique properties of the lung enzyme.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8449937 TI - Human coagulation factor X deficiency caused by a mutant signal peptide that blocks cleavage by signal peptidase but not targeting and translocation to the endoplasmic reticulum. AB - Human factor XSanto Domingo is a form of coagulation factor X in which a mutation within the signal peptide region of the precursor protein has been correlated genetically with a severe deficiency of factor X in the affected individual. A point mutation results in substitution of Arg for Gly at the critical -3 position of the factor X signal peptide. To determine the biochemical effect of this mutation on the biosynthesis of factor X, the wild-type and mutant factor X cDNAs were subcloned into a vector for transcription and translation in vitro. Translation products of mRNAs encoding portions of both mutant and wild-type proteins were used in a systematic biochemical approach to evaluate directly the effect of the mutation on targeting, transport, and proteolytic processing in vitro. The results show that targeting and transport of factor XSanto Domingo to the endoplasmic reticulum are functionally dissociated from the removal of the signal peptide by signal peptidase. Factor XSanto Domingo is translocated into the endoplasmic reticulum but not processed by signal peptidase. Transient expression of the wild-type and mutant factor X in human embryonic kidney 293 cells revealed apparently normal secretion of the glycosylated two-chain form of factor X but no secretion of factor XSanto Domingo. Thus, the inability of signal peptidase to cleave factor XSanto Domingo is directly responsible for the absence of circulating factor X and leads to the bleeding diathesis in the affected individual. PMID- 8449938 TI - Cell surface site for mitogenic interaction of erythropoietin receptors with the membrane glycoprotein encoded by Friend erythroleukemia virus. AB - The membrane glycoprotein (gp55) encoded by the env gene of Friend spleen focus forming virus (SFFV) causes mitogenesis of infected erythroblasts and is inefficiently (3-5%) processed from the rough endoplasmic reticulum (RER) to plasma membranes. Recent evidence suggested that gp55 binds to erythropoietin receptors (EpoR) in the RER, and it was proposed that this intracellular interaction causes mitogenesis (Li, J.-P., D'Andrea, A. D., Lodish, H. F., and Baltimore, D. (1990) Nature 343, 762-764). Other evidence has indicated that the plasma membrane component (gp55P) can also complex with EpoR. To identify the site of functional complexes and to study the factors that control their formation, we analyzed eight SFFV env mutants that contain in-frame deletions or linker insertions. The three nonpathogenic mutants encode gp55s that fail to leave the RER, whereas the five pathogenic mutants encode glycoproteins that occur on cell surfaces. Although BaF3 hematopoietic cells are interleukin 3 (IL 3)-dependent, a cellular derivative BaF3/EpoR that contains EpoR survives and grows in either IL-3 or erythropoietin (Epo). The five pathogenic SFFV env mutants converted BaF3/EpoR but not BaF3 cells to growth factor independence, whereas the nonpathogenic mutants did not eliminate growth factor requirements of any cells. Studies using 125I-Epo and the covalent cross-linking reagent disuccinimidyl suberate provided unambiguous evidence for ternary complexes of 125I-Epo.EpoR.gp55P on surfaces of all factor-independent cells. Size of the cell surface complex was correspondingly reduced in the case of a newly isolated SFFV mutant that encodes a severely truncated (M(r) approximately 41,000) but mitogenically active env glycoprotein. Our results support the hypothesis that activation of EpoR by the SFFV env glycoprotein occurs exclusively on cell surfaces. PMID- 8449939 TI - Insulin-induced phosphorylation of the 46- and 52-kDa Shc proteins. AB - The products of the shc gene appear to be substrates for activated oncogenic tyrosine kinases, such as v-Src and v-Fps and activated tyrosine kinase receptors like the epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) receptors. We investigated whether the Shc proteins are targets for the activated insulin receptor tyrosine kinase. Here we show that the 46- and 52-kDa Shc proteins are rapidly phosphorylated upon insulin receptor activation in fibroblasts expressing elevated levels of human insulin receptors. Furthermore, we observed insulin-induced association of a 23-kDa protein with the Shc proteins. These effects on Shc proteins are similar to those observed after EGF and PDGF treatment. In contrast to the observed Shc-EGF receptor association, we did not detect association between the Shc proteins and the insulin receptor. We conclude that the Shc proteins are common elements in a signal transduction pathway that is shared by EGF, PDGF, and insulin. PMID- 8449940 TI - Isolation and immunochemical characterization of eukaryotic translation initiation factor 5 from Saccharomyces cerevisiae. AB - Eukaryotic translation initiation factor 5 (eIF-5), which catalyzes the hydrolysis of GTP bound to the 40 S ribosomal initiation complex has been purified from yeast cell lysates. The purified factor eluted from gel filtration columns as a protein of apparent M(r) = 45,000-50,000. However, when the purified preparation was analyzed by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, two distinct polypeptides of apparent M(r) = 54,000 and 56,000 were observed. Each of the two polypeptides individually was found to contain eIF-5 activity, and they were immunologically related to each other. In less pure preparations of yeast eIF-5, however, a significant proportion of eIF-5 activity eluted from gel filtration columns as a protein of M(r) > 140,000. Immunochemical methods were therefore employed to determine the molecular structure of eIF-5 in crude yeast cell lysates. Antisera against purified yeast eIF-5 were prepared in rabbits and shown to be highly potent in inhibiting eIF-5 mediated 80 S initiation complex formation. When crude eIF-5 preparations, as well as yeast cells that were lysed directly into a denaturing buffer containing 3% sodium dodecyl sulfate, were analyzed by Western blots probed with affinity purified anti-eIF-5 antibodies, a major immunoreactive polypeptide (apparent M(r) = 54,000) and a minor band (apparent M(r) = 56,000) were observed. No precursor forms of molecular weight higher than 56,000 were detected in any preparations. These results suggest that yeast eIF-5 is a monomeric protein of apparent M(r) = 50,000-56,000. PMID- 8449941 TI - Characterization of two isoforms of protein kinase C in the nervous system of Aplysia californica. AB - By molecular cloning Kruger et al. (Kruger, K. E., Sossin, W. S., Sacktor, T. C., Bergold, P. J., Beushausen, S., and Schwartz, J. H. (1991) J. Neurosci. 11, 2303 2313) provided evidence for three isoforms of protein kinase C (PKC) in Aplysia, two of which, Apl I and Apl II, are expressed abundantly in the nervous system. We resolve two major kinase activities from nervous tissue by column chromatography on DEAE-cellulose and hydroxylapatite (HAP), one Ca(2+)-activated and the other Ca(2+)-independent. We show that these two activities correspond to the previously cloned Apl I and II. These two isoforms appear to be the only major PKCs present in nervous tissue. The Apl I kinase is strongly activated by cis-fatty acids but only in the presence of Ca2+. Thus functionally, Apl I is more like the alpha and beta isoforms of vertebrate PKC, than to the vertebrate neural gamma isoform. The Apl II kinase is Ca(2+)-independent and resembles vertebrate PKC epsilon. The simplicity of the PKC isoform distribution in Aplysia makes this mollusc an attractive animal for understanding the differential regulation and physiological activities of Ca(2+)-activated and Ca(2+) independent PKCs. PMID- 8449942 TI - Characterization of the ets oncogene family member, fli-1. AB - The recently cloned fli-1 gene is a member of the ets oncogene family that is preferentially expressed in hematopoietic cells. It is a target of dysregulation by Friend leukemia virus insertion and translocation in Ewing's sarcoma and neuroepithelioma. In this report, we have studied the function and regulation of both murine and human fli-1. Analysis of the human and mouse fli-1 proteins showed that fli-1 binds to specific DNA sequences highly related to m-ets-2 binding sites. Methylation protection experiments showed that fli-1 and m-ets-2 contacted the same nucleotides in two different binding sites. The fli-1 protein was shown to be a transcriptional activator in co-transfection studies. Stimulation of murine bone marrow macrophages by mediators of inflammation, such as lipopolysaccharide, phorbol 12-myristate 13-acetate, interleukin-1, and interferon-gamma resulted in the reduced expression of fli-1 mRNA. fli-1 was only expressed in a defined subset of human erythroleukemia cell lines. PMID- 8449943 TI - 8-Cl-cAMP induces truncation and down-regulation of the RI alpha subunit and up regulation of the RII beta subunit of cAMP-dependent protein kinase leading to type II holoenzyme-dependent growth inhibition and differentiation of HL-60 leukemia cells. AB - 8-Cl-cAMP, a site-selective cAMP analog, induces growth inhibition in a variety of cell types of human cancer cell lines. This inhibitory effect of 8-Cl-cAMP was related to its ability to differentially regulate type I versus type II cAMP dependent protein kinase. In the present study we demonstrated a unique mechanism of action of 8-Cl-cAMP in the regulation of these kinase isozymes in HL-60 human promyelocytic leukemia cells. High-performance liquid chromatography (HPLC) resolved various isoforms of protein kinase present in HL-60 cells. In control cells, type I protein kinase (PKI) comprised more than 90% and type II protein kinase (PKII) less than 10% of the total cAMP-stimulated kinase activity. Treatment with 8-Cl-cAMP (5 microM, 72 h) decreased PKI to a level below 30% of that in untreated control cells and markedly increased PKII composed of three peaks. Photoaffinity labeling/SDS-polyacrylamide gel electrophoresis of column fractions identified the molecular species of regulatory (R) subunits present in protein kinases. Control cells contained high levels of the 48-kDa protein (RI) that composed PKI and low levels of the 50-kDa RII associated with PKII. 8-Cl cAMP treatment brought about a decrease in the 48-kDa RI along with an increased formation of the truncated 34-kDa RI associated with PKI and an increase in the 50-54-kDa species of RII associated with PKII. A similar protein kinase profile as that shown by 8-Cl-cAMP treatment was observed in cells infected with the human RII beta retroviral vector: the 48-kDa RI of PKI decreased and the 52- and 54-kDa RII associated with PKII increased as compared with uninfected control cells. However, unlike 8-Cl-cAMP treatment, RII beta retroviral vector infection brought about no increase in the 34-kDa-truncated RI but exhibited an increase in the free 48-kDa RI subunit. As the 48-kDa RI and the 50-kDa RII were present in control cells, the enhanced expression of the 52- and 54-kDa RII proteins was due to overexpression of the RII beta gene. We identified the 48-kDa RI as RI alpha, the 50-kDa RII as RII alpha, the 52-kDa RII as RII beta, and the 54-kDa RII as the phosphorylated form of either the RII alpha or RII beta subunit. In vivo labeling experiments using [3H]8-Cl-cAMP demonstrated that 8-Cl-cAMP enters cells and binds to both PKI and PKII.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8449944 TI - Sugar chains of serum transferrin from patients with carbohydrate deficient glycoprotein syndrome. Evidence of asparagine-N-linked oligosaccharide transfer deficiency. AB - The structure of over 93% of the sugar chains of serum transferrin purified from three patients with carbohydrate-deficient glycoprotein (CDG) syndrome was Neu5Ac alpha 2-->6Gal beta 1-->4GlcNAc beta 1-->2Man alpha 1-->6 (Neu5Ac alpha 2-->6Gal beta 1-->4GlcNAc beta 1-->2Man alpha 1-->3)Man beta 1-->4GlcNac beta 1-->4GlcNAc, similar to that in a healthy control. On chromatofocusing, CDG syndrome transferrin was separated into three major isoforms, S4, S2, and S0, containing 4, 2, and 0 sialic acids/molecule at pH 5.12 (5.16), 5.42, and 5.80, respectively. On 7.5% SDS-polyacrylamide gel electrophoresis, the molecular masses of transferrin isoforms S4, S2, and S0 were 80, 77, and 74 kDa, respectively. Transferrin isoforms S4 and S2 were linked to 2 and 1 mol of sialylated biantennary sugar chain/transferrin molecule, on the other hand, isoform S0 was not linked to any asparagine-N-linked oligosaccharide. Accordingly, CDG syndrome can be concluded to be an asparagine-N-linked oligosaccharide transfer deficiency, although the primary deficient enzyme has not yet been determined. PMID- 8449945 TI - Tissue-specific expression and alternative mRNA processing of the mammalian acetylcholinesterase gene. AB - This study examines the tissue specificity and the gene products arising from alternative mRNA processing of the mammalian acetylcholinesterase gene. By splicing either alternative exons 5 or 6 in the mouse and human genes directly to the invariant exons (exons 2, 3, and 4), we show that the acetylcholinesterase species expressed by transfected recombinant DNA have the properties expected for the respective enzyme forms found in tissue. Antisense mRNA derived from these cDNAs has been employed to examine differential splicing in various tissues. In most cells, the hydrophilic form of AChE encoded by the exon 4 to exon 6 splice to form the mRNA is the predominant species. However, splicing of exon 4 to exon 5, yielding a mRNA encoding the glycophospholipid-linked form of acetylcholinesterase, is seen primarily in erythroid and to a lesser extent in AtT-20 cells. Only small amounts of this mRNA species appear in some other cells in culture. A novel third mRNA species, which arises from an extension of exon 4 without splicing to a downstream exon, is seen in mouse erythroid but not in human erythroid cells. A cDNA encoding this species when expressed in COS cells gives rise to a unique hydrophilic, secreted form of acetylcholinesterase. Transfection of a human genomic clone into mouse erythroleukemia cells does not result in the appearance of a mRNA species with an extension of exon 4 as seen with the endogenous mouse gene. Hence, differential splicing between the mouse and human genes appears intrinsic to the coding sequence and is not dependent solely on specific factors in the mouse erythroleukemia cell. PMID- 8449946 TI - Determination of the distance between the oligosaccharyltransferase active site and the endoplasmic reticulum membrane. AB - By in vitro transcription/translation of model proteins in the presence of dog pancreas microsomes, we have measured the minimum distance of an acceptor site from the lumenal end of a transmembrane segment required for N-linked glycosylation, both when the acceptor site is placed N- and C-terminally to the membrane anchor. We observe a sharp threshold at a distance of 12-14 residues, suggesting that the oligosaccharyltransferase active site is 30-40 A above the membrane and is oriented roughly parallel to the membrane surface. PMID- 8449947 TI - Inhibitors of mitochondrial carnitine palmitoyltransferase I limit the action of proteases on the enzyme. Isolation and partial amino acid analysis of a truncated form of the rat liver isozyme. AB - Our objective was to isolate from rat liver mitochondria the malonyl-CoA regulated and detergent-labile enzyme, carnitine palmitoyltransferase I (CPT I), whose properties and relationship to CPT II have been the subject of debate. After exposure of mitochondria to the dinitrophenol derivative of etomoxir-CoA (DNP-Et-CoA, a covalent inhibitor of CPT I), followed by detergent solubilization and blue Sepharose chromatography, the DNP-Et-labeled CPT I could be readily visualized on immunoblots using an anti-DNP monoclonal antibody. This material was used to raise a rabbit polyclonal antibody that recognized CPT I regardless of whether it was carrying a covalent ligand. Exposure of membranes from untreated mitochondria to a mixture of trypsin and chymotrypsin caused rapid loss of CPT I activity with a concomitant disappearance of immunodetectable protein. However, inclusion of malonyl-CoA in such incubations afforded major protection of CPT I activity. Under these conditions CPT I simply underwent truncation from approximately 90 to approximately 82 kDa. This was also true if CPT I had first been labeled with Et-CoA or DNP-Et-CoA prior to protease treatment. Thus, the presence of an inhibitor, whether reversible or irreversible, at the active site of CPT I limited the action of trypsin/chymotrypsin to removal of a small portion of the protein which was probably not necessary for catalytic function. These and other experiments with antibodies and proteases provided additional insight into the membrane topology of CPT I. They also strengthened our conviction that CPT I and CPT II are distinct proteins and that the former exists as tissue-specific isoforms. Finally, the 82-kDa truncated form of rat liver CPT I was isolated and subjected to partial amino acid analysis. Four unambiguous peptide sequences were obtained. PMID- 8449948 TI - Cloning, sequencing, and expression of a cDNA encoding rat liver carnitine palmitoyltransferase I. Direct evidence that a single polypeptide is involved in inhibitor interaction and catalytic function. AB - We report the isolation and characterization of a full-length cDNA encoding rat liver carnitine palmitoyltransferase I (CPT I). Oligonucleotides corresponding to two tryptic peptides derived from the malonyl-CoA/etomoxir-CoA-binding protein of rat liver mitochondria (Esser, V., Kuwajima, M., Britton, C. H., Krishnan, K., Foster, D. W., and McGarry, J. D. (1993) J. Biol. Chem. 268, 5810-5816) were used to screen a rat liver cDNA library constructed in the plasmid cloning vector, pcDV. The clone obtained consisted of a 102-nucleotide 5'-untranslated region, a single open reading frame of 2,319 bases predicting a protein of 773 amino acids (M(r) = 88,150), and a 3'-untranslated segment of 1,957 nucleotides followed by the poly(A)+ tail. A 0.9-kilobase fragment of the cDNA recognized a single species of mRNA (approximately 4.7 kilobases in size) in rat liver. The identity of the cDNA was confirmed by the findings that (i) the open reading frame encoded all four peptides found in the original protein; (ii) transfection of COS cells with the cDNA subcloned into the expression vector, pCMV6, resulted in a selective and 10-20-fold induction of a malonyl-CoA- and etomoxir-CoA-sensitive CPT activity; and (iii) the overexpressed product was readily detected on Western blots by an antibody raised against the starting material. It seems likely that the de novo synthesized enzyme is targeted to the mitochondrial outer membrane via a leader peptide and that the mature protein achieves membrane anchoring through a stretch of 20 amino acids present near its amino terminus. The predicted amino acid sequence of the protein shows regions of strong identity with those of three other rat acyltransferases, namely, liver CPT II, liver carnitine octanoyltransferase, and brain choline acetyltransferase. The findings provide the first insight into the structure of a CPT I isoform. They also establish unequivocally that CPT I and CPT II are distinct proteins and that inhibitors of CPT I interact within its catalytic domain, not with an associated regulatory component. PMID- 8449949 TI - Cross-linking of the cms-T maize mitochondrial pore-forming protein URF13 by N,N' dicyclohexylcarbodiimide and its effect on URF13 sensitivity to fungal toxins. AB - URF13 is a membrane protein unique to mitochondria from maize having the Texas male-sterile cytoplasm (cms-T), which is capable of permeabilizing biological membranes in the presence of a family of pathotoxins (T-toxins) produced by certain fungi or the insecticide methomyl. The carboxylate-specific reagent dicyclohexylcarbodiimide has been shown previously to protect URF13-containing membranes against the permeabilizing effects of added T-toxin or methomyl. Dicyclohexylcarbodiimide was found to covalently cross-link URF13 into higher order oligomers, including dimers, trimers, and tetramers, in isolated cms-T mitochondria and Escherichia coli cells expressing URF13. In intact E. coli cells and isolated spheroplasts, the observed protection against the effects of methomyl was not associated with the appearance of dimers but was correlated with the appearance of cross-linked trimers and tetramers. Following treatment of E. coli cells expressing URF13 with dicyclohexylcarbodiimide, the specific binding of tritiated T-toxin was reduced by 50% and all binding cooperativity was lost. A similar decrease in the level of T-toxin binding and loss of binding cooperativity were observed with site-directed, T-toxin-insensitive URF13 mutants at aspartate 39, the residue known to undergo reaction with dicyclohexylcarbodiimide. When coupled with a postulated three membrane-spanning helical model of URF13, these results provide initial insights into the intermolecular interactions involved in URF13 oligomer formation. PMID- 8449950 TI - Assembly and structural properties of subsaturated chromatin arrays. AB - Nucleosomes have been reconstituted onto dodecameric repeats of a 208-base pair nucleosome positioning sequence at various subsaturating molar ratios of histone octamer to DNA repeat (r). These reconstitutes have been characterized with respect to lattice site occupancy distributions, nucleosome positioning, chromatin folding, and histone octamer dissociation. Reconstitution at 0.3 < or = r < or = 0.9 produces subsaturated chromatin templates with distinct compositional limits, n +/- 2 nucleosomes, where n is the average number of nucleosomes present on the template at that r value. Nucleosomes on subsaturated arrays occupy the same set of specific positions within the repeat unit as they do on saturated templates, with only very slight differences in the relative frequency of occupation of the various positions. The nucleosomes on very subsaturated templates, i.e. r < or = 0.5, are generally spread out. However, some nucleosome clustering is observed on these very subsaturated templates. These results indicate that assembly of nucleosomes onto this DNA lattice is not a strongly cooperative process. In 200 mM NaCl, subsaturated reconstitutes exhibit reduced levels of folding and histone octamer dissociation compared with saturated arrays. These results provide a framework for understanding the structural features of regions of chromatin partially depleted of nucleosomes. PMID- 8449951 TI - Effects of DNA lesions on transcription elongation by T7 RNA polymerase. AB - T7 phage RNA polymerase was used to transcribe a series of DNA templates bearing any of several precisely localized lesions. Lesions were positioned downstream of the T7 promoter on either strand of the DNA template to investigate the effects of these lesions on elongation of transcription. The following four types of DNA modifications were studied: 1) 3-hydroxy-2-hydroxymethyltetrahydrofuran (tetrahydrofuran), a synthetic apurinic/apyrimidinic site; 2) 8-oxoguanine (8 oxodG), an oxidized derivative of guanine; 3) N-acetyl-2-aminofluorene (AAF) modified guanine; 4) 2-aminofluorene (AF) modified guanine. None of these lesions blocked transcription elongation when they were located on the non-template strand. Lesions on the template strand blocked elongation with varied efficiency. The series of AAF-dG, AF-dG, and tetrahydrofuran lesions showed a progressively decreasing ability to block elongation, while 8-oxo-dG caused little, if any, premature termination. T7 RNA polymerase was able to read through all of the lesions with sufficient efficiency to permit chain termination sequencing using the read-through products as templates. AAF-dG and AF-dG adducts did not induce detectable misreading. Adenine and, more rarely, cytosine were incorporated opposite 8-oxo-dG, as observed for translesional synthesis by DNA polymerases. Adenine was most commonly inserted opposite the non-instructional abasic site analogue, although a minor fraction of guanine was incorporated. PMID- 8449952 TI - Identification of a major binding site for complement C3 on the IgG1 heavy chain. AB - Activation of the alternative pathway of complement by immune complexes involves the covalent attachment of the third component (C3) to the IgG heavy chain. In order to localize the site/sites of attachment, adducts of human C3.IgG were digested in situ with endoproteinase Lys-C and Staphylococcus aureus V8 protease, and the fragments were analyzed. The dimeric peptide containing the covalent bond, identified by alkylation of the free thiol group (Cys1010) with iodo[14C]acetamide, was isolated by high-performance liquid chromatography fractionation. A double sequence with NH2 termini corresponding to position 134 of IgG heavy chain and position 1002 of the C3 alpha' chain was found by analysis with automated Edman degradation. The intact dimeric peptide had a mass of 3453 Da and was composed of IgG and C3 fragments with predicted sizes of 23 and 12 residues, respectively. The IgG peptide includes a cluster of six potential acceptor sites for ester bond formation. Thus, it appears that C3 binding is limited to a single region within the CH1 domain of the IgG1 heavy chain. PMID- 8449953 TI - A novel short isoform of the D3 dopamine receptor generated by alternative splicing in the third cytoplasmic loop. AB - The mouse D3 dopamine receptor has been cloned from olfactory tubercle cDNA using polymerase chain reaction and has been found to exist in two alternatively spliced forms. These two mRNA isoforms differ by the presence or absence of 63 base pairs (bp), which encode 21 amino acids in the putative third cytoplasmic loop of the receptor. The longer form corresponds to the previously reported rat D3 dopamine receptor, to which it bears sequence homology of 94%. Northern blot analysis shows the mouse D3 receptor to be most abundant in the olfactory tubercle. Expression studies show the novel short D3 isoform to bind dopaminergic ligands with a D3-like pharmacological profile. Polymerase chain reaction analysis on different mouse brain regions shows the long and short D3 receptors to be present in the same tissues, the longer form invariably being the predominant one. Analysis of the gene for the mouse D3 dopamine receptor shows that no separate exon encodes the 63-bp stretch and reveals the presence of a consensus sequence for an acceptor site at the 3' end of the 63-bp stretch. This suggests that an internal acceptor site in the exon coding for the distal part of the third cytoplasmic loop directs alternative splicing of the D3 dopamine receptor. PMID- 8449954 TI - Cellular detoxification of tripeptidyl aldehydes by an aldo-keto reductase. AB - Calpain inhibitor I, N-acetyl-leucyl-leucyl-norleucinal (ALLN), a cell-permeable synthetic tripeptide with an aldehyde at its C terminus specifically inhibits the activity of cysteine proteases. Since the regulated degradation of 3-hydroxy-3 methylglutaryl-CoA reductase in Chinese hamster ovary (CHO) cells is blocked by ALLN and ALLN has a cytotoxic effect on cells, we attempted to isolate ALLN resistant cells that overproduce an ALLN-sensitive protease(s). However, we obtained an ALLN-resistant cell line that overproduced P-glycoprotein (Sharma, R. C., Inoue, S., Roitelman, J., Schimke, R. T., and Simoni, R. D. (1992) J. Biol. Chem. 267, 5731-5734). To circumvent the multidrug resistance (MDR) phenotype during selection, we have stepwise selected an ALLN-resistant cell line of CHO cells in the presence of verapamil, a competitive inhibitor of P-glycoprotein. These non-MDR ALLN-resistant cells overexpress a 35-kDa protein and have increased aldo-keto reductase activity. Partial amino acid sequences of the 35 kDa protein are highly homologous to members of the aldo-keto reductase superfamily. The aldo-keto reductases are NADPH-dependent oxidoreductases and catalyze reduction of a wide range of carbonyl compounds such as aldehydes, sugars, and ketones. Our findings support the concept that a physiological function for aldo-keto reductases may be detoxification. PMID- 8449955 TI - Characterization of PEA-15, a major substrate for protein kinase C in astrocytes. AB - Astrocytes in the central nervous system are involved in a variety of functions including storage of glycogen, maintenance of the extracellular ionic equilibrium, and support for the migration and the differentiation of neurons. Astrocytes express membrane receptors allowing them to respond to extracellular signals. Activation of receptors induces a cascade of events, such as stimulation of protein kinases and subsequent phosphorylation of target proteins. To understand the regulatory processes underlying neuroglial interactions, attempts were made to identify major phosphorylated proteins in striatal astrocytes, grown in primary culture and labeled with [32P]phosphate. Two-dimensional gel electrophoresis revealed a major doublet, Pa and Pb, of highly labeled spots, with a low molecular weight (M(r) = 15,000) and acidic pI (pI = 5.2 and 5.3, respectively). Using an enriched, heat-stable, cytosolic fraction, Pa and Pb were eluted from semi-preparative two-dimensional gels and subjected to a limited proteolysis and partial microsequencing. The same sequences were obtained within Pa and Pb and had no homology with other known protein. Antibodies raised against corresponding synthetic peptides confirm that the doublet represents two isoelectric variants of the same protein, which also exists under a nonphosphorylated form, N. We propose to name this protein PEA-15, for Phosphoprotein Enriched in Astrocytes-15 kDa, according to its large enrichment in these cells. Treatment of intact astrocytes with 12-O-tetradecanoylphorbol-13 acetate (TPA), which stimulates protein kinase C (PKC), increased the phosphorylation of the more acidic spot (Pb) while decreasing Pa intensity. Stimulations of astrocytes known to increase PKC activity, i.e. noradrenaline, or its inhibition by decreasing extracellular calcium concentrations, staurosporine, or desensitization following long term treatment with TPA, induced a phosphorylation or a dephosphorylation of PEA-15, respectively. Using purified PKC, PEA-15 appeared to be a good substrate in vitro. Two-dimensional peptide mapping revealed that the phosphorylation site in intact cells was identical with the site phosphorylated by PKC in vitro. Mapping the phosphopeptides by HPLC following endolysine C treatment lead to the identification of a sequence, phosphorylated in intact astrocytes and in vitro by PKC, containing a consensus site for PKC: LTRIPSAKK. Antibodies raised against a synthetic peptide derived from this sequence recognized N and Pa in control conditions and Pb after its dephosphorylation. Thus, PEA-15 is an endogenous substrate for PKC, the kinase mediating the transition from Pa to Pb. PMID- 8449956 TI - Soluble lactose-binding lectin from rat intestine with two different carbohydrate binding domains in the same peptide chain. AB - Of the multiple soluble lactose-binding (S-Lac) lectins in rat intestine, the major one, tentatively designated RI-H, was previously isolated as a polypeptide of molecular weight approximately 17,000. We here report the sequence of RI-H, as determined both at the peptide level and at the nucleotide level. Surprisingly the cDNA encodes a protein of molecular weight approximately 36,000, and this protein contains two homologous but distinct domains each with sequence elements that are conserved among all S-Lac lectins. The C-terminal domain, designated domain II, corresponds to the lectin with M(r) of 17,000 previously isolated from intestinal extracts and shown to have lactose binding activity. By preparing recombinant protein containing only the N-terminal domain, designated domain I, we here directly demonstrate that it too binds lactose and a related range of sugars that are roughly similar to domain II, but clearly distinct. The new lectin, which we designate L-36, is highly expressed in full-length form in rat small and large intestine and stomach but was not detected in eight other tissues including lung, liver, kidney, and spleen. Each domain has approximately 35% sequence identity with the other domain and with the carbohydrate-binding domain of L-29, another S-Lac lectin, but only about 15% identity with other known S-Lac lectins. PMID- 8449957 TI - A second member of the novel Ca(2+)-dependent protein kinase family from Paramecium tetraurelia. Purification and characterization. AB - The ciliated protozoan Paramecium tetraurelia contains two protein kinase activities (CaPK-1 and CaPK-2) that are dependent on Ca2+ (Gundersen, R. E., and Nelson, D. L. (1987) J. Biol. Chem. 262, 4602-4609). We purified Ca(2+)-dependent protein kinase-1 (CaPK-1) 1,000-fold from the EGTA-extracted soluble fractions of Paramecium. The purified enzyme was a single polypeptide of 52 kDa on SDS polyacrylamide gel electrophoresis with a native molecular mass of 60,000, suggesting that the active enzyme is a monomer. The purified kinase used casein as the best substrate in vitro, and its activity was absolutely dependent on Ca2+. The physical, catalytic and regulatory properties were clearly distinct from those of casein kinase, protein kinase C, and Ca2+/calmodulin-dependent protein kinases. CaPK-1 was half maximally activated by submicromolar (0.2 microM) free Ca2+, and the purified kinase bound Ca2+ in a blot overlay assay. CaPK-1 and the previously characterized CaPK-2 were biochemically and immunologically different enzymes sharing a similar activation mechanism. CaPK-1 and CaPK-2 appear to be members of a new family of Ca(2+)-dependent protein kinases. A protein immunologically related to the CaPKs was also detected in rat brain. PMID- 8449958 TI - Translational control of 5-aminolevulinate synthase mRNA by iron-responsive elements in erythroid cells. AB - Hemoglobin synthesis in red cells is the major iron utilization pathway in the human body and accounts for > 80% of systemic iron turnover. The first step in erythroid heme biosynthesis is catalyzed by a tissue-specific isoform of 5 aminolevulinate synthase (ALAS). The previous identification of iron-responsive elements in the 5'-untranslated region of human and murine erythroid ALAS mRNA raised the intriguing possibility that eALAS expression might be under iron dependent translational control. As a consequence, a single post-transcriptional regulatory system could coordinate cellular iron acquisition via the transferrin receptor, storage via ferritin, and utilization via eALAS. We directly demonstrate iron-dependent translational regulation of eALAS mRNA in murine erythroleukemia (MEL) cells. The iron-responsive element motif contained in eALAS mRNA is shown to be sufficient to confer translational control to a reporter mRNA both in transfected MEL cells and in vitro. PMID- 8449960 TI - Expression of human aspartyl-tRNA synthetase in Escherichia coli. Functional analysis of the N-terminal putative amphiphilic helix. AB - Mammalian aspartyl-tRNA synthetase occurs in the multienzyme complex of aminoacyl tRNA synthetases, while bacterial and yeast aspartyl-tRNA synthetases exist as free soluble enzymes. Cloning and sequencing of mammalian aspartyl-tRNA synthetase revealed a newly evolved N-terminal 32-amino-acid sequence, which contains a putative amphiphilic helix (Jacobo-Molina, A., Peterson, R., and Yang, D. C. H. (1989) J. Biol. Chem. 264, 16608-16612). Human aspartyl-tRNA synthetase (hDRS) and an N-terminal 32-residue truncated form of human aspartyl-tRNA synthetase (hDRS delta 32) were expressed in Escherichia coli under the control of the inducible tac promoter as glutathione-S-transferase (GST) fusion proteins linked through a thrombin cleavage site. The GST-hDRS fusion protein and the GST hDRS delta 32 were purified by affinity chromatography on glutathione-agarose and were fully active in aspartylation of mammalian tRNA. After cleavage of GST from the fusion proteins by thrombin, hDRS and hDRS delta 32 were purified by affinity chromatography on tRNA-Sepharose. Both hDRS and hDRS delta 32 were present as a mixture of monomeric and dimeric forms. GST-hDRS formed high molecular weight aggregates while GST-hDRS delta 32 was a dimeric protein. Both hDRS and hDRS delta 32 bound to hydrophobic interaction gels such as aminohexyl-agarose. In the absence of propylene glycol, hDRS bound to amino-hexyl-agarose weaker than hDRS delta 32, but, in the presence of 50% propylene glycol, hDRS bound tighter than hDRS delta 32. Both hDRS and hDRS delta 32 were fully active in aspartylation of mammalian tRNA and ATP-PPi exchange. In comparison to the N-terminal truncated form, the full-length enzyme showed greater thermal stability and ATP-PPi exchange activity but lower aminoacylation activity. The catalytic constant of hDRS delta 32 for aminoacylation of tRNA was 2-fold higher than that of hDRS. The Michaelis-Menten constants for aspartic acid and tRNAAsp were 302 microM and 13 nM for hDRS, and 29 microM and 130 nM for hDRS delta 32, respectively. These results suggest that the newly evolved N-terminal peptide in hDRS may modulate the enzymatic activity, the stability, and the chromatographic behavior of hDRS. The structure and function of the N-terminal peptide in aspartyl-tRNA synthetase and in the synthetase complex will be discussed. PMID- 8449959 TI - Identification and quantification of Gi-type GTP-binding proteins that copurify with a pituitary somatostatin receptor. AB - Somatostatin (SRIF) receptors of GH4C1 cells occupied with biotinyl-NH-[Leu8,D Trp22,Tyr25] somatostatin28 (bio-S28) have been affinity purified over streptavidin affinity columns (Eppler, C. M., Zysk, J. R., Corbett, M., and Shieh, H.-M. (1992) J. Biol. Chem. 267, 15603-15612). This procedure results in the copurification of a single subtype of SRIF receptor (SSTR2) and associated guanine nucleotide-binding proteins (G proteins) that are coupled to these receptors. For accurate quantification it was necessary to: (i) use homogenous recombinant standards; (ii) accurately assess the purity of standards; (iii) determine recovery of G proteins during sample preparation and Western blotting; and (iv) account for cross-reactivity among antisera. Four pertussis toxin sensitive G proteins were quantified with previously characterized polyclonal antisera. Gi alpha 1 also was measured with a novel, more sensitive monoclonal antibody (7H7). Go alpha and Gi alpha 2 but not Gi alpha 1 and Gi alpha 3 were detected in membrane extracts prepared from GH4C1 cells. In contrast, the G proteins copurified with SSTR2 receptors were predominantly Gi alpha 2 (50% of total G protein) and Gi alpha 3 (36% of total G protein), whereas Go alpha and Gi alpha 1 were negligible. G beta subunits also were detected. Silver staining confirmed the absence of a 39-kDa protein, corresponding to the M(r) of Go alpha associated with purified SRIF receptor-G protein complexes. These data suggest that SRIF receptors selectively couple to two G proteins, one of which is sparsely expressed in GH4C1 cells; the data conform to the notion that SRIF receptors discriminate between similar pertussis toxin-sensitive G proteins. PMID- 8449961 TI - Multiple genes encode the major surface glycoprotein of Pneumocystis carinii. AB - The major surface antigen of Pneumocystis carinii, a life-threatening opportunistic pathogen in human immunodeficiency virus-infected patients, is an abundant glycoprotein that functions in host-organism interactions. A monoclonal antibody to this antigen is protective in animals, and thus this antigen is a good candidate for development as a vaccine to prevent or control P. carinii infection. We have cloned and sequenced seven related but unique genes encoding the major surface glycoprotein of rat P. carinii. Partial amino acid sequencing confirmed the identity of these genes. Based on Southern blot studies using chromosomal or restricted DNA, the major surface glycoproteins are the products of a multicopy family of genes. The predicted protein has an M(r) of approximately 123,000, is relatively rich in cysteine residues (5.5%) that are very strongly conserved, and contains a well conserved hydrophobic region at the carboxyl terminus. The presence of multiple related msg genes encoding the major surface glycoprotein of P. carinii suggests that antigenic variation is a possible mechanism for evading host defenses. Further characterization of this family of genes should allow the development of novel approaches to the control of this pathogen. PMID- 8449962 TI - Topology of the ExbB protein in the cytoplasmic membrane of Escherichia coli. AB - The ExbB protein together with the ExbD and TonB proteins is involved in energy coupled transport across the outer membrane of Escherichia coli. To understand this unusual process it is required to determine the subcellular location of ExbB and its transmembrane arrangement. Using ExbB-beta-lactamase fusion proteins as reporters for a periplasmic versus a cytoplasmic location of the fusion sites, and accessibility of ExbB in spheroplasts and cell lysates to aminopeptidase K, trypsin, and proteinase K, we arrived at a model of ExbB topology in the cytoplasmic membrane. Starting with the N terminus in the periplasm ExbB contains three transmembrane segments (residues 16-39, 128-155, 162-194) a small periplasmic loop and two large portions in the cytoplasm. Two of the 18 fusion proteins studied, ExbB34-beta-lactamase and ExbB41-beta-lactamase, conferred a high ampicillin resistance. Protease experiments revealed a high respectively low percentage of the molecules in a reverse transmembrane orientation. Both proteins were lacking positive charges at the inner side of the cytoplasmic membrane which determine the orientation of transmembrane segments. PMID- 8449963 TI - Antibacterial 15-kDa protein isoforms (p15s) are members of a novel family of leukocyte proteins. AB - We have previously described the isolation and initial characterization of functionally distinct 15-kDa protein isoforms (p15s) from rabbit polymorphonuclear leukocytes (PMN) that bind with high affinity to Escherichia coli and modulate the antibacterial actions of other leukocyte proteins on this Gram-negative bacterium. We now report the cloning and sequencing of two distinct cDNAs from a rabbit bone marrow library that encode p15s differing at only 2 residues (His-3, Arg-88 versus Arg-3, Trp-88). Tryptophan-directed chemical cleavage of two isoforms purified from a single rabbit confirms the existence of multiple isoforms with distinct function and primary structure in a single rabbit. The p15 cDNAs encode putative signal sequences and studies of cellular and subcellular localization indicate that the p15s are granule-associated proteins of PMN. Both purified isoforms bind avidly to lipopolysaccharide (LPS), the major component of the Gram-negative bacterial outer membrane. Analysis of the deduced primary structures of the p15s reveals homology to three other leukocyte proteins: CAP-18, an 18-kDa LPS-binding protein from rabbit PMN, pro indolicidin, a 16-kDa precursor of an antibacterial peptide of bovine PMN, and cathelin, an 11-kDa cysteine protease inhibitor from porcine leukocytes, suggesting the existence of a novel family of leukocyte proteins with LPS binding, antimicrobial, and protease-inhibitory activities. PMID- 8449964 TI - The lysine-49 phospholipase A2 from the venom of Agkistrodon piscivorus piscivorus. Relation of structure and function to other phospholipases A2. PMID- 8449965 TI - Effect of cisplatin on primary tumour growth and liver metastases in the M 5076 reticulum sarcoma: implication for new screening modalities. AB - We investigated the effect of cisplatin given at different treatment intervals on growth of the s.c.-implanted M 5076 reticulum sarcoma and the number of liver metastases at the end of the experiment (day 24). The later the treatment was started, the smaller was the tumour-inhibiting effect of cisplatin on primary tumour growth. Initiation of cisplatin treatment before day 14 after tumour implantation inhibited liver metastases completely. Treatment starting from day 14 or later did not influence the number of liver metastases. With regard to the clinical situation, the data imply that in the search for new leads in anticancer compounds, experimental conditions should concentrate on the inhibition of metastatic tumour growth. PMID- 8449966 TI - Methotrexate cytotoxicity determination using the MTT assay following enzymatic depletion of thymidine and hypoxanthine. AB - Methotrexate, an important agent in the treatment of childhood acute lymphoblastic leukaemia, has generally failed to induce dose-dependent cytotoxicity of patient-derived leukaemic blasts when tested in the 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. This effect is apparently due to salvage from the medium, by surviving leukaemic cells, of metabolites such as hypoxanthine and thymidine. In an attempt to address this problem, we have examined the effect, on leukaemic cell populations, of enzymatically depleting these metabolites from the culture medium employed during the MTT assay, using xanthine oxidase and thymidine phosphorylase. Specifically we have assessed methotrexate cytotoxicity in the paediatric acute lymphoblastic T cell leukaemia, GKTL, which is maintained as a xenograft, and like primary leukaemias, has poor viability in vitro. Although little cytotoxicity of GKTL cells was observed when the MTT assay was performed in supplemented RPMI-1640 medium, dose-dependent cytotoxicity of these cells was clearly apparent when the same medium was enzymatically depleted. In contrast, the ID50 for methotrexate of control CCRF-CEM cells was unaltered in enzymatically depleted medium. In the absence of methotrexate, enzymatic depletion of the medium did not affect leukaemic cell survival. We are currently investigating the general applicability of this approach for assaying the response to methotrexate of primary leukaemia samples. PMID- 8449967 TI - Second-look laparotomies in ovarian cancer: a medical oncologist's perspective. PMID- 8449968 TI - Contributions of nuclear medicine to the therapy of malignant tumors. AB - Radionuclides are applied in oncology for diagnosis and therapy. The former demands gamma--emitting radionuclides for labeling specific substrates for localizing malignant tissue and for analyzing tumor metabolism in vivo. Here, positron emission tomography (PET) may register in vivo the metabolism, for example, of glucose, amino acids, and receptors and of potentially useful cytotoxic agents. The advantage of the positron emitting radionuclides of carbon, nitrogen and fluorine is the labeling of substrates without changing substrate specificity within the metabolic reaction chain; also, substrate concentration in situ may be quantified. With regard to therapy radionuclides that emit beta- and alpha-particles or decay by electron capture with the Auger effect, are administered in ionic form or with tumor seeking substrates. Examples are radioiodine for treating thyroid malignancy and radiophosphorus for myeloproliferative diseases. Organically bound radionuclides are given as labeled ligands for specific receptors, such as meta-iodo-benzylguanidine (MIBG) for treating the catecholamine producing tumors phaeochromocytoma and neuroblastoma and labeled monoclonal antibodies for tumors specific receptors. Highly localized energy depositions come from Auger emitters such as 125I and by the neutron capture therapy, where boron-10 in the tumor cell is exposed to thermal neutrons for initiating the B10 (n; alpha) Li7 reaction, especially for treating neuro- and glioblastoma and melanoma. Endogenous radiotherapy with radionuclides rely on the success of delivering a proper amount of energy into individual tumor cells with optimal protection of normal tissue. The inevitable heterogeneity of energy deposition events from such approaches demands careful dosimetric assessment for which the classical methods of dosimetry for percutaneous radiotherapy are not applicable. PMID- 8449969 TI - Tumors in rat kidney generated by initiation with trans-4-acetylaminostilbene and several promoting treatments. AB - trans-4-Acetylaminostilbene (AAS) is a complete carcinogen in rats and produces quite selectively tumors in Zymbal's glands. On the basis of DNA adduct formation, it has been proposed that this model arylamine initiates neoplastic transformation of cells in many tissues, particularly liver and kidney, which, in the classical sense are considered to be non-target tissues for this chemical. In the present study an initiating treatment with AAS was followed by unilateral nephrectomy and the application of two nephrotoxic substances, gentamycin or beta cyclodextrin which, among other activities, stimulate cell proliferation specifically in kidney. The initiating dose of AAS, given alone, gave rise to Zymbal's gland and mammary tumors in female Wistar rats within 88 weeks but not to liver or kidney tumors. When the initiation treatment was followed by unilateral nephrectomy, alone or in combination with gentamycin, or by beta cyclodextrin, four tumors in two out of ten animals, eight tumors in three/ten, and seven tumors in three/ten, respectively, were observed in the kidney. The administered dose of gentamycin was not sufficient to induce tumors on its own. The results support the view that the genotoxic effects of AAS produce promotable lesions in rat kidney. None of the animals that had been treated with AAS, with or without other treatments, developed tumors or the predominant types of preneoplastic lesions in the liver within 88 weeks; this supports the notion that liver, like kidney, is not a target for complete carcinogenesis for this chemical. PMID- 8449970 TI - Differentiation of the rat myelomonocytic leukemia cell line c-WRT-7 by in vitro culture with the rat bone marrow preadipocyte cell line REC A16. AB - Differentiation of the rat myelomonocytic leukemia cell line (c-WRT-7) was investigated, by co-culture with a rat embryonic bone marrow preadipose cell line (REC A16). Co-cultivation with REC A16, or with conditioned medium from REC A16 cultures (REC-CM), induced differentiation of c-WRT-7 cells to macrophages. A soluble factor(s) produced by REC A16 appeared to be responsible for the differentiation of c-WRT-7. Because REC-CM was associated with colony-stimulating activity on murine marrow progenitors, c-WRT-7 cells were cultured with various colony-stimulating factors (CSF) and it was found that macrophage CSF (M-CSF) significantly induced differentiation of c-WRT-7. We further demonstrated that both the colony-stimulating and differentiation-inducing activities of REC-CM were significantly blocked by anti-M-CSF antiserum. These results suggest that the differentiation of c-WRT-7 is due to M-CSF produced by REC A16. Co-culture of these two cell lines should provide a useful model to study the mechanisms of interaction between leukemia cells and marrow stroma. PMID- 8449971 TI - Monoclonal antibody accumulation in experimental and spontaneous lung metastases of human malignant melanoma in rodents. AB - Monoclonal antibody (mAb) uptake in metastatic lung lesions was depicted and evaluated by digital autoradiography. The models examined were experimental metastases of a human melanoma in nude mice and spontaneous metastases of human melanoma in immunocompromised young rats. By comparing uptake patterns in local (s.c.) tumours and in lung processes of various sizes it was found that patterns were essentially similar in both types of malignant tissue. From the point of view of visualization, however, the high blood content of lung tissue resulted in high background and low contrast. This could be overcome by the use of rapidly cleared antibody fragments. PMID- 8449972 TI - Radioprotective effect of N-acetylcysteine on granulocyte/macrophage colony forming cells of human bone marrow. AB - N-Acetylcysteine, known as a radical scavenger, was examined for its influence on the radiotolerance of progenitor cells of granulocytopoiesis. Added before and after irradiation in a dose of 2 mg/ml to suspension cultures of non-adherent low density human bone marrow cells N-acetylcysteine (AcCys) clearly improved the survival. The D0 value of the survival curve for granulocyte/macrophage colony forming cells increased by a factor of 1.56 as compared to non-treated control suspensions. The improvement of radiation tolerance is probably not only based on the radical scavenger properties (radioprotective component) of AcCys, but also on the support of repair processes. PMID- 8449974 TI - Report from the 28th Annual Meeting of the American Society of Clinical Oncology. 17-19 May 1992. PMID- 8449973 TI - Borderline chondrosarcoma of long and flat bones. AB - We reviewed histological and clinical findings of six cases of borderline chondrosarcoma and examined the expression of collagen types I, II, III, V, and VI by immunohistochemical analysis of these tumors. Borderline chondrosarcoma is defined as a cartilaginous tumor of bone resembling enchondroma on the basis of histomorphology. Clinically the tumor causes intermittent vague pain unrelated to physical activities. On radiographs borderline chondrosarcoma is characterized by evidence of endosteal erosion. We observed local recurrences in two cases treated by intralesional excision and marginal excision, and one of those cases died of inoperable local tumor recurrence. In our histological analysis based on tissue patterns, there were enchondromatous patterns in five cases, and chondrosarcomatous patterns in four cases. In the second recurrent tumor in one case, a chondrosarcomatous pattern was newly observed, and the recurrent tumor was found to be a low-grade chondrosarcoma cytologically in the other case. In the tumor matrix immunoreactivity for collagen types II and VI was predominant, with collagen types I, III, and V showing heterogeneous expression in some cases. In all cases rimming of tumor lobules with collagen types I and V was absent. Immunoreactivity for collagen type II in the cytoplasm of tumor cells was found in four cases and all three recurrent tumors. Borderline chondrosarcoma, as defined by histology, clinical symptoms and radiological appearance, shows a collagen distribution pattern similar to that of low-grade chondrosarcoma. These findings are in accordance with the clinical outcome of borderline chondrosarcoma which parallels that of low-grade chondrosarcoma. Thus borderline chondrosarcoma may be best treated by wide en-bloc excision rather than curettage. PMID- 8449975 TI - 3rd Indo-German Workshop on Recent Results in Cooperative Cancer Research. PMID- 8449976 TI - XX. Meeting of the European Tumor Virus Group (ETVG). Scientific proceedings. Insbruck, Austria. March 3-7, 1993. Abstracts. PMID- 8449977 TI - Phosphorylation on protein kinase C sites inhibits nuclear import of lamin B2. AB - The nuclear lamina is a karyoskeletal structure at the nucleoplasmic surface of the inner nuclear membrane. Its assembly state is regulated by phosphorylation of the intermediate filament type lamin proteins. Strong evidence has been obtained for a causal link between phosphorylation of lamins by the p34cdc2 protein kinase and disassembly of the nuclear lamina during mitosis. In contrast, no information is currently available on the role of lamin phosphorylation during interphase of the cell cycle. Here, we have identified four protein kinase C phosphorylation sites in purified chicken lamin B2 as serines 400, 404, 410, and 411. In vivo, the tryptic peptide containing serines 400 and 404 is phosphorylated throughout interphase, whereas serines 410 and 411 become phosphorylated specifically in response to activation of protein kinase C by phorbol ester. Prompted by the close proximity of serines 410/411 to the nuclear localization signal of lamin B2, we have studied the influence of phosphorylation of these residues on nuclear transport. Using an in vitro assay, we show that phosphorylation of lamin B2 by protein kinase C strongly inhibits transport to the nucleus. Moreover, phorbol ester treatment of intact cells leads to a substantial reduction of the rate of nuclear import of newly synthesized lamin B2 in vivo. These findings have implications for the dynamic structure of the nuclear lamina, and they suggest that the modulation of nuclear transport rates by cytoplasmic phosphorylation may represent a general mechanism for regulating nuclear activities. PMID- 8449978 TI - Morphogenesis in the yeast cell cycle: regulation by Cdc28 and cyclins. AB - Analysis of cell cycle regulation in the budding yeast Saccharomyces cerevisiae has shown that a central regulatory protein kinase, Cdc28, undergoes changes in activity through the cell cycle by associating with distinct groups of cyclins that accumulate at different times. The various cyclin/Cdc28 complexes control different aspects of cell cycle progression, including the commitment step known as START and mitosis. We found that altering the activity of Cdc28 had profound effects on morphogenesis during the yeast cell cycle. Our results suggest that activation of Cdc28 by G1 cyclins (Cln1, Cln2, or Cln3) in unbudded G1 cells triggers polarization of the cortical actin cytoskeleton to a specialized pre-bud site at one end of the cell, while activation of Cdc28 by mitotic cyclins (Clb1 or Clb2) in budded G2 cells causes depolarization of the cortical actin cytoskeleton and secretory apparatus. Inactivation of Cdc28 following cyclin destruction in mitosis triggers redistribution of cortical actin structures to the neck region for cytokinesis. In the case of pre-bud site assembly following START, we found that the actin rearrangement could be triggered by Cln/Cdc28 activation in the absence of de novo protein synthesis, suggesting that the kinase may directly phosphorylate substrates (such as actin-binding proteins) that regulate actin distribution in cells. PMID- 8449979 TI - Effect of caffeine and reduced temperature (20 degrees C) on the organization of the pre-Golgi and the Golgi stack membranes. AB - In the present study we have dissected the transport pathways between the ER and the Golgi complex using a recently introduced (Kuismanen, E., J. Jantti, V. Makiranta, and M. Sariola. 1992. J. Cell Sci. 102:505-513) inhibition of transport by caffeine at 20 degrees C. Recovery of the Golgi complex from brefeldin A (BFA) treatment was inhibited by caffeine at reduced temperature (20 degrees C) suggesting that caffeine inhibits the membrane traffic between the ER and the Golgi complex. Caffeine at 20 degrees C did not inhibit the BFA-induced retrograde movement of the Golgi membranes. Further, incubation of the cells in 10 mM caffeine at 20 degrees C had profound effects on the distribution and the organization of the pre-Golgi and the Golgi stack membranes. Caffeine treatment at 20 degrees C resulted in a selective and reversible translocation of the pre- and cis-Golgi marker protein (p58) to the periphery of the cell. This caffeine induced effect on the Golgi complex was different from that induced by BFA, since mannosidase II, a Golgi stack marker, remained perinuclearly located and the Golgi stack coat protein, beta-COP, was not detached from Golgi membranes in the presence of 10 mM caffeine at 20 degrees C. Electron microscopic analysis showed that, in the presence of caffeine at 20 degrees C, the morphology of the Golgi stack was altered and accumulation of numerous small vesicles in the Golgi region was observed. The results in the present study suggest that caffeine at reduced temperature (20 degrees C) reveals a functional interface between the pre-Golgi and the Golgi stack. PMID- 8449980 TI - Polarity and reorganization of the endoplasmic reticulum during fertilization and ooplasmic segregation in the ascidian egg. AB - During the first cell cycle of the ascidian egg, two phases of ooplasmic segregation create distinct cytoplasmic domains that are crucial for later development. We recently defined a domain enriched in ER in the vegetal region of Phallusia mammillata eggs. To explore the possible physiological and developmental function of this ER domain, we here investigate its organization and fate by labeling the ER network in vivo with DiIC16(3), and observing its distribution before and after fertilization in the living egg. In unfertilized eggs, the ER-rich vegetal cortex is overlaid by the ER-poor but mitochondria-rich subcortical myoplasm. Fertilization results in striking rearrangements of the ER network. First, ER accumulates at the vegetal-contraction pole as a thick layer between the plasma membrane and the myoplasm. This accompanies the relocation of the myoplasm toward that region during the first phase of ooplasmic segregation. In other parts of the cytoplasm, ER becomes progressively redistributed into ER rich and ER-poor microdomains. As the sperm aster grows, ER accumulates in its centrosomal area and along its astral rays. During the second phase of ooplasmic segregation, which takes place once meiosis is completed, the concentrated ER domain at the vegetal-contraction pole moves with the sperm aster and the bulk of the myoplasm toward the future posterior side of the embryo. These results show that after fertilization, ER first accumulates in the vegetal area from which repetitive calcium waves are known to originate (Speksnijder, J. E. 1992. Dev. Biol. 153:259-271). This ER domain subsequently colocalizes with the myoplasm to the presumptive primary muscle cell region. PMID- 8449981 TI - Apical secretion of apolipoproteins from enterocytes. AB - Synthesis and secretion of apolipoproteins in pig small intestine was studied by pulse-chase labeling of jejunal segments, kept in organ culture. Apo A-1 and apo B-48 were the two major proteins released, constituting 25 and 10%, respectively, of the total amount of labeled protein in the mucosal-side medium where they appeared with a t1/2 of 50-60 min. Using tissue from fasting animals, > 85% of newly synthesized apo A-1 and about one third of apo B-48 was released to the mucosal-side medium. Newly synthesized apolipoprotein that remained associated with the intestinal segment accumulated in the soluble fraction, suggesting a basolateral secretion into the intercellular space, and both this accumulation and the release to the medium was prevented by culture at 20 degrees C. The specific radioactivity of apo A-1 and apo B-48 released to the medium was significantly higher than that of the corresponding apolipoproteins remaining associated with the intestinal tissue. Furthermore, during culture periods of up to 5 h, the enterocytes and their tight junctions largely remained intact as evidenced by the inaccessibility of the nonpermeable surface marker Ruthenium red. We therefore propose that enterocytes release most of their newly made free apo A-1 and a significant portion of apo B-48 by exocytosis via the brush border membrane into the intestinal lumen. Fat absorption reduced apolipoprotein secretion to the medium and induced the formation of chylomicrons, containing apo A-1 at their surface, as evidenced by immunogold electron microscopy. The chylomicrons were localized in the Golgi complex and near the basolateral plasma membrane, but not in the apical region of the enterocytes, indicating that only free apolipoproteins are secreted to the intestinal lumen. PMID- 8449983 TI - Endothelial cell cytosolic free calcium regulates neutrophil migration across monolayers of endothelial cells. AB - Polymorphonuclear leukocytes (PMN) traverse an endothelial cell (EC) barrier by crawling between neighboring EC. Whether EC regulate the integrity of their intercellular adhesive and junctional contacts in response to chemotaxing PMN is unresolved. EC respond to the binding of soluble mediators such as histamine by increasing their cytosolic free calcium concentration ([Ca++]i) (Rotrosen, D., and J.I. Gallin. 1986. J. Cell Biol. 103:2379-2387) and undergoing shape changes (Majno, G., S. M. Shea, and M. Leventhal. 1969. J. Cell Biol. 42:617-672). Substances such as leukotriene C4 (LTC4) and thrombin, which increased the permeability of EC monolayers to ions, as measured by the electrical resistance of the monolayers, transiently increased EC [Ca++]i. To determine whether chemotaxing PMN cause similar changes in EC [Ca++]i, human umbilical vein endothelial cells (HUVEC) maintained as monolayers were loaded with fura-2. [Ca++]i was measured in single EC during PMN adhesion to and migration across these monolayers. PMN-EC adhesion and transendothelial PMN migration in response to formyl-methionyl-leucyl-phenylalanine (fMLP) as well as to interleukin 1 (IL 1) treated EC induced a transient increase in EC [Ca++]i which temporally corresponded with the time course of PMN-EC interactions. When EC [Ca++]i was clamped at resting levels with a cell permeant calcium buffer, PMN migration across EC monolayers and PMN induced changes in EC monolayer permeability were inhibited. However, clamping of EC [Ca++]i did not inhibit PMN-EC adhesion. These studies provide evidence that EC respond to stimulated PMN by increasing their [Ca++]i and that this increase in [Ca++]i causes an increase in EC monolayer permeability. Such [Ca++]i increases are required for PMN transit across an EC barrier. We suggest EC [Ca++]i regulates transendothelial migration of PMN by participating in a signal cascade which stimulates EC to open their intercellular junctions to allow transendothelial passage of leukocytes. PMID- 8449982 TI - Annexin II is a major component of fusogenic endosomal vesicles. AB - We have used an in vitro assay to follow the proteins transferred from a donor to an acceptor upon fusion of early endosomes. The acceptor was a purified early endosomal fraction immunoisolated on beads and the donor was a metabolically labeled early endosomal fraction in suspension. In the assay, both fractions were mixed in the presence of unlabeled cytosol, and then the beads were retrieved and washed. The donor proteins transferred to the acceptor were identified by two dimensional gel electrophoresis and autoradiography. Approximately 50 major proteins were transferred and this transfer fulfilled all criteria established for endosome fusion in vitro. However, only a small subset of proteins was efficiently transferred, if donor endosomes were briefly sonicated to generate small (0.1 micron diam) vesicles before the assay. These include two acidic membrane proteins, and three alkaline peripheral proteins exposed on the cytoplasmic face of the membrane. Partial sequencing and Western blotting indicated that one of the latter components is annexin II, a protein known to mediate membrane-membrane interactions. Immunogold labeling of cryosections confirmed that annexin II is present on early endosomes in vivo. These data demonstrate that annexin II, together with the other four proteins we have identified, is a major component of fusogenic endosomal vesicles, suggesting that these proteins are involved in the binding and/or fusion process. PMID- 8449984 TI - Relative distribution of actin, myosin I, and myosin II during the wound healing response of fibroblasts. AB - Myosin I is present in Swiss 3T3 fibroblasts and its localization reflects a possible involvement in the extension and/or retraction of protrusions at the leading edge of locomoting cells and the transport of vesicles, but not in the contraction of stress fibers or transverse fibers. An affinity-purified polyclonal antibody to brush border myosin I colocalizes with a polypeptide of 120 kD in fibroblast extracts. Within initial protrusions of polarized, migrating fibroblasts, myosin I exhibits a punctate distribution, whereas actin is diffuse and myosin II is absent. Myosin I also exists in linear arrays parallel to the direction of migration in filopodia and microspikes, established protrusions, and within the leading lamellae of migrating cells. Myosin II and actin colocalize along transverse fibers in the lamellae of migrating cells, while myosin I displays no definitive organization along these fibers. During contractions of actin-based fibers, myosin II is concentrated in the center of the cell, while the distribution of myosin I does not change. Thus, myosin I is found at the correct location and time to be involved in the extension and/or retraction of protrusions and the transport of vesicles. Myosin II-based contractions in more posterior cellular regions could generate forces to separate cells, maintain a polarized cell shape, maintain the direction of locomotion, maximize the rate of locomotion, and/or aid in the delivery of cytoskeletal/contractile subunits to the leading edge. PMID- 8449985 TI - Identification, characterization and cloning of myr 1, a mammalian myosin-I. AB - We have identified, characterized and cloned a novel mammalian myosin-I motor molecule, called myr 1 (myosin-I from rat). Myr 1 exists in three alternative splice forms: myr 1a, myr 1b, and myr 1c. These splice forms differ in their numbers of putative calmodulin/light chain binding sites. Myr 1a-c were selectively released by ATP, bound in a nucleotide-dependent manner to F-actin and exhibited amino acid sequences characteristic of myosin-I motor domains. In addition to the motor domain, they contained a regulatory domain with up to six putative calmodulin/light chain binding sites and a tail domain. The tail domain exhibited 47% amino acid sequence identity to the brush border myosin-I tail domain, demonstrating that myr 1 is related to the only other mammalian myosin-I motor molecule that has been characterized so far. In contrast to brush border myosin-I which is expressed in mature enterocytes, myr 1 splice forms were differentially expressed in all tested tissues. Therefore, myr 1 is the first mammalian myosin-I motor molecule with a widespread tissue distribution in neonatal and adult tissues. The myr 1a splice form was preferentially expressed in neuronal tissues. Its expression was developmentally regulated during rat forebrain ontogeny and subcellular fractionation revealed an enrichment in purified growth cone particles, data consistent with a role for myr 1a in neuronal development. PMID- 8449986 TI - Mammalian myosin I alpha, I beta, and I gamma: new widely expressed genes of the myosin I family. AB - A polymerase chain reaction strategy was devised to identify new members of the mammalian myosin I family of actin-based motors. Using cellular RNA from mouse granular neurons and PC12 cells, we have cloned and sequenced three 1.2-kb polymerase chain reaction products that correspond to novel mammalian myosin I genes designated MMI alpha, MMI beta, MMI gamma. The pattern of expression for each of the myosin I's is unique: messages are detected in diverse tissues including the brain, lung, kidney, liver, intestine, and adrenal gland. Overlapping clones representing full-length cDNAs for MMI alpha were obtained from mouse brain. These encode a 1,079 amino acid protein containing a myosin head, a domain with five calmodulin binding sites, and a positively charged COOH terminal tail. In situ hybridization reveals that MMI alpha is highly expressed in virtually all neurons (but not glia) in the postnatal and adult mouse brain and in neuroblasts of the cerebellar external granular layer. Expression varies in different brain regions and undergoes developmental regulation. Myosin I's are present in diverse organisms from protozoa to vertebrates. This and the expression of three novel members of this family in brain and other mammalian tissues suggests that they may participate in critical and fundamental cellular processes. PMID- 8449987 TI - The transport properties of axonal microtubules establish their polarity orientation. AB - It is well established that axonal microtubules (MTs) are uniformly oriented with their plus ends distal to the neuronal cell body (Heidemann, S. R., J. M. Landers, and M. A. Hamborg. 1981. J. Cell Biol. 91:661-665). However, the mechanisms by which these MTs achieve their uniform polarity orientation are unknown. Current models for axon growth differ with regard to the contributions of MT assembly and transport to the organization and elaboration of the axonal MT array. Do the transport properties or assembly properties of axonal MTs determine their polarity orientation? To distinguish between these possibilities, we wished to study the initiation and outgrowth of axons under conditions that would arrest MT assembly while maintaining substantial levels of preexisting polymer in the cell body that could still be transported into the axon. We found that we could accomplish this by culturing rat sympathetic neurons in the presence of nanomolar levels of vinblastine. In concentrations of the drug up to and including 100 nM, the neurons actively extend axons. The vinblastine-axons are shorter than control axons, but clearly contain MTs. To quantify the effects of the drug on MT mass, we compared the levels of polymer throughout the cell bodies and axons of neurons cultured overnight in the presence of 0, 16, and 50 nM vinblastine with the levels of MT polymer in freshly plated neurons before axon outgrowth. Without drug, the total levels of polymer increase by roughly twofold. At 16 nM vinblastine, the levels of polymer are roughly equal to the levels in freshly plated neurons, while at 50 nM, the levels of polymer are reduced by about half this amount. Thus, 16 nM vinblastine acts as a "kinetic stabilizer" of MTs, while 50 nM results in some net MT disassembly. At both drug concentrations, there is a progressive increase in the levels of MT polymer in the axons as they grow, and a corresponding depletion of polymer from the cell body. These results indicate that highly efficient mechanisms exist in the neuron to transport preassembled MTs from the cell body into the axon. These mechanisms are active even at the expense of the cell body, and even under conditions that promote some MT disassembly in the neuron. MT polarity analyses indicate that the MTs within the vinblastine-axons, like those in control axons, are uniformly plus-end distal.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8449989 TI - Evidence that activation of platelet calpain is induced as a consequence of binding of adhesive ligand to the integrin, glycoprotein IIb-IIIa. AB - Calpain (a Ca(2+)-dependent protease) is present in many cell types. Because it is present in the cytosol, the potential exists that it may regulate critical intracellular events by inducing crucial proteolytic cleavages. However, the concentrations of Ca2+ required to activate calpain are higher than those attained in the cytoplasm of most cells. Thus, the physiological importance of calpain and the mechanisms involved in its activation have remained elusive. In this study, we show that calpain rapidly moved to a peripheral location upon the addition of an agonist to suspensions of platelets, but it remained unactivated. We provide three lines of evidence that calpain was subsequently activated by a mechanism that required the binding of an adhesive ligand to the major platelet integrin, glycoprotein (GP) IIb-IIIa: calpain activation was prevented by RGDS, a tetrapeptide that inhibits the binding of adhesive ligand to GP IIb-IIIa; it was also prevented by monoclonal antibodies that inhibit adhesive ligand binding to GP IIb-IIIa; and its activation was markedly reduced in platelets from patients whose platelets have greatly reduced levels of functional GP IIb-IIIa. Thus, in platelets, binding of the extracellular domain of GP IIb-IIIa to its adhesive ligand can initiate a transmembrane signal that activates intracellular calpain. Because calpain is present in focal contacts of adherent cells, the interaction of integrins with adhesive ligands in the extracellular matrix may regulate activation of calpain in other cell types as well. PMID- 8449988 TI - Depletion of intracellular potassium disrupts coated pits and reversibly inhibits cell polarization during fibroblast spreading. AB - To learn more about the possible role of the coated pits endocytic pathway in cell adhesion, we studied attachment and spreading of fibroblasts whose coated pits were disrupted by depletion of intercellular potassium. Fibroblasts incubated in suspension in potassium-free medium lost 80% of their intracellular potassium within 10 min and showed disrupted coated pits based on fluorescence staining of clathrin. Potassium-depleted cells attached and spread on fibronectin coated substrata over the same time course (15 min-2 h) as control cells. Unlike controls, however, potassium-depleted fibroblasts attained a radial morphology with circumferentially organized actin filament bundles and were unable to make the transition to a polarized morphology with stress fibers. In the radially spread fibroblasts, fibronectin receptors and vinculin colocalized in focal adhesion sites and appeared to be membrane insertion points for circumferentially arranged actin filament bundles, but these sites were much smaller than the focal adhesion plaques in polarized cells. The effects of potassium depletion on cell adhesion were reversible. Within 1 h after switching K(+)-depleted fibroblasts to medium containing KCl, cells developed a polarized morphology with actin stress fibers inserting into focal adhesion plaques. Coated pits also reformed on the cell surface during this time. Because formation of focal adhesion plaques preceded reappearance of clathrin-coated pits at the cell margins, it seems unlikely that coated pits play a direct role in adhesion plaque assembly. Polarization of fibroblasts upon addition of KCl was inhibited by ouabain showing that intracellular potassium was required for activity. Polarization also was inhibited when potassium-depleted cells were switched to potassium-containing medium under hypertonic or acidified conditions, both of which have been shown to inhibit receptor-mediated endocytosis. Our results suggest that the coated pit endocytic pathway is not required for initial attachment, spreading, and formation of focal adhesions by fibroblasts, but may play a role in cell polarization. PMID- 8449990 TI - Thermotolerance in mammalian cells. Protein denaturation and aggregation, and stress proteins. AB - Cells that have been pre-exposed to thermal stress can acquire a transient resistance against the killing effect of a subsequent thermal stress. The cause for this phenomenon, called thermotolerance, seems to be an enhanced resistance of proteins against thermal denaturation and aggregation. This resistance can be expressed as an attenuation of damage formation (less initial damage) or as a better repair of the protein damage (facilitated recovery). Heat Shock (or better, Stress) Proteins (HSPs) may play a role in and even be required for thermal resistance. However, rather than stress-induced enhanced synthesis and elevated total levels of HSPs per se, the concentration of, both constitutive and inducible, HSPs at and/or (re)distributed to specific subcellular sites may be the most important factor for the acquisition of thermotolerance. Specific HSPs may be involved either in damage protection or in damage repair. PMID- 8449991 TI - A survey of interactions made by the giant protein titin. AB - A simple solid-phase binding assay was used to screen for interactions that the giant myofibrillar protein titin makes with other sarcomeric proteins. The titin used in the tests was purified by a modified procedure that results in isolation of approximately 20 mg relatively undegraded protein in < 24 h. In addition to the approximately 3 MDa polypeptide, bands at approximately 160 kDa and approximately 100 kDa were also consistently seen on gels. Binding of titin to myosin, C-protein, X-protein and AMP-deaminase was observed. The interaction with myosin appears to be with the light meromyosin part of the molecule. PMID- 8449992 TI - Microinjection of a monoclonal antibody against SPN antigen, now identified by peptide sequences as the NuMA protein, induces micronuclei in PtK2 cells. AB - Several high molecular mass proteins which relocate from the interphase nucleus to the spindle poles during mitosis have been defined by antibodies. Microinjection experiments have shown that at least the antigen defined by SPN antibody plays a functional role during mitosis. Recently the cDNA sequence for human NuMA antigen was established and epitopes for antibodies to centrophilin, and to 1F1 and 1H1 antigens were found to be included in the NuMA protein. Here we show that immunoprecipitated SPN antigen reacts with an autoimmune human NuMA serum. In addition three peptides derived from immunoprecipitated human SPN by cyanogen bromide cleavage and covering more than fifty amino acids show a perfect fit with the sequence predicted for NuMA protein. Thus SPN antigen and NuMA are the same protein. Injection of SPN-3 antibody into interphase or mitotic PtK2 cells results in cells with micronuclei. For cells injected in prophase, prometaphase or metaphase 90%, 78% and 77% display defective cytokinesis or yield daughter cells with micronuclei. In contrast only 16% of cells injected in anaphase are abnormal. Thus SPN/NuMA antigen may be required during early, but not during later, stages of mitosis. Surprising parallels are seen between the effects of microinjecting SPN-3 antibody and treatment with colcemid and taxol of PtK2 and HeLa cells. Our results identify an important role during mitosis for the SPN/NuMA antigen. PMID- 8449993 TI - Lytic granules from cytotoxic T cells exhibit kinesin-dependent motility on microtubules in vitro. AB - One major mechanism of cell-mediated cytolysis is the polarized secretion of lytic granules, a process which is highly dependent on microtubules. We isolated lytic granules from murine cytotoxic T cells and tested their ability to bind to and move along microtubules in vitro. In the presence of a motor-containing supernatant, the granules bound to the microtubules and moved along them at an average maximal rate of 1 microns/second. Virtually every granule could bind to microtubules, and about half translocated within a few seconds of binding. Motility required exogenous cytosolic motors, hydrolyzable nucleotides, and an intact granule membrane. Although the motor preparation used to support granule movement contains both plus- and minus-end-directed motor proteins, granule movement was strongly biased toward microtubule plus-ends. Inactivation of cytoplasmic dynein had little effect on granule binding and movement, but immuno depletion of kinesin from the motor preparation inhibited granule binding by 50%. These results indicate that most granule movement in this assay is mediated by kinesin. The speed and direction of granule movement in vitro are sufficient to account for the release of lytic granules in the intact T cell. This model system should be valuable for studying the interactions of secretory granules with microtubules, and for identifying the regulatory factors involved. PMID- 8449994 TI - Proteases are not involved in the membrane fusion events of the lysolecithin mediated guinea pig sperm acrosome reaction. AB - The guinea pig sperm acrosome reaction is characterized by a complex temporal and structural pattern of membrane fusions. In this study, we have used specific protease inhibitors to determine if proteases regulate this pattern of membrane fusions during the lysolecithin-mediated guinea pig sperm acrosome reaction. Inhibitors were chosen so as to cover a wide range of different types of proteases, and all were used at the highest concentration that did not adversely affect sperm motility. Of the eight inhibitors tested, leupeptin, soya bean trypsin inhibitor (SBTI), p-aminobenzamidine (pAB) and nitrophenyl p'-guanidino benzoate (NPGB) inhibited completion of the acrosome reaction, while diethylenetriaminepentaacetic acid (DTPA), phosphoramidon, bestatin and pepstatin had no effect. Sperm that had been acrosome-reacted in the presence of each inhibitor were examined by transmission electron microscopy to assess whether the inhibitors altered the pattern of membrane fusions during the acrosome reaction. DTPA, phosphoramidon, bestatin and pepstatin had no effect on membrane fusion or matrix dispersal. Serine protease inhibitors such as leupeptin, SBTI, pAB and NPGB prevented complete dispersal of the acrosomal matrix and completion of the acrosome reaction, but did not alter the temporal sequence or structural pattern of membrane fusions. The undispersed matrix was present along the dorsal and ventral aspects of the apical segment and throughout the principal segment. We conclude that proteases are not involved in regulating the temporal and structural pattern of membrane fusions which occurs during the lysolecithin mediated acrosome reaction of guinea pig sperm. PMID- 8449995 TI - Haemopoietic stem cell development to neutrophils is associated with subcellular redistribution and differential expression of protein kinase C subspecies. AB - Multipotential FDCP-Mix A4 (A4) cells can be induced either to self-renew or to differentiate and develop into mature neutrophils in liquid culture, depending on the haemopoietic growth factors with which they are cultured. When cultured in low concentrations of interleukin 3 (IL-3, 1 unit/ml)) plus Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) and Granulocyte-CSF (G-CSF), A4 cells proliferate with accompanying development to form cells which resemble mature, postmitotic neutrophils. The presence of high concentrations of IL-3 (100 units/ml) blocks the development of A4 cells even in the presence of GM-CSF plus G-CSF. A4 cell development to neutrophils is accompanied by major changes in the expression of protein kinase C (PKC) subspecies in these cells. The predominant subspecies present in multipotent A4 cells, as judged by direct chromatographic analysis, was the type III enzyme (alpha) subspecies, whereas in mature A4 cell neutrophils, the type II (beta I + beta II) enzymes were predominant. Phorbol esters added to immature A4 cells resulted in a proliferative response, but when added to postmitotic A4 cells resembling neutrophils they elicited a large increase in reactive oxygen intermediate production. This suggests that the type III (alpha) subspecies may mediate proliferative responses in stem cells, whilst the type II (beta I + beta II) enzymes are more important for the mature cell functions of postmitotic neutrophils. In cultures containing IL-3 (100 units/ml) both the type III, and also the type II subspecies were predominantly membrane associated for prolonged periods (> 24 hours).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8449996 TI - The gene encoding the calcium binding protein calcyclin is expressed at sites of exocytosis in the mouse. AB - Calcyclin is a member of the S100 family of calcium binding proteins. We have found by in situ hybridization that calcyclin transcripts are restricted to specific cell types within a limited number of mouse organs. High levels of expression in the epithelia lining the gastrointestinal, respiratory and urinary tracts, and specific localization of the transcripts to the goblet cells in the small intestine, lead us to suggest a role for calcyclin in the process of mucus secretion. In addition, calcyclin expression was detected in the corpus luteum, placenta and nerves within the gut wall, which are all sites of regulated exocytosis. We propose that this S100-like protein may be part of a calcium signalling pathway utilized in the secretion of various products by different cell types. PMID- 8449997 TI - cDNA-derived molecular characteristics and antibodies to a new centrosome associated and G2/M phase-prevalent protein. AB - Differential screening of a murine RNA-based cDNA library with cell cycle phase specific transcripts released a cDNA clone (lambda CCD41) to a mRNA (1.349 kb) which, according to the mode of its detection, increases as expected during the cell cycle. The molecular characteristics of the protein (27 x 10(3) M(r)) encoded by this mRNA were deduced from the cDNA sequence and antibodies were prepared against the recombinant protein. Immunofluorescence studies performed with PtK2 cells revealed that the amount of the antigen specified by the CCD41 sequence increases during the cell cycle out of proportion with the DNA content. In G1 phase cells, the antigen is exclusively located at the site of the centrosome. During cell cycle progression the antigen becomes also detectable in perinuclear vesicles that increase in number and size, reaching a maximum in G2 phase cells. The centrosomal location of the CCD41 antigen was investigated in relation to another centrosomal antigen, centrosomin A. Since the latter antigen is detected by a monoclonal antibody reacting specifically and permanently with the centrosomes in PtK2 cells throughout the cell cycle it was possible to investigate the relative positions of the two proteins at the site of the centrosome and to add new information about the general architecture of the organelle and its changes during the cell cycle. While the centrosomin A antibody detects the pronounced cell cycle stage-dependent shape changes of the centrosome, the CCD41-encoded protein appears to be localized as a compact structure inside the centrosome. Its epitopes are exposed throughout the cell cycle except during a brief period immediately after the formation of the daughter centrosome. PMID- 8449998 TI - The membrane fusion events in degranulating guinea pig eosinophils. AB - We have investigated the granule fusion events associated with exocytosis in degranulating peritoneal guinea pig eosinophils by time-resolved patch-clamp capacitance measurements using the phase detector technique. Intracellular stimulation with micromolar calcium and GTP gamma S induces a 2- to 3-fold capacitance increase. The main phase of the capacitance increase occurs after a delay of 2-7 minutes and is composed of well-resolved capacitance steps. The number of steps is very close to the number of crystalloid granules contained in a resting cell and the step size distribution with a peak at 9 fF is in excellent agreement with the granule size distribution determined by electron microscopy. The individual granules thus fuse sequentially with the plasma membrane. The stepwise capacitance increase is frequently preceded by an apparently continuous capacitance increase which consists of steps smaller than 4 fF, indicating exocytosis of small vesicles as distinct from crystalloid-containing granules. In some cases the time course of the opening of individual fusion pores could be recorded, and this revealed metastable conductance states below 300 pS but random fluctuations at higher conductance levels. This behaviour suggests that the small fusion pore might be a protein structure similar to an ion channel, which becomes a continuously variable lipid pore at higher conductances. In some cells a significant capacitance decrease was observed which is apparently continuous, suggesting a process of membrane uptake by endocytosis of small vesicles. PMID- 8449999 TI - Human retinal pigment epithelial cells from different donors continuously produce a vascular endothelial cell-stimulating factor into serum-free medium. AB - Mitogenic activities of human retinal pigment epithelial cell-conditioned medium (HRPE-CM) with different effects, such as inhibition, stimulation or no effect, on the proliferation of vascular endothelial cells (EC) in vitro have been reported. In this study, 14 HRPE cell lines were established from normal human eyes. Human umbilical vein endothelial cells (HUVEC) in the early passages were used as target cells to detect the mitogenic activity of HRPE-CM on the growth of vascular EC. Our results confirm that HRPE cells in culture continuously synthesize and secrete HUVEC growth substance(s) into a serum-free medium. The ability of HRPE cell lines to produce this mitogen seem unrelated either to in vivo donor factors or to in vitro cell life span. Using an enzyme-linked immunosorbance assay, we demonstrated that only HRPE cell extract, not HRPE-CM, can be recognized by basic fibroblast growth factor (bFGF)-specific antibody, though identical bioactivities on the growth of HUVEC were found in both preparations. The active component in HRPE-CM was heat- and trypsin-sensitive, and stable at extremes of pH (2.5 to 10.0). In addition, the bioactive molecule could not pass through a M(r) 30,000 cut-off membrane, suggesting that it is a fairly high molecular mass polypeptide. These observations suggest that the EC growth factor in HRPE-CM is distinct from fibroblast growth factors (FGFs). PMID- 8450000 TI - Proliferative behaviour of high-ploidy cells in two murine tumour lines. AB - The presence of high-ploidy cells in malignant tumours has long been documented. However, the biological significance of these cells is not known and there is a great deal of controversy over their proliferative potential. We have analysed the behaviour of these cells in two murine tumour lines, B16F10 melanoma and 3T3A31M angiosarcoma, determining their DNA content by microspectrophotometry and using time-lapse film studies. We have found a discrepancy between the presence of high-ploidy cells in metaphase and the absence of hyperploid telophases. High ploidy metaphases may be aborted (mitotic polyploidization), prolonged in time or evolve in the form of multipolar, generally tripolar, mitoses. Our results suggest that high-ploidy cells are capable of proliferating, despite certain peculiarities in their cell cycle, and constitute a tumour subpopulation whose role in neoplasia merits further study. PMID- 8450001 TI - Basement membrane and interstitial matrix components form separate matrices in heterokaryons of PYS-2 cells and fibroblasts. AB - In order to gain further understanding of the spatial organization of interstitial and basement membrane matrices, we studied the expression of the interstitial matrix protein, fibronectin, and the basement membrane protein, laminin, in heterokaryons formed by the fusion of normal fibroblasts and teratocarcinoma-derived epithelial PYS-2 cells. These heterokaryons showed various distributions of the matrix proteins depending on the proportions of the different parental cell nuclei within the cytoplasm of the cell. Heterokaryons containing equal numbers of fibroblast and PYS-2 cell nuclei showed an abundant laminin matrix subcellularly and only minor amounts of fibronectin matrix at the periphery of the cells. Similar results were obtained in heterokaryons containing an excess of epithelial cell nuclei. In heterokaryons containing an excess of fibroblast nuclei, on the other hand, laminin matrix was reduced and a fibrillar fibronectin matrix was seen also on top of the cell body. The results suggest a gene dosage-type of effect on the expression of these proteins. Furthermore, extracellular laminin and fibronectin matrices did not codistribute around the heterokaryons but the two proteins were assembled into separate structures. The lack of codistribution of fibronectin and laminin matrices in heterokaryons suggests that the molecular interactions, which determine the assembly of basement membrane and interstitial matrices in these cells are highly type specific. Similar mechanisms may also operate in the assembly of extracellular matrices in vivo. PMID- 8450002 TI - Nonsurgical management options in impotence. PMID- 8450003 TI - Rational intervention in von Willebrand's disease. PMID- 8450004 TI - Jaundice in the intensive care unit. PMID- 8450005 TI - Medical aspects of cardiac transplantation. PMID- 8450006 TI - Hemoptysis and altered sensorium in a hemodialysis patient. PMID- 8450007 TI - Zidovudine in early HIV disease. PMID- 8450008 TI - Fimbriated stationary phases for proteins. AB - This paper describes synthetic procedures for preparing fimbriated stationary phases on poly(styrene-divinylbenzene) (PS-DVB) packing materials. The synthesis consists of a five-step procedure in which the order in which the steps are carried out may be varied. These steps are (i) polymerization of monomers to form an amphiphilic copolymer or oligomer, (ii) adsorption of either monomers, or polymer onto the PS-DVB surface, (iii) solvent induction of functional group orientation at the PS-DVB-polymer interface and polymer-water interface, (iv) a cross-linking reaction that forms a hydrophilic surface layer, and (v) derivatization of the surface layer with stationary phase. PMID- 8450009 TI - Selectivity of organic solvents in micellar liquid chromatography of amino acids and peptides. AB - The influence of the type of organic modifiers on retention behavior in micellar liquid chromatography is studied. A group of amino acids and small peptides was used as the test mixture. It is shown that the chromatographic selectivities of 2 propanol, acetonitrile and tetrahydrofuran which belong to three different groups in Snyder's classification, are considerably similar in the presence of micelles for the test mixture. On the other hand, the selectivities of 2-propanol and butanol which belong to the same solvent selectivity group are different for these solutes in the micellar mobile phases. PMID- 8450010 TI - Primary contribution of the injector to carryover of a trace analyte in high performance liquid chromatography. AB - When a low-nanogram amount of N1,N3-bis-(pentafluorobenzyl)-N7-(2- [pentafluorobenzyloxy]ethyl)xanthine was subjected to HPLC, low-picogram amounts of the compound could be detected subsequently (off-line by gas chromatography electron-capture negative-ion mass spectrometry) after injection of pure mobile phase. This was in spite of significant, intermediate washing of the injector and column. It was determined that essentially 99.9% of this analyte contamination came from the injector. Use of two injectors is a practical remedy for this problem. PMID- 8450011 TI - Direct chiral separation of almokalant on Chiralcel OD and Chiralpak AD for liquid chromatographic assay of biological samples. AB - The four isomers of almokalant, a new antiarrhythmic substance under investigation, were separated by liquid chromatography on a Chiralcel OD and a Chiralpak AD column containing cellulose and amylose tris(3,5 dimethylphenylcarbamate), respectively. Both chiral stationary phases separate almokalant into the four isomers, but the retention orders are different if the carbamate is derivatized on cellulose or amylose. The Chiralcel OD column was used for the separation and determination of the isomers in urine at levels down to 100 nmol/l for the first three eluted and 200 nmol/l for the last with a relative standard deviation of less than 15%. The fluorescence response was increased by post-column ionization after stereoselective separation on the Chiralpak AD column. The isomers of almokalant could be determined at levels down to 10 nmol/l in plasma with a relative standard deviation of less than 15%. PMID- 8450012 TI - Determination of ephedrines in urine by high-performance liquid chromatography. AB - An improved high-performance liquid chromatographic method with ultraviolet detection for the simultaneous determination of norephedrine, norpseudoephedrine, ephedrine, pseudoephedrine, methylephedrine and ethylephedrine in urine is described. The six substances were separated on a reversed-phase column with phosphate buffer-triethylamine (pH 5.5) as the mobile phase. The linearity and reproducibility were satisfactory for the levels usually found in urine (1-30 micrograms/ml). PMID- 8450013 TI - Liquid chromatography-mass spectrometry for the determination of medetomidine and other anaesthetics in plasma. AB - A liquid chromatographic-atmospheric pressure chemical ionization mass spectrometric method is presented for the simultaneous determination of medetomidine and other anaesthetic drugs in solutions and dog plasma. The drugs examined were flumazenil, butorphanol, atropine, ketamine, xylazine, medetomidine, atipamezole and midazolam. The separation was carried out on a reversed-phase column using methanol-0.1 M ammonium acetate (3:2) as eluent. PMID- 8450014 TI - Reversed-phase high-performance liquid chromatography of the cardiac glycoside LNF-209 with refractive index detection. AB - LNF-209 is a glycoside, similar to digoxin, which has potential for use in the treatment of congestive heart failure. However, unlike digoxin it exhibits virtually no useful UV absorption spectra, making detection difficult. One means of detection is the refractive index detector, but like most bulk property detectors it has certain limitations. Its sensitivity is limited and it is sensitive to small changes in a number of parameters, such as temperature, mobile phase composition, and flow-rate. These parameters must be closely controlled to obtain a stable baseline. This paper describes the steps taken to control the system and the development and validation of an assay for LNF-209 in dosing solutions. The method developed is capable of quantitating LNF-209 in solutions of sterile water and 5% dextrose at concentrations ranging from 8 to 6000 micrograms/ml. The method is linear over this range and quantitative recovery is obtained. The overall average relative standard deviation for replicate analysis of several samples at various concentrations assayed over two days was 2.3%. PMID- 8450015 TI - Determination of oxiracetam in human plasma by reversed-phase high-performance liquid chromatography with fluorimetric detection. AB - Reversed-phase HPLC methodology utilizing pre-column derivatization and post column reaction fluorimetric detection has been developed and applied to the determination of oxiracetam in human plasma. The method involves preliminary isolation of oxiracetam and internal standard from plasma by solid-phase extraction prior to the formation of their n-propyl carbamate derivatives. The carbamate derivatives were subsequently isolated by solid-phase extraction and subjected to a gradient liquid chromatographic separation on an octadecylsilica column prior to on-line post-column alkaline hydrolysis to produce the corresponding primary amine, which was in turn derivatized with o-phthalaldehyde and 3-mercaptopropionic acid to yield a fluorescent isoindole. The isoindole was then quantified using a fluorescence detector. The method provided an on-column detection limit of 0.5 ng of oxiracetam and was sufficiently sensitive, accurate, and precise to support pre-clinical or clinical pharmacokinetic studies. PMID- 8450016 TI - Column-switching high-performance liquid chromatographic method for the determination of SK&F 106203 in human plasma after fluorescence derivatization with 9-anthryldiazomethane. AB - A sensitive and selective high-performance liquid chromatographic method was developed for the determination of SK&F 106203 3-(2-carboxyethylthio)-3-[2-(8 phenyloctyl)phenyl]propanoic acid, a potent peptidoleukotriene end organ receptor antagonist, in human plasma. The method involves isolation of SK&F 106203 and the internal standard (SK&F 104736) from plasma samples by liquid-liquid extraction prior to derivatization with 9-anthryldiazomethane. The derivatized samples were first subjected to a solid-phase extraction procedure prior to injection onto a short silica column, which is part of a chromatographic system equipped with an automated column-switching device. Column switching was used to heart-cut the chromatographic zone containing the peaks of interest from this first column and transfer it to an analytical silica column for further chromatographic separation. The peaks were quantified with an in-line fluorometer by measuring the fluorescence emission intensity at 415 nm after excitation at 365 nm. An on column detection limit of 0.625 ng was achieved for SK&F 106203 by optimizing the derivatization and chromatography conditions. The limit of quantification for SK&F 106203, using 250 microliters of plasma, was 20 ng/ml. Linear response in SK&F 106203/internal standard peak-height ratios was observed for SK&F 106203 concentrations ranging from 10 to 5000 ng/ml of plasma. Precision and accuracy were within 5% across the calibration range. The assay was sufficiently sensitive, accurate, and precise to support pharmacokinetic studies in humans. PMID- 8450017 TI - Normal-phase high-performance liquid chromatographic determination of epristeride, a prostatic steroid 5 alpha-reductase enzyme inhibitor, in human plasma. AB - An highly sensitive and selective high-performance liquid chromatographic method was developed for the determination of epristeride [17 beta-(N-tert.-butyl carboxamido)-androst-3,5-diene-3-carboxylic acid, SK&F 105657], a potent inhibitor of the prostatic steroid 5 alpha-reductase enzyme, in human plasma samples. Epristeride is currently in development for the treatment of benign prostatic hyperplasia. The analytical method involves isolation of epristeride and the internal standard [17 beta-(N,N-diisopropyl carboxamido) estra-1,3,5 (10) triene-3-carboxylic acid, SK&F 105419] from plasma by solid-phase extraction prior to chromatographic separation on an aminopropyl silica column, using hexane methylene chloride-2-propanol-acetic acid as the mobile phase, with subsequent ultraviolet absorption detection. The absolute recovery of epristeride from plasma was 90.2 +/- 2.96. The limit of quantification for epristeride was 2.5 ng/ml. Linear response was observed for concentrations of epristeride ranging from 1 to 500 ng/ml plasma. The assay was sufficiently sensitive, accurate and precise to support pharmacokinetic studies in human subjects. PMID- 8450018 TI - Rapid, sensitive high-performance liquid chromatographic method for the quantification of promethazine in human serum with electrochemical detection. AB - A method of analysis has been developed to quantify promethazine in human serum with a sensitivity that was suitable for bioavailability studies following a 50.0 mg rectal dose. The limit of quantification from 1.0 ml of serum for promethazine using electrochemical detection was 0.200 ng/ml. At this concentration, the total coefficient of variation obtained from seven replicates over the course of three days of validation was 7.53%. The amount of serum required, the ease of sample preparation and the precision of the method at the limit of quantification demonstrated an improvement over previous assays. A validation study was completed that included an evaluation of recovery, ruggedness, linearity of response, accuracy, precision, sensitivity, stability and selectivity. The method was then used to determine promethazine serum levels in a 36-subject bioavailability study following a 50.0-mg suppository dose. PMID- 8450019 TI - High-performance liquid chromatography of human glycoprotein hormones. AB - The chromatographic behavior of the glycoprotein hormones from human pituitary glands and of placental origin [thyroid-stimulating hormone, luteinizing hormone and chorionic gonadotropin (CG)] was studied. It was shown that hydrophobic interaction chromatography on a microparticulate packing and anion-exchange HPLC can be applied for the purification of these hormones. Reversed-phase HPLC on wide-pore C4-bonded silica at neutral pH can be applied for the determination of the above hormones and for the isolation of pure CG and its subunits. PMID- 8450020 TI - Immunoaffinity chromatography of recombinant Amb a I in the presence of a denaturing agent. AB - Recombinant proteins expressed in E. coli are often sequestered into inclusion bodies and require the use of denaturing agents in order to solubilize them. The recombinant form of Amb a I, the major allergen from short ragweed pollen, is one such protein. In some cases solubility can be maintained after the removal of the denaturing agent, particularly if the protein can be folded into its native conformation. However, not all proteins refold readily and after the removal of the denaturing agent the proteins will reaggregate and/or precipitate. In the case of Amb a I, the recombinant protein stays in solution at low concentrations but aggregates with itself and other proteins. The recombinant Amb a I is not expressed at high levels and may be toxic to E. coli. Therefore, isolation from a complex mixture of E. coli proteins was necessary. Monoclonal antibodies which recognize the denatured form of Amb a I were available, allowing for immunoaffinity purification. However, because the protein was not monomeric, this chromatographic technique did not provide an improvement in the purity level when run in normal buffer solutions. Analysis of one monoclonal antibody's stability to urea indicated it could tolerate the presence of 2 M urea and recover full activity. Use of this antibody as an immunoaffinity reagent in a column run in 2 M urea, which minimized aggregation of the E. coli produced proteins, gave a high degree of purification of recombinant Amb a I in one step. This illustrates the potential for the use of denaturing and other solubilizing agents in immunoaffinity chromatography of recombinant proteins. PMID- 8450021 TI - Separation of interleukins by a preparative chromatofocusing-like method. AB - A chromatofocusing-like method used in the large-scale separation of deamidated from amidated recombinant human interleukin-1 alpha (amino acids 117-271), derived from Escherichia coli, is described. Two major protein species having isoelectric points (pI) of approximately 5.3 and 5.1 were separated by high performance liquid chromatography using a sulfopropyl strong cation-exchange column. Unlike standard chromatofocusing technique, this method does not use carrier ampholytes during gradient separation of proteins, nor does it employ increased ionic strength for protein elution, the usual method for performing standard ion-exchange chromatography. N-Terminal sequence analysis of the protein with a pI of 5.3 revealed an Asn residue at position 32 as predicted by the cDNA sequence. The pI 5.1 species showed an Asp residue at the same position as a result of deamidation of Asn. This method was also used in the large-scale separation of N-Met from des-Met recombinant human interleukin-1 beta. PMID- 8450022 TI - Kinetic analysis of biotinylation of specific residues of peptides by high performance liquid chromatography. AB - A procedure employing C18 reversed-phase high-performance liquid chromatography (HPLC) is described for evaluating the kinetics of biotinylation of specific residues of peptides after reaction with N-hydroxysuccinimide esters of biotin. Utilizing this HPLC method, we determined the observed pseudo-first-order reaction rate constant (k'1) of biotinylation of lysyl residues in two model peptides, [biotinyl-Ser108]ProA-egg laying hormone (108-121) and pGlu-Lys-Trp-Ala Pro, to be 1.22.10(-2)s-1 and 1.08.10(-2)s-1, respectively, in 0.05 M sodium phosphate buffer, pH 8.2, at 25 degrees C. The respective reaction half-lives of the two peptides were 57 s and 64 s. In addition, HPLC analytical methods were established for determining the time-course of hydrolysis of biotinylating reagents at acidic and alkaline pH and for evaluating biotin reagent homogeneity. PMID- 8450023 TI - Accurate determination of log k'w in reversed-phase liquid chromatography. Implications for quantitative structure-retention relationships. AB - With increased understanding of the retention mechanisms of reversed-phase LC has come increased usage of the technique for the measurement of physico-chemical data, especially partitioning information that can be used for quantitative structure-activity relationships. However, the use of chromatographic retention requires that a standard set of mobile phase conditions be chosen. The choice of 100% water has theoretical advantages, as an aqueous phase-membrane phase is the most common system being modeled. However, experimental measurement of k' values with this mobile phase is difficult or impossible for most real solutes. Various retention extrapolation methods to 100% water have been proposed, but when compared, often yield different values for the same solute. Most of the extrapolation methods are based on the retention as a function of the mobile phase only. However, as the retention is controlled by solute partitioning between the mobile phase and stationary phase, stationary phase effects cannot be ignored. In this paper log k'w values extrapolated from different methods are compared to the measured values. Prediction of log k'w is attempted from the retention as a function of both the mobile phase and stationary phase. Solvatochromic analysis is used to deconvolute stationary and mobile phase effects. Log k'w values extrapolated from ET(30) plots are recommended as the most meaningful representation of retention for quantitative structure-retention relationships. PMID- 8450024 TI - Reversed-phase liquid chromatography with microspherical octadecyl-zirconia bonded stationary phases. AB - Microspherical zirconia particles were synthesized and surface modified with octadecylsilane compounds for reversed-phase high-performance liquid chromatography. Monomeric and "polymeric" octadecyl-zirconia bonded stationary phases were obtained by reacting the support with octadecyldimethylchlorosilane or octadecyltrichlorosilane, respectively. The surface coverage of the zirconia based stationary phases with octadecyl functions was approximately the same as that of octadecyl-silica sorbents. These phases were evaluated in terms of reversed-phase chromatographic properties with non-polar, slightly polar and ionic species over a wide range of mobile phase composition and pH. Monomeric octadecyl-zirconia with end-capping exhibited some metallic interactions with both basic and acidic solutes, but these interactions were greatly reduced in the presence of competing agents (e.g., tartrate ions) in the mobile phase. The "polymeric" octadecyl-zirconia sorbents exhibited higher retention than the monomeric ones with the various solutes investigated, and their residual absorptivities toward acidic solutes were much lower. The retention of non-polar and slightly polar aromatic compounds was quasi-homoenergetic on both types of octadecyl-zirconia stationary phases. Stability studies conducted at extreme pH conditions (pH 2.0 and pH 12.0), have shown that "polymeric" octadecyl-zirconia sorbents are more stable than their monomeric counterparts. These stationary phases were quite useful in the separation of polycyclic aromatic hydrocarbons, alkylbenzene and phenyl alkylalcohol homologous series, oligosaccharides, dansyl amino acids, peptides and proteins. PMID- 8450025 TI - Capillary zone electrophoresis and packed capillary column liquid chromatographic analysis of recombinant human interleukin-4. AB - Capillary zone electrophoresis (CZE) and packed capillary column liquid chromatography (micro-LC) have been applied to the analysis of the recombinant human protein interleukin-4 (rhIL-4). Separations for both the parent protein and its enzymatic digest were developed for the purpose of characterizing protein purity and identity. CZE separations of the intact protein were investigated over the pH range of 4.5 to 8.0 using uncoated fused silica capillaries. Gradient reversed-phase micro-LC was performed using 0.32 mm packed capillary columns at flow-rates of 5-6 microliters/min. Emphasis was placed on the ability of these methods to separate close structural variants and degradation products of the protein. Peptide mapping of the tryptic digest of rhIL-4 using a combination of CZE and micro-LC provided complimentary high resolution methods for establishing protein identity. Reproducible separations were achieved using sub-picomol amounts of sample. The advantages and problems encountered with these two techniques for characterizing rhIL-4 were assessed. PMID- 8450026 TI - Measurement of vitamin C by capillary electrophoresis in biological fluids and fruit beverages using a stereoisomer as an internal standard. AB - Ascorbic acid (or vitamin C) is an important component of many biological systems and various physiological roles have been described for it. A rapid and simple capillary electrophoresis method for ascorbic acid measurements in biological fluids as well as in beverages was developed. A stereoisomer of ascorbic acid, isoascorbic acid, not normally found in nature, was used as the internal standard for this assay. The analysis was performed in a 30 cm x 75 microns I.D. fused silica capillary with 100 mM tricine buffer, pH 8.8, and measured by UV absorbance at 254 nm. The method was sensitive to 1.6 micrograms/ml and linear to 480.1 micrograms/ml. Within-run R.S.D. was 3.2% (93.5 +/- 3.0 micrograms/ml, mean +/- S.D., n = 18) and run-to-run R.S.D. was 3.3% (35.6 +/- 1.2 micrograms/ml, mean +/- S.D., n = 10) and 1.9% (149.4 +/- 2.8 micrograms/ml, mean +/- S.D., n = 10). Average spiked recovery from human plasma samples was 98.0%. The technique has been demonstrated to be suitable for assay of vitamin C in biological samples and some fruit juices. PMID- 8450027 TI - Evaluation of several affinity chromatographic supports for the purification of maltose-binding protein from Escherichia coli. AB - To obtain affinity adsorbents with good mechanical resistance, suitable for the purification of maltose-binding protein (MBP) from Escherichia coli and genetically engineered proteins fused to MBP, a series of supports were prepared by grafting amylose on to agarose by different chemistries. Their capacities for MBP and their abilities to be used at relatively high flow-rates were examined. Efficient supports were most conveniently prepared by coupling amylose to epoxy activated agarose in an aqueous-organic mixture. PMID- 8450028 TI - Analysis of lysosomal degradation of fluorescein isothiocyanate- labelled proteins by Toyopearl HW-40 affinity chromatography. AB - Fluorescein isothiocyanate (FITC) was found to have a strong affinity to Toyopearl gel, which is used for gel filtration. FITC-labelled amino acids also showed affinity to Toyopearl gel, their elution from a Toyopearl HW-40 column being retarded. On the other hand, FITC-labelled proteins had no affinity to the gel and were recovered in the flow-through fractions. These findings were applied to the analysis of the degradation of various FITC-labelled proteins by lysosomal enzymes in vitro. FITC-labelled degradation products were easily separated from FITC-labelled substrate proteins on a small Toyopearl HW-40 column. Their production increased with the incubation time and was markedly suppressed by the proteinase inhibitor leupeptin. The FITC-labelled degradation product was identified to be mainly lysine with a FITC-labelled epsilon-amino group by its different elution position to those of lysine with a FITC-labelled alpha-amino group and other various FITC-labelled amino acids. PMID- 8450029 TI - Local expression of antiinflammatory cytokines in cancer. AB - To characterize the nature of the local cytokine response to cancer, we chose to investigate cytokine patterns in biopsy specimens of basal cell carcinoma (BCC). We hypothesized that a distinct pattern of local cytokine production may be characteristic of BCC, a neoplasia of epidermis, in comparison to the pattern of seborrheic keratosis (SK), a benign growth of epidermis. We analyzed cytokine mRNAs in BCC versus SK by performing polymerase chain reaction on mRNA derived from biopsy specimens. The mRNAs encoding cytokines for IL-4, IL-5, IL-10, and granulocyte macrophage colony-stimulating factor were strongly expressed in BCC lesions and weakly expressed in SK lesions. Conversely, IL-2, IFN-gamma, and lymphotoxin mRNAs were strongly expressed in SK lesions and weakly expressed in BCC lesions. The response to malignancy, BCC, was typified by cytokines characteristic of murine TH2 cells. This cytokine pattern favors humoral immunity with concomitant immunosuppression of cell-mediated immune responses. In comparison, the response to the benign growth, SK, was typified by cytokines characteristic of murine TH1 cells that favor cell-mediated immune reactions. The findings of a distinct cytokine pattern in skin cancer provide a framework to develop strategies for immunologic intervention. PMID- 8450030 TI - Lipoprotein-proteoglycan complexes induce continued cholesteryl ester accumulation in foam cells from rabbit atherosclerotic lesions. AB - We studied the metabolism of lipoprotein-proteoglycan complexes by macrophage derived foam cells. Foam cells were isolated from atherosclerotic rabbit aortas. ApoB-lipoprotein-proteoglycan complex was isolated from human aorta fibrous plaque lesions and LDL-proteoglycan complex was formed in vitro. Both in vitro and in vivo complexes stimulated cholesteryl ester synthesis in foam cells by a dose-dependent, saturable process that resulted in the intracellular accumulation of cholesteryl ester. Stimulation of cholesteryl ester synthesis was linear with time over a 32-h period. Polyinosinic acid inhibited the stimulation of cholesteryl ester synthesis by the complexes by 32-37%, whereas cytochalasin D only produced a 6-16% inhibition. Foam cells degraded 125I-LDL-proteoglycan complex and 125I-acetyl LDL in a saturable, dose-dependent manner. Excess unlabeled acetyl-LDL inhibited the degradation of 125I-LDL-proteoglycan complex by 52%, while LDL had no effect. Similarly, excess unlabeled complex suppressed the degradation of 125I-acetyl-LDL by 48%. Foam cells degraded 125I-methyl-LDL proteoglycan complex to the same extent as 125I-LDL-proteoglycan complex. These results show that foam cells from atherosclerotic lesions metabolize lipoprotein proteoglycan complexes predominantly via receptor-mediated endocytosis and consequently continue to accumulate intracellular cholesteryl ester. PMID- 8450031 TI - Transforming growth factor beta 2 in epithelial differentiation of developing teeth and odontogenic tumors. AB - Dysregulation of TGF beta 2, a modulator of cell growth and differentiation, can result in uncontrolled growth and tumor formation. Our comparative studies on the expression of TGF beta 2 mRNA and protein indicate that TGF beta 2 may primarily be a regulator of epithelial differentiation during tooth development (between 13 and 20 gestational wk) and tumorigenesis of odontogenic neoplasms. A paracrine mode of action for TGF beta 2 in early human tooth germ (cap/early bell stage) is suggested by location of mRNA in the mesenchyme surrounding the tooth germ, whereas protein is found in the epithelial dental lamina and enamel organ. During the late bell stage, TGF beta 2 gene expression shifted from the mesenchyme to the odontogenic epithelium and was colocalized with protein, suggesting an autocrine role for the terminal differentiation of ameloblasts. In odontogenic tumors of epithelial origin (ameloblastomas) and epithelial-ectomesencymal origin (ameloblastic fibromas), TGF beta 2 mRNA was mostly located in the mesenchymal tumor component and protein in the epithelial tumor component. Odontogenic ectomesenchymal tumors (myxomas) were not associated with TGF beta 2 mRNA and protein expression. The results imply that TGF beta 2 may play an important role in epithelial-mesenchymal interactions in human tooth morphogenesis and development of odontogenic tumors. PMID- 8450033 TI - Recombinant C1 inhibitor P5/P3 variants display resistance to catalytic inactivation by stimulated neutrophils. AB - Proteolytic inactivation of serine protease inhibitors (serpins) by neutrophil elastase (HNE) is presumed to contribute to the deregulation of plasma cascade systems in septic shock. Here, we report a supplementary approach to construct serpins, in our case C1 inhibitor, that are resistant to catalytic inactivation by HNE. Instead of shifting the specificity of alpha 1-antitrypsin towards the proteases of the contact activation and complement systems, we attempted to obtain a C1 inhibitor species which resists proteolytic inactivation by HNE. 12 recombinant C1 inhibitor variants were produced with mainly conservative substitutions at the cleavage sites for HNE, 440-Ile and/or 442-Val. Three variants significantly resisted proteolytic inactivation, both by purified HNE, as well as by activated neutrophils. The increase in functional half-life in the presence of FMLP-stimulated cells was found to be 18-fold for the 440-Leu/442-Ala variant. Inhibitory function of these variants was relatively unimpaired, as examined by the formation of stable complexes with C1s, beta-Factor XIIa, kallikrein, and plasmin, and as determined by kinetic analysis. The calculated association rate constants (k(on)) were reduced twofold at most for C1s, and appeared unaffected for beta-Factor XIIa. The effect on the k(on) with kallikrein was more pronounced, ranging from a significant ninefold reduction to an unmodified rate. The results show that the reactive centre loop of C1 inhibitor can be modified towards decreased sensitivity for nontarget proteases without loss of specificity for target proteases. We conclude that this approach extends the possibilities of applying recombinant serpin variants for therapeutic use in inflammatory diseases. PMID- 8450032 TI - Chylomicrons alter the fate of endotoxin, decreasing tumor necrosis factor release and preventing death. AB - The hypertriglyceridemia of infection was traditionally thought to represent the mobilization of substrate to fuel the body's response to the infectious challenge. However, we have previously shown that triglyceride-rich lipoproteins can protect against endotoxin-induced lethality. The current studies examine the mechanism by which this protection occurs. Rats infused with a lethal dose of endotoxin preincubated with chylomicrons had a reduced mortality compared with rats infused with endotoxin alone (15 vs. 76%, P < 0.001). Preincubation with chylomicrons increased the rate of clearance of endotoxin from plasma and doubled the amount of endotoxin cleared by the liver (30 +/- 1 vs. 14 +/- 2% of the total infused radiolabel, P < 0.001). In addition, autoradiographic studies showed that chylomicrons directed more of the endotoxin to hepatocytes and away from hepatic macrophages. Rats infused with endotoxin plus chylomicrons also showed reduced peak serum levels of tumor necrosis factor as compared with controls (14.2 +/- 3.3 vs. 44.9 +/- 9.5 ng/ml, mean +/- SEM, P = 0.014). In separate experiments, chylomicrons (1,000 mg triglyceride/kg) or saline were infused 10 min before the infusion of endotoxin. Chylomicron pretreatment resulted in a reduced mortality compared with rats infused with endotoxin alone (22 vs. 78%, P < 0.005). Therefore, chylomicrons can protect against endotoxin-induced lethality with and without preincubation with endotoxin. The mechanism by which chylomicrons protect against endotoxin appears to involve the shunting of endotoxin to hepatocytes and away from macrophages, thereby decreasing macrophage activation and the secretion of cytokines. PMID- 8450034 TI - Intrinsic radiation resistance of primary clonogenic blasts from children with newly diagnosed B-cell precursor acute lymphoblastic leukemia. AB - The radiation sensitivity of primary clonogenic blasts from 44 children with newly diagnosed B-cell precursor acute lymphoblastic leukemia (ALL) was analyzed using leukemic progenitor cell (LPC) colony assays. The derived values for SF2 (surviving fraction at 200 cGy) and alpha (initial slope of radiation survival curves constructed according to the linear quadratic model) indicated a marked interpatient heterogeneity in intrinsic radiation sensitivity of LPC populations. The SF2 values ranged from 0.01 to 1.00 (median = 0.430; mean +/- SE = 0.47 +/- 0.04), and the alpha values ranged from 0.000 to 3.272 Gy-1 (median = 0.280 Gy-1; mean +/- SE = 0.430 +/- 0.093 Gy-1). When CD19+ CD34+ versus CD19+ CD34- immunophenotypes were compared, a trend toward higher SF2 and lower alpha values were observed in LPC from CD34+ patients, consistent with greater radiation resistance. When patients were divided into three approximately equal groups based on increasing levels of CD34 expression, a clear ordering effect was observed indicating that increased CD34 expression levels are associated with significantly higher radiation resistance at the level of B-lineage LPC. The highest CD34 expression group (> or = 75% positivity) had 1.4-fold higher SF2 (P = 0.05) and twofold lower alpha values (P = 0.06) than the lowest group (< 30% positivity). Furthermore, the CD34 positivity of radiation resistant (alpha < or = 0.2 and SF2 > or = 0.5) B-cell precursor ALL cases was greater than the CD34 positivity of radiation sensitive (alpha > 0.2 and/or SF2 < 0.5) cases (56 +/- 9% versus 34 +/- 9%, P = 0.09). Whereas only 6 of 16 (38%) of radiation sensitive cases were CD34+, 11 of 15 (73%) of radiation resistant cases expressed CD34 (P = 0.04). Our results offer new insights into the inherent and/or acquired radiation resistance of primary clonogenic blasts from B-cell precursor ALL patients. PMID- 8450035 TI - Inhibition of a Plasmodium vinckei cysteine proteinase cures murine malaria. AB - Intraerythrocytic malaria parasites degrade hemoglobin as a principal source of amino acids for parasite protein synthesis. We have previously identified a Plasmodium falciparum trophozoite cysteine proteinase as a putative hemoglobinase and shown that specific inhibitors of this proteinase block the hydrolysis of globin and the development of cultured parasites. We now show that the murine malaria parasite Plasmodium vinckei has an analogous cysteine proteinase with similar biochemical properties to the P. falciparum proteinase, including an acid pH optimum, a preference for the peptide proteolytic substrate benzyloxycarbonyl (Z)-Phe-Arg-7-amino-4-methylcoumarin, and nonomolar inhibition by seven peptide fluoromethyl ketone proteinase inhibitors. Thus, P. vinckei offers a model system for the in vivo testing of the antimalarial properties of cysteine proteinase inhibitors. One of the proteinase inhibitors studied, morpholine urea (Mu)-Phe Homophenylalanine (HPhe)-CH2F strongly inhibited the P. vinckei cysteine proteinase in vitro and rapidly blocked parasite cysteine proteinase activity in vivo. When administered four times a day for 4 d to P. vinckei-infected mice, Mu Phe-HPhe-CH2F elicited long-term cures in 80% of the treated animals. These results show that peptide proteinase inhibitors can be effective antimalarial compounds in vivo and suggest that the P. falciparum cysteine proteinase is a promising target for chemotherapy. PMID- 8450036 TI - Metabolic handling of orally administered glucose in cirrhosis. AB - We used a dual-isotope method (oral [1-14C]glucose and intravenous [6-3H]glucose) to examine whether the oral glucose intolerance of cirrhosis is due to (a) a greater input of glucose into the systemic circulation (owing to a lower first pass hepatic uptake of ingested glucose, or to impaired inhibition of hepatic glucose output), (b) a lower rate of glucose removal, or (c) a combination of these mechanisms. Indirect calorimetry was used to measure oxidative and nonoxidative metabolism. Basal plasma glucose levels (cirrhotics, 5.6 +/- 0.4[SE], controls, 5.1 +/- 0.2 mmol/liter), and rates of glucose appearance (Ra) and disappearance (Rd) were similar in the two groups. After 75 g of oral glucose, plasma glucose levels were higher in cirrhotics than controls, the curves diverging for 80 min despite markedly higher insulin levels in cirrhotics. During the first 20 min, there was very little change in glucose Rd and the greater initial increase in plasma glucose in cirrhotics resulted from a higher Ra of ingested [1-14C]glucose into the systemic circulation, suggesting a reduced first-pass hepatic uptake of portal venous glucose. The continuing divergence of the plasma glucose curves was due to a lower glucose Rd between 30 and 80 min (cirrhotics 236 +/- 17 mg/kg in 50 min, controls 280 +/- 17 mg/kg in 50 min, P < 0.05, one-tailed test). Glucose metabolic clearance rate rose more slowly in cirrhotics and was significantly lower than in controls during the first 2 h after glucose ingestion (2.24 +/- 0.17 vs 3.30 +/- 0.23 ml/kg per min, P < 0.005), in keeping with their known insulin insensitivity. Despite the higher initial glucose Ra in cirrhotics, during the entire 4-h period the quantity of total glucose and of ingested glucose (cirrhotics 54 +/- 2 g [72% of oral load], controls 54 +/- 3 g) appearing in the systemic circulation were similar. Overall glucose Rd (cirrhotics 72.5 +/- 3.8 g/4 h, controls 77.2 +/- 2.2 g/4h) and percent suppression of hepatic glucose output over 4 h (cirrhotics, 53 +/- 10%, controls 49 +/- 8%) were also similar. After glucose ingestion much of the extra glucose utilized was oxidized to provide energy that in the basal state was derived from lipid fuels. Glucose oxidation after glucose ingestion was similar in both groups and accounted for approximately two-thirds of glucose Rd. The reduction in overall nonoxidative glucose disposal did not reach significance (21 +/- 5 vs. 29 +/- 3 g/4 h, 0.05 < P < 0.1). Although our data would be compatible with an impairment of tissue glycogen deposition after oral glucose, glucose storage as glycogen probably plays a small part part in overall glucose disposal. Our results suggest that the higher glucose levels seen in cirrhotics after oral glucose are due initially to an increase in the amount of ingested glucose appearing in the systemic circulation, and subsequently to an impairment in glucose uptake by tissues due to insulin insensitivity. Impaired suppression of hepatic glucose output does not contribute to oral glucose intolerance. PMID- 8450038 TI - Immune complexes from immunized mice and infected cystic fibrosis patients mediate murine and human T cell killing of hybridomas producing protective, opsonic antibody to Pseudomonas aeruginosa. AB - We examined the basis for the absence in cystic fibrosis (CF) patients of opsonic antibodies to the mucoid exopolysaccharide (MEP) antigen surrounding Pseudomonas aeruginosa that infect these patients. Opsonic antibodies to MEP are found in sera of the minority of CF patients that remain noncolonized into the second to fourth decades of life and protect rodents from chronic P. aeruginosa endobronchial infections. High titers of nonopsonic antibodies to MEP are found in P. aeruginosa-infected CF patients. Immunization of mice with doses of MEP that provoke only nonopsonic antibodies elicited CD3+, CD8+, T cell receptor alpha beta receptor+, major histocompatibility complex-unrestricted cytotoxic lymphocytes specific for hybridoma cells producing opsonic but not nonopsonic antibodies. Cytotoxicity was dependent on immune complexes on the surface of the T cells. Normal murine T cells could be activated by concanavalin A and sensitized with immune complexes for cytotoxic killing of hybridoma targets. CF patients infected with P. aeruginosa had serum immune complexes that sensitized concanavalin A-activated human T cells to kill murine hybridoma cells producing opsonic but not nonopsonic antibody. These results could explain the absence in infected CF patients of MEP-specific opsonins, an occurrence that accompanies the persistence of this infectious state. PMID- 8450037 TI - Chimerism and tolerance to host and donor in severe combined immunodeficiencies transplanted with fetal liver stem cells. AB - We have studied the peripheral T cell repertoire of two patients with severe combined immunodeficiency who were successfully treated with human histocompatibility leukocyte antigen (HLA)-mismatched fetal liver stem cell transplantation. The patients presented a split chimerism. T cells were of donor origin, whereas the B cells/monocytes were of the host phenotype. Interestingly, the natural killer (NK) cells in one patient were donor derived and in the other patient of host origin. The NK cells were functional but did not have antihost or donor reactivity. Despite the HLA mismatch between donor and host cells, complete tolerance was achieved in vivo, and a specific unresponsiveness of peripheral blood mononuclear cells from both patients toward the host cells was demonstrated in vitro. Nevertheless, we could isolate T cell receptor (TCR)alpha beta, CD4+ or CD8+, T cell clones specifically reacting with HLA class I and II molecules of the host. The CD4+ host-reactive T cell clones from both patients produced interleukins 2 and 5, interferon-gamma, granulocyte/macrophage colony-stimulating factor but are specifically defective in interleukin 4 production. The frequencies of CD8+ host-reactive T cells were high, and were in the same range as those observed for CD8+ alloreactive T cells. In contrast, no donor-reactive CD8+ T cells or host or donor-reactive TCR gamma delta + T cells were detected. These data indicate that, after fetal stem cell transplantation, donor-reactive, but not host-reactive cells, are deleted from the T cell repertoire. Therefore, a peripheral mechanism of suppression or clonal anergy, rather than clonal deletion, is involved in maintaining in vivo tolerance toward the host. PMID- 8450039 TI - Arylsulfatase B-deficient mucopolysaccharidosis in rats. AB - A rat colony with mucopolysaccharidosis VI was established and the clinical, pathological, and biochemical features were characterized. Affected rats had facial dysmorphia, dysostosis multiplex, and increased urinary excretion of glucosaminoglycans (GAGs). Ultrastructural studies revealed storage of GAGs throughout the reticuloendothelial cells, cartilage, and other connective tissues, but no deposition was observed in the nervous system. Biochemical analyses demonstrated that the excreted GAG was dermatan sulfate and the activity of hepatic arylsulfatase B was < 5% of the normal mean value. Pedigree analysis showed that the phenotype was inherited as an autosomal recessive single trait. The availability of a rat model of human mucopolysaccharidosis VI should permit the development and evaluation of various strategies to treat the human disease. PMID- 8450040 TI - Complete testicular feminization caused by an amino-terminal truncation of the androgen receptor with downstream initiation. AB - We have characterized the molecular defect causing androgen resistance in two 46,XY siblings with complete testicular feminization. Although binding studies in genital skin fibroblasts showed a reduced Bmax, an increased dissociation rate of ligand, and an 8S peak of dihydrotestosterone binding on sucrose density gradient centrifugation, no immunoreactive androgen receptor (AR) was detected in immunoblots using anti-NH2-terminal antibodies, suggesting an abnormal amino terminus. Sequence analysis of the AR gene revealed a point mutation CAG-->TAG (Gln-->Stop) at nucleotide 340. In vitro mutagenesis studies suggest the synthesis of the mutant AR is initiated downstream of the termination codon at reduced levels and that each molecule is functionally impaired. These results define a novel mechanism causing androgen resistance: the combination of decreased amount and functional impairment of AR caused by an abnormality within the amino terminus of the receptor. These findings suggest that domains important to the in vivo function of the receptor reside within the amino terminus and that disruption of these domains can occur with only subtle effects on receptor binding. Identification of this mutation made it possible to identify the mutant allele within the family and to ascertain antenatally that it was not present in a 46,XY fetal sibling of the proband at 9 wk gestation. PMID- 8450041 TI - Regulation of procollagen metabolism in the pressure-overloaded rat heart. AB - To determine the molecular events responsible for the disproportionate accumulation of myocardial fibrillar collagens during sustained hypertension, we examined the in vivo rate of procollagen synthesis, collagen accumulation, and intracellular procollagen degradation 1-16 wk after abdominal aortic banding in young rats. These measurements were correlated with tissue mRNA levels for type I and type III procollagen polypeptides. Banded animals developed moderate, sustained hypertension and mild left ventricular hypertrophy. Increased type III procollagen mRNA levels were detected early after banding and persisted for the entire observation period. Disproportionate collagen accumulation without histological evidence of fibrosis was noted within 1 wk after hypertension induction. Fibrillar collagen accumulation at this time point resulted not from a major increase in procollagen synthesis, but rather a marked decrease in the rate of intracellular procollagen degradation. Interstitial fibrosis, however, was observed 16 wk after banding. Type I procollagen mRNA levels were increased six fold, but only after 16 wk of hypertension. These results correlated well with the results of in vivo procollagen synthesis experiments at 16 wk, which demonstrated a threefold increase in left ventricular procollagen biosynthesis. We conclude that pretranslational as well as posttranslational mechanisms regulate fibrillar collagen deposition in the myocardial extracellular matrix during sustained hypertension. PMID- 8450042 TI - Related individuals with different androgen receptor gene deletions. AB - We have identified different members of one family affected by androgen insensitivity syndrome who have deletions of different exons of the X-linked androgen receptor (AR) gene. Two affected (XY) siblings have a deletion of exon E of the AR gene and their affected (XY) aunt has a normal exon E, but a deletion of exons F and G of the same gene. The mother and maternal grandmother of the children both carry the exon E deletion, but not the exon F, G deletion. Both deletions are 5 kb in length and have one breakpoint within a 200-bp region in intron 5; however, they extend in opposite directions. The probability that these two different deletions have arisen at random is extremely low, but the cause of this intriguing phenomenon remains to be found. PMID- 8450043 TI - An evaluation of several biochemical markers for bone formation and resorption in a protocol utilizing cyclical parathyroid hormone and calcitonin therapy for osteoporosis. AB - Female patients (n = 20) with osteoporosis, aged 66 +/- 5 yr were studied during a 24-h infusion of parathyroid hormone (PTH [1-34]) at a rate of 0.5 IU equivalents/kg.h, and then during a 28-d period of subcutaneous injections, at a dose of 800 IU equivalents per day. Thereafter half the patients received subcutaneous injections of calcitonin, 75 U/d for 42 d, and all patients were followed to the end of a 90-d cycle. Biochemical markers of bone formation (serum alkaline phosphatase, osteocalcin, and the carboxy-terminal extension peptide of pro-collagen 1) and bone resorption (fasting urine calcium, hydroxyproline, and deoxypyridinoline) were compared during treatment by the intravenous and subcutaneous route of PTH administration, and subsequently during calcitonin therapy. During intravenous PTH infusion there were significant reductions in all three bone formation markers, despite expected rises in urinary calcium and hydroxyproline. By contrast, the circulating markers of bone formation increased rapidly by > 100% of baseline values during daily PTH injections (P < 0.001). Significant increases in bone resorption markers were only seen at the end of the 28 d of injections, but were < 100% over baseline values, (P < 0.05). Quantitative bone histomorphometry from biopsies obtained after 28 d of PTH treatment confirmed that bone formation at both the cellular and tissue levels were two to five times higher than similar indices measured in a control group of biopsies from untreated osteoporotic women. Subsequent treatment of these patients with calcitonin showed no significant changes in the biochemical markers of bone formation and only a modest attenuation of bone resorption. Thus, PTH infusion may inhibit bone formation, as judged by circulating biochemical markers, whereas daily injections confirm the potent anabolic actions of the hormone. Sequential calcitonin therapy does not appear to act synergistically with PTH in cyclical therapeutic protocols. PMID- 8450044 TI - Two preproendothelin 1 mRNAs transcribed by alternative promoters. AB - Endothelin-1, initially identified as potent vasoconstrictor secreted by vascular endothelial cells, was subsequently found to have many effects on both vascular and nonvascular tissues. We have identified from a human placenta cDNA library a clone (cDNA-2) which corresponds to a novel 5'-extended preproendothelin 1 (preproET-1) mRNA. Comparison with the known preproET-1 mRNA (cDNA-1), showed that the two molecules share the same coding sequence but differ in the 5' untranslated region. Interestingly, cDNA-2 extends upstream of promoter regions previously shown to be essential for full preproET-1 expression. Primer extension and PCR analysis of human placenta RNA demonstrated the presence of additional transcription initiation sites located upstream of the previously identified preproET-1 CAP site. Moreover, the two mRNAs show different pattern of expression. To elucidate the mechanisms controlling the production of alternative transcripts we transfected COS-1 cells with a series of preproET-1 promoter deletion mutants. This analysis revealed that the human preproET-1 gene can be transcribed from a proximal and a distal promoter element which has hitherto been undetected. In addition, we demonstrate the presence of a region in the down epithelial specific expression. PMID- 8450045 TI - Role of pH in determining the cell-type-specific residual activity of glucocerebrosidase in type 1 Gaucher disease. AB - The properties of control and 370Asn-->Ser glucocerebrosidase, the frequently encountered mutated form of the enzyme in type 1 Gaucher disease, were studied in vitro as well as in situ. The catalytic properties of purified 370Asn-->Ser glucocerebrosidase were highly dependent on the assay conditions. The enzyme was deficient in activity towards substrate and in reactivity with the irreversible inhibitor conduritol B-epoxide (CBE) when activated by the bile salt taurocholate. In the presence of more physiological activators, the lysosomal activator protein saposin C and phosphatidylserine, the 370Asn-->Ser enzyme was near normal in kinetic properties at pH values approximately 5, but not at higher pH. In intact fibroblasts, the enzymic activity of the 370Asn-->Ser glucocerebrosidase and its reactivity with CBE were found to be clearly deficient. However, in intact lymphoblasts from the same patients, the behavior of the mutant enzyme was near normal. The catalytic efficiency of 370Asn-->Ser glucocerebrosidase in situ was also found to be highly pH dependent. When intact lymphoblasts were cultured in the presence of permeant weak bases, which increase the pH of acidic intracellular compartments, the catalytic efficiency of the mutant enzyme, as assessed by its reactivity with CBE, became markedly impaired. Our findings indicate that the intralysosomal pH in the intact cell can be expected to have a critical influence on the activation state of 370Asn-->Ser glucocerebrosidase and its ability to hydrolyse substrate. This phenomenon may partly underly the marked heterogeneity in clinical manifestation of Gaucher disease among patients with this mutated form of glucocerebrosidase. PMID- 8450046 TI - Mast cell activation enhances airway responsiveness to methacholine in the mouse. AB - Mast cell-deficient mutant mice and their normal littermates were used to determine whether activation of mast cells by anti-IgE enhances airway responsiveness to bronchoactive agonists in vivo. Pulmonary conductance was used as an index of airway response as the mice were challenged with increasing intravenous doses of methacholine (Mch) or 5-hydroxytryptamine (5-HT). Mast cell activation with anti-IgE enhanced pulmonary responsiveness to Mch in both types of normal mice (P < 0.0001 by analysis of variance) but not in either genotype of mast cell-deficient mouse. Additionally, anti-IgE pretreatment of genetically mast cell-deficient W/Wv mice whose mast cell deficiency had been repaired by infusion of freshly obtained bone marrow cells or bone marrow-derived cultured mast cells from congenic normal mice led to significant (P < 0.0001) enhancement of Mch responsiveness. 5-HT responsiveness was not significantly influenced by anti-IgE pretreatment in any of the mice studied. The data support the hypothesis that IgE-mediated activation of mast cells enhances pulmonary responsiveness to cholinergic stimulation. PMID- 8450047 TI - Analysis of T cell receptor variability in tumor-infiltrating lymphocytes from a human regressive melanoma. Evidence for in situ T cell clonal expansion. AB - Malignant melanomas are often infiltrated by T lymphocytes. It is postulated that the presence of tumor-infiltrating lymphocytes (TIL) reflects ongoing immune responses against transformed cells. Such "responses" appear generally inefficient with the potential exception of infrequent clinical situations characterized by spontaneous tumor regression. We have characterized here the molecular structure of the T cell receptor beta chain expressed by TILs in a case of regressive melanoma. Advantage was taken of the PCR technology to study T lymphocytes directly without cell culture. Experimentally validated V beta subfamily specific primers were used to evaluate the V beta usage in TILs and control samples. Our results reveal that clonal T cell populations, precisely defined by their V-D-J junctional sequences, are amplified at the tumor site. The existence of such local antigen-driven selections support the hypothesis that antitumor responses may indeed take place in regressive melanoma. PMID- 8450048 TI - Expression of int-2 oncogene in Kaposi's sarcoma lesions. AB - Fibroblast growth factors (FGFs), such as basic FGF, have been implicated in the growth of Kaposi's sarcoma (KS) cells in vitro. In the evaluation of the expression of the various genes of the different members of the FGF family and their receptors in fresh KS tissue specimens, int-2 was found to be expressed in more than half of the KS tumors examined. Using reverse transcription PCR, the expression of int-2 was detected in 21 of 38 (55.2%) fresh KS biopsy specimens. In contrast, int-2 mRNA transcripts were not found in normal appearing skin from the same patients except in one sample which was obtained from an AIDS patient with disseminated KS lesions. Sequence data confirmed that the amplified sequences were derived from int-2 mRNA with proper splicing. In addition, 12 nucleic acid alterations were identified in eight out of nine KS tumor samples sequenced. Using immunohistochemical methods, int-2 protein was detected in some of the spindle-shaped tumor cells surrounding the abnormal endothelial-lined vascular slits histologically characteristic of KS. Int-2 specific immunostaining was shown to be present in both the nuclei and cytoplasm of these spindle cells but was more pronounced in the nuclei. Neither amplification nor gross rearrangement of the int-2 gene was detected in KS lesions by Southern blot analysis. These results suggest that the expression of int-2 may play a role in the pathogenesis KS by stimulating local angiogenesis and cell proliferation. PMID- 8450049 TI - Mutations in core nucleotide sequence of hepatitis B virus correlate with fulminant and severe hepatitis. AB - Infection with hepatitis B virus leads to a wide spectrum of liver injury, including self-limited acute hepatitis, fulminant hepatitis, and chronic hepatitis with progression to cirrhosis or acute exacerbation to liver failure, as well as an asymptomatic chronic carrier state. Several studies have suggested that the hepatitis B core antigen could be an immunological target of cytotoxic T lymphocytes. To investigate the reason why the extreme immunological attack occurred in fulminant hepatitis and severe exacerbation patients, the entire precore and core region of hepatitis B virus DNA was sequenced in 24 subjects (5 fulminant, 10 severe fatal exacerbation, and 9 self-limited acute hepatitis patients). No significant change in the nucleotide sequence and deduced amino acid residue was noted in the nine self-limited acute hepatitis patients. In contrast, clustering changes in a small segment of 16 amino acids (codon 84-99 from the start of the core gene) in all seven adr subtype infected fulminant and severe exacerbation patients was found. A different segment with clustering substitutions (codon 48-60) was also found in seven of eight adw subtype infected fulminant and severe exacerbation patients. Of the 15 patients, 2 lacked precore stop mutation which was previously reported to be associated with fulminant hepatitis. These data suggest that these core regions with mutations may play an important role in the pathogenesis of hepatitis B viral disease, and such mutations are related to severe liver damage. PMID- 8450050 TI - Increased radiosensitivity of granulocyte macrophage colony-forming units and skin fibroblasts in human autosomal recessive severe combined immunodeficiency. AB - We studied the radiosensitivity of granulocyte macrophage colony-forming units (GM-CFU) in patients with a severe combined immunodeficiency (SCID). Three patients lacking both mature T and B cells showed a twofold higher GM-CFU radiosensitivity calculated as the DO value (dose required to reduce survival to 37%), and an identical observation was made with fibroblasts from one of these patients. A patient with an SCID with hypereosinophilia, i.e., Omenn's syndrome characterized by extremely restricted T cell heterogeneity and a lack of B cells, also showed abnormal GM-CFU radiosensitivity. In contrast, GM-CFU from a patient lacking only T cells (X-linked form of SCID) showed normal GM-CFU radiosensitivity. These data further support the similarity between human T(-) B( ) SCID and the murine acid mutation characterized by a defect in T cell receptor and immunoglobulin gene rearrangement, and by an abnormal double-strand DNA break repair function. In addition, they strongly suggest that the Omenn's immunodeficiency syndrome may be a leaky T(-)B(-) SCID phenotype as previously indicated by the coexistence of the two phenotypes in siblings. PMID- 8450051 TI - A new antiinflammatory compound, leumedin, inhibits modification of low density lipoprotein and the resulting monocyte transmigration into the subendothelial space of cocultures of human aortic wall cells. AB - Addition of leumedin, N-[9H-(2,7-dimethylfluorenyl-9-methoxy) carbon]-L-leucine at 30-60 microM together with LDL almost completely prevented the induction of monocyte chemotactic protein mRNA, reduced monocyte chemotactic protein 1 levels by 84%, and inhibited monocyte migration into the subendothelial space of cocultures of human aortic wall cells by < or = 98%. LDL incubated with leumedin formed a stable complex that remained intact even after refloating in an ultracentrifuge. Leumedin at 50 microM did not change conjugated diene formation during coculture modification of LDL or Cu++ catalyzed oxidation of LDL. Unlike LDL from control rabbits, LDL isolated from rabbits that were injected with 20 mg/kg leumedin was remarkably resistant to modification by the coculture and did not induce monocyte migration to a significant degree. Moreover, HDL isolated from rabbits injected with leumedin was far more effective in protecting against LDL modification by the artery wall cocultures than HDL from control rabbits. We conclude that leumedins can associate with lipoproteins in vivo, rendering LDL resistant to biological modification and markedly amplifying the protective capacity of HDL against in vitro LDL oxidation by artery wall cells. PMID- 8450052 TI - Osmolar regulation of endothelin-1 production by rat inner medullary collecting duct. AB - Recent evidence has implicated endothelin-1 (ET-1) as an autocrine inhibitor of inner medullary collecting duct (IMCD) sodium and water transport. The regulators of IMCD ET-1 production are, however, largely unknown. Because of the unique hypertonic environment of the IMCD, the effect of varying extracellular tonicity on IMCD ET-1 production was evaluated. Increasing media osmolality from 300 to 450 mosmol with NaCl or mannitol but not urea caused a marked dose- and time dependent reduction in ET-1 release by and ET-1 mRNA in cultured rat IMCD cells. In contrast, increasing osmolality had no effect on ET-1 production by rat endothelial or mesangial cells. To see if ET-1 varies in a similar manner in vivo, ET-1 production was assessed in volume expanded (lower medullary tonicity) or volume depleted (high medullary tonicity) rats. Urinary ET-1 excretion and inner medulla ET-1 mRNA were significantly reduced in volume depleted as compared to volume expanded animals. These results indicate that extracellular sodium concentration inhibits ET-1 production specifically in IMCD cells. We speculate that extracellular sodium concentration, via regulation of ET-1 production, provides a link between volume status and IMCD sodium and water reabsorption. PMID- 8450053 TI - Carnitine-acylcarnitine translocase deficiency with severe hypoglycemia and auriculo ventricular block. Translocase assay in permeabilized fibroblasts. AB - Deficiency of the enzymes of mitochondrial fatty acid oxidation and related carnitine dependent steps have been shown to be one of the causes of the fasting induced hypoketotic hypoglycemia. We describe here carnitine-acylcarnitine translocase deficiency in a neonate who died eight days after birth. The proband showed severe fasting-induced hypoketotic hypoglycemia, high plasma creatine kinase, heartbeat disorder, hypothermia, and hyperammonemia. The plasma-free carnitine on day three was only 3 microM, and 92% of the total carnitine (37 microM) was present as acylcarnitine. Treatments with intravenous glucose, carnitine, and medium-chain triglycerides had been tried without improvements. Measurements in fibroblasts confirmed deficient oxidation of palmitate and showed normal activities of the carnitine palmitoyltransferases I and II and of the three acyl-CoA dehydrogenases. A total deficiency of the carnitine-acyl-carnitine translocase was found in fibroblasts using the carnitine acetylation assay (1986. Biochem. J. 236:143-148). This assay has been further simplified by seeking conditions permitting application to permeabilized fibroblasts and lymphocytes. PMID- 8450054 TI - Transinhibition of C1 inhibitor synthesis in type I hereditary angioneurotic edema. AB - To ascertain the mechanism for decreased synthesis of C1 inhibitor (C1 INH) in certain patients with the autosomal dominant disorder hereditary angioneurotic edema, we studied expression of C1 INH in fibroblasts in which the mutant and wild type mRNA and protein could be distinguished because of deletion of exon 7 (delta Ex7). In the HANE delta Ex7 cells, the amount of wild type mRNA (2.1 kb) was expressed at 52 +/- 2% (n = 5) of normal, whereas the mutant mRNA was 17 +/- 1% (n = 5) of normal. Rates of synthesis of both wild type and mutant proteins (11 +/- 3 and 3 +/- 1% of normal, respectively) were lower than predicted from the mRNA levels. There was no evidence of increased C1 INH protein catabolism. These data indicate that there are multiple levels of control of C1 INH synthesis in type I hereditary angioneurotic edema. Pretranslational regulation results in < 50% of the mutant truncated 1.9-kb mRNA. In addition, translational regulation results in decreased synthesis of both wild type and mutatn C1 INH proteins. These data suggest a transinhibition of wild type C1 INH translation by mutant mRNA and/or protein. PMID- 8450055 TI - Transgenic models of hypertension: useful tools or unusual toys? PMID- 8450056 TI - Metabolism of triglyceride-rich lipoproteins during alimentary lipemia. AB - The metabolism of chylomicron remnants and VLDL was studied in healthy controls and normo- (NTG) and hypertriglyceridemic (HTG) patients with coronary artery disease after intake of an oral fat load. Specific determination of apo B-48 and B-100 enabled separation of the respective contribution of the two lipoprotein species. The postprandial plasma levels of small (Sf 20-60) and large (Sf 60-400) chylomicron remnants increased in controls and NTG patients. In contrast, only large chylomicron remnants increased in the HTG patients. An increase of large VLDL was seen in response to the oral fat load in all groups, whereas small VLDL were either unchanged in the controls and the NTG patients, or decreased in the HTG patient group. The whole plasma concentration of C apolipoproteins was essentially uninfluenced by the oral fat load, whereas the content in large triglyceride-rich lipoproteins paralleled the apo B elevations in controls and NTG patients. An even more prominent increase of apo B in large triglyceride-rich lipoproteins in the HTG group was not accompanied by an increase of C apolipoproteins. These findings indicate that chylomicrons compete with VLDL for removal of triglycerides by lipoprotein lipase and that the postprandial metabolism of triglyceride-rich lipoproteins is severely defective in hypertriglyceridemia. PMID- 8450057 TI - Changes in interleukin-2 and interleukin-4 production in asymptomatic, human immunodeficiency virus-seropositive individuals. AB - Infection with HIV results in an incremental loss of T helper cell (TH) function, which can occur years before CD4 cell numbers are critically reduced and AIDS is diagnosed. All TH function is not affected, however, because B cell activation and hypergammaglobulinema are also characteristic of this period. Recently, in a murine model of AIDS an early loss in production of the CD4 cytokines IL-2 and IFN-gamma was correlated with an increase in the B cell stimulatory cytokines IL 4, IL-5, and IL-10. We therefore assessed the production of IL-4 generated by PBL from HIV-seropositive (HIV+) individuals who did not have AIDS, yet who exhibited different TH functional categories based on their IL-2 production profiles. We observed that the decreases in recall antigen-stimulated IL-2 production were accompanied by an increase in IL-4 production. The loss of recall antigen stimulated responses in HIV+ individuals could be reversed in vitro by anti-IL-4 antibody. Our results suggest that the TH functions assessed by IL-4 production replace the normally dominant TH function of antigen-stimulated IL-2 production in the progression toward AIDS, and raise the possibility of cytokine cross regulation in AIDS therapy. PMID- 8450058 TI - Platelets and neutrophils are critical to the enhanced glomerular arachidonate metabolism in acute nephrotoxic nephritis in rats. AB - Nephrotoxic nephritis (NTN) is characterized by a marked increase in glomerular eicosanoid synthesis, which appears to play an important role in the pathophysiology of this disease model. In this study, we investigated the biochemical and cellular basis of this metabolic change. By examining the enzymatic conversion of exogenous substrates by intact glomeruli, we found that cyclooxygenase, TX synthase, and 5-lipoxygenase activities increased 4-, 8-, and 100-fold, respectively, in acute NTN. PGH2-PGE2 isomerase and leukotriene A4 hydrolase activities did not change. The cellular basis of these changes was examined using dissociated glomerular cells in vitro and by depleting platelets in vivo. Dissociated glomerular cells from nephritic glomeruli (largely mesangial cells and leukocytes) exhibited an enhanced arachidonate metabolism similar to intact nephritic glomeruli. Depletion of neutrophils (PMNs) from these cell preparations by 90% commensurately decreased 5-lipoxygenase and cyclooxygenase activity but had little effect on TX synthase activity. The recovered PMN fraction, however, did exhibit TX synthase activity. Immunocytochemical analysis of dissociated cells using an antiplatelet antibody demonstrated the presence of platelets, both adherent to cells and noncell associated. Depletion of platelets in vivo using this antibody substantially attenuated the increase in glomerular eicosanoid synthesis that accompanied NTN. Platelet depletion also decreased the influx of PMNs into the glomerulus by 50%. These data show that PMNs and platelets colocalize to the glomerulus in acute NTN and are coordinately essential to the increase in glomerular arachidonate metabolism. PMID- 8450059 TI - Beta cell mass and growth after syngeneic islet cell transplantation in normal and streptozocin diabetic C57BL/6 mice. AB - In islet transplantation, nonimmunological factors such as limited growth capacity or increased death rate could reduce the beta cell mass in the graft and lead to failure of the transplant. We studied the evolution of beta cell replication and mass after transplantation of insufficient, minimally sufficient, or excessive islet tissue. Streptozocin diabetic C57BL/6 mice received 150 or 300 syngeneic islets under the kidney capsule and normal mice received 300 islets. In streptozocin diabetic mice 300 islets restored normoglycemia; beta cell replication in transplanted islets was similar to replication in normal pancreas and beta cell mass in the graft remained constant. In contrast, 150 islets were insufficient to achieve normoglycemia; beta cell replication was increased initially but not by 18 or 30 d despite persistent hyperglycemia, and beta cell mass fell progressively. When islets were transplanted into normal recipients, beta cell replication remained normal but beta cells underwent atrophy and mass in the graft was substantially reduced. Therefore, with a successful islet transplant, in diabetic mice beta cell replication and mass remain constant. In contrast, when insufficient islet tissue is transplanted an initial increase in beta cell replication can not compensate for a decline in beta cell mass. When excessive islet tissue is transplanted, beta cell mass is reduced despite normal beta cell replication. PMID- 8450060 TI - Variable region expression in the antibody responses of infants vaccinated with Haemophilus influenzae type b polysaccharide-protein conjugates. Description of a new lambda light chain-associated idiotype and the relation between idiotype expression, avidity, and vaccine formulation. The Collaborative Vaccine Study Group. AB - Haemophilus influenzae b polysaccharide (Hib PS)-protein conjugate vaccines differ chemically and immunologically. To determine whether anti-Hib PS variable region expression might differ according to vaccine formulation, infants were vaccinated at 2, 4, and 6 mo of age with Hib PS coupled to either meningococcal outer membrane protein complex (Hib PS-OMPC) or tetanus toxoid (Hib PS-T), or Hib PS oligomers coupled to a mutant diphtheria toxin (Oligo-CRM). Two anti-Hib PS idiotypes were measured in sera obtained after the third injection: HibId-1, expressed by anti-Hib PS antibodies having the kappa II-A2 variable region, and HibId-2, a newly defined cross-reactive idiotype associated with a subset of anti Hib PS antibodies having lambda VII variable regions. HibId-1 was present in 33, 68, and 64% of infants given either Hib PS-OMPC, Oligo-CRM, or Hib PS-T, respectively (P < 0.001). The respective values for HibId-2 were 47, 18, and 10% (P = 0.001). Subjects who were vaccinated with Hib PS-OMPC or Hib PS-T and who produced detectable HibId-1-positive antibody, had significantly higher mean antibody avidity than subjects who did not produce HibId-1 positive antibodies. In contrast, Oligo-CRM evoked high avidity anti-Hib PS antibodies, irrespective of the idiotypic profile. These findings indicate fundamental differences in both variable region content and antibody quality elicited by different Hib PS conjugate vaccines. PMID- 8450061 TI - A role for glycosphingolipid accumulation in the renal hypertrophy of streptozotocin-induced diabetes mellitus. AB - Glucosylceramide (GlcCer) and related glycosphingolipids have been implicated as causal elements in both the growth of cells and in the regulation of hormonal signaling. We therefore studied whether the renal hypertrophy induced by diabetes was associated with enhanced synthesis of glycosphingolipids. 16 d after the induction of diabetes, increases in renal size and concentration of glucocerebroside and ganglioside GM3 were observed paralleling an increase in UDP Glc concentration. GlcCer synthase and beta-glucosidase-specific activities were no different between control and diabetic kidneys. The apparent Km of the GlcCer synthase with respect to UDP-Glc was 250 microM and was unchanged in the diabetic kidneys. The observed concentrations of UDP-Glc were 149 and 237 microM in control and diabetic kidneys, respectively. The UDP-Glc level is thus rate limiting with regard to GlcCer synthesis. To determine whether the changes in glycolipid content were functionally significant, diabetic and control groups were treated with the GlcCer synthase inhibitor, D-threo-1-phenyl-2-decanoyl amino-3-morpholino-1- propanol, 2 wk after the induction of diabetes. Kidney weights in the diabetic rats treated with D-threo-1-phenyl-2-decanoylamino-3 morpholino-1-propanol were no different than the control groups. Morphometric analysis of glomerular volumes paralleled changes in renal growth. Glycosphingolipid formation may therefore represent a significant pathway for glucose utilization in early diabetic nephropathy. PMID- 8450062 TI - Pathological and immunological effects of ingesting L-tryptophan and 1,1' ethylidenebis (L-tryptophan) in Lewis rats. AB - The eosinophilia-myalgia syndrome (EMS) has been associated with ingestion of L tryptophan (L-TRP) produced by a single manufacturer. Epidemiological data implicated 1,1'-ethylidenebis (L-tryptophan) (EBT) (peak 97 or peak E) as a possible etiologic agent. We showed previously that Lewis rats treated with the L TRP implicated in EMS develop fasciitis and perimyositis similar to those seen in human EMS. We now report the pathology associated with the treatment of Lewis rats with synthetic EBT and/or L-TRP. All animals treated for 6 wk with case associated L-TRP or EBT developed significant myofascial thickening, compared with animals in the vehicle control and control L-TRP groups. However, even those animals receiving the control L-TRP showed a mild but significant increase in the thickness of the myofascia, compared with vehicle-treated control animals. All animals except vehicle controls also exhibited significant pancreatic pathology, including fibrosis and acinar changes. Only animals treated with case-associated L-TRP for 6 wk showed evidence of immune activation with increased frequency of CD8, Ia, and IL-2 receptor-positive cells in the peripheral blood. Animals receiving L-TRP or EBT for < 6 wk did not show significant differences in myofascial thickness, although these animals did show pancreatic acinar changes. Although these results demonstrate for the first time the pathological effects of EBT, they do not rule out the possibility that other impurities in the EMS-case associated L-TRP may also contribute to some of the features of EMS. PMID- 8450063 TI - Hypoglycemia-associated autonomic failure in insulin-dependent diabetes mellitus. Recent antecedent hypoglycemia reduces autonomic responses to, symptoms of, and defense against subsequent hypoglycemia. AB - We hypothesize that in patients with insulin-dependent diabetes mellitus (IDDM), recent antecedent iatrogenic hypoglycemia is a major cause of hypoglycemia associated autonomic failure, a disorder distinct from classical diabetic autonomic neuropathy (CDAN), and that hypoglycemia-associated autonomic failure, by reducing both symptoms of and defense against developing hypoglycemia, results in recurrent iatrogenic hypoglycemia, thus creating a vicious cycle. We used the hyperinsulinemic (12.0 pmol.kg-1.min-1) stepped hypoglycemic clamp technique to assess autonomic and symptomatic responses to hypoglycemia and the insulin infusion test (4.0 pmol.kg-1.min-1) to assess defense against hypoglycemia on mornings before and after clamped afternoon hypoglycemia (approximately 2.8 mmol/liter) and hyperglycemia (approximately 11.1 mmol/liter) in patients with IDDM. Compared with nondiabetic subjects, IDDM with or without CDAN exhibited reduced epinephrine (P = 0.0222 and 0.0040) and pancreatic polypeptide (P = 0.0083 and 0.0056) responses to hypoglycemia. After afternoon hypoglycemia, lower plasma glucose concentrations were required to elicit autonomic and symptomatic responses during morning hypoglycemic clamps in patients without CDAN. At the 2.8 mmol/liter step, mean (+/- SE) epinephrine levels were 1,160 +/- 270 and 2,040 +/ 270 pmol/liter (P = 0.0060), pancreatic and total symptom scores were 22 +/- 3 and 41 +/- 7 (P = 0.0475) after afternoon hypoglycemia and hyperglycemia, respectively. During morning insulin infusion tests after afternoon hypoglycemia, nadir plasma glucose concentrations were 2.6 +/- 0.2 mmol/liter compared with 3.3 +/- 0.3 mmol/liter (P < 0.001) at the corresponding time points after afternoon hyperglycemia. Thus, we conclude: (a) elevated glycemic thresholds for autonomic responses to hypoglycemia are a feature of IDDM per se, not classical diabetic autonomic neuropathy; and (b) a single episode of afternoon hypoglycemia results in both elevated glycemic thresholds for autonomic and symptomatic responses to hypoglycemia and impaired physiological defense against hypoglycemia the next morning in IDDM. PMID- 8450064 TI - Lack of hormone binding in COS-7 cells expressing a mutated growth hormone receptor found in Laron dwarfism. AB - A single point mutation in the growth hormone (GH) receptor gene generating a Phe ->Ser substitution in the extracellular binding domain of the receptor has been identified in one family with Laron type dwarfism. The mutation was introduced by site-directed mutagenesis into cDNAs encoding the full-length rabbit GH receptor and the extracellular domain or binding protein (BP) of the human and rabbit GH receptor, and also in cDNAs encoding the full length and the extracellular domain of the related rabbit prolactin (PRL) receptor. All constructs were transiently expressed in COS-7 cells. Both wild type and mutant full-length rabbit GH and PRL receptors, as well as GH and prolactin BPs (wild type and mutant), were detected by Western blot in cell membranes and concentrated culture media, respectively. Immunofluorescence studies showed that wild type and mutant full-length GH receptors had the same cell surface and intracellular distribution and were expressed with comparable intensities. In contrast, all mutant forms (full-length receptors or BPs), completely lost their modify the synthesis ligand. These results clearly demonstrate that this point mutation (patients with Laron syndrome) does not modify the synthesis or the intracellular pathway of receptor proteins, but rather abolishes ability of the receptor or BP to bind GH and is thus responsible for the extreme GH resistance in these patients. PMID- 8450065 TI - Placental glucose transporter gene expression and metabolism in the rat. AB - In situ hybridization was used to evaluate patterns of gene expression for glucose transporters 1-4 (GT1-4) in the rat uteroplacenta from the time of implantation through term, and in vivo regional placental glucose metabolism was measured by 14C-labeled 2-deoxyglucose uptake. GT1 mRNA was highly abundant and GT3 was barely detected in the postimplantation decidual reaction. GT1 and 3 mRNAs were colocalized in the labyrinthine syncitiotrophoblast layer of the chorioallantoic placenta, which forms the membranous barrier between maternal and fetal circulations. The level of labyrinthine GT3 mRNA showed no change from midgestation through term; however, the volume of the labyrinth and hence total GT 3 gene expression increased greatly during this period. Labyrinthine GT1 mRNA levels, in contrast, showed significant diminution near term. GT1 mRNA was also localized in the placental growth plate, or junctional zone, where it was most abundant during the period of rapid placental growth and was decreased at term. Placental glucose metabolism, as reflected by steady-state 2-deoxyglucose uptake, was highest in the junctional zone during the rapid growth phase during midgestation, and decreased significantly at term, in parallel with GT1 gene expression. These findings suggest that GT1 is responsible for supplying glucose for use as a placental fuel and that GT3 is important for glucose transfer to the embryo. PMID- 8450066 TI - Modulation of monocyte activation in patients with rheumatoid arthritis by leukapheresis therapy. AB - One of the hallmarks in rheumatoid arthritis (RA) is the intense activation of the monocyte-macrophage system. In the present investigation, the modulation of blood monocyte activation was studied with regard to the secretion of cytokines and inflammatory mediators, and to the expression of cytokine receptors. Patients with severe active RA underwent repeated leukapheresis procedures that removed all circulating monocytes. Highly enriched monocyte preparations from the first and third leukapheresis were studied. There were striking differences between the two monocyte populations. Cells obtained from the first leukapheresis constitutively released large amounts of prostaglandin E2 (PGE2), neopterin, interleukin 1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha). In particular, IL-1 beta and neopterin production were further enhanced by stimulation with either interferon-gamma (IFN-gamma) or TNF-alpha without a synergistic effect. In contrast, cells derived from the third leukapheresis procedure showed a close to normal activation status with only low levels of cytokine and mediator production as well as a reduced response to cytokine stimulation. The number of the receptors for IFN-gamma and TNF-alpha was not changed between first and third leukapheresis. However, TNF-binding capacity was only detectable upon acid treatment of freshly isolated monocytes. A further upregulation was noted upon 24 h in vitro culture, suggesting occupation of membrane receptors and receptor down-regulation by endogenously produced TNF alpha. Northern blot analysis of cytokine gene expression was in good correlation with the amount of mediators determined on the protein level. These data indicate that cells of the monocyte-macrophage system are already highly activated in the peripheral blood in RA patients with active disease. These cells can be efficiently removed by repeated leukapheresis and are replenished by monocytes that have, with respect to cytokine and mediator production, a considerably lower activation status. PMID- 8450067 TI - Impaired degradation of leukotrienes in patients with peroxisome deficiency disorders. AB - The degradation of leukotrienes by beta-oxidation from the omega-end proceeds in peroxisomes (Jedlitschky et al. J. Biol. Chem. 1991. 266:24763-24772). Peroxisomal degradation of leukotrienes was studied in humans by analyses of endogenous leukotrienes in urines from eight patients with biochemically established peroxisome deficiency disorder and eight age- and sex-matched healthy infant controls. Leukotriene metabolites were separated by high-performance liquid chromatography, quantified by radioimmunoassays, and identified as well as quantified by gas chromatography-mass spectrometry. Urinary leukotriene E4 (LTE4) and N-acetyl-LTE4 excretions, relative to creatinine, were increased > 10-fold in the patients in comparison to healthy infants. The beta-oxidation product omega carboxy-tetranor-LTE3 averaged 0.05 mumol/mol creatinine in the controls but was not detectable in the patients. However, omega-carboxy-LTE4 (median 13.6 mumol/mol creatinine) was significantly increased in the patients' urine, whereas LTB4 (median 0.07 mumol/mol creatinine) and omega-carboxy-LTB4 were detected exclusively in the urines of the patients. These data indicate an impairment of the inactivation and degradation of both LTE4 and LTB4 in patients with peroxisomal deficiency. The increased levels of the biologically active, proinflammatory mediators LTE4 and LTB4 might be of pathophysiological significance in peroxisome deficiency disorders. This is the first and so far only condition with a pronounced urinary excretion of omega-carboxy-LTE4, omega carboxy-LTB4, and LTB4. This impaired catabolism of leukotrienes and the altered pattern of metabolites may be of diagnostic value. These findings underline the essential role of peroxisomes in the catabolism of leukotrienes in humans. PMID- 8450068 TI - Analysis of T cell responses in liver allograft recipients. Evidence for deletion of donor-specific cytotoxic T cells in the peripheral circulation. AB - Analysis of cell-mediated lympholysis in long-term liver allograft recipients indicated that there was a donor-specific unresponsiveness that could not be reversed by the addition of rIL-2 and/or mixed lymphocyte culture supernatant or by nonspecific stimulation of the cultures with PHA. Stimulation of recipient cells with semisyngeneic cells having both donor and third-party HLA antigens failed to reveal the presence of cytotoxic T cells (CTL) specific to the donor, whereas the CTL response to third-party antigens remained normal. Removal of B lymphocytes from the responding cell population did not influence the responses. Furthermore, limiting dilution analysis showed that the liver transplant recipients did not have detectable levels of CTL precursors (CTLp) reactive to the donor antigens, whereas their CTLp to third-party antigens remained normal. Donor-specific CTLp were present before and during the early post-transplant period; these cells were eliminated from the peripheral circulation by 10 mo after transplantation. Taken together, these results indicate that there is a deletion of CTLp specific to donor MHC antigens in the peripheral circulation of long-term liver allograft recipients that may account in part for the success of liver transplantation across MHC barriers. PMID- 8450069 TI - Analysis of segmental phosphate absorption in intact rats. A compartmental analysis approach. AB - Available information supports the dominance of the proximal intestine in inorganic phosphate (Pi) absorption. However, there is no strategy for analyzing segmental Pi absorption from a spontaneously propelled meal in an intact animal. We propose a solution using compartmental analysis. After intragastric administration of a 32P-labeled Pi liquid meal containing a nonabsorbable marker, [14C]polyethylene glycol (PEG), rats were killed at 2, 10, 20, 30, 60, 120, and 240 min. The gastrointestinal tract was removed and divided into seven segments, from which 32P and [14C]PEG were recovered. Data was expressed as a percentage of the dose fed, i.e., (32P[in segment] divided by 32P[fed]) and [14C]PEG[in segment] divided by [14C]PEG[fed]), respectively. A compartmental model was constructed and the rate constants for intersegmental transit and segmental absorption were estimated. The "goodness of fit" between the simulated model and the actual data indicates the estimated rate constants reflect in vivo events. The duodenum, with the highest transit and absorption rates, accounted for a third of the total absorption. However, the terminal ileum, with a lower absorption rate but a longer transit time, absorbed an equal amount of Pi. This approach allows the analysis of the mechanism and the regulation of Pi absorption under more authentic in vivo conditions. PMID- 8450070 TI - Cholesterol kinetics in subjects with bile fistula. Positive relationship between size of the bile acid precursor pool and bile acid synthetic rate. AB - Our aim was to identify and quantitate cholesterol pools and transport pathways in blood and liver. By studying bile fistula subjects, using several types of isotopic preparations, simultaneous labeling of separate cholesterol pools and sampling all components of blood and bile at frequent intervals, we developed a comprehensive multicompartmental model for cholesterol within the rapidly miscible pool. Data in six components (bile acids, esterified cholesterol in whole plasma, and free cholesterol in blood cells, bile, alpha lipoproteins, and beta lipoproteins) were modeled simultaneously with the SAAM program. The analysis revealed extensive exchange of free cholesterol between HDL and liver, blood cells, and other tissues. There was net free cholesterol transport from HDL to the liver in most subjects. The major organ that removed esterified cholesterol from blood was the liver. A large portion (4,211 mumol) of total hepatic cholesterol comprised a pool that turned over rapidly (t1/2 of 72 min) by exchanging mainly with plasma HDL and was the major source of bile acids and biliary cholesterol. Only 6% of hepatic newly synthesized cholesterol was used directly for bile acid synthesis: the analysis showed that 94% of newly synthesized cholesterol was partitioned into the large hepatic pool (putative plasma membrane free cholesterol) which exchanged rapidly with plasma lipoproteins. Bile acid synthetic rate correlated directly with the size of the large hepatic pool. In conclusion, hepatic and blood cholesterol pools and transports have been quantitated. HDL plays a central role in free cholesterol exchange/transport between all tissues and plasma. In humans, the metabolically active pool comprises a large portion of total hepatic cholesterol that, in part, regulates bile acid synthesis. PMID- 8450072 TI - Mandibular primary osteoplasty using orthotopic allografts. AB - This article is based on our results of 30-years experience in primary mandibular reconstruction using orthotopic allografts in 680 patients. Good and satisfactory outcome was achieved in 573 cases and unsatisfactory outcome in 62 (9.8%). Analysis of our clinical material shows that lyophilized and formalinized orthotopic allografts are an optimal material to correct mandibular defects of various size, sites and character. They facilitate formation of organotypical regenerated bone tissue in the place of the allograft and allow achievement of mandibular continuity and good functional and aesthetic results. PMID- 8450071 TI - Regulation of transferrin receptor expression and ferritin content in human mononuclear phagocytes. Coordinate upregulation by iron transferrin and downregulation by interferon gamma. AB - We have investigated the regulation of key human iron binding proteins in mononuclear phagocytes by IFN gamma and iron transferrin. In a previous study, we demonstrated that IFN gamma downregulates the expression on human monocytes of transferrin receptors, the major source of iron for the cell. In the present study, we show that IFN gamma also downregulates the intracellular concentration of ferritin, the major iron storage protein in the cell. By radioimmunoassay, the mean ferritin content of nonactivated monocytes was 361 +/- 107 fg/monocyte (mean +/- SEM) whereas the mean ferritin content of IFN gamma-activated monocytes was 64 +/- 13 fg/monocyte, an 82% reduction with activation (P < 0.01, t test). Consistent with its downregulating effect on these iron proteins, IFN gamma treatment also results in decreased iron incorporation. IFN gamma-activated monocytes incorporated 33% less iron from 59Fe-transferrin than nonactivated monocytes (P < 0.05, t test). Gel filtration chromatography revealed that incorporated iron is located primarily in ferritin in both nonactivated and IFN gamma-activated monocytes. Ferritin in IFN gamma-activated monocytes is saturated with approximately three times as much 59Fe as ferritin in nonactivated monocytes. We have also explored the effect of iron transferrin on transferrin receptor expression and intracellular ferritin content in human monocytes. We have found that iron transferrin markedly upregulates both transferrin receptor expression and intracellular ferritin content in both nonactivated (2.3- and 1.3 fold, respectively) and IFN gamma-activated (3.4- and 2.9-fold, respectively) monocytes. This study demonstrates that transferrin receptor expression and intracellular ferritin content in human monocytes is unidirectionally and coordinately upregulated by iron transferrin and unidirectionally and coordinately downregulated by IFN gamma. PMID- 8450073 TI - Facial palsy after sagittal split osteotomies. A survey of 1747 sagittal split osteotomies. AB - Facial nerve palsy following a sagittal split osteotomy is a rare but serious complication. The incidence of facial nerve injury in a group of 1747 patients who had undergone a bilateral sagittal split osteotomy (3494 sagittal splits) was determined and proved to be 0.26% (9 cases). The case histories of 2 patients are presented, and the etiology, diagnosis, treatment and prevention of this complication are discussed. PMID- 8450074 TI - Long-term osseous and soft tissue changes after large chin advancements. AB - When a large chin advancement is performed and a broad musculo-periosteal pedicle is preserved, excessive stretching of the suprahyoid musculature may occur, leading to instability or resorption of the advanced genial segment. The present study was designed to evaluate long-term osseous and soft tissue changes after large advancement genioplasties (greater than 10 mm), achieved by horizontal osteotomy of the inferior border of the mandible, with preservation of a musculo periosteal pedicle to the advanced genial segment. Bone remodeling and the inherent soft tissue changes were radiographically assessed in a long-term follow up period (mean = 26.8 months), with attention to observe progressive osseous changes. Despite the observed 17% bone resorption, the enveloping soft tissues of the chin followed the bony movement in a ratio of 1:0.83. Osseous resorption was not progressive, and the soft tissue changes remained unaltered. A broad musculo periosteal pedicle consistent with the surgical objective should remain attached to the advanced genial segment to minimize osseous resorption and achieve more predictable soft tissue changes. We emphasize the need for a longer follow-up period (25-30 years) to determine the effect of the stabilization devices and osseous remodeling, specially in younger patients. PMID- 8450075 TI - An orthodontic and cephalometric study on the results of the combined surgical orthodontic approach of the protruded premaxilla in bilateral clefts. AB - The anatomical aberration of the premaxilla in bilateral cleft lip and palate (BCLP) gives rise to many problems. Orthodontic and orthopaedic treatment alone often fail to correct this deformity. In this study, the results of a combined surgical-orthodontic approach were analysed. 22 BCLP-patients, who had undergone an osteotomy of the premaxilla in combination with secondary or tertiary bone grafting, were involved in this study. Two cephalograms were analysed from each patient, one prior to and one after osteotomy. Dental casts were made prior to orthodontic treatment, prior and after osteotomy of the premaxilla and after final orthodontic treatment. As a control group, BCLP-patients treated by the cleft palate centre, Oslo were used. Treatment planning of these two teams is comparable, except for the fact that in Oslo surgical repositioning of the premaxilla is never performed. Cephalometric values before and after osteotomy of the premaxilla were calculated. These values were corrected for growth by means of the Oslo-data. Differences before and after osteotomy were tested statistically with a paired t-test. After osteotomy, good arch form was achieved, the premaxilla was positioned more superiorly and normal inclination of incisors was achieved. It was not possible, however, to lower a high-positioned premaxilla to a normal vertical relationship. PMID- 8450076 TI - Early surgical-orthodontic treatment of mandibular hypoplasia in juvenile chronic arthritis. AB - This study is an intermediate evaluation of early surgical-orthodontic treatment in 7 patients with uni- or bilateral hypoplastic mandibular growth due to juvenile chronic arthritis. Resection of the condylar heads and reconstruction with costochondral grafts was undertaken between 10 and 14 years of age and followed by orthodontic treatment. At the latest follow-up, 2-4.5 years postoperatively, all patients showed mandibular growth. Some even showed a tendency towards progenia. The scheduling of the surgery in relation to completion of growth seemed to be of importance in relation to the magnitude of mandibular growth. At the latest check-up, only one patient had attained skeletal maturation and a more long-term follow-up is needed before this method can be finally evaluated. PMID- 8450077 TI - Thoracic complications of deeply situated serous neck infections. AB - Nine cases of complicated deep neck infections, occurring during a period of twelve years are presented. Complications observed were cervico-thoracic necrotizing fasciitis in 3 cases, purulent pleural effusion in 6 cases, pericardial effusion in 2, mediastinitis in 8 cases, jugular vein thrombosis and rupture of the innominate artery in one case each. Although 2 cases were managed initially with blind endotracheal intubation, all cases finally required tracheostomy. A cervico-mediastinal approach was useful for the early mediastinal involvement. Two patients died because of inadequacy of the multiple surgical procedures resulting in persistent infection and multi-organ failure and one because of uncontrollable bleeding after innominate artery rupture. PMID- 8450078 TI - Controlled bending of cranial bone grafts: a simple surgical technique. AB - The cranium serves as a primary bone graft donor site in reconstructive craniofacial surgery. However, the mechanical properties of cranial bone predispose to fragmentation when excessive bending forces are applied, or to a return to the original shape when bending forces are insufficient. The precise and sustained contouring of cranial bone therefore remains a practical clinical problem. This paper describes a simple surgical technique which relies upon the application of a miniplate to the cortical surface of the cranial bone segment prior to bending. The miniplate serves to reinforce the segment, allowing accurate shaping of cranial bone and maintenance of the newly acquired contour. PMID- 8450079 TI - In vitro determination of the forceps level for extraction of teeth for periodontal reasons. AB - The aim of the present study was to validate dentists' periodontal reasons for extraction by comparison with the in vitro periodontal status of extracted teeth. A national systematic random sample of Norwegian dentists (n = 500) was requested to record primary, secondary and tertiary reasons for tooth extraction for a period of 2 weeks in 1988. The response rate was 70%. The extracted permanent teeth from the first 2 patients of each dentist were collected. Of the 365 teeth, 329 satisfied the criteria for assessment of periodontal attachment after staining. Using a dissecting microscope (10x), 4 to 8 linear measurements were recorded per tooth. 159 of the 329 teeth had loss of periodontal support. Of the 93 teeth for which the dentists' reason for extraction included periodontal considerations, 1% had 1-10% loss of attachment, 59% had 11-50% loss and 40% had 51-76% loss of periodontal support. There was a significant correlation between in vitro measurements of attachment loss and a ranking of teeth on a scale from 1 to 3 based on the dentists' emphasis on periodontal reasons for extraction (The Spearman Rs = 0.29, p < 0.01). The results suggest that the forceps level for removal of teeth for periodontal reasons was set at a relatively early stage of the disease process by Norwegian dentists, and that there was a weak association between attachment loss and the dentists' emphasis on periodontal reasons for extraction. PMID- 8450080 TI - A longitudinal study on insulin-dependent diabetes mellitus and periodontal disease. AB - In the present two-year longitudinal investigation, the progression of periodontal disease was assessed after 1 year from the baseline examination in 38 dentate subjects and after 2 years in 22 dentate subjects with a mean duration of 18 years of insulin-dependent diabetes mellitus. The diabetics, aged 35 to 56 years at baseline, were under medical treatment at the outpatient clinic of the III Department of Medicine, University Central Hospital of Helsinki and at 2 diabetic clinics of the Helsinki Health Centre. Based upon their long-term medical records, 26 subjects were at baseline identified as having poorly controlled insulin-dependent diabetes (PIDD) with a mean blood glucose level of 12.5 mmol/l and a mean glycosylated hemoglobin (HBA1) level of 10.1%. 12 subjects were classified as having controlled insulin-dependent diabetes (CIDD) with a mean blood glucose level of 6.7 mmol/l and a mean HBA1 level of 9.2% at baseline. For each individual, recordings were made at baseline and after 1 and 2 years from the baseline for the plaque index, gingival index, pocket depth, loss of attachment, bleeding after probing, gingival recession, and radiographic loss of alveolar bone. At baseline and 2 years after the baseline examination, the PIDD subjects had similar plaque conditions as the CIDD subjects. At baseline and after 1 and 2 years from baseline the PIDD subjects had more gingivitis and bleeding after probing (P < 0.05, chi 2-test) than the CIDD subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450081 TI - Metronidazole in the treatment of localized juvenile periodontitis. AB - Systemic metronidazole and tetracycline were compared as adjunctive agents in the treatment of localized juvenile periodontitis (LJP). 27 patients with Actinobacillus actinomycetemcomitans-positive (Aa) LJP were treated with scaling and rootplaning, control of oral hygiene and periodontal surgery if indicated. The patients were randomly divided into 3 equal groups: the 1st group had metronidazole 200 mg x 3 x 10 days, the 2nd tetracycline 250 mg x 4 x 12 days, the 3rd group received no medication and served as a control. 6 patients had periodontal surgery. 4 sites with the most advanced bone loss as determined on radiographs were selected in each subject for test sites. Gingival index, gingival bleeding after probing (GB), probing depth (PD), suppuration, and radiographic bone loss were registered, and subgingival Aa was selectively cultured. GB and PD > or = 4 mm were registered in the whole dentition as well. All parameters were monitored at baseline and at 6 and 18 months after treatment. By the end of the study, Aa was suppressed to below detection level at all test sites only in the metronidazole group, at 17/26 sites (4 patients) in the tetracycline group and at 19/26 sites (6 patients) in the control group. Clinically, all groups showed improvement. In conclusion, metronidazole was more effective than tetracycline in the suppression of Aa and the suppression of Aa appeared to produce better clinical results. PMID- 8450082 TI - Comparison between mechanical cleaning and an antimicrobial rinse for the treatment and prevention of interdental gingivitis. AB - This study compared the efficacy of an antimicrobial mouthrinse (0.12% chlorhexidine gluconate) plus toothbrushing (mouthrinse group), mechanical interdental cleaning plus toothbrushing (mechanical group), and toothbrushing alone (control group), at reducing and preventing interdental gingival inflammation. 92 male subjects were examined for interdental inflammation using the Eastman interdental bleeding index at baseline, then monthly for 3 months after using one of the above oral hygiene regimens. The mechanical cleaning group had significant reductions in bleeding sites compared to baseline at 1 month (56.90% versus 13.17%) that persisted throughout the study (2 months = 6.65%, 3 months = 5.70%). The other regimens showed no significant bleeding reduction at any time point in the study. The mechanical interdental cleaning group showed improvement over baseline at 1 month with the full benefit apparent after 2 months. The effect of location in the mouth on bleeding reduction was also assessed. The % of posterior sites which bled was always higher than anterior sites. Analysis of maxillary versus mandibular, and buccal versus lingual sites showed no significant differences. Additional observations of the data demonstrated that sites which bled at baseline were more likely to stop bleeding in the mechanical cleaning group. Also, sites which did not bleed at baseline were unlikely to bleed subsequently when mechanical cleaning was used. Neither of these observations were true for the other cleaning regimens. These data show that only mechanical interdental plaque removal combined with toothbrushing is effective at reducing or preventing interdental inflammation. This underscores the importance of instituting mechanical interdental cleaning to eliminate interdental inflammation. PMID- 8450083 TI - Effects of a streptococcal lipoteichoic acid on complement activation in vitro. AB - This study describes activation of serum complement by lipoteichoic acid (LTA) from Streptococcus mutans OMZ 176, while in solution. Serum from 16 healthy students was taken. Test samples were incubated with increasing doses (1-5,000 micrograms/ml) of LTA or lipopolysaccharide (LPS) from Escherichia coli 0111:B4 for 1 h at 37 degrees C; then assayed for degradation of C3, C4 or factor B by crossed immunoelectrophoresis. Each preparation caused a significant (p < 0.05) dose-dependent conversion of C3. The response curves obtained were not statistically different. LPS was a stronger activator of the alternative pathway than LTA, as judged from analysis of C3 degradation in the presence of Mg2+/EGTA, and from their effects on factor B cleavage. LTA caused, however, pronounced alterations in the shape of C4 precipitation in the gels. Functional (hemolytic) assays showed that, when tested at 200 micrograms/ml, LTA and LPS triggered significant (p < 0.05) consumptions of both classical and alternative pathway proteins. LPS was a significantly (p < 0.05) stronger activator than LTA. Apparently, the C3 degradation found for this LTA involved the alternative pathway to a small extent; thus some other mechanism of fluid-phase C3 cleavage seemed also to be operative. PMID- 8450084 TI - Ultrastructure of plaque associated with polytetrafluoroethylene (PTFE) membranes used for guided tissue regeneration. AB - The purpose of the study was to examine the ultrastructure of plaque contaminating polytetrafluoroethylene (PTFE) membranes used for guided periodontal tissue regeneration. 8 patients treated with Gore-Tex membranes received daily antibiotics (650 mg x 2 Femepen) and rinsed with 10 ml 0.2% chlorhexidine during a healing period of 30 days. Following retrieval, the membranes were processed for electron microscopy. External aspects of 12 portions from 4 partially exposed membranes were selected for detailed ultrastructural examination. The plaque-membrane interface was characterized by the presence of fibrin or discontinuous accumulation of intermicrobial matrix. Adjacent plaque free areas of membrane surface exhibited no detectable electron-dense material. 3 structurally different groups of bacterial aggregations were observed on the strips: (i) dense layers of gram-positive cocci and rods dominated the external aspect of the open microstructure portion; (ii) cocci, rods and filamentous microorganisms embedded in fibrin filled the spaces of the open microstructure; (iii) a loosely arranged mixed microbiota consisting of gram-positive cocci and rods as well as of gram-negative microorganisms and spirochetes were present on the occlusive portion. Areas with morphologically intact bacteria alternated with areas with empty bacterial cell walls. One specimen also displayed degenerated Candida-like blastospores. This study shows that oral micro-organisms may colonize and extensively invade the open microstructure of PTFE material and that adhesion of plaque to the membrane surface is mediated either by fibrin or a discontinuous layer of intermicrobial matrix. PMID- 8450085 TI - Significance of some variables on interproximal alveolar bone height based on cross-sectional epidemiologic data. AB - The objective of the study was to analyze the significance of some variables on interproximal alveolar bone height, based on cross-sectional epidemiologic data from a Swedish survey conducted in 1983-1984, in the northern medical care district of Alvsborg county. 723 dentate individuals (92% of the randomly selected dentate individuals) with complete anamnestic, clinical and radiographic documentation were included in the statistical analyses. The computerized method used to measure interproximal alveolar bone height as a % of root length (B/R) provided data at each measurable interproximal surface of the individual teeth. On the population basis, a multivariate linear regression analysis showed that: (i) mean B/R values did not differ significantly between men and women, (ii) B/R value decreased with increasing age at a linear rate of 0.26% (0.04 mm) per year of age, (iii) the higher the calculus index value, the lower the mean B/R value, (iv) the higher the plaque index value, the higher the mean B/R value, (v) level of education, dentist attendance frequency and prevalence of defective margins of dental restorations did not show any statistically significant association with B/R, (vi) individuals attending the dental hygienist less than once every 2 years had higher mean B/R value than individuals attending the dental hygienist at least once every two years, and (vii) current smokers exhibited significantly lower mean B/R value than former and non-smokers. Individuals smoking more than 5 g of tobacco per day had lower mean B/R values than individuals smoking between 1 and 5 g of tobacco per day. There was no statistically significant relationship between snuffing and B/R. PMID- 8450086 TI - A 6-month home usage trial of a 1% chlorhexidine toothpaste (II). Effects on the oral microflora. AB - The effects of 1% chlorhexidine and 1% chlorhexidine/fluoride dentifrices on supragingival plaque flora were investigated in a 6-month home-usage study. 146 subjects were studied from whom plaque around 6 teeth was collected at baseline, 6 weeks and 24 weeks. Total anaerobic counts were reduced at 6 and 24 weeks in both active groups compared to control. No differences were seen in any other bacterial parameters. There was a significant decrease in the susceptibility to chlorhexidine of bacteria recovered from the subjects on the active treatments compared to control but, since the magnitude of effect was less than one dilution, this was not thought to be of any clinical significance. PMID- 8450087 TI - Changes of facial gingival dimensions in children. A 2-year longitudinal study. AB - Facial gingival surfaces of maxillary and mandibular anterior teeth were monitored to evaluate changes of the width of the keratinized and attached gingiva. 96 children 6 to 12 years of age were examined 2 x with an interval of 2 years. Measurements included dental plaque, gingival inflammation, probing depth, and width of keratinized and attached gingiva. In addition, study models were used to determine the facial/lingual position of the teeth. The results of this report, evaluating well-aligned teeth only, showed that during the 2-year observation period, increases in widths of the facial keratinized and attached gingiva took place. Increases occurred for the various teeth regions examined, and for deciduous as well as permanent teeth. During transition from the deciduous to the permanent dentition, patterns of change were variable. The increase of gingival widths was greatest for sites with the smallest baseline width of attached gingiva, and smallest for sites with the greatest baseline width. It was concluded that in well-aligned teeth, a conservative, monitoring approach prior to a corrective, surgical intervention seems prudent in children of this age with a minimal zone or absence of attached gingiva. PMID- 8450088 TI - Dimensional alterations of the gingiva related to changes of facial/lingual tooth position in permanent anterior teeth of children. A 2-year longitudinal study. AB - Maxillary and mandibular anterior permanent teeth in 38 children aged 7-12 years were examined 2 x with an interval of 2 years to determine whether spontaneous facial/lingual tooth position changes were related to alterations of the widths of keratinized and attached gingiva and the clinical crown height. Measurements included dental plaque, gingival inflammation, probing depth, and width of keratinized and attached gingiva. In addition, study casts from the baseline and 2-year examinations were used to measure clinical crown height and tooth position. The results showed that significant alterations in the widths of the keratinized and attached gingiva took place when the teeth changed positions in facial or lingual directions. The changes in gingival widths could to some extent be coupled to changes in clinical crown height. In teeth moving lingually, the gingival widths increased and the clinical crown height decreased. In teeth moving facially, the gingival widths decreased, and the facial gingiva sometimes receded. These gingival alterations call for examination of the facial gingiva as part of the monitoring of the development of the permanent dentition. PMID- 8450089 TI - Risk profile for Chlamydia infection in women from public health clinics in New York State. AB - The prevalence of chlamydial infection and associated risk factors were studied in 1531 women from ten clinics in New York State excluding New York City. Overall Chlamydia infection rates were 13.6%; 17.6% in eight high risk family planning and STD clinics, and 5.7% in two low risk college and private clinics. Risk factors for Chlamydia infection included: age < 20 years (odds ratio 1.6), use of oral contraceptives (odds ratio 2.0), a history of having more than one sexual partner (odds ratio 1.7) and, in one clinic where data was available, inflammation on Papanicolaou smears (odds ratio 2.1). These data helped secure funding for Chlamydia preventive services and permitted development of a risk profile (score card) of Chlamydia for each age group. Use of such a score card can be most helpful in assigning which patients could benefit most from Chlamydia cultures, especially in those areas where testing is unavailable or too costly to screen all patients. PMID- 8450090 TI - Perceived needs and unmet needs for formal services among people with HIV disease. AB - This study presents estimates of the prevalence of perceived needs and unmet needs among people with HIV disease in the United States for six areas of community services: mental health, drug treatment, home care, housing, transportation, and entitlements. The prevalence of service needs and unmet needs within racial, gender, drug use history, and other subgroups was also examined. The study is based on a nonrandom cross-sectional sample of 907 people with HIV disease interviewed between November 1988 and May 1989 in nine major urban areas of the United States. Respondents reported high levels of need and unmet need across a variety of service areas. One third or more of all respondents reported a need for mental health services (57%), housing (39%), entitlements (34%), and transportation (32%). Within each of the six service areas, 40% or more reported unmet need. Women, people of color, and injected drug users were more likely to report unmet service need in a number of areas. Given the limitations of the sampling and the focus on current needs, these estimates may represent a lower bound on the magnitude of service need and unmet need within this population. PMID- 8450091 TI - Medicine on British television: a content analysis. AB - Fifty-four British television programs on medical topics were viewed and analyzed during a four-month period in the winter of 1988-89. Medical programs of a nonfictional, nondramatic variety were represented on all four channels of British television with 75% appearing on the BBC. The primary format was that of a documentary; most offerings were during peak television viewing hours and were 30-50 minutes in length. Principal settings were within the realm of clinical medicine or health care delivery. The location of filming was in hospitals rather than outpatient areas. Doctors were presented as experts, but general practitioners were infrequently represented. The health care team was generally treated in a sympathetic manner. Psychiatric/behavioral and neurologic topics appeared frequently, with common medical problems and preventive medicine rarely emphasized. PMID- 8450092 TI - Towards a new system of health: the challenge of Western disease. AB - Over the last three decades, the concept of Western disease has become well established. Medicine has approached this group of diseases by searching for new cures but has achieved relatively little success. We argue that medicine should now accept the failure of this strategy and place a major emphasis on prevention. The key objective is to change the climate of opinion so that prevention is taken seriously by the general population. The chief activity should be a wide ranging public education campaign so as to persuade people to live a healthier lifestyle. Medicine will require restructuring in order to carry out this work. Medical education needs to be reformed so that medical students receive the necessary training. This must be done as part of an integrated approach in which government, industry and medical research all play a major role. Governments should use taxation and subsidies in areas such as food and tobacco so as to shift consumption patterns towards healthier products. Governments must also tighten laws on tobacco sales and advertising, support health education, and improve food labelling. Industry must be made far more responsive to the health needs of the population. This should be done both by public education, so as to alter demand, and by government action. Medical research should change its emphasis from studying the detailed mechanisms of disease ("complex research") to studying the role of lifestyle factors ("simple research"). PMID- 8450093 TI - A study of patient satisfaction with primary health care services in Saudi Arabia. AB - Patient satisfaction is of value to primary health care providers. The main objective of this study was to estimate patient satisfaction with respect to primary health care services in Riyadh City, Saudi Arabia. Fourteen primary health care centers were chosen randomly to represent various geographic areas of Riyadh. Information was collected through a pre-tested questionnaire used by thirty well-trained final year medical students. Systematic sampling of family files was conducted and the household head was interviewed. Nine hundred respondents were interviewed concerning their satisfaction with the services delivered. The findings were as follows: 40% were dissatisfied. One third of the dissatisfied expressed the view that the center was too far; 19.4% complained that the working hours of the center were not suitable; 38.9% complained of the absence of specialty clinics; 19.4% had language barriers with the physicians; 63.9% complained about delays at the center; 16.7% of the satisfied and 38.9% of the dissatisfied complained that the physicians did not satisfactorily explain their health problems and treatments. In 22.7% of the dissatisfied category, physicians' explanations were neither clear nor understandable. Among the satisfied, 74.6% said that primary health care center was the first choice if they felt sick; 61.1% of the non-satisfied category gave this response. The implications of these findings are discussed, and recommendations are given to rectify certain problems. PMID- 8450094 TI - Overweight among Mexican Americans and its relationship to life style behavioral risk factors. AB - The hypothesis positing differences between Mexican Americans and whites regarding attitudes and behaviors concerning obesity and other health issues was tested. A random sample of 1171 whites and 155 Mexican Americans aged 18 to 65 was selected. Two analyses were carried out. First, overweight Mexican Americans were compared with overweight whites. Second, overweight individuals were compared with normal weight counterparts within each ethnic group. Differences between overweight Mexican Americans and overweight whites disappeared after adjusting for the effects of sex, income, educational status, and marital status. Among whites, several factors remained significantly different when comparing overweight with normal weight individuals. Among Mexican Americans, however, all but one of the significant differences between overweight and normal weight individuals disappeared after adjusting for other variables. The implications of these results as they relate to the implementation of public health programs to deal with the prevention and treatment of obesity among Mexican Americans are discussed. PMID- 8450095 TI - African-American adolescents' knowledge, health-related attitudes, sexual behavior, and contraceptive decisions: implications for the prevention of adolescent HIV infection. AB - African-American adolescents (N = 195) completed measures of knowledge related to acquired immunodeficiency syndrome (AIDS), attitudes toward condoms, health locus of control, vulnerability to human immunodeficiency virus (HIV) infection, peer sexual norms, personal sexual behavior for the past 6 months, and contraceptive preferences. Hotelling's T2 tests revealed that girls were more knowledgeable about AIDS, reported fewer sexual partners, held more positive attitudes toward precautionary sexual behavior, and perceived themselves to have greater self control than boys. Five variables accounted for 44% of the variance in condom use: condom use from the 1st intercourse occasion, earlier grade in school, lower belief in an external locus of control, and higher scores on the Effect on Sexual Experience and Self-Control subscales of the Condom Attitude Scale. Implications for the content, format, and timing of HIV prevention with African-American adolescents are discussed. PMID- 8450096 TI - Effects of social support and relapse prevention training as adjuncts to a televised smoking-cessation intervention. AB - Smokers registering for a televised cessation program who also expressed interest in joining a support group and who had a nonsmoking buddy were randomly assigned to 3 conditions: no-contact control, discussion, and social support. All Ss received a self-help manual and were encouraged to watch the daily TV program. Ss in the discussion and social support conditions were scheduled to attend 3 group meetings (one with a buddy). Social support Ss and buddies received training in support and relapse prevention. A 4th analysis group was composed of Ss who failed to attend any of the scheduled meetings (no shows). There were strong group effects at the end of treatment. Abstinence rates were highest in the social support group, followed, in order, by the discussion group, no shows, and no-contact controls. The social support group improved outcome by increasing both the level of support and program material use (reading the manual and watching TV). PMID- 8450097 TI - Social problem solving in suicidal adolescents. AB - Whether adolescent suicide attempters would have deficits in interpersonal problem solving and the relation between social problem solving, suicide intent, and medical lethality were evaluated. Compared with psychiatric and normal controls, adolescents who attempted suicide exhibited poorer social problem solving abilities, particularly in terms of problem orientation. Specifically, suicide attempters brought more maladaptive cognitive-emotional-behavioral response sets to problematic situations than did psychiatric and normal controls. Both suicide attempters and psychiatric controls had similar deficits in problem solving skills (e.g., generation of alternatives, decision making, and solution implementation) compared with nonhospitalized peers. Social problem solving was not found to be correlated with suicide lethality or intent. PMID- 8450098 TI - Exploring a psychotherapeutic change sequence: relating process to intersessional and posttreatment outcome. AB - Process was related to intermediate and posttreatment outcomes for 34 patients undergoing multimodal group therapy. Exploratory time series analysis suggested that process variable effects differed with the phase of the therapy. It appeared that an emotionally warm bond occurred between patient and therapist in the sessions prior to therapist-rated improvement. A patient rating of insight followed in subsequent sessions. A negative feedback loop between patient symptom levels and therapist negative patient-directed feelings was demonstrated. Patient dysphoria in later therapy sessions seemed to reflect an earlier therapeutic failure. Ego strength directly exerted its positive influence on outcome in later sessions. The relation between in-therapy process trends and overall outcome supported these findings. PMID- 8450099 TI - Cognitive-behavior therapy for late-life insomnia. AB - Twenty-four older adults with persistent psychophysiological insomnia were randomly assigned to an immediate or a delayed cognitive-behavioral intervention in a waiting-list control group design. Cognitive-behavior therapy consisted of an 8-week group intervention aimed at changing maladaptive sleep habits and altering dysfunctional beliefs and attitudes about sleeplessness. Treatment was effective in reducing sleep latency, wake after sleep onset, and early morning awakening, and in increasing sleep efficiency. The magnitude of changes obtained on polysomnographic measures was smaller but in the same direction as that obtained on daily sleep diaries. Sleep improvements obtained by the immediate treatment group were replicated with the delayed treatment condition. Therapeutic gains were well maintained at 3- and 12-month follow-ups. Clinical validation of outcome was obtained through collateral ratings from the patients and their significant others. The findings indicate that late-life insomnia can be effectively treated with nonpharmacological interventions. PMID- 8450100 TI - Depression, burnout, and perceptions of control in hospital nurses. AB - Depression, burnout, and perceived job control (PJC) were assessed in 162 nurses. Depression accounted for over 19% of the variance associated with emotional exhaustion--an index of burnout--and PJC accounted for another 6%. Factor analysis of the scales used to measure depression and burnout documented their discriminant validity. Perceptions of uncontrollability were significantly related to higher levels of depression and burnout. Structural equations modeling suggested that perceived uncontrollability is associated with burnout, which, in turn, is related to depressive affect. Against a criterion of actual job control, non-burned-out subjects overestimated their control, whereas burned-out subjects approached complete agreement with criterion. Despite evidence for a "depressive realism effect," greater perceptual accuracy was not attributable to depression among the more burned-out nurses. PMID- 8450101 TI - Preparation for undergoing an invasive medical procedure: interacting effects of information and coping style. AB - The present study investigated the interacting effects of an information-based preparation and dispositional desire for information among first-time cardiac catheterization patients. Seventy-two male and female Ss were randomly assigned to either a high- or low-information preparation condition. Dispositional desire for information was assessed with the Krantz Health Opinion Survey and the Miller Behavioral Styles Scale. Desire for information was not associated with a desire for control. When desire for information and preparatory information level were matched, there was less behavioral anxiety, more problem-focused coping, and less emotion-focused coping during catheterization. Coping disposition alone did not affect adjustment during catheterization. Information condition did affect adjustment, with high information resulting in more positive self-statements and less time to complete the procedure. PMID- 8450102 TI - Gender and conflict structure in marital interaction: a replication and extension. AB - Twenty-nine married couples engaged in 2 videotaped discussions: 1 in which the husband requested a change in the wife and 1 in which the wife requested a change in the husband. Conflict behavior was assessed by self-report and observer ratings. Neither conflict structure (who requested the change) nor gender was associated with the positivity or negativity of spouses' behavior. During discussions of husbands' issues, wives and husbands did not differ in demand/withdraw behavior, whereas when discussing wives' issues, wives were more demanding and husbands were more withdrawing. Husband-demand/wife-withdraw interaction predicted an increase in wives' satisfaction 1 year later, whereas wife-demand/husband-withdraw interaction predicted a decline in wives' satisfaction 1 year later. These results replicate and extend those of our earlier study (Christensen & Heavey, 1990). PMID- 8450103 TI - Influence of psychoactive substance use on the reliability of psychiatric diagnosis. AB - The interrater reliability of diagnoses made on the basis of a structured interview for psychiatric patients with and without psychoactive substance use disorders (PSUDs) was examined. Forty-seven pairs of ratings by 9 different clinical interviewers were used. Results supported 3 major findings: (a) The interrater reliability for non-PSUD psychiatric diagnoses is quite high when a subject has no diagnosable PSUD; it is lower, though still substantial, when a PSUD is present. (b) Interviewers are not aware of this and are just as certain of the accuracy of their diagnoses when a PSUD is present as when one is not. (c) Interrater reliability is moderate to substantial as to the judgment of whether, when a non-PSUD diagnosis is present, it is caused by the use of psychoactive substances. The implications of these findings for the appropriate selection of treatments for dually diagnosed patients are discussed. PMID- 8450104 TI - Psychiatric symptomatology in persons with organic solvent exposure. AB - This study investigated psychiatric symptomatology, self-concept, locus of control, and daily events in persons with a history of exposure to mixtures of organic solvents. Exposed subjects were more likely than controls to report depression, anxiety, fatigue, confusion, and somatic concerns, which in turn were associated with certain exposure-related variables (e.g., cacosmia). There were no differences between the groups in self-concept, locus of control, or ratings of daily hassles and uplifts. Exposed persons may be able to accurately identify what they perceive as changes that are due to the exposure (e.g., anxiety) without attributing these specific adverse outcomes to dispositional variables. PMID- 8450105 TI - America's angriest home videos: behavioral contingencies observed in home reenactments of marital conflict. AB - Sequential analysis was used to compare the conflictual marital interactions of physically aggressive (PA, n = 17), verbally aggressive (VA, n = 15), withdrawing (WI, n = 18), and nondistressed, low-conflict (ND, n = 15) couples to describe behavior patterns characteristic of couples who report different marital conflict styles. Videotapes of couples enacting typical conflicts in their own homes were coded with a system designed to capture the affective aspects of communication. PA couples were characterized by the reciprocity of hostile affect and by rigid, highly contingent behavior patterns that were both stronger and longer lasting than those of other conflictual, but nonviolent, couples. In a limited way, ND couples demonstrated some of the same negative behavior patterns as the conflictual couples, but they were able to exit these negative interaction cycles quickly, which underscores the importance of further research into the de escalation of conflict. PMID- 8450106 TI - Power and violence: the relation between communication patterns, power discrepancies, and domestic violence. AB - This study hypothesized that power discrepancies in the marital relationship, where the husband is subordinate, serve as risk factors for husband-to-wife violence. The construct of marital power was assessed from 3 power domains operationalized by discrepancies in economic status, decision-making power, communication patterns, and communication skill. Three groups of married couples (N = 95) were compared: domestically violent (DV), maritally distressed/nonviolent (DNV), and maritally happy/nonviolent (HNV). DV couples were more likely than the 2 nonviolent groups to engage in husband demand/wife withdraw interactions. Within the DV group, husbands who had less power were more physically abusive toward their wives. Thus, violence may be compensatory behavior to make up for husbands' lack of power in other arenas of marriage. Difficulties in assessing marital power and future direction for the study of power and violence are discussed. PMID- 8450107 TI - A comparison of the generalization of behavioral marital therapy and enhanced behavioral marital therapy. AB - This study examined the generalization of behavioral marital therapy (BMT) and enhanced behavioral marital therapy (EBMT), which added cognitive restructuring, affect exploration, and generalization training to BMT. Couples' communication and cognitions were assessed in the clinic and at home. Both BMT and EBMT were effective in decreasing negative communication behaviors and cognition across settings, but there was little evidence of differential generalization or change between the treatments. A series of regression equations showed no significant association between the extent of change in communication or cognitions and change in frequency of marital disagreements or marital satisfaction. It is concluded that BMT results in impressive generalization of communication and cognitive change, but it remains to be demonstrated that these changes are crucial to improvements in marital satisfaction. PMID- 8450108 TI - The roles of conflict engagement, escalation, and avoidance in marital interaction: a longitudinal view of five types of couples. AB - Seventy-three couples were studied at 2 time points 4 years apart. A typology of 5 groups of couples is proposed on the basis of observational data of Time 1 resolution of conflict, specific affects, and affect sequences. Over the 4 years, the groups of couples differed significantly in serious considerations of divorce and in the frequency of divorce. There were 3 groups of stable couples: validators, volatiles, and avoiders, who could be distinguished from each other on problem-solving behavior, specific affects, and persuasion attempts. There were 2 groups of unstable couples: hostile and hostile/detached, who could be distinguished from each other on problem-solving behavior and on specific negative and positive affects. A balance theory of marriage is proposed, which explores the idea that 3 distinct adaptations exist for having a stable marriage. PMID- 8450109 TI - Predicting couples' response to marital therapy: a comparison of short- and long term predictors. AB - This study identified predictors of couples' response to marital therapy at termination and 4 years posttreatment for 55 couples receiving either behavioral or insight-oriented marital therapy. Couples were more likely to remain maritally distressed at termination if either spouse reported high levels of negative marital affect or depressive symptomatology at intake. Couples were more likely to be divorced or maritally distressed 4 years after completing therapy if spouses' intake measures reflected high levels of negative marital affect, poor problem-solving skills, low psychological resilience, high levels of depression, low emotional responsiveness, or if neither spouse was employed at a semiskilled or higher level position. Termination measures of negative marital affect and poor communication skills also predicted couples' status at 4-year follow-up. Joint contingency tables relating predictors to outcome were constructed. PMID- 8450110 TI - Preventing marital distress through communication and conflict management training: a 4- and 5-year follow-up. AB - This article reports the 4- and 5-year follow-up results of evaluating the effects of a marital distress prevention program. The program, Prevention and Relationship Enhancement Program (PREP), is a 5-session program designed to teach couples effective communication and conflict management skills. At the 5-year follow-up, intervention, as compared with control, couples had higher levels of positive and lower levels of negative communication skills and lower levels of marital violence. Data are also presented on couples who declined the program. Issues are discussed concerning selection effects, change mechanisms, and future directions for prevention research. PMID- 8450111 TI - In-session change in emotionally focused therapy. AB - This article presents 3 different studies of in-session changes in emotionally focused couples therapy (EFT). Studies of in-session conflict events demonstrate both that couples' conflict interaction at the end of treatment is more affiliative and interdependent than at the beginning of treatment and that peak session conflict interaction is deeper in level of experience and more affiliative than the interaction in poor session conflict episodes. In addition, events beginning with intimate, affective self-disclosure by one partner were found to involve greater affiliation in spouses' responses to the self-disclosure than in a control event not involving self-disclosure. The possible change processes in EFT are discussed in light of these results. PMID- 8450112 TI - Research on couples and couple therapy: what do we know? Where are we going? AB - This article discusses the outcome and process research on couple therapy and integrates the articles special section "Couples and Couple Therapy" into the discussion. All tested couple treatments show statistically significant effects relative to control groups, but there are no reliable differences between different theoretical models. Moreover, all tested approaches leave substantial numbers of couples unimproved or at least still somewhat distressed. A discussion of the strengths and weaknesses of various designs concludes that within-model comparisons have been more productive in producing knowledge than between-model comparisons. Recommendations for future research include developing a technology that would make possible matching studies focusing on Aptitude x Treatment interactions. Also, there needs to be greater emphasis on basic research and prevention. PMID- 8450113 TI - Effects of AIDS-related bereavement and HIV-related illness on psychological distress among gay men: a 7-year longitudinal study, 1985-1991. AB - In this study we examined the influence of acquired immunodeficiency syndrome (AIDS)-related bereavement on psychological distress from 1985 through 1991. We predicted that this relation would be influenced by personal knowledge of human immunodeficiency virus (HIV) infection and symptoms consistent with HIV-related illness. Interview data collected each year on a cohort of 746 gay men included information on the deaths and illnesses of network members caused by AIDS, as well as on psychological distress, sedative use, HIV-related symptoms, and HIV infection status. Significant main effects of bereavement were found in each year after controlling for both losses occurring from 1 to 2 years previously and for AIDS and HIV health status. The intensity and duration of these bereavement effects diminished over time. Groups of men who were both bereaved and classified as having AIDS or were HIV positive reported the highest level of distress in every year compared with the 3 other groups. PMID- 8450114 TI - Solubility parameters, fractional polarities, and bond strengths of some intermediary resins used in dentin bonding. AB - An effective bonding of resin composites to dentin is generally preceded by a conditioning of the surface of the dentin. Previous studies have indicated that the intermediary or adhesive resin should have specific wetting characteristics matching those of the conditioned dentin, in order that optimum bonding can be ensured. The wetting characteristics may be expressed in terms of solubility parameter (delta) and polarity (p) of the resin. The aims of the present study were to determine these variables for a number of compounds used in adhesive resins and to investigate the effects of delta and p on the shear bond strength to dentin. Solubility parameters were obtained according to the method of Small. Fractional polarities were calculated on the basis of measurements of refractive index and dielectric constant of the resins. In the measurements of bond strength, Scotchprep, EDTA + Gluma, or Al2Ox3/glycine were used as dentin conditioners in combination with intermediary resins having various delta and p. For each conditioner, the shear bond strength (BS) could be "explained" by an exponential expression of the form BS = e(a + bx), where x = (delta + cp + d)2, and where a-d are constants depending on the conditioned dentin. It may be concluded that solubility parameter and polarity of the intermediary resins are important variables in the process of bonding to dentin. PMID- 8450115 TI - Effects of initial temperature and tempering medium on thermal tempering of dental porcelains. AB - The objective of this study was to test the hypothesis that quenching of porcelain in silicone oil rather than in compressed air will significantly increase the flexure strength by reducing the potential for crack formation during transient cooling. A secondary hypothesis to be tested is that the initial tempering temperature can be reduced significantly below the porcelain maturing temperature of 982 degrees C but well above Tg without a decrease in strength. Opaque-body porcelain disks, 16 mm in diameter and 2 mm in thickness, with a thermal contraction mismatch (delta alpha) of -1.5, 0, and +3.2 ppm/degrees C were tempered from initial temperatures of 650, 750, 850, and 982 degrees C in silicone oil with kinematic viscosities of 50, 1000, and 5000 centistokes. Porcelain disks were also subjected to three cooling procedures in air: slow cooling in a furnace (SC), free convective cooling in a laboratory bench (FC), and tempering (T) by blasting the surface of body porcelain with air. The crack size induced by a Vickers microhardness indenter was measured within one minute after crack development. For determination of the influence of initial cooling temperature on biaxial flexure strength, six body porcelain disks (delta alpha = 0) were tempered in air from initial temperatures of 650, 750, 850, and 982 degrees C. The mean crack size of specimens tempered in oil was significantly smaller (p < or = 0.001) than that of specimens that were slowly-cooled or fast cooled in air for all thermal contraction mismatch cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450117 TI - The short-term fluoride release of a hand-mixed vs. capsulated system of a restorative glass-ionomer cement. AB - The present study investigated whether variability in fluoride release was reduced by use of a capsulated system as compared with a hand-mixed system based on the same qualitative and quantitative glass-ionomer formulation. Five operators independently prepared five disks of each type of glass-ionomer restorative filling material. The amount of fluoride released in water by each specimen after 1, 2, 3, 7, and 14 days was determined. The variance and the mean value of the fluoride release at a given time were independent of the operator, regardless of the glass-ionomer system considered. However, the variance and the mean value of the fluoride release at a given time were considerably greater for the capsulated system than for the hand-mixed system. A regression analysis further showed that the cumulative amount of fluoride released, [F], as a function of the time t conformed to [F] = a[1 - exp (-bt)] + ct0.5 for each glass ionomer specimen, suggesting the simultaneous occurrence of two processes. Whereas the parameter b was the same for the hand-mixed and capsulated system and was independent of both a and c, the latter parameters were positively correlated. Moreover, the values for a and c were significantly greater for the capsulated system. On the basis of these results, it is concluded that the mixing process drastically influences the short-term as well as the long-term fluoride release. PMID- 8450116 TI - Flexural strength and fracture toughness of Dicor glass-ceramic after embedment modification. AB - Previous studies on the surface properties of Dicor castable glass-ceramic have shown the formation of a specific crystalline phase at the glass ceramic/embedment interface. If this phase is not removed by grinding, it leads to an undesirable strength decrease. The aims of this study were: (1) to determine the nature of this surface layer, (2) to promote the formation of a different crystalline phase at the surface with the intention of improving the properties of the glass-ceramic, by modification of the composition of the Dicor ceramming embedment, and (3) to evaluate the fracture toughness and flexural strength of Dicor glass-ceramic after embedment modification. Modifications were made to the embedment by incorporation of 2.5 wt% of lithium fluoride and ceramming at various temperatures. X-ray diffraction was used to determine the crystalline nature of the surface layer. Fracture toughness was investigated by the indentation technique. The maximum bi-axial stresses were calculated after the samples were fractured in water on a ball-on-ring fixture at 0.5 mm/min. With the recommended embedment and ceramming cycle, the crystalline phase constituting the ceram layer was a calcium magnesium silicate CaMg(SiO3)2 (diopside). The crystalline composition of the ceram layer was successfully modified by addition of 2.5 wt% lithium fluoride to the embedment. This promoted the crystallization of mica in the ceram layer and increased the fracture toughness of the glass ceramic when the ceramming temperature was 950 or 975 degrees C. The flexural strength was significantly increased when the ceramming temperature was 1000 degrees C. PMID- 8450118 TI - Segregation in precious-metal dental-casting alloys. AB - The aim of this study was to conduct a theoretical analysis of segregation in Au Ag-Cu and Ag-Pd-Au-Cu dental-casting alloys, and to confirm and extend the results experimentally. Both theoretical and experimental data showed greater segregation in the Ag-Pd-Au-Cu alloy than in the Au-Ag-Cu alloy. There was very little segregation of gold, zinc, and platinum, while between the dendrites copper increased and silver and palladium decreased. PMID- 8450119 TI - Amplitude and timing of EMG activity in the human masseter muscle during selected motor tasks. AB - Electromyographic (EMG) activity in the human masseter muscle was registered from six different sites, in the anterior, middle, and posterior regions of the superficial and deep layers of the muscle, during static clenching tasks (intercuspal and incisal), selected jaw movements (alternating protrusion/retrusion, right/left latero-deviation, and open/close excursions), and unilateral chewing on right and left sides. Peak-EMG amplitudes and the timing of the peaks were compared. Activity in the regions of the deep masseter was either higher (in mastication and intercuspal open/close excursions) or lower (incisal clenching) than the activities in the superficial masseter. Superficial and deep masseter also differed in their timing of peak EMG: During chewing, peak activity passed from superficial to deep in the balancing-side muscle, and from deep to superficial on the chewing side. During free latero-deviations, peak activity started in the deep masseter, when the jaw moved to the right side (i.e., the side of the muscle), and then passed to the superficial regions, after the jaw movement was reversed to the left side. In addition, within the deep masseter there existed clear anteroposterior differences in activation level (during incisal clenching and open/close excursions) and in timing (during latero deviation). Such a differentiation of activity was not found in the superficial masseter. PMID- 8450120 TI - Kinetic aspects of gingival and periodontal ligament fibroblast attachment to surface-conditioned dentin. AB - An in vitro model has been developed for measurement of initial attachment of 3H labeled human gingival fibroblasts (HGF) and periodontal ligament cells (HPDL cells) to sieved dentin powder. Reproducible attachment was obtained and was closely related to the number of plated cells, the amount of dentin powder, the temperature, and the time (from 0 to 6 h) of incubation. HGF and HPDL cells had a high affinity for untreated dentin. Heat-denatured BSA coating of the dentin fully inhibited cell attachment, while a fibronectin coating had no significant effect. A surface conditioning of the dentin grains by 3% citric acid or by 2.5% minocycline-HCl increased the initial attachment of HPDL cells significantly (p < 0.05). Minocycline-HCl was more efficient than citric acid in that respect. In addition, HGF attachment to untreated dentin was highly significantly improved (p < 0.005) by a pre-incubation of the cells with 50 micrograms/mL of minocycline, and there was also indication (p = 0.067) of improvement by the presence of minocycline in the attachment medium, with a maximum of efficacy at 110 micrograms/mL. These results suggest that minocycline-HCl directly influenced the attachment properties of fibroblastic cells and that citric acid and minocycline HCl could act by different mechanisms. HGF and HPDL cells originating from the same patient displayed no significant difference in their attachment to dentin in this model. PMID- 8450121 TI - Effect of sensory denervation on the response of rat molar pulp to exposure injury. AB - Sensory nerve fibers that contain calcitonin gene-related peptide (CGRP) have been shown previously to sprout into inflamed tissue surrounding sites of pulpal injury. The sprouting fibers contain increased CGRP immunoreactivity (IR), and neuropeptide levels increase in the surrounding pulp. We compared denervated and innervated first mandibular molars of rats to determine whether the absence of sensory nerve fibers affected tissue survival and healing after pulp exposure. Significant differences were seen between innervated and denervated teeth six days after occlusal exposure, with more extensive necrosis in the denervated teeth, and less survival of vascular pulp. When exposures were on the side of the crown, there was no significant difference between the innervated and denervated teeth. Both the innervated and denervated teeth had begun to make reparative dentin and osteodentin by six days after tooth injury. This study shows that teeth with sensory denervation had an accelerated loss of pulp tissue following occlusal exposure compared with innervated teeth with similar injury. PMID- 8450123 TI - A histological study of the exfoliation of human deciduous teeth. AB - For clarification of the histological details of the shedding of human deciduous teeth, exfoliated and extracted deciduous teeth were examined by light and electron microscopy. After the roots were completely resorbed, the dentogingival junction migrated along the inner resorbing surface and finally reached the pulpal surface of the crown. At the same time, the gingival epithelium also proliferated and migrated under the crown of the deciduous tooth in such a way that part of it lined the residue of the pulp and another part lined the surface overlying the erupting successional tooth. This phenomenon took place from various sides of the tooth surface. Therefore, just before exfoliation, the migrated gingival epithelium formed narrow necks of tissue, and the crown was only superficially attached to the gingiva by them. The final shedding of the tooth appeared to occur by a tearing of these narrow tissue regions. The results of the present study suggest that the dento-gingival junction as well as gingival epithelium play important roles in the process of exfoliation of human deciduous teeth. PMID- 8450122 TI - A microbiological study of primary root-caries lesions with different treatment needs. AB - Samples of altered or carious dentin for microbiological culture were obtained from 301 primary root-caries lesions in 59 patients by means of a standardized sampling procedure. This involved the cleansing of each root surface of extraneous supragingival plaque by means of a hand-held toothbrush and distilled water and the collection of the sample with a sterile dental excavator passed through the entire vertical dimension of each lesion. The total number of colony forming units (cfu) in each sample and the numbers of mutans streptococci (primarily Streptococcus mutans), lactobacilli, yeasts, and Gram-positive pleomorphic rods (GPPR) were determined. Individual bacterial counts were expressed as log10 (cfu per sample), as a percentage of the total number of bacteria per sample, and as a frequency of isolation from lesions with different clinical diagnostic criteria. Clinical measurements of each lesion were made for color, texture, position relative to the gingival margin, and treatment need. Lesions classified as soft yielded significantly more bacteria, mutans streptococci, lactobacilli, and GPPR than leathery lesions, which yielded more bacteria than hard lesions. Lesions were classified into 5 treatment categories: soft and restore, leathery and restore, leathery and debride of caries; leathery and treat therapeutically; and hard no treatment. The total numbers of bacteria, mutans streptococci, lactobacilli, GPPR, and yeasts decreased significantly with decreasing treatment need. The frequency of isolation of mutans streptococci, lactobacilli, and yeasts was significantly greater from lesions requiring restoration and from lesions situated within 1 mm of the gingival margin. We suggest that the majority of root caries is initiated adjacent to the gingival margin. PMID- 8450124 TI - Esthetic dentistry--a health service? PMID- 8450125 TI - Conference report: "Disorders of the Oral Mucosa." 43rd Annual Meeting of the Arbeitsgemeinschaft fur Kieferchirurgie within the German Dental Association (Deutsche Gesellschaft fur Zahn-, Mund- und Keiferheilkunde. PMID- 8450126 TI - Changing patterns of fluoride intake. PMID- 8450127 TI - Degrees in midwifery: aspirations and realities. PMID- 8450128 TI - Determinants of a health-promoting lifestyle: an integrative review. AB - This paper reports on an integrative review of the research literature published between 1983 and 1991 that focused on identifying the determinants of a health promoting lifestyle. Twenty-three studies were reviewed, six of which were concerned with children and adolescents and the remaining 17 with adults. A meta analysis of correlations for each study determinant was conducted using the Pandora System. Results indicated that self-efficacy was the strongest predictor of a health-promoting lifestyle, followed by social support, perceived benefits, self-concept, perceived barriers and health definition. The most frequently studied determinants were not the best predictors of a health-promoting lifestyle. PMID- 8450129 TI - An assessment of the value of health education in the prevention of childhood asthma. AB - A research project, which looks at the value of health education in the prevention of childhood asthma, is described. The project was a controlled trial by a health visitor focused within the community. This exploratory research looked at three groups of children over a 2-year period, and compared the effect of: (a) individual health education, and (b) group health education. During the first year, two groups were active, one receiving individual health education, the other collecting data of the same type. During the second year, a third group was involved in health education sessions. The findings have been similar in both cases, in that both groups have demonstrated a good improvement in knowledge of asthma and its treatment. Through the active involvement of using a peakflow meter and diary records in the health education programme, both groups receiving health education have shown a significant improvement in the morbidity indicators related to night symptoms and restricted activities. The qualitative analysis of the research also highlighted the value parents of asthmatic children place on counselling. PMID- 8450130 TI - Suggested community psychiatric nursing interventions with clients suffering from anorexia nervosa and bulimia nervosa. AB - Clients suffering from the fasting and gorging syndromes of anorexia and bulimia nervosa are at significant risk of self-harm even if treated with apparent success in hospital. Two major issues (not inevitably co-existing) appear to be at work in these illnesses; distorted perception by the sufferer of his or her own body appearance and stressful interpersonal relationships originating in one of a variety of groups of which the sufferer is a member. (Fear of psychosexual maturity, that is, the clients' inability to develop an age-appropriate sexual identity, is treated in this paper as being the product of faulty interactional patterns; it is also a less clear-cut issue in bulimia nervosa than in anorexia.) A supervised hospital in-patient treatment regime concentrating upon weight gain, effective discouragement of purgation and vomiting, possible drug treatment and perhaps dual or independent usage of individual or group psychotherapy with focused cognitive-behavioural task-oriented approaches, will not realize effective change unless these issues are resolved. Community psychiatric nurses (CPNs) are well-placed to observe and supervise people with eating disorders who are potentially vulnerable to relapse following discharge from hospital. Strategies for effective CPN interventions in the community care of anorectic and bulimic clients are suggested in the paper. PMID- 8450131 TI - Screening elderly people: a multidisciplinary concern. AB - The Elderly Screening Survey was carried out in 1990 as a follow-up to a similar study completed by the Centre for the Study of Primary Care in 1988. The aim of these two studies was to look at national differences in the types of screening programmes for elderly people and, specifically, to look at who carries out these programmes. The Elderly Screening Studies of 1988 and 1990 can be located within the ongoing debates about screening. In particular, given the implications of the general practitioner contract arrangements, these studies provide information on the discussion about the role and involvement of community nurses in screening older people. The results suggest that screening programmes for this age group had become more tailored to 'age-related need' in 1990 as compared to 1988. In 1990, districts were more likely to employ a wider variety of nursing personnel in carrying out screening schedules. Furthermore, it was evident that more districts were employing district nurses and practice nurses to implement screening assessments than in 1988. Attention is drawn to the lack of guidelines at district level on screening activities. The need to re-assess training provision particularly for practice nurses is highlighted. PMID- 8450132 TI - The significance of a sense of coherence for subjective health in persons with insulin-dependent diabetes. AB - The strength of an insulin-dependent, diabetic (IDDM) person's sense of coherence (SOC), conceptualized according to Antonovsky's salutogenetic model, was related to patterns of problem-solving and to emotional coping strategies. These personal SOC scores were also related to reported positive experiences, problems in daily life, problems in relation to the environment, worries about long-term complications, tedium and well-being which had been measured 5 years earlier. In the entire IDDM group the mean score for the SOC was 143. There was a significant correlation between the SOC scores and coping patterns (Z--2.053, P < 0.04). The subgroup labelled 'experts' had the highest SOC scores. There were also significant correlations between the SOC scores and problems in relation to the environment (r--0.08, P 0.03), tedium (r--0.69 P 0.01) and well-being (r--0.64, P 0.02). There were no correlations between the SOC scores and metabolic control, reported experiences that the disease had positively influenced the diabetic person's life, problems in daily life, or worries about long-term complications. It was concluded that a sense of coherence seems an important factor which contributes to successful emotional coping with the demands of the disease. As subjective health is an important nursing goal the salutogenic model appears to have potential utility in the care for the person with IDDM. PMID- 8450133 TI - Intuition as a function of the expert nurse: a critique of Benner's novice to expert model. AB - Benner's model of skill acquisition is currently receiving considerable interest from nurse educationalists, and promises to form the basis for some curricula offered by colleagues of nurse education. This paper debates the 'novice to expert' model and seeks to explain exactly what an 'expert' is. The Benner model proposes that one component of expertise is working from an intuitive base. This claim is disputed and the definition of intuition is contested. Alternative explanations to account for the intuitive responses of Benner's subjects are suggested. PMID- 8450134 TI - Primary nursing: autonomy or autocracy? AB - There has been an almost exponential increase in the number of clinical areas using primary nursing as a mode for delivering nursing care. Concurrently, the amount of written material pertaining to primary nursing has grown. In this paper, a small sample of this literature is reviewed. Most of the literature can be seen as either descriptive or as evaluative research. Many of the papers reviewed have methodological weaknesses; also the findings are equivocal about the advantages and the nature of primary nursing. A major problem appears to be that the basic tenets, beliefs and values of primary nursing have not been systematically investigated; thus attempts to evaluate primary nursing without such a philosophical analysis may be misdirected. This paper argues that such an analysis: (a) is now necessary; (b) requires a qualitative research approach to generate theory; and (c) that a grounded theory methodology is the most appropriate way to do this. A preliminary field study is briefly described and the generated data discussed. PMID- 8450135 TI - Measuring the impact of nursing interventions in the community: a selective review of the literature. AB - In a resource conscious environment, it is imperative that nurses use their skills and knowledge to provide an optimum service. It is suggested that nurses working in the community must measure the impact of their nursing interventions to guide their own role development and to inform the purchasing process. This literature review has revealed, however, that little progress has been made in this area by nurses within the community setting. Indeed, it is suggested that research is needed to test reliable and valid methods of outcome measurement. PMID- 8450136 TI - Exploring consumer views of care provided by the Macmillan nurse using the critical incident technique. AB - This study focuses on descriptive accounts of one Macmillan nurse's work, as provided by key individuals coming into contact with this specialist professional service. Twenty respondents (eight patients, five carers, five district nurses and two general practitioners) were interviewed using a variation of the critical incident technique. Data were analysed in terms of meaningful observed events (critical happenings) that were perceived as effective or ineffective with respect to the delivery of high-quality nursing care. Some variations were found between groups of respondents in their perception of the nurse's role. However, there was a general emphasis on the possession of specialist knowledge of terminal cancer care and the positive impact of interventions to both the patient and to lay and professional carers. The critical incident technique was found to be a valuable method for eliciting detailed accounts of the work of the nurse in this specialized field of practice. PMID- 8450137 TI - Feminist research: definitions, methodology, methods and evaluation. AB - The literature relating to feminist research both within and beyond nursing is reviewed in this paper. Feminist research is located within a post-positivist paradigm, and various definitions are considered. The distinctive methodological approach of feminist research is discussed, and interviewing and ethnography are evaluated as suitable methods for use in feminist research. Oakley's (1981) paper on interviewing women is subjected to criticism. A final section examines attempts by three sets of writers to propose evaluation criteria for feminist research. The review concludes that a number of paradoxes and dilemmas in feminist research have yet to be resolved. PMID- 8450138 TI - The nature of comfort to hospitalized medical surgical patients. AB - Historically, comfort has been a quintessential aspect of nursing practice. Currently, it is questionable whether or not comfort remains an integral facet of nursing care. The increasing trend to focus on the technological and institutional aspects of patient care rather than the individual's response to illness and subsequent treatment is heard again and again from the growing vocal consumer movement. This study of comfort from a patient's viewpoint (a grounded theory) attempted to address both the current state of comfort care found within nursing practice and the patient's view of what constituted comfort while in hospital. The most significant finding was that comfort was not a passive process whereby the patients waited in hope of receiving comfort (i.e. such as someone to come and soothe their fevered brows). Comfort was found to be a dynamic process, with each patient actively engaged in increasing personal comfort levels. Indeed, the lack of comfort was found to be the stimulus for patients to embark on a process called 'integrative balancing'. PMID- 8450139 TI - The impact of the first child on marital happiness. AB - The effects of the first child on parent's marital happiness were studied using a sample of 185 subjects. Marital happiness scores were found to be lower in the subjects who were pregnant, those with 5-month-old children, and those with 24 month old children than the childless couples. This study suggests trends indicating that first children may influence marital happiness in a negative manner. These findings will assist nurses in the preparation of families for childbearing and the potential changes that may result. PMID- 8450140 TI - Nurses' experiences of caring for ethnic-minority clients. AB - This paper describes a research study designed to explore the experiences of nurses caring for ethnic-minority clients and to identify any specific problems nurses encounter when caring for these clients. Data were collected through a process of in-depth interviews with 18 trained nurses. The findings of the study suggest that nurses caring for ethnic-minority clients share many common experiences, problems and challenges. Difficulties in communication with clients and a lack of knowledge about cultural differences were highlighted by all respondents. The lack of holistic care and the inability to develop a therapeutic relationship were identified as major areas of frustration and stress. The study demonstrates that there is an urgent need to develop cultural knowledge in nurse education programmes and that nurses need help and support with communication difficulties. Interpreting services and dietary facilities available for ethnic minority clients were also found to be inadequate and it is suggested that there is a need to review these facilities within hospitals. PMID- 8450141 TI - Evaluation of the pain response by Mexican American and Anglo American women and their nurses. AB - This study examined the relationship between ethnicity and pain. The study addressed three major research questions. The first question asked whether there was a significant difference in Mexican American women's and Anglo American women's response to cholecystectomy pain. Secondly, the nurses' attribution of pain to each of the two ethnic groups was compared. Finally, the patient's evaluation of the pain being experienced was compared to the nurse's evaluation of the pain the patient was experiencing. The sample consisted of 60 patient subjects and 60 nurse responses. Data were collected at two major teaching hospitals in southern California. Patient pain was measured using the McGill Pain Questionnaire, amount of analgesics and three physiological measures. The nurse's assessment of patient pain was measured using the Present Pain Intensity scale. MANOVA was used to analyse differences between the two ethnic groups on all measures of pain and no significant differences were found between the two ethnic groups on any of the measures of pain. However, nurses judged the two ethnic groups' pain response differently, assigning more pain to Anglo Americans. Finally, a dependent t-test was used to compare nurses' and patients' evaluation of pain. There were significant differences. Nurses evaluated the patients' pain as being less than patients did. Pearson product-moment correlations were used to examine the relationship between pain and sample characteristics of both patients and nurses. For the nurses, pain was significantly related to the patient's education, place of birth, language and religion. PMID- 8450142 TI - Clinical role activities of nurse teachers in Project 2000 programmes. AB - This paper presents the findings related to the clinical role activities of nurse teachers in Project 2000 programmes. Data were collected by a Delphi survey of 25 colleges of nursing that had implemented Project 2000 between September 1989 and April 1991. The findings from the Delphi survey were explored more fully through in-depth interviews with a sample of the respondents. The findings identified a very strong commitment of the respondents to a clinical liaison role. But they did not perceive their role to be one of teaching students through 'hands on care'; they felt this was the role of the qualified staff in the clinical areas. The respondents considered it important to maintain their clinical credibility through theoretical updating rather than being able to perform as an expert practitioner. PMID- 8450143 TI - The use of curriculum objectives in nursing education. AB - This empirical study has its roots in the Finnish nursing education reform of the 1980s. The reform emphasized the formulation of national curriculum objectives and a criterion-oriented, responsive evaluation of learning outcomes. The data were collected by using a questionnaire, answered by Finnish graduating nursing students in 1990 (n = 379). The results indicate certain problems in the criterion-oriented evaluation. PMID- 8450144 TI - Nursing education in the private sector. AB - With perhaps some minor variations, it can be claimed that colleges/schools of nursing have viewed their raison d'etre as providing education for pre registration students of nursing. The particular philosophy of the college would determine whether or not in-service education and post basic courses figured highly as educational priorities. Whether pre- or post-registration, colleges have been their remit almost entirely within statutory frameworks. With the advent of Project 2000 many schools/colleges amalgamated in order to provide multiple branches of nurse education. However, anticipated numbers of entrants to nursing have not always materialized and we are now led to believe that revised staffing ratios will result in decreasing numbers of qualified nursing staff. Faced with decreased numbers of recruits to nursing, colleges of nursing can undergo even larger amalgamations or look elsewhere for some of their business. While nurse education should always be the central focus of colleges of nursing, the time has now come when we must sell our wares in a much wider marketplace. Consideration should be given to mounting multi-disciplinary courses within the health professions and to providing skills to other professions. Short courses, for instance on child abuse, could be provided for teachers in primary and secondary education. While recognizing a vast range of potential customers, this paper confines itself to education within the private sector. PMID- 8450145 TI - Application of Moos and Schaefer's (1986) model to nursing care of elderly persons relocating to a nursing home. AB - Elderly persons relocating to a nursing home experience a life transition that they usually perceive as a crisis. Effective coping with this transition/crisis requires effective management of the event. Nurses caring for these persons are challenged to assess and intervene to assist them to achieve positive outcomes from this transition. Moos & Schaefer's (1986) Conceptual Model for Understanding Life Crises and Transitions depicts a process by which nurses may help elderly persons cope effectively with relocation to a nursing home. This paper describes the model and its application to the nursing care of elderly persons relocating to a nursing home, including a case study. The extent to which the model has been empirically tested with populations in long-term care settings is critically analysed. PMID- 8450146 TI - Mobility: a concept analysis. AB - In this paper, the authors present their analysis of the concept of mobility as a starting point for the development of relevant theory. Multiple uses of the concept are considered and provisional criteria identified. Case examples, together with antecedents and consequences, of the concept are presented. Finally, research questions that would form the basis of fieldwork have been generated. PMID- 8450147 TI - Biological sciences and the nursing curriculum: a challenge for educationalists. AB - In recent years there has been considerable emphasis on the social and behavioural sciences in the nursing curriculum, with a corresponding tendency to devalue the role of the biological sciences. This paper argues the case for the biological sciences as being essential to the development of 'intelligent practitioners' and the progress of nursing. The notion of 'intelligent practice' is discussed against the background of a historical perspective which seeks to present a brief comparison of the traditional expectations of nursing practice with those for practice in the future. It is suggested that the application to nursing practice of relevant knowledge from the biological sciences is central to skillful practice and a 'caring' philosophy. Without such knowledge, nurses are unable to deliver safe, high-quality care and, in addition, 'handmaiden status' is perpetuated. In the past, the biological science component of the nursing curriculum was derived from medicine and the biomedical model: its teaching was, largely, inadequate and ineffective. If knowledge of biological science is crucial to 'intelligent practice' then there is an urgent need to review how this knowledge is structured and taught in the nursing curriculum. The conceptual model of 'bionursing' is suggested as a possible framework for developing a new approach to the structuring and teaching of biological sciences in the curriculum. Finally, consideration of biological sciences as an educational task, and the challenge of implementing a coherent, structured curriculum, are addressed. PMID- 8450148 TI - Discrepancies in aortic growth explain aortic arch gradients during exercise. AB - OBJECTIVES: This study was conducted to evaluate the incidence and etiology of hypertension and aortic arch gradients during exercise in patients who have apparent good coarctation repair assessed at rest. BACKGROUND: The reported incidence of recurrent aortic arch obstruction (rest gradient > 20 mm Hg) after previous successful surgical repair varies from 0% to 60% and usually is associated with recurrent stenosis at the site of surgical repair. METHODS: Maximal treadmill exercise with Doppler echocardiographic gradient estimation was performed in 28 patients with a good coarctation repair at rest (normal blood pressure and arch gradient < 20 mm Hg) who had isolated coarctation repair a mean of 7.8 years previously. RESULTS: Eight (29%) developed systolic hypertension for age and a mean Doppler gradient of 45 +/- 13 mm Hg. At cardiac catheterization, the rest peak to peak systolic gradient (6 +/- 6 to 28 +/- 7 mm Hg, p < 0.001), peak systolic instantaneous gradient (16 +/- 11 to 48 +/- 9 mm Hg, p < 0.01) and cardiac index (3.5 +/- 0.7 to 5.9 +/- 1.1 liters/m per m2, p < 0.001) all increased during isoproterenol infusion. Angiographic systolic aortic arch measurements proximal to the innominate artery, left common carotid artery, left subclavian artery and the narrowest dimension at the coarctation repair site demonstrated hypoplasia at the left common carotid artery (11.8 +/- 1.7 vs. 16.7 +/- 2.9 mm/m2, p < 0.01) and left subclavian artery (11.6 +/- 1.7 vs. 15.4 +/- 3.1 mm/m2, p < 0.05) compared with findings in 10 patients with normal aortograms. Transverse aortic arch ratios were also smaller in the eight patients with abnormal findings. Preoperative angiographic ratios were not predictive of late postoperative findings. CONCLUSIONS: Exercise testing detects hypertension and arch gradients in patients with a good coarctation repair as assessed at rest. The hypertension and arch "obstruction" appear to be related to discrepancies in the growth of the transverse aortic arch proximal to the repair site, rather than a "recoarctation" of the aorta. PMID- 8450149 TI - Cyclic flow variations in a conscious dog model of coronary artery stenosis and endothelial injury correlate with acute ischemic heart disease syndromes in humans. AB - OBJECTIVES: The purpose of this study was to test the hypothesis that episodes of cyclic flow variations (CFVs) in conscious dogs with coronary stenoses and endothelial injury correlate with acute ischemic heart disease syndromes in humans. BACKGROUND: Although the canine model with CFVs has proved to be a useful model of coronary thrombosis, whether CFVs progress to these syndromes has not been clearly described. METHODS: Cyclic flow variations were produced by an external constrictor placed at the site of the left anterior descending coronary artery with injured endothelium. Blood flow in this artery and 24-h Holter electrocardiogram (ECG) were recorded during the 1st 5 postoperative days. RESULTS: Of 41 dogs that underwent the initial operative procedure successfully, 29 developed an episode of CFVs. In five dogs in which CFVs persisted throughout the monitoring period, the left anterior descending coronary artery flow decreased until day 3 and thereafter increased through day 5. Transient coronary occlusion during CFVs induced ST segment changes that returned to baseline after reflow. In 12 dogs, CFVs progressed to persistent coronary occlusion, and histologic examination revealed thrombus formation at the stenotic site and evidence of myocardial infarction. Four of these 12 dogs died suddenly of ventricular arrhythmias during persistent coronary occlusion; another 5 dogs died of reperfusion arrhythmias during CFVs with no evidence of myocardial infarction. CONCLUSIONS: Conscious dogs with CFVs closely correlated with clinical acute ischemic heart disease syndromes, suggesting them to be a useful model for investigating the complex mechanisms of cellular interactions in the pathogenesis of these syndromes. PMID- 8450150 TI - Effect of stenosis geometry on the Doppler-catheter gradient relation in vitro: a manifestation of pressure recovery. AB - OBJECTIVES: This study investigated the effect of stenosis geometry on the Doppler-catheter gradient relation. BACKGROUND: Although gradient estimation by Doppler ultrasound has been shown to be accurate in various clinical and in vitro settings, there have also been reports of substantial discrepancies between Doppler and catheter gradients. These conflicting results may be due to differences in geometry and hemodynamic characteristics of flow obstructions. METHODS: Stenoses of various geometry were simultaneously studied with continuous wave Doppler and catheter technique in a well controlled pulsatile flow model. RESULTS: Doppler and catheter gradients correlated very well regardless of stenosis geometry and site of distal catheter measurement (r = 0.98 to 0.99, SEE = 1.8 to 5.3 mm Hg). When the catheter was pulled back through the stenosis, the highest gradients were found in or close to the stenosis. When these catheter gradients were compared with Doppler gradients, the agreement between the two techniques was excellent regardless of stenosis geometry (slope 0.97; mean difference 0.6 +/- 2.0 mm Hg). However, when distal pressures were measured 10 cm downstream from the stenotic segment, the slope of the regression line, and therefore the agreement between Doppler and catheter gradients, differed for the different stenosis types (slopes from 0.98 to 1.69). In stenoses with abrupt narrowing and abrupt expansion, agreement was acceptable. Doppler gradients were only slightly greater than catheter gradients (mean difference 4.5 +/- 5.2 mm Hg). In stenoses with a gradually tapering inlet and outlet, the Doppler-catheter gradient relation was dependent on the outflow angle. Good agreement was found for an angle of 60 degrees (mean difference 0.6 +/- 1.8 mm Hg). In stenoses with a 40 degrees outflow angle, Doppler gradients exceeded the catheter gradients by 13% on average; for stenoses with a 20 degrees outflow angle, Doppler gradients exceeded catheter gradients by 46 +/- 11.4%, with differences as great as 65 mm Hg. These results were identical for stenoses gradually tapering outward to the distal tubing diameter and those with abrupt expansion after 2 cm of gradual expansion. The results were also not affected by changing the inflow angle from 20 degrees to 60 degrees. However, an abrupt narrowing instead of a tapering inlet significantly altered the Doppler-catheter gradient relation (p < 0.001); Doppler gradients exceeded the catheter gradients by 34 +/- 10% for this stenosis type. CONCLUSIONS: Doppler gradients accurately reflect the highest gradients across flow obstructions that occur in the vena contracta. However, these gradients may be significantly greater than catheter gradients that are measured farther downstream, as is usually the case in clinical catheterization studies. These discrepancies are due to pressure recovery. The magnitude of pressure recovery is highly dependent on the stenosis geometry, which therefore significantly affects the Doppler-catheter gradient relation. It is the outflow geometry that predominantly influences this relation, but the shape of the inlet may affect the results as well. Although pressure recovery occurs even in stenoses with abrupt narrowing and abrupt expansion, the phenomenon is most likely to become clinically relevant in stenoses with a gradually tapering inlet and outlet with an outflow angle < or = 20 degrees. PMID- 8450151 TI - Pressure recovery distal to stenoses: expanding clinical applications of engineering principles. PMID- 8450152 TI - Increased heart rate can cause underestimation of regurgitant jet size by Doppler color flow mapping. AB - OBJECTIVES: This study addressed the hypothesis that at a constant peak flow rate, an increasing heart rate could decrease the maximal apparent jet size by Doppler color flow mapping. BACKGROUND: Recent studies have attempted to predict the severity of regurgitation from maximal jet area by Doppler color flow mapping, which correlates with flow rate for free jets at constant driving pressure and steady flow. In patients, however, maximal jet area exists for only a limited time per beat and the likelihood of visualizing it by Doppler color flow mapping depends on its duration relative to the color frame sampling rate. Increased heart rate could potentially diminish apparent jet size, particularly at slow frame rates that may not permit visualization of the maximal jet area in all beats. METHODS: This interaction was examined in pulsatile flow, holding orifice size and peak flow rate constant and varying pump pulse rate (70 to 180 beats/min) and frame rate (three rates) for jets of low and high momentum. Maximal jet area was measured in 10 consecutive beats at each pulse rate and frame rate and averaged. RESULTS: For the low momentum jet, the 10-beat average of peak jet area decreased progressively with increasing pulse rate. As pulse rate increased from 70 to 180 beats/min, maximal jet area decreased 23% at the fastest frame rate and 42% at the slowest frame rate, with prominent beat to beat variability. Jet area decreased 13% to 20% at pulse rates as low as 90 beats/min. In contrast, for the high momentum jet, maximal jet area decreased by < or = 9% from low to high pulse rate at any frame rate. CONCLUSIONS: Increased heart rate can cause underestimation of apparent jet size by Doppler color flow mapping for a given peak flow rate, particularly for jets with low momentum and delayed penetration into the receiving chamber. This observation may be relevant to acute severe regurgitation with increased heart rate in which such underestimation has been reported, as well as to right-sided lesions and children with rapid heart rates. It will also affect new techniques proposed to quantify regurgitation on the basis of velocities derived from Doppler color flow images. In practice, this effect can be reduced by increasing frame rate and selecting maximal apparent jet size at rapid heart rates and should be considered in relating jet size to the severity of regurgitation. PMID- 8450153 TI - Immediate sealing of arterial puncture sites after cardiac catheterization and coronary angioplasty using a biodegradable collagen plug: results of an international registry. AB - OBJECTIVES: The aim of this study was to evaluate the safety and efficacy of a biodegradable collagen plug that has been developed to reduce the arterial compression time required to achieve hemostasis at the arterial puncture site after diagnostic and interventional coronary procedures. BACKGROUND: After diagnostic and interventional coronary catheterization procedures, local arterial compression is required to achieve hemostasis and complications may ensue, especially in patients on full anticoagulation. METHODS: Between March 1991 and July 1991, 252 patients admitted for routine coronary angiography or angioplasty to four large hospitals received such a hemostatic device immediately after the procedure. Hemostasis was achieved with collagen in 87% of patients after a mean compression time of 4.8 min. Time to hemostasis was independent of the heparin load. A total of 54 hematomas (21%) was reported; all but 2 resolved without additional treatment. Two patients had a severe hematoma, requiring blood transfusion, and two patients required surgery to repair a pseudoaneurysm. During a follow-up period of 4 weeks no severe late complications were reported. CONCLUSIONS: We conclude that the collagen plug appears to be a safe device to achieve hemostasis at the arterial puncture site, independent of anticoagulation. PMID- 8450154 TI - Effect of balloon mitral valvuloplasty on exercise capacity, ventilation and skeletal muscle oxygenation. AB - OBJECTIVES: The short- and long-term effects of valvuloplasty on exercise capacity, ventilation and skeletal muscle oxygenation were investigated to determine whether a dissociation between hemodynamic improvement and exercise capacity occurs in patients with mitral stenosis. BACKGROUND: Percutaneous balloon mitral valvuloplasty in patients with mitral stenosis results in immediate hemodynamic improvement at rest and with exercise. Improved exercise capacity has been described at 3 months after valvuloplasty. In patients with left ventricular dysfunction, acute therapeutic interventions that produce hemodynamic benefit do not immediately improve exercise capacity. METHODS: Maximal bicycle exercise with measurement of respiratory gases was performed in 11 patients with mitral stenosis before and at 48 h and 3 months after successful percutaneous balloon mitral valvuloplasty. Respiratory and leg skeletal muscle oxygenation were assessed by monitoring changes in light absorption of the serratus anterior and vastus lateralis muscles using near-infrared spectroscopy and were expressed as percent deoxygenation. RESULTS: Mitral valvuloplasty significantly increased mean mitral valve area from 1.0 +/- 0.2 to 1.7 +/- 0.3 cm2 (p < 0.05). Immediately after valvuloplasty, peak exercise oxygen consumption (VO2), VO2 at the anaerobic threshold, ventilation, peak respiratory and leg muscle deoxygenation all remained unchanged. At submaximal work loads, respiratory muscle deoxygenation was attenuated (25 W: before 12 +/- 4%; 48 h 4 +/- 3%; 50 W: before 10 +/- 5%; 48 h 5 +/- 4%; both p < 0.05). At 3 months, significant improvement in peak VO2 (before 10.9 +/- 5%; 3 months 14.6 +/- 6.2 ml/kg per min; p < 0.05) and VO2 at the anaerobic threshold (before 7.1 +/- 2.4; 3 months 8.4 +/- 2.3; p < 0.05) were observed, whereas ventilation remained unchanged. No further improvement was seen in respiratory muscle deoxygenation. Vastus lateralis deoxygenation at submaximal work loads tended to be decreased. CONCLUSIONS: Long-term changes in skeletal muscle and the lungs preclude immediate enhancement of exercise performance after balloon mitral valvuloplasty. Immediate symptomatic improvement probably results from an immediate decrease in the work of breathing. Long-term symptomatic improvement results from changes that occur in the peripheral skeletal musculature as well as from the reduced work of breathing. PMID- 8450155 TI - Intracoronary stenting compared with conventional therapy for abrupt vessel closure complicating coronary angioplasty: a matched case-control study. AB - OBJECTIVES: A case-control analysis was performed to compare clinical outcome after intracoronary stenting with that after conventional therapy for abrupt vessel closure. BACKGROUND: Previous studies have demonstrated that stenting after abrupt vessel closure results in marked angiographic improvement and preservation of coronary flow, leading to the anticipation of similar improvement in clinical outcome. METHODS: Sixty-one of 92 consecutive patients treated at two clinical sites by intracoronary stenting for abrupt vessel closure were matched, according to angiographic features of closure and estimated left ventricular mass threatened by ischemia, with patients treated conventionally during the 18 months before stent availability. In 33 pairs of matched patients, vessel closure was established; in 28 pairs, it was threatened (coronary dissection or worsening stenosis with preservation of normal anterograde flow). Baseline clinical and angiographic characteristics were comparable in the two matched groups. Patients with indeterminate mechanisms of total occlusion (31%) or dissections < 15 mm long (43%) predominated; patients with visible thrombus (8%) or dissections > 15 mm long (18%) were infrequently represented. Stents were successfully deployed in 60 of 61 patients at a median of 52 min (range 3 to 269) after the onset of closure. RESULTS: When compared with conventional treatment, stenting resulted in less residual stenosis (26% vs. 49% diameter stenosis, p < 0.001), a greater likelihood of restoration of Thrombolysis in Myocardial Infarction (TIMI) grade 3 blood flow (97% vs. 72%, p < 0.001) and a reduction in the need for emergency bypass surgery (4.9% vs. 18%, p = 0.02). However, the incidence of Q wave myocardial infarction was nearly the same in the two groups (32% vs. 20%, respectively, p = NS). In the group with stenting, peak creatine kinase level and the frequency of Q wave infarction after established vessel closure increased with the time to stent placement (p = 0.001 and 0.054, respectively); the incidence of procedure-related Q wave infarction in patients who underwent stenting within 45 min of closure was very low (3.9%). In-hospital death occurred in 3.3% of patients in each treatment group. At a mean of 6.3 months of follow-up after hospital discharge, survival free from late cardiac death, myocardial infarction, bypass surgery or coronary angioplasty was 74.9% and 81.3% in the stent and the control treatment group, respectively (p = NS). CONCLUSIONS: Although early treatment of established vessel closure by intracoronary stenting was associated with a low incidence of both myocardial infarction and emergency bypass surgery, the likelihood or severity of infarction was not reduced among those in whom stents were implanted later. Patients with threatened vessel closure could not be shown to benefit from stent treatment. These data provide preliminary indications for stent placement in the acute period to be validated in larger randomized studies. PMID- 8450156 TI - Reliability of quantitative coronary angiography of the target lesion immediately and 1 day after coronary balloon and excimer laser angioplasty. AB - OBJECTIVES: This prospective trial was performed to evaluate the impact of the morphologic complications of angioplasty on the reliability and results of quantitative angiographic assessment of the residual stenosis. BACKGROUND: Postintervention quantitative coronary analysis is limited by a variety of such complications. METHODS: In 199 patients undergoing an early control angiographic study within 24 h after coronary balloon or excimer laser angioplasty (24-h study), detailed quantitative angiographic measurements were performed on the target lesion immediately after intervention and at the 24-h study. Reproducibility of quantitative arteriography was determined by repeat measurements on the same angiogram. RESULTS: Intraobserver/interobserver variability was significantly higher (p < 0.0001/p < 0.03) for the postintervention angiogram than for the 24-h angiogram. Patients were classified into three subgroups with respect to the occurrence of angiographic complications or chest pain after intervention. In patients with angiographic complications after balloon angioplasty alone/stand-alone laser angioplasty/laser angioplasty with adjunctive balloon dilation, a significant difference in mean minimal lumen diameter (p = 0.0001/p = 0.03/p = 0.035) was observed between the immediate postintervention and 24-h angiogram. In patients without angiographic complications or patients with recurrent chest pain undergoing balloon angioplasty, stand-alone or adjunctive laser angioplasty, mean minimal lumen diameter remained nearly unchanged (p = NS). CONCLUSIONS: Angiographic measurements of the target lesion immediately after angioplasty were significantly less reliable than measurements obtained at 24 h after angioplasty in patients with angiographic complications. The occurrence of postintervention vascular complications was associated with significant early lesion changes between the immediate postangioplasty and the 24-h angiogram. PMID- 8450157 TI - Importance of abortive shock capability with electrogram storage in cardioverter defibrillator devices. AB - OBJECTIVES: This study evaluates the ability of a third-generation cardioverter defibrillator to abort energy delivery and the importance of electrogram storage in analyzing the aborted events. BACKGROUND: In the Cadence Tiered Therapy Defibrillator, when a tachycardia satisfies detection criteria for cardioversion or defibrillation therapy, high voltage capacitors begin charging. The Cadence defibrillator continues monitoring the rhythm during charging and if the rate decreases to below the rate triggering therapy, charging is terminated. This event is registered as an aborted shock. The defibrillator also has the ability to store intracardiac electrogram recordings of the electrical events that precipitate device therapy or aborted shocks. METHODS: During a mean follow-up interval of 10 +/- 7 months, 55 aborted events were registered by the Cadence defibrillator in 18 of the 49 patients who received it. Thirty-two stored ventricular electrograms of events leading to aborted shocks were available for analysis in 15 patients. RESULTS: Intracardiac electrogram recordings demonstrated the probable electrical events leading to these aborted shocks included nonsustained ventricular tachycardia (n = 10), nonsustained rapid polymorphic ventricular tachycardia/ventricular fibrillation (n = 2), atrial fibrillation (n = 5), supraventricular tachycardia (n = 2) and electrical noise (n = 13). Eleven patients had a therapeutic intervention initiated as a consequence of the diagnostic information provided by analysis of intracardiac electrogram recordings. Four of the 15 patients had no changes made. During a follow-up period of 9 +/- 5 months after therapy was altered, no patient had subsequent aborted shocks. Five patients have had seven appropriate shocks for sustained ventricular tachycardias. CONCLUSIONS: The ability of Cadence defibrillator to continue tachycardia sensing during capacitor charging and to abort shock therapy for self-terminating events prevented unnecessary shocks in 18 (37%) of the 49 patients. Intracardiac electrogram recordings were critical for instituting appropriate therapy that may have prevented unnecessary device charging and inappropriate discharges. PMID- 8450158 TI - Radiofrequency ablation for treatment of primary atrial tachycardias. AB - OBJECTIVES: The purpose of this study was to determine the safety and efficacy of radiofrequency ablation as definitive therapy for primary atrial tachycardias. BACKGROUND: Primary atrial tachycardias are often difficult to control with antiarrhythmic medications and frequently require nonpharmacologic interventions for definitive therapy. Despite isolated reports of successful treatment of primary atrial tachycardias with radiofrequency ablation, the safety and efficacy of this technique have not been established in a larger series with long-term follow-up. METHODS: The immediate procedural success rate, associated complications and follow-up data of radiofrequency ablation were evaluated in 15 consecutive patients (11 adults and 4 children) with primary atrial arrhythmias that were refractory to medical management. RESULTS: The clinical arrhythmia was ectopic atrial tachycardia in 11 patients and sinus node reentry in 4. The site of origin of the tachycardia was in the right atrium in 14 patients and in the left atrium in 1 patient (with two distinct foci) where the local atrial electrogram preceded the onset of the P wave by 10 to 30 ms. Radiofrequency energy successfully terminated the primary atrial tachycardia in each of the patients, and all were discharged from the electrophysiology laboratory in sinus rhythm without inducible atrial tachycardia. A mean of 10.8 +/- 9.9 radiofrequency applications were delivered using 30 W of power for 30 s. The local intracardiac activation time (relative to the P wave in the surface electrocardiogram) was a mean of -21 +/- 5 ms at the successful ablation site and -15 +/- 6 ms at unsuccessful sites (p < 0.001). No complications were observed, although one patient with incessant ectopic atrial tachycardia had sinus pauses after ablation. During a mean follow-up period of 277 +/- 133 days, the clinical arrhythmia recurred in three patients (20%, 95% confidence intervals 3% to 37%) including two patients with ectopic atrial tachycardia and one patient with sinus node reentry. One of these patients was successfully treated in a second ablation session. CONCLUSIONS: Thus, radiofrequency catheter ablation appears to be a safe and effective technique for the treatment of primary atrial arrhythmias that are refractory to antiarrhythmic medications. PMID- 8450159 TI - Radiofrequency catheter ablation of ectopic atrial tachycardia using paced activation sequence mapping. AB - OBJECTIVES: Although ectopic atrial tachycardia is infrequent, it can be an important clinical challenge. We sought to define an alternative therapeutic approach to this refractory problem. BACKGROUND: Radiofrequency energy catheter ablation has been used to treat a variety of ventricular and supraventricular arrhythmias but has not been proved efficacious in the management of ectopic atrial tachycardia. METHODS: Ten patients (14 to 47 years of age) referred with refractory ectopic atrial tachycardia were studied. Mapping techniques included identification of earliest atrial activation, confirmation of concordance of P wave configuration during spontaneous tachycardia and pacing from the ablation catheter, and paced activation sequence mapping. The paced activation sequence mapping compared the activation sequence at multiple atrial sites during spontaneous tachycardia with that recorded during pacing from the ablation catheter. The catheter was steered to a point where pacing reproduced the spontaneous activation sequence. RESULTS: Foci were right atrial in eight patients and left atrial in two. In 8 of 10 patients, 514 +/- 97 (SE) J and 5.7 +/- 2.3 (SD) J radiofrequency energy applications ablated the ectopic focus. Seven of these eight patients presented with one focus and one had two discrete and stable foci. Ablation was unsuccessful in two patients with multiple foci. No complications occurred. An arrhythmia focus recurred in two patients and one patient underwent successful repeat ablation. The other patient was managed medically. All seven patients with successful ablation are symptom free after 6.5 +/- 3.8 months. CONCLUSIONS: Our preliminary experience suggests that with the use of both paced activation sequence mapping and standard techniques, radiofrequency ablation of ectopic atrial tachycardia may be a safe and effective form of therapy. PMID- 8450160 TI - Arrhythmias on the endangered list. PMID- 8450161 TI - Outcome of patients with diabetes mellitus and acute myocardial infarction treated with thrombolytic agents. The Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group. AB - OBJECTIVES: This study was designed to assess outcome in patients with diabetes who received thrombolytic therapy and to determine whether differences in angiographic characteristics may account for the worse outcome observed in diabetic patients. BACKGROUND: Patients with diabetes are known to have a worse outcome after acute myocardial infarction than that of patients without diabetes. METHODS: Clinical and angiographic characteristics of the 148 patients with diabetes and the 923 patients without diabetes in the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) trials were examined and analyzed. RESULTS: Patients with diabetes tended to be older (median age 59 vs. 56 years) and to have a higher incidence of hypertension and hyperlipidemia and a lower incidence of cigarette smoking. Patients with diabetes had significantly more severe anatomic disease (66% vs. 46% had multivessel disease, p < 0.0001), similar global left ventricular ejection fraction (49% vs. 51%) and worse noninfarct zone ventricular function (-0.13 vs. 0.32 SD/chord, p = 0.02) than that of nondiabetic patients. Angiographic patency rates at 90 min after thrombolytic therapy were similar in patients with and without diabetes (initial 90-min patency 71% vs. 70%). Diabetic patients had nearly twice the in-hospital mortality rate (11% vs. 6%, p < 0.02) and a higher incidence of pulmonary edema (11% vs. 4%, p = 0.001). Diabetic women had an especially high in-hospital mortality rate (21%). No retinal hemorrhages were observed. Although diabetes as an unadjusted variable was predictive of in-hospital (p < 0.02) and long-term (p = 0.003) mortality, after adjustment for baseline clinical and angiographic characteristics, diabetes was not found to have an independent influence on mortality. CONCLUSIONS: Patients with diabetes after myocardial infarction have a worse outcome than that of patients without diabetes despite similar rates of infarct vessel patency. However, diabetes was not found to be an independent risk factor for increased mortality. These findings suggest that diabetes itself is not a major risk factor for poor early outcome after thrombolytic therapy for myocardial infarction; rather, the secondary effects such as more extensive coronary artery disease account for the worse outcome. PMID- 8450162 TI - Differing patterns of cardiac parasympathetic activity and their evolution in selected patients with a first myocardial infarction. AB - OBJECTIVES: The purpose of the study was to compare cardiac parasympathetic activity during the early and convalescent phases of acute anterior and inferior myocardial infarction. BACKGROUND: Previous studies have shown that cardiac parasympathetic activity may vary with the site of infarction and that recovery may occur after infarction. METHODS: Cardiac parasympathetic activity was measured from 24-h electrocardiograms by counting the number of times that successive RR intervals (counts) differed by > 50 ms. Recordings began within 12 h of admission and at 7, 42 and 140 days after acute myocardial infarction in 20 patients (mean age 57 +/- 7.9 years). All patients were treated with streptokinase, aspirin and oral beta-adrenergic blocking agents. RESULTS: For the entire group, mean total 24-h RR counts increased from 592 (range 78 to 3,812) at 48 h to 648 (range 109 to 5,473) at 7 days, 1,145 (range 162 to 6,268) at 42 days and 1,958 (range 344 to 9,632) at 140 days. Patients with anterior infarction had significantly lower counts (mean 277, range 78 to 2,708; n = 11) compared with those with inferior infarction (mean 2,172, range 897 to 3,812; n = 9) at 48 h (p < 0.05). There was no significant difference in counts between patients with anterior (mean 1,051, range 212 to 6,268) and inferior (mean 1,321, range 162 to 3,265) infarction after 42 or after 140 days (anterior: mean 1,655, range 344 to 9,632; inferior: mean 2,588, range 1,700 to 5,767). CONCLUSIONS: These data suggest that after anterior myocardial infarction there is impaired cardiac parasympathetic function that improves within 6 weeks, whereas in inferior infarction there is relative preservation of cardiac parasympathetic function. PMID- 8450163 TI - Two-dimensional echocardiographic assessment of papillary muscle contractility in patients with prior myocardial infarction. AB - OBJECTIVES: This study was performed to assess the length and contractile performance of human left ventricular papillary muscles and to determine the relation between papillary muscle dysfunction and mitral regurgitation. BACKGROUND: Assessment of human papillary muscle contractility remains a clinical challenge. METHODS: Two-dimensional echocardiographic examinations were performed in 16 normal subjects and 31 patients with prior myocardial infarction. Apical echocardiograms were used to obtain long-axis views of the anterior and posterior papillary muscles. The end-systolic and end-diastolic lengths of the papillary muscles were measured and fractional shortening was calculated. RESULTS: Fractional shortening in normal subjects was 27 +/- 8% for the anterior papillary muscle and 30 +/- 8% for the posterior papillary muscle. In patients with prior myocardial infarction, a significant decrease in fractional shortening was observed in proportion to the severity of left ventricular wall motion abnormalities at the site of papillary muscle implantation. Moderate or severe mitral regurgitation was significantly more frequent in patients with combined anterior and posterior papillary muscle dysfunction than in those with isolated anterior or posterior dysfunction or with normal function of both papillary muscles (p < 0.05). CONCLUSIONS: Two-dimensional echocardiography is useful for demonstrating abnormal contractility of human left ventricular papillary muscles. Papillary muscle contractility should be analyzed in each case to elucidate the mechanism of mitral regurgitation in patients with papillary muscle dysfunction. PMID- 8450164 TI - Digital supine bicycle stress echocardiography: a new technique for evaluating coronary artery disease. AB - OBJECTIVES: The objective of this study was to determine the accuracy of digital supine bicycle stress echocardiography, a new technique for evaluating coronary artery disease during peak exercise. BACKGROUND: Prior stress echocardiographic techniques have not utilized peak exercise imaging to determine the extent and location of coronary artery disease. METHODS: Two-hundred twenty-two patients were studied: 180 underwent both supine bicycle stress echocardiography and coronary arteriography; 42 had a < 5% likelihood of disease. Forty-three patients had normal coronary arteries, 55 had single-vessel, 42 had double-vessel and 40 had triple-vessel coronary artery disease. RESULTS: Supine bicycle stress echocardiography was 93% sensitive, 86% specific and 92% accurate for identifying patients with coronary artery disease irrespective of prior myocardial infarction or achievement of > or = 85% maximal predicted heart rate. The "normalcy" rate in the low probability group was 100%. Supine bicycle stress echocardiography was 87% sensitive, 89% specific and 88% accurate for specific vessel identification. The sensitivity was greatest for the left anterior descending compared with the right coronary artery and the left circumflex coronary artery (95% vs. 81% vs. 78%, p < 0.01) and for vessels in patients with double- and triple-vessel compared with single-vessel disease (90% vs. 89% vs. 78%, p < 0.05). The procedure was significantly more sensitive for detection of vessels with 90% to 100% compared with 50% to 70% diameter stenosis (91% vs. 81%, p < 0.05) and was 88% correct in the prediction of multivessel disease. CONCLUSIONS: Supine bicycle stress echocardiography is a highly accurate tool for evaluating coronary artery disease, identifying both the patient with coronary artery disease and the location and extent of disease. PMID- 8450165 TI - Dobutamine stress echocardiography predicts surgical outcome in patients with an aortic aneurysm and peripheral vascular disease. AB - OBJECTIVES: This study was conducted to assess the utility of dobutamine stress echocardiography for determining the presence of significant coronary artery disease and for predicting surgical outcome and long-term prognosis in patients scheduled to undergo peripheral vascular or aortic aneurysm surgery. BACKGROUND: Assessment of coronary artery disease in patients scheduled to undergo peripheral vascular surgery can avoid perioperative complications. METHODS: Dobutamine stress echocardiography was performed in 98 consecutive patients scheduled to undergo aortic or peripheral vascular surgery. Intravenous dobutamine was infused in a graded fashion, with two-dimensional digital echocardiographic monitoring of ventricular function and segmental wall motion. Group 1 (n = 70) consisted of patients who exhibited a normal response to dobutamine infusion (negative dobutamine study); group 2 (n = 23) comprised those patients with an abnormal response to dobutamine, characterized by the development of new or worsening wall motion abnormalities at rest, indicating the presence of myocardial ischemia (positive dobutamine study). Five patients with an inconclusive dobutamine study (because of inadequate heart rate) were excluded from analysis. RESULTS: No major adverse effects occurred with testing in any patient. Sixty-eight of 70 patients with a negative study had peripheral vascular or aortic surgery performed without perioperative cardiac events (2 patients refused surgery). Nineteen of 23 patients with a positive study underwent coronary angiography and all had > 50% lumen narrowing in one or more major coronary artery distributions; 13 underwent coronary artery bypass grafting or angioplasty before peripheral vascular or aortic surgery and all had an uneventful perioperative period. Four of the 10 patients from group 2 who did not undergo coronary revascularization had a perioperative cardiac event (myocardial infarction in 2, an ischemic episode requiring urgent coronary bypass grafting in 1 and congestive heart failure in 1). CONCLUSIONS: Positive and negative dobutamine study results are significant predictors of the presence or absence of perioperative events (20% vs. 0%, p = 0.003). A positive test warrants coronary angiography and further medical or surgical intervention, or both, but a negative test indicates a low likelihood of perioperative cardiac complications of aortic or peripheral vascular surgery. During the long-term follow-up period in this study (group 1 mean, 24 months; group 2 mean, 15 months), two patients (3%) from group 1 and three (15%) from group 2 developed cardiac complications (p = 0.038). Thus, dobutamine stress echocardiography is safe and can predict surgical outcome in patients undergoing aortic aneurysm repair or surgery for occlusive disease of the peripheral arteries. In addition, a negative test result is a strong predictor of decreased perioperative and long-term cardiac morbidity and mortality. PMID- 8450167 TI - A cyclic breathing pattern in patients with poor left ventricular function and compensated heart failure: a mild form of Cheyne-Stokes respiration? AB - OBJECTIVES: This study was designed to evaluate the breathing patterns of patients with poor left ventricular systolic function and compensated heart failure. BACKGROUND: Cheyne-Stokes respiration is often found in patients with severe decompensated heart failure. Breathing patterns of patients with clinically moderate congestive heart failure have not been well described. METHODS: Tidal volume, oxygen consumption, carbon dioxide production, respiratory rate, minute ventilation and partial pressure of end-tidal oxygen and of end tidal carbon dioxide were measured in 36 consecutive patients with an ejection fraction < 40% and compensated congestive heart failure. Measurements were made with a computerized expiratory gas analyzer. RESULTS: Nine of the 36 patients demonstrated a cyclic breathing pattern, with a cycle length of 130 +/- 82 s. At the peak of the cycle, minute ventilation was 16.7 +/- 2.9 liters/min, tidal volume was 582 +/- 130 ml, end-tidal carbon dioxide was 25 +/- 2.7 mm Hg and end tidal oxygen was 121 +/- 4.9 mm Hg. At the nadir of the cycle, minute ventilation was 9.5 +/- 2.1 liters/min, tidal volume was 372 +/- 120 ml, end-tidal carbon dioxide was 35 mm Hg +/- 2.1 and end-tidal oxygen was 101 +/- 3.9 mm Hg. Respiratory rate was 27 +/- 5.9 breaths/min at peak and 24 +/- 5.1 breaths/min at nadir (p = NS). Patients with a cyclic respiratory pattern had a significantly lower ejection fraction (15 +/- 5%) compared with patients without cyclic respirations (26 +/- 8%; p < 0.001). There was no difference in the origin of heart failure, clinical status or exercise performance between these two groups. CONCLUSIONS: A cyclic respiratory pattern occurs commonly in patients with mild to moderate heart failure. It is related to poor left ventricular systolic function and not related to clinical status or etiology of heart failure. The cyclic respiratory pattern found commonly in patients with compensated heart failure and very poor ventricular function (ejection fraction < 25%) consists of a variation in tidal volume only. Respiratory rate is relatively constant and true apnea does not occur. PMID- 8450166 TI - A dose-response study of clentiazem, a chloro-derivative of diltiazem, in patients with stable angina. CAMCAT Study Group. AB - OBJECTIVES: The efficacy and safety of clentiazem were assessed in 199 patients with stable angina in a dose-ranging, placebo-controlled, double-blind, parallel design study. BACKGROUND: To date, this is the first large efficacy and safety study of clentiazem in patients with stable angina. METHODS: After washout and a 1-week placebo run-in period, patients received 20, 40, 80 or 120 mg/day of clentiazem tablets or placebo as a twice-daily dosage for 1 week of treatment after 1 week of dose titration. A symptom-limited exercise tolerance test was performed 4 and 12 h after dosing at the end of treatment and results were compared with baseline measurements. RESULTS: At 4 h after dosing, improvement of exercise duration from baseline value was significantly greater with clentiazem at doses of 40 mg/day (63 +/- 11 s), 80 mg/day (99 +/- 10 s) and 120 mg/day (70 +/- 11 s) than with placebo (34 +/- 10 s). Moreover, clentiazem (80 and 120 mg/day) increased the time to onset of angina and to > or = 1 mm of ST segment depression significantly more than did placebo. At submaximal exercise, clentiazem (40, 80 and 120 mg/day) decreased rate-pressure product, mainly as a result of a decrease in heart rate. At 12 h after dosing, improvement of exercise duration from baseline was significantly greater with clentiazem in doses of 80 mg/day (77 +/- 9 s) and 120 mg/day (70 +/- 10 s) than with placebo (42 +/- 9 s). The incidence of treatment-related adverse events with placebo (27%) and clentiazem (29%) was similar. The most frequently reported treatment-related adverse events with clentiazem were asthenia, headache (both 7.9%), first-degree atrioventricular block and dizziness (both 4.4%). CONCLUSIONS: The results of this short-term study suggest that clentiazem given twice daily in doses of 80 or 120 mg/day is safe and effective monotherapy in the treatment of stable angina. PMID- 8450168 TI - Trends in patient selection for heart transplantation. AB - OBJECTIVES: The purpose of this study was to review specific outcomes of patient referrals and the utility of selection criteria for heart transplantation at a single transplant center and to assess important trends over a 5-year period. BACKGROUND: Although patient selection criteria are important for the clinical success of heart transplantation and the optimal utilization of the limited supply of donor organs, there are few data regarding actual outcomes and whether selection criteria are facilitating the identification of the most appropriate patients. METHODS: We retrospectively reviewed 511 consecutive referrals of adult patients with heart failure from January 1, 1987 to December 31, 1991. Patients were followed up to one of five end points: 1) acceptance onto the transplant waiting list, 2) rejection from the transplant waiting list, 3) death, 4) referral to another program, and 5) still pending evaluation. RESULTS: Of the 511 referred patients, 221 (43%) were accepted onto the waiting list, 222 (43%) were rejected, 39 (8%) died before the evaluation was completed, 15 (3%) were referred to another program and 14 (3%) are still pending evaluation. The rates for acceptance and rejection each year ranged between 30% and 51% and there were no consistent trends in the acceptance/rejection ratio from 1987 to 1991. Of the 221 patients accepted onto the waiting list, 115 (52%) underwent transplantation, 50 (22%) died, 12 (5%) were removed from the list because of clinical improvement, 9 (4%) were referred to another program and 35 (16%) are still on the waiting list. The continuing shortage of donor organs resulted in a marked increase in the size of the waiting list from 12.6 patients in 1987 to 36.5 in 1991, as well as a marked increase in the time on the waiting list before transplantation. Over 5 years, 50 patients were considered "too well" for transplantation (23% of all rejections). Of these 50 patients, 43 (86%) are alive and 7 were lost to follow up during a mean period of 28.6 months (range 4 to 62). All 12 patients who were taken off the active transplant list because of improvement in symptoms, ejection fraction or peak exercise oxygen consumption are alive with a mean follow-up period of 27.7 months (range 11 to 61). CONCLUSIONS: These data confirm the fact that transplant referrals are a selected group of patients with a high mortality rate, as 8% died before the evaluation could be completed and 22% died while waiting for a suitable donor organ. Furthermore, patient selection criteria are able to identify a small subset of patients with a low mortality risk as patients who were rejected because they were too well or taken off the list for clinical improvement have a reasonably good prognosis. PMID- 8450169 TI - Fish oil improves endothelium-dependent coronary vasodilation in heart transplant recipients. AB - OBJECTIVES: The purpose of this study was to determine whether dietary fish oil supplementation enhances endothelium-mediated vasodilator responses in human heart transplant recipients, a group known to have coronary artery disease and endothelial dysfunction. BACKGROUND: Omega-3 fatty acid supplementation has been shown to enhance endothelium-dependent coronary vasodilation in animal models of atherosclerosis. METHODS: Endothelium-dependent vasodilator responses to intracoronary acetylcholine infusion and endothelium-independent responses to nitroglycerin were evaluated in heart transplant recipients who received a high dose of dietary supplementation with omega-3 fatty acids for 3 weeks (5 g of eicosapentaenoic acid plus docosahexaenoic acid/day, n = 7) and compared with responses in a group of matched heart transplant recipients who did not receive fish oil (control patients, n = 7). Acetylcholine was selectively infused into the midportion of the left anterior descending or left circumflex coronary artery, with the noninfused left coronary artery serving as a control vessel. Serial coronary angiograms were performed after infusion with increasing doses of acetylcholine (infused concentrations 10(-6) to 10(-3) mol/liter) and after intracoronary nitroglycerin administration. RESULTS: The patients treated with fish oil showed a normal vasodilator response to acetylcholine with 14 +/- 2.5% and 15 +/- 7% vasodilation (vs. baseline diameter) at infused acetylcholine concentrations of 10(-5) and 10(-4) mol/liter, respectively. In contrast, the control patients demonstrated vasoconstrictor responses (-1 +/- 1% and -9 +/- 4%) to acetylcholine at these same doses (p < 0.05 and < 0.005, respectively, for treated vs. control patients). There were no differences in the response to nitroglycerin between the control and treated patients. CONCLUSIONS: Dietary supplementation with fish oil significantly alters endothelium-dependent coronary vasodilation in heart transplant recipients without alteration of the responses to endothelium-independent vasodilation. Whether this enhancement of endothelial function can beneficially alter the natural history of heart transplant atherosclerosis warrants further study. PMID- 8450170 TI - Pulmonary embolism after cardiac surgery. AB - OBJECTIVES: We examined the incidence of pulmonary embolism after cardiac surgery. BACKGROUND: Because venous thromboembolism is considered to be an uncommon complication after cardiac surgery, its incidence was documented in a consecutive series of 1,033 patients who underwent cardiac surgery over a 5-year period. METHODS: Parallel cohorts of patients in a tertiary referral center were evaluated and the incidence of pulmonary embolism was compared in subgroups of patients undergoing coronary bypass surgery, valve surgery and combined procedures. RESULTS: Pulmonary embolism developed in 33 (3.2%) of the 1,033 cardiac surgical patients, within 2 weeks of a coronary bypass operation in most; it did not develop in any patient who had isolated valve replacement surgery (p < 0.05). The diagnosis of pulmonary embolism was established by pulmonary angiography in 24 patients, ventilation/perfusion lung scan in 3, postmortem examination in 5 and clinical examination in 1 patient. Important risk factors for pulmonary embolism included prolonged postoperative recovery, obesity and hyperlipidemia. The mortality rate was 18.7% in patients with in contrast to 3.3% in those without pulmonary embolism (p < 0.01). CONCLUSIONS: Although pulmonary embolism is rare after isolated valve replacement, it is not an uncommon complication after coronary bypass surgery. PMID- 8450171 TI - Relation of left ventricular mass, preload, afterload and contractility in pediatric patients with essential hypertension. AB - OBJECTIVES: The aim of this study was to determine if left ventricular preload, afterload or contractility is a correlate of left ventricular mass index in hypertensive pediatric patients. BACKGROUND: It is believed that decreased contractility and increased preload are associated with left ventricular hypertrophy in adult hypertensive patients. METHODS: Ninety pediatric hypertensive patients underwent echocardiography to assess left ventricular mass, preload (diastolic dimension and volume) and afterload (end-systolic wall stress, vascular resistance and blood pressure). Contractility was assessed by 1) the end systolic stress/volume ratio, and 2) the difference between measured and predicted velocity of circumferential fiber shortening. Univariate and multivariate analyses were performed. RESULTS: Univariate analysis showed significant correlations between left ventricular mass and 1) body mass (r = 0.33, p < 0.001), 2) black race (r = 0.37, p < 0.0003), 3) diastolic dimension (r = 0.26, p < 0.01), 4) diastolic volume (r = 0.20, p < 0.05), and 5) stress/volume ratio (r = -0.53, p < 0.0001) but not the difference between measured and predicted velocity of circumferential fiber shortening. A multivariate model included body mass, age at diagnosis, diastolic dimension, wall stress and vascular resistance but not the difference between measured and predicted velocity of circumferential fiber shortening. CONCLUSIONS: Contractility is not significantly related to left ventricular mass. The positive correlation between mass and stress/volume may be due to the dependence of the latter variable on loading conditions. We speculate that both elevated preload and systemic vascular resistance may have a role in the development of hypertrophy in hypertensive pediatric patients. PMID- 8450172 TI - Intramedullary connections of the gastric region in the solitary nucleus: a biocytin histochemical tracing study in the rat. AB - The local circuit neurons in the solitary nucleus that form part of a gastro gastric vago-vagal reflex were examined using a biocytin/avidin-peroxidase histochemical tracing method in the male Long-Evans rat. Iontophoretic deposits of very small amounts of biocytin were made into the ventral commissural nucleus of the solitary tract (vcNTS) where the excitatory neuronal response to antral distension was recorded. The tracing study revealed substantial axonal projections from the vcNTS to the immediately subjacent dorsal motor nucleus of the vagus (DMN) as well as the parvocellular reticular formation (pcRF). Some axons also appeared to terminate on neurons of the nucleus retroambiguus (nRAm) in the same coronal plane as the injection site. Labeled NTS neurons in the immediate area of the injection site revealed a clear horizontally-oriented pattern of dendrites, some of which extended from the midline to the solitary tract. Some of these dendrites could be found within the walls of arterioles, the central canal or in the area postrema. This finding suggests that vcNTS neurons activated by antral inflation are probably influenced by a number of other neural and chemical afferent signals. PMID- 8450173 TI - Regulation of acetylcholinesterase secretion from perfused bovine adrenal gland and isolated bovine chromaffin cells. AB - The secretion of acetylcholinesterase (AChE) was studied in an isolated perfused bovine adrenal gland preparation and in cultured bovine adrenal medullary chromaffin cells. Electrical field stimulation (10 Hz) of splanchnic nerve terminals in the isolated perfused gland resulted in a two-fold increase in AChE secretion from the gland. Perfusion with the cholinergic receptor antagonists mecamylamine (5 microM) and atropine (1 microM) inhibited 70% of the stimulated secretion of AChE, demonstrating that most of the stimulated secretion was derived from chromaffin cells. The effect of nicotine stimulation on the secretion of AChE from isolated bovine chromaffin cells was compared with that produced by other compounds (histamine, angiotensin II) which are known to stimulate secretion of catecholamines. Incubation with nicotine (1-25 microM) stimulated the secretion of catecholamines and AChE. Histamine (1 nM-10 microM) and angiotensin II (10 pM-10 microM) did not stimulate AChE secretion. Time course studies of AChE resynthesis after irreversible inhibition with the esterase inhibitor diisopropylfluorophosphate (DFP) demonstrated that AChE is stored within chromaffin cells for at least 11 h before being secreted. AChE secretion was inhibited within 2-3 h by 10 micrograms/ml brefeldin A (BFA), a compound known to block protein translocation from the endoplasmic reticulum (ER) to the Golgi apparatus (GA). The results suggest that AChE may reside for 8-9 h within the lumen of the ER before being actively secreted by processing through the GA. PMID- 8450174 TI - Characterization of vagal innervation to the rat celiac, suprarenal and mesenteric ganglia. AB - In order to shed light on the controversial issue of vagal innervation of the solar plexus ganglia, vagal efferent preganglionic fibers were anterogradely labeled by injecting the fluorescent carbocyanine dye Dil into the dorsal motor nucleus (dmnX). Additionally, Fluorogold was used to label the ganglia in toto, providing a counterstain and the possibility of UV light-guided dissection of the various ganglia. Using optical sectioning of whole mounted intact ganglia by means of laser scanning confocal microscopy, a considerable number of Dil-labeled vagal terminal-like structures were found in the major ganglia (celiac, superior mesenteric and suprarenal). Additionally, vagal efferent terminals were regularly found in microganglia associated with the periarterial plexuses of the celiac and superior mesenteric arteries, and in a few cases in small ganglia of the intermesenteric and renal plexuses. By using animals with prior selective vagal branch vagotomies, leaving only one (or a pair) of the three major abdominal divisions intact, it was concluded that the two celiac branches contribute the bulk of this vagal innervation, with the two gastric and the unpaired hepatic branch providing a small contribution mostly limited to the celiac ganglia. From control experiments, which involved Dil injections (1) into the dmnX in animals whose visceral afferents had been previously destroyed by capsaicin; (2) into the nodose ganglia, in order to anterogradely label vagal afferents; and (3) into the cervical vagus nerve as a control for uptake by fibers of passage, it was concluded that the identified terminal-like structures were vagal efferents and not inadvertently labeled afferents. We suggest that these vagal terminals have to be regarded either as ectopic parasympathetic junctions, or as part of a vagal mechanism for gating of sympathetic ganglionic transmission. Functionally, the parasympathetic innervation of the solar plexus may provide not only the classic vagal influence on gastrointestinal targets, but also vagal control of the adrenal glands and possibly other abdominal organs that have not been traditionally regarded as vagal targets. PMID- 8450175 TI - Altered muscle sympathetic nerve activity in hyperthyroidism and hypothyroidism. AB - To determine whether sympathetic nerve activity is altered in hyperthyroidism and hypothyroidism we microneurographically measured muscle sympathetic nerve activity in patients with these thyroid dysfunctions and compared the results with those of normal controls. Patients with hyperthyroidism tended to have less muscle sympathetic nerve activity than normal controls, and patients with hypothyroidism had significantly greater muscle sympathetic nerve activity than normal controls (P < 0.05). In all subjects, there was a significantly negative correlation between the serum concentration of free triiodothyronine or free thyroxine and muscle sympathetic nerve activity, and there was a significantly positive correlation between the serum concentration of thyroid-stimulating hormone and the muscle sympathetic nerve activity. These results suggest an inverse relationship between thyroid function and sympathetic nerve activity. PMID- 8450177 TI - Differences in electrophysiological properties between neurones of the dorsal motor nucleus of the vagus in rat and guinea pig. AB - We have examined the electrophysiological properties of neurones in the dorsal motor nucleus of the vagus (DMV) in rats and guinea pigs in transverse medullary slices maintained in vitro. There were only minor differences in the morphology of the neurones between the species, and their passive electrical properties were very similar. However, action potentials in guinea pig neurones had larger amplitudes and longer half-widths than did those in rat neurones. In both species, action potentials were followed by prolonged afterhyperpolarisations (AHPs). In the majority of guinea pig neurones, two calcium-activated potassium currents underlying the AHP could be separated into an early apamin-sensitive component and a late apamin-insensitive component. In rat neurones, the current underlying the AHP was briefer and entirely apamin-sensitive. In response to a step of depolarising current, neurones in the guinea pig only discharged once or twice and then ceased firing. In rat neurones, this manoeuvre produced repetitive firing. An inward rectifier was larger in neurones of the guinea pig than in those in the rat. The effects of 5-hydroxytryptamine and noradrenaline also differed between neurones of each species. We conclude that, despite many similarities of size and electrical properties, DMV neurones in the two species differ in terms of several voltage- and calcium-dependent conductances which determine their active electrical behaviour. PMID- 8450176 TI - Hypotensive effects of 5-HT1A receptor activation: ventral medullary sites and mechanisms of action in the rat. AB - Serotonin-1A (5-HT1A) binding sites were previously localized in several regions of the ventral medulla associated with neural regulation of the cardiovascular system. Some of these binding sites were associated with serotonergic neurons of the ventral medulla. The purpose of these studies was to assess and characterize hypotensive responses to a 5-HT1A agonist, (8-hydroxy-dipropylaminotetraline, 8 OH-DPAT), administered to the ventral medulla of the rat, to correlate the responsive ventral medullary sites with the distribution of 3H-8-OH-DPAT binding sites, and to assess the role of serotonergic systems in mediating the hypotensive responses. Ventral medullary application of 8-OH-DPAT caused dose related reductions in mean arterial pressure and heart rate which were mediated by the autonomic nervous system. The hypotensive response to 8-OH-DPAT was attenuated by pretreatment with the 5-HT1A antagonists, spiperone or NAN-190. Microinjections of 8-OH-DPAT into ventral medullary structures revealed that 8-OH DPAT responsive sites included the raphe pallidus, the parapyramidal region, and the rostral ventrolateral medulla. The role of serotonergic terminals in mediating the responses of 8-OH-DPAT was evaluated in animals pretreated with the serotonin nerve toxin, 5,7-dihydroxytryptamine (5,7-DHT). Cardiovascular responses to ventral medullary application of 8-OH-DPAT were unaffected by the selective depletion of serotonin. Thus, whereas the hypotensive responses elicited by 8-OH-DPAT in the raphe pallidus and parapyramidal region may involve serotonergic neurons, other non-serotonergic sites (e.g. the rostral ventrolateral medulla) can mediate the hypotensive actions of 8-OH-DPAT. PMID- 8450178 TI - High dose L-carnitine improves immunologic and metabolic parameters in AIDS patients. AB - Several reports indicate that systemic carnitine deficiency could occur in acquired immunodeficiency disease syndrome (AIDS), and that primary and secondary carnitine deficiency leads to critical metabolic dysfunctions. L-carnitine supplementation to peripheral blood mononuclear cells (PBMCs) of AIDS patients resulted in significant enhancement of the phytohemagglutinin (PHA)-driven proliferative response. High dose L-carnitine administration (6 gr per day for two weeks) to AIDS patients treated with zidovudine also led to increased PBMCs proliferation and reduced blood levels of triglycerides. In addition, a reduction of beta 2-microglobulin serum levels as well as circulating tumor necrosis factor (TNF)-alpha, mostly in patients exhibiting highly elevated levels, were found at the end of the treatment period. Our data suggest that in vivo L-carnitine could prove useful in ameliorating both the immune response and lipid metabolism in patients with AIDS, irrespective of initial serum carnitines levels. The mechanism(s) accounting for the observed results are currently not clear. Further studies are needed to confirm the hypothesis that L-carnitine affects the expression of HIV-induced cytokine. PMID- 8450179 TI - In vitro and in vivo immunopharmacological profile of Sch 40120. AB - Sch 40120 (10-(3-chlorophenyl) - 6,8,9,10- tetrahydrobenzo [b] [1,8] naphthyridin 5 (7H)-one) is a leukotriene inhibitor that is also a potent inhibitor of acute inflammatory responses in rodent systems. In the present study, we have evaluated the effects of this drug on immune function as well as its activity in models of immune mediated chronic inflammatory disease. Sch 40120 was particularly effective in suppressing T cell proliferative responses in vitro. Antigen specific and poly-clonally-induced in vitro antibody responses were also inhibited by the drug. However, the in vivo potency of Sch 40120 in suppressing immune responses and in inhibiting the pathological changes seen in rodent models of autoimmune disease (EAE and adjuvant arthritis) was somewhat less than that previously observed in models of acute inflammation. Nevertheless, the spectrum of activities exhibited by Sch 40120 suggests that it will be particularly useful in the treatment of psoriasis where T lymphocytes have been implicated in the development of disease and leukotrienes appear to have a role in the persistence of psoriatic plaques. PMID- 8450180 TI - Functional and histopathologic effects of rapamycin on mouse kidney. AB - The effect of rapamycin (RAPA) on kidney function and histopathology was assessed in two strains of mice. Male C3H/HeJ mice were treated with RAPA for 4 days at doses of 25, 50, 75, and 100 mg/kg, ip and male C3H/HeJ or female Balb/cJ mice were both treated for 7 days at doses of 75, 150 and 200 mg/kg. Cyclosporine (CsA) was also administered to female Balb/cJ mice at doses of 50, 100, 150 and 200 mg/kg, ip. RAPA-treated mice had elevated BUN levels but the effect was not dose-dependent and was not present in the high dose, 7-day study conducted in the C3H/HeJ mice. Body weights were significantly depressed in both of the 7 day studies but not in the 4 day study. Histopathologic examination of the kidneys revealed the presence of intracytoplasmic vacuolization in the proximal tubules in both of the 7 day studies at the higher dose only. There were no drug-related deaths. In the CsA-treated mice, multiple deaths were recorded in both the 150 mg/kg and 200 mg/kg dose groups, probably related to neurotoxicity, and BUN levels were elevated in the 100 mg/kg dose group. In conclusion, RAPA's effects on kidney function were minimal at doses 50 times higher than its therapeutic dose established in the mouse. RAPA exhibited a better therapeutic index than CsA in the mouse. PMID- 8450181 TI - In vitro phencyclidine-induced inhibition of lymphocyte proliferation: prevention by cell activation. AB - The proliferative response of phytohemagglutinin (PHA)- and interleukin 2 (IL-2) activated murine splenocytes was studied in the presence of phencyclidine (PCP), a potent psychotomimetic drug of abuse. PCP inhibited [3H]-thymidine incorporation in lymphocytes treated with PHA or IL-2. This inhibitory action was dependent upon the drug doses and the time of incubation with the cultures. There was no significant inhibitory activity of PCP when it was added 24 hrs or 48 hrs after mitogenic stimuli. Parallel, a lower inhibitory effect was observed when IL 2 or PHA were simultaneously present in the incubation medium. Moreover, the pretreatment for 18 hrs with IL-2 completely counteracted PCP-induced depression of PHA-stimulated lymphocytes. We suggest that PCP affects some pathway that regulates the activation of resting T cells rather than affecting already cycling cells. PMID- 8450182 TI - The preliminary observation on immunosuppressive effect of norcantharidin in mice. AB - Norcantharidin (NCTD) is a synthetic analog of cantharidin. It has potent antitumor properties without obvious side effect that Cantharidin has on urinary organs. It has been reported that NCTD is an immunological stimulator to NK, LAK, neutrophil and lymphocyte. In our experiment, however, we observed that NCTD can markedly inhibit lymphocyte proliferation stimulated by mitogen ConA or LPS in vitro, and the mixed lymphocyte reaction (MLR) of mice, in a dose-related manner. This occurred even when the drug was added 40 hours (for lymphocyte proliferation) or 72 hours (for MLR) after the cultures were initiated. On the other hand, NCTD has no effect on inactive lymphocytes that were cultured as control in medium without mitogens, suggesting that NCTD selectively acts on activated lymphocyte. PMID- 8450183 TI - Immunotoxic effects of mercuric compounds on human lymphocytes and monocytes. III. Alterations in B-cell function and viability. AB - The major goal of the study was to determine the effects of high and low levels of mercury on human B-cells. Following treatment of B-cells with HgCl2 (0-1000 ng) and MeHgCl2 (0-100 ng), their activation by mitogens was evaluated. Both forms of mercury caused a dose dependent reduction in B-cell proliferation in the presence or absence of monocytes. MeHgCl was approximately 10 times more potent than HgCl2. Mercury also inhibited the ability of these cells to synthesize IgM and IgG. Analysis of the expression of activation markers indicated that CD69, an early marker of cell activation, was not effected by mercury. In comparison, B cell expression of the low affinity IgE receptor and the transferrin receptor were significantly reduced. Of particular interest, cells activated by mitogen for 48 hr became refractory to the immunotoxic effects of mercury. When exposed to high levels of HgCl2 (0.5-10 micrograms/ml) and MeHgCl (0.05-1 micrograms/ml), there was minimal reduction in B-cell viability at 1-4 hr, however, after exposure to mercury for 24 hr, cell death was apparent. MeHgCl was approximately 5-10 times more potent than HgCl2. Electron microscopic analysis revealed early nuclear alterations characterized by hyperchromaticity, nuclear fragmentation and condensation of nucleoplasm. Both forms of mercury caused a rapid and sustained elevation in the intracellular levels of Ca++. The results of this investigation clearly show that mercury-containing compounds are immunomodulatory; moreover, the decrease in B-cell function indicates that this metal is immunotoxic at very low exposure levels. Furthermore, the cytotoxic events are consistent with the notion that mercury initiates changes associated with programmed cell death. PMID- 8450184 TI - New hope for the health care field. AB - Creativity is required for solving many of the problems that face the health care system. As a group, caregivers tend to underestimate their own creativity and its potential impact on the systems in which they work. This article reviews common misconceptions about creativity and describes forces that erode its expression. Suggestions are made for how creativity can be increased within traditional practice settings. Steps in a creative process are reviewed as well as internal and external factors that support the occurrence of creative moments. The benefits to be gained from increased creativity range from practical improvements within the system to personal gratification for individual caregivers. PMID- 8450185 TI - Viewing the client's world through drawings. AB - This article discusses the therapeutic use of drawings, outlines a specific drawing technique, and describes two case illustrations. Emphasis is placed on the healing quality of the drawing experience, a creative process in and of itself. These case illustrations were derived from an interpretive study in which life history and drawing methods were used to gather a holistic description about the experiences of women living with HIV disease. By making drawings depicting their illness, the ten women were offered another way to express and communicate their experiences, revealing rich descriptions that may not have been obtained by interviews alone. The drawings allowed the women to explore feelings that are often difficult to verbalize, offering additional insights about their worldview. For the practitioner, the use of drawings can therefore be a valuable tool to further understand a client, assess needs, and formulate a more inclusive approach to care. PMID- 8450186 TI - The valuing process. A vehicle for creating reality. AB - The purpose of this article is to describe the concept of valuing through defining and developing the essential elements of the valuing process. The valuing process relates to structuring the meaning of individual health. This concept is related to a nursing theory put forth by both Rogers and Parse. In addition, implications of the valuing process in nursing for quality health care are given. PMID- 8450187 TI - The missing element in health care. Humor as a form of creativity. AB - Human creativity uses what is already available, changing it in unpredictable ways. Creativity is an option to client, caregiver, and institution. It is likely to occur in the open mode of thinking, where alertness, relaxation, and playfulness coexist. Humor is a desirable avenue to creative thinking for health promotion. The release and relaxation of humor benefits client and caregiver both physiologically and psychologically. Tension eases for patients, while nurses gain a new sense of control through the use of their own sense of humor. Fifty preoperative patients were surveyed on the use of humor education as a form of stress reduction. After surgery, the patients were told one-liners prior to administration of potentially painful topical medication. All perceived less pain. Humor rooms are spaces in hospitals which encourage the therapeutic use of humor. This is a unique holistic option to promote creative thinking of the staff while it enhances the healing of the patient. PMID- 8450188 TI - Creativity in holistic nursing. PMID- 8450189 TI - The correlation between humor and the chronic pain of arthritis. AB - The purpose of this study was to examine the relationship between chronic pain and a healthy sense of humor in individuals with rheumatoid arthritis. It was hypothesized that women with a diagnosis of rheumatoid arthritis who scored higher on the sense of humor scales would have a lower score on the pain scale. Likewise, if a lower score was obtained on the humor scales, it was expected that the subject would have a higher pain score. The sample population consisted of 30 women from the Northeast section of the United States, randomly chosen, between the ages of 33 and 66 years, diagnosed with rheumatoid arthritis. The results of this study showed a significant positive correlation (r = .31, p < .01) between humor and pain, which was contrary to the stated hypothesis. Findings also showed that, except for age, there were no significant relationships between the demographic data and the subjects' perception of pain or humor. It was found that age was negatively correlated with both humor and pain. Possible reasons for the findings are discussed, and nurses are encouraged to consider all the functions of humor in working with patients. PMID- 8450190 TI - Coloring outside the lines. AB - Creativity facilitates the continuous expansion of nurses' interpretations of their nursing practice and is the essence of holistic care. In this study, the concept of creativity was explored by addressing the question, "When student nurses are given complete freedom to design nursing care for a patient, what types of activities will they include?" The students were provided with a case scenario involving a comatose Native American male patient and asked to complete an "Exercise to Stretch Your Mind." Forty-eight students completed the exercise for a total of 343 responses. Qualitative data analysis was completed, and the nursing process was used to conceptually link the patterns of interventions that emerged. These interventions involved using the sensory modalities of physical and emotional feeling, hearing, and smelling to provide contextual experiences for the patient to connect and reconnect with himself. The connecting context included six areas: the outside, his nurse, his family, his spirit, the familiar, and the future. PMID- 8450191 TI - Monoclonal antibodies to keratan sulfate immunolocalize ramified microglia in paraffin and cryostat sections of rat brain. AB - We used six monoclonal antibodies (MAb) recognizing epitopes within keratan sulfate (KS) chains for an immunocytochemical study of adult rat brain. One of the MAb selectively stained microglia and their ramified processes. KS-positive cells were found throughout the CNS in both paraffin-embedded and cryostat sections; the greatest number were present in hippocampus and brainstem. In the cortex the positive processes of some cells surrounded neuronal somata. In the white matter the processes were both parallel and perpendicular to the axon bundles. Double staining showed that KS-positive cells did not express astrocytic or oligodendroglial markers. By immunoelectron microscopy, the positivity was localized around the perikarya and cell processes of small cells with peripheral chromatin clumps and dark cytoplasm, which often contained secondary lysosomes. The KS-positive cells did not contribute to myelin sheaths and were not surrounded by a basal membrane. In addition to the cellular staining, three other MAb stained the white matter diffusely. Anti-KS MAb are therefore proposed as immunohistochemical markers for ramified microglia in both paraffin and cryostat sections of adult rat brain. PMID- 8450192 TI - Brain-derived neurotrophic factor (BDNF) peptide antibodies: characterization using a Vaccinia virus expression system. AB - We describe and characterize a series of polyclonal antibodies, generated against amino acid sequences unique to various regions within pro- and mature brain derived neurotrophic factor (BDNF), a member of the highly conserved nerve growth factor (NGF) family of neurotrophins. Synthetic peptides were coupled to carrier proteins in the presence of glutaraldehyde to restrict the host animals' immune response to epitopes that are compatible with aldehyde fixation. Initial screenings of the reactivity of the antisera were made on brain sections processed for immunohistochemistry after peptide injections into brain parenchyma. As a means of further characterizing these peptide antisera, we have evaluated the reactivity and specificity of the peptide antibodies in BHK cells expressing recombinant pro- and mature BDNF protein from a T7 RNA polymerase driven Vaccinia virus system. Several of the antibodies strongly stained components of cells transfected with the BDNF gene but did not label wild-type cells nor cells containing only the expression vector. It has also been possible to detect differential compartmentalization of the BDNF protein at various stages of processing in the BHK cells, as well as in situ in cryostat sections of brain tissue, with antisera to the pro- and mature protein. We conclude that several of our antisera recognize not only the specific peptide immunogens but also what appears to be the corresponding protein native to neurons. PMID- 8450193 TI - Localization of endothelin-1-like immunoreactivity in human placenta. AB - We examined the distribution of endothelin-1-like immunoreactivity in human placenta, using the immunoperoxidase technique. A specific polyclonal antibody to endothelin-1 was raised in rabbits, which recognized endothelin-1 and its precursor molecule, big endothelin. Immunoperoxidase staining revealed that endothelin-1-like immunoreactivity was widely distributed in the placenta. Endothelin-1-like immunoreactivity was present in endothelial cells of capillaries of the microvilli and in small- and medium-sized arteries and veins. The distribution of endothelin-1-like immunoreactivity was similar to the distribution of Factor VIII-related antigen, which stains endothelial cells. The nature of endothelin in the human placenta was further examined with cultured umbilical vein endothelial cells. Endothelial cells released endothelin-like material into the culture medium. The amount of endothelin-like material varied directly with time of incubation and the amount of fetal calf serum in the culture medium. Fractionation of the endothelin-1-like material by reversed-phase high-performance liquid chromatography (HPLC) and quantitation by radioimmunoassay (RIA) revealed that endothelin-like immunoreactivity co-eluted with endothelin-1 but not with big endothelin-1. We conclude that endothelin-1 like immunoreactivity is widely distributed in vascular endothelium of the human placenta. These data are compatible with a role for endothelin as an autocrine or paracrine modulator of vascular tone in the human placenta. PMID- 8450194 TI - Immunocytochemical identification of cell types in benign and malignant breast diseases: variations in cell markers accompany the malignant state. AB - We performed immunocytochemical staining of benign, in situ, and malignant breast disease to identify antigens related to the presence of the major parenchymal cell types of the normal breast. Markers for the epithelial cells, antiserum to epithelial membrane antigen, and three monoclonal antibodies (MAb) to milk-fat globule membranes stained most of the inner cells in benign breast lesions, carcinoma in situ, and invasive carcinomas, but the peripheral cells in benign lesions, as well as in carcinoma in situ, were unstained. MAb to epithelium specific keratin 18 stained the majority of inner cells in benign breast lesions but comparatively fewer such cells in carcinoma in situ and invasive carcinoma. Markers for the myoepithelial cells, antisera, and MAb to smooth muscle actin and vimentin stained most of the peripheral cells in benign breast lesions and in carcinoma in situ but failed to stain virtually any neoplastic cells in invasive carcinomas. Markers for the basement membrane adjacent to the myoepithelial cells, antiserum, and MAb to laminin and Type IV collagen delineated an intact basement membrane around benign lesions and carcinoma in situ, and fragmented structures in 5-10% of invasive carcinomas; the remaining carcinomas were largely unstained. Markers for both myoepithelial and epithelial cells, keratin MAb PKK2 and LP34, stained most of the inner cells in benign lesions but usually only relatively few malignant cells in carcinoma in situ and invasive carcinomas. Markers for the secretory alveolar cell, MAb to beta- and kappa-casein, stained a few isolated cells in benign lesions, many more inner cells in two such lesions in pregnant females, and none in invasive carcinomas. In conclusion, the myoepithelial cell and, under suitable hormonal conditions, the secretory alveolar cell, are retained in most benign lesions, but they are largely lost in invasive carcinomas. PMID- 8450196 TI - Cytochemical localization of carbohydrate residues in microfilariae of Wuchereria bancrofti and Brugia malayi. AB - We investigated the localization of carbohydrate residues on the surface structures of microfilariae of Wuchereria bancrofti and Brugia malayi, using a panel of 10 different gold-labeled lectins and chitinase. The sheath, a structure that encloses the microfilariae, is not a homogeneous structure, presenting two clearly distinct layers. The outer layer is more electron dense and was not labeled with the lectins. The inner layer is less dense and was intensely labeled with lectins, especially those that recognize D-galactose and N-acetyl-D galactosamine. Small differences were observed in the lectin labeling pattern of microfilariae of W. bancrofti and B. malayi. D-galactose and fucose were observed in the cuticle of both species. Chitin, as revealed with gold-labeled chitinase, was observed in the cuticle of microfilariae of W. bancrofti but not in B. malayi. PMID- 8450195 TI - Enhanced carbodiimide fixation for immunohistochemistry: application to the comparative distributions of N-acetylaspartylglutamate and N-acetylaspartate immunoreactivities in rat brain. AB - To improve carbodiimide-based immunohistochemistry, carbodiimide-mediated coupling of radiolabeled N-acetylaspartylglutamate (NAAG) to bovine serum albumin was assayed in vitro. Various perfusion protocols, based on assay results, were tested for their ability to improve the immunohistochemical localization of two nervous system-specific molecules, NAAG and N-acetylaspartate (NAA) in the spinal cord, medulla, hippocampus, and cerebral cortex of the rat. Coupling of [3H]-NAAG to BSA in vitro was optimal with 100 mM carbodiimide and 1 mM N hydroxysuccinimide in water at 37 degrees C. Optimal fixation of tissue was defined as permitting the identification of the NAAG and NAA in neuronal somata, dendritic arborizations, fine axons, and synaptic terminals with minimal diffuse background immunoreactivity. These conditions were obtained at 37 degrees C with 6% carbodiimide, 1 mM N-hydroxysuccinimide, and 5% dimethylsulfoxide perfused transcardially. Strong NAAG and NAA immunoreactivities were co-distributed in the majority of neurons in the spinal cord. Large-diameter spinal sensory afferents were stained for NAAG in the dorsal horn. The dorsal column nuclei were immunoreactive for NAAG and NAA, but only NAA staining was observed in the nucleus of the solitary tract. In cerebral cortex and hippocampus, NAAG and NAA immunoreactivities appeared to be exclusive, with NAAG staining observed in interneurons throughout all cortical layers, and NAA immunoreactivity present in most pyramidal neurons. PMID- 8450197 TI - Quantitative immunohistochemistry in the rat facial nucleus with [125I]-iodinated secondary antibodies and in situ autoradiography: non-linear binding characteristics of primary monoclonal and polyclonal antibodies. AB - Indirect immunohistochemistry is an important routine method in histology and histopathology. Here we have investigated the quantitative aspects of antibody binding to tissue sections, using a range of monoclonal and polyclonal antibodies and the regenerating rat facial nucleus as the experimental model. The in situ binding of primary antibodies was quantified using appropriate [125I]-iodinated secondary antibodies and quantitative autoradiography. The majority of primary antibodies revealed an apparently bell-shaped curve of in situ antibody binding, with the binding increasing up to a specific antibody concentration and then decreasing; similar data were also obtained with enzymatic immunohistochemistry. There was also a close correlation between the quantitative changes in antibody binding during the time course of facial nerve regeneration and those observed with enzyme histochemistry. PMID- 8450198 TI - Extracellular matrix in regenerating rat sciatic nerve: a comparative study on the localization of laminin, hyaluronic acid, and chondroitin sulfate proteoglycans, including versican. AB - Using a glial hyaluronate-binding protein as a probe, monoclonal antibodies against versican and ABC digested chondroitin sulfate proteoglycans, and polyclonal antibodies against laminin, we localized these extracellular matrix (ECM) components in the endoneurium of the adult rat sciatic nerve. During Wallerian degeneration caused by nerve crushing, the staining pattern of these ECM elements changed dramatically. In the first stages and up to 5 days after injury, the tubular endoneurial structures remained the same as in control nerves. Ten days after crush, the bands of Bungner formed by proliferating Schwann cells in the distal stump of crushed nerves stained diffusely for hyaluronate, laminin, and chondroitin sulfate. Regenerating axons were demonstrated in this location by double-labeling experiments with neurofilament antibodies. Conversely, staining with antibodies against versican, a hyaluronate binding proteoglycan, was reduced and the bands of Bungner were not stained. After 30 days the endoneurial tubes made their reappearance and, as in normal nerve, they stained for hyaluronate, laminin, versican, and chondroitin sulfate. It is concluded that proliferating Schwann cells in peripheral nerve undergoing Wallerian degeneration are capable of producing several endoneurial ECM constituents, versican being a notable exception. PMID- 8450199 TI - Binding of bacterial endotoxins to the macrophage surface: visualization by fracture-flip and immunocytochemistry. AB - Endotoxins (lipopolysaccharides, LPS) are surface components of gram-negative bacteria that stimulate macrophage activation and cause endotoxic shock. How LPS is recognized by host cells is still an open question, but it is generally accepted that many effects of endotoxins follow the overproduction of cytokines by macrophages. In the present study, we used fracture-flip and immunolabeling to study the morphology of isolated commercial LPS (C-LPS), the endotoxin release from the bacterial wall in presence of serum (S-LPS), and the distribution of these two endotoxins on the macrophage surface. Cells treated with C-LPS exhibited large LPS aggregates bound to smooth and particulate areas of the membrane and to microvilli. In contrast, macrophages incubated with S-LPS showed a uniform monodispersed labeling over the free surface of the membrane. Our results show that fracture-flip provides high-resolution images of the binding of ligands to the cell surface. They also suggest the importance of using highly dispersed LPS suspensions when the mechanisms of cell activation and damage by endotoxins are studied. PMID- 8450200 TI - Solubility of cytoskeletal proteins in immunohistochemistry and the influence of fixation. AB - For accurate and quantitative immunohistochemical localization of antigens it is crucial to know the solubility of tissue proteins and their degree of loss during processing. In this study we focused on the solubility of several cytoskeletal proteins in cat brain tissue at various ages and their loss during immunohistochemical procedures. We further examined whether fixation affected either solubility or immunocytochemical detectability of several cytoskeletal proteins. An assay was designed to measure the solubility of cytoskeletal proteins in cryostat sections. Quantity and quality of proteins lost or remaining in tissue were measured and analyzed by electrophoresis and immunoblots. Most microtubule proteins were found to be soluble in unfixed and alcohol fixed tissues. Furthermore, the microtubule proteins remaining in the tissue had a changed cellular distribution. In contrast, brain spectrin and all three neurofilament subunits were insoluble and remained in the tissue, allowing their immunocytochemical localization in alcohol-fixed tissue. Synapsin I, a protein associated with the spectrin cytoskeleton, was soluble, and aldehyde fixation is advised for its immunohistochemical localization. With aldehyde fixation, the immunoreactivity of some antibodies against neurofilament proteins was reduced in axons unveiling novel immunogenic sites in nuclei that may represent artifacts of fixation. In conclusion, protein solubility and the effects of fixation are influential factors in cytoskeletal immunohistochemistry, and should be considered before assessments for a quantitative distribution are made. PMID- 8450201 TI - Cholesterol ester in corpus luteum of rat observed by analytical color fluorescence electron microscopy. AB - We used an analytical color fluorescence electron microscope to observe cathodoluminescence (CL) in the corpus luteum of rat. CL was emitted from lipid droplets and has a typical spectrum of two peaks at wavelengths of 320 and 430 nm. The intensity of CL at 320 nm (CL320) in the corpus luteum showed a regular change during an estrous cycle: it was very weak at the newly formed stage, gradually increased, reached the maximum at diestrus 2, and then began to diminish at proestrus except in the patches of degenerated cells. CL320 decreased during early stages of pregnancy or after prolonged treatment with 4 aminopyrazolo-pyrimidine; CL at 430 nm (CL430) remained clearly visible. CL320 showed a strong emission from degenerated luteal cells 10 days after hypophysectomy, but was diminished in cells rescued by injection of 50 IU pregnant mare's serum gonadotropin. In the luteal cells of luteinized ovary 2 hr after intravenous injection of 10 IU luteinizing hormone, CL was barely detected. CL320 in interstitial cells was also weak in the rats hypophysectomized and then treated with pregnant mare's serum gonadotropin, and in the 4-aminopyrazolo pyrimidine-treated rats, although it has little change through a natural estrous cycle. The results are consistent with the assumption that the content of cholesterol ester is reflected by the intensity of CL320 emitted from the lipid droplets of rat luteal cells. The possibility was shown that the condition of steroidogenesis can be monitored through CL analysis by microscopy. PMID- 8450202 TI - A simple method for immunofluorescent double staining with primary antisera from the same species. AB - We have developed a new double immunofluorescence technique by which two neuroactive substances in the same tissue section can be labeled with primary antisera raised in the same species. The optic lobes of the locust Schistocerca gregaria were used as a model system to develop the staining procedure. FMRFamide immunoreactive neurons were detected by rabbit antisera against FMRFamide and FITC-conjugated secondary antibodies. Antibodies against the second peptide, pigment-dispersing hormone (PDH), also raised in rabbit, were biotinylated and detected via streptavidin-Texas Red. Crossreactivity of the PDH immunoglobulins with the FITC-conjugated secondary antiserum was prevented by pre-incubation with rabbit gamma globulins. The two peptide immunoreactivities could be conveniently observed on the same section with the different fluorescent markers. This double labeling technique with modified antibodies is easily performed and highly useful for co-localization studies with antisera raised in the same species. PMID- 8450203 TI - A photocross-linking fluorescent indicator of mitochondrial membrane potential. AB - Ionic dyes that distribute across membranes according to electrical potential have proven valuable as fluorescent indicators of mitochondrial energetics in living cells. Applications have been limited, however, as potential-dependent staining is lost during cell fixation. We have produced a membrane potential indicator whose potential-dependent distribution can be made permanent, to enable correlation of membrane potential with cytochemical information from immunofluorescence. A carbocyanine dye was derivatized with a photoreactive nitrophenylazide moiety so that irradiation would induce nonspecific, covalent attachment to nearby molecules. Photo-induced cross-linking was observed in paper chromatography, when irradiation caused immobilization of the dye. The new dye, named PhoCy (photofixable cyanine), showed specific staining of mitochondria in living Swiss 3T3 fibroblasts. When living cells were stained, irradiated, and fixed with formaldehyde, mitochondrial staining was retained owing to cross linking with mitochondrial components. Omission of irradiation eliminated mitochondrial staining in fixed cells. Labeling, irradiation, and fixation procedures were optimized to produce bright specific staining with minimal background. The indicator's sensitivity to mitochondrial potential was demonstrated by treating cells with 2,4-dinitrophenol, an uncoupler of mitochondrial electron transport, which decreased mitochondrial staining in living cells and in the corresponding fixed specimens. PMID- 8450204 TI - Inhibition of IL-2-dependent proliferation by a prostaglandin-dependent suppressor factor. AB - In the picryl chloride contact sensitivity system in mice, i.v. injections of trinitrobenzene sulfonic acid (TNBSA) prevents elicitation of delayed-type hypersensitivity reactions. This suppression is due in part to a non-specific, PG dependent factor (TNBSA-F) that is induced by i.v. injection of TNBSA and is produced by pooled spleen and lymph node cells in vitro. Inasmuch as a role for lymphokines such as IL-2 has been postulated in delayed-type hypersensitivity, we determined the in vitro effects of TNBSA-F on the responsiveness of HT-2 target cells to IL-2. TNBSA-F induced a dose-dependent unresponsiveness of HT-2 cells to IL-2. The inhibitory activity was not present in supernatants from lymphoid cells of sham-treated mice. In the presence of indomethacin, spleen, and lymph node cells from TNBSA-immunized mice produced a factor whose activity was much reduced compared to TNBSA-F. This suggested that PG were required for TNBSA-F activity. However, PG alone did not induce the unresponsiveness because TNBSA-F but not sham-treated mice had inhibitory activity despite containing similar levels of PGE2. Rather, the combination of i.v. TNBSA injections and PG synthesis during production of TNBSA-F were required to produce a suppressive TNBSA-F. The inhibitory effect of TNBSA-F was not due to the presence of transforming growth factor-beta, soluble immune-response suppressor, INF-gamma, or JE in the factor preparation. Partial characterization showed a single peak of in vitro TNBSA-F activity (molecular mass approximately 35-55 kDa) by Sephadex G-200 gel filtration chromatography and by HPLC. In addition, TNBSA-F retained its activity after multiple cycles of freeze-thaw and heating for 1 h at 56 degrees C. The inhibitory effects of TNBSA-F on IL-2-induced proliferation suggest that suppression of delayed type hypersensitivity after i.v. administration of TNBSA may, in part, be due to a PG-dependent suppressor factor that inhibits the responsiveness of target cells to IL-2. PMID- 8450205 TI - Distinction of mouse CD8+ suppressor effector T cell clones from cytotoxic T cell clones by cytokine production and CD45 isoforms. AB - Mouse CD8+ T cell clones could be subdivided into two subgroups by the pattern of cytokine production and CD45 isoforms that exactly corresponded with the functionally assigned cytotoxic (CTL) and suppressor (Ts) subsets. All the Ts clones invariably produced IL-10 after stimulation with immobilized anti-CD3, whereas none of CTL clones expressed mRNA of IL-10 by the same stimulation. All the CTL clones were positive for CD45RA Ag, a product of exon 4 of CD45 gene, whereas none of the Ts clones were positive for this Ag. The results are analogous to the situation within CD4+ T cell clones in which Th1 and Th2 subtypes can be distinguished by CD45 isoforms and cytokines they produce. Ts clones could suppress the proliferative responses of both Th1 and Th2 type CD4+ clones by the production of two different cytokines, IL-10 and IFN gamma, respectively, but none of the CTL clones could suppress the proliferation of CD4+ T cells. The participation of an additional nonspecific molecule in the suppression of antibody response is suggested. PMID- 8450206 TI - Induction of differentiation in a B lymphoma X B lymphocyte hybrid line. II. Intraclonal heterogeneity in growth, secretion of IgM, and cytokine production in response to lipopolysaccharide. AB - Murine B lymphocyte clones have proven to be useful models to study aspects of B lymphocyte growth and development. It had been previously shown that induction of TH2.2 (B lymphoma X B lymphocyte) with LPS resulted in differentiation into IgM secreting cells (a feature similar to other B cells lines such as BCL1), and secretion of granulocyte-macrophage-CSF. Many transformed and nontransformed lines (including TH2.2) have been shown to generate progeny heterogenous in size and secretion of product when exposed to mitogen. We extend this study to demonstrate heterogeneity in secretion of IgM, granulocyte-macrophage-CSF, IL-3, and IL-6 in LPS-induced TH2.2. Clones generated by limiting dilution were heterogenous with respect to size, type, and quantity of product secreted. Microscopic clones ranged from 10 to about 1000 cells in size and could not be grown further; the majority secreted one product (mainly IgM). These clones were very efficient secretors of IgM and probably consist mainly of terminal-secreting cells. Microscopic clones secreting cytokine were also efficient producers. Visible clones from LPS-induced cultures grew to the same size as uninduced clones and were often restricted in secretion of products. Although the majority secreted three of four products (52%), many secreted IgM only or IgM and one cytokine. Although there was a strong tendency for clones to secrete multiple products, almost every secretory phenotype could be found. Amounts of different products secreted were not correlated, suggesting an additional level of independent control of this variable. Restriction of secretion was not due to genetic variation because visible clones originally restricted in secretion almost always produced all products when expanded and retested. These findings indicate that cells of TH2.2 were heterogeneous with respect to growth and secretion in the presence of LPS and were individually programmed for differentiative responses. The programming of cells was not permanent, but subject to dynamic change. PMID- 8450207 TI - Accessory cell function of keratinocytes for superantigens. Dependence on lymphocyte function-associated antigen-1/intercellular adhesion molecule-1 interaction. AB - A growing body of evidence points to a role for epidermal keratinocytes as active participants in immunologic reactions. Inasmuch as certain T cell-mediated skin diseases, such as psoriasis and atopic dermatitis, are triggered by microbial infection, we asked whether multipassaged human keratinocytes could provide the costimulatory signals necessary to induce autologous T cell proliferation in response to bacterial-derived super-antigens. On exposure to IFN-gamma, keratinocytes are induced to express HLA-DR and HLA-DQ class II MHC Ag, and the lymphocyte function-associated Ag-1 counter-receptor intercellular adhesion molecule-1 (ICAM-1). This change in keratinocyte phenotype is accompanied by the ability of these cells to support T cell proliferation induced by two different bacterial-derived superantigens, staphylococcal enterotoxins A and B. Superantigen-driven proliferation in the presence of IFN-gamma-treated keratinocytes was significantly inhibited (70-90% reduction) by mAb against the LFA-1 alpha- or beta-chain or ICAM-1. Proliferation was not inhibited by mAb against the CD28 ligands BB-1 or B7, even though these keratinocytes express BB 1. In addition to previous defined roles for class II MHC Ag, stimulation of LFA 1 on the T cells by ICAM-1 on the keratinocytes also plays an important costimulatory role in this superantigen-mediated response. The accessory cell capability of keratinocytes was not unique to superantigen driven responses as PHA, as well as anti-CD3 mAb also induced vigorous T cell proliferation when IFN gamma-treated keratinocytes were added. However, IFN-gamma-treated keratinocytes consistently failed to provoke an allogeneic response. These data demonstrate that 1) keratinocytes can serve as accessory cells for T cell proliferation using a variety of different stimuli, 2) the LFA-1/ICAM-1 interaction plays a major role in keratinocyte-mediated costimulation, and 3) previous reports in which IFN gamma-treated keratinocytes failed to support T cell proliferation to nominal or alloantigens, may reflect impaired Ag presentation via class II MHC molecules, rather than lack of necessary costimulatory signals. These findings highlighting the accessory cell function of keratinocytes may have implications for our understanding of the pathogenesis of immunologic disorders of the skin. PMID- 8450208 TI - Use of bispecific heteroconjugated antibodies (anti-T cell antigen receptor x anti-MHC class II) to study activation of T cells with a full length or truncated antigen receptor zeta-chain. AB - Ligand-induced activation of T cells involves recognition of monovalent peptide Ag complexed with a cell surface MHC-encoded molecule. In contrast, antibody induced activation of T cells typically requires external cross-linking of the TCR. To examine the mechanisms that underlie the ability of these different stimuli to signal, we have created bispecific chimeric antibody molecules (BA) that mimic Ag in several important aspects. Anti-TCR-alpha, -beta, or anti-CD3 epsilon Fab fragments were covalently coupled to an anti-MHC class II Fab fragment. These BA elicited IL-2 production or proliferation from Ag-specific T cell hybridoma cells or splenic T cells, respectively, in the presence, but not the absence, of accessory cells expressing the appropriate MHC class II molecule. This response was prevented by soluble blocking antibodies against the TCR or MHC class II. When "presented" by MHC class II-bearing accessory cells, anti-TCR x anti-MHC class II BA, like cell surface Ag, elicited IL-2 production from T cell transfectants expressing full length TCR zeta-chain but not from otherwise identical cells expressing truncated zeta; when immobilized on a plastic surface these BA were potent stimulators that induced equal amounts of IL-2 from the same cells. Purified Ag/MHC complexes immobilized on plastic were able to induce IL-2 production from T cells expressing the full length, but not the truncated, form of zeta. We hypothesize that TCR-mediated T cell activation requires stable aggregation of the TCR. In this model, activation by mobile cell surface Ag/MHC or BA occurs in two steps, occupancy-induced TCR clustering followed by stable aggregation facilitated by the presence of a full length zeta-chain. Immobilized high affinity anti-TCR antibodies, but not low affinity Ag/MHC complexes, directly promote stable receptor aggregates, and thus would not require a full length zeta-chain. PMID- 8450209 TI - cis-dominant regulation of CD4 and CD8 gene expression in rat/mouse T cell heterohybridomas. AB - To determine whether expression of CD4 and CD8 molecules on T cells is determined solely by transacting regulators, we examined heterohybridomas derived from the fusion of a rat CD4+ T cell line and the CD4- CD8- mouse thymoma BW5147. The majority of hybrid offspring expressed rat CD4. However, a fraction of the cell lines obtained expressed not only rat CD4 but also various amounts of mouse CD4 and CD8 molecules from both species. Cloning of two of these heterogeneous lines revealed that expression of all four Ag varied not only between different clones but also within clonal populations. The expression of Ag not present on the parental cells suggested an alteration in the normally stable regulatory mechanisms present in those cells. Moreover, a lack of concordant expression between the rat and mouse loci was observed, indicating that active and silent homologous loci can exist together in single nuclei. Expression of CD4 and CD8 in these cells, therefore, cannot be solely mediated by trans-acting diffusible regulators but must also depend on cis-dominant effects on the loci themselves. The phenotypic heterogeneity of clonal populations was found to result from unpredictable shifts, both positive and negative, in the expression of CD4 and CD8 over time, indicating that the cis-dominant effects were only quasistable. Preliminary examinations of the density of 5-methylcytosine within the CD4 and CD8 loci in various phenotypic populations separated by FACS from within heterogeneous clones revealed a correlation between surface expression of the mouse CD8 protein and a lack of methylation around the mouse CD8 gene. In contrast, the CD4 gene remained extensively methylated regardless of its surface expression. PMID- 8450211 TI - HLA-DQ allelic polymorphisms constrain patterns of class II heterodimer formation. AB - HLA-DQ class II molecules are complex heterodimers in which polymorphic alpha- and beta-polypeptides form noncovalent associations leading to cell surface expression. Using gene transfer with retroviral vectors, we demonstrate that surface expression of heterodimers among various DQ alpha and -beta polypeptides is not universal. Two types of allele-specific constraints were found: DQ beta chains that are associated with the DQw1 specificities do not form stable cell surface heterodimers with DQ alpha chains encoded on haplotypes that are associated with DQw2, DQw3, or DQw4. Similarly, surface expression of heterodimers composed of DQw2- or DQw3-associated DQ beta chains and DQw1 DQ alpha chains were not detected. The formation of mixed isotype heterodimers also showed allelic preference: DR alpha/DQw1 beta dimers were detected on the cell surface, but DR alpha/DQw3 beta dimers were not. Failure to express class II heterodimers on the cell surface was apparently due to either inefficient assembly of the alpha- and beta-chains or retention of the mismatched dimers in an intracellular compartment. DQ beta cDNA encoding DQw1- and DQw3-associated beta-polypeptides were modified to create chimeric expression vectors in which portions of the DQ beta polypeptides were exchanged between different alleles. The resulting chimeric DQ beta polypeptides were tested for their ability to form stable heterodimers with different DQ alpha polypeptides. A cluster of polymorphic amino acid residues encoded by the 3' end of the DQB1 second exon, corresponding to residues 60 to 91 in the DQ beta polypeptide, were found to be critical determinants constraining stable cell surface heterodimer formation among preferential alpha- and beta-combinations. PMID- 8450210 TI - Multiple B29 containing complexes on murine B lymphocytes. Common and stage restricted Ig-associated polypeptide chains. AB - The B29 gene is specifically expressed in all cells of the B lymphocyte lineage, and the B29 protein is disulfide-linked to the protein product of at least one other gene, known as mb-1. The noncovalent association of these heterodimers with Ig H chains is thought to be required for surface expression and signal transmission by B cell Ag receptors. We now demonstrate by two-color immunofluorescence a direct correlation between B29 density and surface Ig expression on normal spleen and bone marrow cells. The proportion of B29 in Ag receptor complexes appears to be relatively constant across major B lymphocyte subpopulations. Multiple B29-containing heterodimers were resolved on normal spleen cells by surface labeling, immunoprecipitation, two-dimensional gel analysis, and immunoblotting. As with lymphoma cells in our earlier study, the conditions of detergent extraction were critical to detection of certain species. Many laboratories have observed a family of 69- to 85-kDa heterodimers that are extracted with digitonin. These species are clearly Ig-associated, and are coprecipitated with anti-Ig antibodies. We found that extraction with Triton X 100 revealed an additional pair of 52- to 58-kDa heterodimers, where B29 was disulfide-bonded to a protein of approximately 23 kDa. The latter was detectable by immunoblotting with antibodies to extracellular, but not cytoplasmic, portions of mb-1. We found that, with mature cells, both conventional and low molecular mass heterodimers were solubilized with digitonin, but only detectable if Triton was present during immunoprecipitation. Thus, a protein having partial serologic identity with mb-1 forms heterodimers that are cryptic on splenic B cells, and possibly not directly associated with surface Ig molecules. In contrast, both types of heterodimers were readily detectable on late stage pre-B cells, regardless of detergent used for extraction or antibody used for immunoprecipitation. In that situation, both low- and high molecular mass heterodimers were associated with surface Ig. These findings increase our understanding of the B lymphocyte Ag receptor complex and indicate that its components may change as a function of differentiation. PMID- 8450212 TI - Murine C4b-binding protein. Mapping of the ligand binding site and the N-terminus of the pre-protein. AB - We have constructed cell surface-bound forms of murine C4b-binding protein (mC4BP) that allowed us to monitor the binding of mC4BP to C4b with relatively simple erythrocyte rosette assays. We used two types of surface-bound mC4BP: one in which segments of mC4BP were fused directly to a peptide containing the transmembrane and cytoplasmic domains of human complement receptor CR2 (BPR1 type); and a second in which the same segments were fused to a longer peptide containing the five membrane-proximal short consensus repeats (SCR) of CR2 as well as the transmembrane and cytoplasmic domains (BPR2-type). COS cells transfected with either construct carrying all six mC4BP SCR rosetted with C4b bearing EAC14 cells but not with C4b-lacking EAC1 cells; and rosetting was inhibited by excess inactivated C4 but not inactivated C3. COS cells transfected with BPR2 constructs carrying only SCR 1-3 or 1-4 gave similar rosetting behavior. However, rosetting was not observed with BPR2 constructs carrying only SCR 1-2 or 2-6, or with BPR1 constructs carrying only SCR 1-2, 1-3, 1-4, or 2-6. Finally, we found that alteration of the AUG sequence 56 triplet codons upstream of the putative N-terminus of mature mC4-BP eliminates rosetting whereas alteration of a second AUG sequence 13 codons upstream has no effect on rosetting. These results indicate that 1) SCR 1-3 of mC4BP are necessary and adequate for binding to C4b, 2) steric effects close to the cell surface may interfere with binding, and 3) mC4BP has an extraordinarily long 56 amino acid residue signal peptide. PMID- 8450213 TI - T cell retargeting using bispecific monoclonal antibodies in a rat colon carcinoma model. II. Syngeneic colon carcinoma CC531 is efficiently killed by retargeted cytotoxic T lymphocytes in vitro despite limited lysis in 51Cr release assays. AB - We have previously described the generation of bispecific anti-TCR*anti-tumor mAb, intended for in vivo analysis of T cell retargeting in a syngeneic rat colon carcinoma model. Colon carcinoma CC531 proved to be markedly resistant to lysis by polyclonally activated, retargeted rat T lymphocytes, if measured in short term or overnight prolonged 51Cr release assays. Using cocultivation, we have now focused on another, biologically more relevant aspect of retargeted interaction: the effect on the capacity of CC531 tumor cells to survive and grow. Tumor neutralization was scored after 3 days of coculture, using a tetrazolium salt to quantify viable adherent tumor cells. Compared to 51Cr release assays, we found cocultivation to be more sensitive and more informative, as it revealed tumor cell killing at low E:T ratios, synergism of bispecific antibodies and exogenous IL-2, and free bispecific antibody-dependent recycling of effector cells. Apart from providing valuable information for future in vivo studies in this model, these data support the notion of tumor neutralization as a useful alternative for 51Cr release assays. PMID- 8450214 TI - T cell-dependent IFN-gamma exerts an antiviral effect in the central nervous system but not in peripheral solid organs. AB - The antiviral relevance of soluble mediators that may operate in the vicinity of virus specific effector T cells was investigated. Mice were immunized with vesicular stomatitis virus (VSV) wild type (wt) and subsequently challenged with a mixture of two vaccinia recombinant viruses, one expressing the nucleoprotein of VSV (vacc-VSV-NP) the other expressing the glycoprotein of lymphocytic choriomeningitis virus (vacc-LCMV-GP). It was determined whether or not the VSV wt-induced memory T cell response that is protective against vacc-VSV-NP would inhibit growth of the nonrecognized vacc-LCMV-GP. In ovaries and testes replication of vacc-LCMV-GP was not inhibited. In contrast, the T cell response against vacc-VSV-NP nonspecifically inhibited growth of the non-recognized vacc LCMV-GP in the central nervous system. This inhibiting effect was partly abrogated by treatment with anti-IFN-gamma antiserum but not by an anti-TNF-alpha antiserum. Similar results were obtained in VSV wt-immune H-2b mice, which eliminate vacc-VSV-NP by CD8+ T cells and in H-2k mice, which eliminate vacc-VSV NP by a CD4+ T cell-dependent mechanism. These data suggest that a protective bystander effect mediated by soluble CD8+ and CD4+ T cell-dependent factors may be demonstrated against vaccinia virus only in an organ such as the central nervous system in which the blood-brain barrier inhibits diffusion and draining of the soluble antiviral factors released by specific effector T cells. PMID- 8450215 TI - Pure protein from Leishmania donovani protects mice against both cutaneous and visceral leishmaniasis. AB - A protein purified from Leishmania donovani promastigotes, dp72, was shown to partially protect BALB/c mice against a challenge by this parasite. Immunized mice infected i.v. with 10(7) L. donovani promastigotes showed a 0, 60, and 78% reduction in liver parasite burden compared with the control mice at each time point examined after challenge, 1, 20, and 108 days, respectively. Western blotting demonstrated that the sera from the immune mice, which reacted specifically with dp72 in lysates of L. donovani, cross-reacted with one major band in total homogenates of Leishmania major and Leptomonas collosoma. Lymphocyte proliferation to crude and pure parasite Ag was also examined in mice immunized with dp72. Strong proliferation was found at low concentrations of crude L. donovani Ag (0.5 micrograms/ml) and with pure dp72. Proliferation at higher concentrations to crude L. major and L. collosoma Ag was observed. Little or no reaction (stimulation index < 1.0) was seen with other pure leishmanial Ag, including gp70-2, the promastigote surface protease, and lipophosphoglycan. Depletion in vitro of the CD4+ T cell subset from immune spleen cells abolished proliferation to dp72, whereas depletion of CD8+ T cells enhanced proliferation to the pure Ag. Experiments in vivo showed that immunized mice treated with antibodies to either CD4+, CD8+, both T cell subsets, or to IFN-gamma had larger LPB (178, 173, 176, and 130%, respectively) after challenge with L. donovani than nonimmunized controls. Mice immunized with dp72 but treated with either PBS or mouse Ig showed reduced LPB, 81 and 61%, respectively, compared with the nonimmunized animals. BALB/c mice immunized with dp72 were also protected against L. major which causes cutaneous leishmaniasis. Immunized mice infected with either 10(4) or 10(6) promastigotes did not develop lesions. Limiting dilution assays confirmed the protection. PMID- 8450216 TI - Mechanisms of experimental cancer cachexia. Local involvement of IL-1 in colon-26 tumor. AB - In the colon-26 (C-26) tumor model, the cytokine IL-6 is an important factor involved in experimental cancer cachexia. Recent in vitro data indicated that IL 1 plays a role in the interaction between host macrophages and C-26 cells that express IL-1R, resulting in the amplification of tumor IL-6 production. To investigate the role of IL-1 on the development of C-26 cachexia in vivo, the effect of specific blockade of the action of IL-1 with reagents against IL-1R was evaluated. Both IL-1R antagonist (IL-1RA) and the mAb 35F5 directed against IL-1R type I, prevented binding of radioactive IL-1, and inhibited IL-1-induced IL-6 synthesis by the C-26 cell line. Whereas a systemic administration of these reagents did not reverse weight loss in C-26-bearing mice, intratumoral injections of IL-1RA significantly reduced cachexia. Furthermore, body composition analysis confirmed that this treatment improved lean tissue and fat, as well as hypoglycemia and serum IL-6 level. The fact that the treatment did not change the tumor burden suggests that it affected the host directly. These results support the hypothesis that, at the microenvironment of the C-26 tumor, IL-1 is involved in the cachexia endured by the host. PMID- 8450217 TI - IFN-gamma modulation of epithelial barrier function. Time course, reversibility, and site of cytokine binding. AB - The single cell-thick intestinal epithelium forms a crucial barrier between the host and environment, and is modeled in vitro by a monolayer of polarized, highly differentiated T84 epithelial cells impermeable to most macromolecules because of functional intercellular tight junctions. Absence of a permeability defect across the monolayer, either transcellular or paracellular, is indicated by development of a transepithelial electrical resistance of > or = 1000 ohm-cm2, reported to be markedly diminished by exposure to a T lymphocyte cytokine, IFN-gamma. We sought to define this phenomenon in four ways by determining its duration and reversibility; the uniqueness of type II (gamma) IFN as opposed to type I (alpha) IFN; the surface of the polarized columnar epithelium likely involved in responding to IFN-gamma; and whether a specific surface membrane receptor on the epithelial cell participates in the response. Using a special apparatus that allows differential cytokine exposure of monolayer surfaces, our data demonstrate 1) only the monolayer's basolateral surface is IFN-gamma responsive, whereas the apical (microvillous) surface is no; 2) the alteration in electrical resistance of epithelium is prolonged (5 days), even after a single (24 h) exposure to IFN gamma, but nevertheless is reversible; 3) the effect is likely receptor-ligand mediated, because it can be partially blocked by IFN-gamma receptor-specific monoclonal Ig; 4) an alteration in tight junction function (a paracellular pathway) rather than cell necrosis or a transcellular pathway is responsible for IFN-gamma-induced monolayer dysfunction because permeability to a 44,000-Da macromolecule (horseradish peroxidase) did not increase, and intracytoplasmic T84 cell enzymes were not released into the media; and 5) the biologic phenomenon could not be induced by a species (alpha) of class I IFN, making IFN-gamma reasonably unique in this regard. Given the proximity; activation status, and capacity of T lymphocytes for cytokine production in mucosa, we suggest that IFN gamma-induced changes in epithelial permeability may be a major cause of altered intestinal barrier function in vivo. PMID- 8450219 TI - Culture of human monocytes with granulocyte-macrophage colony-stimulating factor results in enhancement of IFN-gamma receptors but suppression of IFN-gamma induced expression of the gene IP-10. AB - The initiation and promulgation of chronic inflammation are controlled in part by the various pro-inflammatory and anti-inflammatory cytokines present at the site of injury. IFN-gamma and granulocyte-macrophage CSF (GM-CSF) are two cytokines that can contribute to the inflammatory state and possess both pro- and anti inflammatory properties. However, the characterization of the interaction between GM-CSF-cultured monocytes and IFN-gamma is poorly documented. In this report we show that culture of human peripheral blood monocytes for up to 6 days in the presence of GM-CSF results in an eightfold increase in the level of IFN-gamma R expression, as determined by radioligand binding. The IFN-gamma R on these cells maintains a specificity typical of that observed in fresh monocytes. Only IFN gamma, not IFN-alpha or -beta, blocks the binding of IFN-gamma to its receptor, and anti-IFN-gamma R antibodies block at least 80% of binding of IFN-gamma to these cultured cells. However, in spite of increased receptor expression, GM-CSF cultured monocytes have a diminished response to IFN-gamma, as measured by the induction of the gene for IP-10 (a member of the platelet factor-4/IL-8 family). On the other hand, IFN-gamma-induced activation of the DNA-binding protein FcRF gamma is maintained in GM-CSF-cultured monocytes. Therefore, suppression of IFN gamma-mediated IP-10 induction is not the result of a global abrogation of signal transduction across the IFN-gamma R but a more selective inhibition that appears to occur downstream of the receptor. PMID- 8450218 TI - The oligomeric nature of the murine Fc epsilon RII/CD23. Implications for function. AB - The low affinity receptor for IgE (Fc epsilon RII/CD23) is a type II integral membrane protein with an extracellular C-terminal region homologous to C-type animal lectins. Immediately adjacent to this lectin homology region is a sequence that is predicted to form an alpha-helical coiled-coil stalk leading to dimer or trimer formation. This provides an explanation for the known self-associative capacity for the Fc epsilon RII. In this study the self-association to a trimer or tetramer is shown with rFc epsilon RII by chemical cross-linking and affinity purification on IgE columns. The data indicate that only the oligomeric form of Fc epsilon RII has sufficient affinity/avidity to bind to an IgE adsorbent. In contrast, Fc epsilon RII that is purified using anti-Fc epsilon RII mAb adsorbents has largely lost its capacity to bind IgE, as well as its capacity to self-associate, indicating that IgE recognizes the oligomeric form of the Fc epsilon RII. This phenomenon was further examined by performing detailed binding analysis of the mouse IgE/Fc epsilon RII interaction. A biphasic binding curve with high (2-7 x 10(7) M-1) and low (2-7 x 10(6) M-1) affinity binding was seen. Fc epsilon RII mutants were prepared that lack one or more of the 21 amino acid homologous repeat domains in the stalk region of the molecule. These mutant Fc epsilon RII molecules bound IgE with only a single low affinity (5-10 x 10(6) M 1). In addition, cross-linking analysis of one of these mutants demonstrated that it does not exhibit the receptor self-association seen for the intact Fc epsilon RII. Two chimeric Fc epsilon RII molecules were prepared having the mouse Fc epsilon RII lectin homology (carboxyl-terminal) region and the stalk region of either the related human Fc epsilon RII or the corresponding domain of Ly-49. Chimeric molecules using the former (alpha-helical coiled-coil) stalk supported normal binding of IgE although the Ly-49/Fc epsilon RII chimera failed to bind IgE. Taken together, the results indicate that high (approximately 10(8) M-1) affinity IgE binding results from interaction of multiple lectin domains with (presumably) symmetrical sites on the IgE molecule. Specificity for IgE is determined by the lectin domain although the binding avidity is determined by oligomerization through the coiled coil stalk. PMID- 8450220 TI - Lung surfactant suppresses oxygen-dependent bactericidal functions of human blood monocytes by inhibiting the assembly of the NADPH oxidase. AB - Surfactant is known to lower the surface tension in alveoli and affects the antibacterial functions of alveolar and peritoneal macrophages. We investigated the effects of surfactant on the bactericidal functions and oxidative metabolism of human blood monocytes and granulocytes. Monocytes incubated with surfactant ingest this material and subsequently exhibit an impaired ability to kill ingested bacteria. Granulocytes incubated with surfactant do not ingest this material, and their bactericidal functions are not affected. However, granulocytes that have ingested surfactant-coated Staphylococcus aureus display an impaired ability to kill these bacteria. Moreover, in monocytes and granulocytes that contain surfactant--the latter by ingestion of surfactant coated S. aureus--the intracellular production of H2O2 is impaired due to inhibition of the assembly of the NADPH oxidase. Together these results demonstrate that surfactant inside monocytes and granulocytes inhibits the capacity of these cells to kill bacteria intracellularly by impairing oxygen dependent killing mechanisms. PMID- 8450221 TI - Platelet-derived growth factor (PDGF) activates primitive hematopoietic precursors (pre-CFCmulti) by up-regulating IL-1 in PDGF receptor-expressing macrophages. AB - Platelet-derived growth factor (PDGF-BB) is known to stimulate growth of fibroblasts and smooth muscle cells via interaction with specific PDGF-B receptors on their surfaces. Hematopoietic precursor cells are not known to respond directly to PDGF, and PDGF receptors have never been reported on normal hematopoietic cells. We report a consistent stimulatory effect of PDGF-B on primitive pluripotential hematopoietic cells (pre-CFCmulti) in suspension cultures of mouse bone marrow that resembles effects obtainable previously only with IL-1. Further, we show that the effect depends on plastic-adherent accessory cells and is abrogated by neutralizing antibodies to IL-1 beta, that PDGF strongly up-regulates IL-1 mRNA levels in marrow macrophages but not in marrow fibroblast lines, and finally provide a first report of expression of RNA transcripts for PDGF-B receptors in normal marrow macrophages. Together, the results suggest the existence of a novel cytokine loop implicating monocyte/macrophages as cells reactive to PDGF and highlighting IL-1 induction as a significant feature of their PDGF response. PMID- 8450223 TI - Comparison of the requirements for cognate T cell help for IgG anti-double stranded DNA antibody production in vitro: T helper-derived lymphokines replace T cell cloned lines for B cells from NZB.H-2bm12 but not B6.H-2bm12 mice. AB - We have isolated, from NZB.H-2bm12 mice, several autoreactive cloned T cell lines that provide help for anti-dsDNA IgG antibody production in vitro. The purpose of the work described herein was to examine the requirement for cognate help for the production of anti-DNA antibodies in vitro. Thus, the ability of cloned T cell lines or lymphokines derived from them to provide help for T-depleted spleen cells from both normal B6.H-2bm12 mice and SLE-prone NZB.H-2bm12 mice was examined. Two autoreactive cloned T cell lines were selected for detailed study. 410F T cells respond to APC from both I-Ab and I-Abm12 mice, whereas 410H T cells are restricted to I-Abm12. By using Percoll gradients, B cells from both low density and high density fractions were cultured with autoreactive cloned T cell lines or lymphokines secreted by such cloned T cell lines, and anti-DNA antibody production was determined. Lymphokines elicited IgM anti-ssDNA antibody production from cells in all Percoll fractions from both B6.H-2bm12 and NZB.H 2bm12 mice. Lymphokines did not elicit production of IgG anti-dsDNA antibody production by cells from 2-month-old B6.H-2bm12 mice. In contrast, substantial production of IgG anti-dsDNA antibody was observed for NZB.H-2bm12 cells in response to lymphokines alone. Thus, B cells from NZB.H-2bm12 mice, because of previous activation in vivo, can proceed to IgG anti-dsDNA antibody production in vitro without direct T cell interaction. When we examined direct T cell help for the IgG anti-dsDNA antibody response, we found that we could distinguish the actions of the two cloned T cell lines studied. 410F T cells provided help predominantly for cells from low density Percoll fractions whether the cells were derived from B6.H-2bm12 or NZB.H-2bm12 mice. 410H T cells were capable of providing help for cells from both the low and high density fractions, and this help accounted for more than half of the antibody production in vitro by cells from B6.H-2bm12 mice. PMID- 8450222 TI - Stimulation of human T cells by streptococcal "superantigen" erythrogenic toxins (scarlet fever toxins). AB - The pyrogenic (erythrogenic) exotoxins A and C (SPEA and SPEC) of Streptococcus pyogenes belong to the family of mitogenic toxins of which the staphylococcal enterotoxins are the prototypes. The erythrogenic toxin B (SPEB) is a proteinase precursor. All SPE have been reported to be superantigens. Here we have analyzed the human T cell response to these toxins. We used highly purified preparations of SPEA, SPEB, and SPEC from different S. pyogenes strains. These toxins were apparently homogenous in SDS-PAGE, IEF, and HPLC. In addition, recombinant SPEA and SPEC were produced in Escherichia coli. In cultures of PBMC, all three toxins expanded preferentially a fraction of T cells. Using mAb against V beta 2, -5, 6, -8, and -12, we investigated the phenotype of the stimulated cells. Natural SPEA, SPEB, and SPEC strongly stimulated V beta 8+ T cells, whereas recombinant SPEA and SPEC did not. Both natural and recombinant SPEA stimulated V beta 12+ cells and both natural and recombinant SPEC stimulated V beta 2+ cells. In accordance with these findings, a human V beta 8+ line responded to all three toxins derived from S. pyogenes but not to the recombinant proteins. An antiserum against natural SPEC neutralized specifically the V beta 2-stimulating activity of SPEC and the V beta 8-stimulating activity of all three toxins, but had no effect on the response to other superantigens. This shows that trace amounts of a potent novel V beta 8-stimulating activity not identical to SPEA and SPEC are responsible for the stimulation of V beta 8+ T cells by natural SPEA and SPEC reported previously. In a preliminary screening of S. pyogenes strains from patients, we found that this novel superantigen appears to be more widely distributed than SPEA and SPEC. Furthermore, we present evidence that also the superantigenic properties of SPEB are due to contaminations with this V beta 8 stimulator. The response to SPEB usually required 1000 times higher concentrations than to SPEA or SPEC. Antisera to SPEC but not to SPEB inhibited the response of PBMC and V beta 8+ Jurkat cells to SPEB. Furthermore, more stringent purification of SPEB yielded SPEB preparations devoid of mitogenic activity. These results indicate that the mitogenicity that is commonly attributed to SPEB is due to minute contaminations of the V beta 8 stimulator. These results raise two important caveats for the work with these highly potent T cell mitogens.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8450224 TI - HIV-gp 160-induced T cell-dependent B cell differentiation. Role of T cell-B cell activation molecule and IL-6. AB - The HIV envelope glycoprotein gp160 has been previously demonstrated to induce differentiation of normal B lymphocytes into Ig-secreting cells; the response is T cell-dependent, and T cells pretreated with gp160 can support B cell differentiation. This study investigates the cell surface molecules and cytokines that play a role in the gp160-induced T-B cell interaction. Utilizing CD4+CD45RO+ cloned T cells as the source of helper cells, we observed that physical contact with B cells is essential for the gp160-induced B cell response; no IgG-secretion occurred if T cells were separated from the B cells by culturing them in Transwell chambers. The expression of T cell-B cell activation molecule, a novel surface molecule associated with T cell activation, was moderately increased by gp160, and antibody to T cell-B cell activation molecule abrogated the gp160 mediated Th cell function. Cell surface molecules LFA-1, ICAM-1, HLA-DR, CD28, and B7 were also involved in the T-B cell interaction since mAb to any of these molecules inhibited the gp160-induced B cell differentiation response. gp160 also induced IL-6R and CD23 molecule expression on B cells when added to cultures of T plus B cells; there was CD23 expression only in cells that formed conjugates with T cells. Paraforamaldehyde-fixed, gp160-pretreated T cells failed to elicit IgG responses in B cells, but did induce CD23 and IL-6R up-regulation on B cells. Addition of exogenous IL-6, but not IL-2 or IL-4, restored the IgG secretion. These findings indicate that the T cell dependence for gp160-induced B cell differentiation responses involves two steps: one requires contact-dependent interaction of several cell surface molecules, and the second requires IL-6 secretion. PMID- 8450225 TI - Autoimmunity to cytoskeletal protein tropomyosin. A clue to the pathogenetic mechanism for ulcerative colitis. AB - Autoimmunity has been emphasized in the pathogenesis of ulcerative colitis and various anticolon antibodies have been described. Nevertheless, the nature of the autoantigens has been elusive. Using ulcerative colitis colon-eluted IgG antibody, we earlier detected an M(r) 40,000 protein, P40, in colon extract. In our study, we purified P40 from human colon to apparent homogeneity, sequenced two peptides after proteolytic digestion, and demonstrated that the P40 belongs to the tropomyosin family. Furthermore, we demonstrated that blood serum from 95% of patients with ulcerative colitis contains antibodies that are reactive to tropomyosin. PMID- 8450226 TI - The bimodal expression of tumor necrosis factor-alpha in association with rat lung reimplantation and allograft rejection. AB - Lung transplantation has become a therapeutic option for a number of end-stage pulmonary disorders. Lung transplant recipients experience more complications due to acute and chronic allograft rejection as compared to recipients of other solid organs. We postulated that the generation of TNF-alpha plays a significant role in the pathogenesis of acute lung allograft rejection. To test our hypothesis, we used a RT1-incompatible rat lung allograft model and demonstrated the time course, cellular source(s), and major compartment(s) of TNF production during the course of lung allograft rejection. This model allowed for immunogenetic standardization and reproducibility of lung allograft rejection across disparate major histocompatibility barriers. TNF production was characterized at the whole animal, organ, cellular, and molecular levels, and was found to be compartmentalized and expressed in a bimodal fashion from the lung allograft during lung allograft reimplantation and maximal rejection. Lung allograft rejection was significantly attenuated in animals pretreated with neutralizing TNF antisera as compared to animals receiving control sera. These findings may provide interesting insight into the use of novel and specific therapeutic intervention(s) during periods of acute lung allograft rejection. PMID- 8450227 TI - Involvement of IFN-gamma and transforming growth factor-beta in graft-vs-host reaction-associated immunosuppression. AB - The mechanisms of the suppressive activity of spleen cells from mice undergoing a graft-vs-host reaction (GVH) to non-H-2 histocompatibility Ag were investigated. In our model GVH is induced by injecting bone marrow and spleen cells from B10.D2 (H-2d Mlsb) donors into lethally irradiated (DBA/2 x B10.D2)F1 (H-2d/d Mlsa/b) recipients that differ only with regard to non-H-2 Ag. GVH spleen cells inhibit the mitogenic responses to Con A and LPS, as well as the anti-bromelain-treated mouse RBC (Br-MRBC) antibody response. This suppression was nonspecific and non-H 2-restricted and was not modified after treatment with anti-Thy-1 plus C. Conversely it was abrogated after treatment with L-leucyl methyl ester. These features permitted the identification of non-T cell, L-leucyl methyl ester sensitive, cells involved in this type of suppression. The suppression mediated by GVH spleen cells was linked to the activity of IFN-gamma and transforming growth factor-beta 1 (TGF-beta 1) (TGF-beta 1 was found to be synthesized by GVH spleen T cells). mAb to IFN-gamma abrogated the suppression of the mitogenic response to Con A and the anti-Br-MRBC response and slightly reversed the suppression of the mitogenic response to LPS. Anti-TGF-beta 1 antibody partially abrogated the suppression of the mitogenic response to LPS and totally abrogated that of the anti-Br-MRBC response but left unmodified the suppression of the mitogenic response to Con A. These results are discussed within the framework of the mechanisms underlying the immunosuppression associated with GVH. PMID- 8450228 TI - Expression of CSF-1, c-fms, and MCP-1 in the central nervous system of rats with experimental allergic encephalomyelitis. AB - We have examined the expression of factors associated with the growth, differentiation, and chemotaxis of cells of the monocyte/macrophage series in the central nervous system of Lewis rats sensitized to develop experimental allergic encephalomyelitis. CSF-1 mRNA increased significantly over that found in control animals (sensitized with OVA in CFA or CFA alone). The elevation in the levels of this growth factor commenced immediately before the onset of early clinical signs and peaked immediately before maximal clinical incidence of disease. Expression of CSF-1 message declined to base-line values with resolution of the disease process. CSF-1 protein was also detected in the central nervous system at the height of clinical disease. Expression of the receptor for CSF-1, the proto oncogene c-fms, also paralleled the early disease process. Elevated levels of c fms mRNA were detected immediately before the onset and peaked at the height of clinical signs of disease. In contrast to CSF-1 levels, elevated c-fms message expression persisted after resolution of the acute phase of experimental allergic encephalomyelitis. Levels of macrophage chemotactic factor-1 message were also elevated immediately before the onset of clinical signs, peaked with the height of clinical disease, and declined with resolution of the disease. Unlike CSF-1 or c-fms, no endogenous macrophage chemotactic factor-1 message was detected in control animals. Macrophage chemotactic factor-1 protein was demonstrated by Western blot in the central nervous system at the height of clinical disease. The results support the conclusion that expression of factors that specifically target cells of the monocyte/macrophage series are an important component of the disease process in experimental allergic encephalomyelitis. PMID- 8450229 TI - Defects in the differentiation and function of antigen presenting cells in NOD/Lt mice. AB - Although T lymphocytes are the ultimate effectors of pancreatic beta cell destruction in autoimmune insulin-dependent diabetes, previous work has established that beta cell autoreactive T cells are generated in nonobese diabetic (NOD) mice as a result of APC dysfunctions. To determine if APC dysfunctions could result from developmental defects, we analyzed if macrophages (M phi) develop normally from NOD bone marrow stimulated with CSF-1 in the presence and absence of IFN-gamma. Due to interactions between the diabetogenic H 2g7 haplotype and background modifiers, NOD bone marrow cells were found to proliferate poorly to CSF-1 stimulation. IFN-gamma aberrantly increased CSF-1 stimulated proliferation of H-2g7 expressing bone marrow cells, although decreasing proliferation of bone marrow cells expressing diabetes resistant MHC haplotypes. FACS analysis indicated the diminished sensitivity of NOD hematopoietic precursors to CSF-1 was associated with a quantitative inability to generate phenotypically mature M phi. In addition to developmental defects, NOD M phi were also found to be functionally defective. Total MHC class I expression was aberrantly down-regulated in a tissue specific fashion in IFN-gamma-treated M phi from NOD mice, whereas MHC class I expression increased as expected in M phi from C57BL/KsJ (BKs) control mice. Total MHC class I expression also increased in IFN-gamma-treated M phi from NOR mice, a diabetes-resistant control strain that shares the H-2g7 haplotype of NOD, but contains BKs-derived genomic elements on chromosomes 2, 4, 11, and 12. This demonstrates differential trans-regulation of class I loci within the diabetogenic H-2g7 haplotype in NOD vs diabetes-resistant NOR mice. Aberrant down-regulation of MHC class I content in IFN-gamma-treated M phi from NOD mice was associated with decreased ability to activate CTL function. We propose these defects in M phi differentiation and function may interact with H-2g7 to generate APC in NOD mice that are unable to activate tolerogenic mechanisms, but remain capable of activating low level effector responses. PMID- 8450230 TI - Accessory cell function of human eosinophils. HLA-DR-dependent, MHC-restricted antigen-presentation and IL-1 alpha expression. AB - Although peripheral blood eosinophils express little of the class II MHC protein, HLA-DR, eosinophils could be induced to express HLA-DR by exposures to cytokines, including granulocyte-macrophage-CSF, IL-4, and IFN-gamma, with granulocyte macrophage-CSF eliciting the greatest level of HLA-DR expression as assessed by flow cytometry. The capacity of HLA-DR+ eosinophils to function as APC was evaluated with blood eosinophils isolated free of mononuclear cells, cultured with granulocyte-macrophage-CSF to induce HLA-DR expression and then exposed to the Ag tetanus toxoid. HLA-DR+ eosinophils fixed with paraformaldehyde after Ag exposure stimulated T cell proliferation, whereas HLA-DR+ eosinophils fixed with paraformaldehyde before Ag exposure failed to stimulate lymphocyte proliferation. The lymphocyte proliferative responses elicited by Ag-pulsed HLA-DR+ eosinophils were inhibited by anti-HLA-DR mAb and were restricted to HLA-DR compatible lymphocytes. Moreover, eosinophils from a hypereosinophilic donor, both before and more prominently after stimulation with PMA, contained transcripts for IL-1 alpha mRNA detectable by Northern blot hybridization and in situ hybridization and expressed IL-1-alpha protein detectable by immunohistochemistry. These findings indicate that human eosinophils can process Ag, express the costimulatory cytokine IL-1-alpha, and after cytokine-elicited induction of HLA DR expression can function as HLA-DR-dependent, MHC-restricted APC in stimulating T lymphocyte responses. PMID- 8450232 TI - Determination of antibody affinity by ELISA with a non-linear regression program. Evaluation of linearized approximations. AB - ELISA experiments based on competition between immobilized and soluble antibody for soluble antigen, and on the formation of a ternary complex of immobilized antibody, antigen and soluble antibody were used by Hoylaerts et al. (J. Immunol. Methods 126 (1990) 253-261) for the determination of dissociation constants. The dissociation constant was taken from linearized plots according to a theory that required several approximations. The effect of these approximations on the resulting dissociation constants has been investigated using two computer programs, CBEIA-C and CBEIA-S. Since most approximations that have to be made for linearization can be avoided by non-linear regression, the programs provide a more reliable basis for calculation of the dissociation constant. Experiments measuring formation of a ternary complex were found to be unsuitable for affinity determination. PMID- 8450231 TI - An efficient procedure for the generation of human monoclonal antibodies based on activation of human B lymphocytes by a murine thymoma cell line. AB - A new, efficient procedure for the generation of human monoclonal antibodies has been developed. The procedure is based on the activation of human B cells in microwells by murine thymoma EL4B5 cells. This mode of B cell stimulation leads to proliferation of at least one per eight of human B cells and to a high rate of antibody production. Subsequently, supernatants of the microwells are screened by ELISA for the presence of antibody of the desired specificity and B cells from selected wells are hybridized by electroporation. To optimize the procedure, the kinetics of the B cell expansion induced by EL4B5 cells were analysed. Counting and phenotyping of cultured cells at different time points indicated that the peak of B cell expansion occurred at day 5 for tonsil B cells (16-fold increase) and at day 7 for peripheral blood B cells (20-fold increase). The B cells did not merely proliferate but also differentiated, as indicated by loss of CD20 expression and increase of CD38 expression. At the peak of B cell expansion, B cells could be hybridized efficiently with myeloma cells. The majority of the resultant hybridomas secreted human immunoglobulin. The efficiency of the procedure is exemplified by the generation of hybridomas secreting human IgG against Haemophilus influenzae from limited numbers of either human tonsil B lymphocytes or peripheral blood B lymphocytes. PMID- 8450233 TI - Use of stable 6-aminohexyl derivatives for labelling polysaccharides with haptens and for preparing polysaccharide immunoadsorbents. PMID- 8450234 TI - A safe and rapid method for analyzing apoptosis-induced fragmentation of DNA extracted from tissues or cultured cells. PMID- 8450235 TI - CBEIA: programs for simulation of ELISA experiments and affinity determination. AB - Two computer programs for the analysis of results of enzyme immunoassays are presented. CBEIA-C simulates ELISA experiments based on competition between immobilized and soluble antibody for a soluble antigen (or vice versa). CBEIA-S simulates the formation of a ternary complex of immobilized antibody, antigen and soluble antibody. The programs provide a more reliable basis for affinity determination than linearized plots. Results obtained by the application of these programs are described in the accompanying paper on pp. 129-133). PMID- 8450237 TI - Fluorescent europium chelates as target cell markers in the assessment of natural killer cell cytotoxicity. AB - A time-resolved fluorometric assay for the detection of natural killer cell activity against target cells labelled with the fluorescent chelate europium-6,6" bis[N,N-bis(carboxymethyl)-aminomethyl]-4'-phenyl-2,2',6', 2"-terpyridine (EuCAPT) has been developed. In the assay released EuCAPT from lysed K-562 cells is measured in the supernatant after co-incubation of the target cells with effector cells. Thus, the performance of the assay is essentially similar to the previously described EuDTPA assay and the widely used 51Cr assay. EuCAPT is released from target cells lysed by effector cells faster than 51CrO4(2-) but somewhat slower than EuDTPA. In contrast to methods based on prompt fluorometry the autofluorescence from culture medium supplemented with serum can be avoided by the use of time-resolved fluorometry. The result shows that fluorescent europium chelates provide an alternative to radioactive markers currently used for the assessment of in vitro cellular cytotoxicity. PMID- 8450236 TI - Generation of human monoclonal antibodies by transformation of lymphoblastoid B cells with ras oncogene. AB - Human monoclonal antibodies (hu-mAbs) of predetermined specificity and isotype are potentially important for a variety of applications, including therapy and diagnosis. Their efficient generation, however, is still hampered by technical difficulties. Even the most established approaches to the generation of hu-mAbs, i.e., B cell immortalization by Epstein-Barr virus (EBV) and/or fusion with appropriate myeloma cell lines, are characterized by a relatively low efficiency. It has been shown that expression of activated Ha- or N-ras oncogenes causes the malignant transformation and plasmacytoid differentiation of EBV-immortalized lymphoblastoid cell (LC) lines, suggesting that activated ras oncogenes can convert LC lines into effective hu-mAb producers. We have used retroviral vector mediated gene transfer to introduce an activated Ha-ras (v-ras) oncogene into four distinct LC lines producing hu-mAbs of different classes (IgM and IgG) and specificities (to human insulin, human thyroglobulin and rabies virus glycoprotein). The cloning efficiency and antibody secretion of these ras transformed LC (ras-LC) lines were compared with those of the hybrid LC (hyb-LC) lines generated by fusing the same parental LC lines with the Ig non-secretor F3B6 human-mouse hybrid cells. ras-LC lines were comparable to their hybrid counterparts in either parameter tested. This, together with the relatively higher efficiency of the method, suggests that ras transformation may constitute a valid alternative to the currently available technologies for hu-mAbs production from LC lines. PMID- 8450238 TI - Selective biotinylation of Neisseria meningitidis group B capsular polysaccharide and application in an improved ELISA for the detection of specific antibodies. AB - A method is described for the selective biotinylation of meningococcal capsular polysaccharide from Neisseria meningitidis group B and its application to an enzyme-linked immunoabsorbent assay (ELISA) to detect specific antibodies by immobilization on streptavidin-coated microtiter wells. Capsular polysaccharide from Neisseria meningitidis B has been biotinylated by specific periodate oxidation of terminal residues and condensation of the resulting aldehydes with biotin hydrazide, using a spin-column technique in the intermediate purification steps. The ELISA was optimized employing an extended reaction time between the label alkaline phosphatase and its most common substrate, p-nitrophenyl phosphate, together with evaluation of blocking agents to minimize non-specific binding. Specificity was demonstrated by a direct competitive enzyme immunoassay (EIA). PMID- 8450240 TI - A new approach for measurement of cytotoxicity using colorimetric assay. AB - Using in vitro established tumour cell lines attempts were made to assess the suitability of tetrazolium salt reduction (MTT) assay to replace the conventional radioactive base techniques for measuring cell proliferation and cell killing. The optimum conditions for MTT loading time, concentration of MTT and the time for colour development were found to be 4 h, 5 mg/ml and 30 min respectively, conditions which were used for subsequent experiments. Analysis of the correlation between increasing cell numbers and optical densities (OD) showed a direct relationship with correlation of coefficient values of r > 0.98 and 10,000 cells/well was found to provide an accurate ODs for a wide variety of cell types. The accuracy of replicate readings of the assay was investigated by setting a wide range of cell numbers and the variation among seven replicates was calculated and found to be less that 6% of the mean values. The reproducibility of the assay for two cell lines was tested using the lines on four different occasions. The ODs for Jar and Fen cell lines were 0.80 +/- 0.01, 0.82 +/- 0.02, 0.90 +/- 0.02, 0.79 +/- 0.05 and 0.56 +/- 0.01, 0.58 +/- 0.03, 0.60 +/- 0.02 and 0.61 +/- 0.02 respectively giving maximum variation of less than 11% of mean on repeated testings. Comparison between the results of MTT with 3H-Tdr or 51Cr release assays showed a high degree of correlation over a wide range of cell numbers and cell types. The r values between the results of MTT with 3H-Tdr (for cell number ranging from 1.8 to 60 x 10(3)/well) or 51Cr release assays (for E/T ratios of between 5:1 and 40:1) were 0.89 (p = 0.001) and 0.96 (p < 0.03) respectively. These results demonstrate that it is possible to use the MTT assay interchangeably with radioactive base techniques to measure cell proliferation and cytotoxicity. The ease of its execution, safety and its suitability for analysing as few as 3000 cells makes this method a serious contender for replacing the conventional radioactive techniques. PMID- 8450239 TI - A sensitive method to detect defined peptide among those eluted from murine MHC class II molecules. AB - We developed a sensitive competitive inhibition radioimmunoassay able to trace pmoles of a defined peptide eluted from major histocompatibility complex (MHC) class II molecules that were subsequently fractionated by RP-HPLC. In this assay we used a model synthetic peptide corresponding to amino acid residues 110-120 from the hemagglutinin (HA) of PR8 influenza virus, and affinity purified rabbit antibodies specific for this peptide. The HA110-120 peptide binds to I-Ed class II molecules on the surface of APCs and is recognized by specific CD4+ T helper cells. 2PK3 B lymphoma cells (H-2d) were pulsed with HA110-120 peptide or PR8 virus, lysed, the MHC class II molecules extracted, and bound peptides eluted. After separation by RP-HPLC, the fractions were tested for inhibition of the binding of rabbit anti-HA110-120 antibodies to peptide coated microtiter plates. A significant inhibitory activity was observed with one peak when the cells were pulsed with HA110-120 peptide and two peaks when pulsed with PR8 virus. The inhibitory activity was correlated with the presence of HA110-120 peptide as demonstrated by peptide sequencing. The assay is reproducible and sensitive to 1 pmol of antigenic peptide. This assay can be useful to identify microbial peptides with defined structure and antigenicity among the multiple peptides bound to class II molecules. PMID- 8450241 TI - Assessment of the suitability of commercially available SpA affinity solid phases for the purification of murine monoclonal antibodies at process scale. AB - Eight commercially available staphylococcal protein A (SpA) affinity chromatography solid phases were evaluated in order to establish their potential for the large-scale purification of a murine monoclonal antibody (MAb, mIgG1). The antibody was produced in-house, serum-free, in a hollow fibre bioreactor. Solid phases were tested for the effects of salt concentration, pH, and the presence of MAb on ligand leakage and flow rate. These effects were compared using the solid phases in stirred-tank (roller-mixing) and flow-through (packed bed) modes of operation. Ligand leakage in the absence of MAb was generally at its lowest when the solid phases were used in a flow-through mode. In this mode of operation increasing the inorganic salt concentration and pH of the washing/adsorption buffer from 150 mM at pH 8.6, to 3 M at pH 8.9, typically produced a 10% increase in MAb capacity of the solid phases (20% for Sepharose CL 4B). However, contamination of the purified antibodies was also greatly increased due to an elevated level of background ligand leakage from the matrices. Residual contaminating levels of SpA in affinity purified MAbs were lowest with a low salt (NaCl, 150 mM) glycine (1 M) adsorption/washing buffer. Maximal antibody capacity was achieved for all matrices on frontal analysis (breakthrough curves), as opposed to a pulse mode of use. The largest capacity was found for Prosep A 'high capacity' (12-15 mg/ml column volume), where capacity approached its experimentally determined theoretical capacity (C/Co = 0.5) regardless of its mode of use. The relatively high MAb capacity of Prosep A 'high capacity' was further reflected in a superior dynamic isotherm. Frontal analysis, however, generally resulted in a greater SpA contamination of the purified MAbs. Under these conditions the lowest levels of SpA contamination were found for the Prosep A 'high capacity', and Repligen solid phases (12 ppm) on purifying 12.8 and 4.3 mg of MAb respectively. For the large scale downstream processing of a MAb for therapeutic applications, Prosep A 'high capacity', would appear to be the most appropriate of the solid phases tested. PMID- 8450242 TI - Alcohol intake increases human immunodeficiency virus type 1 replication in human peripheral blood mononuclear cells. AB - The effects of alcohol consumption on various T lymphocyte subset functions and on the degree of susceptibility of peripheral blood mononuclear cells (PBMC) to human immunodeficiency virus (HIV) type 1 infection and replication in vitro were investigated. PBMC from 60 HIV-1-seronegative healthy volunteers were studied before and after ingestion of alcohol beverages. After alcohol consumption, there was significantly increased HIV-1 replication (P < .001) in PBMC, as determined by HIV-1 p24 antigen levels in the culture supernatants, than in cultures obtained before alcohol ingestion. There was a decreased ability of lymphocytes, obtained after alcohol consumption, to produce interleukin-2 and soluble immune response suppressor activity after stimulation with concanavalin A. The data show that alcohol ingestion increases HIV-1 replication in human PBMC infected with HIV-1 in cell culture. This may be due to alcohol-induced functional impairment of various subsets of lymphocytes in the peripheral blood. Thus, HIV-1 replication may be augmented by alcohol in HIV-1-infected individuals, and alcohol intake may increase an individual's risk for acquiring HIV-1 infection. PMID- 8450243 TI - Detection of human immunodeficiency virus type 1 in semen: effects of disease stage and nucleoside therapy. AB - The effects of clinical stage of infection and antiviral therapy on the detection of human immunodeficiency virus type 1 (HIV-1) nucleic acids in semen were investigated by the polymerase chain reaction. HIV-1 was detected in 45 (87%) of 52 semen specimens from 29 (81%) of 36 men. Seventeen (77%) of 22 stage II or III subjects and 12 (86%) of 14 stage IV subjects had positive specimens. The CD4+ lymphocyte count was not significantly different comparing subjects with positive and negative semen. Moreover, 6 (67%) of 9 untreated men had positive specimens compared with 23 (85%) of 27 men treated with zidovudine, 2',3'-dideoxyinosine, or both for a mean of 20 months. Thus, the detection of HIV-1 in semen was independent of both stage of infection and long-term treatment. In a semiquantitative analysis of 6 men followed for 8 weeks after the start of nucleoside therapy, a decrease in HIV-1 RNA in seminal plasma was demonstrated in 2. PMID- 8450244 TI - Patients infected with human immunodeficiency virus type 1 have low levels of virus in saliva even in the presence of periodontal disease. AB - In two consecutive studies, 80 subjects human immunodeficiency virus (HIV)-1 seropositive (21 asymptomatic, 6 persistent generalized lymphadenopathy, 13 AIDS related complex, and 40 AIDS) were examined for oral lesions. Paired serum and saliva specimens were tested for HIV isolation, DNA, and antigen. HIV antigen was detected in sera from 31 patients, but not in saliva. HIV was isolated from blood mononuclear cells of 83% and saliva supernatants of 21%. In the second study of 25 patients, HIV was detected in plasma of 56% (titers, 1/10 to > 1/1000) but not in diluted saliva supernatants, even in those with severe periodontal disease. HIV DNA was detected using polymerase chain reaction in 2 of 7 saliva cell pellets and 4 of 5 blood samples. Hence, infectious HIV and DNA was found at very low concentrations in 21% and 28% of HIV-seropositive patients, respectively, at all stages of HIV infection. PMID- 8450245 TI - Down-regulation of human immunodeficiency virus type (HIV-1) production after stimulation of monocyte-derived macrophages infected with HIV-1. AB - Macrophages infected with human immunodeficiency virus (HIV) can be stimulated as a result of secondary infections. The effect of stimulation of HIV-1-infected monocyte-derived macrophages on HIV-1 production by these cells was studied. Exposure of macrophages to phorbol 12-myristate 13-acetate or to opsonized Escherichia coli, Staphylococcus aureus, or zymosan resulted in a decrease in HIV production. HIV production was inversely related to the degree of stimulation, measured as lucigenin-enhanced chemoluminescence. The production of reactive oxygen intermediates, however, did not seem to be the direct cause of the diminished HIV production, since oxygen-radical scavengers did not prevent the decrease in HIV production. Furthermore, oxygen-radical scavengers did not affect HIV production by nonstimulated macrophages. These results indicate that activation signals have an opposite effect and reactive oxygen intermediates have no effect on HIV production in macrophages compared with the effect described in T cells. PMID- 8450246 TI - Study of human immunodeficiency virus resistance to 2'-3'-dideoxyinosine and zidovudine in sequential isolates from pediatric patients on long-term therapy. AB - Resistance to zidovudine (3'-azido-3'-deoxythymidine) and 2',3'-dideoxyinosine (ddI) has been reported for human immunodeficiency virus (HIV) isolates from adults, but little is known about these drugs in children. A new micrococulture assay was developed for evaluation of drug susceptibility using single-passage HIV isolates cocultured with peripheral blood mononuclear cells from healthy donors. HIV isolates from children treated with zidovudine or ddI were evaluated to define the emergence of resistance to these antiretroviral agents. Four patients were treated with ddI and 3 with zidovudine for > 15 months. There was a > or = 20-fold decrease in susceptibility to ddI for sequential isolates of HIV recovered from 4 patients treated with ddI for 22-31 months and a 4- to 10-fold decrease in susceptibility to zidovudine in 3 patients. HIV isolates from 3 patients treated with ddI or zidovudine alone showed a minor amount of cross resistance to the other antiretroviral agent. Results indicate the importance of monitoring antiretroviral drug susceptibility of HIV isolates when assessing clinical deterioration in children treated for > 1 year. PMID- 8450247 TI - Randomized placebo-controlled double-blind combined therapy with laser surgery and systemic interferon-alpha 2a in the treatment of anogenital condylomata acuminatum. The Condylomata International Collaborative Study Group. AB - An earlier study by this group failed to demonstrate significant therapeutic effect of 4 weeks of systemic recombinant interferon (IFN)-alpha 2 monotherapy on anogenital condylomata acuminatum. The present study was undertaken to determine if 3 MIU of IFN given three times weekly for 4 consecutive weeks and starting immediately after CO2 laser ablation of all visible warts would be effective. In a multicenter placebo-controlled randomized double-blinded study of 130 evaluatable patients followed for 36 weeks after treatment, no beneficial effects were noted in terms of complete response (24 placebo vs. 23 IFN patients) and recurrences (38 placebo vs. 46 IFN patients). None of the pretreatment and demographic characteristics affected outcome with statistically significant differences. CO2 laser ablation combined with systemic recombinant IFN-alpha 2 was ineffective in this study as treatment of anogenital condylomata. PMID- 8450248 TI - Reversal of the immunosenescent phenotype by dehydroepiandrosterone: hormone treatment provides an adjuvant effect on the immunization of aged mice with recombinant hepatitis B surface antigen. AB - This study sought to establish whether administration of dehydroepiandrosterone (DHEA) or its sulfate derivative to aged mice could effectively correct the immunosenescent phenotype. Supplemental DHEA sulfate and topical DHEA fully corrected the age-associated dysregulated production of T cell lymphokines by cells from all of the different lymphoid organs tested. Either DHEA or DHEA sulfate supplementation promoted enhanced antibody responses against recombinant hepatitis B surface antigen (rHBsAg) by the aged recipients when incorporated directly into the vaccine. When DHEA was provided either topically or was incorporated directly into vaccine, vigorous primary and secondary antibody responses were detected in the aged mice given a single administration of DHEA, regardless of the mode of administration. It was also established that DHEA treatment could enhance specific antibody responses to rHBsAg in aged animals that had previously not been effectively immunized by conventional vaccination procedures. PMID- 8450249 TI - Demonstration of Chlamydia pneumoniae in atherosclerotic lesions of coronary arteries. AB - Chlamydia pneumoniae is a human respiratory pathogen that causes acute respiratory disease and approximately 10% of community-acquired pneumonia. The infections are geographically widespread. Antibody prevalence studies have shown that virtually everyone is infected with the C. pneumoniae organisms at some time and that reinfection is common. In addition to respiratory disease, seroepidemiologic studies have shown an association of this organism with coronary artery disease. C. pneumoniae was detected in coronary artery atheromas by immunocytochemistry (15/36) and by polymerase chain reaction (PCR) (13/30) in 20 of 36 autopsy cases from Johannesburg, South Africa. Sequence analysis of the C. pneumoniae rRNA genes amplified by PCR confirmed that the amplified gene products were C. pneumoniae. Electron microscopy revealed typical pear-shaped C. pneumoniae elementary bodies in 6 of 21 atheromatous plaques. These findings support the seroepidemiologic studies and offer further evidence that C. pneumoniae may be involved in the atherosclerotic process. PMID- 8450250 TI - Penicillin-resistant Streptococcus pneumoniae strains recovered in Houston: identification and molecular characterization of multiple clones. AB - A sample of 48 penicillin-resistant Streptococcus pneumoniae (PRSP) strains recovered between January 1989 and May 1991, primarily from infected children in Houston, was characterized by multilocus enzyme electrophoresis and repetitive extragenic palindromic-polymerase chain reaction genomic profiling. A heterogeneous array of 22 clonal genotypes was identified, but 64% of the PRSP strains in the sample were assigned to five clones that are closely similar in overall chromosomal character and express serotype 6 capsule. A close genetic association between these five clones and penicillin-resistant 6B clones recovered in Alaska, Iceland, and Spain was identified by multilocus enzyme electrophoresis. Taken together, the results suggest either that the common resistant 6B clones in Alaska, Iceland, Spain, and Houston have a recent ancestor or that isolates of a certain pneumococcal phylogenetic lineage are more likely to develop penicillin resistance. PMID- 8450251 TI - Transferrin, iron, and serum lipids enhance or inhibit Mycobacterium avium replication in human macrophages. AB - Mycobacterium avium grows exponentially over 7 days in human macrophages when they are cultured in serumless medium. Normal serum inhibits this replication. When serum lipids were extracted using chloroform, the inhibitor was present in the lipid-free component. The lipid extract significantly enhanced M. avium replication. Iron (Fe2+) added at 8-80 micrograms/mL to infected macrophage cultures in serum resulted in enhanced mycobacterial replication. Serum-induced inhibition of bacterial growth in serumless medium could be duplicated with apotransferrin at 50-500 micrograms/mL. At 1000 micrograms/mL, apotransferrin no longer inhibited bacterial growth. Holotransferrin was not inhibitory, and at 500 micrograms/mL, it enhanced M. avium growth. Depletion of the transferrin in serum by affinity chromatography using goat anti-transferrin on protein G-Sepharose removed inhibitory activity. These results indicate that transferrin levels, transferrin saturation, iron levels, and serum lipids can profoundly alter the replication of M. avium in association with macrophages. PMID- 8450252 TI - Human anti-endotoxin antibody HA-1A mediates complement-dependent binding of Escherichia coli J5 lipopolysaccharide to complement receptor type 1 of human erythrocytes and neutrophils. AB - HA-1A has been shown clinically to decrease mortality in septic patients with gram-negative bacteremia. In this study, the ability of HA-1A to augment the serum complement-dependent immune adherence of 125I-labeled Escherichia coli J5 lipopolysaccharide (LPS) to human erythrocytes (RBC) and polymorphonuclear leukocytes (PMNL) was evaluated. In vitro studies indicated three things: HA-1A mediates immune adherence of 125I-J5 LPS to human RBC and PMNL in a dose dependent manner; under these conditions, high concentrations of LPS (400 ng/mL) could be specifically bound. Immune adherence occurs via the classical complement pathway as demonstrated by its calcium dependence; HA-1A-J5 LPS-C' immune complexes bound to CR1 on human RBC and PMNL. PMNL binding and internalization of immune complexes was demonstrated by trypsin stripping of externally bound immune complexes. These studies support the proposal that HA-1A can lower the bioavailability of endotoxin by mediating binding and potential clearance of LPS via human RBC through the reticuloendothelial system or via direct internalization by peripheral blood PMNL. PMID- 8450253 TI - Protection against lethal endotoxemia by anti-lipid A murine monoclonal antibodies: comparison of efficacy with that of human anti-lipid A monoclonal antibody HA-1A. AB - The protective capacities of murine anti-lipid A monoclonal antibodies (MAbs) 8-2 and 26-20 were examined and compared with those of the human MAb HA-1A with respect to inhibition of lipopolysaccharide (LPS) priming of human polymorphonuclear leukocytes (PMNL) in vitro and protection against lethal endotoxemia in mice. HA-1A did not prevent the priming effect of either rough or smooth LPS, while MAb 26-20 effectively inhibited LPS priming of human PMNL. Also, both murine MAbs protected mice against an otherwise lethal challenge with rough Re LPS of S. minnesota R595 as well as with smooth LPS of E. coli O111:B4. HA-1A exerted no protection against the lethal effects of Re LPS in this in vivo model. The enhanced survival in mice by treatment with MAbs 8-2 and 26-20 was associated with decreased levels of LPS-induced tumor necrosis factor. Neutralization of lipid A as a mechanism of protection was strongly suggested by efficacious inhibition of LPS priming of human PMNL by MAbs 8-2 and 26-20 in vitro. PMID- 8450254 TI - Tumor necrosis factor-alpha (TNF alpha) in cerebrospinal fluid from patients with meningitis of different etiologies: high levels of TNF alpha indicate bacterial meningitis. AB - The levels of tumor necrosis factor (TNF)-alpha in cerebrospinal fluid (CSF) were analyzed in 139 patients with meningitis and in 20 control subjects. Elevated concentrations were observed in 42 (82%) of 51 patients with purulent bacterial meningitis (18/24 Haemophilus influenzae, 13/14 Streptococcus pneumoniae, 7/7 Neisseria meningitidis, and 4/6 with other purulent bacterial etiology). In contrast, elevated levels were found in only 5 of 78 individuals with nonbacterial meningitis (2/8 with herpes simplex type 2, 3/3 with varicella zoster virus). Thus, the positive and negative predictive values were 0.89 for indicating a purulent bacterial meningitis. Raised CSF TNF alpha levels were observed in 7 of 8 patients with purulent bacterial meningitis in whom the routinely used parameters did not unequivocally indicate the diagnosis. Moderately increased levels were seen in 5 of 6 patients with Mycobacterium tuberculosis meningitis and in 1 of 4 cases of Borrelia burgdorferi. Thus, the present study indicates that concentrations of TNF alpha in CSF usually can discriminate between purulent bacterial and nonbacterial meningitis. These findings may contribute diagnostic guidance with routinely used CSF parameters. PMID- 8450255 TI - Impairment of neutrophil antifungal activity against hyphae of Aspergillus fumigatus in children infected with human immunodeficiency virus. AB - Human immunodeficiency virus (HIV)-infected patients may acquire invasive aspergillosis without previously recognized risk factors, such as neutropenia or corticosteroid therapy. Because neutrophils (PMNL) are an important component of host defense in aspergillosis, the antifungal activity of PMNL against hyphae of Aspergillus fumigatus in 31 HIV-infected children was assessed. Hyphal damage was unaffected in 15 HIV-infected children with age-adjusted CD4 cell counts > or = 25% of the normal median value; it was decreased in 16 with CD4 cell counts < 25% (both vs. 20 healthy controls, P = .001. Incubation with sera from 12 of 14 HIV infected children but not with the recombinant HIV proteins gp120, gp41, and p24 suppressed antifungal activity of normal PMNL compared with normal serum (P = .002). Pretreatment of defective PMNL from 5 patients with granulocyte colony stimulating factor (G-CSF) partially corrected the defect (P = .002). These findings suggest that impaired serum-mediated antifungal activity against Aspergillus hyphae exists in PMNL of HIV-infected patients with low CD4 cell counts; G-CSF may improve this activity. PMID- 8450256 TI - Surface antimicrobial activity of heparin-bonded and antiseptic-impregnated vascular catheters. AB - Most Swan-Ganz pulmonary artery catheters have heparin bonded to the surface with benzalkonium chloride, a cationic surfactant, to reduce thrombosis. Since benzalkonium is bactericidal, the antimicrobial activity of heparin-bonded pulmonary artery catheters was investigated in an in vitro assay. Each catheter exhibited activity against a wide variety of potential microbial pathogens, including Candida albicans. The magnitude of activity against individual organisms correlated strongly with their in vitro susceptibility to benzalkonium chloride (r = .94, P < .002). A chlorhexidine-silver sulfadiazine-impregnated catheter exhibited even greater activity than the heparin-bonded catheters (P = .01). When exposed to serum for 24 h, heparin-bonded catheters lost > or = 50% of their antimicrobial activity, whereas the activity of the chlorhexidine-silver sulfadiazine-impregnated catheter was minimally affected. The fortuitous surface antimicrobial activity of heparin-bonded catheters may account for the low incidence of catheter-related bacteremia (mean, 1.0%) compared with Swan-Ganz catheters of the same materials but not coated with benzalkonium-heparin (mean, 2.8%). PMID- 8450257 TI - T cell responsiveness correlates differentially with antibody isotype levels in clinical and asymptomatic filariasis. AB - To establish the relationships among T and B cell responses, active infection, and clinical manifestations in lymphatic filariasis, filarial-specific lymphocyte proliferation, IgG antibody isotypes, and IgE levels were determined in an exposed population: 31 asymptomatic amicrofilaremics, 43 microfilaremics, 12 symptomatic amicrofilaremics, and 52 elephantiasis patients. Lymphocyte proliferation was higher in elephantiasis patients and asymptomatic amicrofilaremics than in microfilaremics (P < .004). A proportion of asymptomatic amicrofilaremics (32%), elephantiasis patients (37%), and symptomatic amicrofilaremics (58%) showed antigen-specific lymphocyte unresponsiveness, and lymphocyte proliferation to filarial antigens correlated negatively with specific IgG4 levels (rho = -0.315, P < .001). As elevated specific IgG4 is an indicator of active infection, it is argued that active infection may result in lymphocyte hyporesponsiveness irrespective of clinical category. Of those with elevated specific IgE levels and high T cell proliferative responses, 70% had elephantiasis, suggesting these factors have a role in pathology. However, the existence of a proportion of elephantiasis patients with low anti-filarial IgE and T cell unresponsiveness to filarial antigens suggests that elephantiasis can be caused by distinct processes. PMID- 8450258 TI - Beyond chloroquine: implications of drug resistance for evaluating malaria therapy efficacy and treatment policy in Africa. AB - Emphasis on retaining chloroquine as the first-line therapy for Plasmodium falciparum infections in most of sub-Saharan Africa for as long as it remains effective has resulted in widespread reliance on chloroquine in areas where it can have little effect on P. falciparum parasitemia. To address this issue, clinical, parasitologic, and hematologic responses to chloroquine or pyrimethamine/sulfadoxine treatment were assessed among very young children in Malawi (n = 153) and Kenya (n = 73). The median time to resumption of clinical symptoms in chloroquine-treated children was 13.5 days in Malawi and 9.5 days in Kenya. Children treated with pyrimethamine/sulfadoxine maintained clinical improvement and had greater increases in their hemoglobin concentration during the follow-up period than did children treated with chloroquine. Treatment with chloroquine failed to produce either a durable clinical improvement or optimal hematologic recovery. Consequently, chloroquine can no longer be considered adequately effective therapy of clinical P. falciparum malaria in very young children in these areas of Africa. PMID- 8450259 TI - Heterosexual transmission as the most common route of acute hepatitis B virus infection among adults in Taiwan--the importance of extending vaccination to susceptible adults. AB - Sixty adult patients with acute viral hepatitis B (AVHB) and 93 controls were interviewed to assess potential risk factors of hepatitis B. Heterosexual contact was the only significant factor, and it was associated with 83% of cases. A history of having new sex partners or multiple sex partners within 6 months before the onset of AVHB or first sexual contact before 20 years of age were significantly associated with HBV infection (P < .005, respectively). There was a dose-response relationship between the number of sex partners and the risk of HBV infection. In multivariate analyses, a history of having new sex partners was the most important factor. Moreover, 18 of 24 sex partners of the patients were serum hepatitis B surface antigen- and HBV DNA-positive. Heterosexual contact is, therefore, the predominant route of HBV transmission among adults in Taiwan. Susceptible adults should receive vaccination. PMID- 8450260 TI - A common-source outbreak of callitrichid hepatitis in captive tamarins and marmosets. AB - Callitrichid hepatitis (CH) is a highly fatal, emerging arenavirus disease of captive South American marmosets and tamarins (Callitrichidae), including the endangered golden lion tamarin. A common-source outbreak of CH in golden lion tamarins and pygmy marmosets at a US zoo resulted from a single feeding of the primates with newborn mice in apparently infected with lymphocytic choriomeningitis virus (LCMV). Isolates from livers of mice and primates were related to isolates from previous CH outbreaks and to laboratory strains of LCMV by serology and nucleic acid hybridization, and 2 surviving animals developed antibody to other LCMVCH isolates and to laboratory strains of LCMV. Thus, LCMV, an arenavirus prevalent in wild mice in the US, can cause sporadic fatal hepatic disease in primates. Exposure of humans to wild or laboratory mice or to marmosets and tamarins that are infected with wild-type strains of LCMV poses the danger of serious disease. PMID- 8450261 TI - Determination of human T lymphotropic virus type by polymerase chain reaction and correlation with risk factors in northern California blood donors. AB - To determine the relative prevalence of human T lymphotropic virus (HTLV) types I and II, type-specific polymerase chain reaction (PCR) was done on seropositive northern California blood donors. From October 1988 through March 1990, 67 (0.055%) of 122,517 blood donors had confirmed HTLV antibody. Seropositive donors were more likely to be middle-aged, female, and nonwhite than the overall donor base. PCR of samples from 30 HTLV-seropositive donors yielded 19 (63%) with HTLV II and 9 (30%) with HTLV-I; 2 (7%) were repeatedly negative by PCR. HTLV-I infected subjects had ancestry (n = 3), sexual contact (n = 3), or paternal military service in (n = 1) Japan or the Caribbean. HTLV-II carriers reported past intravenous drug abuse (n = 3) or sex with a drug user (n = 11). Two carriers of each type reported previous blood transfusions, and 1 HTLV-II carrier was a dentist with no other risk factors for retroviral infection. PMID- 8450262 TI - Mode of inoculation of the Lyme disease agent Borrelia burgdorferi influences infection and immune responses in inbred strains of mice. AB - Mice were infected with Borrelia burgdorferi by infection via Ixodes ricinus and experimental inoculation to determine whether transmission rates of spirochetes and antibody responses are influenced. Mice infected by the natural route were substantially more infective for ticks; two- to sixfold more tick larvae were positive for B. burgdorferi than those fed on experimentally inoculated mice. In natural infection, spirochetemia may be greater or spirochetes may be more accessible for transmission. Thus, this form of xenodiagnosis could be used to determine levels of spirochetes in the vertebrate host. Similar levels of antibody were present in all mice; however, those infected by the natural route lacked antibodies to outer surface proteins (Osp) A and B. The small antigen dose given through a tick bite may not have been sufficient to induce rapid OspA or OspB antibodies, thereby allowing the later development of higher levels of spirochetemia. PMID- 8450263 TI - Increase in activated T cells and reduction in suppressor/cytotoxic T cells in acute rheumatic fever and active rheumatic heart disease: a longitudinal study. AB - In a prospective study, patients with acute rheumatic fever (ARF) and active rheumatic heart disease (ARHD) showed a significant increase in CD4+ T cells, CD22+ B cells, and CD4:CD8 cell ratio but a significant decrease in the percentages of CD8+ and CD3+ T lymphocytes compared with patients with quiescent RHD (CRHD) or streptococcal pharyngitis (SP) and normal controls. The proportion of interleukin-2 receptor (IL-2R)+ (CD25+) cells was higher in peripheral blood mononuclear cell cultures (both before and after phytohemagglutinin stimulation) of ARF and ARHD patients than in those of CRHD or SP patients or controls; this finding persisted up to 48 weeks. In ARF patients, the percentage of CD8+ cells returned to within normal range at 48 weeks. Furthermore, the percentage of IL 2R+ cells correlated positively with the percentage of CD4+ but not of CD8+ lymphocytes, suggesting that helper/inducer T cells are in an immunologically activated state and may account for aberrations in the distribution of lymphocyte populations in peripheral blood of ARF and ARHD patients. PMID- 8450264 TI - Decreased CD4+CD29+ (memory T) cells in patients with chronic granulomatous disease. AB - By the use of flow cytometry, 17 patients with chronic granulomatous disease (CGD) were examined for lymphocyte subsets. CD4+CD29+ cell (memory T cell) and CD8+CD11b+ cell (suppressor T cell) subsets in CGD were significantly decreased and remained practically unchanged throughout the period examined except in those < 6 months of age, although in controls both subsets gradually increased with age. These data indicate a certain abnormality in the maturation process of CGD T lymphocytes. Memory T cells are known to secrete a large amount of interferon gamma (IFN-gamma). Recently, administration of IFN-gamma to CGD patients has become an effective treatment that reduces the frequency of serious bacterial infections. Decreased memory T cells may clarify the mechanism of therapeutic effectiveness, which remains unknown. PMID- 8450265 TI - Kaposi's sarcoma in a human immunodeficiency virus-negative patient with asymptomatic human T lymphotropic virus type I infection. PMID- 8450266 TI - False-positive ELISA for human immunodeficiency virus after influenza vaccination. PMID- 8450267 TI - Association of antibody responses to the 19-kDa antigen of Mycobacterium tuberculosis and the HLA-DQ locus. PMID- 8450268 TI - Blood group antigen secretion and gallstone disease in the Salmonella typhi chronic carrier state. PMID- 8450269 TI - [Infection rate of Chlamydia trachomatis in sexual partners from pregnant women with Chlamydia trachomatis infection]. AB - We investigated the infection rate of Chlamydia trachomatis in sexual partners who had pregnant wives with C. trachomatis diagnosed by means of serum-antibody test (Ipazyme) or antigen test (Chlamydiazyme, IDEIA-chlamydia). Antibody positive rate was 60.4% (90/149 cases), and antigen-positive rate was 7.4% 11/149 cases). All cases with Chlamydial antigen had anti-Chlamydial antibody. Eleven cases with Chlamydial antigen had no symptom of urethritis. Among these cases, eight cases had abnormal laboratory findings. However, the other three cases who had no abnormal finding were careers of C. trachomatis. In this study, sexual partners who had Chlamydial antigen were few, however, those who had anti chlamydial antibody were many. Therefore, C. trachomatis will disseminate among many families as a latent infection. PMID- 8450270 TI - [Detection of mecA gene of methicillin resistant staphylococci from oral swabs by polymerase chain reaction]. AB - We evaluated the polymerase chain reaction method (PCR) for the rapid detection of methicillin resistant Staphylococcus aureus (MRSA), and compared it with the conventional culture method. Primers for amplification of mecA gene were synthesized by DNA synthesizer according to the published sequences of mecA gene. The results were as follows: Specificity of PCR was excellent, as there was no cross-reaction with any organism other than MRSA. Fifty colony forming units of MRSA were detected, indicating good sensitivity. We examined oral swabs from 13 bed-ridden patients (age range: 65-82 yrs) by PCR and the conventional culture method. The PCR elicited positive results in 6 out of 13 cases. MRSA or coagulase negative Staphylococci (CNS) in Mueller-Hinton agar containing 12.5 micrograms/ml methicillin were obtained from all of these PCR-positive specimens. Two of 7 PCR negative specimens raised MRSA or CNS colonies, but the number of colonies from these specimens was below the sensitivity threshold of the PCR. The good specificity and sensitivity of the PCR method for the detection of mecA gene obtained in this study suggest the possibility of application of this method for detection of MRSA in clinical specimens. PMID- 8450271 TI - [Effect of erythromycin on anti staphylococcal activity and dye production of Pseudomonas aeruginosa isolated from clinical materials]. AB - Anti staphylococcal activity by Pseudomonas aeruginosa was investigated through the use of the reversed agar plate and the filter paper stamp methods. Investigation was also conducted on the dye production of different clinical isolates of Pseudomonas aeruginosa, the relationship between drug susceptibility and anti staphylococcal activity, and the influence of erythromycin on anti staphylococcal activity. Seventy four strains of Pseudomonas aeruginosa were prepared which included 20 strains from pus, 34 strains from sputum and 20 strains from urine. These were then inoculated with methicillin resistant Staphylococcus aureus (MRSA). They were then cultured for 48 hours by using the reversed agar plate and the filter paper stamp methods. Anti staphylococcal activity was observed in 16 strains from pus (80%), 19 strains from sputum (55.9%) and 8 strains from urine (40%). The Pseudomonas aeruginosa strains which have no pigment tended to show poor anti staphylococcal activity. Drug susceptibility was tested using PIPC, AMK, IPM, CFS and OFLX. The strains which showed resistance to OFLX tended to show poor anti staphylococcal activity. Erythromycin inhibited the dye production of Pseudomonas aeruginosa but exhibited no effect on anti staphylococcal activity. Consequently, these results suggest erythromycin has exhibited a previously unknown pharmacological effect, furthermore, anti staphylococcal activity was not caused by pigmentation only. PMID- 8450272 TI - [Clinical study on postoperative infections caused by methicillin-resistant Staphylococcus aureus after gastrointestinal surgery]. AB - We studied 308 postoperative infections (216 patients) after gastrointestinal surgery during 1987-1991, to elucidate the incidence of postoperative infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and its correlation to clinical background factors. Results were as follows: (1) MRSAs were isolated from 25.9% out of 216 patients or 22.4% out of 308 infections. (2) The isolation rate of MRSA was significantly high in infectious enterocolitis (64.7%, p < 0.001), intraabdominal infections (52.5%, p < 0.001) and respiratory tract infections (35.3%, p < 0.05). On the other hand, it was significantly low in bacteremias (9.28%, p < 0.001), wound infections (13.6%, p < 0.05) and urinary tract infections (3.33%, p < 0.05). (3) MRSAs were found more frequently in male (p < 0.05), younger patients (p < 0.05) and patients with malignant disease (p < 0.10). Whereas no difference was recognized between patients with or without complication. (4) The isolation rate of MRSA by the kind of antibiotics used after surgery, was 0% (0/20, the 1st generation cephems), 17.2% (10/58, the 2nd generation cephems) and 54.5% (48/88, the 3rd generation cephems). Significant differences were found among each group (p < 0.05, p < 0.001). (5) During 1990 1991 when the 1st generation cephems were used frequently, MRSAs were found significantly lower in frequency than during 1987-1989 (p < 0.05). Especially a marked decrease in the rate of MRSA (51.4% to 8.33%, p < 0.05) was seen among patients after upper gastrointestinal surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450274 TI - [Hospital infection with methicillin-resistant Staphylococcus aureus (MRSA) in Saga Medical School Hospital, a rapid increase in coagulase type-VIII strains]. AB - Hospital infection with MRSA has increased in Saga Medical School Hospital. The causative MRSA consisted predominantly of coagulase type-II strain before 1989, but after 1990, coagulase type-VII MRSA increased rapidly. This type-VII strain has marked multiple drug-resistance, and the pattern of drug sensitivity of MRSA in this hospital was different from that of MRSA detected in other facilities, which are clinically serious problems, therefore, we conducted an etiological study of the background of the increase in MRSA infection in our hospital. The results of the study are summarized as follows: 1) The proportions of MRSA (on strain from one patient) to all types of S. aureus detected in the hospital were 26% for 1986, 23% for 1988, 37% for 1989, 30% for 1990 and 60% for 1991. The proportion increased greatly in 1991. 2) Coagulase type VII-MRSA was first detected only in 5 patients in 1989, then it tended to spread, and this type (probably derived from the same strain) accounted for 47% of MRSA infection in patients examined in 1991. 3) The study of the drug sensitivity pattern and etiological survey of the infection showed that coagulase type VII-MRSA prevalent in the hospital consisted of two types: CLDM, and EM-sensitive, IPM/CS, and MINO resistant and TSST-1 non-producing and enterotoxin non-producing type, and CLDM, and EM-sensitive, IPM/CS, and MINO-resistant and TSST-1 non-producing type with enterotoxin serotype A. 4) Coagulase type VII-MRSA (Probably derived from the same strain) was detected in physicians and nurses working in affected wards and also in the patients's room.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450273 TI - [Large scale outbreak of Yersinia pseudotuberculosis serotype 5a infection at Noheji-machi in Aomori Prefecture]. AB - In June 1991, there were large scale outbreaks of Yersinia pseudotuberculosis at 4 primary schools and 1 junior high-school in Noheji-machi in Aomori Prefecture. A total of 732 patients (725 pupils and school children, 7 teachers and personnel) were affected and 134 were hospitalized. Sex ratio of incidence was 1.1:1.0 without appreciable difference. Clinical symptoms (478 patients) were represented frequently by pyrexia (86.4%), eruption (73.8%), abdominal pain (66.7%), vomiting nausea (63.4%), etc., and were characterized by a strawberry tongue, pharyngeal redness, membranous desquamation of the fingers and arthralgia during convalescence. Yersinia pseudotuberculosis was isolated from 27 (81.8%) of 33 patients stool specimens, 1 waste water specimen and 2 (11.7%) of cooking employees' stool specimens. The isolates were confirmed serotype 5a, and positive for calcium-dependency and autoagglutination, and harboring 40-50 megadalton virulent plasmid. Restrictive endonuclease digestive pattern of plasmid proved to be identical. In many cases, patients' serum antibody titer showed a significant increase ratio to the isolated strain. In term of drug susceptibility, all the strains were sensitive to cefem, penicillin and amino-glycoside series and resistant to macrolide and sulfa series. The infectious source was limited to the school feeding, but the responsible food remained unknown. Mean latency and exposure day were presumed to be 6.5 days and May 30, respectively. PMID- 8450275 TI - [A case of Campylobacter fetus subspecies fetus meningitis]. AB - A 40-year-old male with no history of underlying disease was admitted to Hokusho Central Hospital on May 25, 1991, complaining of high fever and headache. Physical examination on admission revealed a temperature of 38.5 degrees C, a pulse rate of 84 beat/min (relative bradycardia) and no abnormal findings for the chest or abdomen. Slight neck stiffness without Kernig's sign was observed at neurological examination. Laboratory data were: ESR 11 mm/lh, WBC 12000/mm3, C reactive protein positive. Lumbar puncture showed an initial pressure of 230 mmH2O; CSF revealed a cell count of 2633/3 mm3 with mononuclear pleocytosis, total protein of 76 mg/dl and sugar of 54 mg/dl (CSF:blood glucose ratio 0.47). We initially suspected tuberculous or cryptococcal meningitis, but Campylobacter fetus subsp. fetus (C. fetus) was isolated from the CSF and venous blood on the 27th hospital day. IPM/CS 1 g/day, MINO 200 mg/day and FOM 4 g/day were intravenously administered. This antibiotic therapy was very effective: the patient was soon afebrile, and gradually all signs and symptoms were resolved. C. fetus was sensitive to IMP/CS, MINO, KM, GM, EM, OFLX, CP. The patient was discharged with no complication. He has eaten raw beef frequently before admission, but stool culture for C. fetus was negative. PMID- 8450276 TI - [Effect of erythromycin on neutrophil adhesion molecules]. AB - The mechanisms of erythromycin (EM) in chronic lower respiratory tract diseases including diffuse panbronchiolitis (DPB) has been reported. In this study we investigated the effect of EM on peripheral neutrophil adhesion molecules such as LFA-1 and Mac-1 obtained from six healthy subjects. Pretreatment of neutrophils with each concentration (10 ng/ml approximately 100 micrograms/ml) of EM resulted in no significant reduction in the expression of LFA-1 alpha, beta and Mac-1. Moreover, EM had no capability of reducing these expressions even when neutrophils were pretreated with 1 microgram/ml of EM at time from 0 to 60 min. These findings indicate that EM does not directly reduce the expression of LFA-1 alpha, beta and Mac-1 on peripheral neutrophil obtained from healthy subjects. PMID- 8450277 TI - [A case of spontaneous bacterial peritonitis with ascites caused by hypoproteinemia after a massive bleeding from a gastric ulcer]. AB - A case of spontaneous bacterial peritonitis (SBP) developed in an old man whose ascitic fluid was related neither to portal hypertension nor nephrotic syndrome, but with severe hypoalbuminemia emerged after a massive bleeding from a gastric ulcer in a malnutrition state. Ascitic fluid, increasing day by day, yielded Enterobacter cloacae and Bacteroides fragilis. Though autopsy was not carried out because of refusal of his family, neither liver necropsy, nor abdominal CT scan nor repeated abdominal ultrasonography showed findings suggesting existence of liver cirrhosis. In the presence of his ascites, the extent of a chemiluminescence (CL) response of polymorphonuclear cells from volunteers was significantly lower than that of his serum. This report shows that SBP can develop in a patient with ascites unrelated to portal hypertension when ascitic fluid induces little CL response. PMID- 8450278 TI - [A case of liver abscess associated with endophthalmitis caused by Klebsiella pneumoniae]. AB - A 54-year-old female was admitted to our hospital because of a spiking fever, right hypochondriac pain, right orbital pain and visual disturbance. Before admission she was treated with systemic antibiotics infusion for a diagnosis of liver abscess at the other hospital and the liver abscess almost diminished for a while. With the diagnosis of liver abscess and endophthalmitis, liver drainage and evisceration were carried out. The culture of pus from the eye and liver yielded K. pneumoniae. After liver drainage, evisceration, and direct injection of antibiotics into the eye, inflammatory findings tended to improve. Seven cases of metastatic K. pneumoniae endophthalmitis have been reported so far in Japan. The cases had liver abscess as the primary disease and 3 cases had bilateral endophthalmitis. Five cases with liver abscess survived except one who died of sepsis, but unfortunately, all cases became blind in the affected eyes. The prognosis of bacterial endophthalmitis, especially associated with K. pneumoniae liver abscess, is poor and as the outcome could appear to depend on time when treatment is started, a more aggressive diagnostic approach is required. Moreover systemic antibiotic infusion alone is inadequate for treatment of liver abscess and endophthalmitis, and liver drainage, evisceration and intravitreal injection of antibiotics must be given in early stage. PMID- 8450279 TI - [A case of cat scratch disease: from the clinical pathological point of view]. AB - We described a forty-four-year-old female who was scratched by her cat, and developed lymphadenopathy. Cat scratch disease skin-test was positive. Cat scratch disease is well known, but there are not many reports in Japan. Reports of cat scratch disease will increase as the pathogen was recently detected. Attention must be drawn to zoonosis containing cat scratch disease. PMID- 8450281 TI - [Molecular genetics of Alzheimer's disease]. PMID- 8450280 TI - [A case of pulmonary aspergillosis by immunodiagnosis during remission induction therapy of acute myelocytic leukemia]. AB - The frequency of a visceral mycosis grows definitely higher with an immunocompromised host. Invasive fungal infection can be controlled by means of development of early diagnosis and antifungal therapy. In these types of cases, it is difficult to establish an antemortem diagnosis of invasive pulmonary aspergillosis and most of them were diagnosed postmortem. A patient was diagnosed as aspergillosis from the clinical and serological features. This patient underwent successful therapy during remission induction therapy of acute myelocytic leukemia (AML). A 26-year-old male was admitted to our hospital because of leukocytosis with a diagnosis of AML made by reviewing peripheral blood smears and bone marrow aspirate. After remission induction therapy, he was still febrile in spite of treatment with a broad spectrum antibiotics and empiric therapy of fluconazole. Unfortunately shadowing appeared on the chest radiograph and aspergillus antigen was detected from the serum and the sputum. Consequently, the patient who suffered from invasive pulmonary aspergillosis was diagnosed and treated with intravenous amphotericin B and flucytosine. The radiological shadow improved but AML relapsed, therefore, remission induction therapy of AML was started again but he died of sepsis caused MRSA. In the postmortem histopathological examination the lung tissues, the hyphae could not be confirmed while, in immunohistochemical examinations of the lesion at the left S8, aspergillus antigens were detected around the small necrotic lesions and in the polymorphologic giant cells. We emphasize that invasive pulmonary aspergillosis is very difficult to diagnose whereas active examinations and clinical early diagnosis may lead to more effective therapy and the prognosis. PMID- 8450282 TI - [Role of phosphatidylcholine breakdown by phospholipase C, D in signal transduction]. PMID- 8450283 TI - [Expression of new members of the prolactin-growth hormone gene family in placenta]. PMID- 8450284 TI - [Nonisotopic PCR-SSCP technique with silver staining and gradient gel electrophoresis]. PMID- 8450285 TI - [The highly sensitive zymogram method for detection of endonuclease isozymes: application of dried agarose film overlay (DAFO) method for biochemical analysis of both DNase and RNase isozymes]. PMID- 8450286 TI - [Molecular biology of sideroblastic anemia and porphyria]. PMID- 8450287 TI - Organization of a clinical trial. PMID- 8450288 TI - Scientific dishonesty--the need for precise concepts and effective tools. PMID- 8450289 TI - Pathophysiological mechanisms for restenosis following coronary angioplasty: possible preventive alternatives. AB - Restenosis after successful percutaneous transluminal coronary angioplasty (PTCA) remains an unsolved medical problem. The search for the underlying pathophysiological mechanisms have identified intimal proliferation of smooth muscle cells (SMC) to be the prevailing cause of late restenosis, with endothelial cells (EC) and platelets being important participators in the process. According to the most accepted present theory, SMC would be stimulated to migrate and proliferate shortly after the angioplasty by the release of growth factors from injured EC and accumulated platelets. However, clinical trials of agents interfering with these mechanisms have not significantly diminished the rate of restenosis, which suggest both that our knowledge of the process is incomplete, and that new ways of administering the agents may be required. PMID- 8450290 TI - Modified forms of low-density lipoprotein and atherosclerosis. PMID- 8450291 TI - Venographic assessment of deep vein thrombosis and risk of developing post thrombotic syndrome: a prospective study. AB - It is well known that patients with deep vein thrombosis (DVT) constitute a risk group for development of pulmonary embolism. However, the relation of DVT and the extent thereof with the subsequent sequelae (post-thrombotic syndrome) are insufficiently investigated. We have prospectively studied a series of consecutive patients admitted because of DVT on lower limbs, trying to correlate venographic findings during acute DVT with post-thrombotic (PTS) symptoms that develop later. Seventy-nine patients (84 limbs) with acute DVT were followed-up in our out-patient clinic at 4-monthly intervals for 3 years. At each visit patients were carefully examined regarding the appearance of PTS symptoms and/or signs from the DVT-affected leg. Three years after discharge, presence of PTS signs was assessed according to a simple scoring system. And then correlated to venographic findings during acute DVT. Patients were classified as having no (37 legs), mild (30 legs), or severe PTS signs (17 legs). Patients with popliteal vein involvement showed a significantly higher incidence of PTS 3 years later (P < 0.001). The risk of PTS also increased as DVT extent increased (P < 0.001). Nevertheless, the logistic regression analysis showed that DVT location explained all the differences (P < 0.001). In other words, DVT extent was overriden by the significance of DVT location, being popliteal the only location that showed a relevant contribution to the PTS incidence (95% confidence interval = 2.49-71.5). PMID- 8450292 TI - Cardiovascular risk factors in treated hypertensives--a nation-wide, cross sectional study in Sweden. AB - Hypertensive patients still face a considerable risk of cardiovascular disease in spite of drug treatment in many studies. This may partly be explained by metabolic disturbances, both primarily linked to hypertension but also secondarily influenced by anti-hypertensive drugs themselves. In order to evaluate residual cardiovascular risk factors we investigated 1915 treated hypertensives (912 males, 1003 females) attending 128 health centres from all parts of Sweden. Mean blood pressure was 148/91 mmHg for males and 151/90 for females, but a substantial proportion of all patients were not well controlled, having a diastolic blood pressures > or = 100 mmHg (17% males, 12% females). Total cholesterol and HDL-cholesterol were 6.03 and 1.25 mmol l-1 for males, and 6.40 and 1.50 for females. The corresponding figures for serum triglycerides were 2.03 and 1.72 mmol l-1, respectively. In all, 38% of the hypertensives had hypercholesterolaemia (> or = 6.5 mmol l-1) and 27% hypertriglyceridaemia (> or = 2.3 mmol l-1). The lipid/lipoprotein findings may also be influenced by the various anti-hypertensive drugs used in Sweden. The prevalence of smoking and diabetes mellitus were 25% and 11% for men, and for women 24% and 9%. In conclusion, Swedish hypertensives show evidence of significant residual cardiovascular risk factors in spite of treatment. This may be of importance for future relative and absolute cardiovascular risk. It is time to re-evaluate the effectiveness of our management and care of hypertensive patients. PMID- 8450293 TI - Anaphylactoid shock following Hymenoptera sting as a presenting symptom of systemic mastocytosis. AB - Systemic mastocytosis is a rare and chronic disorder characterized by a pathologically increased number of mast cells in various tissues and overproduction of mast cell mediators. From a group of 15 patients (10 females, 5 males) with systemic mastocytosis five female patients presented with a history of an anaphylactoid shock reaction to wasp sting. Three of them had no demonstrable specific IgE against wasp or bee venom in serum, and a skin test that was only weakly positive for wasp venom. One patient had specific IgE against wasp venom and a clearly positive skin test to wasp venom. The other patient had specific IgE against both wasp and bee venom and a skin test that was only weakly positive to wasp venom. Two patients had to stop a hyposensitization procedure because of systemic side effects. The five patients did not differ from the other patients with systemic mastocytosis with regard to either clinical symptoms and signs or urinary excretion of histamine metabolites. From the latter group two female and three male patients said they had been stung by a wasp in the past. Thus, anaphylactoid shock after Hymenoptera sting can be a presenting symptom of systemic mastocytosis and may be caused by an IgE- as well as a non IgE-mediated mechanism. In cases of anaphylactoid reaction to Hymenoptera sting, especially when there is no IgE demonstrable in serum or in cases of intolerance of hyposensitization, the diagnosis of systemic mastocytosis should be considered, also in the absence of the clinical hallmarks of urticaria pigmentosa. PMID- 8450294 TI - Modulation of the haematopoietic toxicity associated with zidovudine in vivo with lithium carbonate. AB - The drug zidovudine (AZT), a synthetic thymidine analogue, has been used in the treatment of acquired immunodeficiency syndrome (AIDS). Clinical use of zidovudine has induced haematopoietic toxicity manifested by anaemia, neutropenia, and overall bone marrow suppression. The monovalent cation lithium has been shown to be an effective agent capable of modulating several aspects of haematopoiesis such as the induction of neutrophilia, thrombopoiesis, and protection against suppression of hematopoietic progenitor stem cells following exposure to anti-cancer drugs and/or radiation at doses commonly used in the treatment of malignant disease. We report here the result of studies designed to evaluate the effectiveness of lithium in reversing zidovudine-induced haematopoietic suppression when administered to normal mice in vivo in the presence of dose-escalation zidovudine. Lithium carbonate (Li2CO3) reversed zidovudine toxicity as measured by increases in peripheral WBC, platelets, and CFU-GM and CFU-Meg haematopoietic progenitors; however lithium was insufficient in reversing the reduction of erythropoiesis associated with zidovudine use in vivo. These results further confirm the effective use of lithium to reverse the development of myelosuppression and thrombocytopenia associated with the anti viral drug zidovudine, but is less effective in ameliorating the induction of anaemia. PMID- 8450295 TI - Apparent absence of stroke and ischaemic heart disease in a traditional Melanesian island: a clinical study in Kitava. AB - On the island of Kitava, Trobriand Islands, Papua New Guinea, a subsistence lifestyle, uninfluenced by western dietary habits, is still maintained. Tubers, fruit, fish and coconut are dietary staples. Of the total population, 1816 subjects were estimated to be older than 3 years and 125 to be 60-96 years old. The frequencies of spontaneous sudden death, exertion-related chest pain, hemiparesis, aphasia and sudden imbalance were assessed by semi-structured interviews in 213 adults aged 20-96. Resting electrocardiograms (ECG's) were recorded in 119 males and 52 females. No case corresponding to stroke, sudden death or angina pectoris was described by the interviewed subjects. Minnesota Code (MC) items 1-5 occurred in 14 ECG's with no significant relation to age, gender or smoking. ST items (MC 4.2 and 4.3) were found in two females and Q items (MC 1.1.2, 1.3.2 and 1.3.3) in three males. Stroke and ischaemic heart disease appear to be absent in this population. PMID- 8450296 TI - Hyperammonaemic encephalopathy as the presenting feature of IgD multiple myeloma. AB - We observed a case of hyperammonaemic encephalopathy in a patient without liver dysfunction which revealed meningeal involvement of IgD multiple myeloma. We have reviewed briefly the hyperammonaemic syndrome and we believe that this diagnosis has to be considered in differential diagnosis of encephalopathies in patients with multiple myeloma. PMID- 8450297 TI - HLA-DR3, DQ2 homozygosity in two patients with insulin-dependent diabetes mellitus superimposed with ulcerative colitis and primary sclerosing cholangitis. AB - Two unrelated young males with the unusual simultaneous presence of insulin dependent diabetes mellitus, ulcerative colitis and primary sclerosing cholangitis are reported. Both patients manifested homozygosity for the DR3-DQw2 (DQB*0201) HLA genotypes. We believe that homozygosity for this genotype may predispose for this type of multi-organ autoimmune disease. PMID- 8450298 TI - Severe skin necrosis following warfarin therapy in a patient with protein C deficiency. AB - A female patient with a history of both arterial and venous thrombosis developed extensive skin necrosis following warfarin treatment. When protein C deficiency was diagnosed, successful anticoagulation with warfarin was achieved by prolonging the course of intravenous heparin and introducing warfarin therapy with a low initial dose which was gradually increased. Aspects of the pathogenic mechanism are discussed. PMID- 8450299 TI - Antiphospholipid antibodies and ischaemic heart disease. AB - Antiphospholipid antibodies (APA) have been detected in various conditions including venous and arterial thrombosis, recurrent fetal loss, thrombocytopenia and cardiac valvular lesions. APA were initially found in patients with systemic lupus erythematosus (SLE) but later have been demonstrated also in patients without connective tissue disease. We report the extensive evaluation of a 24 year-old otherwise healthy male with APA and a family history of SLE who presented with severe ischaemic heart disease requiring coronary by-pass surgery. PMID- 8450300 TI - Acute renal failure due to carnitine palmitoyltransferase deficiency. AB - A young, apparently healthy, soldier developed acute muscle weakness and rhabdomyolysis following prolonged exercise. The resultant myoglobinuria caused severe acute renal failure. Further investigation revealed the presence of carnitine palmitoyltransferase deficiency as the cause of the rhabdomyolysis. Renal function subsequently returned to normal. This rare metabolic disorder should be considered in cases of unexplained myoglobinuria and renal failure. PMID- 8450301 TI - Unstable haemoglobin causing haemolytic anaemia: de novo mutation in Sweden identified by PCR. AB - A 38-year-old Swedish woman was investigated because of mild anaemia resistant to iron therapy. Mild haemolytic disease was found by routine blood tests. Neither HPLC (HbA1c quantification) nor Hb-electrofocusing revealed any major abnormal fraction, although in vitro testing of haemoglobin instability indicated the presence of unstable haemoglobin. PCR was used to amplify coding regions of the beta globin gene. Direct nucleotide sequencing of this material revealed heterozygosity for a substitution corresponding to the haemoglobin variant alpha 2 beta 2 135(H13)Ala-->Pro. This clearly unstable variant, named Hb Altdorf, has earlier been described only in a family of Italian descent. Examination of beta globin genes from six family members of the proposita by PCR followed by specific cleavage with the restriction enzyme Ban I, revealed the mutation in her two children but not in her parents or siblings. This case demonstrates that haemoglobin variants can not be ruled out as a cause of haematological disease even if the parents lack symptoms and standard tests, such as HPLC and electrophoresis/electrofocusing, do not reveal major abnormalities. PMID- 8450302 TI - Acquired haemophilia and rheumatoid arthritis: success of immunoglobulin therapy. PMID- 8450303 TI - Regulation of the expression of a pelA::uidA fusion in Erwinia chrysanthemi and demonstration of the synergistic action of plant extract with polygalacturonate on pectate lyase synthesis. AB - The phytopathogenicity of Erwinia chrysanthemi is chiefly supported by the production of pectate lyase isoenzymes, encoded by the pel genes. One of these enzymes, PelA, encoded by the pelA gene, seems to represent only a small part of the total pectate lyase activity, but is required for full bacterial pathogenicity. To study the regulation of pelA gene expression, a pelA::uidA gene fusion was constructed. Expression of this fusion was analysed under various growth conditions and in various genetic backgrounds. Whatever the culture conditions, the pelA gene was weakly expressed. Moreover, pelA expression seems not to be regulated by the pecS gene product, but essentially by the kdgR gene product. In many plant-associated bacteria, genes involved in pathogenicity are induced by certain plant compounds. In this work, we demonstrate that E. chrysanthemi pel genes are induced in the presence of plant extracts, but only in synergy with known pectate lyase inducers (KDG: 2-keto-3-deoxygluconate; DKII: 2,5-diketo-3-deoxygluconate). However, different pel genes did not exhibit the same sensitivity to plant signal molecules. Partial purification of inducing plant compounds suggested that plant extracts contain at least one molecule involved in pectate lyase induction. This compound is thermoresistant, and has a low molecular mass and a very hydrophilic behaviour. PMID- 8450304 TI - Rhodobacter capsulatus puc operon: promoter location, transcript sizes and effects of deletions on photosynthetic growth. AB - Gene deletions of the puc operon of Rhodobacter capsulatus showed that the pucC and pucE genes, but not pucD, were required for formation of wild-type levels of the LHII complex. Deletion of pucC or pucE also impaired photosynthetic growth. The effects of pucC deletion were suppressed by secondary mutations that mapped outside the puc operon. Fusion of a lac'Z gene to pucE' showed that most of pucE transcription originated from upstream of pucB. RNA blot analysis revealed a 2.4 kb transcript that hybridized to probes specific for the pucBA, pucC and pucDE regions, indicating that some puc operon messages extend from just before the pucB gene to just after the pucE gene. PMID- 8450305 TI - Cloning and characterization of the altA alpha-tubulin gene of Physarum. AB - A cDNA clone derived from the altA locus, encoding one of several alpha-tubulins in Physarum, was sequenced and used to determine the developmental and cell cycle expression patterns of its corresponding gene. The predicted amino acid sequence of the altA gene product, alpha 1A-tubulin, is 92% identical to the other known Physarum alpha-tubulins, alpha 1B and alpha 2B, which are products of two tightly linked genes at the altB locus. The nucleotide sequence of the altA coding region is 82% identical to the two altB genes. Expression of the altA gene was found in all three cell types examined - amoeba, flagellate and plasmodium - but at substantially different levels in each. The peak level of altA message detected in flagellates was 14-fold higher than in amoebae, while the peak level in plasmodia was 5-fold lower than in amoebae. The expression pattern of altA and the predicted amino acid sequence of the alpha-tubulin it encodes suggest that alpha 1A is the substrate for post-translational acetylation, giving rise to the alpha 3-tubulin isoform found specifically in amoebae and flagellates. Northern blot analysis of plasmodial RNA samples from specific times in the cell cycle showed that the level of altA message varies over the cell cycle in a pattern similar to transcripts from other tubulin genes, with a peak at mitosis and little or no message detected during most of interphase. PMID- 8450306 TI - Functional analysis of the outB gene of Bacillus subtilis. AB - Three additional alleles of the outB gene of Bacillus subtilis, whose activity is required for spore outgrowth, were identified. The nucleotide sequence of three mutant genes was determined. Analyses of dominance-recessivity showed that the wild-type allele is dominant over the mutant ones. When the outB gene was placed under the control of the inducible spac-1 promoter, the presence of IPTG was necessary to obtain normal growth. The results suggested that the outB gene is required for growth of B. subtilis. Expression of outB from the sporulation promoter spoIID negatively affected subsequent spore outgrowth, without altering vegetative growth and sporulation. PMID- 8450307 TI - Molecular cloning and nucleotide sequence of the gene encoding a calcium dependent exoproteinase from Bacillus megaterium ATCC 14581. AB - The gene nprM encoding the calcium-dependent extracellular proteinase from Bacillus megaterium ATCC 14581 was cloned in the vector pBR322 and expressed in Escherichia coli HB101. The DNA sequence of the cloned 3.7 kb fragment revealed only one open reading frame consisting of 1686 bp with a coding capacity of 562 amino acid residues. A predicted Shine-Dalgarno (SD) sequence was observed 9 bp upstream from the presumptive translation start site (ATG). A possible promoter sequence (TAGACG for the -35 region and TATAAT for the -10 region) was found about 69 bp upstream of the ATG start site. The deduced amino acid sequence exhibited a 24 amino acid residue signal peptide and an additional polypeptide 'pro' sequence of 221 amino acids preceding the putative mature protein of 317 amino acid residues. Amino acid sequence comparison revealed 84.5% homology between the mature protein and that of a thermolabile neutral protease from B. cereus. It also shares 73% homology with the thermostable neutral proteases of B. thermoproteolyticus and B. stearothermophilus. The zinc-binding sites and the catalytic residues are completely conserved in all four proteases. NprM has a temperature optimum of 58 degrees C, a pH optimum of between 6.4 and 7.2, and is stimulated by calcium ions and inhibited by EDTA. These results indicate that the enzyme is a neutral (metallo-) protease. PMID- 8450308 TI - Characterization of the recA gene from Pseudomonas fluorescens OE 28.3 and construction of a recA mutant. AB - The recA gene of Pseudomonas fluorescens OE 28.3 was isolated by complementation of the Fec- phenotype of recombinant lambda EMBL3 phages in a RecA- Escherichia coli strain. The subcloned recA restored resistance to UV and methyl methanesulphonate (MMS) exposure in recA mutants of E. coli. DNA sequence analysis showed that the coding region of the P. fluorescens gene, specifying a protein of 352 amino acid residues, was preceded by an SOS box highly similar to those of Pseudomonas aeruginosa and Azotobacter vinelandii. The deduced amino acid sequence displayed highest homology to the RecA proteins from P. aeruginosa (87.8% identity) and A. vinelandii (84.3% identity). In both the regulatory region and the structural gene, a relatively high degree of sequence divergence from the Pseudomonas cepacia gene was observed. A mutant of P. fluorescens was constructed by inserting a kanamycin resistance cassette into its recA gene. This mutant exhibited an increased sensitivity to UV irradiation and MMS, and was strongly impaired in homologous recombinational activity. PMID- 8450309 TI - Chromosome organization of Streptococcus mutans GS-5. AB - Twenty-eight genetic loci have been physically mapped to specific large restriction fragments of the Streptococcus mutans GS-5 chromosome by hybridization with probes of cloned genes or, for transposon-generated amino acid auxotrophs, with probes for Tn916. In addition, restriction fragments generated by one low-frequency-cleavage enzyme were used as probes to identify overlapping fragments generated by other restriction enzymes. The approach allowed construction of a low resolution physical map of the S. mutans GS-5 genome using restriction enzymes ApaI (5'-GGGCC/C), SmaI (5'-CCC/GGG), and NotI (5' GC/GGCCGC). PMID- 8450310 TI - The complete nucleotide sequence of the gene encoding the nontoxic component of Clostridium botulinum type E progenitor toxin. AB - We have analysed the genes borne on a 6.0 kb HindIII fragment cloned from the chromosome of Clostridium botulinum type E strain Mashike. This fragment, cloned within plasmid pU9EMH, contains part of the structural gene for botulinum toxin type E neurotoxin as well as the entire structural gene for a nontoxic component of botulinum type E progenitor neurotoxin gene, ent-120. ent-120 is transcribed in the same direction as the neurotoxin gene and consists of one open reading frame encoding 1162 amino acid residues. Western blotting with anti-nontoxic component sera demonstrates that ent-120 encodes a protein of 120 kDa which forms part of the nontoxic component. ent-120 is homologous to an analogous gene found in botulinum type C strains (69.3% identity at the nucleotide level and 56.1% at the amino acid level). Two stretches of amino acids at the N-terminus of the ent 120 protein are highly homologous to amino acid sequences within the type E neurotoxin. The stop codon of the ent-120 gene is situated 27 nucleotides upstream from the start codon of the neurotoxin gene. PMID- 8450311 TI - Cloning of genes for proline and leucine biosynthesis from Brucella abortus by functional complementation in Escherichia coli. AB - By selecting for growth of Escherichia coli mutant strains in the absence of the required amino acid, clones were found in a Brucella abortus library carrying genes for glutamyl phosphate reductase (proA) and beta-isopropylmalate dehydrogenase (leuB). These clones hybridized to unique fragments in a genomic digest of B. abortus DNA. The proA-complementing DNA was found in a region of 1.3 kb, which directed the synthesis of a protein of 48,000 Da with a pI of 6.3 in maxicells. The leuB-complementing activity was in a region of 1.4 kb and directed synthesis of a protein of 46,000 Da with a pI of 5.9. PMID- 8450312 TI - Immunogold localization of the DnaK heat shock protein in Escherichia coli cells. AB - Previously reported cell fractionation experiments have yielded conflicting information on the cellular localization of the DnaK heat shock protein of Escherichia coli. Here we used immunogold labelling of ultra-thin sections to determine the localization of DnaK in unstressed cells at 30 degrees C as well as in heat-shocked cells. In cells grown at 30 degrees C, gold particles were found predominantly in the cytoplasm, indicating that the majority of the DnaK molecules are cytoplasmic; however, a fraction of the gold particles was located in proximity to the membranes, raising the possibility that a subpopulation of DnaK proteins is membrane-associated. Heat shock of the cells did not induce detectable relocalization of DnaK. PMID- 8450314 TI - Starfish saponins, part 49. New cytotoxic steroidal glycosides from the starfish Fromia monilis. AB - Nine new cytotoxic steroidal glycosides 1-9 have been isolated from the starfish Fromia monilis collected off New Caledonia. Structures of these compounds, which include four mono-(1-4), two di-(5,6), and three glycosides (7-9), were elucidated through spectral interpretation. Monilosides G [7], H [8], and I [9] are the first tri-glycosides to be found among the group of glycosides of polyhydroxilated steroids from starfishes. PMID- 8450313 TI - Developments in marine natural products. Receptor-specific bioactive compounds. AB - The discovery of thousands of new marine natural products over the past two decades has been spurred by findings of potent bioactivity. In recent years it has become apparent that many such compounds have affinities for certain cellular receptors in the mammalian cell, functional properties that may also play a part in the largely unknown roles of these compounds in their respective parent organisms. Our work in marine natural products has led to the discovery of compounds with significant activity in several assays with importance in understanding fundamental cellular processes and treatment of human disease states. We present recent work on the isolation of new bioactive compounds from marine invertebrates with profound activity on mammalian and non-mammalian receptors. PMID- 8450315 TI - New sucrose derivatives from the bark of Securidaca longipedunculata. AB - Two new bitter principles were isolated from the bark of Securidaca longipedunculata (Polygalaceae) and identified as beta-D-(3,4 disinapoyl)fructofuranosyl-alpha-D-(6-sinapoyl)g lucopyranoside and beta-D-(3 sinapoyl)fructofuranosyl-alpha-D-(6-sinapoyl)gluco pyranoside. The structures were elucidated by a combination of 1H nmr (1D, 2D COSY, 2D HOHAHA), 13C-nmr, and fabms spectra. PMID- 8450316 TI - A new antibacterial sesquiterpene from Premna oligotricha. AB - A novel sesquiterpene, 7 alpha-hydroxy-6, 11-cyclofarnes-3(15)-en-2-one [1], has been isolated from the aerial parts of Premna oligotricha (Verbenaceae) using an antimicrobial bioassay-guided isolation procedure. The sesquiterpene was identified on the basis of spectroscopic data and showed weak activity against Gram-positive bacteria Bacillus pumilus, Bacillus subtilis, Staphylococcus aureus, and Streptococcus faecalis. PMID- 8450317 TI - Cytotoxic principles and their derivatives of Formosan Solanum plants. AB - The new steroidal alkaloid capsimine-3-O-beta-D-glucoside [1] was isolated from the root bark of Solanum capsicastrum, and carpesterol [2], 3 beta-(p-hydroxy) benzoyloxy-22 alpha-hydroxy-4 alpha-methyl-5 alpha-stigmast-7-en-6-one [3], and a new steroidal glycoside named indioside A [4] were isolated from the fruit of Solanum indicum. Indioside A was characterized as 3 beta-O-[alpha-L rhamnopyranosyl-(1-->2), beta-D-glucopyranosyl-(1-->4), beta-D-glucopyranosyl-(1- >3)-]alpha-L-rhamnopyranosyl-(-->2)]-beta-D- glucopyranosyl]-diosgenin. Khasianine, dihydrosolasodine, capsimine, and capsimine-3-O-beta-D-glucoside exhibited strong activity against liver damage induced by CCl4. Capsimine and narigenin exhibited significant cytotoxic effect against human PLC/PRF/5 and KB cells in vitro, and capsicastrine and etioline exhibited significant cytotoxicity against human PLC/PRF/5 cells in vitro. PMID- 8450318 TI - Cytotoxic and antimalarial bisbenzylisoquinoline alkaloids from Cyclea barbata. AB - An alkaloid extract derived from the roots of Cyclea barbata demonstrated cytotoxic and antimalarial activities, and five bisbenzylisoquinoline alkaloids, (+)-tetrandrine [1], (-)-limacine [2], (+)-thalrugosine [3], (+)-homoaromoline [4], and (-)-cycleapeltine [5], were isolated as the active principles. The complete and unambiguous assignments of the 1H- and 13C-nmr data of these substances were made by 1D and 2D nmr techniques (COSY, phase-sensitive ROESY, HETCOR, and FLOCK). PMID- 8450319 TI - Cytotoxic and antimalarial bisbenzylisoquinoline alkaloids from Stephania erecta. AB - (+)-2-N-Methyltelobine [1], a new alkaloid, together with twelve known bisbenzylisoquinolines, was isolated from the tubers of Stephania erecta. The structure determination and the complete 1H- and unambiguous 13C-nmr assignments of 1 were obtained through extensive use of several 1D and 2D nmr techniques. All alkaloids inhibited the growth of cultured Plasmodium falciparum strains D-6 and W-2 and displayed nonselective cytotoxicity with a battery of cultured mammalian cells. These data were used for the calculation of selectivity indices. Relative to known antimalarial agents, these bisbenzylisoquinoline alkaloids do not appear to be promising clinical candidates at the present time. PMID- 8450320 TI - Metabolism of safflor yellow B by human intestinal bacteria. PMID- 8450321 TI - Screening of marine invertebrates for the presence of ergosterol-sensitive antifungal compounds. AB - A simple in vitro agar disk diffusion assay has been employed to detect the presence of ergosterol-sensitive antifungal activity in extracts of marine invertebrates. A collection of 116 marine sponges, ascidians, and cnidarians was assayed to reveal 10 samples (8.3%) with significant activity against Candida albicans. The antifungal activities of three of these extracts were unaffected in the presence of increasing concentrations of ergosterol, while another three were significantly reduced by ergosterol. The activity of jaspamide [3], a potent antifungal from the sponge Jaspis sp., was also reduced by ergosterol concentrations as low as 10 ppm. This ergosterol sensitivity is paralleled by the well-known ergosterol dependence of polyene antifungals, such as amphotericin B [1], and suggests a common mode of activity. The assay may be useful in mechanism selective screening for new antifungals and as a dereplication tool. PMID- 8450322 TI - Alepposides, cardenolide oligoglycosides from Adonis aleppica. AB - The structures of novel oligoglycosidic cardenolides, alepposide A (C55H86O23) [1] and alepposide B (C48H74O20) [2], have been deduced mainly by nmr methods. Based on homonuclear (1H and 13C nmr, 1H COSY) and proton-detected heteronuclear shift correlation experiments [HMQC both for 1J(C,H) and for long-range couplings], alepposide A [1] was shown to have the structure strophanthidin-3-O beta-glucopyranosyl-(1-->4)-O-beta-diginopyranosyl -(1-->4)-O - beta oleandropyranosyl-(1-->4)-O-beta-digitoxopyranosyl-(1-- >4)-O-beta- digitoxopyranoside. The structure of alepposide B [2] was established as strophanthidin-3-O-beta-glucopyranosyl-(1-->4)-O-beta-oleandropyranos yl- (1-->4) O-beta-digitoxopyranosyl-(1-->4)-O-beta-digitoxopyranos ide. PMID- 8450323 TI - Kahukuenes, new diterpenoids from the marine alga Laurencia majuscula. AB - Kahukuenes A [4] and B [5], new diterpenoids possessing an unprecedented prenylated chamigrene structure as part of a decalin ring, were isolated from the Hawaiian marine alga Laurencia majuscula. Spectroscopic methods, including extensive 1D and 2D nmr studies, were used to establish the structure and relative stereochemistry of these two secondary metabolites. PMID- 8450324 TI - Biomimetic transformations of parthenolide. AB - An investigation of BF3-mediated rearrangements of parthenolide [1] provided micheliolide [5] as a major product. Minor reaction products included 10 (14) dehydro-5 alpha-hydroxy-trans-guaianolide [2], 9,10-dehydro-5 alpha-hydroxy-trans guaianolide [3], the xanthanolide 2-desoxy-6-epi-parthemollin [4], 1,2-dehydro-4 alpha-hydroxyguaianolide [6], 11,13-dehydrocompressanolide [7], and bicyclo[6.2.0]dec-10(14)-en-12,6-olide [8]. Their mechanisms of formation were interpreted as rearrangements involving carbocation intermediates. PMID- 8450325 TI - Brominated indole alkaloids from the marine tunicate Pseudodistoma arborescens. AB - Chemical investigation of the cytotoxic CH2Cl2-soluble extract of the marine tunicate Pseudodistoma arborescens led to the isolation of four brominated indole alkaloids, arborescidines A [1], B [2], C [3], and D [4], which were characterized by their spectral data, especially 2D nmr. Only arborescidine D [4] showed moderate activity (IC50 3 micrograms/ml) in vitro against the growth of KB human buccal carbinoma cells. PMID- 8450326 TI - A randomized controlled trial of high-dose intravenous nicardipine in aneurysmal subarachnoid hemorrhage. A report of the Cooperative Aneurysm Study. AB - Because of their action as cerebral vasodilators, dihydropyridine calcium antagonists have received intense scrutiny for their potential benefit in ameliorating the devastating consequences of delayed cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH). From October, 1987, to September, 1989, 41 North American neurosurgical centers in the Cooperative Aneurysm Study accrued 906 patients with recent (Days 0 to 7) aneurysmal SAH into a prospective randomized double-blind placebo-controlled trial of high-dose intravenous nicardipine to test whether treatment with this agent improved overall outcome. Eligible patients received 0.15 mg/kg/hr of either nicardipine or placebo by continuous infusion for up to 14 days following hemorrhage. The 449 patients randomly assigned to the nicardipine-treated group and the 457 patients assigned to the placebo-treated group were balanced with regard to prognostic factors for ischemic deficits from vasospasm and for overall outcome. Other medical and surgical interventions were used with similar frequency in both groups, except that antihypertensive agents were used less frequently in the nicardipine-treated patients (26% of the nicardipine-treated group vs. 43% of the placebo-treated group, p < 0.001), and more patients in the placebo-treated group had intentional hypervolemia, induced hypertension, and/or hemodilution administered therapeutically for symptomatic vasospasm (38% of the placebo-treated group vs. 25% of the nicardipine-treated group, p < 0.001). The incidence of symptomatic vasospasm during the treatment period was higher in the placebo-treated group (46%) than in the nicardipine-treated group (32%) (p < 0.001). Despite the reduction in symptomatic vasospasm in the nicardipine-treated group, overall outcome at 3 months was similar between the two groups. Fifty-five percent of nicardipine-treated patients were rated as having a good recovery according to the Glasgow Outcome Scale at follow-up review and 17% were dead, compared to 56% and 18%, respectively, in the placebo-treated group (not statistically significant). These data suggest that high-dose intravenous nicardipine treatment is associated with a reduced incidence of symptomatic vasospasm in patients with recent aneurysmal SAH, but not with an improvement in overall outcome at 3 months when compared to standard management in North America. It is postulated that, while nicardipine prevents vasospasm, hypertensive/hypervolemic therapy may be effective in reversing ischemic deficits from vasospasm once they occur. PMID- 8450327 TI - A randomized trial of nicardipine in subarachnoid hemorrhage: angiographic and transcranial Doppler ultrasound results. A report of the Cooperative Aneurysm Study. AB - Calcium antagonist drugs were proposed for use in patients with recent aneurysmal subarachnoid hemorrhage (SAH) because of their ability to block the effects of a wide variety of vasoconstrictor substances on cerebral arteries in vitro. It was suggested that these agents might, therefore, be useful in ameliorating cerebral vasospasm and its ischemic consequences which frequently complicate SAH. This hypothesis was tested in an arm of a randomized double-blind placebo-controlled trial of high-dose intravenous nicardipine in patients with recently ruptured aneurysms. Participating investigators were required to send selected copies of all admission and follow-up angiograms obtained between Days 7 and 11 following hemorrhage (the peak period of risk for vasospasm) to the Central Registry of the Cooperative Aneurysm Study for blinded interpretation and review for the presence and severity of angiographic vasospasm. In centers with transcranial Doppler ultrasound (TCD) capabilities, middle cerebral artery (MCA) mean flow velocities were measured and recorded. Angiograms obtained between Days 7 and 11 were available for 103 (23%) of 449 patients receiving nicardipine and 121 (26%) of 457 receiving placebo. There was a balance of prognostic factors for vasospasm between the groups. Fifty-one percent of placebo-treated patients had moderate or severe vasospasm on "Day 7-11 angiograms" compared to 33% of nicardipine-treated patients. This difference is statistically significant (p < 0.01). Sixty-seven (49%) of 137 placebo-treated patients examined with TCD between Days 7 and 11 had mean MCA flow velocities exceeding 120 cm/sec compared to 26 (23%) of 112 nicardipine-treated patients (significant difference, p < 0.001). These data suggest that high-dose intravenous nicardipine reduces the incidence and severity of delayed cerebral arterial narrowing in patients following aneurysmal SAH. PMID- 8450328 TI - Management outcome in the elderly patient following subarachnoid hemorrhage. AB - The purpose of this study was to investigate whether the overall management outcome for elderly patients with subarachnoid hemorrhage (SAH), especially for those aged 70 to 79 years, has improved. To this end, the author compared data for the period between 1986 and 1990 (Study Period 2) with those obtained between 1980 and 1985 (Study Period 1). Of 503 patients who were admitted by Day 3 after SAH during the two study periods, 243 (48%) were 59 years of age or younger, 129 (26%) were 60 to 69 years of age, 102 (20%) were 70 to 79 years of age, and 29 (6%) were 80 years of age or older. The percentage of patients aged 70 years or more doubled from 17% during Study Period 1 to 34% during Study Period 2. During Study Period 1, the older patients had a lower operability rate; during Study Period 2, the operability rate for patients aged 70 to 79 years (69%) was similar to that for patients aged 50 to 69 years. At 6 months after SAH for patients aged 70 to 79 years, the overall management and surgical results of good recovery or moderate disability were 18% and 36%, respectively, during Study Period 1, and improved to 41% and 60%, respectively, during Study Period 2. During Study Period 1, the cumulative 5-year survival probabilities for overall management were 58% for patients aged 59 years or less, 53% for those aged 60 to 69 years, and 24% for those aged 70 to 79 years; during Study Period 2, these probabilities improved to 70%, 58%, and 47%, respectively. The 5-year survival rates of surgically treated patients in these three age groups increased from 77%, 68%, and 44% to 88%, 77%, and 69%, respectively. PMID- 8450329 TI - Increased interleukin-6 levels in cerebrospinal fluid following subarachnoid hemorrhage. AB - Serum and cerebrospinal fluid (CSF) samples from 12 patients were analyzed for interleukin (IL)-6, soluble IL-2 receptor (IL-2R), and soluble CD8 levels in order to determine the immune activation profile following subarachnoid hemorrhage (SAH). Dramatically increased levels of IL-6 and moderate increases of soluble IL-2R were detected in the CSF in 11 of the 12 patients; slightly elevated levels of soluble CD8 were observed in six patients. The IL-6 levels were higher on Day 6 than on Days 3 and 9. The increases in IL-6, soluble IL-2R, and soluble CD8 levels in the CSF samples were not paralleled by increased values in the serum samples, and thus probably reflected an intrathecal synthesis of the cytokine. Passive transfer of IL-6 across the blood-brain barrier seemed not to occur since the serum and CSF levels of IL-6 showed a negative correlation. The findings suggest a severe inflammatory affection of the central nervous system that could be of importance in understanding the clinical course in patients following SAH. PMID- 8450330 TI - Tonsillar herniation: the rule rather than the exception after lumboperitoneal shunting in the pediatric population. AB - Although the development of tonsillar herniation (acquired Chiari malformation) in association with lumboperitoneal (LP) shunting is well recognized, it has previously been considered rare. In order to ascertain the incidence of this complication after LP shunting, the authors undertook a retrospective study of all patients in whom this form of shunt had been inserted between 1974 and 1991 at The Hospital for Sick Children, Toronto. In the 143 patients, the mean age at insertion was 3.3 years and the indications for shunt placement were hydrocephalus (81%), pseudotumor cerebri (7%), cerebrospinal fluid fistula (6%), and posterior fossa pseudomeningocele (6%). The mean follow-up period was 5.7 years, during which time there was one shunt-related death due to unsuspected tonsillar herniation. Five other patients developed symptomatic tonsillar herniation treated by suboccipital decompression. Review of all computerized tomography (CT) scans not degraded by artifact showed evidence of excess soft tissue at the level of the foramen magnum in 38 (70%) of 54 patients so studied. In order to confirm that this CT finding represented hindbrain herniation, sagittal and axial magnetic resonance (MR) images were obtained for 17 asymptomatic patients and revealed tonsillar herniation (range 2 to 21 mm) in 12 (70.6%). In addition, some of these asymptomatic patients had evidence of uncal herniation and mesencephalic distortion. Similarities and distinctions are drawn between the morphological changes occurring after LP shunting and those seen in association with the Chiari I and II malformations. Although less than 5% of this study population required treatment for tonsillar herniation, the incidence of this complication was high in asymptomatic patients; MR imaging surveillance for patients with LP shunts is therefore recommended. PMID- 8450331 TI - Progressive myelopathy secondary to odontoid fractures: clinical, radiological, and surgical features. AB - Late-onset progressive myelopathy, years after odontoid fracture, is considered a rarity. Sixteen patients with diagnosis of their odontoid fractures delayed from four months to 45 years have been studied and treated. Three had forgotten about the injury and, in the rest, the significance had been minimized by their clinicians. Fifteen patients had characteristic C-2 nerve root pain and 10 had noted weak hands and walking difficulties. Fifteen patients had Type II fractures, which were mobile in 11; hypertrophic pseudoarthrosis was marked in two. In seven patients it was confirmed at surgery that all or part of the transverse ligament was interposed in the fracture. Transoral surgery, combined with a variety of posterior fusion techniques, has allowed cord decompression, an understanding of the pathomechanics, and sound posterior bone fusion with arrest of the myelopathic condition. Measurements of craniovertebral angles and cord cross-sectional area in this series revealed a rough correlation, but the most striking relationship was between length of delay in diagnosis and diminished cord area in both non-union and malunion, suggesting a progressive injury mechanism. It is proposed that late myelopathy following odontoid fracture may be more common than hitherto believed and should be considered in the evaluation of patients with cervical spondylosis. The condition may be progressive. Finally, non-union may be due to interposition of the transverse ligament. PMID- 8450332 TI - Is polar spongioblastoma a tumor entity? AB - The distribution of cells in a parallel fashion with palisades of nuclei is common in neuroepithelial tumors. The authors have selected 16 such tumors from their series for study, as examples of different neuroepithelial oncotypes containing palisades of nuclei: three ependymomas, three hemispheric pilocytic astrocytomas, three oligodendrogliomas, three medulloblastomas, three cerebellar astrocytomas, and one central neuroblastoma. In two additional tumors, affecting a 12-year-old girl and a 51-year-old woman, this feature was present in the entire surgical specimen and the diagnosis was consistent with a polar spongioblastoma. This diagnosis applies in the literature to rate tumors of childhood and adolescence, both malignant and with embryonal features. In one specimen, a clear ependymomatous feature was found in a remote area of the tumor and in the other there were ultrastructural characteristics of neuroblastoma. Nuclear palisades can be found as local architectural features in many neuroepithelial tumors. The rare tumors diagnosed as polar spongioblastoma, according to published criteria, correspond to ependymomas and neuroblastomas. Polar spongioblastoma does not exist as a tumor entity. PMID- 8450333 TI - Platelet-activating factor and cerebral vasospasm following subarachnoid hemorrhage. AB - This study examines whether platelet-activating factor (PAF) is involved in the occurrence of vasospasm after subarachnoid hemorrhage (SAH). A vasospasm model was produced in rabbits, with animals in six experimental groups receiving two subarachnoid injections of autologous arterial blood with the addition of one of the following; saline (Control Group 1), 25% dimethyl sulfoxide (Control Group 2), PAF (1, 2.5, 5, or 10 micrograms), CV6209 (10 or 100 micrograms), BN52021 (10 or 100 micrograms), or anti-PAF immunoglobulin G (IgG, 50 or 500 micrograms). No significant differences were detected between Control Groups 1 and 2 with regard to neurological deterioration and basilar artery constriction after SAH was induced. Administration of PAF together with autologous blood aggravated neurological deficits in a dose-dependent manner (r = 0.724, p < 0.001) and produced basilar artery constriction at two doses each of 2.5 micrograms (p < 0.05), 5 micrograms (p < 0.01), and 10 micrograms (p < 0.01). Neurological deterioration was prevented in rabbits receiving an intracisternal administration of either PAF antagonist CV6209 or BN52021 or anti-PAF IgG (p < 0.01 at a total dose of 20 micrograms and p < 0.05 at a total dose of 200 micrograms CV6209, p < 0.01 at total doses of 20 and 200 micrograms BN52021, and p < 0.01 at total doses of 100 and 1000 micrograms anti-PAF IgG). A reduction in basilar artery constriction was achieved by the injection of anti-PAF IgG (p < 0.05 at total doses of 100 and 1000 micrograms). Histological examination at autopsy on Days 14 to 21 showed mainly ischemic changes in the brain, including selective neuronal necrosis and cerebral infarction. The control and PAF groups showed marked ischemic changes. On the other hand, no ischemic changes were noted in the anti PAF IgG group, and only 9% of animals in the CV6209 group and 25% in the BN52021 group demonstrated selective neuronal necrosis or infarction. This study thus provides evidence to support the role of PAF in the pathogenesis of vasospasm after SAH. PMID- 8450334 TI - The expression of deafferentation dysesthesias reduced by dorsal root entry zone lesions in the rat. AB - Extensive longitudinal lesions of the dorsal root entry zone (DREZ) are effective in relieving some chronic deafferentation pain in humans. A deafferentation syndrome follows C5-T2 dorsal root ganglionectomies in rats. The syndrome consists of biting and scratching the completely and partially denervated limb areas, respectively. This study examines the effect of DREZ lesions on the deafferentation syndrome in the rat. Of 37 rats, 24 underwent C5-T2 ganglionectomies only, five received C4-T3 micromechanical DREZ lesions only, and eight underwent ganglionectomies plus simultaneous DREZ lesions. The animals were observed for 45 days post-operatively. Histological analysis of the spinal cord lesions was performed. All rats with ganglionectomies alone exhibited the deafferentation syndrome; however, no rats with DREZ lesions alone showed this feature. Only 25% of rats with combined ganglionectomies and DREZ lesions exhibited the deafferentation syndrome in the first 30 days, whereas 80% of the animals with ganglionectomies only did so. Although 75% of the animals with combined lesions eventually bit the insensitive forepaw, this behavior was significantly attenuated: the day of onset was delayed and the extent of self mutilation was reduced. Postmortem histological examination of the DREZ lesions indicated a close association between the completeness of the dorsal horn destruction and the reduction or prevention of self-mutilation. These data support the validity of the animal model and also the hypothesis stating that the deafferentation syndrome results from abnormal spontaneous neural activity in the dorsal horn. Moreover, the variability of the histological findings in these experiments stresses the importance of making contiguous and complete dorsal horn lesions in human DREZ surgery. PMID- 8450335 TI - Thienylphencyclidine protection for the spinal cord of adult rats against extension of lesions secondary to a photochemical injury. AB - The purpose of this study was to evaluate treatment with the N-methyl-D-aspartate antagonist thienyl-phencyclidine (TCP) after spinal cord injury for its behavioral, electrophysiological, morphological, and immunohistochemical effects. Five minutes after a photochemical lesion was produced in rats at the T-8 level, the animals received TCP (1 mg/kg, intravenously) or TCP vehicle (saline). The animals were evaluated on Day 18 for neurological recovery by testing motor and sensory functions. The TCP-treated group showed less neurological impairment than the untreated group (p < 0.05 for inclined-plane stability and withdrawal reflex to extension). Somatosensory evoked potential testing was performed on Days 21 to 23 and the wave amplitude between the onset and P1 in the TCP-treated group was higher than in the untreated group (p < 0.05). Mean arterial blood pressure was not significantly modified after TCP injection. Morphometric studies of the lesion area in cross section revealed a significantly reduced spinal cord infarction in the TCP-treated group (p < 0.05). Immunohistochemical evaluation of the spinal cord in lumbar area showed an increased level of serotonin immunoreactivity in the dorsal horn of animals treated by TCP. These results demonstrate the efficacy of TCP in reducing secondary lesions after spinal cord injury in rats. PMID- 8450336 TI - Role of histocompatibility antigen gene and protooncogene expressions in intracerebral tumorigenicity of mouse neuroblastoma. AB - The role of N-myc, c-src, and major histocompatibility complex (MHC, H-2 in the mouse) class I antigen gene expressions in dimethyl sulfoxide (DMSO)-induced differentiation and intracerebral tumorigenicity was examined using a mouse MNB85 neuroblastoma cell line. A fluorescence-activated cell sorter disclosed cell surface MHC enhancement by DMSO, causing an increase in cytotoxic T-lymphocyte sensitivity. Southern blot analysis verified a single copy of the proto-oncogenes and MHC deoxyribonucleic acids in both untreated and DMSO-treated MNB85 cells. Northern blot analysis indicated that DMSO treatment induced a decrease in N-myc and an increase in c-src and MHC messenger ribonucleic acids. Nuclear run-off transcription assay revealed down-regulation of N-myc at a posttranscriptional level, contrasted with primary up-regulation of c-src at a transcriptional level. Immunoprecipitation after treatment with enzyme endo-beta-N-acetyl-glycoseamidase H proved that the terminal glycosylation of MHC heavy-chain gene products normally occurs in the Golgi apparatus of MNB85 cells. Intracerebral tumorigenicity assay showed that cells highly MHC-expressed by DMSO were less tumorigenic than untreated cells in association with DMSO-augmented cytotoxic T lymphocyte susceptibility. These results suggest that proto-oncogenes may be linked to cellular differentiation, while cell-surface MHC gene expression influences intracerebral immunosurveillance. PMID- 8450337 TI - T-cell receptor V-gene usage in neoplasms of the central nervous system. A comparative analysis in cultured tumor infiltrating and peripheral blood T cells. AB - The use of tumor-infiltrating lymphocytes in the treatment of central nervous system (CNS) neoplasms has met with serious obstacles due to difficulty of culture and poor characterization. Since in other tumors the therapeutic effects of tumor-infiltrating lymphocytes have been shown to rely on T-cell receptor engagement, the authors addressed the question as to whether expression of T-cell receptor variable (V) domains in cultured tumor-infiltrating lymphocytes from CNS is different from that of autologous cultured peripheral blood mononuclear cells. Infiltrating lymphocytes from CNS neoplasms, including primary malignancies, metastatic cancers, and meningiomas, were cultured in the presence of interleukin 2 and anti-CD3 monoclonal antibodies (MoAb's) in order to obtain optimum growth of T cells. Autologous peripheral blood mononuclear cells from the same patients were similarly cultured. After 4 to 5 weeks of culture, 97.3% +/- 2.6% (mean +/- standard deviation) of the resulting cell populations were CD3-positive lymphocytes. The expression of T-cell receptor V domains was then studied by using a panel of 12 MoAb recognizing gene products from T-cell receptor V-alpha 2, V-beta 5, 6, 8, and 12, V-gamma 4 and 9 families, and from two subfamilies of V-delta 2. Remarkably, in over 70% of all paired measurements, percentages of T cells expressing discrete T-cell receptor V-gene products were found to be virtually identical in tumor- and peripheral blood-derived cultured cell populations, with differences never exceeding 1%. In contrast, a different expression of individual V-gene products, concerning both alpha/beta and gamma/delta T-cell receptors, could be detected between cultured tumor infiltrating lymphocytes and autologous peripheral blood-derived T lymphocytes in seven of 12 patients. In two cases, significant differences between the two populations were also observed in the proliferative responses obtained upon stimulation with staphylococcal enterotoxins that trigger defined V-beta T-cell receptors. Altogether, these data suggest that the T-cell receptor repertoire of cultured tumor-infiltrating lymphocytes from CNS tumors, suitable for use in adoptive immunotherapies, differs from that of autologous cultured peripheral blood mononuclear cells. PMID- 8450338 TI - LINAC radiosurgery: an animal model. AB - Fifteen cats were irradiated with an animal LINAC (linear accelerator) radiosurgery device. After 6 months, they were studied with gadolinium-enhanced magnetic resonance (MR) imaging, gross pathology after Evans blue perfusion, and histopathology. The lesion size was relatively constant in the cats receiving a dose of 7500, 10,000, 12,500, or 15,000 cGy to the 84% isodose line of a 1-cm collimator. The composition of the lesion correlated with dose: the lower-dose lesions were found histologically to contain areas of edema, demyelination, reactive gliosis, and vascular proliferation; the higher-dose lesions contained increasing amounts of hemorrhage and coagulative necrosis. The borders of the lesions were sharply demarcated from surrounding normal brain. Gadolinium enhanced MR studies correlated well with areas of blood-brain barrier breakdown, as confirmed by areas of Evans blue staining. This model could serve as the basis for further studies of the biological effects of LINAC radiosurgery. PMID- 8450339 TI - The radiobiology of human acoustic schwannoma xenografts after stereotactic radiosurgery evaluated in the subrenal capsule of athymic mice. AB - An experimental model with xenograft transplantation into the subrenal capsule of athymic (nude) mice was used to evaluate the early response of human acoustic schwannomas to stereotactic radiosurgery. After xenograft placement, 45 mice underwent radiosurgery with single doses of 10, 20, or 40 Gy using a 201-source 60Co gamma unit (4-mm collimator, single isocenter, 80% isodose line). The 45 radiosurgery-treated xenografts were compared with 15 untreated xenografts and 15 xenografts in mice that underwent "sham radiosurgery." All five study groups were matched for the following pretreatment variables: patient of origin, animal weight, average xenograft diameter, and percentage of xenograft surface vascularity. Immediately prior to sacrifice of the mice all xenografts were evaluated in situ to determine the average tumor diameter, tumor volume, and percentage of surface vascularity. Mice were sacrificed 2 weeks, 1 month, or 3 months after radiosurgery. Blinded histological review was performed by an independent neuropathologist. Tumor volume was reduced 33.6% after 2 weeks (p = 0.023) and 45% after 3 months (p = 0.018) in the 40-Gy radiosurgery group. Tumor volume was reduced by 46.2% after 1 month (p = 0.0002) and 35.2% after 3 months (p = 0.032) in the 20-Gy radiosurgery group. An average volume reduction of 16.4% was observed after 3 months (p = 0.17) in the 10-Gy radiosurgery group. At 3 months after surgery, tumor surface vascularity was reduced by an average of 19.7% (p = 0.043) in the 40-Gy radiosurgery group and 5.8% (p = 0.12) in the 20 Gy radiosurgery group and was unchanged in the 10-Gy radiosurgery group and both control groups. Histological examination demonstrated a higher incidence of hemosiderin deposits (p = 0.026) and vascular mural hyalinization (p = 0.032) in radiosurgery xenografts versus control. The subrenal capsule xenograft in nude mice was an excellent model for studying the in vivo radiobiology of acoustic schwannomas after radiosurgery. Both cellular and vascular effects could be assessed serially in situ and the model was stable even 4 months after transplantation. Additional studies investigating radiobiology over periods better approximating the time course of clinical neuroimaging changes (6 to 12 months) are warranted. PMID- 8450340 TI - Neuronal heterotopia with capillary penetration of neurons and cortical dysplasia in a patient with complex partial seizures. Case report. AB - Unusual pathological findings were encountered in a temporal lobectomy specimen from a 9-year-old boy with intractable complex partial seizures. Magnetic resonance imaging revealed an enlarged left temporal lobe, with diffuse high signal intensity over the cortex and poor gray-white differentiation on T2 weighted imaging; single-photon emission computerized tomography showed decreased blood flow. Active epileptiform discharges were identified in the left temporal lobe with focal slow waves and generalized epileptiform paroxysms. Pathologically, the cortex revealed changes of focal cortical dysplasia with extensive disorganization of neuronal morphology, layering, and orientation as well as focal polymicrogyria. The cortical-white matter junction was indistinct with extensive neuronal heterotopias in the white matter. Large pale balloon cells akin to those seen in tuberous sclerosis were found scattered within the cortex and white matter. The most striking finding was that of a heterotopic nodule in the white matter, which revealed abnormal neurons with penetration of cell bodies by capillaries. Ultrastructurally, there were no degenerative changes in these neurons, and this unusual phenomenon is attributed to a developmental disturbance affecting neuronal, glial, and vascular elements. PMID- 8450341 TI - Epidural migration of hemostatic agents as a cause of postthoracotomy paraplegia. Report of two cases. AB - Paraplegia secondary to pulmonary surgery occurred in two patients because of epidural migration of hemostatic agents. Computerized tomography following myelography revealed the lesion clearly. Both patients achieved satisfactory neurological recovery through prompt diagnosis and treatment. PMID- 8450342 TI - Selective endovascular techniques in the treatment of cerebral mycotic aneurysms. Report of three cases. AB - The aim of this study was to evaluate the role of endovascular treatment for intracranial mycotic aneurysms. The clinical and angiographic features of three patients with endocarditic vegetation (two with Streptococcus viridans and one with Staphylococcus) were reviewed retrospectively. Patients were selected for this treatment according to the clinical setting and aneurysm location. In two cases, selective catheterization of a distal middle cerebral and posterior cerebral artery branch with a microcatheter followed by superselective amobarbital testing of the parent vessel was preliminary to the occlusion of that vessel with autologous clot or glue. The third patient was treated by selective occlusion of the aneurysm by intra-aneurysmal placement of platinum minicoils. Two patients presented with intracranial hemorrhage and in one the lesion was found on computerized tomography. All three aneurysms had been excluded from the circulation at the 6-month follow-up review. The only complication from the procedure, despite the septic nature and distal localization, was balloon deflation in one patient, who was successfully retreated with coils. Endovascular embolization is indicated in patients who are at risk of hemorrhage and cannot undergo the standard procedure. The superselective amobarbital test allows selection of patients who will tolerate distal vessel occlusion. This endovascular procedure represents a safe and effective treatment for these lesions. PMID- 8450344 TI - Compression of the C-2 root by a rare anomalous ectatic vertebral artery. Case report. AB - The authors report a symptomatic congenitally anomalous ectatic vertebral artery not passing through the transverse foramen of the atlas (C-1), but instead piercing the dura mater below the posterior arch of the C-1 in the atlantoaxial (C1-2) interlaminar space. This occurrence is exceptionally rare, but in this case it was uniquely associated with occipital neuralgia due to vascular compression of the C-2 root. Microvascular decompression was curative. Neuroradiological and surgical findings are presented and their implications discussed. PMID- 8450343 TI - Intraventricular fat from a ruptured sacral dermoid cyst: clinical, radiographic, and pathological correlation. Case report. AB - The authors report a unique case of a dermoid cyst that ruptured into the lumbosacral subarachnoid space following trauma, resulting in dissemination of cyst contents into the ventricles and cerebrospinal subarachnoid spaces. An intraspinous source should be considered when intraventricular fat is identified without a clear intracranial source. PMID- 8450345 TI - The mandibular swing-transcervical approach to the skull base: anatomical study. Technical note. AB - This report describes in a stepwise fashion the surgical anatomy of an approach to the midline and lateral compartments of the skull base (clivus, infralabyrinthine/infratemporal regions). The salient features of this procedure are represented by a mandibulotomy and by detachment of the pharynx from the skull base through a combined oral and cervical approach. There is full neurovascular control of the internal carotid artery and lower cranial nerves with the possibility of complete exposure of the intrapetrous and intracavernous segments of the internal carotid artery on the side of the exposure. This approach, which may be regarded as an expansion of the original work of Krespi, should be considered when dealing aggressively with extensive skull-base lesions invading the midline and lateral compartments of the skull base. PMID- 8450346 TI - Lund University and its neurobiological traditions. AB - Lund University was founded in 1666 as part of a strategy to assimilate the province of Scania in southern Sweden, which had been obtained from Denmark after a war ending in 1658. The present main building was erected in 1882. The University Hospital and the medical departments are located in the campus area northeast of the building. The main strength of the medical faculty lies in the neuro-biosciences. In retrospect, they offer a fascinating development with interesting historical connections as well as present-day contracts between many scientific disciplines. This shows once again that real scientific progress requires the interaction of many brains; in other words, the cross-fertilization offered by a critically large mass of scientists from different fields working relatively close together over long periods of time. PMID- 8450347 TI - Hyperbaric oxygen for brain injury. PMID- 8450348 TI - Suction control of ultrasonic aspirators. PMID- 8450349 TI - General anesthesia: dentistry's contribution to mankind. PMID- 8450350 TI - Treatment outcomes for temporomandibular joint reconstruction after Proplast Teflon implant failure. AB - A retrospective study of 107 patients (male, n = 13; female, n = 94) with 163 joints previously treated with Proplast-Teflon (PT; Vitek, Inc, Houston, TX) implants was performed. The average time in situ for the PT was 59.8 months (range, 2 to 126 months). Average length of follow-up was 84.6 months (range, 59 to 126 months). Only 12% of joints showed no significant osseous changes radiographically. Forty-five patients (42%) continue to have in situ PT implants and 36% of them experience pain that requires medication; 25% have developed an anterior open bite and malocclusion; 9% have limited vertical opening; and 40% are asymptomatic. Temporomandibular joint (TMJ) reconstruction after PT implant failure was performed with five different autologous tissues or a total joint prosthesis. Autologous tissues used to reconstruct the TMJ and the rates of success were as follows: 1) 31% free temporalis fascia and muscle graft with and 13% without sagittal split ramus osteotomy, 2) 8% dermis, 3) 25% conchal cartilage, 4) 12% costochondral grafts, and 5) 21% sternoclavicular grafts. The success rate decreased in all autologous tissue groups as the number of TMJ surgeries performed before reconstruction increased. Ankylosis was the most common cause of failure. Results of TMJ reconstruction with a total joint prosthesis were as follows: 1) 88% functional and occlusal stability of total joint prosthesis; 2) level of pain reduction was rated as 46% good, 38% fair, and 16% poor; and 3) an average interincisal opening of 27 mm at 24 months or less, and 33 mm at 25 months and beyond.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450351 TI - A comparison of surgical and prosthetic treatment for speech disorders attributable to surgically acquired soft palate defects. AB - Surgical and prosthetic treatments for speech disorders attributable to surgically acquired soft palate defects were investigated. Ten patients who had undergone soft palate resection for extensive cancer served as the subjects. In four patients, the resected portion of the soft palate was confined to the anterior or middle segments, with an intact posterior band, whereas in the remaining six patients the resected portion extended into the posterior edge. An obturator with or without a speech appliance was adapted to all patients in the former group and to one patient in the latter group. The remaining five patients in the latter group underwent surgical reconstruction using a free radial forearm flap immediately after resection of the soft palate. The speech of each patient was evaluated either before and after surgery in those treated only surgically or with and without the obturator in the other patients using a standard intelligibility test of 100 Japanese syllables. These tests showed that two of the four patients with a posterior band of soft palate remaining postsurgically achieved excellent restoration of speech and improvement of velopharyngeal function following placement of a special prosthesis. The patients who had resection extending into the posterior edge of the soft palate obtained better restoration of speech and function from surgical reconstruction rather than prosthetic management. All three patients who had surgical reconstruction, in whom the special obturator was applied achieved a slight increase in speech intelligibility scores resulting from the improvement of velopharyngeal function. These results suggest that surgical reconstruction and prosthetic management may best be applied selectively based on the extent of resection of the soft palate. PMID- 8450352 TI - Skeletal stability following miniplate fixation after bilateral sagittal split osteotomy for mandibular advancement. AB - Skeletal stability after monocortical miniplate fixation of bilateral sagittal split osteotomies to advance the mandible was evaluated in 20 patients. Three angles and four linear measurements were analyzed on lateral cephalometric radiographs before surgery, immediately after surgery, and at least 6 months after surgery. The mean horizontal advancement at pogonion was 5.0 mm; 6 months after surgery the advancement increased 0.3 mm because of occlusal settling. The mean lengthening of the distance gonion to menton was 5.8 mm and a relapse of 0.3 mm (5.2%) was found. The mean increase of anterior facial height measured at long term follow-up was 3.6 mm. This study shows that fixation of the advanced mandible with intraorally applied monocortical miniplates after the bilateral sagittal split osteotomy is a stable procedure. PMID- 8450353 TI - Reactivated herpes simplex virus infection as a possible cause of dry socket after tooth extraction. AB - This study was designed to evaluate a possible association between reactivated herpes simplex virus type 1 (HSV-1) infection after lower third molar extraction and development of dry socket (DS). The HSV-1 antibody response was analyzed before and after tooth removal by enzyme-linked immunosorbent assay and immunoblotting in 208 patients. History of previous possible oral herpes reactivation was evaluated by a questionnaire that was based on self-rated frequency of oral cold sores. Tobacco users were identified. The anatomic proximity of the root apex to the mandibular nerve canal was classified radiographically before extraction. Fifteen patients (7%) developed DS after tooth extraction. Eleven of the 15 DS patients (73%) were HSV seropositive as compared with 7 of 15 (47%) in the matched control group. Seven of the 11 seropositive DS patients have shown HSV-1 reactivation by an increase of specific polypeptides, predominantly gB, gC, gD and ICP 4 and 6, in the immunoblot test. No change in HSV-1 reactivity was observed in control sera. DS patients reported a high frequency of oral cold sores (64%) compared with the controls (33%). Tobacco use was not found to influence the frequency of cold sores or the development of DS. A close radiographic proximity between the mandibular canal and root apex was more common (P < .05) in DS patients. The results indicate that extraction of a mandibular third molar could be a possible cause of reactivation and recurrence of an HSV-1 infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450354 TI - Use of the carbon dioxide laser to locate small sialoliths. AB - Six cases of small salivary duct sialoliths were treated using the carbon dioxide laser as a surgical dissector. When the laser beam encountered the small sialolith (3 mm or less), a light-scattering effect (flash or burst) was observed, thus enabling an almost immediate localization of the stone in the salivary duct or in the surrounding tissue. Stone extirpation is more rapid, with less surgical trauma, using this technique. PMID- 8450355 TI - Complications of nonrigid fixation of mandibular angle fractures. AB - This retrospective study analyzed complications in 96 patients with 99 mandibular angle fractures treated during a 3-year period with either closed reduction or nonrigid means of fixation combined with maxillomandibular fixation. An overall complication rate of 17% occurred. Infection was the most common complication, occurring in 17 fractures. Thirteen fractures had infection as the only complication; in the remaining four patients, infection was combined with malunion/malocclusion. The results of this study show that mandibular angle fractures in an inner-city population are associated with a high incidence of postsurgical complications. PMID- 8450356 TI - The effects of surgical-orthodontic correction of skeletal class III malocclusion on mandibular movement. AB - The effects of surgical-orthodontic treatment on mandibular movement were studied using the mandibular kinesiograph in 30 patients with skeletal class III malocclusion that was corrected by the sagittal split osteotomy (27 patients), a combination of the sagittal split osteotomy and body ostectomy (2 patients), or the sagittal split osteotomy and a posterior alveolar osteotomy of the maxilla (1 patient). Postoperatively, the mean maximum anterior and posterior excursions of the mandible increased significantly from 4.1 to 6.7 mm and from 0.6 to 2.6 mm, respectively. The lateral excursion to the right and left sides also showed significant increases from 4.8 to 7 mm and from 5.5 to 7 mm, respectively, after surgery. In analysis of the habitual and rapid opening and closing movements of the mandible, marked impairment was not observed in most patients except for crossing and discrepancy in the tracings of the habitual opening and closing movements in the sagittal plane observed in 11 patients. These findings were observed in only one patient postoperatively. The results indicate that the surgical orthodontic correction of skeletal class III malocclusion has favorable effects on the function of the mandible. PMID- 8450357 TI - The relationships between the temporomandibular joint disc and related masticatory muscles in humans. AB - A study of the relationships of the temporomandibular joint disc and the lateral pterygoid, temporalis, and masseter muscles during the human fetal period and in the adult was conducted. The superior head of the lateral pterygoid muscle was seen to insert into the anteromedial two thirds of the temporomandibular joint disc. The fibers of the posterior one third of the temporalis muscle and fibers of the deep bundle of the masseter muscle were attached on the anterolateral one third of the disc. The attachment of these muscles to the disc was through the anterior extension of the disc, also known as the premeniscal or prediscal lamina. The possible functional role of these muscle attachments is discussed. PMID- 8450358 TI - Flow cytometric analysis of squamous cell carcinomas of the oral cavity in relation to lymph node metastasis. AB - Nuclear DNA content and cell kinetics were studied in 40 squamous cell carcinomas of the oral cavity by flow cytometry to evaluate the diagnostic significance of the method in predicting lymph node metastasis. The presence of lymph node metastasis was confirmed histologically in 20 carcinomas. The incidence of metastasis was 36% in group A (22 carcinomas of the tongue and floor of the mouth) and 67% in group B (18 carcinomas of the alveolus and gingiva). On flow cytometric analysis, DNA aneuploidy was observed in 23 tumors (58%). The incidence of lymph node metastasis in the aneuploid tumors was 70%, which was significantly higher than the 24% for the diploid tumors. This also was the case for both of the subgroups. The incidence of aneuploidy and the DNA index for tumors with metastasis were 80% and 1.58, respectively. These values were significantly higher than the 35% and 1.16 for tumors without metastasis, but there were no significant differences in the S phase and G2M phase fractions between the tumors with and without metastasis. The incidence of aneuploidy in tumors with metastasis was also higher in group A (75% versus 36%) and group B (83% versus 33%). In terms of histologic differentiation, the incidence of metastasis and aneuploidy increased as the degree of differentiation decreased. Similar relationships were found between the histologic grade of malignancy and the incidence of metastasis and aneuploidy. The results indicate that nuclear DNA content analysis by flow cytometry is useful as a supplement to clinical and histologic evaluation in predicting the tendency of squamous cell carcinomas of the oral cavity to metastasize to regional lymph nodes. PMID- 8450359 TI - The adult respiratory distress syndrome: a review. AB - The adult respiratory distress syndrome, characterized by hypoxemia, reduced pulmonary expansion, and noncardiogenic pulmonary edema, is a clinical entity with a high mortality rate that has been recognized only relatively recently. We present the newest aspects of the subject. PMID- 8450361 TI - Management of an orthognathic surgery patient with factor XI deficiency: review and case report. PMID- 8450360 TI - Update on the vitek partial and total temporomandibular joint systems. AB - A retrospective recall study was done on 262 VK I (N = 138) and VK II (N = 124) (Vitek, Inc, Houston, TX) partial and total temporomandibular joints placed between 1982 and 1990. The cumulative success rate of VK I total joints observed for up to 10 years was approximately 20%, whereas the success rate of VK II total joints observed up to 6 years was approximately 80%. At the 5- to 6-year interval for each, these rates were 44% and 79%, respectively. Wear of the Teflon fluorinated ethylene propylene polymer surface was the primary reason for VK I failure; there was no material failure of the VK II prostheses. Slightly better pain relief, increase in interincisal opening, improvement in diet, and greater overall satisfaction were noted with the use of VK II. A highly significant improvement in success data was found if no surgery had been performed before either VK I or VK II total joint placement. Rib grafts were not particularly helpful after removal of total joint prostheses, particularly if the patient had a history of multiple surgeries. Total temporomandibular joint surgery must be reserved for patients in whom alternative surgical methods have failed or are no longer indicated. All total joint implants, particularly the VK I, must be observed closely with clinical examination and imaging and removed at the earliest sign of material failure. PMID- 8450362 TI - Non-Hodgkin's lymphoma of the lip: a case report. PMID- 8450363 TI - Nasal osteoma: a case report. PMID- 8450364 TI - Giant hemangioma of the parotid gland associated with Kasabach-Merritt syndrome: a case report. PMID- 8450365 TI - Invasive (malignant) external otitis progressing to osteomyelitis of the temporomandibular joint: a case report. PMID- 8450366 TI - Verruciform xanthoma involving the lip: a case report. PMID- 8450367 TI - Use of a skeletal distraction device to widen the mandible: a case report. PMID- 8450368 TI - Reconstruction of large defects that include the mandible with scapular osteocutaneous and forearm flaps: report of cases. PMID- 8450369 TI - The use of tobramycin-impregnated polymethylmethacrylate beads in the treatment of osteomyelitis of the mandible: report of three cases. PMID- 8450370 TI - A landmark for facial nerve identification during parotid surgery. PMID- 8450371 TI - A simple heat pack for oral and maxillofacial applications. PMID- 8450372 TI - Problems with the use of HBO: a matter of opinion. PMID- 8450373 TI - Genetics, immunology, and biliary atresia: an opening or a diversion? PMID- 8450374 TI - Association between HLA and extrahepatic biliary atresia. AB - The etiopathogenesis of extrahepatic biliary atresia (EHBA) remains undefined. There are clinical and pathological suggestions supporting the idea that EHBA could consist of at least two forms: the congenital (embryonic or fetal) and the acquired (perinatal) types. To test the hypothesis that susceptibility to this disease would be influenced by host genetic factors, we studied the human leukocyte antigen (HLA) system in 55 patients with and without major extrahepatic congenital anomalies. We found, especially in those without associated malformations, a significantly higher frequency of HLA-B12, of haplotypes A9-B5 and A28-B35, and of their disequilibrium values, as compared with the 8th International Histocompatibility Workshop controls. This study suggests that immunogenetic factors may play a role in determining susceptibility to EHBA, and the different HLA frequencies in those with and without anomalies lend support to the hypothesis that biliary atresia may be an etiologically heterogeneous disorder. PMID- 8450375 TI - Dr. Apley meets Helicobacter pylori. PMID- 8450376 TI - Helicobacter pylori infection in children: potential clues to pathogenesis. AB - Children (227) undergoing endoscopy for upper gastrointestinal symptoms were investigated for the presence of Helicobacter pylori infection. The histological response to H. pylori infection and the presence of antral nodularity and peptic ulceration were noted. Symptomatic adults (258) undergoing endoscopy were also investigated for the presence of nodularity. H. pylori infection was detected histologically in 32 of 227 (14.1%) children. Of those children infected with H. pylori, half (50%) had antral nodular gastritis. Of 139 H. pylori-positive adults 22 (15.8%) showed nodularity. The active component of the histological response was found to be minimal or lacking in the majority of children infected with H. pylori. Twelve of the 227 children (5.3%) had peptic ulcer disease. Of these, nine were duodenal and three gastric ulcers. Of the nine children with duodenal ulceration three (33%) were infected with H. pylori. As a result of this study we conclude that (a) although antral nodularity occurs more frequently in children it is not exclusive to childhood, (b) the polymorphonuclear response in children is less than that reported in adults, and (c) peptic ulcer disease is rare in children and the present study would suggest that in children it is less frequently associated with H. pylori infection than in adults. PMID- 8450377 TI - Helicobacter pylori-associated gastritis in Kuwait: endoscopy-based study in symptomatic and asymptomatic children. AB - Information is limited concerning the prevalence of Helicobacter pylori infection in asymptomatic children. Since January 1989, we have endoscoped 60 children for recurrent abdominal pain or for obtaining small-intestinal biopsy (their ages were a mean of 6.6 (range 9 months-13 years); there were 37 boys and 23 girls. Antral biopsies were obtained from all subjects and these were studied for the presence of gastritis and stained for H. pylori using modified Gram's stain. All biopsies were cultured for H. pylori. Children endoscoped for small-intestinal biopsy (n = 18) were used for comparison. Of the 42 children who had abdominal pain, 24 showed histological gastritis and 13 had H. pylori on microscopy (31% H. pylori-associated gastritis). In the compared group, five showed histological gastritis, and all had H. pylori on microscopy (27.7%). Culture was positive in 15; sensitivity was 85.7%. Six children, three pairs of siblings, had H. pylori gastritis supporting environmental etiology. Two had coinfection with intestinal giardiasis. Seven children were treated with daily oral amoxycillin (50 mg/kg) and tinidazole (20 mg/kg) for 6 weeks. In 3 (42.3%) H. pylori colonization cleared with healing of gastritis and resolution of symptoms. These results indicate that H. pylori gastritis is equally prevalent in symptomatic and asymptomatic children (31 and 27.7%, respectively; p > 0.05) in our population. It seems that the combination of oral amoxycillin and tinidazole is a poor choice in the treatment of H. pylori-associated gastritis in Kuwaiti children. PMID- 8450378 TI - Postnatal growth in infants born between 700 and 1,500 g. AB - Our purpose was to examine postnatal growth in very low birth weight (VLBW) infants (n = 54). A high frequency of intrauterine growth retardation was noted that was corrected by plotting birth weight against crown-heel length and not gestational age. No differences in postnatal growth were noted between infants whose size was appropriate for gestational age (n = 37) and those small for gestational age (n = 17). Overall, growth tended to exceed that previously published. Weight but not length or head gain was less in the smaller (< or = 1,000 g) when compared to the larger (> 1,000 g) VLBW infant. Poorer weight gain could not be related to more "illness" or less nutrient intake in the smaller infants. PMID- 8450379 TI - Measured resting energy expenditure in children. AB - The majority of equations used to predict values for basal metabolic rates (BMRs) are the result of indirect calorimetry measurements performed in the 1930s and 1950s. To assess the reliability of these equations in predicting the resting energy expenditure (REE) of the children in our community, indirect calorimetry was performed on 92 male and 107 female healthy children 2-3 h postprandial. Each individual was measured for a duration of 15-20 min. The data for analysis were obtained from 5-15 min steady-state periods. Subjects ranged in age from 5 to 16 years. The results were compared with BMRs calculated from the Harris-Benedict equation (Harris J, Benedict F. A biometric study of basal metabolism in man. Washington, DC: Carnegie Institute of Washington, publication no. 279, 1919.), the Food and Agriculture Organization/World Health Organization/United Nations University (FAO/WHO/UNU) equations, and the equations proposed by Schofield for use by the 1985 FAO/WHO/UNU Nutrition Committee. The values predicted by the FAO/WHO/UNU and Schofield equations were consistent with the measured resting values for all the children in the study population. Ninety-two children weighed between 90-110% of their ideal body weight. When the measured REE and estimated BMR were compared by gender and age in these children, the Schofield equations provided the best estimates. Ninety-four of the study subjects weighed > 110% of their ideal body weight. The predicted estimates by all equations were consistent with the measured values in this subgroup of the population. We conclude that the FAO/WHO/UNU and Schofield equations are reliable estimates of metabolic rate in healthy children when measurement of REE is not possible. PMID- 8450380 TI - Plasma amino acid response to ingestion of L-amino acids and whole protein. AB - The effect of whole protein and L-amino acid ingestion on plasma amino acid concentrations was investigated in 10 men. Each subject ingested equivalent amounts of amino acids as cottage cheese (session 1), an L-amino acid mixture (session 2), and cottage cheese and L-amino acids (session 3). Postprandial changes from baseline were larger for essential versus nonessential amino acids in each session. Higher and more rapid rises followed by more rapid declines in individual plasma amino acid concentrations were observed after ingestion of L amino acids alone or with whole protein than after ingestion of an equivalent amount of amino acids as whole protein. Individuals receiving the majority of their essential amino acid and nitrogen needs from elemental products may need, for example, to consume them more frequently or after consumption of other foods in an effort to slow down absorption rates. PMID- 8450381 TI - Iron nutrition and growth of breast- and formula-fed infants during the first 9 months of life. AB - Feeding of iron (Fe)-fortified (12-15 mg/L) infant formulas is an effective and convenient means to protect infants from Fe deficiency. To study lower levels of Fe fortification of infant formulas (3 or 6 mg/L) compared with those currently in use, we compared Fe intake and Fe nutritional status of three groups of healthy, term infants between 90 and 274 days of age. One group received an Fe fortified whey-predominant formula (3 mg/L) and the second group received the same formula with a higher Fe level (6 mg/L). A comparison group was breast-fed at least until 274 days of age. All infants received infant foods and cereals according to European Community recommendations. Mean Fe intake of infants fed formula fortified with 3 mg/L was significantly lower at 183 and 274 days of age (p < 0.05) than that of infants fed formula fortified with 6 mg/L. None of the infants fed the formula fortified with 3 mg/L met the recommended daily allowance value (10 mg) for infants between 6 and 12 months of age. Hemoglobin, hematocrit, mean corpuscular volume, free erythrocyte protoporphyrin, and serum ferritin levels were similar in the formula-fed groups; none of the infants had depleted Fe stores (ferritin < 10 micrograms/L) at 183 and 274 days of age. Thirteen percent of breast-fed infants had depleted Fe stores at 183 days of age, but only 3% were depleted at 273 days of age, when Fe-fortified beikost was already part of the diet. No influence of Fe nutritional status was found on zinc and copper nutritional status or on growth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450382 TI - A morphological study of beta-lactoglobulin absorption by cultured explants of the human duodenal mucosa using immunocytochemical and cytochemical techniques. AB - The absorption of beta-lactoglobulin (BLG) by cultured explants of the normal adult duodenal mucosa has been studied in vitro using immunocytochemical techniques. Membrane filters (1 mm2) were soaked in medium containing BLG and placed on the mucosal surface. Explants were cultured for < or = 60 min, and histological sections were immunostained for BLG. Increasing the BLG concentration in the filters and/or the exposure time increased the number and immunoreactivity of the immunopositive epithelial cells present, suggesting increased BLG absorption. Increased BLG penetration of the duodenal mucosa in untreated coeliac disease was also shown using these techniques. In some studies horseradish peroxidase (HRP) was used as an alternative probe and pin-pointed in epithelial cells by ultracytochemical techniques, confirming vesicular uptake of macromolecules. Colocalisation experiments using BLG and HRP and immunofluorocytochemical techniques suggested linkage between the mechanisms of absorption of both proteins into epithelial cells. Short-term organ culture and protein challenge followed by immunolocalisation has been shown to be of value in studying the absorption of BLG and HRP by the upper small intestine and possibly of other protein macromolecules as well. PMID- 8450383 TI - Distribution of neuromuscular junctions in the bowel affected by hypoganglionosis. AB - Using monoclonal antibody 171B5 against synaptic vesicle proteins, neuromuscular junctions and synapses in the muscle layers of the bowel affected by hypoganglionosis were labeled and their distribution analysed. In the hypoganglionic bowel, there were less synapses in the myenteric plexus and few neuromuscular junctions compared to normal bowels. The bowel dysmotility of the patient with hypoganglionosis appears to be due to inadequate innervation between ganglion cells and smooth muscle cells. PMID- 8450384 TI - Down's syndrome and celiac disease. AB - The association between Down's syndrome (DS) and autoimmune diseases has long been recognized. However, its relationship to celiac disease (CD) has only recently been reported, and a clear-cut association remains to be fully established. We have studied the prevalence of CD in a random sample of 70 individuals with DS. IgA anti-gliadin antibodies (IgA AGAs) were determined in all and found to be positive in nine (13%). In eight, anti-endomysium antibodies (AEAs) were investigated, and jejunal biopsies were performed. AEAs were positive in two, and three had flat intestinal mucosa. The class I and II human leukocyte antigens of two patients with CD were determined. Results were as follows: A2/B8 B39/DR1 DR3/DQW1 DQW2 in one case and A2 A28/B44 B17/DR4 DR5/DQW3 in the other. This implies a 43% prevalence of CD in DS, which is well above that previously found by us in our population (0.62/1,000 live births). We conclude that the association between DS and CD is not fortuitous and suggest that the determination of such serologic markers as IgA AGA and AEA should be part of health assessment in DS patients. PMID- 8450385 TI - Endoscopic and histologic findings in the upper gastrointestinal tract of children with coeliac disease. AB - Frequency of mucosal damage to the esophagus, stomach, and duodenum was investigated in 176 children with coeliac disease (CD) during 230 upper GI endoscopies performed to obtain duodenal biopsy specimens and was compared with findings in 230 age-matched children who underwent endoscopy for upper GI complaints without CD (non-CD patients). To evaluate a possible association with gluten ingestion, we then compared frequency of mucosal damage in patients on a gluten-containing diet and those on a gluten-free Diet (GFD). In children with CD, frequency of esophageal damage seen at endoscopy and of peptic esophagitis shown by histology were significantly lower than in non-CD patients (p < 0.01) due to the very low frequency of mucosal damage in CD children on GFD; however, frequency of columnar metaplasia was significantly higher (p < 0.05). At endoscopy, CD children had a significantly lower frequency of gastric abnormalities, but histology showed a higher prevalence of superficial chronic gastritis (SCG; p < 0.01). SCG was associated with gluten ingestion, since its frequency in CD children on GFD was similar to the frequency in non-CD patients. At endoscopy, frequency of duodenal mucosal damage was similar in CD and non-CD patients. In addition to villous atrophy, histology showed a significantly higher frequency of duodenitis in CD children on a gluten-containing diet (p < 0.001 vs. non-CD patients; p < 0.05 vs. CD children on GFD). Our findings show that the mucosa of the whole upper GI tract can be damaged in CD patients and that the prevalence of some changes is higher with a gluten-containing diet. PMID- 8450386 TI - Duodenal findings on ultrasound in children with Schonlein-Henoch purpura and gastrointestinal symptoms. AB - Abdominal ultrasonic examination was performed in 14 patients with Schonlein Henoch purpura (SHP). Thickening of the duodenal wall was observed in nine (82%) of the 11 with such gastrointestinal (GI) symptoms as severe abdominal pain or bleeding. The thickened duodenal wall showed a high echogenicity. Enlargement of the duodenal lumen was seen in seven (64%) patients with GI symptoms. These findings had been observed in four patients before SHP was diagnosed on the basis of the peculiar skin lesions. In three cases of SHP without GI symptoms, those changes were absent. Four cases of ulcerative colitis, three of bacterial enterocolitis (two Yersinia and one Klebsiella), and five without SHP and any GI problems did not exhibit such duodenal abnormalities. On subsequent endoscopic study, mucosal edema and multiple hemorrhagic erosions were seen, especially at the second portion of the duodenum in two cases of SHP. Biopsy specimens from the duodenum of those cases showed leukocytoclastic vasculitis, suggested by the ultrasound (US) findings. It is important to consider the duodenal changes carefully when US is performed in patients with severe GI symptoms of unknown origin. The characteristic duodenal findings described suggest the differential diagnosis of SHP, which usually requires no surgical intervention. PMID- 8450387 TI - The need for endoscopic biopsy in the diagnosis of upper gastrointestinal graft versus-host disease. PMID- 8450388 TI - Hepatic pseudomass on ultrasound in children with fatty infiltration of the liver. PMID- 8450389 TI - Langerhans' cell histiocytosis presenting with hepatic dysfunction. PMID- 8450390 TI - Unexplained indirect hyperbilirubinemia, hypercholesterolemia, and spur cell formation in two male siblings: a variant of cholesteryl ester deposition. PMID- 8450391 TI - Cholestatic giant cell hepatitis associated with ultrastructural evidence of intrahepatic retroviral infection in a human immunodeficiency virus-seropositive infant. PMID- 8450392 TI - Cecal fecal bezoar. PMID- 8450393 TI - High levels of anti-gliadin antibodies in HIV-infected children. PMID- 8450394 TI - Liver abscess as an unusual complication in sickle cell anemia. PMID- 8450395 TI - The NF-kappa B p65 promoter. AB - The promoter of the human gene encoding the p65 subunit of the transcription factor NF-kappa B was cloned and the nucleotide sequence determined. The p65 promoter lacks both TATA and CCAAT consensus sequences. The p65 promoter contains three consensus binding sites of the transcription factor SP1. In contrast to the promoter of the p50 subunit of NF-kappa B, no sequences predicted to bind NF kappa B are present in the p65 promoter. Phorbol ester (PMA) and phytohemagglutinin (PHA) treatment of Jurkat cells did not activate the p65 promoter in transient transfection experiments. Using different deletion mutants of the p65 promoter, essential promoter elements were mapped. PMID- 8450396 TI - Jurkat-tat but not other tat-expressing cell lines support replication of slow/low type HIV. AB - The Jurkat-tat cell line, carrying the transactivator (tat) gene of HIV-1 IIIB and thus constitutively expressing the tat protein, has the capacity to support replication of HIV isolates obtained from asymptomatic individuals, so called slow/low (s/l) type virus. A major characteristic of the s/l isolates in vitro is their inability to continuously replicate in cells of CD4+ established lines. In contrast, virus isolates designated rapid/high (r/h) obtained from patients in advanced stages of the HIV-infection do not show this restriction in replicative capacity. To analyze whether introduction of the tat protein into certain cell types or an over-expression of the tat protein would render cells permissive for s/l virus replication, the tat gene was transfected into cells of monocytoid and T cell origin. The resulting cell lines were then tested for their susceptibility to infection with s/l and r/h type HIV-1 isolates. The results conclusively show that mere constitutive expression of the tat protein in established CD4+ cell lines will not provide conditions allowing for continuous replication of s/l type virus. Thus, the Jurkat-tat cell line is a unique cell system for long-term propagation of this type of virus. In addition, it is a suitable system to study virus-host cell interactions and control of virus replication. PMID- 8450397 TI - Quantification and comparison of HIV-1 proviral load in peripheral blood mononuclear cells and isolated CD4+ T cells. AB - HIV proviral load was determined by quantitative DNA polymerase chain reaction (PCR) in peripheral blood mononuclear cells (PBMC) and lymphocyte subsets isolated by cell sorter. Provirus measured in PBMC, when expressed as HIV copy number per million CD4+ cells, resulted in values which approximated those obtained from sorted CD4+ T lymphocytes. A cross sectional analysis of HIV proviral load in CD4+ T cells from 25 previously untreated and 30 zidovudine treated seropositive patients with CD4+ T-cell counts between 25 and 802/mm3 demonstrated HIV copy numbers ranging from 1 copy per 10,000 cells in early disease to 1 copy per 10 cells in advanced disease. HIV proviral load can be rapidly assayed by PCR to give a reproducible value which varies over a 1,000 fold range and is positively correlated with cell infectivity as measured by a quantitative micrococulture assay. A less technically demanding assay using PBMC as substrate can give similar results to those obtained with sorted CD4+ T cells. PMID- 8450398 TI - Determination of the etiology of seroreversals in HIV testing by antibody fingerprinting. AB - Fifteen sets of seroreversal serum samples (i.e., an initial specimen confirmed as anti-human immunodeficiency virus, HIV, positive and a 2-4-week follow-up specimen that is anti-HIV negative) were identified from 711,684 military members tested by the U.S. Army HIV screening program from January 1990 to May 1991. We utilized the Miragen Antibody Fingerprinting Assay to determine what proportion of these seroreversals was caused by different or discordant patient samples as opposed to laboratory testing errors. Forty-two percent of these seroreversals demonstrated substantially discordant immunoblot strips representing serum samples from different patients. We recommend utilization of this antibody fingerprinting assay to help determine the etiology of HIV seroreversal specimens. PMID- 8450399 TI - Anthropometric, metabolic, and immunological effects of recombinant human growth hormone in AIDS and AIDS-related complex. AB - Metabolic and anthropometric changes induced by "pharmacological" versus "physiological" doses (5.0 vs. 2.5 mg, every other day) of recombinant human growth hormone (rhGH) were compared in 10 human immunodeficiency virus-positive patients with AIDS or AIDS-related complex. Five patients were randomly assigned to each treatment schedule in a 3-month prospective, double-blind clinical trial. Three of the 10 patients, none taking zidovudine and all with low initial CD4 counts, were withdrawn during the study due to acute opportunistic infections. During treatment, insulin-like growth factor-1 (IGF-1) levels increased significantly (p < 0.05) in the pharmacological hGH treatment group, whereas no significant change was observed in IGF-1 in the physiological dose rhGH group. In the pharmacological hGH treatment group, weight loss preceding the study was reversed (p < 0.05) in each of the four patients who completed the study. This weight gain was associated with increases (p < 0.05) in lean body mass and total body water, with concomitant decreases in fat mass (p < 0.05) and urinary nitrogen excretion. Muscle power and endurance, as assessed by standardized omnikinetic dynamometry, also improved. All four patients lost weight again (p < 0.05) 6 weeks after completion of the study and termination of rhGH treatment. Minor positive changes in body composition were also observed in the physiologic dose hGH group. The pharmacological dose of hGH was associated with minor increments (p < 0.05) in fasting plasma glucose, insulin, and C-peptide concentrations, which were of negligible clinical significance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450400 TI - HIV-related ocular microangiopathic syndrome and cognitive functioning. AB - Ocular microangiopathic syndrome is found frequently in patients with AIDS or severe HIV infection. Symptoms of this microvascular syndrome can include cotton wool spots, hemorrhages, and Roth's spots. The clinical and functional significance of HIV-related ocular microangiopathic syndrome has not been clarified as yet. The objective of this study was to evaluate a possible association between HIV-related ocular microangiopathic syndrome and cognitive functioning. Thirty-seven patients infected with HIV (24 with AIDS) underwent ophthalmological and neuropsychological examination. HIV-related ocular microangiopathic syndrome was measured by counting the number of cotton-wool spots in both eyes. Neuropsychological examination included five standardized tests, with the first three primarily measuring function of short-term memory; these tests were as follows: the Auditory-Verbal Learning Test, the Benton Test, the Stroop Colour Word Test, the Trail-Making Part B test, and the Vocabulary for Measuring Premorbid Intelligence test. HIV-related ocular microangiopathic syndrome was found in 15 patients with AIDS (62.5%), and in one patient, staged Walter Reed 5. In 10 patients, one eye was affected (mean count of cotton-wool spots 1.5). In six patients, both eyes were affected (mean count of cotton-wool spots 7.0). Univariate correlations between the number of cotton-wool spots in both eyes and test scores were as follows: Auditory-Verbal Learning Test: 0.56 (p < 0.001); Benton Test: 0.51 (p < 0.001); Stroop Colour and Word: 0.50 (p < 0.001); Trail-Making Part B: 0.15 (not significant); Vocabulary for Measuring Premorbid Intelligence: -0.05 (not significant). Multiple correlation between the test scores and the number of cotton-wool spots was 0.70 (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450401 TI - Weekly doxorubicin in the treatment of patients with AIDS-related Kaposi's sarcoma. AIDS Clinical Trials Group. AB - Fifty-three patients with AIDS-related Kaposi's sarcoma and no previous treatment with cytotoxic chemotherapy enrolled in a phase II multicenter study to evaluate the safety and efficacy of weekly doxorubicin treatment. Doxorubicin was given intravenously at a dose of 15 mg/m2. Patients were stratified for purposes of analyses by tumor burden and coexistence of HIV-associated signs and symptoms; stratum I included patients with cutaneous disease alone and no symptoms, and stratum II included patients with visceral disease, tumor-associated edema, a previous opportunistic infection, or systemic symptoms. Fifty-one patients were evaluable for toxicity and 50 for tumor response. Five patients had a partial response (10%); 32, a minor response (64%); 12, no change (24%); and one, progression (2%) as the best measurable response. Partial response durations ranged from 4 to 14 weeks. Fifteen patients subsequently showed progression while on treatment. A significantly greater number of patients in stratum I (20.1%) had a partial response compared with those in stratum II (0%, p = 0.009). The major toxicities included nausea (37%), stomatitis (9.8%), mucositis (13.7%), and moderate to severe neutropenia (71%). Neutropenia was dose limiting and resulted in discontinuation of doxorubicin in 18% of the patients. Two patients developed cardiac toxicity. In conclusion, doxorubicin treatment induced relatively few tumor responses and remission durations were short. Treatment was limited by a high rate of toxicity. PMID- 8450402 TI - Beta-carotene in HIV infection. AB - beta-Carotene has been reported to have an immunostimulatory effect. Recent studies suggest that beta-carotene supplementation can increase CD4 counts in HIV infected patients. Our double-blind, placebo-controlled clinical trial was designed to test the efficacy of beta-carotene in raising CD4 counts in HIV infected patients. Twenty-one HIV-seropositive patients were randomized to receive either beta-carotene, 180 mg/day or placebo for 4 weeks, and then crossed over to receive the alternative treatment for the following 4 weeks. beta Carotene resulted in a statistically significant increase in total WBC count (p = 0.01), % change in CD4 count (p = 0.02), and % change in CD4/CD8 ratios (p = 0.02) compared to placebo. The absolute CD4 count, absolute CD4/CD8 ratio, and total and B-lymphocytes all increased on carotene and fell during placebo, but these differences did not reach statistical significance. No toxicity was observed on either treatment. beta-Carotene appears to have an immunostimulatory effect in HIV-infected patients. Further studies are needed to demonstrate whether beta-carotene has a role as adjunct therapy in treatment of HIV-infected patients. PMID- 8450404 TI - Reporting of HIV-1 infection through the provision of essential services. PMID- 8450403 TI - HIV infection in autologous and allogeneic bone marrow transplant patients: a retrospective analysis of the Marseille bone marrow transplant population. AB - Twelve HIV-positive patients who either underwent or seroconverted after bone marrow transplantation (BMT) at the University of Marseille between 1981 and 1985 were reviewed in order to observe their rates of development of AIDS. Two patients were HIV positive prior to transplantation, while ten seroconverted after transplantation. Six patients underwent autologous BMT and six underwent allogeneic BMT; all of their respective donors were seronegative. Eleven patients developed AIDS (92%), with a mean AIDS-free time (AFT) of 1 year 8 months after BMT. Seven of those subjects died, with a mean survival over a 5-year follow-up period of 2.14 years after BMT. Five autologous recipients had a mean AFT of 2 years 3 months, with the sixth patient being AIDS free. The mean AFT for the allogeneic recipients was 1 year 2 months (p = NS), all of whom developed AIDS. These data suggest that the development of AIDS was rapid from the time when our patients seroconverted. However, this was not initially accompanied by poor survival. In summary, BMT may be indicated for HIV-positive patients who required myeloablation, despite an enhanced development of AIDS. PMID- 8450405 TI - Maternal and neonatal characteristics associated with HIV infection in infants of seropositive women. AB - In this prospective study of infants born to human immunodeficiency virus (HIV) seropositive mothers, neonatal and maternal characteristics of infected and noninfected infants were compared to determine the factors that may be associated with or contribute to vertical transmission of HIV. Of 134 infants entered as newborns in the study, 31 have definite serological and/or clinical evidence of infection and 103 are considered noninfected (transmission rate, 23.1%). Significantly more of the infected infants had birth weights below 2,500 g (48.4% versus 22.3%), and more infected infants were found to be small for gestational age (16.2% versus 5.8%). A greater number of infected infants experienced two or more problems in the neonatal period than noninfected infants (51.6% versus 24.2%). The incidence of confirmed and suspected bacterial infections was also significantly increased in the infected group. Multiple logistic regression analysis indicated low birth weight had the strongest association with vertical transmission of HIV. There was no significant difference between the two groups in mean maternal age at first pregnancy, mother's marital status, education, type of family, or past history of type of substances abused. Mothers who transmitted HIV to their infants had a trend towards a higher frequency of clinical chorioamnionitis (16.1% versus 5.8%), reported sexually transmitted diseases during pregnancy (45.2% versus 22.3%), and continued illicit drug use (67.7% versus 49.0%). In this group of infants, low birth weight, poor intrauterine growth, neonatal infections and possibly maternal chorioamnionitis, STDs during pregnancy, and continued drug use are associated with vertical transmission of HIV. PMID- 8450406 TI - Factors associated with human immunodeficiency virus seroconversion in homosexual men in three San Francisco cohort studies, 1984-1989. AB - A total of 83 HIV seroconversions occurred between 1984 and 1989 in three San Francisco cohorts of homosexual and bisexual men. A nested case-control analysis was performed to assess the risk of seroconversion associated with sexual practices. Strong associations were found with total number of intercourse partners and receptive anal intercourse. Weaker, but significant associations were found with receptive oral intercourse. Individuals reporting condom use with some partners were more likely to become infected than those reporting no condom use. Some of this difference was due to increased numbers of sexual partners among those reporting some condom use, but the association remained significant in multivariate analyses. This observation indicates there is some unmeasured risk associated with those using condoms, such as more HIV seropositive partners. PMID- 8450407 TI - HIV-1 and HTLV-I in sexually transmitted disease clinics in the Dominican Republic. AB - A cross-sectional seroprevalence study of human immunodeficiency virus type 1 (HIV-1) and human T-cell lymphotropic virus type I (HTLV-I) was undertaken among 494 attendees in two Santo Domingo sexually transmitted disease clinics in 1989. All participants were evaluated for Neisseria gonorrhoeae, Chlamydia trachomatis, syphilis, and genital ulcers. Of the 494 participants, 15 (3.0%) were positive for HIV-1 and 14 (2.8%) were positive for HTLV-I. Twelve of 371 (3.2%) men were HIV-1 seropositive: 0 of 68 homosexual/bisexual and 12 (4.0%) of 302 heterosexual men (one seronegative male could not be classified). Three (2.4%) of 123 women were HIV-1 seropositive. One (1.5%) homosexual/bisexual man, five (1.7%) heterosexual men, and eight (6.5%) women were HTLV-I seropositive. Among heterosexual men, HIV-1 was associated with multiple lifetime sex partners (O.R. = 5.9; 95% C.I. = 1.4, 23; p = 0.007). HIV-1 was associated with genital ulcer disease among women (p = 0.004). Among women, HTLV-I was associated with professional sex work (O.R. = 18; 95% C.I. = 2.1, > 100; p = 0.001). These findings suggest the need for control of sexually transmitted diseases and targeted educational programs for prevention of HIV-1 and HTLV-I among individuals with high-risk behaviors in the Dominican Republic. PMID- 8450408 TI - Serologic validation of HIV infection in a tropical area. AB - We have defined human immunodeficiency virus type 1 (HIV-1) serologic reactivity in Brazilians living in an area endemic for tropical diseases. Enzyme-linked immunosorbent assay (ELISA) and Western blot (WB) analyses were performed on 342 patients with diseases including Chagas' disease, schistosomiasis, typhoid fever, helminthiasis, and cutaneous and visceral leishmaniasis. Nine percent of the visceral leishmaniasis patients' sera reacted in the HIV-1 ELISA but all were WB negative. All other sera from these patients were HIV negative. A total of 224 HIV-1 ELISA repeatedly positive sera also were HIV-1 WB tested. They were drawn from a total population of 19,230 individuals, including AIDS patients, blood donors, homosexual men, intravenous drug users, pregnant women, individuals with hemophiliac, and tuberculosis and sexually transmitted disease patients. The WB results were analyzed using five different interpretive criteria for WB positivity. The Centers for Disease Control (CDC) and the World Health Organization (WHO) criteria were the most sensitive and specific for identifying HIV-1-infected individuals. The WB pattern was similar to that seen in the United States. Envelope (ENV) protein antibodies were highly predictive of HIV-1 infection; none of the AIDS patients lacked ENV protein reactivity. We conclude that among the tropical diseases studied, only visceral leishmaniasis is associated with false-positive HIV-1 ELISA tests. Current CDC and WHO criteria for interpretation of HIV-1 WB tests are appropriate for Brazil. PMID- 8450409 TI - HIV infection among long-distance truck drivers in Delhi, India. PMID- 8450410 TI - HIV-2 infection in HIV-1 indeterminate sera in Spain. PMID- 8450411 TI - Evidence of HTLV-II infection in Guinea, West Africa. PMID- 8450412 TI - HTLV-I/II and multiple sclerosis in Buenos Aires. PMID- 8450413 TI - HTLV-I in Alaska Natives. PMID- 8450414 TI - Toxicity of the mitochondrial poison dequalinium chloride in a murine model system. AB - Dequalinium chloride (DECA), a cationic, lipophilic mitochondrial poison, selectively targets the mitochondrial membrane of certain epithelial carcinoma cells, in which it inhibits cellular energy production. It has demonstrated potency as a cytotoxic agent specific for carcinomas and may provide a novel approach for cancer therapy, either as a single agent or as an adjunct to conventional chemotherapy. The purpose of this study was to determine the toxicity of DECA in the murine model. One hundred female BALB/c mice were divided into three schedule groups. Group one received a single intraperitoneal (ip) dose of DECA at 10, 15, 20, or 25 mg/kg of body weight. Group two received DECA at 6, 7, 8, 9, or 10 mg/kg ip every other day (QOD), and group three received DECA at 10, 11, 12, 13, or 14 mg/kg ip every 7 days. Over a 30- to 60-day period, acute and subchronic toxicities were evaluated on the basis of the following clinical parameters: respiratory distress, weight loss, and mortality. After a single ip administration, we found a maximum tolerated dose of 15 mg/kg and a lethal dose (LD50) of 18.3 mg/kg. Single ip doses of 20 and 25 mg/kg produced > 50% mortality. Histologic examination of the tissues revealed significant damage to the liver and kidneys, with pulmonary congestion occurring secondary to renal hepatic failure. A cumulative assessment revealed that 60% of the animals tolerated 15 doses of 6 and 7 mg/kg QOD and that 100% tolerated 5 doses of 11 and 12 mg/kg (every 7 days). Higher DECA doses under either regimen induced severe toxic effects and mortality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450415 TI - Simultaneous assessment of the intravenous and oral disposition of the enantiomers of racemic nimodipine by chiral stationary-phase high-performance liquid chromatography and gas chromatography/mass spectroscopy combined with a stable isotope technique. AB - An enantioselective method of high specificity and sensitivity for the determination of the enantiomers of two racemic 1,4-dihydropyridine compounds after simultaneous oral (po) and intravenous (iv) administration is reported. The method is suitable for the simultaneous administration by two different routes of a racemic drug labeled with stable isotopes and unlabeled racemate. For workup, an internal racemic standard labeled with a different number of stable isotopes is added. After separation of the enantiomers by chiral stationary-phase high performance liquid chromatography and subsequent analysis by gas chromatography/mass spectroscopy (GC/MS) with selected ion detection, the R and S enantiomer concentrations arising from i.v. and p.o. administration can be precisely measured because of their mass difference. This method has been applied to assess the disposition of the R and S enantiomers of nimodipine and nitrendipine after simultaneous i.v. and p.o. administration. The assay is highly specific and sensitive, with a limit of quantification per enantiomer of 0.1 ng/mL after extraction of 0.5 mL of human serum samples and monitoring the M- ions in the electron capture, negative ion chemical ionization mode. The calibration curve was linear in the range 0.1-100 ng/mL. Within- and between-day precision were satisfactory (coefficient of variation, < 10%). Enantiomeric excess in the range 0-100% could be accurately determined. Comparison of the enantioselective method with the achiral method (GC/MS only) gave good agreement. PMID- 8450416 TI - Voltammetric behavior of berenil. AB - Berenil is reduced on mercury drops electrode in buffered aqueous media. The reduction of -N=N- group is controlled by diffusion. Polarographic waves are of analytical usefulness. The hydrogen discharge is favored by the basic centers of the molecule in Co(II)/ammonia-buffered media. PMID- 8450417 TI - Effects of age on the pharmacokinetics of piroxicam in rats. AB - This study examined the effects of age on the pharmacokinetics of piroxicam in rats. Two groups of rats, aged 5 and 24 months, were administered 1 mg of piroxicam per kg intravenously, and blood samples were withdrawn for up to 120 h. Protein binding studies, with pooled serum from each age group were also performed. Piroxicam concentrations were determined by HPLC analysis, and pharmacokinetic parameters were characterized by area-moment analysis. Plasma piroxicam concentrations declined in both age groups in a biexponential fashion, with half-lives of 5.9 +/- 0.7 h (mean +/- SD) in the young rats and 30.6 +/- 9.9 h in the old rats. Total clearance in the young rats was 0.048 +/- 0.012 L/h/kg, whereas that in the old rats was 0.021 +/- 0.003 L/h/kg. The steady-state volume of distribution in the young rats was 0.42 +/- 0.05 L/kg, and that in the old rats was 0.56 +/- 0.10 L/kg. There was a statistically significant difference between these parameters calculated for each age group. Piroxicam is a highly plasma protein-bound drug; the fraction unbound in the young rats was determined to be 0.067 +/- 0.022, and that in the old rats was determined to be 0.134 +/- 0.065, or twice that in the young rats. Differences in protein binding were due, in part, to a 20% decreased albumin concentration in the old rats; however, there was also a decrease in the number of binding sites and/or the binding affinity with aging.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450418 TI - Quaternary salts of 3,3'-bis-pyridinium monooximes: synthesis and biological activity. AB - Two new series of asymetrically substituted 3,3'-bis-pyridinium monooximes bridged by oxopropane and propane groups were synthesized and characterized by spectral data and acid dissociation constants (pKas). Both the in vitro reactivation potency, in experiments with lyophilized electric eel acetylcholinesterase (AChE) inhibited by diisopropylfluorophosphate, and in vivo protection efficacy against diisopropylfluorophosphate intoxication in mice of these compounds were evaluated and compared with those of trimedoxime and 2 pyridine-aldoxime methiodide. The compounds were also evaluated for in vitro inhibition of AChE. The compounds with the oxopropane link were stronger inhibitors and weaker reactivators than the corresponding propane derivatives. No significant correlation was observed among pKa, oxime inhibition of AChE, reactivation of inhibited AChE, and protection index. Changing substituents in pyridine rings or altering linking groups between pyridine rings did not improve antidotal efficacy compared with trimedoxime and 2-pyridine-aldoxime methiodide. PMID- 8450419 TI - Synthesis and antitumor activity of pyrido-amsacrine analogues and related compounds. AB - The pyrido derivatives of amsacrine [4'-(9-acridinylamino) methanesulfon-m anisidine] were prepared and evaluated in the L1210 leukemia system. Almost all the pyrido analogues were tighter DNA-binding ligands than the corresponding amsacrine compounds. The significant inhibition of L1210 produced by pyrido acridan-7-ones demonstrates that the anilino side chain is not essential for activity, although most of the compounds did not have improved activity compared with amsacrine. PMID- 8450420 TI - A system approach to pharmacodynamics. Input-effect control system analysis of central nervous system effect of alfentanil. AB - Virtually all biological variables, including those affected by drugs, are subject to adaptive self regulation. In the description of the pharmacodynamics (PD) of drugs, it may be necessary to consider the endogenous control system (ECS) as an integral part of the PD. A PDECS model based on system analysis principles is presented and tested on PD data for alfentanil considering the central nervous system activity quantified by a power spectrum analysis of the electroencephalogram. The model was tested in terms of a proposed relative prediction performance criterion that measures the accuracy of future predictions relative to how well the model describes (fits) the past effect data. A mean value of 80% (standard deviation, 28) for relative prediction performance indicates that the model performs well when challenged by the complex multiple infusion scheme used in the test. The overshoot phenomenon observed in the data is considered by the PDECS model as a ECS-based tolerance phenomenon. The proposed development of tolerance is modeled as a variable gain in the ECS processing that influences the effect. Although the development and loss of tolerance is determined by a single rate constant in the tolerance model, the rates of increase and decrease of tolerance may be substantially different. Contrary to other PD tolerance models, the proposed PDECS approach models the tolerance in terms of an effect deviation from an ECS set point. The intrinsic (no tolerance) effect of the drug is isolated in terms of an open loop (no feedback) effect. PMID- 8450421 TI - Synthesis of galactose derivatives that render lectin-induced agglutinating ability to liposomes. AB - Three galactose (Gal) derivatives, Gal beta 1-n-C16H33 (1), Gal beta (1-4)-Glc beta 1-n-C16H33 (2), and Gal beta 1-(CH2CH2O)3-n-C16H33 (3), were synthesized and incorporated into liposomes prepared from egg yolk lecithin. Agglutination of these liposomes with Ricinus communis agglutinin was examined by following the change of turbidity. Liposomes containing 3 were effectively agglutinated in contrast to the cases of 1 and 2, suggesting that the oxyethylene groups act as a favorable spacer to extrude Gal groups into the water. Differential scanning calorimetry showed that 3 was mixed with egg yolk lecithin at room temperature, but 1 and 2 were in the gel state, resulting in the phase separation that makes the recognition of Gal residue with Ricinus communis agglutinin difficult. PMID- 8450422 TI - Solution- and solid-state structures of N-desmethylnefopam hydrochloride, a metabolite of the analgesic drug. AB - The solid-state structure of (+/-)-N-desmethylnefopam hydrochloride (1), a metabolite of the analgesic drug, was determined by single-crystal X-ray diffraction analysis. Compound 1 gave crystalline prisms belonging to the orthorhombic Pcab space group, and at ambient temperature (293 K), a = 9.939(2), b = 14.479(1), c = 20.148(3) A, V = 2899.5(8) A3, Z = 8, R(F) = 0.045, and Rw(F) = 0.025. The benzoxazocine ring of crystalline 1 is twisted into the boat flattened (chair) [BfC] conformation, the phenyl ring resides in a relatively sterically unhindered exo-type ring position, whereas the O atom and NCH2Ar occupy sterically hindered positions between "boat" and "chair" regions. Dissolution of BfC crystalline 1 in CD2Cl2 solvent affords a dynamic conformational equilibrium (involving the putative twist-chair-flattened (chair) conformer) as shown by line broadening and weighted time-averaged vicinal coupling constants [-OCH2CH2N- segment] in the 1H NMR spectrum. The solution state weighted time-averaged 50(1) degrees O-CH2-CH2-N dihedral angle, calculated by the R-ratio method, shows that the BfC conformation is the major contributor to time-averaged structure. PMID- 8450423 TI - Pharmacokinetic profile of flosequinan in patients with compromised renal function. AB - The pharmacokinetics of flosequinan and its major active metabolite (BTS 53,554, 7-fluoro-1-methyl-3 methylsulfinyl-4-quinolone, 1) were investigated following a single oral dose of 100 mg of flosequinan in 20 patients with severe renal dysfunction (creatinine clearance, < or = 25 mL/min). Plasma and urine samples were collected for 144 h post-dose and analyzed by high-performance liquid chromatography. Flosequinan was well absorbed and rapidly eliminated, reaching mean peak concentrations in plasma of 1.37 +/- 0.67 micrograms/mL at 1.6 +/- 1.4 h post-dose. As in healthy volunteers, approximately 1% of the administered dose of flosequinan was excreted unchanged in urine. Renal clearance of flosequinan was decreased by an average of 20% relative to healthy volunteers. The active metabolite 1 reached mean peak concentrations in plasma of 2.22 +/- 0.58 micrograms/mL at 10.9 +/- 5.9 h post-dose and yielded mean areas under the curve of concentration in plasma versus time twice that of healthy volunteers. Elimination rates for 1 decreased by half, and the mean elimination half-life increased to 68.5 +/- 24.2 h compared with 34.5 +/- 6.7 h for healthy volunteers. The decrease in elimination rate resulted in higher exposure to total active drug substance (flosequinan plus metabolite) for renal patients than for healthy volunteers. These results suggest dosage adjustments may be necessary in patients with severe renal dysfunction to prevent excessive accumulation of 1 with repeated dosage of flosequinan. PMID- 8450424 TI - Pyridazine derivatives. XI: Antihypertensive activity of 3 hydrazinocycloheptyl[1,2-c]pyridazine and its hydrazone derivatives. AB - 3-Hydrazinocycloheptyl[1,2-c]pyridazine (4) and its hydrazone derivatives 3-[N1 (isopropylidene)]hydrazinocycloheptyl[1,2-c]pyridazine [correction of hydrazinocyclohexyl] (5) and 3-[N1-(isobutylidene)]hydrazinocycloheptyl[1,2 c]pyridazine (6) were prepared, and their activity against genetic, neurogenically-induced, and deoxycorticosterone acetate -NaCl-induced hypertension was found to be at least as great as that of hydralazine. The results of studying vasorelaxation of rat aorta by 4 and hydralazine suggest that both these compounds owe their antihypertensive activity to direct relaxation of vascular smooth muscle. PMID- 8450425 TI - Ketoprofen-probenecid interaction in the rat: a probenecid concentration dependent stereoselective process. AB - Probenecid (PB) is believed to interact with the chiral nonsteroidal anti inflammatory drug ketoprofen (KT) through competition for glucuronide conjugation and subsequent renal and/or biliary excretion of formed KT conjugates. It is unknown whether the interaction is dependent on PB concentration and whether both KT enantiomers are affected to the same extent. We measured intact and conjugated R-KT, S-KT, and PB in the plasma and urine of female Sprague-Dawley rats after intravenous doses of 10 mg of racemic KT per kg and 0, 25, 50, 100, 150, 175, and 200 mg of PB per kg. Elevated levels of both enantiomers were observed, with S-KT being affected to a much greater extent. Significant positive correlations were found between the concentrations in plasma of KT enantiomers and PB at various sampling times, with the strongest correlations being found at 2 h for R-KT (r = 0.708) and 1.5 h for S-KT (r = 0.913). The areas under the concentration-time curve (AUC) from 0-24 h for R-KT (r = 0.697) and S-KT (r = 0.848) also showed strong correlation with AUC of PB. Our data show that as the dose of PB was increased (0-200 mg/kg), the mean S-KT/R-KT ratios for both the AUC and the fraction of the dose excreted as enantiomer conjugates in urine over 24 h increased progressively from 12.1 +/- 2.3 to 27.6 +/- 5.0 and from 6.8 +/- 0.7 to 36.4 +/- 12.2, respectively. These findings clearly demonstrate that the KT-PB interaction in the rat is a PB concentration-dependent process.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450426 TI - Kinetic analysis of glycyrrhetic acid, an active metabolite of glycyrrhizin, in rats: role of enterohepatic circulation. AB - The role of enterohepatic circulation of glycyrrhetic acid (GA) in rats was determined by kinetic analysis of GA. The concentrations of GA in the plasma of the control rat (without bile duct cannulation) during the first 5 h after intravenous (iv) administration of GA (2, 5, 10, and 20 mg/kg) were similar to those in the bile duct-cannulated rat at each dose. No significant difference was observed in the values of the terminal half-life, the total body clearance, the distribution volume at steady state, the area under the curve of concentration in plasma versus time, and the mean residence time in each dose between both groups. When GA (2, 5, 10, and 20 mg/kg) was administered i.v. to the bile duct cannulated rat, excretion of unchanged GA in bile was < 1% of each dose, that of the acid-hydrolyzed products was 14-16%, and that of GA-3-O-glucuronide was only 1-2%. In the control rat, a secondary peak of GA concentration was observed 12 h after i.v. administration of GA (20 mg/kg). The enterohepatic circulation of GA was confirmed by the linked-rat method in which bile of the donor rat after i.v. administration of GA (20 mg/kg) was allowed to flow directly into the duodenum of the recipient rat. GA was found in the plasma of the recipient rat after 6 h, and its concentration reached the maximum (approximately 0.5 microgram/mL) 8-12 h after dosing the donor rat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450427 TI - Influence of pH on release of phenytoin sodium from slow-release dosage forms. AB - Physicochemical factors influencing the release of phenytoin sodium from slow release dosage forms were studied. Some of these factors were solubility and intrinsic dissolution rate as functions of pH, type of dosage form, pH of dissolution medium used, and conversion of the sodium salt to free acid (phenytoin). The innovator's product, Extended Phenytoin Sodium Capsule (Dilantin Kapseal, 100 mg, Parke-Davis), and two experimental formulations (one nondisintegrating tablet containing polymeric materials and the other a solid dispersion in an erodible matrix) served as the slow-release dosage forms. The sodium salt converts to practically insoluble phenytoin in the gastrointestinal pH range of 1 to 8. Due to such a conversion inside or at the surface of slow release dosage forms, the release of drug in this pH range was incomplete. The extent of drug release also varied with the type of formulation used. In contrast, complete dissolution could be obtained in water because the pH of the medium gradually rose from approximately 6 to approximately 9.2 where the drug solubility was higher. Although several phenytoin sodium products might have similar dissolution rates in water, the extents of drug release under gastrointestinal pH conditions (pH 1-8) could differ greatly, thus supporting the Food and Drug Administration recognition that the similarity in dissolution profiles in water does not assure that the products are bioequivalent. The reported lower steady-state level of phenytoin in human plasma following oral administration of a slow-release dosage form may be related to incomplete drug release. PMID- 8450428 TI - Description and simulation of a multiple mixing tank model to predict the effect of bile sequestrants on bile salt excretion. AB - A nonlinear, multicompartment mixing tank model based on human physiologic parameters from the literature and in vitro bile salt sequestrant binding parameters was integrated numerically to simulate bile salt excretion. The model focuses on the transit of bile salts and resin, bile salt binding, and bile salt reabsorption as a means of gaining insight into the functioning of bile sequestrants in the gastrointestinal tract and the effect of reabsorption of bile salts on the sequestering process. The series of compartments through the ileal region were tested over a range of parameter values, and the results were compared with bile salt output from ileostomy patient data to validate the model without resin. In simulations incorporating resin with a reversible binding scheme, fecal bile salt output was 2.37 (+/- 0.6) x 10(-3) mol/day compared with 2.64 (+/- 1.1) x 10(-3) mol/day for human data. Assuming irreversible bile salt binding resulted in predictions of fecal bile salt excretion greater than three times physiologic values. The results of these simulations support the hypothesis that the lack of efficacy of bile sequestrants is due to the displacement of bound bile salts from the sequestrant as a consequence of anion competition and bile salt reabsorption. Gastric emptying effects and the timing of resin doses have also been investigated with the model. PMID- 8450429 TI - Determination of the enantiomers of a new 1,4-dihydropyridine calcium antagonist in dog plasma by achiral/chiral coupled high-performance liquid chromatography with electrochemical detection. AB - An achiral/chiral coupled high-performance liquid chromatographic method with electrochemical detection was developed for the determination of the enantiomers of a new dihydropyridine calcium blocker, methyl (+-)-4,7-dihydro-3-isobutyl-6 methyl-4-(3-nitrophenyl)- thieno[2,3-b]pyridine-5-carboxylate (1), in dog plasma. The assay showed linearity over the range 1-200 ng/mL for the two enantiomers. The limit of determination was 1 ng/mL for each analyte. The assay precision was < 9%, with relative errors of -5.7 to +6.9% at 3 and 30 ng/mL levels of both the enantiomers. The method was applied to a pharmacokinetic study of the enantiomers of 1 in beagle dogs after oral administration of racemic 1. PMID- 8450430 TI - Degradation and release properties of pellets fabricated from three commercial poly(D,L-lactide-co-glycolide) biodegradable polymers. AB - Poly(D,L-lactide-co-glycolide, 50:50) samples of similar molecular weight were obtained from three commercial sources and were characterized by gel permeation chromatography, differential scanning calorimetry, X-ray powder diffraction, viscometry, and proton nuclear magnetic resonance spectroscopy. Pellets were prepared by melt-pressing spray-dried polymer with a 4-mm standard concave punch and die set and a thermostated holder of original design. Amaranth (5% w/w) was incorporated in pellets used for release studies. Degradation and release studies were conducted at 37 degrees C in pH 7.2 phosphate buffered saline. The molecular weights of all polymers were found to decrease continuously after exposure to phosphate buffered saline. All polymers showed two distinct regions of molecular weight decrease. Mass loss experiments for all polymers resulted in sigmoidal curves typical of polymers undergoing bulk hydrolysis. The onset of mass loss (defined as 10% mass loss) was found to differ by as much as 6 days among the three polymers studied. The release studies showed an initial burst of release followed by a period of 15-25 days during which little or no dye was released. A second phase of release followed, lasting approximately 10 days, until all dye was released. The time at which release began slightly preceded the onset of mass loss. PMID- 8450431 TI - Biomembrane permeation and stereochemistry. PMID- 8450432 TI - Measurements of corneal curvature. PMID- 8450433 TI - Corneal topography of excimer laser photorefractive keratectomy. AB - The application of the 193 nm excimer laser for keratorefractive surgery promises to deliver a higher degree of precision and predictability than traditional procedures such as radial keratotomy. The development and evaluation of keratorefractive surgery have benefited from the parallel advances made in the field of corneal topography analysis. We used the Computed Anatomy Topography Modeling System (TMS-1) to analyze a Louisiana State University (LSU) Eye Center series of patients who had photorefractive keratectomy for the treatment of myopia with the VISX Twenty/Twenty excimer laser system. The excimer ablations were characterized by a relatively uniform distribution of surface powers within the treated zone. In the few cases that exhibited marked refractive regression, corneal topography analysis showed correlative changes. With topographical analysis, centration of the ablations relative to the center of the pupil could be evaluated. Marked improvement in centration occurred in the patients of LSU Series IIB in which the procedure to locate the point on the cornea directly over the pupil's center during surgery was refined. Corneal topographical analysis provides objective measures of keratorefractive surgical results and is able to measure the precise tissue removal effect of excimer laser ablation without the uncertainties caused by measuring visual acuity alone. Our observations forecast the need for improved aids to center the laser ablations and for the development of a course of treatment to prevent post-ablation stromal remodeling. PMID- 8450434 TI - When keratometric measurements do not accurately reflect corneal topography. AB - The keratometer has been the standard for measuring corneal curvature for decades and until recently seemed sufficient for most clinical situations. However, it measures only four points from a small region of the cornea and assumes that the cornea is symmetrical. We document with a number of examples a variety of clinical cases in which keratometry provides either incomplete or frankly misleading information. We believe that corneal topography is now an invaluable clinical tool and will replace the keratometer in standard clinical practice. PMID- 8450435 TI - Topographical analysis of the centration of excimer laser photorefractive keratectomy. AB - A major advantage of myopic photorefractive keratectomy (PRK) is the precision with which the excimer laser ablates corneal tissue. But like other refractive surgery procedures, PRK must solve the problem of accurately centering the treatment zone. We present our technique for PRK centration with postoperative corneal topographic data on 110 patients from Phase IIB and III of the clinical trials. The distance between the center of the post-PRK flat zone and the corneal vertex was determined by topography in millimeters and meridian degrees. On average, treatment zones were decentered down and right 0.52 mm at 196.74 degrees; 92.73% were centered within 1.00 mm, while 57.27% were within 0.50 mm. The centration data were correlated to postoperative visual acuity as well as treatment zone diameter. Mean uncorrected visual acuity was 20/20 for decentrations up to 1.00 mm but fell to 20/30 for deviations greater than 1.00 mm. Best corrected acuity was also preserved below 1.00 mm but compromised above this level. No difference in decentration was found between 4.5 mm and 5.0 mm ablation zones. Our findings indicate that PRK centration is accurate within 1.0 mm in over 92% of cases and that visual acuity is relatively preserved despite deviations from perfect centration. Further technical improvements will enhance the accuracy of PRK. PMID- 8450436 TI - Centration of excimer laser photorefractive keratectomy relative to the pupil. AB - The centration of excimer laser photorefractive keratectomy (PRK) is critical to the procedure's success. We evaluated PRK centration in 49 patients using the EyeSys topography system. Ablation zone centration was measured from the corneal vertex and from the pupillary center using the pupil-finding software. Centration was measured more accurately from the pupillary center (0.40 mm) than from the corneal vertex (0.44 mm). Right eyes were decentered less than left eyes. There was an unpredictable correlation between amount of decentration and postoperative visual acuities. The ability to measure centration of keratorefractive procedures precisely from the pupil is an important advance in topography technology. PMID- 8450437 TI - Corneal topography following excimer photorefractive keratectomy for myopia. AB - Corneal topographic analysis was performed on 97 consecutive eyes with at least one month follow-up after excimer laser photorefractive keratectomy for myopia. Centration of the ablated zone was documented in all eyes at the one month postoperative examination with the Topographic Modeling System (Computed Anatomy Inc., NY). Thirty-seven percent of eyes were within 0.25 mm of the pupillary center (PC); 48% of eyes were between 0.25 and 0.50 mm, 13% were between 0.50 and 1.00 mm, and 2% were more than 1.00 mm from the PC. The greatest amount of decentration was 1.50 mm. The mean decentration was 0.36 mm. The surface regularity index (SRI), which is a measure of the optical performance of the cornea, was significantly less at the sixth postoperative month than at the first postoperative month (P = .013). No correlation between the SRI and the amount of decentration was found. Four main patterns of ablation were noted by differential topographic analysis at the one month interval. A central uniform ablation was present in 45% of eyes; "semicircular ablations" were present in 33% of eyes, a "keyhole" ablation pattern in 12%, and a curious "central bump" ablation pattern in 10%. Corneal topographic analysis was a useful tool for documenting and quantitating results following excimer photorefractive surgery. PMID- 8450438 TI - Effective spherical aberration of the cornea as a quantitative descriptor in corneal topography. AB - Following excimer laser photorefractive keratectomy and other refractive surgical procedures, complaints of halos, glare, and monocular diplopia are common. These procedures increase the asphericity of the cornea, which may cause the optical distortions. We used ray tracing techniques to estimate the longitudinal monochromatic aberration of the cornea from the measured corneal topography (effective spherical aberration) in 15 normal eyes with varying degrees of astigmatism and in ten eyes after photorefractive keratectomy. Best spherical corrected visual acuity in the astigmatic eyes was highly correlated with effective spherical aberration (r = -0.9527, P < .001). In the eyes that had photorefractive keratectomy, the effective spherical aberration was highly correlated with measured glare visual acuity (r = 0.875, P < .002). These results suggest that effective spherical aberration is a valuable topographic measure that provides information about the optical performance of aspheric corneas. PMID- 8450439 TI - Computerized videokeratographic analysis of corneal topographic changes induced by sutured and unsutured 4 mm scleral pocket incisions. AB - We used computerized videokeratography to analyze corneal topographical changes in 39 eyes of 39 patients who had phacoemulsification and posterior chamber lens implantation through 4 mm incisions. In one group of patients, the incisions were closed with a single vertical mattress suture; in the other group, no sutures were used. Computerized videokeratography was performed preoperatively and at one and five to six weeks postoperatively; corneal curvatures were assessed at radial distances of 0.75, 1.5, 2.5, and 3.5 mm along the 0-, 90-, 180-, and 270-degree semimeridians. At one week postoperatively, there was slightly more steepening along the 90- and 270-degree semimeridians (up to 0.9 diopters [D]) and slightly more flattening along the 0- and 180-degree semimeridians (up to 0.6 D) in the sutured group. At six weeks postoperatively, all mean semimeridional changes were less than 0.5 D. Computerized videokeratography demonstrated that sutured and unsutured 4 mm incisions induced clinically small corneal topographic changes and detected local variations in corneal curvature that may be due to sutures, cautery, and other operative factors. PMID- 8450440 TI - Effect of cataract wound incision size on acute changes in corneal topography. AB - A randomized prospective trial compared keratometric and visual outcomes for 196 patients receiving 3.2 mm, 5.0 mm, or 6.0 mm incisions for cataract removal and intraocular lens implantation. There were no statistically significant differences among the groups preoperatively or at one to two days or three to six months postoperatively in mean keratometric cylinder, no differences postoperatively in surgically induced cylinder, and no differences in best corrected visual acuity. Significantly more (P < .01) 3.2 mm cases (75%) had uncorrected visual acuity of 20/40 or better at one to two days postoperatively than 5.0 mm (50%) or 6.0 mm cases (47%). Computer-assisted corneal topographic images were available for the last 56 patients enrolled. Patients receiving 3.2 mm incisions had significantly less wound-related flattening than other patients (P < .05) and tended to have fewer surgically induced changes in corneal shape overall. Changes identified by corneal topography were inconsistent with keratometrically assessed cylinder in 14 patients. PMID- 8450441 TI - Comparison of the accuracy of computerized videokeratography and keratometry for use in intraocular lens calculations. AB - We compared the accuracy of keratometry and computerized videokeratography (CVK) for use in intraocular lens calculations. We studied 48 eyes of 45 patients having phacoemulsification and posterior chamber lens implantation. Computerized videokeratography was performed with the EyeSys Corneal Analysis System (ECAS). Using the SRK II, SRK/T, and Holladay formulas, we evaluated predictive accuracy calculated with keratometric values and four values derived from ECAS measurements. For each formula, the use of one of the CVK parameters resulted in lower mean absolute errors between actual and predicted postoperative refractive errors and higher percentages of cases with power prediction errors < 0.5 and < 1.0 diopters. Computerized videokeratography may provide a more accurate corneal curvature value than keratometry for use in intraocular lens calculations. PMID- 8450442 TI - Flattening of central corneal curvature with intrastromal corneal rings of increasing thickness: an eye-bank eye study. AB - Intrastromal Corneal Rings (ICRs) have been demonstrated to flatten human corneas when implanted into peripheral intrastromal corneal channels. To study the flattening effect, ICRs of increasing thickness, 0.26, 0.31, 0.36, 0.41, and 0.46 mm, were placed into oversized (approximately 70% depth) intrastromal channels in 38 eye-bank eyes. Each of 33 eyes received one ICR; the mean change in dioptric data was obtained for four meridians using an intraoperative photokeratoscope. Intrastromal corneal rings of increasing thickness resulted in corneal flattening of 3.8 +/- 1.1, 4.9 +/- 0.6, 5.2 +/- 1.1, 5.3 +/- 1.9, and 7.3 +/- 1.6 diopters, respectively, for keratoscope mire 2. One of each size ICR was placed into one of five additional eye-bank eyes; the degree of flattening measured by laser holographic interferometry was 1.8, 2.9, 5.5, 4.7, and 10.1 diopters, respectively, for the central 6 mm corneal zone. These results indicate that the ICR provides a fairly linear flattening relationship over the range of thicknesses tested. Additionally, laser holographic interferometry wave unit maps of preoperative and postoperative corneas demonstrated that the ICR tends to preserve positive corneal asphericity if present preoperatively. PMID- 8450443 TI - Intraoperative raster photogrammetry--the PAR Corneal Topography System. AB - The PAR Corneal Topography System (CTS) is a computer-driven corneal imaging system that uses close-range raster photogrammetry to measure and produce a topographic map of the corneal surface. The CTS determines distortion in a projected two-dimensional grid. Unlike Placido-disc-based videokeratoscopes, the PAR CTS produces a true topographic map (elevation map) and requires neither a smooth reflective surface nor precise spatial alignment for accurate imaging. Because the system uses two noncoaxial optical paths, it can be integrated into other optical devices. A modified CTS was integrated into an experimental erbium: YAG photoablative laser. The CTS successfully imaged corneas before, after, and during laser photoablation. Its ability to image nonreflective surfaces and to be integrated into other optical systems may make it suitable for intraoperative refractive monitoring. PMID- 8450444 TI - Preliminary results of a new intraoperative corneal topography technique. AB - We describe a new technique for measuring corneal topography intraoperatively and present preliminary results obtained with a prototype instrument. The technique is based on projected-fringe contouring and uses phase-shifting algorithms. Color coded true topographic maps, obtained during penetrating keratoplasty on human and cadaver eyes, are presented. PMID- 8450445 TI - Clinical evaluation of corneal topography. AB - Topographic mapping of the cornea has progressed markedly in the past few years with many improvements in computer hardware and software. This diagnostic technique, commonly referred to as computer-assisted videokeratography (CAVK), is performed with one of the corneal topography machines currently available. Many anterior segment surgeons use corneal topography in planning and monitoring their cataract and refractive surgery. Because of increased interest in this area, several surgeons were asked to comment on the role computer-assisted corneal topographic analysis plays in their practice of cataract and refractive surgery. They were asked what they felt were the best methods for measuring and analyzing corneal irregularities and how corneal topography should be used in cases of cataracts with astigmatism and in planning myopia and astigmatism surgery. PMID- 8450446 TI - Effect of nonsteroidal anti-inflammatory drugs on withdrawal responses in guinea pig ileum after a brief exposure to morphine. AB - The inhibition mechanism of nonsteroidal anti-inflammatory drugs (NSAIDs) on withdrawal response was examined in vitro. Naloxone elicited a strong contraction in the isolated guinea pig ileum after a 5-min exposure of the tissue to morphine. The contraction was inhibited by aspirin, indomethacin and salicylic acid, administered concomitantly to morphine or 1 min before the opioid antagonist. The short contact time of NSAIDs with the isolated preparations seems to indicate that mechanisms other than inhibition of prostaglandins synthesis are implicated in this action. NSAIDs depressed the ileum contraction to naloxone after stimulation of the tissue with cholecystokinin, when injected into the bath 1 min before the peptide. The contraction to naloxone after exposure to indirect excitatory peptides was very similar to withdrawal contraction. After maximal ileum stimulation with prostaglandin E1, naloxone induced a strong contraction indicating that this substance activates the opioid system, as occurs with cholecystokinin. NSAIDs, at concentrations that inhibit naloxone-induced contractions, did not depress the maximal contracture to cholecystokinin and prostaglandin E1, but inhibited the submaximal one. These results suggest that the inhibition of withdrawal contraction by NSAIDs in acute dependence is due mainly to their ability to block the contraction caused by substances whose action is neuronally mediated, which are released to counteract the opioid action. Prostaglandin E1 may be part of this system of action and reaction. PMID- 8450447 TI - Adenosine-stimulated contraction in nonpregnant guinea pig myometrium does not involve cyclooxygenase. AB - Cyclooxygenase products are thought to mediate adenosine-stimulated contraction of nonpregnant myometrium. We have examined the effects of the cyclooxygenase inhibitors, indomethacin and meclofenamate, upon adenosine-stimulated contractions in isolated, endometrium-free strips of uterine smooth muscle from virgin guinea pigs. Indomethacin (30 microM) had no effect on adenosine-induced contractions; addition of meclofenamate at 30 microM, however, rapidly and reversibly blocked contractions in response to adenosine, yet had no effect upon acetylcholine-stimulated contractions. Application of prostaglandin F2 alpha at a final concentration of 1.1 microM elicited contractions in indomethacin-treated (but not meclofenamate-treated) tissues. The adenosine receptor antagonist, 8-(p sulfophenyl)theophylline, interfered with adenosine-mediated contractions when present at a final concentration of 100 microM, confirming the presence of extracellular binding sites for the purine on the smooth muscle. Treatment of muscle strips with either of the adenosine uptake blockers, dipyridamole or S-(p nitrobenzyl)-6-thio-guanosine, resulted in dramatic reductions in adenosine stimulated contractions, findings consistent with an additional, intracellular site of action of adenosine in uterine smooth muscle. These results suggest that, in contrast to findings in intact strips of whole uterine tissue, cyclooxygenase activity is not required for adenosine-stimulated contraction in isolated myometrium from nonpregnant guinea pig. It also is suggested that the nonsteroidal anti-inflammatory compound, meclofenamate, may interfere with the binding of another (non-cyclooxygenase) product of arachidonic acid metabolism. PMID- 8450449 TI - Acute tolerance to triazolam during continuous and step infusions: estimation of the effect offset rate constant. AB - Although acute tolerance to selected effects of many benzodiazepines is known to occur, acute tolerance to triazolam has not been documented even in studies that have included pharmacodynamic modeling. The purpose of this investigation was to determine whether acute tolerance to triazolam occurs in humans. Intravenous bolus doses of triazolam were used to individualize two subsequent intravenous infusions: one to achieve and maintain a constant triazolam concentration and one to achieve a series of incremental steady-state concentrations; a placebo treatment was also included. Ten healthy men completed the four single-dose treatments. Serial blood sampling and psychomotor and memory testing were done. In the constant infusion treatment, mean performance impairment was greatest at 1 h and then decreased rapidly despite maintenance of a mean triazolam concentration of 2.48 ng/ml for 9 h. Neither learning nor changes in free concentration account for the observations. Additionally, data from the step infusion treatment indicate that the triazolam effect-concentration relationship after a single dose can be altered by rate of administration. Because tolerance develops, the administration of drug in small increments results in an increased effect at a lower concentration, with a blunted maximal response. Furthermore, our data suggest intersubject variability in the rate of development of acute tolerance. Patients who develop tolerance more slowly would experience a longer duration of effect. Further study regarding the rate of development of tolerance to specific effects and in different patient populations is warranted. PMID- 8450448 TI - Pharmacological profile of FR139317, a novel, potent endothelin ETA receptor antagonist. AB - The effects of FR139317 on the cardiovascular system were investigated in cultured cells, isolated organs and whole animals. FR139317 inhibited the specific binding of [125]endothelin(ET)-1 to porcine aortic microsomes in a concentration-dependent, monophasic fashion with an IC50 of 0.53 nM. In contrast, FR139317 showed low affinity for [125I]ET-1 specific binding sites in porcine kidney (IC50, 4.7 microM). In isolated rabbit aorta, FR139317 shifted the ET-1 induced concentration-contractile response curve to the right with a pA2 value of 7.2 and lacked agonist activity. A single (i.v.) bolus dose of FR139317 completely inhibited the pressor response to ET-1 in vivo, but had no effect on the initial depressor response in conscious normotensive rats. These data indicate that FR139317 is a potent, highly specific ETA receptor antagonist. In addition, FR139317 also inhibited ET-1 induced [3H]thymidine incorporation in cultured vascular smooth muscle cells from rat aorta (IC50, 4.1 nM), suggesting that ET-1-induced mitogenesis is mediated only by the ETA receptor. FR139317 could become a useful tool for investigating the physiological and pharmacological actions of ET. PMID- 8450450 TI - Role of lipid peroxidation in tert-butylhydroperoxide-induced inhibition of endothelial cell calcium signaling. AB - The potential of lipid peroxidation in inhibition of Ca++ signaling by the membrane-permeant oxidant, tertiary butylhydroperoxide (tert-buOOH), was investigated in calf pulmonary vascular endothelial cells. The oxidant dose dependently increased lipid peroxidation between concentrations of 10(-5) and 10( 3) M, with an ED50 of approximately 0.05 mM. In addition, the effect of tert buOOH was time-dependent through the experimental period (3 h). Preincubation of cells with the 21-amino-steroid compound, 21-[4-(5,6-bis(diethylamino)-2 pyridinyl)-1-piperazinyl]-16 alpha-methyl-pregna-1,4,9(11)-triene-3,20-dione hydrochloride (U74500A), reduced tert-buOOH-induced lipid peroxidation to undetectable levels. The effect of U74500A was dose dependent with an IC50 of approximately 10(-6) M. Brief incubation of cells with the aminosteroid resulted in greater than 90% inhibition of lipid peroxidation during subsequent 2-h incubations with tert-buOOH and addition of U74500A during treatment of cells with tert-buOOH halted further lipid peroxidation. In contrast, the iron containing moiety, hemin, potentiated the effect of tert-buOOH on lipid peroxidation. The ED50 of hemin was approximately 10(-6) M when cells were preincubated with this agent before treatment with tert-buOOH. The potentiating effect of hemin was time-dependent and reached a near maximum upon incubation of cells for 1 h before tert-buOOH. Preincubation of cells with U74500A before treatment with hemin and tert-buOOH decreased lipid peroxidation by 75%. Ca++ signaling was monitored in-cells loaded with the Ca(++)-sensitive fluorescent indicator, fura-2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450451 TI - Aminohydroxybutane bisphosphonate and clenbuterol prevent bone changes and retard muscle atrophy respectively in tail-suspended rats. AB - Hind-limb unloading by tail suspension of rats, an established model of simulated microgravity, was used to examine the efficacy of aminohydroxybutane bisphosphonate (AHBuBP) and clenbuterol in preventing bone loss and muscle atrophy, respectively. Male Sprague-Dawley rats (299-372 g) were randomized into six groups of six: 1) unsuspended, saline, 2) unsuspended, saline, pair fed with group 3, 3) suspended, saline, 4) suspended, 0.03 mg/kg/day x 2 of AHBuBP, 5) suspended, 0.3 mg/kg/day x 2 of AHBuBP and 6) suspended, 0.3 mg/kg/day x 2 of AHBuBP + clenbuterol (0.5 mg/kg/day i.p. x 6, then 1 mg/kg/day i.p. x 6). Animals in groups 3 to 6 were tail suspended for 14 days from a system of double pulleys and allowed free mobility with their hind limbs unloaded. On days -2 and -1, before suspension on day 0, all rats received a single s.c. injection of either 2 ml/kg of normal saline (vehicle) or AHBuBP. All rats were tested for exercise tolerance before day -2 and on day 10, and grip strength before day -2 and on day 13. On day 14, the rats were euthanized and their humeri, tibias and femurs analyzed in vitro for bone density (by single-photon absorptiometry), strength and stiffness (by 3-point bending). Muscles were analyzed for weight, protein concentration and enzyme activity. Pair feeding had no effect other than on food consumption and body weight. AHBuBP caused a dose-dependent increase in bone density in humeri, tibias and femurs, even in tail-suspended rats, relative to control unsuspended animals, with no significant difference in bone strength or stiffness between AHBuBP groups and unsuspended animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450452 TI - Comparison of antidote protection against soman by pyridostigmine, HI-6 and acetylcholinesterase. AB - Carbamate, oxime and enzyme scavenger approaches to protection against the highly toxic organophosphorus compound, soman, were compared by using the most prominent example of each type of antidote. Pyridostigmine in combination with atropine, HI 6 [1-(2-(hydroxyimino)methyl))pyridinium-2-(4-(aminocarbonyl)p yridinium) dimethylether] in combination with atropine and fetal bovine serum acetylcholinesterase (FBS-AChE) without atropine were used as examples of oxime, carbamate and enzyme scavenger antidotes, respectively. Each antidotal regimen produced approximately equal maximal protection against the lethal effects of 952 to 1169 nmol/kg (LD50, 8-10) of soman in mice whose carboxylesterase had been inhibited with 2-(o-cresyl)-4H-1:3:2-benzodioxaphosphorin-2-oxide. FBS-AChE was much better than either pyridostigmine-atropine or HI-6-atropine in reducing postexposure incapacitation from soman as measured by lacrimation, motor dysfunction, activity level and the inverted screen test. A lower dose of pyridostigmine (566 nmol/kg) or FBS-AChE (1150 nmol/kg) was required to protect against 968 nmol/kg (LD50, 8) of soman than was required for HI-6 (200,000 nmol/kg). Inasmuch as the in vivo biological half-life of FBS-AChE (1550 min) was much greater than the biological half-lives of pyridostigmine (48 min) or HI-6 (11 min), the ability of FBS-AChE to produce better protection against the postexposure incapacitation from soman suggests that it should be considered as an alternative to either pyridostigmine-atropine or HI-6-atropine antidotal regimens. PMID- 8450453 TI - Attenuation and reversal of morphine tolerance by the competitive N-methyl-D aspartate receptor antagonist, LY274614. AB - The ability of a competitive (LY274614; (+-)-6-phosphonomethyl decahydroisoquinolin-3-carboxylic acid) and a noncompetitive (MK801; [(+)-5 methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine hydrogen maleate) N methyl-D-aspartate receptor antagonist to modulate the development of tolerance to morphine's antinociceptive (analgesic) effects was assessed by using hot-plate latency in rats. Concurrent treatment with LY274614 or MK801 by continuous s.c. infusion significantly attenuated the development of morphine tolerance produced by twice daily injections of morphine (10 mg/kg s.c.). This attenuation of morphine tolerance by LY274614 was dose-dependent, 12 or 24 mg/kg/24 hr s.c. infusion). Additionally, animals tested 1 week after the discontinuation of all drug treatments were observed to retain their analgesic sensitivity to morphine, whereas control animals remained relatively tolerant. These results suggest that LY274614 and MK801 do not alter the expression of tolerance but actually modify the development of morphine tolerance. Morphine-tolerant animals infused with LY274614 for 7 days regained their analgesic sensitivity to morphine. Furthermore, LY274614 also reversed the development of tolerance and restored morphine sensitivity in tolerant animals that continued to receive morphine. The demonstration that LY274614 can prevent and reverse the development of morphine tolerance without reducing the analgesic response suggests that the adaptive system involved in the development and maintenance of tolerance requires a functional N-methyl-D-aspartate receptor. LY274614 lacks the phencyclidine-like side effects seen with MK801, and this may favor the clinical development of this competitive N-methyl-D-aspartate receptor antagonist as an adjunct for patients receiving chronic opioids for pain management. PMID- 8450454 TI - Analysis of the inhibitory effects of DuP 753 and EXP 3174 on responses to angiotensin II in the feline hindquarters vascular bed. AB - The effects of DuP 753 and EXP 3174, nonpeptide angiotensin II type 1 antagonists, on responses to angiotensin II were investigated in the hindquarters vascular bed of the cat. Under constant flow conditions, injections of angiotensin II into the hindquarters perfusion circuit elicited dose-dependent increases in perfusion pressure. Responses to the peptide were stable with respect to time, did not exhibit tachyphylaxis, and 2-n-butyl-4-chloro-5 hydroxymethyl-1-[2'-(1H-tetrazol-5-yl)biph eny l-4-yl]methyl]methyl]imidazole (DuP 753) in doses of 1 and 2.5 mg/kg decreased vasoconstrictor responses to angiotensin II in a competitive manner, with a longer duration of action at the higher dose. DuP 753 had no significant effect on vasoconstrictor responses to vasopressin, norepinephrine, neuropeptide Y or 11 alpha,6 alpha-epoxymethano-9 alpha,11 alpha-dideoxy-prostaglandin F2 alpha, on biphasic responses to endothelin-1, or on vasodilator responses to acetylcholine. 2-n-Butyl-4-chloro-1 [2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]im idazole-5-carboxylic acid (EXP 3174) also decreased responses to angiotensin II without altering responses to norepinephrine, vasopressin, U46619 or endothelin-1. The inhibitory effect of EXP 3174 was surmountable; however, large doses of angiotensin II were required, and the blockade was long in duration. The effects of DuP 753 and EXP 3174 on responses to angiotensin II and angiotensin III were similar, and when EXP 3174 was administered in doses of 0.1 and 0.05 mg/kg i.v., the blockade was overcome and the dose-response curves for angiotensin II were shifted to the right in a parallel manner.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450455 TI - Potassium channel blocking properties of propafenone in rabbit atrial myocytes. AB - Propafenone, a class 1c antiarrhythmic agent, is known to be a potent blocker of voltage-dependent sodium channels; however, several clinical actions of the drug point toward possible potassium channel blocking capability. The present experiments were designed to assess the extent and potential mechanisms of potassium channel blocking properties of propafenone. Whole-cell voltage-clamp techniques were used to define the actions of propafenone on the transient outward current (Ito), the delayed rectifier current (Ik) and the inward rectifier current (Ik1) in isolated rabbit atrial myocytes. Propafenone blocked all three currents, with the extent of blockade being independent of test potential During depolarizing voltage steps, block of Ito and Ik developed as an exponential function of time, consistent with time-dependent open channel blockade. The rate constant of block onset was concentration dependent. The inactivation of Ito was a monoexponential function of time under control conditions, with a time constant averaging 19.1 +/- 1.3 msec (mean +/- S.E.) at +10 mV. Propafenone accelerated Ito inactivation, resulting in a biexponential process having time constants of 5.1 +/- 0.9 (P < .001 vs. control) and 23.5 +/- 2.0 msec (P = N.S. vs. control) at 5 microM and 3.4 +/- 0.5 (P < .001 vs. control) and 28.5 +/- 4.3 msec (P = N.S.) at 10 microM concentrations, respectively. The rapid phase inactivation time constants were of the same order as time constants for the onset of block (3.1 +/- 0.6 and 1.8 +/- 0.3 msec at 5 and 10 microM respectively), suggesting that the acceleration of Ito inactivation was due to open channel block by the drug. The IC50 for blockade was substantially less for effects on Ik (0.76 microM; 95% confidence limits 0.44 1.30 microM) than for Ito (5.91 microM; 95% confidence limits 4.19-8.33 microM) or Ik1 (7.10; 5.24-9.61 microM). We conclude that 1) propafenone is an efficacious potassium channel blocker; 2) propafenone blockade of time-dependent potassium currents is open-state dependent; and 3) propafenone block of potassium currents is relatively selective for Ik. PMID- 8450456 TI - Cholinergic and anticholinergic drug effects on survival during hypoxia: significant gender differences. AB - We examined central and peripheral components of cholinergic drug protection against hypoxia in male and female mice. Survival times were measured in groups of control and treated (i.p. injection) animals exposed to hypoxia (5% O2/95% N2). Body temperatures were also measured in separate groups of normoxic control and treated animals. Control (NaCl) animals of both sexes survived only 3.5 and 3.7 min of hypoxia. After physostigmine (0.2 mg/kg), however, significantly more females (82.4%) than males (40.5%) survived 35 to 60 min of hypoxia, although physostigmine hypothermia was equal in both sexes. Pilocarpine (5 mg/kg) also produced a gender difference (female > male) in survival, despite equal hypothermia. Hypothermia after neostigmine (0.2 mg/kg) was equal in males and females, yet neither sex survived longer than controls. The protective and hypothermic effects of physostigmine were blocked by atropine sulphate (5 mg/kg). In contrast, atropine methylnitrate (2 mg/kg) did not block physostigmine hypothermia in either sex, but markedly decreased physostigmine's protective effect in females. Beside the significant gender differences in physostigmine and pilocarpine protection, the results show that hypothermia alone is not responsible for protection or for the gender difference. Survival prolongation in males appears to depend solely on physostigmine's central actions. In females, peripheral actions (e.g., hormone release from pituitary and ovary) may contribute to protection and to the gender difference. PMID- 8450457 TI - Direct evidence for selective involvement of aortic baroreceptors in ethanol induced impairment of baroreflex control of heart rate. AB - In a previous study, we have shown that ethanol reduced baroreflex control of heart rate (baroreflex sensitivity, BRS) in conscious sham-operated (SO) rats, but not in aortic barodenervated rats, which suggested, by elimination, a role for aortic baroreceptors in the depressant effect of ethanol on BRS. The present study sought direct evidence to support the hypothesis that aortic baroreceptors are selectively influenced by ethanol. The effect of ethanol on BRS measured by evoked increments (phenylephrine) and decrements (nitroprusside) in blood pressure was studied in conscious unrestrained carotid barodenervated (CBD) and SO rats. The experiments were carried out on 2 consecutive days in the same rats and used phenylephrine on one day and nitroprusside on the other. Compared to sham operation, CBD caused an acute rise in mean arterial pressure and heart rate and a significant reduction in BRS. Two days later, mean arterial pressure and heart rate of conscious unrestrained CBD rats subsided to control levels, whereas baroreflex-mediated bradycardic and tachycardic responses were 65 and 35%, respectively, of control values. Administration of ethanol (1 g/kg) produced similar brief pressor and bradycardic responses in CBD and SO rats. In spite of a significantly lower BRS in CBD as compared to SO rats, ethanol (1 g/kg) caused a significant (P < .05) and comparable attenuation of BRS measured by the response to phenylephrine in CBD and SO rats (30% vs. 38%). In contrast, ethanol caused slight nonsignificant reductions in BRS measured by the response to nitroprusside in CBD and SO rats. Blood ethanol concentrations were similar in both groups of rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450458 TI - Actions of A-75200, a novel catecholamine uptake inhibitor, on norepinephrine uptake and release from bovine adrenal chromaffin cells. AB - The balance between catecholamine (CA) release and reuptake is closely regulated and determines the effective level of transmitter at the synaptic cleft. Drugs that block CA uptake have potential utility as antidepressant medications. One such drug is racemic (+/-)-(1' R*,3R*)-3-phenyl-1-[1',2',3',4'-tetrahydro-5',6'- methylenedioxy-1'-naphthalenyl-methyl]-pyrrolidine methanesulfonate (A-7500), a novel polycyclic compound developed at Abbott Laboratories. This compound is known to bind to CA transporters in the central nervous system, however, its effects on an intact neurosecretory system have not been studied. In this regard, norepinephrine (NE) release from bovine adrenal chromaffin cells (BACC) is a classic model system for CA release and is an excellent system in which to examine the effects of drugs which modulate neurotransmitter release. We compared the effects of A-75200 and its two constituent enantiomers, A-74111 and A-74112, to the effects of three well-characterized uptake inhibitors, desipramine (DMI), nomifensine and cocaine. We found that the Abbott compounds inhibit [3H]norepinephrine ([3H]NE) uptake with an EC50 comparable to cocaine. In addition, unlike nomifensine and cocaine, these compounds inhibited nicotine- and K(+)-stimulated NE release, whereas histamine-stimulated release was preserved. Thus, the Abbott compounds block the effects on secretion of two agonists (nicotine and K+) which depend on a depolarization-dependent influx of extracellular calcium. We conclude that in addition to blocking NE uptake by inhibiting the NE transporter, the Abbott compounds may modulate peripheral NE release by inhibiting calcium flux through voltage-gated channels. This study demonstrates the utility of bovine adrenal chromaffin cells for preclinical trials of drugs that affect catecholaminergic neurotransmission. PMID- 8450459 TI - Acute effects of triazolam and lorazepam on human learning, performance and subject ratings. AB - Triazolam (0,0.125, 0.25, 0.5, and 0.75 mg/70 kg) and lorazepam (0, 1, 2, 4 and 6 mg/70 kg) were compared in eight healthy men by using a double-blind, crossover design. Triazolam was chosen for study to examine experimentally whether it produces greater behavioral impairment than other benzodiazepines as reported previously. Lorazepam was chosen as the comparison drug because of its well documented behavioral effects and because it has a short metabolic half-life and no active metabolite, which eliminates the possible confounding effects of drug accumulation. Drug effects were assessed before and every 30 min for 8 hr after drug administration. Learning was chosen for study because it is a fundamental component of more complex behavioral processes such as recall, and benzodiazepines are known to disrupt learning. A psychomotor task and subject rating scales, assessing drug effects and abuse potential, were also included to provide a more comprehensive comparison of these compounds. Triazolam and lorazepam dose-dependently disrupted learning and psychomotor performance and increased subject ratings of sedation to a comparable degree. These findings do not support allegations that triazolam produces greater behavioral impairment than other commonly used benzodiazepines. PMID- 8450460 TI - Effects of ATP and related nucleotides on the tone of isolated rat mesenteric resistance arteries. AB - The relationship between ecto-ATPase activity and the vasoactive effect of ATP is unclear. Previously we have characterized the ectonucleoside triphosphatase activity of isolated rat mesenteric small arteries and now characterize the effect of nucleotides on the tone of these arteries. In resting arteries, ATP caused concentration-dependent contractions that were transient and could not be reproduced within 2 h. Transient contractions in response to ATP also were elicited in arteries precontracted with norepinephrine, but the potency of ATP was increased and responses to repeated stimulations could be obtained. Contractions were followed by relaxation. The response to ATP was unaffected by 100 microM theophylline, 1 microM propranolol or removal of the endothelium. Transient contractions followed by relaxation were caused also by ADP, 2-methyl thio-ATP (2meSATP) and alpha, beta-methylene-ATP (alpha, beta-meATP). UTP caused sustained contractions, whereas GTP and ITP had little effect. The rank order of potency (alpha, beta-,mATP > ATP > ADP) suggested that P2x purinoceptors were responsible for the contractions, whereas the rank order of potency for the relaxation (alpha, beta-meATP > or = ATP > 2meSATP) was not consistent with the relaxation being mediated by P2Y purinoceptors as defined originally. Desensitization of the contractile response to ATP by alpha, beta-meATP was variable. In contrast, inhibition of the response to ATP was obtained consistently and dose-dependently with GTP. PMID- 8450461 TI - Discriminative stimulus effects of ethanol: effect of training dose on the substitution of N-methyl-D-aspartate antagonists. AB - The ethanol-like discriminative stimulus effects of N-methyl-D-aspartate (NMDA) antagonists that act at the NMDA recognition site [(D)-4-(3-phosphonoprop-2 enyl)piperazine-2-carboxylic acid (CPPene) and cis-4-phosphonomethyl-2-piperidine carboxylic acid] or within the NMDA associated cation channel [phencyclidine (PCP) and dizocilpine] were evaluated in rats trained to discriminate ethanol or PCP from vehicle in a two-lever discrimination procedure. Three groups of rats were trained to discriminate 1.0, 1.5 or 2.0 g/kg of ethanol from water and one group was trained to discriminate 1.5 mg/kg of PCP from saline. In the ethanol trained groups, both PCP (1.0-5.6 mg/kg; i.p.) and dizocilpine (0.03-0.3 mg/kg; i.p.) completely substituted for ethanol in every rat tested, although the dizocilpine resulted in only partial substitution in rats trained to discriminate 1.0 g/kg of ethanol. As the training dose of ethanol increased, the potency of PCP and dizocilpine to substitute for ethanol increased. In contrast, CPPene (1 17 mg/kg; i.p.) and cis-4-phosphonomethyl-2-piperidine carboxylic acid (5.6-17 mg/kg; i.p.) resulted in partial substitution for ethanol, with lower amounts of ethanol-appropriate responding as the training dose of ethanol increased. These data indicate that uncompetitive antagonism of NMDA neurotransmission at sites within the cation channel produce discriminative stimulus effects that are similar to those of ethanol, particularly to higher ethanol doses. Neither ethanol (0.5-1.5 g/kg; i.p.) nor CPPene (5.6 and 10 mg/kg) completely substituted for the discriminative effects of PCP. The asymmetrical generalizations between ethanol and PCP are discussed in terms of the mixed discriminative effects of ethanol. PMID- 8450462 TI - Effects of neuropeptide Y, peptide YY and sigma ligands on ion transport in mouse jejunum. AB - The effects of putative sigma ligands and two neuropeptides on intestinal ion transport were evaluated in isolated sheets of whole mouse jejunum mounted in Ussing flux chambers. Serosal administration of neuropeptide Y (NPY), peptide YY (PYY), (+)-N-cyclopropylmethyl-N-methyl-1,4- diphenyl-1-ethyl-but-3-en-1-ylamine hydrochloride (JO 1784), di(ortho-tolyl)guanidine (DTG) and (+)- or (-)-N-allyl normetazocine (NANM) produced concentration-related decreases in short-circuit current (Isc) without changes in tissue conductance. Although NPY and PYY were active in nanomolar concentrations, JO 1784, DTG and (+)- and (-)-NANM were active in micromolar concentrations; the rank order of potency in inhibiting Isc was PYY > NPY >> JO 1784 = (-)-N- cyclopropylmethyl-N-methyl-1,4-diphenyl-1-ethyl but-3-en-1-ylamine hydrochloride > DTG > (+)-NANM = (-)-NANM. Serosal application of tetrodotoxin effectively blocked the decrease in Isc associated with all of the ligands tested. The activity of the serosally applied ligands was blocked by prior application of chlorisondamine, a ganglionic blocker. The effects of JO 1784 and NPY were evaluated using antagonists of several receptor types. Although application of serosal haloperidol had no effect alone up to concentrations of 1 microM, this compound produced a rightward displacement in both the NPY and JO 1784 concentration-effect curves. In contrast, sulpiride, SCH-23390, naloxone, yohimbine and prazosin failed to antagonize the effects of NPY or JO 1784.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450463 TI - Interaction between thromboxane A2 and angiotensin II in postischemic renal vasoconstriction in dogs. AB - The kidney responds to periods of ischemia with vasoconstriction and a decrease in glomerular filtration rate (GFR) on reperfusion. The mediators of this response have not been fully identified. In this study, we examined the contribution of angiotensin II (AII), thromboxane A2 (TXA2) and the interaction between them to this response. Anesthetized dogs were subjected to 30 min of clamping of both renal arteries. Renal hemodynamics and function were followed from 60 min before and for 105 min after clamping. Dogs were divided into salt depleted (AII-stimulated) and captopril-treated (AII-inhibited) groups. Each group included dogs that received either the TXA2 synthase inhibitor CGS 13080 or its vehicle (controls) starting 30 min before renal artery clamping and lasting to the end of the experiment. In captopril-treated control dogs, 30 min of ischemia induced a 25% fall in renal blood flow (RBF). GFR initially fell by 75%, but recovered to 64% of base-line value 60 to 90 min after release of the clamp. In captopril-treated dogs, CGS 13080 prevented the fall in RBF, but the GFR response was similar to vehicle-treated dogs. In control dogs, both GFR and RBF responses were enhanced in salt-depleted compared with captopril-treated dogs; the decrease in RBF (44%) was greater, and the recovery in GFR, which fell by 89%, less. In salt-depleted, CGS 13080-treated dogs, the 30% fall in RBF was less than its control, but greater than dogs treated with captopril and CGS 13080. The change in GFR was similar to the other groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450464 TI - Alteration of rat hepatic insulin metabolism by glyburide and glipizide. AB - The sulfonylurea class of compounds has demonstrated its effectiveness in treating non-insulin-dependent diabetes mellitus, although the exact mechanisms of action are still not fully defined. Clinical studies have suggested the action may be at least in part due to alterations of insulin's effect on liver. We have examined the effects of glyburide and glipizide on insulin metabolism in isolated hepatocytes and perfused livers. Our studies show that both drugs increase insulin binding to hepatocyte, but only glyburide-treated animals exhibit a concomitant increase in degradation. Studies with recycling perfused liver agreed with these results, with glyburide treatment causing a significantly more rapid clearance than control or glipizide treatment. Single-pass perfusion studies showed significantly less insulin retained by glipizide-treated animals as compared to control- and glyburide-treated animals. Further, hepatocytes from glipizide-treated animals required higher concentrations of insulin to achieve the same stimulation of amino acid transport (as measured by aminoisobutyric acid uptake) as in control- and glyburide-treated animals, suggesting that the altered processing affects insulin's action. Taken together, these studies demonstrate alterations in liver insulin metabolism that may explain clinical differences identified in these two drugs. PMID- 8450465 TI - In vivo reversal of doxorubicin resistance by a new tiapamil analog Ro11-2933. AB - The effectiveness of a calcium antagonist analog Ro11-2933 to modulate doxorubicin (DOX) response in DOX-sensitive (WT) and -resistant (DOXr, 200-fold) cell lines was investigated and compared to verapamil (VP) in vitro and in vivo in rats bearing mammary carcinoma using equivalent nontoxic doses. In vitro exposure to a nontoxic concentration of Ro11-2933 (2 microM) normalizes the DOX accumulation defect observed in DOXr cells, increases DOX-induced DNA single strand breaks and effectively sensitizes DOXr cells to DOX. Ten microM VP was required to obtain an effect equivalent to that seen with 2 microM Ro11-2933. Intravenous administration of DOX at 5 mg/kg to the rat bearing the DOXr tumors has no significant therapeutic effect on tumor growth (P > .5), whereas it was found effective in inhibiting the growth of WT tumors (P < .05). Ro11-2933 or VP administered alone has no significant effect on tumor growth as compared to a saline-treated group (P > .1). Combination of Ro11-2933 with DOX effectively inhibits DOXr tumor growth as compared to DOX alone. Combination of DOX with VP was found less effective than Ro11-2933 and the results were not statistically significant from DOX treatment alone (P > .5). Our data demonstrate that Ro11 2933 is well tolerated after i.v. administration and an effective modulator of DOX resistance in a solid tumor model. PMID- 8450466 TI - Acute effects of nicotine on rat mesenteric vasculature and tail artery. AB - The effect of nicotine on adrenergic and sensory nerves was examined in tail artery ring segments and isolated perfused mesenteric vascular bed. Nicotine by itself (3 x 10(-5) and 3 x 10(-4) M) had no vasoconstrictor effect on the perfused mesentery. However, in the presence of guanethidine (5 x 10(-6) M) and methoxamine (5 x 10(-6) M), nicotine (5 x 10(-5) and 10(-4) M) caused vasodilation of 20 +/- 4 and 26 +/- 6%, respectively. The relaxation produced by nicotine was attenuated in the presence of capsaicin (3 x 10(-7) M) to desensitize sensory nerves. Higher concentrations of nicotine (3 x 10(-4) and 10( 3) M) also produced a relaxation of the mesenteric artery by 49 +/- 7 and 73 +/- 11%, respectively, an effect that was insensitive to capsaicin. The nicotinic antagonist hexamethonium (10(-5) M) blocked the relaxation produced by both low and high concentrations of nicotine. Removal of the endothelium by saponin (50 mg/ml) did not change the effect of nicotine, nor did the cyclooxygenase inhibitor indomethacin (10(-6) M). In tail artery ring segments, nicotine had no effect by itself. Nicotine (10(-5) to 10(-3) M) did not potentiate contractile responses evoked by transmural nerve stimulation, rather relaxation was produced with concentrations above 10(-4) M. These data suggest that at low concentrations nicotine activates capsaicin-sensitive sensory nerves via an action on nicotinic receptors. At higher concentrations nicotine relaxes vascular smooth muscle directly, an effect which is independent of sensory nerves.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450467 TI - Effect of arachidonic acid on twitch tension of the rat phrenic nerve-diaphragm. AB - Recent studies have demonstrated that unsaturated fatty acids are involved in the regulation of neuroeffector function. I have extended these studies by examining the effect of arachidonic acid on neuromuscular function in vitro using the rat phrenic nerve-diaphragm preparation. Arachidonic acid caused a time-and dose dependent reduction in indirectly stimulated twitch tension, but had no effect on directly stimulated twitch tension. Linoleic acid and linolenic acid also reduced indirectly stimulated twitch tension, whereas stearic acid, oleic acid and arachidic acid had no effect. None of three blockers of arachidonic acid metabolism, the cyclooxygenase inhibitor indomethacin, the lipoxygenase inhibitor nordihydroguaiaretic acid or the cytochrome P-450 inhibitor ketoconazole, altered the effect of arachidonic acid on twitch tension. The free radical scavenger superoxide dismutase eliminated the inhibitory effect of arachidonic acid on twitch tension, suggesting that superoxide anion played a role in arachidonic acid's action. PMID- 8450468 TI - Tone-dependent responses of 5-hydroxytryptamine in the feline pulmonary vascular bed are mediated by two different 5-hydroxytryptamine receptors. AB - Mechanisms to explain tone-dependent responses of the feline pulmonary vascular (PV) bed to 5-hydroxytryptamine (5-HT) were investigated in intact-chest, spontaneously breathing cats under conditions of controlled pulmonary blood flow and constant left atrial pressure. At low (resting) PV tone, intralobar injections of 5-HT produced dose-dependent vasoconstrictor (VC) responses which were significantly blocked by the selective 5-HT2 receptor antagonist ketanserin and enhanced by the cyclooxygenase inhibitor meclofenamate. When PV tone was increased with 9,11-dideoxy-9 alpha 11 alpha epoxymethano prostaglandin F2 alpha, intralobar injections of 5-HT produced vasodilator (VD) responses at low doses, biphasic VC/VD responses at midrange doses and predominant VC responses at high doses. The VC responses at elevated PV tone were dose dependent and antagonized by ketanserin. The VD responses were antagonized by the mixed 5-HT1, 5-HT2 receptor antagonist methysergide. Meclofenamate had no effect on VC or VD responses of 5-HT at elevated PV tone. At both low (resting) and elevated PV tone, 5-HT and the selective 5-HT2 receptor agonist alpha-methyl-5-HT produced greater VC responses than the selective 5-HT1 receptor agonist 5 carboxyaminotryptamine and the selective 5-HT3 receptor agonist 2-methyl-5-HT. At elevated PV tone, 5-carboxyaminotryptamine and 5-HT produced greater VD responses than alpha-me-5-HT and 2-methyl-5-HT. Compared to low (resting) PV tone, VC responses of 5-HT and alpha-methyl-5-HT were enhanced at elevated PV tone. These data support that 5-HT-induced VC responses at both low (resting) and elevated PV tone are mediated by 5-HT2 receptors and 5-HT-induced VD responses at elevated PV tone are mediated by "5-HT1-like" receptors. A change in PV tone may alter receptor availability, affinity or receptor-effector coupling. PMID- 8450469 TI - Cocaine-induced seizures and lethality appear to be associated with distinct central nervous system binding sites. AB - Cocaine use and abuse has increasingly been associated with toxic consequences such as seizures and death. This report describes an assessment of the relationship between these toxic effects and multiple cocaine binding sites in the brain. The results suggest that serotonin transporters may be associated with seizures induced by acute injections of cocaine and related drugs. Indeed, drug potency for binding at this site alone accounted for 78% of the variance (r = 0.88) in the potency of cocaine and related compounds for producing seizures. However, binding of cocaine-like drugs at sigma receptors or muscarinic M1 or M2 cholinergic receptors may attenuate the seizurgenic properties of these compounds. In contrast, dopamine transporters appear to be associated with lethality induced by cocaine and related drugs, with drug potency for binding at this site accounting for 56% of the variance (r = 0.75) in the potency of cocaine and related compounds for producing death. However, binding of cocaine-like drugs at muscarinic M1 and sigma receptors also appears to be significantly related to cocaine-induced lethality, with binding at these sites accounting for either an additional 31 or 27%, respectively, of the variance in potencies of cocaine and related drugs to produce death. These findings suggest that, although seizure initiation may depend primarily on affinity of cocaine and related compounds for binding sites associated with the serotonin transporter, the seizure-inducing properties of cocaine may ultimately depend on a final summation of its effects not only on serotonergic systems, but on muscarinic and sigma neuronal systems as well. Likewise, although apparently mediated by relatively distinct neuronal mechanisms, the lethal effects of cocaine and related compounds may depend on an interaction of effects at dopaminergic, muscarinic M1 and sigma receptor sites. PMID- 8450470 TI - Aminoalkylindole binding in rat cerebellum: selective displacement by natural and synthetic cannabinoids. AB - A binding assay for WIN 55212-2, an aminoalkylindole (AAI) with antinociceptive activity in rodents, is described. [3H]WIN 55212-2 bound to rat cerebellar membranes with a Kd of 2 nM and a maximum binding of 1.2 pmol/mg of protein. Specific binding in this filtration assay was greater than 90%, saturable, reversible, stereospecific, pH sensitive and heat labile. Binding was decreased by Na+, K+, Li+ and nonhydrolyzable analogs of GTP and increased by Mg++ and Ca++. The density of specific binding sites varied throughout the central nervous system with the highest found in the cerebellum, hippocampus and striatum and the lowest in the medulla/pons and spinal cord. The binding affinities of other AAIs for the WIN 55212-2 binding site correlated with their potencies for inhibiting neuronally stimulated contractions in the isolated mouse vas deferens. Of more than 60 compounds representing recognized neurotransmitter systems, only cannabinoids effectively inhibited binding. The effect of cannabinoids on AAI binding was consistent with competitive inhibition and suggests that AAI activity may be mediated in whole or in part by interaction with cannabinoid receptors. AAIs appear to represent a structurally novel class of compounds with which to study cannabinoid receptors. PMID- 8450471 TI - Induction of hypothermia as a model of 5-hydroxytryptamine1A receptor-mediated activity in the rat: a pharmacological characterization of the actions of novel agonists and antagonists. AB - In this study, we examined the localization of the 5-hydroxytryptamine (5-HT)1A receptors mediating hypothermia in the rat, evaluated the pharmacological specificity of this response and examined the influence of a series of novel 5 HT1A receptor ligands upon core temperature. Administered s.c., 8-hydroxy-(2-di-n propylamino)tetralin hydrobromide (8-OH-DPAT), an agonist at both pre- and postsynaptic 5-HT1A receptors, elicited pronounced hypothermia. In contrast, BMY 7378, which shows low efficacy at postsynaptic 5-HT1A receptors but high efficacy at presynaptic 5-HT1A receptors, elicited only mild hypothermia. Similarly, 8-OH DPAT was more efficacious than BMY 7378 in eliciting corticosterone secretion, a response mediated by postsynaptic 5-HT1A receptors, whereas BMY 7378 was as efficacious as 8-OH-DPAT in inhibiting striatal accumulation of 5 hydroxytryptophan, a response mediated by presynaptic 5-HT1A receptors. These data suggest, by analogy, that postsynaptic 5-HT1A receptors mediate hypothermia, an interpretation supported by the observation that destruction of central 5-HT neurons with 5,7-dihydroxytryptamine failed to reduce 8-OH-DPAT-induced hypothermia (DIH). Agonists at 5-HT1B, 5-HT1C, 5-HT2 and/or 5-HT3 receptors did not elicit hypothermia, and drugs releasing 5-HT elicited hyperthermia. In contrast, DIH was fully mimicked by the novel 5-HT1A receptors agonists, eltoprazine, WY 48,723, MDL 72832, tandospirone, S 14671, S 14506 and WY 50,324, whereas the novel partial agonist, zalospirone, was less efficacious. DIH was blocked by (-)-alprenolol, (+/-)-pindolol and the novel beta-blocker, (-) tertatolol, which also has high affinity for 5-HT1A receptors; in distinction, betaxolol and ICI 118,551, antagonists at beta-1 and beta-2 adrenoceptors, respectively, were inactive. Spiperone, NAN-190 and BMY 7378 also inhibited DIH whereas ritanserin, SCH 39166, raclopride and prazosin, antagonists at 5-HT2 receptors, D1 and D2 dopamine receptors and alpha-1 adrenoceptors, respectively, were inactive. The novel 5-HT1A antagonists, WAY 100,135, MDL 73005 EF and (very potently) SDZ 216-525 all blocked DIH. Potency for induction of hypothermia and inhibition of DIH correlated well with affinity for 5-HT1A binding sites. In conclusion, hypothermia is a highly specific and sensitive response to activation of postsynaptic 5-HT1A receptors. Furthermore, DIH is inhibited by their selective blockade. At postsynaptic 5-HT1A receptors mediating hypothermia, eltoprazine, WY 48,723, MDL 72832 and tandospirone are agonists, zalospirone is a partial agonist and (-)-tertatolol, WAY 100,135, MDL 73005 EF and SDZ 216-525 are antagonists. PMID- 8450472 TI - Involvement of renal dopamine synthesis in the diuretic effect of furosemide in normohydrated rats. AB - The present study was designed to investigate whether the modification of dopamine synthesis affects furosemide responses. Experiments were performed on pentobarbital-anesthetized rats. Basal urine flow was approximately 3 microliters/min-1/g-1 of kidney weight (k.w.); furosemide (0.2 mg/kg-1 i.v.) induced a rapid diuretic effect (19.3 +/- 1.4 microliters/min-1/g-1 of k.w.). The dopadecarboxilase inhibitor, benserazide (25 mg/kg-1 i.v.), reduced furosemide induced diuresis to 8.3 +/- 2.1 microliters/min-1/g-1 of k.w., whereas levo dihydroxyphenylalanine (L-dopa; 1 micrograms/kg-1/min-1 infused for 60 min) increased it to 41.4 +/- 6.1 microliters/min-1/g-1 of k.w. Natriuretic response and fractional Na+ excretion induced by furosemide were significantly lower in benserazide-treated and higher in L-dopa-treated animals. Urine dopamine (DA) excretion was enhanced by furosemide from 0.44 +/- 0.05 to 0.98 +/- 0.22 ng/min 1/g-1 of k.w. and was markedly reduced in benserazide-pretreated animals, whereas both basal DA excretion and that induced by furosemide were increased significantly during L-dopa infusion. However, in benserazide- or L-dopa-treated animals, basal urine flow was not different from the control group. Urine furosemide excretion was reduced by 60% by benserazide treatment and increased by 62% during L-dopa infusion. The results are consistent with the suggestion that although endogenous DA is apparently unimportant in the maintenance of basal urine output, it is involved in furosemide-induced diuresis. The diuretic response can be altered by acute administration of substances that affect dopamine synthesis. PMID- 8450473 TI - Binding and function of a potent new thromboxane receptor antagonist, BMS 180,291, in human platelets. AB - Binding and function of BMS 180,291 ([(+)1S-(1 alpha,2 alpha,3 alpha,4 alpha)]-2 [[3-[4-[(n-pentylamino)carbonyl]-2-oxazolyl]-7- oxabicyclo[2.2.1] hept-2 yl]methyl]benzenepropanoic acid]) in human platelets was examined. Kinetic determination of [3H]BMS 180,291 binding produced ligand-receptor association and dissociation rates of 1.4 x 10(7) +/- 0.2 M-1 x min-1 (n = 5) and 0.04 +/- 0.005 min-1 (n = 5), respectively. The resultant Kd was 3.1 +/- 1.1 nM (n = 5). Saturation binding analysis in platelet membranes was consistent with a single class of [3H]BMS 180,291 binding sites with a Kd of 3.6 +/- 0.19 nM (n = 4) and a binding site maxima (Bmax) of 2099.1 +/- 70.3 fmol/mg of protein (n = 4). Specific [3H]BMS 180,291 binding was inhibited by thromboxane A2/endoperoxide receptor antagonists and agonists with a rank order of potency of: BMS 180,291 > or = SQ 29,548 = I-BOP race 15-(1 alpha,2 beta(5Z), 3 alpha(1E,3S),4 alpha) d7-[3 (3-hydroxy-4-(p-iodophenoxy)-1-butenyl)-7- oxabicyclo[2.2.1]hept-2-yl]5-heptenoic acid) > or = BM 13,505 > or = SQ 30,741 = U 44,609 > U 46,619 >> BM 13,177. Prostaglandin E2 and prostacyclin did not appreciably inhibit the specific binding of [3H]BMS 180,291. BMS 180,291 (10 nM-5 microM) shifted the I-BOP induced platelet shape change curve to the right in a parallel manner without reduction of the maximal response (KB = 13 +/- 3.5 nM; pA2 = 8 +/- 0.2; slope = 1.0 +/- 0.05), whereas 30 nM drug decreased the maximal I-BOP-induced platelet aggregation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450474 TI - A behavioral and pharmacokinetic study of the actions of phenylcyclohexyldiethylamine and its active metabolite, phenylcyclohexylethylamine. AB - Phenylcyclohexyldiethylamine (PCDE) is an analog of phencyclidine with low affinity for the N-methyl-d-aspartate receptor that is metabolized to an active monoethyl derivative, phenylcyclohexylethylamine (PCE). In a pharmacokinetic analysis of the ataxia response of rats to i.p. administered PCDE and PCE, ataxia intensity was determined together with plasma and cerebrospinal fluid concentrations of the drugs. The role of PCE as the active metabolite of PCDE was assessed quantitatively by correlating the response with both the plasma and cerebrospinal fluid drug levels. Increased PCE concentrations in the cerebrospinal fluid and plasma were associated with increased ataxia response when either PCDE or PCE was the administered drug. However, the concentration response curves did not superimpose and the curve after PCDE was shifted to the left of that after PCE, suggesting that PCDE was contributing an effect not accountable by PCE concentration. This apparent potentiation must involve an interaction at sites other than the N-methyl-daspartate receptor. In the analysis of the behavior responses, PCDE was found to induce a greater backpedalling response which has been attributed to interaction with dopamine or serotonin systems, suggesting that other transmitter systems may contribute to the overall ataxia response. PMID- 8450475 TI - Manipulation of endogenous adenosine in the rat prepiriform cortex modulates seizure susceptibility. AB - A1 adenosine receptors in the rat prepiriform cortex play an important role in the inhibition of bicuculline methiodide-induced convulsions. In the present study we evaluated manipulation of endogenous adenosine in this brain area as a strategy to effect seizure suppression. All compounds evaluated were unilaterally microinjected into the rat prepiriform cortex. Administration of exogenous adenosine afforded a dose-dependent protection (ED50 = 48.1 +/- 8.4 nmol) against bicuculline methiodide-induced seizures, and these anticonvulsant effects were significantly potentiated by treatment with an adenosine kinase inhibitor, 5' amino-5'-deoxyadenosine; by the adenosine transport blockers, dilazep or nitrobenzylthioinosine 5'-monophosphate; and by an adenosine deaminase inhibitor, 2'-deoxycoformycin. When administered alone, 5'-amino-5'-deoxyadenosine, 5' iodotubercidin and dilazep were found to be highly efficacious as anticonvulsants with respective ED50 values of 2.6 +/- 0.8, 4.0 +/- 2.7 and 5.6 +/- 1.5 nmol. In contrast, 2'-deoxycoformycin was both less potent and less efficacious. These results suggest that accumulation of endogenous adenosine may contribute to seizure suppression, and that adenosine kinase and adenosine transport may play a pivotal role in the regulation of extracellular levels of adenosine in the central nervous system. The adenosine antagonist, 8-(p-sulfophenyl)theophylline, increased markedly the severity of bicuculline methiodide-induced seizures. Moreover, reduction of extracellular adenosine formation by a focal injection of an ecto-5'-nucleotidase inhibitor, alpha, beta-methyleneadenosine diphosphate, produced generalized seizures (ED50 = 37.3 +/- 22.7 nmol). Together the proconvulsant effect of an adenosine receptor antagonist and the convulsant action of an ecto-5'-nucleotidase inhibitor further support the role of endogenous adenosine as a tonically active antiepileptogenic substance in the rat prepiriform cortex. PMID- 8450476 TI - A potent inhibitory effect of erythromycin and other macrolide antibiotics on the mono-N-dealkylation metabolism of disopyramide with human liver microsomes. AB - Clinical observation has suggested that erythromycin (EM) may cause an elevation in plasma disopyramide (DP) concentrations and thereby cause potentially fatal arrhythmias in certain patients. To determine whether EM would interfere with the in vivo pharmacokinetics of DP and whether other macrolides would share this action with EM, the effects of EM and other macrolide antibiotics on the in vitro DP metabolism to its major metabolite, mono-N-dealkyldisopyramide, were studied with human liver microsomes obtained from eight patients who underwent partial hepatectomy. The mono-N-dealkylation of DP proceeded with a biphasic enzyme kinetic profile, suggesting that at least two distinct enzyme sites or components are involved in the DP metabolism in humans. The high- and low-affinity sites gave the mean (+/- S.D.) Km of 5.7 +/- 2.8 and 724.7 +/- 427.4 microM, and Vmax of 2.90 +/- 1.17 and 18.20 +/- 8.84 nmol/hr/mg protein, respectively. Because the mean intrinsic clearance (i.e., Vmax/Km) for the high-affinity site (i.e., 0.79 +/- 0.69 ml/hr/mg protein) was about 30 times greater than that for the low affinity site (i.e., 0.03 +/- 0.01 ml/hr/mg protein), the high-affinity site was considered more important in the DP metabolism at its therapeutic concentrations (i.e., 2-5 micrograms/ml or 5-14 microM). EM inhibited the high-affinity site activity in a noncompetitive manner with the mean Ki of 19.5 +/- 1.3 microM (n = 4). An EM concentration associated with a 50% suppression of the DP metabolism at 30 microM (i.e., IC50) was 94 microM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450477 TI - Lack of evidence for the involvement of cytochrome P-450 or other hemoproteins in metabolic activation of glyceryl trinitrate in rabbit aorta. AB - The present study was conducted to test the hypothesis that glyceryl trinitrate (GTN) metabolic activation in blood vessels is mediated by cytochrome P-450 or some other hemoprotein. The effects of cytochrome P-450 inhibitor [2 dimethylaminoethyl-2,2-diphenyl-n-pentanoate (SKF-525A) and metyrapone] on the response of rabbit aortic rings to GTN was determined by recording cumulative GTN dose-response curves in the presence of either or both inhibitors. The cytochrome P-450 inhibitors did not interfere with the ability of GTN to relax rabbit aortic rings. Treatment of rabbit aortic strips (RAS) with carbon monoxide (CO) was undertaken to elucidate a potential role of ferrous hemoproteins in mediating GTN induced relaxation. CO did not significantly inhibit GTN-induced vasodilation of RAS. Biotransformation of GTN to glyceryl dinitrates by RAS exposed to CO for 5 min or nitric oxide (NO) for 10 min was determined by incubation of the tissues with 0.5 microM [3H]- or [14C]-GTN in the presence of CO or NO for 10 sec, 30 sec or 2 min. Neither CO nor NO exposure inhibited glyceryl-1,2- or -1,3-dinitrate formation by RAS after the 10-sec or 2-min incubation with RAS. For the 30-sec incubation, NO exposure did inhibit glyceryl dinitrate formation by RAS. This was deemed to be less important than the 10-sec data, the time just before the onset of relaxation. Therefore, emphasis is placed on lack of inhibition by NO at this earlier time point.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450478 TI - Behavioral effects of the 5-hydroxytryptamine3 receptor agonists 1 phenylbiguanide and m-chlorophenylbiguanide in rats. AB - We have investigated the behavioral effect of the 5-hydroxytryptamine3 (5-HT3) receptor agonists 1-phenylbiguanide (PBG) and m-chlorophenylbiguanide (mCPBG) in rats after i.p. and i.c.v. injection. It was hoped that this approach may provide an alternative means of studying the role of 5-HT3 receptors on animal behavior, for the majority of related studies have used antagonists at this subtype. Both PBG (3-60 mg/kg, i.p.) and mCPBG (1-30 mg/kg i.p.) produced abdominal constrictions, writhing and salivation in some, but not all, rats. The most marked behaviors were seen after mCPBG (30 mg/kg, i.p.), where paw shakes and chin rubbing was also recorded. Almost certainly as a consequence of these behaviors, PBG (3-30 mg/kg, i.p.) and mCPBG (0.3-10 mg/kg, i.p.) produced a conditioned place aversion. Pretreatment with the 5-HT3 antagonists ondansetron (0.01-0.1 mg/kg, s.c.), ICS205-930 and quaternized ICS205-930 (both 0.1 mg/kg, i.p.) blocked the PBG (30 mg/kg, i.p.)-induced place aversion. PBG (30 mg/kg, i.p.) and mCPBG (10 mg/kg, i.p.) also produced a conditioned taste aversion. The central administration of PBG (1-30 micrograms, i.c.v.) and mCPBG (0.1-10 micrograms, i.c.v.) enhanced locomotor- and gnawing-related behavior, although the effects with PBG seemed more consistent. These PBG (10 micrograms, i.c.v.) induced behaviors were completely blocked by haloperidol (0.01-0.1 mg/kg, s.c.). In contrast, ondansetron (0.0001-1 mg/kg, s.c.) and ICS205-930 (0.1 mg/kg, i.p.) produced only a mild and inconsistent attenuation of these responses. PBG (1-30 micrograms, i.c.v.) failed to produce any place conditioning (i.e., neither a preference nor aversion was found). It is concluded that activation of peripheral 5-HT3 receptors leads to aversive-type behaviors, which may be related to gastrointestinal discomfort or malaise. In contrast, central injection of PBG and mCPBG produced a range of dopamine-related behaviors; however, a 5-HT3 receptor involvement is unclear. Because both PBG and mCPBG have dopamine releasing properties, the use of 5-HT3 agonists lacking such effects and/or the use of more discrete microinjection studies are needed to more clearly elucidate the roles of 5-HT3 receptors in the central nervous system. PMID- 8450479 TI - Competitive inhibition of phospholipase A2 activity by the platelet-activating factor antagonist Ro 19-3704 and evidence for a novel suppressive effect on platelet activation. AB - The compound Ro 19-3704 [3-4(R)-2-(methoxycarbonyl) oxy-3-(octadecylcarbamoyl)oxy propoxy butylthiazolium iodide], initially described as an antagonist of platelet activating factor, is reported here to directly inhibit rabbit platelet phospholipase (PL) A2 activity, with an IC50 value of 4 to 7 microM. Classical Michaelis-Menten analysis showed that inhibition was reversible and competitive, inasmuch as apparent Km values increased in the presence of Ro 19-3704 (from 0.2 0.4 to 2 microM), whereas Vmax values remained constant (200 +/- 20 nmol/min/10(9) cells). Ro 19-3704 inhibited platelet aggregation, PLA2 release and thromboxane B2 formation induced by thrombin (0.25 U/ml), with IC50 values of 8, 15 and below 5 microM, respectively. Aggregation and PLA2 release by arachidonic acid (100 microM) were also inhibited, but thromboxane B2 formation was unaffected, indicating that Ro 19-3704 does not inhibit cyclooxygenase. Platelet activation by collagen (5 micrograms/ml), the thromboxane mimetic U46619 ([15(S)-hydroxy-11,9(epoxymethano)-prosta-5Z,13E-dienoic acid] 1 microM) and low concentrations of thrombin (0.05-0.1 U/ml) was also inhibited by Ro 19-3704. Inhibition of platelet activation was reversible, suggesting that its suppressive effect was not due to cytotoxicity. Finally, Ro 19-3704 did not stimulate cyclic AMP formation or inhibit phosphodiesterase activity. Ro 19-3704 is a competitive inhibitor of PLA2 activity, and is also endowed with a potent suppressive effect on platelet activation induced by different agonists. PMID- 8450481 TI - Inhalant abuse: assessment guidelines. AB - It is important that nurses have full access to information that would help them identify inhalant abuse. Nurses need to take the leadership in assessing clients, in educating health care professionals and the public, and in promoting legislation to prevent minors from obtaining inhalants. PMID- 8450480 TI - Induction of liver cytochrome P4502E1 by pyrazole and 4-methylpyrazole in neonatal rats. AB - Cytochrome P4502E1 (P4502E1) is not present in fetal rat liver; activation of the gene occurs within hours after birth. In adult rats, chemical inducers increase P4502E1 levels largely by a post-transcriptional type of mechanism. Experiments were carried out to evaluate how soon after birth chemicals such as pyrazole or 4 methylpyrazole (MP) can induce P4502E1 and whether the mechanism for induction at these early developmental stages, during active transcription, is different from that found in adults. No P4502E1 was found in fetal liver; in liver microsomes from saline control rats, there was a progressive increase in P4502E1 levels and oxidation of dimethylnitrosamine every 2 days after birth, with maximal levels 8 to 14 days after birth. Injecting pyrazole and MP on day 0 and day 1 after birth, resulted in 2- to 4-fold increases (compared to saline control values) in P4502E1 content and oxidation of dimethylnitrosamine in liver microsomes isolated from 2 day-old pups. This extent of increase by treatment with pyrazole or MP over saline control values was similar to that found when pups were treated for 2 days with the inducers on days 2, 4, 6, 8, 12 and 19 after birth. Northern blot analysis indicated a progressive increase in P4502E1 mRNA levels, reaching a maximum at about 8 days after birth for saline-treated pups. Pyrazole or MP did not increase P4502E1 mRNA levels over values for the saline controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450482 TI - Physical health promotion in psychiatric day treatment. AB - Physiological and self-care needs are often neglected in the treatment of chronic psychiatric patients. In an attempt to treat the whole person, a stress and health management program was implemented in the partial hospitalization program of a large, urban medical center, with the goal of improving client capabilities and self-esteem. The Psychiatric Day Treatment Center was a nurse-coordinated program held Monday through Friday from 9 to 4 in an office separate from the hospital. Most patients attended from 2 weeks to 6 months, at first on a daily basis, and then tapered off to a part-time schedule as they neared discharge. The population was varied with regard to age, educational, and socioeconomic background. Clients ranged in age from 16 to 85; some participants were professionals, while others had not completed high school. When they left the program, some clients were able to manage part-time jobs, while others opted for volunteer work or for longer term day treatment. All clients had been previously hospitalized for treatment of psychiatric illness. Some clients attended the program to avoid another hospitalization, as it offered more intensive treatment and medication management than the weekly outpatient treatment did. Some clients used the program to ease the transition between hospital and community. Clients who needed more stimulation and interaction than they were receiving also participated. PMID- 8450483 TI - Living with mental illness: the family as caregiver. AB - 1. Families of persons with severe mental illness are often anguished because of stressors and are unprepared to be caregivers. Their needs must be addressed by mental health professionals. 2. Family members may experience grief, guilt, anger, powerlessness, and fear. 3. Education and peer groups may be most helpful to family members in dealing with their distress and becoming better prepared caregivers. PMID- 8450484 TI - Living with mental illness: professional/family collaboration. AB - What started as a pilot project in the spring of 1990 has matured into a successful ongoing enterprise between professionals and families that continues to meet the needs of families experiencing the impact of mental illness. According to self-administered evaluations completed by those in attendance, and a subjective review by the planning committee, the program was an immediate success. It attained its overall education and mutual support objectives, and fostered successful collaboration between professionals and families. One hundred percent of family participants indicated that they would recommend the workshop to others in similar situations. In managing mental illness through collaborative partnerships, the family must be an integral part of each phase of project development. Family members are the "thermometer," measuring how closely the project is mirroring their needs. Since its inception, 370 people have participated in this dynamic project. This program demonstrates that through understanding, respect, and positive regard, families, friends, and professionals can work collaboratively to enhance the quality of life for all who are victimized by mental illness. PMID- 8450485 TI - A comparison: an open psychiatric unit in the US and Germany. AB - 1. Psychiatry reform occurred not only in the US but in Europe as well. As a result, psychiatric units in general hospitals were established both here and abroad. 2. Principles of psychiatric nursing also changed. In the US and Germany, guidelines emphasized the goal of a patient's self-sufficiency rather than dependency on staff and institutions. 3. Psychiatric staff nurses in Germany receive additional and continued education, whereas academic advancement and specialization prepares the nurse specialist in the US. 4. The daily routine on a German psychiatric unit includes preadmission interviews, more liberal passes and outings for patients, overlapping shifts, and an emphasis on "supervision." PMID- 8450486 TI - A nurse-led educational program in psychiatric settings: developing a curriculum. AB - 1. Psychoeducation provides patients with the tools necessary for social reintegration through education; the practice of skills has the potential to empower mentally ill clients. 2. Psychoeducation programs should include a needs assessment and input from the staff and patients as well as consulting literature. Staff involvement elicits creative ideas and can help implement and maintain a good program. 3. Psychoeducation programs can provide opportunities for education, appropriate role modeling of skills, and ongoing assessment of client's progress, as well as generate questions for research regarding the efficacy of different modalities. 4. Psychoeducation classes should consider time factors, client mix, and should have an evaluative component. They should also build on knowledge from each preceding class and be interesting, relevant, and fun. PMID- 8450487 TI - Genetic link between depression and substance abuse found. PMID- 8450488 TI - Moving into the mainstream. PMID- 8450489 TI - Research and society: a relationship with two faces. AB - Biomedical research has been and will continue to be essential for improving the quality of life but is also the origin of many of society's adverse reactions and problems. These are related to such issues as unfulfilled hopes, ethical considerations, potential misuse and financial constraints. They particularly endanger basic research and favour non-scientific-based practices in medicine. Future challenges for research include continuous improvement of its quality, conscientiousness, responsibility, communication with society and critical openness for unconventional approaches. PMID- 8450490 TI - A computer program for motion analysis of single cardiac myocytes. AB - Single adult cardiac ventricular cells were prepared by collagenase perfusion of a rat heart. They were stimulated electrically in a perfusion chamber and their length changes were followed under a microscope. The motion was followed via a video camera and by a TV-line counting device and was recorded on-line by a personal computer. The program RECORD was used to calculate peak amplitude, base line drift and peak width at different peak heights allowing the determination of a number of variables of the cellular motion. The method was applied to drugs affecting the amplitude of contractions and the speed of relaxation. Results of beta-adrenergic stimulation, muscarinic inhibition and of the Ca(2+)-ATPase inhibitor cyclopiazonic acid (CPA) are shown. Besides its stimulatory effect on length, the beta-adrenergic agonist isoprenaline concentration-dependently shortened relaxation time. Carbachol reversed the increase in cellular shortening caused by isoprenaline in a concentration-dependent manner without fully reversing the shortened relaxation. CPA prolonged the return to diastole, presumably due to its inhibition of Ca(2+)-reuptake into the sarcoplasmatic reticulum. PMID- 8450491 TI - A method for radioligand binding assays using a robotic workstation. AB - Radioligand binding assays provide a powerful tool for screening drug candidates at many receptors. We present a method utilizing a robotic workstation, the Biomek 1000, which automates the tedious and repetitive tasks of these assays. First, the robot handles the serial dilution of up to 8 drugs with 11 concentrations per drug. The sequential addition of diluting buffer, non radioactively labeled ligand, radioactive ligand, and finally the tissue homogenate or membrane preparation, is fully automated. A novel rack design allows the use of tubes with a maximum capacity of 2 ml, providing a total assay volume of 1 ml. Final filtration on a Brandel cell harvester outfitted with a uniquely designed head allows for processing of 48 samples simultaneously from the rack holder. We have employed this method for the determination of equilibrium dissociation constants (Kds) for drugs at the 5 human muscarinic acetylcholine receptor subtypes expressed in cultured cells, as well as histamine H1, dopamine D2, serotonin 5HT1A, alpha 1- and alpha 2-adrenergic receptors in human brain tissue homogenates. Our results compare favorably with manual methods reported for these receptors, and exhibit a very high degree of reproducibility and throughput, with a minimum of operator input. PMID- 8450492 TI - Cyclopeptide analogs for characterization of the neuropeptide Y Y2-receptor. AB - A discontinuous 17-amino acid peptide analog of neuropeptide Y (NPY), NPY 1-4-Ahx 25-36 containing 6-aminohexanoic acid instead of the residues 5 to 24, was found to bind preferentially to Y2 subtypes of NPY receptors. In order to further characterize the binding site, three different types of cyclic analogs were synthesized. Firstly lactamisation between residues 2 and 30 led to the most selective Y2-agonist, secondly lactamisation between the N-terminus and residue 31 reduced binding significantly. Thirdly, any cyclization including the C terminus led to an inactive compound. Circular dichroism revealed different conformations for the three analogs with reduced alpha-helical content in comparison to the linear ana-log. The different conformation of the peptides has been confirmed by molecular dynamics simulations. A model for peptide-receptor interaction is suggested. PMID- 8450494 TI - Vasopressin receptors in adrenal cortex of sheep: does autoradiography indicate an irreversible binding of the ligand? AB - Tritiated arginine vasopressin ([3H]-AVP) labelled specific loci of murine renal medulla and ovine adrenal cortex in thin sections of an autoradiographic experiment. The label was fully displaced by 2 x 10(-6) M cold ligand in the case of renal, but not of adrenal sections. 10 and 100 microM AVP, however, partially displaced the radioactivity also from labelled adrenal sections. At room temperature, the half maximal blackening of the film occurred at a concentration of 26 +/- 0.9 microM. In binding experiments employing AVP and adrenocortical cell membranes, the model assuming two saturable binding sites yielded a significantly better fit than the one-site model. The equilibrium dissociation constants of ice-cold membrane preparations were 8.67 nmol/l for the high affinity site and 3.16 mumol/l for the low affinity binding site. It is concluded that the low affinity binding is governed by laws of chemical equilibrium, rather than by surface adsorption or similar "nonspecific" phenomena. When such low affinity sites are present in a tissue, higher concentrations of cold ligand ought to be used before a nondisplaceable binding is ascribed as "non-specific" or "irreversible". PMID- 8450493 TI - Receptor binding and biological activity of IL-1 alpha, IL-1 beta, IL-1 beta analogues and an IL-1 antagonist in A375 human melanoma cells. AB - A receptor binding assay for IL-1 peptides on human melanoma cells of the A 375 cell line is reported. Strains differing in their sensitivity to the cytotoxic effects of IL-1 beta were compared. In both strains, binding equilibrium at temperatures between 0 degrees and 37 degrees C was reached after 4 to 8 hours. At 37 degrees C, most of the bound ligand was rapidly internalized leaving a constant level of surface receptors. Scatchard analysis at 0 degrees C revealed a single class of high affinity receptors with a similar KD in both IL-1 resistant (0.18 +/- 0.07 nM) and sensitive strains (0.14 +/- 0.06 nM) but a 10-fold difference in the number of binding sites. Whereas > 1000 binding sites per cell were regularly observed in all resistant strains, only 100-200 sites could be detected on the IL-1 sensitive cells. In displacement assays, IL-1 beta was found to be slightly more potent than IL-1 alpha in both strains. In an attempt to further characterize the IL-1 binding site in these cells, the binding characteristics and biological activity of 20 point mutations of IL-1 beta were examined. EC50 values similar to those of the wild type peptide were found in all these analogues with the exception R11S and E128K: their EC50 was increased by a factor of 10 but the biological activity was reduced 1000-fold as compared to IL 1 beta. The relative potency of an IL-1 receptor antagonist was similar to that of IL-1 beta in the displacement binding assay but a 100-fold higher concentration was required to completely block the cytotoxic effects of IL-1 beta. These results show that A375 human melanoma cells are useful for screening the binding and biological properties of analogues of the IL-1 family of peptides. PMID- 8450495 TI - Tissue plasminogen activator enhancing activity of vasopressin analogues in monkeys: structure-activity study. AB - Marmocets were used in a structure activity study of the ability of vasopressin analogues to activate plasminogen activator (tPA). In evaluation of dDAVP analogues with L-alanine migrating from position 2 to 9 we found [L-Ala4]dDAVP and [L-Ala5]dDAVP to be potent activators of tPA. Double substitutions in dDAVP showed that combinations of a modification in position 4 valine with a change at position 2 (2-O-methyltyrosine) generated tPA releasing activity. On the other hand enlargement of the substituent at position 2 (2-O-ethyltyrosine) completely eliminated the activity of [L-Val4]dDAVP. The tPA activity is dependent on the position of a positively charged group at the amino acid in position 8 of the peptide chain. A shift of the guanido group further away from the backbone (D arginine to D-homoarginine) resulted in a loss of tPA activating properties. PMID- 8450496 TI - Chronic antagonist treatment does not alter the mode of interaction of dopamine with rat striatal dopamine receptors. AB - Chronic treatment with the D1 and D2 dopamine receptor antagonists SCH 23390 (0.5 mg/kg) and haloperidol decanoate (25 mg/kg) caused an up-regulation in D1 and D2 receptor densities, respectively, with no change in KD. Dopamine (20 microM) interacted with both receptor subtypes in a mixed competitive/non-competitive manner, causing a reduction in ligand binding affinity and an apparent decrease in receptor density. In the presence of dopamine, both vehicle-treated and SCH 23390-treated striatal preparations showed a significant loss in affinity for 3H SCH 23390 binding to D1 receptors and a decrease in D1 receptor density of approximately 26%. Similarly, dopamine caused a substantial loss in 3H-spiperone binding affinity to D2 receptors and a 46% decrease in Bmax in both vehicle treated and haloperidol-treated membranes. Thus, receptor up-regulation does not appear to alter the mode of interaction of dopamine with rat striatal dopamine receptors. PMID- 8450497 TI - Selective down-regulation of the agonist-dependent high affinity state of rat cortical 5-HT2 receptors following chronic treatment with amperozide. AB - Amperozide, a putative antipsychotic drug, is a selective serotonin 5-HT2 receptor antagonist with moderate affinity for the rat brain dopamine D2 receptor. The aim of the present study was to investigate the regulation of 3H ketanserin binding of the rat cerebral cortex 5-HT2 receptor following chronic amperozide treatment. Amperozide (5 mg/kg/day p.o. for three weeks) significantly reduced the number of 5-HT2 receptors in rat cerebral cortex (172.9 +/- 8.3 vs 128.4 +/- 4.8 fmol/mg protein; p < 0.001, n = 5-6). There was no change of Kd of 3H-ketanserin. The agonist serotonin (5-HT) recognized two sites of 3H-ketanserin binding in membranes from both saline- and amperozide-treated rats as analysed by non-linear regression using LIGAND. The concentration of high affinity sites was reduced by 51% (53.1 +/- 2.9 vs 25.7 +/- 3.7 fmol/mg protein; p < 0.01, n = 3) while the amount of the low affinity sites remained unchanged. Serotonin displacement of 3H-ketanserin binding was sensitive to regulation by GTP. The present data indicated that GTP regulation was partially lost following chronic amperozide treatment. Displacement of the antagonists methysergide and amperozide were not affected by GTP. In conclusion, the down-regulation of the 5-HT2 receptors appears mainly due to a decrease of the serotonin-recognized high affinity state, and the loss of GTP sensitivity may indicate a decreased ability to form the high affinity state of the receptor. Such a molecular regulation might underlie an altered 5-HT responsiveness and thus be of therapeutic value. PMID- 8450498 TI - A novel agonist binding site on nicotinic acetylcholine receptors. AB - This report provides evidence that physostigmine (Phy) and benzoquinonium (BZQ) are able to activate nicotinic acetylcholine receptors (nAChRs) through binding site(s) distinct from those of the natural transmitter, ACh. Such findings are in agreement with a second pathway of activation of nAChRs. Receptor activation may be modulated through the novel site, and, consequently, physiological processes involving nicotinic synapses could be controlled. Using patch clamp techniques, single channel currents activated by ACh and anatoxin were recorded from frog interosseal muscle fibers under cell-attached condition and outside-out patches excised from cultured rat hippocampal neurons. Whole cell nicotinic currents were also studied in the cultured neurons. In most of the neurons, nicotinic responses were blocked by the nicotinic antagonists methyllycaconitine (MLA) and alpha bungarotoxin (alpha-BGT). Evaluation of the effects of Phy and BZQ on the muscle and on the alpha-BGT- and MLA-sensitive neuronal nAChRs demonstrated that both compounds were open channel blockers at these receptors. Furthermore, at low micromolar concentrations, Phy and BZQ activated the nAChRs of all preparations tested, such an effect being unexpectedly resistant to alpha-BGT or MLA. Thus, the nAChRs could be activated via two distinct binding sites: one for ACh and the other for Phy and BZQ. These findings and previous biochemical results led us to suggest that a putative endogenous ligand could bind to the new site and thereby regulate the activation of nAChRs in nicotinic synapses. PMID- 8450499 TI - Muscarinic receptor regulation and 2nd messenger responses in rat neocortex cultures. AB - Primary cultures of dissociated cerebral cortex cells were used to characterize the muscarinic acetylcholinergic receptors (mAChR) present and to study receptor down-regulation and receptor mediated 2nd messenger responses induced by muscarinic agonists. Binding of the hydrophilic antagonist [3H]N-methyl scopolamine ([3H]NMS) to the cultured cells was saturated after one hour at 4 degrees C with a Kd of 93 pM and a Bmax of 958 fmol/mg protein. Competition binding studies with several antagonists and agonists indicated that the mAChR present in the culture were of a mixed M1/M3 subtype. The number of muscarinic receptors at the cell surface decreased by 60% after one hour pre-incubation of the cultures with 10 microM carbachol or oxotremorine. After down-regulation with carbachol affinity for pirenzepine was decreased, while low affinity sites for 4 DAMP were lost, indicating that especially M1 subtypes are sensitive to this type of regulation. Carbachol and oxotremorine-M induced a 2-3 fold increase in phosphatidyl inositide (PI) turnover, which was blocked with high affinity by both pirenzepine and 4-DAMP. Down-regulation of the mAChR and stimulation of PI turnover by agonists with different potency and intrinsic activity appeared highly correlated. These data suggest that activation of the PI second-messenger system is involved in the desensitization and down-regulation of the muscarinic acetylcholine receptor. PMID- 8450500 TI - Anti-peptide specific antibodies for the characterization of different alpha subunits of alpha-bungarotoxin binding acetylcholine receptors present in chick optic lobe. AB - Chick optic lobe express alpha-Bungarotoxin receptors. We have recently purified these receptors which, when reconstituted in a lipid bilayer, behave as functional acetylcholine gated channels. In order to characterize this purified preparation, we raised polyclonal antibodies against peptides obtained from the putative cytoplasmic domain between the hydrophobic sequence M3 and M4 of two previously cloned alpha-Bungarotoxin receptor subunits, alpha 7 and alpha 8. Both antibodies recognized the receptors present in the membrane extract and in the purified preparation, although the amount of the alpha-Bungarotoxin receptors precipitated by the two antibodies was quantitatively different. In Western blots of both purified and membrane-bound receptors, these antibodies specifically reacted with an M(r) 57000-55000 band. A study was also undertaken to quantify the receptors containing these subunits in different chick brain areas; it was found that the number of these subunits, as well as their ratio, was similar in all the tested areas. Furthermore, the alpha-Bungarotoxin receptors were present in at least two subtypes, one containing only the alpha 7 subunit and the other both alpha 7 and alpha 8 subunits. PMID- 8450501 TI - Structure functional expression and spatial distribution of a cloned cDNA encoding a rat 5-HT1D-like receptor. AB - Using polymerase chain reaction (PCR) a complementary DNA (cDNA) encoding a 5 hydroxytryptamine (5-HT) receptor was isolated from rat forebrain. The amplified cDNA specifies an open reading frame of 374 amino acids comprising seven putative transmembrane regions. Expression of the cloned cDNA in human embryonic kidney cells (HEK 293) was used to establish the pharmacological profile of the encoded receptor polypeptide. Membranes containing the cloned receptor showed high affinity binding of [3H]-5-HT. Competition binding experiments with a variety of serotonin receptor ligands displayed a rank order of affinities corresponding to a 5-HT1D subtype: 5-CT > 5-HT = metergoline > CGS 12066 > methysergide > sumatriptan > mianserin = (-)alpha-Me-5-HT = yohimbine > 8-OH-DPAT > or = rauwolscine > spiperone > DOI > propranolol > or = 2-Me-5-HT > or = ICS 205930. Ketanserin and ritanserin displaced [3H]-5-HT-binding in a biphasic manner. In situ hybridization revealed highest expression of the corresponding mRNA in the pyramidal layer of the olfactory tubercle and the nucleus caudatus and accumbens. PMID- 8450502 TI - The Xenopus oocyte as an ectopic expression system for the selection of protein isoform-specific antibodies. AB - A panel of Xenopus oocytes, each injected with cRNA coding for one specific isoform of the rat brain RCK family of voltage gated potassium channel proteins, was employed to screen for isoform-specific monoclonal antibodies. Several days after injection, cryosections of embedded oocytes were produced and were employed in immunohistochemical analysis of antibody binding. Of the advantageous properties of the assay, it employs the native antigen, it can be applied to homooligomeric and heterooligomeric proteins, and cryosections of the same batch can be stored frozen for later tests. The method may be advantageous also for the selection of isoform-specific antibodies of other protein families. PMID- 8450503 TI - Towards an identification of odorant receptors. AB - The molecular nature and diversity of receptive sites for odorous molecules is a central unanswered issue in olfaction. Based on the enormous resolving power of the olfactory system, which enables the stereospecific discrimination of numerous compounds at low concentrations specific receptor proteins have been proposed. Due to the central role of G-proteins in olfactory signalling it has been predicted that odorant receptors might be members of the superfamily of receptor proteins with seven transmembrane domains. Upon application of degenerated oligonucleotides and the PCR-technology a number of putative odorant receptors have been cloned and sequenced. In situ hybridisation studies using receptor specific probes have been performed and olfactory neurons specifically expressing a particular receptor subtype are topologically identified in the nasal epithelium of rats. Clones of interest are now being expressed in heterologous systems in order to demonstrate functional activity of these putative receptor proteins and to match defined odorants to identified receptors. PMID- 8450504 TI - Dopaminergic activity measured in D1- and D2-transfected fibroblasts by silicon microphysiometry. AB - The dopaminergic system implicated in human disorders such as Parkinson's disease, schizophrenia and prolactinomas, exerts its effects through several dopamine receptors. The diversity of the dopaminergic system has been revealed by the application of molecular biology techniques to this system, which allowed the identification of five different types of dopamine receptors to date. Even though the structure of these receptors has now been identified, their physiological roles are still under investigation. The coupling of the D1 and D2 dopamine receptor to second messengers has been investigated using cell lines transfected with the cDNAs of these receptors. However, until recently, there was no technique allowing non-invasive real-time measurement of the metabolic activity of cells after agonist stimulation. We present here real-time measurement of events induced by dopaminergic agents on either the D1 or the D2 dopamine receptors using a novel technique employing a silicon-based microphysiometer. PMID- 8450505 TI - Molecular cloning, stable expression and desensitization of the human dopamine D1b/D5 receptor. AB - The sub-family of dopamine D1-like receptors is now known to be comprised of at least two members: the originally cloned D1 receptor (herein referred to as the D1a receptor) and a related receptor referred to as the D1b, D1 beta or D5 dopamine receptor (herein referred to as the D1b/D5 receptor). Here, we characterize the D1b/D5 receptor expressed transiently in COS-7 cells and permanently in Ltk- cells. Transiently expressed human D1b/D5 receptors bind the D1 specific ligand [125I]SCH 23982 saturably and with high affinity (KD = 500 pM). Competition for [125I]SCH 23982 binding to rat D1b/D5 and human D1a and D1b/D5 receptors supports the contention that the two D1b/D5 receptors are species homologues. Furthermore, in COS-7 cells, as previously observed, dopamine competes for the binding of [125I]SCH 23982 to human D1b/D5 receptors with a higher affinity than that seen at the human D1a receptor. These results are similar to those seen in Ltk- cells permanently transfected with the human D1b/D5 receptor. In these cells, dopamine competition for [125I]SCH 23982 binding is complex, sensitive to guanine nucleotides and of a higher affinity than that observed for dopamine binding to the human D1a receptor expressed in these same cells. In both D1a and D1b/D5 expressing Ltk- cells, dopamine stimulates adenylyl cyclase with an EC50 of approximately 200 nM. Furthermore, preincubation of Ltk- cells expressing the D1a and D1b/D5 receptors with dopamine results in desensitization of the response of adenylyl cyclase to subsequent agonist stimulation. PMID- 8450506 TI - Comparative analysis of beta-adrenergic receptor kinase and beta-arrestin mRNA expression in human cells. AB - Receptor phosphorylation is a key step in the process of rapid desensitization. beta-Adrenergic receptor kinase is a specific receptor kinase that is known to phosphorylate and induce desensitization of several G-coupled synaptic receptors only when they are occupied by their agonists. We recently cloned human beta ARK cDNA and reported high levels of beta ARK expression in human peripheral blood leukocytes, also providing the first evidence for its possible functional role in these cells. Complete homologous receptor desensitization by beta ARK requires an additional cytosolic factor, called beta-arrestin. In the present study, we have cloned a 212 bp fragment of the human beta-arrestin cDNA to perform a comparative analysis of beta ARK and beta-arrestin mRNA expression in various human cell types. We found that also beta-arrestin mRNA is abundant in non-innervated tissues and cells. The fact that the entire machinery for G-coupled receptor desensitization is highly expressed in these cells further supports the idea that beta ARK may regulate nonsynaptic as well as synaptic receptors. PMID- 8450507 TI - Targeting of the Gi2 alpha gene in ES cells with replacement and insertion vectors. AB - Five replacement vectors (RV) and one insertion vector (IV) were constructed in which ca. 10 kb of genomic Gi2 alpha sequence, flanked on one (IV) or both (RV) sides by a thymidine kinase (TK) marker, were disrupted by a Neo marker inserted into the NcoI site of exon 3. G418RFIAUR clones corresponding to ca. 4 x 10(8) ES cells electroporated with replacement vectors were analyzed and revealed no targeting event. The insertion vector, however, was integrated by a single reciprocal recombination resulting in a duplication of homology (Hit step; G418RFIAUS), which was lost--together with the plasmid and the TK sequences--by intrachromosomal recombination (Run step; G418RFIAUR). Thus, the Hit and Run strategy can be used with a selectable marker disrupting the targeted gene, giving rise to the same targeted product that would have been expected to arise from a double crossover with a replacement vector. PMID- 8450508 TI - Expression of a rat PDGF receptor beta ectodomain generates a low affinity ligand antagonist. AB - Platelet-derived growth factor (PDGF) controls migration and proliferation of mesenchymal cells and is thought to be involved in the pathophysiology of different diseases such as arteriosclerosis and tumorigenesis. In order to investigate the role of PDGF in rat models for such diseases, sufficient amounts of PDGF antagonists are needed. For this purpose we expressed the extracellular domain (ectodomain) of the rat PDGF receptor beta (PDGFR beta) in insect cells using a baculovirus vector. A hydrophilic octapeptide was added onto the N terminus of the receptor ectodomain to follow its expression with specific anti FLAG antibodies. The FLAG tag was also utilized to design a rapid two-step purification protocol. Purified FLAG-tagged rat PDGFR beta ectodomain had an affinity to PDGF-BB identical to the untagged ectodomain as determined by Scatchard analysis. FLAG-tagged PDGFR beta ectodomain in solution, however, did not compete for PDGF-BB binding to full length cellular receptors at concentrations expected for an high affinity antagonist. PMID- 8450509 TI - Specific CSF-1 binding on murine placental trophoblasts and macrophages serves as a link to placental growth. AB - Previous studies have shown that the colony-stimulating factor-1 (CSF-1), stimulates the in vitro proliferation of a fetally-derived adherent, phagocytic and non-specific esterase positive placental cell population which stains positively for cytokeratin and Mac-1. Binding experiments were designed to test whether this is a direct effect of the factor on these cells. Binding/elution as well as autoradiography experiments, show that adherent placental cells specifically bind CSF-1. Based on the expression of the endothelial markers cytokeratin and vimentin three subpopulations of cells were isolated from the murine placenta: labyrinthine-derived trophoblasts (cytokeratin positive, vimentin negative), spongiotrophoblast-derived trophoblasts (cytokeratin positive, vimentin negative) and placental macrophages (cytokeratin negative, vimentin positive). 3H-Thymidine incorporation assays as well as binding experiments, showed that these cells simultaneously respond to and bind the macrophage-specific factor CSF-1. Furthermore, the results indicate that isolated trophoblasts have a low rate of growth and they are very sensitive to mitogenic stimulation, whereas placental macrophages alone have a high rate of growth and therefore are less sensitive to the mitogenic stimulus. These findings are in favour of the existence of an important cytokine regulatory network in the murine placenta, where two major cell populations may collaborate possibly via soluble factors to stimulate placental growth and thus fetal development. PMID- 8450510 TI - Evidence for shared receptor proteins for human interleukin-3 and granulocyte macrophage colony-stimulating factor in the human M-07 cell line. AB - The biologic response of the human leukemia cell line M-07 to granulocyte macrophage colony stimulating factor (GM-CSF), interleukin 3 (IL-3) and interleukin 4 (IL-4) is mediated by a low number of high affinity receptors. Cross-competition studies revealed that IL-3 and GM-CSF partially inhibited the specific binding of the heterologous radiolabeled ligand, whereas IL-4 binding was not affected by these cytokines. The molecular mechanism of cross-competition was investigated by chemical crosslinking and immunoprecipitation. Trimolecular receptor complexes consisting of a major 73kDa and two minor 120 and 128kDa membrane proteins for IL-3, and a major 84kDa and two minor 120 and 130 kDa proteins for GM-CSF were found on M-07 cells. The 73 and 84kDa proteins represent distinct and non-linked membrane proteins and are identical with the cloned, low affinity IL-3 and GM-CSF receptor proteins (Gearing et al, 1989, Hayashida et al, 1990). The higher molecular weight proteins share common binding sites as evidenced by immunoprecipitation of double-crosslinked membranes. The 120/128kDa proteins are most likely identical with the recently cloned and shared beta subunit of the IL-3 and GM-CSF receptor (Kitamura et al, 1991) containing a single or two IL-3 and/or GM-CSF molecules. PMID- 8450511 TI - Mechanotransduction in stretch-induced hypertrophy of cardiac myocytes. AB - Mechanical loading of cardiac muscles causes rapid activation of a number of immediate-early (IE) genes and hypertrophy. However, little is known as to how muscle cells sense mechanical load and regulate gene expression. We examined roles of several putative mechanotransducers in stretch-induced hypertrophy of cardiac myocytes grown on a deformable silicone sheet. Using the patch-clamp technique, we found a single class of stretch-activated cation channels which was completely and reversibly blocked by gadolinium. The inhibition of this channel by gadolinium did not affect either stretch-induced expression of the IE genes or hypertrophy. Neither disruption of microtubules with colchicine nor that of actin microfilaments by cytochalasin D prevented the stretch-induced IE gene expression. Arresting contractile activity by tetrodotoxin did not affect the stretch-induced IE gene expression or hypertrophy. These results suggest that stretch-activated cation channels, microtubules, microfilaments, and contractile activity are not the mechanotransducers. Preliminary results suggest that cell stretch may cause a release of a growth factor(s), which in turn initiates a cascade of hypertrophic response of cardiac myocytes. PMID- 8450512 TI - Rhodopsin phosphorylation by transiently expressed human beta ARK1: a new method for drug development. AB - Receptor phosphorylation is a key step in the process of rapid desensitization of the beta-adrenergic and other related G-coupled receptors. A specific kinase (called beta-adrenergic receptor kinase, beta ARK) has been identified, which phosphorylates the agonist-occupied form of these receptors. We have cloned the cDNA for human beta ARK1. The full-length cDNA was inserted in an expression vector (pBJI neo) and used for the transfection of eukaryotic cells (COS7). The kinase activity of the cytosolic fraction of COS7 cells was assayed 72 hours after beta ARK1 transfection. A 40-70 fold increase in cytosolic beta ARK1 activity was observed. To validate this approach we demonstrated a different degree of kinase inhibition by various types of heparin. Our system, based on transient gene expression and in vitro phosphorylation of rhodopsin, represents a new method to screen for pharmacological agents acting on this kinase. PMID- 8450513 TI - Lack of effect of calcium carbonate supplementation on 24h blood pressure, angiotensin II reactivity and PTH(1-84) in essential hypertension. PMID- 8450514 TI - Antinuclear antibodies with enalapril. PMID- 8450515 TI - Low blood pressure levels and signs of myocardial ischaemia: importance of left ventricular hypertrophy. AB - To clarify a possible relationship between the level of BP and signs of myocardial ischaemia, two groups of treated hypertensive patients with (n = 12) and without (n = 18) increased left ventricular mass defined by echocardiography were investigated with 24h ambulatory BP and ECG monitoring. It was found that hypertensive patients with increased left ventricular mass had the following. (1) Higher systolic BP, heart rate (HR) and SBP x HR product during the night indicating a higher ventricular work load than hypertensives without increased LVM in this period. (2) This increased left ventricular work load during the night was concomitant with a lower DBP consistent with a lower perfusion pressure of the left ventricular myocardium. (3) Significantly depressed ST segment levels throughout the 24 hours with a significant positive correlation between BP and the level of the ST segment indicating increased ischaemic metabolic changes within the myocardium the lower the BP. (4) A higher ratio between the systolic SBP x HR product and DBP during sleep than in hypertensives without increased left ventricular mass, further corroborating that low DBP during the night might cause ischaemia through an imbalance between left ventricular work load and coronary perfusion pressure. We conclude that low BPs in hypertensive patients with increased left ventricular mass seem to induce ischaemia of the left ventricle. These findings provide a possible mechanism for the increased risk of ischaemic heart disease in hypertensive patients with low achieved BP. PMID- 8450516 TI - Lack of blood pressure increase with age in long-term hospitalised patients with the sequelae of acute carbon monoxide poisoning. AB - We investigated retrospectively age-related changes in BP and body composition in 44 men who had been hospitalised for up to 26 yrs as a result of carbon monoxide poisoning. The average age of the patients was 42.5 +/- 9.1 (SD) yrs on the first admission. The average period of hospitalisation was 19.5 +/- 5.9 yrs. The patients received mild salt restriction and daily exercise in the hospital. During the study period, nine patients developed hypertension and received antihypertensive treatment. The prevalence of hypertension in our study population was 205 per 1,000 and the incidence of hypertension (DBP > 95 mmHg) was 9.1 per 100 person years. Both prevalence and incidence appear to be lower than those in the general population. In the other 35 patients BP significantly decreased from 127.5 +/- 10.0 mmHg (SBP)/79.8 +/- 8.1 mmHg (DBP) at the time of the first examination to 120.8 +/- 16.3 mmHg/71.9 +/- 10.3 mmHg on the last examination. Body mass index did not change significantly during the study period. Hypertensive cardiovascular death was not observed throughout the study period. In conclusion, controlled diet, salt intake, physical exercise and isolation from the social stimuli achieved by a long-term hospitalisation may prevent increased BP and cardiovascular death. PMID- 8450517 TI - Effects of fish oil, nifedipine and their combination on blood pressure and lipids in primary hypertension. AB - In a double-blind, crossover, placebo-controlled study the effects of four weeks' treatment with 4.55 g/day of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on BP and serum lipids were assessed in 18 males with hypertension (WHO stage I-II). At the end of the double-blind phase, eight patients on placebo (olive oil) and ten patients on fish oil treatment were given nifedipine 20 mg twice daily added to their regimens for four weeks. Four weeks' fish oil treatment slightly reduced BP values; however, compared with placebo no changes were found. VLDL-cholesterol and triglycerides were significantly reduced by 24%, whereas total and LDL-cholesterol remained unchanged. Placebo did not change BP and lipid values. When nifedipine was added to fish oil/placebo, BP in the two groups was reduced to almost the same extent. When nifedipine was added to fish oil, total cholesterol was significantly reduced by 12% in comparison with baseline value and LDL-cholesterol was reduced by 15%, albeit insignificantly. Placebo plus nifedipine was lipid neutral. A significant correlation was found between the nifedipine-induced changes in supine mean arterial pressure and total, LDL- and VLDL-cholesterol, respectively, in those patients with and without fish oil treatment. In conclusion, the combined administration of fish oil and nifedipine possesses favourable antihypertensive and metabolic properties in hypertensive males with elevated lipid levels. PMID- 8450518 TI - Left ventricular cardiac structure and diastolic function in isolated systolic hypertension in the elderly. AB - We examined the left ventricular cardiac structure and the diastolic function in patients with isolated systolic hypertension (ISH; SBP > or = 160 mmHg and DBP < 90 mmHg) in the elderly. We studied 17 patients with ISH, 24 age-matched patients with essential hypertension (EHT; DBP > or = 90 mmHg) and 17 normotensive controls (NT; SBP < 140 mmHg and DBP < 90 mmHg). EHT were divided into two groups based on the mean wall thickness (MWT) of the left ventricle. Group 1 patients (EHT-I, n = 12) had a MWT < 10 mm and group 2 patients (EHT-II, n = 12) had a MWT > or = 10 mm. We measured left ventricular end-diastolic dimension (LVDd), end systolic dimensions (LVDs), left ventricular mass index (LVMi) and left ventricular isovolumic relaxation time (IRT) to assess the left ventricular cardiac structure and the diastolic function by M-mode echocardiography. LVDd was significantly smaller in ISH than in NT, EHT-I and EHT-II (P < 0.01). Relative wall thickness was greatest in ISH because of both the decreased chamber size and the increased left ventricular wall thickness. LVMi in ISH was similar to that in EHT-I, but IRT in ISH was significantly longer than that in EHT-I (P < 0.05). These results suggest that ISH in the elderly shows a left ventricular concentric hypertrophy and a severely impaired diastolic function. PMID- 8450519 TI - Platelet intracellular pH and glucose metabolism in hypertensive patients. AB - Intracellular platelet pH was studied by the BCECF fluorescent pH-sensitive intracellular indicator method in 52 patients with essential hypertension and 42 control subjects of similar age and sex. In 40 hypertensive patients studied by oral glucose tolerance test (standard OGTT) 23 presented with pathological blood glucose and plasma insulin values. Intracellular pH was on average higher in hypertensives (7.415 +/- 0.114, mean +/- SD) than in controls (7.348 +/- 0.109, P < 0.05), although there was a considerable overlap in values. In the group of hypertensive patients, no difference was observed between those with normal and those with pathological OGTT. There was also no significant correlation between intracellular pH and blood glucose, plasma insulin after OGTT, plasma cholesterol and triglycerides, age, BP or body mass index. These data are consistent with an anomaly of intraplatelet pH, perhaps owing to alteration of Na+/H+ exchange in essential hypertension, but do not indicate that this is related to a condition of hyper-insulinaemia or insulin resistance. PMID- 8450520 TI - Effect of oral calcium supplementation on blood pressure in patients with previously untreated hypertension: a randomised, double-blind, placebo controlled, crossover study. AB - It has been claimed that calcium lowers BP. The present randomised, double-blind, placebo-controlled crossover study is the first to investigate the effect on BP of a high oral dose of calcium given for a long period to patients with previously untreated hypertension. Elemental calcium (2 g) was administered for 12 weeks interchanging with a period of 12 weeks of placebo. Twenty patients completed the protocol. There was no significant difference in change of BP during the period of additional calcium intake when compared with placebo (P = 0.33). The risk of not detecting a real BP-lowering effect of calcium of at least 3 mmHg was < 5%. No evidence for the existence of a subgroup of 'responders' was found. It is concluded that a high daily dose of calcium supplementation given for 12 weeks does not decrease BP in previously untreated patients with mild to moderate hypertension. PMID- 8450521 TI - Calcium metabolism and sodium sensitivity in hypertensive subjects. AB - A pattern of negative calcium balanced with lowered levels of serum ionized calcium (Ca2+) and increased urinary excretion of calcium has been reported in hypertensive men. In the present study, ten untreated hypertensive subjects were salt loaded (20 g NaCl) for one week after a week on a low salt diet (< 3 g). The change in mean blood pressure (MBP) at the end of the high compared with the low salt diet was called salt sensitivity and was related to indexes of mineral metabolism. It was found that salt sensitivity was significantly correlated with both plasma ionized calcium (Ca2+) and serum calcium concentrations (both r = 0.64, P < 0.05) on the different diets. These relationships were strongest when sodium sensitivity was measured in the standing position during the low salt intake suggesting a role for an increased sympathetic tone. Salt loading increased the urinary excretion of calcium by 95% and also induced reductions in haemoglobin, serum albumin and serum calcium (P < 0.001). Ca2+, on the other hand, remained constant after salt loading. In conclusion, low levels of plasma ionized calcium and serum calcium were mainly found in hypertensive subjects with a low sensitivity to salt. Salt loading induced an increased calciuresis, haemodilution and possibly a shift of calcium from its protein-bound to its ionized form. The findings support the view that calcium metabolism is related to the regulation of BP. PMID- 8450522 TI - Altered calcium binding to erythrocyte membranes in essential hypertension: relation to magnesium. AB - Abnormal cellular ion transport resulting in altered membrane control over intracellular calcium may be aetiologically related to essential hypertension. Cell membrane calcium binding, which is influenced by magnesium, is an important membrane system involved in cellular calcium regulation. In this study the relationships between erythrocyte calcium binding and extra- and intracellular calcium and magnesium concentrations were determined in essential hypertensive patients (52 black, 24 white) and normotensive controls (52 black, 26 white). Calcium depletion of the erythrocytes by MgCl2 and EDTA resulted in the removal of more calcium ions from the outer erythrocyte membrane in the hypertensive group compared with the normotensive group. This may be considered as evidence of increased calcium binding to the outer cell membrane in essential hypertension. Calcium binding was greater in the hypertensive males compared with the females. In black hypertensives, serum and erythrocyte magnesium concentrations were significantly increased. In white hypertensives, serum calcium was significantly decreased and erythrocyte calcium significantly raised. Serum and erythrocyte magnesium correlated inversely with the amount of calcium released from the membranes in the black hypertensive group. The results of this study suggest that changes in magnesium levels may contribute to altered cell membrane calcium binding in essential hypertension. PMID- 8450523 TI - Low predictive value of positive Osler manoeuvre for diagnosing pseudohypertension. AB - Pseudohypertension is a condition where indirectly determined BP (e.g. via sphygmomanometry) significantly overestimates actual intraarterial pressure. A patient who has a palpable, although pulseless, radial artery while the blood pressure cuff is inflated above systolic pressure, has a positive 'Osler sign'. This 'Osler manoeuvre' has been reported to predict the presence of pseudohypertension. To evaluate its importance in diagnosing pseudohypertension, 19 hypertensive patients deemed Osler-positive by at least two observers were studied. BP was determined indirectly using a stethoscope and mercury sphygmomanometer. Intraarterial pressure was determined by a brachial artery catheter-transducer-monitoring system. For both pressure-measurement techniques and each patient, six readings were averaged to give a single systolic and diastolic value. Mean arterial pressure was calculated as diastolic pressure plus one-third the pulse pressure. Pseudohypertension was defined as a sphygmomanometric mean pressure that exceeded intraarterial mean pressure by > or = 10 mmHg. In this group of 19 Osler-positive patients, stethoscope sphygmomanometry underestimated systolic and overestimated diastolic intraarterial pressure. For mean pressure, sphygmomanometry was > or = 10 mmHg higher than intraarterial in two patients and > or = 10 mmHg lower than intraarterial in three patients. Thus, while two patients had pseudohypertension, three could be considered to have pseudohypotension, defined as a condition where indirect blood pressure significantly underestimates intraarterial pressure. Accordingly, a positive Osler manoeuvre did not reliably predict the presence of pseudohypertension in this population. PMID- 8450524 TI - Cardiac variables and blood pressure as determinants of left ventricular inflow velocities. AB - The determinants of the left ventricular diastolic transmitral flow pattern, measured by use of Doppler velocimetry, were assessed in 40 patients referred for hypertension. The ratio of the atrial to early filling peak velocity (A/E ratio) averaged 0.82 +/- 0.23, BP 156 +/- 19/100 +/- 13 mmHg and left ventricular mass 220 +/- 57. In multiple regression analysis the A/E ratio was independently and positively related to age (P < 0.001) and BP (P < 0.001) and inversely to the fractional shortening of the left ventricular internal diameter (P < 0.01) and left atrial size at end-systole (P < 0.05); these variables accounted for 71% of the variance of the A/E ratio. The peak flow velocity during atrial contraction was positively and independently related to age (P < 0.001), BP (P < 0.05) and heart rate (P < 0.05); early filling velocity decreased with age (P < 0.001) and was positively related to heart rate (P < 0.01), left atrial diameter (P < 0.01) and fractional shortening (P < 0.001). The weak positive associations of the A/E ratio with left ventricular mass (r = 0.32; P < 0.05) and wall thickness (r = 0.38; P < 0.05) did not persist in multiple regression analysis. In conclusion, the left ventricular diastolic filling indexes are related to age, BP, left atrial size and to systolic left ventricular function but left ventricular structural variables, as measured by echocardiography, are not significantly involved. PMID- 8450525 TI - Unilateral juxtaglomerular hyperplasia, hyperreninism and hypokalaemia relieved by nephrectomy. AB - Two women with spontaneous hypokalemia (1 normotensive, 1 hypertensive in the absence of renal artery stenosis), underwent unilateral nephrectomy because of angiographic and/or split renin-based suspicion of a reninoma. The normotensive patient clinically resembled Bartter syndrome but had some elements suggestive of a renin-secreting tumour, justifying surgical exploration and resection. The hypertensive patient presented clinically as a typical reninoma except for negative angiography. Surprisingly, the histology of the kidneys in both cases demonstrated juxtaglomerular hyperplasia without evidence of reninoma. The postoperative follow-up (8 and 19 yrs, respectively) has shown in the normotensive patient a considerable improvement in the hyper-reninism and previously uncontrollable hypokalaemia and in the hypertensive patient a complete normalisation of BP, renin and electrolyte status. Although the histological condition of the contralateral kidneys remains unknown in both patients the preoperative lateralisation of hyper-reninism to one kidney, the postoperative complete relief of the hyper-reninism in the hypertensive patient after uninephrectomy and its decrease, exceeding that corresponding to the removal of one kidney in the normotensive patient, suggest that the juxtaglomerular hyperplasia might have been unilateral or asymmetrical and that nephrectomy may, unexpectedly, relieve the hyper-reninism caused by juxtaglomerular hyperplasia. An increased unilateral susceptibility to trophic or renin-releasing factors or an asymmetrical abnormality in the macula densa-initiated mechanism of juxtaglomerular hyperplasia may be implicated in this disorder. PMID- 8450526 TI - Early side-effects of antihypertensive therapy: comparison of amlodipine and nifedipine retard. AB - In a multicentre crossover study of 97 patients with mild hypertension, the incidence and severity of adverse effects were observed during the first 14 days of treatment with amlodipine, nifedipine retard or placebo. Amlodipine (5 mg) once daily was equipotent to nifedipine retard (20 mg) twice daily. At these doses, the incidence of adverse effects was significantly greater during treatment with nifedipine retard (41%) than with amlodipine (27%, P < 0.05) or placebo (16%, P < 0.01). In particular, headache and flushing occurred significantly less frequently during the first 14 days of treatment with amlodipine than with nifedipine retard. The lower incidence and reduced severity of vasodilatory side-effects associated with amlodipine resulted in fewer withdrawals during initiation of therapy (2 on amlodipine compared with 7 on nifedipine retard). PMID- 8450527 TI - Effects of atenolol withdrawal in patients on triple antihypertensive therapy. AB - The objective of this study was to examine the contribution of beta-blockade to antihypertensive treatment regimens including an angiotensin converting enzyme inhibitor or a calcium antagonist. The effects on BP control, adverse events, and plasma active renin concentration of removing atenolol from standard triple therapy (bendrofluazide and atenolol together with captopril or nifedipine) were assessed in a double-blind, randomised, parallel-group study, of eight weeks' duration in 46 patients from the Glasgow Blood Pressure Clinic. Blood pressures rose in patients randomised to placebo-atenolol compared with those who continued active-atenolol although the difference did not achieve statistical significance. However, the proportion of patients with controlled blood pressure (supine systolic BP < 140 mmHg plus supine diastolic BP < 95 mmHg) fell from 31% to 0% over the study period in patients given placebo-atenolol. There was a trend for BP control to deteriorate most when atenolol was withdrawn from nifedipine treated patients, but the 95% confidence intervals for the difference from captopril-treated patients were wide. Few side-effects were seen and these did not differ quantitatively between the study groups. Plasma active renin concentration was initially higher in captopril-treated patients, and increased on withdrawal of atenolol in both groups. Our findings suggest that beta-blockers make a clinically relevant contribution to treatment regimens including angiotensin converting enzyme inhibitors or calcium antagonists when given as part of standard triple antihypertensive therapy. PMID- 8450528 TI - On the role of the P-site in leftward ribosome frameshifting at a hungry codon. AB - Previous work characterized ribosomal frameshifting within the sequence C UUC AAG provoked by lysyl-tRNA limitation. The ribosome frameshift is one base to the left of the AAG lysine codon, as shown by dotted overlining above. We now show that the frequency of this leftward ribosome frameshift is strongly influenced by the identity of the bases two, three and four positions to the left of the actual frameshift site. The nature of these influences coincides exactly with the possibilities of base-pairing between the sequence and the anticodon of the P site peptidyl-tRNA when shifted one base to the left just upstream of the frameshift site. We conclude that a peptidyl shift in the P-site is intimately involved in leftward frameshifting in the adjacent A site when it codes for an aminoacyl-tRNA in short supply. PMID- 8450529 TI - Hydrogen-bonding contacts in the major groove are required for human immunodeficiency virus type-1 tat protein recognition of TAR RNA. AB - The binding site for tat on TAR RNA was analysed by preparing a series of model RNA substrates carrying site-specific functional group modifications. The test RNAs were prepared by annealing two short synthetic oligoribonucleotides to form a duplex structure with a U-rich bulge and flanking sequences identical to TAR RNA. Tat binds these duplex RNAs with approximately half the affinity for wild type TAR RNA. Substitution at positions U23 or U25 by the base analogue, O4 methyl-dT, which is deficient in its ability to hydrogen-bond at the N3 position reduces tat affinity more than 20-fold. Modifications to purines in the stem of TAR RNA that affect hydrogen-bonding ability in either the major or the minor groove of duplex RNA were also tested. Removal of the nitrogen atom at either the N7 position of G26 or at the N7 position of A27 reduces tat affinity 10- to 20 fold. By contrast removal of the exocyclic amino group in the minor groove at position G26, by substitution with inosine, does not affect tat binding significantly. A single methylphosphonate substitution at the phosphate bond between A22 and U23 also leads to a significant loss of tat binding ability, whereas all other methylphosphonate substitutions in the U-rich bulge are not harmful to tat binding. We conclude that tat forms multiple specific hydrogen bonds to a series of dispersed sites displayed in the major groove of the TAR RNA molecule. These include the N3-H of U23, the N7 of G26, the N7 of A26 and the phosphate between A22 and U23. PMID- 8450530 TI - Zinc finger mutations that alter domain interactions in the glucocorticoid receptor. AB - The DNA binding domain of steroid receptors coincides with the cysteine-rich region encompassing the two conserved zinc fingers. In the case of the glucocorticoid receptor (GR), a weak transactivation function has been described to be adjacent or partly overlapping to the DNA binding domain, whereas stronger trans-acting functions are encoded by the amino and the carboxy domain. In this report we describe the phenotype produced by stochastic mutations of the zinc finger region. The mutants were obtained either by selected rearrangements of the rat GR cDNA, or by semi-random nucleotide substitutions. All the identified permissive rearrangements were confined to a region downstream from the first zinc finger (duplications starting between residue 474 and 492). In general, the phenotype of point mutations is compatible with established structural data. Nevertheless, we found two unexpected phenotypes. First, we noticed that the double mutant His451 Asn/Ser459Gly is stronger than the wild-type sequence in DNA binding. Secondly, substitution of the conserved Lys461 results in an abnormal behavior of the mutated GR. In particular, the mutant Lys461Tyr (61Y) displays about the same transactivation when tested in form of a minimal GR fragment (amino acids 407/556) as when tested in the amino-prolongued GR fragment (amino acids 3-556, which contains the major transactivation domain of the GR). This is in contrast with the behavior of the other mutants in which the residue 461 is intact. In these cases, transactivation capacity is normally increased more than 30-fold from GR407-556 to GR3-556. These results are discussed in terms of possible cross-talk among the DNA binding domain and other functions residing in the amino domain of the GR. PMID- 8450531 TI - Structural patterns at residue positions 9, 18, 67 and 82 in the VH framework regions of human and murine immunoglobulins. AB - VH framework regions of human and mouse immunoglobulins display three characteristic patterns in the conformation of the main polypeptide chain and side-chains at residue positions 9, 18, 67 and 82. These structural patterns are associated with the amino acid sequence at positions 9 and 67. Human and murine VH sequences show a strong correlation between the occurrence of Gly at position 9 and Phe at position 67 in VH subgroup III, and the frequent occurrence of Pro, Ala or Ser at position 9 and a non-aromatic residue at position 67 in other VH subgroups. Variations in VH framework segments have been shown to be of importance in procedures to humanize monoclonal murine antibodies and may be involved in the conformation of epitopes recognized by anti-VH antibodies. The structural patterns described here can be expected to influence the results of rotation and translation search functions in the crystallographic structure determination of Fab and Fv fragments by the molecular replacement method. PMID- 8450532 TI - Negative and positive regulators modulate the activity of a silkmoth chorion gene during choriogenesis. AB - We have used in vitro linker substitution mutagenesis and P-element-mediated transformation in Drosophila to define cis-regulatory elements of the bidirectional promoter of the Bombyx mori A/B.L12 chorion genes in an in vivo situation. Within an essential 112 bp part of this promoter, mutations in two non contiguous approximately 35 base-pair regions (A1 and A2) result in significant reduction of expression at late choriogenesis. The reduction occurs in both promoter orientations, indicating the existence of bidirectionally active positive elements. Mutations in A1, but not in A2, also lead to premature activation at early choriogenesis, suggesting the existence of a negative element essential for the finely tuned expression profile during choriogenesis. Normally, this element apparently prevents early expression; it also acts bidirectionally. The highly specific effects of these mutations suggest that several trans-acting regulators of chorion gene transcription have been conserved between silkmoths and fruitflies. PMID- 8450533 TI - In vivo thermodynamic analysis of repression with and without looping in lac constructs. Estimates of free and local lac repressor concentrations and of physical properties of a region of supercoiled plasmid DNA in vivo. AB - A strong-binding primary (O1) lac operator located 100 to 200 base-pairs (bp) upstream from a lac promoter control region reduces expression from a lac promoter controlled by a weaker-binding (Oc) lac operator between 3 and 20-fold on a multicopy plasmid in E. coli. We attribute this effect to loop formation in which a thermodynamically stable complex is formed between bidentate lac repressor tetramers and the O1 and Oc operators. A thermodynamic model for repression is developed to interpret these data in terms of the composite effects of free lac repressor concentration and of local repressor concentration (from looping) at the Oc site. The local repressor concentration is found to vary periodically with the distance in base-pairs between the O1 and the Oc operators, ranging from 2 to 20-fold larger than the free concentration (i.e. the bulk thermodynamic activity) of repressor in this F'Iq overproducing strain (estimated to be approximately less than 0.5 microM). The amplitude of the periodic variation in expression and in local concentration appears to decrease with increasing interoperator distance in the range examined. Quantitative analysis of the looping data provides estimates of the physical properties of the intervening DNA region in vivo. For distances in the range 127 to 197 bp, the periodicity of modulation is uniformly 11.28(+/- 0.04) bp, which we interpret as the helical repeat of this region of supercoiled plasmid DNA in vivo. Possible origins of this altered helical repeat include the global linking deficit of the supercoiled DNA and any local linking deficit induced by divergent transcription from promoters bracketing the interoperator region. DNA cyclization analysis yields an apparent in vivo persistence length of this interoperator region of 64(+/- 26) A (which is approximately 15% of the in vivo result) and an in vivo torsional rigidity constant of 1.1(+/- 0.1) x 10(-19) erg cm, which is at the lower end of the range of values found in vitro. PMID- 8450534 TI - Precise deletions in large bacterial genomes by vector-mediated excision (VEX). The trfA gene of promiscuous plasmid RK2 is essential for replication in several gram-negative hosts. AB - We have developed a simple and efficient method of vector-mediated excision (VEX) for in vivo generation of precisely defined deletions in large bacterial genomes. The system uses homologous recombination with small cloned fragments on specialized pVEX plasmids to insert directly repeated bacteriophage P1 loxP sites at positions flanking the region to be deleted. In the presence of Cre recombinase, the loxP sites are efficiently recombined to produce the deletion. Deletion endpoints can be directed to specific nucleotides because they are defined by the termini of small homology-bearing fragments cloned into the pVEX plasmids. We have used VEX to delete trfA, the only known replication initiator gene of the 56.4 kb broad host-range plasmid RK2. The RK2 delta trfA mutant was found to be conjugation proficient, but unable to replicate in the RK2 hosts Acinetobacter calcoaceticus, Caulobacter crescentus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Pseudomonas putida, Rhizobium meliloti, or Rhodobacter sphaeroides. These results show that trfA is essential for replication in these hosts and indicate that the broad host-range of RK2 does not involve multiple replicons. PMID- 8450535 TI - Normal mode analysis of G-actin. AB - We undertook a normal mode analysis of the G-actin monomer bound with ADP and Ca2+, in order to better understand the internal modes of this protein. The internal co-ordinates consisted of 1373 single bond torsions, plus an additional 11 torsions to parameterize the motion of the nucleotide and cation with respect to the protein. A generalized eigenvalue problem was solved to yield a complete description of the motion in the 0.1 to 17.0 picosecond time range. The modes were visualized using an interactive graphics routine. The softest, slowest modes include a propeller-like twisting of the large and small domain about the phosphate binding loops, a rolling of subdomain 4 about an alpha-helix axis and a scissor-type opening and closing of the ADP-binding cleft. The computed temperature factors agree well with experimental ones. A comparable analysis done on G-actin-ATP shows that the softest modes are almost identical. PMID- 8450536 TI - Projection image of smooth muscle alpha-actinin from two-dimensional crystals formed on positively charged lipid layers. AB - Two-dimensional crystalline arrays of chicken gizzard alpha-actinin have been formed on positively charged lipid layers. This is the first reported crystallization of alpha-actinin. The crystals have unit cell dimensions of a = 248 A, b = 194 A, y = 106 degrees and contain two alpha-actinin molecules. The two-sided group is P21. Projection images obtained from electron micrographs of negatively stained crystals have been calculated to a resolution of 25 A. These images reveal a complex substructure. The molecule in projection is 340 A in length and has 12 density peaks that probably correspond to protein domains. A pair of peaks is found at each end of the molecule, these probably correspond to the actin binding region. Eight peaks are observed in the central, rod-shaped region, these may correspond to the spectrin-like repeats predicted from the amino acid sequence. However, these eight central peaks are not arranged in four pairs but, instead, consist of three central pairs flanked at either end by a single peak, which appears larger and denser in projection than the three central pairs. The individual alpha-actinin molecules in projection lack 2-fold symmetry suggesting that either smooth muscle alpha-actinin lacks a molecular 2-fold symmetry axis or that the molecular 2-fold is not parallel with the crystallographic 2-fold axis. The ends of the molecule have different appearance in projection, suggesting that the molecule is twisted about the long axis. A hypothesis is proposed to explain the variations in molecular length and Ca2+ sensitivity between alpha-actinin isoforms. PMID- 8450537 TI - Molecular basis of allosteric activation of bacterial L-lactate dehydrogenase. AB - The three-dimensional structure of allosteric L-lactate dehydrogenase from Bifidobacterium longum, the first example of a T-state structure of L-lactate dehydrogenase, has been determined to 2.0 A. A comparative study of this structure with the previously reported R-state structure from Bacillus stearothermophilus has revealed the allosteric activation mechanism of the bacterial L-lactate dehydrogenase. The fructose 1,6-bisphosphate-induced conformational change at the effector site and the substrate affinity change at the activity site are clearly shown at a molecular level. Coupling of these changes can be simply explained by a set of concerted rotations between subunits in the tetramer of the enzyme. This T to R transition is the first example for a tetrameric allosteric protein where the rotations occur around each of three axes of symmetry. PMID- 8450538 TI - Refined structure of Sindbis virus core protein and comparison with other chymotrypsin-like serine proteinase structures. AB - Crystal forms 2 and 3 of Sindbis virus core protein have been refined to 2.8 A and 3.0 A resolution, respectively. The three independent molecular copies in the two crystal forms are essentially identical, except for regions where the molecules are involved in different crystal packing interactions. The overall polypeptide backbone fold of Sindbis virus core protein is similar to other chymotrypsin-like serine proteinase structures despite a lack of significant sequence homology. Detailed analysis revealed differences in the catalytic triad and the substrate binding pockets between the Sindbis virus core protein and the other serine proteinases. The catalytic aspartic acid residue (Asp163) and residue Asp214 (corresponding to Asp194 in chymotrypsin) are partially exposed to solvent in Sindbis virus core protein. Chymotrypsin Ser214, hydrogen bonded to the catalytic aspartic acid residue in all other serine proteinase structures, is changed to Leu231 in Sindbis virus core protein. Deletions in the loop regions on the surface of the protein account for the smaller size of the ordered part of Sindbis virus core protein (151 residues) as compared to chymotrypsin (236 residues), and permits the cis autocatalytic cleavage of the polyprotein to produce the viral capsid protein. PMID- 8450539 TI - Superhelical path of the DNA in the nucleoprotein complex that activates the initiation of phage phi 29 DNA replication. AB - Initiation of bacteriophage phi 29 DNA replication is activated by protein p6, a viral double-stranded DNA-binding protein that forms a nucleoprotein complex at the viral replication origins. This complex consists of a DNA right-handed superhelix wrapped around a multimeric protein p6 core with protein p6 dimers regularly bound every 24 base-pairs (bp). In this paper, we have constructed a concatemer formed by direct repeats of a 24 bp sequence previously proposed to act as a signal for protein p6 binding at a phi 29 replication origin. DNase I footprinting shows that protein p6 binds to the concatemer in a similar way to the phi 29 DNA replication origins but with higher affinity, indicating that the 24 bp sequence is a recognition signal for protein p6. Furthermore, the concatemer was cloned in a plasmid and, by electron microscopy, it was shown to be the highest-affinity protein p6 binding region present in the plasmid. Based on these observations, the linking number change restrained by protein p6 has been measured in a series of plasmids containing concatemers with different numbers of 24 bp repeats; from the values obtained the linking number change restrained by a single protein p6 dimer has been estimated (delta Lkd = 0.1). In addition, when protein p6-DNA complexes fixed with glutaraldehyde were analysed by electron microscopy, it was observed that protein p6 compacts 4.2-fold the length of naked DNA. These data, together with the previously known value of the surface-related DNA helical repeat in the complex (12 bp), completely define the superhelical path of the DNA in the complex: one superhelical turn approximately involves 63 bp and 2.6 protein p6 dimers, and the DNA superhelix has a diameter of 6.6 nm and a slope of 14 degrees. The data obtained also indicate that the DNA in the protein p6-DNA complex is undertwisted (11.5 bp/turn) and strongly bent (66 degrees/12 bp). These DNA conformational changes might contribute to the activation of phi 29 DNA initiation of replication by protein p6. PMID- 8450540 TI - X-ray analyses of aspartic proteinases. V. Structure and refinement at 2.0 A resolution of the aspartic proteinase from Mucor pusillus. AB - The structure of mucor pusillus pepsin (EC 3.4.23.6), the aspartic proteinase from Mucor pusillus, has been refined to a crystallographic R-factor of 16.2% at 2.0 A resolution. The positions of 2638 protein atoms, 221 solvent atoms and a sulphate ion have been determined with an estimated root-mean-square (r.m.s.) error of 0.15 to 0.20 A. In the final model, the r.m.s. deviation from ideality for bond distances is 0.022 A, and for angle distances it is 0.050 A. Comparison of the overall three-dimensional structure with other aspartic proteinases shows that mucor pusillus pepsin is as distant from the other fungal enzymes as it is from those of mammalian origin. Analysis of a rigid body shift of residues 190 to 302 shows that mucor pusillus pepsin displays one of the largest shifts relative to other aspartic proteinases (14.4 degrees relative to endothiapepsin) and that changes have occurred at the interface between the two rigid bodies to accommodate this large shift. A new sequence alignment has been obtained on the basis of the three-dimensional structure, enabling the positions of large insertions to be identified. Analysis of secondary structure shows the beta-sheet to be well conserved whereas alpha-helical elements are more variable. A new alpha-helix hN4 is formed by a six-residue insertion between positions 131 and 132. Most insertions occur in loop regions: -5 to 1 (five residues relative to porcine pepsin): 115 to 116 (six residues); 186 to 187 (four residues); 263 to 264 (seven residues); 278 to 279 (four residues); and 326 to 332 (six residues). The active site residues are highly conserved in mucor pusillus pepsin; r.m.s. difference with rhizopuspepsin is 0.37 A for 25 C alpha atom pairs. However, residue 303, which is generally conserved as an aspartate, is changed to an asparagine in mucor pusillus pepsin, possibly influencing pH optimum. Substantial changes have occurred in the substrate binding cleft in the region of S1 and S3 due to the insertion between 115 and 116 and the rearrangement of loop 9-13. Residue Asn219 necessitates a shift in position of substrate main-chain atoms to maintain hydrogen bonding pattern. Invariant residues Asp11 and Tyr14 have undergone a major change in conformation apparently due to localized changes in molecular structure. Both these residues have been implicated in zymogen stability and activation. PMID- 8450541 TI - The bacteriophage 434 right operator. Roles of O(R)1, O(R)2 and O(R)3. AB - Lysogenic induction of bacteriophage lambda is controlled by the action of the phage repressor and Cro proteins at the phage right operator (O(R)). This study examines the roles of the repressor and Cro proteins of the related phage 434. The start sites of transcription of the divergently oriented promoters in the 434 O(R) region, PR and PRM, were mapped, and the effects of 434 repressor and Cro on promoter activity were assessed using promoter fusions to lacZ. The effects of repressor or Cro bound to each of the operator subsites (O(R)1, O(R)2 and O(R)3) were assessed by examining regulation in the presence of operator mutations. The binding of Cro to a 434 operator was probed by an ethylation interference experiment which, together with other data, indicates that 434 Cro and repressor probably turn off transcription by blocking binding of RNA polymerase to promoter sequences. In general, the 434 and lambda right operators are controlled in a similar fashion, but differences in detail were also encountered: (1) 434 Cro represses transcription from PR primarily by binding to O(R)1, whereas binding of lambda Cro to O(R)1 and O(R)2 contribute equally to repression. (2) The 434 cI message, unlike that of lambda, has a recognizable homology to the Shine-Dalgarno ribosome binding site. (3) Occupancy of O(R)3 by repressor may be somewhat greater in a 434 lysogen than in a lambda lysogen. (4) The 434 repressor probably activates transcription when bound at O(R)2 by contacting RNA polymerase, as does lambda repressor, but also by influencing competition between PR and PRM. An analysis of the six right operator systems for which data are available indicates that all six repressors may employ the mechanism of transcriptional activation first described for lambda, P22 and 434: apposition of an acidic surface to a particular part of RNA polymerase. PMID- 8450542 TI - The (i, i + 4) Phe-His interaction studied in an alanine-based alpha-helix. AB - Two models have been considered for the helix-stabilizing Phe-His+ interaction in C-peptide: (1) the H-bond model in which His+ acts as an H-bond donor and the aromatic ring of Phe acts as an acceptor, and (2) a helix dipole model, in which Phe constrains His so that there is a stronger interaction between His+ and the helix dipole. To decide between these models, we compared the effect on helix stability of the Phe-His interaction near the middle versus close to the C terminus of an alanine-based peptide. The nature of the interaction is the same at either position, in agreement with the H-bond model. The results show further that a weak helix-stabilizing Phe-His interaction can be detected when His is uncharged. Replacement of Phe by the saturated analog Cha (beta cyclohexylalanine) gives no interaction, as predicted by the H-bond model. PMID- 8450543 TI - Atomic resolution (0.83 A) crystal structure of the hydrophobic protein crambin at 130 K. AB - To enhance the already high quality of diffraction data for crystals of the hydrophobic protein crambin, X-ray data were collected at 130 K by the method of H. Hope to 0.83 A resolution. Refinement with PROLSQ yields a model with an R value of 10.5%. The final model had three parameter anisotropic vibration factors for all atoms, which included 367 protein heavy atoms, 372 hydrogen atoms and 144 solvent atoms with one ethanol molecule. Dihedral angles and hydrogen-bonding distances generally agree with earlier studies of high-resolution protein structures, but some new patterns are noted. Solvent-related helix distortions are reminiscent of those described by others. Helix and beta-sheet regions show distinct patterns in their side-chain conformations. Despite crambin's hydrophobic nature, its accessible surface area in the crystal is surprisingly close to that of water-soluble proteins like myoglobin and carboxypeptidase A. More of crambin's hydrophobic surface is buried in the crystal, perhaps accounting for its high order of diffraction. A total of 24% of the 46 residues show discrete disorder at 130 K. This includes five side-chains at both 300 and 130 K, and six more side-chains and an ethanol molecule at 130 K. Disorder is associated with the sequence microheterogeneity at Pro/Ser22 and Leu/Ile25, with space filling or with solvent disorder. Correlated conformations extend over three to five residues. The patterns of disorder in this structure reveal important principles of protein structure and its dynamics. Finding disordered groups correlated over 5 to 8 A suggests that co-ordinated motion extends in groups rather than simply as uncorrelated movement around an atom center. Thermal diffuse scattering experiments on insulin and lysozyme are consistent with this interpretation. Nearly all of the protein-bound solvent has been located. Less than 1% of protein accessible surface area remains uncovered by solvent or crystal contacts. Preliminary analysis of the solvent network reveals two main networks in each of four solvent regions. PMID- 8450544 TI - The high-resolution structure of the peripheral subunit-binding domain of dihydrolipoamide acetyltransferase from the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus. AB - The three-dimensional structure of a 43-residue active, synthetic peptide encompassing the peripheral subunit-binding domain of dihydrolipoamide acetyltransferase from the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus has been determined by means of a multi-cooling dynamical simulated annealing protocol using restraints derived from 1H nuclear magnetic resonance spectroscopy. A total of 442 experimentally derived restraints including 13 dihedral angle (phi, chi 1) restraints were used. A final set of 35 structures was calculated with a root-mean-square deviation from the mean co ordinates of 0.36 A for the backbone atoms and 0.96 A when side-chain heavy atoms were included for the well-defined region comprising residues Val7 to Leu39. Although assignments were made and sequential connectivities observed for the N terminal six and C-terminal four residues, the absence of long-range NOEs suggests that the terminal regions are largely unstructured. The binding domain contains two short parallel alpha-helices (residues Val7 to Lys14 and Lys32 to Leu39), a3(10)-helix (residues Asp17 to Val21) and a structured loop made up of overlapping beta-turns (residues Gln22 to Leu31), which enclose a close-packed hydrophobic core. The loop is stabilized to a large extent by Asp34. This residue is conserved in all peripheral subunit-binding domains and its carboxylate side chain forms a set of side-chain-main-chain hydrogen bonds with the main-chain amide protons of Gly23, Thr24, Gly25 and Leu31 and a side-chain-side-chain hydrogen bond with the hydroxyl group of Thr24. We propose that a peripheral subunit-binding site may be located in the loop region, which contains a series of highly conserved residues and provides a number of potential recognition sites. The structured region of the binding domain, comprising 33 residues, represents an exceptionally short amino acid sequence with defined tertiary structure that has no disulphide bond, ligand or cofactor to stabilize the fold. It may be approaching the lower size limit for a three-dimensional structure possessing features characteristic of larger structures, including a close packed, non-polar interior. The organization of the side-chains in the hydrophobic core may have implications for de novo protein design. PMID- 8450545 TI - Crystallization and preliminary crystallographic analysis of Streptomyces griseus aminopeptidase. AB - Streptomyces griseus excretes a small molecular mass (30 kDa) aminopeptidase that could be used for various biotechnological applications. This enzyme was isolated from an extracellular protease mixture of Streptomyces griseus (Pronase E. Sigma) and single crystals were obtained by the vapor diffusion method using polyethylene glycol 4000 as the precipitant. The crystals belong to the tetragonal space group P4(1)2(1)2 (P4(3)2(1)2), with cell dimensions of a = b = 61.82(3) A and c = 145.88(4) A. These crystals are mechanically strong, they are stable in the X-ray beam and they diffract to better than 1.8 A resolution. The cell dimensions and the cell symmetry are consistent with one molecule in the asymmetric unit and the crystals are suitable for a detailed high-resolution crystallographic analysis. A complete native data set to 1.9 A resolution has been collected on a Rigaku R-AXIS-IIC Imaging Plate Detector system and a heavy atom derivative search is in progress. PMID- 8450546 TI - Crystallization and preliminary X-ray studies of influenza A virus neuraminidase of subtypes N5, N6, N8 and N9. AB - Neuraminidase heads from the following subtypes of influenza A virus have been crystallized: N5, N6, N8 and whale virus N9. The last three yielded crystals of X ray diffraction quality; the N5 crystals obtained so far are not suitable for high resolution studies. The cell dimensions and space groups of crystals grown from the four subtypes have been determined. PMID- 8450547 TI - Crystallization of the major coat protein of PRD1, a bacteriophage with an internal membrane. AB - The major multimeric coat protein, P3, of the bacterial virus PRD1 has been crystallized by vapor diffusion from polyethylene glycol 4000. The PRD1-P3 crystals belong to the orthorhombic space group P2(1)2(1)2(1) with unit cell dimensions a = 121.6 A, b = 123.2 A, c = 128.6 A and diffract to 3.0 A resolution. Density measurements show that there is one trimer (3 x 43.1 kDa) per asymmetric unit and a high solvent content of 67%. A self-rotation function calculation shows a pronounced peak indicating a non-crystallographic threefold axis. This indicates that the major viral capsomer is a trimer and allows the viral T-number to be postulated. PMID- 8450548 TI - Crystal parameters of an alcohol dehydrogenase from the extreme thermophile Thermoanaerobium brockii. AB - A bacterial thermophilic alcohol dehydrogenase which is stable and active at 85 degrees C, has been crystallized by vapor diffusion from solutions of polyethylene glycol. A monoclinic crystal form diffracts to 2.8 A resolution and belongs to space group C2 with unit cell dimensions a = 139.0 A, b = 137.4 A, c = 80.9 A and beta = 93.23 degrees. The asymmetric unit contains four molecules which exhibit 222 point symmetry. A second crystal form is orthohombic, space group P2(1)2(1)2 with unit cell dimensions a = 168.0 A, b = 123.0 A, c = 80.0 A, and it diffracts to 3.2 A resolution. PMID- 8450549 TI - Release factor-dependent false stops are infrequent in Escherichia coli. AB - We have estimated the frequency of release factor dependent events in which a sense codon is mistakenly translated as a stop codon. We refer to this event as a "false stop". In order to facilitate the measurement of false stop freqeuncies we have used a plasmid expression system to increase individually the cellular levels of release factor (RF) I a and of release factor (RF) 2. We were then able to measure the loss of translational processivity with the aid of a lacZ processivity assay at different concentrations of the release factors. We find that a 30- to 40-fold increase of the RF1 concentration reduces lacZ processivity from 0.6 to 0.3. Assuming that the processivity loss is due only to false stops and that the RF1 overproduction data can be extrapolated back linearly to the normal RF1 concentration in the cell, this corresponds to a false stop frequency close to 10(-5) per codon in the presence of normal amounts of RF1. Furthermore, a threefold increase of the RF2 concentrations had no measurable effect on the processivity of the lacZ gene. Our data suggest that false stops are relatively infrequent compared to the incidence of other translation errors. PMID- 8450550 TI - Unassigned or nonsense codons in Micrococcus luteus. AB - We previously reported that in Micrococcus luteus, a Gram-positive eubacterium with high genomic G + C content, certain codons ending with A did not appear in coding frames, including termination sites, and tRNAs that translate these codons were not detected. These facts suggest that at least some of them are unassigned (nonsense) codons, i.e. not assigned to any amino acid or to any stop signal. We have investigated whether AGA and AUA, universal Arg and Ile codons, respectively, are really unassigned codons by using a cell-free extract prepared from M. luteus and synthetic messenger RNAs. Translation of synthetic mRNA containing in-frame AGA codons does not result in "read-through" to codons beyond the AGA codons, i.e. translation ceases at codon AGA. Essentially the same result was obtained with mRNA containing AUA in-frame. A sucrose-gradient centrifugation profile of the reaction mixture has shown that practically all of the peptides that have been synthesized are attached to 70 S ribosomes. When in-frame AGA or AUA codons are replaced by UGA codons in mRNA, no read-through occurs beyond UGA, just as in the case of AGA or AUA. However, the synthesized peptide is released from the 70 S ribosomes. These data suggest that AGA and AUA are unassigned codons and differ from UGA in that they are not used for termination. PMID- 8450551 TI - Gene organization, primary structure and RNA processing analysis of a ribosomal RNA operon in Lactococcus lactis. AB - Southern blot analysis of genomic DNA of the mesophilic lactic bacterium Lactococcus lactis subsp. lactis strain IL1403, illuminated six rRNA gene clusters. Each cluster contains one copy each of three rRNA genes, displaying the typical eubacterial organization of physically linked 16 S, 23 S and 5 S rRNA genes. Five of the six rRNA clusters were cloned into plasmid pBR322. One recombinant plasmid, pSLCM6, containing a 6500 base-pair genomic DNA fragment, was characterized by physical mapping and the sequences encoding rRNAs and tRNAs were localized by Southern hybridization. This fragment contains a single operon composed of one promoter, a leader sequence, a 16 S rRNA gene, a tRNA(Ala) gene, a 23 S rRNA gene, a 5 S rRNA gene and a tRNA(Asn) gene. S1 nuclease mapping and primer extension analysis of in vivo transcripts localized one transcriptional initiation site 150 base-pairs upstream from the start of the 16 S rRNA gene. These procedures also suggest that this transcript is processed by an RNAse III like activity similar to Bacillus subtilis; i.e. the L. lactis nuclease might be sequence-specific. The chronology of specific cleavages occurring during the maturation process of the precursor transcript is described. One interesting observation is that the regions flanking the 16 S and 23 S rRNAs containing the primary processing sites are identical and contain sequences that could be involved in transcriptional antitermination. S1 mapping of the 3' ends of in vivo transcripts indicate that a terminator-like sequence a few base-pairs downstream from the distal tRNA(Asn) gene is inefficient in arresting transcription. PMID- 8450552 TI - Base-pair induced shifts in the tautomeric equilibrium of a modified DNA base. AB - We have examined the base-pairing properties of N4-methoxycytosine (mo4C), a mutagenic base analog, in DNA by nuclear magnetic resonance spectroscopy. Unlike standard bases, the tautomeric equilibrium of mo4C could be strongly influenced by base-pair formation. Paired with A, mo4C is found predominantly in the imino configuration in Watson-Crick geometry. However, when paired with G, two structurally distinct configurations are observed in equilibrium with one another. In one configuration, mo4C is in the amino form paired with G in Watson Crick geometry. In the second species, mo4C is in the imino configuration paired with G in a wobble geometry. This is the first demonstration of basepair induced tautomeric shifts in DNA and supports the hypothesis that rare tautomeric forms may be involved in mutagenesis. PMID- 8450553 TI - High affinity binding of TAR RNA by the human immunodeficiency virus type-1 tat protein requires base-pairs in the RNA stem and amino acid residues flanking the basic region. AB - The binding site for tat protein on TAR RNA has been defined in quantitative terms using an extensive series of mutations. The relative dissociation constants for the mutant TAR RNAs were measured using a dual-label competition filter binding assay in which 35S-labelled wild-type TAR RNA (K1) was competed against 3H-labelled mutant TAR RNA (K2). The error in the self-competition experiment was usually less than 10% (e.g. K2/K1 = 1.07 +/- 0.05, n = 19) and the experimental data accurately matched theoretical curves calculated with fitted dissociation constants. Mutations in U23, a critical residue in the U-rich "bulge" sequence, or in either of the two base-pairs immediately above the "bulge", G26.C39 and A27.U38 reduced that affinity by 8- to 20-fold. Significant contributions to tat binding affinity were also made by the base-pairs located immediately below the bulge. For example, mutation of A22.U40 to U.A reduced tat affinity 5-fold, and mutation of G21.C41 to C.G reduced tat affinity 4-fold. The binding of a series of peptides spanning the basic "arginine-rich" sequence of tat was examined using both filter-binding and gel mobility shift assays. Each of the peptides showed significantly reduced affinities for wild-type TAR RNA compared to the tat protein. The ADP-2 (residues 43 to 72), ADP-3 (residues 48 to 72) and ADP-5 (residues 49 to 86) peptides were unable to discriminate between wild-type TAR RNA and TAR RNA mutants with the same fidelity as the tat protein. For example, these peptides showed no more than 3-fold reductions in affinity relative to wild type TAR RNA for the U23-->C mutation in the bulge, or G26.G39-->C.G mutation in the stem of TAR RNA. By contrast, the ADP-I (residues 37 to 72), ADP-4 (residues 32 to 62) and ADP-6 (residues 32 to 72) peptides, which each carry amino acid residues from the "core" region of the tat protein have binding specificities that more closely resemble the protein. The ADP-4 and ADP-6 peptides showed between 4- and 7-fold reductions in affinity for the U23-->C or G26.C39-->C.G mutations. The ADP-1 peptide most closely resembles the protein in its binding specificity and showed 9-fold and 14-fold reductions in affinity for the two mutants, respectively. Chemical-modification interference assays using diethylpyrocarbonate (DEPC) and ethylnitrosourea (ENU) were also used to compare the binding properties of the tat protein and the tat-derived peptides.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8450554 TI - Lead in human blood and milk from nursing women living near a smelter in Mexico City. AB - Lead levels in breast milk and blood were determined in women living within a 200 m radius of 3 smelters in Mexico City. All samples were analyzed on a Perkin Elmer 460 atomic absorption spectrometer equipped with HGA 2200. The mean blood lead level was 45.88 micrograms/dl (SD 19.88 microgram/dl), and the geometric mean of milk lead level was 2.47 micrograms/100 ml. The correlation coefficient of these two variables was 0.88. Using the mean value of lead found in breast milk, an infant of 5.5 kg would ingest 8.1 micrograms/kg/d in his diet. The daily permissible intake (DPI) established by the World Health Organization (WHO) in 1972 for an adult is 5.0 micrograms/kg/d. PMID- 8450555 TI - Urinary excretion of unmetabolized benzene as an indicator of benzene exposure. AB - Benzene concentrations in urine samples (Cu, ng/L) from 110 workers exposed to benzene in chemical plants and gasoline pumps were determined by injecting urine supernate into a gas chromatograph. The urine was saturated with anhydrous N2SO4 to facilitate the passage of benzene in the air over the urine. The solvent was stripped from the urine surface and concentrated on an adsorbent substrate (Carbotrap tube) by means of a suction pump (flow rate 150 ml/m). Wash-up of the head space was achieved by simultaneous intake of filtered air through charcoal. Benzene was thermically desorbed and injected in a column (thermal tube disorder, Supelco; 370 degrees C thermal flash; borosilicate capillary glass column SPB-1, 60 m length, 0.75 mm ID, 1 microns film thickness; GC Dani 8580-FID). Benzene concentrations in the urine from 40 non-exposed subjects (20 smokers > 20 cigarette/d and 20 nonsmokers) were also determined [median value of 790 ng/L (10.17 nmol/L) and 131 ng/L (1.70 nmol/L), respectively]. The 8-h time-weighted exposure intensity (Cl, micrograms/m3) of individual workers was monitored by means of charcoal tubes. The median value for exposure to benzene was 736 micrograms/m3 (9.42 mumol/m3) [geometric standard deviation (GSD) = 2.99; range 64 micrograms/m3 (0.82 mumol/m3) to 13,387 micrograms/m3) (171.30 mumol/m3)]. The following linear correlation was found between benzene concentrations in urine (Cu, ng/L) and benzene concentrations in the breathing zone (Cl, micrograms/m3): log(Cu) = 0.645 x log(Cl) + 1.399 r = .559, n = 110, p < .0001 With exclusion of workers who smoked from the study, the correlation between air benzene concentration and benzene measured in urine was: log(Cu) = 0.872 x log(Cl) + 0.6 r = .763, n = 63, p < .0001 The study results indicate that the urinary level of benzene is an indicator of occupational exposure to benzene. PMID- 8450556 TI - Distribution of glass fibers in the peritoneal cavity of the rat following administration by intraperitoneal injection. AB - The distribution of glass fibers in the peritoneal cavity of the rat was investigated at 2, 24, and 48 h following intraperitoneal injection of 1 mg of material using a radioactive tracer technique. At each time point the peritoneal cavities of the rats killed were lavaged with 20 ml of physiological saline to recover fibers not yet attached to tissue surfaces. At 2 h, 35% of the administered fiber could be recovered by lavage, but at 48 h this was reduced to 2%. At 48 h, the amount of fiber associated with the abdominal organs and the abdominal wall was roughly in proportion to their surface areas. The weight of fiber associated with the various tissues was in the following order: gastrointestinal tract > liver > carcass (abdominal wall) > diaphragm > urogenital tract > spleen > kidneys. Differential counts on cells recovered by lavage were made both on cytocentrifuge slides and by flow cytometry. Compared with controls, the numbers of cells recovered from treated rats at 24 and 48 h were increased by a factor of about 2, due mainly to an influx of neutrophils into the peritoneal cavity. There was a marked reduction in the proportion of mast cells compared to controls. PMID- 8450557 TI - Strain comparisons of DFP neurotoxicity in rats. AB - The purpose of this study was to assess intraspecies differences in behavioral and autonomic function in three strains of rat following administration of diisopropyl fluorophosphate (DFP), an irreversible inhibitor of acetylcholinesterase activity. Male rats of the Long-Evans (LE), Fischer 344 (F344), and Sprague-Dawley (SD) strains wer administered DFP at doses of 0-1.5 mg/kg (sc). The animals were placed 60 min later into one of two motor activity chambers and tested for 30 min. Motor activity was measured using either a Doppler-based system or a commercial photocell device. Following measurement of motor activity in the Doppler system, body temperature (Tb) was measured and blood was then withdrawn by cardiac puncture and analyzed for serum cholinesterase activity (ChE). The remaining rats were retested 1 d after DFP administration in the photocell device. The results showed a significant influence of strain on the effects of DFP. Motor activity of LE rats was reduced by DFP at doses of 1.0 and 1.5 mg/kg, whereas the activity of F344 rats was reduced only at 1.5 mg/kg. The relative sensitivity of SD rats depended on the device used to measure motor activity. The SD rats resembled F344 rats in their response to DFP when motor activity was measured in the photocell device, and LE rats when motor activity was measured in the Doppler system. The Tb of F344 rats was unaffected by DFP, while the LE and SD rats became hypothermic at 1.5 mg/kg. The DFP-induced inhibition of serum ChE activity was significantly less in F344 rats. All three strains retested the day after DFP still showed significant decreases in motor activity. Overall, it appears that the F344 strain is relatively resistant to the behavioral and autonomic effects of DFP. This intraspecies variability should be considered in selecting appropriate experimental models for assessing the neurotoxicological hazards of cholinesterase-inhibiting pesticides. PMID- 8450558 TI - Hepatocyte cell proliferation in mice after inhalation exposure to unleaded gasoline vapor. AB - Chronic inhalation exposure to unleaded gasoline (UG) induced an increase in liver tumors in female but not male mice. Unleaded gasoline exhibits little, if any, genotoxic activity in vitro or in vivo in the female mouse liver, suggesting that other biological effects such as the induction of cell turnover or altered growth control may play a role in this carcinogenic process. To better understand the role of UG-induced hepatocyte proliferation with respect to the dose- and sex specific tumor response, male and female B6C3F1 mice were housed in 1-m3 single pass flow-through inhalation chambers and administered UG under exposure conditions that produced tumors in the chronic studies. Mice were exposed to targeted concentrations of 67, 292, or 2056 ppm PS-6 blend of UG vapor 6 h/d, 5 d/wk, for up to 13 wk. Liver weights were elevated significantly in male and female mice exposed to 2056 ppm UG at wk, 1, 3, 6, and 13. No elevation in liver specific serum enzymes was noted in treated animals, nor were there any significant histopathological changes in the liver, indicating a lack of overt hepatotoxicity. Hepatocyte proliferation, expressed as nuclear labeling index (Ll), was measured immunohistochemically after 5-bromo-2'-deoxyuridine administration via an osmotic minipump implanted three days before the animals were killed. A 6-to 10-fold increase in Ll compared to controls was observed in male and female mice exposed to 2056 ppm UG at wk 1, with a return to control levels at wk 3, 6, and 13. Mice exposed to 67 or 292 ppm UG did not show any increase in Ll. The mode by which an agent induces cell proliferation is an important consideration in mechanistic studies and the risk assessment process. These data indicate an early transient mitogenic stimulation of cell proliferation, rather than regeneration secondary to cytotoxicity, in the livers of UG-treated mice. The observed proliferative response after UG exposure in the male mouse in the absence of a tumorigenic response suggests that effects in addition to the early transient hepatocyte proliferation response are critical in understanding the sex-specific hepatocarcinogenic response of this complex mixture. PMID- 8450559 TI - Fumonisins--mycotoxins produced by Fusarium moniliforme. AB - Fumonisins are toxic metabolites of the fungus Fusarium moniliforme, which is a common contaminant of corn everywhere in the world. The fumonisins are carcinogenic in laboratory rats, and cause acute toxicity of domestic animals that mimics field cases of disease attributed to contamination of feed by F. moniliforme. These include both equine leukoencephalomalacia and porcine pulmonary edema. Fusarium moniliforme contamination of corn consumed by humans in certain areas of the world is associated with higher than average incidence of esophageal cancer, and fumonisins may be responsible. Analytical methods have been developed for fumonisins, but improvements are needed so that more accurate, less expensive, and more rapid assays of food and feedstuffs can be done. Fumonisins are structurally similar to sphingosine, and may exert their biological activity through their ability to block key enzymes (sphinganine- and sphingosine-N-acyltransferases) involved in sphingolipid biosynthesis. Much more research is needed to define the extent to which this mycotoxin adversely affects the food supply, and its involvement in animal and human diseases. PMID- 8450560 TI - Astrocytes: targets and mediators of chemical-induced CNS injury. AB - It is now well established that a reciprocal relationship exists between neurons and astrocytes, and that this association is vital for mutual differentiation, development, and functioning of both cell types. It had also become apparent that perturbations in astrocytic function may lead to deleterious consequences in juxtaposed neurons. It is therefore possible that neuronal damage induced by chemicals or neuropathic disease involves dissociation of astrocytic-neuronal interactions. The purpose of this review is to explore astrocytic-neuronal interactions, focusing on potential sites of neurotoxicant actions. In developing this thesis, we briefly examine the functional interactions between astrocytes and neurons, followed by specific examples of astrocyte-mediated neurotoxicity. PMID- 8450561 TI - Neurotrophin gene expression by cell lines derived from human gliomas. AB - The expression of neurotrophin (NGF, BDNF, and NT-3) mRNAs in 24 cell lines derived from human malignant gliomas was studied by Northern analysis. Widespread expression of neurotrophin genes was found with BDNF being the most abundantly expressed. Nearly all cell lines expressed BDNF, and about two-thirds of the cell lines expressed NGF and NT-3. Half of the cell lines analyzed expressed all three neurotrophins. Secretion of NGF into the medium of several cell lines could be detected by ELISA and a PC12 neurite outgrowth assay. Immuno- and bioactive NGF was isolated from conditioned medium of one cell line. No evidence of expression of the neurotrophin receptors trk and trkB by Northern analysis was found. Receptor crosslinking with radiolabeled cognate ligands failed to detect functional receptors in all but one cell line. In this cell line a receptor complex for BDNF was found that corresponded to truncated trkB receptors that lack the signal transducing tyrosine kinase domain. Neurotrophins did not stimulate mitosis of the glioma cultures. The findings suggest that production of neurotrophins by glioma cells is a general phenomenon, although neurotrophins made by gliomas lacking their receptors may not play an autocrine but rather a paracrine role. PMID- 8450562 TI - Insulin-like growth factor-I (IGF-I) production by astroglial cells: regulation and importance for epidermal growth factor-induced cell replication. AB - The insulin-like growth factors are postulated to play a role during brain development. Because they are believed to act in a paracrine/autocrine manner, the production of insulin-like growth factor-I (IGF-I) by cultured astroglial cells was examined. Quantities of IGF-I in conditioned media were determined by RIA after separation of IGFs from IGF-binding proteins by high-pressure liquid chromatography. Astrocytes from 1-day-old rats and the rat glioma cell line (C6) both secreted 7.5-kDa IGF-I. A peak of immunoreactivity with an apparent mol wt of 12,000 was additionally present in media conditioned by C6 cells. Exposure to epidermal growth factor (EGF) increased media content of immunoreactive IGF-I slightly (60%) in C6 cells but more than 2-fold in normal astrocytes. Fibroblast growth factor also increased the amount of IGF-I contained in media conditioned by normal astrocytes. To determine whether the secreted IGF-I was biologically active, media IGFs were immunoneutralized with a monoclonal antibody (Sm 1.25). In the presence of the antibody, EGF-stimulated astrocyte replication was blocked. These data indicate that IGF-I secretion by rodent astrocytes is stimulated by factors thought to be important for brain growth and development and that the IGFs are likely intimate participants in EGF-induced astrocyte growth. PMID- 8450563 TI - Identification of neuropeptide Y receptors in cultured astrocytes from neonatal rat brain. AB - Specific binding sites for neuropeptide Y could be demonstrated in primary cultures of astrocytes from neonatal rat brain. Neuropeptide Y binding was saturable, reversible, and temperature dependent as revealed by saturation studies and kinetic experiments. Scatchard analysis of equilibrium binding data indicated a single population of high-affinity binding sites with respective KD and Bmax values of 0.43 nM and 6.9 fmol/2.7 x 10(5) cells. Physiological responses induced by neuropeptide Y could be detected in a distinct subpopulation of cultured astrocytes on the basis of two criteria: 1) electrophysiological responses and 2) single cell measurements of changes in [Ca2+]i. In that fraction of cells responding (20-70%, varying among cultures from different preparations), brief application of neuropeptide Y led to a membrane potential depolarization, lasting several minutes. When the membrane was clamped close to the resting membrane potential using the whole-cell patch-clamp technique, neuropeptide Y induced an inward current with a similar time course as the neuropeptide Y induced membrane depolarization. As detected by single cell microfluorimetric (fura-2) measurements neuropeptide Y induced an increase of [Ca2+]i which was caused by the entry of extracellular Ca2+. Both the [Ca2+]i increase and the electrophysiological responses were unaffected by pretreatment of the astrocytes with pertussis toxin. PMID- 8450564 TI - Surface behavior of axolemma monolayers: physico-chemical characterization and use as supported planar membranes for cultured Schwann cells. AB - The axolemma membrane forms a stable and reproducible monomolecular layer at the air-aqueous interface. The major lipids and proteins are present in this monolayer in molar ratios similar to the original membrane. Acetylcholinesterase and Na-K-ATPase activities are preserved in the monolayer to levels of 64% and 25%, respectively. The total lipid fraction forms a homogeneously mixed phase. The presence of proteins in the monolayer introduces surface inhomogeneties. Among other features, this is revealed by the presence of two values of lateral pressure at which the monolayer shows partial or total collapse: a broad partial collapse at surface pressures between 13 to 30 mN/m and a sharp collapse point at 46 mN/m. The average molecular areas, the broad collapse point, and the variation of the surface potential per molecule suggest the relocation of protein components at surface pressures between 13 to 30 mN/m. The behavior is consistent with the extrusion and exposure of proteins toward the aqueous medium that depends on the lateral pressure. Schwann cells grown on coverslips coated with axolemma monolayers at 13 mN/m (beginning of the broad collapse) and 34 mN/m (above the broad collapse) recognize the difference in the surface organization of axolemma caused by the lateral pressure which affects their proliferation, morphology, and spatial pattern of organization. Our results show for the first time that response of Schwann cells depends on the intermolecular organization of the axolemma surface with which they interact. These results suggest that the local expression of putative surface molecules of axolemma that may mediate membrane recognition and the signalling of morphological and proliferative changes can be modulated by long range supramolecular properties. PMID- 8450565 TI - Cell volume regulation in cultured cerebellar granule neurons. AB - Cultured rat cerebellar granule neurons exposed to solutions of reduced osmolarity, responded initially by swelling followed by a regulatory volume decrease (RVD) which is completed within 15 min. Increasing external osmolarity lead to cell shrinking but no evidence of volume regulation was observed within 1 hr. Replacing Na+ by choline did not affect RVD whereas N-methyl-D-glucamine accelerated the volume recovery and K+ suppressed it completely. The blockade of RVD in high extracellular K+ was only observed when chloride and nitrate but not sulfate or gluconate were the accompanying anions. Replacing intracellular Cl-, by long incubations with gluconate, markedly inhibited RVD. Removal of extracellular Ca2+ or addition of dantrolene which blocks Ca2+ released from intracellular stores had no effect on RVD. Increasing extracellular taurine prevented RVD. These results indicate that membrane permeability to K+, Cl-, and taurine is increased by hyposmolarity and suggest the involvement of these molecules in RVD in granule neurons. PMID- 8450566 TI - Arachidonic acid lipoxygenation may mediate interleukin-1 stimulation of nerve growth factor secretion in astroglial cultures. AB - Interleukin-1 beta (IL-1) stimulates by about fivefold NGF secretion from rat neonatal cortical astrocytes in primary culture. We investigated the possible intracellular second messenger mechanisms involved in the IL-1 induced NGF secretion. Basal NGF secretion did not require extracellular Ca2+, whereas Ca2+ was necessary for the maximal NGF secretion stimulated by IL-1 (10 units/ml). The protein kinase C activator TPA stimulated by sixfold NGF secretion, but in this case, TPA acted synergistically with IL-1 to increase NGF secretion. Treatment of cells with the phospholipase A2 inhibitor mepacrine (30 microM) inhibited basal (by 50%) and IL-1 stimulated (by 80%) NGF secretion. Indomethacin, a cyclooxygenase inhibitor, produced a slight increase in basal NGF secretion at low concentrations, while PGE2 (10 microM) inhibited basal and IL-1 stimulated NGF secretion. In contrast, treatment of cells with nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, blocked in a concentration-dependent manner (IC50 = 10 microM) IL-1 stimulation of NGF secretion. The leukotriene LTB4 increased basal NGF secretion and this effect was not additive with IL-1 when both agents were added at saturating concentrations, indicating a common mechanism of action for these two agents. Thus, one possible mechanism by which IL-1 stimulates NGF secretion from astrocytes is by activation of the phospholipase A2-lipoxygenase pathway. PMID- 8450567 TI - Brain glutathione reductase induction increases early survival and decreases lipofuscin accumulation in aging frogs. AB - Brain catalase was continuously depleted throughout the life span starting with a large population of initially young and old frogs. Free radical-related parameters were measured in the brain tissue once per year after 2.5, 14.5, and 26.5 months of experimentation. Brain lipofuscin accumulation was observed after 14.5 and 26.5 months, and survival was continuously followed during 33 months. The age of the animal did not decrease endogenous antioxidants nor increase tissue peroxidation either in cross-sectional or longitudinal comparisons. Continuous catalase depletion similarly affected young and old animals, inducing glutathione reductase, tending to decrease oxidized glutathione/reduced glutathione (GSSG/GSH) ratio, decreasing lipofuscin accumulation in the brain, and increasing survival from 46% to 91% after 14.5 months. At 26.5 months of experimentation the loss of the glutathione reductase induction in catalase depleted animals was accompanied by the presence of higher lipofuscin deposits than in controls and was followed by a great increase in mortality rate. Even though the maximal life span (7 years) was the same in the control and treated animals which were already old (4.2 years) at the beginning of the experiment, the treated animals showed a strong reduction in the rates of early death. It is proposed that the maintenance of a high antioxidant/prooxidant balance in the vertebrate brain greatly increases the probability of the individual to reach the final segments of its species-specific life span. PMID- 8450568 TI - Long-term induction of c-jun mRNA and Jun protein in rabbit retinal ganglion cells following axotomy or colchicine treatment. AB - The expression of the c-jun, c-fos, and NGFI-A genes was studied in the rabbit retina after optic nerve crush (ONC) or an intravitreal injection of colchicine. By Northern blotting, the basal expression of c-fos and NGFI-A mRNAs were undetectable, whereas c-jun mRNA showed a low basal expression in sham-operated control retinas. Very few or no Jun- or Fos-immunoreactive nuclei were seen in control retinas. From 1 to 95 days after ONC a marked induction of JUN- but not FOS-immunoreactive neurons was seen in the ganglion cell layer peaking at 3 and 7 days. Jun-positive neurons also accumulated immunoreactive phosphorylated neurofilaments, indicating that they were ganglion cells. Northern blots demonstrated that retinal levels of c-jun mRNA, but not of c-fos or NGFI-A mRNAs, were increased 3 and 7 days after ONC. An intravitreal injection of colchicine also induced Jun-immunoreactivity within 24 hr in most of the neurons in the ganglion cell layer, but not in the inner nuclear and outer nuclear layers. The results indicate that axonal damage induces a specific pattern of IEG expression including a long-term induction of the c-jun gene in CNS neurons. PMID- 8450569 TI - Differences between alcoholics and spouses in their perceptions of family functioning. AB - The present study is an investigation of differences between alcoholics and significant others in their perceptions of the functioning of their families or households. A sample of 80 pairs of alcoholic patients (PTs) and their spouses or spouse equivalents (SOs) who were living together in the same household evaluated family functioning by completing the Family Assessment Device (FAD). Agreement between PTs and SOs was moderate on the Affective Responsiveness, Communication, Problem Solving, Roles, and General Functioning scales. However, there was little or no agreement on the Behavior Control and Affective Involvement scales. These results indicate that although PTs and SOs tended to agree about how well family members work together and share thoughts and feelings, they disagreed about how well boundary issues were dealt with in their families. Implications for treating alcoholic families are discussed. PMID- 8450570 TI - A developmental model of addictions, and its relationship to the twelve step program of alcoholics anonymous. AB - A shift in the psychoanalytic literature is seen to have taken place in the 1960s, when psychoanalysts abandoned the psychoanalysis of patients suffering from addictions. This was due to poor outcomes, and assertions such as Kohut's, that addiction was not analyzable. The author asserts that there is a similarity in the psychological part of all addictions, and that this is seen in his work with addicted patients, including psychoanalysis of addicted patients. Addiction is presented as a pathological solution to a fixation during separation individuation. This conceptualization helps to explain why such varying previous psychoanalytic formulations have been offered. The addictive solution to a fixation during separation-individuation is compared and contrasted to a similar fixation seen in patients suffering from borderline personality disorder and patients suffering from pathological narcissism. The developmental model presented clarifies how denial of addiction can be an interpersonal expression of an intrapsychic defense. PMID- 8450571 TI - Acupuncture: new perspectives in chemical dependency treatment. AB - The use of auricular acupuncture in treating acute drug withdrawal began in Hong Kong in 1972. Its practical application in the traditional drug treatment setting evolved at New York City's Lincoln Hospital during the 1970s, and over 250 acupuncture programs in diverse treatment settings have since been established world wide, based on the Lincoln protocol. Acupuncture treatment offers the client support during acute and postacute withdrawal through relief of classic symptoms. It has also been found useful as an entry point to treatment and/or recovery in such nontreatment settings as jails and shelters, and has particular efficacy in the treatment of resistant clients, and of prepartum and postpartum women. Though acceptance of the legitimacy of acupuncture by the chemical dependency community has been guarded, both research and outcome studies indicate that it holds promise as a complement to traditional substance abuse modalities. PMID- 8450572 TI - Dimensions of adolescent drug-avoidant attitude. AB - Attitudes toward drug and alcohol use and adolescent rates of substance use and abuse have consistently exhibited strong relationships. Yet, the authors maintain that the global construct of drug use attitude is amorphous and lacking in defined boundaries that allow for effective educational and treatment interventions. The purpose of the study was to examine the underlying dimensions of drug use attitudes that relate to substance use by adolescents. Six constitutive dimensions of drug use attitude were identified through factor analysis. These six dimensions are perceived peer attitude, alcohol-avoidant attitude, drug-avoidant attitude, performance attitude, image enhancement attitude, and perceived parental attitude. All six factors were found to correlate significantly with both drug experimentation and frequency of drug use. Two internally referenced factors (drug-and alcohol-avoidant attitudes) are discussed as outcomes of the attitude formation process. The four externally referenced attitude components (peer, parental, image enhancement, and performance attitudes) may influence the formation of internalized attitudes and suggest the need for interventions targeting peer and parental relations and youths' understanding and perception of how drug use impacts personal appearance and performance. PMID- 8450573 TI - Decline in intravenous drug use among treatment-seeking opiate users. AB - Opiate users seeking treatment during similar time periods in 1986 (n = 60) and 1988 (n = 82) did not differ significantly with regard to demographic factors, length of addiction, use of cocaine, history of alcohol problems, or indices of depression. In 1988, however, users reported significantly lower rates of current intravenous drug use than was reported in 1986: 39% in 1988, compared to 14% in 1986, reported not currently using IV (chi 2(1, N = 142) = 11.302, p < .001). For the combined periods, current IV users (n = 102) did not differ significantly from those who were not currently using IV (n = 40) with regard to demographic factors, size of habit, history of alcohol problems, or indices of depression. Current IV users had used opiates longer (mean 11.3 years versus 8.4 years; t(1, 65) = 2.20, p < .03), and there was a trend for cocaine use to be associated with current IV administration. For the smaller subset of those who survived waiting lists of between 1 to 4 months from the time of intake to program admission and physical examination (n = 81), 35% (6/17) of those who were not IV drug users at the time of clinic intake reported resuming or initiating IV drug use by the time of program admission. The validity of self-reports of not using IV at the time of program admission was assessed by comparison of self-report with findings of track marks on physical examination: inconsistencies were detected in 11% (1/9) of those whose self-reports indicated no current IV use. PMID- 8450574 TI - Psychopathology in alcohol- and cocaine-dependent patients: a comparison of findings from psychological testing. AB - Literature on cocaine-dependent patients studied through psychological testing remains limited, while there is much on assessment of alcoholics. This study replicated previous evaluation of cocaine-dependent patients, now compared with a group of alcoholics. Seventy-eight male and 21 female cocaine dependents and 70 male and 24 female alcoholics, hospitalized in a dual diagnosis program, were administered the MMPI, Millon Clinical Multiaxial Inventory-II (MCMI-II), Rorschach, Beck Depression Inventory, and Shipley Institute of Living Scale, after a 2-week stabilization period. Test data were statistically analyzed and compared along with demographic information. Cocaine-addicted subjects were younger, more often single and Afro-American, of lower socioeconomic status, less educated, and had slightly lower intellectual functioning and lesser family occurrence of addiction than alcoholics. Patients dependent on cocaine showed statistically more distress and psychopathology. Both groups demonstrated a high occurrence of personality disorders, but with different patterns of diagnoses. Implications for further research and treatment are discussed. PMID- 8450575 TI - The impact of gender on clinical characteristics and outcome in alcohol withdrawal. AB - Few studies have compared the social and clinical features of alcoholism for women and men, and none has focused on patients entering treatment for withdrawal. We investigated the role of gender by analyzing the data for 179 patients (34 women, 145 men) who underwent outpatient withdrawal. Our analysis focused on two questions: 1) How do women and men compare in terms of baseline social and clinical features? and 2) Do women and men have similar treatment outcomes in alcohol withdrawal? Baseline sociodemographic features revealed that women were more likely to be poor (90% vs. 71%, p = .03) but less likely to be uninsured (32% vs. 51%, p = .05), homeless (6% vs. 20%, p = .05), or have legal problems (29% vs. 54%, p = .02). Surprisingly, women and men reported a similar mean daily alcohol intake (240 g vs. 243 g). Women reported a shorter duration of alcohol abuse prior to entering treatment (16.1 y vs. 19.1 y). Although women experienced a higher treatment failure rate (53% vs. 43%), this difference is not significant. Our analysis highlights gender similarities and differences among patients entering treatment for withdrawal. We conclude that women and men have similar treatment outcomes in the management of alcohol withdrawal. PMID- 8450576 TI - Gender differences in cocaine use and treatment response. AB - Much of our understanding of treatment efficacy in drug abuse is based on male drug abusers. In order to determine if there are gender differences in baseline drug use and treatment response, we compared male and female cocaine abusers who participated in an outpatient randomized clinical trial (RCT) evaluating pharmacotherapies for cocaine abuse. Although females had more severe drug problems at intake, they were as successful as males in the RCT and more successful at 6-month follow-up. PMID- 8450577 TI - Cocaine-associated violence and relationship to route of administration. AB - The relationship between route of cocaine administration, that is, free base/crack smoking (FB), intravenous injection (IV), and nasal insufflation (NS) and level of violence was studied. The authors hypothesized that the route that produced the most intense effects (i.e., FB > IV > NS) would produce the highest level of violence. Over a 12-month period, 194 cocaine users were screened. After excluding polydrug users, 101 patients of both sexes participated in this study for the evaluation of expressions of violence. Evaluations were conducted by a structured questionnaire. The order of level of increased violence matched that of the most "intense" route of administration for some measures only. FB and IV use generally produced the same level of violence for most measurements. Both FB and IV routes produced more violence than NS. Violent actions requiring sustained activity (e.g., rape, burglary, and armed robbery) showed no relationship to route. The difference in levels in violence between males and females varied according to circumstance, not route of administration. PMID- 8450578 TI - Conducting HIV outreach and research among incarcerated drug abusers: a case study of ethical concerns and dilemmas. AB - This case involves the examination of an ethically problematic event that arose while we were conducting an outreach/early intervention research demonstration project targeted at women who exchange sex for drugs. Subjects were drug abusers- primarily crack-cocaine smokers--recruited by outreach workers on "the street" and in jail. Participants were offered counseling, HIV and syphilis screening, and risk-reduction education. A woman who was a jail inmate tested positive for HIV. In order to obtain medical and other assistance, she would have to reveal her serostatus to jail officials. This could result in isolation and the possibility of harm from others in the jail once the information about her circulated. The case highlights the problems inherent in HIV testing of incarcerated drug abusers, especially in low HIV seroprevalence areas. We recommend that a community empanel a committee composed of substance abuse treatment and medical professionals, civil rights advocates, criminal justice personnel, and ethicists to formulate humane and effective policy in light of its drug abuse and HIV problems and its resources. PMID- 8450579 TI - Methadone maintenance: predictors of outcome in a Canadian milieu. AB - This hypothesis-generating study attempts to identify patient characteristics predicting the successful outcome of methadone maintenance in the treatment of narcotic addiction. The sociodemographic characteristics as well as the general emotional health of 51 addicted individuals in Montreal were studied at entry into the program and are correlated with success one year after entry. The success of the Montreal program, defined as retention in the program and urine samples negative for opiates, is comparable to results reported from many North American clinics. A history of foster care before age 15 is the only characteristic significantly correlated with both retention and negative urines. Emotional health, previous treatment experiences, job status, and level of education do not correlate with success. All addicted individuals applying to a treatment program should therefore be accepted for a trial of treatment while further research on greater numbers of subjects may eventually identify predictors of successful outcome. PMID- 8450580 TI - Amino acid arterial concentration and muscle exchange during submaximal arm and leg exercise: the effect of dihydroxyacetone and pyruvate. AB - The mixture of dihydroxyacetone and pyruvate (DHAP) is an ergogenic aid that enhances muscle glucose extraction during prolonged aerobic exercise. In order to evaluate the effect of DHAP on muscle amino acid extraction during exercise, we measured arterial concentration and muscle exchange of amino acids in 18 untrained healthy male subjects (aged 20-30 years) performing dynamic arm (60% VO2 max, n = 9) or leg (70% VO2 max, n = 9) exercise to exhaustion with and without dietary supplementation of DHAP. The subjects consumed diets (146 kJ kg body weight-1 day-1) containing either 100 g polyglucose, Polycose (placebo, P) or DHAP (3:1, treatment) substituted for a portion of carbohydrate. The two diets were administered in a double-blind, random, crossover order for a 7-day period. At least 7 days separated the dietary protocols. Blood samples were drawn through radial artery and axillary or femoral vein catheters at rest, during exercise and at exhaustion. Arterial alanine concentration increased by 30% during arm exercise and by 50-60% during leg exercise. No other arterial amino acid concentration changed during exercise. At exhaustion, arterial alanine concentration decreased to pre-exercise levels with arm exercise but remained elevated after leg exercise. Despite changes in arterial concentrations of alanine with exercise, muscle exchange of alanine was not altered with exercise. Exercise did not alter muscle exchange of any amino acid. Arterial amino acid concentrations and muscle exchange of amino acids with exercise were similar with or without DHAP feeding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450581 TI - Training of the sprint start technique with biomechanical feedback. AB - The purpose of this study was to improve the individual starting technique of eight top junior sprinters using biomechanical feedback training. Three technical parameters (blocks spacing to the start line, knee angle of the front leg and proportion of body mass falling on the hands) were varied. The horizontal velocity at take-off and the time to 10 m were the criteria used to evaluate the effect of the technical changes. All of the parameters were measured simultaneously and the athletes were provided with feedback immediately after each attempt. Seven of eight sprinters showed a statistically significant improvement in starting performance after modifying the position of their blocks. The improvement in 10-m time and horizontal velocity at take-off did not correlate significantly. The power exerted during the starting action correlated significantly with the time to 10 m. Therefore, it was concluded that effective biomechanical feedback during the training of the sprint start should use power exerted as the principal criterion because horizontal velocity shows an intra individual optimal trend in improvement. PMID- 8450582 TI - Muscle mass of competitive male athletes. AB - The recent publication of the first validated equation for the estimation of muscle mass (MM) in men has made possible a comparison of MM in athletes from different sports. Limb girths and skinfold thicknesses were measured in 62 male athletes (aged 17-38 years) and 13 non-athletic males (aged 22-36 years). The MM (g) was calculated from the equation MM = S(0.0553 Gt2 + 0.0987 Gf2 + 0.0331 Gc2) 2445, where S is stature, Gt is the mid-thigh girth corrected for the front thigh skinfold thickness, Gc is the maximum calf girth corrected for the calf skinfold thickness and Gf is the uncorrected maximum forearm girth (all in cm). The athletes were classified as gymnasts (n = 10), basketball players (n = 10), body builders (n = 10), track and field power athletes (n = 12), track and field long sprinters (n = 10) or distance runners (n = 10). The MM means ranged from 38.4 kg for the distance runners to 58.7 kg for the body-builders. Both body-builders and basketball players had significantly greater MM than gymnasts, long sprinters, non-athletic males and distance runners (P < 0.01). Also, MM was greater in track and field power athletes than in distance runners (P < 0.05). The MM as a percentage of body mass (%MM) ranged from 56.5% in the non-athletic group to 65.1% in the body-builders; body-builders scored higher than basketball players (P < 0.05), distance runners (P < 0.01) and the non-athletic group (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450583 TI - Cardiovascular responses to leisure alpine skiing in habitually sedentary middle aged men. AB - In order to evaluate the cardiovascular responses to leisure alpine skiing of habitually sedentary and not particularly active adult men, a series of continuous recordings of heart rate (HR) was performed on 10 subjects aged 51.0 +/- 1.3 years (mean +/- S.E.) during a 6-day ski trip at an altitude of 1000-2485 m. From the very first day, the subjects spontaneously adopted a regimen of intense physical activity, since 17.9% of the HR values recorded on the ski runs were higher than 85% of the maximal theoretical HR [THRmax (beats min-1) = 220- age (years)], which represented 19.5% of the actual skiing time. On day 2, 10.7% of the HR values were higher than 85% THRmax, or 17.9% of actual skiing time. For the entire ski trip, the mean HR during skiing was approximately 126 beats min-1, which corresponds to 75% THRmax. At rest, HR in the morning did not change significantly from days 2 to 6 (from 80 +/- 4 to 75 +/- 4 beats min-1, P > 0.05), whereas HR in the evening correlated significantly with the duration of physical activity during the day (r = 0.487, P < 0.001). In all cases, HR at rest was significantly higher than before the trip, except in the evening of day 4, the day on which the subjects skied less because they were fatigued after skiing in the morning. Systolic blood pressure (SBP) at rest was always lower than the control established before the trip, whether taken in the morning or in the evening.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450585 TI - Ventilatory threshold and work efficiency during exercise on a cycle and rowing ergometer. AB - The purpose of this investigation was to determine the effects of increasing specific (rowing ergometer) and non-specific (cycle ergometer) workloads on parameters relating to the ventilatory threshold (Tvent) and work efficiency. When highly trained male rowers were tested using non-specific workloads, their %VO2 max values at Tvent were close to those characteristic of untrained subjects (74.6 +/- 6.2% VO2 max). However, when we tested the same subjects using specific workloads, we recorded values typical of highly trained athletes (85.0 +/- 4.4% VO2 max). For the non-specific exercise on the cycle ergometer, we recorded work efficiency values close to those of untrained subjects (22.8 +/- 2.1%); however, for the specific exercise on the rowing ergometer, we recorded much lower values (16.4 +/- 3.1%). Because of the results of the non-specific submaximal exercise tests, we suggest caution in the interpretation of physiological variables that may be sensitive to training status. The evaluation of Tvent and work efficiency as supplementary parameters during laboratory studies will enable researchers to ascertain the effectiveness of the training process used, as well as indicating the specificity of the loading apparatus. PMID- 8450584 TI - Effects of acute hypoxia on the VO2 max of trained and untrained subjects. AB - The purpose of this study was to compare the responses of highly trained (TR) and untrained (UT) subjects' maximal oxygen uptake (VO2 max) while breathing a hypoxic gas mixture. Two groups of healthy volunteers were recruited: (1) trained subjects (n = 8), VO2 max = 67.2 +/- 4.0 ml kg-1 min-1; (2) untrained subjects (n = 8), VO2 max = 45.4 +/- 5.5 ml kg-1 min-1. Both groups were administered maximal cycle ergometer tests under hypoxic (13% O2, 87% N2) and normoxic conditions (21% O2, 79% N2). A pulse oximeter (Ohmeda 3700) was used to estimate arterial haemoglobin saturation (SpO2). The trained group had lower values for SpO2 at maximal exercise (TR = 67.0 +/- 7.1%; UT = 77.5 +/- 9.0%) and greater reductions in VO2 max while breathing the hypoxic gas mixture was linearly correlated with the subjects' normoxic VO2 max (ml kg-1 min-1: r = -0.91). These results indicate that highly trained subjects experience greater percent decrements in SpO2 and VO2 max while breathing a moderately hypoxic gas mixture compared to untrained subjects, and may explain some of the variable decrease observed when VO2 max is measured at simulated altitude. PMID- 8450586 TI - Rate of accumulation of blood lactate during graded exercise as a predictor of 'anaerobic threshold'. AB - The subject group comprised 35 endurance-trained males: 11 young adults, 11 seniors and a control group of 13 young adults. A graded submaximal exercise test on a treadmill was performed by 22 of the subjects. The exponential function [La ] = a.ebx + c (where x = running velocity) showed a high degree of correlation with the experimental results (mean r = 0.997) and had randomly distributed residuals. Twenty-two subjects performed a series of running sessions at constant speed to establish the highest working intensities that could be endured without an increase in blood lactate (BLa) - the maximal steady-state workload (MSSW). The observed velocities of MSSW were related to the BLa vs velocity curves from the graded test. The graded submaximal exercise tests yielded mean derivatives from the BLa vs velocity relationship curves equal to 0.089 and 0.083 mM per m.min-1 for the young and senior groups, respectively. The derivatives had moderate inter-individual variations. In reversing the procedure, MSSW was estimated for all of the subjects using a common slope of 0.086. Only small individual variations were found between observed and estimated MSSW. The mean BLa value f (x), calculated using exponential functions where x = individual observed MSSW, was 3.0 mM. Thus, for endurance-trained athletes, a BLa accumulation rate of 0.086 mM per m.min-1 or, alternatively, a fixed BLa concentration of 3 mM, is recommended as a predictor of MSSW when analysing the BLa-velocity profiles from a graded submaximal test. PMID- 8450587 TI - Physiological characteristics related to endurance running performance in female distance runners. AB - The purpose of the present study was to determine the relationships between running velocity (v) in a 3000-m race and various physiological parameters. The parameters measured among 57 female distance runners during a treadmill running test were v at the lactate threshold (v-Tlac), oxygen uptake (VO2) at the lactate threshold (VO2 at Tlac), v at the onset of blood lactate accumulation (v-OBLA), VO2 at OBLA, running economy (steady-state VO2 at a standard v of 4 m s-1), maximal oxygen uptake (VO2 max) and v at VO2 max (v-VO2 max). The v-OBLA was the blood lactate variable with the strongest correlation with v in a 3000-m race (r = 0.78, P < 0.001). The second strongest correlation was with v-Tlac (r = 0.77, P < 0.001). Although v-VO2 max was strongly correlated with v over 3000 m (r = 0.75, P < 0.001), further analysis by stepwise multiple regression indicated that a combination of v-OBLA, VO2 at Tlac and v-Tlac could account for 73.2% of the variability in v over 3000 m, whereas v-OBLA on its own explained 61.5%. Blood lactate variables can account for a reasonably large part of the variance in v over 3000 m. Also, v-VO2 max can be used as a non-invasive predictor of distance running performance. PMID- 8450588 TI - Biomechanical study of the final push-pull in archery. AB - The purpose of this study was to analyse archery performance among eight archers of different abilities by means of displacement pull-hand measurements during the final push-pull phase of the shoot. The archers showed an irregular displacement negatively related to their technical level. Displacement signal analysis showed high power levels in both the 0-5 Hz and 8-12 Hz ranges. The latter peak corresponds to electromyographic tremor observed during a prolonged push-pull effort. The results are discussed in relation to some potentially helpful training procedures such as biofeedback and strength conditioning. PMID- 8450589 TI - A comparative study of the aerobic fitness of 421 healthy adult males in Singapore. AB - The maximum oxygen consumption (VO2 max) of 421 healthy adult males from three ethnic groups (Chinese, Malay and Indian), aged 25-54 years, was assessed from direct analyses of their expired respiratory gases during all-out runs on a treadmill as a measure of aerobic fitness. The subjects were divided into three age groups: group 1, 25-34 years; group 2, 35-44 years; group 3, 45-54 years. Each group was further subdivided into non-exercisers (NE), non-regular exercisers (NRE) and regular exercisers (RE). Consistently within each age group, regular exercisers produced significantly higher VO2 max values compared to non regular exercisers and non-exercisers. They also met the VO2 max requirements for heavy physical work and compared favourably with the standards of the National Physical Fitness Award of Singapore and Cooper's aerobic fitness classification standards based on North American males. Non-regular exercisers and non exercisers only met the VO2 max requirements for moderate physical work and compared poorly in both of the aerobic fitness standards. PMID- 8450590 TI - The effects of periodized velocity-specific resistance training on maximal and sustained force production in women. AB - The purpose of this study was to assess the effects of slow, fast or periodized slow and fast resistance training on voluntary, maximal and sustained force production. Altogether, 34 active females were pre-tested for maximal force production (MXF) and 20-repetition mean force production (MNF) at 1.05 and 3.14 rad s-1 (60 and 180 deg s-1). They were then randomly placed into one of four groups: group S trained for 8 weeks at 1.05 rad s-1, group F trained for 8 weeks at 3.14 rad s-1, group P trained for 5 weeks at 1.05 rad s-1 and 3 weeks at 3.14 rad s-1, while group C acted as the controls. Groups S, F and P demonstrated significant increases in MXF and MNF at 1.05 and 3.14 rad s-1. The increases in MXF were similar between the trained groups, whereas groups S and P demonstrated significantly greater increases in MNF than group F at 1.05 rad s-1 and group P exhibited significantly greater increases in MNF than group S at 3.14 rad s-1. These results suggest that, regardless of training velocity, similar increases in MXF are produced at 1.05 and 3.14 rad s-1, whereas periodized slow and fast resistance training may produce greater increases in MNF than slow or fast training alone. PMID- 8450592 TI - AUA 88th annual meeting. San Antonio, Texas, May 15-20, 1993. Program and abstracts. PMID- 8450591 TI - Prediction and measurement of frame size in young adult males. AB - The assessment of frame size is a problematic and ambiguous area. The purpose of this study was to assess the level of agreement between various techniques of assessing frame size in a group of 27 healthy and active men aged 18-24 years, and also to assess which anthropometric variables were best associated with a measure of actual frame size (AFS) which is proposed in this study. Actual frame size was measured by the summation of a series of bone breadths, lengths and depths on a sub-sample of 17 men. The results of the study revealed substantial discordance between methods of assessing frame size. The variables which correlated most highly with AFS (P < 0.01) were body mass, ankle breadth, hand length and chest breadth, respectively. These variables were also positively correlated (P < 0.01) with fat-free mass (FFM), with no significant correlation with fat mass in either case. Of the various documented methods used to assess frame size, the 'HAT' technique, which incorporates biacromial and bitrochanteric breadths, was more highly correlated with AFS than both elbow breadth (currently used in height-weight insurance tables) and the height/wrist circumference index. The latter measure was not highly correlated with AFS, body mass and FFM in this study. It was concluded that ankle breadth and hand length may be better predictors of frame size in young men than other bone dimensions. In addition, the results of this preliminary investigation have substantiated the potential viability of an AFS model. Future research using this technique is recommended to determine true indicators of frame size in a larger and more heterogeneous population. PMID- 8450593 TI - Exponential correction of QT interval to minimize the effect of the heart rate in children. AB - The exponential correction of the QT interval (eQTc) was studied using 12,543 resting electrocardiograms obtained in children (first and seventh graders) who were screened for heart disease in Kagoshima City. The values of eQTc to minimize the effect of the RR interval were estimated using following exponential model, eQTc = (QT interval)/(RR interval)--k. The parameter k = 0.31 was found to be the most useful exponent. The distribution of eQTc values showed a hiatus or break at probability points near p < 0.001 or p < 0.0005. Tentative criteria for an abnormally long eQTc were selected using these points and the following convenient data: 0.430 and 0.435 for the male and female first graders, and 0.440 and 0.445 for the male and female seventh graders, increased by 0.005, respectively. Abnormal values must ultimately be selected using data on patients with the long QT syndrome; however, our findings suggest that the exponential correction of the QT interval may be useful in large-scale screening programs for detecting a QT prolongation in young school children. PMID- 8450594 TI - Spatial orientation of the vectorcardiogram in patients with myocardial infarction. AB - We studied the rotation angles on the each of 3 axes and the planarity and roundness of QRS loop when its plane was laid close to horizontal in 4 groups of patients. Thirty five had anterior myocardial infarction, 34 inferior infarction, 15 non Q wave inferior infarction, and 34 were normal subjects. The rotation angles of the QRS loop were significantly different from the controls, on the Y and Z axes in the anterior infarction group, on the Z axis in the inferior infarction group and on the X axis in the non Q wave inferior infarction group (p < 0.01). The planarity index in the inferior infarction group was significantly higher (p < 0.01) than in other groups. The significantly smallest value of the roundness index was noted in the anterior infarction group (p < 0.01). Significant features of the early segmental planarity indexes were shown in the non Q and Q wave inferior infarction groups (p < 0.01). We conclude that the rotation angles and the planarity and roundness indexes are characteristic parameters for the infarct group and may be useful for diagnosing myocardial infarction, which is difficult with electrocardiography and vectorcardiography. PMID- 8450595 TI - Clinical characteristics of patients with spontaneous remission of variant angina. AB - To determine the factors influencing the spontaneous remission of variant angina, clinical characteristics were examined in 75 Japanese patients with variant angina. Spontaneous remission was defined as an absence of angina at rest for at least 3 months after withdrawal of treatment with calcium antagonists. This remission occurred in 12 patients (16%) (remission group), while angina persisted despite treatment with calcium antagonists and nitrates in 33 patients (44%) (persistent angina group). The remaining 30 patients (40%) were angina-free under treatment with calcium antagonists and/or nitrates (angina-free on treatment group). The prevalence of significant coronary artery stenosis (> 75%) was significantly higher in the remission group than in the persistent angina group (44% vs 7%, p < 0.05). The prevalence of cessation of smoking was significantly higher in the remission group than in the persistent angina group (92% vs 39%, p < 0.01). Age, gender, other coronary risk factors, disease activity of variant angina and site of myocardial ischemia during anginal attacks were not statistically different among the 3 groups. There data indicate that remission of variant angina occurs more frequently in patients with than in those without significant coronary artery stenosis and that cessation of smoking is an important factor for remission of variant angina. PMID- 8450596 TI - The body surface QRST isointegral maps in infants with right ventricular overload. AB - Electrocardiographic criteria for right ventricular (RV) hypertrophy in infants generally exhibit low sensitivity in terms of diagnostic accuracy. We studied the QRST isointegral map (QRST-Imap) of body surface potential distribution for the diagnosis of RV overload in patients less than 2 years old. Patients with atrial septal defect (ASD), pulmonary stenosis (PS) and tetralogy of Fallot (TOF) were examined (RV overload group) and the findings of their QRST-Imaps were compared to those of age-matched healthy infants (NOR). QRST-Imaps in RV overload showed abnormal findings, with two maxima or a rightward shift of the maximum with increased amplitude, in contrast to one maximum at the left anterior chest with a single dipole pattern in the NOR group. ASD patients had two maxima with a decreased integral value between them. In PS, two maxima were also observed, with increased integral values of the right maximum as the RV systolic pressure was elevated. TOF patients showed a single maximum shifted to the anterior median line with increased amplitude. These results indicate that the findings of QRST Imaps are of value in detecting the presence and pattern of RV overload in infants. PMID- 8450597 TI - Effects of rHuEPO therapy on exercise capacity in hemodialysis patients with coronary artery disease. AB - We investigated the effects of recombinant human erythropoietin (rHuEPO) therapy on exercise capacity by symptom-limited maximal treadmill exercise testing in 9 patients with coronary artery disease who were receiving maintenance hemodialysis. The initial hemoglobin concentration of 7.9 +/- 0.7 g/dl, (mean +/- S.D.) rose to 10.4 +/- 1.1 g/dl, (p < 0.01) after three months of rHuEPO therapy. The partial correction of renal anemia resulted in a significant increase in exercise duration (from 278 +/- 84 sec to 384 +/- 74 sec, p < 0.01) and maximum pressure-rate product (from 228.3 +/- 50.3 mmHg.bpm/10(2) to 262.8 +/- 40.4 mmHg.bpm/10(2), p < 0.01). The maximum exercise-induced ST segment depression significantly decreased after treatment (from 1.3 +/- 0.5 mm to 0.5 +/- 0.5 mm, p < 0.05). These results suggest that the improvement in maximum coronary oxygen supply exceeded the increased maximum myocardial oxygen requirements after the partial correction of renal anemia by rHuEPO therapy in hemodialysis patients with coronary artery disease. PMID- 8450598 TI - Iodine 125-phenylpentadecanoic acid and its beta-methyl substitute metabolism in cultured mouse embryonal myocytes--iodine-labelled fatty acids as tracers of myocardial high energy phosphate. AB - Iodine-labelled fatty acids have been proposed as new tracers of cardiac metabolisms. However, it is not clear how these tracers would reflect the intracellular metabolism. Therefore, we measured the uptake and release of iodine 125-labelled phenylpentadecanoic acid (IPPA), its beta-methyl substitute (BMIPP) and 201Tl in cultured myocytes of mouse embryos, and compared these values to intracellular adenosine triphosphate (ATP) content after metabolic inhibitions of oxidative phosphorylation by sodium cyanide (CN), glycolysis by 2-deoxyglucose (2 DG) or fatty acid beta-oxidation by lactate. The uptake and release of BMIPP was not changed by any inhibitors suggesting BMIPP would not be metabolized in the myocytes. The uptake of IPPA was significantly reduced by 2DG and 60-80% of IPPA was metabolized to hydrophilic catabolites. The correlation of BMIPP and IPPA uptake to intracellular ATP content were high (r = 0.89, p < 0.05; r = 0.86, p < 0.1), but there was poor correlation of 201Tl to ATP values (r = 0.53, n.s.). These results suggested that iodine-labelled fatty acids could be used as better tracers of myocardial metabolism than 201Tl. PMID- 8450599 TI - Effect of regression of cardiac hypertrophy on ischemic myocardial damage in spontaneously hypertensive rats. AB - Effects of reduction of blood pressure and regression of left ventricular hypertrophy following hydralazine and captopril therapy on ischemic cardiac function and myocardial metabolism were studied in spontaneously hypertensive rats (SHR). Hydralazine (1.5 or 3 mg/kg/day) and captopril (50 or 100 mg/kg/day) were administered to SHR from 19 to 26 weeks of age. Both hydralazine and captopril significantly decreased arterial blood pressure in SHR, but only captopril significantly reduced left ventricular weight. The percentage of V3 myosin isozyme significantly decreased in captopril-treated SHR compared to hydralazine-treated SHR. At the end of long-term treatment, hearts were removed and perfused for 15 min by the working heart technique, and then global ischemia was induced for 30 min. The ischemic heart was reperfused for 30 min. In hydralazine-treated SHR and captopril-treated SHR, the pressure-rate product and extent of recovery of the coronary flow during reperfusion following 30 min of ischemia were higher than those in control SHR, but this difference was significant only in captopril-treated SHR. Hydralazine and captopril treatment improved the restoration of the levels of ATP, creatine phosphate, total adenine nucleotide and energy charge potential in SHR after reperfusion following 30 min of ischemia, but only captopril had a significant effect. In conclusion, regression of left ventricular hypertrophy is more important than lowering of blood pressure in order to improve the ischemic myocardial damage. PMID- 8450600 TI - Hemodynamic effects of milrinone in patients with congestive heart failure--short and long-term follow up studies. AB - The hemodynamic effects of milrinone (Mil) were studied in 11 patients with congestive heart failure (CHF) and New York Heart Association (NYHA) functional class II-IV before and after a 2-week treatment. The plasma concentration of Mil was also determined and its pharmacokinetics analyzed. The effect of a placebo was examined before the initiation of the treatment. At the onset, the hemodynamic effects of a single oral dose of Mil (7.5 mg) were evaluated. Mil increased the cardiac index significantly (p < 0.05) 4 h after administrations from 2.3 +/- 0.4 to 2.9 +/- 0.6 L/min/m2. The pulmonary capillary wedge pressure (PCW) was lowered significantly by Mil (p < 0.05) between 0.5 and 4 h after administration. After a 2-week treatment, the baseline PCW dropped (p < 0.05) and the NYHA functional class improved in 10 patients. One patient remained in the same class (II). The improved NYHA class was maintained in 6 patients tested after a mean interval of 16 +/- 3 months. Single oral administration of Mil (7.5 mg) induced hemodynamic improvements after 2-week treatment and the drug also induced similar improvements even after the chronic oral therapy with Mil for 16 +/- 3 months. Pharmacokinetic analysis showed a significant increase in the area under the curve after 2 weeks of treatment. We conclude that Mil decreases the PCW and probably increases the cardiac index and thus improves the symptoms and NYHA functional class in patients with CHF. PMID- 8450601 TI - [Rearrangements of immunoglobulin light chain and heavy chain constant region genes in B-cell malignancies]. AB - We analyzed immunoglobulin (Ig) gene rearrangements in 69 patients with B-cell malignancies by Southern hybridization. We used 5 probes which covered JH 5'S mu and S gamma 3 loci of the Ig heavy (IgH) chain gene, and C kappa and kappa de loci of the Ig light (IgL) chain kappa gene, respectively. DNA rearrangements were observed in 68 out of the 69 patients using the JH probe. In 97% (33/34) of patients with non-Hodgkin's lymphoma (NHL), 100% (5/5) of chronic lymphocytic leukemia (CLL), 42% (10/24) of non-T cell acute lymphoblastic leukemia (non-T ALL), and in 0% (0/4) of chronic myelogenous leukemia lymphoid crisis (CML-LBC), the rearrangements were detected by C kappa and/or kappa de probes. Furthermore, the genotype of the light chain was defined by rearrangement patterns of these 2 probes. The by using the 5'S mu-probe, class switch recombinations were detected in 76% (25/33) of NHL, 20% (1/5) of CLL, 17% (4/24) of non-T ALL, and in 0% (0/4) of CML-LBC. Among them, 1 case of IgM NHL and 3 cases of double bearer NHL had rearranged on both IgH alleles by the constant region. The results of this study indicate that genotypes correspond well to phenotypes of B-cell malignancies and that the determination of genotype will be useful for making an exact diagnosis of B-cell malignancies. PMID- 8450602 TI - [Analysis of cytoplasmic antigens in acute leukemia by flow cytometry]. AB - The expression of cytoplasmic antigens in 77 cases of acute leukemia were analyzed by flow cytometry using the following monoclonal antibodies: CD3, CD22, anti-myeloperoxidase (MPO-7) and anti-mu-heavy chain. CD22 antigen was detected in the cytoplasm of all non-T-ALL patients excluding one not-tested patient. In two patients with unclassified ALL, surface CD22 antigen was not expressed but cytoplasmic CD22 antigen was strongly expressed. Three out of 9 patients with common ALL were cytoplasmic mu-heavy chain-positive, so these patients were diagnosed as Pre-B ALL. In four out of 8 patients with T-ALL, CD3 antigen was not expressed on the cell surface membrane. However all of T-ALL patients excluding one non-tested patient were cytoplasmic CD3-positive. The cytoplasmic expression of myeloperoxidase antigen was detected in twenty out of 21 patients with acute non-lymphoblastic leukemia (ANLL). One megakaryocytic leukemia patient was MPO negative. In two ANLL patients, the percentage of MPO for conventional cytochemical staining was undetectable or low, but MPO antigens were positive (77% and 70%) for flow cytometric analysis. All of 46 non-T ALL patients were cytoplasmic MPO-negative, however 4 out of 10 T-ALL patients were cytoplasmic MPO positive. The study proved that the analysis of cytoplasmic CD3, CD22, mu-chain and MPO antigens were very useful to define the cell lineage of leukemia and to classify ALL and ANLL. It is necessary to study further whether the expression of MPO in the cytoplasm of T-ALL was non-specific reaction or whether MPO precursors are expressed in the cytoplasm of T-ALL. PMID- 8450603 TI - [Pathogenic relevance of platelet-associated autoantibodies in chronic ITP- studies before and after splenectomy in three patients with chronic ITP by direct immunoprecipitation procedure]. AB - This study was designed to investigate the pathogenic relevance of platelet associated autoantibodies in chronic ITP, since the titer of platelet-associated autoantibodies does not appear to correlate with the severity of the disease. Employing a direct immunoprecipitation procedure, we examined platelets from three ITP patients with platelet-associated autoantibodies against GPIIb-IIIa and an unidentified 56 kD protein before and after splenectomy. In two patients, platelet-associated autoantibodies disappeared after splenectomy, and these two patients attained complete remission. In one patient, however, the amount of platelet-associated autoantibodies did not decrease after splenectomy. Although this patient's platelet count transiently increased to 500 x 10(3)/microliters after splenectomy, it decreased to 55 x 10(3)/microliters within a short time. These findings suggest that platelet-associated autoantibodies play a key role in platelet destruction in chronic ITP. PMID- 8450604 TI - [Human parvovirus B19 infection in patients with hematologic disorders on chemotherapy]. AB - We described two cases having erythroid hypoplasia and pancytopenia, respectively, caused by human parvovirus B19 (PVB19) infection on chemotherapy. The first patient was a seven-year-old boy with Non-Hodgkin's lymphoma. He has obtained complete remission with LSA2L2 protocol, but, immediately after this remission, he suddenly developed high fever, erythema on cheeks and severe anemia without reticulocytes. We concluded that the cause of anemia and other symptoms were due to PVB19 infection because PVB19 DNA in his serum was detected by dot blot hybridization and polymerase chain reaction, although specific antibodies to PVB19 remained absent. He received gamma-globulin intravenously (200mg/kg/day for 5 days). The fever and erythema were improved promptly, but viremia and anemia lasted a few weeks and the specific antibodies to PVB19 were negative for about two months thereafter. The second patient was a nine-year-old boy with common ALL in remission. Pancytopenia suddenly occurred under maintenance therapy. Because IgM to PVB19 was detected in his serum, the patient was diagnosed to have temporary pancytopenia due to PVB19 infection. In conclusion, it is important to confirm specific antibodies and PVB19 DNA in serum when anemia or pancytopenia of unknown cause occurs in immunocompromised patients receiving chemotherapy. PMID- 8450605 TI - [Cyclosporine-induced graft-versus-host disease in a syngeneic bone marrow transplantation]. AB - A 33-year-old woman with AML (M4) resistant to chemotherapy received syngeneic marrow graft from her identical twin following high dose busulfan and etoposide. However, the relapse was confirmed on the 60th day after the procedure. Since she failed to achieve remission despite intensive chemotherapy, a second BMT from the same donor was performed following total body irradiation and high dose etoposide on the 126th day after the initial BMT. At this time, cyclosporine (1 mg/kg/day) was administered to induce graft-versus-host disease (GVHD). Skin rash appeared on the 18th day after the 2nd BMT, and biopsy from the rash on the 23rd day showed a typical picture of cutaneous GVHD (grade 2) and there was no evidence of viral infection. On the 36th day after the 2nd BMT, the patient died of veno occlusive disease. Although graft-versus-leukemia effect in this patient could not be evaluated because of early death, the induction of GVHD with cyclosporine might be effective to reduce the relapse rate after syngeneic or autologous BMT. Further studies are required to confirm this effect. PMID- 8450606 TI - [Reinfusion of concentrated autogenous ascitic fluid in a patient with selective IgA deficiency]. AB - A 47 year-old man with selective IgA deficiency (SIgAD) consulted us in November 1981, with complaints of leg edema and common cold-like symptoms and was diagnosed as SIgAD based on data of his serum protein (IgG 2,160 mg/dl, IgM 65 mg/dl, no detectable IgA). Later in July 1989, he was admitted with edema and ascites. Laboratory examinations showed; total protein 4.6 g/dl, albumin 1.26 g/dl, IgG 2,375 mg/dl, IgM 38 mg/dl, no detectable IgA. C3 22 mg/dl, C4 6 mg/dl, antinuclear antibody 80X, anti dsDNA antibody 4.5 U/ml, anti IgA antibody 258%, and lymphocytopenia. Co-culture of lymphocytes from the patient and normal subject revealed deficiency of IgA synthesis in his B cell populations. Systemic lupus erythematosus was suggested based on the findings of skin biopsy, renal damage, oral ulcer, decreased complements, autoantibody and lymphocytopenia. We could not give him conventional products of albumin and frozen plasma because he had anti IgA antibody. Instead, we administered concentrated autogenous ascitic fluid and prednisolone. His ascitic fluid disappeared and complements and albumin in his serum normalized. He has continued in good condition and is being treated as an outpatient. PMID- 8450607 TI - [Intermediate lymphocytic lymphoma with multiple lymphomatous polyposis of the gastrointestinal tract]. AB - We report a case of intermediate lymphocytic lymphoma (ILL) with multiple lymphomatous polyposis. A 56-year-old man presented with general fatigue and bloody stool. Physical examination showed cervical and axillary lymphadenopathy, bilateral tonsillar hypertrophy, and moderate splenomegaly. Leukocyte count was 9,570/microliters with 11% abnormal cells, infiltration of which was observed in the bone marrow too. Examinations of the gastrointestinal tract revealed diffuse small polypoid lesions throughout the stomach and the entire large bowel. The biopsied specimens from both the stomach and large bowel showed diffuse infiltration of medium-sized lymphoid cells in the submucosa and the lamina propria. Lymph node biopsies showed ILL (mantle zone lymphoma). The phenotype of lymphoma cells was CD5 (+) CD10 (-) CD19 (+) CD20 (+) CD21 (+), and sIg mu delta lambda. The patient was initially given the multiple agent chemotherapy, which did not improve the peripheral blood findings and was switched to the regimen that comprised of etoposide and prednisolone. The patient's lymphoma is well controlled by this regimen 35 months after diagnosis. PMID- 8450608 TI - [Two cases of acute leukemia with t(6;9) (p23;q34)]. AB - Two cases of acute leukemia with a t (6;9) (p23;34) chromosome abnormality are reported. The first case was a 34-year-old female who was hospitalized in October 1989. A diagnosis of FAB-M1 was made. Chromosomal analysis of the bone marrow cells showed a 46, XX, t (6;9) (p23;q34). Complete remission was achieved after two courses of BHAC-DMP therapy. In September 1991, at the time of relapse, chromosomal analysis revealed two abnormal clones consisting of a 46, XX, t (6;9) (p23;q34), -12, -17, +der (12) t (12;17) (p11.2;q11.2) with a residual normal clone. She died in February 1992. The second case was a 42-year-old male who was hospitalized in January 1990. He was diagnosed as having RAEB. Chromosomal analysis of the bone marrow cells showed 46, XY, t (6;9) (p23;q34). Three months later, the disease progressed to acute leukemia accompanied by leg ulceration with leukemic cell infiltration. Small-dose ara-C therapy was given, but with no effect. After two subsequent courses of therapy with low-dose etoposide, complete remission was achieved. Four months later, relapse occurred, and the patient died of sepsis in February 1991. In the literature, 31 cases of myeloproliferative disorders with t (6;9) have been reported. PMID- 8450609 TI - [Four cases of CD7-positive acute myeloid leukemia]. AB - This report describes 4 cases of T-cell-associated CD7-positive acute myeloid leukemia (AML). Myelo-peroxidase staining of blasts was negative in 2 cases but became positive during their courses. In all cases, the myeloid determinants CD13 and/or CD33 were associated with CD7 expression. Other B-lymphoid (CD10, CD19) or T-lymphoid (CD2) markers were negative. In three cases, dual fluorescence analyses showed co-expression of CD7 and CD13 (CD33). Clinically, compared with CD7+AML, these CD7+AML patients presented higher leukocyte and blast counts in peripheral blood. All patients achieved complete remission with chemotherapeutic regimens for AML, but 3 relapsed within a short time. Systemic lymphadenopathy was found in 2 cases, and interestingly, the surface markers of the lymph-node in one case were CD7+CD33-. These cases of CD7+AML may represent a distinct subgroup that arises from particular, less different myeloid precursors, and may have poor prognosis. PMID- 8450610 TI - [Testicular relapse, with Ph-positive chromosome after bone marrow transplantation for acute lymphocytic leukemia]. AB - A 25-year-old man with acute lymphocytic leukemia (ALL) had received bone marrow transplantation (BMT). Testicular relapse occurred 6 months after BMT as the first relapse, and couple of weeks later, bone marrow relapse developed. At that time, karyotypic analysis showed Ph-chromosome which was not observed before the first remission and DNA analysis revealed rearrangements of minor BCR, IgL, IgH, TCR and TCR genes. Testicular relapse often develops in ALL of children after BMT. However, some reports, including this report, indicate that testicular relapse following BMT can also occur in adults, so that the incidence of testicular relapse could be reduced either by total body irradiation (TBI) or testicular irradiation before transplantation. Incidence of Ph-positive chromosome following BMT is a key to illuminate the mechanism of the Philadelphia chromosome. Rearrangements of Ig and TCR gene can be considered as an abnormal gene rearrangement occurring at an early stage of B cell proliferation. PMID- 8450611 TI - [A case of dermatomyositis complicated by thrombotic thrombocytopenic purpura (TTP) which responded to combination of gamma globulin and vincristine--clinical analysis on TTP cases in the Japanese literatures]. AB - A rare case of dermatomyositis and thrombotic thrombocytopenic purpura (TTP), which responded dramatically to high-dose gamma globulin and vincristine is presented. A 42-year old man was admitted for evaluation of polymyalgia and skin change of the face and fingers. Findings of muscle biopsy was consistent with the diagnosis of dermatomyositis. During the course of his hospital stay, he had diffuse purpura, hematuria, high fever, and his consciousness became disturbed. The hemoglobin level and the platelet count decreased. Based on microangiopathic hemolytic anemia, thrombocytopenia and neurological abnormality, a clinical diagnosis of TTP was made. Therapy included high-dose gamma globulin, vincristine, corticosteroids and dextran. One week later, his consciousness became clear, hematological findings improved, and prolonged remission has been maintained for more than 19 months at the time of this report. This case suggests that gamma globulin and vincristine are effective in some with TTP cases. Case reports that have appeared in the Japanese literature are summarized and reviewed in terms of treatment. PMID- 8450612 TI - [Evaluation of the benefits of sodium 2-mercaptoethane sulfonate (MESNA) therapy for children undergoing high-dose chemotherapy]. AB - Preventive effects of hemorrhagic cystitis by the use of sodium 2-mercaptoethane sulfonate (MESNA) was evaluated in 40 children undergoing peripheral blood stem cell autografts (PBSCT) after marrow-ablative chemotherapy which included high dose cyclophosphamide (CY, 50mg/kg x 2). Fifteen patients received MESNA (group A) and 25 did not (group B), and all received concomitant hyperhydration (3,000ml/m2/day). No renal dysfunction or toxicity attributed to the use of MESNA was observed in either group of patients. Transient hemorrhagic cystitis developed in one of the 15 group A (6.7%) and 3 of 25 (12.0%) group B patients but there was no statistical significance. Although the results may suggest that MESNA is a controversial agent in preventing hemorrhagic cystitis caused by CY when hyperhydration protocol is used, further observation with a larger number of patients is required to establish a firm conclusion. PMID- 8450613 TI - [Detection of granulocyte-macrophage colony-stimulating factor activity in the supernatant of the cultured leukemic cells of adult T-cell leukemia with eosinophilia]. AB - An adult T-cell leukemia (ATL) accompanied with eosinophilia is described. A 75 year-old female was admitted to our hospital because of lymphadenopathy. Her leukocyte count was 73,300/microliters, with 35.5% abnormal lymphocytes and 19% eosinophils. A majority of lymphocytes expressed CD4+CD8-. Acute ATL was diagnosed, since anti-HTLV-1 antibody in her serum and monoclonal integration of HTLV-1 proviral DNA in her peripheral mononuclear cells were detected. She was treated with THP-adriamycin, cyclophosphamide (CPA), and vincristine (VCR). Abnormal lymphocyte and eosinophil counts decreased and there was improvement in the lymphadenopathy. However she then complained of lymphadenopathy again. Her leukocyte count rose to 76,300/microliters, with 89% abnormal lymphocytes. Combination therapy with CPA, VCR, and doxorubicin was started and there was a temporal regression in lymphadenopathy, but her lymphadenopathy recurred and she died. The activity of granulocyte-macrophage colony-stimulating factor (GM-CSF) was detected in the supernatant of the cultured ATL cells, although interleukin 3, interleukin-5, and GM-CSF activities were not detected in her serum. It seems likely that the secretion of GM-CSF by ATL cells are responsible for the eosinophilia. PMID- 8450614 TI - [Primary splenic lymphoma complicated by malignant rheumatoid arthritis and bladder cancer]. AB - A 64-year-old man had been found to have primary splenic lymphoma (stage III) seven years after the diagnosis of rheumatoid arthritis (RA). Histological diagnosis of the lymphoma was diffuse, medium sized cell type (LSG) or intermediate lymphocytic lymphoma (ILL). Splenectomy and ten courses of CHOP regimen produced continuing remission. After tow years, he suffered from peripheral neuropathy due to vasculitis of polyarteritis nodosa (PN) type. He was treated with prednisolone (PSL) and cyclophosphamide (CPM) for malignant rheumatoid arthritis. One year later, evaluation for intermittent hematuria revealed bladder cancer and he underwent total cystectomy. He has been treated with small doses of PSL under observation. The high incidence of ILL in lymphomas developing in patients with autoimmune diseases of the thyroid and salivary glands has been reported. This case suggests an association between antecedent RA and splenic lymphoma, the influence of splenectomy and chemotherapy on occurrence of rheumatoid vasculitis, and a causal relationship between CPM and bladder cancer. PMID- 8450616 TI - The 66th annual meeting of the Japanese Pharmacological Society. Yokohama, Japan, March 24-27, 1993. PMID- 8450615 TI - [Chronic myelogenous leukemia complicated with sarcoidosis]. AB - A 79-year-old man who had been diagnosed as having sarcoidosis when he was 63 year old, was admitted to our hospital because of marked thrombocytosis and leukocytosis in July 1991. The low neutrophil alkaline phosphatase (NAP) score, presence of Philadelphia (Ph1) chromosome in the bone marrow cells, and M-BCR rearrangement by Southern blot hybridization were observed. He was diagnosed as having chronic myelogenous leukemia complicated with sarcoidosis. The coexistence of sarcoidosis and leukemia has rarely been reported. It is difficult to discuss that there is not causal association between of them. PMID- 8450617 TI - [The safety of anesthesia. Part 2: risk of drugs]. PMID- 8450618 TI - [Principles of preventing undesirable effects due to changes of pharmacokinetic parameters during anesthesia]. PMID- 8450619 TI - [Prevention of undesirable effects during the use of opiate antagonists]. PMID- 8450620 TI - [Prevention of succinylcholine-induced undesirable effects]. PMID- 8450621 TI - [Prevention of undesirable effects during the use of non-depolarizing muscle relaxants]. PMID- 8450622 TI - [Prevention of undesirable effects during the use of anticholinergics and the antagonizing of muscle relaxants with cholinesterase antagonists]. PMID- 8450623 TI - [Side effects and risks in the use of nitrous oxide in the course of general anesthesia]. PMID- 8450624 TI - [Prevention of undesirable effects in the use of vasodilators]. PMID- 8450625 TI - [Undesirable effects in the use of local anesthetics]. PMID- 8450626 TI - [Risks of colloid solutions and hemodilution limits]. PMID- 8450627 TI - [Side effects of inhalation anesthetics and their prevention]. PMID- 8450628 TI - [Risks of the perioperative use of crystalloid and carbohydrate-containing solutions as basic and corrective therapy]. PMID- 8450629 TI - [Heparin and protamine--risk free?]. PMID- 8450630 TI - [Prevention of undesirable effects caused by drugs in obstetrical anesthesia]. PMID- 8450631 TI - [Computer-controlled anesthesia--more safety or increased risk?]. PMID- 8450632 TI - [Prevention of undesirable effects during the intravenous administration of barbiturates]. PMID- 8450633 TI - [Etomidate--propofol]. PMID- 8450634 TI - [Drug interactions: mechanisms and risks]. PMID- 8450635 TI - [Ketamine--unwanted effects and possible complications]. PMID- 8450636 TI - [Side effects and risks of benzodiazepine antagonism]. PMID- 8450637 TI - [Health as the hope from salvation]. PMID- 8450638 TI - [Nursing education--an utopia]. PMID- 8450639 TI - [Anne Rocksloh, nursing student]. PMID- 8450640 TI - [Attempted suicide--suicide--prevention. From the nurse's point of view. Part II and end]. PMID- 8450641 TI - [New pathways in continuing education. Concepts for the learning support in continuing education for the operating room]. PMID- 8450642 TI - [Practical guidelines in continuing education]. PMID- 8450643 TI - [Job description: practice guide]. PMID- 8450644 TI - [Model project: nursing of AIDS-patients]. PMID- 8450645 TI - Liver stem cells and development. PMID- 8450646 TI - Hepatocyte growth factor, blood clearance, organ uptake, and biliary excretion in normal and partially hepatectomized rats. AB - BACKGROUND: Hepatocyte growth factor (HGF) (also known as scatter factor (SF)) is a heterodimeric protein that is the most potent known complete mitogen for hepatocytes in culture. HGF is a mitogen for many epithelial cells including hepatocytes, kidney tubular epithelial cells, mammary epithelial cells, keratinocytes, etc. The protein encoded by the proto-oncogene c-met is the high affinity receptor for HGF. HGF concentration in the plasma dramatically increases after partial hepatectomy and in fulminant hepatic failure. This study describes the pharmacokinetics of HGF in the rat. EXPERIMENTAL DESIGN: Human recombinant HGF (a gift from Genentech) was radioiodinated and shown to retain biologic activity and structure. Approximately 74 ng of [125I]HGF was injected into the penile vein of male Fisher rats 5 minutes after a complete bile fistula and jugular venous catheterization were performed for blood and bile sampling. Half of the rats were subjected to 70% partial hepatectomy. RESULTS: The percentage of injected radioactivity present in the liver of control rats was 29.5% +/- 0.5% at 15 minutes and decreased to 8.6% +/- 1.0% at 120 minutes; the kidneys had 6.2% +/ 0.2% at 15 minutes, decreasing to 1.48% +/- 0.3% at 120 minutes. All the other organs examined had less than 1% of the injected radioactivity. The remaining radioactivity was present in low affinity sites in blood, bone, muscle, and skin. In control rats, radioactivity appeared in the bile within 3 minutes, reached a peak between 40 to 50 minutes, and tapered thereafter for a total 2-hour collection of 2.3% +/- 0.5%. In the partially hepatectomized rats, the HGF blood clearance was decreased (partial hepatectomy = 0.27 +/- 0.03 ml/minute; control = 0.53 +/- 0.06 ml/minute, p < 0.006), and the terminal half-life prolonged (partial hepatectomy = 124 +/- 11 minutes; control = 83 +/- 10 minutes, p < 0.03). The initial half-life for HGF, as extrapolated from the chart, was estimated at 3.8 minutes in control rats. CONCLUSIONS: Liver is the principle organ for initial uptake of [125I]HGF; disappearance from the blood suggests multicompartment kinetics with a rapid phase and a slower phase; only a portion of the hepatic uptake appears in the bile; and partial hepatectomy decreases the blood clearance of [125I]HGF. These results are correlated with previous findings bearing on the role of HGF elevation after partial hepatectomy as a stimulus for transfer of hepatocytes from G0 to G1 early in liver regeneration after partial hepatectomy. PMID- 8450647 TI - Restricted canine distemper virus infection of oligodendrocytes. AB - BACKGROUND: Canine distemper virus, a morbillivirus induces multifocal demyelination in the central nervous system. The acute demyelination correlates with virus replication in brain cells, especially astrocytes. Observations in vivo and in vitro demonstrated degeneration of oligodendrocytes, the myelin producing cells. However, the mechanism of oligodendroglial degeneration in distemper remained unexplained. Infection of the myelin producing cells, the most obvious explanation for the phenomenon of demyelination, could not be supported by extensive searches for viral particles or antigens in these cells neither in vivo nor in vitro. EXPERIMENTAL DESIGN: In the present study, we combined in situ hybridization to visualize viral nucleic acid sequences with immunofluorescence for oligodendroglial antigens. RESULTS: The nonradioactive in situ hybridization technique in combination with contrast enhanced video microscopy allowed us to unequivocally demonstrate the presence of canine distemper virus nucleic acid sequences in cultured oligodendrocytes. Many oligodendrocytes close to infected foci in the brain cell cultures were found to contain viral nucleic acid sequences. Only 1% of the viral nucleic acid sequences containing oligodendrocytes also contained viral antigen. Canine distemper virus replication in these cells is clearly restricted. CONCLUSIONS: Different possibilities why oligodendrocytes do not support a productive virus infection and mechanisms by which such a restricted infection leads to oligodendroglial degeneration and ensuing demyelination are discussed. While our results have advanced our understanding of the pathogenesis of acute demyelination in distemper, they may also offer a possible explanation for the chronic progressive or even relapsing course of the disease. A restricted infection of the oligodendrocytes may be the mechanism by which canine distemper virus persists in the central nervous system. Virus persistence is probably a key event in many chronic viral induced inflammatory demyelinating diseases. PMID- 8450648 TI - Rabies and borna disease. A comparative pathogenetic study of two neurovirulent agents. AB - BACKGROUND: Rabies and Borna disease viruses have been regarded as classical neurotropic agents. Many pathogenetic similarities are shared by these two negative strand RNA viruses. In view of recently gained data on the virology and pathology of these two diseases, and up-to-date comparative pathogenetic study seems to be justified. EXPERIMENTAL DESIGN: This study is based on a survey of experimental and natural infections of laboratory animals and natural hosts. The morphologic damage to the nervous system has been evaluated by light and electron microscopy, with special emphasis on immunocytochemical methods. RESULTS: This comparative study disclosed that both viruses are transported inside axons, pass synapses and propagate along neuronal networks. At the sites of synaptic transfer, full virus particles can never be detected in the early phase of rabies virus infection; in Borna disease virus (BDV) infection, virus particles cannot be found in any phase of disease progression. Thus, a major difference exists between the two agents insofar as rabies virus is morphologically well characterized, whereas BDV has never been visualized in tissue sections. Furthermore, rabies virus infects only neurons, whereas BDV also infects glial cells. The host range and the scale of infection of extraneural tissues by both agents is extremely similar. CONCLUSIONS: These observations allow us to postulate that the synaptic transfer of both viruses likely ensures in the form of bare nucleocapsids (ribonucleoprotein-transcriptase complexes). While in the later phases of replication complete rabies virions are regularly assembled, BDV propagates within the central nervous system in an incomplete form, so that it remains morphologically imperceptible. Thus, BDV may appear in a complete, enveloped form only when exiting the host organism. The dissemination patterns of the two agents may be influenced by specific affinities to neurotransmitter receptor sites. It remains unresolved, why BDV readily infects non-neuronal central nervous system cells, while rabies virus remains restricted to neuronal elements. PMID- 8450649 TI - Expression of the colony stimulating factor-1 receptor (c-fms product) by cells at the human uteroplacental interface. AB - BACKGROUND: The hematopoietic growth factor colony-stimulating factor-1 (CSF-1) and its receptor (encoded by the proto-oncogene c-fms) are implicated in the regulation of human placental development. EXPERIMENTAL DESIGN: In this study, we have performed a detailed immunohistochemical localization of the CSF-1 receptor (CSF-1R) on cells of the uteroplacental interface in human first trimester pregnancy, supplemented by Northern blot, in situ hybridization, and flow cytometric analysis. CSF-1R expression by JEG-3 and JAR choriocarcinoma cells was also investigated. RESULTS: c-fms mRNA was detected in primary cultures of first trimester trophoblast and was localized to the extravillous cytotrophoblast columns streaming off the anchoring villi. CSF-1R was expressed by fetal Hofbauer cells in the mesenchyme of the chorionic villi, and this expression increased considerably from first trimester to term. No expression was seen on first trimester and term villous cytotrophoblast. CSF-1R expression on villous syncytiotrophoblast was absent at 6 weeks, strongest at 8-10 weeks, and faded by 12 weeks. First trimester extravillous cytotrophoblast columns were strongly and consistently positive for CSF-1R expression, as was the superficial shell of extravillous trophoblast over the maternal decidua. However, with deeper invasion and terminal differentiation into placental bed giant cells, this expression became weak or absent. Endovascular trophoblast was also only weakly positive for CSF-1R. At the implantation site itself, large numbers of decidual macrophages and CD3-, CD56bright large granular lymphocytes were seen. The macrophages expressed CSF-1R strongly, but large granular lymphocytes, decidual stromal cells, glandular epithelium, and endothelial cells were found to be negative for CSF-1R expression. No CSF-1R expression was detected in JAR choriocarcinoma cells, but CSF-1R was present in first trimester cultured trophoblast and JEG-3 choriocarcinoma cells, although this was shown to be intracellular. CONCLUSIONS: These results suggest that CSF-1 may regulate invasion and differentiation of human placental trophoblast, depending upon the spatial and temporal distribution of its receptor. CSF-1 may also influence placental development and function by acting via decidual and fetal macrophages, which are the other cell populations expressing the receptor. PMID- 8450650 TI - A Paneth cell specific zinc-binding protein in the rat. Purification and immunohistochemical localization. AB - BACKGROUND: Paneth cells are zinc-containing cells widely distributed in Lieberkuhn's crypts of small intestine in many species, but their function has remained obscure. Our previous study showed that a single intravenous injection of diphenylthiocarbazone (dithizone), a zinc chelator, forms zinc-dithizonate complexes in the cytoplasm of Paneth cells to ensure rapid and selective killing of the cells. EXPERIMENTAL DESIGN: To verify the proteins that selectively deleted from intestinal mucosa after dithizone treatment, intestinal proteins from the rats with or without dithizone injection were compared in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. One such protein, a 90 kilodalton (kd) protein, was purified to homogeneity from normal rat intestine. A polyclonal antiserum was prepared by immunizing a rabbit with purified 90 kd protein to use in immunohistochemical study. RESULTS: Among several proteins deleted after dithizone injection, a 90 kd protein with an isoelectric point of 5.9 +/- 0.2, was purified to homogeneity from normal intestine by a combination of zinc affinity column and electroelution. Immunohistochemistry with rabbit anti-90 kd antiserum showed that the cytoplasmic granules in Paneth cells were stained. After dithizone administration, the 90 kd protein containing cells rapidly disappeared, but resumed as Paneth cells regenerated. Also positively stained with this antibody were a few mononuclear cells broadly distributed in the lamina propria of the digestive tract, but they were not affected by dithizone treatment. CONCLUSIONS: A 90 kd zinc-binding protein was identified and purified from rat Paneth cells that was deleted in dithizone-treated rat intestine. We propose to designate it as a zinc-binding protein of Paneth cell. PMID- 8450651 TI - Detection of prolactin messenger RNA in mammary and other normal and neoplastic tissues by polymerase chain reaction. AB - BACKGROUND: Although prolactin (PRL) is produced predominantly by the anterior pituitary gland, recent studies have found PRL in normal brain tissues and in various neoplasms. Many of these studies have used immunohistochemical methods to detect PRL production, so the distinction between de novo synthesis and uptake by tissues with PRL receptors was not possible with these approaches. PRL production by various neoplasms has been designated as ectopic, since it was assumed that non-neoplastic cells were not producing this hormone. EXPERIMENTAL DESIGN: The reverse transcriptase polymerase chain reaction technique (RT-PCR) was used to detect PRL mRNA in various normal rat tissues and normal and neoplastic human tissues. The sensitivity of RT-PCR to detect amplified products starting with very low amounts of total RNA was also determined. Amplified DNA was detected by ethidium bromide staining, Southern hybridization with 32P-labeled probes and with a chemiluminescent method. RESULTS: PRL expression was readily detected in normal rat brain and pituitary. One fg of starting total pituitary RNA was sufficient to detect PRL expression with RT-PCR. PRL was detected in human hypothalamus, cerebellum, and normal breast tissues (3/4 cases) as well as in breast carcinomas (5/7 cases). A lung, an endometrial and a medullary thyroid carcinoma also expressed PRL. The chemiluminescent detection system was as sensitive as 32P-labeled probes in detecting the amplified PCR product. CONCLUSIONS: These results indicate that PRL gene expression is present in normal and neoplastic mammary and other tissues and can be readily detected by RT-PCR. PMID- 8450652 TI - Methods in laboratory investigation. Rapid and simple detection of c-Ki-ras2 gene codon 12 mutations by nonradioisotopic single-strand conformation polymorphism analysis. AB - BACKGROUND: To achieve simple and rapid detection of codon 12 mutations of the c Ki-ras2 gene, we developed a nonradioisotopic single-strand conformation polymorphism analysis using silver stain. EXPERIMENTAL DESIGN: After a conventional polymerase chain reaction, amplified DNA fragments were mixed with formamide, heated and subjected to electrophoresis for 1.5 hours using minigels of polyacrylamide. The gels were then silver stained and single-strand DNA fragments were visualized directly. RESULTS: Electrophoresis and subsequent silver staining were completed within 2.5 hours. Plasmids carrying various codon 12 mutations of the c-Ki-ras2 gene were used as controls of Nonradioisotopic single-strand confirmation polymorphism analysis, and all six mutations were successfully separated from the normal allele in a single electrophoretic run. In the analysis of tumor cell lines and tumor samples, the results were identical with those of conventional dot blot hybridization using 32P-labeled oligonucleotide probes. Of 10 colorectal carcinoma tissues examined, 4 tumors were shown to carry codon 12 mutations of the c-Ki-ras2 gene. CONCLUSIONS: We conclude that this novel technique is a rapid, simple and useful method that may replace conventional methods. PMID- 8450653 TI - Tetranectin in the stroma of tumors. PMID- 8450654 TI - Four new speech and prosody-voice measures for genetics research and other studies in developmental phonological disorders. AB - Research in developmental phonological disorders, particularly emerging subgroup studies using behavioral and molecular genetics, requires qualitative and continuous measurement systems that meet a variety of substantive and psychometric assumptions. This paper reviews relevant issues underlying such needs and presents four measurement proposals developed expressly for causal correlates research. The primary qualitative system is the Speech Disorders Classification System (SDCS), a 10-category nosology for dichotomous and hierarchical polychotomous classification of speech disorders from 2 years of age through adulthood. The three quantitative measures for segmental and suprasegmental analyses are (a) the Articulation Competence Index (ACI), an interval-level severity index that adjusts a subject's Percentage of Consonants Correct (PCC) score for the relative percentage of distortion errors; (b) Speech Profiles, a series of graphic-numeric displays that profile a subject's or group's severity-adjusted consonant and vowel-diphthong mastery and error patterns; and (c) the Prosody-Voice Profile, a graphic-numeric display that profiles a subject's or group's status on six suprasegmental domains divided into 31 types of inappropriate prosody-voice codes. All data for the four measures are derived from one sample of conversational speech, which obviates the limitations of citation-form testing; enables speech assessment as a qualitative, semi continuous, and continuous trait over the life span; and provides a context for univariate and multivariate statistical analyses of phonetic, phonologic, prosodic, and language variables in multiage, multidialectal, and multicultural populations. Rationale, procedures, validity data, and examples of uses for each measure are presented. PMID- 8450656 TI - Relative satisfaction for frequency responses selected with a simplex procedure in different listening conditions. AB - The purpose of this study was to compare everyday satisfaction with hearing aid frequency responses selected using a Simplex procedure and those selected using the National Acoustic Laboratories' formula (NAL-R). Nineteen elderly subjects with impaired hearing selected their preferred frequency responses under six listening conditions. The conditions included syllable identification and discourse quality judgement in quiet, in moderate noise (65 dB SPL), and in loud noise (80 dB SPL) backgrounds. Subjects subsequently wore a multimemory hearing aid programmed with these frequency responses and compared their satisfaction with the various frequency responses in daily listening environments. Subjects showed differential preference across the available frequency responses. Subjects with sloping hearing losses did not show a difference in preference among the selected frequency responses, including that prescribed by NAL-R. On the other hand, subjects with a flat hearing loss showed a slight, but consistent, preference for frequency responses selected while listening to discourse passages in a moderate noise background. These observations suggest that the Simplex procedure may be useful for selecting preferred frequency responses for some hearing aid wearers. PMID- 8450655 TI - Comparing internal and external standards in voice quality judgments. AB - A new descriptive framework for voice quality perception (Kreiman, Gerratt, Kempster, Erman, & Berke, 1993) states that when listeners rate a voice on some quality dimension (e.g., roughness), they compare the stimulus presented to an internal standard or scale. Hypothetically, substituting explicit, external standards for these unstable internal standards should improve listener reliability. Further, the framework suggests that internal standards for vocal qualities are inherently unstable, and may be influenced by factors other than the physical signal being judged. Among these factors, context effects may cause drift in listeners' voice ratings by influencing the internal standard against which judgments are made. To test these hypotheses, we asked 12 clinicians to judge the roughness of 22 synthetic stimuli using two scales: a traditional 5 point equal appearing interval (EAI) scale and a scale with explicit anchor stimuli for each scale point. The stimulus set included a relatively large number of normal and mildly rough voices. We predicted that this would produce an increase in the perceived roughness of moderately rough stimuli over time for the EAI ratings, but not for the explicitly anchored ratings. Ratings made using the anchored scale were significantly more reliable than those gathered using the unanchored paradigm. Further, as predicted, ratings on the unanchored EAI scale drifted significantly within a listening session in the direction expected, but ratings on the anchored scale did not. These results are consistent with our framework and suggest that explicitly anchored paradigms for voice quality evaluation might improve both research and clinical practice. PMID- 8450657 TI - Multiple frequency tympanometry: effects of ear canal volume compensation on static acoustic admittance and estimates of middle ear resonance. AB - Three methods for compensating multiple frequency acoustic admittance measurements for ear canal volume were studied in 26 men with normal middle ear transmission systems. Peak compensated static acoustic admittance (magnitude of y) and phase angle (phi) were calculated from sweep frequency tympanograms (226 1243 Hz in 113 Hz increments). Of the procedures used to compensate for volume in rectangular form, the ear canal pressure used to estimate volume had the largest effect on the estimate of middle ear resonance. Median resonance was 800 Hz for admittance measurements compensated at 200 daPa versus 1100 Hz for measurements compensated at -350 daPa. The remaining two methods, compensation of susceptance only versus both susceptance and conductance and compensation using the minimum volume versus separate volumes at each frequency, did not affect estimates of middle ear resonance. Estimates of middle ear resonance from compensated phase angle measurements also were compared with estimates of resonance from admittance and phase difference curves. Although resonance could not be estimated from the phase difference curve, resonance estimated from the admittance difference curve agreed with the estimate from compensated phase angle. PMID- 8450658 TI - Speech intelligibility of children with cochlear implants, tactile aids, or hearing aids. AB - Speech intelligibility was measured in 31 children who used the 3M/House single channel implant (n = 12), the Nucleus 22-Channel Cochlear Implant System (n = 15), or the Tactaid II + two-channel vibrotactile aid (n = 4). The subjects were divided into subgroups based on age at onset of deafness (early or late). The speech intelligibility of the experimental subjects was compared to that of children who were profoundly hearing impaired who used conventional hearing aids (n = 12) or no sensory aid (n = 2). The subjects with early onset of deafness who received their single- or multichannel cochlear implant before age 10 demonstrated the highest speech intelligibility, whereas subjects who did not receive their device until after age 10 had the poorest speech intelligibility. There was no obvious difference in the speech intelligibility scores of these subjects as a function of type of device (implant or tactile aid). On the average, the postimplant or tactile aid speech intelligibility of the subjects with early onset of deafness was similar to that of hearing aid users with hearing levels between 100 and 110 dB HL and limited hearing in the high frequencies. The speech intelligibility of subjects with late onset of deafness showed marked deterioration after the onset of deafness with relatively large improvements by most subjects after they received a single- or multichannel implant. The one subject with late onset of deafness who used a tactile aid showed no improvement in speech intelligibility. PMID- 8450659 TI - Real ear to 6-cm3 coupler differences in young children. AB - Real-ear sound pressure levels under supra-aural earphones were measured for a group of young children (9 months to 7 years) and adults. Pure-tone signals were presented at nine test frequencies from 250 to 6000 Hz, and real ear to 6-cm3 coupler differences were computed for each frequency. Results suggest that, by 2 years of age, average real ear to 6-cm3 coupler differences are similar for adults and children. The intersubject variability for all groups supports the need for real-ear threshold measures on an individual basis in cases where the ability to amplify the speech spectrum to a level that is audible across the frequency range is in question. PMID- 8450660 TI - Perceptual evaluation of voice quality: review, tutorial, and a framework for future research. AB - The reliability of listeners' ratings of voice quality is a central issue in voice research because of the clinical primacy of such ratings and because they are the standard against which other measures are evaluated. However, an extensive literature review indicates that both intrarater and interrater reliability fluctuate greatly from study to study. Further, our own data indicate that ratings of vocal roughness vary widely across individual clinicians, with a single voice often receiving nearly the full range of possible ratings. No model or theoretical framework currently exists to explain these variations, although such a model might guide development of efficient, valid, and standardized clinical protocols for voice evaluation. We propose a theoretical framework that attributes variability in ratings to several sources (including listeners' backgrounds and biases, the task used to gather ratings, interactions between listeners and tasks, and random error). This framework may guide development of new clinical voice and speech evaluation protocols, ultimately leading to more reliable perceptual ratings and a better understanding of the perceptual qualities of pathological voices. PMID- 8450661 TI - The effect of otitis media with effusion on the masking-level difference and the auditory brainstem response. AB - This study investigated the masking-level difference (MLD) and auditory brainstem response (ABR) in a group of children with a history of otitis media with effusion (OME) and a control group of children with no known history of ear disease. All children had normal hearing at the time of testing. The main goal of the study was to determine whether there was an association between a reduced MLD in the OME children and an abnormal ABR (in terms of prolonged absolute or interwave intervals, or interaural differences in the ABR waveforms). The results indicated that the group of children having a history of OME had significantly reduced MLDs and had significantly prolonged waves III and V, and I-III and I-V interwave intervals. The correlations between MLD and delays in absolute wave or interwave intervals were not significant. However, some correlations between interaural asymmetries of the interwave intervals and the MLD were significant. The results suggest that the reduction in MLD found in children having a history of OME may be related to abnormal brainstem processing. PMID- 8450662 TI - Middle ear resonance and acoustic immittance measures in children. AB - This study established a normal middle ear resonance estimated from sweep frequency tympanometry (250-2000 Hz) and established normal equivalent ear canal volume, static acoustic admittance, and tympanometric peak pressure at 226 Hz in children with normal hearing (N = 90) and in children with severe to profound sensorineural impairments (N = 68). Children's ages ranged from 6 to 15 years. No statistically significant differences between the groups or across ages were found. Means, standard deviations, and 90% ranges (5-95%) for these four tympanometric measures are presented and compared to other studies. PMID- 8450663 TI - Preschoolers' imitation of intonation contours. AB - This study evaluated normally developing preschoolers' imitation of intonation contours modeled in a sentence elicitation task. Three intonation contours (declarative, interrogative, and monotone) were presented to 3- and 5-year-old children. Acoustic analyses using the Visi-Pitch and Apple IIe computer system, along with perceptual ratings, measured the extent to which preschoolers imitated a modeled intonation contour. The results indicated that, as a group, the children were perceived to imitate or partially imitate the preceding intonation contour modeled by the adult. The 5-year-old children imitated modeled contours more frequently than did the 3-year-old children. In contrast, the 3-year-old children primarily partially imitated the intonation contours. Further analysis revealed that between-group differences were due largely to accuracy in imitating the interrogative contour. These findings establish reference data on normal children and implicate the use of both acoustic and perceptual analyses in order to develop and interpret intervention strategies aimed at children with prosodic problems. PMID- 8450664 TI - Speaking rate and speech movement velocity profiles. AB - The effects of speaking rate on the velocity profiles of movements of the lower lip and tongue tip during the production of stop consonants were examined using an x-ray microbeam system. Five young adults used a magnitude production task to produce five speaking rates that ranged from very fast to very slow. Results indicated that changes in speaking rate were associated with changes in the topology of the speech movement velocity-time function. Specifically, the velocity profile changed from a symmetrical, single-peaked function at the fast speaking rates to an asymmetrical and multi-peaked function at the slow speaking rates. This variation in velocity profile shape is interpreted as support for the view that alterations in speaking rate are associated with changes in motor control strategies. In particular, the control strategy for speech gestures produced at fast speaking rates appears to involve unitary movements that may be predominantly preprogrammed, whereas gestures produced at slow speaking rates consist of multiple submovements that may be influenced by feedback mechanisms. PMID- 8450665 TI - Physiological differences between stutterers and nonstutterers in perceptually fluent speech: EMG amplitude and duration. AB - Electromyograph (EMG) signals of the m. orbicularis oris inferior evoked by lip rounding gestures were analyzed to see whether stutterers in their perceptually fluent speech had higher levels of EMG and longer EMG durations. The relationship between levels of EMG and durations of elevated muscle activity was investigated, and a search for the best discriminating EMG measure was made. In contrast to some previous studies on the EMG signals of stutterers, a relatively large group of stutterers (n = 15) and control speakers (n = 20), matched for age and gender, was examined. Both groups took part in a reaction time experiment using verbal items of different length (syllables, words, and sentences) in two time-stress conditions. Measures were taken for lip muscle activity during lip-rounding gestures for the Dutch /o/ sound. Only perceptually fluent trials were analyzed. The results showed that stutterers had significantly higher EMG levels at the moment of speech onset and during speech production than nonstutterers. A much larger difference between the two groups, however, was found for the EMG peak latency measure, which proved to be a very powerful distinctive feature in differentiating stutterers from nonstutterers. The results were discussed with respect to previous findings and recent theories about (speech) motor control strategies. PMID- 8450666 TI - Respiratory and laryngeal function of women and men during vocal intensity variation. AB - Simultaneous procedures for making aerodynamic and kinematic observations of the laryngeal and chest wall systems were used to investigate variations in vocal intensity in normal women and men. Laryngeal results indicate that significant increases of maximum flow declination rate and laryngeal airway resistance and significant decreases in open quotient occur when higher intensity levels are produced. Respiratory results indicate that tracheal pressure, percent rib cage contribution, lung volume, and rib cage volume initiations are higher, and lung and rib cage volume excursions are larger when higher vocal intensity levels are produced. Laryngeal and respiratory function results indicate that some measures are different for women than for men. Mean data support the notion that increases in tracheal pressure are achieved by inhaling to higher lung and rib cage volumes. Individual subject data provide alternative respiratory and laryngeal patterns for changing the shape of the glottal airflow waveform. PMID- 8450667 TI - Verbal analogical reasoning in children with language-learning disabilities. AB - This study was designed to explore the influences of both cognitive and linguistic abilities on verbal analogy completion. School-age children classified as language-learning disabled were administered five types of verbal analogies: synonyms, antonyms, linear order, category membership, and functional relationship. The performance of the children with language-learning disabilities was compared with one group of normally developing children matched for mental age and another group matched for language age. Results indicated that the group matched for mental age performed better than the other two groups on all types of analogies. Although they had significantly higher mental ages, the children with language-learning disabilities did no better than the language-matched group on any analogy type except antonyms. PMID- 8450668 TI - Haptic recognition of children with specific language impairment: effects of response modality. AB - Children with specific language impairment (SLI) have been shown to exhibit deficient nonlinguistic symbolic functioning as indexed by their poor haptic recognition. Previous findings from conventional haptic tasks may be confounded because subject responses required cross-modal processing. The present study compared the haptic processing of children with SLI and children with normal language (NL) using one cross-modal and two tactile response conditions to isolate the influence of cross-modal processing on haptic recognition. Results showed that children with SLI and those with NL performed (a) similarly when the response modality was tactile and task requirements were minimal and (b) differently when the response demands included cross-modal processing or increased symbolic and memory processing. The results were interpreted to suggest that (a) children with SLI and those with NL possess comparable nonlinguistic representational abilities as indexed by haptic processing and (b) deficient cross-modal processing and limited capacity processing are two likely sources of the overall poorer haptic functioning of children with SLI. PMID- 8450669 TI - Leukemia and electromagnetic fields. PMID- 8450670 TI - Minimally differentiated acute leukemia. AB - We have studied 35 adult patients with morphologically undifferentiated peroxidase-negative acute leukemia that failed to meet the criteria for acute lymphoblastic leukemia and compared them to patients with FAB M1-M7 seen by the same physicians. The diagnosis of minimally differentiated acute leukemia (MD-AL) was associated with a higher incidence of prior hematologic disease, lower WBC, fewer blood blasts, lower marrow cellularity and a tendency towards older age. Of all patients treated with AML since January 1983, those with MD-AL were less likely to get a complete remission than those with other subtypes (35 vs 64%, p = 0.03). Treatment failure was usually due to resistant disease. Analysis of outcome as a function of drugs used during induction therapy showed an advantage for regimens containing vincristine and prednisone. The leukemic blast cells of nine patients were immunophenotyped for myeloid, lymphoid and megakaryoblast/platelet antigens. Although there were too few for a full statistical analysis as was applied to the larger group of 35 patients with MD AL, these patients had a lower bone marrow cellularity as compared to FAB M1-M7 and a low remission rate. Eight of these were found to have positive myeloid markers and met the criteria for FAB M0. We conclude that patients with MD-AL form a distinct group with characteristic presenting features and a low response rate. Outcome data suggest that vincristine and prednisone should be included in experimental induction programs. PMID- 8450671 TI - Altered properties of human T-lymphoblast soluble low Km 5'-nucleotidase: comparison with B-lymphoblast enzyme. AB - Soluble low Km 5'-nucleotidases have been purified from human cultured T- and B lymphoblasts to compare their properties and to examine the mechanism of different rates of nucleotide dephosphorylation. The enzyme from B-lymphoblasts (MGL-8) was 4385-fold purified with a specific activity of 114 mumol/min/mg, while the enzyme from T-lymphoblasts (CEM, MOLT-4) was 4355-fold purified with a specific activity of 35 mumol/min/mg. The activity of both enzymes have an absolute requirement for Mg++. The B-cell enzyme has maximum activity with Mg2+ > Mn2+ > Co2+, while the T-cell enzyme had maximum activity with Co2+ > Mn2+ > Mg2+. The optimum activity was at pH 7.4-9.0 for the B-cell enzyme and pH 9.0 for the T-cell enzyme. Substrate specificity was the same for both enzymes with the following relative Vmax values: CMP > UMP > dUMP > dCMP > dAMP > IMP > GMP > dIMP > dGMP. The Km values for AMP and IMP were 12 and 25 microM for the B-cell enzyme, and 7.0 and 12 microM for the T-cell enzyme. ATP and ADP are competitive inhibitors of these enzymes with apparent Ki values of 100 and 20 microM for the B-cell enzyme, and 44 microM and 8 microM for the T-cell enzyme, respectively. The apparent molecular mass by gel filtration column chromatography is 145 kD for the B-cell enzyme and 72 kDa for the T-cell enzyme. The subunit molecular masses by Western blots are 69.2 kD for both enzymes. These properties suggest that the B-lymphoblast enzyme is identical or similar to the enzyme from human placenta. However, the T-cell enzyme has some different properties. We conclude that these differences plus a lower content of low Km 5'-nucleotidase in T-cells may account for the decreased ability of T-lymphoblasts to dephosphorylate nucleotides and may contribute to the selective cytotoxicity of deoxyribonucleosides for T lymphoblasts as compared to B-lymphoblasts. PMID- 8450672 TI - Evidence that endogenous generation of leukotrienes does not regulate proliferation of malignant hemopoietic cell lines. AB - The proliferation of malignant hemopoietic cell lines is inhibited by antagonists of 5-lipoxygenase, suggesting that the endogenous generation of leukotrienes via the action of this enzyme may play some role in the proliferation of these cells (Snyder D. S., Castro R. & Desforges J. F. (1989), Expl Hemat. 17, 6). Here we have confirmed that the lipoxygenase inhibitors piriprost, nordihydroguiaretic acid and BW755C decreased DNA synthesis and proliferation of leukemic cell lines. However, the concentrations of these drugs required for half-maximal inhibition of proliferation were significantly greater than their IC50 values for 5 lipoxygenase inhibition. We therefore studied the actions of two novel, potent lipoxygenase inhibitors, BWA4C and MK886, on proliferation (as measured by estimating the number of viable, trypan blue-excluding cells) and DNA synthesis (measured by the incorporation of radiolabeled thymidine) in the leukemia cell lines HL60, K562 and Jurkat. Neither parameter was affected by concentrations of these drugs which were shown in parallel studies to substantially inhibit leukotriene generation in whole blood. The data show that endogenous leukotriene generation does not play a significant role in the regulation of proliferation of these leukemic cell lines and suggest that conclusions about leukotriene involvement in the control of cellular metabolic pathways based on the use of lipoxygenase inhibitors should be re-assessed. PMID- 8450673 TI - Sensitivity of committed hematopoietic progenitor cells in vitro (BFU-E, CFU-E, CFU-GM) and two human carcinoma cell lines toward rhodamine-123 and phosphonium salt II-41. AB - Lipophilic cationic compounds accumulate more rapidly in the mitochondria of many carcinoma-derived cells than in non-transformed cells, thus leading to their pronounced cytotoxic effects on carcinoma cells. In this report, in order to measure tumoricidal effects vs cytotoxicity to normal hematopoietic progenitors, we studied the sensitivity of committed human hematopoietic cells in vitro and two human carcinoma cell lines (2008 ovary carcinoma cells and HT29 colon cells) toward two such compounds, rhodamine-123 and phosphonium salt II-41. Continuous exposure of human marrow cells to rhodamine-123 or phosphonium salt II-41 for 7 and 14 days produced dose-related inhibition of colony formation of erythroid burst-forming units (BFU-E), erythroid colony forming units (CFU-E), and CFU granulocyte/macrophage (CFU-GM). The average values of IC50 for several different human bone marrows are approximately 0.9-1.1 microM for rhodamine-123 toward BFU E, CFU-E and CFU-GM, and 31-38 microM for phosphonium salt II-41 toward the same hematopoietic progenitors. These IC50 values are similar for each type of hematopoietic progenitors. In each case, rhodamine-123 appears to be at least 30 fold more growth suppressive than phosphonium salt II-41 in these in vitro colony assays. In addition, the sensitivity of these hematopoietic progenitors toward these two compounds is comparable to the inhibition of colony formation for the two human carcinoma cell lines. The lack of differences in the sensitivity among the various hematopoietic progenitors in vitro may disagree with previous studies showing there are vast differences in the state of cell cycle for these hematopoietic progenitor cells. However, these observations about the cytotoxicity in vitro can be explained by assuming that the cytotoxicity of these compounds depends on other factors such as differentiation processes, which result in the appearance of many or very active mitochondria. Alternatively, the lack of differences in the sensitivity of the in vitro colony formation can also be attributed to a reported decrease in expression of P-glycoprotein, a multidrug efflux pump, in the differentiating hematopoietic progeny cells. PMID- 8450674 TI - Adhesive capacity of human long-term bone marrow cultures from normals and patients with acute myeloid leukaemia: the influence of adhesion molecules. AB - In order to study the adhesive interactions of the human bone marrow microenvironment and acute myeloid leukaemic cells, we investigated the binding capacity of KG-1 cells upon human long-term bone marrow cultures derived from 17 healthy volunteers and 12 patients with acute myeloid leukemia. Adhesion was measured using a 51-chromium labelling assay. Adhesion of KG-1 cells upon 'normal' stromal layers: 33% +/- 4.0, n = 17 (mean +/- SEM) was higher as compared to the binding to 'leukaemic' stromas: 24% +/- 3.7, n = 12 (p < 0.05). Blocking monoclonal antibodies against adhesion molecules reduced the binding of KG-1 cells upon 'normal' stroma, when anti-VLA4 (p < 0.03), anti-Mac1 (p < 0.03) and anti-p150/95 (p < 0.04) were used. Binding of KG-1 cells on 'leukaemic' stromas was partly inhibited by anti-VCAM1 (p < 0.03). Blocking achieved by single or combined antibodies was never complete, suggesting that the adhesion is a multifactorial process, including a variety of adhesion molecules and/or adhesion mechanisms. PMID- 8450675 TI - Temperature dependence of glucocorticoid binding in sensitive and refractory murine leukaemia cells. AB - The validity of in vitro assays in predicting the susceptibility of leukaemic cells to glucocorticoid-mediated lysis was evaluated in a panel of six murine leukaemia cell lines. In this panel susceptibility to glucocorticoids ranged from highly sensitive to fully resistant. The panel was screened for specific 3H dexamethasone binding in whole cells and for activation of cytosolic receptors in cell lysates. Specific binding of 3H-dexamethasone was strongly affected by the incubation temperature. In all cell lines, rapid and reversible changes were observed in the stability of agonist-receptor association with a transition temperature of 28 degrees C. Below this temperature, intracellular receptors were found to be in a stable-binding, high-affinity configuration, masking differences in receptor status among the various cell lines. When assayed at 37 degrees C, refractory and fully resistant cells revealed nonsaturating, low-affinity binding of steroid. Saturating, high-affinity binding was, however, restored in these cells by the drug meta-iodobenzylguanidine with concomitant sensitization to dexamethasone-induced lysis. Contrary to observations with intact cells, heat induced agonist-receptor dissociation in cytosols caused irreversible loss of (re)binding capacity. Activation of cytosolic receptors only recognized fully resistant cell lines as being deficient in the transformation of liganded receptors into a DNA-binding configuration. The assay, however, could not discriminate between three cell lines with highest but varying degrees of sensitivity because of maximal activation. The results indicate that non physiological temperature and cell disruption strongly and differentially affect steroid binding and receptor activation, respectively. The observations may account for the poor correlation between conventional predictive assays and steroid responsiveness in clinical leukaemia. PMID- 8450677 TI - Development of screeners for depressive disorders and substance disorder history. AB - If screeners are going to be widely incorporated in clinical care to increase the detection of common psychiatric disorders, they need to be brief, easy to score, and sensitive across diverse patient populations. Few screeners exist that meet these criteria. This problem is addressed in this study by identifying a subset of questions from the Diagnostic Interview Schedule (DIS), which predicted simultaneously obtained DIS diagnoses. A two-item screener to detect depression or dysthymia within the last year and three-item screeners for lifetime drug disorders and alcohol disorders were tested in community residents, medical, and mental health patients. The sensitivity of the depression screener ranged between 83% and 94%. The sensitivity of the drug screener ranged between 91% and 94%, excluding one site with an extremely low prevalence of drug problems. The sensitivity of the alcohol screener ranged between 87% and 92%. Specificity for all three screeners exceeded 90% in community and medical samples, while being somewhat lower among mental health patients. These findings indicate that these brief screeners may be useful in a variety of epidemiologic studies to provide estimates of common psychiatric disorders when complete diagnostic interviews are not feasible. If further validation studies support these sensitivity and specificity estimates, these new instruments may also be valuable as initial brief screeners in a two-stage screening process to improve clinicians' recognition of common mental health problems that complicate case management and impair patient functioning. PMID- 8450676 TI - Fatal spleen rupture during induction chemotherapy with rh GM-CSF priming for acute monocytic leukemia. Clinical case report and in vitro studies. AB - Recombinant human (rh) granulocyte-macrophage colony-stimulating factor (GM-SCF) is currently being tested in clinical trials for the treatment of acute myeloid leukemias with two main intentions: reduction of neutropenia and recruitment of leukemic blasts into cell cycle to enhance cytarabine (ara-C) mediated cytotoxicity. We report a case of a fatal spleen rupture in a patient with acute monocytic leukemia (AML M5b) who was treated according to a clinical phase I/II protocol with rh GM-CSF priming and standard induction chemotherapy TAD 9 (thioguanine/ara-C/daunorubicin). During treatment we observed rapidly rising peripheral blast counts and the development of an acute abdomen. Ultrasound examination revealed splenomegaly due to diffuse cellular infiltration and spleen rupture. The patient died 17 days later due to pneumonia and renewed spleen hemorrhage. Bone marrow progenitor assays before treatment showed exclusive growth of monocytoid blast cell colonies (CFU-L). Colony growth could be stimulated with rh GM-CSF and blocked dose-dependently by a monoclonal anti-GM CSF antibody. CFU-L proliferation also increased after stimulation with rh interleukin-3 (rh IL-3) and supra-additively with rh granulocyte colony stimulating factor (rh G-CSF) combined with rh GM-CSF. Furthermore, rh GM-CSF induced surface marker expression of CDw 65 and CD 11b on isolated CFU-L blasts. After short-term suspension culture, rh GM-CSF enhanced the expression of CD 29- and CD 11b-adhesion molecules on peripheral blast cells. In summary, this case represents a fatal spleen rupture occurring during rh GM-CSF priming and induction chemotherapy for acute monocytic leukemia. Although the etiology of this spleen rupture remains uncertain, in view of our data we suggest special caution, when further testing this therapy protocol in acute leukemias with monocytic subtype and high peripheral blast cell counts. PMID- 8450678 TI - Registries and administrative data: organization and accuracy. AB - In this article the organization and accuracy of the population registry and administrative data base in Manitoba, Canada are discussed. The overall data management strategy and a framework for analyzing the accuracy of such data are presented. The generally high quality of the Manitoba registry file (necessary to track individuals over time) and the hospital claims is supported by comparisons with other data sources. Hospital claims' main quality problems concern the reliability of certain secondary diagnoses and the level of aggregation necessary for reasonable agreement with other data collection methods (such as chart reviews). Finally, some of the research possibilities associated with population registries and administrative data are outlined. PMID- 8450679 TI - Physician gender bias in clinical decisionmaking: screening for cancer in primary care. AB - There has been increasing interest in gender disparities in clinical decisionmaking. Few studies have examined this issue in nationally representative samples or focussed on primary care. In addition, few of the studies have examined the role of physician gender. The 1987 National Medical Expenditure Survey was used to examine the relationship between physician gender and screening deficiency in women for three gender-sensitive tests (breast examinations, Papanicolaou tests, and mammograms) and one gender-neutral test (blood pressure checks). Women reporting a female physician as their usual provider compared with those reporting a male physician were less likely to be deficient for Papanicolaou tests and mammograms. There was a smaller, but nonsignificant similar trend for breast examinations. No gender bias was evident for blood pressure checks. These results persisted after multivariate adjustment for patient age, race, education, income, insurance status, subjective health status, other health behaviors, and attitude toward health care and health insurance. The results confirm the existence of physician gender bias in clinical decision making and represent one area for quality improvement. PMID- 8450680 TI - Gender differences in practice style: a Dutch study of general practitioners. AB - The differences between female and male general practitioners (GPs) were studied regarding three different factors: 1) Do female GPs see more female patients than their male colleagues in the same practice?; 2) Are female GPs confronted with different types of health problems from their male colleagues?; and 3) Do female GPs provide different services to their patients? Data from the Dutch National Study on Morbidity and Interventions in General Practice were used. All practices in this study with both female (n = 23) and male (n = 27) GPs were selected. This resulted in detailed data on 47,254 consultations, 62% of which were with female patients. The three research questions all received an affirmative response: 1) female patients tend to choose female general practitioners; 2) female GPs see different health problems from their male colleagues, and that is only partly because the patient so chooses; and 3) besides the expected differences in female specific problems, there is a clear GP-gender effect in the presence of 'social' and 'metabolic' problems in the female GP's consultations. Some differences in the provision of services between male and female GPs occurred, with female GPs spending more time on their patients and having a stronger tendency to provide continuity of care. In addition to a gender effect (both physician and patient) a part-time effect in most issues studied was observed. PMID- 8450681 TI - The MOS 36-Item Short-Form Health Survey (SF-36): II. Psychometric and clinical tests of validity in measuring physical and mental health constructs. AB - Cross-sectional data from the Medical Outcomes Study (MOS) were analyzed to test the validity of the MOS 36-Item Short-Form Health Survey (SF-36) scales as measures of physical and mental health constructs. Results from traditional psychometric and clinical tests of validity were compared. Principal components analysis was used to test for hypothesized physical and mental health dimensions. For purposes of clinical tests of validity, clinical criteria defined mutually exclusive adult patient groups differing in severity of medical and psychiatric conditions. Scales shown in the components analysis to primarily measure physical health (physical functioning and role limitations-physical) best distinguished groups differing in severity of chronic medical condition and had the most pure physical health interpretation. Scales shown to primarily measure mental health (mental health and role limitations-emotional) best distinguished groups differing in the presence and severity of psychiatric disorders and had the most pure mental health interpretation. The social functioning, vitality, and general health perceptions scales measured both physical and mental health components and, thus, had the most complex interpretation. These results are useful in establishing guidelines for the interpretation of each scale and in documenting the size of differences between clinical groups that should be considered very large. PMID- 8450682 TI - Delay from symptom to diagnosis and treatment of breast cancer in Washington State and British Columbia. PMID- 8450683 TI - Health status among persons infected with human immunodeficiency virus. A community-based study. PMID- 8450684 TI - MedisGroups data bases. The impact of data collection guidelines on predicting in hospital mortality. PMID- 8450685 TI - The National Asthma Education Program. Expert panel report guidelines for the diagnosis and management of asthma. National Heart, Lung, and Blood Institute. AB - The significant worldwide increase in asthma-related severity and mortality has evoked increasing concern from the medical community. To enhance early recognition and appropriate therapeutic intervention of asthma, the National Heart, Lung, and Blood Institute's National Asthma Education Program convened an expert panel to develop guidelines for the diagnosis and treatment of asthma. The guidelines discussed in this article emphasize that airway inflammation is a central characteristic of asthma. Appropriate therapy must include four components: the use of objective measures of lung function to assess the severity of asthma and to monitor the course of therapy, comprehensive pharmacologic therapy that includes medications to reverse and prevent the underlying airway inflammation and to relieve the bronchoconstriction, environmental control measures to avoid or control factors that precipitate asthma exacerbations, and patient education to foster a partnership among the patient, the patient's family, and the clinician. PMID- 8450686 TI - Patient and physician behavior models related to asthma care. AB - This article summarizes the considerable progress that has been made in characterizing the behaviors of patients and family members that contribute to good or poor outcomes of asthma care and in developing educational programs shown to be effective in improving patient outcomes. Research needs are identified, including the need for better understanding of the antecedents of patient behaviors and their relative (quantitative) contribution to outcomes of asthma care of techniques to alter patient and family management behavior to improve outcomes, especially among particular patient subgroups are described. In addition, the asthma management practices of physicians are examined, such as the frequency with which recommended versus less desirable approaches to the diagnosis and treatment of asthma are used. Critical to this research was the development or refinement and the standardization of measures of individual patient behavior (including compliance behaviors), asthma morbidity, and utilization of medical services related to asthma. PMID- 8450687 TI - Influence of organizational components on the delivery of asthma care. AB - The documented growing morbidity, mortality, and disability from asthma indicate a failure in effective delivery of appropriate care. This article reviews how different components of organizational technology in hospitals, free-standing emergency centers, physician practices, prepaid groups, and schools may be linked to asthma care and asthma outcomes. A framework to address how practice patterns, risk factors, and outcomes relate to organizational characteristics, such as time orientation, uncertainty, available technology, standardization of work, specialization of work, coordination, and control strategies, is presented. PMID- 8450688 TI - Financial payment systems and asthma care. AB - This paper addresses how medical care financing issues may impact on the process and outcome of asthma care. Because asthma-specific data are scarce, an attempt has been made to extrapolate from an understanding of payment issues for chronic illness in general to the specific case of asthma. First, some broad features of the effect of payment systems on health care delivery are reviewed. How financing of care for the individual patient affects financial access to care is then examined. Next, financing of care at the provider level is discussed, and fee-for service and prepaid systems are compared with respect to how individual patients with chronic illness may be treated differently. Financing at the health insurance plan level, particularly with regard to benefits and quality of care, then is explored. Finally, knowledge gaps are highlighted, as are some of the difficulties encountered in investigating this topic. PMID- 8450689 TI - Issues in the measurement of health status in asthma research. AB - Asthma is a chronic condition of increasing prevalence and high cost to patients, their families, and society. Research into the causes and consequences of asthma has increased during the last few years, but the use of health status measures to help characterize patient outcomes is infrequent. Those studies that have included health status measures have focused on different dimensions of health status, making comparisons across studies difficult. The purpose of this article is to provide information about the selection of health status measures in studies of persons with asthma and to review applications of and make recommendations for health status assessment in asthma research. These recommendations include: use of both generic and specific instruments where appropriate, the development of new asthma-specific measures and rigorous testing of the several new measures that have been reported recently, and the development and inclusion of utility measures in studies of asthma. PMID- 8450691 TI - Asthma health status. Ongoing measurement in the context of continuous quality improvement. AB - There are no widely accepted measures of health status for asthmatic patients, and these must be developed. Criteria for good health status measures are described. Their intended use determines their form. The concepts of continuous quality improvement (CQI) are used here to define a new perspective about asthma health status measures. In the context of CQI, a patient-centered continuous measurement can be used to understand and reduce variance in health status. Ongoing health status measures can be applied to groups of patients or individuals. Medical students collected data about the health status of their asthmatic patients as part of a project to introduce them to CQI. These results are presented as an example of this new direction. PMID- 8450690 TI - Examining issues in health care delivery for asthma. Background and workshop overview. AB - There have been recent increases in asthma prevalence, morbidity, and mortality in the United States. There is substantial evidence that problems in health care delivery may be contributing to these recent trends. Because of these recent changes, a reduction in asthma-related morbidity has been identified as a new national health objective for the year 2000. This article reviews some of the key aspects of patterns of asthma care in the United States, presents an overview of issues that may play a prominent role in the delivery of care, and provides an overview of the organization of the workshop. PMID- 8450692 TI - [Dyslipemia and HIV-1 infection in intravenous drug addicts]. AB - BACKGROUND: It has been demonstrated that hypertriglyceridemia and hypocholesterolemia are frequent signs in homosexual patients with AIDS. Lipid abnormalities of the intravenous drug addict (IVDA) however, and its relation with infection by the human immunodeficiency virus (HIV) have not been sufficiently studied. METHODS: Four hundred thirty-five consecutive patients attended for infectious complications or for carrying out detoxication treatment were studied. Demographic (age, sex), anthropometric (weight, height), use of intravenous drugs (principal drug used, time of addiction) and analytic data (HIV 1 antibodies, total lymphocytes, CD4+ lymphocytes, serum albumin, total cholesterol, plasma triglycerides and transferrinemia) were collected. RESULTS: The age of the patients was found to be between 15-44 years of age. Ninety-five percent were heroin addicts with a time of addiction greater than 4 years. Those who were HIV-1 positive had been drug users for a longer period of time (p < 0.01), had less weight (p < 0.01), lower albuminemia (p < 0.05) and cholesterolemia (p < 0.01), as well as a lower number of CD4+ lymphocytes (p < 0.01). No differences were observed with regard to age, transferrinemia and plasma triglyceride concentration. The prevalence of hypertriglyceridemia (> 1.97 mmol/l; 175 mg/dl) was of 18% for the IVDA with HIV-1 infection and 23% for seronegative individuals (p = 0.3). Hypercholesterolemia was significantly more prevalent in HIV-1 positive individuals (20%) than in the seronegative subjects (9%) (p < 0.01). In the HIV-1 positive patients, most of whom where asymptomatic, a decrease in total cholesterol and an increase in plasma triglycerides was observed according to the decrease in the number of CD4+ lymphocytes. CONCLUSIONS: Infection by the human immunodeficiency virus is accompanied by an increase in plasma triglycerides and a decrease of total cholesterol in relation with the alteration of cellular immunity. However, heroin addicts present some differential characteristics similar to those of chronic alcoholics, poor diet, anorexia induced by opioids, autoimmunity phenomena and recurrent infections throughout drug addiction which may justify lipid abnormalities of multifactorial origin. PMID- 8450693 TI - [Prevalence of human immunodeficiency virus infection among parenteral drug users in the community of Valencia 1987-1991)]. AB - BACKGROUND: To contribute to the knowledge of the frequency and distribution of infection by the HIV-1 in intravenous drug consumers (IVDC) the prevalence of infection in those in whom the voluntary serologic testing was practised and tendency over 5 years were studied. METHODS: The study included 2794 IVDC from centers of primary health care (70%) or those who attended directly (30%), from 1987 to 1991, to three Centers of Information and Prevention of AIDS located in the cities of Valencia, Alicante and Castellon in which the voluntary and free practice of the test of antibodies versus HIV-1 was performed. The serologic test (enzymoimmunoassay) was carried out in 2694 individuals whose positive results were confirmed by Western-blot. Risk factors of the infection in addition to sociodemographic data were collected by questionnaire. RESULTS: The estimated global prevalence was of 49.9% with confidence intervals of 95% (CI 95%) of 48.1% to 51.7%. Differences were observed according to the city with the highest being Valencia (55.3%, CI 95%: 52.8%; 57.8%) in comparison with Alicante (43.7%. CI 95%: 40.5%; 46.9%) and Castellon (41.3%, CI 95%: 35.6%, 47%). A decrease in prevalence was detected during the period studied (chi 2 of tendency = 6.37; p = 0.011), with this decrease only being produced in Alicante and Castellon. No differences were found with regard to sex in contrast to those found according to age, from 35.3% in those under 20 years of age to 59.5% in those over 29 years (chi 2 of tendency = 80.62; p < 0.0001). Only in the youngest age groups was a decreased tendency in prevalence found. The IVDC attended reported interchanging of needles at the time of consultation in 16.9% (CI 95%: 15.5%; 18.3%) with a descending temporal tendency from 27.7% in 1987 to 2.8% in 1991 (chi 2 of tendency = 14.18; p = 0.0001). Only 18.7% (CI 95%: 17.2%; 20.2%) of the IVDC used condoms in more than 66% of their sexual encounters of vaginal coitus. No differences were found with respect to sex or year of consultation. CONCLUSIONS: The prevalence of infection by the HIV-1 in intravenous drug consumers requesting the serologic test is decreasing in the Community of Valencia. This reduction in frequency should be confirmed by estimated rate of incidence of seroconversion. The frequency of the use of condoms in intravenous drug consumers is low conditioning a high risk of extension of the epidemics by sexual transmission. PMID- 8450694 TI - [Prevalence of anti-Leishmania antibodies in parenteral drug addicts. Yield value of 2 study techniques]. AB - BACKGROUND: The prevalence of antibodies anti-Leishmania in intravenous drug addict (IVDA) patients suspect of visceral leishmaniasis (VL) and the diagnostic profitability of two tests for detecting anti-Leishmania antibodies were studied. METHODS: Serum samples corresponding to 91 healthy non IVDA individuals (group 1), 143 IVDA individuals attended in consultation for febrile illness and lymph node enlargement (group 2) with only one serum determination, and 42 IVDA individuals in whom sequential serologic study (group 3) was performed were analyzed. IgG and IgM antibodies were studied by indirect immunofluorescence (IIF). The individuals of group 1 and 90 of those of group 2 (45 with anti Leishmania IgG antibodies and 45 without by IIF) were simultaneously studied by ELISA to analyze IgG antibodies. RESULTS: No antibodies were detected in subjects from group 1 with the two techniques used. In group 2 IgG were detected in 43.3% of the patients (titer distribution: 46.8% at 1/32, 32.3% at 1/64 and > 1/64 in 21%). In group 3 seroconversion of IgG was found in 18 cases. In 6 patients IgM was observed: 3 from group 2 (with low titers of IgG) and the remaining pertained to group 3 being accompanied by seroconversion of specific IgG. In the remaining 15 patients of group 3 seroconversion of IgG did not accompany positive IgM. No association was found in the results obtained by IIF and ELISA (p = 0.3; chi 2). CONCLUSIONS: It was found that indirect immunofluorescence and ELISA techniques are complementary methods in the indirect diagnosis of visceral leishmaniasis overall in the population of intravenous drug addicts. In this population acute disease may be manifested by IgG seroconversion with or without positive IgM although IgG seroconversion seems to be a more useful criteria given the greater number of patients in whom it is presented in this form. The high frequency of antileishmania antibodies in intravenous drug addict patients in Spain is of note. PMID- 8450696 TI - [Vertigo: have we made a progress in its diagnosis?]. PMID- 8450695 TI - [Mycobacterium avium-intracellulare disseminated infection in patients with AIDS]. AB - BACKGROUND: Disseminated infection by Mycobacterium avium-intracellulare is almost exclusively produced in individuals with HIV infection. The incidence of this infection in Spain is unknown. METHODS: The clinical and microbiologic registries of 30 patients with AIDS and disseminated infection by Mycobacterium avium are reviewed. METHODS: Twenty-three percent of the patients with AIDS had, at some time in their evolution, disseminated infection by M. avium. The clinical picture included prolonged fever, digestive symptoms, weight loss and appearance of lymph node enlargement. This infection appeared in patients with severe alteration of cellular immunity (mean CD4 lymphocytes: 0.19 x 10(9)/l). Although medium term prognosis was bad the causes of death of the patients were other opportunistic diseases related with the immunodeficiency. CONCLUSIONS: Infection by Mycobacterium avium is frequent among the population of individuals with HIV infection. With the appearance of prolonged fever in a patient with HIV infection and CD4 lymphocyte count lower than 0.2 x 10(9)/1 appropriate microbiologic studies including blood cultures for mycobacteria should be initiated. PMID- 8450697 TI - [Epidemic Kaposi's sarcoma in women: presentation of 4 cases]. AB - Epidemic Kaposi's sarcoma is the neoplasm most frequently manifested in infection by the human immunodeficiency virus. Its prevalence is considerably higher among homosexual males than among intravenous drug users with practically exclusive infection in this sex. Four cases of Kaposi's sarcoma in women with the human immunodeficiency virus are described. Two of these subjects were intravenous drug users and the other two were heterosexually promiscuous as the only conduct of risk for acquiring infection by the human immunodeficiency virus. Kaposi's sarcoma was the form of presentation of the syndrome of acquired immunodeficiency syndrome in these four patients. PMID- 8450698 TI - [Retroviruses and autoimmune diseases]. PMID- 8450699 TI - [Clinical course of HIV infection/AIDS in developed countries. Impact on tuberculosis]. PMID- 8450700 TI - [Specific radiologic signs in mitochondrial encephalomyopathy syndrome with lactic acidosis and cerebral ischemia]. PMID- 8450701 TI - [The use of topical non-steroidal anti-inflammatory agents in elderly patients taking oral anticoagulation agents]. PMID- 8450702 TI - [Subcutaneous abscess caused by Nocardia asteroides in a renal transplant recipient]. PMID- 8450703 TI - [The quality of compliance of case record forms in clinical trials]. PMID- 8450704 TI - Morphine physical dependence in the hibernator: central nervous system mechanisms underlying the development of dependence remain functional during depression induced by pentobarbital anesthesia. AB - Earlier work suggested that adaptive mechanisms of the hibernating brain may also block the development of morphine physical dependence. To test an alternate view that CNS depression itself might be the major factor in the failure of dependence to develop, we compared the strength of dependence produced by morphine (two 75 mg pellets, s.c.) given for 12 hr in the presence, versus in the absence, of continuous pentobarbital anesthesia in nonhibernating ground squirrels (Citellus lateralis) and, in addition, in rats. Dependence was measured by the naloxone (5 mg/kg, s.c.) evoked abstinence syndrome in the awake state. The results demonstrated that pentobarbital-induced general anesthesia does not significantly reduce the development of morphine dependence in either species. We conclude that CNS depression alone does not account for the hibernation-related reduction in morphine physical dependence. PMID- 8450705 TI - Inhibition of DFMO-induced audiogenic seizures by chlordiazepoxide. AB - Mice given 1% alpha-difluoromethylornithine (DFMO) in the drinking water for 5 weeks developed a hyperactive behavior characterized by uncontrolled running upon stimulation with noise. The running was followed by seizures and sometimes death. These behaviors are characteristic of audiogenic seizures. Strain differences in susceptibility to DFMO-induced audiogenic seizures were observed. The order of sensitivity to this DFMO effect was: C3HeB/FEJ = C3H/HeN > CBA/J = BALB/c. Chronic DFMO treatment was found to deplete whole brain putrescine and spermidine, but not spermine nor gamma-aminobutyric acid (GABA), in the 2 strains of mice analyzed, C3H/HeN and BALB/c. The audiogenic seizures were eliminated by pretreatment with the benzodiazepine, chlordiazepoxide (Librium) (40 mg/kg, ip) 105 minutes prior to testing for seizures. PMID- 8450706 TI - Inhibition of the aldosterone-suppressant activity of atrial natriuretic factor by progesterone and pregnancy in rats. AB - Angiotensin II (AII) caused concentration-dependent increase in aldosterone secretion by dispersed zona glomerulosa cells from non-ovariectomized (non-OVX) and ovariectomized (OVX) rats treated with the vehicle (peanut oil), beta estradiol (0.1 mg/kg/d x 3) or progesterone (2 mg/kg/d x 3); this effect of AII was greater on cells from progesterone- than from estrogen-treated animals. In contrast, atrial natriuretic factor (ANF) was 100- to 1,000-fold less effective in suppressing AII-stimulated aldosterone production by cells from progesterone treated (both non-OVX and OVX) and pregnant (17-20 day) rats than by cells from nonpregnant controls and estrogen-treated animals. To our knowledge, this is the first demonstration of an inhibition of an important action of ANF by another hormone and our data suggest that increased circulating levels of progesterone during pregnancy produce a relative refractoriness to the aldosterone-suppressant activity of ANF, which favors fluid/salt expansion. PMID- 8450707 TI - Inhibition of naloxone-precipitated withdrawal jumping by i.c.v. and i.t. administration of saline in morphine-dependent mice. AB - In morphine-dependent mice, s.c. and i.t. administered naloxone produced withdrawal jumping (ED50 values were i.t. = s.c.) but i.c.v. administered naloxone failed to produce dose-dependent jumping. Peak times of jumping were earliest after i.t. administration of naloxone among the three administration routes. These results suggested that the spinal site was more sensitive to naloxone than the supraspinal site. Concomitant administration of naloxone i.c.v. and i.t. did not precipitate jumping. It was found that i.c.v. and i.t. injections of saline inhibited withdrawal jumping precipitated by s.c. administered naloxone and that the i.c.v. effect was more profound than the i.t. effect. I.c.v. injection of saline also delayed the peak time of withdrawal jumping precipitated by s.c. administered naloxone. These inhibitory effects of the injection procedures may explain the difficulty of i.c.v. administered naloxone and concomitant i.c.v. + i.t. administered naloxone to precipitate jumping, and may explain the difference in the ED50 values of naloxone and the time courses of jumping. PMID- 8450708 TI - A physiological role of epidermal growth factor in cell kinetics of gastric epithelium. AB - Administration of epidermal growth factor (EGF) stimulates DNA synthesis in gut epithelial cells and inhibits gastric acid secretion. A physiological role of EGF in cell kinetics of gastric epithelium, however, has not been fully understood. In mature male mice, large amounts of EGF are produced in the submandibular glands, and sialoadenectomy (removal of the submandibular glands) causes a marked reduction of plasma EGF levels. For the evaluation of a biophysical function of EGF, sialoadenectomized mice and sham-operated mice were injected with 3H thymidine to compare the proliferative activity and the cell-turnover of gastric epithelium between the two groups using the autoradiographic analysis. When mice were killed 90 min after a single injection of 3H-thymidine, the percentages of fundic gland mucosal cells radiolabeled in sialoadenectomized and sham-operated mice were 27.3 +/- 5.0% and 26.3 +/- 5.8% (mean +/- SD), respectively. The difference was not significant (p > 0.05). Similarly, the labeling indices of pyloric gland mucosal cells were not different between the two groups (26.7 +/- 4.3% vs 27.8 +/- 3.7%, p > 0.05). In contrast, when mice were given 17 repeated injections of 3H-thymidine at 6 hr intervals and killed 48 hr after the last injection, labeling indices in sialoadenectomized mice were significantly lower than those in sham-operated mice (35.3 +/- 4.3% vs 52.8 +/- 1.1% in the fundic gland area; 41.0 +/- 6.2% vs 55.1 +/- 5.9% in the pyloric gland area, p < 0.001, respectively). Treatment of sialoadenectomized mice with EGF (5 mg/mouse per day) completely restored the percentages of the radiolabeled cells to control levels. These findings suggest that endogenous EGF plays a major role in maintaining biological cell-turnover of the mouse gastric epithelium. PMID- 8450709 TI - Differential effects of methimazole and dexamethasone in avian muscular dystrophy. AB - We showed previously that thyroid antagonists and glucocorticoids partially alleviated the impaired righting ability and abnormally high levels of plasma creatine kinase activity in genetically dystrophic chicks. The goals of the present study were: (1) to ascertain whether the beneficial effects of methimazole (MMI; thyroid antagonist) on muscle function and plasma creatine kinase (CK) activity in dystrophic chickens are correlated with significant reduction in plasma triiodothyronine (T3) and thyroxine (T4); (2) to assess whether the MMI-induced thyroid changes are accompanied by increased plasma corticosterone level and/or changes in muscle glucocorticoid receptors which might account partially for the beneficial effects of MMI; and (3) to determine if plasma T3 and T4 are reduced in dexamethasone (DEX) treated dystrophic chickens which might account at least partially for the beneficial effects of DEX (a potent glucocorticoid) on avian dystrophy. The data show that beneficial effects of MMI are associated with reduced plasma levels of thyroid hormones and increased circulating levels of corticosterone. In addition, DEX actually increases plasma T3 levels. These differential effects indicate that reduced plasma thyroid hormone levels do not represent a common mechanism of beneficial drug effects in avian muscular dystrophy. On the other hand, elevated plasma glucocorticoid levels accompany the beneficial effects of both severe hypothyroidism and DEX treatment. The data also show that MMI induces down regulation of muscle cytosolic glucocorticoid receptors which are higher than normal in dystrophic muscles. PMID- 8450710 TI - Excretion of urinary epidermal growth factor in non-insulin dependent diabetes mellitus. AB - Morning urine samples were assayed for human EGF (hEGF) in 137 non-insulin dependent diabetic patients with normal serum creatinine and beta 2-microglobulin levels. Serving as controls, 80 age- and sex-matched healthy subjects were also examined. A significant positive correlation between hEGF excretion and the level of hemoglobin A1C (HbA1c) was present in those patients with a HbA1c value exceeding 8% (r = 0.37; p = 0.003) but not in the overall patients. The urinary hEGF level did not correlate with the concentration of glucose in urine or plasma. The mean urinary hEGF level of diabetic patients was significantly lower than that of healthy subjects. The mean urinary hEGF level was significantly lower in the patients with a diabetic history that exceeded five years as compared with those with a history below five years. The mean urinary hEGF level was significantly lower in the patients with retinopathy vs. those without retinopathy. In the patients with HbA1c value below 8%, the mean urinary hEGF level was lower in the patients whose urinary albumin level exceeded 1.7 mg/mmol.creatinine as compared with those whose urinary albumin excretion was below 1.7 mg/mmol.creatinine. These findings suggest that urinary hEGF excretion may decrease with the progression of diabetic complications in the patients with well-controlled glycemia, and that inadequate glycemic control may lead to an increased excretion of urinary hEGF in the early disease stage. PMID- 8450711 TI - Chronic stress induced changes in LH secretion: the contribution of anorexia associated to stress. AB - The effects of chronic intermittent immobilization (IMO) on serum LH levels of adult male rats were studied. Chronic IMO (2 h daily for 13 days) did not alter basal LH levels, but abolished the LH response to acute stressors (IMO and tailshock). The inhibition of LH caused by acute exposure to IMO for 4 or 18 h was similar in control and chronic IMO rats. Also the LH response to exogenous LHRH administration was normal in chronically stressed rats. When a group of rats eating the same amount of food as that eaten by immobilized rats was introduced (pair-fed), an inhibition of LH response to acute stressors quite similar to that found in chronic IMO rats was observed. These data indicate that chronic stress induced inhibition of LH release caused by short-term exposure to acute stressors was located above the pituitary and was mainly due to anorexia accompanying daily exposure to the stressor. PMID- 8450712 TI - Detection and partial characterization of an anti-steroidogenic peptide from the humoral immune system of the chicken. AB - Phenomenological association of alterations of immune system function at the time of puberty (e.g. involution of the chicken bursa of Fabricius) has led to postulation that the humoral immune system may negatively affect the hypothalamo adenohypophyseal-gonadal axis of the neonate. Presently, we examined the effect of an acidic aqueous bursa of Fabricius extract, derived from prepubescent chickens, on in vitro basal and LH-stimulated progesterone biosynthesis by isolated ovarian granulosa cells of the largest preovulatory chicken follicles (F1 and F2). Crude extracts of < 5kDa and > 3kDa inhibited LH-stimulated progesterone secretion (P < 0.05). The bioactive component was observed to be heat labile and is sensitive to the endopeptidases chymotrypsin, trypsin and papain. The peptide is not sensitive to the exopeptidase, aminopeptidase M. Partial purification by reversed phase HPLC resulted in a fraction capable of inhibiting in vitro steroidogenesis. This fraction suppressed LH-stimulated progesterone biosynthesis to approximately basal levels (79% suppression). Following removal of the peptide, granulosa cells were capable of LH-stimulated progesterone biosynthesis similar to control cells. Bursal extract significantly inhibited cAMP analog-stimulated progesterone biosynthesis. These data indicate that the anti-steroidogenic peptide derived from the chicken bursa of Fabricius is a single heat labile, amino terminally blocked peptide with bioactivity independent of the gonadotropin receptor of the granulosa cell. PMID- 8450713 TI - Amino acid composition and N-terminal sequence of purified cystine binding protein of Escherichia coli. AB - Cystine Binding Protein (CBP), a commercially available crude protein extract obtained by osmotic shock of Escherichia coli (E. coli), was studied to characterize further its cystine binding properties and to elucidate its cystine transport activity. We report here the amino acid composition, the N-terminal amino acid sequence analysis and some binding characteristics of the purified cystine binding component of CBP. A search of the Swiss-Prot version 20 data base revealed that this sequence is unique. PMID- 8450714 TI - Characterization of vasopressin-mediated GSH efflux from Hep G2 cells: significance of protein kinase C. AB - Vasopressin stimulated GSH efflux from Hep G2 cells. The maximal effect was observed at 10nM. Pretreatment with pertussis toxin or cholera toxin for 18 hr increased GSH efflux. Vasopressin-mediated GSH efflux was observed even in the cells pretreated with those compounds. Dibutyryl-cAMP or dibutyryl-cGMP enhanced GSH efflux although an additive effect of vasopressin was not observed. Glucagon and a phorbol ester independently increased GSH efflux while both compounds decreased the effect of vasopressin. Staurosporine, an inhibitor of protein kinase C, inhibited vasopressin-mediated GSH efflux. The effect of vasopressin was observed even in the absence of extracellular Ca2+. Vasopressin stimulates GSH efflux from Hep G2 cells and protein kinase C-dependent pathway may play a significant role in vasopressin-mediated GSH efflux. PMID- 8450715 TI - Calcium dependent magnesium uptake in myocardium. AB - The frog myocardium maintains magnesium content at a steady state level when stimulated at 0.4Hz while being perfused with Ringer's solution containing 1 x 10(-3) M Ca2+ and 5 x 10(-7) M magnesium. When calcium is removed 43% of tissue magnesium is lost within 30 seconds or 12 beats. Restoration of calcium to the perfusion solution causes reaccumulation of magnesium from a solution containing 5 x 10(-7) M magnesium. The reaccumulation of magnesium indicates a highly selective transport system for magnesium which is dependent upon the presence of calcium. Calcium appears to reduce the leak of magnesium from the myocardium and enhances the transport of magnesium into the myocardial cell. Intracellular magnesium is a necessary cofactor for hundreds of enzymes, and is essential for protein synthesis and as an extracellular divalent cation helps to stabilize excitable membranes in conjunction with calcium. The concentration of ionized magnesium in the sarcoplasm of myocardial muscle has an average value of 1.45 mM +/- 1.37 (standard deviation), N = 19) with a range of 0.5 to 3.6 mM (1). The heart with its numerous mitochondria and high enzymatic activity is vulnerable to myocardial damage due to magnesium loss. The isolated frog ventricle conserves intracellular magnesium when perfused with Ringer's solution containing no added magnesium and maintains function for hours. The ability to conserve magnesium suggests a low permeability of the sarcolemma to magnesium and an extremely efficient inward transport system. Removal of calcium as well as magnesium from the perfusion solution causes a rapid loss of tension in the electrically driven frog ventricle (0.4) Hz.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450716 TI - Tryptophan loading increases daytime serum melatonin levels in intact and pinealectomized rats. AB - L-tryptophan (L-Trp) effects on serum and pineal melatonin were studied in fasted and non-fasted rats. Oral administration of L-Trp during the day caused serum melatonin to increase 4-fold compared to that of saline treated rats; this occurred in both fasted and non-fasted animals. In the same animals, neither NAT, HIOMT, not melatonin levels were changed. In a second study, pinealectomized rats were loaded with L-Trp. In these animals, as in those that had an intact pineal gland, L-Trp loading caused a large increase in immunoreactive serum melatonin. The results suggest that the increased melatonin in serum due to L-Trp administration is primarily derived from an extrapineal organ. PMID- 8450717 TI - Enzymatic formation and electrochemical characterization of multiply substituted glutathione conjugates of hydroquinone. AB - 1,4-Benzoquinone can undergo redox cycling in the presence of glutathione to produce multiply substituted products. It has previously been shown that the nephrotoxicity of the hydroquinone-glutathione conjugates increases with increasing substitution. However, based on chromatographically-assisted hydrodynamic voltammetry (CA-HDV), the oxidation potential was shown to apparently increase which, should lead to decreased toxicity. From the chemical formation of multiply substituted hydroquinone-glutathione conjugates from benzoquinone and glutathione, it is clear that the thermodynamic oxidation potential must decrease as substitution increases. This was confirmed by cyclic voltammetric (CV) characterization of the isolated conjugates. The discrepancy between the CV and CA-HDV data apparently results from kinetic factors arising from differences in the treatment of the electrode surface between the two experiments. The multiply substituted hydroquinone-glutathione conjugates were also produced in horseradish peroxidase incubations containing hydroquinone and glutathione. These products were identified chromatographically, spectrophotometrically, and electrochemically. The increasing ease of oxidation and the possible enzymatic formation of multiply substituted hydroquinone glutathione conjugates indicates that this pathway may occur in vivo and contribute to the toxicity of quinones. PMID- 8450719 TI - False negative bone scan in a female runner. AB - Stress fractures are more prevalent in today's fitness cognizant society. Stress fractures of the femoral neck are common and present with specific symptoms and findings. The diagnosis is based on clinical history, physical exam, radiography, bone scintigraphy, and computed tomography (C.T.) scans. The triple-phase bone scan is the most sensitive test for the diagnosis of stress fractures and is considered the gold standard for the diagnosis of the occult stress fracture. This case presents a 42-yr-old female marathon runner who presented with hip pain and clinical symptoms indicating a stress fracture of the femoral neck. Initial radiographs and a triple-phase bone scan were negative. When symptoms persisted, a repeat x-ray revealed a femoral neck fracture of the superior surface. In spite of a false negative bone scan, clinical suspicion allowed appropriate treatment of this femoral neck stress fracture. Nondiagnosed stress fractures of the femoral neck may lead to severe disability, including avascular necrosis of the femoral head. Therefore, clinical index of suspicion is very important even if ancillary tests are nondiagnostic. PMID- 8450718 TI - Urinary excretion of immunoglobulins and their subunits in human subjects before and after exercise. AB - Immunoglobulins and their subunits in urines collected before and after exercise from healthy human subjects were studied. Quantitative analysis showed that only gamma A- and gamma G-immunoglobulins were excreted as whole molecules in normal urine, at a concentration of 0.35 and 1.70 micrograms/min., respectively. Exercise enhanced the excretion of both types of molecules. In some cases, gamma D-immunoglobulins were found in "exercise urine." Gel filtration on Sephadex G 150 showed that only gamma G-subunits were present in normal and in "exercise urine." The distribution of gamma G-subunits was not affected by exercise. The authors consider the importance of the present data in relation to renal physiology. PMID- 8450720 TI - Relationship of lactate and ventilatory thresholds in cardiac transplant patients. AB - The ventilatory threshold (VT) has been suggested as a method for determining exercise training intensity in cardiac transplant patients (CTPs). Since the VT has not been validated against the more accepted marker of the anaerobic threshold, the lactate threshold (LT), in CTPs, the purpose of this investigation was to compare the VT to the LT within, as well as between, CTPs and normal subjects (NLs). Ten male orthotopic CTPs and 10 age, size, and gender matched NLs were exercised to symptom-limited maximal levels following incremental treadmill protocols. The VT was determined using the V-slope method, and the LT was identified using the log-log transformation method. The NLs and significantly higher absolute levels of VO2 at both the VT (1298.6 +/- 78.5 vs 919.0 +/- 57.2 ml.min-1) and LT (1561.1 +/- 144.2 vs 921.6 +/- 47.6 ml.min-1) compared with the CTPs. However, there was no significant difference in the relative VO2 (% peak) between CTPs and NLs at the VT (57.2 +/- 3.0 vs 49.0 +/- 3.5%) or LT (58.2 +/- 3.3 vs 58.5 +/- 4.9%), respectively. Within groups there was no significant difference between the VT and LT for either CTPs (919.0 +/- 57.2 vs 921.6 +/- 47.6 ml.min-1 or NLs (1298.6 +/- 78.5 vs 1561.1 +/- 144.2 ml.min-1). From the results of this investigation it appears that the VT may be used as an indicator of LT in CTPs and is within a range acceptable for clinical application.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450721 TI - Epidemiology of injuries associated with physical training among young men in the army. AB - It is widely acknowledged that musculoskeletal injuries occur as a result of vigorous physical activity and exercise, but little quantitative documentation exists on the incidence of or risk factors for these injuries. This study was conducted to assess the incidence, types, and risk factors for training-related injuries among young men undergoing Army infantry basic training. Prior to training we evaluated 303 men (median age 19 yr), utilizing questionnaires and measurements of physical fitness. Subjects were followed over 12 wk of training. Physical training was documented on a daily basis, and injuries were ascertained by review of medical records for every trainee. We performed univariate and multivariate analyses of the data. Cumulative incidence of subjects with one or more lower extremity training-related injury was 37% (80% of all injuries). The most common injuries were muscle strains, sprains, and overuse knee conditions. A number of risk factors were identified, including: older age, smoking, previous injury (sprained ankles), low levels of previous occupational and physical activity, low frequency of running before entry into the Army, flexibility (both high and low), low physical fitness on entry, and unit training (high running mileage). PMID- 8450722 TI - Surveillance of serious recreational injuries: a capture-recapture approach. AB - Serious injury from sport and recreation is a leading cause of morbidity and mortality in the United States. Historically, occurrences of diseases with substantial public health impact have been monitored via surveillance systems in order to obtain information concerning the frequency with which the diseases occur. Surveillance leads to efforts that identify risk factors, and eventually, control measures to reduce the incidence of disease. Currently, the surveillance of sports injury represents only limited coverage in the U.S. It is important to begin discussions regarding approaches toward the development of surveillance of these injuries. Methods based upon the communicable disease surveillance model could potentially be used to monitor serious sports injuries. One method of surveillance, using the statistical approach of capture-mark-recapture, is presented as an example by which a national system of surveillance of serious sports injury could be established. PMID- 8450723 TI - Introduction: oxidant stress, aging, and exercise. AB - In recent years research in the basic and applied sciences has broadened our understanding of oxygen chemistry and its influences on biological systems. Although living organisms are endowed with a broad array of biochemical defense mechanisms for protection against potentially harmful radical chemistry, oxidative stress may overwhelm those defenses. It is now clear that exercise may initiate oxidative stress. It is the aim of this symposium to review and broaden our understanding of the problem of free radical chemistry as it applies to the exercise milieu. PMID- 8450724 TI - Influence of exercise on clearance of oxidant stress products and loosely bound iron. AB - The significance of free radical chemistry within the exercise and post-exercise milieu is not yet well understood. It is yet to be determined whether adequate biochemical defense mechanisms exist to protect the organism from oxygen-centered radicals generated by exercise. Rats trained at 70% VO2peak for 6 wk were compared with controls after an exhaustive run. Post-exhaustion urinary malondialdehyde, gastrocnemius loosely bound iron, and susceptibility to oxidant stress were assessed. Exhaustive exercise resulted in a significant (P < 0.05) increase in urinary malondialdehyde, tissue loosely bound iron, and susceptibility to oxidative stress in both control and trained rats. The untrained group's tissue iron and susceptibility to oxidative stress were both significantly greater than trained rats. Electrical stimulation of perfused hindquarters of untrained and trained rats resulted in a significant increase of malondialdehyde into the perfusate. Trained rats cleared the malondialdehyde from the perfusate more rapidly than did the untrained. PMID- 8450725 TI - Antioxidant enzyme response to exercise and aging. AB - Antioxidant enzymes play an important role in defending the cells against free radical-mediated oxidative damage. The present investigations, using rats as models, indicate that antioxidant enzyme systems undergo significant alteration during aging and in response to acute and chronic exercise. Hepatic and myocardial antioxidant enzymes show a general decline at older age, whereas activity of glutathione-related enzymes in the liver and mitochondrial enzymes in the heart increase significantly. Skeletal muscle antioxidant enzymes are uniformly elevated during aging. An acute bout of exercise can increase activity of certain antioxidant enzymes in various tissues. The mechanism for this activation is unclear. Exercise training has little effect on hepatic or myocardial enzyme systems but can cause adaptive responses in skeletal muscle antioxidant enzymes, particularly glutathione peroxidase. These findings suggest that both aging and exercise may impose an oxidative stress to the body. PMID- 8450726 TI - Antioxidants: role of supplementation to prevent exercise-induced oxidative stress. AB - Exercise of a sufficient intensity and duration has been shown to increase indicators of oxidative stress. Oxidative stress has been indicated in skeletal muscle, liver, blood, and in expired air samples as indicated by the by-products of lipid peroxidation. Antioxidants are known to reduce oxidative-radical-induced reactions. This paper presents information concerning the effects of exercise on vitamin E and C concentrations in several tissues. This paper also discusses the effects of supplementation of vitamin E and vitamin C on their ability to alter exercise-induced lipid peroxidation. This paper indicates that limited information is available concerning the effects of both vitamins on exercise induced oxidative stress. The viability of antioxidants alone and in conjunction with each other in preventing exercise-induced lipid peroxidation requires further investigation. PMID- 8450727 TI - Increased life expectancy of world class male athletes. AB - Reliable data are scanty on the incidence of chronic diseases and life expectancy (LE) of highly trained athletes. We therefore studied Finnish male world class athletes to estimate the LE of athletes. Finnish team members in the Olympic games, World or European championships or intercountry competitions during 1920 1965 in track and field athletics, cross-country skiing, soccer, ice hockey, basketball, boxing, wrestling, weight lifting, and shooting were included (N = 2613 men). The reference cohort, 1712 men, was selected from the Finnish Defence Forces conscription register matched on age and area of residence. All referents were classified completely healthy at the time of induction to military service. The stratified Kaplan-Meier product limit method and the Cox proportional hazards model were used to estimate the life expectancies and the mortality odds ratios (OR) and their confidence limits. The mean LE adjusted for occupational group, marital status, and the age at entry to the cohort (and its 95% confidence limits) was in endurance sports (long distance running and cross-country skiing) 75.6 (73.6, 77.5) yr; in team games (soccer, ice hockey, basketball, as well as jumpers and short-distance runners from track and field (73.9 (72.7, 75.1) yr; in power sports (boxing, wrestling, weight lifting, and throwers from field athletics) 71.5 (70.4, 72.2) yr; and in the reference group 69.9 (69.0, 70.9) yr. The increased mean life expectancies were mainly explained by decreased cardiovascular mortality (endurance sports mortality odds ratio OR = 0.49 (95% CL 0.26, 0.93), team sports OR = 0.61 (0.41, 0.92) compared with referents). For maximum life span no differences between the groups were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450728 TI - Influence of quadriceps conditioning on soleus motoneuron excitability in young and old adults. AB - In an effort to investigate neuromuscular changes with age, the isometric force time curve of the Achilles tendon-tap reflex (ATR) was measured in 10 college age (M = 20.9 yr) and 10 healthy active old subjects (M = 74.3 yr). In an effort to investigate spinal interneuronal pathways, the tendon-jerk was also conditioned with a tap to the ipsilateral or contralateral patellar tendon. The conditioning stimulus preceded the ATR by 25, 40, 55, 70, 85, 100, 115, 130, or 145 ms. Three trials were elicited at each conditioning interval plus three unilateral trials, for 30 trials per experimental session. Results indicated that the force production of the unilateral Achilles tendon-tap reflex was significantly reduced and the half-relaxation times were significantly lengthened in the old subjects. Moreover, ipsilateral conditioning produced short-latency facilitation and long latency inhibition to the triceps surae in young subjects, whereas the same conditioning produced only a delayed long-latency inhibition in the old subjects. Similarly, the contralateral conditioning produced short-latency facilitation in the young subjects, with no changes observed in the old subjects. It is concluded that unilateral Achilles tendon-tap responses are different for the two groups, and that the reflex recovery profiles for the two groups are different. Several neurophysiological mechanisms are proposed to contribute to these differences. PMID- 8450729 TI - Evaluation of moment-angle curves in isokinetic knee extension. AB - The purpose of this study was to challenge the notion that the relationship of moment of force to angular velocity, determined in isokinetic knee extension tests, reflects the force-velocity relationship of human knee extensors. For this purpose, maximum-effort isometric knee extension moments were collected at seven different knee joint angles, and maximum-effort isokinetic knee extension moments were measured as a function of knee joint angle at angular velocities of 30, 60, 120, and 210 degrees.s-1. For the isokinetic contractions two protocols were used with a different threshold moment, i.e., the minimum knee extension moment that had to be reached isometrically before knee extension was initiated. In one protocol (LTM, for low threshold moment) the threshold was set at 5% of the maximum isometric knee extension moment produced at the starting angle of 85 degrees (180 degrees being full knee extension), in the second protocol (HTM, for high threshold moment) it was set at 95% of this isometric moment. During all contractions, electromyograms were recorded from m. vastus medialis, m. vastus lateralis, m. rectus femoris, and m. biceps femoris. The EMG signals were rectified and smoothed to yield SREMG. Two hypotheses were specifically tested. The first was that the threshold moment does not affect knee extension moments in the middle of the range of motion. Between knee angles of 100 degrees and 145 degrees, no differences were found between moments produced in the HTM protocol and those produced in the LTM protocol. Thus, the first hypothesis was supported. The second hypothesis was that subjects achieve the same level of muscle excitation at different speeds.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450730 TI - Is running style and economy affected by wearing respiratory apparatus? AB - The purposes of this investigation were to compare selected gait parameters characteristic of running without respiratory apparatus on a treadmill (NOR) with those displayed while wearing a mouthpiece-breathing valve apparatus (MP) and while wearing a respiratory face mask (MASK), and to compare the running economy (RE) measured during MP with that measured during MASK. Seventeen male volunteers [age = 32 +/- 5 yr (mean +/- SD); mass = 72.4 +/- 9.0 kg] performed three treadmill runs in randomly assigned order. All runs were identical in terms of duration (10 min), speed [200 m. min-2 (7.5 mph)], and grade (0%). During the last minute of each run, RE was measured and coordinate data were collected for determination of mechanical variables. The mechanical analyses were limited to 12 subjects. Stride length, vertical oscillation of the center of mass, hip and ankle range of motion, and average internal mechanical power output were not different for NOR, MP, and MASK. Knee range of motion was significantly less (P < or = 0.05) during MP than during NOR and MASK, primarily due to a significant reduction in maximum knee flexion during nonsupport. MASK RE was not significantly different (P > 0.05) from MP RE. It was concluded that wearing MP or MASK generally does not affect running style of individuals running at comfortable, submaximal running speeds and that RE measured with MP is not different from that measured with MASK. PMID- 8450731 TI - Visual loss and performance in blind athletes. AB - We examined the relationship between visual loss and athletic performance and evaluated the visual classification system used in the 1988 United States Association of Blind Athletes (USABA) Summer Games. Athletes were asked about their age, sex, training, years of participation in organized competition, age at onset of blindness and were given an ophthalmologic exam that included Snellen acuity, contrast sensitivity, and visual fields. In the speed track events, visual class,* sex, age, hours of training, and years participating were found to have a positive correlation with performance. Visual class and sex were significant predictors of performance in the intermediate distance events; visual class was the only significant predictor of performance in the long distance events. Visual class, sex, age, and hours of training were correlated with performance in the track and field (throwing) events. Weightlifting performance was influenced by age and sex. The most consistent predictor of performance in the swimming events was the number of hours training per week. Our results indicate that the current classification system for visual loss is useful for grouping athletes for competition. PMID- 8450732 TI - Effects of aerobic training in adolescents with Down syndrome. AB - The purpose of this study was to evaluate the effects that aerobic training has on adolescents and young adults with Down syndrome. Fourteen individuals with Down syndrome (mean age = 17.7 yr) participated in a 10-wk walking/jogging exercise training study. A pre- and post-training walking treadmill test was performed to determine the following parameters: peak oxygen uptake (VO2, absolute and relative), minute ventilation (VE, l.min-1), heart rate HR, b.min 1), RER (VCO2/VO2), and time and grade to exhaustion. Following the pre-training evaluations, subjects were assigned to a control group (N = 4) or an exercise group (N = 10). The exercise group underwent a 10-wk walk/jog training program at a frequency of 3 times per week, for a duration of 30 min, and at an intensity of approximately 65-75% peak HR. Following training, both control and experimental groups showed no changes in peak VO2 (absolute and relative), VE, HR, and RER. The exercise group, however, did demonstrate a significant improvement in peak exercise time (and grade). Although the training program did not produce improvements in aerobic capacity, it did produce gains in walking capacity. It was concluded that the adolescents and young adults may not be able to improve their aerobic capacity when performing a walk/jog training program. PMID- 8450733 TI - The influence of high-intensity exercise training on the Wlim-Tlim relationship. AB - When exercise to exhaustion is performed using at least two different intensities, work to fatigue (Wlim) can be expressed as a linear function of time to fatigue (Tlim). Whereas the slope of this function is related to endurance ability, the y-intercept is associated with the potential to perform high intensity interval exercise. The purpose of the present investigation was to determine the influence of 8-wk intermittent high-intensity exercise training on the y-intercept derived from the Wlim-Tlim relationship. Eight healthy, untrained male students (19.1 +/- 0.6 yr) completed five 60-s bouts of maximal exercise on the cycle ergometer, three times a week, for 8 wk. Seven controls avoided regular activity for the same period. Prior to and immediately following the training period, the Wlim-Tlim relationship, VO2max, and total work completed in five 60-s exercise bouts on the cycle ergometer were determined. Correlational analysis established relationships between the y-intercept and total work accomplished in the interval test pre- (r = 0.90; P < 0.01; N = 15) and post-training (r = 0.92; P < 0.01; N = 15), confirming that the y-intercept is related to the ability to perform exercise of this nature. Moreover, the "anaerobic" energy yield, calculated from total work and oxygen consumed during the interval exercise, was also related to the y-intercept (r = 0.78; P < 0.01). Interval training significantly increased both the y-intercept (P = 0.0015) and total work accomplished in the interval test (P = 0.001), while the slope of the Wlim-Tlim relationship (critical power) remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450734 TI - Simultaneous derivation of clothing-specific heat exchange coefficients. AB - Clothing adds resistance to heat exchange between the wearer and the environment. If clothing-specific heat exchange coefficients are known, a combined rational/empirical approach can be used to describe thermal exchange between clothed humans and the environment. However, during exercise these coefficients- typically calculated using thermal manikins--change, primarily due to wetting of the fabric during intense sweating and body movement. A procedure is described that allows for the simultaneous determination of both total insulation (IT) and resistance to water vapor permeation (Re) on exercising clothed subjects without the need to directly measure skin water vapor pressure or continuously weigh the subjects. Two tests are performed by each subject in each clothing ensemble. In one test, ambient water vapor pressure (Pa) is systematically increased in stepwise fashion while dry-bulb temperature (Tdb) is held constant; in the second test protocol Pa is held constant while Tdb is increased. Heat exchange data are collected at the time at which core temperature is forced out of equilibrium by the environment (according to the assumption that heat production is balanced by heat loss immediately prior to this critical environmental limit). Previous studies using similar approaches have typically estimated IT a priori and used this value in the subsequent derivation of Re for each clothing ensemble or condition tested. In the proposed method, IT and Re are derived from the solution of two simultaneous equations based on heat balance data from both tests. This paper describes and critiques this methodology via an error analysis, and compares the coefficients obtained with those from similar trials using other physiological and nonphysiological approaches. PMID- 8450735 TI - Effect of bone density on body composition estimates in young adult black and white women. AB - Bone mineral content (BMC) and density (BMD) by dual x-ray absorptiometry, total body water (TBW) by the deuterium oxide (D2O) dilution technique, and body density (Bd) by hydrostatic weighing were measured in 26 black (B) and 26 white (W) young adult women. Both groups were similar in age, height, weight, and total skinfolds; however, black subjects had significantly higher BMC and BMD. Formulas to estimate percent body fat (%BF) from Bd included Siri's two-component equation for the reference man, which assumes a fat free body density (FFBd) of 1.100 g.ml 1, and an adjusted two-component formula that assumes a lower FFBd of 1.095 g.ml 1. Percent body fat was also predicted from TBW and by several multicomponent models that corrected for individual subject variation in measured BMC and TBW. The two groups did not differ significantly in %BF predictions by any of the methods. However, the difference in %BF between the groups was halved with the four-component model (B = 21.9%; W = 23.6%) as compared with that calculated from the Siri two-component densitometric model (B = 21.2%; W = 24.2%). Within each racial group, %BF was not significantly different when predicted by two-component or multicomponent models. However, %BF of individuals with the highest and lowest BMD was substantially under- and overpredicted, respectively, by Siri's equation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450737 TI - Sports anemia and iron supplements. PMID- 8450736 TI - Comparison of two methods for computing exogenous substrate oxidation using 13C labeling. AB - With 13C stable isotope as tracer, the purposes of this study were to measure the oxidation rates of exogenous glucose by using two computation procedures that take into account changes in isotopic composition of CO2 arising from oxidation of endogenous substrates (Rendo) and compare these results with studies using 14C glucose. Two different low levels of 13C-enrichment were used in the first procedure, while a very high level of enrichment was used in the second one. Each of the eight subjects completed four exercises (68 +/- 5% VO2max; 90 min) on cycle ergometer, at 7-d intervals. After 30 min of exercise, the subjects ingested in a single bolus of 30 g of 13C-glucose, dissolved in 300 ml of water, enriched at three different levels (trials A and B = -10.9 and +2.5; trial C = +291.9/1000 delta 13C-PDB-1), or water only. The metabolic and endocrine state at rest and its response to exercise with or without glucose ingestion were similar in the four trials, with the exception of FFA and glycerol, which were blunted by the ingestion of glucose. As expected, Rendo significantly increased from rest ( 22.7 +/- 0.7/1000 delta 13C-PDB-1) to the beginning of exercise without glucose ingestion (-21.2 +/- 0.5/1000 delta 13C-PDB-1). The amounts of exogenous glucose oxidized over the last hour of exercise and computed from trials A and B and from trial C were 14.9 +/- 4.4 and 13.0 +/- 4.2 g, representing 7.4 and 6.3% of the total energy requirement, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450738 TI - In vivo oxygen tension and temperature: simultaneous determination using 19F NMR spectroscopy of perfluorocarbon. AB - A novel technique is presented to measure in vivo simultaneously oxygen tension and temperature using 19F NMR spectroscopy of perfluorocarbon. This work examines the variation with oxygen tension (pO2) and temperature of the individual spin lattice relaxation rates (R1) of the 19F resonances of the perfluorocarbon emulsion Oxypherol-ET. A linear relationship between R1 and pO2 is confirmed for all the resonances at any specific temperature in the range 27-50 degrees C. Similarly, a linear relationship is determined between R1 and temperature at any specific pO2 in this temperature range. Each resonance behaves uniquely with respect to temperature and pO2 and consideration of 2 or more resonances uniquely defines pO2 and temperature simultaneously, and unambiguously. This concept is demonstrated in vivo in a murine tumor and perfused rat heart, where pO2 and temperature were both determined without prior knowledge. PMID- 8450739 TI - Assessment of changes in murine tumor oxygenation in response to nicotinamide using 19F NMR relaxometry of a perfluorocarbon emulsion. AB - The oxygen dependencies of the 19F NMR spin-lattice relaxation rates (R1 = 1/T1) of a perfluorocarbon emulsion sequestered in a murine tumor model has been used to evaluate nicotinamide, a radiosensitizer believed to act through enhanced tissue oxygenation. Fluorine-19 NMR spectroscopic measurements from solid Radiation-Induced Fibrosarcoma (RIF-1) tumors in C3H mice showed a statistically significant improvement in tumor pO2 for a Nicotinamide-treated group, with a delta pO2 = 4.7 +/- 3 torr ( = mm Hg) (Mean +/- SEM) at t = 60 min (P < .01), and 4.5 +/- 3 at t = 70 min post intraperitoneal injection (P < 0.02) as compared with saline-treated Controls, while several other time points for which t > 30 min were significant at the P < 0.05 level. Both groups had n = 10, and the statistics were based on Student's one-tailed group t test. By comparison, in another study group where breathing gas was switched from air to 100% O2, a statistically insignificant increase of 2 torr was realized in tumor pO2 (n = 9). The maximal treatment effect occurs at a delay of 60 to 70 min, consistent with results obtained by other investigators using radiobiology techniques. Fluorine 19 spectroscopic relaxometry can measure therapeutically meaningful changes in in vivo tumor pO2 and represents an improvement in expenditures of time, animal resources, and statistical power over conventional radiobiological methods. PMID- 8450740 TI - Metabolic changes in activated T cells: an NMR study of human peripheral blood lymphocytes. AB - Using NMR spectroscopy, we studied purified, human T lymphocytes in a serum-free medium. Purified cells were entrapped inside agarose beads and induced to proliferate by the mitogens phorbol-12-myristate-13-acetate and ionomycin. T lymphocytes in standard culture and inside agarose beads exhibit comparable viability, and similar extent and kinetics of DNA synthesis and interleukin-2 secretion. 31P-NMR revealed decreased phosphomonoester and increased phosphodiester content in cells stimulated for two days or longer. 13C-glucose utilization and 13C-lactate production rates showed that 85% of the utilized glucose was converted to lactate. 1H-NMR spectra of the perfusing media indicated that lactate was also produced from substrates other than glucose or glycogen. Glucose accounted for 25% of the lactate produced by quiescent cells, and for 67% of lactate production by stimulated cells. Glycolysis was enhanced 6-fold within the first 2 hours following stimulation, and 15-fold by 48 or 96 h. Aerobic lactate production was increased 3-fold by 48 h, with only a minor enhancement during the first 12 h of stimulation. Our results indicate a shift from mostly aerobic to mostly anaerobic lactate production in T lymphocytes within the first 90 min of the G0 to G1 transition during cell cycle progression. PMID- 8450741 TI - Correction of translational motion artifacts in multi-slice spin-echo imaging using self-calibration. AB - In this paper, we describe a method for detecting and correcting in-plane bulk translational motion in multislice spin-echo imaging using self-calibration and postprocessing. A constant phase encoding offset between slices is used to evenly spread out the low spatial frequency echoes to allow accurate motion detection by self-calibration. Motion detection in both x and y directions is achieved by interchanging the readout and phase encoding directions for the alternate slices. Displacements are determined by cross correlating the modulus of each 1D transformed echo with a reference box car function whose width equals that of the imaged object. In addition, phase errors induced by the velocity in the readout direction are estimated and corrected using the displacement data. The results obtained from knee studies at 0.5 T and 1.5 T show that the artifacts due to translational motions are significantly suppressed upon correction. The method does not require any additional pulses or time, and the data processing can be easily implemented. PMID- 8450743 TI - Consistent projection reconstruction (CPR) techniques for MRI. AB - Motion of the subject causes inconsistencies in MR scan data which in turn produce streaks in projection reconstruction (PR) scans or ghosts in 2DFT imaging. It is shown that a data manifold consistent with a static object may be extracted from input scan data by applying consistency criteria based on moment or Fourier expansions of the object's projections. The criteria limit the spectrum of azimuthal variation relative to the radial moments or radial spectral components, and their application diminishes k-space inconsistencies from motion or flow by discarding unallowed expansion terms. This consistent projection reconstruction (CPR) algorithm was applied to the reconstruction of projection data from a moving phantom and from human abdominal sections, and in each case provided reduced motion streaks relative to conventional reconstructions. In addition, CPR was found to be effective when used with 2DFT data by resampling the Cartesian data as radial projections, but to a lesser extent. PMID- 8450742 TI - In vivo NMR imaging and spectroscopic investigation of renal pathology in lean and obese rat kidneys. AB - Diabetic nephropathy is a major cause of end-stage renal failure. While our understanding of the pathogenesis of nephropathy is incomplete, progressive glomerular injury appears to play a significant role in the decline of renal function. Proton NMR spectroscopy and imaging techniques were used to address changes in renal pathology associated with glomerular mesangial expansion in vivo in kidneys from spontaneously obese and lean (control) littermate Zucker rats. Fully functioning rat kidneys were surgically exposed and externalized for direct NMR signal detection via a coil placed around the organ. High-resolution (78 microns in plane) proton images were obtained at 4.7 T magnetic field strength revealing fine structure within the well-defined cortical and medullary regions. The obese rat kidney images were distinct in appearance from the lean kidney images and exhibited marked cortical expansion as well as increased overall kidney size. Enlargement of mean glomerular diameter was verified histologically in the obese kidneys as compared with the lean kidneys. Proton T1 and T2 relaxation times were determined from the entire kidney using standard spectroscopic techniques, and from specific regions within the kidney from multiple T1- and T-2 weighted images. Additionally, image contrast enhancement resulting from saturation transfer between protons in restricted-mobility environments and mobile water protons within the kidney was investigated in the lean and obese rat kidneys using magnetization-transfer imaging techniques. At the early stage of renal injury examined in this study, diseased and healthy kidneys could not be differentiated on the basis of relaxation times alone. The magnitude of saturation transfer obtained in cortical tissue in the lean and obese kidneys was also not statistically significantly different. However, the magnitude of saturation transfer achieved in the medullary tissue of obese kidneys was statistically significantly less than that achieved in lean kidneys. PMID- 8450744 TI - Classification of trabecular structure in magnetic resonance images based on morphological granulometries. AB - A new method of detecting structured changes in trabecular bone, such as those associated with osteoporosis, was evaluated on magnetic resonance images of the wrist. The method was based on gray-scale morphological granulometries which classify image texture by iteratively filtering an image and measuring the rate of change of structural diminution in a filtered-image sequence. A classification scheme capable of distinguishing structural changes in trabecular bone starting from normal trabeculae through sclerotic, cystic, and grossly porotic bone is presented. Results of the application of this technique to the evaluation of high resolution magnetic resonance images of the wrist are presented. PMID- 8450745 TI - Simultaneous temperature and regional blood volume measurements in human muscle using an MRI fast diffusion technique. AB - The thermal dependence of the translational diffusion coefficient and of the regional blood volume was investigated in vivo by using a special MR pulsed gradient technique with reduced sensitivity to bulk tissue motion. Measurements were done at 0.5 T, using a small gradient insert. The diffusion coefficient of muscle water was calibrated against thermocouple-measured temperature in vitro, both with the muscle fibers parallel and perpendicular to the diffusion gradient. The maximum muscle temperature variation obtained by percutaneous conduction was 8.8 +/- 1.6 degrees C under cooling and +3.7 +/- 1.6 degrees C under heating, from basal state. Simultaneously the fractional regional blood volume decreased by a factor of 3.5 under cooling and increased by a factor of 2.7 under heating. Due to the interdependence of microcirculation and tissue temperature, this technique may be used to follow heat production or deposition in living tissue (muscle exercise, electromagnetic irradiation, etc.). PMID- 8450746 TI - Dissecting and implementing STEAM spectroscopy. AB - A rapid, simple method for constructing a site-specific STEAM sequence from a basic Hahn three-pulse sequence is presented. The method assures maximum signal available from the hardware. PMID- 8450747 TI - The visualization of RF probe electric fields. AB - An assembly of resistive paper and liquid crystal sheet, conveniently and cheaply constructed for visual detection of the electric fields associated with an rf probe, is presented. Electrical asymmetries, and "hot-spots" usually associated with conservative electric fields, are easily visualized by the color patterns displayed. The device is of considerable assistance in probe design and the minimization of dielectric loss. PMID- 8450749 TI - Multi-turn, printed surface coil inductance, and Q optimization. AB - Wheeler's empirical inductance formula for a multi-turn, close-wound flat coil shows that the maximum inductance for a given length of wire occurs when the outer to inner radius ratios is equal to 15/7. A similar expression is proposed for a flat, printed spiral for surface coil antenna design by modifying one of the coefficients in Wheeler's formula. Measured inductance is in good agreement with this new formula and the optimum radius ratio for maximum inductance or Q is now of the order of 9/5. PMID- 8450748 TI - Changes in double quantum filtered sodium intensity during prolonged ischemia in the isolated perfused heart. AB - Intracellular sodium (Nai) concentrations rose immediately and progressively during ischemia in the isolated heart. The intracellular double quantum filtered sodium coherence (DQ) intensity also increased during ischemia. However, when normalized for Nai, the DQ intensity began to fall after 40 min of ischemia, and remained depressed during reperfusion. PMID- 8450750 TI - A cylindrically symmetric magnetic shield for a large-bore 3.0 Tesla magnet. AB - A 3.0 Tesla, 0.80-m bore magnet replaced our previous 1.9 Tesla, 0.76-m magnet. The 3.0 Tesla replacement magnet had a dipole moment of 1.7 with respect to that of the 1.9 Tesla magnet. The pre-existing cylindrically symmetric passive steel shielding was modified to confine the fringe fields of the replacement magnet to match those of the previous magnet. A cylindrically symmetric inner shield insert of about 20,000 kg was designed, fabricated, and installed. Upon energization of the magnet, the combined shielding met all design criteria. Alternative designs, optimization of cylindrically symmetric designs, and costs of fabrication, are presented herein. PMID- 8450751 TI - Elimination of susceptibility distortions and reduction of diffusion attenuation in NMR microscopy by line-narrowed 2DFT. AB - NMR imaging at high field strengths is adversely affected by magnetic susceptibility variations within the specimen. This is especially true in NMR microscopy. We present results using a line-narrowed imaging sequence which overcomes the image distortions associated with the frequency encoded readout method. Signal attenuation due to diffusion in static magnetic field gradients is also reduced. PMID- 8450752 TI - Real-time position monitoring of invasive devices using magnetic resonance. AB - Techniques which can be used to follow the position of invasive devices in real time using magnetic resonance (MR) are described. Tracking of an invasive device is made possible by incorporating one or more small RF coils into the device. These coils detect MR signals from only those spins near the coil. Pulse sequences which employ nonselective RF pulses to excite all nuclear spins within the field-of-view are used. Readout magnetic field gradient pulses, typically applied along one of the primary axes of the imaging system, are then used to frequency encode the position of the receive coil(s). Data are Fourier transformed and one or more peaks located to determine the position of each receiver coil in the direction of the applied field gradient. Subsequent data collected on orthogonal axes permits the localization of the receiver coil in three dimensions. The process can be repeated rapidly and the position of each coil can be displayed in real-time. PMID- 8450753 TI - Evolution of the alpha-crystallin/small heat-shock protein family. AB - The common characteristic of the alpha-crystallin/small heat-shock protein family is the presence of a conserved homologous sequence of 90-100 residues. Apart from the vertebrate lens proteins--alpha A- and alpha B-crystallin--and the ubiquitous group of 15-30-kDa heat-shock proteins, this family also includes two mycobacterial surface antigens and a major egg antigen of Schistosoma mansoni. Multiple small heat-shock proteins are especially present in higher plants, where they can be distinguished in at least two classes of cytoplasmic proteins and a chloroplast-located class. The alpha-crystallins have recently been found in many tissues outside the lens, and alpha B-crystallin, in particular, behaves in many respects like a small heat-shock protein. The homologous sequences constitute the C-terminal halves of the proteins and probably represent a structural domain with a more variable C-terminal extension. These domains must be responsible for the common structural and functional properties of this protein family. Analysis of the phylogenetic tree and comparison of the biological properties of the various proteins in this family suggest the following scenario for its evolution: The primordial role of the small heat-shock protein family must have been to cope with the destabilizing effects of stressful conditions on cellular integrity. The alpha-crystallin-like domain appears to be very stable, which makes it suitable both as a surface antigen in parasitic organisms and as a long-living lens protein in vertebrates. It has recently been demonstrated that, like the other heat-shock proteins, the alpha-crystallins and small heat-shock proteins function as molecular chaperones, preventing undesired protein-protein interactions and assisting in refolding of denatured proteins. Many of the small heat-shock proteins are differentially expressed during normal development, and there is good evidence that they are involved in cytomorphological reorganizations and in degenerative diseases. In conjunction with the stabilizing, thermoprotective role of alpha-crystallins and small heat-shock proteins, they may also be involved in signal transduction. The reversible phosphorylation of these proteins appears to be important in this respect. PMID- 8450754 TI - Molecular evolution of a repetitive region within the per gene of Drosophila. AB - The clock gene period (per) controls a number of biological rhythms in Drosophila. In D. melanogaster, per has a repetitive region that encodes a number of alternating threonine-glycine residues. We sequenced and compared this region from several different Drosophila species belonging to various groups within the Drosophila and Sophophora subgenera. This part of per shows a great variability in both DNA sequence and length. Furthermore, analysis of the data suggests that changes in the length of this variable region might be associated with amino acid replacements in the more conserved flanking sequences. PMID- 8450755 TI - The vertebrate genome: isochores and evolution. AB - Vertebrate genomes are mosaics of isochores--namely, of long (> 300 kb), compositionally homogeneous DNA segments that can be subdivided into a small number of families characterized by different GC levels. In the human genome (which is representative of a number of mammalian genomes, and, more broadly, of the genomes of warm-blooded vertebrates), the compositional range of isochores is 30%-60% GC, and five families of isochores have been identified: two GC-poor families, L1 and L2, together representing 62% of the genome, and three GC-rich families, H1, H2, and H3, representing 22%, 9%, and 3%, respectively (the remaining 4% of the genome is formed by satellite and ribosomal DNA). Gene concentration is strikingly nonuniform, being highest in the H3 isochore family, lowest in the L1 + L2 families, and intermediate in the H1 + H2 families. The H3 family corresponds to T(elomeric) bands of metaphase chromosomes, and the L1 + L2 families correspond to G(iemsa) bands, whereas R(everse) bands comprise both GC poor and GC-rich isochores. The compositional distributions of large genome fragments, of exons (and their codon positions), and of introns are correlated with each other. They represent compositional patterns and are very different between the genomes of cold- and warm-blooded vertebrates, mainly in that the former are much less heterogeneous in base composition and never reach the highest GC levels attained by the latter. Only relatively small compositional differences are found among the genomes of either cold- or warm-blooded vertebrates. Compositional patterns allow one to define two modes in genome evolution: a conservative mode, with no compositional change, and a transitional (or shifting) mode, with compositional changes. The conservative mode can be observed among either cold- or warm-blooded vertebrates. The transitional mode comprises both major and minor compositional changes. In vertebrate genomes, the major changes are associated with the appearance of GC-rich and very GC-rich isochores in mammalian and avian genomes. Mutational biases play a role in both modes of compositional evolution. According to one viewpoint, the fixation of compositionally biased mutations is responsible for the transitional mode of evolution of bacterial genomes; in the conservative mode of evolution of vertebrates, they accomplish their role in conjunction with differences either in chromatin structures that modulate replication errors or in chromatin transcriptional activities that may lead to various extents of repair-DNA synthesis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8450756 TI - Allelic genealogy and human evolution. AB - Genetic variation at most loci examined in human populations indicates that the (effective) population size has been approximately 10(4) for the past 1 Myr and that individuals have been genetically united rather tightly. Also suggested is that the population size has never dropped to a few individuals, even in a single generation. These impose important requirements for the hypotheses for the origin of modern humans: a relatively large population size and frequent migration if populations were geographically subdivided. Any hypothesis that assumes a small number of founding individuals throughout the late Pleistocene can be rejected. Extraordinary polymorphism at some loci of the major histocompatibility complex (Mhc) rules out the past action of severe bottlenecks, or the so-called founder principle, which invokes only a small number of founding individuals when a new species emerges. This conclusion may be extended to the 35-Myr-old history of the human lineage, because some polymorphism at Mhc loci seems to have lasted that long. Furthermore, although the population structure prior to the late Pleistocene is less clear, owing to the insensitivity of Mhc alleles, even to low levels of migration, the nature of Mhc polymorphism suggests that the effective size of populations leading to humans was as large as 10(5). Hence, the effective population size of humans might have become somewhat smaller in most of the late Pleistocene. The reduction could be due either to the then adverse environment in the Old World and/or to the increased migration rate. It is also argued that population explosion fostered by the agriculture revolution has had significant effects on incorporating new alleles into human populations. PMID- 8450757 TI - Forbidden synonymous substitutions in coding regions. AB - In the evolution of highly conserved genes, a few "synonymous" substitutions at third bases that would not alter the protein sequence are forbidden or very rare, presumably as a result of functional requirements of the gene or the messenger RNA. Another 10% or 20% of codons are significantly less variable by synonymous substitution than are the majority of codons. The changes that occur at the majority of third bases are subject to codon usage restrictions. These usage restrictions control sequence similarities between very distant genes. For example, 70% of third bases are identical in calmodulin genes of man and trypanosome. Third-base similarities of distant genes for conserved proteins are mathematically predicted, on the basis of the G+C composition of third bases. These observations indicate the need for reexamination of methods used to calculate synonymous substitutions. PMID- 8450758 TI - Nonlinear relationships among evolutionary rates identify regions of functional divergence in heat-shock protein 70 genes. AB - The neutral theory predicts that, in comparisons among related genes, the number of amino acid replacements per site in a given gene region should be a linear function of that in another region of the same gene, unless the genes have diverged functionally in one region. Therefore, nonlinearity of this relationship can be used to identify regions of possible functional divergence among members of a multigene family. This method of analysis was applied to members of the heat shock protein 70 (HSP70) gene family, which encode highly conserved ATP-dependent chaperone proteins found in all organisms. A nonlinear relationship was found between the rate of amino acid replacement in the conserved IA domain of the ATPase portion of the molecule and that in other ATPase domains and the peptide binding domain. These results suggest that genes in the HSP70 subfamily C (dnaK of bacteria and SSC1 of yeast) may have diverged functionally from other subfamilies in the ATPase domains, especially IIB, whereas SSB1 of yeast has diverged markedly in the peptide-binding domain. Functional divergence within these regions is consistent with what is known about functional differences between the HSP70 subfamilies in yeast. PMID- 8450759 TI - Ribosomal RNA secondary structure: compensatory mutations and implications for phylogenetic analysis. AB - Using sequence data from the 28S ribosomal RNA (rRNA) genes of selected vertebrates, we investigated the effects that constraints imposed by secondary structure have on the phylogenetic analysis of rRNA sequence data. Our analysis indicates that characters from both base-pairing regions (stems) and non-base pairing regions (loops) contain phylogenetic information, as judged by the level of support of the phylogenetic results compared with a well-established tree based on both morphological and molecular data. The best results (the greatest level of support of well-accepted nodes) were obtained when the complete data set was used. However, some previously supported nodes were resolved using either the stem or loop bases alone. Stem bases sustain a greater number of compensatory mutations than would be expected at random, but the number is < 40% of that expected under a hypothesis of perfect compensation to maintain secondary structure. Therefore, we suggest that in phylogenetic analyses, the weighting of stem characters be reduced by no more than 20%, relative to that of loop characters. In contrast to previous suggestions, we do not recommend weighting of stem positions by one-half, compared with that of loop positions, because this overcompensates for the constraints that selection imposes on the secondary structure of rRNA. PMID- 8450760 TI - Different modes of Mhc evolution in primates. AB - The human major histocompatibility complex (Mhc) is a chromosomal segment approximately 4 million bp long that contains > or = 84 genes. Some of these genes code for the class I and class II molecules, while the remaining genes code for complement components, cytochrome P450, tumor necrosis factor, and many other, unrelated proteins. We demonstrate on three examples (DP, C4-CYP21, and DRB) that different regions of the Mhc have different evolutionary histories. The organization of the DP region, which in humans contains four genes, was established in the ancestral Anthropoidea or earlier and has not changed since. The duplication that generated the two C4-CYP21 modules occurred in the ancestral Catarrhini or earlier, but the region has been undergoing periodic homogenizations via unequal crossing-over, which make paralogous genes in the same species more similar to each other than to orthologous genes of different species. The eight or nine genes of the DRB region were also generated in the ancestral Catarrhini, but the region has since been subject to frequent rearrangements, which generated various DRB haplotypes. Not only the alleles but, in part, also the haplotype polymorphism is evolving transspecifically. The DRB region of the Platyrrhini has an origin different from that of the Catarrhini. The picture emerging from these studies is that of both stability in some regions of the Mhc and tremendous evolutionary instability in other regions. PMID- 8450761 TI - Phylogenetic diversification of immunoglobulin genes and the antibody repertoire. AB - Immunoglobulins are encoded by a large multigene system that undergoes somatic rearrangement and additional genetic change during the development of immunoglobulin-producing cells. Inducible antibody and antibody-like responses are found in all vertebrates. However, immunoglobulin possessing disulfide-bonded heavy and light chains and domain-type organization has been described only in representatives of the jawed vertebrates. High degrees of nucleotide and predicted amino acid sequence identity are evident when the segmental elements that constitute the immunoglobulin gene loci in phylogenetically divergent vertebrates are compared. However, the organization of gene loci and the manner in which the independent elements recombine (and diversify) vary markedly among different taxa. One striking pattern of gene organization is the "cluster type" that appears to be restricted to the chondrichthyes (cartilaginous fishes) and limits segmental rearrangement to closely linked elements. This type of gene organization is associated with both heavy- and light-chain gene loci. In some cases, the clusters are "joined" or "partially joined" in the germ line, in effect predetermining or partially predetermining, respectively, the encoded specificities (the assumption being that these are expressed) of the individual loci. By relating the sequences of transcribed gene products to their respective germ-line genes, it is evident that, in some cases, joined-type genes are expressed. This raises a question about the existence and/or nature of allelic exclusion in these species. The extensive variation in gene organization found throughout the vertebrate species may relate directly to the role of intersegmental (V<==>D<==>J) distances in the commitment of the individual antibody-producing cell to a particular genetic specificity. Thus, the evolution of this locus, perhaps more so than that of others, may reflect the interrelationships between genetic organization and function. PMID- 8450762 TI - Mutagenicity of aristolochic acids (I, II) and aristolic acid I in new YG strains in Salmonella typhimurium highly sensitive to certain mutagenic nitroarenes. AB - Aristolochic acid I and II, two naturally occurring nitroaromatics, were studied for their mutagenicity in Salmonella typhimurium tester strains YG1020, 1021, 1024, 1025, 1026 and 1029 without exogenous metabolic activation. These strains contain multicopy plasmids which carry the genes for the classical bacterial nitroreductase or O-acetyltransferase. The strains TA98, TA100 and TA1537 were included in the study for comparison. Aristolic acid I, the analogue lacking the nitro group, and its sodium salt were also tested. Both aristolochic acids revealed mutagenicity in the respective YG strains derived from TA100, but the effect was no stronger than with the parent strain. Only weak activity was observed in TA98 and some YG strains derived from it. Aristolochic acid II was generally the more active compound. Aristolic acid I and its sodium salt did not exhibit any mutagenicity in any tester strain. From the results the following conclusions were drawn. (i) Only the nitro group is important for the mutagenicity of the aristolochic acids in S. typhimurium. (ii) It is suggested that aristolochic acid II is so efficiently metabolized by the classical bacterial nitroreductase that the additional activity produced from the YG strains no longer affects the metabolic activation. (iii) The methoxy group is probably responsible for the lower activity of aristolochic acid I, producing steric hindrance for binding of the genetically active intermediate to DNA or for binding of the substrate to the active site of the enzyme(s). PMID- 8450763 TI - Acrylamide; induction of DNA damage, chromosomal aberrations and cell transformation without gene mutations. AB - The genotoxic potential of acrylamide monomer (AA), a compound familiar as a raw material of polyacrylamide electrophoresis gel, was extensively investigated in vitro. The results were clear cut: AA did not induce any gene mutations in Salmonella/microsome test systems (TA98, TA100, TA1535, TA1537), Escherichia coli/microsome assay (WP2 uvrA-) up to a dose of 50 mg AA/plate, or in HPRT-locus in Chinese hamster V79H3 cells (AA, 1-7 mM, 24 h treatment). On the other hand, AA showed a strong positive response: (a) in a Bacillus subtilis spore-rec assay (DNA damage) at 10-50 mg/disc, (b) to a chromosomal structural change test (AA, 2 5 mM, 24 h treatment), (c) to a polyploidy test (AA, 1-5 mM, 24 h treatment) in Chinese hamster V79H3 cells, (d) to a cell transformation assay in mouse BALB/c3T3 cells (AA, 1-2 mM, 72 h treatment). Sister chromatid exchange was also weakly but significantly induced by AA (AA, 1-2.5 mM, 24 h treatment) in Chinese hamster V79H3 cells. Carcinogenic potential of AA was reported in mice and rats several years ago. AA thus seems to be a typical clastogenic rodent carcinogen without any gene mutation potential. Furthermore, this experiment showed for the first time positive response of AA to a microbial test system (B. subtilis spore rec assay). PMID- 8450764 TI - Is there evidence for directed mutation in bacteria? PMID- 8450765 TI - Incidence of micronuclei in oral mucosa of users of tobacco products singly or in various combinations. AB - Frequencies of micronucleated cells (MNCs) were analyzed in the exfoliated buccal mucosa of normal healthy individuals from different parts of India who were regularly using either areca nut alone, mava, tamol, tobacco with lime, dry snuff or masheri. The analyses were also carried out among oral submucous fibrosis patients who had the habit of chewing either mava or areca nut. Compared with 'no habit' healthy individuals, all the groups, irrespective of their type of habit, had significantly higher frequencies of MNCs. PMID- 8450766 TI - Analysis of micronuclei induced by 2-chlorobenzylidene malonitrile (CS) using fluorescence in situ hybridization with telomeric and centromeric DNA probes, and flow cytometry. AB - Micronuclei (MN) induced in NIH 3T3 cells by the tear gas 2-chlorobenzylidene malonitrile (CS) were studied in detail using fluorescence in situ hybridization (FISH). The chromosomal composition of CS-induced MN was analysed by simultaneous use of DNA probes for the telomeric hexamer repeat (TTAGGG) and for mouse major satellite DNA. The majority of CS-induced MN, 63-73% of all CS-induced MN at doses from 10 to 30 microM CS, revealed centromeric signals and several telomeric signals suggesting their origin from whole chromosomes. Almost 50% of all CS induced MN showed one centromeric signal and were assumed to contain one single chromosome. Only 4.5% of all MN did not show any signal and 23-28% showed telomeric signals only, thus containing acentric fragments. Based on the experimental data from FISH the distribution of the DNA content of CS-induced MN was calculated assuming random breakage of chromosomes, and random combination of chromosomes and chromosome fragments. Good agreement between calculated MN distributions and distributions measured by flow cytometry was obtained. By sorting MN with distinct DNA content and hybridization of the sorted MN with the centromeric probe, regions in the MN distribution containing mainly MN with single whole chromosomes could be demonstrated. PMID- 8450767 TI - Molecular spectrum of background mutation at the hprt locus in human T lymphocytes. AB - The molecular basis of somatic mutation at the hypoxanthine-guanine phosphoribosyl-transferase (hprt) locus in human 6-thioguanine resistant T-cell clones from 17 individuals has been studied by Southern blot analysis, multiplex PCR (polymerase chain reaction) and direct sequencing of PCR amplified hprt cDNAs or genomic DNA. Twenty-three novel mutations were detected, which in addition to previously described mutations provide a background mutational spectrum based on a total of 45 hprt mutations in human T-cells. Twenty T-cell mutants had base substitutions in the coding region leading to 15 missense and five nonsense mutations. In addition to five frameshift mutations caused by four small deletions and one duplication, seven splice mutations, three of them with skipping of exon 8, were detected. Thirteen genomic structural alterations have also been identified; one of these had a genomic exon 1 deletion with a GGCCGG hexamer in both breakpoints. PMID- 8450768 TI - Quercetin and the mutagenicity of wines. AB - Various studies have shown the mutagenicity of red wine. The major mutagens identified in red wine have been flavonoids, i.e. rutin and its aglycone quercetin. Besides flavonoids, however, it has recently been reported that H2O2 may account for the mutagenicity of red wine in the L-Arabinose resistance test. In the present study we report on the role of flavonoids in the mutagenicity of red wine in the Ames assay. Different wines from Portugal and Spain have been tested after concentration in XAD-2 columns in strains TA98 and TA104 of Salmonella typhimurium concurrently with the determination of the respective content of quercetin by HPLC. A similar approach was used for pilot scale productions of red wines. In all cases quercetin could be demonstrated as the major mutagen in red wines. The levels of quercetin in finished wines and during the wine-making process showed a good fit with the levels of mutagenicity detected. Catalase had no effect whatsoever on the mutagenicity of wines in both TA98 and TA104. These results do not rule out a role for H2O2 in the mutagenicity of wines, detected in other genetic end-points, because H2O2 can be formed from the auto-oxidation of quercetin. PMID- 8450770 TI - Detection of chemical mutagens using Muta Mouse: a transgenic mouse model. AB - A transgenic mouse strain with a high copy number of rescuable lacZ sequences was evaluated for its effectiveness in detecting lacZ- mutations in selected tissues. Procarbazine, cyclophosphamide, ethylnitrosourea, 7,12-dimethylbenz[a]anthracene (DMBA), acrylamide and chlorambucil were tested following either single or repeated dosing regimens. Bone marrow, liver, skin and testis tissues were selected to assess as target sites for mutation. Bone marrow, liver and testis tissues were examined for mutation following exposures to ethylnitrosourea and chlorambucil. Increased mutant frequencies were found for both chemicals in all three tissues. Bone marrow tissue was examined for mutation following procarbazine, cyclophosphamide and acrylamide exposures, and skin was examined for mutation following dermal application of DMBA. Mutation induction was observed in all cases. The results obtained from this investigation demonstrate the applicability of this transgenic mouse as an effective model to detect and analyze gene mutation in selected organs including germinal tissues. Studies of organotrophic chemical mutagens and carcinogens are possible with this model as are studies of the susceptibility of germinal tissues to mutagen exposures. PMID- 8450769 TI - Performance of 181 chemicals in a Drosophila assay predominantly monitoring interchromosomal mitotic recombination. AB - An evaluation is presented of the effects of 181 chemicals in the (white/white+) (w/w+) eye mosaic assay, an in vivo short-term test measuring genetic damage in somatic cells of Drosophila after treatment of larvae. The genetic principle of this system is loss of heterozygosity for the wild-type reporter gene w+, an event predominantly resulting from homologous interchromosomal mitotic recombination between the two X chromosomes of female genotypes. The w/w+ eye mosaic test detects a broad spectrum of DNA modifications, since all distinct classes of genotoxins are monitored. Non-DNA-reactive chemicals are in principle not detected by this system. Occasional positive responses obtained for chemicals such as amitrole, ethionine and hexachloeroethane are probably not related to the mechanism responsible for their tumorigenicity. The principle outcome of this analysis is the necessity for classification of responses into three categories. (i) Positive, '++'. The 92 chemicals (Tables II and III) falling into this category were clearly recombinagenic in the assay, meaning that dose-response relations were obtained (or could have been established as was evident from the strong responses obtained at one or two exposure doses). Among the 92 chemicals were 49 promutagens including volatile chemicals such as vinyl bromide and vinyl chloride. (ii) Marginally positive, '+w'. The definition of a weakly positive response is the absence of a dose-response relationship due to the fact that a weak but reproducible effect, in most cases no more than a doubling of the spontaneous clone frequency, is inherently related to toxicity. The 40 chemicals (Tables IV and V) belonging to this category mainly represented four distinct types. (a) Procarcinogens, such as 2-acetylaminofluorene, dibenz[a,h]anthracene, p-dimethylaminoazobenzene, 2-naphthylamine and safrole, for which metabolic conversion was the apparent problem in the assay. (b) Electrophilic chemicals of high nucleophilic selectivity: acrolein, acrylamide, acrylonitrile, epichlorohydrin, chloroethylisocyanate, 1,2-epoxybutane, N-methyl-n vinylacetamide, methyl vinylketone, 2-methyl-2-vinyloxirane and methyl vinylsulfone. These chemicals have a relatively low DNA reactivity. Chloroethylisocyanate was active only in the absence of excision repair, suggesting that efficient DNA repair is the cause for the weak genotoxic effectiveness of these genotoxins. (c) Spindle poisons (Table V) were active at rather low but toxic exposure levels. Irregularities in the structure of ommatidia were seen at dose levels producing no more than 2- to 3-fold increases in clone frequencies. (d) The fourth group consisted of chemicals generally regarded as non-genotoxic carcinogens: amitrole, ethionine, ethylurea, tetrachloroethylene and thiourea. Their weak responses were always accompanied by signs of toxicity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8450771 TI - Inducible protective processes in animal systems: IV. Adaptation of mouse bone marrow cells to a low dose of ethyl methanesulfonate. AB - Ethyl methanesulfonate (EMS), a monofunctional alkylating agent, was used in the present investigations to investigate the induction of adaptive response (inducible protective processes) in mitotic cells of Swiss albino mouse. When a low (conditioning) dose of 80 mg/kg body wt was challenged with a subsequent high (challenging) dose of 240 mg/kg body wt, after different time lags, the yield of chromosomal aberrations in bone marrow cells was found to be significantly reduced compared with that of the challenge dose. It appears, therefore, that a low dose of EMS offered resistance to the mitotic cells against further clastogenic effect of any challenge dose of EMS employed. It is clear from the results that the phenomenon of adaptive response can also be encountered in mammalian in vivo systems. PMID- 8450772 TI - Induction of micronuclei in cultured human lymphocytes exposed to quartz halogen lamps and its prevention by glass covers. AB - The light emitted by an uncovered tungsten halogen lamp (12 V, 50 W), equipped with a dichroic mirror, induced time-related and distance-related increases in the frequency of micronucleated lymphocytes following in vitro exposure. Peripheral blood lymphocytes from three healthy donors showed the same degree of sensitivity. This clastogenic effect could be ascribed to the emission of far-UV wavelengths (UVB and UVC) and was prevented by interposing a common glass cover. These results support the findings of our genotoxicity studies in repair deficient bacteria and carcinogenicity studies in hairless mice, thereby suggesting possible health hazards associated with illumination with halogen quartz bulbs, to which an enormous number of individuals are nowadays exposed. These hazards can be simply avoided by using glass covers. PMID- 8450773 TI - Report of a meeting of the Industrial Genotoxicology Group on modifications to in vitro genotoxicology assays required for testing difficult materials. PMID- 8450774 TI - The impact of molecular genetics on clinical medicine. PMID- 8450775 TI - Diabetes ambulatory care: a strategy for the future. PMID- 8450776 TI - Slow-release overdose. PMID- 8450777 TI - Trends in neural tube defects 1980-1989. AB - OBJECTIVES: To determine trends in prevalence of neural tube defects in Australia over the past decade; to investigate the impact of terminations of pregnancy on the birth prevalence of neural tube defects; and to provide a baseline against which to evaluate the potential effects of preventive public health measures. DATA SOURCES: Two population-based registries in Victoria and Western Australia and a statewide survey from Tasmania. DESIGN AND METHOD: A cohort study. Data on the numbers and the prevalence proportions of neural tube defects from three States--Western Australia, Victoria and Tasmania--were compared by Poisson regression. RESULTS: The prevalence proportions for all neural tube defects for all three States remained level over the study period 1980-1989. Terminations of pregnancy for all neural tube defects increased significantly over the decade in all three States. By 1989, 39.9% of all neural tube defects were ascertained as terminations before 20 weeks' gestation, while 10 years previously only 2.9% were. The percentage of cases of anencephaly ascertained as terminations of pregnancy increased from 4.8% in 1980 to 58.6% in 1989. Corresponding figures for spina bifida were 1.4% (1980) and 26.9% (1989), and for encephalocele 0% (1980) and 12.5% (1989). This increase in terminations was associated with a decrease per year in the birth prevalence proportion for anencephaly of 7.0%, for spina bifida of 4%, and for encephalocele of 11.0%, and a reduction in the risk of a birth with a neural tube defect in 1989 of 47% compared with the risk in 1980. CONCLUSION: Complete ascertainment of all terminations for neural tube defects as well as births with neural tube defects is necessary to provide reliable baseline data on the prevalence of neural tube defects. Such data are essential in evaluating primary preventive measures such as the effect of an increase in folic acid intake by women of child-bearing age. PMID- 8450778 TI - Human immunodeficiency virus notifications for aborigines and Torres Strait Islanders in Queensland. AB - OBJECTIVE: To describe the epidemiology of HIV infection based on notifications of HIV infection in Aboriginal and Torres Strait Islander people in Queensland and to review their implications for Aboriginal and Torres Strait Islander communities. DESIGN: Descriptive study of data obtained through HIV notifications to the AIDS Medical Unit, Specialised Health Services, Queensland Health from 1 July 1985 to 31 August 1991. SUBJECTS: Aboriginal and Torres Strait Islander people of Queensland. MAIN OUTCOME MEASURES: Centers for Disease Control (CDC) classification of HIV infection, as at 31 August 1991. RESULTS: Twenty-nine individuals identified as Aboriginal or Torres Strait Islander were notified as positive for HIV antibodies in the period 1 July 1985 to 31 August 1991. Of those diagnosed, three were female and 26 male. At 31 August 1991, only 10 were asymptomatic (CDC Group II, III), eight were symptomatic (AIDS-related complex) and 11 were diagnosed as having AIDS. Seven of those with a diagnosis of AIDS had died by the end of the study period. By comparison, 1158 non-Aboriginal or Torres Strait Islander people were notified for the same time period. Of these, 48 were female, 1105 were male and five were transsexual. In the non-Aboriginal and Torres Strait Islander group, 633 were asymptomatic and 297 were diagnosed with AIDS. By the end of the study period, 228 had died. CONCLUSIONS: The data show an estimated prevalence of diagnosed HIV infection in Aboriginal and Torres Strait Islander people in Queensland comparable with the rest of the population. Cases are distributed throughout the State, though some clustering is evident. There has been a stable pattern of notifications over the past five years. The proportion of asymptomatic (CDC groups II, III) HIV-positive Aboriginal and Torres Strait Islander clients was significantly lower than for the non Aboriginal and Torres Strait Islander group. These data have implications in terms of projections of total cases, diagnosed and undiagnosed, and relative access to the advantages attending early diagnosis. PMID- 8450779 TI - The prevalence of Giardia and other intestinal parasites in children, dogs and cats from aboriginal communities in the Kimberley. AB - OBJECTIVE: To determine the prevalence of Giardia duodenalis and other intestinal parasites in children, dogs and cats from Aboriginal communities in the west Kimberley region of Western Australia. DESIGN: A four-year parasitological survey of faecal specimens from humans and faecal and intestinal specimens from dogs and cats. SETTING: Local hospital servicing Aboriginal communities surveyed in this study and the Veterinary School, Murdoch University. POPULATION: Children (under 14 years) and adults, as well as dogs and cats, from five Aboriginal communities. RESULTS: G. duodenalis was the most prevalent parasite in children and adults (32.1% in children, n = 361; 12.5% in adults, n = 24). Human infections with Hymenolepis nana (20.5%) and Entamoeba coli (13.0%) were also common. Ancylostoma duodenale (1.3%), Pentatrichomonas hominis (1.0%), Chilomastix mesnili (0.52%), Entamoeba hartmanni (0.52%), Sarcocystis sp. (0.52%), Trichuris trichiura (0.26%), Enterobius vermicularis (0.26%), Strongyloides stercoralis (0.26%) and Isospora belli (0.26%) were present at low rates. Dogs were most commonly infected with Ancylostoma caninum (51.1%) and G. duodenalis (17.0%). Cats were found to have a high prevalence of Ancylostoma tubaeforme (18.2%), Toxoplasma gondii (18.2%), Isospora felis (15.1%) and Spirometra erinacei (15.1%). CONCLUSIONS: This study has shown that children from Aboriginal communities in the west Kimberley region of Western Australia, particularly in the age group one to five years, are commonly infected with intestinal parasites. The dogs and cats in these communities are also infected. The high prevalence rates of Giardia and other enteric parasites in this survey are indicative of poor living conditions and low levels of hygiene. In addition, the high prevalence of hookworm and Giardia infection in dogs and hookworm and Toxoplasma infection in cats is of potential zoonotic significance for humans in these communities. PMID- 8450780 TI - Observations on strongyloidiasis in Queensland aboriginal communities. AB - OBJECTIVE: To report the prevalence and distribution of infections with the parasitic nematode Strongyloides stercoralis in the Aboriginal and Torres Strait Islander communities of Queensland. DESIGN: A 20-year retrospective survey of computerised data and selected files from the former Aboriginal Health Programme (AHP) of the State Health Department of Queensland, based on cases diagnosed by the microscopic examination of preserved faecal specimens. Findings were compared with figures published in annual reports. STUDY POPULATION: Children under 15 years of age from 122 Aboriginal and Torres Strait Islander communities. RESULTS: Numbers of specimens examined varied widely according to time and place, as did detected infection rates. In 32,145 faecal samples examined by AHP microscopists during 1972-1991 the overall infection prevalence was 1.97%. Strongyloides larvae were found in only 52 of 122 communities. The parasite was absent from many small, southern inland communities, and the prevalence of infection increased in northern regions with summer wet seasons. On average, it was highest in Doomadgee (12%), where a peak prevalence of 27.5% (92/334 children examined) was detected in a wet season survey. Some infections resolved spontaneously, while others persisted for more than four years. At Gununa (Mornington Island), the prevalence fell from 26.2% to below 7% after thiabendazole treatment of most infected children, and remained at this level for at least four years. Single stool examinations by experienced microscopists may have failed to diagnose at least 26% of infected cases. The records give no indication of the clinical impact of strongyloidiasis. CONCLUSIONS: Strongyloidiasis is well established in many Aboriginal communities of north-eastern Australia. Children appear to be the major reservoirs of infection; the prevalence in adults is probably much lower. Failing improvements in community sanitation and hygiene, it may be possible to reduce significantly, if not eradicate, the infection by selectively treating diagnosed children with thiabendazole. PMID- 8450781 TI - The Fitzroy Valley Pap Smear Register. Cervical screening in a population of Australian aboriginal women. AB - OBJECTIVE: To describe the operation of the Fitzroy Valley Pap Smear Register, a population-based call and recall system for cervical screening for Aboriginal women, and the prevalence of cervical abnormalities in the women screened. DESIGN: Descriptive study. SETTING: An Aboriginal community in the far north-west of Western Australia. PARTICIPANTS: Aboriginal women aged 15 to 69 years, living in the Fitzroy Valley, Kimberley region. MAIN OUTCOME MEASURES: Proportion of eligible women on the Register; age distribution of women screened; prevalence of squamous cell abnormalities. RESULTS: In December 1990, there were 507 Aboriginal women on the Register, being 86.9% of the Aboriginal women in the Fitzroy Valley aged 15-69 years. During 1990, 53.6% of the target population were screened; 369 Pap smears were taken from 312 Aboriginal women. Seventy-six (24.3%) had never previously been screened. Considering only the first smear for each woman in the study period, 10.6% showed minor abnormalities, and 1.6% (95% confidence interval [CI], 0.2%-3.0%) had cervical intraepithelial neoplasia (CIN I, II or III); 2.6% has smears showing definite evidence of human papillomavirus (HPV) infection. For 15-19 year olds the prevalence of CIN was 4.7% (95% CI, 1.0%-13.3%). CONCLUSIONS: The study shows how an inexpensive call and recall system can ensure good coverage of cervical screening in a group of women who would otherwise be under screened. The overall prevalence of CIN in Aboriginal women in the Fitzroy Valley was lower than the figure for all Victorian women (3.6%--data from the Victorian Cytology Service). Although the numbers are small, the relatively high prevalence of CIN in young women is of some concern, and emphasises the importance of regular screening in this group. PMID- 8450782 TI - Dexfenfluramine in type II diabetes: effect on weight and diabetes control. AB - OBJECTIVE: To assess the effect of dexfenfluramine on weight loss, diabetic control and blood lipids in type II diabetics over a three-month period. DESIGN, SETTING AND PATIENTS: Forty overweight patients in the Diabetic Clinic, Fremantle Hospital, were studied in a double-blind, placebo-controlled trial with a run-in period of one month followed by three months on either dexfenfluramine or placebo. MAIN OUTCOME MEASURES: Changes in body weight, and fasting plasma glucose, glycosylated haemoglobin, plasma cholesterol and triglyceride levels. MAIN RESULTS: The median change in weight was -3.8 kg in the treatment group (Df) and +0.3 kg in the placebo group (PI) (P = 0.006). The median changes in fasting plasma glucose levels were -1.0 mmol/L (Df) and +0.6 mmol/L (PI) P = 0.010). The median changes in glycosylated haemoglobin levels were -1.4% (Df) and +0.2% (PI) (P = 0.002). The median changes in triglyceride levels were -0.3 mmol/L (Df) and +0.2 mmol/L (PI) (P = 0.017). Cholesterol level did not change significantly. CONCLUSION: Dexfenfluramine is effective in achieving weight loss and also improved diabetic control in obese type II diabetics over a three-month period. PMID- 8450783 TI - Diabetes in the workplace. Employment experiences of young people with diabetes mellitus. AB - OBJECTIVE: To assess some of the employment experiences of people with diabetes mellitus and to compare their experiences with those of a non-diabetic sibling control group. DESIGN: A questionnaire about employment experiences was administered to diabetic subjects aged 16-39 years, and an abbreviated questionnaire was administered to their eligible siblings. SETTING: The Illawarra area of New South Wales. PARTICIPANTS: The names of diabetic subjects were obtained from the Illawarra diabetes register. RESULTS: Interviews were conducted with 184 of 226 (81.4%) eligible diabetic subjects and with 70 eligible siblings. There were no significant differences between the diabetic subjects and their siblings with respect to educational achievements and rates of employment. Siblings reported a mean of 2.6 days sickness absenteeism in the year prior to the survey. Diabetics were absent from work for a mean of 4.5 days for reasons not related to their diabetes and for a mean of 2.6 days for diabetic causes. Within the diabetic group, 50% felt that having diabetes would make it more difficult to find another job, 33.7% felt that diabetes would influence their search for alternative employment and 19.6% felt that at some stage they had been refused employment because of their diabetes. Fifteen per cent of diabetics were aware of an example of discrimination and 24.2% of diabetics in employment had at some stage tried to hide their diagnosis from their employer. CONCLUSIONS: Diabetics do not appear disadvantaged compared with their siblings with respect to employment participation but are more likely to be absent from work due to sickness. However, many diabetic subjects had experienced a job refusal, had tried to hide their diagnosis from employers, were aware of examples of discrimination and were very negative about future employment prospects. PMID- 8450784 TI - HIV-related haematological disease. AB - Patients may be referred to a haematologist for clinical and laboratory evaluation of anaemia, neutropenia, thrombocytopenia or lymphoid disorders. Any of these may present the first opportunity to diagnose HIV infection. PMID- 8450785 TI - HIV-related gastrointestinal disease. AB - Gastrointestinal disease is common in patients infected with HIV and can represent the first significant clinical illness. Diarrhoea, dysphagia, abdominal pain, jaundice or gastrointestinal bleeding may be the result of opportunistic infection, AIDS-related neoplasia, or infection with HIV alone. The spectrum of gastrointestinal tract and liver involvement in HIV infection is broad and has been well reviewed recently. This article is selective in that the main emphasis is placed on the variety of ways that HIV may first declare itself with symptoms in the gastrointestinal tract. PMID- 8450786 TI - HIV-related skin disease. AB - Most patients with HIV infection will develop an HIV-related lesion of the skin or mucous membranes before their progression to AIDS. As the skin is readily observed by patients and easily examined by doctors, skin disease presents a good opportunity for the early diagnosis of HIV infection. PMID- 8450787 TI - Unusual features of herpes simplex or zoster infection that suggest HIV infection. AB - Patients with herpes simplex or zoster infections are common in most medical practices. These infections are also very important in HIV medicine, often presenting in an otherwise well person. Knowledge of the effects of immune deficiency on herpes simplex and zoster infection assists in determining when to consider HIV. PMID- 8450788 TI - Unexplained fever and drug reactions as clues to HIV infection. AB - Unexplained fever, usually self-limiting and often due to a viral infection, is commonly seen in many medical practices. When should a doctor consider HIV in relation to a patient's fever? PMID- 8450789 TI - Can we afford to transplant? PMID- 8450790 TI - Elements of molecular genetics. PMID- 8450791 TI - Slow-release verapamil poisoning. Use of polyethylene glycol whole-bowel lavage and high-dose calcium. AB - OBJECTIVE: To present three cases of slow-release verapamil poisoning that demonstrate the prolonged absorption of the drug and the role of polyethylene glycol and high-dose calcium in management. CLINICAL FEATURES: Three patients with slow-release verapamil poisoning are presented. An 18-year-old woman took 2.3 g and developed hypotension and bradyarrhythmias 18 hours after ingestion, despite gastric lavage and administration of charcoal at three hours. A 23-year old woman took 4.8 g and presented two hours later clinically unaffected. A 44 year-old woman presented 24 hours after taking 15-20 g. She had a systolic blood pressure of 50 mmHg, no measurable diastolic blood pressure and bradyarrhythmias. INTERVENTION AND OUTCOME: Case 1 responded to administration of 30 g of calcium and fluids intravenously. Case 2 was given polyethylene glycol on admission which resulted in passage of a tablet bezoar and no toxicity. Polyethylene glycol was ineffective in Case 3. She responded initially to high doses of calcium and other treatments, but subsequently died of hypotension and cardiac conduction block 39 hours after the overdose. CONCLUSION: The severity of poisoning with slow-release verapamil warrants aggressive pre-emptive treatment. Polyethylene glycol should be used routinely irrespective of the clinical state. High doses of calcium may be required to treat conduction block and hypotension. PMID- 8450792 TI - Decisions in clinical management. A case scenario. AB - A hypothetical case presentation is used to examine the process and repercussions of a complaint against the health system. Utility analysis and the "number needed to be treated" are seen as useful measures of the outcomes of actions taken in response to the complaint. The Theory of Continuous Improvement or Total Quality Management can be modified to allow constructive and profitable analysis of complaints to identify and correct faults in systems of medical and health care. A science of enantiology is proposed, which would develop these ideas, develop measures of benefit and study the changes that would follow a positive approach to the insights provided by complaints. PMID- 8450793 TI - Dilemmas in the management of the elderly diabetic. PMID- 8450794 TI - Cryptococcal meningitis in Papua New Guinea: ecology and the role of eucalypts. PMID- 8450795 TI - Gastrointestinal endoscopy. PMID- 8450796 TI - Pulmonary angiography in a non-teaching hospital over a 12-year period. PMID- 8450797 TI - An aid to laparoscopic hernioplasty--balloon dissection. PMID- 8450798 TI - Pseudomonas aeruginosa. PMID- 8450799 TI - Guide to the percentage "impairment" of the back, neck and pelvis. PMID- 8450800 TI - Guide to the percentage "impairment" of the back, neck and pelvis. PMID- 8450801 TI - Protocols for vegetative patients. PMID- 8450802 TI - Morbidity and treatment in general practice in Australia 1990-1991. PMID- 8450803 TI - Ethics committees: is the tail wagging the dog? PMID- 8450804 TI - Sudden death while lawnmowing. PMID- 8450805 TI - Sudden death while lawnmowing. PMID- 8450806 TI - Sotalol for cardiac arrhythmias. PMID- 8450807 TI - Atovaquone for Pneumocystis carinii pneumonia. PMID- 8450808 TI - [Vascular leiomyoma (angiomyoma) of the retroperitoneum. Clinical presentation as a cystic upper abdominal tumor]. PMID- 8450809 TI - [Paroxysmal hypokalemic paralysis--diagnosis and therapy]. PMID- 8450810 TI - [Heyde syndrome--association between calcifying aortic valve stenosis and gastrointestinal hemorrhage of uncertain origin]. PMID- 8450811 TI - [Central pontine myelinolysis in two patients after therapy for severe hyponatremia]. PMID- 8450812 TI - [Laurence-Moon-Bardet-Biedl syndrome]. PMID- 8450813 TI - [Aneurysm of the splenic artery--a rare differential diagnosis of a submucous stomach tumor]. PMID- 8450814 TI - [Differential diagnosis of initial manifestations of systemic lupus erythematosus]. PMID- 8450815 TI - [Focal meningoencephalitis as initial manifestation of Actinobacillus actinomycetem comitans endocarditis]. PMID- 8450816 TI - [Osteomalacia caused by vitamin D deficiency in a female Tamil immigrant]. PMID- 8450817 TI - [Deep venous thrombosis of the leg with severe lung embolism after varicella infection in an adult]. PMID- 8450818 TI - [26-year-old patient with recurrent semi-consciousness, tonic seizures and pathological EEG]. PMID- 8450819 TI - An historical perspective on home care policy. AB - Although home care has received increased policy attention in recent years, the health services literature does not offer a historical perspective. The way home care is viewed and the nature of its support have changed significantly, yet history also suggests continuity. The era of modern medicine has relegated the status of home care to that of a residual set of follow-up services and there has been a lack of consensus about the goals of home care. For about 75 years, the legitimacy of home care has depended upon claims that it would relieve utilization and costs of institutional care, which has served both to maintain its policy salience and to undermine its legitimacy. Profound demographic and fiscal changes have increased the demand for home care, especially among the chronically ill, but various issues remain unresolved. PMID- 8450820 TI - Life in the hospital: a review. AB - The ethnographic study of hospitalized patients' social worlds and individual experience, a once flourishing research tradition, has now largely vanished from the literature of social science. The disappearance of this tradition is accounted for by changes in the character of hospitals--decreasing lengths of stay, expansion of specialized units, and medicine's increased technical sophistication--that have weakened patients' social worlds and, perhaps, made patients' experience less consequential for health outcomes. If the ethnographic study of hospital patients is revitalized, it will take shape around a view of the patient as a newly empowered participant in decision-making processes. PMID- 8450821 TI - Round and round it goes: the epidemiology of childhood lead poisoning, 1950-1990. AB - In the 40 years from 1950 to 1990, lead epidemiology and public policy based on it made enormous strides. Exposure levels that caused concern in the medical and public health community fell from 80 to 10 micrograms/dL of blood. In the space of 20 years, beginning in 1970, first the surgeon general and then the CDC lowered the official "level of concern" from 50 or 60 to 10 micrograms/dL. The public health community has turned its attention from the prevention of poisoning that results in encephalopathy, mental retardation, and death to the reduction of exposure to avoid subtle neurobehavioral deficits that are detectable only in fairly large epidemiological studies. Numerous advances in technology and analysis have facilitated progress in lead epidemiology. In order to show that intellectual deficits were related to lead exposure rather than to such confounding variables as parental education, parental IQ, income, or parents' age at time of birth, researchers performed extensive regression analyses of fairly large sample populations, controlling for as many as 39 confounding variables. These analyses would have been virtually impossible but for the development of computer software programs that became available beginning in the late 1960s and early 1970s. Handling of large data bases, such as NHANES II, also required access to computer hardware and software not generally available earlier. The existence of the data depended on other technological innovations that made screening of large populations inexpensive and relatively simple. In 1973, erythrocyte protoporphyrin screening transformed testing for lead poisoning. With the advent of atomic absorption spectroscopy and rapid improvement in equipment for blood lead analysis, obtaining blood lead levels became less expensive and easier and produced more accurate results. Increasing attention both to preventing environmental contamination of samples and to controlling laboratory quality also improved the accuracy of data collected. Advances in screening and analytical technology made the mass screening of the 1970s possible--both the programs coordinated by the CDC and NHANES II. NHANES II showed the extent of the problem of lead exposure to be even greater than previously thought. It was estimated that in 1980 almost 2 percent of all children aged six months to five years had blood lead levels over the CDC level of concern of 30 micrograms/dL. More than 13 percent of black children had levels above 30 micrograms/dL. Lead was certainly the most widespread threat to child health in America. In 1985, when the CDC lowered the level of concern to 25 micrograms/dL, the population defined to be at risk tripled.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8450822 TI - Segregation, poverty, and empowerment: health consequences for African Americans. AB - Cities in the United States have undergone major social transitions during the past two decades. Three notable factors in these shifts have been the development of a black political elite sustained rates of black poverty, and intensified racial segregation. Indications of the effect of these social forces on black white differentials in health status have begun to surface in the research literature. This article reports analyses of data from all U.S. cities with a population of 50,000, at least 10 percent of which is black. These results indicate substantial geographic variation in black-white infant mortality rates. Racial residential segregation, black political empowerment, and black and white poverty are the characteristics that distinguish cities that have a high degree of disparity in black-white infant mortality from cities that do not. PMID- 8450823 TI - Childhood immunization programs: an analysis of policy issues. AB - Immunizations have been among the most successful of preventive interventions. However, concern exists in the United States that recent epidemics of vaccine preventable diseases and low rates of childhood immunizations may signal the existence of major underlying problems in immunization policy. Additionally, the effectiveness of national, state, and local public health programs in administering these and other preventive services to children has been called into question. This article examines the current state of childhood immunizations in this country and offers a broad range of suggestions for policy modification. PMID- 8450824 TI - How expenditure caps and expenditure targets really work. AB - Every organized payment system must contain its costs in order to keep within revenue without denying benefits. Fixed expenditure caps requiring the provider to operate within its annual financial grant can be imposed on organizations like hospitals, but are fiercely resisted by the medical profession. All financial arrangements with doctors are negotiated, including systems of fixed expenditure caps and more flexible expenditure targets. If the doctors accept the principle of caps and cooperate in achieving them, they do so only as part of a negotiated settlement to avoid a worse outcome. Government's power is minimized, even when government is the payer. Caps on the physicians' sector are unusual. Instead, we see the spread of flexible targeting systems, wherein cost overruns are compensated for by lower expenditure targets the following year. Medical associations in all countries resisted even these restraints for years, but eventually accepted them, provided that target setting, judgments of overruns, utilization control, and all other features are part of a joint negotiating system. Targeting systems are often complicated because they preserve the semiprivate character of statutory health insurance and they are the result of negotiated compromises. To succeed in controlling costs, they require the cooperation of the medical association and of the rank-and-file doctors--but they can succeed. The United States has enacted a small-scale targeting system for Medicare physician payments alone. It cannot become the method for universal health insurance, which must heed lessons from abroad. Only an all-payer system can cover an entire population and contain the costs of the system. A few government officials cannot dictate and implement expenditure goals, but a system of consultation is required for setting and carrying out targets. Impartial officials can regulate hospitals according to the guidelines produced by the consultations, but the record of the medical profession in the countries reviewed here is that they insist on negotiating the final rules and rates. Americans have become bewitched by the mirage of econometric formulas automatically governing a sector, but the real problem is to devise and operate a harmonious decision making system. PMID- 8450825 TI - Methemoglobinemia in an infant--Wisconsin, 1992. AB - Methemoglobinemia among infants is a rare and potentially fatal condition caused by genetic enzyme deficiencies, metabolic acidosis, and exposure to certain drugs and chemicals. The most widely recognized environmental cause of this problem is ingestion of nitrate-containing water. Ingestion of copper causes abdominal discomfort, nausea, diarrhea, and in cases of high-level exposure, vomiting. This report summarizes an investigation by the Division of Health, Wisconsin Department of Health and Social Services of methemoglobinemia associated with ingestion of nitrate- and copper-containing water in an infant during 1992. PMID- 8450826 TI - Classification of American Indian race on birth and infant death certificates- California and Montana. AB - The accuracy of infant mortality rates and other indices of the health of populations depends on the consistency of information collected from separate sources (e.g., birth and death certificates). Inconsistent recording of basic information such as race and ethnicity has resulted in underestimation of mortality among minority populations, particularly minority populations other than blacks. This report summarizes studies in California and Montana that describe and measure the magnitude of differences in the recording of race for American Indians/Alaskan Natives (AI/ANs) on birth and infant death certificates. PMID- 8450827 TI - Sliding-associated injuries in college and professional baseball--1990-1991. AB - Softball and baseball are among the most frequent causes of sports-related emergency department visits in the United States, accounting for an estimated 321,000 injuries in 1989. Approximately 71% of softball-related injuries are caused by sliding. The use of breakaway bases substantially decreases the risk for or occurrence of sliding-related injuries among recreational softball league players. This report summarizes the findings of a study on the impact of breakaway base use on sliding injuries among college and professional minor league baseball players. PMID- 8450828 TI - Cigarette smoking among adults--United States, 1991. AB - From 1965 through 1985, smoking prevalence in the United States declined at a rate of 0.5 percentage points per year, and from 1987 through 1990, the rate of decline accelerated to 1.1 percentage points per year. CDC monitors the use of tobacco in the United States to evaluate progress in reducing smoking prevalence. To determine the prevalence of smoking among U.S. adults during 1991, the National Health Interview Survey-Health Promotion and Disease Prevention (NHIS HPDP) supplement collected self-reported information on cigarette smoking from a representative sample of the U.S. civilian, noninstitutionalized population aged > or = 18 years. This report summarizes the results of this survey. PMID- 8450829 TI - Mouse 5-hydroxytryptamine5A and 5-hydroxytryptamine5B receptors define a new family of serotonin receptors: cloning, functional expression, and chromosomal localization. AB - Serotonin [5-hydroxytryptamine (5-HT)] is a neuromodulator that mediates a wide range of physiological functions by activating multiple receptors. Using a strategy based on amino acid sequence homology between 5-HT receptors that interact with guanine nucleotide-binding proteins, we have isolated from a mouse brain library a cDNA encoding a new serotonin receptor. Amino acid sequence comparisons revealed that this receptor was a close relative of the previously identified 5-HT5 receptor but was distant from all other 5-HT receptor subtypes; we therefore named it 5-HT5B. When expressed in COS-7 cells, the 5-HT5B receptor displayed a high affinity for the serotonergic radioligand 125I-lysergic acid diethylamide. Its pharmacological profile was distinct from that of all classic 5 HT receptor subtypes. However, the high affinity of the 5-HT5B receptor for 5 carboxamidotryptamine and its low affinity for sumatriptan indicated that it might correspond to recently described 5-HT1D-like binding sites that were labeled with [3H]5-carboxamidotryptamine and insensitive to sumatriptan. In situ hybridization experiments revealed that the 5-HT5B mRNA was expressed predominantly in the habenula and in the CA1 field of the hippocampus. We also determined the chromosomal localization of the 5-HT5A and 5-HT5B genes and of their human counterparts. The 5-HT5A gene colocalized with the mouse mutation reeler and the human mutation holoprosencephaly type 3, which both result in abnormal brain development, raising the possibility that the 5-HT5A receptor plays a role in brain development. PMID- 8450830 TI - Expression of multiple forms of cytochrome P450 mRNAs in primary cultures of rat hepatocytes maintained on matrigel. AB - Freshly isolated rat hepatocytes rapidly lose their cytochrome P450 (P450) proteins and mRNAs, with no evidence of subsequent restoration, after placement into traditional systems of primary culture on type I collagen. We examined the patterns of expression of 10 constitutively expressed P450 mRNAs in rat hepatocytes cultured for up to 5 days on a matrix of Matrigel, a reconstituted basement membrane that allows inducible expression of some P450s, and compared these patterns with those seen in hepatocytes cultured on type I collagen (Vitrogen). mRNA for each P450 was detected on Northern blots in samples prepared from freshly isolated male rat hepatocytes, and the amount of each mRNA decreased markedly during the first 2 days of culture in cells maintained on either matrix (decreases of 53-97% on Matrigel and 62 to > 99% on Vitrogen), in contrast to the level of NADPH-P450 oxidoreductase mRNA, which increased during this interval. On subsequent days, hepatocytes cultured on Matrigel expressed the individual P450 mRNAs in one of the following four patterns. 1) P450 1A2, 2A2, 2E1, and 3A1/2 mRNAs remained low throughout the 5-day culture period. 2) 2A1 mRNA increased between days 2 and 4 but then decreased on day 5. 3) 2B1/2, 2C6, 2C7, and 4A1 mRNAs increased continually between days 2 and 5, 4) The total mRNAs detected with a 2D probe remained at constant levels between culture days 2 and 5. Our results show that rat hepatocytes cultured on Matrigel in serum-free medium spontaneously reexpress the mRNAs for several constitutive P450s in form-specific patterns, and they suggest that the Matrigel culture system will be useful for identifying the underlying regulatory mechanisms. PMID- 8450831 TI - N-hydroxylation of benzamidine to benzamidoxime by a reconstituted cytochrome P 450 oxidase system from rabbit liver: involvement of cytochrome P-450 IIC3. AB - Previous investigations have provided evidence for the participation of the cytochrome P-450 (P-450) enzyme system in the established N-hydroxylation of benzamidine to benzamidoxime by microsomal fractions from rabbit liver homogenates. In the present investigation, a representative mixture of P-450 isoenzymes was first isolated from the livers of untreated rabbits and then, together with purified NADPH-P-450 reductase, successfully used in a reconstituted enzyme system for the N-hydroxylation of benzamidine. In order to identify the participating isoenzyme, the P-450 mixture was separated by preparative high performance liquid chromatography on an anion exchange column. A P-450 fraction was obtained that was able to transform benzamidine with a specific activity > 3-fold higher than that of the P-450 mixture. The electrophoretic and spectral properties, as well as the inhibition by monoclonal antibodies against P-450 IIC3, show that the isolated P-450 fraction must consist of one or more variants of the isoenzyme P-450 IIC3. By means of reconstitution experiments with highly purified variants of P-450 IIC3 from rabbit liver and with purified variants of P-450 IIC expressed by recombinant Escherichia coli, the participation of the two variants P-450 IIC3 (6 beta H) and P-450 IIC3 (6 beta L) in the N-hydroxylation of benzamidine was unequivocally confirmed. PMID- 8450832 TI - A first step in the development of gene therapy for colorectal carcinoma: cloning, sequencing, and expression of Escherichia coli cytosine deaminase. AB - We have developed a new approach involving gene therapy for the treatment of primary and metastatic tumors in the liver. As a first step toward the development of this gene therapy treatment for metastatic colorectal carcinoma, the Escherichia coli gene that encodes cytosine deaminase (CD) (EC 3.5.4.1) has been cloned. By using positive genetic selection, a plasmid carrying a 10.8 kilobase BamHI/EcoRI DNA insert was isolated that had CD enzymatic activity. Genetic screening, followed by enzymatic assays, identified a 3-kilobase DNA fragment that retained CD activity. Deamination of cytosine and 5-fluorocytosine (5-FC) by cloned CD was demonstrated. DNA and protein sequencing identified an open reading frame of 427 amino acids that encodes CD. To demonstrate that expression of CD in eukaryotic cells allows metabolism of the nontoxic prodrug 5 FC to the toxic metabolite 5-fluorouracil, CD was cloned into a eukaryotic expression vector and transfected into a human colorectal carcinoma cell line. Growth inhibition studies showed a shift in the IC50 for 5-FC from 17,000 microM in the parental cell line to 30 microM in cells expressing CD. PMID- 8450833 TI - Further characterization and purification of the flavin-dependent S-benzyl-L cysteine S-oxidase activities of rat liver and kidney microsomes. AB - Previously, we provided evidence that cysteine conjugate S-oxidase (S-oxidase) activities of rat liver and kidney microsomes may be associated with flavin containing monooxygenases (FMOs). In this study, the biochemical properties of these activities were further investigated. When NADPH was replaced by NADH, the S-oxidase activities were reduced significantly. Removal of the flavin moiety from microsomes significantly reduced the S-oxidase activities; however, addition of exogenous FAD or FMN restored the activities of the flavin-depleted microsomes. Solubilization of hepatic or renal microsomes with Emulgen 911, Nonidet P-40, Triton X-100, or 3-[(3-cholamidopropyl)dimethyl-ammonio]-1- propane sulfate or inclusion of the sulfhydryl-reactive agents Hg2+, N-ethylmaleimide, or iodoacetamide did not affect the S-oxidase activities, whereas solubilization of either hepatic or renal microsomes by cholate or heating of renal microsomes in the absence of NADPH significantly reduced the S-oxidase activities. In addition to male rat hepatic and renal microsomes, the S-oxidase activities were detected in lung microsomes of male rats and hepatic and renal microsomes of male mice and female rats and rabbits. The male rat kidney maintained the highest S-oxidase activity of all species and tissues examined. Whereas the aforementioned results provided further evidence for the S-oxidase activities being associated with FMOs, unambiguous evidence for this hypothesis was provided by the purification of the activities from rat liver (580-fold) and kidney (700-fold) microsomes and by the use of the isolated proteins in polyacrylamide gel electrophoresis, flavin content determinations, amino-terminal amino acid sequence analysis, amino acid composition analysis, and substrate kinetic studies. The findings that the S oxidases were immunoreactive with antibodies raised against the pig liver 1A1 isozyme but not with antibodies raised against the rabbit lung 1B1 isozyme and that the liver S-oxidase amino-terminal amino acid sequence was more comparable to the amino-terminal amino acid sequences of pig and rabbit liver 1A1 isozymes than to those of rabbit lung 1B1 and liver 1D1 isozymes provide evidence that the S-oxidases are related to the known FMO 1A1 isozymes. PMID- 8450834 TI - Human S31 serotonin receptor clone encodes a 5-hydroxytryptamine1E-like serotonin receptor. AB - We reported recently the molecular cloning of a genomic fragment, designated S31, that has an open reading frame of 1095 nucleotides, encoding a protein of 365 amino acids. Amino acid similarity analysis suggested that the S31 protein could be a guanine nucleotide-binding protein-coupled receptor pertaining to the serotonin receptor subfamily. Expression of the S31 open reading frame in murine L cells confirmed this, because it led to the appearance of serotonin-mediated inhibition of adenylyl cyclase activity, which was absent in the recipient L cells. We now report some aspects of the pharmacological profile of this receptor. We found that the relative potencies with which 5-hydroxytryptamine, 5 carboxamidotryptamine, methysergide, ergotamine, 8-hydroxydipropylaminotetralin, and trifluoromethylphenylpiperazine promote inhibition of adenylyl cyclase are as follows: 5-hydroxytryptamine >> methysergide >> ergotamine >> trifluoromethylphenylpiperazine > or = 8-hydroxydipropylaminotetralin > 5 carboxyamidotryptamine. This corresponds to the rank order of potencies assigned for these drugs for the 1E subtype of serotonin receptors discovered by Leonhardt and collaborators in human brain [J. Neurochem. 53:465-471 (1989)]. PMID- 8450835 TI - Pharmacological characteristics of the newly cloned rat 5-hydroxytryptamine2F receptor. AB - The rat 5-hydroxytryptamine (5-HT)2F (serotonin2F) receptor is a newly cloned member of the 5-HT2/1C receptor family. The pharmacology of the 5-HT2F receptor was explored using a variety of structurally different compounds in a radioligand binding assay. In addition, the 5-HT2F receptor was shown to stimulate production of inositol 1,4,5-trisphosphate in the transformed cells. Based on the affinities of the compounds tested, their known affinities for certain of the other 5-HT receptors, and the fact that activation of the cloned 5-HT2F receptor stimulates inositol 1,4,5-trisphosphate production, the 5-HT2F receptor was determined to be a novel receptor and a member of the 5-HT2/1C receptor family. In addition, several agonists and partial agonists were evaluated for contractile activity in the rat stomach fundus, and these activities were correlated with their binding affinities at the 5-HT2F receptor. A highly significant correlation was found, providing additional evidence that is consistent with the 5-HT2F receptor being the stomach fundal contractile receptor. [3H]5-HT had high affinity for this receptor both at 37 degrees and at 0 degree (Kd = 7.87 +/- 0.55 and 0.12 +/- 0.02 nM, respectively). The difference in affinity for [3H]5-HT at the two temperatures prompted an investigation of potential temperature-dependent differences in the binding affinities of agonists versus antagonists. Agonists such as 5-HT, 5-methoxytryptamine, etc., showed higher affinity for the 5-HT2F receptor at 0 degree than at 37 degrees, whereas antagonists such as methysergide, 1-naphthylpiperazine, etc., showed no difference in affinity for this receptor at the two different temperatures. Therefore, the affinity of a compound for the 5-HT2F receptor at 37 degrees versus 0 degree was shown to be useful for predicting agonist or antagonist activity. Additionally, information is provided about some of the structural requirements for the affinity of certain tryptamines at the 5-HT2F receptor. PMID- 8450836 TI - Binding of the K+ channel opener [3H]P1075 in rat isolated aorta: relationship to functional effects of openers and blockers. AB - P1075 [N-cyano-N'-(1,1-dimethylpropyl)-N"-3-pyridylguanidine], an analogue of the K+ channel opener pinacidil, was shown to be a K+ channel opener in rat aorta, based on (i) its ability to stimulate 86Rb+ efflux, (ii) its ability to relax contractions in response to noradrenaline under normal conditions (5 mM KCl) but not under depolarized conditions (55 mM KCl), and (iii) the sensitivity of these effects to inhibition by the sulfonylurea glibenclamide. In these assays, P1075 was approximately 20 times more potent than cromakalim. Using a tritiated derivative, [3H] P1075, specific binding could not be detected in microsomal preparations from various tissues. However, in rat aortic strips specific binding of [3H]P1075 has been observed and was reduced by lowering the temperature or by decreasing intracellular ATP levels via metabolic inhibition. Specific [3H]P1075 binding was influenced neither by depolarization (55 mM KCl) nor by lowering the pH from 7.4 to 6.0. Binding was inhibited by representatives from all major families of K+ channel openers, with potencies that correlated well with the potencies obtained in 86Rb+ efflux and relaxation studies. However, stimulation of 86Rb+ efflux occurred at 40 times higher concentrations than did binding (and vasorelaxation). Of the various inhibitors of the K+ channel openers tested, only the sulfonylureas inhibited [3H] P1075 binding with the same rank order of potencies as that required for inhibition of P1075-induced 86Rb+ efflux, although at higher concentrations. The results show that binding of [3H] P1075 is independent of membrane potential but decreases concomitantly with the intracellular ATP level. The excellent correlation between the potencies of the openers and sulfonylurea blockers in binding assays and functional studies suggests that the 'drug receptor' labeled by [3H]P1075 in rat isolated aorta is of functional relevance. However, the fact that binding of the openers occurred at concentrations considerably lower than those required for K+ channel opening and that binding of the sulfonylureas was only reflected at concentrations higher than those needed to block the channel requires complex models to link binding and effect, possibly involving two agonist binding sites coupled by negative cooperativity. PMID- 8450837 TI - Modulation of gating of cloned rat and human K+ channels by micromolar Zn2+. AB - The actions of zinc ions on three species of K+ channels were studied using mouse fibroblasts stably transfected with a plasmid containing both the appropriate K+ channel gene and a steroid-inducible promotor. The channels studied were rKv1.1 and hKv1.5, delayed rectifiers cloned from rat and human tissue, respectively, and hKv1.4, an inactivating human K+ channel. Zn2+ shifted the activation curves for all three K+ currents in the depolarizing direction and also shifted the steady state inactivation curve for hKv1.4 in the depolarizing direction. The effect of Zn2+ was concentration dependent between 2 and 1000 microM. As a consequence of the modulation of gating, the activation kinetics of the K+ currents were slowed by Zn2+, an effect likely to delay repolarization of the neuronal action potential. The action of Zn2+ on these diverse K+ channels suggests the existence of a common Zn2+ binding domain, the occupation of which influences the voltage sensor. The resulting modulation of gating of hKv1.4 by Zn2+ may well be of physiological significance, in view of the localization of this channel in mossy fiber nerve terminals in the hippocampus, where Zn2+ is found in abundance. PMID- 8450838 TI - Evidence of stimulation of the gamma-aminobutyric acid shunt by valproate and E delta 2-valproate in neonatal rat brain. AB - The effect of valproate and its more active metabolite E-delta 2-valproate on the rate of glucose oxidation through different metabolic pathways in neonatal rat brain slices was studied. The presence of valproate or E-delta 2-valproate did not change the rate of [3,4-14C]glucose or [6-14C]glucose incorporation into CO2, suggesting that glucose oxidation through the pyruvate dehydrogenase-catalyzed reaction and through the tricarboxylic acid cycle was not affected by these drugs. However, both drugs significantly enhanced the rate of [2-14C]glucose oxidation, supporting the notion that the activity of the gamma-aminobutyric acid (GABA) shunt is specifically stimulated by valproate and, to a greater extent, by E-delta 2-valproate. The presence of methionine sulfoximine or gamma hydroxybutyrate did not change the GABA shunt activity. Brain glutamate decarboxylase activity was significantly increased after incubation of the brain slices in the presence of valproate. Consequently, our results suggest that the mechanism of action of valproate is related to the increase in the levels of the inhibitory neurotransmitter GABA caused by the enhancement of flux through the glutamate decarboxylase-catalyzed reaction. PMID- 8450839 TI - Cisplatin inhibits in vitro translation by preventing the formation of complete initiation complex. AB - We previously reported that mRNA loses the ability to direct in vitro peptide synthesis after incubation with cisplatin. The present study was designed to determine the step in translation that is affected. The rates of translation reactions inhibited by cisplatin were biphasic, having an initial rate comparable to that of the uninhibited reaction before decreasing. Analysis of cisplatin inhibited reactions in sucrose density gradients showed a decrease in polyribosome formation. These results are consistent with an inhibition of the initiation step of protein synthesis. Individual steps in initiation were tested by analyzing the formation of ribosomal subunits in sucrose gradients that resolve the incomplete complexes. Cisplatin caused an accumulation of 48 S particles accompanied by a decreased amount of completed 80 S initiation complexes. Similar results were obtained in experiments utilizing radiolabeled methionine or mRNA. We conclude that cisplatin blocks the initiation of translation by preventing the joining of the 60 S ribosomal subunit to the 48 S preinitiation subunit. PMID- 8450840 TI - Epidemiology of clinical allergy. Introduction. PMID- 8450841 TI - Epidemiology of allergic occupational lung disease. PMID- 8450842 TI - Epidemiology of food sensitivity in childhood--with special reference to cow's milk allergy in infancy. PMID- 8450843 TI - Epidemiology of insect sting allergy. PMID- 8450844 TI - Epidemiology of allergic drug reactions. PMID- 8450845 TI - Genetic aspects of atopy. PMID- 8450846 TI - Factors which promote or prevent allergy. PMID- 8450847 TI - Epidemiology of contact dermatitis. PMID- 8450848 TI - Epidemiology of urticaria. PMID- 8450849 TI - Epidemiology of allergic rhinitis. PMID- 8450850 TI - Epidemiology of asthma. PMID- 8450851 TI - The epidemiology of atopic dermatitis. PMID- 8450852 TI - Brief report: disseminated osteomyelitis from Mycobacterium ulcerans after a snakebite. PMID- 8450853 TI - Giardia Lamblia. PMID- 8450854 TI - Physicians' perspectives on caring for patients in the United States, Canada, and West Germany. AB - BACKGROUND: The United States is considering enacting a national health plan and global health care budget similar to those in other countries. There are few data on the effects of such policies on physicians and patients. METHODS: We conducted a telephone survey of 602 physicians in the United States, 507 physicians in Canada, and 519 physicians in the former West Germany from February through May 1991; the response rates were 44 percent, 49 percent, and 41 percent, respectively. Among other topics, the questionnaire included measures of satisfaction with the health care system and with medical practice. RESULTS: In the United States, 23 percent of the physicians surveyed thought the health care system worked well, as compared with 33 percent in Canada and 48 percent in West Germany. Seventy-three percent of U.S. physicians reported that patients' inability to afford necessary treatment was a serious problem, as compared with 25 percent in Canada and 15 percent in West Germany. Seventy-seven percent of West Germany physicians, 56 percent of Canadian physicians, and 54 percent of U.S. physicians said the shortage of competent nurses was a serious problem. In Canada, 50 percent of the respondents cited the lack of well-equipped medical facilities as a problem, as compared with 14 percent in the United States and 20 percent in West Germany. CONCLUSIONS: Programs of universal coverage and cost containment necessitate important trade-offs. In Canada and West Germany, physicians do not report serious problems of access to care for the poor and uninsured. In the United States, doctors do not face the limited access to sophisticated forms of medical technology that was reported in Canada or the diminished quality of some services reported in West Germany. PMID- 8450855 TI - Management of chronic obstructive pulmonary disease. PMID- 8450856 TI - Treatment of non-Hodgkin's lymphoma. PMID- 8450857 TI - Right ventricular infarction. PMID- 8450858 TI - Attention deficit-hyperactivity disorder and resistance to thyroid hormone--a new idea? PMID- 8450859 TI - The Journal and SI units. PMID- 8450860 TI - The Journal and SI units. PMID- 8450861 TI - The Journal and SI units. PMID- 8450862 TI - The Journal and SI units. PMID- 8450863 TI - The Journal and SI units. PMID- 8450864 TI - Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation. PMID- 8450865 TI - Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation. PMID- 8450866 TI - A hypercoagulable state in the left atrium of patients with mitral stenosis. PMID- 8450867 TI - Bronchodilator therapy with or without inhaled corticosteroid therapy for obstructive airways disease. PMID- 8450868 TI - Bronchodilator therapy with or without inhaled corticosteroid therapy for obstructive airway disease. PMID- 8450869 TI - The consequences of testing for Huntington's disease. PMID- 8450870 TI - Malaria imported from Somalia. PMID- 8450871 TI - Antibiotics: too many names. PMID- 8450872 TI - Ending deaths from famine. The opportunity in Somalia. PMID- 8450873 TI - Starvation in the modern world. PMID- 8450874 TI - The threat of infectious diseases in Somalia. PMID- 8450875 TI - Right ventricular infarction as an independent predictor of prognosis after acute inferior myocardial infarction. AB - BACKGROUND: Acute inferior myocardial infarction frequently involves the right ventricle. We hypothesized that right ventricular involvement, as diagnosed by ST segment elevation in the right precordial lead V4R, may affect the prognosis of patients with inferior myocardial infarctions. METHODS: In 200 consecutive patients admitted to the hospital with acute inferior myocardial infarctions, we assessed the prevalence and diagnostic accuracy of ST-segment elevation in lead V4R (as compared with four other diagnostic procedures) to identify right ventricular involvement and its prognostic implications for in-hospital and long term outcomes. RESULTS: The in-hospital mortality after inferior myocardial infarction was 19 percent, and major complications occurred in 47 percent of the patients. The presence of ST-segment elevation in lead V4R in 107 patients (54 percent) was highly predictive of right ventricular infarction (sensitivity, 88 percent; specificity, 78 percent; diagnostic accuracy, 83 percent), as compared with the other diagnostic procedures. The patients with ST-segment elevation in lead V4R had a higher in-hospital mortality rate (31 percent vs. 6 percent, P < 0.001) and a higher incidence of major in-hospital complications (64 percent vs. 28 percent, P < 0.001) than did those without ST-elevation in V4R. Multiple logistic-regression analysis showed ST elevation in V4R to be independent of and superior to all other clinical variables available on admission for the prediction of in-hospital mortality (relative risk, 7.7; 95 percent confidence interval, 2.6 to 23) and major complications (relative risk, 4.7; 95 percent confidence interval, 2.4 to 9). The post-hospital course (follow-up, at least 1 year; mean follow-up, 37 months) was similar in patients with and in those without electrocardiographic evidence of right ventricular infarction. CONCLUSIONS: Right ventricular involvement during acute inferior myocardial infarction can be accurately diagnosed by the presence of ST-segment elevation in lead V4R, a finding that is a strong, independent predictor of major complications and in-hospital mortality. Electrocardiographic assessment of right ventricular infarction should be routinely performed in all patients with acute inferior myocardial infarctions. PMID- 8450876 TI - A defective visual pathway in children with reading disability. AB - BACKGROUND: The possibility that reading disability in children is associated with visual problems is in dispute. We sought to test the existence of this association by using electrophysiologic techniques to measure the processing of visual information in the magnicellular and parvicellular visual pathways of the brain. METHODS: Visual evoked potentials were measured with scalp electrodes in children 8 to 11 years old who were normal readers and in those with reading disability. The potentials were measured for targets with low (0.5 cycle per degree of visual angle) and high (4.5 cycles per degree) spatial frequency, surrounded by either a steady background or a uniform-field flickering 12 times per second. A flickering field normally reduces the amplitude and increases the latency of a transient potential evoked by a low-spatial-frequency target, which preferentially excites the magnicellular visual pathway, but has little effect on the response to a high-spatial-frequency target. RESULTS: With a steady background, the latencies of the early components (N1 and P1) of the visual evoked potentials were longer in the reading-disabled children than in the normal readers when the low-spatial-frequency target was used, but not when the high spatial-frequency target was used. In normal readers, the flickering background increased the latency and reduced the amplitude of the early components, whereas in the reading-disabled children only the amplitude was affected. No differences were observed in either group with the high-spatial-frequency target. CONCLUSIONS: The pattern of results suggests that the response of the magnicellular visual pathway is slowed in reading-disabled children, who do not, however, have a general slowing of the visual response. The possibility that there is a cause-and-effect relation between these findings and reading disability will require further study. PMID- 8450877 TI - Attention deficit-hyperactivity disorder in people with generalized resistance to thyroid hormone. AB - BACKGROUND: Attention deficit-hyperactivity disorder is a well-recognized psychiatric disorder of childhood. Its cause is unknown, but there is evidence of a familial predisposition. Symptoms suggestive of this disorder have been reported in subjects with generalized resistance to thyroid hormone, a disease caused by mutations in the thyroid receptor-beta gene and characterized by reduced responsiveness of peripheral and pituitary tissues to the actions of thyroid hormone. We systematically evaluated the presence and severity of attention deficit-hyperactivity disorder in 18 families with a history of generalized resistance to thyroid hormone. METHODS: We studied 49 affected and 55 unaffected family members; 52 were adults, and 52 were children. All subjects were evaluated with structured psychiatric questionnaires by interviewers who were unaware of the medical diagnosis. The number of symptoms of attention deficit-hyperactivity disorder was calculated for each subject. RESULTS: Among the adults, 11 of 22 subjects with generalized resistance to thyroid hormone (50 percent) and 2 of 30 unaffected subjects (7 percent) had met the criteria for attention deficit-hyperactivity disorder as children (P < 0.001). Among the children, 19 of 27 subjects resistant to thyroid hormone (70 percent) and 5 of 25 unaffected subjects (20 percent) met the criteria for the disorder (P < 0.001). The odds of having attention deficit-hyperactivity disorder were 3.2 times higher for affected male subjects than for affected female subjects and were 2.7 times higher for unaffected male subjects than for unaffected female subjects. The mean symptom score was 2.5 times higher in the affected group than in the unaffected group (7.0 vs. 2.8, P < 0.001). The frequency of other psychiatric diagnoses was similar in the two groups. CONCLUSIONS: In our study sample, attention deficit hyperactivity disorder is strongly associated with generalized resistance to thyroid hormone. PMID- 8450878 TI - Consent laws. PMID- 8450879 TI - Watson, Crick and the future of DNA. PMID- 8450880 TI - Potassium channels. Advent of a new family. PMID- 8450882 TI - Archaeology. 50,000-year-old Americans of Pedra Furada. PMID- 8450881 TI - Transcription. The omnipotent nucleosome. PMID- 8450883 TI - Psychology. Weighing of the talents. PMID- 8450884 TI - Lipid diffusion in neurons. PMID- 8450885 TI - Inside information. PMID- 8450886 TI - The torso receptor localizes as well as transduces the spatial signal specifying terminal body pattern in Drosophila. AB - Specification of the end portions of the Drosophila body depends on the torso (tor) protein, a receptor tyrosine kinase that accumulates uniformly along the entire surface of the embryo but is activated only in the vicinity of the poles. Several genes are normally required for activating tor and appear to define a system in which a gene product tethered to the extracellular vitelline membrane at each end of the egg provides a local source for an extracellular tor ligand. This ligand would have to diffuse from the membrane to the cell surface of the embryo without losing its spatial localization. Here we report that the failure to accumulate tor protein at one or both poles leads to spatially inappropriate activity of more centrally located receptor. This ectopic activity depends on the same gene functions normally required for activating tor; thus we infer that it reflects inappropriate diffusion of the ligand to more central regions of the body. We conclude that the receptor not only transduces the spatial signal imparted by the tor ligand, but also ensures its correct localization by sequestering the ligand. Ligand trapping by receptor may also localize spatial signals in other patterning systems, including specification of the dorsal ventral axis in Drosophila and of vulval cell fates in Caenorhabditis elegans. PMID- 8450887 TI - Principles of locomotion for simple-shaped cells. AB - Moving cells display a variety of shapes and modes of locomotion, but it is not clear how motility at the molecular level relates to the locomotion of a whole cell, a problem compounded in studies of cells with complex shapes. A striking feature of fish epidermal keratocyte locomotion is its apparent simplicity. Here we present a kinematic description of locomotion which is consistent with the semicircular shape and persistent 'gliding' motion of fish epidermal keratocytes. We propose that extension of the front and retraction of the rear of these cells occurs perpendicularly to the cell edge, and that a graded distribution of extension and retraction rates along the cell margin maintains cell shape and size during locomotion. Evidence for this description is provided by the predicted circumferential motion of lamellar features and the curvature of 'photo marked' lines within specific molecular components of moving keratocytes. Our description relates the dynamics of molecular assemblies to the movement of a whole cell. PMID- 8450888 TI - The p250 subunit of native TATA box-binding factor TFIID is the cell-cycle regulatory protein CCG1. AB - The protein TFIID is a general transcription factor which initiates preinitiation complex assembly through direct interaction with the TATA promoter element. It is a multisubunit complex containing a small TATA-binding polypeptide (TBP) and other TBP-associated factors (TAFs) ranging in size from about 30-250K (refs 7 10). Although native TFIID can mediate both activator-independent (basal) and activator-dependent transcription in reconstituted systems, TBP itself can mediate only basal transcription, even in cases where TBP or the general factor TFIIB are known to interact directly with transcriptional activators. TFIID subunits other than TBP must therefore be essential cofactors, and thus potential targets for activators, consistent with earlier demonstrations that activators interact with TFIID (refs 3, 5, 16, 17). Here we show that the 250K subunit of TFIID is identical to a gene product previously implicated in progression through the late G1 phase of the cell cycle. Part of p250 may thus serve a specific function in the activation of a subset of genes important for cell cycle progression. PMID- 8450890 TI - Women at NIH trail men in salaries and tenure. PMID- 8450889 TI - Yeast tRNA(Asp) recognition by its cognate class II aminoacyl-tRNA synthetase. AB - Aminoacyl-RNA synthetases can be divided into two classes according to structural features inferred from sequence alignments. This classification correlates almost perfectly with the attachment of the amino acid to the 2'-OH (class I) or 3'-OH (class II) group of the terminal adenosine. Six subgroups of higher homology can be inferred from sequence analysis. The five aminoacyl-tRNA synthetases whose crystal structures are known (MetRS, TyrRS and GlnRS in class I, SerRS and AspRS in class II) belong to different subgroups. Two of them, GlnRS and AspRS, have been cocrystallized with their cognate tRNA. AspRS, like six other members of class II, is an alpha 2 dimer. Yeast tRNA(Asp) exhibits five identity determinants: the three anticodon bases, the discriminator base G73 and the base pair G10-U25. We report here that the refined crystal structure of AspRS complexed with tRNA(Asp) at 2.9 A resolution reveals three regions of contact, each involving a domain of AspRS and at least one identity determinant of tRNA(Asp). The mode of binding of the acceptor stem of tRNA(Asp) by AspRS can be generalized to class II aminoacyl-tRNA synthetases, whereas the deciphering of the anticodon, which involves a large conformational change of the loop and the formation of a bulge, is more specific to the aspartic system. PMID- 8450891 TI - [Brain metastases as an initial manifestation of tumor disease]. AB - A retrospective study compared a group of 122 patients with brain metastases from unknown primaries with a second group of 121 patients, who developed brain metastases in the course of a known malignant disease. Special attention was paid to the kind of primary cancer, therapeutic influences and prognostic differences. The results pointed to a late occurrence of brain metastases in breast cancer, no patient with this type of cancer being found in group 1. Melanoma and colorectal cancer were also found predominantly in group 2, whereas lung cancer was the most common cause of metastasis in group 1 and the most frequent cancer in both groups. Clinical course, therapy and outcome showed no significant differences between the two groups. Mean survival time was 4.6 (+/- 6) months for the patient series as a whole. Patients with breast cancer had a significantly higher survival rate than those with other forms of cancer. Localisation and degree of malignancy mainly determine the life-prognosis, the type and intensity of therapy being of secondary importance. PMID- 8450892 TI - [Stereotactic interstitial radiosurgery and percutaneous radiotherapy in treatment of cerebral metastases]. AB - The efficacy of interstitial radiosurgery as an alternative or adjuvant to radiotherapy or surgery of cerebral metastases remains unclear. In a retrospective study (1982-1991) we compared 4 therapeutic regimes for cerebral metastases. The first group (n = 38) was treated with interstitial radiosurgery (Iodine-125) with a tumor dose of 60 Gy in combination with percutaneous radiotherapy with 40 Gy. The second group was treated by interstitial radiosurgery alone (n = 22) (tumor dose: 60 Gy). The third group was treated with percutaneous radiotherapy alone with a total dose of 40 Gy (n = 49). The fourth group (n = 21) consisted of recurrent cerebral metastases which were treated by interstitial radiosurgery alone (tumor dose: 60 Gy). Interstitial radiosurgery was performed in cases of circumscribed mostly solitary metastases < or = 5 cm in diameter. Medium survival was 17 months after interstitial radiosurgery in combination with radiotherapy, 12 months after radiosurgery alone and 7.7 months after percutaneous radiotherapy. The medium survival of recurrent metastases after interstitial radiosurgery was 6 months. Prognostically favourable for the outcome following radiosurgery were a Karnofsky Score > or = 70, a solitary metastasis, absence of disseminated disease and a longer time interval between diagnosis of the primary and diagnosis of the cerebral metastases. Interstitial radiosurgery + percutaneous radiotherapy was not superior to interstitial radiosurgery alone in the multivariate analysis. No patient died from a locally treated metastasis. Percutaneous radiotherapy was the treatment of choice for multiple or non-circumscribed cerebral metastases. Our results show that for solitary metastases stereotactic interstitial radiosurgery is a beneficial minimally invasive method. PMID- 8450893 TI - [Effectiveness and tolerance of amitriptyline oxide in chronic tension headache- a multicenter double-blind study versus amitriptyline versus placebo]. AB - Tricyclic antidepressants, especially amitriptyline, are the medication of first choice in the treatment of chronic tension headache. Few previous studies meet modern standards of study design and statistical analysis. Tolerability and efficacy of 60-90 mg amitriptyline oxide (AO) as a single dose in the evening were compared with 50-75 mg amitriptyline (AM) and placebo (PL) in a double blind, parallel-group trial consisting of a 4-week baseline phase and 12 weeks of treatment. The 3-armed study was conducted in 7 centers. The inclusion criterion was tension-type headache on at least 15 days monthly with a duration of at least 6 months. Exclusion criteria were a migraine history, previous participation in another clinical trial within the last 3 months, drug abuse, medication with other antidepressants or tranquilizers, current use of other acknowledged prophylactic headache medication, lack of compliance, major psychiatric disorder according to DSM-III and medical contra-indications against tricyclic antidepressants. The primary study endpoint was a reduction at least 50% of the product of headache duration and frequency and a reduction at least 50% in headache intensity. Statistics used were Fisher's Exact Test and an analysis of variance. A total of 211 patients were included in this trial. One hundred ninety seven cases, 87 males and 110 females, with a mean age of 38 +/- 13 (18-68) years, could be analysed completely (66 AO, 67 AM, 64 PL). With regard to the strictly defined primary study endpoint, no significant difference emerged between AO, AM and PL: treatment responders were 30.3% with AO, 22.4% with AM and 21.9% with PL (PAO-PL = 0.3210, PAM-PL = 1.000, PAO-AM = 0.3299 respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450894 TI - [Migraine: differential diagnosis in episodic vertigo]. AB - Vestibular symptoms can be the predominant feature of migraine both in children and adults. Attacks of spontaneous or positional vertigo lasting from minutes to days may occur with or without concomitant headache. In the literature three syndromes of vestibular migraine have evolved: basilar artery migraine, benign recurrent vertigo and benign recurrent vertigo of childhood. In clinical practice, however, variants seem to be more frequent than the pure syndromes. Diagnosis is based on the individual constellation of typical precipitants and symptoms of migraine and the efficacy of pharmacological migraine prophylaxis. Nine cases are presented. PMID- 8450895 TI - [A special case of frontal lobe epilepsy]. AB - We present clinical, electrophysiological and neuropsychological data of a patient with an extraordinary type of frontal lobe epilepsy. In addition to complex partial and secondary generalized seizures the patient had 183 non convulsive states per day. Chronical electrocorticography via subdural electrodes clearly revealed that the complex partial seizures and the secondary generalized seizures originated within the right frontal lobe. During the non-convulsive states a constantly increasing spike frequency which showed characteristics of secondary bilateral synchrony was noticed within both frontal lobes. After a period of 20-40 min a sudden transition into a clinically generalized seizure occurred. In contrast to the clinical generalization the onset of bilateral motor phenomena was paralleled by a "secondary focalisation" of the pre-existent high frequency interictal bifrontal epileptiform activity within the right frontal lobe. PMID- 8450896 TI - [Thalamic form of Creutzfeldt-Jakob disease]. AB - We report a patient presenting with rapid progressive dementia. Neuropathological findings indicative for Creutzfeldt-Jakob disease--vacuolisation, nerve cell loss and gliosis--were found isolated in the thalamus and the basal ganglia. Clinical, neurophysiological and pathological findings in thalamic form of Creutzfeldt Jakob disease differentiate significantly to other forms of Creutzfeldt-Jakob disease. PMID- 8450897 TI - [Clinico-genetic diagnosis of ataxia telangiectatica (Louis-Bar syndrome)]. AB - We describe the possible difficulties in getting the diagnosis "ataxia telangiectasia" using the example of a 16 years old girl. If cases of cerebellar ataxia in childhood present without classical symptoms, the diagnosis of ataxia telangiectasia should not be excluded before chromosome analysis. In our case, first signs of cerebellar ataxia were observed from the age of 11 years and we found only mild, atypical located and late onset telangiectasis. Other signs of the syndrome, such as elevated alpha-fetoproteine and deficiency of IgA or IgE could not be detected. Chromosome analysis, however, demonstrated a breakage syndrome with chromosome 14 to 7 translocation and established a firm diagnosis of ataxia telangiectasia. Patients with chromosome breakage syndromes including the Louis-Bar-syndrome have an increased risk for malignomas. Therefore chromosome analysis should be undertaken in cases of children with cerebellar ataxia, and frequent radiological examination avoided. PMID- 8450898 TI - [Search movements of the tongue in speech apraxia: imaging with ultrasound and pseudo-3D reconstruction]. PMID- 8450899 TI - [HIV encephalopathy--clinical aspects, neuropathology and pathogenesis]. AB - HIV encephalopathy, which is probably primarily caused by human immunodeficiency virus, is the most common neurological disorder in HIV-infected patients and is more frequent than opportunistic diseases of the central nervous system. It is characterized most often by slowly progressing cognitive impairment, psychomotoric slowing and increasing apathy. The syndrome is found almost exclusively in the late stages of HIV infection; its frequency in patients with full-blown AIDS is estimated as being between 40 and 70%. Although numerous studies have demonstrated alterations in the electrophysiological parameters, cerebral perfusion and cerebrospinal fluid in many asymptomatic patients, there are no reliable parameters that can predict the risk of developing HIV encephalopathy. Also, there is no sufficient correlation between the extent of the frequent but mostly subtle neuropathological changes and the clinical degree of the severity of the encephalopathy. The mechanisms causing cerebral injury are poorly understood. Recent studies indicate that the indirect effects of HIV infection of the brain are the most important pathogenetic factors. In particular, certain viral proteins and cytokines produced by infected macrophages or activated microglia seem to induce neuronal dysfunction and finally loss of nerve cells. PMID- 8450900 TI - [Immunoglobulin therapy of neuromuscular diseases]. AB - High-dose intravenous immunoglobulin (IVIG) is effective in myasthenia gravis (MG), Guillain-Barre syndrome (GBS), and chronic inflammatory polyneuropathy (CIDP). The effect is equivalent to plasmapheresis (PE), and in GBS perhaps superior. IVIG may be effective, even if PE or corticosteroids have been ineffective -- and vice versa. IVIG may well become the therapy of first choice in MG, GBS, and CIDP as it is easily administered, there are no serious side effects and there exists no risk of virus transmission. Future studies will show if a combination of PE and IVIG is superior to either of the two treatment schedules alone. PMID- 8450901 TI - [Experiences with high dosage immunoglobulin G in neuromuscular diseases]. AB - High-dose intravenous immunoglobulin G (IVIG) was used as alternative treatment in 39 patients with crisis in myasthenia gravis (MG), acute polyneuritis (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP). Of 10 patients with MG, 3 recovered completely, 5 patients improved except for long-standing ocular signs, 1 patient was weaned from artificial ventilation, and one patient did not improve after IVIG, but did so after plasma exchange. 25 GBS patients were treated with IVIG, progression of weakness was stopped in 24; 12 showed complete or near complete recovery and 6 improved markedly. Of 4 patients with CIDP, 2 responded definitely. The majority of patients with MG, GBS, CIDP, respond to IVIG treatment. The effect seems to be equivalent to plasma exchange. In GBS, IVIG may be superior. Side effects of IVIG are negligible, and there is no risk of transmission of AIDS-, hepatitis-, or other viruses. PMID- 8450902 TI - Uremia and infection: mechanisms of impaired cellular host defense. PMID- 8450903 TI - Gastrointestinal bleeding in dialysis patients. PMID- 8450904 TI - Hypertension in primary chronic glomerulonephritis analysis of 359 cases. AB - The incidence of hypertension was evaluated in 359 patients with primary chronic glomerulonephritis who underwent renal biopsy. It was compared to a control group of 7,468 subjects who were obtained from an epidemiologic study performed in the same area at the same period. The prevalence of hypertension was 42%. On the basis of multiple regression analysis, the level of blood pressure was shown to be positively correlated to four independent variables: age, body mass index, degree of renal insufficiency and presence of proliferative glomerulonephritis. It was concluded that, although renal insufficiency increases the incidence of hypertension, proliferative lesions play an important contributive role in the development of hypertension. PMID- 8450905 TI - Left ventricular diastolic impairment in type 1 diabetic patients with microalbuminuria. AB - The high incidence of cardiac mortality in type 1 diabetic patients is further increased when diabetic nephropathy is present. Since microalbuminuria (albumin excretion rate > 30 mg/day) represents an incipient stage of diabetic nephropathy, we decided to investigate whether incipient renal changes correlate with early diastolic cardiac dysfunction, known to preceed systolic dysfunction. To test this hypothesis, 13 normotensive type 1 diabetics with incipient nephropathy (mean age 37.8 +/- 3.5, diabetes duration 18.8 +/- 2.6 years), 13 type 1 diabetics without nephropathy (matched for age, diabetes duration and metabolic control) or other microangiopathic changes and 13 normal controls were studied. Diseases known to affect left ventricular performance were ruled out before investigation. Right and left ventricular parameters were assessed by M mode and Doppler echocardiography. While parameters for left ventricular systolic function stayed within the normal range and did not differ between the two diabetic groups (ejection fraction 69.3 +/- 2.4 vs. 69.6 +/- 1.4%; fractional shortening 40.3 +/- 2.2 vs. 38.5 +/- 1.1%), diastolic function was significantly impaired in diabetic patients with microalbuminuria. This is expressed by an inversed early and late peak flow velocity ratio in patients with microalbuminuria (0.988 +/- 0.04 vs. 1.362 +/- 0.1; p < 0.05) and a significant percentual increase in late (atrial) filling (39.1 +/- 1.7 vs. 29.9 +/- 1.4% when compared to whole filling; p < 0.05) despite a similar rate-corrected isovolumetric relaxation period in both diabetic groups (98.4 +/- 5.8 vs. 95.5 +/ 6.2).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450906 TI - Direct effect of deferoxamine on hemoglobin synthesis in patients on hemodialysis treated with recombinant human erythropoietin. AB - We have studied the response of hemoglobin (Hb), hematocrit, reticulocytes, mean corpuscular volume, ferritin, serum iron, total iron-binding capacity (TIBC) and the transferrin saturation index in 9 patients on chronic hemodialysis (HD) with minimal aluminum overload who were treated with recombinant human erythropoietin (rHuEPO) when a single dose of deferoxamine (DFO; 40 mg/kg b.w.) was administered. Analytical determinations were performed basally and 48 h, 7 days and 14 days after a DFO test. Hb increased from a basal value of 10 +/- 0.28 to 10.7 +/- 0.33 (p < 0.05), 10.4 +/- 0.33 (p < 0.05) and 10.1 +/- 0.31 g/dl (NS), respectively, and similar increases were seen with the hematocrit. Serum iron increased from 52 +/- 7.62 to 89.2 +/- 14.48 (p < 0.01), 94 +/- 18.73 (p < 0.01) and 85 +/- 14.01 micrograms/dl (p < 0.01), respectively. TIBC and ferritin did not change but the transferrin saturation index increased significantly. DFO produces an immediate improvement of the anemia in HD patients treated with rHuEPO and who have minimal aluminium accumulation: it should be related to an increased iron availability to erythroid precursors either releasing stored iron or decreasing aluminum-bound transferrin. PMID- 8450907 TI - Idiopathic adult focal segmental glomerulosclerosis: a clinicopathological study and response to steroid. AB - A total of 65 adult cases (53 males, 12 females) with biopsy-proven focal segmental glomerulosclerosis (FSGS) were studied. Hypertension, ascites and haematuria were seen in 13, 12 and 24 cases, respectively. Decreased creatinine clearance at presentation was found in 9 cases. Mean proteinuria per day, serum cholesterol and total protein were 7.5 +/- 4.3 g, 388.95 +/- 213.4 mg% (10.11 +/- 5.55 mmol/l) and 5.27 +/- 1.1 g% (0.527 +/- 0.11 milligram), respectively. Mesangial proliferation was seen in 13 cases and hilar sclerosis in 5. Fifty percent showed positive immunofluorescence; IgM in 10, C3 in 8, and IgG in 2. Forty-two cases could be followed (mean 32 months), out of which 38 had nephrotic syndrome and were treated with prednisolone; 58% showed response (31% complete remission and 27% partial remission). One patient in each group of responders and nonresponders had renal failure at the end of follow-up. Hypertension, degree of proteinuria, mesangial proliferation, degree of tubular atrophy and immunofluorescence findings did not significantly affect the response to steroids. We conclude that a group of patients with idiopathic adult FSGS has a favourable response to steroids, which cannot be predicted clinically. PMID- 8450908 TI - Renal hypouricemia and absorptive hypercalciuria: a real syndrome. AB - We describe a case of renal hypouricemia due to increased tubular secretion of urate associated with absorptive hypercalciuria. This association has been described in the past, but this is the first time that high plasma levels of 1,25 dihydroxyvitamin D have been reported. A possible cause-and-effect relation between altered uric acid transport and altered vitamin D metabolism in the proximal tubule is suggested. PMID- 8450909 TI - Fine structure of calcium oxalate monohydrate renal calculi. AB - Fine structure, location and size of the core of 12 calcium oxalate monohydrate (COM) papillar calculi from different 'idiopathic' stone-formers were studied by an optical and scanning electron microscope equipped with the EDAX analytical device. Each individual core exhibited a unique overall structure composed of loosely arranged twined and intergrown crystals of plate-like and/or columnar shape and particles of 'rosette' structure with considerable void space among crystals in some cases or compact structure in others. Crystals were covered by a thin layer or organic material mostly invisible to the microscope. Sometimes debris of organic origin in a core was observed. A substantial amount of organic matrix appeared at the core boundary, often in the form of amorphous plates. The outer striated layer of COM stone consisting of tightly packed columnar crystals originated on this matrix. The stone core was located near the stone surface that was attached to the kidney wall and contained foreign particles that act as heterogeneous nucleants of calcium oxalate crystals. PMID- 8450910 TI - A case of collagenofibrotic glomerulopathy associated with hepatic perisinusoidal fibrosis. AB - A patient with collagenofibrotic glomerulopathy associated with hepatic persinusoidal fibrosis is described. Renal biopsy revealed that the glomerular tufts contained homogeneous material that was proved by electron microscopy to be collagen fibers. The material was reactive to anti-type III collagen monoclonal antibody. Liver biopsy also showed an increase of type III collagen fibers in the perisinusoidal area. Since the serum procollagen III peptide level was elevated in this patient, fibrosis may have been simultaneously activated in kidney and liver by some unknown condition. PMID- 8450911 TI - Fibrinolytic activity in end-stage renal disease. AB - Recently, we described that in the physiologic state, urokinase concentration is higher in the renal vein than in the renal artery which suggests that the kidney is the essential organ providing urokinase to the systemic circulation. In end stage renal disease (ESRD) patients, urokinase provided by the kidney may be decreased, and this might be the cause of decreased systemic fibrinolytic activity seen in ESRD. To study this possibility, we measured fibrinolytic profiles including urokinase, tissue plasminogen activator (t-PA) and fibrinolytic activity in the euglobulin fraction of ESRD patients and compared the results with those of two control groups consisting of renal transplantation patients and age- and sex-matched healthy controls. The euglobulin fibrinolytic activity was 92.2 +/- 14.8 BAU in the ESRD group, 108.7 +/- 13.5 BAU in the kidney transplantation (KT) group and 101.5 +/- 8.0 BAU in the healthy control group. Although it was lower in the ESRD than in the KT (p < 0.005) and the healthy control group (p < 0.005), there was no difference between the KT and the healthy control group. t-PA antigen was 1.2 +/- 1.3 ng/ml in the ESRD group, 3.5 +/- 1.7 ng/ml in the KT group and 3.1 +/- 2.1 ng/ml in the healthy control group. It was lower in the ESRD compared to the KT (p < 0.001) and the healthy control group (p < 0.001) but there was no difference between the KT and the healthy control group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450912 TI - Interstrain differences in murine daunomycin-induced nephrosis. AB - Examining 8 inbred murine strains [A/J, BALB/c, SM/J, C3H/J, SWR/J, C57BL/6J (B6), DBA-2, B10D2/old (B10D2/o)] for urinary albumin excretion after a single daunomycin (DM) injection (20 mg/kg), we found strain specificity in susceptibility to DM nephrosis. This specificity did not relate to the serum disappearance rate of this drug. A/J and BALB/c were highly susceptible to the nephrosis while C57BL/6J, DBA-2 and B10D2/o were completely resistant to it. Chronological observation revealed that A/J mice had significant proteinuria at 2 weeks after injection, and it persisted for the remaining 4 weeks of this experiment, while C57BL/6J showed no increase over the experimental period. Using segregants obtained from an A/J and B6 backcross, it has been shown that susceptibility is inherited as an autosomal recessive trait and involves approximately three genes. Neither a C5 deficiency, H-2 type nor coat color gene (c-locus) was related to this susceptibility. This strain difference in nephrotoxicity would be a promising way to investigate its subcellular mechanism. PMID- 8450913 TI - Effect of oxygen tension on activity of antioxidant enzymes and on renal function of the postischemic reperfused rat kidney. AB - The aim of the present study was to examine the effect of exposing animals to 100% oxygen instead of room air on renal function and endogenous antioxidant enzymes of the postischemic reperfused rat kidney. Superoxide dismutase (SOD), catalase and glutathione peroxidase (GPX) were determined in the homogenate of the left kidney after 45 min of ischemia, caused by clamping the left renal artery, 10 and 90 min after reperfusion while the animals breathed room air or 100% O2. The right kidney served as a control. The possible influence of trapped blood in the clamped kidney was also investigated by the use of a correction factor based on the Hb concentration in the homogenate. The results indicate that such correction is necessary as the blood adds significant antioxidant activity. The activities of all 3 enzymes after 45 min of ischemia decreased significantly in the left (ischemic) compared to the right (control) kidney, to 64% of the control levels for catalase, 58% for SOD and 49% for GPX. After 10 min of reflow, a further decrease in the activities of catalase (to 49%) and of GPX (to 29%) was found. SOD activity, however, increased to 64%. After 90 min of reperfusion, restoration toward normal levels was noticed (SOD activity increased to 70%, catalase to 76% and GPX to 58%). Breathing 100% O2 resulted in a significant decrease in all enzyme activities (to 38.6% for catalase, 45% for SOD and to 27.4% for GPX). This inactivation can be explained by increased reactive oxygen species (ROS) activity during hyperoxia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450915 TI - Hemodialysis for treatment of accidental hypothermia. AB - Accidental hypothermia is defined as a spontaneous decrease in core temperature to 35 degrees C or below. Several techniques of active core rewarming have been described. We present the case of a 34-year-old man with severe hypothermia (27 degrees C) caused by cold environment exposure and barbiturate intoxication treated with general supportive measures and active core rewarming with hemodialysis. Core temperature increased by 2.15 degrees C/h with hemodialysis and became normal in 4 h. The clinical situation clearly improved during the hemodialysis session and the patient recovered without any defect. Hemodialysis is a rapid and effective treatment for accidental hypothermia. PMID- 8450914 TI - Effects of heat therapy on renal hemodynamics, compensatory hypertrophy and glomerulonephritis in rats. AB - To investigate whether back heating (BH) affects renal function, we applied an electric heating pad on the back skin overlying the kidneys in rats. In the acute experiment on saline-expanded, normal conscious rats, BH up to 42 +/- 1 degrees C for 15 min induced diuresis, natriuresis, kalliuresis, increased urinary kallikrein excretion as well as an increase in renal blood and plasma flow and glomerular filtration rate (GFR). When the rats were uninephrectomized and subjected to either BH twice a day for 1 week or a sham procedure, the study group showed a higher GFR per gram kidney weight and a higher increase in kidney/body weight ratio. When the rats were injected daily with cationic bovine serum albumin for 30 days and then subjected to either BH twice a day for 26 days or a sham procedure, the BH group showed a higher degree of proteinuria during the recovery period and a higher kidney/body weight ratio on the 27th day. Acute BH for 15 min in anesthetized rats increased body temperature, perirenal temperature, heart rate, stroke volume, cardiac output and cardiac index. Taken together, these results suggest that BH may affect the kidneys in normal and pathologic states. These effects may be at least partly related to a change in systemic hemodynamics. PMID- 8450916 TI - Long-term survival on renal replacement therapy for primary hyperoxaluria type I. AB - We describe the case of a patient in end-stage renal failure due to primary hyperoxaluria type I (PH1) who started hemodialysis in 1977 and is still alive and active. The diagnosis of PH1 was first suspected after a bone biopsy performed in 1981 to investigate hyperparathyroidism. Oxalosis recurred as early as 3 months after transplantation in a cadaver kidney grafted in 1987; nevertheless, graft function remained good enough to make possible the discontinuation of dialysis treatment for 5 months and thereafter to have only 1 dialysis a week for 17 months. The diagnosis of PH1 has been recently confirmed despite the patient being already anuric by means of the determination of plasma oxalate and glycolate levels as well as by determining hepatic alanine:glyoxylate amino-transferase. PMID- 8450917 TI - Demeclocycline-induced phosphate diabetes in a patient with inappropriate ADH secretion and systemic sarcoidosis. AB - We report a case of phosphate diabetes in a patient with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with sarcoidosis. Our patient was affected by systemic sarcoidosis and he fits the criteria of Schwartz for the diagnosis of SIADH. He presented with phosphate diabetes which appeared during demeclocycline (DMC) therapy and persisted for about 1 month from the end of DMC. It constitutes the fourth case of phosphate diabetes induced by tetracycline described in the literature and it is the third case of SIADH associated with sarcoidosis. PMID- 8450918 TI - Peroxidative modification of very-low-density lipoproteins in chronic hemodialysis patients. PMID- 8450919 TI - Bone marrow involvement in systemic amyloidosis: another mechanism for erythropoietin resistance. PMID- 8450920 TI - Essential mixed cryoglobulinemia and IgA nephropathy, an infrequent association. PMID- 8450921 TI - Plasma levels of branched chain keto acids in nephrotic patients. PMID- 8450922 TI - Hyperammonemic encephalopathy due to intravenous essential amino acid administration in a patient with renal insufficiency. PMID- 8450923 TI - Idiopathic membranous nephropathy in an Australian population: the incidence of thromboembolism and its impact on the natural history. PMID- 8450924 TI - Irreversible acute renal failure after extracorporeal shock-wave lithotripsy. PMID- 8450925 TI - Oral high dose of 1,25-dihydroxyvitamin D3 increases bone mineral content. PMID- 8450926 TI - Membranous nephropathy associated with chronic thyroiditis. PMID- 8450927 TI - Development of immunoglobulin A nephropathy in a kidney transplant in a patient with previous history of Henoch-Schonlein purpura glomerulonephritis. PMID- 8450928 TI - The role of cortical connectivity in Alzheimer's disease pathogenesis: a review and model system. AB - Here we review current evidence in support of the cortical disconnection/cortical connectivity model of Alzheimer disease (AD) pathogenesis, a model which predicts that one of the first events in AD is damage to the entorhinal cortex and/or subiculum resulting in the disconnection of the hippocampal formation and neocortex, and the subsequent progression of the disease in a stepwise fashion along cortico-cortical connections. Much of the evidence for this model has been obtained from studies involving the limbic system where investigators have demonstrated a precise correspondence between established patterns of connectivity and the degenerative changes associated with AD. In addition, some studies of the distribution of neuritic plaques (NP) and neuro-fibrillary tangles (NFT) in the neocortex and subcortical structures have yielded corroborative data. The validity of the cortical disconnection/connectivity model in the neocortex remains to be established or refuted. We propose that testing of this model can be accomplished with systematic studies of the laminar and regional distribution of NP and NFT in a series of sequentially interconnected cytoarchitectural regions that also form part of two functional hierarchies--the paralimbic and occipitotemporal visual systems. To adequately control for variation between brains affected by AD, it is imperative that such studies be conducted in a large but varied population of AD cases exhibiting differences in several variables, including clinical and/or neuropathological severity of the disease, temporal duration of the disease, and clinical/neuropsychological profile. We believe that further understanding of the relationship between characteristic AD pathology and intrinsic anatomico-functional circuits will contribute not only to our comprehension of AD pathogenesis but also to our general knowledge of the human brain. PMID- 8450929 TI - Age-related alterations in the properties of hippocampal pyramidal neurons among rat strains. AB - We compared age-related alterations in the electrophysiological and pharmacological properties of CA1 hippocampal pyramidal neurons in three strains of rats (Sprague-Dawley, Fisher 344, and Wistar) at 3-4 and 25-32 months of age, using the in vitro slice preparation. The most consistent age-related alterations in the properties of rat hippocampal neurons were: a decrease in membrane excitability, a decrease in the amplitude and duration of inhibitory postsynaptic potentials and a decreased sensitivity to the effect of the cholinergic agonist carbachol. In contrast, no consistent alterations in calcium-dependent events were observed in these strains of rats. The age-related changes in the duration of the afterhyperpolarizations (AHPs) were different (and even opposite) depending on the strain studied. Our results show that age-related changes observed in a given strain are not necessarily present in all strains of the same species. PMID- 8450930 TI - Activation of cerebral blood flow during a visuoperceptual task in patients with Alzheimer-type dementia. AB - Changes in regional cerebral blood flow (rCBF) associated with a face-matching task were examined using positron emission tomography (PET) and H2(15)O in 7 patients with mild-moderate dementia of the Alzheimer type (DAT) and in 8 healthy age-matched controls. rCBF was normalized to whole brain flow and pixel-by-pixel difference images were computed by contrasting flow during a control task to flow during face matching. Both patients and controls showed bilateral rCBF increases in occipitotemporal extrastriate cortex during face matching. The magnitude of these increases was not significantly different between the groups. In addition, the patients showed greater rCBF activation in regions of occipital and frontal cortex. These results show that early in the course of DAT, patients utilize extrastriate cortex to perform a visuoperceptual task, as do control subjects but also show rCBF increases in additional cortical areas. Activation of these additional areas of cortex in the patients may reflect an increased attentional load during face matching due to their reduced cognitive capacity. PMID- 8450931 TI - Neuroanatomical connections and specific regional vulnerability in Alzheimer's disease. PMID- 8450932 TI - On not-so-simple tests of simple hypotheses: a commentary on the review and model system by De Lacoste and White. PMID- 8450933 TI - Differential vulnerability, connectivity, and cell typology. PMID- 8450934 TI - A longitudinal study of reaction time performance in Long-Evans rats. AB - This study was undertaken to examine individual differences in the progression of age-related decline on a measure of sensorimotor function. Twenty-one adult rats were trained on a simple reaction time (RT) task and assessed every 6 weeks from 14.5 to 25 months of age. An overall slowing of RT latencies associated with chronological age was observed. However, some rats maintained a stable performance with age while others slowed considerably. Another measure within the RT task, accuracy of performance, appeared to represent a stable individual characteristic that was insensitive to the effects of age. However, no measure of performance on the RT task at 14.5 months of age predicted later impairment in RT latency. At the completion of longitudinal testing, spatial learning in the Morris water maze was assessed in these aged rats along with a young comparison group. The aged rats were impaired relative to young controls in locating the escape platform. Measures of cognitive function and sensorimotor function within the spatial task were, however, unrelated to slowing of RT latency. PMID- 8450935 TI - A comparison of the regulatory properties of striatal and cortical adenylate cyclase. AB - Biochemical properties of adenylate cyclase in striatal and cortical membranes have been analyzed in parallel with their regulation by cholinergic compounds. Striatal adenylate cyclase is more sensitive to forskolin, while the cortical enzyme is more stimulated by GTP. In the presence of GTP, more inhibition by acetylcholine is seen in the cortex than in the striatum. Acetylcholine inhibits striatal adenylate cyclase activity equally in the presence or absence of forskolin but has a diminished ability to inhibit forskolin-stimulated adenylate cyclase in the cortex. The greater sensitivity of cortical muscarinic receptor coupled adenylate cyclase to EGTA and calcium indicates predominant involvement of the calcium/calmodulin-dependent subtype of the enzyme. The relative effectiveness of antagonists, demonstrating an order of potency of atropine > amitriptyline > pirenzepine > gallamine in reversing the inhibition of adenylate cyclase by acetylcholine for both brain regions, suggests predominantly m4 receptor-mediated responses. These results suggest an m4-type receptor may be coupled to subtypes of adenylate cyclase in the striatum and cortex which differ in their biochemical properties. PMID- 8450936 TI - The pattern of age-related differences in electrophysiological activity of healthy males and females. AB - Age-related differences in quantified electrophysiological measures were examined in 202 subjects (109 females; 93 males) ages 30-80 all of whom were judged to be optimally healthy on a wide variety of criteria. The study utilized both absolute and relative measures from EEG spectral analysis as well as additional measures from long latency-evoked potentials. The same findings were noted for the 109 newly studied females as were reported for 63 previously studied male subjects. Results indicate that there is a broad trend for decreased EEG slow and increased fast activity with age, however, some of the measures change linearly and others are best represented by nonlinear functions. There is no decade where activities remain stable. Overall the pattern of change for males and females is similar, however, gender differences in both the EEG and EP data were present. The females had higher magnitudes for almost all absolute spectral and fast relative spectral measures. However, females demonstrated lower absolute alpha amplitude, lower relative slow activity, and lower late-latency EP data. Moreover, the absolute slow activity measure showed a gender X age interaction, indicating that the females had a different change in pattern of activity with increasing age than the males. Thus, gender-related findings were complex and could not be expressed as simple differences in overall amplitude. Age-related change is not a simple linear process but differs for differing EEG spectral bands, relative, and absolute spectral measures and for males and females. The overall findings contradict the common wisdom that EEG and alpha slow with age and that age related EEG change is on a continuum with findings in Alzheimer's disease where increased slowing predominates. PMID- 8450937 TI - 31P magnetic resonance spectroscopy in Alzheimer's and Pick's disease. AB - Previous studies have suggested a defect in phosphorus metabolism in Alzheimer's disease (AD) gray matter. We have studied phosphorus metabolites in both gray and white matter in autopsy specimens of nine subjects with late-stage AD, three with Pick's disease and seven age-matched controls. Phosphorus metabolites sugar phosphate (SU), phosphomonoester (PME), phosphodiester (PD), and inorganic phosphate (PI) were quantified as mole percentages in regional neocortical specimens using nuclear magnetic resonance spectroscopy. Senile plaque (SP) and neurofibrillary tangle (NFT) counts were determined in adjacent cortical sections. In the inferior parietal lobule gray and white matter, mole percentage normalized PME, and PD were significantly greater than control values in both AD and Pick's disease. A significant correlation was found between PD and NFT in AD parietal gray matter. Our data indicates that phosphorus metabolite alterations are present in two cortical degenerative diseases and are not likely to be specific for AD. PMID- 8450938 TI - Methanesulfonyl fluoride (MSF) blocks scopolamine-induced amnesia in rats. AB - Cholinesterase inhibitors, such as physostigmine and tetrahydroaminoacridine, have been found to alleviate some of the memory deficits characteristic of senile dementia of the Alzheimer's type (SDAT). Many toxic side effects, however, have been associated with the use of these compounds. Recently, a cholinesterase inhibitor, methanesulfonyl fluoride (MSF), was discovered to have low toxicity, central nervous system (CNS) selectivity, and a long therapeutic duration. The purpose of this research was to determine if MSF (1.5 mg/kg) would be effective in reducing or blocking amnesia induced by various doses of scopolamine (0.2, 0.6, and 2.0 mg/kg). One hundred and twenty-two female Sprague-Dawley albino rats were trained and retention tested in a Y-maze brightness discrimination task. MSF was highly effective in reducing scopolamine-induced amnesia. PMID- 8450939 TI - No aging effect on hippocampal type II glucocorticoid receptors in two inbred mouse strains. AB - We report here on the type II glucocorticoid receptor concentration in the hippocampal cytosol of two inbred strains of mice, C57BL/6J and DBA/2J, aged 2 and 24 months. Glucocorticoid receptors are usually considered as mediating cytotoxic effects of glucocorticoids on hippocampal neurons and modulating hippocampus-dependent behaviors. Either a decrease in glucocorticoid receptors with aging or no effect of aging have been reported previously. In order to test whether strain differences may explain these conflicting results, we have measured, using [3H]RU 28362, the hippocampal glucocorticoid receptor concentrations in two inbred strains of mice showing differential modifications of some hippocampus-dependent behaviors with aging. Our results show that there is neither a strain nor an age effect. PMID- 8450940 TI - Septohippocampal cholinergic changes after destruction of the A10-septal dopaminergic pathways. AB - Mice were injected bilaterally into the septum with 6-hydroxydopamine and 6 weeks later the hippocampi were assayed for activity of choline acetyltransferase, muscarinic receptor binding capabilities and for formation of inositol phosphate in response to direct (carbachol) or presynaptically elicited (K+) stimulation of the postsynaptic receptors. Levels of dopamine in the septum were reduced by 70% in the lesioned animals and hippocampal choline acetyltransferase was elevated by the same amount. The Bmax of muscarinic binding was significantly reduced without changes in Kd; nevertheless, carbachol-induced stimulation of formation of inositol phosphate was unaffected. The response to K+ was markedly elevated in the 6-hydroxydopamine-treated animals. Thus, the regulatory effect of A10-septal dopaminergic pathways on the septohippocampal cholinergic innervations is both on the presynaptic and postsynaptic levels. PMID- 8450941 TI - Effects of subchronic administration of pyritinol on receptor deficits and phosphatidylinositol metabolism in the brain of the aged mouse. AB - The effect of pyritinol, a commonly used nootropic drug, on receptor properties and function was investigated in different neuronal systems, possibly associated with age-related decline in brain function. Chronic treatment (15 days) of aged (22 months) female NMRI mice with pyritinol (200 mg/kg) restored the reduced density of N-methyl-D-aspartate receptors in the aged mouse brain. Furthermore, the total number of binding sites of the alpha 2-receptor ([3H]yohimbine binding) decreased after treatment with drug, while the number of high-affinity agonist binding sites ([3H]UK 14304 binding) was not changed. In both systems, receptor affinity was not influenced. The densities of other receptors investigated (muscarinic-cholinergic, benzodiazepine and beta-adrenergic) were not altered by treatment with pyritinol. Additionally, the effect of pyritinol on phosphatidylinositol (PI) metabolism was investigated in dissociated neurones from young and aged mice. Muscarinic-cholinergic induced accumulation of phosphatidylinositol and the inositol phosphate response due to activation of G protein by fluoride was increased in aged animals, treated with drug. The inositolphosphate response after stimulation with pilocarpine was slightly but not significantly increased. The metabolism of phosphatidylinositol in young animals was not altered by treatment with drug. These results support the hypothesis of a nootropic-mediated restoration of age-related brain deficits. Changes caused by pyritinol may be due to beneficial effects on age-related alterations of the properties of the neuronal membrane. PMID- 8450942 TI - Omega-conotoxin GVIA inhibits release of noradrenaline from rat hippocampal slices in the absence of extracellular calcium. AB - Slices of hippocampus of the rat, preincubated with [3H]noradrenaline ([3H]NA), were used to investigated the effects of omega-conotoxin GVIA (omega-CTX) on the release of [3H]NA evoked by 3,4-diaminopyridine (3,4-DAP, 200 microM), veratridine (0.7 microM) or monensin (0.01 microM) in the absence of extracellular CA2+. The 3H outflow, evoked by 3,4-DAP or veratridine, was inhibited by tetrodotoxin (TTX) or omega-CTX but the 3H outflow evoked by monensin was neither affected by TTX nor by omega-CTX in Ca(2+)-free medium, containing 1 mM EGTA. The release response to 3,4-DAP or veratridine was also blocked by omega-CTX in a concentration-dependent manner in Ca(2+)-free medium, containing 2.5 mM Mg2+ and the blockade was still complete after washing for 20 min with omega-CTX-free medium. The findings suggest that, under these conditions, the toxin might also block sodium channels. PMID- 8450943 TI - Antagonism of central pressor response to angiotensin II by alpha-human atrial natriuretic polypeptide at the preoptic area and posterior hypothalamus in rats. AB - Effects of alpha-human atrial natriuretic polypeptides (alpha-hANP) on pressor responses to angiotensin II (AII) were assessed at the preoptic area, posterior hypothalamus and central amygdaloid nucleus (ACE) in spontaneously hypertensive (SHR) and control normotensive Wistar-Kyoto (WKY) rats. Angiotensin II, administered intracerebroventricularly, at a dose of 100 ng produced a marked pressor response in hypertensive, as well as in normotensive rats and the response was potentiated in hypertensive rats. The response was antagonized in a dose-dependent manner by administration of alpha-hANP into the preoptic area and posterior hypothalamus but not to the amygdaloid nucleus. The antagonism was more marked in hypertensive than in normotensive rats. Angiotensin II, when injected directly to the preoptic area at a small dose of 10 ng similarly evoked a marked pressor response, which was augmented in hypertensive rats. This response was also antagonized by coadministration of alpha-hANP to the preoptic area in hypertensive but not in normotensive rats. The results suggest that the antagonistic relationship between ANP and AII exists at the preoptic area and posterior hypothalamus, probably implying that the activity of the ANP and AII systems in brain play a role in centrally controlling the cardiovascular system and is altered at these areas in genetically hypertensive rats. PMID- 8450944 TI - The effect of cocaine on membrane potential, on membrane depolarization by veratridine or elevated [K]o and on sodium/potassium permeability ratios in synaptosomes from the limbic cortex of the rat. AB - Effects of cocaine on the synaptosomal membrane potential (Em), on membrane depolarization induced by veratridine or elevated [K]o and on sodium/potassium permeability ratios (pNa/pK), have been measured in buffer containing either low or high [Na]. Fluorescence of the dye rhodamine 6G was used to measure the membrane potential. Cocaine began to reduce the Em (depolarized) at concentrations between 10(-6) and 10(-5) M in low [Na] buffer and between 10(-5) and 10(-4) M in high [Na] buffer. Maximum depolarization (with 10(-3) M cocaine) was 21 mV in low [Na] buffer and 11 mV in high [Na] buffer. Cocaine also reduced the depolarization caused by veratridine or elevated [K]o; the effective concentration of cocaine in reducing the response to veratridine was one-tenth that necessary to reduce the response to elevated [K]o. The antagonism by cocaine of the response to veratridine was similar to that found by other investigators; however, this action would tend to oppose depolarization and thus cannot explain the depolarizing effect of cocaine alone. The antagonism by cocaine of the depolarization caused by elevated [K] was consistent with a reduction in pK; such a change in pK could explain the observed reduction in Em caused by cocaine alone. The effect of cocaine (10(-3) M) on the Em was also measured as a function of [K]o at low and high [Na]o. Cocaine caused membrane depolarization at all [K]o's (3.9-19.2 mV), an effect that was somewhat greater in the low [Na] medium. These measurements of Em were fitted to the Goldman equation and the ratio of pNa/pK estimated. The presence of cocaine increased the estimate of pNa/pK by 45.7%, presumably by reducing pK. PMID- 8450945 TI - Non-uniform propagation of epileptiform discharge in brain slices of rat neocortex. AB - In neocortical brain slices of the rat that were exposed to 50 microM picrotoxin, low-intensity stimuli evoked all-or-none epileptiform events that propagated across the slice with an average velocity of 0.07 m/s. Simultaneous recordings from pairs of electrodes, in which one was held in a constant position and the other was systematically advanced across the slice in small steps, revealed that propagation of the synchronous activity was saltatory rather than uniform. Analysis of the propagation pattern showed that local regions (< 1000 microns) of uniform velocity were separated by distinct borders. Within these regions, local propagation velocity was determined by the threshold for synchronous activation of still-smaller (< 200 microns) neuronal aggregates. Although the velocity was sensitive to physiological factors that affect the precise threshold for synchronization, the location of the borderlines between adjacent regions remained unchanged. We propose that these invariant borders reflect the details of local neuronal organization within the slice, and that the pattern of propagation of epileptiform discharge is a manifestation of the intrinsic organization of the neocortex when deprived of afferent input. PMID- 8450946 TI - Examination of the effects of cholecystokinin 26-33 and neuropeptide Y on responses of visual cortical neurons of the cat. AB - Extracellular recordings were made from 160 neurons in area 17 (n = 120) and area 18 (n = 40) of the visual cortex of anesthetized cats. Cells were classified according to their receptive field properties and their intracortical positions were evaluated histologically. Cholecystokinin 26-33, antagonists, (cholecystokinin 27-32, cholecystokinin 27-33 and proglumide), amino acids, neuropeptide Y and solvent vehicle (control), were administered to cells by microiontophoresis (cholecystokinin and neuropeptide Y) or by pressure (neuropeptide Y). The results of the tests with cholecystokinin 26-33 fell into four categories: enhancement (31%), suppression (24%), mixed, i.e. either biphasic responses or dose-related alterations in the direction of effect (20%), and no effect (25%). Enhancements of the visually elicited response were more prevalent in simple (43%) and unimodal/movement-sensitive (34%) cells than in complex (7%) cells. The converse was true for suppressions: 19% of simple cells, 24% of unimodal/movement-sensitive cells, and 31% of complex cells were suppressed. Thirty per cent of the unaffected cells were complex or unimodal/movement-sensitive; only 14% were simple. Cells in layers II-IV were more likely to have firing enhanced than suppressed by cholecystokinin 26-33. The converse was true for cells in layers V and VI, where 50% of responses were suppressed and only 22% were enhanced. Unaffected cells were found predominantly in layer III of areas 17, and the lower part of layer III and layer IV of area 18. Cholecystokinin 26-33 sometimes exerted delayed, response-suppressant effects; it also occasionally elevated responsiveness preferentially within the upper ranges (10-20 degrees/s) of velocity tuning curves. Cholecystokinin 26-33 altered the response-suppressant action of GABA in 11 of 19 visually sensitive cells. The peptide potentiated the visual responsiveness in half of the cells where cholecystokinin 26-33 diminished the GABA-induced suppressions (n = 8). The presumed antagonists either exerted no effect on firing or on cholecystokinin 26 33-induced effects, or had cholecystokinin 26-33-like actions themselves. There was a reversible partial antagonism of the effects of cholecystokinin 26-33 on only two of 11 cells tested. Neuropeptide Y injected by pressure or administered iontophoretically had variable and inconsistent effects on the visually evoked responses of 29 additional neurons from those described above. These effects were indistinguishable from those of the vehicle whether spontaneous activity, magnitude of the visually elicited response, spatial integrity of the RF substructure, orientation or velocity tuning was assessed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8450947 TI - Localization of GABA-like immunoreactivity in the monkey amygdala. AB - Neurons exhibiting GABA-like immunoreactivity were identified in the monkey amygdala using an avidin-biotin immunohistochemical technique. The pattern of GABA immunoreactivity was very similar in the basolateral and superficial amygdaloid nuclei. In these regions GABA-positive cells were nonpyramidal neurons that were often arranged in clusters or curvilinear rows. These GABA-positive nonpyramidal neurons constituted about 25% of the total neuronal population of the basolateral and superficial amygdaloid nuclei. Numerous GABA-positive puncta resembling axon terminals were observed both in the neuropil and encapsulating the perikarya of GABA-negative pyramidal cells. The pattern of GABA-like immunoreactivity was different in the central and medial amygdaloid nuclei. These regions contained a very dense array of GABA-positive puncta. There were numerous GABA-positive neurons in the lateral subdivision of the central nucleus and fewer cells in the medial nucleus and medial subdivision of the central nucleus. Many immunoreactive puncta were observed contacting the perikarya and dendrites of GABA-positive cells in these regions. The intercalated nuclei consisted of numerous, small, GABA-positive neurons and a few, larger, GABA-negative cells. Both cell types were contacted by GABA-positive puncta. This study indicates that neuronal subpopulations in each of the amygdaloid nuclei of the monkey are GABAergic. The pattern of immunoreactivity varies in different amygdaloid regions and is very similar to that described in the rat. Certain aspects of the functional organization of this rich GABAergic circuitry can be elucidated by correlating the findings of the present investigation with previous anatomical, physiological, and pharmacological studies of the amygdala. PMID- 8450949 TI - Mechanisms of supraspinal correction of locomotor activity generator. AB - In experiments on immobilized decerebrate cats, data about reorganization of efferent activity parameters of the forelimb and hindlimb locomotor generators evoked by electrical stimulation of descending systems were obtained. The generators controlling both forelimb and hindlimb locomotor movements were found to be characterized by the existence of stable states at which total influence of different descending systems on these generators was extremely limited. These data enable us to conclude that the sense of activity reorganization in locomotor generators of both forelimb and hindlimb under the influence of descending system signals is in bringing the motor program to a dynamic relation with supraspinal inflow, where a sufficient degree of limitation and balancing of the influences of corresponding descending systems on the interneuronal nets, determining time and phase characteristics of these generators, is ensured. Possible mechanisms of realization of this interaction between descending signals and locomotor activity generators are discussed. PMID- 8450948 TI - Serotonergic, cholinergic and nociceptive inhibition or excitation of raphe magnus neurons in barbiturate-anesthetized rats. AB - Neurons in the nucleus raphe magnus were recorded extracellularly from barbiturate-anesthetized rats, and were classified by their responses to noxious mechanical stimulation as either pinch-excited, pinch-inhibited or biphasic (inhibited then excited). They were then subjected to iontophoresis of serotonin, some serotonergic agonists and antagonists, acetylcholine, and gamma-amino-n butyric acid. Serotonin reduced the spontaneous firing of most pinch-inhibited cells (79%). Significantly fewer (P < 0.05) pinch-excited and biphasic cells were inhibited by serotonin (40% and 45%, respectively); in these two cell classes, the observed response was often excitation (30% and 14%), or inhibition for 10 30s followed by excitation for the next 1-2 min (25% and 36%). Acetylcholine showed a similar, statistically significant distribution of effects (P < 0.05), inhibiting all pinch-inhibited neurons (n = 10) but fewer pinch-excited (53%, n = 17) and biphasic neurons (20%, n = 10). Excitation, or excitation then inhibition, was again found frequently among the remaining pinch-excited and biphasic cells. The effect of gamma-amino-n-butyric acid was only inhibitory. In all three nociceptive classes, the serotonin-1A agonist buspirone (n = 15) was inhibitory (87%) and the serotonin-1C/2 antagonist ketanserin (n = 20) was excitatory (35%). The mixed serotonin-1/2 antagonist methysergide (n = 10) was inhibitory (50%) or excitatory (40%). 8-Hydroxy-dipropylaminotetralin (n = 3) was found to increase spontaneous activity (possibly because of partial serotonin-1A agonsim), and +/- propranolol (n = 4) to reduce it (possibly through beta adrenoceptor antagonism, not serotonin-1A antagonism).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450950 TI - Grafting in acute spinal cord injury: morphological and immunological aspects of transplanted adult rat enteric ganglia. AB - We have studied allogeneic transplants of adult rat enteric ganglia in order to evaluate their use as donor tissue for eventual autografts in rodent spinal cord injury models. Female Sprague-Dawley rats of similar weights served either as transplant donors or as recipients. A glass micropipette of 0.8 mm diameter was used to create a local penetrating injury of the lower thoracic spinal cord and the transplant material was pressure injected through the pipette within the neural parenchyma. Ganglia of the myenteric plexus adhering to the stratum longitudinal muscularis were dissected from portions of the jejunum and ileum. Following partial enzymatic digestion and mechanical disruption of the myenteric plexus and muscle tissue (labeled with adherent rhodamine conjugated microbeads), reaggregates of myenteric plexus and muscle were suspended in growth medium and cultured in vitro for one to two days prior to transplantation. Transplants were examined at three, four, six, and eight weeks after surgery. Some of the donor tissue was grown in vitro, in order to determine its cellular composition. These cultured explants were fixed after 10 days, and like myenteric plexus and muscle grafts, were stained histochemically for acetylcholinesterase and observed by fluorescence and light microscopy. At the earlier post-transplantation periods, grafts contained several clusters of enteric ganglion cells that were positive for acetylcholinesterase and exhibited ultrastructural features characteristic of the enteric nervous system. They had well-defined boundaries. Reactive astrocytes and their processes remained located within the host spinal cord adjacent to the boundary region of the grafts. Likewise, macrophages were located in areas abutting the graft. Newly formed vasculature penetrated the graft interior and appeared to be continuous with the host vessels. Grafts grown for at least eight weeks were characterized by interdigitating boundaries. Finger-like protrusions of graft tissue containing fibroblasts and collagen intermixed with adjacent gray and white matter of the host cord. Such transplants also had reactive astrocytes and ED1-positive macrophages. At this later stage, several groups of ganglion cells were identified that were intensely acetylcholinesterase-positive; however, only two of four grafts were recovered, whereas two of the transplants degenerated. We postulate that degeneration of allogeneic grafts may occur as a result of ongoing immune responses of the host which could be prevented by use of autogeneic enteric ganglia. Our studies show that fully differentiated enteric ganglia can survive transplantation to acutely injured spinal cord of adult rats. PMID- 8450951 TI - Cytoskeleton-mediated, age-dependent lateral topography of lectin-gold-labelled molecules on the plasma membrane of cultured neurons: a statistical view. AB - In dissociated spinal cord neurons (12-day-old mouse embryo, monolayer culture), an electron microscopic study was carried out to examine quantitatively the rearrangement of wheat-germ agglutinin-gold-labelled molecules on the neuronal somatic surface at two developmental stages (on the fifth and 15th days in vitro), and after cytoskeletal interruptions. In tests, before labelling the cultures were incubated with colchicine or cytochalasin in order to affect microtubules or mostly actin filaments, respectively. Samples of electron micrographs that display soma membrane (profile) fragments were quantified. A set of stochastic geometry approaches was accomplished, which allowed statistical and stereological analysis of labelling. Images that illustrate the lateral (surface) patterns of label were simulated. On the fifth day in vitro, both colchicine and cytochalasin were found to cause an increase in the surface density and aggregation of wheat-germ agglutinin label relative to controls, the effect of cytochalasin being significantly more profound. By the 15th day in vitro, treatment with both drugs led to a similar tendency towards heavy aggregation of wheat-germ agglutinin labels. In contrast, neuron processes showed an opposite tendency of label rearrangement, which suggests lateral migration of labelled molecules, as a result of drug action. Possible molecular mechanisms involved in the phenomena are discussed. PMID- 8450952 TI - Reorganization of brain spectrin (fodrin) during differentiation of PC12 cells. AB - Fodrin has been shown to redistribute dynamically between cytoplasmic and plasma membrane-associated compartments upon the differentiation of T lymphocytes. We studied the changes of distribution of fodrin in PC12 cells upon neuronal differentiation induced by nerve growth factor. To visualize preferentially the elements that were tightly associated with cytoskeletal structures, we performed immunofluorescence and immunoelectron microscopy on saponin-extracted cells. In undifferentiated PC12 cells, fodrin was distributed mostly underneath the plasma membrane. However, after the administration of nerve growth factor, perinuclear spot-like aggregates of fodrin appeared. Double-labeling immunofluorescence revealed that the cytoplasmic fodrin spot was co-localized with the intermediate filament proteins, peripherin and neurofilament. Immunogold electron microscopy showed that fodrin and neurofilament were localized in close association in the perinuclear regions enriched with intermediate filaments. With prolonged exposure to nerve growth factor, fodrin and intermediate filaments spread to the cytoplasm and neurites. These results suggest that there is a dynamic reorganization of fodrin during differentiation of PC12 cells, and that fodrin is first recruited in the perinuclear region closely associated with intermediate filaments. This dynamic reorganization of fodrin may represent important, previously unrecognized aspects of the morphological differentiation of neurons. PMID- 8450953 TI - Visual input and lateralization of brain function in learning in the chick. AB - Several lines of evidence (biochemical, neuroanatomical, electrophysiological, and behavioural) have indicated a critical role for the intermediate medial hyperstriatum ventrale of the chick forebrain in the acquisition of a passive avoidance response. Previous lesion studies indicated that bilateral or left, but not right, pretraining intermediate medial hyperstriatum ventrale lesions interfere with the acquisition of this task. We have further analysed this asymmetrical involvement of the intermediate medial hyperstriatum ventrale by use of a monocular learning protocol and intermediate medial hyperstriatum ventrale lesions (sham, bilateral, or unilateral). The results indicated that there is interocular transfer of information of passive avoidance learning between the two eye systems, with a tendency to be more successful from the right eye system to the left than in the opposite direction. As in binocular conditions, bilateral pretraining intermediate medial hyperstriatum ventrale lesions impair learning in monocularly trained animals. Unilateral lesions to either left or right monocularly trained experimental animals resulted in amnesia when they were made to the right intermediate medial hyperstriatum ventrale and the chicks were trained/tested with the left eye open. These results indicate that, although right intermediate medial hyperstriatum ventrale lesions do not result in amnesia in binocular animals, this region is capable of participating in memory acquisition processes. They also suggest a connection between lateralization of intermediate medial hyperstriatum ventrale function in passive avoidance learning and the behavioural and structural visual asymmetries known to occur in chicks. PMID- 8450954 TI - Different subsets of displaced ganglion cells in the pigeon retina exhibit cholecystokinin-like and enkephalin-like immunoreactivities. AB - Immunohistochemical and retrograde tracing techniques were combined in order to identify chemically specific displaced ganglion cells in the pigeon retina. About 15% of the displaced ganglion cells that were retrogradely labeled following injections of different tracers into the accessory optic nucleus were shown to contain cholecystokinin8-like immunoreactivity. These cells were medium to large (15-30 microns) and located mostly in the peripheral retina. Another population of about 9% of the retrogradely labeled displaced ganglion cells was shown to contain leucine-enkephalin-like immunoreactivity. These cells were medium-sized (11-18 microns) and distributed almost evenly throughout the retina. These two types of displaced ganglion cells represent together only about 0.1% of the total number of ganglion cells in the pigeon retina. Taken together with previous results, these data indicate that the displaced ganglion cells of the avian retina may comprise several chemically specific cell types. The present results also contribute information on the chemical heterogeneity of retinal ganglion cells. PMID- 8450955 TI - Attenuation of microtubule-associated protein 1B expression by antisense oligodeoxynucleotides inhibits initiation of neurite outgrowth. AB - Microtubule-associated protein 1B, formerly also known as microtubule-associated protein 5, is the first structural microtubule accessory protein to appear in outgrowing axons. In PC12 pheochromocytoma cells microtubule-associated protein 1B levels increase several-fold after the addition of nerve growth factor and this increase is correlated with the initiation of process formation. To determine whether microtubule-associated protein 1B is essential for neurite outgrowth, we used antisense oligodeoxynucleotides to inhibit its expression in nerve growth factor-treated PC12 cells in the rat. The application of several different antisense oligodeoxynucleotides to the microtubule-associated protein 1B mRNA sequence inhibited both microtubule-associated protein 1B expression and neurite extension. Specificity was shown by the lack of effect of control sense oligonucleotides and by the lack of effect of the microtubule-associated protein 1B antisense oligodeoxynucleotides on the expression of either tubulin or microtubule-associated protein 3, another microtubule-associated protein whose synthesis is stimulated by nerve growth factor treatment of PC12 cells. After removal of the antisense oligodeoxynucleotides, microtubule-associated protein 1B expression recovered to normal levels and the cells grew normal neurites with the timing and morphological characteristics of normal nerve growth factor-induced outgrowth, indicating that the blockade was not because of non-specific toxic effects. These results indicate that microtubule-associated protein 1B is an essential component of the molecular mechanism underlying the formation of neuronal processes. PMID- 8450956 TI - The supraoptic nucleus of the adult rat hypothalamus displays marked sexual dimorphism which is dependent on body weight. AB - The neurons of the supraoptic nucleus in the rat hypothalamus are reported not to possess receptors for gonadal steroids and sexual dimorphism has not previously been described in this nucleus. We have analysed this nucleus in groups of Sprague-Dawley rats (six males or six females per group), one, two, six, 12 and 18 months after birth. Body and brain weights were recorded, the volume of the nucleus was determined from the right hemisphere and all other quantitative parameters were determined from the left nucleus. In addition, different groups of four male and four female rats aged two and 18 months were analysed after immunocytochemical staining to distinguish between vasopressin and oxytocin neurons. The total number of neurons was constant in all groups studied, despite which the volume of the supraoptic nucleus increased progressively with age in both males and females. The cross-sectional areas and volumes of supraoptic neurons also increased with age. The volume density of the neuropil remained constant in all groups and there was a progressive decrease with age in the numerical density of neurons. Immunocytochemistry revealed that the age-dependent increases in the size of the neurons involved primarily the vasopressin neurons. The age-related changes were much greater in males than in females, resulting in significant differences between the sexes at two, six, 12 and 18 months with respect to the volume of the supraoptic nucleus, the cross-sectional areas of neuronal somata and nuclei, and the volume of supraoptic neurons. Thus the supraoptic nucleus and its vasopressin neurons are larger in adult males than in age-matched females. Since we have also shown that body weight is very closely correlated with changes in the size of supraoptic neurons, and adult male rats are heavier than females of the same age, we suggest that these size changes reflect adaptation of the vasopressin neurons of the supraoptic nucleus to increasing functional demands associated with the regulation of water balance in bodies of increasing size. PMID- 8450957 TI - The differential expression patterns of messenger RNAs encoding non-N-methyl-D aspartate glutamate receptor subunits (GluR1-4) in the rat brain. AB - The messenger RNA expression of non-N-methyl-D-aspartate glutamate receptor subunits (GluR1-4), considered alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid type, was investigated in rat brain by in situ hybridization histochemistry using oligonucleotide probes specific to each subunit sequence. GluR1-4 subunit messenger RNAs were expressed widely and abundantly throughout the CNS. However, the combination of expression pattern varied notably according to location. GluR2 messenger RNA was expressed most strongly and widely, with most areas except the Bergmann glia containing this messenger RNA. GluR4 messenger RNA was also present widely, although the expression level was low. However, we observed many areas which lacked or expressed very little GluR1 messenger RNA, such as some nuclei in the general motor system and auditory system. In addition, some nuclei in the hypothalamus and general somatosensory system lacked or expressed very little GluR3 messenger RNA. These results suggest that in the rat CNS non-N-methyl-D-aspartate receptors varied their composition according to the area where they were expressed, and that the combination pattern might be related to the functional role of neurons. PMID- 8450958 TI - Effect of temperature on synaptic function after reduced oxygen and glucose in hippocampal slices. AB - We performed experiments in vitro to observe electrophysiological events that may relate to the protective effect of decreased temperature during cerebral ischemia in vivo. Extracellular field potentials were recorded from area CA1 of rat hippocampal slices with reduced oxygen and 2.0 mM D-glucose, producing irreversible changes within c. 10 min (more slowly than with complete deprivation of oxygen and glucose but more rapidly than with hypoxia alone). At 36 degrees C, synaptic potentials rapidly disappeared, followed by a d.c. negative shift similar to spreading depression. Elevated oxygen and glucose were reapplied within 5 min of each negative shift (duration of hypoxia ranged from 15 to 21 min). Application of normal medium for up to 45 min after negative shifts did not allow synaptic potentials to recover. At 33 degrees C negative shifts from reduced oxygen were delayed and excitatory postsynaptic potentials recovered in one experiment. At 31 degrees C negative shifts were usually absent and synaptic potentials always recovered, even with > 50 min of reduced oxygen and glucose. At both 33 degrees C and 31 degrees C, excitatory postsynaptic potential amplitude oscillated one or more times, whether or not a negative shift occurred. Our results show that negative shifts and irreversible loss of synaptic activity from hypoxia in vitro are delayed or prevented by decreased temperature. PMID- 8450959 TI - Cholinergic regulation of hippocampal brain-derived neurotrophic factor mRNA expression: evidence from lesion and chronic cholinergic drug treatment studies. AB - Quantitative in situ hybridization and northern blot analysis techniques were used to determine the effects of removal of the cholinergic input on levels and topographical distribution of brain-derived neurotrophic factor mRNA in the hippocampus of adult rats. First, the effects of partial and full fimbrial transections, which result in partial and near-total cholinergic deafferentation respectively, were compared. Twenty-one days after partial unilateral fimbrial transections, there were significant decreases in brain-derived neurotrophic factor mRNA expression throughout the hippocampal formation. Decreased expression of brain-derived neurotrophic factor mRNA was evident in all areas of localization within the hippocampal formation. The decreases amounted to 22-36% reductions compared with unlesioned control animals. Brain-derived neurotrophic factor mRNA levels were decreased to a greater extent (50-69%) following full unilateral fimbrial transections. Quantitative northern blot analysis indicated that hippocampal BDNF mRNA was decreased by 29 and 68%, three weeks after partial or full unilateral fimbrial transections, respectively. The extent of the reductions in brain-derived neurotrophic factor mRNA levels correlated with reductions in acetylcholinesterase staining density and cholinergic terminal density determined by quantitative autoradiographic analysis of [3H]vesamicol binding sites. Second, we found that chronic treatment with atropine (20 mg/kg per day for 14 days) decreased (by 54%) brain-derived neurotrophic factor mRNA levels in all areas of localization within the hippocampus. In contrast, chronic treatment with nicotine (1.18 mg/kg per day for 14 days), a treatment known to desensitize nicotinic receptors, did not affect brain-derived neurotrophic factor mRNA expression in the hippocampal formation. The findings provide evidence for cholinergic muscarinic regulation of brain-derived neurotrophic factor mRNA expression in the adult rat hippocampal formation and they suggest the existence of a tonic stimulation of brain-derived neurotrophic factor synthesis by the cholinergic afferents. PMID- 8450960 TI - Lesion-induced expression of low-affinity nerve growth factor receptor immunoreactive protein in Purkinje cells of the adult rat. AB - Normal adult cerebellar Purkinje cells in the rat rarely express low-affinity nerve growth factor receptor immunoreactivity. However, intense anti-low-affinity nerve growth factor receptor immunostaining was observed as early as one day after a lesion of the cerebellar cortex. Low-affinity nerve growth factor receptor immunoreactivity was confined to a selected group of Purkinje cells, the number of which reached a maximum at three days postlesion, and, in some neurons, persisted up to 10 days after damage. The intensity of Purkinje cell immunolabeling decayed abruptly with distance from the lesion site. Reactive Purkinje cells exhibited deposition of immunoreaction product in the cell soma, dendrites and axons. Characteristically, most Purkinje cell axons exhibiting intense low-affinity nerve growth factor receptor immunoreactivity had beaded, varicose morphology. Varicose fibres with the appearance of recurrent collaterals of Purkinje cell axons were also low-affinity nerve growth factor receptor positive. Our results indicate that adult rat Purkinje cells increase low affinity nerve growth factor receptor-immunoreactive protein in response to injury, suggesting that, in the cerebellum, low-affinity nerve growth factor receptor or low-affinity nerve growth factor receptor-like molecules may be involved in regulating neuronal plasticity during adulthood. PMID- 8450961 TI - Stimulus-bound perseveration after frontal ablations in marmosets. AB - Marmosets with bilateral ablations of either the lateral or ventral surface of the frontal lobes were found to perseverate on object but not spatial serial reversal. They also perseverated on reversal of a visuospatial task where different stimuli required different spatial responses. No differences were found between the two lesion groups. Since the control animals showed mild perseveration on spatial but not object serial reversal it is argued that frontal ablations do not lead to perseveration of a natural tendency but rather that object and visuospatial perseveration are forms of stimulus-bound behaviour which do not occur when the animal is performing a spatial task in which stimulus position is irrelevant. Perseveration was reduced by pretreatment with a dopamine blocking drug (haloperidol). It is suggested that information from temporal lobe mechanisms, involved in long-term memory, and from frontal lobe mechanisms, which exert shorter acting influences on behaviour, compete within the basal ganglia to determine stimulus choice. The ascending dopaminergic pathway may modulate the balance between these competing factors. PMID- 8450962 TI - Effects of medial dorsal thalamic and ventral pallidal lesions on the acquisition of a conditioned place preference: further evidence for the involvement of the ventral striatopallidal system in reward-related processes. AB - In our previous work, it has been established that the basolateral amygdala and ventral striatum are part of a neural system that is involved in reward-related processes. However, it is unclear how information processed in this limbic-motor interface may come to affect incentive motivational responses. The present experiments have investigated the involvement of post-striatal elements of the ventral striatopallidal system in the rat. Lesions of the anterior or posterior domains of the ventral pallidum, which receives the major outflow from the ventral striatum, or the nucleus medialis dorsalis of the thalamus, which receives projections from both the ventral pallidum and also the basolateral amygdala, were made by infusing the excitotoxin, ibotenic acid. The effects of the lesions on the acquisition of a place preference conditioned by exposure of hungry rats to sucrose were then measured. Lesions of either the anterior or posterior ventral pallidum significantly attenuated, whereas lesions of the medial dorsal thalamus completely abolished, the acquisition of a conditioned place preference, provided that the latter lesions included the medial-lateral extent of the nucleus. Medial dorsal thalamic lesions did not damage the stria medullaris or medial habenula. Ingestion of sucrose following 23 h deprivation was unaffected by either ventral pallidal or medial dorsal thalamus lesions and thus disruption of place preference acquisition was not secondary to changes in primary motivation. The results indicate that reward-related processes, as measured in the place preference conditioning paradigm, may depend upon ventral striatopallidal outflow that engages medial dorsal thalamus-frontal cortex mechanisms, in addition to the previously highlighted direct outflow to brainstem elements of the motor system. PMID- 8450963 TI - Rat amygdaloid neuron responses during auditory discrimination. AB - To investigate amygdaloid contribution to stimulus-affect association and to emotional behavior, single neuron activity was recorded in the basolateral and corticomedial amygdala of the rat amygdala during discrimination of conditioned cue tones associated with positive (glucose and intracranial self-stimulation) and negative (weak electric footshock) unconditioned stimuli. Amygdaloid neurons that responded to two rewarding unconditioned stimuli responded in the same manner to both. Responses to conditioned cue tones and those to rewards were also significantly related, suggesting that amygdaloid neuronal responses to conditioned stimuli are closely related to the affective nature of the corresponding unconditioned stimulation. These might be neuronal functions that underlie stimulus-affect association in the amygdala. In random repeated trials, including acquisition to conditioned cue tones and extinction after acquisition, response plasticity was more evident in basolateral than in corticomedial neurons. Furthermore, more basolateral than corticomedial neurons differentiated glucose and its cue from intracranial self-stimulation and its cue by responding to one but not the other. More basolateral than corticomedial neurons were excited by intracranial self-stimulation and its cue and inhibited by footshock and its cue. The differences between the two nuclear groups suggest that basolateral neurons are more plastic and discriminative, and corticomedial neurons respond indiscriminately to positive and negative unconditioned or conditioned stimuli. The results indicate amygdaloid neuron involvement in stimulus-affect association. Basolateral neurons may be more involved than corticomedial neurons in discriminating and learning conditioned stimuli. PMID- 8450964 TI - Reversal of paw preference after ablation of the preferred forelimb primary motor cortex representation of the rat depends on the size of the forelimb representation. AB - Animals were tested for forelimb preference in a grasp or in a force task before microstimulation mapping of the primary motor cortex contralateral to the preferred forelimb. The size and location of the preferred forelimb primary motor cortex representation was determined and ablated. Seven days later, forelimb preference was again evaluated. Reversal of the initial preference after cortical ablation depended on the size of the preferred forelimb primary motor cortex representation. The mean size of the forelimb representation of the animals that immediately reversed forelimb preference after the cortical ablation was significantly smaller than the mean size of the representation of the animals that did not reverse forelimb preference in three consecutive tests seven days after the lesion. In another experiment, the size, location, and threshold currents of the forelimb representations were evaluated bilaterally before the forelimb preference test. The mean size of the preferred representations did not differ from the mean size of the non-preferred representations. However, when the primary motor cortex representation of the preferred forelimb was ablated, reversal of the initial preference depended, as in the previous experiment, on the size of the forelimb representation. In conclusion, reversal of forelimb preference after ablation of the preferred forelimb primary motor cortex representation depends on the size of the forelimb representation. Moreover, forelimb preference in a behavioral task is not associated with a larger forelimb representation in the contralateral primary motor cortex. PMID- 8450965 TI - Immunohistochemical evidence for the absence of central neuron projection to pial blood vessels and dura mater. AB - The present work shows that, in rat pial vessels and dura mater, all the nerve fibres observable by confocal fluorescence microscopy belong to the peripheral nervous system. It has been postulated that central nervous structures such as the raphe nuclei and the locus coeruleus could send direct projections to meningeal blood vessels. Mature neurons, whose perikaryons and axons are entirely located within the central nervous system, express the low molecular mass neurofilament protein and not the 57,000 mol. wt intermediate filament protein called "peripherin". This is the case for both raphe nuclei and locus coeruleus neurons [Leonard et al. (1988) J. Cell Biol. 106, 181-193]. Neurons which send axons outside the central nervous system or ganglionic neurons of the peripheral nervous system systematically express both proteins [Portier et al. (1984) Devl Neurosci. 6, 335-344]. Double labelling of pial vessels and meningeal tissue with antibodies directed against low molecular mass neurofilament and peripherin revealed nerve fibres immunoreactive to both antibodies and no nerve fibres reactive only to the low molecular mass neurofilament antibody. Conversely, cortical nerve fibres were immunoreactive only to the low molecular mass neurofilament antibody. It is thus concluded that the raphe nuclei and the locus coeruleus do not directly innervate meningeal tissues and, therefore, that these nuclei cannot directly intervene in cerebrovascular pathologies such as migraine headache or vasospasm. Secondarily, the present work also allowed for the first time the accurate observation of the spatial organization of the complete cerebrovascular innervation. Three main types of nerves can be defined on a morphological basis. A high proportion of these nerve fibres, either isolated or grouped in bundles, are varicose nerve fibres. Contacts between adjacent varicosities of the same type, which have been occasionally observed by electron microscopy, appear to be a very frequent feature. PMID- 8450966 TI - Electron microscopic localization and expression on cultured cells of a novel surface-associated molecule in the rat central nervous system. AB - Subcellular localization and in vitro expression of a newly raised monoclonal antibody 374 antigen, which outlines a subset of neurons in various regions of the rat CNS, were studied. Electron microscopy revealed that the immunoreactivity is associated with the outer surfaces of neuronal subsets, the surfaces of glial cell processes facing such neurons and less frequently, with the Golgi apparatus and inner cell surfaces. The monoclonal antibody also stained part of the cytoplasm of a population of dendrites. In order to test whether the antigen originates from neurons, we examined the expression of the antigen in cultured cortical cells. Double immunofluorescence staining with neuron-specific enolase and glial fibrillary acidic protein revealed that the antigen is expressed on a subset of neuronal cells and to a lesser extent on glial cells. The antigen is considered to be expressed on the outer surface because the cells were stained by the monoclonal antibody irrespective of whether they were alive or fixed. The monoclonal antibody 374 antigen may be a novel neuronal surface molecule which plays a role in neuron-neuron or glial-neuron interactions in the CNS. PMID- 8450967 TI - An ultrastructural study of the binding of an alpha-D-galactose specific lectin from Griffonia simplicifolia to trigeminal ganglion neurons and the trigeminal nucleus caudalis in the rat. AB - The pattern of binding by the isolectin I-B4 from Griffonia simplicifolia to trigeminal ganglion neurons and the trigeminal nucleus caudalis has been investigated at the ultrastructural level in the rat. This lectin bound to small ganglion neurons with two different binding patterns. The majority of the ganglion cells labelled had reaction product throughout their cytoplasm and this was associated with the Golgi apparatus and endoplasmic reticulum. In a second group of small ganglion neurons the binding was only found on the surface plasma membrane of the cells. In the trigeminal tract the cytoplasm of many unmyelinated axons and a few small myelinated axons was found to bind this lectin. A very thin band of staining was also found on the inner and outer edges of the myelin sheaths of other myelinated axons. Staining of synapses was found throughout laminae I and II with the highest frequency in the inner part of laminae II. These synapses made both simple and complex connections with one or more dendrites, contained clear round vesicles and had asymmetric synaptic densities. Some of the glomerular synapses stained were observed to receive presynaptic synapses containing small clear flattened vesicles. Synapses containing both clear round and large dense core vesicles were unstained. Some staining was also found in dendrites. In weakly fixed tissue, staining was also found around some glial cells and on the luminal membranes of capillary endothelial cells. This lectin is a valuable tool for studies of the "non-peptide" group of C-fibre primary afferents. PMID- 8450968 TI - Microglia and the developing olfactory bulb. AB - The developmental appearance of microglia in the rat olfactory bulb was investigated through the use of selective staining with the B4-isolectin from Griffonia simplicifolia. No changes in the density or distribution of either the spherical, macrophage "ameboid" form or the highly arborized "ramified" variety of microglia were observed in the superficial layers of the bulb between postnatal days 10 and 30. The subependymal zone exhibited the only substantial population of ameboid cells and the only developmental increases in ramified cell density during this time-period. External single naris closure, which enhances cell death in the ipsilateral bulb, did not affect microglia density, presumably due to the unusually high numbers of microglia normally present in the bulb. The olfactory bulb has a dense and relatively uniform population of microglial cells from very early stages of postnatal life, perhaps because of the constant turnover of cells and processes. PMID- 8450969 TI - Interleukin-1 binding sites on astrocytes. AB - Interleukin-1 has been shown to have regulatory effects on glial cell functions. In this study, we examined the capacity of astroglial cells to specifically bind recombinant iodinated human interleukin-1 alpha. This was performed in mouse brain by both in situ and in vitro autoradiography, on areas of gliosis and on astrocytes and microglia primary and secondary cultures respectively. Specific binding was shown in the brain sections over areas of glial proliferation, and in addition, quantitative autoradiography was performed. Analysis of competition experiments by autoradiography led to EC50 values of 5 x 10(-11) M for human interleukin-1 alpha and approximately 10(-9) M for the interleukin-1 receptor antagonist. In cultures, iodinated human interleukin-1 alpha bound specifically to astrocytes but was unable to bind to microglial cells. Competition binding experiments in astrocyte cultures led to EC50 values of 8 x 10(-11) M and 1 x 10( 10) M for human interleukin-1 alpha and mouse interleukin-1 beta respectively, and an EC50 higher than 10(-9) M for the antagonist. The presence of interleukin 1 receptors on astroglial cells provides biochemical support for the various effects of interleukin-1 in the central nervous system, particularly those concerning the formation of scar tissue, possibly by astroglia proliferation after brain injury. PMID- 8450970 TI - Neurogenic and non-neurogenic mechanisms of plasma extravasation in the rat. AB - We describe two distinct mechanisms for the enhancement of plasma extravasation in the knee joint of the rat. One is activated by bradykinin and is neurogenic; the other is activated by platelet-activating factor and is non-neurogenic. Bradykinin-induced synovial plasma extravasation is known to be dependent on the sympathetic postganglionic neuron terminal, and to involve prostaglandins, ATP, adenosine A2 receptor action, and the attraction and activation of neutrophils. In this study we found that bradykinin-induced plasma extravasation also involves endothelium-derived relaxing factor; specifically we found that bradykinin induced plasma extravasation was antagonized stereospecifically by the inhibitor of endothelium-derived relaxing factor synthesis, NG-monomethyl-L-arginine. Perfused alone, platelet-activating factor produced an increase in synovial plasma extravasation which was markedly reduced by the platelet-activating factor receptor antagonists BN 52021 and WEB 2086 (these antagonists did not affect bradykinin-induced plasma extravasation). Platelet-activating factor-induced plasma extravasation was not affected by NG-monomethyl-L-arginine, indomethacin (a prostaglandin synthesis inhibitor), phenol 3-(5H-thiozolo[2,3b]quinazolin) (an A2 receptor adenosine antagonist), dextran sulfate (an inhibitor of leukocyte rolling), hydroxyurea (a depletor of leukocytes), chronic sympathectomy or the depletion of unmyelinated afferent fibers. Of note, the magnitude of platelet activating factor-induced plasma extravasation was increased by co-perfusion with prostaglandin E2 and attenuated by co-perfusion with L-arginine; that is, two of the mediators involved in neurogenic bradykinin-induced plasma extravasation exerted an influence on non-neurogenic plasma extravasation. Separate mechanisms for bradykinin and platelet-activating factor plasma extravasation were further demonstrated in the streptozotocin-treated diabetic rat, in which there is a peripheral neuropathy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450971 TI - Cytoplasmic segregation and cytoskeletal organization in the electric catfish giant electromotoneuron with special reference to the axon hillock region. AB - The cytoplasm of the highly polarized nerve cell is permanently segregated into domains with differing organellar composition. The mechanisms maintaining this segregation are largely unknown. In order to elucidate the potential role of cytoskeletal elements in this process we compared the cytoplasmic segregation within the giant electromotoneuron of the electric catfish (Malapterurus electricus) with the distribution of binding sites for antibodies against elements of the cytoskeleton. Most prominent cytoplasmic segregations include the formation of a subplasmalemmal cortical structure free of Nissl bodies and Golgi cisternae, the separation within the soma of domains containing rough endoplasmic reticulum and filament-rich domains, and the soma-axon transition. The cytoplasmic transition at the axon hillock forms a distinct borderline where Nissl bodies, Golgi cisternae and the bulk of lysosomes abruptly terminate and are excluded from the axoplasm. Synaptic vesicles and mitochondria are free to pass compartmental borders. Tropomyosin, spectrin, and alpha-actinin reveal a rather homogeneous immunofluorescence throughout the neuron. In contrast, neurofilament protein and tubulin display a distinctly increased immunofluorescence in the subplasmalemmal cortical layer, in dendrites as well as in the axon. The increase in immunofluorescence at the axon hillock exactly depicts the small transition zone from the somatic cytoplasm rich in Nissl bodies, Golgi cisternae and lysosomes to the differently structured axoplasm. The picture is similar for beta-tubulin, tyrosinylated and detyrosinylated alpha tubulin. Detyrosinylated tubulin (glu-tubulin, which is contained in microtubules of increased stability) shows the most prominent enrichment in the axon. The distribution of myosin is comparable to that of neurofilament protein but there is less difference in immunofluorescence between the domains. Our results would be compatible with a role of microtubules together with (the closely associated) neurofilaments in the segregation of neuronal cytoplasmic domains. Active transport as well as stable binding to the somatic cytoskeleton might counteract a homogeneous cytoplasmic distribution of the various classes of organelles by diffusion. PMID- 8450972 TI - Influence of muscle cell substrates on differentiation of intrafusal fiber types in neonatal rats. AB - Rat muscle spindles contain one nuclear bag2, one nuclear bag1, and two nuclear chain fibers. The three different types of intrafusal fiber in spindles may be a reflection of concomitant changes in proportions of slow primary, slow/fast secondary, and fast secondary myotubes during the period of spindle development. We examined whether experimentally altering the available muscle substrates would impact the intrafusal fiber type composition of spindles. De novo formation of spindles in muscles devoid of primary myotubes was induced by crushing the nerve to the medial gastrocnemius muscle in newborn rats and administering nerve growth factor for ten days afterwards. Encapsulated fibers of the reinnervated muscles examined one month after nerve crush had myofibrillar adenosine triphosphatase and myosin heavy chain profiles similar to normal bag2, bag1, or chain intrafusal fibers. However, spindles in reinnervated muscles contained fewer fibers than controls. Most experimental spindles contained chain and/or bag1 fibers, the two fiber types which ordinarily arise during secondary myogenesis. In contrast, bag2 fibers, fibers that normally form concomitant with primary myogenesis, were absent from nearly 90% of spindles in reinnervated muscles. The paucity of bag2 fibers may reflect the absence of primary myotubes, whereas the prevalence of chain and/or bag1 fibers may reflect that secondary myotubes or myofibers that descended from the secondary myotubes were the principal muscle substrates available for spindle formation in the nerve-crushed muscles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450973 TI - Mechanical hyperalgesia in streptozotocin-diabetic rats. AB - Recent evidence strongly suggests that the hyperalgesia induced by agents acting directly on the primary afferent is mediated by stimulatory G-proteins and the cAMP second messenger system. In this study, we used the Randall-Selitto paw pressure device to study hyperalgesia that develops in the streptozotocin diabetic rat. Subcutaneous injection of streptozotocin in male Sprague-Dawley rats induced hyperglycemia and glucosuria detectable within 24 h of injection. A decrease in mechanical nociceptive threshold in the hindpaw was detected after one week. Intradermal injection of indomethacin, a cyclooxygenase inhibitor, had no significant effect on nociceptive threshold; and prostaglandin E2, which produces hyperalgesia by a direct action on the primary afferent, decreased nociceptive threshold similarly in streptozotocin-diabetic and control rats. Guanosine 5'-O-(2-thiodiphosphate), which blocks stimulatory G-proteins, attenuated the prostaglandin E2-hyperalgesia in both streptozotocin-diabetic and control rats, but had no effect on baseline nociceptive threshold in either group. Intradermal injection of either 2',5'-dideoxyadenosine, an inhibitor of adenylate cyclase, or phosphodiesterase, which degrades cAMP, increased mechanical nociceptive threshold in streptozotocin-diabetic rats whilst not affecting mechanical nociceptive threshold in the control rats. Intradermal injection of 8-bromo cAMP, a membrane-permeable analog of cAMP, produced hyperalgesia of significantly greater magnitude in the streptozotocin-diabetic rats than the control rats. Intradermal injection of N6-cyclopentyl adenosine, an A1-type adenosine agonist, which can activate an inhibitory G-protein and decrease cAMP production, also increased nociceptive thresholds in streptozotocin diabetic rats. This effect was blocked by pertussis toxin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450974 TI - Indomethacin, an inhibitor of prostaglandin synthesis attenuates alteration in spinal cord evoked potentials and edema formation after trauma to the spinal cord: an experimental study in the rat. AB - The potential efficacy of indomethacin (a potent inhibitor of endogenous prostaglandin synthesis) on spinal cord-evoked potentials and edema formation occurring after a focal trauma to the spinal cord was examined in a rat model. The spinal cord evoked potentials were recorded in urethane-anesthetized male rats using monopolar electrodes placed epidurally over the T9 (rostral) and T12 (caudal) segments after stimulation of the ipsilateral right tibial and sural nerves. Reference electrodes were placed in the corresponding paravertebral muscles. The spinal cord evoked potential consisted of a small positive peak followed by a broad and high negative peak. Amplitudes and latencies of the maximal positive peak and the maximal negative peak were measured. The latencies and amplitudes 30 min before injury were used as references (100%). A complete loss was denoted as 0%. All the potentials were quite stable during 30 min of recording before injury. Infliction of trauma to the T10-T11 segments of the spinal cord with a sterile scalpel blade (about 5 mm longitudinal and 2 mm deep incision into the right dorsal horn extending to Rexed's laminae VII) in untreated animals resulted in an immediate depression of the rostral maximal negative peak amplitude (60-100%) which persisted during 5 h of recording. The latencies of the rostral as well as caudal maximal negative and positive peaks increased successively from 2 h post-trauma. In this group of animals, 5 h after injury the spinal cord water content in the traumatized segments was increased by more than 6% as compared with a group of uninjured animals. Pretreatment with indomethacin (10 mg/kg body weight i.p. 30 min before injury) markedly attenuated the immediate decrease in the maximal negative peak amplitude after injury, but did not influence the successive latency increase. However, the increase in the water content of the traumatized cord after 5 h was less pronounced compared with untreated injured rats. Our results show a beneficial effect of indomethacin on trauma-induced spinal cord evoked potential changes and edema formation. Prostaglandins may thus influence early bioelectrical changes occurring in traumatized spinal cord not reported earlier. The findings support the view that early recording of spinal cord evoked potential may be useful to predict the outcome in some forms of spinal cord injuries. PMID- 8450975 TI - Differentiation of a medulloblastoma cell line towards an astrocytic lineage using the human T lymphotropic retrovirus-1. AB - Constituent cells of medulloblastoma, the most common brain tumor occurring in childhood, resemble the primitive neuroepithelial cells normally found in the developing nervous system. However, mutational events prevent their further differentiation. We used the human T cell lymphotrophic virus type 1 to activate these deregulated immature cells by means of its transactivating protein Tax. Concomitant with viral infection was a decrease in cell proliferation characterized by inhibition of [3H]thymidine incorporation and in the number of cells in the G2/M phase of the cell cycle. Morphological changes suggested that medulloblastoma cells differentiated along the astrocytic lineage. The glial phenotype was confirmed by the induction of the glial fibrillary acidic protein and the glial enzyme glutamine synthetase. A direct viral effect and/or secondary effects to viral infection via paracrine/autocrine pathways could counterbalance the maturational defect in these medulloblastoma cells. PMID- 8450976 TI - Formation of the septohippocampal projection in vitro: an electron microscopic immunocytochemical study of cholinergic synapses. AB - Cholinergic neurons in the medial septum/diagonal band complex project to the hippocampus and fascia dentata and establish characteristic types of synapses on a variety of target neurons. At present we do not know the principles that underlie the development of this projection and the formation of the cholinergic synapses. Here we have used co-cultured slices of septum and hippocampus of one- to six-day-old rat pups to study the development of the septohippocampal pathway and the formation of cholinergic synapses on hippocampal target neurons in vitro. Slices of septum and hippocampus were incubated together for 10-46 days applying the roller-tube technique. The fluorescent dye dioctadecyltetramethylindocarbocyanine perchlorate and histochemical staining for acetylcholinesterase labeled many fibers connecting both explants. Combined light and electron-microscopic immunocytochemistry for choline acetyltransferase, the acetylcholine-synthesizing enzyme, revealed multipolar immunopositive neurons with long aspiny dendrites in the septal culture. Numerous varicose immunoreactive, supposedly cholinergic fibers could be followed from the septal to the hippocampal culture where they ramified and formed a three-dimensional network. As in situ, cholinergic terminals formed characteristic symmetric synapses on cell bodies, spines and, most often, on dendritic shafts of the hippocampal target neurons. No immunoreactive fibers and synapses were observed in single cultures of hippocampus. These results demonstrate that the cholinergic septohippocampal projection develops in vitro and that similar types of cholinergic synapses are established on co-cultured hippocampal target neurons as observed in situ. PMID- 8450977 TI - Reduced density of adenosine A1 receptors and preserved coupling of adenosine A1 receptors to G proteins in Alzheimer hippocampus: a quantitative autoradiographic study. AB - Binding to adenosine A1 receptors and the status of their coupling to G proteins were studied in the hippocampus and parahippocampal gyrus of Alzheimer individuals and age-matched controls. The binding to A1 receptors was compared with binding to the N-methyl-D-aspartate receptor complex channel-associated sites (labeled with (+)-[3H]5-methyl-10,11-dihydro-5H- dibenzo[a,d]cyclohepten 5,10-imine maleate). In vitro quantitative autoradiography demonstrated a similar anatomical distribution of A1 receptors labeled either with an agonist ((-) [3H]phenylisopropyladenosine) or antagonist ([3H]8-cyclopentyl-1,3 dipropylxanthine) in the brains of elderly controls. In Alzheimer patients, significant decreases in the density of both agonist and antagonist binding sites were found in the molecular layer of the dentate gyrus. Decreased A1 agonist binding was also observed in the CA1 stratum oriens and outer layers of the parahippocampal gyrus, while reduced antagonist binding was found in the subiculum and CA3 region. Reduced density of the N-methyl-D-aspartate receptor channel sites was found in the CA1 region and parahippocampal gyrus. The reductions in binding to adenosine A1 and N-methyl-D-aspartate receptors were due to a decrease in the density of binding sites (Bmax), and not changes in receptor affinity (KD). In both elderly control and Alzheimer subjects, GTP substantially reduced the density of A1 agonist binding sites with a concomitant increase in the KD values, whereas antagonist binding was unaffected by GTP. The results suggest that adenosine A1 receptor agonists and antagonists recognize overlapping populations of binding sites. Reduced density of A1 receptors in the molecular layer of the dentate gyrus most probably reflects damage of the perforant path input in Alzheimer's disease, while altered binding in the CA1 and CA3 regions is probably due to loss of intrinsic neurons. Similar effects of GTP on binding to A1 receptors in control and Alzheimer individuals suggest lack of alterations in coupling of A1 receptors to G proteins in Alzheimer's disease, thus supporting the notion of normal receptor coupling to their effector systems in Alzheimer's disease. PMID- 8450978 TI - A neurochemical and behavioral investigation of the involvement of nucleus accumbens dopamine in instrumental avoidance. AB - Two experiments were conducted to investigate the role of nucleus accumbens dopamine in the performance of a lever press avoidance task in the rat. In this task, 0.5 mA shock was presented for 5 s every 30 s, but the rat could escape shock presentation, or avoid the shock for 30 s, by pressing a lever. In the first experiment, dialysis probes were implanted into the nucleus accumbens of rats previously trained on the avoidance procedure, and also two groups of untrained rats. On the day after dialysis probe implantation, rats trained to press a lever to avoid shock (n = 10) were exposed to a 45 min avoidance test session. Untrained rats were either exposed to periodic shock (n = 9) or the control procedure in which lights were dimmed but no shock was presented (n = 8). Performance of the avoidance task led to significant increases in extracellular dopamine and dopamine metabolites. There was a significant positive correlation between increases in extracellular dopamine and the number of avoidance responses emitted. In the second experiment, groups of rats were trained on the lever press avoidance procedure. After training, rats received intra-accumbens injections of the neurotoxic agent 6-hydroxydopamine or ascorbic acid vehicle. Dopamine depletion produced by 6-hydroxydopamine injection led to a substantial decrease in lever pressing to avoid or escape shock. These results indicate that dopamine in nucleus accumbens is important for operant avoidance responding, and that the involvement of accumbens dopamine in instrumental behavior is not unique to positively reinforced responses. PMID- 8450979 TI - Amplification of rewarding hypothalamic stimulation following a unilateral lesion in the region of the tuberomammillary nucleus. AB - The tuberomammillary nucleus, a cluster of cells in the posterior hypothalamus, is the only known source of brain histamine. Although this nucleus is well described in terms of anatomy and neurochemistry, only little is known about its function. In the present study, the effect of a lesion in the region of this nucleus on intracranial self-stimulation was examined. Rats were implanted bilaterally with stimulating electrodes in the lateral hypothalamus and unilaterally with one lesion electrode in the region of this nucleus. After three days of baseline testing, half of the animals were given an electrolytic lesion. The animals were retested for six consecutive days, and thereafter weekly for another seven weeks. From the second day postlesion on, we unexpectedly found a gradual increase in response rate, which peaked on day 13 in the ipsilateral hemisphere only. Although there was no further increase over subsequent days, response rates remained elevated during the following seven weekly tests. The observed increase in lateral hypothalamic self-stimulation after an electrolytic lesion of the tuberomammillary nucleus is discussed in terms of an inhibitory system, possibly located in the region of this nucleus which, when removed by the lesion, increased reinforcing effects of the electrical brain stimulation. The fact that the effects on self-stimulation were lateralized to one hemisphere rules out an interpretation in terms of unspecific "performance" variables that could influence rate of lever pressing. PMID- 8450980 TI - Binocular matching in monkey visual cortex: single cell responses to correlated and uncorrelated dynamic random dot stereograms. AB - This paper presents results obtained from experiments performed on two behaving monkeys (Macaca mulatta) viewing correlated and uncorrelated dynamic random dot stereograms. Extracellular single unit activity was recorded from areas V1 and V2. We found that cells sensitive to correlated stereograms (38%) were also sensitive to uncorrelated stereograms. Regarding their response to both situations, these cells were grouped into two types. The first type (57%), termed "correlation-sensitive cells", responded with statistically significant difference to correlated and uncorrelated stereograms. The second type responded equally to both stereograms (43%), and therefore they were termed "correlation insensitive cells". Our data suggest that these two types may form two populations with different functions subserving depth perception. PMID- 8450981 TI - Serotonin-evoked modifications of the neuronal firing rate in the superior vestibular nucleus: a microiontophoretic study in the rat. AB - Microiontophoretic ejection (10-100 nA) of serotonin (5-hydroxytryptamine) into the superior vestibular nucleus induced modifications of the mean firing rate in 87% of the neurons examined. The responses to 5-hydroxytryptamine application were excitatory in 48% of the cells, inhibitory in 29%, and biphasic (inhibitory/excitatory) in the remaining 10%. The excited neurons were scattered throughout the nucleus; the units inhibited or characterized by biphasic responses were distinctly more numerous in the ventrolateral sector of the nucleus. The magnitude of both excitatory and inhibitory effects was dose dependent. The excitatory responses to 5-hydroxytryptamine were blocked or greatly reduced by two 5-hydroxytryptamine antagonists, methysergide and ketanserin, or even reversed in many cases. Inhibitory responses were enhanced by simultaneous application of 5-hydroxytryptamine antagonists in half of the units studied. In the remaining units, ketanserin left the response unmodified, whereas methysergide reduced but never quite blocked it. The application of 5-methoxy-N,N dimethyltryptamine, a 5-hydroxytryptamine agonist more effective on 5 hydroxytryptamine1 than on 5-hydroxytryptamine2 receptors, and of 8-hydroxy-2(di n-propyl-amino) tetralin, a 5-hydroxytryptamine1A-specific agonist, induced a decrease in the firing rate which was unaffected by methysergide. These results support the hypothesis that 5-hydroxytryptamine exerts various functions throughout the superior vestibular nucleus by various receptors and that the inhibitory action is limited to an area of it.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8450982 TI - Sites of transmitter release and relation to intracellular Ca2+ in cultured sympathetic neurons. AB - Fluorescence imaging of indo-1 loaded cells was used to monitor influx and distribution of Ca2+ in cell bodies, neurites and growth cones of sympathetic neurons cultured from embryonic chick. Similar experiments on release of tritiated noradrenaline were performed to assess the relationship between intracellular Ca2+ concentration ([Ca2+]i) and transmitter release. Effects of Ca2+ channel antagonists on electrically stimulated rise in [Ca2+]i were dependent on the neuronal region examined. Cadmium and verapamil blocked Ca2+ entry in cell bodies but were less effective in neurites and growth cones. Nifedipine partially inhibited Ca2+ entry in cell bodies and was less effective in neurites and growth cones. Combination of cadmium and nifedipine blocked [Ca2+]i rise in all neuronal regions. Omega-conotoxin was an effective Ca2+ channel blocker in all regions. Ca2+ channel blockers had effects on [3H]noradrenaline release which paralleled effects on [Ca2+]i in neurites (and growth cones) but not cell bodies. Cadmium, verapamil and nifedipine each caused a partial, reversible block of the evoked release. Combination of cadmium and nifedipine completely blocked evoked [3H]noradrenaline release. Omega-conotoxin caused complete, irreversible block of electrically evoked release. During prolonged depolarization with 125 mM K+ Krebs solution, elevation of [Ca2+]i was maintained in cell bodies but was transient in neurites and growth cones. The amplitude and time course of [3H]noradrenaline release paralleled [Ca2+]i in neurites and growth cones, but not the cell body under the above conditions. A new method is described to study localized uptake and release of [3H]noradrenaline in cell bodies versus neurites of sympathetic neurons. Incubation of these modified cultures with [3H]noradrenaline showed that cell bodies had very low [3H]noradrenaline uptake (0.23 x 10(-6) c.p.m./mg protein), whereas neurites contained approximately 20 times more radioactivity. Depolarization of neurites by excess K+ and field stimulation caused a large increase in the net release of [3H]noradrenaline. The release was unaffected by removal of cell bodies. Neurites remained functionally viable for more than 2 h after separation from their cell bodies. [3H]Noradrenaline release could be evoked repeatedly over this time. [3H]Noradrenaline release from isolated neurites was partially blocked by nifedipine and fully blocked by combination of cadmium and nifedipine or by omega-conotoxin. The uptake and release of [3H]noradrenaline by neurites alone (expressed per mg protein) accounted for the total [3H]noradrenaline in intact cultures with neurites and cell bodies. Therefore, we conclude that neurites (and growth cones) are the prominent sites of uptake, storage and release of sympathetic transmitter.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8450983 TI - Acetylcholine receptor bars and transmitter release in frog neuromuscular junctions. AB - After labelling with rhodaminated alpha-bungarotoxin, acetylcholine receptors in cutaneous pectoris muscles of normal adult frogs (Rana temporaria) appear as brightly fluorescent straight bars, usually extending over the whole gutter. Here we investigated first whether receptor bars can undergo changes and secondly whether they would provide a structural correlate for the strength of a junction. Bars of low fluorescence intensity, as well as short or discontinuous receptor bars consisting of two or three segments, suggest plasticity at the receptor/active zone level. In order to elucidate this notion, receptor bars were studied at different seasons which have previously been shown to be associated with structural changes. In two groups of frogs kept under laboratory conditions simulating wintertime and summertime, respectively, the length and number of receptor bars and the amount of discontinuous bars were investigated. Synaptic contact length, which is the summed length of labelled synaptic branches, and the number and total length of receptor bars did not differ significantly. A clear difference between Group I ("winter" frogs) and Group II ("summer" frogs) was found in the number of discontinuous bars, which was almost twice as high in Group I compared with Group II (6.4 +/- 3.3% S.D. vs 3.4 +/- 1.3% S.D., n = 8 and 7 muscles, respectively, P < 0.05). In addition, the average length of individual bars was slightly longer in Group I frogs (2.16 +/- 0.7 micron S.D. vs 2.07 +/- 0.12 microns S.D., 0.1 < P < 0.05). Transmitter release has been shown to be different in these two groups--as determined from endplate potential measurements in tubocurarine-containing bathing solutions--although it was equal when measured in low Ca2+/high Mg2+ [Dorlochter M. et al. (1991) Pflugers Arch. 418, Suppl. 1, R31]. We also investigated whether receptor bars would be a reasonable structural correlate of synaptic function by comparing different measures of transmitters release with different structural parameters in 19 identified junctions. The mean quantal content (m) of a junction was positively correlated with the number and total length of receptor bars, but not with synaptic contact area or length. Amplitudes of the first, maximum, and plateau endplate potentials (corrected for a common resting potential and apparent input resistance) at tetanic nerve stimulation (40 Hz for 2 s) in tubocurarine block were strongly correlated with both synaptic contact length and total receptor bar length (r = 0.90 for maximum endplate potential); correlations between m and any structural measure were significantly worse.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8450984 TI - Acute hypertension after stroke: the scientific basis for treatment decisions. PMID- 8450985 TI - Laboratory monitoring of oral anticoagulant therapy: are we being misled? PMID- 8450986 TI - Postoperative brainstem and cerebellar infarcts. AB - OBJECTIVE: To study the clinical features and causes of postoperative brainstem and cerebellar infarcts. METHODS: Two groups were studied. The 10 group 1 patients had cardiac (eight) or aortic (two) surgery. The 12 group 2 patients had noncardiac-nonvascular surgery, including orthopedic (five), gynecologic (four), and general (three). Patients were studied by stroke services at university hospitals in Boston (13), Charlottesville (three), Baltimore (three), and Mainz (three) during 2 consecutive years. RESULTS: Onset of strokes was immediately postoperative (six), during the first 48 postoperative hours (nine), and delayed 3 days or more (seven). Clinical syndromes were altered level of consciousness or cognition (15), vestibulocerebellar (four), and hemiparesis with focal brainstem signs (three). Infarction involved the brainstem (13), cerebellum (13), and posterior cerebral artery hemispheric territory (10). Causes: In group 1, five infarcts were due to cardiogenic embolism and three to embolism from the aorta. One patient had a postoperative pontine lacunar infarct and one developed an infarct in the territory of a known stenotic basilar artery. In group 2, one patient had vertebral artery injury from instrumentation, one had medical complications with severe hemorrhage and hypotension, and 10 most likely had position-related vertebral artery thromboses. CONCLUSIONS: Patients with postoperative brainstem and cerebellar infarcts present with altered consciousness or vestibulocerebellar syndromes. The major cause of brain infarcts after cardiac surgery is embolism from the heart and aorta. The causes of infarction after general surgery are less clear, but neck positioning during or after surgery may play an important role by promoting thrombi in compressed arteries that later embolize intracranially when neck motion becomes free. PMID- 8450987 TI - Randomized clinical trial on the efficacy of antiepileptic drugs in reducing the risk of relapse after a first unprovoked tonic-clonic seizure. First Seizure Trial Group (FIR.S.T. Group) AB - We conducted a randomized multicenter clinical trial on 397 patients ranging in age from 2 to 70 years to assess the effectiveness of treatment of the first unprovoked epileptic seizure. Subjects seen within 7 days after a first witnessed tonic-clonic seizure with or without partial onset were randomized to immediate treatment (carbamazepine, phenytoin, phenobarbital, or sodium valproate) or to treatment with the same drugs only after seizure recurrence. We excluded individuals with acute symptomatic seizures, progressive neurologic disorders, or gross psychiatric illness. Thirty-six of 204 subjects randomized to treatment and 75 of 193 randomized to delayed treatment experienced seizure recurrence during follow-up. The cumulative time-dependent risk of relapse among treated subjects was 25% by 24 months. The corresponding figure for untreated subjects was 51%. The risk of relapse was 2.8 times higher (95% CI, 1.9 to 4.2) for untreated subjects. There were no interactions between age and EEG findings (the only predictors of risk of relapse) and treatment effects. We conclude that treatment of the first seizure with antiepileptic drugs leads to a significant reduction of the risk of relapse. PMID- 8450988 TI - Status epilepticus at an urban public hospital in the 1980s. AB - We retrospectively reviewed the clinical course of adult patients treated for generalized status epilepticus (SE) at the San Francisco General Hospital (SFGH) from 1980 to 1989. The review was designed to determine whether the etiologies of SE at our hospital have changed over the last two decades, and to investigate the relationships between etiology, response to anticonvulsant therapy, and short term clinical outcome. Of 154 patients reviewed, the four leading etiologies for SE were anticonvulsant drug withdrawal (39), alcohol-related (39), drug toxicity (14), and CNS infection (12). This pattern was essentially unchanged from observations made at SFGH in the 1970s. Sixty percent of all patients responded to first-line drug treatment (usually phenytoin +/- diazepam), and the remainder required an additional agent (usually phenobarbital) for control of SE. The best response to anticonvulsants occurred in patients with SE related to tumor, anticonvulsant drug withdrawal, or refractory epilepsy, and the poor responders had anoxia, drug toxicity, CNS infection, or other metabolic abnormalities. Seventy-six percent of the patients had good outcomes. Of the 22 patients who died, SE was a likely cause of death in only two (ie, 1.3% of the entire study group). Metabolic abnormalities, stroke, and anoxia were associated with particularly poor outcomes compared with other etiologies. These observations show that the etiologies of SE have remained similar over two successive decades, and that the etiology of SE may help predict both the initial response to drug therapy and the short-term outcome. PMID- 8450989 TI - New-onset seizures in an elderly hospitalized population. AB - We studied 80 hospitalized patients over 60 years old with either new-onset or newly diagnosed seizures that were generalized tonic-clonic in approximately half the cases and partial with or without secondary generalization in the other half. The etiology of seizures was acute symptomatic in 33 (41%), remote symptomatic in 32 (40%), progressive encephalopathy in nine (11%), and idiopathic in six (8%). Convulsive status epilepticus occurred in five cases (6%). The most common single cause of seizures was infarction or hemorrhage (54%). Morbidity and mortality were highest in the acute symptomatic group (p < 0.03). Nine (11%) of the subjects died within 3 months of admission, including two of the five with status epilepticus. Of the patients with acute symptomatic etiologies, 21% died compared with 6% of those in the remote symptomatic group. New neurologic deficits were present in eight (11%) of the 71 who survived, including five acute symptomatic, one remote symptomatic, and two progressive encephalopathy cases. No patient with idiopathic seizures died or had new neurologic deficits. We conclude that seizures in the elderly requiring hospitalization occur mainly with acute and remote symptomatic neurologic insults and are associated with a significant morbidity and mortality. In the absence of any associated neurologic insults, the morbidity is low. PMID- 8450990 TI - Electrophysiologic detection of extrapyramidal motor signs in Alzheimer's disease. AB - We applied quantitative methods to measure extrapyramidal signs in 50 Alzheimer's disease (AD) patients and 40 age-matched control subjects. We measured tremor using accelerometers, bradykinesia using computer-detected reaction times (RTs) and movement times (MTs), and rigidity using a strain gauge linked to a movable arm rest. We excluded subjects with a clinical diagnosis of Parkinson's disease and subjects who required antiparkinsonian, neuroleptic, or anxiolytic medications. Aside from rigidity in two patients, there were no extrapyramidal signs on clinical examination. Based on electrophysiologic measures, however, there was a significant increase in muscle tone (p < 0.001), RT (p < 0.01), and MT (p < 0.03) in AD patients as a group compared with control subjects. Within the AD group, muscle tone and MTs increased across clinical stages of dementia severity (p < 0.05). Tremor frequency and amplitude were normal in AD subjects. These data indicate that quantitative neurophysiologic measures are superior to conventional clinical examinations in detecting extrapyramidal signs in AD. The pathologic substrates of extrapyramidal signs in AD are uncertain but seem to be linked to the degenerative AD process. PMID- 8450991 TI - Dopamine-related personality traits in Parkinson's disease. AB - Studies suggest that Parkinson's disease (PD) is associated with a particular group of personality characteristics. With relative uniformity, PD patients are described as industrious, rigidly moral, stoic, serious, and nonimpulsive. In this controlled study, we used a recently developed personality questionnaire, Cloningers's Tridimensional Personality Questionnaire, to test the hypothesis that these personality traits are behavioural manifestations of damaged dopaminergic pleasure and reward systems. We found significantly less (p < 0.01) of a group of traits called "novelty seeking" in PD patients compared with matched medical controls. Patients with low novelty seeking are described as being reflective, rigid, stoic, slow-tempered, frugal, orderly, and persistent, characteristics similar to those in the clinical description of PD patients. We review evidence supporting the claim that novelty seeking is dopamine-dependent, and suggest that damage to the mesolimbic dopaminergic system causes the described personality profile of PD patients. PMID- 8450992 TI - Reduced brain N-acetylaspartate suggests neuronal loss in cognitively impaired human immunodeficiency virus-seropositive individuals: in vivo 1H magnetic resonance spectroscopic imaging. AB - We used magnetic resonance imaging (MRI) and water-suppressed proton magnetic resonance spectroscopic imaging to study the effects of human immunodeficiency virus (HIV) infection on the brains of 10 individuals with cognitive impairment due to HIV and seven normal controls. 1H spectra from nine 2.5-ml volumes in the centrum semiovale and the mesial cortex showed significantly reduced N acetylaspartate (NAA) relative to choline and creatine in the cognitively impaired HIV-infected subjects. This reduction was due to a nonlocalized decrease of NAA in these patients, only two of whom had moderate atrophy and white matter signal hyperintensities on MRI. Since NAA is a putative neuronal marker, the findings suggest neuronal damage in early stages of HIV infection that is not evident on standard MRI and are consistent with the neuropathologically known neuronal loss. PMID- 8450993 TI - Incidence of dementia and probable Alzheimer's disease in a general population: the Framingham Study. AB - OBJECTIVE: To determine the incidence of dementia and Alzheimer's disease (AD) in a general population sample. BACKGROUND: Utilizing subjects in the Framingham Study cohort determined to be free of dementia in 1976 to 1978, or on biennial examination 17 in 1982, all new cases of dementia arising in this cohort over a maximum of 10 years of follow-up were ascertained. METHODS: On biennial examination 14/15, a screening neuropsychologic examination was administered to 2,117 subjects, and cases of probable prevalent dementia were identified. Beginning on examination 17 and on all successive biennial examinations, a Mini Mental State Examination was administered. Subjects previously free of dementia and falling below age-education levels were evaluated by a neurologist and neuropsychologist to determine if dementia was present and to ascertain the dementia type using standard criteria. RESULTS: Five-year incidence of dementia increased with age, doubling in successive 5-year age groups. Dementia incidence rose from 7.0 per 1,000 at ages 65 to 69 to 118.0 per 1,000 at ages 85 to 89 for men and women combined. Incidence of probable AD also doubled with successive quinquennia from 3.5 at ages 65 to 69 to 72.8 per 1,000 at ages 85 to 89 years. Incidence of dementia and of probable AD did not level off with age and was not different in men and women. CONCLUSIONS: In a general population sample, we determined incidence of dementia and of probable AD and will use these incident cases for study of precursors and natural history in this elderly cohort, which has been under close surveillance for over 40 years. PMID- 8450994 TI - Duchenne dystrophy: randomized, controlled trial of prednisone (18 months) and azathioprine (12 months) AB - Prednisone has been shown to improve strength in Duchenne dystrophy. Azathioprine often benefits corticosteroid-responsive diseases and can reduce the dose of prednisone needed. The present study reports a randomized, controlled trial of prednisone and azathioprine designed to assess the longer-term effects of prednisone and to determine whether azathioprine alone, or in combination with prednisone, improves strength. Ninety-nine boys (aged five to 15 years) with Duchenne dystrophy were randomized to one of three groups: (I) placebo; (II) prednisone 0.3 mg/kg/d; or (III) prednisone 0.75 mg/kg/d. After 6 months, azathioprine 2 to 2.5 mg/kg/d was added in groups I and II and placebo added in group III. The study showed that the beneficial effect of prednisone (0.75 mg/kg/d) is maintained for at least 18 months and is associated with a 36% increase in muscle mass. There was weight gain, growth retardation, and other side effects. Azathioprine did not have a beneficial effect. This study suggests that prednisone's beneficial effect is not due to immunosuppression. PMID- 8450995 TI - Cyclosporine increases muscular force generation in Duchenne muscular dystrophy. AB - We investigated the effect of cyclosporine (CsA) on force generation in 15 boys with Duchenne muscular dystrophy (DMD) by obtaining monthly measures of tetanic force and maximum voluntary contraction (MVC) of both anterior tibial muscles. During 4 months of a natural history phase, both tetanic force and MVC declined significantly. During 8 weeks of CsA treatment (5 mg/kg/day), significantly increased tetanic force (25.8 +/- 6.6%) and MVC (13.6 +/- 4.0%) occurred within 2 weeks. The maximum mean increase during treatment was 35.2 +/- 5.9% (tetanic force) and 19.0 +/- 4.6% (MVC). Side effects from CsA, gastrointestinal and flu like symptoms, were transient and self-limiting. Thus, as previously reported with prednisone, CsA increases muscular force generation in the anterior tibial muscles of DMD patients. PMID- 8450996 TI - Mononuclear cell analysis of muscle biopsies in prednisone- and azathioprine treated Duchenne muscular dystrophy. AB - Prednisone improves strength and function in patients with Duchenne dystrophy. Although the mechanism of this effect is uncertain, prior studies suggested that the benefit might result from immunosuppressive effects on T lymphocytes invading muscle. A recent randomized, double-blind, controlled trial of prednisone and azathioprine demonstrated that azathioprine had no effect in Duchenne dystrophy, raising questions about the role of immunosuppression in mediating clinical improvement. The goal of this current study was to compare the effects of prednisone and azathioprine on mononuclear infiltrates from biopsies performed at the end of the controlled clinical trial (reported separately in the article by Griggs et al on page 520). We studied 14 patients from the prednisone group (0.75 mg/kg/d), 10 from the combination therapy group (prednisone 0.3 mg/kg/d and azathioprine 2.5 mg/kg/d), and 13 from the azathioprine group (2.5 mg/kg/d), and used monoclonal antibodies for cell typing. There were no significant differences between the groups for total T cells, T-cell subsets, B cells, natural killer cells, total mononuclear cells, necrotic muscle fibers, or fibers focally invaded by mononuclear cells. These data indicate that azathioprine decreases mononuclear subsets infiltrating muscle to a similar degree as does prednisone, although azathioprine-treated patients do not show a clinical improvement. This implies that immunosuppressive actions on cellular infiltrates in muscle are probably not the primary mechanism of prednisone-induced clinical improvement. PMID- 8450997 TI - High-dose intravenous immunoglobulin therapy in multifocal motor neuropathy. AB - We treated five consecutive patients with multifocal motor neuropathy (MMN) with high-dose intravenous immunoglobulin (IVIg). Four patients had increased levels of anti-asialo-GM1 IgM and two of anti-GM1 IgM as well; one patient had no reactivity. We treated them twice with 0.4 g/kg IVIg for 5 consecutive days at a 2-month interval, followed by maintenance infusions up to 6 to 12 months. All patients with high anti-asialo-GM1 had a consistent clinical improvement starting 3 to 10 days after the first IVIg course; in one patient, recovery was complete and persistent for 12 months without additional treatment, while in three patients, improvement only lasted 20 to 30 days. There was a similar improvement in these patients after the second course of IVIg which was maintained by periodic 2-day IVIg infusions. Clinical improvement in these patients was associated with a reduction of conduction block in most, but not all, motor nerves, while antibody titers were not consistently modified by treatment. There was no clinical or electrophysiologic improvement in the patient without antiglycolipid activity after 6 months of IVIg. IVIg may be a safe and effective therapy for MMN. PMID- 8450998 TI - Low-dose apomorphine challenge in tardive akathisia. AB - We challenged seven tardive akathisia patients with low-dose apomorphine (0.01 mg/kg) SC and placebo in a double-blind, random design. Apomorphine caused a significantly greater reduction in the objective (movement) but not the subjective (distress) component of akathisia. PMID- 8450999 TI - HLA-DQA1 and -DQB1 associations with multiple sclerosis in Sardinia and French Canada: evidence for immunogenetically distinct patient groups. AB - We analyzed the association of HLA-DQA1 and -DQB1 alleles with multiple sclerosis (MS) in a collaborative study of 116 Sardinian and 75 French Canadian MS patients by the relative predispositional effect method. In French Canadians, MS was positively associated with DQA1*0102 and DQB1*0602, but there was no positive association of either allele with Sardinian MS, which, by contrast, was positively associated with DQB1*0302 and *0201 and with DQA1*0301, whereas none of these alleles was MS-associated in French Canadians. In comparison with French Canadian results, DQA1*0102 was protective against MS in Sardinians. We suggest that DQA1*0102 has no MS predispositional role in French Canadians, but is MS associated because it is in linkage disequilibrium with true predispositional alleles present within the DQB1*0602-bearing haplotype. Whereas DQB1 alleles encoding leucine (Leu) at residue 26 showed a strong MS association in French Canadians (relative risk = 24.7), there was no correlation with DQ beta Leu26 in Sardinian MS. No other DQA1 or DQB1 codons showed a positive disease correlation in both groups. Together the data suggest that the two MS patient groups are immunogenetically distinct, and it may be impossible to formulate a unifying hypothesis that explains the different MS-class II associations in these and other ethnic groups. PMID- 8451000 TI - Nigral dysfunction in drug-induced parkinsonism: an 18F-dopa PET study. AB - We studied 13 patients with severe drug-induced parkinsonism (DIP) using L-6 [18F]fluorodopa positron emission tomography (18F-dopa PET) to investigate the integrity of their dopaminergic nigrostriatal projections. Twelve of these patients were subsequently followed clinically for a median of 23.5 months (range, 6 to 49). Nine patients had normal putamen 18F-dopa uptake. In eight of these nine patients where follow-up was available, a normal 18F-dopa PET study was predictive of subsequent improvement of parkinsonism. Four of 13 DIP patients (31%) had significantly reduced putamen 18F-dopa uptake, within the Parkinson's disease range, and in three of these four (75%), this reduction was associated with continued, or worsening, parkinsonism. There were no clinical features at the time of PET that distinguished those who recovered and those who did not. We conclude that a normal 18F-dopa PET study correlates well with improvement from DIP, but an abnormal study does not necessarily indicate a poor prognosis. PMID- 8451001 TI - High-titer selective serum anti-beta-tubulin antibodies in chronic inflammatory demyelinating polyneuropathy. AB - Although chronic inflammatory demyelinating polyneuropathy (CIDP) is presumed to be an autoimmune disorder, no neural antigen has been recognized as an immune target. We found that serum IgM from a patient with CIDP and an IgM paraprotein reacted with a 53-kd protein by Western blot analysis. Amino acid sequence analysis identified this protein as beta-tubulin. We then studied sera from 70 CIDP patients, 35 Guillain-Barre syndrome (GBS) patients, and 483 disease (amyotrophic lateral sclerosis, Alzheimer's disease, multiple sclerosis, diabetes, and other polyneuropathies) and normal controls for selective high titer anti-beta-tubulin using ELISA methodology. Forty-two percent (30/70) of patients with CIDP had selective high titer IgM reactivity against beta-tubulin; 23% (16/70) had selective high-titer IgG reactivity against beta-tubulin. Overall, 57% of CIDP patients, 20% of GBS patients, and 2% of control patients had selective, high serum IgM or IgG anti-beta-tubulin reactivity. Selective high titer serum anti-beta-tubulin antibodies occur in a majority of patients with CIDP but are rare in other chronic neuropathies or CNS disorders. PMID- 8451002 TI - Perceptual analysis of speech disorders in progressive supranuclear palsy. AB - We used oral motor examinations and quantitative perceptual speech analysis to study deviant speech dimensions in 44 patients with progressive supranuclear palsy (PSP). All patients had dysarthria with variable degrees of spasticity, hypokinesia, and ataxia; 28 patients had all three of these components, and 16 patients had only two components. Twenty-two patients (50%) had predominantly spastic components, 15 (34%) had predominantly hypokinetic components, six (14%) had predominantly ataxic components, and in one (2%) the spastic, hypokinetic, and ataxic components were equal. Stuttering occurred in nine patients (20%) and palilalia in five (11%). The finding of a mixed dysarthria with a combination of spastic, hypokinetic, and ataxic components might assist in diagnosis and is consistent with the widespread neuropathologic changes found in PSP. PMID- 8451003 TI - Sensory aprosodia: a clinical clue to lesions of the inferior division of the right middle cerebral artery? AB - Isolated infarction in the territory of the inferior division of the right middle cerebral artery (MCA) is often associated with subtle clinical features. Sensory aprosodia, a disorder of emotional speech (affective prosody) with impaired prosodo-affective comprehension and repetition (but relatively spared expression) and added impairment of identification of emotional gesturing, has been advanced as a potential clinically useful marker for such lesions. We examine this hypothesis in a prospective serial study of native Anglophones with a recent initial unilateral cerebral infarction demonstrated on CT. There were four patients with inferior divisional infarctions of the right MCA among 42 with infarctions involving the MCA territory (27 right, 16 left). Sensory aprosodia was present acutely in four patients: two inferior divisional right MCA lesions, one more extensive right MCA lesion (with neurologic signs consistent with predominant inferior division of right MCA impairment), and one left MCA infarction. At approximately 20 days postinfarction, there were three patients with sensory aprosodia, including two with inferior divisional right MCA lesions and another with superior divisional right MCA infarction. No healthy controls or lacunar infarction patients showed this profile. We conclude that sensory aprosodia (1) is identifiable with standardized, objective methodology, (2) is an acute marker of inferior divisional infarction in the right MCA territory, (3) is less specific several weeks after infarction, and (4) is not associated with lacunar infarction. PMID- 8451004 TI - Enzyme immunoassay of anti-human acetylcholine receptor autoantibodies in patients with myasthenia gravis reveals correlation with striational autoantibodies. AB - Anti-acetylcholine receptor (AChR) autoantibodies are a marker of acquired myasthenia gravis (MG). Some of these antibodies cause muscle weakness. Striational autoantibodies (StrAb) also are a marker of MG. They are most prevalent in older patients and patients with thymoma. Here we describe a reproducible enzyme immunoassay (AChR-EIA) for detecting antibodies reactive with human muscle AChR, using antigens concentrated on plastic by prior sequential application of a biotinylated carrier, avidin, and biotinylated monoclonal IgG against AChR. There was significant correlation between values for antibodies assayed by AChR-EIA and by immunoprecipitation of AChR complexed with 125I-alpha bungarotoxin. Unexpectedly, AChR-EIA and StrAb values also were significantly correlated. Further studies revealed a significant and unprecedented correlation for StrAb and AChR precipitating antibodies. A plausible explanation for these findings is that some StrAb may react with cytoskeletal proteins that associate and copurify with AChR. The AChR-EIA offers a nonradioactive method for detecting two autoantibodies that are relatively restricted to patients with acquired MG. PMID- 8451005 TI - Reversible diencephalic dysfunction: episodic hyperhidrosis due to a trapped third ventricle. AB - We present a patient with episodic hyperhidrosis (EH) who had 15 attacks per day for 3 years following placement of a lateral ventricular shunt. MRI revealed that she had an isolated third ventricle. Stereotactic shunting of the third ventricle resulted in immediate and complete resolution of her symptoms. We suggest that this patient had periodic rises in third ventricular pressure resulting in episodic diencephalic dysfunction and EH. PMID- 8451006 TI - Retinotopic and directional deficits of smooth pursuit initiation after posterior cerebral hemispheric lesions. AB - We investigated the initiation of ocular smooth pursuit with horizontal ramp targets in 16 patients with unilateral posterior cerebral lesions. Four of the 16 patients had directional pursuit asymmetry, in which smooth eye movement velocities were reduced toward the lesion, independent of target location on the retina. Of seven patients with normal visual fields for the target, two had a retinotopic eye movement deficit consisting of impaired smooth pursuit of targets moving in both horizontal directions in the hemifield contralateral to their lesion. Patients with retinotopic deficits and normal visual fields, and those with directional deficits, had impairment of smooth pursuit similar to that caused by unilateral lesions of cortical areas MT (middle temporal) and MST (medial superior temporal) in monkeys. All but one patient with either of these defects had a lesion near the junction of Brodmann's areas 19, 37, and 39, providing evidence that this region includes the human homologues of monkey areas MT and MST. One patient with a retinotopic pursuit defect and normal visual fields had a lesion of the rostral superior temporal sulcus, which may have included the homologue of the superior temporal polysensory area of monkeys. PMID- 8451007 TI - Expression of major histocompatibility complex antigens in cultures of clonally derived human myoblasts. AB - We examined class I and class II HLA antigen expression by flow cytometry in clonal cultures derived from normal human skeletal muscle biopsies. Both HLA class I and class II antigens were constitutively expressed in all clones studied. By altering the constituents of the culture medium, we could modulate the expression of HLA class II but not HLA class I antigens. We noted heterogeneity in the expression of HLA class II antigens among different clones; an increased expression was associated with an increased propensity of myoblasts to fuse. These findings indicate that normal aneurally cultured myoblasts may express both HLA class I and class II antigens, that this expression may be modulated by in vitro agents, and that the presence of these antigens may relate to the process of in vitro myoblast fusion. PMID- 8451008 TI - Dural enhancement and cerebral displacement secondary to intracranial hypotension. AB - We studied a patient with spontaneous intracranial hypotension whose gadolinium enhanced MRI revealed an extraordinary degree of dural enhancement and striking displacement of the optic chiasm, flattening of the pons, and downward displacement of the cerebellar tonsils. These changes were reversed when a CSF leak at the site of a T12-L1 arachnoid cyst was closed following an epidural blood patch. Such diffuse meningeal enhancement results from the dural venous dilatation that accompanies a reduced CSF volume, a consequence of the Monro Kellie rule. PMID- 8451009 TI - Aspartame use in Parkinson's disease. AB - The artificial sweetener aspartame (NutraSweet) is hydrolyzed in the gut as phenylalanine (PA), a large neutral amino acid (LNAA). LNAAs compete with levodopa for uptake into the brain. To determine the effect of aspartame on levodopa-treated Parkinson's disease (PD) patients, we studied 18 PD patients with protein-sensitive motor fluctuations by administering in a double-blind and single-crossover design, on alternate days, aspartame (600 or 1,200 mg) and placebo. Every hour, we performed a motor examination and drew blood to estimate plasma LNAA, PA, and levodopa levels. Six-hundred mg of aspartame had no effect on plasma PA or motor status. Although 1,200 mg of aspartame significantly increased plasma PA, motor performance did not deteriorate. Aspartame consumption in amounts well in excess of what would be consumed by heavy users of aspartame sweetened products has no adverse effect on PD patients. PMID- 8451010 TI - Controlled study of the antiparkinsonian activity and tolerability of cabergoline. AB - Cabergoline, a new ergoline derivative, is a D2-specific dopaminergic agonist that is more potent and longer-acting than other agonist agents. We conducted a randomized, double-blind study of increasing doses of cabergoline taken once a day. Twenty-five patients with Parkinson's disease taking stable doses of levodopa began cabergoline at 0.5 mg. The dose was escalated at weekly intervals to 1.0 mg in 19 patients, 1.5 mg in 14 patients, 2.0 mg in nine patients, and 2.5 mg in four patients. Treatment continued for 8 weeks after titration. Unified Parkinson's Disease Rating Scale scores, Hoehn and Yahr stage of disease, and computerized measures of motor performance improved significantly with cabergoline treatment. Dose-response effects were not significant. No serious adverse experiences occurred during the 13-week trial, and the side-effect profile mirrored other dopaminergic agonists. Cabergoline appears to be a promising agent in the treatment of Parkinson's disease. PMID- 8451011 TI - Neuromuscular manifestations of Wegener's granulomatosis: a case report. PMID- 8451012 TI - Nerve root enhancement with MRI in inflammatory demyelinating polyradiculoneuropathy. PMID- 8451013 TI - Erythromelalgia: association with hereditary sensory neuropathy and response to amitriptyline. PMID- 8451014 TI - Visual impairment in patients with neurofibromatosis 2. PMID- 8451015 TI - Spasmodic torticollis occurring during alcohol withdrawal. PMID- 8451016 TI - Practice parameters: lumbar puncture (summary statement). Report of the Quality Standards Subcommittee of the American Academy of Neurology. PMID- 8451017 TI - Coenzyme Q. PMID- 8451018 TI - The gut in PD. PMID- 8451019 TI - Aspartame and seizures. PMID- 8451020 TI - Corticosteroids and optic neuritis. PMID- 8451021 TI - Corticosteroids and optic neuritis. PMID- 8451022 TI - Vitamin E and PD. PMID- 8451023 TI - EEG findings in asymptomatic HIV. PMID- 8451024 TI - [Differences in the symptomatology of paroxysmal supraventricular tachycardias in relation to the different sites of localization of the arrhythmic reentry circuit. Clinical picture, semiologic and genetic aspects]. AB - Transesophageal, electrophysiologic studies were conducted in 47 patients, with clinical and ECGgraphic diagnosis of paroxysmal reciprocating supraventricular tachycardia. After admission to hospital, the patients were enrolled in the study in accordance with the criterion concerning the exclusion of patients with signs and symptoms of severe heart pump failure (ie, NYHA III and IV class were excluded). The transesophageal study was performed during paroxysmal tachycardia in each patient to measure the V-A interval and to localize the site of reentry. Thereby, the patients could be grouped into 2 subsets, ie those with A-V nodal reentrant tachycardia (no. 30 patients) and those with accessory pathway reentrant tachycardia (no. 17 patients). Moreover, the prevalence in both subsets was evaluated in the following signs and symptoms: palpitations, dyspnoea, chest pain, pulsations in the neck, significant increase in urinary output, hypotension, dizziness, near-syncope, syncope, shock, focal brain injury. From the data analysis, significantly greater prevalence of palpitations in the neck resulted in the subset of patients with reentry confined to the A-V node (no. 20 cases) compared with those suffering from reentry via accessory pathway (no. 4 cases). Moreover the arterial pressure, in A-V nodal reentrant tachycardia, showed the lowest values and the best decreases, together with the finding of a more rapid trend to decline in comparison with the accessory pathway subset. On the other hand, no significant differences could be seen about the remaining symptoms. In an attempt to provide the reliable explanation for the differences found between the 2 subsets of study, concerning both the unpleasant pulsations in the neck and the pressure decrease, we postulated a remarkable role for the length of arrhythmic circle movement. The smaller dimensions of circuit limbs, in A-V nodal reentrant tachycardia, are likely to be the principle cause of the different clinical features of 2 types of reentry. We speculate actually that in susceptible patients the critical event is most likely to be A-V functional dissociation due to early and unphysiologic activation of atria by stimulus rapidly reentrant from the bottom portion of the AV node: the simultaneous occurrence, frequent in A-V node reentry, of both, atrial and ventricular mechanical activation, would result, however, in impairment of atrial haemodynamics due to development of cannon A waves, able either to activate a vasodepressor reflex from the atria or to stimulate instantaneous release of atrial natriuretic factor in the circulation. Further studies, however, are necessary to be performed on large cases-records, to confirm our hypothesis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8451025 TI - [Duplex scanner diagnosis of complete extracranial carotid artery obstruction: possibilities and limitations]. AB - The authors enhance the current importance of the hemodynamic evaluation of the vascular carotid territory by means of Doppler-CV although the great development of the "real time" ultra sonographic imaging. Combined US/Doppler-CV technique is really useful in differential diagnosis of the severe obstructive disease of extracranial carotid arteries. The authors report the possibilities of pitfalls in diagnosis due to the limitation of devices employed or to the frequent anatomical variability featured by examination of severe obstruction of vascular carotid territory. PMID- 8451026 TI - [Predictive value of the echo-Doppler test in relation to the development of carotid arteriosclerotic plaques]. AB - The authors report their experience relative to 102 patients evaluated with carotid duplex-scanner. Ultrasonographic data of atherosclerotic carotid changes have been correlated with the outcome of the tested series. In fact, echographic images of vascular changes with high thromboembolic risk (ulcerated plaque) have been associated with cerebrovascular injuries in 25% of the cases. Furthermore, the duplex-scanner showed the need for surgical treatment (TEA) in 32 patients with asymptomatic carotid stenosis. Therefore, this noninvasive diagnostic tool seems to play an essential role in the prevention of cerebrovascular ischemia. PMID- 8451027 TI - [Major interventions in vascular surgery with and without autotransfusion. Comparison of coagulation and hemodynamic parameters]. AB - Twenty out of 32 patients undergoing major vascular surgery received autologous blood transfusion and hemostatic and hematological parameters were evaluated in both transfused and non-transfused groups. Blood and urine samples were also analysed. No acceleration of the hemostatic process was observed during either surgery or the postoperative period; free hemoglobin present in reinfusion sacks (?), even in high doses, was immediately restored to normal values in the patient's circulation. A slight effect was observed at the renal level alone. These findings confirm the good qualitative level of the procedures used to reinfuse blood lost during surgery. PMID- 8451028 TI - [The treadmill test in the clinical evaluation of the lower limbs. With special reference to an elderly population group]. AB - The authors show that the treadmill is a good method for studying the peripheral circulation of the inferior limbs, without altering the coronary district capacity. This technique is fitter than the test of Master and/or cycloergometry because it swits the characteristics of elderly patients. The estimate of the vascular function has been carried out by the means of the Winsor Index (WI), which is based on the proportion between the values of the occluding arterial pressure of the posterior tibial in comparison with the humeral arterial pressure. This quotient is able to discriminate the real peripheral vascular insufficiency from the borderline cases as well as from the normal ones, even if not in the presence of painful pathology. We have examined 50 patients; in this group 17 subjects (34%) resulted affected by peripheral arteriopathy of the inferior limbs; 8 of them presented a bilateral form with a pathologic WI; 2 patients of the same above mentioned group resulted symptomatic for pain. The remaining 9 presented a unilateral arteriopathy; of these patients, 6 resulted symptomatic for pains and 3 of them had an already pathologic WI before the stress test. On the contrary, no patients visualized signs of coronary disease; the superficial ECG suffered no alteration; the cardiac frequency has in total increased by 5.8 heart rate. PMID- 8451029 TI - [Reconstructive surgery of the abdominal aorta in a case of left-positioned inferior vena cava. Clinical case and review of the literature]. AB - An unsuspected left-sided inferior vena cava (IVC) can present a formidable challenge for the surgeon attempting abdominal aortic surgery. The incidence of congenital anomalies of the post-renal (infrarenal) vena cava is approximately 3%, with double inferior vena cava most frequently occurring. The authors refer to a case of isolated left-sided vena cava in a 53 year old man who underwent an aorto-femoral bypass graft for aorto-iliac occlusive disease. On the basis of a literature review the authors recall the incidence and the embryology of this anomaly, and analyze its surgical implications, with particular reference to abdominal aortic surgery. PMID- 8451030 TI - [Dissolution of a right cardiac migrant thromboembolus in pulmonary embolism after treatment with rt-PA. Report of a successfully treated case]. AB - We report the clinical, echocardiographic and therapeutic aspect of one case of right cardiac migrant thromboembolus in pulmonary embolism. Medical therapy consisted of tissue plasminogen activator (rt-PA, 100 mg/3h). Progressive reduction of thromboembolus until its disappearance was observed by echo 2D after this therapy. Ec 2D may be an important test in diagnosing pulmonary embolism when perfusion lung scans (extremely sensitive but non specific test) or pulmonary angiography (the most accurate test) are not available at hospital and patient cannot be transferred for his critical illness. PMID- 8451031 TI - Muscarine, oxazole, imidazole, thiazole, and peptide alkaloids and other miscellaneous alkaloids. PMID- 8451032 TI - Microbial pyran-2-ones and dihydropyran-2-ones. PMID- 8451033 TI - Antitumor-promoting activity of scopadulcic acid B, isolated from the medicinal plant Scoparia dulcis L. AB - Scopadulcic acid B (SDB), a tetracyclic diterpenoid isolated from a medicinal plant, Scoparia dulcis L., inhibited the effects of tumor promoter 12-O tetradecanoylphorbol-13-acetate (TPA) in vitro and in vivo; SDB inhibited TPA enhanced phospholipid synthesis in cultured cells, and also suppressed the promoting effect of TPA on skin tumor formation in mice initiated with 7,12 dimethylbenz[a]anthracene. The potency of SDB proved to be stronger than that of other natural antitumor-promoting terpenoids, such as glycyrrhetinic acid. PMID- 8451034 TI - Prognostic value of nucleolar organizer regions in endoscopically biopsied tissues of colorectal cancers. AB - We studied the proliferative activity in endoscopically biopsied tumors by means of argyrophil-protein nucleolar organizer region (AgNOR) scores. AgNOR scores of 109 colorectal cancers ranged from 2.48 to 6.72 (mean: 3.27 +/- 0.52). The 109 tumors were divided into two groups by the median value of AgNOR counts. There was no significant correlation between the AgNOR scores and the histologic type, invasion of bowel wall, lymph node metastases or peritoneal metastases. There was a significant association between the AgNOR scores and lymphatic invasion or liver metastases. Patients with higher AgNOR score tumors had significantly poorer prognoses than those with lower AgNOR score tumors. In Dukes' stage C, especially, the survival rate for patients with higher AgNOR score tumors was significantly lower than for those with lower AgNOR score tumors. Recurrence was found in 8.7% of the tumors with lower AgNOR scores and 19.4% of the tumors with higher scores. Aneuploid tumors had higher AgNOR scores than tumors with the diploid pattern. The results suggest that the AgNOR scores may possibly be a useful prognostic marker of colorectal cancer. PMID- 8451035 TI - Immunohistochemical analysis of estrogen receptors in 313 paraffin section cases of human thyroid tissue. AB - Three hundred and thirteen cases of human thyroid tissues, comprising 39 nodular goiters from 34 females and 5 males, 130 adenomas from 93 females and 37 males, and 144 carcinomas from 99 females and 45 males were used for the present immunohistochemical assessment of estrogen receptor (ER) expression. Thirty-three cases of follicular carcinoma, 115 cases of papillary carcinoma and 6 cases of anaplastic carcinoma were included in the malignant tumor group. Incidences of ER positive cases were 23/39 (58.9%) for nodular goiter, 44/130 (33.8%) for adenoma and 26/144 (18.0%) for cancer. In the individual carcinoma categories, 7/23 (30.4%) follicular, 19/115 (16.5%) papillary and 0/6 (0%) anaplastic lesions were judged as positive cases. Thus, the incidence of ER-positive cases tended to decrease with the degree of malignancy; this trend being similar in both sexes. Moreover, the average ages of ER-positive cases were lower than those of ER negative cases for all types of thyroid carcinoma except the follicular variety in males. It was thus suggested that ER expression may be related to prognosis and tumor growth at early stage. Since the incidence of ER does not significantly differ between females and males, the observed sex differences regarding thyroid tumor incidence may reflect the higher estrogen serum content in females. PMID- 8451036 TI - Bisbenzylisoquinoline alkaloids inhibit tumor promotion by 12-O tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin. AB - Bisbenzylisoquinoline alkaloids, cepharanthine, berbamine and isotetrandrine, were isolated from Stephania cepharantha Hayata. These compounds inhibit arachidonic acid-induced inflammation in mice. We have found that cepharanthine inhibits tumor promotion after topical application and oral administration in two stage carcinogenesis in mouse skin. Furthermore, topical application of berbamine (2 mumol/mouse) and isotetrandrine (2 mumol/mouse) markedly suppressed the tumor promoting effect of 12-O-tetradecanoylphorbol-13-acetate (1 microgram) in mouse skin initiated with 7,12-dimethylbenz[a]anthracene (50 micrograms), at a grade corresponding to that of cepharanthine. PMID- 8451037 TI - Tumor kinetics and timing of the second dose to improve tumor radiocurability--a prediction of the best timing for fractionation by measuring 125I iododeoxyuridine uptake in situ. AB - Experimental radiotherapy using two fractions of X-rays was carried out to study the best time of the second dose to improve the radiocurability of squamous cell carcinoma in WHT/Ht strain mice. Second doses of 27 Gy were given at 0, 6, 12, 24, 60 and 100 h after the first irradiation of 10 Gy. Each time interval relates to a specific change in tumor cell kinetics after irradiation of 10 Gy, that is, completion of PLD and SLD repair, most depression of 125I-IUdR uptake, beginning of increase of clonogenic cells, maximum cell loss rate and bottom regrowth curve, for 6, 12, 24, 60 and 100 h respectively. The local tumor control rates were 100, 78.1 and 96.8% for 0, 6 and 12 h respectively, and then control rates gradually decreased as interval times got longer. A second time window of local control was found 12 h after the first irradiation. This time corresponded to minimal uptake of 125I-IUdR, implying a decrease of S stage cells and depressed DNA synthesis, as suggested from labeling index and grain count studies. Twelve hours may be also the time when cells accumulate at the G2 stage (G2 block) or just after release of the G2 block from the kinetic viewpoint. The 125I-IUdR uptake method may be useful in determining the best time interval for fractionation in situ. PMID- 8451038 TI - Osseous and intestinal compartments in the humoral hypercalcemia of malignancy associated to Walker 256 tumor in rats. AB - The objective of the present work has been to study some aspects of bone and intestinal compartments in rats with Walker 256 carcinosarcoma, an experimental model of humoral hypercalcemia of malignancy (HHM). The results have been compared to those obtained in control animals and, also, to those obtained in Yoshida sarcoma-bearing rats, which were used as tumoral controls without hypercalcemia. Urinary hydroxyproline/creatinine ratio (OHProl/creat) is increased, in both Walker 256 and Yoshida tumor-bearing animals, showing the nonspecifity of this bone marker. However, serum tartrate-resistant acid phosphatase (TRAP) levels are increased in Walker 256 tumor-bearing animals, but they are normal in Yoshida tumor-bearing animals, indicating that TRAP is a better index of bone resorption than OHProl/creat in the HHM syndrome. The decrease of bone calcium content in Walker 256 tumor-bearing rats, not shown by Yoshida-bearing rats, also reflects an increased bone resorption due to HHM. Serum and bone osteocalcin levels are similar in control, Walker 256 and Yoshida tumor-bearing rats, but we observed a decrease in serum alkaline phosphatase levels in Walker 256 and Yoshida tumor-bearing animals, which could also be a nonspecific tumor effect, due to the presence of the neoplasia. Our results support the convenience of the employment of a nonhypercalcemic tumor group as control in the HHM study, in addition to the healthy controls. We have also observed higher 1,25-dihydroxyvitamin D serum levels in Walker 256 tumor-bearing rats than in control and Yoshida tumor-bearing rats. On the other hand, we have found normal levels in the fractional rate of intestinal calcium absorption in Walker-256 tumor-bearing rats, in spite of their high calcium levels, and a significant decrease of this parameter in Yoshida sarcoma-bearing animals. These results support the concomitant contribution of intestinal compartment to hypercalcemia, in the experimental model of HHM studied. PMID- 8451039 TI - LH-RH analogue treatment in adenocarcinoma of the pancreas: a phase II study. Gruppo Ligure per lo Studio del Pancreas. AB - In this phase II study, we treated 7 patients, all males, with stage III or IV pancreatic cancer with goserelin (an LH-RH analogue). Goserelin was administered at a dose of 3.6 mg every 4 weeks. The tumour response was assessed by measuring lesions with US- or CT-scan studies, according to WHO criteria. No response was observed. The median survival was 8 months in locally unresectable tumours and 4 months in advanced disease. The accrual was actually stopped at 7 cases because there were no responses in either of our series or in those published during our study. The authors conclude that the treatment with LH-RH analogue alone cannot be recommended for further studies. PMID- 8451040 TI - Oral medium-dosed metoclopramide versus placebo as highly effective antiemetic prophylaxis in in- and outpatients on noncisplatin chemotherapy. AB - The antiemetic effect of oral medium-dosed metoclopramide (MCL, 3.5 mg/kg b.w./cycle) and placebo for chemotherapy-induced emesis of a noncisplatin regimen was assessed for inpatients and outpatients in two double-blind placebo controlled sequential analyses according to Bross (1952). MCL was given in 5 single doses of 0.7 mg/kg b.w. at 0 h (loading) and at 2 h (i.e. start of chemotherapy) and 6, 10 and 14 h (as maintenance doses). Both studies ended after 8 sequential pairs in favor of MCL (2 alpha = 2 beta = 0.05). Major antiemetic protection (< 2 emetic episodes per 26 h) was achieved for 8/8 of inpatients and 7/8 of outpatients (placebo 0/8 and 0/8). Side effects neither required discontinuation of the antiemetic regimen nor additional therapy. The median of MCL plasma levels ranged from 150 to 750 ng/ml and terminal half-lives from 3.9 to 8.9 h. PMID- 8451041 TI - Phase II study of high-dose ifosfamide as a single agent and in combination with cisplatin in the treatment of advanced and/or recurrent squamous cell carcinoma of head and neck. AB - 152 patients with histologically proven squamous cell carcinoma of the head and neck (advanced and/or recurrent) were treated with a single drug therapy of ifosfamide 1.5 g/m2 by intravenous drip for half an hour in 125 ml of dextrose saline for 5 days and mesna 20% of the total ifosfamide dose in 3 doses for 5 days, or in combination with cisplatin 10 mg/m2 by intravenous infusion for 5 days following the ifosfamide drip. The courses of treatment were repeated at the interval of every 4 weeks, and a total of 3 cycles was given. Out of 152 patients 64 received ifosfamide alone, and 88 received ifosfamide with cisplatin. 6 complete and 25 partial remissions (total response 53%) were observed in 58 evaluable patients of the ifosfamide group, and 10 complete and 40 partial remissions (total response 65.7%) were observed in 76 evaluable patients of the combination group. Nausea, vomiting, alopecia and leucopenia were experienced by all patients. PMID- 8451042 TI - A cisplatinum-cyclophosphamide regimen in advanced ovarian cancer: reporting 5 year results. AB - The following paper reports the evaluation of 53 consecutive patients with advanced ovarian epithelial carcinoma (FIGO stage III-IV), treated between October 1984 and December 1987 with immediate or delayed cytoreduction surgery and chemotherapy. Combination chemotherapy consisted of cisplatinum 45 mg/m2 i.v. for 2 consecutive days and cyclophosphamide 900 mg/m2 i.v. on the second day, administered every 28 days for a maximum of 8 courses. Objective responses were observed in 35 of 50 evaluable patients (70%), 17 (34%) of whom were pathological complete remissions (pCR). For patients with minimal residual disease before chemotherapy a higher pCR rate was achieved (10/20 vs. 7/30; p = N.S.). Median survival time of all patients was 29 months; subjects with minimal residual disease and good performance status before treatment had higher survival (48 vs. 22 months-p < 0.05 and 29 vs. 9 months-p < 0.05, respectively). Median time to progression was 25 months. After a median follow-up of 60 months, 15 (28%) patients were alive, 14 of whom disease-free. Toxicity was moderate with a particularly low incidence of nephrotoxicity and no case of serious long-lasting neuropathy. These findings suggest that the described combination has an efficacy comparable to other CDDP-containing combinations, using 2, 3 or more drugs, with a low incidence of acute serious toxicities and of disabling delayed sequelae. PMID- 8451043 TI - [The painful wrist joint]. PMID- 8451044 TI - [Magnetic resonance imaging. Differentiation with other diagnostic procedures used thus far in examination of the wrist, such as arthrography and scintigraphy]. AB - MRI can be regarded as a standard procedure for diagnosis of the painful wrist. Because of its high costs, it must be used with discretion. For the detection of lesions of the marrow, joint effusions and soft tissue pathology (exception for ruptured ligaments), MRI is generally the most sensitive imaging modality. It shows the living part of bone and soft tissue with unique contrast. An integrative imaging approach including MRI is often successful. X-ray of the wrist is the basic investigation. Ultrasound often allows the diagnosis of pathology of ganglia, tendons and vessels. Lesions of the ligaments are shown best by arthrography, although MRI can also demonstrate these lesions. The introduction of MRI has limited the use of CT to pathologic changes in cortical and cancellous bone and displacement or malalignment. Scintigraphy and MRI are mostly complementary rather than mutually exclusive. PMID- 8451045 TI - [Arthroscopy of the wrist joint]. AB - Our experiences with 100 wrist arthroscopies demonstrate the significance of this technique. In all these cases it was possible to clarify whether one or more pathologies were present or whether the joint was intact. The arthroscope makes it possible to discern the quality and extent of lesion far better than with imaging procedures. Arthroscopy for operations on the wrist seems very promising, but we need much more experience before we can appreciate its full potential and value. PMID- 8451046 TI - [Trispiral tomography and magnetic resonance imaging of the wrist joint]. AB - Tomography and magnetic resonance imaging (MRI) are important imaging techniques in the diagnosis and management of a wide variety of wrist disorders. They have been useful for evaluating fractures, tumors, arthritic conditions and avascular necrosis involving the carpal bones as well as injuries affecting the radiocarpal and intercarpal ligaments and the triangular fibrocartilage complex. The indications and clinical applications of each imaging technique will be discussed. PMID- 8451047 TI - [Dorsal wrist ganglion. Cause of dorsal wrist pain]. AB - Ganglion cysts are the most common soft tissue tumors of the hand. They are more common in women than in men. Although most ganglions can be diagnosed easily on physical examination, ultrasound may be helpful in diagnosing very small (occult) ganglions. Dorsal ganglions typically arise from the dorsal scapholunate intraosseous ligament. Approximately 30 percent of dorsal ganglions resolve spontaneously. For symptomatic ganglia which persist, surgical excision is the most effective treatment. Aspiration and steroid injection appear to be only slightly more effective than no treatment. Recurrence after surgery occurs in roughly 15 percent of cases. PMID- 8451048 TI - [The painful ulno-carpal joint. Diagnosis and therapy]. AB - The ulnocarpal joint plays a critical role in hand and wrist function. It serves as part of forearm rotation as well as part of the carpal kinematics. The joint is comprised of the distal radio-ulnar articulation, triangular fibrocartilage complex, lunate, triquetrum, hamate, and pisiform, and the intra and extracapsular ligamentous and soft tissue constraints. Traumatic disruptions as well as chronic inflammatory conditions are commonplace. In addition to standard radiographs, arthrography, CT scanning, and MRI studies prove useful. Wrist arthroscopy is becoming of increasing importance in this region of the wrist. Ulnar impaction syndrome may occur associated with malunion of distal radius fracture, ulna positive variance, or chronic TFCC tears. Osteotomy of the distal radius or ulnar shortening osteotomy should be considered. Instability of the distal ulna can be treated with tenodesis procedures, hemi-resection arthroplasty, matched ulna resection or the Sauve-Kapandji procedure. PMID- 8451049 TI - [Distal intra-articular radius fractures. Indications for and technique of open reduction and plate osteosynthesis]. AB - In the past few years we have seen vast changes in both the assessment and the management of fractures of the distal radius. This is attributable to several factors. On the one hand, conservative treatment has shown poor results in a considerable number of patients, and on the other hand, more and more young patients are presenting with this common lesion. Furthermore, the spread of new methods of osteosynthesis and of modern materials, such as implants, etc., have greatly improved the results of operative procedures, even in complicated fractures of the radius. Therefore, in certain types of fractures far better functional results can be achieved by open reduction. Particularly in intra articular fractures of the distal radius with or without compression zones and/or injury to the ligaments closed manipulation and subsequent immobilization by plaster is only partially successful. To achieve successful repair of the complex mechanisms in the wrist and the distal radio-ulnar jacket (DRU) joint, these fractures mostly require open reduction and plate fixation including additional support for the articular surface by a cortico-cancellous bone graft from the iliac crest. This enhances the stability of the reduced fragments and facilitates early mobilization which, in turn, greatly improves the functional results. In palmar displaced fractures a palmar approach is employed for both surgical repair and plate fixation, while dorsal compression fractures are reduced, filled and stabilized using a dorsal approach. In this study a special operative procedure for intra-articular comminuted fracture is described. A palmar approach is employed for fracture reduction, while the compression zone is filled by bone graft via an additional dorsal incision.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8451050 TI - [Osteomalacia of the lunate bone--indications for and limitations of radial shortening and ulnar lengthening]. AB - Increased pressure on the lunate bone due to anatomical variance seems to be an important etiological factor in Kienbock's disease. Early diagnosis and treatment may prevent the development of carpal collapse. Ulnar lengthening and radial shortening have proven helpful in stages I-III of Kienbock's disease. PMID- 8451051 TI - [Pseudoarthrosis of the scaphoid bone. Current reconstruction techniques]. AB - Newer reconstruction techniques for scaphoid non-union are directed at the extended objectives of reconstruction of form and length as well as healing of the fracture. The surgical techniques that fulfill these requirements are described with reference to recent literature. PMID- 8451052 TI - [Arthrosis of the wrist joint due to carpal instability. Therapeutic alternatives]. AB - A kinematic analysis of the movement of the scaphoid, the lunatum and the triquetrum has shown that their turning axes do not correspond with each other. Without arthritis, and within the range of normal motion, the bones move without imposing any appreciable load on the ligaments. They merely guide the bones and hold them together. In the case of arthritic disorders and in states where abnormal frictional resistance occurs, or following trauma, the ligaments are highly loaded. This could lead to increased wear and ruptured ligaments. A series of 20 arthroscopies has shown that LT and SC ligaments are very prone to this, and are often affected simultaneously. Therefore, there may be certain predisposed sites or "weak points", which should definitely not be further aggravated by inappropriate therapeutic measures. The clinician can classify the carpal dysfunction into five main groups; however, the therapy options cannot be classified in the same way. On the basis of clinical experience and the kinematic study, the following statements can be made: scapho-lunatum (SC) arthrodesis can be considered kinematically unsuitable, while scapho-capitatum (SC) and lunato capitatum (LC) arthrodeses are both clinically and kinematically acceptable. LC arthrodesis has given good results in cases with advanced carpal collapse. From a mechanical point of view, SC arthrodesis is probably better than scapho-trapezo trapezoid arthrodesis. In the case of ulnar translocation, radio-ulna-to-scaphoid arthrodesis could be an acceptable alternative to total fusion. Proximal row carpectomy can only be a temporary solution, as can prostheses. Partial prostheses, whether of Silastic or titanium, are also not suitable for permanent use.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8451053 TI - [Carpal instability]. AB - Traumatic carpal instability implies that the normal relationships of the radiocarpal and mid carpal joint are distorted either statically or during dynamic stress. Normal kinematics of the carpus are dysfunctional. The causes of carpal instability are dissociation of the intercarpal ligaments on either side of the lunate, a so-called scapholunate dissociation or a luno-triquetral dissociation. Carpal instability nondissociative is generally due to a laxity or attenuation of the intrinsic ligaments of the carpus and are associated with deformity of the distal radius. Ulnar translation of the carpus on the distal radioulnar articular surfaces occurs with shear stretching of the origins of the radiocarpal ligaments. The radial styloid attenuation of the ligaments may result in abnormal motions of the carpal bones going from ulnar to radial deviation at which time a catch-up click may occur. Carpal instabilities are usually associated with malalignment of the lunate with respect to the longitudinal axes of the radius and capitate and tends to assume an extended position with scaphoid fractures or injuries to the scapholunate ligament, a palmar flexed position with injuries to the luno-triquetral area or the ulnar capsule. PMID- 8451054 TI - [Partial arthrodesis of the carpal bones in advanced carpal collapse in chronic scapho-lunar instability and following scaphoid pseudoarthrosis]. AB - Degenerative arthritis of the wrist as a consequence of chronic scapho-lunate instability or chronic scaphoid non-union follows very specific patterns. Joint destruction occurs primarily in the radio-scaphoid and in the luno-capitate joints while the radio-lunar joint is preserved. Treatment by partial carpal fusion between capitate, scaphoid and lunate aims at reconstruction of correct length of the central column and restoration of normal carpal height by reducing the dorsiflexed lunate bone, thereby decompressing the painful radio-scaphoid joint. We have carried out the procedure in 21 cases. At follow up (19 months) 17 patients were free of pain and 4 patients experienced major improvement but had some residual pain. The mean range of motion of the wrist was 57 degrees, representing a loss of 34% of preoperative range of movement. Bony union was achieved in all cases. All patients returned to their former occupation. Partial carpal fusion for treatment of SLAC-wrist and scaphoid nonunion has proven successful with respect to pain relief and partial preservation of wrist motion avoiding complete fusion or arthroplasty of the wrist. PMID- 8451055 TI - [Arthrodesis of the wrist. Indication, technique and functional consequences for the hand and wrist]. AB - Three studies conducted in our center demonstrated an improved technical success rate and elimination of preoperative pain in patients undergoing wrist fusions, with no significant difference in the ability to perform rapid movements requiring manual dexterity in the course of activities of daily living compared with patients who had undergone motion-preserving limited arthrodeses. The only absolute drawback of wrist fusion is that it obviously does not allow for any wrist motion at all. Limited intercarpal arthrodesis preserves some motion, but according to our results never leads to increased motion postoperatively. Several specific skills were found to present difficulty in patients who had undergone total wrist fusion. These included those requiring volar flexion in a limited space, where it would be difficult to have recourse to compensatory motion imparted by the shoulder and elbow, and those requiring forceful pronation and supination with simultaneous strong grasping. For patients involved in certain occupations requiring fine manual dexterity in tight spaces, wrist fusion might not be the most appropriate procedure. It is interesting that there appears to be a learning curve to the patient's ability to undertake specific activities postoperatively. A strong practice effect is present for the first 3-6 postoperative months, during which time a significant improvement in the patient's overall function is noted. Total wrist arthrodesis gives highly predictable results in the treatment of wrist pain and instability. The ability to perform normal activities of daily living and strenuous manual tasks was comparable to that after alternative motion-preserving procedures. We have not observed improved wrist motion after any wrist motion-preserving procedure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8451056 TI - Total shoulder arthroplasty. AB - Shoulder arthroplasty in the modern era was first performed in 1951. Total shoulder arthroplasty (TSA), which includes replacement of the articulating surface of the glenoid, dates to 1973. The intervening 20 years have witnessed multiple prosthetic and surgical approaches. Because the shoulder lacks a true bony socket it relies heavily on the support and integrity of its soft tissue for stability through its extensive range of motion. TSA is a complex and technically demanding procedure. It is however, routinely successful in skilled surgical hands. This article reviews the history of TSA, highlights recent advances and projects future trends and advances. An interdisciplinary Critical Path for short term recovery is presented. Concluding commentary addresses long-term recovery. PMID- 8451057 TI - The effect of structured preoperative teaching on patients' use of patient controlled analgesia (PCA) and their management of pain. AB - This study examined the effect of structured preoperative teaching on patients' understanding of patient-controlled analgesia (PCA) and their management of pain. The experimental group received a written pamphlet and structured preoperative teaching on the use of PCA to manage their pain. The control group received the usual preoperative preparation normally provided by the physician. Both groups were later asked to complete a posttest to determine how well they understood the use of PCA and how well they managed their pain. There was no statistically significant evidence that the experimental group's knowledge of PCA was different from that of the control group. However, there was significant evidence that the experimental group managed their pain better. PMID- 8451058 TI - Methotrexate use in juvenile rheumatoid arthritis. AB - Juvenile Rheumatoid Arthritis (JRA) is a chronic, inflammatory, autoimmune disease of childhood. Methotrexate is an emerging antirheumatic drug in the pediatric population for disease refractory to conventional medications. While observations are encouraging, the toxic side effects can be potentially serious. Toxicity includes gastrointestinal intolerance, ulcerative stomatitis, chemical hepatitis, minor liver fibrosis, infection, hematologic suppression, acute pneumonitis, reversible oligospermia, and cirrhosis. The liver toxicities are of the greatest concern. If proper dosage and monitoring are followed, serious toxic effects can be prevented from occurring. PMID- 8451059 TI - Physical abuse as cause of injury in women: information for orthopaedic nurses. AB - With the frequency and severity of violence against women, it is critically important to empower nurses and physicians with information on physical abuse as a cause of injury in women. The specific aim of this descriptive study was to determine if the cause of injury was from abuse in women presenting to the Emergency Department (ED) with injuries. This research describes the nature and mechanisms of injury by women who reported that their injury was from physical abuse by men. Recognizing domestic violence as a cause of injury and gaining an awareness of the type and mechanism of injury resulting from abuse will help empower orthopaedic nurses to be active in the prevention and treatment of domestic violence against women. PMID- 8451060 TI - Directions: where do we go from here? PMID- 8451061 TI - Acetabular fracture: ORIF. AB - Acetabular fractures are often associated with multiple life-threatening injuries. The initial assessment of the patient sets baseline data for all further nursing assessments. Optimal patient care requires that the nursing staff be knowledgeable about the anatomy of the acetabulum, the classification of fracture type, the influence of the mechanism of injury, and potential complications. A basic understanding of the surgical approach and relevant post operative care is mandatory. Patients with acetabular fractures present a complex nursing challenge. Although nursing involvement may be limited to initial assessment and stabilization prior to transport to a different hospital, a knowledgeable nurse can make a difference in patient outcome. PMID- 8451062 TI - Computerized documentation systems: blessings or curse? AB - This article considers the possibility that computerized documentation systems will negatively impact knowledge development in nursing. Ideas from three vantage points is presented. First, systems are being developed from theoretical frameworks that are not necessarily grounded in nursing, and these systems, in turn, influence the nurses's ability to process and conceptualize information. Second, computer systems may support the retrieval of empirical data to the elimination of other types of data necessary to the development of nursing knowledge. Third, computers may decrease opportunities for collegial dialogue. These factors together create an atmosphere of "technologic determinism" (Robinson & Robinson, 1990), which can inhibit the development of new ideas in nursing. PMID- 8451063 TI - The radiographic appearance of gout. AB - Gout is a disease that often leads to gouty arthritis, an arthropathy caused by elevated serum uric acid. Bony changes are not usually seen until years after the first clinical symptoms. This article describes gout and gouty arthritis with special reference to radiographic changes associated with the disease. PMID- 8451064 TI - NAON's GRC is developing a bloodborne pathogen position statement. PMID- 8451065 TI - Licensure of advanced practice nursing: what's our position? PMID- 8451066 TI - On becoming a specialist. PMID- 8451067 TI - Specialization. PMID- 8451068 TI - 32 health care workers got HIV while on the job. PMID- 8451069 TI - The role of type IX collagen in osteoarthritis and rheumatoid arthritis. AB - Articular cartilage consists of a cellular and an extracellular compartment. The extracellular compartment is composed of collagen, proteoglycans, and noncollagenous matrix proteins. Collagen resists tensile forces and serves as an organizing skeleton that helps maintain the structural integrity of cartilage. Fourteen types of collagen have been identified. The cartilage-specific collagens are type II (the principal component), type IX, type X, and type XI. Type IX collagen is hypothesized to be the "glue" that holds together the type II collagen latticework of articular cartilage. Degradation of type IX collagen by proteolytic enzymes has been observed in the primary stages of osteoarthritis and rheumatoid arthritis. This degradation is thought to represent an "ungluing" of the collagen scaffold and has been proposed as the mechanism for the degenerative changes seen in osteoarthritic and rheumatoid cartilage. PMID- 8451070 TI - Pathophysiology and mechanisms of compartment syndrome. AB - Compartment syndrome is a serious potential complication of trauma to the extremities. Increases in intracompartmental tissue pressure result from increases in fluid pressure plus the contributions of cells, fibers, gels, and matrices. The result is an increased venous pressure that lowers the arteriovenous pressure gradient, resulting in decreased local blood flow. While fasciotomy is the definitive treatment for an established compartment syndrome, preventive measures can be taken early to modify or halt the process. Tissue pressures are helpful in monitoring or establishing the diagnosis. However, their use requires a clear understanding of the pathophysiology of compartment syndrome for proper clinical correlation. Recent studies have suggested that determination of the difference between the mean arterial and compartmental pressures (delta P) is more useful than the absolute tissue-pressure measurement. This article reviews the pathophysiology and mechanisms of compartment syndrome. PMID- 8451071 TI - Vascularized bone autografts. AB - Recent advances in microvascular surgery have made it possible to reconstruct large skeletal defects with autogenous bone grafts on a vascular pedicle. Experimental studies have demonstrated that vascularized bone grafts have superior blood flow and osteocyte survival when compared with nonvascular grafts. This improves the union rate and allows full incorporation of cortical bone, remodeling, and graft hypertrophy. Clinical experience over the past decade demonstrates that 80% to 90% of these grafts are ultimately successful, allowing limb salvage in complex reconstructive cases. However, the technique is technically demanding, has a relatively high complication rate, and requires prolonged immobilization and rehabilitation. Thus, vascularized bone grafts should only be used when simpler reconstructive techniques are unlikely to succeed. PMID- 8451072 TI - Legg-Perthes disease in children under 6 years old. AB - A roentgenographic review was made of 109 patients with unilateral Legg-Perthes disease, all of whom had experienced onset of symptoms prior to their sixth birthday. Roentgenograms taken at the time of healing and at final follow-up were grouped according to Catterall classification and modified Mose rating. The parameters measured were epiphyseal index, center-edge angle, extrusion index, epiphyseal quotient, and center-edge quotient. Average age at final follow-up was 12 years. A change in Mose rating between assessments at healing and final follow up occurred in 16% of patients, with most of them showing improvement, supporting the concept that femoral heads in young children have the capacity to remodel. However, 24% of patients with Catterall III and IV disease had a poor result at final follow-up. Despite early onset of Legg-Perthes disease, patients with involvement of greater than half the femoral head are at risk for poor roentgenographic result. PMID- 8451073 TI - Treating tibial fractures with a modified Sarmiento method. AB - There is still no unanimous agreement on the appropriate primary treatment of tibial fractures. One fraction advocates conservative treatment, and another advocates open reduction and internal fixation. Between these extremes is the functional treatment developed by Augusto Sarmiento. The authors adopted Sarmiento's method in 1976 and present a prospective study of 317 cases treated between 1976 and 1988 in which the union rate was 98.7%. They describe the Sarmiento method as ideal for closed, spiroid (whether comminuted or not) tibial fractures resulting from low-energy forces. PMID- 8451074 TI - Chronic recurrent multifocal osteomyelitis. AB - Chronic recurrent multifocal osteomyelitis is a rare entity that is easily confused with pyogenic osteomyelitis. Three cases that illustrate the common modes of presentation and roentgenographic findings are presented. The current orthopaedic literature is reviewed, and management guidelines are discussed. PMID- 8451075 TI - Congenital kyphosis. AB - Congenital kyphosis is a rare spinal deformity, and many physicians are unfamiliar with its proper treatment. Following a case report, this article presents a brief synopsis of the literature. We present the case history of a 45 year-old woman with a congenital kyphosis of 140 degrees who has been followed at our institution for 39 years. No treatment was ever prescribed, affording the unique opportunity to study the natural history of this entity in a particular patient. PMID- 8451076 TI - A 2-year-old girl with painful right ankle. AB - The following case is presented to illustrate the roentgenographic and clinical findings of a condition of interest to the orthopaedic surgeon. The initial history, physical findings, and roentgenographic examinations are found on this page. The final clinical and roentgenographic differential diagnosis is then presented. PMID- 8451077 TI - A new method for reduction of hip dislocations. AB - Traumatic hip dislocations and dislocation of total hip arthroplasties are common injuries. Closed reduction of either a dislocated hip or a total hip arthroplasty can be a demanding procedure and may necessitate open reduction if unsuccessful or lead to further complications. These include fracture or neurovascular injury to the patient, as well as injury to the surgeon when reducing the hip. This article describes a technique that reliably reduces dislocations while minimizing complications. PMID- 8451078 TI - High tibial osteotomy: fixation with cannulated screws. AB - There have been many modifications of the proximal tibial osteotomy since it was initially described by Jackson in 1958. The trend toward rigid internal fixation and early motion after osteotomy prompted the authors to develop a technique using cannulated screws for stabilization. This method is simple and quick, involves no soft-tissue dissection, and allows early postoperative motion. PMID- 8451079 TI - Historical perspectives of neonatal transport. AB - A personalized view of the growth and development of neonatal transport is presented. The public display of premature infants in France and Germany and the beginning of the transport incubators in Chicago are explained. How the policy of regionalization was developed and diluted during the readjustment phase is discussed. PMID- 8451080 TI - The organization of a pediatric critical care transport program. AB - Highly specialized pediatric critical care centers have matured significantly over the past two decades; however, access to this care is limited to tertiary care facilities and constrained by geography. With the advances of transport medicine, great distances can be spanned to bring critical care to the patient and provide effective treatment and safe transport systems where specialized care was previously unavailable. A patchwork of diverse transport systems perform pediatric transports with significant differences in the level of pediatric critical care. The optimal transport system has yet to be fully defined, but many successful systems share fundamental elements of organization. PMID- 8451081 TI - Intra-transport stabilization and management of the pediatric patient. AB - During the period of interhospital transfer, a critically ill child is at risk from the disease, the therapy, and the transfer itself. This risk can be minimized by good communication between the referring and receiving caretakers, careful evaluation and management, anticipation of complications, and a well equipped and well-trained transport team providing a level of care as close as possible to that available at the receiving critical care unit. PMID- 8451082 TI - Neonatal transport. Outreach educational program. AB - Neonatal transport is an integral part of a regionalized system of perinatal health care delivery. An effective outreach educational program promotes early identification of high-risk neonates, consultation, communication, and referral. The education offered in several formats also promotes optimal pretransport and intratransport stabilization of referred neonates. This improved stabilization may favorably influence the overall neonatal outcome. The impact of education in the region can be determined by a systematic review of referral patterns, standard of care during stabilization, and neonatal outcome. An organized outreach educational effort is therefore an essential aspect of any neonatal transport program. PMID- 8451084 TI - Evaluation, treatment, and transport of pediatric patients with shock. AB - Early recognition and correct treatment of shock remain the most important keys to preventing the death and disability frequently caused by this condition in children. The pediatrician plays a vital role in this process and in referral of the patient for transport to tertiary care centers, where shock is best managed. The transport environment creates special challenges in initial stabilization and ongoing treatment of shock. Discussion centers on clinical clues to recognition, on simple measures available to increase tissue oxygenation, and on the issues of pretransport and transport treatment. Support of airway and breathing, vascular access, and correct fluid therapy remain the cornerstones of successful treatment. PMID- 8451083 TI - Cardiopulmonary resuscitation of newborns. Its application to transport medicine. AB - The outcome of sick infants requiring transport to tertiary care centers is critically dependent on the stabilization of these infants at the hospital of delivery and the quality of care during transport. The American Heart Association/American Academy of Pediatrics guidelines for neonatal resuscitation emphasize a structured, step-wise approach to resuscitation. This article highlights the application of these guidelines to resuscitation of newborns during transport and reviews the experience of a large perinatal network in this area. PMID- 8451085 TI - Drowning and near-drowning. AB - The incidence, epidemiology, and pathophysiology of drowning and near-drowning are presented. Particular attention is paid to the neurologic and pulmonary pathophysiology indicators for monitoring and laboratory tests. Special attention to transportation of patients is given, and treatment in the field, emergency department, and pediatric intensive care unit is delineated. PMID- 8451086 TI - Transporting the neurologically compromised child. AB - The initial evaluation, stabilization, and subsequent transport of the neurologically compromised child should take into account the pathophysiologic response of the CNS to a variety of injurious factors. Little can be done to avoid neuronal damage from the primary event. Secondary insults resulting from hypoxemia, ischemia, intracranial hypertension, and fluid shifts can and must be prevented to ensure maximum neuronal salvage, however. Maintenance of an adequate airway, breathing, and circulation assume an immediate and ongoing priority. Neuroresuscitation should be directed toward reversing alterations in cerebral metabolism, autoregulation, brain water, and ICP associated with individual pathologic states. PMID- 8451087 TI - Transport and stabilization of the pediatric trauma patient. AB - The incidence of pediatric trauma continues to increase, presenting at almost every emergency department. Life-threatening injuries need to be cared for immediately, in whatever institution the patient presents. For severely injured children, optimal care is ultimately provided at specialized trauma centers. Physicians caring for trauma patients in less specialized institutions must be aware of who to transfer to a trauma center. Effective stabilization and timely, safe transport are vital to reduce further injury. PMID- 8451088 TI - Airway management and sedation for pediatric transport. AB - Appropriate airway management is essential for the successful transport of sick children. Airway management begins with a thorough history and physical examination and may proceed to invasive therapeutic interventions. Successful care of the pediatric airway can be achieved only with a thorough knowledge of airway management technique and equipment. In addition, familiarity and understanding of the pharmacologic adjuvants to airway management and sedation will help to achieve the primary objective of any transport team, namely a safe and smooth transport of the critically ill child. PMID- 8451089 TI - Transport management of the patient with acute poisoning. AB - Poisoning in children is a common clinical problem encountered by pediatricians, general practitioners, and emergency room physicians. Poisoning in children less than 5 years of age is usually accidental, whereas, in young adults, any disparity between expected history and clinical findings should suggest poisoning. It is imperative that the treating physician expeditiously recognize, begin treating, and plan to transfer, when indicated, by specialized pediatric transport team the critically ill poisoned child to a tertiary care facility. PMID- 8451090 TI - Assessing adherence to standards for neonatal resuscitation taught throughout the perinatal referral area. A quality assurance activity. AB - The American Heart Association/American Academy of Pediatrics Neonatal Resuscitation Program provides standards for management of newborn infants in birthing areas. Certification and subsequent evaluation of birthing area personnel at perinatal network hospitals should result in better stabilization of infants prior to transport. PMID- 8451091 TI - Air transport. AB - Air transport has become an integral element of pediatric transport programs. The use of both fixed-wing (airplane) and rotorwing (helicopter) aircraft has increased. Appropriate vehicles configured for the safe and effective transfer of pediatric and neonatal patients are available. As the acuity of patients requiring air transport has increased, more sophisticated and specialized training in the areas of flight physiology and transport medicine is required. The limitations of air transport and air transport vehicles must be understood to assure that the optimal modality is selected for a specific transport. PMID- 8451092 TI - Febrile children with no focus of infection: a survey of their management by primary care physicians. AB - We mailed a checklist survey to 1600 randomly selected pediatricians, family practice physicians (FPPs) and emergency medicine physicians (EMPs) in the United States regarding their management of children with high fever and no focus of infection at various ages: 3 weeks; 7 weeks; 4 months; and 16 months. Completed questionnaires were returned by 211 of 600 (35.2%) pediatricians, 145 of 500 (29%) FPPs and 141 of 500 (28.2%) EMPs. Most pediatricians, FPPs and EMPs would hospitalize a 3- or 7-week-old infant with fever and most pediatricians and FPPs would treat infants of this age group empirically with antibiotics. Most pediatricians, FPPs and EMPs would not hospitalize a 4-month-old or a 16-month old with high fever with no focus of infection but 44 and 25% of pediatricians, 38 and 24% of FPPs and 41 and 34% of EMPs, respectively, would treat a 4- and 16 month-old child with high fever and no focus of infection with antibiotics. The preferred antibiotic treatment for hospitalized 3- and 7-week-old infants was ampicillin plus gentamicin or ampicillin plus cefotaxime; for older outpatients preferred treatment was amoxicillin or ceftriaxone. We conclude that hospitalization and empiric antibiotic treatment of very young infants (< 2 months of age) with high fever and no focus of infection are preferred by most of the pediatricians, FPPs and EMPs surveyed. Nearly one-half of these physicians would treat 4-month-olds and a fourth would treat 16-month-olds with high fever and no focus of infection with antibiotics as outpatients. PMID- 8451093 TI - Length of prediagnostic history related to the course and sequelae of childhood bacterial meningitis. AB - The relationship between length of prediagnostic history and course and sequelae of childhood bacterial meningitis was prospectively examined by collecting data from 286 children with bacteriologically confirmed bacterial meningitis. The cases were divided into three groups: short (< or = 24 hours, N = 141); intermediate (> 24 to 48 hours, N = 75); and long (> 48 hours, N = 70) history. The level of consciousness and serum C-reactive protein normalized sooner during hospitalization in patients with a longer history. They also showed neck stiffness more often and longer and had thrombocytosis earlier and more prominently than patients with a shorter history. The differences were not influenced by etiology, sex or age. The occurrence of neurologic abnormalities in the hospital or during the first 6 months after discharge was not affected by duration of illness before hospitalization. We conclude that our results support the view that bacterial meningitis presents in two forms. At presentation the more acute form often has a history of less than 24 hours and poses a great danger to the patient. In contrast the other form develops insidiously and is more difficult to detect but does not have a worse prognosis than the acute form. PMID- 8451094 TI - Preceding respiratory infection predisposing for primary and secondary invasive Haemophilus influenzae type b disease. AB - Cases (117) with invasive Haemophilus influenzae type b (Hib) disease and their family members reported symptoms of respiratory infection during the 4-week period before the onset of Hib disease significantly more often than age-, sex- and residence-matched controls (225) and their family members during the same time period. Viral (adenovirus; influenza A and B; parainfluenza types 1, 2 and 3; and respiratory syncytial virus) and Mycoplasma pneumoniae serology was performed in 84 paired sera from cases and 112 paired sera from controls, who were healthy children matched to the cases by age, year and season. Viral or M. pneumoniae infection was diagnosed equally often among cases and controls (18% for both groups). However, patients who were associated cases of Hib disease (i.e. either the primary or secondary case of a case pair) had a diagnostic viral serology more often (50%) than did sporadic cases (13%) (odds ratio, 7.0; 95% confidence interval, 1.6 to 33; P = 0.006). These results suggest that some infectious agent(s) caused symptoms among the patients and circulated among the patients' closest contacts immediately before their development of Hib disease and possibly predisposed for invasive Hib disease. For the development of associated Hib disease among close contacts of an index case, adenovirus, influenza A, respiratory syncytial virus or para-influenza type 1, 2 and 3 infections may be important. PMID- 8451095 TI - Dilemmas in diagnosis and management of cephalosporin-resistant Streptococcus pneumoniae meningitis. AB - We recently managed an infant with meningitis caused by Streptococcus pneumoniae in whom ceftriaxone failed to sterilize the cerebrospinal fluid after 6 days of therapy. This strain, which had a penicillin minimal inhibitory concentration (MIC) of 2 micrograms/ml, appeared susceptible to ceftriaxone (MIC < 0.5 micrograms/ml) when evaluated by a commercial MIC panel (Microtech Medical Systems, Inc., Aurora, CO) but was found to have a ceftriaxone MIC of 4 micrograms/ml when evaluated by conventional microtiter broth dilution technique. Furthermore ceftriaxone therapy of meningitis induced with this strain in a rabbit model was ineffective. Thirteen of 112 pneumococcal strains (11.6%) isolated recently at Children's Medical Center of Dallas were penicillin resistant, and 3 of these were highly penicillin-resistant (MIC > or = 2 micrograms/ml). The incidence of pneumococcal strains with cefotaxime MICs > or = 1.0 micrograms/ml has increased from 0 of 258 from 1981 to 1983 to 5 of 112 (4.5%) from 1991 to 1992. The definition of cephalosporin resistance for pneumococci requires modification and further studies of the antibiotic management of meningitis caused by such strains are needed because resistance to cephalosporins is increasing and the extended spectrum cephalosporins may be ineffective as sole therapy. PMID- 8451096 TI - Why diagnose influenza infections in hospitalized pediatric patients? AB - The advent of rapid diagnostic testing for respiratory syncytial virus facilitated decisions for isolation of infectious hospitalized patients. However, diagnosing other viruses by clinical examination such as influenza may be difficult. If patients with influenza are not diagnosed on hospital admission, nosocomial infections may occur. The purpose of our study was to identify patients with nosocomial influenza infections during one winter season in a large children's hospital, document the morbidity, identify potential index cases as roommate exposures who were not identified as having influenza at the time of admission and determine ways in which these cases could have been prevented. From December, 1989, to March, 1990, 74 patients were found to have positive influenza cultures; 11 (15%) were determined to be nosocomial in origin. Hospitalization was extended for 6 patients. Additional costs for these 11 patients resulting from influenza infection totaled +83,000. Six index cases were identified as potential exposures to 7 (67%) of those who acquired nosocomial infections. In none of these potential index cases had influenza been considered as an admission diagnosis. Rapid tests for influenza are necessary to identify patients with influenza at admission and to identify hospitalized patients with nosocomial infection to decrease the number of diagnostic tests and institute appropriate isolation procedures. PMID- 8451097 TI - Historical cohort evaluation of ribavirin efficacy in respiratory syncytial virus infection. AB - Evaluation of ribavirin therapy for respiratory syncytial virus infection of the lower respiratory tract is problematic because of multiple risk factors and variable severity of illness in respiratory syncytial virus-infected patients. To address these difficulties we used multivariate analysis and performed a historical concurrent cohort study in two children's hospitals one of which had used ribavirin since licensing and one that had not utilized ribavirin therapy. The medical records of 158 patients who satisfied the American Academy of Pediatrics inclusion criteria for receiving ribavirin were analyzed for three seasons (1988 to 1991). No significant benefit of ribavirin therapy could be appreciated for the whole group in length of stay (median, 5.0 vs. 6.5 days), days on oxygen therapy (median, 5 vs. 3), progression to ventilator status (3.8 vs. 3.9%) or mortality (1.9% vs. 1.9%) for ribavirin treatment vs. supportive care. Multivariate analysis failed to uncover a beneficial effect of ribavirin when all risk factors were considered. No significant differences were noted when ventilated and nonventilated patients were examined separately. Our data raise questions about the efficacy of ribavirin when used in common practice and suggest that further prospective study, with appropriate analysis, is needed to justify the continued widespread use of this drug. PMID- 8451098 TI - Ribavirin effect on pulmonary function in young infants with respiratory syncytial virus bronchiolitis. AB - To assess the effect of ribavirin on pulmonary function in infants with respiratory syncytial virus bronchiolitis, we performed a randomized (nonmatched), double blinded, placebo-controlled study of 19 infants with RSV bronchiolitis. Infants with underlying respiratory, cardiac or immunologic disease were excluded. Patients were given ribavirin (10) or placebo (9) via an aerosol generator for 18 hours/day for 3 days. Pulmonary function (dynamic compliance, total lung resistance) was calculated using a pneumotachographic method on Days 1, 2 and 7. Differences between groups on clinical criteria were not found. Approximately one-half of each group showed increased compliance and decreased lung resistance after 24 to 48 hours of therapy. By Day 7 compliance had increased 30% in the placebo group and 210% in the ribavirin-treated infants (P = 0.05). Significant differences in the rate of change of lung resistance were not seen by Day 7. We conclude that previously noted improvements in the early course of respiratory syncytial virus bronchiolitis treated with ribavirin do not appear to be a result of measurable changes in pulmonary function. However, paradoxical increases in airway resistance were not found in patients treated with ribavirin. PMID- 8451099 TI - Lack of detectable human immunodeficiency virus infection in antibody-negative children born to human immunodeficiency virus-infected mothers. AB - More than one-half of the children born to women with human immunodeficiency virus (HIV) infection are not infected with HIV. Most of these children, although born antibody-positive, lose maternal antibody and remain asymptomatic. However, it has been unclear how many antibody-negative children of HIV-infected women may truly be infected despite the loss of passively acquired maternal antibody. One hundred nine children who lost maternal antibody after birth to HIV-infected women recruited in four United States maternal HIV transmission studies were examined for HIV infection. Polymerase chain reaction (PCR) was used to determine whether children had HIV proviral DNA in peripheral blood mononuclear cells. A total of 268 samples from 109 children were tested. Clinical status and other laboratory findings were also evaluated. The median age at last follow-up was 25 months (range, 12 to 48 months). One hundred seven (98%) children were negative by PCR on all samples tested. None (95% confidence interval, 0.0 to 1.9%) of 109 children had a repeatedly positive PCR. Two children had single positive PCR results that could not be confirmed on subsequent testing. No other laboratory or clinical findings supported HIV infection in either of these children. The loss of HIV antibody in an asymptomatic child born to an HIV-infected woman strongly suggests that the child is not infected with HIV. Single positive PCR results, particularly in the absence of other clinical or laboratory evidence of HIV infection, should not be used alone to diagnose HIV infection. PMID- 8451100 TI - Vertebral osteomyelitis in children. PMID- 8451101 TI - Fibronectin in host defense: implications in the diagnosis, prophylaxis and therapy of infectious diseases. PMID- 8451102 TI - Pulmonary cryptococcosis presenting as metastases in children with sarcomas. PMID- 8451103 TI - Pneumococcal serotypes causing disease in children in Alabama. PMID- 8451104 TI - Ceftazidime for therapy of children with chronic suppurative otitis media without cholesteatoma. PMID- 8451106 TI - Fatal childhood pneumococcal Waterhouse-Friderichsen syndrome. PMID- 8451105 TI - Transferase values in infants at risk from human immunodeficiency virus type 1 perinatal infection. PMID- 8451107 TI - Bacillus cereus pneumonia in premature neonates: a report of two cases. PMID- 8451108 TI - Neonatal Clostridium sordellii toxic omphalitis. PMID- 8451109 TI - Parotitis in diarrhea-associated hemolytic uremic syndrome. PMID- 8451110 TI - Pseudomonas sepsis in children without previous medical problems. PMID- 8451111 TI - Therapeutic implications of erythromycin resistance in group A streptococci. PMID- 8451112 TI - Preschool children's motor development and self-concept. AB - The relationships among age, motor age, and perceived competence of 31 preschool children were explored. The Peabody Motor Developmental Scales and the Pictorial Scale of Perceived Competence and Social Acceptance assessed children's motor age and perceived competence, respectively. Stepwise regression analyses indicated that age followed by perceived competence contributed significantly to children's motor age. However, neither age nor motor age contributed significantly to perceived competence. PMID- 8451113 TI - Potentially relevant alternative interpretation of infants' addition and subtraction. PMID- 8451114 TI - Spatial coding of information on temporal order in short-term memory. AB - This study examined the effect of spatial cues on judgments of temporal order for digits presented to the right or left visual field. 56 subjects were better able to recall temporal order on trials with congruent temporal and spatial cues, and on trials in which stimuli were presented to the right visual field. The implications of these results for several models of temporal encoding are discussed. PMID- 8451115 TI - Perceptual development and early childhood injuries: a prospective pilot study. AB - A prospective pilot study of 172 Hispanic children was performed to identify developmental predictors of 9 maternal reports of childhood injuries that required medical attention during the following year. The 1972 McCarthy Scales of Children's Abilities was administered near the children's third birthday and maternal reports of injuries were obtained the following year. Multiple regression analysis indicated that the Verbal, Perceptual, Quantitative, Memory, and Motor Subscales of the McCarthy Scales of Children's Abilities accounted for a small but statistically significant proportion of variance. Within the model, children who showed advanced abilities on the Perceptual Subscale were more likely to reported as having an injury requiring medical attention during the subsequent 12-month period. PMID- 8451116 TI - Body-image distortion among male and female American and Costa Rican students and female Japanese students. AB - 395 American male and female high school and college students, 286 Costa Rican male and female high school students, and 127 Japanese female college students were tested for body-image distortion using a computer-based body-image distortion task. A reliable negative relationship between stature and body-image distortion was observed. No reliable differences in body-image distortion were observed between different sex or cultural groups. PMID- 8451117 TI - A study with a follow-up of the effects of music education on holistic development of empathy. AB - Half of the 32 children, aged 6 yr. old, took part in the 12-hr. holistic empathy education program with music exercises over three months. Others were controls. Children were tested at a pretest, 3 months later at the posttet after the training, and follow-up test, 9 months after posttest. The Feshbach and Roe Empathy Slide Test, the Weir and Duveen Prosociability Rating Scale, and the Kalliopuska Prosociability Rating Scale for Teachers were used. Empathy and prosociability increased significantly from pretest to posttest after empathy education. As hypothesized, comparison of pretest and follow-up test results showed a significant increase in empathy for the test group and a nonsignificant increase among controls. PMID- 8451118 TI - Thoughts on perceptual influences of colored paper. AB - Much of the material one reads is in black and white. It is proposed that the color of paper may influence perception and performance on pen-and-paper tasks. PMID- 8451119 TI - Factors affecting perception of outdoor public environments. AB - Comfort and related perceptions are important in respect to use of outdoor public places. In a laboratory, 170 persons viewed four such places on slides and rated them on 10 dimensions, namely, "comfortable," "playful," "serious," "active," "unsafe," "good," "tense," "interesting," "gloomy," and "pleasing." Instructions were used to vary time of day and the number of people present at the location. It was found that women (n = 96) regard outdoor environments as more threatening than do men (n = 74) which suggests that women feel more vulnerable to untoward acts and that public places are rated less desirous at dusk than at dawn, presumably because dusk is followed by night and dawn by day. It was also discovered that such public environments are rated better than deserted places when occupied by two or more persons. Some of these results are consistent with the Prospect-Refuge Theory of Appleton. PMID- 8451120 TI - Body-image dissatisfaction among American male and female college students: a computer-based graphical approach. AB - College students (56 women and 43 men) attending state colleges in the southwestern United States were tested for body-image dissatisfaction using a computer-based graphical body-image task. A reliable relationship between desired stature and desired body-image was observed for the women. Women of large stature showed a greater discrepancy between verbally reported desired stature and redrawn images of desired stature than women of average or smaller than average stature. No reliable discrepancy between desired body-image and verbally reported desired stature was shown by the men. PMID- 8451121 TI - Visual preferences of preschool children for abstract and realistic paintings. AB - 40 children ages 2 or 3 years were asked to express preferences for 9 abstract and 9 realistic paintings on two separate occasions. Children showed no clear preferences and these were stable over occasions. Their drawings were classified in the scribble stage. These results were consistent with downward extensions of aesthetic preference theories. Implications for the usual environments of young children were discussed. PMID- 8451122 TI - Impairment of saccadic eye movements by scopolamine treatment. AB - The effects of Scopolamine on the dynamics of saccadic eye movements, stimulated over a random time interval, have been investigated in humans. A 0.5-mg dose of the drug (intramuscular injection) had various influences on the basic saccadic parameters. For all subjects duration increased and peak velocity decreased, while for 50% of the subjects saccades became hypometric and latency increased. Standard deviation increased consistently too. Moreover, the Scopolamine treatment affected postsaccadic fixation; at the end of many saccades, the eye drifted considerably, but stability was recovered after a few seconds. PMID- 8451123 TI - Shifts in the Plutchik emotion profile indices following three weekly treatments with pulsed vs continuous cerebral magnetic fields. AB - Compared to baseline measures, the emotional profile indices of normal volunteers who received 3 weekly exposures to 20 min. of bilateral burst-firing magnetic fields along the temporal plane displayed increased aggression and decreased trust relative to those exposed to pulsed (1 sec. every 4 sec.) fields or to control conditions. The effect size was equivalent to an eta of 0.70. There were no shifts in Holtzman Inkblot Projection Scores. These results suggest that brief cerebral exposures to weak magnetic fields that simulate the burst-firing of amygdaloid cells may affect specific limbic emotions. PMID- 8451124 TI - Sinistrality and reduced longevity: Reichler's 1979 data on baseball players do not indicate a relationship. AB - Halpern and Coren's 1988 results concerning the longevity of sinistral and dextral baseball players have been used to support the idea that sinistrality is associated with reduced longevity. Halpern and Coren stated that they used Reichler's 1979 The Baseball Encyclopedia, which has longevity data through 1978, as their source. Apparent errors in reporting findings from that source suggested the possible value of analyzing Reichler's 1979 data. That analysis indicated findings that did not confirm Halpern and Coren's 1988 findings. Coren, however, related in 1992 that, although Halpern and Coren used Reichler as their source, they considered longevity data only through 1974. We therefore contend that the present findings represent what Halpern and Coren would have found had they considered Reichler's longevity data through 1978. Procedures used to analyze baseball player's longevity and the possible value of and potential problems with an updated baseball study are discussed. PMID- 8451125 TI - Comparison of cholesterol in habitually high and low active school-age children. AB - While risk-factor screening programs for coronary artery disease have been effective among adults, few programs are available for school-age children. 31 children were screened (16 active and 15 inactive) for cholesterol levels. The physically active group had a nonsignificantly lower mean which may reflect the small sample. PMID- 8451126 TI - Video-task paradigm extended to Saimiri. AB - In the "video-task paradigm" a subject manipulates a joy-stick to move a cursor into an experimenter-defined target area on a computer monitor, generally receiving a food reward upon completion of the task. Despite the spatial separation of the joy-stick, monitor, and location of reward delivery, the video task paradigm has been successfully implemented with several macaque species and with chimpanzees. Preliminary attempts to implement the paradigm with squirrel monkeys, however, were not successful. This report describes successful performance by a squirrel monkey in the paradigm. After learning to move the cursor to contact a small target randomly appearing at four screen locations, the monkey was readily able to move the cursor to contact a moving target in novel locations on the monitor screen. PMID- 8451127 TI - Induced visual motion: effects of fixation and retinal position. AB - In the first of two experiments (N = 33) on the effects on induced motion of target fixation and retinal position, better induced motion was always perceived in a target which was fixated and centered on the fovea than in nonfixated target stimuli which projected onto various locations on the periphery. A similar fixation effect was again observed in Exp. 2 (N = 29) when the nonfixated stimuli fell within the fovea. Ratings of induced motion tended to decrease as retinal eccentricity of the nonfixated stimulus increased in both experiments. The results indicate that target fixation and retinal position should be controlled in research on induced motion. Also, the data may emphasize the similarity of real and induced motion perception. PMID- 8451128 TI - Brief treatment of children's dental pain and anxiety. AB - Pain interferes with children's dental care, but anxiety and pain are often confounded. We tested a classical-conditioning model of dental pain with 45 8- to 11-yr.-old children but found little support for it. Instead, different treatments for pain were effective in reducing the children's expectations of discomfort. Expected discomfort may be the most important part of dental pain, so expectations might well be the focus of such treatments. PMID- 8451129 TI - Age-related decline of psychomotor speed: effects of age, brain health, sex, and education. AB - A cross-sectional study into age-related decline of psychomotor speed is reported. A newly introduced choice response task was used, involving three conditions: simple reaction time (SRT), choice reaction time (CRT), and CRT with stimulus-response incompatibility. Subjects were 247 volunteers, aged 20 to 80 yr. in seven age levels. Although all subjects thought themselves to be normal and healthy, a post hoc division could be made based on biological life events (BLE, mild biological or environmental factors that can hamper optimal brain functioning, such as repeated general anesthesia). Performance was poorer by subjects who had experienced one or more such event: slowing was comparable to the effect of age, especially in the more difficult task conditions. There were significant effects of sex and education, men being consistently faster than women, and more highly educated subjects performing better than subjects with only low or medium education. These findings replicate observations from other test methods. They are also in line with several other studies giving interactions between the effects of aging and physical fitness. This study questions the validity of much research on aging, as the data suggest that a more rigorous health screening for biological life events in subjects recruited from the normal, healthy population can reduce performance effects normally ascribed to aging. PMID- 8451130 TI - Effects of three colors in an office interior on mood and performance. AB - This study examined the effects of three hues on subjects' performance and mood while in an office work environment for 1 hour. Pretest/posttest measurements were completed. Work performance was measured using words typed, typing errors, and a ratio of errors to words typed. Anxiety, depression, and arousal were measured by the Eight State Questionnaire of Curran and Cattell. A total of 45 women, ages 18 to 24 years, were tested individually in a single office space: 15 when the office walls were painted red/warm, 15 when walls were blue-green/cool, and 15 when walls were white/neutral. Analysis of covariance of posttest measurements with the pretest as a covariate showed no significant differences among the three groups on performance or scores on anxiety, depression, and arousal. If color of the environment has an effect on work performance or mood, either the effect was too small to be detected with samples of 15 subjects or longer participation than one hour was required. PMID- 8451131 TI - Sidedness in Shotokan karate kata. AB - The 1183 techniques forming the 27 kata (forms) of Shotokan karate, were analysed for left/right bias. Punches/spear-hands, strikes and kicks showed a significant right-sided bias, but not for blocks and the major stances. PMID- 8451132 TI - Posttraumatic stress disorder and mild head trauma: follow-up of a case study. AB - A current conceptual conundrum is the question of whether it is possible to have a co-occurrence of both Posttraumatic Stress Disorder and head trauma. The current report describes the results of behavior therapy and a series of neuropsychological tests for a man who suffered Posttraumatic Stress Disorder and neuropsychological deficits after an automobile accident. A series of neuropsychological test batteries documented considerable improvement. The patient was also treated for Posttraumatic Stress Disorder with behavior therapy so symptoms abated much earlier than the neuropsychological deficits. PMID- 8451133 TI - Paranormal and religious beliefs may be mediated differentially by subcortical and cortical phenomenological processes of the temporal (limbic) lobes. AB - The vectorial hemisphericity concept predicts that endorsements of beliefs in paranormal phenomena are associated with elevated subcortical (complex partial epileptic-like signs) temporal lobe experiences while endorsements of religious beliefs are associated with experiences of the right (cortical) hemispheric equivalent (the sensed presence) of the linguistic sense of self. Partial correlation analyses, which removed the expected shared variance, supported this hypothesis for 400 men and 400 women; religious affiliation did not contribute any statistically significant influence. However, agreements with extreme religious beliefs, such as killing others in God's name, were associated with weekly church attendance and were primarily endorsed by men but not by women. PMID- 8451134 TI - Correlations of the Kahn Intelligence Test and the WAIS--R IQs among mentally retarded adults. AB - Correlations of scores on the WAIS--R and Kahn Intelligence Test: Experimental (KIT) were examined. The 21 subjects were moderately and severely adaptively impaired adults. The WAIS--R is frequently included in the evaluation of moderately and severely retarded adults but its use has been questioned given the problem of statistical floor because institutionalized mentally retarded adults were excluded from the standardization sample. Tasks demand verbal communication and timed performance. The KIT is utilized as a test of intelligence that requires limited verbal skills, is less influenced by cultural/educational factors, and has an adequate statistical floor. Results suggested significantly lower mean scores on the KIT than on WAIS--R. If further evidence supports these conclusions, the KIT may be a valuable instrument in the assessment of moderately and severely retarded adults. PMID- 8451135 TI - Contour lightness and separation effects in the Ebbinghaus illusion. AB - For 48 observers, the central circle of Ebbinghaus figures appeared smaller as the separation between it and the contextual circles increased. Lightness of the contours only affected the illusion when the contextual circles were large and located close to the central circle. An explanation incorporating size contrast and attraction between contours was offered. PMID- 8451136 TI - The paternity of the power law of human motor control. AB - It is pointed out that, contrary to a recent paternity claim, the power law of human motor control was first discovered by this author more than ten years ago. The classical Fitts' law is shown to be a special case of the power law. PMID- 8451137 TI - Individual differences in preference for environmental sounds. AB - 25 typical environmental sounds were presented to 936 Japanese high school students in a written questionnaire to measure their preferences for these sounds. Sex-related, personality-related, and regional differences among preferences were observed for kind of sound. On the other hand, self-rated frequency of hearing each sound in daily life was related to the subjects' residential environment and sex. PMID- 8451138 TI - Relationship among socialization, attitude, and placement with participation in physical activity of students with emotional disorders. AB - 206 students, with emotional disorders, ages 14 to 21 years in mainstreamed and adapted physical education classes, were surveyed concerning their participation in physical activity, attitude toward physical activity, and the influence of significant others in their participation. Significant relations were found between participation in and attitude toward physical activity, influence of social systems, and physical education placement. Subjects showed activity preferences and rates of participation in physical activity similar to those of nondisabled peers. Subjects expressed positive attitudes toward physical activity and indicated that encouragement from parents, siblings, peers, teachers, and coaches was important in their participation. PMID- 8451139 TI - Assessing stressors experienced through news media. AB - The Persian Gulf war of 1991 and the Los Angeles riots of 1992 highlight the importance of better understanding the effects of specific stressors that come to be known to the population solely through the news media. A standard scale to measure or categorize such stressors is suggested as a means of promoting further research. PMID- 8451140 TI - The fallacy of the argument for reduced longevity in left-handers. AB - The fallacy of the argument for reduced longevity in left-handers depends on the use of the writing hand in the assessment of the present generation of elderly people, when writing was not used as a criterion in the early years of the century. A 'thought' experiment demonstrates that a sample of left-handers is likely to be younger than a sample of right-handers alive in the population and this would be true also of the recently deceased. PMID- 8451141 TI - Differential rate of neuropsychological dysfunction in psychiatric disorders: comparison between the Halstead-Reitan and Luria-Nebraska batteries. AB - This report examined the rate of agreement between scores of the Halstead-Reitan and Luria-Nebraska Neuropsychological Batteries in the classification of impaired and nonimpaired performance of 55 schizophrenic and 64 affective disorder patients: 65.2% for schizophrenics and 67.5% for those with affective disorder, with greater impairment on the Halstead-Reitan battery. PMID- 8451142 TI - Processing typical objects in scenes: effects of photographs versus line drawings. AB - The main purpose of this paper is the description of our research into the influence of stimuli (photographs or line-drawing pictures) in perception of scenes. Many researchers have been using the concept of "typically" in an attempt to explain the influence of knowledge structures on processing visual stimuli. We have also tried to examine the influence of typicality on processing objects in environmental scenes. An experiment was carried out using photographs and their equivalent line-drawings. Subjects had to identify objects and associate them with environmental scenes. Our results show that the typicality factor was significant but not the kind of stimuli used (photographs versus line-drawings). We also discussed the use of photographs and line-drawing pictures as stimuli in the identifying process of visual perception. PMID- 8451143 TI - Passive viewing of the Necker cube during massed and distributed practice. AB - Of 24 students from a psychology class in high school 12 were randomly assigned to a Massed Practice group (4 boys, 8 girls each) and 12 to a Distributed Practice group. They viewed a Necker cube for a 3-min. trial on three occasions separated by a week. The Massed Practice group had no rests while the Distributed Practice group rested 1 min. after each 1 min. of viewing. There were no significant differences for total reversals between Massed and Distributed groups on any trial. There were no significant differences between boys and girls on Trials 1 and 2, but on Trial 3 boys reported significantly more reversals than girls. Within each group there was a significant increase in the number of reversals from Trial 1 to Trial 3, indicating learning effects. Rigidity scores did not correlate significantly with the total Necker cube reversals for Trials 1, 2, or 3. The massed and distributed practice effects were not present although learning was noted. Longer rests may be needed for practice effects within trials; long rests of 7 days between trials may account for lack of differences. PMID- 8451144 TI - Influence of young children's learning modalities on their pitch matching. AB - To assess whether the ability to match pitch vocally could be improved through use of learning modalities 1201 children, ages 6 to 9, sang a song while responding visually (seeing high and low visual aids), auditorily (hearing high and low pitches), or kinesthetically (showing high and low with their hands). Analysis indicated the first-grade children using the visual model sang significantly more accurately than the first-graders using either auditory or kinesthetic models. Vocal accuracy with the visual model did not improve after first grade. PMID- 8451145 TI - Predictive validity of a Spanish-language adapted version of the Anton Brenner Developmental Gestalt Test of School Readiness. AB - For an adapted version of the Anton Brenner Developmental Gestalt Test of School Readiness, developed for experimental use in Costa Rica, the present objective was to ascertain its predictive validity. With 312 preschool children during the first semester and at the end of kindergarten, the relationship between test scores and failing or passing first grade was examined and found similar. The average hit rate (percentage of children with and without school problems who were classified correctly) was 84%, the test's sensitivity (percentage of children with difficulties identified correctly) was 23%, and its specificity (percentage of children correctly identified who did not have school problems in first grade) was 97%. The test showed almost a 7:1 ratio for misclassifying false positives and false negatives. It seems advantageous to use the test in the first semester to have time to remedy difficulties during kindergarten. PMID- 8451146 TI - The influence of response factors on the magnitude of angular induction. AB - The angular induction which is manifested in geometric illusions such as the Poggendorff can be quantified by having the subject select a point which appears to be collinear to an oblique line segment. There may be some concern, however, that this operant procedure does not control the distance which is selected by the subject and may introduce nonperceptual sources of response bias. Four experiments, involving 14 subjects, provide evidence that the error, expressed as angular departure from true collinearity, is a constant irrespective of the location of the page which is chosen. Further, this operant procedure provides a valid measure of perceptual bias. PMID- 8451147 TI - Response time and aesthetic preference. AB - This study investigated the relationship of response time and aesthetic preference for 30 college students who participated in learning about the life of Vincent Van Gogh presented by interactive videodisk. No mean difference pre- and post-test in preferences but a significant decrease in response times were observed. There was little relation between preference scores and response times. These effects may be related to the use of the electronic medium, to the duration of instruction (1 1/2 hr.), and to the stability of aesthetic preference. Results are discussed with reference to art programs and to the use of electronic media in instructional settings and in research. PMID- 8451148 TI - Curricular integration at the University of Missouri-Kansas City School of Medicine. AB - In its combined Baccalaureate-M.D. degree program, the University of Missouri Kansas City School of Medicine endeavors to foster interdisciplinary integration by intertwining the humanities, clinical medicine, and basic sciences throughout the curriculum. Analysis over 6 years (1986-1991) of 547 students' scores on comprehensive examinations and ratings of 464 to 478 graduates' clinical abilities suggest that the integrative elements of the curriculum have a counterpart in performance. Such experience would recommend possible steps to encourage interdisciplinary integration at other schools: allow students to acquire disciplinary understandings but offer early clinical exposure for context and relevance, arrange productive repetition of material, pair more with less advanced students for integrated learning, and choose faculty who model integration and expect students to do so. PMID- 8451149 TI - Comments on Hudesman, Page, and Rautiainen's (1992) subliminal psychodynamic activation experiment. AB - Hudesman, et al.'s (1992) contention that their finding and those of Ariam (1979), Parker (1982), and Cook (1985) show that subliminal psychodynamic activation (SPA) can improve academic performance is questioned. Results obtained from experiments using methodological innovations (Fudin, 1986) would allow a clearer interpretation of positive SPA outcomes. PMID- 8451150 TI - The method of reproduction and Mueller-Lyer changes. AB - In a three-variable study of Mueller-Lyer decrement, each of eight independent groups of 10 subjects responded 30 times to one of the two Mueller-Lyer components by the Method of Reproduction. The mean of the initial Out response was significantly greater absolutely than that of the In response. All three interactions were significant. The In figure demonstrated illusion decrement across the 30 trials, but the Out figure demonstrated illusion increment. PMID- 8451151 TI - Attributions (beliefs) and job satisfaction associated with back pain in an industrial setting. AB - We investigated possible differences between management and workers in attributions about the cause and prevention of industrial back pain. 145 employees from upper management, lower management, and blue-collar ranks completed several questionnaires. Age, sex, job satisfaction, and history of back pain were also examined for possible confounding effects. There were significant differences in attributions between job levels, with upper management believing more strongly in causal factors related to the individual, while blue-collar workers attributed back pain more frequently to the work environment. This difference was significant even when the effects of age, sex, job satisfaction, and pain were controlled. A history of back pain increased attributions of cause related to the work environment. Job dissatisfaction increased the risk for back pain nearly sevenfold and dissatisfied people tended to attribute the cause of their pain to the work environment. These results highlight the intricate relationship between attributions, job satisfaction, and pain. Compliance and motivation for interventions might be enhanced by taking into account differences in attributions of cause and effective prevention. PMID- 8451152 TI - Control of goal-oriented, rapid arm movements by individuals with diabetes mellitus. AB - Diabetic subjects completed a series of rapid, goal-directed arm movements under two conditions of unexpected external loading. Evaluation of electromyographic (EMG) patterns revealed that cocontraction and triphasic activity were predominantly associated with inertial and spring loading, respectively. During inertial load responses some EMG patterns indicated a modified cocontraction pattern. Response accuracy was unaffected by type of load but movement time was greater for the inertial load condition. PMID- 8451153 TI - Transcendental Meditation and general meditation are associated with enhanced complex partial epileptic-like signs: evidence for "cognitive" kindling? AB - The Personal Philosophy Inventories of 221 university students who had learned to meditate (about 65% to 70% Transcendental Meditation) were compared to 860 nonmeditators. Meditators displayed a significantly wider range of complex partial epileptic-like signs. Experiences of vibrations, hearing one's name called, paranormal phenomena, profound meaning from reading poetry/prose, and religious phenomenology were particularly frequent among mediators. Numbers of years of TM practice were significantly correlated with the incidence of complex partial signs and sensed presence but not with control, olfactory, or perseverative experiences. The results support the hypothesis that procedures which promote cognitive kindling enhance complex partial epileptic-like signs. PMID- 8451154 TI - Voice onset time of velar stop productions in aged speakers. AB - Voice onset time (VOT) was measured for voiced and voiceless velar stop consonants across three vowel contexts (/i, a, u/) in healthy young adult and older subjects. Analysis showed that mean VOT values for both /k/ and /g/ across the three vowel contexts did not differ between the two groups; however, differences in VOT variability (standard deviation) approached significance; the older subjects exhibited increased variability. This apparent increase in variability may be related to the subtle anatomical and physiological changes with age. PMID- 8451155 TI - Children's use of transitional objects during daily separations from significant caregivers. AB - Attachment behaviors of 105 toddlers were observed as the children separated from significant caregiver(s) at child care. Analysis indicated that children attached to a transitional object and using the object when separating engaged in ritualistic touching behaviors directed at a variety of targets. Results lend some support to the notion of transitional objects facilitating separation and reducing anxiety in mildly stressful situations. PMID- 8451156 TI - Stability of optimism and choice of coping strategy. AB - Dispositional optimism and choice of coping strategies were measured twice to test the hypothesis that optimists and pessimists routinely use different methods of coping with stressful events and that these choices are stable over time. 82 participants completed a measure of optimism (LOT) and of coping strategy choice (COPE) at each of two sessions, four weeks apart. Repeated-measures t tests showed that overall the self-reports of dispositional optimism and all 15 coping strategy factors were stable over the four-week period. In addition, all 16 scales were significantly related to the first administration at follow-up. Regarding the relation between the 15 coping factors and optimism, five remained significantly correlated with optimism at both testings, five remained uncorrelated with optimism at both testings, and five showed minor changes in magnitude of their correlation (and statistical significance) at both testings. PMID- 8451157 TI - Venturesomeness, impulsiveness, and risky behavior among older adolescents. PMID- 8451158 TI - WAIS performance during the acute recovery stage following closed-head injury. AB - WAIS profiles of 50 acute closed head-injured patients were examined and compared with those of 40 psychiatric inpatients. Patients with moderate and severe, but not with mild, head injury differed significantly from the control group on level of subtest performance. There was no significant interaction of group by subtest. The groups also differed significantly on a measure of between-subtest scatter. Discriminant function analysis incorporating measures of within-subtest scatter correctly classified 89% of all subjects. Within the head-injured group Similarities and Block Design scores were elevated, and the Digit Symbol score depressed. These results indicate that closed head-injured patients can be discriminated from psychiatric inpatients on the basis of WAIS performance, but that they do not necessarily show a characteristic WAIS profile. Within-subtest scatter may indicate information-processing deficits. PMID- 8451159 TI - Chronic pain: dynamics and treatment strategies. AB - Chronic pain, which affects an estimated 80 million Americans, has untold effects on personal productivity, self-esteem, functioning of the family, and cost to the healthcare delivery system. The author describes how the nursing process offers an effective framework from which nurses can provide psychosocial care to clients with chronic pain. Helping clients to assume responsibility for their own well being, achieve independence in their lives, and practice healthy coping mechanisms are major goals of such psychosocial care. PMID- 8451160 TI - Scurvy and psychiatric symptoms. AB - Scurvy is not just a disease of the past, but of the present as well. Yet, the possibility of scurvy is often overlooked in assessing a client's mental health status. Prompt recognition and treatment of scurvy can prevent unnecessary diagnostic testing, as well as a delay in treatment. The author presents a case history of a 55-year-old man with scurvy, delusions, and depression. The client's history, course of illness, treatment, and plan of care are discussed. PMID- 8451161 TI - A women's issue: HIV/AIDS. AB - Women have recently been designated as the "at risk" group for HIV/AIDS infection. The author describes the advantages of doing health education with codependent women in group therapy to change risk behaviors. The assumption is made that as women take their learning home, share it with family and friends, and integrate safe sex practices into their lifestyles, the epidemic growth of HIV/AIDS can be undermined. PMID- 8451162 TI - Physiological causes of depression in the elderly. AB - Depression represents the most common psychiatric disorder in the elderly. Physiological processes can often cause depressive symptoms. The psychiatric nurse provides an important role in assisting the depressed elderly client through interventions, such as talking, exercise, touch, and relaxation. PMID- 8451164 TI - The psychosomatic perspective on health and illness: where do we stand? PMID- 8451163 TI - Denial and serious chronic illness--a personal perspective. AB - The author first reviews the literature on denial as it pertains to coping with a serious physical illness. She then shares what she learned about denial when confronted with the diagnosis of multiple sclerosis. She highlights the therapeutic value of denial, as well as potential negative manifestations and consequences of its overusage. Dr. Handron then suggests how the nurse psychotherapist can assist clients to come to terms with the ramifications of a chronic physical illness. PMID- 8451165 TI - Pharmacokinetics and psychopharmacology: application to the geropsychiatric patient. AB - Understanding pharmacokinetics is an important step in the confident administration of psychotropic drugs. Changes in pharmacokinetics have particular implications for the geropsychiatric patient who will experience a variety of physiological changes that could potentially affect the intensity and duration of drug effects. PMID- 8451166 TI - Alcoholism and liver transplantation: ethical and nursing implications. AB - Alcoholism is the major cause of end-stage liver disease, yet only a small portion of alcoholics receive liver transplants. The author discusses the ethical and nursing implications of the rigorous criteria for transplantation that alcoholic clients must meet. A case history of a 36-year-old woman with end-stage liver disease is described to support the author's contention that substance abuse treatment can ultimately have a positive impact on liver transplant candidacy. PMID- 8451167 TI - Intermolecular mRNA-rRNA hybridization and the distribution of potential interaction regions in murine 18S rRNA. AB - Intermolecular hybridization experiments show that murine 18S rRNA and 28S rRNA are capable of forming stable hybrid structures with mRNA from genes p53, c-myc and c-mos from the same species. Both 5'-uncoding and coding oncogene p53 mRNA regions contain fragments interacting with rRNA. Computer analysis revealed 18S rRNA fragments complementary to oligonucleotides frequently met in mRNA, which are potential hybridization regions (clinger-fragments). The distribution of clinger-fragments along 18S rRNA sequence is universal at least for one hundred murine mRNA sequences analyzed. Maximal frequencies of oligonucleotides complementary to 18S rRNA clinger-fragments are reliably (2-3 times) higher for mRNA than for intron sequences and randomly generated sequences. The results obtained suggest a possible role of clinger-fragments in translation processes as universal regions of mRNA binding. PMID- 8451168 TI - Transcription factor IIA stimulates the expression of classical polIII-genes. AB - Protein fractions containing TFIIA, a transcription factor known to be involved in transcription initiation by RNA polymerase II and 5'-regulated polymerase III genes (e.g. U6), were tested for their role in in vitro transcription of classical pol III genes. These fractions were shown to stimulate a basal transcription system, reconstituted from highly purified fractions hTFIIIB and hTFIIIC. We demonstrate that this stimulating activity isolated from HeLa cells coelutes over at least six chromatographic steps with hTFIIA. Moreover the native molecular mass and the stability of this activity against heat treatment are comparable to those of hTFIIA. Finally we show that recombinant TFIIA from Saccharomyces cerevisiae can substitute for the human factor in pol III transcription in vitro which proves that TFIIA is also involved in the efficient expression of classical pol III genes. PMID- 8451169 TI - Evidence for opposite groove-directed curvature of GGGCCC and AAAAA sequence elements. AB - The repetitive sequence (AGGGCCCTAGAGGGGCCC-TAG)n was previously shown to be curved by gel mobility assays. Here we show, using hydroxy radical/DNase I digestion and differential helical phasing experiments that the curvature is directed towards the major groove and is located in the GGGCCC, but not the CTAGAG segments. The effect of the GC step in the context of the GGGCCC motif is apparently about as large as that of AA/TT, i.e. enough to cancel the macroscopic curvature of helically phased A-tracts. These data are in agreement with positive roll-like curvature of the GCC/GGC motif, predicted from nucleosome packing data and the 3D structure of the GGGGCCCC octamer, but they are not in agreement with the dinucleotide-based roll angle values predicted for AG/CT, TA, GG/CC and GC steps. Our results thus indicate the importance of interactions beyond the dinucleotide steps in predictive models of DNA curvature. PMID- 8451170 TI - Two non-histone proteins are associated with the promoter region and histone HI with the transcribed region of active hsp-70 genes as revealed by UV-induced DNA protein crosslinking in vivo. AB - We described here an approach for mapping proteins on any sequence of genomic DNA. UV-induced DNA-protein crosslinking within whole cells and the 'protein image' hybridization technique (1) were applied to test the proteins bound to different regions of the D. melanogaster hsp-70 gene. The histone H1-DNA association with the coding region is shown to be maintained, even during very intensive transcription, but is absent in the promoter. Two non-histone proteins with apparent molecular masses of 50 kD (p50) and 100 kD (p100) are crosslinked only to the active hsp-70 gene regulatory region and preferentially bind to its complementary and coding DNA strands, respectively. PMID- 8451171 TI - A genomic gene for MAP, a ribosome-inactivating protein from Mirabilis jalapa, contains an intron. PMID- 8451172 TI - The second largest subunit of RNA polymerase II from Arabidopsis thaliana. PMID- 8451173 TI - Nucleotide sequence analysis of the ribosomal S12 gene of Mycobacterium intracellulare. PMID- 8451174 TI - A Borrelia burgdorferi homolog of the Escherichia coli rho gene. PMID- 8451175 TI - The human Oct-6 POU transcription factor lacks the first 50 amino acids of its murine counterpart. PMID- 8451177 TI - A rapid and versatile method to synthesize internal standards for competitive PCR. PMID- 8451176 TI - Purification of DNA-binding proteins using tandem DNA-affinity column. PMID- 8451178 TI - Simple and efficient method for directly electroporating Agrobacterium plasmid DNA into wheat callus cells. PMID- 8451179 TI - Detection of UV-induced RNA:protein crosslinks in snRNPs by oligonucleotides complementary to the snRNA. PMID- 8451180 TI - Tissue grinding with ball bearings and vortex mixer for DNA extraction. PMID- 8451181 TI - Compilation, alignment, and phylogenetic relationships of DNA polymerases. PMID- 8451182 TI - Rapid sizing of individual fluorescently stained DNA fragments by flow cytometry. AB - Large, fluorescently stained restriction fragments of lambda phage DNA are sized by passing individual fragments through a focused continuous wave laser beam in an ultrasensitive flow cytometer at a rate of 60 fragments per second. The size of the fluorescence burst emitted by each stained DNA fragment, as it passes through the laser beam, is measured in one millisecond. One hundred sixty four seconds of fluorescence burst data allow linear sizing of DNA with an accuracy of better than two percent over a range of 10 to 50 kbp. This corresponds to analyzing less than 1 pg of DNA. Sizing of DNA fragments by this approach is much faster, requires much less DNA, and can potentially analyze large fragments with better resolution and accuracy than with gel-based electrophoresis. PMID- 8451183 TI - The XylS/AraC family of regulators. AB - At least twenty-seven proteins belong to the XylS/AraC family of prokaryote transcriptional regulators. All members of this family except CelD and TetD are positive transcriptional factors. Three subgroups were distinguished within the family in accordance with the Needleman and Wunsch algorithm. Multiple alignment of these proteins revealed that they shared a high degree of sequence homology at their C-terminal end, where a characteristic conserved motif, whose consensus sequence is I-DIA--GF-S--YF--F---G-TPS--R (where - means any aminoacid), was found. Within the homologous C-terminal region, but outside the above consensus motif, a putative DNA-binding domain organized as a helix-turn-helix motif was located in all regulators. For regulators recognizing chemical signals, the non homologous N-terminal region of these regulators is presumed to contain binding sites for activator molecules that confer specificity. PMID- 8451184 TI - Turbo cloning: a fast, efficient method for cloning PCR products and other blunt ended DNA fragments into plasmids. AB - The method uses a novel plasmid vector, p9lox5, containing a site-specific recombination sequence lox from the lox/Cre recombinase system of bacteriophage P1. There are two distinct stages. Firstly, vector and fragment DNAs are ligated intermolecularly under conditions of macromolecular crowding (15% polyethylene glycol 6000) which accelerate blunt-end joining a thousandfold. Secondly, circular recombinant molecules are efficiently excised from the ligation products by Cre recombinase acting on pairs of lox sites within directly repeated vector molecules flanking insert DNA. Recombinants are introduced into cells conventionally by transformation or electroporation. In both a model system and the cloning of PCR products, yields approaching those obtainable in cohesive-end cloning were achieved. Applications of the technique to cDNA library generation and recovery of DNA from archive material are discussed. PMID- 8451185 TI - Two short basic sequences surrounding the zinc finger of nucleocapsid protein NCp10 of Moloney murine leukemia virus are critical for RNA annealing activity. AB - The 56 amino acid nucleocapsid protein (NCp10) of Moloney Murine Leukemia Virus, contains a CysX2CysX4HisX4Cys zinc finger flanked by basic residues. In vitro NCp10 promotes genomic RNA dimerization, a process most probably linked to genomic RNA packaging, and replication primer tRNA(Pro) annealing to the initiation site of reverse transcription. To characterize the amino-acid sequences involved in the various functions of NCp10, we have synthesized by solid phase method the native protein and a series of derived peptides shortened at the N- or C-terminus with or without the zinc finger domain. In the latter case, the two parts of the protein were linked by a Glycine - Glycine spacer. The in vitro studies of these peptides show that nucleic acid annealing activities of NCp10 do not require a zinc finger but are critically dependent on the presence of specific sequences located on each side of the CCHC domain and containing proline and basic residues. Thus, deletion of 11R or 49PRPQT, of the fully active 29 residue peptide 11RQGGERRRSQLDRDGGKKPRGPRGPRPQT53 leads to a complete loss of NCp10 activity. Therefore it is proposed that in NCp10, the zinc finger directs the spatial recognition of the target RNAs by the basic domains surrounding the zinc finger. PMID- 8451186 TI - Lagging strand DNA synthesis by calf thymus DNA polymerases alpha, beta, delta and epsilon in the presence of auxiliary proteins. AB - By using a defined gapped DNA substrate that mimics a lagging strand of 230 nucleotides and that contains a defined pause site, we have analyzed calf thymus DNA polymerases (pol) alpha, beta, delta, and epsilon in the presence of the three auxiliary proteins proliferating cell nuclear antigen (PCNA), replication factor C (RF-C) and replication protein A (RP-A) for their ability to complete an Okazaki fragment. Pol alpha alone could fill the gap to near completion, but was strongly stopped by the pause site. Addition of low amounts of RP-A resulted in an increased synthesis by pol alpha past the pause site. In contrast, high amounts of RP-A strongly inhibited gap filling by pol alpha. Further inhibition was evident when the two other auxiliary proteins, PCNA and RF-C, were added in addition to RP-A. Pol beta could completely fill the gap without specific pausing and also was strongly inhibited by RP-A. PCNA and RF-C had no detectable effect on pol beta. Pol delta, relied as expected, on all three auxiliary proteins for complete gap filling synthesis and could, upon longer incubation, perform a limited amount of strand displacement synthesis. Pol epsilon core enzyme was able to fill the gap completely, but like pol alpha, essentially stopped at the pause site. This pausing could only be overcome upon addition of PCNA, RF-C and E. coli single-stranded DNA binding protein. Thus pol epsilon holoenzyme preferentially synthesized to the end of the gap without pausing. Ligation of the DNA products indicated that pol beta core enzyme, pol delta and pol epsilon holoenzymes (but not pol alpha and pol epsilon core enzyme) synthesized products that were easily ligatable. Our results indicate that pol epsilon holoenzyme fills a defined lagging strand gapped template to exact completion and is able to pass a pause site. The data favour the hypothesis of Burgers (Burgers, P.M.J. (1991) J. Biol. Chem. 266, 22698-22706) that pol epsilon might be a candidate for the second replication enzyme at the lagging strand of the replication fork. PMID- 8451187 TI - The silent P mating type locus in fission yeast contains two autonomously replicating sequences. AB - We show that in fission yeast two DNA fragments at the silent P mating type locus provide plasmids with the capability of autonomous replication. Bacterial vectors containing these sequences replicate in a polymeric form in fission yeast very much like plasmids with the commonly used replication sequence ars1, do. There are, however, several differences between the two new ars sequences. The percentage of cells containing the plasmid during selection, the plasmid copy number and the plasmid segregation during mitosis are all dependent on the choice of the ars sequence. A DNA fragment with ars activity from the left side of the silent P cassette represses the expression of the marker gene, ura4+, at least three hundred fold compared to plasmids containing only the other new ars sequence or only ars1. The importance of replication in this promoter independent transcriptional regulation is further substantiated by the fact that the repression is partially released in the presence of ars1 on the same plasmid. PMID- 8451188 TI - Identification of the nucleotide sequence recognized by the cAMP-CRP dependent CytR repressor protein in the deoP2 promoter in E. coli. AB - In E. coli repression of transcription initiation by the CytR protein relies on CytR-DNA interactions as well as on interactions between CytR and the cAMP-CRP activator complex. To identify the nucleotide sequence recognized by CytR, mutants of the deoP2 promoter with a reduced regulatory response to CytR have been isolated. Five single bp mutation derivatives of deoP2 with a 2-5-fold decrease in CytR regulation have been characterized. In vitro, the only effect of the mutations was a decrease in the binding affinity of CytR, and a clear correlation was observed between the reduction in CytR regulation in vivo and the reduction in CytR binding in vitro. The mutations all reside in a sequence element that contains an imperfect direct as well as an imperfect inverted repeat. As the active form of CytR, most likely, is an oligomer with two-fold rotational symmetry, CytR probably interacts with the inverted repeat. Degenerate versions of the inverted repeat are present in all CytR binding sites characterized so far, however, the distance between the half-sites varies. PMID- 8451189 TI - The M.AluI DNA-(cytosine C5)-methyltransferase has an unusually large, partially dispensable, variable region. AB - The DNA methyltransferase of the AluI restriction-modification system, from Arthrobacter luteus, converts cytosine to 5-methylcytosine in the sequence AGCT. The gene for this methyltransferase, aluIM, was cloned into Escherichia coli and sequenced. A 525-codon open reading frame was found, consistent with deletion evidence, and the deduced amino acid sequence revealed all ten conserved regions common to 5-methylcytosine methyltransferases. The aluIM sequence predicts a protein of M(r) 59.0k, in agreement with the observed M(r), making M.AluI the largest known methyltransferase from a type II restriction-modification system. M.AluI also contains the largest known variable region of any monospecific DNA methyltransferase, larger than that of most multispecific methyltransferases. In other DNA methyltransferases the variable region has been implicated as the sequence-specific target recognition domain. An in-frame deletion that removes a third of this putative target-recognition region leaves the Alu I methyltransferase still fully active. PMID- 8451190 TI - Functional analysis of a C. elegans trans-splice acceptor. AB - The rol-6 gene is trans-spliced to the 22 nt leader, SL1, 173 nt downstream of the transcription start. We have analyzed splicing in transformants carrying extrachromosomal arrays of rol-6 with mutations in the trans-splice acceptor site. This site is a close match to the consensus, UUUCAG, that is highly conserved in both trans-splice and intron acceptor sites in C. elegans. When the trans-splice site was inactivated by mutating the perfectly-conserved AG, trans splicing still occurred, but at a cryptic site 20 nt upstream. We tested the frequency with which splicing switched from the normal site to the cryptic site when the pyrimidines at this site were changed to A's. Since most C. elegans 3' splice sites lack an obvious polypyrimidine tract, we hypothesized that these four pyrimidines might play this role, and indeed mutation of these bases caused splicing to switch to the cryptic site. We also demonstrated that a major reason the downstream site is normally favored is because it occurs at a boundary between A+U rich and non-A+U rich RNA. When the RNA between the two splice sites was made less A+U rich, splicing occurred preferentially at the upstream site. PMID- 8451191 TI - SmtB is a metal-dependent repressor of the cyanobacterial metallothionein gene smtA: identification of a Zn inhibited DNA-protein complex. AB - The smt locus of Synechococcus PCC 7942 contains a metal-regulated gene (smtA), which encodes a class II metallothionein, and a divergently transcribed gene, smtB, which encodes a repressor of smtA transcription. Regions containing cis acting elements required for efficient induction, and required for smtB-dependent repression, of the smtA operator-promoter were identified. Specific interactions between proteins extracted from Synechococcus PCC 7942 and defined regions surrounding the smtA operator-promoter were detected by electrophoretic mobility shift assays. Three metallothionein operator-promoter associated complexes were identified, one of which (MAC1) showed Zn-dependent dissociation and involved a region of DNA immediately upstream of smtA. Treatment with Zn-chelators facilitated re-association of MAC1 in vitro. MAC1 was not observed in extracts from smt deficient mutants but was restored in extracts from mutants complemented with a plasmid borne smtB. SmtB is thus required for the formation of a Zn responsive complex with the smt operator-promoter and based upon the predicted structure of SmtB we propose direct SmtB-DNA interaction exerting metal-ion inducible negative control. PMID- 8451192 TI - Basal level transcription of the histone H1(0) gene is mediated by a 80 bp promoter fragment. AB - The replacement histone H1(0) of the H1 group, known to interact with general transcription factors, has been found associated with transcriptionally repressed chromatin. Transcription of the gene in F9 stem cells is low but can be stimulated by treating the cells with retinoic acid. Using mutant deletions, we now demonstrate that basal level transcription in F9 cells is mediated by an 80 bp DNA fragment, located 430 bp upstream of the TATA box, which does not include the retinoic acid responsive element (RARE) known to bind retinoic acid receptors and stimulate transcription from an heterologous promoter after retinoic acid treatment. By footprinting, DMS interference, site-directed mutagenesis and UV cross linking techniques we demonstrate that at least two nuclear factors, with MW of 90,000 and 30,000, bind to the 80 bp fragment and that this binding is necessary for transcription. Furthermore, positioning of this fragment upstream of the HSV-tk gene promoter stimulates transcription 2-3 times over control values, far less than the activity observed for this fragment in the homologous promoter, indicating that full activity of this fragment requires sequences located in the proximal part of the promoter. PMID- 8451193 TI - The main early and late promoters of Bacillus subtilis phage phi 29 form unstable open complexes with sigma A-RNA polymerase that are stabilized by DNA supercoiling. AB - Most Escherichia coli promoters studied so far form stable open complexes with sigma 70-RNA polymerase which have relatively long half-lives and, therefore, are resistant to a competitor challenge. A few exceptions are nevertheless known. The analysis of a number of promoters in Bacillus subtilis has suggested that the instability of open complexes formed by the vegetative sigma A-RNA polymerase may be a more general phenomenon than in Escherichia coli. We show that the main early and late promoters from the Bacillus subtilis phage phi 29 form unstable open complexes that are stabilized either by the formation of the first phosphodiester bond between the initiating nucleoside triphosphates or by DNA supercoiling. The functional characteristics of these two strong promoters suggest that they are not optimized for a tight and stable RNA polymerase binding. Their high activity is probably the consequence of the efficiency of further steps leading to the formation of an elongation complex. PMID- 8451194 TI - Phosphorylation of human hnRNP protein A1 abrogates in vitro strand annealing activity. AB - In HeLa cells metabolically labeled in vivo with [32P] orthophosphate in the presence of okadaic acid the concentration of phosphorylated A1 protein was increased significantly as compared to controls. Purified recombinant hnRNP protein A1 served as an excellent substrate in vitro for the catalytic subunit of cAMP-dependent protein kinase (PKA) and for casein kinase II (CKII). Thin layer electrophoresis of A1 acid hydrolysates showed the protein to be phosphorylated exclusively on serine residue by both kinases. V8 phosphopeptide maps revealed that the target site(s) of in vitro phosphorylation are located in the C-terminal region of A1. Phosphoamino acid sequence analysis and site directed mutagenesis identified Ser 199 as the sole phosphoamino acid in the protein phosphorylated by PKA. Phosphorylation introduced by PKA resulted in the suppression of the ability of protein A1 to promote strand annealing in vitro, without any detectable effect on its nucleic acid binding capacity. This finding indicates that phosphorylation of a single serine residue in the C-terminal domain may significantly alter the properties of protein A1. PMID- 8451195 TI - DNA-histone interactions are sufficient to position a single nucleosome juxtaposing Drosophila Adh adult enhancer and distal promoter. AB - The alcohol dehydrogenase gene (Adh) of Drosophila melanogaster is transcribed from two tandem promoters in distinct developmental and tissue-specific patterns. Both promoters are regulated by separate upstream enhancer regions. In its wild type context the adult enhancer specifically stimulates only the distal promoter, approximately 400 bp downstream, and not the proximal promoter, which is approximately 700 bp further downstream. Genomic footprinting and micrococcal nuclease analyses have revealed a specifically positioned nucleosome between the distal promoter and adult enhancer. In vitro reconstitution of this nucleosome demonstrated that DNA-core histone interactions alone are sufficient to position the nucleosome. Based on this observation and sequence periodicities in the underlying DNA, the mechanism of positioning appears to involve specific DNA structural features (ie flexibility or curvature). We have observed this nucleosome positioned early during development, before tissue differentiation, and before non-histone protein-DNA interactions are established at the distal promoter or adult enhancer. This nucleosome positioning element in the Adh regulatory region could be involved in establishing a specific tertiary nucleoprotein structure that facilitates specific cis-element accessibility and/or distal promoter-adult enhancer interactions. PMID- 8451196 TI - Activity of yeast FLP recombinase in maize and rice protoplasts. AB - We have demonstrated that a yeast FLP/FRT site-specific recombination system functions in maize and rice protoplasts. FLP recombinase activity was monitored by reactivation of beta-glucuronidase (GUS) expression from vectors containing the gusA gene inactivated by insertion of two FRTs (FLP recombination targets) and a 1.31 kb DNA fragment. The stimulation of GUS activity in protoplasts cotransformed with vectors containing FRT inactivated gusA gene and a chimeric FLP gene depended on both the expression of the FLP recombinase and the presence and structure of the FRT sites. The FLP enzyme could mediate inter- and intramolecular recombination in plant protoplasts. These results provide evidence that a yeast recombination system can function efficiently in plant cells, and that its performance can be manipulated by structural modification of the FRT sites. PMID- 8451197 TI - IGH minisatellite suppression of USF-binding-site- and E mu-mediated transcriptional activation of the adenovirus major late promoter. AB - The 50bp repeat unit of the minisatellite within the DH-JH interval of the human immunoglobulin heavy chain locus binds a nuclear factor present in a wide variety of cell types. The binding site contains the myc/HLH motif, CACGTG, and represents a 15 of 17 base match for the USF/MLTF binding site adjacent to the adenovirus major late promoter (MLP). Unlike the USF/MLTF site, the IGH minisatellite possesses no enhancer activity. However, it can significantly suppress, in cis and in trans, USF-site-mediated transcriptional activation of the MLP. In murine myeloma cells, the IGH minisatellite can suppress, in trans, MLP activation by the murine heavy chain gene enhancer, E mu. These activities potentially represent a DNA-based form of squelching. PMID- 8451198 TI - A unique restriction endonuclease, BcgI, from Bacillus coagulans. AB - We have purified and characterized a new restriction endonuclease, BcgI, which has properties unlike those of the three recognized classes of restriction enzymes. BcgI was isolated from Bacillus coagulans, and it recognizes the sequence CGAN6TGC. BcgI cleaves double stranded DNA on both strands upstream and downstream of the recognition sequence, so that the recognition sequence is released as a 34-base pair fragment with 2-base 3'-extensions. Mg++ and S adenosylmethionine are required for cleavage. Sinefungin, a structural analogue of AdoMet which generally inhibits methylase activity, can replace AdoMet in the cleavage reaction. The apparent binding constant (Kappd) for AdoMet is about 100 nM, while the KappD for sinefungin is about 500 nM. PMID- 8451199 TI - Cell cycle regulation of the glyceraldehyde-3-phosphate dehydrogenase/uracil DNA glycosylase gene in normal human cells. AB - The cell cycle regulation of the glyceraldehyde-3-phosphate dehydrogenase (GAPDH)/uracil DNA glycosylase (UDG) gene was examined in normal human cells. Steady state RNA levels were monitored by Northern blot analysis using a plasmid (pChug 20.1) which contained the 1.3 kb GAPDH/UDG cDNA. The biosynthesis of the 37 kDa GAPDH/UDG protein was determined using an anti-human placental GAPDH/UDG monoclonal antibody to immunoprecipitate the radiolabeled protein. Increases in steady state GAPDH/UDG mRNA levels were cell cycle specific. A biphasic pattern was observed resulting in a 19-fold increase in the amount of GAPDH/UDG mRNA. The biosynthesis of the 37 kDa GAPDH/UDG protein displayed a similar biphasic regulation with a 7-fold increase. Pulse-chase experiments revealed a remarkably short half life of less than 1 hr. for the newly synthesized 37 kDa protein, comparable to that previously documented for a number of oncogenes. GAPDH/UDG mRNA levels were markedly reduced at 24 hr. when DNA synthesis was maximal. These results define the GAPDH/UDG gene as cell cycle regulated with a characteristic temporal sequence of expression in relation to DNA synthesis. The cell cycle synthesis of a labile 37 kDa monomer suggests a possible regulatory function for this multidimensional protein. Further, modulation of the GAPDH/UDG gene in the cell cycle may preclude its use as a reporter gene when the proliferative state of the cell is not kept constant. PMID- 8451201 TI - National trends in diabetes. An epidemiologic perspective. AB - Diabetes mellitus is a major public health problem that affects all of society regardless of age, sex, ethnicity, or race. Moreover, diabetes and its related complications inflict destruction at all stages of the life cycle: newborn and infant, childhood, during adolescent growth and development, during pregnancy, in the maturing adult, and during later adult life. As health care professionals, we need to recognize the magnitude and seriousness of this disease and act as catalyst in providing care to those individuals with diabetes. PMID- 8451202 TI - Issues in diabetes education. AB - Issues in diabetes education are far-reaching. Professional preparation along with management issues and dilemmas are discussed in this article; they often precede the teaching/learning experience. In all instances, the diabetes educator must be a catalyst who continuously replenishes knowledge to those with diabetes. The gratification of facilitating independent living is a powerful motivation for those in this profession. PMID- 8451200 TI - Three new members of the RNP protein family in Xenopus. AB - Many RNP proteins contain one or more copies of the RNA recognition motif (RRM) and are thought to be involved in cellular RNA metabolism. We have previously characterized in Xenopus a nervous system specific gene, nrp1, that is more similar to the hnRNP A/B proteins than to other known proteins (K. Richter, P. J. Good, and I. B. Dawid (1990), New Biol. 2, 556-565). PCR amplification with degenerate primers was used to identify additional cDNAs encoding two RRMs in Xenopus. Three previously uncharacterized genes were identified. Two genes encode hnRNP A/B proteins with two RRMs and a glycine-rich domain. One of these is the Xenopus homolog of the human A2/B1 gene; the other, named hnRNP A3, is similar to both the A1 and A2 hnRNP genes. The Xenopus hnRNP A1, A2 and A3 genes are expressed throughout development and in all adult tissues. Multiple protein isoforms for the hnRNP A2 gene are predicted that differ by the insertion of short peptide sequences in the glycine-rich domain. The third newly isolated gene, named xrp1, encodes a protein that is related by sequence to the nrp1 protein but is expressed ubiquitously. Despite the similarity to nuclear RNP proteins, both the nrp1 and xrp1 proteins are localized to the cytoplasm in the Xenopus oocyte. The xrp1 gene may have a function in all cells that is similar to that executed by nrp1 specifically within the nervous system. PMID- 8451203 TI - The concept of health. Rural perspectives. AB - An understanding of the client's concept of health is necessary to conduct relevant and effective health assessment, planning, intervention, and evaluation. Client health concepts are affected by place of residence and further colored by specific community and individual level variations including occupation, education, subculture, age, gender, and health status. Rural nursing practice can be improved through knowledge of the health perceptions and definitions held by the rural clients to be served. Nursing, as a discipline, has traditionally emphasized the need to understand the client's perspective and to develop mutually agreed on health goals in collaboration with the client. Rural nursing practice offers unique opportunities to consider meanings of health within the environmental context. Further, it challenges nurses to work hand-in-hand with clients to develop strategies that fit the context, and thus effectively address rural health care needs. PMID- 8451204 TI - The uniqueness of rural nursing. AB - Rural nursing is a unique and challenging field of nursing that requires a "special breed" of nurse that is committed to high quality, comprehensive care at the individual, family, and community levels. The unique characteristics of rural nursing include close interaction with the community, a truly generalist approach, and increased autonomy, cohesiveness, and community visibility. This area of specialty practice requires nurses to be highly competent and well prepared in all aspects of professional practice. Certainly, the demands of rural nursing are great, as are the benefits. Rural nursing can indeed be the essence of what nursing should be. PMID- 8451205 TI - Community health nursing in rural and frontier counties. AB - This article discusses the nature and problems of community health nursing practice in large, sparsely populated rural areas. Data were obtained from more than 30 rural community health nurses practicing in a variety of settings. Salient characteristics and a beginning descriptive theory of rural community health nursing practice are presented. PMID- 8451206 TI - Rural-based critical care nursing. AB - A review of rural-based critical care nursing has demonstrated that quality critical care can be delivered within the constraints of rural practice. The barriers most often found affecting rural care have been described. Proven realistic strategies to these barriers have been delineated. A distinct advantage of rural nursing is the increased amount of change and influence a single nurse can have on the community health care system. The rural nurse manager has the opportunity to create a critical care nursing service with high levels of accountability, that can quickly respond to change, and that produces quality patient care. By accomplishing these goals, rural critical care nurses will leave a meaningful legacy of enhanced lives and improved health for their rural communities. PMID- 8451207 TI - Rural women. Lifestyle and health status. AB - This article presented a "snapshot" of the concerns and issues confronting America's rural women. The discussion highlighted demographic, economic, and sociocultural factors that impact the health status of women living in diverse rural environments. Recommendations were proposed to assist nurses to better address the health concerns of these women. PMID- 8451208 TI - Promoting maternal infant health in rural communities. The Rural Health Outreach Program. AB - RHOP is a nurse-managed community-based program that uses a variety of approaches to reduce infant mortality and improve maternal child health. In a rural area, representative of much of the rural South, which has a persistent record of poor maternal-child outcomes, the program is using university and community resources to make a difference. The goal is to empower the community to help it help itself using all the available resources. The initial outcome data indicate that these positive changes are happening and can be the site for future activities by those in the community as well as the university. Future plans include involving more departments at the university in the program and expanding services to three additional counties. Graduate students and faculty are becoming interested in conducting research using RHOP activities as a base, and future grants are being considered to expand into new areas such as substance abuse and cancer prevention. PMID- 8451209 TI - Nursing in rural Native American communities. AB - This article discusses the importance of cultural sensitivity in providing nursing services to Native Americans. This necessitates general information about cultural universals that transcend specific tribes as well as cultural-specific knowledge. Cultural sensitivity also requires an understanding of the centuries long oppression of Native Americans and their cultures by the dominant society. PMID- 8451210 TI - Rural elderly individuals. Strategies for delivery of nursing care. AB - This article has presented nursing care strategies for rural elderly persons at the individual and community level. The approach for the strategies was accomplished through presentation of Lawton and Nahemow's Ecological Model of Adaptation and Aging. Competencies of older rural adults and their physical, personal, and social environment were explored using current available literature. Nurses are and can play a key role in maintaining and promoting the health of rural elderly persons. PMID- 8451211 TI - HIV infection in traditional rural communities. AB - The challenge to rural nurses to deliver knowledgeable and skilled nursing and health care to individuals with HIV infection and AIDS is indeed tremendous. Isolation of rural communities and health care facilities coupled with limited resources, financial concerns, conservative values of many traditional rural communities, and the tendency to exclude those who do not conform to community norms make it difficult to integrate the individual with HIV disease into the rural health care delivery system fully. Issues of particular concern to the rural nurse include maintenance of client confidentiality, obtaining and maintaining current knowledge and skills necessary to the provision of quality HIV nursing care, management of complex client health care problems, and provision of appropriate support services. Rural nurses must be innovative and creative in developing mechanisms to deal with these concerns. In addition, because rural nurses are well respected by the community and viewed as possessing a great deal of expertise in the delivery of health care, they are well positioned to provide leadership to the community in developing educational and care strategies to more effectively provide HIV care. Indeed, the delivery of high-quality HIV care in rural areas across the United States will likely depend on the expertise and leadership provided by rural nurses. PMID- 8451212 TI - Trends and issues for cancer care in rural communities. AB - Rural oncology nursing practice combines state-of-the-art oncology skills and knowledge with the opportunity to care for neighbors and friends. Challenges include limited access to specialized health care, coordination of services, and maintenance of continuity of care for patients. Rural oncology nurses are faced with limited opportunities for specialty education, limited resources, few local colleagues, and unique care issues. Rural cancer nursing, however, can be creative and exciting. This article provides an overview of relevant rural health issues, challenges in providing oncology care in rural locations, and strategies for promoting oncology nursing practice in rural settings. PMID- 8451213 TI - Type II non-insulin-dependent diabetes mellitus. AB - Type II non-insulin-dependent diabetes mellitus (NIDDM) occurs predominantly in adults, especially in those individuals over age 30. This disease was formerly called maturity-onset or adult-onset diabetes. A subclass of NIDDM was devised, however, for those families in which children, adolescents, or young adults develop what is referred to as maturity-onset diabetes of the young. This article reviews issues related to treatment modalities for those with type II NIDDM, including dietary management, physical activity, and pharmacologic therapy. PMID- 8451214 TI - Management of agricultural injuries and illness. AB - Until recently, rural health care nursing issues had not been widely addressed. Appropriate concerns for an ill or injured worker in an urban setting are compounded in the rural setting with its isolation and lack of resources. Farming is very diversified, and different parts of the country face different types of problems. Nurses in the rural community have a responsibility to learn as much as possible about the agricultural hazards common to their area. Health care professionals must be able to make rapid, accurate assessments of the injured or ill farmer, taking into account the nature of the machine and environmental factors that may cause additional problems. Proper care of the injured or ill farmer must be initiated at the rural hospital for optimal recovery to take place. PMID- 8451215 TI - Children and adolescents with diabetes. AB - IDDM in children and adolescents requires that complex daily management skills be learned by children and their families. Insulin administration, nutrition therapy, and daily monitoring place the burden of self-management on parents and children, who already may be stressed. The unrelenting care required to observe and treat young children produces anxiety in parents whose children are potentially poised between hypoglycemia and DKA. Health care professionals must understand the dynamic nature of childhood diabetes and not underestimate the impact on specific developmental levels or the amount of support and education required. PMID- 8451216 TI - The challenges of diabetes and older adults. AB - Diabetes is a chronic illness that affects a disproportionate number of older adults and members of ethnic minorities. It is an illness that requires long-term active patient participation to maintain metabolic control and challenges both the patient and health care provider. The need for the patient to carry out daily self-care behaviors is no less important simply because the person is older. Older adults, however, experience unique challenges because of the physical and functional changes that may be imposed by the aging process and the prevalence of multiple chronic illnesses and complications. Because diabetes self-care is carried out within the context of all aspects of a person's life, it is important, then, for the health professional to recognize these social, functional, and psychological challenges. All aspects of physical, functional, and psychosocial status need to be taken into account, and diabetes education needs to be provided based on jointly identified goals, interests, abilities, and needs. PMID- 8451217 TI - Quality assurance for blood glucose monitoring. The balance of feasibility and standards. AB - Capillary BGM is a test performed by persons with diabetes as well as health care professionals, i.e., nonlaboratory personnel. Although there are specific actions to be taken to enhance the quality of the test results, these recommendations are frequently not followed. Because therapeutic regimens for medication, diet, and exercise may be changed based on the BGM data and because there is a possibility of adverse outcome to a patient with erroneous results, assuring the quality of the data is reasonable. The challenge to nurses is to make what is reasonable also feasible and practical. PMID- 8451218 TI - Chronic complications of diabetes mellitus. AB - This article addresses the long-term or chronic complications of diabetes mellitus, including macroangiopathy, microangiopathy, and neuropathy, with a special emphasis on the insensate foot frequently seen in patients with diabetes. This article presents nursing strategies for assessment and suggestions for effective nursing interventions related to these complications. It also identifies some strategies for preventing further complications. PMID- 8451219 TI - Diabetes and minority populations. Focus on Mexican Americans. AB - Hispanic American people in the United States represent a diverse group by origin, with Mexican Americans comprising the largest and fastest growing segment of this minority population. Whereas few studies have been undertaken to explore diabetes in other Hispanic American groups, several population-based studies have yielded outcomes reflecting significant prevalence and incidence of type II NIDDM among Mexican American people. These rates underscore the need for increasing attention toward understanding dimensions of the population that may effect positive health outcomes. Such is the role of cultural nursing as it relates to diabetes care and education of this population. Cultural nursing embodies a holistic approach to care with focus on assessment of cultural dimensions and attributes as they pertain to the individual with diabetes. Although cultural attributes may vary by ethnic origin, person, and region of the country, the diabetes nurse educators' appreciation of the cultural domain of Hispanicism best provides the patient with the opportunity to effect enactment of necessary diabetes self-care behaviors. PMID- 8451220 TI - Type I diabetes and insulin therapy. AB - Intensive insulin therapy is composed of an entire therapeutic program of diabetes management. One component of that program is a multiple-component insulin regimen. There are several important pharmacokinetic issues that must be appreciated when prescribing insulin. These include differences in absorption characteristics between animal and human insulin, variations in intraindividual insulin absorption, the influence of injection sites on insulin absorption, and lag time. Only physiologic insulin regimens should be used in patients with type I diabetes, and there are advantages and disadvantages to the various available options. There are theoretic reasons why CSII may be better for many patients. Finally, the nurse specialist/educator who is initiating the insulin therapy should be familiar with the general guidelines for the various insulin regimens in addition to implementing appropriate diabetes algorithms. PMID- 8451221 TI - Nutritional management of diabetes. AB - The ideal therapeutic diet for diabetes mellitus is currently unknown; however, it continues as a cornerstone of treatment for this complex disease. Dietary guidelines dictate a prudent, healthy diet that is recommended for all healthy people, with or without diabetes. Individuals with diabetes are counseled according to their life-style demands and presence of complications. In fact, there may be as many diets for diabetes as people with diabetes, based on the many manifestations, presentations, and complications of diabetes mellitus. Nutrition research in diabetes is a viable pursuit and will continue to generate interest and further modifications until the cure for diabetes is found. PMID- 8451222 TI - [Quantitative determination of steroid hormone receptors in breast cancer tissue outside tumor centers]. PMID- 8451223 TI - [Carcinoma with carcinoid differentiation. Differential diagnostic interpretation of an unusual malignant breast tumor]. PMID- 8451224 TI - [Genetic morphologic lethal syndrome. Nosologic classification]. PMID- 8451225 TI - [Meckel-Gruber syndrome]. PMID- 8451226 TI - [Hydrolethalus syndrome]. PMID- 8451227 TI - [Myiasis in female travelers to the tropics]. AB - Myiasis is a rare disease in Europe and the USA; it is defined by the development of parasitic, mostly tropical maggots in the human body. They are best identified by the pattern of their terminal spiracles and the shape of their stigmal plates. In spite of the size of the larvae of Cordylobia anthropophaga, there is only low grade inflammation; the clinical course is benign. PMID- 8451228 TI - [Several different types of amyloid in a 93-year-old female patient: case report of an autopsy case]. PMID- 8451229 TI - [Keratoacanthoma with infiltration of nerve sheaths]. PMID- 8451230 TI - [Isolated mesenterial fibromatosis without Gardner syndrome--a postoperative complication?]. PMID- 8451231 TI - [Endometrial curettage with metastasis of a clinically inapparent stomach cancer- a case report]. PMID- 8451232 TI - ["The current status of grading in breast cancer." Comments on the article by R. Bassler, W. Bocker, P. Hermanek, H. Pickartz, K. Prechtel, A. Schauer, H.-G. Schnurch, H. E. Stegner]. PMID- 8451233 TI - [Accessory conduction system pathways of the heart as a cause of arrhythmia induced cardiac death]. PMID- 8451234 TI - The quaternary structure of carbonmonoxy hemoglobin ypsilanti. AB - We present a geometric analysis of the allosteric interface in the new Y state quaternary structure observed in liganded mutant hemoglobin Ypsilanti (beta 99 Asp-->Tyr) by Smith, F.R., Lattman, E.E., Carter, C.W., Jr. (Proteins 10:81-91, 1991). The classical T to R quaternary structure change being a rotation of alpha beta dimers about an axis which is approximately parallel to the dimer axis of pseudosymmetry, the new quaternary structure is obtained by applying to R an additional rotation about an axis orthogonal to the first. This suggests that Y is a modified R state rather than an intermediate on the T to R pathway. Computer docking experiments designed to simulate the quaternary structure change support this suggestion. PMID- 8451235 TI - Insertion of peptide chains into lipid membranes: an off-lattice Monte Carlo dynamics model. AB - A combination of dynamic Monte Carlo simulation techniques with a hydropathy scale method for the prediction of the location of transmembrane fragments in membrane proteins is described. The new hydropathy scale proposed here is based on experimental data for the interactions of tripeptides with phospholipid membranes (Jacobs, R.E., White, S.H. Biochemistry 26:6127-6134, 1987) and the self-solvation effect in protein systems (Roseman, M.A. J. Mol. Biol. 200:513 522, 1988). The simulations give good predictions both for the state of association and the orientation of the peptide relative to the membrane surface of a number of peptides including Magain2, M2 delta, and melittin. Furthermore, for Pf1 bacteriophage coat protein, in accord with experiment, the simulations predict that the C-terminus forms a transmembrane helix and the N-terminus forms a helix which is adsorbed on the surface of the bilayer. Finally, the present series of simulations provide a number of insights into the mechanism of insertion of peptides into cell membranes. PMID- 8451236 TI - Crystallization and preliminary X-ray diffraction studies of dogfish C-reactive protein. AB - Crystals of dogfish (Mustelus canis) C-reactive protein were obtained through vapor phase equilibration using the sitting drop rod technique with ammonium sulfate as the precipitating agent. The space group was determined to be P1 (triclinic lattice) with unit cell dimensions of a = 82.91, b = 92.25 and c = 103.40 A; alpha = 83.36 degrees, beta = 89.76 degrees, and gamma = 81.30 degrees. These crystals diffract to about 2.6 A resolution and contain two hexamers in the asymmetric unit. PMID- 8451237 TI - Preparation and initial characterization of crystals of the photoprotein aequorin from Aequorea victoria. AB - Crystals of recombinant aequorin, the photoprotein from the jellyfish Aequorea victoria, have been grown from solutions containing sodium phosphate. The crystals grow as thin plates which diffract to beyond 2.2 A resolution. The crystals are orthorhombic, space group P2(1)2(1)2(1); the axes are a = 89.1(1), b = 88.4(1), and c = 52.7(1) A. The asymmetric unit contains two molecules. Crystals exposed to calcium ion solutions emit a steady glow and slowly deteriorate, confirming that the crystals consist of a charged, competent photoprotein. This represents the first successful preparation of single crystals of a photoprotein suitable for diffraction analysis. PMID- 8451238 TI - Characterization of proline-containing alpha-helix (helix F model of bacteriorhodopsin) by molecular dynamics studies. AB - Many of the bilayer spanning segments of membrane transport proteins contain proline residues, and most of them are believed to occur in alpha-helical form. A proline residue in the middle of an alpha-helix is known to produce a bend in the helix, and recent studies have focused on characterizing such a bend at atomic level. In the present case, molecular dynamics (MD) studies are carried out on helix F model of bacteriorhodopsin (BR) Ace-(Ala)7-Trp-(Ala)2-Tyr-Pro-(Ala)2-Trp- (Ala)8-NHMe and compared with Ace-(Ala)7-Trp-(Ala)2-Tyr-(Ala)3-Trp-(Ala)8-NHMe in which the proline is replaced by alanine. The bend in the helix is characterized by structural parameters such as kink angle (alpha), wobble angle (theta), virtual torsion angle (rho), and the hydrogen bond distance d (Op-3 ... Np+1). The average values and the flexibility involved in these parameters are evaluated. The correlation among the bend related parameters are estimated. The equilibrium side chain orientations of tryptophan and tyrosine residues are discussed and compared with those found in the recently proposed model of bacteriorhodopsin. Finally, a detailed characterization of the bend in terms of secondary structures such as alpha I, alpha II and goniometric helices are discussed, which can be useful in the interpretation of the experimental results on the secondary structures of membrane proteins involving the proline residue. PMID- 8451239 TI - Crystal structures of two mutants of adenylate kinase from Escherichia coli that modify the Gly-loop. AB - Two mutants of adenylate kinase from Escherichia coli have been crystallized and analyzed by X-ray diffraction at resolutions of 3.4 and 2.4 A, respectively. These mutants are Pro-9-->Leu and Gly-10-->Val. They were selected for their positions in the highly conserved Gly-loop forming a giant anion hole for the beta-phosphate of ATP (GTP) in adenylate kinases, H-ras-p21, and other nucleotide binding proteins. Mutants at these positions of H-ras-p21 cause cancer. In adenylate kinase these mutations cause smallish changes at the active site. Relating the structural changes to the known changes in catalysis indicates that these mutants hinder the induced-fit movements. As a side result we find that mutant Pro-9-->Leu and wild-type form one very similar crystal packing contact that is crystallographic in one case and noncrystallographic in the other, while all other packing contacts and the space groups are quite at variance. PMID- 8451240 TI - Thermodynamic integration calculations of binding free energy difference for Gly 169 mutation in subtilisin BPN'. AB - The binding free energy difference for the Gly-169-->Ala-169 (G169A) mutation in subtilism BPN' complexed with a tripeptide substrate analogue is explored using the thermodynamic integration approach. The structure of the mutant enzyme substrate complex obtained from free energy simulation is in good agreement with experimental X-ray refinement. The near perfect reversibility is obtained in the present work for ensuring the correctness of the free energy calculations. The results of the binding free energy difference are close to similar experimental data. PMID- 8451241 TI - The role of local tight packing of hydrophobic groups in beta-structure. AB - An analysis of the tendency of hydrophobic groups to tight packing on the surface of beta-sheets based on well-known parameters of beta-sheets and hydrophobic groups was conducted. This analysis shows the existence of very limited numbers and clearly outlined architecture families of regular parts for the majority of beta-structure-containing domains. Each family of architecture strongly depends on the number of beta-strands in the pure beta-domains and on the existence and number of additional alpha-helixes and on the mutual arrangements beta-strands and alpha-helixes along the chain in mixed alpha/beta-domains. This paper demonstrates that the tendency of hydrophobic groups to the local tight packing on the surface of beta-sheets is probably the main reason for the twist of beta sheets. PMID- 8451242 TI - Crystallographic analysis of Thr-200-->His human carbonic anhydrase II and its complex with the substrate, HCO3-. AB - A complex of carbonic anhydrase (CA) with one of its substrates, bicarbonate, has been studied crystallographically. Human isoenzyme II was mutated at position 200 from threonine to histidine, which results in higher affinity for bicarbonate. The HCO3- ion binds in the active site to the zinc ion as a pseudo-bidentate ligand which gives the metal a coordination geometry between tetrahedral and trigonal bipyramide. The water/hydroxide normally bound with tetrahedral coordination to the zinc is probably replaced by the OH group of the bicarbonate ion. The importance of residues Thr-199 and Glu-106 in controlling the binding orientation of HCO3- is discussed as well as the catalytic mechanism. Both the complex as well as the uncomplexed mutant were studied at 1.9 A resolution. PMID- 8451243 TI - Studies of the zein-like alpha-prolamins based on an analysis of amino acid sequences: implications for their evolution and three-dimensional structure. AB - alpha-Prolamins are the major seed storage proteins of species of the grass tribe Andropogonea. They are unusually rich in glutamine, proline, alanine, and leucine residues and their sequences show a series of tandem repeats presumed to be the result of multiple intragenic duplication. Two new sequences of alpha-prolamin clones from Coix (pBCX25.12 and pBCX25.10) are compared with similar clones from maize and Sorghum in order to investigate evolutionary relationships between the repeat motifs and to propose a schematic model for their three-dimensional structure based on hydrophobic membrane-helix propensities and helical "wheels." A scheme is proposed for the most recent events in the evolution of the central part of the molecule (repeats 3 to 8) which involves two partial intragenic duplications and in which contemporary odd-numbered and even-numbered repeats arise from common ancestors, respectively. Each pair of repeats is proposed to form an antiparallel alpha-helical hairpin and that the helices of the molecule as a whole are arranged on a hexagonal net. The majority of helices show six faces of alternating hydrophobic and polar residues, which give rise to intersticial holes around each helix which alternate in chemical character. The model is consistent with proteins which contain different numbers of repeats, with oligomerization and with the dense packaging of alpha-prolamins within the protein body of the seed endosperm. PMID- 8451244 TI - Systematic care brings results. PMID- 8451245 TI - How necessary is cardiac rehabilitation? Assessment of post-MI patients receiving limited rehabilitation. AB - This study was undertaken to assess the level of knowledge, profile of mood, and activities of daily living among post-myocardial infarction patients at a hospital with only a limited cardiac rehabilitation service. Its findings suggest such programmes are extremely beneficial to patients. PMID- 8451246 TI - Learning that adds to your professional development. Academic accreditation of Professional Nurse Study Days. AB - Keeping up-to-date with clinical practice and ensuring practice is research-based are vital to nursing. A joint initiative between Professional Nurse and Queen Charlotte's College means delegates to Professional Nurse Study Days and Seminars can gain credits to contribute to academic study programmes. PMID- 8451247 TI - Avoiding an unnecessary outcome. A comparative trial between IV3000 and a conventional film dressing to assess rates of catheter-related sepsis. AB - A new transparent dressing, IV3000 is reported to be successful in preventing moisture accumulation around the catheter site. A trial was thus undertaken to compare its effectiveness in preventing catheter-related sepsis with a conventional film dressing. PMID- 8451248 TI - Clinical trials with budgetary implications. Establishing randomised trials of pressure-relieving aids. AB - It is essential that decisions about purchasing pressure-relieving products are made with reference to the results of clinical trials. This article, the first in a four-part series, outlines the criteria for choosing pressure-relieving products and sets the scene for a series of randomised, clinical trials of commonly used beds and overlays. PMID- 8451249 TI - Clinical application of lasers. AB - The use of lasers is a rapidly expanding technological discipline. It has advantages for patients, but is not without potential hazards for practitioners and patients. Regular screening should be commonplace among practitioners. Adequate education for nurses working in regular contact with this technology should be seen as a priority. PMID- 8451250 TI - Should we give them responsibility? Healthcare staffs' views on self-medication. AB - Self-medication is a relatively new concept in the UK, but could benefit patients by giving them control over their treatment. This study looks at healthcare professionals' views of the concept. PMID- 8451251 TI - Are they getting enough? Meeting the oxygen therapy needs of postoperative patients. AB - Many patients require oxygen therapy as part of their postoperative care. A study to assess whether patients were actually given the supplementary oxygen prescribed showed many received only intermittent therapy. Placing more emphasis on oxygen therapy in nurse education would do much to improve its use in practice. PMID- 8451253 TI - Endpiece. The language of the emotions. PMID- 8451252 TI - Solid oral dosage forms. AB - The oral route of drug administration is the most convenient for patients, with tablets emerging as the most popular solid oral dosage form used today. Standard compressed, controlled-release and coated tablets are the most common form of solid oral dosages. A wide range and diversity of ingredients are often included in tablet formulations. A knowledge of the difference between tablet and capsule formulations should enable nurses to improve patient compliance with respect to solid oral dosage forms. PMID- 8451254 TI - Genetic selection alters thermoregulatory response to ethanol. AB - The present study examined the effect of ethanol on the regulated temperature of two lines of mice selected in replicate for a smaller (HOT1 and HOT2) or greater (COLD1 and COLD2) decline in rectal temperature after IP ethanol. Mice were implanted with indwelling telemetry devices for remote monitoring of internal temperature and trained in a temperature gradient (8-40 degrees C). Both internal and selected temperature were tracked and recorded with a computer after injections of NaCl or various doses of ethanol. All animals responded similarly to control injections, with a transient rise in body temperature. After an effective dose of ethanol, mice showed clear evidence of a regulated decline in body temperature, as evidenced by selection of low temperatures in the gradient at the same time internal temperatures were falling. COLD mice were more sensitive than HOT mice; this was apparent in both replicates of the selected lines, indicating that a difference in the CNS regulator of body temperature has been selected for in these animals. PMID- 8451255 TI - Cholecystokinin receptors and memory: a radial maze study. AB - CCK receptor agonists and antagonists have repeatedly been demonstrated to improve and impair, respectively, learning and memory functions. However, all studies to date have exploited avoidance paradigms. In the present study, the effect of some CCK receptor agonists and antagonists on the ability to learn an appetitively motivated task and to influence spatial working memory was investigated. In the first experiment, drugs were given immediately after each training session in the radial maze and the animals were tested, drug-free, during a 2-week period. After the initial treatments with caerulein, an unselective CCK receptor agonist (100 ng/kg SC), the animals were slightly less successful to obtain food pellets during the sessions on the first 2 days; whereas proglumide, an unselective CCK receptor antagonist (1 mg/kg SC) was without any effect. However, on the following days, all the three groups of rats (saline, caerulein, and proglumide) performed in a similar way. In the second experiment, drugs were given before each test session to well-trained animals. Scopolamine (0.15 and 0.3 mg/kg IP), the reference amnestic drug, produced dose dependent impairment of working memory in the radial maze test. Proglumide (1 and 10 mg/kg SC) and devazepide, (a selective CCK-A receptor antagonist; 0.01 and 1 mg/kg SC), as well as caerulein (0.01, 0.1 and 1 microgram/kg SC) and CCK-4 (a selective CCK-B receptor agonist; 25 and 50 micrograms/kg SC) had no reliable effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8451256 TI - Attenuated cortisol response to psychological stress but not to CRH or ergometry in young habitual smokers. AB - Salivary cortisol and heart rate responses to a) psychological stress (public speaking and mental arithmetic), b) human corticotropin-releasing hormone (hCRH), and c) bicycle ergometry until exhaustion were investigated in 10 smokers and 10 nonsmokers. Compared to d), an injection of physiological saline, psychological stress as well as hCRH resulted in significant elevations of salivary cortisol levels in the total group. Ergometry workload induced only moderately enhanced cortisol concentrations. Profound changes in heart rates were observed following bicycle ergometry [+83 beats per minure (bpm)] and after the psychological stress (+29 bpm). hCRH injection increased heart rate by 5 bpm while heart rates dropped after saline administration (-2 bpm). Smokers showed an attenuated cortisol response to the psychological stressor. Mean cortisol increases reached only one third in smokers compared to nonsmokers. Similarly, cortisol levels in smokers tended to be lower after hCRH injection; however, this difference was not statistically significant. Cortisol responses to ergometry did not differ between the two groups. Likewise, heart rates did not reveal different profiles in any of the three stimulations in smokers compared to nonsmokers. PMID- 8451257 TI - Effects of ketamine and L-glutamic acid diethyl ester on spatial and nonspatial learning tasks in rats. AB - An NMDA antagonist, ketamine, at the highest dose tested (15 mg/kg), impaired the acquisition of a hole-board spatial learning task but not the acquisition of a left-right alternation task. A non-NMDA (quisqualate) antagonist, L-glutamic acid diethyl ester (LGDE), did not impair the acquisition of either task. Both drugs had effects on different aspects of a go-no go discrimination task and a straight runway task, ketamine tending to activate and LGDE tending to slow rats. These results concur with previous research regarding the sensitivity of some spatial tasks to NMDA antagonism. Non-NMDA antagonists affect behavior without causing spatial deficits. PMID- 8451258 TI - Differences in ethanol-induced behaviors in normal and acatalasemic mice: systematic examination using a biobehavioral approach. AB - In studies designed to further examine the previously reported involvement of catalase in ethanol-induced effects, we attempted to confirm earlier observations by using normal (C3H-N) and acatalasemic (C3H-A) mice. These mice are identical in every respect and differ only in their catalase activity. Data suggested that the application of 3-amino-1,2,4-triazole (AT), a catalase inhibitor, to both substrains of mice resulted in a proportional decrease in motor activity, thus supporting our earlier observations. We also showed that this effect was specific to ethanol because AT did not have any effect on cocaine-induced motor activity in both substrains. Contrary to the effects of ethanol, these substrains did not differ in motor activity in response to cocaine. In an additional study, we observed that acatalasemic mice differed from the normals in their pattern of voluntary ethanol consumption. Acatalasemic mice consumed more ethanol but only when it was presented in the range of concentrations between 12 and 18%. Finally, we also obtained data suggesting that acatalasemic mice have longer duration of sleep time following ethanol administration compared to normals. Catalase activity was measured in both substrains. Results, once again, confirmed earlier data that the substrains differ in this activity and that AT further decreases brain catalase activity in both mice. Finally, when brain homogenates derived from both substrains were incubated with ethanol significant differences in the amount of generated acetaldehyde were found between the two mice strains. Together, these results provide strong support for the involvement of brain catalase in a variety of ethanol-induced behavioral effects. PMID- 8451259 TI - Effects of methylmercury and trimethyltin on cardiac, platelet, and aorta eicosanoid biosynthesis and platelet serotonin release. AB - The effects of two organometals on heart, platelet, and aorta prostaglandin biosynthesis were examined in vitro. Methylmercuric chloride (MMC, 39-796 nM) increased the biosynthesis of thromboxane A2 (TxA2) and prostacyclin (PGI2) in the heart and stimulated the biosynthesis of PGI2 in incubates of aorta rings. The aorta biosynthesis of PGI2 was monitored by its inhibition of platelet aggregation and serotonin [5-hydroxytryptamine (5-HT)] secretion, while the metabolites 6-keto-PGF1a and TxB2 were quantified by radioimmunoassay. In platelet experiments, low concentrations of MMC (5 microM) enhanced aggregation to adenosine diphosphate (ADP) and at high concentrations MMC (50-100 microM) directly stimulated aggregation and 5-HT secretion. These effects of MMC were inhibited by nonsteroidal antiinflammatory drug, thromboxane synthetase, and phospholipase A2 inhibitors. Trimethyltin (TMT), another highly toxic organometal, had no effect on prostaglandin biosynthesis in either heart or aorta incubates. TMT did not increase platelet aggregation responses to ADP, nor did it directly trigger aggregation. At moderate concentrations, TMT (20-45 microM) slightly depressed ADP aggregation; however, this was paradoxically associated with increased 5-HT secretion. In platelets pretreated with either NDGA or ASA, TMT in the absence of aggregation enhanced 5-HT secretion in response to ADP. TMT, unlike MMC, did not stimulate platelet TxB2 biosynthesis from exogenous [3H]arachidonic acid, whereas MMC stimulates heart, vascular, and platelet eicosanoid biosynthesis. TMT, unlike MMC, does not directly activate the arachidonic acid cascade. PMID- 8451260 TI - Coffee consumption, blood pressure tonus and reactivity to physical challenge in 338 women. AB - The relationships of coffee consumption habits and cardiovascular tonus at rest and in response to an orthostatic and an ergometric challenge were determined in 338 nonsmoking women. Habitual coffee consumption was unrelated to blood pressure. Coffee consumption on the test day was associated with slightly higher systolic blood pressure at rest and with smaller increases due to ergometer cycling. The latter was confirmed by a similar relation with saliva caffeine concentrations measured in a subsample (n = 200). These findings are discussed in terms of a transient stabilising effect of caffeine on blood pressure. PMID- 8451261 TI - Anorectic effects of amylin in rats over the life span. AB - Amylin is a pancreatic peptide hormone that has been demonstrated to antagonize a number of the effects of insulin. This study demonstrated that amylin, when administered IP, decreased food intake in 4-month-old rats at doses of 50, 75, and 100 micrograms/kg. Amylin was slightly more potent at suppressing food intake at 13 months of age and less potent at decreasing food intake in 21- and 25-month old rats, but the difference was not significant. These studies show that amylin is another peripheral anorectic peptide. They do not implicate amylin in the pathogenesis of the anorexia of aging. PMID- 8451262 TI - Anticonvulsant activity of flumazenil in rats during ontogenetic development. AB - The influence of flumazenil on seizures induced by pentylenetetrazol (PTZ) was studied in rats aged 7, 12, 18, 25, and 90 days. Flumazenil in doses of 25, 37.5, and 50 mg/kg IP injected 10 min before PTZ exhibited a dose-dependent anticonvulsant action in all age groups studied. It was more effective against generalized tonic-clonic than against minimal clonic seizures at all developmental stages studied. In the two youngest groups, minimal seizures were elicited only rarely under control conditions. Pretreatment with the two lower doses of flumazenil resulted in an increased incidence of this type of seizure for these two groups. The anticonvulsant activity found in all age groups is in agreement with data from other benzodiazepines and speaks against a pure benzodiazepine-antagonistic action of flumazenil. PMID- 8451263 TI - Fenfluramine-induced place aversion in a three-choice apparatus. AB - The hedonic properties of the anorectic agent fenfluramine (0.25, 1.0, 2.5, 5.0, and 10.0 mg/kg) were assessed in two experiments in a place conditioning paradigm. After four conditioning trials, rats were tested for their preference for a drug-paired chamber, saline-paired chamber, and a novel chamber. Fenfluramine produced a place aversion at doses of 2.5-10 mg/kg. PMID- 8451264 TI - Effects of streptozotocin-induced diabetes on dopaminergic functioning in the rat: analysis of yawning behavior. AB - Apomorphine, a dopamine receptor agonist, causes yawning in rats. It has been suggested that the analysis of yawning behavior provides an index of dopamine autoreceptor function. Dopamine turnover in the substantia nigra of diabetic rats has been shown to be decreased following administration of amphetamine or apomorphine (17,21). Yawning behavior after 4 weeks of streptozotocin (STZ) induced diabetes in Wistar rats was significantly lowered when compared with their age-matched normal controls. Yawning behavior was not further diminished after an 8-week duration of diabetes mellitus; however, a significant recovery in yawning was seen by 20 weeks of diabetes. Yawning in rats after 20 weeks of STZ induced diabetes mellitus is not significantly different from that seen in normal control rats. The results suggest that in STZ-induced diabetes of only 4 weeks duration a measurable change in the substrate for yawning has occurred. PMID- 8451265 TI - Ventrolateral striatal dopamine depletions impair feeding and food handling in rats. AB - The present study was conducted to characterize the changes in feeding behavior produced by localized depletion of dopamine (DA) in the nucleus accumbens and subregions of the neostriatum in the rat. Food-deprived rats were given at least 2 weeks of training, which consisted of being placed in a Plexiglas box and being given 15-18 g of food for a 30-min session. After the training period, rats received bilateral injections of the neurotoxic agent 6-hydroxydopamine (6-OHDA) into the nucleus accumbens, ventromedial striatum, or ventrolateral striatum. Observations were made in 30-min tests on days 3 and 7 after surgery, and measures were obtained for total food intake, time spent feeding, rate of feeding, and forepaw usage during feeding. The ventrolateral striatum was the only site at which dopamine depletion altered aspects of food intake. Rats with ventrolateral striatal DA depletion had reductions in food intake, decreases in the rate of feeding, and impaired forepaw usage during feeding. Time spent feeding was not significantly affected by DA depletion. Water consumption was significantly reduced by DA depletions in the ventrolateral striatum but not by depletions at other sites. These results indicate that ventrolateral striatal DA depletions decrease food intake by impairment of motor functions necessary for the performance of feeding behavior. PMID- 8451266 TI - Effect of nonpeptide angiotensin AT-1 and AT-2 antagonists on isoproterenol induced renin release. AB - The AT-1 receptor antagonist, losartan potassium, produced a large rise in plasma renin activity (PRA) after peripheral, but not intracerebroventricular (ICV), administration. Peripheral, but not ICV administration of losartan also augmented the release of renin induced by peripheral administration of the beta-adrenergic agonist, isoproterenol. The increase in PRA induced by losartan plus isoproterenol was greater than the sum of the increases in PRA induced by the individual treatments. There was, however, no significant enhancement of the hypotensive action of isoproterenol by peripherally administered losartan. The AT 2 receptor antagonist, PD 123319, produced no increase in PRA after either peripheral or ICV injection. However, peripheral injection of PD 123319 slightly increased PRA after peripheral administration of isoproterenol. The data are discussed in terms of the relationship between renin-angiotensin systems and fluid intake, with special reference to the failure of peripherally administered losartan to block isoproterenol-induced water intake. PMID- 8451267 TI - The development of morphine-induced antinociception in neonatal rats: a comparison of forepaw, hindpaw, and tail retraction from a thermal stimulus. AB - Two parallel experiments in rats 2-21 days of age investigated the onset and characteristics of morphine-induced antinociception. One measure of reactivity to pain, limb retraction from a hotplate, was utilized for three different limbs (forepaw, hindpaw, and tail) to chart the development of opioid sensitivity. Morphine-induced antinociception, even in 2-day-old rats, was obtained for all limbs, in a dose-related fashion, and reached peak sensitivity at 6-7 days of age. Naltrexone did not affect limb retraction latencies in nonmorphine treated rats at any age. These studies demonstrate early antinociception to low doses of an opiate and establish that the pain system, like positive reinforcement systems, is opiate sensitive. PMID- 8451268 TI - L-tryptophan decreases the breaking point under a progressive ratio schedule of intravenous cocaine reinforcement in the rat. AB - L-Tryptophan (100 mg/kg, IP), the serotonin [5-hydroxytryptamine (5-HT)] amino acid precursor, significantly reduced the mean breaking point maintained under a self-administration progressive ratio schedule of IV cocaine reinforcement (0.6 mg/injection). This effect was produced over the 5 days of self-administration following treatment. Responding maintained under the same progressive ratio schedule for food reinforcement was not affected by L-tryptophan (100 mg/kg, IP). Rats administered L-tryptophan (100 mg/kg, IP) and denied access to cocaine on the day of treatment resumed normal self-administration patterns under a progressive ratio schedule on following test days. This indicates that L tryptophan treatment alone did not induce long-term effects on cocaine self administration. Thus, it would appear that the combination of this 5-HT manipulation and cocaine administration altered the reinforcing efficacy of the drug and induced a long-term decrement in breaking point under a progressive ratio schedule. This may have been due to an associative aversion to cocaine self administration behaviour learned on the day of treatment and carried over to the subsequent 5 days of self-administration access. PMID- 8451269 TI - Differential effects of nicotine but not cathinone on motor activity of P and NP rats. AB - The locomotor stimulatory effects of nicotine (0.4 and 0.8 mg/kg) and cathinone (0.5 and 1.0 mg/kg) were assessed in alcohol-preferring (P) and -nonpreferring (NP) rats. Whereas P rats demonstrated enhanced (0.8 mg/kg) or no change (0.4 mg/kg) in spontaneous locomotor activity (SMA) to nicotine, NP animals showed no change (0.4 mg/kg) or depression of activity (0.8 mg/kg). However, following cathinone administration both P and NP rats exhibited an increase in SMA. The above results are discussed in light of the genotypic variations between P/NP rats and the potential mediation of differential neurotransmitter effects in the two lines. PMID- 8451270 TI - Yohimbine potentiates active defensive responses to threatening stimuli in Swiss Webster mice. AB - Yohimbine HCl, an antagonist at alpha 2-noradrenaline receptors with putative panicogenic effects in human subjects, was administered to Swiss-Webster mice at doses of 0.5, 1.0, and 2.0 mg/kg. Animals were then tested in two defense test batteries. Yohimbine produced increases in flight from an approaching/contacting human and potentiated animals' reactions to dorsal contact. During a 5-min exposure to a cat (separated from the mouse by a wire-mesh screen) and the 15-min period thereafter, yohimbine produced a dose-dependent pattern of changes in defensive behaviors that included increases in locomotion, transits from one segment of the test chamber to another, fore- and hindpaw wall climbing, screen climbing and hanging, and roof pushing. Crouching (relative immobility while in a hunched-back posture) was notably decreased at all doses. During the postcat period, two different response patterns, "high-escape" and "low-escape," characterized in part by high and low frequencies of wall climbing, were observed in cat-exposed groups. In yohimbine-injected mice, the low-escape behavior pattern also included a tendency to avoid the segment of the test chamber closest to the cat compartment. Both patterns differed from the crouching and immobility generally exhibited by vehicle-injected, cat-exposed controls. It was suggested that yohimbine effected these behavioral changes by either potentiating neural mechanisms mediating flight or inhibiting mechanisms mediating freezing. This model may have some utility for the investigation of panicogenic and antipanic compounds and may contribute insights into the etiology of panic disorder. PMID- 8451271 TI - Pharmacological nature of soman-induced hypothermia in mice. AB - The object of the study was to determine the pharmacological nature of pinacolyl methylphosphonofluoridate (soman)-induced hypothermia in mice. This was accomplished by examining the soman hypothermia dose response and the effect of various pharmacological antagonists in comparison to the hypothermia responses of muscarinic and nicotinic cholinergic agonists such as oxotremorine and nicotine and another anticholinesterase, physostigmine. Core temperature in mice was monitored by telemetry. In general, atropine antagonized oxotremorine, physostigmine, and soman hypothermia but not nicotine hypothermia whereas mecamylamine antagonized nicotine hypothermia but not that produced by the other agonists. Soman hypothermia was not affected significantly by various pharmacological antagonists, suggesting that other neurotransmitters were not involved in the expression of soman hypothermia. Soman hypothermia appears to be due to muscarinic receptor stimulation and can be effectively antagonized, but not completely, by the use of atropine. Acetylcholinesterase oxime reactivators, such as HI-6 and toxogonin, were ineffective in antagonizing soman-induced hypothermia and reactivating hypothalamic acetylcholinesterase, whereas HI-6 was effective in reactivating soman-inhibited diaphragm acetylcholinesterase when administered up to 10 min after soman, indicating that aging of the soman inhibited acetylcholinesterase had not occurred. Soman hypothermia appears to be primarily a muscarinic receptor-related event. PMID- 8451272 TI - Effects of folic acid and folinic acid on cognitive and motor behaviors in 20 month-old rats. AB - Old rats had lower plasma concentrations of folates but not of vitamin B12 than young rats. Old rats injected with pharmacological doses of folic acid (5 mg/kg) or folinic acid (2.5 mg/kg) every 2 days for a 32-day period spontaneously alternated above chance levels at the 0-min retention interval whereas old rats injected with placebo did not. Rats injected with folinic acid that had plasma folate concentrations above the median for that group alternated at the 3-min retention interval whereas none of the other subgroups did. These results indicate that supplementation with folinic acid at pharmacological doses may decrease perseverative responding and improve spatial memory in old rats. However, neither vitamin group was improved in motor coordination, grip strength, or spatial learning in a water maze. There was no hyperactivity or loss of body weight following vitamin supplementation. PMID- 8451273 TI - Protective sensitivity changes of the motor cortex due to epileptiform experience of the visual cortex. AB - In awake rats, experiments were performed to study early epileptiform events (interictal spike, myoclonic jerk) in relation to a) the strength of the convulsive stimulus, b) the site of the focus, and c) epileptiform experience. For this reason, Na-penicillin G (PCN) was injected either into the motor or visual cortex and, in a second test 2 weeks thereafter, into the motor cortex in all these rats. The median latencies of both the first interictal potential and jerk were independent of the applied PCN concentration in the range between 16 1,000 IU/0.5 microliter (90.5-113 s, and from 106-196 s, respectively), as well as from the injection site in the visual or motor cortex (potential: 80 vs. 69 s; jerk: 124 vs. 129 s, respectively). After epileptiform experience in the visual cortex, the latencies of the first potential and jerk were significantly (p < 0.05) increased compared to animals with an experience in the motor cortex (first potential: 100 vs. 66 s; first jerk: 159 vs. 116 s, respectively). The results show that a PCN focus in the visual cortex decreases the susceptibility of the motor cortex for the convulsant action of PCN. This means that an autoprotective mechanism is activated whose efficiency depends upon a close linkage between the visual and motor cortex. PMID- 8451274 TI - Cellular and learned tolerances to chlordiazepoxide hypothermia and ataxia. AB - Four groups of rats received chlordiazepoxide (CDP): a) intermittently, experiencing hypothermia and rotarod performance (RR) deficit after test doses (contingency); b) chronically, experiencing hypothermia and RR deficit after test doses; c) intermittently, RR preceding test doses and with protection against hypothermia afforded by exposure to heat lamps (nonexperienced, noncontingency); and d) chronically, RR preceding test doses and with protection against hypothermia. After 36 days of chronic CDP (groups 2 and 4) or vehicle (groups 1 and 3), all groups experienced RR and body temperature (BT) drug deficits after test doses of CDP at the postwithdrawal test. Group 1 but not group 3 was tolerant to peak hypothermia of the drug. Both chronic groups (2 and 4) showed marked tolerance to hypothermia. At the postwithdrawal test, after discontinuing chronic CDP or vehicle for 9 days, only groups 2 and 4 lost drug tolerance to hypothermia. After extinction training (daily testing of RR and BT after injecting vehicle over 9 days), group 2 but not group 4 was again less sensitive to CDP-induced hypothermia at the postextinction test. Regarding CDP-induced RR ataxia, group 1 was more tolerant than group 3 at the postchronic test, while group 4 but not group 2 also showed tolerance to ataxia. At the postwithdrawal test, only group 4 lost tolerance to peak RR ataxic effects of CDP. At the postextinction test, only group 1 lost tolerance for ataxia relative to postchronic test results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8451275 TI - Evaluation of response perseveration of rats in the radial arm maze following reinforcing and nonreinforcing drugs. AB - The behavioral effects of three drugs with high abuse potential (amphetamine, heroin, and nicotine) and two substances with low abuse potential (haloperidol and scopolamine) were evaluated in an eight-arm radial maze. Rats were trained to explore the maze for the food reward. Unlike most radial arm maze paradigms, a food pellet was made available every time the rat entered an arm; thus, no external restrictions were placed upon rats' exploratory pattern. Following 3 days of drug-free training, rats were injected prior to testing with one of the five drugs. Analysis of the sequences of arm entries demonstrated that the variability of the search strategy was significantly decreased by amphetamine, heroin, and nicotine. In contrast, scopolamine and haloperidol either decreased or had no effect on preservation. These data, along with previous data on ethanol and diazepam, lead to the speculation that drugs of abuse may share the common property of reducing behavioral variability. PMID- 8451277 TI - Improved prediction of extracellular and total body water using impedance loci generated by multiple frequency bioelectrical impedance analysis. AB - Bioelectrical impedance analysis (BIA) using a frequency of 50 kHz is an established method of predicting total body water (TBW). However, very little research has been performed to determine whether 50 kHz is the optimum frequency for the prediction of TBW from impedance measurements. This paper analyses a mathematical expression describing the equivalent electrical circuit for biological tissue, and derives a graphical representation of the resistive and reactive components. The nature of the resulting impedance locus was used in the analysis of measured whole-body impedance of 42 rats over a range of frequencies to determine the impedance at the characteristic frequency, Zc, and also the impedance at zero frequency, R0. The standard error associated with the prediction of TBW (determined by isotope dilution) using Zc was 5.9% compared with a standard error of prediction of 10.1% using the established BIA method at 50 kHz on the same data. Predictions of extracellular water (ECW) using the impedance at zero frequency, R0, yielded a standard error of 3.2% compared with standard errors of 4.8% and 4.2% using single frequency BIA measurements at 5 kHz and 1 kHz, respectively. These results demonstrate a significant (P < 0.01) improvement in the prediction of TBW and ECW using multiple frequency bioelectrical impedance analysis (MFBIA). PMID- 8451276 TI - Clozapine and haloperidol in an animal model of sensorimotor gating deficits in schizophrenia. AB - Prepulse inhibition (PPI) of the acoustic startle response is a measure of sensorimotor gating that is impaired in both schizophrenic patients and in rats treated with dopamine agonists. The disruption of PPI by the dopamine agonist apomorphine (APO) is reversed by antipsychotic agents, including the atypical antipsychotic clozapine. Across a range of compounds, the ability of antipsychotics to restore PPI in APO-treated rats correlates significantly with their clinical potency. Since few animal models predict antipsychotic potency for clozapine, we further characterized the effects of clozapine and the typical antipsychotic haloperidol on APO-disrupted and baseline PPI in rats. The APO induced disruption of PPI caused by intense (15 dB over background) prepulses was reversed in a dose-dependent manner by both clozapine and haloperidol. When weak (1-5 dB over background) prepulses were used, clozapine and haloperidol increased baseline PPI in control animals. Both APO-disrupted and baseline PPI may be useful in screening both typical and atypical antipsychotic agents. PMID- 8451278 TI - Magnetic fields and intracellular calcium: effects on lymphocytes exposed to conditions for 'cyclotron resonance'. AB - There are a number of claims in the literature that specific combinations of low level DC and AC magnetic fields can cause biologically significant effects. The combinations of fields required to elicit these responses fulfil the theoretical conditions for classical cyclotron resonance of the selected ion. Because of the biological importance of calcium ions any effects on them are of particular interest, for instance the claimed increase in calcium uptake by electromagnetically exposed lymphocytes. We have measured the intracellular calcium concentration, by means of a sensitive fluorescent probe, during a 60 min exposure of mouse lymphocytes to 'cyclotron resonance' conditions for calcium ions. 'Resonance' conditions at two frequencies (16 Hz and 50 Hz) were tested, with a range of DC field amplitudes used to shift the frequency up to 25% either side of the calculated optimum. Treatment of the lymphocytes with concanavalin A was used as a positive control and caused a significant increase in intracellular calcium concentration. No change in intracellular calcium concentration could be detected when lymphocytes were exposed to 'cyclotron resonance' conditions or to the other magnetic field combinations used. PMID- 8451279 TI - FDTD calculations of the SAR for a dipole closely coupled to the head at 900 MHz and 1.9 GHz. AB - This paper presents finite-different time-domain (FDTD) calculations of the specific absorption rate (SAR) averaged over the mass of the eye, and over 1 g and 100 g of tissue in a realistic model of the head from a closely coupled half wavelength dipole source. The SAR is predicted as a function of the separation between the vertical dipole and the surface of the eye. The feed point of the dipole is on the axis defined by the centre of the eye. Phantoms representing an adult and a one-year-old child have been considered for irradiation at 900 MHz and 1.9 GHz. PMID- 8451280 TI - Mathematical modelling of the human cardiovascular system in the presence of stenosis. AB - This paper reports a theoretical study on the distribution of blood flow in the human cardiovascular system when one or more blood vessels are affected by stenosis. The analysis employs a mathematical model of the entire system based on the finite element method. The arterial-venous network is represented by a large number of interconnected segments in the model. Values for the model parameters are based upon the published data on the physiological and rheological properties of blood. Computational results show how blood flow through various parts of the cardiovascular system is affected by stenosis in different blood vessels. No significant changes in the flow parameters of the cardiovascular system were found to occur when the reduction in the lumen diameter of the stenosed vessels was less than 65%. PMID- 8451281 TI - A real time dual-energy probe for tissue characterization during fluoroscopy. AB - In the past dual-energy techniques have been applied with a variety of detector systems. However, making clinical decisions during a diagnostic x-ray procedure by using dual-energy information has not been possible. This paper looks at the development of a dual-energy probe that permits real time analysis. The technique is based on the local analysis procedure introduced by Speller and co-workers and uses spectral filtering for energy separation. The split-detector probe is optimized using computer models, and the effects of beam hardening and scattered radiation are considered. It is shown that a 0.25 mm CsI/25 mm NaI combination of detector elements with a 0.3 mm Cu filter offers the best performance. Preliminary results using the probe for in vivo analysis of gall stone composition compare well with the more accepted methods of x-ray diffraction and atomic absorption spectroscopy. The two groups of stones evaluated were found to have mean effective atomic numbers of 5.6 +/- 1.7 and 9.6 +/- 0.5. It is suggested that such a procedure could prove useful in patient management in the use of lithotripsy. PMID- 8451282 TI - An enhanced sensitivity K-shell x-ray fluorescence technique for tibial lead determination. AB - A novel irradiation-detection geometry capable of enhancing sensitivity for the measurement of tibial lead content by K-shell x-ray fluorescence (XRF) is described. The high-count-rate system comprised a small-area high-specific activity (0.147 GBq mm-2) 109Cd source and a large-area (nominally 20 cm2) uncollimated detector, forming an axially symmetric back-scattering arrangement. Precisions in the range +/- 4.9 to +/- 14.2 micrograms Pb (g bone mineral)-1 have been obtained in a study of a cohort of 63 controls and 73 workers industrially exposed to lead. These precisions are comparable with those obtained in results using earlier systems, but at reduced source activities (less than 50% of the activity of other systems) and with significant reduction in measurement time (some 30% less than the measurement times of other systems). Subsequent investigation of detector collimation resulted in a marginal improvement in energy resolution, but the restriction in detected photon fluence meant that there was an insignificant change in detection sensitivity. For the resistive feedback preamplifier used in this study a maximum energy rate of the order of 7000 MeV s-1 was found to limit measurement precisions significantly. Higher count-rate detector systems offer a basis for obtaining mean precisions down to +/- 3 micrograms Pb (g bone mineral)-1 at one standard deviation. PMID- 8451283 TI - Monte Carlo calculation of dose enhancement by neutron capture of 10B in fast neutron therapy. AB - Since 1978 the Essen Medical Cyclotron Facility has been used for fast neutron therapy. The treatment of deep-seated tumours by d(14) + Be neutron beam therapy (mean energy = 5.8 MeV) is still limited because of the steep decrease in depth dose distribution. The interactions of fast neutrons in tissue leads to a thermal neutron distribution. These partially thermalized neutrons can be used to produce neutron capture reactions with 10B. Thus incorporation of 10B in tumours treated with fast neutrons will increase the relative local tumour dose due to the reaction 10B (n, alpha) 7Li. The magnitude of dose enhancement by 10B depends on the distribution of the thermal neutron fluence, 10B concentration, field size of the neutron beam, beam energy and the specific phantom geometry. The slowing down of the fast neutrons, resulting in a thermal neutron distribution in a phantom, has been computed using a Monte Carlo model. This model, which includes a deep seated tumour, was experimentally verified by measurements of the thermal neutron fluence rate in a phantom using neutron activation of gold foil. When non boronated water phantoms were irradiated with a total dose of 1 Gy at a depth of 6 cm, the thermal fluencies at this depth were found to be 2 x 10(10) cm-2. The absorbed dose in a tumour with 100 ppm 10B, at the same depth, was enhanced by 15%. PMID- 8451284 TI - A cine-SPAMM sequence for NMR imaging of pulsatile cerebrospinal fluid flow. AB - The technical difficulties in designing a SPAMM sequence to image pulsatile cerebrospinal fluid (CSF) flow at different phases of the cardiac cycle are described. The criteria used to select the most appropriate order of binomial SPAMM sequence are outlined. Data collection times required to view both cephalad and caudad flow for all R-R intervals were considered. The flip angles of the RF pulses required to produce images with equal CSF intensity throughout the cardiac cycle were investigated in detail. PMID- 8451285 TI - New phthalocyanine photosensitizers for photodynamic therapy. AB - Six new aluminum and silicon phthalocyanines have been synthesized and their photocytotoxicity toward V79 cells has been studied. The compounds that have been prepared are: A1PcOSi(CH3)2(CH2)3N(CH3)2, I; A1Pc-OSi(CH3)2(CH2)3N(CH3)3+I-, II; CH3SiPcOSi(CH3)2(CH2)3N(CH3)2, III; HOSiPcOSi(CH3)2(CH2)3N(CH3)2, IV; HOSiPcOSi(CH3)2(CH2)3N(CH3)3+I-, V; and SiPc[OSi(CH3)2(CH2)3N(CH3)3+I-]2, VI. Relative growth delay values for compounds I-VI and relative cytotoxicity values for compounds I, II, IV, V and VI have been determined. Compounds I and II have been shown to be comparable in photocytotoxicity to what is presumed to be A1PcOH.xH2O, and compound IV has been shown to have greater activity. The classes of compounds to which these six compounds belong appear to have potential for photodynamic therapy. PMID- 8451286 TI - Direct exposure of mammalian cells to pure exogenous singlet oxygen (1 delta gO2). AB - Mammalian cells attached to membrane filters or deposited on filters without attachment were exposed to gas-phase singlet oxygen (1O2) in the absence of any other reactants. Cells were exposed in a monolayer or less, in the absence of external medium, during steady-state 1O2 generation, ensuring that singlet oxygen impinged directly and equally on all cells simultaneously. The current methodology for cell exposure ensures that 1O2 is initially the only reactive species to which the cells are exposed. Results seen with this system can therefore be attributed solely and unambiguously to events initiated by 1O2. Further, all cells in the sample receive the same magnitude of exposure per surface area per time interval, which supports calculations of the amount of 1O2 required for irreversible cell damage, based on measured 1O2 flux and exposed cell surface area. Exposure to pure 1O2 irreversibly damaged a variety of cell types, including rat basophilic leukemia, human squamous carcinoma and Chinese hamster lung fibroblast cell lines, and murine primary hepatocytes. Cell survival curves following exposure to 1O2 followed apparent first-order kinetics. A large number of singlet oxygen collisions (approximately 10(12)-10(13) were required to inactivate a cell, on average, indicating a low probability that singlet oxygen collision will reduce cell survival. Regardless of cell type or the survival endpoint measured, lethal toxicity required a fairly constant number of 1O2 collisions per cell. This poses a serious caveat in the assignment of causality in correlating 1O2-initiated cellular damage with mechanism of death, i.e. most damage observed will not be related to death.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8451287 TI - A 5-4 pyrimidine-pyrimidone photoproduct produced from mixtures of thymine and 4 thiouridine irradiated with 334 nm light. AB - The nucleoside 4-thiouridine, present in some bacterial tRNA species, is known to be a chromophore and a target for near-UV light-induced growth delay and also mediates both photoprotection and near-UV cell killing in various bacterial strains. To investigate the photoreaction of 4-thiouridine with DNA or its precursors, we irradiated aqueous mixtures of thymine and 4-thiouridine with 334 nm light and then separated photoproducts using two or more stages of reversed phase high performance liquid chromatography. The two equally abundant major photoproducts were analyzed by UV absorbance spectrophotometry, fast-atom bombardment and electron-impact mass spectrometry, and 1H- and 13C-NMR spectroscopy, and have been identified as two diastereomers of 6-hydroxy-5-[1 (beta-D-erythro-pentofuranosyl)-4'-pyrimidin-2'- one]dihydrothymine (O6hThy[5 4]Pdo), of molecular weight = 370.32. These two diastereomers, although stable at room temperature or below, are interconvertible by heating (90 degrees C for 5 min) in aqueous solution. The possible biological significance of this photoproduct is discussed, and an application as a crosslinker for oligonucleotides to selectively block replication is suggested. PMID- 8451288 TI - Effect of UV irradiation on lethal infection of mice with Candida albicans. AB - Exposure of mice to UV radiation inhibits the induction and elicitation of the delayed-type hypersensitivity (DTH) response to Candida albicans. To determine whether UV irradiation also affects the pathogenesis of systemic C. albicans infection, C3H mice were exposed to a single dose of 48 kJ/m2 UV-B radiation from FS40 sunlamps 5 days before or 5 days after sensitization with formalin-fixed C. albicans and challenged intravenously (i.v.) with a lethal dose of viable fungi 6 days after sensitization (11 or 1 days after UV irradiation). Exposing unsensitized mice to UV radiation 11 days before lethal challenge had no effect on survival, but the survival time of mice exposed to UV radiation 1 day before challenge was reduced by more than 50%. In the latter group, decreased survival time correlated with persistence of C. albicans in the brain and progressive growth of C. albicans in the kidneys. Sensitization of unirradiated mice with formalin-fixed C. albicans extended their survival time following lethal i.v. challenge with viable C. albicans. Exposing the mice to UV radiation 5 days before sensitization did not abrogate this beneficial effect of sensitization on survival, even though it significantly reduced the DTH response. Thus, immunity to systemic infection did not depend on the ability of the mice to exhibit a DTH response to C. albicans. The beneficial effect of sensitization on survival after lethal infection was abrogated, however, in mice exposed to UV radiation 1 day before lethal challenge with C. albicans. Furthermore, these mice were unable to contain the progressive growth of C. albicans in the kidneys, in contrast to sensitized, unirradiated mice. PMID- 8451289 TI - Attempted biostimulation of division in Saccharomyces cerevisiae using red coherent light. AB - Replicate cultures of the yeast Saccharomyces cerevisiae were irradiated with 632.8 nm coherent light from He-Ne lasers at irradiances of 6.5 x 10(15) and 1.0 x 10(16) photons s-1 cm-2. Irradiation periods ranged from 0 to 652 min, and cultures were grown until well into the exponential phase. Unirradiated control cultures were grown alongside the irradiated cultures under otherwise identical conditions. The extents of growth in the control and irradiated cultures were compared spectrophotometrically at the end of each experiment. Contrary to the expectations of Karu et al. (e.g. Karu, 1988, Lasers Life Sci. 2, 53-74) no growth enhancement was found in the irradiated cultures, but a mild inhibitory effect was observed. PMID- 8451290 TI - Development of an in vitro system for the analysis of ultraviolet radiation induced suppression of natural killer cell activity. AB - Previous studies have shown that natural killer (NK) cell activity was suppressed in volunteer subjects exposed to ultraviolet radiation (UVR) from solarium lamps. The present studies were carried out to determine the spectrum of UVR responsible for suppression of NK activity and to develop in vitro methods to analyze the effectiveness of sunscreen agents in prevention of UVR-mediated suppression of NK activity and other aspects of immune function. UVR from a xenon arc lamp source was used to irradiate peripheral blood lymphocytes (PBL) in wells of tissue culture flasks, and transmission interference filters were used to eliminate UVR of particular wavelengths. The results indicated that UVR from this source inhibited NK activity of PBL in a dose-dependent manner with a 50% inhibitory dose of 5.5 mJ/cm2 when unfiltered and 29.6 mJ/cm2 when diluted through cellulose acetate, which gave a UV spectrum similar to that in solar radiation. Equivalent suppression of NK activity was mediated by UV-A (UVR > 315 nm) at dose levels of 4.2 J/cm2, which was approximately 140 times greater than the amount of UV-B (UVR < 315 nm) needed to suppress NK activity. Similar dose-response curves were seen for inhibition of mitogenic responses to phytohemagglutinin except that the latter appeared less sensitive than NK to inhibition by UV-A. These studies suggest that when the greater proportion of UV-A in solar radiation and its greater penetration into skin is taken into account, UV-A may have equivalent or greater direct immunosuppressive effects than UV-B.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8451291 TI - Modulation of interferon-gamma-induced HLA-DR expression on the human keratinocyte cell line SCC-13 by ultraviolet radiation. AB - Cell surface expression of major histocompatibility determinants on epidermal keratinocytes is a characteristic feature of a number of inflammatory dermatoses and in all likelihood is caused by diffusion of human leukocyte antigen (HLA)-DR inducing cytokines from cells present in the dermal mononuclear cell infiltrate. Many of these same disorders respond to ultraviolet (UV) radiation phototherapy. Using the human SCC-13 keratinocyte cell line as a model, UV radiation was found to inhibit interferon-gamma-induced HLA-DR expression. Inhibition correlated closely with decreased steady-state levels of HLA-DR mRNA. These findings provide evidence that the therapeutic effect of UV radiation phototherapy may be mediated by its capacity to down-regulate cytokine-induced keratinocyte HLA-DR expression. PMID- 8451292 TI - Effective photodynamic action by rhodamine 123 leading to photosensitized killing of Chinese hamster ovary cells in tissue culture and a proposed mechanism. AB - The effectiveness of rhodamine 123 (R123) as a photosensitizer of cell killing is relatively low and correlates with its inefficient production of singlet oxygen. The known selective retention of R123 in the mitochondria of epithelially derived carcinoma cells, however, is a selective feature that could lead to a more useful therapeutic ratio if photosensitizing effectiveness could be increased. Chinese hamster ovary (CHO) cells in tissue culture were therefore exposed to R123 shortly before and during illumination under conditions controlled for oxygen concentration and temperature. Effective photosensitization of cell killing, as judged by colony formation, was produced by 95% but not by 19% O2 during illumination of cells at 5 degrees C or 37 degrees C, and this was additionally enhanced at the sublethal temperature of 42 degrees C. Two CHO cell lines were examined; one line, CHO-AA8, was proficient in the repair of DNA damage and the parent to the second line, CHO-EM9, that was deficient in the repair of DNA strand breaks. Cells of both lines incorporated R123 to a similar degree and were similarly photosensitized by the presence of high oxygen concentration. Furthermore, plasma membrane damage as judged by the exclusion of trypan blue was not observed immediately after illumination in the presence of R123, but was seen in the presence of meso-tetra-(4-sulfonatophenyl)-porphine (TPPS4). The extent of damage to the plasma membrane by TPPS4 was greater in the presence of 95% compared to 19% O2 during illumination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8451293 TI - The role of lipoproteins in the distribution of tin etiopurpurin (SnET2) in the tumor-bearing rat. AB - The role of plasma lipoproteins in the distribution of the photosensitizing agent tin etiopurpurin (SnET2) was examined in male rats bearing the N-[4-(5-nitro-2 furyl)-2- thiazolyl1bdformamide-induced tumor. Treatment with 17 alpha-ethinyl estradiol resulted in the depletion of total plasma cholesterol by > 70% and a corresponding decrease in plasma lipoproteins. To both control and estradiol treated animals, a therapeutic dose (1.5 mg/kg) of SnET2 was administered and biodistribution measured 24 h later. Estradiol treatment was not associated with differences in the distribution of SnET2 to liver, skin or tumor, or in the pattern of affinity of SnET2 to plasma albumin and lipoprotein. These results indicate that a substantial decrease in circulating lipoprotein levels does not alter patterns of SnET2 biodistribution. PMID- 8451295 TI - Optical properties of experimental prostate tumors in vivo. AB - The optical properties of tumor tissue provide important information for optimizing treatment plans in photodynamic therapy, especially when interstitial application by multiple fibers is planned. Near infrared light, required to activate novel photosensitizers, should facilitate improved light penetrance of tumor tissue compared with 630 nm light used for activating Photofrin II. We have measured light energy fluence rates for 630 and 789 nm light along radial tracks from a single laterally diffusing optical fiber centrally implanted into Dunning R3327-AT and R3327-H rat prostate tumors in anesthetized rats. A total of 20 R3327-AT and 10 R3327-H tumors were used in this study with volumes from 2.6 to 13.3 cm3. Light track data were analyzed by an empirical model that described light attenuation. At 630 nm, light attenuation coefficients (LAC) were approximately 1.9 x higher than those at 789 nm for both tumors with the well differentiated, well-perfused tumor (R3327-H) attenuating to a greater extent than did the rapidly growing anaplastic tumor (R3327-AT). The intertumor variation of LAC was greater than the spatial variations observed within individual tumors. LAC were a function of tumor volume for only 630 nm light in the R3327-AT tumors. PMID- 8451294 TI - Exposure to long wavelength ultraviolet radiation decreases processing of low density lipoprotein by cultured human fibroblasts. AB - Exposure of MRC5 human fibroblasts to UVA radiation (365 nm) resulted in a dose dependent decrease in low density lipoprotein (LDL) uptake and degradation by cells. Following a 25 J/cm2 irradiation dose, about 45% and 70% reduction in 125I LDL uptake and degradation were observed, respectively. Under the same conditions, the 14C-sucrose uptake was also decreased to about the same extent as LDL uptake. Cell pretreatment with the antioxidants vitamin E and vitamin C did not prevent the UVA-induced fall in LDL degradation. These results point to the possible effects of UVA radiation on receptor-mediated and nonspecific uptake of exogenous molecules. With special regard to the alterations in receptor-mediated processing of exogenous ligands, such a phenomenon could be of importance in UVA induced skin degenerative processes. PMID- 8451296 TI - Concentration dependence of transmission losses in UV-laser irradiated bovine alpha-, beta H-, beta L- and gamma-crystallin solutions. AB - Experiments with calf lens protein fractions in aqueous buffer solutions at room temperature showed that beta H-, beta L- and gamma-crystallin fractions became opaque following ultraviolet exposure at 308 nm, while the alpha-crystallin fraction remained transparent. Transmission loss, due to UV-irradiation, for all of the crystallin samples was studied in the concentration range of 0.1 mg/mL to 1.0 mg/mL, and for alpha- and gamma-crystallin, in the range up to 5 mg/mL. With increased concentrations of beta H-, beta L- and gamma-crystallin, the rate of opacification increased. However, with alpha-crystallin, the loss of transmission was negligible for all of the concentrations and irradiation times studied. Opacification of the crystallins was accompanied by formation of higher molecular weight insoluble proteins as detected by SDS-PAGE. PMID- 8451297 TI - Gene expression of the B875 light-harvesting prepolypeptides from Rhodospirillum rubrum in Escherichia coli. AB - The gene coding for the prepolypeptides of alpha and beta, obtained as a 429 bp fragment from chromosomal DNA of Rhodospirillum rubrum S1 by polymerase chain reaction amplification, were cloned in tandem into the high-level expression vector pOTSNco 12 for expression in Escherichia coli. The vector pOTSNco12 is a derivative of the pAS vector system, which contains the strong lambda PL promotor and is under tight control by the cI857 repressor encoded by the expression strain AR58. Induction of transcription from the lambda PL promotor is achieved by shifting the growth temperature from 32 to 42 degrees C. Expression of the gene products was monitored by sodium dodecylsulfate polyacrylamide gel electrophoresis and western blotting. The expressed B875 light-harvesting prepolypeptides were located in the E. coli inner membrane and could not be removed by washing with high salt. The amount of expressed B875 light-harvesting prepolypeptides was estimated to be about 0.1% of the total soluble protein. PMID- 8451298 TI - The peroxidative metabolism of tenoxicam produces excited species. AB - The peroxidative metabolism of the nonsteroid anti-inflammatory oxicams generates metabolites of the type expected from a dioxetane intermediate. Therefore, electronically excited metabolites may be expected. Consistent with this possibility, both direct and sensitized light emission are observed when tenoxicam is exposed to horseradish peroxidase or when added to leukocytes, where it undergoes a myeloperoxidase-catalyzed aerobic oxidation. The similarity between peroxidative metabolism with concomitant oxygen uptake and photodegradation brought about by singlet oxygen addition to the substrate is pointed out. As a whole, the results strengthen the view that electronically excited species should also be considered when analyzing the effect(s) of xenobiotics. PMID- 8451299 TI - Phosphorescence lifetime studies of interactions between serum albumins and sodium dodecyl sulfate. AB - Binding of sodium dodecyl sulfate (SDS) to bovine serum albumin (BSA) and human serum albumin (HSA) in aqueous solutions at room temperature induces significant changes in the phosphorescence lifetime of tryptophan (Trp) residues. A steep rise of the phosphorescence lifetime from 1.9 ms to 10.0 ms for BSA and from 1.9 ms to 5.5 ms for HSA is observed when the total SDS concentration increases from 0.0 mM to 0.22 mM at 1 mg/mL protein concentration. As the total SDS concentration is further increased to 2.2 mM, a slower increase in the phosphorescence lifetime is observed, from 10.0 ms to 19.5 ms for BSA and from 5.5 ms to 7.2 ms for HSA. It appears that the phosphorescence lifetime modifications are mainly due to an increase of protein matrix rigidity around Trp residues. The observed differences (between HSA and BSA) allow us to distinguish the contribution of the two Trp residues to the BSA phosphorescence. PMID- 8451300 TI - Lovastatin potentiates the photocytotoxic effect of photofrin II delivered to HT29 human colonic adenocarcinoma cells by low density lipoprotein. AB - A 24 h preculture of HT29-18 human colonic adenocarcinoma cells with the sterol synthesis inhibitor lovastatin at concentrations of 0.1-0.5 microM markedly increased the photocytotoxic effect of photofrin II delivered to cells by low density lipoproteins. Under the same conditions, LDL binding and photofrin II (PII) uptake by HT29 cells increased about 1.8-fold and 1.5-fold, respectively. These results suggest that hydroxymethylglutaryl-coenzyme A reductase inhibitors could be useful for potentiating the photodynamic therapy of tumors by PII. PMID- 8451301 TI - Hydrogen peroxide-dependent generation of singlet molecular oxygen by human saliva: its detection by chemiluminescence from a Cypridina luciferin analog. AB - By the addition of hydrogen peroxide to human saliva, chemiluminescence from Cypridina luciferin analog (CCLA) and oxygen evolution were observed. Chemiluminescence was inhibited by inhibitors of salivary peroxidase, azide and cyanide and by a singlet oxygen quencher, crocin. Deuterium oxide (99.75%) stimulated the initial increase of CCLA by 15-50% and the integrated CCLA 2.1-3.6 fold. The results suggest that the generation of singlet oxygen by peroxidase in human saliva depends on hydrogen peroxide. PMID- 8451302 TI - Ultraviolet radiation-induced phospholipase A2 activation occurs in mammalian cell membrane preparations. AB - Ultraviolet erythema in human skin is mediated in part by membrane derivatives of arachidonic acid (AA). UVA (320-400 nm) and UVB (290-320 nm) have been shown to induce release of AA from intact mammalian cells in culture. In order to investigate the mechanism of this release we examined the effect of UVA and UVB on release of [3H] AA from membrane preparations of murine fibroblasts. C3H 10T1/2 cells were prelabelled for 24 h with [3H] AA. The membrane fractions of the cells were separated after lysis by differential centrifugation. The membranes were irradiated in suspension and the [3H] AA released from the membranes was determined by scintillation spectroscopy of supernatants 3-4 h after irradiation. Both UVA and UVB induced release of AA from the membrane preparations. The response to UVB was small but significant, reaching levels approximately 150% of control release at doses of 1,200-4,000 J/m2. The response to UVA was larger; doses of 2.5-5.0 J/cm2 induced release equal to twice control (200%) levels, while doses of 10-20 J/cm2 induced maximal release at levels approximately 400% of control. Time course studies with UVB and UVA showed maximal release at 4 h after irradiation. When the membrane preparations were incubated with a polyclonal anti-phospholipase A2 antibody the UV induced release of [3H] AA was completely inhibited in both UVB (1200 J/m2) and UVA (10 J/cm2) treated cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8451303 TI - Fluorescent polyene aliphatics as spectroscopic and mechanistic probes for bacterial luciferase: evidence against carbonyl product from aldehyde as the primary excited species. AB - The fluorescent alpha-parinaric acid (alpha-PAC) and beta-parinaric acid (beta PAC) were converted to the corresponding aldehydes and alcohols all of which exhibited absorption and fluorescence properties closely resembling those of the parent acids. alpha-PAC and beta-PAC each binds to luciferase in competition with aldehyde. The hydrophobic nature of the aldehyde site was indicated by the enhanced fluorescence quantum yields of the bound alpha-PAC and beta-PAC. These two polyene acids and the beta-parinaryl alcohol were shown to stabilize the luciferase flavin-peroxide intermediate. alpha-Parinaraldehyde (alpha-PAD) and beta-parainaraldehyde (beta-PAD) were active substrates for Vibrio harveyi and Vibrio fischeri luciferases and, for the former enzyme, exhibited Km values similar to and quantum yields about 20-30% as those for decanal and dodecanal. For the V. harveyi luciferase with reduced FMN as a co-substrate, the alpha-PAD- or beta-PAD-initiated luminescence was indistinguishable from the normal emission obtained with octanal (lambda max 495 nm) showing no additional 430-nm component correlatable with emission from excited alpha-PAC or beta-PAC. In reactions using reduced 2-thioFMN for V. harveyi luciferase or reduced FMN for V. fischeri luciferase plus yellow fluorescent protein, the replacement of octanal by beta PAD again resulted in no additional 430-nm emission. The lack of any emission correlatable with excited alpha-PAC, beta-PAC, or equivalent carbonyl product was not due to the quenching of the polyene moiety by chemical transformation, binding to luciferase, or a 100% energy transfer to the flavin 4a-hydroxide emitter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8451304 TI - Women in Physiology Mentoring Program. PMID- 8451305 TI - Effect of meal pattern during food restriction on body weight loss and recovery after refeeding. AB - The present study was designed to assess whether the pattern of meal feeding and the degree of caloric restriction have an effect on the body weights and refeeding patterns of restricted 4-month-old Long-Evans rats, relative to ad lib fed controls. Four experimental groups of rats (n = 6 each) were put on different paradigms of food restriction, and a fifth group fed ad lib throughout served as controls. Twelve rats were restricted to receiving 50% of their mean baseline food intake, and 12 rats received only 70% of their baseline food intake. Each experimental group was further subdivided with one subgroup receiving all of their calories in one meal/day and the other with caloric intake equally divided into two meals/day. There was no statistical difference in the final body weights of the restricted groups. Although there appeared to be identical patterns of weight regain, none of the restricted groups ever reached the mean body weight of the controls because of an asymptotic leveling off of rate of body weight regain. Rats that had received 50% of baseline calories as two meals/day had significantly more adipose mass than did any other group. The present findings suggest that in the rat, refeeding and, hence, regulation, occurs to normalize rate of weight gain rather than absolute body weight. PMID- 8451306 TI - Surgical removal of the pregastric pouch reduces voluntary lactose consumption in golden hamsters. AB - Unlike other adult mammals, golden hamsters voluntarily consume substantial amounts of the disaccharide sugar lactose. It was hypothesized that the hamster's readiness to consume lactose depends upon its possession of a pregastric pouch in which ingested lactose is broken down into its constituent monosaccharides, thus preventing the aversive gastrointestinal symptoms that monogastric animals experience following lactose ingestion. Adult golden hamsters underwent either surgical removal of the pregastric pouch or sham surgery. Following recovery from surgery, hamsters were given continuous free access for 14 days to tap water, Purina Rodent Chow, a 24% sugar solution (either lactose or sucrose), and a Purina chow-based diet containing 30% added sugar (for each hamster, the same sugar that was provided in solution). Surgical removal of the pregastric pouch caused a 40% reduction in total lactose consumption: this reduction resulted from equivalent decreases in consumption of the lactose solution and the lactose containing diet. Pouch removal had no effect on total sucrose consumption, and sham surgery had no effect on either lactose or sucrose consumption. These results support the conclusion that the adult hamster's unusually high level of voluntary lactose consumption depends upon its possession of a pregastric pouch, which plays an important role in lactose digestion. PMID- 8451307 TI - Nonphotically induced phase shifts of circadian rhythms in the golden hamster: activity-response curves at different ambient temperatures. AB - Running in a novel wheel during the subjective day can shift the circadian activity rhythm of a hamster. The amount of running is thought to be an important variable. We generated a dose-response (activity-phase shift) curve for the amount of wheel running during a 3 h period starting 8 h before normal dark onset in a 14:10 LD cycle. At room temperature (23 degrees C) the relationship was sigmoidal: from 0 to 4000 revolutions resulted in minimal phase advances (up to 50 min). From 4000 to 5000 revolutions the magnitude of the advances increased sharply, and above 5000 revolutions phase advances were asymptotic at about 3 h. The same general relationship held when hamsters were stimulated to be more active in the novel wheel by lowering the ambient temperature to either 11 degrees C or 6 degrees C. However, at these lower temperatures, a significant number of animals did not shift more than the minimal amount of 50 min even though they ran more than 5000 revolutions. This indicates that running per se in a novel wheel was not sufficient to induce phase shifts. Possibly, at room temperature, the amount of wheel running reflects a particular motivational state produced by the rewarding nature of wheel running, although at low ambient temperatures at least some individuals run primarily to meet thermoregulatory needs. PMID- 8451308 TI - The effect of prenatal stress on adult sexual behavior in rats depends on the nature of the stressor. AB - It is well known that prenatal stress induces behavioral demasculinization and/or feminization in male offspring during adulthood. In this study, four different stressors were prenatally applied to rats. Pregnant rats were subjected to immobilization, unavoidable electric foot shocks, rapid eye movement sleep deprivation (REMd), or immersion in cold water. During adulthood, male offspring were tested for masculine and feminine sexual behavior. The results corroborated the fact that immobilization induced an impairment of masculine sexual behavior and a facilitation of feminine sexual behavior. Electric shocks showed only minor differences in masculine behavior when compared to intact controls, and no signs of lordosis behavior were observed. The REMd group displayed a major impairment of masculine behavior, even greater than that observed within the immobilization group. However, lordosis behavior was only induced with estradiol. On the other hand, water immersion seems to have a facilitatory effect on several parameters of masculine behavior and did not show lordosis behavior even with hormonal treatment. These results strongly suggest that changes in sex behavior induced by prenatal stress are linked to the nature of the stressor. PMID- 8451309 TI - Negative affect, absorption, and immunity. AB - Relationships between the psychological characteristics absorption and neuroticism, and in vitro and in vivo measures of cell-mediated immunity were examined. Thirty-nine female subjects responded to questionnaires, donated blood for analysis of T-cell numbers, and were tested for delayed hypersensitivity skin responses. Consistent with the experimental hypothesis, subjects classified as repressors of negative affect (low absorption/low neuroticism), or extreme expressors of negative affect (high absorption/high neuroticism), showed lower immune responses than other groups of subjects. For the in vitro T-cell measures and the in vivo skin induration measures, there were also pervasive main effects of neuroticism, with subjects higher in neuroticism showing higher immunity than subjects lower in neuroticism. PMID- 8451310 TI - Consuming aspartame with and without taste: differential effects on appetite and food intake of young adult males. AB - Despite some reports that aspartame (APM)-sweetened beverages may increase subjective appetite, previously we demonstrated that drinking 280 ml of an APM sweetened soft drink (170 mg APM) had no effect on appetite, and 560 ml of the same soft drink (340 mg APM) reduced appetite. The present study examined this appetite reduction to determine its cause. Eighteen normal weight young adult males received five treatments (beverage preloads) at 1100 h in a randomized order, one per week: 280 ml of carbonated mineral water (CMW) (control), 560 ml of CMW, 280 ml of CMW with 340 mg of encapsulated APM, 280 ml of CMW sweetened with 340 mg APM, 560 ml of an APM-sweetened soft drink (340 mg APM). Subjective hunger and food appeal were measured from 0930 a.m. to 1230 h, and food intake from a buffet lunch offered at 1205 h was measured. Treatment had no effect on food intake or macronutrient selection. Both 560 ml of CMW or soft drink suppressed appetite, although 280 ml of APM-sweetened mineral water significantly increased subjective appetite relative to the control. Encapsulated APM had no effect on appetite. Therefore, appetite reduction following consumption of an APM sweetened drink is likely due to drink volume and not the APM content. In addition, consuming APM-sweetened CMW produces a short-term increase in subjective appetite. PMID- 8451311 TI - Enhanced disruptive spatial learning effect after sufentanil in renal hypertensive rats versus normotensive rats. AB - The effects of the peripherally administered sufentanil citrate (S), a potent opioid agonist with high affinity for mu receptors on the spatial navigation task, were tested in normotensive Wistar (NR) and renal hypertensive rats (RHR). Rats were injected subcutaneously once daily in doses of 0.25 or 1 microgram/kg S before the water maze training. In NR rats, weak effects of 0.25 micrograms/kg S and impairments after 1 microgram/kg S were seen, whereas in RHR 0.25 and 1 microgram/kg S showed clearcut impairments. These data from the Morris water maze task support previous reports that RHR have an increased sensitivity for opioid agonists. PMID- 8451312 TI - Evidence for a direct central anorectic effect of tumor-necrosis-factor-alpha in the rat. AB - This study was designed to investigate the effect of tumor necrosis factor-alpha (TNF) on the control of food intake in rat. The specific aims were: a) to evaluate the effects of central (ICV) or peripheral (IP) microdoses of TNF on food intake; b) to show that the TNF-induced anorexia results from a direct action of the mediator on the central nervous system; c) to demonstrate that the anorexic activity of TNF is not due to nonspecific malaise. In the first experiment, ICV administration (0.5-4.0 micrograms) of recombinant-murine tumor necrosis factor-alpha (rmTNF) significantly reduced food intake in a dose dependent manner. The maximal effect (-66%) was observed 5 h after a 4.0 micrograms dose. In contrast, rm TNF did not affect feeding behavior when injected IP, indicating that the anorexic activity was centrally mediated. The estimated DE50 was 2.0 micrograms/rat by the ICV route. In the second experiment, the place conditioning paradigm was used to show that TNF administered ICV at 2.0 micrograms/rat did not induce aversive or deleterious effects as compared to naltrexone given IP at the equi-anorectic dose 5.0 mg/kg. It was concluded that TNF reduces food intake in rats by a direct action on the central nervous system. PMID- 8451313 TI - Learned preference and aversion for complete and isoleucine-devoid diets in rats. AB - Choice tests using flavored solutions were conducted to demonstrate a learned preference or aversion in rats fed replete (complete) or isoleucine (ILE)-devoid diets. In the first learning trial, rats demonstrated a preference for the flavored solutions paired with the replete diet at 6 and 24 h (p < 0.001), and an aversion for the solutions paired with the ILE-devoid diet at 6 h (p < 0.05). In the second trial, using a different concentration of tastant, rats ingested significantly more of the flavored solution paired with the replete diet at 24 h (11.4 +/- 3.0 g vs. 5.4 +/- 1.0 g, respectively; p < 0.05), and significantly more of a novel flavored solution than of the solution paired with the ILE-devoid diet at 24 h (12.4 +/- 2.4 g vs. 1.7 +/- 0.6 g, respectively; p < 0.001). These results suggest that learning contributes to the rat's ability to self-select diets that promote growth, and that a learning paradigm pairing flavored solutions with complete and indispensible amino acid-devoid diets may be used to demonstrate learned preferences and aversions for such diets in rats. PMID- 8451314 TI - Brain levels of amines and amino acids in taste aversion-prone and -resistant rats. AB - Possible biological contributions to taste aversion (TA) conditionability were explored by comparing whole-brain levels of five neurotransmitter amines and 14 common amino acids within TA-prone (TAP) and TA-resistant (TAR) rats. The selectively bred strains had been developed via 22 generations of bidirectional nonsibling matings based on susceptibility to cyclophosphamide-induced conditioned TAs. The target substances were separated by HPLC and were measured by electrochemical or fluorometric procedures. The TAP brains had higher levels of serotonin (5-HT) and lower levels of norepinephrine (NE) than TAR brains. No strain differences were found with respect to dihydroxyphenylalanine (DOPAC), dopamine (DA), or 5-hydroxyindoleacetic acid (5-HIAA). Among amino acids, TAP rats had lower levels of lysine than TARs: no other differences were detected. Therefore, higher levels of 5-HT and lower levels of NE and lysine were associated with enhanced TA conditionability. The 5-HT and NE results extend prior indications of their central neurotransmitter TA involvements. The functional role of lysine in TA or other brain functions remains obscure. PMID- 8451315 TI - Why cats pace on the treadmill. AB - There have been many studies suggesting that locomotion on a treadmill tends to be different than locomotion at similar velocities overground, but no satisfactory mechanical or neural mechanisms to account for the differences have been identified. The most prominent difference is the tendency to adopt a pacing gait for both walking and trotting speeds, in which the legs on one side of the body move in phase as lateral couplets rather than the typical diagonal couplet pattern seen overground. Using conventional video analysis, we quantified the gait patterns of intact, adult cats walking at various speeds overground and in a motorized treadmill. We noted that cats paced most frequently when they were at the front end of the treadmill enclosure, and that this gait was associated with an extended stride length that permitted the animals to maintain a higher duty factor of support (mean number of feet on the ground). We propose that the animal extends its stride specifically to improve the duty factor in anticipation of sudden stops of the treadmill belt and that it converts abruptly from diagonal to lateral gait because the extended stride results in collisions between ipsilateral hind and front feet. PMID- 8451316 TI - Effects of scheduled food and water access on circadian rhythms of hamsters in constant light, dark, and light:dark. AB - Wheel-running activity of 31 Syrian hamsters was monitored in constant light (LL), dark (DD), and light-dark (LD) under ad lib and restricted food and water access schedules. Free-running or damped circadian wheel-running rhythms of 26 hamsters in LL were entrained by exposure to the restriction schedule. The phase of entrainment was positive, i.e., wheel running anticipated access time. In LD, activity was nocturnal. When food and water were restricted to midlight, five hamsters showed additional activity in anticipation of access time. Thirty hamsters showed a small advance of the phase of nocturnal activity onset. In subsequent DD, anticipatory activity was revealed (unmasked) in several additional cases, and nocturnal activity shifted and entrained to the access schedule in 19 cases. The properties of food anticipation and entrainment under the three lighting conditions support a model of the hamster circadian system that incorporates separate but strongly coupled food/water- and light-entrainable pacemakers. PMID- 8451317 TI - Role of corticotropin-releasing factor (CRF) as a food intake regulator in goldfish. AB - The effect of intraperitoneal or intracerebroventricular corticotropin-releasing factor (CRF) administration on food intake has been studied in goldfish after 24 h of food deprivation. Food intake was evaluated at different time periods after injection, 0-2, 2-8, and 0-8 h. The 1 and 2 micrograms doses of CRF intracerebroventricularly administered induced a reduction in food intake during the first 2 h, although an increased feeding was observed in the next 6 h. The higher dose of CRF used in this study (3.3 micrograms) increased cumulative food intake at 8 h postinjection. However, intraperitoneal injection of 1 microgram CRF did not modify food intake in any of the studied intervals. These results suggest that CRF may play a role in central regulation of feeding behavior intake in goldfish, and show that CRF effects are time- and dose-dependent. PMID- 8451318 TI - Spatial but not object recognition is impaired by aging in rats. AB - Four groups of male Wistar rats (4, 8, 18, and 24 months) were submitted to object recognition and spatial recognition tests. Object recognition was not significantly affected by aging even at a longer retention interval. On the contrary, spatial recognition was significantly impaired in 18- and 24-month groups. The existence of two dissociable neural systems, respectively involved in object and spatial recognition, is discussed. PMID- 8451319 TI - Effect of fatty acid-rich diets on thymocyte proliferation and thymus involution during growing. AB - The effect of poly-unsaturated and saturated fatty acid-rich diet on the proliferation response of T and B lymphocytes in vitro was investigated. Also, a mitotic index of thymocytes and of thymus epithelial reticular-like cells and thymic involution coefficient were examined in vivo. w-6 PUFA-rich diet enhanced the rate of T (eightfold) and B (fourfold) lymphocyte proliferation, whereas saturated fatty acids did not show an important effect. However, both fat-rich diets increased the mitotic index of thymocytes and thymus involution index in vivo. These findings suggest that fat-rich diets may accelerate thymus involution during growing, possibly aggravating the impairment of the immune function which usually occurs under this condition. PMID- 8451320 TI - Changes in aggressive behavior, thermoregulation, and endocrine responses in BALB/cLac and C57Bl/6J mice under cold exposure. AB - Effect of cold exposure on aggressive behavior, on the concentrations of testosterone and glucocorticoids, as well as on the oxygen consumption at different ambient temperatures, and calorigenic effect of noradrenaline have been studied in BALB/cLac and C57Bl/6J males. Under normal temperature conditions, there have been no significant interstrain differences. After cold exposure (5 weeks at 6-8 degrees C), C57Bl/6J mice exhibited more pronounced adaptive changes in thermoregulation and endocrine status (increase of glucocorticoids and decrease of testosterone concentrations were less expressed in C57Bl/6J than in BALB/cLac). At the same time, males of this strain demonstrated more intensive aggression than BALB/cLac mice. Some relations between physiological and behavioral changes caused by cold exposure are discussed. PMID- 8451321 TI - The ability to arrange with conspecifics depends on social experiences around puberty. AB - The study examined the effect of age on the ability to arrange with unfamiliar conspecifics in differentially reared male guinea pigs. The experiments were conducted with 50-, 90-, 150-, and 210-240-day-old-males, which either had been reared in large colonies (CRM) or each with a single female (FRM). In each age class, seven pairs of unfamiliar CRM and seven pairs of unfamiliar FRM were placed in chronic confrontations for 6-10 days in the presence of an unfamiliar female in 2 m2 enclosures. Body weights were determined directly before and 52 h, 124 h, and 220 h after the onset of the experiments. CRM showed no substantial losses in body weights irrespective of whether the experiments were conducted before, around, or after sexual maturity (which is achieved at 2-3 months of age). In contrast pairs of FRM arranged without problems only at 50 days of age. Around puberty, social stress distinctly increased, and 2 and 4-5 months later the confrontations even had to be ceased after 6 days, because losers extremely decreased in body weights. It is concluded that in male guinea pigs the time around sexual maturity is crucial for the development of social skills necessary to arrange with unfamiliar conspecifics in a nonstressful way. PMID- 8451322 TI - A modularized infrared light matrix system with high resolution for measuring animal behaviors. AB - The current study provides a new modularized infrared light matrix system (about $200 cost) which is designed to measure the horizontal gross or fine movements, vertical motion, clockwise or anticlockwise turnings, freezing time, and total distance traveled in rats. The system records the sequences of animal's activity in a computer-aided system with a resolution of 0.2 s in time or 1.6 cm in space, and permanently stores all the resulting data in file. The behavioral apparatus was tested for its sensitivity and usability by amphetamine-injected rats. It was found that intraperitoneal administration of amphetamine (1.25-2.50 mg/kg), but not normal saline, produced a dose-related increase in either the horizontal gross or fine movements, vertical motion, clockwise or anticlockwise turnings, or total distance traveled. However, amphetamine injections produced a dose-related decrease in freezing time. Apparently, most of the amphetamine-induced responses obtained by other detecting apparatus can be reproduced easily by the present apparatus. The current detection system possesses the following advantages: a) high resolution, b) high expansion potential, and c) precise and simplified algorithms for behavioral parameter analysis. PMID- 8451323 TI - Taste and smell sensations enhance the satiating effect of both a high carbohydrate and a high-fat meal in humans. AB - The effects of meal sensory properties (tasty vs. bland) and nutrient composition [high-CHO (carbohydrate) vs. high-FAT] on hunger ratings, blood glucose and free fatty acids (FFA), taste perception, and subsequent food intake, were studied in human subjects. Aspartame and vanilla were used to augment meal palatability, yielding four isocaloric liquid meals: bland-FAT, tasty-FAT, bland-CHO, tasty CHO. Normal-weight, nondieting young adults consumed each of the meals for breakfast on separate days. The main finding was that tasty versions of high-FAT and high-CHO meals were more satiating than nutritionally identical bland meals, as indicated by a greater decrease in hunger ratings following the tasty meals. Changes in blood glucose and FFA were related to meal nutrient composition, but not to meal sensory properties. High-CHO meals tended to be more satiating than high-FAT meals. Consumption of each of the meals produced a similar decrease in pleasantness ratings of food-related tastes. Intake of carbohydrates was significantly higher at a self-selected lunch 5.25 h following a tasty breakfast. These findings indicate that hunger is decreased to a greater extent by meals flavored with aspartame and vanilla relative to nutritionally identical, unflavored meals. The satiety-enhancing effect of oral stimulation was found for both high-FAT and high-CHO meals. PMID- 8451324 TI - Afferent control of pressor responses to feeding in young rats. AB - A series of experiments investigated the eliciting stimuli and physiological systems involved in triggering the blood pressure (BP) response to feeding in the young rat. The studies included 1) tongue cannula (TC) infusions of milk to nipple-attached and unattached pups; 2) TC infusions of saline, sucrose, and water to nipple-attached pups; 3) maternal milk ejections to 3-week-old pups that rarely have stretch responses; 4) gastric cannula infusions of milk to nipple attached pups; and 5) maternal milk ejections and TC infusions to pups whose mouths were topically anesthetized. The results implicate the contact of fluid with oral and/or lingual surfaces as the critical stimulus primarily responsible for the BP rise. Although nipple attachment appears to be an important precondition for the typical pressor response, the co-occurrence of a behavioral stretch response is not essential. PMID- 8451325 TI - Some psychosomatic causal factors of restraint-in-water stress ulcers. AB - Rats were stressed by 75 min restraint in a tube suspended vertically while dry (19 degrees C) or partially immersed in tanks of water at different temperatures (19, 27, 35 degrees C), either in a conscious state or while under pentobarbital anesthesia. Restraint was followed by 75 min rest in the home cage and then sacrificed under halothane anesthesia. Assessment of the degree of gastric erosion indicated that restraint alone, whether the animal was rendered unconscious or not, was not sufficient to induce ulceration. However, in conscious animals, the addition of partial immersion did induce ulceration that was inversely related to the temperature of the water bath. This effect was not merely the result of brain stem and spinal reflex processes, because unconscious animals exposed to the most severe conditions (19 degrees C) showed no ulceration. PMID- 8451326 TI - Salivary testosterone in children with and without learning disabilities. AB - Previous studies have indicated that the sex steroids have organizational effects upon neural tissue and that abnormal secretion during development may lead to functional anomalies. In this study, we explore the possibility of prepubertal steroid hormone involvement in the etiology of learning disabilities. Salivary testosterone levels in 264 children without learning disabilities (133 males, 131 females) were measured and compared to that in 32 children with learning disabilities (25 males, 7 females). The presence of learning disabilities was significantly associated with higher salivary testosterone. Data from equivalent samples of learning-disabled and control subjects also were compared separately because of disparities in sample size and variable distribution in the total group analysis. A 32-member sample of nonlearning-disabled children was created by randomly selecting individuals who exactly matched the age, race, and sex characteristics of the learning-disabled group. The matched analysis further substantiated the association between testosterone secretion and learning disabilities. Thus, it is possible that some learning disabilities may be associated in part with abnormal testosterone levels. PMID- 8451327 TI - Peripheral olfactory deafferentation of the primary olfactory system in rats using ZnSO4 nasal spray with special reference to maternal behavior. AB - A modified method of applying ZnSO4 to the olfactory mucosa is described. Treated rats experienced severe nasal congestion that cleared within 24 h; more persistent morbidity did not occur. Nonpregnant females observed with male intruders 24 h following ZnSO4 showed no alterations in behavior other than a reduction in anogenital sniffing, indicating that they were not hypoactive or irritable. In other experiments, lactating females were observed in a hole-board apparatus; 2 days posttreatment anosmia was confirmed in 80% of bilaterally ZnSO4 treated females by the absence of preference for pup odors. After bilateral but not unilateral ZnSO4 treatment, initially activity scores and nose pokes were equivalent in all groups, but later they both were lower than in controls, probably due to a more rapid habituation to the novel apparatus. We conclude that intranasal ZnSO4 by small-volume spray is a useful experimental tool. PMID- 8451328 TI - The effect of subjective and physiological arousal on dishabituation of salivation. AB - We have previously shown that salivation to the same food habituates, and recovers after presenting novel nontaste stimuli. This study assessed the effects of environmental stimuli that differentially influence subjective and autonomic arousal on dishabituation of salivation. Thirty female subjects were preloaded on a lemon yogurt milkshake and habituated to seven presentations of lemon juice. Prior to the eighth presentation of juice, subjects were presented an engaging video game designed to produce subjective but no autonomic arousal (LO), a video game plus mental arithmetic stressor, designed to produce both subjective and physiological arousal (HI), or a no stimuli (REST) control. Significant dishabituating effects of HI versus REST were shown for salivation. Heart rate was significantly higher during the dishabituator for HI than LO or REST conditions, which were equal. Finally, significant differences in arousal were shown between each of the three conditions. These results show salivation can be differentially dishabituated by nonfood stimuli, and these stimuli influence salivation without influencing subjective hunger or hedonics. PMID- 8451329 TI - Response to removal from and return to a social group in adult male rhesus monkeys. AB - The removal of four adult rhesus monkeys from a large social group (n = 85) to peer housing resulted in no significant changes in basal cortisol levels or absolute numbers of T lymphocyte subsets 24 h later. However, the return of these males 1 year later to the same social group resulted in significant increases in cortisol levels (66 +/- 21%) and significant decreases in T-helper (-31.6 +/- 15.8%) and T-suppressor cells (-35.2 +/- 8.7%) 24 h later. Blood samples for immune and cortisol measurements were obtained before and 24 h following both the removal and the return 1 year later. Aggressive and sexual behavioral data were recorded on audiotape for 3.5 h following the reintroduction using an all occurrences of some behaviors sampling technique. Analyses revealed a negative correlation between percent change from baseline in T-helper cells 24 h following the return and the frequency of bites (nonwounding) and chases received during the 3.5 h following the return. The absence of a stress response to separation in adult males is in contrast to the presence of a stress response observed in infants, juveniles, and adult females and possibly is due to sex differences in group attachment in sexually mature males. On the other hand, the return to the social group did induce a psychosocial stress response in the males, and the degrees of the stress, as determined by cortisol and immune cell measures, was related to the agonistic interactions experienced by the individuals. PMID- 8451330 TI - Water deprivation produces an exercise-induced weight loss phenomenon in the rat. AB - Rats given restricted feeding and allowed free access to activity wheels increase activity, decrease food intake, and lose body weight compared to nonexercised controls. The phenomenon is of interest because of the relationship between exercise and anorexia nervosa. This study determined if another factor that energizes behavior in rats, water deprivation, produces similar exercise-induced weight loss. Rats were maintained on a restricted water schedule (10 min/day) combined with free access to running wheels and food; controls had no wheel access or were food deprived only. Both water-deprived groups consumed similar amounts of food and water, with the exercised group losing more body weight. Plasma osmolality, hematocrit, and posterior pituitary vasopressin content were equivalent in the two water-deprived groups, indicating similar hydrational status. It is concluded that the weight loss effect in water-deprived rats is due to excessive voluntary exercise, and that other factors that energize behavior should produce a similar effect. PMID- 8451331 TI - Pathways linking the olfactory bulbs with the medial preoptic anterior hypothalamus are important for intermale aggression in mice. AB - Manipulations affecting olfaction, as well as bilateral lesions of the medial preoptic anterior hypothalamic (MPAH) continuum, decrease intermale aggression in mice. In the present study, unilateral removal of an olfactory bulb was combined with a contralateral lesion of the MPAH. This surgery, like bulbectomy and bilateral lesions of the MPAH, substantially decreased aggressive behavior. This surgery bilaterally destroys the ipsilateral links between the olfactory bulbs and the MPAH, and it is this disruption that presumably causes the decrease in aggression. The effect is not due to removal of an olfactory bulb combined with hypothalamic damage per se, because ipsilaterally lesioned/bulbectomized males continued to fight without decrement after surgery. These results provide compelling evidence that multisynaptic neural pathways linking the chemosensory systems of the olfactory bulbs with the rostral hypothalamus are involved in the regulation of intermale aggression in mice. PMID- 8451332 TI - Season affects tolerance of cohabitation by deer mice. AB - We measured the resting metabolic rates of Peromyscus maniculatus for 7 days before and 7 days following forced pairing in order to determine whether seasonal light cycles influenced the rates of behavioral and metabolic habituation of deer mice to cohabitation. We had earlier shown that winter photoperiod and/or huddling results in lower resting metabolic rates and core temperatures of deer mice. Seasonal photoperiods were simulated by conditioning wild-caught mice to 24 h light cycles with differing durations of light exposure during the 24 h day. These experiments demonstrated that winter mice adjusted their resting metabolic rates from solitary to huddling levels much more rapidly than summer mice. Initial, high metabolic rate responses of paired mice persisted much longer than expressions of agonistic behaviors between paired mice. We propose that winter photoperiod enables animals to more efficiently make the transition to spontaneous, amicable huddling as a winter acclimatization strategy. PMID- 8451333 TI - An adaptable microcomputer program for monitoring behavior. AB - We describe an improvement of a flexible and easy to use program for monitoring and recording behavior durations with IBM-compatible microcomputers and a companion program that provides additional versatility for handling data. Up to 35 behaviors or events can be monitored, and processing speed is fast enough to measure even very rapidly performed behaviors. No specialized hardware is required, and the data files that are created are compatible with commercially available software packages for statistical analysis. PMID- 8451334 TI - Automatic and effortful processing in depression. AB - Automatic processes require few attentional resources, but effortful processes use attentional capacity. Research on cognitive processing by depressed individuals is reviewed and the following is concluded: (a) Depression interferes with effortful processing. The degree of interference is determined by the degree of effortfulness of the task, the severity of depression, and the valence of the stimulus material to be processed. (b) Depression interferes only minimally with automatic processes. Hypothetical causal mechanisms for interference in effortful processes by depression, whether interference in effortful processing is unique to depression or characteristic of psychopathology in general, and whether negative automatic thoughts are associated with current depression or depression proneness are also addressed. The effortful-automatic perspective has implications for understanding depressive clinical features, treating depression, and conducting future research. PMID- 8451335 TI - Behavioral correlates of individual differences in road-traffic crash risk: an examination method and findings. AB - This article considers methodological issues relevant to the study of differential crash involvement and reviews the findings of research in this area. Aspects of both driving skill and driving style appear to contribute to crash risk. Of the former, hazard-perception latency appears to play an important role, and this may be attributable to generalized abilities to identify visual targets in a complex background and to switch attention rapidly. Of the latter, faster driving speed and willingness to commit driving violations increase crash risk, and these factors may be explicable in terms of personality and antisocial motivation. The article concludes with an examination of the practical implications and of the ways in which research in this area might usefully proceed. PMID- 8451336 TI - Contextual sources of information and responses to animal communication signals. AB - The response of signal recipients depends on information found in the signal itself and on other information sources known collectively as context. Context is the set of events, conditions, and changeable recipient characteristics that modify the effect of a signal on recipients' behavior. Sources of contextual information include (a) the characteristics of the recipient and (b) sources external to the recipient (the signaler and the setting). Contextual information is most commonly used when the signal itself does not provide enough information for the recipient to behave adaptively. The signal's referent may be ambiguous or deceptive, or recipients may need additional information to fine-tune their responses. When animal signals were thought to be information poor, contextual information was seen as being critically informative. Animal signals are now known to be much more informative, but even information-rich systems, such as human language, depend heavily on contextual sources of information. PMID- 8451337 TI - On resolving the enigma of infantile amnesia. AB - Historical and current theories of infantile amnesia are examined. To evaluate the viability of these theories, as well as the phenomenon of infantile amnesia itself, a review of memory development from birth through the preschool years is provided, including an overview of relevant perceptual and neurological maturation. In the context of this review, extant theories of infantile amnesia are shown to falter, and it is concluded that infantile amnesia is a chimera of a previously unexplored relationship between the development of a cognitive sense of self and the personalization of event memory. This hypothesis is examined in detail and discussed in the context of related developments in language and social cognition. PMID- 8451338 TI - Analogue versus clinical depression: a critical reappraisal. AB - Much of the existing psychological literature on depression is based on research with college students. An important question is whether depression in college students represents an appropriate analogue of depression in clinical patients. The purpose of the present article is to review past evidence on this issue from a critical perspective. Past arguments are examined, and little support is found for the position that depression research with college students is not warranted. Moreover, the results of studies with student and clinical samples are compared, and the findings are generally similar across populations. Next, a number of methodological issues are identified that may actually favor the use of depressed college students, and some methodological recommendations for future research are outlined. Finally, an appeal is made for research that directly examines the analogue-clinical issue and the nature of college student depression. PMID- 8451339 TI - Absolute pitch. AB - Absolute pitch (AP) is the ability to identify a tone's pitch or to produce a tone at a particular pitch without the use of an external reference pitch. AP exists in varying degrees among people generally described as AP possessors. AP possessors vary not only in the accuracy with which they can identify pitches but also in their ability to produce pitches absolutely and in their ability to identify tones of various timbers and in various pitch registers. AP possessors' memory for pitches is mediated by verbal pitch names; they do not have superior memory for pitches per se. Although the etiology of AP is not yet completely understood, evidence points toward the early-learning theory. This theory states that AP can be learned by anyone during a limited period early in development, up to about age 6, after which a general developmental shift from perceiving individual features to perceiving relations among features makes AP difficult or impossible to acquire. PMID- 8451340 TI - Psychological effects of severe burn injuries. AB - Severe burn injuries provide researchers with an opportunity to study the effects of painful but usually transient trauma on psychological functioning. To that end, this article presents a review of the 3 main areas of this body of literature: (a) premorbid characteristics of people who sustain severe burn injuries, (b) psychological reactions during hospitalization, and (c) long-term adjustment. The general implications of these studies are discussed and then used to illuminate the circumstances under which individuals suffer the most from this type of trauma, the effects of such injuries on personality function, and how meaningful units of measurements can be defined. Potential clinical applications are also described. PMID- 8451342 TI - Behavior problems in preschool children: a pilot study. AB - Behavior problems in 20 preschool children (13 boys, 7 girls) referred to a diagnostic nursery were assessed using parents' ratings. The patterns of behavior problems reported in 4- and 5-yr.-olds parallel those noted for older clinic referred children (i.e., internalizing difficulties in girls, externalizing difficulties in boys). The most salient behavior problems for 3-yr.-olds involved aggression. Correlations between children's behavior problems and an index of parents' experienced stress were moderate (.44 to .64). PMID- 8451341 TI - Antibody response and some behaviors as differential traits between two inbred strains of mice (C57BL/6 and BALB/c). AB - The goals of this research were to find out if the antibody response and some behaviors are differential traits for murine strains C57BL/6 and BALB/c and to study the influence of strain and isolation on both behavior and the antibody response. 21 C57BL/6 male mice and 28 BALB/c male mice were used; of those, 11 C57BL/6 and 16 BALB/c were kept isolated, and the remaining mice were housed 2 per cage. The tests were Open-fields 1, 2, and 3 (of varying light and sound stimulation), holeboard, light-darkness test, immunization with rat erythrocytes; in addition, the mice were weighed. The traits that best differentiated both strains (according to discriminant analysis) were weight, IgM primary response, and emotional behavior (ambulation, rearing, and defecation in stimulating open fields). Social isolation (of adult mice) influenced emotional behavior, but not the antibody response. PMID- 8451343 TI - Measuring persistence and personality characteristics of adolescents. AB - The concept of persistence (to hold firmly and steadfastly to some purpose or task) has been reportedly related to personality development, motivation, and locus of control. However, there is a dearth of research on persistence primarily because a widely accepted and validated measure of persistence is lacking. A 1987 measure, the Persistence Scale for Children by Lufi and Cohen, has been the subject of validation and reliability studies. The present paper is a description of its use with 50 adolescents and the correlations between persistence and the adolescents' personality characteristics, based on Cattell's High School Personality Questionnaire. Correlations between persistence and HSPQ personality characteristics were significant. Replication with a larger sample and continued use in the study of persistence is discussed as well as persistence in relation to adolescent development. PMID- 8451344 TI - Comparison of the effects of auditory subliminal stimulation and rational-emotive therapy, separately and combined, on self-concept. AB - The present study investigated the effects on self-concept of Rational-Emotive Therapy and auditory subliminal stimulation (separately and in combination) on 141 undergraduate students with self-concept problems. They were randomly assigned to one of four groups receiving either Rational-Emotive Therapy, subliminal stimulation, both, or a placebo treatment. Rational-Emotive Therapy significantly improved scores on all the dependent measures (cognition, self concept, self-esteem, anxiety), except for behavior. Results for the subliminal stimulation group were similar to those of the placebo treatment except for a significant self-concept improvement and a decline in self-concept related irrational cognitions. The combined treatment yielded results similar to those of Rational-Emotive Therapy, with tentative indications of continued improvement in irrational cognitions and self-concept from posttest to follow-up. PMID- 8451345 TI - Ratings of an interview outline for evaluation of disruptive adolescents. PMID- 8451346 TI - Development and validation of a self-critical cognition scale. AB - A 13-item Self-critical Cognition scale was developed to measure a self-critical and self-defeating cognitive tendency in processing self-relevant information. The scale, administered to 561 male and female university students, evidenced high internal consistency (alpha = .89) and test-retest reliability of r138 = .83 over a 6.5-week interval. A factor analysis yielded a most interpretable 2-factor solution, Factor 1: negative self-processing and Factor 2: failure in positive self-processing. The scale's construct validity was supported by meaningful correlations of -.71 with Rosenberg's self-esteem, .43 with Watson and Friend's social anxiety and distress, .62 with Cheek and Buss's shyness, .57 with Watson and Friend's fear of negative evaluation, .42 with Beck and Beamesderfer's depression, and .34 with negative adjective counts in spontaneous adjective listing in a self-descriptive task. Use of the scale for experimental and clinical research is suggested. PMID- 8451347 TI - Adapting projective tests for minority children. AB - Child abuse reporting laws have placed new demands upon law enforcement, human service agencies, and clinicians alike. For the clinician, these demands are compounded when minority children are involved. Few of the standardized measures seem to fit all cultural groups. In our situation the cultural mix involves Hispanic, Mexican, and American Indian children. We found a combination of two projectives, the Draw-A-Person/Draw-A-Family and the Thematic Apperception Test, to fit our multicultural needs. Specifically, we use the D-A-P drawings of the child and his/her family as "plates" and then apply the TAT "tell me a story about this picture" technique. PMID- 8451348 TI - Control beliefs of adults in three domains: a new assessment of perceived control. AB - Preliminary analyses (N = 205; age range 30 to 80 years) were performed with a new measure of perceived control to assess control beliefs in specific domains, examine cross-sectionally groups' age differences in perceived control and compare control beliefs for the various domains within age groups. This measure was hypothesized to yield greater conceptual clarity of the assessment of perceived control than other instruments by measuring specifically beliefs about control over desired outcomes without confounding these with beliefs about what it takes to get desired outcomes. Factor analyses clearly supported separation of control in the cognitive, social, and health domains. Intercorrelations indicated generally low relations among the three factors, and internal consistencies indicated satisfactory reliability. Participants in their 70s showed in the cognitive domain significantly lower perceptions of control than individuals in their 30s, 40s, and 50s, in the health domain significantly lower perceptions of control than individuals in their 60s, and in the social domain significantly lower perceptions of control than individuals in their 40s and 50s. Generally, for all three domains a stability in in control beliefs appeared across the age groups studied until the 70s, at which age there was a significant drop in mean control beliefs. Mean differences in control beliefs among domains within age groups were nonsignificant. PMID- 8451349 TI - Speaking anxiety, achievement, and crime: a response to Boor and Bair. AB - Use of context and conditional language provide perspective for preliminary data intended to stimulate research. PMID- 8451350 TI - Effects of background music on anxiety, satisfaction with communication, and productivity. AB - Previous research on music's influences has often been nonconclusive, partly because subjective measures have been used for testing opposite conditions such as sedative versus stimulative music or happy versus sad music. Here, background music's influence upon 104 conversants was explored by manipulating the presence of music, and when present, by the more objectively assessed structural elements of mode and speed. Conversations taking place in the presence of background music were rated as more satisfying. Major mode music elicited higher ratings of satisfaction with communication than minor mode. Modality and speed interacted, illustrating the importance of not confounding music's structural elements when testing opposite conditions in studies of the effects of music. While background music did not affect productivity relative to no music, those hearing background music achieved greater productivity when music was in the major mode. PMID- 8451351 TI - Relationship of students' affective learning to teachers' type A scores. AB - In a study of 107 college teachers, perceptions of college students' affective learning were positively associated .62 with teachers' self-reported Type A behavior scores. PMID- 8451352 TI - Projective techniques: an international perspective. AB - This is a review of findings from four recent surveys on use of clinical tests in the United States, The Netherlands, Japan, and Hong Kong. The preliminary analysis indicates that projective techniques are popular in the assessment of personality worldwide. Obviously, projective tests are 'universal' in that unstructured stimuli serve as the basis for assessment and do not pose a language barrier. Also, reliance on projective methods may reflect problems in access to adequately translated and standardized objective tests. More data are needed from developed countries before firm conclusions on the international status of projective techniques can be affirmed. PMID- 8451353 TI - Development and construct validity of a self-description inventory for African adolescents. AB - The present study presents evidence for the reliability and validity of a new measure of self-concept for African adolescents. Procedures for giving the 50 item scale are described. The Self-description Inventory was administered to 634 students in Standards 8 and 9 of two coeducational high schools. Factor analysis clearly identified the eight subscales. The multidimensionality of self-concept among African adolescents is indicated and supports the construct validity. Implications for continued study are mentioned. PMID- 8451354 TI - Psychophysiological effects of several stress management techniques. AB - The purpose of this study was to assess the psychophysiological stress-reducing properties of progressive relaxation compared with hypnosis, and deep abdominal breathing compared with a baseline condition, while controlling for hypnotizability. 231 nursing students experienced the baseline procedure and progressive relaxation in Session 1 and deep abdominal breathing and hypnosis in Session 2 about a week later. Before and after each technique peripheral skin temperature and pulse rate were assessed. Separate analyses of variance, computed for the first and second sets of techniques, indicated that progressive relaxation and hypnosis both increased skin temperature and reduced pulse rate, suggesting reduced psychophysiological responsivity. Deep abdominal breathing was associated with a significant reduction in physiological responsivity (skin temperature) relative to baseline. Hypnotic susceptibility had no effect on the psychophysiological measures. PMID- 8451355 TI - Contributing factors associated with agoraphobia. AB - 24 agoraphobics, 6 panic subjects, and 27 normal controls were compared on several factors assumed to be associated with agoraphobia. As compared to controls, agoraphobics scored higher on these factors, but, in general, there were no differences between agoraphobics and panic subjects without agoraphobia. PMID- 8451356 TI - Seasonal changes in rule infractions among prisoners: a preliminary test of the temperature-aggression hypothesis. AB - To test the temperature-aggression hypothesis, seasonal changes in aggression as indexed by reported rule infractions were studied for prisoners located at the Patuxent Institution, Jessup, Maryland. 5383 reports of rule infractions occurred between July 1987 and March 1991. Rule infractions occurred more frequently during the hot summer months than the three other seasons of the year. This summer effect, though significant, is only a few percent above a theoretical chance level based on the number of days comprising the seasons. A much stronger monthly effect over 45 months was found, but the bases of erratic fluctuations are not known. PMID- 8451357 TI - Social support and suicide. AB - Although considerable research from varied theoretical perspectives and across multiple disciplines has linked social support and suicide, few researchers have explored the relationship directly with any specificity. Investigators are encouraged to consider not only the type or source of support and related network characteristics, but also the specific role of support, the type of suicidal behavior examined, the type or source of stress across both temporal (i.e., acute vs chronic) and qualitative dimensions (i.e., desirable vs undesirable), particular features of the samples accessed, as well as potential interactions with a host of theoretically related variables such as problem-solving skills or adaptive coping. PMID- 8451358 TI - Gender and age differences in college students' alcohol consumption. AB - Respondents (86 men and 141 women) enrolled in classes at a large university in the Midwest participated in this study, designed to examine the role gender and age play in the consumption of alcoholic beverages. The hypotheses that age and gender would produce significant effects were supported. Men reported significantly greater alcohol consumption than did women. In addition, there was a significant interaction between gender and age. Women under legal drinking age had higher rates of consumption than women of legal drinking age or older, while the opposite pattern was found for men. The long-term pattern of alcohol consumption may be different for men than for women. During the college years, women seem to moderate their consumption. Finally, these results indicate that illegal, underage drinking by men and women occurs at a high rate. Research should be designed to evaluate the extent of the problem. PMID- 8451359 TI - Erotic paranoid reaction, the imaginary lover, and the benign conspiracy. AB - This paper describes how an erotic paranoid reaction, when linked to fantasies of benign conspiratorial persecution by the hospital and the milieu, might merge as the grandiose messiah-complex. PMID- 8451360 TI - Case study of a schizophrenic patient during social skills training in a forensic psychiatry ward. AB - A schizophrenic patient's behaviour was monitored over 12 weeks using the Assessment Schedule and Adult Training Instrument, the patient's self-reports of his symptoms of anxiety, scores on the Social Behaviour Schedule, and the frequency of nocturnal enuresis. Contrary to expectations, the patient's functioning deteriorated generally, with the exception that the trend of deteriorating behaviour, as assessed by hospital staff, appeared to have slowed down during a period involving activities out of the ward. PMID- 8451361 TI - Serum cholesterol levels and severity of aggression. PMID- 8451362 TI - Use of the Rorschach with Hispanic Americans. AB - The rationale for and overview of research on the performance of Hispanic Americans on the Rorschach was addressed. Recommendations for further research were made. PMID- 8451363 TI - MMPI Scale 9 changes in incarcerated felons. AB - This article focuses on the scores of incarcerated male felons on the MMPI clinical subscales 4 and 9 because they are the most frequently elevated for this type of population. Over time, while scores on Scale 4 remained consistent, those on Scale 9 declined significantly. That inmates might become depressed, as a result of the foibles of incarceration, is discussed. PMID- 8451364 TI - Brain, environment, heredity, and personality. AB - Behavior genetics research, committed to a model of the origins of personality and intellectual development restricted to heredity and environment, consistently generates evidence for two types of environmental influences. One of these, termed the between-family or shared environment, creates no conceptual problems. The other, termed the nonshared or within-family or unique environment, does. The other, termed the nonshared or within-family or unique environment, does. The latter accounts for a substantial portion of the variance in personality and intellect, it must be unique to each individual, and its origin has not been determined. It is contended here that the brain itself, as an inherently indeterminate dynamic system, is the source of this unresolved developmental variability. PMID- 8451365 TI - Measuring change in a brief therapy of a compulsive personality. AB - In the short-term therapy over 16 50-min. sessions of a compulsive personality, there were unanimous positive changes on 17 verbal measures, with no activity shown on one measure. The verbal measures of Mahl, Raimy, and Bugental were used, along with Buhler, Buhler, and Lefever's Basic Rorschach Score and a qualitative analysis of the Rorschach. There were indications of decreases in procrastination, narcissism, and disorderliness. PMID- 8451366 TI - Relation of birth order and scores on measures of pathological narcissism. AB - To study the relationship between birth order and pathological narcissism, it was predicted that firstborn and only children would score significantly higher on standardized measures of pathological narcissism. Two such measures, the Millon Clinical Multiaxial Inventory and the Narcissistic Personality Inventory, were administered to 50 randomly selected subjects from a metropolitan mental health and family treatment agency. Subjects were asked to indicate their ordinal birth positions, e.g., first, middle, last, or only, and then were administered both instruments. Analysis supported the initial prediction by indicating that firstborn and only children had higher mean scores on the measures of pathological narcissism. It might be advisable for clinicians to identify patients' ordinal positions while appraising relevant diagnostic criteria and eventual treatment planning. PMID- 8451367 TI - Affiliative behavior in different species of voles (Microtus). AB - Data were collected on the huddling behavior of pine voles, Microtus pinetorum, and meadow voles, M. pennsylvanicus, to supplement earlier data on prairie voles and montane voles. Species that are social/monogamous in the field tended to huddle more in the laboratory. Contact proneness may be one factor driving different mating systems in the field. PMID- 8451368 TI - Theology and paranoia: the search for meaning. AB - This paper describes how a paranoid patient, having feelings of guilt and fear and a messianic grandiosity, may construct a teleology based on cosmic bisexuality, by which meaning may be given to his suffering. PMID- 8451369 TI - Cooke's disturbance index on the MMPI-2. AB - The shortened scales of the Minnesota Multiphasic Personality Inventory-2 can affect the magnitude of Cooke's 1967 disturbance index. Methods are given to adjust scores on those scales before calculating the index. PMID- 8451370 TI - Utility of computer interpretive reports based on counselors' ratings of the Diagnostic Inventory of Personality and Symptoms. AB - The accuracy and clinical utility of computerized interpretive reports for the Diagnostic Inventory of Personality and Symptoms were explored for 540 clients of a drug treatment center. The modal profile for substance abusers was identified and the accuracy of the substance abuse scales was assessed. 9 chemical dependency counselors rated the computer reports for usefulness and compared these retrospectively with similar reports based on the MMPI and Millon's MCMI. The results suggested the Diagnostic Inventory of Personality and Symptoms accurately identifies substance abusers, provides useful information for treatment, and offers a cost-effective alternative to the MMPI and MCMI. PMID- 8451371 TI - Self-reinforcement scores of psychiatric inpatients and normal controls. AB - Heiby's 1982 self-reinforcement questionnaire (a measure of the ability to reward oneself selectively for constructive behaviors or efforts and to nurture a positive self-image by means of a supportive internal speech) was administered to 12 normal controls (psychiatric nurses), 11 paranoid schizophrenic patients (DSM III--R), 8 bipolar patients currently manic (DSM-III--R), and 12 inpatients treated for substance abuse (DSM-III--R). No significant mean differences were found on analysis of variance. The means of the groups of psychiatric inpatients and of normal persons are comparable to means of other samples of normals, e.g., college students or factory workers, reported in the literature. PMID- 8451372 TI - Legal abortions and neonatal homicide after Roe v Wade. PMID- 8451373 TI - Primary school teachers' beliefs and advice to parents concerning sugar consumption and activity in children. AB - The available body of scientific evidence does not support the notion that sugar consumption has significant adverse effects on children's behaviours; however, responses to a mailed questionnaire indicated that more than 80% of 389 Canadian primary school teachers believed that sugar consumption contributes to increasing activity of normal children and to the behavioural problems of hyperactive children. Moreover, in the previous three years, 55% of all respondents had counselled the parents of children whom they believed to be hyperactive to consider reducing their child's sugar consumption to control the child's activity, and parents frequently did so. These results indicate that teachers need to be provided with accurate and up-to-date information about the effects of sugar on children's behaviour and about effective treatments for hyperactivity. Possible origins of beliefs about the reputed adverse behavioural effects of sugar and about factors that may serve to perpetuate these beliefs are discussed. PMID- 8451375 TI - Lost-letter technique: attitudes toward gay men and lesbians. AB - As only 10 of 210 "lost" postal cards with messages supportive of lesbian, gay male, and elderly artists were returned after 30 days, careful methodological study is needed. PMID- 8451374 TI - Depressive symptomatology among rural youth: a test of the circumplex model. AB - This study assessed the utility of the circumplex model in predicting depression among 108 rural youth. Only cohesion was linearly related to depression, but the r of -.23 may underestimate the association if the variables are not linearly related. PMID- 8451376 TI - Self-esteem: the effects of life-satisfaction, sex, and age. AB - A self-report questionnaire was administered to 1726 subjects to examine the effects of life-satisfaction, sex, and age on self-esteem. Subjects were grouped into 3 age groups, 17-22, 23-29, and 30-40 years. Analysis yielded significantly higher self-esteem for men than women, amongst older subjects, and for those with high life-satisfaction. These findings were interpreted in terms of various theories. PMID- 8451377 TI - A radon generator/delivery system. AB - A radon-generating system is described in which 222Rn, emanating from 226Ra stored in an aluminum containment vessel, may be pumped into a syringe for subsequent injection into a standard spinner flask containing tissue culture medium. The radium-containment vessel is sealed by an indium gasket and three metal bellows valves, one of which was used to fracture the glass capsule that contained 2.9 GBq of radium salt. A rotating piston pump transfers radon-enriched air from the radium-containment vessel to a delivery loop that includes a transfer syringe. The flow of air and radon through the loop is manipulated by three crossover ball valves, one of which may be set to fill the syringe. A charcoal trap is provided to collect residual radon left in the delivery loop after the transfer syringe has been filled. The protocol used to expose cells to radon and its progeny is described as well as the dosimetry that is used to estimate the dose delivered to the cells. A description of safety precautions taken in fabricating the generator and in conducting radiobiological studies is also presented. PMID- 8451378 TI - Concerning plasmon excitation in liquid water. AB - The existence of plasmon excitation produced by the interaction of fast charged particles in liquid water is examined critically from the theoretical point of view. By the analysis of the Fano index at different excitation energies and by comparing the real and imaginary parts of the dielectric function for both the liquid and the gas at unit density, we find no convincing evidence for plasmon excitation in the condensed phase of water. A density and a condensation effect on the dielectric function are observed. Implications of this finding for diffusion kinetics are discussed briefly. A procedure for the determination of the real and imaginary parts of the dielectric function from the dipole oscillator strength distribution is presented. PMID- 8451379 TI - Radiobiology of alpha particles. IV. Cell inactivation by alpha particles of energies 0.4-3.5 MeV. AB - In this report the effectiveness of low-energy alpha particles in the range 0.4 to 3.5 MeV for cell killing is investigated. Four cell lines of different nuclear dimensions (AG1522, C3H 10T1/2, CHO-10B, and HS-23) are studied. Monte Carlo simulations are carried out to interpret the experimental results. They are presented as a function of dose to the nucleus, the total track length of alpha particles in the nucleus, and other parameters. It is found that the effectiveness of alpha particles for cell killing decreases with decreasing alpha particle energy. The maximum RBE value is found to extend to LET values as high as 180 keV/microns. Although the LET might be the same, the effectiveness of alpha particles for cell killing is higher in the ascending part of the Bragg curve compared to descending part of the Bragg curve. The terminal tracks of alpha particles are observed to be less effective for cell killing. PMID- 8451380 TI - Dose- and source-size-related changes in the late response of pig skin to irradiation with single doses of beta radiation from sources of differing energy. AB - Late radiation damage to pig skin has been assessed at 104 weeks after exposure to sources of 90Sr/90Y (Emax 2.2 MeV) and 170Tm (Emax 0.9 MeV). Damage was assessed from measurements of dermal thickness in histological sections of irradiated skin and was compared with that of unirradiated skin to establish the relative reduction in dermal thickness. The size of the source varied from 0.1 to 40.0 mm in diameter; this covered the range of source sizes designed to simulate exposure to radioactive "hot" particles (< or = 1.0 mm diameter) up to the lower range of field size that patients may be exposed to in radiotherapy treatments. Radiation doses were measured using an extrapolation chamber with a collecting electrode of 1.1 mm2, and thus the quoted doses represent an average dose over this area. For the larger 90Sr/90Y sources of > or = 5 mm diameter and the larger 170Tm sources of > or = 2 mm diameter there was no evidence, based on levels of damage consistent with a > or = 10, > or = 20, > or = 30, and > or = 40% reduction in relative dermal thickness, for any effect of source size on the ED50 value for each of these specified levels of effect. However, there was a marked effect of beta-particle energy; the skin surface doses associated with the ED50 values (+/- SE) for a > or = 20% reduction in relative dermal thickness were approximately 12 and approximately 40 Gy for 90Sr/90Y and 170Tm, respectively. This difference in skin surface dose for an equivalent level of dermal injury reflects the variation in the depth dose from these two beta-particle emitters. These skin surface doses, for what was considered to be a clinically detectable dermal effect, were below the ED10 for the early skin response of moist desquamation. This supports the selection of late dermal thinning as the effect on which to base dose limits in radiation protection for more generalized larger area skin exposures. In comparison, single exposures to a small area, from sources designed to simulate those from hot particles, reinforced the view that acute ulceration should be the effect on which dose limitation is based. Either the isoeffect doses for a clinically detectable reduction in relative dermal thickness of > or = 20%, following a single exposure to a small area, were higher than the ED10 for acute ulceration or the area of skin showing dermal thinning was so small that it was not considered to be detrimental. PMID- 8451381 TI - Correlation of human longevity oscillations with sunspot cycles. AB - An examination of past human mortality trends revealed that the mean longevity of birth cohorts from 1740 to 1900 for United States of America (U.S.) Congressional Representatives exhibited oscillations that coincided with the 9- to 12-year sunspot cycle. Cohort mean longevities were 2-3 years greater during times of low sunspot activity than at peak activity. This phenomenon was confirmed in data from members of the House of Commons of the United Kingdom Parliament and from University of Cambridge alumni. An additional longevity oscillation with a longer period was visible in the data and may also be related to sunspot cycles. The amplitude and frequency modulations in the longevity and sunspot oscillations aligned when a 20-year phase shift was incorporated. This shift requires the existence of a lag between solar changes and the affected birth cohorts. Several possible causes of the effect are discussed, in particular: radiation on primordial germ cells in developing embryos; influenza epidemics and pandemics; and weather. The size of the longevity oscillation requires that the solar effect must be considered in studies that examine longevity trends and risk estimation. PMID- 8451382 TI - Survival of Chinese hamster V79 cells after irradiation with a mixture of neutrons and 60Co gamma rays: experimental and theoretical analysis of mixed irradiation. AB - Irradiation with a mixture of high-LET and low-LET radiation was investigated to determine whether the sequence of delivery had any effect. Survival of Chinese hamster V79 cells irradiated sequentially with neutrons (40%) followed by 60Co gamma rays (60%) did not differ from cells irradiated in the reverse order up to a total dose of 7.5 Gy, which indicated that the effect of mixed irradiation was independent of the sequence of delivery under the conditions adopted. These results imply that the Zaider-Rossi model of mixed irradiation, which predicts that the sequence of delivery has no effect, is superior to the additive damage model, which predicts that sequence has an effect. Based on these results, the Zaider-Rossi model was extended to fit various types of mixed irradiation (sequential and partially or completely simultaneous irradiation), and the experiments for sequential and completely simultaneous irradiations obtained by Higgins et al. (Radiat. Res. 95, 45-56, 1983) and McNally et al. (Int. J. Radiat. Biol. 45, 301-310, 1984) were simulated as detailed examples. Using this extended model, their contradictory results regarding cell survival following sequential and simultaneous irradiation were shown to be due to differences in the dose rate of the radiation delivered in each study. PMID- 8451383 TI - Effect of X rays alone or combined with diethylnitrosamine on tumor induction in infant mouse liver. AB - The possible combined effects of the initiator diethylnitrosamine (DEN) with X rays on cancer induction in C57BL/Cnb mouse liver were evaluated. Four groups of infant mice were treated as follows: with DEN alone, with X rays alone, with DEN + X rays, and with X rays + DEN. Mice in each group were killed at 10-week intervals over 70 weeks. The following parameters were measured: body weight, liver weight, number and size of macroscopic liver lesions, and number and total surface of the different types of microscopic liver lesions. The number of induced liver foci and carcinomas was found to depend essentially on the dose of DEN. X irradiation did not produce any combined effect on the induction of foci and carcinomas when given 7 days before or after DEN administration. PMID- 8451384 TI - Effect of UV-A on the linolenic acid micelles. AB - UV-A produced a dose-dependent linear increase of peroxidation in linolenic acid micelles as detected by the assay of (i) conjugated dienes, (ii) hydroperoxides, (iii) malondialdehyde (MDA), and (iv) the fluorescent adduct formed by the reaction of MDA with the amino acid, glycine. While sodium formate, dimethyl sulfoxide, superoxide dismutase, and ethylenediamine-tetraacetic acid produced no significant inhibition, some generally used singlet oxygen quenchers, beta carotene, dimethylfuran, L-histidine, and sodium azide, caused significant inhibition of the UV-A-induced peroxidation of the linolenic acid micelles. alpha Tocopherol and butylated hydroxytoluene produced more than 90% inhibition of the UV-A-induced peroxidation. ESR spectrometry revealed the formation of 2,2,6,6 tetramethylpiperidine oxide in the UV-A-irradiated aqueous solution of 2,2,6,6 tetramethylpiperidine. The involvement of singlet oxygen (1O2) in the UV-A induced peroxidation of linolenic acid micelles is discussed. PMID- 8451386 TI - Monoclonal gammopathy in atomic bomb survivors. AB - An analysis of monoclonal gammopathy in relation to radiation exposure was conducted on atomic bomb survivors examined between October 1979 and September 1981 and between June 1985 and May 1987. There was no overall increase in the relative risk of monoclonal gammopathy and only a suggestive increase in benign monoclonal gammopathy in the second survey which did not achieve statistical significance (P = 0.17). Thirty-one cases were detected among 8796 individuals studied in the first survey, whereas 68 cases were found among 7350 people in the second survey. Among the 31 cases found in the first survey, 9 individuals (29%) died before the second survey: 4 of cancer, 4 of vascular disease, and 1 of infection. Among the 8 individuals with benign monoclonal gammopathy examined in both surveys, 4 developed suppression of residual immunoglobulin(s), suggesting the progression of monoclonal gammopathy. The overall relative risks of monoclonal gammopathy in atomic bomb survivors in the two surveys were not significantly increased with increasing radiation dose. Only benign monoclonal gammopathy in 1985-1987 showed a suggestive increase with radiation exposure. The relative risk of benign monoclonal gammopathy in 1985-1987 was 2.64 in the group exposed to 0.01-0.49 Gy and 2.14 in the > or = 0.50-Gy group (95% confidence intervals = 0.90-8.82 and 0.69-7.31, respectively). PMID- 8451385 TI - Ratios of radiation-produced chromosome aberrations as indicators of large-scale DNA geometry during interphase. AB - Chromosome aberrations produced by ionizing radiation are assumed to develop from DNA double-strand breaks (DSBs) which interact pairwise. Stable chromosome aberrations that exemplify inter- and intra-chromosomal exchanges are, respectively, translocations and pericentric inversions. By comparing the number of these for each chromosome one can infer results on the randomness of DSB induction or exchange formation and on large-scale chromosome geometry. We analyze frequencies of translocations and pericentric inversions in lymphocytes from 38 A-bomb survivors, using G-banding. A total of 636 translocations and 102 pericentric inversions were found. The 636/102 ratio of translocations to pericentric inversions is approximately 14 times smaller than predicted by a random model, in general agreement with earlier results and results on the ratio of dicentrics to centric rings for in vitro irradiation. Presumably the excess of intra-chromosomal exchanges is due to a spatial proximity effect, implying a localization of chromosomes within the cell nucleus during and shortly after irradiation. The distribution of the pericentric inversions among different chromosomes indicates this proximity effect is roughly the same for all chromosomes, regardless of DNA content; i.e., the ratio of pericentric inversions for two different chromosomes approximately equals the ratio given by a model which takes into account chromosome lengths and centromere locations but otherwise assumes randomness. Possible exceptions are chromosomes 7 and 12, which show some excess of pericentric inversions. The percentage of translocations involving each chromosome corresponds roughly to the percentage expected assuming randomness, except that for chromosome 1 there is a significant excess. PMID- 8451387 TI - The inverse dose-rate effect for oncogenic transformation by charged particles is dependent on linear energy transfer. AB - Mouse C3H 10T1/2 cells were exposed to single or fractionated doses of charged particles of defined linear energy transfer (LET) from 25 to 200 keV/microns. Dose fractionation with prolonged time intervals enhanced the yield of transformed foci compared with a single acute dose for a range of LET values between 40 and 120 keV/microns. Radiations of lower or higher LET did not show the enhancement that is commonly referred to as the inverse dose-rate effect. The fractionation scheme that was used consisted of three dose fractions; the maximum enhancement of transformation occurred with an interval of 150 min between dose fractions. This inverse dose-rate effect, demonstrated for cycling cells in log phase, was not seen for cells in plateau phase. PMID- 8451388 TI - Mechanistic considerations on the dose-rate/LET dependence of oncogenic transformation by ionizing radiations. AB - When exposure to densely ionizing radiation is protracted, the resulting biological effect is sometimes, but not always, enhanced for transformational end points, relative to acute exposure. A pattern has emerged as to the dependence of this effect on dose, dose rate, and radiation quality. Previous calculations indicated that the dose and dose-rate trends can be predicted by a model in which there is a period within the cell cycle of very high sensitivity to oncogenesis. Recent experiments indicate that the inverse dose-rate effect is significant over a very limited range of LETs--from about 30 to 130 keV/microns. We discuss such LET effects in the context of cell cycle-dependent models, and suggest that the effects are understandable on the basis of such models. In essence, the inverse dose-rate effect disappears at high LET because of a reduction in the number of cells being hit, and disappears at LETs below about 30 keV/microns because most of the dose is deposited at low specific energies, insufficient to produce the saturation effect which is central to the phenomenon. At even lower LETs, damage repair yields the familiar sparing associated with protraction of X- or gamma-ray doses. PMID- 8451389 TI - Induction and repair of DNA double-strand breaks. AB - Induction and repair of DNA double-strand breaks (DSBs) was measured using a pulsed-field gel electrophoresis system. A cell line of methotrexate-resistant EMT-6 cells that contain numerous double-minutes (DMs) 3 million base pairs in size was employed. The electrophoretic mobility of these DMs depends on whether they have zero, one, or more than one DSB. With no DSBs the DMs remain as circles and are trapped in the origin of electrophoresis, but with one DSB the DMs migrate as a discrete band and can be detected easily through hybridization with a gene-specific probe. Using a clamped homogeneous electrical field apparatus, the induction of DSBs in the 1.5 to 12 Gy X-ray dose range is studied and is shown to be linear. Double-strand break repair following 7.5 Gy is studied, and is shown to be exponential. The kinetics of both induction and repair of DSBs induced in DM DNA was compared to the induction and repair of DSBs in chromosomal DNA and is shown to be similar. The kinetics of repair of DSBs following 7.5 Gy for cells embedded in agarose and cells in suspension is shown to be similar. PMID- 8451390 TI - Cancer mortality (1956-1985) among male employees of Atomic Energy of Canada Limited with respect to occupational exposure to external low-linear-energy transfer ionizing radiation. AB - The mortality experience between 1956 and 1985 of 8977 males employed by Atomic Energy of Canada Limited is reported. A total of 4260 men, 47% of the cohort, were exposed to low doses of external ionizing radiation at low dose rates, with a mean cumulative equivalent dose of 52.1 mSv. For cancers as a whole the excess relative risk, based on 227 deaths, was 0.36% per 10 mSv (90% confidence bounds 0.46, 2.45). This is quite comparable to the corresponding estimate based on the atomic bomb survivors study. There was a positive association between radiation dose and death from leukemia (excluding chronic lymphatic leukemia) P = 0.058. However, this was based on only four deaths and hence cannot sensibly be compared to estimates based on high-dose studies. The present results suggest that, for cancer as a whole, risk estimates based on high-dose studies are unlikely to underestimate risks substantially for low-dose and low-dose-rate exposures. PMID- 8451391 TI - Long-term effects on the thyroid of irradiation for skin angiomas in childhood. AB - Thyroid morphological and functional tests were carried out on 396 patients who were recalled because their thyroid gland had been exposed during hemangioma irradiation in childhood 11-43 years before (median, 22 years). The irradiations have been classified into two categories based on their duration: short duration, from a few seconds to a few minutes (90S and X rays), and long duration, from 30 min to several hours (336Ra, 192Ir, and 32P). The risk of a thyroid nodule increased significantly with the total dose received by the thyroid; it was linked to the dose delivered in the short duration (excess relative risk per Gy = 10), but not to that delivered in the long duration. The risk of a simple diffuse goiter, which also increased with the dose received by the thyroid, did not depend on the duration of the irradiation. In conclusion, this study emphasizes the role of the dose rate in the risk of thyroid nodule, the detection of which does not appear to be improved by plasma thyroid marker determination. PMID- 8451392 TI - Relative effectiveness of mixed radiation fields. AB - For all one-hit detectors the relative effectiveness of a mixed radiation field may be found as the dose-weighted average of the relative effectiveness of its components, segregated according to the atomic number Z and the energy T. We emphasize that this procedure is incorrect for mammalian cells, whatever the nature of the segregation. PMID- 8451393 TI - What does the mean inactivation dose characterize? PMID- 8451394 TI - Modern imaging of the pituitary. PMID- 8451395 TI - Percutaneous enteral alimentation: gastrostomy versus gastrojejunostomy. AB - Scintigraphy was used to detect gastroesophageal reflux, determine whether percutaneous gastrostomy (PG) tubes cause reflux, and help in the choice between PG tubes versus percutaneous gastrojejunostomy (PGJ) tubes. During a 2-year period, 46 patients were evaluated with scintigraphy immediately before and 1 week after PG tube placement. Findings in the pre- and postplacement reflux studies were the same in 39 patients (85%). Proof of reflux on either study was considered an indication for conversion to the PGJ tube; at least one study was positive for reflux in 21 patients (46%). All patients were followed up for tube complications, pneumonia, and cause of death. During follow-up, six of 24 patients correctly maintained with PG tubes (25%) and 18 patients with PGJ tubes (39%) developed pneumonia, the cause of death in four of 24 patients with PG tubes (17%) and five of 18 patients with PGJ tubes (28%). The PG tube does not induce reflux, and scintigraphy is useful in selection of patients who can be safely maintained with the PG tube without an increase in the morbidity or mortality associated with reflux and aspiration. PMID- 8451396 TI - Cleansing enema prior to double-contrast barium enema examination: is it necessary? AB - In a prospective study, 443 patients referred for double-contrast barium enema examination were allocated to one of four regimens consisting of either 24 or 48 hours of clear liquids in combination with a cathartic laxative (magnesium sulfate), an irritant laxative (bisacodyl), and hydration. One regimen from each time group included a preliminary cleansing enema. Significantly higher bowel cleanliness scores were given to the 48-hour regimen with no cleansing enema (P < .0002). Scores for overall quality of the barium enema examination (based on detectability of a 1-cm lesion) showed no significant differences between a 24- and a 48-hour regimen, with or without a cleansing enema. No differences emerged in patient acceptance of the regimens, and 54%-57% of patients had no complaints about the preparation. The authors recommend a 48-hour preparation to minimize the risk of interfering fecal material, especially in subjects with colonic dysmotility. A time-consuming cleansing enema can be omitted. PMID- 8451397 TI - Focal nodular hyperplasia of the liver: value of color Doppler US in association with MR imaging. AB - Seventeen patients with 19 lesions of focal nodular hyperplasia (FNH) underwent prospective examination with color Doppler ultrasound (US) and magnetic resonance (MR) imaging. In 13 lesions, color Doppler US demonstrated central spots with an arterial Doppler spectrum. The frequency shifts ranged from 1.02 to 1.94 kHz (mean, 1.56 kHz). On flow-sensitive unenhanced gradient-echo images, hyperintense central dots were depicted in only five of these 13 lesions. All the MR features of FNH were present in 12 lesions. Among the seven lesions without all of the MR features, central color spots were present with an arterial Doppler spectrum in four lesions. In the remaining three lesions, color Doppler examination demonstrated either peritumoral pulsatile flow (two lesions) or no flow (one lesion). Color Doppler US adds information about the intratumoral flow characteristics of this vascular malformative lesion and appears to be superior to MR imaging in detection of the arterial intratumoral abnormalities. PMID- 8451398 TI - Hepatic parenchymal changes after intraarterial Y-90 therapy: CT findings. AB - The serial contrast material-enhanced computed tomographic scans of 23 patients treated with intraarterial yttrium-90 microspheres as therapy for hepatic metastatic disease were reviewed for evidence of parenchymal changes in the liver in areas not involved with tumor. Irregular low-attenuation geographic areas that developed in the hepatic parenchyma after therapy were graded as mild, moderate, or severe and were evident in 12 of 23 patients. In nine cases of mild to moderate changes in the hepatic parenchyma, the abnormality was either focal or asymmetric. In all three patients receiving the highest dose (15,000 cGy), severe diffuse parenchymal changes were seen in all hepatic segments. In the remaining 11 patients, no parenchymal changes were seen. The most pronounced changes were seen at 8 weeks after therapy and were partially or completely reversible at 16 24 weeks. All patients had minimal or no change in liver function and no clinical sequelae attributable to liver injury. PMID- 8451399 TI - Thickened endometrium in the postmenopausal woman: sonographic-pathologic correlation. AB - A correlative sonographic and histopathologic analysis was performed in 35 postmenopausal women with greater than 5-mm thickening of the endometrium at pelvic sonography. Women undergoing estrogen replacement were excluded from study. Four distinct sonographic patterns were encountered. Pattern 1 consisted of echogenic endometrium with small cysts (endometrial polyp with cystic hyperplasia [n = 9], atrophic endometrium with cystically dilated glands [n = 5], and atrophic endometrium [n = 3] at microscopic examination). Pattern 2 was homogeneous echogenic endometrium (proliferative endometrium [n = 3] and adenomyomatous polyp [n = 1]). Pattern 3 was irregular, inhomogeneous endometrium with ill-defined hypoechoic areas (endometrial carcinoma [n = 5], complex hyperplasia with atypia [n = 1], blood clots [n = 1], and atrophic endometrium with eosinophilic metaplasia [n = 1]). Pattern 4 was thin endometrium with fluid in the endometrial cavity (scant atrophic endometrium [n = 6]). Thus, an endometrial thickness of greater than 5 mm in postmenopausal women is associated with a variety of pathologic conditions. Subclassification of sonographic patterns may be helpful in differentiating benign cystic atrophy or cystic endometrial hyperplasia from malignant endometrial lesions. PMID- 8451400 TI - Assessment of incontinence with intraurethral US: preliminary results. AB - To explore the usefulness of intraluminal ultrasound (US) for diagnostic imaging of the female urethra, 22 female patients with different degrees of urinary incontinence and 10 female patients with normal continence underwent examination by means of a 20-MHz intravascular US system. Contiguous sections were used for three-dimensional reconstructions on a personal computer-based system in two patients. The circumference and area of the internal urethral sphincter were measured in all patients; the measurements were obtained by means of manual delineation of the inner and outer contours of the sphincter. A correlation was found between (a) area and circumference and (b) the degree of incontinence (P < .01). No patient with normal urinary continence showed a reduced sphincter size (a circumference smaller than 2.8 cm). Intraurethral US, which yields images of the urethra and surrounding tissues, may become an important adjunct to urethrography and functional methods (assessment of urodynamics) for the diagnostic evaluation of incontinence. PMID- 8451401 TI - Bladder tumors: staging with gadolinium-enhanced oblique MR imaging. AB - To clarify the importance of imaging plane in evaluation of invasion by tumor into muscle, 50 patients with bladder tumors underwent examination with magnetic resonance (MR) imaging performed with an oblique plane and the early phase of contrast enhancement. After the ideal oblique plane was selected, an oblique T2 weighted image was obtained. Gadopentetate dimeglumine was then administered, and an oblique T1-weighted image was obtained. The staging based on oblique T2 weighted and oblique contrast material-enhanced T1-weighted MR images was then correlated with histopathologic staging. The respective accuracies of oblique contrast-enhanced T1-weighted and oblique T2-weighted images were 78% and 60% for overall staging (P < .05), 90% and 74% for differentiation between (a) stage T1 and lower-stage tumors and (b) stage T2 and higher-stage tumors (P < .05), and 92% and 88% for differentiation between (a) stage T2 and lower-stage tumors and (b) stage T3a and higher-stage tumors (P > .05). Oblique MR imaging performed in conjunction with the early phase of contrast enhancement showed significantly high staging accuracy, especially in differentiation between superficial tumors and tumors with superficial muscle invasion. PMID- 8451402 TI - Pancreatic biopsy: striving for excellence. PMID- 8451403 TI - Bladder wall morphology: in vitro MR imaging-histopathologic correlation. AB - To study the morphology of the normal and inflamed bladder wall, the findings of magnetic resonance imaging and histopathologic examination of 13 in vitro specimens were correlated. Normal bladder wall appeared as a band of intermediate signal intensity on T1-weighted images and as bands of low (inner) and intermediate (outer) signal intensity on T2-weighted images. Inflamed bladder walls demonstrated two additional inner bands of intermediate (inner) and high (innermost) signal intensity on T1-weighted images and high (inner) and low (innermost) signal intensity on T2-weighted images. The mean histopathologic percentages of muscle bundles in inner and outer bands that appeared on T2 weighted images were 92.5% +/- 4.9 and 78.3% +/- 8.2, respectively. The authors conclude that the total thickness of the two bands of differing intensity that appeared on the T2-weighted images of the normal bladder wall correlated well morphometrically with the muscle layers in the histopathologic specimens, and that the different signal intensities in the muscle layer represent a compact inner and looser outer arrangement of smooth muscle bundles. PMID- 8451404 TI - Incidental vesicoureteral reflux in neonates with antenatally detected hydronephrosis and other renal abnormalities. AB - Postnatal imaging findings were reviewed in 130 neonates and young infants referred for imaging evaluation of antenatally detected renal abnormalities. All children underwent voiding cystourethrography and upper urinary tract imaging with sonography and/or renal scintigraphy. Vesicoureteral reflux was present in 49 patients (38%) and was bilateral in 24. All grades of reflux were observed. Reflux occurred in 41 of 98 neonates (42%) in whom postnatal imaging revealed persistent upper tract abnormalities (eg, hydronephrosis, cysts, renal agenesis) and in eight of 32 (25%) with normal findings at postnatal sonography and/or renal scintigraphy. Reflux was the single most common urologic diagnosis and was the only postnatal abnormality in 12 patients (9%). The authors conclude that neonates with antenatally detected hydronephrosis should be routinely screened for reflux with voiding cystography. Detection and aggressive management of reflux in the asymptomatic neonate in whom renal growth and function are unimpaired theoretically offer the best opportunity for preventing renal injury later in childhood. PMID- 8451405 TI - Impact of contrast medium temperature on bladder capacity and cystographic diagnosis of vesicoureteral reflux in children. AB - To assess the influence of temperature of contrast medium used in voiding cystourethrography (VCUG) on the estimation of bladder capacity and detection of vesicoureteral reflux (VUR), 250 consecutive children (aged from birth to 13.5 years) undergoing VCUG were randomized to receive room temperature (n = 133) or body temperature (n = 117) contrast medium. Bladder capacity (ie, volume infused) was measured, and bladder volume index (BVI) was calculated by dividing the measured capacity by the predicted capacity. Contrast medium temperature did not affect either bladder capacity (warm: mean capacity, 210.8 mL; cold: mean capacity, 212.6 mL) or BVI (warm: mean BVI, 1.15; cold: mean BVI, 1.10). Although boys had smaller capacities than girls, neither capacity nor BVI was significantly (P > .05) affected by contrast medium temperature in either sex. VUR was detected in 42 (35.9%) of 117 children studied with warmed contrast medium and in 42 (31.6%) of 133 studied with room temperature medium. Prevalence of VUR was unaffected by contrast medium temperature in children with previously diagnosed VUR and in those studied for the first time. PMID- 8451406 TI - Anatomic features of reduced-size liver transplant: postsurgical imaging characteristics. AB - In this retrospective review, the authors evaluated the anatomic and imaging features of 140 reduced-size liver transplants in 120 boys and girls; 100 of these patients (83.3%) were 2 years old or younger. The authors reviewed the surgical reports, plain radiographs, contrast material-enhanced studies of the gastrointestinal tract, duplex Doppler and color Doppler ultrasound (US) scans, and computed tomographic (CT) scans. Understanding the anatomic features associated with transplantation was crucial to understanding the post-surgical imaging characteristics. Changes in visceral anatomic structure caused a variety of imaging appearances, some of them misleading: (a) Some patients had unusual bowel gas patterns on plain radiographs because of a shift in location by bowel loops; (b) gastrointestinal studies showed gastric compression by an oversized left lobe that mimicked mass effect; and (c) displacement or migration of the duodenum, jejunum, or cecum into the right hepatic fossa sometimes mimicked malrotation. Pitfalls were created by fluid and gas collections at the transected edge. US and CT were often used to further assess anatomic structures after surgery; color Doppler was especially helpful in vascular localization. PMID- 8451407 TI - Neonatal vesicoureteral reflux: what do we know? PMID- 8451408 TI - Indirect trauma to the growth plate: results of MR imaging after epiphyseal and metaphyseal injury in rabbits. AB - Abnormalities of the growth plate secondary to epiphyseal and metaphyseal injury were studied with magnetic resonance (MR) imaging, radiography, and histologic examination in 20 rabbits. Epiphyseal injury resulted in either the formation of a bony bridge across the growth plate or focal curving of the growth plate caused by a decrease in longitudinal growth. Metaphyseal injury resulted in interference with endochondral ossification, thickening of the growth plate, and extension of cartilage into the metaphysis. Serial MR images obtained during the first 6 weeks after injury showed persistence of abnormalities of the growth cartilage after epiphyseal injury, but resolution of abnormalities after metaphyseal injury. Abnormalities of the cartilage were best seen on T2-weighted images. Gadolinium enhancement showed reconstitution of metaphyseal vascularity after metaphyseal injury but did not enable detection of transphyseal vascularity after epiphyseal injury until a bony bridge formed. PMID- 8451409 TI - Enhancement of joint fluid with intravenously administered gadopentetate dimeglumine: technique, rationale, and implications. AB - This study reports findings on joint fluid enhancement after intravenous administration of gadopentetate dimeglumine. Ten subjects were studied: two asymptomatic volunteers and eight patients with suspected meniscal tears. The subjects underwent imaging at 1.5 T before, immediately after, and 42-60 minutes after intravenous administration of gadopentetate dimeglumine. The rate of fluid enhancement was assessed in three subjects, and the effects of exercise were studied. All subjects exhibited enhancement of joint fluid. Mean fluid enhancement for patients was 137% on initial and 262% on delayed images obtained after exercise. Exercise increased the rate and degree of fluid enhancement and distributed contrast material uniformly throughout the joint. The arthrographic effect of the fluid enhancement increased the number of perceived cartilage defects. This study documents enhancement of joint fluid in healthy subjects and in those with effusions. The arthrographic effect may provide a more convenient alternative to intraarticular injection of gadopentetate dimeglumine for MR arthrography. PMID- 8451410 TI - Anatomic features of the carpal scaphoid: validation of biometric measurements and symmetry with three-dimensional MR imaging. AB - The goals of reconstructive surgery for scaphoid fracture nonunions include restoration of normal scaphoid length and shape by use of the contralateral scaphoid bone as a geometric model. A literature search revealed limited documentation of normal biometric measurements and no validation of scaphoid anatomic symmetry. A study was performed to provide normative data and evaluate the right-to-left symmetry of specific geometric measurements of the scaphoid. One hundred normal carpal scaphoid bones in 30 healthy subjects and 40 patients were examined with three-dimensional magnetic resonance (MR) imaging. Standardized oblique projections were reconstructed from each three-dimensional data set, and seven biometric measurements of each scaphoid were obtained. Normative data from the study group were obtained by means of analysis of all 100 scaphoids. Right-to-left symmetry was validated with the biometric measurements of both scaphoids in the healthy subjects. These data validate scaphoid symmetry and provide 95% confidence intervals for specific biometric measurements that are used for preoperative planning of surgical reconstruction of scaphoid nonunions. PMID- 8451411 TI - Ectopic pregnancy: evaluation with endovaginal color Doppler flow imaging. PMID- 8451412 TI - Role of SPECT in differentiating malignant from benign lesions in the lower thoracic and lumbar vertebrae. AB - The authors categorized 125 spinal lesions in cancer patients and 127 lesions in patients with back pain according to their location in the vertebra on single photon emission computed tomographic (SPECT) images. Forty-four lesions were metastases, all in patients with known malignancy. Lesions in the apophyseal joints were all benign. Lesions manifesting as abnormal uptake projecting beyond the vertebral body surface were osteophytes. Thirty-seven percent of the lesions detected in cancer patients were categorized in either of these two benign categories. Lesions showing focal or diffuse uptake in the body were usually benign (96% and 87%, respectively). Lesions showing uptake in the body and pedicle were usually metastases (83%). When abnormal uptake was seen in both the body and posterior elements but with an intervening normal pedicle, benign disease was the most common cause (93%). It was concluded that the location of lesions on tomographic images provides useful information for differentiation between malignant and benign lesions in the vertebrae. PMID- 8451413 TI - Early-stage avascular necrosis of the femoral head: MR imaging for prognosis in 31 cases with at least 2 years of follow-up. AB - Thirty-one cases of stage 1 or 2 osteonecrosis (ON) of the hip in 27 patients were studied with T1-weighted coronal magnetic resonance (MR) imaging. Three quantitative parameters were measured on the contiguous MR sections, corresponding to the 2-cm-wide median portion of the femoral head: the angle filled by ON (alpha), the percentage of weight-bearing femoral cortex involved with ON (WB), and the percentage of femoral head surface involved with ON. The clinical and radiologic courses were assessed after at least 2 years of follow-up (mean, 46 months). Core decompression was performed in 12 cases of ON. Values were strikingly lower in the group with good clinical or radiologic outcome versus poor outcome, with very little overlapping. WB was the more reliable parameter. Outcome of hips treated with versus without core decompression appeared closely related with these MR parameters and not with the treatment procedure. Thus, a quantitative approach to determination of extent and location of the lesion on the initial MR image appears accurate for use in the prediction of long-term outcome of ON. Effectiveness of core decompression should be reevaluated on this basis. PMID- 8451414 TI - Diagnosis of ectopic pregnancy with endovaginal color Doppler US. PMID- 8451415 TI - Patellar tracking patterns during active and passive knee extension: evaluation with motion-triggered cine MR imaging. AB - To evaluate the critical range of the patellofemoral joint motion from 30 degrees of knee flexion to full extension, motion-triggered cine magnetic resonance (MR) imaging was performed during active extension in 13 patients with confirmed patellar maltracking and 15 healthy subjects. Cine MR images were compared with static MR images obtained during incremental extension of the knee joint. To evaluate the patellar tracking pattern, the same imaging parameters (patellar tilt angle, bisect offset, and lateral patellar displacement) and section locations were used in the static and motion-triggered studies. Statistically significant differences between the passive and active knee motions were found in all three parameters in the group of patients and in the bisect offset in the control group. The comparison between patients and healthy subjects yielded statistically significant differences for all parameters in actively extended knees but not in passively extended knees. The results demonstrate the importance of dynamic patellar motion studies for diagnosis of patello-femoral maltracking. PMID- 8451416 TI - Denervated human skeletal muscle: MR imaging evaluation. AB - Because determination of neurologic integrity after severe limb trauma is crucial in patient care, the authors assessed magnetic resonance (MR) imaging as a tool to map denervated motor units of skeletal muscle in patients with traumatic peripheral neuropathy. Denervation was confirmed in 22 patients with use of electromyography, surgery, or both. MR imaging was performed with moderately T1- and T2-weighted spin-echo and short-tau inversion-recovery (STIR) sequences. MR imaging was unreliable in depicting acute denervation. Muscles of patients with subacute denervation had prolonged T1 and T2, which contributed to conspicuous hyperintensity on STIR images. Chronically denervated muscles showed marked atrophy, variable changes on STIR images, and conspicuous fatty infiltration on T1-weighted images. Normal variants in motor unit anatomy were seen in denervated muscle volumes outside the expected distribution of the injured nerve. MR imaging is promising for the noninvasive mapping and monitoring of denervated muscle in subacute and chronic phases of peripheral neuropathy. PMID- 8451417 TI - Absolute concentrations of metabolites in the adult human brain in vivo: quantification of localized proton MR spectra. AB - In vivo concentrations of cerebral metabolites were obtained by means of 52 single-voxel, localized proton magnetic resonance (MR) spectroscopic examinations of different regions of the brain performed in 26 healthy adults aged 21-32 years. The study was performed at 2.0 T with use of a circularly polarized head coil to ensure homogeneous radio-frequency excitation and signal reception. Proton MR spectra were obtained in the stimulated-echo acquisition mode under fully relaxed conditions (repetition time > or = 6,000 msec) and at short echo times (20 msec) to minimize corrections due to T1 and T2 attenuation and depict the spectra of metabolites with strongly coupled resonances. Absolute concentrations were obtained by means of calibration of resonance signal areas with those of pertinent metabolite solutions from separate studies and correction for coil loading and partial volume effects (eg, with perfused capillary networks and cerebrospinal fluid). The results provide a quantitative basis for studies of both normal human neurochemistry in vivo and metabolic alterations in diseases of the brain. PMID- 8451418 TI - Anterior pituitary gland in pregnancy: hyperintensity at MR. AB - The authors obtained midline sagittal T1-weighted magnetic resonance images of the pituitary gland in 30 female patients: five pregnant; two postpartum; and 23 nonpregnant, of childbearing age, and without evidence of pituitary gland disorder. In pregnant and postpartum patients, the relative signal intensity of the anterior lobe compared with the pons was statistically higher than that in the control group (P < .001). In the pregnant patients, positive correlation was noted between the signal intensity ratio of the anterior lobe and the pons and gestational age. The authors believe that the hyperintensity of the anterior pituitary lobe in pregnant and postpartum patients is a physiologic variation. Because the anterior lobe of an infant may also be hyperintense on T1-weighted images and because the anterior lobes of an infant and a pregnant woman are histologically similar, the mechanism responsible for the hyperintensity in each case may be the same. It is important to know that the anterior lobe may be hyperintense in pregnant or postpartum women, especially in cases of probable pituitary gland abnormality accompanying pregnancy, such as pituitary hemorrhage, Sheehan syndrome, or lymphocytic adenohypophysitis. PMID- 8451419 TI - Mycobacterium avium-intracellulare complex: evaluation with CT. AB - Pulmonary Mycobacterium avium-intracellulare (MAI) complex has been reported with increasing frequency, but computed tomographic (CT) evaluation of pulmonary MAI complex has been seldom reported. The authors retrospectively reviewed chest CT examinations performed in 62 patients with positive MAI cultures within 1 month of CT. Of the 62 patients, 40 had bronchiectasis and 60 had infiltrates, usually of the nodular variety (39 patients). All 35 patients with small nodular infiltrates had bronchiectasis. These 35 patients did not have concurrent malignancy or clinical evidence of immunocompromise, and 29 (83%) of them were women (mean age, 66 years). Of the 27 patients without small nodular infiltrates and bronchiectasis, 25 had underlying malignancy or immunocompromise. The predominance of older women without underlying malignancy or immunocompromise but with findings of small nodular infiltrates and bronchiectasis at chest CT may indicate such patients to be a subtype of patients with pulmonary MAI complex. PMID- 8451421 TI - Lumbar cribriform fascia: appearance at freezing microtomy and MR imaging. AB - Axial T1-weighted magnetic resonance (MR) images and exactly corresponding sections obtained with freezing microtomy of cadaveric lumbosacral spinal columns were compared to describe the MR appearance of the cribriform fascia within the neural foramen. On anatomic sections, the cribriform fascia was identified as a thin sheet of tissue in the lateral neural foramen. On MR images, the cribriform fascia appeared as a thin band of low signal intensity, which contrasted with the high-signal-intensity epidural fat. The cribriform fascia is another landmark in the neural foramen that can be identified with MR imaging. PMID- 8451420 TI - Progressive multifocal leukoencephalopathy in 47 HIV-seropositive patients: neuroimaging with clinical and pathologic correlation. AB - The authors investigated the spectrum of radiologic findings in a large series (n = 47) of patients seropositive to human immunodeficiency virus (HIV) 1 and with pathologically proved progressive multifocal leukoencephalopathy, to determine the characteristic imaging pattern of the disease. Thirty-six computed tomographic (CT) scans and 29 magnetic resonance (MR) imaging studies obtained in the 47 patients were retrospectively reviewed and correlated with pathologic and clinical findings. Contrast agents were used in 32 CT procedures and 13 MR imaging studies. Lesions typically were hypoattenuating on CT scans and were characterized by areas of increased signal intensity without mass effect on dual echo MR images. Lesions most often involved periventricular and subcortical white matter in parietooccipital or frontal lobes. Fifteen patients had posterior fossa lesions, and disease was limited to the posterior fossa in two. Lesions were also in the corpus callosum (seven patients), thalamus (eight patients), and basal ganglia (seven patients). In comparison with CT, MR imaging demonstrated greater sensitivity for the extent and number of lesions. PMID- 8451422 TI - Central venous occlusion: MR angiography. AB - The authors evaluated time-of-flight magnetic resonance (MR) angiography in 30 patients with suspected thoracic venous occlusion. The results of the MR studies were compared with results at contrast venography in 22 patients and at central venous cannulation in seven of the remaining eight patients. Twenty-eight patients had abnormalities on MR venograms; 21 of these abnormalities involved multiple veins. Eight patients had superior vena cava (SVC) occlusion with retrograde azygos blood flow, and two patients had nonocclusive SVC thrombus. Fifteen patients had thrombosis involving the brachiocephalic veins; 14, involving the subclavian veins; and eight, involving the internal jugular veins. Correlation was excellent between findings of venous obstruction and occlusion at contrast venography and MR angiography. MR imaging provided more comprehensive information than catheter venography on central venous anatomy and blood flow. For evaluation of central veins, MR angiography is an accurate and graphic technique that may succeed in cases in which other methods may give inadequate findings or may be impossible to perform. PMID- 8451423 TI - Blood flow in the portal vein: velocity quantitation with phase-contrast MR angiography. AB - Quantitative phase-contrast magnetic resonance (MR) angiography of the portal vein was prospectively evaluated in 79 fasting patients and 23 healthy volunteers. Images were obtained during a 12-second breath-hold acquisition in the coronal (n = 102) and axial (n = 11) planes. Pathologic correlation was available in 55 of 79 patients and included findings of cholangiocarcinoma, cirrhosis, hepatocellular carcinoma, hepatitis, and metastatic disease. Forty-one patients had correlative Doppler ultrasound (US) findings. MR and US findings correlated as to flow direction in all cases. In nine patients, Doppler US velocity measurements were available and closely correlated with MR findings. A comparison of axial and coronal portal venous phase-contrast measurements in 11 patients revealed no substantial difference with regard to the plane used. Quantitative phase-contrast MR angiography is a simple and rapid technique for the assessment of portal venous patency, flow direction, and flow velocity and, combined with high-resolution conventional MR imaging, may obviate the current use of both computed tomographic and US examinations. PMID- 8451425 TI - Left ventricular measurements with cine and spin-echo MR imaging: a study of reproducibility with variance component analysis. AB - The authors studied the reproducibility of repeated measurements of left ventricular volumes, weight, and wall stress as determined with cine and spin echo magnetic resonance (MR) imaging. Two observers analyzed 40 serial MR imaging examinations twice, yielding a total of 160 repeated measurements. Estimates of 95% ranges for change were ejection fraction, 10% and 12%; wall mass, 16% and 21%; and wall stress, 22% and 20%, for measurements derived from cine MR imaging and spin-echo MR imaging, respectively. Reproducibility was not significantly different between cine and spin-echo MR imaging. Intraobserver, interobserver, and interexamination errors were quantitated with variance component analysis. Interexamination variability was the single most important contributor to total variance. Reproducibility of left ventricular chamber volume measurements with MR imaging is superior to that of other imaging modalities. In addition, MR imaging can provide reliable estimates of wall mass and wall stress. Efforts to improve reproducibility should be aimed at lowering interexamination variability. PMID- 8451424 TI - Incompatibility of Isovue 370 and papaverine in peripheral arteriography. AB - Complete thrombotic occlusion of the arterial blood flow in the upper extremity was produced after mixture of Isovue 370 (iopamidol) and papaverine hydrochloride during routine angiography. Bolus and then continuous infusion of urokinase failed to dissolve the thrombus. The patient required a surgical thrombectomy and recovered uneventfully. This case report demonstrates that caution should be exercised when Isovue 370 and papaverine are used in angiography. PMID- 8451426 TI - Hemostatic protein polymer sheath: improvement in hemostasis at percutaneous biopsy in the setting of platelet dysfunction. AB - To study the effectiveness of the protein polymer sheath (PPS), a device intended to limit hemorrhage caused by percutaneous biopsy, in the setting of platelet dysfunction (which may be an important cause of such hemorrhage), percutaneous biopsies were performed in eight anesthetized pigs: four control pigs and four pigs treated with the experimental aspirinlike drug venopirin. These biopsies were performed with (a) a cutting needle only, (b) the cutting needle equipped with the PPS, and (c) the cutting needle equipped with a thrombin-coated PPS. Needle configuration and biopsy site were randomized. Blood loss associated with each needle configuration was measured and compared with that associated with the other configurations. Venopirin caused a statistically significant increase in blood loss with all needle configurations. The PPS significantly reduced blood loss in both the control pigs and those treated with venopirin (P < .05); thrombin coating was a statistically significant factor only in the venopirin treated pigs. PMID- 8451427 TI - Normal trachea during forced expiration: dynamic CT measurements. AB - The purpose of this study was to define the range of normal intrathoracic tracheal diameters and cross-sectional areas during forced respiration. A report of tracheomalacia is also presented. Ten volunteers were studied in the supine position with dynamic computed tomography (CT), at a level at or between the brachiocephalic vein and the aortic arch, with 3-mm collimation and with image reconstruction by means of a high-spatial-frequency algorithm. Ten 100-msec dynamic scans were obtained at 500-msec intervals during a 6-second period as the patient performed forced inspiration and expiration vital capacity maneuvers. The mean cross-sectional area of the trachea decreased dynamically from 280 mm2 at end inspiration (standard deviation, 50.5; range, 221-388 mm2) to 178 mm2 at end expiration (standard deviation, 40.2; range, 115-236 mm2; P < .001) (mean decrease, 35% between inspiration and expiration; standard deviation, 18%; range, 11%-61%). The percentage decrease in cross-sectional area of the trachea correlates well with the decrease in the anteroposterior and coronal diameters of the trachea from maximum inspiration to maximum expiration (r = .879 and .916 and P = .0018 and .0002, respectively). PMID- 8451428 TI - Insufficient dialysis shunts: improved long-term patency rates with close hemodynamic monitoring, repeated percutaneous balloon angioplasty, and stent placement. AB - Over 54 months, 70 short stenoses of 63 shunts (32 Brescia-Cimino fistulas, 31 grafts) in 59 patients necessitated a first percutaneous transluminal angioplasty (PTA). Restenosis led to 63 redilations in 38 lesions. Nine stents were inserted in seven grafts and two proximal veins in seven patients, the indication being that stenosis had recurred twice in 6 months. In three of these stenoses, five delayed intrastent redilations were necessary. Three previously dilated occluded grafts were recovered with local thrombolysis. Morbidity was 4.08%, with one immediate rupture, four delayed pseudoaneurysms (1-28 months), and two periprocedural bacteremias. Half (15 of 29) of graft stenoses and only 14% (four of 27) of Brescia-Cimino fistula stenoses had a mean restenosis interval of less than 6 months. The mean restenosis interval increased from 3.6 months +/- 0.5 (standard deviation) before stent placement to 15.2 months +/- 0.4 after stent placement (P < .001). Insertion of a stent can be advised when stenoses of graft venous anastomoses have recurred twice in less than 6 months. The combination of all interventional radiologic procedures allowed a significant improvement in secondary patency rates after PTA, with 82% at 1 year, 79% at 2 years, and 71% at 3 years. PMID- 8451429 TI - Readability of informed consent forms for use with iodinated contrast media. AB - Informed consent forms used before intravenous administration of contrast media by both private practice (Pennsylvania Blue Shield) and academic (Association of University Radiologists) physician groups were analyzed to evaluate for readability and content. Most of the 160 consent forms required at least a high school education to be understood; 10 (6%) required a college education. Consent forms from academic institutions tended to be longer and contain more problems with sentence structure than those from private practice. Consent forms from both groups tended to have a weak, wordy writing style. Although most of the consent forms discussed at least some of the potential adverse reactions from intravenous contrast media, 37 (23%) made no mention of any potential adverse reaction. Indeed, 25 (16%) made no mention of contrast media at all. Only 12 (8%) consent forms included a discussion of nonionic contrast media. The authors provide sample consent forms that cover the common risks of ionic and nonionic contrast media and describe the availability of nonionic contrast media; these forms are understandable by an individual reading at only an eighth-grade level. PMID- 8451430 TI - MR imaging of silicone breast implants: comparison of different coil arrays. AB - To determine the optimal coil and patient position for magnetic resonance imaging of patients with silicone breast implants, images obtained with body, circular surface, flexible, single shoulder, and dual shoulder coils in various numbers of patients were compared with regard to signal-to-noise ratio (S/N), decay of signal intensity, resolution, and key area coverage. Images obtained with the dual shoulder coil and prone position, with a customized positioning device, gave the best S/N, resolution, and coverage of the breasts and axillae. PMID- 8451431 TI - Measuring masses on cross-sectional images. PMID- 8451432 TI - Chest wall invasion by bronchogenic carcinoma: evaluation with MR imaging. AB - The value of magnetic resonance (MR) imaging and the roles of various pulse sequences and contrast medium enhancement in detection of chest wall invasion were evaluated in 34 patients with primary bronchogenic carcinoma. Results were correlated with clinical data and computed tomographic studies. MR imaging criteria of parietal invasion included signal intensity identical to that of the tumor on T1-weighted images, intraparietal hyperintense signal of the tumor on T2 weighted images, and intraparietal enhancement with T1-weighted imaging and gadoterate meglumine administration. Twenty patients had parietal involvement, and MR imaging was positive in 18 of the 20 (sensitivity, 90%). Two false positive errors occurred among the 14 patients without parietal involvement (specificity, 86%). T2-weighted sequences had a sensitivity of 65% (11 of 17 cases). Contrast-enhanced and non-contrast-enhanced T1-weighted sequences had the same sensitivity, but contrast medium uptake was revealed in two patients without parietal involvement. Good spatial resolution appears to be the main factor for detection of parietal invasion. PMID- 8451433 TI - Tumor invasion of the chest wall in lung cancer: diagnosis with US. AB - The accuracies of ultrasonography (US) and computed tomography (CT) for determining tumor invasion of the chest wall in lung cancer were compared in a retrospective study of 120 patients. US findings were evaluated preoperatively according to the following criteria: disruption of pleura, extension through the chest wall, and fixation of tumor during breathing. CT findings were evaluated with the following criteria: obtuse angle of the mass to the pleural surface, more than 3 cm contact with the pleural surface, and visible pleural thickening associated with the mass. Chest wall invasion was judged as positive when at least two of the three findings were present with either technique. Nineteen of the 120 patients had chest wall invasion by tumor. The sensitivity of US was 100% and the specificity was 98%. The sensitivity of CT was 68% and the specificity was 66%. The accuracy of US and CT were 98% and 67%, respectively. PMID- 8451434 TI - Precision electrocautery excision of pulmonary lesions (Perelman technique): radiologic features. AB - The authors describe the radiologic features of precision electrocautery excision of pulmonary lesions (Perelman technique). Thin-walled cavities were seen on chest radiographs obtained in three patients at the site of the resected lesion subsequent to this surgical procedure. Knowledge of these findings can avoid a false diagnosis of abscess, septic emboli, or additional metastasis. PMID- 8451435 TI - Acute chest syndrome in sickle cell disease: CT evidence of microvascular occlusion. AB - Patients with sickle cell disease often develop acute chest syndrome (ACS). Signs of ACS include chest pain, fever, prostration, and pulmonary opacities. Pneumonia and infarction have been implicated in the pathogenesis of this syndrome. Infarction as a result of microvascular occlusion and pneumonia are not easily differentiated with chest radiography or ventilation-perfusion scintigraphy. The authors evaluated the ability of thin section (3-mm) chest computed tomography (CT) to help diagnose microvascular occlusion in ACS and thus help differentiate two of its most likely causes. CT scans of the chest of 10 patients with moderate to severe ACS were retrospectively reviewed by two observers, who listed the number of bronchopulmonary segments showing consolidation; areas of ground-glass attenuation due to early hemorrhagic edema; and paucity or absence of small vessels, arterioles, and venules. In all patients, the degree of hypoxia was out of proportion to the extent of consolidation evident at chest radiography. The CT scans showed microvascular occlusion and areas of ground-glass attenuation in nine patients. Infection was ruled out in eight patients. High-resolution CT may play an important role in the initial evaluation and timely selection of an appropriate treatment regimen aimed at improving tissue perfusion, thus forestalling irreversible organ damage and chronic pulmonary arterial hypertension in patients with sickle cell disease. PMID- 8451436 TI - Pulmonary embolism: increased ventilation in areas of decreased perfusion. AB - An abnormal finding that is considered characteristic of large or extensive pulmonary embolism has been observed on ventilation-perfusion (V-P) lung scans. This observation is a regional area of increased ventilation radioactivity in the embolized region of the lung that is more than the normal ventilation radioactivity in the adjacent or contralateral normally perfused lung. It has been designated the "enhanced V-P mismatch sign." This sign was noted in 15 cases among approximately 700 routine V-P lung scans interpreted by a nuclear radiologist. Of these, large or extensive emboli were confirmed in only 10 cases, nine by means of angiography and one by means of autopsy studies. The remaining five cases demonstrated clinical correlation only and are not included in this report. Of the 10 confirmed cases with enhanced V-P mismatch sign, increased ventilation radioactivity involved unilateral lung distribution in five and zonal or lobar distribution in five. The Westermark sign was seen in only seven of the 10 cases. It is hoped that this observation will prove useful in the diagnosis of large or extensive pulmonary emboli. PMID- 8451437 TI - Variable compensation chest radiography performed with a computed radiography system: design considerations and initial clinical experience. AB - The authors describe a variable compensation (VC) technique in which an x-ray equalizer and a computed radiography system are used. The VC technique allows retrospective alteration of equalized chest appearance with maintenance of improved signal-to-noise ratio in dense regions. Two imaging plates are used: one upstream of the patient to record the incident beam profile and one down-stream to record the equalized image. Subtraction of a weighted version of the upstream image from the down-stream image permits alteration of the appearance of the VC image, from the extremes of stimulated-unequalized to highly equalized. VC image appearance was optimized with a real-time workstation. The quality of VC images obtained in 33 patients was evaluated by three chest radiologists. Mediastinal appearance was better on VC equalized images than on conventional screen-film images. The stimulation of the appearance of a conventional radiograph with VC proved useful in interpretation of lung appearances on equalized radiographs. PMID- 8451438 TI - Alveolar consolidation detection: advanced multiple beam equalization radiography versus conventional chest radiography. AB - Advanced multiple beam equalization radiography (AMBER) and conventional chest radiography were prospectively evaluated in the detection and quantitation of alveolar (air-space) consolidation. Thirty-seven healthy volunteers underwent bronchoalveolar lavage (BAL), the retained lavage fluid serving as a model for alveolar consolidation. After BAL, the subjects underwent AMBER and conventional chest radiography. The lower lung zones on the radiographs were divided into four zones and graded for alveolar consolidation by three observers. There was no significant difference in the area under the receiver operating characteristic curve between the two techniques in the detection of lavage fluid. The grade of opacification was rated significantly higher (P < .05) on conventional radiographs for three of the four lung zones examined, and the correlation between the quantity of retained lavage fluid and grade of opacity was better on conventional radiographs. Detection of lavage fluid was poor with either technique. The exposure compensation of AMBER was evident in this model of air space disease but did not affect overall observer performance. PMID- 8451439 TI - A survey of interventional mammography practices. AB - To evaluate the current state of interventional mammography in the United States, surveys were sent to 1,000 randomly selected active members of the American College of Radiology (group 1) and the entire 1991 membership (n = 73) of the Society of Breast Imaging (group 2). Three hundred seventy-one (37%) group 1 and 49 (67%) group 2 responses were received. Some respondents did not answer all questions. Of group 1 respondents, 331 (93%) performed preoperative needle localization and 272 (73%) used a hook wire; 92 (25%), a J wire; and 55 (15%), a needle-dye technique. For group 2 respondents and these techniques, the results were 45 (94%), 32 (65%), eight (16%), and seven (14%), respectively. One hundred ninety-nine (62%) group 1 and 24 (55%) group 2 physicians administered local anesthetic during needle localization. Fifty-six (16%) group 1 and 25 (56%) group 2 physicians performed fine-needle aspiration cytology, as opposed to 11 (3%) and nine (20%) for core-needle biopsy, respectively. Cyst aspiration was performed by 245 (70%) group 1 and 40 (82%) group 2 respondents, galactography by 126 (36%) of group 1 and 30 (61%) of group 2, and pneumocystography by 57 (16%) of group 1 and 23 (48%) of group 2. For most procedures, informed consent was obtained by a minority of radiologists in both groups. PMID- 8451440 TI - A private breast imaging practice: medical audit of 25,788 screening and 1,077 diagnostic examinations. AB - During 1989 and 1990, 25,788 screening and 1,077 diagnostic breast imaging examinations were performed. Audit was performed in 6-month intervals to allow comparison of performance over time. Sensitivity, positive predictive value, and stage of disease were determined for each radiologist, for patients over and those under 50 years of age, and for patients with and for those without a suspect palpable breast abnormality. In the screening portion of the study, 1,539 of 25,788 (5.9%) patients were asked to return for diagnostic breast imaging, 119 of 188 (63%) cancers were stage 0 or stage 1 disease, and a sensitivity of 91% and a positive predictive value of 11% were found. If patients with a palpable breast abnormality were eliminated, 103 of 138 (75%) patients had disease that was less than stage 2. In the diagnostic portion of the study, 296 of 1,077 (27%) patients were referred for biopsy and 53 of 71 (75%) cancers were stage 0 or stage 1 disease. A sensitivity of 97% and a positive predictive value of 24% were found. If patients with a palpable breast abnormality were eliminated, 51 of 63 (81%) patients had disease that was less than stage 2. PMID- 8451441 TI - Artificial neural networks in mammography: application to decision making in the diagnosis of breast cancer. AB - The authors investigated the potential utility of artificial neural networks as a decision-making aid to radiologists in the analysis of mammographic data. Three layer, feed-forward neural networks with a back-propagation algorithm were trained for the interpretation of mammograms on the basis of features extracted from mammograms by experienced radiologists. A network that used 43 image features performed well in distinguishing between benign and malignant lesions, yielding a value of 0.95 for the area under the receiver operating characteristic curve for textbook cases in a test with the round-robin method. With clinical cases, the performance of a neural network in merging 14 radiologist-extracted features of lesions to distinguish between benign and malignant lesions was found to be higher than the average performance of attending and resident radiologists alone (without the aid of a neural network). The authors conclude that such networks may provide a potentially useful tool in the mammographic decision making task of distinguishing between benign and malignant lesions. PMID- 8451442 TI - Selective MR imaging of silicone with the three-point Dixon technique. AB - Selective magnetic resonance (MR) imaging of silicone with the three-point Dixon technique was evaluated. This technique, which conventionally allows separation of lipid and water signals, was modified to allow calculation of a silicone-only image and a lipid-water image. Imaging of fat and silicone implant phantoms was performed with a 1.5-T imager and was optimized in vivo in two volunteers who had breast reconstruction or augmentation. Six additional volunteers were then imaged to evaluate selective MR imaging of silicone. With an optimum frequency shift of 105 Hz, a repetition time of 1,000 msec, and an echo time of 28 msec, the modified three-point Dixon technique produced a silicone-only image containing 97.0% +/- 1.0 (standard deviation) of the total silicone signal, 2.6% +/- 0.5 of the fat signal, and 16.6% +/- 6.4 of the water signal. The silicone-fat contrast to-noise ratio was 47.9 +/- 12.1. This method may be potentially useful in the evaluation of implant-related complications such as rupture. PMID- 8451443 TI - CT- and US-guided biopsy of the pancreas. AB - A retrospective review of 211 computed tomographic (CT)-guided and 58 ultrasound (US)-guided biopsies of pancreatic lesions performed between 1985 and 1989 was undertaken to evaluate the accuracy of diagnosis and the number of complications. Combined CT and US accuracy in the diagnosis of malignancy was 93%. CT-guided biopsies had an accuracy of 86%, and US-guided biopsies had an accuracy of 95%. Accuracy was higher with larger masses (> 3.0 cm, 92%; < or = 3 cm, 81%) and larger needle sizes (16-19 gauge, 92%; 20-22 gauge, 85%) and when the mass was located in the body or tail of the pancreas (93%) rather than the head (84%). Major complications developed in three cases (1.1%). No biopsy-related deaths occurred. Needle passage through the gastrointestinal tract, including the colon, did not cause complications. PMID- 8451444 TI - [Folding and stability of protein molecule: from peptides to oligomeric proteins as a model]. PMID- 8451445 TI - [Autophagy in yeast]. PMID- 8451446 TI - [Evolution of the nuclease-type colicins and their immunity specificities]. PMID- 8451448 TI - [Accelerated mapping of the human genome]. PMID- 8451447 TI - [Molecular mechanism of trans-kingdom conjugation between Escherichia coli and yeasts]. PMID- 8451449 TI - [Apoptosis; its significance in cancer]. PMID- 8451450 TI - [Apoptosis in Lymphocytes]. PMID- 8451451 TI - [Induction of apoptosis by expression of the myc family gene]. PMID- 8451452 TI - [Tumorigenesis involving bcl-2 gene]. PMID- 8451453 TI - [Apoptosis, adhesion and growth factor of malignant T lymphoma cells]. PMID- 8451455 TI - [Gene recombination for human cancer therapy]. PMID- 8451454 TI - [Histologic features of neuroblastoma detected by mass screening]. PMID- 8451457 TI - [Comments on safe operation of ultracentrifuge]. PMID- 8451456 TI - [DNA-activated protein kinase]. PMID- 8451458 TI - Note and comment on "General deterrence of drunk driving: evaluation of recent American policies". PMID- 8451459 TI - A physiologically based pharmacokinetic assessment of tetrachloroethylene in groundwater for a bathing and showering determination. AB - A two-step methodology is described to make a health-based determination for the bathing and showering use of the water from a private well contaminated with volatile organic chemicals. The chemical perchloroethylene (PERC) is utilized to illustrate the approach. First, a chemical-specific exposure model is used to predict the concentration of PERC in the shower air, shower water, and in the air above the bathtub. Second, a physiologically based pharmacokinetic (PBPK) model is used to predict the concentration of PERC delivered to the target tissue, the brain, since the focus is on neurological endpoints. The simulation exercise includes concurrent dermal and inhalation routes of exposure. A reference target tissue level (RTTL) in the brain is estimated using the PBPK model. A hazard index based on this benchmark guideline is used to make a regulatory determination for bathing and showering use of the contaminated water. PMID- 8451460 TI - A compartmental model for the prediction of breath concentration and absorbed dose of chloroform after exposure while showering. AB - In order to predict the exhaled breath concentration of chloroform in individuals exposed to chloroform while showering, an existing physiologically based pharmacokinetic (PB-PK) model was modified to include a multicompartment, PB-PK model for the skin and a completely mixed shower exposure model. The PB-PK model of the skin included the stratum corneum as the principal resistance to absorption and a viable epidermis which is in dynamic equilibrium with the skin microcirculation. This model was calibrated with measured exhaled breath concentrations of chloroform in individuals exposed while showering with and without dermal absorption. The calibration effort indicated that the expected value of skin-blood partitioning coefficient would be 1.2 when the degree of transfer of chloroform from shower water into shower air was 61%. The stratum corneum permeability coefficient for chloroform was estimated to be within the range of 0.16-0.36 cm/hr and the expected value was 0.2 cm/hr. The estimated ratio of the dermally and inhaled absorbed doses ranged between 0.6 and 2.2 and the expected value was 0.75. These results indicate that for the purposes of risk assessment for dermal exposure to chloroform, a simple steady-state model can be used to predict the degree of dermal absorption and that a reasonable value of skin permeability coefficient for chloroform used in this model would be 0.2 cm/hr. Further research should be conducted to compare the elimination of chloroform via exhaled breath when different exposure routes are being compared. The model results from this study suggest that multiple measurements of exhaled breath concentrations after exposure may be necessary when making comparisons of breath concentrations that involve different exposure routes. PMID- 8451461 TI - Estimation of potential health effects from acute exposure to hydrogen fluoride using a "benchmark dose" approach. AB - Communities across the United States are examining the manufacture, use, transport, and storage of hydrogen fluoride (HF) near residential areas as a consequence of a major release of HF in Texas in 1987. Reference exposure levels for routine and accidental HF emissions are calculated using existing animal and human data. The approach employs a log-probit extrapolation of concentration response data to the 95% lower confidence limit on the toxic concentration producing a "benchmark dose" of 1% response (TC01), called a practical threshold. Species-specific and chemical-specific adjustment factors are applied to develop exposure levels applicable to the general public. Using this method, the 1-hr reference exposure level to protect the public against any irritation from a routine emission (REL-1) is 0.7 ppm and the level to protect against severe irritation from a once-in-a-lifetime (REL-2) release is 2 ppm. This approach is compared to a modified "uncertainty factor" approach. PMID- 8451462 TI - Pharmacokinetic modeling of trichloroethylene and trichloroacetic acid in humans. AB - The development and application of appropriate physiologically based pharmacokinetic (PBPK) models of chemical contaminants will provide a rational basis for risk assessment extrapolation. Trichloroethylene (TCE) is a widespread contaminant found in soil, groundwater, and the atmosphere. Exposures to TCE and its metabolites have been found to be carcinogenic in rodents. In this study, a PBPK model for TCE and its major metabolite, trichloroacetic acid (TCA), is developed for humans. The model parameters, estimated from the relevant published literature on human exposures to TCE and its metabolites, are described. Key parameters describing the metabolism of TCE and the kinetics of TCA were estimated by optimization. The optimization was accomplished by simultaneously matching model predictions to observations of TCE concentrations in blood and exhaled breath, TCA plasma concentrations, and urinary TCA excretion from five published studies. The optimized human PBPK model provides an excellent description of TCE and TCA kinetics. The predictions were especially good for TCA plasma concentrations following repeated TCE inhalation, an exposure scenario similar to that occurring in the workplace. The human PBPK model can be used to estimate dose metrics resulting from TCE exposures and is therefore useful when considering the estimation of human health risks associated with such exposures. PMID- 8451463 TI - Evaluating the risk of liver cancer in humans exposed to trichloroethylene using physiological models. AB - Trichloroethylene (TCE) is a widespread environmental pollutant. TCE is classified as a rodent carcinogen by the U.S. Environmental Protection Agency (EPA). Using the rodent cancer bioassay findings and estimates of metabolized dose, the EPA has estimated lifetime exposure cancer risks for humans that ingest TCE in drinking water or inhale TCE. In this study, a physiologically based pharmacokinetic (PB-PK) model for mice was used to simulate selected gavage and inhalation bioassays with TCE. Plausible dose-metrics thought to be linked with the mechanism of action for TCE carcinogenesis were selected. These dose-metrics, adjusted to reflect an average amount per day for a lifetime, were metabolism of TCE (AMET, mg/kg/day) and systemic concentration of TCA (AUCTCA, mg/L/day). These dose-metrics were then used in a linearized multistage model to estimate AMET and AUCTCA values that correspond to liver cancer risks of 1 in 1 million in mice. A human PB-PK model for TCE was then used to predict TCE concentrations in drinking water and air that would provide AMET and AUCTCA values equal to the predicted mice AMET and AUCTCA values that correspond to liver cancer risks of 1 in 1 million. For the dose-metrics, AMET and AUCTCA, the TCE concentrations in air were 10.0 and 0.1 ppb TCE (continuous exposure), respectively, and in water, 7 and 4 micrograms TCE/L, respectively. PMID- 8451464 TI - Response: relative versus absolute risk modeling of aflatoxin. PMID- 8451465 TI - [The need for radiologic control of the therapeutic caudal approach in adults]. PMID- 8451466 TI - [History of rachianesthesia with strychnine and stovaine in Spain]. PMID- 8451467 TI - [Tonsillar hypertrophy as a cause of upper airway obstruction]. PMID- 8451468 TI - [Epidemiology, quality control and anesthesia]. PMID- 8451469 TI - [Anesthetic morbimortality in a general hospital]. AB - INTRODUCTION: Due to the lack of data in our medium and epidemiologic study was performed with the aims of knowing the numbers of morbimortality of anesthesia in a tertiary hospital as well as identify the risk factors of the same. METHODS: A general prospective study was carried out with a sample of 5,162 anesthesias administered in our hospital from October 1986 to October 1987. The questionnaires undertaken were completed by the anesthesiologists of the hospital staff. Age, sex, ASA, emergency, associated preoperative pathologies, premedication, length of operation, duration fo anesthesia, anesthesiologist experience, type of surgery, type of anesthesia, monitoring, type of complications and evolution of the same were the variables assessed. Severe cases were also evaluated by 3 anesthesiologists of the department, independent of those involved. The relative risk and the confidence interval of 95% were calculated as were the chi of Mantel-Haenszel tendency and a test of mean comparisons. RESULTS: The mortality partially linked to anesthesia found was 1:2,581. The numbers of morbidity were of 0.77% for severe complications and 14.1% for the slight complications. Upon analysis of severe complications 28.5% of the cases were found to be due to human error. The principal risk factors were age, emergency, bad preoperative physical state, lenght of operation, type of anesthesia and surgery. CONCLUSIONS: The situation in our center does not differ from that found by other authors and not only the numbers of morbimortality but also the factors of risk found in this study are similar to those published in recent studies. PMID- 8451470 TI - [Synergism of midazolam and propofol in the induction of anesthesia]. AB - INTRODUCTION: The purpose of this study was to determine the possible interaction of midazolam and propofol in the induction of anesthesia. METHODS: A double-blind study of 90 ASA I-II women undergoing elective general surgery and gynecology was performed. The patients were divided into three groups of 30 patients receiving midazolam, propofol and a combination of both as the anesthesia induction agent. As a test of anesthetic induction the response to the verbal order of opening their eyes was evaluated. The dose-response curves for each group were determined by a logistic regression procedure while isobolographic analysis compared the actions of both agents separately and together. RESULTS: The ED50 in the propofol group was 1.56 mg.kg-1 and that of the midazolam group was 0.24 mg.kg-1. In the midazolam-propofol group the ED50 of midazolam was reduced approximately a quarter (0.068 mg.kg-1) when associated to the half of the ED50 of propofol anteriorly obtained. Isobolographic analysis revealed that the conjunctive action of both drugs was synergic (p = 0.04). CONCLUSIONS: Propofol potentiates the action of midazolam in anesthetic induction. Although this synergism also reduces with the association of thiopental-midazolam, the mechanism of action is not demonstrated as the same. Thiopental increases the affinity of the benzodiazepines for the GABA complex receptors which has not been described for propofol. PMID- 8451471 TI - [Effects of midazolam on the delivery and consumption of myocardial oxygen in the postoperative period of children undergoing heart surgery]. AB - INTRODUCTION: The aim of this study was to evaluate the effect of midazolam on the variables which determine myocardial oxygen delivery and consumption relationship (endocardiac viability index) in children undergoing cardiac surgery under extracorporal circulation. METHODS: The study was carried out in 15 children to whom a doses of midazolam of 0.2 mg/kg was given in immediate postoperative period upon hemodynamic stabilization. The determinations were performed prior to administration of the drug, at 5, 15, and 30 minutes thereafter. The variables analyzed were mean systemic blood pressure, mean diastolic pressure in aorta, mean pressure in the left auriculum, diastolic systolic time relation, arterial blood O2 content and index of endocardiac viability. RESULTS: The following variables were modified with respect to the basal contributing to an improvement in the endocardiac viability index. Mean aortic diastolic pressure decreased 10.05% at 5 min and 6.17% at 15 min (p < 0.05, p < 0.005); mean systemic arterial pressure decreased 10.64% at 5 min and 6.9% at 15 min (p < 0.05, p < 0.005); the mean pressure in the left auriculum decreased 6.28% at 5 and 8.32% at 15 min (p < 0.05); the diastolic-systolic time relation increased 24.04% at 5 min (p < 0.05, p < 0.005). The index of delivery and consumption of endocardiac oxygen increased 23.4% at 5 min (p < 0.05). CONCLUSIONS: The intravenous administration of midazolam to children at doses of 0.2 mg/kg during the postoperative period of cardiac surgery produced an improvement in the delivery and consumption of oxygen to endocardium at 5 minutes of its administration. PMID- 8451472 TI - [Effect of the administration of intralipid on liquid filtration rate and pressure of the pulmonary artery in isolated lung of rabbits]. AB - INTRODUCTION: We study the effect on Intralipid on pulmonary circulation. METHODS: A 10% infusion of Intralipid was administered at a dose of 0.5/kg in 14 isolated rabbit lungs in which constant blood flow infusion was carried out principally in zone 3. The liquid filtration rate (LFR) and the mean pressure of the pulmonary artery were measured. RESULTS: A constant increase of mean pressure of the pulmonary artery was observed following the infusion (from 12.32 +/- 3.66 cm of H2O to 39.92 +/- 07.68 cmH2O (p < 0.01) which was associated to a significant increase in the rate of liquid filtration (from 0.018 +/- 0.01 g/min to 0.198 +/- 0.04 g/min; p < 0.01). CONCLUSIONS: The administration of Intralipid produces a statistically significant increase of mean pressure of the pulmonary artery and the rate of liquid filtration. This is probably caused by vasoconstriction due to metabolic changes produced by Intralipid on pulmonary circulation. PMID- 8451473 TI - [Structure and function of an outpatient surgery unit]. AB - In order for a surgical intervention to be performed in an outpatient regime three basic requisites must be met: adequate patient selection, appropriate type of surgery and adequate unit. These factors are important for the surgical procedure to be carried out with identical safety and success as that undertaken in an admitted patient. In out patient surgery, early psychomotor recovery and slight or lack of secondary effects are fundamental; thus, anesthetic technique is selected keeping these two points in mind as they determine the criteria for the release of the patients from hospital. PMID- 8451474 TI - [Electroencephalographic effects of subhypnotic doses of midazolam in healthy subjects and in brain disease patients]. AB - The aim of this study was to analyze the electroencephalographic alterations produced by minimum doses of midazolam and look for a theoretic base for these changes in the benzodiazepinic receptor. To do so, the possible abnormal responses provoked by midazolam on the EEG of patients with ischemic cerebral infarctions were studied. Sub-hypnotic infusions of midazolam (0.15 mg kg/min) were administered prior to anesthetic induction in three groups of patients: control group, patients with tumoral cerebral pathology group, and ischemic cerebral infarctions group. In addition to the known modifications obtained in the patients of the control group, those presenting bioelectric activity alterations due to tumoral pathology did not show modifications. In the group of patients with ischemic infarctions, the intravenous perfusion of midazolam induced moderate increase in the localized theta and delta frequency and a lower representation of the beta rhythm which was also of lower amplitude. Midazolam is capable of making slow rhythms on the EEG, following it administration at low doses, in ischemic zones of the brain. PMID- 8451475 TI - [Intracavitary electrocardiography. A useful method for checking the correct localization of central venous catheters]. AB - A placement technique for central venous catheters (CVC) using the intracavitary electrocardiography (ICECG) as well as three different connection systems of the CVC to the electrocardiographic monitor are described. The aim of the present study was to evaluate the correct placement of the CVC by this technique with posterior radiologic confirmation being carried out. The study was undertaken in 30 patients connecting a CVC to a negative electrode of the standard lead II and the positive to the left leg. The CVC was advanced and the changes in the morphology of the "P" wave as it passed along the superior vena cava (SVC) to the right auricle (RA) were observed. In 28 of the 30 patients (93.3%) a biphasic "P" wave (right auricle) was achieved with the CVC being thereafter withdrawn until the SVC (this location was radiologically confirmed posteriorly). In 2 patients (6.6%) a biphasic "P" wave was not obtained and an abnormal position of the CVC was radiologically demonstrated at surgery (one in the ipsilateral subclavian vein and the other had a ring within the right subclavian vein impeding progression). The mean time used in the performance of this technique was 220 +/- 40 s. It is concluded that intracavitary electrocardiography is a simple, easy to learn and perform technique which does not delay surgical procedure and it is a reliable method for placing the end of the CVC. PMID- 8451476 TI - [New opiates in anesthesiology-resuscitation]. PMID- 8451477 TI - [General anesthesia in a patient with Dejerine-Sottas disease]. PMID- 8451478 TI - [Another phase in the discovery and introduction of anesthesia in Spain. Picturesque anecdotes]. PMID- 8451479 TI - [Heart arrhythmias (II). Experimental models and clinical arrhythmiology. New advances in the concept of re-entry]. PMID- 8451480 TI - [Acute myocardial infarction in cocaine addicts]. AB - The cases of 4 young patients (3 males, 1 female) addicts to cocaine with acute myocardial infarction is reported. In the first case, in a 28 year-old woman was found a multisystemic disorder with anterolateral myocardial infarction, acute renal failure, rhabdomyolysis and death. In the necropsy examination no atherosclerotic coronary lesions were found. In other two cases, was carried out coronary angiography, who revealed in one case normal angiographically coronary arteries, and in the other case, a 80% coronary narrowing in the proximal segment of the infarct-related coronary artery. We reviewed the cocaine-induced heart disease, and the pathophysiology of the acute myocardial infarction related to cocaine use. PMID- 8451481 TI - [Aortico-left ventricular tunnel. Clinical and surgical considerations]. AB - We report the case of an infant operated on at 11 months, having been clinically, echocardiographically and hemodynamically diagnosed when 2 days at the age. In the Echo-Doppler study the visualisation of the tunnel and the presence of aortic regurgitation within it and in the left ventricular outflow tract confirmed the diagnosis. Surgical access to both orifices, aortic and left ventricular, through the tunnel (after incision in the same) allowed it to be closed with two Goretex patches from its external face. This technique has a double advantage: a) it avoids annular distortions or aortic valvular lesions, b) excluding the tunnel (partial resection of edges and subsequent continuous suture) any possibility of subpulmonary stenosis through compression is eradicated. PMID- 8451482 TI - [Acute non-lethal complete occlusion of the left main coronary artery]. AB - Myocardial infarction secondary to total obstruction of the left main coronary artery is an infrequent finding in clinical practice. Even though this disease usually results in high mortality rates, various cases have been described documenting survival after complete occlusion of the left main trunk. We present a patient who survived after a massive myocardial infarction due to total obstruction of the left main coronary artery. Orthotopic cardiac transplantation was subsequently performed with good results. PMID- 8451483 TI - [Transesophageal echocardiography diagnosis of perforation of the mitral valve secondary to infective endocarditis]. AB - We report on a patient with infective endocarditis and severe mitral regurgitation secondary to perforation in the base of the posterior mitral leaflet. Transthoracic echocardiography was inconclusive. Only transesophageal echocardiography could confirm the presence of vegetations, their characteristics and the existence of valvular perforation. We also review the literature on the contribution of transesophageal echocardiography to the diagnosis of infective endocarditis and its complications. PMID- 8451484 TI - [Palliative interatrial septostomy in severe pulmonary hypertension]. AB - Three patients with severe pulmonary hypertension underwent palliative atrial septostomy by dilating the interatrial septum with valvuloplasty catheter balloons. In two cases successful dilation improved cardiac index and symptoms of cardiac failure (13 and 11 months follow-up). One patient died immediately post septotomy due to severe hypoxemia. Severe pulmonary hypertension with low cardiac output and high right ventricular filling pressures has a very poor short-term prognosis. Atrial septostomy is a useful palliative procedure and can serve as a bridge to heart and/or lung transplantation. It is not free of risk and the resultant systemic hypoxemia can lead to dead; that is why we recommend progressive balloon diameters, stopping the procedure when improvement of cardiac index is achieved with the minimal systemic oxygen desaturation. PMID- 8451485 TI - [Conventional stress test in patients with dilated cardiomyopathy. Variables with prognostic value. Correlations with non-invasive and invasive tests]. AB - The variables of conventional stress testing were studied to determine their prognostic value and their correlations with other tests, in 34 patients with dilated cardiomyopathy divided into a first group of 20 in-patients admitted because of acute pulmonary edema (GI), and a second group of 14 stable out patients (GII), with a mean follow-up of 3 years. The GI-patients had data of more evolved disease as reflected by a lower fractional shortening (13.5 +/- 4.6 vs 17.8 +/- 3.9%; p < 0.05). The only variables with prognostic capacity were functional aerobic incapacity (FAI), and systolic arterial pressure reached on exercise (SAPE), this being applicable only to GI-patients (FAI: 19.6 +/- 17.34 vs 46 +/- 26.4% in alive vs patients who died respectively; p < 0.05) (SAPE: 155 +/- 23.21 vs 127.14 +/- 24.9 mmHg, respectively; p < 0.05). Also a good correlation between the cardiac rate reached on exercise and the cardiothoracic index on chest X-ray was found (p = 0.0001), again, for GI-patients only. The presence of ventricular arrhythmias (VA) on stress testing had a very good correlation with a Holter VA-score (p < 0.0001), this being applicable for both GI and GII patients. The correlations with haemodynamic variables obtained by, basal or post-dobutamine infusion, right catheterism were not good by and large, except between FAI and systemic resistances. It is conclude that: 1) Conventional stress testing provides variables of prognostic value in dilated cardiomyopathy patients but only in those with more evolved disease. These variables are the FAI and the SAPE. 2) The presence of VA during exercise predicts their presence in daily life, and in this case at an earlier phase of the disease. 3) There are not good correlations between the haemodynamic and stress testing variables except in the case of systemic resistances and FAI. PMID- 8451486 TI - [Usefulness of the stress test in the evaluation and treatment of severe left ventricular dysfunction]. PMID- 8451487 TI - [Influence of the permeability of the artery responsible for the infarction on the variability of heart rate and late potentials. Its importance in the risk stratification after myocardial infarction]. AB - The use of the heart rate variability for the study of the Autonomic nervous system has been well established. We analyzed late potentials and heart rate variability in 29 control patients and in 102 consecutive patients with a first myocardial infarction. The data obtained were analyzed with both, the medical treatment (thrombolysis and beta-blockers) and the patency of the infarct related vessel. Patients with an infarct had diminished vagal tone as compared with the control group. Those patients with occluded related arteries showed higher incidence of late potentials; interestingly patients with late potentials also had diminished vagal tone. Without looking at the patency of the infarct related artery, thrombolitic and betablocker therapy did not have any effect on vagal tone. All the variables were correlated with the patency of the infarct related artery. Those patients with patent arteries had a preservation of the vagal tone; this was independent of the treatment received and the presence of late potentials. We concluded that the patency of the infarct related artery determines the absence of late potentials and preservation of the vagal tone. This might be one of the mechanisms of how thrombolitic therapy decreases the incidence of cardiac death. PMID- 8451488 TI - [Pulsed Doppler of the hepatic veins: a new test in the assessment of aortic insufficiency]. AB - In order to determine the value of the analysis of the hepatic vein flow pattern in the gradation of aortic regurgitation, two-dimensional and Doppler studies were carried out in 13 healthy individuals (control group) and 36 patients with aortic regurgitation (study group), in a prospective fashion. By 2-D and Doppler Echocardiography, aortic regurgitation was graded as mild in 5 patients, moderate in 13 and severe in the remaining. In 25 patients of the study group, hemodynamic and angiographic studies were available. Moderate or severe pulmonary hypertension was detected in 11 patients. Peak and integral velocities of the systolic, diastolic and "A" waves were measured on pulsed Doppler hepatic veins flow tracings. Both peak and integral hepatic vein diastolic flow velocities in postexpiratory apnea were significant lower in patients with severe aortic regurgitation with respect to the remaining study group patients and control group patients. Sensitivity and specificity for the detection of severe aortic regurgitation were 100 and 67% respectively. An postexpiratory increase in the retrograde "A" wave was observed in 11 patients with severe and 6 with moderate aortic regurgitation. Sensitivity and specificity for the detection of severe aortic regurgitation were 58 and 67% respectively. In this study, characteristic pulsed Doppler hepatic vein flow patterns are defined for patients with aortic regurgitation. Sensitivity and specificity of the findings allows the identification of severe AR. This results could have diagnostic and therapeutic implications. PMID- 8451489 TI - [Orthotopic heart transplant. Study of early morbimortality (< or = 30 days). Experience at the Reina Sofia Hospital (Cordoba)]. AB - From may 1986 to december 1991, we have performed 90 heart transplantation in the Hospital "Reina Sofia" from Cordoba. In the present study we analyze the early morbidity and mortality in a retrospective study on complications and factors determining its incidence. Seventy patients were male (86%) and 13 female (14%). Age ranged from 12 and 65 years. The 31% of patients needed in pharmacological support before transplantation, 15 of them were operated in a emergency situation because of cardiogenic shock. The pulmonary resistances oscillated between 0.5 and 8.7 units/m2 (Wood) (mean 2.5 +/- 1.4 units/m2). The mean time of ischaemia was 136 +/- 38 minutes (range 5-255 min). Hospital mortality (< or = 30 days) was 8.8% (8/90). No predictive factors from donor and recipient were found. Three main influences on complications were analyzed: a) influence of myocardial temperature, b) role of hematic cardioplegia, and c) usefulness of Aprotinin. Eighteen patients (20%) developed severe bradyarrhythmia needing a pacemaker in the post-operative period. We found a significant relationship with myocardial temperature (4.3 +/- 2.1 vs 6.2 +/- 2.6; p < 0.05) and transport solution temperature (5.8 +/- 2.3 vs 7.3 +/- 1.9; p < 0.05). No significant influence was found on the time of ischaemia, previous heart disease, previous treatment with Amiodarona, clinical condition, etc.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8451490 TI - [Prevention of asthma caused by dust mites]. AB - The house-dust mites are responsible for the majority of allergic asthma. It is currently possible to measure the exposure to their allergens, and this allows for a better guide as to the indications for eviction measures; there is also a more objective appreciation of the efficacy of these measures. A decrease in the relative humidity of the interior of the house effectively hinders the proliferation of the mites. Vacuuming the room, notably the mattress, is not sufficient in the majority of cases to reduce the level of allergenicity of the mites to a tolerable level for the asthmatic patient. Thus, it is necessary to renew the bedding, or to hermetically seal the mattress in a plastic cover. Washing the bedding at a temperature above 55 degrees C will kill the mites. Amongst the chemicals available in the struggle to reduce the mite population, the acaricides lead to an elimination of 65-100% of the mites in a mite culture. Tannic acid, which is a protein de-naturing agent, can reduce the allergenicity of the house-dust. Certain control studies related to the effect of the acaricides demonstrate an improvement in objective and subjective parameters of both asthma and rhinitis due to mites. However, the efficacy of these acaricides, as well as measures to clean up the environment within the house, merit more precise evaluation on the symptomatology, the changes of expiratory flow rates, and finally of broncho-reactivity in patients. It is probable that several preventative measures need to be associated if one wishes to improve the efficacy of the struggle to control the house-dust mites. PMID- 8451491 TI - [Preventive effect of an immunomodulator, OM-85 BV, on acute exacerbations of chronic bronchitis in elderly patients. Preliminary results at six months in 291 patients]. AB - Three hundred fifty six patients aged 65 years or more (mean age 81.8 years) who were suffering from chronic bronchitis were included in a double-blind trial against placebo to assess the preventative effect of OM-85 BV against acute exacerbations of chronic bronchitis. OM-85 BV is an immunostimulant composed of lyophilised factions of 8 bacteria which are most frequently encountered during the course of respiratory tract infections. 291 patients completed the study. In the group treated by OM-85 BV, a significant increase in the number of patients with no episode of acute bronchitis was noted (96 versus 71, p = 0.006). There was a 38.8% reduction in the absolute numbers of episodes of acute bronchitis and a 33% reduction in the number of prescriptions for antibiotics, however there was no difference in the number of pneumonias and bronchopneumonias. These results show the protective effect of OM-85 BV against bronchial superinfections in a large population of elderly patients suffering from chronic bronchitis. PMID- 8451492 TI - [Smoking habits of French general practitioners. Results of a representative sample of 1,012 physicians]. AB - General practitioners are in a position to influence the behaviour of the general population, notably as regards their smoking habits. This study aims to estimate the smoking habits of general practitioners in France, taken from a representative sample of 1012 general practitioners. The overall percentage of medical smokers rose in 1987 to 37%. The smoking habits varied according to age; thus if one considers current medical non-smokers, the oldest group are often ex smokers, while the youngest are usually those who have never smoked. Compared to information obtained in 1980 from the medical population, one notes that there has been a fall in the level of doctors who smoke, whilst the proportion of doctors who have never smoked has risen considerably during the same period, particularly amongst young doctors. PMID- 8451493 TI - [Alveolar opacities and busulfan pneumonia]. AB - A case of toxic pneumonia due to busulfan is reported in a man aged 65 treated for three years with busulfan for chronic myeloid leukaemia. He was admitted to hospital for dyspnoea, cough, fever and presented with crepitations, dense alveolar opacities, and a restrictive ventilatory defect. Trans-bronchial biopsy showed a filling of the alveoli by fibroblastic tissue, as well as voluminous dystrophic pneumocytes. Four months later in spite of steroid therapy the clinical state and respiratory function were worse. The alveolar opacities have regressed but some diffuse interstitial opacities had appeared. This new case is a reminder that the appearance of alveolar opacities in a patient treated with busulfan should raise the possibility of a toxic pneumonitis to busulfan in the differential diagnosis. This observation also underlines the role of the initial endo-alveolar fibrosis in the ultimate development of interstitial fibrosis. PMID- 8451494 TI - [Pleural mesothelioma and renal adenocarcinoma simultaneously discovered in a subject exposed to asbestos]. AB - We report a case of pleural mesothelioma and renal adenocarcinoma, discovered simultaneously in a patient aged sixty, who had had occupational exposure to asbestos between the ages of fourteen and twenty-eight. The contribution of asbestos in the occurrence of these malignant tumours is discussed in relation to the information contained in the literature. PMID- 8451495 TI - [Excision by video-thoracoscopy of a mediastinal bronchogenic cyst. A case report]. AB - A 42 year-old man was referred to surgery because of a symptomatic posterior mediastinal mass. Ablation was successfully performed via a video-thoracoscopic procedure avoiding a thoracotomy. The post-operative diagnosis was a bronchogenic cyst, as was the pre-operative diagnosis. The technical details are discussed. PMID- 8451496 TI - [Primary pulmonary hemangiopericytoma in a child]. AB - The authors report a case of a child, aged fourteen, who had a primary malignant pulmonary haemangiopericytoma. The diagnosis could only be made following the histological study of the excised pneumonectomy specimen and after silver staining. There was a fatal outcome some six months after the operation, despite satisfactory surgery and complementary chemotherapy. The rarity of this type of tumour, notably in children, justifies the presentation of this case report. PMID- 8451497 TI - [Goodpasture's syndrome presenting as acute respiratory distress. Favorable evolution with corticosteroids, cyclophosphamide and plasmapheresis]. AB - The authors report a case of a seventeen year old woman who was admitted to hospital for an extremely acute respiratory distress syndrome, which was revealed to be an exclusively pulmonary form of Goodpasture's syndrome. The positivity of the IgG immunofluorescence on open lung biopsy contrasted with the absence of circulating antibasement membrane antibody (ELISA). The combination of plasmapheresis, steroid therapy and cyclophosphamide enabled a rapidly favourable outcome and the patient could be weaned of the support therapy. PMID- 8451498 TI - [Excision of mediastinal nodes using video-thoracoscopy]. AB - A man of seventy-one years with gross respiratory failure was suspected of having a cancer of the right upper lobe with metastases to the right pretracheal and intertracheobronchial nodes. A diagnostic mediastinoscopy did not achieve a diagnosis, and a right sub-bronchial node biopsy was performed, using videothoracoscopy and this revealed the presence of tuberculosis without any further delay. PMID- 8451499 TI - [Collapsed balloon sign due to an unusual cause]. PMID- 8451500 TI - [An unusual, middle mediastinal opacity. Value of standard radiography with high resolution]. PMID- 8451501 TI - [Building before destroying]. PMID- 8451502 TI - [Comparison of bronchodilator effects and site of action of fenoterol and ipratropium in chronic obstructive bronchitis]. AB - There is no lack of data in the literature reporting on the efficacy of different bronchodilators. However, the discussion concerning the superiority of one bronchodilator over another in patients with chronic bronchitis and airflow obstruction is, and remains, a controversial subject. This has been particularly so since the perfection of synthetic anticholinergics delivered by inhalation without any side-effects. The aim of the present work is to compare the bronchodilator effects of a sympathomimetic, fenoterol (Berotec), and of an anticholinergic, ipratropium bromide (Atrovent), compared to a placebo in twelve unselected chronic bronchitics who had airflow obstruction and were in a stable clinical state. The bronchodilator effect of the two drugs was judged at the same time by variations on forced expired volume (FEV1) which was taken as a reference value, and of the maximum mid-expiratory flow (MEF) measured by spirography and also the variations of pulmonary resistance (delta Rrs) measured by the forced oscillatory method. The comparison of these indices enables the site of action of these agents to be specified. The dose response curve and the duration of action over six hours was assessed for each of the three agents. These were administered in succession and at random over three days by inhalation using an inhalation chamber. All the patients who were included were capable of producing a bronchodilator response but two of them responded only to one agent. The change in the FEV1 was comparable with the two active products. The change in MEF (an index of peripheral airways) was significantly greater following ipratropium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8451503 TI - [1992 Meetings of the Societies of Pneumology of the French Languages. Abstracts]. PMID- 8451504 TI - Intrathecal baclofen infusion: an innovative approach for controlling spinal spasticity. AB - Severe and disabling spasticity frequently occurs in people with multiple sclerosis and spinal cord injury. Approximately 30% of these people are treated with oral antispasmodic medications that do not provide adequate relief from spasticity (Hattab, 1980). Clinical trials with spinal stimulation and ablative neurosurgical procedures have not been as uniformly successful for controlling spasticity as has intrathecal baclofen injection (Kasdon, 1986). Delivered by an implantable programmable drug pump, intrathecal baclofen injection has proven to be successful in treating individuals with intractable spasticity. Significant reduction in muscle tone and frequency of spasms have contributed to improved function with activities of daily living, bladder management, overall comfort, and quality of sleep (Penn et al., 1989; Parke, Penn, Savoy, & Corcos, 1989). This article introduces an innovative therapy for controlling spasticity and discusses the nurse's role in patient selection and management. PMID- 8451505 TI - Geriatric rehabilitation: nursing challenge of the '90s. AB - This article describes the stages, problems, nursing approaches, and challenges involved in geriatric rehabilitation practice. The article is based largely on patient experiences and outcomes observed at Capital Region Geriatric Rehabilitation Center (Cohoes, NY), a unique new model geriatric rehabilitation facility. The nursing rewards of working in the field and some common myths of aging are emphasized. PMID- 8451506 TI - Establishing an employee injury prevention program. AB - In the years between 1987 and 1989, REHAB reduced injuries from 3.5 to 1 per 50 employees. This program continues, and REHAB continues to refine it to reduce the rate even more. A strong management commitment to prevent injuries, increased staff awareness, and a program for gradual return to work all were instrumental in a significant reduction of injuries at REHAB. PMID- 8451507 TI - Inside room 92. PMID- 8451508 TI - Trauma patient outcomes: six-month follow-up. AB - One hundred forty-six trauma patients discharged from an acute care setting to home were followed during a 6-month period after discharge to determine functional problems they experienced and the time required to return to normal activity levels. At 1 week, 58% were unable to drive a care, 59% experienced difficulty with lifting, and 76% were unable to return to work. At 1 month, 27% continued to have trouble driving, 32% had trouble lifting, and 37% had not returned to work yet. Head injury patients and those with orthopedic injuries of the extremities or pelvis experienced problems returning to work. The head injury group also experienced vocational problems. By 6 months, 89% of the patients reported a return to normal activities. Findings suggest that a return to normal functioning level is a long-term process, and that certain injury types are at high risk for experiencing specific identifiable problems. PMID- 8451509 TI - Long-term psychosocial effects of spinal cord injury. AB - Spinal cord injury typically occurs in males during late adolescence or young adulthood. These individuals face the developmental challenges of adulthood with significant restrictions in mobility and position. The purposes of this study were to examine how spinal cord injured male experience these limitations and to identify how they fulfill adult developmental tasks/expectations. Interviews on this topic were conducted with a convenience sample of 5 spinal cord injured men between the ages of 30 and 45 who had been injured at least 10 years. The findings of this study indicated that the impairment of mobility and position that resulted from the spinal cord injury did have a significant impact upon the developmental tasks/expectations of adulthood. Mobility and position restrictions delayed and/or interfered with the establishment of close personal relationships and the development of a satisfying career. Information also was obtained about the process of coping with the paralysis of a spinal cord injury over time. PMID- 8451510 TI - Guillain-Barre syndrome: a case study. AB - This article presents a case study illustrating the usual course of Guillain Barre syndrome. Rehabilitation nursing problems, interventions, and the outcome of a patient with Guillain-Barre syndrome are described. PMID- 8451511 TI - The effect of prior experience in a rehabilitation setting on students' attitudes toward the disabled. AB - The attitudes and reactions of rehabilitation nurses and nursing students toward patients with disabilities are important to the patients' adjustment and care over time. The purpose of this research study was to examine the effect of prior work experience and clinical experience in a rehabilitation setting on students' attitudes toward the disabled. The study involved the administration of Yuker, Block, and Young's (1966) Attitudes Toward Disabled Persons Scale (ATDP). Nursing students (N = 225) appropriately completed the ATDP before and 1 month after attending an educational workshop on care of people with disabilities. Prior work experience with such people was found to have a significant impact on student attitudes. Subjects with prior work experience in a rehabilitation setting had significantly higher scores on the ATDP, indicating more positive attitudes toward people with disabilities, than did subjects without this experience. Students who had clinical experience in a rehabilitation setting had higher scores on the ATDP than students without it, but the difference was not statistically significant. PMID- 8451512 TI - Chronically ill patients' perceptions of nursing care. AB - Chronically ill patients' perceptions of nursing care are particularly significant because such patients are more likely than others to have repeated and extended contact with nurses. Knowledge of which nursing interactions are perceived positively by the chronically ill can help nurses provide care that is satisfying to the patient. This phenomenological study found the definitive factor in positively perceived care to be the development and maintenance of confidence. The informants believed they would be well cared for and that the nurses were reliable and trustworthy. The respect and interest shown by the nurses reassured the informants that they were capable of coping with the future to the best of their abilities. Most informants felt unprepared to judge the nurses' competence but described a caring, compassionate approach combined with gentle handling, self-assurance, and recognition of the patient's own knowledge as contributing to confidence. Management of pain, facilitation of independence, and keeping the patient informed also were valued. PMID- 8451513 TI - Population biology of Toxoplasma gondii. PMID- 8451514 TI - Experimental models of toxoplasmosis. PMID- 8451515 TI - The current status of the glycobiology of Toxoplasma gondii: glycosylphosphatidylinositols, N- and O-linked glycans. PMID- 8451516 TI - Macrophage interactions in toxoplasmosis. PMID- 8451517 TI - Excreted/secreted antigens of Toxoplasma gondii--their origin and role in the host-parasite interaction. PMID- 8451518 TI - Role of P30 in host immunity and pathogenesis of T. gondii infection. PMID- 8451519 TI - Human T-cell clones as tools for the characterization of the cell-mediated immune response to Toxoplasma gondii. PMID- 8451520 TI - Mucosal immune response in toxoplasmosis. PMID- 8451521 TI - Immunogenetics influence outcome of Toxoplasma gondii infection. PMID- 8451522 TI - Toxoplasmic encephalitis in AIDS patients and experimental models for study of the disease and its treatment. PMID- 8451523 TI - The immunobiology of toxoplasmosis. PMID- 8451524 TI - Historical introduction: the Institut Pasteur's contribution. PMID- 8451525 TI - Modeling social and psychological determinants of exercise behaviors via structural equation systems. AB - Recent advances in structural modeling techniques allow for the testing of complex models representing social and behavioral processes. However, most reported applications in sport and physical activity have been limited to simple models involving variables measured at a single point in time. Therefore, the purpose of this article is to demonstrate the use of both cross-sectional and longitudinal latent variable modeling techniques by examining the relationships among efficacy cognitions, social support, and the exercise behaviors of sedentary adults. Results revealed a good fit for the re-specified model, suggesting the existence of a lagged feedback mechanism in which exercise behaviors influenced residual change in social support. In turn, efficacy cognitions appeared to serve a mediational function in the synchronous relationship between social support and exercise behavior. Findings are discussed in terms of the utility of structural equation modeling techniques for understanding the complex social and cognitive processes involved in exercise behavior. PMID- 8451527 TI - Telling the story: narrative in newspaper accounts of a men's collegiate basketball tournament. AB - The concept of narrative or story is increasingly being used as s theoretical model for informing research dealing with a wide array of sociocultural phenomena, especially those concerned with communication. Narrative is prevalent in mass media accounts of many different kinds of events. The inherent serialized structure of sport is conducive to media coverage in narrative form. This article uses a narrative perspective to examine journalistic accounts of the 1982 Atlantic Coast Conference (ACC) men's basketball tournament. We found that the accounts contain three major components of narrative: theme, plot, and characters. Winning is the central theme, and it contributes to shaping the plot and characters. The plot is simple and straightforward and centers on the question, "Who will win?" The characters are relatively flat and lack robustness- players offer exceptional athletic skills to coaches who strategically blend their talents. A breakdown occurs between the goal of winning and the goal of entertaining spectators, and this highlights the short-term importance of winning and the longer term importance of performing to entertain spectators. The narrative supports capitalistic economic relations, stemming from the central theme of winning and its ties to competitive individualism, teamwork, and consumerism. PMID- 8451526 TI - The effects of static and ballistic stretching on delayed onset muscle soreness and creatine kinase. AB - The purpose of this study was to determine if static and ballistic stretching would induce significant amounts of delayed onset muscle soreness (DOMS) and increases in creatine kinase (CK). Twenty males were randomly assigned to a static (STATIC) or ballistic stretching (BALLISTIC) group. All performed three sets of 17 stretches during a 90-min period, the only group difference being that STATIC remained stationary during each 60-s stretch while BALLISTIC performed bouncing movements. Subjective ratings of DOMS (scale: 1-10) and serum CK levels were assessed before and every 24 hours post stretching, for 5 days. A repeated measures ANOVA revealed a significant main effect due to time (p < 0.05), with peak soreness occurring at 24 hours after (M = 2.8 +/- 1.6). Surprisingly, a group effect (p < .05) demonstrated that DOMS was significantly greater for STATIC than for BALLISTIC. At 24 hours there was a 62% (p < .05) increase in CK for combined groups. These findings indicate that similar bouts of static and ballistic stretching induce significant increases in DOMS and CK in subjects unaccustomed to such exercise. Furthermore, static stretching induced significantly more DOMS than did ballistic. PMID- 8451528 TI - Frequency of modeling effects on the acquisition and retention of a motor skill. PMID- 8451529 TI - Validity of field tests of upper body muscular strength. AB - The purpose of this study was to determine the validity of five field tests (FTs) of upper body muscular strength and endurance (UBMSE) in 9-10-year-old children. Ninety-four children (38 boys, 56 girls) performed five FTs of UBMSE: pull-ups, flexed arm hang, push-ups, Vermont modified pull-ups (VMPU), and New York modified pull-ups. They also performed three criterion tests (CTs) of strength and three CTs of muscular endurance using a supported weight, set-resistance device. Zero-order correlations between the sum of the standard scores on the three CTs of strength (SUM1RM) and the FTs were nonsignificant. However, when SUM1RM was expressed relative to body weight (SUM1RM.kg-1), significant (p < .01) correlation coefficients were obtained for each FT. Highest correlations with SUM1RM.kg-1 were observed for the VMPU, and this same test yielded the smallest percentage of zero scores. Principal components analysis of the CTs, normalized for body weight, and FTs yielded a factor on which both the FTs and CTs of strength loaded significantly. These data indicate that the five FTs, though invalid as measures of absolute strength and muscular endurance, manifest concurrent and construct validity as measures of weight-relative muscular strength. PMID- 8451530 TI - The development of self-administered physical activity surveys for 4th grade students. AB - This study evaluates the test-retest reliability and validity of self-report measures of physical activity that can be self-administered in classroom settings to 4th grade students. Four different self-report formats were tested on 66 students. To assess test-retest reliabilities, self-report measures were administered on two occasions, separated by a 3-day interval between Time 1 (Friday) and Time 2 (Monday). One-way model intraclass reliabilities ranged from .51 to .74. Three days of monitoring with the Caltrac accelerometer were used as the validity criterion. Only one of the three weekly recalls, the Weekly Activity Checklist, was supported by significant validity correlations at both Time 1 (r = .34, p < .01) and Time 2 (r = .26, p < .05). The 1-day recall, Yesterday Activity Checklist, correlated significantly (r = .33, p < .01) with the previous day's Caltrac monitor score. Although two of the physical activity recall formats were found to be superior to two others, these data highlight the limitations of children's self-reports. Two self-report formats were found to have modest levels of reliability and validity with 4th grade children when administered in a classroom setting. PMID- 8451531 TI - Age-related differences in timing control of repetitive movement: application of the Wing-Kristofferson model. AB - Age differences in timing control were investigated in persons between 6 and 75 years. Subjects performed a repetitive finger-tapping task, attempting to match a 550-ms interresponse interval (IRI). Response variability was analyzed using the method of Wing-Kristofferson (1973). An autocovariance technique estimated the proportion of the overall (total) IRI variability contributed by central (clock) and peripheral implementation (motor delay) processes. Significant age and gender differences were revealed only for total and clock variability. Results indicated that (a) young children (6-7 years) had higher variances than all other age groups, (b) older children (9-10 years) were more variable than young and middle age adults, (c) variances did not differ significantly across three adult age groups (21-75 years), and (d) males were less variable than females for all age groups. In agreement with recent investigations that have used the Wing Kristofferson methodology, this study suggests that age-related differences in timing control are largely a function of central processes. PMID- 8451532 TI - A field test of the activity-set hypothesis for warm-up decrement in an open skill. AB - To determine the relative effectiveness of different warm-up activities in eliminating postrest warm-up decrement (WUD), 65 highly skilled tennis players performed 60 forehand and 60 backhand groundstrokes, rested for either 5 or 15 min, engaged in one of five interpolated activities (additional rest, running in place, imagery, practice swings, or air dribbling), and then performed 12 additional forehands and backhands. An analysis of differences between prerest and postrest arousal measures (heart rate, positive cognitive arousal, and negative cognitive arousal) revealed that all of the interpolated activities except additional rest restored arousal to levels near those found at the end of prerest trials. Postrest WUD was also eliminated by practice swings and air dribbling and, to a slightly lesser extent, by running in place. We concluded that an effective warm-up for open skills such as the tennis groundstroke should include some form of overt physical activity that direct the attention of the performer to task-relevant cues. PMID- 8451533 TI - Preactive and interactive decision-making tendencies of less and more experienced preservice teachers. AB - The purpose of this study was to describe the planning and interactive thoughts and decisions of less and more experienced preservice teachers (PTs). Twelve PTs, 6 less and 6 more experienced, planned, taught, and reviewed two lessons in lacrosse. While planning, the PTs were instructed to think aloud and verbalize their thoughts. After teaching, the PTs viewed six segments of their videotaped lessons and, following each segment, were presented with a set of questions, given orally. The verbal reports from the think aloud and stimulated recall sessions were audiotaped and transcribed. Descriptive analysis revealed that more experienced PTs made more information requests and decisions while planning than did less experienced PTs. During instruction, all subjects tended to teach from their plan when lessons were perceived to be progressing as planned. When lessons were perceived as not progressing as planned, the more experienced PTs tended to make lesson adjustments whereas the less experienced PTs tended to continue to teach without making any adjustment. These findings are discussed within the context of knowledge representation with implications for professional preparation. PMID- 8451534 TI - The development of curricular knowledge: a case of problematic pedagogical content knowledge during advanced knowledge acquisition. AB - The study examined what and how 12 K-8 physical education teacher education (PETE) majors learned about a movement approach that was discrepant from their experiences with physical education. This article describes one portion of the findings: what and how PETE majors learned about a movement approach to game play/strategy and mechanisms of advanced knowledge acquisition that contributed to confusion about this topic. Analytic induction and constant comparison were used to analyze qualitative data from interviews, observations, and relevant documents. Eleven PETE majors initially maintained partial or inaccurate conceptions about a movement approach to game play/strategy or taught this content in ways that were inconsistent with their goals for physical education, their knowledge about learning and teaching game skills, and the information presented by faculty and cooperating teachers. Interacting with students' prior knowledge and what and how faculty taught, the following learning mechanisms contributed to confusion: (a) overgeneralizing a contrast between a movement and traditional approach, (b) forming associations prior to adequate differentiation, and (c) overrelying on bottom-up thinking when initially developing lesson/unit progressions. PMID- 8451535 TI - Running-induced alterations in growth hormone, prolactin, triiodothyronine, and thyroxine concentrations in trained and untrained men and women. AB - This study examined whether gender and/or training were related to the exercise induced changes in plasma concentrations of growth hormone (GH), prolactin (PRL), triiodothyronine (T3), and thyroxine (T4). Twenty subjects (male and female 10-km runners; untrained males and females) ran on a treadmill for 30 min at 80% of previously determined maximum heart rate. Blood samples were taken through an indwelling catheter from an antecubital vein at -30, 0, +15, +30 min of the test and 30 min of recovery. Rectal temperature rose significantly (p < .01) at +15 and +30 min with concomitant rise in GH concentration, but PRL, T3, and T4 were not affected by the exercise. We concluded that a 30-min run at 80% of maximum heart rate is associated with higher concentrations of GH but not of PRL, T3, and T4. Neither training state nor gender affected the aforementioned results. PMID- 8451536 TI - Validation of a 20-minute steady-state jog as an estimate of peak oxygen uptake in adolescents. AB - Distance run tests are often used to estimate peak oxygen uptake (peak VO2) in children. This study examined the concurrent validity of a 20-min steady-state jog (20MSSJ). The sample consisted of 43 boys and 32 girls who performed a 20MSSJ and completed a maximal treadmill test 1 week later. Peak VO2 was measured by indirect calorimetry. Subject characteristics were as follows: boys, mean age = 15.1 +/- 1.0 years, mean peak VO2 = 46.4 +/- 7.7 ml.kg-1 x min-1, mean 20MSSJ = 2.3 +/- 0.5 miles; girls, mean age = 15.3 +/- 1.1 years, mean peak VO2 = 40.4 +/- 5.1 ml.kg-1 x min-1, mean 20MSSJ = 2.1 +/- 0.5 miles. The correlation between 20MSSJ and peak VO2 was .68 across boys and girls. The regression slopes of the boys and girls were common, but the intercepts differed, F (1, 72) = 10.9, p < .05. The influence of weight and skinfold fat was examined. Separate models were developed, and the R for each was increased to .79 (SEE = 4.45 ml.kg-1 x min-1) for the model using weight and .80 (SEE = 4.36 ml.kg-1 x min-1) for the model using sum of skinfolds. The regression equations are as follows: peak VO2 = 35.10 + 6.19 (Run) + 2.96 (Gender) -0.26 (Skinfold fat) peak VO2 = 33.94 + 7.64 (Run) + 5.84 (Gender) -0.18 (Weight) (Run = 20MSSJ performance in miles; Gender; females = 0, males = 1; Skinfold fat = sum of two-site skinfolds in mm; Weight = body weight in kg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8451537 TI - Coping strategies used by U.S. Olympic wrestlers. AB - Extensive in-depth interviews were conducted with all 20 members of the 1988 U.S. Olympic Wrestling Team regarding their efforts to cope with stress experienced during the Seoul Olympics. Qualitative analyses revealed that the wrestlers employed a variety of coping strategies including: (a) thought control strategies (blocking distractions, perspective taking, positive thinking, coping thoughts, and prayer), (b) task focus strategies (narrow, more immediate focus, concentrating on goals), (c) behavioral based strategies (changing or controlling the environment, following a set routine), and (d) emotional control strategies (arousal control, visualization). In accordance with the observations of Compas (1987) and Folkman and Lazarus (1985), the coping efforts of the Olympic wrestlers were not limited to particular strategies nor to single approaches to dealing with a particular stressor but, rather, reflected a dynamic complex process involving a number of strategies, often in combination. The results also suggested that the degree to which coping strategies are well learned or automatized is related to their perceived effectiveness. PMID- 8451538 TI - An examination of personal/situational variables, stress appraisal, and burnout in collegiate teacher-coaches. AB - Following Smith's (1986) cognitive-affective model of stress and burnout in athletics, this investigation examined (a) the relationship of personal/situational variables (social support, gender, and years of experience) to stress appraisal and (b) the relationship of stress appraisal (perceived stress, coaching issues, and role conflict) to burnout. Male (n = 99) and female (n = 115) teacher-head basketball coaches from NCAA Division III and NAIA colleges completed established measures of burnout, perceived stress, teacher coach role conflict, and social support and a measure of coaching issues developed for this study. Multivariate analyses supported the hypothesized relationships. Specifically, greater satisfaction with social support, less experience, and gender (females higher) were related to stress appraisal, and all stress appraisal variables were positively related to burnout. Contrary to previous studies, these teacher-coaches reported moderate to high levels of burnout. PMID- 8451539 TI - A nickel-binding serpin, pNiXa, induces maturation of Xenopus oocytes and shows synergism with oncogenic ras-p21 protein. AB - A nickel-binding serine proteinase inhibitor, pNiXa (43 kDa), was isolated from Xenopus ovary and assayed for effects on oocyte maturation. Microinjection of pNiXa (0.12 pmol/50 nl) induced maturation in 60% of Xenopus oocytes, beginning at 4 hours and reaching completion by 9 hours. Microinjection of oncogenic ras p21 protein (0.12 pmol/50 nl) induced maturation in 79% of oocytes, beginning at 6 hours and reaching completion by 12 hours. Microinjection of pNiXa in combination with ras-p21 protein had a synergistic effect on maturation, which occurred in 92% of oocytes, beginning at 4 hours and reaching completion by 9 hours. Oocyte maturation did not occur in control oocytes, which received a microinjection of bovine serum albumin. In oocytes exposed to a combination of pNiXa (0.12 pmol/50 nl, by microinjection) and progesterone (10 micrograms/ml, in the medium), maturation was intermediate (68% at 9 hours) between that induced by pNiXa (60%) or progesterone (85%) alone. This study shows (a) that pNiXa is a potent inducer of oocyte maturation, (b) that pNiXa's effect is synergistic with that of oncogenic ras-p21 protein, and (c) that pNiXa partially antagonizes progesterone induction of oocyte maturation. PMID- 8451540 TI - Effects of hypercholesterolemia on tissue antioxidant status in two species differing in susceptibility to atherosclerosis. AB - Uncontrolled oxidation has been implicated in the pathogenesis of atherosclerosis. In order to investigate the possible influence of hyperlipidemia on endogenous antioxidant status, the effects of dietary cholesterol supplementation on antioxidant enzymes and in vitro susceptibility to oxidative challenge (as measured by glutathione depletion and lipid peroxidation) were compared in two species exhibiting high and low susceptibilities to atherosclerosis, namely Japanese quail and rat, respectively. Standard diets were supplemented with cholesterol and cholic acid (1.0 and 0.5%, by weight, respectively) and assessments of antioxidant status made in red cells, liver, kidney and heart after 1, 2, 5 and 8 weeks. In contrast to the absence of detectable antioxidant alterations in rats, quail showed complex tissue-dependent changes, including increases (possibly adaptive) in antioxidant enzyme activities (usually first apparent at 2 weeks), enhanced susceptibility to peroxide-induced glutathione depletion (heart, kidney and liver) at 5 weeks and decreased sensitivity to lipid oxidation (heart and liver) at 8 weeks. Our results indicate an association of hyperlipidemia with complex time-dependent alterations in antioxidant components in an atherosclerosis-susceptible species prior to the appearance of visible atherosclerotic lesions. Future studies will focus on alterations in antioxidant components associated with atherosclerotic plaque development. PMID- 8451541 TI - Competitive irreversible inhibition of dopamine uptake by 6-hydroxydopamine. AB - We examined the effects of 6-hydroxydopamine (6-OHDA) treatment on the human neuroblastoma cell line SK-N-SH-SY5Y (SY5Y) and the rat pheochromocytoma cell line, PC12. Structural and metabolic integrity was tested by measuring the ability of cells to transport the non-metabolizable amino acid analogue [3H] alpha-aminoisobutyric acid (AIB). We determined that treatment with 6-OHDA at concentrations of 49 microM and 62 microM inhibited 50% of the AIB uptake in SY5Y and PC12 cells, respectively. Inhibition of AIB uptake was prevented by the addition of catalase, but was not influenced by the addition of 1 mM dopamine. This indicated that cell damage resulted from the generation of H2O2 and was independent of the catecholamine uptake system. Effects directly on the catecholamine uptake system were observed by measuring the uptake of 3H-dopamine. In contrast to the effects on amino acid uptake, dopamine uptake was significantly inhibited by 6-OHDA treatment, and this inhibition was not prevented by the addition of catalase. The results indicate a Ki of 430 microM for inhibition of dopamine uptake by 6-OHDA treatment of PC12 cells. The results are consistent with a competitive irreversible inhibition of the dopamine uptake sites by 6-OHDA or one of its metabolites. Thus, the lack of a catecholamine uptake-dependent cellular toxicity appears to result from the direct inactivation of catecholamine uptake sites. Similarly, the inhibition of dopamine uptake in vivo by 6-OHDA may be explained, at least in part, by direct inactivation of dopamine uptake sites rather than exclusively by intracellular transport and action of 6-OHDA. PMID- 8451542 TI - Effects of diabetes on the antinociceptive effects of intrathecally administered endothelin-1. AB - Intrathecal administration of endothelin-1 (ET-1) produced a dose-dependent increase in tail-pinch latency, i.e., antinociception, in both diabetic and non diabetic mice. The dose ranges which produced a significant antinociception in diabetic mice (0.0001 to 0.0003 nmol) were lower than those in non-diabetic mice (0.001 to 0.003 nmol). Furthermore, the antinociceptive effect of ET-1 in diabetic mice was decreased when the doses of ET-1 were increased. Indeed, when ET-1 in a dose of 0.003 nmol, which produced significant antinociception in non diabetic mice, it had no antinociceptive effect in diabetic mice. These results suggest that the mechanism which underlies the antinociceptive effects of ET-1 is up-regulated in diabetic mice, as compared with that in non-diabetic mice. PMID- 8451543 TI - Metformin and liver glycogen synthase activity in obese Zucker rats. AB - The effect of chronic treatment with metformin (320 mg/kg/day) on plasma glucose and insulin as well as liver glycogen synthase activity and hepatic glycogen content was studied in obese hyperinsulinemic Zucker rats. Metformin significantly reduced both plasma glucose (by 10%) and insulin levels (by 39%) at fasting but had no effect on hepatic glycogen content or on the basal activity of liver glycogen synthase. PMID- 8451544 TI - Leukocyte sensitivity to native human interstitial collagen in chronic liver disease. AB - Peripheral blood mononuclear cells and lymphocyte subsets separated from 28 patients with chronic liver diseases, and 11 age and sex matched normal controls were examined for cellular sensitivity to native human interstitial collagens and phytohemagglutinin, non-specific mitogen, by an in vitro leukocyte migration inhibitory test. The leukocyte sensitivity of peripheral blood mononuclear cells to type I, III, and V collagens was significantly higher in patients with chronic liver disease (26 +/- 10%, 25 +/- 11%, and 24 +/- 10%, respectively) than in controls (9 +/- 4%, 10 +/- 6%, and 9 +/- 3%, respectively, p < 0.001). Although the leukocyte sensitivity to phytohemagglutinin was significantly lower in patients with chronic liver disease than in controls (52 +/- 7% vs. 62 +/- 7%, p < 0.01). The leukocyte sensitivity to interstitial collagen in chronic liver disease was neither type specific nor disease specific, but it was correlated with the degree of hepatic fibrosis, or serum concentrations of procollagen type III peptide and 7S domain of type IV collagen. On the other hand, among subsets, the leukocyte sensitivity of T cells was significantly higher than that of B cells (p < 0.01), although there was no difference in leukocyte sensitivity between CD4 and CD8 T cells. These findings demonstrate that cellular immunity to interstitial collagen increases in chronic liver disease, reflecting the increased metabolism of hepatic collagen, in contrast to the pattern of decreased immunity to the non-specific mitogen. PMID- 8451545 TI - Nickel effects on hepatic amino acids. AB - Female Wistar rats were treated with nickel (single i.p. injection of 6 mg Ni(II)/kg body weight) and twenty amino acids and glutathione (GSH) concentrations were determined in liver 90 minutes later. Hepatic GSH content dramatically diminished after nickel injection. Glycine and glutamate levels, precursor amino acids of GSH, were not affected by nickel treatment, whereas cysteine level, the third precursor, was drastically increased in comparison with control rats. These findings showed that hepatic GSH depletion, caused by acute nickel exposure, was not due to a reduction in the availability of precursor amino acids. Nickel treatment also induced a 2-fold increase in phenylalanine and a decrease in taurine to one fifth. Therefore, the role of taurine in protecting membranes was clearly jeopardized in liver after nickel exposure, which could account for some of the toxicologic actions of this metal. However, further research is needed to explore such suggestion. PMID- 8451546 TI - Development of an in vitro hepatotoxicity assay for assessing the effects of chronic drug exposure. AB - We have used the human hepatoma cell line HepG2 to compare the hepatotoxic effects of acute (24 hr) and chronic (up to 10 days) exposure to amitriptyline, paracetamol and ondansetron. In acute exposure studies, hepatotoxicity was assessed by the sulforhodamine B protein staining method, where amitriptyline and paracetamol produced 50% hepatotoxicity at concentration of 30 microM and 7 mM, respectively, while ondansetron was non-hepatotoxic at 100 microM, the highest concentration used. In chronic exposure studies, the morphology of HepG2 cells was assessed by phase microscopy every 2 days and the compounds, at concentrations determined from the acute assay, were added fresh every 2 days. Chronic exposure to amitriptyline and paracetamol produced significant morphological changes in HepG2 cells at 3 microM and 1 mM respectively, concentrations which had no significant effect in the acute assay. Ondansetron (100 microM) produced only slight morphological changes in the cells after 10 days of culture. The combination of acute and chronic drug exposure assays with HepG2 cells represents novel in vitro systems for the hepatotoxicological assessment of drugs intended for human use. PMID- 8451547 TI - Anti-inflammatory treatment of muscular injuries in sports. PMID- 8451549 TI - Physiological aspects and injury in elite Alpine skiers. AB - Alpine skiing requires aerobic and anaerobic power, muscular strength, and a variety of complex motor abilities including quickness, agility, balance and coordination. There is evidence of variability in physical characteristics between skiers of different events. Generally, successful alpine competitors are taller and heavier than in the past. Greater size, specifically lean mass, may be related to technique changes because of the advent of breakaway poles. Aerobic power, although important, does not discriminate competitors of varying ability categories. Aerobic power is more likely to be a result of conditioning for alpine skiing rather than a profound requirement of the sport. Anaerobic power is important for skiing and both laboratory and field power tests correlate well with performance. Tests that measure explosive and sustained anaerobic power such as the Wingate, vertical jump, 60-second repeated jump, and Margaria-Kalamen stair run are valuable in assessing skiers. On-snow lactate and oxygen consumption measurements further substantiate the need for high anaerobic power. Alpine skiers have very high leg strength compared with other athletes. Isokinetic testing has been used to evaluate dynamic leg strength in skiers, but little is known about high speed dynamic or eccentric strength capabilities. A new mechanism of knee injury that is associated with tibial acceleration has been identified in competitive alpine skiers. A release binding that is sensitive to physiological factors in addition to release forces should be developed. Strength profiling of skiers may also be valuable in evaluating injury risk. PMID- 8451548 TI - Exercise and male factor infertility. AB - Recent advances in the study of andrology are unfolding some of the idiopathic components of male factor infertility. The inclusion of exercise training as a component of male factor infertility has been proposed secondary to changes observed in the reproductive hormone and semen profile of some endurance trained male athletes. Evidence exists that a subset of endurance trained men, particularly runners, present with subclinical changes in their reproductive hormone profile. These changes include a reduction in total and free testosterone, alterations in luteinising hormone release and alterations in pituitary responses to gonadotrophin-releasing hormone and other pharmacological perturbations. Less attention has been directed towards identifying changes in spermatogenesis and fertility capacity as a result of endurance training. The semen ejaculate of some endurance trained athletes presents with nonspecific modifications including a low normal sperm count, decreased motility and several morphological changes that may compromise fertility. Thus, although a subset of high mileage endurance trained runners present with subclinical modifications in their reproductive hormone and semen profile, to date there is no evidence that endurance training causes male infertility. Future investigations should focus on the clinical impact these hormone and semen alterations may have on fertility capacity in endurance trained athletes. PMID- 8451551 TI - Biomechanical effects of functional knee bracing. Practical implications. AB - Bracing of the anterior cruciate-deficient knee remains controversial. Close review of published data has revealed enough common observations about braces that strong suggestive information can be utilised for clinical purposes until more concrete data are provided. Brace function can vary with design. The primary differences noted are between the shell-type and strap-type braces. Shell braces tend to provide more stability to the knee than do the strap braces. Proper hinge placement, rather than type, affects pistoning and overall performance of the brace. Custom braces provide a better fit than off-the-shelf devices, but they can feel more restrictive, especially the shell braces. Static bench-testing data have shown that these braces provide little stability against anterior tibial translation at forces comparable to athletic play. Yet kinematic and force plate data suggest that they may produce some mechanical constraining effect to the entire lower extremity instead of just the knee joint. The literature still supports the philosophy that functional bracing should be considered as part of a comprehensive rehabilitation programme for an anterior cruciate-deficient athlete with significant functional deficits. PMID- 8451552 TI - [Preanesthetic evaluation in obstetrics: loco-regional anesthesia and hemostatic disorders]. PMID- 8451550 TI - Aging, training and exercise. A review of effects on plasma glutathione and lipid peroxides. AB - Changes in plasma glutathione (reduced form: GSH; oxidised form: GSSG) and lipid peroxides (LPO) levels occur with aging, training and acute physical exercise. Sources of plasma GSH, GSSG and LPO include the liver and skeletal muscle. Aging appears to be accelerated because of a decrease in the antioxidant capacity of tissues reflected in a decreased plasma GSH level. This age-dependent change could be partly compensated by physical training. Skeletal muscle appears to be able to deliver GSH into circulation with the adaptation of muscle to exercise training reflected in an increased plasma GSH level in the trained subject. Decreased plasma GSH concentration following physical exercise demonstrates increased GSH consumption in skeletal muscle resulting in a reduced export rate from muscle into plasma. The GSH system is able to effectively protect tissues against lipid peroxidation initiated by oxygen-derived free radicals produced in the intermediate metabolism during exercise. It can be assumed that the rate of this free radical production is a function of oxygen flow through organ and muscle tissue. PMID- 8451553 TI - [Are complementary preoperative studies useful?]. PMID- 8451554 TI - [What to expect from complementary preoperative studies in asymptomatic subjects (ASA 1)]. PMID- 8451555 TI - [Current status of surgery for urinary calculi]. PMID- 8451556 TI - [Use of the holmium 2.1 laser in surgical arthroscopy]. AB - After having been used for several years in medicine, laser energy has now been applied to arthroscopic surgery. Laser Holmium 2.1 is presently one of the most advanced machine in this field. We present here our initial experience in 40 cases compared with a control group of 40 cases treated by traditional arthroscopic surgery. This approach is less traumatic, the operative time is reduced and the postoperative period is characterized by a more complete recovery of motility and a reduction in postoperative pain. PMID- 8451557 TI - [Diagnosis and treatment of colonic polyps]. PMID- 8451558 TI - [Metabolic adaptation during fasting]. PMID- 8451559 TI - [Alcohol and medicine]. PMID- 8451560 TI - [60 years of vaccination against diphtheria in Geneva. A few pages of history in the light of group immunity]. PMID- 8451561 TI - [Trauma pathology of the upper limbs in the general practitioner's office]. PMID- 8451562 TI - [Cesar Roux' esophago-jejuno-gastrostomosis]. PMID- 8451563 TI - [Prescription of preoperative paraclinical studies: Let's take score!]. PMID- 8451564 TI - [Preoperative studies: observations on the current situation in a university center]. PMID- 8451565 TI - [Evaluation of preoperative paraclinical studies, in France, since 1981]. PMID- 8451566 TI - [Informatics in nursing]. PMID- 8451568 TI - [Nursing performance in occupational health]. PMID- 8451567 TI - [The Denver Test. Its application in the nursing consultation]. PMID- 8451569 TI - [The hemoculture. Its importance in the hospital environment]. PMID- 8451570 TI - [Family violence. The intervention of health professionals]. PMID- 8451571 TI - [The methods of maternal education. A historical review]. PMID- 8451572 TI - [Infectious endocarditis]. PMID- 8451573 TI - [Obstructive apneas. Their treatment with CPAP]. PMID- 8451574 TI - [Elementary knowledge of urinary incontinence]. PMID- 8451575 TI - [Diet and mortality from coronary heart diseases in Spain]. PMID- 8451576 TI - [The rigid bronchoscope]. PMID- 8451577 TI - [Continuing education. 75. Medical-surgical. Ketoacidotic coma]. PMID- 8451578 TI - [Heading toward a European health policy]. PMID- 8451579 TI - Stop that shivering! PMID- 8451580 TI - Ethics in action. What would you do? An elderly woman's i.m. diuretic is increased from twice a week to once a day. PMID- 8451581 TI - We put i.v. therapy down on paper. PMID- 8451582 TI - Patient teaching: cardioversion. PMID- 8451583 TI - Drug interactions we all overlook. Start with the medicine cabinet. PMID- 8451584 TI - Analgesics and anti-inflammatories. PMID- 8451585 TI - HIV vs. a nurse's right to work. PMID- 8451586 TI - Does milk cause juvenile diabetes? PMID- 8451587 TI - Are female MI patients being ignored? PMID- 8451588 TI - Ethics in action. What would you do? A doctor admits a female patient with acute lower back pain and orders only normal saline injections. PMID- 8451589 TI - Burn care basics and beyond. PMID- 8451590 TI - When heparin causes clots. PMID- 8451592 TI - FDA approvals: '92 in review. PMID- 8451591 TI - A little light makes venipuncture easier. PMID- 8451593 TI - Drug testing is here to stay. PMID- 8451594 TI - New guardians of the heart. PMID- 8451595 TI - No more shortage? PMID- 8451596 TI - Even the right decision can feel wrong. PMID- 8451597 TI - Support families of infants who've died of SIDS. PMID- 8451598 TI - Effect of allopurinol on myocardial recovery during reperfusion. AB - A comparative study on isolated guinea pig hearts was carried out to determine the effect of allopurinol added to reperfusion solution on myocardial recovery after global ischaemia. After 20 min of normothermic ischaemia two groups of solutions (1-Krebs Solution 2-Krebs Solution + Allopurinol 1 mmol l-1) were used for reperfusion (10 animals in each group). Post-ischaemic myocardial functions (ventricular contractile force and heart work) and enzyme activities (CK-MB, LD) were compared with their preischemic values. Addition of allopurinol 1 mmol l-1 to reperfusion solution improved post-ischaemic myocardial functions and decreased myocardial injury. PMID- 8451599 TI - Effect of intravenous glucagon infusion on renal haemodynamics and renal tubular handling of sodium in healthy humans. AB - The effects of a 2-h intravenous infusion of glucagon 5 ng kg-1 min-1 or placebo on glomerular filtration rate (GFR), renal plasma flow (RPF), tubular sodium handling as judged by the lithium clearance method, and plasma concentrations of angiotensin II (AngII), aldosterone (Aldo), and atrial natriuretic factor (ANF) were investigated in two groups of healthy human volunteers, glucagon group (n = 10), and placebo group (n = 10). Glucagon infusion resulted in a maximal increase in plasma concentrations of glucagon of 400%. GFR increased 5.9% (range 1.3-12.4, p < 0.001) through the whole infusion period, whereas RPF only increased transiently during the first hour of infusion 6.5% (range 2.6-15.3, p < 0.05). Whereas filtered load of sodium increased significantly in response to glucagon infusion (p < 0.001), urinary sodium excretion was unchanged. Neither of these variables were affected by placebo. As judged from assessments of tubular sodium handling derived from the renal clearance of lithium, the increased filtered load of sodium resulted in an increase in the output of sodium from the proximal tubules of a similar magnitude, and an increase in absolute reabsorption of sodium in the distal tubules totally counterbalancing this increased input to the distal tubules. These alterations in tubular sodium handling did not involve Ang II, Aldo, or ANF. We conclude that an increase in plasma concentration of glucagon within the physiological range is capable of inducing a small and sustained increase in GFR, whereas RPF increases only transiently.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8451600 TI - Comparative study of atrial peptides ANF (1-98) and ANF (99-126) as diagnostic markers of atrial distension in patients with cardiac disease. AB - To evaluate the possible role of atrial natriuretic peptides ANF (1-98) and ANF (99-126) as diagnostic parameters of atrial distension, measurements of peptide levels were performed in 47 patients with chronic ischemic and/or left sided valvular heart disease. Plasma samples were drawn from the pulmonary artery (PA) and superior vena cava (SVC) during diagnostic right heart catheterization. Forty of the patients also underwent left heart haemodynamic measurements, and in 28 patients two dimensional echocardiography with determination of left atrial diameter was performed. Enhanced plasma concentrations of both peptides were observed with increasing severity of heart failure assessed by the NYHA classification. Mean plasma levels of both peptides were closely correlated to mean pulmonary artery pressure (ANF (1-98): n = 47, r = 0.69 (SVC)/r = 0.72 (PA), p < 0.0001; ANF (99-126): n = 46, r = 0.75 (SVC)/r = 0.68 (PA), p < 0.0001) and mean pulmonary capillary wedge pressure (ANF (1-98): n = 47, r = 0.69 (SVC)/r = 0.72 (PA), p < 0.0001; ANF (99-126): n = 46, r = 0.70 (SVC)/r = 0.64 (PA), p < 0.0001). Positive correlations were also obtained between peptide levels and mean right atrial pressure and left ventricular end-diastolic pressure. When patients with high right atrial pressures (n = 2) were excluded from analysis, a significant correlation was found between peptide levels and echocardiography assessed left atrial diameter. The present study demonstrates the close correlation between concentrations of both atrial peptides and cardiopulmonary haemodynamics in patients with chronic heart disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8451601 TI - Commutability of control materials in cholesterol measurement. AB - The 'commutability' is the property of a material to show inter-assay changes comparable to those of patients' sera. In order to assess the commutability, the cholesterol concentration was measured in 107 patients' sera and in 24 lyophilized control materials by a direct enzymatic method and by a reference class procedure. The distance from the regression line of patients' sera results, expressed in SD units (normalized residual), was calculated and used to assess the commutability of each material. Out of 24 materials tested one had a normalized residual outside the +/- 3 interval (-4.4), and was considered as non commutable. However, the distribution of the normalized residuals from the remaining 23 materials suggested a different behaviour in comparison with patients' sera, in the specific pair of methods. The relevance of this finding to the control of accuracy is discussed. PMID- 8451602 TI - Central venous oxygen saturation during hypovolaemic shock in humans. AB - We compared central venous oxygen saturation and central venous pressure (CVP) as indices of the effective blood volume during 50 degrees head-up tilt (anti Trendelenburg's position) induced hypovolaemic shock in eight healthy subjects. Head-up tilt increased thoracic electrical impedance from 31 (28-36) (median and range) to 34 (30-40) Ohm, mean arterial pressure (MAP) from 79 (70-88) to 86 (80 99) mmHg, heart rate (HR) from 67 (56-71) to 99 (78-119) beats min-1 (p < 0.01) and total peripheral resistance (TPR) from 20 (16-32) to 36 (15-52) mmHg min l-1 (p < 0.03). Cardiac output decreased from 4.3 (3.0-4.8) to 2.7 (1.8-4.8) l min-1 (p < 0.03). After 29 (9-56) min presyncopal symptoms appeared, together with a decrease in MAP to 63 (43-79) mmHg, HR to 68 (30-112) beats min-1 and TPR to 22 (13-33) mmHg min l-1 (p < 0.02). During tilting CVP decreased from 3 (1-6) to 1 ( 3-5) mmHg (p < 0.05) but thereafter remained stable. In contrast, central venous oxygen saturation showed a linear decrease with time from 0.75 (0.69-0.78) at rest to 0.60 (0.49-0.67) (p < 0.01) when presyncopal symptoms appeared. Central venous catheterization is a tool for measurement of central venous oxygen saturation in addition to recording of CVP. The results suggest that a reduced central blood volume is reflected more clearly in central venous oxygen saturation than in CVP. PMID- 8451603 TI - Improved electrophoretic method for the analysis of dystrophin in human muscle. AB - A new simplified electrophoretic and Western blotting technique for the study of dystrophin in muscle biopsy material is presented and compared with immune histochemistry. The method is based on separation of dystrophin in a linear SDS PAGE pore gradient of 4-8% acrylamide in ultra-thin, horizontal gels on plastic film support followed by horizontal electrotransfer for Western blotting. The advantages of this procedure are short separation and transfer times at high field strength, high resolution, short staining procedures and small requirements of chemicals. Samples from the same gel can be cut and examined with different antibodies. Final results are obtained in one day. Examination of patients with various types of muscular dystrophies verified the essential absence of dystrophin in DMD patients, and showed considerable dystrophin heterogeneity in patients with BMD. A girl with severe symptoms of dystrophy revealed unexpected dystrophin abnormalities. The results also indicated that SDS-PAGE with Western blotting and immune histochemistry are complementary, diagnostic, and research instruments, and that the reactivity of commercial antibodies may differ in these two techniques. PMID- 8451604 TI - Automated procedure for measuring TBARS for in vitro comparison of the effect of antioxidants on tissues. AB - In this study we have evaluated a newly developed simplified automated continuous flow technique for the analysis of thiobarbituric acid-reactive-substances (TBARS). The method has been compared with a manual method for measurements of the potency for inhibition of TBARS formation by antioxidants in isolated renal tissue subjected to hypoxia and reoxygenation. The results presented in this report show that this new automated method is reliable, fast, and inexpensive. PMID- 8451605 TI - Coproporphyrin isomers in acute-intermittent porphyria. PMID- 8451606 TI - Sampling biases in studies of gender and schizophrenia. AB - Gender differences in schizophrenia are of great interest to researchers, and some have recently concluded that female patients suffer from a more benign form of the illness. However, the research findings do not support this conclusion consistently, and some reports suggest greater impairment in female patients. In this article, we discuss the potential effects of sampling biases on the findings from studies that compare male and female patients. More specifically, we assume that females do manifest a less severe schizophrenic illness than males, and we propose that sex differences in severity thresholds for voluntary and involuntary treatment are contributing to inconsistencies in the research findings. Some other sources of sampling bias that may influence findings on gender differences are also discussed. PMID- 8451607 TI - Parallel distributed processing and the emergence of schizophrenic symptoms. AB - Computer simulations of parallel distributed processing (PDP) neural networks have increased our understanding of brain functioning. This article reviews how PDP concepts can contribute to our understanding of schizophrenic symptoms. Psychotic states induced by phencyclidine and the adult form of metachromatic leukodystrophy, as well as neurometabolic studies, suggest that schizophrenia reflects a breakdown in communication between cortical areas. A computer simulation of this type of brain pathology has suggested two neurocognitive consequences: some cortical circuits will become functionally autonomous, and a subset of these circuits will yield "parasitic foci" that slavishly reproduce the same cognitive output. Delusions of control, paranoid delusions of the idee fixe type, thought broadcasting, "voices," and certain deficit symptoms are postulated outcomes of parasitic foci located at different levels of language processing. A neurodevelopmental model of impaired corticocortical communication is described, and this model's implications for further study are outlined. PMID- 8451608 TI - The New York High-Risk Project: anhedonia, attentional deviance, and psychopathology. AB - In the New York High-Risk Project (NYHRP) we followed subjects at risk for schizophrenic or affective disorders and low-risk controls from childhood to adulthood, with the goal of identifying early predictors of later schizophrenia related psychopathology. In this article, we focus on two potential predictors: the Physical Anhedonia Scale administered in adolescence and the Attention Deviance Index obtained in childhood. Subjects of this report are 161 members of the NYHRP's first sample (sample A), who had scores on both attention and anhedonia and had followup clinical assessments in adulthood. We used a path analysis model and several separate regression analyses to examine the relationships of the parent diagnostic groups, attentional dysfunction, and anhedonia to each other and to each of three psychopathological outcomes: schizophrenia and schizophrenia-related psychoses, major affective disorder, and social isolation in nonpsychotic subjects. Subject groups did not differ in anhedonia scores but did differ in childhood attentional dysfunction, psychosis, and social isolation, all of which are more common in subjects at risk for schizophrenia. In these subjects at risk for schizophrenia, but not in the other two groups of subjects, childhood attentional dysfunction is related to anhedonia, social isolation, and possibly nonparanoid psychosis. Anhedonia is associated with social isolation and with psychosis in females. Several other gender effects are also noted. PMID- 8451609 TI - Neurodynamics and schizophrenia research: editors' introduction. AB - The term, "neurodynamics," refers to interactions of large numbers of neurons that, in the short term, transform input information derived from their environments into meaningful outputs and, in the long term, use this information to alter their own architectures. This general concept may be useful in framing and investigating research questions that could advance our understanding of the nature, course, and treatment of schizophrenia. The mechanism of action of neuroleptics, the anatomic localization of schizophrenia, the stability of associated brain disturbances over time, and the distinction of state versus trait variables are briefly discussed as examples of issues whose understanding may be enhanced by a neurodynamic perspective. PMID- 8451610 TI - First person account: the onset of paranoia. AB - The article that follows is part of the Schizophrenia Bulletin's ongoing First Person Accounts series. We hope that mental health professionals--the Bulletin's primary audience--will take this opportunity to learn about the issues and difficulties confronted by consumers of mental health care. In addition, we hope that these accounts will give patients and families a better sense of not being alone in confronting the problems that can be anticipated by persons with serious emotional difficulties. We welcome other contributions from patients, ex patients, or family members. Our major editorial requirement is that such contributions be clearly written and organized, and that a novel or unique aspect of schizophrenia be described, with special emphasis on points that will be important for professionals. Clinicians who see articulate patients, with experiences they believe should be shared, might encourage these patients to submit their articles to First Person Accounts, Division of Clinical and Treatment Research, NIMH, 5600 Fishers Lane, Rm. 18C-06, Rockville, MD 20857.- The Editors. PMID- 8451611 TI - Hippocampal dysgenesis in mutant mouse and schizophrenic man: is there a relationship? AB - A rapidly growing body of data points to structural alterations of the temporal lobe in a significant number of schizophrenic patients. At the histological level, these changes are most frequently seen in the hippocampus and entorhinal cortex, and a strong case can be made for attributing them to disturbed neuroembryogenesis. Archicortical components of the temporal lobe are now known to follow an unusually complex course of embryological development, and we suggest that the process may be especially vulnerable to interference. A number of autosomal mutant mice express anomalies of hippocampal development, some of which resemble caricatures of the more subtle alterations in schizophrenic patients. We have suggested that at least some schizophrenias may result from the impact of maternal exposure to influenza virus during the period of neuroblast migration into the hippocampal primordium in the presence of as yet unspecified patterns of genetically transmitted immuno-incompetence. Although this putative interaction of genetic and epigenetic factors in humans probably differs from the factors involved in the mutant mouse, study of the murine model may reveal those mechanisms of embryogenesis that are most likely to be disturbed in the temporal lobe of schizophrenic patients. PMID- 8451612 TI - 31P nuclear magnetic resonance spectroscopy: neurodevelopment and schizophrenia. AB - A number of studies have demonstrated alterations in the structure and function of the frontolimbic system in some schizophrenic patients. Recent in vivo phosphorus-31 nuclear magnetic resonance studies of the dorsal prefrontal cortex in neuroleptic-naive, first-episode schizophrenic patients and matched controls have shown evidence of alterations in membrane phospholipid and energy metabolism. The membrane alterations observed in the schizophrenic patients are compatible with either premature aging or altered timing and exaggeration of regressive events occurring during normal brain development. These molecular changes may precede onset of clinical symptoms and brain structural changes in schizophrenia and suggest fresh approaches to the pathogenesis and treatment of this illness. PMID- 8451613 TI - Neurodynamics of abnormalities in cerebral metabolism and structure in schizophrenia. AB - Much evidence points to the importance of intrauterine events in the etiology of schizophrenia and suggests a complex interplay between dysfunctional and intact neurons in the pathophysiology of the disorder. This article contrasts what is known of the topographies of metabolic and structural brain abnormalities in schizophrenia at differing stages of the illness. From these contrasts, a schema is elaborated by which subtle neurodevelopmental perturbation in early to middle gestation might give rise to functional and structural abnormalities that ultimately release the diagnostic symptoms of schizophrenia. An interaction between those mechanisms mediating the expression of psychosis and the initially subtle stages of normal aging is posited to act on the substrate of a brain that is already developmentally compromised. Such a process might masquerade as "progression" in the absence of any active disease directly attributable to the original etiological event. PMID- 8451614 TI - Subtype progression and pathophysiologic deterioration in early schizophrenia. AB - It is important to elaborate what we know about the symptomatic, syndromal, and functional course of schizophrenia in order to test models for this illness. The sample of schizophrenic patients from the Chestnut Lodge followup study was subtyped using classical (modified DSM-III-R) criteria and deficit/nondeficit (Schedule for the Deficit Syndrome) criteria. During the first 5 years of manifest illness, the subtype phenomenologies were moderately stable. Instability consisted of a drift toward disorganization (hebephrenia) and nonspecificity (undifferentiated) among the classical subtypes, and toward the deficit subtype within that categorization. Over the same time, positive symptoms were relatively stable, but negative symptoms became significantly worse. Such changes probably reflect "deterioration" because they were associated with poorer functional outcome an average of 15 years later. These data dovetail with other reports in the literature and suggest a hierarchy of symptomatic/syndromal progression in early manifest schizophrenia that may reflect active deterioration processes at work. We suggest that any theory of schizophrenic pathophysiology must account for these patterns of symptom course. PMID- 8451615 TI - [Spontaneous remission in chronic lymphatic leukemia]. AB - We describe three patients with chronic lymphocytic leukemia who had a complete spontaneous remission, and review the cases reported in the literature. The mechanism leading to spontaneous remission is unknown, but it is speculated that the loss of a leukemia inducing oncogene or the reappearance of a leukemia suppressor gene could be involved. The interesting observation that, in some reported patients, the remission followed a viral infection, raises the question whether a virus-induced defense mechanism plays a causal role. PMID- 8451616 TI - [Interventional arrhythmology]. AB - Interventional arrhythmology deals with the nonpharmacological management of patients with symptomatic arrhythmias. Percutaneous catheter ablation is used to cure patients with arrhythmias due to accessory pathways or AV-node reentrant tachycardia. In patients with drug-refractory sustained, hemodynamically significant ventricular tachyarrhythmias, implantable third generation defibrillators provide an effective therapeutic modality. Our article provides a brief overview of these new therapeutic modalities and summarizes our local experience. PMID- 8451617 TI - [Concerning: "Behavioral neurology as basis of neurorehabilitation" by J. Kesselring (Schweiz. med. Wschr. 19912; 122: 1197-1205)]. PMID- 8451618 TI - [Annual Joint meeting of the Swiss Society of Cardiology and the Swiss Society of Thoracic and Cardiovascular Surgery. Bale, 1-3 April 1993. Abstracts]. PMID- 8451619 TI - Trends in Scottish cigarette smoking by gender, age and occupational status, 1984 1991. AB - Data from the General Household Survey (GHS) for the period 1984-1988 and data from the RUHBC-CATI (Research Unit in Health and Behavioural Change - Computer Assisted Telephone Interview) survey for the period 1988 to 1991 are pooled to study changes in the cigarette smoking prevalence in Scotland. It is concluded that the Scottish smoking prevalence shows a slight downward trend for males and a slight upward trend for females. There is some evidence for an earlier decrease in smoking prevalence related to a lower smoking uptake among younger generations, however, the current pattern of smoking among the youngest age group shows an increase. The reported difference in smoking prevalence between those in manual and non-manual occupations seems to be increasing among females and decreasing among males. PMID- 8451620 TI - Prevalence of maternal HIV infection in Scotland based on unlinked anonymous testing of newborn babies. Update. AB - In January 1990, unlinked anonymous testing of Guthrie cards for HIV antibody commenced in Scotland. Ethics Committee approval allowed testing of 99.6% of Scottish births. Twenty-one mothers spontaneously refused to allow testing of their baby's blood. Samples were coded by district postcodes. For 1990 through 1991, eluates of 132,531 dried blood spots were initially tested for HIV-1 antibody with the Fujirebio technique. Of the 49 positive samples 38 were confirmed to be positive by enzyme-linked immunosorbent assay and western blot (seroprevalence 0.3 per 1000). Thirty-five of 38 samples came from large metropolitan areas in Scotland. Prevalences were 2.0 per 1000 for Edinburgh city, 0.7 per 1000 for Dundee and Aberdeen, 0.15 per 1000 for Glasgow and 0.05 per thousand for all other areas in Scotland. Recent spread of HIV infection to Aberdeen may have occurred. These figures do not support an overall increase of HIV infection in childbearing women in Scotland. PMID- 8451621 TI - Epidemiology of Haemophilus type b invasive disease in childhood in Glasgow. AB - The objective of this study was to investigate the epidemiology of invasive disease due to Haemophilus influenzae type b in childhood in Glasgow. A retrospective study has been made on the hospital records of 252 children aged 0 to 12 years admitted to Glasgow hospitals during 1981-1990. The annual incidence of invasive Haemophilus influenzae type b disease in Glasgow was estimated at 39 per 100,000 children less than five years of age per year. The figure for Haemophilus meningitis was 23.8 per 100,000 children less than five years of age per year. Ninety-five per cent of all cases occurred in children less than five years of age and 72.1% of meningitis cases occurred before two years of age. There was a mortality of 2.77%. Long-term neurological sequelae were found in 15.3% of the survivors. The annual incidence of Haemophilus influenzae type b disease is slightly higher in Glasgow than previously reported for the United Kingdom. The study provides baseline data to help assess efficacy of proposed early childhood vaccination. PMID- 8451623 TI - Riedel's thyroiditis complicated by hypoparathyroidism and hypothyroidism. AB - Riedel's thyroiditis is a rare condition in which the thyroid gland is replaced by fibrous tissue. The case reported is one of Riedel's thyroiditis complicated by hypoparathyroidism and hypothyroidism. There would appear to have been only five earlier reports in the literature of hypoparathyroidism complicating Riedel's thyroiditis. PMID- 8451622 TI - Experience of a laboratory service for drug screening in urine. AB - The use of a drug screening service has been investigated over a nine month period during which 1500 urine samples from 765 patients were analysed. Preliminary drug screening of urine samples was performed by EMIT immunoassays adapted for use on the Cobas Bio analyser; further identification and confirmation were carried out by Toxi-Lab thin-layer chromatography and capillary gas chromatography. A large number of positive results were obtained for benzodiazepines, cannabinoids, methadone and opiates (mainly dihydrocodeine). Only a limited number of urines gave positive results for amphetamine and related stimulants; cocaine metabolite was rarely detected in samples. The service proved to be of considerable value in the management of drug misusers, and for the identification of new substances taken by the local population. PMID- 8451624 TI - Coronary artery ectasia: is it associated with myocardial ischaemia and infarction? AB - Coronary artery ectasia is an uncommon finding during coronary angiography. There may be associated stenoses of the affected arteries. We report three cases, which illustrate that ectasia, in the absence of obstructive disease, can result in myocardial ischaemia and infarction. PMID- 8451625 TI - Scotland's health: the road to the ills? PMID- 8451626 TI - Arabic caesarean section. Islamic history and current practice. PMID- 8451627 TI - Providing for women following miscarriage. AB - It is apparent that an increased awareness amongst health care workers of the need for parents to grieve the loss of their baby, regardless of the gestation, is essential. It should also be noted that this time of coming to terms with the loss can be quite lengthy. This healing may be aided by support groups such as the Miscarriage Association, and also through pre-pregnancy counselling clinics. Support in the next pregnancy appears to improve the chance of a successful pregnancy outcome in women with a history of recurrent miscarriages. It is important that the current interest in bereavement counselling does not lead to every miscarriage being 'magnified into a catastrophe'. For some women the event will pass with little trauma. In seeking to improve the management of this distressing condition we must be careful to take into consideration the individual's requirements. In a recent publication by SANDS, guidelines for the management of patients who have experienced the loss of a baby are given. This book can be commended for all involved in the care of women at the time of pregnancy loss. PMID- 8451629 TI - Basic research (III): Priorities. PMID- 8451628 TI - Tropical medicine: a changing scenario. PMID- 8451630 TI - House weighs in on NIH AIDS research. PMID- 8451631 TI - Bernadine Healy bows out. PMID- 8451632 TI - Biomedical research. Animal regulations overturned. PMID- 8451633 TI - Space woes begin to take a toll at UCSF. PMID- 8451634 TI - Gene linked to Lou Gehrig's disease. PMID- 8451635 TI - Toxicology goes molecular. PMID- 8451636 TI - Ken Olden heals NIEHS's 'split brain'. PMID- 8451637 TI - Cells in stress: transcriptional activation of heat shock genes. PMID- 8451638 TI - Molecular matchmakers. AB - Molecular matchmakers are a class of proteins that use the energy released from the hydrolysis of adenosine triphosphate to cause a conformational change in one or both components of a DNA binding protein pair to promote formation of a metastable DNA-protein complex. After matchmaking the matchmaker dissociates from the complex, permitting the matched protein to engage in other protein-protein interactions to bring about the effector function. Matchmaking is most commonly used under circumstances that require targeted, high-avidity DNA binding without relying solely on sequence specificity. Molecular matchmaking is an extensively used mechanism in repair, replication, and transcription and most likely in recombination and transposition reactions, too. PMID- 8451639 TI - On the application of the minimal principle to solve unknown structures. AB - The Shake-and-Bake method of structure determination is a new direct methods phasing algorithm based on a minimum-variance, phase invariant residual, which is referred to as the minimal principle. Previously, the algorithm had been applied only to known structures. This algorithm has now been applied to two previously unknown structures that contain 105 and 110 non-hydrogen atoms, respectively. This report focuses on (i) algorithmic and parametric optimizations of Shake-and Bake and (ii) the determination of two previously unknown structures. Traditional tangent formula phasing techniques were unable to unravel these two new structures. PMID- 8451640 TI - Structure-based discovery of inhibitors of thymidylate synthase. AB - A molecular docking computer program (DOCK) was used to screen the Fine Chemical Directory, a database of commercially available compounds, for molecules that are complementary to thymidylate synthase (TS), a chemotherapeutic target. Besides retrieving the substrate and several known inhibitors, DOCK proposed putative inhibitors previously unknown to bind to the enzyme. Three of these compounds inhibited Lactobacillus casei TS at submillimolar concentrations. One of these inhibitors, sulisobenzone, crystallized with TS in two configurations that differed from the DOCK-favored geometry: a counterion was bound in the substrate site, which resulted in a 6 to 9 angstrom displacement of the inhibitor. The structure of the complexes suggested another binding region in the active site that could be exploited. This region was probed with molecules sterically similar to sulisobenzone, which led to the identification of a family of phenolphthalein analogs that inhibit TS in the 1 to 30 micromolar range. These inhibitors do not resemble the substrates of the enzyme. A crystal structure of phenolphthalein with TS shows that it binds in the target site in a configuration that resembles the one suggested by DOCK. PMID- 8451641 TI - TH1 and TH2 cell antigen receptors in experimental leishmaniasis. AB - The complexity and chronicity of parasitic infections have obscured the identification of biologically relevant antigens. Analysis of the T cell receptor repertoire used by mice infected with Leishmania major revealed the expansion of a restricted population of CD4+ cells. These cells expressed the V alpha 8-J alpha TA72, V beta 4 heterodimer in both progressive infection and protective immunity and across several major histocompatibility haplotypes. Thus, the same immunodominant parasite epitope drives the disparate outcomes of this infectious process, suggesting that candidate vaccine antigens selected by screening of immune individuals may be capable of exacerbating disease in genetically susceptible individuals. PMID- 8451642 TI - Inhibition of human colon cancer growth by antibody-directed human LAK cells in SCID mice. AB - Advanced human colon cancer does not respond to lymphokine-activated killer (LAK) cells. In order to direct cytotoxic cells to the tumor, human LAK cells linked with antibodies to a tumor cell surface antigen were tested with established hepatic metastases in severe combined immunodeficient (SCID) mice. These cells had increased uptake into the tumor and suppression of tumor growth as compared with LAK cells alone, thereby improving the survival of tumor-bearing mice. Thus, tumor growth can be inhibited by targeted LAK cells, and SCID mice can be used to test the antitumor properties of human effector cells. PMID- 8451643 TI - Optical time-of-flight and absorbance imaging of biologic media. AB - Imaging the interior of living bodies with light may assist in the diagnosis and treatment of a number of clinical problems, which include the early detection of tumors and hypoxic cerebral injury. An existing picosecond time-of-flight and absorbance (TOFA) optical system has been used to image a model biologic system and a rat. Model measurements confirmed TOFA principles in systems with a high degree of photon scattering; rat images, which were constructed from the variable time delays experienced by a fixed fraction of early-arriving transmitted photons, revealed identifiable internal structure. A combination of light-based quantitative measurement and TOFA localization may have applications in continuous, noninvasive monitoring for structural imaging and spatial chemometric analysis in humans. PMID- 8451644 TI - Requirement for a GTPase-activating protein in vesicle budding from the endoplasmic reticulum. AB - The binding and hydrolysis of guanosine triphosphate (GTP) by the small GTP binding protein Sar1p is required to form transport vesicles from the endoplasmic reticulum (ER) in Saccharomyces cerevisiae. Experiments revealed that an interaction between Sar1p and the Sec23p subunit of an oligomeric protein is also required for vesicle budding. The isolated Sec23p subunit and the oligomeric complex stimulated guanosine triphosphatase (GTPase) activity of Sar1p 10- to 15 fold but did not activate two other small GTP-binding proteins involved in vesicle traffic (Ypt1p and ARF). Activation of GTPase was inhibited by an antibody to Sec23p but not by an antibody that inhibits the budding activity of the other subunit of the Sec23p complex. Also, activation was thermolabile in pure samples of Sec23p that were isolated from two independent sec23 mutant strains. It appears that Sec23p represents a new class of GTPase-activating protein because its sequence shows no similarity to any known member of this family. PMID- 8451645 TI - HTLV-1 provirus and mycosis fungoides. PMID- 8451646 TI - HTLV-1 provirus and mycosis fungoides. PMID- 8451647 TI - [Arthroscopic therapy of arthrofibrosis of the knee joint]. AB - Arthrofibrosis following ACL reconstruction is a well-recognized and disturbing complication. It may result in a greater functional deficit than the original ACL deficiency. The purposes of this retrospective study were to present our results of arthroscopic arthrolysis and gentle manipulation in 16 consecutive cases in the past almost 3 years, to determine and define the etiology and risk factors, to make recommendations regarding prevention and to develop a time-related management concept. All the 16 patients had previously undergone open ACL reconstruction and had developed arthrofibrosis. The average time from the index surgery to arthrolysis was 7.4 months (range 2.5-18.5 months) and the average follow-up was 17.6 months (range 6-38 months). After pathology-oriented arthroscopic debridement, notchplasty, cyclops resection etc., and following manipulation of the knee, range of motion was found to be improved in all cases at the final follow-up. The average of extension deficit was decreased from 20.0 degrees to 7.0 degrees and the flexion deficit from 34.4 degrees to 9.9 degrees. Only three patients regained normal range of motion compared to the other side. The only complication was an avulsion fracture of the fibula head which did not cause any lateral instability. No patient gained motion at the expense of joint stability. Patella baja was present in two and patellofemoral pain in seven cases at the final follow-up. Three patients underwent further surgery after the final follow-up. Arthrofibrosis, while having many causes, appears to be a preventable complication.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8451648 TI - [Arthroscopic sub-acromial decompression. Comments on indications and surgical technique]. AB - Between January 1989 and December 1991 614 arthroscopic subacromial decompressions were performed for impingement syndromes. The first 100 cases represented our learning curve. The first 74 of the remaining 514 cases were available for evaluation and form the basis of the results presented here. Twenty (27.02%) patients were rated stage II in Neer's classification and 54 (72.98%) were rated stage III, 33 (44.59%) of them with a small full-thickness tear (less than 1 cm) and 21 (28.37%) with larger defects. Patients were evaluated pre- and postoperatively utilizing the ULCA shoulder score. The average follow-up was 7.9 months. The overall results were satisfactory in 67 cases (90.5%) and unsatisfactory in 7 cases (9.5%). Within the satisfactory group, 28 results (37.8%) were rated excellent and 39 (52.7%) were rated good. In the unsatisfactory group four results (5.4%) were rated fair and three (4.1%) poor. The results in advanced stage III (n = 21), with an average follow-up of 8.4 months, were satisfactory in 20 cases (excellent in 8 and good in 12) and unsatisfactory in one case. It is concluded that arthroscopic subacromial decompression is an effective treatment for both stage II and III impingement syndromes, producing acceptable results that are comparable to those of open procedures. Technically, it seems necessary to perform synovectomy of the ventral synovia in the glenohumeral joint, to resect the coracoacromial ligament completely and also to remove calcifications completely. Depending on the findings of a preoperative sonographic examination of the shoulder joint, the extent of the acromioplasty may be minimized. PMID- 8451649 TI - [A surgical technical improvement of temporary bore wire fixation]. AB - The problems involved in temporary drilling wire fixation is described with reference to fracture of the humeral head as an example. The difficulties can be resolved with a developed drill bush. PMID- 8451650 TI - [Trauma score systems as instruments in quality control. A prospective study on validation of 7 trauma score systems with 612 trauma patients]. AB - Quality control in the treatment of trauma patients often consists in comparisons of survival rates. The trauma population under study is seldom defined with regard to severity of injury. Therefore crude survival rates are of little help when the quality of care is discussed. Trauma scores attempt to summarize the severity of injury of trauma patients in a single number. They attempt to translate differences in the severity of injury into a common language. This study tested the validity of seven common trauma score systems in the setting of Cologne in 1987. Six hundred and twelve trauma patients treated by physicians at the scene of the accident were prospectively followed up in 32 hospitals. Final diagnosis, treatment, complications, and survival were evaluated. Sensitivity and specificity in predicting survival were calculated for the following systems: Glasgow Coma Scale, Trauma Score, Revised Trauma Score, Injury Severity Score, TRISS, Prehospital Index, Polytraumaschlussel. The average time from emergency call to arrival of the emergency physician at the scene of the accident was 6.5 min. Four hundred and one patients (65.5%) were male. One hundred and thirty seven patients (22.4%) suffered from apnoea, 61 (10.0%) had a systolic blood pressure lower than 90 mmHg, 117 (19.1%) had had a cardiac arrest and 174 (28.4%) were unconscious. Four hundred and twenty-three patients (69.1%) left hospital alive. All trauma score systems tested showed sensitivities and specificities greater than 83%. They all proved their ability to classify trauma patients according to severity of injury. The TRISS performed best of all, with sensitivity of 93.1% and specificity of 93.7% at a cut-off point of 0.85.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8451651 TI - [Stress reactions and stress fractures in the high performance athlete. Causes, diagnosis and therapy]. AB - From 1987 until July 1991 70 athletes with stress reactions or stress fractures were treated in the orthopaedic department of the Hannover Medical School. The average age of the 42 male and 28 female athletes was 22.6 years. The number of athletes involved in track and field sports was 29 (41.4%), in gymnastics 9 (12.9%) and in soccer 5 (7.1%). The most common bone injured was the tibia in 29 (41.4%), followed by the tarsal navicular in 21 (30.0%), the midfoot in 17 (24.3%) and the fibula in 4 (5.7%) athletes. In three cases double stress fractures were found in adjacent locations; in one case a stress fracture of the opposite navicular occurred after the initial tarsal navicular stress fracture had healed, and in another case the tarsal navicular was found to be fractured again. Thirty-seven percent of the athletes claimed sudden increase in training intensity was the cause; 33% felt that the increased sprinting and jump activities were the reason for their complaints. In some athletes pain started after an ankle sprain. Standard diagnostic procedure consisted in X-rays in two planes and three-phase bone scanning. In tarsal navicular or tibial locations additional tomograms were performed. MRI and CT scans were reserved for unclear findings and to exclude the possibility of a tumorous or inflammatory process. A new grading system was introduced that covers all forms of stress reactions from periostitis to pseudarthrosis. Clinical symptoms, sport disabilities, radiological and bone scan findings were graded from A to D. Using a modified Wilson classification, all radiologically recognizable stress reactions could be classified.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8451652 TI - [Osteochondrosis dissecans tali. Results of surgical therapy]. AB - Surgical treatment with arthrotomic revision, removal of the subchondral sclerosis, and autologous bone transplantation with restoration of the cartilage layer resulted in good results in nearly 70%. This could be demonstrated in a follow-up examination in 26 of 38 surgically treated patients. The outcome is dependent on the patient's age at the onset of symptoms and the stage of the cartilage lesions. In adolescents, the results are better than in adults and better in cases without or with only mild cartilage lesions. The most important etiological factors seem to be biomechanical factors such as a sprained ankle- even without ligament ruptures. Osteoarthritis of the ankle joint is not a common sequela, and it occurs in only mild degrees in adult patients. PMID- 8451653 TI - [Arthroscopy of the upper ankle joint. List of indications from the literature- realistic expectations--complications]. AB - Based on the results of a retrospective study of 116 patients who underwent diagnostic and surgical arthroscopy of the ankle, we present the technique, the results, the complications, and the indications for ankle arthroscopy. The average age of the patients was 33 years (range 10-70 years). At follow-up the patients were examined clinically as well as radiologically. The results were scored for the criteria pain, function, athletic activity, walking aids, range of motion, and swelling. The overall score increased significantly from 50.1 preoperatively to 73.7 postoperatively (P < 0.05). The decrease in pain and the improvements in function and athletic activity after arthroscopy were significant. The other parameters (walking aids, range of motion, swelling) showed only slight changes. The patients' subjective assessment (visual analogue scale) also revealed a significant increase, from 35.6 to 69.5 (P < 0.05). After arthroscopy the preexisting radiologic lesions continued to progress. Some 71.2% of the patients suffered no limitations their work at follow-up but 13.6% reported slight limitations and 15.3% experienced moderate limitations. We documented severe restrictions in athletic activity; only 17% of the patients had maintained their previous level. In 16 cases we found iatrogenic temporary neurologic damage. PMID- 8451654 TI - [Reposition of fragments of the posterior surface of the vertebral edge with intraoperative ultrasound guidance]. AB - The question of whether fragments of the posterior vertebral surface have to be removed in every case remains to be answered. Nevertheless, in many cases it is important to establish the situation inside the spinal canal intraoperatively. To this end we have used intraoperative ultrasound in 21 cases. The results have always corresponded closely with the findings of preoperative and postoperative computed tomography. Under the influence of this method we have modified our operative procedure. The technique of intraoperative ultrasound and our current operative practice are described in the present paper. We use typical cases to show that intraoperative ultrasound of the spinal canal is a very useful technique for several reasons: Accurate depiction of the spinal canal is always possible without destabilizing the dorsal vertebral structures. The risks and disadvantages of intraoperative myelography are avoided. The method is easy and can be repeated as often as desired, an important advantage in checking the success of the removal of fragments and in reviewing the situation after transpedicular cancellous bone grafting. PMID- 8451656 TI - Keep your words from falling. PMID- 8451655 TI - [Allogeneic cruciate ligament replacement. Perspectives and initial clinical results]. AB - There is a continuing search for the ideal substitute for the cruciate ligaments. Autogenous tissues have been widely used as a replacement. The use of allografts is an attractive alternative: no donor side morbidity, decreased operative time, smaller incisions, especially with new endoscopic techniques, unlimited supply with a choice of graft sizes in multiple ligament reconstructions and a long shelf-life are some of the distinct advantages that allografts offer. They may be useful in circumstances where there is no suitable autologous substitute or the available tendon is too short to span the joint cavity. The preparation of an allograft requires appropriate donor selection and screening, careful surgical tissue procurement, and safe and effective processing techniques. At the present time, the issue of secondary sterilization of allografts remains controversial. Subclinical immune response and the possibility of transmission of infectious agents have to be considered. The early results in the literature and in our small series are encouraging; however, long-term results are necessary prior to widespread use of allografts in cruciate ligaments reconstructions. The authors believe that allografts should presently be reserved for use as an alternative to prosthetic ligaments in situations where autografts are unavailable or inappropriate. PMID- 8451657 TI - Urinary incontinence in the elderly: not a normal part of aging. PMID- 8451658 TI - The use of a pain diary in patients with advanced cancer of the prostate. PMID- 8451659 TI - When your first pediatric urology patient dies. PMID- 8451660 TI - Jell-O meds. PMID- 8451661 TI - Sex and interstitial cystitis: explaining the pain and planning self-care. PMID- 8451662 TI - Breast cancer after mammary augmentation. AB - Augmentation mammoplasty has been said to reduce the risk for subsequent development of mammary gland carcinoma, but it may confer a worse prognosis should breast cancer develop. Nine patients who had breast cancer after augmentation mammoplasty were treated at the Ochsner Foundation Hospital and Clinic. The mean interval between augmentation and the development of a palpable mass was 6.8 years (range, 2 to 20 years). Four patients were treated with modified radical mastectomy, one was treated with radical mastectomy, and four were treated with tylectomy, axillary dissection, and radiotherapy. One of the four treated with tylectomy required salvage mastectomy. Reconstructions were done in all except one mastectomy patient. Five patients had stage I disease and four had stage II disease at the time of diagnosis. Over a mean follow-up of 4.75 years from the time of diagnosis of carcinoma of the breast, three of the four patients with stage II disease have either had recurrent disease or died of breast cancer, and one of the patients with stage I disease died with hepatic metastases. Mammography was not found to be useful for the detection of masses after augmentation mammoplasty. Needle aspirations were useful for diagnosis of nodal disease outside the breast, but not helpful in diagnosis of the breast lesion proper. Our analysis suggests that breast augmentation and the patient's psychologic considerations may delay the diagnosis of breast cancer. Additionally, patients may fare worse when breast cancer develops after mammary augmentation. We recommend preoperative mammography in most patients before mammary augmentation, particularly in those over the age of 30 years and those with a family history of breast cancer. PMID- 8451663 TI - Primary immunization series for infants: comparison of two-component acellular and standard whole-cell pertussis vaccines combined with diphtheria-tetanus toxoids. AB - At 2 months of age, 145 infants were randomized to receive either a two-component acellular pertussis vaccine [lymphocytosis-promoting factor (LPF)/filamentous hemagglutinin (FHA)] or standard whole-cell pertussis vaccine, each combined with diphtheria-tetanus toxoids, as their primary immunization series. Of the 132 subjects (91%) who completed the study, those receiving the acellular vaccine had significantly fewer adverse reactions: 5% vs 30% (local) and 17% vs 30% (systemic, including fever). During the first 24 hours acetaminophen usage, a general measure of adverse reactions, was lower in the test group. Overall, 35% of the acellular vaccine doses were reaction free vs 12% of the whole-cell doses. No serious reactions occurred in either group. Antibody responses to LPF and to FHA were significantly increased after the second and third immunizations with the test vaccine and were consistently higher than levels achieved with the standard vaccine. Thus the two-component acellular pertussis vaccine was associated with fewer adverse reactions and improved serologic responses to LPF and FHA as compared with the currently recommended whole-cell vaccine. PMID- 8451664 TI - Risk of HIV infection in the homeless and chronically mentally ill. AB - Recent data suggest that the homeless and those with chronic mental illness may be at increased risk for HIV infection. A review of the recent literature reveals insufficient rigorously collected data to identify with confidence any particular subgroup of chronically mentally ill patients at increased risk. Nonetheless, it seems reasonable to suspect that those with acute psychosis, a history of substance abuse, or a history of sexual abuse may be at higher risk. Conversely, some data currently support the conclusion that homeless persons are at increased risk for infection due to human immunodeficiency virus (HIV). Clinicians of all disciplines should be aware of these findings and be particularly vigilant when patients are members of both aforementioned groups. Future research should focus upon improving service delivery to the homeless and mentally ill, particularly with regard to sex education and substance abuse intervention. Also, continued research into causal influences of homelessness will ultimately lead to more definitive intervention. PMID- 8451665 TI - Fine needle aspiration as a means to cost-effective health care. AB - Public opinion, the federal government, and financial constraints are demanding that the cost of medical care be controlled. Physicians are keenly aware of this problem. We believe that the contribution of fine needle aspiration to cost containment has not yet been fully recognized. We advocate fine needle aspiration as the initial diagnostic procedure on any palpable lesion. We present some cases from our daily practice diagnosed by this simple technique, with the aim of demonstrating how it can help clinicians and surgeons to achieve their goal of accurate and prompt diagnosis with less expense to the patient. PMID- 8451666 TI - Lipid management program: results of applying national guidelines in a private practice. AB - In our large single-specialty cardiology practice, we implemented a lipid management program based on the recommendations of the Expert Panel of the National Cholesterol Education Program and the Helsinki Heart Study. This program used allied health professionals and customized computer software to deliver efficient, comprehensive care to the 1214 patients enrolled in the program after 33 months. Data are reported for the 543 patients enrolled for more than 1 year. Cholesterol data were analyzed for all patients whose initial triglyceride values were less than 400 mg/dL. For this group of patients, the mean cholesterol level decreased from 242.7 to 217.4 mg/dL, triglycerides fell from 170.0 to 144.7 mg/dL, HDL cholesterol increased from 41.6 to 42.9 mg/dL, and LDL cholesterol fell from 167.2 to 145.7 mg/dL. Using guidelines modified from the National Cholesterol Education Program, a significant number of patients were able to achieve desirable LDL and HDL goals. Modified national guidelines can be used effectively in a private practice setting. PMID- 8451667 TI - Vulvar ulcerations in girls with myelocytic leukemia. AB - To determine the prevalence of vulvar ulcerations in girls with myelocytic leukemia receiving chemotherapy, we reviewed the records of 108 patients. At the time of diagnosis, 69 patients were prepubertal, and the remaining 39 patients were postpubertal. Genital ulcerations were seen in 11 girls (10%), all of whom were white and postpubertal. None of the prepubertal girls complained of vaginal bleeding or had vulvar or vaginal ulcers. The findings suggest that genital ulcerative lesions occur primarily in postpubertal girls, probably because of the distinctive changes that occur during puberty as a result of estrogen stimulation. PMID- 8451668 TI - Noninvasive visualization of coronary arteriosclerosis by computed tomography. AB - I report a new, extremely rapid, noninvasive technique for the diagnosis of coronary artery occlusion. An ultrafast x-ray cine-computed tomographic scanner (cine-CT) allows visualization of the coronary arteries without injection of contrast material. The arteries can be seen because of the CT contrast between blood in the arteries and the pericardial fat. This theory is supported by a study of 200 patients followed up for 5 years. This examination is extremely short and noninvasive, so it is a potentially efficient method of mass screening for coronary arteriosclerosis. PMID- 8451669 TI - Gastric carcinoma among younger individuals in Mississippi. AB - During a time when gastric cancer in the United States appears to be decreasing in incidence and occurring primarily in older individuals, a 12-year review of our experience (1977 to 1989) has identified a disproportionate number of gastric cancers in the young black population. In this series of 97 patients with gastric adenocarcinoma, the mean age at diagnosis was 58 years (range, 22 to 84 years). There were 54 men (56%) and 43 women; 78 (80%) were black, 17 (18%) were white, one was American Indian, and one was Mexican. Fifty-two patients (54%) had stage IV disease at the time of presentation. Fifty-two patients (54%) were less than 60 years old at diagnosis; 45 (86%) of these were black men. We do not know the reason for this unusual age distribution, but a combination of environmental factors or an unusually susceptible population may be involved. Identification of a gastric ulcer in this cohort warrants careful follow-up and appropriate treatment. PMID- 8451670 TI - Cardiovascular anomalies in Marfan's syndrome: the role of echocardiography and beta-blockers. AB - Six patients with Marfan's syndrome were included in a study to determine the effect of beta-blockers on progressive aortic dilation. Patients' histories and results of physical examination, chest radiogram, electrocardiogram, and echocardiogram are reported. Patients ranged in age from 5 years 8 months to 14 years; one was black, five were white, and four were male. The study included a brother and sister whose mother had had Marfan's syndrome and died at age 32. All six patients had aortic dilatation documented by echocardiography; two also had mitral valve prolapse. Auscultatory findings were unrevealing, but patients showed easy fatigability. During the prospective, randomized study, half of the patients were given beta-blockers; the other half formed a control group. Findings at short to midterm follow-up suggest that beta-blockers are beneficial in arresting progressive dilatation of the aorta. PMID- 8451671 TI - Diabetic wound healing and limb salvage in an outpatient wound care program. AB - Healing wounds and preventing amputations in diabetic patients is a challenge. Baptist Hospital in Nashville, Tennessee, developed an outpatient Wound Care Center program to treat patients with chronic wounds. This comprehensive program includes wound assessment, vascular studies, revascularization, antibiotic therapy, wound debridement, a topical growth factor solution of platelet-derived wound healing factors, protection devices, and patient education. A retrospective study of wound healing and limb salvage was conducted on 54 diabetic patients with 86 wounds. Average previous wound duration was 8 months. Amputation had previously been recommended for 15 limbs. Healing occurred in 88% of the wounds in an average of 15.8 weeks. Ninety-three percent of the limbs for which amputation had been recommended were salvaged. Healing efficacy and amputation reduction have been demonstrated in this program. PMID- 8451672 TI - Syringe and needle exchange programs: Part I. AB - Syringe and needle exchange (SANE) programs appear to be a pragmatic approach to reducing the rising incidence of human immunodeficiency virus (HIV) infection among intravenous drug users (IVDUs). One purported indication of the effectiveness of SANE programs is lower prevalence rates of cases of AIDS or of HIV seropositivity in cities with SANE programs than in cities without such programs. In each positive comparison cited, however, the lower levels of HIV seropositivity were already present before the establishment of SANE programs. A second indicator of SANE effectiveness is a reduction in prevalence of hepatitis B in SANE program participants. Multiple factors working in concert, not simply the SANE programs, however, account for such progress; such factors include reductions in sharing of uncleaned injection equipment; legal exchange or sale of syringes at pharmacies; regular rinsing of used "works" with bleach; and epidemiologic fluctuations in the prevalence or a saturation level of the hepatitis B virus in IVDUs. A third indicator of the value of SANE programs is that they enable some otherwise unreachable IVDUs to make contact with a social or health facility. SANE programs do not facilitate the induction of new IVDUs or increase the frequency of injection by older addicts. From 60% to 90% of SANE attenders will return borrowed used injection equipment. Most participants reported that they reduced the frequency of lending or borrowing unclean injection equipment. Counterbalancing the above, SANE programs attract only a minority of all IVDUs in most cities, and they fail to attract the youngest subset of IVDUs. The attrition rate is high; only a small percentage of attenders remain with the program for more than a few months. Although many of the initial concerns about SANE programs have not been realized and there have been important public health gains to those who continue to attend them, SANE programs deserve more careful, unbiased, longitudinal research before they are established on a wide scale in the United States. PMID- 8451673 TI - Syringe and needle exchange programs worldwide: Part II. AB - The first large-scale syringe and needle exchange (SANE) programs were established in The Netherlands and in the United Kingdom (UK) about 8 years ago. Since then, SANE programs have been established in Australia, Sweden, Canada, and the United States. To date, the most useful data concerning the impact of these programs have come from studies in the UK and from New Haven, San Francisco, Tacoma, and New York City in the US. Successful SANE programs require careful planning; those in charge should be familiar with the accomplishments, problems, and goals of established programs. Advance publicity and involvement of community activists, the local police precinct, and ward or district politicians are imperative for overcoming misunderstandings and prejudices and fostering a team approach. Pilot projects must be adequately funded. Other requirements include accessible facilities, convenient hours of operation (including evening hours), provision of mobile units if at all possible, and provision for sanitary disposal of discarded injection equipment in the neighborhood around the SANE programs. Programs also should have a strong evaluation component, preferably staffed by an independent university-affiliated research center. Periodic site visits are necessary to ensure that services promised in the protocol are actually delivered not only initially, but also over time. Problems with security and drug dealing in and around the building where the SANE program is located are likely, and appropriate measures should be taken to counter them. PMID- 8451675 TI - Carbon monoxide poisoning in infants: treatment with hyperbaric oxygen. AB - Since 1974 the United States Air Force has treated more than 300 cases of carbon monoxide poisoning with hyperbaric oxygen (HBO). Fourteen of the patients treated were younger than 2 years of age. In all but one case, poisoning resulted from a faulty home heating unit; in all but two cases, more than one family member was affected. There was complete recovery in 13 of the 14 infant patients. The pathophysiology, presentation, and clinical management of carbon monoxide poisoning in infants is discussed. PMID- 8451674 TI - Evaluation of cefixime in the treatment of bacterial maxillary sinusitis. AB - The efficacy and safety of cefixime, the first oral third-generation cephalosporin, were evaluated in a multicenter clinical trial involving 118 adult patients with acute sinusitis or acute exacerbations of chronic sinusitis. Patients received a single daily dose of 400 mg of cefixime for a mean duration of 10 days; 106 patients completed a course of therapy. Clinical cure and improvement were achieved in 90% of these patients (61% cured and 29% improved). Among the patients evaluated again 2 weeks after therapy, 91% had a sustained clinical cure or improvement. Sinus exudate specimens were obtained from all patients by transantral puncture before therapy. Pathogens were isolated from 76 patients (66%), the most common pathogens being Haemophilus influenzae, alpha hemolytic streptococci, and Streptococcus pneumoniae. Eighty-six percent of pathogens were presumed eradicated. Three patients discontinued therapy because of side effects. The most frequently reported adverse effects were gastrointestinal, with 20% of patients reporting diarrhea. Cefixime was effective in the treatment of bacterial sinus infections in adults and was well tolerated. PMID- 8451676 TI - Low-cost screening mammography: results of 21,141 consecutive examinations in a community program. AB - The benefits and problems of comprehensive screening mammography are well recognized. Using the advantages inherent in a unified medical community, we designed a low-cost screening program with emphasis on prompt work-up, continuity, and conservative management of lesions with low probability of being malignant. Its goals were to duplicate the good results of previously reported breast screening programs as measured by detection and biopsy rate and the histologic and staging analysis of cancers found, while minimizing the recognized problems of aggressive screening. This paper describes our program and reports our first three years' experience as represented by 21,141 consecutive mammograms. Analysis suggests that our goals have been met. We have gained lay and community acceptance, and our results appear in line with those of other successful screening series. PMID- 8451677 TI - Clinical uses of pimozide. AB - One of the more difficult psychopharmacologic aspects of current clinical psychiatry is finding a neuroleptic drug that adequately treats delusional states. Furthermore, many chronic schizophrenics remain resistant to standard antipsychotic medication, and clozapine is effective in only 30% to 50% of refractory cases. In addition, clozapine has several serious side effects and is expensive. We have determined that pimozide is clearly effective in Tourette's syndrome, maintenance schizophrenia, and some delusional disorders. We further demonstrate that the drug is likely to be effective in the treatment of the negative symptoms of schizophrenia and other delusional states. In addition, we suggest that a trial of pimozide may be indicated before giving clozapine to treatment-resistant schizophrenic patients. The side effect that probably most limits pimozide's current use is the possible production of ECG abnormalities. This side effect does not seem to be a realistic clinical concern, however, if the patients are properly screened and the pimozide dose is maintained at or below 20 mg/day. PMID- 8451678 TI - Fungemia due to Torulopsis glabrata. AB - Torulopsis glabrata is a yeast ordinarily considered nonpathogenic. Systemic infection with this yeast occurs in patients who are debilitated, immunosuppressed, diabetic, or receiving multiple antibiotics. We have presented a case of fungemia due to T glabrata in a previously healthy person. The predisposing condition resulting in debility and predisposition to fungemia was major vascular surgery. Treatment with amphotericin B eradicated the fungemia. PMID- 8451679 TI - Use of endoscopic ultrasonography for evaluation of painless jaundice. AB - Precise preoperative evaluation and staging of cases of painless jaundice is extremely important. Many of the patients are older and may have multiple medical problems that increase their operative risk. Assessment of the distal common bile duct, ampulla of Vater, and head of the pancreas is particularly difficult. Various imaging modalities are available but are not sensitive enough to detect small lesions or local invasion. Endoscopic ultrasonography is a new technique that places the transducer closer to the organ being evaluated, adding a new dimension to defining tumor invasion and extension. PMID- 8451680 TI - Beneficial effect of epidural anesthesia on oxygen consumption in a parturient with adult respiratory distress syndrome. AB - Multifactorial increases in oxygen consumption during labor may exceed available oxygen supply. Cumulative subclinical oxygen debt could be clinically detrimental to both patient and fetus. We have reported the use of continuous mixed venous oxygen saturation monitoring to identify changes in oxygen consumption after painful uterine contractions in a critically ill parturient. We used continuous venous saturation monitoring to document the effects of epidural analgesia on oxygen balance in our patient. The absence of venous desaturation with contractions after abatement of labor pains confirmed that pain was the major cause of increased oxygen consumption in this critically ill parturient. Broader use of mixed venous saturation monitoring may allow detection of oxygen deficits during labor and direct appropriate therapy in other critically ill parturients. Similar applications and results have been noted for other disease states in nonpregnant patients. PMID- 8451681 TI - McCune-Albright syndrome: how many endocrinopathies can one patient have? AB - In this one patient with McCune-Albright syndrome are seen a multitude of endocrinopathies--more than in any case previously described. Only fibrous dysplasia with cafe-au-lait spots and/or endocrine hyperfunction are required for the diagnosis of the syndrome. Our patient has polyostotic fibrous dysplasia, cafe-au-lait spots, and at least four primary endocrinopathies. She had shown precocious puberty (with an ovarian follicular cyst later requiring resection), hyperthyroidism due to toxic nodular thyroid disease, primary hyperparathyroidism, and hyperprolactinemia (with associated hypogonadotropic hypogonadism and premature menopause). With this many organs involved in the same patient, it is hard to imagine that a genetic defect will not soon be identified as the unifying cause of the entire syndrome. PMID- 8451682 TI - Should due process be part of hospital peer review? PMID- 8451683 TI - Should pregnant urban south African women be screened for hepatitis B? AB - The prevalence of hepatitis B virus (HBV) infection in the South African urban obstetric population, which consists of white, black, coloured and Asian patients from different socio-economic, cultural and geographical backgrounds, is unknown. Routine screening performed in 3,469 urban pregnant women revealed that 42 patients were HBV surface antigen-positive (a prevalence of 1.21%). Only 2 patients (4.6%) were hepatitis B e antigen (HBeAg)-positive (0.06% of the entire cohort), whereas the remaining 40 were identified as hepatitis B e antibody positive. Despite a significant increase in the numbers of black patients, there has not been an accompanying increase in the number of HBV carriers. Replicative infection was equally distributed among white and black pregnant women. Because the low prevalence of HBeAg results in lack of perinatal transmission and the prevention of a single case of neonatal hepatitis B infection is costly, we conclude that in South African urban hospitals, routine screening for hepatitis B is not cost-effective. PMID- 8451684 TI - Abnormal peri-operative haemorrhage in asymptomatic patients is not predicted by laboratory testing. AB - The pre-operative identification of individuals at high risk of bleeding during major elective surgery is obviously important. Extensive haemostatic screening is, however, expensive and may be inappropriate in low-risk groups. Accordingly, we undertook two studies to determine whether it could be justified in patients without a history of abnormal bleeding. In the first of these, 45 of 159 patients were excluded because of aspirin ingestion and a further 3 because of positive bleeding history so that prothrombin time, activated partial thromboplastin time, bleeding time and platelet count were measured in 111 asymptomatic patients about to undergo major surgery. A single patient had mild thrombocytopenia, and 8 had a prolonged partial thromboplastin time; none showed abnormal peri-operative haemorrhage. In the second study, over a 4-month period, 49 patients out of 1,872 required larger peri-operative blood transfusions than anticipated; on investigation, none of these patients was shown to have disturbances in haemostatic mechanism, the transfusion having been indicated for technical reasons. Patients undergoing elective surgery should be asked about medication and previous bleeding and if they have no history thereof and a physical examination is negative, pre-operative screening for coagulation defects would appear to be unnecessary. PMID- 8451685 TI - Morbidity from falciparum malaria in Natal/KwaZulu. AB - Plasmodium falciparum malaria is endemic in the northern KwaZulu areas of South Africa. The clinical morbidity produced by this parasite has not been studied since the institution of the present malaria control programme. Fifty-nine patients were prospectively studied at a peripheral clinic during the peak malaria season; symptoms and signs of the infection, parasite loads, haemoglobin values and leucocyte counts were recorded in all patients. Haemoglobin and leucocyte counts were also measured in 37 control subjects without malaria. The commonest symptoms were persistent headache (100%), rigors (98%) and myalgia (93%). None of the patients presented with coma, pulmonary oedema, hypoglycaemia or algid malaria. Splenomegaly was found in 49%, hepatomegaly in 20% and mental confusion in 5% of patients. Mean parasite load was 1.71% and 57% of patients had parasite loads of < 1%. Anaemia of < 10 g/dl was significantly more frequent (P < 0.0001) in the patient group than in the control group. Leucopenia (white cell count < 4.0 x 10(9)/l) was present in 12 of 50 patients in whom it was measured compared with 2 controls (P = 0.0175). The results show a wide range of morbidity, without severe complications as presenting manifestations. Symptomatic infection in the presence of low parasite loads suggests that there may be little or no immunity in this population. PMID- 8451686 TI - Determination of the functioning of autotransplanted parathyroid tissue in muscle. AB - Twenty dialysis and renal transplant patients with parathyroid hyperplasia underwent a total parathyroidectomy and an autotransplantation in forearm muscle. Twelve patients were available for investigation of the function of the transplanted parathyroid tissue. Differential studies of the two arms revealed functioning of the transplanted tissue in all cases. This was more readily demonstrated by determining the intact hormone in both arms. PMID- 8451687 TI - Evaluation of rapid enzyme immunobinding assays for the detection of antibodies to HIV-1. AB - Three rapid enzyme immunobinding assays, Abbott's TestPack HIV-1/HIV-2, Clonatec's Rapid HIV1/HIV2 AB and the DuPont HIVCHEK 1 + 2, were evaluated using a panel of 20 selected sera with Western blot-proven reactivity to at least one envelope glycoprotein of HIV-1. The Abbott assay had the highest sensitivity and detected 18 of the 20 sera with no indeterminates (i.e. specimens with high background coloration which interferes with interpretation of the assay). Both the Clonatec and DuPont rapid assays correctly identified 12 sera as HIV-1 antibody-positive; the former produced 5 false-negatives and 3 indeterminates and the latter 7 false-negatives and 1 indeterminate. The majority of the sera used in the evaluation showed evidence of early sero-conversion as many had low absorbance ratios in a screening enzyme immunosorbent assay. Although they represent only a small portion of clinical specimens, they point to the need for careful evaluation of new methodologies, using appropriate, well-characterised sera, before such techniques are accepted for general use. PMID- 8451688 TI - The cardiovascular and intracranial effects of laryngoscopy and endotracheal intubation in hypercarbic neonatal piglets. AB - Laryngoscopy and endotracheal intubation is a potent sympathetic stimulus in adults. Neonates are frequently intubated, but few data exist on the cerebral effects of this intervention. The cardiovascular and intracranial effects of laryngoscopy and endotracheal intubation were studied in 17 hypercarbic neonatal piglets. The mean arterial pressure in the study group (11 piglets) increased significantly within 2 minutes of the stimulus, and remained elevated for almost 14 minutes. The intubated animals showed significantly more haemorrhage in the basal area of the brain than the 6 control animals. The distribution suggests bleeding in the choroid plexus of the 4th ventricle. The significance of such bleeds is not immediately apparent, since none of the animals was grossly neurologically affected by the intervention. However, subtle long-term neurological deficits cannot be excluded and this aspect requires further study. Laryngoscopy and endotracheal intubation may cause non-lethal haemorrhage in the choroid plexus and central canal of the hindbrain in hypercarbic, neonatal piglets. PMID- 8451689 TI - Dose-dependent effects of exogenous gonadotrophins on the endometrium of the rat. AB - We compared the serum levels of oestrogen and progesterone and the endometrial morphology of normal pregnant rats at 5,5 days' gestation with those of pregnant rats given either low (10 IU) or high (20 IU) doses of two gonadotrophins: follicle-stimulating hormone (FSH) and human chorionic gonadotrophin (HCG). Evidence of ovarian hyperstimulation was observed in the high- but not the low dose group; both treatment regimens caused significant changes in the endometrial surface, epithelial height, the microvillous border, the glycocalyx, the subepithelial stromal cells and the mitotic activity of the surface epithelial and stromal connective tissue cells. The effects of the high-dose treatment were more severe than those of the low-dose treatment. The serum oestradiol and progesterone levels of the treated groups were not significantly different from those of the control group. The changes in the endometrium after both treatment regimens may interfere with normal trophoblastic-endometrial interactions and could influence the maintenance of pregnancy. This investigation demonstrated that even low doses of gonadotrophins, which do not cause obvious ovarian stimulation, affect uterine morphology. The findings have important implications for in vitro fertilisation and embryo transfer programmes. PMID- 8451690 TI - Malaria prophylaxis--the South African viewpoint. AB - A consensus meeting was held under the auspices of the Department of National Health and Population Development in September 1991 in order to establish local, current consensus on malaria prophylaxis for the South African traveller within South Africa and neighbouring African countries. The meeting was attended by malaria experts and others interested in malaria. The consensus reached took into consideration not only the international literature, but also local clinical experience and viewpoints. As a result, it was decided that prevention of mosquito bites is the mainstay of malaria prophylaxis and that chemoprophylaxis should be individualised. Malaria may still be contracted despite good compliance with the recommended prophylactic regimen. PMID- 8451691 TI - Infant drownings in nappy buckets. PMID- 8451692 TI - Corneal transplantation from an HIV seroconverting donor. PMID- 8451693 TI - Action on food labelling. PMID- 8451694 TI - Action on food labelling. PMID- 8451695 TI - Plasma concentration after instilling 2% lignocaine gel into the urethra. PMID- 8451696 TI - Follow-up on AIDS at Hottentots Holland Hospital. PMID- 8451697 TI - A policy proposal to manage chronic diseases of lifestyle in South Africa. PMID- 8451698 TI - Treatment of Rett's syndrome with bromocriptine. PMID- 8451699 TI - Dairy products, allergy and atherosclerosis. PMID- 8451700 TI - Conduct disorder and subacute sclerosing panencephalitis. PMID- 8451701 TI - Endovascular treatment of an external carotid arteriovenous malformation. PMID- 8451702 TI - [Plasma melatonin concentrations as additional biochemical markers for ovulation]. PMID- 8451703 TI - Preventing malaria. PMID- 8451704 TI - Malaria--are we giving travellers adequate and accurate information? PMID- 8451706 TI - Medicine in Malawi. PMID- 8451705 TI - Transfusion of malarial or other parasites in blood. PMID- 8451707 TI - Lessons from the 1992 measles epidemic in South Africa. PMID- 8451708 TI - Paediatric surgery in the RSA--practice and training. AB - A survey of the current practice of general paediatric surgery in South Africa and Namibia was conducted by means of a postal questionnaire. One hundred and eighty-one replies were obtained (52%). Analysis showed that although surgeons are located predominantly in the major cities, 18% practised in the larger towns or rural areas. Although paediatric surgery represents a small volume of their work, most surgeons do attend to the surgical needs of children. The majority of surgeons have received some paediatric surgical training but this was considered inadequate by nearly half of all surgeons and by 60% of those who qualified in the last 10 years. Current postgraduate training at most of our universities involves a 3-6-month rotation, but from our survey this is considered insufficient in practice and there appears to have been some deterioration in paediatric surgical training in recent years. Steps needed to maintain paediatric surgical standards are discussed. PMID- 8451709 TI - Transplantation for diabetic nephropathy at Groote Schuur Hospital. AB - Over a period of 6 years, 9 patients with diabetic nephropathy received renal allografts at Groote Schuur Hospital. This low figure represents 2.8% of the total number of renal transplants done at our institution, and is evidence of concern about the apparent poor results of transplantation in these patients. After 2 years, patients and graft survival rates in diabetics were 87% and 62% respectively. Vascular disease was a major problem. Six patients developed limb gangrene, and symptomatic coronary and cerebrovascular disease developed in 2 patients. Infections were common and included wound sepsis, cellulitis, candidiasis and urinary tract infections. Diabetes was poorly controlled after transplantation in 5 patients. Proliferative retinopathy was present in 6 patients but remained stable after transplantation. Despite very strict selection criteria, the results of renal transplantation in diabetic patients remain poor. Better treatment strategies are needed to justify acceptance of these patients for transplantation. PMID- 8451710 TI - Public attitudes to organ donation in South Africa. AB - Public attitudes to organ donation may be influenced by cultural beliefs as well as racial prejudices and superstitions. In South Africa we are able to examine these issues from both a First- and a Third-World perspective. In this study the attitudes of 1 299 urban white, 625 rural black and 826 urban black South Africans were examined. Eighty-nine per cent of white, 84% of rural black and 76% of urban black South Africans are prepared to donate their own organs. All groups are less willing to donate the organs of close relatives (76% white, 76% rural black and 67% urban black). Most people felt that this decision should be made by the person before death. Most black people (88%) felt that the race of both donor and recipient were irrelevant. Only 23% of black people were prepared to donate their corneas, compared with the 69% and 70% willing to donate their kidneys and heart respectively. PMID- 8451711 TI - Corynebacterium group D2 urinary tract infection. AB - An unusual multiply resistant corynebacterium was isolated from the urine of a comatose patient. This organism was resistant to sulphafurazole, trimethoprim, nalidixic acid, cefazolin, nitrofurantoin, clindamycin, erythromycin, oxacillin, penicillin, gentamicin, amikacin, cinoxacin, ceftazidime and cefotaxime, but was susceptible to ciprofloxacin, ofloxacin, norfloxacin, vancomycin and fucidin. It was identified as the first reported isolate in South Africa of corynebacterium group D2, an organism recently implicated in alkaline-encrusted cystitis and urinary tract infection. We discuss the case history of the patient and review the literature. PMID- 8451712 TI - Degloving injuries and flap viability assessment. AB - Degloving injuries are associated with major morbidity. The management of these injuries is still not resolved. The method of management used by the authors involves the harvesting of split skin from the surface of the flap and assessment of flap viability based on surface dermal capillary bleeding. The skin grafts are then used to cover denuded areas. This technique has proved to be effective, time saving and morbidity-reducing in the cases reviewed here and in recent publications. The issue addressed in this trial was the effect of partial de epithelialisation on the survival length of a flap. Two groups of dorsal rat flaps were compared. In one group, the flaps were raised and restitched after a period of time and in the second group, the surfaces of identical flaps were partially de-epithelialised and then restitched. The survival length of these flaps was compared, as well as the metabolic responses to surgery in the two groups. No statistically significant differences were found in these 2 groups. It was concluded that partial de-epithelialisation did not have a detrimental effect on duration of flap length survival, thus encouraging the continued use of the clinical technique described above in the handling of degloving injuries. PMID- 8451713 TI - Percutaneous transluminal angioplasty for the M2 portion vasospasm following SAH: development of the new microballoon and report of cases. AB - A new silicone microballoon was developed for the percutaneous transluminal angioplasty of smaller intracranial vessels, such as A1, A2 and M2. This balloon was 0.5 x 2.0 mm in the deflated condition and became 2.2 x 6.5 mm inflated with 0.02 mL of fluid, and its bursting pressure was 2 atm. Two illustrative cases are presented. The first case was not treated in the M2 distribution. The second case of vasospasm of the left M2 portion was successfully treated with this new balloon, with prompt improvement of the neurological condition and cerebral circulation. The usefulness of our microballoon in treating a patient with vasospasm of small intracranial arteries is discussed. PMID- 8451714 TI - The role of transsphenoidal microsurgery in the management of sellar and parasellar meningioma. AB - We report on eight meningiomas that have been operated on via the transsphenoidal route since May 1988. Six patients harbored cavernous sinus meningiomas with intrasellar extension. The intrasellar tumor extension and the parasellar tumor portion medial to the carotid artery were removed. Decompression of the pituitary gland with normalization of prolactin levels was achieved in all patients. It is a well-tolerated approach to confirm the diagnosis and still allows the option of major transcranial surgery in the event of tumor progression. Additionally, we report complete tumor removal in two rare cases with intrasellar and suprasellar merely subdiaphragmatic meningiomas. PMID- 8451715 TI - Successful total removal of intramedullary hemangioblastoma from the medulla oblongata. AB - The case of a large solid hemangioblastoma embedded wholly in the medulla oblongata is reported. Preoperative magnetic resonance imaging provided precise indications of the anatomical location and radiologic features of the tumor, which facilitated its total removal by microsurgery. Short-latency somatosensory evoked potentials were monitored throughout the operation. PMID- 8451716 TI - Noonan phenotype associated with intracerebral hemorrhage and cerebral vascular anomalies: case report. AB - A case of a 19-year-old man with multiple characteristics of the Noonan phenotype and a massive intracerebral hemorrhage in the left putaminal region is presented. The hemorrhage was removed surgically, and the patient made a good recovery and was finally able to walk unassisted. Postoperative cerebral angiograms revealed various vascular anomalies, including a small aneurysm. To the best of our knowledge, this is the second detailed case report of an association of the Noonan phenotype with cerebral vascular anomalies presenting intracerebral hemorrhage. The etiology of this syndrome remains unknown but the possible causes of this rare association are discussed. PMID- 8451717 TI - The MRI and CT evidence of primary brain stem injury. AB - A 61-year-old man made a good recovery from posttraumatic right hemiparesis and prolonged disturbance of consciousness. Computed tomography (CT) showed a hematoma in the interpeduncular cistern. Magnetic resonance imaging (MRI) pinpointed an injury between the left cerebral peduncle and the reticular formation. Apart from contusion, the mechanism of injury may have been disruption of the paramedian branches of the basilar artery as the brain stem impacted on the clivus during the traffic accident. In contrast with reported autopsy findings that brain stem injury must be associated with severe supratentorial brain trauma (Adams et al., Brain 1977; 100:489-502), this case suggests that primary brain stem injury may occur and run a benign course. PMID- 8451718 TI - Multiple sinus pericranii with systemic angiomas: case report. AB - The authors report the case of an adult male who had multiple sinus pericranii, as well as angiomas in the retina and the skin of the knee. Although sinus pericranii is well documented, a simultaneous involvement in as many as four separate regions has not been reported. Clinical, radiographic, and histopathological features are detailed. Implications for the role of surgery and management is discussed. PMID- 8451719 TI - Giant intracranial mucocele secondary to osteoma of the frontal sinuses: report of two cases and review of the literature. AB - Two cases are reported in which the growth of an osteoma of the frontal sinuses led to the formation of a secondary lesion, an intracranial mucocele, with marked mass effect. PMID- 8451720 TI - Extradural spinal angiolipoma: report of a case studied with MRI. AB - The current report describes a case of extradural angiolipoma with spinal cord compression that was studied by magnetic resonance imaging. In considering the strategy for the surgical management, it is desirable to determine the histologic type of spinal cord tumors before the operation. The literature of spinal angiolipoma is reviewed, and the possibility of using magnetic resonance imaging to define the histologic type of spinal cord tumors before operation is discussed. PMID- 8451721 TI - The rape of the spine. PMID- 8451722 TI - Dissecting aneurysm of the anterior cerebral artery: report of two cases. AB - Two cases of spontaneous dissecting aneurysm localized to the anterior cerebral artery are reported. Both patients experienced severe headaches, followed by symptoms of cerebral ischemia. In the first case, the dissecting aneurysm showed an angiographic appearance resembling a saccular aneurysm of the anterior communicating artery, and the diagnosis of dissecting aneurysm was confirmed at operation. The second case was treated conservatively, and the diagnosis was reached by repeat angiographic studies. PMID- 8451723 TI - Spontaneous midbrain hemorrhage: report of seven new cases. AB - Spontaneous midbrain hemorrhage is a unique brain-stem vascular lesion. Sixty-six cases have been reported in the literature, to which we add seven. Of the total of 73 patients reviewed, most presented acutely (66%), but subacute (22%) and chronic onsets (12%) also occurred. Neuro-ophthalmologic abnormalities were found in 88% of patients. Some alteration of consciousness and headache occurred in most patients. Hemiparesis, hemisensory loss, and ataxia were less frequent manifestations. Vascular malformations were suspected or proved in 37% of patients, hypertension was present in 21%, and a bleeding diathesis was noted in 5%. No underlying cause was apparent in 37%. Most patients improved with supportive care only. At follow-up, 23% of patients had no neurologic deficits. In 51% of patients, minor neurologic deficits persisted, related chiefly to cranial nerves III and IV. Moderate deficits persisted in 16% of patients, and 5% of patients died. PMID- 8451724 TI - Radiation therapy for larynx carcinoma: long-term results of stage I glottic carcinoma. AB - From November 1977 through March 1982, 95 patients with early glottic carcinoma (T1N0M0) were treated with radiation therapy. Total radiation dose administered was 50 to 70 Gy over five to seven weeks period with fields of 5 x 5 cm2. Actuarial five- and ten-year survival rates were 81% and 76%, and five- and ten year relapse free survival rates were 85% and 83%, respectively. Radiation failures were surgically salvaged in 93% (14/15) and ultimate locoregional control rate was 97% (92/95). The rate of voice preservation was 86% (82/95). As a minor chronic complication polypoid lesion and impaired mobility of vocal cord was found in 9% (seven cases) and 5% (four cases) of patients without local recurrence. We need long-term follow-up after radiation therapy for the locoregional control and keeping the quality of voice. PMID- 8451725 TI - [The chemoradiotherapy of advanced colorectal carcinoma--the results and toxicity in a pilot study with 44 patients]. AB - Forty-four evaluable patients with advanced colorectal cancer were treated with simultaneous chemoradiotherapy to the small pelvis. In 34 patients locally recurrent disease and in ten patients primary tumors had been resected. 34 patients had gross and ten patients had microscopic residual tumor after surgical resection, seven of the latter with distant metastases. Radiotherapy was given to a dose of 50 Gy in five weeks. During the first two weeks of treatment simultaneous chemotherapy was applied, using continuous 24 hour intravenous infusion of 5-fluorouracil at 500 mg/m2 on days 1 to 5 and 8 to 12 and bolus injection of mitomycin C at 5 mg/m2 on days 5 and 12. Two-year local control rates in patients with microscopic residual were 76% compared to 36% in patients with gross residual disease. Two-year survival rates were 5/7 patients for microscopical residual tumor and 13/30 patients (44%) with gross residual tumor. Considerable rates of acute and late toxicity were observed, however, these rates were not higher than results reported by others. In view of the increasing interest in chemoradiotherapy for residual and recurrent colorectal cancers, a randomized multicenter study has been opened (ARO I/91). Aim of this clinical trial is to find out, whether patients with advanced colorectal cancer benefit from simultaneous chemoradiotherapy. PMID- 8451726 TI - [The transformation of a cervical chordoma into an anaplastic tumor. A case report and review of the literature]. AB - The authors describe a case of a cervical chordoma in a 28-year-old man with local recurrence and metastasis. Particular attention is paid to the fact that complete malignant transformation was observed during the follow-up. A review of the literature is undertaken chronicling the documented associations of chordoma and malignant neoplasm. Followed by a discussion of the three causes proposed to explain this phenomenon. Further on the current opinion on the therapy methods of chordomas is reviewed. PMID- 8451727 TI - Dose computation for irregular fields in cobalt-60 beam. AB - Dose computation in large irregular fields used for treating certain malignant tumors cannot be done by equivalent field methods. The present methods available for such dose computations are accurate but complicated and tedious and are amenable to only computers. This paper describes an algorithm (a semiempirical formula) of dose computation in an irregular field. Attempt is also made to estimate the dose outside the field border and in the shielded region. The dose values computed with this method at different depths in mantle and inverted Y field in a cobalt-60 beam are compared with the experimentally measured values. The method proves to be simple and accurate. The calculations can be done even manually with a calculator and a statistical table in the absence of computer facility. It also successfully estimates the dose in the shielded region and in the penumbra. PMID- 8451728 TI - [The role of radiotherapy in the treatment of desmoid tumors]. AB - Aggressive fibromatoses are benign tumors which derive from connective tissues in muscles, tendons, joints and scars. They are characterized by a low mitotic index and present without major cellular changes. The incidence is low and reaches 0.4 per 100,000. The classification in extra-abdominal, intra-abdominal and abdominal wall tumors has prognostic significance for the therapeutic decision. Extra abdominal tumors have the highest relapse rate with about two-thirds recurring even after R0 surgical resection. In this meta-analysis, 698 published cases are reviewed and analyzed with respect to the previous surgery and the therapeutic impact of postoperative radiotherapy. After an R1 surgical resection radiotherapy significantly decreases the risk for loco-regional relapse in about 40%. Radiotherapy is also recommended after an R0 surgical resection with safety margins less than 2 cm. A total radiotherapy dose of 50 Gy seems to be sufficient, whereas radiotherapy doses beyond 60 Gy provide no additional control. Following an R2 resection up to 28% of these tumors may not progress or even show a complete remission. A wait-and-see policy is justified for R1-2 resected lesions in the abdominal wall, especially if severe treatment sequelae have to be expected. The role of chemotherapy still remains questionable. PMID- 8451729 TI - [The systematics of acute and chronic radiation sequelae]. AB - A classification system in German language is proposed for scoring of acute and chronic treatment sequelae after radiotherapy. It includes all important organs and organ systems. The proposed grading corresponds to the four-scale-system of the WHO and UICC. The system is also compatible to the RTOG and EORTC acute and late radiation morbidity scoring criteria. This facilitates the data transfer for retrospective and prospective analysis of monomodal and multimodal radiotherapy treatment regimens. We recommend to use this scoring system in all German speaking countries for multicentric prospective studies. It is possible, that organ-specific sophistication of the toxicity grading will be developed in the future. These additions should conform with (inter)national standards and apply the same four-scale grading of this classification system. PMID- 8451730 TI - [Radiotherapy following a breast-preserving operation in breast carcinoma]. AB - Between 1980 and 1988, 116 patients with invasive breast cancer were treated by limited surgery with axillary node dissection followed by radiation therapy. Radiotherapy was performed by individually computerized treatment planning. The target volume dose was 50 Gy to the whole breast followed by an electron boost of 10 Gy to the tumor bed. The median follow-up period was 59 months. The actuarial overall survival rate is 93%, and the disease-free survival 75.2%. Ten (8.6%) breast recurrences occurred. Analysis of clinical and pathological prognostic factors revealed that local control was impaired by young age, negative hormone receptors, G3-4 tumors and intraductal growth. The recurrence rate for T3- and T4 tumors was 12.5%. PMID- 8451731 TI - Wax medical moulages: the Scott and White collection, 1932-1955. PMID- 8451732 TI - Henry C. McDonald, Jr, MD "the winds have welcomed you....". PMID- 8451733 TI - Budget shortfall top concern as 73rd Texas legislature opens. PMID- 8451734 TI - Ad Council campaign to promote organ and tissue donation. PMID- 8451736 TI - What a long, strange trip it's been: the history of tort reform. PMID- 8451735 TI - Legislative tort reform: "making the bird want to sing". PMID- 8451737 TI - TMA praises EPA decision on passive tobacco smoke. PMID- 8451738 TI - Refugee program sensitive to cultural, medical needs. PMID- 8451739 TI - Physicians ponder legality of private arrangements with Medicare patients. PMID- 8451740 TI - Important case addresses blood transfusions, expert witnesses, and informed consent. PMID- 8451741 TI - Managed competition comes to the fore in health-care reform debate. PMID- 8451742 TI - Outgoing president creates new CLIA microscopy category. PMID- 8451743 TI - Managed Care Check-Up to help physicians shop for best plan. PMID- 8451745 TI - Insurance companies stand to gain most from electronic claims. PMID- 8451744 TI - Medical genetics and the Human Genome Project: a historical review. AB - The $3 billion, 15-year international project to map out the nucleotide sequence of the entire human genome could revolutionize medical care in the 21st century. The location, makeup, and function of the 50,000 to 100,000 human genes could lead to tailor-made therapies not only for treating diseases but for preventing them. There may be a major role for the genetic engineer in the practice of medicine. On the other hand, the technology could identify people with undesirable genetic profiles who may be subject to discrimination by insurance companies, employers, and others. Physicians who fail to perform genetic screening may face malpractice suits for wrongful births. This article traces the historical evolution of our knowledge regarding medical genetics from the Talmud to the present day. PMID- 8451746 TI - Why not random drug screening for physicians? PMID- 8451747 TI - Future physicians may need those extra degrees. PMID- 8451748 TI - Massive hepatic necrosis in toxemia of pregnancy. AB - Hepatic rupture and infarction associated with toxemia of pregnancy usually occur in multiparous women close to 30 years of age. The most important presenting symptom is right upper-quadrant abdominal pain. Sonography is the most expedient way of making the diagnosis of either rupture or hemorrhagic necrosis, but computed tomography is more sensitive. Elevated transaminase levels and thrombocytopenia or disseminated intravascular coagulation may occur acutely but resolve quickly. Termination of pregnancy is the cornerstone of any treatment plan. Many cases may not require operative treatment other than inspection. In others, surgical hemostasis will be lifesaving. We describe four preeclamptic women, two with ruptured subcapsular hematomas and two with hemorrhagic infarction. Radiological and laboratory evidence of liver damage and recovery are presented. PMID- 8451750 TI - TSMA helps your staff help you better. PMID- 8451749 TI - Don't confuse schizophrenia with multiple personality. PMID- 8451751 TI - Was medicine's agenda attached to the wrong bill? PMID- 8451752 TI - Aggregated distributions in models for patchy populations. AB - We investigate a model describing immigration, birth, and death of parasites on a dynamic host population. The model can also be interpreted as describing a herbivore population distributed on discrete patches of vegetation. We derive differential equations for the total number of hosts/patches and the mean number of parasites/herbivores per host/patch. The equations explicitly involve the variance-to-mean ratio of the distribution. It is shown that the positive equilibrium is stable if and only if the variance-to-mean ratio as a function of the mean increases with increasing mean. Thus aggregation of the parasites alone is not sufficient to stabilize the system; it is rather the density-dependent increase in parasite mortality due to a higher aggregation at higher mean parasite loads that causes stability. From this it follows that introducing a distribution with a constant clumping parameter into the model artificially stabilizes the steady state. We derive a three-dimensional model based on an assumption about the form of the distribution of the parasites on the hosts, but without introducing additional parameters into the model. We compare stability results for this model for different types of aggregated distributions and show that the underlying distribution determines the qualitative results about the stability of the equilibrium. PMID- 8451753 TI - Induction of micronuclei and aneuploidy by the quinone-forming agents benzene and o-phenylphenol. AB - A number of carcinogens appear to exert their tumorigenic effects through the formation of quinone metabolites. These quinone-forming carcinogens are generally inactive or weakly active in standard gene mutation assays. Accumulating evidence indicates that this class of compounds may exert their genotoxic and carcinogenic effects through the induction of large-scale gene alterations. This article presents an overview of work that has been performed using recently developed molecular cytogenic techniques to investigate the aneuploidy-inducing and clastogenic properties of the major quinone-forming metabolites of benzene, a widely used industrial chemical, and o-phenylphenol, a fungicide and disinfectant. These metabolites of benzene (hydroquinone, catechol, and benzenetriol) and o-phenylphenol (phenylhydroquinone) have each been shown to be capable of interfering with chromosome segregation and inducing chromosomal breakage. These results indicate that both numerical and structural chromosomal aberrations induced by the quinone metabolites of benzene and o-phenylphenol may play a role in the carcinogenic effects of these two agents. PMID- 8451754 TI - Mitochondrial calcium release induced by prooxidants. AB - Hydrogen peroxide, a physiological metabolite, and a variety of other potentially toxic prooxidants, cause oxidation of the pyridine nucleotides NAD(P)H to NAD(P)+ in mitochondria. In Ca(2+)-loaded mitochondria NAD+ thus formed is hydrolyzed to ADP-ribose and nicotinamide. Subsequent to NAD+ hydrolysis, Ca2+ is released from the organelles via a specific pathway which is sensitive to several inhibitors, among them cyclosporine A and some of its derivatives. The release is probably regulated by peptidyl-prolyl cis-trans isomerase. Prolonged stimulation of the release pathway by certain prooxidants followed by re-uptake and release of Ca2+ (Ca2+ 'cycling') leads to collapse of the mitochondrial membrane potential, and is detrimental to the organelles. Excessive Ca2+ 'cycling' is likely to be a basis for the cell toxicity of some prooxidants. On the other hand, the toxicity of inhibitors of the prooxidant-induced Ca2+ release pathway may be due to long term Ca2+ overloading of mitochondria. PMID- 8451755 TI - Poly(ADP-ribosyl)ation, DNA strand breaks, chromatin and cancer. AB - Studies on poly(ADP-ribosyl)ation related to chromatin structure and to nuclear functions such as repair, gene expression and replication are reviewed. Poly(ADP ribosyl)ation might be involved in regulating the activity of nuclear enzymes involved in the metabolism of DNA strand breaks such as ligase II and topoisomerases I and II. In addition, it modifies nuclear proteins participating in gene expression including HMG non-histones, large T antigen, acetylated histone H4 and nuclear matrix proteins. It is speculated that poly(ADP-ribose) can induce free DNA domains by removing histones from specific nucleosomes whose DNA has been damaged. This process is proposed to require specific proteins recognizing lesions on DNA that ultimately attach the damaged site on the nuclear matrix where the repair enzymes are located. The role of poly(ADP-ribosyl)ation in carcinogenesis arises from that inhibitors of this modification potentiate the cytotoxicity of DNA-damaging drugs used in cancer chemotherapy and either enhance or inhibit tumor growth. PMID- 8451756 TI - Bioactivation of nephrotoxins and renal carcinogens by glutathione S-conjugate formation. AB - Evidence has been accumulating that several classes of compounds are converted by glutathione conjugate formation to toxic metabolites. The aim of this review is to summarize the current knowledge on the biosynthesis and toxicity of glutathione S-conjugates derived from halogenated alkenes, and hydroquinones and quinones. Different types of toxic glutathione conjugates have been identified in detail; (i) conjugates which are converted to toxic metabolites in an enzyme catalyzed multistep mechanism and (ii) conjugates which serve as a transport form for toxic quinones will be discussed. The kidney is the main, with some compounds the exclusive, target organ for compounds metabolized by these pathways. Selective toxicity to the kidney is easily explained due to the capability of the kidney to accumulate intermediates formed by processing of S-conjugates and to bioactivate these intermediates to toxic metabolites. The influences of other factors participating in the renal susceptibility and influencing human risk assessment for these compounds are discussed. PMID- 8451757 TI - Enhanced expression of the protooncogenes c-myc and c-fos in normal and malignant renal growth. AB - The protooncogenes c-myc and c-fos play an important role in growth and differentiation of renal tissue. They are highly expressed during embryogenesis in the mitotically active tubule epithelium, while in terminally differentiated tubule cells of the kidney the expression is completely shut off. Furthermore, induction of cell proliferation in cultured renal cells by addition of growth factors is preceded by enhanced expression of c-myc and c-fos. Increased expression of these protooncogenes is also obtained by treatment of kidney cells in culture with the potent nephrocarcinogen N-dimethylnitrosamine and also with the nephrotoxin and possibly nephrocarcinogen S-(1,2-dichlorovinyl)-L-cysteine. Finally, the expression of c-myc and c-fos is induced after unilateral nephrectomy during compensatory renal growth in the remaining kidney and also during regenerative cell proliferation after in vivo application of the strong nephrotoxins folic acid and mercury chloride. PMID- 8451758 TI - Generation of electronically excited triplet species at the cellular level: a potential source of genotoxicity. AB - Selected enzymatic systems can efficiently produce a product in the electronically excited triplet state. Earlier, only the formation of electronically excited singlet species was known. The formation of triplet species has been demonstrated with both normal substrates/metabolites and with xenobiotics, even at the cellular level. Triplet excited species have intrinsically much longer lifetimes than excited singlets, whereby they can be potentially important agents for normal and/or deleterious processes, including mutagenesis. Enzymically generated triplet species can damage DNA, even when protein coated, as in the case of the lambda-phage of Escherichia coli. Some evidence of damage by triplet species has also been reported for intact cells. Triplet excited species may produce their effects through type I and/or type II dark photosensitization, that is, the events may be started by H abstraction and/or singlet oxygen/superoxide ion production. The induction of lipid peroxidation, with concomitant clastogenic effects, appears to be of special importance. PMID- 8451759 TI - The structure and function of the H-ras proto-oncogene are not altered in rat liver tumors initiated by 2-acetylaminofluorene, 2-acetylaminophenanthrene and trans-4-acetylaminostilbene. AB - Liver tumors were generated in Wistar rats in an initiation-promotion experiment. 2-Acetylaminofluorene (AAF), 2-acetylaminophenanthrene (AAP), and trans-4 acetylaminostilbene (AAS) were administered to newborn animals as initiators, and phenobarbital as a promoter was added to the drinking water after weaning. Livers were examined after 26, 52, 78, and 104 weeks. Tumors were present in all groups except for at the first time point. The potency of the initiators decreased in the order AAS > AAP > AAF. DNA from tumors of all groups and of control livers was analyzed for mutations in the H-ras gene, but no mutations could be found. The sequence of almost the entire H-ras gene was determined and was compared to other H-ras genes. There are some differences with the sequence in other rat strains, particularly in intron D containing the alternative splicing site. The expression of the H-ras gene has also been studied by various methods in enzyme altered foci and tumors, but no alterations could be found. It is, therefore, concluded that structural of functional alterations of this proto-oncogene are not involved in the generation of liver tumors in Wistar rats by the three genotoxic arylamines. PMID- 8451760 TI - SEMV cell cultures: a model for studies of prostaglandin-H synthase-mediated metabolism and genotoxicity of xenobiotics. AB - Many xenobiotics and carcinogens are oxidized in vitro by prostaglandin-H synthase (PHS) in the presence of arachidonic acid or lipid peroxides. PHS has been suggested to serve as an alternative metabolic activation enzyme to the cytochrome P-450 isoenzymes, particularly in tissues low in monooxygenase activity. This article briefly describes PHS-catalyzed oxidations and reviews methods available for investigating the involvement of PHS in mediating the toxicity of certain chemicals. Since in vivo systems impose certain limitations on such studies, particular emphasis is placed on a specialized cell system which can serve as a model for investigating the PHS-dependent bioactivation of xenobiotics, its determinants and toxicological significance. This is exemplified by experiments conducted with the carcinogenic estrogen diethylstilbestrol (DES) in cell cultures derived from ram seminal vesicles which express PHS but lack monooxygenase activity. DES is oxidized by PHS in seminal vesicle (SEMV) cells and DES can induce micronuclei in this model; both processes are inhibited by indomethacin. These data support the hypothesis that PHS-dependent oxidation of DES plays a role in its genotoxicity. PMID- 8451761 TI - Oncogene activation: c-raf-1 gene mutations in experimental and naturally occurring tumors. AB - We demonstrate here consistent point mutations of the c-raf-1 proto-oncogene, within a small region of the kinase domain, in a mouse model for chemical tumor induction. This is the first demonstration of point mutated raf genes in vivo, and the first isolation of activating in vivo point mutations in the kinase domain of a proto-oncogene. The specific region where these mutations are clustered also has biological significance. This is precisely the region where 5/5 independently generated monoclonal antibodies raised against Raf-1 map to [29], and predictions based upon the crystal structure of A kinase identify this as the substrate pocket. The tumors examined show a selective specificity for Raf 1 mutations in that another family of genes, the ras proto-oncogenes which are frequently activated by point mutation in both animal and human tumors [15 21,26], is not involved. Our consistent finding of Raf-1 mutations in a mouse tumor model also has consequences for further evaluation of the role of Raf-1 in human tumor development, as it emphasizes the need to examine c-raf-1 at the sequence level. In fact preliminary screening of human lung tumors indicates point mutations at amino acid 533 (John Lyons, personal communication). Finally, the cumulative data on the critical role of Raf-1 in signal transduction and the occurrence of oncogenic Raf-1 in tumors [32-41] highlight this enzyme as an attractive target for development of novel anticancer regimens. PMID- 8451762 TI - Cell immortalization as a key, rate-limiting event in malignant transformation: approaches toward a molecular genetic analysis. AB - Recent advances using somatic cell genetic approaches have provided a convincing body of evidence that the senescence of mammalian cells in culture is controlled by a small group of genes, one or more of which are functionally deleted in the process of immortalization. Microcell-mediated mono-chromosomal transfer methods should permit precise mapping of these genes to specific chromosomal regions. Cloning of senescence genes, using either conventional 'positional cloning' techniques or retroviral insertion mutagenesis, is now a realistic possibility. The leap in our understanding of the molecular genetic events driving the alternative cellular states of limited proliferative capacity and immortality, which such advances should precipitate, will finally permit the question of the role of cell immortalization in cancer to be addressed, and may open the door to the design of new modes of cancer therapy. In addition, the precise mechanism underlying the wide difference in transformability between human and rodent cells, which should also emerge from these investigations, is likely to make a significant contribution towards resolving the key issue of the relevance of rodent tumour induction assays in assessing the potential carcinogenicity of environmental chemicals. PMID- 8451763 TI - Pathogenesis and early lesions in extranodal lymphoma. AB - Extranodal lymphomas that arise in tissues normally devoid of lymphoid tissue provide a unique opportunity for the study of the pathogenesis of lymphoma without the distraction of surrounding lymphoid tissue. This applies particularly to mucosa-associated lymphoid tissue (MALT) B-cell lymphomas, so named because they recapitulate the structure of normal MALT rather than that of lymph nodes. Before these lymphomas develop, MALT accumulates, usually in response to autoimmune injury associated with chronic gastritis caused by Helicobacter pylori, Sjogren's syndrome, Hashimoto's thyroiditis or other as yet uncharacterized disorders. The factors that induce MALT in these tissues and the point at which a clonal population of B cells arises are currently under investigation. Other extranodal lymphomas that arise in a setting of long prodromata include enteropathy associated T-cell lymphoma (EATL) which occurs in some patients with coeliac disease and lymphomas associated with immunodeficiency that appear to be caused, at least in part, by the Epstein-Barr virus. Application of new, particularly molecular genetic, techniques to the study of these extranodal lymphomas should also provide insight into the aetiopathogenesis of the more common nodal lymphomas. PMID- 8451764 TI - Human genetic instability syndromes: single gene defects with increased risk of cancer. AB - The experimental findings of the last 5 years are reviewed for the genetic instability syndromes: Xeroderma pigmentosum, Fanconi's anaemia, Ataxia telangiectasia and Bloom's syndrome. In these autosomal recessive genetic diseases, single gene defects lead to genetic instability, increased mutation rates and cancer. Deficiencies in the ability to effectively repair DNA lesions have been suggested for all of these syndromes. The status of characterization of these DNA repair defects is presented and the possible mechanisms of lesion fixation as mutation are discussed. The four known human genes whose mutation leads to inherited genetic instability are described. PMID- 8451765 TI - Cytogenetic changes in primary, immortalized and malignant mammalian cells. AB - Some chromosomes in transformed rat cells and somatic cell hybrids fail to display the presence of kinetochore proteins as detected by antikinetochore antibodies. Such chromosomes (K- chromosomes) may constitute a novel mechanism for the genesis of aneuploidy. We have analyzed primary, immortalized and malignant mammalian cells for the presence of kinetochore proteins and micronuclei. Our results suggest a correlation of the K- chromosome and micronucleus frequency with the variability in chromosome number. Upon in situ hybridization with the minor satellite and alpha satellite sequences some K- chromosomes showed a signal. This indicates that the observed lack of kinetochores is not necessarily due to a lack of centromeric DNA. We conclude that dislocated K- chromosomes may become incorporated into micronuclei which are prone to loss. Such events would be associated with the generation of aneuploidy. PMID- 8451766 TI - The relationship between the chemical structures and mutagenic specificities of the DNA lesions formed by chemical and physical mutagens. AB - The mutagenic activities of radiation, alkylating agents, and aromatic amines and amides are examined from the perspective of relating the observed patterns of mutagenesis with the structures of the premutagenic DNA lesions. The general approach taken to establish such relationships has involved the construction of viral or plasmid genomes containing specific DNA adducts. The in vivo replication of such site-specifically modified genomes results in the induction of mutations, which are characterized by DNA sequencing. It is found that the mutation types that arise in these simple systems often match those occurring in tumors produced in mammals exposed intentionally or unintentionally to carcinogenic agents. PMID- 8451767 TI - Chemistry of drug-induced DNA lesions. AB - Recent results on the action mechanisms of naturally occurring DNA-damaging antitumor antibiotics have been described. These antibiotics include neocarzinostatin (NCS) and DNA alkylating, duocarmycin A and kapurimycin A3. A series of duplex hexanucleotides of modified bases were prepared and their selectivity for C5' and C4' oxidation in the NCS-mediated degradation was investigated. Based on the cleavage data, a new binding model that permits competitive hydrogen abstraction from C5' and C4' of the DNA deoxyribose moiety has been described. Chemistry of alkylation of self complementary octanucleotide d(CGTATACG)2 by antitumor antibiotic duocarmycin A was described. It was demonstrated that N3 of adenine6 attacks the cyclopropane subunit of duocarmycin A to produce the covalently alkylated adduct. In contrast, antibiotic kapurimycin A3 alkylate N7 of guanine4 of d(CGCG)2 to provide the corresponding covalent adduct. Heating at 90 degrees C degraded the adduct to kapurimycin A3-guanine adduct and the respective abasic site-containing oligonucleotide. The structures of heat-induced abasic sites were unambiguously characterized. PMID- 8451768 TI - In-vivo assessment of DNA ligation efficiency and fidelity in cells from patients with Fanconi's anemia and other cancer-prone hereditary disorders. AB - We developed a host cell DNA ligation assay, in which we transfected linearized plasmid pZ189 into human lymphoblasts or fibroblasts in order to assess the efficiency and accuracy of DNA ligation within these host cells. We used cell lines from patients with Fanconi's anemia and other chromosome breakage or instability syndromes (Bloom's syndrome, ataxia telangiectasia, Werner's syndrome). With the Fanconi's anemia lymphoblast line GM8010 we did not find a reduced, but a slightly hypermutable DNA ligation. Mutation analysis revealed a unique 7.9-12.5-fold increase in insertions or complex mutations. With cells from the other chromosome breakage/instability syndromes we also found a hypermutable and/or reduced DNA ligation. An impaired DNA ligation might be a common molecular mechanism of genetic instability in these disorders. PMID- 8451769 TI - Normal and reverse dose-rate effect for the induction of mutants in somatic cells by ionizing radiation. AB - In radiobiology the reduction of the dose-rate in general diminishes the degree of the biological effect per unit dose. This phenomenon is characterized by the dose-rate effectiveness factor (DREF). DREF is the factor by which a risk per unit dose obtained from data at high dose and high dose-rate overestimates the risk at low doses and/or low dose-rates. In general, DREF is in the range of 2 to 10. In the first part of this review, a short survey of the modern microdosimetric approach for a better understanding of radiation load on the cellular level and the significance of dose-rate is given. Experiments on the influence of dose-rate on the mutagenicity of ionizing radiation in cultured cells are reviewed. In contrast to other biological effects, in most experiments the reduction of the dose-rate had no or even a reverse dose-rate effect (DREF < or = 1). In the second part results on the influence of dose-rates on the induction of HGPRT-deficient T-lymphocytes in mice irradiated in vivo are given. Mutagenicity decreases with dose-rate and DREF values between 3-10 were measured. Possible reasons for the discrepancy between in vitro and in vivo experiments are discussed. PMID- 8451770 TI - Genotoxicity studies of benzofuran dioxetanes and epoxides with isolated DNA, bacteria and mammalian cells. AB - 1,2-Dioxetanes, very reactive and high energy molecules, are involved as labile intermediates in dioxygenase-activated aerobic metabolism and in physiological processes. Various toxicological tests reveal that dioxetanes are indeed genotoxic. In supercoiled DNA of bacteriophage PM2 they induce endonuclease sensitive sites, most of them are FPG protein-sensitive base modifications (8 hydroxyguanine, formamidopyrimidines). Pyrimidine dimers and sites of base loss (AP sites) which were probed by UV endonuclease and exonuclease III are minor lesions in this system. While the alkyl-substituted dioxetanes do not show any significant mutagenic activity in different Salmonella typhimurium strains, heteroarene dioxetranes such any significant mutagenic activity in different Salmonella typhimurium strains, heteroarene dioxetanes such as benzofuran and furocoumarin dioxetanes are strongly mutagenic in S. typhimurium strain TA100. DNA adducts formed with an intermediary alkylating agent appear to be responsible for the mutagenic activity of benzofuran dioxetane. We assume that the benzofuran epoxides, generated in situ from benzofuran dioxetanes by deoxygenation are the ultimate mutagens of the latter, since benzofuran epoxides are highly mutagenic in the S. typhimurium strain TA100 and they form DNA adducts, as detected by the 32P-postlabelling technique. Our results imply that the type of DNA damage promoted by dioxetanes is dependent on the structural feature of dioxetanes. Furthermore, the direct photochemical DNA damage by energy transfer, i.e., pyrimidine dimers, plays a minor role in the genotoxicity of dioxetanes. Instead, photooxidation dominates in isolated DNA, while radical damage and alkylation prevail in the cellular system. PMID- 8451771 TI - Reactivity and genotoxicity of arylnitrenium ions in bacterial and mammalian cells. AB - Electrophilic arylnitrenium ions are considered to be the ultimate reactive intermediates formed by metabolism of mutagenic and carcinogenic arylamines and nitroarenes; they can produce DNA damage by reaction with specific sites on DNA bases. We studied their formation, reactivity and the genotoxic sequelae of their reactions with cellular DNA to understand the mutagenic and carcinogenic activities of arylamines and nitroarenes as a function of their chemical structure. Arylnitrenium ions were generated by the convenient non-metabolic procedure, photolysis of arylazides, to study the reactivity of these ultimate intermediates with DNA, by means of 32P-postlabelling, and the induction of histidine reversions in Salmonella, HPRT mutations and sister chromatid exchange in mammalian (Chinese hamster V79) cells. Good correlations were observed between the DNA-binding potencies and the mutagenic and SCE-inducing potencies of the arylnitrenium ions, among these the nitrenium ions derived from the heterocyclic food mutagens/carcinogens MeIQ, IQ, and MeIQx. This suggests that the reactivity of the arylnitrenium ions and the quantity of adducts formed with DNA are the principal determinants of the final quantity of genetic alterations in Salmonella and in V79 cells. Conversely, the quality of the adducts, that is, the structure of the arylamine residue bound, appears to be of less significance. PMID- 8451772 TI - The possible role of alpha, beta-unsaturated carbonyl compounds in mutagenesis and carcinogenesis. AB - alpha, beta-Unsaturated carbonyl compounds are industrially important compounds, ubiquitous in the environment and are formed endogenously. They interact with proteins and enzymes. Genotoxicity was found in eucaryotic cells and some compounds were carcinogenic. Unsaturated carbonyl compounds are considered to play an important role in human cancer. Insufficient and contradictory results were reported on mutagenicity. We demonstrated a clear mutagenic potential for these compounds and have shown interference of their bacterial toxicity with an adequate testing. Structure-mutagenicity relationships were confirmed by the results of the SOS-chromotest. The compounds induce DNA-strand breaks. However, we did not find indications for cross linking. With mutagenic alpha, beta unsaturated carbonyl compounds we isolated and characterized 1,N2-cyclic deoxyguanosine adducts, 7,8-cyclic and 7-linear guanine adducts as well as 1,N2 7,8-biscyclic adducts and 1,N2-cyclic, 7-linear bisadducts. Reactivity of these compounds towards nucleosides runs in parallel with their mutagenic potential. Mutagenic and carcinogenic activities most probably depend on these reactions with DNA, and DNA adducts can be utilized as indicators for the role of these compounds in human carcinogenicity. PMID- 8451773 TI - The 10,11-epoxide-10,11-diol pathway of carbamazepine in early pregnancy in maternal serum, urine, and amniotic fluid: effect of dose, comedication, and relation to outcome of pregnancy. AB - Epoxide metabolites of carbamazepine (CBZ) have been suggested to play a role in the occurrence of congenital malformations observed in infants exposed to CBZ. We have investigated the 10,11-epoxide-10,11-diol pathway of CBZ in pregnant epileptic patients receiving CBZ alone or in combination with other antiepileptic drugs in relation to the outcome of pregnancy in a prospective manner. The women were referred to our clinic before 16 weeks of gestation for prenatal diagnosis of fetal malformations, including neural tube defects, by ultrasound and amniocentesis. The availability of amniotic fluid samples enabled us to determine to what extent CBZ and its main metabolites reached the amniotic fluid. In 100 pregnancies with first trimester CBZ exposure (including 7 with malformed outcome), parent drug and metabolite concentrations in maternal serum were evaluated. CBZ-10,11-epoxide concentrations increased with increasing dose. Comedication with phenobarbital led to lower 10,11-epoxide concentrations in maternal serum and a higher percentage of the dose recovered in urine as 10,11 diol. Valproate comedication led to slightly higher 10,11-epoxide concentrations in maternal serum, in combination with lower CBZ concentrations and a lower percentage of the dose recovered in the urine as 10,11-diol. In amniotic fluid, concentrations of CBZ and its main metabolites in most patients were 2 to 2.5 times higher than the free concentrations in maternal serum. Metabolites and parent drug concentrations in amniotic fluid correlated with their free concentration in maternal serum, but stronger with each other in amniotic fluid. No significant differences in levels of CBZ and its metabolites were observed between pregnancies with normal and malformed outcome. PMID- 8451774 TI - Pharmacokinetics of citalopram in relation to the sparteine and the mephenytoin oxidation polymorphisms. AB - The relationship between the metabolism of the selective serotonin reuptake inhibitor citalopram and the sparteine and mephenytoin oxidation polymorphisms was studied in 24 healthy male volunteers, constituting panels of extensive metabolizers of sparteine and mephenytoin (n = 10), poor metabolizers of sparteine (n = 8), and poor metabolizers of mephenytoin (n = 6). Each subject was given 40 mg/day citalopram for 10 days and citalopram, and its des- and didesmethylmetabolites were assayed in serum and urine. Using a nonenantioselective analytical method (high-performance liquid chromatography), it was shown that the citalopram elimination partially depends on the mephenytoin oxygenase, since steady-state serum concentration, half-life, and area under the serum concentration/time curve for citalopram were significantly higher in poor metabolizers of mephenytoin than in extensive metabolizers of mephenytoin. Both citalopram total clearance and demethylation clearance (formation of desmethylcitalopram) were significantly lower in poor metabolizers of mephenytoin compared to extensive metabolizers (median 15.2 vs. 27.3 and 2.6 vs. 5.9 L/h, respectively). It was further indicated that the demethylation of desmethylcitalopram to didesmethylcitalopram depends on the sparteine oxygenase CYP2D6. Didesmethylcitalopram could virtually not be detected in any poor metabolizers of sparteine, contrasting measurable serum levels in all sparteine/mephenytoin extensive metabolizers. The demethylation clearance of desmethylcitalopram was significantly lower in sparteine poor metabolizers compared to extensive metabolizers (0.3 vs. 2.4 L/h, respectively). During administration of citalopram, there was a modest increase in sparteine metabolic ratio from median 0.31 to 0.80 in extensive metabolizers of sparteine, whereas the mephenytoin S/R ratio was unaltered during citalopram treatment. Both the sparteine and the mephenytoin oxidation polymorphism thus appear to contribute partially to the total pharmacokinetic variability of citalopram. PMID- 8451775 TI - Citalopram: interaction studies with levomepromazine, imipramine, and lithium. AB - The pharmacokinetic interactions between the selective serotonin reuptake inhibitor citalopram, given as an oral dose of 40 mg/day for 10 days, and (1) levomepromazine (50 mg single oral dose), (2) imipramine (100 mg single oral dose), and (3) lithium (30 mmol/day orally for 5 days) were examined in three panels each of 8 healthy young male volunteers (age 20-31). All volunteers were classified as extensive metabolizers of sparteine and mephenytoin. Each subject completed three study phases--one with citalopram alone, one with one of the three other drugs, alone, and one with citalopram combined with the corresponding other drug. For citalopram and its metabolites, a non-enantioselective analytical method (high-performance liquid chromatography) was used. Only two statistically significant interactions were indicated. First, levomepromazine caused a 10-20% increase from the initial steady-state levels of the primary citalopram metabolite, desmethylcitalopram. Second, citalopram caused approximately 50% increase in the single-dose area under the serum concentration/time curve of desipramine (primary metabolite or imipramine) and a corresponding reduction in the level of the subsequently formed metabolite 2-hydroxydesipramine. These findings are in agreement with the recent observations that (1) the demethylation of desmethylcitalopram (to didesmethylcytalopram) is partly mediated via the sparteine/debrisoquine oxygenase (CYP2D6) and that levomepromazine is a potent inhibitor of CYP2D6, and (2) that desmethylcitalopram has a somewhat stronger affinity for CYP2D6 than desipramine, and therefore may inhibit the hydroxylation of desipramine, which is also a substrate of CYP2D6. PMID- 8451776 TI - A sensitive high-performance liquid chromatographic method for the determination of 6-mercaptopurine in plasma using precolumn derivatization and fluorescence detection. AB - A sensitive high-performance liquid chromatographic (HPLC) method for measuring plasma concentrations of 6-mercaptopurine (6-MP) is described. After protein precipitation with 5-sulfosalicylic acid, samples are subjected to precolumn derivatization using the thiol-reactive fluorophore monobromobimane (mBrB). The drug-mBrB adduct is then resolved by isocratic elution from a C18 reversed-phase support and quantified by fluorescence detection. Recovery of 6-MP after protein precipitation was consistently > 85% and the drug-mBrB adduct was found to be stable for at least 2 weeks at room temperature. With plasma samples containing 30 nM 6-MP, the assay displayed within-run (n = 6) and between-day (n = 6) coefficients of variation of 2.2 and 10.6%, respectively. The limit of detection for 6-MP in plasma was 3 nM (500 pg/ml) and the standard curve was linear up to 3 microM. Using this method, we have observed that 6-MP is stable in heparinized whole blood for at least 24 h provided samples are maintained on ice. Since this method requires few manipulations during sample preparation and is readily adaptable to automated techniques, it may prove useful in the routine clinical laboratory setting. PMID- 8451777 TI - Free phenytoin monitoring in serum and saliva of epileptic patients in China. AB - Twenty-three serum samples and 13 saliva samples from 14 Chinese epileptic patients treated with phenytoin (DPH) were obtained to study the correlations between total, free serum, and saliva DPH concentrations. The binding of DPH to serum protein was assessed by equilibrium dialysis, and total and free DPH concentrations were analyzed with a domestic fluorescence polarization immunoassay reagent by the TDx system. A strong correlation existed between the total and free concentrations (r = 0.90, n = 20, p < 0.001). The mean value for the DPH free fraction was 11.13 +/- 3.65%. The mean value for the saliva fraction was 9.40 +/- 2.60%. This is the first attempt to monitor free DPH concentrations in serum in Chinese patients. PMID- 8451778 TI - A method for rapid determination of lorazepam by high-performance liquid chromatography. AB - A new sensitive method using solid-phase column extraction and high-performance liquid chromatography (HPLC) has been developed for the determination of lorazepam and its glucuronide metabolite in human plasma. Extraction was performed with a C2-Bond Elut column followed by reverse-phase HPLC of the sample. The detection limit of lorazepam in plasma was 0.5 micrograms/L. Standard curves over the concentration range from 2.5 to 75 micrograms/L had good linearity. Intra-assay variability ranged from 2.0 to 6.2% and interassay variability from 4.8 to 8% at the concentration range of 5-50 micrograms/L. PMID- 8451779 TI - Influence of single and repeated doses of oxcarbazepine on the pharmacokinetic profile of felodipine. AB - Eight healthy male volunteers (age 25-41 years) entered an open-label, within subject study. They were treated for 13 consecutive days with felodipine (FEL) extended-release tablets, 10 mg daily. On day 6, oxcarbazepine (OXC) 600 mg was given in the morning, and from day 7 to 13, the daily dose was increased to 450 mg b.i.d. Blood samples for measurement of FEL and its pyridine metabolite (determined by gas-chromatography) were drawn just before dosing and at 2, 4, 6, 8, 10, 12, and 24 h after dosing on days 5, 6, and 13. Steady-state pharmacokinetic parameters of FEL and its pyridine metabolite were not influenced by the single dose of OXC. Repeated coadministration of OXC significantly reduced the area under the concentration-time curve (AUC0-24) of FEL by 28% and the FEL maximum plasma concentration (Cmax) by 34%. This reduction in FEL bioavailability is much smaller than that observed after co-administration of carbamazepine (CBZ) (i.e., 94%). PMID- 8451780 TI - Lack of pharmacokinetic interaction between chloroquine and imipramine. AB - The pharmacokinetic interaction between chloroquine (CQ) and imipramine was investigated in six healthy volunteers who received 300 mg of CQ, 50 mg of imipramine, and combined doses of both drugs in a randomized, crossover design. Blood and urine samples were collected at predetermined time intervals and were analyzed for the drugs and their metabolites by high-performance liquid chromatography methods. The results revealed that the plasma concentrations of CQ and its pharmacokinetic parameters were not significantly altered when CQ was coadministered with imipramine (p > 0.1). The plasma concentration-time profiles and the disposition characteristics of imipramine also were not altered after coadministration with CQ. The results suggest that there appears to be no pharmacokinetic interaction between CQ and imipramine given as single oral doses. PMID- 8451781 TI - Determination of a gentamicin loading dose in neonates and infants. AB - The use of gentamicin as a co-therapy for the treatment of sepsis is common practice in neonates and infants. Gentamicin dosing guidelines have been developed over the past 20 years to accommodate a slower renal elimination rate of gentamicin in the neonatal population. Recently, it has become evident that early attainment of serum gentamicin concentrations > or = 5 micrograms/ml results in a greater therapeutic outcome in septic adult patients. As neonatal immunity is immature and aminoglycosides have an extended elimination half-life in the very young population, reassessment of the initial gentamicin dose has become necessary. Using retrospective data, we determined the amount of gentamicin necessary to effectively "load" a group of neonatal/pediatric patients to achieve initial serum concentrations of 6 or 8 micrograms/ml. One hundred sixty-six patients less than 12 months postnatal age were studied. The mean initial dose delivered was 2.41 mg/kg. Younger patients demonstrated larger gentamicin apparent volumes of distribution and slower elimination half-lives than did older patients. Initial serum gentamicin concentrations calculated from steady-state pharmacokinetic parameters were significantly lower than those seen at steady state. In order to achieve initial serum gentamicin concentrations > 6 micrograms/ml an initial dose of 3 mg/kg would be necessary in the group of patients studied. Younger patients (< or = 34 weeks gestational age) would likely require 4 mg/kg as an initial dose. PMID- 8451782 TI - Validation of tobramycin monitoring in adolescent and adult patients with cystic fibrosis. AB - The predictive performance of a dosage calculation method for the optimization of tobramycin therapy was studied retrospectively in 29 patients with cystic fibrosis. The dosage calculation method was based on a linear one-compartment open model. It used peak and trough serum concentrations of the aminoglycoside. Bias in the peak concentration was 0.20 mg/L and precision was 1.2 mg/L. Bias in the trough concentration was -0.06 mg/L and precision was 0.33 mg/L. The results were clinically satisfactory. Comparison with previously published results of the predictive performance of other dosage calculation methods showed that the method studied was at least as good. PMID- 8451783 TI - Pharmacokinetics of cyclosporine A after intravenous and oral administration in liver transplant patients measured with high-performance liquid chromatography. AB - Cyclosporine A (CsA) bioavailability after i.v. and oral administration was studied in six stable liver transplant patients with open and clamped bile drain. CsA levels were determined by the high-performance liquid chromatography method (HPLC). External bile drainage decreased CsA absorption considerably. Clamping the bile drain resulted in higher and earlier peak CsA levels. Clamping the bile drain increased the bioavailability (9.6% vs. 7%, p < 0.05), but even then it was considerably lower than the value of approximately 30% generally reported in literature. It is recommended to continue i.v. CsA administration to obtain therapeutic plasma concentrations. Early bile drain clamping or bile refeeding will improve CsA absorption and may also result in continuously therapeutic CsA levels. PMID- 8451784 TI - A reliable high-performance liquid chromatography assay for high-throughput routine cyclosporin A monitoring in whole blood. AB - We report here a reliable high-performance liquid chromatography-ultraviolet assay for routine assay of cyclosporin A (CsA) in whole blood using solid-phase extraction. This assay is linear, between 20 and 2,000 micrograms/L, with correlation coefficients > 0.998 for five consecutive standard curves. All coefficients of variation (CV) were < 8% at CsA concentrations of 45, 480, and 1,800 micrograms/L, with the exception of the between-day CV at 45 micrograms/L, which was < 15%. The relative accuracy of the method is > 94% at 45, 480, and 1,800 micrograms/L. The mean recoveries for CsA and cyclosporin D (internal standard) were 38.2 +/- 4.8% (n = 45) and 40.1 +/- 6.7% (n = 45), respectively. This method has proven to be reliable and robust in a high-throughput therapeutic drug monitoring laboratory. PMID- 8451785 TI - [Neurological complications of herpes zoster in the central nervous system]. AB - The Varicella zoster virus may affect the central nervous system (CNS) as a complication of herpes zoster (HZ). A series of neurological syndromes are described and, on the basis of a review of the literature and two illustrative case histories, the symptomatology, pathogenesis, therapeutic possibilities and the diagnostic difficulties in HZ-associated cerebral vasculitis and HZ associated encephalitis are reviewed. Progressive multifocal encephalopathy in immune-insufficient individuals is briefly mentioned. The diagnosis is most frequently established on the basis of the clinical picture when the characteristic symptoms develop in connection with cutaneous HZ. A long latent period may result in defective recognition of the connection. Immuno-suppression and dissemination are critical determinants for the course of the condition but, in immune-competent individuals, the morbidity and mortality are low. Treatment with acyclovir is employed to an increasing extent with good results but the conditions are rare and clinically controlled investigations are not available. It is important that the possibility of HZ-associated CNS-disease is borne in mind, in view of the therapeutic possibilities. The pathogeneses of these complications is little understood but there is increasing evidence that a direct viral invasion is the mechanism responsible. A post-infectious immune-mediate mechanism is also another popular opinion. PMID- 8451786 TI - [Occurrence of Helicobacter pylori and gastritis among healthy persons without gastrointestinal symptoms]. PMID- 8451787 TI - [Ankle alloplasty. 3-7,5-year follow-up]. PMID- 8451788 TI - [Osteosuturing with the Mitek anchor system--experiences from the first 17 operations]. AB - In September 1990, the Mitek Anchor System was introduced commercially in Denmark. Since the introduction of the system in our department in October 1991 and until June 1992, we have collected data consecutively from all operations, in which the anchors have been used. The registration has included pre-operative history, type of operation and findings per- and post-operatively. In the above mentioned period, Mitek anchors have been used in seventeen operations: Twelve Bankart-repairs, three fractures of the major tubercle of the humerus, one reattachment of the ulnar collateral ligament of the thumb and one reattachment of the medial collateral ligament of the knee. None of the patients operated for Bankart lesions have had redislocations, and none of the anchors were displaced on X-rays. The three fractures of the major tubercle of the humerus have all remained without dislocation after fixation. No side-instability was found in the operated thumb, and the operated knee was making progress in training. By presenting the patient-data and the temporary post-operative results we conclude, that the anchors seem highly usable not only in Bankart-operations. Follow-up will be continued. PMID- 8451790 TI - [Compulsory procedures in the psychiatric department, Frederiksberg Hospital, before and after introduction of the new psychiatric legislation]. AB - Registration of compulsory procedures in a psychiatric department before and after the reform of the Danish law concerning commitment and compulsory procedures in psychiatry. The purpose of this investigation was to register if the law reform 01.10.1989 caused changes in the extent of compulsory procedures in a psychiatric department. The study was prospective. During the period: 01.02.1988-30.09.1991, all compulsory procedures in the department of psychiatry, Frederiksberg Hospital, were registered. A total of 289 patients had been subjected to compulsory procedures during 336 admissions. The compulsory procedures registered were: incarceration in the department, forced medication and restraint by a belt. The total number of admissions with compulsory procedures increased after the law reform. The number of incarcerations increased. No changes were registered in the number of restraints and forced medications in connection with the law reform but, two years after, increases of 37% and 74% respectively were registered. One of the main purposes of the law reform was to limit and, if possible, to prevent compulsory procedures. This purpose has not been fulfilled. The increase in the extent of compulsory procedures in the latter part of the observation period is probably caused by factors such as increase bed occupancy and decrease in resources. PMID- 8451789 TI - [Merkel cell carcinoma]. AB - Eight patients with Merkel cell carcinoma are reported to document their response to surgery and/or radiotherapy. Four patients who initially underwent surgery without postoperative radiation therapy all had local recurrence. Two patients were treated with postoperative radiation therapy and two were treated with radiation therapy without excision of the tumour. None of these four patients had local recurrence. Five patients developed regional recurrence. Recurrence was seen in one patient in the irradiated field. Metastatic disease was not seen in any case. These results combined with a review of the literature suggest that radiation therapy postoperatively to both the surgical bed and the draining lymph nodes may improve local regional tumour control. PMID- 8451791 TI - [IGG index or oligoclonal bands in the diagnosis of disseminated sclerosis]. AB - Intrathecal synthesis of IgG was measured in 136 patients using agarose isoelectric focusing followed by immunoperoxidase staining for the detection of oligoclonal bands, and separate measurement of the IgG-index by immune electrophoresis. Oligoclonal bands were detected in 10/52 patients with other neurological diseases (OND). Five of these patients had possible multiple sclerosis (MS), and five had infections of the central nervous system. Oligoclonal bands were detected significantly more often in patients with clinically definite MS (24/26 patients (92%): p < 10(-9)) and in patients with acute optic neuritis, which is often an early manifestation of MS (34/58 patients (56%): p = 0.00005). An elevated IgG-index was detected in 15/25 MS-patients (60%), and in 13/56 patients with optic neuritis (20%). We conclude that isoelectric focusing is a valuable method for the detection of intrathecal production of IgG, and, especially in optic neuritis, has a higher sensitivity than the IgG-index. The method is recommended in the routine diagnosis of MS. PMID- 8451792 TI - [Blood pressure and mortality--10-year follow-up of the Osterbro study]. PMID- 8451793 TI - [Herpes genitalis in pregnancy]. PMID- 8451794 TI - [Verrucous carcinoma of a prolapsed uterus]. AB - A case of verrucous carcinoma on the uterine cervix is presented. Verrucous carcinoma is a rare variant of epidermoid carcinoma, characterized by local invasive growth and rare lymphogenic spread. Treatment consists of simple hysterectomy. PMID- 8451795 TI - [Treatment of unknown primary tumor with cytostatic agents]. PMID- 8451796 TI - [Technical extension of multiple choice tests]. PMID- 8451797 TI - [Problems of cause-explanations in medical statistics]. PMID- 8451798 TI - [What is the price of raw morphine?]. PMID- 8451800 TI - Levy board outlines the fruits of its research. PMID- 8451799 TI - [Fluoxetine]. PMID- 8451801 TI - Pathological lesions associated with Anoplocephala perfoliata at the ileo-caecal junction of horses. AB - The intestinal tracts of 20 horses, killed at a local abattoir and of unknown age, sex and previous clinical history were examined for the presence of Anoplocephala perfoliata attached to the ileo-caecal junction. Four horses had no tape-worms, nine had one to 20 tapeworms attached to the mucosa and seven had more than 100 attached to the mucosa. The histological changes of thickening, ulceration and eosinophil infiltration of the mucosa at the ileo-caecal junction were more severe when more than 100 parasites were present. PMID- 8451802 TI - An application of sinography in small animal practice. AB - Sinography is a well recognised aid to clinical diagnosis in human medicine; it is used in equine practice but is less commonly used in small animal practice. The technique was used to investigate four dogs with sinuses associated with radiolucent foreign bodies secondary to penetration wounds. PMID- 8451803 TI - Yield of embryos in PMSG-superovulated cows treated with anti-PMSG six or 18 hours after the peak of luteinising hormone. AB - One hundred and forty-six Dutch cross Friesian cows were selected from a local slaughterhouse and synchronised with norgestomet. The 134 cows with a normal progesterone pattern after the removal of the norgestomet implant were treated intramuscularly with 3000 iu pregnant mare's serum gonadotrophin (PMSG) on day 10 followed by 22.5 mg prostaglandin 48 hours later. Blood samples were collected daily and at hourly intervals from 30 to 54 hours after the prostaglandin. The 113 cows with a pre-ovulatory peak of luteinising hormone (LH) were divided into three groups: 37 control cows (group 1) received a placebo six hours after the LH peak; 42 cows (group 2) received anti-PMSG six hours after the LH peak and 34 cows (group 3) received anti-PMSG 18 hours after the LH peak. All the cows were inseminated 10 hours after the LH peak. Six or seven days after insemination the cows were slaughtered and the embryos were evaluated after flushing the ovaries, and the numbers of corpora lutea, cysts and follicles on the donor ovaries were counted. Treatment with anti-PMSG had no significant effect on the numbers of corpora lutea or the numbers of embryos compared with the control group. The mean (+/- sem) numbers of corpora lutea were 14.7 +/- 1.4, 16.3 +/- 1.4 and 16.6 +/- 1.4 for groups 1, 2 and 3, respectively. The numbers of transferable embryos were 3.5 +/- 0.6, 4.1 +/- 0.7 and 5.0 +/- 0.7 for groups 1, 2 and 3, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8451804 TI - Incisional swelling following celiotomy in cats. PMID- 8451805 TI - Equine motor neuron disease. PMID- 8451806 TI - Dermatitis nephropathy syndrome of pigs. PMID- 8451807 TI - Incontinence in giant schnauzers. PMID- 8451808 TI - Bovine embryo transfer certification. PMID- 8451809 TI - Chronic superficial keratitis. PMID- 8451810 TI - Ovine iritis. PMID- 8451811 TI - Detection of bacterial antigens in milk samples from clinical cases of bovine mastitis in which culture is negative. AB - ELISAs to detect antigens against Staphylococcus aureus, Escherichia coli, Streptococcus agalactiae, Streptococcus dysgalactiae and Streptococcus uberis were developed and used on whey samples from quarter milk samples from cases of clinical mastitis in which no bacterial pathogen had been isolated by standard culture techniques. Antigens against one or other of the bacteria listed above were detected in 68 per cent of 84 samples. Fifty-one per cent of the 84 samples contained antigens to E coli. Antigens against one or other of these bacteria were also detected in 51 per cent of 53 quarter milk samples which were negative on culture but had somatic cell counts of more than 500,000 cells/ml. It is suggested that ELISAs for the detection of antigens in quarter milk samples could be a useful adjunct to culture, to determine the infection status of a quarter. PMID- 8451812 TI - Evaluation of a standardised questionnaire for the detection of dysphagia in 69 dogs. AB - The diagnosis of dysphagia in the dog requires an evaluation of a variety of signs that can be caused not only by a 'swallowing disorder' but also by several other pathological conditions. Most owners mention coughing, vomiting, regurgitation and nasal discharge, and the clinician must decide whether these signs are related to dysphagia. In this study a standardised questionnaire for the diagnosis and localisation of dysphagia was evaluated for its accuracy by comparing the results with contrast videofluorography as the definitive standard. The purpose of the study was to optimise the selection of dogs for more expensive diagnostic procedures such as videofluorography and electromyography. In a group of 69 dogs with 'swallowing problems' the questionnaire had a sensitivity of 0.97 and a positive predictive value of 0.94 for dysphagia in general. The questionnaire was also useful for the exclusion of oral phase dysphagia, with a specificity of 0.70 and a negative predictive value of 0.97. Most dogs with pharyngeal phase dysphagia could be detected by using the questionnaire (sensitivity 0.91). The questionnaire was not of specific value for the detection or exclusion of oesophageal phase dysphagia, for which it had a sensitivity of 0.69, a specificity of 0.57 and predictive values for positive and negative tests of 0.79 and 0.44, respectively. PMID- 8451813 TI - Paratuberculosis in farmed red deer (Cervus elaphus) in Ireland. AB - Paratuberculosis was diagnosed in one 18-month-old and two 30-month-old hinds in a herd of 70 red deer (Cervus elaphus) in Ireland. Loss of condition and intermittent diarrhoea were the main clinical findings. Clumps of acid-fast organisms were found in the faeces of the three deer. Post mortem examination of one deer showed a slight swelling and pallor of the intestinal tract and associated lymph nodes. Histopathology showed a severe, granulomatous enteritis and lymphadenitis, with extensive cellular infiltration, notably with epithelioid macrophages containing numerous acid-fast organisms. Mycobacterium paratuberculosis was isolated from intestinal and lymph node samples. Paratuberculosis was also confirmed in one of nine clinically normal, yearling stags, sampled at slaughter. Complement fixation tests and enzyme-linked immunosorbent assays gave higher readings for clinically affected deer than healthy ones. Acid soil on the farm was believed to be a contributory cause. PMID- 8451814 TI - Differentiation of abortion-inducing and intestinal strains of Chlamydia psittaci isolated from ruminants by the microimmunofluorescence test. AB - Forty-two isolates of Chlamydia psittaci from ruminants, principally from cases of abortion (21 strains) and from subclinical intestinal infections (13 strains), were serotyped by an indirect microimmunofluorescence test. The strains could be divided into the previously described serotypes 1 and 2. Strains causing abortion and intestinal strains belonged to two different serotypes: the abortion-inducing strains were mostly in serotype 1 whereas the intestinal strains were mostly in serotype 2. A close relationship was found between the serotypes and their invasiveness in mice. PMID- 8451815 TI - Problems with using weight versus carapace length relationships to assess tortoise health. PMID- 8451816 TI - Maximum residue threat. PMID- 8451817 TI - Casualty slaughter. PMID- 8451818 TI - Poultry meat inspection. PMID- 8451819 TI - Relations with meat inspectors. PMID- 8451820 TI - Diagnosis of toxoplasma abortion in sheep. PMID- 8451821 TI - Bovine disseminated haemangioma. PMID- 8451823 TI - A house-year for veterinary surgeons? PMID- 8451822 TI - Fatal bovine viral diarrhoea virus infection of adult cattle. PMID- 8451824 TI - Elevated GLDH levels in cattle. PMID- 8451825 TI - Hydrocephalus in a flock of Suffolk sheep. PMID- 8451826 TI - Professional image. PMID- 8451827 TI - Bovine petechial fever (Ondiri disease). AB - Bovine petechial fever is a Rickettsial disease of cattle, which has been diagnosed, only in Kenya, East Africa. Other countries in the region share some of the biotopes in which the disease occurs, and may well have the infection. The disease is characterised by widespread petechial and ecchymotic haemorrhages on the mucosal surfaces, and throughout the serosal and subserosal surfaces of the body organs and cavities. It may be fatal in up to 50% of untreated cases. The causal organism may be demonstrated most readily in the cytoplasm of polymorphonuclear granulocytes of the peripheral blood, as well as other leucocytes, and has been classified as Cytoecetes ondirii, a member of the tribe Ehrlichiae. Circumstantial and other evidence suggests that the disease is transmitted by an arthropod vector, which has yet to be identified. The blood of a naturally infected wild ruminant, the bushbuck, Tragelaphus scriptus has been shown to remain infective for at least 2 years, and other species such as the African buffalo, Syncercus caffer for at least 5 weeks. These and possibly other species, may serve as the amplifying and reservoir hosts. PMID- 8451828 TI - Characteristics of Escherichia coli isolated from septic foals. AB - Fifteen Escherichia coli isolates from the blood and tissue of foals with septicemia were compared with 15 from the feces of clinically normal horses. Comparisons were made with respect to survival in normal equine serum, production of aerobactin, and production of hemolysin. Isolates from the blood and tissues of septic foals were more likely to be resistant to equine serum than were isolates from feces of clinically normal horses. There were minimal differences between the isolates with respect to aerobactin and hemolysin production, almost all being nonhemolytic and aerobactin negative. Serum resistance is probably a virulence determinant for invasive E. coli in horses. PMID- 8451829 TI - Blocking enzyme-linked immunosorbent assay for detection of antibodies against Actinobacillus pleuropneumoniae serotype 8. AB - A blocking enzyme-linked immunosorbent assay (ELISA) for detection of antibodies against Actinobacillus pleuropneumoniae serotype 8 is described. The test is based upon a competitive reaction between the serum to be tested and a polyclonal rabbit antiserum prepared against serotype 8 and absorbed with whole cells of serotypes 3 and 6. The blocking ELISA proved able to distinguish animals infected with serotype 8 from those infected with any other serotype of A. pleuropneumoniae including the antigenically closely related serotypes 3 and 6. Positive results were not observed with field sera from serotype 6 infected herds or from herds known to be free from A. pleuropneumoniae infection. PMID- 8451831 TI - Seroepidemiology of mycoplasmal pneumonia of swine in Japan as surveyed by an enzyme-linked immunosorbent assay. AB - Antibodies to Mycoplasma hyopneumoniae were surveyed by enzyme-linked immunosorbent assay (ELISA) on serum, colostrum and milk samples collected from sows and on sera of growing/finishing pigs in Japan. Only one of 196 specific pathogen-free sows induced a low ELISA value, while 72% of 411 sows from conventional herds were seropositive. A seropositive rate in the conventional sows gradually decreased with an increase in farrowing frequency or with age. In 3267 growing/finishing pigs ranging in age from one to six months, a seropositive rate increased remarkably from the age of 4 months onwards, reaching the maximum at the age of 6 months. A survey conducted on 42 conventional farms revealed that the highest seroconversion occurred when pigs were 4 months of age. The level of maternal antibodies was proportional to that of the dam's colostral antibodies. After maternal antibodies waned, active immunity in newborn piglets from dams with high colostral antibodies appeared earlier and higher than that in piglets from dams with low colostral antibodies. In 950 slaughter pigs, there was a correlation between seropositiveness and the presence of pneumonic lesions, but the ELISA value did not correlate with the degree of the lesions. Pigs that were raised under unfavorable environmental conditions developed pneumonic lesions more frequently than pigs rearing under better conditions, regardless of their immune status. These results suggested that M. hyopneumoniae and some secondary respiratory pathogens may have been involved in the development of these pneumonias. PMID- 8451830 TI - Influence of adjuvants on the immune response of sheep to a novel Staphylococcus aureus vaccine. AB - Sheep were immunized twice with two Staphylococcus aureus vaccines which contained either killed bacterial cells shrouded with pseudocapsules or toxoided beta haemolysin, together with various adjuvants. Circulating antibody responses were monitored using an ELISA (anti-pseudo-capsule responses) and an anti-beta haemolysin assay. Combining a killed cell/pseudocapsule/dextran sulphate (DXS) vaccine and the toxoid vaccine did not cause any diminution of antibody responses compared with separate injection of the two preparations. Addition of calcium phosphate to DXS as an adjuvant for the combined vaccine did not extend the duration of anti-pseudocapsule responses compared with those obtained with dextran sulphate alone. Nor was there any benefit in terms of durability of the response by increasing the amount of DXS: doses of DXS of 10-20 mg/kg liveweight provoked significantly higher peak responses but caused acute clinical reactions at the vaccination site and did not prolong the antibody response. In contrast, the combined vaccine given with DXS and emulsified in Freund's Incomplete Adjuvant (FIA) resulted in a large anti-pseudocapsule response with elevated levels of antibody being sustained for at least one year; there was a significant IgG2 anti-pseudocapsule response in animals receiving the vaccine with DXS and FIA. In the above experiments, 10(10) pseudocapsule-shrouded bacterial cells were used in the vaccine. Reducing the concentration of cells to 10(9) caused a slightly reduced anti-pseudocapsule response (not significant) whereas increasing the concentration to 10(11) did not increase the response. PMID- 8451832 TI - Protection of Pasteurella multocida dermonecrotic toxin-challenged rats by toxoid induced antibody. AB - Two different doses of glutaraldehyde-treated Pasteurella multocida dermonecrotic toxin (PMDT) were used to immunize rats. Rats developed serum IgG antibodies specific for native PMDT, and IgG titers increased with dose and number of toxoid immunizations. Survival rates in both active immunization and passive serum neutralization experiments were dependent on dose of toxoid vaccination and serum levels of anti-PMDT IgG. Vaccination with toxoid prevented weight loss but not leukocytosis and increased complement titers in toxin-challenged rats. Toxoid, itself, induced minimal leukocytosis but no alterations in complement titers or weight gain. PMID- 8451833 TI - Recognition of Mycoplasma canis as part of the mycoplasmal flora of the bovine respiratory tract. AB - Mycoplasma strain C3b was isolated in the Netherlands from the lung of a pneumonic calf. Forty similar strains were isolated afterwards from calves in 19 other herds in different parts of the Netherlands. Eight strains from eight different herds were investigated in this study. Results of tests to determine whether the organism catabolized glucose were inconclusive. Four strains, including strain C3b, apparently catabolized glucose under some test conditions; the remaining four strains did not. Although strain C3b and similar strains were slightly different from canine M. canis strains in growth inhibition tests and glucose metabolism tests, we concluded that strain C3b and similar strains have to be classified as M. canis. A close contact between calves and dogs was observed in several herds where strain C3b or similar strains were isolated. This is the first report of M. canis isolated from cattle. PMID- 8451834 TI - Purification of hemagglutinin from Haemophilus paragallinarum using monoclonal antibody. AB - The purification of hemagglutinin from Haemophilus paragallinarum was attempted using affinity chromatography with monoclonal antibody. The antigen eluted from the affinity column using potassium thiocyanate buffer agglutinated chicken erythrocytes. In immunoblotting of the eluted antigen, a single band with monoclonal antibody was found as well as the crude antigen. When the chickens were immunized with the eluted antigen, they produced the hemagglutination inhibition (HI) antibody, and they showed protection against challenged exposure with H. paragallinarum strain 221. These results indicated that the HA antigen of H. paragallinarum was a protective antigen. PMID- 8451835 TI - Spatial reconstruction of signals from short-wavelength cones. AB - Because the retinal cone mosaic samples an image only at discrete locations, our continuous visual percept must arise from a spatial reconstruction process. How this process combines information from the three cone types is presently unclear. To investigate, we asked whether L and M cone information can modify the visual system's reconstruction of signals from S cones. In Expt 1, we used a matching paradigm to measure the effect of L and M cone information on filling-in at the foveal tritanopic area. We found that a small luminance disk superimposed at the tritanopic area decreases the amount of filling-in, showing that the reconstruction of S cone signals can be influenced by the spatial pattern seen by the L and M cones. In Expt 2, we asked whether L and M cone information can modify the splotchy low-frequency alias seen when an observer views fine S cone gratings. Here there was no evidence for an interaction. We conclude that though L and M cone information can influence the visual system's reconstruction of S cone signals, this influence may be confined to relatively coarse spatial patterns. PMID- 8451836 TI - More than three different cone pigments among people with normal color vision. AB - A fundamental feature of normal color vision is that red and green lights can be mixed to appear identical with a monochromatic yellow light. Another characteristic of normal color vision is that people often disagree on the amounts of red and green needed in the mixture to exactly match the yellow. Comparison of such color vision differences with photopigment gene differences reveals that a serine/alanine polymorphism at amino acid position 180 of X encoded pigments can account for this type of color vision variation. This amino acid change shifts the spectrum of the pigment produced by about 6 nm, a value that would predict a larger minimum color vision difference between individuals than is actually observed. This discrepancy can be explained if, counter to the Young-Helmholtz theory as the explanation of trichromacy, many people with normal color vision have more than three spectrally different cone pigments. PMID- 8451837 TI - What does post-adaptation color appearance reveal about cortical color representation? AB - We examine the implications of the hypothesis that color information in the cortex is adaptively coded into a factorial (statistically independent) and gain controlled representation. We show that this hypothesis explains the results of the recent experiments by Webster and Mollon [(1991) Nature, 349, 235-238] on changes in color appearance following post-receptoral adaptation. We also give a neural network with a deterministically convergent, unsupervised learning algorithm that reproduces the adaptation observed. PMID- 8451838 TI - Rank orderings of photoreceptor photon catches from natural objects are nearly illuminant-invariant. AB - To examine the potential contribution of first-stage photoreceptor adaptation to color constancy, photon catches from 337 natural objects illuminated with phases of daylight and tungsten light were calculated for a model human fovea. The rank ordering of these photon catches within each cone photoreceptor class was examined. When first-stage adaptation is modeled using multiplicative or subtractive mechanisms, or a monotonic nonlinearity, no reordering of the rank ordering of photon catches is possible across illuminant changes. The observed rank orderings remained nearly invariant across illuminant changes for all three photoreceptor classes, although there was some local shifting in the rank orderings, thus ruling out the ability of von Kries adaptation alone to produce perfect color constancy. This means that for objects with natural reflectance spectra, the ordinal relationships between the photon catches within a class of photoreceptors exhibit only minor changes for these illuminant shifts. This result may be attributable to the fact that approx. 95% of the variance in these reflectance spectra is captured by the first principal component; objects that produce relatively few absorptions under one phase of daylight illumination will also produce relatively few absorptions under another phase. A geometric formalism for understanding these relationships is presented, and limitations on this analysis are discussed. PMID- 8451839 TI - Both the phase and the amplitude spectrum may determine the appearance of natural images. AB - Several studies have demonstrated that the appearance of a natural image is determined mostly by its global phase spectrum; the amplitude spectrum is regarded as providing little specific information. In this paper, we show several cases where the global amplitude spectrum is also essential for specifying the particular content of natural images. Thus, both the amplitude and the phase spectrum may be important for reliable specification of such images. The results suggest that, although the average amplitude spectra of different natural images may be similar in their overall form, a realistic description of the amplitude spectra must also incorporate the particular way in which the energy is distributed across different orientations. PMID- 8451840 TI - An improved mathematical description of the foveal visual point spread function with parameters for age, pupil size and pigmentation. AB - An analytical description of the point spread function (PSF) for human foveal vision, together with its closed form two-dimensional Fourier transform, the modulation transfer function (MTF), is proposed. It also possesses an analytical line spread function (LSF) counterpart. It fits to both PSF and MTF experimental data and holds over the full angular and spatial frequency domain. Variation in the PSF and MTF descriptions with pupil size, age and iris/skin pigmentation are accounted for by analytical expressions in the parameters. PMID- 8451841 TI - Emmetropization as a first-order feedback system. AB - The existence of a regulatory mechanism that controls the growth of the eye toward emmetropia is generally agreed upon, but such an emmetropization mechanism has never been verified experimentally. This report supports the hypothesis that emmetropization can be described as a feedback process with a first-order equation and establishes a theoretical framework for future study, experimentation, and manipulation of this elusive mechanism. The feedback hypothesis has been tested by comparing two models. The first is a first-order feedback system, the second a non-feedback model with an almost identical equation. The feedback model fits data from human subjects significantly better. PMID- 8451842 TI - What part of a vernier stimulus determines performance? AB - Vernier acuity was measured using a pair of long, abutting vertical sinusoidal luminance gratings. Performance was also measured for pairs of thin horizontal strips of grating whose vertical separation was varied in order to represent different parts of the original grating. At small strip separations, performance was equivalent to that for the long gratings only at high spatial frequencies. At moderate spatial frequencies, intermediate strip separations resulted in equivalent performance. This suggests that different parts of a vernier stimulus can mediate performance depending upon the underlying spatial frequency content. Implications for the effect of contrast upon different vernier configurations are examined. PMID- 8451843 TI - Peripheral temporal frequency channels code frequency and speed inaccurately but allow accurate discrimination. AB - Perceived temporal frequency is vastly underestimated in the peripheral visual field, as all temporal frequencies above 10 Hz are perceived as flickering at 10 Hz even after scaling for acuity. Varying the contrast and spatial frequency of the peripheral pattern four-fold have negligible effects on the perceived flicker rate. Speed and auditory matching experiments also support this finding. Despite the saturation of perceived temporal frequency, frequency discrimination beyond 10 Hz was as accurate as in the fovea. By using a temporal masking paradigm, we obtained threshold elevation data that could be accounted for by three overlapping, broadly tuned temporal channels peaking at 5.5, 12 and 22 Hz. Based on these temporal frequency channels, we proposed that the visual system uses a line-element scheme for mediating temporal frequency discrimination, but adopts a weighted-average method for determining perceived temporal frequency. In the peripheral visual field, the weight assigned to the highest temporal channel is much larger than those assigned to the lower frequency channels. PMID- 8451844 TI - Properties of the visual channels that underlie adaptation to gradual change of luminance. AB - Following adaptation to a spatially uniform patch of light that is gradually brightening (or dimming), a steady test patch appears to be gradually dimming (or brightening). We measured this ramp aftereffect with a nulling method, as a function of the amplitude and temporal repetition rate of the adapting sawtooth waveform and at various retinal eccentricities and levels of dark adaptation. We conclude that the underlying visual channels respond best to large-amplitude sweeps in luminance of at least 20 dB (1 log unit); but they are fairly insensitive to the temporal rate of this sweep. The channels are present out to an eccentricity of at least 40 degrees but they almost disappear during dark adaptation. The ramp aftereffects were asymmetrical: the subjectively darkening aftereffect produced by a brightening adapting ramp was slightly stronger than vice versa. PMID- 8451845 TI - Interactions between short-term vertical phoria adaptation and nonconjugate adaptation of vertical pursuits. AB - We have demonstrated that short-term vertical position-specific phoria adaptation contributes to nonconjugate adaptation of vertical pursuits, but not to nonconjugate adaptation of vertical saccades. Binocular adaptation to multiple stationary vertical disparities resulted in both nonconjugate pursuits and phoria aftereffects but had little effect on the early step component of vertical saccades. Similarly, binocular nonconjugate adaptation of vertical pursuits produced both nonconjugate pursuits and fixation phoria aftereffects. Position specific adaptation of nonconjugate pursuit was demonstrated by adapting to disparate motion in the upper field which resulted in nonconjugate pursuit aftereffects that were greater in the upper than the lower hemifield. These nonconjugate pursuits were accompanied by position-specific phoria aftereffects, indicating that common mechanisms underlie adaptation of vertical phoria and nonconjugate pursuits. PMID- 8451846 TI - Directionally selective short-term nonconjugate adaptation of vertical pursuits. AB - We investigated the contribution of fixation phoria and dynamic processes to short term (1 hr) nonconjugate adaptation of vertical pursuits. Unequal aftereffects were observed in vertical phoria measured during stationary gaze and during pursuits (static fixation and pursuit phorias) demonstrating direction specific aftereffects of pursuit phoria that were not evident in measures of fixation phoria. A linear model describes the combination of fixation phoria and three dynamic direction-specific components which include a gain component that determines nonconjugate velocity, a phase component that determines the relative position of binocular pursuits, and a small position specific pursuit phoria adjustment process. Larger position-specific variations of fixation phoria appear to compensate for inappropriate or incomplete adaptive changes produced by two of the dynamic mechanisms which are not position specific. PMID- 8451847 TI - Spatial aspects of vertical phoria adaptation. AB - Vergence adaptation to vertical disparity spreads to unadapted directions of gaze. The spatial spread function for prism adaptation was estimated from aftereffects of a vertical disparity presented at a single position. Constraints limiting the spatial spread of adaptation were investigated with two stimuli of opposite disparity (hyper and hypo), presented at two different eye positions with a separation that varied from 6 to 18 deg in either the horizontal or vertical meridian. On average, phoria adaptation to the single point paradigm spread uniformly across the entire 18 deg test field. A resolution limit for adaptation to the two point paradigm was demonstrated by a reduction of phoria aftereffects with decreasing target separation (crowding). Vertical phoria aftereffects were reduced more by horizontal than by vertical crowding. A disparity gradient limit was demonstrated for a fixed target separation by a reduction of gain (phoria change/stimulus disparity) with increasing stimulus disparity. PMID- 8451848 TI - Express attentional shifts. AB - "Express" saccades, named for their extremely short latencies, occur more frequently in a paradigm with a "gap" in time between the disappearance of the fixation mark and the appearance of the target to be fixated. To explain this result, it has been hypothesized that movements of the eyes are preceded by movements of attention [Posner (1980) Quarterly Journal of Experimental Psychology, 32, 3-25], and that removing the fixation mark allows attention to disengage from the fovea and to be deployed more rapidly to the peripheral target, thus diminishing saccadic latency [Fisher (1987) Reviews of Physiology, Biochemistry and Pharmacology, 105, 1-35]. We measured attention using extra foveal vernier acuity performance. Our results provide direct evidence supporting the above hypothesis. First, we found that the rise of performance for increasing cue lead times was much faster in the "gap" paradigm. Second, the time function relating gap duration to discrimination performance was remarkably similar to the one relating gap duration and rate of express saccades reported by Mayfrank, Mobashery, Kimmig & Fischer [(1987) European Archives of Psychiatry and Neurological Science, 235, 269-275]. Third, control experiments showed that it was the disappearance of the fixation mark rather than a non-specific warning that led to more rapid shifts of attention and, thus, to better performance. We therefore conclude that the short latencies of "express" saccades may be based on a mechanism involving unusually rapid shifts of attention. PMID- 8451849 TI - Pop-out of orientation but no pop-out of motion at isoluminance. AB - Line textures in which one line was orthogonally oriented to the rest were briefly presented at various colour and luminance contrasts to the background. Subjects were able to detect the single line element pre-attentively even when the texture pattern was defined only by colour, indicating that "pop-out" of orientation is achieved at isoluminance. To exclude the possibility that this result was caused by luminance artefacts, especially by chromatic aberration, we carried out two control experiments. First, we showed that subjects could not detect a single moving line in a stationary texture under comparable conditions. Secondly, we repeated the experiments with a deuteranope who was unable to detect the differently oriented target under conditions under which the normal subject still could see it. PMID- 8451850 TI - [Is prevention really better than healing? A discussion contribution to prevention of spinal diseases]. AB - Primary, secondary and tertiary prevention are usually differentiated. All preventive measures have to prevail against criteria of effectiveness and efficiency. In the case of primary prevention, the search for risk factors is particularly important. The present limits of prevention of back pain are discussed in some detail; these exist mainly because at present our knowledge is incomplete. In the long run, prevention in the absence of a solid scientific basis is counter-productive. The only successful way of identifying effective preventive measures for back pain is to intensify research. PMID- 8451851 TI - Are single measurements of pseudocholinesterase and albumin markers for inflammatory activity or nutritional status in Crohn's disease? AB - Serum pseudocholinesterase (PCHE) activity and serum albumin concentration have been used as markers for inflammatory activity as well as malnutrition in Crohn's disease (CD) with controversial results. Therefore we investigated the valence of both proteins as markers of inflammation and/or malnutrition in 50 patients with active CD [Crohn's disease activity index (CDAI): median = 243; interquartile range = 191-288] and 70 patients with quiescent CD (CDAI: 62; 25-96). Thirty patients were malnourished, 18 with active [body weight: 84%; 79-88% IBW (ideal body weight)] and 12 with quiescent CD (87.5%; 81.5-88% IBW), and 90 patients were well nourished, 32 with active (96%; 93-112% IBW) and 58 with quiescent CD (104.5%; 96-116% IBW). Median values of PCHE activity and albumin concentration were within the normal range in both groups, in patients with active as well as quiescent CD. PCHE activity was decreased only in 24 patients (48%) with active, but also in 11 (15.7%) patients with quiescent disease. Albumin concentration was decreased in 12 patients (24%) with active and in one patient (1.4%) with quiescent disease. Comparing the two patient groups PCHE activity and albumin concentration were significantly lower in active than in quiescent CD [PCHE: 3.70 kU/l; 3.00-4.30 kU/l vs. 4.80 kU/l; 3.75-5.82 kU/l, p < 0.001; Albumin: 38.0 g/l; 35.1-39.9 g/l vs. 43.8 g/l; 40.8-46.3 g/l, p < 0.001]. Both proteins were significantly lower in malnourished than in well nourished patients, except albumin in patients with quiescent CD. Repeated measurements of PCHE and albumin in patients during and after active phases showed significant increases of both proteins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8451852 TI - [Canaliculitis: conservative versus surgical therapy]. PMID- 8451853 TI - [Comparative studies of the dimensional behavior of polymethylmethacrylate measuring systems with the 3-digitizer]. PMID- 8451854 TI - [Variants in calculation of future developments in the number of Alzheimer patients in Austria. Comment on the original contribution: Haidinger, G., Binder H., Kunze, M.: Developments in the number of Alzheimer diseases in Austria up to the year 2050]. PMID- 8451855 TI - [The Danube Hospital in the East Social Medicine Center. Planning, construction and completion]. AB - The Danube Hospital is part of a sociomedical center in East Vienna and was conceived to provide medical care for the transdanubian area of the city. In a planned stepwise operation both Depts. of Medicine, the Dept. of Surgery, the Dept. of Traumatology, the Dept. of Gynaecology and Obstetrics, the Dept. of Pediatrics, the Dept. of Pediatric Surgery, the Dept. of Neurology, the Dept. of Physiotherapy, the Dept. of Anaesthesia, the Dept. of Radiology, the Dept. of Laboratory Medicine, the Dept. of Nuclear Medicine, the Dept. of Pathology and Bacteriology, and the hospital pharmacy were opened in April 1992. Both the Dept. of Ear, Nose and Throat and the Dept. of Urology are due to open at the beginning of 1993, while the Dept. of Ophthalmology, the Dept. of Dermatology, the Dept. of Orthopedics, the Dept. of Maxillary Surgery and Dentistry and the Dept. of Neurosurgery will start operation in 1994. With the opening of the Dept. of Psychiatry in 1996 the Danube Hospital will be fully operative. By that time 920 beds, with an additional 59 functional beds (Intensive Care Units, Neonatology, Dialysis Ward, and Admission Unit) will be in operation. PMID- 8451856 TI - Ethics before profit. PMID- 8451857 TI - EVP report: the view from here up close and personal with health care reform. PMID- 8451858 TI - Fighting prejudice in the profession. PMID- 8451859 TI - HIV seroprevalence among patients attending a Milwaukee clinic for sexually transmitted diseases: findings from four annual surveys, 1988-1991. AB - Blinded HIV seroprevalence surveys were conducted annually from 1988 through 1991 among patients at a Milwaukee sexually transmitted disease (STD) clinic. Among 5,295 patients tested, 70 (1.3%) were HIV-1 Western blot positive. HIV seroprevalence rates were higher among male patients (1.7%) than among female patients (0.5%). HIV seroprevalence increased progressively with age and the number of prior STD episodes. During the four survey periods, HIV seroprevalence increased among teenage STD patients, patients who reported no prior STD, and patients without determined risk exposures. Selective voluntary HIV testing of patients who reported high risk exposures failed to detect 80% of all HIV seropositive patients. Because STD clinic patients are at high risk of HIV infection, HIV antibody testing, with appropriate referral of patients who test positive, and risk reduction education should be made routinely available to all STD patients with or without HIV-associated risk exposures. PMID- 8451860 TI - Trends in syphilis incidence in Wisconsin, 1985-1991. AB - Between 1985 and 1991, increases in early (infectious) syphilis occurred among Wisconsin residents (1.8 to 18.4 cases per 100,000 persons). Males represented 54% and females 46% of early syphilis cases. Increases in early syphilis morbidity occurred among both white residents (0.9 to 1.5 cases per 100,000 persons) and black residents (25.4 to 330.4 cases per 100,000 persons). The largest increases occurred in Milwaukee County; in 1990, 90% of the cases of early syphilis in Wisconsin occurred among residents of Milwaukee County. In 1990 and 1991, age-specific rates of early syphilis among Milwaukee County residents were highest in the 20- to 24-year-old age group. Increases in early syphilis are likely to be due to increased participation in high risk behaviors. Between 1985 and 1991, congenital syphilis increased among all Wisconsin infants (1.4 to 38.9 cases per 100,000 live births), white infants (0 to 3.3 cases per 100,000 live births), and black infants (20.8 to 326.0 cases per 100,000 live births). Of the 28 mothers giving birth in Wisconsin in 1990 to infants meeting CDC criteria for congenital syphilis, 22 (79%) attended at least one prenatal care visit (mean, four visits; range, 1-10 visits). Of the mothers who attended at least one prenatal care visit, only 11 (50%) were tested for syphilis during their first prenatal visit, and 5 (23%) were not tested until the time of delivery. Inadequate prenatal screening for syphilis contributed to the increase in congenital syphilis. PMID- 8451861 TI - A study of inpatients with AIDS in Racine County. AB - Since the first patient with AIDS was reported in 1981, the incidence of this illness has continued to rise. It is estimated that the cost of AIDS-related illnesses will be $15.2 billion by 1995. In this paper, we analyzed the number of admissions for AIDS to St Mary's Medical Center and St Luke's Hospital, both in Racine, Wis. Similar to the national trend, a rising incidence for hospital admissions was noted during the last 2 years. The rate of increase per year in this country was 31%, which is well above the national rate of increase. Twenty nine admissions for 19 patients occurred during the past 5 years. One third of these patients moved to Racine from other states. Apparently, 10% of the patients contracted their illness through heterosexual contacts. PMID- 8451862 TI - Newborn screening for congenital adrenal hyperplasia in Wisconsin. AB - Beginning in February 1993, newborn screening for 21-hydroxylase deficiency congenital adrenal hyperplasia (21OH-D-CAH) will begin in Wisconsin. This brief review summarizes the pathophysiology of 21OH-D-CAH, its clinical presentation, and the rationale for screening during the neonatal period. An algorithm for interpretation and follow-up of screening results is provided for Wisconsin health care providers. PMID- 8451863 TI - The Clinical Laboratory Improvement Act of 1988. PMID- 8451864 TI - Trends in cancer mortality among Wisconsin women, 1970-1990. PMID- 8451865 TI - [Public health: an interdisciplinary challenge]. AB - Presented as an opening lecture of the new postgraduate education programme of both the Technical and the Free University of Berlin, sponsored by the German Federal Minister of Research and Technology, this lecture recalls the foundation of the first School of Public Health (The Johns Hopkins School of Hygiene and Public Health, Baltimore, Md., USA) by William Henry Welch, 75 years ago. Already in this early experience, several central topics of Public Health can be traced back: for instance the exact description of health problems of total population groups, the aetiological understanding of health problems as well as the transfer of knowledge in public health programmes. After a definition of the Public Health concept both in- and outside Germany, the article reviews three examples of core topics of Public Health. Drawing on results from the first report "Health of Zurich", applications of descriptive epidemiology for both priority finding in Public Health as well as aetiological research are illustrated. The second example, with data from a recent representative survey of adults swiss germans on the issue of discrimination against persons infected with HIV draws attention to the central importance of social sciences within Public Health. Finally, the third example discusses recent advances in health services research, including issues of health economics, an other important part of an interdisciplinary Public Health understanding. PMID- 8451866 TI - [Prevalence of symptoms in selected diagnostic groups in teachers]. AB - In the context of occupational medical screening, teachers in the age groups up to, and older than, 45, were examined under a standardized medical programme in 1987 (22,240) and in 1988 (25,934). The relative risk within these groups for various illnesses was compared with data from investigations with other workers also examined in the former German Democratic Republic (over 400,000 yearly). As was the case for other occupational groups, the most frequently occurring symptoms were related to the musculoskeletal and cardiovascular systems. Teachers in both age categories showed a higher risk for illnesses of the nervous system, especially psychic disturbances and neurosis, and kidney and bladder diseases; male teachers showed a higher risk for cardiovascular diseases, and female teachers for diseases of the respiratory system. Elevated relative risks were already apparent in the group up to 45 years; for diseases of the nervous system the risk increased even further in subjects in the older age category. The proportion of persons overweight was, among female teachers, markedly smaller than in other groups. PMID- 8451867 TI - [Index numbers of ambulatory care utilization. Methodical and content aspects of the value of survey data]. AB - Index numbers of the utilization of outpatient treatment are essential for differentiated health reporting. The established doctor fulfills nodal, coordinating and regulating functions. Therefore numbers reflecting those functions are also indicators for other types of health services. They allow conclusions about motives, preferences and attitudes of the population. Based on two representative population surveys (the Socio-economic Panel and the National Health Survey of the German Cardiovascular Prevention Study) the index numbers Quarterly-Utilization, Contact-Frequency and User-Frequency are analysed. Taking the example of age and sex differences the influence of differing research designs on the validity and possibility of interpretation of the different index numbers are discussed. PMID- 8451868 TI - Child health promotion: a task for social pediatrics. AB - Health implies broad and positive aspects of life, well beyond disease and medical care. It is clearly expressed in the constitution of the WHO, and has been clarified in the Health for All strategy, emphasizing health promotion as a basic means to enable people to increase control over their health. The study of the broad and complex issues of population health is called public health; it naturally also includes children and their special needs. The ideology of Health for All, the science of public health and the imperatives of children's health are integrated in Social Pediatrics. Its task is to place the health of children in a full social, economic and political context, using inter-disciplinary, interprofessional and inter-sector cooperation with the children and their parents as the basis for all activities. After relating a few successes of socio pediatric actions on a national level, the focus is directed towards health promotion issues that are especially significant for children and young persons, i.e. fundamental, academic and practical issues. The way ahead for children's health promotion and for Social Pediatrics lies in the readiness to anticipate change and to adapt to new societal needs. PMID- 8451870 TI - [KOPS: a self-rating instrument for assessment of physical, psychological and social communication impairments]. AB - In this article the development of a self-rating symptom questionnaire is described. The questionnaire records physical, psychological and social interactionary impairments typical for neurotic and psychosomatic disorders. Contrary to most of the established self-assessment instruments the KOPS questionnaire consequently records symptoms from these three areas. The questionnaire contains 64 items scaled on four steps and can be filled out by the test person in a short period of time. The results depicted here from different sample groups which were examined verify the differential and criterion related validity and furthermore an explorative factor analysis also verifies the content validity. The instrument is suited for screening purposes as well as for clinical course studies of psychological disorders. The problems of the assessor perspective (by an expert or by a patient) in recording symptoms is discussed. PMID- 8451869 TI - Hip fracture mortality and morbidity in Switzerland and Japan: a cross-cultural comparison. AB - Based on national mortality data, the frequency of hip fractures in elderly people was compared between Switzerland and Japan. Age-adjusted annual incidence rates per 100,000 population estimated for Swiss persons over 60 years were around 150 and 200 in males and around 450 in females, while for the Japanese they were only 132 in males and 285 in females. Age-adjusted death rates from hip fracture for the Swiss over 60 were 20.0 in males and 28.9 in females, while for the Japanese they were only 1.6 in males and 2.7 in females. The inclination of the age-dependent slope in hip fracture mortality rates was substantially the same in both countries, but there was a "lag time" of approximately 10 years in Japan. Remarkably, the proportion of deaths due to falls among all accidental deaths was several times greater in both sexes for the Swiss than for the Japanese. This differential might be an important underlying reason for the observed difference between death rates of hip fracture in Switzerland and Japan. Other known behavioral risk factors for hip fracture such as diet, exercise, estrogen use etc. are unlikely to explain the observed difference in hip fracture mortality and morbidity between Switzerland and Japan. However, given the doubts on the reliability and thus comparability of the available data on mortality and morbidity, the present findings should be regarded as preliminary. In conclusion, we believe that the unexplained and large difference in the burden of hip fracture between Switzerland and Japan merits further studies, including new aetiological hypotheses. PMID- 8451871 TI - [The importance of psychosocial oncology in the treatment of cancer patients]. AB - Better medical care leads to an increased life expectancy but also to a growing psychosocial burden on the patients and their relatives. This development has led to the establishment of a new discipline: "Psychosocial Oncology". The psychosocial support of patients and their relatives as well as of nurses and physicians is described using the psychosocial aftercare unit attached to the department of surgery of the Heidelberg University Clinic as an example. Generally speaking two types of co-operation are possible-the consultation model and the integrated liaison model. Of these the latter seems to be the most appropriate but also the one most vulnerable to dysfunctions caused by professional and personal rivalries. In this paper the conditions necessary for a patient centered co-operation are discussed. If these requirements are met the patient centered approach, described by the three aspects of support, counseling and psychotherapy can be successful. PMID- 8451872 TI - [Expectations of treatment in a psychosomatic clinic]. AB - Expectations of patients staying in a psychosomatic clinic differ in a wide range. At first the structure of the expectations was studied. We then were able to separate 4 groups differentiated by different aims. Further analysis concerned the different expectations of this groups and that of the staff and of the GP or psychiatrists referring to the clinic. PMID- 8451873 TI - [Application of the Relationship Episodes Interview]. AB - The Core Conflictual Relationship Theme (CCRT) is a content analytic assessment developed by Luborsky that uses narratives about relationship episodes with significant others as data base to identify repetitive relationship patterns that appear in individual behavior. Luborsky's Relationship Anecdotes Paradigm (RAP) Interview for which we introduced the German expression Relationship Episodes Interview (RE-Interview) is a method for eliciting relationship episodes independently from therapy. In this paper we give an introduction into the practice and into the possible applications of this interview form according to the experiences the Ulm CCRT-group made with the instructions of Luborsky. The bases of our experience are 40 audio-visual recorded RE-Interviews. An example shows how to attain to the CCRT-formulation from the interview. PMID- 8451874 TI - [The correlation of sexual science and psychoanalysis]. PMID- 8451875 TI - [Free play and setting limits in inpatient psychotherapy]. AB - Some neglected issues of therapeutic technique in psychoanalytic inpatient therapy are reflected including their developmental and social psychological backgrounds (playing, power). Questions of dealing with an obligatory therapeutic frame supporting structural development are discussed with regard to team processes (rules of the ward). PMID- 8451876 TI - [Founding a work group. "Operationalized psychodynamic diagnosis"]. PMID- 8451877 TI - [Labeling of yeast protoplasts by neutral red and nile blue for fusion experiments]. AB - Neutral red and Nile blue were found to be suitable for staining protoplasts from various strains of Saccharomyces cerevisiae. The absorption of stains by the protoplasts was dependent on the pH value, for both stains. At a pH of 7.9 the protoplasts of the fusion partners could be stained differently and therefore it was possible to observe the fusion between the various strains of yeast. Consequently the prerequisites were created for the following micromanipulation. PMID- 8451878 TI - Microbial biomass-persistence relationships of acifluorfen in a clay-loam soil. AB - The interference of the effect of the herbicide acifluorfen on microbial biomass and on hydrolytic capacity, and its persistence in a clay-loam soil before and after enrichment with glucose, were investigated. The experiment was carried out under laboratory conditions for 120 days. Acifluorfen was added to the soil at two different application rates corresponding to 1X and 10X the recommended field rate. Biomass-C was significantly higher in the enriched soil during the first 35 days; subsequently there was a tendency to return to the original value of the unenriched soil. The herbicidal treatments depressed the biomass-C level, particularly at the higher rate. The hydrolytic capacity, measured as FDA hydrolase activity, was significantly higher in the enriched soil than in the unenriched soil. This was enhanced by acifluorfen treatment, chiefly at the higher rate. The degradation trend of acifluorfen was not significantly different at the two rates, but was significantly faster in the enriched soil. Half-life values of 28 and 40 days were found in the enriched and unenriched soil, respectively. PMID- 8451879 TI - Characterization of viable but nonculturable stage of C. coli, characterized with respect to electron microscopic findings, whole cell protein and lipooligosaccharide (LOS) patterns. AB - Campylobacter coli CK 205, isolated from swine feces, was examined for changes in cell morphology, protein and lipooligosaccharide (LOS) patterns during starvation survival experiments. Bottles filled with sterile filtered A. dest. were seeded with campylobacters and incubated at 4 degrees C and 37 degrees C. Transition to the nonculturable stage occurred within 48 hours (37 degrees C) and 2 weeks (4 degrees C), respectively. In contrast to the culturability the electrophoretic studies showed no changes in whole cell protein or LOS patterns. The electron microscopic pictures revealed spiral and coccoid forms, partly with a slightly enlarged periplasmatic space or budding of the membrane. Totally intact non culturable spiral or coccoid forms might be regarded as dormancy forms that cannot be detected by conventional microbiological methods in water examination. PMID- 8451880 TI - Survival of Salmonella enteritidis during the manufacture of feta cheese made of pasteurized ewe's milk. AB - The behaviour of Salmonella enteritidis during the Feta cheese making process was investigated. Two lots of pasteurized whole ewe's milk were inoculated to contain 10(6) cfu/ml of S. enteritidis (strain AS1 and AS2) and were processed into Feta cheese following standard procedures. All samples were examined for S. enteritidis both quantitatively and qualitatively, while moisture, fat, water activity and pH were also measured. S. enteritidis was enumerated in duplicate samples by surface plating on SS agar. Selected salmonella-like colonies were identified biochemically and serologically. The enumerations have shown that S. enteritidis was initially entrapped in the curd. Then the growth of S. enteritidis gradually decreased and no Salmonellae were quantitatively enumerated after the 23rd day. However S. enteritidis was detected qualitatively in samples taken until the 38th day. PMID- 8451881 TI - [Healing of the anastomosis in various suture techniques in the gastrointestinal tract. Physiology, experimental and clinical results]. AB - New and further development of anastomoses induce new orientation for selection and indication of the several suture procedures in the gastrointestinal tract. Based on the wound healing principles, the different techniques are evaluated experimentally and in clinical tests. The results allow to discriminate indications for the different suture techniques. For the gastrointestinal tract the technique of choice is the serosubmucous single row suture with an absorbable 4.0 monofilament. For the esophagus and rectum, the stapled anastomosis offers more safety and better practicability than manual sutures. Studies have shown comparable results in colonic surgery for compression ring anastomoses. Additional procedures are of minor importance for the safety of anastomoses. PMID- 8451882 TI - [The cost aspects of organ transplantation]. AB - The costs of different transplantation procedures are analysed. The costs which are not covered by the regular hospital allowance are presented using kidney transplantation as an example. It can be demonstrated that the main costs of transplantation arise from post-operative medication. At the moment these costs are not completely covered by the special remunerations for kidney transplantation. Nevertheless kidney transplantation is the most cost-saving of all kidney replacement therapy procedures: during a three-year-treatment period a successful kidney transplantation will save 53% of costs in comparison to home dialysis, 49% compared to CAPD and 61% in the case of Limited-Care-dialysis. PMID- 8451883 TI - [Management of acute craniocerebral trauma]. AB - The first step in the management of acute head injury is the maintenance of circulation and respiration. In case of surgical intervention correct timing is necessary. Postoperative monitoring and intensive care are important to maintain sufficient brain circulation. PMID- 8451884 TI - [Ambulatory surgery interventions in childhood in a surgical clinic]. AB - Between Jan. 1, 1980 and Dec. 31, 1990 1 688 children underwent One-Day-Surgery at the Surgical Department of the Rhenish-Westfalian Technical University. More than 85% of the operations were inguinal hernias (n = 765), phimoses (n = 324) and umbilical hernias (n = 185). The children's age ranged from 3 months up to 14 years. 27 patients (1.6%) could not be dismissed at the same day because of early complications. Two postoperative hemorrhages after circumcision led to readmissions and reoperation. More than 90% of the parents and 85% of the pediatrists were satisfied with the One-Day-Surgery. A responsible and successful One-Day-Surgery needs qualified surgeons, a well defined organizational structure and the observance of forensic problems. PMID- 8451885 TI - [Surgical treatment of bleeding stomach and duodenal ulcer--retrospective analysis of a five-year period]. AB - 94 patients have been operated upon for haemorrhagic gastroduodenal ulcer disease in the Wenckebach-Krankenhaus during the years 1986-1990. In all but 6 patients the ulcer has been controlled by an emergency gastroscopy. 25 of these patients had to undergo emergency operation at once for persistent bleeding after gastroscopy. From the other patients, another 31 suffered rebleeding and had to be laparotomised in an emergency procedure, too. Only in 38 cases an interval operation was possible. No one of these 38 patients died. The overall mortality rate was 14.9% (14 patients). The mean age of our patients was 68 (26-90) years, none of the patients under 60 years died, whereas the mortality-rate of the elder was as high as 20%. The operative procedures were ulcer excision and suturing of the bleeding vessel and distal gastrectomy. There was no difference in mortality rates between resective and non resective procedures. Our aim to operate upon the patients in an elective way could be achieved in about one third only. Many patients refused an operation after primary control of bleeding. PMID- 8451886 TI - [Use of laparoscopic surgical methods in mechanical ileus of the small intestine and in stomach perforation]. AB - We report on the application of laparoscopic operative methods in ten patients with mechanical bowel obstruction and in seven patients with gastric perforation. From these experiences conclusions were drawn concerning the principles of trocar positioning as well as tactical and strategical considerations in acute abdominal surgery with known and unknown target regions. PMID- 8451887 TI - [Risk factors of perioperative morbidity and mortality in colorectal cancer with special reference to tumor stage, site and age]. AB - The perioperative risk was prospectively analyzed in 511 patients with colorectal cancer, out of which 5% had an emergency procedure. The morbidity rate was 23.6% without an association with tumour stage or localization. The incidence of nonsurgical complications rose with increasing age because of a rising number of concomitant illnesses (< 50: 5.7%, > 80: 28.1%). The morbidity was associated with an increasing blood loss during the operation (< 500 ml: 10.6%, > 2000 ml: 30.4%), but not with the type of treatment. The overall operative mortality rate was 2.3% with the same rate of surgical complications and complications of preexisting conditions. Morbidity and mortality following emergency procedure were 56%, respectively 20%, expressing mainly septical complications of colorectal cancer. PMID- 8451888 TI - [Tracheal and bronchial rupture after blunt thoracic trauma]. AB - Airway disruptions after blunt chest trauma are rather infrequent with an incidence of about 1%. Even in large centers with many such casualties they are episodical. The clinical picture is not an uniform one, and typical clinical signs occur often without an airway lesion. Therefore, the correct diagnosis may be delayed. Two case reports, one with a tracheal rupture, the other with complete disruption of the main right bronchus are presented. Both patients showed significant soft tissue emphysema, increasing dyspnea and hypoxia respectively within a few hours after their accident. The diagnosis was established bronchoscopically after time intervals of 8 and 32 hours respectively, followed by immediate surgical correction. Both patients experienced a smooth recovery with good longterm results. In blunt chest trauma presenting with subcutaneous emphysema, pneumomediastinum, pneumothorax, hemoptysis and respiratory distress, tracheobronchial disruption should be considered. In this case, expert bronchoscopy, preferably by a surgeon with large thoracic experience, is mandatory. PMID- 8451889 TI - [Endoscopic surgery--economic aspects from the viewpoint of a university clinic]. AB - In this overview minimal invasive surgery as demonstrated by endoscopic cholecystectomy is audited in comparison to conventional surgery as regards economic efficiency in the view of an university hospital. The costs of investment are significantly higher for minimal invasive surgery compared to conventional surgery, but the running costs are nearly identical for both procedures. Most decisive is the influence of minimal invasive surgery on the postoperative hospitalization time: by cutting this time the quantity of available hospital beds has to be reduced (in the case of invariable number for patients), however, this has no dramatic influence on the size of the surgical department. PMID- 8451890 TI - [The value of continuous wave Doppler ultrasound in risk pregnancy-intrauterine growth retardation and pregnancy-induced hypertension]. AB - To evaluate the frequency of abnormal doppler results in pregnancies complicated by placental insufficiency, flow waveforms of 100 patients with documented intrauterine growth retardation--birthweight below the 10th percentile--were analysed. Uterine, arcuate and umbilical artery velocimetry were performed by means of a continuous wave Doppler ultrasound. Neither the range of serial examination nor the interval between last prepartal doppler test und delivery showed influence on the doppler results. Compared to normal pregnancy, a significant increase of diastolic notching and incomplete registration of maternal vessels were found. Using 90th percentile as cut-off limit last doppler examination before delivery showed pathological results in 76% of all cases with growth retardation and 90% of pregnancies with an additional risk of pregnancy induced hypertension. As pathological waveforms in the maternal compartment contribute a major part to abnormal velocity waveforms, doppler study of utero placental vessels plays an important role in the diagnose of impaired persuasion of the placenta. PMID- 8451891 TI - [Assessment of hemodynamics in the cerebral cortex in newborn infants]. AB - Determinations of blood velocity in vessels of cerebral cortex have been done using a 20 MHz impulse Doppler unit. In comparison we registered the blood flow pulsation curves at the anterior cerebral artery with aid of a 5 MHz-cw-Doppler system. The peripheral resistance index was calculated and it could be proved a strong correlation between the results of the anterior cerebral artery and the vessels of cerebral cortex. Another study showed that the results of the method could be reproduced. The problem of the impulse Doppler examinations of cerebral cortical vessels is the fact, that the exact topography of the vessels examined cannot be defined exactly. PMID- 8451892 TI - [Value of perinatal characteristics for diagnosis of perinatal infections]. AB - A retrospective case control study was performed in order to evaluate the diagnostic validity of clinical and paraclinical signs for early detection of neonatal sepsis. The perinatal data of 45 newborns with sepsis on day 1 or 2 (early perinatal sepsis) after birth were compared with those of 34 newborns with sepsis on day 3 and 4 (late perinatal sepsis) and with 87 newborns as controls. The groups were comparable in respect of birth weight (1,972-2,114 g), gestational age (33.3-33.5 weeks), gender (prevalence of male), frequency of prematures (82-91%) and mode of delivery. In cases of early perinatal sepsis a significant higher incidence of fetal tachycardia was found (heart rate > 160/min in 50% versus 5% in late perinatal sepsis and 8% in controls respectively), of reduced fetal heart oscillation (56% versus 14 and 38%) and of loss of acceleration (76% versus 56 and 20%) in the CTG ante partum. Therefore, these signs have proved to have a better diagnostic validity for infection than premature rupture of membranes, a prolonged rupture of membranes and the chorioamnionitis. Another predominant finding was the significant greater need for resuscitation due to asphyxia (48% in early sepsis versus 14 and 7%) despite missing differences in pH of blood in umbilical artery at birth (7.28 +/- 0.07). The occurrence of such signs supports a suspicion of a fetal sepsis. PMID- 8451893 TI - [Clinical results of pediatric gynecologic consultation at the Heidelberg University Gynecologic Clinic]. AB - During the research period from January 1984 through June 1991 649 patients between the age of 0 and 16 were examined. Divided into 13 diagnostic groups the vulvovaginitis occurred most frequently with 30.6%. The predominant causal agents were E. coli (18.1%) and streptococci B (11.5%). Almost 24% did not show any agents. Aside from malformations of the genitals (6%), the genital bleedings (8.3%), genital tumours (2.7%), the search for anticonceptives (7.5%), examinations by specialists (8.1%) and borderline surgical problems, cycle disorders (14.7%) were most frequent. Among the cycle disorders dysmenorrhea and oligomenorrhea were predominant. The hormonal inhibition of growth was also checked very carefully. Thus the necessity of well-aimed training of children's gynaecology becomes dear. Our results stress the importance of an intensive disciplinary contact between gynaecologists who are interested in pediatrics and pediatricians. PMID- 8451894 TI - [Perioperative preventive use of antibiotics in breast surgery: clindamycin vs. cefuroxime]. AB - 149 patients scheduled for breast surgery with an identified risk for infection received either 1.2 g Clindamycin (n = 79) or 1.5 g Cefuroxim given intravenously in a prospectively randomized fashion at induction of anaesthesia. Both drugs were well tolerated by all study patients. Postoperative fever was seen in one woman in the Clindamycin group vs. two women in the Cefuroxim group (n.s.). Serum and tissue levels measured 30 minutes after administration were within the therapeutic range for both antimicrobial substances. PMID- 8451895 TI - [Cefuroxime and cefoxitin in perioperative preventive use of antibiotics. A randomized study]. AB - In a prospectively randomized study 243 patients scheduled for gynaecologic surgery received either 2 g Cefoxitin or 1.5 g Cefuroxim at induction of anaesthesia. Both drugs were well tolerated by all study patients. Post-operative fever was seen in seven women in the Cefuroxim group (n = 121) vs. three women in the Cefoxitin group (n.s., x2-test). Wound infection occurred in two women in each group. In result Cefuroxim probably can be recommended as an alternative replacing Cefoxitin in prophylaxis, so Cefoxitin can be reserved as potent antimicrobial substance for therapy of gynaecologic infections. PMID- 8451897 TI - [Report on the 22d Congress of the International Continence Society (ICS) 1-4 September 1992 in Halifax/Canada]. PMID- 8451896 TI - [HELLP syndrome in the 26th week of pregnancy]. AB - The HELLP-syndrome is the most severe form of pre-eclampsia. Fetal and maternal life is threatened because of missing prodromi and sudden onset of complications. This case report describes the development of HELLP-syndrome in a 26 y/o G1P0 in the 26th week of gestation. Clinical signs and changes in laboratory parameters lead to the diagnosis. No hypertension was stated. The pregnancy was terminated by cesarean section resulting in a viable 900 g female newborn, who was transferred to the neonatal intensive care unit. The patient's condition stabilized quickly after the delivery, symptoms decreased within 4 days. PMID- 8451898 TI - [International Symposium on Fetal and Neonatal Neurology. Tours 7-10 October 1992]. PMID- 8451899 TI - Ultrasonographic examination of the left kidney, the urinary bladder, and the urethra in cows. AB - The purpose of the present study was to determine the position, dimensions and structure of the left kidney, the urinary bladder and the urethra in cattle by use of ultrasonography. The left kidney, the urinary bladder and the urethra of 12 healthy, Swiss Braunvieh cows were examined transrectally using a 5.0 MHz linear transducer 10 times within two weeks. The lobulation of the kidney in cattle could be visualized ultrasonographically. The echogenicity of various renal structures differed. The renal cortex was hyperechoic in comparison to the relative hypoechoic renal medullary pyramids. The urinary bladder was always visible but its diameter varied greatly. The vertical diameter of the left kidney was 6.2 +/- 1.0 cm in the region of the renal hilus. In 7 cows the thickness of renal cortex and medulla was between 2.0 and 2.3 cm. The diameter of the renal sinus varied from 1.1 to 2.5 cm. The interassay coefficients of variation of the variables measured varied between 8.5 and 16.5%. It was concluded that the ultrasonographic values determined in this study can be used as references for the diagnosis of morphologic changes in the bovine left kidney. PMID- 8451900 TI - Effects of intraarticular corticosteroid and sodium hyaluronate injections on synovial fluid production and synovial fluid content of sodium hyaluronate and proteoglycans in normal equine joints. AB - Hyaluronate and cartilage proteoglycan fragments in synovial fluid from normal equine joints were determined after repeated intraarticular injections of beta methasone, methylprednisolone, hyaluronate, saline and a combination of beta methasone + hyaluronate and methylprednisolone + hyaluronate. The experimental intraarticular treatments were given at the beginning of the study and after one and two weeks. Synovial samples were obtained at the onset of the study and after 1, 2, 3, 4, 6, and 8 weeks. The synovial volume was determined and showed no significant changes after the repeated arthrocenteses and the experimental treatments. Corticosteroid injections resulted in increased levels of hyaluronate in the synovial fluid which indicated a stimulatory effect on the synoviocytes to produce hyaluronate. The corticosteroids also resulted in high levels (up to 20 times the initial level) of proteoglycans which indicated joint cartilage degradation. A combined injection of corticosteroids and high molecular weight hyaluronate reduced proteoglycan breakdown which indicated a protective effect of hyaluronate on the articular cartilage. PMID- 8451901 TI - Evaluation of an enzyme linked immunosorbent assay (ELISA) for determination of insulin in dogs. AB - The purpose of the present study was to evaluate an enzyme linked immunosorbent assay (ELISA) technique for the determination of insulin in canine plasma samples. The test kit Enzymun-Test (Boehringer Mannheim) for determination of human insulin was used in connection with the analyzer system Enzymum-Test (Boehringer Mannheim) System ES-33. The assay protocol suggested by the manufacturer was slightly modified by including an additional standard having a concentration within the canine reference range for insulin. Further, the incubation period for the immunoreaction and the enzymeassay was increased to 150 minutes and 90 minutes, respectively. When using the modified assay the concentration of insulin in canine plasma samples could be accurately and precisely determined with the exception, that the assay appeared to be somewhat imprecise (intraassay coefficient of variation being 22%) when lipaemic plasma samples were analysed. A slight overestimation of the actual concentrations (28%) was observed, but the measured concentrations of insulin in plasma samples from normal dogs compared favourable to those reported in literature. Eventually, a model for introduction of a species specific reference is discussed. PMID- 8451902 TI - Effects of oral and intravenous administration of endotoxin in prepubertal gilts. AB - The effect of oral intake of endotoxins was studied in 12 prepubertal gilts. The animals were given 30 or 100 mg of ET each in their regular morning feed ration. Blood samples were collected periodically during 24 h and the clinical status, including rectal temperature, was recorded at the same time. Hematological and clinical chemical analyses that included serum bile acids, glutamate dehydrogenase, alkaline phosphatase, calcium, iron, zinc and a blood plasma metabolite of prostaglandin F2 alpha, were done. The animals showed no obvious clinical symptoms following endotoxin feeding. The major findings were increased bile acid and glutamate dehydrogenase values with the most prominent rises being recorded 10-12 h after endotoxin intake. In a later experiment, 6 animals were injected i.v. with endotoxin in doses in the range 0.1-0.5 micrograms/kg b.w. Blood samples were taken and analysed as in the endotoxin-feeding experiment. Within 1 h of injection, all animals showed symptoms such as vomiting, fever and dyspnea. The clinical signs disappeared within 2-5 h. The injections were followed by increases in bile acids, glutamate dehydrogenase and prostaglandin F2 alpha metabolite. To conclude, this study indicates that clinically healthy prepubertal gilts react to ingested endotoxin in feed but that no apparent clinical disturbances ensue. PMID- 8451903 TI - Feeding of rapeseed presscake meal to pigs: effects on thyroid morphology and function and on thyroid hormone blood levels, on liver and on growth performance. AB - Effects of feeding soybean meal (SBM) or a mixture of SBM and 5%, 10% and 15% of either 0- and 00-rapeseed presscake meal (RPM) on thyroid, liver and growth performance were studied in castrated boars. Goitrin (G) intake was closely correlated with total glucosinolate intake and blood thiocyanate concentration. In pigs fed 10% and 15% 0-RPM refused feed was enhanced and daily gain decreased. Liver weight and DNA/total liver increased with increasing G intake. Thyroid weights increased up to a G intake of 4.6 mmol/d and then decreased with higher G intake. DNA content/g dry matter (DM) increased continuously and total thyroidal DNA content up to a G intake of 4.6 mmol/l, indicating hyperplasia. Epithelial thickness increased up to a G intake of 13.3 mmol/d, whereas follicular area only up to an intake of 4.6 mmol G/d and then decreased, mirrored by a decrease of DM content. Thyroidal thyroxine (T4) and triiodothyronine (T3) content decreased with increasing G intake. Blood serum levels of T4 decreased with increasing G intake, whereas T3 levels only tended to decrease. Therefore, measured parameters differently reacted to different G intake. In groups fed high amounts of G, hyperplasia was not sufficient to maintain physiological circulating T4 levels, but enhanced thyroidal secretion T3 and/or extrathyreoidal T4 to T3 conversion obviously allowed maintenance of near normal circulating T3 concentrations and barely reduced growth rate despite marked hypothyroidism. PMID- 8451904 TI - Polioencephalomalacia induced with amprolium in buffalo calves: pathologic changes of the central nervous system. AB - Eight apparently healthy male buffalo calves of 6 to 12 months of age were drenched with amprolium (300 mg/kg body weight) till the development of clinical signs. Four buffalo calves of the same age group were drenched with tap water only and these served as controls. Amprolium drenched calves were allowed to die after the onset of clinical signs and control calves were euthanised after the death of amprolium fed calves. Tissues were collected for histopathological studies. Formalin fixed brain slices were examined for autofluorescence with the help of ultraviolet light at 365 nm. Gross and histopathological changes were mainly confined to the brain in amprolium fed calves. Gross lesions included congestion and haemorrhages in the meninges. The cerebral gyri were swollen with yellowish discolouration of cerebral cortex. Microscopic changes in the brain were limited to gray matter structures of cerebral and cerebellar cortex, caudal colliculi of mid brain and thalamus. There was shrinkage of neurons, perivascular and pericellular edema, necrosis of neurons, satellitosis, glial nodule and gliosis. Blood vessel walls were thickened due to hypertrophy and hyperplasia of endothelial and adventitial cells. In the cerebellar cortex, there was degeneration of Purkinje cells. The caudal colliculi of mid brain showed bilateral malacia. In the necrotic areas, neuropils were fragmented, edematous and hypercellular due to increased number of microglial cells and there was neocapillary formation. Subcortical gray matter of the thalamus showed necrosis of neurons, gliosis with formation of glial nodule. Formalin-fixed brain slices of amprolium fed calves showed disseminated areas of greenish yellow autofluorescence in the cerebral cortex when viewed under ultraviolet light at 365 nm. PMID- 8451905 TI - Biochemical indicators of bone metabolic activity in bovine periparturient hypocalcemia. AB - Twenty-one paretic and 30 nonparetic periparturient ambulatory cows were studied together with 13 non-pregnant control cows. Blood samples were collected during a time period of 6 hours before or after parturition and from nonpregnant cows. A severe hypocalcemia (-44%) and hypophosphatemia (-69%) were found in the paretic vs. nonparetic periparturient animals, whereas serum magnesium concentrations were not altered. Serum alkaline phosphatase activity was modestly (-12%) but not significantly decreased in the paretic vs. nonparetic periparturient cows. Serum osteocalcin concentrations, which reflect osteoblast activity, were strikingly low during the periparturient period and more in the paretic cows but the difference between the paretic (-36%) and nonparetic animals was not statistically significant. In the paretic cows, serum 1,25-dihydroxyvitamin D concentrations were significantly increased (+53%) and those of hydroxyproline decreased (-18%) compared with the nonparetic animals. Serum estradiol levels were markedly increased in the periparturient vs. nonpregnant cows and more in the paretic animals, but, again, the difference between the paretic (+47%) and nonparetic animals was not statistically significant. Serum retinol concentrations were significantly lower (-18%) in the paretic vs. nonparetic periparturient cows probably reflecting increased lactation in the paretic animals. Collectively, the results indicate very low bone metabolic activity in the periparturient vs. nonpregnant cows and support the hypothesis of both osteoblast and osteoclast functions being impaired in the paretic animals. PMID- 8451906 TI - Nocturnal versus diurnal hormonal counterregulation to hypoglycemia in type 1 (insulin-dependent) diabetic patients. AB - Asymptomatic hypoglycemia in IDDM patients seems to be more frequent during the night than during the day, with reported frequencies as high as 56%. Hormonal counterregulation to diurnal and nocturnal hypoglycemia was studied in 10 insulin dependent diabetic patients without diabetic complications in order to test whether hormonal responses were lower at night than during daytime. A lower catecholamine response might imply less marked symptoms and therefore one reason why patients are not awakened by hypoglycemia. Blood glucose was stabilized to around 6 mmol/l by iv insulin infusion and hypoglycemia was induced by increasing the insulin infusion rate--in the night studies at 01.30, in the day studies at 08.00. Blood glucose nadirs were 1.5 +/- 0.4 (1.2-1.9) mmol/l at night and 1.9 +/ 0.3 (1.3-2.2) mmol/l during the day; in the three patients the nadirs were identical during both the night and day. One patient had no adrenaline response to daytime hypoglycemia. In general, nocturnal hypoglycemia elicited greater catecholamine responses correlated to the duration of hypoglycemia. Glucagon responses showed a great heterogeneity independently of diabetes duration and hypoglycemic level. Growth hormone secretion was reduced during the night study; however, no refractory periods were found after sleep-related growth hormone secretion. IN CONCLUSION: counter-regulatory hormonal responses tend to be greater at night than during the day and do not explain why patients are not awakened by nocturnal hypoglycemia. PMID- 8451907 TI - The "feto-maternal" thyroid function interrelationships in an iodine-deficient region in Africa--the role of T3 in possible fetal defence. AB - The thyroid status was investigated in 26 pregnant African women at term delivery in an iodine-deficient region (Jengere) of Nigeria, West Africa including the measurement of serum T4, T3, TSH, thyroxine binding capacity, TBG, free thyroxine index (FT4I) and the results were matched with those obtained in a corresponding group of 46 women at delivery in Jos, the non-iodine-deficient region which was used as a control. Corresponding cord-blood samples were obtained from all the neonates of the two groups. Twenty-three urinary samples in the former and 14 in the latter group were analysed for iodide levels to ascertain the degree of iodine deficiency. The results demonstrate that compared to the values seen in the Jos group the maternal serum T4, T3 and FT4I levels were significantly reduced in the iodine-deficient group, while TSH, TBG and thyroxine binding capacity were elevated. Cord serum samples showed a corresponding fall in T4 and FT4I levels in the group from the iodine-deficient region, while the T3 levels were significantly elevated with a concurrent significant rise in TSH and TBG levels. Significant correlations were found between the maternal and cord serum T4, TSH, TBG, thyroxine binding capacity and FT4I levels, but not T3. From these findings we suggest that fetal T3 plays an important defensive role against the danger of long-standing environmental iodine deficiency. PMID- 8451908 TI - Immunodetection of TSH receptor antibodies in sera of patients with autoimmune thyroid disease by ELISA (enzyme-linked immunosorbent assay). AB - An ELISA system has been developed for detecting antibodies to TSH receptor peptides. It has been used to study antibodies against peptides corresponding to four different extracellular domains of human TSH receptor in the sera of patients with Graves' disease (N = 10, TBII positive) and Hashimoto's disease (N = 10, TBII negative). Two peptides, N (amino acid residues nos. 29-57) and P3 (nos. 359-371) are specific for TSH receptor, and two, C (nos 172-202) and P1 (nos. 398-417) are homologous with the corresponding portions of the LH/CG receptor. All of the peptides were recognized by sera from patients with Graves' disease but individual sera recognized different numbers and combinations of these peptides. Sera from patients with Hashimoto's disease did not bind to any of these peptides. These results suggest that antibodies to the TSH receptor in patients with Graves' disease recognize various regions of extracellular domain of TSH receptor in addition to TSH receptor-specific regions. PMID- 8451909 TI - Altered adrenal steroid production in term infants having respiratory acidosis. AB - Prior studies have provided evidence for reduced fetal adrenal production of dehydroepiandrosterone sulfate and normal or increased production of cortisol in association with pregnancy complications believed to result in fetal stress. In the present study, we sought to determine the status of adrenal steroidogenesis in 36 term infants having respiratory acidosis and to compare acidotic infants to (i) non-acidotic infants matched for pregnancy complications, gestational age, and method and indications for delivery (control infants), and (ii) non-acidotic infants of non-complicated pregnancies who were also matched for gestational age and delivery method (normal infants). Umbilical cord serum levels of dehydroepiandrosterone sulfate were lowest in acidotic infants, intermediate in the condition matched control infants and highest in the non-acidotic infants of normal pregnancies. On the other hand, cortisol levels were highest in acidotic infants, intermediate in control infants and lowest in the normal infants. These data suggest that various pregnancy complications give rise to significant alterations in adrenal steroidogenesis (decreased dehydroepiandrosterone sulfate and increased cortisol). Intrauterine deterioration during labor with resultant respiratory acidosis has an additional effect on fetal adrenal function. PMID- 8451910 TI - Graves' disease, endocrine ophthalmopathy and smoking. AB - We have evaluated the association between smoking, Graves' disease and endocrine ophthalmopathy in a case-control study of 208 patients with newly diagnosed Graves' disease and carried out a retrospective survey of 72 patients treated for Graves' disease and admitted to our ward because of endocrine ophthalmopathy. In the prospective study, patients with Graves' disease smoked significantly more than their healthy controls (41% vs 30%, p < 0.01 for current smokers, odds ratio 1.6, 95% confidence interval 1.1-2.3, and p < 0.05 for patients with a history of smoking, odds ratio: 1.4, 95% confidence interval 1.0-1.9). Among the patients with endocrine ophthalmopathy at diagnosis, there were slightly more patients with a history of smoking (p < 0.05, odds ratio 2.1, 95% confidence interval 1.1 3.9), but not more current smokers when compared with the remaining group. The patients with eye problems tended to have a more active disease with higher levels of thyroxine and TSH-receptor antibodies, but no difference was seen in thyrogastric autoantibodies. No effect of smoking on thyroid hormone and autoantibody levels could be detected. In the retrospective survey we found 64%, 71% and 87% smokers among patients with moderate, severe and malignant eye disease, respectively. In summary, the results show that smoking is associated with an increased risk of contracting Graves' disease and that it enhances the severity of the eye disease in cases that develop endocrine ophthalmopathy during the course of treatment. PMID- 8451911 TI - Influence of steroid hormones on 5 alpha-reductase activity in female and male genital skin fibroblasts in culture. AB - The physiological regulation of 5 alpha-reductase (5 alpha R) as well as the complex pathogenesis of male and female androgenic disorders are still incompletely understood. Therefore, we examined the influence of various steroid hormones on the 5 alpha R activity in female and male genital skin fibroblasts in primary culture to test whether the 5 alpha R activity is identically regulated in genital skin samples of both sexes. Nine foreskin samples of male patients and 11 specimens of female genital skin were prepared and cultured as primary tissue cultures. After pre-incubation with various unlabeled steroids, [3H]-testosterone was added to the cultures and the 5 alpha R activity (conversion of testosterone to dihydrotestosterone) measured. (a) The pre-incubation of male foreskin fibroblasts with unlabeled androstenedione and androstandione both resulted in stimulation of 5 alpha R activity. Other unlabeled steroid hormones, including progesterone, testosterone, dihydrotestosterone, and estradiol had no significant effect on 5 alpha R activity. (b) In female genital skin fibroblasts, pre incubation with testosterone also led to an increase in 5 alpha R activity, whereas pre-incubation with estradiol decreased 5 alpha R activity. None of the other unlabeled steroid hormones applied had significant effects. These data on male foreskin in culture suggest a physiologic regulatory mechanism of 5 alpha R activity independent of the concentration of the enzymatic substrate or product, whereas the results for the female genital skin suggest a cellular regulation of the androgen levels by the enzymatic substrate testosterone and a possible negative feedback mechanism of estrogens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8451912 TI - Plasma levels of several androgens and estrogens from birth to puberty in male domestic pigs. AB - Plasma concentrations for several androgens and estrogens were determined in male domestic pigs from birth to eight months of age. Samples (N = 6) of blood were collected from Yorkshire males at weekly intervals from birth to four weeks, and thereafter at monthly intervals to eight months. Radioimmunoassays were done without extraction from plasma for dehydroepiandrosterone sulphate, androstenedione and estrone sulphate. Other steroids were measured after solid phase extraction, separate elution of unconjugated and conjugated fractions, and solvolysis of sulpho-conjugated steroids (testosterone, 5 alpha-androstane-3 beta, 17 beta-diol, epiandrosterone, 19-nortestosterone and estradiol-17 beta). All steroids showed a peak in plasma levels at 2-4 weeks after birth. Concentrations remained low from 2-5 months and rose markedly thereafter. Most steroids were present in much greater quantities as sulpho-conjugated compounds. Concentrations of testosterone sulphate and testosterone were similar (9.4 mumol/l) at three weeks but the sulphated form predominated after six months of age. This study shows that during postnatal development the testes of the domestic pig are remarkably active in steroidogenesis with a peak at 2-4 weeks after birth. Also, the range of steroid products seen at this stage is comparable to that shown by the mature boar. PMID- 8451913 TI - Evidence for the presence of fatty acid binding protein in avian granulosa cells. AB - The existence of fatty acid binding protein in chicken ovarian granulosa cells was investigated using a fluorescent assay based on the ability of cis-parinaric acid to fluoresce as a result of its interaction with proteins. Cytosolic fractions were prepared from granulosa cells obtained from the first (F1), second (F2), and third (F3) largest preovulatory follicles as well as from a pool of small yellow follicles of the chicken ovary, and each fraction was incubated with different concentrations of cis-parinaric acid. Total fluorescence increased (but fluorescence per milligram protein decreased) as the quantity of cytosolic protein from all follicle types was increased. Cis-parinaric acid fluorescence (which was also dose-dependent) was observed within 2 sec and increased with time reaching a plateau at about 10 sec. It was greater (p < 0.001) in the cytosolic fraction from F3 and small yellow follicle groups compared with F2 and F1 groups. Arachidonic, palmitic, oleic and stearic acids attenuated the fluorescence in dose-dependent fashion in cytosol from all follicle types presumably by displacing cis-parinaric acid from protein. Whereas arachidonic acid was most effective in suppressing fluorescence in fractions from F1 follicles, arachidonic acid lost part of its suppressive potency in fractions from F3 or small yellow follicles, and in these fractions palmitic acid was the most potent suppressor of fluorescence. These results indicate the existence of fatty acid binding protein like activity in chicken granulosa cells and demonstrate that its concentration is greatest in the immature follicles. This protein could play an important role in the transport of fatty acids within granulosa cells. PMID- 8451914 TI - Persistent neuropsychological deficits in cervical whiplash patients without direct headstrike. AB - Persistent cognitive and neurasthenic complaints can be the consequence of a cervical whiplash injury. In contrast to otoneurological and orthopedic reports, neuropsychological studies on whiplash patients are scarce. We report disturbances of information processing and memory functions in two patients with a pure cervical whiplash injury with demonstrated central otoneurological abnormalities, whereas there was no evidence of intellectual deterioration or focal cortical deficits. The results suggest that the cognitive disturbances and neurasthenic symptoms may be part of one syndrome which appears to manifest itself under conditions of time pressure and distraction. PMID- 8451916 TI - Cardiac conduction abnormalities during carbamazepine therapy for neuralgia following Guillain-Barre syndrome. AB - A 61-year-old man without previous medical history was admitted for Guillain Barre syndrome (GBS). Carbamazepine was prescribed on day 72 for dysesthesia occurring at the time of recovery. Subsequently, severe cardiac conduction disturbances (asystole, atrioventricular block) were observed and a permanent pacemaker had to be inserted. The possible relationship between carbamazepine therapy and cardiac side effects is discussed in this condition, as GBS itself is often complicated by cardiac arrhythmias. PMID- 8451915 TI - Sustained-release levodopa in parkinsonian patients with nocturnal disabilities. AB - It is now well recognized that poor quality of sleep, with fragmentation as the main characteristic, is a common problem in patients with Parkinson's disease. The effect of a sustained-release levodopa compound (Prolopa HBS) was assessed in a long-term (12 months) study of 15 patients presenting with distressing night time symptoms prolopa HBS was administered only ante noctem, without changing the usual daytime treatment. It appeared that alleviation of nighttime akinesia, reflected by the ability to turn around in bed, was perceived as the most worthwhile improvement. PMID- 8451917 TI - First year experience using the Fischer ZD-Neurosurgical Localizing Unit with particular reference to the development of PET-guided stereotactic biopsy. AB - Initial experience using the Fischer ZD-Neurosurgical Localizing Unit is reviewed. During the first year, 26 stereotactic procedures were performed in 25 patients. Twenty-two patients underwent imaging-guided stereotactic biopsy. Among them, 20 were included in the protocol we have developed for combined positron emission tomography (PET)- and computerized tomography (CT)-guided stereotactic biopsy. The technique is briefly described and preliminary results are reported. Most low-grade tumors were found in hypometabolic/hypodense areas, glioblastomas were all diagnosed in areas with increased FDG uptake and contrast enhancement on CT while data for anaplastic astrocytomas were heterogeneous. Some of the biopsic trajectories performed in areas were there was no increased FDG uptake or in areas with increased FDG uptake but without contrast enhancement on CT were non diagnostic. This never occurred in areas with both increased FDG uptake and contrast enhancement. Other stereotactic procedures performed include 2 catheter placement for drainage of cystic lesions, 3 stereotactically guided open neurosurgical procedures and 1 third ventriculostomy. Procedural objectives were accomplished in all cases. From our experience, we found stereotactic procedures using this system safe, accurate, easy to handle and allowing a wide range of applications. Because the system is designed to be readily used in conjunction with modern planar imaging techniques (i.e. CT and magnetic resonance imaging), it allowed us to develop a technique for PET-guided biopsy which might increase the diagnostic yield of stereotactic biopsy of intracranial neoplasms. PMID- 8451918 TI - Relation between the intra-articular temperature of the temporomandibular joint and the presence of neuropeptide Y-like immunoreactivity in the joint fluid. A clinical study. AB - Arthritic temporomandibular joints were examined for the joint fluid content of neuropeptide Y-like immunoreactivity (NPY-LI) and the intra-articular temperature at two separate sessions. Sixteen patients (23 joints) with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and unspecific polyarthritis or monarthritis were investigated in this study. The intra-articular temperature ranged between 35.6 and 37.5 degrees C. The concentration of NPY-LI ranged between 72.1 and 4466.0 pmol/l and was above the normal plasma level in all patients. The intra-articular temperature was negatively correlated with the joint fluid concentration of NPY-LI. Moreover, patients with low intra-articular temperature and high concentration of NPY-LI had a shorter duration of TMJ symptoms than those with high intra-articular temperature and low concentration of NPY-LI. PMID- 8451919 TI - Longitudinal relationship between incisal occlusion and incisal tooth wear. AB - The purpose of the study was to evaluate the longitudinal relationship between incisal wear of central incisors and the size of vertical overbite (OB) and horizontal overjet (OJ). Stone casts of 51 subjects were used for the determinations. Casts were obtained when the subjects were 15 and 27 years old. Statistical analysis was performed with the t test for paired samples, the chi square test of association. Pearson's product moment correlation coefficient, and Spearman's rank correlation coefficient. Both overbite and overjet diminished after 12 years, and incisal wear increased. It was concluded that increase in age, incisal wear, vertical overbite and incisal occlusion (OB/OJ) are clinical predictors of wear of maxillary and mandibular central incisors in adolescents. PMID- 8451920 TI - The Finnish Family Competence Study: the effects of living conditions on sucking habits in 3-year-old Finnish children and the association between these habits and dental occlusion. AB - Sucking habits and their connection with family background was investigated in 3 year-old Finnish children. The association between sucking habits and malocclusion was also studied. The study was based on a survey with stratified randomized cluster sampling, confidential questionnaires, and clinical dental examinations. Dummy (pacifier) use was often associated with a negligent attitude towards the child's toothbrushing. This may imply that these parents need more support, encouragement, and counseling from the well-baby clinic than others. Sucking habits were strongly associated with malocclusion. PMID- 8451921 TI - Intra- and inter-individual variation in salivary flow rate, buffer effect, lactobacilli, and mutans streptococci among 11- to 12-year-old schoolchildren. AB - Both intra- and inter-individual variation in salivary flow rate, buffer effect, and the levels of salivary mutans streptococci and lactobacilli were analyzed in 128 11-year-old children. The follow-up period was 9 months, with six saliva samplings done at regular intervals. Inter-individual variation was relatively large in paraffin-stimulated salivary flow rate: low (< 1.0 ml/min) and high (> or = 2.0 ml/min) flow rates were measured in 18% and 13% of the children, respectively. Intraindividual variation during the follow-up period was found in 63% of the boys and in 73% of the girls. The buffer effect stayed stable in all samplings in 59% of the boys and in 42% of the girls. Buffer effect was significantly (p < 0.001) lower in girls than in boys. Mutans streptococci were analyzed by a chair-side method (Strip mutans test) and by cultivation on mitis salivarius-bacitracin (MSB) agar plates. The results of the two methods correlated highly significantly (r = 0.79, p < 0.001). With the Strip mutans test no variation in test scores occurred in 49% of all subjects in all six samplings, whereas the respective percentage for MSB scores was only 19%. No variation in salivary lactobacilli occurred in only 18% of the subjects, and in 13% the intraindividual variation was as high as > or = 3 logs. These results show that in young teenagers with a developing dentition, simultaneous changes in behavioral, hormonal, and dietary factors make single-point measurements of salivary factors too unreliable for caries-diagnostic or predictive purposes. PMID- 8451922 TI - Desquamative effect of sodium lauryl sulfate on oral mucosa. A preliminary study. AB - Sodium lauryl sulfate (SLS) is the most commonly used detergent in dentifrices. The present study was concerned with the effect of SLS content of toothpastes on oral epithelial desquamation in an experimental model. Ten dental hygiene students participated in this double-blind cross-over study. Five dentifrices with different concentrations of SLS (ranging from 0.0% to 1.5%) were used in randomized order in the study. One centimeter of each test dentifrice was applied in a cap-splint, which covered both attached and non-attached oral mucosa of the upper jaw for 2 min twice daily. The test period for each experimental dentifrice was 4 days, followed by a 10-day rest period. The dentifrice without SLS did not result in any onward reaction, whereas the dentifrice containing 1.5% SLS provoked desquamation in 60% of the subjects. PMID- 8451923 TI - Leaching of organic additives from dentures in vivo. AB - Samples of saliva were collected from subjects with dentures. These samples were collected both before the dentures were replaced and 1 week after the subjects had received their new dentures. Dibutylphthalate and phenyl benzoate were detected in the saliva samples with a gas-chromatography and a gas chromatography/mass-spectrometry technique. We also quantified the dibutylphthalate in the saliva. In addition, in an in vitro study, we identified biphenyl leached from heat-cured denture base polymer plates. Our study suggests that subjects with dentures have higher contents of the above organic substances in saliva than subjects without dentures and that organic additives leach from new heat-cured dentures. PMID- 8451924 TI - Characteristics of patients with chronic idiopathic orofacial pain. A retrospective study. AB - Chronic orofacial pain without obvious pathologic findings is not uncommon and is a diagnostic problem. It is uncertain whether this type of pain is different from other chronic idiopathic pain conditions. Fifty-five patients referred to the Facial Pain Diagnostic Group at The Karolinska Institute, School of Dentistry at Huddinge University Hospital, Stockholm, were investigated retrospectively. There were 49 women and 6 men, ranging in age from 30 to 81 years, all with orofacial pain of more than 6 months' duration, which the patients considered to be of dental or paradental origin. Despite dental treatment aimed to relieve the pain, no permanent relief was observed. The results suggest that chronic idiopathic orofacial pain resembles other chronic idiopathic pain, and adequate diagnosis and treatment require not only dental but also medical competence. PMID- 8451925 TI - A new all-ceramic crown. A dense-sintered, high-purity alumina coping with porcelain. AB - A method of manufacturing an all-ceramic crown composed of a coping of dense sintered, high-purity alumina with dental porcelain is described. This method takes the sintering shrinkage of alumina into consideration and makes it possible to produce individual dental copings in dense-sintered, high-purity alumina, which is a biocompatible implant material. The alumina used has density, grain size, and flexural strength within the limits of the values required in ISO 6474 1981, 'Implants for surgery, ceramic materials based on alumina'. PMID- 8451926 TI - Influences of some background factors on the subjective need for dental implants in a Swedish population. AB - On the basis of a questionnaire sent to 3000 randomly sampled individuals aged 45 69 years and living in an average Swedish county (response rate, 79.4%), the influences of some demographic socioeconomic, and attitude variables on the subjective need for treatment with dental implants were studied in stepwise logistic regression models. The overall influence of these background factors was rather limited. Instead, the most important single factor seemed to be dental status. For the subjects wearing removable partial dentures, low education was significantly related to a low subjective need for implant treatment. For the totally edentulous group of subjects, low income was most significantly associated with a low subjective need for implant therapy. PMID- 8451927 TI - Low-back pain. Are orthopedic surgeons missing the boat? PMID- 8451928 TI - Arthrodesis of the first metatarsophalangeal joint in rheumatoid arthritis. Biodegradable rods and Kirschner-wires in 39 cases. AB - The first metatarsophalangeal joint was arthrodesed in 39 patients with rheumatoid arthritis. Fixation material was either biodegradable self-reinforced poly-L-lactide rods or Kirschner-wires. There were 3 clinical nonunions in the biodegradable group, and none in the K-wire group, and radiographic nonunion in 5 and 2 cases, respectively. The fixator had to be removed in 3 cases in the K-wire group. The biodegradable rods did not seem to be any better than K-wires. PMID- 8451929 TI - Lumbar vertebral growth plate displaced into the spinal canal. A case report of a 15-year-old boy. AB - Fracture of the lumbar cartilage plate is very uncommon. When the fragment protrudes into the spinal canal, the symptoms may mimic a protruded lumbar intervertebral disc. This may delay proper surgical treatment and may reduce the chance for neural tissue recovery. PMID- 8451930 TI - Thoracic disc herniation in spondyloepiphyseal dysplasia. A report on two cases. PMID- 8451931 TI - Acute compartment syndrome of the triceps. A case report. AB - A case of an acute compartment syndrome of the triceps muscle complicating a surgical neck fracture of the humerus is presented. Diagnosis was suspected because of pain with passive elbow flexion and pain out of proportion to the clinical situation. Diagnosis was confirmed with intracompartmental pressure measurements. An emergency fasciotomy was performed. The patient had an excellent result. PMID- 8451932 TI - Giant tuberculous abscess without primary focus identified. PMID- 8451933 TI - Spontaneous resorption of osteochondromatosis of the hip. A case report. PMID- 8451934 TI - MRI for diagnosis of metatarsal osteonecrosis. A case report. AB - A 12-year-old girl with forefoot pain for 1 month was suspected of having a metatarsal stress fracture. Plain radiographs were negative. MRI revealed the characteristic changes of osteonecrosis of the second metatarsal head. PMID- 8451935 TI - Intraoperative monitoring of spinal cord function. A review. PMID- 8451936 TI - Disc herniation in lumbar spondylolisthesis. Report of 3 symptomatic cases. AB - Because of its rarity, we present the case histories of three patients with a painful lumbar disc herniation in spondylolytic spondylolisthesis. The herniations were diagnosed by MRI and CT. Two of the herniations were confirmed at surgery, and one was treated conservatively. PMID- 8451937 TI - Spondylolysis after posterior decompression of the lumbar spine. 35 patients followed for 3-9 years. AB - Radiographs were examined in 35 patients who had had posterior decompression without fusion of the lumbar spine. Spondylolysis was found in 10 patients. Segmental range of motion, degree of vertebral slippage and width of decompression were analyzed by radiography. There was greater vertebral slippage after surgery in patients with postoperative spondylolysis than in those without spondylolysis. We conclude that excessive bony decompression may cause postoperative spondylolysis. PMID- 8451938 TI - Anterior fusion insufficient for scoliosis in myelomeningocele. 8 children 2-6 years after the Zielke operation. AB - 8 children with a mean age of 13 years with paralytic scoliosis due to myelomeningocele (MMC) were operated on according to Zielke with anterior fusion and instrumentation. There were no infections. All fusions healed. The postoperative mean follow-up was 4 years. The average correction of the primary curve was 62 degrees. In 5 cases proximal curve progression required reoperation; posterior fusion with Harrington rods was also done. Our last 2 patients, primarily operated on with both an anterior and posterior fusion, had no postoperative progression. Anterior fusion according to Zielke as the only procedure cannot be recommended in the treatment of severe paralytic scoliosis due to MMC. We advise a combined anterior and posterior approach in these cases. PMID- 8451939 TI - Prevalence of vertebral fractures in 85-year-olds. Radiographic examination of 462 subjects. AB - Radiographic examinations for the presence of vertebral fracture between Th4-L5 were performed in a random sample of 85-year-old women (n 304) and men (n 158) who participated in a longitudinal population study. A moderate vertebral fracture was defined as an anterior/posterior vertebral height ratio of 0.66 or less. A severe vertebral fracture was defined as a compression of vertebral height of more than 33 percent both at the anterior and posterior edges compared to the posterior edge of the adjacent vertebral body. The prevalence of vertebral fractures was 25 percent in women and 13 percent in men. The ratio between moderate and severe grades of vertebral fracture was 1.5 for women and 2.1 for men. The most common site for vertebral fracture was L1 in women and Th12 in men. Women with vertebral fracture at 85 years of age had more back pain. PMID- 8451940 TI - Location of transpedicular screws for fixation of the lower thoracic and lumbar spine. Computed tomography of 45 fracture cases. AB - Postoperative CT examinations of an unselected group of 45 patients with fractures of the thoracolumbar and lumbar spine including 1 patient with traumatically activated spondylolisthesis were analyzed for the location of the 200 screws, the angles of insertion, and the screw vs pedicle diameters. In all cases transpedicular systems had been used for fixation, i.e., the AO-Fixateur Interne in 28 patients, a combination of Teinturier plates and USI screws in 11 patients, and the VSP system in 7 patients. Using a standardized surgical technique and image intensification in 2 planes throughout, 92 percent of all pedicles were instrumented with acceptable deviations from the anatomic axes. Mismatches between the pedicle and the screw diameters were found in 3 instances, and 2 screws were placed in the transverse processes only. Canal encroachment in 13 patients did not impede neural structures. Slight perforation of the anterior cortex of the vertebral body was recorded in 3 percent of cases, but did not cause any complications. PMID- 8451941 TI - Decompression/stabilization of the metastatic spine. Cotrel-Dubousset Instrumentation in 50 patients. AB - 50 patients with metastatic disease of the spine underwent dorsal decompression and stabilization with the Cotrel-Dubousset-Instrumentation from 1987 to 1991. Indications for surgical treatment were neurologic deficit, spinal instability, and/or pain resistant to medical or radiation treatment. No external orthotics were used postoperatively. Pain was relieved dramatically in 45 patients. Among 25 patients suffering from neurologic deficit preoperatively, 13 improved, 15 remained unchanged, whereas 2 developed an incomplete, transient paraplegia. 15 (7) patients were alive after 1 (2) years. Postoperative complications were frequent, but there were only 2 failures of the stabilization device requiring reoperation. PMID- 8451942 TI - Discitis in childhood. 12-35-year follow-up of 35 patients. AB - We report a follow-up of 35 children, on average 17 years after they had intervertebral discitis. 15 patients still complained of backache. Flexion of the low back was normal in 32 patients, while extension was markedly restricted in 30. 26 patients had a block vertebra, and 28 patients had narrowing of the vertebral canal. Mode of treatment did not appear to affect the outcome. PMID- 8451944 TI - The effect of hyperbaric oxygenation on bone in spontaneously hypertensive rats. AB - We investigated whether hyperbaric oxygenation treatment can enhance osteogenesis in spontaneously hypertensive rats (SHRs). 8-week-old SHRs were exposed to hyperbaric oxygen for 6 weeks and were killed at 17 weeks of age. Wistar-Kyoto normal rats and untreated SHRs of the same age were used as controls. Radiographic measurements of cortical thickness and length of femora showed that these parameters increased in oxygen-treated SHRs; they became almost normal. Ash weight and ash, Ca and P content of L5 vertebras showed similar results. We conclude that high partial pressure oxygen has an effect on osteogenesis in SHRs. PMID- 8451943 TI - Lymph and blood supply of the human intervertebral disc. Cadaver study of correlations to discitis. AB - Immunohistochemical (antibodies against laminin) and histochemical methods (Ulex europaeus lectin, 5'-nucleotidase activity) were used to describe the vascular pattern of human intervertebral discs and the surrounding tissue at different ages. Blood and lymph vessels were found in the connective tissue outside the annulus in all age groups. In the annulus blood vessels and lymphatics were detected up to 20 years of age, in the cartilage end-plate blood vessels appeared up to 7 years of age (cartilage canals). In the nucleus pulposus neither blood nor lymph vessels could be seen at any age. The occurrence of blood and lymph vessels in growing intervertebral discs help us to understand childhood discitis without simultaneous affection of the vertebral body. PMID- 8451945 TI - Lipid extraction decreases the specific immunologic response to bone allografts in rabbits. AB - The immunologic response against frozen bank bone is generally considered to have no clinical importance. In a previous study, the bone formation rate in frozen allografts was measured at standardized conditions in the Bone Harvest Chamber. By defatting frozen allografts, the bone formation rate increased. In the present study, the effect of defatting was further investigated, as the specific immunologic influence was excluded by using autografts. Pairs of grafts were frozen and one graft in each pair was defatted with chloroform/methanol. With these autografts there was no difference in bone formation rate between defatted and non-defatted implants, measured with 99mTc-MDP. Combined with the previous experiments, the results indicate that the increased bone formation rate in defatted allografts is caused by the removal of specific cell surface antigens. Thus, the immunologic reaction to bank bone can be diminished by defatting. PMID- 8451946 TI - The role of hematoma and periosteal sealing for fracture healing in rats. AB - Bilateral closed femoral fractures were produced in two groups of rats. Reaming was made from the trochanteric area before fracture, and the fractures were stabilized by intramedullary pinning. In one (hematoma) group, both femurs were exposed subperiosteally at the midshaft prior to fracture. At one side, the hematoma was evacuated 30 min following fracture, at the other side the hematoma was left undisturbed. In the other (periosteal) group, the femur was exposed subperiosteally at one side, while the periosteum was left intact at the other side. The healing of the fractures was evaluated at 4 weeks. In the hematoma group, no differences were found in callus production, while bending moment and bending rigidity were greater at the side where the hematoma was not removed. No differences were found in fracture energy. In the periosteal group, marginal differences were found in the callus area. Bending moment, bending rigidity and fracture energy were greater at the side where the periosteum was left intact. A comparison of all four limbs, showed that the periosteal sealing was of particular importance for rapid healing. PMID- 8451947 TI - Clodronate reduces plate osteopenia in the rabbit. AB - An osteosynthesis with a four-hole AO/ASIF-DCP plate was performed on the right tibia of 40 rabbits. Clodronate (50 mg/kg s.c.) was given once a week, resulting in a mean bone concentration of 509 micrograms/g in 2 hours. Plate fixation caused a decrease in mean net cross-sectional area of compact cortical bone of 17 percent at 9 weeks and 46 percent at 18 weeks. This resulted from bone resorption in bone under the plate, from pronounced cavitation in the plated bone (about 5 percent of cortical bone area at 9 weeks and 15 percent at 18 weeks), and from the fact that the medullary space was increased by 15 percent at 18 weeks. The total cross-sectional area of the diaphysis was increased by 31 percent at 9 weeks and by 17 percent at 18 weeks. Clodronate treatment reduced cortical porosity to about half of the mean values in the placebo group. Clodronate increased both the calcium content in the retained bone and the cross-sectional area of compact cortical bone, but induced only an insignificant increase in the area of periosteal new bone. Clodronate treatment seems not to be contraindicated in conjunction with rigid osteosynthesis, and may even slow down the osteopenic response occurring under the rigid plate. PMID- 8451948 TI - Effects of instability on bone healing. Femoral osteotomies studied in rats. AB - Instability was induced in transversally osteotomized rat femora by means of intramedullary nails with various degrees of interlocking. Osteotomies that were stably pinned healed with less callus than those unstably pinned; no differences were found between rotational stable and unstable pinned osteotomies. Mechanical testing revealed that osteotomies treated by rotational stability and axial telescoping healed better than stably fixed and rotational unstable osteotomies. No differences were found between osteotomies treated by rotational instability and rigidily fixed fractures. We conclude that instability favors fracture healing as compared to rigidity. However, rotational instability in addition to telescoping impairs callus formation. PMID- 8451949 TI - Effect of local prostaglandin E2 on fracture callus in rabbits. AB - We investigated the effect of local infusion with prostaglandin E2 (PGE2) in doses of 0.0003 to 4.0 mg/hour per kg body weight for 6 weeks on a plated unilateral osteotomy in rabbits. PGE2 caused a dose-dependent stimulation of callus formation. Total bone mineral content increased, although the mineral content per volume of the callus was reduced. In another experiment, PGE2 was infused either in the first half or in the second half of the healing period. No effect of PGE2 infusion could be observed in the first half of the 6-week healing period, whereas PGE2 infusion during the second half caused callus stimulation. PMID- 8451950 TI - Effect of effusion on hip joint stability in the newborn. A postmortal study. AB - In a postmortal study we found that 1 mL fluid injected through the triradiate cartilage into the hip joint of a newborn child was enough to cause instability. This instability persisted even after aspiration of the fluid. The findings were confirmed by ultrasonography. PMID- 8451951 TI - Screw positions in femoral neck fractures. Comparison of two different screw positions in cadavers. AB - To evaluate the influence of different screw positions on the stability of fixation in femoral neck fractures, 30 cadaveric proximal femora were osteotomized and fixed with 2 cannulated screws. The proximal screw was placed either with a posterior cortical support in the femoral neck or centrally, supported only by cancellous bone. The distal screw rested on the femoral calcar. The specimens were tested in bending, using the force at 2 and 5 mm deflection at the osteotomy site and at fracture, as an expression of the stability of fixation. The test sequences were recorded on a x-y plotter and on videotape. Bone density measurements were made at the femoral neck, Ward's triangle, and the trochanter region. Our findings indicate that a posterior position with cortical support for the proximal screw, compared to a central screw position with only cancellous bone support, increases the stability of femoral neck fractures. PMID- 8451952 TI - Poor reproducibility of Evans' classification of the trochanteric fracture. Assessment of 4 observers in 52 cases. AB - The radiographs of trochanteric fractures in 52 consecutive patients were assessed by 4 observers, using the Evans' classification. The interobserver variation was large; only 23 of 52 radiographs were classified identically by all 4 observers. When only assessing stability, the 4 observers agreed in 34 of 52 radiographs. To assess the intraobserver variation, the same observers classified the same radiographs 6 weeks later. The first and second classifications were identical in 35-44 of 52 radiographs. PMID- 8451953 TI - Importance of sliding screw position in trochanteric fracture. 4 cases of secondary cervical fracture. PMID- 8451954 TI - The incidence of hip fracture in Uppsala County. Change of time trend in women. AB - The incidence of hip fracture in the population over 55 years in Uppsala County was calculated for the years 1980-1991. Specific incidences were calculated for each age, sex, and fracture type group. The time trend for the change in incidence was calculated for each group with linear regression using an exponential model. The overall incidence of hip fracture in both sexes over 55 years, standardized to the 1985 population, remained steady at 6/1000 during the study period. The incidence of cervical fractures in women showed a decrease in all age groups except over 85 years of age, where the incidence was constant. The corresponding incidence in men did not change over time. The incidence of trochanteric fracture increased in men 65-74 years of age and in women over 85 years of age. The incidence of trochanteric fracture in the rest of the age and sex groups remained unchanged. PMID- 8451955 TI - Bone density and geometry after locked intramedullary nailing. Computed tomography of 8 femoral fractures. AB - 8 patients with femoral shaft fracture treated with locked intramedullary (IM) nailing were examined by computed tomography (CT) a few days after nail removal. Cortical bone density, cortical thickness and geometrical shape of the fracture region were compared to those of the contralateral side. The cortical density was reduced by 23 percent at the mid-fracture level. However, at the same level the cortical thickness had increased by 47 percent, and the antero-posterior and medio-lateral diameters by 30 and 45 percent, respectively. We conclude that the fracture region of the femoral shaft had regained its mechanical properties at the time of nail removal. PMID- 8451956 TI - Bactericidal activity of gentamicin against S. aureus. In vitro study questions value of prolonged high concentrations. AB - Bactericidal activity of gentamicin against 4 strains of Staphylococcus aureus was investigated in vitro using Mueller-Hinton broth (MH) and surgical wound fluid (WF) as test media. 6 concentrations of gentamicin were tested ranging from 1-1024 micrograms/mL. During the first hour of incubation, there was a marked concentration-dependent kill rate, approximately 3 x 10(3) times in WF and 10(2) times in MH. After the first hour of incubation, the kill rate was independent of the concentration in both media. Our study questions the benefit of the prolonged and high wound concentrations of gentamicin obtained after application of gentamicin-containing PMMA. PMID- 8451957 TI - Fracture of the humeral capitellum fixed with absorbable polyglycolide pins. 1 year follow-up of 8 adults. AB - Absorbable self-reinforced polyglycolide pins were used for transarticular fixation of displaced Type I capitellar fracture in 8 adult women. An anatomical reduction was obtained, the fixation was stable, and function became good in all the cases. A sterile synovitis in one case was drained and subsided within 3 weeks, without further intervention. PMID- 8451958 TI - The natural course of lateral clavicle fracture. 15 (11-21) year follow-up of 110 cases. AB - 110 patients with non-operated on fracture of the lateral end of the clavicle were reviewed on an average 15 years after the injury. There were 73 undislocated Neer Type I fractures, 23 dislocated Type II fractures and 14 intraarticular Type III fractures. The patients' age at trauma was 36 (2-71) years. At follow-up 95 shoulders were asymptomatic. 15 shoulders had moderate pain and dysfunction and were rated fair; no patient had severe, residual shoulder disability. There were 10 nonunions, 8 of these asymptomatic. We conclude that fracture of the lateral end of the clavicle does not require operation. PMID- 8451959 TI - Embolization of spinal metastases reduces peroperative blood loss. 21 patients operated on for renal cell carcinoma. AB - We evaluated the peroperative blood loss in 21 patients who were treated with 29 operative procedures for thoracolumbar spinal renal cell carcinoma metastases. Embolization was undertaken prior to 11 operations. At posterior surgery the average blood loss was one third after embolization compared with when embolization had not been performed. The blood loss was also lower during anterior surgery, although this difference was smaller. We recommend that preoperative embolization should precede surgical treatment of spinal metastases of renal cell carcinoma where it can be anticipated that the operation will extend into the pathological tissue. PMID- 8451960 TI - A new approach to the subacromial space. Technique and 2-year results in 28 rotator-cuff repair cases. AB - We present a new approach to the subacromial space, consisting essentially of an osseous detachment of the deltoid muscle from the anterior and lateral rim of the acromion including the osseous origin of the coraco-acromial ligament. After acromioplasty and an eventual reconstruction of a torn rotator cuff, Kessler sutures provide stable transosseous repair of the deltoid muscle. This method generally allows immediate active shoulder motion. 25 of 28 patients with rotator cuff ruptures alone or in combination with an impingement syndrome had good results according to the UCLA-score 2 years postoperatively. No serious complications regarding the function of the deltoid muscle or any failure of the accompanying acromioplasty occurred. PMID- 8451961 TI - Early mobilization of operated on ankle fractures. Prospective, controlled study of 40 bimalleolar cases. AB - 40 patients with dislocated bimalleolar and trimalleolar ankle fractures took part in this randomized study. All ankles were operated on using cerclage, staples and pins. Active ankle movement with weight bearing in an orthosis was compared with active ankle movement without weight bearing using a dorsal splint. Stereophotogrammetric analysis showed small movements in the ankle mortise in both groups but conventional radiography revealed no fracture redislocation. The clinical results did not differ. This study was designed as the second part of a consecutive project. In the first part, early and late weight bearing in a cast without ankle movements was compared (Ahl et al. 1987b). In comparing the first and the second parts of the study, a small but significant increase in fracture instability was observed in the early motion group. No lasting superior clinical result was achieved by early ankle movement. After operation on dislocated bimalleolar ankle fractures, early postoperative weight bearing in a walking cast is recommended. PMID- 8451962 TI - Lumbosacral fusion with pedicular screw plating instrumentation. A 10-year follow up. PMID- 8451963 TI - Anterior lumbar interbody fusion. PMID- 8451964 TI - Posterior lumbar interbody fusion. A 2-year follow-up of 238 patients. PMID- 8451965 TI - Direct repair of spondylolysis. PMID- 8451966 TI - Percutaneous lumbar spine fusion. PMID- 8451967 TI - Meta-analysis of the results of lumbar spine fusion. PMID- 8451968 TI - Lumbar spine fusion--conclusions. PMID- 8451969 TI - Results of treatment of lumbar spine disorders. Effects of assessment techniques and confounding factors. PMID- 8451970 TI - Pathophysiology of disc degeneration. PMID- 8451971 TI - Evaluation of results in lumbar spine surgery. PMID- 8451972 TI - Evaluation of results in lumbar spine surgery. Clinical outcome measures- assessment of severity. PMID- 8451973 TI - Computerized follow-up after surgery for degenerative lumbar spine diseases. PMID- 8451974 TI - Radiology of the degenerative lumbar spine. PMID- 8451975 TI - The natural course of disc herniation. PMID- 8451976 TI - How patients react to low back pain. PMID- 8451977 TI - Physiotherapy. PMID- 8451978 TI - Chymopapain chemonucleolysis. PMID- 8451979 TI - Pathoanatomy of lumbar disc degeneration and stenosis. PMID- 8451980 TI - Automated percutaneous discectomy. Long-term clinical experience with the Nucleotome system. PMID- 8451981 TI - The lumbar microdiscectomy. PMID- 8451982 TI - Lasers in percutaneous disc surgery. Beneficial technology or gimmick? PMID- 8451983 TI - Results of discectomy compared with discectomy and fusion. PMID- 8451984 TI - Morphology in postdiscectomy problems. Importance of magnetic resonance imaging. PMID- 8451986 TI - Neurophysiology of cauda equina compression. PMID- 8451985 TI - Lumbar disc herniation--conclusions. PMID- 8451987 TI - Applied anatomy of the spine. PMID- 8451988 TI - Radiology of spinal stenosis. PMID- 8451989 TI - The diagnostic value of nerve root sheath infiltration. PMID- 8451990 TI - Central spinal stenosis. Classification and pathogenesis. PMID- 8451991 TI - The natural course of lumbar spinal stenosis. PMID- 8451992 TI - Patient-related factors predicting the outcome of decompressive surgery. PMID- 8451993 TI - Surgical aspects of central spinal stenosis. Indications and principles. PMID- 8451994 TI - Surgical aspects on lateral spinal stenosis. Indications and principles. AB - Lateral stenosis is a narrowing of the lateral recesses and/or foramina. It is most frequently caused by degeneration. Its clinical expression is variable and diagnosis requires imaging. Treatment is conservative, but should this fail, decompressive laminectomy and sometimes fusion is required. PMID- 8451995 TI - Vertebral slipping after decompression for spinal stenosis. PMID- 8451996 TI - Long-term results of surgery in lumbar stenosis. 8-year review of 64 patients. PMID- 8451997 TI - Spinal stenosis--conclusions. PMID- 8451998 TI - Spondylolysis and spondylolisthesis. AB - Lysis is common and its causes are mainly constitutional. Most of slipping has already occurred when the patient comes for consultation. A further progress is often caused by disc pathology. Neurological deficits are rare. A high-degree olisthesis and L4 location are risk factors for future back pain. Asymptomatic lysis with or without olisthesis should not be treated. A posterolateral fusion in situ without instrumentation gives good results in adolescents and young adults, whereas old patients benefit from instrumentation. Reduction cannot be recommended as a routine method. PMID- 8451999 TI - Postlaminectomy problems with reference to spinal fusion. AB - Absence of relief of sciatica after laminectomy is not an indication for fusion. Significant remaining low back pain with a distinct morphologic explanation sometimes may be considered an indication for fusion. Recurrent sciatica due to fibrosis is not relieved by fusion. Induced instability because of facetectomy responds well to fusion. Fusion for unspecific remaining complaints after decompressive surgery, not explained by distinct morphologic findings, should be avoided. PMID- 8452000 TI - Postfracture spinal pain. PMID- 8452001 TI - The use of orthoses in lumbar spine fusion. PMID- 8452002 TI - Diagnostic external fixation of the lumbar spine. PMID- 8452003 TI - Posterolateral uninstrumented fusion. PMID- 8452004 TI - Recent activities in otolaryngology -- head and neck surgery. Dedicated to Professor Tadami Kumazawa. PMID- 8452005 TI - Eustachian tube function tests and their diagnostic potential in normal and diseased ears. AB - We have summarized various methods for testing Eustachian tube function since the 1980's. There have been numerous contributions to our knowledge on Eustachian tube and middle ear functions, and the pathophysiology of disorders of the middle ear has been clarified. Understanding of the Eustachian tube function and controlling the Eustachian tube dysfunction are mandatory for adequate clinical management and for improvement of the prognosis. PMID- 8452006 TI - Subjective results of laser surgery for allergic rhinitis. AB - Inferior turbinates of 389 patients with perennial allergic rhinitis were vaporized by a defocused carbon dioxide (CO2) laser beam, using specially designed handpieces. This laser surgery can be done under local anesthesia as an outpatient procedure, with no pain or bleeding. One month after laser surgery, 78% of 389 patients had excellent or good results, while 21 had no improvement, subjectively. Seventy-two of 389 patients were followed for over 2 years, and 61 of the 72 had excellent or good results. Twenty-seven of the 72 cases need revaporization because of recurrence. Patients with relapse less than one year after surgery had little improvement in subjective symptoms, even after revaporization; while patients with relapse more than one year after surgery responded well, and long-term results were favorable. All things considered, laser surgery is an effective treatment for perennial allergic rhinitis. PMID- 8452007 TI - The usefulness of partial parotidectomy for benign parotid gland tumors. A retrospective study of 306 cases. AB - This retrospective study concerns benign parotid gland tumors in 306 Japanese patients who were treated by partial parotidectomy with preservation of the facial nerve. There were no recurrences in 112 with a pleomorphic adenoma in over a 5-year follow-up. Facial weakness and temporal paresis occurred in 18% of 232 patients and Frey's syndrome in 18% of 93 with longer than a 3-year follow-up. In comparison with reported results of lateral or superficial parotidectomy, partial parotidectomy with preservation of the facial nerve seems preferable for treatment of patients with a benign parotid gland tumor. PMID- 8452008 TI - Speech rehabilitation and complications of primary tracheoesophageal puncture. AB - Fifty-nine patients underwent tracheoesophageal puncture during laryngectomy, and a voice prosthesis was inserted into the tracheoesophageal fistula to enable alaryngeal speech. For 68% of the 59 patients, tracheoesophageal speech was feasible right after surgery, and postoperative complications occurred in 9 of these 59. The results show that primary tracheoesophageal puncture is advantageous for alaryngeal speech rehabilitation. Eighty-two percent of the 22 patients who survived more than 4 years after surgery continued with tracheoesophageal speech, and 16 complications occurred over a longer term in 13 of the 22 patients. Since 75% of these long-term complications could be overcome by surgical treatment, close observation of the tracheoesophageal fistula and adequate treatment are needed for patients with tracheoesophageal speech and making use of a voice prosthesis. PMID- 8452009 TI - Kinetics of epidermal growth factor in saliva. AB - Human epidermal growth factor (hEGF) stimulates the growth and differentiation of various tissues. We measured EGF levels in saliva (n = 128), urine (n = 94), and serum (n = 99) with radioimmunoassay in order to study the kinetics of hEGF in saliva of normal subjects and patients with oral disease. Salivary EGF levels showed an apparent diurnal rhythm related to the taking of meals. Urinary and serum EGF levels showed no obvious diurnal rhythm. There was no significant correlation between salivary and urinary EGF levels, nor between salivary and serum EGF levels. Salivary EGF levels were significantly lower in the younger group (0-9 years old, 3.06 +/- 0.32 ng/ml, p < 0.05) than in the elder group (10 79 years old, 4.78 +/- 3.5 ng/ml), but did not correlate with age in the elder group. There was no significant difference between males and females between EGF levels in saliva, urine or serum. The relative proportion of EGF levels in submandibular gland saliva, parotid saliva, and whole saliva was 1:6:4. The positive rate of immunohistochemical EGF showed no significant differences between submandibular gland, parotid gland, sublingual gland or minor salivary gland. Salivary EGF levels were markedly low in patients with oral inflammations (stomatitis aphthosa, or peritonsillar abscess) or head and neck tumors (squamous cell carcinoma of the tongue, oral cavity, hypopharynx or larynx). These findings may be significant pathophysiologically. Low salivary EGF levels may reduce the capacity of oral mucosal defense mechanisms to fight against injury by physiochemical agents. PMID- 8452010 TI - Head and neck reconstruction with microvascular tissue transfer and its surgical indications: our experiences. A review. AB - Microvascular tissue transfer has facilitated the primary closure of various complex defects after radical ablation of head and neck cancers. Recently, we have begun to use the forearm flap, osteocutaneous scapular flap, rectus abdominis myocutaneous flap, latissimus dorsi myocutaneous flap and jejunal autografts for reconstruction of the head and neck region following cancer ablation and have recognized further evidence of the versatility of free grafts. In this paper, we describe the results of 69 cases between 1987 and 1991 and the operative indication for microvascular tissue transfer in the head and neck region. PMID- 8452011 TI - Thyroid follicle transplantation by percutaneous injection. AB - We previously reported on the isolation of thyroid follicles from thyroid tissue and their acceptance after allogeneic transplantation under the renal capsule with laparotomy in mice. In the present study, we introduced a new method of autologous transplantation of thyroid follicles accepted in the hosts after percutaneous injection into the spleen or into fat tissue in the peritoneal cavity without laparotomy in rats. This method of thyroid transplantation by a single injection, which induces little stress in the host, is applicable to autologous and allogeneic transplantations and may release patients from the burden of daily life-long administration of thyroxine. PMID- 8452012 TI - Inhibition of head and neck tumor cell colony growth by lymphokine activated killer cells. AB - The antiproliferative effect of lymphokine activated killer (LAK) cells on head and neck tumor cells has not previously been elucidated. We studied the inhibitory effects of recombinant interleukin-2 activated lymphocytes on tumor colony formation in semisolid agar, using head and neck tumor cells prepared from established tumor cell lines (K562, HT29, HLaC78) and xenografted head and neck squamous cell carcinomas on nude mice (XKN, XLL, XFL, XKF). LAK cells demonstrated a significant inhibitory effect on colony formation. The effects of LAK cells on cultured tumor cell lines were evaluated in a dose dependent manner using effector: target ratios. In addition, the colony formation of tumor cells derived from xenografted nude mouse was inhibited by LAK cells. These results suggest that LAK cells generate an antiproliferative effect on head and neck tumor cells. PMID- 8452013 TI - Tubotympanoplasty. AB - Prognostic value of the Eustachian tube function test remains controversial. To prevent ear drum adhesion or the recurrence of cholesteatoma it is important to select cases with severe organic obstruction of the Eustachian tube and to use surgical procedures to restore function. We summarize here the indications and the surgical procedure for organic obstruction of the Eustachian tube, especially in the region of the tympanic orifice. Adequate preoperative evaluation of Eustachian tube function and pertinent surgical procedures will pave the way for a better prognosis for patients subjected to ear surgery. PMID- 8452014 TI - Establishment of a cisplatin-resistant KB cell line and its characterization. AB - A KB cell line resistant to cisplatin (KB-rc cell) was successfully established by exposing KB cells to a gradually increasing dose of cisplatin in vitro. The concentration of cisplatin required for 50% inhibition of KB-rc cell proliferation was 1.0 micrograms/ml, while that of KB cells was 0.5 micrograms/ml. Studies of KB-rc cell kinetics after treatment with cisplatin, using flow cytometry, showed that the G2M phase block was inhibited on day 3, and that G0G1 phase cells started to increase on day 5. Therefore, cisplatin resistance is related to inhibition of the G2M phase block. The decrease of KB-rc cell viability with cisplatin was accelerated by the addition of a Ca antagonist (verapamil) and S phase cells increased on day 3. Verapamil may therefore be useful for enhancement of the effect generated by cisplatin on cisplatin resistant tumor cells. PMID- 8452015 TI - Chemosensitivity testing of human mouth carcinoma cell line. AB - The chemosensitivity of KB cells derived from oral epidermal carcinoma to various antitumor agents was analyzed using the MTT[3-(4,5-dimethyl-2-thiazoyl)-2,5 diphenyl-2H tetrazolium bromide] assay. Optical density (OD) for MTT assay was measured with dual wavelengths. The chemosensitivity of the drugs was evaluated by the 50% OD (OD50) of each drug concentration in the control group. Five platinum (Pt) drugs and 3 anthracycline (AC) drugs were used in this study. The chemosensitivity differed among the 5 Pt drugs. No significant difference was observed among the 3 AC drugs. A linear increase in OD corresponding to an increase in number of cells was observed. When 0.1 M sodium succinate (S.S.) was added to 0.4% MTT, the sensitivity increased five-fold compared to the control group without S.S. The MTT assay is a precise, rapid, easy and inexpensive experimental system useful for evaluation of antitumor drug sensitivity on tumor cell lines. PMID- 8452016 TI - Identification of rat brainstem sites with neuronal Fos protein induced by acoustic stimulation with pure tones. AB - Induction of Fos, a proto-oncogene c-fos protein product, was immunohistochemically examined in the rat brainstem by using pure tone stimuli (0.25 kHz, 4kHz and 8 kHz) at 60 and 80 dB sound pressure levels for 30 min. In comparison with non-stimulated control rats, the brainstem of sound-stimulated rats exhibited distinct Fos-labeled neuronal cell nuclei in i) the ascending auditory nuclei, ii) the brainstem sites which receive afferents from the auditory nuclei, i.e. the pretectum and rostroventrolateral reticular nucleus, iii) the parvocellular part of the ventral lateral geniculate nucleus, lateral reticular nucleus, ventral border region of the spinal trigeminal nucleus, and the medial vestibular and spinal vestibular nuclei, all of which lack established auditory projections, and iv) the brainstem sites where some Fos-labeled neurons were present in controls. Sound stimulation at 80 dB led to widespread Fos labeling in all these sites. Sound stimulation at 60 dB caused a decrease in number of positive cells in the brainstem sites and yielded a tone-dependent subregional distribution pattern in the dorsal cochlear nucleus and central nucleus of the inferior colliculus. PMID- 8452017 TI - A possible masking effect of tinnitus. Evaluation of CNV audiometry. AB - To determine whether tinnitus has a masking effect similar to that of general external sounds, the hearing threshold shift when the tinnitus was changed by intravenous administration of lidocaine was measured by contingent negative variation (CNV) audiometry. In a preliminary study, the reliability of CNV audiometry was evaluated in 12 patients with tinnitus. The reproducibility of CNV audiometry was confirmed, based on repeated measurements of CNV audiometry at the tinnitus frequency. The threshold difference between CNV audiometry and pure tone audiometry was -0.76 +/- 1.35 dB, and a high statistical correlation between the threshold of CNV audiometry and pure tone audiometry was evident. The CNV threshold shift at tinnitus frequency after lidocaine injection was measured in 89 ears. In the tinnitus-decreased group, the CNV threshold decreased (4-6 dB) in 22% of cases; however, in the tinnitus-unchanged group, the CNV threshold was little changed. These findings suggest that tinnitus may have a masking effect as is the case with external sounds. PMID- 8452018 TI - Meniere's disease and autoimmunity: clinical study and survey. AB - In order to clarify whether autoimmune mechanisms form part of the etiopathogenesis of Meniere's disease, sera and endolymphatic sac tissues from 30 patients with Meniere's disease were analyzed according to the clinical criteria for autoimmune diseases stated by Mackay & Burnet. Several cases showed hyper gamma-globulinemia, antibody elevation to Type II collagen in the serum and endolymph, positive staining to immunoglobulins and C3 or infiltration of immuno competent cells in the endolymphatic sac, good response to prednisolone and combination with systemic immune disorders. Other examinations showed a significant elevation of OKT 4/8 ratio and a decrease of OKT8-positive cells, and elevated levels of circulating immune complex and antiviral antibody titers. It is suggested that certain cases of Meniere's disease may have an altered immunological background, which may be attributed to an autoimmune mechanism dependent on humoral and/or cellular responses. PMID- 8452019 TI - Surgical anatomy for infralabyrinthine approach to the internal auditory canal. AB - Surgical anatomy for infralabyrinthine approach to the internal auditory canal was evaluated using human temporal bone in order to understand advantages and disadvantages of this approach. The procedure is extracranial without any damage of labyrinth. Lateral exposure of the internal auditory canal allows for easy separation of the cochlear and vestibular nerves. There are some potential problems of little importance stemming from anatomical variations, such as high jugular bulb, forward positioned sigmoid sinus and poor pneumatization of the infralabyrinthine space. This approach offers access to the eighth cranial nerve with minimal risk and morbidity. PMID- 8452020 TI - Effects of acetazolamide on acid-base balance in the endolymphatic sac of the guinea pig. AB - The effects of acetazolamide, a carbonic anhydrase inhibitor, on acid-base parameters in the endolymphatic sac of the guinea pig were investigated using ion selective microelectrodes. Bicarbonate concentration was reduced and pH shifted to being acidic immediately after administration of acetazolamide. Chloride concentration in the endolymphatic sac increased after carbonic anhydrase inhibition. These findings provide evidence of an active function of carbonic anhydrase in the endolymphatic sac and suggest that carbonic anhydrase activity is involved in the formation of endolymphatic sac fluid. PMID- 8452021 TI - MR imaging of vascular compression in hemifacial spasm. AB - Hemifacial spasm is related to vascular compression of the root entry zone of the facial nerve at the brainstem by elongated tortuous vessels of the vertebrobasilar arterial system. In this study, we performed MR imaging in 16 patients with hemifacial spasm and investigated the vascular structures in bilateral-cerebellopontine angles and the relationship of each vessel to the root entry zone of the facial nerve. MR examination was performed with a 0.5 tesla MRI system, and MR angiography (3D time-of-flight) was obtained. Of 15 patients in whom both the nerve and vessels were clearly visible and could be observed to contact each other at the root entry zone, in 11 the tortuous artery could be identified by name. In only 1 patient was the contact between the nerve and vessel indeterminate, due to nonvisualization of the vessel around the facial nerve at its root entry zone. These findings suggest that MRI is a useful screening method in the preoperative assessment of hemifacial spasm. PMID- 8452022 TI - Enhanced MRI in patients with Ramsay-Hunt's syndrome. AB - Enhanced MRI was performed in 14 patients with Ramsay-Hunt's syndrome to investigate the pathogenesis of this syndrome. All MRI studies were performed on a 0.5T superconductivity MRI system using a head coil with Gd-DTPA. Enhancement was observed in the areas of the distal internal auditory canal and labyrinthine segment in many patients, and was especially prominent in patients suffering from vertigo, tinnitus, and hearing loss. In some patients it involved not only the facial nerve of the internal auditory canal but also the cochlear nerve and vestibular nerves. Since histological changes of the facial nerve in patients with Ramsay-Hunt's syndrome are assumed to occur in the distal internal auditory canal and labyrinthine segment, which is more proximal than the geniculate ganglion, and the possibility is suggested that inflammation may spread to the vestibular and cochlear nerve via the internal auditory canal. PMID- 8452023 TI - Active opening function of the human eustachian tube: comparison between sonotubometry and pressure equilibration test. AB - Sonotubometry and pressure equilibration test are representative test methods to evaluate the active opening capacity of the Eustachian tube. We applied these tests to 72 ears with otitis media with effusion and 21 ears with chronic otitis media. In 73 ears, both tests showed identical results (11 ears with good active function and 62 ears with poor function). Twenty ears showed good active opening by sonotubometry despite inability to relieve applied negative pressure by swallowing. This inconsistency is believed to result from a too short duration of the tubal opening, by which sound is transmitted through the Eustachian tube, without pressure change in the middle ear cavity. We propose that sonotubometry is a suitable method of detecting impairment of the tubal active opening function, but that a good result by sonotubometry does not always indicate a satisfactory pressure equilibration capacity of the Eustachian tube. PMID- 8452024 TI - Otitis media with effusion and eustachian tube dysfunction in adults and children. AB - Eustachian tube (ET) function was studied in 162 ears with otitis media with effusion (OME) and chronic otitis media (COM), using tubo-tympanoaerodynamic graphy, patency and pressure equilibration test in the inflation-deflation test. Severe impairment of active opening function was found in both OME children and adults compared with that of COM patients. This impairment in active opening was thought to result from functional obstruction of the ET in 71.8% of OME children and 51.8% of OME adults. However, 45.6% of OME adults had an organic obstruction while such was present only in 28.2% of OME children. We deduce from this study that impaired active opening function of the ET in both OME children and adults is the result of functional obstruction rather than organic obstruction, but organic obstruction is considered to be related to the pathogenesis of OME in adults. PMID- 8452025 TI - Animal model of otitis media with effusion. AB - A rat model of otitis media with effusion (OME) was developed by intratympanic injection of E. coli endotoxin and section of the third branch of the trigeminal nerve (V3). The period of fluid retention induced by the endotoxin was prolonged for 5 days or longer, in cases when tubal function was impaired by cutting of V3. Three Eustachian tube function tests (patency test of inflation-deflation tests, forced response test and negative pressure test) were carried out before and after the endotoxin inoculation and V3 sectioning. At 4 days after these procedures, passive opening pressure (Po), closing pressure (Pc) and tubal resistance (R2) were significantly lowered. The negative pressure test showed impaired capacity of active opening. This model of Eustachian tube dysfunction is considered to reveal functional obstruction, a condition similar to that of clinical cases of OME. The study shows that both inflammation in the middle ear and tubal dysfunction, such as functional obstruction, are factors in the development and prolongation of OME. PMID- 8452026 TI - Culture of middle ear epithelium: a review. AB - We discuss several techniques of culturing middle ear epithelium from several species, which was formerly difficult but is now possible because of recent advances in culture methods. The three main methods of initiating a culture are organ culture, primary explant culture, and cell culture. Although each method has both advantages and disadvantages, investigators can choose the method most suitable to their purpose. A few researchers, including ourselves, have succeeded in obtaining serial culture of middle ear epithelium. Using 3T3 feeder layer technique or conditioned medium enabled us to develop a fibroblast-free cultured middle ear epithelium. The availability of cultured middle ear epithelium provides a potential tool in future middle ear research. PMID- 8452027 TI - Regional blood flow volume in the eustachian tube. AB - Measurements of regional blood flow around the pharyngeal orifice of the Eustachian tube were carried out after topical administration of various inflammatory mediators in 14 mongrel dogs by the hydrogen clearance method. Histamine and platelet-activating factor (PAF) resulted in a significant alteration of blood flow volume. Histamine was found to induce a dose-response related increase, whereas blood flow volume tended to decrease in each concentration range in the series of PAF administration. There was no significant difference in blood flow between topical application of leukotriene C4 and leukotriene D4. It is likely that in upper respiratory tract inflammation, such as in otitis media and in nasal allergy, activated histamine and PAF affect the microcirculation of the tubal orifice. These results suggest that disturbance of the microcirculatory system in the Eustachian tube mucosa could be involved in the pathogenesis of chronic otitis media with effusion. PMID- 8452028 TI - The determination of phospholipids in middle ear effusion from experimental otitis media in the chinchilla. AB - Phospholipid types were clarified both in eustachian tube secretion (ETS) and middle ear effusions (MEEs) from chinchilla middle ear. ETS was obtained from normal healthy animals and from animals with experimentally induced purulent otitis media (POM). MEE was obtained from experimentally induced serous and purulent otitis media (SOM and POM). In normal ETS, phosphatidylcholine (36.4%) was predominant followed by phosphatidylethanolamine (30.6%), sphingomyelin (18.0%), phosphatidylinositol (7.2%), phosphatidylglycerol (8.8%) and phosphatidylserine (2.5%). A significant loss of phosphatidylcholine was observed in ETS and MEE from experimentally induced otitis media. These findings suggest that both POM and SOM might be caused by a relative decrease of phospholipids, which is a major component of surfactants. Furthermore, the analysis of phospholipids in MEE may yield baseline information necessary to specify the factors responsible for chronicity or the tendency of recurrence of otitis media. PMID- 8452029 TI - Functional disturbances of the autonomic nerve in nasal hyperreactivity: an up date review. AB - During the 1980s, our view of airway hypersensitivity was altered significantly. Advances in biochemical techniques revealed involvement of several nonspecific events in nasal hyperreactivity: Autonomic dysfunction involving primary and/or secondary receptor disorders, epithelial damage by cytotoxic proteins in eosinophil, which is stimulated by inflammatory mediators, and an axonal reflex of sensory C fibers. Since 1983, we have neurobiochemically investigated the autonomic nerve dysfunction in the nasal mucosa of patients with nasal allergy and guinea pigs with experimentally-induced nasal hypersensitivity. We propose the following mechanisms as potential contributors to the disturbance of the beta receptor function in airway hyperreactivity: i) Down-regulation caused by excess endogenous norepinephrine stimulation, ii) down-regulation and uncoupling to adenylate cyclase, produced by the inflammatory mediator-induced activation of protein kinase C, iii) the action of beta receptor inhibitory factor, presumably anti beta receptor autoantibodies, and iv) dysfunction of beta receptor kinase, which is known to cause short-term desensitization of beta receptors after exposure to beta agonists. This review provides the anatomical and neurobiochemical background for the autonomic regulation and dysfunction in the nose. We also introduce our series of experiments and the above updated hypotheses of how functional disturbances of the autonomic nerve in the nasal mucosa may occur. PMID- 8452030 TI - 2-Iodoxybenzoate as a titrant for the determination of some pharmaceutically important thiol compounds. AB - A simple and reliable method was developed for the determination of five pharmaceutical compounds containing thiol group; namely: N-acetylcysteine, D penicillamine, 6-mercaptopurine, captopril and thioguanine. The method is based on the use of 2-iodoxybenzoate as a titrant in acid medium. The detection of the end point is accomplished potentiometrically, using platinum/calomel electrode combination. For all the studied compounds, the stoichiometry of the reaction was found to be 2:3 suggesting that, the thiol group is oxidised to the corresponding sulphonic acid. This finding was confirmed through TLC study of the reaction products. The proposed method was successfully applied to the determination of the studied compounds in dosage forms and the results were in good agreement with those given using the official methods. PMID- 8452031 TI - Assay of certain oral contraceptive formulations by gas chromatography-mass spectrometry-selected ion monitoring. AB - The combined technique of gas chromatography--mass spectrometry--selected ion monitoring (GC-MS-SIM) has been employed for the nanogram level determination of ethinyloestradiol, mestranol, norgestrel and norethisterone in various oral contraceptive formulations. Steroids were assayed as their DMES-or methoxime DMES ether derivatives in the presence of ethisterone as the internal standard. The method is accurate, specific and suitable for single tablet assay. PMID- 8452032 TI - Application of ternary complexes in pharmaceutical analysis. IV- Spectrophotometric determination of iron (II) in anti-anaemic formulations, using as chelating ligands in micellar medium three newly developed hydrazones. AB - The preparation, structural and physicochemical characterisation of three new hydrazones of isoniazid with 2,3-dihydroxy-,3,4-dihydroxy- and 2,3,4-tri hydroxybenzaldehyde are described. The formation of binary chelates of iron(III) with these hydrazones and ternary complexes with the hydrazones and various surfactants were studied including the optimization of the experimental conditions. The new reagents were successfully used for the spectrophotometric determination of iron(II) in anti-anaemic formulations after its oxidation with hydrogen peroxide to iron(III). The statistical comparison of the results obtained with the new reagents and with the classical o-phenanthroline method is presented. PMID- 8452033 TI - Chromogen-substrate assay--as a tool for monitoring a new thrombin inhibitor. AB - The N-methyl-D-phenylalanyl-L-prolyl-arginine-aldehyde sulfate tripeptide aldehyde (GYKI-14766) is an anticoagulant with specific thrombin inhibitor action. The molecule proved to be effective in rabbits, rats and dogs upon i.v. administration. Chromogen-substrate assay was developed for monitoring of biologically active tripeptide-inhibitor GYKI-14766 in plasma. The assay based on the inhibition of the active center of the thrombin enzyme, so it is suitable also for the assay of all those active metabolites which inhibit thrombin by a mechanism similar to the active parent compound. The chromogen substrate assay was performed in a range of 0.625-10 micrograms/ml GYKI-14766 in dog plasma. The assay was employed in pharmacokinetic study in dogs after i.v. administration. The data obtained in the chromogen-substrate assay were analyzed according to a one-compartment model. The major parameters of the plasma level studies were: D/V = 8.6 microEqv/ml t1/2 = 30.8 min AUC = 380 min microEqv/ml. PMID- 8452034 TI - [Anti-edematous effects of cinnarizine]. AB - Experiments carried out with male mice (28-32 g) of CFLP strain have shown that cinnarizine significantly inhibits the extents of ear oedema induced by croton oil or capsaicin. In rats of Wistar strain, oedema was induced in the hind paw by subplantar injection of carrageenin, and simultaneously by the application of croton oil to the inner surface on the ear. Preliminary cinnarizine treatment inhibited the development of both types of oedema, to statistically significant extent. PMID- 8452035 TI - Addition of purified orosomucoid preserves the glomerular permeability for albumin in isolated perfused rat kidneys. AB - The serum protein, orosomucoid has been shown to be essential for the maintenance of normal capillary permeability in several different organs, including the kidney. Thus, the clearance of albumin was found to be almost fivefold higher in the absence of orosomucoid in a previous study on isolated rat kidneys, perfused with either of two commercially available human albumin solutions of similar composition, but differing in their content of orosomucoid (0.21 g l-1 vs. < 0.005 g l-1). The following experiments were performed in order to verify the hypothesis that this effect on glomerular permselectivity was due to orosomucoid per se and not to other ingredients in the two solutions. Both kidneys of 12 rats were isolated and perfused with identical albumin solutions without orosomucoid, but with the addition of purified orosomucoid (0.25 g l-1) to one of the kidneys. No significant differences in vascular resistance, urine flow or glomerular filtration rate (GFR), which was found to be 27 +/- 2 ml min-1 100 g-1, were observed between the two groups of kidneys. The fractional clearance of albumin (theta) was initially similar for both kidneys (0.0022 +/- 0.0002). In the absence of orosomucoid, theta gradually increased to 0.0076 +/- 0.0013 after 1 h of perfusion compared to 0.0040 +/- 0.0006 for the kidneys with orosomucoid added to the perfusate (P < 0.001, n = 12). We conclude that the plasma glycoprotein orosomucoid indeed plays an important role in regulating the dynamic properties of the glomerular capillary wall by reducing the permeability towards macromolecules such as albumin. PMID- 8452036 TI - Effects of exercise training on the biosynthesis of prostacyclin and thromboxane in rats. AB - The effects of exercise training on eicosanoid levels were studied in male Wistar rats. One-month-old rats were trained on a drum exerciser at an intensity of around 70% of maximal oxygen consumption for 10 weeks (60 min day-1, 5 days week 1) after familiarization. Some animals of the same age did not exercise and served as a control. Two days after training, several blood vessels, including thoracic aortae, inferior vena cavae, external iliac arteries, external iliac veins, common carotid arteries and jugular veins, were excised and incubated for 10 min. Basal release of prostacyclin from these vessels was determined using [125I]radio-immunoassay (RIA) of 6-keto-PGF1 alpha. The levels of plasma prostacyclin and urinary metabolites of prostacyclin and thromboxane were also determined by RIA. Our results showed that trained animals had lower body weight and urine 11-dehydro-thromboxane B2 levels than the controls (P < 0.001 and P < 0.05, respectively). In contrast, urinary 2,3-dinor-6-keto-PGF1 alpha level was elevated after training (P < 0.05). Nonetheless, prostacyclin levels in plasma and from various dissected vessel segments, except thoracic aorta, did not change significantly after training. These findings suggest that exercise training may affect endogenous eicosanoid levels by increasing the basal release of prostacyclin and reducing the basal thromboxane level. PMID- 8452038 TI - Changes in the ovarian intermediate filament desmin during the luteal phase of the adult pseudopregnant rat. AB - The occurrence of the intermediate filament desmin in ovary and corpus luteum of pseudopregnant rats was studied using Western blot analysis and immunohistochemistry. The luteal phase was induced by mating with vasectomized male rats and ovaries were studied after 6, 11 and 19 days. The findings from the Western blot analysis showed that desmin was present in the corpus luteum. Immunohistochemical localization of desmin showed two types of localization in the corpus luteum. The arteries around the corpus luteum, as well as arteries elsewhere in the ovary, had a high content of desmin in their muscle layer. Dispersed in the corpus luteum was an immunohistochemical staining of desmin that was localized mainly adjacent to the luteal cells. In the other part of the ovary a weak staining was registered in the theca layer, no staining in the granulosa layer and a streaky staining in the hilar region of the ovary. Desmin filaments are found in muscle cells of all types, including vascular smooth muscle cells. Probably, all desmin in the ovary is localized to smooth muscle cells with the possible exception of the corpus luteum where very few muscle cells have been identified. Localization to other vascular cells as endothelial is possible. In this study we found an increase in desmin content in the corpus luteum after day 6. If desmin is related to vascular resistance, our finding is consistent with the decrease in blood flow that occurs after day 6. PMID- 8452037 TI - Biosynthesis of 12(S)-hydroxyeicosatetraenoic acid by bovine corneal epithelium. AB - Microsomes of bovine corneal epithelium metabolized [14C]arachidonic acid extensively to [14C]12-hydroxyeicosatetraenoic acid. The biosynthesis was not stimulated by exogenous NADPH and it could be inhibited by over 90% with two lipoxygenase inhibitors, esculetin and eicosatetraynoic acid. Chiral phase high performance liquid chromatography showed that 12-HETE consisted of the 12S enantiomer. The results indicate biosynthesis by 12S-lipoxygenase of bovine corneal epithelium rather than by cytochrome P450. PMID- 8452039 TI - Endothelin contracts human uterine myometrium by a partly dihydropyridine sensitive mechanism. AB - The effect of endothelin (ET), a recently discovered 21-amino-acid polypeptide with powerful vasoconstrictor properties, was examined on human uterine myometrial strips in vitro. ET dose-dependently (10(-11)-10(-7) M) increased the contractile force (monitored as contraction amplitude) of the myometrium with significant effects at 10(-8) and 10(-7) M. ET (10(-8) M and up) also increased the basal tone of the myometrium. The calcium channel blocking agents nifedipine (10(-7) M) and diltiazem (10(-6) M) both inhibited the spontaneous tonic contractions of the myometrium. When ET was given in the presence of nifedipine, the tonic contractions were further inhibited, whereas the ET-induced increase in basal tone remained. The same result was obtained with diltiazem (10(-6) M). The results indicate that the contractility of human myometrium may be modulated by ET, and that the effects of ET on the human myometrium are only partly mediated by dihydropyridine-sensitive calcium channels. PMID- 8452040 TI - Capillary diffusion capacity for Cr-EDTA and cyanocobalamine in spontaneously beating rat hearts. AB - In order to obtain a functional estimate of the diffusional capacity of the myocardial capillary bed, the permeability surface area product (PS) for Cr-EDTA (mol. wt = 341) and cyanocobalamine (vitamin B12, mol. wt = 135) was determined in spontaneously beating Langendorff-perfused rat hearts over a wide range of coronary flow rates (700-3000 ml min-1 100 g-1). PS was determined by a single injection, colorimetric indicator dilution technique, allowing multiple, rapid and accurate determinations to be made in the same heart. During maximal vasodilation with nitroprusside Na PS averaged 535 +/- 33 and 220 +/- 22 ml min-1 100 g-1 for Cr-EDTA and vitamin B12 respectively at the highest flow (2917 +/- 74 ml min-1 100 g-1). The vasculature of the heart was found to be highly heterogeneous, since PS increased with flow and there were marked variations of extraction over transit times. A functional estimate of 'equivalent pore radius' was obtained from the ratio PSCr-EDTA/PSB12, which was 2.61 +/- 0.15 demonstrating a marked restriction to diffusion corresponding to a pore radius of 51 (41-75) A. This value is similar to that from skeletal muscle determined by the same method while PS-values are 40-45 times higher in the heart (Haraldsson & Rippe 1986). Taken together with morphological estimations of capillary surface area and endothelial path depth, these data indicate a 3-fold increase in the density of pores available for diffusion in the myocardium, compared to skeletal muscle. PMID- 8452042 TI - Modification of regional myocardial performance caused by blood withdrawal and infusion in acute ischaemic canine heart. AB - The effect of changes in preload on regional myocardial motion in acute ischaemia was examined by miniature ultrasonic gauges after left anterior descending coronary artery occlusion in eight open chest dogs with the pericardium preserved. Left ventricular end-diastolic pressure was varied by blood withdrawal and infusion. When preload changed, isovolumetric shortening in the non-ischaemic region was inversely related to that in the ischaemic region. When preload decreased, stroke volume decreased and was accompanied by a decrease in end diastolic length and ejection shortening in the non-ischaemic region together with an increase in isovolumetric bulging in the ischaemic region. When preload increased, these variables changed in opposite directions. These results indicate that in acute ischaemia: (1) changes in isovolumetric shortening in the non ischaemic and ischaemic regions were related with each other when the level of volume expansion varied, and suggest that; (2) stroke volume is affected by end diastolic length, ejection shortening in the non-ischaemic region and isovolumetric bulging in the ischemic region. PMID- 8452041 TI - Changes in myocardial capillary diffusion capacity during infusion of vasoactive drugs. AB - The present study investigated how variations in coronary vascular resistance and metabolic demand affected myocardial capillary diffusion capacity. Hearts from Wistar rats were perfused with Krebs-Henseleit-albumin buffer in a Langendorff preparation, where heart rate (HR), contractility (dP/dtmax) and myocardial oxygen consumption (MVO2) were recorded continuously. Myocardial capillary diffusion capacity was measured as the permeability surface area product (PS) for Cr-EDTA and vitamin B12 by the single injection colorimetric indicator dilution method. After base-line recordings without drugs, angiotensin II+Arginine vasopressin was infused, which increased coronary vascular resistance by 90%, stimulated HR by 11%, decreased dP/dtmax by 21% and reduced MVO2 by 4%. PSCr-EDTA and PSB12 decreased by 24 and 27%, respectively, leaving the ratio PSCr EDTA/PSB12 unchanged indicating unaltered capillary permeability. Moreover, the reductions in MVO2 and PS correlated significantly. During vasodilation: (1) nitroprusside-NA stimulated HR by 7% and decreased dP/dtmax by 14%; (2) adenosine reduced dP/dtmax by 37% and decreased MVO2 by 9%; and (3) isoproterenol increased HR, dP/dtmax and MVO2 by 53, 76 and 9%, respectively. However, all three vasodilators reduced PSCr-EDTA and PSB12 in parallel by 7-25% leaving PSCR EDTA/PSB12 unchanged. Thus, maximal estimated diffusion capacities were obtained during spontaneous coronary vascular tone, most likely reflecting maximal capillary recruitment in the Krebs-Henseleit-albumin perfused heart. The derecruiting effects of the vasoconstrictors were partly overridden by metabolic factors, while the reductions of PS after vasodilation more likely were due to increased heterogeneity in coronary flow. PMID- 8452043 TI - Local forearm and whole-body respiratory quotient in humans after an oral glucose load: methodological problems. AB - The effects of an oral glucose load of 75 g on the local forearm and whole-body energy thermogenesis were measured in normal subjects during the 4 h after the glucose intake. Simultaneous assessment of substrate metabolism in the forearm was performed. Energy expenditure (EE) increased after the glucose load and had not returned to baseline level at the end of the experiment. Whole-body respiratory quotient (RQ) was, on average, 0.80 (SD 0.05) in the baseline condition and increased to a maximum of 0.91 (0.03) and then decreased to baseline level at the end of the experiment. The local forearm oxygen uptake increased 30 min after the glucose intake and remained elevated during the rest of the experiment. The carbon dioxide output from the forearm did not increase before 90 min after the glucose load. Consequently the local forearm RQ decreased significantly from a baseline value of 0.86 (0.17) to 0.63 (0.17) 30 min after the glucose load (P < 0.05). Ninety min after the glucose load RQ increased to a maximum level at 0.95 (0.22) and decreased then gradually to baseline level. The experiments emphasize several methodological problems in the measurement of local forearm RQ. The whole-body RQ and local forearm RQ are not significantly different in the fasting state. The finding of a decrease in local forearm RQ below 0.70 30 min after the glucose load probably indicates a non-steady state in the carbon dioxide exchange. Thus, indirect calorimetry cannot be applied locally during short time periods. PMID- 8452044 TI - Regulation of glycogen synthase in human muscle during isometric contraction and recovery. AB - Six subjects performed isometric contraction (66% maximal force) to fatigue with the knee extensor muscles. Biopsies were taken from the quadriceps femoris muscle at rest, at fatigue and 1 min after termination of contraction. In three of the subjects recovery from contraction occurred in the presence of an intact circulation (non-occluded, NON) to the thigh, whereas in the other three the circulation during recovery was occluded (OCC). Glycogen synthase fractional activity (GSF) decreased in all subjects from (mean +/- SE) 0.53 +/- 0.06 at rest to 0.37 +/- 0.04 at fatigue (P < 0.001). In the OCC group GSF returned to the pre exercise value within 1 min after termination of contraction (0.59 +/- 0.07 at rest vs. 0.57 +/- 0.04 at 1 min post-exercise), whereas in the NON group GSF increased to a higher extent (0.48 +/- 0.09 at rest vs. 0.70 +/- 0.06 at 1 min post-exercise). The increase in GSF during the 1-min recovery was almost three fold higher in the NON group (0.15 +/- 0.02 vs. 0.38 +/- 0.03). Cyclic AMP dependent protein kinase (cAMP-PK) (assayed at 0/100 microM and 0.2/100 microM cAMP) did not change at fatigue or during recovery in either group. Glycogen synthase phosphatase (GSP) increased at fatigue by approximately 30% (P < 0.05 vs. rest). It is concluded that isometric contraction mediated inactivation of GS (i.e. phosphorylation of GS) is due to activation of a protein kinase(s) but not cAMP-PK. The rapid activation of GS in the NON group demonstrates that a humoral factor(s), possibly insulin and/or oxygen, is responsible for this phenomenon. PMID- 8452045 TI - The effect of iron deficiency on skeletal muscle metabolism of the rat. AB - Using 31P magnetic resonance spectroscopy we compared skeletal muscle bioenergetics in Wistar rats made chronically anaemic by being fed a diet deficient in iron for 6 weeks with chronically iron deficient animals given a normal diet as well as 5 mg iron dextran at 2 or 7 days before experimentation. Spectra of the gastrocnemius muscle were taken at rest and during stimulation of the sciatic nerve at 2 Hz for 10 min. Relative concentrations of intracellular phosphate (Pi), phosphocreatine (PCr) and ATP were determined. Iron deficiency increased PCr breakdown and production of acid in stimulated skeletal muscle. Recovery of PCr and Pi concentrations after exercise was slow. These metabolic changes are consistent with either a reduction in supply of oxygen to the muscle cell or altered oxidative phosphorylation by the mitochondria. The latter may be mediated by defective function of iron-containing proteins crucial in oxidative phosphorylation and this is suggested both by the observation that treatment with iron, sufficient to correct the anaemia, does not completely reverse the metabolic changes and that there is a different time course for such metabolic improvements and the observed increase in haemoglobin concentration. PMID- 8452046 TI - Non-invasive techniques for assessing carbohydrate flux: I. Measurement of depletion by indirect calorimetry. AB - Glycogen forms the smallest yet most labile energy substrate store. Therefore studying carbohydrate flux may be crucial to understanding the regulation of energy balance. Indirect calorimetry has been used to measure carbohydrate oxidation overnight and during exercise in nine fasted subjects. Overnight carbohydrate oxidation (averaging 2.85 +/- 0.8 g h-1) was assumed to be derived primarily from hepatic glycogen since subjects were inactive or asleep, and since glucose oxidized after gluconeogenesis from protein is measured as protein oxidation. Lower-limb muscle glycogen stores were depleted by repeated 30-min periods of cycle ergometry at 45% VO2max until exhaustion (8 +/- 1 periods). The carbohydrate oxidation rate decreased as exercise progressed. Quadratic curves yielded a close fit to each individual's exercise carbohydrate depletion data (mean multiple correlation r = 0.9996) and provided excellent inter-subject discrimination. Total (muscle plus liver) glycogen stores prior to exercise were estimated by extrapolation of the depletion curves to zero oxidation rate. This produced an extrapolation of the depletion curves to zero oxidation rate. This produced an estimate (174 +/- 61 g) which compared well with predictions (208 +/- 43 g) based on reference values for muscle mass and initial glycogen content. The results demonstrate that non-invasive estimates of glycogen status can be obtained from accurate respiratory exchange data. PMID- 8452048 TI - Genetic epidemiology. On the occasion of Professor Fini Schulsinger's 70th birthday. PMID- 8452049 TI - Fini Schulsinger's contribution to psychiatric research in genetic epidemiology. AB - During the last 3 decades, intensive cooperation between researchers in Denmark and the United States has provided important new insights into the genetic and environmental causes of mental disorders. This co-operative work has been centred around the Psykologisk Institut at Kommunehospitalet, Copenhagen, founded and directed by Fini Schulsinger, who has been the mediator of the very different kinds of research projects and who himself has also made important contributions to the understanding of nature-nurture problems within psychiatry. PMID- 8452047 TI - Non-invasive techniques for assessing carbohydrate flux: II. Measurement of deposition using 13C-glucose. AB - A non-invasive method for studying the dynamics of post-exercise carbohydrate storage by means of whole-body calorimetry and 13CO2 breath tests is described. Seven untrained glycogen-depleted subjects were offered naturally 13C-labelled high carbohydrate meals (97% by energy) at 30 min intervals for 5 h and asked to consume as much as possible. Mean intake averaged 757 +/- 211 (SD) g. Exogenous carbohydrate oxidation over 16 h calculated from gas exchange and isotope ratio measurements averaged 161 +/- 45 g, and endogenous carbohydrate oxidation averaged 31 +/- 25 g. Net carbohydrate storage, calculated as the difference between amount ingested and oxidized, was 563 g which was more than twice the measured hepatic and muscle carbohydrate oxidized during the depletion phase. After correction for body size the major determinant of glycogen storage was the amount of carbohydrate consumed (r = 0.97, P < 0.001) which in turn was determined by each subject's dietary tolerance. Post-repletion exercises (12 h after last meal) were used to remobilize freshly stored glycogen. 13CO2 enrichments indicated that a substantial part of the new glycogen was derived from the exogenous carbohydrate provided by the repletion meals. PMID- 8452050 TI - The involvement of the World Psychiatric Association in the issue of the political abuse of psychiatry. AB - This article provides a historical account of the abuse of psychiatry for political purposes and the involvement of the World Psychiatric Association (WPA) in this issue. The article focuses, particularly, on the developments from 1983 to 1989, which in many ways was crucial and determined the future of the WPA. The authors (the first, the President and the second, the Treasurer of the WPA during this period) pay tribute to Dr. Fini Schulsinger, who served as Secretary General. Through his eminent administrative capabilities, his profound understanding of ethical problems and his devotion to the basic principles of the WPA, he has substantially contributed to successfully overcoming a deep crisis with considerable impact on the identity and the moral foundations of the psychiatric profession. PMID- 8452051 TI - Genetic perspectives on crime. AB - This article examines the empirical evidence for a genetic influence in the etiology of antisocial behavior. This review relates the results of studies from 3 approaches to genetic investigation. The first, family studies, provides valuable information about the increased risk for deviance among the family members of affected individuals. Family studies provide few conclusions about genetic etiology, however, because members of families share environments as well as genes. A second approach, the study of twins, offers a somewhat better separation of genetic and environmental effects. The twin studies compare monozygotic (MZ) twins, who are genetically identical, to fraternal, same-sex, dizygotic (DZ) twins who have no more genes in common than other siblings (50%). The research design assumes that the effect of hereditary factors is demonstrated if the MZ twins have more similar outcomes (concordance for deviance) than DZ twins. The twins are reared together in almost all studies, and the environmental influences for MZ pairs may be more similar than for DZ pairs. A third approach, the adoption study, largely overcomes the possibility of confounding genetic and environmental factors which limit inferences from the results of twin studies. In this method, the deviant outcomes of adopted children (separated early in life from their biological parents) are compared with the outcomes of their adoptive parents and their biological parents. Similarity in outcome between adoptees and biological parents indicates a genetic effect. PMID- 8452052 TI - The Danish psychiatric register as a tool in epidemiology. AB - The electronic part of the nationwide Danish Psychiatric Central Register is now almost 25 years old. In this period it has proved its high value in administration, planning, treatment of patients, and not least in psychiatric research. Due to its national coverage, the register makes it easy to conduct epidemiological studies, such as analysis of trends, register linkage research, identification of representative cohorts for further analysis and follow-up studies of clinically identified cohorts. After many years of political turmoil, the register now seems to have assumed a more reasonable form, making allowance for both research interest and data protection. A proposed directive on the protection of medical data from the European Community may be a serious threat to the register and will probably eliminate all epidemiological and clinical research based on registers. PMID- 8452053 TI - The schizophrenia high-risk project in Copenhagen: three decades of progress. AB - We describe the design, theoretical approach and major recent findings of a prospective longitudinal study of the offspring of schizophrenic mothers and controls, initiated in 1962 by Sarnoff Mednick and Fini Schulsinger in Copenhagen, Denmark. Over 90% of the original 207 high-risk and 104 low-risk subjects have been successfully followed up since the initial assessment. At the time of the most recent assessment (1989), the subjects averaged 42 years of age and were nearly completely through the risk period for developing schizophrenia. By relating the lifetime psychiatric diagnoses of the subjects back to information on their premorbid experiences and functioning, we have identified several precursors of schizophrenia. This paper reviews our recent findings concerning whether outcomes of schizophrenia that differ in the relative prominence of negative versus positive symptoms represent discrete longitudinal syndromes. Predominantly negative and predominantly positive symptom schizophrenia were found to follow different patterns of symptom development from adolescence through the adult course of illness and were predicted by different combinations of genetic and environmental influences. Taken together, the findings suggest that the pathological processes underlying these two forms of schizophrenia are 1) partly independent of each other, 2) at least partly active during the premorbid state and 3) to some degree stable in the adult course of illness. PMID- 8452054 TI - A 30-year follow-up study of the sons of alcoholic men. AB - The nature-nurture question in the etiology of alcoholism is discussed. The research results from twin and adoption studies indicate a considerable genetic (= biological) component in the etiology of alcoholism. A longitudinal high-risk study of alcoholism is presented. The sons of alcoholic men and matched controls have been followed prospectively since before birth. The main results from previous phases of the study and a recent 30-year follow-up assessment are presented. PMID- 8452055 TI - The Prenatal Development Project. AB - The primary aim of the Prenatal Development Project (PDP) is to evaluate the developmental effects of prenatal exposure to steroid hormones and psychoactive drugs, particularly synthetic progestin, corticosteroids and barbiturates. Data collection has taken place at the Psykologisk Institut, now the Institute of Preventive Medicine, since 1981. The PDP database is unique for its breadth and depth as well as its combination of prospective longitudinal and cross-sectional perspectives. This article describes the database, including subject selection, perinatal information, the comprehensive contemporary evaluation and archival information from Danish registers. The unique matching procedures designed specifically for these projects and data analytic strategies are explained. The value of the PDP database is discussed both in relation to specific project aims (evaluating effects of prenatal drug exposure) and in relation to developmental and psychological research in general. PMID- 8452056 TI - Delivery of preterm and small for gestational age infants across generations. AB - Two generations of women were studied to clarify the influence of a woman's own preterm delivery or intrauterine growth retardation on her later risk of delivering preterm or growth-retarded infants. The first generation consists of the cohort of women who gave birth at the National University Hospital (Rigshospitalet) in Copenhagen from 1959 to 1961 and the second, those of their daughters that have delivered themselves. The background of the study and the procedures involved are described. The percentage of data obtained and the preliminary findings concerning the relationship between social and demographic factors and the willingness of subjects to participate are included. PMID- 8452057 TI - Does obesity run in families because of genes? An adoption study using silhouettes as a measure of obesity. AB - A number of studies, including the Danish adoption study, have shown that, in adults, the familial resemblance of obesity, as measured by the body mass index (weight in kg/(height in m)2), is mainly due to genes. The body mass index may reflect both fat and fat-free body mass. In this further analysis of the Danish adoption study, the degree of obesity was assessed by a silhouette score. There was a significant relationship in scores between the adult adoptees and their biological mothers and between the adoptees and their biological full siblings reared by the biological parents. Weaker, nonsignificant associations were found for the biological fathers and for the maternal and paternal half-siblings. There were no relationships in silhouette scoring between adoptees and adoptive parents. The results confirm the results of our previous analysis of body mass index. We conclude that human obesity is under genetic control, whereas the childhood family environment has little, if any, influence on obesity in adults. It is an important task for future research to identify the genes involved. PMID- 8452058 TI - Genes and environment in the inheritance of morbidity and mortality. AB - During the past 30 years, the Danish Adoption Registry has been used in the analysis of the effect of genes and family environment on the development of mental disorders. During the last 15 years, the registry has also been used for similar analyses of somatic disorders, including obesity and premature death from somatic disorders. This article discusses the potential problems generally related to inference on morbidity from mortality data and particularly when using mortality data in adoption studies. We conclude that further insight into the question of nature, nurture or both requires extending the studies to include morbidity data as well as mortality data. We suggest that expanding the study by including biological and adoptive siblings and by using recently developed statistical methods will considerably strengthen the adoption study of morbidity and mortality. PMID- 8452059 TI - Genes and environment in mental illness. Perspectives and ideas for future research. AB - Methodological questions in heredity-environment studies are discussed with special emphasis on schizophrenia and severe affective disorder. Mental disorder is a matter of behavioral and experimental manifestations, caused by complex interactions of genes and environment operating over a lifespan. It is therefore necessary to combine different research strategies in order to advance this field. However, progress in research is hampered by problems in classification and definition of phenotype. Accordingly, family, adoption and twin studies have a lot to contribute before molecular genetic research might be carried out. PMID- 8452060 TI - Research experiences with Fini Schulsinger. AB - For the past 31 years (1961-1992) Fini Schulsinger and I have been exploring the origins of schizophrenia. We have started a number of longitudinal projects that are still keeping us rather busy; after all, retirement just means more time for research. Through our students and these projects, our collaboration may never end. PMID- 8452061 TI - Papanicolaou smear adequacy: the effect of the sampling sequence. AB - BACKGROUND: The purpose of this study was to determine the effect of ectocervical sampling methods and sequence on Papanicolaou smear adequacy. METHODS: A randomized clinical trial was performed using either a curved cytologic sampling brush or Ayre spatula for ectocervical sampling before or after a straight sampling brush for endocervical sampling. RESULTS: The adequacy of ectocervical smears, as measured by the presence of columnar cells or squamous metaplasia, differed significantly among the four techniques studied. When the Ayre spatula was used second, 115 (69 percent) of 167 ectocervical smears were adequate compared with 75 (48 percent) of 156 smears when it was used first. Likewise, when the curved brush was used second, 116 (67 percent) of 172 ectocervical smears were adequate compared with 80 (50 percent) of 160 smears when it was used first. One hundred ninety-six (59 percent) of 332 ectocervical smears obtained with a curved brush were adequate compared with 190 (59 percent) of 323 ectocervical smears obtained with a spatula. CONCLUSIONS: The differences among the four ectocervical sampling techniques studied were due to the sequence of ectocervical sampling rather than the instrument utilized. We recommend that an ectocervical sample be obtained only after a straight brush is used to obtain an endocervical sample. PMID- 8452062 TI - Clinical trial examining effectiveness of three cough syrups. AB - BACKGROUND: Cough is one of the most common symptoms of respiratory infections for which patients seek relief. This study was done to assess the effectiveness of three commonly prescribed cough syrups. METHODS: In this multipractice, office based, randomized clinical trial, guaifenesin was compared with guaifenesin plus codeine or guaifenesin plus dextromethorphan in patients with uncomplicated respiratory tract infections. Family physicians enrolled 97 patients between February 1988 and April 1990. Patients were randomly assigned to treatment and were interviewed by telephone at 2, 4, and 10 days to assess cough relief, treatment adherence, and side effects. There were no statistically significant differences among treatment groups at base line. RESULTS: At day 2 there were no statistically significant differences among treatment groups for any of the outcome measures. At day 4 five of the outcome measures of cough quality, frequency, sleep disturbances, and absenteeism were not statistically significantly different among groups. The only statistically significant difference was the ability to keep up with usual activities, which improved least in patients assigned to dextromethorphan than in patients in other groups. There were no statistically significant differences among the three groups at day 10 for any of the outcomes. CONCLUSION: It appears that codeine, dextromethorphan, and guaifenesin are equally effective in relieving cough symptoms. PMID- 8452063 TI - The pregnancy-related dreams of pregnant women. AB - BACKGROUND: This study examined the frequency and nature of pregnancy-related dreams in pregnant women in a family practice center and assessed the extent such dreams were discussed with providers of prenatal care. METHODS: Pregnant women 18 years of age or older who were receiving prenatal care at the University of Missouri-Columbia Family Medical Care Center responded to a two-page self administered questionnaire. The major variables measured were frequency of pregnancy-related dreams, frequency of frightening dreams, content of dreams, and discussion of dreams. Health professionals providing prenatal care to these women were also surveyed. RESULTS: Eighty-eight pregnant women, 41 family physicians, and 3 nurse practitioners participated in the study. Dreams about their pregnancy or baby were reported by 59 (67 percent) of 88 pregnant women, of whom 22 had experienced at least one frightening dream. Seventeen women reported being upset by a dream. The frequency of dreams increased with advancing gestational age. The content of the most common dream involved conflict with the father of the baby. Most women had talked to another person about their dreams, usually the baby's father. Only 2 women told their physicians about the pregnancy-related dream. One half of the providers of prenatal care reported discussing pregnancy-related dreams with a pregnant patient at least once during their careers. CONCLUSION: Dreams about their pregnancy or baby occurred frequently in pregnant women and could be a neglected source of information about the psychological state of the patient. PMID- 8452064 TI - Do oral contraceptive agents affect the risk of breast cancer? A meta-analysis of the case-control reports. AB - BACKGROUND: We designed a study to assess the association of oral contraceptive use and the development of breast cancer for women in the following groups: (1) ever oral contraceptive users, (2) long-term oral contraceptive users, and (3) oral contraceptive users before a first full-term pregnancy. METHODS: A MEDLINE search of studies published in English from 1966 to 1990 was conducted using the following key words: "oral contraceptive and breast carcinoma." Eligible studies included all published case-control reports of nonduplicated data on a population (hospital or community-based). The following data were extracted from each report: country, age of subjects, number of cases and controls, whether it was a hospital or community-based study, and results. Two evaluators using a quality assessment instrument independently and blindly reviewed the methods and data analysis section from each eligible study. In the category of "ever oral contraceptive users," an estimate of the pooled relative risk with 95 percent confidence intervals (CIs) was calculated. In the categories of "duration of oral contraceptive use" and "duration of oral contraceptive use before a first full term pregnancy," Spearman's rank correlation coefficient (rs) was calculated. RESULTS: For the categories of "ever oral contraceptive users" and "long-term oral contraceptive users," no association between the use of oral contraceptives and the development of breast cancer could be detected (pooled relative risk "ever oral contraceptive users" = 1.07, 95 percent CI 0.78 to 1.36, rs "duration of use" -0.153, P = 0.189). For the category of "oral contraceptive use before a first full-term pregnancy," a significant correlation was found (rs = +0.497, P = 0.011). Many reports failed to demonstrate adequate protection against the biases most relevant to case-control methods (namely, recall bias, interviewer bias, surveillance bias, and nonresponse bias) and therefore received low-quality scores. CONCLUSIONS: This meta-analysis suggests a possible increased risk for breast cancer in women who use oral contraceptives before a first full-term pregnancy. The data, however, are confounded by studies that are generally of low quality. Further studies addressing the risk for breast cancer in oral contraceptive users need to be designed with methods that limit the biases inherent in case-control studies. PMID- 8452065 TI - Communicating about resuscitation: problems and prospects. AB - BACKGROUND: The Patient Self-Determination Act of 1991 implicitly encourages physicians to discuss advance directives and no-code orders with their patients. The medical literature to date, however, has done little to place resuscitative decision making in the context of how physicians, patients, and families communicate with one another. This paper investigates how interactions between involved parties affect the process and outcome of this decision making. METHODS: Participant observation and open-ended interviews were conducted with patients, their families, resident physicians, and family medicine faculty members. RESULTS: This report describes three social and cultural issues that commonly influence and shape the process of do-not-resuscitate decision making: judging competency and capacity, dealing with uncertainty, and recognizing attitudes toward death. CONCLUSIONS: Improved understanding of the communicative process can facilitate the establishment of meaningful, therapeutic alliances between physicians, patients, and families at an influential juncture in the family life cycle. PMID- 8452066 TI - A description of the content of army family practice. AB - BACKGROUND: For decisions about residency curricula and downsizing the US Army medical corps, decision makers must know the practice content of the various specialties. Little is known about the content of Army family practice. The purpose of our study was to describe the content of Army family practice. METHODS: We analyzed a random sample of 28,849 family practice encounters from the US Army Ambulatory Care Data Base Study. Variables included patient demographics, diagnoses, visit duration, procedures, and medical facility. Patient age and visit duration were compared using analysis of variance; facility profiles were compared by age category and sex of patients, family member position, and procedure frequency using chi-square analysis. Diagnostic content of the facilities was compared by both chi-square and Kendall's tau B tests. RESULTS: The typical patient was a 26-year-old woman. The 25 most frequent diagnoses accounted for three-fourths of all encounters, with variation by patient age. The majority of visits did not include a procedure, but procedure frequency varied by patient age and diagnostic certainty. Mean visit duration was 16.4 minutes and varied by age. There were differences among the sites for all variables. CONCLUSIONS: Army family physicians see patients of all ages, of whom more are the family members of soldiers than the soldiers themselves; they frequently do procedures and are usually certain of their diagnoses, which include a broad spectrum of illnesses. Army family physicians are flexible, adapt to local patient and environmental needs, and are uniquely qualified to form the basis of Army medicine. PMID- 8452067 TI - Guidelines for postmenopausal preventive hormone therapy: a policy review. American College of Physicians. PMID- 8452068 TI - The physician's role in health care reform. AB - Health care in the United States is in crisis. The desire to provide care continually conflicts with the need to contain costs. Historically, physicians have opposed the demand for health care reform, and although many physicians have responded to the current crisis with ambivalence, apathy, or frustration, they have the knowledge, capability, and opportunity to advocate for and to effect reform within the health care delivery system. Many believe that the acknowledgment of costs as a factor in treatment decisions compromises their role as patient advocates, but in the face of increasing government controls and the corporatism of medicine, the human link between physician and patient is even more valuable. The current crisis in health care necessitates cost control. If physicians conscientiously undertake their political, professional, and personal roles, they can reform the health care delivery system in the United States while compassionately advocating for their patients. PMID- 8452069 TI - Bilateral primary renal lymphoma. PMID- 8452070 TI - Fracture care by family physicians. AB - This report helps characterize fracture management by family physicians. The findings suggest that family physicians can care for a broad range of acute fractures with healing times at least comparable with the standard of care described by orthopedists. A prospective trial would be necessary to assess fully clinical outcomes resulting from specific fracture management. That distal extremity fractures predominated should guide educators in their decision regarding orthopedic training. PMID- 8452071 TI - Patients on patienthood: new voices from the high-tech area. PMID- 8452072 TI - Cardiopulmonary resuscitation as a medical intervention. PMID- 8452073 TI - Premature labor. PMID- 8452074 TI - Roles of family physicians. PMID- 8452075 TI - Limits of technology. PMID- 8452076 TI - Streptococcal toxic shock. PMID- 8452077 TI - In-hospital cardiopulmonary resuscitation: a 30-year review. AB - BACKGROUND: We performed a meta-analysis to: (1) assess the disputed issue of in hospital cardiopulmonary resuscitation (CPR) success rates among elderly patients, (2) investigate the possibility of a declining CPR success rate between 1960 and 1990, (3) provide an overview estimate of CPR effectiveness in specific patient groups, and (4) assess CPR risks. METHODS: Ninety-eight reports providing in-hospital CPR survival-to-discharge rates were included in this overview. These reports were identified from MEDLINE searches, previous reviews, and reference citations. RESULTS: A pooled analysis revealed that 2994 (15 percent) of 19,955 patients were successfully resuscitated (survival to discharge). The rate of successful CPR has not changed in 30 years (r = -0.14, P > 0.05), but there has been a steady decline in the optimism regarding its value (r = -0.29, P < 0.01). Patients younger than 70 years of age had a success rate of 16.2 percent (odds ratio = 1.36; 95 percent confidence interval, 1.20 to 1.53) versus 12.4 percent for patients older than 70 years (P < 0.001). Community hospitals had a higher CPR success rate than teaching hospitals (18.5 percent versus 13.6 percent, P < 0.001). Although 72.9 percent of the post-CPR deaths were within 72 hours, prolonged in hospital survival in a vegetative state did occur; 1.6 percent of successfully resuscitated patients had a permanent neurological impairment. CONCLUSION: The increasing pessimism about the value of CPR, specifically, its futility in the elderly patient, is not supported by this review. The results of this meta-analysis should assist both the physician and the patient in determining the probable outcome of CPR. PMID- 8452078 TI - [Italian-style surgical resection practiced by surgeon Martin de Castellanos at the Escorial in 1594]. AB - The science of urology emerged as a specialty in Spain three centuries earlier than in the rest of Europe. Publication of the Treaty of Urology by Francisco Diaz in 1588 and the founding of a permanent professorship in Madrid in 1612 for the teaching and treatment of urological conditions, represent the most relevant background for the future and still distant development of the specialty. In this paper we disclose new biographical data on the scholar Martin de Castellanos, first professor 'of Urology' in the history of Medicine and briefly discuss the innovation that the founding of the chair meant for the future regulations of this surgical specialty. PMID- 8452079 TI - [Endourologic treatment of tumors of the superior urothelium: results and clinical course]. AB - Presentation of 31 patients with suspected diagnosis of upper urothelium tumour seen between 1986 and 1991. In agreement with our study protocol and the endourological treatment followed in this type of tumours, there were eight false positive, which were excluded. Five cases were treated by retrograde ureterorenoscopy while in the remaining 18 cases the anterograde percutaneous approach was used. A review of both the aspects of endoeurological treatment and the evolution of these patients during that period is included. PMID- 8452080 TI - [Primary adrenal carcinoma]. AB - A series of 17 patients with primary adrenal cortical carcinoma is presented. Of 14 patients without evidence of disseminated disease prior to radical surgery, 6 developed distant metastases during follow-up. The mean interval free of disease in these patients was 12 months (range 3-40) and the median survival 15 months. Of the six patients in whom adjuvant external beam radiotherapy was delivered, no evidence of local recurrence was observed. Of the patients treated without external beam radiotherapy, 3 local failures were observed. The projected 5 years survival was 35%, which is similar to that reported in the literature. To date, there is no evidence that chemotherapy nor radiotherapy could improve the survival, however, radiotherapy might increase the local control in selected cases. PMID- 8452081 TI - [Treatment of recurrent bladder surface tumors with laser Nd:Yag: a single-year experience]. AB - Management of surface vesical tumours using laser photocoagulation has proven to be a safe and effective method. The technique can be performed under anaesthetic sedation and in the outpatient clinic environment thus allowing a considerable cost saving and the reduction of hospital's waiting lists. Throughout 1990, 47 patients with relapsing vesical tumours were treated in 55 sessions. Most cases were performed on ambulatory patients with a low complications rate and an estimated saving of 18,326,400 pesetas as compared to transurethral resection. PMID- 8452082 TI - [Testicular germinal cell tumors. Authors' case load. Treatment review]. AB - This article reports our case series of testicle germinal cell tumours, consisting of 14 cases, between 1974-1991. 42.85% (6 cases) were seminomas, 4 (66.6%) in Stage I. There was one case (16.6%) in Stage III and another one in Stage IV. 14.29% (2 cases) were embryonic carcinomas, one in Stage I and one in Stage II. Teratomas represented 14.29% (2 cases), in Stages I and IV respectively. There were 4 cases of mixed tumours (2 cases) in which teratomatous components (3 out of 4) were predominant. 50% were in Stage I and 50% in Stage III. Inguinal orchiectomy was performed in all cases, and three received radiotherapy (seminomas in Stages I (2 cases) and III), with survival ranging from 1 to 7 years. Two cases (seminoma and embryonic carcinoma) received chemotherapy under different regimes depending on the time of diagnosis. One patient has survived 11 years following rescue lymphadenectomy while the other one died 14 months later from pulmonary metastasis. Among the mixed tumours, 50% (2 cases in Stages II and III) died 5 and 11 months afterwards without further treatment due to overall affectation at diagnosis. An abstentionist approach in Stage I (seminomas and non-seminomas), which was "strictly" applied in 5 cases showing disease-free survival ranging from 1 to 5 years, is defended. Follow-up was not feasible in 2 cases (14.2%). Both the diagnostic means and a review of treatment by Stages, reflecting the evolution of chemotherapy and the results obtained, are analyzed. Also the most widely accepted approaches in the management of these tumours. PMID- 8452083 TI - [Ambulatory treatment without anesthesia of urinary lithiasis by extracorporeal shock-wave lithotripsy: 7,000 cases]. AB - Exposition of results and complications in 7,162 consecutive sessions with Shockwave Extracorporeal Lithotripsy (SWEL) applied to 3,950 lithiasis located at all levels of the urinary tract. These procedures have been performed without sedation or anaesthesia. Diuresis was not forced during or after treatment with serotherapy, mannitol, or diuretics. Treatment was conducted in an outpatients clinic in all cases. The treatment/lithiasis ratio in this initial series was 1.7. Following therapy, 7.09% of patients treated attended the emergency unit due to colic pain/fever. 3.60% of patients treated required hospitalization due to major complications: subcapsular-retroperitoneal haematoma, 9 cases; ureteral obstruction, 120 cases; septicemia, 22 cases; renal function annulment, 11 cases and death, 2 cases. PMID- 8452084 TI - [Idiopathic granulomatous orchitis]. AB - Idiopathic granulomatous orchitis is a rare testicle lesion of unknown etiology. This paper illustrates 10 cases studying their presentation, location, ultrasound and histological diagnosis and therapy. A testicular injury background and self immune reaction appear as likely causes of this entity. Differential diagnosis with testes malignant tumours can only be reached after orchiectomy and a subsequent histological examination. PMID- 8452085 TI - [Renal hypertrophy studied by techniques of nuclear medicine in post-nephrectomy patients]. AB - Study of group of 61 patients, nephrectomized as a result of various diseases and who before and three months after surgery underwent blood pressure, effective renal plasma flow (EPFF) and unilateral renal function determinations in order to verify the compensating ability of the remaining kidney. Effective renal plasma flow was determined by a single injection and removal of six serial blood samples with 125-I-Hippuran. Unilateral renal function was determined from the relative uptake of 99mTc-DMSA 24 hours after injection. The patients were divided into four groups according to their overall and unilateral renal function as well as the presence or absence of hypertension. Patients with normal EPFF and symmetrical renal function showed a significantly increase in the function of the remaining kidney after surgery (p < 0.001). Patients with normal or slightly reduced EPFF (< 10%) and highly asymmetrical unilateral function as well as those with decreased EPFF (> 10%) and symmetrical or asymmetrical unilateral renal function did not increased the function of the remaining kidney after nephrectomy, and hypertensive patients whose blood pressure returned to normal values after nephrectomy had a decreased function of the remaining kidney after surgery (< 0.001). It is concluded that it is possible to predict the functional behaviour of the remaining kidney after nephrectomy, and that the compensating ability will basically depend on the previously existing (overall and unilateral) renal function as well as the presence or absence of hypertension. PMID- 8452086 TI - [A program of intracavernous drug-induced erection for the treatment of impotence]. AB - The study includes 138 patients with erectile dysfunction, all of them previously treated with intracavernous injections. Following study and classification of the type of impotence, they were all included in one of the four following groups. The drugs used were, in group I (73 patients) Prostaglandins E1, in group II (37 patients) Papaverine, in group III (6 patients) a combination of Papaverine and Phentolamine and in group IV (22 patients) a combination of Papaverine and Prostaglandins E1. We found a good treatment response in 59.3% cases (60.3% in group I, 51.3% in group II, 66.7% in group III, and 69% in group IV). We outline the better results obtained in group IV, as well as the reduced number of complications in our series. PMID- 8452087 TI - [Local anesthesia in the surgical management of hydrocele and cysts of the spermatic cord]. AB - Traditional management of vaginal fluid collections has always been surgery. The benignancy of this disease does not correspond with the morbidity caused by the anaesthetic techniques used. Over the last few years, sclerotherapy has become increasingly attractive as an alternative to hydrocelectomy. Indications are, nonetheless, restricted, presenting a relapse rate which varies according to the substance used and the operating team. The study proposes the use of local anaesthetics for the surgery of vaginal fluid collections so as to minimize the immediate postoperative period and thus the hospital stay. Between May and October 1991, 55 patients, 49 with hydrocele (4 bilateral) and 6 with sperm cord cyst, were treated in our Unit. Patients were monitored in the theatre (EKG, blood pressure and oximeter) to supervise their life constants, and 2% Mepivacaine (10-20 cc) was infiltrated into the sperm cord and the area of scrotal wall to be cut. Surgical techniques range from dissection to scission of the bag until partial eversion, requiring the use of reabsorbable suture and a careful haemostasis to avoid drainage. Anaesthetics tolerance has been highly satisfactory in 52 patients (94%), good in one patient (2%) and unsatisfactory in two cases (4%). Recorded complications include: severe bradycardia and hypotension in one case (2%), persistent right renoureteral pain in one case (2%), scrotal haematoma in 5 cases (9%) and suture dehiscence in another patient (2%). It is concluded that surgical management of vaginal collection with local anaesthetics is feasible, and reduces the immediate postoperative period also avoiding morbidity derived from a more aggressive anaesthetic technique. PMID- 8452088 TI - [Tumors of the female urethra: presentation of cases and review of the literature]. AB - Female urethra tumours are rare conditions and so the series presented in the literature gathers just a few cases, and therefore is difficult to reach a conclusion with regard to the definite treatment to be adopted in each case. It appears to be certain that even histologically malignant forms of this disease can be cured in the earlier stages. The most representative cases presented in our experience are analyzed and an overall review of the literature is made aiming to examine the experience of various authors with regard to the diagnosis and treatment of the injuries. PMID- 8452089 TI - [Metastasizing adenocarcinoma of the colon in a patient with ceco-cystoplasty]. AB - Augmentation and substitution erocystoplastias are currently widely accepted techniques for the treatment of several benign and malignant diseases. Appearance of neoplasia on the various gut segments used after a latency period ranging from 5 to 25 years following initial surgery has been described. The paper presents one case of metastatic colon adenocarcinoma initially located in the region of ureteral reimplantation, in a patient with augmentation cecocystoplastia performed as a result of vesical retraction secondary to genitourinary tuberculosis. Appearance of this type of neoplasia in an increasing population, quite often young, compels the urologist to keep a tight watch. Endoscopic monitoring of the new bladder is the most effective diagnostic procedure. A once a-year endoscopy after an interval as yet not definitely established, but which could be around 10 years after initial enterocystoplastia, seems advisable at least in cases at higher risk. PMID- 8452090 TI - [Acute focal bacterial nephritis in a case of AIDS]. AB - Presentation of one case of bacterial acute focal nephritis (acute lobe nephrosis) in a parenterally drug-abuser, HIV-infected male. From the clinical point of view, the picture was interpreted as acute hepatitis, and the lesion was detected by ultrasound techniques. A right side location, relative lack of urological symptoms and coexistence of a chronic liver disease contributed to the diagnostic error. Failure of initial response to therapy with antibiotics coincided with the lesion migration. Eventually, the case evolved favourable with conservative treatment. PMID- 8452091 TI - Physiological, biochemical and genetic control of bacterial bioluminescence. PMID- 8452092 TI - Fruiting in the higher fungi. PMID- 8452093 TI - Bacterial ice nucleation. PMID- 8452094 TI - Sex hormones and fungi. PMID- 8452095 TI - American Roentgen Ray Society, 93rd annual meeting. San Francisco, California, April 25-30, 1993. Abstracts. PMID- 8452096 TI - Evaluation of an earphone-support device for measuring earplug attenuation. AB - A new procedure for determining the attenuation of earplugs with a standard audiometric headset was evaluated. The procedure utilized a device that supports a conventional supraaural earphone cushion (MX-41/AR) such that it does not contact the pinna or the earplug during threshold measurement. The attenuation provided by a foam earplug was estimated on a group of normal-hearing subjects using this method. The resulting attenuation values were compared to data obtained using sound field (ANSI S12.6-1984) methods, and to values obtained by simply placing the earphone on the pinna. Results suggest that the test re-test reliabilities of both the earphone-support method and the earphone-only method were comparable to that of the sound field procedure. Also, of the four test frequencies employed (1, 2, 3 and 4 kHz), the closet correspondence between attenuation estimates obtained using the ANSI procedures and estimates obtained with the support device occurred at 1 and 2 kHz. PMID- 8452097 TI - Loading and filtration characteristics of filtering facepieces. AB - Most filtering facepieces used today are made of electret material (material with significant electrical charges on the filter fibers). Because of the addition of this electrical removal force, the filtration efficiency can be significantly increased without increasing the air pressure drop inside the respirator; pressure drop is closely related to physiological load. However, the removal by electrical forces is reduced in time, as aerosols deposit on the filter fibers. We have studied the contribution of this electrical removal and its change in time as a function of aerosol loading. To prove the change in aerosol penetration is due to the reduction of electrical force, the electrical charges were removed from new facepieces by the application of appropriate chemicals. The dust-mist filtering facepieces tested have similar fiber diameters and packing densities, as determined by scanning electron microscopy and pressure drop data. At a face velocity of 10 cm/s (corresponding to 100 L/min through a complete filtering facepiece) and an aerosol size of 0.16 microns, electrical force removal accounts for 69% of the total filtration for the respirator found to have the best filter quality but only 25% for the respirator (from a different manufacturer) found to have the worst filter quality. Our experimental data show that the removal efficiency of these facepieces is reduced in time by as much as this amount. However, under normal wear conditions, the total aerosol particle load is not as high as shown and the filtering facepieces are likely to be discarded before the fiber charges (i.e., the electrostatic attractions) are significantly diminished. PMID- 8452098 TI - Assessment of arsenic exposures and controls in gallium arsenide production. AB - The electronics industry is expanding the use of gallium arsenide in the production of optoelectronic devices and integrated circuits. Workers in the electronics industry using gallium arsenide are exposed to hazardous substances such as arsenic, arsine, and various acids. Arsenic requires stringent controls to minimize exposures (the current OSHA PEL for arsenic is 10 micrograms/m3 and the NIOSH REL is 2 micrograms/m3 ceiling). Inorganic arsenic is strongly implicated in respiratory tract and skin cancer. For these reasons, NIOSH researchers conducted a study of control systems for facilities using gallium arsenide. Seven walk-through surveys were performed to identify locations for detailed study which appeared to have effective controls; three facilities were chosen for in-depth evaluation. The controls were evaluated by industrial hygiene sampling. Including personal breathing zone and area air sampling for arsenic and arsine; wipe samples for arsenic also were collected. Work practices and the use of personal protective equipment were documented. This paper reports on the controls and the arsenic exposure results from the evaluation of the following gallium arsenide processes: Liquid Encapsulated Czochralski (LEC) and Horizontal Bridgeman (HB) crystal growing, LEC cleaning operations, ingot grinding/wafer sawing, and epitaxy. Results at one plant showed that in all processes except epitaxy, average arsenic exposures were at or above the OSHA action level of 5 micrograms/m3. While cleaning the LEC crystal pullers, the average potential arsenic exposure of the cleaning operators was 100 times the OSHA PEL. At the other two plants, personal exposures for arsenic were well controlled in LEC, LEC cleaning, grinding/sawing, and epitaxy operations. PMID- 8452099 TI - Leptomeningeal toxoplasmosis after allogeneic marrow transplantation. Case report and review of the literature. AB - A 37-year-old woman with chronic myelogenous leukemia underwent allogeneic bone marrow transplantation with CD8-depleted marrow from an HLA-identical sister. On day 43 post-transplant, the patient developed a headache and became lethargic and tremulous. Magnetic resonance imaging (MRI) of the brain showed abnormal meningeal and superficial parenchymal enhancement anteriorly. The spinal fluid had an elevated protein level with normal glucose and a neutrophilic pleocytosis. At autopsy, Toxoplasma meningoencephalitis was seen. On review of the literature, headache and confusion at 1-2 months post-transplant are common presenting signs of central nervous system toxoplasmosis. The predominance of neutrophils in the spinal fluid in this patient probably reflects the meningeal component of the infection and is an unusual finding. The presentation of toxoplasmosis in marrow transplant recipients is quite pleomorphic, and a definite diagnosis is difficult to obtain antemortem. Empiric therapy with pyrimethamine and sulfadiazine should be considered for marrow transplant recipients with neurologic deficits for which there is no other apparent etiology. PMID- 8452100 TI - Detection of early anthracycline cardiotoxicity by monitoring the peak filling rate. AB - Three patients developed clinical congestive heart failure after cumulative doxorubicin doses of 264, 440, and 450 mg/m2, respectively, despite serial monitoring of systolic cardiac function by resting gated radionuclide scanning. All three patients had depressed diastolic function, as shown by a decreased peak filling rate preceding a change in systolic function, which was assessed by left ventricular ejection fraction prior to the development of clinical congestive heart failure. We recommend serial monitoring of the peak filling rate, in addition to left ventricular ejection fraction. If broader experience confirms our impression that the peak filling rate is more sensitive than the current standard assessment of left ventricular ejection fraction, new guidelines may need to be drawn to monitor cardiotoxicity of anthracyclines and anthraquinones. PMID- 8452101 TI - Doxorubicin plus metronidazole in the treatment of recurrent or metastatic squamous cell carcinoma of the head and neck. AB - Twenty-five patients were treated on a Phase II study of doxorubicin, 60-75 mg/m2 intravenously every 3 weeks, accompanied by metronidazole, 1500 mg/m2 orally 12 hours and immediately before the doxorubicin and 6 hours and 24 hours after the doxorubicin. Of 23 patients evaluable for response, 2 (9%) achieved complete remissions, 2 (9%) achieved partial remissions, and 4 (18%) were stable (one of whom achieved a minor response). One patient with an inoperable biopsy-proven 4 x 3 x 3 cm recurrence following radiation and surgery has had a complete remission that persists at 8 years. The second patient who achieved a complete remission subsequently underwent surgical resection of the involved area. No residual tumor was found, and he remains disease free after 8.5 years. Doxorubicin toxicity did not appear to be augmented significantly by metronidazole. Although the response rate seen in this study was low, the occurrence of two long-term complete remissions suggests that this combination should be studied further in other tumor types. PMID- 8452102 TI - Antiestrogenic potency of toremifene and tamoxifen in postmenopausal women. AB - In this nonblinded, controlled multicenter trial, postmenopausal women were randomly assigned to receive graded doses of toremifene and tamoxifen or no antiestrogen to assess dose-response levels and evaluation methodology. For standardization, transdermal estradiol (Estraderm-Ciba Geigy) was applied to all women for 38 days. The antiestrogens were added on days 29-38. For control and all treatment groups, there were no significant changes in serum chemistries or serum hormone levels, nor were there differences in adverse effects. The use of continuous estradiol precluded any meaningful assessment of the estrogenicity of tamoxifen or toremifene. As measured by vaginal superficial cytologic cell count changes, the antiestrogenic activity of toremifene doses ranging from 20 to 200 mg/day could not be distinguished from that of 20 mg/day of tamoxifen, the clinically recommended dose in North America. PMID- 8452103 TI - Cisplatin, cytosine arabinoside, and pentoxifylline in the treatment of squamous cell carcinoma of the head and neck. AB - Nine patients were entered on a Phase I-II study of cisplatin, cytosine arabinoside, and pentoxifylline in the treatment of advanced head and neck cancer. The treatment regimen consisted of cisplatin 100 mg/m2 intravenously on day 1 only, cytosine arabinoside 2,000 mg/m2 intravenously on days 1 and 2, and pentoxifylline 400 mg orally three times daily beginning 7 to 14 days before the chemotherapy. The pentoxifylline was continued between chemotherapy cycles. Chemotherapy courses were repeated at 3- to 4-week intervals. Partial remission were seen in two patients, two patients were stable, and five patients failed on treatment. Dose-limiting toxicity was granulocytopenia. Pentoxifylline itself caused some nausea and anorexia. Although the patient numbers were small, there was no indication that pentoxifylline increased the efficacy of this chemotherapy in head and neck cancer. It is possible that another dose schedule might have been more effective. PMID- 8452104 TI - The myeloprotective effect of recombinant human granulocyte-macrophage colony stimulating factor given sequentially with continuous infusion vinblastine in metastatic breast cancer patients. AB - Colony-stimulating factors have been shown to have a myeloprotective effect when administered following chemotherapy. Chemotherapy of short duration with predominantly cell-cycle nonspecific agents has been most used. The myeloprotective effects of colony-stimulating factors given after cell-cycle specific or continuous infusion chemotherapy have not previously been assessed. Twenty-one evaluable patients with metastatic breast cancer progressing after one prior chemotherapy regimen were treated with continuous infusion vinblastine 2.0 mg/m2/day for 5 days. After the second chemotherapy cycle, granulocyte-macrophage colony-stimulating factor (GM-CSF) was given for 10 days. Serial complete blood counts, differential, and platelet counts were obtained to document myelotoxicity. GM-CSF administration resulted in a significantly shorter duration of granulocytopenia, < 500/microliters, at the maximum GM-CSF dose. Significantly more rapid recovery of granulocytes to > 500/microliters, > 1000/microliters, and > 1500/microliters was seen with all doses and schedules of GM-CSF administered. The nadir absolute granulocyte counts were unaffected. GM-CSF given after continuous infusion cell-cycle specific chemotherapy is therefore myeloprotective. PMID- 8452105 TI - Phase II trials of tetrahydropyranyl-adriamycin (Pirarubicin) on renal and colon carcinoma, melanoma, and soft tissue sarcoma. AB - Eighty patients with measurable metastatic colon or renal cancer, melanoma, or sarcoma entered these Phase II studies. A dose of 25 mg/m2/day of Pirarubicin (THP) for 3 consecutive days every 4 weeks for the first patients, and then 20 mg/m2/day for 3 days every 3 weeks was given by i.v. push. These patients received 225 cycles for a median cumulative dose of 165 mg/m2 (range: 55-630). The mean number of cycles given was 2.8 (range: 1-8). Only 3 partial responses and 18 stable disease (22%) were observed. Hematologic toxicity was the main problem; it was responsible for one death and a 19% and 44% incidence of grade 3 and 4 WHO neutropenia, respectively. Alopecia was rare (4%). Chemotherapy was discontinued in three cases because of suspicion of cardiac toxicity, but only one patient had a significant drop in left ventricular ejection fraction at a cumulative THP dosage of 120 mg/m2. A lack of efficacy in renal and colon cancer and melanoma was presupposed and confirmed by these trials. Due to pretreatment with anthracycline in most patients, definite evaluation of THP in soft tissue sarcoma could not be given. PMID- 8452106 TI - Age-race interaction in prostatic adenocarcinoma treated with external beam irradiation. AB - The most important predictors of long-term survival in patients with adenocarcinoma of the prostate are histological grade and stage of disease. However, the role of other epidemiological factors, particularly age and race, remains controversial. There is a school of thought that black patients and younger patients have a biologically more aggressive disease. We analyzed the survival of 914 patients (867 whites and 47 blacks) with localized adenocarcinoma of the prostate treated with external beam irradiation from the Connecticut SEER Tumor Registry data base. Patients were treated from 1973-1987, and those with Stages A1, A2 and D2 were excluded. Patients < or = 60 years of age had a 5-year survival rate of 72% compared to 61% for those > 60 years of age (p = 0.06). When stratified by race, white patients had a 63% 5-year survival rate versus 47% in black patients (p = 0.02). When analyzed by race and age, and age-race interaction was noted. Although younger whites fared better than older whites, 77% versus 61% survival at 5 years (p = 0.02), younger blacks fared worse than older blacks, 31% versus 52% survival at 5 years (p = 0.21). Blacks, on average, presented at an earlier age than whites, 65 years versus 69 years (p = 0.001). Both races had similar stage and similar grade of disease. In older patients, both races presented with similar stage and grade of disease and had similar survival. However, in the younger age group, black patients presented with similar grade, but higher stage disease than whites. This may explain the worse survival in young blacks compared to young whites, 31% versus 77% at 5 years (p = 0.007). Multivariate analysis revealed that, even controlling for stage and grade, blacks still fared worse than whites. Increased age was associated with decreased survival in whites but increased survival in blacks. PMID- 8452107 TI - Piritrexim-induced pulmonary toxicity. AB - We describe a patient with transitional cell carcinoma of the renal pelvis who developed respiratory dysfunction and an abnormal chest x-ray with diffuse interstitial opacities while on chemotherapy with piritrexim, a methotrexate analog. Drug discontinuation resulted in complete resolution of the clinical and radiographic picture. The pulmonary toxicity is probably induced by piritrexim. PMID- 8452108 TI - A phase II trial of medroxyprogesterone acetate in epithelial ovarian cancers. A Gynecologic Oncology Group study. AB - Twenty-four evaluable patients with advanced or recurrent epithelial ovarian carcinoma who progressed on platinum-containing combination chemotherapy were treated with medroxyprogesterone acetate (C.T. Provera) 50 mg orally three times a day until progression of disease. One patient had a partial response (4.2%), 9 patients had stable disease (37.5%), and 14 (58.3%) had increasing disease. The 95% upper confidence limit for response is less than or equal to 18.3%. There was no toxicity associated with its use. C.T. Provera has limited activity in patients with epithelial ovarian cancer who have failed combination chemotherapy. PMID- 8452109 TI - Phase II trial of carboplatin in patients with metastatic malignant melanoma. A report from the Eastern Cooperative Oncology Group. AB - Thirty patients with pathologically proven, measurable metastatic melanoma without prior chemotherapy were treated with carboplatin 400 mg/m2 by intravenous infusion for 30 minutes every 4 weeks. Twenty-seven patients were evaluable for response and toxicity. Two complete responses and one partial response (3 of 27 = 11%, 90% confidence intervals: 3-26%) were documented. The median survival was 4.7 months. The most common toxicity was myelosuppression. One drug-related death was observed due to renal failure. Prior radiotherapy and liver metastasis were the poor prognostic indicators identified in our study. Carboplatin in the dose and schedule reported in our trial has only modest antitumor activity in patients with advanced malignant melanoma. PMID- 8452110 TI - Phase II multicenter study of epirubicin for hormone-resistant prostatic cancer with measurable soft tissue disease. AB - Twenty-six patients with prostatic cancer were treated with courses of epirubicin at 3-week intervals, starting at an initial intravenous dose of 75 mg/m2. All patients had progressive disease after orchiectomy and/or antiandrogen therapy and had measurable soft tissue lesions. There were three partial responders (response rate: 12%; 95% confidence limits: 4-29%). Major toxicity was myelosuppression, and there were two drug-related deaths. Epirubicin in this dose and schedule cannot be recommended for treatment of prostatic cancer. PMID- 8452111 TI - Recombinant human gamma interferon administered by continuous intravenous infusion in acute myelogenous leukemia and myelodysplastic syndromes. AB - Nine patients (median age, 58; range: 37-74) with relapsed de novo acute myeloid leukemia (AML) (3), AML after prior myelodysplastic syndrome (MDS) (4), or MDS (2) were treated with 2-20 x 10(6) U/m2/day (1-10 mg/m2/day) of recombinant human interferon gamma (rIFN gamma; Biogen) on a 14-day continuous intravenous infusion schedule. The two patients who received the initial dose of 20 x 10(6) U/m2/day (1.0 mg/m2/day) could only tolerate 6 days of therapy because of severe hepatotoxicity. Two patients who received the revised starting dose of 10 x 10(6) U/m2/day also could not complete a full course of rIFN gamma due to renal failure in one case and pulmonary deterioration in the other. A reversible dose-related rise in SGOT was seen in six patients. All patients developed a severe flu-like syndrome characterized by myalgias and fevers. These toxicities were not associated with detectable serum levels of tumor necrosis factor (TNF). Although blasts from three of five assessable patients displayed increased expression of the Ia (HLA-DR) antigen, there were no hematological responses. Steady-state rIFN gamma plasma levels in patients who tolerated a complete infusion were < 40 U/ml, a concentration below that required to induce differentiation of myeloid leukemic cell lines in vitro. We conclude that continuous infusions of rIFN gamma at doses as low as 2 x 10(6) U/m2/day are poorly tolerated in patients with AML and MDS; the maximum tolerated dose is approximately 2 x 10(6) U/m2/day. PMID- 8452112 TI - Fast neutron radiotherapy for locally advanced prostate cancer. Final report of Radiation Therapy Oncology Group randomized clinical trial. AB - Between June 1977 and April 1983 the Radiation Therapy Oncology Group (RTOG) sponsored a Phase III randomized trial investigating the use of fast neutron radiotherapy for patients with locally advanced (Stages C and D1) adenocarcinoma of the prostate gland. Patients were randomized to receive either conventional photon radiation or fast neutron radiation used in a mixed-beam (neutron/photon) treatment schedule. A total of 91 analyzable patients were entered into the study, and the two patient groups were balanced with respect to the major prognostic variables. Actuarial curves are presented for local/regional control and "overall" survival. Ten-year results for clinically assessed local control are 70% for the mixed-beam group versus 58% for the photon group (p = 0.03) and for survival are 46% for the mixed-beam group versus 29% for the photon group (p = 0.04). This study suggests that a regional method of treatment can influence both local tumor control and survival in patients with locally advanced adenocarcinoma of the prostate gland. PMID- 8452113 TI - Schedule in Cf-252 neutron brachytherapy: complications after delayed implant therapy for cervical cancer in a phase II trial. AB - The objective of this study was to review severe complication frequency in a protocol study using a defined prescribed dose combined with fractionated whole pelvis radiotherapy to 40-45 Gy. The method used a dose of Cf neutrons to 35 Gy equivalents (relative biological effectiveness or RBE adjusted) to a total tumor dose of 80 Gy-eq in one to four implant sessions. Compliance was excellent, and most patients received two implants to 35 (0.4) (SE) Gy-eq in two sessions plus external radiation to a total point A or paracervical region dose of 80 (0.3) Gy eqs. In patients who received delayed implants, the severe complication rate (pelvic necrosis, fistulas) was significantly greater (40% versus 3%). We postulate that neutron brachytherapy caused tumors to regress rapidly and completely, which allowed the neutron dose to adjacent radiosensitive organs (bladder, rectum, sigmoid colon, and bowel) to become excessive. The delayed Cf implant apparently contributed to the greater risk for normal tissue complications. PMID- 8452114 TI - Randomized comparison of the antiemetic efficacy of a serotonin type 3 receptor antagonist (MDL 72,222) with a high-dose metoclopramide regimen. AB - This pilot randomized study compared MDL 72,222, a highly selective 5-HT3 receptor antagonist, with a high-dose metoclopramide regimen (HDM) for chemotherapy-induced nausea and vomiting. MDL 72,222 was given in 20 mg intravenous doses 30 minutes before chemotherapy, as well as 2, 6, and 12 hours after chemotherapy infusion. The HDM was composed of diphenhydramine 50 mg i.v., metoclopramide 2 mg/kg i.v., and lorazepam 0.04 mg/kg i.v. administered 30 minutes before chemotherapy and 2, 4, 6, and 8 hours after chemotherapy. Patients were randomized to either MDL 72,222 (n = 12) or the HDM (n = 12) and were matched for age, weight, Karnofsky performance status, and chemotherapy. More patients in the MDL 72,222 group had received prior cisplatin. The MDL 72,222 group and the HDM group received a mean cisplatin dose of 66 mg/m2 and 62 mg/m2, respectively. Patients were observed for retching and/or emesis for 24 hours and completed a visual analog scale (VAS) for nausea. Six MDL 72,222 and five HDM patients had no vomiting. One MDL 72,222 and two HDM patients had one episode of emesis within 24 hours of chemotherapy. The median number of emetic episodes in the first 24 hours was 0.5 for MDL 72,222 and 1.0 for HDM patients. HDM patients were frequently asleep and were not awakened for evaluation of nausea with the VAS; 58% (70 of 120) of the HDM (mean score: 19.1 mm) and 14% (17 of 119) of the MDL 72,222 (mean score: 17.1) patients could not have VAS scores obtained (X2 = 50.74, p < 0.001). MDL 72,222 had similar efficacy with less sedation, and further trials are warranted. PMID- 8452115 TI - A phase II study of 5-fluorouracil, cisplatin, and 4'-epirubicin in the treatment of advanced solid cancers. AB - This phase II study was designed to assess the therapeutic potential of intensive course treatment with three anticancer agents: 50 mg of cisplatin on day 1, 40 mg/m2 of epirubicin on day 2, and 250 mg of 5-fluorouracil on days 2 through 5. Drug courses were repeated every 2 weeks and most patients received between 4 and 6 courses. Thirty-five patients with measurable advanced solid cancers entered the study. They consisted of 16 gastric, 5 colorectal, 4 gallbladder, 3 pancreatic, 3 lung, 2 esophageal, 1 uterine, and 1 ovarian cancers. Of the 35 patients, 29 were evaluated for therapeutic effect of the regimen, and the overall response rate was 31.0% (5 CR + 4 PR/29). A 33.3% rate of tumor regression, consisting of 2 complete responses (CR) and 3 partial responses (PR) out of 15 patients (2 CR + 3 PR/15), was seen for gastric cancers. For the other types of tumors the responses were achieved in 2 lung cancers (1 CR + 1 PR/3). 1 uterine cancer (1 CR/1), and 1 ovarian cancer (1 CR/1). The esophageal, colorectal, pancreatic, and gallbladder cancers were unresponsive to this regimen. Toxicities of the drug treatment were clinically tolerable and consisted of general malaise, nausea, vomiting, stomatitis, alopecia, and leucopenia. However, two patients died of uncontrollable metabolic acidosis after 1 and 2 courses, respectively. This intensive course treatment appears to promote the regression of gastric, lung, and gynecologic cancers. PMID- 8452116 TI - Trends in the first ten years of AIDS in New York City. The New York City Department of Health AIDS Surveillance Team. AB - With over 37,000 cases of acquired immunodeficiency syndrome (AIDS) reported by the end of 1991, New York City had reported nearly 20% of all US cases in the first decade of the AIDS epidemic. This report examines cases diagnosed through 1990 and reported through 1991 to describe rates and trends in the affected subpopulations. Case data were collected by the New York City Department of Health AIDS Surveillance Team, using a format standardized by the federal Centers for Disease Control. Deaths attributable to human immunodeficiency virus (HIV) infection were examined using data provided by the New York City Department of Health Bureau of Vital Statistics. From 1981 through 1990, 37,436 cases of AIDS were diagnosed: 83% in men over the age of 19 years, 15% in women over 19, 2% in children under 13, and less than 1% in teenagers aged 13-19. Cumulative rates in New York City adults were as high as 100 per 10,000 in nine neighborhoods. Predominant trends included a sustained plateau in reported incidence in men who reported having sex with men and a continuing rise in cases in injection drug users and women infected through heterosexual intercourse. HIV-related deaths in men, women, and children were continuing to rise at the end of the decade. During the first decade of the AIDS/HIV epidemic, case surveillance in New York City measured the visible portion of the epidemic and provided important data on subepidemics. PMID- 8452117 TI - Perinatal outcome among children of men exposed to lead and organic solvents in the printing industry. AB - The authors investigated the hypothesis that paternal occupational exposures at the time of conception may affect the risk of postconception events by linking records from Oslo, Norway, printers' unions and the Medical Birth Registry of Norway. The linkage yielded 6,251 infants born during the period 1967-1986. On the basis of job classification, fathers were categorized as to their exposure to lead and solvents. Odds ratios were estimated by simple and stratified analysis of tabular data and logistic regression analysis, with children whose fathers were not in lead- or solvent-exposed categories being used as the reference group. In addition, all Oslo births taking place during the same period served as an external reference for computation of standardized morbidity ratios. The adjusted odds ratio for early preterm birth (16-27 weeks) was 5.4 (95% confidence interval (CI) 1.7-17.4) for infants with paternal exposure to solvents and 8.6 (95% CI 2.7-27.3) for children whose fathers were in the lead plus solvents category. The adjusted odds ratio for all perinatal deaths was 2.4 (95% CI 1.2 4.9) for children with fathers in the lead-exposed group and 1.9 (95% CI 0.96 3.7) for children with fathers in the lead plus solvents group. An increased risk of cleft lip was demonstrated, with interaction between sex and paternal exposure to lead: The standardized morbidity ratio for boys in the two subgroups with lead exposure was 4.1 (95% CI 1.8-8.1). Paternal exposure had little impact on birth weight, intrauterine growth, or total number of birth defects. The main problems of the study were the potential for nondifferential misclassification of exposure and the fact that it was not possible to control for potentially confounding life style factors. PMID- 8452118 TI - Indoor air pollution and lung cancer in Guangzhou, People's Republic of China. AB - A case-control study comprising 224 male and 92 female incident lung cancer cases and the same number of individually matched hospital controls was conducted from June 1983 to June 1984 in Guangzhou, People's Republic of China, to evaluate the association between indoor air pollution and lung cancer risk. Guangzhou residents were exposed to several sources of pollution in their homes, most importantly to cooking fumes. Increased risks were found among subjects living in a house without a separate kitchen (the exposure odds ratio was 2.4 (95% confidence interval (CI) 1.4-4.2) for men and 5.9 (95% CI 2.1-16.0) for women). Similarly, living in a house with poor air circulation was associated with an exposure odds ratio of 2.1 (95% CI 1.2-3.8) for men and 3.6 (95% CI 1.4-9.3) for women. A trend in the association between lung cancer risk and factors pertaining to house and kitchen ventilation was observed, and a decreasing risk of lung cancer was observed for several variables indicating better ventilation, even after adjustment for potential confounders such as education, occupation, living area, smoking, and history of chronic respiratory diseases. No statistically significant differences were found between cases and controls for frequency of cooking at home, presence of a chimney in the kitchen, or type of cooking fuel. Smoking was clearly related to risk of lung cancer in both men and women, and among nonsmoking women, exposure to tobacco smoke from their spouses was also associated with an increased risk. These results suggest that, in addition to smoking, indoor air pollution may be a risk factor for lung cancer. PMID- 8452119 TI - A population-based case-control study of dietary factors and endometrial cancer in Shanghai, People's Republic of China. AB - The relation between diet and endometrial cancer was examined in a population based case-control study conducted in Shanghai, People's Republic of China, between 1988 and 1990, involving interviews with 268 cases and 268 controls aged 18-74 years. The subjects' usual dietary intake of 63 major foods during the previous 10 years (disregarding any recent changes) was measured by means of a structured quantitative food questionnaire. Although women in the highest quartile of total caloric intake had a 2.1-fold increased risk of endometrial cancer, risk varied according to the source of calories. The highest quartiles of caloric intake from fat and protein were associated with odds ratios of 3.9 and 3.1, respectively, while calories from carbohydrates, the major contributor of total calories in this population, were not related to risk. The association of fat and protein with endometrial cancer risk was confined to foods of animal origin in the diet. After adjustment for age, body mass index (weight (kg)/height (m)2), and number of pregnancies, odds ratios were 3.5 (95% confidence interval (CI) 2.0-6.0) and 3.0 (95% CI 1.7-5.1) for women in the highest quartiles of intake of animal fat and animal protein, respectively. Food group analyses showed a similar pattern, with high consumption of meat, eggs, and fresh fish being associated with elevated risks. After adjustment for total calories, no significant association of risk was found with intake of vegetables or dark green/yellow vegetables, or with estimated carotene intake, although fruit and allium vegetables were associated with some reduction in risk. These results suggest that diets rich in animal fat and animal protein may play an important role in the etiology of endometrial cancer. PMID- 8452120 TI - Serum antibodies and subsequent cervical neoplasms: a prospective study with 12 years of follow-up. AB - Approximately 40,000 blood samples drawn in 1968-1972 by the Social Insurance Institution's mobile clinic in Finland have been stored. Linking cancer incidence data obtained from the Finnish Cancer Registry with this material yielded 32 cases of cervical cancer diagnosed after drawing of the blood sample. These 32 individuals and 64 matched controls were analyzed for serum antibodies indicative of past infection with Chlamydia trachomatis, Neisseria gonorrhoeae, cytomegalovirus, Epstein-Barr virus, and herpes simplex virus type 2. After adjustment for smoking and other sexually transmitted diseases, antibodies to C. trachomatis showed the strongest association with cervical cancer (odds ratio = 5.0 (95% confidence interval 1.6-15.7)), but the numbers were too small for drawing conclusions as to the sexually transmitted diseases with which cervical cancer is most specifically associated. PMID- 8452121 TI - Does body fatness modify the effect of dietary cholesterol on serum cholesterol? Results from the Chicago Western Electric Study. AB - The hypothesis that lean persons are more responsive than fat persons to the effects of dietary cholesterol was investigated in 1,903 middle-aged employed men who were examined in 1958 and 1959 as participants in the Chicago Western Electric Study. Change in intake of dietary cholesterol was positively associated with change in serum cholesterol for men in the lowest tertile of body mass index (defined as weight (kg)/height (m)2) (< 24.2) but not for men in the highest tertile (> 26.6) after adjustment for change in body mass index and change in intakes of energy and saturated and polyunsaturated fatty acids. A decrease of 150 mg/1,000 kcal in dietary cholesterol was associated with mean changes of 0.46, -0.18, and 0.13 mmol/liter in serum cholesterol for men with body mass indices of < 24.2, 24.2-26.6, and > 26.6, respectively. Body mass index was strongly correlated with subscapular skinfold thickness; thus, these differences in body mass index reflect true differences in adiposity. These results may help to explain inconsistencies that have occurred in feeding experiments with dietary cholesterol, and they suggest that a reduction in dietary cholesterol should have a more favorable effect on the serum cholesterol levels of fat persons after they have lost weight. PMID- 8452122 TI - Abnormal glucose tolerance and alcohol consumption in three populations at high risk of non-insulin-dependent diabetes mellitus. AB - The associations of alcohol intake with the prevalence and incidence of non insulin-dependent diabetes mellitus (NIDDM) and impaired glucose tolerance were examined in three populations at high risk for NIDDM. Population-based surveys performed in Mauritius in 1987, in Kiribati in 1981, and in Nauru in 1982 and 1987 provided data on alcohol intake, glucose tolerance, and associated risk factors for NIDDM in over 8,700 subjects not previously known to be diabetic. There was no consistent relation of alcohol intake to fasting or 2-hour glucose concentration in either prevalence or prospective studies. Odds ratios for newly diagnosed NIDDM associated with increasing alcohol intake were not significantly different from unity in any population in either prevalence or prospective data. Alcohol consumption was, however, related to other metabolic parameters associated with cardiovascular disease and NIDDM, i.e., increased systolic blood pressure, fasting triglycerides, uric acid, and high density lipoprotein cholesterol and a reduction in 2-hour insulin. The results of this study do not support the hypothesis of an independent effect of alcohol consumption on the development of NIDDM, but increased alcohol consumption is associated with variation in other cardiovascular disease risk factors in these three populations. PMID- 8452123 TI - The Beaver Dam Eye Study: the relation of age-related maculopathy to smoking. AB - There are conflicting reports regarding the relation of cigarette smoking to age related maculopathy, a major cause of blindness in the United States. In this report, the authors examined this association in people aged 43-86 years (n = 4,771) who participated in the Beaver Dam Eye Study, Beaver Dam, Wisconsin (1988 1990). Exposure data on cigarette smoking were derived from questions about present and past smoking, duration of smoking, and the number of cigarettes smoked per day. Age-related maculopathy status was determined by grading stereoscopic color fundus photographs using the Wisconsin Age-related Maculopathy Grading System. Smoking status, pack-years smoked, and current exposure to passive smoking were not associated with drusen characteristics (type, area, and confluence) or signs of early age-related maculopathy in any age-sex group studied, except for a higher frequency of increased retinal pigment in males who had ever smoked compared with those who had never smoked. The relative odds for exudative macular degeneration, one form of late age-related maculopathy, in females who were current smokers was 2.50 (95% confidence interval 1.01-6.20) compared with those who were ex-smokers or never smokers; for males, it was 3.29 (95% confidence interval 1.03-10.50). There was no significant relation between smoking status and pure geographic atrophy, another form of late age-related maculopathy. These results suggest that exudative macular degeneration is associated with cigarette smoking and that different forms of macular degeneration may have different etiologies. PMID- 8452124 TI - A prospective study of dehydroepiandrosterone sulfate (DHEAS) and bone mineral density in older men and women. AB - The purpose of this study was to prospectively examine the relation of dehydroepiandrosterone sulfate (DHEAS) to bone mineral density in a community based sample of 260 men and 162 women who were residents of Rancho Bernardo, California. DHEAS levels had been measured in plasma obtained in 1972-1974 when the men were 50-74 years of age and the women were 55-74. In 1988-1991, bone mineral density was measured at the lumbar spine and hip using dual x-ray absorptiometry, and at the mid-radius and ultradistal radius using single photon absorptiometry. Among men, there was a significant decrease in DHEAS levels and bone mineral density at the hip, ultradistal radius, and midshaft radius with increasing age. However, for both men and women, there was no significant association of DHEAS levels with bone mineral density at any site, both before and after adjustment for age, obesity, cigarette smoking, and use of antihypertensive medications. These data do not support the hypothesis of DHEAS having a causal role in senile osteoporosis. PMID- 8452125 TI - Age and season of birth in sudden infant death syndrome in North Carolina, 1982 1987: no interaction. AB - Sudden infant death syndrome (SIDS) is a major cause of death in the postneonatal period. SIDS peaks in the winter and at age 3 months. The hypothesis that season and age interact to determine SIDS survival was tested in race-specific hazards models that included an interaction term for season of birth and survival time. The study population was the 1982-1984 and 1985-1987 North Carolina birth cohorts. The interaction term had null effect in all models, indicating that season and age are independent determinants of SIDS survival. These results may be confounded by exposure to cigarette smoke, for which no data were available. PMID- 8452126 TI - Maternal youth or family background? On the health disadvantages of infants with teenage mothers. AB - The health disadvantages of infants with teenage mothers are well documented. Because poor and minority women are disproportionately represented among teen mothers, differences in infant health by maternal age may reflect family background (pre-childbearing) characteristics rather than the effects of maternal age. To control for differences in family background, the authors compared birth outcomes and maternal behaviors that could affect fetal or infant health among sisters in the US National Longitudinal Survey of Youth (1979-1988). They compared sisters who had first births at different ages in order to study the relation between maternal age and low birth weight, prenatal care, smoking and alcohol use during pregnancy, breast feeding, and well-child visits. The authors found evidence that maternal family background accounts for many of the health related disadvantages of the firstborn infants of teenage mothers. The findings suggest that disadvantaged black primiparous women in their twenties may be an important and possibly underemphasized target population for interventions designed to reduce excess black low birth weight and infant mortality rates. PMID- 8452127 TI - Determination of lung cancer incidence in the elderly using Medicare claims data. AB - The Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute provides data for making national estimates of lung cancer incidence and for monitoring secular trends. The authors compared the number of cases of lung cancer and the incidence rates among elderly residents of the five states included in the SEER program in 1986-1987 with the number of incident cases identified and the rates calculated using hospitalization and enrollment data on elderly Medicare beneficiaries maintained by the Health Care Financing Administration (HCFA) for the same years. The SEER program state registries identified 5.9% more cases than did HCFA (p < 0.01). However, the overall rates were similar (274.2/100,000 population for SEER and 264.7/100,000 population for HCFA), as were the majority of the rates for the different demographic subgroups examined. Age-adjusted lung cancer incidence rates for 1986 through 1990 among elderly Medicare beneficiaries residing outside of all nine SEER areas were 8-13 percent higher than the rates calculated for SEER-area residents. This observation is supported by the existence of similar differences in the age adjusted lung cancer mortality rates for 1979 through 1988 in the same populations. Because the SEER areas may not be representative of the entire nation for lung cancer incidence and HCFA data cover the entire country, the authors recommend using HCFA information to complement the SEER data system. PMID- 8452128 TI - Utility of the National Death Index for ascertainment of mortality among cancer prevention study II participants. AB - This paper reports the results of testing and using the National Death Index to ascertain vital status in the American Cancer Society's prospective cohort study, Cancer Prevention Study II. This cohort of over one million men and women, enrolled by volunteers in 1982, is one of the largest ever to be linked with the National Death Index. In a linkage of over 15,000 persons whose vital status through 1988 had been traced through manual follow-up, 93% of all known deaths were ascertained. Sensitivity varied by demographic factors (race, sex) and availability of identifying information (Social Security number, middle initial). When the Social Security number was available, 97% of known deaths were accurately identified. A computerized matching algorithm was used to minimize manual review of records. With this method, the authors were able efficiently and accurately to reject the many false-positive matches while maintaining a reasonable level of manual record review and death certificate acquisition, thus allowing for continued automated follow-up of this valuable cohort. PMID- 8452129 TI - Alcohol and mortality in Busselton, Western Australia. AB - The authors analyzed 23-year mortality (1966-1989) in 2,171 subjects aged > or = 40 years from a Busselton, Western Australia, prospective study. The analysis revealed significant inverse associations between alcohol consumption and mortality, with trends of decreasing mortality shown from nondrinkers to mild drinkers to moderate drinkers. Compared with nondrinkers, moderate drinkers had an adjusted relative risk of death due to all causes of 0.76 (95% confidence interval (CI) 0.61-0.94). The adjusted relative risk of cardiovascular disease death among moderate drinkers was 0.68 (95% CI 0.51-0.91), and that of coronary heart disease death was 0.66 (95% CI 0.45-0.98). Adjustment for baseline coronary disease risk factors strengthened these trends in the relative risks observed in both women and men. Baseline and follow-up data suggested that 87% of the nondrinkers were long-term abstainers, with 77% having been such for a lifetime. PMID- 8452130 TI - Re: "Nutritional epidemiology of postmenopausal breast cancer in western New York". PMID- 8452131 TI - Re: "Use of electric blankets and risk of testicular cancer" and "Use of electric blankets and risk of postmenopausal breast cancer". PMID- 8452132 TI - Re: "Control for environmental risk factors in assessing genetic effects on disease familial aggregation". PMID- 8452133 TI - RE: "Is abdominal body fat distribution a major explanation for the sex difference in the incidence of myocardial infarction? The study of men born in 1913 and the study of women, Goteborg, Sweden". PMID- 8452135 TI - Farming and prostate cancer mortality. AB - Although farmers appear to be at an increased risk of prostate cancer, the specific exposures which produce the excess risk remain unexplained. This study was based on a retrospectively assembled cohort of male Manitoba, Saskatchewan, and Alberta, Canada, farmers age 45 years or older identified in the 1971 Canadian censuses of population and agriculture. The cohort was linked to the Canadian National Mortality Database using an iterative computer record linkage system for the period June 1971 to the end of 1987. A total of 1,148 prostate cancer deaths and 2,213,478 person-years were observed. Using Poisson regression, the study examined the relation between the risk of dying from prostate cancer and various farm practices as identified on the 1971 Census of Agriculture, including exposure to chickens, cattle, pesticides, and fuels. A weak, but statistically significant, association was found between number of acres sprayed with herbicides in 1970 and risk of prostate cancer mortality. When the analysis was restricted to farmers believed to be subject to the least amount of misclassification, the risk associated with acres sprayed with herbicides increased (rate ratio (RR) = 2.23 for 250 or more acres sprayed; 95% confidence interval (CI) 1.30-3.84; test for trend, p < 0.01). No other farm exposure examined was associated with any detectable pattern of increased or decreased risk. These findings encourage further research to examine the effects of herbicides on prostate cancer. PMID- 8452134 TI - Vasectomy and prostate cancer in US blacks and whites. AB - A large population-based case-control study was carried out to investigate the association between vasectomy and prostate cancer risk in black and in white men in the United States. Study subjects resided in the geographic areas covered by the population-based cancer registries of the Georgia Center for Cancer Statistics, or the Metropolitan Detroit Cancer Surveillance System, or in 10 counties included in the cancer registry of the New Jersey State Health Department. Cases for this study were men aged 40-79 years identified from pathology and outpatient records at hospitals covered by these registries, newly diagnosed with pathologically confirmed prostate cancer between August 1, 1986, and April 30, 1989. Population controls less than age 65 years were selected at periodic intervals by random digit dialing. Older controls were systematically selected (after a random start) from computerized records of the Health Care Finance Administration. A statistically nonsignificant excess risk (odds ratio (OR) = 1.6, 95% confidence interval (CI) 0.5-4.8) for prostate cancer associated with vasectomy was noted in blacks. Overall, the risk for prostate cancer associated with vasectomy in whites was not elevated (OR = 1.1, 95% CI 0.8-1.7). An increase in risk was found, however, for white men who had had a vasectomy 20 years or more prior to study (OR = 1.7, 95% CI 0.9-3.3) or who had had a vasectomy at less than age 35 years (OR = 2.2, 95% CI 1.0-4.4). For the total study group, the odds ratio associated with men who had a vasectomy 20 or more years prior to study was 1.5 (95% CI 0.8-2.7), and the odds ratio associated with men who had had a vasectomy at less than age 35 years was 2.0 (95% CI 1.0-4.0). Further detailed analysis showed that young age at vasectomy (less than age 35 years) was a more important risk factor than was years since vasectomy. PMID- 8452136 TI - Cigarette smoking and the risk of endometrial cancer. AB - A case-control study involving 405 cases of epithelial endometrial carcinoma (newly diagnosed between 1987 and 1990 in five US areas) and 297 population controls enabled evaluation of risk in relation to detailed smoking characteristics. Cigarette smokers were at a reduced risk of disease, with the effect primarily restricted to women whose diseases were detected postmenopausally (relative risk (RR) = 0.6, 95% confidence interval 0.4-0.9). Among postmenopausal women, current smokers showed the greatest reduction in risk (RR = 0.4, 95% confidence interval 0.2-0.7), with former smokers, including those who had recently stopped, being less affected (RR = 0.8). Other measures of smoking were highly correlated with currency of smoking, but there were no clear patterns of risk with either duration or intensity of smoking. Smoking appeared to reduce risk to the greatest extent in subjects who were multiparous, obese, or nonusers of exogenous hormones, but none of these relations was statistically significant. The results support the notion that smoking reduces the risk of endometrial cancer through extraovarian endogenous hormonal mechanisms, but further studies are needed to clarify why reduced risks are most pronounced among postmenopausal women and those currently exposed to cigarette smoke. PMID- 8452137 TI - Association between plasma fibrinogen concentration and five socioeconomic indices in the Kuopio Ischemic Heart Disease Risk Factor Study. AB - The association between five socioeconomic indices (lifetime occupation, education, income, ownership of material possessions, and childhood socioeconomic status) and plasma fibrinogen levels was investigated in middle-aged Finnish men who were part of the Kuopio Ischemic Heart Disease Risk Factor Study. The Kuopio Ischemic Heart Disease Risk Factor Study is based on a representative age stratified sample of 2,682 men aged 42, 48, 54, and 60 years. The data were collected between 1984 and 1989. The present analysis is restricted to the 2,011 men for whom information on fibrinogen and all covariates was available. The covariates were alcohol consumption, body mass index, physical fitness, smoking, coffee consumption, high density lipoprotein cholesterol, low density lipoprotein cholesterol, blood leukocyte count, and prevalent disease (at least one sign of ischemic heart disease, hypertension, diabetes, or previous stroke). An age adjusted inverse association was found between levels of plasma fibrinogen and four of the five socioeconomic indices: current income, education, lifetime occupation status, and current material possessions. After adjustment for the covariates, the association persisted for education, current income, and lifetime occupation. Analysis of the joint effect of childhood and adult socioeconomic status indicated that those who were economically disadvantaged at both times had the highest fibrinogen levels, but the fibrinogen levels of those who were not poor as adults had no variation by childhood socioeconomic status. PMID- 8452138 TI - Secular trends in coronary heart disease mortality in Norway, 1966-1986. AB - In most countries of the western world, the health statistics demonstrate similar secular trends in coronary heart disease mortality. There was a relatively marked increase in the mortality rates until the 1970s, followed by a decline. A cohort analysis was performed to examine these trends. Poisson regression with models that included the effects of age, period, and cohort was applied to Norwegian vital statistics. The results demonstrate that cohort effects explain the secular variations in coronary heart disease mortality in Norway from 1966 to 1986. The author relates these findings to the development of primary and secondary preventive means of coronary heart disease mortality. PMID- 8452139 TI - Prevalence of cardiovascular diseases among older adults. The Cardiovascular Health Study. AB - The Cardiovascular Health Study is a population-based longitudinal study of 5,201 adults aged 65 years and older. Prevalences of myocardial infarction, angina pectoris, congestive heart failure, peripheral artery disease, stroke, and transient ischemic attack were ascertained between June 1989 and May 1990 in participants recruited from Forsyth County, North Carolina; Washington County, Maryland; Sacramento County, California; and Pittsburgh, Pennsylvania. A medical history was taken to obtain self-reports of prevalent disease. For all participants, use of nitrates was ascertained to document angina, electrocardiograms were used to document prevalent myocardial infarction, and ankle-arm blood pressure studies were used to document peripheral artery disease. Self-reports of disease that were not confirmed by examination findings were further investigated by examination of medical records. Reported disease that was confirmed by examination findings or by medical records was classified as "definite." Disease that was documented by examination, but not reported by the participant, was classified as "unreported." The prevalence rates of definite myocardial infarction and angina were 11% and 15%, respectively, among men aged 65-69 years, 18% and 17% among men aged 80-84 years, 4% and 8% among women aged 65-69 years, and 3% and 13% among women aged 80-84 years. Twenty-three percent of men and 38% of women with electrocardiographic evidence of myocardial infarction did not report it. These results suggest that prevalent disease estimates based only on self-report may underestimate the prevalence of cardiovascular diseases in older Americans. PMID- 8452140 TI - Depressive symptoms and headaches in relation to proximity of residence to an alternating-current transmission line right-of-way. AB - Electric power transmission lines have become objects of public controversy. Hypotheses have linked neurobehavioral effects to the electric and magnetic fields that these lines produce. The authors conducted a telephone interview survey in November 1987 to assess the prevalence of depressive symptoms and headache in relation to proximity of residence to an alternating-current transmission line in the United States. Proximity to the line, defined as residing on a property abutting the right-of-way or being able to see the towers from one's house or yard, was positively associated with a measure of depressive symptoms. The association was not explained by demographic variables associated with depression or by attitudes about power lines or other environmental issues. The estimated prevalence odds ratio was 2.8 (95% confidence interval (CI) 1.6 5.1). The estimate did not change appreciably when the definitions of depressive symptoms or of proximity to the line were altered. Nonmigraine headaches had a weaker association with proximity to the line (odds ratio = 1.5, 95% CI 0.76 2.8), and self-reported migraine headaches exhibited no association (odds ratio = 0.99, 95% CI 0.29-3.4). Additional studies of psychological and behavioral measures should be conducted in relation to electric and magnetic fields, with a strong emphasis on improved exposure assessment. PMID- 8452141 TI - Outdoor air temperature and mortality in The Netherlands: a time-series analysis. AB - Death rates become progressively higher when outdoor air temperature rises above or falls below 20-25 degrees C. This study addresses the question of whether this relation is largely attributable to the direct effects of exposure to heat and cold on the human body in general, and on the circulatory system in particular. The association between daily mortality and daily temperatures in the Netherlands in the period 1979-1987 was examined by controlling for influenza incidence, air pollution, and "season"; distinguishing lag periods; examining effect modification by wind speed and relative humidity; and distinguishing causes of death. Important direct effects of exposure to cold and heat on mortality were suggested by the following findings: 1) control for influenza incidence reduced cold-related mortality by only 34% and reduced heat-related mortality by 23% (the role of air pollution and "season" was negligible); 2) 62% of the "unexplained" cold-related mortality, and all heat-related mortality, occurred within 1 week; and 3) effect modification by wind speed was in the expected direction. The finding that 57% of "unexplained" cold-related mortality and 26% of the "unexplained" heat-related mortality was attributable to cardiovascular diseases suggests that direct effects are only in part the result of increased stress on the circulatory system. For heat-related mortality, direct effects on the respiratory system are probably more important. For cold-related mortality, the analysis yielded evidence of an important indirect effect involving increased incidence of influenza and other respiratory infections. PMID- 8452142 TI - Incidence of and risk factors for falls and injurious falls among the community dwelling elderly. AB - To determine the frequency of and risk factors for falls and injurious falls in the noninstitutionalized elderly, the authors conducted a follow-up study of 409 community-dwelling persons aged 65 years or more in west-central Montreal, Quebec, Canada, from May 1987 to October 1988. Following an initial at-home interview, each subject was telephoned every 4 weeks for 48 weeks for collection of data on falls experienced since the last contact. Each of the 12 follow-up interviews was completed by at least 90% of the subjects eligible for interview. Data were also collected in the follow-up interviews on time-varying exposures. Twenty-nine percent of the subjects fell during follow-up; 17.6% fell once, and 11.5% fell two or more times. The incidence rate for falls was 41.4 falls per 1,000 person-months. The majority of falls resulted in no injury or in minor injury only. Potential risk factors investigated included sociodemographic variables, physical activity, alcohol consumption, acute and chronic health problems, dizziness, mobility, and medications. Multivariate analyses showed that the following factors were statistically significantly associated with an increased rate of falls: dizziness (incidence rate ratio (IRR) = 2.0), frequent physical activity (IRR = 2.0), having days on which activities were limited because of a health problem (IRR = 1.8), having trouble walking 400 m (IRR = 1.6), and having trouble bending down (IRR = 1.4). Factors which were protective included diversity of physical activities (IRR = 0.6), daily alcohol consumption (IRR = 0.5), having days spent in bed because of a health problem (IRR = 0.5), and taking heart medication (IRR = 0.6). Risk factors for injurious falls were similar. PMID- 8452143 TI - Malnutrition, cell-mediated immune deficiency, and diarrhea: a community-based longitudinal study in rural Bangladeshi children. AB - A community-based longitudinal study was conducted in Matlab, a rural area of Bangladesh, from May 1988 to April 1989 to examine the associations among malnutrition, cell-mediated immune deficiency, and the incidence of diarrhea in children under age 5 years. A cohort of 705 children was followed for a year; illnesses were ascertained every fourth day by home visits, anthropometric status was evaluated monthly, and cell-mediated immune status was assessed by a multiple antigen skin test at baseline and every 3 months. The diarrhea incidence rate was 4.6 episodes per year. Approximately three quarters of the children were below -2 z score weight for age and height for age, and about a third were below -2 z score weight for height. There was a modest association between undernutrition and the incidence of diarrhea. About 10-20% of the study children were anergic, and these children experienced a 50% increased incidence of diarrhea compared with their immunocompetent counterparts. This association persisted after controlling for the effects of age, nutritional status, socioeconomic status, and history of diarrhea in the previous 3 months. Malnutrition and cell-mediated immune deficiency were important independent risk factors for the occurrence of diarrhea and must both be considered in the design of interventions for the control of this condition. PMID- 8452144 TI - Exposure to children and risk of active trachoma in Tanzanian women. AB - The authors surveyed the trachoma status of 515 women aged 18-60 years and 527 children aged 1-7 years in the trachoma hyperendemic region of Kongwa, Tanzania, in 1989 to further describe the importance of exposure to young children as a risk factor for active trachoma in women. The women were identified as caretakers, who currently cared for children aged 1-7 years; noncaretakers, who lived with, but did not care for, children aged 1-7; or those without children aged 1-7 in the household. The age-adjusted odds ratios for active trachoma seemed to rise with greater exposure to young children, from 1.00 for women without such children, to 1.63 for noncaretakers and 2.43 for caretakers (trend test, p = 0.08). Among those who lived in households with young children, the prevalence of active trachoma in women increased with the total number of young children cared for and with the number of infected children cared for. The prevalence of active trachoma was 40% (6 of 15) for caretakers of three or more infected children, compared with 0 (0 of 88) for caretakers with no infected children (p < 0.0001). Caring for infected children also appeared to be associated with signs of chronic trachoma in caretakers. Noncaretakers who lived with infected children were not at a significantly increased risk for trachoma compared with noncaretakers who were not exposed to such children (5.4% (three of 56) vs. 5.6% (one of 18); p > 0.4). None of the facial signs observed in the children (flies on the face, nasal discharge, etc.) appeared to increase the odds ratio of active trachoma in caretakers beyond the increase associated with trachoma alone in the child. These data support the hypothesis that active disease in women is associated with direct caretaking of young children with active disease. Strategies that interrupt household transmission may affect the binding sequelae of trachoma in women. PMID- 8452145 TI - Evaluation of a method for detecting aberrations in public health surveillance data. AB - The detection of unusual patterns in routine public health surveillance data on diseases and injuries presents an important challenge to health workers interested in early identification of epidemics or clues to important risk factors. Each week, state health departments report the numbers of cases of about 50 notifiable diseases to the Centers for Disease Control and Prevention, and these reports are published weekly in the Morbidity and Mortality Weekly Report. A new analytic method and a horizontal bar graph were introduced in July 1989 to facilitate easy identification of unusual numbers of reported cases. Evaluation of the statistical properties of this method indicates that the results are fairly robust to nonnormality and serial correlation of the data. An epidemiologic evaluation of the method after the first 6 months showed that it is useful for detection of specific types of aberrations in public health surveillance. PMID- 8452146 TI - Antifungal prophylaxis: to prevent or not. PMID- 8452147 TI - Value of liver biopsy in the evaluation and management of chronic liver disease in renal transplant recipients. AB - PURPOSE: Liver disease is a frequent complication in renal transplant recipients. To understand the nature and progression of hepatic disease in these patients, we performed percutaneous biopsies in 77 subjects who had chronic liver dysfunction in the posttransplant period. The purpose of the present investigation is to delineate the morphologic spectrum of chronic liver disease in the renal allograft recipients and to characterize the clinical and histologic progression of each of the different morphologic forms. PATIENTS AND METHODS: Between 1971 and 1990, 915 patients received renal transplants at the Hennepin County Medical Center, Minneapolis, Minnesota. One hundred nineteen (13%) of them had abnormal liver function that persisted for longer than 6 months. Percutaneous liver biopsies were performed in 77 of these patients, but adequate tissue for histologic evaluation was available in only 72. After the biopsy, the clinical and histologic course of each subject was monitored in relation to the baseline hepatic morphology. To assess the predictive value of serum enzymes in diagnosing the histologic lesions, the level of serum enzymes at the time of the biopsy was correlated with the morphologic diagnosis. In addition, several clinical, biochemical, etiologic, and histologic variables were screened for their association with histologic progression to liver cirrhosis. RESULTS: The morphologic diagnosis in the 72 specimens evaluated at baseline was as follows: fat metamorphosis in 8 (11%), chronic persistent hepatitis in 20 (28%), early chronic active hepatitis in 20 (28%), advanced chronic active hepatitis in 15 (21%), and hemosiderosis in 9 (12%). There was no statistical correlation between the serum enzyme levels and the histologic diagnosis. During a mean follow-up of 5.7 +/- 3.9 years, clinical progression to hepatic failure and death occurred in 35% of patients with early chronic active hepatitis, 55% with hemosiderosis, and 60% with advanced chronic active hepatitis. None of the patients with the morphologic diagnosis of fat metamorphosis or chronic persistent hepatitis died as a consequence of hepatic failure. Follow-up liver specimens were obtained in 34 (47%) of the original 72 subjects after a mean interval of 4.5 +/- 4.3 years. Of the 15 patients with the initial diagnosis of early chronic active hepatitis, 9 (60%) showed morphologic transition to advanced chronic active hepatitis, and in 1 of the 5 patients with hemosiderosis (20%), the lesion had resolved after successive phlebotomies. During the follow-up, 60% with early chronic active hepatitis (9 of 14), 66% with hemosiderosis (2 of 3), and 100% with advanced chronic active hepatitis (4 of 4) showed histologic progression to liver cirrhosis. On the contrary, no morphologic alterations were observed in the follow-up specimens of patients with fat metamorphosis or chronic persistent hepatitis. Of the different variables screened for their association with histologic progression, older age at transplant, female sex, and morphologic diagnosis of advanced chronic active hepatitis were found to be significant. CONCLUSION: Histologic diagnosis can be a useful marker in predicting the course of chronic liver disease after renal transplantation. Liver biopsy should be incorporated into the evaluation and management of chronic liver disease in renal transplant recipients. PMID- 8452148 TI - Beta-Lactam antibiotic-induced leukopenia in severe hepatic dysfunction: risk factors and implications for dosing in patients with liver disease. AB - PURPOSE: To determine if an association could be established for leukopenia and administration of beta-lactam antibiotic therapy in patients with hepatic dysfunction. If such an association could be found, to determine the incidence, timing, and risk factors for beta-lactam antibiotic-induced leukopenia. PATIENTS AND METHODS: Patients with hepatic dysfunction, i.e., liver transplant recipients as well as patients with end-stage liver disease awaiting liver transplantation, seen at our institution between October 1989 and October 1991, who received 7 or more days of antibiotics, were studied in a prospective observational fashion. Complete blood count was determined at baseline and followed until the completion of the antibiotic course or until the resolution of leukopenia in leukopenic patients. RESULTS: Leukopenia occurred after a mean of 6 days with 23% of the beta-lactam antibiotic courses as compared with 0% with the non-beta-lactam antibiotic courses (p = 0.046). Development of leukopenia correlated with the severity of liver disease. Patients developing leukopenia had worse synthetic hepatic function as evidenced by a lower serum albumin level (p < 0.01), a lower serum cholesterol level (p < 0.05), and a higher prothrombin time (p < 0.01) as compared with the patients without leukopenia. Leukopenic patients had a lower baseline white blood cell count (p < 0.051) and a lower baseline platelet count (p < 0.01) indicative of a greater degree of hypersplenism. Leukopenic patients received a higher mean daily dosage of cephalosporins as compared with nonleukopenic patients. CONCLUSION: beta-Lactam antibiotics when administered in usually recommended dosages can induce leukopenia in patients with hepatic dysfunction. The probable mechanism is impaired hepatic metabolism of the beta lactam antibiotics resulting in bone marrow suppression of white cell precursors from excessive antibiotic concentrations. The more severe the hepatic dysfunction, the greater the risk. We propose a reduction in dosages of beta lactam antibiotics when used in patients with hepatic dysfunction. Finally, we raise the possibility that this adverse drug effect is more common than currently recognized by physicians. PMID- 8452149 TI - Osteoporosis after cardiac transplantation. AB - PURPOSE: The purpose of this study was to determine the prevalence of osteopenia and fractures and to describe the biochemical indices of mineral metabolism in patients who have undergone cardiac transplantation. PATIENTS AND METHODS: Forty adult patients who had received a cardiac transplant between 1982 and 1990 and who were receiving immunosuppressive therapy with prednisone and cyclosporine A were studied. Bone densitometric measurements by dual-energy x-ray absorptiometry of the lumbar spine and femoral neck and radiographs of the thoracic and lumbar spine were obtained for all patients. Routine serum and urine biochemical values as well as more specialized biochemical analyses (intact parathyroid hormone, metabolites of vitamin D, and osteocalcin) were obtained. RESULTS: Osteopenia was present in 28% of the patients at the lumbar spine and 20% of the patients at the femoral neck. Vertebral fractures were present in 35% of patients. In contrast to other patients receiving glucocorticoids, serum osteocalcin, a marker of bone formation, was elevated in 60% of patients. CONCLUSIONS: Osteopenia and vertebral fractures are common in patients after cardiac transplantation. The presence of elevated osteocalcin levels suggests that the pathogenesis of the osteoporosis in these patients differs from that of glucocorticoid-induced osteoporosis. PMID- 8452150 TI - Cardiogenic shock complicating acute myocardial infarction in patients without heart failure on admission: incidence, risk factors, and outcome. SPRINT Study Group. AB - PURPOSE: Patients with large myocardial infarction (MI) presenting with clinical signs of heart failure are at increased risk for subsequent development of cardiogenic shock and death. Little is known, however, about the development of cardiogenic shock among patients with acute MI presenting without clinical signs of heart failure. The aim of the present study was to examine the incidence, predictors for occurrence, and outcome of in-hospital development of cardiogenic shock among patients with acute MI without heart failure on admission. PATIENTS AND METHODS: Clinical data of 5,839 consecutive patients hospitalized with acute MI were analyzed. RESULTS: Of 3,465 (59%) patients without heart failure on admission (Killip class I), 89 (2.6%) developed cardiogenic shock during their hospital stay. This represented 24% of all cases of in-hospital cardiogenic shock in the entire group. Cardiogenic shock developed more than 24 hours after admission in 66% of cases. All but three patients with cardiogenic shock died whereas a 5% in-hospital mortality was found among patients without cardiogenic shock. Independent predictors for in-hospital shock were age (for a 10-year increment, adjusted relative odds [RO] = 2.45, 90% confidence interval [CI] = 1.50 to 4.02); female gender (RO = 1.51, 90% CI = 0.91 to 2.50); history of angina (RO = 2.64, 90% CI = 1.36 to 3.76); history of stroke (RO = 2.12, 90% CI = 1.26 to 6.35); peripheral vascular disease (RO = 1.99, 90% CI = 0.95 to 4.18); peak lactate dehydrogenase (LDH) greater than four times the normal (RO = 3.16, 90% CI = 1.79 to 5.57); and hyperglycemia on admission (RO = 3.52, 90% CI = 2.13 to 5.84). Patients with six risk factors (excluding LDH values) had an estimated probability of 35% for developing in-hospital cardiogenic shock. CONCLUSIONS: (1) A significant proportion of MI patients who developed cardiogenic shock during hospitalization were free of heart failure on admission. (2) Our study identified several risk factors facilitating early identification of subgroups at risk for cardiogenic shock within otherwise low-risk patients. PMID- 8452151 TI - The febrile parenteral drug user: a prospective study in 121 patients. AB - OBJECTIVE: To determine the most efficient approach to the diagnosis of infective endocarditis (IE) in febrile parenteral drug users (PDUs) and evaluate possible effects of human immunodeficiency virus (HIV) infections or acquired immunodeficiency syndrome (AIDS) on susceptibility to IE and final outcome. DESIGN: A prospective study of appropriate patients admitted on 149 random sampling days during a 14-month period and review of past experience with IE, HIV, and AIDS admissions to hospital. SETTING: An urban university hospital. PATIENTS: Prospectively, 121 febrile PDUs plus an additional 16 found to have IE on nonsampling days during the study period. Retrospectively, all PDUs with IE from 1985 to 1991 and all patients with HIV infections with or without AIDS from July 1990 through December 1991. MEASUREMENTS: Physical examination, hemograms, urinalysis, blood cultures (plus other body fluids when indicated), echocardiography, laboratory testing for HIV status. MAIN RESULTS: Five categories of patients were identified: I. Infective endocarditis (n = 16); II. Other infections with bacteremia (n = 21); III. Bacteremia with unidentified source of infection (n = 14); IV. Infections without bacteremia (n = 52); V. Fever of unknown origin (n = 18). Physical findings and standard laboratory testing did not differentiate Group I from any of the other diagnostic categories. Adding additional IE cases from nonstudy days brought the total to 32. Vegetations were found on echocardiography in 94%; blood cultures, available in 30 of 32 instances, were all positive. HIV or AIDS status was not found to alter susceptibility to IE or influence mortality. While hospital admissions for HIV and especially AIDS have continued to increase among PDUs, the number of cases of IE has decreased since 1988 to 1989. CONCLUSIONS: Based on the high incidence of blood culture positivity and the sensitivity of echocardiography in detecting vegetations in IE, a simple algorithm has been developed for the initial diagnostic management of febrile PDUs admitted with the possible diagnosis of IE. HIV infection, with or without full-blown AIDS, does not appear to affect the incidence or outcome of IE among these patients. Current practices among PDUs may be effecting a decline in IE but not HIV infections. PMID- 8452152 TI - Nosocomial pneumonia in ventilated patients: a cohort study evaluating attributable mortality and hospital stay. AB - PURPOSE: Although nosocomial pneumonia is a common problem in intubated and ventilated patients, previous studies have not clearly demonstrated that nosocomial pneumonia actually results in increased mortality or prolongs hospitalization of these patients. In an attempt to answer these questions, we have performed a cohort study in which patients who developed nosocomial pneumonia and control subjects were carefully matched for the severity of underlying illness and other important variables. PATIENTS AND METHODS: Case patients were 48 ventilated patients with nosocomial pneumonia identified on the basis of results of protected specimen brush quantitative culture and identification of intracellular organisms in cells recovered by bronchoalveolar lavage. For matching cases and their respective controls, the following variables were used: age (+/- 5 years), Simplified Acute Physiologic Score (+/- 3 points), indication for ventilatory support, date of admission, and duration of exposure to risk. RESULTS: Successful matching was achieved for 222 of 240 (92.5%) variables. The mortality rate in cases was 26 of 48 (54.2%) compared with 13 of 48 (27.1%) in controls. The attributable mortality was 27.1% (95% confidence interval [CI], 8.3% to 45.9%; p < 0.01) and the risk ratio for death was 2.0 (95% CI, 1.61 to 2.49). The mean length of stay was 34 days for cases and 21 days for controls (p < 0.02). In the case of pneumonia due to Pseudomonas or Acinetobacter species, the mortality rate was 71.4%, the attributable mortality was 42.8% (95% CI, 14.5% to 69.0%), and the risk ratio was 2.50 (95% CI, 1.31 to 4.61). CONCLUSION: Pneumonias occurring in ventilated patients, especially those due to Pseudomonas or Acinetobacter species, are associated with considerable mortality in excess of that resulting from the underlying disease alone, and significantly prolong the length of stay in the intensive care unit. PMID- 8452153 TI - Multisystem damage associated with tricorporal priapism in sickle cell disease. AB - PURPOSE: Priapism is an uncommon but debilitating complication of sickle cell disease (SCD). Recent observations among adult males regarding the abysmal failure of medical and surgical therapy encouraged us to review our 25-year experience identifying the prognostic features that might determine outcome. PATIENTS AND METHODS: As part of a prospective 25-year longitudinal demographic and clinical cohort study, a subset of 38 (8.2%) patients with priapism were identified among a cohort of 461 men with SCD. The patients with priapism were compared with the nonaffected men with respect to severity of disease expression, hematologic status, beta s globin gene haplotype, and the incidence of sickle related major organ failure. The influence of the treatment modalities on outcome was also evaluated. RESULTS: Priapism occurred as a single episode in 24 patients, and in 14 as temporally clustered repeat episodes. Eighty-seven percent of those with priapism had sickle cell anemia (SS), an increased risk as compared with other variants of SCD (p = < 0.05). There were two distinct age-related patterns of disease expression. Eight patients were prepubertal; they experienced shorter episodes, involvement of the corpora cavernosa only, few recurrent episodes, and a good prognosis for future erectile function. Non-surgical therapy in children was associated with excellent results. In contrast, the 29 postpubertal adults often had involvement of the corpora cavernosa and corpus spongiosa (tricorporal disease) and half had prolonged episodes that lasted longer than 8 days. One pubescent patient had repeated episodes and became impotent. Prolonged or repeated episodes eventuated in impotence in 56%. Surgical intervention was not beneficial. Sickle cell-related organ failure such as stroke, chronic restrictive lung disease, chronic renal failure, and nonhealing leg ulcers was observed more frequently in men who had priapism. Death occurred in nine adult patients (25%) within 5 years of the first episode of priapism. CONCLUSION: Priapism in adult males identifies those at high risk for other sickle cell-related organ failure syndromes and, as such, is another complication indicative of severe disease. The dismal prognosis in SS adults requires better understanding of the precise pathophysiology of low-flow tricorporal priapism. Clarification of the mechanisms inducing the priapic state should lead to specific therapeutic maneuvers and an improved prognosis for this disabling condition. PMID- 8452154 TI - Monoclonal antibodies in cancer detection and therapy. AB - Anticancer antibodies have had a long history in the management of cancer, with major applications having been shown in the immunohistochemistry and immunoassay of tumor-associated antigen markers. With the advent of hybridoma-derived monoclonal antibodies, attempts to use these more reproducible reagents in vivo for cancer detection and therapy have intensified. Radiolabeled monoclonal antibodies appear to be gaining a role in the management of cancer by means of imaging methods to detect sites of increased radioactivity, and several products have been developed and tested clinically. In the area of radioimmunotherapy, a number of problems still need to be solved, including low tumor uptake of the radioimmunoconjugate, dose-limiting myelotoxicity, and the induction of an immune response to repeated doses of murine (foreign) immunoglobulins. Similar problems exist for toxin and drug immunoconjugates, but these also fail to benefit from the "bystander" effect of the ionizing radiation delivered with radioimmunoconjugates, and plant and bacterial toxin molecules appear to have additional immunogenicity that restricts repeated injections. Despite these limitations, recombinant engineering and other chemical approaches are making progress in developing second-generation immunoconjugates that may be more efficacious and less immunogenic as cancer-selective therapeutics. Although nonconjugated, "naked", murine monoclonal antibodies have shown limited success in the therapy of human neoplasms, human and "humanized" forms may be more effective, particularly in lymphatic tumors. Some evidence also suggests that anti-idiotype antibodies (antiantibodies) may serve as surrogate antigens in cancer vaccines. Thus, a number of promising immunologic approaches for cancer diagnosis, detection, and therapy have made important progress in recent years. PMID- 8452155 TI - Methicillin-resistant Staphylococcus aureus: a consensus review of the microbiology, pathogenesis, and epidemiology with implications for prevention and management. AB - Methicillin-resistant Staphylococcus aureus (MRSA) has become a major nosocomial pathogen in community hospitals, long-term-care facilities, and tertiary care hospitals. The basic mechanism of resistance is alteration in penicillin-binding proteins of the organism. Methods for isolation by culture and typing of the organism are reviewed. MRSA colonization precedes infection. A major reservoir is the anterior nares. MRSA is usually introduced into an institution by a colonized or infected patient or health care worker. The principal mode of transmission is via the transiently colonized hands of hospital personnel. Indications for antibiotic therapy for eradication of colonization and treatment of infection are reviewed. Infection control guidelines and discharge policy are presented in detail for acute-care hospitals, intensive care and burn units, outpatient settings, and long-term-care facilities. Recommendations for handling an outbreak, surveillance, and culturing of patients are presented based on the known epidemiology. PMID- 8452156 TI - On professionalism. PMID- 8452157 TI - Fever and abnormal liver function test results in a 56-year-old man. PMID- 8452158 TI - A fatal case of constrictive pericarditis due to a marked, selective pericardial accumulation of amyloid. AB - Distinguishing constrictive pericarditis from restrictive cardiomyopathy, usually due to amyloidosis, is a relatively frequent and difficult diagnostic problem. This report describes, for the first time, a patient with constrictive pericarditis caused by direct, extensive infiltration of the pericardium by amyloid, with only minimal amyloid in the myocardium, and a normal heart weight of 320 g. This patient demonstrates that amyloid may be predominantly deposited in the pericardium and actually cause constrictive pericarditis, as well as simulate its hemodynamic presentation by myocardial deposition. Given a clinical and hemodynamic presentation compatible with either constrictive or restrictive disease, an endomyocardial biopsy or other biopsy revealing amyloidosis does not necessarily rule out pericardial constriction that may be due to amyloid infiltration. The relationship between constrictive pericarditis, seen in this patient, and the other more common manifestations of amyloid heart disease, and the hemodynamic profiles of amyloid cardiomyopathy and constrictive pericarditis are reviewed. PMID- 8452159 TI - Diabetes insipidus, massive polyuria, and hypernatremia leading to permanent brain damage. PMID- 8452160 TI - Kaposi's sarcoma presenting as lymphadenopathy in two HIV-negative elderly patients. PMID- 8452161 TI - Summary statistics and treatment decisions. PMID- 8452162 TI - Primary antiphospholipid syndrome. PMID- 8452163 TI - Randomized double-blind trial of high- and low-dose fleroxacin versus norfloxacin for complicated urinary tract infection. AB - Patients were entered in a double-blind, placebo-controlled, multicenter study to compare low- and high-dose fleroxacin with norfloxacin for the treatment of complicated urinary tract infection (UTI). A total of 296 patients were enrolled; 102, 97, and 97 patients were randomized to receive 200 mg of fleroxacin (low dose), 400 mg of fleroxacin (high-dose), both once daily, or 400 mg of norfloxacin twice daily, respectively, for 10 days. Of these patients, 101, 94, and 95 were included in the safety analysis, and 71, 61, and 58 in the efficacy analysis. The main reason for exclusion from the efficacy analysis was failure to isolate a pathogen at baseline. The groups were comparable with respect to demographics. In the low-dose fleroxacin group, 68 (96%) of 71 patients had bacteriologic cures (eight with superinfection), compared with 56 (92%) of 61 in the high-dose fleroxacin group (two with superinfection) and 52 (90%) of 58 in the norfloxacin group (four with superinfection). Escherichia coli was the most frequent isolate in all groups. In the low-dose fleroxacin group, clinical cure was recorded in 61 (86%) of 71, improvement in six, and failure in four. In the high-dose group, clinical cure was noted in 58 (95%) of 61 patients, improvement in two, and failure in one. In the norfloxacin group, 50 (86%) of 58 patients were clinically cured, four were improved, and four failed. Clinical adverse events were reported by 22 (22%) of 101, 36 (38%) of 94, and 19 (20%) of 95 patients in the low-dose fleroxacin, high-dose fleroxacin, and norfloxacin groups, respectively. Insomnia and nausea were reported most frequently in the fleroxacin groups, and nausea and headache were most common in the norfloxacin group. The efficacy and safety of low-dose fleroxacin are comparable to those of norfloxacin for treatment of complicated UTI. PMID- 8452164 TI - Fleroxacin versus norfloxacin for oral treatment of serious urinary tract infections. AB - Fleroxacin, 400 mg once daily, and norfloxacin, 400 mg twice daily, both administered orally, were compared for the treatment of serious urinary tract infections (UTIs). In total, 301 patients from multiple centers who had serious UTIs were randomized to receive fleroxacin or norfloxacin in a double-blind study. The demographic parameters of the two groups were similar. A total of 190 patients were evaluable for efficacy, 94 in the fleroxacin group and 96 in the norfloxacin group. The reasons for exclusion from the efficacy analysis were not significantly different in the two groups, but more patients receiving fleroxacin were prematurely withdrawn from the study. The majority (134) of the diagnoses were complicated UTI, and the pathogens were primarily Enterobacteriaceae. The clinical responses were cure or improvement in 98% of the fleroxacin group and 92% of the norfloxacin group and failure in 2% of the fleroxacin group and 7% of the norfloxacin group. The bacteriologic results by infection were cure in 98% of the fleroxacin group and 89% of the norfloxacin group (including cure with superinfection in 4% of the fleroxacin group and 5% of the norfloxacin group) and failure in 2% of the fleroxacin group and 11% of the norfloxacin group. Adverse events were more common in the fleroxacin group and were mostly nausea, insomnia, and headache. Fleroxacin, 400 mg once daily, was as effective as norfloxacin, 400 mg twice daily, in eradicating UTIs but was associated with more adverse events. PMID- 8452165 TI - Fleroxacin versus norfloxacin in the treatment of urinary tract infections: a multicenter, double-blind, prospective, randomized, comparative study. AB - In a multicenter, double-blind, prospective, randomized, comparative study, fleroxacin, 400 mg once daily orally, was compared with norfloxacin, 400 mg twice daily orally. Each drug was given for 10 days to study efficacy and safety in the treatment of uncomplicated, recurrent, or complicated urinary tract infection (UTI). A total of 587 patients from 22 centers were enrolled and randomly assigned to fleroxacin (n = 291) or norfloxacin (n = 296). Of these, 163 patients in each group were included in the efficacy analysis, and 287 in the fleroxacin group and 292 in the norfloxacin group were included in the safety analysis. There was no difference between the two groups in terms of bacteriologic or clinical efficacy, with cure rates for each diagnostic subgroup of 93-100% in the fleroxacin group and 91-96% in the norfloxacin group. Superinfection, reinfection, or relapse, as well as development of resistance to the administered drugs, were infrequent and comparable in the two groups. Adverse events were documented in a significantly higher number of patients treated with fleroxacin and involved mainly the digestive system, the central nervous system, and the skin. However, > 90% of such adverse events were judged as mild or moderate in severity and did not lead to premature termination of treatment. Fleroxacin exhibited a clinical and bacteriologic efficacy comparable to that of norfloxacin in this group of patients, with cure rates similar to those of other 4 quinolones, suggesting a promising role for fleroxacin in the treatment of both uncomplicated and complicated UTIs. However, the higher incidence of adverse events with fleroxacin warrants further investigation with special focus on adverse reactions. PMID- 8452166 TI - Fleroxacin versus ofloxacin in patients with complicated urinary tract infection: a controlled clinical study. AB - This prospectively randomized study compared fleroxacin, 400 mg once daily, with ofloxacin, 200 mg twice daily, administered orally for 7-14 days for the treatment of complicated urinary tract infection (UTI) in hospitalized, urologic patients. A total of 80 patients were enrolled in the study. Of these, 30 patients treated with fleroxacin and 35 treated with ofloxacin could be evaluated for therapeutic efficacy. Of the causative organisms, 29 of 30 in the fleroxacin group and 33 of 35 in the ofloxacin group were eliminated. One relapse occurred in the fleroxacin group and two in the ofloxacin group. Reinfection with gram positive isolates was seen in five patients treated with fleroxacin and in one treated with ofloxacin. Thus, the cure rate was 24 (80%) of 30 in the fleroxacin group and 32 (91%) of 35 in the ofloxacin group. In general, both antibiotics were well tolerated. Four patients in the fleroxacin group and five in the ofloxacin group claimed mild, possibly drug-related adverse effects. The treatment of one patient in the ofloxacin group had to be discontinued because of an adverse effect (headache). Both fleroxacin and ofloxacin are effective and well-tolerated antibiotics for the treatment of complicated UTI. PMID- 8452168 TI - A sequential study of intravenous and oral fleroxacin in the treatment of complicated urinary tract infection. AB - This study enrolled patients with complicated urinary tract infections (UTIs) in a trial to determine the efficacy and safety of sequential therapy with intravenous fleroxacin (first 3 days) followed by oral fleroxacin, for a total course of 7-14 days, both administered at a dosage of 400 mg once a day. We enrolled 68 patients with complicated UTIs or acute pyelonephritis, 32 of whom were evaluable for bacteriologic and clinical efficacy. The pathogens isolated included Escherichia coli, 15; enterococci, 9; miscellaneous, 15. Intravenous fleroxacin was given for a mean of 3.2 days, followed by oral fleroxacin for a mean of 5.3 days. A total of 27 patients were clinically cured (84%), two improved, and three failed. A total of 26 patients were bacteriologically cured (81%), and six failed (19%). The bacteria that were not eradicated included enterococci, 4; Staphylococcus epidermidis, 1; and Pseudomonas species, 1. One enterococcal isolate became resistant to fleroxacin. Four patients were bacteremic (E. coli, 3; Proteus mirabilis, 1); the pathogen was eradicated in all cases. Two patients developed urinary enterococcal superinfections. A total of 12 patients experienced 16 adverse reactions remotely, possibly, or probably related to fleroxacin (insomnia, 3; dizziness, 2; miscellaneous, 11). One patient had a grand mal seizure after aspirating gastric contents; the seizure was thought to be only remotely related to the study drug. Fleroxacin was discontinued in two patients because of adverse effects (phlebitis at intravenous access site, 1; anxiety and insomnia, 1). Only minor and asymptomatic laboratory abnormalities were observed. All clinical and laboratory abnormalities resolved with discontinuation of the study drug. Fleroxacin is a safe and effective antibiotic for sequential intravenous and oral treatment of acute pyelonephritis and complicated UTIs. Enterococci may be problematic pathogens, as reported with other fluoroquinolones. PMID- 8452167 TI - Comparison of intravenous fleroxacin with ceftazidime for treatment of complicated urinary tract infections. AB - Intravenous fleroxacin, 400 mg once daily, was compared with intravenous ceftazidime, 0.5-2 g three times a day or 1-2 g twice a day, administered for 4 21 days for treatment of complicated urinary tract infections (UTIs) due to susceptible organisms. Fleroxacin also was tested in an uncontrolled trial. The trial was a multicenter, randomized, open-label study of adults with pyelonephritis or signs and symptoms of UTI and complicating factors. In the controlled trial, 474 patients were randomly assigned in a 2:1 ratio to receive fleroxacin (n = 320) or ceftazidime (n = 154). The microbiologic criterion for diagnosis of UTI was the isolation of > or = 10(5) colony-forming units (CFU) of pathogenic bacteria/mL of urine. The efficacy analyses included 165 fleroxacin treated and 82 ceftazidime-treated patients in the controlled trial and 97 patients in the uncontrolled trial. In the controlled trial, 317 fleroxacin treated and 150 ceftazidime-treated patients were included in the safety analysis. In the controlled trial, the respective rates of bacteriologic cure (< or = 10(4) CFU/mL of urine 48-96 hours after first dose and 2-5 days posttherapy) were 94% (confidence interval [CI], 89-97%) and 95% (CI, 88-99%) in the fleroxacin and ceftazidime groups, and those of clinical cure were 86% (CI, 80 91%) and 89% (CI, 80-95%). Rates of clinical and bacteriologic cure in the uncontrolled study were 95%. In the controlled trial, 9% of the patients in each treatment group experienced one or more adverse events possibly or probably related to the study drug. The percentage of patients terminating therapy prematurely was higher in the fleroxacin than in the ceftazidime group. Once daily dosing with 400 mg of intravenous fleroxacin was equivalent to a standard multidose regimen with respect to rates of bacteriologic and clinical cure in the treatment of complicated UTI. PMID- 8452169 TI - Efficacy of fleroxacin versus amoxicillin in acute exacerbations of chronic bronchitis. AB - In a multicenter study the efficacy and safety of oral fleroxacin at 400 mg once a day and amoxicillin at 500 mg three times daily for 7 days were compared for the treatment of patients with acute bacterial exacerbations of chronic bronchitis due to drug-susceptible bacteria. A total of 194 patients were enrolled, 102 in the fleroxacin group and 92 in the amoxicillin group. Of those enrolled, 22 in the fleroxacin group and 30 (29 for clinical efficacy) in the amoxicillin group were included in the efficacy analysis. All were included in the safety analysis. Clinical success was noted in 21 (95%) of 22 fleroxacin treated patients and 22 (76%) of 29 amoxicillin-treated patients. Bacteriologic cure was obtained in 21 (95%) of 22 of the fleroxacin group and 18 (60%) of 30 of the amoxicillin group. One Haemophilus parainfluenzae strain persisted with fleroxacin. Persisting organisms with amoxicillin included Haemophilus influenzae (four), Haemophilus parainfluenzae (three), Escherichia coli (two), Streptococcus pneumoniae (one), Neisseria species (one), and Proteus mirabilis (one). Adverse events were reported by 41% of 102 patients receiving fleroxacin and 15% of 92 patients receiving amoxicillin. Insomnia, dizziness, and nausea occurred more frequently with fleroxacin. Fleroxacin may be indicated for the treatment of acute bacterial infection in chronic bronchitis known to be due to Haemophilus species and Moraxella catarrhalis. The 92% incidence of resistance among the S. pneumoniae isolates recovered from all enrolled patients suggests that fleroxacin may not be useful for such infections. PMID- 8452170 TI - Fleroxacin versus amoxicillin in the treatment of acute exacerbation of chronic bronchitis. AB - The objective of this double-blind, multicenter study was to compare the efficacy and safety of oral fleroxacin, 400 mg once daily for 7 days, with amoxicillin, 500 mg administered every 8 hours for 7 days, in the treatment of acute exacerbation of chronic bronchitis. Adult male or female inpatients or outpatients were included. Patients gave informed consent and underwent a physical examination. Appropriate sputum specimens were collected, gramstained, and cultured before and 3-9 days after therapy. Complete blood count, serum chemistry, and urinalysis were performed before and 3-9 days after therapy. Of the 625 enrolled patients, 286 (148 in the fleroxacin group and 138 in the amoxicillin group) were evaluable for efficacy. The rate of bacteriologic cure was 96% (142 of 148) among patients in the fleroxacin group and 83% (114 of 138) among patients in the amoxicillin group, showing a statistically significant superiority for fleroxacin. The rate of clinical cure in the patients evaluable for this parameter was 90% (131 of 145) in the fleroxacin group and 82% (111 of 136) in the amoxicillin group. The differences were not significant, but the trend supported the bacteriologic results. Adverse clinical events related to the trial medication were reported by 61 (19%) of 313 patients receiving fleroxacin and by 27 (9%) of 310 patients treated with amoxicillin. The rates of bacteriologic cure and clinical success for fleroxacin were higher than those for amoxicillin. While the overall rate of adverse events was higher in the fleroxacin group, the proportions of patients with severe adverse events was higher in the fleroxacin group, the proportions of patients with severe adverse events were similar in the two groups. Most of the reported events were not serious or severe and were generally well tolerated, as reflected by the low proportion of premature withdrawals for this reason. PMID- 8452171 TI - Intravenous fleroxacin versus ceftazidime in the treatment of acute nonpneumococcal lower respiratory tract infections. AB - Fleroxacin, administered intravenously at a dosage of 400 mg once a day, was compared with ceftazidime, 0.5-2 g three times daily or 1-2 g twice daily, administered for 4-21 days, for treatment of nonpneumococcal lower respiratory tract infections. A total of 319 patients were enrolled and randomized to receive treatment with fleroxacin or ceftazidime in a 2:1 ratio. Of those enrolled, 68 fleroxacin- and 49 ceftazidime-treated patients were included in the efficacy analysis. The most common diagnoses were pneumonia or pneumonitis (47% of the fleroxacin group and 57% of the ceftazidime group) and exacerbation of chronic bronchitis (38% and 33%, respectively). In the fleroxacin group, 59 (88%) of 67 patients were bacteriologic cures, and in the ceftazidime group, 40 (90%) of 49 were bacteriologic cures. It could be concluded with 95% confidence that the bacteriologic outcomes, by infection, for the two groups were equivalent (fleroxacin, 88%; ceftazidime, 90%). The rates of clinical cure were 59 (88%) of 67 for the fleroxacin group and 40 (82%) of 49 in the ceftazidime group, but since the 95% confidence limit around the between-group difference was greater than the stipulated +/- 15%, it could not be concluded that the outcomes were equivalent. The percentage of patients who experienced adverse clinical or laboratory events was similar in the two treatment groups (12% and 13%). The bacteriologic outcomes, by infection, were equivalent for the two treatment groups. Protocol requirements permitting a determination of equivalence of the outcomes for clinical cure were not met, although the rates were similar. PMID- 8452172 TI - Comparison of oral fleroxacin with oral amoxicillin/clavulanate for treatment of skin and soft tissue infections. AB - Oral fleroxacin, 400 mg once a day, and oral amoxicillin/clavulanate potassium (AMX/CP), 400 mg/125 mg three times a day, administered for 4-21 days, were compared for efficacy and safety in the treatment of skin and soft tissue infections. A total of 113 patients were enrolled in a multicenter, randomized, double-blind trial; 57 were assigned to fleroxacin and 56 to AMX/CP. A total of 22 and 33 patients in the fleroxacin and AMX/CP groups, respectively, were evaluable for efficacy. The most common diagnoses were skin abscess (14; 62%) and wound infections (5; 23%) in the fleroxacin group and skin abscess (17; 52%) and skin ulcer (9; 27%) in the AMX/CP group. A total of 20 (91%) of the fleroxacin treated patients and 29 (88%) of the AMX/CP-treated patients were bacteriologically cured (two fleroxacin- and one AMX/CP-treated patients developed super-infection). The eradication rate for Staphylococcus aureus was 100% (11 of 11) in the fleroxacin group and 89% (17 of 19) in the AMX/CP group; 18 (82%) of the fleroxacin group and 25 (76%) of the AMX/CP group were clinically cured. Adverse events were seen in 22% (12 of 54) of the fleroxacin group and 25% (13 of 53) of the AMX/CP group. None were serious. Bacteriologic and clinical cure rates and safety results for the two groups were similar. The small sample size precluded statistical analysis at the 95% confidence level. PMID- 8452173 TI - Open trial of oral fleroxacin versus amoxicillin/clavulanate in the treatment of infections of skin and soft tissue. AB - In a multicenter, prospective, randomized trial, fleroxacin was compared with amoxicillin/clavulanate potassium (AMX/CP) for the treatment of infections of skin and soft tissue. Fleroxacin was given at a dosage of 400 mg once daily, and AMX/CP was given at a dosage of 500 mg/125 mg three times a day. Each was administered for 4-21 days. Adult patients with the clinical diagnosis of skin or soft tissue infections were eligible for enrollment. Patients were randomized in a 2:1 ratio. A total of 191 patients were enrolled; 126 took fleroxacin, and 65 took AMX/CP. Of these patients, 42 in the fleroxacin group and 26 in the AMX/CP group were evaluable for both clinical and bacteriologic efficacies. Patients with abscesses comprised the largest single category in each group. Principle reasons for exclusion included: patients lost to follow-up (17 [13%] fleroxacin, 12 [18%] AMX/CP); failure to isolate a causative pathogen (19 [15%] fleroxacin, 9 [14%] AMX/CP); and resistance to study drug (11 [9%] fleroxacin, 2 [3%] AMX/CP). Staphylococcus aureus was the most commonly isolated pathogen. Streptococcus group A, Staphylococcus coagulase-negative, Escherichia coli, and Proteus species, in decreasing order, were the next most common pathogens. Clinical and bacteriologic efficacy was excellent in both groups, with a cure rate of > or = 90%. There were two bacteriologic failures in each group. Patients taking fleroxacin complained of slightly more adverse events, which involved primarily the digestive and central nervous systems. The rate of withdrawal from the study because of adverse events was 4% in both groups. Fleroxacin, 400 mg given once daily, is safe and as effective as AMX/CP in the treatment of skin and soft tissue infections in adults. PMID- 8452174 TI - Comparative efficacy and safety of oral fleroxacin and amoxicillin/clavulanate potassium in skin and soft tissue infections. AB - The objective of this open-label, randomized, multicenter study was to compare the efficacy and safety of fleroxacin, 400 mg administered orally once daily, and amoxicillin/clavulanate potassium (AMX/CP), 500 mg/125 mg administered orally three times daily, for 4-21 days to patients with skin and soft tissue infections (SSTIs). The specific diagnoses in both groups were primarily skin abscess, impetigo, and skin ulcer, as well as wound infection erysipelas, folliculitis, cellulitis, and lymphangitis. A total of 285 patients were randomized to treatment in a 2:1 ratio, 190 in the fleroxacin group and 95 in the AMX/CP group. Adult male or female inpatients or outpatients were included in the trial and were followed up after 3-5 days of therapy and 3-9 days after completion of therapy for assessment of bacteriologic, clinical, and safety parameters. The most frequently isolated pathogen in both treatment groups was Staphylococcus aureus. Bacteriologic cures were observed in 87 (76%) of 115 evaluable patients in the fleroxacin group and in 41 (72%) of 57 evaluable patients in the AMX/CP group. Clinical cure was seen in 86 (75%) of 114 patients in the fleroxacin group and 45 (79%) of 57 patients in the AMX/CP group. Clinical adverse events related to the trial medication were reported by 40 (21%) of 189 patients in the fleroxacin group and by 16 (17%) of 95 patients in the AMX/CP group. In both groups, most adverse events were mild or moderate in severity and involved the digestive system (primarily diarrhea, nausea, and vomiting). In the fleroxacin group, adverse events affecting the central nervous system (mainly dizziness, insomnia, somnolence) also were reported. In this study, both fleroxacin and amoxicillin/clavulanate potassium were effective and well tolerated in the treatment of skin and soft tissue infections. PMID- 8452175 TI - Systemic antimicrobial therapy for skin and skin structure infections: comparison of fleroxacin and ceftazidime. AB - Intravenous fleroxacin, 400 mg once a day, was compared with ceftazidime, 0.5-2 g three times a day or 1-2 g twice a day, for the treatment of skin and skin structure infections. Duration of treatment was 4-21 days. The study was a multicenter, unblinded comparison. Of the 316 patients enrolled, 212 were randomized to treatment with fleroxacin and 104 to ceftazidime (2:1 ratio); 92 fleroxacin-treated patients and 50 ceftazidime-treated patients were included in the standard analysis of efficacy. The most common diagnoses were wound infections and cellulitis, which affected 36% and 30% of the fleroxacin group, and 24% and 24% of the ceftazidime group, respectively. In the fleroxacin group, 82% of the infecting organisms were eradicated, and in the ceftazidime group, 79%. The overall rates of bacteriologic cure, by infection, were 79% for the fleroxacin group and 74% for the ceftazidime group, and those for clinical cure were 82% and 73%, respectively. It could not be concluded with 95% confidence that the two regimens resulted in equivalent cure rates because the range of between-group differences was outside the stipulated limits of +/- 15%. The percentage of patients with one or more adverse events was approximately twice as high (17% vs. 9%) in the fleroxacin group than in the ceftazidime group. The most frequent event in both groups was nausea. In this study, intravenous therapy with fleroxacin or ceftazidime produced similar bacteriologic and clinical cure rates, but the statistical requirements permitting a conclusion of equivalence at protocol levels were not met. PMID- 8452176 TI - Efficacy of oral fleroxacin in bone and joint infections. AB - Bone and joint infections have traditionally required long-term parenteral antimicrobial therapy, which is often expensive and inconvenient. Because of their excellent absorption and tissue penetration, oral quinolones may provide an alternative to parenteral therapy. This multicenter study was designed to evaluate the efficacy and safety of oral fleroxacin in osteomyelitis and septic arthritis. A total of 96 patients with either septic arthritis or acute or chronic osteomyelitis from 17 U.S. centers were enrolled in a noncomparative study using oral fleroxacin 400 mg per day. Patients with implantable devices were excluded. Proof of infection for evaluability required clinical findings in addition to bacteriologic recovery of a susceptible organism from synovial fluid or bone. Treatment lasted 2-12 weeks. Clinical and bacteriologic outcomes were judged at the conclusion of therapy and in the 6-week follow-up period. A total of 30 patients qualified for efficacy analysis (26 osteomyelitis, 4 septic arthritis). Bacteriologic cure was achieved in 77% of the osteomyelitis group and 50% of the septic arthritis group. Clinical cures were reported in 54% of the osteomyelitis group and 50% of the septic arthritis group. Staphylococcus aureus was the most frequently recovered pathogen (62% evaluable cases). Safety was evaluated in 96 patients. The most common side effects were nausea, vomiting, and skin reactions. Oral fleroxacin may be a safe, effective, and certainly less expensive alternative to standard intravenous antimicrobial therapy in patients with bone and joint infections. PMID- 8452178 TI - Efficacy and toxicity of fleroxacin in the treatment of travelers' diarrhea. AB - The efficacy and safety of fleroxacin in brief self-treatment of travelers' diarrhea were studied. In The Gambia, 195 tourists with acute diarrhea were randomized in a double-blind, controlled trial into three treatment groups: fleroxacin 400 mg for 1 day, fleroxacin 400 mg daily for 2 days, and placebo. Microbiology of stools was assessed only at recruitment. In the fleroxacin treated groups, stool consistency was normal in 67% and 71% of the volunteers after 48 hours, as compared to 37% in the placebo group (p < 0.01). The time to total relief of diarrhea and of all symptoms was also significantly shorter in fleroxacin-treated patients. Adverse events, particularly slight neuropsychiatric reactions (headache, insomnia) were more frequent in the fleroxacin-treated groups (p < 0.05). There was no statistically significant difference in efficacy and tolerance if fleroxacin was administered for 1 or 2 days. A single dose of fleroxacin 400 mg may be recommended for the self-treatment of travelers' diarrhea. PMID- 8452177 TI - A pilot study of oral fleroxacin given once daily in patients with bone and joint infections. AB - The object of this open-label, noncomparative, multicenter study was to evaluate the efficacy and safety of 400 mg of fleroxacin administered orally once daily for 2-12 weeks to patients with bone and joint infections (osteomyelitis, septic arthritis, and prosthetic joint infection). A total of 90 adult patients (56 men and 34 women) were treated at 11 centers. Patients returned on days 5-9 of treatment, subsequently every 2 weeks during treatment, and 0-3 days and 28-42 days (compulsory follow-up) after treatment for assessment of bacteriologic, clinical, and safety parameters. A total of 19 patients (13 with osteomyelitis, 5 with septic arthritis, and 1 with prosthetic joint infection) were bacteriologically evaluable. Staphylococcus aureus was the predominant pathogen isolated in all evaluable infections. Of the 13 patients with osteomyelitis, 11 (85%) were bacteriologically cured and 10 (77%) were clinically cured. Three of the five patients with septic arthritis and the single patient with a prosthetic joint infection were both bacteriologically and clinically cured. Clinical adverse events related to fleroxacin were reported by 25 (28%) of the 90 patients. Most of these events involved the digestive system (primarily constipation and nausea) and the central nervous system (primarily insomnia and headache). The majority of these were of mild or moderate intensity and occurred during the first 2 weeks of treatment. Adverse events led to premature discontinuation of treatment in seven patients. Bone and joint infections continue to represent a therapeutic challenge. Treatment is based mainly on surgical procedures (drainage, sequestrectomy, ablation of implants, and implantation of cement impregnated with antibiotics) and on parenteral administration of antibiotics, requiring hospitalization of the patient. Fleroxacin, a new fluoroquinolone, has proven in vitro activity against bacteria involved in bone and joint infections. Its oral, once-daily administration, which eliminates hospitalization and its attendant costs, makes this drug an effective outpatient treatment of bone and joint infections. PMID- 8452179 TI - Treatment of acute bacterial diarrhea: a multicenter international trial comparing placebo with fleroxacin given as a single dose or once daily for 3 days. AB - This study was designed to test the efficacy of 400 mg fleroxacin given orally as a single dose or once daily for 3 days against acute bacterial diarrhea. A group of 508 adults with acute diarrhea were entered into a randomized, double-blind, placebo-controlled, multicenter trial. Patients were examined and asked about numbers of liquid stools daily for 3 days and at 5 days after start of treatment. Repeat stool samples were obtained for culture on days 3 and 5 after start of treatment. A total of 332 patients showed stool cultures positive for bacterial pathogens sensitive to fleroxacin and completed their treatments. Patients treated with fleroxacin, both single-dose and 3-day regimens, showed faster clinical improvement than did placebo-treated patients, as shown by earlier cessation of diarrhea (p < 0.001) and reduction in mean number of loose stools per day on days 2, 3, and 5 after start of therapy (p < 0.05). Bacteriologic efficacy was demonstrated by negative stool cultures for initial pathogens on days 3 and 5 after start of therapy in 94% of patients treated with single doses of fleroxacin and in 93% of patients treated with three doses of fleroxacin as compared with 57% of patients treated with placebo (p < 0.001). Patients with cholera, shigellosis, and infections due to Vibrio parahaemolyticus showed both clinical and bacteriologic responses to fleroxacin treatment, whereas patients with salmonellosis showed only bacteriologic responses. The good overall clinical and bacteriologic responses of most patients with acute bacterial diarrhea of fleroxacin indicate that this convenient single-dose therapy should be advantageous for empiric treatment of certain diarrheal illnesses. PMID- 8452180 TI - Randomized comparative study of fleroxacin and chloramphenicol in typhoid fever. AB - This study compared fleroxacin, 400 mg daily for 7 or 14 days, with chloramphenicol, 50 mg/kg per day for 14 days, for the treatment of patients with typhoid fever in a multicenter study. A total of 184 patients were randomly assigned to the three treatment groups. Efficacy was determined by culture of blood and stool, overall clinical response, and time to defervescence. Safety was assessed by occurrence of adverse events and laboratory abnormalities. A total of 97 patients were evaluable for efficacy, 28 in the fleroxacin 7-day group, 35 in the fleroxacin 14-day group, and 34 in the chloramphenicol group. All showed rapid defervescence with high cure rates. Bacteriologic cure rates were 96% in the fleroxacin 7-day group, 97% in the fleroxacin 14-day group, and 85% in the chloramphenicol group. Clinical cure rates were 83-100% with fleroxacin and 82% with chloramphenicol. The time to defervescence was shorter for patients treated with fleroxacin than for those treated with chloramphenicol. All three treatment regimens were well tolerated. Fleroxacin, 400 mg daily for 7 days, appears to be satisfactory for the treatment of typhoid fever and compares favorably with the standard 14-day therapy with chloramphenicol. PMID- 8452181 TI - Safety of fleroxacin in clinical trials. AB - This article reviews the safety of fleroxacin in clinical trials. Data from 4,450 patients treated with oral fleroxacin and 650 treated with intravenous fleroxacin were analyzed. The overall rate of adverse reactions for patients treated with oral fleroxacin was 20% for those given 200 mg daily and 20% for those given a daily dose of 400 mg. The adverse reaction rate with the intravenous formulation was 20%. The most frequent adverse reactions involved the gastrointestinal tract (11%) and the central nervous system (9%). All events were reversible. Insomnia was the most commonly reported adverse event. The safety profile of fleroxacin was similar to that reported with other fluoroquinolones. PMID- 8452182 TI - Therapeutic efficacy of fleroxacin for eliminating catheter-associated urinary tract infection in a rabbit model. AB - The efficacy of fleroxacin as therapy for experimentally induced catheter associated urinary tract infection (CAUTI) was examined. A rabbit model of CAUTI using a closed urinary catheter drainage system and the mutant strain of Escherichia coli (WE 6933) were used to examine three dosage regimens (30 mg/kg q8h i.v.; 20 mg/kg q8h i.v.; and 10 mg/kg q8h++i.v.) of fleroxacin administered intravenously for 4 days. Quantitative bacterial counts, urinary concentrations of fleroxacin and desmethylferoxacin, histopathologic changes, and electron microscopic evaluation of catheter-associated biofilm and mucosal biofilm were performed. The results indicated that the bacterial biofilm on the urinary catheter could be eliminated by fleroxacin at 30 mg/kg q8h i.v. and 20 mg/kg q8h i.v. Fleroxacin concentrations in urine exceeded the levels necessary to destroy E. coli. Viable bacteria were eliminated with the third regimen (10 mg/kg q8h i.v.), but electron microscopy demonstrated remnants of bacterial biofilm. Histopathologic changes were significantly reduced in all fleroxacin-treated rabbits, and scanning electron microscopy showed deterioration of the bacterial biofilm on the surface of the Foley catheter in treated animals. These data suggest that fleroxacin may be useful for treating catheter-related infections because these therapeutic dosages limited ascending infections of the urethra and bladder, eliminated catheter-associated biofilms, and killed planktonic bacteria in urine. PMID- 8452183 TI - Pharmacokinetics of fleroxacin as studied by positron emission tomography and [18F]fleroxacin. AB - A new method of tracing the disposition of fleroxacin was tested in infected and noninfected animals in an effort to develop a technique that might be applicable in humans. [18F]fleroxacin was synthesized and shown to be identical physically, chemically, and in its antimicrobial activity to the commercially produced product. Tracer amounts of [18F]fleroxacin were coinjected with a pharmacologic dose of unlabeled drug (10 mg/kg) into normal mice, rats with focal thigh infection due to Escherichia coli, and normal and infected rabbits. The rats and mice were killed at fixed time intervals after injection, and the concentration of drug was determined by radioactive counting in a well-type counter; the rabbits were studied both by this method and by positron emission tomographic (PET) imaging. These studies validated the reliability of the new approach and suggested that it could be applied safely to humans. In all three animal species studied, delivery of [18F]fleroxacin to most tissues was rapid, with the notable exception of the brain. Accumulation of drug in infected thigh muscle was similar to that in normal muscle. The concentrations of drug reached in various tissues suggest that fleroxacin will be particularly useful in the treatment of gastrointestinal, urinary tract, hepatobiliary, and skeletal infections and that it shows promise for the treatment of lung and soft tissue infection. The minimal concentrations of drug delivered to the brain should decrease the occurrence of central nervous system toxicity with this particular fluoroquinolone. PMID- 8452184 TI - Overview of the pharmacokinetics of fleroxacin. AB - The pharmacokinetic properties of fleroxacin in relation to other quinolones are presented. Fleroxacin, like all quinolones, is well absorbed, reaching peak concentrations within 2 hours. Interactions with Ca2+ and Al3+ are minimal and possibly of little clinical importance. The drug is eliminated via filtration in the kidney. It is therefore sensitive to changes in renal function. Accumulation of drug in the body is minimal, and change from intravenous to oral dosing results in nearly identical serum concentrations. Aside from the modest effect of metals on its absorption, fleroxacin does not interact/compete with substances oxidized in the liver, such as theophylline, and drug interactions are minimal. Its long serum half-life (8-12 hours) allows once-a-day dosing. This feature, along with its modest drug interactions, makes fleroxacin an attractive quinolone, at least with respect to its pharmacokinetics. PMID- 8452185 TI - Pharmacokinetics of fleroxacin in renal impairment. AB - Fleroxacin is excreted primarily via the kidneys in its unchanged form, and therefore renal impairment has a major influence on the pharmacokinetics of this drug. This study examined the pharmacokinetics of oral and intravenous fleroxacin in patients with renal impairment. Patients with renal disease (mean glomerular filtration rate [GFR], 22 mL/min) and healthy subjects (mean GFR, 100 mL/min) received 400 mg of fleroxacin orally and 100 mg of fleroxacin intravenously in a crossover design. Serial blood samples and a complete urine collection were obtained for > or = 72 hours after dosing. Unchanged drug in plasma and urine was determined by reverse-phase high-performance liquid chromatography. Fleroxacin was well tolerated by all study participants. Renal impairment had no influence on the complete absorption of fleroxacin from the gastrointestinal tract, the maximal plasma concentration, and the steady-state volume of distribution (Vd-ss > 1 L/kg). However, systemic clearance in patients was significantly decreased (p < 0.05) to 44.4 mL/min compared with 87.1 mL/min in healthy subjects. This decrease could be ascribed to a reduction in renal clearance from 59.1 mL/min in healthy subjects to 8.8 mL/min in patients. Metabolic clearance was not reduced significantly. As a consequence of reduced clearance, the mean elimination half life in patients increased from 13.6 hours to 21.4 hours and the area under the concentration-time curve from 87.0 mg.h/L to 170.5 mg.h/L. To avoid an unacceptable accumulation of fleroxacin in the body during multiple dosing, the following dose adjustment was recommended: patients with renal disease whose GFR is < 40 mL/min should receive the normal loading dose, i.e., 400 mg, but should receive maintenance doses that are reduced by 50%, i.e., to 200 mg. PMID- 8452186 TI - Penetration of fleroxacin into body tissues and fluids. AB - Concentrations of fleroxacin in human body fluids and tissues were studied to obtain information about the efficacy of the drug at the site of infection and the ratio of fleroxacin concentrations in tissue or fluid versus those in plasma as a measure of the extent of penetration. Samples of body fluids and tissues were obtained at various intervals after oral administration, and fleroxacin concentrations were determined by high-performance liquid chromatography. After administration of the standard dose of 400 mg once daily, the maximal plasma concentrations were 5-7 mg/L at steady-state and the minimal concentrations were approximately 1 mg/L at the end of the dosing interval. In most biologic specimens, such as myometrium, fallopian tube, bile bladder wall, bone, tonsils, maxillary sinus mucosa, prostatic adenoma, sputum, inflammatory fluid, synovia, lymph, saliva, and tears, the levels of fleroxacin were similar to those in plasma. In bile, nasal secretions, seminal fluid, lung, bronchial mucosa, and ovaries, the drug concentrations were 2-3 times higher than those in plasma. Penetration of fleroxacin into fat, lens, bronchial secretions, sweat, and aqueous humor was limited, with drug levels reaching only 10-40% of the concomitant levels in plasma. The measured concentration ratios did not vary markedly with time, and the decline in drug concentrations in tissues and fluids was generally parallel to that in plasma. The breakpoint for susceptibility is 1 micrograms/mL. The susceptibility breakpoint was exceeded by the drug concentration in plasma for the entire dosing interval and was also reached or exceeded in most body tissues and fluids. PMID- 8452187 TI - Multicenter trial of fleroxacin versus ceftriaxone in the treatment of uncomplicated gonorrhea. AB - In a multicenter, randomized, open, comparative trial, patients with uncomplicated gonorrhea were treated with 400 mg of oral fleroxacin or 250 mg of intramuscular ceftriaxone. A total of 458 men and 447 women were enrolled. Of these, 312 men (68%) and 245 women (55%) were evaluable for efficacy. The treatment groups were demographically similar. Among evaluable men, fleroxacin eradicated 154 of 155 (99%; 95% confidence interval [CI]: 98.1-100%) urethral and 2 of 2 pharyngeal infections, while ceftriaxone eradicated 156 of 156 (95% CI: 99.4-100%) urethral and 5 of 5 pharyngeal infections. Among evaluable women, fleroxacin eradicated 127 of 128 (99%; 95% CI: 97.7-100%) cervical, 20 of 20 anorectal, 16 of 16 urethral, and 7 of 7 pharyngeal infections, while ceftriaxone eradicated 108 of 108 (95% CI: 99.1-100%) cervical, 24 of 24 anorectal, 25 of 25 urethral, and 9 of 9 pharyngeal infections. Adverse events were reported by 68 (16%) of 426 subjects in the fleroxacin group and 20 (5%) of 380 in the ceftriaxone group (p < 0.0001). The most common adverse events reported by the patients who received fleroxacin were nausea (5%), headache (3%), and vaginitis (3%). One patient had severe vomiting, 19 participants had adverse reactions classified as moderate, and 48 patients had mild adverse reactions. Fleroxacin was highly effective in the treatment of uncomplicated gonorrhea and represents an oral alternative to ceftriaxone. Adverse events were more common with fleroxacin than with ceftriaxone. PMID- 8452188 TI - Fleroxacin in the treatment of chancroid: an open study in men seropositive or seronegative for the human immunodeficiency virus type 1. AB - Fleroxacin was prescribed to treat both HIV-negative and HIV-positive men with proven chancroid in an open study. HIV-negative men were treated with a single 400-mg dose of fleroxacin, and HIV-positive men were treated with 400 mg daily for 5 days. Three of the 58 evaluable HIV-negative men were clinical and microbiologic failures, and two of the 22 evaluable HIV-positive men had persisting infection with Haemophilus ducreyi. Both regimens were well tolerated. Fleroxacin is an acceptable alternative to existing treatment regimens for chancroid in men. PMID- 8452189 TI - Multicenter study of single-dose and multiple-dose fleroxacin versus ciprofloxacin in the treatment of uncomplicated urinary tract infections. AB - The clinical efficacy and safety of single-dose and multiple-dose fleroxacin were assessed and compared with those of ciprofloxacin in women with uncomplicated urinary tract infection (UTI) in this clinical study. This multicenter, randomized, double-blind, prospective study compared single-dose therapy with fleroxacin, 400 mg, with 7-day courses of fleroxacin, 200 mg once a day, and ciprofloxacin, 250 mg twice a day, in the treatment of uncomplicated symptomatic UTI in women at 18 centers in the United States. Of 961 patients enrolled, 316 were in the fleroxacin single-dose group, 321 in the fleroxacin 7-day group, and 324 in the ciprofloxacin group. Of these patients, 943 met the criteria for inclusion in the safety analysis and 556 met those for inclusion in the efficacy analysis. Bacteriologic cure rates at 5-9 days after therapy in patients evaluable for efficacy were 88%, 96%, and 96% in the single-dose fleroxacin group, 7-day fleroxacin group, and 7-day ciprofloxacin group, respectively (p < 0.05). Clinical cures occurred in 93.6%, 97.2%, and 98% of the groups, respectively (difference not significant). At 4-6 weeks after therapy, the rates of bacteriologic cure in the single-dose fleroxacin group, 7-day fleroxacin group, and 7-day ciprofloxacin group were 91%, 89%, and 93%, respectively (difference not significant). Adverse events were similar to those with other new quinolones and comparable among the treatment groups. Insomnia was more frequent in patients who received fleroxacin. Fleroxacin and ciprofloxacin as multidose regimens are similarly safe and effective in the treatment of uncomplicated UTI in women. Single-dose fleroxacin achieved a clinical response rate comparable to that achieved by the multiple-dose regimens, whereas its bacteriologic eradication rate was inferior. PMID- 8452190 TI - In vitro activity of fleroxacin in combination with other antimicrobial agents. AB - The trifluoroquinolone fleroxacin inhibits the majority of Enterobacteriaceae at concentrations < or = 1 micrograms/mL and most Pseudomonas aeruginosa and staphylococci at < or = 2 micrograms/mL. The purpose of this study was to determine the effect of the combination of fleroxacin with other antimicrobial agents. Previous studies that used checkerboard assay, fixed concentrations, and killing curves were reviewed, and these methods were used to evaluate the combination of fleroxacin and agents that had not been previously studied. The combination of fleroxacin with such aminoglycosides as gentamicin, amikacin, and tobramycin is indifferent against most Enterobacteriaceae, as is the combination of fleroxacin with penicillins, cephalosporins, rifampin, clindamycin, and metronidazole. Combinations of fleroxacin with penicillins, cephalosporins, imipenem, aminoglycosides, clindamycin, metronidazole, and rifampin are indifferent against P. aeruginosa. Fosfomycin and fleroxacin acted synergistically against P. aeruginosa. Against staphylococci, combinations of fleroxacin with oxacillin, rifampin, or fosfomycin had synergistic or additive effects, whereas combinations of fleroxacin with vancomycin, gentamicin, or metronidazole have shown indifference. No synergy or antagonism has been found for combinations of fleroxacin with penicillin, vancomycin, erythromycin, clindamycin, or rifampin against streptococci or enterococci. The combination of fleroxacin and metronidazole has proved synergistic against various Bacteroides species. In general, combinations of fleroxacin with other antimicrobial agents display indifference and rarely synergy. Thus, fleroxacin can be combined with other antibiotics to enlarge the spectrum of activity. PMID- 8452191 TI - Comparison of fleroxacin and amoxicillin in the treatment of uncomplicated urinary tract infections in women. AB - Fleroxacin, 400 mg, was compared with amoxicillin, 3,000 mg, each administered orally in a single dose, for the treatment of women with acute uncomplicated symptomatic urinary tract infections. A total of 142 patients were randomized to receive fleroxacin, and 147 patients to receive amoxicillin. Of these, 33 in the fleroxacin group and 39 in the amoxicillin group were considered bacteriologically evaluable. Cure at 5-9 days after treatment was achieved in 32 (97%) of the fleroxacin-treated patients and in 22 (56%) of the amoxicillin treated patients (p < 0.001). For the most frequently isolated pathogen (Escherichia coli), all 24 isolates were eradicated in the fleroxacin group, as were 11 of 25 in the amoxicillin group. At 6 weeks after therapy, bacteriologic cure was maintained in 20 (95%) of the 21 evaluable patients who received fleroxacin and in 8 (89%) of 9 evaluable patients who received amoxicillin. There were no reinfections in either group. A total of 280 patients were assessed for safety. Clinical adverse events were reported in 32 (23%) of 137 patients in the fleroxacin group and in 19 (13%) of the 143 patients in the amoxicillin group. In both groups, the most common adverse effects were gastrointestinal, while adverse events involving the central nervous system were more frequent in patients who received fleroxacin. On the basis of this study, it appears that fleroxacin is demonstrably more effective than amoxicillin as single-dose therapy for uncomplicated urinary tract infection. PMID- 8452192 TI - Effect of chronic ethanol on the septohippocampal system: a role for neurotrophic factors? AB - The mechanisms by which chronic ethanol exposure produces neuronal damage have not been established. Potentially ethanol may reduce normal neurotrophic influences necessary for neuronal survival, growth, and function. We hypothesized that chronic ethanol exposure might produce a decrease in the synthesis, availability, upregulation, delivery, and/or the biological activity of normally occurring neurotrophic factors, or may alter the capacity of target neurons to respond to these factors. The available evidence leading to this hypothesis and supporting data from our laboratory are discussed. PMID- 8452193 TI - Aversive reactions and alcohol use in Europeans. AB - Two hundred subjects of European descent completed a questionnaire about alcohol use and reactions to alcohol. Eleven subjects (5.5%) reported that they always experienced unpleasant reactions after small amounts of alcohol, and these subjects reported significantly lower levels for quantity and frequency of habitual alcohol use, and fewer drinks in the preceding 7 days, than the other subjects. Reactions to alcohol, either genetic or acquired, can therefore be significant in determining alcohol use in non-Asian groups. PMID- 8452194 TI - Anticipated stimulant and sedative effects of alcohol vary with dosage and limb of the blood alcohol curve. AB - Anticipations of alcohol's effects reportedly covary with the amount consumed. Alcohol's stimulant and sedative properties also may contribute to alcohol consumption. Anticipations of stimulant and sedative effects have not been investigated extensively. The present study examined the stimulant and sedative effects subjects anticipated experiencing if they were on the ascending or descending limb of the blood alcohol curve after consuming two or four standard drinks. One hundred sixty-six undergraduates reported anticipating greater stimulant effects than sedative effects on the ascending limb of the blood alcohol curve, and greater sedative effects than stimulant effects on the descending limb. Subjects also reported anticipating larger effects with larger doses. Men tended to anticipate smaller effects than women. These results support the notion that specific anticipated effects vary with dosage and the limb of blood alcohol curve, suggesting that the study of anticipated effects of alcohol should employ these variables. PMID- 8452195 TI - Development and validation of the Biphasic Alcohol Effects Scale. AB - Alcohol produces stimulant and sedative effects, and both types of effect are thought to influence drinking practices. This article describes the development and preliminary validation of the Biphasic Alcohol Effects Scale (BAES), a self report, unipolar adjective rating scale designed to measure both stimulant and sedative effects of alcohol. An initial pool of 12 stimulant and 12 sedative items was derived from previous alcohol effect measures, and from descriptors of intoxication generated by subjects during interviews conducted on both the ascending and descending limbs of the blood alcohol curve. This item pool was administered to a sample of sober college students twice, with a 2-week inter test interval. Items that were difficult to comprehend, or that had high ratings or low test-retest reliability, were eliminated, resulting in a seven-item stimulant subscale and a seven-item sedative subscale. These subscales showed high internal consistency in a sober state, which was not improved by additional item deletion. The data from this study also provided a basis for revising the instructions for the BAES. The new 14-item instrument was then given to 30 male and 12 female nonalcoholics on the ascending and descending limbs of the blood alcohol curve, after the administration of either 0.75 ml/kg alcohol (males) or 0.65 ml/kg alcohol (females). Internal consistency was high for both BAES subscales on both limbs of the blood alcohol curve (Cronbach's alpha = 0.85 to 0.94), and was not improved by additional item deletion. Factor analyses conducted on both limbs of the blood alcohol curve supported the proposed factor structure of the BAES.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452196 TI - Ethanol alters the metabolic response of isolated perfused rat liver to a phagocytic stimulus. AB - Intercellular communication in the liver is a potentially important mechanism for the regulation of hepatic metabolism. Since alcohol (ethanol, ETOH) can interact with both parenchymal and nonparenchymal cells, the present study was performed to assess the possible effects of ETOH on the nonparenchymal cell-to-hepatocyte signal traffic by studying the glycogenolytic and glycolytic response of the perfused rat liver to colloidal carbon, a phagocytic stimulus for Kupffer and sinusoidal endothelial cells. Livers from fed rats were perfused with hemoglobin free Krebs Ringer bicarbonate buffer containing ETOH (20 mM) or acetaldehyde (1 mM). Twenty minutes after initiating the infusion of ETOH or acetaldehyde, colloidal carbon was infused and the rate of carbon uptake, glucose, lactate and pyruvate output, and oxygen consumption were determined. In control livers, carbon stimulated the output of glucose (60%), lactate (25%), and pyruvate (53%), without affecting the lactate/pyruvate ratio. ETOH, but not acetaldehyde, enhanced the carbon effect on glucose output (38%), but suppressed the increased lactate and pyruvate output (48% and 91% respectively) resulting in a dramatic 10 fold increase in the lactate/pyruvate ratio. By using inhibitors of cyclooxygenase or alcohol dehydrogenase (indomethacin and 4-methylpyrazole, respectively) in the presence of carbon and/or ETOH, we determined that: (1) following carbon stimulation prostaglandins are the likely mediators secreted by nonparenchymal cells that increase carbohydrate output; and (2) the ETOH-induced enhancement of carbon-stimulated glycogenolysis is also mediated by prostaglandins and is not dependent on the oxidative metabolism of ETOH. PMID- 8452197 TI - Does psychomotor sensitivity to alcohol predict subsequent alcohol use? AB - Data from 42 male and 58 female subjects who participated in the Colorado Alcohol Research on Twins and Adoptees (CARTA) project were subjected to model-fitting analyses. The aim of the present study was to use linear structural equation models to determine whether differences in previously measured psychomotor sensitivity to alcohol predict differences in self-reported alcohol consumption over a 4-year period. LISREL model-fitting results indicate that, for male subjects, only rail walking insensitivity is predictive of alcohol use reported 2 years after their initial CARTA testing. For females, only hand steadiness sensitivity is predictive of alcohol use reported 2 years after their initial CARTA testing. The results for males support a hypothesis that would consider alcohol insensitive individuals at greater risk for alcohol abuse. The female results, however, would argue against such a hypothesis. With only one measure of sensitivity predicting alcohol use at only one out of four time points, in both men and women, the overall results suggest that our three measures of psychomotor sensitivity to alcohol are, in general, poor predictors of alcohol consumption in this sample. PMID- 8452198 TI - The role of antisocial, affective, and childhood behavioral characteristics in alcoholics' neuropsychological performance. AB - Chronic alcoholics demonstrate cognitive deficits when compared with nonalcoholics. These deficits are typically attributed to the direct effects of ethanol and its metabolites on the central nervous system (CNS). There are other factors, however, that differentiate alcoholics from controls, such as personality or behavioral characteristics. These factors may affect neuropsychological performance and thus alter the interpretation of alcoholic cognitive deficits as resulting solely from alcohol's toxic effects. To investigate this question, male and female alcoholics and peer nonalcoholic controls were compared on personality, behavioral, and cognitive measures. Alcoholics had greater numbers of antisocial behaviors, childhood behavioral disorder symptoms (CBD), and affective symptomatology, and had poorer neuropsychological performance than controls. The three personality and behavioral factors were positively intercorrelated with each other, and were negatively related to cognitive performance. The CBD factor proved to be the most consistent predictor of neuropsychological performance for both alcoholics and controls, and males and females. While the behavioral factors differentiated alcoholics from controls and predicted performance, significant differences between the groups in cognitive performance still remained when these factors were taken into account. PMID- 8452199 TI - Increased metabolism of acetaminophen in chronically alcoholic patients. AB - The aim of this work was to determine whether the metabolism of acetaminophen increases in chronic alcoholics, and consequently whether the production of its hepatotoxic metabolite is enhanced. For this purpose, the pharmacokinetics of acetaminophen were compared in 12 alcoholic men and 12 healthy controls. After a 12-hr fast, the patients (on the 3rd hospital day) and volunteers were given 1 g of oral acetaminophen at 8.00 AM. Venous blood samples were drawn before drug intake and at regular intervals after to evaluate plasma acetaminophen concentrations. The elimination half-life of acetaminophen was significantly shorter in the alcoholic patients than in the controls (1.70 +/- 0.55 vs. 2.84 +/ 0.30 hr, p < 0.001). Similarly, total plasma acetaminophen clearance was significantly higher in the patients than in the controls (29.19 +/- 13.37 vs. 24.45 +/- 11.10 l/hr, p < 0.05). These results confirm that the metabolism of acetaminophen increases in chronic alcoholism and consequently suggest that its potential liver toxicity might be enhanced. PMID- 8452200 TI - Teratogenic effects of alcohol on infant development. AB - Results of previous studies of effects of drinking during pregnancy on standardized tests of infant development have varied, depending on level of exposure. This study of 382 Black, inner city infants confirmed effects of moderate-to-heavy prenatal alcohol exposure on Bayley Scale performance originally observed in a White, middle class cohort. Effects of second and third trimester drinking were as strong or stronger than those of drinking at the time of conception. New methods for reducing the Bayley Scale data suggested specific deficits relating to emergence of the ability to imitate modeled behavior and the development of standing and walking. The incidence of very poor performance (bottom 10th percentile) on the Bayley Mental Development Index more than doubled in children whose mothers averaged at least 0.5 oz absolute alcohol per day during pregnancy, indicating that this exposure has a clinically meaningful impact at markedly lower levels than those associated with full fetal alcohol syndrome. Clinically meaningful effects on the Psychomotor Development Index, by contrast, were seen only in the infants of heavy drinking mothers with overt symptomatology of alcohol abuse. Adverse effects on Bayley Scale performance were more prevalent in the infants of women more than 30 years of age. PMID- 8452201 TI - Detection of alcoholism in schizophrenia using the MAST. AB - The classification accuracy of the Michigan Alcoholism Screening Test (MAST) for detecting alcoholism in a community sample of 75 schizophrenic outpatients was assessed, as a replication and extension of Searles et al. (1990). The criterion diagnosis of alcohol use disorder was based on the convergence of ratings from multiple sources. The MAST classified 85% of the sample correctly, and item-based analyses showed that various subsets were equally effective, indicating a high degree of redundancy among MAST items. Differences between our sample and that of Searles et al. influenced the choice of MAST items for optimal detection and classification, and males were consistently classified more correctly than females. These results suggest that the construction of a brief and accurate detection instrument for alcohol use among schizophrenic patients may be possible, although attention to subpopulation differences will be required. PMID- 8452202 TI - Alcohol use and periodic limb movements of sleep. AB - Alcohol causes significant sleep disturbance but the causes are not well understood. We investigated the relationship between alcohol use and periodic limb movements in a large population of patients at a sleep disorders center. The likelihood of having a clinically significant number of periodic leg movements (more than 20 per hour of sleep) was increased 3-fold in women who consumed two or more alcoholic drinks per day compared with those who did not (25% versus 8%). A similar relation was found among men (22% versus 13%). In addition, women who consumed two or more drinks per day were more likely to report symptoms of restless legs and to be diagnosed with restless legs syndrome. These findings suggest that periodic leg movements contribute to sleep disturbance in a significant proportion of alcohol users. Alcohol use may increase the frequency of periodic leg movements in susceptible individuals. On the other hand, subjects with symptoms related to periodic leg movements may be using alcohol to relieve symptoms, or the movements may be secondary to alcohol-induced sleep disturbance. PMID- 8452203 TI - Amethystic agents and adjunct behavioral therapy and psychotherapy. PMID- 8452205 TI - Molecular mechanism of ethanol metabolism by human brain to fatty acid ethyl esters. AB - Ethanol metabolism in the human brain has been documented to occur with the formation of fatty acid ethyl esters. These neutral lipids can disorder membranes and interrupt mitochondrial function. Their formation is under the control of three synthases, localized to grey matter and purified to homogeneity. cDNA cloning demonstrates two of these enzymes to be GSH S-transferases and has enabled initiation of genetic studies of alcohol-induced CNS injury. PMID- 8452204 TI - Brain lesions in alcoholics. AB - Brain lesions in alcoholics are multifactorial in origin. Ethanol neurotoxicity, Wernicke's encephalopathy, hepatocerebral degeneration, head trauma, central pontine myelinolysis, Marchiafava-Bignami syndrome, pellagra, and premorbid pathological conditions, such as fetal alcohol syndrome, may all contribute to cognitive dysfunction in alcoholics. With the exception of ethanol neurotoxicity, all of these conditions are associated with specific neuropathological lesions. Wernicke's encephalopathy, the neurological syndrome of thiamine deficiency, is frequently overlooked during life and may cause global dementia as well as the more familiar Korsakoff's amnestic syndrome. Distinguishing ethanol neurotoxicity from nutritional deficiency can be facilitated by magnetic resonance imaging, which can visualize some of the specific macroscopic lesions of Wernicke's encephalopathy, central pontine myelinolysis, cerebellar degeneration, and Marchiafava-Bignami syndrome. Computerized morphometric studies of alcoholic brains have revealed ventricular enlargement, selective loss of subcortical white matter, and alterations in neuronal size, number, architecture, and synaptic complexity. These lesions tend to be more severe when there is coexisting nutritional deficiency or liver disease, suggesting that ethanol neurotoxicity may not be the sole cause. A search for similar lesions in nonalcoholic Wernicke's encephalopathy and nonalcoholic liver disease will help determine the specificity of these lesions. PMID- 8452206 TI - Genetic sensitivity to thiamine deficiency and development of alcoholic organic brain disease. PMID- 8452207 TI - The relationship of outlet densities to alcohol consumption: a time series cross sectional analysis. AB - The implementation of regulations on access to alcoholic beverages, whether through beverage taxes or restrictions on the availability of this commodity through alcohol outlets, has often been proposed as a legitimate and politically feasible approach to the prevention of alcohol-related problems. Empirical studies of the effects of these approaches to regulation on alcohol consumption and problems, however, have not been unanimous in their support of these preventive measures. While support exists for the suggestion that increases in alcohol beverage prices reduce consumption and have preventive effects upon the occurrence of problems, relatively little evidence exists for the supposition that the regulation of alcohol availability will have similar preventive effects. The lack of evidence in support of the latter thesis rests primarily upon the difficulty of obtaining sufficient data to examine comprehensive models of access to alcohol. The current paper analyzes aggregate time series cross-sectional data from states of the U.S. to evaluate the relationships between alcohol beverage prices, availability, and alcohol sales within one analytic model. The model relates beverage prices and alcohol availability directly to alcohol sales in the context of an assumed simultaneous relationship between sales and availability. The results show that, independent of the effects of beverage prices, and controlling for the endogeneity of sales and availability, physical availability of alcohol was directly related to sales of spirits and wine. PMID- 8452208 TI - Determinants of ethanol and acetaldehyde metabolism in chronic alcoholics. AB - We have studied the factors determining the rate of ethanol and acetaldehyde metabolism in a group of 25 alcoholics with varying degrees of liver lesion (from normal liver to cirrhosis) and in six nonalcoholic cirrhotics. In alcoholics the ethanol metabolic rate was related to hepatic function, estimated either by the aminopyrine breath test (r = 0.70, p < 0.001) or the indocyanine green clearance (r = 0.76, p < 0.01), and was independent of the activity of hepatic alcohol dehydrogenase and hepatic blood flow. In nonalcoholic cirrhotics blood acetaldehyde was always below the detection limit (0.5 microM), but elevated levels were found in 14 out of the 25 alcoholics. Alcoholics with elevated blood acetaldehyde showed a significantly higher ethanol metabolic rate than alcoholics with undetectable acetaldehyde (120 +/- 17 mg/kg/hr vs 104 +/- 11 mg/kg/hr, p < 0.02), but no differences were observed in the activities of alcohol and aldehyde dehydrogenases. Peak blood acetaldehyde levels were directly related to the ethanol metabolic rate (r = 0.48, p < 0.02), but not to activities of hepatic alcohol or aldehyde dehydrogenases. These results indicate that in chronic alcoholics the main determinant of the ethanol metabolic rate is hepatic function, while the rise of blood acetaldehyde is mainly dependent on the ethanol metabolic rate. Alcohol and aldehyde dehydrogenase activities do not seem to be rate-limiting factors in the oxidation of ethanol or acetaldehyde. PMID- 8452209 TI - Effects of ethanol concentration and fixed-ratio requirement on ethanol self administration by P rats in a continuous access situation. AB - Rats, from the alcohol preferring (P) line, were placed in operant chambers in which food pellets, water, and 10% ethanol (v/v) were available continuously for 23 hr/day. During Experiment 1, the effects of changing ethanol concentration and response requirement for ethanol were examined. Ten percent and 20% ethanol (v/v) were available on two fixed ratio (FR) schedules, FR 1 and FR 4, for 2 weeks each. During Experiment 2, the effects of increasing the response requirement for ethanol were investigated. Starting with FR 4, the FR requirement for ethanol doubled during 2-week intervals until FR 32 was in effect. For the final phase of these studies, water was placed in the dipper for 1 week followed by a return to 10% ethanol in the dipper. The results from Experiment 1 indicated that when the FR requirement was decreased from FR 4 to FR 1, ethanol-reinforced responding decreased but total daily intake increased. Lowering the FR requirement did not affect the number of ethanol bouts per day but bout size increased. Ethanol concentration had no effect on bout size but the number of bouts per day decreased when the concentration was increased to 20%. Since bout size was unchanged by increasing the ethanol concentration, intake per bout increased at 20% ethanol. The results from Experiment 2 indicated that increasing the response requirement for ethanol decreases ethanol intake. When water was placed in the dipper, responding decreased to the lowest levels observed in the experiment. When ethanol was returned to the dipper, responding returned to baseline levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452210 TI - Reaction of acetaldehyde with proteins: formation of stable fluorescent adducts. AB - The properties of stable acetaldehyde-protein adducts, using bovine serum albumin as a model protein, were investigated. Upon prolonged incubation at 37 degrees C and pH 7.4, the reaction of acetaldehyde and albumin yielded stable adducts that exhibited fluorescent properties. Reaction mixtures of acetaldehyde with polylysine or ethylamine also formed fluorescent products with similar fluorescent spectral properties like acetaldehyde-albumin adducts, indicating that the amino groups of protein alone can generate fluorescent products on reaction with acetaldehyde. When reactions of acetaldehyde with albumin or polylysine were conducted at 22 degrees C, stable binding reached a maximum after 24 hr of incubation and essentially remained at this level during the remaining 216 hr of incubation, and minimal-to-no fluorescence was associated with this binding. At 37 degrees C, stable binding was greater and increased continuously over the entire 216 hr of incubation. After an initial lag period of 24 to 48 hr, increases in fluorescence intensity paralleled the increases in stable binding. The presence of sodium cyanoborohydride, which reduces Schiff bases, in the reaction mixtures prevented fluorescence, indicating that Schiff bases are intermediates in the formation of fluorescent products. Both stable binding and fluorescence intensities were minimally affected by exhaustive dialysis (up to 144 hr), indicating that the fluorescent products were quite stable. These results suggest that an initial reaction of a Schiff base with another acetaldehyde molecule via an aldol condensation reaction gives rise to the formation of a crotonaldehyde Schiff base derivative. This reactive intermediate could then undergo further condensation reactions and form advanced conjugated products, some of which could be fluorescent. PMID- 8452211 TI - Ethanol ingestion increases susceptibility of mice to Listeria monocytogenes. AB - Excessive consumption of alcohol is associated with an increase in the frequency and severity of infectious diseases. Ethanol adversely affects specific and nonspecific aspects of the immune response. We used a murine model to determine whether ethanol ingestion impairs host mechanisms of resistance to Listeria monocytogenes. Naive mice and mice immune to L. monocytogenes were pair-fed either a Leiber-DeCarli liquid diet containing 7% (v/v) ethanol or an isocaloric control diet for 7 days. Then, nonimmune mice were given a sublethal dose of L. monocytogenes and studied 2 and 5 days after infection, and immune mice were challenged with a lethal dose of L. monocytogenes and studied 5 days after infection. Multifocal liver abscesses developed in nonimmune ethanol-treated and control mice 2 days after infection. Bacterial colony counts in the spleens were similar between the two groups; however, counts in the livers were slightly higher in ethanol-treated mice as compared with those in control mice. Five days after infection the nonimmune ethanol-treated mice had large necrotizing liver granulomas and organ bacterial colony counts 100 to 1000 times higher than those in control mice. Immune ethanol-treated mice had large areas of liver necrosis and inflammation containing numerous Gram-positive bacilli, whereas immune control mice had small, well-formed granulomas and much less necrosis. Organ bacterial colony counts were about 100 times higher in immune ethanol-treated mice as compared with those in immune control mice. Liver enzyme levels and mortality were significantly higher in ethanol-treated immune and nonimmune mice as compared with those in immune and nonimmune control mice. Data support the suggestion that ethanol consumption impairs the development and expression of T cell-mediated immunity of mice to L. monocytogenes, resulting in increased susceptibility to infection with this organism. PMID- 8452212 TI - Repeated episodes of ethanol withdrawal potentiate the severity of subsequent withdrawal seizures: an animal model of alcohol withdrawal "kindling". AB - Prior experience with ethanol (EtOH) withdrawal may sensitize an individual to subsequent withdrawal episodes. It has been hypothesized that the progressive intensification of the EtOH withdrawal syndrome following repeated episodes of EtOH intoxication and withdrawal may represent the manifestations of a "kindling" mechanism. The purpose of this study was to develop an animal model of EtOH withdrawal that is sensitive to the effects of prior withdrawal experience. Adult male C3H mice were chronically exposed to EtOH vapor in inhalation chambers prior to withdrawal testing. A multiple withdrawal (MW) group received 3 cycles of 16 hr EtOH vapor separated by 8-hr periods of abstinence; a single withdrawal (SW) group received a single bout of EtOH exposure (16 hr); a third group (SW-CONT) experienced a single withdrawal episode after receiving the equivalent amount of EtOH intoxication as the MW group (16 x 3 = 48 hr), but in a continuous (uninterrupted) fashion; and a fourth group (C) served as controls, not receiving any EtOH exposure throughout the study. Severity of the withdrawal response was assessed by scoring handling-induced convulsions hourly for the first 10 hr and then at 24 hr postwithdrawal. The results indicated that the severity of EtOH withdrawal seizures was significantly greater in animals that had a prior history of withdrawal episodes (MW group) in comparison to a separate group of animals that were tested following a single withdrawal from the same 16-hr intoxication period (SW group).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452213 TI - Comparison of in vitro transcriptions using various types of DNA templates. AB - Improvements in the synthesis of RNA using T7 RNA polymerase and synthetic deoxyoligonucleotides containing the T7 RNA promoter are described. Yields were highest when the double-stranded promoter was generated from a hairpin hybridized to the single-stranded DNA template or when the templates were assembled by ligation of shorter chemically synthesized deoxyoligonucleotides. Our results show that for the synthesis of RNA, templates prepared by ligating smaller deoxyoligonucleotides were as much as 25 times more efficient than those prepared by one-step chemical synthesis. PMID- 8452214 TI - The use of streptavidin-coated magnetic beads and biotinylated antibodies to investigate induction and repair of DNA damage: analysis of repair patches in specific sequences of uv-irradiated human fibroblasts. AB - A new immunoextraction method using biotinylated antibodies and streptavidin coated magnetic beads has been developed and applied to study the repair of uv induced DNA damage in specific DNA sequences. uv-irradiated cells were allowed to carry out DNA repair for various time intervals in the presence of 5 bromodeoxyuridine (BrdU). Purified and restricted DNA was subjected to an immunoextraction method employing an anti-BrdU antibody (alpha Brdu), biotinylated goat antimouse antibodies (G alpha Mbio), and streptavidin-coated polymeric magnetic beads. Separation of BrdU containing DNA was achieved by using a magnetic device. This extraction procedure resulted in two fractions of DNA, i.e., BrdU-containing and non-BrdU-containing DNA. Both fractions were blotted on filters and subsequently hybridized with specific DNA probes to determine the relative amount of defined fragments in the two fractions of DNA. Repair experiments using normal primary human fibroblasts showed no difference in the incorporation of repair label in the active adenosine deaminase gene and the inactive 754 locus during the first 4 h following uv irradiation. After longer repair times the active gene incorporated more repair label than the inactive gene, consistent with the known preferential repair of cyclobutane pyrimidine dimers from active housekeeping genes. PMID- 8452215 TI - Analysis of the neurotoxin beta-ODAP and its alpha-isomer by precolumn derivatization with phenylisothiocyanate. AB - A method is presented for determining 3-N-oxalyl-2,3-diaminopropanoic acid (beta ODAP), the most potent neurotoxic substance of the seeds and seedlings of Lathyrus sativus, and its much less toxic 2-isomer (alpha-ODAP). The separation of the two forms is achieved after derivatization with phenylisothiocyanate employing a HPLC system. This method was used to monitor the isomerization of beta-ODAP to alpha-ODAP at different time intervals and to quantify the toxin level in seed extracts. PMID- 8452216 TI - Determination of detergent critical micellar concentration by solubilization of a colored dye. AB - The critical micellar concentration of detergent was determined by the solubilization of a colored dye found in standard waterproof pen. The amount of solubilized dye is directly proportional to the concentration of micelles in the detergent solution. The method has been validated with a series of standard detergents. PMID- 8452217 TI - Respiration measurements in small scale. AB - The design and operation of a small (< 40 microliters) reaction vessel with membrane-covered oxygen electrode is described. The equipment's productivity and experimental versatility is similar to that of equipment using 100 times more biological material. Control experiments showed that respiration experiments are made with virtually no systematic errors and random errors of less than 2%. PMID- 8452218 TI - Zymogram of proteases made with developed film from nondenaturing polyacrylamide gels after electrophoresis. AB - A simple, extremely versatile method for preparing zymograms from proteases after nondenaturing Phast-System gel electrophoresis is described. After completion of the run and before staining, an electropherogram and a piece of developed, single side coated X-ray film are brought into contact for 5 min at room temperature. The film overlay is then separated and the gel is stained for protein. The zymogram on the X-ray film is generated by simply pouring about 10 ml of a suitable buffer solution at 30 to 50 degrees C over the film strip. Clearing zones appeared within a few seconds to a few minutes depending on protease amount. For the alkaline protease subtilisin BL the lower limit of detectability was 10 ng applied to the gel prior to electrophoresis. For preservation and archiving the zymogram film is simply rinsed with distilled water and air-dried. The film can be cut to size and mounted for a slide projector, or the film can serve as a negative for photographic enlargements. The clearing zone area is proportional to the amount of protease from 10 to 100 ng of protein. PMID- 8452219 TI - A high-performance liquid chromatography assay for threonine/serine dehydratase. AB - Threonine dehydratase, a key enzyme leading to the biosynthesis of isoleucine, catalyzes the production of 2-ketobutyrate from threonine. An uv/fluorometric HPLC assay for threonine dehydratase has been developed that involves derivatization of the 2-ketoacids produced by the enzyme using a specific derivatizing agent, o-phenylenediamine. The derivatized ketoacids can be detected spectrophotometrically or fluorometrically. This novel assay is over 1000-fold more sensitive than the commonly used dinitrophenyl hydrazine derivatization assay. In addition, the HPLC assay allows the identification of the reaction product(s), and can be used to examine the reaction using mixtures of the two substrates, threonine and serine. PMID- 8452220 TI - cDNA equalization for reverse transcription-polymerase chain reaction quantitation. AB - Reverse transcription coupled with the polymerase chain reaction has been increasingly utilized to study gene expression. However, most previously published quantitative techniques are limited by accurate initial RNA quantitation and do not account well for the relative efficiency of reverse transcription. We have developed a technique of labeling and quantitating the random-primed cDNA product of a reverse transcription reaction. Using the polymerase chain reaction in conjunction with template dilutions or with an internal competitive template, we show that by normalizing the cDNA input into the polymerase chain reaction, we get accurate quantitation of gene expression. We call this procedure cDNA equalization of reverse transcriptase-polymerase chain reaction. This method is ideal for small clinical samples where accurate quantitation of input RNA is difficult. PMID- 8452221 TI - Purification of interferon gamma-interferon gamma receptor complexes by preparative electrophoresis on native gels. AB - Cytokine-receptor complexes are required for certain studies including crystallization, NMR spectra, and investigation of the biological response mechanism to the cytokine. The purity of the ligand-receptor complex is critical for most of these applications. We investigated the possibility of purifying protein-protein complexes by electrophoresis on native gels. Starting with partially purified mouse and highly purified human proteins, we prepared milligram amounts of interferon gamma-interferon gamma receptor complexes by preparative electrophoresis on nondenaturing polyacrylamide gels. In both cases, pure ligand-receptor complexes with the correct stoichiometry of binding were recovered. Electrophoresis on preparative native gels may prove to be of general interest for the preparation of protein-protein complexes to be used in diverse studies. PMID- 8452222 TI - Identification of covalent adducts to protein sulfur nucleophiles by alkaline permethylation. AB - We recently reported on the identification of metabolites of the hepatotoxin bromobenzene covalently bound to rat liver protein sulfur nucleophiles (D. E. Slaughter and R. P. Hanzlik, Chem. Res. Toxicol. 4, 349-359 (1991). Central to that study was our development of a method called alkaline permethylation which converts protein-S adducts of xenobiotic electrophiles to stable extractable thioanisole derivatives. We report here on substantial improvements to our original alkaline permethylation method which should greatly expand its potential utility. Specifically, we have developed significantly milder reaction conditions, eliminated side reactions, improved the amount of and consistency of thioanisole yields from various mercapturic acid model compounds, and increased the overall sensitivity of the method at least 50-fold. Using the procedure described herein it is routinely possible to generate, detect, and identify by GC/MS as little as 2 pmol of a thioanisole derivative. This method is potentially quite general and should prove useful for studies in the toxicology of reactive metabolites, for industrial hygiene and biomonitoring, and for agrichemical residue analysis. PMID- 8452223 TI - Enzymatic assay for L-serine and glyoxylate involving the enzymes in the serine pathway of a methylotroph. AB - An easy, rapid, and accurate enzymatic assay method for L-serine was established involving two enzymes, serine-glyoxylate aminotransferase (SGAT, EC 2.6.1.45) and hydroxypyruvate reductase (HPR, EC 1.1.1.81), in the serine pathway of the methylotrophic bacterium, Hyphomicrobium methylovorum (IFO 14180), from which they were purified. This method consists of two reaction steps: the first is the nearly irreversible transamination of L-serine and glyoxylate by SGAT, and the second is the HPR reaction involving NADH, which comprises the absolutely irreversible reduction of hydroxypyruvate derived from L-serine by SGAT. The amounts of L-serine were determined spectrophotometrically as the decrease in the amount of NADH. When the values determined with the present enzymatic method were compared with those obtained with an amino acid analyzer, the correlation coefficient was found to be 0.9963. This method can also be applied to the assaying of glyoxylate. PMID- 8452224 TI - Bioluminescent immunoassay with a protein A-luciferase fusion protein. AB - Protein A and firefly luciferase were genetically fused and the resulting fusion protein was applied to a bioluminescent immunoassay. The gene fusion plasmid, pMALU2, was constructed by inserting the structural gene of luciferase into a protein A expression vector, and was expressed in Escherichia coli. The resulting fusion protein of molecular weight 91 kDa retained not only the enzymatic activity of luciferase but also the binding capability of protein A to the Fc region of immunoglobulin G (IgG). The bioluminescent immunoassay was performed with the fusion protein and human IgG was determined in the concentration range from 10(-3) to 10(-7) g/ml. PMID- 8452225 TI - Sedimentation equilibrium of detergent-solubilized membrane proteins in the preparative ultracentrifuge. AB - Working with detergent-solubilized bacteriorhodopsin we have used a table top preparative centrifuge for determination of M(r) of membrane proteins by sedimentation equilibrium. We demonstrate the use of two new methods to measure protein concentration as a function of distance from rotor axis: (i) peak integration after HPLC on silica gel, and (ii) microdensitometry after sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Coomassie blue staining. These methods, although somewhat lengthier than conventional spectrophotometric methods, are more reliable, especially in the presence of a large amount of detergent and small amount of protein. In addition they provide independent information on the status of the protein after sedimentation equilibrium, the association of the solubilized units being readily detected by gel chromatography and proteolytic cleavage by SDS-PAGE. PMID- 8452226 TI - Quantification of diacylglycerols by capillary gas chromatography-negative ion chemical ionization-mass spectrometry. AB - We describe a method for quantifying diacylglycerols as their 1 pentafluorobenzoyl-2-acyl-3-acetyl-glycerol derivatives by capillary gas chromatography-negative ion chemical ionization-mass spectrometry. The basis of the method resides in the sequential treatment of diacylglycerols with acetic anhydride, pancreatic lipase, and pentafluorobenzoyl chloride. Cultured rat mesenteric artery vascular smooth muscle cells (VSMC) were incubated for 20 min in the presence of vehicle or vasopressin (10(-7) M). The incubations were stopped by aspirating the medium and adding 2 ml of methanol containing 790 pmol of internal standard 1-stearoyl-2-(10,13)-nonadecadienoyl- glycerol. After extraction, diacylglycerols were isolated by thin-layer chromatography, acetylated, and treated with pancreatic lipase. The resulting 2-acyl-3 acetylglycerols were then purified by thin-layer chromatography, transformed into their 1-pentafluorobenzoyl-derivatives, and monitored by capillary gas chromatography-negative ion chemical ionization-mass spectrometry on the selected ion-monitoring mode (m/z 614 and 604 for 2-arachidonoyl and 2-nonadecadienoyl species, respectively). The levels of diacylglycerols bearing an arachidonoyl moiety were 128 +/- 26 pmol/100 nmol lipid phosphorus in resting cells and 333 +/ 28 in stimulated cells (mean +/- SD, n = 3, P < 0.01). The presence of diacylglycerol species bearing an oleoyl or a linoleoyl group at the second position could also be detected in VSMC preparations by this approach. This new method can be applied to quantitate various diacylglycerol species bearing distinct acyl moieties at the second position of the glycerol molecule. PMID- 8452227 TI - Interactions of IgG with specific erythrocyte membrane proteins in affinity electrophoresis are highly dependent on low ionic strength conditions. AB - Agarose gel affinity electrophoresis has been used to demonstrate interactions between autologous IgG and specific erythrocyte membrane proteins. These binding phenomena are here further examined by combining affinity electrophoresis with affinity chromatography, absorption experiments, and immunoblotting. It is demonstrated that the interactions are highly dependent on polyreactive IgG binding favored by the low ionic strength conditions of the electrophoretic assay. Thus, about 25% of normal IgG under low ionic strength conditions bound to the purified cytoskeletal protein, spectrin, immobilized on Sepharose. This IgG reacted in affinity electrophoresis in a polyspecific fashion with the same array of membrane proteins as before the low ionic strength-affinity chromatography. Further, the binding seen in affinity electrophoresis, including the interaction with spectrin, was completely abolished by preabsorption of the IgG with spectrin devoid membranes. The charge characteristics of an IgG subclass might be responsible for the observed binding. However, the observed precipitate formation suggested an interaction involving at least two binding sites on each molecule and the binding appears to require structurally intact IgG because reductive treatment with dithiothreitol diminished the reactivity considerably. Conclusively, under the conditions of affinity electrophoresis with ligand present in the gel, electrostatic interactions are amplified. The degree of binding of IgG to erythrocyte membrane proteins that take place under these conditions does not reflect binding which would occur to the same extent under physiological ionic strength conditions. PMID- 8452228 TI - A subtractive hybridization method to isolate tissue-specific transcripts: application to the selection of new brain-specific products. AB - A method based on subtractive hybridization of brain complementary DNAs with peripheral messenger RNAs has enabled us to construct an enriched brain-specific cDNA library. Single-stranded cDNAs (ssc DNAs) were synthesized from brain polyadenylated mRNAs and subsequently hybridized with peripheral mRNAs immobilized on nitrocellulose membrane. Unhybridized sscDNAs were converted into double-stranded cDNAs and cloned into plasmid pUC13. The screening of the resulting library showed that a high percentage of the cloned cDNAs corresponded to mRNAs specifically transcribed in the brain. PMID- 8452229 TI - A colorimetric assay for amino nitrogen in small volumes of blood: reaction with beta-naphthoquinone sulfonate. AB - An assay has been developed for the colorimetric estimation of total amino acids in small volumes (100 microliters) of whole blood. The procedure utilizes the reaction of amino nitrogen with beta-naphthoquinone sulfonate. It represents a substantial improvement on previously published methods by decreasing reagent volumes and accurately specifying and maintaining pH conditions for the reaction itself (9.2-9.4) and for removal of excess reagent prior to measurement of the resulting complex (2.2-2.4). Ammonia is the only compound shown to significantly interfere with the assay but this is not a problem at physiological concentrations. PMID- 8452230 TI - Tannin-mediated attachment of avidin provides complement-resistant immunoerythrocytes that can be lysed in the presence of activator of complement. AB - It was shown previously that avidin attachment to biotinylated erythrocytes induces their lysis by homologous complement via the alternative pathway. This phenomenon hinders the use of avidin-coated immunoerythrocytes as carriers for drug targeting. In the present work we demonstrated that attachment of avidin to erythrocytes via the cross-linking agent tannin does not induce their lysis by complement. Tannization allows attachment of about 5 x 10(5) molecules of avidin per erythrocyte, which is comparable to the value obtained after treatment with biotin esters. In contrast to biotinylated avidin-coated erythrocytes, tannized avidin-coated erythrocytes were not lysed by complement. Tannization itself does not reduce the erythrocyte sensitivity to lysis by complement in the presence of activators of the complement (hemolytic antibody or activators of the alternative pathway). Therefore, the avidin-induced lysis by complement depends on the mode of avidin attachment to erythrocyte. Complement-resistant tannized erythrocytes coated with avidin bind biotinylated immunoglobulins (to 7 x 10(4) molecules per cell), suggesting that tannization might be used for the preparation of complement-resistant immunoerythrocytes. PMID- 8452231 TI - A method to estimate the ratio of absorption coefficients of two wavelengths using phase-modulated near infrared light spectroscopy. AB - Near infrared spectroscopy is a very useful tool for monitoring the oxygen saturation of living tissue noninvasively. We can calculate the hemoglobin oxygen saturation within tissue, using the ratio of the absorption coefficients (mua) at two different wave lengths of light. Biological tissue has a very high effective scattering factor (mu's), which elongates an optical path length and makes it difficult to compute the mua by the conventional method using continuous light. Phase-modulated spectroscopy (PMS) measures the path length which is a complex function of the mua and mu's. To obtain the ratio for mua, we have to eliminate the effects of the mu's from the obtained value by the PMS method. In this report, we present a theory and an experimental result which show that the inverse of the squared ratio of two phase angle differences at two different separations obtained by two different light wavelengths provides a good estimate of the ratio at these wavelengths. PMID- 8452232 TI - Maximal expression of recombinant cDNAs in COS cells for use in expression cloning. AB - In the process of establishing an expression cloning system for cell surface receptors we examined parameters which influence the expression of foreign genes in COS cells. The bacterial beta-galactosidase gene was chosen as a reporter gene, since it permits the determination of (i) the fraction of cells transfected as well as (ii) the total activity of the synthesized enzyme in parallel experiments. This renders it possible to calculate the enzyme activity per individual cell. In transfected COS cells, the plasmid pXMgal directed a 20- and 10-fold higher beta-galactosidase activity than pCH110 and pCDLgal, respectively. DEAE-dextran-mediated DNA uptake and protoplast fusion were found to result in higher expression rates than lipofection and electroporation. A coincubation of the cells with chloroquine during the DEAE-dextran transfection protocol caused, as reported, an increase of beta-galactosidase positive cells but considerably reduced the total beta-galactosidase activity. However, a 10% DMSO shock at the end of the transfection procedure simultaneously increased the number of transfected cells and the total beta-galactosidase activity, thus maintaining the high expression per single cell. Using these optimized conditions, COS-1 cells expressed higher amounts of recombinant protein than COS-7 cells. PMID- 8452233 TI - Determination and derivatization of protein thiols by n-octyldithionitrobenzoic acid. AB - n-Octyl-5-dithio-2-nitrobenzoic acid (ODNB), the reaction product of n-octane-1 thiol and Ellman's reagent, can be isolated in crystalline form. Like Ellman's reagent, ODNB can be used for the titration of SH groups in proteins, but with considerable advantages: Due to the absence of one negative charge and the presence of a lipophilic hydrocarbon chain, titrations of protein thiols are significantly faster. Normally, endpoints are reached after 5-30 min, while the corresponding reaction with Ellman's reagent may take 1-2 h. Another advantage of ODNB is that it finds access to thiol groups which normally remain undetected. With myosin S1, for example, ODNB reacts with a thiol group which is not reactive with Ellman's reagent. Although ODNB has detergent properties, reaction of this thiol group as a consequence of denaturation seems unlikely, because ODNB was used below its critical micelle concentration and all other thiols of myosin S1 remained buried. The n-octylthiol derivatives of proteins formed by reaction with ODNB can be used for transient protection of thiols, for example, during purification procedures, or for a reversible blocking of SH groups involved in biochemical reactions. PMID- 8452234 TI - N,N-(2,4-dinitrophenyl)octylamine derivatives for the isolation, purification, and mass spectrometric characterization of oligosaccharides. AB - A simple, sensitive method for the structural characterization of oligosaccharides by fast atom bombardment-mass spectrometry (FAB-MS) has been designed. Oligosaccharides are labeled with a uv chromophore (which also serves as a charge stabilizing group) and with a hydrophobic alkyl tail. The chromophore, a 2,4-dinitrophenyl group, aids uv detection during HPLC and stabilizes negative ion species formed during analysis by FAB-MS. The hydrophobic tail, provided by an octyl group, enhances the surface activity of the analytes and makes them amenable to separation by reverse-phase chromatography using a C18 bonded phase. This method was applied to the structural analysis of the components of a mixture of starch maltodextrins with a degree of polymerization 1 16, to the analysis of the structure of pure maltohexaose, and to a previously characterized oligosaccharide from a Rhizobium capsular polysaccharide. The method gave a good yield of [M-H]- anions for the derivatized compounds, which in most cases were detectable at a level of about 1 pmol. In the case of maltohexaose, four series of sequence anions corresponding to sequential loss of glycosyl residues from the reducing and nonreducing end by different mechanisms were observed. The mixture of derivatized malto-oligosaccharides could easily be separated by HPLC. Based on the relative proportions of the individual oligomers in the mixture calculated from HPLC analysis, even though the higher oligomers were present in amounts of about 0.1%, they could still be easily detected in mass spectra of the entire mixture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452235 TI - A fluorometric assay for glycosylasparaginase activity and detection of aspartylglycosaminuria. AB - Recent experimental work on the mechanism of action of glycosylasparaginase suggests that the enzyme specifically reacts toward the L-asparagine or L aspartic acid moiety of its substrates. Based on this, a new sensitive assay for glycosylasparaginase activity has been developed using L-aspartic acid beta-(7 amido-4-methylcoumarin) as substrate. Release of 7-amino-4-methylcoumarin was determined fluorometrically. At pH 7.5, Km = 93 microM, and as little as 1 ng of glycosylasparaginase could be detected with the assay. Hydrolysis of the substrate was inhibited by diazo-oxonorvaline, a specific inhibitor of glycosylasparaginase. In biological samples, the fluorometric assay is 40-100 times more sensitive than other published methods for glycosylasparaginase. This new assay enables a rapid enzymatic diagnosis of aspartylglycosaminuria--a genetic deficiency of glycosylasparaginase activity--with leukocyte and fibroblast samples. PMID- 8452236 TI - Purification of cysteine-rich bioactive peptides from leukocytes by continuous acid-urea-polyacrylamide gel electrophoresis. AB - A new continuous acid-urea-polyacrylamide gel electrophoresis (CAU-PAGE) preparative method was developed and used to purify rabbit and human defensins. With it, we identified two post-translationally modified forms of rabbit defensins NP-1 and NP-2, and purified a processed RANTES (beta-intercrine) peptide from leukophoresed human leukocytes. CAU-PAGE afforded approximately 70% recovery of rabbit defensin NP-5. The recovered defensins were not N-terminally modified, and their in vitro antimicrobial activity was equivalent to that of defensins purified by previously described chromatographic methods. Since CAU PAGE is performed under nonreducing conditions, it should be especially useful for purifying cationic peptides with intramolecular disulfide bonds, such as defensins and alpha or beta-intercrines. PMID- 8452237 TI - A Coomassie brilliant blue G-250-based colorimetric assay for measuring activity of calpain and other proteases. AB - The activity of cytosolic calcium-dependent neutral protease (calpain) is commonly measured using casein as a substrate. A novel, modified caseinolysis assay is now developed. It involves incubation of calpain with substrate casein, followed by removal of an aliquot to which Coomassie brilliant blue G-250 dye reagent is added. The assay is based on the observation that the dye interacts only with protein but not the proteolytic products (small peptides and amino acids). Unlike the existing caseinolysis assay, this novel assay does not require separation of substrate from products and measurement is done in the visible range (595 nm). It is also more sensitive than existing colorimetric assays which use dye-conjugated protein substrates. The assay can also be used to measure the activity of other proteases such as trypsin and papain. PMID- 8452238 TI - Measurement of radiolabeled lactate production using lactate monooxygenase. PMID- 8452239 TI - A modified unique site elimination plasmid mutagenesis procedure utilizing standard calcium chloride transformations. PMID- 8452240 TI - A rapid protocol for the purification of plasmid DNA template suitable for DNA sequencing. PMID- 8452241 TI - Fourier transform mass spectrometry of high-mass biomolecules. PMID- 8452242 TI - Blood lead measurement takes the direct approach. PMID- 8452243 TI - Forensic toxicology. PMID- 8452244 TI - Amperometric sensors for peroxide, choline, and acetylcholine based on electron transfer between horseradish peroxidase and a redox polymer. AB - Amperometric sensors have been developed for hydrogen peroxide, choline, and acetylcholine by immobilization of horseradish peroxidase, (HRP), choline oxidase, and acetylcholinesterase in a cross-linked redox polymer deposited on glassy carbon electrodes. Peroxide sensors, prepared by immobilization of HRP alone, gave detection limits of 10 nM and a linear response up to ca. 1 mM. Coimmobilization of HRP and glucose oxidase was used to establish the feasibility of highly efficient bienzyme sensors at low substrate levels. Replacing glucose oxidase with choline oxidase produced sensors with submicromolar detection limits and a linear response up to 0.8 mM. Addition of acetylcholinesterase to the sensors generated a relatively small response to acetylcholine that demonstrates the feasibility of trienzyme sensors. At low substrate concentrations, no loss in sensitivity during a 1-day experiment was observed. The response times of these sensors are all less than 30 s with 2-s response times achieved in some cases. PMID- 8452245 TI - Separation of amino acid homopolymers by capillary gel electrophoresis. AB - Gel-filled capillaries utilizing highly concentrated and moderately cross-linked acrylamide-type gels in capillary electrophoresis were successfully applied to the separation of the individual oligomers of various poly(amino acids). Mixtures of both anionic and cationic nature were adequately resolved. While UV detection at 220 nm was mostly utilized, the polyanions with N-terminal groups can also be tagged with 3-(4-carboxybenzoyl)-2-quinolinecarboxaldehyde (CBQCA) for a more sensitive detection by a laser-induced fluorescence detector. PMID- 8452246 TI - Comparison of covalent and noncovalent labeling with near-infrared dyes for the high-performance liquid chromatographic determination of human serum albumin. AB - Noncovalent and covalent methods of labeling protein with near-infrared polymethine cyanine dyes were compared for use in analyzing human serum albumin (HSA) by high-performance liquid chromatography (HPLC) with near-infrared absorbance detection. While noncovalent labeling was faster than covalent labeling and took place in the physiological pH range, covalent labeling was more stable under conditions encountered in many of the widely used types of HPLC. Covalently labeled HSA protein peaks indicated uniform labeling of amino groups at both hydrophilic and hydrophobic binding sites, while noncovalent labeling showed a preference for hydrophobic binding sites. PMID- 8452247 TI - Assay of radiographic contrast agents in mice plasma and testes by high performance liquid chromatography. AB - A new buffer system is reported for the analysis of radiographic contrast agents (RCAs) sodium meglumine diatrizoate, iohexol, and iopamidol in mice plasma and testes, on a reversed-phase HPLC with UV detection. The buffer consisting of 0.1 M NaH2PO4, 0.2 mM Na2EDTA adjusted to pH 3.1 with orthophosphoric acid and 2.5 5.0% acetonitrile (v/v) resolved RCA peaks for clear quantitation. The main advantages of this system are the ambient temperature of operation and direct sample injection without prior sample purification as required in the earlier procedures. Using this procedure, uptake and clearance kinetics of these RCAs were studied in mice plasma and testes, following iv injections via tail veins. The plasma levels of all the RCAs reached maxima between 5 and 15 min and dropped down sharply. At the end of 12 h they were virtually undetected (detection limits 0.64-0.71 micrograms/mL). The testicular levels also showed a similar trend and reached undetectable levels after 4 h. There were no signs of metabolism of these RCAs in plasma or testes. The present clearance kinetics in plasma compares very well with earlier reports of non-HPLC methods of assay. PMID- 8452248 TI - Liquid-phase binding assay of human chorionic gonadotropin using high-performance liquid chromatography. AB - A new enzyme immunoassay technique (LBA: liquid-phase binding assay) to examine the characteristics of liquid-phase antigen-antibody reactions is described. Antigen (human chorionic gonadotropin: hCG) and peroxidase (POD)-labeled anti-hCG monoclonal antibody (Fab'-POD) solutions were mixed, incubated, and analyzed directly by gel filtration high-performance liquid chromatography with postcolumn enzyme activity measurement. Using the system, bound (hCG-Fab'-POD) and free (Fab'-POD) forms of enzyme-labeled antibody were separated by their molecular mass difference, and the POD activity of the conjugate was determined fluorophotometrically. All analytes became bound upon addition of excess Fab' POD, because reaction conditions in a liquid phase could be easily altered. Thus, hCG molecule could be measured via the activity of one POD molecule. And the liquid-phase antibody reaction was very fast and quantitative. On the basis of this stoichiometric relationship, equilibrium and rate constants, optimum pH, and temperature effects were easily examined. The method is simple and convenient for examination of the antigen-antibody reaction and is applicable for antigen assays requiring an accurate definition of concentrations. PMID- 8452249 TI - Determination of total mercury in waters and urine by flow injection atomic absorption spectrometry procedures involving on- and off-line oxidation of organomercury species. PMID- 8452250 TI - Surfactant replacement for respiratory failure: lessons from the neonate. PMID- 8452251 TI - Constant versus optimal plasma concentrations. PMID- 8452252 TI - Pituitary apoplexy and the conflicting perioperative goals of anticoagulation and hemostasis. PMID- 8452253 TI - Prevention of respiratory failure after hydrochloric acid aspiration by intratracheal surfactant instillation in rats. AB - Because the surfactant system probably is involved in the pathophysiology of respiratory failure caused by hydrochloric acid (HCl) aspiration, we investigated the effects of different ventilation strategies and intratracheal surfactant instillation at different time intervals on the course of pulmonary gas exchange after HCl aspiration in rats. In this study rats were anesthetized and mechanically ventilated via a tracheostomy. Respiratory failure was induced by intratracheal instillation of 3 mL/kg 0.1 N HCl. Animals (n = 49) were divided into nine groups: Groups 1 and 2 through 9 were ventilated with peak airway pressure/positive end-expiratory pressure of 14/2 and 26/6 cm H2O, respectively; Groups 3 and 4 received surfactant (200 mg/kg) intratracheally, 1 and 10 min after HCl aspiration; Groups 5 and 6 received saline, 1 and 10 min after HCl aspiration; Groups 7 and 8 received surfactant, 60 and 90 min after HCl aspiration; Group 9 received saline instead of HCl. Gas exchange deteriorated in Groups 1, 2, 5, 6, 7, and 8, whereas respiratory failure could be prevented in Groups 3 and 4. After deterioration of gas exchange, surfactant treatment prevented further decrease of PaO2 values in Group 7, whereas no effect on gas exchange was observed in Group 8; intratracheal instillation of saline had no effect on gas exchange (Group 9). These results suggest that surfactant should be given as early as possible after aspiration of gastric contents to prevent development of respiratory failure. PMID- 8452254 TI - Selective application of cardiopulmonary resuscitation improves survival rates. AB - This study is a retrospective review of all patients who died without cardiopulmonary resuscitation (CPR) or who sustained a sudden cardiopulmonary arrest in the hospital and received CPR during a 2-yr period at a large medical center. Based on a review of Current Procedural Terminology codes, patients were classified into one of the ten disease categories: multiple medical problems, acute disease, procedure-related, congenital disease, neoplasm, metastatic neoplasm, trauma, burn, acquired immunodeficiency syndrome, and dementia. A total of 1206 patient deaths without a CPR effort were identified. CPR was administered to another 550 patients who had a sudden cardiopulmonary arrest, of which 71% survived the resuscitative attempt initially, but only 25% survived CPR until discharge from the hospital. CPR was applied less frequently than the mean in the metastatic neoplasm (P < 0.0001), trauma (P = 0.013), and dementia (P = 0.0003) groups and more frequently in the acute disease (P < 0.0001) and procedure related (P < 0.0001) groups. Survival to discharge from the hospital was more frequent than the mean in the congenital disease group (P = 0.0004) and less frequent in the neoplasm group (P = 0.0425). The other groups had survival rates comparable to the mean. Patients 70 yr of age and older were less likely to receive CPR than those younger than 70 (P < 0.0001). However, if they did receive CPR, they were just as likely to survive to discharge from the hospital as the younger patients (P = 0.3404).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452255 TI - Effect of angiotensin II on myocardial blood flow and acid-base status in a pig model of cardiopulmonary resuscitation. AB - The effect of angiotensin II on myocardial blood flow and acid-base status during cardiopulmonary resuscitation (CPR) was assessed. Fourteen pigs were allocated randomly to receive either 0.9% saline (n = 7) or 0.05 mg/kg angiotensin II (n = 7) after 4 min of ventricular fibrillation and 3 min of open-chest CPR. Total myocardial blood flow (measured with radiolabeled microspheres) before, 90 s, and 5 min following drug administration was 74 +/- 18, 62 +/- 12, and 54 +/- 11 mL.min-1 x 100g-1 (mean +/- SD) in the control, and 72 +/- 17, 125 +/- 25, and 74 +/- 20 mL.min-1 x 100 g-1 in the angiotensin II group (P < 0.001 at 90 s and P < 0.05 at 5 min). The PCO2 of coronary venous blood at 90 s after drug administration was 82 +/- 8 mm Hg in the control group as compared to 47 +/- 9 mm Hg in the angiotensin II group (P < 0.001). Only three of the seven control group animals could be resuscitated successfully, whereas all of the angiotensin II treated pigs survived the 1-h observation period (P < 0.05), during which neither arterial hypertension nor bradycardia was observed. Angiotensin II was associated with an improvement of myocardial blood flow during CPR and short-term resuscitation success. The increase in myocardial perfusion is associated with a lower coronary venous PCO2 and a higher coronary venous pH. The authors conclude that angiotensin II administration facilitated cardiopulmonary resuscitation. PMID- 8452256 TI - Effects of adenosine on renal function and central hemodynamics after coronary artery bypass surgery. AB - In the early postoperative period after coronary artery bypass surgery, arterial hypertension commonly occurs which requires intravenous vasodilator therapy. Purine adenosine is a potent vasodilator and when exogenously administered it decreases systemic arterial blood pressure effectively. We evaluated the effects of adenosine on central hemodynamics and renal function when used to control postoperative hypertension after coronary artery bypass grafting (CABG). Two separate series of experiments were performed postoperatively in the Intensive Care Unit (ICU). In the first study (n = 10), postoperative hypertension was controlled in the rewarming phase, with sodium nitroprusside (SNP, 1.7 +/- 0.4 micrograms.kg-1 x min-1) or adenosine (147.2 +/- 38.9 micrograms.kg-1 x min-1) to keep mean arterial systolic pressure at approximately 80 mm Hg. In the second study on a separate group of patients (n = 9), low doses of adenosine (0, 30, 60, 90, and 0 micrograms.kg-1 x min-1) were infused when the patients were normotensive and rewarmed. Central hemodynamics, urine flow (UF), renal blood flow (RBF), glomerular filtration rate (GFR), and ECG were evaluated during periods of 30 min for each drug in the first study and during each dose of adenosine in the second study. RBF and GFR were determined using standard urinary clearance methods for 51Cr-ethylenediaminetetraacetic acid and p-aminohippuric acid. In the first study, adenosine infusion, compared to SNP, decreased (A - V)O2, increased central filling pressures and heart rate, and caused a more pronounced ST segment depression. During adenosine administration RBF (-44%), GFR (-52%), and UF (-76%) decreased, while renal vascular resistance and filtration fraction (FF) were unaltered compared to data obtained during SNP infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452257 TI - Vasodilation with adenosine or sodium nitroprusside after coronary artery bypass surgery: a comparative study on myocardial blood flow and metabolism. AB - The effects of adenosine and sodium nitroprusside (SNP) on central hemodynamics and myocardial blood flow and metabolism were investigated postoperatively after elective coronary artery bypass (CABG) surgery in ten sedated and mechanically ventilated patients in the intensive care unit. During three consecutive 15-min periods, SNP (0.8 +/- 0.1 micrograms.kg-1 x min-1), adenosine (88.9 +/- 13.3 micrograms.kg-1 x min-1), and then again SNP (0.7 +/- 0.1 micrograms.kg-1 x min 1) were infused to control postoperative hypertension at a mean arterial pressure of approximately 80 mm Hg. Systemic and pulmonary hemodynamics and global (coronary sinus flow, CSF) as well as regional (great cardiac vein flow, GCVF) myocardial blood flow and metabolic variables were measured. During adenosine infusion, in comparison to SNP, heart rate was unchanged, stroke volume index and cardiac index increased (24% and 32%, respectively), and the systemic vascular resistance index decreased (-26%). Mean pulmonary arterial pressure (24%) as well as pulmonary capillary wedge pressure (27%) and central venous pressure (18%) were higher with adenosine compared to SNP. Adenosine also increased CSF and GCVF (108% and 103%, respectively) without altering the CSF/GCVF flow ratio compared to SNP. Furthermore, adenosine increased the coronary oxygen content (51%) and decreased the arterio-great cardiac vein oxygen content difference (-48%) without changing regional myocardial oxygen consumption, indicating a more pronounced hyperkinetic myocardial circulation compared to SNP. In addition, adenosine infusion decreased arterial PO2 (-11%) and increased the intrapulmonary shunt fraction (57%). The PR interval time of the electrocardiogram was prolonged (12%) and the ST segment was more depressed during adenosine infusion compared to SNP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452258 TI - Fibrinolytic and hemorheologic alterations during and after elective aortic graft surgery: implications for postoperative management. AB - The hemorheologic and fibrinolytic variables of 15 patients undergoing elective aortic graft surgery were investigated before, during, and after surgery. During the operation, a relative hemodilution was induced intentionally by an infusion of crystalloids and albumin. This led to a decrease in hematocrit (35.5 +/- 6.3- >31.8 +/- 5.6%, P < 0.01), fibrinogen, and platelets, as well as a decrease in fibrinolysis (Euglobulin Clot Lysis Time increases 246 +/- 52-->300 +/- 46 min and fast-acting plasminogen activator inhibitor 1 [PAI-1] activity increases 10.5 +/- 6.9-->15.1 +/- 9 IU/mL, P < 0.01). There was also specific rheologic impairment with a dissociation of erythro-aggregates (primary aggregation time 3.37 +/- 2.63-->7.18 +/- 7.2 s). Tissue-type plasminogen activator (t-PA) antigen was only increased just after surgery (8.3-->14.5 ng/mL, P < 0.01). During the first postoperative week, the acute-phase response subsided. This was accompanied by an increase in fibrinogen, von Willebrand factor antigen, and plasma viscosity (1.33 +/- 0.13-->1.49 +/- 0.13 mPa x s, P < 0.01). Hematocrit and the extrinsic fibrinolytic system (t-PA/PAI) returned to baseline values, whereas intrinsic fibrinolysis remained altered (the Euglobulin Clot Lysis Time, reflecting total activity of plasminogen activators, was still increased). Postoperative management may benefit from a recognition of these two distinct phases induced by surgery. The acute-phase reaction of the first postoperative week is an added vascular risk factor and requires a specific therapeutic approach. PMID- 8452259 TI - Prolonged administration of isoflurane to pediatric patients during mechanical ventilation. AB - We undertook a prospective study of the effectiveness and potential toxicities of isoflurane sedation in pediatric patients undergoing mechanical ventilation who required large doses of opioids for sedation were considered eligible. Ten patients (ages 3 wk to 19 yr) received continuous isoflurane sedation for a mean duration of 131 minimum alveolar concentration (MAC)-hours (range 13-497 MAC hours). The mean peak inorganic fluoride (F-) concentration was 11.0 microM, and the highest F- concentration was 26.1 microM after 441 MAC-hours. Only one patient had a measured F- concentration greater than 20 microM. No abnormalities were noted in serum creatinine or osmolality. Creatinine clearances were available for five patients who received a mean of 193 MAC-hours of isoflurane (range 33-497 MAC-hours), and only one patient had a persistent decrease from baseline of more than 20%. Five patients demonstrated an abstinence syndrome which consisted of nonpurposeful movements and extreme agitation. All of these patients had received at least 70 MAC-hours of isoflurane. Our experience indicates that isoflurane can effectively provide sedation to pediatric patients for prolonged periods without significant adverse effects on cardiovascular, hepatic, or renal function. PMID- 8452260 TI - Complications and fiberoptic assessment of size 1 laryngeal mask airway. AB - In pediatric practice, complications due to the laryngeal mask airway (LMA) have been studied with size 2 LMA, but not with size 1 LMA. We, therefore, compared prospectively the complications induced by LMA size 1 and 2 in 141 children aged 21 days to 11 yr. Intraoperative and lowest SpO2 values after removal of LMA were recorded. The following complications were recorded: cough, laryngospasm, bronchospasm, apnea, and airway obstruction. In 14 patients in the size 1 LMA group and 26 patients in the size 2 LMA group, pharyngolaryngeal structures were checked with fiberoptic examination. The number of attempts, complications, intraoperative SpO2, and lowest SpO2 values were similar when using size 1 and size 2 LMA. Fiberoptic examination of size 1 LMA showed a high incidence of impinging of the epiglottis in the LMA bars without airway obstruction. In conclusion, there was no difference in the complication rate between the two pediatric sizes of LMA when used in pediatric patients. PMID- 8452261 TI - Supraclavicular nerve block: anatomic analysis of a method to prevent pneumothorax. AB - Supraclavicular nerve blocks are technically easy to perform, but may be associated with pneumothorax. The objective of this study is to define the parasagittal anatomy important to our modified technique of supraclavicular nerve block designed to decrease the incidence of pneumothorax and to determine whether this technique is anatomically sound. Two cadaver specimens were studied. One embalmed specimen was dissected to establish the relationship of the brachial plexus to our modified needle entry site. The neck and upper thorax of an unembalmed cadaver were frozen, and parasagittal serial sections were made to establish the relationship of the brachial plexus to surface features and the chest cavity. Additionally, 12 volunteers underwent magnetic resonance (MR) imaging and anatomic measurements of their supraclavicular anatomy important to our modified block. MR imaging showed that in no instance using our modified technique was the lung contacted by the simulated needle before entering either the subclavian artery or contacting the brachial plexus. Our technique has been used in more than 110 patients without pneumothorax. The combination of our cadaver and magnetic resonance data suggests that our plumb-bob technique of supraclavicular nerve block is anatomically sound and may minimize the development of pneumothorax during supraclavicular block. PMID- 8452262 TI - Anatomic and biomechanical properties of human lumbar dura mater. AB - Determinants of dural defects subsequent to deliberate or accidental dural puncture include the equipment, techniques, and the inherent anatomic and biomechanical properties of dura mater. These properties were studied in specimens of human and canine lumbar dura mater in an attempt to delineate the structure of the tissue and to characterize its behavior in biomechanical terms. Human dura had a longitudinal orientation on gross appearance, and was confirmed microscopically to be composed of longitudinal lamella of collagen and elastin fibers. Longitudinal tensile strength and stiffness were greater than transverse tensile strength and stiffness, which is consistent with the dura's apparent anatomic structure and functional requirements. Additional biomechanical testing of the dura demonstrated the property of relaxation which is a characteristic of a viscoelastic material. Significant differences were observed between human and canine dural properties, suggesting limited value of this animal model. Integration of these observed anatomic and biomechanical properties of the lumbar dura provides a greater understanding of dural puncture and may explain previous and often confusing clinical and experimental findings. PMID- 8452263 TI - Effect of phenylephrine bolus administration on left ventricular function during high thoracic and lumbar epidural anesthesia combined with general anesthesia. AB - The effect of phenylephrine (PHE) boluses on left ventricular (LV) function was examined in patients without cardiovascular disease who developed arterial hypotension during high thoracic epidural anesthesia (TEA) combined with general anesthesia (GA) (group 1) or lumbar epidural anesthesia (LEA) combined with GA (group 2). LV function was assessed by transesophageal echocardiography (TEE) before and after central venous injection of 1 microgram/kg PHE. Fractional diameter shortening (FDS), end-systolic wall stress (ESWS), and rate-corrected velocity of circumferential fiber shortening (mVcfc) were determined. PHE effectively restored arterial blood pressure in both groups with a peak effect between 30 and 45 s after injection. FDS was reduced from 38% to 25% (mean, P < 0.01) in group 1 and remained unchanged in group 2. ESWS increased from 70 to 143 x 10(3) dyne.cm-2 (P < 0.01) and from 57 to 86 x 10(3) dyne.cm-2 (P < 0.05), in groups 1 and 2, respectively. mVcfc was significantly reduced from 1.11 to 0.80 circ/s (P < 0.05) in group 1 and was not altered in group 2. The authors conclude that PHE given as an intravenous bolus to patients under high TEA plus general anesthesia causes a transient impairment of LV function. PMID- 8452264 TI - Glucose in epidural catheter aspirate. AB - Frequently fluid may be aspirated from epidural catheters during epidural anesthesia/analgesia. This fluid may be either cerebrospinal fluid or local anesthetic. Several methods for differentiation of the two fluids have been recommended. In this study, the reliability of the "glucose test" was analyzed. Epidural catheters were inserted into 43 healthy, nondiabetic parturients and then gently aspirated. Aspirate was tested for glucose using glucose oxidase paper. Positive aspirates were assessed for the presence of prealbumin, which is a protein marker for cerebrospinal fluid. Of the patients undergoing cesarean section, 17 of 27 patients yielded a glucose-positive aspirate, and of the patients undergoing labor analgesia, 6 of 16 patients were found to be positive for glucose. None of these patients developed total spinal anesthesia or postdural puncture headache. Visually, none of the aspirates were significantly blood-tinged, blood being a possible source of glucose. When the glucose-positive aspirates were subjected to immunoelectrophoresis, 6 of 7 aspirates revealed a prealbumin band. In conclusion, the glucose test for cerebrospinal fluid may be misleading. The source of this glucose may be normal cerebrospinal fluid drainage into the epidural space. PMID- 8452265 TI - The effect of head-down tilt on arterial blood pressure after spinal anesthesia. AB - We examined the usefulness of 10 degrees head-down tilt for hypotension after spinal block. Two different investigations were performed, one employing head down tilt after arterial blood pressure had decreased (n = 40), and the other using a prophylactic tilt (n = 50). When the head-down tilt was applied to treat hypotension after spinal block (n = 40), arterial blood pressure increased only in patients whose systemic blood pressure decreased more than 30% from the control (severe hypotension group, n = 11). However, even in the severe hypotension group, systolic blood pressure did not increase in two patients after 10 degrees head-down tilt. When the head-down tilt was performed immediately after spinal block (n = 24), the changes in systolic blood pressure were the same as in the horizontal group (n = 26). The cephalad spread of analgesia at 20 min after spinal block was higher, however, in the head-down tilt group (T3.8 +/- 1.6) than the horizontal group (T5.2 +/- 1.9). From these results we conclude that head-down tilt for hypotension after spinal block increases arterial blood pressure only for severe hypotension, and that prophylactic head-down tilt has no effect in maintaining blood pressure. PMID- 8452266 TI - Toxicity of bupivacaine encapsulated into liposomes and injected intravenously: comparison with plain solutions. AB - The acute central nervous system and cardiac toxicities of 0.25% bupivacaine, without adrenalin, encapsulated in multilamellar liposomes were compared with 0.25% plain solutions with and without adrenalin after intravenous infusion at a rate of 0.15 mg.kg-1 x min-1 with an increase of 0.036 mg.kg-1 x min-1 every 10 min. Three groups of six anesthetized, unventilated rabbits were studied. The doses of bupivacaine (in mg.kg-1) which produced seizure, ventricular tachycardia, and asystole were determined. The doses of bupivacaine inducing seizure and ventricular tachycardia were significantly higher for liposomal bupivacaine than for the two plain solutions. A statistical comparison of the cumulative lethal doses of bupivacaine 0.25% with adrenalin and of liposomal bupivacaine led to a P = 0.06. Adrenalin did not modify the systemic toxicity of the local anesthetic. This study showed a reduction of nervous and cardiac toxicity of bupivacaine encapsulated in multilamellar liposomes when infused intravascularly. PMID- 8452267 TI - Preprogrammed infusion of alfentanil to constant arterial plasma concentration. AB - A variable rate infusion regimen, designed to rapidly achieve and maintain a target arterial concentration (CT) of 100 micrograms.L-1 of alfentanil, was developed using the method of Plasma Drug Efflux. This method uses a series of clearance values (Ep), calculated as the ratio of instantaneous infusion rate/arterial plasma drug concentration normalized to lean body mass (LBM), at various sampling times during a suboptimal infusion regimen. Values of Ep are used to calculate an infusion rate versus time profile to achieve CT, and the process is repeated in consecutive small groups of subjects to yield an optimal result, i.e., it is an iterative process. Thirty-three adult surgical patients were given alfentanil during anesthesia for approximately 1 h before cardiopulmonary bypass. In an initial group of four patients, who received a simple two-stage infusion, plasma alfentanil concentration was measured at frequent intervals and Ep(L.min-1.kg LBM-1) was estimated at each sampling time. The calculated infusion-rate-versus-time profile to produce CT was obtained from the product Ep x CT for each time point and was transferred to the read-only memory of a computerized infusion pump. This new variable infusion profile was used in four patients, and the process was repeated in three further groups of 5, 8, and 12 patients using infusion profiles calculated from the previous group. Each set of concentration data was assessed by calculating the performance error (PE), the median performance error (MDPE), i.e., bias, and the median absolute value of PE (MDAPE), i.e., inaccuracy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452268 TI - Right ventricular function during orthotopic liver transplantation. AB - Right ventricular (RV) function was assessed in 20 patients undergoing orthotopic liver transplantation to determine its role in the hemodynamic instability frequently seen during this procedure. A modified pulmonary artery catheter equipped with a fast response thermistor was used to determine RV ejection fraction (EFrv), allowing for calculation of RV end-diastolic volume index (EDVIrv, as the ratio of stroke index [SI] to EFrv) and RV end-systolic volume index (ESVIrv, as the difference between EDVIrv and SI). The above hemodynamic measures were taken during dissection for hepatectomy (stage I), during the anhepatic stage (stage II), and after reperfusion of the grafted liver, the neohepatic stage (stage III). No patient had pulmonary hypertension during the study interval. No correlation was observed between right atrial pressure (Pra) and EDVIrv, indicating that Pra is a less reliable clinical indicator of RV preload. RV function appeared to be well preserved throughout the procedure, as indicated by a relatively constant and supranormal EFrv, although a small and probably clinically unimportant decrease in EFrv was observed during the anhepatic stage (0.52, 0.50, and 0.55 during stages I, II, and III, respectively). There was a strong correlation between SI and EDVIrv for pooled data over a wide range of EDVIrv (60-185 mL.m-2). Although unstable central blood temperature precluded the determination of EFrv within the first 5 min after reperfusion, RV function was unaltered otherwise during uncomplicated orthotopic liver transplantation using venovenous bypass, indicating that orthotopic liver transplantation per se is not associated with significant RV dysfunction. PMID- 8452269 TI - Plasma laudanosine levels in patients given atracurium during liver transplantation. AB - Atracurium, a nondepolarizing muscle relaxant, does not depend on the liver for clearance, but its principal metabolite, laudanosine, is eliminated primarily by the liver and is potentially neurotoxic. We measured atracurium and laudanosine levels in 15 adult patients during the three stages of liver transplantation to assess the effect of major impairment of liver function. Atracurium was given in a bolus dose of 0.5 mg/kg followed by continuous infusion at a rate adjusted to maintain 95-99% of total neuromuscular block, as judged by train of four response to facial nerve stimulation. Atracurium levels remained constant at 1.4-1.8 micrograms/mL during the 180-min preanhepatic and 75-min anhepatic stages but decreased to a mean of 1.0 microgram/mL by the end of the 180-min postanhepatic stage. In contrast, laudanosine levels increased during each stage, being 0.40 +/ 0.18, 0.50 +/- 0.22, and 0.43 +/- 0.16 micrograms/mL after the preanhepatic, anhepatic, and postanhepatic stages, respectively. The highest individual value recorded was 1.02 microgram/mL. We conclude that, despite increases in laudanosine levels during each stage of liver transplantation in patients receiving atracurium, those levels are only about one-tenth of the maximum values previously reported in humans. PMID- 8452270 TI - Perioperative liver graft function: the role of oxygen transport and utilization. AB - To assess the evolution of satisfactory neohepatic graft function or failure, hemodynamic variables, along with data for oxygen delivery and utilization, were analyzed retrospectively in 99 patients undergoing orthotopic liver transplantation. Caval cross-clamping without venovenous bypass initiated a series of hemodynamic events, characterized by decreases in pulmonary artery pressures, cardiac output, and arterial pressures and increases in systemic vascular resistance, with reciprocal changes after unclamping. Concerning oxygen transport, the increased oxygen delivery after caval unclamping led to increases of mixed venous oxygen tension, decreases of oxygen extraction, and the arteriovenous oxygen content difference. The most striking result, however, was that with similar values for oxygen delivery, the patients with primary nonfunction (n = 9) had both lower anhepatic oxygen consumption, much smaller increases in oxygen consumption, and lower ratios of oxygen extraction during reperfusion of the liver than the patients with normal initial graft function (n = 90). Thus, distinct increases in total body oxygen consumption were found to be indicative of the onset of hepatocellular function and satisfactory neohepatic graft function. The authors conclude that perioperative measurements of whole body oxygen consumption are important in reflecting early allograft viability during orthotopic liver transplantation without anhepatic venovenous bypass. PMID- 8452271 TI - The effect of two levels of hypotension on intraoperative blood loss during total hip arthroplasty performed under lumbar epidural anesthesia. AB - The degree of induced hypotension necessary to achieve a significant reduction in intraoperative blood loss has never been defined. Forty patients undergoing primary total hip arthroplasty during epidural anesthesia by a single surgeon were randomly assigned to have mean arterial pressure maintained at 50 +/- 5 mm Hg or 60 +/- 5 mm Hg throughout surgery. Intraoperative blood loss was 179 +/- 73 mL in the 50 mm Hg group and 263 +/- 98 mL in the 60 mm Hg group (P = 0.004). Subjectively, there was more bleeding during surgery in the 60 mm Hg group during dissection of the hip joint (P = 0.0026) and while reaming the acetabulum (P = 0.0001) and femur (P = 0.0001). No difference in transfusion requirements, postoperative hematocrit, or duration of surgery was noted. A difference in mean arterial blood pressure of 10 mm Hg from 50 to 60 mm Hg during surgery for total hip arthroplasty under epidural anesthesia has a measurable effect on intraoperative blood loss. PMID- 8452272 TI - Transient negative dromotropic effects of catecholamines on canine Purkinje fibers exposed to halothane and isoflurane. AB - The time-dependent effects of catecholamines in combination with volatile anesthetics on conduction velocity of canine Purkinje fibers were investigated to evaluate a controversial older hypothesis that the arrhythmogenic interaction between epinephrine and halothane may involve abnormal conduction. Two groups of 12 in vitro preparations were stimulated at 150 beats/min. In the first group, 5 microM epinephrine by itself did not alter conduction velocity over a 10-min period from a control mean value of 1.97 +/- 0.08 m/s. However, 5 microM epinephrine, in the presence of either 0.4 mM halothane or 0.4 mM isoflurane, reduced conduction velocity (P < or = 0.01) by about 10-15% within 3-5 min, with recovery toward control by 10 min. The mean conduction velocity at the 4th minute of exposure, in the presence of halothane and epinephrine (1.65 +/- 0.11 m/s), was lower (P < or = 0.01) than that obtained in the presence of isoflurane and epinephrine (1.74 +/- 0.07 m/s). In the second group, both 5 microM norepinephrine and 5 microM epinephrine, in the presence of either anesthetic, depressed conduction velocity (P < or = 0.01) with a similar time course. The reduction of conduction velocity with norepinephrine was less (P < or = 0.01) than that with epinephrine, and again the decreases of conduction velocity were larger (P < or = 0.01) with 0.4 mM halothane than 0.4 mM isoflurane.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452273 TI - Induction of anesthesia with sevoflurane, nitrous oxide, and oxygen: a comparison of spontaneous ventilation and vital capacity rapid inhalation induction (VCRII) techniques. AB - In this study, the vital capacity rapid inhalation induction of anesthesia (VCRII) technique and the conventional spontaneous inhalation induction technique, each using 4.5% sevoflurane in nitrous oxide and oxygen, were compared. The VSRII group (n = 32) and conventional group (n = 32) were each tested on unpremedicated volunteers. VCRII required only half the time of conventional inhalation induction (54 s and 108 s, respectively), and was not associated with cardiovascular instability. Each of the two techniques was found acceptable by most of the volunteers studied (more than 80%). However, sevoflurane is best used with the VCRII technique because VCRII resulted in fewer excitement movements that could lead to severe complications and pronounced excitement. PMID- 8452274 TI - Enflurane and isoflurane reduce reperfusion dysfunction in the isolated rat heart. AB - We evaluated the possible cardioprotective effects of enflurane (E) and isoflurane (I) in isolated rat hearts subjected to 40 min normothermic arrest. After reperfusion, hearts were stimulated with adrenaline to evaluate their systolic reserves. In hearts not receiving I or E, adenosine triphosphate (ATP) was reduced from 23.0 +/- 0.8 to 9.3 +/- 1.1 mumol/g dry weight (means +/- SEM; P < 0.001) after arrest. This was associated with a significant reduction in ventricular work (Wt) from 13.6 +/- 0.7 to 1.6 +/- 0.7 mW (P < 0.001). Adrenaline partially restored Wt but not the ATP. E and I given only during normothermic arrest (in the cardioplegic solution) resulted in reductions in ATP similar to the hearts not receiving the drugs. However, on reperfusion and subsequent administration of adrenaline, hearts subjected to the anesthetic drugs performed as well as hearts before arrest. For example, in hearts not exposed to I or E, the Wt after the elective arrest was 1.55 +/- 0.05% (mean +/- SEM) of the pre arrest value. This was significantly less than hearts exposed to either one of the inhalational agents (40.02 +/- 3.49% of the pre-arrest value; P < 0.0001). Adrenaline improved function in hearts which did not receive I or E to 55.02 +/- 12.80% of the pre-arrest value, but this was significantly less than the Wt performed by the hearts exposed to the anesthetic agents (122.67 +/- 7.78% of pre arrest value; P < 0.001). This beneficial effect of I and E during reperfusion probably is mediated by the effect of the anesthetic agents on Ca2+ slow channels. The effect could not be ascribed to depression of global myocardial contractile function associated with I and E. PMID- 8452275 TI - Memory facilitation by posttraining exposure to halothane, enflurane, and isoflurane in ddN mice. AB - The effect of low and high concentrations of halothane, enflurane, and isoflurane on posttraining memory function was studied in male ddN mice. Mice were trained to escape an aversive electric foot shock as an unconditioned stimulus within 3 s after being exposed to light and a buzzer as a conditioned stimulus. Immediately after training (first session: 30 trials), the animals were exposed to halothane, enflurane, or isoflurane for 120 min and then were tested again on the avoidance task (second session: 30 trials) 22 h after cessation of exposure. The performance ratios, [B/A] (i.e., A is the score in the first session, and B the score in the second) were compared between the anesthetized groups and their respective control (nonanesthetized) groups. Mean performance ratios in the control groups ([B/A]c) ranged from 136.8% to 163.9% and those in the anesthetized groups ([B/A]a) ranged from 151.4% to 174.7%. [B/A] in each anesthetized group exceeded [B/A] in its corresponding control group. [B/A]a significantly exceeded [B/A]c by 13.1% in the 1.23 minimum alveolar concentration (MAC) enflurane group (P < 0.05) and by 12.4% in the 0.29 MAC isoflurane group (P < 0.05). These results suggest that posttraining exposure to volatile anesthetics facilitates memory. PMID- 8452276 TI - Anesthetic interaction between midazolam and halothane in humans. AB - The present study was undertaken in humans to determine the anesthetic efficacy of midazolam in terms of its ability to reduce halothane minimum alveolar anesthetic concentration (MAC). Fifty women scheduled for simple or radical hysterectomy were allocated randomly to one of four groups; group A was given no midazolam as a control; groups B, C, and D were given midazolam intravenously by a bolus of 0.1, 0.2, and 0.4 mg/kg followed by infusion of 1, 2, and 4 micrograms.kg-1 x min-1, respectively. Halothane MAC was 0.78%, 0.47%, 0.38%, and 0.23% at mean serum midazolam concentrations of 0, 134, 250, and 539 ng/mL in groups A, B, C, and D, respectively. The interaction between halothane and midazolam in the anesthetic efficacy conformed to an exponential fit. The results indicate that midazolam produces marked reduction of halothane MAC in humans at serum concentrations lower than that required to cause sleep. Lastly, midazolam's potentiation of halothane has a saturated nature. PMID- 8452277 TI - An analysis of the duration of fentanyl and its metabolites in urine and saliva. AB - This study was undertaken to determine if metabolites of fentanyl might be useful in the detection and monitoring of substance abuse. The presence of fentanyl and two of its metabolites in the urine and saliva of seven female patients receiving small doses (110 +/- 56 micrograms) of fentanyl was studied up to 96 h from the time of administration. Fentanyl and its two metabolites (norfentanyl and despropionylfentanyl) were extracted from samples and analyzed by gas chromatography/mass spectrometry. Unchanged fentanyl was detectable in urine in all patients immediately postoperatively and in 3 of 7 patients at 24 h. By 72 h, fentanyl was undetectable. Norfentanyl was present in larger quantities than fentanyl immediately postoperatively and was detected in all patients at 48 h and in 4 of 7 patients at 96 h. Despropionylfentanyl was not detected in any of the urine specimens tested. Neither fentanyl nor its metabolites could be detected consistently at any time in saliva. Saliva testing does not appear to be a viable alternative to urine testing based on this study. Urinary norfentanyl might be considered as the substance of choice when testing for fentanyl abuse. PMID- 8452278 TI - Pulmonary CO2 elimination during surgical procedures using intra- or extraperitoneal CO2 insufflation. AB - We examined end-tidal CO2 tension (PETCO2) and pulmonary CO2 elimination of CO2 (VECO2) during CO2 insufflation under general anesthesia for three surgical procedures: gynecologic laparoscopy (intraperitoneal CO2 insufflation for 43 +/- 4 min), laparoscopic cholecystectomy (intraperitoneal CO2 insufflation for 125 +/ 14 min), and pelviscopy (extraperitoneal CO2 insufflation for 45 +/- 3 min). All patients (10 in each group) underwent controlled mechanical ventilation. Oxygen consumption (VO2) and VECO2 were measured at 2-min intervals by a system using a mass spectrometer. For the three surgical procedures, VO2 remained stable, whereas VECO2 and PETCO2 increased in parallel from the 8th to the 10th min after the start of CO2 insufflation. A plateau was reached 10 min later in patients having intraperitoneal insufflation, whereas VECO2 and PETCO2 continued to increase slowly throughout CO2 insufflation during pelviscopy. During pelviscopy, the maximum increase in VECO2 and PETCO2 (76 +/- 5% and 71 +/- 7%) was significantly more pronounced than that observed during cholecystectomy (25 +/- 4% and 25 +/- 4%) and gynecologic laparoscopy (15 +/- 3% and 12 +/- 2%). The authors conclude that CO2 diffusion into the body is more marked during extraperitoneal than during intraperitoneal CO2 insufflation but is not influenced markedly by the duration of intraperitoneal insufflation. PMID- 8452279 TI - Ranitidine reverses gallamine paralysis in rats. AB - The effect of ranitidine on gallamine-induced depression of twitch tension was evaluated in urethane-anaesthetized and mechanically ventilated male Sprague Dawley rats. Gallamine was administered as an intravenous (IV) bolus and constant rate infusion in 15 rats to maintain 89 +/- 7% (SE) depression of twitch tension induced by electrical stimulation of a sciatic nerve. Ranitidine, IV at either 0.5, 1, 2.5, 5, or 10 mg/kg, was then administered into groups of three rats. Ranitidine produced an immediate dose- and serum concentration-dependent reversal (antagonism) of the twitch tension depression induced with gallamine. The reversal was observed within approximately 30 s and was maintained for 3-26 (12 +/- 2) min. The dose of ranitidine that produced 50% reversal was 2.9 +/- 0.1 mg/kg, and this reversal was associated with a ranitidine serum concentration of 5.2 +/- 0.3 micrograms/mL. Ranitidine administered alone (and without gallamine) did not alter twitch tension at either 2.5 or 20 mg/kg. In addition, ranitidine did not alter either the gallamine neuromuscular blocking concentration in serum or the serum clearance of gallamine. Ranitidine reverses the neuromuscular action of gallamine, and this effect of ranitidine is not due to a pharmacokinetic interaction between ranitidine and gallamine. PMID- 8452280 TI - Latex allergy: an emerging operating room problem. PMID- 8452281 TI - James Tayloe Gwathmey: seeds of a developing specialty. PMID- 8452282 TI - Pituitary apoplexy after coronary artery surgery. PMID- 8452283 TI - Latex allergy: failure of prophylaxis to prevent severe reaction. PMID- 8452284 TI - Pharyngeal obstruction of a reinforced orotracheal tube. PMID- 8452285 TI - Meperidine in patient-controlled analgesia: a near-fatal mishap. PMID- 8452286 TI - Enhancement of bupivacaine cardiotoxicity with cardiac glycosides and beta adrenergic blockers: a case report. PMID- 8452287 TI - Ureteroscopic removal of left ureteral lithiasis in a patient with acid maltase deficiency disease. PMID- 8452288 TI - At risk for aspiration: new critical values of volume and pH? PMID- 8452289 TI - Training in antibiotic administration. PMID- 8452290 TI - Hypotensive anesthesia and orthognathic surgery. PMID- 8452291 TI - Airway obstruction from cricoid pressure. PMID- 8452292 TI - Unusual complication of arterial catheterization. PMID- 8452294 TI - Airport novels and operating rooms. PMID- 8452293 TI - Pressure support ventilation: what is the clinical significance? PMID- 8452295 TI - Using Myotrace force transducer for monitoring great toe flexion. PMID- 8452296 TI - Retrieving an article from erroneous citation. PMID- 8452297 TI - Orogastric intubation: near-strangulation of endotracheal tube. PMID- 8452298 TI - Effects of adenosine. PMID- 8452299 TI - Interscalene block and pulmonary function. PMID- 8452300 TI - Anesthetic complications 14 hours after the use of crack cocaine. PMID- 8452301 TI - Stating the obvious. PMID- 8452302 TI - Leontiasis ossea: an unusual presentation of a difficult airway. PMID- 8452303 TI - Acidosis and [K+]. PMID- 8452304 TI - Upper airway obstruction and hypotonia. PMID- 8452305 TI - Preoperative hypoxemia. PMID- 8452306 TI - Combined mitral and aortic stenosis in a parturient: epidural anesthesia for labor and delivery. PMID- 8452307 TI - Efficacy of the FEF colorimetric end-tidal carbon dioxide detector in children. PMID- 8452308 TI - Scoliosis surgery: determinants of blood loss. PMID- 8452309 TI - Pneumothorax and supraclavicular block. PMID- 8452310 TI - Bellows failure with Drager Anesthesia Ventilator. PMID- 8452311 TI - Food additives and allergy. AB - There is ample evidence that food additives of several sorts may precipitate adverse reactions. Some of these have catastrophic potential such as sulfite sensitivity in asthmatic patients. Fortunately, asthmatic responses to a variety of additives are certainly not as prevalent as once feared, and are probably unusual. Restricted diets are of no general benefit in asthmatic patients. In contrast to asthma, urticarial or other cutaneous reactions to food additives are more common. A restricted diet for a few months' duration may be beneficial, although the mechanism through which this is achieved is unclear. Suspected food additive sensitivities are best documented by oral challenges, preferably in a double-blind manner. Challenges in asthmatic patients need to be done with patients continuing on their routine medications to avoid false positives. All care should be taken to titrate the doses and schedule the doses appropriately, since several of these agents could provoke large drops in pulmonary function. With urticarial patients, an adequate baseline of urticarial activity needs to be established before the challenges so that fluctuations in normal activity are not construed as a positive result. Despite a large number of studies evaluating the role of food additives in hyperkinesis, results are not uniform. Evidence does suggest that there is a small subset of primarily younger children in whom additives will impact on behavior. As with asthma and additives, the problem appears to be much smaller than originally postulated. PMID- 8452313 TI - Mechanical blockage of the nose. PMID- 8452312 TI - Vesiculobullous rash in a patient with systemic lupus erythematosus. PMID- 8452314 TI - Salsalate-induced pancytopenia in a patient with systemic lupus erythematosus. AB - After a patient with a history of systemic lupus erythematosus in remission was given salsalate, all of her hematologic elements, especially leukocytes, profoundly decreased within hours, although the patient was receiving steroids. She had been challenged with salsalate at an earlier date, with a similar but less impressive drop in blood counts. Granulocytotoxic antibodies persisted during this episode in contrast to declining lymphocytotoxic and anti-native DNA antibodies that accompanied a remission of systemic lupus. This is the first case of this kind occurring with salsalate therapy and may have represented preformed antibodies induced by salsalate. PMID- 8452315 TI - Possible relationship between allergic disease and infection by Giardia lamblia. AB - In order to better understand the possible relationship between allergic reactivity and infection with G. lamblia, specific IgE responses and skin test reactivity were evaluated in allergic or nonallergic Venezuelan children, with or without G. lamblia infection. Two groups of children were studied: one from our Allergy Clinic and the other from a slum area of Caracas. The total serum IgE levels in children from the slum area were significantly higher in those with intestinal helminthic parasites and giardiasis, compared with those with helminthiasis only (P < .001). In atopic children with giardiasis we also found an enhanced IgE antibody response to common environmental allergens (P < .05). As G. lamblia produces intestinal mucosal damage, we also studied the reactivity to cow milk and found that 22% of the children belonging to the low socioeconomic level demonstrated the presence of significant levels of specific IgE against this antigen. Of these milk-positive subjects, 40% were infected by G. lamblia in contrast to only 21% of the milk-negative children (P < .05). These results suggest that children with giardiasis may be exposed to greater amounts of intestinally absorbed antigens. We also studied the specific allergic response to G. lamblia, and found that in an unselected group of children of low socioeconomic level, 25% had positive skin tests, as did 50% of persons with symptomatic giardiasis. The presence of serum anti-Giardia IgE was also demonstrated in 22% of patients with giardiasis. PMID- 8452316 TI - IgE response in multiple myeloma. AB - IgE levels in sera of patients with multiple myeloma (MM) were found to be similar to those of patients with monoclonal gammopathy of unknown significance (MGUS) and to normal controls. This is in contrast to the significant depression in the level of the other polyclonal isotypes in patients with MM. Immediate skin test response to common environmental allergens was also preserved in patients with MM as compared with normal nonatopic controls. One-year treatment of MM patients with alkylating agents caused a significant decrease in the monoclonal immunoglobulin level and induced a tendency toward decreasing IgE level but had no effect on the polyclonal immunoglobulin concentrations. These findings suggest that IgE production and immediate skin test response is not impaired by the pathologic process in MM patients, in contrast to the production of other polyclonal immunoglobulins. This demonstrates the dissociation between the response of the IgE antibody and the other isotypes. PMID- 8452317 TI - Relationship between dust mite allergen and human IgA in house dust samples. AB - Previous investigators have mentioned that human IgA is found in house dust. IgA has also been reported to be present on human skin and hence in human dander. If human dander is the primary source of food for house dust mites, a relationship would be expected between IgA and dust mite allergen (Der f I) concentrations. We wished to learn whether IgA was consistently detectable in house dust and whether IgA and dust mite allergen concentrations were related. Dust samples were collected from the bedrooms of infants enrolled in a prospective study designed to evaluate the relationship between early allergen exposure and childhood allergic disease. One hundred eighty samples were studied: 50 samples were the initial samples collected from the first 50 infants enrolled, 120 samples were monthly samples obtained from 10 other homes, and 10 additional samples were randomly selected for extraction in a nonprotein containing buffer to determine the percentage of total extractable dust protein contributed by IgA. Finally, nine commercial house dust extracts were studied to learn whether they were similar to the dust samples from study houses. Enzyme linked immunosorbent assays (ELISAs) were used to measure human IgA, human secretory IgA (sIgA) and Der f I concentrations in all of the dust extracts. We found that IgA was consistently present in house dust samples ranging from 3.2 to 2,396 micrograms of IgA per gram of dust. A strong correlation (r = .90) was found between IgA and sIgA concentrations. IgA constituted 0.27% to 6.04% of the total protein in dust samples.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452318 TI - Comparison of powder and aerosolized budesonide in perennial rhinitis: validation of rhinitis quality of life questionnaire. AB - The aims of the study were to compare the efficacy and side effects of intranasal budesonide as a dry powder and as a freon propelled pressurized aerosol in the treatment of perennial rhinitis and to validate a perennial rhinitis quality of life questionnaire. The design was a single-blind, randomized, parallel group comparison of two active treatments over a 6-week period. Sixty adults with symptomatic perennial rhinitis, stratified for atopy, received 400 micrograms intranasal budesonide administered daily either as one inhalation/nostril/day of pure drug powder or two puffs/nostril/day of drug delivered by a freon propelled aerosol. Subjects kept daily symptom diaries and, at each clinic visit, rhinitis quality of life and adverse experiences were recorded. Fifty-eight subjects completed the study. During the 6 weeks, there were significant improvements in symptoms and quality of life in both treatment groups. The improvements tended to be slightly greater in the aerosol group but the differences did not reach significance. Most frequently reported adverse experiences were headache and nosebleed, which were equally distributed in the two groups. We conclude that budesonide taken 400 micrograms daily for 6 weeks was associated with improvements in perennial rhinitis with little evidence of any difference in efficacy or side effects between the powder and aerosol. The questionnaire is a valid instrument for assessing quality of life in perennial rhinitis clinical trials. PMID- 8452319 TI - Episodic angioedema with eosinophilia: a case associated with T cell activation and cytokine production. AB - Episodic angioedema with eosinophilia is a rare syndrome, characterized by periodic attacks of fever, myalgia, angioedema, and oliguria, associated with an increased eosinophil count. The pathogenesis of this disorder is incompletely understood. We describe an additional patient with episodic angioedema and eosinophilia, and review the literature regarding the clinical features and treatment of this disease. Previous hypotheses regarding disease mechanisms are discussed. In our patient, we found high basal levels of interleukin-1 (IL-1) and soluble interleukin-2 receptor (sIL-2R), with further increases in levels of both mediators during attacks. We suggest that IL-1 and T cell activation may play a role in the pathophysiology of episodic angioedema with eosinophilia. PMID- 8452320 TI - Respiratory allergy to the pollen of Mercurialis annua (Euphorbiaceae). AB - We have described ten cases of respiratory allergy to the pollen of Mercurialis annua in the area of Bordighera (Riviera dei Fiori) on the Italian Mediterranean coast. The incidence of sensitivity is only 0.9% in a population of 1081 patients with pollinosis. Since the Euphorbiaceae family (spurges) contains strongly sensitizing allergens (eg, seeds of Ricinus communis and latex of Hevea brasiliensis) our findings raise the possibility that respiratory allergy to the pollens of Mercurialis annua and other spurges has been underestimated throughout the world. PMID- 8452321 TI - Corticosteroid resistance in eosinophilic gastritis--relation to in vitro eosinophil survival and interleukin 5. AB - Eosinophilic gastritis is usually responsive to corticosteroid therapy. In some cases, large doses and protracted treatment are required. This report describes a case of eosinophilic gastritis that was partially corticosteroid resistant. To determine mechanisms that explain this patient's incomplete response to corticosteroid therapy, peripheral blood eosinophils and serum were isolated from the patient. We found the in vitro survival of the patient's eosinophils was prolonged. In addition, his serum both promoted in vitro eosinophil survival and nullified the survival inhibiting of effect of hydrocortisone (10 microM). Furthermore, antibody against interleukin 5 (IL5) partially inhibited the enhanced eosinophil survival produced by the patient's serum and completely blocked the decrease in survival resulting from hydrocortisone. These observations indicate that elevated circulating levels of IL5 may contribute to the peripheral eosinophilia and corticosteroid resistance in some patients with eosinophilic gastritis. PMID- 8452322 TI - Long-term stabilizing effect of angiotensin-converting enzyme inhibition on plasma creatinine and on proteinuria in normotensive type II diabetic patients. AB - OBJECTIVE: To evaluate the long-term effect of angiotensin-converting enzyme inhibition on proteinuria and on the rate of decline in kidney function in patients with type II diabetes mellitus and microalbuminuria. DESIGN: Randomized, double-blind, placebo-controlled trial. Each patient was followed for 5 years. SETTING: Six clinics for diabetes mellitus coordinated by a department of medicine in a university hospital in Israel. PATIENTS: Ninety-four normotensive, type II diabetic patients with microalbuminuria and normal renal function. INTERVENTION: The patients were randomly assigned to receive enalapril, 10 mg per day, or placebo. Any increase in blood pressure was treated with long-acting nifedipine. MEASUREMENTS: Albuminuria, blood pressure, serum creatinine, fasting blood glucose, and glycosylated hemoglobin levels, every 3 to 4 months. RESULTS: In the patients treated with enalapril, albuminuria decreased from 143 +/- 64 (mean +/- SD) mg/24 h to 122 +/- 67 mg/24 h during the first year. Thereafter, we observed a slow increase to 140 +/- 134 mg/24 h after 5 years. In the placebo group, albuminuria increased from 123 +/- 58 mg/24 h to 310 +/- 167 mg/24 h after 5 years. (Difference in rate of change in proteinuria [P < 0.05]). Kidney function (expressed as mean reciprocal creatinine) declined by 13% in the placebo group and remained stable (-1%) in the enalapril group (P < 0.05). Control of blood glucose levels remained stable, in both groups, throughout the study. The mean blood pressure was stable in the enalapril group (initial group mean, 99 +/- 2.1 mm Hg; fifth-year mean, 100 +/- 3.2 mm Hg) and increased in the placebo group from an initial mean value of 97 +/- 3.2 mm Hg to 102 +/- 3.4 mm Hg at the end of the study period (P = 0.082). CONCLUSIONS: In normotensive patients with diabetes mellitus type II, the institution of angiotensin-converting enzyme inhibition during early stages of diabetic nephropathy results in long-term stabilization of plasma creatinine levels and of the degree of urinary loss of albumin. These effects are probably independent of the antihypertensive action of these agents. PMID- 8452323 TI - Ciprofloxacin and loperamide in the treatment of bacillary dysentery. AB - OBJECTIVE: To compare the safety and efficacy of loperamide plus ciprofloxacin with those of ciprofloxacin alone in the treatment of bacillary dysentery. DESIGN: Double-blind, placebo-controlled, randomized clinical trial. SETTING: Hospital in Thailand. PARTICIPANTS: Eighty-eight adults with dysentery seeking medical care between November 1990 and February 1992. Patients who had received prior antibiotics or antimotility drugs were excluded. INTERVENTION: All 88 patients with dysentery were treated with ciprofloxacin, 500 mg twice daily for 3 days. Forty-two of these patients were randomly assigned to receive loperamide, a 4-mg initial dose followed by 2 mg after every loose stool (as many as eight caplets [16 mg] daily), and 46 were randomly assigned to receive placebo. MEASUREMENTS: Stools were collected daily until resolution of diarrhea and again after 10 days. The time to passage of the last unformed stool, number of unformed stools, and symptoms were recorded after treatment. RESULTS: Shigella or enteroinvasive Escherichia coli (53%), Vibrio parahaemolyticus (16%), and Salmonella (7%) were the most common bacterial enteric pathogens identified in 88 patients with dysentery. In patients infected with Shigella or enteroinvasive E. coli, the median duration of diarrhea was 19 hours (25th to 75th percentiles, 6 to 42 hours) for those receiving loperamide plus ciprofloxacin compared with 42 hours (21 to 46 hours) for those receiving ciprofloxacin alone (P = 0.028). The median number of diarrheal stools for those receiving ciprofloxacin and loperamide was 2.0 (1 to 5 stools) compared with 6.5 (2 to 9 stools) for those receiving ciprofloxacin alone (P = 0.016). None of the participants had a temperature greater than 38 degrees C after 24 hours of treatment. None of the patients was infected with the same bacterial enteric pathogen more than 1 day after receiving treatment. CONCLUSIONS: Loperamide decreases the number of unformed stools and shortens the duration of diarrhea in dysentery caused by Shigella in adults treated with ciprofloxacin. PMID- 8452324 TI - Acute mountain sickness in a general tourist population at moderate altitudes. AB - OBJECTIVE: To determine the incidence of acute mountain sickness in a general population of visitors to moderate elevations, the characteristics associated with it, and its effect on physical activity. DESIGN: A cross-sectional study. SETTING: Resort communities located at 6300 to 9700 feet elevation in the Rocky Mountains of Colorado. PARTICIPANTS: Convenience sample of 3158 adult travelers, 16 to 87 years old (mean age [+/- SD], 43.8 +/- 11.8 years). RESULTS: Twenty-five percent of the travelers to moderate elevations developed acute mountain sickness, which occurred in 65% of travelers within the first 12 hours of arrival. Fifty-six percent of those with symptoms reduced their physical activity. The odds favoring acute mountain sickness were 3.5 times as large for visitors whose permanent residence was below 3000 feet elevation as for those whose residence was above 3000 feet; 2.8 times as large for visitors with previous symptoms of acute mountain sickness; and twice as large in travelers younger than 60 years. Women, obese persons, those in poor or average physical condition, and those with underlying lung disease also had a higher occurrence of acute mountain sickness (P < 0.05). CONCLUSIONS: Acute mountain sickness occurs in 25% of visitors to moderate altitudes and affects activity in most symptomatic visitors. Persons who are younger, less physically fit, live at sea level, have a history of acute mountain sickness, or have underlying lung problems more often develop these symptoms. PMID- 8452325 TI - Effect of race on the presentation and management of patients with acute chest pain. AB - OBJECTIVE: To compare racial differences in clinical presentation, natural history, and access to medical care and procedures among emergency-department patients with acute chest pain. DESIGN: Prospective follow-up study of consecutive patients coming to the emergency department because of acute chest pain. SETTING: Two university medical centers. PATIENTS: A total of 3031 patients who were 30 years or older and who came to the emergency department with acute chest pain from 1984 to 1986. MAIN RESULTS: African-Americans tended to have slightly, but not always significantly, lower rates of acute myocardial infarction, acute ischemic heart disease, and major complications, after adjusting for presenting symptoms and signs; the adjusted odds ratios for African Americans were as follows: 0.77 (95% CI, 0.54 to 1.1) for acute myocardial infarction, 0.75 (CI, 0.59 to 0.95) for ischemic heart disease, and 0.79 (CI, 0.45 to 1.4) for death or major complications. Clinical factors classically associated with acute myocardial infarction were equally predictive in African Americans and whites. After adjustments were made for multiple clinical factors, a lower proportion of African-Americans were admitted to the hospital (odds ratio, 0.69; CI, 0.56 to 0.84), and, once admitted, were somewhat less likely to be triaged to the coronary care unit (odds ratio, 0.81; CI, 0.65 to 1.0). In adjusted analyses, African-Americans were as likely to undergo cardiac catheterization as whites (odds ratio, 0.86; CI, 0.64 to 1.2) but were less likely to undergo coronary artery bypass procedures once severity of coronary disease was included in the analysis (odds ratio, 0.24; CI, 0.08 to 0.71). CONCLUSION: African-Americans and whites had a similar presentation and natural history of acute myocardial infarction and, after adjusting for probability of clinical events, similar access to most medical care and cardiac procedures. However, the rate of coronary artery bypass procedures was much lower among African-Americans than among whites. Reasons for this difference should be studied. PMID- 8452326 TI - Early undifferentiated connective tissue disease: III. Outcome and prognostic indicators in early scleroderma (systemic sclerosis). AB - OBJECTIVE: To characterize the course of early scleroderma and to delineate prognostic factors present within 1 year of disease onset that might identify patients at high risk. DESIGN: Inception cohort study. SETTING: Ten university based rheumatology clinics participating in the Cooperative Systematic Studies of Rheumatic Diseases Program. PATIENTS: Forty-eight patients who had had scleroderma for less than 1 year. MEASUREMENTS: Fifteen patients with early scleroderma who died were compared with those still living during the initial study period (1982 to 1992). Kaplan-Meier survival estimation and Cox proportional hazards analysis were used to analyze baseline variables for their ability to predict survival duration. RESULTS: Eight of 15 deaths were due to cardiac or pulmonary system failure. The estimated 5-year survival rate was 68%. Baseline factors that were the most predictive of a poor outcome included the presence of abnormal cardiopulmonary signs and abnormal urine sediment (pyuria, hematuria). CONCLUSION: Evidence of early cardiopulmonary disease, renal disease, inflammation, or immune activation may identify a subset of patients with scleroderma who will experience rapidly progressive disease and early death. PMID- 8452327 TI - Symptomatic exacerbation of Crohn disease after treatment with high-dose interleukin-2. PMID- 8452328 TI - Measuring health-related quality of life. AB - Clinicians and policymakers are recognizing the importance of measuring health related quality of life (HRQL) to inform patient management and policy decisions. Self- or interviewer-administered questionnaires can be used to measure cross sectional differences in quality of life between patients at a point in time (discriminative instruments) or longitudinal changes in HRQL within patients during a period of time (evaluative instruments). Both discriminative and evaluative instruments must be valid (really measuring what they are supposed to measure) and have a high ratio of signal to noise (reliability and responsiveness, respectively). Reliable discriminative instruments are able to reproducibly differentiate between persons. Responsive evaluative measures are able to detect important changes in HRQL during a period of time, even if those changes are small. Health-related quality of life measures should also be interpretable--that is, clinicians and policymakers must be able to identify differences in scores that correspond to trivial, small, moderate, and large differences. Two basic approaches to quality-of-life measurement are available: generic instruments that provide a summary of HRQL; and specific instruments that focus on problems associated with single disease states, patient groups, or areas of function. Generic instruments include health profiles and instruments that generate health utilities. The approaches are not mutually exclusive. Each approach has its strengths and weaknesses and may be suitable for different circumstances. Investigations in HRQL have led to instruments suitable for detecting minimally important effects in clinical trials, for measuring the health of populations, and for providing information for policy decisions. PMID- 8452329 TI - Chemotherapeutic failure: resistance or insensitivity? AB - Immunocyte and germ cell neoplasms, often curable by chemotherapy, arise from normal tissues most vulnerable to the effects of cytotoxic drugs; generalizing from these results to treating other tumors with such agents may not be entirely valid. Our limited success in treating epithelial neoplasms may be due to insensitivity rather than to drug resistance. Well-designed attempts to overcome resistance have been unsuccessful. The acquired immunodeficiency syndrome has not confirmed the putative role of immune surveillance in the pathogenesis of most neoplasms. The limited success of the most elaborate immunotherapies suggests that they, too, are nonspecific cell-killing techniques. Immunologic and cytotoxic drug therapies deserve further investigation but on a smaller scale. Neoplastic cell molecular biology, unknown when these therapies were developed, is being rapidly elucidated and may make it possible to treat malignancies by modulating cell physiology. Success of therapies based on the advances, in molecular biology, is not more uncertain than that of traditional treatments. Differentiation-induction techniques have already induced remissions in patients with acute promyelocytic leukemia and squamous cell carcinomas. PMID- 8452330 TI - Biological basis for cancer treatment. AB - The new knowledge of the regulation of cell growth and the genetic and biochemical changes that lead to malignancy have created many new opportunities for cancer drug discovery. These new targets include oncogenes, growth factors and their receptors, signal transduction pathways, and cell differentiation signals. Attempts to identify new therapies based on these targets can complement traditional drug discovery efforts that rely on high-volume screening of candidate natural products and synthetic chemicals against human tumor cell lines and against defined molecular reactions. Through modern computer-based data analysis, drug screening data can be used to establish mechanism of drug action of new agents; these analyses shed light on patterns of cross-resistance of new compounds and their interactions with defined molecular targets as well as allow selection of chemically and biologically unique agents as candidates for clinical development. PMID- 8452331 TI - Sir William Osler's philosophy on death. PMID- 8452333 TI - Who's responsible? PMID- 8452332 TI - Angiotensin-converting enzyme inhibitors and progression of diabetic nephropathy. PMID- 8452334 TI - Conflict of interest. International Committee of Medical Journal Editors. PMID- 8452335 TI - Searching for patent foramen ovale in patients with stroke. PMID- 8452336 TI - Hiccups, compulsive water drinking, and hyponatremia. PMID- 8452337 TI - Polypharmacy in skilled-nursing facilities. PMID- 8452338 TI - Polypharmacy in skilled-nursing facilities. PMID- 8452339 TI - Osteopathy, chiropractic, and spinal manipulation. PMID- 8452340 TI - Osteopathy, chiropractic, and spinal manipulation. PMID- 8452341 TI - Osteopathy, chiropractic, and spinal manipulation. PMID- 8452342 TI - Freebies: is the enemy us? PMID- 8452343 TI - Molecular basis of beta-lactamase induction in bacteria. PMID- 8452344 TI - Efficacy of cefuroxime axetil suspension compared with that of penicillin V suspension in children with group A streptococcal pharyngitis. AB - The bacteriological and clinical efficacies of cefuroxime axetil suspension (20 mg/kg of body weight per day in two divided doses) were compared with those of penicillin V suspension (50 mg/kg/day in three divided doses) in a multicenter, randomized, evaluator-blinded study. Children aged 2 to 13 years with clinical signs and symptoms of acute pharyngitis and a positive throat culture for group A beta-hemolytic streptococci (GABHS) were eligible. Patients were assessed and samples from the throat for culture were obtained at the time of diagnosis, 3 to 7 days after the initiation of treatment, and 4 to 8 days and 19 to 25 days after the completion of 10 days of therapy. Of the 385 evaluable patients, GABHS were eradicated from 244 of 259 (94.2%) cefuroxime-treated patients and 106 of 126 (84.1%) penicillin-treated patients (P = 0.001). Complete resolution of the signs and symptoms present at the time of diagnosis was achieved in 238 of 259 (91.9%) cefuroxime-treated patients and 102 of 126 (81.0%) penicillin-treated patients (P = 0.001). Potential drug-related adverse events were reported in 7.0 and 3.2% of the cefuroxime- and penicillin-treated patients, respectively (P = 0.078). In the present study, cefuroxime axetil suspension given twice daily resulted in significantly greater bacteriological and clinical efficacies than those of penicillin V suspension given three times daily to pediatric patients with acute pharyngitis and a positive throat culture for GABHS. PMID- 8452345 TI - Pharmacokinetics of nevirapine: initial single-rising-dose study in humans. AB - Nevirapine, a nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV 1) reverse transcriptase, was administered for the first time to humans in a pilot study designed to investigate the pharmacokinetics and tolerance of the drug following single-dose administration to 21 HIV-1-infected individuals. The study followed a parallel design. Different groups of three subjects each were given one of seven dose levels (2.5 to 400 mg) in sequential order, starting with the lowest dose. Each subject received only one dose. Nevirapine was rapidly absorbed at all doses from a tablet formulation. Peak concentrations in plasma were generally achieved within 90 min of dose administration. Secondary peaks were also noted between 3 and 12 h or between 24 and 28 h, the latter being noted mainly in subjects receiving the higher doses. After 24 h, concentrations in plasma declined in a log-linear fashion. The terminal half-life and mean residence time exceeded 24 h in all but one subject, indicating a prolonged disposition time in this population. Both peak concentrations in plasma and areas under the plasma concentration-time curves increased proportionally with increasing dose from 2.5 to 200 mg; however, the increase in the peak concentration in plasma and the area under the plasma concentration-time curve appeared to be less than proportional at the 400-mg dose level in this small number of subjects. This observation may be due to increased clearance or decreased absorption at the highest dose or population differences in absorption or clearance between doses. Studies with a cross-over design are planned to resolve these issues. The pharmacokinetic characteristics of nevirapine are appropriate for once-daily administration. A daily 12.5-mg dose is predicted to achieve trough concentrations in plasma in the range required to totally inhibit replication of wild-type HIV-1 in human T-cell culture. PMID- 8452346 TI - In vitro and in vivo activities of the nitroimidazole CGI 17341 against Mycobacterium tuberculosis. AB - CGI 17341 (2-ethyl-5-nitro-2,3-dihydro[2-1b]imidazo-oxazole) is a novel orally active representative of the 5-nitroimidazole series of antimicrobial agents. At concentrations ranging from 0.1 to 0.3 micrograms/ml, CGI 17341 inhibited the drug-susceptible and multi-drug-resistant strains of Mycobacterium tuberculosis. CGI 17341 had no cross-resistance with isoniazid, rifampin, streptomycin, or ethambutol. While the in vitro activity of CGI 17341 against M. tuberculosis was comparable to those of isoniazid and rifampin, it was superior to those of streptomycin, ciprofloxacin or norfloxacin, and oxazolidinone DuP 721. The MIC of CGI 17341 was not affected when the pH of the medium was decreased from 6.8 to 5.6, while four- to sixfold increases in the MICs of ciprofloxacin and isoniazid were observed. In mice infected with M. tuberculosis, the 50% effective dose for CGI 17341 was 7.7 mg/kg of body weight (95% confidence limits, 3.5 and 10.27) when administered on days 11 and 12 postinfection. CGI 17341 gave a dose dependent (r = 0.995) and significant increase in the survival time. Our data indicate that the 5-nitroimidazole CGI 17341 is a promising and novel antituberculosis compound with potent in vitro and in vivo activities. Further investigations on this compound are warranted. PMID- 8452347 TI - Uptake and intracellular activity of fluconazole in human polymorphonuclear leukocytes. AB - The penetration of fluconazole into human polymorphonuclear leukocytes (PMNs) and tissue culture epithelial cells (McCoy) was evaluated. At different extracellular concentrations (0.5 to 10 mg/liter), fluconazole reached cell-associated concentrations greater than the extracellular ones in either human PMNs (intracellular concentration to extracellular concentration ratio, > or = 2.2) or McCoy cells (intracellular concentration to extracellular concentration ratio, > or = 1.3). The uptake of fluconazole by PMNs was rapid and reversible but was not energy dependent. The intracellular penetration of fluconazole was not affected by environmental pH or temperature. Ingestion of opsonized zymosan and opsonized Candida albicans did not significantly increase the amount of PMN-associated fluconazole. At therapeutic extracellular concentrations, the intracellular activity of fluconazole against C. albicans in PMNs was significantly lower than that of amphotericin B. It was concluded that fluconazole reaches high intracellular concentrations within PMNs but shows moderate activity against intracellular C. albicans in vitro. PMID- 8452348 TI - Expression of the tetK gene from Staphylococcus aureus in Escherichia coli: comparison of substrate specificities of TetA(B), TetA(C), and TetK efflux proteins. AB - The tetK gene, which encodes a tetracycline efflux pump from Staphylococcus aureus, was expressed in Escherichia coli by using an inducible, low-level expression system. The tetK gene, as well as the tetA(B) gene from the transposon Tn10 and the tetA(C) gene from plasmid pBR322, was subjected to the regulatory control of the lac repressor, and resistance to tetracycline was measured as a function of the isopropyl-beta-D-thiogalactopyranoside concentration. The maximum resistance of the E. coli strain containing the tetK construct was comparable to the maximum resistance of the strain containing the tetA(C) construct but was less than the resistance of the strain containing the tetA(B) construct. Overexpression of the tetK, tetA(B), or tetA(C) genes was toxic. When expression was regulated so that resistance to tetracycline was comparable, then the TetA(B) and TetA(C) proteins conferred very similar levels of resistance to a variety of tetracycline derivatives. In contrast, the TetK protein was less capable of conferring resistance to the tetracycline derivatives minocycline, 6-deoxy-6 demethyltetracycline, and doxycycline. The implications for the recognition of various tetracycline substituents by the TetK protein are discussed. PMID- 8452349 TI - beta-Lactamase-mediated inactivation and efficacy of cefazolin and cefmetazole in Staphylococcus aureus abscesses. AB - 12694668 Clinical reports and animal models have demonstrated that cefazolin may have decreased efficacy against some strains of Staphylococcus aureus because of type A beta-lactamase-mediated hydrolysis. We sought to measure biologically active cefazolin concentrations within abscesses with high concentrations of S. aureus and compare the concentrations with those of cefmetazole, a beta-lactamase stable cephamycin. A type A beta-lactamase-producing strain of S. aureus with a demonstrated inoculum effect against cefazolin (MIC at an inoculum of 5 x 10(5) CFU/ml, 1.0 micrograms/ml; MIC at an inoculum of 5 x 10(7) CFU/ml, 32.0 micrograms/ml) but not cefmetazole (MICs at inocula of 5 x 10(5) and 5 x 10(7) CFU/ml, 2.0 micrograms/ml) was used. Cefazolin or cefmetazole (100 mg/kg of body weight every 8 h for 8 days) was administered to rabbits with infected tissue cages. No differences in the concentrations of the two drugs in the uninfected tissue cages were observed. Higher concentrations of cefmetazole than cefazolin were found in infected tissue cages at day 3 (5.9 +/- 0.7 versus 2.2 +/- 0.3 micrograms/ml; P < 0.01), day 5 (9.1 +/- 2.6 versus 3.6 +/- 0.7 micrograms/ml; P = 0.02), and day 8 (9.4 +/- 1.4 versus 4.8 +/- 0.9 micrograms/ml; P = 0.01) after infection. Cefazolin and cefmetazole were equally effective in reducing the bacterial concentration in the abscess. In vitro experiments demonstrated greater cefazolin than cefmetazole degradation by S. aureus, but the differences were greater in serum than in abscess fluid supernatants. We conclude that abscess cefazolin concentrations are diminished by type A beta-lactamase-producing S. aureus, but this did not affect drug efficacy in this model. PMID- 8452350 TI - Synergistic activity of ceftriaxone combined with netilmicin administered once daily for treatment of experimental streptococcal endocarditis. AB - We have conducted experiments to determine if one daily injection of netilmicin (NET) would be synergistic with the broad-spectrum cephalosporin ceftriaxone (CRO) in the treatment of experimentally induced endocarditis. Rats with catheter induced aortic vegetations were infected intravenously with 3 x 10(7) CFU of a beta-lactam-sensitive strain of Streptococcus sanguis or a beta-lactam-resistant strain of Streptococcus mitis. Treatment with the antibiotics alone (CRO, 10 mg/kg of body weight every 8 h; NET, 18 mg/kg every 24 h) or in combinations which had proved synergistic in in vitro time-kill curves was commenced 48 h postinfection and continued for 72 h. The results show that the combination was markedly effective against S. sanguis and moderately effective against S. mitis, while, with the protocol used here, the agents alone were not. The results suggest that CRO-NET should be an effective combination for treating streptococcal endocarditis in humans and may permit a shorter duration of treatment and once-a-day dosing to be used. PMID- 8452351 TI - Activity of quinolones in the Ames Salmonella TA102 mutagenicity test and other bacterial genotoxicity assays. AB - Eight quinolones were examined for their bacterial mutagenicity in the Ames Salmonella TA102 assay and for their effects in other bacterial genotoxicity assays. In the quantitative Ames plate incorporation assay, all eight quinolones induced His+ deletion reversion in Salmonella tester strain TA102, with maximum reversion observed at about two to eight times the MIC. The quinolones also induced the SOS response. At quinolone concentrations close to the MIC, SOS cell filamentation gene sulA was induced in sulA::lacZ fusion strain Escherichia coli PQ37. RecA-mediated cleavage of lambda repressor in lambda::lacZ fusion strain E. coli BR513 was measurable at about 10 times the MIC, though no induction occurred at 20 micrograms of nalidixic or oxolinic acid per ml. Genotoxicity of quinolones also was observed in the Bacillus subtilis DNA repair assay, in which the mutant strain M45 (recA) was more susceptible to quinolones than its parent strain, H17 (rec+). The results from these analyses indicate that quinolones induce SOS functions and are mutagenic in bacteria; these properties correspond to their antimicrobial activities. PMID- 8452352 TI - Pharmacokinetics of meropenem in patients with various degrees of renal function, including patients with end-stage renal disease. AB - The pharmacokinetics of meropenem were studied after intravenous infusion in 13 patients grouped according to the impairment of their renal function. Creatinine clearance (CLCR) was greater than 50, 50 to 30, and less than 30 ml/min in groups I, II, and III, respectively. Two other groups, groups IV and V, each comprising four patients with end-stage renal disease (CLCR, < 5 ml/min), were also studied, the former on days off of hemodialysis and the latter on days of hemodialysis. The elimination half-lives of meropenem were 1.54 +/- 0.70 h in group I patients, 3.36 +/- 1.02 h in group II patients, and 5.00 +/- 1.05 h in group III patients. Cumulative urinary excretion accounted for 48.5% of the dose in group I patients and decreased progressively with a decline in renal function. Hemodialysis shortened the elimination half-life of meropenem from 7.0 h to 2.9 h. H-4295, the main metabolite of meropenem, had a peak level in plasma of 0.5 to 1.0 h in patients with renal failure. The level of H-4295 decreased with hemodialysis. The dosing interval of meropenem should be prolonged in a regular proportion to the decline in CLCR (12 h in group II patients and 24 h in group III patients). In patients receiving hemodialysis, dosing after each hemodialysis session is recommended. PMID- 8452353 TI - Evaluation of the efficacy of ciprofloxacin against Streptococcus pneumoniae by using a mouse protection model. AB - A mouse protection model was used to investigate the association of the pharmacokinetics and pharmacodynamics with the in vivo efficacy of ciprofloxacin compared with that of penicillin G in the treatment of mice infected with Streptococcus pneumoniae ATCC 6303. Mice were inoculated intraperitoneally with 10 times the minimum lethal dose of S. pneumoniae. For determination of the 50% protective dose, subcutaneous antibiotics were begun 1 h after infection and were continued for 24 h. The 50% protective doses of ciprofloxacin and penicillin G were 25.52 +/- 1.95 and 0.307 +/- 0.006 mg/kg of body weight, respectively, an 83 fold difference in efficacy. For 100% protection with penicillin G, the time that the drug concentration needed to remain above the MIC was 51 min, a value easily achieved in most clinical situations. For 100% protection with ciprofloxacin, the peak concentration/MIC ratio must reach a value of 10.6. This ratio is rarely achieved with this drug against S. pneumoniae in clinical practice. These pharmacodynamic differences probably contribute to the reported differences in clinical success between these agents. PMID- 8452354 TI - Roles of liposome composition and temperature in distribution of amphotericin B in serum lipoproteins. AB - The role of liposome composition and temperature in the distribution of amphotericin B (AmB) with serum lipoproteins and the role of particle charge in AmB transfer to serum lipoproteins were determined. Serum obtained from healthy volunteers was incubated with known concentrations of AmB or different liposomal formulations of AmB (1 to 100 micrograms/ml) at 37 degrees C for various time intervals (5, 10, 20, 30, 45, and 60 min). After each interval, serum was removed and separated into high-density lipoprotein (HDL) and low-density lipoprotein (LDL) fractions by an LDL-direct assay. The distribution of AmB (Fungizone) at 5 min through 1 h of incubation at 25 degrees C remained constant and was similar in the HDL and LDL fractions. At 37 degrees C, at 5 through 45 min of incubation, 54 to 61% of AmB was recovered in the HDL fraction; however, at 1 h more than 75% of the AmB concentration was recovered in the HDL fraction. In contrast, 87.5 to 92% AmB was recovered in the HDL fraction throughout the incubation when negatively charged liposomal AmB (dimyristoylphosphatidylcholine [DMPC]:dimyristoylphosphatidylglycerol [DMPG], 7:3 [wt/wt]) was used. With positively charged liposomes, 75 to 87.7% of AmB was recovered in the HDL fraction through the different time points studied. AmB incorporated into DMPC (neutral) and DMPG (negative) liposomes, and AmB was distributed in an HDL:LDL ratio of 6:4 following 1 h of incubation. Ninety percent of AmB and 80% of the lipid were found in the HDL fraction in a 3:1 molar DMPG:AmB ratio and in the LDL fraction in a 6:1 molar ratio. Lipid charge and temperature play a role in AmB distribution into serum lipoproteins. AmB and DMPG may contransfer as an intact drug-lipid complex to serum lipoproteins. PMID- 8452355 TI - Use of a predictor panel to evaluate susceptibility testing methods for ampicillin-sulbactam. AB - A predictor panel of clinical isolates that produce a variety of types and amounts of beta-lactamases was used to assess the accuracies of a variety of susceptibility tests for ampicillin-sulbactam. Combinations of ampicillin sulbactam in ratios of 1:1 and 2:1 and with sulbactam held constant at concentrations of 4 and 8 micrograms/ml were examined in dilution tests performed in agar and broth. In addition, disks containing 10/10, 20/10, 20/20, and 20/30 micrograms of ampicillin-sulbactam were examined in diffusion tests. The results indicated that the MICs obtained in broth microdilution tests performed with each of the four combinations differed, on average, less than twofold. Of the disks tested, the 20/10-micrograms ampicillin-sulbactam disk provided the best separation between susceptible and resistant strains when interpretive criteria for resistance was a zone size of < or = 16 mm and that for susceptibility was a zone size of > or = 21 mm. This disk also gave the highest overall agreement with MICs, regardless of the combination used in the broth microdilution test. Discrepancies between agar and broth microdilution MICs were greater than twofold, on average, and this necessitated recommendation of separate criteria for the two methods. Thus, a predictor panel was very useful in identifying the parameters of susceptibility tests that were most accurate in identifying strains that were susceptible and resistant to ampicillin-sulbactam. PMID- 8452356 TI - Decimal assay for additivity of drugs permits delineation of synergy and antagonism. AB - Although there are many in vitro tests for drug interactions, few possess a linear, predictable dose-dependent end point or have a precise definition for additivity. Therefore, a new test with both of these features, the decimal assay for additivity, was developed. This test is based on a disk diffusion assay and the strict linear relationship between drug mass and size of the inhibition zone. When the decimal assay for additivity was applied to combinations known on a mechanistic basis to be additive, synergistic, or antagonistic, results of the new test always reflected the expected drug interaction. For example, synergy between trimethoprim and sulfamethoxazole was detected in tests with Escherichia coli and Haemophilus influenzae, as was antagonism between cefoxitin and cefotaxime in tests with Enterobacter cloacae. Quinolones plus chloramphenicol appeared to be antagonistic. In addition to correctly identifying the drug interaction, the decimal assay for additivity identified the drug ratio producing the maximal drug interaction. These results suggest that the decimal assay for additivity should prove very useful in future studies of drug interactions. PMID- 8452357 TI - Cytochrome P-450 complex formation by dirithromycin and other macrolides in rat and human livers. AB - Some macrolide antibiotics cause clinical drug interactions, resulting in altered metabolism of concomitantly administered drugs, via formation of an inactive cytochrome P-450 complex. In the present study, the formation of a cytochrome P 450 type I binding spectrum and a metabolic intermediate complex by troleandomycin and dirithromycin was assessed in liver microsomes obtained from untreated rats and phenobarbital- or dexamethasone-pretreated rats. Troleandomycin produced a type I binding spectrum and metabolic intermediate complex in microsomes from dexamethasone- and phenobarbital-pretreated rats. Dirithromycin did not produce a detectable type I binding spectrum but formed a small cytochrome P-450 metabolic intermediate complex (6% of that formed by troleandomycin) in microsomes from dexamethasone-pretreated rats only. The formation of a cytochrome P-450 type I binding spectrum and a metabolic intermediate complex by troleandomycin, erythromycin, dirithromycin, and erythromycylamine was also assessed in microsomes prepared from human livers. Troleandomycin and erythromycin formed a type I binding spectrum and a metabolic intermediate complex which were larger in microsomes from subjects on barbiturate therapy than in microsomes from subjects with no recent barbiturate exposure. Erythromycylamine did not form a detectable type I binding spectrum with any of the human microsomal samples, but a small metabolic intermediate complex was formed with microsomes from a subject on phenobarbital, phenytoin, and propranolol therapy. Dirithromycin did not form a detectable type I binding spectrum or a metabolic intermediate complex in any human liver sample. Preclinical quantitation of the human metabolic intermediate complex may be helpful in predicting the possibility of clinical drug interactions of new drug candidates. PMID- 8452358 TI - Effects of interleukin-8 on nonspecific resistance to infection in neutropenic and normal mice. AB - The effect of treatment with interleukin-8 (IL-8), a neutrophil-activating cytokine, was investigated in normal and neutropenic mice infected with a lethal dose of Pseudomonas aeruginosa, Klebsiella pneumoniae, or Plasmodium berghei. Intraperitoneal (i.p.) IL-8 treatment was associated with accelerated death when IL-8 was administered shortly before i.p. infection with P. aeruginosa or shortly after i.p. infection with P. aeruginosa and K. pneumoniae. Histopathological analyses demonstrated a tendency to more severe organ lesions in IL-8-treated mice. Only nonneutropenic mice that received IL-8 shortly before the infectious challenge and at the site of infection were protected by IL-8. Whether IL-8 is protective of or detrimental to the survival of infection appeared to depend on the presence of bacteria at the injection site and on the presence of neutropenia. IL-8 may be an important participant in the cascade of interacting cytokines that is induced by the lethal infectious challenge. PMID- 8452359 TI - Analysis of vancomycin entry into pulmonary lining fluid by bronchoalveolar lavage in critically ill patients. AB - Vancomycin penetration into the fluid lining the epithelial surface of the lower respiratory tract was studied by performing fiberoptic bronchoscopy with bronchoalveolar lavage on 14 critically ill, ventilated patients who had received the drug for at least 5 days. The apparent volume of epithelial lining fluid (ELF) recovered by bronchoalveolar lavage was determined by using urea as an endogenous marker. Vancomycin levels in ELF ranged from 0.4 to 8.1 micrograms/ml (mean, 4.5 micrograms/ml), while the mean simultaneous level of the drug in plasma was 24 micrograms/ml (range, 9 to 37.4 micrograms/ml). There was a significant relationship (r = 0.64, P < 0.02) between vancomycin levels in plasma and those in ELF, with a correlation whose slope (0.15) indicated that the blood to-ELF ratio of drug penetration was 6:1. Using the albumin concentration in ELF as a marker of lung inflammation, we found that vancomycin penetration was higher in patients with ELF albumin values of > or = 3.4 mg/ml than in patients with normal values (< 3.4 mg/ml) (P < 0.02). These results suggest that the vancomycin distribution includes the ELF of the lower respiratory tract at a concentration that is dependent upon the levels in blood and the alveolar capillary membrane protein permeability. These concentrations were well above the MICs for most staphylococci and enterococci. PMID- 8452360 TI - Penetration of fleroxacin into breast milk and pharmacokinetics in lactating women. AB - Fleroxacin was administered to seven lactating women as a single oral dose of 400 mg. Plasma, urine, and milk samples were collected for up to 48 h after administration. Drug concentrations were determined by a reversed-phase high pressure liquid chromatography method and were used for the pharmacokinetic evaluation. At approximately 2 h after oral administration, a maximum concentration of 5.6 mg/liter was determined in plasma; the area under the plasma concentration-time curve (AUC) amounted to 70.3 mg.h/liter, and the elimination half-life in the postdistributive phase was 8 h. Total systemic clearance was 97.3 ml/min, and urinary excretion was 38% of the dose within 48 h. In addition, 8.6% of the N-demethyl metabolite and 4.4% of the N-oxide metabolite were recovered from urine. In comparison with previous results obtained with healthy male volunteers, the time to reach maximum concentrations in plasma was twice as long in the nursing women, and total clearance as well as urinary elimination were reduced by 25%. In breast milk, the mean maximum concentration was 3.5 mg/liter, which was reached 2.6 h after drug administration. The elimination half life of fleroxacin in milk was identical to that in plasma, and the AUC reached 43.3 mg.h/liter. On the basis of the comparison of the AUC in milk versus the AUC in plasma, the proportion of fleroxacin penetration into milk was 62%. The cumulative excretion in milk amounted to only 0.219 mg within 48 h. On the basis of an average daily intake of milk of a breast-fed child of 150 ml/kg of body weight, the maximum daily ingested fleroxacin dose would not exceed 10 mg. However, quinolones are known to induce arthropathy in juvenile animals, and therefore, administration of fleroxacin to breast-feeding women cannot be allowed. PMID- 8452361 TI - In vitro and in vivo antibacterial activities of FK037, a novel parenteral broad spectrum cephalosporin. AB - FK037, a new parenteral cephalosporin, is an oxime-type cephem antibiotic with a 1-hydroxyethyl-5-amino-pyrazole moiety at the 3 position. FK037 was evaluated for antimicrobial activity in vitro and in vivo. In vitro, FK037 was twofold or more active than ceftazidime, cefoperazone, cefotaxime, and ceftriaxone against Pseudomonas aeruginosa (MIC for 90% of the strains [MIC90] = 32 micrograms/ml), members of the family Enterobacteriaceae (MIC90 < or = 2 micrograms/ml), group A streptococci (MIC90 = 0.015 microgram/ml), and methicillin-sensitive or resistant coagulase-negative staphylococci (MIC90 = 2 and 16 micrograms/ml, respectively). In addition, the activity of FK037 was equal to or greater than that of ceftazidime, cefotaxime, or ceftriaxone against Streptococcus pneumoniae (MIC90 = 0.12 microgram/ml) and methicillin-sensitive or -resistant Staphylococcus aureus (MIC90 = 2 and 16 micrograms/ml, respectively). FK037 was more active in vitro than cefepime (two- to fourfold) and cefpirome (twofold) against S. aureus. In murine systemic infection models, FK037 showed potent activity against P. aeruginosa, Escherichia coli, and methicillin-sensitive and methicillin-resistant S. aureus. FK037 was also efficacious in a mouse model of pyelonephritis caused by S. aureus or Klebsiella pneumoniae and in a mouse model of pneumococcal pneumonia caused by S. pneumoniae. Additional studies on this compound to assess its potential clinical utility are warranted. PMID- 8452362 TI - Efficacy of ceftazidime and aztreonam alone or in combination with amikacin in experimental left-sided Pseudomonas aeruginosa endocarditis. AB - The in vivo efficacies of ceftazidime, aztreonam, and the combinations of ceftazidime with amikacin and aztreonam with amikacin were studied in the rabbit left-sided endocarditis model by using two strains of Pseudomonas aeruginosa, one multisusceptible and one multiresistant, in a total of 156 animals. Antibiotics were given intramuscularly for 10 days, as follows: amikacin, 7 mg/kg of body weight every 8 h, and ceftazidime and aztreonam, 50 mg/kg every 8 h. All regimens except amikacin alone significantly reduced the number of CFU per gram of vegetation (P < or = 0.008), but only for the multisusceptible strain for which sterile vegetations were obtained in 20, 25, 21, 75, and 53% of the groups treated with amikacin, ceftazidime, aztreonam, and the combination groups ceftazidime-amikacin and aztreonam-amikacin, respectively (ceftazidime plus amikacin versus controls, P = 0.001). Regarding the decrease in the numbers of colonies in vegetations, (i) all regimens significantly reduced the number of CFU per gram of vegetation (P < 0.001), (ii) results with ceftazidime-amikacin compared with those with monotherapy were significantly different (P < or = 0.007), and (iii) results with aztreonam-amikacin, although better than those with monotherapy, were marginally not statistically significant. At 1 h postdose, mean amikacin, aztreonam, and ceftazidime levels in serum were 35 +/- 19.4, 89.6 +/- 8.16, and 92.61 +/- 11.52 micrograms/ml, respectively. It was concluded that the combination of ceftazidime, and possibly aztreonam, with amikacin given at high doses and short intervals could have a place in the therapy of patients with left-sided endocarditis caused by P. aeruginosa. PMID- 8452363 TI - Susceptibilities of Mycoplasma bovis, Mycoplasma dispar, and Ureaplasma diversum strains to antimicrobial agents in vitro. AB - The purpose of this study was to determine the susceptibility of various strains of Mycoplasma bovis, Mycoplasma dispar, and Ureaplasma diversum, which are prevalent causes of pneumonia in calves, to 16 antimicrobial agents in vitro. The MICs of the antimicrobial agents were determined by a serial broth dilution method for 16 field strains and the type strain of M. bovis, for 19 field strains and the type strain of M. dispar, and for 17 field strains of U. diversum. Final MICs for M. bovis and M. dispar were read after 7 days and final MICs for U. diversum after 1 to 2 days. All strains tested were susceptible to tylosin, kitasamycin, and tiamulin but were resistant to nifuroquine and streptomycin. Most strains of U. diversum were intermediately susceptible to oxytetracycline but fully susceptible to chlortetracycline; most strains of M. bovis and M. dispar, however, were resistant to both agents. Strains of M. dispar and U. diversum were susceptible to doxycycline and minocycline, but strains of M. bovis were only intermediately susceptible. Susceptibility or resistance to chloramphenicol, spiramycin, spectinomycin, lincomycin, or enrofloxacin depended on the species but was not equal for the three species. The type strains of M. bovis and M. dispar were more susceptible to various antimicrobial agents, including tetracyclines, than the field strains. This finding might indicate that M. bovis and M. dispar strains are becoming resistant to these agents. Antimicrobial agents that are effective in vitro against all three mycoplasma species can be considered for treating mycoplasma infections in pneumonic calves. Therefore, tylosin, kitasamycin, and tiamulin may be preferred over oxytetracycline and chlortetracycline. PMID- 8452364 TI - Activity of the carbapenem panipenem and role of the OprD (D2) protein in its diffusion through the Pseudomonas aeruginosa outer membrane. AB - Evidence of permeation of panipenem through the OprD (D2) channel of Pseudomonas aeruginosa outer membrane was shown by using OprD protein-producing and nonproducing strains which contained plasmid pHN4, which codes for L-1 beta lactamase of Xanthomonas maltophilia. Permeation by panipenem was determined by measuring hydrolysis of the carbapenem by beta-lactamase in the periplasmic space. Permeation by panipenem was also determined by counting uptake of [14C]panipenem into P. aeruginosa PAO1 and its OprD protein-deficient mutant, and this permeation of PAO1 was inhibited by L-lysine. These results indicate that panipenem, as well as imipenem, uses the OprD channel, which functions as a specific channel for diffusion of basic amino acids. Panipenem and imipenem showed stronger activities against PAO1 and clinical isolates in human serum than in Mueller-Hinton broth, which contains more amino acids than human serum does. The activities of the carbapenems were reduced by addition of L-lysine to human serum. Similar results were obtained with mouse serum and ascitic fluid. In contrast, such a change in the activities of carbapenems was not observed with an OprD protein-deficient mutant, suggesting that the main reason for the strong activities of carbapenems in biological fluids is a decrease in competition between the antibiotics and basic amino acids for permeation through the OprD channel. Panipenem and imipenem showed much stronger therapeutic efficacies against experimental infections with P. aeruginosa in mice than did the reference antibiotics. Their in vivo activities were more consistent with their MICs in biological fluids than with those in Mueller-Hinton broth. PMID- 8452365 TI - Activities of several benzimidazoles and tubulin inhibitors against Giardia spp. in vitro. AB - Previous studies in our laboratory have shown that albendazole is effective against Giardia spp. in vitro and in vivo, prompting an investigation of the effects of several related benzimidazoles (BZs) on the viability of this protozoan parasite. A range of BZs was tested, and their effects were compared with those of a number of microtubule inhibitors. The effects produced by the two types of drugs were markedly similar, namely, trophozoite detachment and distortion of morphology and general structure, indicating a potential antimicrotubule mode of action for BZs. Mebendazole, albendazole, and fenbendazole proved to be among the most effective BZs tested, exhibiting apparent irreversibility. Nocodazole, oxfendazole, and albendazole sulfoxide, among others, produced transient inhibitions only. Further studies are required to evaluate all available BZs and other antigiardial agents to ensure the development of the most effective and safest antigiardial agent possible. PMID- 8452366 TI - Differential antiherpesvirus and antiretrovirus effects of the (S) and (R) enantiomers of acyclic nucleoside phosphonates: potent and selective in vitro and in vivo antiretrovirus activities of (R)-9-(2-phosphonomethoxypropyl)-2,6 diaminopurine. AB - The (S)- and (R)-enantiomers of acyclic purine nucleoside phosphonate analogs (i.e., 3-hydroxy-2-phosphonomethoxypropyl [HPMP] derivatives, 3-fluoro-2 phosphonomethoxypropyl [FPMP] derivatives, and 2-phosphonomethoxypropyl [PMP] derivatives of adenine [A], 2-aminopurine, 2,6-diaminopurine [DAP], and guanine [G]) have been synthesized and evaluated for antiviral activity. As a rule, the HPMP derivatives proved effective against DNA viruses but not RNA viruses or retroviruses. In particular, (S)-HPMPA, (S)-HPMPDAP, and (R)- and (S)-HPMPG were exquisitely inhibitory to herpes simplex virus type 1 (50% effective concentrations, 0.63, 0.22, 0.10, and 0.66 microM, respectively). The FPMP and PMP derivatives showed marked inhibitory activities against retroviruses but not DNA viruses. The (S)-enantiomer of FPMPA and the (R)-enantiomer of PMPA were approximately 30- to 100-fold more effective against human immunodeficiency virus and Moloney murine sarcoma virus (MSV) than their enantiomeric counterparts. In contrast, both (S)- and (R)-enantiomers of the DAP and G derivatives proved equally effective against retroviruses, except for (R)-PMPDAP, which was 15- to 40-fold more inhibitory than (S)-PMPDAP. (R)-PMPDAP emerged as the most potent and selective inhibitor of MSV-induced transformation of murine C3H/3T3 cells and human immunodeficiency virus-induced cytopathicity in MT-4 and CEM cells (50% effective concentration, approximately 0.1 to 0.6 microM). When administered intraperitoneally at a single dose as low as 2 mg/kg, (R)-PMPDAP efficiently decreased MSV-induced tumor formation in newborn NMRI mice and significantly increased the survival time of MSV-infected mice. In addition, upon oral administration to MSV-infected mice, (R)-PMPDAP showed marked antiretroviral efficacy. PMID- 8452367 TI - Synergy of levofloxacin (L-ofloxacin) and oxacillin against quinolone-resistant Staphylococcus aureus, measured by the time-kill method. AB - The synergistic activity of levofloxacin and oxacillin against levofloxacin resistant isolates of methicillin-resistant Staphylococcus aureus was tested by the time-kill method. The combination of levofloxacin at 1/4 the MIC for the isolate plus oxacillin at 8 micrograms/ml (< 1/4 the MIC) was synergistic against seven of nine isolates at 8 h, although no significant synergy was demonstrated at 24 h. This combination may prove to be effective against multidrug-resistant methicillin-resistant S. aureus, and further studies are warranted. PMID- 8452368 TI - Abnormal peptidoglycan produced in a methicillin-resistant strain of Staphylococcus aureus grown in the presence of methicillin: functional role for penicillin-binding protein 2A in cell wall synthesis. AB - Upon the addition of methicillin even at relatively low concentrations (5 mug/ml or 0.3% of the MIC) to the medium, methicillin-resistant staphylococci shift to the production of a new peptidoglycan with an abnormal muropeptide composition which may be the synthetic product of penicillin-binding protein 2A. PMID- 8452369 TI - Pharmacologic limits of the protective effect of polyaspartic acid on experimental gentamicin nephrotoxicity. AB - Polyaspartic acid (PAA) ameliorates experimental gentamicin nephrotoxicity despite marked accumulation of gentamicin in the renal cortex. The experiments described here probe the extent of PAA's nephroprotective action when increasing doses of gentamicin, in excess of an established nephrotoxic dose (40 mg/kg of body weight per day), are administered. After 10 days, virtually complete nephroprotection was conferred by PAA coadministered to animals receiving three times the nephrotoxic dose (120 mg/kg/day) of gentamicin. PMID- 8452370 TI - Comparison of the effects of 3'-azidothymidine with those of neutralizing antibodies on simian immunodeficiency virus infection in macrophages. AB - We previously showed that simian immunodeficiency virus-infected macaque macrophages contacting uninfected CD4+ lymphocytes caused extensive cell fusion and synthesis of phlogistic cytokines. In this study, macaque macrophage cultures inoculated with SIVmac251 and treated simultaneously with 10 microM 3' azidothymidine (AZT) became infected and produced small amounts of viral antigen (p27) but failed to fuse with CD4+ CEM174 cells. When AZT was added 1 to 3 days after virus inoculation, the infected cells caused fusion and the release of tumor necrosis factor and produced increasing amounts of p27. In contrast, neutralizing antibodies prevented infection when added at the time of virus inoculation, and they were much more effective than AZT in limiting virus replication, fusion cytopathic effect, and cytokine production when added up to 3 days postinoculation. Neutralizing antibodies may be more effective than AZT in reducing the virus load in the macrophage population and in preventing both cell fusion and the production of potentially pathogenic cytokines. PMID- 8452371 TI - Anti-Trichophyton mentagrophytes activity and percutaneous permeation of butenafine in guinea pigs. AB - We examined anti-Trichophyton mentagrophytes activity, cutaneous penetration, and skin localization of butenafine, a novel benzylamine antifungal agent. The following results were obtained. (i) In the guinea pig dorsal skin trichophytosis model, butenafine produced complete eradication of fungi from infected sites. Clotrimazole was active when animals were infected with 10(4) or 10(5) cells but was almost inactive when the inoculum size was 10(6) cells. (ii) The MICs of butenafine and clotrimazole against arthrospores of T. mentagrophytes KD-04 were 0.025 and 0.39 microgram/ml, respectively. (iii) When 0.2 ml of a 1% 14C butenafine solution was applied for 23 h/day for 7 days, high radioactivity corresponding to 250 to 500 micrograms of butenafine per g of skin in the epidermis, including the horny layer, was observed. (iv) Butenafine penetrates through transepidermal and transfollicular routes. The excellent therapeutic efficacy of butenafine on experimental dermatophytosis may be attributed to its low MIC and good penetration and distribution in the horny layer and hair follicles, where fungi reside. PMID- 8452373 TI - New turbidimetric assay for quantitation of viable bacterial densities. AB - A turbidimetric assay was developed and validated against Escherichia coli for the quantitation of viable bacterial densities. The Abbott MS-2 research system was employed for continuous 5-min measurements of optical density. A linear standard curve was obtained by regressing the initial bacterial density (log CFU per milliliter) against the time required for bacterial growth causing a 5% decrease in optical transmittance. Slope and intercept values obtained from eight standard curves showed excellent assay reproducibility. Results obtained by the turbidimetric assay compared favorably to those obtained by the conventional pour plate assay. Prior to the application of the new assay, possible interferences of postantibiotic effect induced by the test antibiotics were excluded. The turbidimetric assay, which is presumably more efficient and less expensive, was implemented for the time-kill studies of three different beta-lactams against E. coli. PMID- 8452372 TI - In vitro activity of CP-99,219, a new fluoroquinolone, against clinical isolates of gram-positive bacteria. AB - The in vitro activity of the fluoroquinolone CP-99,219 against gram-positive bacteria was compared with those of five other antimicrobial agents. Against ciprofloxacin-susceptible staphylococci and against streptococci, MICs were < or = 0.12 and < or = 0.5 microgram/ml, respectively. CP-99,219 was also more active than ciprofloxacin against ciprofloxacin-resistant staphylococci, most enterococci, Leuconostoc spp., and lactobacilli. PMID- 8452374 TI - Investigation of anabolic steroids in two taste aversion paradigms. AB - The aversive effects of estradiol have been studied in two different taste aversion paradigms. A similar investigation was undertaken for the anabolic androgenic steroids, nandralone and testosterone cypionate, using Rockland-Swiss mice. Experiments 1 and 2 used the brief exposure of a novel saccharin solution as the conditioned stimulus for taste aversion learning, and showed that anabolic steroids (1 mg) do not induce taste aversions. Instead, these hormones induced a small non-contingent increase in saccharin preference. Experiment 3 showed that daily nandralone administration (1 mg/day) had a greater anabolic effect than the same dose of testosterone cypionate. Experiment 4 paired the continuous exposure to a novel diet with daily nandralone injections, and showed that steroid treatment increased intake of the novel diet. When the novel diet was subsequently presented with the familiar diet in a two-choice preference test, there was no indication that an aversion was conditioned to the novel target diet. On the contrary, nandralone treatment significantly increased the preference for the novel diet. These experiments show that anabolic-androgenic steroids do not have aversive effects in mice, and that they may have positive consequences. PMID- 8452375 TI - Effects of interrupting an intraoral meal on meal size and meal duration in rats. AB - Most experiments on satiation do not separate the contribution to meal size of cumulative intake from that of time since meal onset. To assess the relative contributions of temporal and intake factors, the amount consumed of intraorally infused 12.5% glucose solution, delivered at a fixed rate of 1.0 ml/min, was assessed after tests that were interrupted for variable durations (Experiments I and II) beginning at different times within the test meal (Experiment I). Rats' meal size did not vary despite the imposition of single or multiple pauses which interrupted ingestion for as long as 38 min. These results show that, within this paradigm, the duration of the meal varies in service of an intake "goal". Such a defense of meal size requires accurate monitoring of the postingestive load despite its redistribution by continued gastric emptying during the imposed pauses in ingestion. PMID- 8452376 TI - Gender and age differences in food cognition. AB - Results from three studies relevant to a model of food cognition based on the evaluative dimensions pleasure, health, and convenience are reported. In the first study, discriminant analyses of the evaluative ratings (n = 248) of 35 meals and snacks yielded significant gender and age differences on the pleasure and health dimensions. Separate factor analyses of the pleasure and health ratings revealed that males and females grouped foods differently on these criteria. The factor analysis of convenience ratings suggested that males and females perceive the meaning of convenience differently. In the second study, 336 college students rated 27 meals on the three evaluative dimensions and also indicated their preferences for each meal. Multiple regression analyses showed that preferences could be significantly predicted, and other results showed that as compared to males, females give higher health, pleasure and convenience ratings to healthy meals. The third study employed a modified free association technique to investigate gender and age differences in the meanings of nine familiar foods. Data from 96 males and females aged 18 to 86 revealed a substantial variety of significant age and gender differences for specific foods. It is suggested that taken together, these results indicate important cognitive and affective sources for gender and age-related food attitudes. PMID- 8452377 TI - The milk mucus belief: sensations associated with the belief and characteristics of believers. AB - The belief that milk produces mucus is widespread in the community and is associated with a significant reduction in milk consumption. Sensations associated with milk drinking were reported by otherwise healthy believers and non-believers in the milk-mucus effect (N = 169) in an unstructured interview, with further responses prompted about the duration, type and amount of milk causing the effect. The site predominantly affected was the throat, with sensations related to difficulty in swallowing and perceived thickness of mucus and salivary secretions, rather than excessive mucus production. The effect required only a small amount of milk and was reported to be of short duration. The chronic respiratory symptom history and dairy product intake of 130 of these subjects were also assessed. Milk-mucus believers were different from non believers, reporting more respiratory symptoms and consuming less milk and dairy products. Symptoms consistent with the known effects of food allergy or intolerance were not reported. PMID- 8452378 TI - The milk-mucus belief: sensory analysis comparing cow's milk and a soy placebo. AB - A questionnaire designed to measure the "milk mucus effect" was based on sensations and symptoms after drinking milk reported in interviews with 169 individuals, 70 of whom held the belief that milk produces mucus. This was used to measure responses in a randomized, double-blind trial of a flavoured UHT cow's milk drink, compared with a similarly flavoured and constituted UHT soy milk drink. The soy placebo was indistinguishable from cow's milk in a pretest of 185 individuals. Of 14 milk-mucus effect indicator variables, three showed significant increases after consumption of 300 ml of the test drink. These were "coating/lining over the mouth, throat or tongue" (39% increase), "need to swallow a lot" (31% increase) and "saliva thicker, harder to swallow than before" (42% increase). However, these increases occurred in both milk and placebo groups. It is concluded that the effect measured is not specific to cow's milk, but can be duplicated by a non-cow's milk drink with similar sensory characteristics. PMID- 8452379 TI - [Recent trend on the development of new anticancer drugs]. AB - More than 35 candidate drugs have been under their clinical studies in Japan currently. These include antimetabolites, drugs originated from natural products, miscellaneous compounds and hormones. Since the time of appearance of cisplatin and taxol, we found the possibility to discover new active drugs against human solid cancers. Our recent clinical studies on topoisomerase inhibitors and microtubules inhibitors have also been proving the clinical usefulness of these drugs for cancer treatment. From now on, we have to think the drug development from ethical aspects, improving quality of life and prolonging the survival of the treated patients. For these purposes, we have to be careful to choose candidate drugs for their clinical trials. PMID- 8452380 TI - [Multi-institutional feasibility study of SDI test for its application to the adjuvant chemotherapy of gastric cancer]. AB - For the purpose to evaluate the feasibility of SDI test, a drug sensitivity test, against resected gastric cancer a multi-institutional study called as consisted of multiple institute the 16th Specified Study was planned by Japanese Foundation for Multidisciplinary Treatment of Cancer. SDI test was performed individually in 15 institutes in Japan using surgically resected specimens from the patients with gastric cancer. The adjuvant chemotherapy in each case was selected by randomized stratification. The anticancer drugs used were tegafur and one of the following three drug, mitomycin C (MMC), adriamycin (ADM) and cisplatin (CDDP). The drug sensitivity of each tumor was assayed by SDI test. The strict quality control was necessary to unify the method and the technique of this test in 15 institutes. Tumor bearing nude mice were delivered to each institute and the test was performed simultaneously. The data of this test were sent by personal computer to our Department. The clinical feasibility of this test will be evaluated after accumulation of cases for the statistic analysis. PMID- 8452381 TI - [In vitro chemosensitivity assay using a double-layer-agar system: human tumor cloning assay and thymidine incorporation assay]. AB - Human tumor cloning assay (HTCA) and thymidine incorporation assay (TIA) were both performed using a double-layer-agar system with continuous exposure of cells to standard anticancer drugs. The rate of evaluable assays was 44% (280 of 638 tumor samples) in HTCA and 48% (216 of 452) in TIA. When the tumor samples were restricted to the gastric and colorectal cancers, it was significantly higher in TIA than HTCA (p < 0.01). HTCA was 95% reliable for predicting in vivo resistance and 52% reliable for in vivo sensitivity, whereas TIA was 88% reliable for in vivo resistance and 44% for in vivo sensitivity. These results seem to suggest that it is unnecessary to select just clonogenic tumor cells among whole tumor cell population in assessing chemosensitivity of human tumors. The current study also indicates that chemotherapy with in vitro sensitive drugs assessed by TIA produced longer survival of the patients with stage III or IV gastric cancer. Most of clinical correlation trials including this study, however, have been performed retrospectively. The prospective study is necessary to determine whether drug selection by in vitro assays is superior to that by an experienced oncologist. In addition, further studies on pharmacokinetics of anticancer drugs are required to solve some other problems inherent to the current chemosensitivity assays. PMID- 8452382 TI - [Accordance of the chemosensitivity between clinical specimens and their xenografts in nude mice by SDI test and the value of in vivo chemosensitivity test using nude mice]. AB - We assessed the sensitivity to anticancer drugs by SDI (succinate dehydrogenase inhibition) test with 11 clinical specimens obtained from operated patients. The results were compared with those of xenografted specimen in nude mice, using the adjuvant part of the specimens assayed. Chemosensitivity of clinical specimens against 3 drugs is mitomycin (MMC), adriamycin (ADM) and cisplatin (CDDP), showed a good accordance (73%) with those of xenografted tumors. The drug sensitivity was considered to be one of the features of original tumors and to be well preserved in the xenografts in nude mice. We also studied in vivo experimental chemotherapy on 19 tumor lines in nude mice to compare the chemosensitivity with clinical response to the same chemotherapy observed in each donor patient. A close correlation (83% on responder, 100% on non-responder and the overall predicting accuracy rate were 95%) was shown, suggesting in vivo nude mouse assay having an excellent predictability for clinical results. PMID- 8452384 TI - [High clinical predictability of histoculture drug response assay (HDRA) for drug sensitivity of cancer of the digestive organs]. AB - Fresh surgical specimens from 250 patients with cancer were used for the histoculture drug response assay (HDRA) with MTT method. Scissor cut small pieces of the specimens were placed onto collagen-gel-matrix which was incubated in 24 well-plate dishes filled with medium containing mitomycin C (MMC), adriamycin (ADM), 5-fluorouracil (5-FU) or cisplatin (CDDP). The cutoff concentrations of the drugs used are 7.5 micrograms/ml for MMC, 15 micrograms/ml for ADM, 300 micrograms/ml for 5-FU and 20 micrograms/ml for CDDP. After 7 days incubation, the specimens were assessed the inability to reduce MTT. A 50% or greater inhibition of MTT reduction at the cutoff concentrations indicated in vitro sensitivity. The clinical effect of the drugs was evaluated according to the criteria of the Japanese Society for Cancer Therapy. Two hundred thirty two (93%) cases were evaluable, and in vitro and in vivo correlation was compared in 42 cases. Of the 33 patients whose tumors showed drug resistance in HDRA, 33 failed treatment with one or more of these agents. Of the nine patients whose tumors showed drug sensitivity in HDRA, six had chemo-responses (2 CRs and 4 PRs) for a total accuracy of 93% (34/42). The advantages of HDRA include, three-dimensional tumor cell growth in in vitro culture with cell to cell contact and maintenance of tissue architecture, 7 days to assess the effect of antitumor agents, ability to evaluate both growing and resting tumor cells, small amounts of specimen required for assay, and high evaluable and predictable rates for clinical use in designing optimal chemotherapy regimens for cancer patients. PMID- 8452383 TI - [Experimental and clinical study in vitro chemosensitivity test for succinate dehydrogenase inhibition test]. AB - The usefulness and problems in the succinate dehydrogenase inhibition (SDI) test as an in vivo chemosensitivity test were reviewed and discussed. SDI test is based on the correlation of succinate dehydrogenase activity with cell viability. The optimal condition of SDI test were evaluated with respect to concentration of anticancer drugs, incubation time, effect of sodium succinate on formazan production and enzymatic disaggregation of solid tumors. Analysis of the chemosensitivity of clinical tumors revealed that the origin of tumor, histological differentiation, DNA distribution patterns, estrogen receptor status in breast cancer, and difference of primary and metastatic lesions were critical for determining the chemosensitivity of tumor tissues. Correlation between in vitro sensitivity in the SDI test and in vivo clinical results of chemotherapy was evaluated. Since SDI test reflects cell viability and is a simple, rapid and inexpensive methods, it is appropriate both for clinical chemosensitivity testing and for the screening of anticancer drugs. PMID- 8452385 TI - [Comparison between leucovorin and cisplatin as a modulator of 5-fluorouracil]. AB - Currently, biochemical modulation for 5-fluorouracil (5-FU) by leucovorin (LV) and cisplatin (CDDP) seems one of the most successful chemotherapy for gastro intestinal tract cancers. The mechanism of the modulation is thought to increase intracellular 5, 10-methylenetetrahydrofolate (CH2-H4 folate) levels. The purpose of this study is to examine the effect of LV and CDDP as a modulator of 5-FU. Either 10, 200, 400 mg/kg of LV or 2, 4, 6 mg/kg of CDDP were administered intravenously to mice bearing Sarcoma-180. Two hrs. later, CH2-FH4 folate levels were measured in tumor, muscle and intestine by thymidylate synthase (TS) binding assay. As the results, after administration of 200, 400 mg/kg of LV or 4, 6 mg/kg of CDDP, CH2-H4 folate level was elevated. This elevation was dose-dependent in LV. In contrast, no more elevation was observed after 6 mg/kg of CDDP injection. There was much smaller increase of CH2-H4 folate level was observed in the muscle and intestine. We conclude that the elevation of CH2-H4 folate levels depends on the organ and this leads to the tumor specificity in these chemotherapy. PMID- 8452386 TI - [Phase I study of 5-fluorouracil and l-leucovorin]. AB - Leucovorin, given usually by i.v. injection or orally changes to 5, 10-methylene tetrahydrofolate in tumor as well as normal cells. And in normal FdUMP, an active metabolite of 5-FU, binds tightly to thymidylate synthase in the presence of cofactor, 5, 10-methylene tetrahydrofolate. This interaction leads to potentiate the cytotoxic effect of 5-FU by prolonged inhibition of thymidylate synthase. Phase I study using l-leucovorin (l-LV), an active form of leucovorin, combined with 5-FU, was conducted. In the weekly schedule, 5-FU was fixed to 600mg/m2, and l-LV dose was escalated from 125 mg/m2 to 250mg/m2, if toxicity was acceptable. On the other hand, in the five consecutive-day schedule, 5-FU was fixed to 370mg/m2 and l-LV was escalated from 25mg/m2 to 50mg/m2, 100mg/m2 and 200 mg/m2. l-LV 10mg/m2 was tested as reference. On weekly schedule of l-LV 250mg/m2, grade III diarrhea was seen in 2 cases and grade IV leucopenia was seen in one. In five consecutive-day schedule, at each dose of l-LV, stomatitis, nausea plus vomiting, anorexia, anemia and leucopenia were seen. However, the increase of toxicities were not seen by dose escalation of l-LV. Then, we have been conducted a randomized early phase II study using 250 mg/m2 of l-LV weekly (arm A) and 100mg/m2 (arm B) or 10mg/m2 (arm C) of l-LV for 5 consecutive days in gastric and colorectal cancer by multicenter cooperative study. Plasma concentrations of l-LV were maintained > 10(-5) mol/L for over 5 hrs. after 2 hrs. infusion of 250 mg/m2 of l-LV and for over one hr. after a rapid injection of 100mg/m2 of l-LV. PMID- 8452387 TI - [Treatment of advanced gastric and colorectal cancer with 5-FU, leucovorin and interferon-alpha]. AB - Twenty-four patients with advanced or relapsed gastric or colorectal cancer were treated with a combination of 5-fluorouracil (5-FU), leucovorin (LV) and interferon-alpha (IFN-alpha). 5-FU was administered by rapid intravenous infusion at 350 mg/m2 for 5 consecutive days. Intravenous bolus administration of LV 20 mg/m2 was given before each 5-FU administration. This combination was repeated every 3 to 4 weeks. IFN-alpha (HLBI), 6MU, was administered subcutaneously daily. Of 13 patients with gastric cancer, there were 2 PR, 4 NC and 7 PD, and among 11 patients with colorectal cancer, there were 1 CR, 8 NC and 2 PD. All 16 previously treated patients had no clinical response. Responses were seen in patients with no prior chemotherapy and with good performance status. Most common toxicities observed were leucopenia, fever, stomatitis and diarrhea, which were all tolerable and reversible. PMID- 8452388 TI - [Toxic effects of ifosfamide in the treatment of bone and soft tissue sarcomas]. AB - A total of 64 courses of ifosfamide (IFM) treatments for sarcoma patients were evaluated for toxic effects. A dose of 100 ml of 1/2 diluted Maalox by normal saline was instilled into urinary bladder with clump of catheter for 15 min for uroprotection instead of Mesna that was not available in Japan at that time. Forty-six courses of ifosfamide treatment in 12-16 g/m2 doses with daily Maalox instillation resulted only one hemorrhagic cystitis, while 18 courses at a dose of 6-10 g/m2 of IFM without Maalox eventuated in 5 cases of hemorrhagic cystitis. Forty-six courses of ifosfamide treatment at a dose of 12-16 g/m2 (mean dose of 14.4 g/m2) for 5 to 6 day continuous infusion were evaluated also for myelosuppression, nephrotoxicity, neurotoxicity, and other toxicities. Myelosuppression was acceptable, although the absolute neutrophil count of the 80% course was below 500. No patient showed neurotoxicity characterized by confusion or somnolence. No course resulted in abnormal serum creatinine elevation, although two of 46 courses caused an abnormal decrease of creatinine clearance. One patient had arrhythmia that required medical treatment after 5 courses of IFM treatment. PMID- 8452389 TI - [A case of complete remission of breast cancer with bilateral multiple lung metastases by combination therapy of MPA, THP, CPM and 5-FU]. AB - A 55-year-old female was admitted for right breast tumor with multiple bilateral lung metastases. Modified radical mastectomy (Auchincloss method) was carried out. And the combination chemoendocrine therapy was undertaken using CPA 100 mg p.o. days 1-18, THP 40 mg i.v. days 1, 8, 5-FU 500 mg i.v. days 1, 8 and MPA 1,200 mg p.o. daily. One month later, the lung metastases completely disappeared on chest CT gram. Nine courses of chemotherapy with the same drugs were undertaken intravenously every four weeks. This therapy has been continuously effective for one and half years now. These results suggested the importance of a severe adjuvant therapy for the initial phase of advanced breast cancer. PMID- 8452390 TI - [A case of breast cancer with thrombosis during treatment of lung metastasis]. AB - A 74-year-old female with lung metastasis of breast cancer was treated with chemo endocrine therapy (intravenous administration of epirubicin at 30 mg/2w, oral administration of UFT at 400 mg/day, alternate oral administration of medroxyprogesterone acetate at 800 mg/day and tamoxifen at 40 mg/day) and immuno therapy (intravenous administration of lentinan at 2 mg/w). Lung tumors decreased in size and number. At the same time, deep vein thrombosis of the lower extremities occurred, which caused multiple pulmonary embolization. In this case, several factors were suggested to cause thrombosis in the advanced or recurrent breast cancer patient. PMID- 8452391 TI - [Alterations in morphological and phenotypical features of leukemic cells relapse 7 years after onset in a case of acute non-lymphocytic leukemia]. AB - A case of acute non-lymphocytic leukemia who relapsed 7 years after the first remission is reported. The leukemic cells at onset had mature monocytic features with positive reactions for anti-CD14 antibody and alpha-NBE staining. By contrast, leukemic cells at relapse showed distinct morphological features from those at onset and lost their monocytic characters. No karyotypic abnormalities were found, but we could not exclude the possibility of secondary leukemia induced by the initial anti-leukemic chemotherapy. PMID- 8452392 TI - [A case of refractory multiple myeloma effectively treated with long-term oral etoposide]. AB - A sixty-two-year-old man was admitted to our hospital for diarrhea and fatigue on September 1, 1988. Laboratory examination revealed anemia and a high serum protein level with increased gamma-globulin. Although he had no apparent bony lesions, the bone marrow picture showing an increase of abnormal plasma cells and serum immunoelectrophoresis indicating the presence of monoclonal protein of IgG gamma type were compatible with multiple myeloma, stage IIIA. None of the following combinations of interferon alpha and ranimustine, cyclophosphamide and prednisolone, or melphalan and prednisolone were effective in reducing the level of serum M-protein. Therefore, we started daily oral administration of etoposide (25 mg/day) on February 21, 1989. Then the serum M-protein level was gradually reduced, and partial remission was achieved after 9 months' administration. After 27 months treatment the regimen was changed from daily to every second day administration, and finally stopped after 40 months. The patient has been in remission without etoposide to date. PMID- 8452393 TI - [Clinico-pharmacological study on UFT enteric-coated granules for gastric cancer patients]. PMID- 8452394 TI - Rhinolaryngoscopic examination of patients with the multiple chemical sensitivity syndrome. AB - Ten patients who met the Cullen case definition for the multiple chemical sensitivity syndrome were evaluated; a history was taken, and physical examination and fiberoptic rhinolaryngoscopy were performed. All patients had an initial chemical exposure, which was followed by multiple physical and mental complaints in response to subsequent exposure to a variety of odorous organic chemicals. Rhinitis was a prominent complaint in nine patients, but one patient denied any nasal symptoms. Rhinolaryngoscopic findings were abnormal in all patients; edema, excessive mucus, a cobblestone appearance of the posterior pharynx and base of the tongue, and mucosal injection were observed frequently. A particularly striking finding was focal areas of blanched mucosa that surrounded a prominent vessel. These results suggest that nasal pathology may be a prominent feature of this disorder. PMID- 8452395 TI - Multiple chemical sensitivities syndrome: toward a working case definition. AB - A study was conducted to identify clinical diagnostic criteria that experts regarded as major for categorizing patients as having multiple chemical sensitivities (MCS) syndrome. A cross-sectional survey of 148 medical practitioners with an interest in, or familiarity with, the condition was performed scoreable questionnaires were returned by 60.1% of those surveyed. The following five criteria, all based on self-reports, were selected as major for diagnosing the syndrome by more than 50% of the respondents: (1) symptoms are reproducible with exposure; (2) condition is chronic; (3) low levels of exposure result in manifestations of the syndrome; (4) symptoms resolve with removal of incitants; and (5) responses occur to multiple, chemically unrelated substances. It is proposed that the major criteria accepted by the majority of survey respondents be used provisionally as the basis for categorizing cases in investigations of MCS syndrome. PMID- 8452396 TI - Effect of ambient ozone on peak expiratory flow of exercising children in The Netherlands. AB - The potential effects of elevated ozone concentrations in The Netherlands were evaluated by the measurement of peak expiratory flow (PEF) of exercising children. Peak expiratory flow was measured with mini-Wright peak flow meters, both before and after out-door sports training. The relationship between PEF and ozone was investigated with individual regression analysis. The difference of PEF after and before training (delta PEF) and the PEF after training were used as dependent variables. The ozone concentration during the training and the 1-h maximum ozone concentration of the same and the previous day were used as independent variables. The highest observed 1-h maximum ozone concentration was 236 micrograms/m3. delta PEF was unrelated to the ambient ozone concentration during training. Peak flow measured after the training was positively correlated with ambient temperature. The high correlation between ozone and temperature prevented the evaluation of effects of the maximum ozone concentration of the same day on PEF after training. A small negative association of borderline statistical significance between PEF after training and previous-day maximum ozone was observed. PMID- 8452397 TI - Long-term ambient concentrations of total suspended particulates, ozone, and sulfur dioxide and respiratory symptoms in a nonsmoking population. AB - Seventh-day Adventist nonsmokers, who, subsequent to 1966, had resided within 8 km (5 miles) of their 1977 residence (N = 3,914), completed the National Heart and Lung Institute (NHLI) respiratory symptoms questionnaire in 1977 and again in 1987. For each participant, cumulative ambient concentrations of total suspended particulates (TSP), ozone, and sulfur dioxide (SO2) in excess of several cutoff levels were estimated by month and by interpolating ambient concentrations from state air-monitoring stations to their residential and workplace zip codes for the month. Statistically significant relationships between ambient concentrations of TSP and ozone, but not SO2, were found with several respiratory disease outcomes. Multivariate analyses adjusted for past and passive smoking and occupational exposures. Results are discussed within the context of standards setting for TSP and ozone. PMID- 8452398 TI - How should we think about chemically reactive patients? PMID- 8452399 TI - Community exposure to a paraquat drift. AB - A mixture of paraquat and water was applied, by helicopter, to agricultural fields near a residential community and near an associated commercial complex. Drift from the application passed directly over the community, which resulted in resident complaints to the local county agricultural department. A community survey was undertaken to determine what health consequences, if any, resulted from the drift. A comparison of 2-wk self-reported symptom rates between the exposed community and three historical control communities indicated that 10 symptoms were elevated significantly at p < .05: cough, diarrhea, eye irritation, headache, nausea, rhinitis, throat irritation, trouble breathing, unusual tiredness, and wheezing. An internal comparison, which predicted symptom rates by an index of paraquat exposure (smelling an unusual odor in the prior 2-wk period), indicated fever (relative risk [RR] = 11.97) and nausea (RR = 3.75) to have elevated relative risks. Odor perception also predicted the report of a greater than the average number of symptoms. Based upon these findings, it was concluded that these residents probably did experience an increase in health symptoms from the drift. It is recommended that paraquat not be sprayed near residential communities. PMID- 8452400 TI - Preoperative evaluation of patients for liver resection. Appropriate CT imaging. AB - OBJECTIVE: The authors determined which combination of computed tomography scans is most helpful for preoperative assessment of patients with liver tumors. SUMMARY BACKGROUND DATA: Multi-institutional studies have shown that the most important prognostic factors for selection of patients with metastatic colorectal cancer considered for liver resection are: Dukes' stage of primary tumor, the number of hepatic metastases if greater than 3, the presence of extrahepatic cancer, and the ability to resect tumors with an adequate margin (> 1 cm.) Therefore the ability to predict the presence of extrahepatic disease and the number and location of hepatic tumors are important in these patients. METHODS: One hundred and nine consecutive patients with evidence of hepatic tumors were evaluated by computed tomography with arterial portography (CTAP) and abdominal computed tomography after a 4-hour delay (CT-D). Results of these studies and conventional computed tomography (CT-C) were compared with findings at operation. RESULTS: CTAP proved to be the most sensitive test for assessing distribution of intrahepatic disease. CT-D was no more sensitive than CT-C for the detection of hepatic or extrahepatic disease. CONCLUSIONS: CT-C in concert with CTAP provides the most reasonable CT evaluation of patients considered for operation for the treatment of hepatic tumors. PMID- 8452401 TI - Factors associated with successful laparoscopic cholecystectomy for acute cholecystitis. AB - OBJECTIVE: This article determined which preoperative data correlated with successful completion of a laparoscopic cholecystectomy in patients with acute cholecystitis. SUMMARY BACKGROUND DATA: Although laparoscopic cholecystectomy is the procedure of choice in chronic cholecystitis, its use in acute cholecystitis may be associated with higher costs and complication rates. It is not known which patients with acute cholecystitis are likely to require conversion to open cholecystectomy based on preoperative data or if a cooling-off period with medical therapy can diminish inflammation and increase the chance of successful laparoscopic cholecystectomy. METHODS: All laparoscopic cholecystectomies done by the authors between 10/90 and 2/92 were reviewed. Data on cases of acute cholecystitis were prospectively collected on standardized data forms. RESULTS: Twenty of 281 laparoscopic cholecystectomies were done for acute cholecystitis; 7/20 patients with acute cholecystitis required conversion to open cholecystectomy compared with 6/281 patients undergoing elective operation for chronic cholecystitis. In patients with acute cholecystitis the interval from admission to cholecystectomy in the successful cases was 0.6 days vs. 5 days in the cases requiring conversion to open cholecystectomy (p = .01). Cases requiring conversion to open cholecystectomy also had higher WBC (14.0 vs. 9.0, p < .05), alkaline phosphatase (206 vs. 81, p < .02, and APACHE II scores (10.6 vs. 5.1, p < .05). Ultrasonographic findings such as gallbladder distention, wall thickness, and pericholecystic fluid did not correlate with the success of laparoscopic cholecystectomy. Patients converted from laparoscopic to open cholecystectomy required more operating room time (120 min vs. 87 min, p < .01) and more postop hospital days (6 vs. 2, p < .001). CONCLUSIONS: Laparoscopic cholecystectomy for acute cholecystitis should be done immediately after the diagnosis is established because delaying surgery allows inflammation to become more intense, thus increasing the technical difficulty of laparoscopic cholecystectomy. PMID- 8452402 TI - Benign biliary strictures. Surgery or endoscopy? AB - OBJECTIVE: This study compared the results of surgery and endoscopy for benign biliary strictures in one institution, over the same period of time and with the same outcome definitions. SUMMARY BACKGROUND DATA: Surgery is considered the treatment of choice, offering more than 80% long-term success. Endoscopic stenting has been reported to yield similar results and might be a useful alternative. METHODS: In this nonrandomized retrospective study, 101 patients with benign biliary strictures were included. Thirty-five patients were treated surgically and 66 by endoscopic stenting. Patient characteristics, initial trauma, previous repairs, and level of obstruction were comparable in both groups. Surgical therapy consisted of constructing a biliary-digestive anastomosis in normal ductal tissue. Endoscopic therapy consisted of placement of endoprostheses, with trimonthly elective exchange for a 1-year period. RESULTS: Mean length of follow-up was 50 +/- 3.8 and 42 +/- 4.2 months for surgery and endoscopy, respectively. Early complications occurred more frequently in the surgically treated group (p < 0.03). Late complications during therapy, occurred only in the endoscopically treated group. In 46 patients, the endoprostheses were eventually removed. Recurrent stricturing occurred in 17% in both surgical and endoscopic patients. CONCLUSIONS: Surgery and endoscopy for benign biliary strictures have similar long-term success rates. Indications for surgery are complete transections, failed previous repairs, and failures of endoscopic therapy. All other patients are candidates for endoscopic stenting as the initial treatment. PMID- 8452403 TI - Effect of portosystemic shunting on PGI2 and glucagon levels in humans. AB - OBJECTIVE: This study determined if the proposed mediators of splanchnic blood flow, prostacyclin and glucagon, were elevated in patients with portal hypertension undergoing portal systemic shunts. SUMMARY BACKGROUND DATA: Chronic portal hypertension results in increased portal venous pressure and increased splanchnic blood flow. Animal studies have suggested prostacyclin or glucagon, potent vasodilators, as potential mediators of this increased flow. Correlative clinical studies have been difficult to perform due to the wide variation in degree of portal-systemic shunting and the frequent association of parenchymal liver disease in patients with cirrhosis. METHODS: The authors measured portal and systemic hemodynamics in PGI2 and glucagon levels in patients with portal hypertension due to cirrhosis (partial portal systemic shunt) and Budd-Chiari syndrome (complete portal systemic shunt) undergoing portal systemic shunts and in porto normotensive patients undergoing exploratory laparotomies. RESULTS: PGI2 levels in portal hypertension were significantly increased over normal, and prostacyclin in Budd-Chiari patients were increased significantly over patients with cirrhosis. Both PGI2 and portal venous pressure decreased significantly after portal systemic shunting, and prostacyclin levels correlated directly with portal venous pressure (R = 0.37, p < 0.05). CONCLUSIONS: This is the first evidence in humans supporting the hypothesis that PGI2 is elevated in portal hypertension and is related to both the degree of portal venous obstruction and portal pressure. PGI2 probably has a role in the abnormal splanchnic hemodynamics of human portal hypertension. PMID- 8452404 TI - Relationship between gastric acid secretion and the rate of recurrent ulcer after parietal cell vagotomy. AB - OBJECTIVE: This study assessed the effect of gastric secretion on the rate of recurrent ulcer after parietal cell vagotomy for duodenal ulcer. SUMMARY BACKGROUND DATA: Three hundred patients who underwent parietal cell vagotomy for duodenal ulcer between 1975 and 1986 were evaluated. The mean follow-up period for 280 patients was 5 years. METHODS: The gastric secretion tests concerned basal acid output (BAO) and peak acid output stimulated by pentagastrin or insulin. Tests were preoperative for 172 patients and postoperative for 118. RESULTS: At the end of that time, the overall incidence of symptomatic recurrent ulcer was 15%. Two criteria were shown to be important predictors of recurrent ulcer: preoperative BAO > 7 mmol/hr, for which the recurrence rate 5 years after vagotomy was 30% versus 11% for values below this threshold (p = 0.01), and postoperative BAO > 1.4 mmol/hr, for which the recurrence rate at 5 years was 72% versus 8% for lower values (p = 0.0001). All patients with recurrent ulcer had either a postoperative BAO > 7 mmol/hr and/or a postoperative reduction in BAO < 80%. CONCLUSION: Preoperative BAO > 7 mmol/hr and postoperative BAO > 1.4 mmol/hr were shown to be factors predictive of RU. All patients with RU presented either with preoperative BAO > 7 mmol/hr and/or a reduction in BAO < 80%. Consequently, in our opinion, these criteria could be used either to select patients for vagotomy or to assess the effectiveness of vagotomy of different types, especially those performed by celioscopy. PMID- 8452405 TI - Computed tomography in the evaluation of children with blunt abdominal trauma. AB - OBJECTIVE: This study determined the sensitivity, specificity, and accuracy of CT in pediatric patients with blunt trauma. Correlation of the CT-identified injuries and intraoperative findings with comparison to the results of DPL was performed. SUMMARY BACKGROUND DATA: Clinical evaluation frequently is unreliable in determining the presence of intra-abdominal injury in children with blunt trauma. Peritoneal lavage has been used to establish the need for operative intervention and has been found to be safe, efficient, and reliable (98%). In many institutions, abdominal CT scans are used to evaluate these children. Because most reports involve nonoperative management, operative confirmation of CT-identified injuries is available only for those children in whom nonoperative treatment is unsuccessful. METHODS: Sixty children sustaining blunt abdominal trauma were included in the study. CT scans with both oral and IV contrast were performed before open lavage, and positive results were confirmed by operation in 18 patients. RESULTS: CT had a sensitivity of 67%, however, only 60% of the actual organ injuries were identified by the scan. In contrast, DPL has a sensitivity of 94%. Both studies were equally specific (100%). DPL was also more accurate, 98% as compared with 89% for CT. CONCLUSIONS: Although the abdominal CT scan is useful in evaluating children with blunt abdominal trauma, a number of significant injuries were missed. Based on the low sensitivity of the CT, the authors suggest diagnostic peritoneal lavage may offer advantages over CT as the initial study in the evaluation of children with blunt abdominal trauma. PMID- 8452406 TI - Comparison of postoperative mortality in VA and private hospitals. AB - OBJECTIVE: This study compared unselected VA (Department of Veterans Affairs) and private multi-hospital postoperative mortality rates. In the absence of national standards for postoperative mortality rates and in view of the unique volume and range of surgical procedures studied, the second objective is to help establish national standards through the dissemination of these postoperative mortality norms. SUMMARY BACKGROUND DATA: Public Law 99-166, Section 204, enacted by Congress December 3, 1985, required that the VA compare postoperative mortality and morbidity rates for each type of surgical procedure it performs with the prevailing national standard and analyze any deviation between such rates in terms of patient characteristics. METHODS: The authors compared postoperative mortality in the VA to that in private hospitals, adjusting for the patient characteristics of age, diagnosis, comorbidity, or severity of illness. We used a total of 830,000 patients discharge records (323,000 VA and 507,000 private patients) from 1984 through 1986 among 309 individual surgical procedures within 113 comparison surgical procedures or procedure groups. RESULTS: The authors found no significant differences in postoperative mortality rates between the VA and private hospital systems for 105 of the 113 surgical procedures or procedure groups. VA postoperative mortality rates that were higher than those in private hospitals were found for suture of ulcer, revision of gastric anastomosis, small to-small intestinal anastomosis, appendectomy, and reclosure of postoperative disruption of abdominal wall (p = 0.05). Vascular bypass surgery, portal systemic venous shunt, and esophageal surgery showed a significantly lower postoperative mortality in the VA as compared with that in private hospitals (p = 0.05). CONCLUSIONS: VA postoperative mortality in 113 surgical procedures or procedure groups is comparable to that in private hospitals. PMID- 8452407 TI - Effect of total parenteral nutrition plus morphine on bacterial translocation in rats. AB - OBJECTIVE: This study tested the hypothesis that gut stasis induced by parenteral morphine sulfate (MS) leads to enhanced bacterial translocation in rats on total parenteral nutrition (TPN). SUMMARY BACKGROUND DATA: TPN and MS are common adjuncts in the care of critically ill patients. TPN is known to provoke a variable degree of translocation. MS induces gut stasis with an accompanying bacterial overgrowth. The effect of these two treatments in combination on translocation is not known. METHODS: Rats were provided with central and subcutaneous lines for the continuous infusion of nutrients and drugs, respectively. Intestinal transit was assessed by the caudal movement of a fluorescent marker intubated into the proximal duodenum. Quantitative bacteriology was carried out from various segments of the gut and from ileocecal mesenteric lymph nodes (MLN), spleen, liver, and systemic blood obtained by cardia puncture on sacrifice at 96 hours. RESULTS: Transit was unchanged by TPN alone but prolonged when given in combination with MS. Bacterial overgrowth was also enhanced by MS and increased the bacterial translocation to MLN from 50% of animals with TPN, to 100% in those receiving both TPN and MS; the colony-forming units per MLN increased from 33 +/- 14 with TPN alone to 2079 +/- 811 (STD) with TPN plus MS. Furthermore, no bacteria were found at systemic sites with TPN alone, but in 93.3% of animals receiving TPN and MS. In a subgroup of rates provided with glutamine in TPN, the TPN plus MS effects on translocation were not reversed. CONCLUSIONS: These observations demonstrate the important role that morphine plays in promoting translocation, presumably by disrupting fasting motility and enhancing bacterial overgrowth. PMID- 8452408 TI - A serial study of the erythropoietic response to thermal injury. AB - OBJECTIVE: Since controversy exists over whether erythropoietin levels are increased or decreased after thermal injury, a prospective study was performed to answer this question as well as to characterize the erythropoietic response to thermal injury. SUMMARY BACKGROUND DATA: The concept of using erythropoietin to reduce the need for blood transfusions after thermal injury is attractive. However, since the etiology of burn anemia is both unclear and multifocal, prior to initiating a trial of erythropoietin therapy, it will be necessary to better define the erythropoietic response to thermal injury. METHODS: Twenty-four burn patients with a mean burn size of 31 +/- 18% had serial measurements of serum iron, total iron binding capacity (TIBC), ferritin, erythropoietin, transferrin saturation, hemoglobin, and reticulocyte counts performed on burn days 1, 3, 5, 7, 10, 14, and then weekly. RESULTS: The erythropoietic response was characterized by a decrease in hemoglobin levels as well as serum iron, TIBC, and transferrin saturation (p < 0.05). Ferritin and erythropoietin levels increased as did the reticulocyte count. The erythropoietin response to anemia appeared to be at least grossly intact, since there was an appropriate inverse relationship between the degree of anemia and the magnitude of the erythropoietin response (r2 = .61, p < 0.00001). CONCLUSIONS: Since the erythropoietin levels of these anemic burn victims reached supranormal levels and they manifested a moderate reticulocytosis, the role of replacement erythropoietin therapy after thermal injury requires further study. PMID- 8452409 TI - Sequential anti-core glycolipid immunoglobulin antibody activities in patients with and without septic shock and their relation to outcome. AB - OBJECTIVE: This study follows the sequential changes in anti-lipopolysaccharide antibodies in infected patients with and without septic shock. SUMMARY BACKGROUND DATA: A relation between high endogenous levels of anti-LPS antibodies and protection against bacteremia and septic shock in at-risk patient groups has been observed. However, information on the daily follow-up and kinetics of apparition or disappearance of anti-LPS antibody activities and their relations with the protective properties of the different immunoglobulin classes has not been clearly investigated. METHODS: Two hundred and five septic surgical patients were studied during their stay in the intensive care unit during a period of 3 years. Among these patients, septic shock developed in 54 and 47 died. A sensitive ELISA was used to study circulating IgM and IgG antibodies to the core glycolipid (CGL) region of Salmonella minnesota R595. The activities were measured each day when sepsis occurred and every hour during septic shock. RESULTS: Anti-CGL IgM activity was found in 32% of the septic patients. This response, however, most often appeared to be transient. A strong correlation was observed between the occurrence of septic shock and the absence of anti-CGL IgM activity on admission to the ICU (p < 0.02). Anti-CGL IgG activity was detected in 82% of the patients and better correlated with outcome for patients with high or rising activities during their hospitalization (p < 0.0005). In patients with septic shock or irreversible organ failure, a fall in the anti-CGL IgG activity was observed before death, suggesting that the IgG antibodies were consumed during this acute event. Therefore, the anti-CGL IgG activity measured by ELISA could be used as a marker of the evolution of the illness. CONCLUSIONS: Our observations demonstrate the interest to follow-up the evolution of the anti-CGL antibodies during sepsis. The fall of these antibodies during septic shock and in patients who died was an additional argument to perform, as an additive form, passive antibody therapy to decrease lethality in this group of patients. PMID- 8452410 TI - Treatment of anal incontinence by an implantable prosthetic anal sphincter. PMID- 8452411 TI - Current management of malignant melanoma. PMID- 8452412 TI - Unsocialized medicine: the decline of surgical collegiality. PMID- 8452413 TI - Measurement of total DNA to assess lung cancers. PMID- 8452414 TI - Evolving applications of the maze procedure for atrial fibrillation. PMID- 8452415 TI - When does one replace the heart in ischemic cardiomyopathy? PMID- 8452416 TI - Third-time coronary artery bypass grafting: midterm results. AB - Minimal data are available regarding the results of patients who have undergone myocardial revascularization more than twice. The records of 13 consecutive patients who underwent a coronary artery bypass procedure for the third time were reviewed. The indication for operation was unstable angina in all patients. All patients were placed on cardiopulmonary bypass through a median sternotomy. The mean number of bypass grafts placed at the third operation was 1.9 (range, 1 to 3 grafts). A new internal mammary artery graft was placed in 6 patients (2 had prior internal mammary artery grafts). Hospital mortality was 7.7% (1/13). The single death was due to incomplete revascularization in a patient with poor distal vessels. Three patients required intraaortic balloon pump support postoperatively, and 2 patients had prolonged ventilatory insufficiency. There have been no late deaths. The 12 survivors have been followed up a mean of 44 months (range, 6 to 90 months). Four remain asymptomatic; 5 have mild angina easily controlled with medication. All except 1 are in improved condition compared with their preoperative status. We conclude that a third myocardial revascularization can be performed with low mortality and morbidity and with the expectation of long-lasting symptomatic improvement. PMID- 8452417 TI - Penetrating injuries of the aortic arch and its branches. AB - Acute cardiac failure, pulmonary edema, and ischemia of the brain, cord, and other structures pose special problems with trauma to the aortic arch and its branches. Data on 93 such cases are reported. Diagnosis was made by clinical examination in hemodynamically unstable patients and led to immediate operation in 61.3%. Patients in stable condition had angiography, which localized the injury and allowed planning of incision and bypass shunts. In left subclavian artery injuries, anterior thoracotomy was best for proximal control regardless of wound entry sites; midline sternotomy with sternocleidomastoid extension was usually adequate for other vessels. Flow was reestablished in all carotid injuries; there were no neurological complications. Temporary or permanent bypass shunts during periods of proximal aortic occlusion were valuable in decreasing cardiac afterload, maintaining circulation to the brain, and allowing an unhurried methodical approach to the hematoma. Occlusion of one or more venae cavae alleviated acute cardiac dilatation during brief periods of ascending aortic clamping. Associated trauma contributed to the high mortality. PMID- 8452418 TI - DNA ploidy pattern of each carcinomatous component in adenosquamous lung carcinoma. AB - The relationship between adenocarcinomatous and squamous carcinomatous components in 12 surgically resected adenosquamous lung carcinomas was analyzed using DNA flow cytometry. Well-preserved parts of the tumor showing either adenocarcinoma or squamous cell carcinoma were identified on paraffin blocks. The cells obtained from each component were stained with propidium iodide for DNA flow cytometry. In the analysis of DNA flow cytometry, both components in the same tumor were defined as being related to each other when they showed diploidy or when at least one DNA index of abnormal clones between two aneuploid components was identical. According to these criteria, 8 (67%) of the 12 tumors showed a relationship between adenocarcinomatous and squamous carcinomatous components. This suggests that, despite the different phenotypes, both components of some adenosquamous lung carcinomas may share similar biological characteristics. PMID- 8452419 TI - Recycling of the internal mammary artery in coronary reoperation. AB - In 5 patients undergoing a coronary artery reoperation, the internal mammary artery graft was taken down and reused. No special problems were encountered perioperatively or postoperatively. Because the number of grafts and distal anastomoses performed in coronary reoperations is increasing, lack of suitable graft conduits will be a problem in the future. Recycling an internal mammary artery graft may be an option to achieve good revascularization in some coronary reoperations. PMID- 8452420 TI - Anomalous course of the left brachiocephalic vein. AB - An anomalous course of the left brachiocephalic vein beneath the aortic arch was identified in 7 patients undergoing surgical repair of congenital cardiac malformations. Six of these patients had the morphologic features of tetralogy of Fallot including severe obstruction to the right ventricular outflow tract and a right aortic arch. A review of the literature reveals this to be an uncommon anomaly. When it is present, however, it is frequently associated with a ventricular septal defect, obstruction of the right ventricular outflow, and aortic arch anomalies. This anomaly can be documented by echocardiography, at cardiac catheterization, or intraoperatively. The presence of a subaortic left brachiocephalic vein may have implications for the conduct of surgical procedures, especially in the setting of tetralogy of Fallot. PMID- 8452421 TI - Primary repair of iatrogenic thoracic esophageal perforation and Boerhaave's syndrome. AB - Ten patients seen at our unit over a 24-month period with either iatrogenic (n = 5) or spontaneous thoracic esophageal perforations (n = 5) were retrospectively reviewed. Five patients were seen within 24 hours of onset of symptoms, and 5 were seen after 24 hours or later. There was no significant difference in the presentation or subsequent clinical course in patients seen less or more than 24 hours after the onset of symptoms. Nine patients underwent primary repair together with drainage of the mediastinum, and in 1 of these a Heller's myotomy was also performed for achalasia. One patient had a two-stage esophagogastrectomy for a benign esophageal stricture. One patient (10%) with a spontaneous perforation died 48 hours after operation and was found at postmortem examination to have an in situ carcinoma at the site of the perforation. Four patients (40%) had nonfatal complications. Fistulas developed in 3 patients (30%); in 1 of these patients a second thoracotomy and a further rib resection was required for drainage of a mediastinal abscess. An esophago-cutaneous fistula and a persistent mediastinal abscess developed in 1 patient (10%) and necessitated two further thoracotomies for effective drainage. The mean hospital stay was 38.4 +/- 25.4 days (range, 16 to 76 days). The findings of this study suggest that primary repair combined with a drainage procedure is the treatment of choice for patients with a perforated intrathoracic esophagus, including those seen more than 24 hours after the onset of symptoms. PMID- 8452422 TI - Cox/maze procedure for atrial septal defect with atrial fibrillation: management strategies. AB - Atrial fibrillation is found at late follow-up in approximately half of all adults who have had correction of atrial septal defect, even if it was not present preoperatively. These patients are thus exposed to the risks of stroke and chronic drug therapy even after a successful operation. Simultaneous surgical correction of atrial septal defect and atrial fibrillation was accomplished in a 52-year-old man by means of the Cox/maze procedure. The small added risk and the substantial benefit of eliminating atrial fibrillation suggest that this approach is warranted in selected adults with atrial septal defect. PMID- 8452423 TI - Technique for resecting primary and metastatic nonbronchogenic tumors of the thoracic outlet. AB - Although primary or metastatic nonbronchogenic tumors infrequently arise in or involve the thoracic outlet, they represent a major surgical challenge because of their tendency to encapsulate outlet structures. Fourteen patients with a histologically proven primary (n = 8) or metastatic (n = 6) nonbronchogenic outlet tumor were treated by an anterior transcervical approach, including an L shaped cervicotomy extended into the deltopectoral groove, resection of the internal half of the clavicle, and, in the case of tumor involvement, resection of the jugular and subclavian veins, phrenic nerve, subclavian artery, brachial plexus, and ribs. All patients underwent a radical resection. Tumors extended to bony (usually the first rib), muscular (usually the anterior scalenus muscle), and nerve (usually the phrenic nerve) outlet structures in 8, 10, and 7 patients, respectively. Ten patients had involvement of outlet vessels: 6 had simple ligature (n = 5) or wedge resection (n = 1) of the subclavian vein and related branches, 1 had revascularization of both the subclavian vein by an end-to-end anastomosis and the subclavian artery by a ringed polytetrafluoroethylene graft, 1 had revascularization of the subclavian artery alone, and 2 had revascularization between the left brachiocephalic vein and superior vena cava (ringed polytetrafluoroethylene graft). Follow-up venograms showed complete patency of the anastomoses. There was one postoperative death (7%) due to multiorgan system failure. Other complications were mild and short-lasting. With a median follow-up of 3.4 years, all patients but 1 (who had systemic progression) are alive and disease free 3 to 127 months postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452424 TI - Cardiopulmonary bypass and cellular immunity: changes in lymphocyte subsets and natural killer cell activity. AB - To investigate whether cell-mediated immunity responses are suppressed or activated by the effect of cardiopulmonary bypass (CPB), we studied peripheral blood lymphocyte subsets and antibody-dependent cell-mediated cytotoxicity in 52 adult patients who had undergone open heart operations. Lymphocyte function also was studied with regard to mixed lymphocyte reaction, which indicates the amount of DNA synthesis of lymphocytes, and natural killer (NK) cytotoxicity, which represents the killing activity of NK cells on the tumor cells (K-562), in 11 patients. The total T lymphocyte (OKT3+ and OKT11+) number showed no significant change during CPB. Suppressor/cytotoxic T cell (OKT8+) and NK cell (Leu7+ and Leu11+) numbers were found to be remarkably increased. However, helper/inducer T cell (OKT4+) and B cell (Leu12+) numbers were decreased during CPB. Antibody dependent cell-mediated cytotoxicity was elevated during CPB. All of these changes were almost returned to the preoperative levels by the seventh day after operation. Mixed lymphocyte reaction and NK cytotoxicity were also activated during CPB. The results show that heart operations in which cardiopulmonary bypass is used are associated with activation of cytotoxic cell-mediated immunity. PMID- 8452425 TI - Relation between choice of prostheses and late outcome in double-valve replacement. AB - The purpose of this study was to determine if the combination of a mechanical and bioprosthetic valve in the aortic and mitral positions influences late morbidity and mortality when compared with patients who had dual mechanical or dual bioprosthetic valves inserted. We reviewed the course of 89 hospital survivors of combined aortic and mitral valve replacement. The mean postoperative follow-up interval was 6.6 years, with a total follow-up of 583 years (98% complete). At 12 months after operation, mean functional class decreased from 3.1 to 1.7 (p < 0.05) and mean cardiac index increased from 2.1 to 2.5 L.min-1.m-2 (p < 0.05). Actuarial survival for the 89 patients (exclusive of < 30-day or in-hospital mortality, 14%) was 70%, 51%, and 33% at 5, 10, and 15 years. Freedom from reoperation was 93%, 78%, and 68%, and freedom from combined thromboembolism and anticoagulant-related hemorrhage was 82%, 60%, and 50%. These results show that there was no difference in overall survival in patients with dual mechanical valves, dual bioprosthetic valves, or a combination of both types at 15 years. There was, however, a lower reoperation rate in the group with dual mechanical valves as compared with the group with dual bioprosthetic valves (p < 0.05 at 10 years) or with a combination of valves (p < 0.05 at 15 years). The higher the number of mechanical valves the higher the combined risk of thromboembolism and anticoagulant-related hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452426 TI - Open mitral commissurotomy: fourteen- to eighteen-year follow-up clinical study. AB - From May 1974 to December 1978, 159 patients with mitral stenosis underwent open mitral commissurotomy at our institution. Follow-up data were complete in 96.8%, with a mean follow-up of 13.7 years (range, 14 to 18 years). Preoperatively, most patients (n = 94) were in functional class III or IV. Valve calcification was found in 18 patients (11.3%), left atrial thrombosis was found in 21 (13.2%), and the subvalvular apparatus was affected in 105 (66%). When a residual insufficiency was detected during the operation, a mitral annuloplasty was performed (n = 43). There was one hospital death (0.6%) and 15 late deaths (9.5%). Actuarial survival at 15-year and 18-year follow-up is 89.4% +/- 3% and 75.2% +/- 10.8%. Fifteen patients (9.7%) had a thromboembolic episode 1 to 189 months after operation (mean, 104.3 months). Eleven patients (7%) required reoperation 3 to 183 months after operation (mean, 110.1 months). Freedom from reoperation at 18-year follow-up was 91.9% +/- 2.7%. Event-free actuarial survival at 15-year and 18-year follow-up was 73.4% +/- 4.2% and 54.3% +/- 10.5%. Most patients (n = 131) are in class I or II. Open mitral commissurotomy represents a safe surgical alternative for treating mitral stenosis, allowing a complete removal of atrial thrombosis if present. This long-term follow-up clinical study encourages us to persist in this successful surgical repair of mitral stenosis. PMID- 8452427 TI - Pulmonary artery size and clinical outcome after the modified Fontan operation. AB - The maximum cross-sectional area of the central pulmonary arteries indexed to the body surface area (pulmonary artery index [PAI]) was measured preoperatively from angiograms in 173 patients evaluated for a Fontan-type operation between 1981 and June 1989. Of these, 34 patients underwent another palliative procedure, 8 primarily on the basis of small pulmonary arteries (PAI, 106 to 167 mm2/m2). The mean PAI of this group was significantly smaller than the mean PAI of the remaining 139 patients who underwent a Fontan operation (136 +/- 20 versus 310 +/ 113 mm2/m2) (p < 0.001). The patients who underwent a Fontan operation were evaluated according to three overlapping end points: (1) hospital death or takedown of repair (12.2%), (2) early failure (cumulative death or takedown of repair within 6 months of operation) (16.5%), and (3) early failure or persistent effusions (33.8%). With regard to these end points, no significant difference in pulmonary artery size could be found between patients having a favorable or unfavorable outcome. However, among a low-risk subset of 30 patients with tricuspid atresia, those with "early failure or persistent effusions" had significantly smaller pulmonary arteries than those with a good outcome (PAI, 185 +/- 47 versus 276 +/- 83 mm2/m2) (p < 0.01). The postoperative transpulmonary gradient of the 8 patients with the smallest pulmonary arteries who underwent a Fontan operation (all PAIs < 170 mm2/m2) was significantly greater than that of the rest of the study group (9.88 +/- 2.3 versus 8.13 +/- 2.3 mm Hg) (p < 0.04).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452428 TI - Effects of external stenting on wall thickening in arteriovenous bypass grafts. AB - Late occlusion of the saphenous vein graft appears to result in part from wall thickening as an adaptation to increased mean wall stress. Using an established pig model of arteriovenous bypass grafting, the effect of reducing wall stress with an external porous polytetrafluoroethylene stent was investigated. Segments of autologous saphenous vein were implanted by end-to-end anastomoses into both carotid arteries, with one graft supported by a stent 4 mm in diameter. Increases in graft wall dimensions were quantified 4 weeks later by computer-aided planimetry of transverse histological sections. The contribution of hyperplasia (i.e., cell proliferation) to the changes observed was further clarified by measurements of DNA concentration. All grafts showed an increase in external size, but this was restricted by stenting. All grafts also showed an increase in cross-sectional area of the tunica media and tunica intima that was only partly accounted for by an increase in DNA concentration, which indicated that both hyperplasia and hypertrophy had occurred. Stented grafts showed less enlargement of the media but greater enlargement of the intima. Overall wall size was therefore similar in stented and unstented grafts. Stented grafts showed less increase in DNA concentration than unstented grafts. In stented grafts, the residual luminal cross-sectional area was significantly less than in unstented grafts. The data show that external stenting reduces medial enlargement and hyperplasia but increases encroachment of the intima into the lumen. Because final luminal size is thought to be of paramount importance in maintaining long term patency, external stenting is unlikely to be of benefit. PMID- 8452429 TI - Completion pneumonectomy and thoracoplasty for bronchopleural fistula and fungal empyema. AB - Achieving sterilization of the postpneumonectomy space and bronchial healing may be difficult when active granulomatous infection of the pleural space and lung parenchyma is present at the time of operation. Three patients with chronic bronchopleural fistula, fungal empyema, and fungal cavities of the remaining ipsilateral lobe were managed with one-stage completion pneumonectomy and modified eight-rib thoracoplasty. Two patients had infection with Aspergillus fumigatis and 1 patient had Coccidioides immitis. Two patients had received mediastinal radiation after prior upper lobectomy for carcinoma of the lung. Two patients were having massive hemoptysis at the time of pneumonectomy. Eight-rib thoracoplasty with suturing of the intercostal muscles to the bronchial stump was performed on all patients. In 2 patients a mass closure of hilar vessels and bronchus was used because of inability to individually close the vessels and bronchus due to ligneous scarring of the hilum. Antibiotic and antifungal irrigations into the operative area were used postoperatively. Chest tubes were left in place 6 to 8 weeks. All wounds healed primarily. Patients were alive without recurrent local infection or tumor at follow-up 3 to 13 years postoperatively. PMID- 8452430 TI - Cardiopulmonary bypass procedures in dialysis patients. AB - To determine the operative outcome of chronic renal failure patients, we retrospectively reviewed twenty-five consecutive adult patients with chronic renal failure dependent on maintenance hemodialysis (21) or peritoneal dialysis (3), who underwent cardiopulmonary bypass procedures over a five-year period in our institution. The operations included isolated coronary artery bypass grafting in 16 patients; aortic valve replacement in 3; aortic valve replacement plus mitral valve replacement in 1; aortic valve replacement, mitral valve replacement, and coronary artery bypass grafting in 2; aortic valve replacement and coronary artery bypass grafting in 1, mitral valve replacement and coronary artery bypass grafting in 1, and repair of a thoracoabdominal aortic aneurysm in 1 patient. Fourteen operations were elective, and 11 were urgent or emergent. The number of patients with good (> 0.50), fair (0.30 to 0.50), and poor (< 0.30) left ventricular ejection fractions were 13, 9, and 3, respectively. There were 0, 7, 7, and 11 patients in New York Heart Association functional classification I, II, III, and IV, respectively. All patients were dialyzed within 24 hours before operation. All but 3 patients were managed by immediate postoperative peritoneal dialysis via a Technoff catheter placed intraoperatively (18 patients) or via a preexisting Technoff catheter (4 patients). This was then switched to hemodialysis when clinical conditions stabilized. Univariate analysis of 22 preoperative and intraoperative variables, followed by a multivariate analysis with a stepwise logistic regression model, was performed using the 30-day or in hospital operative mortality as the dependent variable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452431 TI - Surgical experience with defibrillator implantation using nonthoracotomy leads. AB - Between October 10, 1989, and June 17, 1991, 109 patients with life-threatening ventricular arrhythmias received an implantable cardioverter-defibrillator at our institution. In 50 patients, nonthoracotomy lead systems consisting of a subcutaneous chest wall patch electrode near the cardiac apex and one (Cardiac Pacemakers, Inc: Endotak C) or two (Medtronic: Transvene) transvenous electrodes were tested. The mean ejection fraction was 0.44 +/- 0.15 with a range from 0.19 to 0.81. Twenty-four patients had a history of open heart operation. In 43 patients the nonthoracotomy lead system was implanted, whereas in 7 patients epicardial patch lead systems were required due to elevated defibrillation thresholds during nonthoracotomy lead testing. There was one perioperative death unrelated to the operative procedure (hydrocephalus internus). Hemorrhage from the subcutaneous patch pocket or the device pocket that required reintervention occurred in 4 patients. During a mean follow-up of 13 +/- 5 months (range, 4 to 26 months) no dislocation of an endocardial lead, insulation defect, or lead fracture has been observed. In 1 patient, the lead system had to be removed due to infection of the subcutaneous patch pocket. The cardiovascular survival rate was 98% at 12 and 18 months, and freedom from sudden cardiac death was 100% at 6 and 12 months. In conclusion, defibrillator implantation using nonthoracotomy lead systems is feasible with a success rate of 86%, and during short-term follow up no problems related to the lead system such as dislocation, fracture, or insulation defect have occurred. PMID- 8452432 TI - Calprotectin and complement activation during major operations with or without cardiopulmonary bypass. AB - Plasma concentrations of the granulocyte cell marker calprotectin were assessed during operation and 24 hours postoperatively in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass, abdominal aneurysmectomy with implantation of an aortic graft, or thoracotomy without implantation of synthetic material. The concentration of calprotectin increased significantly (p < 0.01) in all three groups. Ten of the 30 patients in the group undergoing cardiopulmonary bypass received methylprednisolone at the start of the operation. No difference in calprotectin concentration was seen between the two subgroups (p > 0.05). Plasma concentration of calprotectin was shown to increase rapidly in patients undergoing cardiopulmonary bypass and aneurysmectomy, in whom complement activation also took place. However, the calprotectin concentration increased slowly during the operation and the postoperative period in patients undergoing a thoracotomy, in whom complement was not activated. At wound closure the calprotectin concentration was significantly elevated in the cardiopulmonary bypass and aneurysmectomy groups compared with the thoracotomy group (p < 0.05). The calprotectin concentration remained elevated during the postoperative period in all three groups. Our results indicate that calprotectin may serve as a suitable cellular marker when the biocompatibility of artificial surfaces is studied. PMID- 8452433 TI - Effects of pressure and duration of hyperkalemic infusions on endothelial function. AB - Infusions of crystalloid hyperkalemic cardioplegic solutions (CHCSs) are known to impair endothelium-dependent coronary relaxation. This impairment might also be influenced by high perfusion pressure and duration of CHCS infusion. To verify this hypothesis, we designed experiments to study the influence of pressure and duration of CHCS infusion as modulating factors in CHCS-related endothelial impairment. Isolated hearts of Sprague-Dawley rats were studied in a Langendorff apparatus for coronary endothelial function. Hearts (n = 6) were exposed to four different CHCSs containing 12, 24, 40, or 100 mmol/L of potassium chloride (KCl). Endothelial and smooth muscle functions were respectively tested by infusion of 5 hydroxytryptamine (1 x 10(-6) mol/L) and sodium nitroprusside (1 x 10(-5) mol/L) before and after CHCS perfusion. In group I (n = 24), 37 degrees C CHCSs were perfused at 80 cm H2O of pressure for 30 minutes. In group II (n = 24), the same CHCSs were perfused at 160 cm H2O for 30 minutes. In group III (n = 18), CHCSs containing 24, 40, and 100 mmol/L of KCl were infused at 160 cm H2O for 10 minutes. In all groups, response to sodium nitroprusside was unaltered by CHCS infusion, indicating that smooth muscle function was preserved. However, in group II, 5-hydroxytryptamine-induced vasodilation was significantly impaired in hearts perfused with CHCS containing 24 mmol/L of KCl or more, suggesting endothelial damage. This study demonstrates that, in addition to KCl concentration, pressure and duration of infusion are two major determinants in CHCS-mediated endothelial damage. PMID- 8452434 TI - Paranasal sinusitis: cryptic sepsis after coronary artery bypass operations. AB - Infections occurred in 52 of 400 patients (13%) undergoing coronary artery bypass operations from January 1987 to December 1990. The hospital courses of 5 patients (1.3%) in whom occult infections of the paranasal sinuses developed were reviewed. Only 1 patient had specific clinical findings of acute sinusitis (purulent nasal discharge). Computed tomography showed wall thickening, opacification, or air-fluid levels in one or more paranasal sinuses in each patient. All patients were successfully treated with surgical drainage and antibiotics. Risk factors for development of postoperative acute sinusitis include: prolonged tracheal intubation, airway colonization with nosocomial bacteria, inability to clear nasal secretions, sinus ostial obstruction, and critical organ system dysfunction. Physical examination and roentgenographic evaluation of the paranasal sinuses should be considered when postoperative sepsis of obscure etiology occurs. PMID- 8452435 TI - Influence of temperature of flushing solution on lung preservation. AB - For lung transplantation the technique of flushing the donor pulmonary vascular bed may provide advantages in lung preservation such as rapid cooling and washout of blood. However, rapid cooling of the ischemic lung may also produce adverse effects. The aim of this study was to compare methods of cold flushing and topical cooling, and to evaluate the effect of temperature of the flushing solution on lung preservation. A total of 25 rabbit lungs were studied. Using an ex vivo rabbit lung model, postischemic function was assessed by the ability of the lung to oxygenate perfused blood and by measurement of pulmonary artery and airway pressures. The lungs in group I were preserved with simple immersion at 10 degrees C for 30 hours. The lungs in groups II through V were flushed with solution containing phosphate-buffered dextran (LPD) at different temperatures (groups II and IV, 10 degrees C; groups III and V, 23 degrees C) and stored at 10 degrees C for various ischemic periods (groups II and III, 30 hours; groups IV and V, 36 hours). Pulmonary vascular resistance during flushing at 10 degrees C was significantly higher than that at 23 degrees C (p < 0.001). Flushing resulted in better preservation than topical hypothermia. Flushing at 23 degrees C resulted in superior postischemic function compared with flushing at 10 degrees C. We conclude that in lung preservation, uniform flushing with LPD solution improves the ischemic tolerance as compared with topical hypothermia, and that flushing with solutions at too low temperatures may have adverse effects on lung preservation. PMID- 8452436 TI - Male donor into female recipient increases the risk of pediatric heart allograft rejection. AB - Sixty-one infants and children, 12 years old or younger, who received an orthotopic cardiac allograft between November 1985 and December 1989 were analyzed for the incidence of rejection. Rejection was diagnosed non-invasively within the first 3 months and during the first year. Rejection episodes were diagnosed by signs and symptoms according to previously reported criteria. Multiple regression analysis with recipient age, donor age, donor-recipient weight ratio, number of HLA mismatches, sex of the recipient, sex-encoded minor tissue antigen incompatibility (H-Y: female recipients receiving male donor organ), graft ischemic time, lowest cyclosporine level during the first 2 postoperative weeks, and prophylactic use of OKT3 showed that H-Y was the only significant contributing factor for rejection at 3 months and 1 year (r = 0.308, p < 0.02; r = 0.308, p < 0.02; respectively). Patients were divided into two groups: group 1, 45 patients who were H-Y compatible (male and female recipients receiving female donor hearts); and group 2, 16 patients who were H-Y incompatible (female recipients with male hearts). Patients in group 2 had significantly more episodes of graft rejection than did patients in group 1 by 3 months and by 12 months after heart transplantation (3 months: 2.75 +/- 1.48 versus 1.67 +/- 1.41, p < 0.05; 1 year: 4.80 +/- 1.87 versus 2.59 +/- 1.93, p < 0.01; respectively). There were six grafts lost due to rejection in group 2 (6/15, 37.5%) and 7 grafts lost (7/45, 15.5%) in Group 1 (not significant). Heart transplantation with H-Y incompatibility resulted in a significantly greater incidence of rejection episodes. PMID- 8452437 TI - Severe ischemic left ventricular failure: coronary operation or heart transplantation? AB - Severe left ventricular failure in ischemic heart disease may contraindicate conservative surgical procedures. To redefine therapeutic indications, the clinical and angiographic data of 143 patients (137 men and 6 women) with ischemic heart disease and a left ventricular ejection fraction less than 0.30 who were seen by us between June 1985 and December 1990 were retrospectively analyzed. Patients were divided into three groups according to therapy: medical only, 72 (group 1); myocardial revascularization, 20 (group 2); and heart transplantation, 51 (group 3). Clinical status was poorer in group 3, with congestive heart failure as predominant symptom; angina was more frequent in group 2. No difference was noted in hemodynamic variables. Four early deaths (20.0%) occurred in group 2 and 7 (13.7%) in group 3. Follow-up ranged from 1 to 64 months (mean, 22 +/- 19 months), with an actuarial survival of 28% +/- 9%, 80% +/- 8% and 82% +/- 5% at 5 years in groups 1, 2, and 3, respectively. Even though postoperative New York Heart Association class was better in group 3 (1.0 versus 2.3 in group 2; p < 0.01), the difference in survival was not significant. Although in patients with ischemic heart disease and low left ventricular ejection fraction heart transplantation offers the best clinical results, considering the donor shortage, we conclude that myocardial revascularization may still be performed with good midterm results. PMID- 8452438 TI - Cardiopulmonary bypass and pulmonary thromboxane generation. AB - Sporadic cases of inexplicable noncardiogenic pulmonary edema occur after operations requiring total cardiopulmonary bypass (CPB). Prostaglandins, such as thromboxane (Tx) A2, have been implicated in this form of pulmonary pathology in many clinical and experimental settings. Because Tx generation has been demonstrated in association with ischemia of solid organs, we postulated that total CPB, which decreases pulmonary tissue perfusion and oxygenation, would stimulate local Tx synthesis. Total CPB was examined in 7 sheep. The level of TxB2 (a stable metabolite of the active, unstable A2) was measured in the left and right atria before, during, and after 105 minutes of total CPB. Significant increases in TxB2 concentrations occurred in the left atrium compared with the right (p < 0.05) during CPB. Immediately after reperfusion, both the left atrial and right atrial TxB2 concentrations increased significantly over the baseline values (p < 0.05), but this increase and the atrial gradient were rapidly abolished with continued pulmonary perfusion. To determine the effect of extracorporeal circulation without significant (< 30%) alteration in pulmonary perfusion, we evaluated the effect of partial CPB in 5 sheep. Increased TxB2 concentrations were noted at 15 and 30 minutes after the onset of partial CPB (left atrium increased significantly over baseline; p < 0.05), but this elevation spontaneously diminished to insignificance after 15 and 30 additional minutes of extracorporeal circulation. These data establish that total CPB stimulates Tx generation in the lung, and although the effect of partial CPB is transient, that of total CPB is progressive and abolished by reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452439 TI - Cavopulmonary connection in repair of atrioventricular septal defect with small right ventricle. AB - Between February 1991 and May 1992, 9 patients with a nonrestrictive inlet ventricular septal defect or complete atrioventricular septal defect and hypoplasia of the right ventricle underwent successful two-ventricle correction incorporating a bidirectional cavopulmonary anastomosis. Despite a satisfactory early postoperative course, large serous pleural effusions developed in 5 of them between 2 and 6 weeks after operation. Serial echocardiography showed an evolution of flow patterns in the superior vena cava from marked systolic reversal immediately after operation to nearly continuous forward flow into both pulmonary arteries about 6 weeks later. This pattern was consistent with the transition from cardiac-dependent to respiratory-dependent caval flow. The development of pleural effusions appeared to coincide with the loss of systolic caval flow reversal and resolved after establishment of a predominantly respiratory-dependent flow pattern. PMID- 8452440 TI - Biomechanical study of sternal closure techniques. AB - Median sternotomy is the most commonly used incision in cardiothoracic surgery. Closure of this incision is usually performed with parasternal wires, but alternate techniques have been proposed to improve closure stability. This study compares biomechanical stability of standard wire (No. 5 stainless steel) with that of three types of band closure: 5-mm Mersilene ribbon, 5-mm stainless steel band, and 5-mm plastic band. Eight bisected cadaver sterna were reapproximated using each method of sternal fixation and tested for biomechanical stability using an MTS Bionix 858 Biomechanical Tester. Loads of 50, 100, 150, and 200 Newtons (1 Newton = 1 kg.m/s2) were applied as a distracting force across the closure. A linear regression line of displacement as a function of increasing load was determined for each closure method; the slope of this line is inversely proportional to fixation stability. Displacement and load correlated linearly for each closure (r = 0.99). Mean slopes were 0.012 mm/Newton (95% confidence limits, 0.0098 to 0.0142 mm/Newton) for No. 5 stainless steel wire, 0.014 mm/Newton (95% confidence limits, 0.0118 to 0.0162 mm/Newton) for plastic band, 0.017 mm/Newton (95% confidence limits, 0.0148 to 0.0192 mm/Newton) for Mersilene ribbon, and 0.017 mm/Newton (95% confidence limits, 0.0148 to 0.0192 mm/Newton) for 5-mm steel band. No. 5 stainless steel wire provided the most stable closure, although statistical significance was achieved only in comparison with Mersilene ribbon and stainless steel band (p < 0.05). The superior stability of stainless steel wire closure may be due to tightening of the wires by twisting, which results in more tension across the reapproximated sternal halves than with other methods. PMID- 8452441 TI - Pulmonary artery balloon counterpulsation: safe after peripheral placement. AB - Pulmonary artery balloon counterpulsation is a promising experimental technique for treatment of right ventricular failure. However, clinical application has been limited in that the only device presently available (the large-volume intraaortic balloon) must be placed within a synthetic graft. Because a balloon with a smaller volume (which could be placed through a peripheral vein and be contained entirely within the pulmonary artery) would make the technique feasible on a wider scale, we tested an 8-mL pulmonary artery balloon placed through the femoral vein in 12 dogs. Two groups of animals were compared. One group had the pulmonary artery balloon in place but not counterpulsating; the other had the pulmonary artery balloon in place and counterpulsating. Each group was studied for 12 hours. A variety of hemodynamic parameters were measured. Effective diastolic augmentation and systolic unloading were noted in all 6 dogs that underwent counterpulsation (5.0 +/- 1.1 mm Hg of diastolic augmentation and 9.5 +/- 1.6 mm Hg of systolic unloading). Pulmonary function, as measured by arterial blood gas sampling and pulmonary vascular resistance, was not impaired. Examination of the heart and lungs showed no detrimental pathologic effects of pulmonary artery balloon counterpulsation. Placement of the balloon through a peripheral vein with a guidewire was easy and uncomplicated. We conclude that pulmonary artery balloon counterpulsation is safe over an extended period of 12 hours in the canine model and that diastolic augmentation and systolic unloading can be produced. PMID- 8452442 TI - Age and protection of the ischemic myocardium: is alkaline cardioplegia appropriate? AB - Hypothermic alkaline pharmacologic cardioplegia used in pediatric cardiac surgery may be less than satisfactory despite its benefits in adults. We determined whether the pH (7.8) of standard St. Thomas' II cardioplegic solution contributes to inadequate protection of the ischemic immature heart and whether the effect is age-related. Modified hypothermic St. Thomas' II solution (pH range, 4.8 to 8.8) was compared with hypothermic bicarbonate buffer alone (pH 7.25) in protecting the ischemic immature (7 to 10 days old) and mature (12 months old) rabbit heart. Isolated hearts (n = 6 per group) were perfused with bicarbonate buffer, and aortic flow was measured before hypothermic (14 degrees C) ischemia (immature hearts: 4 hours; mature hearts: 3 hours). Hearts were reperfused, and enzyme leakage and recovery of function were measured. In the immature heart, a bell shaped dose-response profile was observed for pH and recovery of aortic flow but not for postischemic creatine kinase leakage. Optimal recovery of aortic flow (98% +/- 3%) occurred at pH 6.8, which was greater than protection with hypothermia alone (82% +/- 4%; p < 0.05) and standard St. Thomas' II solution (72% +/- 2%; p < 0.05). In the mature heart, a bell-shaped dose-response curve existed for recovery of aortic flow and a U-shaped curve existed for creatine kinase leakage. Again, optimal recovery of aortic flow (84% +/- 5%), which was superior to that with standard St. Thomas' II solution (60% +/- 8%; p < 0.05), and minimal enzyme leakage also occurred at pH 6.8, as did the least enzyme leakage (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452443 TI - Delayed myocardial laceration after intrapericardial pneumonectomy. AB - Curative resection for large central bronchogenic tumors may require radical or intrapericardial pneumonectomy. Myocardial herniation through the pericardial defect is a rare early postoperative complication. Prevention of cardiac herniation and subsequent hemodynamic compromise is always necessary after intrapericardial pneumonectomy. PMID- 8452444 TI - Long-term follow-up and resection of a postoperative false aortic aneurysm. AB - This report describes the course and operative findings in a 66-year-old man with a densely calcified false aneurysm of his ascending aorta 19 years after replacement of a severely stenosed bicuspid aortic valve with a McGovern-Chromie prosthesis. This report emphasizes the need to consider this possibility, even in patients with a very remote prior operation. PMID- 8452445 TI - Traumatic sinus of Valsalva fistula and aortic valve rupture. AB - A rare case of nonpenetrating trauma-induced fistula from the right sinus of Valsalva to the right atrium and aortic cusp disruption is reported. The trauma occurred 2 1/2 years previously. The fistula was closed with a Dacron patch, and the cusp tear was sutured. PMID- 8452446 TI - Successful repair of combined ventricular septal rupture and free wall rupture. AB - The successful surgical repair of combined ventricular septal perforation and free wall rupture (double rupture) after inferior myocardial infarction is reported. Extensive inferior wall infarctectomy was performed, and both defects were closed with a prosthetic patch, using a modification of the technique developed by Daggett. The patient was alive and well 1 year after operation. PMID- 8452447 TI - Ventricular septal defect creation for relief of tunnel subvalvular aortic stenosis. AB - In infants, the management of severe tunnel subvalvular aortic stenosis associated with hypoplastic aortic annulus remains a major surgical challenge. We report a case of such lesion treated by rerouting the systemic blood flow through a created subpulmonary ventricular septal defect toward the right ventricular outflow tract and the pulmonary valve. This technique provided complete relief of the left ventricular outflow tract obstruction without the implantation of a systemic prosthetic valve. PMID- 8452448 TI - Intraoperative transthoracic ultrasonographic localization of occult lung lesions. AB - During video-assisted thoracoscopic operations, identification of small peripheral lung nodules can be challenging. We report the use of intraoperative intrathoracic ultrasonography for localization of lung tumors before resection in 2 patients. PMID- 8452449 TI - Management of patent saphenous vein grafts during reoperative coronary artery bypass grafting. AB - A patient was referred for coronary artery bypass reoperation. After a left internal mammary artery was grafted to the left anterior descending coronary artery, the diseased but patent old saphenous vein graft was ligated. This resulted in severe myocardial failure, which was corrected only after restoration of flow through the old vein graft. We suggest the decision to ligate or replace an old vein graft should be individualized to avoid the risk of myocardial ischemia. PMID- 8452450 TI - Thoracoscopic transdiaphragmatic approach for adrenal biopsy. AB - The role of thoracoscopy for the management of intrathoracic diseases has expanded with advancement in endoscopic instrumentation and technology. We report a case of thoracoscopic transdiaphragmatic biopsy of an adrenal gland for metastatic carcinoma. The procedure was uncomplicated and the patient was discharged on the second postoperative day. The morbidity of traditional approaches for adrenal operation was avoided. Thoracoscopy may be a useful approach in selected patients for adrenal operation. PMID- 8452451 TI - Infected hepatic Echinococcus cyst presenting as recurrent Escherichia coli empyema. AB - An 81-year-old man, previously a shepherd in Italy, presented with recurrent Escherichia coli empyema over an 8-month period. His empyema was caused by an infected, nonviable hepatic Echinococcus cyst that eroded the diaphragm and led to intermittent spillage and pleural seeding. This case demonstrates that when dealing with Escherichia coli empyema, a subdiaphragmatic source ought to be suspected, and among immigrants from areas with prevalent hydatid disease, infected hepatic Echinococcus cyst might rarely be the cause. PMID- 8452452 TI - Successful combined operation for mitral stenosis and atrial fibrillation. AB - Simultaneous surgical treatment of mitral stenosis and atrial fibrillation was performed. The patient's postoperative course was uneventful, the rhythm changed to sinus rhythm, and the patient was discharged on the 21st postoperative day in stable condition. PMID- 8452453 TI - Technique of transplantation for hypoplastic left heart syndrome with left superior vena cava. AB - The presence of a left superior vena cava in infants with hypoplastic left heart syndrome complicates the technical performance of orthotopic cardiac transplantation. In this report we describe a modification of the recipient cardiectomy to maintain patency of the left superior vena cava, leaving the recipient coronary sinus as a conduit for it into the right atrium and avoiding complex venous reconstructions. PMID- 8452454 TI - Localized supravalvar aortic stenosis: a new technique for repair. AB - The deformity in supravalvar aortic stenosis includes generalized thickening of the tissues of the aortic root with a fairly normal sized aortic valve ring. The thickened tissues may obstruct the origins of the left and right coronary arteries. We have repaired 2 cases with complete excision of the stenosing ring below the level of the commissures of the aortic valve into the sinuses, to the level of the left and right coronary arteries. PMID- 8452455 TI - Transseptal insertion of left atrial line: a simple and safe technique. AB - The widespread use of left atrial lines underscores the importance of left atrial pressure monitoring in open heart operations. We present a simple and safe method of intraoperative insertion of a left atrial line during an open heart operation. Foremost among the several advantages of this method is that there would no longer be any concern of postoperative bleeding after removal of the left atrial line. PMID- 8452456 TI - Subclavian artery cannulation for infant extracorporeal membrane oxygenation. AB - A technique is presented for subclavian artery cannulation for extracorporeal membrane oxygenation. This method allows antegrade perfusion of the carotid artery to occur both during extracorporeal membrane oxygenation and after decannulation. This method may prevent neurologic sequelae associated with the more common techniques using the carotid artery. PMID- 8452457 TI - Quantum leap forward in the management of cardiac trauma: the pioneering work of Dwight E. Harken. PMID- 8452458 TI - Technical advances in the treatment of left ventricular aneurysm. AB - The resulting abnormal geometry after surgical treatment of left ventricular aneurysm has concerned a number of surgeons since the first successful repair in 1958, but little attention was placed on the altered geometry until attempts were made to effect a more physiologic aneurysmorrhaphy in 1973. Substantial attention was focused on a concept of geometric reconstruction from within the left ventricle in 1985. A prosthetic patch was employed with the concept to redirect normal muscle bundles to their original orientation and position. Further refinements include use of improved materials for the repair, preservation and bypass of the left anterior descending coronary artery, ablation of ventricular arrhythmias when indicated, and the absence of prosthetic material used in contact with the pericardial surface. Our experience with repair of 61 left ventricular aneurysms at West Jefferson Medical Center over a 4 1/2-year period with a 3.3% mortality rate has prompted a change from the standard linear repair to routine use of a modified endoventricular repair. Currently, the low surgical risk due to advances in left ventricular aneurysmorrhaphy combined with the knowledge that contractile areas will progressively deteriorate in ventricles stressed by poor hemodynamics and with data showing improved left ventricular function postoperatively have led to more liberal recommendations for early left ventricular aneurysm repair. PMID- 8452459 TI - Selection of cardial valvular prostheses. PMID- 8452460 TI - 1992: Effect of internal mammary artery dissection on sternal vascularization. 1993 update. PMID- 8452461 TI - Venting and deairing without a roller pump. PMID- 8452462 TI - Measurement of instantaneous pulmonary capillary blood flow. PMID- 8452463 TI - Surgical management of spontaneous pneumothorax in patients with AIDS. PMID- 8452464 TI - Heparin-induced thrombocytopenia. PMID- 8452465 TI - Lung cancer in the young. PMID- 8452466 TI - Cervical esophageal anastomosis. PMID- 8452467 TI - Thoracoscopy and spontaneous pneumothorax. PMID- 8452468 TI - Transplantation using donor hearts from patients with circulatory arrest. PMID- 8452469 TI - Beneficial effect of nicardipine on perioperative myocardial ischemia. PMID- 8452470 TI - Open lung biopsy. PMID- 8452471 TI - [Bone injuries in gunshot wounds of the neck]. AB - Some typical bone injuries by shots to the back of the neck are reported. Significant Findings in skeletal remains could be detected even after two decades. PMID- 8452472 TI - [Postmortem diagnosis of exogenous insulin administration]. AB - Toxicological analyses are presented in connection with the decrease of a 51-year old female medical practitioner. The woman was found dead in a woodland about 250 metres far from her motor car. According to her relatives the woman had expressed her intention to commit suicide. Two single use syringes, two empty (300 units) cartridges intermediate type human insulin, and one empty ampoule of 10 mg diazepam were found near the corpse. The toxicological analyses of the heart blood resulted in 210 ng diazepam/ml, 382 mu units/ml insulin and 0.58 ng/ml C peptide. After extraction of a tissue sample from the injection area (cubital region) 113 milliunits insulin could be detected by radioimmunoassay. The insulin concentration in relation to the C-peptide concentration in the blood of the corpse indicated an exogenous supply of insulin. The HbA1c and fructosamine data in the blood and the histological examination of the pancreas showed that the woman had not suffered from diabetes. PMID- 8452473 TI - [Sex determination in forensic odontostomatology. Methodologic revision and new procedures]. AB - First of all, authors review methods used for sex determination in the forensic odontostomatology. Than they describe those more recent with special regard to the evaluation of the mandibular-canine-index (MCI). In their opinion this technique gives apparently encouraging preliminary results. They have to be confirmed by several controls in relation to operative potentiality available in their country and to the characteristics of italian population. PMID- 8452474 TI - Thalidomide derivatives and the immune system. I. Changes in the pattern of integrin receptors and other surface markers on T lymphocyte subpopulations of marmoset blood. AB - Treatment of marmosets (Callithrix jacchus) with thalidomide (Thd) or its derivative EM12 (which is also teratogenic, but more stable to hydrolysis) resulted in the lack of reaction of adhesion surface receptors (integrins) on T lymphocytes in venous blood. Lymphocyte subsets appeared, for example CD4+CD2-, which are not found under normal conditions. (a) There was no clear effect of the treatments on the total number of leukocytes or lymphocytes or on the total number of CD4+ or CD8+ T lymphocytes. (b) A decrease in the percentage of the cytotoxic T cells carrying the CDw29 marker (CD8+CD56+CDw29+) at a dose as low as 5 mg EM12/kg bw, and an increase in the percentage of suppressor cells carrying the CDw29 marker (CD8+CD56-CDw29+) at 10 mg EM12/kg bw were found. Similar effects were induced by Thd at somewhat higher doses, while supidimide (Sup) was less active even at the very high dose of 100 mg/kg bw. Especially at the lower doses these effects occurred with a lag phase and persisted after discontinuation of the dosing. Alterations induced in helper T cell subpopulations by Thd or EM12 were less impressive (no significant effect was observed with 5 mg EM12/kg bw). Some changes were observed at higher dose levels in the CD4+CD45RA+CDw29+ cells and the CD4+CD45RACDw29+ cells. (c) The most significant effect, reduction in the reactivity of CD2+, was detectable subsequent to daily oral doses as low as 10 mg Thd/kg or 1 mg EM12/kg bw. Peak plasma concentrations to be expected under these experimental conditions are less than 1 micrograms/ml. (d) The surface receptors found to be affected include among others: CD2 (LFA-2) and CD11a (LFA-1 alpha) and CD18 (LFA-1 beta). Clearly, CD4+ cells were found to be more susceptible to the loss of the integrin receptors than CD8+ cells. (e) The effect persisted for several weeks subsequent to the discontinuation of the dosing. (f) A rough estimate of the relative potency to reduce the CD2 receptor in the marmoset suggests EM12 to be five to ten times more potent than Thd. Sup, a Thd derivative reported to exhibit no or a low teratogenic potency, was found to be at least five times less potent than Thd. (g) The alterations of surface adhesion receptors by the substances studied in this investigation were not confined to T lymphocytes. We also observed similar effects on B lymphocytes, monocytes, and neutrophils, and many other cell types carrying such receptors might be affected.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8452475 TI - In vitro kinetics of styrene and styrene oxide metabolism in rat, mouse, and human. AB - Styrene oxide (SO), a labile metabolite of styrene, is generally accepted as being responsible for any genotoxicity associated with styrene. To better define the hazard associated with styrene, the activity of the enzymes involved in the formation (monooxygenase) and destruction of SO (epoxide hydrolase and glutathione-S-transferase) were measured in the liver and lungs from naive and styrene-exposed male Sprague-Dawley rats and B6C3F1 mice (three daily 6-h inhalation exposures at up to 600 ppm styrene) and Fischer 344 rats (four daily 6 h inhalation exposures at up to 1000 ppm styrene), and in samples of human liver tissue. Additionally, the time course of styrene and SO in the blood was measured following oral administration of 500 mg styrene/kg body weight to naive Fischer rats and rats previously exposed to 1000 ppm styrene. The affinity of hepatic monooxygenase for styrene, as measured by the Michaelis constant (Km), was similar in the rat, mouse, and human. Based on the Vmax for monooxygenase activity and the relative liver and body size, the mouse had the greatest capacity and humans the lowest capacity to form SO from styrene. In contrast, human epoxide hydrolase and a greater affinity (i.e., lower Km) for SO than epoxide hydrolase from rats or mice while the apparent Vmax for epoxide hydrolase was similar in the rat, mouse, and human liver. However, the activity of epoxide hydrolase relative to monooxygenase activity was much greater in the human than in the rodent liver. Hepatic glutathione-S-transferase activity, as indicated by the Vmax, was 6- to 33-fold higher than epoxide hydrolase activity. However, the significance of the high glutathione-S-transferase activity is unknown because hydrolysis, rather than conjugation, is the primary pathway for SO detoxification in vivo. Human hepatic glutathione-S-transferase activity was extremely variable between individual human livers and much lower than in rat or mouse liver. Prior exposure to styrene had no effect on monooxygenase activity or on blood styrene levels in rats given a large oral dose of styrene. In contrast, prior exposure to styrene increased hepatic epoxide hydrolase activity 1.6-fold and resulted in lower (0.1 > P > 0.05) blood SO levels in rats given a large oral dose of styrene. Qualitatively, these data indicate that the mouse has the greatest capacity and the human the lowest capacity to form SO. In addition, human liver should be more effective than rodent liver in hydrolyzing low levels of SO.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8452476 TI - Monitoring of exposure to styrene oxide by GC-MS analysis of phenylhydroxyethyl esters in hemoglobin. AB - Styrene oxide, which is the genotoxically active metabolite of styrene, reacts in vivo with carboxylic acid residues in hemoglobin forming phenylhydroxyethyl esters. Mild alkali hydrolysis cleaves these ester adducts, yielding styrene glycol, which in human blood labelled in vitro with 14C-styrene oxide accounted for 15% of the total radioactivity covalently bound to the protein. A quantitative assay procedure has been developed for measuring the base released styrene glycol in globin. The method utilizes solvent extraction followed by trimethylsilyl ether derivatization and separation and quantitation by capillary gas chromatography with selective ion recording mass spectrometry. Globin labelled in vitro with d8-styrene oxide was used as the internal standard. The method was used to establish a dose-response relationship in rats given single i.p. doses of styrene oxide (83.3-833 mumol/kg body wt). The method, which allows quantitation of the adducts down to levels of 15 pmol/g globin, has the potential to act as a dosimeter for industrial workers exposed to styrene or styrene oxide. PMID- 8452477 TI - Evaluation of DNA damage by alkaline elution technique after inhalation exposure of rats and mice to 1,3-butadiene. AB - The alkaline filter elution technique was used to evaluate single strand breaks (SSB), DNA-DNA (DDCL) and DNA-protein cross-links (DPCL) in liver and lung of male rats (Sprague-Dawley) and male mice (B6C3F1) after exposure to 2000 ppm 1,3 butadiene (BD) for 7 days (7 h/day and/or to 100, 250, 500, 1000) 2000 ppm BD for 7 h. SSB were detected in liver DNA of both species at 2000 ppm. Cross-links are more pronounced in mouse lung than in mouse liver. Elution rates of lung DNA from mice exposed for 7 h to different concentrations of BD revealed an increase in cross-links between 250 and 500 ppm, and a further increase in cross-links up to 2000 ppm. No such signs of genotoxicity could be observed for the lung of rats. Our data support the involvement of reactive metabolites (epoxybutene and especially diepoxybutane) in butadiene-induced carcinogenesis in the mouse but not to that extent in the rat. PMID- 8452478 TI - In vivo metabolism of retrorsine and retrorsine-N-oxide. AB - The in vivo metabolism and excretion of the urinary metabolites from the pyrrolizidine alkaloids (PAs), retrorsine (RET) and retrorsine-N-oxide (RET-NO) have been studied in rats. Isatinecic acid (INA), pyrrolic metabolites, N-oxides and retronecine accounted for 31.0, 10.3, 10.8 and 0.39% of the administered RET. Predosing rats with triorthocresyl phosphate (TOCP), had no effect on the excretion of pyrrolic metabolites and INA. Phenobarbital (PB) increased the excretion of both pyrrolic metabolites and INA with a corresponding decrease in the excretion of RET and N-oxides; the retronecine levels remained unaltered. When RET-NO was administered i.p., the urinary levels of pyrrolic metabolites, INA and RET were decreased relative to those treated with RET. The p.o. administration of RET-NO produced significantly higher levels of pyrrolic metabolites, INA and RET. These results suggest that esterase hydrolysis plays a minor role in the formation of INA and that a common metabolic pathway may exist between pyrrolic metabolites and INA formation. PMID- 8452479 TI - Fate of fluazifop butyl in rat and human skin in vitro. AB - Enzyme mediated hydrolysis of fluazifop butyl has been measured with rat and human skin post-mitochondrial fractions. Rat skin had a ten times greater capacity to metabolise fluazifop butyl than human skin, but the enzyme affinities were similar. The post-mitochondrial fraction metabolism was compared to that seen during absorption in a flow through diffusion cell with viable skin. Limited hydrolysis of absorbed fluazifop butyl was seen in rat skin, but increased two fold if the stratum corneum was removed. The stratum corneum was found to retain fluazifop butyl. When the skin was pre-incubated with the esterase inhibitor bis (p-nitrophenol) phosphate (BNPP), reduced metabolism was seen. No metabolism of fluazifop butyl was seen in human skin during absorption. Retention of the compound by the stratum corneum is postulated to restrict the accessibility of the compound to the enzyme site, thus influencing the observed metabolism during the absorption process. PMID- 8452480 TI - Tamoxifen induces hepatocellular carcinoma in rat liver: a 1-year study with two antiestrogens. AB - The effects of equimolar doses of the triphenylethylene antiestrogens tamoxifen and toremifene on female Sprague-Dawley rat liver were studied in a 52-week toxicity study which included a 13-week recovery period. Liver tumors were found in four out of five rats at the highest dose level of tamoxifen (45 mg/kg per day) after 52 weeks of dosing, and these appeared to be hepatocellular carcinomas in three rats. After the 13-week recovery period all surviving rats in the highest tamoxifen dose group had large liver tumors (diameter up to 2 cm) which appeared to be hepatocellular carcinomas in five out of six rats. No tumor was observed in the toremifene-treated rats (48 mg/kg per day) either after 52 weeks of dosing or after the recovery period. Electron microscopic morphometric analysis after 52 weeks of dosing revealed that at the tamoxifen high dose level, the volume densities of the peroxisomes, mitochondria, and residual bodies were elevated in the nonneoplastic hepatocytes of the rats. In the neoplastic hepatocytes of the tamoxifen-treated rats the volume density of nuclei was slightly elevated. The slight proliferation of peroxisomes and mitochondria might be related to tumor development in the tamoxifen treated rats. PMID- 8452481 TI - Acute inhalation toxicity of high concentrations of silane in male ICR mice. AB - In order to examine the toxicity of silane, male ICR mice were exposed to silane for 30 min (n = 8), 1 or 4 h (n = 12) at concentrations of 2500, 5000, 7500 (30 min experiment only) or 10,000 ppm. In the 1- and 4-h experiments, 12 mice were divided into two sub-groups: four for 2-day observation and eight for 2-week observation. The mortality was six deaths out of eight mice exposed to 10,000 ppm for 4 h. No deaths occurred in any of the other experiments. In the mice sacrificed 2 days after the exposure, acute renal tubular necrosis was observed at 10,000 ppm (1-h exposure) or at 2500 ppm or more (4-h exposure). Reduction in body weight, increase in relative kidney weight and blood urea nitrogen (BUN) level, and splenic atrophy and inflammatory changes of the nasal mucosa were also seen in the 10,000 ppm-4 h exposure group. In the mice sacrificed 2 weeks after the exposure, tubulo-interstitial nephritis (TIN) developed at 7500 ppm or more (30-min exposure) or at 5000 ppm or more (1- and 4-h exposure). BUN increased in a dose-dependent manner, and BUN in TIN positive mice was significantly higher than that in TIN negative mice (1- and 4-h exposure). No histopathological changes were observed in the glomeruli. These results indicate that the LC50 of silane in mice is between 5000 and 10,000 ppm for 4-h exposure and is greater than 10,000 ppm for 1-h or 30-min exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452482 TI - Metallothionein in isolated pancreatic islets of mice: induction by zinc and streptozotocin, a naturally occurring diabetogen. AB - Metallothionein (MT) concentrations were determined in the cytosol of isolated pancreatic islets of mice, using both the cadmium (Cd)-heme and the Cd-Chelex assay. Both constitutive MT levels and significant MT induction were detected in islet cells. For MT induction, mice were injected intraperitoneally (i.p.) with either zinc sulfate (Zn) or the diabetogen streptozotocin (STZ). Following an i.p. injection of 15 mg Zn.kg-1 body weight (body wt), the mean index of MT induction found in islets was comparable to that found in liver tissue, which was used as control. After i.p. injection of 30 mg Zn.kg-1 or a single high dose of STZ (100 or 200 mg.kg-1), the indices of MT induction in islets exceeded those in liver by a factor of 1.3, 2.5, or 1.5. After multiple low doses of STZ (3 or 5 x 40 mg.kg-1 given on consecutive days), in contrast, the MT induction indices in islets exceeded those in liver by a factor of 3.5 and 3.9 for 3 x 40 respectively 5 x 40 mg STZ.kg-1. In conclusion, our results demonstrate constitutive MT levels in isolated pancreatic islets and significant MT induction after i.p. injection with Zn or STZ, in particular after repeated low doses of STZ. PMID- 8452484 TI - O,O,S-Trimethyl phosphorothioate induces hypothermia in Fischer 344 rats in a manner dependent on both doses and housing temperatures. AB - We explored the effects of O,O,S-trimethyl phosphorothioate (OOS-TMP) on body temperatures in Fischer 344 female rats. The 7-day LD50 p.o. for Fischer 344 female rats was found to be 11.8 mg/kg. OOS-TMP induced long-lasting (more than 48 h) and extensive hypothermia at doses > or = 14 mg/kg at a typical laboratory temperature (22 degrees C) while it produced typical symptoms at 10 mg/kg without hypothermia. In contrast, pair-fed (to 20 mg/kg rats) rats (n = 4) did not become hypothermic, negating any role of hypophagia in OOS-TMP associated hypothermia. We next investigated the effects of housing temperatures on toxicities at a LD50 dose (12 mg/kg). At 30 degrees C (n = 11) and 22 degrees C (n = 13), rats did not have hypothermic bouts but at 15 degrees C, eight out of ten rats had. Evidence that changes of housing temperatures neither modified clinical symptoms nor changed mortality rates discards a possibility of hypothermia being involved in delayed toxicity. A novel result of the present study suggests that thermoregulation may be heavily impaired by a special class of organophosphorus compounds. PMID- 8452483 TI - Production and characterization of antibodies directed against organophosphorus nerve agent VX. AB - A strategy is described to raise high-affinity antibodies directed against the organophosphorus nerve agent VX [O-ethyl S-(2-diisopropylamino)ethyl)methyl phosponothionate]. Ten chemical derivatives of VX (haptens) have been synthesized. Their structures differ principally from VX structure by substitution of S-atom by an O-atom or CH2-group and by introduction of a reactive group (carboxylic acid, arylamine or primary amine) on the O-ethyl side chain. None of these haptens, except one, exhibit potential toxicity as tested by their inhability to inhibit acetylcholinesterase (E.C. 3.1.1.7.). After coupling with a protein carrier, they were injected intradermally to rabbits. Nine of these immunogenic conjugates led to the appearance of antibodies able to bind VX in a competitive solid phase immunoassay. The apparent titer and affinity of the antisera differed greatly depending on the hapten used. The highest affinity (9 nM) was observed with the VX derivative bearing O-S substitution and O-ethyl carboxylic side chains. The antibodies appear specific for VX, since cross reactivity with other nerve agents (Soman, Sarin or Tabun) was low. However, two haptens elicited antibodies with affinity to Soman or Sarin in the micromolar range. Antibodies were able to neutralize VX inhibition of acetylcholinesterase in vitro but not in vivo. PMID- 8452485 TI - On the toxicity of low doses of tetrasodium-ethylenediamine-tetraacetate (Na EDTA) in normal rat kidney (NRK) cells in culture. AB - The toxicity of tetrasodium-ethylenediaminetetraacetate (Na-EDTA) was investigated in normal rat kidney cells (NRK-52E, American Type Culture Collection) in culture. Cell death and reduced colony-forming ability were observed at Na-EDTA concentrations < 100 microM, that is at concentrations lower than that required to chelate all the Ca2+ in the growth medium. No toxicity was observed when cells were exposed to 100 microM Zn- or Fe-EDTA, but the same concentration of Cu-EDTA was as toxic as Na-EDTA. Continuous exposure of the cell cultures to 5 microM Na- or Zn-EDTA for up to 7 weeks yielded no indications of toxicity. PMID- 8452486 TI - Structure and development of bronchus-associated lymphoid tissue in conventionally reared broiler chickens. AB - The development of bronchus-associated lymphoid tissue (BALT) in conventionally reared broiler chickens of 1 day and 1, 2, 3, 4, 6, and 8 weeks of age was studied using light and electron microscopy (scanning and transmission). BALT in these chickens resembled other mucosa-associated lymphoid tissues (MALT) in that it was composed of an altered epithelium overlying a population of lymphocytes and contained potential antigen-presenting cells, such as macrophages and dendritic cells; high endothelial venules were also present. In contrast to other MALT, epithelial cells in chicken BALT were not of the M-cell type; i.e., they lacked large numbers of apical tubules and vesicles for specialized uptake of luminal antigens. There were age-related differences in size, number, and cellular composition of BALT nodules. Lymphoid nodules were progressively larger and more numerous with increasing age. Germinal centers were present in birds 2 weeks of age and older. BALT epithelium was primarily squamous and non-ciliated in 1-day and 1-week-old chicks, becoming progressively more columnar and ciliated in older chickens. Lymphocyte infiltration of the epithelium was extensive at 1 to 4 weeks of age; in older chickens, distinct epithelial and lymphocytic compartments were separated by connective tissue. PMID- 8452487 TI - Skeletal myopathy produced with experimental dosing of turkeys with monensin. AB - Monensin was given via gavage to 5- and 6-week-old broad-breasted white turkeys. The birds were allotted into four groups--three groups given monensin and one group of controls--in two experimental trials. Treated turkeys in Trial 1 received one dose of monensin per day for 4 days at 4.7 mg monensin/kg body weight, 8.8 mg/kg, or 17.6 mg/kg. Treated turkeys in Trial 2 received one dose of monensin per day for 5 days at 1.93 mg/kg, 4.7 mg/kg, or 8.8 mg/kg. Turkeys receiving the lowest dose showed no clinical signs of myopathy. Birds receiving 4.7 mg monensin/kg developed ataxia after the third dose and rear limb paresis and paralysis after the fifth dose. Turkeys receiving 8.8 mg/kg were ataxic after the second dose and paretic or paralyzed after the fourth dose. Turkeys receiving 17.6 mg/kg were ataxic 3 hours after the first dose and paretic or paralyzed 8 hours after the first dose. Histologically, a necrotizing skeletal myopathy was present in the muscles of the rear limbs. A dose-related response was observed in the percentage of myofibers damaged in birds that survived until the end of the trials. Intrafiber edema and vacuolation were observed in histologic sections from myocardium of turkeys from the two highest dose groups. PMID- 8452488 TI - Effects of different levels of oocyst inocula of Eimeria acervulina, E. tenella, and E. maxima on plasma constituents, packed cell volume, lesion scores, and performance in chickens. AB - The effects of different levels of oocyst inocula of Eimeria acervulina, E. tenella, or E. maxima on plasma carotenoids, total plasma lipids, total plasma proteins, packed cell volume (PCV), bird performance, and coccidial lesion scores were determined in male Hubbard chickens. Each test consisted of an uninfected treatment and either four levels (E. tenella and E. maxima) or five levels (E. acervulina) of inocula. Carotenoids and lipids were significantly (P < or = 0.05) depressed by E. acervulina starting at 10(2) oocysts per bird, whereas 10(4) and higher inoculum levels significantly depressed plasma protein. Carotenoids and lipids were significantly depressed by E. tenella beginning at 10(4) oocysts per bird, whereas 10(2) oocysts per bird and greater levels significantly depressed plasma protein. E. maxima significantly depressed carotenoids and lipids beginning at 6.7 x 10(2) oocysts per bird and plasma protein at 6.7 x 10(4) oocysts per bird. PCV was depressed by E. acervulina and E. tenella starting at 10(4) oocysts per bird but was not affected by E. maxima. Weight gain was significantly depressed by E. acervulina beginning at 10(5) oocysts per bird, by E. tenella at 10(4) oocysts per bird, and by E. maxima at 6.7 x 10(4) oocysts per bird. Coefficients of determination (R2) were highest for carotenoids (0.96 0.99), followed by lipids (0.93-0.96), weight gain (0.89-0.91), feed:weight gain ratio (0.89-0.91), and protein and PCV (0.65-0.92). Results demonstrated that plasma carotenoids and lipids were excellent response variables for measuring the effects on broiler chickens of each of the Eimeria spp. tested. PMID- 8452489 TI - Occurrence of Salmonella enteritidis in unpasteurized liquid egg in the United States. AB - In order to gain a greater understanding of the occurrence and distribution of Salmonella enteritidis in the United States, a survey of unpasteurized liquid egg (collected at 20 egg-breaking plants across the United States) was conducted over a 52-week period. Weekly liquid egg samples were submitted for Salmonella culturing at the National Veterinary Services Laboratories. Group D positive salmonellae were serotyped and phage-typed. On a regional basis, the Northern Region of the United States had the highest S. enteritidis recovery, with 20% of the samples submitted from plants in that region culture-positive for this serotype. Salmonella enteritidis positives from the Southeast, Central, and Western regions were 10%, 15%, and 6% of the samples submitted, respectively. PMID- 8452490 TI - Effect of prolonged administration of dietary capsaicin on Salmonella enteritidis infection in leghorn chicks. AB - The effect of 14 or 19 days of dietary capsaicin (18 ppm) on Salmonella enteritidis infection and histological, morphometric, and pH changes of the ceca was investigated. At day 13 or day 18, chicks were challenged with 10(8) colony forming units of S. enteritidis. Chicks were killed and cultured 24 hours later. The total number of S. enteritidis-organ-culture-positive chicks was significantly lower among chicks fed capsaicin for either 14 or 19 days than among controls (P < 0.05). Subjective histological examination revealed a mild to moderate infiltration of mononuclear cells and heterophils in lamina propria of ceca, as well as epithelial cell proliferation in chicks following either 14 or 19 days of capsaicin administration. Using morphometric analysis, the mean lamina propria thickness and mean epithelial cell thickness in chickens fed capsaicin for 14 or 19 days were significantly greater than in controls (P < 0.05). Capsaicin significantly decreased luminal pH in both trials (P < 0.05). These data indicate that the observed capsaicin-induced resistance to S. enteritidis organ invasion is associated with measurable pH and morphological changes of the cecal mucosa. PMID- 8452491 TI - Abrogation of age-related resistance to chicken infectious anemia by embryonal bursectomy. AB - Embryonally bursectomized (Ebx) chickens developed signs and lesions typical of chicken infectious anemia (CIA) when infected with CIA-1 isolate of chicken infectious anemia virus (CIAV) at 21 or 38 days of age. In both cases, the chickens had low hematocrit values after the 14th day of inoculation, and the percentage of CD4+ and CD8+ cells in the thymus was markedly reduced at 21 days postinoculation. Even though intact chickens became infected, they never developed low hematocrit values. The data support the hypothesis that age-related resistance to CIA is antibody-mediated and is not due to disappearance of the CIAV target cell; the data also suggest that CD4+/CD8+ cells are the target for infection. PMID- 8452492 TI - Immunoblots of outer-membrane proteins of chlamydiae with sera from turkeys experimentally exposed to avian and mammalian Chlamydia psittaci. AB - Outer-membrane protein (OMP)-enriched preparations from avian (turkey/TT3 and parrot/VS1) and mammalian (sheep abortion/B577) strains of Chlamydia psittaci were compared by immunoblotting using sera from turkeys exposed to these strains. Turkeys inoculated with avian chlamydiae became infected and developed strong serological responses, but turkeys inoculated with B577 failed to develop detectable serological responses. Sera from turkeys exposed to either of the two avian strains could be differentiated on the basis of immunoreaction patterns with OMPs of homologous and heterologous strains. Fewer bands and often weaker reactions were detected using sera from TT3- and VS1-inoculated birds with the heterologous avian strain. Sera from turkeys inoculated with either avian strain reacted with the 97,400-molecular weight (MW) protein. The sera reacted with the major outer-membrane protein (MOMP) of the homologous strains but not consistently with the MOMP of the heterologous strain. Results suggest that the 97,400-MW protein is highly immunogenic for turkeys and antigenically more complex than the MOMP. PMID- 8452493 TI - In situ hybridization for the detection of chicken anemia virus in formalin fixed, paraffin-embedded sections. AB - The development of a biotinylated in situ hybridization procedure for the detection of chicken anemia virus (CAV) is described. A double-stranded DNA probe was prepared using polymerase chain reaction and was biotinylated by nick translation. Hybridization conditions included the use of a microwave oven to denature target and probe nucleic acids and a five-step protocol for detection of biotinylated hybrids. In situ hybridization detected CAV nucleic acid in thymus tissue from experimentally infected birds after 6 hours, 3 days, and 7 days fixation time in formalin. However, immunocytochemical detection of CAV antigen was severely impaired if tissue was fixed in formalin for more than 6 hours. PMID- 8452494 TI - Control of established Salmonella typhimurium intestinal colonization with in vivo-passaged anaerobes. AB - Broiler chickens were inoculated orally with 10(6) Salmonella typhimurium on the day of hatch. Twenty-four to 72 hr after challenge, the chicks were inoculated orally with cecal microflora that had been repeatedly passed through lactose-fed broiler chicks. In vivo passage proved to be a convenient and practical method for preserving protective anaerobic flora. These organisms effectively reduced S. typhimurium concentrations in the cecal contents by 4-5 orders of magnitude, even when given 24 to 72 hr after Salmonella challenge inoculation. PMID- 8452495 TI - Resistance to Salmonella gallinarum, S. pullorum, and S. enteritidis in inbred lines of chickens. AB - Chickens of six inbred lines were inoculated intramuscularly with a range of doses of either Salmonella gallinarum, S. pullorum, or S. enteritidis, and levels of mortality were compared. For each serotype, large differences in mean lethal doses were observed for the different lines: Lines that had previously been shown to be resistant to S. typhimurium were also found to be resistant to S. gallinarum, S. pullorum, and S. enteritidis, and lines susceptible to S. typhimurium were also more susceptible to the other serotypes. These results suggest that there may be a general mechanism of resistance that may apply to all serotypes of Salmonella in chickens. PMID- 8452496 TI - Effect of infective dose on humoral immune responses and colonization in chickens experimentally infected with Salmonella typhimurium. AB - The influence of infective dose on chicken immunogenicity was examined in 1-week old chickens. Chickens were infected orally with various doses of chi 3761 or chi 3985. Fecal shedding, colonization of the cecum, and induction of Salmonella specific serum immunoglobulin isotypes were analyzed over a 5-week period. The delta cya delta crp Salmonella typhimurium vaccine strain chi 3985 was used to assess the effect of vaccination dose on protection after oral vaccination of chickens at 1 day and 2 weeks of age. Wild-type S. typhimurium strain chi 3761 was used to challenge vaccinated and unvaccinated chickens at 6 weeks of age, and the recovery of Salmonella from the cecum was used as a measure of protection. Infection of 1-week-old chickens with chi 3985 was more effective in reducing fecal excretion and cecal colonization than was infection with chi 3761. Double vaccination with 10(8) or 10(7) CFU of chi 3985 at 1 day and 2 weeks of age protected vaccinated chickens against cecal colonization by the challenge strain chi 3761. Immunogenicity of Salmonella is dose and genotype-dependent. PMID- 8452497 TI - Mycoplasma gallisepticum F-vaccine strain-specific polymerase chain reaction. AB - A Mycoplasma gallisepticum (MG) F-vaccine strain polymerase chain reaction (PCR) (MGF-PCR) was developed and standardized. The origin of the primers was a clone (p08-M6#17) that contained an MG F-strain-specific DNA fragment of 6.0 kilobase pairs designated fMGF-1. Both ends of fMGF-1 (BamHI and EcoRI) were sequenced, and regions adequate for the primers were chosen. Seven 25-base primers were synthesized, and two near the EcoRI end (MGF-P1 left [L] and right [R]) were selected for MGF-PCR, MGF-P1 L and R amplified a DNA product of 524 base pairs (bp) that was directed at F-strain-related MG only. None of 16 other species of avian mycoplasmas that were tested yielded MGF-PCR product. MGF-PCR was able to consistently detect F-strain samples containing 54 cells or more and inconsistently (at least one positive out of five replicates) in samples with fewer organisms. The MGF-PCR products were visualized either by gel electrophoresis or Southern blot hybridization with a probe containing an identical base sequence as the 524-bp product amplified by MGF-PCR. The MGF-PCR was 1000 to 10,000 times more sensitive than dot-blot assays using two MG F strain-specific probes. PMID- 8452498 TI - Amplification of Mycoplasma iowae using polymerase chain reaction. AB - Based on sequence data of Mycoplasma iowae recombinant DNA probe, pMI-12, two 25 base primers were synthesized for use in the polymerase chain reaction (PCR). An M. iowae species-specific 299-base pair product was amplified by the primers. An annealing temperature of 58.5 C was critical for detecting all members of this heterogeneous species while maintaining specificity of the M. iowae PCR. The minimum amount of target DNA detected by M. iowae PCR was 1 pg, which was 1000 times more sensitive than the dot-blot assay using M. iowae recombinant DNA probes. PMID- 8452499 TI - Efficacy of toltrazuril against experimental infections with Eimeria labbeana and E. columbarum in racing pigeons. AB - The efficacy of toltrazuril against heavy experimental Eimeria labbeana and E. columbarum infections in racing pigeons was investigated. Pigeons were treated with toltrazuril at a dose of 20 mg/kg body weight before, during, and after the pre-patent period. In pigeons treated during pre-patency (1-5 days postinoculation [PI]), a 99.9% reduction in oocyst output was observed at day 7 PI. Treatment during patency (6-7 days PI) resulted in an interruption of oocyst shedding within 3 to 4 days. Pigeons treated with toltrazuril up to 14 days before the experimental infection showed on average a reduction of more than 97% in the number of oocysts in individual fecal samples. Finally, at reinfection, the immune response of pigeons previously treated during pre-patency was not altered compared with the response of infected unmedicated controls. PMID- 8452500 TI - Comparative efficacy of the B-1 and VG/GA vaccine strains against velogenic viscerotropic Newcastle disease virus in chickens. AB - Groups of eight 1-day-old white rock chickens were vaccinated with either B-1 or VG/GA strain of Newcastle disease virus (NDV) by eyedrop instillation. Some of the chickens were vaccinated a second time at 17 days of age. Eight groups of chickens vaccinated either once or twice were challenged with the California 1083 strain of velogenic viscerotropic Newcastle disease virus (VVNDV) at 30 days of age by either intramuscular injection or eyedrop instillation. One group of unvaccinated control chickens was challenged by eyedrop instillation. All eight unvaccinated controls, two of the 16 B-1 vaccinates, and none of the 16 VG/GA vaccinates died following challenge. There were no obvious differences in pre challenge serum antibody levels among the vaccinates. Only the twice-vaccinated chickens that were challenged by eyedrop and the unchallenged vaccinates failed to show a marked rise in serum antibody titers. The VG/GA strain of NDV provided protection against the mortality associated with VVNDV challenge similar to that provided by the B-1 strain within the conditions of this experiment. PMID- 8452501 TI - Occlusive laryngotracheitis in turkeys following drinking water administration of gentian violet. AB - Acute respiratory signs and increased mortality due to suffocation occurred in a flock of 5-week-old male turkey poults following water administration of gentian violet. Gross lesions of laryngeal edema and occlusion of the tracheal opening with caseous plugs were present. Microscopic lesions in the tracheas consisted of vascular congestion, mucosal degeneration, and necrosis. The condition was reproduced experimentally in turkey poults by giving drinking water containing gentian violet. PMID- 8452502 TI - Enterococcus durans infection in young chickens associated with bacteremia and encephalomalacia. AB - Two unrelated flocks of chicks experienced elevated mortality from 4 to 10 days of age. Clinical signs in affected birds included a full range of neurological disorders. Livers and spleens were grossly enlarged at necropsy. Enterococcus durans was isolated from multiple organs, including brains. Histologically, there were multifocal coagulative necrosis in the liver, areas of malacia in brain stem, and cerebellar white matter. Inoculation of 1-day-old chicks with a suspension of E. durans resulted in bacteremia but did not produce the lesions observed in field cases. PMID- 8452503 TI - Wry necks associated with Mycoplasma meleagridis infection in a backyard flock of turkeys. AB - Two 5-week-old bronze turkeys were submitted with crooked necks that could not be straightened. Both birds were serologically and culturally positive for Mycoplasma meleagridis (MM). Histologically, there were lymphoid follicles in the cranial thoracic and cervicoclavicular air sacs, and inflammatory changes in the cartilage of some cervical vertebrae. This appeared to be a case of MM-associated wry necks. PMID- 8452504 TI - Occurrence of velogenic viscerotropic Newcastle disease in pet and exotic birds in 1991. AB - In 1991, velogenic viscerotropic Newcastle disease (VVND) was diagnosed in domestic psittacine birds in six states: Illinois, Indiana, Michigan, Texas, California, and Nevada. In the first four states, the disease assumed outbreak proportions. The affected psittacine birds--yellow-headed Amazon parrots (Amazona ochrocephala oratrix), yellow-naped Amazon parrots (Amazona ochrocephala auropalliata), cockatiels (Nymphicus hollandicus), and conures (unknown species)- exhibited respiratory and/or central nervous system signs. The velogenic viscerotropic Newcastle disease virus (VVNDV) was isolated from cloacal and tracheal swabs and various tissues, such as the lung, trachea, distal intestine, and spleen. The origin of the birds could not be established. The disease in the six states was promptly controlled, with no evidence that domestic poultry had been exposed. Also, VVNDV was isolated from quarantined birds intended for importation into the United States. Included were 53 moustached parakeets (Psittacula alexandri fasciata), a mynah (Gracula religiosa), a drongo (Dicrurus sp.), and three partridges (family Phasianidae). Groups of birds that yielded VVNDV were denied entry into the United States. Birds that are illegally imported and therefore not tested for the presence of foreign animal pathogens are a potential source of VVNDV and a threat to domestic poultry and caged birds. PMID- 8452505 TI - Description of osteomyelitis lesions associated with Actinomyces pyogenes infection in the proximal tibia of adult male turkeys. AB - Actinomyces pyogenes was isolated from osteomyelitis lesions from the proximal tibia of mature tom turkeys. Gram-stained impression smears of the lesions resulted in bacteria that appeared as club-shaped, gram-positive pleomorphic rods. The bacteria grew better in a reduced-oxygen environment. The lesions were well demarcated and cavernous, ranging from purulent to caseous in consistency. PMID- 8452506 TI - Resistance of chicks against reinfection with Leucocytozoon caulleryi. AB - Chickens were inoculated with five to 40 sporozoites of Leucocytozoon caulleryi at 1 to 9 days of age. Mortality, parasitemia, appearance of serum-soluble antigen, and antibodies were examined. Chickens that survived primary infection were reinoculated with 3 x 10(3) to 1 x 10(4) sporozoites and examined for resistance against reinfection by the same criteria used in primary infection. After primary infection, up to 80% of chickens died of leucocytozoonosis. Surviving chickens showed parasitemia from 13 days to 23 or 24 days after inoculation. Serum-soluble antigen and antibodies were detected in most chickens, except for some chickens that were infected at 1 to 3 days of age. After secondary infection, only a few chickens that received primary infection at 1 to 7 days of age showed a small number of parasites in their peripheral blood. Most of the other chickens were resistant to reinfection. Resistance to reinfection was recognized in some chickens that had not showed antibody production before secondary infection. PMID- 8452507 TI - Pharmacokinetics of doxycycline after parenteral administration in the Houbara bustard (Chlamydotis undulata). AB - Fourteen adult Houbara bustards (Chlamydotis undulata) infected with Chlamydia psittaci were administered doxycycline at 100 mg/kg body weight in seven intramuscular or subcutaneous injections at intervals of 7, 7, 7, 6, 6, and 5 days. Blood levels of doxycycline were measured after the first and seventh injections at the following intervals: 0, 12, 24, 36, 48, 72, 96, 120, 144, 168, and 180 hours. During these two periods, most of the birds showed plasma doxycycline levels in excess of 1 micrograms/ml, demonstrating effective doxycycline levels for 45 days. A multifactorial analysis of variance revealed no significant differences between males and females, between the two routes of administration, or among all four factors. PMID- 8452508 TI - Leg strength and performance of large white tom turkeys fed various protein and energy levels. AB - Three floor-pen experiments were conducted to determine the effects of varying protein and energy levels on body weight, feed efficiency, mortality, bone breaking-strength, and bone ash, calcium, and phosphorus in large white male turkeys. Increasing metabolizable energy by 100 kcal/kg diet increased body weight and feed efficiency. Increasing dietary protein during starter or finisher periods by 15% resulted in increased body weights by as much as 12%. Modifying dietary protein and energy levels over these ranges did not affect bone strength of toms at market weight. PMID- 8452509 TI - Protective effect of used poultry litter and lactose in the feed ration on Salmonella enteritidis colonization of leghorn chicks and hens. AB - The effect of dietary administration of lactose and used poultry litter, containing cecal and fecal droppings from adult broilers, was evaluated for protective effects against Salmonella enteritidis colonization in leghorn chicks and 16-week-old hens. The addition of used litter as 5% of the feed ration significantly decreased (P < 0.01) Salmonella cecal and organ colonization in the chicks. Provision of used litter or used litter and lactose in the feed failed to provide protection against Salmonella colonization in the hens. The results indicated that resistance to S. enteritidis colonization may be effectively increased in leghorn chicks by exposure to adult intestinal flora present in used litter. Furthermore, the results suggest that microbiological strategies employing adult intestinal microflora that increase Salmonella colonization resistance in young chicks may be ineffective in older hens. PMID- 8452510 TI - Classification, pathogenicity, and drug susceptibility of hemolytic gram-negative bacteria isolated from sick or dead chickens. AB - Fifteen hemolytic gram-negative bacteria were isolated from the respiratory tracts of sick birds suffering from a long-lasting respiratory syndrome or from the bone marrow of dead birds distributed in the southern part of Taiwan. These were classified as Pseudomonas aeruginosa (10 isolates), Pseudomonas fluorescens (2 isolates), Pseudomonas stutzeri (1 isolate), Pasteurella haemolytica (1 isolate), and Proteus morganii (1 isolate). Each isolate was inoculated intraperitoneally into one group of ten 4-week-old male white leghorn chickens. Mortality and lesions were scored daily for 1 week. Three of the 10 isolates of Pseudomonas aeruginosa caused 100% mortality. Six other isolates of Pseudomonas aeruginosa and the one isolate of Proteus morganii caused 50% mortality. The remaining isolates induced less than 30% mortality. The sole nonpathogenic sample was one isolate of Pseudomonas fluorescens. When therapeutic levels of 22 antibiotics or sulfa drugs were evaluated for their inhibitory activity against the 15 isolates, the most effective were apramycin (15/15), gentamicin (15/15), spectinomycin (13/15), oxytetracycline (8/15), and sulfachloropyrazine (7/15). The least effective were ampicillin, cloxacillin, and tiamulin, which were not effective against any of the isolates. The 14 other drugs were of very low (> 4/15) effectiveness. Most of the isolates studied were virulent for chickens and very resistant to currently used drugs. PMID- 8452511 TI - Transfer of IgG from serum to lachrymal fluid in chickens. AB - Pure 125I-radiolabeled chicken IgG was inoculated intravenously into 2-week old chickens. Radioactivity in lachrymal fluid samples was first detected 10 minutes postinoculation (PI). Radioactivity levels declined up to day 20 PI, when they reached marginal levels. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by autoradiography of lachrymal fluid samples, taken daily for 16 days, showed the presence of radioactive polypeptides in the same positions as their stained control counterparts at molecular weights corresponding to heavy and light chains of immunoglobulins. Radiolabeled IgG also was detected in serum samples of the inoculated chickens. SDS-PAGE followed by autoradiography of lachrymal samples taken until day 16 PI showed similar results. These results demonstrate that transfer of IgG from serum to lachrymal fluid does occur in chickens. PMID- 8452512 TI - Protective immunity against coccidiosis elicited by radiation-attenuated Eimeria maxima sporozoites that are incapable of asexual development. AB - Eimeria maxima oocysts were exposed to various doses of gamma radiation that did not affect sporozoite invasion of intestinal epithelium but did prevent subsequent merogonic development therein. Although merogony and oocyst formation were inhibited, parasites exposed to 12 kRad radiation induced a level of immunity against E. maxima challenge equivalent to that induced by non-irradiated oocysts. Chickens immunized per os with 20 kRad-treated E. maxima oocysts were not protected against coccidial challenge. Immunization of chickens with a single low dose (five oocysts) of non-irradiated (0 kRad) or irradiated (12 kRad) E. maxima was effective in preventing weight depression after coccidial challenge. Immunofluorescence staining of intestinal tissue from chickens infected with irradiated (12 or 20 kRad) or non-irradiated (0 kRad) E. maxima oocysts with developmental stage-specific monoclonal antibodies showed that sporozoite invasion was similar in all groups. However, merogonic development was not observed at any time postinfection in chickens infected with irradiated oocysts, unlike the case with chickens infected with non-irradiated parasites. These results suggest that sporozoite-infected host cells are capable of eliciting complete protection against E. maxima challenge. PMID- 8452513 TI - Effect of exercise on the cardiovascular and respiratory systems of heavy turkeys and relevance to sudden death syndrome. AB - The cardiorespiratory response to walking exercise was studied in 14-to-18-week old male and female heavy turkeys. Blood pressure, electrocardiograms, respiratory rate, body temperature, blood gases, and electrolytes were measured at rest and after exercise at two different room temperatures. After exercise, systolic, diastolic, and mean blood pressures decreased, and heart rate and body temperature increased, while a severe lactic acidosis developed, in both sexes and at both room temperatures. Fifty-four percent of the turkeys developed arrhythmias, mostly a transient post-exercise sinus arrhythmia of no clinical significance. Changes in electrolytes were clinically insignificant. Blood gases remained within normal limits, demonstrating adequate gas-exchange and pulmonary capability. Within the limits of this study, the cardiac capacity of the heavy turkey in response to exercise appeared very limited. The pathogenesis of sudden death syndrome of turkeys is still unknown, but cardiovascular changes occurring after exercise could be severe enough to cause death. PMID- 8452514 TI - Effect of exercise on cardiac output and other cardiovascular parameters of heavy turkeys and relevance to the sudden death syndrome. AB - The cardiovascular response to treadmill exercise was studied in 14-to-18-week old male and female heavy turkeys. Arterial blood pressure, cardiac output, body temperature, and heart rate were measured before and during each period of exercise. Total peripheral resistance, stroke volume, and stroke index were calculated from those parameters. Systolic, diastolic, and mean blood pressures significantly decreased during exercise. Cardiac output increased during exercise in males and females by 64% and 23%, respectively, while total peripheral resistance fell by approximately 40% in both sexes. Exercise had no significant effect on stroke volume and stroke index. The cardiac functional capacity of the heavy turkey in response to mild exercise appears very limited. This failure of the cardiovascular system to adequately respond to increased metabolic needs suggests that hemodynamic failure is a major component in the pathogenesis of sudden death syndrome of turkeys. PMID- 8452516 TI - Benzyloxycarbonyl-D-Phe-Pro-methoxypropylboroglycine: a novel inhibitor of thrombin with high selectivity containing a neutral side chain at the P1 position. AB - Thrombin, the blood-clotting enzyme, is a serine proteinase with trypsin-like specificity and is able to cleave Arg-Xaa peptide bonds but only in a very limited number of substrates (and sites therein). For the prevention and treatment of thrombosis the control of thrombin activity is a key target, and a variety of synthetic inhibitors have been introduced recently, all of which have a positive charge at the P1 site. We report the synthesis of the first example of a new class of inhibitor containing a neutral side chain at the P1 site, the peptide benzyloxycarbonyl-D-Phe-Pro- methoxypropylboroglycine. The peptide is a potent inhibitor of thrombin [Ki (limiting) = 7 nM] and is highly selective for its target enzyme in respect of other serine proteinases. This may be expected to confer considerable advantage in terms of specificity of action and reduced toxicity over conventional, positively charged, inhibitors. PMID- 8452515 TI - The inducible transcription factor NF-kappa B: structure-function relationship of its protein subunits. PMID- 8452517 TI - Characterization of structural and folding properties of streptokinase by n.m.r. spectroscopy. AB - The structure and physical properties of the fibrinolytic protein streptokinase have been investigated by 1H-n.m.r. spectroscopy. Well-resolved one- and two dimensional spectra have been obtained for this molecule of molecular mass 47 kDa. Titration of all nine histidine residues has shown that these display a range of pKa values, between 5.6 and 8.2, revealing a variety of environments for these residues in the protein structure. Although at least eight histidine residues can be reversibly modified by diethylpyrocarbonate, only one is sufficiently exposed to be reactive towards photo-excited dye in chemically induced dynamical nuclear polarization spectroscopy experiments. Unfolding studies have been performed by thermal and chemical means. Evidence is presented here for several distinct unfolding transitions suggesting that the protein consists of at least three domains which have independent stability, and that the protein can exist in a number of partially folded states. For one of these, that formed in 2 M guanidine hydrochloride, it has been shown that the N-terminal region of the molecule is extensively unfolded, while other regions of the protein remain in native-like folded states. PMID- 8452518 TI - Isolation and characterization of AMP deaminase from mammalian (rabbit) myocardium. AB - AMP deaminase (AMP aminohydrolase, EC 3.5.4.6) is a ubiquitous enzyme in eukaryotes, which may play a role in ATP catabolism during myocardial ischaemia. We report isolation of AMP deaminase from rabbit myocardium with a 19% recovery and a 650-fold enrichment, using a newly devised protocol involving sequential cation-exchange, gel-permeation and affinity chromatographies. The cardiac AMP deaminase preparation described was electrophoretically and chromatographically homogeneous and contained one unique N-terminal residue (leucine). The isolated enzyme was sensitive to various cations (K+, Mg2+, Ca2+). The pH optimum of purified cardiac AMP deaminase was 6.8, its pI was 6.5, and it displayed substrate-specificity toward 5'-AMP. The subunit molecular mass of rabbit heart AMP deaminase on SDS/PAGE (81 kDa) and the holoenzyme molecular mass as estimated by non-denaturing size-exclusion h.p.l.c. (330 kDa) indicated that the native enzyme was a tetramer. Cardiac AMP deaminase displayed a sigmoidal substrate saturation curve in the presence of 100 mM KCl. Apparent Michaelis constants were a Km of 5.8 mM AMP and a Vmax. of 11.1 mumol/min per mg of protein. ATP and ADP were positive allosteric effectors of cardiac AMP deaminase: the apparent Km was decreased to 1.7 mM by 1.0 mM ATP. The enzyme was inhibited by GTP, coformycin, coformycin 5'-phosphate, palmitoyl-CoA, inorganic phosphate compounds, and the metal chelator o-phenanthroline. No inhibition either by product nucleotide (IMP) or by nicotinamide nucleotides was detected when these agents were examined at concentrations up to 2.5 mM. We conclude that this enzyme preparation offers a means by which the kinetic mechanism and regulation of mammalian cardiac AMP deaminase may be directly investigated. PMID- 8452519 TI - Cytokine induction of haem oxygenase mRNA in mouse liver. Interleukin 1 transcriptionally activates the haem oxygenase gene. AB - Accumulation of the mRNA coding for haem oxygenase (HO, EC 1.14.99.3) was stimulated by treating mice with endotoxin (lipopolysaccharide, LPS; 20 micrograms/mouse intraperitoneally), suggesting that haem catabolism is a target of infection and inflammation in vivo. Therefore various cytokines, possible mediators for the biological responses to LPS, were administered intraperitoneally to mice, and the levels of HO mRNA were measured by Northern blotting analysis using the rat HO cDNA as a probe [Shibahara, Muller, Taguchi and Yoshida (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 7865-7869]. Marked induction of HO mRNA was observed 2 h after administration of interleukin 1 (IL-1) (34 fold) and tumour necrosis factor (19.5-fold) (5 micrograms/mouse), whereas interleukin 6 (6.2 micrograms/mouse) was much less active (3.5-fold) and interleukin 2 (25 micrograms/mouse) and interferon-gamma (3 micrograms/mouse) were ineffective. HO mRNA induced by the cytokines of LPS accumulated rapidly (maximum at 1-2 h after administration), preceding the elevation of HO enzymic activity. Treatment of mice with IL-1 stimulated the transcription of the HO gene by 4-fold, as assessed by in vitro nuclear-run-on assay. These results indicate that enzymic haem catabolism in the liver is a process inducible in vivo by inflammatory cytokines, which up-regulate HO synthesis at the transcriptional level. Increased removal of haem might be part of the protective mechanisms elicited by the acute-phase response, possibly to reduce the pro-oxidant state of the cell. PMID- 8452520 TI - 1,2-alpha-D-mannosidase from Penicillium citrinum: molecular and enzymic properties of two isoenzymes. AB - Two isoforms of acidic 1,2-alpha-D-mannosidases have been isolated from culture filtrate of Penicillium citrinum. The pI values of the two forms, designated 1,2 alpha-mannosidase Ia and Ib, were 4.6 and 4.7 respectively. Isoenzymes Ia and Ib exhibited the same molecular mass which was determined to be 53 kDa by SDS/PAGE and 54 kDa by gel-permeation chromatography. Enzymes Ia and Ib hydrolysed yeast mannan and 1,2-alpha-linked mannooligosaccharides, but did not hydrolyse p nitrophenyl alpha-D-mannoside. The optimal pH for the hydrolysis of Man(alpha 1- >2)Man was 5.0 for both isoenzymes. Similar kinetic parameters were determined for the two forms. Activation energy was a little lower for Ia than Ib. There was little difference between the enzymes with regard to their performance at acidic or alkaline pH. The N-terminal amino acid sequences of the two enzymes were identical. Analysis of C-terminal peptides, which were prepared by tryptic digestion and anhydrotrypsin-agarose chromatography, showed that Ia and Ib had the same amino acid sequences in the C-terminal region. Tryptic digestion revealed a slight difference between the isoenzymes in the pattern of cleaved peptides on SDS/PAGE. PMID- 8452521 TI - Further observations on the Mg-protoporphyrin IX monomethyl ester (oxidative) cyclase system. AB - The Mg-protoporphyrin IX monomethyl ester (oxidative) cyclase was strongly inhibited by CN- and N3- in a reconstituted system, but was inhibited slightly or not at all by the same reagents in intact developing chloroplasts. Known inhibitors of cytochrome P-450 processes showed no consistent effect. Benzoquinone and quinol, which can give rise to the same semiquinone by one electron redox events, were strong inhibitors of the cyclase. It was previously shown that O2 and a source of electrons are required in the cyclization process. The substrates for the dehydrogenases of the pentose phosphate pathway (glucose 6 phosphate and 6-phosphogluconate) were effective reductants in the reconstituted system with supernatant that had been dialysed or passed through Sephadex G-50, in the absence of added NADP+. However, inhibitor studies suggested that the electrons from these sugar phosphates reached the cyclase system via NADPH. Therefore we infer the presence of protein-bound NADP+ that can be reduced by glucose 6-phosphate and 6-phosphogluconate and donate reducing equivalents to the cyclase system. This bound NADPH pool may be particularly effective in the cyclization process, owing to channeling. These findings are discussed in relation to the results of a companion paper [Whyte and Castelfranco (1993) Biochem. J. 290, 361-367] on the breakdown of chloroplast pigments in the same reconstituted system. PMID- 8452522 TI - Breakdown of thylakoid pigments by soluble proteins of developing chloroplasts. AB - In the presence of Triton X-100 (TX-100) or imazalil, plastidic pigments were degraded by a soluble enzyme extracted from developing chloroplasts. This bleaching was not photochemical and required oxygen; it was not inhibited by superoxide dismutase or catalase, but was strongly inhibited by benzoquinone, quinol, phenazine methosulphate and, more weakly, by other reagents. Synthetic intermediates of chlorophyll biosynthesis, e.g. Mg(II)-protoporphyrin IX monomethyl ester, was also degraded. This reaction was compared with the bleaching catalysed by soybean (Glycine max) lipoxygenase. The plastidic system required TX-100 and was inhibited by unsaturated fatty acids, whereas lipoxygenase required a polyunsaturated fatty acid and was inhibited by TX-100. The bleaching capability of the stromal extract decreased with age if the seedlings were placed in the greenhouse to allow further development of the chloroplasts. A direct relationship was observed between the promotion of pigment bleaching by TX-100 and the inhibition of the in vitro synthesis of divinylprotochlorophyllide. This bleaching reaction is discussed on the basis of interference by TX-100 with the normal O2-requiring anabolic processes of developing chloroplasts. PMID- 8452523 TI - Effect of heterologous expression of acyl-CoA-binding protein on acyl-CoA level and composition in yeast. AB - We have expressed a bovine synthetic acyl-CoA-binding protein (ACBP) gene in yeast (Saccharomyces cerevisiae) under the control of the GAL1 promoter. The heterologously expressed bovine ACBP constituted up to 6.4% of total cellular protein and the processing was identical with that of native bovine ACBP, i.e. the initiating methionine was removed and the following serine residue was N acetylated. The expression of this protein did not affect the growth rate of the cells. Determination of the yeast acyl-CoA pool size showed a close positive correlation between the ACBP content of the cells and the size of the acyl-CoA pool. Thus ACBP can act as an intracellular acyl-CoA pool former. Possible physiological functions of ACBP in cells are discussed. PMID- 8452524 TI - Subcellular distribution of agonist-stimulated phosphatidylinositol synthesis in 1321 N1 astrocytoma cells. AB - In an inositol-depleted 1321 N1 astrocytoma cell line, propranolol at 0.5 mM concentration and carbachol in the presence of Li+ induce a large increase (30-60 fold) in the amount of CMP-phosphatidate, the lipid substrate of PtdIns synthase. The actions of both agents on CMP-phosphatidate accumulation were reversed by co incubation with 1 mM inositol. In cells grown in the presence of 40 microM inositol the propranolol- and carbachol-mediated CMP-phosphatidate accumulation was much smaller (2-4-fold). Propranolol- and carbachol-mediated increases in CMP phosphatidate accumulation were at least additive in both inositol-replete and depleted cells. The subcellular distribution of accumulated CMP-phosphatidate was investigated by sucrose-density-gradient centrifugation of a lysate of inositol depleted cells. There were two coincident peaks of carbachol-stimulated [3H]CMP phosphatidate and PtdIns synthase activity, respectively. The first peak of accumulated [3H]CMP-phosphatidate and PtdIns synthase activity is characteristic of a 'light vesicle' fraction, since it sediments at sucrose densities similar to that of endocytosed 125I-transferrin. The later peak, containing both carbachol stimulated [3H]CMP-phosphatidate and PtdIns synthase activity, has a distribution in the gradient that is similar to NADPH-cytochrome c reductase activity, an endoplasmic-reticulum marker. By contrast, propranolol-stimulated [3H]CMP phosphatidate accumulates in membranes which sediment as a single peak corresponding to the endoplasmic-reticulum marker. These observations suggest that agonist-stimulated PtdIns synthesis occurs in the endoplasmic reticulum and in at least one additional membrane compartment which is insensitive to propranolol, an inhibitor of endoplasmic-reticulum phosphatidate phosphohydrolase. PMID- 8452525 TI - Kinetic characterization of guanine-nucleotide-induced exocytosis from permeabilized rat mast cells. AB - We have measured the time course of secretion of hexosaminidase from rat mast cells permeabilized (in simple buffered NaCl solutions) in response to guanine nucleotides [GTP or guanosine 5'-[gamma-thio]triphosphate (GTP[S])] and Ca2+. In these experiments, ATP was excluded from the system (and the cells were pretreated with metabolic inhibitors). For cells permeabilized in the absence of Mg2+ but in the presence of Ca2+, secretion commences promptly in response to addition of GTP; when Mg2+ (2 mM) is provided, secretion commences after an extended delay, much higher concentrations of GTP are required, and the final extent of secretion is decreased. Ongoing secretion due to GTP and Ca2+ is abruptly terminated by addition of Mg2+ to cells initially stimulated in its absence. In contrast, although Mg2+ has no effect on the sensitivity to the non hydrolysable analogue GTP[S], its absence does nevertheless cause delays in the onset of secretion triggered by the addition of GTP[S] to cells initially permeabilized in the presence of Ca2+ (micromolar range, again in the absence of ATP). However, exocytosis from cells triggered with Ca2+ after permeabilization in the presence of high concentrations of GTP[S] is instantaneous. The delays due to triggering by GTP[S] have GTP[S]-concentration-dependent and -independent components. The guanine-nucleotide-concentration-dependent component is expressed as an extended duration of delay as the concentration of GTP[S] is decreased, and may reflect the binding of GTP[S] to GE. The concentration-independent component is manifested as a limiting delay which cannot be further diminished by increasing the guanine nucleotide concentration. The duration of the limiting delay is sensitive to the identity of the stimulating nucleotide (GTP < GTP[S] < p[NH]ppG) and may reflect the time taken for an activating conformational change to occur after binding. Since both components of the delays are abolished by the presence of Mg2+, both the binding of guanine nucleotide and the activation of GE appear to be Mg(2+)-dependent. We therefore conclude that nucleotide binding, activation and the GTPase activity of GE are strongly dependent on Mg2+, in common with the same three processes in Gs and Gi. PMID- 8452526 TI - Developmental pattern of branched-chain 2-oxo acid dehydrogenase complex in rat liver and heart. AB - The developmental pattern of the branched-chain 2-oxo acid dehydrogenase complex was examined in the liver and heart of the rat throughout the suckling period. Basal activity and total activity of the complex were measured as a function of age. The hepatic enzyme activity increased dramatically and was 100% active (dephosphorylated) during the suckling period. The level of protein kinase associated with the complex was particularly low at birth, but like the complex increased throughout the suckling period. The level of heart enzyme also increased as a function of age, but only about 30-45% of the enzyme was active throughout the suckling period. Very low protein levels of liver and heart branched-chain 2-oxo acid dehydrogenase were detected by immunoblot analysis in newborn rats. The mRNA levels for the liver E1 alpha, E1 beta, and E2 subunits in newborn rat were 30%, 19%, and 4% of adult levels respectively. The capacity of the neonatal rat for oxidizing leucine in vivo was low at birth and increased with age. 4-Methyl-2-oxopentanoate was more toxic when given to newborn and 3-day old pups than 21-day-old pups, as expected from the relative capacities of their tissues to dispose of branched-chain 2-oxo acids by oxidation. Force-feeding suckling rats a protein-free artificial milk formula resulted in partial inactivation of the hepatic branched-chain 2-oxo acid dehydrogenase complex, indicating that the liver of the suckling rat can adapt to conserve branched chain amino acid residues during periods of protein deficiency. PMID- 8452527 TI - Effect of saposins on acid sphingomyelinase. AB - The effect of saposins (A, B, C and D) on acid sphingomyelinase activity was determined using a crude human kidney sphingomyelinase preparation and a purified sphingomyelinase preparation from human placenta. Saposin D stimulated the activity of the crude enzyme by increasing its apparent Km and Vmax. values for sphingomyelin hydrolysis. Unlike the crude enzyme, the activity of the purified enzyme was strongly inhibited by saposin D as well as other saposins. Saposin D decreased the apparent Km and Vmax values of purified sphingomyelinase activity. The effects of saposin D on the activity of different sphingomyelinase preparations appear to depend on Triton X-100, which is present in the crude enzyme but not in the purified enzyme. When the detergent was removed from the crude preparation, the effect of saposin D changed from being stimulatory to inhibitory. Conversely, when the detergent is added to the purified enzyme, the effect of saposin D on sphingomyelinase activity changed from being inhibitory to stimulatory. While other saposins were inhibitory or had no effect on sphingomyelinase activity in the above assay system, not only saposin D but also saposins A and C exhibited a stimulatory effect upon purified sphingomyelinase activity when the substrate, sphingomyelin, was added in the form of liposomes without detergent. Saposin B was not only inhibitory in the liposome system, but also reduced the stimulatory effect of saposins A, C and D. These observations indicate that the stimulatory effect of saposins A, C and D on acid sphingomyelinase activity is greatly influenced by the physical environment of the enzyme and suggest that similar effects by saposins may be exerted in lysosomal membranes. PMID- 8452528 TI - Purification and partial sequencing of myristoyl-CoA:protein N myristoyltransferase from bovine brain. AB - The enzyme myristoyl-CoA:protein N-myristoyltransferase (NMT; EC 2.3.1.97) catalyses the transfer of myristic acid to the N-terminal glycine residue of cell and viral proteins. In this report the purification and partial sequencing of this enzyme from bovine brain is described. Using a combination of ammonium sulphate precipitation, chromatography on DEAE-Sepharose and affinity chromatography on CoA-agarose the enzyme was purified some 40-fold. Size exclusion chromatography of this material in the presence of myristoyl-CoA yielded two peaks of enzyme activity with apparent molecular masses of 66 kDa and 43 kDa. Chromatography of the CoA-affinity-purified material on MONO-S followed by size-exclusion chromatography in the presence of myristoyl-CoA resulted in the isolation of the large form of the enzyme purified 3000-fold. Analysis by SDS/PAGE of this material showed a major 60 kDa silver-stained band. Similar analysis of the 43 kDa enzyme fraction from the same separation showed that this fraction contained several proteins including a major component with an apparent molecular mass of 49 kDa. Attempts at N-terminal sequencing of the 66 kDa form of the enzyme were unsuccessful and therefore this material was digested with trypsin and the resulting peptides separated by reverse-phase h.p.l.c. N-terminal protein sequencing of these peptides yielded sequences which show sequence similarity to those of yeast N-myristoyl-transferase. PMID- 8452529 TI - The interaction of 6-propionyl-2-(NN-dimethyl)aminonaphthalene (PRODAN)-labelled actin with actin-binding proteins and drugs. AB - The influence of various actin-binding proteins and drugs on the fluorescence emission of rabbit muscle actin labelled with the fluorescent probe acrylodan (6 acryloyl-2-dimethylaminonaphthalene) at Cys-374, the penultimate amino acid residue of the actin amino acid sequence, was studied. Addition of myosin, tropomyosin or phalloidin, agents known to bind only to filamentous F-actin, did not change the emission energy or the integrated intensity of the fluorescence spectrum. The presence of heavy meromyosin or of the glycolytic enzyme aldolase led to a small (approx. 2%) increase in the integrated intensity, and in the energy of the emitted fluorescence. The interaction of 6-propionyl-2-(NN dimethyl)aminonaphthalene (PRODAN)-F-actin with pancreatic DNAase I and with a filament-severing 19 kDa protein from pig brain resulted in the gradual reduction of the integrated intensity of the emission and a red shift of the emission energy, suggestive of a disintegration of the actin filament structure. Profilin caused a < 10% change in the emission energy. Cytochalasin D reduced the integrated intensity of PRODAN-F-actin and red-shifted the emission energy, while cytochalasin B was without influence. Pancreatic DNAase I did not change the fluorescence emission of PRODAN-G-actin, suggesting that binding of this enzyme does not alter the environment of the probe. When the 19 kDa protein bound to PRODAN-G-actin, however, the integrated intensity was reduced and the emission energy was lowered. This effect was exploited to estimate the binding constant for the interaction between the 19 kDa protein and PRODAN-G-actin. The Kd was found to be about 0.25 microM. PMID- 8452530 TI - Purified hybrid insulin/insulin-like growth factor-I receptors bind insulin-like growth factor-I, but not insulin, with high affinity. AB - Hybrid insulin/insulin-like growth factor-I (IGF-I) receptors have previously been described in human placenta, but it has not been possible to study their properties in the presence of classical insulin receptors and type I IGF receptors. To facilitate the purification of hybrids, we produced an anti-peptide monoclonal antibody IGFR 1-2, directed against the C-terminal peptide of the type I IGF receptor beta-subunit. The antibody bound native human and rat type I IGF receptors, and reacted specifically with the beta-subunit on immunoblots. Solubilized placental microsomal membranes were depleted of classical type I IGF receptors by incubation with an immobilized monoclonal antibody IGFR 24-55, which reacts well with type I receptors but very poorly with hybrid receptors. Residual hybrid receptors were then isolated by incubation with immobilized antibody IGFR 1-2, and recovered by elution with excess of synthetic peptide antigen. Binding properties of hybrids were compared with those of immuno-affinity-purified insulin receptors and type I IGF receptors, by using the radioligands 125I-IGF-I and 125I-insulin. Hybrids bound approx. 20 times as much 125I-IGF-I as 125I insulin at tracer concentrations (approx. 0.1 nM). The binding of 125I-insulin, but not 125I-IGF-I, to hybrids increased after treatment with dithiothreitol to reduce disulphide bonds between the alpha-subunits. Hybrids behaved very similarly to type I receptors with respect to the inhibition of 125I-IGF-I binding by unlabelled IGF-I and insulin. By contrast, the affinity of hybrids for insulin was approx. 10-fold lower than that of classical insulin receptors, as assessed by inhibition of 125I-insulin binding by unlabelled hormone. It is concluded that the properties of insulin receptors, but not IGF receptors, are markedly affected by assembly as hybrid compared with classical structures, and that hybrids are more likely to be responsive to IGF-I than insulin under physiological conditions. PMID- 8452531 TI - Purification and characterization of rat epididymal-fluid alpha-D-mannosidase: similarities to sperm plasma-membrane alpha-D-mannosidase. AB - We have previously reported the occurrence and partial characterization of a novel alpha-D-mannosidase activity on rat sperm plasma membranes [Tulsiani, Skudlarek and Orgebin-Crist (1989) J. Cell Biol. 109, 1257-1267]. Here, we report the presence of a similar alpha-D-mannosidase activity in a soluble form in rat epididymal fluid. The soluble enzyme was purified nearly 500-fold with 9-12% recovery to a state approaching homogeneity using: (1) (NH4)2SO4 precipitation; (2) affinity chromatography on immobilized mannan and D-mannosamine; (3) ion exchange (DE-52) column chromatography; (4) molecular-sieve chromatography. The enzyme was eluted from the final column (Sephacryl S-400) at an apparent molecular mass of 460 kDa. When resolved by SDS/PAGE (under denaturing conditions), the enzyme showed a major protein band (115 kDa) and few very minor bands. The polyclonal antibody raised against the major protein band was found to cross-react with the alpha-D-mannosidase activity present in epididymal fluid (soluble) and detergent-solubilized spermatozoa from the rat and mouse. This result suggested that the soluble and membrane-bound enzyme activities shared a common antigenic site(s). The antibody was used to characterize further the alpha D-mannosidase activity(ies) present in the rat epididymal fluid and rat sperm plasma membranes. Data from these studies show that the two forms are similar in (a) subunit molecular mass, (b) substrate specificity and (c) inhibitory effect of several sugars. These similarities suggest that the soluble and membrane-bound alpha-D-mannosidase activities are isoforms. Immunoprecipitation studies after solubilization of the testis and epididymal particulate fraction from sexually immature rats show that the testis (but not the epididymis) contains the immunoreactive alpha-D-mannosidase activity. This result and the fact that spermatozoa from the rat rete testis show alpha-D-mannosidase activity indicate that the sperm enzyme is synthesized in the testis during spermatogenesis. PMID- 8452532 TI - Phosphorylation by casein kinase II affects the interaction of caldesmon with smooth muscle myosin and tropomyosin. AB - Smooth muscle caldesmon was phosphorylated by casein kinase II, and the effects of phosphorylation on the interaction of caldesmon and its chymotryptic peptides with myosin and tropomyosin were investigated. The N-terminal chymotryptic peptide of caldesmon of molecular mass 27 kDa interacted with myosin. Phosphorylation of Ser-73 catalysed by casein kinase II resulted in a 2-fold decrease in the affinity of the native caldesmon (or its 27 kDa N-terminal peptide) for smooth muscle myosin. At low ionic strength, caldesmon and its N terminal peptides of molecular masses 25 and 27 kDa were retarded on a column of immobilized tropomyosin. Phosphorylation of Ser-73 led to a 2-4-fold decrease in the affinity of caldesmon (or its N-terminal peptides) for tropomyosin. Thus phosphorylation of Ser-73 catalysed by casein kinase II affects the interaction of caldesmon with both smooth muscle myosin and tropomyosin. PMID- 8452533 TI - Modulatory effect of protein kinase C on thapsigargin-induced calcium entry in thyroid FRTL-5 cells. AB - The aim of the present study was to investigate the regulation of calcium influx in thyroid FRTL-5 cells. Stimulating Fura 2-loaded cells with thapsigargin rapidly increased the cytosolic Ca2+ concentration ([Ca2+]i), which then stabilized at a new elevated plateau level. The initial increase in [Ca2+]i consisted mainly of the release of sequestered Ca2+. The plateau phase was totally dependent on extracellular Ca2+. The influx of Ca2+ was blocked by Ni2+ and was decreased in depolarized cells. The importance of protein kinase C in regulating influx of Ca2+ was then evaluated. Addition of the phorbol ester 12-O tetradecanoylphorbol 13-acetate prior to thapsigargin significantly decreased the influx of extracellular Ca2+. Studies with bisoxonol to measure membrane potential showed that TPA depolarized the plasma membrane in FRTL-5 cells. In cells where protein kinase C was downregulated or was inhibited by staurosporine, the thapsigargin-induced influx of Ca2+ was enhanced. The results indicate that emptying intracellular Ca2+ pools is sufficient to induce influx of Ca2+ in FRTL 5 cells, and that protein kinase C has a modulatory effect on this process. PMID- 8452534 TI - Demonstration of adenosine deaminase activity in human fibroblast lysosomes. AB - Human fibroblast lysosomes, purified on Percoll density gradients, contain an adenosine deaminase (ADA) activity that accounts for approximately 10% of the total ADA activity in GM0010A human fibroblasts. In assays of lysosomal ADA, the conversion of [3H]adenosine into [3H]inosine was proportional to incubation time and the amount of lysosomal material added to reaction mixtures. Maximal activity was observed between pH 7 and 8, and lysosomal ADA displayed a Km of 37 microM for adenosine at 25 degrees C and pH 5.5. Lysosomal ADA was completely inhibited by 2.5 mM Cu2+ or Hg2+ salts, but not by other bivalent cations (Ba2+, Cd2+, Ca2+, Fe2+, Mg2+, Mn2+ and Zn2+). Coformycin (2.5 mM), deoxycoformycin (0.02 mM), 2'-deoxyadenosine (2.5 mM), 6-methylaminopurine riboside (2.5 mM), 2'-3' isopropylidene-adenosine (2.5 mM) and erythro-9-(2-hydroxy-3-nonyl)adenine (0.2 mM) inhibited lysosomal ADA by > 97%. In contrast, 2.5 mM S-adenosyl-L homocysteine and cytosine were poor inhibitors. Nearly all lysosomal ADA activity is eluted as a high-molecular-mass protein (> 200 kDa) just after the void volume on a Sephacryl S-200 column, and is very heat-stable, retaining 70% of its activity after incubation at 65 degrees C for 80 min. We speculate that compartmentalization of ADA within lysosomes would allow deamination of adenosine to occur without competition by adenosine kinase, which could assist in maintaining cellular energy requirements under conditions of nutritional deprivation. PMID- 8452535 TI - Kinetic behaviour of zymogen activation processes in the presence of an inhibitor. AB - A global kinetic analysis of a general zymogen activation model, where not only the activating but also the activated enzyme suffer an irreversible inhibition is presented. A reaction in which the enzyme acts upon a substrate is coupled to monitor the process. In addition, we determined the corresponding kinetic equations for a number of particular cases of the general model studied. Finally, a kinetic data analysis and a procedure to discriminate among the different mechanisms considered, which are based on the kinetic equations obtained, are suggested. PMID- 8452536 TI - Activation of human platelets by peroxovanadate is associated with tyrosine phosphorylation of phospholipase C gamma and formation of inositol phosphates. AB - Vanadate ions in the presence of H2O2 (peroxovanadate) induce a marked increase in the degree of tyrosine phosphorylation of proteins in human platelets. This increase preceded the onset of platelet shape change and aggregation, and is associated with activation of phospholipase C and increased [32P]phosphorylation of proteins of 47 kDa, a substrate for protein kinase C, and 20 kDa, a substrate for both myosin light-chain kinase and protein kinase C. The non-selective inhibitor of protein kinases, staurosporine, inhibits the increase in tyrosine phosphorylation of nearly all proteins and inhibits completely all other functional responses, suggesting that these events may be linked. In support of this, peroxovanadate stimulates tyrosine phosphorylation of phospholipase C gamma 1, suggesting that this may underlie its mechanism of platelet activation. Staurosporine also inhibited activation of phospholipase C by collagen, suggesting that tyrosine phosphorylation has an important role in the early stages of collagen-induced platelet activation. PMID- 8452537 TI - Protein kinase C-mediated phospholipase A2 activation, platelet-activating factor generation and prostacyclin release in spontaneously beating rat cardiomyocytes. AB - The expression of protein kinase C (PKC) isoenzymes and the effects of PKC activation on myocardial phospholipase A2 (PLA2) activity, platelet-activating factor (PAF) generation and eicosanoid release were studied in spontaneously beating cultured rat cardiomyocytes. Western blotting analysis indicated that these cells contain PKC alpha, beta, delta and zeta, but not PKC gamma or epsilon. Stimulation of cardiomyocytes with 4 beta-phorbol 12-myristate 13 acetate (PMA) led to a rapid increase in particulate-bound PKC activity, a response attributed to the activation of alpha-, delta- and zeta- type PKCs but not beta-type PKC. Translocation of PKC alpha, delta and zeta was accompanied by simultaneous increases in cellular lysophosphatidylcholine (lyso-PC), PAF, 15(S) hydroxy-5,8,-11,13-eicosatetraenoic acid (15-HETE), prostaglandin E2 (PGE2) and prostacyclin (PGI2) generation, suggesting that one or more of these isoenzymes directly or indirectly activates a PLA2 in these cells. Confirming this, 4 beta phorbol 12-monoacetate and 4 alpha-phorbol had no effect on cellular eicosanoid formation, while the PMA-induced response was fully abolished both in the presence of the PKC inhibitors staurosporine and CGP 41251 and in PKC-down regulated cells. PKC alpha, delta and/or zeta therefore appear to play an important role in the PMA-mediated activation of cardiomyocyte PLA2, an event leading to subsequent production of PGI2, PGE2, 15-HETE, lyso-PC and PAF in this tissue. PMID- 8452538 TI - Glucose transport activity and photolabelling with 3-[125I]iodo-4 azidophenethylamido-7-O-succinyldeacetyl (IAPS)-forskolin of two mutants at tryptophan-388 and -412 of the glucose transporter GLUT1: dissociation of the binding domains of forskolin and glucose. AB - The tryptophan residues 388 and 412 in the glucose transporter GLUT1 were altered to leucine (L) by site-directed mutagenesis and were transiently expressed in COS 7 cells. As assessed by immunoblotting, comparable numbers of glucose transporters were present in plasma membranes from cells transfected with wild type GLUT1, GLUT1-L388 or GLUT1-L412. Transfection of the wild-type GLUT1 gave rise to a 3-fold increase in the reconstituted glucose transport activity recovered from plasma membranes. In contrast, transfection of GLUT1-L412 failed to increase the reconstituted transport activity, whereas transfection of GLUT1 L388 produced only a 70% increase. Photolabelling of GLUT1-L412 with 3-[125I]iodo 4-azidophenethylamido-7-O-succinyldeacetyl (125IAPS)-forskolin was not different from that of the wild-type GLUT1, whereas the GLUT1-L388 incorporated 70% less photolabel than did the wild-type GLUT1. These data suggest a dissociation of the binding sites of forskolin and glucose in GLUT1. Whereas both tryptophan-388 and tryptophan-412 appear indispensable for the function of the transporter, only tryptophan-388 is involved in the binding of the inhibitory ligand forskolin. PMID- 8452539 TI - Cloning and expression of the bovine intestinal alkaline phosphatase gene: biochemical characterization of the recombinant enzyme. AB - A complete genomic clone and a full-length cDNA coding for bovine intestinal alkaline phosphatase have been isolated and sequenced. The gene (5.4 kb) contains 11 exons separated by ten small introns at positions identical to those other members of the eukaryotic tissue-specific alkaline phosphatase family. In addition, 1.5 kb of upstream sequences contain putative regulatory elements showing sequence similarity to human and mouse intestinal alkaline phosphatase promoter sequences. To achieve recombinant bovine intestinal alkaline phosphatase expression, the coding region of the gene was subcloned into the pcDNA I eukaryotic expression vector and transfected into Chinese hamster ovary cells. Recombinant bovine intestinal alkaline phosphatase displays enzymatic properties comparable with those of purified native bovine intestinal alkaline phosphatase, a slightly increased thermal stability and, upon desialylation, it shows a homogeneous behaviour in agarose gel electrophoresis and isoelectric focusing. The availability of the recombinant bovine intestinal alkaline phosphatase and the elucidation of its primary sequence will help to accelerate our efforts to obtain the first crystallographic model of a eukaryotic alkaline phosphatase molecule. PMID- 8452540 TI - Low-density lipoproteins are degraded in HepG2 cells with low efficiency. AB - In previous studies we have shown that in HepG2 cells, as compared with fibroblasts, the low-density lipoprotein (LDL) receptor is only weakly down regulated upon incubation of the cells with LDL. To explain this difference in down-regulation of the LDL-receptor activity, we studied simultaneously the intracellular processing of 125I-labelled LDL in both cell lines. Upon incubation of HepG2 cells with 125I-LDL, the appearance of degradation products started at 90 min, whereas in fibroblasts this lag time was only 30 min. The degradation efficiency (representing the ratio degradation/cell association of LDL) in HepG2 was less than 50% of that in fibroblasts up to 5h of incubation at 37 degrees C. The longer lag time and low efficiency of the degradation of LDL in HepG2 cells were independent of the cell density. Pulse-chase experiments indicated that the internalization rate of surface-bound LDL in HepG2 cells is similar to that of fibroblasts. Endosomal loading of 125I-LDL by incubation at 18 degrees C for 4.5 h, followed by a shift to 37 degrees C, resulted in degradation of LDL within 30 min in fibroblasts, whereas in HepG2 cells the lag time of the degradation was 90 min. In parallel experiments using subcellular fractionation by Percoll-gradient centrifugation of homogenized cells and 125I-tyramine-cellobiose-labelled LDL, we observed that in both cell types LDL is equally rapidly shifted from a low- to a high-density compartment (within 15 min), representing the endosomal and the late endosomal plus lysosomal compartment respectively. We conclude that in HepG2 cells the cell-bound LDL, upon internalization, goes through the intracellular itinerary at the same rate as in fibroblasts, but that either the fusion between late endosomes and lysosomes or the lysosomal degradation itself is proceeding at a lower efficiency. A low degradation rate of LDL may contribute to explain the relatively weak down-regulation of the LDL-receptor activity in HepG2 cells by LDL. PMID- 8452541 TI - The xylan-degrading enzyme system of Talaromyces emersonii: novel enzymes with activity against aryl beta-D-xylosides and unsubstituted xylans. AB - Talaromyces emersonii, a thermophilic aerobic fungus, produces a complete xylan degrading enzyme system when grown on appropriate substrates. In this paper we present the physicochemical and catalytic properties of three enzymes, xylosidase (Xyl) I (M(r) 181,000; pI 8.9), II (M(r) 131,000; pI 5.3) and III (M(r) 54,200; pI 4.2). Xyl I and II appear to be dimeric and Xyl III is a single-subunit protein. All three enzymes catalyse the hydrolysis of aryl beta-D-xylosides and xylo-oligosaccharides. Xyl I is a classic beta-xylosidase (1,4-beta-D-xylan xylohydrolase; EC 3.2.1.37), and Xyl II and III are novel xylanases (endo-1,4 beta-D-xylan xylanohydrolase; EC 3.2.1.8) which we believe have not hitherto been reported. In addition to the above substrates, they also catalyse the extensive hydrolysis of unsubstituted xylans, and may have considerable biotechnological potential. The hydrolysis product profiles and bond-cleavage frequencies with various substrates are presented. PMID- 8452542 TI - Photo-oxidation of 5-enolpyruvoylshikimate-3-phosphate synthase from Escherichia coli: evidence for a reactive imidazole group (His385) at the herbicide glyphosate-binding site. AB - Photo-oxidation of Escherichia coli 5-enolpyruvoylshikimate-3-phosphate synthase, a target for the non-selective herbicide glyphosate (N-phosphonomethylglycine), in the presence of pyridoxal 5'-phosphate resulted in irreversible inactivation of the enzyme. The inactivation followed pseudo-first-order and saturation kinetics with a Kinact. of 50 microM. The inactivation is specifically prevented by preincubation of the enzyme with the combination of shikimate 3-phosphate and glyphosate. Increasing glyphosate concentration during preincubation resulted in a decreasing rate of inactivation. On 95% inactivation, approximately one histidine per molecule of enzyme was oxidized. Tryptic mapping of the enzyme modified in the absence and presence of shikimate 3-phosphate and glyphosate as well as analyses of the histidine content in the isolated peptides indicated that His385, in the peptide Asn383-Asp-His-Arg386, was the site of oxidation. These results suggest that His385 is the most accessible reactive imidazole group under these conditions and is located close to the glyphosate-binding site. PMID- 8452543 TI - A structural role of the carotenoid in the light-harvesting II protein of Rhodobacter capsulatus. AB - The membrane-linked light-harvesting II protein (LHII) of Rhodobacter capsulatus was partly depleted of carotenoids by selective extraction with light petroleum. Carotenoid removal was accompanied by bleaching of the Qy(S1<--S0) absorption band of bacteriochlorophyll (Bchl) a near 800 nm, by a bathochromic shift and a broadening of the other Bchl Qy band at 850 nm, and by the formation of a weak Qy band of dissociated Bchl near 770 nm. The changes in the 800 and 850 nm bands seemed to reflect alterations in only those Bchl molecules that had lost their associated carotenoids, firstly, because the extent of the changes was closely correlated to the degree of carotenoid extraction, and, secondly, because the residual fraction of carotenoid-containing LHII, which could be almost quantitatively recovered from the membrane after detergent solubilization and ion exchange chromatography, showed an unmodified LHII absorption spectrum. The Bchl responsible for the shifted 850 nm band remained bound to protein, since its visible (Qx) transition seemed to retain the induced optical activity of the native bound pigment. Besides, the shifted Bchl could act as an efficient acceptor of singlet excitation energy from the pigments of the intact LHII fraction. The close similarity between the spectroscopic Bchl changes that accompany carotenoid extraction and the differential spectral features of carotenoidless LHII of Rhodobacter mutants, previously reported, strongly suggests that the direct cause of the spectral modifications is the absence of carotenoid and not any independent effect of the experimental manipulation of the membrane. Several interpretations of the structural changes that underlie the observed spectral changes are possible. The simplest one is to assume that carotenoid removal elicits an alteration in the angle between the Qy transition moments of two strongly interacting Bchl molecules. PMID- 8452544 TI - Nucleotide sequence and over-expression of morphine dehydrogenase, a plasmid encoded gene from Pseudomonas putida M10. AB - Pseudomonas putida M10 was originally isolated from factory waste liquors by selection for growth on morphine. The NADP(+)-dependent morphine dehydrogenase that initiates morphine catabolism is encoded by a large plasmid of 165 kb. Treatment of P. putida M10 with ethidium bromide led to the isolation of a putative plasmid-free strain that was incapable of growth on morphine. The structural gene for morphine dehydrogenase, morA, has been located on the plasmid by oligonucleotide hybridization, by coupled transcription-translation of cloned restriction fragments and by nucleotide sequence analysis and is contained within a 1.7 kb SphI fragment that has been cloned into Escherichia coli. The cloned dehydrogenase enzyme is expressed at high levels in E. coli resulting in a 65 fold increase in morphine dehydrogenase activity in cell-free extracts compared with P. putida M10. Morphine dehydrogenase was rapidly purified to homogeneity, as judged by SDS/PAGE, by a one-step affinity chromatography procedure on Mimetic Orange 3 A6XL. The properties of the purified enzyme were identical with those previously reported for P. putida M10 morphine dehydrogenase. The morA gene was sequenced and the deduced amino acid sequence confirmed by N-terminal amino acid sequencing of the over-expressed protein. The predicted amino acid sequence of morA, deduced from the nucleotide sequence, indicated that morphine dehydrogenase did not belong to the non-metal-requiring short-chain class of dehydrogenases, but was more closely related to the aldo-ketoreductases. PMID- 8452545 TI - Okadaic acid activates p42 mitogen-activated protein kinase (MAP kinase; ERK-2) in B-lymphocytes but inhibits rather than augments cellular proliferation: contrast with phorbol 12-myristate 13-acetate. AB - Ligation of the membrane immunoglobulin M receptor as well as stimulation with the protein kinase C agonist phorbol 12-myristate 13-acetate leads to a B lymphocyte proliferation and differentiation. Both stimuli activate p42 mitogen activated protein (MAP) kinase in human B-lymphocytes [Casillas, Hanekom, Williams, Katz and Nel (1991) J. Biol. Chem. 266, 19088-19094]. MAP kinase activation is dependent on tyrosine as well as threonine phosphorylation of the kinase and its activity is inhibited by tyrosine as well as threonine/serine phosphatases. Okadaic acid, a specific inhibitor of type 1 and 2A serine/threonine phosphatases, induced MAP kinase activity in a potent and dose dependent fashion, but failed to induce [3H]thymidine incorporation into normal human tonsil B-cells. Moreover, in combination with membrane immunoglobulin M ligation, okadaic acid decreased rather than increased [3H]thymidine incorporation. The kinetics of MAP kinase activation by okadaic acid differed from phorbol 12-myristate 13-acetate and anti-membrane immunoglobulin M stimulation. Okadaic acid induced tyrosine phosphorylation of 42 kDa and 44 kDa proteins which co-electrophoresed and co-chromatographed with ERK-2 and ERK-1 respectively. Ramos cells also contained a constitutively active 46 kDa MAP kinase which appeared as a separate peak in chromatography and could be immunoprecipitated by an antiserum against a rat ERK-1 fusion protein. PMID- 8452546 TI - Effects of exogenous insulin or vanadate on disposal of dietary triacylglycerols between mammary gland and adipose tissue in the lactating rat: insulin resistance in white adipose tissue. AB - The effects of exogenous insulin or vanadate (an insulin mimetic) on the disposal of dietary [14C]lipid between oxidation to 14CO2, deposition in adipose tissue or uptake by mammary gland and transfer to suckling pups were studied in virgin and lactating rats. After an oral load of [1-14C]triolein, virgin rats treated with a supraphysiological dose of insulin over 24 h showed a decrease (58%) in 14CO2 production and increased accumulation of [14C]lipid in carcass and white adipose tissue. There was a 2.5-fold increase in lipoprotein lipase activity in the latter. Chronic vanadate administration (12 days) had no effect on these parameters. In lactating rats, the stimulation of the deposition of [14C]lipid in adipose tissue by exogenous insulin was about 10% of that in virgin rats. In prolactin-deficient lactating rats there was no stimulation of [14C]lipid deposition in adipose tissue by insulin. However, both insulin and vanadate treatment increased the accumulation of [14C]lipid in mammary gland to the values seen in the mammary glands plus pups of normal lactating rats. Lipoprotein lipase activity in the gland was also restored to normal values. It is concluded that in lactation there is resistance to insulin stimulation of dietary lipid deposition in adipose tissue, and that this is not due to circulating prolactin. In addition, exogenous insulin plays a role in the regulation of lipoprotein lipase and hence of dietary lipid uptake into lactating mammary gland. PMID- 8452547 TI - UDP-sugar metabolism in Swarm rat chondrosarcoma chondrocytes. AB - UDP-sugars and adenine nucleotides were extracted from freshly isolated chondrocytes and primary cell cultures and analysed by anion-exchange h.p.l.c. The pool sizes of UDP-N-acetylglucosamine, UDP-N-acetylgalactosamine, UDP-glucose galactose, UDP-glucuronate and UDP-xylose were 2.9, 1.2, 2.5, 0.6 and 0.03 nmol/10(6) freshly isolated chondrocytes. When chondrocytes were maintained in Dulbecco's modified Eagle medium supplemented with 15% foetal-bovine serum, synthesis of [35S]proteoglycan and [3H]protein decreased over the first 48 h in culture, as did the pools of UDP-glucuronate and ATP. In contrast, the size of the UDP-N-acetylhexosamine pools underwent little change during culture. [35S]Proteoglycan and [3H]protein syntheses were stimulated in cultures supplemented with serum or insulin compared with those maintained in medium alone, in agreement with previous results. However, the UDP-sugar pool sizes were the same in both supplemented and non-supplemented cultures. In cultures maintained in the presence of [1-3H]glucose, the UDP-sugars were labelled to a constant 3H specific radioactivity which was very similar to that of the labelling medium. UDP-N-acetylhexosamines were labelled to constant 3H specific radioactivity with [6-3H]glucosamine as a precursor, but only about 1 in 375 of these UDP-sugars was derived from the amino sugar in the presence of glucose. The half-life (t1/2) for UDP-hexoses, UDP-glucuronate and UDP-N-acetylhexosamines was about 12, 12 and 50 min respectively. PMID- 8452548 TI - Molecular interconversion of cold-sensitive cytosolic 3,3',5-tri-iodo-L-thyronine binding proteins from human erythrocytes: effect of cold, heat and pH treatments. AB - Cytosolic 3,3',5-tri-iodo-L-thyronine-binding proteins (CTBP I, II and IV species) from human red blood cells undergo rapid loss of activity at low temperatures. Cold treatment of CTBPs was accompanied by dissociation of the polymeric protein to the 60 kDa inactive monomer. Re-activation of the cold inactivated CTBP IV by warming resulted in association of the monomer to the active polymeric form. A similar association-dissociation phenomenon was also obtained isothermically, though pH changes. We conclude that CTBP I and CTBP II are polymeric forms of CTBP IV. PMID- 8452549 TI - The existence of multiple tetrameric conformers of chicken liver pyruvate carboxylase and their roles in dilution inactivation. AB - The time-dependent loss of enzymic activity and tetrameric structure of chicken liver pyruvate carboxylase (EC 6.4.1.1) after dilution below 2 units/ml was apparently monophasic and first-order. When examined over a range of initial enzyme concentrations, both activity and tetrameric structure decayed to equilibrium levels which were dependent on the initial concentration. The observed rate constants for the loss of enzymic activity (i) showed no apparent dependence on the initial enzyme concentration, and (ii) were of similar magnitude to the corresponding rate constants of dissociation. Computer simulations of the most likely kinetic model suggest that the predominant form of the dissociated enzyme is the monomer. Dilution of pyruvate carboxylase in the presence of the allosteric activator acetyl-CoA largely prevented the subsequent dissociation of the tetrameric molecule. In addition, acetyl-CoA was able to cause a degree of activation and reassociation when added after dilution inactivation had been allowed to occur. Electron-microscopic observation showed the treatment with avidin before dilution markedly decreased the degree of dissociation of the enzyme tetramer. This structure-stabilizing effect of avidin was dependent on preincubation of the concentrated enzyme solution with acetyl CoA. We propose that, over a range of protein concentrations, the tetrameric enzyme exists in two forms that are in equilibrium, and that acetyl-CoA alters the equilibrium to favour the more compact form. PMID- 8452550 TI - Snake venom cardiotoxin can rapidly induce actin polymerization in intact platelets. AB - The action of Taiwan cobra (Naja naja atra) venom cardiotoxin on rabbit platelets at 37 degrees C was characterized by observing cytoskeletal alterations and cell lysis. At a concentration of 21.4 microM the toxin produced no cell lysis within 30 s, and less than 5% of the total lactate dehydrogenase activity of intact cells was detected in the suspending medium after the interaction had proceeded for 3 min. The extent of cell lysis was proportional to toxin concentration and interaction time. Before cell lysis, the toxin caused rapid incorporation of actin monomers into cross-linked actin filaments. The actin incorporation could be inhibited by either the presence of cytochalasin B or increased CaCl2 concentration in the suspending medium. However, addition of indomethacin did not influence the toxin-induced cytoskeletal change. PMID- 8452551 TI - Multiple pseudouridine synthase activities for small nuclear RNAs. AB - The formation of pseudouridine (psi) in human U1, U2 and U5 small nuclear RNAs (snRNAs) was investigated using HeLa cell extracts. Unmodified snRNAs were synthesized in vitro and the extent of psi formation was determined after incubation in cell extracts. The formation of psi on labelled substrates was monitored in the presence of 5-fluorouracil (5-FU)-containing snRNAs as inhibitors of psi formation. The conversion of uridine to psi was inhibited only when the cognate 5-FU-containing inhibitor snRNA was included in the reaction. For example, 5-FU-containing U1 RNA inhibited psi formation in unmodified U1 RNA, but not in (unmodified) U2 or U5 RNAs. The results suggest that there are at least three activities that form psi in these snRNAs. The 5-FU-containing RNAs were stable during incubation in the cell extracts. A 12-fold molar excess of unlabelled U1 RNA did not inhibit psi formation on a labelled U1 RNA substrate, whereas a 3-fold molar excess of 5-FU-containing U1 RNA nearly abolished psi formation on the U1 substrate. The fact that 5-FU-containing snRNAs are potent inhibitors of psi formation in these pre-mRNA splicing cofactors raises the possibility that this is related to the cytotoxicity of fluoropyrimidines in cancer chemotherapy. PMID- 8452552 TI - Proteolytic modification of the heparin-binding affinity of extracellular superoxide dismutase. AB - The heparin-binding affinity of the tetrameric extracellular superoxide dismutase (EC-SOD) is a result of the cooperative effect of the heparin-binding domains of the subunits, located in the hydrophilic, strongly positively charged C-terminal ends. EC-SOD C, the high-heparin-affinity type, exposed to immobilized trypsin and plasmin was found to rapidly lose its affinity for heparin, without any loss of enzymic activity or major change in molecular mass as judged by size-exclusion chromatography. Heparin and dextran sulphate 5000 inhibited the proteolysis, suggesting that EC-SOD C sequestered by heparan sulphate proteoglycan in vivo is partially protected against proteolysis. The loss of heparin-affinity occurred with the stepwise formation of intermediates, and the pattern upon chromatography on heparin-Sepharose and subsequent immunoblotting was compatible with the notion that the changes are due to sequential truncations of heparin-binding domains from subunits composing the EC-SOD tetramers. A similar pattern with intermediates and apparent truncations has previously been found with EC-SOD of human plasma. The findings show that the unique design of the heparin-binding domain of EC-SOD allows easy modification of the heparin-affinity by means of limited proteolysis, and suggest that such proteolysis is a major contributor to the heterogeneity in heparin-affinity of EC-SOD in mammalian plasma. PMID- 8452553 TI - From lung hypersensitivity to bronchial hyperreactivity. What can we learn from studies on animal models? PMID- 8452554 TI - Binding of the radioligand [35S]adenosine 5'-O-(2-thiodiphosphate) and intracellular calcium response in rat liver parenchymal cells. AB - The use of the radioligand [35S]adenosine 5'-O-(2-thiodiphosphate) (ADP beta 35S) for the determination of P2y-purinoceptors on turkey erythrocyte membranes has recently been described. In the present study, we were able to demonstrate specific binding of this radioligand in intact rat liver parenchymal cells. Within 10 min a thermodynamic equilibrium was obtained which lasted for 25 min with a subsequent decline. Displacement studies with several nucleotides were performed yielding Ki values of 1.5 +/- 0.47 microM for UTP, 1.8 +/- 0.35 microM for adenosine 5'-O-(2-thiodiphosphate) (ADP beta S), 31 +/- 6.2 microM for ATP and 35 +/- 6.1 microM for GTP. In addition, we showed that ADP beta 35S is highly resistant to degradation by ecto-nucleotidases, with only 14.5 +/- 1.4% of total ADP beta 35S present being degraded after 1 hr, and that the binding of ADP beta 35S to its binding sites was modulated by EDTA. The Ki value of ATP shifted to 8.1 +/- 1.2 microM upon the addition of 1 mM EDTA to the incubation medium. In these rat liver parenchymal cells all nucleotides promoted calcium entry in a dose-dependent manner with EC50 values of 3.5 +/- 0.22 microM for UTP, 20.7 +/- 3.1 microM for ATP, 38.3 +/- 6.4 microM for ADP beta S and 73.6 +/- 13.7 microM for GTP, with GTP being a partial agonist. Based on the data derived from the present study we discuss the possible correlation between binding and functional experiments and conclude that the described receptor resembles most closely the P2u-purinoceptor and/or "nucleotide receptor", in that UTP is at least as active as ATP. PMID- 8452555 TI - Differential effects of metabolic inhibitors on cellular and mitochondrial uptake of organic cations in rat liver. AB - The effects of several metabolic inhibitors on the uptake of tri-n butylmethylammonium (TBuMA) were studied in isolated rat liver mitochondria, isolated rat hepatocytes and isolated perfused rat livers, in order to characterize further the mechanisms for carrier-mediated uptake and cellular accumulation of organic cations in the liver. Treatment of isolated hepatocytes with valinomycin, carbonylcyanide-m-chlorophenyl-hydrazone (CCCP), dinitrophenol, oligomycin or antimycin resulted in a rapid decrease in cellular ATP within 3 min of addition. The initial uptake rate of TBuMA was generally largely affected by these treatments. However, fructose at 10 mM had no effect at all on the uptake rate of the cation whereas cellular ATP was decreased to an extent comparable to that after treatment with the metabolic inhibitors. Consequently it was hypothesized that the metabolic inhibitors affected the initial cellular uptake rate of organic cations due to either altered intracellular sequestration (e.g. mitochondria) or alternatively to direct effects on the plasma membrane rather than by decreasing cellular ATP. Isolated rat mitochondria were shown to take up organic cations very efficiently. Accumulation in this organelle is probably driven by the negative membrane potential as measured by the uptake of the lipophilic cation [3H]tetraphenylphosphonium. Treatment of the isolated mitochondria with various metabolic inhibitors decreased the membrane potential in parallel to the effects on the uptake of TBuMA. Since mitochondria constitute a considerable intracellular volume, they may contribute largely to the storage of the organic cation in the hepatocyte. In isolated perfused livers, preloaded with either TBuMA or tetraphenylphosphonium (TPP+), the addition of valinomycin or CCCP leads to a marked backflux of the cations from the liver into the perfusion medium. This suggests strongly that a large part of the intracellular storage capacity is lost after metabolic inhibitor treatment, probably as the consequence of dissipation of the mitochondrial membrane potential. Since the metabolic inhibitors in contrast to TBuMA uptake did not decrease the initial uptake rate of TPP+ into isolated hepatocytes, it was concluded that mitochondrial uptake (mitochondria are the major storage sites for TPP+) is not an essential determinant of the initial uptake rate in intact hepatocytes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8452556 TI - Relaxation of rat thoracic aorta by N-nitroso compounds and nitroprusside and their modifications of nucleic acid bases through release of nitric oxide. AB - Nitroprusside and two newly synthesized direct-acting mutagens, N-nitroso-2 fluorenylactamide and N-nitroso-dinitroacetaminophen, were able to elicit the concentration-dependent relaxation of rat aorta. The vascular responses could be antagonized by hemoglobin that binds nitric oxide with high affinity and by methylene blue which inhibits soluble guanylate cyclase activity. We used four bases in DNA as the substrates to test the capacity to deaminate of the two compounds. Xanthine, hypoxanthine and uracil as well as some unusual bases such as 8-OH-adenine and 8-OH-guanine were found. These findings suggest that both the muscle relaxation and mutagenicity of these two compounds might be due to the release of nitric oxide in living cells. PMID- 8452557 TI - In vitro inhibition of carnitine acyltransferase activity in mitochondria from rat and mouse liver by a diethylhexylphthalate metabolite. AB - The effects of mono(2-ethyl-5-oxohexyl)phthalate [ME(O)HP], a di(2 ethylhexyl)phthalate (DEHP) metabolite and a potent peroxisomal inducer, on the mitochondrial beta-oxidation were investigated. In isolated rat hepatocytes, ME(O)HP inhibited long chain fatty acid oxidation and had no effect on the ketogenesis of short chain fatty acids, suggesting that the inhibition occurred at the site of carnitine-dependent transport across the mitochondrial inner membrane. In rat liver mitochondria, ME(O)HP inhibited carnitine acyltransferase I (CAT I; EC 2.3.1.21) competitively with the substrates palmitoyl-CoA and octanoyl-CoA. An analogous treatment of mouse mitochondria produced a similar competitive inhibition of palmitoyl-CoA transport whereas ME(O)HP exposure with guinea pig and human liver mitochondria revealed little or no effect. The addition of clofibric acid, nafenopin or methylclofenopate revealed no direct effects upon CAT I activity. Inhibition of transferase activity by ME(O)HP was reversed in mitochondria which had been solubilized with octyl glucoside to expose the latent form of carnitine acyltransferase (CAT II), suggesting that the inhibition was specific for CAT I. Our results demonstrate that in vitro ME(O)HP inhibits fatty acid oxidation in rat liver at the site of transport across the mitochondrial inner membrane with a marked species difference and support the idea that induction of peroxisome proliferation could be due to an initial biochemical lesion of the fatty acid metabolism. PMID- 8452558 TI - Primary and secondary oxidative metabolism of dextromethorphan. In vitro studies with female Sprague-Dawley and Dark Agouti rat liver microsomes. AB - The O-demethylation of dextromethorphan (DM) to dextrorphan (DR) is catalysed by the polymorphic CYP2D6 (cytochrome P4502D6) isozyme in man. DM is commonly used as a probe for phenotyping subjects as either poor or extensive metabolizers for the debrisoquine/sparteine oxidative polymorphism via CYP2D6. The enzyme kinetics of DM O- and N-demethylation, and the N- and O-demethylations of the primary metabolites DR and 3-methoxymorphinan (3MM), respectively, were studied in liver microsomes from female Dark Agouti (DA) rats, the poor metabolizer counterpart, and female Sprague-Dawley (SD) rats, the extensive metabolizer counterpart. The formation of metabolites was quantified by HPLC with fluorescence detection and kinetic parameters were calculated. The intrinsic clearance (Vmax/Km) of the O demethylation of 3MM to 3-hydroxymorphinan (3OHM) was 180-fold lower in DA rats (0.11 vs 20.77 mL/hr/mg) due to a 60-fold higher Km (108.7 vs 1.76 microM) and 3 fold lower Vmax (11.5 vs 35.95 nmol/mg/hr). The kinetics for DR N-demethylation to 3OHM did not differ between rat strains. The Michaelis-Menten constant (Km) for DM N-demethylation to 3MM was similar between SD and DA rats (85.04 vs 68.99 microM); however, SD rats displayed a 2-fold higher Vmax (83.37 vs 35.49 nmol/mg/hr) and intrinsic clearance (0.96 vs 0.51 mL/hr/mg). The O-demethylation of DM to DR in SD rats showed a high and low affinity enzyme component, with the high affinity intrinsic clearance contributing 98% of the total intrinsic clearance in these rats. DM O-demethylation in DA rats was characterized by a single enzyme system. The high affinity O-demethylating enzyme in SD rats showed a 20-fold lower Km (2.5 vs 55.6 microM) and a three-fold higher Vmax (51.04 vs 16.84 nmol/mg/hr) resulting in a 66-fold higher intrinsic clearance (20.04 vs 0.31 mL/hr/mg) compared to DA rats. Quinine, dextropropoxyphene, (+/-)methadone and (+/-)propafenone were shown to be potent inhibitors of 3MM and DM O demethylation but did not inhibit DR or DM N-demethylation at similar concentrations. SD and DA rats showed a clear strain difference in 3MM O demethylation and DM O-demethylation. In contrast, DR N-demethylation and DM N demethylation do not appear to be under genetic control in the female SD-DA rat model. Kinetic parameters and inhibition studies suggest that 3MM and DM O demethylation pathways in the rat may be mediated by the same cytochrome P450 isozyme. PMID- 8452559 TI - N-acetylcysteine ameliorates hyperoxic lung injury in the preterm guinea pig. AB - The therapeutic efficacy of N-acetylcysteine (NAC) in the management of hyperoxia induced lung injury was assessed using the preterm guinea pig model of prematurity. Preterm guinea pig pups were delivered by Caesarean section 3 days preterm, and exposed to either 21 or 95% oxygen for 72 hr. NAC (200 mg/kg body weight) or saline was injected twice daily. Bronchoalveolar lavage fluid (BALF) from hyperoxia-exposed pups contained significantly higher protein concentrations and an increased number of neutrophils. NAC partly ameliorated lung injury, preventing the increase in BALF protein concentration, which is generally associated with oedema. There was no effect on the movement of neutrophils into the lung airspaces in response to oxygen. Treatment with NAC had no effect on lung or liver glutathione (reduced) (GSH) concentrations either after 2 hr post administration, or over the full 72 hr experimental period. An apparent resistance of the lung to increased synthesis or uptake of GSH was demonstrated by the lack of effect of direct administration of GSH, its isopropyl ester or 2 oxo-4-thiazolidine carboxylic acid. Oxygen exposure alone (95%) increased lung concentrations by 60-70%. It would, therefore, appear from this data that NAC may have potential as a future component of antioxidant therapy, although its effects are not mediated through increased GSH levels. PMID- 8452560 TI - Human liver microsomal cytochrome P450 3A isozymes mediated vindesine biotransformation. Metabolic drug interactions. AB - Vindesine biotransformation was investigated using a bank of human liver microsomes. The drug was converted into one major metabolite (M) upon incubation with the microsomes. Large interindividual variations were observed: vindesine biotransformation rates ranged from 1.2 to 12.9 pmol/min/mg protein. Vindesine metabolic processes followed Michaelis-Menten kinetics: Km = 24.7 +/- 9.4 microM, Vmax = 1.5 +/- 0.8 nmol/min/mg protein. The involvement of human cytochrome P450 3A isozymes in vindesine metabolism was demonstrated by: (1) competitive inhibition of vindesine biotransformation by compounds known to be specifically metabolized by human cytochrome P450 3A. Apparent Ki values were 3.6, 17.9 and 19.8 microM for quinidine, troleandomycin and erythromycin, respectively; (2) immunoinhibition of vindesine metabolism by polyclonal anti-P450 3A antibody; (3) significant correlation between immunoquantified P450 3A and vindesine biotransformation (r = 0.800, P < 0.001); and (4) significant correlation between erythromycin N-demethylase activity, which was supported by P450 3A in humans, and vindesine biotransformation (r = 0.853, P < 0.001). Other vinca alkaloids also exerted an inhibitory effect on vindesine biotransformation with apparent Ki values of 3.8, 10.6 and 19.2 microM for vinblastine, vincristine and navelbine, respectively, suggesting a possible involvement of the same cytochrome subfamily in their hepatic metabolism. Moreover, a number of anticancer drugs currently associated with the vinca alkaloids, such as teniposide, etoposide, doxorubicin, lomustine, folinic acid and mitoxantrone, significantly inhibited vindesine biotransformation. PMID- 8452561 TI - Effects of ether anaesthesia and fasting on various cytochromes P450 of rat liver and kidney. AB - Fed and fasted, male, Wistar albino rats exposed to light ether anaesthesia and killed immediately or after 30 or 120 min recovery were compared with non anaesthetized rats for changes in liver and kidney cytochrome P450 (CYP) activities. In fed rats, liver total CYP (nmol/mg protein) decreased by 30% immediately after ether, but was restored to normal levels after 30 min recovery; in fasted rats, liver total CYP increased by 20% by fasting alone, then decreased by 65% immediately after ether, and recovered to only 70% of control at 2 hr after ether. Rat liver cytochrome P4501A (CYP1A; 7-ethoxyresorufin O-deethylase or EROD activity) and cytochrome P4502B (CYP2B; 7-pentoxyresorufin O-dealkylase or PROD activity) were decreased after ether anaesthesia, similar to those for total CYP. In contrast, rat liver cytochrome P4502E1 (CYP2E1), determined by p nitrophenol hydroxylation, increased by 40% by ether anaesthesia alone, 70% by fasting alone and 140% by ether plus fasting; these increases were confirmed by the CYP2E1-mediated activation of nitrosopyrrolidine and by immunoblot analysis using antibody to CYP2E1. In rat kidney, losses of total CYP, CYP1A and CYP2B, and increases of CYP2E1, induced by ether anaesthesia, were much more marked in fasted (90% loss in total CYP, 30% increase in CYP2E1) than in fed rats (slight loss in total cytochrome P450, 30% increase in CYP2E1). As maximum losses of total CYP in liver of fasted rats exposed to ether occurred at the time of maximum increase of CYP2E1 and maximum rate of generation of reactive oxygen species (ROS), it is suggested that the increase of CYP2E1, resulting from its stabilization by fasting and ether, leads to generation of ROS, increase in lipid peroxidation and consequent loss of total CYP, associated with the hepatic and renal necrosis seen in ether intoxication and surgical trauma. PMID- 8452562 TI - Effect of dexamethasone on the peptic activity of gastric lumen and mucosa. AB - Dexamethasone (9 alpha-fluoro-16 alpha methyl-11 beta,17 alpha,21-trihydroxy-1,4 pregnadiene-3,20-dione-21-phosphate), a synthetic glucocorticoid, has a dual role on pepsinogen content of the gastric lumen and mucosa as measured by its peptic activity. Following stimulation the luminal peptic activity gradually decreases after 6 hr, then returns to basal levels at 18 hr and by 24 hr is inhibited by 50%. The luminal peptic activity induced by the secretory compound mercaptomethylimidazole (MMI) is also decreased. Dexamethasone effect on both basal and MMI-induced peptic activity can be reproduced by cycloheximide or puromycin, translational blockers of protein synthesis. This drug also has an independent time and dose-dependent inhibitory effect on gastric mucosal peptic activity which does not correlate with increased peptic activity of the lumen. Dexamethasone appears to be more effective than hydrocortisone and corticosterone in inhibiting the basal peptic activity of both lumen and mucosa. The inhibitory effect of this drug on tissue peptic activity is not mediated through induction of any inhibitory protein as evidenced by the insensitivity of the effect to actinomycin D. Studies on [14C]phenylalanine incorporation into gastric protein indicate that the effect of dexamethasone on tissue pepsinogen content is not due to a generalized block of protein synthesis. PMID- 8452563 TI - Partial purification and characterization of a rat liver polychlorinated biphenyl (PCB) binding protein. AB - A protein capable of specifically binding polychlorinated biphenyls (PCB) was partially purified from rat liver cytosol. After labeling with [3H]2,2',4,4',5,5' hexachlorobiphenyl (6-CB), protein enrichment was guided by monitoring the protein-bound radioactivity through a sequence of purification steps including ion exchange chromatography and preparative gel electrophoresis. In addition, specific binding tests of individual fractions were carried out. An average 100 fold enrichment of the 40 kDa protein was achieved. A variety of ligands were tested in competitive binding studies with 6-CB. Whereas penta- and hexachloro PCB congeners are high affinity competitors, the 3,3',4,4'-tetrachlorobiphenyl congener does not compete for 6-CB binding. Studies on the species and tissue distribution suggest a prevalence of the binding protein in tissues of the rat. Since the natural physiological ligand of the protein has not yet been identified, the function of the protein can only be speculated on. PMID- 8452564 TI - Allopurinol transport in human erythrocytes. AB - The mechanism of allopurinol [4-hydroxypyrazolo(3,4-d)pyrimidine] transport into human erythrocytes was investigated with an inhibitor stop assay. Allopurinol transport could be resolved into two components: (1) a saturable system and (2) a non-saturable process, which most likely represents non-facilitated diffusion. Allopurinol transport had a Km of 268 mumol/L and a Vmax of 28 pmol/microL intracellular volume/sec; the non-saturable component was 0.0195/sec. Mutual inhibition studies showed that the competitive Ki values of hypoxanthine and adenine on allopurinol transport were 120 and 3 mumol/L, respectively. These Ki values as well as the IC50 values of 100-150 mumol/L for hypoxanthine and 3-10 mumol/L for adenine were similar to the corresponding transport Km values of these bases, which are 128 and 8 mumol/L, respectively. The Ki of allopurinol on hypoxanthine transport was 274 mumol/L and thus nearly identical to its Km. Thus in erythrocytes the uricostatic agent allopurinol is an alternative substrate for the purine transport system, but lacks the exceptional high affinity it has for xanthine oxidase. This could explain the paradoxical clinical side effect of allopurinol, namely that it can provoke an attack of gout. Theophylline, a methylated purine, inhibited allopurinol transport with an IC50 of 200-400 mumol/L. Oxypurinol [4,6-dihydroxypyrazolo(3,4-d)pyrimidine], the main metabolite of allopurinol, also inhibited allopurinol transport with an IC50 of 20-40 mumol/L. This is noteworthy, since allopurinol and oxypurinol do not share the same transport system in the kidney. PMID- 8452565 TI - Cytochrome P450 isoforms in human fetal tissues related to phenobarbital inducible forms in the mouse. AB - Four polyclonal antibodies raised against purified mouse liver cytochrome P450s representing Cyp1a, Cyp2a, Cyp2b and Cyp2c subfamilies were used to detect their related forms in human adult and fetal tissues. In immunoblot analysis, anti Cyp2c antibody detected two to three proteins in adult livers and one to three proteins in 70% of the 18 fetal livers studied. Anti-Cyp2a-5 antibody recognized a 50-kDa protein in 50% of the fetal adrenals. Anti-Cyp1a-2 antibody reacted with a single protein (55 kDa) in adult liver. The anti-Cyp2b-10 antibody did not detect proteins in any of the tissues. No proteins were detected in fetal kidneys. There was no coumarin 7-hydroxylase activity (COH) in fetal liver or adrenals. The 7-ethoxycoumarin O-deethylase (ECOD) activities were slightly higher in fetal adrenals (mean 6.1 pmol/mg protein/min) vs livers. The fetal adrenal ECOD activity was not inhibited by the anti-Cyp2a-5 antibody. Aryl hydrocarbon hydroxylase (AHH) activities in fetal livers were about 5% of those in adult livers. AHH activity in fetal liver was not inhibited by the anti-Cyp2c antibody. Testosterone 6 beta-hydroxylase activity was much lower in fetal liver than in adult liver (about 20 and 1700 pmol/mg protein/min, respectively). No immunoinhibition occurred in fetal adrenal progesterone hydroxylation, hepatic benzphetamine N-demethylation and hepatic ethylmorphine N-demethylation. These data suggest that members of the P450 subfamilies 1A, 2A and 2B are expressed at a very low level in fetal liver, and that fetal liver may contain members of the 2C subfamily. PMID- 8452566 TI - Hepatocellular uptake of peptides--I. Carrier-mediated uptake of hydrophilic linear peptides with renin inhibitory activity into isolated rat liver cells. AB - The hepatic uptake of a hydrophilic, cationic linear peptide with renin inhibitory activity [5(4-amino-piperidyl-1-carbonyl)-L-2,6[3H]phenyl-alanyl-beta alanyl-(4S- amino-3S-hydroxy-5-cyclohexyl)-pentan-carbonyl-L-isoleucyl-amin ome thyl-4-amino-2-methyl-pyrimidine-citrat] (code number EMD 56133; EMD, E. Merck, Darmstadt) was investigated in isolated rat hepatocytes. EMD 56133 was taken up by isolated rat liver cells in a time-, concentration-, energy- and temperature dependent manner. The uptake was a combination of diffusion and a carrier mediated process. EMD 56133 was accumulated 4.5-fold in liver cells. Eighty-three per cent of the accumulated peptide was found in the cytosol, not bound to membrane proteins. Seventeen per cent was associated with membrane proteins after cell fractionation and centrifugation at 100,000 g. The permeability coefficient of the non-saturable uptake of EMD 56133 was P = 1.973 x 10(-6) cm/sec. The kinetic constants for the carrier-mediated transport are Km = 92 microM and Vmax = 128 pmol/mg x min. Various substrate analogs inhibited the uptake of EMD 56133. AS-30D ascites hepatoma cells and Reuber hepatoma cells did not accumulate EMD 56133. The absence of oxygen or a decreased cellular ATP content blocked the hepatocellular uptake of the renin inhibitor. Temperatures above 20 degrees increased the transport; the activation energy was determined to be Aapp = 41 kJ/mol. The apparently active uptake of EMD 56133 was not sodium dependent. In contrast, the membrane potential might be a driving force for the transport of the positively charged EMD 56133. PMID- 8452567 TI - Hepatocellular uptake of peptides--II. Interactions between hydrophilic linear renin-inhibiting peptides and transport systems for endogenous substrates in liver cells. AB - To define the endogenous transport system responsible for the hepatocellular uptake of hydrophilic linear peptides, interactions between the cationic renin inhibitor, [5(4-amino-piperidyl-1-carbonyl-L-2,6[3H]phenyl-alanyl-beta-alanyl(4S- amino-3S-hydroxy-5-cyclo-hexyl)-pentan-carbonyl-L-isoleucyl-ami nom ethyl-4-amino 2-methyl-pyrimidine-citrat] (code number EMD 56133; EMD, E. Merck, Darmstadt) and substrates of endogenous transport systems of liver cells were studied in isolated rat hepatocytes. EMD 56133 competitively inhibited the uptake of ouabain (Ki = 75 microM) and vice versa (Ki = 200 microM). In contrast, the sodium dependent as well as the sodium-independent uptake of cholate and the total uptake of taurocholate were non-competitively blocked, whereas EMD 56133 decreased the uptake of the cyclosomatostatin 008 in an uncompetitive manner. EMD 56133 did not interfere with transport systems for monovalent organic cations, amino acids and long chain fatty acids. The uptake of rifampicin, however, was increased in the presence of EMD 56133. The transport of EMD 56133 was non competitively inhibited by cholate (Ki = 126 microM) and taurocholate (Ki = 44 microM), and uncompetitively inhibited by the linear peptide EMD 51921. In contrast, the uncharged compound ouabain (Ki = 200 microM) and the bivalent organic cation d-tubocurarine (Ki = 370 microM) competitively inhibited the uptake of the renin inhibitor. Several substrates of other endogenous transport systems (e.g. bilirubin, cyclopeptides, monovalent cations, dipeptides, amino acids, fatty acids, hexoses) did not interfere with the transport of EMD 56133. Our results suggest that transport systems for bivalent organic cations or uncharged compounds (ouabain) are able to eliminate the linear hydrophilic peptide tested. PMID- 8452568 TI - An investigation into the role of reactive oxygen species in the mechanism of 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity using neuronal cell lines. AB - The study of oxygen radical generation and effects during 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) metabolism was undertaken in an in vitro test system. Three neurochemically discrete neuronal cell lines, B50 (cholinergic) and B65 rat cell lines and SKNSH human neuroblastoma (both catecholaminergic), were exposed to MPTP (0-200 microM). Parallel experiments were performed using reagent H2O2, an intermediate which may be generated during MPTP metabolism, to determine whether MPTP and H2O2 had any selectivity of toxicity and whether the mechanisms of cell death were similar. MPTP toxicity was shown to be reduced by monoamine oxidase B inhibitors, pargyline (P < 0.01) and selegiline (P < 0.05), indicating that toxicity was due to metabolism of MPTP rather than the parent compound. Cytotoxicity was also decreased in the presence of antioxidants, most notably in the presence of superoxide dismutase and catalase together (P < 0.01), suggesting that reactive oxygen species (ROS) play a role in MPTP-induced cell death. Attempts to determine the intracellular target for oxidative attack did not identify significant levels of lipid peroxidation products, but did demonstrate nucleoid expansion, possibly the result of double stranded DNA breaks induced by ROS. PMID- 8452569 TI - Acetaldehyde-induced formation of 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3 carboxylic acid in rats. AB - 1-Methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (MTCA) is one of the metabolites of peak E substance, which, based on epidemiological studies, has been thought to be a possible causative agent of the tryptophan-induced eosinophilia-myalgia syndrome. Acute ethanol and L-tryptophan administration in rats pretreated with cyanamide resulted in the formation of MTCA. Concentrations of MTCA were estimated at 27 ng/g in blood and 33 ng/g in kidneys. Chronic treatment with a liquid diet containing ethanol as 36% of the total calories for 6 weeks increased these levels. MTCA was barely observed in rats that had received acute or chronic ethanol in the absence of cyanamide, or in the cyanamide-tryptophan controls. Cyanamide facilitation of ethanol-dependent MTCA biosynthesis may be due to a potentiation of the blood level of acetaldehyde derived from ethanol. The blood acetaldehyde level in rats that had been acutely treated with cyanamide, ethanol and L-tryptophan was 348 microM, and averaged 503 microM in rats that received the same treatment after chronic consumption of ethanol. In contrast to the above findings, L-tryptophan intake promoted the formation of 1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (TCCA) in rats. This is the first report of MTCA in mammalian tissue during tryptophan and ethanol metabolism. PMID- 8452570 TI - Regulatory effects of zinc and copper on the calcium transport system in rat liver nuclei. Relation to SH groups in the releasing mechanism. AB - In isolated hepatic nuclei, the heavy metals Zn2+ and Cu2+ (10 microM) inhibited Ca2+ uptake and caused a prompt release of Ca2+ from preloaded nuclei in a concentration-dependent manner, with Zn2+ being more effective than Cu2+. The sulfhydryl group reducing agent dithiothreitol (DTT) protected the nuclei from the effects of heavy metals; DDT (1 mM) almost completely blocked Zn(2+)- or Cu(2+)-induced Ca2+ release and inhibition of Ca2+ uptake. The sulfhydryl modifying reagent N-ethylmaleimide (NEM; 0.2 mM) also caused Ca2+ release, but it did not have an appreciable effect on Ca2+ uptake. Furthermore, in the presence of NEM heavy metals did not evoke Ca2+ release. The present study demonstrates that Zn2+ and Cu2+ have a stimulatory effect on Ca2+ release from isolated rat liver nuclei, and that the SH group may play an important role in the Ca(2+) releasing mechanism in liver nuclei. PMID- 8452571 TI - Direct observation of a fluorinated anticonvulsant in brain tissue using 19F-NMR techniques. AB - A fluorinated derivative of an anticonvulsant gamma-butyrolactone [alpha-(1,1 difluoroethyl)-alpha-methyl-gamma-butyrolactone; alpha-DFGBL] was synthesized as a probe for NMR spectroscopic observation of the drug in brain tissue. The fluorinated compound is an efficacious anticonvulsant in mice, and inhibits the specific binding of [35S]t-butylbicyclophosphorothionate ([35S]TBPS) to mouse brain membranes with a concentration dependence similar to that of the non fluorinated compound alpha-ethyl-alpha-methyl-gamma-butyrolactone. Quantitative 19F-NMR spectroscopic studies, coupled with chromatographic measurements of drug tissue concentration, showed that virtually all of the alpha-DFGBL in brain was NMR-observable and that, following intraperitoneal injection, alpha-DFGBL rapidly achieved millimolar concentrations in brain. The 19F-NMR spectra of a alpha-DFGBL in brain and liver tissue were broad (1-2 ppm) and complex, exhibiting multiple chemical shift features. The major chemical shift features in these spectra were assigned on the basis of differential extraction and comparison of 19F spin-spin relaxation times (T2s) and 19F chemical shifts of alpha-DFGBL in tissue to those in pure solvents. The major feature at 10.4 ppm in the tissue spectra was assigned to a weakly polar, membrane-associated environment for the fluorinated compound, while the feature at 11.2 ppm was assigned to an aqueous environment for alpha-DFGBL. The drug was in slow exchange between these two environments in brain. In addition, the feature at lowest field (9.7-9.8 ppm) was identified as a water-soluble hydroxy-acid metabolite of alpha-DFGBL produced by the liver. These data indicate that gamma-butyrolactone anticonvulsants achieve high concentrations in brain, where they exist in several, largely membrane associated, environments. These findings are consistent with the purported action of the gamma-butyrolactones as low-affinity modulators of gamma-aminobutyric acid A channels. PMID- 8452572 TI - Criteria for the identification of non-redox inhibitors of 5-lipoxygenase. AB - Methoxyalkyl thiazoles have been identified as a novel series of selective 5 lipoxygenase inhibitors with anti-inflammatory properties (Bird et al., J Med Chem 34: 2176-2186, 1991). Based on their structure, it was proposed that the potency of these compounds is not due to redox or iron-chelating properties. In the studies reported here, it was found that the model compounds 1-[3-(naphth-2 ylmethoxy)phenyl]-1-(thiazol-2-yl)propy l methyl ether (ICI 211965) and 3-[1-(4 chlorobenzyl)-4-methyl-6-(5- phenylpyridin-2-ylmethoxy)-4,5-dihydro-1H thiopyrano[2 ,3,4-c,d]indol-2- yl]-2,2-dimethylpropanoic acid (L-689,065) (1) are inactive as reducing substrates in the 5-lipoxygenase-catalyzed decomposition of lipid hydroperoxides, (2) inhibit the 5-lipoxygenase-catalyzed reaction of reducing agents with lipid hydroperoxides, and (3) strongly inhibit the turnover dependent inactivation of 5-lipoxygenase. These three observations with ICI 211965 and L-689,065 are in contrast to the behavior of other potent 5 lipoxygenase inhibitors from other structural classes, such as L-670,630, BW A4C, and zileuton, which all function as reducing substrates for 5-lipoxygenase. The data indicate that methoxyalkyl thiazoles and thiopyranoindoles are reversible dead-end inhibitors of 5-lipoxygenase and that the effects of inhibitors on the pseudoperoxidase activity and rate of enzyme inactivation provide simple tests to distinguish between redox and non-redox inhibitors of 5-lipoxygenase. PMID- 8452573 TI - A randomized, controlled trial of arthroscopic surgery versus closed-needle joint lavage for patients with osteoarthritis of the knee. AB - OBJECTIVE: To compare arthroscopic surgery and closed-needle joint lavage for patients with non-end-stage osteoarthritis (OA) of the knee under controlled, experimental conditions. METHODS: Thirty-two subjects who met specific clinical, radiologic, medical, and rehabilitation criteria were randomized to receive arthroscopic surgery (n = 18) or joint lavage (n = 14). Outcome measures evaluated at baseline and at 3 and 12 months of followup included 3 standard clinical parameters, self-reported pain and functional status (by the Arthritis Impact Measurement Scales), 50-foot walk time, 2 global scales, and direct and indirect medical costs. RESULTS: At 3 months of followup, there were no significant between-group differences in pain, self-reported and observed functional status, and patient and "blinded" physician global assessments. The arthroscopic procedure cost $3,840 more than did closed-needle joint lavage. After 1 year, there were no between-group differences in medication costs, utilization of medical services, or indirect costs related to employment or use of household help. After 1 year, 44% of subjects who underwent arthroscopy reported improvement and 58% of subjects who underwent joint lavage improved. Patients with tears of the anterior two-thirds of the medial meniscus or any lateral meniscus tear had a higher probability of improvement (by "blinded" physician assessment) after arthroscopic surgery (0.63) than did patients with other intraarticular pathology (0.20). CONCLUSION: The search for and removal of soft tissue abnormalities via arthroscopic surgery does not appear justified for all patients with non-end-stage OA of the knee who fail to respond to conservative therapy, but it may be beneficial for certain subgroups. PMID- 8452574 TI - The relative toxicity of disease-modifying antirheumatic drugs. AB - OBJECTIVE: To compare the toxicities of commonly employed disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA). METHODS: Toxicity Index scores, computed from symptoms, laboratory abnormalities, and hospitalizations attributable to DMARD therapy, were assessed in 2,747 patients with RA receiving 3,053 courses of 6 DMARDs and 1,309 courses of prednisone over 7,278 patient-years. Results were adjusted for severity of illness and other covariates. RESULTS: Least toxic was hydroxychloroquine (mean +/- SEM score 1.38 +/- 0.15), followed by intramuscular gold (2.27 +/- 0.17) and the closely grouped D-penicillamine (3.38 +/- 0.36), methotrexate (3.82 +/- 0.35), and azathioprine (3.92 +/- 0.39). Auranofin (5.25 +/- 0.32) was most toxic, but this toxicity resulted from a high frequency of minor complications. Hospitalizations because of auranofin or hydroxychloroquine therapy were not noted. Prednisone (3.83 +/- 0.39) was of comparable toxicity, although it is likely that not all events of prednisone toxicity were captured. For reference, the toxicity of methotrexate and azathioprine was similar to that of the most toxic nonsteroidal antiinflammatory drugs (NSAIDs) (indomethacin 3.99, tolmetin sodium 3.96, and meclofenamate 3.86). Hydroxychloroquine showed less toxicity than the most commonly used prescription NSAIDs. CONCLUSION: There are substantial differences in toxicity among DMARDs and less important differences in toxicity between specific DMARDs and specific NSAIDs. PMID- 8452575 TI - Chlorambucil. An effective corticosteroid-sparing agent for patients with recalcitrant dermatomyositis. AB - OBJECTIVE: To investigate the effectiveness of oral chlorambucil treatment in patients with dermatomyositis (DM) that is recalcitrant to treatment with prednisone and/or immunosuppressive agents. METHODS: Five patients with recalcitrant DM were treated with oral chlorambucil, 4 mg/day, after discontinuation of the other immunosuppressive agent (azathioprine or methotrexate). Three patients were treated with a combination of prednisone and chlorambucil, and 2 with chlorambucil alone. RESULTS: Beneficial effects were noted within 4-6 weeks in all 5 patients, and corticosteroids were eventually discontinued in 4. Currently, only 1 patient is still receiving therapy; the other 4 have stopped chlorambucil after 13-30 months of treatment, and their disease remains in remission. Minimal chlorambucil toxicity was noted, consisting of leukopenia in 2 patients. CONCLUSION: Our findings suggest that chlorambucil is an effective, corticosteroid-sparing agent for the control of DM. PMID- 8452576 TI - Chlorambucil in the treatment of patients with immune-mediated rheumatic diseases. PMID- 8452577 TI - Determinants of serious liver disease among patients receiving low-dose methotrexate for rheumatoid arthritis. AB - OBJECTIVE: To assess the risk of serious liver disease in patients with rheumatoid arthritis (RA) taking methotrexate (MTX). METHODS: We surveyed members of the American College of Rheumatology to determine previous use of MTX in the treatment of rheumatoid arthritis and to identify cases of cirrhosis and liver failure. Cases were confirmed by review of pathology specimens, findings from diagnostic testing, and clinical presentations. A case-control study was then conducted to ascertain prognostic factors. Case and control medical records were reviewed for information on MTX therapy as well as other possible determinants of serious liver disease. RESULTS: Twenty-four cases of cirrhosis and liver failure were identified, giving a 5-year cumulative incidence of approximately 1/1,000 treated patients. Six of the 24 patients had died: 4 died of the initial liver disease, 1 of hepatic complications of another illness, and 1 of unrelated causes. Two patients continue to have active liver disease. Late age at first use of MTX and duration of therapy with MTX were independent predictors of serious liver disease. CONCLUSION: Serious liver disease is an uncommon, age- and dose related complication of low-dose MTX therapy for RA. PMID- 8452578 TI - Antirheumatic drugs: a proposed new classification. PMID- 8452579 TI - Preliminary criteria for the classification of Sjogren's syndrome. Results of a prospective concerted action supported by the European Community. AB - OBJECTIVE: Different sets of diagnostic criteria have been proposed for Sjogren's syndrome (SS), but none have been validated with a large series of patients or in a multicenter study. We conducted the present study involving 26 centers from 12 countries (11 in Europe, plus Israel), with the goals of reaching a consensus on the diagnostic procedures for SS and defining classification criteria to be used in epidemiologic surveys and adopted by the scientific community. METHODS: The study protocol was subdivided into two parts. For part I, questionnaires regarding both ocular and oral involvement were developed; they included 13 questions and 7 questions, respectively. For part II a limited set of diagnostic tests was selected, and the exact procedure to be followed in performing these tests was defined. Part I of the study included 240 patients with primary SS and 240 age- and sex-matched controls. Two hundred forty-six patients with primary SS, 201 with secondary SS, 113 with connective tissue diseases but without associated SS, and 133 control patients were studied in part II. RESULTS: The study resulted in (a) the validation of a simple 6-item questionnaire for determination of dry eyes and dry mouth, which showed good discriminant power between patients and controls, to be used in the initial screening for sicca syndrome; and (b) the definition of a new set of criteria for the classification of SS. The sensitivity and specificity of the criteria in correctly identifying patients with either the primary or the secondary variant of SS were also determined. CONCLUSION: Using the findings of this prospective multicenter European study, general agreement can be reached on the diagnostic procedures to be used for patients with SS. Final validation of the preliminary classification criteria for SS is underway. PMID- 8452580 TI - Clinical, serologic, and immunogenetic studies in childhood-onset systemic lupus erythematosus. AB - OBJECTIVE: To determine the frequency of systemic lupus erythematosus (SLE) associated clinical manifestations, autoantibodies, and HLA class II alleles in a large cohort of patients with childhood-onset SLE. METHODS: Eighty children with SLE onset before age 18 (27 before age 11) were studied for the frequency of renal, neuropsychiatric, and hematologic complications as well as for anti-native DNA, Ro, La, Sm, and U1 RNP autoantibodies. HLA-DR, DQ, and DP alleles were determined by oligotyping. The results were compared with findings in 213 adults with SLE onset at or after age 18 years. RESULTS: Renal involvement was more frequent in those with childhood-onset SLE, especially those with onset before age 11 (82%, compared with 53% in adults). Anti-U1 RNP was more common in American blacks with SLE onset before age 18. HLA-DRB1*0301, DQA1*0501, DQB1*0201 was more common in Caucasians and DRB1*1503, DRB5*0101, DQA1*0102, DQB1*0602 in American blacks, regardless of age at SLE onset. Anti-Sm autoantibodies were most highly associated with HLA-DQA1*0102 and DQB1*0602. CONCLUSION: While childhood onset SLE shares many immunogenetic and serologic similarities to adult-onset disease, important clinical differences nevertheless exist in children with this disease. PMID- 8452581 TI - Limited prognostic value of changes in antineutrophil cytoplasmic antibody titer in patients with Wegener's granulomatosis. AB - OBJECTIVE: To assess the correlation and prognostic value of antineutrophil cytoplasmic antibody (cANCA) titers with disease activity in patients with Wegener's granulomatosis (WG). METHODS: One hundred six patients with WG had serum ANCA determinations; 72 had serial titers obtained routinely at 1-3-month intervals. One hundred twelve subjects (19 of whom were healthy donors) served as controls. All serum samples were tested for cANCA by an indirect immunofluorescence technique. A prospective analysis of disease activity and cANCA values was performed. Disease activity was assessed according to clinical, laboratory, radiographic, and histopathologic findings. RESULTS: Positivity for cANCA was a sensitive (88%) marker of active WG. However, changes in serial titers temporally correlated with a change in disease status in only 64% of patients. Furthermore, an increase in the cANCA titer preceded clinical exacerbation of disease in only 24% of patients who had been in remission or had low-grade, smoldering disease. CONCLUSION: A rise in cANCA titer alone should not be considered adequate evidence of an impending clinical exacerbation, and therefore does not justify initiating or increasing immunosuppressive therapy. PMID- 8452582 TI - The measurement of collagenase, tissue inhibitor of metalloproteinases (TIMP), and collagenase-TIMP complex in synovial fluids from patients with osteoarthritis and rheumatoid arthritis. AB - OBJECTIVE: To compare the levels of collagenase, tissue inhibitor of metalloproteinases (TIMP), and collagenase-TIMP complex in synovial fluid (SF) from patients with rheumatoid arthritis (RA) and patients with osteoarthritis (OA). This study aims to clarify existing data from previously used enzyme or inhibitor activity assays performed following separation by gel filtration, by using a 1-step enzyme-linked immunosorbent assay (ELISA) for each component. METHODS: Total collagenase, free TIMP, and collagenase-TIMP complex were measured using a newly developed, specific double-antibody sandwich ELISA: RESULTS: Levels of both collagenase and TIMP were significantly higher in RA patients (collagenase 1,560 +/- 150 ng/ml [mean +/- SEM], TIMP 1,610 +/- 130 ng/ml; n = 80) than OA patients (collagenase 420 +/- 90 ng/ml, TIMP 1,050 +/- 60 ng/ml; n = 80), with the difference being especially striking for collagenase. Sixteen RA fluids had detectable levels of collagenase-TIMP complex, compared with only 3 OA fluids. CONCLUSION: The level of total collagenase in SF is greater in RA than OA, while levels of free TIMP show more overlap between the 2 diseases; this may simply reflect the increased inflammation seen in RA, or it may reflect a different disease mechanism. PMID- 8452583 TI - Allotypic dependency of the specificity and avidity of human monoclonal IgM rheumatoid factors derived from rheumatoid synovial cells. AB - OBJECTIVE: To better understand the genetic derivation and pathogenicity of rheumatoid factor (RF) molecules in rheumatoid arthritis (RA), we have focused our studies on rheumatoid synovial cells (RSC). METHODS: Five monoclonal human IgM rheumatoid factor (mRF)-secreting hybridomas were produced from the RSC of an RA patient. Fine subclass specificities and avidities of these RSC mRFs were compared with several paraprotein monoclonal IgM RFs using direct binding (reactivity) and competitive inhibition (specificity and avidity) enzyme-linked immunosorbent assays. RESULTS: The following observations were made: 1) RSC mRF had greater avidity for IgG than did paraprotein mRF; 2) 4 of the 5 RSC RF were highly avid for IgG3; and, 3) the avidity of RSC RF binding for IgG3 was highest for IgG molecules expressing the G3m(5) allotype. CONCLUSION: We conclude that RSC RF have different specificities and avidities than do paraprotein RF. This may suggest an antigen-driven process in RA synovium, with the production of higher-avidity IgG3m(5)-specific RSC RF, which could have special pathogenetic importance. PMID- 8452584 TI - Assessment of clinical competence of medical students by using standardized patients with musculoskeletal problems. AB - OBJECTIVE: To assess medical students' clinical competence in addressing musculoskeletal problems. METHODS: Nineteen junior medical students completed 2 standardized patient-based tests structured to capture their clinical decisions from undiagnosed chief complaint to management. RESULTS: No student approached the highest possible score on either test, and the students as a group received less than half the possible points on 5 important aspects of diagnostic reasoning. CONCLUSION: Standardized patient-based tests can be structured to provide enlightening information about medical students' clinical competence with regard to musculoskeletal problems. PMID- 8452585 TI - Early-onset osteoarthritis linked to the type II procollagen gene. Detailed clinical phenotype and further analyses of the gene. AB - OBJECTIVE: To specify in detail the clinical phenotype in 2 Finnish families demonstrating linkage between the type II procollagen gene (COL2A1) and osteoarthritis (OA). We also reevaluated the linkage and screened the exon sequences of the COL2A1 gene for mutations. METHODS: We used single-stranded conformation polymorphism and denaturing gradient-gel electrophoresis techniques for the analyses. RESULTS: The patients' phenotype represented typical, but early onset, OA. There was no clinical or radiographic evidence of chondrodysplasia. No mutation in the protein-coding regions of the COL2A1 gene could be identified. However, the linkage analysis with a new multiallelic marker resulted in a statistically more significant logarithm of odds (LOD) score than has been reported. CONCLUSION: Familial OA with classic clinical and radiographic findings is tightly linked to the COL2A1 gene. Systematic screening of the 54 exons did not, however, reveal any mutations; this suggests that the mutation may lie in the promoter region or within the introns of this 35-kb gene. PMID- 8452586 TI - Localized scleroderma progressing to systemic disease. Case report and review of the literature. AB - We describe a 15-year-old girl with biopsy-proven morphea who developed progression to systemic disease 2 years after initial presentation. In contrast to other reported patients with localized scleroderma, some of whom have had mild, nonprogressive systemic involvement, this patient developed severe, debilitating disease, with skin tightness, sclerodactyly, esophageal involvement, restrictive pulmonary disease, and myopathy. From the time of her initial evaluation, the patient was positive for antinuclear antibodies (ANA), which were shown to be primarily directed against the Ku antigens. This observation suggests that ANA may be a prognostic indicator for progression to systemic disease. PMID- 8452587 TI - Primary systemic amyloidosis masquerading as giant cell arteritis. Case report and review of the literature. AB - Amyloidosis is a rare disease in which a fibrillar protein is deposited in multiple human tissues. Of the 4 subtypes, the most common type involving rheumatic disease features is hemodialysis-associated amyloidosis. Herein we describe an elderly man who presented with symptoms of giant cell arteritis or systemic vasculitis and was found to have amyloidosis as demonstrated on muscle, nerve, and temporal artery biopsy. PMID- 8452588 TI - Skeletal muscle lymphoma in patients with the acquired immunodeficiency syndrome: a diagnostic challenge. PMID- 8452589 TI - Fluorescent light photosensitivity in patients with systemic lupus erythematosus: comment on the article by Rihner and McGrath. PMID- 8452590 TI - DQB*0301 in Felty's syndrome. PMID- 8452591 TI - Statement on Haemophilus influenzae type b conjugate vaccines for use in infants and children. PMID- 8452592 TI - From FPC to FHSA to ... health commission? PMID- 8452593 TI - Interictal and postictal focal hypermetabolism on positron emission tomography. AB - Decreased glucose utilization in the epileptogenic zone is typically observed interictally on positron emission tomography (PET), whereas ictal PET studies reveal complex patterns of increased and decreased metabolism. PET findings of 7 children, ages 2 months to 16 years, are described and demonstrate small focal regions of hypermetabolism in the absence of clinical or electrographic seizure during the 2-deoxy-2[18F]fluoro-D-glucose (FDG) uptake period. Magnetic resonance imaging scans were nonlocalizing in 5 of 7 children. In 4 children, seizures had not occurred for at least several hours prior to PET. Electroencephalography during PET disclosed active spike-and-wave activity on the side of interictal hypermetabolism in these 4 children. The remaining 3 children had seizures within 15 min prior to FDG injection and were considered postictal; their PET images revealed focal hypermetabolism. Results indicated the need for electroencephalographic monitoring during functional neuroimaging studies of all epileptic patients. The biochemical basis of interictal hypermetabolism is probably related to increased energy consumption by an active epileptogenic focus, whereas postictal hypermetabolism is likely due to energy expenditure for the restoration of resting membrane potentials and chemical homeostasis following an epileptic event. PMID- 8452594 TI - Guillain-Barre syndrome in childhood: natural course and efficacy of plasmapheresis. AB - Eight children with Guillain-Barre syndrome were treated with plasmapheresis. Retrospective comparisons were made with 11 historic control patients. Eight children required mechanical ventilation, 4 of whom were in the plasmapheresis group. One week after the last plasmapheresis treatment, patients receiving plasmapheresis within 7 days of symptom onset had improved by one Guillain-Barre syndrome score. Discharge Guillain-Barre syndrome scores were significantly lower for those receiving plasmapheresis (P < .05). Patients in the plasmapheresis group had a decrease in the number of days of mechanical ventilation, time until motor recovery, and overall cost. Our results are consistent with published literature and indicate that plasmapheresis for childhood Guillain-Barre syndrome is a safe and effective treatment to shorten the time to recovery. PMID- 8452595 TI - Hemimegalencephaly: evaluation with positron emission tomography. AB - We performed positron emission tomographic (PET) studies with 2-deoxy 2[18F]fluoro-D-glucose in 8 children with hemimegalencephaly (HME). HME is a developmental brain malformation associated with epilepsy, hemianopsia, and varying degrees of developmental delay. We hypothesized that the relatively poor overall developmental outcome of surgically hemispherectomized HME patients as a group, compared to children undergoing hemispherectomy for Sturge-Weber syndrome or chronic focal encephalitis, is related to dysfunction of the structurally "normal" non-HME side and that PET would be helpful in the pre-surgical evaluation of HME patients with intractable epilepsy. Visual analysis of the non HME side on PET clearly revealed evidence of cortical hypometabolism in 4 patients compared to controls. Seven children underwent epilepsy surgery. One child had a glucose metabolic pattern suggesting a cortical lamination defect in the non-HME hemisphere, bilateral independent seizure onset, and was not considered to be a surgical candidate. We found a general correlation between the pattern of glucose utilization in the less affected hemisphere and prognosis. Although the follow-up periods are short, it is recommended that HME children with intractable epilepsy undergo hemispherectomy in the first year of life in order to allow maximal brain plasticity to occur; however, preoperative evaluation should also include an assessment of the integrity of the non-HME hemisphere. PMID- 8452596 TI - Nature, time-course, and extent of cerebral edema in perinatal hypoxic-ischemic brain damage. AB - To ascertain the nature, time-course, and extent of the cerebral edema that accompanies perinatal hypoxic-ischemic brain damage, 7-day postnatal rats were subjected to unilateral right common carotid artery ligation followed by exposure to hypoxia with 8% oxygen for up to 3 hours. Some rat pups were sacrificed during hypoxia-ischemia or recovery for determination of cerebral hemispheric water content and percentage of brain swelling. Other animals were sacrificed and their brains processed either for determination of cerebral cortical edema and infarct volume or for horseradish peroxidase staining. The results indicated that cerebral edema occurs even during the course of hypoxia-ischemia and that the extent and duration of edema formation during the recovery period is dependent upon the severity of tissue injury. The data also disclosed a direct, linear correlation between infarct volume and the extent of cerebral edema. Accordingly, the greater the severity of cerebral edema, the proportionately greater the extent of infarction. Horseradish peroxidase staining, a reflection of vasogenic edema, occurred in 17 of 19 brains in a distribution which corresponded closely to the distribution of neuropathologic alterations observed histologically. The findings indicate that cerebral edema can occur in the absence of consequent infarction and that when infarction does occur, the associated edema contributes little or nothing to the severity of the ultimate brain damage. PMID- 8452597 TI - Diagnosis of dystrophinopathies: review for the clinician. AB - The dystrophinopathies are muscle disorders due to an abnormality of an Xp21 linked gene which produces the dystrophin protein. The most common of these disorders are the Duchenne and Becker muscular dystrophies. Modern molecular genetic techniques enable reliable diagnosis and prognosis in many patients, but there are occasional pitfalls. Furthermore, the clinical spectrum of the dystrophinopathies are now such that the clinician needs to be aware of a broader range of clinical disorders that require analysis of the dystrophin gene and its product, not just those that mirror a classic Duchenne or Becker muscular dystrophy picture. This spectrum ranges from a severe form presenting at birth to asymptomatic elevation of CK. Females may be manifesting carriers or present as a severe phenotype when the abnormal gene is expressed as an X-autosome translocation or monosomy X. Laboratory diagnosis and prognosis can be made most accurately by using both DNA analysis at the dystrophin gene and immuno-analysis of muscle with antibodies directed against different regions of the protein product. This review describes some exemplary patients, suggests a clinical classification for dystrophinopathies, and outlines a diagnostic approach. PMID- 8452598 TI - Infantile idiopathic myopathic carnitine deficiency: treatment with L-carnitine. AB - A series of 9 infants, ranging in age from 3 months to 5 years (average: 2 years), suffered from idiopathic myopathic carnitine deficiency presenting as hypotonia and motor delay. Secondary carnitine deficiency was eliminated by appropriate tests. Muscle carnitine concentration ranged from 2.3-7.1 nmol/mg non collagen protein (NCP; average: 4.87 nmol/mg NCP; normal: 22 +/- 6 nmol/mg NCP). Lipid accumulation in muscle was observed in 2 of 8 patients. Therapy with L carnitine (100 mg/kg/day in most patients) was given with clinical and laboratory follow-up 6 months later. In 7 of 9 patients, muscle tone and motor function improved. Muscle carnitine concentration increased to a range of 2.7-23.4 nmol/mg (average: 12.27 nmol/mg). In some patients the muscle carnitine content multiplied by a factor of 3-4, but carnitine concentration reached the normal range in only 2 patients. Most infants with idiopathic carnitine deficiency did benefit from 6 months of therapy; however, in order to achieve full recovery the duration of therapy should probably continue for longer periods, with a dose of not less than 100 mg/kg/day. PMID- 8452599 TI - Timing of brain insults in severe neonatal encephalopathies with isoelectric EEG. AB - In a neonatal intensive care unit of a large obstetric hospital, 20 neonates (7 preterm, 9 term, 4 postterm) with at least one isoelectric recording were treated over a 6-year period. Seventy-four EEGs were obtained in this cohort, including 36 isoelectric recordings. Seven infants in this group had evidence of a predominant antepartum component of a pathologic process based on placental, postmortem examination findings, or clinical history. Of the 16 placentas available for review, chronic lesions were observed in 13 of 16 specimens, including villitis, infarction, dysmaturity, and thrombosis. Seven of 9 patients with postmortem neuropathologic examinations had evidence of chronic lesions, principally neuronal necrosis, infarction, and microcalcifications. An additional 10 infants had evidence of an antepartum contribution to a pathologic process that continued into either the intrapartum or neonatal periods, based on maternal and/or neonatal medical factors. Clinical findings supportive of antepartum insults included intrauterine growth retardation, antepartum hemorrhage, abnormal antepartum fetal heart rate patterns, and maternal medical complications. Three patients had either intrapartum- or neonatal-onset of injury. Clinical signs of severe encephalopathy, however, were present in the immediate postnatal period in most patients (18 of 20; 90%). Assessment of clinical and pathologic information on neonates with isoelectric EEGs may estimate the timing of brain injury to the antepartum period, as opposed to, or in addition to, the labor and delivery periods. A neonate who suffered brain injury before parturition may be neurologically depressed after birth with absence of electrocerebral activity on EEG. PMID- 8452600 TI - Neuropathologic study of newborns with prenatal-onset leukomalacia. AB - The distribution of leukomalacia and glial fibrillary acidic protein (GFAP) positive glial cells in prenatal- and postnatal-onset leukomalacia were compared and diagnosed histologically in 128 autopsied infants and the different pathogeneses were examined. Prenatal-onset leukomalacia was diagnosed in 12 of 71 still-births and neonates surviving less than 3 days (16.9%). All 4 preterm infants of less than 32 gestational weeks had widespread white matter necrosis and 4 of 5 term infants had focal necrosis. GFAP-positive glial cells were more increased in the deep and intermediate white matter in both forms of leukomalacia than in the controls, although in the subcortical white matter they were less increased in prenatal- than postnatal-onset leukomalacia. These differences may indicate different pathogeneses, including vascular maturity and causal factors, in prenatal- and postnatal-onset leukomalacia. PMID- 8452601 TI - Progressive juvenile segmental spinal muscular atrophy. AB - Juvenile segmental spinal muscular atrophy (JSSMA) typically involves the distal upper extremities and follows a benign course over 2-4 years then stabilizes. We report 2 males who presented in their teens with insidious distal upper extremity atrophy and weakness as in typical JSSMA but who then progressed to involvement of the lower extremities and hyperreflexia. There was no sensory loss. Electromyography and muscle biopsy demonstrated features consistent with localized anterior horn cell dysfunction. These patients are noteworthy because they demonstrate that some patients with JSSMA also may have involvement of the lower limbs several years after initial presentation. Progressive JSSMA may be categorized in the clinical spectrum between the spinal muscular atrophies and amyotrophic lateral sclerosis. PMID- 8452602 TI - Leigh disease presenting as Guillain-Barre syndrome. AB - A 4-year-old male evidenced the criteria for the diagnosis of Guillain-Barre syndrome. Eventually a diagnosis of Leigh disease was made based on magnetic resonance imaging and mitochondrial enzyme deficiencies. Although chronic neuropathy has been reported with Leigh disease, this is the first reported patient with acute symmetric motor polyneuropathy. PMID- 8452603 TI - Membranous nephropathy associated with multiple sclerosis. AB - Membranous nephropathy and multiple sclerosis are believed to be mediated by immune mechanisms. A patient is reported with the first described association of membranous nephropathy and multiple sclerosis. Its significance and possible pathogenetic mechanisms are discussed. PMID- 8452604 TI - Childhood stroke associated with protein C or S deficiency and primary antiphospholipid syndrome. AB - Two girls, 22 months and 12 years of age, presented with repeated cerebral infarctions in association with primary antiphospholipid syndrome. The younger patient also suffered from protein C deficiency, while the other one had protein S and complement C4 deficiencies. All other causes of cerebral infarction were excluded; however, vasculitis remains a possibility in one patient. Both girls developed spastic tetraparesis as a sequela of the previous infarctions. The two patients were treated with aspirin and prednisone, with remission of the infarctions during the next 8 months of observation. A primary deficiency of protein C or S is proposed which would produce cerebral thrombosis with exposure of phospholipids; this thrombosis then, like antigens, would generate antibodies acting on the thrombin-thrombomodulin complex, exacerbating the thrombotic process. The association of complement C4 deficiency is an additional risk factor. PMID- 8452605 TI - Mobius syndrome in infant exposed to cocaine in utero. AB - The pathophysiology of Mobius syndrome has been debated for decades. A vascular etiology is currently favored because it explains the wide clinical spectrum of this syndrome. An infant is reported who was born with Mobius syndrome after a pregnancy complicated by heavy maternal use of cocaine and alcohol. We speculate that cocaine-induced vasoconstriction at a critical time of cerebrovascular development produced a vascular disruption sequence leading to the Mobius syndrome. PMID- 8452606 TI - Isolated angiitis of CNS: treatment with pulse cyclophosphamide. AB - A 12-year-old boy with a history of "migraine" headache presented with an increasingly severe headache accompanied by emesis and unsteadiness. Evaluation revealed an acute cerebral hemorrhage with subsequent angiographic studies demonstrating multiple areas of segmental narrowing in both the anterior and posterior cerebral circulations. He was diagnosed with isolated angiitis of the central nervous system and high-dose steroid therapy was administered to which he responded for 6 months. Symptoms recurred and repeat angiography demonstrated persistent segmental narrowing. Pulse cyclophosphamide therapy was begun with resolution of symptoms and normalization of angiography following 6 treatments. Although rare in children, isolated angiitis of the central nervous system can occur in children and aggressive immunosuppression should be considered as the mode of therapy. PMID- 8452607 TI - Early defibrillation in out-of-hospital sudden cardiac death: an Australian experience. AB - All patients with primary cardiac disease presenting with out-of-hospital sudden cardiac death (OH-SCD) to a provincial hospital were reviewed retrospectively over a 5-year period from 1985 to 1989. This coincided with the introduction of out-of-hospital defibrillation (OH-DEFIB) by ambulance officers. Of 215 patients, 17 (9%) survived to leave hospital alive, 15 of whom underwent OH-DEFIB. There was an increase in survivors from 4%, prior to OH-DEFIB, to 9% of all cardiac arrests, but this was not statistically significant (P = 0.3). However, long term survival amongst immediate survivors was associated with a statistically significant improvement following the introduction of OH-DEFIB (15 of 30 (50%) vs. 2 of 19 (10.5%), P < 0.01). Mean call-out, at-scene and transfer times did not significantly vary between survivors and non-survivors. A total of 155 (72%) had a known cardiac history, with the majority (74%) of arrests occurring at home. Of 134 witnessed arrests, only 46 (34%) underwent bystander-initiated cardiopulmonary resuscitation (CPR). A programme in CPR aimed at relatives of known cardiac patients, and the adoption of a paramedic protocol which improves oxygenation at the time of arrest are recommended. PMID- 8452608 TI - Prospective audit of the pattern, severity and circumstances of injury sustained by vehicle occupants as a result of road traffic accidents. AB - The pattern and severity of injuries sustained by 174 vehicle occupants consecutively admitted to the Accident and Emergency Department of the Edinburgh Royal Infirmary were prospectively documented. Drivers (DR) accounted for 66% of the patients, 20% were front seat passengers (FSP) and 14% were rear seat passengers (RSP). Injured patients were more likely to be male, young, intoxicated and not wearing a seat-belt. The position of the patient within the vehicle at the time of the accident and point of impact significantly affected the pattern of injury sustained. The majority of injuries were sustained by the upper body and the pattern of injury is discussed. Most accidents occurred at low speeds and higher speeds were associated with an increased severity of injury. Seat-belts reduced the overall severity of injuries, in particular those to the face and chest, but may increase the risk of neck injury. Head-rests do not appear to influence the incidence of neck injury. Clinically apparent alcohol intoxication was associated with a markedly increased risk of severe injury. PMID- 8452609 TI - Sternal fracture--a modern review. PMID- 8452610 TI - Telephoned head injury referrals: the need to improve the quality of information provided. AB - The decision to transfer a patient with a head injury to a neurosurgical department is usually made during a referral telephone call. The referring doctor describes the patient's condition to the neurosurgeon who then decides whether or not the patient needs to be transferred. Failure to inform the neurosurgeon adequately, may result in a disastrous decision to transfer an unstable patient. Alternatively, a patient who needs urgent neurosurgical care may not be transferred. This study assessed the information volunteered by 50 doctors referring head-injured patients. Extra information obtained on request was recorded separately. The referring doctor often failed to provide important information. For example, only 17 doctors volunteered the pulse rate, 16 the blood pressure and six the respiratory rate. Furthermore, the Glasgow Coma Scale was under-used and apparently not understood properly. This may hinder the decision to transfer a patient. A standard referral data sheet is recommended. PMID- 8452611 TI - Transthecal digital block. AB - Transthecal digital nerve block is performed by a palmar percutaneous injection of local anaesthetic into the flexor tendon sheath. Total analgesia of the digit is achieved rapidly. This technique was carried out on 46 patients in the accident and emergency department. Successful anaesthesia was obtained in 45 patients. There were no complications. PMID- 8452612 TI - The introduction of automatic blood pressure monitoring to an accident & emergency resuscitation room. AB - Machines for automatic non-invasive blood pressure (BP) monitoring are increasingly available in British accident and emergency departments. Our department recently acquired two machines with this capability for use in the resuscitation room. This provided us with an opportunity to compare the speed and frequency of automatic BP recording with the previously used manual method. We found no significant difference in either the median time to the first recording of BP or in the median number of documented recordings in the first hour. However, the overall frequency of BP recording did show a statistically significant increase. We conclude that automation alone does not improve standard practice in this area greatly. PMID- 8452613 TI - An evaluation of a logbook for trainees in accident & emergency medicine in the United Kingdom: senior consultant opinion. AB - A previous paper from the Merseyside Group of Senior Registrars in Accident & Emergency Medicine examined the desirability of a logbook for Higher Specialist Training (HST) in accident & emergency medicine in the United Kingdom and its principal ingredients (Luke et al., 1991). A survey of 100 senior registrars and recently appointed consultants in the specialty identified the main issues of importance to the majority of respondents e.g. certification in advanced cardiac and trauma life support, a minimum of three years in the specialty before appointment as senior registrar and certain key secondments. In this paper, more senior consultants in the specialty were surveyed and a resounding majority concurred with the preferences of their junior colleagues. The findings are discussed and the implications for a future curriculum for postgraduate training in A&E medicine are explored. PMID- 8452614 TI - Characteristics of emergency department utilization in the U.S.A. and the U.K.: a comparison of two teaching hospitals. PMID- 8452615 TI - The S Quattro: a new system for the management of difficult intra-articular fractures of the phalanges. PMID- 8452616 TI - Do ambulance crews triage patients. PMID- 8452617 TI - Should wearing of cycle helmets become compulsory? PMID- 8452618 TI - The cost of treatment of deliberate self-harm. AB - The recent changes in NHS management structure have allowed us for the first time, to estimate the cost of treatment of an illness. We wanted to determine the treatment cost of a case of deliberate self-harm (DSH) to a large University Teaching Hospital and to this aim, we reviewed the case notes of 190 consecutive cases of deliberate self-harm presenting to A&E. On average, each attendance costs 425.24 pounds, from attendance to A&E to hospital discharge. PMID- 8452619 TI - Vasculitic ulcers: a complication of collagen-vascular disorders. PMID- 8452620 TI - Gastrostomy, replacement, feeding tubes: the long and short of it.... PMID- 8452621 TI - A review of calcium alginates. PMID- 8452622 TI - Case study: a hydrogel for infected herpes zoster lesions. PMID- 8452623 TI - Interstitial cystitis. PMID- 8452624 TI - A wound care nurse in dialysis: why the scope of wound physiology is needed in the dialytic setting. PMID- 8452625 TI - Malignancy in transplanted organs. PMID- 8452626 TI - The use of perioperative Doppler ultrasound as a screening test for acute tubular necrosis. AB - For many years Doppler ultrasound has helped to identify the cause of renal allograft dysfunction. However, Doppler examinations were often performed after the onset of acute renal failure. In the present study we used Doppler ultrasound during grafting to follow changes in renovascular resistance. As early as 30 min after the renal artery had been unclamped, the calculated resistance index (RI) at the hilar part of the renal artery was significantly higher in the group of patients who developed acute tubular necrosis (ATN) than in the group of patients with early normalization of renal function (P = 0.05). This result did not correlate with raised cold and warm ischemia times and serum creatinine level on discharge in patients who presented with ATN. RI higher than 0.730 min after unclamping allows for an identification of those grafts at greater risk for the development of ATN and should be an indication for the early introduction of intensive therapy. PMID- 8452627 TI - Effects of donor pretreatment with antilymphocyte serum and cyclosporin on rejection and graft-versus-host disease after small bowel transplantation in immunosuppressed and nonimmunosuppressed rats. AB - After fully allogeneic small bowel transplantation, both graft-versus-host disease (GVHD) and rejection may occur. Donor pretreatment may prevent GVHD, but this sometimes leads to accelerated graft rejection. To study a possible balance between GVHD and rejection, fully allogeneic total orthotopic small bowel transplantation was performed in rats using the WAG-to-BN donor-host combination. Untreated control grafts were rejected in 16.6 +/- 2.7 days (mean +/- SEM), and 35% of the animals had mild, transient GVHD. Pretreatment of the donor with antilymphocyte serum on days -2 and -1 before grafting, with antilymphocyte serum on days -2 and -1 before grafting, with antilymphocyte serum on days -2 and -1 before grafting, either intravenously or intraperitoneally, completely eliminated the occurrence of clinical GVHD but led to significantly shortened survival times (12.3 +/- 0.8 and 10.3 +/- 0.9 days, respectively). Donor pretreatment with 50 mg/kg cyclosporin (CyA) on days -2 and -1 prolonged graft survival significantly to 22.1 days but had no significant effect on the incidence of GVHD. Administration of 25 mg/kg CyA on days 0, 1, 2, 4, and 6 after grafting prolonged survival to 38.3 days with no evidence of GVHD. Pretreatment of the donor with antilymphocyte serum (ALS), combined with the same postoperative, short-term CyA regimen, increased survival to more than 50 days, again with no evidence of GVHD. When CyA was used as both donor pretreatment and postoperative therapy, there was no survival advantage compared to the use of postoperative CyA alone. These results show that an in vivo balance between GVHD and rejection exists and that abrogation of GVHD leads to accelerated rejection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452628 TI - Pontine myelinolysis following liver transplantation: a report of two cases. AB - Two cases of central pontine myelinolysis (CPM) following orthotopic liver transplantation (OLT) are reported. Several months after the onset of this neurological syndrome, the two patients are still alive but with severe neurological sequelae. Some patients undergoing emergency OLT present a high risk of CPM because of pre-existing malnutrition, encephalopathy, and hepatic insufficiency. All of these are associated with an inevitable abrupt rise in sodium serum concentration due to intraoperative compensation of blood losses with high-sodium content blood products. Whenever the renal capacity to excrete sodium is impaired by the surgical procedure, continuous intraoperative venovenous hemofiltration is recommended. PMID- 8452630 TI - Older donors and kidney transplantation. AB - Reluctance to use kidneys from older donors (> 50 years of age) is based on reports of inferior results. We reviewed our experience with 45 kidneys transplanted from older donors. Primary nonfunction, immediate graft function, and 1-, 2- and 3-year graft survival rates were similar to those obtained with kidneys transplanted from donors aged between 20 and 40 years. Renal function at 1 year (as measured by serum creatinine) was poorer in kidneys from older donors. No beneficial effect with respect to graft survival was noted with cyclosporin therapy compared to conventional immunosuppression; however, the numbers are small. We conclude that kidneys from older donors are a valuable source for transplantation. PMID- 8452629 TI - In vitro removal of anti-HLA IgG antibodies from highly sensitized transplant recipients by immunoadsorption with protein A and protein G sepharose columns: a comparison. AB - In the present study we compared the capabilities of sepharose-bound protein A versus protein G columns to remove in vitro lymphocytotoxic anti-HLA antibodies from sera of four highly sensitized renal transplant recipients (PRA > or = 70%). In none of the patients were protein A sepharose columns capable of completely removing anti-HLA antibodies, as demonstrated by the presence of residual alloreactive lymphocytotoxic activity in IgG3 antibodies containing fractions eluted at pH 7. In contrast, no residual anti-HLA lymphocytotoxic antibody activity was found in fractions eluted at pH 7 from protein G columns. These data demonstrate that: (1) IgG 3 antibodies can be partly responsible for lymphocytotoxic anti-HLA reactivity in some sensitized renal transplant recipients and (2) at least in this patient category, in vitro immunoadsorption with protein G is more efficient than protein A sepharose columns in completely removing anti-HLA IgG antibodies from sera. PMID- 8452631 TI - Prediction of hepatic graft viability before reperfusion: an analysis of effluent from porcine allografts. AB - Rapid and reliable assessment of hepatic graft viability is important for successful orthotopic liver transplantation (OLTx). OLTx was performed in 11 pairs of pigs via a venovenous bypass. Six of these grafts were transplanted immediately (group A), while the other five were preserved in University of Wisconsin (UW) solution for 24 h and then transplanted (group B). All grafts were flushed with 300 ml of chilled (4 degrees C) Ringer's lactate solution before reperfusion of the graft, when 20 ml of effluent from the graft was collected and the concentrations of ammonia, lactic acid, GOT, and LDH were measured. Four of the six pigs in group A survived longer than 3 days, while the other two pigs died of causes other than graft dysfunction. All five pigs in group B died either of hemoperitoneum or hemodynamic instability due to liver failure. The histology of postperfusion biopsies in group A showed minimal pathological changes, while the grafts in group B revealed moderate to severe ischemic injuries. Ammonia and lactic acid in the effluent of group B were significantly higher than those of group A (1511 +/- 216 vs 417 +/- 333 micrograms/dl and 114.1 +/- 12.2 vs 91.4 +/- 12.2 mg/dl, respectively; P < 0.05 in both cases). Before reperfusion, the rate of total adenine nucleotides in all of the substances in the graft, which were measured using high performance liquid chromatography (HPLC), inversely correlated with the ammonia levels in the effluent. We conclude that an analysis of the effluent, (i.e. the levels of ammonia and lactic acid), flushed from a hepatic graft before reperfusion could serve as a predictor of hepatic graft viability. PMID- 8452632 TI - Gastrointestinal complications in renal transplantation. AB - One wonders whether the use of cyclosporin, histamine receptor antagonists, low doses of steroids, and early diagnosis and treatment actually modify the incidence, morbidity, and mortality of gastrointestinal (GI) and pancreatic complications in renal transplantation. To find out, we reviewed 614 kidney transplant recipients between January 1984 and December 1988. One hundred patients (16.2%) were found to have GI and/or pancreatic complications in the following distribution: 9.6% gastroduodenal, 1.3% pancreatic, 4% colonic, and 0.4% small bowel. None of the patients presenting a gastroduodenal ulcer had perforation or bleeding. Fifty-five percent of the patients with this complication had a past history of eso-gastroduodenal disease, compared to 19.6% in recipients without gastroduodenal complications. Some 4.4% of the patients had a small bowel or a colonic complication and four died of peritonitis due to bowel perforation. Mortality was 35% in those having intestinal resection and/or perforation with peritonitis. Sixteen percent of patients with colonic complications had a known history of diverticula, compared to 3% for those without colonic complications. The incidence of GI and/or pancreatic complications in renal transplant recipients remains high and has caused 1.1% of the deaths in our series. Mortality is essentially due to upper GI bleeding, peritonitis following perforation, and infectious colitis. Better detection of gastroduodenal and colonic disease before transplantation seems to be mandatory. Prevention with histamine H2 receptor antagonists and early surgical treatment of complicated colonic diverticula help to reduce the morbidity and mortality in kidney graft recipients. PMID- 8452633 TI - Misdiagnosed malignancy in transplanted organs. AB - The case reports of three patients who received cancer-bearing organs at this institution are presented. A fourth recipient, who was to be transplanted with a cancerous kidney, was spared this disastrous complication. The relevant data regarding the donors is also alluded to, with special reference to the type and site of the primary malignancy. Following these case reports, the implications of these issues, their possible prevention, and further management are discussed. PMID- 8452634 TI - Visceral leishmaniasis after orthotopic liver transplantation: impact of persistent splenomegaly. AB - Visceral leishmaniasis was observed in a 50-year-old female liver transplant recipient 1 year following transplantation. Signs of active infection were low grade fever, pancytopenia, persistent splenomegaly, positive cultures for leishmania in liver and bone marrow biopsy specimens, and newly positive leishmania serology. Following sequential therapy with pentavalent antimony and amphotericin B, blood values improved massively, bone marrow cultures became negative, and leishmania serology decreased. Secondary prophylaxis with fluconazole was instituted and the patient remains without signs of active infection 1 year after successful therapy. PMID- 8452635 TI - HLA-DR typing of organ donors and allograft recipients by SSO typing: correlation with serotyping in the North Italy Transplant Program. PMID- 8452636 TI - An in vitro method for comparing the efficacy of two preservation solutions in one canine liver using the 5'-nucleotidase assay. AB - The activity and localization of the plasma membrane-bound enzyme 5'-nucleotidase (5'-NT) in liver tissue are sensitive parameters of ischemic damage. The value of 5'-NT as a marker of liver graft viability was studied in relation to liver preservation. In six mongrel dogs, the main right and left branches of the portal vein were cannulated and flushed separately in situ with cold University of Wisconsin (UW) solution and Euro-Collins (EC) solution, respectively. After hepatectomy, the right and left liver lobes were split and stored at 5 degrees C in either of the two solutions. 5'-NT activity was demonstrated in cryostat sections of liver tissue using the lead salt method. After 48 h of storage in EC solution, the 5'-NT score had decreased to 31% +/- 16% (n = 6), whereas in UW solution the 5'-NT score was 76% +/- 10% (n = 6). Significantly (P < 0.05) higher 5'-NT scores were also found after 24-h and 72-h preservation times in UW versus EC solutions. This result is in keeping with the higher preservation tolerance of liver grafts preserved in UW solution. The 5'-NT assay was studied in relation to graft function in orthotopic liver transplantation experiments in dogs. All dogs with liver grafts preserved in UW solution for 24 h (n = 4) and 48 h (n = 3) survived (> 5 days). Pretransplant 5'-NT scores ranged from 61% to 100%. The 72-h preserved livers (n = 5) did not show life-supporting function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452637 TI - The mouse relaxin gene: nucleotide sequence and expression. AB - Relaxin is a polypeptide hormone that has a variety of physiological effects both on remodelling of collagen and on uterine contractility. These are most apparent during pregnancy. The sequences of relaxin cDNAs derived from ovaries of late pregnant random-bred Swiss mice have been established. Multiple subclones obtained from three independent polymerase chain reaction experiments were found to encode relaxins which were identical except at position 11 in the A chain (Ile or Val). All mouse relaxin cDNAs expressed in the ovary during pregnancy had an extra tyrosine inserted prior to the final A chain cysteine residue, a result confirmed by direct sequencing of relaxin peptides. Whilst this tyrosine insertion must have local effects on the folding of the A chain, structure activity studies will clarify whether it perturbs functional interaction with the relaxin receptor. We have shown that there is a single relaxin gene in the mouse genome, and that expression during pregnancy occurs in the ovary but is not detectable in the placenta, uterus or fetus. PMID- 8452638 TI - Post-transcriptional regulation of bovine parathyroid hormone synthesis. AB - Incubation of bovine parathyroid cells for 48 h in 0.4 mmol calcium/l had no significant effect on steady-state preproparathyroid hormone (preproPTH) mRNA levels when compared with cells incubated in 1.0 mmol calcium/l, but low calcium concentrations increased the membrane-bound polysomal content of preproPTH mRNA by 200 +/- 16% (mean +/- S.D.). No preproPTH mRNA was detected on free polysomes. Actinomycin D (5 and 10 micrograms/ml) had no effect on steady-state preproPTH mRNA levels measured in dot-blot assays after 24 h, but reduced levels in cells incubated in 1.0 mmol calcium/l to 54 +/- 16% and 39 +/- 12% of control values respectively after 48 h of incubation. Similarly, in cells incubated in 0.4 mmol calcium/l, actinomycin D (5 and 10 micrograms/ml) reduced steady-state preproPTH mRNA levels to 57 +/- 13% and 45 +/- 5% of control values respectively. Actinomycin D did not prevent the rise in polysomal content of preproPTH mRNA induced in cells by incubation in 0.4 mmol calcium/l, but increased polysomal content in cells incubated in 0.4 and 1.0 mmol calcium/l by 159 +/- 9% and 164 +/ 13% respectively after 48 h. These results demonstrate post-transcriptional regulation of PTH synthesis in cultured bovine parathyroid cells, and suggest that this control involves a protein which may be calcium-sensitive. PMID- 8452639 TI - Regulation of arginine vasopressin mRNA in rat fetal hypothalamic cell culture. Role of protein kinases and glucocorticoids. AB - Studies have been performed to investigate the regulation of arginine vasopressin (AVP) mRNA expression in fetal hypothalamic cultures. AVP mRNA-positive neurones were identified by in-situ hybridization histochemistry, and changes in mRNA expression were quantitated by nuclease protection assay. Both protein kinase C and protein kinase A activators increased the expression of AVP mRNA, in contrast to dexamethasone, which inhibited the responses to both protein kinase C and protein kinase A activation. PMID- 8452640 TI - Interaction of diazoxide and cromakalim with ATP-regulated K+ channels in rodent and clonal insulin-secreting cells. AB - The hyperglycaemia-inducing sulphonamide diazoxide has been previously shown to mediate its effects upon insulin secretion by opening K+ channels and hyperpolarizing the beta-cell membrane. The target site has been characterized as the ATP-regulated K+ (K+ATP) channel protein. In the present study, a detailed investigation of interactions of diazoxide and another K+ channel opener, cromakalim, with K+ATP channels has been performed in individual insulin secreting cells using patch-clamp techniques. In agreement with previous studies, diazoxide and cromakalim were found to be effective only when ATP was present upon the inside face of the plasma membrane. The ability of both diazoxide and cromakalim to open channels was, however, found to diminish with time following isolation of inside-out patches. Within seconds of forming the recording configuration, the actions of both compounds were potent, and were found to decline steadily as the number of operational channels decreased ('run-down'). In open cells, where the plasma membrane remains partially intact, the rate of run down was significantly reduced, and effects of channel openers were recorded up to 80 min following cell permeabilization. We also demonstrated that in the absence of ATP, but in the presence of ADP, both diazoxide and cromakalim were able to open K+ATP channels. Interestingly, once the effects of diazoxide and cromakalim on K+ATP channels in the presence of ATP were lost, both compounds opened channels in the presence of ADP. One implication of these data is that the actions of diazoxide and cromakalim involve regulatory proteins associated with the ion channel; this molecule is able to bind ATP, ADP and possibly other cytosolic nucleotides. PMID- 8452641 TI - Localization of progesterone-associated endometrial protein mRNA by in-situ hybridization in human pregnancy decidua, endometriosis and borderline endometrioid adenoma. AB - Progesterone-associated endometrial protein (PAEP) has been isolated from human decidualized endometrium. In-situ hybridization histochemistry was employed to determine the cellular localization of PAEP mRNA in decidua during pregnancy. PAEP mRNA was found to be expressed in the glandular epithelium of decidua spongiosa throughout pregnancy. Substantial variations in the amount of PAEP mRNA during the course of pregnancy were observed, and it was most abundant at the end of the first trimester. We also found that the PAEP gene was expressed in endometriosis and in a borderline endometrioid adenoma. As in decidual tissues, PAEP mRNA in endometriosis was abundant in the glandular compartment. PMID- 8452642 TI - Developmental expression of the relaxin gene in the porcine corpus luteum. AB - Northern analysis and in-situ hybridization were used to follow the development of relaxin gene expression in the newly forming corpus luteum (CL) after ovulation and throughout luteal development. Alkaline phosphatase (AP) was used as a marker of theca-derived lutein cells and the relationship between AP positive and relaxin mRNA-containing cells was assessed. Ovaries from prepubertal pigs treated with pregnant mares serum gonadotrophin (PMSG)/human chorionic gonadotrophin (hCG) were collected during the periovulatory period and at various times during 19 days after ovulation. In addition, CL from cyclic pigs on days 10 and 16 were used to monitor relaxin gene expression in small and large luteal cells. Northern analysis revealed that relaxin gene expression increased with CL development in the PMSG/hCG-treated pig, reaching maximal levels at around day 14 post-ovulation. Thereafter, as the CL regressed, the level of relaxin mRNA declined. In CL from cyclic pigs at day 10 of the cycle, only small luteal cells expressed relaxin mRNA. However, by day 16 of the cycle, large luteal cells were the source of relaxin gene expression. In-situ hybridization studies revealed that in the early CL (up to 30 h post-ovulation), the relaxin gene transcript was observed in cells along the margins of the CL and in the core of the infolding follicle wall corresponding to the AP-positive, luteinized theca cell layer. As luteinization progressed, the theca and granulosa cell layers could no longer be distinguished morphologically (from 54 h after ovulation until day 9). However, the pattern of relaxin hybridization persisted along the periphery in bands of cells penetrating the CL, and coincided with areas of AP staining, indicating that the theca lutein cells were the site of relaxin gene expression. At day 14, relaxin hybridization and AP staining were distributed throughout the luteal tissue. With CL regression both AP staining and relaxin hybridization declined. This pattern of relaxin hybridization in the CL of the gonadotrophin-primed pig was identical to that observed in cyclic pigs on days 10 and 16 of the cycle. These findings indicate that theca interna cells retain their ability to express the relaxin gene following ovulation and luteinization. In the early CL, the small theca-derived lutein cells are the source of relaxin transcript. However, as the CL becomes fully differentiated, the large granulosa-derived lutein cells acquire the capacity to express the relaxin message. PMID- 8452643 TI - Insulin-like growth factor-I gene expression is increased in the right ventricular hypertrophy induced by chronic hypoxia in the rat. AB - Rats were maintained in chambers and breathed air (control, n = 8) or an atmosphere containing 10% oxygen (hypoxic, n = 10) for 35 days. On completion of the experiment the hypoxic animals weighed less than the controls (hypoxic, 290 +/- 11.7g; control, 339 +/- 19.2g; means +/- S.E.M., p < 0.05). No differences in the left ventricular weights were found between groups but the right ventricular weights were greater in the hypoxic rats (hypoxic, 0.39 +/- 0.02g; control, 0.27 +/- 0.08g; p < 0.01). The amount of mRNA for IGF-I in the ventricles was quantified by Northern blot analysis. There was no difference between groups in IGF-I mRNA levels in the left ventricles (hypoxic, 1.07 +/- 0.41 absorbance units (AU); control, 0.73 +/- 0.33 AU). In the right ventricles, IGF-I mRNA was greater in hypoxic than in control rats (hypoxic, 2.37 +/- 0.75 AU; control, 0.64 +/- 0.11 AU; p < 0.05). This study demonstrates that expression of IGF-I mRNA is increased in the hypertrophied right ventricle of hypoxic rats; IGF-I may play a central role in the initiation and maintenance of this process. PMID- 8452644 TI - Fetal facial defects: associated malformations and chromosomal abnormalities. AB - During an 8-year period, facial defects were observed in 146 (7%) of the 2,086 fetuses that underwent karyotyping in our unit because of fetal malformations and/or growth retardation. Chromosomal abnormalities were detected in 37 of 56 (66%) fetuses with micrognathia, in 10 of 13 (77%) with macroglossia, in 31 of 64 (48%) with cleft lip and palate, in 5 of 11 (45%) with severe hypotelorism or cyclops, and in 6 of 19 (32%) with nasal hypoplasia, proboscis or single nostril. Macroglossia was mainly associated with trisomy 21, micrognathia with trisomy 18 and triploidy, facial cleft with trisomies 13 and 18, and ocular or nasal defects with trisomy 13. In all chromosomally abnormal fetuses with facial defects, there were additional multisystem defects, and the pattern of these malformations was compatible with the type of the underlying chromosomal abnormality. In the total series of 2,086 fetuses with malformations and/or growth retardation, there were 31 with trisomy 13, 83 with trisomy 18 and 69 with trisomy 21; facial defects were found in 71, 36 and 14% of these fetuses, respectively. PMID- 8452645 TI - Abnormal second-trimester ultrasounds: an indication for karyotype. AB - There are limited data on the risks of aneuploidy for normal-appearing fetuses with amniotic fluid volume (AFV) abnormalities. The purpose of this study was to determine the relative risks of aneuploidy associated with second-trimester abnormal AFVs and fetal structural anomalies in a cohort of 2,823 singleton, viable fetuses. Compared to gravidas younger than 35 with normal ultrasounds, normal fetuses had an increased incidence of aneuploidy with polyhydramnios, increased AFV, i.e. subjectively increased but normal by maximum vertical pocket (MVP) and/or amniotic fluid index (AFI), oligohydramnios, and decreased AFV, i.e. subjectively decreased but normal by MVP and/or AFI. These included: increased AFV [odds ratio = 12.9, 95% confidence interval (CI) = 4.1-39.4], polyhydramnios (odds ratio = 4.6, CI = 0.6-36.8), and decreased AFV (odds ratio = 3.8, CI = 1.1 13.1). There were no aneuploidies among the 28 normal fetuses with oligohydramnios. Anomalous fetuses had a markedly increased incidence of aneuploidy (odds ratio = 13.4, CI = 7.2-24.9). We conclude that fetal structural anomalies as well as isolated AFV abnormalities were associated with an increased risk for aneuploidy. PMID- 8452646 TI - Prenatal diagnosis of cystic fibrosis: ultrasonography of the gallbladder at 17 19 weeks of gestation. AB - We have investigated the ultrasonographic signs that can help in the prenatal diagnosis of cystic fibrosis in 197 risk fetuses and compared them with 353 control fetuses. In 60 fetuses with a 1:4 risk for the disease, the gallbladder was also examined. All ultrasonograms were performed just before amniocentesis at 17-19 weeks of gestation. A previously described intra-abdominal hyperechogenic mass was found in 73% of the 48 affected fetuses, but 32 of the 149 unaffected fetuses also had this feature, giving a specificity of 77% and a sensitivity of 78%. When we investigated the gallbladder, we found 9 of the 12 affected fetuses to be without evidence of a gallbladder during the sonographic examination (none of the healthy or control fetuses had such a feature), giving a positive predictive value of 100%, a specificity of 100% and a sensitivity of 75%. The combined presence of an abnormal gallbladder and a hyperechogenic intra-abdominal mass yields the same positive predictive value and specificity, but does not improve the accuracy. Ultrasonography appears to be a good additional diagnostic tool for the prenatal diagnosis of cystic fibrosis, especially when the enzyme activities disagree. Furthermore, these results lead us to think that such a finding during routine ultrasonographic examination at 17-29 weeks could be a means of screening for cystic fibrosis. The absence of the gallbladder during the sonographic examination of fetuses at risk for cystic fibrosis at 17-19 weeks of gestation can help in the prenatal detection of the disease. PMID- 8452647 TI - Hemodynamic changes during cardioversion in utero: a case report of supraventricular tachycardia and atrial flutter. AB - Two cases of fetal tachyarrhythmias were treated in utero. One case showed supraventricular tachycardia which was successfully treated with procainamide. The other case was an atrial flutter with 2:1 atrioventricular conduction (AVC) which was treated with digoxin and verapamil. In both cases, the blood flow in the descending aorta was observed using pulsed Doppler ultrasound during therapy. In the first case, the interval of blood flow peaks was suddenly prolonged to normal heart rate, and in the second case, the blood flow peaks appeared irregularly which indicated that (AVC) was intermittently blocked. The blood flow pattern represented the mode of cardioversion. The blood flow velocity was also measured in both cases; it decreased transiently during therapy representing a depression in cardiac function. The cause of this was thought to be the negative inotropic effects of procainamide and verapamil. In spite of these negative inotropic effects, a greater R-R interval means a greater stroke volume. This relationship has a favorable effect on the fetal circulation as a result of therapy for fetal tachyarrhythmias. PMID- 8452649 TI - Cowper's glands cysts--a cause of transient intra-uterine bladder outflow obstruction? PMID- 8452648 TI - In utero treatment of toxoplasmic fetopathy with the combination pyrimethamine sulfadiazine. AB - The mothers of 52 fetuses with toxoplasma fetopathy diagnosed in utero were treated with a combination pyrimethamine-sulfa drug and spiramycine. Their infants were compared to a group of 51 infants whose mothers had received spiramycine alone. Postnatal treatment was identical in both groups. Parasitological investigation of the placenta was positive in 42 and 76.6%; the newborns had a specific IgM of 17.4 and 69% in groups 1 and 2, respectively. These differences were significant. The mean specific IgG titer was significantly reduced at birth and at 4-6 months of age in group 1. According to the results obtained in the present material the pyrimethamine-sufa drug combination, given to the mothers of fetuses infected with toxoplasma, has a significant effect on the parasitological and serological signs of evolutive fetopathy. It did not significantly alter the clinical pattern, probably because the onset of treatment was too long after maternal infection. PMID- 8452650 TI - Prenatal diagnosis of lissencephaly by magnetic resonance image. AB - Two cases of lissencephaly were prenatally diagnosed by a magnetic resonance image (MRI). Smooth surface of brain and remarkable sylvian fissure, which were barely detectable by ultrasound, were easily observed in MRI. MRI is the most appropriate tool in diagnosing lissencephaly. PMID- 8452651 TI - Fetal thyroid function. AB - Cordocentesis has permitted the study of fetal thyroid function. In normal pregnancy, fetal blood thyroid-stimulating hormone (TSH), thyroid hormones and thyroid-binding globulin increase with advancing gestation demonstrating functional maturation of the pituitary, thyroid and liver, respectively. The administration of thyroid-releasing hormone to the mother produces a rapid increase in fetal TSH from at least 25 weeks gestation. In hypoxemic growth retarded fetuses, the concentrations of TSH are higher, and the concentrations of total and free thyroxine are lower than in appropriately grown fetuses. In anemic fetuses from red cell-isoimmunized pregnancies, serum TSH and thyroid hormone concentrations are increased. In some chromosomally abnormal fetuses, particularly those with trisomy 21, TSH is increased. PMID- 8452652 TI - Human antibodies to HIV-1 by recombinant DNA methods. PMID- 8452653 TI - B cell antigenic site mapping of HIV-1 glycoproteins. PMID- 8452654 TI - Antigenic and immunogenic sites of HIV-2 glycoproteins. PMID- 8452655 TI - Coumarin-induced skin necrosis. Incidence, mechanisms, management and avoidance. AB - Coumarin-induced tissue necrosis is a complication of oral anticoagulant therapy characterised by necrosis of the skin and underlying tissue. This occurrence of microvascular thrombosis associated with the administration of an anticoagulant has perplexed the medical and pharmaceutical community since the condition was first recognised in 1943. While the condition is rarely seen, it is of major clinical interest and raises a number of questions concerning pathological mechanisms and patient management. Although some cases occur in patients with hereditary disorders predisposing to thrombosis, the condition remains a mystery in terms of which patients will develop the condition, why the skin and underlying fatty tissues are the target of the microvascular thrombosis, and what the proper approach to a patient with coumarin-induced necrosis should be both in terms of acute management and long term anticoagulant therapy. PMID- 8452656 TI - Stereoisomers and drug toxicity. The value of single stereoisomer therapy. AB - All drugs produce adverse effects, though the risk varies widely between different compounds. Many toxic reactions are an extension of the mechanism responsible for the therapeutic effect and can be avoided by careful dose adjustment. Other adverse events are not related to the beneficial action of the drug. Recent interest has focused on the role of the different properties of individual drug enantiomers in causing drug toxicity. For drugs with a single chiral centre, both enantiomers may be therapeutically active. However, if the main therapeutic benefit is in only 1 enantiomer, several possibilities exist for the other enantiomer--inactive, a qualitatively different effect, an antagonistic effect or greater toxicity. PMID- 8452657 TI - How frequent are notified severe cutaneous adverse reactions to Fansidar? AB - An attempt was made to estimate the risk of severe cutaneous adverse reactions (SCARs) to Fansidar (sulfadoxine plus pyrimethamine). Cases were identified through a spontaneous reporting system. Persons exposed were estimated using sales data of 27 countries reporting one SCAR case for either Fansidar or a related product, Bactrim (cotrimoxazole; sulfamethoxazole plus trimethoprim). Between 1974 and 1989, 126 cases were notified for Fansidar: 87 cases of erythema multiforme or Stevens-Johnson syndrome, and 39 cases of toxic epidermic necrolysis. 86% of cases were reported in Europe or North America. In 116 cases with use known, prophylaxis was the reason in 103, and treatment in 13. Toxic epidermolysis and erythema multiforme/Stevens-Johnson syndrome had case fatalities of 36 (95% confidence intervals 21 to 53%) and 9% (4 to 18%), respectively. Fansidar users were estimated at 117 million, and the overall SCAR risk to be 1.1 (0.9 to 1.3) per million. For developing countries with mainly single dose use, the risk was estimated to 0.1 (0.0 to 0.1) per million. For Europe and North America with mainly prophylactic use, the risk was 10 (8 to 12) and 36 (23 to 48) per million, respectively. Prophylactic use had a 40 times higher risk than single dose therapeutic use. The aggregated risk peaked in 1984 1985, with global and North American SCAR frequencies of 3.4 (2.4 to 4.3) and 72 (41 to 102) per million, respectively. After 1985, North America reported only one further case despite continued use by an estimated 0.3 million persons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452658 TI - Fatal fulminant autoimmune haemolytic anaemia associated with tolmetin use and gastric carcinoma. Case report and literature review. AB - Presented is a case report of an 80-year-old man with dyspnoea and jaundice who died from autoimmune haemolytic anaemia (AIHA) within 12 hours of arrival at the emergency department. The patient had been taking tolmetin for osteoarthritis. On autopsy he was found to have a superficial gastric adenocarcinoma. A brief presentation on AIHA includes primary (idiopathic) and secondary types. Factors associated with AIHA include nonsteroidal anti-inflammatory drugs (NSAIDs) and gastric carcinoma, although a direct cause cannot be demonstrated. After a discussion of the autoimmune mechanism of drug-associated hemolysis of which methyldopa is the prototype, a review of NSAIDs associated with AIHA is presented. All (18) NSAID cases of immune haemolysis were reviewed to determine which were more likely due to an autoimmune mechanism. These included 3 cases with tolmetin use: one probable and one possibly having an autoimmune basis for haemolysis, while with the third case immune haemolysis was by the drug adsorption mechanism. A review of gastric carcinoma associated with AIHA reveals only 2 previously reported cases. The associations of tolmetin use, as well as gastric carcinoma with AIHA, both rare, are noteworthy but cannot be proven as causative factors with our current level of knowledge and technology. PMID- 8452659 TI - Tryptophan. Current status and future trends for oral administration. PMID- 8452662 TI - Adverse haematological complications of anticancer drugs. Clinical presentation, management and avoidance. AB - Haematological complications frequently occur in patients treated with chemotherapeutic agents. The degree and duration of bone marrow suppression depends upon the type of agent used. In general, agents that are cell cycle phase specific tend to cause early myelosuppression with rapid marrow recovery, as compared to the non-phase-specific agents. Host factors including patient age, nutritional status, marrow infiltration or damage, and hepatic and renal function also affect haemotoxicity. Chemotherapeutic agents suppress proliferating or potentially proliferating precursors of neutrophils, platelets and red blood cells to the same extent. With most drugs, neutropenia tends to be dose limiting and more severe than thrombocytopenia. Because of the longer life span of red blood cells, severe anaemia is rarely a problem. The management of myelosuppression is multifaceted, and consists of aggressive antibiotic therapy to treat or prevent the infections that occur with neutropenia, as well as red blood cell and platelet transfusion support to correct anaemia and prevent bleeding. The role of the haemopoietic growth factors including erythropoietin, colony-stimulating factors and the interleukins is currently being evaluated in clinical trials. Haemolytic uraemic syndrome, haemolytic anaemia and therapy induced myelodysplasia and/or acute leukaemia are uncommon and potentially severe complications of chemotherapeutic agents. PMID- 8452661 TI - Antidepressant drugs and the emergence of suicidal tendencies. AB - Although antidepressant medications represent the cornerstone of treatment for patients with moderate to severe clinical depression, they also carry serious risks. There is evidence which suggests that antidepressants can, in rare instances, induce or exacerbate suicidal tendencies. Nine clinical mechanisms have been proposed through which this may occur. These are: (a) energizing depressed patients to act on pre-existing suicidal ideation; (b) paradoxically worsening depression; (c) inducing akathisia with associated self-destructive or aggressive impulses; (d) inducing panic attacks; (e) switching patients into manic or mixed states; (f) producing severe insomnia or interfering with sleep architecture; (g) inducing an organic obsessional state; (h) producing an organic personality disorder with borderline features; and (i) exacerbating or inducing electroencephalogram (EEG) or other neurological disturbances. Epidemiological and controlled studies also provide data on the association between antidepressant drugs and suicidal ideation, attempts and fatalities. These include studies which: (a) suggest that electroconvulsive therapy may be more effective than antidepressant drugs in reducing the frequency of suicide attempts; (b) indicate that antidepressants may differ in their capacity to reduce the frequency of suicide attempts; (c) find that more overdose attempts were made by patients receiving maprotiline than placebo; and (d) suggest that fluoxetine may be associated with a greater risk of inducing de novo suicidal ideation. Evidence suggests that antidepressants may vary by at least 15-fold in the number of fatal overdoses per million prescriptions. Estimated overdose proclivity rates were derived after adjusting the fatal toxicity data by the therapeutic index of the drug. These rates were very consistent between agents with the same pharmacological properties, and correlated well with known overdose risk rates for amitriptyline, mianserin and maprotiline. Estimated overdose proclivity rates suggest that the highly selective noradrenaline (norepinephrine) uptake inhibitors (desipramine, nortriptyline, maprotiline) may be associated with a greater risk for overdose than more mixed uptake inhibitors and monoamine oxidase inhibitors (MAOIs). Antidepressants are not uniformly neutral in regard to suicidal ideation and attempts. Data clearly demonstrate that antidepressants ameliorate suicidal ideation more effectively than placebo in patients with depression. Although antidepressants diminish suicidal ideation in many recipients, about as many patients experience worsening suicidal ideation on active medication as they do on placebo. Furthermore, at least as many patients attempted suicide on fluoxetine and tricyclic antidepressants as on placebo, and more patients attempted to overdose on maprotiline than placebo. These observations suggest that antidepressants may redistribute suicide risk, attenuating risk in some patients who respond well, while possible enhancing risk in others who respond more poorly.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8452663 TI - Sexual function in women. Do antihypertensive drugs have an impact? AB - Drug-induced sexual dysfunction is well known to occur with antihypertensive drugs in men. There are much less data on the effects of drugs on female sexual function. The physiology of the female sexual response has similarities to that of the male sexual response and there are therefore good reasons for suspecting that antihypertensive drugs are likely to adversely affect sexual function in women. Present evidence suggests that clonidine, methyldopa, guanethidine and reserpine are associated with adverse effects on sexual function. In healthy volunteers, labetalol appears to reduce vaginal lubrication, but there are no studies in patients receiving the drug therapeutically. Thiazide diuretics may be associated with the worsening of sexual problems, which interestingly appear to be ameliorated by weight reduction. Present evidence on the effects of vasodilators is limited but the evidence suggests that sexual function in women receiving calcium antagonists is not altered by changing to an angiotensin converting enzyme (ACE) inhibitor. Although present evidence suggests that effects on female sexual function may not be very great, it should be recognised that there are very few data in this area. Further work is clearly necessary. PMID- 8452660 TI - Adverse drug interactions with nonsteroidal anti-inflammatory drugs (NSAIDs). Recognition, management and avoidance. AB - The prevalence and incidence of adverse drug interactions involving nonsteroidal anti-inflammatory drugs (NSAIDs) remains unknown. To identify those proposed drug interactions of greatest clinical significance, it is appropriate to focus on interactions between commonly used and/or commonly coprescribed drugs, interactions for which there are numerous well documented case reports in reputable journals, interactions validated by well designed in vivo human studies and those affecting high-risk drugs and/or high-risk patients. While most interactions between NSAIDs and other drugs are pharmacokinetic, NSAID-related pharmacodynamic interactions may be considerably more important in the clinical context, and prescriber ignorance is likely to be a major determinant of many adverse drug interactions. Prescribing NSAIDs is relatively contraindicated for patients on oral anticoagulants due to the risk of haemorrhage, and for patients taking high-dose methotrexate due to the dangers of bone marrow toxicity, renal failure and hepatic dysfunction. Combination NSAID therapy cannot be justified as toxicity may be increased without any improvement in efficacy. Where lithium or anti-hypertensives are coprescribed with NSAIDs, close monitoring is mandatory for lithium toxicity and hypertension, respectively, and aspirin (acetylsalicylic acid) or sulindac are preferred. Phenytoin or oral hypoglycaemic agents may be administered with NSAIDs other than pyrazoles and salicylates provided that patients are monitored carefully at the initiation and cessation of NSAID treatment. Digoxin, aminoglycosides and probenecid may be coprescribed with NSAIDs, but close monitoring is required, particularly for high-risk patients such as the elderly. Indomethacin and triamterene should be avoided due to the risk of renal failure. High dose aspirin should be replaced by naproxen in patients on valproic acid (sodium valproate) and care is required when corticosteroids are administered to patients taking salicylates long term in high dosage. Interactions between NSAIDs and antacids or cholestyramine are generally avoidable. Adverse drug interactions involving NSAIDs may be limited by rational prescribing and by careful monitoring, particularly for high-risk patients, drugs and therapy periods. PMID- 8452665 TI - The way towards adverse event monitoring in clinical trials. AB - Different approaches to the monitoring of adverse reactions to drugs have been used over the years, with the aim of preventing catastrophes like the thalidomide episode and to rationalise drug usage. In the 1960s, the use of national and international adverse event monitoring was first suggested by the British statistician, David Finney. According to Finney, the method was well suited for the postmarketing surveillance of drugs. The idea was rejected by the World Health Organization (WHO) but was later taken up by the Prescription Event Monitoring Event System in the UK. Subsequent to problems with practolol in the 1970s it was suggested that adverse event monitoring could also be useful in clinical trials to detect adverse reactions before a drug is launched. The idea of adverse event monitoring has been tested by Astra Hassle in Sweden in clinical trials with felodipine and omeprazole, and is now the standard method within the company. Adverse event monitoring is an expensive and time-consuming method seen from a short term perspective. However, such monitoring offers an opportunity to optimise the use of clinical trials in safety monitoring, and its ability to predict possible adverse drug reactions is superior to other methods. PMID- 8452666 TI - Bactericidal/permeability increasing protein and host defense against gram negative bacteria and endotoxin. AB - The bactericidal/permeability increasing protein is a major element in the host defense against Gram-negative bacteria and endotoxin, acting intracellularly in the polymorphonuclear leukocyte. As an isolated protein, bactericidal/permeability increasing protein also acts as an extracellular bactericidal and endotoxin-neutralizing agent and, when injected, protects animals against lethal effects of Gram-negative bacteria and endotoxin. PMID- 8452664 TI - Immunological adverse effects of anticonvulsants. What is their clinical relevance? AB - Long term administration of anticonvulsants is sometimes associated with impairment of the humoral and/or cellular immune response. Furthermore, certain well known adverse reactions to antiepileptics may have an immunotoxicological origin e.g. lymphadenopathy, pseudolymphoma and systemic lupus erythematosus. However, two important questions remain unresolved. First, the possibility that epilepsy per se might be primarily associated with immune alterations makes it difficult to assess the pathogenetic role of a specific drug, especially in a patient population usually on multiple drug therapy. Secondly, the clinical relevance of some of the observed immunological abnormalities is still highly controversial. This review is intended to give an outline of the present state of knowledge on the effects of anticonvulsants on humoral, cellular and nonspecific immunity, with particular regard to some of the major clinical conditions that have been ascribed to drug-induced immune dysregulation, such as pseudolymphoma and systemic autoimmune diseases. The immunotoxic potential of anticonvulsants appears to be low, and immunological monitoring is not usually required except in patients with known immune defects. PMID- 8452667 TI - Glucocorticoids, lipocortins and the immune response. AB - Glucocorticoids are immunosuppressive and antiinflammatory agents that act through multiple mechanisms. This review highlights recent evidence that lipocortin-1, a member of the annexin family of calcium-binding proteins, can be induced by glucocorticoids, and may mediate some of the effects of glucocorticoids through putative lipocortin-1 receptors, which have been found on the surface of phagocytic cells. Recent advances in annexin biology have been drawn together to formulate a novel hypothesis for the regulation of inflammation. PMID- 8452668 TI - Nuclear signaling by interleukin-6. AB - The molecular analysis of the regulation of nuclear proteins induced by interleukin-6 has provided new insights into this largely unknown signal transduction pathway. Transcription factors of the CCAAT/enhancer-binding protein and AP-1 families, as well as the octamer-binding proteins and the tumor suppressor gene product pRB, are regulated by interleukin-6 in a cell type specific manner, suggesting that they may play a role in the nuclear signaling by interleukin-6. PMID- 8452669 TI - Antigen recognition. PMID- 8452670 TI - Innate immunity. PMID- 8452671 TI - Structure and function of genes in the MHC class II region. AB - Genes required for antigen processing map to the MHC class II region. For the endogenous (class I) antigen processing pathway, many hypotheses concerning the structure and function of the corresponding gene products have been verified during the past year. The identity of the gene(s) involved in the exogenous (class II) pathway remains to be determined. PMID- 8452672 TI - Structure of the HLA class I region and expression of its resident genes. AB - The past year has seen several advances in the analysis of the HLA class I region and some of its resident genes. A description of the human class I gene family and the cloning of the class I region in yeast artificial chromosomes have provided two steps forward in the analysis of the class I region. Advances have been made in understanding the expression of the non-classical HLA class Ib genes and work with the murine class Ib proteins has demonstrated that these antigens can present a specialized subset of peptides to the immune system. PMID- 8452673 TI - Topology and affinity of T-cell receptor mediated recognition of peptide-MHC complexes. AB - Significant progress has been made on several long-standing issues regarding T cell receptor mediated recognition of antigen-MHC complexes. For one, early data suggest that the affinity of the T-cell receptor for the peptide-MHC complex is extremely low, with a KD of approximately 10(-4)-10(-5)M, much weaker than most antibody-antigen interactions. The fact that this affinity is lower than that of some T-cell adhesion molecules for their ligands could have important implications for immune surveillance. A second area of interest is the topology of T-cell receptor recognition; evidence of direct contact between the third complementarity determining region of the T-cell receptor and peptide determinants has been obtained. In addition, the orientation of the T-cell receptor with respect to several antigen-MHC complexes has been predicted. They suggest that whereas most or all peptides seem to bind in the same orientation in both class I and class II MHC molecules, the orientation of the T-cell receptor over the peptide-MHC complex may not be fixed. PMID- 8452674 TI - The basics of binding: mechanisms of antigen recognition and mimicry by antibodies. AB - New insights into the nature of antigen-antibody recognition have been gained through X-ray crystallographic studies of immune complexes. In particular, it has been demonstrated that water molecules form an extended network bridging antigen and antibody, and are essential in achieving shape and chemical complementarity between their interacting surfaces. This finding has important implications for the energetics of the association reaction. Recently, X-ray data on the complex between a peptide hormone and an anti-anti-idiotypic antibody have been obtained. This has relevance to the structural basis of antigen mimicry by antibodies. The conformation of the bound peptide was found to be very similar to that of an antibody complementarity determining region loop, providing a direct structural explanation for how antigen mimicry by anti-idiotypic antibodies might occur. PMID- 8452675 TI - Collectins: pattern recognition molecules involved in first line host defense. AB - A group of chimeric molecules comprising globular heads, which contain the carbohydrate recognition domain, and collagen tails are defined as collectins. The mannose-binding proteins, pulmonary surfactant apoproteins A and D and conglutinin all qualify as members of this family, whose function appears to be as pattern recognition molecules involved in the first line of defense in the pre immune host. PMID- 8452676 TI - Recognition structures on natural killer cells. AB - Recent studies have identified cell surface molecules that appear to play important roles in natural killer cell specificity for their targets. Natural killer cells display activation 'receptors', such as NKR-P1 molecules in rodents, that may activate cytotoxicity by transducing biochemical signals. These molecules presumably interact with target cell surface ligands but these structures have not been elucidated. Natural killer cells display other molecules, such as Ly-49 in mice, that appear to be 'inhibitory' receptors that engage target cell MHC class I molecules and deliver signals, negatively regulating natural killer cell cytotoxic activity. The murine NKR-P1 and Ly-49 molecules are structurally similar and encoded by members of polymorphic gene families that reside in the natural killer gene complex on the distal region of mouse chromosome 6. Additional molecules have been serologically defined and studied functionally in murine and human systems. Thus, the specificity of an individual natural killer cell may be determined by its expressed repertoire of these molecules. The complexities of this recognition system are beginning to be appreciated at the molecular level. PMID- 8452677 TI - The limulus clotting reaction. AB - Our biochemical studies on the hemolymph coagulation-complement system using limulus indicate that the circulating hemocytes contain at least four serine protease zymogens and one clottable protein, coagulogen, which constitute a cascade triggered by bacterial endotoxins and (1,3)-beta-D-glucan. We also found several antimicrobial substances, tachyplesin peptides and anti lipopolysaccharide factor, in the hemocytes. These clotting factors and antimicrobial substances are released into the hemolymph in response to lipopolysaccharide, where they cooperate in immobilization and killing of invading microorganisms as a host defense. PMID- 8452678 TI - Regulation of MHC gene expression. AB - This review focuses on recent progress made in MHC regulation. The better characterization of proteins that interact with MHC class I and II promoters and the isolation of genes encoding several of these transcription factors, such as H 2RIIBP/RXR beta, NK kappa B, I-kappa B, hXBP-1 and NF-Y, allow the functional analysis of these molecules in MHC gene regulation. The application of new techniques, such as genomic in vivo footprinting analysis, to the study of these promoters provides insights into the status of in vivo protein-DNA interaction over these promoters. New insights have also been gained in the understanding of MHC-associated genes. PMID- 8452679 TI - Complement defense mechanisms. AB - The susceptibility of complement-deficient individuals to various severe infections, and studies of the effector mechanisms involved in the destruction of infectious agents, demonstrate the importance of complement in providing an effective host defense system. It is also becoming increasingly apparent that complement not only plays a role in 'natural' defenses against infection and in enhancing the antibody-mediated effector mechanisms, but also influences adaptive immune responses directly. PMID- 8452680 TI - Proteases and lymphocyte cytotoxic killing mechanisms. AB - A subfamily of serine proteases is uniquely expressed by cytotoxic natural killer lymphocytes and T cells. Protease cleavage of different natural substrates is now implicated in the cytotoxic mechanisms of target cell membrane pore formation, DNA fragmentation and cytostasis. PMID- 8452681 TI - Antibiotic peptides and serine protease homologs in human polymorphonuclear leukocytes: defensins and azurocidin. AB - The azurophil granule, a specialized lysosome of neutrophils, contains two families of antimicrobial proteins, each with four members. They are the defensins, comprising human neutrophil protein 1, -2, -3 and -4, on the one hand and the serprocidins, comprising cathepsin G, elastase, proteinase 3 and azurocidin, on the other. Defensins appear to contribute to mammalian as well as invertebrate immunity. Recent studies show that defensins and structurally related peptides are found not only in phagocytes but also in intestinal and respiratory cells. Aside from their antibiotic function, members of the defensin family may also act as hormonal agents. Within the serprocidin family the genes encoding the novel antibiotics and serine protease homologs azurocidin and proteinase 3 have been identified recently. PMID- 8452682 TI - Structure of 6-(3,3-dimethyl-2-oxo-2,3-dihydro-5-furanyl)-2-pyridone at 145 K. AB - C11H11NO3, M(r) = 205.21, triclinic, P1, a = 5.725 (1), b = 9.038 (1), c = 10.401 (2) A, alpha = 101.37 (1), beta = 102.63 (1), gamma = 102.83 (1) degrees, V = 494.7 (3) A3, Z = 2, Dx = 1.38 g cm-3, lambda (Mo K alpha) = 1.7107 A, mu = 0.62 cm-1, F(000) = 216, T = 145 K, R = 0.049, wR = 0.063 for 2386 unique observed reflections. The molecules, which are self-associating in solution, are arranged in the crystal in centrosymmetric dimers joined by N--H...O bonds between the amide functional groups. Analysis of displacement parameters indicates that the furanyl and pyridone groups are independently quite rigid, with the furanyl group librating with respect to the hydrogen-bonded pyridone. PMID- 8452683 TI - Structure of dibenzofuran-d8, C12D8O, at 173 K. AB - Crystalline dibenzofuran-d8 has been found to exhibit disorder of the type described previously for dibenzofuran. The disordered molecules are related to the ordered molecules by a 180 degrees rotation about an axis passing through the molecular center of mass and perpendicular to the furan ring. In the present structure 11(2)% of the molecules were found to adopt this alternate orientation. The molecules are bisected by a mirror plane normal to the furan ring and containing the O atom. The average bond length in the benzenoid ring is 1.392 (10) A. The furan ring and the benzenoid ring are separately planar, but form a dihedral angle of 1.45 (9) degrees with each other. PMID- 8452684 TI - Effects of dizocilpine (MK-801) on rat midbrain dopamine cell activity: differential actions on firing pattern related to anatomical localization. AB - The effects of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine ((+)-MK-801) on the firing pattern of midbrain dopamine neurons were studied with single cell recording techniques in male albino rats anaesthetized with chloral hydrate. The extracellularly recorded electrical activity of single, identified dopamine neurons was studied with respect to firing rate, burst firing and regularity of firing. MK-801 (0.01-1.0 mg/kg IV) induced different effects in different subgroups of midbrain dopamine neurons. In the substantia nigra, firing rate was increased while the pattern was regularized and burst firing slightly increased. In the ventral tegmental area, firing rate and regularity of firing was also increased while effects on burst firing were bidirectional. Histological inspections revealed that neurons which responded with an increase in burst firing were mainly located in the nucleus paranigralis subdivision of the ventral tegmental area, while cells responding with a decrease were predominantly found in the nucleus parabrachialis pigmentosus subdivision. The effects of MK-801 were similar to previously described effects of phencyclidine, another non-competitive NMDA antagonist. The present effects of MK 801 might shed some light on the mechanisms involved in psychotic symptoms induced by phencyclidine and other non-competitive NMDA antagonists. PMID- 8452685 TI - Isolation of a cDNA encoding the human brain serotonin transporter. AB - A cDNA encoding a serotonin transporter (5-HTT) in the human dorsal raphe nucleus was isolated and sequenced using cross-species amplification of human 5-HTT partial cDNA by the polymerase chain reaction (PCR) and the RACE-PCR procedure, designed for rapid amplification of 3' and 5' cDNA ends. The cDNA contains an open reading frame encoding a hydrophobic polypeptide of 630 amino acids with a calculated molecular weight of approximately 70 kDa. The human 5-HTT is approximately 92% homologous to the rat protein but contains an additional consensus phosphorylation site for cAMP-dependent protein kinase recognition located in the cytoplasmic N-terminal region, while a potential protein kinase C phosphorylation site identified in the rat homolog is not conserved in the human 5-HTT. Hydropathicity analysis revealed twelve membrane spanning segments, a topology proposed for other cloned sodium-dependent transporters. PMID- 8452686 TI - [Bioethics committees]. PMID- 8452687 TI - [Severe craniocerebral injuries with a lucid interval]. AB - Some variables were analyzed in 35 patients with severe cranioencephalic injuries following a lucid interval according to mortality. The variables analyzed were: age of less than 40 years, interval of time accident-admission (TAA), admission operation (TAO), level of consciousness (Glasgow scale), associated extracranial lesions, type of intracranial lesion, and tomodensitometric signs of intracranial hypertension. The only variables demonstrating significant statistical differences (p < 0.05) were the level of consciousness (Glasgow scale < 6 points) and the presence of subdural hematoma. Twelve (70.5%) patients who died had less than 6 on the Glasgow scale and in contrast only 5 (27.7%) of the living. Eleven (64.7%) of the group who died and 4 (22.2%) of the living had subdural hematoma. These data suggest that the level of consciousness and the type of lesion are determining factors of the mortality in this type of patients. Early detection and energic treatment of secondary lesions contribute to prognostic improvement of cranioencephalic injuries. PMID- 8452688 TI - [Paraclinical tests in multiple sclerosis. Clinical correlation and predictive value]. AB - The correlation between clinical signs and symptoms, Evoked Potentials (EP) and Magnetic Resonance Imaging (MRI) in Multiple Sclerosis (MS) is still uncertain. It seems necessary to perform comparative studies with homogeneous groups of patients to avoid the error provoked by the selection of patients and the use in the diagnosis of EP and MRI. The aims of this paper were to calculate the sensitivity of EP and MRI in MS in relation to time of evolution and type of MS, to determine the correlation between clinical data and EP and MRI alterations, and to show the predictive value of the paraclinical tests. We have performed clinical examination, EP and MRI in 47 patients with clinically definite MS, Poser's category 1a, without acute attack. Our results show significant correlation between VEP and visual functional scale (FS) (r = 0.43), brainstem auditory EP (BAEP) and Expanded Disability Status Scale (EDSS) (r = 0.33), BAEP and cerebellar FS (r = 0.36), BAEP and brainstem FS (r = 0.29) and somatosensory EP (SEP) and pyramidal FS (r = 0.4). Also, we found significant correlation among clinical data and MRI abnormalities in cerebellum (p < 0.01), brainstem (p < 0.001), and spinal cord (p < 0.01). The SEP (74%), cerebellar (92%) and spinal (83%) MRI alterations provided the greatest agreement with presumed clinical abnormalities. These data confirm the efficacy of EP and MRI to describe the status of MS and support its utility to evaluate the evolution. PMID- 8452689 TI - [Motor neuropathy with conduction blocks]. AB - A series of 4 patients with pure, chronic and progressive motor neuropathy whose main clinical characteristics were asymmetric and distal weakness of the upper limbs, myokymia and fasciculations is presented. There were no sensory impairment and amyotrophy was observed in only one case. This picture suggested the diagnosis of motor neuron disease (MND). However, neurophysiologic examination demonstrated the presence of multifocal conduction blocks (CB) of the motor axons which were preferentially located in the proximal nerve segments and always at points atypical to nerve compression. The peripheral sensitive conductions and the somatosensory evoked potentials were normal, even through the nerve segments where the CB were located. Since this is a treatable potentially reversible syndrome, this motor neuropathy with CB should be included in the differential diagnosis of MND. PMID- 8452690 TI - [Molecular-genetic aspects of neurodegenerative diseases with amyloid plaques]. PMID- 8452691 TI - [Diagnostic value of magnetic resonance in neurosyphilis]. AB - Syphilis is an ever changing disease with an increasing incidence in the last years. Diagnosis of neurological damage remains on cerebrospinal fluid studies and serologic test in patients with appropriate clinical manifestations. Modern neuroimaging techniques are now available in the diagnostic workup of patients with neurosyphilis. Our experience with such techniques in two patients with meningo-vascular syphilis and general paresis points out to the role of magnetic resonance imaging in disclosing ischemic lesions in these patients, although these lesions were not absolutely specific of the disease. PMID- 8452692 TI - [Spinal cord compression syndrome as the clinically presenting form of a T-cell immunoblastic lymphoma: follow-up with magnetic resonance]. PMID- 8452693 TI - [Arnold-Chiari malformation and paroxysmal symptoms]. PMID- 8452694 TI - [Discoid lupus erythematosus in a patient with Melkersson-Rosenthal syndrome]. PMID- 8452695 TI - [A case of pure anarthria]. PMID- 8452696 TI - [Fine-needle myelography. Current status]. PMID- 8452697 TI - [Idiopathic striato-pallido-dentate calcification]. PMID- 8452698 TI - [Esophageal pseudoachalasia related to a neoplasm]. AB - Differential diagnosis between idiopathic achalasia and esophageal pseudoachalasia is difficult to perform. One hundred and forty-four consecutive patients with a clinical diagnosis of primary esophageal motor disorder have been evaluated for pneumatic dilatation of the cardias. Of them, 6 (4.1%) have been finally diagnosed of esophageal pseudoachalasia with carcinoma of the cardias, although in four cases more than one biopsy procedure was needed to establish the diagnosis. The clinical data--higher age, shorter clinical history and higher weight loss--, the higher pressure of the lower esophageal sphincter and the failure of the dilatation suggested the diagnosis, but were uncertain findings. Esophageal biopsy is the only objective method to obtain a definitive diagnosis and should be performed in every patient with an esophageal motor disorder evaluated for dilatation of the cardias and, if negative, it should be repeated when malignancy is suggested by available data. PMID- 8452699 TI - [Acute cholecystitis: an evaluation of the factors that determine the start of surgical treatment]. AB - The authors studied 100 acute cholecystitis treated between 1984 and 1990. In 71.4% of the cases it was associated with gallstones and 28.6% were primary acalculous cholecystitis. Two percent were postoperative. 77 patients underwent surgery. 14.3% needed an emergency operation due to acute abdominal syndrome and sepsis. In the remaining patients, the surgical procedure was performed days or weeks later according to the course of the disease, the surgeons criteria, and family and social-labour conditions. Based on these criteria, 31.7% had surgery during the first week, 23.8% in the second and 44.5% in the third or later. Cholecystectomy was the surgical procedure performed in 98.7% of the cases. Morbidity rate was 11.6% and mortality 3.9%. Analysis of morpho-clinical grades has been done in relation with the type of cholecystitis, the clinical symptoms and the course of the disease. Finally the different factors used to argue for an early or delayed surgical treatment are discussed. PMID- 8452700 TI - [Congenital cysts of the choledochus]. AB - We describe six cases of congenital choledochal cyst of the Toddani type I. All were female, with a mean age of 33.5 years (16-52). The onset of symptoms ranged 8-192 months (mean 92.8), with an unexpected finding. Ultrasound scan was performed in five patients, with two accurate diagnoses, one suspicious and two wrong results. In two cases a C.T. was performed and the diagnosis was confirmed in both. A cholelithiasis was associated in four cases. Four patients (66.4%) were treated by cyst excision, Roux-en-Y hepaticojejunostomy and cholecystectomy, three of them as a primary procedure, and one more after failure of some derivative operations. All evolved well but one, requiring sphincterotomy and Wirsungtomy. Two patients (33.6%) were treated by cholecystectomy only, with a favourable evolution. Nevertheless, we emphasize the good results achieved with cyst excision and we recommend it as the procedure of choice. PMID- 8452701 TI - [Vascular compression of the duodenum related to a plaster cast (the cast syndrome)]. AB - Case report of a 15-year-old girl presenting compression of the duodenum by the superior mesenteric artery, occurring after the application of a body plaster cast for correction of a idiopathic thoracic scoliosis, which required a gastrojejunostomy. The clinical and radiological pictures of this case fall into the rare entity called the "cast syndrome". The salient features of this syndrome are commented. PMID- 8452702 TI - [Digestive hemorrhage as the first symptom of a rupture of an abdominal aortic aneurysm]. AB - Primary aortoduodenal fistula is an uncommon complication of abdominal aortic aneurysm and is a rare cause of gastrointestinal bleeding. A case of primary arterioenteric fistula due to the rupture of an abdominal aortic aneurysm into the third portion of the duodenum is presented. Aneurysmectomy, duodenal repair, and extra-anatomic revascularization of the legs was performed. Diagnosis of primary aortoenteric fistula is difficult. The usual explorations are not demonstrative, and exploratory laparotomy is often mandatory. PMID- 8452703 TI - [Ectopic ascites secondary to the implantation of a LeVeen shunt]. AB - Insertion of a peritoneovenous shunt is an effective method of treatment of refractory ascites although not free of complications. The incidence of them varies between 20-50%, being obstruction, infection and disseminated intravascular coagulation the more frequent. We report a case of a patient that presented with ectopic ascites in cellular subcutaneous tissue one year after the placement of the shunt. This complication was due to an increase of ascites. Treated with paracentesis the ascites decreased and the ectopic ascites resolved. PMID- 8452704 TI - [A patient with Mirizzi's syndrome. The diagnostic and therapeutic considerations]. AB - A 35-year-old woman presented with a 4-month history of jaundice and pruritus. Endoscopic retrograde cholangiography (ERC) showed a partially obstructed common hepatic duct with a smooth and curved laterally based compression defect having the appearance of being secondary to an impacted gallbladder stone. Gallbladder filled with contrast medium but the cystic duct was not visualized, thus suggesting cholecystobiliary fistula formation. According to these radiologic findings, the diagnosis of Mirizzi syndrome was made. We discuss differential diagnosis, therapeutic aspects and the importance of preoperative diagnosis. PMID- 8452705 TI - [The usefulness of reactive protein C in managing patients with ulcerative colitis and Crohn's disease]. AB - Serum concentrations of C-Reactive protein (CRP) were measured in 40 patients with inflammatory bowel disease (22 with ulcerative colitis and 18 with Crohn's disease). In the evaluation of disease activity, CRP was a more sensitive (98.6% vs 71.4%) and specific (95% vs 84.6%) activity index in Crohn's disease than in ulcerative colitis. The CRP concentrations were significantly higher in Crohn's disease (57.7 +/- 55.7 mg/dl) than in ulcerative colitis (16.3 +/- 18.8 mg/dl), particularly in severely affected patients (104.8 +/- 54.3 vs 29 +/- 24.2 mg/dl). The CRP levels correlated significantly with clinical activity indices. There was poor or no correlation between CRP levels and the endoscopic activity indices, the extent of inflammatory bowel disease, and the days of hospitalization. We conclude that the determination of CRP levels provide a simple objective index of inflammatory activity with may be useful in the assessment, management and study of inflammatory bowel disease. PMID- 8452706 TI - [Splenic rupture in the course of pancreatitis]. AB - We present the case of a young patient with a history of alcoholism and chronic relapsing pancreatitis, who developed an associated pseudocyst. During the course of the disease he presented an acute abdomen due to splenic rupture and splenic thrombosis, disclosed by laparotomy. Following splenectomy and drainage the evolution was satisfactory. In the present paper we discuss the presentation of splenic vein thrombosis and splenic rupture as a rare complication of pancreatic pseudocyst. PMID- 8452707 TI - [An antro-bulbar fistula (double pylorus)]. PMID- 8452708 TI - [An abscess of the stomach wall]. PMID- 8452709 TI - [The effect of a single nighttime dose of zinc acexamate (ZAC) on basal and pentagastrin-stimulated gastric secretion]. PMID- 8452710 TI - [Gastric ascariasis in a gastrectomy patient]. PMID- 8452711 TI - [Hepatic metastases following the endoscopic polypectomy of a polyp from the sigmoid colon with an adenocarcinoma]. PMID- 8452712 TI - [Achalasia and focal nodular hyperplasia. A chance or related association]. PMID- 8452713 TI - Wrist arthrography. AB - The ligaments of the proximal row of carpal bones and the triangular fibrocartilage (TFC) strongly influence the function and stability of the wrist. Injury to the ligaments may result in chronic wrist pain or instability. Wrist arthrography is valuable in the investigation of such damage when surgical intervention is considered and plain radiography is unrewarding. There are also several technical modifications of the standard radiocarpal arthrography available. Owing to the possibility of congenital perforations and degenerative changes in these ligaments the arthrographic findings should be related to the clinical signs and the age of the patient. CT has less diagnostic importance in this respect while MR imaging is an alternative and may become the method of choice. Both these methods have great potential in the evaluation of soft tissues of the wrist other than the TFC. PMID- 8452714 TI - Radiographic assessment of coxarthrosis following slipped capital femoral epiphysis. A 32-year follow-up study of 151 hips. AB - In all, 108 patients (151 hips) previously treated for slipped capital femoral epiphysis (SCFE), were evaluated radiographically for assessment of coxarthrosis at an average age of 47 years. Five projections were obtained of each hip (supine a.p., supine modified frog lateral, standing a.p., standing anterolateral oblique, and standing posterolateral oblique) and the superior, anterior, and posterior joint space heights were measured (abnormal: superior < or = 3.0 mm and/or anterior and/or posterior < or = 2.5 mm). Sixty-three hips (42%) had joint space narrowing in at least one projection. The standing a.p. and 2 lateral oblique views identified 54 hips as abnormal, and the supine a.p. and modified frog lateral views uncovered an additional 9. The supine a.p. view was the least helpful; 12 abnormal hips on the standing a.p. view were normal on the supine a.p. view. Isolated narrowing in the anterior and/or posterior joint space was found in 9 hips (6%). These changes could only be assessed by the 2 lateral oblique views. Our results illustrate that a combination of standing radiographs, visualising the circumference of the articular space of the hip joint, and modified frog lateral projections is necessary to fully identify coxarthrosis in hips previously treated for SCFE. PMID- 8452715 TI - Low-field strength magnetization transfer contrast imaging of the patellar cartilage. AB - The time-dependent saturation transfer (TDST) method was applied at 0.1 T in order to evaluate the magnetization transfer contrast (MTC) of the patellar cartilage in vivo. Nine knees were examined. The MTC image of the knee is also demonstrated. The MTC of 63% of the patellar cartilage was attained. Magnetization transfer MR imaging may be of additional help in the evaluation of cartilage disorders at low-field MR imaging. PMID- 8452716 TI - Lumbar herniated disk mimicking neurinoma. Case report. PMID- 8452717 TI - Clinical stage I carcinoma of the cervix. Value of MR imaging in determining invasion into the parametrium. AB - Using MR imaging with a body coil parametrial invasion was determined prospectively in 169 consecutive patients considered on the basis of clinical examination to have carcinoma confined to the cervix. After radical hysterectomy correlation with histologic examination was performed for the left and right parametrium separately. The criterion for parametrial invasion was a high-signal intensity lesion with disruption of the full thickness of the cervical stroma combined with areas of abnormal signal intensity within the parametrial region on T2-weighted images. Histologic examination showed that 18 parametria in 13 patients were invaded by tumor. MR had an overall accuracy of 93%, a sensitivity of 89%, and a specificity of 93% in demonstrating parametrial involvement. Positive and negative predictive values were 43% and 99%. The main weakness of MR was 21 false-positive tests. This represents a limitation when MR is performed with a body coil. PMID- 8452718 TI - Radiographic evaluation of the urethral Kock ileal bladder substitute. AB - Fifty male patients who had undergone bladder substitution with a urethral Kock pouch after radical cystectomy for bladder cancer, were evaluated in the immediate postoperative period by retrograde pyelography and pouch cystography, and at later follow-up by pouch cystography. Other radiologic procedures (urography, ultrasonography, CT, etc.) were not part of a routine program, but were used when clinically indicated. In 12% a ureteroileal anastomotic leakage was found; the leaks resolved with continued ureteral stenting. Extravasation at the anastomosis between the pouch and the urethra was seen in 55% at the first cystography. It resolved within one month in all cases by simply leaving a catheter in the bladder. On the late cystograms reflux was observed in 6% of patients, whereas stone formation in the pouch was not encountered. A careful radiologic follow-up of patients with urinary diversions is essential to minimize postoperative complications. PMID- 8452719 TI - Accuracy of CT arterial portography of the liver compared with findings at laparotomy. AB - To evaluate the accuracy of CT arterial portography (CTAP) of the liver, CTAP examinations from 111 patients were retrospectively reviewed and compared with the findings at laparotomy. Laparotomy had been performed within 3 weeks after the CTAP examination. In cases of resectable liver tumor, the result from the pathologic examination report was used to calculate the accuracy of CTAP. In cases of nonresectable liver tumor or liver without tumor, CTAP findings were compared with the result of a thorough inspection and palpation of the liver. The right liver lobe and the medial and lateral segments of the left lobe were separately evaluated. Thus, a total of 333 lobes/segments were evaluated. Tumor was found at laparotomy in 80 of 333 lobes or segments. At CTAP a total of 94 lobes were evaluated as positive for tumor growth, 23 of these were falsely interpreted as positive and 9 were falsely interpreted as negative when compared with the findings at laparotomy. However, 3 patients called false-positives later turned out to be true-positives since the lesions were overlooked at operation. A sensitivity of 89%, a specificity of 91%, and an accuracy of 90% was calculated for CTAP. It is concluded that CTAP has a higher accuracy than other radiologic methods and should be considered suitable for preoperative evaluation of potentially resectable liver tumor. PMID- 8452720 TI - Sclerotherapy of edematous gallbladders with different agents. An experimental study in pigs. AB - Different sclerosing agents were tried in experiments with 32 pigs to achieve ablation of gallbladders rendered edematous by mechanical lithotripsy with the Rotolith lithotriptor. In 16 pigs sclerotherapy was performed with 6% acetic acid, Carnoy's solution, 95% ethanol + 3% sodium-tetradecylsulfate (STS) and hot metrizoate, respectively. These animals were sacrificed immediately after the procedure. Histologic examination showed persistent surface epithelium and glandular epithelium in all specimens. In 6 pigs, the sclerotherapy was done with Carnoy's solution, 95% ethanol + 3% STS and hot metrizoate, respectively, and the pigs were killed 6 days later. Fibrosis of the gallbladder remnants was seen in these animals, but also remnants of surface and glandular epithelium. Hot metrizoate was used in another 10 pigs and these animals were sacrificed after 8 weeks. At histologic examination fibrosis was seen in the gallbladder remnants of 9 surviving animals, but also areas of preserved muscular layer, and development of mucinous cysts were found in more than 50% of the specimens. Thus, none of the sclerosants was able to produce a total ablation of the gallbladder mucosa. PMID- 8452722 TI - MR angiography of in situ and transplanted renal arteries. Early experience using a three-dimensional time-of-flight technique. AB - Three-dimensional (3D) time-of-flight (TOF) MR angiography (MRA) was performed in 34 patients with suspected renal artery disease. In situ (i.e., nontransplanted) renal arteries were studied with MRA in 14 patients. Of these, 12 had conventional angiography for comparison. Twenty-four MRAs of transplanted renal arteries were obtained in 20 patients; 8 of these had angiography as well. Significant stenoses of in situ renal arteries were diagnosed with a sensitivity of 100% and a specificity of 95%. The stenoses were all proximal; 3D TOF MRA proved inadequate for depiction of peripheral renal arteries. MRA and angiography showed good agreement between findings in 7 of 8 patients with renal transplants. In one patient with a renal transplant, MRA showed a significant stenosis of the arterial anastomosis which appeared completely normal at i.a. DSA, indicating that findings at MRA still need to be confirmed by more established alternative methods. PMID- 8452721 TI - Peliosis of the spleen associated with a paraganglioma. Case report. AB - We report a case of splenic peliosis imitating metastases on CT. The patient was a 44-year-old man who previously had a retroperitoneal paraganglioma surgically removed. Peliosis must be considered a potential differential diagnosis of hypodense foci of the spleen seen on CT. PMID- 8452723 TI - Intravascular ultrasonographic assessment of thrombus formation on central venous catheters. AB - In vitro experiments were performed in order to investigate the appearance of different types of central venous catheters at intravascular ultrasonography. The experiments were repeated with artificially produced thrombi which were made adherent to the catheter wall. All thrombi larger than 1 mm could be identified. In a clinical study including 12 patients who had a central venous catheter, transfemoral intravascular ultrasonography was performed. The catheters had been in place for an average period of 54 days (range 1-360 days). In 3 patients a catheter thrombus, mural thrombus, or occlusive vein thrombosis was found. In 2 of these patients the catheter was occluded, in the 3rd patient it was malpositioned into the contralateral brachiocephalic vein. There were no complications following the ultrasonographic procedures. Mean catheterization time was 7.5 min (range 3-20 min). The advantages of this new method compared with conventional phlebographic studies and its impact on further clinical investigations are discussed. PMID- 8452724 TI - In vivo fluorescence microscopy of microcirculation in the renal cortex of mice. Part I. An experimental model for contrast media studies. AB - An experimental model using in vivo fluorescence microscopy for studies of renal cortical blood flow was tested in 40 mice. The model was suitable for testing a wide variety of hypotheses concerning alterations in renal cortical blood flow, including the possibility of inhomogeneous capillary blood flow distribution in response to i.v. infusions. The experimental model was tested for the effects of i.v. infusion of mannitol (0.3 mol/l). Effects of anesthesia and mechanical kidney fixation on renal cortical blood flow were studied. Neuroleptic analgesia was less hazardous to the animals than pentobarbital. Due to artifacts from respiratory and peristaltic motion, it was not possible to use neuroleptic analgesia without mechanical kidney fixation. A rating scale was designed for evaluating the capillary blood flow. The correlation between repeated ratings by the same observer was 0.806 and between 2 different observers 0.59. PMID- 8452725 TI - In vivo fluorescence microscopy of microcirculation in the renal cortex of mice. Part II. Effects of mannitol and contrast media infusions. AB - In vivo fluorescence microscopy was used for experimental studies of renal cortical microcirculation in 46 mice. The cortical circulation was studied after i.v. infusions of mannitol of various osmolalities as well as nonionic low osmolar (iohexol) and ionic high osmolar (metrizoate) contrast media. All infusions produced an increase in the number of capillaries with increased blood flow, significantly more pronounced after the infusion of iohexol, metrizoate and mannitol 1.46 mol/l than after the infusion of mannitol 0.3 mol/l. However, the renal cortical blood flow was inhomogeneous with respect to different capillaries. While the blood flow was increased in some capillaries it was to some extent simultaneously decreased in others, significantly more after infusion of metrizoate than after infusion of mannitol 0.3 mol/l. PMID- 8452726 TI - Observer variability of radionuclide left ventricular volume determination at rest and during exercise. AB - The reproducibility expressed as the intra- and interobserver variation in the determination of cardiac left ventricular (LV) volumes by the radionuclide multigated equilibrium technique in the upright position is presented. No systematic difference was found in the reproducibility between LV volumes determined in healthy subjects and cardiac patients or between examinations performed at rest and during exercise. The intra- and interobserver variation were of the same magnitude. SD of the difference was 8 to 9 ml for LV end diastolic volume, 4 to 7 ml for LV end-systolic volume, and 2 to 5% for LV ejection fraction. Thus, there is a 95% probability that repeat measurements, either by the same observer or by 2 independent observers, will result in the same LV end-diastolic volume within 18 ml, LV end-systolic volume within 11 ml, and LV ejection fraction within 8%. Only 15% of the variation can be ascribed to determination of the attenuation correction factor. PMID- 8452727 TI - RES scintigraphy in polycythemia vera and secondary or relative polycythemia. AB - Scintigraphy of the reticuloendothelial system (RES) was performed in 19 patients with polycythemia vera (PCV) and in 18 with secondary or relative polycythemia (PS). Bone marrow extension was found in all patients with PCV and in 11 of 18 patients with PS. The patients with PCV had a higher degree of extension than those with PS. Increased pelvic bone marrow activity was found in 16 of 19 PCV patients, but in none with PS. Splenomegaly was found in 9 patients with PCV, and in none with PS. It is concluded that RES scintigraphy in the majority of patients may differentiate between PCV and PS using the parameters pelvic bone marrow activity, bone marrow extension and splenic size. PMID- 8452730 TI - A double-guide-wire technique in renal angioplasty. A modified approach. PMID- 8452729 TI - CT measurement of mediastinal anterior junction line in emphysema patients. AB - The anterior junction line (AJL), the sterno-aortic distance and the sagittal thoracic diameter were measured in CT sections at the carinal level in 22 patients with emphysema and 22 controls. The measured distances were all significantly larger in the emphysema patients. An AJL of 3 cm or more and a sterno-aortic distance of 4 cm or more was found in respectively 10 and 16 of the 22 emphysema patients but in none of the control patients. PMID- 8452728 TI - Oral magnetic particles. Results from clinical phase II trials in 216 patients. AB - Oral magnetic particles (OMP) have been evaluated in a clinical phase II trial program comprising 216 patients in 7 European centers. Adult patients referred for MR imaging for various abdominal pathologies were examined. The patients received OMP at a concentration of 0.1 g/l (ultralow field) or 0.5 g/l (mid/high field) and OMP was diluted in water or in a more viscous liquid formulation. Depending on the area of interest, OMP was ingested in a volume of 300 to 800 ml. OMP was well tolerated with no serious adverse events and the patient acceptability was good. OMP had a good contrast effect on all applied pulse sequences. The viscous formulation of OMP was homogeneously distributed through the entire gastrointestinal tract without inducing disturbing susceptibility artifacts. The postcontrast diagnostic information was improved in 70% of the cases. Based on the encouraging results in phase II, OMP has been advanced to phase III clinical trials. PMID- 8452731 TI - Optical radiation-field indication in X-ray tubes with more than one focus. PMID- 8452732 TI - CT appearance of surgical sponge retained in pleura. PMID- 8452733 TI - Physiologic monitoring. PMID- 8452734 TI - Fundamentals of physiologic monitoring. AB - For centuries, medical practitioners had no electronic medical instruments and had to rely on their senses of sight, hearing, smell, taste, and touch to obtain physiologic measurements. Although it is possible to estimate blood pressure by palpating the pulse at the radial or brachial artery, such estimates are not accurate. Determining arterial oxygen saturation of hemoglobin is more complex: how "blue" a patient appears depends on skin coloration, lighting, and the examiner's sense of color. Finally, using radiographic images to validate pulmonary edema when clinicians suspect that there is an elevated left atrial or pulmonary artery wedge pressure also challenges human senses. However, today's medical instruments use transducers and signal processors to convert patient information into a form that clinicians can easily perceive and understand. This article defines terms used with biomedical instrumentation and discusses the components of ideal physiologic patient monitoring systems. PMID- 8452735 TI - Right ventricular volumetric monitoring. AB - The goal of invasive hemodynamic monitoring is to evaluate the components of oxygen delivery and consumption. Parameters obtained from the physiologic profile are used to assess and optimize oxygen delivery to meet the tissue needs of the critically ill patient. Oxygen delivery is defined as cardiac output multiplied by the arterial oxygen content. Research has demonstrated that adequate increases in oxygen delivery improve survival. The primary intervention for optimizing oxygen delivery is appropriate fluid resuscitation. Classic endpoints of adequate fluid resuscitation have been pressure-based parameters, which possess many inherent assumptions. Current clinical issues are directed toward assessment of the patient's status in relation to the oxygen supply-and-demand balance. Identification of therapeutic interventions to achieve the goal of increasing oxygen delivery are paramount. Evaluation of the role of the right ventricle (RV) in biventricular performance and incorporation of volumetric measurements to assess the critically ill patient are presented. PMID- 8452736 TI - Using continuous SVO2 to assess oxygen supply/demand balance in the critically ill patient. AB - To ensure that tissues are well oxygenated, oxygen supply and demand are now targets of therapy for the critically ill patient. This chapter reviews the physiologic determinants of oxygen supply, how it is threatened by respiratory or cardiac dysfunction or by hemorrhaged or anemic states, and how it can be assessed in individual patients. Activities and conditions that increase tissue oxygen demand are examined so that clinicians can identify those patients whose oxygen demands may be excessive and should be controlled. Failure of tissues to consume enough oxygen is explained in patients with critically low delivery or with the maldistributed blood flow state seen in sepsis. The monitoring of mixed venous oxygen saturation is examined as a method of tracking the threats to supply/demand balance and of guiding treatment that can support the adequate oxygenation of tissue. PMID- 8452737 TI - Intracranial pressure monitoring. AB - Intracranial pressure monitoring (ICP) is a technology that assists critical care nurses in the assessment, planning, intervention, and evaluation of care. The physiologic basis of intracranial hypertension (ICH) and ICP monitoring are reviewed. Types of monitors are described. Advantages, disadvantages, and complications of fluid-filled versus fiberoptic systems are explored. Priorities in nursing care of the patient with an ICP monitor are examined. PMID- 8452738 TI - Integrating the hemodynamic profile with clinical assessment. AB - Hemodynamic profiling has become common practice in critical care units. While the ability to monitor, measure, and calculate the many parameters related to cardiac output is a valuable adjunct in the care of the critically ill, it cannot be used as a substitute for sound clinical assessment. The ability to integrate the hemodynamic profile with clinical assessment is necessary if patients are to receive comprehensive critical care. In addition, assessment frameworks such as Forrester's subsets of hemodynamic compromise provide clinically useful guidance in the diagnosis and treatment of a variety of clinical challenges. PMID- 8452739 TI - Physiologic monitoring of infants and children. AB - Accurate and safe monitoring of infants and children requires knowledge of their unique physiology, especially cardiovascular function, pulmonary physiology, and metabolic function. These individual features influence the equipment selection, as well as data interpretation. Although some adult equipment is adaptable for pediatric use, many specifications must be tailored to pediatric needs. Vascular monitoring in pediatric patients requires specific knowledge of insertion procedures and complications, fluid maintenance, and hemodynamic norms, indexed to body surface area. Valid data interpretation requires an understanding of the distinctive clinical responses intrinsic to the pediatric patient. Likewise, maintenance care for pediatric patients always includes attention to precise fluid balance, thermoregulation, and metabolic needs. Finally, all pediatric patients require constant vigilance to protect the integrity of their monitoring systems and, ultimately, the safety of these patients. Failure to address these concerns may result in complications or invalid data. PMID- 8452740 TI - Quality assurance in hemodynamic monitoring. AB - Patient care management decisions frequently are based, at least in part, on hemodynamic indices. Accuracy in repeated measurement of hemodynamic parameters is therefore critical. It can be achieved only through a program of quality assurance (QA), which should include the following factors: static, dynamic, and validation of pulmonary artery wedge pressure (PAWP). The static QA factor consists of establishing an accurate reference point from which all subsequent measurements are made. The hemodynamic monitoring system must be able to transmit pulsating physiologic pressures to the transducer with high fidelity, which is validated via the dynamic response or "square wave" test and damping coefficient. Other QA aspects that are used to validate the accuracy of PAWP include catheter placement into lung zone 3 capillary and comparison of capillary to arterial blood gases. Measurement error also can be introduced because of varying methods to quantify the ana-log pressure waveforms, such as end-expiratory or pressure averaging techniques. This paper explores each of these domains within a framework of quality assurance. PMID- 8452741 TI - Bedside electrocardiogram monitoring. AB - A recent national survey of critical care nurses reveals that the leads many nurses select to monitor their patients are diagnostically inferior to other available leads, and that lead placement often is inaccurate. This article reviews the best leads for electrocardiographic (ECG) monitoring, illustrates their accurate placement, and explains reasons for the dilemma in current practice. Questions relevant to practicing nurses are addressed, including 1) Is lead MCL1 as good as V1? 2) When is it appropriate to substitute lead MCL1 for V1? and 3) How important is it for electrodes to be placed exactly in specific anatomic locations? Finally, a case study is provided to illustrate how accurate monitoring can prevent misdiagnosis and resultant inappropriate therapy. PMID- 8452742 TI - ST segment monitoring for myocardial ischemia. AB - Many patients in the critical care unit (CCU) are at risk for myocardial ischemia and acute coronary artery reocclusion. The use of continuous ST segment monitoring detects transient and sustained ischemia, despite the absence of symptoms, more completely than rate and rhythm monitoring alone. The accuracy and sensitivity of the ST segment for detection of ischemia is dependent on the number and location of the electrocardiographic leads used in conjunction with the site of obstruction. Thus, when using ST segment monitoring for detection of ischemia, one of the most important decisions for the nurse to make is lead selection. In addition, both ischemic and nonischemic ST segment changes must be considered. PMID- 8452743 TI - Monitoring body temperature. AB - Vigilant and accurate assessment of thermal balance is imperative with the critically ill. Disease, injury, or pharmacologic activity can impair thermoregulation, leaving patients vulnerable to uncontrolled gain or loss of heat. Body temperature provides cues to onset of infection, inflammation, and antigenic responses, as well as indicating efficacy of treatment. With knowledge of heat transfer principles, physiologic processes that distribute body heat, and principles of thermometry, the nurse is better equipped to make reasoned clinical judgment about this important vital sign. Choices of instruments or measurement sites are influenced by needs to estimate either hypothalamic temperature or shifts in body heat. Need for continuous versus episodic assessment, availability or intrusiveness of equipment, and stability of the patient also influence choices. Monitoring devices, measurement sites and techniques, equipment limitations and precautions are discussed. Interpretation and application of assessment findings are presented as they relate to abnormally high or low temperatures, patterns of fever, and temperature gradients. PMID- 8452744 TI - Respiratory monitoring in critical care. AB - The assessment of pulmonary function, from a clinical perspective, can be performed accurately only if the clinician understands the concept ventilation/perfusion ratios of the lung. The major categories of ventilation/perfusion ratios are intrapulmonary shunting and physiologic deadspace. Virtually all pulmonary assessments and interventions are aimed to address Qs/Qt or Vd/Vt. This chapter provides background information useful to the clinician in the assessment of intrapulmonary shunting and deadspace analysis. From this information, more thorough assessments of pulmonary function are possible. PMID- 8452745 TI - Arterial blood pressure measurement technique. AB - Arterial blood pressure (BP) measurements, which include invasive direct methods and noninvasive indirect methods, provide a picture of the hemodynamic status of the patient. Invasive BP methods measure pressure pulse wave amplitude; noninvasive methods rely on blood flow or arterial wall motion as a basis for the determination of BP values. To obtain the most accurate BP value, the clinician must identify which measurement variables in a specific clinical situation are most contributory to error and, if possible, use a method of measurement for which the sources of error are not parallel. Blood pressure values obtained by different methods cannot be compared without a thorough understanding of the user related and instrumentation-related limitations associated with each BP measurement technique. PMID- 8452746 TI - Cardiac output determination. AB - Critical care nurses frequently are involved in obtaining cardiac output measurements and in using these data to assess and to plan therapy. This article reviews the physiologic determinants of cardiac output and the clinical factors that influence these determinants. Principles and techniques of common methods of cardiac output measurement are discussed. A thorough presentation of guidelines for troubleshooting problems with thermodilution cardiac output measurement is provided in a table. Nursing management issues are discussed using relevant nursing research. Future considerations in cardiac output measurement are discussed, and suggestions of an ideal cardiac output system are provided. PMID- 8452747 TI - Pulmonary artery pressure monitoring. AB - Critical care nurses often care for critically ill patients who require pulmonary artery catheterization. Nurses need an extensive knowledge base to understand the various technical and physiologic factors that may affect the accuracy of pressure measurements. Continued nursing research is needed to refine and guide the development of nursing practice standards in caring for patients who require pulmonary artery pressure monitoring. PMID- 8452748 TI - Clinical practice guidelines. Pressure ulcers in adults: prediction and prevention. Panel for the Prediction and Prevention of Pressure Ulcers in Adults. AB - This clinical practice guideline makes specific recommendations for identifying at-risk adults and for defining early interventions for preventing pressure ulcers. The guideline may also be used to treat Stage I pressure ulcers (nonblanchable erythema of intact skin). These guideline recommendations are not intended as the basis of care of infants and children, nor do they apply to individuals with existing Stage II or greater pressure ulcers or to individuals who are fully mobile. PMID- 8452749 TI - Photopheresis for ARC: a nursing perspective. AB - Photopheresis, an approved treatment for cutaneous T-cell lymphoma (CTCL), is the basis of a trial involving patients with AIDS-related complex (ARC). This study has provided the opportunity to identify unique nursing challenges along with satisfaction from innovative nursing interventions. PMID- 8452750 TI - What's your assessment? Varicella. PMID- 8452751 TI - Diagnosis of lower-extremity ulcers. AB - The prevalence of lower-extremity ulcers is expected to increase as the U.S. population ages. Although these ulcers are often difficult to diagnose, the proper etiologic diagnosis can be useful in guiding treatment. PMID- 8452752 TI - HIV and associated cutaneous diseases. AB - HIV infections manifest a wide spectrum of dermatologic diseases. These can be classified and described as primary bacterial infections, fungal infections, associated cutaneous disorders, and hypersensitivity reactions. The presentation of each disease can be clearly identified, and current preferred medical therapies recommended for each disorder. PMID- 8452753 TI - The current and future role of the nurse in phlebology: the Canadian experience. AB - Sclerotherapy treatment of varicose and telangiectatic leg veins is becoming a popular treatment in North America. Since the tools for performing this treatment are inexpensive and readily available, many health care practitioners are performing this technique with variable states of expertise and outcome. Understanding the professional and ethical issues facing phlebology nurses in Canada can enhance the care of phlebology patients in the United States. PMID- 8452754 TI - Mammalian gonadotropin-releasing hormone increases PGF2 alpha production activating diacylglycerol lipase in Rana esculenta interrenal. AB - The aim of the present paper was to clarify if the prostaglandin F2 alpha (PGF2 alpha) production stimulated by mammalian gonadotropin-releasing hormone (mGnRH) comes from arachidonic acid (AA) freed by diacylglycerol (DAG) and/or membrane phospholipids in the interrenal of Rana esculenta. Interrenals of Rana esculenta were incubated with inhibitors of phospholipase A1 (PLA1), phospholipase A2 (PLA2), phospholipase C (PLC), protein kinase C (PKC) and diacylglycerol lipase (DAGlipase) in the presence or absence of mGnRH. In parallel, the same experiments were carried out using [3H]AA-labelled interrenals. The results of the experiments with non-labelled and [3H]AA-labelled interrenals were in agreement. PLA1, PLA2, PLC, PKC and DAGlipase inhibitors induced a decrease in PGF2 alpha production in interrenals without mGnRH, and PLA2 inhibitor was more effective than other inhibitors. PLC and DAGlipase inhibitors decreased the PGF2 alpha production by interrenals incubated with mGnRH, and PLC inhibitor was more effective than DAGlipase inhibitor. These findings suggest that the main source of AA used for mGnRH-induced PGF2 alpha synthesis is DAG; probably this decapeptide increases PGF2 alpha production enhancing the DAGlipase activity. PMID- 8452755 TI - Arrestin-subtypes in insect antennae. AB - Arrestin is supposed to be involved in uncoupling receptor-mediated second messenger cascades. Clones encoding proteins homologous to arrestin have been isolated from antennal cDNA libraries of Locusta migratoria and Heliothis virescens. Based on the size and several characteristic motifs, the two proteins are considered as members of different arrestin subfamilies. One of the subtypes, which has also been found in Drosophila, lacks the regulatory acidic C-terminal. The putative site of interaction with phosphorylated receptors, a cationic region in the primary structure, is conserved in all identified arrestins from locust to human. PMID- 8452756 TI - Differential effects of fluoride and a non-hydrolysable GTP analogue on adenylate cyclase and G-proteins in Ceratitis capitata neural tissue. AB - We have examined the effects of fluoride on guanine nucleotide-binding regulatory proteins (G-proteins) in neural membranes from the dipterous Ceratitis capitata. Fluoride effects on the Gs-protein were monitored by determining adenylate cyclase activity and cholera toxin-catalysed ADP-ribosylation whereas those on the G(o)-protein were studied by measuring ADP-ribosylation with pertussis toxin. Data are discussed in relation to the effects of a non-hydrolysable GTP analogue. G-protein activation carried out by fluoride seems not to mimic, at least in insects, activation by non-hydrolysable GTP analogues, in opposition to that proposed for transducin, the G-protein of the mammalian visual system, and other G-proteins. PMID- 8452757 TI - Adenine dinucleotide-mediated activation of glycogen phosphorylase in isolated liver cells. AB - The ability of purine nucleotides (e.g. ATP) to cause a dose-dependent activation of glycogen phosphorylase in isolated liver cells is well known. These agents mediate their effects through interaction with specific P2-purinoceptors in the plasma membrane. We have investigated the ability of a range of synthetic and naturally occurring adenine dinucleotides to cause a similar stimulation of glycogen phosphorylase activity in isolated rat liver cells. Our results indicate that Ap3A and Ap4A, the most abundant naturally occurring adenine dinucleotides, cause a dose-dependent activation of glycogen phosphorylase similar to that observed with ATP. Similar responses were seen with Ap5A, Ap6A and a series of phosphorothioate analogues. In contrast, the response to phosphonate analogues depended on the position of the P-C-P bridge. The dinucleotides appear to exert their effects directly, rather than through hydrolytic products such as adenosine and/or ATP. The possibility that adenine dinucleotides are physiologically significant extracellular purinergic effectors is discussed in the light of these observations. PMID- 8452758 TI - rho gene products, botulinum C3 exoenzyme and cell adhesion. PMID- 8452759 TI - Hemorrhagic transformation after cerebral ischemia: mechanisms and incidence. AB - Hemorrhagic infarction and cerebral hematoma are feared events that may follow cerebral ischemia. Newly developed thrombolytic agents may be effective stroke therapy, but may also promote hemorrhagic complications after ischemic stroke. It is therefore critically important to understand the true incidence of hemorrhagic transformation after ischemic stroke, and to identify if possible the mechanisms underlying the phenomenon. In recent years, studies using serial computed tomography to identify hemorrhage have shown that transformation occurs in 15 to 43% of patients presenting with ischemia. Experimental and clinical evidence support the notion that hemorrhage results from augmented collateral circulation into the ischemic zone, perhaps in concert with hypertension. Recanalization and distal migration of the thrombus are not factors that are associated with transformation. Pharmacologic recanalization using thrombolytic drugs are not likely to be associated with hemorrhage if reperfusion is accomplished very soon after the onset of neurologic symptoms. PMID- 8452760 TI - Cerebral protective effects of etomidate: experimental and clinical aspects. AB - Reduction of cerebral blood flow below a critical threshold for a protracted time interval results in irreversible metabolic events culminating in cell death. The development of agents capable of extending the tolerable ischemic interval is of great importance as such agents may allow time for therapeutic measures to be accomplished which could restore cerebral perfusion. This issue is of particular pertinence in the treatment of complex cerebrovascular diseases when local (or global) cerebral blood flow must be interrupted during vascular reconstruction. Thiopental achieved great popularity once protective properties were demonstrated experimentally. Unfortunately, serious cardiovascular depression associated with high-dose barbiturates as well as prolonged duration of action may decrease collateral flow and limit their utility. Etomidate is a nonbarbiturate carboxylated imidazole which is capable of similar cerebral metabolic suppression without significant cardiac side effects. Accumulating experimental evidence supports the protective properties of this drug and suggests that it may be valuable clinically for this purpose. Significant adrenal suppression is a major toxic effect that must be treated if large doses or protracted administration is planned. PMID- 8452761 TI - The cerebrovascular parasympathetic innervation. AB - Until recent years, little has been known about the parasympathetic innervation of cerebral vessels, in contrast to the sympathetic innervation. Recent histochemical and biochemical studies on cerebrovascular parasympathetic nerves have revealed their sources and pathways. Histochemical studies have demonstrated nerve fibers containing choline acetyltransferase, a reliable marker for cholinergic nerves, and vasoactive intestinal polypeptide (VIP) in the cerebral vessels. By combining histochemistry with a retrograde tracer technique and selective denervations, the cerebrovascular parasympathetic innervation has been mapped in the rat, cat, and monkey. Acetylcholine (ACh) has been measured biochemically in the pial arteries of several species. A high-affinity uptake, local synthesis, and tetrodotoxin-sensitive release of ACh have been demonstrated in the pial vessels. Pharmacological studies on isolated pial arteries have revealed ACh- and VIP-induced relaxation through the stimulation of muscarinic and VIPergic receptors, respectively. The action of ACh requires an intact endothelial function. An increase in cerebral blood flow upon stimulation of pre- or postganglionic fibers of the sphenopalatine ganglion has been demonstrated in some animals, and can be mimicked by local administration of ACh and VIP in vivo. This indicates a role of the parasympathetic nerves in tone regulation of the cerebral vessels. The pathophysiological conditions during which these nerves become activated are currently being revealed. PMID- 8452763 TI - Clinical, laboratory, and radiographic assessments. AB - Version 2 of the Arthritis Impact Measurement Scale (AIMS2), together with the Medical Outcomes Study 36-Item Short Form Health Survey provide two state-of-the art health-status instruments. The Medical Outcomes Study can be used in all illnesses, including rheumatic diseases. The AIMS2 incorporates new items concerning work status, satisfaction, attribution of problems to arthritis, and self-designation of priority areas for improvement. Measure of osteoarthritis and ankylosing spondylitis and review of the measures used to assess these illnesses were comprehensively evaluated, and data on reliability, sensitivity to change, sample size, and clinically significant change were provided this year, supplying an invaluable resource for trialists and clinicians. PMID- 8452762 TI - Epidemiology of the rheumatic diseases. AB - Emerging osteoarthritis studies suggest that certain occupations are associated with a high risk for development of hip and knee osteoarthritis, at least in men. The main activities identified are regular lifting for the hip and knee bending for the knee. Obesity is a well-known risk factor for the knee, and it has been suggested that this risk can be halved by losing weight. Studies of the natural history of knee osteoarthritis suggest that many individuals do not develop osteoarthritis, although precise prognostic indicators are lacking at present. No new etiologic information on rheumatoid arthritis has appeared recently, although hormonal and reproductive factors in women continue to be studied with variable results. Agreement is slowly being reached on how to define vertebral fractures for epidemiologic study, which should produce more consistent results. In a study from Rochester, Minnesota, US incidence rates were produced for clinically diagnosed vertebral fracture (117/100,000) that are similar to hip rates, although they occur at an earlier age. Continued study of risk factors continues to show them to be of little use in screening. In systemic lupus erythematosus, hair dyes have not been confirmed as a risk factor, although there may be a link with domestic pets. There are conflicting data on the roles of obesity and occupational factors in carpal-tunnel syndrome. PMID- 8452764 TI - Clinical trials in rheumatology. AB - The randomized controlled trial continues to be the standard for evaluating the clinical utility of new procedures or treatments. The randomized controlled trial seems to affect the clinical practice of physicians. Although the design of the randomized controlled trial is well described, consideration should be given to the questions asked and whether the trial is conducted and analyzed so that the questions can be answered. Comparative trials have become more frequent than placebo trials in the past decade, and clinical research financing is falling increasingly to the pharmaceutical industry. Process and outcome measures are receiving more attention. Various groups and committees are evaluating disease activity measures to delineate a small number that can become core or foundation measures. These measures are also being defined and standardized. The process is much further advanced for rheumatoid arthritis than for other diseases, and some common and perhaps "mundane" disease states are being neglected. PMID- 8452765 TI - Rehabilitation and biomechanics. AB - In this review, we discuss large epidemiologic and focused clinical and laboratory studies published over the past year that advanced our current knowledge of the physical and functional impairments, societal handicaps, and disability related to the rheumatic diseases. Studies of rehabilitative methods appropriate for patients with a variety of rheumatic and musculoskeletal disorders are presented. PMID- 8452766 TI - Health care research in rheumatology. AB - In the first three sections of this review, studies of disability among patients with musculoskeletal conditions are discussed. Evidence continues to demonstrate that arthritis has a substantial impact on disability. Correlates of disability for patients with general musculoskeletal conditions, rheumatoid arthritis, and osteoarthritis are reviewed, as are strategies to ameliorate arthritis-related disability. The fourth section of this review highlights the importance of pain coping strategies for arthritis patients. The concluding section reviews educational strategies in the rheumatic diseases. PMID- 8452767 TI - Interplay of T lymphocytes and HLA-DR molecules in rheumatoid arthritis. AB - One of the genetic components of seropositive rheumatoid arthritis has been mapped to a short sequence stretch in the third hypervariable region of the HLA DRB1 gene. A new concept has emerged, proposing that the shared-sequence motif is functional in determining the clinical patterns of rheumatoid arthritis and the severity of the disease in a codominant mode. Patients with a double dose of the shared sequence tend to have more serious disease manifestations, suggesting a model in which the genetic element is involved in perpetuating the disease. The pathogenetic model in which the shared epitope selectively binds and presents an arthritogenic peptide appears too simplistic to account for these findings. Our understanding of how the shared epitope may contribute to forming the molecular complex of the T-cell receptor, peptide, and HLA-DR molecule is advancing. Molecular analyses of the synovial T-cell infiltrate continue to define the various components involved in recruiting T cells to the site of synovial inflammation. Adhesion molecules, predominantly the endothelial cell ligands vascular adhesion molecule 1 and endothelial leukocyte adhesion molecule 1, attract phenotypically selected T cells with a wide spectrum of specificities. The rheumatoid factor-positive B cells may be important antigen-presenting cells in the joint and may activate T cells with many different specificities. Rheumatoid factor immunoglobulin genes show clear evidence of somatic mutation, indicating a T cell-dependent, antigen-driven process. Thus, multiple factors contribute to the composition of the inflammatory infiltrate and may well modulate the repertoire of T cells recruited to the tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452769 TI - Clinical features, diagnosis, and prognosis in rheumatoid arthritis. AB - The past year has witnessed a modest expansion in our understanding of the clinical, diagnostic, and prognostic features of rheumatoid arthritis. Almost every continent has reported prevalence, phenotype, and clinical features of rheumatoid arthritis subpopulations. Reviews of the natural history and therapy of cervical spine disease, Felty's disease, and lung involvement dominate the clinical literature. Rheumatoid arthritis-like syndromes have been reported to occur after immunotherapy with interferon alfa and interleukin-2. There have been case studies on human immunodeficiency virus, cachexia, pregnancy, "pseudosepsis," bone loss, and malignancy in rheumatoid arthritis. Diagnostic criteria and new classifications for functional and global impairment have been published, and new health impairment questionnaires have been evaluated. Novel isotopes and the role of magnetic resonance imaging in damaged joints were discussed. Rheumatoid factor was reaffirmed as a significant prognostic variable, and the roles of immunogenetic loci, sulfur oxidation, and serum matrix proteins were evaluated in early rheumatoid arthritis. Functional status was again verified as a strong prognostic marker. PMID- 8452768 TI - New focus on treatment for rheumatoid arthritis. AB - Although the pathogenesis of rheumatoid arthritis increasingly continues to be well understood, therapeutic approaches to the disease remain relatively unsophisticated and based more on anecdote than scientific reasoning. During the past year, additional supportive data regarding the usefulness of front-line agents such as methotrexate and hydroxychloroquine were acquired, and novel potential interventions, such as pulse gammaglobulin and OM-8980 were identified. Animal model studies still support the prospect that genuine remission-inducing strategies will be realized in the future. PMID- 8452770 TI - Tumors of soft tissues and bone. AB - The recent literature pertaining to tumors of articular structures and bone is reviewed. In pigmented villonodular synovitis, the bone resorptive cell is a macrophage polykaryon rather than an osteoclast. Complete arthroscopic synovectomy was successful in most diffuse articular forms of the disease. The early synovial changes in synovial chondromatosis were described; the lesion may be difficult to distinguish from synovial chondrosarcoma. Free body removal may be sufficient to treat synovial chondromatosis. Magnetic resonance imaging has been found useful in association with plain radiographs in the diagnosis of hemangioma and synovial sarcoma. Intracapsular osteoid osteoma, a benign neoplasm, may cause chronic monoarthritis. Computed tomography is essential in the diagnosis of this lesion. Aneurysmal bone cysts frequently show fluid-fluid levels on magnetic resonance imaging. Osteosarcoma, predominantly a tumor of childhood or adolescence, may occur in individuals over age 40 with underlying bone conditions. Computed tomography and magnetic resonance imaging are complementary in defining the extent of this lesion. PMID- 8452771 TI - Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome. AB - Operational diagnostic criteria for fibromyalgia were applied to most clinical studies during the past year. Similar diagnostic criteria for chronic fatigue syndrome are being revised, but criteria for myofascial pain have not been agreed on or tested. Intense research efforts focused on the role of neurohormones and the hypothalamic-pituitary-adrenal axis in fibromyalgia and chronic fatigue syndrome over the past year. PMID- 8452772 TI - Temporomandibular disorders. AB - Temporomandibular disorders include a variety of intracapsular and extracapsular disorders that may or may not be related to each other and the diagnosis of which can be complicated. The causes of these disorders have not been identified scientifically and instead rely on anecdotal clinical experience. Preliminary epidemiologic studies have begun to identify predisposing, initiating, or perpetuating factors. Recent advances in imaging techniques have created opportunities for a more rational approach to the treatment of these disorders. Nonsurgical therapies are used to manage most of these disorders. Refinements in surgical procedures have increased the predictability of results for patients who have followed nonsurgical treatments. Arthroscopy has added to the macroscopic and microscopic knowledge of intracapsular disorders and offers a less invasive approach to surgical management. With proper diagnosis and treatment selection, quality of life of the majority of patients can be improved. PMID- 8452773 TI - Perspective on low back pain. AB - Low back pain is a common and expensive ailment among the working population. Despite the increasing amount of basic and clinical knowledge on low back pain, the precise causes of almost all cases cannot yet be defined. The tissues that could be the sources of pain in the low back have been better identified. The validity of the commonly used diagnosis of facet syndrome is now being questioned, and a favorable response to injection of the facet joints should not be considered an indication for posterior lumbar fusion. Studies continue to indicate that total body vibration and cigarette smoking have a relationship to disk degeneration. Improved imaging techniques such as computed tomography and magnetic resonance imaging allow better visualization of the pathology in the vertebral column, but the correlation between these imaging findings and clinical symptoms has yet to be proven. Psychosocial factors are now recognized as important in patients with low back pain. Surgical procedures, even when appropriately indicated, have produced no better result than has the natural course of the condition. PMID- 8452775 TI - Epidemiology and health services research. PMID- 8452774 TI - Peripheral nerve entrapment, occupation-related syndromes and sports injuries, and bursitis. AB - A growing interest in nonarticular rheumatic conditions has been shown recently by the large number of articles published on the subject. In this review, three nerve entrapment syndromes and problems of four tendons of the ankle region are covered. Suprascapular neuropathy is underrecognized and, in many cases, may be treated conservatively. Entrapment of the radial and ulnar nerves may be caused by a variety of conditions, some of which are unusual. Tenosynovitis and rupture of the tendons of the ankle region, including the posterior tibial, anterior tibial, peroneus longus, and Achilles tendons, are reviewed. PMID- 8452776 TI - Patients needed for clinical trials to evaluate new treatment for breast cancer. PMID- 8452777 TI - Rise in breast cancer incidence chiefly in ER-positive cancers. PMID- 8452778 TI - Current reproductive technology: considerations for the oncologist. AB - Advances in reproductive technology now afford options for certain cancer patients that the oncologist must consider when planning treatment. For men undergoing treatment likely to destroy testicular function, the development of sperm banks to store cryopreserved sperm offers the hope of future fatherhood. Cryopreserved sperm can be held indefinitely, with pregnancies via artificial insemination reported up to 15 years after freezing. For female cancer patients who will lose ovarian function but likely retain a viable womb, in vitro fertilization techniques hold the promise of pregnancy with the use of donated ova. In some cases, it may even be possible to extract the woman's own eggs before surgery and fertilize them with her husband's sperm. The resulting embryos, like sperm, can be frozen for indefinite future use. In the future, with new technological advances, extraction of ova for freezing at the time of ovarian extirpation may be a possibility. PMID- 8452779 TI - New surgical procedure to remove rectal tumors said to reduce hospital stays, complications. PMID- 8452780 TI - Clinical trials referral resource. PMID- 8452781 TI - Radiation therapy in the management of cancer of the cervix. AB - In general, reported 5-year survival rates are 85% to 90% for stage IB, about 75% for stage IIA, 60% to 65% for IIB, 25% to 50% for stage IIIB, and 10% or less for stage IV. For bulky lesions, a combination of preoperative irradiation and hysterectomy has been tried; however, in some studies the results are no better than those noted with higher doses of irradiation alone. PMID- 8452782 TI - Adjuvant treatment for rectal cancer: current status. AB - Surgery is still the cornerstone of curative treatment for rectal cancer. A combination of postoperative radiation and chemotherapy is the preferred adjuvant treatment for TNM stages II and III rectal cancer. Although studies combining 5 fluorouracil (5-FU) and the investigational agent semustine (methyl-CCNU) with radiation showed some survival benefit, preliminary results of recent studies suggest that radiation with 5-FU alone is an effective substitute. Preoperative radiation treatment has several advantages over postoperative radiotherapy. The major disadvantage, that tumors may be downstaged, preventing exact evaluation of treatment results, may be overcome by using rectal ultrasound for preoperative staging. Another promising treatment is preoperative radiation combined with 5-FU as a radiosensitizer and for possible increased systemic effect. Studies are needed to find a better, less toxic radiosensitizer, to explore new chemotherapy combinations with 5-FU (such as levamisole), and to define the proper dose sequence and integration. PMID- 8452783 TI - Dracunculiasis eradication. Update 1992. PMID- 8452785 TI - Influenza. PMID- 8452784 TI - Expanded programme on immunization. Immunization coverage against measles, mumps and rubella. PMID- 8452787 TI - Health care systems: American dream or American nightmare? PMID- 8452786 TI - Concern over nurses' lack of AIDS knowledge. PMID- 8452788 TI - Diversional therapy: musical care. PMID- 8452789 TI - Community care: where to get help. PMID- 8452790 TI - Alternative wound dressings in A&E. AB - Paraffin tulle dressings remain in common use in almost every accident and emergency (A&E) department. Dressing a wound with paraffin tulle necessitates the use of a secondary dressing which, in common practice, is almost always an absorbent pad or gauze. Such combined dressings may represent poor practice, because alternatives are now available which better satisfy the required characteristics of the optimum dressing (1). The author looks at some of the available alternatives. PMID- 8452791 TI - The implications of NVQs for nursing. AB - By December 1992, nearly 900 National Vocational Qualifications (NVQs) covering the employment functions of up to 80 per cent of the working population had come into being (1). The implications for a major employer such as the National Health Service are enormous, but nursing seems to have been slow to grasp its significance. Pat Hughes reviews the issues from practice, management and education perspectives. PMID- 8452792 TI - Hysterectomy (continuing education credit). PMID- 8452793 TI - Para-suicide: a cause for nursing concern. AB - The government has recently highlighted the tragedy of lives lost through suicide, aiming to reduce this loss by positive intervention (1). This article examines societal and nursing attitudes towards those who commit suicide or para suicide. It calls on nurses to recognise their own ambivalent feelings and argues for government intervention to eradicate many of the social factors leading to suicide. PMID- 8452794 TI - A tribute to a marvellous man. PMID- 8452795 TI - The Clay column. PMID- 8452796 TI - Computers: problems with nursing systems. PMID- 8452798 TI - Nurses work. Your campaign. PMID- 8452797 TI - Community care: honing support. PMID- 8452799 TI - Nurses work. Campaign aims and objectives. PMID- 8452800 TI - Nurses work. An insecure future. PMID- 8452801 TI - Resuscitation. Nurses' skills in basic life support: a survey. AB - Cardiopulmonary resuscitation (CPR) skills are fundamental to the function of health professionals, but studies have shown them to be inadequate and outdated. This week, Nursing Standard launches a three-part weekly series on resuscitation. Parts two and three will address the associated ethical issues and measures of outcomes and accountability. The series begins with a survey in a district general hospital which aimed to establish nurses' levels of awareness on the current recommendations for CPR laid down by the Resuscitation Council of the UK. The results show a poor knowledge level and recommendations are offered. PMID- 8452802 TI - Contact lenses and bacterial infections. AB - Research has shown that although rare, contamination of contact lenses with Acanthamoeba and other organisms after cleansing can cause severe ocular morbidity. The author reviews the research data, and offers recommendations for appropriate use of cleansing solutions. PMID- 8452803 TI - Management control systems in the NHS. AB - Non-profit organisations like the NHS require mechanisms for evaluating their performance and judging how effectively or efficiently they are achieving their objectives. Management control systems (MCS) can provide a major input to this type of evaluation and, in addition, can assist in planning, motivating staff, and securing co-ordination at various levels in the organisation. This article examines the use of management control systems in the NHS. PMID- 8452804 TI - Investigating drug induced alopecia. AB - The propensity of cytotoxic drugs to cause alopecia is well known, but nurses are perhaps less aware of the capacity of other drug groups to cause this unwanted side-effect. Increasing nurses' awareness of the actions of these drugs will enable the association between alopecia and toxicity to be recognised at an early stage, before the distressing effects of drug-induced alopecia develop. PMID- 8452806 TI - Sister Susie. Go forth and multi-skill. PMID- 8452805 TI - Communication: mind your language. PMID- 8452807 TI - Professional conduct: crimes (and misdemeanours). PMID- 8452808 TI - Audit, don't applaud it. PMID- 8452809 TI - How to--the Standard guide to using libraries without tears. PMID- 8452810 TI - Assessing a wound (continuing education credit). PMID- 8452811 TI - Simple analgesics: choosing with care (continuing education credit). PMID- 8452812 TI - Mutations of the chloramphenicol acetyl transferase transgene driven by the immunoglobulin promoter and intron enhancer. AB - Transgenic mice containing the chloramphenicol acetyl transferase (CAT) gene driven by the immunoglobulin (Ig) VH promoter and the heavy chain intron enhancer were prepared to increase our understanding of the mechanism responsible for somatic mutation. The transgene showed similar tissue specificity in terms of expression as endogenous Ig genes. Hybridomas were prepared after multiple immunization of a transgenic mouse with (4-hydroxy-3-nitrophenyl)acetyl-chicken gammaglobulin, a thymus-dependent antigen. We analyzed mutations in the CAT coding region as well as in the region 5' upstream of the promoter after amplification of DNA using the PCR followed by sequencing of cloned DNA. Mutation detection enhancement gel electrophoresis was also used to detect mutations. Only a single band was observed in PCR products from the region 5' upstream of the promoter and from the enhancer, whereas in those from the CAT coding region, three out of 11 hybridomas showed multiple bands. In DNA sequences of the CAT coding region from these three hybridomas, a total of six nucleotide substitutions were observed, but none in the region 5' to the promoter. The results of DNA sequencing and the electrophoresis were in good agreement, suggesting that mutation occurred only in the CAT gene but not in the region 5' to the promoter or the enhancer. The rate of mutation in the CAT gene was estimated to be 1.6 x 10(-5) per base pair per cell division, which was a lower limit of the rate for somatic mutation reported for Ig genes. Location and distribution of mutations were similar to that of the Ig gene, suggesting that (i) mutation in the CAT gene was induced by a mechanism similar to that occurring in the Ig gene and (ii) the mutator mechanism can operate in a non-Ig gene provided it is flanked by the VH promoter and heavy chain intron enhancer. PMID- 8452813 TI - Enhanced positive selection of a transgenic TCR by a restriction element that does not permit negative selection. AB - Very little is known about the conformational properties of the MHC molecules that are able to signal positive selection of a given TCR. To try to understand these parameters and to determine whether these requirements are shared with interactions during negative selection and antigen recognition, we have studied selection and antigen recognition of a transgenic TCR (specific for lymphocytic choriomeningitis virus glycoprotein and H-2Db) in the context of two Db mutants, H-2bm13 and H-2bm14. The data showed that the transgenic TCR was not positively selected by the H-2bm14 haplotype but, interestingly, enhanced positive selection was seen in H-2bm13 mice. The transgenic TCR could not be negatively selected in H-2bm13 animals persistently infected with the virus (neonatal virus carrier mice), nor could the transgenic TCR be activated by H-2bm13 infected cells in vivo or in vitro. These experiments show that although a TCR may be selected by a mutant MHC molecule, the corresponding viral antigen cannot be recognized in context of the mutant MHC molecule, as judged by both negative selection and T cell reactivity in vivo and in vitro. The 'enhanced' positive selection occurring in the context of Dbm13 suggests that a different conformation of the MHC molecule is able to select the same TCR and also that various TCR-ligand avidities may permit positive selection. PMID- 8452814 TI - Frequent deletion of the transgene in T cell receptor beta chain transgenic mice. AB - TCR V beta 8.1 transgenic mice were generated using a genomic TCR V beta gene construct under the control of its promoter and enhancer. Among three lines of transgenic mice, one line expressed the transgenic TCR on only approximately 70% of peripheral T cells, while the other two lines expressed it on almost all mature T cells. T cells which lacked expression of the transgenic TCR beta chain expressed endogenous TCR beta chains. The molecular basis underlying the lack of transgene expression in T cells of this line of transgenic mice was investigated. The transgenic TCR- cells were isolated by two methods. First, Thy-1+ V beta 8.1/8.2- cells were purified from peripheral T cells using cell sorting. Second, transgenic TCR- T cell clones were established. In both cases, Southern blotting indicated that V beta 8.1- T cells had deleted the transgenic TCR gene. Thus, deletion of the transgenic TCR can occur in a high proportion of T cells, which allows rearrangement and expression of endogenous TCR beta chains. PMID- 8452815 TI - Bone marrow abnormalities in the non-obese diabetic mouse. AB - Several lines of evidence point to abnormalities of the phenotype, cytokine responses, and function of cells of the myeloid lineage in non-obese diabetic (NOD) mice. In this study we have characterized the phenotype and myeloid progenitor function of NOD bone marrow. Two hematopoietic differentiation antigens, Ly-6C and AA4.1, are expressed abnormally on NOD bone marrow cells. While multilineage erythromyeloid progenitor cells (day 12 CFU-S) are normal in number in NOD mice, more differentiated myeloid progenitors are deficient in their in vitro responses to IL-3, granulocyte/macrophage colony-stimulating factor (GM-CSF), and IL-5. Since the diabetes-predisposing Idd-5 gene of NOD mice maps close to the IL-1 receptor, we tested NOD bone marrow cells for a defect in synergy between IL-1 and IL-3; no defect was found. The defects in myelopoiesis described here may predispose the NOD mouse to autoimmunity by impairing macrophage maturation. PMID- 8452816 TI - The IL-4 induced increase in the frequency of resting murine splenic B cells expressing germline Ig heavy chain gamma 1 transcripts correlates with subsequent switching to IgG1. AB - Cytokine induced germline immunoglobulin heavy chain gene transcription appears to signal commitment to an isotype switch and may be the mechanism by which specific switch regions are targeted as the sites for recombination. In this study, the structure and expression of mouse germline gamma 1 RNAs are described. The 5'-ends of these transcripts are derived from an exon denoted I gamma 1, located upstream of the gamma 1 switch region and initiate at multiple sites over a 200 nucleotide region. Sequence analysis of cDNA and genomic clones reveals that these RNAs, unlike other germline CH transcripts, may encode a novel I gamma 1/C gamma 1 heavy chain protein, of which the N-terminal 27 residues are encoded by I gamma 1. In vitro culture of resting or pre-activated splenic B cells in the presence of lipopolysaccharides and interleukin-4 (IL-4) generates clones that secrete both IgM and IgG1 or either isotype alone. IL-4 increases the frequency of clones secreting both IgM and IgG1 and IgG1 alone, suggesting that commitment to IgG1 secretion may be independent of, or associated with, IgM secretion. PCR analysis of gamma 1 germline transcript expression in clonal B cell cultures or single pre-activated B cells, shows that the IL-4 induced increase in the frequency of cells expressing gamma 1 germline transcripts directly correlates with the increased frequency of cells switching from IgM to IgG1 production. This finding statistically confirms at a clonal level the relationship between cytokine induced germline transcription and isotype switching. PMID- 8452817 TI - Gene structure, chromosomal localization, and protein sequence of mouse CD53 (Cd53): evidence that the transmembrane 4 superfamily arose by gene duplication. AB - CD53 is a pan-leukocyte surface glycoprotein which spans the plasma membrane four times and is a member of the transmembrane 4 superfamily (TM4SF). The protein sequence and gene structure of mouse CD53 (Cd53) were determined by isolation of both genomic and cDNA clones. CD53 is highly conserved in evolution, as mouse Cd53 was 91% identical to rat CD53 and 82% identical to human CD53. The mouse Cd53 gene spanned approximately 9.0 kb of DNA and encoded the 219 amino acid residues of CD53 over seven exons. The Cd53 gene produced a 1.8 kb transcript which was dramatically upregulated after cell activation. The mouse Cd53 gene was mapped to chromosome 3, whereas the locus of another TM4SF member, CD37 (Cd37), was mapped to mouse chromosome 7. Three lines of evidence suggest that the TM4SF arose divergently from an ancestral gene. First, the gene structure of CD53 was strikingly similar to two other members of the TM4SF, CD63 and TAPA-1; second, Cd37 mapped to the same chromosome as Tapa-1; and, third, Cd37 mapped to a segment of chromosome 7 that contains a number of genes that are structurally or functionally related to genes closely linked to Cd53 on chromosome 3. PMID- 8452818 TI - Selection of intestinal intraepithelial lymphocyte T cell receptors: evidence for a dynamic tissue-specific process. AB - An extensive comparison of TCR alpha beta V-region usage by CD8 beta-CD4+CD8+ intraepithelial lymphocytes (IEL), CD4-CD8+ IEL, and lymph node (LN) T cell subsets in three minor lymphocyte stimulating (Mls)-disparate, MHC-identical mouse strains revealed novel TCR selection patterns. In cases where forbidden V regions were expressed by CD8 beta- CD4-CD8+ IEL, the same TCRs were deleted from CD8 beta- CD4+CD8+ IEL, indicating that lack of CD8 beta expression was not solely responsible for forbidden V-region expression. These results also suggested that CD4 may be involved in negative selection of CD4+CD8+ IEL TCRs. In C57BR/cdJ (Mls-1b2b) mice, a major increase in V beta 3+CD4+CD8+ IEL but not in other IEL or LN subsets was noted suggesting a subset-specific expansion of V beta 3+ cells. Negative selection of V beta 14+ cells in only the CD4+CD8+ IEL subset further supported the existence of intestine-specific TCR selection processes. Analysis of V-region expression of CD8 beta + and CD8 beta-CD4-CD8+ IEL subsets revealed that forbidden V-region expression was not strictly confined to the CD8 beta- subset in all cases. Overall, the data point to a dynamic, gut specific TCR selection process that may be antigen driven. PMID- 8452819 TI - B cell development is perturbed in bone marrow from c-fos/v-jun doubly transgenic mice. AB - c-fos and c-jun gene products form a heterodimeric complex (AP-1) that regulates target gene expression by binding to a specific DNA sequence motif. In order to study a role of AP-1 (Fos/Jun) in growth and differentiation of immature B lineage cells, we have established and mated two independent transgenic mice carrying the mouse c-fos gene or the viral v-jun gene fused to the H-2K promoter. IL-7 dependent bone marrow cell culture from doubly transgenic (H2-fos/jun) mice demonstrated severe delay of early B cell development. Proliferation of pre-B cells in the fresh bone marrow from H2-fos/jun mice to IL-7 stimulation was very low. These results suggest that the deregulated production of AP-1 perturbs IL-7 mediated proliferation and differentiation of immature B cells. PMID- 8452821 TI - Does the Journal of Investigative Surgery serve the needs of the surgical research community today? PMID- 8452820 TI - Rag-1: a topoisomerase? AB - Recombination activating genes Rag-1 and Rag-2 were isolated on the basis of their ability to confer V(D)J recombination activity when co-expressed in fibroblasts. The mode of action of the confer V(D)J recombination activity when co-expressed in fibroblasts. The mode of action of the products of these genes is not known. Based on sequence comparison data, it was suggested that Rag-1 protein could act like a topoisomerase and that tyrosine in position 998 could be the active site tyrosine. We tested this hypothesis by introducing a point mutation on the Rag-1 cDNA, transforming the tyrosine codon into a phenylalanine codon. We show that the mutation has no effect on site specific recombination implying that Tyr-998 is not essential for the recombination reaction. PMID- 8452822 TI - A study of the electrical bio-impedance of tumors. AB - A new system of impedance measurement over a frequency range of 0 to 200 kHz was developed by a three-electrode method. In this study, the electrical impedances of various tumors were measured in vivo in 54 patients with breast disease (31 breast cancers, 13 fibroadenomas, and 10 fibrocystic diseases) and 57 patients with pulmonary disease (44 lung cancers, 5 metastatic pulmonary tumors, 4 pulmonary tuberculoses, and 4 organized pneumonias). On the basis of those impedance measurements and the equivalent circuits in vivo, we calculated the extracellular resistance (Re), intracellular fluid resistance (Ri), and cell membrane capacitance (Cm) in tissues, all of which were compared among the various diseases. It was found that Re and Ri were significantly higher in breast cancers than in benign tumors and normal breast tissues and that Cm was significantly lower in breast cancers than in other tissues. On the other hand, Re and Ri were significantly higher, and Cm was significantly lower, in normal lung tissues than in pulmonary masses. Re and Ri were significantly higher, and Cm was significantly lower, in malignant tumors than in organized pneumonias. The results showed that these parameters (Re, Ri, and Cm) exhibit significant differences among various tissues and tumors, suggesting possible applications in tumor diagnosis. PMID- 8452823 TI - Healing after arterial dilatation with radiofrequency thermal and nonthermal balloon angioplasty systems. AB - Thermal balloon angioplasty has been proposed as a means of reducing acute and delayed reclosure of arteries after percutaneous transluminal balloon angioplasty. A radiofrequency (rf) balloon catheter was used to perform thermal balloon angioplasty on canine arteries in vivo. The histologic appearance of rf treated sites was compared with that of control sites treated by conventional percutaneous transluminal angioplasty. Acutely, rf-treated sites showed a reduced medial cellularity with preservation of internal elastic lamina except at the transitional zone between thermal injury and normal artery, where localized internal elastic lamina disruption was found. Nonthermal sites showed generalized disruption of internal elastic lamina and normal medial cellularity. Both thermal and nonthermal sites displayed a return of intimal cover commencing at 1 to 2 weeks and completed by 4 weeks. Diffuse myointimal hyperplasia appeared by 2 weeks after injury at breaks in the internal elastic lamina along the nonthermal vessels but was localized to the transitional zone in thermal injury sites. In rf treated vessels, repopulation of the acellular thermally modified media had commenced by 4 weeks, and by 8 weeks the media was diffusely repopulated by spindle-shaped cells resembling smooth muscle cells lying between and aligned with preserved connective tissue laminae. Overall, the distribution and extent of the proliferative response after rf thermal balloon angioplasty were less than those seen after nonthermal balloon angioplasty. Thermal sites, which underwent reintimalization before medial cells returned, were considerably less prone to the development of myointimal hyperplasia. These results suggest that this modality may have beneficial effects on arterial healing after angioplasty. PMID- 8452824 TI - A canine iliac artery occlusion model. AB - This report describes an occlusive canine iliac artery model for use in experimental angioplasty procedures. Lesions were induced by overdistending and breaking the internal elastic lamina of the artery and implanting a 2-cm long occlusive collagen plug. The collagen plug diameter was varied to fit the iliac artery and caused immediate bilateral iliac occlusions. Histology of the lesions at 9 and 14 days (n = 2) showed that the lumen was filled with a mixture of fresh thrombus and collagen pad material (more collagen than thrombus) with focal disruptions of the internal elastic lamina. At 36 days (n = 2) the lumen was obliterated with a mixture of organizing thrombus and collagen pad material (more organizing thrombus than collagen). At 60 (n = 4) and 80 (n = 8) days the collagen pad had been completely replaced with organizing thrombus consisting of collagen fibers and hemosiderin-laden macrophages with persistent focal disruptions of the internal elastic lamina. These initial data demonstrate the ability to create fibrotic arterial occlusions in as short a time as 60 days and to provide a practical model to study methods for treating localized peripheral vascular occlusive disease. PMID- 8452825 TI - The effect of interstitial hyperthermia on local pulmonary blood flow and lung parenchyma. AB - Hyperthermia has shown promise as an anticancer therapy, but its application to lung neoplasms has been limited by whole body hyperthermia complications and the intrathoracic location of lung neoplasms. Previous studies have shown that interstitial hyperthermia could be performed through a thoracotomy approach and that animals tolerated the procedure without biochemical or hematologic abnormalities. The normal lung's local blood flow pattern and parenchymal changes due to hyperthermia of various temperatures and durations were studied. The experimental protocol applied hyperthermia through interstitial electrodes at temperatures of 39 degrees, 41 degrees, 43 degrees, and 45 degrees C. Tissue blood flow was measured with radioactive microspheres at 20, 40, and 60 minutes of hyperthermia. Histologic examination was performed of biopsy specimens taken from the heated area, from 2 and 5 cm from the heated area, and from distant parenchyma. These initial studies demonstrate that interstitial hyperthermia in the normal lung does not cause a decrease in pulmonary vascular resistance, that interstitial hyperthermia in the normal lung at temperatures of 43 degrees or 45 degrees C for durations of longer than 20 minutes decreases local pulmonary blood flow, that interstitial hyperthermia causes mild vascular disruption at temperatures of 39 degrees C or greater in the heated area but does not affect adjacent or distant lung parenchyma, and that lung hyperthermia causes generalized vascular disruption with severe widening of the pulmonary interstitium and severe hemorrhage in the heated areas when temperatures of 43 degrees or 45 degrees C are applied. Because interstitial hyperthermia affected only local lung damage, it may be applicable in the treatment of localized lung tumors. PMID- 8452826 TI - Comparison of preoperative standard angiography with preoperative balloon occlusion femoral angiography of the lower extremity. AB - The use of saphenous vein in situ bypass for limb salvage has increased the need for adequate visualization of distal lower extremity vessels. Preoperative angiographic techniques are often inadequate, requiring multiple films, extensive patient manipulation, or excessive dye loads. Intraoperative prereconstructive angiography permits adequate distal vessel visualization, but at a significant waste of time and expense if no usable distal vessels are found. There is a need for a reliable means of preoperative angiography in patients being evaluated for saphenous vein in situ bypass. Preoperative balloon occlusion femoral angiography was compared to preoperative standard angiography of the lower extremity in 39 patients referred to the University of Minnesota for limb salvage. Balloon occlusion femoral angiography significantly improved the preoperative ability to visualize lower extremity vessels distal to the superficial femoral artery in this group of patients. PMID- 8452827 TI - Function of peritoneal exudate cells after abdominal surgery. AB - Peritoneal macrophages and polymorphonuclear neutrophils are key cells in the repair of postoperative injury. Increased numbers of macrophages migrate into the peritoneal cavity after operation and the function of these cells changes over the postoperative interval. Macrophage activities, such as respiratory burst, arachidonic acid metabolism, monokine secretion, and plasminogen activator inhibitory activity, are elevated by peritoneal operation. However, the secretion of plasminogen activator activity is decreased after operation. The kinetics with which each of these functions changes varies with the parameter examined, indicating a complex regulation of the differentiation of leukocytes after operation. In addition, the activity of postoperative macrophages can be modulated in vitro by exposure to cytokines and conditioned media from polymorphonuclear neutrophils and macrophages. Thus, cell-cell interactions and factors secreted within the peritoneal cavity may regulate the contribution of postoperative leukocytes to peritoneal repair after operation. PMID- 8452828 TI - Transurethral canine prostatectomy with the Nd:YAG laser. AB - Although laser energy in combination with conventional techniques has been used to ablate prostatic tissue in the dog, the use of the Nd:YAG laser alone to perform transurethral prostatectomies has not been feasible because of the difficulty of directing the laser energy into the prostate. In this study, a 600 microns quartz laser fiber with an attached gold-plated metal alloy reflector and a 1.06-microns Nd:YAG laser were used to perform transurethral laser prostatectomies in 10 mongrel dogs. Each dog received approximately 3600 J to each quadrant of the prostate. No signs of urinary incontinence were noted in any of the dogs postoperatively. Transurethral laser prostatectomies can be performed safely and effectively in the dog and can significantly decrease the incidence of postoperative urinary incontinence. PMID- 8452829 TI - Data analysis in craniofacial biology with special emphasis on longitudinal studies. AB - Recommendations are made for strengthening data description and analysis in craniofacial biology. Special emphasis is placed on longitudinal data, and PC programs for accomplishing appropriate analyses in this context are described and made available to interested readers. Some more general recommendations are treated in less detail. These include the effective description of data using stem-and-leaf displays and/or boxplots, the use of decision-analytic methods in the management of patients with dentofacial deformities, and the valid application of certain statistical methods in single-subject studies. Finally, it is conjectured that computer-intensive methods such as randomization tests and jackknifing will play an increasingly prominent role in craniofacial research. PMID- 8452830 TI - Congenital bilateral coronal suture synostosis in a rabbit and craniofacial growth comparisons with experimental models. AB - Experimental rabbit models of postnatal coronal suture (CS) synostosis have helped make significant contributions towards the understanding and surgical management of human congenital craniosynostosis. The present study compares craniofacial growth patterns in animals with experimental CS immobilization and in a rabbit born in our laboratory with congenital CS synostosis. The study sample consisted of 10 sham controls, 14 experimental animals with bilateral CS immobilization, and one animal with congenital, bilateral CS synostosis. At 1.5 weeks of age, all animals had amalgam markers placed on either side of the frontonasal, coronal, and anterior lambdoid sutures. At this time, the experimental animals had bilateral CS immobilization using methyl-methacrylate. Serial lateral head x-rays were taken at 1.5, 6, 12, and 18 weeks of age. Results revealed that by 1.5 weeks of age the congenital animal already exhibited changes in the cranial vault, cranial base, midface, and orthocephalic cranial base angles compared to controls. By 6 weeks of age, animals with experimental immobilization showed compensatory growth patterns similar to the congenital animal, particularly at the calvarial sutures and upper midface. This pattern continued through 18 weeks. Results showed that experimental, postnatal CS immobilization produced similar craniofacial growth patterns to those observed for our single congenital animal, but to a lesser degree, and therefore validates, in part, findings from experimental rabbit models of synostosis. PMID- 8452831 TI - Maxillary arch dimensions after palatal surgery and implantation of poly-(L lactic) acid membranes in beagle dogs. AB - The effect of implantation of poly-(L-lactic) acid membranes after palatal surgery on dentoalveolar development was investigated. Beagle dogs were randomly assigned to four experimental groups and a control group. In the experimental groups, a soft tissue defect was created in the medial region of the palate by excising a standardized elliptical mucoperiosteal flap at 12 weeks of age. This defect was closed according to the Von Langenbeck technique, leaving two areas of denuded bone. Poly-(L-lactic) acid membranes were implanted on the denuded bony areas either directly or 3 weeks after surgery. Group L and LS served as sham groups. Dental casts were made at regular intervals until 25 weeks of age, and maxillary arch dimensions were studied. Dental arch dimensions in the deciduous dentition of the experimental groups were not markedly disturbed, but after transition of teeth, mainly transversal maxillary arch dimensions in the premolar region were reduced. It was concluded that implantation of poly-(L-lactic) acid membranes after palatal surgery in Beagle dogs did not prevent iatrogenic disturbances of dentoalveolar development under conditions used in this study. PMID- 8452832 TI - NORAM--an instrument used in the assessment of hypernasality: a clinical investigation. AB - The speech of 102 patients with complete unilateral and bilateral cleft lip and palate and 40 noncleft subjects was analysed using the NORAM (Nasal Oral Ratio Meter) instrument. The results obtained were compared with the perceptual judgments made by experienced listeners. A significant correlation was found between the NORAM values and the listener judgments. The NORAM instrument can thus be used as a complement to listener judgments in assessing hypernasality. A discussion of the acoustic and phonetic aspects of the differences between the instrumental and perceptual results is presented. PMID- 8452833 TI - Velopharyngeal sphincter physiology in deaf individuals. AB - Fifty-three deaf subjects with a history of prelingual profound bilateral sensorineural hearing loss, similar language habilitation with hearing aids, and normal velopharyngeal structures underwent a study protocol including speech evaluation, behavioral pure-tone audiometry, videonasopharyngoscopy, multiview videofluoroscopy, and electromyography of the velopharyngeal muscles. Subjects were divided into two groups: the first group included 13 subjects with normal nasal resonance or mild hypernasality (four normals and nine with mild hypernasality); the second group had subjects with severe hypernasality and severe articulation deficits. Pure-tone thresholds, velopharyngeal closure patterns, and electromyographic activity of velopharyngeal muscles were similar for both groups of subjects. However, in subjects with severe hypernasality, despite normal muscle activity as observed by electromyography, velopharyngeal valving activity lacked rhythm and strength during speech. It is concluded that deaf subjects may present a functional disorder of the velopharyngeal sphincter related to absence of auditory regulation during phonation. Visual biofeedback using videonasopharyngoscopy may be useful for treating this disorder. PMID- 8452834 TI - Interactive influence of a pharyngeal flap and an adenoid on maxillofacial growth in cleft lip and palate patients. AB - The aim was to evaluate whether a large adenoid, which aids velopharyngeal function, influences facial growth and if a pharyngeal flap reinforces the effect. Forty cleft palate patients were divided into two groups: adenoid and nonadenoid. Twenty of the patients had a pharyngeal flap operation. All the patients had three cephalograms taken at the same ages over a period of 5 years. At an average age of 4.7 years, i.e., one year before any pharyngoplasty, the mandibular inclination was larger in the adenoid group. This inferioposterior mandibular position was aggravated when a flap was added and with age. The present study suggests that the nasopharyngeal space, which is indicative of nasal airway patency, is influenced by a pharyngeal flap as well as an adenoid which, in turn, influences facial growth direction in the cleft palate population. Airway variables ought to be taken into consideration when the growth effect of cleft palate treatment is evaluated. PMID- 8452835 TI - Hypernasality in the presence of "adequate" velopharyngeal closure. AB - In some instances, hypernasality occurs despite an instrumental assessment of "adequate" velopharyngeal closure. The pressure-flow technique was used to assess the timing characteristics associated with velopharyngeal closure in 11 such subjects. The group's performance was compared to the aerodynamic characteristics of two other subject groups. One was comprised of 13 cleft palate subjects with adequate closure and normal nasal resonance, while the second group consisted of 16 noncleft subjects who also manifested normal speech. The data indicate that there are several unique timing features that differentiate the hypernasal but "adequate" group from the two control groups. These include a delay of about 50 ms in achieving closure, a longer interval of nasal emission, and a shorter duration of actual closure. Hypernasality seems to be associated with the actual time the velopharyngeal mechanism is open, rather than the volume of air escaping from the nasal chamber. PMID- 8452836 TI - Maxillary arch analysis: utilizing a computer-based method. AB - Objective, computerized analysis of the maxillary arch was used for morphologic studies of cleft palate characteristics. A method for maxillary arch analysis was developed and used in 10 randomly selected, cleft palate patients. The computerized analysis procedure is described in detail. PMID- 8452837 TI - Growth of costochondral fragments transplanted from mature to young isogeneic rats. AB - Experiments were carried out to determine whether growth of costochondral grafts is associated with age-related humoral factors. Rib fragments containing either short (without germinative zone) or long (with proliferative and germinative zones) cartilaginous ends were excised from adult rats, and the sections transplanted across the interparietal suture in 10-day-old isogeneic rats. The animals with short cartilage transplants were killed 15 or 25 days later; those with long cartilage transplants 25 days postoperatively. Measurements on dry skulls with short transplants showed neurocranial width to be greater in the experimental rats than in the unoperated controls at 25 days, whereas 10 days later the difference was no longer significant. By the latter time, however, the neurocranium was significantly wider in the long cartilage group than in the other groups. It is suggested that the declining growth potential of the costal cartilages from the adult rats was reactivated when transplanted to younger animals, i.e., the growth of costochondral transplants is related to humoral factors. PMID- 8452838 TI - Experimental effects of bone plating in infancy on craniomaxillofacial skeletal growth. AB - The potential effects of mini- and microfixation on craniofacial development was investigated in an animal model. Twenty-four rabbits had amalgam markers placed bilaterally at the lambdoid, coronal, and frontonasal sutures at 28 days of age. In group 1, plating was not done and served as controls. In groups 2 to 4, single 2- and 4-hole microplates and 4-hole miniplates were fixed across the left coronal suture. The right suture was not plated. After 6 months, intermarker distances and craniofacial angles were measured radiographically. Coronal sutures underneath the plates were also histologically evaluated. Plating across the coronal suture resulted in local anteroposterior constriction of marker distances that did not differ with the type of fixation used. More distant markers, however, were increased in all specimens as a compensation and, as a result, the cranionasal length of all groups were similar. No change in craniofacial angles was observed from that of the controls. Sutural morphology on the side of fixation was altered with decreased widths, cellular numbers, and bone deposition. These experimental results demonstrate that early plate application in a normal calvarium results in local growth restriction that can be overcome by regional bone growth compensation. PMID- 8452839 TI - Size and form of the cranial base in isolated cleft lip and palate. AB - Most cases with cleft lip and palate (CLP) have no other obvious malformation and are termed isolated CLP. The implication is that these individuals experienced a time-specific and anatomically-localized disturbance during palatogenesis but are otherwise normal. The cranial base was studied from cephalograms in subadults with isolated CLP (n = 43) to test for alterations in size and shape. Controlling for age and gender, analyses showed no size difference, but flexure of the cranial base was significantly greater in the CLP group. Taken in conjunction with increased risks of other conditions with prenatal onsets, it appears that "isolated CLP" is a misnomer and the cleft should be viewed as an overt manifestation of a more generalized growth disturbance. PMID- 8452840 TI - Relationship between cleft severity and dentocraniofacial morphology in Japanese subjects with isolated cleft palate and complete unilateral cleft lip and palate. AB - Relationships between the width of the palatal cleft measured at palatoplasty and the craniofacial morphology or the occlusal conditions present at approximately 4 years of age were studied in 25 cleft palate (CP) and 39 complete unilateral cleft lip and palate (UCLP) subjects treated at the Dental Clinic of Kyushu University. Posteroanterior cephalograms and dental casts showed that the width of the palatal cleft was significantly correlated with wider upper facial width and posterior dental arch width in UCLP, but not in CP subjects. Cleft width was not significantly correlated with the buccolingual occlusal relationship in either subject type. The anterior occlusal relationship in UCLP was not as good as in CP subjects. On lateral cephalograms, the width of the palatal cleft was significantly correlated with vertical hypoplasia of the upper face in UCLP, but not in CP subjects. The cleft palate width appears to be related to the lateral displacement and the retardation of the downward and forward growth of the nasomaxillary complex in UCLP subjects. PMID- 8452841 TI - Orthopedic protraction of the upper jaw in cleft lip and palate patients during the deciduous and mixed dentition periods in comparison with normal growth and development. AB - Cleft lip and palate (CLP) patients often develop maxillary retrusion after cleft repair. Since 1977, a group of 98 cases with negative overjet (anterior crossbite) during the period of deciduous dentition has been treated by the Bergen CLP team. The purpose of treatment has been to achieve favorable occlusion with positive overjet and overbite by means of anterior orthopedic traction (protraction). The average age at start of treatment was 6 years 11 months, and mean treatment duration was 13 months. The protraction force was 700 g. The serial lateral cephalograms of the treated CLP group were compared with those of a noncleft group with normal growth. Normalization of the sagittal maxillomandibular relationship (ANB angle) was achieved. Significant changes were a more anterior position of the upper jaw, and a more posterior position of the lower jaw, due to mandibular clockwise rotation. The variation was considerable. This paper reports the overall changes in the whole CLP group (ALL-C group). PMID- 8452842 TI - Intercanine widening and sagittal effect of maxillary transverse expansion in patients with cleft lip and palate during the deciduous and mixed dentitions. AB - Since 1977 cleft lip and palate (CLP) patients with maxillary deficiency have received an interceptive orthopedic treatment consisting of (a) transverse expansion, (b) protraction, and (c) fixed retention. Ideally the treatment should be completed early enough to permit spontaneous eruption of the maxillary permanent incisors into normal occlusion without orthodontic intervention. The early transverse expansion considerably increases space so that unerupted malpositioned incisors spread out spontaneously, creating optimal conditions for eruption and root formation. Dental diagnosis in the cleft areas is made easier. Posterior crossbites in 112 CLP patients were expanded with a modified quad-helix appliance cemented with four bands in the deciduous or mixed dentition. Intercanine widening was about 3 mm per month regardless of cleft type. Several authors have claimed that transverse expansion of the upper jaw will increase sagittal overjet. Other authors have not found such an effect. The sagittal effect on the maxilla was studied in 68 CLP patients who had received transverse expansion. Analysis of the lateral cephalograms revealed no significant sagittal dentofacial maxillary treatment effects involving forward movement of maxilla, but a downward clockwise rotation of the mandible was found. PMID- 8452843 TI - Maxillary protraction: different effects on facial morphology in unilateral and bilateral cleft lip and palate patients. AB - Since 1977 patients with anterior/posterior crossbites in the care of the Bergen CLP team have undergone an interceptive orthopedic protraction phase during the deciduous and mixed dentition period. Eighty-seven cases with complete clefts (63 unilateral and 24 bilateral) displaying anterior crossbite (negative overjet) were treated to normal occlusion. A fixed quad-helix appliance was used in combination with a facial mask. In the unilateral complete cleft lip and palate (UCLP) group, mean age at start of treatment was 6 years 10 months and mean duration was 12 months. In the bilateral complete cleft lip and palate (BCLP) group, mean age at start of treatment was 7 years and mean duration 15 months. The protraction force was 700 g. The sagittal changes during protraction in the UCLP and BCLP groups were compared, and related to the growth changes in a group of noncleft children at the same age. Dentofacial treatment effect was different in the UCLP and BCLP groups. Significant increase of maxillary prognathism (angle s-n-ss) was found only in the UCLP group, whereas the treatment effect in the BCLP group was mainly dentoalveolar. However, after protraction there was no longer a significant difference in maxillary prognathism between the two CLP groups, and the sagittal position of the upper molars was normalized in both groups. The upper incisors remained retroclined in both groups, significantly more in the BCLP group. Increase of the upper facial height (n-sp") and clockwise rotation of the occlusal line were significantly greater in the BCLP group. The computerized occlusal line was unsuitable as a reference standard for the evaluation of sagittal dentofacial treatment changes when the occlusal line was rotated during treatment. PMID- 8452844 TI - Nasal septal deformity in unilateral cleft lip and palate. AB - The present study is part of a larger rhinomanometric investigation to determine the type and extent of nasal septal deformity in subjects with repaired unilateral complete clefts of the lip and palate (UCLP). The cleft sample consisted of 21 subjects (mean age 16.4 years). A control group consisted of 30 subjects (mean age 13.1 years). The rhinomanometric measurements in this study have been previously reported (Sandham and Solow, 1987) and showed that bilateral nasal resistance did not differ significantly between the cleft sample and the controls. Unilateral measurements of nasal resistance showed higher valves for the cleft side than the noncleft side (p < .001). Nasal septal deformity was scored for anomaly type and severity, by direct visual observation of each nasal compartment. The results showed that nasal septal deviation occurs more frequently in subjects with cleft lip and palate than controls (p < .001). The cartilaginous nasal tip, like the maxillary nasal spine, deviated to the noncleft side because of its dependency for directional control on the maxillary crest, and it projected into the nasal aperture of the noncleft side. The most frequent deviation of the bony septum was to the cleft side, and this not only involved the valve area but also a broader area opposite the turbinates. PMID- 8452845 TI - Sri Lankan cleft lip and palate study model analysis: clefts of the secondary palate. AB - The study models of a group of adult Sri Lankan patients with clefts of the secondary palate were investigated. Tooth-size and arch-dimension comparisons were made with a comparable control group. Significant differences were found between the cleft and control groups in tooth sizes, chord lengths, and arch widths. The cleft group dimensions were generally smaller than those of the control group. Overjets were larger in the cleft group. PMID- 8452846 TI - Primary correction of the unilateral cleft lip nose. AB - The details of surgical techniques for primary correction of the unilateral cleft lip nose and their results for 45 cases are reported. The technique employed an infracartilaginous incision on the affected side, thus allowing direct suturing of the alar cartilage onto the lateral cartilage. For the post-operative evaluation, the nasal form in both frontal and bottom views was scored for five items. In overall evaluation, the grades of "Good," "Fair," and "Poor" were derived from the total scores of five items. In the postoperative results (range of follow-up: 24 months to 84 months), 24 cases were rated "Good" (53.3%), 13 cases "Fair" (28.9%), and 8 cases "Poor" (17.8%). Thirty cases appear not to need secondary correction (66.6%). The technique is useful because the alar cartilages and lateral cartilages can be accurately sutured, and relatively stable results can be obtained. PMID- 8452847 TI - Long-term results after maxillary advancement in patients with clefts. AB - In order to evaluate relapse tendencies after maxillary advancement, 31 patients were examined preoperatively, postoperatively, and 1 year postoperatively; 14 of whom had clefts of the lip, alveolus, and palate. Patients with maxillary deficiency were selected in a method that mere sagittal displacement was planned. Any patients with major vertical or transverse changes or additional mandibular surgery were excluded. Treatment consisted of maxillary advancement by Le Fort I osteotomy and miniplate fixation. Besides clinical examination, skeletal and dental changes were assessed cephalometrically. Results revealed a certain relapse tendency of the displacement in the noncleft group that compared favorably to the cleft group. This relapse is dependent on the amount of advancement. Despite minor differences, the two groups did not differ significantly based on maxillary advancement, so besides advancement surgery there must be another factor, cleft, to explain the different relapse tendencies between patients with and without clefts. PMID- 8452848 TI - Masticatory function in a patient with mandibular midline cleft. AB - Bone grafting of a midline cleft is required to allow reasonable masticatory function. However, changes in the rhythm of mastication have not been investigated before and after such bone grafting procedures. We performed bone grafting in a patient with multiple craniofacial anomalies including a midline mandibular cleft. The patient showed a marked improvement in the rhythm of mastication after repair of the midline mandibular defect. Bone grafting proved to be an effective method for securing stable occlusion with better mandibular movement. PMID- 8452849 TI - Taking dental impressions in infants with cleft lip and palate. PMID- 8452850 TI - A six-center international study of treatment outcome in patients with clefts of the lip and palate: evaluation of maxillary asymmetry (Cleft Palate Craniofac J 1993; 30:22-28). PMID- 8452851 TI - Incidence of cleft lip and palate in a newborn Zairian sample. PMID- 8452852 TI - Craniofacial skeletal measurements based on computed tomography. PMID- 8452853 TI - Molecular mechanism of the lipid vesicle longevity in vivo. AB - An important, if not the chief, condition for the prolongation of the circulation times of lipid vesicles in vivo is the suppression of macromolecular adsorption onto the surface of such vesicles. This adsorption can be prevented very efficiently by a zone of suitably designed and mobile steric hindrances near the lipid layer surface. Lipid vesicles with such a surface coat, cryptosomes, thus circulate in blood for very long periods of time after systemic applications. Lipid vesicles composed of phosphatidylcholine molecules and of suitable polyoxyethylene (PEG) derivatives of phosphatidylethanolamine, for example, remain in the blood circulation 8-10-times longer than standard liposomes made of phosphatidylcholine only: in mice the half-lives of the former and latter vesicles, after an i.v. administration, are approx. 0.6 h and between 5.9 and 13.8 h, respectively. Vesicle longevity is not destroyed by the phosphatidylcholine chains fluidity. Vesicles consisting of a mixture of distearoylphosphatidylethanolamine-PEG (DSPE-PEG) with distearoylphosphatidylcholine or cryptosomes made of DSPE-PEG and soy-bean phosphatidylcholine, consequently, have a very similar fate in vivo. Furthermore, the cryptosome longevity is not affected directly by the presence of the net charges on the lipid membranes and is little sensitive to the details of the group coupling the PEG-headgroups and the lipidic (hydrophobic) anchor. However, the life-time and the distribution of the stabilized lipid vesicles in vivo depend quite sensitively on the surface density of the sterically active headgroups; often (if not always) the resistance to plasma components adsorption as well as the resulting longevity in vivo both show a maximum near the same lipid/stabilizer molar ratio. Optimum bilayer composition may differ for the different combinations of the main and sterically active membrane components. Its position is probably determined by the variations in the molecular mobility and the effective surface-coverage effects: both must be sufficiently high for the vesicle phagocytosis and accumulation in the reticulohystiocytic system to be suppressed. On the contrary, the bilayer surface hydrophilicity, which hitherto has been believed to be of paramount importance for the liposome longevity in vivo, is per se not relevant for the biological fate of the lipid vesicles, provided that this hydrophilicity exceeds some minimum value. PMID- 8452854 TI - A nucleotide-regulated Cl-/OH- anion exchanger in endoplasmic reticulum-enriched pig pancreatic microsomes. AB - The anion conductive pathways in preparations of endoplasmic reticulum (ER) enriched microsomes from pig pancreas were investigated. The rate of swelling induced by cation ionophores (nigericin (nig) and/or valinomycin (val)) was measured in iso-osmotic solutions by light scattering, in the presence or absence of an inward Cl- and/or pH gradients. The rate of swelling in the presence of the inward Cl- gradient and ionophores was faster than that of controls. Low pH did not change the swelling rate in the presence of valinomycin, but it increased it in the presence of nigericin. When the Cl- gradient was abolished, valinomycin plus the pH gradient increased the rate of swelling, and this was further enhanced by nigericin. Anion transport inhibitors reduced the swelling rate. The nigericin-induced swelling was stimulated by ATP and GTP. The non-hydrolysable analogues, adenosine 5'-[beta,gamma-methylene]triphosphate, guanosine 5'-[beta thio]triphosphate and guanosine 5'-[beta-thio]diphosphate, increased the rate of swelling, whereas adenosine 5'-[gamma-thio]triphosphate inhibited it. ADP, CTP and UTP had no effect. These data suggest the presence of a Cl-/OH- exchanger and a Cl- conductance in microsomes. They indicate that nucleotides may regulate the Cl-/OH- exchanger. Nucleotides do not need to be hydrolyzed but phosphorylation may occur to counter-balance the nucleotide-induced stimulation. PMID- 8452855 TI - Characteristics of organic cation transporter in rat renal basolateral membrane. AB - Characteristics of organic cation transport system were studied in rat renal basolateral membrane and compared with those in brush-border membrane. We first examined the effect of various chemical modifiers on tetraethylammonium uptake by the membrane vesicles. Treatment with N,N'-dicyclohexylcarbodiimide and phenylglyoxal (carboxyl groups and arginine residues specific reagent, respectively) resulted in inhibition of tetraethylammonium transport in both basolateral and brush-border membranes. Tetraethylammonium uptake by brush border, but not by basolateral, membrane vesicles was decreased by diethyl pyrocarbonate, histidine residues specific reagent, treatment. Treatment of sulfhydryl groups with HgCl2 decreased tetraethylammonium transport in both membranes. However, in contrast to brush-border membrane, unlabeled tetraethylammonium failed to protect against the inhibition of [14C]tetraethylammonium uptake by p-chloromercuribenzene sulfonate in basolateral membrane. We next examined the inhibitory effect of various organic cations on tetraethylammonium uptake. The order of inhibitory potency of organic cations was somewhat different between two membranes. These findings suggest that the characteristics of organic cation transport systems in basolateral and brush border membranes were different in regard to essential amino acid residues and the affinity of substrates. PMID- 8452856 TI - The expression of the Na+/glucose cotransporter (SGLT1) gene in lamb small intestine during postnatal development. AB - We have shown previously that the activity and abundance of the intestinal Na+/glucose cotransporter (SGLT1) declines dramatically during the postnatal development of lambs, and that it can be restored in the intestine of ruminant sheep by intra-luminal infusion of D-glucose. The work presented in this paper has followed the expression of the SGLT1 gene along the vertical and horizontal axes of the ovine small intestine during early development, using quantitative in situ hybridisation histochemistry. Along the vertical axis, SGLT1 mRNA was first detectable just below the crypt-villus junction and rose rapidly to a peak level approx. 150 microns above this point. After reaching a maximum, the amount of message gradually declined towards the villus tip. This pattern of mRNA accumulation along the crypt-villus axis was similar in all intestinal positions and age groups. Along the length of the small intestine (horizontal axis), a decline in the level of SGLT1 mRNA was observed first in the distal intestine. This decrease in SGLT1 mRNA was significant in the intestine (75% of length) of 5 week-old lambs when compared to tissue taken from 25 and 50% of length (P < 0.01 and P < 0.02, respectively). However, the observed fall in the expression of this gene during weaning did not coincide with the fall in activity and amount of SGLT1. In adult animals, where the activity of SGLT1 is very low, the amount of message was greatly reduced. This work supports the finding that the expression of SGLT1 is primarily controlled at the post-transcriptional level during the postnatal development of ovine intestine. PMID- 8452857 TI - Folding and dynamics of melittin in reversed micelles. AB - The main structural characteristics and the dynamic properties of melittin bound to the internal surface of reversed micelles, formed by sodium bis(2-ethyl-1 exyl)sulfosuccinate (AOT) in isooctane, were investigated by several spectroscopic techniques. Melittin has been found associated to reversed AOT micelles in a single state, thus indicating that this system behaves differently with respect to phospholipid vesicles where at least two forms of lipid associated melittin are observed. The dynamic properties of melittin in reversed AOT micelles at different water contents were examined by frequency domain fluorometry. The whole emission decay was analyzed in terms of lifetime distribution having a Lorentzian shape. The results indicated that the binding of melittin to inverted micelles determines an increase of emission heterogeneity compared to that observed for the fully extended helical monomer. This was explained in terms of a larger variety of microenvironmental conditions that the tryptophan residue experiences during its excited state. However, the conformation freedom of the peptide can be modulated by varying the micellar size. PMID- 8452858 TI - Influence of lipid lateral distribution on the surface charge response of the phosphatidylcholine headgroup as detected using 2H nuclear magnetic resonance. AB - The effect of lipid lateral distribution on the surface charge response of the phosphatidylcholine headgroup, in bilayers composed of binary mixtures of 1 palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1,2-dimyristoyl-sn glycero-3-phosphate (DMPA), was investigated by monitoring the deuterium nuclear magnetic resonance (2H-NMR) spectrum of choline-deuterated phosphatidylcholine as a function of temperature and DMPA concentration. Addition of DMPA at temperatures corresponding to fully liquid-crystalline membranes caused a progressive increase (decrease) in the 2H-NMR quadrupole splitting from POPC alpha-d2 (POPC-beta-d2), in agreement with the known response of phosphatidylcholine to negative membrane surface charge (Seelig, J., Macdonald, P.M. and Scherer, P.G. (1987) Biochemistry 26, 7535-7541). Lateral phase separation of DMPA-rich domains was induced in these mixtures by lowering the temperature in the range from 60 degrees C to -15 degrees C, and was accompanied by a reversal of the original effects of DMPA on the quadrupole splitting. Analysis of the 2H-NMR spectral response allows one to generate a temperature/composition phase diagram for the POPC/DMPA system. We conclude that 2H-NMR of headgroup-deuterated phosphatidylcholine can be employed to sense and to quantify inhomogeneities in the lateral distribution of charged membrane components. PMID- 8452859 TI - Curvature dependent induction of the interdigitated gel phase in DPPC vesicles. AB - Ethanol causes biphasic melting behavior in saturated lecithins (Rowe (1983) Biochemistry 22, 3299-3305), a consequence of the formation of the stable interdigitated phase (Simon, S.A. and McIntosh, T.J. (1984) Biochim. Biophys. Acta 773, 169-172). The membrane systems studied to date have been large vesicle systems in which the membrane surface can be assumed to be locally planar. An immediate question arises as to whether surfaces of higher curvature interdigitate. To address this question we have prepared DPPC vesicles of varying diameters which we employed to determine the limiting size at which interdigitation occurs using ethanol as the inducer. We find that with decreasing vesicle size the concentration of ethanol necessary for the onset of interdigitation increases. Small isolated vesicles, at inducing concentrations of ethanol, do not stably interdigitate but rupture and coalesce into a viscous gel comprised of interdigitated lipid sheets. As discussed elsewhere (Ahl et al. (1992) Biophys. J. 243a) these sheets can be used as precursors for producing liposomes of large size and high internal volumes useful in drug delivery or modeling applications. PMID- 8452860 TI - Cryotoxicity of antifreeze proteins and glycoproteins to spinach thylakoid membranes--comparison with cryotoxic sugar acids. AB - We have used thylakoids from spinach (Spinacia oleracea L.) chloroplasts to test the effects of antifreeze proteins (AFP) from the starry flounder (Platichthys stellatus; AFP-SF) and from the antarctic eel pout (Austrolycichthys brachycephalus; AFP-AB), and antifreeze glycoproteins (AFGP) from the antarctic fish Dissostichus mawsoni on biological membranes during freezing. Freeze-thaw damage, measured as the release of the lumenal protein plastocyanin from the thylakoid vesicles, was strongly increased in the presence of all proteins tested. Measurements of the time dependence of plastocyanin release in a simplified artificial chloroplast stroma medium showed that all the fish proteins increased damage during the initial rapid phase while only AFGP increased plastocyanin release during the linearly time dependent slow phase. A slow plastocyanin release is also seen in the absence of freezing. It is increased by the presence of AFGP and AFP-AB, but not by AFP-SF. In order to distinguish between the contribution of the polypeptide and the carbohydrate part of AFGP on freeze-thaw damage we investigated the effects of galactose and N acetylgalactosamine. While galactose was protective, N-acetylgalactosamine increased the rate of plastocyanin release in an artificial stroma medium at -20 degrees C. It had no effect on the rapid phase of damage and was also ineffective at 0 degree C. The same was found for several other sugar derivatives (N acetylglucosamine, gluconic acid, glucuronic acid, galacturonic acid). From these data we conclude that the increased plastocyanin release during the rapid phase of freeze-thaw damage is a function of the polypeptide part of AFGP. The increased rate of plastocyanin loss at longer incubation times both at 0 degree C and at -20 degrees C may be mediated by the N-acetylgalactosamine moiety of the AFGP, but is strongly amplified by the polypeptide. PMID- 8452861 TI - Kinesin is rapidly transported in the optic nerve as a membrane associated protein. AB - We have investigated the membrane vs. cytosolic distribution of newly synthesized and total kinesin in rabbit retinal ganglion cell axons which comprise the optic nerve. We find that kinesin is rapidly transported into the axon and that this newly synthesized protein is completely membrane-associated while approximately two third of the total kinesin in the optic nerve is membrane associated. Of this membrane associated kinesin about half is resistant to removal by treatment with 100 mM Na2CO3 (pH 11.3) and none can be stripped by 1 M NaCl. The newly synthesized axonal kinesin is completely resistant to removal by Na2CO3 treatment. By these criteria, at least one third of the total and essentially all of the rapidly transported axonal kinesin appears to exist as an integral membrane protein, consistent with it functioning as the anterograde motor for rapid vesicle transport from the cell body through the axon. PMID- 8452862 TI - The mode of action of primary bile salts on human platelets. AB - Cholate and its conjugated amide derivatives glycocholate and taurocholate solubilized human platelets differently as studied by the observations on: (1) the change in optical absorbance of platelet suspension, (2) marker leakiness and (3) component solubility. Cholate ruptures the membrane in an all-or-none process, while both conjugated derivatives shed off both proteins and lipids. The shed lipids formed vesicles and could be separated from the proteins. The conjugated salts gradually chop off the cell membrane into pieces causing the cells to become small spheres (1.5 microns in diameter) as revealed by scanning electron microscopy, which also revealed that morphological change of platelet in these bile salts depended on both concentration and incubation period. Platelets at the prelytic-stage concentration of these three salts deformed initially to spiculate disc and finally to a stretched-out flat form. Also, in the prelytic stage of these bile salts, platelets showed inhibited responses to thrombin which did not happen to platelets in deoxycholate (Shiao et al. (1989) Biochim. Biophys. Acta 980, 56-68.). PMID- 8452863 TI - Translocation of fluorescent ether phospholipid, but not its diacyl counterpart, after insertion in plasma membranes of control and plasmalogen-deficient fibroblasts. AB - Fluorescently labelled ether phospholipid (1-O-alkyl/alkenyl-2-acyl- glycerophosphocholine) readily internalizes at low temperatures (2 degrees C) after insertion into the plasma membrane of cultured fibroblasts. This fate differs markedly from that of its diacyl phospholipid analogue, which remains associated with the plasma membrane under similar conditions. Analysis by thin layer chromatography reveals that the translocation involves transfer of the intact ether phosphatidylcholine molecules. Relative to control cells, a 2-fold increase of ether phosphatidylcholine uptake was noted when plasmalogen deficient fibroblasts were used. Back-exchange experiments demonstrate that more than 60% of the cell-associated ether lipid is translocated within the cells, irrespective of the cell strain that was used. The potential mechanism by which the translocation process is accomplished is discussed. PMID- 8452864 TI - Interaction of the yeast phosphatidylserine transfer protein with artificial and biological membranes. AB - Transfer of pyrene-labeled phosphatidylserine catalyzed by the yeast phosphatidylserine transfer protein in vitro largely depends on the membrane lipid composition of artificial unilamellar acceptor vesicles. Negatively charged phospholipids markedly decrease the rate of protein-catalyzed phosphatidylserine transfer. Although biological membranes contain a significant proportion of negatively charged phospholipids they serve more effectively as acceptors than artificial membranes with a similar phospholipid composition, but without proteins. This result indicates that proteins present in biological membranes mask negative charges of phospholipids on the surface of acceptor membrane vesicles. When proteins of the membrane surface are removed by proteinase treatment this protective effect is partially lost. A correlation between the activity of the phosphatidylserine transfer protein in yeast cytosol and the extent of membrane biogenesis during growth could not be observed. PMID- 8452865 TI - Cytolytic effects and biochemical changes induced by extracellular ATP to isolated hepatocytes. AB - Cell death, as estimated by the release of lactate dehydrogenase (LDH), was induced by incubating isolated hepatocytes for 60 min in the presence of extracellular ATP (ecATP), while AMP, adenosine, GTP and UTP were without any significant effects, even when tested at 3 mM (final concentration). At such a concentration, the release of LDH induced by ecATP, but also by ecADP, reached almost 50% and 30%, respectively. Since UTP and GTP (which have no lytic effects) were able to activate phosphorylase a at the same rate as ATP, we excluded the possibility that an increase of free cytosolic Ca2+ triggers the onset of a process leading to cell lysis. Moreover, such a lytic ability of ecATP (1.7 mM) can not be the result of a previous complexation of ionic iron (making it catalytically available for a Fenton reaction), because Desferal, a strong iron chelator, did not modify the cytolytic effect of the ecATP observed after 60 min of incubation. A major cellular function such as protein synthesis was impaired in a dose-dependent way by incubating hepatocytes during 60 min in the presence of ecATP. The inhibition was already observed at 0.1 mM ecATP, a dose without any effect on cell viability. The biological relevance of such metabolic impairment, however, remains to be elucidated. PMID- 8452867 TI - Modulation of the plasminogen activation system in murine macrophages. AB - We have dissected the state of fibrinolytic balance in the C57/BL mouse macrophages, by means of immunotrap assays and zymography. We have monitored the individual changes of plasminogen activator (PA) and plasminogen activator inhibitor (PAI) activities of cellular lysates and secretions of these macrophages, after they were stimulated by various exogenous agents. The resident peritoneal macrophages were found to have very little PA but high level of PAI, and are therefore highly anti-fibrinolytic in nature. Upon stimulation by thioglycollate, PA activity increased and PAI activity decreased, thus raising the fibrinolytic balance in these macrophages. Upon incubation of resident or thioglycollate-activated macrophages by lipopolysaccharide (LPS), the PA level was depressed while the PAI level was increased, resulting in a large drop in the total fibrinolytic balance of the activated cells. When resident or thioglycollate-activated macrophages were incubated with the anti-inflammatory agent dexamethasone, the drug depressed both the expressions of PA and PAI, in the lysate and conditioned medium of both cell types. Thus cell-bound or secreted forms of macrophage PA and PAI activities were either increased or decreased in response to thioglycollate, LPS or dexamethasone challenge. The changes in PA and PAI resulted in different state of fibrinolytic balance in macrophages, and could be related to the different functions of these macrophages at different stages of their development. PMID- 8452866 TI - Utilization by human amniocytes for prostaglandin synthesis of [1 14C]arachidonate derived from 2-[1-14C]arachidonylphosphatidylcholine associated with human fetal pulmonary surfactant. AB - The phospholipids of human fetal pulmonary surfactant prepared from term amniotic fluid contained arachidonic acid and its utilization for prostaglandin synthesis by amnion cells has been investigated. Cells were incubated with surfactant labelled with L-alpha-1-palmitoyl-2-[1-14C]arachidonylphosphatidylcholine. The uptake of radioactivity into amniocyte phospholipids increased with time and with the concentration of surfactant and after 2 h of incubation at 37 degrees C, 63% of the incorporated radioactivity was recovered in phosphatidylethanolamine (PE) and phosphatidylinositol (PI). Similar results were obtained when amniocytes were incubated with liposomes prepared from lipid extracts of surfactant, but when cells were incubated with liposomes prepared from synthetic lipids the transfer of radioactivity to PE and PI was only 27%. Fetal surfactant contained platelet activating factor (PAF) but the addition of the antagonist hexanolamino-PAF did not affect either the uptake or intracellular redistribution of surfactant arachidonate by amniocytes, nor did the addition of PAF affect the results obtained with liposomes prepared with synthetic lipids. Cells preincubated with surfactant labelled with 2-[1-14]arachidonylPC released radioactive arachidonate and prostaglandin E2 when stimulated with calcium ionophore A23187 or with phorbol ester. These data demonstrate that surfactant provides a source of arachidonate that can be utilized by amnion cells for prostaglandin synthesis. PMID- 8452868 TI - Regulation of white adipocyte guanine nucleotide binding proteins Gs alpha and Gi alpha 1-2 by testosterone in vivo: influence of regional fat distribution. AB - The influence of the androgenic status on the steady-state amounts of Gi alpha 1 2 and Gs alpha subunits was compared in hamster fat cell membranes from the femoral subcutaneous (FSC) and epididymal (EP) adipose tissues, using immunoblotting experiments. In sham-operated hamsters, Gi alpha 1-2 and Gs alpha steady-state amounts found in FSC fat cells were 38% and 40% reduced, respectively, as compared to EP adipocytes. In EP fat cells, castration induced a down-regulation of both Gi alpha 1-2 (-39%) and Gs alpha (-33%), whereas testosterone replacement restored Gs alpha, but not Gi alpha 1-2 levels, to control values. In contrast, these G protein alpha-subunits were insensitive to the androgenic status in FSC fat cells. These data provide the first evidence that the androgenic status can modulate the expression of both the Gi alpha 1-2 and Gs alpha subunits of the fat cell adenylate cyclase regulatory Gi and Gs proteins and that this modulation depends on the anatomical origin of these cells. PMID- 8452869 TI - Phosphatidic acid stimulates the rolipram-sensitive cyclic nucleotide phosphodiesterase from rat thymocytes. AB - The role of phospholipid metabolites in the modulation of cyclic AMP degradation during the early response of rat thymic lymphocytes to mitogenic stimulation was investigated by measuring their in vitro effect on the activity of five different cyclic nucleotide phosphodiesterase forms separated from thymocyte cytosol by means of an HPLC technique. Arachidonic acid was found to markedly inhibit four of the enzyme forms, with IC50 ranging from 14 to 60 microM, while its hydroperoxy and hydroxy derivatives proved inefficient. Dioctanoylglycerol, a biologically active diacylglycerol, was weakly inhibitory while phosphatidic acid, the diacylglycerol phosphorylated derivative, markedly stimulated the two cyclic-AMP-specific type-IV forms identified in thymocyte cytosol, by 50 and 70%. In intact cells labelled with tritiated arachidonate, the mitogenic lectin concanavalin A induced a rapid 4-5-fold increase in radiolabelled phosphatidic acid which peaked at 1 min, and remained elevated for at least 30 min. These observations suggest that phosphatidic acid formed during the mitogenic stimulation of T-cells might be responsible for an early activation of cyclic AMP degradation with, as a consequence, a lowering of cyclic AMP level, which is reported to be necessary for the occurrence of the first steps of mitogenesis. PMID- 8452870 TI - Accessibility of hepatocyte protein thiols to monobromobimane. AB - The amino-acid residue specificity of monobromobimane (mBBr) and its accessibility to cellular protein cysteine residues were investigated. mBBr reacted selectively with the sulfhydryl group of both the free amino acid cysteine and bovine serum albumin. Incubation of isolated hepatocytes with mBBr resulted in a concentration-dependent formation of protein-bound mBBr fluorescence in the cytosolic, mitochondrial and microsomal fractions, which was not fully saturated with up to 16 mM mBBr. SDS-PAGE resolution of the proteins revealed that the major portion of increased protein-bound mBBr fluorescence that occurred at high mBBr concentrations was due to covalent binding to proteins. A minor portion (10-16% in the microsomal fraction) of protein-bound mBBr fluorescence was removed by SDS-PAGE and is therefore concluded to be due to physical entrapment of fluorescent mBBr reaction products. The accessibility of mBBr, assayed as the degree of depletion of total protein cysteine residues, was similar to N-ethylmaleimide (NEM) in isolated microsomes. By contrast, in the cytosol a markedly lower amount of protein cysteine residues were labelled by mBBr as compared to NEM. In both organelle fractions p-BQ was the most efficient thiol-depleting reagent. It is concluded that mBBr is a suitable reagent for the analysis of the cellular protein thiol status and of its xenobiotic-induced alterations when used at high concentrations; however, it should be considered that, (i) the relative accessibility of mBBr and a particular xenobiotic to cellular protein thiol residues may be different, and (ii) physically entrapped fluorescent reaction products of mBBr should be removed when quantitating protein thiol levels. PMID- 8452872 TI - An additional arginine-vasotocin-related peptide, vasotocinyl-Gly-Lys, in Xenopus neurohypophysis. AB - The neurohypophysis of Xenopus and that of Ranidae and Bufonidae contain hydrin 1 (vasotocinyl-Gly-Lys-Arg) and hydrin 2 (vasotocinyl-Gly), respectively. In order to test the aldosterone-releasing activity of arginine vasotocin (AVT) and hydrin 1, purification of these peptides from an acid-extract of the neurointermediate lobe of Xenopus laevis was performed using an ODS-silica cartridge and reverse phase and ion-exchange HPLC columns. As a result, an additional AVT-related peptide was newly found. Amino-acid analysis revealed that this peptide is vasotocinyl Gly-Lys (AVT-GK). The aldosterone-releasing activity of AVT-GK was equivalent to that of hydrin 1 (AVT-GKR) and lower than that of AVT. Like AVT and AVT-GKR, AVT-GK were effective in stimulating water flux from the isolated urinary bladder of the toad. Since AVT-GK is regarded as an intermediate between hydrin 1 and hydrin 2 in terms of its C-terminal form, it was designated hydrin 1'. PMID- 8452871 TI - Stimulation of glucose incorporation into glycogen by E-series prostaglandins in cultured rat hepatocytes. AB - In primary cultures of rat hepatocytes, 16,16-dimethylprostaglandin E2 (16,16 dimethyl PGE2), a biologically active analogue of prostaglandin E2 (PGE2), stimulated the basal rate of [14C]glucose incorporation into glycogen. 16,16 Dimethyl PGE2 caused concentration-dependent stimulation (ED50: 10(-8) M) with a maximum 2-3 h after its addition. Prostaglandin E1 (PGE1), PGE2 and prostaglandin F2 alpha (PGF2 alpha) stimulated also the incorporation, but less effectively than 16,16-dimethyl PGE2. However, prostaglandin D2 (PGD2) did not show such effect. Cellular glycogen analysis revealed that PGE2 and 16,16-dimethyl PGE2 increased a net glycogen accumulation time-dependently. Pretreatment of the cultured hepatocytes with pertussis toxin blocked the effects of PGE2 and 16,16 dimethyl PGE2 completely and concentration-dependently. These findings indicate that E-series prostaglandins have significant effects on hepatic glycogenesis via pertussis-toxin-sensitive G protein, in addition to their inhibitory effects on hormone-stimulated glycogenolysis reported previously (Okumura, T., Sago, T. and Saito, K. (1988) Prostaglandins 36, 463-475). PMID- 8452873 TI - Regulation of mouse serum amyloid P gene expression by cytokines in vitro. AB - Inflammation is accompanied by an increase in the plasma levels of a number of proteins collectively known as acute-phase reactants (APRs). Serum amyloid P component (SAP) is a major mouse APR: hepatic SAP mRNA and plasma SAP protein concentrations increase by up to 20-fold in mice undergoing an inflammatory response. In-vitro studies, using primary hepatocyte cultures, have previously shown that SAP mRNA and protein levels increase in response to stimulation with a variety of cytokines such as monocyte-conditioned medium (MCM), interleukin 1 (IL 1), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta). In this report, we have examined a mouse hepatoma cell line in which SAP gene regulation closely resembles that of primary hepatocytes. Accumulation of SAP mRNA in the +/+ Li mouse hepatoma cell line after stimulation with MCM, IL-1, IL-6 and the combination of IL-1 and IL-6 was demonstrated. This increase in the cellular content of SAP mRNA did not require new protein synthesis and was at least partially due to an increase in the transcription rate of the SAP gene. PMID- 8452874 TI - Regulation of adrenal and hepatic alpha-tocopherol content by androgens and estrogens. AB - Previous studies demonstrated that alpha-tocopherol concentrations were far greater in adrenal glands and in livers from female rats than in those from males. Studies were done to investigate the role of androgens and estrogens in the regulation of adrenal and hepatic alpha-tocopherol content. In males and females, adrenal concentrations of alpha-tocopherol were approx. 10-fold greater than those in liver and the highest concentrations of alpha-tocopherol were in the crude mitochondrial fractions in both organs. Castration of female rats decreased alpha-tocopherol concentrations in adrenals and in livers. Proportionately similar declines occurred in both organs and in all subcellular fractions. The effects of castration were prevented by estradiol replacement at the time of surgery. Gonadectomy in male rats had effects opposite to those in females, increasing adrenal and hepatic alpha-tocopherol concentrations. Testosterone administration to castrated males prevented the increases in adrenal and hepatic alpha-tocopherol content. Neither castration nor gonadal hormone replacement in either sex had any effect on plasma alpha-tocopherol levels or on cytosolic ascorbic acid concentrations in adrenals or livers. The results indicate a role for estrogens and androgens in the regulation of adrenal and hepatic concentrations of alpha-tocopherol. The opposing effects of androgens and estrogens fully account for the sex differences in tissue alpha-tocopherol levels in rats. PMID- 8452875 TI - Tumor necrosis factor alpha-induced alteration of glycosaminoglycans in cultured vascular smooth-muscle cells. AB - We studied alteration of glycosaminoglycans (GAGs) induced by recombinant human tumor necrosis factor alpha (rhTNF alpha) in vascular smooth-muscle cells from bovine aorta in a culture system. It was found that rhTNF alpha at 10 ng/ml and below significantly increased the incorporation of [35S]sulfate (35S) but conversely decreased that of [3H]glucosamine (3H) into GAGs in the trypsinate fraction of the cell layer after a 24-h incubation. These results suggested that rhTNF alpha reduced the formation and/or the anchorage of sugar chains in the cell layer but enhanced their sulfation in whole GAG synthesis by the cells. In results, the ratio of 35S to 3H in the GAGs was markedly increased. This increase occurred after 24 h and longer when the cells were treated with 1.0 ng/ml rhTNF alpha. The TNF alpha-induced alteration of the incorporation of both 35S and 3H was completely blocked by anti-rhTNF alpha antibody. Other cytokines including recombinant human interleukin-1 beta and -6, and platelet-derived growth factor failed to alter the ratio of 35S to 3H in the GAGs of the trypsinate fraction of the cell layer. In cultured vascular endothelial cells from bovine aorta, however, rhTNF alpha at 1.0 ng/ml significantly decreased the incorporation of both 35S and 3H into GAGs of both the trypsinate fraction and the medium; the ratio of 35S to 3H was not changed. Characterization of GAGs in vascular smooth muscle cell trypsinate fraction revealed that rhTNF alpha at 10 ng/ml induced (i) no change of the incorporation of 3H in the hyaluronate fraction, (ii) a marked increase in the incorporation of 35S and no change of that of 3H in chondroitin sulfates (A plus C) fraction, (iii) a significant decrease in the incorporation of both 35S and 3H in the heparan sulfate fraction, and (iv) no change of the incorporation of 35S and a marked decrease in that of 3H in the dermatan sulfate fraction. In the medium, rhTNF alpha also induced various changes of GAGs. It was therefore concluded that TNF alpha may have a capacity of inducing a qualitative change of vascular smooth-muscle cell GAGs, which may be involved in the vascular pathology such as atherosclerosis. PMID- 8452876 TI - Glycosphingolipid patterns in human promyelocytic HL-60 leukemia cells susceptible or resistant to differentiation induction by phorbol 12-myristate 13 acetate. AB - The patterns of glycosphingolipids (GSLs) were analyzed in an HL-60 cell variant, HL-205, which is susceptible to phorbol 12-myristate 13-acetate (PMA)-induced monocyte/macrophage differentiation, and in an HL-60 cell variant, HL-525, which is resistant to such differentiation. The amounts and types of the GSLs were similar in both the HL-205 and HL-525 cells and they resemble those of granulocytes. Treatment with 3 nM PMA caused the susceptible HL-205 cells (but not the resistant cells) to acquire a new GSL pattern which resembles that of monocytes. This new pattern was characterized by increases in the level of a neutral GSL, Gb3Cer, from trace levels to 0.05 mg/10(9) cells and of an acidic GSL, GM3 ganglioside, from 0.03 to 0.33 mg/10(9) cells. The increases in the level of this ganglioside were found to be due to an increase in CMP-N acetylneuraminic acid:lactosylceramide sialyltransferase activity. These results indicate an association between PMA-induced terminal differentiation along the monocyte/macrophage cell lineage and PMA-evoked increases in specific GSLs, GM3 in particular, which is due to a rise in the activity of its synthetic enzyme. PMID- 8452877 TI - Activation of K+/Cl- cotransport in human erythrocytes exposed to oxidative agents. AB - Activation of K+/Cl- cotransport was studied after exposure of normal human erythrocytes to the oxidative action of acetylphenylhydrazine (APH), menadione sodium bisulfite (MSB), hydrogen peroxide (H2O2) or phenazine metasulfate (PMS). In order to better define the relative contributions of K+/Cl- cotransport on ouabain and bumetanide-resistant (OBR) K+ efflux induced by oxidation, we used (dihydroindenyl)oxyalkanoic acid (DIOA) and carbocyanine as specific inhibitors, respectively, of cotransport system and Ca(2+)-activated K+ channel. APH, MSB and - to much less extent - H2O2 promoted a K+ efflux pathway with features corresponding to those of K+/Cl- cotransport. This pathway showed: (i) kinetics of efflux compatible with a specific cation transport system; (ii) requirement for chloride anion; (iii) resistance to ouabain, bumetanide and carbocyanine inhibition; (iv) stimulation by hypotonic challenge; (v) susceptibility to inhibition by DIOA. Dithiothreitol (DTT) or 2-mercaptoethanol (2-ME) decreased K+/Cl- cotransport activation, suggesting that oxidative mechanisms affected crucial SH groups of the transporter. These data suggest that oxidation represents a factor capable of modulating activation of K+/Cl- cotransport. Its possible contribution in situations with high oxidative risk, such as sickle-cell anaemia or beta thalassemia, is discussed. PMID- 8452878 TI - Conversion of liposomal 5-fluoro-2'-deoxyuridine and its dipalmitoyl derivative to bile acid conjugates of alpha-fluoro-beta-alanine and their excretion into rat bile. AB - We studied the hepatic processing and biliary excretion of metabolites of the radiolabeled cytostatic agent 5-fluoro,-2'-deoxy[6-3H]uridine (FUdR) and its lipophilic derivative FUdR-dipalmitate incorporated in liposomes. After intracardial injection in rats, free FUdR was cleared from the circulation within minutes. When FUdR or FUdR-dipalmitate was encapsulated in multilamellar vesicles (MLVs) composed of distearoylphosphatidylcholine/dipalmitoylphosphatidylglycerol (DSPC/DPPG/CHOL, 10:1), as expected, the clearance of 3H label was substantially delayed; incorporation of 50 mol% cholesterol in the liposomal bilayer caused a 2 fold further reduction in elimination rate. Incorporation of FUdR-dipalmitate in small unilamellar vesicles (SUV) of similar composition produced a several-fold further decrease in elimination rate: more than 40% of the injected dose was still circulating after 6 h. The plasma concentration of free FUdR after administration of liposomal FUdR-dipalmitate was below the detection limit (5 x 10(-8) M) at any time. Although only about 9% of the administered radioactivity was excreted into the bile within 48 h after injection of [3H]FUdR, a rapid initial excretion rate was observed (4% of the injected dose in the first 2 h). The bile-associated radioactivity was identified mainly as the catabolite alpha fluoro-beta-alanine (FBAL), conjugated with the three major bile acid species present in rat bile, i.e., muricholic acid, cholic acid and chenodeoxycholic acid in a ratio of 1:3:1. Liposome incorporation of FUdR or FUdR-dipalmitate did not affect the nature of the excretory products but caused a significant decrease in the initial rate at which label appeared in the bile (< 2% in 6 h). PMID- 8452879 TI - Transcript levels of thymosin beta 4, an actin-sequestering peptide, in cell proliferation. AB - Thymosin beta 4 (beta 4) is an ubiquitous 5-kDa peptide that has been identified as an actin-sequestering peptide. In this work, Northern blot analysis was used to study the beta 4 mRNA levels during the cell cycle of rat thymocytes and hepatocytes as well as in human lymphocytes from patients with leukemia. beta 4 mRNA was found in all the stages of thymocyte and hepatocyte cell cycle, showing an increase in the S-phase which was maintained during the G2 and M phases. Incubation of splenic T-cells with concanavalin A, phorbol myristate acetate or the ionophore A23187 lead to a similar increase of beta 4 transcript during the S phase. The increase in beta 4 mRNA observed in the G2/M boundary of the cell cycle, together with its ability to inhibit actin polymerization, suggests a possible role of beta 4 in the the morphological changes and actin redistribution occurring during the cytokinesis. PMID- 8452880 TI - The mechanism of arachidonic acid-induced insulin secretion from rat islets of Langerhans. AB - The stimulation of rat pancreatic islets by glucose leads both to the secretion of insulin, and the production of arachidonic acid (AA). We have previously shown that exogenous AA can stimulate insulin secretion and that this secretion was not dependent upon extracellular Ca2+ nor upon the activation of protein kinase C. We have now demonstrated that AA-induced insulin secretion was a saturable and reversible process. AA-stimulated insulin secretion was slow in onset from intact islets but immediate from electrically permeabilized islets. In permeabilized islets AA-induced insulin secretion was not dependent on changes in intracellular Ca2+ or ATP and was not inhibited by noradrenaline. These results suggest that AA affects insulin secretion at a late stage in the exocytotic process. PMID- 8452881 TI - Cell cycle-related expression of poly(ADP-ribosyl)transferase in proliferating rat thymocytes. AB - The activity profile of poly(ADP-ribosyl)transferase was assayed during a complete cell cycle of rat thymocytes stimulated in the presence of interleukin-2 by concanavalin A or monoclonal antibodies against the T-cell antigen receptor (TCRmAB). Poly ADP-ribosylation was measured in permeabilized cells by the incorporation of [adenine-3H]NAD+ into protein bound poly ADP-ribose. The polymers of ADP-ribose were separated from the monomers using dihydroxyboronyl Bio-Rex 70 columns. The rate of poly(ADP-ribosyl)ation increases during the G1 phase with a maximum 12 h after stimulation. This increase in activity is due to enhanced de novo synthesis of poly(ADP-ribosyl)transferase which can be abolished by the addition of cycloheximide. The half-life of this enzyme during the induction period was estimated to be 4 h. A second activity peak appears during the S-phase of the cell cycle 48 h after stimulation. The maxima of the poly(ADP ribosyl)ation rate coincide with elevated immunoreactive enzyme levels at 12 and 48 h of culture assayed by Western blotting. The mRNA levels of pADPRT do not correlate with the first maximum of activity, whereas the second maximum was accompanied by a 5-fold increase of the specific mRNA. These results suggest a translational regulation of pADPRT in the G1 phase of the cell cycle, whereas the second activity peak in the S-phase is due to an increased transcription and translation. The induction of pADPRT activity in the G1 phase of TCRmAB stimulated cells points to a function of poly(ADP-ribosyl)ation in the proliferation of thymocytes. PMID- 8452882 TI - Nucleotides mobilize intracellular calcium stores of renal proximal cells in primary culture: existence of a suramin-sensitive mechanism. AB - Changes of intracellular calcium concentrations [Ca2+]i were measured in primary cultured rabbit proximal convoluted tubules (PCT). A dual-excitation, digital imaging inverted microscope was used to monitor the fura-2 fluorescence. The basal calcium level was 106 +/- 11 nM (n = 36). The stimulatory effects of adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine were studied. ATP and ADP induced transient increases of [Ca2+]i (1059 +/- 115% of the resting level (n = 29), and 659 +/- 134% (n = 10), respectively) by releasing calcium from cytoplasmic stores. Adenosine had less effect (279 +/- 48% of the resting level, n = 3). In the same conditions the ATP antagonist suramin (100 microM) inhibited the action of ATP and ADP to 231 +/- 52% (n = 3), and 308 +/- 29% (n = 4) of the resting level, respectively, but did not modify that of adenosine (281 +/- 72%, n = 3). A pretreatment (500 ng/ml for 2 h at 37 degrees C) of the culture with the toxin of Bordetella pertussis completely blocked the ATP response. Our results are evidence for the presence of a functional suramin sensitive ATP and ADP puriceptor in cultured renal proximal cells. A pertussis toxin-sensitive G protein is linked to the transduction mechanism. This receptor is distinct from an adenosine puriceptor also found in the proximal monolayer. PMID- 8452883 TI - Uptake of tyramine by rat hepatocytes. AB - Observations on the uptake of tyramine by hepatocytes indicate that the amine is taken up by simple diffusion and a transporter mediated system, with a Km of 39 microM and a Vmax of 270 pmol/min/10(5) cells. The carrier-mediated process is pH and temperature-dependent and requires an activation energy of 12.9 kcal/mol. An overshoot uptake is achieved a few minutes after adding this amine to the cell suspension, suggesting that active transport is involved. This is supported by the finding that partial inhibition of the uptake can be induced by oligomycin, azide, cyanide and dinitrophenol. NO3-, SCN- and SO4(2-), which change the membrane potential significantly, and depress the transporter mediated uptake further, suggesting that the membrane potential is the driving force for the entry of this amine across hepatic membrane. Cysteine is essential for the normal carrier function; whereas, histidine, tryptophan, arginine and lysine do not directly deal with the activity of the carrier. Many substances, but not amino acids, H, M, and N receptor agonists, can inhibit the uptake of tyramine. It is possible that other amines can enter hepatocytes by using this transporter. PMID- 8452884 TI - Superoxide dismutase and thioredoxin restore defective p34cdc2 kinase activation in mouse two-cell block. AB - We recently showed that superoxide dismutase (SOD), a free radical scavenger, and thioredoxin, a potent protein disulfide reductase, release mouse two-cell stage developmental block in vitro. To elucidate the mechanism underlying the two-cell block and the effects of these enzymes, we studied the chronological changes in the kinase activity and the immunoblotting pattern of p34cdc2, a key regulator of the cell cycle, during the first and second cell cycles of the mouse embryonic development. In vivo embryos were freshly collected at fixed times, and in vitro embryos cultured from the pronuclear stage were also sampled with the same time course. A marked elevation of p34cdc2 kinase activity was observed in vivo at 27 32 and 51 h after an injection of human chorionic gonadotropin. These times coincide with the M-phases of embryo cleavage. In vitro embryos showed high kinase activity during the M-phase of the first cleavage, but this activity was not elevated during the second cell cycle. The addition of recombinant human SOD (200 micrograms/ml) or thioredoxin from Escherichia coli (500 micrograms/ml) to the medium enabled kinase activation with a time course similar to that of in vivo embryos. The immunoblotting patterns suggested the dephosphorylation of p34cdc2 at the M-phase of the first and the second cleavages in vivo. Although p34cdc2 was dephosphorylated at the M-phase of the first cleavage and then rephosphorylated for embryos cultured in vitro, the second dephosphorylation was not observed during the second cell cycle. The addition of SOD or thioredoxin permitted the dephosphorylation at the M-phases of both the first and the second cleavage. These results suggest that one of the chief causes of two-cell block in vitro is the impairment in p34cdc2 dephosphorylation, recently shown to be catalyzed by the cdc25 homologue. This impairment is thought to be due to oxidative stress, because both SOD and thioredoxin are known to play a defensive role against it. PMID- 8452886 TI - Further study on 1/f fluctuations observed in central single neurons during REM sleep. AB - Recently, 1/f fluctuations have been discovered in the single-unit activity of mesencephalic reticular formation (MRF) neurons during REM sleep. In a previous paper, such behavior could satisfyingly be interpreted on the basis of the clustering Poisson process. The question of applicability of this model to other MRF neurons remained unanswered. The present paper reports on 1/f fluctuations in 12 MRF neurons all of which can satisfyingly be modeled by the clustering Poisson process. PMID- 8452885 TI - Requirement of cytoplasmic components for lidocaine-induced shape change in human erythrocytes. AB - To clarify the mechanism underlying local anesthetic-induced changes in the shape of human erythrocytes from discocytes to stomatocytes, we treated erythrocytes with lidocaine, a cationic drug. Analysis of the erythrocyte membrane and cytoplasm by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) revealed that the intensities of the stained bands of 62 kDa, 28 kDa and 22 kDa depended on the extent of the shape change induced by lidocaine. The change in the intensity of the 28 kDa band was particularly marked. We identified the cytoplasmic substances, i.e., the 28 kDa and 22 kDa peptides, as carbonic anhydrase (CA) and glutathione peroxidase (GSH Px)1, respectively, by immunoblotting. The 62 kDa peptide was identified as Hb by column chromatography and SDS-PAGE analysis. To identify the protein responsible for the lidocaine induced shape change, we incorporated CA and GSH Px into ATP-MgCl2-resealed ghosts. The shape of the resealed ghosts changed upon addition of lidocaine, but only in the presence of CA. These results suggest that ATP and CA are required for the shape changes induced by lidocaine. PMID- 8452887 TI - 'Vector white noise': a technique for mapping the motion receptive fields of direction-selective visual neurons. AB - A technique is described and tested for mapping the sensitivities and preferred directions of motion at different locations within the receptive fields of direction-selective motion-detecting visual neurons. The procedure is to record the responses to a number of visual stimuli, each stimulus presentation consisting of a set of short, randomly-oriented, moving bars arranged in a square grid. Each bar moves perpendicularly to its long axis. The vector describing the sensitivity and preferred direction of motion at each grid location is obtained as a sum of the unit vectors defining the directions of motion of the bars in each of the stimuli at that location, weighted by the strengths of the corresponding responses. The resulting vector field specifies the optimum flow field for the neuron. The advantage of this technique over the conventional approach of probing the receptive field sequentially at each grid location is that the parallel nature of the stimulus is sensitive to nonlinear interactions (such as shunting inhibition for mutual facilitation) between different regions of the visual field. The technique is used to determine accurately the motion receptive fields of direction-selective motion detecting neurons in the optic lobes of insects. It is potentially applicable to motion-sensitive neurons with highly structured receptive fields, such as those in the optic tectum of the pigeon or in area MST of the monkey. PMID- 8452888 TI - Spike initiation and propagation on axons with slow inward currents. AB - We investigate spike initiation and propagation in a model axon that has a slow regenerative conductance as well as the usual Hodgkin-Huxley type sodium and potassium conductances. We study the role of slow conductance in producing repetitive firing, compute the dispersion relation for an axon with an additional slow conductance, and show that under appropriate conditions such an axon can produce a traveling zone of secondary spike initiation. This study illustrates some of the complex dynamics shown by excitable membranes with fast and slow conductances. PMID- 8452889 TI - Information theoretic analysis of action potential trains. I. Analysis of correlation between two neurons. AB - A crosscorrelational method of action potential trains has been proposed, based on information theory. Two information theoretic quantities, mutual information and channel capacity, were calculated from a pair of action potential trains for detecting a crosscorrelation and estimating synaptic connectivity. The method was compared with conventional ones, using action potential trains obtained by the simulation of a neuron model. This method was shown to have the advantages to more easily find a weak but significant crosscorrelation and to give better estimation of synaptic connectivity independent of the firing probability of a presynaptic neuron. PMID- 8452890 TI - The relationship between absolute disparity and ocular vergence. AB - The relationship between disparity and ocular vergence was investigated under closed-loop as well as under open-loop viewing conditions. First we examined whether vergence responded similarly to disparity presented under open-loop and closed-loop conditions. Similar response were observed in both conditions. The direct relationship between disparity and vergence was examined by presenting constant disparities between 0.2 degrees and 4 degrees under open-loop viewing conditions. Such vergence responses are described as the outputs of first-order low-pass filters with different filter characteristics for each amplitude of disparity. By analyzing the latency of vergence responses induced by constant disparities with help of the transfer function of disparity-controlled vergence, the time delay of disparity processing in the vergence loop was estimated. We suggested that the time delay was approximately between 80 and 120 ms instead of 160 ms as is generally assumed. The relationship between the rate of disparity change and vergence was examined by comparing responses to ramp and stepwise changes in target vergence. From the similar responses to ramp and staircase changes in disparity we concluded that vergence is not sensitive to the velocity of target vergence as such. On the basis of these findings we developed a model of disparity-controlled vergence. In this model disparity is processed through several parallel, imperfect integrators with slightly different low-pass filter characteristics, each of them susceptible to a limited range of disparities. Gains as well as phase lags of vergence responses to sinusoidal disparities are accurately simulated by this model.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452891 TI - Level dependent signal flow in the light pupil reflex. I. Latency of time domain responses to transient stimuli. AB - Latency of pupillary responses to light stimuli are smaller for larger steps of light, and larger for smaller steps of light (Alpern 1954; Lowenstein et al. 1964; Lee et al. 1969; Terdiman et al. 1969; Cibis et al. 1977; and many others). Miller and Thompson (1978), however, reported negligible change in pupil cycle time (period of high gain instability oscillations) with increased mean brightness. Sandberg and Stark (1968) reported a negligible reduction in phase lag of pupillary responses to sinusoidal light stimuli as the modulation coefficient (m) increased. To resolve the inconsistency between the well documented dependence of latency upon brightness, and the apparent absence of level dependence in the phase characteristics (as reflected directly in the responses to sinusoidal stimuli and indirectly in pupil cycle time experiments) we measured: 1. Latency to step stimuli of light, 2. Phase of responses to sinusoidal light stimuli and 3. Period (pupil cycle time) of high gain instability oscillations. The dependence of pupillary latency upon stimulus level (both light and accommodation) and the interaction between accommodation and light responses were investigated. We show that most of the level dependence of light-pupil latency resides in the afferent path. In the companion papers, we demonstrate that: 1. Phase of pupillary response to sinusoidal light stimuli is reduced by increased mean light level, but is independent of pupil size and accommodative stimulus level; and 2. The period of high gain oscillations is shown to decrease with increased mean light level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452892 TI - Level dependent signal flow in the light pupil reflex. II. Phase velocity of responses to sinusoidal light stimuli. AB - Pupillary responses to sinusoidal light stimuli were measured over a range of light levels and frequencies. The phase lag and equivalent time delay of these responses were reduced in an approximately log-linear fashion with increasing mean light level (slope = -60 ms/log unit). The magnitude of this level dependence is reduced at higher frequencies, and at higher light levels. This nonlinear level dependent signal flow (LDSF) effect is shown to be essentially independent of target distance (accommodative stimulus) which influences pupil size, and of pupil size itself. Thus most of the level dependence probably resides in the afferent path of the light-pupil reflex arc, before the accommodation signal joins the light signal in the Edinger-West-phal nucleus. A systems model is presented to the LDSF effect described here and in the companion papers (Myers and Stark 1993a, b). When parameters of the model are adjusted to fit pupillary responses to transient light stimuli over a range of light levels, the model simulates reduced phase lag in response to increased mean light level, and the reduction in this LDSF effect with increased mean light level or increasing stimulus frequency without further changes in parameters. This latter reduction explains the relatively small level dependence seen in latency data ( 34 ms/log unit). These data will be shown (Myers and Stark 1990b) to be commensurate with reduction in pupil cycle time (increased frequency of oscillation) observed in high gain oscillation experiments as mean brightness increases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452893 TI - Level dependent signal flow in the light pupil reflex. III. Phase velocity in high gain instability oscillations. AB - The pupil can be excited to sustained oscillations under high gain feedback conditions. The period of these oscillations (cycle time) is reduced by increased average light level by an amount commensurate with reductions in phase lag reported in the companion paper (Myers et al. 1991b). A mathematical model of this phenomenon is used to unify and clarify experimental data presented here and in the literature. PMID- 8452894 TI - A neural network model for visual motion detection that can explain psychophysical and neurophysiological phenomena. AB - This paper proposes a new neural network model for visual motion detection. The model can well explain both psychophysical findings (the changes of displacement thresholds with stimulus velocity and the perception of apparent motion) and neurophysiological findings (the selectivity for the direction and the velocity of a moving stimulus). To confirm the behavior of the model, numerical examinations were conducted. The results were consistent with both psychophysical and neurophysiological findings. PMID- 8452895 TI - Solvability of the electrocardiology inverse problem for a moving dipole. AB - New formulations of the direct and inverse problems for the moving dipole are offered. It has been suggested to limit the study by a small area on the chest surface. This lowers the role of the medium inhomogeneity. When formulating the direct problem, irregular components are considered. The algorithm of simultaneous determination of the dipole and regular noise parameters has been described and analytically investigated. It is shown that temporal overdetermination of the equations offers a single solution of the inverse problem for the four leads. PMID- 8452896 TI - Quantification and statistical verification of neuronal stimulus responses from noisy spike train data. AB - Usually neuronal responses to short-lasting stimuli are displayed as peri stimulus time histogram. The function estimated by such a histogram allows to obtain informations about stimulus-induced postsynaptic events as long as the interpretation is restricted to the first response component after the stimulus. The interpretation of secondary response components is much more difficult, as they may be either due to stimulus effects or represent an "echo" of the primary response. In the present paper two output functions are developed that do not show such an echoing of responses. The first one, the interspike interval change function, represents an ideal way to quantify a neuronal stimulus response as its amplitude was found to be almost independent of the stimulation strategy used during acquisition of the spike train data. The other function, the displaced impulses function, allows to verify the statistical significance of an observed response component. Both functions may be estimated from stimulus-correlated spike train data, even if the neuron under investigation shows considerable interspike-interval variability in the absence of stimulation. The concepts underlying these neuronal output functions are developed on simulated responses of a Hodgkin-Huxley-type model for a mammalian neuron at body temperature that is exposed to a transient excitatory conductance increase. Additionally, estimation of these output functions is also demonstrated on responses of human soleus motoneurons that were exposed to electrical stimuli of the tibial nerve in the popliteal fossa. PMID- 8452897 TI - A neurophysiologically-based mathematical model of flash visual evoked potentials. AB - Evidence is presented that a neurophysiologically-inspired mathematical model, originally developed for the generation of spontaneous EEG (electroencephalogram) activity, can produce VEP (visual evoked potential)-like waveforms when pulse like signals serve as input. It was found that the simulated VEP activity was mainly due to intracortical excitatory connections rather than direct thalamic input. Also, the model-generated VEPs exhibited similar relationships between prestimulus EEG characteristics and subsequent VEP morphology, as seen in human data. Specifically, the large correlation between the N1 amplitude and the prestimulus alpha phase angle, and the insensitivity of P2 to the latter feature, as observed in actual VEPs to low intensity flashes, was also found in the model generated data. These findings provide support for the hypothesis that the spontaneous EEG and the VEP are generated by some of the same neural structures and that the VEP is due to distributed activity, rather than dipolar sources. PMID- 8452898 TI - Cohort and nested case-control studies of hematopoietic cancers and brain cancer among electric utility workers. AB - Recent studies have raised concern about the potential health effects of occupational exposures to power frequency electric and magnetic fields. We evaluated cancer mortality for leukemia, brain cancer, and lymphoma from 1960 to 1988 in a cohort of 36,221 electric utility workers using cohort analyses and three nested case-control studies. From a volunteer sample of the current workforce that represented a variety of different occupations and work locations, we collected 776 days of magnetic field measurements. We derived exposure information from company job history information and developed exposure scores by linking job history data to measured magnetic fields. In job title analyses, we compared "electrical workers" with other field and craft occupations, office, and technical support staff. Age-specific cancer rates for electrical and reference workers were similar. "Electrical workers" had rate ratios or odds ratios ranging from 0.7 to 1.4. Most ratios were close to 1.0. Lymphomas were slightly elevated compared with leukemias and brain cancers (ratios of 0.9-1.4 vs 0.7-1.2, respectively). Odds ratios for magnetic field exposure indices, based on scores for the mean, median, 99th percentile, and fractions exceeding 10 milligauss and 50 milligauss, were all close to or less than 1.0. The interval estimates indicate no strong association but are somewhat limited by imprecision. PMID- 8452899 TI - Prior injury and motor vehicle crash as risk factors for youth suicide. AB - We conducted a case-control study to determine whether adolescents and young adults who have been in a motor vehicle crash or hospitalized for unintentional and intentional injury are at greater risk for suicide. Cases were 700 Washington State residents age 16-35 with a driver's license who died of suicide during 1987 1989. Controls were 3,494 licensed drivers matched by age, sex, and zip code. Using two different databases, we were able to determine the past incidence of in state injury hospitalizations and motor vehicle crashes for all subjects. Overall, the incidence of suicide was tenfold higher among those with a past hospitalization for injury. Many of these admissions were for suicide attempts [odds ratio (OR) = 56, 95% confidence interval (CI) = 27-120], but the risk of suicide was also higher among those hospitalized for unintentional injuries (OR = 5.0, 95% CI = 2.2-11.5) and assaults (OR = 4.5, 95% CI = 1.1-18). The relative risk for suicide was 2.7 (95% CI = 2.0-3.5) for those with prior injury as a driver in a motor vehicle crash and 2.9 (95% CI = 2.2-3.8) for those with involvement in a single vehicle crash. Many unintentional injury hospitalizations and a proportion of motor vehicle crashes in younger adults may represent unrecognized suicide attempts. PMID- 8452900 TI - Cox regression models for intermediate events, with discharge from hospital as an example. AB - In studies of mortality or morbidity of hospitalized patients, discharge from hospital is an intermediate event between hospital experience and disease outcomes, as disease onset may occur after release from hospital. This study explored the role that discharge might have in risk for surgical infections after hernia repair operations, where follow-up continued for 1 month after operation, and 50% of infections occurred at home. Possible direct and interactive effects were evaluated in the presence of two major methodologic difficulties: waiting time bias, because patients became candidates for home infections only after leaving the hospital, and selective discharge bias, because discharge carried much prognostic information. It was possible, using Cox models, to correct for the waiting-time bias, but the strong protective effect of termination of hospitalization on the risk for infection remained difficult to interpret. The strengths and limitations of various Cox models in dealing with these issues are discussed. PMID- 8452901 TI - Caffeine and other predictors of bone density among pre- and perimenopausal women. AB - We evaluated the influence of dietary, anthropomorphic, and hormonal factors on bone density in a cross-sectional sample of 281 pre- and perimenopausal women age 50-60 years living in Massachusetts. The sample included only women who had intact ovaries and were not currently using estrogen. Information on diet was obtained through a semiquantitative food frequency questionnaire. We measured bone density using single-photon absorptiometry in the non-dominant arm in two sites: the midshaft and the ultradistal radius. We observed no important associations between midshaft bone density and dietary variables but found linear relations between ultradistal radius bone density and body mass index [b = 1.10 gm/cm2 per kg/m2, standard error (SE) = 0.56], follicle-stimulating hormone (FSH) (b = -0.36 gm/cm2 per IU/liter, SE = 0.15), and several nutrients: calcium (b = 0.012 gm/cm2 per mg/day, SE = 0.007), retinol (b = 0.002 gm/cm2 per IU/day, SE = 0.0008), vitamin C (b = 0.025 gm/cm2 per mg/day, SE = 0.013), and vitamin D (b = 0.040 gm/cm2 per IU/day, SE = 0.018). We could not clearly distinguish the independent contribution of these micronutrients, however, because many were commonly ingested together in the form of supplements. Caffeine was inversely associated with bone density (b = -0.035, SE = 0.017) independent of dietary, anthropometric, and hormonal factors. Analyses of individual caffeinated beverages revealed consistent inverse associations for coffee (b = -3.42 gm/cm2 per cups/day, SE = 1.49), tea (b = -2.85 gm/cm2 per cups/day, SE = 1.56), and caffeinated cola (b = -14.0 gm/cm2 per cans/day, SE = 5.1), but not for decaffeinated coffee or decaffeinated cola [corrected]. [ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452902 TI - Menstrual cycle characteristics and the risk of endometriosis. AB - The present study utilized a case-control design to assess the relation between menstrual cycle factors and risk of endometriosis in women age 19-45 years. From a gynecologic specialty clinic in Western New York in 1987, we identified 104 laparoscopically confirmed cases of endometriosis. We used two control groups: (1) 100 friend controls (friends of cases), and (2) 98 medical controls (patients from the same medical practice with conditions other than endometriosis). Controls were frequency matched to cases by age. Because crude odds ratios (ORs), stratified by age (< 30 vs > or = 30 years), revealed effect modification by age, we performed all analyses by age group. We used logistic regression to calculate ORs and 95% confidence intervals (CIs), controlling for pregnancy, religion, and body mass index. Among women under age 30, using friend controls, we observed elevated risks for menstrual flow > or = 6 days per month (OR = 2.5, 95% CI = 1.1 5.9), heavy flow (OR = 2.5, 95% CI = 1.1-6.3), severe cramps (OR = 2.5, 95% CI = 1.2-6.0), increasing symptoms (OR = 6.6, 95% CI = 2.6-16.5), and tampon use > or = 14 years (OR = 3.6, 95% CI = 1.04-13.5). Risks were also elevated for women age 30 and over, but not to the same degree as among younger women.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452903 TI - Possible role of asthma in the risk of preterm labor and delivery. AB - We assessed the relation between maternal respiratory problems and preterm labor and delivery in a cohort of 3,891 women who delivered a singleton livebirth. Study participants were asked about their medical history in the 12 months before conception; women who reported a history of asthma had a higher risk of preterm labor [relative risk (RR) estimate = 2.33, 95% confidence interval (CI) = 1.03 5.26]. Asthmatic women also had an increased risk of preterm delivery (RR = 1.77, 95% CI = 0.60-5.24). Maternal respiratory problems during pregnancy were also associated with an increased risk of both inhibited preterm labor (RR = 2.14, 95% CI = 1.25-3.66) and preterm delivery (RR = 2.03, 95% CI = 1.08-3.82). Birthweight appeared to be unrelated to maternal history of asthma. Logistic regression models that adjusted for potential confounders did not appreciably alter the results. The adjusted odds ratio (OR) estimate for the odds of preterm labor in asthmatics relative to nonasthmatics is 2.42 (95% CI = 0.90-6.54); the analogous OR estimate for those with respiratory problems during pregnancy is 2.16 (95% CI = 1.14-4.10). The adjusted OR estimate for the odds of preterm delivery in asthmatics is 1.78 (95% CI = 0.53-6.02); for those with respiratory problems during pregnancy, the corresponding estimate is 2.00 (95% CI = 0.92-4.13). PMID- 8452904 TI - Self-reported use of pharmaceuticals and primary ovulatory infertility. AB - Over 1.5 billion prescriptions were filled by pharmacies in 1990, but little information exists on the effect that pharmaceutical agents have on female reproductive capacity. As part of a case-control study of risk factors for primary ovulatory infertility, we examined self-reported use of several prescription and nonprescription medications in 597 women with ovulatory infertility and 3,833 controls admitted for delivery at seven hospitals. Only women reporting use of a drug for at least 6 months, beginning before the onset of infertility in cases and before conception in controls, were considered exposed. An elevated risk of ovulatory infertility was found for women who ever used thyroid preparations [relative risk (RR) = 2.3, 95% confidence interval (CI) = 1.5-3.5] or antidepressants (RR = 2.9, 95% CI = 0.9-8.3), although the latter estimate was based on only five cases who reported having taken antidepressants. Current users of tranquilizers and ever-users for more than 2 years were also at greater risk of infertility than never-users (RR = 3.2, 95% CI = 1.1-8.5 and RR = 2.9, 95% CI = 0.8-11, respectively). Women who used asthma medication before age 21 had more than a twofold increase in risk of ovulatory infertility (RR = 2.5, 95% CI = 1.0-5.9). PMID- 8452905 TI - Data on prior pesticide use collected from self- and proxy respondents. AB - Proxy respondents have often been used in case-control studies of cancer and pesticides. To evaluate the effect of exposure misclassification, we compared data collected during 1981-1983 from participants interviewed for a case-control study of leukemia and non-Hodgkin's lymphoma with data collected during 1990-1991 from proxy respondents for participants who died or became incompetent since the initial interview (328 self-proxy pairs). As questions increased in detail, agreement percentages decreased. Agreement percentages were highest for demographic and general farming information (averages = 88-90%) and lowest for specific pesticide use (averages = 68-74%). Generally, odds ratios calculated from proxy respondent data were less than those from self-respondent data; however, several exceptions occurred. The findings indicate that pesticide data provided by proxy respondents will not necessarily result in the same estimate of risk and/or lead to the same conclusions as data provided by self-respondents. PMID- 8452906 TI - Black-white differences in idiopathic dilated cardiomyopathy: the Washington DC dilated Cardiomyopathy Study. AB - We conducted an epidemiologic study to examine the extent to which differences in purported risk factors account for black-white differences in risk of idiopathic dilated cardiomyopathy. We examined associations with race and other factors by comparing newly diagnosed cases (N = 122), ascertained from five Washington DC area hospitals, with neighborhood controls (N = 234) identified using a random digit dialing technique. We matched the cases and controls on sex and 5-year age intervals and analyzed the data using conditional logistic regression methods. We found that blacks were at increased risk for idiopathic dilated cardiomyopathy (relative odds = 2.6, 95% confidence interval = 1.6-4.3). The increased risk for blacks could not be explained by income, educational attainment, alcohol consumption, cigarette smoking, or history of hypertension, obesity, diabetes, or asthma. We also observed a possible interactive effect between black race and hypertension. PMID- 8452907 TI - The association of blood lead and blood pressure in population surveys. AB - Several reports from large population surveys have indicated that blood lead is positively related to blood pressure. We assessed this relation in 1,703 men (median blood lead = 83 micrograms per liter) and 1,661 women (median blood lead = 60 micrograms per liter), age 28 to 67 years, who participated in the first follow-up examination of the MONICA Augsburg cohort study in 1987-1988. Crude analyses confirmed a strong, positive association of blood lead concentrations with systolic and diastolic blood pressure. We identified age, body mass index, hematocrit, and alcohol consumption as the quantitatively most important confounders of this association. Adjustment for these variables, in particular for hematocrit and alcohol consumption, considerably reduced the magnitude of the blood lead effect on blood pressure. There were no indications for marked nonlinearity or threshold effects. After control of confounders, a difference of 100 micrograms per liter in blood lead levels, corresponding to rather extreme positions in the lower and upper end of the population blood lead distribution, related to estimated blood pressure increases of less than 3 mmHg. The appropriateness of treating hematocrit and alcohol consumption as confounders of the blood lead-blood pressure relation is discussed on the basis of current pathophysiologic concepts. We conclude that hematocrit should always be taken into account as a relevant confounder. On the other hand, the interrelation of alcohol consumption, blood lead, and blood pressure is presently not clearly understood; that is, its appropriate analytic handling cannot be determined. The consequences of these considerations on estimates of the blood lead effect on blood pressure may be both over- and underestimations. PMID- 8452908 TI - Normal or affected controls in case-control studies of congenital malformations and other birth defects: reporting bias issues. PMID- 8452909 TI - Exact stratification of person-years. PMID- 8452910 TI - A variation on a confidence interval theme. PMID- 8452911 TI - Misclassified sarcomas and confounded dioxin exposure. PMID- 8452912 TI - Determining the hazards of workplace chemicals. PMID- 8452914 TI - Product versus process. PMID- 8452913 TI - Exposure to butadiene and lymphatic and hematopoietic cancer. AB - Several follow-up studies have assessed lymphatic and hematopoietic cancer (LHC) among workers with potential exposure to 1,3-butadiene. These investigations of the styrene-butadiene rubber and butadiene manufacturing industries include 17,448 subjects with an average of 22 years of follow-up. When the results of the studies are combined, the total number of observed leukemia deaths is 36, compared with 34.2 expected. The standardized mortality ratio is 1.05, with a 95% confidence interval of 0.74-1.46. These null data are compatible with, at most, a weak positive association of butadiene with leukemia. There is little evidence of an association with other forms of LHC among styrene-butadiene rubber workers (55 observed/50.1 expected deaths). Only one study has evaluated directly the relation between estimates of butadiene exposure and leukemia, and this investigation reports a positive association. The result, however, cannot be interpreted as causal, because there is no satisfactory explanation for the marked discrepancy between this case-control study and a null follow-up study based on the same subjects. Overall, the epidemiologic evidence does not provide persuasive evidence that butadiene exposure causes LHC. PMID- 8452915 TI - Issues related to informed consent. AB - With advances in technology has come the promise for improved patient care. However, new and aggressive treatments can carry unexpected and unpredictable risks. Informed consent--a relatively recent concept--ensures that the patient is provided with ample information to make decisions about treatment. PMID- 8452916 TI - Characteristics and prevention of wound infection. AB - This article provides an overview of bacterial wound infection. It examines definitions of infection, types and concentrations of bacteria in wounds at different stages of healing, and the significance of osteomyelitis and sepsis in deep, necrotic ulcers. It also describes the culturing of wounds and examines the use of topical antimicrobials, debridement, irrigation, and occlusive dressings. Factors in surgical wound infection and infection control are examined. Finally, systemic factors are summarized. PMID- 8452918 TI - Sexual health promotion. PMID- 8452917 TI - Ileoanal reservoirs: construction and management. AB - The operative technique of ileal pouch-anal anastomosis is described, with specific attention to preoperative and postoperative counseling and ET nursing management of patients. This review is based on our experience with nearly 1400 ileal pouch-anal anastomosis operations at the Mayo Clinic since 1981. PMID- 8452919 TI - Development and implementation of a nursing skin care protocol. AB - More hospitals are using skin ulcer protocols to standardize care for the purpose of enhancing skin ulcer healing and reducing costs. This article outlines the role of the ET nurse in facilitating the development of a nursing protocol specific to an institution's needs. It outlines development of a monitoring tool to assess compliance and discusses the impact such a process had on the nursing and medical staffs in one community teaching hospital. PMID- 8452920 TI - Behavioral management strategies for urinary incontinence. AB - Behavioral interventions are recommended by Agency for Health Care Policy and Research Clinical Guideline as the first line of treatment for most types of urinary incontinence. This article defines and briefly describes the six behavioral treatment techniques and discusses the research base for the efficacy of each type of intervention. Caveats and needed research are also presented. PMID- 8452921 TI - Studies of adhesion of lymphocytic cells: implications for sexual transmission of human immunodeficiency virus. AB - Considerable evidence suggests that sexual transmission of human immunodeficiency virus (HIV) is mediated via mononuclear cells that can infect epithelia of the genital tract. We describe here an in vitro model that can be used to examine the mechanism of cell-to-cell transmission of this virus. We have employed the system to identify agents that may be effective in a vaginal formulation to prevent HIV transmission via sexual contact. We have previously shown that chronically HIV infected mononucleocytes can infect CD4-negative epithelial monolayers in the following manner: adhesion, via multiple microvilli, of HIV-infected mononucleocyte-derived cells to epithelial monolayers activates rapid virion secretion. Virions are then shed from the attached surface of the infected lymphocyte into a partially enclosed, microvilli-laden space between the cells. The shedding results in uptake of the virus and epithelial cell infection as demonstrated by ultrastructural examination and in vitro virological techniques. In this report, we present evidence from time-lapse films that HIV-infected lymphocytes adhere to the epithelium for a few minutes and then shift position to another site on the epithelium. As a result, one infected lymphocyte appears to be able to sequentially infected several cells of the epithelial monolayer. Using a fluorescence-based cell-cell adhesion assay to examine the effect of seminal fluid and a variety of chemical compounds on lymphocyte-to-epithelial adherence, we found that seminal fluid significantly increases the number of lymphocytes adhering to epithelia. This suggests that semen can serve as an effective medium for cell-cell transmission of HIV. On the other hand, sulfated polysaccharides and glutathione effectively inhibit cell-cell adhesion. Since the cell-cell adhesion step is critical to epithelial cell infection by HIV, these results suggest that anti-cell adhesion compounds may be effective in a vaginal formulation to reduce the probability of HIV infection. PMID- 8452922 TI - An estrogen-dependent glycoprotein is synthesized and released from the oviduct in a temporal- and region-specific manner during early pregnancy in the ewe. AB - Administration of estradiol-17 beta (E) to ovariectomized (ovx) sheep results in the synthesis and release of an M(r) 90,000-92,000 glycoprotein into the oviductal lumen and into culture medium of ampullar explants (Biol Reprod 1992; 47:889-902). The objective of this study was to determine when and from what region of the oviduct the M(r) 90,000-92,000 glycoprotein is synthesized and released during early pregnancy. Estrous ewes were bred to intact rams of known fertility, and oviducts were obtained at estrus (Day 0) and at Days 1.5, 2, 3, 4, 6, and 16 of pregnancy. Pregnancy was verified by the presence of a fertilized egg or developing conceptus and a functional corpus luteum. Oviductal secretions were collected by flushing oviducts with saline and by explant culture. The oviductal fimbria, ampulla, and isthmus were individually cultured (24 h) in the presence of 3H-leucine (3H-leu) or 3H-glucosamine (3H-glcN). The presence of the M(r) 90,000-92,000 glycoprotein in oviductal flushings and culture medium was determined by fluorography and Western blotting. The M(r) 90,000-92,000 protein was present in SDS gels and blots of oviductal flushings from animals through Days 4-6 of pregnancy, but not in flushings from Day 16 pregnant animals or from ovx, untreated animals. This protein was present in 3H-leu- and 3H-glcN-labeled culture medium of the oviductal ampulla (Days 0, 1.5, 2, 3, 4, 6, and 16) and fimbria (Days 0, 1.5, 2, 3, and 4) during early pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452923 TI - Uterine cellular changes in 2',5'-oligoadenylate synthetase during the bovine estrous cycle and early pregnancy. AB - The signal for maternal recognition of pregnancy in cattle is bovine trophoblast protein-1 (bTP-1), a Type I trophoblast interferon. One of the many functions of interferons is the induction of the 2',5'-oligoadenylate (2-5[A]) system, which is involved in cell division and selective degradation of mRNA. The present study focused on the cellular changes of 2-5(A) synthetase in bovine endometrium during the estrous cycle and early pregnancy. Ability of recombinant bTP-1 to stimulate activity of the enzyme in uterine cells throughout the estrous cycle was also evaluated in vitro. Surface epithelium, glandular epithelium, and stroma were enzymatically separated in cows on Day 5, 10, 15, or 18 postestrus and on Day 15 or 18 of pregnancy. Cell samples were lysed and frozen for determination of the endogenous cellular content of 2-5(A) synthetase. Additional cells obtained during the estrous cycle were cultured and treated with increasing doses of recombinant bovine interferon alpha (rbIFN-alpha) or recombinant bTP-1 (rbTP-1). During the estrous cycle, 2-5(A) synthetase was greatest on Day 5 and declined approximately 10-fold by Day 15 (p < 0.01). Cellular content of 2-5(A) synthetase was similar among all three endometrial cell types. In the gravid horn of pregnant animals, presence of a conceptus significantly increased (p < 0.01) 2 5(A) synthetase in all endometrial cell types compared to levels on Days 15 and 18 of the estrous cycle. On Day 18, levels of 2-5(A) synthetase were 30-fold greater (p < 0.01) in epithelium (surface and glandular) from pregnant cows compared to that from cyclic cows.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452924 TI - Puberty in the male chimpanzee: time-related variations in circulating inhibin. AB - Circulating immunoreactive inhibin concentrations were determined in male chimpanzees (n = 12) during a 36-mo period starting 18 mo before the onset of pubertal testicular growth (Po). Serum levels of inhibin started to increase, together with LH and testosterone, 6 mo before a rise in FSH and Po. Before Po, inhibin was not related to gonadotropins but was related to testosterone levels (r = 0.263; p < 0.005; R2 = 7%). After Po, inhibin remained related to testosterone (r = 0.289, p < 0.01) but became inversely related to gonadotropins; FSH was the best predictor (r = -0.382, p < 0.0005; R2 = 30%) of this relationship. During the progressive rise in circulating inhibin, FSH increased and plateaued during 9 mo, then dropped to prepubertal levels. These findings suggest that a specific closed-loop negative feedback system for the secretion of FSH by inhibin is not functional before the onset of puberty in the chimpanzee. This feedback system seems to fully operate several months after the LH rise and may be related to the complete maturation of both Sertoli cells and spermatogenesis. PMID- 8452925 TI - Isolation of ovine luteal cell subpopulations by flow cytometry. AB - Differences in the characteristics of small and large luteal cells, as reported by various laboratories, may be due to species diversity and/or methodological differences in cell preparation. To evaluate whether the method of cell separation affects the properties of luteal cell subpopulations, we sorted and characterized sheep luteal cells by flow cytometry via methods previously used to investigate luteal cell subtypes from the macaque corpus luteum. Corpora lutea were obtained from superovulated ewes on Day 10 after hCG injection and enzymatically dissociated. Dispersed cells were shipped overnight on ice from the University of Arizona to the Oregon Regional Primate Research Center. Viability of cells upon arrival was > or = 80%. When dispersed cells were analyzed by flow cytometry based on forward and 90 degrees light scatter, three distinct subpopulations (P1, P2, P3) were identified. In P1, 35.5 +/- 2.1% of cells, most (97.0 +/- 0.6%; n = 3) of which were 15-22 microns in diameter, stained positive (+) for 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity. The remainder of P1 cells were 3 beta-HSD negative and < or = 22 microns. The size distribution of P2 was similar to that of P1, but P2 contained more (53.3 +/- 4.2%; n = 4) 3 beta-HSD (+) cells. P3 consisted mostly (88.5 +/- 4.6%; n = 3) of 3 beta-HSD (+) cells > 25 microns in diameter. Cell subpopulations were incubated (n = 6) at 37 degrees C for 3 h with or without hCG (0.1-100 ng/ml), prostaglandin E2 (PGE2; 500 ng/ml), or dibutyryl (db)-cAMP (5 mM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452926 TI - Evidence for a role of the liver in the luteotropic action of prolactin in rats. AB - Recent studies indicate that the liver may participate in growth-promoting and lactogenic activity of prolactin (PRL). Accordingly, our study was designed to determine whether the liver participates in the luteotropic activity of the hormone in rats. Normally cycling Long-Evans rats received infusions of solvent or 50 micrograms ovine (o) PRL per day into either the external jugular vein (EJV) or the hepatic portal vein (HPV) via osmotic minipumps. The modes of delivery were continuous, 2 pulses of 8 h each per day (2-8), or 4 pulses of 2 h each per day (4-2). Observation of daily vaginal smears was used to classify rats as either cyclic or predominantly diestrus (PD). In a second study, rats fitted with osmotic minipumps received oPRL or vehicle as above, and serial blood samples were obtained for measurement of serum oPRL and rat (r) PRL concentrations. Estrous cycles of normal length were observed in 9 of 11 rats (82%) receiving solvent infusions. All 8 animals receiving continuous oPRL infusions were classified as PD, regardless of site of infusion. In addition, in 4 of 5 (80%) HPV-infused and 5 of 6 (83%) EJV-infused rats on the 2-8 pulse schedule, the smear patterns were classified as PD. However, when rats received 4 2 EJV, 9 of 13 animals (69%) were classified as cyclic, whereas 9 of 11 rats (82%) were classified as PD when oPRL was similarly pulsed into the HPV. Differences in serum concentrations of oPRL between oPRL-treated and vehicle infused rats were significant only for continuously infused animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452927 TI - Cycle of the seminiferous epithelium in the Djungarian hamster (Phodopus sungorus sungorus). AB - In this study, spermatogenesis in the adult Djungarian hamster is described. Undifferentiated spermatogonia topographically arranged as Asingle (A(s)), Apaired (Apr), and Aaligned (Aal) spermatogonia were observed, as were six generations of differentiating spermatogonia (A1, A2, A3, intermediate, B1, and B2). The differentiating spermatogonia divided at regular intervals during the cycle of the seminiferous epithelium. Mitosis of these cells was observed at the transition from stage IX to stage X (mitosis of A1 into A2 spermatogonia), at the transition from stage XII to stage I, at the transition from stage II to stage III, at the transition from stage IV to stage V, at the end of stage VI, and at approximately the middle of stage VII. Cellular associations in the cycle of the seminiferous epithelium are described. The seminiferous epithelium was divided into 12 stages, based upon the developmental steps in spermiogenesis, and the frequency of these stages was determined. The duration of the cycle of the seminiferous epithelium, determined by [3H]thymidine incorporation, was shown to be 7.90 +/- 0.01 (mean +/- SEM) days. PMID- 8452928 TI - Immunohistochemical localization of spermatid nuclear transition protein 2 in the testes of rats and mice. AB - Transition protein 2 (TP2) of the rat was isolated by differential precipitation with trichloroacetic acid, chromatography over Bio-Rex 70, and preparative gel electrophoresis. A polyclonal rabbit antiserum was raised that did not cross react with unrelated acid-soluble proteins from liver or testes. The antiserum was used to identify TP2-related proteins obtained from testes of mice, hamsters, guinea pigs, rabbits, and boars by Western blotting. Immunohistochemical techniques were used to localize TP2 in paraffin-embedded testis sections from mice and rats. In both species, TP2 was first detected in spermatids that had essentially completed the morphological change from a round to an elongate nucleus and that were undergoing chromosomal condensation (spermatids of step 13 in rat and step 12 in mouse). TP2 was retained in spermatid nuclei until early step 16 in the rat and step 14 in the mouse. Serial sections of rat testis exposed separately to antisera to TP1 and TP2 showed that the great majority of labeled tubules were reactive to both antisera. However, in occasional tubules, TP1 reactivity was retained in relatively late spermatids that were negative for TP2. Thus both TP1 and TP2 appear in the nucleus essentially simultaneously, in association with the beginning of chromatin condensation and at a point well after much of the nuclear shaping has occurred. PMID- 8452929 TI - The fetal circadian pacemaker is not involved in the timing of birth in hamsters. AB - The role of the fetal circadian pacemaker in the timing of birth was examined in Syrian hamsters (Mesocricetus auratus). Two groups of pregnant hamsters with lesions of the suprachiasmatic nucleus received daily intraperitoneal injections of melatonin (25 micrograms) on Days 9-15 of gestation. One group was injected with melatonin in the evening and the other in the morning. After the last set of injections, the animals were observed every hour until they gave birth. The timing of birth was not significantly different in the two groups, indicating that it was not affected by the melatonin injections. In contrast, the average phases of the pups' activity rhythms at weaning were significantly different in the two groups; this difference, approximately 10 h, indicated that the prenatal melatonin injections set the phases of the pups' circadian pacemakers. These results suggest that the fetal pacemaker is not involved in the timing of birth, since the pacemaker could be set to different phases without affecting this timing. In a separate study, time of birth and length of gestation were measured for heterozygous tau mutant pups, which express a circadian rhythm with a period of approximately 22 h. The results were compared with similar measurements obtained from a previous study of wild-type pups that express a circadian rhythm with a period of approximately 24 h. In both cases, the pups had been born to wild-type mothers. The timing of birth was similar in the two groups, indicating that the tau mutation does not influence the length of gestation or the time of day when birth occurs. PMID- 8452930 TI - Induction of endogenous insulin-like growth factor-I secretion alters the hypothalamic-pituitary-testicular function in growth hormone-deficient adult dwarf mice. AB - To evaluate the influence of growth hormone (GH) on hypothalamic-pituitary testicular function, GH-deficient adult male Ames dwarf mice were treated (s.c.) twice daily for 8 days with either vehicle or bovine GH (25 micrograms/injection/mouse). Normal male siblings treated with vehicle served as controls. Two in vivo experiments were conducted. In experiment 1, on Day 8, mice were treated (i.p.) with either saline or LHRH (1 ng/g b.w.) in saline. Fifteen minutes later, blood was obtained via heart puncture to assess plasma insulin like growth factor-I (IGF-I), LH, and testosterone (T) levels by RIAs. In experiment 2, on Day 7, mice were bilaterally castrated and received injections of either oil or T propionate (1 microgram/g b.w.) in oil. Eighteen to twenty hours later, blood was obtained as in experiment 1, and plasma IGF-I and LH levels were determined. In addition to these in vivo experiments, testicular androstenedione and T responses to hCG stimulation in vitro were evaluated. Administration of GH to dwarf mice increased (p < 0.001) plasma IGF-I levels, whereas IGF-I was not detectable in control dwarf mice. Plasma IGF-I concentrations were higher in normal mice than in treated dwarf mice. Basal LH levels were lower (p < 0.025) in dwarf mice than those in normal mice. In dwarf mice, GH treatment increased (p < 0.001) plasma LH levels. The effect of LHRH on LH secretion was increased (p < 0.001) in dwarf mice pretreated with GH, but this LH response was lower than in normal siblings that received vehicle only.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452931 TI - Epidermal growth factor and transforming growth factor-beta modulation of follicle-stimulating hormone-induced deoxyribonucleic acid synthesis in hamster preantral and early antral follicles. AB - The interactions of epidermal growth factor (EGF) and transforming growth factor beta (TGF-beta) in modulating FSH-induced follicular DNA synthesis were studied in isolated intact preantral (stages 1-6) and early antral (stage 7) ovarian follicles from adult hamsters. Follicles were exposed in vitro for 24 h to FSH (100 ng), EGF (50 ng), TGF-beta 1 (1-10 ng), or TGF-beta 2 (1-10 ng), either alone or in combination. The rate of DNA synthesis was assessed by measuring the incorporation of [3H]thymidine into follicular DNA. Both EGF and FSH significantly stimulated follicular DNA synthesis compared with that in controls. Both isoforms of TGF-beta significantly increased follicular [3H]thymidine incorporation in a dose-dependent manner; the effect was greater for small preantral follicles, such as those of stages 1-4. Interestingly, TGF-beta significantly inhibited EGF-induced follicular DNA synthesis, but the rates of DNA synthesis for most of the stages were still higher than that of the control follicles. Specificity of the TGF-beta action on follicular DNA synthesis was evident from the ability of isoform-specific anti-TGF-beta antibodies to neutralize the effect. These antibodies also reversed the TGF-beta inhibition of EGF-induced DNA synthesis. Surprisingly, although TGF-beta attenuated EGF-induced DNA synthesis, it synergized with FSH to stimulate follicular DNA synthesis. Interestingly, FSH-induced DNA synthesis remained unaffected by the anti-TGF-beta antibodies, indicating that TGF-beta may not mediate FSH action on follicular DNA synthesis. These studies suggest that a critical interaction of EGF and TGF-beta modulates granulosa cell proliferation during folliculogenesis in the hamster.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452932 TI - Transforming growth factor-beta potentiation of follicle-stimulating hormone induced deoxyribonucleic acid synthesis in hamster preantral follicles is mediated by a latent induction of epidermal growth factor. AB - The mechanisms of transforming growth factor-beta (TGF-beta) potentiation of FSH action on follicular DNA synthesis in the hamster were investigated by use of TGF beta (beta 1 and beta 2) and a potent epidermal growth factor (EGF)-specific polyclonal antibody. Preantral follicles at stages 1-6 and early antral follicles at stage 7 were enzymatically and mechanically isolated from adult golden hamsters on proestrus. Follicles were incubated in Dulbecco's modified Eagle's medium with ITS+ (6.25 micrograms insulin, 6.25 micrograms transferrin, 6.25 micrograms selenium, 1.25 mg BSA, and 5.35 micrograms linoleic acid/ml) hydrocortisone, and 1 microCi/ml [3H]thymidine. Follicles were exposed for 24 h to FSH (100 ng/ml), TGF-beta 1, and TGF-beta 2 (1 and 10 ng/ml), EGF antibody (50 microliters/ml), and TGF-alpha (50 ng/ml) under various experimental conditions. Both TGF-beta 1 and TGF-beta 2 significantly potentiated FSH-induced follicular DNA synthesis; however, the effect was drastically attenuated by EGF antibody. EGF antibody also inhibited FSH-induced follicular [3H]thymidine incorporation. TGF-beta 2 potentiation of FSH action was also significantly inhibited by a second dose of TGF-beta 2 when added 6 h after the beginning of culture; however, follicles at different stages responded differently to the second dose of TGF beta 2. For example, when the second dose of TGF-beta 2 was added 14 h after the first dose, only the large preantral follicles at stages 4-6 were affected. Interestingly, the second dose of TGF-beta 2 also inhibited TGF-beta 2-induced DNA synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452933 TI - Differential gene expression in fetal mouse germ cells. AB - We have constructed cDNA libraries representing transcripts from purified populations of germ cells and of somatic cells, isolated from fetal mouse gonads at 12.5 days postcoitum (dpc). We have used these libraries to study differential gene expression in fetal germ cells on the basis of differential representation of specific cDNAs in each library. We show that in addition to expression of housekeeping genes at expected levels, four genes responsible for germ cell specific phenotypes are expressed at significantly different levels in germ cells and surrounding somatic cells. These include tissue-nonspecific alkaline phosphatase (tnAP), transcription factor Oct-3/4, the c-kit proto-oncogene, and DNA methyltransferase (Mt). The significance of these results is discussed in the context of events contributing to early development of germ cells. It is concluded that fetal germ cells appear to retain a pattern of gene expression resembling that in early pluripotent embryonic cells, and that this may be important for the maintenance of genetic totipotency. PMID- 8452934 TI - Uterine space affects placental protein secretion in swine. AB - The effect of altering uterine space available to developing conceptuses on placental and endometrial protein secretion and endometrial 3H-thymidine incorporation on Days 25 and 35 of gestation was tested. Gilts bred at estrus (Day 0) were laparotomized on Day 4, and the uterine horn ipsilateral to the ovary with the most ovulations was ligated midway between the uterine tip and uterine bifurcation to create a crowded and a roomy uterine environment. On Day 25 (n = 7) or 35 (n = 6), gilts were killed and the reproductive tract was dissected from each. Each placenta and fetus was weighed, and a sample of endometrium adjacent to each placenta was collected. Within each uterine environment, tissues (500 mg) from the heaviest and lightest (by weight) placentae and adjacent endometrial tissue were cultured for 24 h at 37 degrees C in 15 ml Minimal Essential Medium having 0.1 times the normal amount of leucine plus 50 microCi 3H-leucine. Aliquots (2 ml) of dialyzed medium were subjected to two-dimensional PAGE and fluorography to examine proteins with molecular weight ranges of approximately M(r) 20,000-130,000, and a further aliquot was subjected to SDS-PAGE to examine low molecular weight proteins (M(r) 2000-20,000). In addition, endometrium (200 mg in duplicate) adjacent to the heaviest and lightest placentae within each uterine environment was incubated for 4 h in 5 ml MEM plus 1 microCi 3H-thymidine to measure DNA synthesis. After culture, 3H-thymidine incorporation and total DNA were determined. Fetal survival in the crowded uterine environment decreased (p < 0.05) on Day 35 compared to Day 25. On both days, the heaviest and lightest placentae from the crowded uterine environment weighed less (p < 0.01) than the heaviest and lightest placentae from the roomy uterine environment. The fetuses associated with the heaviest and lightest placentae from the crowded uterine environment also weighed less (p < 0.05) than fetuses associated with the heaviest and lightest placentae from the roomy uterine environment. Nondialyzable radioactivity in medium per gram of tissue cultured from placental cultures decreased (p < 0.05) and from endometrial culture increased (p < 0.05) between Days 25 and 35. Placental secretion of a protein with M(r) 46,000, pI 5, decreased between Days 25 and 35. Endometrial secretion of three proteins (M(r) 35,000, pI 6.2; M(r) 25,000, pI 4.9; and M(r) 14,000, pI unknown) increased, and secretion of three other proteins (M(r) 24,000, pI 6.5 doublet; M(r) 22,000, pI 7.5, and M(r) 7000, pI unknown) decreased from Day 25 to Day 35 of pregnancy.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8452935 TI - Hypophysectomy of the cyclic mouse. I. Effects on folliculogenesis, oocyte growth, and follicle-stimulating hormone and human chorionic gonadotropin receptors. AB - The effects of hypophysectomy (HX) on folliculogenesis, oocyte growth, and ovarian FSH and LH receptors were examined by histology, topical autoradiography, and in vitro incubation of isolated follicles with [3H]thymidine. At random stages of the estrous cycle, mice were HX (Day 0), and they were killed from 0 to 20 days thereafter. Four days after HX, the number of preantral (stages 1-3) and antral (stages 4-5) follicles per ovary was reduced by 40% to 60% compared to Day 0 values, and stage 6 (large preovulatory) follicles had vanished. By Day 20 after HX, the numbers of follicles at stages 1, 2, and 4 were comparable to Day 4 values, whereas stage 3 and 5 follicles were still further diminished to 30% and 15% of Day 0 values, respectively. The number of atretic follicles from Days 0 to 20 after HX did not differ for follicles of stages 3-5, and stage 1 and 2 follicles were all healthy. However, oocyte growth was not coordinated with follicular growth after HX; the oocytes of stage 2-4 follicles were significantly larger than Day 0 oocytes. The enlarged oocytes appeared normal as judged by light and electron microscopy. DNA synthesis for stage 1-3 follicles declined significantly from Days 4 to 20 compared with Day 0 values, but did not change for stage 4 and 5 follicles, since atretic follicles at these stages were still labeled by [3H]thymidine and this was rare for Day 0 follicles. Topical autoradiography for [125I]-labeled FSH and hCG showed that follicular receptors for both hormones declined by Day 4 of HX and remained undetectable thereafter, except for trace amounts of [125I]-hCG binding in the interstitium. The decrease in follicular DNA synthesis and the greater diameter of oocytes in preantral follicles after HX suggest that longer transit times are required for one stage to progress to the next because of the anhormonal environment of the growing follicle. These results provide concrete evidence that pituitary gonadotropins are essential in the mouse for initiation, proliferation, and differentiation of all stages of growing follicles. PMID- 8452936 TI - Hypophysectomy of the cyclic mouse. II. Effects of follicle-stimulating hormone (FSH) and luteinizing hormone on folliculogenesis, FSH and human chorionic gonadotropin receptors, and steroidogenesis. AB - This study was designed to determine the effects of FSH and LH on ovarian follicular development in adult hypophysectomized (HX) mice. Twelve days after HX, the animals received s.c. injections of ovine FSH (oFSH; 4 micrograms/day) or oFSH (4 micrograms/day) plus ovine LH (oLH; 2 micrograms/day) twice a day for 1 to 4 days. After 4 days of treatment with FSH alone, the number of preantral follicles (stages 1-3) increased significantly compared to that in HX controls and reached cyclic numbers; however, incorporation of [3H]thymidine into these preantral follicles as compared to HX controls did not increase. The number of healthy antral follicles (stages 4-5) and incorporation of [3H]thymidine into stage 5 follicles started to increase after only 1 day of treatment with FSH, and the number of atretic follicles concomitantly decreased. Treatment with both FSH and LH for 1 to 4 days increased the number of healthy follicles and restored DNA synthesis at all stages (1-5) to normal levels. Two days of replacement with FSH or FSH plus LH was required for follicles to attain preovulatory size (stage 6). FSH alone induced FSH and hCG receptors in granulosa cells, but without the induction of thecal LH/hCG receptors; FSH induced production of progesterone and androstenedione by stage 6 follicles, but not estradiol (E2) accumulation in the incubation medium or in the serum. Combined FSH and LH induced hCG receptors in the theca and interstitium, and also restored follicular E2 production to proestrous values. LH alone increased only the number of stage 2-3 follicles. Unexpectedly, LH alone also induced thecal hCG receptors as well as FSH receptors in granulosa cells of preantral and antral follicles. The present results demonstrate that FSH is essential for follicular growth at all stages and for prevention of atretic antral follicles. Both FSH and LH are necessary for regulation of follicular development and differentiation from the earliest preantral to preovulatory stages. PMID- 8452937 TI - Normal fertilization and development of frozen-thawed mouse oocytes: protective action of certain macromolecules. AB - Freezing and thawing of mouse oocytes causes changes in the zona pellucida that reduce fertilization. The fertilization and development of oocytes were studied after freezing and thawing in media containing 1.5 M dimethylsulfoxide (DMSO) and various macromolecular supplements: BSA (Fraction V and crystalline), fetal calf serum (FCS), and polyvinyl alcohol (PVA). In conditions under which the fertilization rate of oocytes frozen in medium containing BSA was reduced, oocytes frozen in medium containing FCS were fertilized at rates approaching those of nonfrozen controls. Significantly fewer oocytes were fertilized after freezing in the presence of PVA than oocytes frozen in medium containing BSA or FCS. Fertilization of oocytes frozen in the presence of PVA was significantly increased when serum was included in the medium during dilution of the cryoprotectant. The in vitro and in vivo development of embryos obtained from frozen-thawed oocytes was independent of the macromolecular supplement used in the freezing medium and was similar to that of nonfrozen control oocytes. The results show that given the appropriate conditions for freezing and thawing, cryopreserved mouse oocytes undergo fertilization and development at rates similar to those for nonfrozen controls. PMID- 8452938 TI - Functional and morphological features of spermatozoa microaspirated from the epididymal regions of cynomolgus monkeys (Macaca fascicularis). AB - In most species examined to date, spermatozoa mature during transit through the epididymis to become functionally competent to swim progressively, fertilize oocytes, and produce viable offspring. In the studies presented here, the status of spermatozoa obtained from the regions of the epididymis of the cynomolgus monkey (Macaca fascicularis) was examined. Epididymal fluid was collected by microaspiration from the caput, corpus, and cauda regions. The spermatozoa obtained were evaluated for morphology, motion parameters, and tight zona pellucida binding and were compared to spermatozoa collected by electroejaculation. Epididymal and ejaculated sperm differed morphologically only in the location of the cytoplasmic droplet. Motile sperm recovered by swim-up procedure exhibited a significantly higher proportion of sperm with more distal cytoplasmic droplets than the original aspirated samples (p < 0.02). Poor duration of movement was most noticeable for corpus spermatozoa, and to a lesser degree for cauda spermatozoa, when the motion parameters of velocity, linearity, and amplitude of the lateral head were examined. Zona pellucida binding was decreased only for sperm microaspirated from the caput region; sperm obtained from the corpus and cauda regions bound comparably to those collected via electroejaculation. These results suggest that by the time cynomolgus sperm reach the corpus region of the epididymis, they are functionally competent for tight zona binding. However, these nonhuman primate sperm may not complete the metabolic changes requisite for sustained sperm motility until reaching the most distal regions of the epididymis. PMID- 8452939 TI - Localization of secretory, membrane-associated and cytoskeletal proteins in rat testis using an improved immunocytochemical protocol that employs polyester wax. AB - Immunocytochemistry is a compromise between maintaining antigenicity and preserving tissue morphology. In the testis, successful immunostaining results at the level of resolution provided by the light microscope have been obtained through use of either frozen or paraffin sections, although both techniques are fraught with limitations. With freezing, tissue preservation is not optimum, whereas with paraffin embedding, antigenicity is often destroyed. These limitations are not trivial and have led to numerous ambiguous results in the literature. In the present study we wish to report the results of immunocytochemical localization of various proteins in testis fixed by perfusion with Bouin's fluid and embedded in polyester wax, a ribboning embedding medium for histology. The advantages of this medium are that it does not require clearing of tissues in xylene solvents before embedding and that unlike paraffin, it liquifies at 38 degrees C. Because of these two properties, the polyester was appears to adequately maintain antigenicity as compared to that observed in frozen sections, yet because it is a ribboning wax, it preserves detailed structure as well as paraffin does. Proteins that were immunolocalized included cytoskeletal proteins (tubulin, actin, vinculin, vimentin) and cell-specific markers: 1) androgen-binding protein (ABP) for Sertoli cells; 2) peripheral type benzodiazepine receptor (PBR) for Leydig cells; and 3) nuclear lamins for germ cells. Biotin-streptavidin peroxidase immunocytochemistry was employed to determine the specific distribution of the various proteins, and both rabbit antisera and mouse monoclonal antibodies were used with equal success. In addition, fluorochrome-labeled second antibodies combined with confocal microscopy were used to examine the disposition of the antigens in the testis. Results revealed maintenance of antigenicity and morphology far superior to that obtained with paraffin and frozen sections, respectively, they also showed that within the seminiferous epithelium, germ cell or Sertoli cell-specific proteins were unambiguously immunolocalized to their respective cells. Specific observations made possible through use of this protocol suggest that neither tubulin or vimentin immunostaining patterns in Sertoli cells are altered during the cycle of the seminiferous epithelium. Similarly, ABP staining appeared constant throughout the cycle. Further, we wish to report that anti-PBR is a specific probe for Leydig cells in vivo and that an anti-nuclear lamin antibody appears to serve as a specific probe for spermatogonia and pachytene spermatocytes, but that the commercially available anti-smooth muscle alpha-actin monoclonal antibody immunostains both the myoid and lymphatic endothelial cells forming the peritubular cells layer of the seminiferous tubule.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8452940 TI - Factors affecting fertility in the postpartum cow: role of the oocyte and follicle in conception rate. AB - Four experiments were designed to examine the contribution of the oocyte or the follicular, oviductal, or early uterine environments to low fertility associated with the first ovulation postpartum. At 17-25 days postpartum in experiments 1, 2, and 3, suckled beef cows were assigned at random to receive 6 mg norgestomet, via ear-implant, for 9 days (NOR) or to serve as controls (CON). Calves were weaned from all cows 7 days after assignment to treatment in order to induce estrus, an LH surge, ovulation, and subsequent formation of CL. As cows were detected to be in estrus, they were bred first by natural service and 12 h later by artificial insemination. In experiment 1, on Day 3 after estrus, the oviduct ipsilateral to the side of ovulation was removed and flushed for recovery of an embryo or oocyte. Rates of recovery (86%), fertilization (68%), and development of fertilized oocytes to the 4- to 8-cell stage (100%) did not differ between CON and NOR cows. In experiment 2, uteri were flushed nonsurgically on Day 6 after estrus. Rates of recovery of embryos from the uterus were similar between CON (86%) and NOR (71%) cows. In experiment 3, one half of the cows in each group (CON and NOR) were fed melengestrol acetate (MGA) beginning on Day 4 after estrus and continuing until Day 35. The remaining cows in each group served as controls. Treatment with NOR increased (p < 0.05) the proportion of cows that maintained pregnancy until Day 35 (9/22) as compared to controls (0/18).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452941 TI - Effects of individual and combined treatment with prostaglandins E2 and F2 alpha on progesterone secretion by ovine luteal cells supplemented with homologous serum lipoproteins in vitro. AB - Prostaglandin F2 alpha (PGF2 alpha) is a potent luteolysin, whereas prostaglandin E2 (PGE2) is generally luteotropic in vivo. To establish a model system for investigations of the mechanisms involved in these actions, we examined the effects of individual and combined treatment with PGE2 and PGF2 alpha on basal and ovine LH-stimulated progesterone secretion during long-term incubations conducted with and without supplemental homologous low-density lipoprotein (LDL) as substrate. Effects of both PGF2 and PGF2 alpha were concentration- and time dependent and were further influenced by the presence of LDL and/or LH in medium. Neither of the prostaglandins exerted any significant effect before 48 h in culture, but distinctly different patterns of response to PGE2 and PGF2 alpha emerged thereafter. Low, but not high, concentrations of PGE2 increased progesterone secretion in the absence of LH, whereas PGF2 alpha (alone and in combination with PGE2) inhibited progesterone production in all medium formulations. The transcriptional inhibitor actinomycin effectively blocked the actions of PGF2 alpha, but had no effect on response to LH or PGE2. These data demonstrate that both the putative luteotropic actions of PGE2 and the potent, luteolytic effects of PGF2 alpha in vivo can be reproduced in long-term cultures of ovine luteal cells in vitro, and they suggest that the mechanism of PGF2 alpha induced luteolysis may involve new protein synthesis. PMID- 8452942 TI - Correlations among three measures of puberty in mice and relationships with estradiol concentration and ovulation. AB - Correlations among ages and weights at vaginal opening (AVO, WVO), positive vaginal smear (AVE, WVE), and copulatory plug (AVP, WVP) were determined using 623 mice. Two additional experiments were conducted to determine association of each with serum concentrations of estradiol and incidence of ovulation. Female mice were weaned at 21 days and 24 days of age were assigned randomly to mate with males. Mice were checked daily to determine AVO, AVE, and AVP. Mice were weighted weekly and WVO, WVE, and WVP were obtained by interpolation. Genetic correlations among ages and weights were small and mainly negative. Phenotypic correlations were small to moderate and mainly positive. Genetic correlations among the three measures of age and among the three measures of weight were moderate to high and positive; respective phenotypic correlations were somewhat smaller. In experiment 2, mice were checked daily for the three reproductive measures and bled at vaginal opening (n = 23), positive smear (n = 18), or copulatory plug (n = 19). Serum was assayed for estradiol via radioimmunoassay. No differences were found among the three indicators (p = 0.34). In experiment 3, mice were randomly assigned to be killed after detection of vaginal opening, positive smear, or copulatory plug. Oviducts were removed and flushed with saline to determine presence of ova. A greater (p < 0.05) proportion of mice had ovulated when killed after detection of copulatory plug (20/22) than after positive smear (4/27), and the proportion was greater after positive smear than after vaginal opening (0/14).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452943 TI - Characterization of laminin receptor messenger ribonucleic acid and protein expression in mouse spermatogenic cells. AB - A cDNA proposed to encode the mouse laminin receptor (MLR) was isolated from a mouse round spermatid expression library. The cDNA contained complete coding and 3' untranslated regions but was missing the first 42 bases from the 5' untranslated region. Northern blot analysis using a 3' EcoRI fragment of the cDNA identified a 1.2-kb transcript in mouse testes and all somatic tissues tested. Additional transcripts of 1.3 and 0.9 kb were present in round spermatids isolated from mouse testes. Northern blots using ribonuclease (RNase) H-treated poly(A)+ RNA indicated that the difference in the size of 1.3-kb round spermatid transcripts and 1.2-kb transcripts was due to differing poly(A)+ tail lengths. The 0.9-kb round spermatid transcript hybridized to all but the 5' end of the 1.2 kb MLR cDNA, suggesting that an alternate start site is used or that transcript processing occurs in these cells. Immunoblot analysis identified proteins in spermatogenic cells corresponding to the 67-70-kDa MLR and its 43-kDa precursor. In addition, ligand binding studies and affinity chromatography procedures indicated that spermatogenic cell proteins of these sizes bind laminin. However, spermatocytes and spermatids are spatially isolated from laminin in the testes, and MLR may have other functions in these cells. PMID- 8452944 TI - Gonadotrope responsiveness in orchidectomized sheep. II. Effect of gonadotropin releasing hormone amplitude shift during continuous infusion of estradiol. AB - Gonadotropin secretion during continuous infusion of estradiol (E2; 5 micrograms/h, i.v.) and pulsatile delivery of GnRH was assessed in orchidectomized sheep (wethers). Wethers received 200 ng GnRH per hourly pulse during the first 12 h of E2 infusion. During the final 36 h of infusion, animals (n = 6/group) received 0, 200, 400, 800, or 1600 ng GnRH/h pulse. Amplitude shift to 1600 ng GnRH/h pulse induced preovulatory surge-like secretion of LH in animals receiving concurrent E2 infusion. In the absence of E2, the same change in GnRH amplitude did not significantly affect serum concentrations of LH. Full expression of the GnRH-induced surge of LH in wethers required prior exposure to E2, but was not dependent on pretreatment with low-amplitude GnRH stimulus. In a companion experiment, anterior pituitary tissue was collected from E2-treated wethers 0, 3, 6, 12, or 24 h after initiation of episodic GnRH delivery (1600 ng/h pulse). Treatment with E2 induced a 5-fold increase in GnRH receptor concentration. The tissue concentration of GnRH receptor was depressed (p < 0.05) within 6 h of initiation of high-amplitude GnRH stimulation and remained depressed for the duration of GnRH delivery. Tissue stores of LH were increased (P < 0.05) by E2 and reduced (p < 0.05) after 3 h of high-amplitude GnRH stimulation. In contrast, tissue stores of FSH were reduced (p < 0.05) by both E2 alone and E2 with concurrent high-amplitude GnRH stimulation. The concentration of mRNA for the FSH beta subunit, but not for the alpha or LH beta subunits, was reduced (p < 0.05) by E2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8452945 TI - Coccidioidomycosis: new aspects of epidemiology and therapy. PMID- 8452946 TI - Arguments against the chemoprophylactic use of zidovudine following occupational exposure to the human immunodeficiency virus. AB - Following the paradigm of the hospitals of the National Institutes of Health and the University of California at San Francisco, many medical facilities have instituted a policy of administering zidovudine to health care workers after exposure to blood potentially contaminated with the human immunodeficiency virus. There is no clinical evidence proving the efficacy of such chemoprophylaxis. Toxic effects associated with zidovudine are usual and at times severe. The institutional administration of zidovudine to anyone other than individuals infected with the human immunodeficiency virus should be discontinued except under the auspices of a randomized, placebo-controlled trial. PMID- 8452947 TI - Malaria in splenectomized patients: report of four cases and review. AB - The spleen plays a central role in host defense against malaria in animals. Its role in human malaria is less well established. The spleen may contribute to protection against human malaria by mediating humoral or cellular immune responses or by clearing both rheologically and immunologically altered host erythrocytes. This report describes Plasmodium falciparum and Plasmodium vivax infections that occurred after splenectomy in one nonimmune and three partially immune Thai adults. The clinical course was uncomplicated for all four patients, and parasite clearance was delayed only in the nonimmune patient. In three patients with falciparum malaria, humoral and cellular immune responses to blood stage antigens during the acute infection and convalescence were similar to those of individuals whose spleens were intact. These findings suggest that the spleen may not be essential for the processes leading to parasite clearance in partially immune, splenectomized patients. Further studies on the course of malarial infections in splenectomized patients are crucial for clarifying the role of the spleen in host defense against human malaria. PMID- 8452948 TI - Diagnosis of Helicobacter pylori infection by means of a polymerase chain reaction assay for gastric juice aspirates. AB - A polymerase chain reaction (PCR) assay for Helicobacter pylori was developed with use of primer sequences from the ureA structural gene coding for the small subunit of urease. The PCR amplification was 100% specific for H. pylori in tests with 40 stock isolates of this species and with 30 control organisms, including two species of urease-producing Helicobacter. Thirty-four dyspeptic patients were evaluated by culture and histologic assessment of antral biopsy samples as well as by PCR of gastric juice aspirates. In 26 of the 34 patients, infection with H. pylori was diagnosed by culture and histology. PCR correctly identified 25 of these 26 patients. All eight patients with negative cultures and histologic findings also had negative PCR results. In this group of patients, therefore, PCR had a sensitivity of 96% and a specificity of 100%. Thus PCR of gastric juice aspirates can be used to diagnose H. pylori infection. This information is important since gastric juice can be aspirated through a nasogastric tube without gastroduodenoscopy. In addition, since clinical samples can be collected at one institution and mailed to a laboratory at another without compromising the outcome of the test, diagnostic PCR is accessible even to those clinicians at whose institutions the technology required for the procedure is not available. PMID- 8452949 TI - Outbreak of Pseudomonas aeruginosa infections in a surgical intensive care unit: probable transmission via hands of a health care worker. AB - Pseudomonas aeruginosa was isolated from nine patients (16.2 isolations/1,000 patient-days) in a surgical intensive care unit during an outbreak in November 1990; this rate of isolation was three times higher than that noted previously on this unit. Three patients were infected with the same strain, as defined by identical serotypes, pyocin types, and contour-clamped homogeneous electric field (CHEF) electrophoresis patterns of digested genomic DNA. The hands of 80 health care workers were cultured, and a strain of P. aeruginosa identical to that infecting the three patients was isolated from the hands of a nurse providing care to all three. Environmental surfaces, medical devices, and ward stock supplies were cultured; none of these cultures yielded this strain. No clusters of infection with this strain or other strains of P. aeruginosa were observed after compliance with hand-washing and universal precautions was reemphasized. Thus this outbreak was linked to the carriage of P. aeruginosa on the hands of a health care worker. It could not be determined definitively whether this carriage was the source of the cluster or a consequence of it. However, the geographic and temporal clustering of carriage with an outbreak due to a strain of an apparently identical molecular type underlines the importance of routine hand washing between contacts with different patients. PMID- 8452950 TI - Agrobacterium radiobacter: a recently recognized opportunistic pathogen. AB - Over the past decade, an increasing number of infections due to Agrobacterium radiobacter have been reported. Observation of three cases of bacteremia due to this organism prompted a review of the English-language literature. Nineteen cases of significant disease have previously been reported. In more than one-half of the cases, bacteremia was the primary manifestation, often associated with the presence of an intravascular catheter. Other clinical syndromes (peritonitis, urinary tract infection, and endocarditis) have been described. Infection is strongly related to the presence of plastic foreign material, and effective treatment often requires removal of the device. Because antimicrobial sensitivity is variable, treatment must be based on sensitivity data for the individual isolate. PMID- 8452951 TI - Fatal encephalitis caused by concomitant infection with tick-borne encephalitis virus and Borrelia burgdorferi. AB - We describe a 38-year-old farmer from the southwestern archipelago of Finland where both tick-borne encephalitis (TBE) virus and Borrelia burgdorferi are endemic. He presented with fever and headache, developed severe meningoencephalitis in 3 days, and, after 1 month, died without regaining consciousness. High titers of IgG and IgM antibodies to TBE virus were present in both serum and CSF. Serology for Borrelia was negative. Autopsy revealed necrotizing encephalitis and myelitis with involvement of the dorsal root ganglion. With use of polymerase chain reaction tests, segments of two separate genes of B. burgdorferi were amplified from the patient's CSF. This case demonstrates that the possibility of dual infection should be considered for patients residing in geographic areas where Ixodes ticks may carry both the TBE virus and B. burgdorferi. We believe that the most severe damage in this case was caused by TBE virus rather than by B. burgdorferi. Nevertheless, the coinfection might have contributed to the fatal outcome that has not been previously observed in Finnish patients with TBE. PMID- 8452952 TI - Sinusitis due to Pseudomonas aeruginosa in patients with human immunodeficiency virus infection. AB - Community-acquired sinusitis due to Pseudomonas aeruginosa developed in four patients with advanced human immunodeficiency virus (HIV) infection who had no local predisposing factors or neutropenia. Two persons were bacteremic. Combination antibiotic therapy and surgical drainage were necessary for adequate treatment. Ciprofloxacin-resistant strains were isolated possibly because of the chronic use of the drug as part of a treatment regimen for disseminated infection with Mycobacterium avium complex. Physicians treating patients with HIV infection must have an increased index of suspicion for P. aeruginosa as a causative agent of sinusitis. PMID- 8452953 TI - Environmental mycobacterial peritonitis complicating peritoneal dialysis: three cases and review. AB - Mycobacterial peritonitis is rare among patients undergoing peritoneal dialysis. It is usually caused by group IV environmental mycobacteria. We report three such cases and review the literature on this subject. Negative results in routine bacterial cultures and persistent peritonitis may be the only clues indicating the presence of mycobacterial infection. The lack of specific symptoms and signs as well as inadequate culture techniques may delay diagnosis. Multiple cultures of centrifuged dialysis fluid may be required for isolation of the organism. Peritoneal biopsy may yield additional diagnostic information. Management frequently entails removal of the dialysis catheter in addition to antimicrobial therapy. Significant morbidity may ensue if treatment is delayed. Amikacin--with or without another antibiotic--provides adequate coverage. PMID- 8452954 TI - Necrotizing pancreatitis and multisystem organ failure associated with toxoplasmosis in a patient with AIDS. AB - Extraneural manifestations of toxoplasmosis often are not recognized antemortem in patients with AIDS. We describe a patient who was seropositive for human immunodeficiency virus and presented with lethargy, abdominal tenderness, rapidly progressive ventilatory failure, rhabdomyolysis, myoglobinuria, and disseminated intravascular coagulation. Although the diagnosis of pancreatitis was not considered while the patient was alive, an autopsy demonstrated pancreatic necrosis associated with toxoplasmal cysts. No other infection was evident. This case suggests that Toxoplasma gondii can cause severe pancreatitis in patients with AIDS. PMID- 8452955 TI - Staphylococcal meningitis can present as an abscess of a single lateral ventricle. AB - Ventricular obstruction and hydrocephalus are recognized complications of neurosurgical procedures and meningitis that has been previously treated. The confinement of bacterial meningitis solely to a lateral ventricle in an otherwise healthy individual, however, is rare. I describe a case in which a ventricular abscess occurred as the presenting manifestation of staphylococcal meningitis in a man who had no history of head trauma or neurosurgery. PMID- 8452956 TI - Prosthetic hip infection and bacteremia due to Campylobacter jejuni in a patient with AIDS. AB - Campylobacter jejuni is a common enteric pathogen in healthy individuals and in patients with AIDS. It usually causes a self-limited diarrheal illness with fever and abdominal pain. We report what we believe is a unique case of C. jejuni osteomyelitis in a 60-year-old man who had hemophilia A, AIDS, and a hip prosthesis. He presented to the hospital with a 4-day history of fever and diarrhea and a 1-day history of hip pain. Findings on plain films and a bone scan were suggestive of osteomyelitis in the proximal femur. Cultures of blood and a hip aspirate yielded C. jejuni. PMID- 8452957 TI - Infection due to Klebsiella rhinoscleromatis in two patients infected with human immunodeficiency virus. AB - Two cases of rhinoscleroma in patients infected with the human immunodeficiency virus (HIV) who had stayed in an area of endemic Klebsiella rhinoscleromatis are reported. One of the patients presented with oropharyngeal lesions, an unusual clinical picture. Both patients suffered from a major cellular immune deficiency. The importance of Klebsiella rhinoscleromatis infection in AIDS-related oropharyngeal pathology and the possible treatment of such infection in HIV positive patients are not yet clearly established. PMID- 8452958 TI - Acute gastroenteritis caused by Hafnia alvei in children. PMID- 8452959 TI - Group A streptococcal sepsis secondary to acute salpingitis. PMID- 8452960 TI - Pulmonary infection due to Exophiala jeanselmei: successful treatment with ketoconazole. PMID- 8452962 TI - Induction and assessment of immunity at enteromucosal surfaces in humans: implications for vaccine development. AB - It is now almost axiomatic that vaccines against enteric infections must be able to stimulate the gut lymphoid tissue to be efficacious and that this goal is usually better achieved by administering immunogens orally rather than parenterally. On the basis of the notion of a common mucosal immunologic system that provides immune reactivity not only at the site of antigen deposition but also at remote mucosal sites, there is much interest in developing oral vaccines against infections in the respiratory and urogenital tracts. Recent studies indicate that oral administration of small amounts of protein antigens that are chemically or genetically linked to intestinal binding carrier molecules (such as the B subunit of cholera toxin) can evoke vigorous mucosal and extramucosal immune responses. The apparent compartmentalization of systemic and mucosal immune responses may explain not only why parenteral vaccines are just partly effective in protecting against mucosal pathogens but also why currently employed immunoanalytical methods do not provide accurate information regarding mucosal immune status. Following the developments of oral vaccines against infections due to Vibrio cholerae and enterotoxigenic Escherichia coli, two archetypes of enteropathogens, we have devoted extensive efforts to gaining insight into the humoral and cellular events involved in the development of protective immunity in the human intestinal tract. We have developed preparative and analytical methods for studying vaccine-induced intestinal and extraintestinal immune responses in humans. These include techniques for collecting intestinal fluid and lymphoid cells as well as procedures to quantitate secretory antibodies and lymphokines secreted by activated intestinal immunocytes. These developments should serve the dual purpose of facilitating analyses of human mucosal immune responses in general and assessing the immunogenicity of enteric vaccines in particular. PMID- 8452961 TI - Septic arthritis due to Corynebacterium diphtheriae. PMID- 8452964 TI - Host factors in resistance to infectious diarrhea. Osaka, Japan, 14-15 September 1990. Papers presented at the symposium. PMID- 8452963 TI - Diarrhea in helminthic infections. AB - Enteric helminths are among the most prevalent parasites of humankind, yet only scanty information exists about their effects on the gastrointestinal tract of their hosts. Specifically, there is little agreement on which worms definitely cause diarrhea. The available evidence suggests that five helminthic parasites are associated with human diarrheal disease: Trichinella spiralis (early phases of infection), Trichuris trichiura, Strongyloides stercoralis, Capillaria philippinensis, and Schistosoma (particularly Schistosoma mansoni). All these parasites have an invasive phase during which adult worms, their eggs, or their larvae establish intimate contact with the host's intestinal mucosa and elicit strong local inflammatory responses resulting in various structural and functional alterations of the gut. In contrast, strictly intraluminal worms do not seem to interfere with their hosts' intestinal structure and function to a degree sufficient to cause diarrhea. PMID- 8452965 TI - Biochemical and genetic basis for the ETS (enterotoxin sensitivity) phenotype in mice. AB - Evidence has been accumulating that humans are genetically predisposed to cholera gravis. Using the sealed adult mouse model, we found that certain inbred mice were also hypersensitive to cholera toxin (CT). Such mice were designated ETS+ (enterotoxin sensitive), and the trait was linked to the K end of the mouse H-2 histocompatibility complex. Cells isolated from ETS+ mice bound more CT and accumulated more cyclic adenosine monophosphate (cAMP) after intoxication. Analysis of ETS+ cells showed that they express lesser amounts of the non-GM1 gangliosides that block or compete for relevant CT binding sites in ETS- cells. Conversion of ETS- non-GM1 gangliosides to GM1 with neuraminidase increased CT binding and cAMP responses. Reconstitution of nonreactive ganglioside-deficient cells with ETS+ or ETS- gangliosides caused them to bind CT like the original ETS+ or ETS- cells. Ganglioside expression genes known to map to the same H-2 linked region as the ETS phenotype seem to be involved in controlling murine susceptibility to CT. PMID- 8452966 TI - Genetic studies of human and murine giardiasis. AB - Wide variation has been observed in the natural history of human and murine giardiasis, which could be due to factors associated with the parasite or with the host. In humans, prolonged infections with Giardia duodenalis have been associated with hypogammaglobulinemia, protein-calorie malnutrition, and prior gastrectomy. The duration of infection or severity of symptoms may also be influenced by the humoral immune response and by other factors such as ABO blood group and HLA antigen type. Elimination of Giardia muris is impaired in hypothymic mice, B-cell-deficient mice expressing the xid gene, and in mice deficient in mast cells. Prolonged infections also occur following depletion of helper/inducer T cells and suppression of antibody production with antisera to IgM. However, quantitative or qualitative defects in immune function do not appear to account for prolonged cyst excretion in C3H/He, C3H/HeJ, and A/J mice. The defect in these strains is influenced by several genes and may involve intermediate or late stages of macrophage activation leading to impaired elimination of the parasite. PMID- 8452967 TI - [Studies of efficacy and tolerance in elderly patients]. PMID- 8452968 TI - [Observations on the effect of the circadian rhythm on the appearance of a myocardial infarct]. PMID- 8452969 TI - [Kaposi's sarcoma and portal hypertension in human immunodeficiency virus infection]. PMID- 8452971 TI - [Cutaneous metastases: a rare finding?]. PMID- 8452970 TI - [Inflammatory arthropathy and celiac disease]. PMID- 8452972 TI - [A urinary outbreak of Acinetobacter baumanii in a spinal cord injury unit]. AB - From January 1990 to April 1992, 114 urinary strains of Acinetobacter baumanii were isolated in 57 patients with traumatic spinal cord [correction of medular] injury. The strains were characterized by having all of them the same biochemical identification, except for citrate, maltose and tryptophan-desaminase. Until December 1990, (5 strains) were resistant to all antibiotics, except to tobramicine, amikacine, cotrimoxazol and imipenem (6.3%, 33.9%, 26.7% and 0% of resistances, respectively); since January 1991, (99 strains) became resistant to all of them, except to imipenem. 39.5% of AB were isolated in pure cultures, 46% of them with pyuria. Between February 1991 and January 1992, we observed the highest number of affected patients, although without seasonal predominance. We observed as well a higher incidence among males (46 males, 11 females). 80% of them carried a permanent probe. Only 6 patients presented clinical signs directly related to AB. The environmental study could not demonstrate any source of contagion or transmission mechanism. PMID- 8452973 TI - [The pulmonary toxicity of amiodarone in our hospital: apropos 8 cases]. AB - We present the most relevant data of a series of 8 cases of PTA coming from our environment. We highlight the onset of PTA with low doses of amiodarone (equal or lower than 400 mg/day), the affectation of only aged patients (range 63-77 years) and always, except in one case, during the first five years of treatment with amiodarone. Dyspnea was the most frequent symptom. The definition of PTA is mainly clinical-radiological and it has no biochemical, radiological or functional unique characteristics, determining the need for a careful differential diagnosis. The prognosis was excellent when the administration of amiodarone was stopped and, in some cases, steroids were added. PMID- 8452974 TI - [The pattern of the sensitivity of Aeromonas spp. that produce extraintestinal infections]. AB - We studied the sensibility to several antimicrobics of aeromonas strains isolated in extraintestinal infections during a period of five years, in order to establish which could be the best empirical therapy in these processes. Twenty two strains of A. hydrophila were evaluated, was isolated (8 from hemocultures, 6 from wound exudate, 2 from abscess aspirate, 2 from peritoneal fluid and 1 from urine, pleural fluid, bile and catheter). The identification was made using the GNI card System (Vitek System) and other tests. The sensibility was assessed using the GNS-BH and GNS-BI card System (Vitek), which allows to know the clinical category and CMI value in microgram/ml. All the strains presented some resistance to antibiotics. 77.8% of the strains were resistant to more than one antibiotic and 64.9%, to more than two antibiotics. We detected 21.7% strains resistant to 4 drugs. The most frequent resistance association was ampicillin, cephoxitine, cephazoline, cephalotine, with or without amoxicillin and clavulanic acid. All the strains were sensible to cephamandol, cephuroxime, cephtriaxone, cephtazidime, cephotaxime, thicarciline, aztreonam, azlociline, mezlociline, piperaciline, gentamycin, amikacine, chloranphenicol and ciprofloxacine. All the strains were resistant to ampicillin; 60.9% of the strains were sensible to the association amoxicillin and clavulonic acid. In conclusion, the treatment of extraintestinal infections does not differs basically from the treatment of the infections caused by Gram-negative bacillus. There are a broad range of effective antibiotics: aminoglycosides (gentamycin, tobramycin, amikacine), piperacyline, cephalosporines (cephuroxime, cephotaxime, cephtazidime and cephtriaxone), chloranphenicol, penemas, monobactanes of fluorquinolone. PMID- 8452975 TI - [Involuntary weight loss]. AB - Involuntary weight loss is a clinical situation with unknown incidence, significance and prognosis. We present a retrospective study of 68 patients hospitalized due to involuntary weight loss. The most frequent individual cause was neoplasia; however, globally, non-neoplastic causes were most frequent. None of the symptoms was significantly associated to the diagnosis of a neoplastic or non-neoplastic disease. The mean age of the patients with neoplasia (71.36 +/- 17.19) differed from the mean age of the patients without neoplasia (63.39 +/- 17.19 years) (p < 0.05). The patients with neoplastic and infectious diseases needed a higher number of analysis than the other patients, being the most valuable data the presence of anemia, cholestasis and determination of thyroid hormones. The most useful evaluations were clinical and endoscopical assessments, thoracic radiography and abdominal echography. PMID- 8452977 TI - [Tracheobronchial amyloidosis: a report of a new case]. AB - Tracheobronchial amyloidosis is the most frequent manifestation of pulmonary amyloidosis. We present the case of a patient who initially presented pneumonia with atelectasis in the upper right lobe (URL) and in whom the presence of nodular bodies in all the bronchial tree was detected with bronchoscopy, with almost complete obstruction of the URL bronchus, identified as amyloid AL. Therapy with laser photoresection was effective, with almost complete resolution of the obstruction. PMID- 8452976 TI - [Common variable immunodeficiency and polyarthritis: a case report]. AB - We describe a man with common variable immunodeficiency and polyarthritis. He had suffered several infections, including septic arthritis. For this reason we commenced treatment with antibiotics without obtaining a good response. Three weeks' later, and after knowing that the results of all the cultures were negative, we discontinued the antibiotic therapy and started treatment with indomethacin. A dramatic response was rapidly observed. We feel that an arthritis in a patient with a history of previous infections should alert us to the diagnostic possibility of primary antibody deficiency. PMID- 8452978 TI - [Acute human immunodeficiency virus infection associated with facial diplegia]. AB - We describe the case of a 21-year-old parenterally drug-addict man, who presented an acute and self-limited disease, temporarily associated to seroconversion against the human immunodeficiency virus. During his evolution, the patient developed aseptic meningitis and facial diplegia. Two lymphatic ganglions were histopathologically and sequentially studied during the third and sixth week of the disease, showing an intense follicular depletion in the first sample, which reverted towards a pattern of follicular hyperplasia in the second one. PMID- 8452980 TI - [Diagnostic problems in nosocomial pneumonias]. PMID- 8452979 TI - [Mediastinal leiomyosarcoma]. AB - Primary mediastinal leiomyosarcomas are malignant sarcomas with unknown etiology not deriving from the smooth muscle fiber of the esophagus, trachea or main vessels. Very few cases have been reported in the literature and, although they are clinically unspecific, their histology is unique. The case described here is a 66-year-old woman with a leiomyosarcoma localized at the medium and posterior mediastinum, clinically presented as a mediastinal emergency. PMID- 8452981 TI - [Helicobacter pylori and the treatment of gastric ulcer. Reflections and uncertainties]. AB - The authors examine the relationship between Helicobacter pylori and gastric ulcer therapy, analyzing both the data suggesting that eradication of the organism renders the gastric mucosa less susceptible to development of gastric ulcer and the substantial body of evidence to the contrary. They review the results reported in clinical trials with colloidal bismuth subcitrate, antimicrobial agents (furazolidone), and combinations of antiulcer and antimicrobial agents (H2-antagonist + cefixime, H2-antagonist + metronidazole). Also analyzed is the relationship between Helicobacter pylori eradication and ulcer recurrence; only one study is available on this aspect, and the limited evidence it provides in favour of a prophylactic effect of eradication therapy is not entirely convincing. The authors conclude that there is no reasonable case for the dogmatic assumption that eradication of Helicobacter pylori facilitates either acute healing or long-term prophylaxis of gastric ulcer, though certain subgroups of gastric ulcer patients may benefit from eradication therapy. PMID- 8452982 TI - [Cutaneous metastases as a form of presentation of a retroperitoneal leiomyosarcoma]. PMID- 8452983 TI - [Multiple myeloma, macrocytosis and pancytopenia]. PMID- 8452984 TI - [The CREST syndrome and Hashimoto's thyroiditis, apropos a case seen in our primary care center]. PMID- 8452985 TI - [Self-care in primary health care: a pending issue]. PMID- 8452986 TI - [Wide QRS tachyarrhythmia]. PMID- 8452987 TI - [Treatment of hypotension in patients with psychiatric symptoms: basis for a controversy]. PMID- 8452988 TI - [Pancreatitis following vaccination against measles, mumps, and rubella in a young adult]. PMID- 8452989 TI - [Monostotic Paget's disease. Detection of a case in primary care]. PMID- 8452990 TI - [Organic disease and psychogenic disease: differential diagnosis in primary care]. PMID- 8452991 TI - [Geriatric homes: a pending course]. PMID- 8452992 TI - [Quality and variability. European consensus in primary care?]. PMID- 8452993 TI - [Nurse care in primary health care: diagnosis and follow-up of health problems]. AB - OBJECTIVE: To evaluate the results of nursing staff putting into practice a number of health prevention and promotion schemes, with particular emphasis on the follow-up of the health problems detected. DESIGN: A crossover study. SITE. A care unit of the Sant Just Desvern Primary Care team. PATIENTS: A total of 136 people were seen. 58% were men and 42% women. Their average age was 39.30 +/- 16. MAIN MEASUREMENTS AND RESULTS: The risk factors found were: tobacco, alcohol, exercise, arterial tension, cholesterol, weight, dental and oral hygiene, gynecological check-ups, self-examination of breasts and anti-tetanus, German measles and flu vaccinations. Using the clinical records it was found that 42.64% were smokers; 1.58% were alcoholics and 20.63% consumed an excessive amount of alcohol; 47.58% were sedentary; 17.09% were diagnosed with dyslipaemia; and 1.58% with hypertension. After the intervention, 18.96% gave up smoking and 14.28% of excessive drinkers managed to stop. 76.47% of women advised to attend the gynaecologist did so. 89.61% of patients completed the series of anti-tetanus vaccinations. CONCLUSIONS: The favorable response of the population to a periodic health check-up should be emphasised. The changes in life-style brought about after the detection and subsequent follow-up of health problems was extremely positive. PMID- 8452994 TI - [Detection of prescription errors in drug dispensing: incidence and typology]. AB - OBJECTIVE: Description and quantification of the types of prescribing errors during dispensing activities at community pharmacies. DESIGN: Descriptive transversal study carry out along four weekly periods. SITE. Eighteen pharmacies from six of the spanish autonomous regions dispensing prescription orders mainly issued by the National Health Service. PATIENTS AND OTHER TAKING PART: 37,321 prescriptions of specialties dispensed by the mentioned pharmacies along the four week period. MAIN MEASUREMENTS AND RESULTS: An unstructured questionnary was applied to all persons asking for one of the mentioned prescriptions. When an error was suspected, a second structured questionnary was applied by the pharmacist to the order bearer and the answers plus the information contents at the prescription form was collected on a data-sheet. Data were processed on a dBase and SPSS programs. Incidence detected error of 1.35%. Types of error classified into five categories. Study of the variability of error detection by week and by pharmacy. Analysis and comparison with references of the "order author" data and "prescriptor" data. CONCLUSIONS: Our global incidence of detected error was lower in relation with other studies. We found short differences by weeks and large by pharmacies. Inadequate definition of the drug was the most frequent type of error. The detection frequency of posology error was higher following the use of the new prescription order model. The number of orders from different prescriptor/author was larger in our study in relation to the notified by other studies. PMID- 8452995 TI - [Approximation to the detection of drug adverse reactions among doctors at the primary health care level]. AB - OBJECTIVE: To try to find the pattern of adverse reactions to drugs (ARD), as observed by Primary Care doctors, and the opinion of these on control of drugs. DESIGN: This was a descriptive, crossover study carried out by means of a postal questionnaire filled in by the interviewee. SITE. The Province of Cordoba. PARTICIPANTS: Primary Care doctors in the province of Cordoba. MAIN MEASUREMENTS AND RESULTS: 403 doctors (rate of reply: 31.6%) answered the questionnaire. The most commonly observed ARDs are those connected with digestive conditions (dyspepsia, 19.4%; diarrhea, 10.9%; nausea and vomiting, 10.4%), followed by dermatological complaints. 36.6% of doctors suspect at least one ARD a week. The therapeutic groups most frequently responsible are analgesic/antiinflammatory drugs, followed by antibiotics/chemotherapies. 49.7% were ignorant of the "Yellow Card" programme, although 86.6% showed a favorable attitude to being notified. CONCLUSIONS: The level of awareness of the possibility of ARD among the doctors polled is high. The "Yellow Card" programme is still little known. It is well worth circulating information, especially in view of Primary Care professionals' high level of motivation. PMID- 8452996 TI - [Approximation to the nutritional status with a nutrition survey in the health area]. AB - OBJECTIVE: As part of an overall diagnosis of health in our Area we carried out a study of nutritional habits and attitudes, with the aim of altering the negative aspects by health education. DESIGN: A descriptive study of a questionnaire filled in by a sample taken from the electoral roll in our Health Area. SITE. Tonepacheco Health Area (Murcia). PARTICIPANTS: 600 inhabitants. MAIN MEASUREMENTS AND RESULTS: 82.7% consumed milk products once or more a day. 66.3% ate meat, eggs and fish between one and three times a week. 74.8% consumed legumes, potatoes and dried fruits; 95.8% bread, rice and pasta; 77.7% biscuits, sweets and chocolates; and 71.2% consumed fats; the preceding all between one and three times a week. 44.2% ate green and root vegetables between 4 and 6 times a week. 89.4% are fruit once or more a day. 73.4% ate out of the house between 4 and 6 times a week. Of the 2.8% of children who drank alcoholic drinks, 66.3% did so habitually. CONCLUSIONS: We believe it is important to emphasise in health education the need for a balanced diet, with special attention being paid to enolic habits in children. PMID- 8452997 TI - [The rifampicin test in the diagnosis of Gilbert syndrome]. AB - OBJECTIVE: To show the effectiveness and feasibility of the Rifampicin test in diagnosing Gilbert's syndrome. DESIGN: A prospective, descriptive study. SITE. General Medical Service of the Navarra Hospital. PATIENTS: 17 patients with bilirubin levels on two or more occasions and 6 healthy patients without these data. Both in- and out-patients. MAIN MEASUREMENTS AND RESULTS: The Rifampicin test. Bilirubin levels were determined when fasting and one, two, three and four hours after taking 900 mg of Rifampicin (Rimactan). After the test, those patients who had Gilbert's disease presented bilirubin levels significantly higher than the healthy patients, who remained within normal levels. CONCLUSIONS: In the group studied, the Rifampicin test demonstrated its effectiveness in the diagnosis of suspected Gilbert's disease. It would therefore be possible to use this test in the Primary Care field. PMID- 8452998 TI - [Iconographic approximation to skin semiology]. PMID- 8453000 TI - [The evolution of research in primary care]. PMID- 8452999 TI - [Marketing in primary care: towards a new direction of the services]. PMID- 8453001 TI - [Can we decrease pharmacy costs?]. PMID- 8453002 TI - [Where does the terminal patient die?]. AB - OBJECTIVE: To determine whether patients terminally ill with gastric cancer die in hospital or at home and what the conditioning factors are. DESIGN: Descriptive, crossover and retrospective study. SITE. A province-wide study in Zaragoza province. PATIENTS: The sample consisted of 606 patients in Zaragoza province who had been diagnosed, between 1980 and 1989, as suffering gastric cancer and who later died of this condition. MEASUREMENTS AND MAIN RESULTS: The follow-up rate of the patients' evolution was 96%. Of these, 50.2% died in hospital and 46.2% at home. Average age was 67 +/- 10 years. 62% were men; 38% women. Average time of survival was 6 months. None of these factors nor the existence or otherwise of surgery affected the place of death. What was notable was that 42% of patients in urban areas died at home; whereas 66% did so in rural areas (p < 0.0001). CONCLUSIONS: Patients terminally ill with gastric cancer in Zaragoza province are just as likely to die at home as in hospital. In rural areas people are significantly more likely to die in their own homes. We believe these findings demonstrate the need to develop Primary Care programmes to alleviate terminal suffering. PMID- 8453004 TI - [A psychiatric morbidity study of the population attending the Basauri Health Center]. AB - OBJECTIVE: To calculate the probable prevalence of mental illness in our clinics and to evaluate how it is detected by Primary Care (PC) doctors. DESIGN: Crossover study in two parts. SITE. Basauri Health Centre (Vizcaya). PARTICIPANTS: A sample made up of patients who attended the clinic without prior appointment during ten days in February and Marc, 1990. MAIN MEASUREMENTS AND RESULTS: In the first part, 10 PC doctors distributed the GHQ-28 questionnaire to 500 patients. In the second part, qualified staff administered the standardised psychiatric interview (SPI) to a sub-sample. 41.55% were possible psychiatric cases (GHQ-28 > 6). 17.94% were diagnosed by the doctors (SD) as psychiatric cases. Prevalences adjusted to the SPI were 19% and 21% for the GHQ-28 and SD respectively. CONCLUSIONS: The GHQ-28 obtained high sensitivity (0.82%) and low specificity (60%), which characterises it as a good screening test, but a bad diagnostic method. The doctors obtained low sensitivity (0.29) and high specificity (89.7%); thus underdiagnosing mental illness, but being more accurate in their diagnoses. PMID- 8453003 TI - [A re-evaluation of the program for diabetes mellitus type 2. A proposal for quality indices]. AB - OBJECTIVE: To find out how accurate our records are and the state of health of the patients with diabetes mellitus type II (DM) in our Base Health Area (BHA) in Osona county (Barcelona), both before and after introducing a new procedure. DESIGN: Quality control study based on the medical records (PCMR) of DM patients. The evaluation took place between 1.1.90 and 31.12.90; and the re-evaluation between 1.1.91 and 31.12.91, after the DM procedure had been put in place as a corrective measure. PATIENTS: 198 patients: all of those suffering from DM type II. MAIN MEASUREMENTS AND RESULTS: 110 women and 88 men, with an average age of 65.4 +/- 11.9, were under study. We observed from the records of attendance that 94.4% were or had been smokers, whereas the question of the eye fundus was only mentioned in 36.8%. The introduction of a procedure has improved the records in almost every parameter. In 1991, 36.8% of the patients had normal-weight criteria, 33.3% had good biochemical control and 15.6% fulfilled both these criteria. CONCLUSIONS: Those tests which could be performed with few instruments were carried out much better than those which needed more complex technology or specialist support. Arising from this study, the authors propose four indicators of quality control: 1) Weight normality. 2) Annual plasmatic fructosamine. 3) Annual eye fundus check. 4) Annual proteinuria check. PMID- 8453005 TI - [The attitudes of physicians and nurses to the integration of mental health into primary care]. AB - OBJECTIVE: To establish the attitude of health staff at Health Centres to new Mental Health care plan. DESIGN: Crossover study, for which a simple random sample of 207 people was extracted. SITE. Seville's Primary Care network. PARTICIPANTS: Doctors and nurses from Health Centres in Sevilla. MAIN MEASUREMENTS AND RESULTS: A questionnaire of 22 items, grouped into the 5 thematic areas of the new plan, was designed to measure attitudes. The statistical treatment analysed the variables of: age, sex, profession, type of Health Centre, participation in health programmes and the relationship to the District Mental Health Team (DMHT), 55% of health workers scored positively overall in the questionnaire. Those belonging to urban Health Centres were more favorable than those in rural centres to the incorporation of mental health into Primary Care. Those under 35 were also more favorable. Looking at thematic areas, the least preferred was "Organisation", whereas all the other areas scored positively. CONCLUSIONS: Strategies for the introduction and organisation of the new mental health plan will have to be designed before it can be implemented in Health Centres. PMID- 8453006 TI - [Care for drug addicts in primary care]. AB - OBJECTIVE: 21 drug addicts' reasons for attending (RA) primary care clinics were studied. DESIGN: A six-month long prospective study. SITE: An attendance group, as in Insalud's traditional model, from an area of Madrid with a high level of drug use. PARTICIPANTS: Everybody known to be dependent on drugs and who could be followed up. 9 out of 21 drug addicts were HIV+. MEASUREMENTS AND MAIN RESULTS: Out of the 51 RA's established, the most common one was high temperature (27.4%), even when the HIV+ (37.5%) and HIV- (26.3%) groups were considered separately, though the number of consultations for high temperature was significantly higher (p < 0.01) among HIV+ patients. Other important RA's were those arising from drug abuse (efforts to give up; request for substitution therapy etc.) (25%). The total number of consultations with drug addicts represented 2.8% of the total number of consultations with the population as a whole during the same period of time. CONCLUSIONS: The high demand placed by drug addicts on the Primary Care network is confirmed by this study. High temperature and problems arising from drug abuse were the most common RA's. High temperature was the main RA both in HIV+ and HIV- patients. PMID- 8453007 TI - [Platelet antiaggregants: a review of their indications in primary care]. PMID- 8453008 TI - [The diagnosis and treatment of the most frequent menstrual changes in primary care (I)]. PMID- 8453009 TI - [The loss of the efficacy of captopril due to indomethacin]. PMID- 8453010 TI - [The treatment of arterial hypertension]. PMID- 8453011 TI - [A case of the massive ingestion of furosemide with suicidal intent]. PMID- 8453012 TI - [Oligoarthritis as the initial manifestation in human immunodeficiency virus infection]. PMID- 8453013 TI - [Food poisoning by Clostridium botulinum type II]. PMID- 8453014 TI - A quality control system involving peer review of abnormal cervical smears. AB - An internal quality control system which is used in the centralized cytology laboratory of a population-based cervical cancer screening programme in Florence is described. It includes a peer review procedure. Abnormal cervical smears are circulated among all the cytologists and a consensus on the final diagnosis is reached. This daily procedure is designed to evaluate the performance of each cytologist and of the laboratory as a whole but can also be considered a valuable training opportunity. During an 18-month period 1197 smears were reviewed by 15 readers using a reporting form with six main categories of reporting (from 'negative' to 'invasive carcinoma'), plus an 'unsatisfactory' category. Overall the concordance between the 15 cytologists, assessed using the kappa statistic (range 0.46-0.71; median 0.60), was good. The level of agreement increased when a weighted kappa statistic (range 0.55-0.78; median 0.68) was used. Kappa values were also calculated for specific categories and suggested an increasing concordance with increasing severity of the lesions, the categories of 'severe dysplasia' and 'invasive carcinoma' showing the highest agreement. The poor results for the 'moderate dysplasia' confirmed the need for combining this group with the 'severe dysplasia', as proposed in the Bethesda system. PMID- 8453015 TI - Comparison of planimetry and image analysis for the discrimination between normal and abnormal cells in cytological smears of suspicious lesions of the oral cavity. AB - Light microscope analysis of cytological smears of suspicious lesions of the oral cavity is used as a method for detecting early cancer in the oral cavity. The sensitivity of this approach can be improved by quantitative analysis of the cells in the cytological smears. We have compared the efficiency of planimetry and the Vids V system of image analysis, as quantitative methods for discriminating between normal and abnormal cells in cytological smears of suspicious lesions in the oral cavity. Both methods detected an increase in nuclear area and a decrease in cytoplasmic area in abnormal epithelial cells from dysplastic lesions of increasing severity. However, image analysis was better able to discriminate between benign and malignant cells on the basis of nuclear size. Thus the Vids V system of image analysis is more appropriate than planimetry for quantitative analysis of cytological smears from the oral cavity. PMID- 8453016 TI - Partial rescreening of all negative smears: an improved method of quality assurance in laboratories undertaking cervical screening. AB - Partial rescreening was carried out on 9633 cervical smears reported as negative by standard screening. Each slide was 'step-screened' at normal speed for 30 s. Thirteen false negative smears were detected by this method. No false negatives were revealed by conventionally rescreening 10% of the same study group. The sensitivity of the method was assessed by 'step-screening' 100 known positive smears. Of this group 92 were detected. The results indicate that partial rescreening is a sensitive method of quality assurance and should replace conventional 10% proportional rescreening, which is ineffective. PMID- 8453017 TI - Cytological criteria and diagnostic terminology in urinary cytology. PMID- 8453018 TI - Fine needle aspiration of pleomorphic lipoma: a potential pitfall of cytodiagnosis. PMID- 8453019 TI - Microfilaria in a fine needle aspirate from a breast lump: a case report. PMID- 8453020 TI - Cervical neoplasia and cytological manifestations of sexually transmitted diseases in HIV-seropositive prostitutes. PMID- 8453021 TI - Plasma concentrations and hemodynamic effects of intravenous, sublingual, and aerosolized nitroglycerin in patients undergoing cardiac catheterization. AB - Intravenous, sublingual, or aerosolized nitroglycerin was administered to 19 patients with coronary artery disease during clinically indicated cardiac catheterization. Eight blood samples were collected over 15 min from each patient, and analyzed for content of nitroglycerin, 1,2-glycerol dinitrate, and 1,3-glycerol dinitrate. Simultaneously, heart rate (HR), systolic blood pressure (SBP), and left ventricular end-diastolic pressure (LVEDP) were recorded. Plasma concentrations of nitroglycerin were highest after intravenous injection and lowest after sublingual tablets. Metabolite concentrations were highest after intravenous injection at early time-points; at later time-points, no between group differences could be detected. SBP was minimally affected by intravenous nitroglycerin but was significantly reduced by sublingual and aerosolized formulations. Minor fluctuations in HR were observed in association with all three formulations. LVEDP was reduced by all three formulations of nitroglycerin but most rapidly by the intravenous form. Overall, no differences were detected in hemodynamic responses caused by sublingual and aerosolized nitroglycerin. Efficacy of sublingual and aerosolized nitroglycerin in patients undergoing cardiac catheterization is equivalent. PMID- 8453022 TI - Inhibition of acetaminophen and lorazepam glucuronidation in vitro by probenecid. AB - The effect of probenecid on glucuronidation of acetaminophen and lorazepam in hepatic microsomes from various species was studied to see if in vitro results were consistent with previous in vivo observations. Mouse, rat, and human microsomes were incubated with acetaminophen and probenecid while monkey microsomes were incubated with lorazepam and probenecid. Glucuronidation rates in all species varied with substrate, protein, and detergent concentrations. Mice exhibited faster rates of glucuronidation than rats or humans. All species showed inhibition of glucuronidation of acetaminophen or lorazepam when probenecid was added. Analysis suggested competitive inhibition. Thus, in vitro studies support in vivo results and confirm that the inhibition takes place at the hepatic level. PMID- 8453023 TI - Human dolasetron pharmacokinetics: II. Absorption and disposition following single-dose oral administration to normal male subjects. AB - Dolasetron is a 5-hydroxytryptamine antagonist active at type III receptors; it is presently undergoing clinical evaluation for the reduction/prevention of cancer chemotherapy-induced nausea and vomiting. A previous study demonstrated that following intravenous administration to healthy male subjects, dolasetron disappeared extremely rapidly from plasma, and less than 1 per cent of the dose appeared in the urine. A major plasma metabolite, reduced dolasetron, peaked rapidly in the plasma. In this study, dolasetron was administered orally to healthy male subjects at doses ranging from 50 to 400 mg (mesylate monohydrate). Plasma concentrations of dolasetron were low and sporadic, and there was little excreted in urine; this prevented dolasetron pharmacokinetic analysis. Reduced metabolite concentrations peaked rapidly, with a median value of 1.00 h. The median terminal disposition half-life was 7.80 h. Median values for fraction of dose excreted in urine and renal clearance were 22.2 per cent and 2.56 ml min-1 kg-1. Whereas areas under the plasma concentration-time curves were proportional to dose, renal clearance increased with dose (p < 0.05). However, given dose proportionality to AUC, this is probably of little therapeutic consequence. Since reduced dolasetron has significant anti-emetic activity in the ferret model, it appears that this metabolite may play a significant role in pharmacodynamic activity. PMID- 8453024 TI - In vitro/in vivo correlation of prolonged release dosage forms containing diltiazem HCI. AB - Six preparations were considered: three multiple unit dosage forms (micropellets in capsules) (D, E and G) and one matrix tablet (B) were experimental prolonged release formulations, two non-disintegrating tablets (A and C) were commercial products. The in vitro dissolution behaviour of the differing formulations was investigated using the USP XXII paddle apparatus. The in vivo study was effected on a panel of 12 healthy volunteers. The two commercial tablets (A and C) showed mean dissolution time (MDT) of 1.34 and 1.44 h and td of 91 and 92 min, respectively; for prolonged release formulations (B, E, D, and G) MDT ranged between 2.28 and 4.23 h and td between 149 and 291 min. The mean residence time (MRT) was 8.68 and 6.47 h for tablets A and C, respectively; it ranged between 9.62 and 10.24 h for the multiple unit formulations E, D, and G and was 11.27 h for matrix B. Formulation B also showed the higher apparent elimination half-life t1/2 (7.12 h), while apparent t1/2 for all the other formulations were very similar, ranging between 5.04 and 5.28 h. High variability between the various formulations was found for Cmax and AUC values, and no relationships could be established with the type of formulation. An in vitro/in vivo correlation was found for all the formulations examined on the basis of analogous parameters (MDT and MRT); (r = 0.83, p < 0.05). In a few cases the Wagner-Nelson deconvolution method was applied to individual plasma level versus time curves and the corresponding absorption curves were obtained. In these cases the in vitro/in vivo correlation was tested on the basis of the comparison of the in vivo absorption curves with the in vitro dissolution profiles. This was accomplished using the 'Levy's plot' (per cent released versus per cent absorbed) approach and provided further support for the correlation found. PMID- 8453025 TI - Ceftriaxone pharmacokinetics in elderly subjects and penetration into epididymis. AB - In a prospective study, the epididymal penetration of ceftriaxone was evaluated in order to use it in the treatment of orchi-epididymitis in men. A bolus intravenous dose of 1 g of ceftriaxone was administered to 15 patients hospitalized for surgery as part of treatment for prostatic adenoma or prostatic cancer. Nine successive blood samples were collected in the interval from 0 to 24 h after administration, and epididymis samples were taken 0.75 h after administration. Concentrations of drug in all samples were assayed by a reverse phase-ion pairing high-performance liquid chromatography method with UV detection. The results showed that the pharmacokinetics of ceftriaxone in serum did not differ from those determined previously in healthy volunteers. The terminal half-life was 6.9 +/- 1.7 h, and the mean residence time 9.5 +/- 2.3 h. The volume of distribution was 0.144 +/- 0.018 1 kg-1 and the total body clearance 1.17 +/- 0.29 l h-1. The concentrations in tissue reached 27.2 +/- 6 micrograms g-1 in righ epididymis, and 25.4 +/- 6.2 micrograms g-1 in left epididymis. The tissue-versus-serum concentration ratios ranged from 0.175 to 0.545 (mean value, 0.295 +/- 0.099). The concentrations in serum and tissue observed in this study were in excess of the MICs for bacteria considered to be susceptible to ceftriaxone, particularly Neisseria gonorrhoeae and coliform bacteria. PMID- 8453026 TI - Metabolism of phenazopyridine by isolated rat hepatocytes. PMID- 8453027 TI - Biliary elimination of bromsulphthalein, phenolphthalein, and doxorubicin released from microspheres following intravenous administration. PMID- 8453028 TI - Bioavailability and disposition kinetics of HI-6 in Beagle dogs. AB - The absorption and disposition kinetics of HI-6 were determined in Beagle dogs given single doses (25 mg kg-1) of the drug by the intravenous, intramuscular, and oral routes. Concentrations of the oxime in plasma and urine were measured by HPLC. A two-compartment open model was used to describe the disposition curve following intravenous drug administration while a one-compartment open model with first-order absorption adequately described the data following intramuscular or oral administration of the dose. Extravascular distribution of HI-6 was limited (Vss 203 ml kg-1) and the drug was eliminated rapidly after intravenous administration (t1/2 46.5 min, MAT 55.4 min). Systemic clearance was 3.68 ml min 1 x kg. A major fraction of the dose (63.7 per cent) was excreted in urine over a 24-h collection period. Following intramuscular drug administration, the absorption half-life (t1/2(a), 5.3 min), MAT (17.1 min), Cmax (70.37 micrograms ml-1) and tmax (15.9 min) indicate that the drug was rapidly absorbed. Systemic availability was 83.43 per cent after oral drug administration, absorption was preceded by a lag time (23.2 min). The t1/2(a) (41.5 min), MAT (81.6 min), Cmax (4.30 micrograms ml-1) and Tmax (90.6 min) indicate somewhat delayed absorption. Systemic availability (11.38 per cent) and the fraction of dose excreted unchanged in the urine (9.3 per cent) show that the drug was poorly absorbed. The apparent half-life (58.0 min) and MRT (137.6 min) following oral administration were significantly longer (p < 0.05) than following intravenous or intramuscular administration suggesting that the rate of absorption from the gastrointestinal tract decreases the elimination rate of the drug. In conclusion, HI-6 has limited distribution within the body, is rapidly eliminated mainly by renal excretion unchanged in the urine, and the bioavailability (i.e. rate and extent of absorption) of the drug varies with the route of administration. PMID- 8453029 TI - Characterization of brain angiotensin II AT2 receptor subtype using [125I] CGP 42112A. AB - Recently two subtypes of angiotensin receptors have been described, AT1 and AT2. Currently used radiolabeled agonists and antagonists are not able to discriminate between these receptors subtypes. Here we characterize the use of [125I] CGP 42112A, a novel, specific ligand for AT2 receptors, in a membrane binding assay and in autoradiography of brain sections of 2 week old rats. [125I] CGP 42112A bound with high affinity and autoradiography revealed binding selectively localized to areas known to express the AT2 receptor subtype only. CGP 42112A, angiotensin II, angiotensin III and PD 123177 competed for [125I] CGP 42112A binding, with potencies consistent with high affinity and specific binding to AT2 receptors. Thus [125I] CGP 42112A will be a useful new tool to study AT2 receptors. PMID- 8453030 TI - Cocaine alters body temperature and behavioral thermoregulatory responses. AB - This study examined the effects of cocaine HCl and ambient temperature on the core body temperature of the rat. To further examine the mechanisms of cocaine induced changes in temperature regulation, the effects of cocaine on behavioral thermoregulatory responses were also observed. At normal room temperature (20 degrees C) cocaine produced a reduction in core body temperature. At a higher ambient temperature (27 degrees C), however, cocaine produced hyperthermia. When given a choice between normal and warm environments, cocaine-injected animals spent significantly less time in the warm environment than did control animals, but had significantly lower core body temperature. These results suggest that cocaine treatment may lower the thermoregulatory set point. PMID- 8453031 TI - Descending influence on dorsal horn neuronal hyperactivity in a rat model of neuropathic pain. AB - The effect of nucleus raphe magnum (NRM) stimulation on the abnormal activity of lumbar dorsal horn neurones in rats with a chronic nerve constriction injury was studied. Neurones on the two sides of the spinal cord were extracellularly recorded in anaesthetized and curarized preparations. The neurones on the side ipsilateral to the injury showed a spontaneous firing frequency higher than that of the opposite intact side (25.8 +/- 1.9 spikes s-1 vs 4.5 +/- 1.3 spikes s-1). The hyperactivity was reduced to a mean value of 9.3 +/- 1.3 spikes s-1 by NRM stimulation using parameters able to selectively inhibit the noxiously evoked neuronal responses on the intact side. The results indicate that the hyperactivity is a phenomenon related to chronic pain that may be modulated by the endogenous pain control system. PMID- 8453032 TI - Effects of codeine, naproxen and dexamethasone on formalin-induced pain in the naked mole-rat. AB - A dilute solution of formalin (20 microliters of 10% formalin) was injected subcutaneously in the dorsal right hind paw of the naked mole-rat. The injection of the dilute formalin produced two periods of pain behaviour, the early (0-5 minutes) and the late phase (25-60 minutes). These were quantified as the total time spent licking the injected paw. Codeine phosphate (10, 25 or 50 mg kg-1) significantly reduced pain behaviour in both the early and late phase. Codeine administration also induced aggressive, hyperactive behaviour and motor impairment that was naloxone (2 mg kg-1) reversible. Naproxen (200 mg kg-1) and dexamethasone phosphate (30 mg kg-1) significantly reduced licking activity in the late phase only. PMID- 8453033 TI - Changes in large dense-core vesicles during maturation of the rat neuromuscular junction. AB - The proportion of large dense-core vesicles (LDCVs) in motor nerve terminals of the rat biceps brachialis muscle was evaluated from embryonic day 20 to 4 weeks postpartum as well as in the adult. A progressive decrease was observed up to 3 weeks postpartum when maturation of the endplates is achieved. Differences compared with the adult were no longer significant at 4 weeks postpartum. Three types of LDVCs, classified according to their size and the core density, were detected. Their relative proportion did not vary significantly during the period of life examined. The high proportion of LDCVs during early development and their persistence at a low level in the adult suggest that they might play a role in the maturation and maintenance of the endplates. PMID- 8453034 TI - Neurotrophin-3 upregulates NGF receptors in a central nervous system glial cell line. AB - The low-affinity nerve growth factor (NGF) receptor (LNGFR) binds the neurotrophins NGF, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) with similar affinities. Here we report on the ability of NT-3 to regulate the expression of the LNGFR in C6 glioma cells. LNGFR-like immunoreactivity (LNGFR-IR) was examined in C6 cells treated for 16 h with NT-3 and exposed to the antibody 192-IgG followed by immunoglobulins conjugated with colloidal gold by means of ultrastructural morphometric analysis. Untreated C6 cells exhibited some positive LNGFR-IR, while C6 cells treated with NT-3 displayed significantly increased (2.3 fold) LNGFR-IR. The increase in LNGFR protein was accompanied by a greater quantity of LNGFR mRNA in NT-3-treated cells. Thus, LNGFR can be upregulated by the structurally related neurotrophin NT-3. PMID- 8453035 TI - Expression of NADPH-diaphorase activity by guinea-pig paratracheal neurones. AB - Pharmacological evidence suggests that nitric oxide (NO) is involved in non adrenergic, non-cholinergic, nerve mediated responses seen in guinea-pig trachealis muscle. The synthetic enzyme for NO (NO synthase) has recently been shown to be responsible for neuronal NADPH-diaphorase activity. Therefore, to determine whether intrinsic paratracheal neurones could be a source of NO in the trachea, expression of NADPH-diaphorase activity was examined histochemically using whole mount preparations of the tracheal plexus. Many paratracheal neurones were found to express moderate to high levels of NADPH-diaphorase activity and are thus likely to be a source of NO in this tissue. This observation provides further evidence that NO is involved in the regulation of relaxation in airway smooth muscle. PMID- 8453036 TI - C-fos expression and 2-deoxyglucose uptake in the olfactory bulb of odour stimulated awake rats. AB - Using a selective monoclonal Fos antibody, we have studied the expression of the c-fos proto-oncogene in the olfactory bulb of awake rats stimulated with propionic acid vapours. We have perfected a method which allows the comparison of patterns of either cellular c-fos immunoreactivity or glomerular 2-deoxyglucose uptake in the same olfactory bulb. C-fos was expressed in local bulbar interneurones, principally granule cells. We observed that the low level of basal c-fos expression raised significantly under olfactory stimulation in the bulbar column defined by the foci of high 2-deoxyglucose glomerular uptake. This is the first demonstration that c-fos expression can be triggered by afferent olfactory input in the olfactory bulb in normally breathing awake rats. These data support the assumption that the olfactory bulb is a suitable model to elucidate the priming conditions and functional involvement of Fos protein synthesis triggered by physiological sensory stimulation. PMID- 8453037 TI - NADPH-diaphorase staining in autonomic and somatic cranial ganglia of the rat. AB - Using NADPH-diaphorase staining as a marker for the enzyme nitric oxide synthase (NOS) we have investigated the possible sites of nitric oxide (NO) synthesis in a number of cranial ganglia in the rat. Intense staining was found in the majority of neurones in the sphenopalatine ganglion, suggesting a major role for NO in postganglionic parasympathetic systems in the head. In contrast the neurones of the superior cervical ganglion were not stained by this histochemical procedure but were enveloped by a mesh of intensely staining fibres. As preganglionic sympathetic neurones in the intermediolateral horn of the spinal cord stain for NADPH-diaphorase, our results would suggest that NO acts as a neurotransmitter between pre- and post-ganglionic sympathetic neurones. PMID- 8453038 TI - Synaptic degeneration is the primary neuropathological feature in prion disease: a preliminary study. AB - The range of neuropathology found in cases of prion disease is considerable. The pathology present in dendrites and axons is associated with a marked loss of spines and synaptic contacts. It is probable that this loss underlies the functional and neurological deficits in the disease. Immunocytochemical re examination of 2 cases of inherited disease with a 144 bp prion gene insertion with no characteristic pathology (i.e. spongiform change, astrocytosis and gliosis), together with 3 typical cases of prion disease (CJD), with antibodies to synaptophysin and synaptic protein demonstrated the presence of synaptic "plaque-like" lesions throughout the temporal cortex and cerebellum. In addition, examining the tissue by image analysis demonstrated a greater than 30% reduction in the relative synaptic index in all the prior disease cases when compared with controls. Synaptic disorganization and/or loss is a fundamental and constant feature of prion disease, irrespective of the presence or absence of spongiform change, neuronal loss and severe gliosis. Assessment of the extent and location of synaptic deficits might produce a more accurate documentation of the degree of neuronal disorganisation occurring during the course of prion disease. PMID- 8453039 TI - Transforming growth factor-beta 1 is in plaques in Alzheimer and Down pathologies. AB - Transforming growth factor-beta (TGF-beta) is a major modulator of the extracellular matrix and cell growth, and shows affinity for and interaction with several substances present in plaques in Alzheimer's disease (AD). In order to examine a possible role of TGF-beta in plaque biogenesis, we studied its distribution in the limbic system of AD and Down's syndrome (DS) brains. Select plaques displayed TGF-beta 1 immunoreactivity in AD and DS. TGF-beta 1 plaques were mainly located in the molecular layer of the dentate gyrus in AD, while in DS TGF-beta 1 plaques were preferentially located in the entorhinal cortex. In AD, TGF-beta 1 immunoreactivity was also shown in neurofibrillary tangles. The presence of TGF-beta 1 in plaques suggests that TGF-beta 1 may play a role in the cascade of events leading to plaque formation. PMID- 8453040 TI - On the origin of Alzheimer's disease: a hypothesis. AB - There is no unifying hypothesis to account for the anatomical distribution of neuropathology, the involvement of beta-amyloid precursor protein (beta APP) and the role of increasing age in triggering the Alzheimer disease process. We report here that layer II pre-alpha neurones in transentorhinal and entorhinal cortex contain more beta APP immunoreactivity than other cortical neurones in normal individuals. This immunoreactivity increased in the early stages of Alzheimer's disease and was lost as the disease progressed. These neurones are known to undergo genetically programmed re-sprouting and synaptogenesis during the fifth and sixth decades of life. We hypothesize that these phenomena are related and that the Alzheimer's disease process originates in entorhinal cortex neurones due to the enhancement of their normally high content of beta APP during age-related resprouting. PMID- 8453041 TI - Age dependence of striatal neuronal death caused by mitochondrial dysfunction. AB - Several lines of evidence point to a decline in mitochondrial efficiency with age. The relationship between age and sensitivity to Huntington disease-like neuronal death in the striatum induced by the mitochondrial inhibitor 3 nitropropionic acid (3-NP) was examined. 3-NP has been shown to cause degeneration of striatum, hippocampus, and thalamus in rat and of caudate-putamen in humans. We administered single doses of 3-NP intraperitoneally to rats of various ages. Animals older than 4 months exhibited a far greater susceptibility to striatal neurotoxicity and mortality compared with younger animals. These results are discussed in the context of age-dependent metabolic impairment, which may be a key factor in the etiology of neurodegenerative disorders such as Huntington's disease and Alzheimer's disease. PMID- 8453042 TI - Limbic-dependent recognition memory in monkeys develops early in infancy. AB - Infantile amnesia, the absence of memories from infancy and early childhood, has been attributed to an immaturity of the limbic system in infancy. Contrary to this view, we now report that limbic-dependent recognition memory is present as early as one month of age in monkeys. Memory measured by the paired-comparison preferential looking task, normally present in infant monkeys within the first month of life, is absent after damage to the amygdaloid complex and hippocampal formation, suggesting that limbic structures make a critical contribution to visual recognition memory even at this early age. The findings reopen the question of the locus of the neural immaturity that underlies infantile amnesia. PMID- 8453043 TI - Scopolamine affects short-term memory but not inferior temporal neurons. AB - Effects of scopolamine on performance of a delayed matching-to-sample task and on the properties of neurons in anterior-ventral inferior temporal (IT) cortex were examined in two monkeys. Both monkeys were impaired on the task after systemic administration of scopolamine, suggesting that scopolamine disrupts recency memory. Despite the behavioral deficit, neurons in IT cortex, a region having an important role in visual memory and neuronal properties consistent with that role, were largely unaffected by scopolamine. This dissociation between the behavioral and neuronal effects of scopolamine indicates that the drug either acts at a different site or disrupts unobserved mechanisms at the IT site. PMID- 8453044 TI - Recordings of the evoked auditory wave P1 from the pons during natural and drug induced REM. AB - A positive component of the middle latency auditory evoked response recorded from the vertex, the P1 wave, was found to be sensitive to changes in the wakefulness sleep states. We report here that this wave can be recorded from the pons of chronically prepared cats. During natural REM sleep and REM induced by micro injections of carbachol and neostigmine into the pons the pontine P1 had amplitudes much higher than during slow wave sleep (SWS). The increase in amplitude was dose dependent. Scopolamine had a profound and long-lasting weakening effect on the wave. These results indicate a relation between the P1 wave and the cholinergic generator mechanism for REM sleep. Also, our results support the role of an increased recruitment of the pontine neurones in the generation of REM sleep. PMID- 8453045 TI - Long-term potentiation and depression in the ventral horn of rat spinal cord in vitro. AB - The aim of this study was to see whether long-term potentiation (LTP) and/or long term depression (LTD) of synaptic efficacy could be induced in the ventral horn of the rat spinal cord. Transverse slices were cut from neonatal rat spinal cords and maintained in vitro. Field potentials were recorded in the ventral horn in response to stimulation of the dorsal horn-intermediate nucleus region of the slice. Tetanic stimulation at 100 Hz (6 bursts of 50 pulses with 10 s between bursts) resulted in long-term potentiation in 25% of slices, long-term depression in 33% of slices and no long-lasting change of field potential amplitude in the rest. The long-term changes lasted at least 2.5 hours. The principal conclusion of the work is that LTP and LTD can be elicited in the ventral horn. PMID- 8453046 TI - Habenula lesions attenuate lateral hypothalamic analgesia in the formalin test. AB - The purpose of the experiment was to determine the role of the habenula complex (Hb) in lateral hypothalamic (LH) analgesia for tonic pain. The results demonstrate that lesions of the Hb attenuated LH analgesia in the formalin test. The result of Hb lesions cannot be attributed to non-specific brain damage since bilateral caudate nucleus lesions of similar extent to the Hb complex damage failed to modify the analgesic effect of LH stimulation. The critical damage was probably to the lateral habenula nucleus since it receives a major input from the LH. In addition to the primary finding, we observed that lesions of the Hb had no effect on the baseline response to formalin. PMID- 8453047 TI - Is the trunk a reference frame for calculating leg position? AB - Naive subjects and dancers were instructed to raise a leg laterally toward 45 degrees. The final position reached by the leg by each group of subjects was quite different: 48 degrees in dancers, i.e. close to the required value, and 56 degrees in the naive subjects. The reason for this difference was investigated. During the body weight transfer toward the supporting side prior to the leg movement, naive subjects inclined both leg and trunk laterally, whereas the dancers' trunk remained vertical. It was observed that in naive subjects the trunk inclination and the overestimation of the final leg position were closely correlated. The results suggest that in both naive subjects and dancers, the trunk axis serves as a reference value for calculating the leg position. PMID- 8453048 TI - Neuronal interaction between VIP and vasopressin neurones in the rat suprachiasmatic nucleus. AB - Synaptic interaction between VIP-like immunoreactive (VIP-LI) and vasopressin like immunoreactive (VASO-LI) neurones both of which are main neuronal components in the SCN was investigated using double labelling immunoelectron microscopy. VIP LI axons were identified as having synaptic contacts with VASO-LI neuronal perikarya and dendrites. VIP-LI axons also formed synapses on non-immunoreactive dendrites or dendritic spines. In addition to the above findings, VIP-LI neuronal elements also formed synaptic contacts with other VIP immunoreactive structures. PMID- 8453049 TI - Presence of cannabinoid binding sites in the brain from early postnatal ages. AB - The present study demonstrates the presence of cannabinoid receptors in the brain from early postnatal ages. Specific and saturable binding was observed in the forebrain and remaining brain from early postnatal ages (2 and 5 days after birth). Female neonate forebrain exhibited a higher receptor density at 2 days after birth than males, but this trend was inverted at 5 days. From postnatal day 10, the receptors could be measured in more defined brain areas, i.e. the striatum, limbic forebrain and ventral mesencephalon. The ontogeny of the receptors in these three areas was relatively similar, exhibiting a progressive increase which maximised on days 30 or 40 and then subsequently decreased to adult values. Subtle sexual dimorphism was found in the striatum and ventral mesencephalon but not the limbic forebrain. PMID- 8453050 TI - Delayed increase in intracellular Na+ in cerebral cortical slices during severe hypoxia as measured by double quantum filtered 23Na+ NMR. AB - We have used double quantum filtered (DQF) 23Na+ nuclear magnetic resonance (NMR) spectroscopy without shift reagents in order to monitor intracellular Na+ (Na+i) in a cortical brain slice preparation. The external Na+ (Na+o) signal was reduced by 95% by the DQF sequence compared with the directly observed 23Na+. The DQF 23Na+ signal is not exclusively due to Na+i, however, as 40% of this signal appears to arise from Na(+)-ions interacting with extracellular membrane proteins or proteins exposed at the cut surfaces of the slices. Veratridine increased instantly the DQF 23Na+ signal so that it reached 130.4 +/- 5.0% by 12 min. This shows that there was a significant contribution from Na+i in the DQF 23Na+ NMR spectra. Hypoxia of 30 min duration in the presence of 10 nM glucose did not influence intensity of the DQF 23Na+ signal. Aglycaemic hypoxia caused complete collapse of phosphocreatine (PCr) within 7 min whereas DQF 23Na+ first increased 15 min after the insult. This increase reached its maximal value of 125% after 25 min. There was an incomplete recovery of the DQF 23Na+ after aglycaemic hypoxia to 110% of the control value parallel to poor metabolic recovery. The presence of 10 mM extracellular Mg2+ had no apparent effect on the aglycaemic hypoxia-induced rise in Na+i indicating that it was linked to Ca2+ influx. Tetrodotoxin (TTx, 4.7 microM) did not influence the rise of Na+i caused by aglycaemic hypoxia. These results indicate that elevation of Na+i is a late consequence of energy failure in the cerebral cortex. PMID- 8453051 TI - Hydrocortisone and 11-desoxycortisone modify acetylcholine receptor channel gating. AB - Acute exposure of the nicotinic acetylcholine receptor (AchR) to hydrocortisone (HC) induced a dose-dependent reduction in the channel open time and burst duration and an increase in the closed time, with no changes in channel amplitude. Similar effects were observed with 11-desoxycortisone, thus suggesting that the oxygen atom at position 11 is not required for channel modification. The changes were observed when HC was added to either face of the membrane, but the concentration dependence of the effect differed, indicating a certain sidedness of the corticoid action. The results are consistent with the corticoids acting either at a site on the AChR which can be reached via a membrane pathway or at the lipid annulus immediately surrounding the AChR, i.e. at the lipid-protein interface. PMID- 8453052 TI - A glycine antagonist 7-chlorokynurenic acid attenuates ischemia-induced learning deficits. AB - Transient global ischemia can result in permanent neuronal damage and impairments in learning and memory. We investigated the therapeutic potential of 7 Chlorokynurenic acid, a potent antagonist at the glycine-modulatory site on the NMDA receptor, in terms of both neuroprotection and behavioral outcome in rats following transient forebrain ischemia. Intraventricular administration of the drug immediately before ischemia significantly attenuated ischemia-induced CA1 pyramidal cell loss. Moreover, ischemic rats treated with 7-Chlorokynurenic acid showed unimpaired acquisition of a delayed nonmatching to sample task 8 weeks following surgery, whereas saline-treated ischemic rats were significantly impaired. These data provide preliminary evidence that the glycine site may be an appropriate target for therapeutic agents in ischemia. PMID- 8453053 TI - Effect of alcohol on elevated aggressive behavior in male transgenic TGF alpha mice. AB - The effect of alcohol on aggressive behavior was studied in the highly aggressive transgenic TGF alpha male mouse. In contrast to findings obtained in other aggressive animals, low and moderate doses of alcohol failed to reduce this behavior in the TGF alpha mice; only a high dose reduced aggression. The plasma levels of alcohol were similar in the TGF alpha mice and non-transgenic control mice. However, the loss of righting reflex following an alcohol administration was significantly lengthened in the TGF alpha mice. These results suggest that the male TGF alpha mice can be used to investigate the mechanisms determining the physiological sensitivity to alcohol. Furthermore, these mice represent the first animal model supporting the findings obtained in humans that alcohol maintains pathological aggression. PMID- 8453054 TI - Autoradiographic localization of binding sites for neuropeptide Y and bradykinin on astrocytes. AB - The cellular localization of binding sites for the vasoactive peptides 125I neuropeptide Y (NPY) and 3H-bradykinin (BK) was studied in explant cultures of rat cerebellum, brain stem and spinal cord by means of autoradiography. The majority of astrocytes in these cultures expressed binding of 125I-NPY and 3H-BK over their cell bodies and processes. Simultaneous staining of the cultures with anti-glial fibrillary acidic protein (GFAP) has shown that the labelled cells were GFAP-positive and could therefore be identified as astrocytes. In addition to glial cells, a great number of neurones also revealed binding sites for the neuropeptides. Our autoradiographic findings together with recent electrophysiological studies provide good evidence for the existence of NPY- and BK-receptors on astrocytes. PMID- 8453055 TI - How does environmental enrichment aid performance following cortical injury in the rat? AB - Understanding how postoperative environmental brain damage in animals may help in devising treatment regimes for brain injured humans. This study tests Finger's hypothesis that EC increases the animal's ability to switch to alternative cues when brain damage renders the cues normally used in performing the task less salient or unavailable. Following preoperative water maze training to visual cues, rats were given either bilateral occipital lesions or sham operations, housed in either EC or standard conditions and then tested in the water maze in alternating visual and non-visual cue conditions. We found no evidence that postoperative EC helped lesioned rats to switch to non-visual cues when visual cues were unavailable. PMID- 8453056 TI - Single-fibre EPSPs in layer 5 of rat visual cortex in vitro. AB - Simultaneous intracellular recordings were made from pairs of synaptically connected layer 5 pyramidal neurones less than 150 microns apart, in slices of rat visual cortex. Action potentials were evoked in one cell of a pair by depolarizing current pulses, while spike-triggered averaging was employed to reveal connections in the other cell and vice versa. Only 4 excitatory postsynaptic potentials (EPSPs) (0.7-1.2 mV) were recorded out of 270 cell pairs tested, equivalent to a connection probability of less than 0.02. Therefore, single-fibre EPSPs between pyramidal cells in layer 5 are less frequent, but individually larger in amplitude, than those found previously between pyramidal cells in layer 2/3 of rat visual cortex. PMID- 8453057 TI - MK801 induces immediate-early gene proteins and BDNF mRNA in rat cerebrocortical neurones. AB - Recent studies have shown that MK801, a potent phencyclidine receptor ligand, causes pathomorphological changes in rat cerebrocortical neurones. Here we report that doses of MK801 (1 and 5 mg kg-1) which have been shown to produce pathomorphological changes, induce the expression of immediate-early gene proteins (IEGPs) and brain-derived neurotrophic factor (BDNF) mRNA in rat cerebrocortical neurones. Blockade of central muscarinic receptors which has been shown to prevent MK801-induced pathomorphological changes in cerebrocortical neurones, also prevented MK801-induced expression of IEGPs and BDNF mRNA. The transiently increased expression of BDNF mRNA may be an acute compensatory response of these neurones to MK801-induced injury. PMID- 8453058 TI - BDNF and trkB mRNA expression in the rat hippocampus following entorhinal cortex lesions. AB - Quantitative in situ hybridization was used to determine whether the prevalence or topographical distribution of brain-derived neurotrophic factor (BDNF) or tyrosine receptor kinase (trk) B mRNA is altered in the hippocampal formation following lesions of excitatory afferents from the entorhinal cortex which provides an external source of innervation for the hippocampal formation. BDNF mRNA levels were not altered in the hippocampal formation up to 10 days following entorhinal cortex lesions (ECLs). The levels of mRNA coding for all known forms of trkB receptors also remained unchanged. The prevalence of the synaptic plasticity marker SNAP-25 mRNA was increased in the CA2 and CA3 pyramidal cell layers and the dentate gyrus by 6 days following ECLs and remained elevated at 10 days following ECLs. Our findings indicate that hippocampal neuron sprouting which occurs in response to ECLs is not the result of changes in the expression of the BDNF or trkB mRNA. PMID- 8453059 TI - Identification of an AP-1 transcription factor binding site within the human cholecystokinin (CCK) promoter. AB - Neuropeptide gene expression, i.e. proenkephalin A, may be modulated by activating protein (AP-1) transcription factor complexes which associate with specific DNA sequence motifs, known as the AP-1 binding sites. Gel mobility shift assays revealed that nuclear extracts prepared from a human neuroblastoma cell line, SK-N-MC, bind to the 5'-CTGCGTCAGCG-3' motif, present within the human cholecystokinin (CCK) promoter. In contrast, the mutated 5'-CTGCAACAGCG-3' motif did not bind any specific protein complex. In vitro run-off transcription and Western blot analysis revealed the expression of the protooncogenes Fos and Jun. This suggests that Fos/Jun homo- or heterodimeric complexes may interact with the 5'-CTGCGTCAGCG-3' motif, present within the human CCK promoter. PMID- 8453060 TI - Quinolinate and kainate facilitate magnesium penetration into brain tissue. AB - To study the penetration of magnesium ions from blood into brain tissue, magnesium content in serum and hippocampus of normal and of excitotoxically affected rats was estimated after a single subcutaneous injection of magnesium sulphate (600 mg kg-1). In normal rats Mg2+ levels in serum rose from 1 to 6 mM, while that of the hippocampus remained constant, provided the brains were perfused before magnesium measurement. Following unilateral intracerebroventricular injection of the excitotoxic glutamate analogues, quinolinate or kainate acid, Mg2+ levels increased up to 38% on the (unaffected) contralateral side. Since magnesium is known to prevent glutamate-mediated neurodegeneration, our findings on the accessibility of exogenously applied magnesium may justify further investigations on the utility of magnesium for a therapeutic approach to limiting excitotoxic brain injury in human patients. PMID- 8453061 TI - Ultrastructural neuropathology in murine trisomy 16 hippocampal grafts. AB - Trisomy 21, Down syndrome individuals demonstrate Alzheimer's disease-associated neuropathology at post mortem. The amyloid precursor protein, one of the pathological proteins is encoded for on chromosome 21. Mouse chromosome 16 is syntenic to human chromosome 21 for the region spanning the amyloid gene. We have previously reported the appearance of Alzheimer's disease-associated neuropathological proteins in cortical grafts derived from Trisomy 16 mice at 4-6 months survival. This paper reports the ultrastructural observations of large and multiple deposits of intracellular lipofuscin within these trisomic grafts at 12 months survival along with increased numbers of free ribosomes, extended Golgi apparatus and endoplasmic reticulum, membrane degeneration and abnormal axonal profiles. Similar but less severe neuro-degeneration is occasionally observed within 18-month-old normal, mouse hippocampal tissue and rarely observed in age matched control grafts. PMID- 8453062 TI - Accumulation of the beta amyloid precursor protein at sites of ischemic injury in rat brain. AB - We used various antibodies to the beta amyloid precursor protein (APP) of Alzheimer's disease to study changes in the cellular distribution of APP in experimental ischemic brain injury. In contrast to sham operated controls, rats with repeated reversible occlusions of one middle cerebral artery showed striking APP reactivity in astrocytic processes in perifocal regions and white matter tracts. Dystrophic axons and neurons with accumulated APP were also evident in the ipsilateral neocortex and hippocampus. Such changes were also apparent in rats subjected to partial forebrain ischemia by bilateral occlusion of the carotid arteries. Our studies suggest that focal ischemic insults or chronic hypoperfusion leads to increased accumulation of APP in surviving brain cells that may pertain to enhanced beta amyloid deposition in Alzheimer's disease. PMID- 8453063 TI - A model of the inward current Ih and its possible role in thalamocortical oscillations. AB - We investigated the kinetic properties of the hyperpolarization-activated inward current (Ih) of thalamocortical (TC) neurons. Recently, it was shown that this current is characterized by different time constants of activation and inactivation, which was in apparent conflict with the single-exponential time course of the current. We introduce here a model of Ih based on the cooperation of a slow and a fast activation variable and show that this kinetic scheme accounts for these apparently conflicting experimental data. We also report that following the combination of such a current with other currents seen in TC cells, one observes several types of oscillating behavior, similar to the slow oscillations and the spindle-like oscillations seen in vitro. PMID- 8453064 TI - The 70 kDa peroxisomal membrane protein: an ATP-binding cassette transporter protein involved in peroxisome biogenesis. AB - The 70 kDa peroxisomal membrane protein (PMP70) is a major component of peroxisomal membranes. cDNAs for human and rat PMP70 have been cloned and sequenced and the gene mapped to human chromosome 1p21-22. The predicted amino acid sequence showed homology to members of the ATP-binding cassette transporter family. In humans, mutations in the PMP70 gene have been found in a subset of patients with Zellweger syndrome, a lethal inborn error of peroxisome biogenesis. These results suggest that PMP70 functions in transporting molecules or possibly peptides across the peroxisomal membrane and has an important role in peroxisome assembly. PMID- 8453065 TI - The transporters associated with antigen presentation. AB - Two new members of the ABC superfamily of transporter genes have recently been identified within the Major Histocompatibility Complex in man, rat and mouse. Although the exact function of these genes is not known, they have been shown to be necessary for the presentation of peptides derived from the degradation of cytoplasmic protein antigens to the cellular immune system. For this reason they have been named TAP1 and TAP2 (for Transporter associated with Antigen Presentation). Each gene encodes one membrane spanning domain and one region homologous to the ATP binding domains that characterise the superfamily. The two proteins encoded by the TAP genes form a complex that is localised to the membranes of the endoplasmic reticulum and cis-golgi. Their most likely function is to transport short peptides, that lack signal sequences, from the cytoplasm to the endoplasmic reticulum, although the evidence for this is still indirect. PMID- 8453066 TI - Bacterial signal peptide-independent protein export: HlyB-directed secretion of hemolysin. AB - Bacterial ABC transporter proteins are associated with a great number of cellular processes. While many of the best characterised examples are involved in the import of small molecules into the cell, others mediate export of substrates, especially hydrophilic proteins. This article focuses on these bacterial ABC exporters, in particular the HlyB protein which is central to secretion of the 110 kDa hemolysin across both the cytoplasmic and outer membranes. This is an example of non-conventional protein export which does not require an N-terminal signal sequence or the cellular SecA-dependent machinery. PMID- 8453067 TI - [CT and MRI of the retroperitoneum and pelvis]. PMID- 8453068 TI - [High-resolution CT of the dentate alveolar ridge in comparison with histological thin section preparations]. AB - Human bone segments of the toothed jaw were scanned using high-resolution CT with axial and coronal contiguous 1 and 2 mm slices. The bone segments were sliced analogous to the performed CT image positions. Contact films and micro-sections were made from the cuttings. Length and width of the teeth, the thickness of the alveolar bone and the distance between bone and dental surface were measured. Comparison of the CT measurements with contact films and histological specimen yielded best results for axial slices with 1 mm slice thickness (mean error 0.3 0.5 mm). Coronary oriented slices showed an error of 0.3-1.6 mm. 3D-reformatting can improve spatial orientation for axially produced image series. For CT imaging of the toothed jaw concerning the dento-alveolar structures, contiguous axial scanning with 1 mm slice thickness appears to be the concept of choice. PMID- 8453069 TI - [MRI of the temporomandibular joint. Demonstrability and significance of the retro-articular vascular plexus]. AB - The retro-articular vascular plexus of the temporomandibular joint (TMJ) is of great importance for the function of this joint. Aim of this study was to determine the amount of increase of signal intensity in the retro-articular vascular plexus after intravenous injection of contrast medium and to figure out potential advantages of this procedure. The posterior band of the articular disc- a landmark in the diagnosis of disc dislocations--becomes prominent after injection of contrast medium. Forty-five temporomandibular joints were studied before, and after intravenous injection of contrast medium with magnetic resonance imaging (MRI) using T1-weighted images in parasagittal plane. In all cases a measurable increase of signal intensity was demonstrable in healthy volunteers as well as in patients with normal or pathological TMJ findings. In 53.3% of cases the posterior band was better differentiable after administration of contrast medium. In patients with suspicion of pathological features in series without contrast medium, in 27.3% of those cases administration of contrast medium led to a more precise--"diagnostic"--evaluation of disc location. The study emphasizes the use of contrasts medium for evaluations of disc dislocation with MRI in cases of pathological or unclear findings in precontrast MRI series. PMID- 8453070 TI - [Radio-opaque structures in the lumen of the maxillary sinus--value of computerized tomography in the diagnosis of maxillary aspergillosis]. AB - 11 patients with radio-opaque concrements in the sinus maxillaris underwent a preoperative computerized tomographic examination of the sinus maxillaris and the sinus concrements. 8 patients (72.7%) with the occurrence of radio-opaque concrements presented postoperative a histological and microbiological infection with aspergillus fumigatus. The CT-numbers of radio-opaque concrements in patients with aspergillus were 2802 +/- 302.4 HU (Hounsfield Unit). Concrements of patients without aspergillus infection (n = 3) had lower density (368.6 +/- 149.1 HU; p < 0.001). The root filling materials showed nearly the same CT numbers in patients with aspergillus infection (2537 +/- 398.5 HU) and in patients without aspergillus infections (2544.3 +/- 460.6 HU). Density of root filling material was at the same level as density of radiopaque concrements in patients with aspergillus infections. According to CT-examinations a direct connection between root filling materials and aspergillus infection was noted. Therefore in patients with radio-opaque concrements computerized tomographic examination helps to determine the kind of sinus infection. PMID- 8453071 TI - [Magnetic resonance tomography of so-called transient osteoporosis. Primary diagnosis and follow-up after treatment]. AB - Transient osteoporosis or transient bone marrow oedema is a rare cause of acute hip pain that predominantly affects adults of middle and younger age. We report on the MR image in 8 patients with transient bone marrow oedema of the hip and in one patient with affection of the knee joint. In three of these, sympathetic nerve blockade has been performed. The MR image after sympathicolysis is discussed. PMID- 8453072 TI - [Ultrasound velocity measurement in the diagnosis of postmenopausal osteoporosis]. AB - We evaluated ultrasound transmission velocity as an indicator for osteoporosis at the os calcis of both feet and at the proximal phalanges of DII and DIII of both hands in 74 female subjects (22 premenopausal, 29 postmenopausal non-osteoporotic and 23 postmenopausal osteoporotic). In addition dual x-ray absorptiometry (DXA) of the lumbar spine was performed in 30 women and a combined cortical thickness index (CCT-index) of os metacarpale II was calculated from hand radiographs in 29 women. Ultrasound velocity at all sites slightly decreased in premenopausal women with age and declined significantly after menopause. At the hand postmenopausal osteoporotic women had significantly lower velocities than normal postmenopausal or premenopausal women while no difference could be seen at os calcis. An only poor or moderate correlation between ultrasound velocity at all sites and DXA of the lumbar spine and a good correlation between the CCT-index and velocity at the fingers indicate that ultrasound velocity is not only affected by bone density but even more by structural properties. PMID- 8453074 TI - [Color-coded three-dimensional reconstruction from spiral CT data sets: physical viewpoint for improvement of the method]. AB - This paper demonstrates the possibility of improving the spatial depth impression of colour-coded three-dimensional reconstructions by modulation of colour saturation. Patients were observed with spiral computed tomography (slice thickness 10 mm, table feed 10 mm/s, reconstruction of overlapping axial images at 2 mm increment). Interesting anatomical and pathological objects (vessels, organs, tumours, metastases) were segmented, colour-coded, and reconstructed three-dimensionally. Spatial depth impression of the coloured objects could be improved by modulating not only the brightness, but also the colour saturation. PMID- 8453073 TI - [3D-CT and angiography of cast preparations of pelvic vessels: demonstration of arterial blood supply of the acetabulum]. AB - Anatomical studies of the arterial blood supply of the acetabulum were performed utilizing conventional angiography and 3D-CT on 27 hip specimens. In 16 cases the arterial arborization was filled with undiluted barium-sulfate via the internal artery and in 11 cases with a solution of resin and lead power. 3 specimens out of 30 were excluded because of extravasation using barium-sulfate in one case and incomplete filling with resin in 3 cases. Conventional angiograms were performed in all specimens and in preparations with resin/lead power additional three dimensional reconstructions of the surface of the acetabulum and arterial cast were done with 3D-CT. 3D-CT shows precise relationship of the arteries to the acetabulum in any spatial plane and definition of vascular supply without elaborate preparation. 3D-CT is superior to non-selective conventional angiography because of better definition of arterial arborization. Filling with resin and lead powder is optimal for anatomical studies because of its reliability and stability. It permits comparative 3D-CT and conventional x-ray examination and subsequent preparation of the vessels in corrosion technique. The advantages of 3D-CT in vessels of cadaver specimens should encourage research on its viability in patients. PMID- 8453075 TI - [Morphological changes of the lower leg arteries and the plantar arch in diabetic and nondiabetic patients with chronic critical ischemia of the leg]. AB - In this prospective study we evaluated if atherosclerosis of crural and pedal arteries differs in diabetic and non-diabetic patients suffering from chronic ischemia. We performed intraoperative angiography after completion of a femoro popliteal or femoro-distal bypass. No statistically significant difference was found between the two groups (25 diabetic and 44 non-diabetic patients) concerning the severity and localisation of the arteriosclerosis in the three crural arteries and the pedal arch. The prerequisite for a successful arterial reconstruction were identical in our patients with or without diabetes and a similar number of potential recipient arteries were found at below knee and foot level in both groups. PMID- 8453076 TI - [Real-time flow--determination of inferior vena cava on 2 different levels using RACE pulse sequence in MRI. Assessment of the total hepatic vein flow volume as an indirect parameter of liver perfusion]. AB - A new and simple parameter for quantitative evaluation of liver perfusion is outlined: post-sinusoidal quantitative measurement of the entire liver venous flow: This is a result of the differences in evaluated flow volumes at two different levels in the inferior V. cava. The first level ist the height of diaphragm, and the second is situated just cranial of the renal vessels. Normal values obtained from a group of healthy volunteers are presented. A gradient-echo pulse sequence called RACE, enabling flow measurements in real-time, is outlined. PMID- 8453077 TI - [Retrograde venous occlusion--therapy of impotence of venous origin]. AB - Retrograde occlusion of penile drainage veins can produce improvement in patients with impotence due to venous leaks. We performed 50 transfemoral and three transjugular procedures; 46 (86%) were technically successful. Clinical improvement was found in 24 out of the 46 procedures (52%). In 20 patients spontaneous intercourse became possible, in four this occurred after intracavernous injection of vaso-active substances. In eleven patients there was deterioration after one to twenty months; in seven this was treated by repeated venous occlusion. In 13 patients improvement has been maintained over a period of one to thirty months (average 10.5 months). There were no complications. PMID- 8453078 TI - [Experimental studies of the pressure stability of vascular endoprostheses]. AB - Percutaneously implantable vascular prostheses used clinically (Strecker, Palmaz and Wall stents) were tested as realistically as possible with regard to their mechanical stability. The Palmaz stent showed the greatest pressure stability. Even at pressures above three atmospheres the stent remained within 20% of its nominal diameter. In contrast, the Wall and Strecker stents showed much less pressure stability. Depending on the diameter of the wire and of the stent, there was 20% reduction in diameter at pressures between 0.13 and 0.68 atmospheres. These results will contribute to an improved application of the vascular endoprostheses which have been tested. PMID- 8453079 TI - [Ingestive contrast medium (sonographics) in abdominal ultrasonography. In-vitro and in-vivo studies]. AB - In-vitro tests of new ingestive contrast media (known as "sonographics") are reported. A catalogue comprising 6 points for standards of an "ideal" sonographicum is outlined by systematic comparison to echogenicity of liver parenchyma in n = 49 healthy persons. Preliminary clinical tests show significant improvement of diagnostics in the upper abdomen; however problems do exist in the evaluation of these contrast media, too: Different echogenicities of sonographics can serve variable aims in diagnostic ultrasonography. Simultaneous application of several transducers may enable complete cross-sections of the human torso as in CT, based on further evaluation of ingestive contrast media. PMID- 8453080 TI - [CT contrast administration of iodine, gadolinium and ytterbium. In-vitro studies and animal experiments]. AB - The absorption of the elements iodine, gadolinium and ytterbium in various dilutions was studied in relation to CT. Regression analysis and specific CT density measurements showed that absorption decreases from gadolinium to ytterbium and iodine. These results were confirmed by experiments using ten dogs. Boli of 0.5 molar gadolinium used for angio-CT without table movement showed the largest increase in density in the aorta and liver with an average of 190HU and 21HU respectively compared with iodine which gave 157HU and 12HU respectively. The animal experimental studies suggest that gadolinium and ytterbium are suitable contrast media for dynamic CT investigations. PMID- 8453081 TI - [Turbo(fast) spin echo at 0.5 T: effect of echo distance and echo number on image contrast]. AB - Signal intensities, signal-to-noise ratios (S/N), and contrast-to-noise ratios (C/N) in dependence on the echo distance and echo number of the new turbo (fast) spin-echo technique are analysed by phantom, volunteer and patient measurements. With increasing echo number (3 to 15 echoes), signal intensities increase (25 to 50%), S/N varies between different tissues, and C/N of fat to water decreases (70%). A high echo number, although it shortens the imaging time, is thus not always the best choice since the fat/water contrast is lost. However, a high fat/water contrast is advantageous for several MR applications. PMID- 8453082 TI - [Absorption properties of supporting tissues in low-energy molybdenum spectrum as basis for a material-qualitative roentgen image in mixed color coding]. AB - The absorption properties of bone and cartilage tissue in the molybdenum spectrum are studied firstly according to Bragg and secondly by means of radiographs taken with different sections of the spectrum, revealing differences substance specifically dependent on the radiation frequency. These differences can be utilised for imaging by means of substance-specific color-coded radiography. PMID- 8453083 TI - [Selective angiography using 3-F catheters. Technique using molded hydrophilic coated mandrins]. PMID- 8453084 TI - [Use of the rotablator in the therapy of diabetic macroangiopathies of the lower leg--initial experiences]. PMID- 8453085 TI - Bilateral pelvic digits. A case report and review of the literature. PMID- 8453086 TI - [MR tomography in mobile odontoid process]. PMID- 8453087 TI - [Precocious puberty and gelastic epilepsy in hamartoma of the tuber cinereum]. PMID- 8453088 TI - [Serous-papillary cystadenocarcinoma of the ovary: problems in the CT identification of calcified intraperitoneal metastases]. PMID- 8453089 TI - Platelet transfusions: the 20,000/microL trigger. PMID- 8453090 TI - Lowest dose interleukin-2 immunotherapy. PMID- 8453091 TI - Inactivation of interleukin-8 by the C5a-inactivating protease from serosal fluid. AB - The complement fragment C5a and the cytokine interleukin-8 (IL-8) are proinflammatory peptides with potent chemotactic activity toward neutrophils. We have previously shown that C5a can be inactivated by a protease that is found in normal synovial and peritoneal fluids but is absent from serosal fluids obtained from patients with familial Mediterranean fever (FMF). We report here that serosal fluids can also eliminate the chemotactic activity of IL-8. The agent responsible for IL-8 elimination appears to be the C5a-inactivating protease, because the pure protease can inactivate IL-8, inactivation of IL-8 by normal peritoneal fluid is partly prevented by an antibody raised against the purified C5a-inactivating protease, and IL-8 is not inactivated by peritoneal fluids from patients with FMF. The ability of this protease to inactivate both, early (C5a) and late (IL-8) inflammatory mediators identifies it as a potentially significant regulator of inflammation. PMID- 8453093 TI - Cascade transactivation of growth factor receptors in early human hematopoiesis. AB - Highly purified progenitors (including erythroid [BFU-E], granulo-monocytic [CFU GM], multipotent [CFU-GEMM] progenitors, as well as multipotent progenitors with self-renewal capacity [CFU-B]) express high-affinity growth factor receptors (GFRs), with prevalent interleukin-3 receptors (IL-3Rs) (2,700/cell), a > or = 10 fold lower number of IL-6Rs (145/cell) and granulocyte-macrophage colony stimulating factor receptors (GM-CSFRs) (300/cell), and a barely detectable level of erythropoietin (Ep) receptors (75/cell). Hematopoietic growth factor (HGF) dosages inducing peak clonogenetic effects are associated with partial/subtotal occupancy of the homologous HGF receptor (HGFR). Cross-reactivity between GFRs and heterologous GFs (including IL-6, IL-3, GM-CSF, Ep, and the kit ligand [KL]) was explored by competition experiments on purified progenitors with radiolabeled and excess cold HGFs at +4 degrees C. No cross-reaction was observed between IL 6R, IL-3R, EpR, and the heterologous GFs, whereas the GM-CSFR showed cross reactivity with IL-3 and, to a lesser extent, KL. Modulation of GFRs was examined after 18 or 40 hours of incubation with GF(s) at 37 degrees C, followed by ligand binding assay at 20 degrees C. IL-6, IL-3, GM-CSF, and Ep induce a marked down modulation of their own receptors. Interestingly, each GF induces the transactivation of the R(s) for the "distal" GF(s): (1) IL-6 induces transactivation of IL-3R, but not of GM-CSFR/EpR; (2) IL-3 causes a rapid upmodulation of GM-CSFR/EpR ("pure" progenitors treated with IL-3 show upmodulation of GM-CSFR alpha-chain mRNA by reverse transcriptase-polymerase chain reaction); whereas (3) GM-CSF induces the transactivation of the EpR. This chain upmodulation of HGFRs may underlie the synergistic interactions between the HGFs in clonogenetic culture. It is emphasized that KL does not induce upmodulation of the other GFRs. Finally, Ep, GM-CSF, and IL-3 do not modulate the expression of the "proximal" HGFRs (ie, GM-CSFR/IL-3R/IL-6R, IL-3R/IL-6R, and IL 6R, respectively). These results allow insight into the cellular basis of hematopoiesis, ie, the complex and coordinate interactions between HGFs and their receptors. They are compatible with a model of cascade transactivation via upmodulation of GFRs in the initial key steps of hematopoietic differentiation, whereby the action of each GF enhances the effect of the distal GF(s) by a multistep chain-potentiation mechanism. PMID- 8453092 TI - Natural interferon-alpha in combination with melphalan/prednisone versus melphalan/prednisone in the treatment of multiple myeloma stages II and III: a randomized study from the Myeloma Group of Central Sweden. AB - Three hundred thirty-five previously untreated patients with multiple myeloma in clinical stages II and III entered a randomized trial comparing intermittent oral melphalan and prednisone (MP) therapy (n = 171) with MP in combination with natural (leukocyte-derived) alpha-interferon (MP/IFN) (n = 164). The treatment groups were comparable with regard to major prognostic factors. The response frequency was 42% in the MP group and 68% in the MP/IFN group (P < .0001). Eighty five percent of IgA myelomas and 71% of Bence-Jones myelomas responded to MP/IFN compared with 48% and 27%, respectively, to MP treatment (P = .001). There was no difference in the overall survival between the two treatment groups. However, the survival of 72 patients with IgA or Bence-Jones myeloma randomized to receive MP/IFN was significantly longer (median 32 months) than that of 71 patients treated with MP (median 17 months) (p < .05). No statistically significant difference in response frequency (60% v 46%) or survival was found for patients with IgG myeloma. Hematologic toxicity, WHO grades III and IV, was higher in the MP/IFN group (48%) than in the MP group (33%) (P < .05) during the induction treatment period. Flulike syndrome was observed in 68% of patients receiving MP/IFN. The results show that MP/IFN is a well-tolerated treatment regimen, superior to MP for remission induction, and it improves significantly the overall survival for patients with IgA and Bence-Jones myelomas. PMID- 8453094 TI - Epidemiology of aplastic anemia in France: a case-control study. I. Medical history and medication use. The French Cooperative Group for Epidemiological Study of Aplastic Anemia. AB - Aplastic anemia (AA) is a rare, severe disease of mainly unknown origin. Numerous case history reports have incriminated drugs in the etiology of this disease. Because those reports were questionable, a case-control study was conducted in France between 1985 and 1988. Cases selected from the national register were eligible for inclusion when at least two blood lineages were depressed (hemoglobin < or = 10 g/100 mL and reticulocytes < or = 50 x 10(9)/L, granulocytes < or = 1.5 x 10(9)/L, platelets < or = 100 x 10(9)/L) and when the bone marrow biopsy was compatible with the disease. Using a standardized questionnaire, trained investigators interviewed one AA patient and two groups of controls (two hospitalized patients and one neighbor of the AA patient) matched for age, sex, and interviewer. One hundred forty-seven AA patients, 287 hospitalized controls, and 108 neighbors were interviewed. The occurrence of AA was analyzed by matched design with relation to medical history and drug use during the last 5 years, and specifically during the last year. Three times as many AA patients reported having suffered from clinical hepatitis during the last 6 months than either type of control. Similarly, a higher proportion of AA patients reported a history of chronic immune disorder, mainly rheumatoid arthritis (odds ratio of 6.8), and a previous use of gold salts and D penicillamine in the 5 previous years (odds ratio of 4.9 for each drug). An excess of colchicine and allo/thiopurinol intake in the 5 previous years was observed among the AA patients (odds ratio equal to 4.1 and 3.6, respectively). These results for gold salts, D-penicillamine, and colchicine were confirmed when looking for drug use within the last year. A moderate risk was associated with acetaminophen or salicylate intake during the 5 previous years or during the last year (odds ratio between 1.8 and 2.0). The frequent use of salicylates within the last year was associated with a high risk of AA (odds ratio of 5.0). A high risk was also associated with indolic derivative intake but only when comparing AA patients to neighbor controls. No association could be evidenced with diclofenac intake, whatever the control group. Differences observed with recently published studies suggest that targeted studies on each category of drugs according to the treated pathologies should be initiated. PMID- 8453095 TI - Purified murine hematopoietic stem cells function longer on nonirradiated W41/Wv than on +/+ irradiated stroma. AB - Mouse bone marrow (BM) was separated into low-density, lineage-negative, wheat germ agglutinin-positive (WGA+), Rhodamine-123 bright (Rhbright) or dim (Rhdim) cells to obtain populations that were highly enriched for committed progenitors (Rhbright cells) or for more primitive stem cells (Rhdim). When 2,500 Rhbright or Rhdim cells were seeded onto 6-week-old irradiated (20 Gy) long-term BM cultures (LTBMC), the nonadherent cell production from Rhbright cells was transient and ended after 5 weeks. Production from Rhdim cells did not begin until week 3, peaked at week 5, and ended at week 8, when the irradiated stroma seemed to fail. Termination of cell production from Rhdim cells did not occur in nonirradiated LTBMC from W41/Wv mice. During peak nonadherent cell production, 25% to 30% of the cells in the nonirradiated LTBMC from W41/Wv mice had donor cell markers. Two approaches were tested to try to enhance the proportion or number of donor cells. Addition of Origen-HGF at the time of seeding Rhdim cells caused a nonspecific increase in both host and donor cell production, but a specific increase in production of donor cells was obtained by seeding the cultures at 2 weeks rather than 6 weeks. Limiting dilution of Rhdim cells gave the same frequency of wells producing cells on both irradiated +/+ and nonirradiated W41/Wv or W/Wv cultures. PMID- 8453096 TI - Use of 5-fluorouracil to analyze the effect of macrophage inflammatory protein-1 alpha on long-term reconstituting stem cells in vivo. AB - A macrophage-derived inhibitor of early hematopoietic progenitors (colony-forming unit-spleen, CFU-A) called stem cell inhibitor was found to be identical to macrophage inflammatory protein-1 alpha (MIP-1 alpha). We investigated the effect of MIP-1 alpha on the earliest stem cells that sustain long-term hematopoiesis in vivo in a competitive bone marrow repopulation assay. Because long-term reconstituting (LTR) stem cells are normally quiescent, an in vivo model was first developed in which they are triggered to cycle. A first 5-fluorouracil (5 FU) injection was used to eliminate later progenitors, causing the LTR stem cells, which are normally resistant to 5-FU, to enter the cell cycle and become sensitive to a second 5-FU injection administered 5 days later. Human MIP-1 alpha administered from day 0 to 7 was unable to prevent the depletion of the LTR stem cells by the second 5-FU treatment, as observed on day 7 in this model, suggesting that the LTR stem cells were not prevented from being triggered into cycle despite the MIP-1 alpha treatment. However, the MIP-1 alpha protocol used here did substantially decrease the number of more mature hematopoietic progenitors (granulocyte-macrophage colony-forming cells [CFC], burst-forming unit-erythroid, CFCmulti, and preCFCmulti) recovered in the bone marrow shortly after a single 5-FU injection. In vitro, MIP-1 alpha had no inhibitory effect on the ability of these progenitors to form colonies. This study confirms the in vivo inhibitory effect of MIP-1 alpha on subpopulations of hematopoietic progenitors that are activated in myelodepressed animals. However, MIP-1 alpha had no effect on the long-term reconstituting stem cells in vivo under conditions in which it effectively reduced all later progenitors. PMID- 8453097 TI - Membrane glycoproteins and platelet cytoskeleton in immune complex-induced platelet activation. AB - To clarify the mechanism of platelet activation by immune complexes and the possible involvement of surface glycoproteins (GPs), we studied platelet activation induced by heat-aggregated IgG (HAG). We examined the effects of monoclonal antibodies (MoAbs) against GPIb, GPIIb/IIIa, and the Fc receptor on resting platelets and on platelets stimulated by HAG. HAG increased the cytosolic ionized calcium concentration ([Ca2+]i) and stimulated protein (P47 and P20) phosphorylation, phosphatidic acid (PA) synthesis, serotonin secretion, and platelet aggregation. IV.3, an anti-Fc gamma RII receptor MoAb, inhibited HAG binding to platelets and all subsequent platelet responses. Like IV.3, MoAbs against GPIIb/IIIa (Tab, 10E5, AP-3) or GPIb (AP-1, 6D1) strongly inhibited platelet activation by HAG. However, while anti-GPIIb/IIIa MoAbs inhibited binding of IV.3 and HAG to platelets, anti-GPIb MoAbs had little effect on platelet binding of IV.3 or HAG. These observations suggest a close topographical and functional association of GPIIb/IIIa with Fc gamma RII in the platelet response to HAG. Cytochalasin B, an inhibitor of actin polymerization, also inhibited platelet activation but not HAG or IV.3 binding. Measurement of the fluorescence of 7-nitrobenz-2-oxa-1,3-(NBD)-phallacidin, a specific marker for filamentous actin (F-actin), showed that both cytochalasin B and AP-1 blocked the increase of F-actin induced by HAG. The common effects of anti-GPIb MoAbs and of cytochalasin B suggest that unlike the activity of GPIIb/IIIa, the ability of anti-GPIb to inhibit the activation of platelets by immune complexes is associated with perturbation of the cytoskeleton. PMID- 8453098 TI - Use of porcine factor VIII in the treatment of patients with acquired hemophilia. AB - Data have been collected from 47 centers in Europe and North America on the treatment with porcine factor VIII concentrate of 74 acute bleeding episodes in 65 patients with acquired hemophilia. The median initial anti-human factor VIII auto-antibody inhibitor level was 38 Bethesda unit (BU)/mL (range 1.2 to 1,024) whereas that against porcine was 1 BU/mL (range 0 to 15). The mean initial dose of porcine factor VIII infused was 84 IU/kg, which increased the plasma factor VIII:C activity by 0.85 IU/mL. Therapy was continued for a mean of 8.5 days during which time the average number of infusions was 11. Objective clinical responses were rated as good or excellent in 78% of recipients. Side effects were uncommon; only one patient experienced a severe anaphylactic reaction necessitating the discontinuation of porcine FVIII therapy. After therapy, no increase in the median level of anti-human FVIII or anti-porcine antibody was noted in the group as a whole, although 13 patients showed individual increases in either anti-human or anti-porcine antibody levels or both of more than 10 BU/mL. Of the 7 patients who subsequently rebled, 5 were successfully re-treated and 2 did not respond to further porcine factor VIII treatment. Porcine factor VIII is safe and clinically effective treatment for bleeding episodes associated with acquired hemophilia and should be considered as first-line therapy for patients whose acquired anti-factor VIII:C antibody cross-reacts with porcine factor VIII:C at low levels. PMID- 8453099 TI - Acute infectious mononucleosis stimulates the selective expression/expansion of V beta 6.1-3 and V beta 7 T cells. AB - Acute infectious mononucleosis (AIM) is caused by the Epstein-Barr virus (EBV) and is characterized by a proliferation of atypical lymphocytes, predominantly CD8+ T cells. Various diseases associated with T-cell activation have been shown to stimulate the selective expansion of certain V beta (variable region of the T cell receptor beta chain) expressing T-cell populations. The purpose of this investigation was to determine if the proliferation of T cells accompanying AIM is associated with selective expression/expansion of distinct populations of V beta T cells. We determined V beta expression in eight patients with clinical and laboratory evidence of AIM, including an atypical lymphocytosis. Gel electrophoresis and quantitative analysis were performed on cDNA amplified by the polymerase chain reaction (PCR) using different V beta region primers. Gel electrophoresis analysis showed prominent V beta 6.1-3 and V beta 7 bands in all eight patients with AIM but not in the controls. Quantitative PCR analysis showed that the V beta 6.1-3 and V beta 7 mean PCR ratios increased, respectively, from 163.0 +/- 22.5 and 142.3 +/- 5.5 in controls to 339.9 +/- 38.8 (P < .03) and 396.1 +/- 45.6 (P < .01) in the eight patients with AIM. Two of the eight patients who had increased V beta 6.1-3 and V beta 7 expression were retested after clinical resolution of AIM and no longer had evidence of increased V beta 6.1-3 and V beta 7 T-cell expression. AIM is associated with a selective increased expression of V beta 6.1-3 and V beta 7 T cells present at the time of initial clinical symptoms and atypical lymphocytosis. This increased expression resolves following recovery from AIM. This V beta-specific selective expression resembles the super-antigen response seen after staphylococcal toxin stimulation and may be caused by EBV triggering of selective expansion of V beta 6.1-3 and V beta 7 T-cell subsets. PMID- 8453100 TI - Tyrosine phosphorylation of guanosine triphosphatase activating protein by activation via surface IgG in human B cells. AB - In this study, we analyzed tyrosine phosphorylation of guanosine triphosphatase (GTPase) activating protein in human B cells stimulated through surface IgG, using Western blot and immunoprecipitation. Stimulation through surface IgG induced the tyrosine phosphorylation of GTPase-activating protein (GAP) and two associated proteins, a 190-Kd protein and a 62-Kd protein, within 1 minute and in a dose-dependent manner. This tyrosine phosphorylation was blocked by Genistein (Extrasynthese, Genay, France). These data suggest that GTPase-activating protein is involved in a signal transduction pathway initiated from surface IgG in human B cells. PMID- 8453101 TI - Regulation of c-jun gene expression in human T lymphocytes. AB - The present studies have examined the effects of mitogens on induction of early response gene expression in normal peripheral blood T and Jurkat cells. Pokeweed mitogen (PWM) or anti-CD3 significantly increases c-jun messenger RNA (mRNA) levels in T cells. This transient PWM-related increase in c-jun transcripts is maximal after 15 to 30 minutes of exposure of T cells to PWM. PWM induces c-jun gene expression in a concentration-dependent manner. Moreover, PWM similarly induces expression of other genes coding for leucine zipper transcription factors, ie, jun-B and c-fos. Nuclear run on assays demonstrate that PWM treatment is associated with an increased rate of c-jun gene transcription. Transient expression assays with c-jun promoter fragments linked to the chloramphenicol acetyltransferase gene suggest that the PWM-induced increase in transcription is mediated by the AP-1 transcription factor complex. Moreover, treatment of T cells with actinomycin D to block further transcription before their culture with PWM suggests that the increase in c-jun gene expression by PWM is also regulated at least in part by a posttranscriptional mechanism. Cycloheximide does not alter c-jun mRNA induction by PWM. Finally, given that PWM induces B-cell differentiation in an interleukin-6 (IL-6)-mediated, T-cell dependent manner, the relationship of c-jun and IL-6 gene expression in PWM stimulated T cells was examined. The induction of IL-6 mRNA in T cells stimulated by PWM occurs after maximal induction of c-jun mRNA, at a time when the latter is no longer detectable. These findings suggest that PWM induces c-jun gene expression in T cells by a transcriptional and posttranscriptional mechanism and that AP-1 confers PWM inducibility of this gene. Because the IL-6 promoter has several potential transcriptional control elements, one of which is an AP-1 binding site, future experiments will evaluate the role of c-jun in the regulation of PWM-induced IL-6 synthesis by T cells. PMID- 8453102 TI - Duplication of small segments within the major breakpoint cluster region in chronic myelogenous leukemia. AB - The t(9;22) in chronic myelogenous leukemia (CML) may be reciprocal or, in a minority of cases, may result in an extensive deletion of a portion of the major breakpoint cluster region (M-bcr) of the BCR. This report provides evidence of the duplication of small segments within the M-bcr in a small group of patients with CML. Southern blots of Bgl II and Bgl II/BamHI double-digested DNA from the blood or bone marrow of 46 patients with CML were probed with a 5' 1.4-kb Taq I/HindIII M-bcr probe and a 3' 2-kb HindIII/BamHI M-bcr probe. In three patients, rearrangements were noted with both probes in Bgl II-digested DNA, but were not present in Bgl II/BamHI-digested DNA with either probe. Southern analysis of DNA samples double-digested with Bgl II and BspHI from two of these three cases showed no rearrangements with either probe; the M-bcr BspHI site is located 26 bp 3' of the BamHI site in the second intron of the M-bcr. The presence of a rearranged M-bcr with both probes in Bgl II-digested DNA and the lack of rearrangement in Bgl II/BamHI and Bgl II/BspHI double-digested DNA suggest the presence of M-bcr BamHI and BspHI sites on both 9q+ chromosome (9q+) and the Philadelphia chromosome (Ph). This implies a duplication of at least the 26-bp M bcr BamHI/BspHI fragment in these two samples. Sequence data from one of these two cases confirmed the M-bcr breakpoints to be staggered; the Ph M-bcr breakpoint occurred 258 bp downstream from the 9q+ M-bcr breakpoint. It is concluded that a duplication of small segments within the M-bcr occurs in a small group of patients with CML, which may lead to pseudogermline patterns on Southern blot. Such a duplication may provide insight into the mechanism of some chromosomal translocations in neoplasia. PMID- 8453103 TI - The 8;21 chromosome translocation in acute myeloid leukemia is always detectable by molecular analysis using AML1. AB - The AML1 gene was rearranged in leukemic cells with t(8;21)(q22;q22) or its variant, complex t(8;V;21) translocations from 33 acute myeloid leukemia (AML) patients. The AML1 rearrangement was also detected in three AML patients without t(8;21); two had a normal diploid karyotype, and one had a karyotype of 45,X, - X. The AML1 rearrangement in the t(8;21) breakpoint cluster region was not detected in leukemic cells with cytogenetic abnormalities other than t(8;21), or with normal diploidy obtained from 23 AML patients. Because leukemic cells of the five patients with complex t(8;V;21) translocations had a der(8)t(8;21) chromosome with a break in band 8q22 in common, the juxtaposition of the 5' side of AML1 to a predicted counterpart gene located in the breakpoint region of 8q22 may be an essential step in the leukemogenesis of AML with t(8;21). Our findings show that the 8;21 translocation, its variants, and the masked t(8;21) may all be detectable by the Southern hybridization method using the AML1 probes. PMID- 8453104 TI - Cytogenetic clonality in myelodysplastic syndromes studied with fluorescence in situ hybridization: lineage, response to growth factor therapy, and clone expansion. AB - Clonality in myelodysplastic syndromes (MDS) has been studied with various techniques including glucose-6-phosphate dehydrogenase (G6PD) isoenzyme and cytogenetic analyses, and with molecular techniques such as gene deletion studies and the analysis of restriction fragment-length polymorphisms (RFLP) of X-linked genes. In this study, we investigated the use of fluorescence in situ hybridization (FISH) with a chromosome-specific probe to examine cytogenetic clonality in peripheral blood (PB) cells from three patients with MDS. In each case, trisomy 8 was shown by conventional cytogenetic analysis at the time of the initial diagnosis. By using FISH with a probe for the centromere of chromosome 8, we identified the trisomy in individual PB cells from Wright-stained smears. With this technique, we could determine the cell lineage involved by the trisomy, and through serial analyses we could assess the response of the clonal and nonclonal cells to growth-factor therapy, and the expansion of the trisomic clone over time. In each of the three cases, various proportions of granulocytes, monocytes, eosinophils, and basophils showed trisomy 8 by FISH analysis. In none of the cases did we detect trisomy 8 in lymphocytes. By analysis of PB cells before and during therapy with recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF), we found that GM-CSF stimulated both trisomic and disomic cells. During a 1-year period of sequential study, we detected an abrupt increase in the percentage of trisomic cells in one patient, a stable percentage in another, and a slowly increasing percentage in the third. The abrupt increase in the first patient preceded a transformation to a more acute phase by 2 months. We conclude that FISH analysis of PB cells of patients with MDS offers an additional approach to the study of clonality in this disorder. In some cases this analysis may provide a useful and simple means of assessing response to therapy and progression of disease. PMID- 8453105 TI - Effects of interleukin-11 on the proliferation and cell cycle status of myeloid leukemic cells. AB - Interleukin-11 (IL-11) is a pleiotropic cytokine with effects on many different targets. Within the hematopoietic system, the effects of IL-11 are largely manifest only through combination with other cytokines, including IL-3 and Steel factor (SF). In the present study, we addressed the question of IL-11 responsiveness within the different types of human leukemic cells, as well as the mechanism of action of IL-11 at the cellular level. Analysis of a panel of samples from different patients with acute myeloblastic leukemia (AML) and myeloid leukemic cell lines indicated that IL-11 alone was ineffective in supporting myeloid leukemic cell growth but frequently enhanced growth supported by IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), or SF. In contrast, three acute pre-B lymphocytic leukemia (pre-B-ALL) and two acute T lymphocytic leukemia (T-ALL) lines failed to respond to IL-11 alone or when combined with other cytokines. The growth enhancement of IL-11 among the AML patient samples was dose dependent and remarkably constant with half-efficient concentrations in the range of 0.3 to 0.4 ng/mL. The thymidine suicide studies with the patient samples revealed that 40% to 50% of the blast cells were in S phase when exposed for 16 hours to IL-3 and this level was increased to 70% to 90% in response to either IL-11 or IL-6. Our data suggest that the latter two interleukins act synergistically with the direct mitogenic factor, IL-3, in triggering AML blast-cell proliferation. Detailed analysis with several patient samples further revealed that SF and IL-11 both enhance IL-3-supported clonogenic growth of AML blasts and the combination of all three growth factors yields optimal growth. In contrast, IL-6 does not further enhance the effect of IL-11. These results indicate that SF and IL-11 enhance IL-3-dependent clonogenic growth through two distinct pathways, whereas IL-6 and IL-11 may trigger the same pathway. PMID- 8453106 TI - Erythropoietin synthesis by tumor cells in a case of meningioma associated with erythrocytosis. AB - While secondary erythrocytosis is often associated with tumors arising from the kidney, other tumors have been described to originate in the liver, uterus, ovary, adrenal gland, and central nervous system, among which cerebellar hemangioblastomas are involved in most instances. Two cases of meningioma associated with erythrocytosis have already been reported. We observed a 59-year old female patient who had developed a frontal meningioma associated with erythrocytosis. Before surgery, she had a significantly elevated total red blood cell volume with a normal plasma volume. Serum erythropoietin (Epo) dosage assessed by radioimmunoassay was within the normal range. The tumor was removed and the pathologic study found a meningotheliomatous meningioma. Total RNA from the tumor was hybridized to a monkey cDNA Epo probe. A strong 1.6-kb messenger RNA (mRNA) signal was observed, which is the expected size of human Epo mRNA. In situ hybridization with the 35S-labeled Epo probe was performed on frozen tumor tissue sections. A significant hybridization was observed in all the tumor cells, whereas the stroma was negative. Therefore, in this meningioma associated with erythrocytosis, Epo was produced by the tumor cells themselves. PMID- 8453107 TI - In vitro infection of human macrophages with human T-cell leukemia virus type 1. AB - The tropism of the human T-cell leukemia virus type 1 (HTLV-1) for the cells of monocyte-macrophage lineage was evaluated by the coculture of blood monocyte derived macrophages, with irradiated cells of HTLV-1 producing cell lines MT2 or C91/PL. The susceptibility to HTLV-1 was assessed by the detection of viral DNA using the polymerase chain reaction method. HTLV-1 gene expression in the cells was detected using in situ hybridization and by immunofluorescent staining of viral antigen. The presence of type C virus-like particles detected by electron microscopy and the ability to infect normal cord blood lymphocytes demonstrated that the infected macrophages produced infectious virus. These results indicate that human macrophages are susceptible in vitro to productive HTLV-1 infection, and thus might be involved in the pathogenesis of HTLV-1-related diseases. PMID- 8453108 TI - Molecular cloning, chromosomal location, and tissue-specific expression of the murine cathepsin G gene. AB - We previously have characterized a cluster of genes encoding cathepsin G (CG) and two other CG-like hematopoietic serine proteases, CGL-1 and CGL-2, on human chromosome 14. In this report, we clone and characterize a novel, related murine hematopoietic serine protease gene using human CG (hCG) cDNA as the probe. This murine gene spans approximately 2.5 kb of genomic DNA, is organized into five exons and four introns, and bears a high degree of homology to hCG at both nucleic acid (73%) and deduced amino acid (66%) levels. The predicted cDNA contains an open reading frame of 783 nucleotides that encodes a nascent protein of 261 amino acids. Processing of a putative signal (pre) peptide of 18 residues and an activation (pro) dipeptide would generate a mature enzyme of approximately 27 Kd that has an estimated pI of 12.0. Conserved residues at His44, Asp88, and Ser181 form the characteristic catalytic triad of the serine protease superfamily. The gene is tightly linked to the CTLA-1 locus on murine chromosome 14, where the serine protease genes mCCP1-4 are clustered. Expression of this gene is detected only in the bone marrow and is restricted to a small population of early myeloid cells. These findings are consistent with the identification of the gene encoding murine CG. PMID- 8453110 TI - Autologous bone marrow transplantation after a long first remission for children with recurrent acute lymphoblastic leukemia. AB - Fifty-one children with acute lymphoblastic leukemia (ALL) in second or subsequent remission after a first remission of at least 24 months underwent purged, autologous bone marrow transplantation (ABMT). Bone marrow was harvested in remission and purged in vitro with monoclonal antibodies specific for leukemia associated antigens. Ablative chemotherapy included cytarabine, teniposide, and cyclophosphamide followed by total body irradiation. Of the 51 patients treated between November 1980 and June 1991, 5 died of treatment-related complications, 18 relapsed, 1 died of a second tumor at 6.7 years, and 27 remained in continuous complete remission for a median of 39 months (range, 9+ to 124+). Event-free survival (EFS) (+/- SE) at 3 years after ABMT was 53% +/- 7%. Leukemia-free survival (LFS) was 58% +/- 8%. In multivariate analysis, the most significant predictors of EFS were duration of longest pre-ABMT remission and remission duration immediately before ABMT. For LFS, the most significant predictors were cell dose per kilogram of marrow reinfused and duration of longest pre-ABMT remission. We conclude that ABMT for this population is an effective therapy available to the majority of children with relapsed ALL. PMID- 8453109 TI - Human T-cell leukemia virus type II infection frequently goes undetected in contemporary US blood donors. AB - Serologic screening for human T-cell leukemia virus type I (HTLV-I) infection was begun in US blood banks with the licensure of enzyme-linked immunosorbent assays (ELISA) in December 1988. We examined the donation histories of the first 60 Western blot (WB)-confirmed HTLV-I/II positive donors to one blood center and found 8 had made 16 previous donations that scored negative on the screening ELISA. All 16 donations had ELISA absorbance below the cutoff for a positive assay, but still well above that of the average donation (17.6% +/- 5.7% of the cutoff). In a more extensive study, 17 donations from a total of 61,752 at six blood centers were both ELISA-positive and WB-positive for HTLV-I (4) or HTLV-II (13), and 218 samples had ELISA absorbance greater than 50% of the ELISA cutoff. One hundred seventy-eight of the 218 were tested further by WB and 11 were found positive. All 11 positives were confirmed by polymerase chain reaction; 10 had HTLV-II and 1 had HTLV-I. Thus, the HTLV-I-based screening ELISA missed at least 10 of 23, or 43% (95% confidence interval, 23% to 66%), of HTLV-II infections, compared with 1 of 5, or 20%, of HTLV-I infections. PMID- 8453111 TI - Prevention of graft-versus-host disease and bone marrow rejection: kinetics of induction of tolerance by UVB modulation of accessory cells and T cells in the bone marrow inoculum. AB - UVB irradiation (700 J/m2) of bone marrow cells (UVB-BMC) before transplantation into lethally gamma-irradiated (10.5 Gy) allogeneic rats prevents graft-versus host disease (GVHD) and induces a stable complete lymphohematopoietic chimerism. To better understand the underlying mechanism of the development of stable chimerism and induction of tolerance to donor organs in this model, we examined if the addition of T cells or dendritic cells (DC), as antigen presenting cells (APC), would restore the immunogenicity of UVB-BMC in in vitro mixed lymphocyte reaction (MLR) and induce in vivo bone marrow (BM) graft rejection. Whereas gamma irradiated, unfractionated BMC induce allogeneic T cells to proliferate, UVB irradiation of BMC abolishes the stimulatory capacity of such cells in a primary MLR. Addition of purified T cells, CD4+ T cells, CD8+ T cells or B cells, respectively, failed to restore the capacity of UVB-BMC to stimulate allogeneic T cell proliferation. In contrast, the addition of only a small number of splenic accessory cells or purified DC, which by themselves were relatively ineffective in stimulating T-cell proliferation, restored the accessory function and the allostimulatory capacity of UVB-BMC. To define the molecular defect induced by UVB irradiation, cytokines were added as costimulatory factors to primary MLRs and the results showed that the addition of interleukin (IL)-2 or IL-6 but not IL 1 or interferon gamma (IFN-gamma) restored the stimulatory capacity of UVB BMC. This finding suggests that UVB may alter the production, and/or utilization of IL 2 and IL-6 either at the membrane or cytoplasmic level. Parallel in vivo studies showed that addition of DC to UVB BM inoculum resulted in failure of BM engraftment, whereas addition of T cells led to development of fatal GVHD, thus suggesting that UVB modulation of accessory cells reduces graft immunogenicity and prevents BMT rejection, while modulation of T cells prevents GVHD. Our data provide evidence that UVB modulation of APC and mature T cells contained within BMC is potentially useful in preventing GVHD without endangering successful engraftment and may serve as a model for induction of adult chimerism and tolerance without the development of GVHD. PMID- 8453112 TI - Kinetics of hemoglobin synthesis in mice and humans. PMID- 8453113 TI - [Effect of therapeutic exercise on physical fitness in a school health program for obese children]. AB - The objectives of this study were to determined characteristics of physical fitness in obese children, and to examine the effect of a diet-exercise program, developed in our laboratory, on the physical fitness of these children. To accomplish the first objective, a physical fitness test consisting of 11 items was administered on 126 obese and normal weight children (boys 83, girls 43) matched for age, sex, and stature. The children, 9-10 years of age, were pupils from 11 public elementary schools in Morioka, Iwate, Japan. To accomplish the second objective, 92 obese children participated in a study. The children were divided into experimental and control groups. Children in the experimental group (n = 50) participated in a diet-exercise program for three months, while children in the control group (n = 42) were left alone without taking part in the program. The results of this study are summarized as follows; 1. The obese children were found to be significantly inferior to the normal-weight children in fitness items such as standing long jump, pull-ups, sit-ups, step test, and total fitness scores. While no differences in lying trunk extension and standing trunk flexion for body flexibility were observed, the obese children were found to be superior to the normal weight children in static strength such as grip and back strengths. 2. The poor physical fitness of the obese children was found to be negatively affected by their excess body fat, rather than body weight, and that this trend was more pronounced for boys than for girls. 3. The intervention study clearly demonstrated that children in the experimental group improved in physical fitness for most items, especially in abdominal muscle endurance, aerobic capacity, and total physical fitness. 4. It was shown that the diet-exercise program, which comprised guidance on physical exercise and individual nutrition counseling was very useful, because the participants should decrease a considerable in percent overweight and body fat, but without limiting their linear growth velocity or reducing their LBM. PMID- 8453114 TI - [Study on odor control using wood vinegars]. AB - The effectiveness of wood vinegars reducing or eliminating offensive odors, associated with cattle breeding, was studied. The results obtained were as follows: 1. Analyzed were 0.7-7.2% acetic acid and 0.5-1.8% methyl alcohol as main contents. 2. Gaseous odorants, such as ammonia, trimethylamine, n-butyric acid were almost eliminated through absorption using 1-20% wood vinegar solutions. 3. The same gaseous odorants, mentioned above, when confined to an airtight vessel, were eliminated in a short time by adding a little volume of wood vinegars to it. The effect was maintained for 2 weeks. 4. A sensory test was performed to evaluate the degree of deodorization, such as odor intensity and odor acceptability. Results showed that wood vinegars have a good deodorant effect on the offensive odors. PMID- 8453115 TI - [On the "emergency life-saving technician's law"]. PMID- 8453116 TI - [Nationwide survey of smoking prevalence among school students in Japan]. AB - In 1990, a nationwide random survey of smoking habits among junior and senior high school students was conducted in order to study the smoking prevalence among adolescents in Japan. The self-administered anonymous questionnaires on personal smoking status were sent to all students in sample schools. Seventy junior high schools and thirty-three senior high schools responded with 57,566 questionnaires returned, of which 57,189 were subjected to analysis after excluding incomplete and inconsistent questionnaires. The results were as follows; 1) The percentage of experimenters who had smoked even once was 23.3% among boys and 8.7% among girls in the first grade of junior high school (seventh grade). The percentage increased with school grade and reached nearly half of boys and nearly one sixth of the girls in the third grade of senior high school (twelfth grade). 2) The smoking rate was much higher among boys than girls, and the current smoking rate in the first grade of junior high school was 4.0% for boys and 1.5% for girls. Current smoking rate increased with grade, reaching 25.5% for boys and 4.9% for girls in the third grade of senior high school. 3) While the percentage of regular smokers in the first grade of junior high school was less than 1% for both sexes, it went up to 20.3% for boys and 2.6% for girls in the third grade of senior high school. 4) In current smokers, the proportion of boys smoking 1-4 cigarettes per day decreased and that of those smoking 15-19 cigarettes, and 20 or more cigarettes increased with increasing school grade.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8453117 TI - [Illegal sale of tobacco to minors in Japan]. AB - "The Act for Prohibition of Minors from Smoking" which was enacted in 1990 in Japan, states that a parent who tacitly permits smoking by his/her child, and those who sell tobacco to minors knowing that it is for their own use shall be punished. It is, however, unlikely that retailers is ascertaining the age of buyers who appear to be minors and whether the tobacco is for his/her own use. Purchase of tobacco by minors was tested at tobacco retail shops in Tokyo and Omiya city, a suburban city near Tokyo. A 17-year-old senior high school girl in Omiya and a 14-year-old junior high school boy in Tokyo, both dressed in school uniforms, were asked to buy a pack of Mild Seven, one of the most popular brands of domestic cigarettes in Japan. Both students were instructed to tell their age honestly if they were asked, and if asked, they should say that they themselves would smoke it. In Omiya, among 18 shops attempted, the student was refused tobacco, because of being a minor, at only one shop. At one shop, the student was told to buy tobacco from a vending machine. In Tokyo, at 19 out of 20 shops attempted, the student was able to buy tobacco without any problems. At the only shop where he had problems, he was instructed to buy it from the vending machine belonging to the shop. Although prohibition of sale of tobacco to minors is important, it is clear that such prohibition is by no means effective without a strict enforcement system by both the health sector as well as the police. PMID- 8453118 TI - [Smoking cessation rate among attendants and non-attendants to lung cancer screening]. PMID- 8453119 TI - [The results of lung cancer screening under the health and medical services law for the aged (1st report). Equipment and manpower of the X-ray examination system in the Japanese Association of Tuberculosis Prevention]. PMID- 8453120 TI - [Significance of short-term blood pressure variation in health management]. AB - Blood pressure is known to vary under the influence of many factors. Although this variation can also occur in the short term, the significance of short-term blood pressure variation remains to be explained. The purpose of this study was to study the significance of short-term blood pressure variation in health management. Blood pressure was measured on 505 railway employees using an automatic blood pressure recorder based on an oscillometric method. "Continual blood pressure measurement" in which 5 blood pressure measurements were made at one-minute intervals was used. The following conclusions were obtained. 1. Blood pressure gradually fell during the 5 measurements made at one-minute intervals. There was a significant variation between the 1st and 2nd measured blood pressures, but there was no significant variation between the 4th and 5th measured blood pressures in most cases. These results suggest that 4 measurements made at one-minute intervals are needed to obtain stable blood pressure. 2. According to analysis of covariance, both sex and age had an influence on short term blood pressure variation, but the body mass index (BMI) did not. 3. According to cluster analysis using 8 blood pressure variations, all subjects were classified into 4 clusters. These clusters showed significant relationship to age for males and BMI for females. PMID- 8453121 TI - Double-buttress laparoscopic herniorrhaphy. AB - To determine if laparoscopic inguinal herniorrhaphy can be performed safely in unselected patients, the authors' first 100 consecutive laparoscopic inguinal hernia repairs were reviewed. All patients with inguinal hernias who were candidates for general anesthetic were accepted for the study. Their ages ranged from 18 to 84 years. One hundred and six hernias were laparoscopically repaired in 95 males and 4 females. One male patient required an open hernia repair. The first 14 patients were repaired with a preperitoneal patch and plug technique, and the next 85 with the double-buttress transabdominal preperitoneal approach. Two pieces of polypropylene mesh were stapled to the transversalis fascia, ileopubic tract, and Cooper's ligament after the preperitoneal dissection of the hernia was completed. The first piece was placed over the indirect space, with a slit for the cord medially, and the second piece was placed over the entire direct and indirect area. Patients have been followed from 8-18 months. To date, no recurrence has developed. Complications have included seroma, inferior epigastric bleeding, trocar hernia, and neuralgia. Patients have returned to work and normal activity in 2 days to 2 weeks, with an average of 1 week. PMID- 8453122 TI - Laparoscopic cholecystectomy: morbidity and mortality in a community teaching institution. AB - From November 1989 to December 1990, 474 elective laparoscopic cholecystectomies were performed. This study analyzes the first year's experience with regard to complications, postoperative response in terms of pain and nausea, and time back to activity and work. There were 369 females and 105 males in the group. The average age was 51.5 years. Of these, 394 were discharged within 23 h and 80 required admission postoperatively. Of the group requiring hospitalization, there were 10 (2.1%) major complications, 37 (7.8%) minor complications, 14 (3.0%) aborted laparoscopic cholecystectomies, and 19 (4.0%) others. Major complications occurred early in the surgeon's experience, all but two within the surgeons' first 25 cases. Patients in the short stay group were followed-up with a phone questionnaire. In this group, most patients experienced minimal abdominal pain following surgery, with an average score of 2.4 (SD = 1.38) on a scale of 1 (absent) to 5 (extreme). At home, 48.6% of patients experienced some form of postoperative discomfort. Of these, 38.2% experienced abdominal pain, 18.7% shoulder pain, and 32.7% nausea. The average postoperative time to resume normal daily activity was 7.9 days (SD = 8.2) and to return to work was 11.6 days (SD = 9.9). PMID- 8453123 TI - The role of ERCP and therapeutic biliary endoscopy in laparoscopic cholecystectomy. AB - The widespread use of laparoscopic cholecystectomy for the treatment of symptomatic gallstones has been associated with an increased use of diagnostic and therapeutic biliary endoscopy to treat common bile duct stones and postoperative complications. In 250 patients with successful laparoscopic cholecystectomy, 35 were selected for preoperative ERCP evaluation after fitting the criterion of clinical evidence with common bile duct stones (ultrasound and biochemical data). Stones were found in 16 of 35 patients (45.7%). Endoscopic sphincterotomy with stone removal was successfully carried out during the procedure. Laparoscopic cholecystectomy was performed 1 or 2 days after endoscopic sphincterotomy with good result. Only one patient without clinical evidence of common bile duct stones developed postoperative retained stone; he was successfully treated by endoscopic sphincterotomy. Three patients with postoperative bile leakage were successfully treated with endoscopic nasobiliary drainage. Diagnostic and therapeutic ERCP procedures should incorporate the newly developed method of laparoscopic cholecystectomy in order to provide a more safe and minimal invasive therapy. PMID- 8453124 TI - Safety of teaching laparoscopic cholecystectomy to surgical residents. AB - As laparoscopic cholecystectomy evolves into the "standard" method for gallbladder removal, it has become necessary for surgical residents to safely acquired the necessary skills to perform the procedure. To determine the safety of this procedure in the hands of residents, the authors evaluated the first 100 attempted laparoscopic cholecystectomies performed by a resident in the role of "surgeon." Ninety-one of the 100 procedures were successfully completed laparoscopically and 9 required conversion to laparotomy: 5 technically difficult cases, 2 common duct explorations, and 2 for intraoperative complications. At Cooper Hospital in New Jersey, essentially all patients requiring cholecystectomy are first attempted laparoscopically. Seventy-seven patients had chronic cholecystitis and 23 had acute disease. Twenty-two patients had intraoperative cholangiograms and two had laparoscopic common bile duct exploration. For the laparoscopically-completed procedures, average operative time was 91 min and showed a downward trend as each resident gained experience. Three (3%) major complications occurred: one colon laceration, one common bile duct injury, and one postoperative bile collection. For the 91 laparoscopically-completed procedures, 53 patients were discharged on postoperative day 1 and 20 on postoperative day 2. Average postoperative hospitalization was 1.7 days. Overall, these results were comparable to those reported in the literature by attending and private surgeons. The authors conclude that laparoscopic cholecystectomy can be performed safely by supervised residents acting as primary surgeon with outcomes similar to those obtained by trained attending surgeons. PMID- 8453125 TI - Routine or selective intraoperative cholangiography in laparoscopic cholecystectomy. AB - The routine versus selective use of intraoperative cholangiography has been the subject of debate for some time. Most authors currently advocate routine intraoperative cholangiography with laparoscopic cholecystectomy. The authors report their experience with the selective and routine utilization of intraoperative cholangiography at two institutions. At institution A, 155 laparoscopic cholecystectomies were attempted, and 21 cholangiograms were performed (based on preoperative criteria of ultrasound, liver function tests, and history of jaundice, or intraoperative anatomical uncertainty). At institution B, 164 laparoscopic cholecystectomies were attempted and 127 cholangiograms were performed (a routine intraoperative cholangiography policy). At institution A, there were no common bile duct injuries but there was one retained stone. At institution B, there was one common bile duct injury and no retained stones. The patient with the retained stone from institution A had a preoperative indication (total bilirubin = 4.4 mg/dl) for a cholangiogram, but it was not performed due to technical difficulties. This patient later required endoscopic sphincterotomy with stone extraction. One patient at institution B had a choledochotomy which was detected by intraoperative cholangiography (IOC). This was managed with a T-tube. The selective use of cholangiograms in laparoscopic cholecystectomy will not yield a higher incidence of common bile duct injuries or retained stones compared to routine use. Further, a cholangiogram may not necessarily prevent choledochotomy but can prevent extension of common bile duct injury. Thus, it should always be performed when there is anatomic uncertainty. PMID- 8453126 TI - Laparoscopic cholecystectomy in pregnancy. AB - Pregnancy has generally been considered a contraindication to laparoscopic cholecystectomy. The authors present a case of laparoscopic cholecystectomy in a 37-year-old patient who was 18 weeks pregnant. Laparoscopic cholecystectomy can be safely accomplished during pregnancy, provided that the open technique of insertion of the first cannula is used, and all subsequent trocars be inserted under direct vision. PMID- 8453127 TI - Laparoscopic repair of ruptured duodenal peptic ulcer: a case report. AB - Ruptured duodenal peptic ulcer is a serious complication of ulcer disease that occurs in approximately 5% of cases and accounts for over 70% of deaths associated with peptic ulcer disease. This case report details the management of a 67-year-old male with a ruptured duodenal peptic ulcer who presented to the emergency room with acute onset of severe abdominal pain. There was no past history of ulcer disease. An abdominal x-ray suggested the presence of free air, and diagnostic laparoscopy was performed. The superior exposure afforded by this minimally invasive technique not only permitted an exact diagnosis to be made, but also afforded a means to expeditiously correct the pathologic defect. PMID- 8453128 TI - Laparoscopic-directed small bowel resection for jejunal diverticulitis with perforation. AB - The authors report a case in which an 87-year-old woman underwent diagnostic laparoscopy for abdominal pain of unknown etiology. Jejunal diverticulosis was discovered with diverticulitis and perforation into the mesentery. Visualization of the appendix, ovaries, uterus, colon, and liver ruled out additional pathology. The disease was serious enough that resection of the involved jejunum was necessary. With the aid of the laparoscope, the incision was directed nearer to the area of the disease. A 5 cm left upper quadrant transverse incision was made, allowing removal of perforation and the diseased bowel. Primary resection and anastomosis were performed. This case sets a precedence for use of exploratory diagnostic laparoscopy and particularly small bowel resection for symptomatic diverticulitis. The authors believe that this technique results in less postoperative pain, allowing for a prompt recovery with minimal morbidity and mortality, particularly in the elderly population. PMID- 8453129 TI - Laparoscopic orchiectomy in a patient with complete androgen insensitivity. AB - Many procedures that were once approached exclusively through large abdominal incisions are now accomplished using operative laparoscopic techniques with shorter, less expensive hospital stays and significantly reduced convalescence. This report describes a laparoscopic orchiectomy in a patient with complete androgen insensitivity and discusses the indications for gonadectomy in phenotypic females with an XY karyotype. PMID- 8453130 TI - Laparoscopic rectopexy. AB - A 74-year-old female suffering from recurrent rectal prolapse underwent laparoscopic rectopexy. A modified sling rectopexy was performed with excellent results. The authors believe that this is the first report of this technique. PMID- 8453131 TI - Subcutaneous wire traction technique without CO2 insufflation for laparoscopic cholecystectomy. AB - One hundred laparoscopic cholecystectomies were performed since April 1991. Eleven patients were treated with a new technique without CO2 insufflation, using a traction device to elevate the right upper quadrant wall. Two Kirschner wires were introduced subcutaneously to permit the abdominal wall to be lifted for satisfactory laparoscopic view, as the gas insufflation technique yields. Preoperative evacuation of the intestines and intraoperative muscle relaxation are necessary for easy and successful cholecystectomy. Three cases were converted to laparotomy because of remarkably distended intestine due to incorrect endotracheal intubations. No complications related to subcutaneous wire traction technique were noted in this series. Subcutaneous wire traction technique provides a simpler, and possibly safer alternative to the gas insufflation technique. PMID- 8453132 TI - Laparoscopic and hysteroscopic approach for tubal anastomosis. AB - The laparotomy approach for microsurgical repair of tubo-tubal anastomosis is a well-established method. This article describes a novel technique of end to end tubo-tubal re-anastomosis using the minimally invasive methods of video laparoscopy, video hysteroscopy, and lasers in four women. This procedure is applicable to women of reproductive age who have previously been subjected to voluntary sterilization procedures. The long-term results of this new technique remain to be evaluated. However, the minimal surgical approach has met with early success and patient approval. PMID- 8453133 TI - An easy approach to laparoscopic cholangiography. AB - Laparoscopic cholecystectomy has become the procedure of choice for surgical removal of the gallbladder. Intraoperative cholangiography is often needed to define ductal anatomy and to detect choledocholithiasis, a procedure which often proves more difficult than its open counterpart. Several newer cholangiocatheters have been introduced which have made laparoscopic cholangiography easier, however, the standard approach through an existing operating port will usually place the catheter at an odd angle, making catheterization of the cystic duct all but impossible in some cases. To avoid this acute angle between the catheter and the cystic duct, the authors have begun using a standard central line introducer as the port through which the catheter is inserted. When placed in the proper position through the lateral abdominal wall, this approach allows the catheter to be inserted parallel and in line with the cystic duct for much easier and faster cannulation. PMID- 8453134 TI - Ligation of the renal pedicle during laparoscopic nephrectomy: a comparison of staples, clips, and sutures. AB - Evaluation of the role of staples, clips, and sutures for laparoscopic ligation of the renal artery revealed that occluding the renal artery with three, 9 mm titanium clips is as secure as occluding the renal artery with standard 2-0 and 0 silk ligatures. However, a triple staggered line of 2.5 mm staples placed across the renal artery was not as secure as either clips or silk sutures. The authors also studied eight female farm pigs who underwent laparoscopic nephroureterectomy with en masse stapled occlusion of the renal hilum. In one animal, an arteriovenous fistula was documented 6 months postoperatively. Currently, when laparoscopically occluding the renal hilum, the authors recommend a thorough dissection of the renal artery and renal vein; each should then be separately occluded so that three individually placed titanium clips remain on the stump of the renal artery and on the renal vein. PMID- 8453135 TI - A lost pledget during laparoscopic cholecystectomy. PMID- 8453136 TI - Percutaneous decompression of the gallbladder. PMID- 8453137 TI - National Institutes of Health Consensus Development Conference Statement: Gallstones and Laparoscopic Cholecystectomy. September 14-16, 1992. PMID- 8453138 TI - SAPHO: the impossible acronym. PMID- 8453139 TI - Papuloerythroderma: disease or pattern? PMID- 8453140 TI - Cutaneous reactions to analgesic-antipyretics and nonsteroidal anti-inflammatory drugs. Analysis of reports to the spontaneous reporting system of the Gruppo Italiano Studi Epidemiologici in Dermatologia. AB - We analyzed the cutaneous reactions to systemic analgesic-antipyretics and non steroidal anti-inflammatory drugs reported to the spontaneous reporting system of the Gruppo Italiano Studi Epidemiologici in Dermatologia (GISED). The system has been active since 1988, with periodic intensive surveillance exercises, and 202 dermatologists have collaborated. Up to December 1991, 2,137 reactions had been collected, of which 713 were reactions to systemic analgesic-antipyretics and nonsteroidal anti-inflammatory drugs. A general profile of the reactions was identifiable. It included, in order of frequency, urticaria/angioedema, fixed eruptions, exanthemas, erythema multiforme and Stevens Johnson syndrome. Fixed eruptions and Stevens Johnson syndrome were reported with exceedingly high frequency in association with feprazone. Our system also revealed previously unreported reactions, including fixed eruption to nimesulide, fixed eruption to piroxicam and fixed eruption to flurbiprofen. PMID- 8453141 TI - Altered muscle metabolism in pustular psoriasis (Zumbusch type): demonstration by 31P magnetic resonance spectroscopy. AB - We report a patient with pustular psoriasis (Zumbusch type) with diffuse muscle pain. Evaluation of skeletal muscle metabolism during rest, graded levels of exercise and recovery was performed using 31phosphor magnetic resonance spectroscopy (31P MRS). Our results underline the systemic character of severe pustular psoriasis. The clinical improvement after drug therapy (prednisolone and etretinate) correlated well with the measurable changes in vivo of several metabolites and indices important in muscle contraction, such as phosphocreatine (PCr), inorganic phosphate (P(i)), intramuscular pH and the phosphorylation potential (PCr/Pi). Abnormal accumulation of sugar phosphates (phosphomonoester) as well as their slow resolution during recovery reflect profound alteration of metabolism in the sense of block in glycolysis. Our results show that 31P MRS is well suited to identify and measure subtle changes in the muscle metabolism occurring in pustular psoriasis. PMID- 8453142 TI - SAPHO syndrome. AB - Four women with pustulosis palmoplantaris (PPP) and associated sternocostoclavicular hyperostosis are described. The connection between the two diseases is not coincidental: it is encountered in 9.4% of PPP patients, and was reported in the French literature as part of the SAPHO (synovitis acne pustulosis hyperostosis osteomyelitis) syndrome. This syndrome is linked to the spondyloarthropathies, having an increased prevalence of HLA B27 and occurrence of sacroiliitis. None of our patients had HLA B27, but HLA A26 was found in the 3 patients examined. No conclusion can be drawn from this finding, however, since this antigen is found in 21.7% of Ashkenazi Jews. Recognition of this syndrome by dermatologists will improve diagnosis and treatment. PMID- 8453143 TI - Bimodality in age of onset of psoriasis, in both patients and their relatives. AB - The ages at onset of 245 female and 211 male psoriasis (Ps) patients were recorded. The distribution of age of onset in both sexes is bimodal, with separation at the age of 40 years into an early-onset group and a late-onset group. These distributions were normal (Gaussian) with equal variances. These data are compatible with the hypothesis that there are two genotypes for Ps. Further evidence for this hypothesis is provided by the relationship between age of onset and number of affected relatives. The latter, corrected for age at time of study, demonstrates a mixture of two negative binomial distributions, also with likely separation at the age of 40 years. The age distribution of Ps patients reflects the bimodality of age of onset, but with larger means and variances. PMID- 8453144 TI - Ofuji papuloerythroderma: report of a European case. AB - The trunk and the limbs of an 82-year-old man were covered with large sheets of flat-topped erythematous papules arranged in a reticulate pattern which suddenly coalesced assuming erythroderma-like aspects. Body and positional folds were characteristically spared (deck chair sign). Mild eosinophilia was present. The histological and immunohistochemical examinations revealed an unspecific eczematous pattern. After systemic steroids and PUVA treatment the patient recovered from the dermatosis. Papuloerythroderma is a distinctive clinical entity, but it is not clear whether the dermatosis is the skin marker of systemic pathological conditions or a precursor of cutaneous lymphomas. PMID- 8453145 TI - Ofuji papuloerythroderma: a new European case. AB - We report a new case of Ofuji papuloerythroderma. There was no obvious sign of lymphoma or underlying malignancy. This is the 7th European case of papuloerythroderma. This recently described clinical entity is characterized by a pruritic eruption of widespread red-brown flat papules sparing the skin folds, with eosinophilia. The recognition, report and follow-up of further cases are necessary to clarify its relationship with paraneoplastic syndromes, hypereosinophilic syndrome, or prelymphoma skin eruptions. PMID- 8453146 TI - Papuloerythroderma: report of a European case. AB - A case of papuloerythroderma in a 74-year-old woman is presented. She had blood eosinophilia (up to 4,130 mm3), elevated serum IgE (2,369 IU/ml) and responded to oral steroids. PMID- 8453147 TI - A new case of isolated trichothiodystrophy. AB - We describe a new case of isolated trichothiodystrophy. This entity is characterized by sparse and brittle hair, low sulfur hair content, tiger tail pattern of the hair under polarizing microscopy, clean transverse fractures through the hair shaft and absent or defective hair cuticles. To our knowledge there are only two reported cases of isolated trichothiodystrophy without associated additional ectodermal or neuroectodermal dysplasias. Polarized microscopy of cut hair showed transverse fracture points (trichoschisis) and alternating dark and bright bands. Low sulfur content of the hairs was confirmed by amino acid analysis. Many acronyms and eponyms have been created to describe sulfur-deficient brittle hair associated with neuroectodermal abnormalities, leading to confusion. We suggest to use a simple classification scheme, according to increasing severity of associated features as proposed by Van Neste. PMID- 8453148 TI - A case of epidermolysis bullosa hereditaria--dominant dystrophic type of Cockayne and Touraine. AB - We report a patient with the Cockayne and Touraine type epidermolysis bullosa dystrophica domains. A 6-year-old Japanese female developed blisters and erosions on the extremities 3 months after birth. Immunohistology showed a linear binding pattern of the monoclonal antibody against type VII collagen (LH:2) on the epidermal basement membrane. By means of electron microscopy and morphometric analysis, it became apparent that the anchoring fibrils were rudimentary in structure and reduced in number. PMID- 8453149 TI - Cutaneous ossification in Albright's hereditary osteodystrophy. AB - A 23-year-old woman presented with subcutaneous ossification, which together with short stature, stocky physique, round face and brachydactyly suggested Albright's hereditary osteodystrophy (AHO). Serum calcium and phosphorus levels were normal. AHO refers to the phenotype of the syndromes of pseudo-hypoparathyroidism (PHP) type Ia and pseudopseudohypoparathyroidism (PPHP), both considered genetically related variants with a defect of the alpha subunit of the stimulatory G protein of adenylate cyclase, necessary for the action of parathyroid and other hormones using cyclic AMP as an intracellular second messenger. PPHP differs from PHP in that it lacks parathyroid hormone resistance manifesting itself as hypocalcemia. Other endocrine end organ unresponsiveness, e.g. hypothyroidism and hypogonadism, may also be found with PHP. Both PHP and PPHP usually exhibit characteristic phenotypic abnormalities, of which subcutaneous ossification may be a presenting feature. The differential diagnosis of cutaneous calcification and ossification is outlined. PMID- 8453150 TI - Eosinophilic pustular folliculitis (Ofuji's disease) with response to indomethacin. PMID- 8453151 TI - Pustular vasculitis with clinical feature of pustular psoriasis and sternoclavicular hyperostosis. AB - We report the case of a 51-year-old Japanese man with a unique pustulosis. He had multiple erythematous plaques and numerous pinpoint pustules on the trunk and extremities resembling pustular psoriasis. Histologic features revealed a fully developed intraepidermal abscess filled with neutrophils and disrupted epidermal keratinocytes. Mild leukocytosclastic vasculitis was seen in the underlying dermis. A direct immunofluorescence study revealed IgM, Clq, C3 and fibrinogen deposits in the dermal vessels. The patient had also sternoclavicular hyperostosis. We think that this represents a unique type of pustular vasculitis distinct from pustular psoriasis. PMID- 8453152 TI - Carcinoma cuniculatum of the nail apparatus: report of three cases. AB - Three patients affected by carcinoma cuniculatum involving the nail apparatus are reported. The toes were affected in 2 cases, the thumb in 1 case. In the first patient the tumour developed in the subungual area and resulted in loss of the toe-nail. In the second patient the tumour originated on the dorsum of the toe and subsequently involved the proximal nail fold. In the third patient the tumour developed in the nail bed resulting in loss of the lateral part of the nail plate. The pathology showed in all cases invaginating strands of well differentiated keratinocytes, some of which had central crypts containing keratinous debris. Radical excision of the tumour required disarticulation of the digit in 2 cases, whereas Mohs micrographic surgery was performed in the third case. PMID- 8453153 TI - Urticaria-pigmentosa-like lesions in acute lymphoblastic leukaemia (2 cases). AB - Two males aged 12 and 38 years presented with widespread severely pruritic blackish spots for 15 days. Widespread slate-grey patches and erythematous hyperpigmented plaques were observed with a positive Darier's sign. There were associated neck swellings, abdominal pain, anorexia, weight loss and bleeding gums in both. Peripheral blood and bone marrow showed blast cells, anaemia and thrombocytopenia. Cell surface markers confirmed the presence of acute lymphoblastic leukaemia. Skin biopsy showed an infiltrate of lymphoblasts as well as mast cells. Partial response was noted with cytotoxic therapy in 1 patient. Thus lesions mimicking urticaria pigmentosa may be the presenting sign of acute lymphoblastic leukaemia. PMID- 8453154 TI - Autoantibodies to nuclear mitotic apparatus in a patient with vitiligo and autoimmune thyroiditis. AB - Circulating autoantibodies against the nuclear mitotic apparatus (NuMA) protein have been detected in sera of patients with a variety of connective tissue diseases. A close relation of anti-NuMA antibodies to define subsets of these diseases could not be established. This is the first description of a patient with vitiligo, autoimmune thyroiditis and a high titer of antibodies against NuMA on Hep-2 cells. The possibility of a beginning of multiple autoimmune syndrome cannot be excluded. PMID- 8453155 TI - Fusarium solani cutaneous infection in a neutropenic patient. AB - A 47-year-old woman with acute myeloblastic leukemia developed disseminated papules and pustules after chemotherapy. A skin biopsy specimen revealed fungal vasculitis and grew Fusarium solani. The patient died despite treatment with amphotericin B. The isolate was resistant to amphotericin B, imidazole and 5 fluocytosine. Fusarium should be recognized as a potential cause of deep fungal infection in immunocompromised patients. PMID- 8453156 TI - Systemic sclerosis and exposure to trichloroethylene. PMID- 8453157 TI - White fibrous papulosis of the neck. PMID- 8453158 TI - Significance of polythelia. PMID- 8453159 TI - Sorbitol content of selected oral liquids. AB - OBJECTIVE: Excipients in pharmaceuticals usually are considered inert, and may be overlooked in the differential diagnosis of diarrhea. Sorbitol-containing medicinal liquids are capable of inducing osmotic diarrhea. We reviewed the oral liquids in our formulary to determine their sorbitol content and to evaluate the availability of this information. DESIGN: The oral liquids stocked by our hospital were determined through a computer search and manual inspection of the pharmacy storeroom. Three common sources of drug information were consulted to determine each product's sorbitol content: manufacturers' product information, American Hospital Formulary Service (AHFS) Drug Information 91, and Facts and Comparisons Drug Information. We then contacted each manufacturer by mail or telephone to verify the information. SETTING: The study was conducted at the University of Cincinnati Hospital, a tertiary-care, teaching hospital. RESULTS: A total of 129 products (98 chemical entities) were reviewed. Fifty-four (42 percent) of the products examined contained sorbitol. The frequency of sorbitol presence by liquid type was: solutions (33 percent), suspensions (43 percent), syrups (59 percent), elixirs (43 percent), concentrates (67 percent), drops (33 percent), tinctures (0 percent), and emulsions (0 percent). The percentage of listings indicating the presence of sorbitol was: manufacturer's product information (79 percent), Facts and Comparisons (52 percent), and AHFS Drug Information 91 (13 percent). Only three of the 54 products had the exact sorbitol content stated in any source. PMID- 8453160 TI - Contamination study of multiple-dose vials. AB - OBJECTIVE: To document the number of opened, dated, and expired multiple-dose vials (MDVs) in patient-care areas and to determine what proportion of MDVs were contaminated with bacteria or cellular debris. DESIGN: Every tenth opened MDV (69/656) identified on the wards was collected, ensuring representation from each nursing unit. Contents were examined for contamination. SETTING: Medical-school affiliated, tertiary care center. MAIN OUTCOME MEASURES: (1) Visual inspection for debris, medication type, location, lot number, manufacturer's expiration date, and date of opening; (2) culture in solid and broth media for bacterial growth; and (3) staining and microscopic examination for cellular constituents. RESULTS: No vials had been dated after opening and 4.6 percent were expired according to the manufacturer's expiration date. No bacterial contamination was evident; however, one vial was contaminated with red blood cells. CONCLUSIONS: Transmission of infection via contaminated MDVs has been well documented and contamination with red blood cells raises concerns about potential for transmission of bloodborne pathogens. Recommendations include dating MDVs after opening, emphasizing the need for proper aseptic technique, and discarding MDVs on the manufacture's date of expiration. PMID- 8453161 TI - Use of DRUGLINE--a question-and-answer database. AB - BACKGROUND: DRUGLINE is a full-text, question-and-answer database offering drug information that has been evaluated as a result of consultations in a drug information center. A problem-oriented database such as DRUGLINE can be an efficient way to meet the increasing need among healthcare professionals for timely and accurate drug information. OBJECTIVE: To investigate how DRUGLINE was used during the years 1988 and 1990 and to identify any changes in needs, expectations, satisfaction, and use that occurred during those two years. DESIGN: This study investigated the use of DRUGLINE during two separate years. Questionnaires relating to DRUGLINE use during 1988 and 1990 were sent on two occasions to all users having access to the database. The anonymous questionnaires contained 17 and 18 questions, respectively. SETTING: The setting included MEDLINE/DRUGLINE use in healthcare institutions, pharmacies, medical libraries, and the pharmaceutical industry. PARTICIPANTS: The questionnaires were sent to all customers of the database host Medical Information Centre at the Karolinska Institute Library and Information Centre having access to DRUGLINE during 1988 and 1990. PMID- 8453162 TI - Insect repellent (N,N-diethyl-m-toluamide) cardiovascular toxicity in an adult. AB - OBJECTIVE: To describe a case of N,N-diethyl-m-toluamide (DEET)-induced cardiovascular toxicity in an adult and reviews other cases that have been reported in the published literature. Human and animal data available on DEET pharmacokinetics are reviewed and factors that predispose an individual to DEET toxicity are identified. DATA SOURCES: Case report information was obtained through personal contact with the patient during hospitalization and by telephone, and also from the patient's medical records. Computerized literature searches were conducted with the following systems to obtain medical literature on DEET toxicity: TOXLINE, International Pharmaceutical Abstracts, and MEDLINE. Index Medicus was searched manually. STUDY SELECTION: All reported cases of DEET toxicity in children and adults were reviewed. DATA EXTRACTION: Case reports were evaluated for the quantity of the DEET exposure (topical or oral), the clinical manifestations of the exposure, and the outcome of the exposure. DATA SYNTHESIS: This case is similar in some aspects to those already in the literature; however, very few cases of DEET toxicity in adults have been reported. Cardiovascular toxicity in humans related to DEET application has not been previously reported in the published medical literature. DEET exposure (topical or oral) results in a highly variable clinical course. Whether the outcome is death or recovery without sequelae is difficult to predict. CONCLUSIONS: Adults, as well as children, are at risk for toxicity from insect repellents. The use of highly concentrated DEET containing insect repellents should be avoided to reduce the risk of toxicity in both children and adults. The consequences of DEET toxicity are variable and unpredictable. PMID- 8453163 TI - Ceftriaxone distribution and protein binding between maternal blood and milk postpartum. AB - OBJECTIVE: To study postpartum distribution and protein binding of ceftriaxone (CTX) between maternal blood and milk and to discuss risk factors and possible impact for the neonate. DATA SOURCES: Reference articles and books are identified in the text. DATA SYNTHESIS: CTX distribution and protein binding between maternal blood and milk postpartum were studied in a patient at term presenting with acute pyelonephritis caused by Escherichia coli. The antibiotic therapy prescribed pending bacteriology results consisted of CTX 2 g/d, ornidazole 1 g/d, and tobramycin 3 mg/kg/d. Pharmacokinetics of total CTX were studied after the first 2-g infusion. At plateau (i.e., two days after delivery; seventh infusion), pharmacokinetics and milk distribution of total and free CTX also were studied. No accumulation of CTX was noted in the plasma at plateau. When high dosages of CTX are used (approximately 2 g), its penetration into the milk is important (i.e., protein binding capacity is overwhelmed). No notable adverse reactions occurred in mother or child. Thus, an important diffusion into the milk (4.4 percent of the dose) appears not to be clinically important. Our knowledge of both metabolism and milk distribution of drugs with high protein binding (> or = 95 percent) and an acid characteristic should be expanded to better understand their use during both the pregnancy and postpartum periods. Finally, the child of the patient described here has normal initial growth and development at the present time. CONCLUSIONS: Caution should be taken when drugs such as CTX, which have both high protein binding (> or = 95 percent) and an acid characteristic are administered to breastfeeding women. Drugs of this type should be systematically investigated to better understand their use during pregnancy and postpartum. PMID- 8453164 TI - Diazepam by continuous intravenous infusion for status epilepticus in anticonvulsant hypersensitivity syndrome. AB - OBJECTIVE: To report a case of status epilepticus in a patient with anticonvulsant hypersensitivity syndrome (AHS) that was controlled successfully using continuous intravenous infusion diazepam. AHS and alternatives for treatment of status epilepticus are also reviewed. DESIGN: Single case report. SETTING: 217-bed children's university hospital. PATIENT: Four-year-old, 20-kg girl, diagnosed with idiopathic tonic-clonic epilepsy, who developed AHS to phenobarbital and phenytoin and status epilepticus unresponsive to lorazepam. RESULTS: Diazepam intravenous infusion at dosages titrated to 8 mg/h was used successfully to control seizures for eight days until signs and symptoms of AHS had resolved and maintenance therapy with valproic acid was started. CONCLUSIONS: Continuous intravenous infusion diazepam is a reasonable therapeutic choice for the management of status epilepticus in a patient with AHS when traditional therapy such as phenytoin and phenobarbital cannot be used. PMID- 8453165 TI - Arthropathy secondary to ciprofloxacin in an adult cystic fibrosis patient. AB - OBJECTIVE: To report a case of possible ciprofloxacin-induced arthropathy in an adult patient with cystic fibrosis (CF). CASE SUMMARY: A 25-year-old man with CF received three separate courses of ciprofloxacin therapy at usual doses for acute pulmonary exacerbations of his disease. During the second and third courses, the patient experienced bilateral swelling of his knees between two to three weeks after initiation of each course. Both times symptoms markedly decreased after discontinuation of the drug. The patient had no prior history of arthropathy. Furthermore, during the last two acute exacerbations of his CF, he did not receive ciprofloxacin and did not experience any symptoms of arthropathy. DISCUSSION: Prior cases of quinolone-induced arthropathy involving pediatric CF patients or adult patients without CF have been reported in the literature. We report the first case of such an arthropathy in an adult patient with CF. The findings are supported by a rechallenge with the drug. CONCLUSIONS: It is likely that ciprofloxacin may produce arthropathy in adult as well as pediatric patients with CF. Quinolones should be considered as a possible cause of arthropathy in adult CF patients. PMID- 8453166 TI - Hypoglycemia secondary to trimethoprim/sulfamethoxazole administration in a renal transplant patient. AB - OBJECTIVE: To report a case of trimethoprim/sulfamethoxazole (TMP/SMX)-induced hypoglycemia in an immunosuppressed renal transplant patient. DATA SOURCE: English-language journal articles and reference texts identified via a MEDLINE search and a bibliographic review of pertinent data sources. DATA SYNTHESIS: Hypoglycemia resulting from the combination of sulfonylureas and sulfonamides is a recognized drug interaction. Hypoglycemia induced by sulfonamides alone may be encountered less frequently. Previously reported cases of TMP/SMX-induced hypoglycemia postulated that the sulfonamide mimics hypoglycemic sulfonylurea agents and stimulates pancreatic islet cells to secrete insulin. We report a case of hypoglycemia following the administration of high-dose TMP/SMX in a renal transplant patient. Elevated C-peptide concentrations following the hypoglycemic episode indicate that hypoglycemia resulted from increased endogenous insulin secretion. CONCLUSIONS: Hypoglycemia has been a rarely encountered result of TMP/SMX use. Patients receiving TMP/SMX, particularly those with impaired renal function and those receiving high doses, should be monitored closely for hypoglycemia. PMID- 8453167 TI - Pain management with intravenous ketorolac. AB - OBJECTIVE: To report a case in which intravenous ketorolac was used successfully on a chronic basis to treat cancer pain. DATA SOURCES: Clinical and compatibility studies obtained through a computer literature search. STUDY SELECTION: We identified five reports that specifically addressed intravenous dosing of ketorolac. DATA SYNTHESIS: A 41-year-old man received pain relief from intravenous injections of ketorolac for 11 months. As far as we know, there are no other reports in the literature in which intravenous ketorolac has been used on a chronic basis. CONCLUSIONS: Experience at our institution indicates that intravenous ketorolac is a useful, well-tolerated nonsteroidal antiinflammatory drug that should be investigated further for use in selected pain models. PMID- 8453168 TI - Ciprofloxacin-resistant Haemophilus influenzae infection in a patient with chronic lung disease. AB - OBJECTIVE: To report a case of ciprofloxacin-resistant Haemophilus influenzae infection in a patient with chronic lung disease who was exposed to multiple courses of antimicrobial therapy. CASE SUMMARY: The patient suffered recurrent pulmonary infections and developed bronchiectasis as a consequence of longstanding, severe, combined immunodeficiency disease. He had received ciprofloxacin on several occasions for treatment and prophylaxis of recurrent pulmonary infections. On a recent admission his usual H. influenzae isolate, which had been highly susceptible to ciprofloxacin (minimum inhibitory concentration [MIC] < or = 0.06 mg/L) on previous admissions, was resistant to ciprofloxacin and ofloxacin (MIC 8 and 16 mg/L, respectively). The patient responded to treatment with ceftizoxime and was discharged with oral cefixime, which was to be taken for a total of two weeks. DISCUSSION: Rare isolates of H. influenzae resistant to ofloxacin and lomefloxacin have been noted in Europe and Asia; however, none resistant to the fluoroquinolones have been previously reported in the US, and no resistance has been reported to ciprofloxacin. We believe that repetitive, cycling exposure to ciprofloxacin may have induced the resistance that developed in this patient's flora. CONCLUSIONS: Fluoroquinolones may be added to the list of drugs to which H. influenzae have become resistant. Only judicious use of these drugs will preserve their activity against important pathogens in community-acquired infections. PMID- 8453169 TI - Vitamin E in tardive dyskinesia. PMID- 8453170 TI - Clonidine in pain management. PMID- 8453171 TI - Pharmacotherapy of sexual offenders. AB - OBJECTIVE: To review the definition, sociology, pathogenesis, diagnosis, medicolegal aspects, and pharmacologic treatment of sexual offenders, with emphasis on the antiandrogens, the luteinizing hormone-releasing hormone (LHRH) antagonists, and the serotonergics. DATA SOURCES: An English-language literature search using MEDLINE (1966-1991) yielded clinical trials, case reports, editorials, and review articles. STUDY SELECTION: Emphasis was placed on comparative trials and case reports discussing pedophilia, rape, and exhibitionism. DATA EXTRACTION: Data from controlled human studies were evaluated. The trials were assessed for sample size, duration of therapy, therapeutic response, and incidence of recidivism. CONCLUSIONS: The pharmacologic management of sexual offenders is controversial, and treatment is presently focused on psychotherapy and the use of antiandrogenic medications. Few well controlled, blinded, efficacy trials with adequate sample sizes have been conducted. The populations studied are heterogeneous, and the subjects enrolled present with different sexually coercive behaviors. Consequently, the results of these studies are difficult to extrapolate to the treatment of other sexual offenders. No convincing evidence exists that pharmacologic treatment decreases the recidivism rate. Case reports describing the use of serotonergic drugs and LHRH antagonists hopefully will promote controlled clinical trials. A social consensus must be reached concerning the ethics of using these agents as a part of the treatment of sexual offenders. PMID- 8453172 TI - Loracarbef: a new orally administered carbacephem antibiotic. AB - OBJECTIVE: To discuss the in vitro activity, pharmacokinetics, clinical efficacy, adverse effects, and relative merits of loracarbef, a new orally administered carbacephem antibiotic. DATA SOURCES: Pertinent literature was identified by a review of selected journals and a MEDLINE search. Additional information was provided by the manufacturer of loracarbef. STUDY SELECTION: All studies that have evaluated the clinical efficacy of loracarbef were included. In vitro studies were included if they used similar methodologies. Additional information was incorporated regarding the chemistry, pharmacokinetics, and adverse effects of loracarbef. DATA SYNTHESIS: Loracarbef has antibacterial activity against most community-acquired respiratory tract, skin and skin structure, and urinary tract pathogens. The drug is well absorbed after oral administration and plasma concentrations achieved in patients are greater than the in vitro minimum inhibitory concentrations for most of the above bacteria. Although the majority of the clinical studies with loracarbef have methodologic deficiencies, loracarbef therapy has demonstrated similar efficacy in the treatment of upper respiratory tract (except otitis media), lower respiratory tract, skin and skin structure, and urinary tract infections compared with accepted antibiotics. Potential advantages of the new carbacephem may be improved patient compliance with its less frequent dosing schedule (once or twice a day, depending on the infection), and a low incidence of adverse effects. CONCLUSIONS: Preliminary data indicate that loracarbef may be an alternative agent for the treatment of a variety of community-acquired infections. Additional clinical experience and rigorously controlled comparative clinical trials are necessary to enable practitioners to fully define the therapeutic role of loracarbef. PMID- 8453173 TI - Capsaicin: identification, nomenclature, and pharmacotherapy. AB - OBJECTIVE: To provide a brief overview of the chemical history, analysis, nomenclature, biology, pharmacology, and pharmacotherapy of capsaicin. DATA SOURCES: Chemical Abstracts, Biological Abstracts, and a MEDLINE search were used to identify pertinent literature; selected literature was used in this review. DATA EXTRACTION: Original articles, reviews, and abstracts of articles were used to select material pertinent to the objectives of the review. The volume of material available prohibits comprehensive data extraction. CONCLUSIONS: A history of the use of Capsicum spp. and the predominant active ingredient, capsaicin, the parent compound of a group of vanillyl fatty acid amides, is presented. Distinct structural differences are noted between this compound and the capsaicinoids, especially the synthetic analog nonivamide, which has appeared as an adulterant in capsaicin-labeled products. Analysis shows that although some of these synthetic analogs eventually may prove to be true natural products, conclusive evidence based on isolation and structure elucidation is still absent after decades of attempted isolation from several potential natural sources. Although the crude, dark oleoresin extract of capsicum contains over 100 distinct volatile compounds and therefore may function in many ways dissimilar to capsaicin, the oleoresin continues to be marketed in products with a high degree of variability in efficacy. Capsaicin as a pure white crystalline material, however, acts specifically by depleting stores of substance P from sensory neurons, and has been successful in the treatment of several painful conditions (e.g., rheumatoid arthritis, osteoarthritis, peripheral neuropathies. PMID- 8453174 TI - Allopurinol hypersensitivity syndrome: a review. AB - OBJECTIVE: To review the pathophysiology, pathology, and clinical findings of allopurinol hypersensitivity syndrome (AHS), an infrequent but life-threatening adverse effect of allopurinol therapy. DATA SOURCES: A MEDLINE search (key terms hepatitis, interstitial nephritis, severe hypersensitivity, severe toxicity, vasculitis, toxic epidermal necrolysis, Lyell's syndrome, erythema multiforme, and Stevens-Johnson syndrome) was used to identify cases reported in the literature through the end of 1990. STUDY SELECTION: All cases evaluated met Singer and Wallace's diagnostic criteria for AHS. DATA EXTRACTION: We extracted data from 101 cases of AHS reported in the literature. The following information, when available, was analyzed: (1) patient data (age, gender, medical history), (2) treatment data (daily dosage of allopurinol, duration of treatment, indications, concomitant medications, and (3) adverse-event data. DATA SYNTHESIS: Patients were mostly middle-aged men with hypertension and/or renal failure receiving excessive doses of allopurinol primarily for asymptomatic hyperuricemia. Cutaneous rash and fever were the most common clinical findings. CONCLUSIONS: Although the pathophysiologic pathway leading to the development of AHS is unknown, it probably involves an immunologic mechanism following allopurinol accumulation in patients with poor renal function. Our findings suggest that the accepted diagnostic criteria for AHS may be too broad, and we recommend the application of more restrictive criteria. There is no effective treatment for AHS. The use of allopurinol only for accepted indications and in dosages adjusted for a patient's renal function may be the only means of minimizing the incidence of AHS. PMID- 8453175 TI - Selection of activated charcoal products for the treatment of poisonings. AB - OBJECTIVE: To determine if differences exist among currently available activated charcoal products, and if an evaluation of risk versus benefit provides a guide to product selection. DESIGN: National survey by mail. PARTICIPANTS: US manufacturers of activated charcoal products. RESULTS: Six companies market activated charcoal products in ready-to-use containers. The products differ in surface area of charcoal, sorbitol content, and packaging (aqueous or powdered form). No significant differences were noted in the cost of 25- to 30-g units or efficacy based on surface area of activated charcoal. The addition of sorbitol to activated charcoal, particularly at high concentrations, increases the incidence of adverse effects, especially in children. CONCLUSIONS: Although differences do exist among currently marketed activated charcoal products, the clinical significance of these variations is unknown. Based on an evaluation of risks and benefits, any activated charcoal product that does not contain sorbitol appears to be a suitable choice for treating poisoning victims. PMID- 8453176 TI - Intravenous ciprofloxacin: a position statement by the Society of Infectious Diseases Pharmacists. AB - Intravenous ciprofloxacin is approved for the treatment of urinary tract, bone and joint, skin and soft tissue, and lower respiratory tract infections. Few large, randomized studies comparing its effectiveness with that of other available agents exist; most of these have been published in non-peer-reviewed journal supplements. Intravenous ciprofloxacin is nearly ten times more expensive than the "equivalent" oral dose. Based on the limitations of currently available clinical data, iv ciprofloxacin does not appear to be superior, and is at best comparable in efficacy to other currently available antibiotics. Bacterial resistance, especially in serious infections secondary to P. aeruginosa and S. aureus, is becoming more prevalent. Intravenous ciprofloxacin should be considered an alternative for the treatment of infections of the urinary and lower respiratory tracts only when the following conditions exist: (1) documented bacterial resistance to less-costly regimens with proven efficacy for these indications (e.g., beta-lactams, aminoglycosides, trimethoprim/sulfamethoxazole) and known susceptibility to ciprofloxacin, (2) documented hypersensitivity to first-line agents, or (3) inability to ingest or absorb oral ciprofloxacin. Further clinical trials using higher doses are required before iv ciprofloxacin can be recommended routinely for treatment of serious systemic infections. Because of its poor activity against streptococci, marginal activity against some strains of P. aeruginosa, and the rapidly developing resistance of staphylococci, iv ciprofloxacin should not be used empirically for infections in settings (such as the intensive care unit) where these organisms are likely to be pathogenic. PMID- 8453177 TI - Lack of effect of influenza vaccine on anticoagulation by acenocoumarol. AB - OBJECTIVE: To analyze the effects of influenza vaccine on patients receiving chronic anticoagulant therapy with acenocoumarol. DESIGN: A prospective trial. SETTING: Hospital de la Santa Creu i Sant Pau, Barcelona. PATIENTS: Forty-three patients who received acenocoumarol, had stable levels of International Normalized Ratio (INR), and did not need dosage modification for four months before entering the study. INTERVENTION: A study of anticoagulation levels measured by INR at 7, 15, and 30 days from administration of the trivalent vaccine from the 91-92 campaign was conducted. MAIN OUTCOME MEASURES: Comparison was made between basal values (day 0) and anticoagulation levels at 7, 15, and 30 days from vaccine administration by means of a repeated-measures ANOVA. RESULTS: Nine patients (21 percent) had INR levels out of the therapeutic range during the study period. INR increased in three of these patients and decreased in six. There were no significant intraindividual changes in INR values during the time period analyzed (p = 0.125). No hemorrhagic or thrombotic manifestations occurred and no significant changes in renal or hepatic biochemistry were observed. CONCLUSIONS: Influenza vaccine does not modify acenocoumarol activity in patients receiving long-term anticoagulant therapy. PMID- 8453178 TI - Lowered serum phenytoin concentrations during therapy with liquid food concentrates. PMID- 8453179 TI - Appendicitis associated with loperamide hydrochloride abuse. PMID- 8453180 TI - Impotence associated with cinnarizine. PMID- 8453181 TI - Comment: how much is the Pharm. D. worth to a student? PMID- 8453182 TI - Chemotherapy for bladder cancer in the elderly. PMID- 8453184 TI - Treatment recommendations for respiratory tract infections associated with aging. AB - Age-related changes, for example reduced elasticity and earlier airways collapse, predispose the elderly to respiratory infection. Other factors such as a lifetime of smoking, the use of hypnotics, or the development of stroke also predispose. Pneumonia becomes increasingly common with advancing age, and both morbidity and mortality increase with associated disease burden. Diagnosis of pneumonia may be more difficult in the aged because of physiological changes. However, careful physical examination with accurate, regular recording of body temperature will usually reveal the characteristic features of pneumonia, which should be confirmed by chest radiograph. In the frail elderly, the onset of impaired function, such as confusion, immobility, falling or incontinence, should raise suspicion of infection. Pneumonia is classified as community-acquired, nursing home-acquired or nosocomial, which helps in the empirical choice of antibiotics. Streptococcus pneumoniae is the most common organism in the community, then Haemophilus influenzae and Branhamella catarrhalis. Gram-negative organisms like Klebsiella and Escherichia coli are more common in nosocomial infections. Nursing home patients with pneumonia tend to be more frail than those in the community. Treatment is directed at eradication of the organism with the appropriate antibiotic, maintaining hydration and oxygenation, as well as managing impaired mobility, faecal loading, urinary incontinence and confusion. Influenza vaccination is strongly recommended for the frail elderly. Tuberculosis remains an important diagnosis in the frail elderly and should always be considered, especially in patients with respiratory infection who fail to respond to conventional therapy. PMID- 8453183 TI - The effect of antihypertensive treatment on the quality of later years. AB - There is now a considerable body of evidence demonstrating the benefit of pharmacological therapy in reducing cardiovascular risk in elderly hypertensive patients. With the high prevalence of hypertension that exists in the elderly, the impact of the widespread use of antihypertensive treatment on the quality of life of older individuals requires consideration. Quality of life is a difficult concept to define and thus to measure scientifically. It is most commonly measured in clinical trials using questionnaire-based instruments designed to assess the subjects' perception of their own health and the degree of well-being and satisfaction in various health-related areas of their lives. Nonpharmacological methods of blood pressure reduction are generally regarded as being neutral or beneficial in their effects on quality of life, and deserve prolonged evaluation in elderly patients before introducing pharmacological therapy. The many antihypertensive drug treatments now available have varying impact on quality of life, which should be taken into account when developing a rational approach to antihypertensive intervention in the elderly patient. PMID- 8453185 TI - Musculoskeletal disease in the aged. Diagnosis and management. AB - Musculoskeletal diseases are the most prevalent conditions affecting the elderly today and cause significant suffering and disability in this population. The diagnosis of musculoskeletal disorders in older persons requires knowledge of the diseases which affect this age group, familiarity with the signs and symptoms, and a working knowledge of laboratory and radiographic abnormalities. Treatment of these disorders is based upon the principles of pain relief and maintenance of function. A multifaceted approach includes physical therapy, patient education, psychological support and the use of medications. Simple analgesics like paracetamol (acetaminophen) are gaining increased importance in the treatment of symptomatic disease. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most utilised pharmacological treatment and are effective in relieving pain and improving function in most patients. However, elderly persons are at increased risk for NSAID-induced toxicity, and drug choices should be made with this in mind. New data are becoming available as to the relative toxicity of the different NSAIDs, and this should help in choosing between these medications. Disease-modifying drug therapy is the most difficult to administer in elderly subjects. Potential toxicity must be weighed against realistic benefit in older persons prior to and during remittive therapy. With appropriate precautions, these agents can prove invaluable in the treatment of older persons with serious musculoskeletal disease. PMID- 8453187 TI - Mechanisms of age-related endocrine alterations. Part I. AB - Aging is associated with a myriad of hormonal changes. The mechanisms underlying these changes are variable. Aging is associated with anatomic changes of the endocrine glands, notably as a result of programmed cell death, autoimmune mediated destruction of the gland, or neoplastic transformation of glandular tissue. Age-related changes in hormonal secretion can also be secondary to physiological changes in circadian and seasonal rhythm, or in frequency or height of hormonal pulses. Some of these changes in hormone secretion are compensatory for the age-related reduction in hormonal clearance, and others are the results of changes in glandular sensitivity to secretagogues or inhibitory stimuli. Age related changes in hormone action can also be the result of altered bioactivity of hormones, altered transport of hormones to binding receptor sites, altered hormone-receptor interactions or due to postreceptor changes. Within the context of the latter, aging is associated with alterations in plasma membrane properties and intrinsic changes in cellular enzyme activity, and changes in calcium mobilisation and gene expression. Some of these changes are directly related to aging while others are secondary to age-associated diseases and changes in nutritional state. The predominant mechanism in each age-related change varies with the hormone studied. The age-related changes in the mechanisms of endocrine dysfunction are often tissue- and species-specific. Part II will discuss changes in hormone action with age. PMID- 8453186 TI - Free radical involvement in aging. Pathophysiology and therapeutic implications. AB - Free radical reactions are ubiquitous in living things. Studies on the origin and evolution of life provide a reasonable explanation for the prominent presence of this unruly class of chemical reactions. These reactions have been implicated in aging. Aging is the accumulation of changes responsible for the sequential alterations that accompany advancing age, and the associated progressive increases in the chance of disease and death. Aging changes are attributed to the environment and disease, and to an inborn process, the aging process. The latter produces aging changes at an exponentially increasing rate with advancing age. Improvements in general living conditions decrease the chance of death toward limiting values. Chances for death are now near these limits in the developed countries. Future significant increases in the average life span in the developed countries can only be achieved by slowing the rate of damage produced by the aging process. Support for the possibility that free radical reactions are responsible for the aging process now includes: i) studies on the origin of life and evolution; ii) studies on the effect of ionising radiation on living things; iii) dietary manipulations of endogenous free radical reactions; iv) the plausible explanations it provides for aging phenomena; and v) the growing numbers of studies that implicate free radical reactions in the pathogenesis of specific diseases. It is reasonable to expect on the basis of present data, that the average life expectancy at birth can be increased by 5 or more years by nutritious low caloric diets supplemented with one or more free radical reaction inhibitors. PMID- 8453189 TI - Mass attenuation coefficients, quantities and units for use in bone mineral determinations. AB - Theoretically determined mass attenuation coefficients for different bone mineral substitute materials together with values for water and fat are tabulated. The use of hydroxyapatite as a synonym for bone mineral is proposed. The abbreviation BMA (bone mineral areal mass) is suggested for use in conjunction with the unit g/cm2. Suggestions are also made for other quantities and units for use in reports of bone mineral measurements. PMID- 8453188 TI - Nilutamide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in prostate cancer. AB - Nilutamide is a nonsteroidal antiandrogen with affinity for androgen receptors but not for progestogen, estrogen, or glucocorticoid receptors. Consequently, nilutamide blocks the action of androgens of adrenal and testicular origin which stimulate the growth of normal and cancerous prostatic tissue. Nilutamide has a long half-life which permits once-daily administration. Nilutamide is usually given in combination with surgical or chemical castration using gonadotrophin releasing hormone (GnRH) [luteinising hormone-releasing hormone (LHRH)] agonists. In castrated patients the addition of nilutamide improves objective response rates, bone pain, urinary symptoms, tumour markers and time to disease progression. The tolerance of nilutamide is generally acceptable. Adverse effects are usually mild and reversible and consistent with androgen depletion. Unexpected but reversible adverse effects of nilutamide include delayed adaption to dark after exposure to bright light, transient increases in transaminases, and more severe but rare interstitial pneumonitis. Thus, nilutamide is a welcome treatment option that may be particularly useful in patients to whom the convenience of once-daily administration is seen as a worthwhile benefit. PMID- 8453190 TI - Screening for osteoporosis: comparison between dual energy X-ray absorptiometry and broadband ultrasound attenuation in 1000 perimenopausal women. AB - This paper compares dual-energy X-ray absorptiometry (DXA) of the spine and hip and broadband ultrasound attenuation (BUA) of the os calcis in 1000 perimenopausal women aged between 45 and 49 years who attended a randomized Osteoporosis Screening Programme. Significant correlations were found between all DXA results and BUA, with the trochanter giving the best numerical correlation with BUA (r = 0.354, p < 0.0001). BUA was not successful in predicting women with low DXA measurements, with only 44.0% of the women whose spinal DXA falls within the lowest quartile being in the lowest quartile of BUA. Although BUA is a poor predictor of spinal and hip bone mineral density it may provide additional structural information important in fracture prediction. PMID- 8453192 TI - Low bone mineral density, grip strength and skinfold thickness are important risk factors for hip fracture in Hong Kong Chinese. AB - The purpose of the study was to compare the bone mineral density (BMD) at the hip and spine, the grip strength and the skinfold thickness in Chinese hip fracture patients and controls, and to document the relative risk of hip fracture associated with different levels of these risk factors. The study was conducted on 163 elderly patients with hip fracture (32 men and 131 women) and 317 controls (104 men and 213 women). BMD at the hip and spine was measured by dual-energy X ray densitometry (Norland NR26). The mean grip strength was measured in both hands by a hand dynamometer; and bicep, tricep and iliac skinfold thicknesses were measured by a caliper (Holstain). Student's t-test was used to compare the mean bone densities, recalled body weight, grip strength and skinfold thickness; and multiple logistic regression was used to calculate the relative risk and 95% confidence intervals in quartiles of bone density, grip strength and skinfold thickness. In women, the mean BMD and anthropometric measurements were significantly lower in patients than controls. However, in men the mean recalled body weight and measured skinfold thickness were not significantly different between patients and controls. In both men and women the relative risk of hip fracture increased significantly with diminishing bone density at the spine, femoral neck and intertrochanteric area, but not at the Ward's triangle. In women the relative risk of hip fracture also increased significantly with a low recalled body weight, grip strength and skinfold thickness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8453191 TI - Effects of age and menopause on bone density of entire skeleton in healthy and osteoporotic women. AB - We studied 885 women to evaluate the effects of age and menopause on bone mineral density (BMD) in both healthy and postmenopausal osteoporotic subjects. The study cohort consisted of 161 healthy premenopausal women (age range 25-54 years), 357 healthy postmenopausal women (35-85 years) and 367 osteoporotic women (41-87 years). Total body and regional (spine, trunk, pelvis, arms, legs) BMD were measured with a dual-energy X-ray (DXA) device (Lunar DPX). Premenopausal BMD values remained essentially unchanged until the first half of the fourth decade, when they decreased. BMD values in both healthy postmenopausal and osteoporotic women were significantly lower than premenopausal values, and continued to decrease statistically after the onset of menopause. The highest Z-score (0.96 +/ 0.92) was found for total body BMD. Higher T-score values were found in osteoporotic than in normal postmenopausal women. In both healthy and osteoporotic postmenopausal women the best fits for BMD changes in total body, spine, trunk, arms and legs were obtained with the natural logarithm of years since menopause; only the pelvis BMD decreased linearly. Multiple regression analysis indicated that postmenopausal BMD changes in both normal and osteoporotic women were linked chiefly to body weight and years since the onset of menopause. PMID- 8453193 TI - The effect of low-dose cyclical etidronate and calcium on bone mass in early postmenopausal women. AB - This 2-year study was carried out in 36 healthy women of mean age 53.9 +/- 3.8 (SD) years and 3.4 +/- 2.3 years postmenopausal. Bone mineral density (BMD) in the spine, measured by single-energy quantitative computed tomographic scanning, gave a mean initial value of 110 +/- 26 mg/ml. The women were divided randomly into group 1 (n = 11), calcium 600 mg/day; group 2 (n = 15), calcium plus etidronate sodium 400 mg/day for 14 days every 3 months; and group 3 (n = 10), calcium plus etidronate plus phosphate, the 14-day etidronate course being preceded by phosphate 1 g twice daily for 3 days. During the first year of the study BMD decreased by 6.0 +/- 5.8% (p < 0.005) in group 1 subjects and increased by 4.5 +/- 7.8% (p < 0.005) in the combined etidronate-treated groups (difference between control and treated p < 0.001). Inclusion of phosphate in the regimen did not affect the response to etidronate. In the second year there was no significant mean change in BMD in any of the three groups. However, whilst there was little change in BMD values for most of the group 1 subjects, there was considerable variation in individual response within the etidronate-treated groups, with some subjects gaining and some losing bone. The change in BMD during the second year in the subjects as a whole was highly correlated with the change in plasma calcium after 3 months of treatment (r = 0.60, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8453194 TI - Influence of breastfeeding and other reproductive factors on bone mass later in life. AB - The influence of reproductive factors on bone mass at six skeletal sites was assessed in an age-stratified random sample of white women residing in Rochester, Minnesota. After age-adjustment, whether or not women had ever breastfed, total duration of breastfeeding and duration of breastfeeding per child were not associated with reduced bone mineral, but breastfeeding for more than 8 months was associated with greater bone mineral at some sites. There were no consistent effects on bone mineral, after adjusting for age, of gravidity or parity, age at menarche, age at first delivery, use of oral contraceptives or estrogen replacement therapy, various sex hormones, nor any of the other reproductive factors assessed. There was a strong protective effect of obesity, which was also correlated with a number of the reproductive variables. While animal studies suggest that pregnancy and lactation may be associated with calcium loss from the skeleton, these data indicate that such factors have little long-term impact on bone mass in humans and little potential for identifying women at high risk of osteoporosis later in life. PMID- 8453195 TI - Vertebral bone density in Icelandic women using quantitative computed tomography without an external reference phantom. AB - Vertebral trabecular bone mineral density (BMD) was measured in 187 healthy Icelandic women, age 35-64 years, by quantitative computed tomography (QCT) with the use of internal references (muscle and subcutaneous fat) instead of the traditional external references (phantoms). We found a mean 2.4 mg/cm3 (1.8%) bone loss per year in the age range 35-64 years. There was an accelerated phase (exponential) after menopause, with 4% loss per year for the first 1-5 years after menopause or 5-fold trabecular bone loss compared with the subsequent 11-15 years after menopause. Reproducibility was found to be 1.9%. This method thus compares with traditional QCT measurements and is highly reproducible. We find QCT using internal references a promising method for assessing fracture risk in perimenopausal women and for follow-up in osteoporotic patients. PMID- 8453196 TI - Relationships between bone structure in the iliac crest and bone structure and strength in the lumbar spine. AB - The purpose of this study was to examine the relationship between histomorphometric variables of cancellous bone structure and ultimate compressive strength (UCS) in the second lumbar vertebra (L2) and to determine whether structural variables in the iliac crest are predictive of the same variables and of UCS in L2. At autopsy, 7.5 mm diameter cores were removed from the iliac crest and from L2 of 29 subjects who had died suddenly without bone disease. Cancellous bone volume (BV/TV, %) was significantly lower in L2 than in iliac crest due to lower trabecular number (Tb.N, per mm) and thickness (Tb.Th, microns). There were significant correlations between iliac crest and L2 for BV/TV, Tb.N and trabecular separation (Tb.Sp, microns), but not for Tb.Th. BV/TV was negatively correlated, and Tb.Sp was positively correlated with age at both sites. Tb.Th was not significantly correlated with age in the iliac crest, but a significant negative correlation was observed in L2. The UCS of vertebral cores was negatively correlated with age. BV/TV and Tb.Th in L2 were positively correlated with UCS in L2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8453197 TI - Glucocorticoid-induced inhibition of osteoblastic bone formation in ewes: a biochemical and histomorphometric study. AB - The mechanisms underlying glucocorticoid-induced osteoporosis in humans are a defect in bone formation associated with increased bone resorption. The latter may be due to elevated parathyroid hormone (PTH) levels induced by the impairment of intestinal calcium absorption caused by corticosteroids. In this study we analysed the effects of corticosteroids in old ewes, a potential model for the study of human bone turnover. Two groups of seven 9-year-old female sheep were selected. The first group was injected intramuscularly with a daily dose of 30 mg methylprednisone (MP) during the first 2 months and 15 mg during the last month. After 2 and 3 months of treatment, blood samples were taken. At the end of the experiment the animals were slaughtered and the iliac crest kept for bone histomorphometry. Serum osteocalcin (sOC) rapidly and markedly decreased in the MP-treated group compared with controls (-77%; p < 0.01). In contrast, at the end of the experiment serum calcium and PTH levels were similar in both groups. Histomorphometric analysis showed a significant reduction in the wall width of trabecular packets. Dynamic parameters reflecting bone formation at the tissue and cell levels were significantly lower in the MP-treated group than in controls, with a highly significant decrease in the mineralization rate (MAR: 63%, p < 0.05) and double-labeled perimeter (dLPm/B.Pm: -92% p < 0.05). The bone formation rate (BFR/B.Pm) also decreased by 84% and the adjusted apposition rate (Aj.AR) by 80%. The increase in the total formation period was mainly due to an increase in the inactive period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8453198 TI - With Bach Flower Remedies life can take on deeper meaning. PMID- 8453199 TI - Challenges equal opportunities. PMID- 8453200 TI - The worst wounds need the best medicine. PMID- 8453201 TI - Near-infrared interactance in assessing superficial body fat in exclusively breast-fed, full-term neonates. AB - Near-infrared interactance was used to study changes in the percentage of superficial body fat in 91 healthy, breast-fed, full-term neonates during the first five days of life (group 1) and subsequently at two and four weeks of age in 28 infants (group 2). Near-infrared interactance was recorded as optical densities (ODs) at 937 nm and 947 nm. OD ratio agreed acceptably with fat content determined chemically in 16 pork meat samples. No correlation between OD ratio and skinfold thickness (measured at the same site in the subscapular area) was found. In group 1, no change was found in OD ratio, and maximum weight loss (at two days of age) was only 3%. In group 2, percentage of superficial body fat (estimated via OD ratios) increased by only 2%, despite normal weight gain (26% increase from birth weight). Breast feeding thus maintains adequate weight gain without accelerating superficial fat accumulation during the neonatal period. PMID- 8453202 TI - Dexamethasone in refractory seizures of premature infants. PMID- 8453203 TI - Diffuse neonatal haemangiomatosis in a newborn child. AB - Diffuse neonatal haemangiomatosis is a severe disease with a high mortality. It is characterized by multiple haemangiomas at birth affecting the skin and visceral organs. A case of diffuse neonatal haemangiomatosis in a newborn child with a favourable outcome after steroid treatment is described. PMID- 8453204 TI - Pericardial effusion complicating a percutaneous central venous line in a neonate. AB - A premature infant developed pericardial effusion four days after the insertion of a 25-gauge silastic percutaneous central venous catheter. The effusion contained parenteral nutrition fluid and resolved rapidly after withdrawal of the catheter. Pericardial effusion is a potential complication of percutaneous, as well as surgically placed, central venous catheters. PMID- 8453205 TI - Rapid diagnosis of the cause of pneumoperitoneum in ventilated asthmatic children. AB - Two asthmatic children developed a pneumoperitoneum whilst being mechanically ventilated. A quick and accurate diagnosis as to the cause of the pneumoperitoneum was made by analysing the partial pressure of oxygen in the intraperitoneal free gas. This analysis helped to diagnose an intestinal perforation in one child and an air leak from lung barotrauma in the other. There was minimal delay in the surgical treatment of the child with intestinal perforation and in the other, an unnecessary laparotomy was avoided. PMID- 8453206 TI - Renal function in hyperparathyroidism with complicating nephrocalcinosis. AB - Primary hyperparathyroidism in childhood is rare. Long-standing hypercalcaemia is reported to result in severe and irreversible renal damage. However, renal complications of hyperparathyroidism, particularly nephrocalcinosis are uncommon. We report a 12-year-old girl presenting after three years with extensive nephrocalcinosis and with rapid recovery of renal function. PMID- 8453207 TI - Pyomyositis and staphylococcal scalded skin syndrome. AB - Pyomyositis is a rare musculoskeletal infection in non-tropical countries. We report a child who had pyomyositis complicated by staphylococcal scalded skin syndrome. This complication has not previously been described in patients with pyomyositis. Early diagnosis of pyomyositis was made by ultrasound examination, and percutaneous needle drainage under ultrasound guidance was performed. Pus aspirated and blood cultures grew Staphylococcus aureus. No open surgical drainage was required and resolution of the abscess was documented by serial ultrasound examinations. PMID- 8453208 TI - "Covert toxocariasis" in a child treated with low-dose diethylcarbamazine. AB - A girl aged 2.5 years with "covert toxocariasis" was treated with low-dose diethylcarbamazine because of supposed noticeable disseminated Toxocara canis infection without ocular or visceral manifestations. There was marked blood and bone marrow eosinophilia, significant increased Toxocara canis antibody (ELISA) and immunoglobulins E, G and M, leucocytosis and an increased sedimentation rate. She had no geophagia, but often sucked small stones, probably contaminated with faeces from puppies. Symptoms were fever, inactivity, weakness, tiredness and loss of appetite. She was followed clinically and with blood samples throughout a period of three years and four months. PMID- 8453209 TI - D-lactic acidosis: a treatable encephalopathy in pediatric patients. AB - A 20-month old infant, who had short bowel syndrome following extensive surgery for a mid gut volvulus, developed hyperchloremic acidosis, with a large anion gap after enteral feeding was instituted. The organic acidosis was at least partly due to an increased concentration of D-lactic acid. This patient, as did five other pediatric patients, presented with a typical encephalopathy syndrome. Early recognition of this syndrome and treatment with an intestinal antibiotic and discontinuation of enteral feeding enabled prompt correction of the hyperchloremic acidosis and a rapid clinical recovery. PMID- 8453210 TI - Effects of partial plasma exchange transfusion on blood flow velocity in large arteries of arm and leg, and in cerebral arteries in polycythaemic newborn infants. AB - Continuous wave Doppler velocimetry was performed in brachial, femoral and cerebral arteries in four preterm, four small-for-gestational-age (SGA) and eight appropriate-for-gestational age (AGA) polycythaemic newborns before and at 3 and 24 h after partial plasma exchange transfusion and in 18 matched controls at 3 and 24 h after birth. In peripheral arteries, end-diastolic flow velocity was zero in all eight AGA controls, but only in two of the other infants. Consequently, mean flow velocity and red cell transport in AGA controls were significantly lower than in the other five groups, which did not differ. Partial plasma exchange transfusion did not influence flow velocities and red cell transport in peripheral arteries, but normalized the flow velocities in cerebral arteries in all three subgroups of polycythaemic infants, which were lower than in control infants. Cerebral red cell transport in controls increased significantly between 3 and 24 h, and in polycythaemic infants between 0 and 3 h after partial plasma exchange transfusion. In conclusion, reduction in haematocrit had different effects on blood flow velocity and red cell transport of peripheral and cerebral vessels, suggesting that the increased cerebral blood flow velocity after partial plasma exchange transfusion is not simply due to a reduction in viscosity or oxygen content of the blood. The lower peripheral blood flow velocities in normocythaemic AGA infants as compared to all other groups, suggest that the level of maturity is an important determinant for the capacity to regulate blood flow. PMID- 8453211 TI - Progressive systemic sclerosis sine scleroderma in a child presenting as nocturnal seizures and Raynaud's phenomenon. AB - Progressive systemic sclerosis sine scleroderma, as well as neurological manifestations of progressive systemic sclerosis are rare in adult-onset cases. Neither have been reported in children with progressive systemic sclerosis, either separately or together. We describe a six-year-old girl with nocturnal seizures and Raynaud's phenomenon of three years' duration. She died of cardiopulmonary sclerosis without ever fitting the required criteria of systemic sclerosis. Nailfold capillaroscopy revealed the specific "scleroderma-pattern" and provided the only clue for a diagnosis of progressive systemic sclerosis, confirmed eventually by skin biopsy. PMID- 8453212 TI - Autosomal recessive startle disorder. PMID- 8453213 TI - Incidence of celiac disease in northwest Stockholm. PMID- 8453214 TI - Effect of melanin, oxyhemoglobin and bilirubin on transcutaneous bilirubinometry. AB - To determine the effect of skin pigments on transcutaneous bilirubinometer readings, we measured the effect of bilirubin, melanin, and oxyhemoglobin solutions on transcutaneous bilirubinometer readings in vitro. Our results showed that the variability of the readings in vitro was related to the instrument's non linear response to bilirubin and melanin concentration and an inaccurate oxyhemoglobin correction factor. These factors should be considered in developing a more accurate non-invasive method of monitoring serum bilirubin concentration. PMID- 8453215 TI - Bilirubin bound to cells does not form photoisomers. AB - Cultured cells from one human and one murine cell line were incubated with bilirubin by different methods that allowed bilirubin to be bound to cells. The cells were irradiated with visible light of different wavelengths. Bilirubin bound to human serum albumin was also irradiated with light. After irradiation, bilirubin and its photoisomers were extracted and analyzed by HPLC. No photoisomers were found in samples of irradiated cells, while the types and amounts of photoisomers that were expected from the literature were found in samples of irradiated bilirubin/albumin mixtures. We conclude that the formation of therapeutically active photoisomers during phototherapy most probably does not take place in skin cells, but most likely in bilirubin bound to albumin in the vessels or in the interstitial space. PMID- 8453216 TI - The risk of bilirubin encephalopathy, as estimated by plasma parameters, in neonates strongly suspected of having sepsis. AB - The study comprises 18 mature newborns, strongly suspected of having sepsis, and a control group of 18 mature, healthy newborns with the same postnatal age. The object of the investigation was to compare the risk of development of bilirubin encephalopathy between the two groups, as estimated by plasma parameters. The sepsis group had significantly lower reserve albumin concentration for binding of MADDS (p < 0.01) and significantly lower total albumin concentration (p < 0.01). No significant differences were observed in unconjugated bilirubin concentration and plasma pH. It is suggested that mature newborns with sepsis have a slightly increased risk of developing bilirubin encephalopathy. PMID- 8453217 TI - Empiric red cell transfusion in asymptomatic preterm infants. AB - In a prospective randomized trial, asymptomatic very low-birth-weight infants in a neonatal intensive care unit were either electively transfused with red cells to maintain capillary haematocrit greater than 0.35 l/1 (group 1; n = 9), or were not transfused (group 2; n = 10). Individuals from both groups were excluded if they subsequently received non-elective transfusions, necessitated by their clinical condition. Electively transfused infants gained weight more rapidly than their non-transfused counterparts, but the duration of hospitalization was not shortened. Criteria of morbidity, such as patent ductus murmurs, apnoea and failure to thrive, were similar in both groups. We conclude that in the absence of clinical indications, transfusion to achieve a hematocrit greater than 0.35 l/1 as an empiric procedure, improves weight gain but the risks of transfusion are likely to outweigh the benefits. PMID- 8453218 TI - Comparison of the effects of phenobarbitone and morphine administration on EEG activity in preterm babies. AB - Continuously recorded amplitude-integrated EEG (aEEG) traces of 77 preterm babies were analysed retrospectively, to study the effect of different sedative drugs over a 24-h period. Thirty-seven babies were treated with phenobarbitone, 18 received morphine and 22 babies received no regular sedation. A "burst" was defined as a discharge of integrated amplitude greater than 10 microV and maximum interburst intervals in 10-min epochs over a 2-h period were measured. Maximum interburst was prolonged in babies given either morphine or phenobarbitone for sedation. Administration of a single dose of diazepam for intubation had a marked additive effect on the EEG depression caused by the base sedative and prolonged the effect for 11 to 12 h after drug administration. We conclude that the effect of sedative drugs must therefore be accounted for when interpreting records of quantified EEG for 12 to 24 h after drug administration. PMID- 8453219 TI - Extremely low-birth-weight infants less than 901 g. Growth and development after one year of life. AB - In a long-term prospective control study, 20 extremely low-birth-weight infants with birth weights between 500 and 900 g (mean 755 +/- 109 g) and gestational ages between 24 and 30 weeks (mean 26.2 +/- 1.8 weeks) were compared with 20 full term infants, after the first year of life for growth, development and continuing morbidity after discharge from the intensive care unit. The total rate of neurological abnormalities was 17%; the rate of infantile post-hemorrhagic hydrocephalus requiring shunt operations was 8.7%, while 13% had retinopathy of prematurity with vision deficit, but none was blind. The hospital readmission rate was 70%, but for most infants only one or a few readmissions were needed whereas three infants with chronic lung disorders required frequent hospital readmissions, mainly for respiratory infections. Apart from 4 infants with major cerebral neonatal complications, 16 of 20 extremely low-birth-weight infants (80%) showed development within the normal range at one year of age, although with delay in some areas in comparison with full-term control infants. Follow-up into preschool and school age is in progress. We cautiously suggest that the results at the one year follow-up do indicate a possible favourable long-term outcome for many of these extremely low-birth-weight infants with normal cognitive development and with no major neurological sequelae. PMID- 8453220 TI - Infantile hydrocephalus in preterm, low-birth-weight infants--a nationwide Swedish cohort study 1979-1988. AB - All Swedish infants with shunt-treated infantile hydrocephalus, born during the period 1979-88 at < or = 34 weeks gestational age and of low birth weight, were studied. Ninety-six infants were born before 32 weeks and 50 at 32-34 weeks. The mean gestational age in the very preterm group gradually decreased from 29.5 to 27.3 weeks. The mean live birth prevalence was 15.9 per 1000 very preterm infants, and 5.1 per 1000 moderately preterm infants. No significant secular prevalence trends were found. The perinatal mortality decreased successively. The slowly decreasing trend in moderately preterm infants may imply better outcome in survivors. The slightly increasing trend in very preterm infants could be explained by more survivors in the low gestational age group. The aetiology was considered perinatal in 94% of the very preterm group and in 56% of the moderately preterm group; prenatal in 1% and 32% of infants, respectively. Additional neuro-impairments were present in 82% of infants, cerebral palsy being the commonest (74%). PMID- 8453221 TI - Oral versus intravenous premedication for small bowel biopsy in children: effect on procedure and fluoroscopy times. AB - Oral alimemazine and cisapride, or diazepam and cisapride, or iv midazolam and metoclopramide were given as premedication for small bowel biopsy to three groups of children from a total population of 185 individuals. The biopsy procedures were performed under intermittent fluoroscopy and times for both were recorded. The median biopsy procedure time was significantly shorter in children given iv midazolam and metoclopramide (6 min) compared to those given oral premedication (10 min) (p < 0.001). The median fluoroscopy time was very short in all groups, ranging between 3 and 6 s. It is concluded that iv premedication is superior to oral premedication for small bowel biopsy in children because more effective sedation is obtained. PMID- 8453222 TI - Clinical experience with a hypotonic oral rehydration solution in acute diarrhoea. AB - A hypotonic oral rehydration salts (ORS) solution with total osmolality of 224 mosmol/l was compared in an open clinical trial with an isotonic (osmolality 304 mosmol/l) ORS solution for the treatment of dehydration due to acute diarrhoea. Both ORS solutions had the same electrolyte composition with a Na+ concentration of 60 mmol/l. Children given the hypotonic ORS solution (n = 103) passed significantly fewer diarrhoeal stools, and their diarrhoea and hospital stay were shorter than those of children given the isotonic ORS solution (n = 135). We conclude that hypotonic ORS ("light" ORS) has clinical advantages over the standard ORS currently used in Finland. PMID- 8453223 TI - Diagnosis of the carbohydrate-deficient glycoprotein syndrome by analysis of transferrin in filter paper blood spots. AB - Carbohydrate-deficient glycoprotein syndrome is a recently identified recessively inherited, multisystemic disease with severe nervous system involvement. It is characterized biochemically by carbohydrate-deficient serum glycoproteins, and can be diagnosed by analysis of abnormal isoforms of serum transferrin. Using stored, neonatally collected filter paper blood spots from such patients, it was shown that neonatal diagnosis was possible by immune-isoelectric focusing of transferrin eluted from up to 14-year-old samples. Freshly collected blood on filter paper was readily analyzed quantitatively for carbohydrate-deficient isotransferrins by a rapid microchromatographic assay, revealing highly elevated values in all patients. The presently described methods thus provide a means for early diagnosis of the carbohydrate-deficient glycoprotein syndrome in microliter volumes of capillary blood. Sampling on filter paper offers an important simplification in sample collection, storage and transport, and may make population studies possible. PMID- 8453224 TI - A community-based prospective incidence study of epileptic seizures in children. AB - During a 20-month period, an attempt was made to find all children with unprovoked non-febrile seizures. The first attendance and incidence rates were 95 and 89/100,000, respectively, in the age group 0-15 years. These figures are lower than those found 10 years earlier in the same area. The highest incidence was during the first year of life and there was a higher proportion of girls (male:female ratio 1:1.4). Generalized seizures dominated in the first year of life. The incidence of benign childhood epilepsy with centro-temporal spikes was 10.7/100,000 and was the most common epilepsy syndrome found. The incidence of partial seizures increased with age up to the age of 10 years. One in 10 children had a history of febrile convulsions. PMID- 8453225 TI - Seizures as the presenting symptom of brain tumors in children. AB - Epileptic seizures caused by tumors in children have been regarded as uncommon. We have studied 99 consecutive cases of brain tumors during the period 1980-1987. In 20 cases the tumor was localized to one of the hemipheres and 10 of the cases had seizures, in 9 as the only initial symptom. Details of the clinical picture and the course are presented. Delay from initial symptoms to correct diagnosis was considerable in 4 cases--more than six years. The factors mainly responsible for this delay were: initial EEG normal or soon normalized, misinterpretation of computerized tomography and seizure freedom with or without antiepileptic drug treatment. We conclude that regional slowing in the EEG is a common, although not obligatory, finding. Computerized tomography should be performed in all children with newly presented epilepsy of partial type, except for those with benign partial epilepsy with centro-temporal spikes. PMID- 8453226 TI - Mental health and psychosocial functioning in adolescents with congenital heart disease. A comparison between adolescents born with severe heart defect and atrial septal defect. AB - Twenty-six adolescents, aged 13-18 years, with severe congenital heart disease were matched for sex, age and living area with 26 adolescents with repaired atrial septal defect and regarded as physically fit. These two groups were compared according to somatic condition, psychopathology, psychosocial functioning and chronic family difficulties. A higher rate of psychiatric problems in the complex group, an association between psychosocial functioning and physical capacity, as well as an association between psychosocial functioning and chronic family difficulties were observed. These findings suggest that physical capacity is of crucial importance for mental health and functioning of adolescents with congenital heart disease. The association with chronic family difficulties also suggests that a comprehensive biopsychosocial approach is necessary in the treatment and rehabilitation of these patients. PMID- 8453227 TI - Trunk asymmetry and screening for scoliosis: a longitudinal cohort study of pubertal schoolchildren. AB - A cohort of children was followed-up annually from an average age of 10.8-13.8 years to assess various measures of trunk asymmetry for their predictive value in the screening of scoliosis. Of 1060 children, 855 (80.7%) participated in the final examination. Trunk asymmetry was measured by the forward bending test and moire topography. A posteroanterior standing radiograph of the spine was taken of those 250 (29.2%) children who had a trunk hump > or = 8 mm. Only 8.3% of the children were found to be symmetric (hump 0-2 mm) in the forward bending test: 65.5% had a hump of 3-7 mm and 26.2% had a hump > or = 8 mm at 13.8 years. Also, moire fringe asymmetry proved to be common (prevalence of asymmetry > 1 fringe 47.3%), but its correlations with rib hump (r = 0.16) and Cobb angle (r = 0.12) were low. At the final examination, the prevalence of scoliosis (Cobb angle > or = 10 degrees) was 9.2%. Two girls (0.2%) needed brace treatment. The forward bending test is preferable to moire topography in screening for scoliosis, and a hump size of 6 mm at an average age of 10.8 years is the nearest to optimal as a screening threshold. PMID- 8453228 TI - Evaluation of attempted prevention of unexpected infant death in very high-risk infants by planned health care. AB - Three hundred and ninety-six babies born in Sheffield between 1982 and 1990 identified as being at "very high risk" of unexpected infant death by means of a scoring system, received an intensive programme of health care including a case discussion between a paediatrician, the GP and the health visitor held in the family doctor's surgery, weekly visits from the health visitor and informal hospital admission. Significantly fewer sudden unexpected infant deaths occurred in this group than were expected by logistic regression analysis or occurred in the best available control group with comparable scores (p = 0.024). Problems in evaluation include identification of an adequate control population, ethical difficulties in introducing a controlled study when the programme is already perceived as effective, and the calculation of "expected death rates". The results of this study indicate that very energetic programmes of intervention may prevent some deaths in vulnerable infants. PMID- 8453229 TI - Towards an equal distribution of health? Socioeconomic and regional differences of the secular trend of the age of menarche in Finland from 1979 to 1989. AB - The purpose of this study was to investigate if a secular trend towards an earlier age of menarche still existed in Finland in the 1980s and if social class and regional differences observed previously in the mean age of menarche had disappeared. Questionnaires were mailed to nationwide representative samples of 16- and 18-year-old girls every other year from 1979 to 1989. At the national level, the secular trend towards an earlier menarche was not observed in the 1980s but the trend was significant among girls living in the North-West and rural areas. Clearly observed regional and urban-rural differences in 1979 disappeared in the 1980s. Social class differences persisted: farmers' daughters had a higher mean age of menarche than those of other occupational groups. Adolescents in the 1980s displayed a more even distribution of health than the cohorts born before them. Improved welfare of the Finnish society and reorganization of the primary health care are probable explanations. PMID- 8453230 TI - The effectiveness of eye protection during high-intensity phototherapy. PMID- 8453231 TI - Effects of theophylline on plasma lipids in low-birth-weight infants (< or = 1250 g). PMID- 8453232 TI - Increased serum levels of antigliadin antibodies in cystic fibrosis. PMID- 8453233 TI - Low serum cholesterol in children with fever. PMID- 8453234 TI - Short-term prophylaxis of febrile convulsions by oral diazepam. PMID- 8453235 TI - The legacy of Karen Ann Quinlan. PMID- 8453236 TI - The insane root takes reason prisoner: the supreme court and the right to die. PMID- 8453237 TI - Intimacy and caring: the legacy of Karen Ann Quinlan. PMID- 8453238 TI - Getting beyond suspicion of homicide: reflections on the struggle for morally appropriate care of the dying under high technology medical care. PMID- 8453239 TI - Re-thinking consent. PMID- 8453240 TI - Permanently unconscious patients: some personal reflections. PMID- 8453241 TI - HIV infected pharmacist must have unrestricted job or hospital will lose millions... PMID- 8453242 TI - Shaping a participatory democracy in health care. PMID- 8453243 TI - There must be a way ... defining a role for ethics committees in health care decision making. PMID- 8453244 TI - The Ombudsman experience: administrative protection for vulnerable patients. PMID- 8453245 TI - Family role in health care decision making. PMID- 8453246 TI - From the families... PMID- 8453247 TI - The significance of the legacy of Karen Ann Quinlan. PMID- 8453248 TI - The legacy of Karen Ann Quinlan: a nurses' perspective. PMID- 8453249 TI - Humor in the management of serious medical disorders. PMID- 8453250 TI - Ethics committee casebook. PMID- 8453251 TI - From the desk for: risk management ... IV conscious sedation: essential techniques of monitoring. PMID- 8453252 TI - The doctrine of informed consent. PMID- 8453253 TI - Infections in splenectomised patients: guidelines for management. PMID- 8453254 TI - Development of thyroid gland volume during the first 3 months of life in breast fed versus iodine-supplemented and iodine-free formula-fed infants. AB - The spontaneous development of thyroid gland volume (TGV) during the first 3 months of life was studied in entirely breast-fed infants (n = 21) and compared to those fed an iodine-supplemented formula (n = 19), an iodine-free formula (n = 5), or partially breast-fed in addition to an iodine-free (n = 4) or an iodine supplemented formula (n = 16). The TGV of the infants and their mothers was determined sonographically in addition to their urinary iodine concentrations 5-7 days postpartum and 3 months later. In ten additional lactating mothers the breast milk concentrations of thyroid hormones and iodine were determined. It was shown that at 3 months of age an infant consuming about 1000 ml breast milk per day receives about 2 micrograms thyroid hormones and 55 micrograms iodine per day. At the end of their first week of life the infants showed a TGV between 0.28 and 1.5 ml (median 0.61 ml) and a urinary iodine concentration between 0.03 and 16.3 micrograms/dl (median 3.0 micrograms/dl). At 3 months of age the TGV of the breast-fed infants had decreased by a median of 0.24 ml (= -34%; median of percentage changes) whereas those fed a formula without iodine had increased by a median of 0.26 ml (= +50%; median of percentage changes). Those receiving an iodine-supplemented formula showed a TGV reduction of 0.14 ml (= +2%; median of percentage changes). The TGV development of the partially breast-fed infants lay between those being exclusively breast or formula fed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8453255 TI - Analogous effects of serum lipids from patients with nonthyroidal illness and normal subjects on the uptake of thyroxine and its conversion to triiodothyronine by rat hepatocytes in culture. AB - The low level of triiodothyronine (T3) in nonthyroidal illnesses (NTI) has been attributed to the decreased peripheral conversion of thyroxine (T4) to T3; patient's serum lipids decreased the conversion in a cell-free system. The objective of our study was to determine whether patients' serum lipids, whose content was elevated 2.5-fold above the reference serum value, and oleic acid affected the uptake of T4 and its conversion to T3 by rat hepatocytes in culture, thereby providing information on the cell's response to these processes. Serum ether extracts and oleic acid (0.1 mumol/l) were incubated with cells followed by assessment of T4 uptake and conversion of T4 to T3. The mean T4 uptake in the presence of ether extracts of NTI patients' or normals' sera were similar (112 +/ 15% and 110 +/- 24%, respectively). There was no difference in the T4 to T3 conversion between the patient and normal groups (90 +/- 14%); oleic acid also did not influence the conversion (96.7 +/- 1.6%). Uptake and conversion in the absence of either extracts and oleic acid were controls. These results suggest that serum lipids from NTI patients and normal subjects exercise qualitatively and quantitatively almost similar influences on T4 uptake and its conversion to T3; oleic acid is not an inhibitor of T4 uptake and T4 to T3 conversion in the rat hepatocyte. Since hepatocytes actively process fatty acids, their influence on intracellular conversion of T4 is not equitable with T4 conversion using the cell-free system. Our results do not support the hypothesis that abnormal lipid metabolism in NTI impairs hepatic T4 to T3 conversion. PMID- 8453256 TI - Poor plasma status of carotene and vitamin C is associated with higher mortality from ischemic heart disease and stroke: Basel Prospective Study. AB - Previous cross-cultural comparisons of the mortality from ischemic heart disease in European communities with associated plasma levels of essential antioxidants have revealed strong inverse correlations for vitamin E and relatively weak correlations for other antioxidants. Similarly, in a case-control study in Edinburgh low plasma levels of vitamin E were significantly associated with an increased risk of previously undiagnosed angina pectoris whereas low levels of other essential antioxidants lacked statistical significance. The current Basel Prospective Study is particularly well suited to elucidate the impact of antioxidants other than vitamin E. In this population (which was recently evaluated regarding cancer mortality) the plasma levels of vitamins E and A are exceptionally high and above the presumed threshold level of risk for ischemic heart disease. The present 12-year follow-up of cardiovascular mortality in this study reveals a significantly increased relative risk of ischemic heart disease and stroke at initially low plasma levels of carotene (< 0.23 mumol/l) and/or vitamin C (< 22.7 mumol/l), independently of vitamin E and of the classical cardiovascular risk factors. Low levels of both carotene and vitamin C increase the risk further, in the case of stroke even with significance for overmultiplicative interaction. In conclusion, in cardiovascular disease independent inverse correlations may exist for every major essential antioxidant although the latter can also interact synergistically. Therefore future intervention trials of antioxidants in the prevention of ischemic heart disease should primarily test the simultaneous optimization of the status of all principal essential antioxidants. PMID- 8453257 TI - Levels of parathyroid hormone-related protein in hypercalcemia of malignancy: comparison of midregional radioimmunoassay and two-site immunoradiometric assay. AB - Overproduction of parathyroid hormone-related protein (PTHrP) is a major cause of hypercalcemia of malignancy in patients with solid tumors. We measured plasma levels of the protein by a radioimmunoassay (RIA) against PTHrP(53-84) and by an immunoradiometric assay (IRMA) against PTHrP (1-86). Of 16 affected patients 7 had elevated PTHrP levels in both assays and 4 had elevated levels in the RIA only. Median levels were about tenfold higher in these patients when measured by RIA (median of 34 versus 2.2 pmol/l). Measurements from both assays were, however, highly correlated with each other in this patient group (P < 0.01). PTHrP was not elevated in 10 normocalcemic patients with lung carcinoma. During long-term follow-up of a patient with a mesothelioma of the pleura, PTHrP levels measured with both assays decreased during chemotherapy in parallel with a normalization of serum calcium. In another hypercalcemic patient suffering from renal carcinoma, PTHrP measured by IRMA decreased by 40% within 12 h after nephrectomy, whereas PTHrP measured by RIA did not show a significant decline. Direct comparison of the assay results thus pointed to the existence of heterogeneity of circulating forms of PTHrP in plasma. In conclusion, both immunoassays detected elevated levels of PTHrP in a fraction of patients with hypercalcemia of malignancy and thus may be a tumor marker during treatment of malignancies. PMID- 8453258 TI - Weight loss in patients with hematological neoplasias is associated with immune system stimulation. AB - Weight loss is the main symptom of so-called tumor cachexia. The pathogenetic mechanisms underlying cachexia are poorly understood; however, it appears that enhanced formation of cytokines such as interferon-gamma and tumor necrosis factor-alpha are involved. In 94 patients suffering from hematological neoplasias we compared body weight changes with serum neopterin, tryptophan, and kynurenine. Biochemical changes, the formation of neopterin, the degradation of tryptophan are closely related to interferon-gamma activity. The majority of our patients had increased neopterin and decreased tryptophan concentrations. Weight loss was seen particularly in patients with higher neopterin and lower tryptophan values. An association between higher neopterin levels and greater weight loss was apparent at study entry and during the follow-up of patients. Our data support the concept that weight loss is closely linked to endogenous interferon-gamma activity. PMID- 8453259 TI - A preparation from bovine colostrum in the treatment of HIV-positive patients with chronic diarrhea. AB - In a prospective, open, uncontrolled study 25 patients infected with the human immunodeficiency virus with chronic refractory diarrhea and either confirmed cryptosporidiosis (n = 7) or absence of demonstrable pathogenic organisms (n = 18) were treated with a daily oral dose of 10 g of an immunoglobulin preparation from bovine colostrum over a period of 10 days. Among the 7 patients with cryptosporidiosis, this treatment led to complete remission in 3 and partial remission in 2. Among the 18 patients with diarrhea and negative stool culture, complete remission of diarrhea was obtained in 7 and partial remission in 4. In the remaining 2 patients with cryptosporidiosis and the 7 patients with diarrhea but no demonstrable pathogens treatment produced no significant improvement of the diarrhea. Subsequent doubling of the Lactobin dose (2 x 10 g daily) in 8 of the nonresponders led to complete remission in one case and at least partial remission in a further 4 patients. Treatment of refractory diarrhea with 10 g immunoglobulins from bovine colostrum per day constitutes an important therapeutic approach and led to complete (40%) or partial (24%) remission of diarrhea in 64% of the patients described here. PMID- 8453260 TI - Cerebral ischemia induced by compression tests during transcranial Doppler sonography. AB - Compression tests performed during transcranial Doppler sonography are intended for support in identifying vessels and measuring collateral circulation within the circle of Willis. The resulting information is thought to be valuable in patients with extracranial carotid stenoses, especially for planning carotid and extra-/intracranial bypass surgery. In a retrospective analysis of a series of 380 cases, two patients with symptomatic carotid artery stenoses suffered three compression-induced focal cerebral ischemias. In two instances, these ischemias started under compression. The resulting deficits were reversible. One patient developed an additional and persisting motor deficit whose onset was delayed. The diagnostic benefit of compression tests is not established nor its risk well defined. They should not be used routinely. PMID- 8453261 TI - Subarachnoid hemorrhage as presenting feature of isolated neurosarcoidosis. AB - A 35-year-old man presented with the clinical picture of spontaneous subarachnoid hemorrhage. Four weeks after the first symptoms he noticed blurred vision, and ophthalmological examination detected bitemporal hemianopia. At this time cerebral computed tomography and magnetic resonance imaging showed enlargement of the optic chiasm, and visual evoked potentials revealed delayed latencies. In the cerebrospinal fluid cells and protein content were elevated, and angiotensin converting enzyme was detectable. Under steroid treatment the patient recovered completely and computed tomography, magnetic resonance imaging, visual evoked potentials, and cerebrospinal fluid findings became normal. Although a great variety of neurological symptoms may occur in neurosarcoidosis, to our knowledge spontaneous subarachnoid hemorrhage as the presenting feature has never been reported before. PMID- 8453262 TI - Neopterin and opportunistic infections in HIV-infected patients. PMID- 8453263 TI - Passive smoking and lung function in asthmatic children: a commentary. PMID- 8453264 TI - Halofantrine: a new substance for treatment of multidrug-resistant malaria. PMID- 8453265 TI - The use of gemfibrozil in a patient with chronic myelogenous leukemia to successfully manage retinoid-induced hypertriglyceridemia. AB - Systemic retinoids are used in the management of chronic cutaneous conditions and life-threatening dermatoses. Unfortunately, drug-induced hypertriglyceridemia may necessitate either dose reduction or discontinuation of therapy. The purpose of this article is to describe the successful management of isotretinoin-induced hypertriglyceridemia with gemfibrozil in a leukemia patient. Sequential serum chemistries were performed prior to, during, and following treatment with a systemic retinoid and a lipid-regulating agent. A prompt and sustained normalization of fasting triglycerides occurred following the initiation of gemfibrozil in a patient with isotretinoin-induced hypertriglyceridemia. When retinoids are being used in the management of serious conditions, the initiation of therapy with gemfibrozil to reduce the elevated triglycerides may be appropriate in those patients with retinoid-induced hypertriglyceridemia. PMID- 8453266 TI - Gaucher's disease: therapy by intravenous infusions of modified glucocerebrosidase. PMID- 8453267 TI - Recent advances in retrovirus vector technology. AB - Retroviral vectors are widely used for the study of retroviral replication and to introduce DNA into somatic cells. An exciting new approach in retroviral vector technology is the use of internal ribosome entry sites from picornaviruses to provide stable expression of multiple genes. In addition, strategies are being developed that target the expression of retroviral vectors to specific cell populations. PMID- 8453268 TI - Retroviruses: delivery vehicle to the liver. AB - Liver-directed gene therapy holds great promise for the treatment of inherited metabolic disease. Two strategies have emerged. Ex vivo gene therapy involves the transplantation of autologous hepatocytes transduced with recombinant retroviruses while in culture. The feasibility of this approach has been demonstrated in several animal models, and a human trial has been initiated. An alternative strategy uses recombinant viruses to deliver the transgene directly to hepatocytes in vivo. PMID- 8453269 TI - Retroviral lineage studies: some principals and applications. AB - Retroviral vectors have been widely employed in gene transfer studies in higher organisms. One application has been in cell lineage studies. The last several years have seen the extension of simple viral marking to include other strategies such as cell purification and in vitro manipulation. PMID- 8453270 TI - Oncogenes and cell proliferation. PMID- 8453271 TI - Viral genetics. PMID- 8453272 TI - Abl tyrosine kinase in signal transduction and cell-cycle regulation. AB - Although the biological function of the c-Abl tyrosine kinase remains unsolved, potentially productive avenues towards the elucidation of that function have been identified by recent progress. An F-actin binding and a sequence-specific DNA binding domain have been discovered in c-Abl, and DNA binding has been shown to be cell-cycle regulated. Deletion of those two domains in the mouse c-Abl results in a loss of biological function despite the production of an active tyrosine kinase. These findings suggest a role for c-Abl in the regulation of processes occurring on F-actin and on specific DNA elements. PMID- 8453273 TI - The role of c-myc in cell growth. AB - Recent experiments have established that the c-myc oncogene encodes a sequence specific DNA-binding protein that interacts with a specific intracellular partner, Max, and probably manifests its effects through transcriptional modulation. In addition, the range of biological functions attributed to expression of c-myc has grown to include not only transformation and mitogenesis but also cell death. PMID- 8453274 TI - Cyclin D and oncogenesis. AB - The D-type cyclins are among the candidate 'G1 cyclins' in higher eukaryotes that may regulate G1-S-phase progression. The human cyclin D1 gene, also known as PRAD1 (and previously as D11S287), is a putative proto-oncogene strongly implicated in several types of human tumors, including parathyroid adenomas, B cell neoplasms (as the 'BCL-1 oncogene'), and breast and squamous cell cancers. The mechanism by which deregulated production of cyclin D1/PRAD1, and perhaps other D-type cyclins, contributes to tumor development is only beginning to be deciphered. PMID- 8453275 TI - Tumor-suppressor p53 and the cell cycle. AB - The p53 tumor suppressor is a transcription factor that can activate the expression of some genes and repress the transcription of others. The protein appears to be dispensable for normal murine development, although mice lacking p53 develop tumors at an early age and their fibroblasts are genetically unstable in culture. Human and murine cells lacking wild-type p53 loose the ability to arrest in the G1 phase of the cell cycle in response to gamma-irradiation. Therefore, p53 may be a cell-cycle checkpoint protein that regulates the cycle under adverse conditions. PMID- 8453276 TI - Retinoblastoma protein and the cell cycle. AB - Deregulation of the cell cycle may contribute one of the primary mechanisms through which cancer arises. Eukaryotic cell division has been found to be a strictly controlled process, involving response to both positive and negative external signals and assessment of the cell's internal state. Several recent discoveries have strengthened and refined the theory that the retinoblastoma protein is involved in the decision between cell division and differentiation, and have begun to provide an outline of the nature of this involvement. PMID- 8453277 TI - DNA tumor virus transforming proteins and the cell cycle. AB - Studies using the transforming proteins of the small DNA tumor viruses point to the role of the E2F cellular transcription factor in regulating cell cycle specific gene expression. The evidence derived suggests that E2F is controlled by the retinoblastoma gene product and related proteins, including their associated cyclins. Studies using DNA tumor virus products further suggest the existence of additional pathways of cell-cycle activation. PMID- 8453278 TI - Poxvirus vectors: cytoplasmic expression of transferred genes. AB - During the past year there have been a number of advances in poxvirus vector design and application. These include improvements in gene expression and a direct method of inserting DNA into the poxvirus genome. Alternative methods of selecting recombinant viruses have been developed, and attenuated and non replicating vaccinia virus and avian poxvirus vectors are now being used successfully. Field trials of an oral, wild-life rabies vaccine, and phase 1 testing of human vaccines derived from vaccinia virus are in progress. This review is an updated and modified version of a review first published in Current Opinion in Biotechnology 1992, 3:533-539. PMID- 8453279 TI - Geminiviruses: plant viral vectors. AB - Geminiviruses are being used as convenient autonomously replicating vectors for foreign gene amplification in plants. Using tissue culture techniques, they have been adapted for the analysis of the regulation of gene expression in a wide range of hosts, including both mono- and dicotyledonous species. In monocotyledonous plants that are particularly recalcitrant to transformation, geminivirus symptom-induction has been used as a sensitive marker for DNA uptake. PMID- 8453280 TI - Baculoviruses: high-level expression in insect cells. AB - Baculoviruses continue to serve as workhorse vectors for the high-level expression of eukaryotic genes in insect cells; however, numerous researchers are also finding novel uses for these vectors by taking advantage of the unique nature of the viruses and their host cells. Concurrently, the technology involved in constructing and utilizing these vectors is being improved so that the time and effort required to construct expression vectors are reduced. PMID- 8453281 TI - Rapid dynamic changes in adult cerebral cortex. AB - While the plasticity of cortical connections has long been known to be a property of developing cortex, a new view of cortical function reveals a substantial degree of mutability of receptive field properties and cortical topography. The most recent studies show that the dynamic properties of cortex can be observed over a time scale of minutes. PMID- 8453282 TI - A neural circuit specialized for vocal learning. AB - The anterior forebrain circuit of the songbird brain has been known for some time to play a special role in song learning. Recent work has strengthened this view and has begun to describe the specific properties of this pathway. The development of the circuit early during song learning, its auditory responsiveness, and its synaptic interaction with the vocal motor pathway all suggest that it is involved in the sensory learning and auditory-motor matching essential to normal song development. Behavioral studies point to a variety of mechanisms of action of this pathway and suggest that it is one site for steroid hormonal effects on vocal motor plasticity. Investigation of the anterior forebrain circuit promises to clarify its role in learning and to elucidate the cellular mechanisms involved. PMID- 8453283 TI - Development. PMID- 8453284 TI - Signal transduction pathways in neuronal differentiation. AB - New insights into the signal transduction pathways for neuronal growth factors and cell adhesion molecules are affording us a better understanding of the intracellular mechanisms for neuronal differentiation, and of the ways in which the various signals are integrated during this process. PMID- 8453285 TI - Cell death genes in invertebrates and (maybe) vertebrates. AB - That naturally occurring cell death in the nervous and other systems is an active and physiologically appropriate process has received much attention recently and has gained a significant degree of acceptance. The identification of cell death genes in invertebrates, the characterization of gene products that function as cell death suppressors, and the demonstration that some proto-oncogenes elicit cell death, as well as proliferation, in certain cell types have heightened interest in the mechanism of programmed cell death. Yet, evidence for a genetic program for cell death in vertebrates remains circumstantial and, so far, vertebrate 'cell death' genes exist only in theory. PMID- 8453286 TI - Hair cell development. AB - Neurobiologists have been challenged by the desire to understand how the highly specialized ultrastructure of the sensory hair cells of the ear develops, how patterns of phenotypically distinct hair cells are formed and regenerate, and how their specific neural connections are formed. Recent research has addressed some of these challenges at the level of cell and molecular biology, focusing on cell proliferation in hair cell epithelia, the mechanisms that control hair cell differentiation, and the developmental interdependencies between hair cells and neurons. The initial identification of some of the homeobox genes and growth factors that are involved in hair cell development has occurred during the past year. PMID- 8453287 TI - The role of migration in central nervous system neuronal development. AB - The past year has seen the emergence of significant new information on the control of neurogenesis and migration, and the establishment of neuronal identity in three systems: developing cerebellum, cortex, and optic tectum. These findings have important implications for the role of glial-guided migrations in central nervous system neuronal development. PMID- 8453288 TI - Cell signalling in induction and anterior-posterior patterning of the vertebrate central nervous system. AB - Recent experimental studies in the Xenopus embryo have led to a reappraisal of the mechanisms by which the neural plate is induced and patterned by dorsal mesoderm. This review focuses on these, and related studies, addressing the role of cell signalling in patterning the vertebrate central nervous system. PMID- 8453289 TI - Pathfinding at the mammalian optic chiasm. AB - Axons of retinal ganglion cells in the eye form a system of retinal projections, which carry information about the world around us to targets in the brain for processing. Recent work combining video imaging technology, manipulations of mouse embryos in vivo, and molecular approaches have begun to shed light on how this major sensory pathway in the mammalian brain comes about during embryonic development. PMID- 8453290 TI - Topography in the Drosophila visual system. AB - The Drosophila visual system offers an excellent opportunity for studying the development of proper retinotopic connections at the level of individual identifiable cell types. Recent work suggests that, despite obvious anatomical and developmental differences, at least some of the general developmental strategies operating in the Drosophila visual system parallel observations made previously for vertebrates. The extensive repertoire of powerful genetic and molecular techniques available in Drosophila can now be directed towards determining whether these parallels also reflect similarities in the underlying molecular mechanisms. PMID- 8453291 TI - Intracellular associations of adhesion molecules. AB - Significant advances have recently been made in our understanding of the cytoplasmic anchorage of adhesion molecules. The identification of catenins, a new class of proteins involved in the cytoplasmic anchorage of cadherins that are structurally homologous to other peripheral cytoplasmic proteins, emphasizes the existence of protein families that modulate the function of cell-substrate and cell-cell adhesion molecules. PMID- 8453292 TI - Topographic maps and molecular gradients. AB - Topographically organized patterns of connectivity occur throughout the central and peripheral nervous systems. It is commonly supposed that gradients of recognition molecules underlie this form of synaptic specificity. Recent studies have led to new ideas about how such gradients might arise in the retinotectal system, and initiated molecular analyses of position-dependent gene expression in the peripheral motor system. PMID- 8453293 TI - Development of the neuromuscular synapse. AB - Major advances have occurred in our understanding of the signaling events involved in neuromuscular synapse formation. In particular, it has recently been shown that agrin is necessary for synapse formation, that acetylcholine receptor genes are specifically transcribed by synaptic nuclei in response to signals from the synaptic basal lamina, and that synaptic competition between motor neurons can occur by a Hebbian mechanism in cell culture. PMID- 8453294 TI - Cell and molecular biology of neural crest cell lineage diversification. AB - Neural crest cells are multipotent progenitor cells, but it is not understood how these cells generate their diverse differentiated progeny. This review considers the issues of whether neural crest cells self-renew, whether they generate partially committed intermediate progenitors, and how the local embryonic environment may act to control this diversification process. Novel molecular markers for neural crest cells are also discussed. PMID- 8453295 TI - New life in an old structure: the development of synaptic pathways in the spinal cord. AB - The study of the formation of synaptic circuits within the spinal cord has been hampered by the absence of accessible experimental preparations and suitable techniques. Recently, two new preparations have been described for following spinal development in vitro: slices of embryonic rat spinal cord co-cultured with sensory ganglia and myotubes, and cultures of the entire central nervous system of neonatal opossums. Optical imaging techniques have revealed spontaneous synchronous increases of Ca2+ levels in groups of spinal neurons. The widespread electrical coupling among developing spinal neurons, which may contribute to these synchronous bursts, becomes highly restricted as development proceeds. Both phenomena may play central roles in the formation of specific patterns of synaptic connections. PMID- 8453296 TI - Activity-dependent structural changes during neuronal development. AB - Activity during the early postnatal period can have a pronounced effect on the structure of neurons in the central nervous system. Recent studies in the cat visual system and in the vertebrate and invertebrate neuromuscular system, have provided new insights into the cellular and molecular features of this process. PMID- 8453297 TI - Coordinate activity in retinal and cortical development. AB - New approaches for detecting and manipulating patterns of neuronal activity have revealed diverse strategies for constructing circuits in the developing brain. Spontaneously generated patterns can provide activity-based information before the onset of sensory inputs. In addition to mechanisms based on chemical synaptic communication, coordination of activity via gap junctions can provide important cues for synchronous activity early in circuit formation. PMID- 8453298 TI - Cerato-ulmin, a toxin involved in Dutch elm disease, is a fungal hydrophobin. PMID- 8453299 TI - Mutations in the gene for the red/far-red light receptor phytochrome B alter cell elongation and physiological responses throughout Arabidopsis development. AB - Phytochromes are a family of plant photoreceptors that mediate physiological and developmental responses to changes in red and far-red light conditions. In Arabidopsis, there are genes for at least five phytochrome proteins. These photoreceptors control such responses as germination, stem elongation, flowering, gene expression, and chloroplast and leaf development. However, it is not known which red light responses are controlled by which phytochrome species, or whether the different phytochromes have overlapping functions. We report here that previously described hy3 mutants have mutations in the gene coding for phytochrome B (PhyB). These are the first mutations shown to lie in a plant photoreceptor gene. A number of tissues are abnormally elongated in the hy3(phyB) mutants, including hypocotyls, stems, petioles, and root hairs. In addition, the mutants flower earlier than the wild type, and they accumulate less chlorophyll. PhyB thus controls Arabidopsis development at numerous stages and in multiple tissues. PMID- 8453301 TI - Effects of host plant development and genetic determinants on the long-distance movement of cauliflower mosaic virus in Arabidopsis. AB - During systemic infections, viruses move long distances through the plant vascular system. The long-distance movement of cauliflower mosaic virus (CaMV) in Arabidopsis has been examined using a whole plant in situ hybridization technique called plant skeleton hybridization. CaMV moves long distance through the phloem largely following the flow of photoassimilates from source to sink leaves. During the course of plant development, sink-source relationships change and the region of the plant that CaMV can invade is progressively reduced. In Arabidopsis, we have found that conditions that influence the rate of plant development dramatically impact the long-distance movement of CaMV, because under normal conditions the rate of plant development is closely matched to the kinetics of virus movement. Ecotypes and mutants of Arabidopsis that flower early show a form of resistance to systemic CaMV infection, which we call "developmental resistance." Developmental resistance results from the fact that the rosette leaves mature early in the life of an early flowering plant and become inaccessible to virus. On the other hand, if the development of early flowering plants is retarded by suboptimal growth conditions, inoculated plants appear more susceptible to the virus and systemic infections become more widespread. We have found that other Arabidopsis ecotypes, such as Enkheim-2 (En-2), show another form of resistance to virus movement that is not based on developmental or growth conditions. The virus resistance in ecotype En-2 is largely conditioned by a dominant trait at a single locus. PMID- 8453300 TI - Regulation of pathogenesis-related protein-1a gene expression in tobacco. AB - Pathogenesis-related protein-1a (PR-1a) is a protein of unknown function that is strongly induced during the onset of systemic acquired resistance (SAR) in tobacco. The expression of PR-1a is under complex regulation that is controlled at least partially by the rate of transcription. In this study, we demonstrated that 661 bp of 5' flanking DNA was sufficient to impart tobacco mosaic virus and salicylic acid inducibility to a reporter gene. The PR-1a promoter did not respond significantly to treatments with either auxin or cytokinin. Experiments with the protein synthesis inhibitor cycloheximide indicated that protein synthesis is required for salicylate-dependent mRNA accumulation. At flowering, the PR-1a gene was expressed primarily in the mesophyll and epidermal tissues of the leaf blade and the sepals of the flower. Several artifacts, most importantly ectopic expression in pollen, were associated with the use of the beta glucuronidase reporter gene. PMID- 8453302 TI - Proteinase inhibitors in Nicotiana alata stigmas are derived from a precursor protein which is processed into five homologous inhibitors. AB - A cDNA clone, NA-PI-II, encoding a protein with partial identity to proteinase inhibitor (PI) II of potato and tomato has been isolated from a cDNA library constructed from Nicotiana alata stigma and style mRNA. The cDNA encodes a polypeptide of 397 amino acids with a putative signal peptide of 29 amino acids and six repeated domains, each with a potential reactive site. Domains 1 and 2 have chymotrypsin-specific sites and domains 3, 4, 5, and 6 have sites specific for trypsin. In situ hybridization experiments demonstrated that expression of the gene is restricted to the stigma of both immature and mature pistils. Peptides with inhibitory activity toward chymotrypsin and trypsin have been isolated from stigmas of N. alata. The N-terminal amino acid sequence obtained from this protein preparation corresponds to six regions in the cDNA clone NA-PI II. The purified PI protein preparation is likely to be composed of a mixture of up to five similar peptides of approximately 6 kD, produced in vivo by proteolytic processing of a 42-kD precursor. The PI may function to protect the reproductive tissue against potential pathogens. PMID- 8453303 TI - Molecular characterization of NADH-dependent glutamate synthase from alfalfa nodules. AB - Alfalfa NADH-dependent glutamate synthase (NADH-GOGAT), together with glutamine synthetase, plays a central role in the assimilation of symbiotically fixed nitrogen into amino acids in root nodules. Antibodies previously raised against purified NADH-GOGAT were employed to screen a cDNA library prepared using RNA isolated from nodules of 20-day-old alfalfa plants. A 7.2-kb cDNA clone was obtained that contained the entire protein coding region of NADH-GOGAT. Analysis of this cDNA and determination of the amino-terminal amino acids of the purified protein revealed that NADH-GOGAT is synthesized as a 2194-amino acid protein that includes a 101-amino acid presequence. The deduced amino acid sequence shares significant identity with maize ferredoxin-dependent GOGAT, and with both large and small subunits of Escherichia coli NADPH-GOGAT. DNA gel blot analysis of alfalfa genomic DNA suggests the presence of a single NADH-GOGAT gene or a small gene family. The expression of NADH-GOGAT mRNA, enzyme protein, and enzyme activity was developmentally regulated in root nodules. A dramatic increase in gene expression occurred coincidentally with the onset of nitrogen fixation in the bacteroid, and was absent in both ineffective plants that were nodulated with effective Rhizobium meliloti and effective plants that had been nodulated with ineffective R. meliloti strains. Maximum NADH-GOGAT expression, therefore, appears to require an effective, nitrogen-fixing symbiosis. PMID- 8453305 TI - Regulation of the low affinity IgE Fc receptor (CD23) in atopic dermatitis. AB - Alterations in the production of CD23, the IgE Fc receptor, may play a role in the etiology of atopic dermatitis and other allergic conditions. Interleukin-4 (IL-4), interferon-gamma (IFN-gamma), and interferon-alpha (IFN-alpha) are involved in coordinate regulation of CD23. IL-4 stimulates production of both CD23 and IgE. IFN-gamma also stimulates production of CD23, but suppresses production of IgE and inhibits IL-4-mediated production of CD23. IFN-alpha also suppresses these IL-4-mediated activities and, in addition, suppresses IFN-gamma mediated stimulation of CD23 production. Changes in this coordinate regulation may be involved in the development of atopic dermatitis. Expression of CD23 by Langerhans cells is stimulated by IL-4 and IFN-gamma. Further, levels of CD23 positive T cells are elevated in atopic dermatitis subjects as compared to non atopic controls, and observed skin changes appear to be related to changes in CD23-positive mononuclear cell populations. Coordinate regulation of CD23 by IFN gamma and IL-4 may also be important in other allergic conditions, parasitic infections, and a variety of disease states. PMID- 8453304 TI - OHP1: a maize basic domain/leucine zipper protein that interacts with opaque2. AB - OPAQUE2 (O2) is a regulatory gene that predominantly affects the expression of the 22-kD class of zein storage protein genes at the level of transcription. The O2 gene encodes a polypeptide belonging to the basic domain/leucine zipper (bZIP) class of transcriptional regulatory proteins. Our prior analyses have demonstrated that the O2 protein binds 22-kD zein gene promoters as a homodimer in vitro and have also suggested that O2 may bind as a heterodimer in vivo. To identify cDNAs encoding other bZIP motifs that might interact with O2, a portion encoding the bZIP motif from an O2 cDNA was used to screen an endosperm cDNA library. Sequence analysis of one isolated recombinant phage indicated the presence of a bZIP motif similar to O2. The protein product of this partial cDNA, designated OHP1, can bind the O2 target site both as a homodimer and in a heterodimeric complex with O2. Whole genome DNA gel blot analysis of maize recombinant inbreds revealed two strongly hybridizing restriction fragments, neither of which mapped close to any locus known to affect zein expression. RNA gel blot analysis revealed an approximately 1.7-kb transcript that is expressed in all organs examined except the female flower and is also expressed in endosperms homozygous for o2 and other mutations that affect zein expression (opaque7, floury2, and Defective endosperm b-30). Based on these results and previously reported data, we propose models to accommodate OHP1 in the regulation of zein gene expression by O2. PMID- 8453306 TI - T-cell chemotactic activity of cytokine LD78: a comparative study with interleukin-8, a chemotactic factor for the T-cell CD45RA+ phenotype. AB - The recombinant LD78 cytokine (rLD78) promoted migration of human peripheral T lymphocytes at concentrations from 10(-11) M to 10(-7) M, with a peak of activity at 10(-8) M. There was no difference in migration promoting activity between LD78 alpha and its variant LD78 beta. Checkerboard analysis indicated that the migration of T cells attracted by rLD78 was chemotaxis but not chemokinesis. The chemotactic activity of rLD78 was apparently ten-fold lower than that of recombinant inteleukin-8 (rIL-8) when peripheral T cells were used as the indicator cells. Subset analysis on T cells responding to rLD78 or rIL-8 indicated that rIL-8 was more chemotactic for the CD45RA+ T cell subset than the CD45RO+ subset, but did not distinguish between CD4+ and CD8+ T cell subsets. In contrast, rLD78 apparently distinguished neither between CD4+ and CD8+ T cell subsets nor between CD45RA+ and CD45RO+ subsets. PMID- 8453307 TI - Hemolysis of normal human erythrocytes by autologous serum complement. AB - Unsensitized normal human erythrocytes (E) were shown to be lysed when incubated with autologous serum in the presence of zymosan (Zy). The hemolysis proceeded slowly with a relatively constant rate for at least 24 h at 37 degrees C. It was shown that the hemolytic reaction is antibody independent and mediated by complement activation through the alternative pathway and that hemolysis is not due to the decay or inactivation of complement regulators present on the E membrane. The mechanism of the phenomenon was studied by use of several kinds of sera genetically deficient in C3, C5, C7 or C9. The reaction was found to be divided into two stages: in the first step, neither E, C5, C7 nor C9 but Zy, serum factors containing C3 and metal ions are necessary, and in the second step, neither C3 nor metal ions but E, C5, C7 and C9 are necessary. Thus, E seem to be lysed by reactive lysis induced by C5 convertase formed on Zy through alternative complement pathway activation. PMID- 8453308 TI - Interleukin-3 immunoassay in systemic lupus erythematosus patients: preliminary data. AB - Systemic lupus erythematosus (SLE) may be associated with thrombocytopenia on one hand and lymphoma on the other. Interleukin-3 (IL-3) may contribute to both conditions. IL-3 is a pleotrophic growth factor affecting the proliferation and differentiation of stem cells to committed progenitors of several hematopoietic lineages including megakaryocytes and lymphocytes. The serum level of IL-3 determined by ELISA was found to be higher in a cohort of 16 patients with SLE in comparison to health controls. The IL-3 levels were highest in 2 patients with SLE and lymphoma. Interestingly, low serum levels were detected in SLE patients with thrombocytopenia. Our preliminary results may point to the role of IL-3 in the hematopoietic changes observed in SLE. PMID- 8453309 TI - Ultrastructural morphology of human mast cell progenitors in sequential cocultures of cord blood cells and fibroblasts. AB - The ontogeny of human mast cells (HMCs) is not known, but agranular precursors committed to HMC development are present in cord blood mononuclear cells. Individual cord bloods were cocultured with murine fibroblasts and prepared for light microscopy, immunofluorescent determination of tryptase and electron microscopy after sequential times in culture. Mast cells and their progenitors were identified and quantitated during their evolution from agranular precursors in human cord blood. Each of these methods revealed similar numbers of HMC progenitors. The earliest, visible granule contents were particulate; later, scrolls superimposed on particulate materials were noted. HMC progenitors did not contain crystal granules, but fully mature HMCs present in long-term cocultures did. The developmental sequence for the evolution of the HMC lineage in vitro, made available by this new culture system, is identical to that described for the development of HMCs in vivo in sequentially examined samples of human fetal tissues. PMID- 8453310 TI - Ultrastructural similarity between bat and human mast cell secretory granules. AB - Mast cells in the tongue of the bat (Artibeus lituratus) show a well-developed Golgi area and abundant mitochondria in the granule-free perinuclear cytoplasm. Rough endoplasmic reticulum profiles, free ribosomes, mitochondria, bundles of filaments and a great number of secretory granules are found throughout the remaining cytoplasm. The granules, of various shapes and sizes, are simple containing an electron-dense, homogeneous matrix, coarse particles or cylindrical scrolls, or combinations (cylindrical scrolls with either electron-dense, homogeneous matrix or coarse particle contents). Up to now, scroll-containing granules have been considered to be a unique feature of human mast cells. PMID- 8453311 TI - Effect of butyric acid on induction of differentiation into eosinophil-like cells in human eosinophilic leukemia cells, EoL-1 cell line: possible role of granulocyte-macrophage colony-stimulating factor as an autocrine differentiating factor. AB - EoL-1 cells differentiated into mature eosinophil-like cells when incubated with butyric acid (BA). The differentiated cells possessed many granules that stained with Luxol fast blue and acquired the ability to produce leukotriene C4 and eosinophil cationic protein (ECP), and migrated toward some eosinophillotactic attractants, including PAF, IL-5, IL-3 and GM-CSF. Monoclonal antibody to GM-CSF and IL-5, especially GM-CSF, strongly decreased the ability of BA to induce differentiation, whereas antibody to IL-3 did not. Recombinant human (rh) IL-3, rhGM-CSF and recombinant mouse (rm) IL-5, by themselves, did not have the ability to induce differentiation. On the other hand, the presence of these cytokines significantly (p < 0.01) augmented BA-induced cell differentiation. Other cytokines including rhIL-1 alpha/beta, rhIL-2, rhIL-4, rhIL-6, rhIL-8, rhTNF alpha and rhIFN-gamma had no effect on differentiation. Expression of GM-CSF and GM-CSF receptor mRNA was detected in cellular RNA obtained from BA-stimulated EoL 1 cells. Moreover, about 5-10 pg/ml of GM-CSF was detected in the culture supernatant of BA-stimulated EoL-1 cells. These findings suggested that BA induced EoL-1 cell differentiation was elicited under the influence of GM-CSF endogenously produced in these cells. GM-CSF also seemed to be an autocrine differentiating factor in EoL-1 cells. PMID- 8453312 TI - HLA-DQA1 and DQB1 loci in nickel allergy patients. AB - Since an association has been reported between nickel allergy and HLA-DQA TaqI restriction fragment length polymorphism, we typed the DQA1 locus by a more precise method to confirm the association and characterize it better. Typing was extended to the DQB1 locus. The loci were typed using polymerase chain reaction and sequence-specific oligonucleotides. The DQA1 allele 0601 was slightly overrepresented among the patients, but the p value was not significant. The frequencies of DQB1 locus alleles did not differ from those of the controls. Thus we were unable to confirm any association between HLA and nickel allergy. PMID- 8453313 TI - Skin prick tests with solutions of acid anhydrides in acetone. AB - Various low molecular acid anhydrides can act as haptens and induce type I allergies. Immunoglobulin E can be detected by radioallergosorbent test (RAST) with the protein conjugates of the respective anhydrides, which are commercially available for some substances. Being almost nonsoluble in water, these species cannot be applied in a skin prick test as a water solution. We will introduce a practicable skin prick test using acetonic solutions of the haptens. 136 persons were tested with acetone for negative control and histamine for positive control. Tests were carried out with 1 and 5% acetonic solutions of phthalic anhydride (PA). The RASTs with conjugates of the PA were performed with 111 subjects who had been exposed to acid anhydrides and with 5 people who possibly had been exposed. In 14 cases, when immediate-type allergy was suspected clinically, a test was performed in addition to the respective anhydride used at the workplace. In order to avoid unspecific histamine liberation, we tested 20 volunteer control persons who had not been occupationally exposed to acid anhydrides. In the prick test performed with acetonic PA solutions, 10 of the occupationally exposed subjects, who had also had a positive result in the RAST with protein conjugates of the PA, showed positive skin reactions, and in 2 further cases, in which the skin reaction was positive, the results of the RAST were just below the limit of a positive evaluation. The skin reaction was positive in 4 cases, in spite of a negative RAST result, while the prick test was reported to be negative in 3 cases although the RAST results were considered to be positive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8453314 TI - Identification of Psilocybe cubensis spore allergens by immunoprinting. AB - Previous studies established that Psilocybe cubensis contains potent allergens, and that a significant percentage of atopic subjects were sensitized to P. cubensis spores. The objective of this study was to identify P. cubensis spore allergens using isoelectric focusing (IEF) and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) immunoprinting. Coomassie blue staining of IEF gels detected approximately 20 bands between pI 3.6 and 9.3. Immunoprints obtained with 15 P. cubensis skin test- and RAST-positive sera revealed 13 IgE-binding bands; the most reactive were at pI 5.0 (80%), 5.6 (87%), 8.7 (80%) and 9.3 (100%). SDS-PAGE resolved 27 proteins ranging from about 13 to 112 kD. SDS-PAGE immunoprints conducted with 11 skin test- and RAST-positive sera demonstrated 18 IgE-binding bands; most sera reacted to 16 (82%), 35 (100%) and 76 kD (91%) allergens. Both electrophoretic procedures demonstrated a single allergen (at pI 9.3 and 35 kD) that reacted with all sera tested. This study corroborates the allergenic significance of P. cubensis spores and identifies the allergens of greatest importance. PMID- 8453315 TI - Experimental antiasthmatic activity of RWJ 22108: a bronchoselective calcium entry blocker. AB - RWJ 22108 (N-benzyl-N-methylaminoethyl 9-(2-chloro-6-fluorophenyl)-2,3,4,5,6,9 hexahydro-7-methyl-1, 1-dioxothiacyclohepteno-[3,2-b]pyridine-8-carboxylate) is a new bronchoselective calcium entry blocker with potential use as an antiasthmatic agent. Previous studies have shown that RWJ 22108 is a potent calcium entry blocker in vitro and demonstrates tissue selectivity for airway smooth muscle over vascular smooth muscle. The current study demonstrates the in vivo activity of RWJ 22108 in several different models of airway obstruction and asthma. RWJ 22108 relaxes preconstricted airways in dogs with little effect on blood pressure when administered by aerosol. In addition, it inhibits airway obstruction induced by antigen, histamine and exogenous leukotriene D4 in guinea pigs. In a conscious sheep model of allergic asthma, aerosol RWJ 22108 inhibits antigen-induced early and late phase airway obstruction and also the cellular infiltration associated with late phase. Total leukotrienes production is decreased in the guinea pig model probably as a result of fewer inflammatory cells infiltrating the lungs as shown in the sheep model of late phase. These data suggest that RWJ 22108 may have pharmacological potential in the clinical management of asthma. PMID- 8453316 TI - Heterogeneity amongst infected children in IgE antibody repertoire to the antigens of the parasitic nematode Ascaris. AB - Plasmas from a sample of 6-year-old children chronically infected with Ascaris lumbricoides were examined by immunoblotting for IgE antibody to the pseudocoelomic fluid of adult parasites. This revealed a high degree of heterogeneity in the antibody repertoire to putative allergens of the parasite, such that none of those screened had identical recognition patterns. This heterogeneity occurred despite the fact that infection with A. lumbricoides involves both tissue-invasive and intestinal phases of the infection, which should result in close contact between the immune system and potentially allergenic components of the parasite. PMID- 8453317 TI - Methotrexate pneumonitis in bronchial asthma. AB - Methotrexate pneumonitis is one of the most unpredictable and potentially serious adverse effects associated with the use of low-dose pulse methotrexate in treating rheumatoid arthritis. However, its occurrence in treating bronchial asthma has never been reported. A patient with steroid-dependent bronchial asthma developed interstitial pneumonitis during methotrexate therapy. Dyspnea, fever and oral ulcer occurred successively during the initial 4 months of intermittent low-dose methotrexate pulse therapy. Despite severe hypoxemia and interstitial infiltration in both lung fields, the lung lesions disappeared after treatment with corticosteroid and discontinuation of methotrexate therapy. In conclusion, methotrexate pneumonitis might develop after treatment. Once pneumonitis is suspected, methotrexate should be withdrawn. PMID- 8453318 TI - Purification and N-terminal amino acid sequence of two birch pollen isoallergens (Bet v Ia and Bet Ib). PMID- 8453319 TI - Physicochemical considerations in the development and prevention of calcium oxalate urolithiasis. AB - Calcium oxalate urolithiasis is very common in western societies. In recent years significant progress has been made in identifying and quantitating physico chemical processes involved in calcium oxalate urinary stone formation. The ability of urine to inhibit the agglomeration of calcium oxalate crystals is an important protective mechanism against stone formation. The process of crystal agglomeration is modulated to a large extent by citrate and it is disturbed in patients with hypocitraturia. Dietary factors, in particular high animal protein intake appear to affect adversely the ability of urine to inhibit calcium oxalate crystal agglomeration. Effective prevention of calcium oxalate urolithiasis should aim at restoring the urine's ability to inhibit the agglomeration of crystals and more emphasis should be given to dietary measures. PMID- 8453320 TI - Immunoelectron microscopic detection of estrogen target cells in the bone marrow of estrogen-treated male Japanese quail. AB - The localization of estrogen receptors (ERs) in bone marrow cells was studied immunoelectron microscopically in the femurs of estrogen-treated male Japanese quail. The electron-dense reaction product showing ER localization was not detected in the bone marrow cells of the male quail. After 48 h of estrogen treatment, nuclear reaction product was observed in many mononuclear cells in the bone marrow. Most were located in the marrow stroma, and they were divided into undifferentiated and differentiated type cells, characterized by poorly and well developed cytoplasm, respectively. Some ER-positive cells were situated in the hematopoietic tissue and had moderately developed cytoplasm. Thus, estrogen target cells may be present in the stroma and hematopoietic tissue of bone marrow. PMID- 8453321 TI - Mineralization of dentinal collagen sheets complexed with alkaline phosphatase and integration with newly formed bone following subperiosteal implantation over osseous defects in rat calvaria. AB - We addressed the question to what extent alkaline phosphatase (ALP) can induce mineralization of a collagenous matrix implanted subperiosteally, and how the graft interacts with the underlying bone. Bovine intestinal ALP was bound to sheets of guanidine-extracted, demineralized bovine dentin by using the crosslinking agent 1-ethyl-3(3-dimethylaminopropyl)carbodiimide.HCl. The complexes (with active enzyme) and control grafts (no enzyme) were implanted over osseous defects in opposite halves of rat calvaria. After time intervals varying from 3-12 weeks, the calvaria were processed for light and electron microscopic examination and histomorphometric analysis. The ALP-containing sheets (but not their controls) rapidly accumulated mineral crystals. As the complexes mineralized, osteoblasts appeared and formed a layer of bone in direct contact with the grafted material. The results indicate that ALP induced the deposition of mineral crystals, and strongly suggest that it is this mineral component which influenced the formation of bone. PMID- 8453322 TI - The effect of ovariectomy on periosteal bone formation and bone resorption in adult rats. AB - In order to quantify the rate of bone metabolism after ovariectomy, tetracycline was injected intraperitoneally into 3-month-old female Wistar rats to label the mineralizing front and ovariectomy was performed. The rats were sacrificed 91 days later, whereupon serum calcium and phosphorus were determined. The femurs were sectioned in the upper part, photographed and the area between the tetracycline line and the outer perimeter of the bone was planimetered at a reference point. The area of periosteal bone formed was noted to be 28.3% greater than in control rats (P = 0.0002) and the area of the medullary cavity 18.8% larger (P = 0.033), indicating enhanced osteoblast and osteoclast function. The serum calcium concentration was unchanged, but a significant reduction in phosphorus was seen in the ovariectomized rats (P < 0.0001). The data suggest that the stimulated bone formation is a representative phenomenon in ovariectomized rats at least for 100 days and bone resorption remains elevated in the course of processes possibly leading to osteoporosis. PMID- 8453323 TI - Bone-resorbing activity of different periprosthetic tissues in aseptic loosening of total hip arthroplasty. AB - Using bone organ culture techniques, we studied the production of bone-resorption stimulating factors by the different tissues surrounding loosened total hip arthroplasties. Revision arthroplasties were performed in 13 patients. Various periprosthetic tissues were obtained from these patients. Culture media conditioned by the newly formed capsules contained higher bone-resorption activity when compared to the resorptive activity found in media conditioned by bone-cement membranes. Addition of indomethacin or structurally unrelated non steroidal anti-inflammatory drugs, or corticosteroids, to bone-cement membrane cultures altered the process of bone resorption in the vicinity of cemented joint implants suggesting that both prostaglandin and other mediators may be involved in the mechanism by which bone-resorbing osteoclasts are stimulated. Our observations indicate that, in the sequence of events that leads to loosening of implants, mediators released from the joint capsules may be more important than those produced by the bone-cement membranes. PMID- 8453324 TI - Differences in the time course of the effects of oophorectomy in women on parameters of bone metabolism and interleukin-1 levels in the circulation. AB - Interleukin-1 is a cytokine with bone-resorbing activity which is claimed to play a role in the pathogenesis of osteoporosis and of post-oophorectomy bone loss. We measured plasma levels of interleukin-1 (IL-1) in 16 women who underwent hysterectomy and bilateral oophorectomy and in 12 women with hysterectomy alone before surgery and 7, 15, 30, 45 and 60 days after surgery. Only oophorectomized patients showed a significant increase of circulating interleukin-1 levels. This increase was significant only 30 days after surgery, whereas a rise at 7 days (P < 0.001) was observed for serum calcium and hydroxyproline/creatinine and calcium/creatinine ratios. These data do not indicate a definite role of IL-1 in promoting bone resorption in estrogen-deficient women in vivo. PMID- 8453325 TI - Calcium citrate without aluminum antacids does not cause aluminum retention in patients with functioning kidneys. AB - It has been suggested that calcium citrate might enhance aluminum absorption from food, posing a threat of aluminum toxicity even in patients with normal renal function. We therefore measured serum and urinary aluminum before and following calcium citrate therapy in patients with moderate renal failure and in normal subjects maintained on constant metabolic diets with known aluminum content (967 1034 mumol/day, or 26.1-27.9 mg/day, in patients and either 834 or 1579 mumol/day, or 22.5 and 42.6 mg/day, in normal subjects). Seven patients with moderate renal failure (endogenous creatinine clearance of 43 ml/min) took 50 mmol (2 g) calcium/day as effervescent calcium citrate with meals for 17 days. Eight normal women received 25 mmol (1 g) calcium/day as tricalcium dicitrate tablets with meals for 7 days. In patients with moderate renal failure, serum and urinary aluminum were normal before treatment at 489 +/- 293 SD nmol/l (13.2 +/- 7.9 micrograms/l) and 767 +/- 497 nmol/day (20.7 +/- 13.4 micrograms/day), respectively. They remained within normal limits and did not change significantly during calcium citrate treatment (400 +/- 148 nmol/l and 600 +/- 441 nmol/day, respectively). Similarly, no significant change in serum and urinary aluminum was detected in normal women during calcium citrate administration (271 +/- 59 vs 293 +/- 85 nmol/l and 515 +/- 138 vs 615 +/- 170 nmol/day, respectively). In addition, skeletal bone aluminum content did not change significantly in 14 osteoporotic patients (endogenous creatinine clearance of 68.5 ml/min) treated for 24 months with calcium citrate, 10 mmol calcium twice/day separately from meals (29.3 +/- 13.9 ng/mg ash bone to 27.9 +/0- 10.4, P = 0.727). In them, histomorphometric examination did not show any evidence of mineralization defect. Thus, calcium citrate given alone without aluminum-containing drugs does not pose a risk of aluminum toxicity in subjects with normal or functioning kidneys, when it is administered on an empty stomach at a recommended dose of 20 mmol calcium/day. PMID- 8453326 TI - Seasonal variations of 25 hydroxyvitamin D and parathyroid hormone in Ushuaia (Argentina), the southernmost city of the world. AB - Serum levels of calcium, phosphorus, alkaline phosphatase, 250HD, 1.25(OH)2D and PTH were studied in a group of 42 children aged 8.5 +/- 1.8 years (X +/- SD) from the city of Ushuaia (latitude 55 degrees S), at both the end of the winter and the end of summer. Calcium, phosphorus, alkaline phosphatase and 1.25(OH)2D serum levels were not different in summer and winter. The levels of serum 25OHD were significantly higher in summer (18.4 +/- 7.3 ng/ml) than in winter (9.8 +/- 3.8 ng/ml P < 0.001). The levels of 25OHD in children with fair or dark skin were similar in winter but were significantly higher in children with fair skin in summer (20.0 +/- 7.2 ng/l vs 15.3 +/- 5.1 ng/ml (P < 0.05). Serum levels of PTH were higher in winter (58.2 +/- 30.5 pg/ml) than in summer (47.9 +/- 28.3 pg/ml) (P < 0.03). The results demonstrate the existence of a population with low serum levels of 25OHD in winter. The higher levels of PTH in winter when serum 25OHD levels are lower could be the cause of the lack of seasonal variation in serum calcium and 1.25(OH)2D levels. Further studies are needed to establish whether these changes besides increasing the incidence of rickets, could also affect the mineral density of the skeleton in the population of this vitamin-D-deficient area. PMID- 8453327 TI - Trabecular bone mineral density in primary hyperparathyroidism: relationship to clinical presentation and biomarkers of skeletal turnover. AB - This study was carried out in order to investigate the entity of trabecular bone involvement in 62 patients with primary hyperparathyroidism (PHPT). Bone mineral density (BMD) was measured in all patients at the ultradistal radius (UDR) of the non-dominant arm by a dual photon densitometer and also at the lumbar spine (L) in 40 of the patients by means of quantitative dual energy radiography. Mean Z score values of UDR-BMD (-2.4 +/- 0.4) and L-BMD (-3.5 +/- 0.2) in patients with the skeletal variety of the disease (n = 6) were significantly reduced in respect to values of both asymptomatic (n = 31) and kidney stone patients (n = 25). As far as the comparison between the two sites of trabecular bone mass measurement in each hyperparathyroid subgroup of patients was concerned, a significant difference (P < 0.05) was found in patients with skeletal manifestations of the disease. Either serum total alkaline phosphatase activity, or osteocalcin and the 24-h hydroxyproline/creatinine ratio were significantly inversely related to the entity of bone mass evaluated at these two sites. Z score changes following surgery in 14 patients showed a positive trend in 13 of them at L compared to 7 out of 14 at UDR (P < 0.036 by chi square analysis). There was a very good inverse correlation between basal Z score values and the changes following surgery at the L (r = -0.851; P < 0.001) but not at the UDR. Our results demonstrate firstly that, in PHPT skeletal sites with almost similar composition of trabecular bone are differently involved in patients with more severe skeletal damage and that different skeletal sites may be divergently affected by the cessation of parathyroid gland hyperfunction. PMID- 8453328 TI - High intensity activities in young women: site specific bone mass effects among female figure skaters. AB - We compared young female figure skaters, aged 10-23, with non-athletic control subjects to ascertain whether there were differences in skeletal densities at various sites. We also compared other characteristics of body size, including height, weight and percent body fat. Although the skaters were thinner and significantly more likely to have oligo- or amenorrhea, they had similar skeletal densities at upper body sites (spine, arms, ribs) and significantly greater densities in the pelvis and legs. These differences were not evident until the mid-teens, however, suggesting that there is little likelihood of selection bias as the cause of the observed differences. PMID- 8453329 TI - Sex hormones and bone mineral density in elderly men. AB - The aim of this study was to determine the relationships between sex hormones and bone mineral density (BMD) in older men. Community-dwelling men (n = 134, mean age (SD) 69.5 (3.1) years) were recruited from two general practices in Cambridge, UK. Plasma total testosterone and sex hormone binding globulin (SHBG) were assayed and a free androgen index (FAI) was derived as the ratio of total testosterone to SHBG (x 100). Spine and hip BMD were measured by dual energy x ray absorptiometry using the Hologic QDR-1000. After adjusting for age and body mass index (BMI), the FAI correlated with femoral neck (r = 0.20, P = 0 0.03), intertrochanteric, trochanteric and Ward's Triangle BMD (r = 0.22, P = 0.01). Analysis of variance, with adjustment for age and BMI, showed a progressive upward trend of hip BMD with increasing quartiles of FAI. The findings suggest that free testosterone plays a role in determining bone mineral density in older men. PMID- 8453330 TI - The association of lifetime weight and weight control patterns with bone mineral density in an adult community. AB - We examined the association of lifetime weight and weight change to bone mineral density (BMD) at four skeletal sites, the radial shaft, the ultradistal wrist, the total hip and lumbar spine, in a community-based population of 1043 older white men and women. In those currently overweight (body mass indices (BMI) > 26), the age-adjusted mean BMD at all sites was significantly higher than in those with BMI less than 26. Lifetime maximum BMI was also positively and significantly associated with a higher age-adjusted BMD at all sites except the ultradistal wrist in men. Weight gain or fluctuation of 10 lbs or more between the ages of 40 and 60 was associated with significantly higher age-adjusted mean BMD at all sites compared to weight loss or no weight change in both men and women. Weight at age 18 was unassociated with BMD but weight gain after age 18 was associated with significantly higher age-adjusted mean BMD at all sites. Conversely, dieting, weight loss or a lifetime maximum BMI of less than 24 were all associated with markedly lower BMD at all sites in both sexes. Weight patterns were closely correlated with current BMI; most of these trends persisted but were no longer statistically significant after controlling for current weight. PMID- 8453331 TI - Maclura pomifera agglutinin-binding glycoconjugates on converted apatite from synthetic octacalcium phosphate implanted into subperiosteal region of mouse calvaria. AB - We have previously shown that the mineral in granules of synthetic octacalcium phosphate (OCP) implanted subperiosteally in mouse calvariae was converted to apatitic crystals and that the OCP implantation stimulated bone formation. The matrix components accumulated on the converted apatite were very similar to those of bone nodules (starting locus of calcification) in intramembranous osteogenesis. In the present study, the nature of the matrices accumulated on OCP implants in calvariae was compared with that of the matrices accumulated in abdominal subcutaneous implants. The comparison was facilitated by the use of Maclura pomifera agglutinin (MPA) lectin which is known to have a high affinity for the primary intramembranous bone matrix. Micro-beam x-ray diffraction indicated conversion of the implanted OCP to apatitic crystals in situ, both in subperiosteal and subcutaneous sites, after 10 days. Additional bone formation was detected on the converted apatite after 13 days in subperiosteal implantation, whereas bone was not formed in the subcutaneous implantation. MPA reaction was strongly manifested after 10 days in matrices accumulated on the converted apatite in both subperiosteal and subcutaneous implantations. Biochemical data showed that intensely and weakly MPA-blotted molecules (53.0 and 152.6 kDa, respectively) were in all the mouse sera, in the guanidine HCl-EDTA extracts of mouse calvarial bone and in the extracts of the implanted OCP in both subperiosteal and subcutaneous sites. These findings indicated that the glycoconjugates accumulated on the converted apatite from OCP were similar to the glycoconjugates in the serum in terms of reactivity with MPA and molecular weights. Furthermore, the results suggest that MPA-binding glycoconjugates which had accumulated on the converted apatite may be a requisite for the differentiation of mesenchymal cells into osteoblasts in periosteum but not in subcutaneous sites. PMID- 8453332 TI - Induction of bone formation in rat tail vertebrae by mechanical loading. AB - We have developed an experimental model in which pins, inserted into the seventh and ninth caudal vertebrae of 13-week-old rats, are used to load the eighth caudal vertebra in compression. Four groups of animals were used in the study: unpinned; animals with pins inserted, but non-loaded; animals loaded once, for 360 cycles at 0.5 Hz; and animals subjected to daily loading for 36 cycles at 0.5 Hz. Pins were immobilised by clamps when not undergoing loading. The animals were killed 9 days after pinning, and the eighth caudal vertebra was subjected to histomorphometric and histodynamic analysis. We found that vertebrae subjected to 36 daily loading cycles showed a 30-fold increase in bone formation compared to non-loaded controls. A single loading regime of 360 cycles was sufficient to increase bone formation 4-fold. Bone formation on trabecular surfaces was of lamellar rather than woven bone and was accompanied by a decrease in indices of bone resorption. Loaded vertebrae also showed substantial periosteal woven bone formation, although a minor degree of periosteal woven bone formation was also seen in one non-loaded pinned control vertebra. Our results suggest that in the rat, as in avian species, short loading regimes are capable of inducing bone formation. The model may assist an analysis of the interactions between bone resorption, bone formation and mechanical stimuli, and may enable identification of the molecular signals that mediate induction of lamellar bone formation on trabecular surfaces. PMID- 8453333 TI - Gallium nitrate inhibits alkaline phosphatase activity in a differentiating mesenchymal cell culture. AB - The effect of gallium nitrate on alkaline phosphatase activity in a differentiating chick limb-bud mesenchymal cell culture was monitored in order to gain insight into the observation that rachitic rats treated with gallium nitrate failed to show the expected increase in serum alkaline phosphatase activity. Cultures maintained in media containing 15 microM gallium nitrate showed drastically decreased alkaline phosphatase activities in the absence of significant alterations in total protein synthesis and DNA content. However, addition of 15 microM gallium nitrate to cultures 18 h before assay for alkaline phosphatase activity had little effect. At the light microscopic and electron microscopic level, gallium-treated cultures differed morphologically from gallium free cultures: with gallium present, there were fewer hypertrophic chondrocytes and cartilage nodules were flatter and further apart. Because of altered morphology, staining with an antibody against chick cartilage alkaline phosphatase appeared less extensive; however, all nodules stained equivalently relative to gallium-free controls. Histochemical staining for alkaline phosphatase activity was negative in gallium-treated cultures, demonstrating that the alkaline phosphatase protein present was not active. The defective alkaline phosphatase activity in cultures maintained in the presence of gallium was also evidenced when cultures were supplemented with the alkaline phosphatase substrate, beta-glycerophosphate (beta GP). The data presented suggest that gallium inhibits alkaline phosphatase activity in this culture system and that gallium causes alterations in the differentiation of mesenchymal cells into hypertrophic chondrocytes. PMID- 8453334 TI - The interaction between policy and research in the implementation of server training. AB - This paper describes the relationship between research and policy in the development of server training policy in Ontario. With the emergence of civil liability for the conduct of intoxicated patrons, there has been a growing movement toward the training of managers and servers in licensed establishment in the responsible service of alcohol. As part of a major government reform of alcohol regulations which has led to a new Liquor Licence Act, all persons who serve alcohol in licensed establishments in Ontario will be required to attend a server training course. The process leading to new alcohol regulations in Ontario is summarized with particular attention to the implementation of mandatory server training. The paper concludes with a discussion of the role of research in policy development. It is argued that the role of research in policy making is limited by an inherent conflict between the nature of scientific enquiry and the exigencies of policy development. PMID- 8453335 TI - The policy-research interface: an insider's view. AB - This paper is a summary of some illuminating comments made by the author when invited to discuss some of the above papers in the area of liquor licensing and availability. Prior to his appointment as the Director and Government Printer of State Print in South Australia, the author had been the first Director of Liquor Licensing in Western Australia. In that capacity he was responsible for undertaking a major review of the Liquor Act in Western Australia and in implementing a new administrative structure. He was subsequently appointed as the Chief Executive Officer of the Western Australian Totalisator Agency Board (which is responsible for off-course betting on horse and greyhound racing) before returning to South Australia. The author's experience of reviewing liquor licensing legislation in both South Australia and Western Australia, and his administration of a licensing authority provides him, in the Editors' view, with unique insights into the working of governments and the formulation of policy in this area. His paper is presented here in the form in which it was given at the conference. PMID- 8453336 TI - The interaction between research and policy--alcohol and general practice in the United Kingdom. AB - Research evidence is considered for the effectiveness of screening for alcohol consumption in general practice and for the effectiveness of brief interventions in general practice. Evidence is then considered for the effectiveness of dissemination of brief interventions throughout general practice. The example of dissemination of smoking interventions is used as similar data is not yet available for alcohol. The structure of the UK contract for general practice is discussed and its relationship to research findings considered. Finally, future directions for both research and policy are highlighted. PMID- 8453337 TI - Failures in alcohol policy: lessons from Russia, Kenya, Truk and history. AB - The paper draws upon the recent developments of alcohol policy in the ex-Soviet Union and in Africa, especially Kenya. According to the standard criteria of success, both are to be regarded as total or near-total failures. The examination of these cases will, consequently, reveal some of the factors that are essential prerequisites for carrying out successful alcohol policies. It will lead to considerations concerning the approaches and problems of alcohol research; to a discussion about the marginalization of alcohol and drinking in our Western societies; to another look at the tasks of alcohol policies (based also on experiences in Truk, Federated States of Micronesia); and, finally, to a rather modest view about the role of alcohol policy in general. PMID- 8453338 TI - Lessons to be learnt from Poland's attempt at moderating its consumption of alcohol. AB - This paper analyses the interplay between alcohol policy and research in Poland during the last two decades. It was a period of profound political and economic changes that strongly influenced the alcohol scene. In the 1970s alcohol was treated as a secret issue. Despite a rapid growth of alcohol consumption neither the authorities nor media expressed any concern about the growing wave of related problems. Funding allocated to research was very low and only a few devoted individuals continued their studies, albeit on a reduced scale. The beginning of the 1980s saw a sudden politicization of the alcohol issue. The government was blamed for pushing alcohol. In response to this challenge, alcohol controls were tightened. A huge programme of alcohol research was initiated to accumulate knowledge and evidence for further alcohol policy, as well as to symbolize a high priority of the alcohol issue. In following years, however, the political significance of alcohol decreased. The system established for its control was eroded, and finally collapsed in the late 1980s and early 1990s. The huge research evidence that was accumulated during the 1980s is not being applied to alcohol policy, which itself has virtually ceased to exist. PMID- 8453339 TI - From large projects to case consultation--interaction of alcohol research and policy in Finland. AB - The interaction of Finnish social alcohol research and alcohol policy will be discussed in this paper. We will examine the history of alcohol research, focusing on the extent that problems related to alcohol policy have been covered in research. We also deliberate upon such questions as to what extent changes in alcohol policy can be linked to the findings of research. Researchers began their work in the 1950s, hoping to find a solution to the problems met in alcohol policy. In the 1960s the era of alcohol policy-centred projects was followed by an era which aimed to increase the factual knowledge of alcohol not necessarily tied to alcohol policy questions. After 1969 alcohol policy questions gained renewed interest. Alcohol research has not directly caused many new measures, but it has influenced the public and private discussion about alcohol policy. Producing results and research reports has been an important way to affect both public discussions and policy making. However, participating in the decision making processes in its different stages has been an even more crucial way to affect alcohol policy. Particularly in the 1970s, the ideas and views presented in studies had fairly immediate and direct repercussions on both alcohol policy and practical measures. PMID- 8453340 TI - The formulation of Australia's National Health Policy on Alcohol. AB - The formulation of a health policy in relation to alcohol is described by the Chairman of the Committee responsible for its drafting in the context of Australia's pursuance of a National Campaign Against Drug Abuse. The fate of particular proposals included in the draft document, but excluded from the final endorsed policy, is discussed in relation to the activities of the alcohol industry and, in particular, the intervention of the Minister for Health in South Australia, Australia's premium wine growing region. Inferences are drawn about the negotiation of public health policy in this area, the role of research and the need to demonstrate widespread public support for the recommendations of such research. PMID- 8453341 TI - Random breath testing in Australia: getting it to work according to specifications. AB - After reading the deterrence literature, particularly the work of H. Laurence Ross, I concluded in the late 1970's that many road accidents could be prevented through the wholehearted implementation of random breath testing (RBT). RBT is a system of drink-drive law enforcement which aims to increase the perceived likelihood of apprehension through the use of mass breath testing techniques at roadblocks which are highly visible, are unpredictable in their locations and give the impression of ubiquity. As the result of public pressure, RBT was introduced in NSW in December 1982, with spectacular results. The law was intensively enforced and extensively advertised, partly due to the advocacy of researchers such as myself, but also because ther was an acute political need for instant results. Since RBT is a difficult enforcement technique for police to sustain in effective form, researchers must strive to improve their understanding of what works, and remain in close contact with police, policy makers and politicians. Although this process is costly in terms of time and, possibly, academic 'pay-off', it is essential if the fragile understanding of deterrence principles amongst these groups is not to lead to superficially attractive, but probably ineffective techniques such as low visibility mobile RBT. PMID- 8453342 TI - Interaction of public policy advocacy and research in the passage of New Zealand's Smoke-free Environments Act 1990. AB - This paper examines the public policy campaign that led up to the passage of New Zealand's Smoke-free Environment Act 1990, arguably the toughest tobacco control legislation in the world, focusing on the critical interaction between advocacy and research. The paper argues that had it not been for the Toxic Substances Board Report and the publicity it received, it is doubtful that the Smoke-free Environments Act would have been enacted. The tobacco industry catch cry that ad bans don't work, largely fell on deaf ears because of the Toxic Substances Board Report's findings, and the public health advocate's ability to refer to an authoritative Department of Health document. PMID- 8453343 TI - Guarding the guardians: influencing the regulation of alcohol promotions in Australia. AB - Alcoholic beverage advertising in Australia is allowed provided it conforms with a Code of Conduct approved by the Media Council of Australia (a collective of media proprietors). This system, known as self-regulation, has come under increasing critical scrutiny. It is argued from a systemic perspective that research has been one factor that has led to this increased scrutiny of alcoholic beverage advertising. Important other factors include the advent of the Australian National Campaign against Drug Abuse (which crucially included alcohol on its agenda), some erosion of the alcoholic beverage producers political status, declining per capita consumption, and an increase in media reporting on alcohol and drug issues. By examination of five research reports recently released on alcohol advertising it is argued that, in order to influence policy makers in an area where there is substantial opposition to change, research must be deftly marketed, contain information of political relevance, such as opinion poll material, and be used as a lobbying tool. The role of researchers in this process is considered. PMID- 8453344 TI - Helping research and policy meet. PMID- 8453345 TI - Influencing the labelling of alcoholic beverage containers: informing the public. AB - In 1990, a small research project costing about Aus. $4500 conducted in a Perth shopping centre directly influenced the development of a national policy within 4 months of its completion. The policy in question is a recommendation by Australia's Ministerial Council on Drug Strategy that all alcoholic beverage containers should carry labels indicating the number of 'standard drinks' they contain. The purpose of this paper is to describe the events leading up to so unusual an event with a view to discerning what factors may have been critical for its occurrence. The paper attempts to analyse the nature of the interactions between the research team and the policy makers. It is argued that the critical factors included there being a favourable policy climate created by the National Campaign Against Drug Abuse, the support of influential public servants and, in turn, politicians, the consultative process which lead to the study's design and the manner in which the findings were disseminated. PMID- 8453346 TI - The relevance of research to policy formulation: an Australian perspective. AB - This paper puts the role of research into perspective in the policy-making context. It points out that there are differing 'policy' goals of government and the use of research might be vital for one element, e.g. health policy, but of lesser significance in, say, international policy. The paper then goes on to describe case studies of where research has had a major impact on government decision making in Australia in the past 2 years, notably in the area of proposed changes to the marketing and sale of alcoholic beverages. PMID- 8453347 TI - Changes in access to and availability of alcohol in the United States: research and policy implications. AB - Recent changes in alcohol availability and access in the United States are reviewed and the role public policy research played in such changes are discussed. The paper finds that there are two concurrent trends, i.e. increased alcohol availability through changes in wine and spirits structural availability, lower prices and increased outlet densities, and decreased availability and access through higher minimum drinking ages, server intervention and training, server liability, low- and no-alcohol beverages, and warning labels on alcohol containers. This paper discusses these trends and the implications for policy development to which research is an input. PMID- 8453348 TI - Research affects public policy: the case of the legal drinking age in the United States. AB - After receiving little attention from 1940 to 1970, minimum-age laws were a focus of debate and policy change in the United States from 1970 to 1985. In the 1970s, 29 states lowered the legal age, and in the late 1970s and early 1980s, all states with an age below 21 raised the legal age to 21 for all types of alcoholic beverages. Research on the effects of such policy changes were a central component in the political debates on minimum-age laws. The process by which research results influenced public policy deliberations is discussed. Characteristics that facilitated research results being taken into account in the policy debates included: (1) research of high interval validity that withstood challenge, (2) dissemination of the research results beyond networks of scientists, and (3) participation of bridging individuals who learned of the research results, and condensed and communicated key findings to policy-makers. PMID- 8453349 TI - Community-based research initiatives in prevention. AB - An overview of community-based action research projects is presented focusing on the community/research agenda interaction, the difficulties and rewards of this approach, and the unique opportunities of these projects. The potential for policy development as a result of these initiatives has not been fully explored, and some suggestions for the implementation of policies based on the results of action research projects are made. The policy implication of several specific interventions are discussed, along with the limitations and benefits of policy components within a project, rather than as spin-offs. The paper concludes with suggestions for planning community action projects to enhance the policy formulation aspect of these projects. PMID- 8453350 TI - The negotiation of New Zealand alcohol policy in a decade of stabilized consumption and political change: the role of research. AB - Significant changes in the key alcohol policy areas of availability, advertising and taxation have taken place in New Zealand from 1985 to 1991. These changes are described in the context of the social climate which was one of extreme fiscal crisis and an unprecedented swing to the right. The very limited role played by public health research in the process of policy development is viewed in part as a consequence of this social climate. The political changes affected the strength and extent of the public health voices in the debate and the reception they received. In each of the policy areas in which change occurred, the policy-keeper was other than a public health agency and the utilization of research by public health advocates was, therefore, in response to already articulated positions. The dissemination of research relied too heavily on lengthy written submissions, and too little on media advocacy and interpersonal contact. There was also a lack of directly relevant local research to inform the policy debate. The case study illustrates the constraints on researchers' in the policy development process, but suggests that such involvement is important for the public's health. PMID- 8453351 TI - The introduction of dram shop legislation in the United States and the advent of server training. AB - This paper discusses the relationship of research to policy in the matter of dram shop liability and server training in the USA. The discussion is made difficult by the apparent lack of any such relationship. While research in the area has only just been published, dram shop liability in the USA actually dates to the nineteenth century, with its current form shaped by the repeal of prohibition in 1933. Because liability law and liability insurance vary from state to state, current movements for reform and server training arise somewhat spontaneously in different localities and with different emphases. Research constitutes only a minor influence among several others more salient to the political process of policy formation. The advent of mandatory server training in the state of Oregon is used to illustrate the somewhat capricious nature of progress in responsible beverage service. PMID- 8453352 TI - Global policies and the peoples' health. PMID- 8453353 TI - Human immunodeficiency virus-1 infection among patients with sexually transmitted diseases in Bombay. AB - BACKGROUND: Patients with sexually transmitted diseases form a particularly vulnerable group for infection with the human immunodeficiency virus (HIV-1), and serological surveillance is a sensitive tool for assessing the prevalence of this disease. METHODS: We carried out a serological survey for the detection of antibody to HIV-1 among persons belonging to various high-risk groups in Bombay from 1987 to 1989. Among these were 599 patients with various sexually transmitted diseases. RESULTS: Thirty-nine patients (5.2%) were found to be HIV-1 antibody seropositive by the ELISA and Western blot tests. An increase in HIV-1 antibody seropositivity among both the male and female patients with sexually transmitted diseases was detected from 1987 to 1989 and seropositivity was maximally associated with condylomata acuminata, genital herpes and chancroid. CONCLUSION: HIV-1 is established in this sentinel population and needs to be controlled vigorously. PMID- 8453354 TI - Assessment of transcervical chorion villus aspiration biopsy in early pregnancy. AB - BACKGROUND: Chorionic villus sampling for prenatal diagnosis is a relatively new technique and variable success rates have been reported by different authors depending on the methods and instruments used. We describe our experience with chorionic villus sampling in Bombay. METHODS: The procedure was attempted on 62 women before termination of their pregnancy via the transcervical route, under constant real-time ultrasound guidance. A metallic cannula was negotiated through the cervix into the uterine cavity to reach the chorionic frondosum and chorionic villi were aspirated by creating a negative pressure in the syringe attached to the cannula. The villus tissue was checked under a dissecting microscope. We calculated the success rate for obtaining a sample depending on the site of the chorionic frondosum, the physique of the mother, the position of the uterus and the size of the cannula. RESULTS: Villus tissue was aspirated in 47 of the 62 cases. The success rates of sampling at the first and second attempts were 48% and 27% respectively. The factors which were associated with a higher success rate were when the chorionic frondosum was situated posteriorly rather than anteriorly (61% v. 48%; p < 0.01), when the patient was thin rather than fat (58% v. 25%; p < 0.001), when the uterus was anteverted rather than retroverted (53% v. 41%). The commonest complication was bleeding which occurred in 15% of patients. CONCLUSION: Transcervical chorionic villus sampling is associated with a high success rate except in fat women with a retroverted uterus and in those with the chorionic frondosum situated in the fundus. PMID- 8453355 TI - Seasonal trends in the occurrence of eclampsia. AB - BACKGROUND: The occurrence of eclampsia may be related to season and altitude. METHODS: We studied the influence of environmental factors such as range of temperature and relative humidity on the occurrence of eclampsia by collecting data on consecutive cases of eclampsia admitted to the Government Maternity Hospital, Hyderabad, from September 1987 to August 1988. The mean range of temperature and relative humidity were calculated for each month. The data on eclampsia and adverse outcome in terms of still-births were analysed in relation to variations in temperature and humidity. RESULTS: The results support the speculated relationship between increasing humidity and a lower temperature range and the increased incidence of eclampsia. Still-births due to eclampsia also showed a positive correlation with relative humidity. CONCLUSION: A better understanding of the relationship of weather to eclampsia may provide further insight into the poorly understood pathophysiology of the disease. PMID- 8453356 TI - Interleukin-2 in autologous bone marrow transplantation. AB - Interleukin-2 results in the generation of lymphokine activated killer cells which exhibit a potent effect against a wide variety of tumours. Consequently, interleukin-2 therapy has been used to induce a graft versus tumour effect following autologous bone marrow transplantation. Preclinical studies have shown that this results in successful engraftment, and an enhanced reconstitution of the immune system. PMID- 8453357 TI - Corticosteroid inhalers and pulmonary tuberculosis. PMID- 8453358 TI - Health and poverty--a tale of two cities. PMID- 8453359 TI - Ear canal cholesteatomas--do they exist? PMID- 8453360 TI - Intraocular lens implantation. PMID- 8453361 TI - The medical management of upper gastrointestinal bleeding. PMID- 8453362 TI - Relieving biliary obstruction. PMID- 8453363 TI - Eminent Indians in medicine. B. Mukopadhaya. PMID- 8453364 TI - Sustainability beyond starvation. PMID- 8453365 TI - Another viewpoint. PMID- 8453366 TI - Fraud in biomedical science. PMID- 8453367 TI - Fraud in biomedical science. PMID- 8453368 TI - Indian medical journals. PMID- 8453369 TI - Survival in multiple myeloma in Kerala. AB - BACKGROUND: The reported incidence of multiple myeloma in India ranges from 0.5 to 1.2 per 100,000 but there have been few studies on the effect of treatment of this condition. We, therefore, analysed the clinical profile of patients in Kerala with myeloma, the treatment given and the factors affecting survival. METHODS: Case records of 142 patients with multiple myeloma treated at the Regional Cancer Centre, Trivandrum, between 1984 and 1989 were reviewed and abstracted. Chemotherapy (using melphalan and prednisolone) and radiotherapy were the treatment modalities. Survival analysis was done using the Kaplan-Meier estimates and multivariate analysis of factors affecting survival was performed using Cox's proportional hazards regression model. RESULTS: The mean age of the patients was 61 years and 90 were males. Bone pain and pallor were the most common presenting symptoms and the median survival was 30 months. A combination of melphalan and prednisolone was found to be well tolerated and achieved a survival rate of 62% at 5 years. Hemibody irradiation was beneficial in a small group of patients. On a multivariate analysis, Bence-Jones proteinuria, melphalan and prednisolone combination chemotherapy and response to treatment at 6 months were the most significant factors affecting survival. Socioeconomic status did not seem to influence survival. CONCLUSIONS: Melphalan and prednisolone chemotherapy achieves prolonged survival in myeloma. Radiotherapy can relieve symptoms and in a small group of patients hemibody irradiation can achieve prolonged remission. Further studies are required to identify the subgroups in which certain treatments are most effective in improving survival. PMID- 8453370 TI - Structural analysis based on state-space modeling. AB - A new method has been developed to compute the probability that each amino acid in a protein sequence is in a particular secondary structural element. Each of these probabilities is computed using the entire sequence and a set of predefined structural class models. This set of structural classes is patterned after Jane Richardson's taxonomy for the domains of globular proteins. For each structural class considered, a mathematical model is constructed to represent constraints on the pattern of secondary structural elements characteristic of that class. These are stochastic models having discrete state spaces (referred to as hidden Markov models by researchers in signal processing and automatic speech recognition). Each model is a mathematical generator of amino acid sequences; the sequence under consideration is modeled as having been generated by one model in the set of candidates. The probability that each model generated the given sequence is computed using a filtering algorithm. The protein is then classified as belonging to the structural class having the most probable model. The secondary structure of the sequence is then analyzed using a "smoothing" algorithm that is optimal for that structural class model. For each residue position in the sequence, the smoother computes the probability that the residue is contained within each of the defined secondary structural elements of the model. This method has two important advantages: (1) the probability of each residue being in each of the modeled secondary structural elements is computed using the totality of the amino acid sequence, and (2) these probabilities are consistent with prior knowledge of realizable domain folds as encoded in each model. As an example of the method's utility, we present its application to flavodoxin, a prototypical alpha/beta protein having a central beta-sheet, and to thioredoxin, which belongs to a similar structural class but shares no significant sequence similarity. PMID- 8453371 TI - Reconstruction of protein conformations from estimated positions of the C alpha coordinates. AB - Protein C alpha coordinates are used to accurately reconstruct complete protein backbones and side-chain directions. This work employs potentials of mean force to align semirigid peptide groups around the axes that connect successive C alpha atoms. The algorithm works well for all residue types and secondary structure classes and is stable for imprecise C alpha coordinates. Tests on known protein structures show that root mean square errors in predicted main-chain and C beta coordinates are usually less than 0.3 A. These results are significantly more accurate than can be obtained from competing approaches, such as modeling of backbone conformations from structurally homologous fragments. PMID- 8453372 TI - Spontaneous degradation of polypeptides at aspartyl and asparaginyl residues: effects of the solvent dielectric. AB - We have investigated the spontaneous degradation of aspartate and asparagine residues via succinimide intermediates in model peptides in organic co-solvents. We find that the rate of deamidation at asparagine residues is markedly reduced in solvents of low dielectric strength. Theoretical considerations suggest that this decrease in rate is due to the destabilization of the deprotonated peptide bond nitrogen anion that is the postulated attacking species in succinimide formation. This result suggests that asparagine residues in regions with low dielectric constants, such as the interior of a protein or in a membrane bilayer, are protected from this type of degradation reaction. On the other hand, we found little or no effect on the rate of succinimide-mediated isomerization of aspartate residues when subjected to the same changes in dielectric constant. In this case, the destabilization of the attacking peptide bond nitrogen anion may be balanced by increased protonation of the aspartyl side chain carboxyl group, a reaction that results in a superior leaving group. Consequently, any protein structure or conformation that would increase the protonation of an aspartate side chain carboxyl group can be expected to render that residue more labile. These results may help explain why particular aspartate residues have been found to degrade in proteins at rates comparable to those of asparagine residues, even though aspartyl-containing peptides degrade more slowly than corresponding asparaginyl-containing peptides in aqueous solutions. PMID- 8453373 TI - Ribonuclease S-peptide as a carrier in fusion proteins. AB - S-peptide (residues 1-20) and S-protein (residues 21-124) are the enzymatically inactive products of the limited digestion of ribonuclease A by subtilisin. S peptide binds S-protein with high affinity to form ribonuclease S, which has full enzymatic activity. Recombinant DNA technology was used to produce a fusion protein having three parts: carrier, spacer, and target. The two carriers used were the first 15 residues of S-peptide (S15) and a mutant S15 in which Asp 14 had been changed to Asn (D14N S15). The spacer consisted of three proline residues and a four-residue sequence recognized by factor Xa protease. The target was beta-galactosidase. The interaction between the S-peptide portion of the fusion protein and immobilized S-protein allowed for affinity purification of the fusion protein under denaturing (S15 as carrier) or nondenaturing (D14N S15 as carrier) conditions. A sensitive method was developed to detect the fusion protein after sodium dodecyl sulfate-polyacrylamide gel electrophoresis by its ribonuclease activity following activation with S-protein. S-peptide has distinct advantages over existing carriers in fusion proteins in that it combines a small size (> or = 15 residues), a tunable affinity for ligand (Kd > or = 10(-9) M), and a high sensitivity of detection (> or = 10(-16) mol in a gel). PMID- 8453374 TI - Controlling the regiospecificity and coupling of cytochrome P450cam: T185F mutant increases coupling and abolishes 3-hydroxynorcamphor product. AB - Cytochrome P450cam (P450CIA1) catalyzes the hydroxylation of camphor and several substrate analogues such as norcamphor and 1-methyl-norcamphor. Hydroxylation was found experimentally at the 3, 5, and 6 positions of norcamphor, but only at the 5 and 6 positions of 1-methyl-norcamphor. In the catalytic cycle, the hydroxylation of substrate is coupled to the consumption of NADH. For camphor, the degree of coupling is 100%, but for both norcamphor and 1-methyl-norcamphor, the efficiency is dramatically lowered to 12% and 50%, respectively. Based on an examination of the active site of P450cam, it appeared that mutating position 185 might dramatically alter the product specificity and coupling of hydroxylation of norcamphor by P450cam. Analysis of molecular dynamics trajectories of norcamphor bound to the T185F mutant of cytochrome P450cam predicted that hydroxylation at the 3 position should be abolished and that the coupling should be dramatically increased. This mutant was constructed and the product profile and coupling experimentally determined. The coupling was doubled, and hydroxylation at the 3 position was essentially abolished. Both of these results are in agreement with the prediction. PMID- 8453375 TI - Relationship between sequence conservation and three-dimensional structure in a large family of esterases, lipases, and related proteins. AB - Based on the recently determined X-ray structures of Torpedo californica acetylcholinesterase and Geotrichum candidum lipase and on their three dimensional superposition, an improved alignment of a collection of 32 related amino acid sequences of other esterases, lipases, and related proteins was obtained. On the basis of this alignment, 24 residues are found to be invariant in 29 sequences of hydrolytic enzymes, and an additional 49 are well conserved. The conservation in the three remaining sequences is somewhat lower. The conserved residues include the active site, disulfide bridges, salt bridges, and residues in the core of the proteins. Most invariant residues are located at the edges of secondary structural elements. A clear structural basis for the preservation of many of these residues can be determined from comparison of the two X-ray structures. PMID- 8453376 TI - Packing and hydrophobicity effects on protein folding and stability: effects of beta-branched amino acids, valine and isoleucine, on the formation and stability of two-stranded alpha-helical coiled coils/leucine zippers. AB - The aim of this study was to examine the differences between hydrophobicity and packing effects in specifying the three-dimensional structure and stability of proteins when mutating hydrophobes in the hydrophobic core. In DNA-binding proteins (leucine zippers), Leu residues are conserved at positions "d," and beta branched amino acids, Ile and Val, often occur at positions "a" in the hydrophobic core. In order to discern what effect this selective distribution of hydrophobes has on the formation and stability of two-stranded alpha-helical coiled coils/leucine zippers, three Val or three Ile residues were simultaneously substituted for Leu at either positions "a" (9, 16, and 23) or "d" (12, 19, and 26) in both chains of a model coiled coil. The stability of the resulting coiled coils was monitored by CD in the presence of Gdn.HCl. The results of the mutations of Ile to Val at either positions "a" or "d" in the reduced or oxidized coiled coils showed a significant hydrophobic effect with the additional methylene group in Ile stabilizing the coiled coil (delta delta G values range from 0.45 to 0.88 kcal/mol/mutation). The results of mutations of Leu to Ile or Val at positions "a" in the reduced or oxidized coiled coils showed a significant packing effect in stabilizing the coiled coil (delta delta G values range from 0.59 to 1.03 kcal/mol/mutation). Our results also indicate the subtle control hydrophobic packing can have not only on protein stability but on the conformation adopted by the amphipathic alpha-helices. These structural findings correlate with the observation that in DNA-binding proteins, the conserved Leu residues at positions "d" are generally less tolerant of amino acid substitutions than the hydrophobic residues at positions "a." PMID- 8453377 TI - Unnatural amino acid packing mutants of Escherichia coli thioredoxin produced by combined mutagenesis/chemical modification techniques. AB - We have produced several mutants of Escherichia coli thioredoxin (Trx) using a combined mutagenesis/chemical modification technique. The protein C32S, C35S, L78C Trx was produced using standard mutagenesis procedures. After unfolding the protein with guanidine hydrochloride (GdmCl), the normally buried cysteine residue was modified with a series of straight chain aliphatic thiosulfonates, which produced cysteine disulfides to methane, ethane, 1-n-propane, 1-n-butane, and 1-n-pentane thiols. These mutants all show native-like CD spectra and the ability to activate T7 gene 5 protein DNA polymerase activity. In addition, all mutants show normal unfolding transitions in GdmCl solutions. However, the midpoint of the transition, [GdmCl]1/2, and the free energy of unfolding at zero denaturant concentration, delta G(H2O), give inverse orders of stability. This effect is due to changes in m, the dependence of delta G0 unfolding on the GdmCl concentration. The method described here may be used to produce unnatural amino acids in the hydrophobic cores of proteins. PMID- 8453378 TI - Thioflavine T interaction with synthetic Alzheimer's disease beta-amyloid peptides: detection of amyloid aggregation in solution. AB - Thioflavine T (ThT) associates rapidly with aggregated fibrils of the synthetic beta/A4-derived peptides beta(1-28) and beta(1-40), giving rise to a new excitation (ex) (absorption) maximum at 450 nm and enhanced emission (em) at 482 nm, as opposed to the 385 nm (ex) and 445 nm (em) of the free dye. This change is dependent on the aggregated state as monomeric or dimeric peptides do not react, and guanidine dissociation of aggregates destroys the signal. There was no effect of high salt concentrations. Binding to the beta(1-40) is of lower affinity, Kd 2 microM, while it saturates with a Kd of 0.54 microM for beta(1-28). Insulin fibrils converted to a beta-sheet conformation fluoresce intensely with ThT. A variety of polyhydroxy, polyanionic, or polycationic materials fail to interact or impede interaction with the amyloid peptides. This fluorometric technique should allow the kinetic elucidation of the amyloid fibril assembly process as well as the testing of agents that might modulate their assembly or disassembly. PMID- 8453379 TI - Bacterial expression and photoaffinity labeling of a pheromone binding protein. AB - The first high-level production of a binding-active odorant binding protein is described. The expression cassette polymerase chain reaction was used to generate a DNA fragment encoding the pheromone binding protein (PBP) of the male moth Antheraea polyphemus. Transformation of Escherichia coli cells with a vector containing this construct generated clones which, when induced with isopropyl beta-D-thiogalactopyranoside, produced the 14-kDa PBP in both the soluble fraction and in inclusion bodies. Purification of the soluble recombinant PBP by preparative isoelectric focusing and gel filtration gave > 95% homogeneous protein, which was immunoreactive with an anti-PBP antiserum and exhibited specific, pheromone-displaceable covalent modification by the photoaffinity label [3H]6E,11Z-hexadecadienyl diazoacetate. Recombinant PBP was indistinguishable from the insect-derived PBP, as determined by both native and denaturing gel electrophoresis, immunoreactivity, and photoaffinity labeling properties. Moreover, the insoluble inclusion body protein could be solubilized, refolded, and purified by the same procedures to give a recombinant PBP indistinguishable from the soluble PBP. Proton NMR spectra of the soluble and refolded protein provide further evidence that they possess the same folded structure. PMID- 8453380 TI - Structure of recombinant ricin A chain at 2.3 A. AB - The plant cytotoxin ricin is a heterodimer with a cell surface binding (B) chain and an enzymatically active A chain (RTA) known to act as a specific N glycosidase. RTA must be separated from B chain to attack rRNA. The X-ray structure of ricin has been solved recently; here we report the structure of the isolated A chain expressed from a clone in Escherichia coli. This structure of wild-type rRTA has and will continue to serve as the parent compound for difference Fouriers used to assess the structure of site-directed mutants designed to analyze the mechanism of this medically and commercially important toxin. The structure of the recombinant protein, rRTA, is virtually identical to that seen previously for A chain in the heterodimeric toxin. Some minor conformational changes due to interactions with B chain and to crystal packing differences are described. Perhaps the most significant difference is the presence in rRTA of an additional active site water. This molecule is positioned to act as the ultimate nucleophile in the depurination reaction mechanism proposed by Monzingo and Robertus (1992, J. Mol. Biol. 227, 1136-1145). PMID- 8453381 TI - Structure of Paramecium tetraurelia calmodulin at 1.8 A resolution. AB - The crystal structure of calmodulin (CaM; M(r) 16,700, 148 residues) from the ciliated protozoan Paramecium tetraurelia (PCaM) has been determined and refined using 1.8 A resolution area detector data. The crystals are triclinic, space group P1, a = 29.66, b = 53.79, c = 25.49 A, alpha = 92.84, beta = 97.02, and gamma = 88.54 degrees with one molecule in the unit cell. Crystals of the mammalian CaM (MCaM; Babu et al., 1988) and Drosophila CaM (DCaM; Taylor et al., 1991) also belong to the same space group with very similar cell dimensions. All three CaMs have 148 residues, but there are 17 sequence changes between PCaM and MCaM and 16 changes between PCaM and DCaM. The initial difference in the molecular orientation between the PCaM and MCaM crystals was approximately 7 degrees as determined by the rotation function. The reoriented Paramecium model was extensively refitted using omit maps and refined using XPLOR. The R-value for 11,458 reflections with F > 3 sigma is 0.21, and the model consists of protein atoms for residues 4-147, 4 calcium ions, and 71 solvent molecules. The root mean square (rms) deviations in the bond lengths and bond angles in the model from ideal values are 0.016 A and 3 degrees, respectively. The molecular orientation of the final PCaM model differs from MCaM by only 1.7 degrees. The overall Paramecium CaM structure is very similar to the other calmodulin structures with a seven-turn long central helix connecting the two terminal domains, each containing two Ca-binding EF-hand motifs. The rms deviation in the backbone N, Ca, C, and O atoms between PCaM and MCaM is 0.52 A and between PCaM and DCaM is 0.85 A. The long central helix regions differ, where the B-factors are also high, particularly in PCaM and MCaM. Unlike the MCaM structure, with one kink at D80 in the middle of the linker region, and the DCaM structure, with two kinks at K75 and I85, in our PCaM structure there are no kinks in the helix; the distortion appears to be more gradually distributed over the entire helical region, which is bent with an apparent radius of curvature of 74.5(2) A. The different distortions in the central helical region probably arise from its inherent mobility. PMID- 8453383 TI - My life with tryptophan--never a dull moment. PMID- 8453382 TI - Crystal structure of human annexin I at 2.5 A resolution. AB - cDNA coding for N-terminally truncated human annexin I, a member of the family of Ca(2+)-dependent phospholipid binding proteins, has been cloned and expressed in Escherichia coli. The expressed protein is biologically active, and has been purified and crystallized in space group P2(1)2(1)2(1) with cell dimensions a = 139.36 A, b = 67.50 A, and c = 42.11 A. The crystal structure has been determined by molecular replacement at 3.0 A resolution using the annexin V core structure as the search model. The average backbone deviation between these two structures is 2.34 A. The structure has been refined to an R-factor of 17.7% at 2.5 A resolution. Six calcium sites have been identified in the annexin I structure. Each is located in the loop region of the helix-loop-helix motif. Two of the six calcium sites in annexin I are not occupied in the annexin V structure. The superpositions of the corresponding loop regions in the four domains show that the calcium binding loops in annexin I can be divided into two classes: type II and type III. Both classes are different from the well-known EF-hand motif (type I). PMID- 8453385 TI - Adolescent sexual behavior and condom use in Ile-Ife, Nigeria. AB - A study to identify risky sexual behaviors related to condom use was conducted in a Yoruba-speaking urban area of Nigeria. The subjects were 256 randomly selected male high school students, 15-19 years of age, who completed a self-administered questionnaire. The majority (79%, or 194) reported having had heterosexual intercourse in the previous 12 months, 9 (4.6%) with prostitutes and 107 (55.4%) with more than one sexual partner. Three subjects who had more than one sexual partner and 1 of the 9 who had sexual intercourse with a prostitute had used a condom. Condoms were reported to be used only for the prevention of unwanted pregnancy by 61.3% of the students. Implications of these findings for adolescent AIDS education in Africa are discussed. PMID- 8453384 TI - Poly-alpha-amino acids as the simplest protein models: recollections of a retired state president. PMID- 8453386 TI - Effectiveness of a handwashing program. AB - A pilot study to develop and evaluate a program to teach 13 Grade 1 children with disabilities about handwashing was conducted at Glenrose School, which is located within Glenrose Rehabilitation Hospital. Children aged 6 to 8 years were taught how and when to wash their hands. Handwashing skills were evaluated before the teaching began, immediately following the teaching program, and at 1, 3, and 5 months postteaching. The children's handwashing skills did improve, with the girls generally scoring higher than the boys on both washing techniques and times of washing on all the testing occasions. Although the children had fewer visits to the doctor, took fewer prescribed antibiotics, and had fewer infectious illnesses than they did for the same time period the previous year, other variables, in addition to the teaching program, may have contributed to the outcome. A revised handwashing program is now included in the Grade 1 curriculum. PMID- 8453387 TI - A medication discharge planning program: measuring the effect on readmissions. AB - Repeated hospitalizations result in high costs and may occur as a result of patient errors in their medication regimen. To reduce rehospitalizations (hospitalizations within 31 days of the previous discharge), health care professionals have turned to the discharge planning process. Using Orem's theory of self-care, a medication discharge planning program was developed to provide instruction on the requisites necessary for medication self-care. The purpose of this pilot study was to examine the effects of this program on readmissions within 31 days. Five nurses implemented the program for 54 patients with an admitting diagnosis of congestive heart failure. These patients were alternately assigned to a control or an experimental group. The experimental group received the medication discharge planning program. The control group received the usual informal discharge planning provided on the nursing unit. Eight (28.6%) of the 28 patients in the control group were readmitted within 31 days of the previous discharge. Two (7.7%) of the 26 patients in the experimental group were readmitted within 31 days. These results showed a statistically significant difference using Fisher's Exact Test (p = .05). Those receiving the medication discharge planning program were less likely to be readmitted, suggesting the importance of a medication discharge planning program. PMID- 8453388 TI - The significance of pain in children's experiences of hemophilia. AB - The purpose of this research was to document how children with hemophilia describe their experiences with pain in relation to their understanding of their unique illness and treatment experiences. Subjects were 20 children with hemophilia who were between the age of 6 years and 13 years and had no evidence of cognitive problems. Following the principles of grounded theory, data about children's experiences of hemophilia were obtained through a semi-structured interview using five pictorial stimuli representing illness and treatment domains. Data analysis was conducted using the constant comparative method. Findings indicated that pain experiences had a major role in children's perceptions of their illness and treatment experiences and in the meaning attached to these experiences. PMID- 8453389 TI - Submucous resection: is it a simple procedure? AB - With the need to cut costs in the health care system, there has been a rapid increase in the number of surgical procedures performed on an outpatient basis. It is therefore important that patients have enough information to enable them to cope at home. To determine the informational needs of patients undergoing several surgical procedures and examine their postoperative course, a telephone survey was conducted. The results from one group, those undergoing a submucous resection (SMR), stood out. When compared with the 292 patients in the overall study, the 33 SMR patients complained of considerably more discomfort, tiredness, and nausea. Sixty percent of these patients were not satisfied with the information they received. Most would have liked more information about how they would feel postoperatively and how they could cope with their various concerns and problems. The teaching materials and approach to postoperative care for these patients may need to be altered. PMID- 8453390 TI - Multiple sclerosis: the role of social support and disability. AB - This descriptive study explores the types and sources of social support and examines the relationship between types and sources of social support and physical disability and length of illness of 101 individuals with multiple sclerosis. The Norbeck Social Support Questionnaire was used to examine functional support (affect, affirmation, and aid) and structural support (size of network, duration of relationships, and frequency of contact). Findings reveal that subjects perceived "moderate" to "quite a bit" of affect (love, respect, and admiration) but only "moderate" to "little" amounts of affirmation (support of one's thoughts or actions) and tangible aid. Results of multivariate analysis of variance carried out on 44 subjects reveals that subjects perceived more support from spouse/partner than from any other source. Correlational analysis indicates that subjects with higher levels of disability perceived less overall support from spouse/partner and family. Findings also indicate that subjects with a longer period of illness perceived less amount of affect and affirmation and had less contact with network members. PMID- 8453391 TI - Dementia care-receiver needs and their impact on caregivers. AB - This study examines home-based persons with dementia, their needs associated with activities of daily living (ADL), cognitive impairment, and disruptive behaviors, and the relationship of these needs to caregiver distress and burden. Findings suggest that selected disruptive behaviors were most distressing to caregivers, and that when disruptive behaviors occurred more frequently, caregivers were significantly more distressed with these behaviors and reported higher levels of burden. The frequency of cognitive impairment behaviors and level of ADL impairment were not significantly related to caregiver burden, but caregiver distress with these needs was significantly related to caregiver burden. PMID- 8453392 TI - Nursing personnel's perceptions of physical restraint use in long-term care. AB - The use of physical restraints as an accepted clinical intervention was dramatically changed by enactment of legislation in the United States. As a result, nursing personnel's notions of restraints as a therapeutic intervention were challenged. This study was initiated to obtain a better understanding of the underlying motivations for restraint use as a clinical intervention and to provide data helpful to nursing staff as they make the transition to restraint free care. In the study, 124 long-term-care nursing personnel were surveyed regarding their perceptions of restraint use, and were asked whether or not they would recommend using restraints in selected clinical situations. Results of stepwise regression showed that 40% of the variation in the recommendation to use restraints can be explained by the type of nursing personnel (licensed nurse vs. nursing assistant), liability and treatment concerns related to restraint use, age of the nursing staff, and a belief that reducing restraints increases the need for psychoactive medications. PMID- 8453393 TI - Report of the working group on the possible relationship between hepatitis B vaccination and the chronic fatigue syndrome. PMID- 8453394 TI - Ontario hospital outbreak of Salmonella enteritidis infection--agriculture Canada trace-back investigation. PMID- 8453395 TI - Nursing on the Canadian prairies, 1900-1930. Effects of immigration. PMID- 8453397 TI - Guarded by standards and directed by strangers. Charleston, South Carolina's response to a national health care agenda, 1920-1930. PMID- 8453398 TI - "Making do" with the midwife: Arkansas's Mamie O. Hale in the 1940s. PMID- 8453399 TI - "Exchangees" or employees? The exchange visitor program and foreign nurse immigration to the United States, 1945-1990. PMID- 8453400 TI - A profession in caricature. Changing attitudes toward nursing in the American Medical News, 1960-1989. PMID- 8453401 TI - The origins of geriatric nursing. The chronically ill elderly in almshouses and nursing homes, 1900-1950. PMID- 8453402 TI - From almshouse to city nursing home. Philadelphia's Riverview Home for the Aged, 1945-1965. PMID- 8453403 TI - The legacy of domesticity. Nursing in early nineteenth-century America. PMID- 8453404 TI - "Dearest Friend"--the correspondence of colleagues Florence Nightingale and Mary Jones. PMID- 8453405 TI - Restraining the troublesome patient. A historical perspective on a contemporary debate. PMID- 8453406 TI - Old nurses and new. Nursing in the London teaching hospitals before and after the mid-nineteenth-century reforms. PMID- 8453407 TI - Grace under pressure. The nursing Sisters of the Holy Cross, 1861-1865. PMID- 8453408 TI - Medieval nursing. PMID- 8453409 TI - Predictors of outcome following severe head trauma: follow-up data from the Traumatic Coma Data Bank. AB - Outcome as a function of employment status or return to school was evaluated in severely head-injured patients. A priori we selected the most salient demographic, physiological, neuropsychological and psychosocial outcome predictors with the aim of identifying which of there variables captured at baseline or 6 months would best predict employability at 6 or 12 months. Based on the patients evaluated at 6 months, 18% of former workers had returned to gainful employment and 62% of former students had returned to school. For those not back to work or school at 6 months, 31% of the former workers and 66% of the former students had returned by 12 months. Age, length of coma, speed for both attending and motor movements, spatial integration, and intact vocabulary were all significantly related to returning to work or school. The three most potent predictors for returning to work or school were intactness of the patient's verbal intellectual power, speed of information processing and age. PMID- 8453410 TI - Psychosocial outcome in patients with moderate to severe head injury: 2-year follow-up. AB - Psychosocial outcome and recovery of a group of 31 consecutive adult patients with moderate to severe head injuries were prospectively investigated over a 2 year period. A friend control group was used for comparison purposes. We conclude that moderate and severe head injuries have a significant long-term impact on psychosocial functioning. More specifically, although there is an increase over time in the number of subjects who resume former levels of activity, many moderate to severely head-injured people remain unable to work, support themselves financially, live independently and participate in pre-injury leisure activities at least up to 2 years post-injury. Initially, self-perceived limitations in everyday functioning are widespread, with physical functioning being of primary concern. Over time, there is improvement in both physical and psychosocial areas. However, in spite of improvement, difficulties in psychosocial functioning become dominant later due to greater improvement in the physical area. This study gives no evidence of general increase in emotional distress with increasing time since injury. PMID- 8453411 TI - Day-of-injury CT as an index to pre-injury brain morphology: degree of post injury degenerative changes identified by CT and MR neuroimaging. AB - A detailed case study is presented in which pre-injury CT scan findings are compared and contrasted with post-injury CT and MR results in a case of traumatic brain injury (TBI). The day-of-injury scan represented an adequate estimate of pre-injury morphological status based on cross-sectional area measurements of the ventricular system. By comparing pre-injury CT measurements with those obtained on the day of injury, 2 days post-injury and 16 months post-injury via assessing cross-sectional area of select ventricular regions (e.g. anterior and temporal horns, body and third ventricle) it was demonstrated that the TBI induced over a 50% ventricular expansion. Such ventricular expansions are felt to provide some index into diffuse axonal injury which may provide a means of eventually quantifying the degree of structural damage secondary to TBI. This analysis also demonstrated that there were no significant differences between selected cross sectional ventricular areas in the 15 day and 16 month post-injury MR scans. This finding suggests that the degenerative effects of TBI have a rapid onset and are becoming readily apparent by 15 days post-injury. Thus, early imaging may provide a good index of long-term morphological outcome in TBI. PMID- 8453412 TI - Evaluation of needs of high- and low-income families following paediatric traumatic brain injury. AB - This paper assesses the needs of high- and low-income caregivers shortly after the traumatic brain injury of their child. The Family Needs Questionnaire [1], developed to assess the priorities and satisfaction of needs among family members, was administered to 49 caregivers. Surprisingly, caregivers from both groups displayed similar patterns of priorities and rated their most important needs as met. Caregivers' most important needs included clear information, therapy input, and understanding from professionals and classroom teachers. Personal needs, family support, and future patient-related concerns were devalued by both groups. These results are discussed as having implications for identification of high-risk families, treatment goals, and community reintegration needs. PMID- 8453413 TI - Developmental models of social cognition in assessing psychosocial adjustments in head injury. AB - This study compared the levels of conceptual responses involved in the processing of two parameters of social cognition in a group of 40 adult patients with closed head injury (CHI) and a group of 26 normal controls. The two parameters, interpersonal negotiation strategies (INS) and self understanding (self) were examined in the framework of Selman's model of social perspective taking and Damon and Hart's multidimensional model of self understanding. Differences among the components of the INS conflict dilemmas and aspects of self descriptions were observed in a structure interview. Results supported the hypothesis that the CHI group would respond at lower levels on the development measures of social cognition. The results of the present study are in agreement with the conclusions in the initial study. This study also extended the study of social cognition to the Tennessee Self Concept Scale and the Neurobehavioral Rating Scale, in addition to incorporating a control group. These studies support the view that psychosocial adjustment is a multidimensional construct and developmental social cognition methods appear to advance our understanding of this concept in CHI patients. PMID- 8453414 TI - Food intake by brain-injured humans who are in the chronic phase of recovery. AB - This study examined whether survivors of traumatic brain injury differ from normal, non-injured controls in the regulation of food intake in their natural environment. Caregivers of 20 brain-injured subjects and 20 controls recorded in diaries: caloric intake, time of meals, subjective hunger ratings, and the number of persons present during meals for 7 consecutive days. Brain-injured subjects ate larger meals and more total (overall) calories per day compared with controls. In addition, the presence of other people during a meal, or social factor, was a significant predictor of meal size for the control subjects, but not for the brain-injured subjects. Brain-injured subjects also differed from control subjects in their response to pre-meal stomach content. PMID- 8453415 TI - Fifteen-cycle cranial electrotherapy stimulation for spasticity. AB - Severe post-anoxic spasticity in a 25-year-old female was significantly improved during an open trial of 15 cycle per second CES. The bipolar LISS device with suboccipital electrode placement was used for 40 minutes three times a day. A synergism appeared when dantrolene 50 mg twice a day was combined with the CES, these additive effects being greater than either modality used alone. PMID- 8453416 TI - Fluoxetine in treating emotional lability. PMID- 8453417 TI - Predicting outcomes: the slippery slope. PMID- 8453418 TI - Managing and controlling mobile medical equipment: a case study. PMID- 8453419 TI - Providing justification for training: an application of total quality management tools. PMID- 8453420 TI - Building quality into medical product software design. AB - The software engineering and quality assurance disciplines are a requisite to the design of safe and effective software-based medical devices. It is in the areas of software methodology and process that the most beneficial application of these disciplines to software development can be made. Software is a product of complex operations and methodologies and is not amenable to the traditional electromechanical quality assurance processes. Software quality must be built in by the developers, with the software verification and validation engineers acting as the independent instruments for ensuring compliance with performance objectives and with development and maintenance standards. The implementation of a software quality assurance program is a complex process involving management support, organizational changes, and new skill sets, but the benefits are profound. Its rewards provide safe, reliable, cost-effective, maintainable, and manageable software, which may significantly speed the regulatory review process and therefore potentially shorten the overall time to market. The use of a trial project can greatly facilitate the learning process associated with the first time application of a software quality assurance program. PMID- 8453421 TI - Electroencephalographic scalp-energy analysis as a tool for investigation of cognitive performance. AB - In a new method of using electroencephalography (EEG) to monitor cognitive events, multichannel event-related potentials (ERPs) were used to estimate scalp distributions of surface energy densities of cortically generated electrical fields. Cross-subject regression analyses were then used to map sites and post stimulus latencies, for which there is a high correlation of energy densities with subjects' performances. In a preliminary study, five right-handed young men were presented mental arithmetic tasks via a computer screen. A 21-channel ERP was computed for each subject and converted to show the scalp distribution of energy density at each sampling period (every 7.8 msec). Indices of subjects' task performances were regressed upon these estimates of potential energy at each electrode site and post-stimulus latency. High correlations were found at four distinct regions and latencies. These corresponded to the stages and sites of cortical localization for mental arithmetic inferred from studies of patients with localized cortical lesions. This correspondence suggests that the EEG procedure may offer an inexpensive, noninvasive method of investigating cortical localization of cognitive function in healthy subjects. PMID- 8453422 TI - A new bladder stimulator--hand-held controller and miniaturized implant: preliminary results in dogs. AB - A new urinary-tract stimulator that is intended to restore normal bladder function to patients who have spinal-cord injuries is described. The system is composed of two principal parts. The first, which is external, consists of a hand held device based on an inductive-coupling technique. This controller incorporates all the circuitry necessary to transmit data transdermally. The second, a fully programmable implantable device, includes a complementary metal oxide semiconductor gate-array integrated circuit controlling eight monopolar (or four bipolar) stimulation channels. To protect the tissues and the device, three different biocompatible polymers encapsulate the implant. In the experimental phase, the authors investigated the effect of early electrical stimulation of the bladder during the spinal-shock phase in paraplegic dogs. In addition, using the stimulator, they localized the parameters of stimulation that give the best results in terms of effective bladder pressure and voiding a high volume of urine. PMID- 8453423 TI - Development of a high-precision continuous extracorporeal hemodiafiltration system. AB - A high-precision hemofiltration system appropriate for use in neonatal, pediatric, or adult patients has been developed. The system incorporates computer monitored and -regulated pumps for control of blood, dialysate, and drain solutions and weighing scales for measurement of fluid infused into and removed from the patient. The overall accuracy of the fluid infusion and withdrawal is +/ 3.5 grams. The system incorporates four pressure transducers to monitor pressures. It includes alarm limits for pressure, solution volumes versus time, temperature, air leak, and blood detection in the drain effluent. The computer stops all pumps in alarm conditions. The system also can be easily adapted for other extracorporeal procedures such as hemofiltration, ultrafiltration, plasmapheresis, and extracorporeal membrane oxygenation. PMID- 8453424 TI - Long-term outcome in personality disorders. AB - Personality disorders meeting DSM or ICD criteria represent the severe end of the broad spectrum of personality configurations involving maladaptive traits. The literature regarding long-term outcome of personality disorders is sparse. Most attention is devoted to formerly institutionalised patients with borderline, antisocial, or schizotypal disorders. Borderline patients at 10-25-year follow-up have a wide range of outcomes, from clinical recovery (50-60%) to suicide (3-9%). Certain factors (e.g. artistic talent) conduce to higher recovery rates, others (e.g. parental cruelty) to lower rates. Schizoid and schizotypal patients tend to remain isolated, and to lead marginal lives. The long-term outcome in antisocial persons is bleak if psychopathic traits are prominent. Personality traits and their corresponding disorders are egosyntonic, harden into habit, and are both slow to change and hard to modify. There is no one treatment of choice. Psychoanalysis and related methods work best within the anxious/inhibited group; cognitive/behavioural techniques are well suited to the disorders requiring limit setting and the amelioration of maladaptive habits. PMID- 8453425 TI - Homelessness and mental illness. AB - In Great Britain 1-2 million people may be homeless. Most homeless people are men, but about 10-25% are women, of whom about half are accompanied by children. Significant mental illness is present in 30-50% of the homeless: functional psychoses predominate; acute distress and personality dysfunction are also prevalent. Co-morbidity of mental illness and substance abuse occurs in 20%, and physical morbidity rates exceed those of domiciled populations. The homeless mentally ill also have many social needs. Pathways to homelessness are complex; deinstitutionalization may be only one possible cause of the increase in the number of homeless people. There is much recent research estimating the extent of mental illness and the characteristics of selected subgroups of accessible homeless people. The evaluation of potential service solutions has received less attention. This review outlines the research, highlights current views on the definition and classification of homeless populations, and offers some guidelines on avenues which need to be explored. PMID- 8453426 TI - Diversion from custody. I: Psychiatric assessment at the magistrates' court. AB - The homeless mentally disordered defendant facing minor charges poses considerable problems regarding appropriate disposal. Psychiatric assessment may be required in order to facilitate the court's decision, but this is often available only after remand in custody. A psychiatric assessment service based at two inner-London magistrates' courts is described. Over 18 months, 201 defendants were referred. They were predominantly male, single, and of no fixed abode, suffering from serious psychiatric disorder; these defendants had often received previous in-patient treatment, frequently as detained patients. They typically were recidivists charged with minor offences. Following initial assessment, 25% were admitted to hospital, 50% were released, and 25% returned to custody. The Crown Prosecution Service discontinued 29% of cases. For those admitted directly to hospital, the mean (s.d.) time from arrest to hospital admission was 5.8 (6.8) days, significantly quicker than with prison-based assessments. PMID- 8453427 TI - Diversion from custody. II: Effect on hospital and prison resources. AB - Two hundred and one referrals to a psychiatric assessment scheme based at two inner-London magistrates' courts were followed up to assess the effect of the scheme on hospital and prison resources. Of the 65 hospital admissions, 50 (77%) derived some or marked benefit from psychiatric treatment. Those who did badly were more likely to be of no fixed abode, and had higher rates of criminality and previous compulsory admission to hospital. Absconding was the largest management problem; 30 (46%) of those admitted did so. Twelve months after admission, all patients except one had been discharged; 10 (15%) had been readmitted to hospital. The scheme generated an extra 21 (64%) hospital admissions per annum from the two courts, compared with the three years before its introduction. The saving in remand time to the prison was approximately double the increased admission time to hospital. However, the overall effect of early diversion on hospital and prison resources was small. PMID- 8453428 TI - Does recollection of exposure to poor maternal care in childhood affect later ability to relate? AB - The study tested Bowlby's hypothesis that experiencing the poor relating of parents in childhood predisposes the individual to poor relating in adult life. Data were drawn from two community samples: a younger sample of 25-34-year-old married women, and an older one of 40-49-year-old women. Data were also drawn from the husbands of the women in the younger sample. It focused on the single childhood variable of the recollection of poor maternal care. To avoid the effect of this on depression or other psychopathology, groups who were depressed and not depressed, or who were at different levels of psychopathology, were examined separately. Recollection of poor early care was associated with poor relating, lower age at marriage, poor-quality marriage and divorce from first marriage. There was a suggestion that the effects of the recollection of poor early care of marital partners summate. PMID- 8453429 TI - In-patient treatment of 165 adolescents with emotional and conduct disorders. A study of outcome. AB - A two-year follow-up study of 165 teenagers with conduct and emotional disorders treated as in-patients on a regional adolescent unit (YPU) is described. The target types of behaviour for each subject were scored independently by the teenager, the parent or guardian, and the professional referrer before admission and at one month, one year and two years after discharge. The significant overall improvement in behaviour observed at one month after discharge was sustained at one and two years. Thirty-three subjects who abandoned treatment within six weeks of admission had made significantly less progress than the fully treated group at one month after discharge, but there were no significant differences at the one- and two-year evaluations. Two years after treatment, between 69% and 79% of the 132 subjects who completed treatment were regarded as improved, depending on which respondent made the assessment. Adolescents who completed treatment had different characteristics from those who terminated treatment prematurely and were more likely to be girls in care referred by social services. PMID- 8453430 TI - Parental ideas of normal and deviant child behaviour. A comparison of two ethnic groups. AB - The parents of Gujarati and English children were interviewed and their attitudes to a wide range of child behaviour elicited. Differences in their ideas of normal and deviant behaviour were found in areas such as conduct and bedwetting, but not in self-care. PMID- 8453431 TI - Stress incubation and the onset of affective disorders. AB - Incubation is the process by which life events influence the onset of psychiatric disorder after an appreciable delay. It has long been recognised clinically. In this paper we use data from the Camberwell Collaborative Depression Study to see whether incubation effects can be demonstrated in depressive illness. We used a novel adaptation of survival analysis for this purpose. The results suggest that incubation does occur in depressive disorder, that it is much less important than the effect of life events close to onset, that it is apparent in women but not in men, and that it is no more evident preceding endogenous than neurotic symptom patterns. PMID- 8453432 TI - The efficacy and tolerability of combined antidepressant treatment in different depressive subgroups. AB - Eighty patients admitted to hospital with major depression were randomly allocated to six weeks of treatment with tranylcypromine, amitriptyline, or tranylcypromine and amitriptyline in combination, in a double-blind study. Scores on the HRSD improved significantly in all three groups, but there were no differences between the three groups. Patients on tranylcypromine and amitriptyline combined improved more according to their self-ratings after six weeks, and response was earlier as measured by a clinical global improvement scale. Those with endogenous depression improved more than those with neurotic depression, irrespective of treatment group. Combined treatment was less well tolerated than single treatments and gave rise to more side-effects, although there was no serious toxicity. Orthostatic hypotension was observed more frequently in patients on combined treatment. This group also experienced a significant increase in weight and prolongation of the P-R interval on ECG. PMID- 8453433 TI - 'Neurosis' and the personal social environment. The effects of a time-limited course of intensive day care. AB - The Interview Schedule for Social Interactions (ISSI) was used to assess the social environment of 65 British inner-city patients suffering from severe neurotic disorder; all patients were offered a 12-week course of intensive day treatment with an educational and psychodynamic basis. Compared with a general population in Canberra, the neurosis sufferers had lower (morbid) scores on the ISSI for the extent and quality of their social relationships. Of the 34 subjects who completed treatment and attended for the post-treatment investigation, 21 attained a PSE score below the level for 'caseness'. Twenty-five subjects who attended for follow-up at 18-24 months had improved significantly on all four of the standard ISSI measures, although they had not done so immediately after treatment. This suggests that although symptoms may improve at the time of treatment, social relationships improve only over several months. PMID- 8453434 TI - A new community mental health team based in primary care. A description of the service and its effect on service use in the first year. AB - A new community multidisciplinary team based in primary care is described and the experience of the first year discussed. The effect the team has had on the use of psychiatric services in its first year was studied. There was a threefold increase in the rate of inception to care, leading to a doubling in the prevalence of treated psychiatric disorder. There has been a reduction in the demands made on the hospital out-patient services, but no change in the use of in patient resources or emergency contacts. PMID- 8453435 TI - The Lewy-body variant of Alzheimer's disease. Clinical and pathological findings. AB - At post-mortem, Lewy bodies (LBs) were found in the brainstem and neocortex of eight out of 65 patients who had been collected during a prospective long-term study on clinically diagnosed Alzheimer's disease. All eight patients had accompanying Alzheimer pathology which was less severe than in a sample of eight age- and sex-matched patients from the same study with neuropathologically verified Alzheimer's disease. Parkinsonian features were more common in patients with LBs. There were no particular differences in duration of illness, severity of cognitive impairment, presence of hallucinations, or fluctuations in the course of illness. Frontal cerebral atrophy was more marked in patients with LBs, as was the loss of neurons in the basal nucleus of Meynert and the substantia nigra. Cognitive performance correlated with the number of pigmented neurons in the substantia nigra. We conclude that the differential diagnosis of LB dementia should be considered in patients satisfying NINCDS-ADRDA criteria for Alzheimer type dementia who show marked Parkinsonian features and a frontal accentuation of cerebral atrophy. PMID- 8453436 TI - The Nithsdale schizophrenia surveys. XI: Relatives' expressed emotion. Stability over five years and its relation to relapse. AB - The level of expressed emotion (EE) in 32 relationships between relatives and schizophrenic patients was assessed on three separate occasions over five years. EE was high on all three occasions in 25% of relatives, low on all three in 38%, and fluctuating in 38%; that is, in the majority of relatives (63%) the level of EE was stable over time. Three relatives who had previously shown high EE had evidence of dementia at the time of the third assessment, and showed low EE. Fourteen patients relapsed at least once over five years; patients who relapsed were evenly spread throughout those living in a home in which EE was consistently high, consistently low, or fluctuating. However, patients living in low-EE homes who did relapse did so significantly less often than those who relapsed and were living in homes in which EE was high or fluctuating. At the time of relapse, EE was not consistently high, and some patients in consistently high-EE homes did not relapse at all over five years. PMID- 8453437 TI - Gastric emptying, body weight and symptoms in primary anorexia nervosa. Long-term effects of cisapride. AB - In a double-blind trial, 12 out-patients with primary anorexia nervosa received, for six weeks, either 10 mg cisapride or placebo, three times a day. Cisapride accelerated gastric emptying of a radiolabelled semisolid meal in all six patients; five gained weight and symptoms of gastric retention ameliorated in four. With placebo, three of six had emptying enhanced, four gained weight, and one's symptoms improved. For another six weeks, all patients received cisapride. In five of the patients who had received cisapride, emptying further accelerated or remained stable; in one it slowed. Of the six patients who received placebo, four had emptying accelerated, five gained weight, and symptoms improved in four. Longer administration of cisapride may, by enhancing gastric motor activity, alleviate symptoms of retention and thus help to change eating behaviour. PMID- 8453438 TI - Towards a cognitive-behavioural theory of problem gambling. AB - A heuristic model to account for the development and maintenance of problem gambling is provided with the aim of directing clinical management and future research. Previous explanations of problem gambling have been limited in two main ways. Firstly, the models have been primarily descriptive, and secondly they have generally lacked clinical value. Most explanations have ignored the mechanisms through which this behaviour becomes problematic, and have not identified the relationships between different variables. PMID- 8453439 TI - Human sleep, sleep loss and behaviour. Implications for the prefrontal cortex and psychiatric disorder. PMID- 8453440 TI - Duration of depressive illness. PMID- 8453441 TI - Propofol and ECT. PMID- 8453442 TI - Suicide prevention by general practitioners. PMID- 8453443 TI - Psychosis and multiple sclerosis. PMID- 8453444 TI - Adaptive Behaviour Scale in Down's syndrome. PMID- 8453445 TI - Fluoxetine and suicidal behaviour. PMID- 8453446 TI - Periodic psychosis associated with the menstrual cycle and childbirth. PMID- 8453447 TI - Gender differences in schizophrenia. PMID- 8453448 TI - Carbamazepine and episodic dyscontrol. PMID- 8453449 TI - SSRIs and tricyclic antidepressants. PMID- 8453450 TI - HTLV-1 revisited. PMID- 8453451 TI - The effects of opium smoking. PMID- 8453452 TI - Functional mapping of brain areas implicated in auditory--verbal memory function. AB - Positron emission tomography measurements of regional cerebral blood flow (rCBF) were performed in normal volunteers during two auditory--verbal memory tasks: a subspan and supraspan task. The difference in rCBF between tasks was used to identify brain areas/systems involved in auditory--verbal long-term memory. Increases in rCBF were observed in the left and right prefrontal cortex, precuneus and the retrosplenial area of the cingulate gyrus. Decreases in blood flow were centred in the superior temporal gyrus bilaterally. Separate comparisons were also made between each span task and a resting state. Brain regions showing increases in rCBF in these comparisons included the thalamus, left anterior cingulate, right parahippocampal gyrus, cerebellum and the superior temporal gyrus. The brain areas identified in these comparison define a number of the neuroanatomical components of a distributed system for signal processing and storage relevant to auditory--verbal memory function. PMID- 8453453 TI - Prognostic factors in a multiple sclerosis incidence cohort with twenty-five years of follow-up. AB - An incidence cohort consisting of 308 multiple sclerosis patients was followed up repeatedly during at least 25 years of disease. A number of clinical factors were analysed with respect to their validity in assessing the long-term prognosis. Of the onset characteristics, the type of course was the most important, with primary progressive patients experiencing a much more severe course. In patients with an acute onset, low onset age, high degree of remission at first exacerbation, symptoms from afferent nerve fibres and onset symptoms from only one region (as compared with polyregional symptoms) of the central nervous system, were factors significantly associated with a favourable long-term prognosis. Of factors known 5 years after onset, a low number of affected neurological systems, a low neurological deficit score and a high degree of remission from the last bout were the most important favourable prognostic factors. PMID- 8453454 TI - The significance of brain magnetic resonance imaging abnormalities at presentation with clinically isolated syndromes suggestive of multiple sclerosis. A 5-year follow-up study. AB - A 5-year follow-up study was performed on 89 patients who had undergone brain magnetic resonance imaging (MRI) at presentation with an acute clinically isolated syndrome of the optic nerves, brainstem or spinal cord of a type suggestive of multiple sclerosis. At presentation, MRI was abnormal, revealing one or more asymptomatic cerebral white matter lesions in 57 (64%), and was normal in 32 (36%). At follow-up, progression to clinically definite multiple sclerosis had occurred in 37 out of 57 (65%) with an abnormal MRI and one out of 32 (3%) with normal MRI. Human leucocyte antigen (HLA) typing was performed in 70 patients and cerebrospinal fluid (CSF) was examined at presentation in 36. The presence of HLA-DR2 antigen or cerebrospinal fluid oligoclonal IgG bands were both associated with a significantly increased risk of progression to multiple sclerosis, but MRI was much more powerful in predicting outcome. The presence of four or more MRI lesions at presentation was associated with a higher rate of progression to multiple sclerosis, more frequent development of moderate or severe disabilities and a greater number of new MRI lesions at follow-up. The results indicate that brain MRI at presentation with a clinically isolated syndrome suggestive of multiple sclerosis is a powerful predictor of the clinical course over the next 5 years. This observation, combined with an ability to detect other sometimes treatable disorders which can also cause such syndromes, suggests that MRI is the investigation of choice in evaluating this group of patients. PMID- 8453455 TI - Very small (border zone) cerebellar infarcts. Distribution, causes, mechanisms and clinical features. AB - Computerized tomography (CT) and magnetic resonance imaging (MRI) allow accurate anatomical localization of large thromboembolic cerebellar infarcts in the territories of the cerebellar arteries and their branches. In addition, MRI and CT show very small cerebellar infarcts as discrete foci of signal change that are not easily localizable within well-defined arterial territories. They could be border zone infarcts. Their anatomy, mechanism and clinical features have not been studied. By reviewing our CT and MRI files over a 2-year period, we found 47 patients with very small cerebellar infarcts; 23 patients had angiography. Infarcts were cortical (32 patients), deep (10 patients) and both (five patients). Most lesions corresponded to border zone cerebellar infarcts. The mechanisms of infarction were (i) global hypoperfusion due to cardiac arrest (two patients); (ii) small or end (pial) artery disease due to intracranial atheroma or hypercoagulable states (nine patients); (iii) focal cerebellar hypoperfusion due to large artery (vertebral or basilar) occlusive disease (16 patients) or brain embolism (11 patients) resulting in infarcts in the watershed areas (27 patients total); (iv) unknown mechanism (nine patients, 19%). Large artery occlusive disease was more frequently observed in deep than in cortical infarcts (9 out of 15 versus 11 out of 37; P < 0.0001). The most frequent symptoms were dizziness, lightheadedness, unsteadiness with axial lateropulsion, dysarthria and limb clumsiness. These symptoms were either transient or recurrent, at times related to positional changes of the head or trunk. Position-related symptoms often persisted for weeks or months after the ischaemic event, and occurred mainly in patients with combined carotid and vertebrobasilar occlusive disease. Physical findings were either absent or included wide-based gait, lateropulsion, mild ipsilateral dysmetria, dysarthria or dysdiadochokinesia. We conclude that very small cerebellar infarcts are often found on CT and MRI. Their border zone distribution and frequent posturally related symptoms most often result from large or pial artery disease rather than from systemic hypotension. PMID- 8453456 TI - Ischaemia-induced (symptomatic) migraine attacks may be more frequent than migraine-induced ischaemic insults. AB - Fifteen consecutive patients with a diagnostic problem of ischaemia-induced migraine with aura (symptomatic migraine) or migraine-associated ischaemia (migrainous infarction) were studied in order to elucidate the mechanisms. Three had a 1 month flurry of daily attacks of migraine auras with or without headache. A severe internal carotid stenosis/occlusion and reduced regional cerebral blood flow (rCBF) was demonstrated. Borderline ischaemia may thus prime the brain for developing migrainous aura with or without migraine (symptomatic migraine). Four patients had a combination of permanent deficits after the very first migraine attack, severe atherosclerosis, risk factors for stroke, high age and no family history of migraine. In these cases the evidence indicates that thromboembolic ischaemia had triggered an attack of migraine with aura (likely symptomatic migraine). Three young females presented long-lasting typical and severe idiopathic migraine with aura. Attack-associated rCBF reduction was likely to have caused permanent, mild, visual or somatosensory deficits (migrainous infarction). In five patients the relationship between migraine and stroke remained unresolved. It seems that ischaemia-induced migraine attacks may be more frequent than migraine-induced ischaemic insults. Therefore, migraine is not as strong a risk factor for stroke as indicated by the mere coincidence of the two disorders. PMID- 8453457 TI - Changes in shapes of surviving motor neurons in amyotrophic lateral sclerosis. AB - In amyotrophic lateral sclerosis, motor neurons in the spinal cord and brainstem shrink before they die. In 12 cases of sporadic amyotrophic lateral sclerosis, and in 11 control subjects, we have measured the neurons in the second sacral segment and the hypoglossal nucleus, and have calculated a 'shape index' that shows the convexity or concavity of the cell body. (The shape index, SI = 100 x C/P, where C is the circumference of the largest circle that can be inscribed in the neuron and P is the perimeter of the perikaryon, including the bases of the dendrites as seen in a Nissl preparation. The shape index increases with increasing convexity of the cell.) In the ventral horn of segment S2 and in the hypoglossal nucleus, the surviving motor neurons in amyotrophic lateral sclerosis showed significantly decreased size and increased shape index (convexity) of the cell bodies. By contrast, the nucleus of Onuf in segment S2, consisting of neurons that supply the pelvic floor muscles, was preserved in amyotrophic lateral sclerosis. Its cells did not differ significantly in size or convexity between the amyotrophic lateral sclerosis and control groups. In both the hypoglossal and S2 neuronal populations in amyotrophic lateral sclerosis, the sizes of the cells were positively correlated with the numbers of surviving motor neurons. However, there was no correlation of the shape index with numbers of cells. This is interpreted as due to shrinkage of neurons still taking place at the time of death, when the changes in shape were probably largely completed. These observations indicate that the mechanism of neuronal atrophy in amyotrophic lateral sclerosis may involve both reduced protein synthesis and enzymatic degradation of the cytoskeleton within the larger dendrites. PMID- 8453458 TI - Reading in pure alexia. The effect of strategy. AB - A number of investigators have demonstrated that patients with pure alexia comprehend briefly presented words which they are unable to explicitly identify. We suggested previously that these patients may read by means of two distinct procedures: a laborious letter-by-letter method and a 'whole-word' procedure which, at least initially, does not support explicit word identification. We report a test of this proposal in a patient with pure alexia. We reasoned that if the patient had access to two distinct and incompatible procedures, he might be induced to switch from one to the other by changing task demands. We found that when instructed to name words, the patient employed a letter-by-letter strategy; in contrast, when instructed to make lexical decision or semantic judgements about rapidly presented words, he appeared to use a 'whole-word' strategy. These data support the hypothesis that two distinct procedures are available to this patient. We argue, further, that is necessary to suppress use of the letter-by letter strategy to demonstrate whole word reading capability in pure alexics, and that failure to do so may account for negative findings in other cases reported in the literature. PMID- 8453459 TI - Vacuolar myopathy sparing the quadriceps. AB - Twenty-two Jewish patients, belonging to 15 families, 11 of them from Iran and three possibly of Iranian stock, suffered from progressive muscle weakness and wasting. The initial symptom was usually distal leg muscle weakness, appearing in the third or fourth decade and insidiously involving the proximal muscles and to a lesser extent the upper limbs. The quadriceps muscle was consistently spared even in advanced cases. Computerized tomography (CT) scans of muscles demonstrated variable wasting and fatty replacement of limb and axial muscles, while the vastus lateralis muscle retained its normal CT appearance. The typical light microscopy features of the affected muscles were: presence of vacuoles within muscle fibres, internal nuclei, longitudinal fibre splitting and, in severely affected muscles, endomysial fibrosis without, inflammation or fibre necrosis. Electron microscopy suggested that the vacuoles were autophagic. Cytoplasmic and intranuclear inclusions were rare. While electromyography (EMG) revealed presence of spontaneous activity, however, analysis of muscle action potentials, turns-amplitude ratio, macro-EMG and single fibre EMG suggested a primary myopathic disorder. Consanguinity in seven families, the parents being first cousins, and the presence of additional affected siblings of both sexes may suggest an autosomal recessive trait. The presence of this disorder in Iranian Jews may indicate that this is a distinct myopathic entity. PMID- 8453460 TI - The effect of sympathetic blockade on facial sweating and cutaneous vascular responses to painful stimulation of the eye. AB - The vascular response in the forehead to stimulating the eye with soapy water was investigated in 15 subjects shortly after pharmacological blockade of the stellate ganglion. Electrodermal activity was also recorded from each side of the forehead in nine subjects. Pulse amplitude and electrodermal activity increased on the stimulated side of the forehead. Sympathetic blockade had no consistent effect on the vascular response, which was similar in magnitude on the blocked and sympathetically intact sides. In contrast, the electrodermal response was greater on the blocked side of the forehead, suggesting that sympathetic blockade had removed an inhibitory influence. The findings demonstrate that cervical sympathetic outflow does not increase vasodilatation or local sweating in the forehead during painful stimulation of the eye. Conjunctival irritation induces a trigeminal-parasympathetic vasodilator reflex in the forehead circulation. Release of vasoactive intestinal polypeptide from parasympathetic terminals during this reflex might increase local sweating. PMID- 8453461 TI - The role of premotor cortex and the supplementary motor area in the temporal control of movement in man. AB - In the present study temporal control of movement was systematically analysed in patients with unilateral lesions of the lateral or medial premotor cortex (PMC) or supplementary motor area (SMA) and in age-matched controls. The ability to learn new temporal adjustments was evaluated by examining rhythm reproduction using either the left or right hand or both hands in an alternating manner. A severe impairment in rhythm reproduction was found after lateral or medial PMC lesions; the deficit was most pronounced when our patients were required to use both hands in an alternating manner. The impairment occurred in the absence of difficulties in manual dexterity or impairments in discriminating the rhythm patterns. In a second series of experiments the contribution of the SMA in organizing movements in the time domain was examined. In this series, two patients with left-sided lesions, including the SMA but sparing tissue from the lateral hemispheric surface, and seven age-matched controls were requested to reproduce rhythm constellations in the presence of a sound signal and from memory. Results reveal that patients with left medial lesions involving the SMA had most severe difficulties to produce any rhythms from memory, though they were able to produce the rhythms under auditory pacing. This deficit in programming sequential patterns from memory in the time domain should be interpreted in the context of a decline in the ability to benefit from previous stimulus presentation, which prevents an effective later programming of these sequences when they have to be rehearsed from memory. It was found that patients with left SMA lesions had an increase in reaction time on a sequential digit task when sequences had to be produced under delayed conditions; by contrast, the controls showed a decrease of reaction time after previous stimulus presentation. The present findings extend previous knowledge on sequential motor tasks and argue for a critical role for both the SMA and the premotor cortex in the generation of sequences from memory that fit into a precise timing plan. PMID- 8453462 TI - Thalamic stimulation and suppression of parkinsonian tremor. Evidence of a cerebellar deactivation using positron emission tomography. AB - Parkinsonian tremor can be abolished by chronic high frequency thalamic stimulation of the ventral intermediate nucleus. We have studied six patients with unilateral Parkinson's disease. The patients had an electrode chronically implanted in the ventral intermediate nucleus of the thalamus. We measured changes in cerebral activity by positron emission tomography using an index of regional cerebral blood flow (rCBF). Each patient was scanned in three states: (i) tremor without stimulation (condition A); (ii) tremor with ineffective stimulation (condition B); (iii) tremor abolished by effective stimulation (condition C). The suppression of tremor (C compared with B) was specifically associated with a decrease of rCBF in the cerebellum, whereas the ineffective stimulation (B compared with A) induced a decrease of rCBF in homolateral cerebral cortex. The results give evidence for different contributions from cortex and cerebellum to the generation of parkinsonian tremor and suggest that tremor suppression is mainly associated with a decrease of synaptic activity in the cerebellum. PMID- 8453463 TI - Pathological overlap in cases of parkinsonism associated with neurofibrillary tangles. A study of recent cases of postencephalitic parkinsonism and comparison with progressive supranuclear palsy and Guamanian parkinsonism-dementia complex. AB - In recent years a number of patients suffering from long-standing postencephalitic parkinsonism have donated their brains to the United Kingdom Parkinson's Disease Society Brain Bank, in London. In view of the paucity of detailed neuropathological reports of the disease since the 1940s, we have carried out a clinicopathological study of eight recent cases. A spectrum of pathological change was seen, with highly variable involvement of cortical, subcortical and brainstem structures. There was no correlation between severity of disease and severity of pathology. The anatomical distribution of lesions was compared with that seen in progressive supranuclear palsy and Guamanian Parkinson dementia complex. No definite histological features were identified that could distinguish any of the three disease entities. While the pathogenesis of postencephalitic parkinsonism, progressive supranuclear palsy and Guamanian Parkinson-dementia complex remains unknown, the presence of similar pathologies in these conditions suggests a common disease mechanism, despite the distinctive clinical features. PMID- 8453464 TI - Plasticity of the sensorimotor cortex representation of the reading finger in Braille readers. AB - We studied the organization of the somatosensory cortex in proficient Braille readers, recording somatosensory evoked potentials (SEPs) in 10 subjects and using transcranial magnetic stimulation (TMS) in five subjects, and compared the results with those of 15 control subjects. Somatosensory evoked potentials were elicited by a focal electrical stimulus to the tip of the index finger and recorded from a contralateral 4 x 4 grid of scalp electrodes centred around C3' and C4'. Transcranial magnetic stimulation, with an 8-shaped coil centred over the same scalp positions, was delivered simultaneously with, and at different intervals after, the finger stimulus. The results of the right index (reading) finger in Braille readers were compared with those of their left index (non reading) finger and of the right and left index fingers of the control subjects. The scalp areas from which we recorded N20 and P22 components of the SEP with an amplitude of at least 70% of the maximal amplitude recorded in each trial were significantly larger in SEPs evoked from the reading fingers. Detection of the stimulus applied to the reading finger was blocked by TMS delivered over a larger contralateral scalp area and during a longer time window after the stimulus. These experiments suggest that reading Braille is associated with expansion of the sensorimotor cortical representation of the reading finger. PMID- 8453465 TI - Sound localization in acallosal human listeners. AB - In order to evaluate the callosal and hemispheric involvement in sound localization, the present study examined response accuracy to auditory targets in acallosal subjects. The primary interest was to determine whether the congenital absence of the corpus callosum affects auditory localization, especially for sounds situated near the midline of auditory space or moving across it. A corollary objective was to examine the possible existence of an hemispheric asymmetry on audio-spatial localization tasks. Four subjects with callosal agenesis paired to four age and IQ-matched controls and 16 normal control subjects were asked to locate broad band noise bursts at fixed intensity (52 dB sound pressure level) in the horizontal plane in an anechoic chamber. Broad band noise bursts were delivered randomly through 16 loudspeakers, which were mounted at approximately 10 degrees intervals on a perimeter frame. Two conditions were tested: (i) localization of a fixed-sound source; (ii) localization of the beginning and the end of a simulated moving stimulus. Two response modes were used. Listeners reported the apparent stimulus location either (i) by pointing with the ipsilateral index finger or (ii) by calling out the estimated angles indicated on the calibrated sound perimeter. Aiming accuracy was assessed by calculating the mean deviation of the response from the objective target position. The results indicated that the responses of the acallosal subjects were less accurate than those of the controls. The deficit was observed not only at the midline but throughout the auditory field. This points to possible compensatory mechanisms following the early absence of the corpus callosum which are, however, limited. The results obtained with manual pointing were generally more precise than those obtained through oral responses. This difference suggests that the remapping of spatial positions onto a verbally based coordinate system involves a supplementary cognitive step which affects the precision of the response. Comparing the performance to stimulus presentation in the left and right fields indicated that no hemispheric asymmetry was apparent under any of the conditions for either the acallosal subjects or the IQ-matched and normal control subjects. PMID- 8453466 TI - Exploring somatosensory hemineglect by vestibular stimulation. AB - The effects of vestibular stimulation upon somatosensory deficits or tactile extinction contralateral to a hemispheric lesion were investigated in 20 right brain-damaged patients and 11 left brain-damaged patients. After stimulation, right brain-damaged patients showed a temporary partial recovery from left hemianaesthesia or extinction. Conversely, right somatosensory deficits associated with left brain damage were virtually unaffected by vestibular stimulation. Temporary recovery from somatosensory deficits was independent of the presence of visuo-spatial hemineglect. The suggestion is made that somatosensory deficits and extinction produced by right brain damage have an important non-sensory or perceptual component, that may be positively affected by vestibular stimulation. The mechanisms whereby this treatment may ameliorate somatosensory deficits may involve the restoration of the normal correspondence between somatotopic and egocentric representations of the body. PMID- 8453467 TI - Absence of frontal somatosensory evoked potentials in Huntington's disease. AB - A fast route for transmission of deep and cutaneous afferent information to the frontal cortex is well established in non-human primates. Whether the incoming cortical information gives rise to early frontal somatosensory evoked potentials (SEPs) in humans is still a matter of contention. We attempted to solve this question by investigating the topography of SEP generators evoked by median nerve stimulation in 30 healthy subjects and in 30 patients suffering from Huntington's disease, who are known to have reduced SEP amplitudes. Using an earlobe reference, SEPs were recorded with an array of either five surface electrodes over the contralateral parietal cortex or 32 electrodes distributed over the whole scalp. In normal subjects analysis of frontal potentials revealed an early positive (P22) and negative (N30) component which could not be explained by generators located in the parietal cortex. Apart from the reduction of parietal components (N20, P25) frontal P22 and N30 were diminished or absent in Huntington's disease patients. Frontal potentials were even reduced in those patients who had parietal SEP amplitudes within the range of normal subjects. These frontal changes are similar to those reported in other basal ganglia disorders. Basal ganglia dysfunction might therefore be associated with changes of frontal SEP components. PMID- 8453468 TI - Sensitization of c-fos expression in rat striatum following multiple challenges with D-amphetamine. AB - D-Amphetamine transiently stimulates the expression of the immediate-early response gene, c-fos, in rat striatal cell nuclei. D-Amphetamine (2.5 mg/kg i.p.) induced a significantly greater expression of Fos-like immunoreactivity in striatum of rats treated three days previously with D-amphetamine compared to rats treated three days previously with saline. This increase in the expression of Fos-like immunoreactivity in rat striatum was characterized by a significantly greater number of immunoreactive nuclei and a significant increase in the intensity of the immunoreactivity. This sensitization of c-fos expression following a repeated administration of D-amphetamine indicates an increased activation of post-synaptic elements in rat striatum. PMID- 8453469 TI - Developmental abnormalities of corticospinal tract neurons in prenatally irradiated rats: a study using retrograde labeling with Fast blue and intracellular Lucifer yellow staining. AB - The effect of prenatal X-irradiation on the ontogenesis of corticospinal tract (CST) neurons was examined in rats using retrograde labeling with Fast blue and intracellular Lucifer yellow staining. In prenatally irradiated rats, the cortical laminar architecture of the CST neurons was confused and many cells demonstrated migratory disturbances. Migratory-disordered CST neurons at deeper cortical levels resembled pyramidal cells, but their apical dendrites were oriented in various directions and the development of their dendrites was poor. Migratory-disordered CST neurons near the ependymal layer demonstrated round somata and many thin dendrites with spokewise radiation, suggesting a maturation disturbance. These results suggested that prenatal X-irradiation impeded the migration and maturation of CST neurons. These findings may form the basis for analyzing the mechanisms of radiation-induced mental retardation and behavioral changes. PMID- 8453470 TI - Antinociceptive activity of liposome-entrapped calcitonin by systemic administration in mice. AB - Porcine calcitonin (pCT) encapsulated in sulfatide-containing reverse-phase evaporation vesicles (REVs) was shown to induce long-lasting and dose-dependent antinociceptive effect by systemic injection in mice. Its antinociceptive activity is found to be dependent on the route of administration. In contrast, neither unencapsulated pCT nor pCT encapsulated in sulfatide-free REVs was effective. These results suggest that pCT entrapped in sulfatide-containing liposomes might be able to cross the blood-brain barrier (BBB) and to produce central antinociception in mice. PMID- 8453471 TI - Effect of embryonic hippocampal transplantation in amygdaloid kindled rat. AB - Embryonic neural tissue was transplanted into previously kindled rats. A thirteen to fourteen-day embryonic hippocampal cell suspension was grafted in the stratum oriens near the CA2 area of the hippocampus. Almost 80% of the animals had a good recovery and became seizure-free. Injection of neocortical cells or saline did not show any positive effect on the kindling susceptibility. Although 20 day embryonic cell transplantation was also effective, the effect did not last as long as the 13- to 14-day embryonic transplantation. These observations open the possibility that the neural grafts may be used for therapy of medically intractable epilepsies. PMID- 8453472 TI - Neuropeptide Y-immunoreactive terminals form axo-axonic synaptic arrangements in the substantia gelatinosa (lamina II) of the cat spinal dorsal horn. AB - The ultrastructural organization of nerve terminals containing neuropeptide Y immunoreactivity was studied in the substantia gelatinosa of the cat spinal dorsal horn. Seventy immunoreactive boutons were examined through serial sections and 67 of them were found to form between one and five synaptic junctions with dendrites (59.5% of synapses), somata (3% of synapses) and other axon terminals (37.5% of synapses). The postsynaptic axon terminals were often the central boutons of glomeruli. These findings suggest that neuropeptide Y regulates spinal sensory transmission through both a postsynaptic action upon dorsal horn neurons and a presynaptic action upon primary afferent terminals. PMID- 8453473 TI - Localization of NADPH diaphorase in neurons of the rostral ventral medulla: possible role of nitric oxide in central autonomic regulation and oxygen chemoreception. AB - We studied whether neurons containing nitric oxide synthase (NOS) are localized to the rostral ventrolateral medulla (RVM) and, if so, whether they are distinct from the adrenergic neurons of the C1 group. NOS-containing neurons and/or C1 neurons were visualized using NADPH diaphorase histochemistry and phenylethanolamine N-methyltransferase (PNMT) immunohistochemistry, respectively. A column of NADPH diaphorase-positive neurons, extending 2 mm in the rostrocaudal plane, was observed lateral to the inferior olive and medial to the C1 neurons. Double labelling studies showed that NADPH diaphorase-positive neurons were not immunoreactive for PNMT, indicating that the two enzymes were localized in the different cells. Furthermore, only a small fraction of NADPH diaphorase neurons were retrogradely labelled after injections of fluorogold into the thoracic cord. We conclude that the RVM contains a well-defined group of neurons endowed with NOS that are distinct from the adrenergic neurons of the C1 group and have only limited monosynaptic projections to the spinal cord. Since the RVM is involved in the control of arterial pressure and in oxygen-conserving reflexes, the findings raise the possibility that nitric oxide participates in central autonomic regulation and oxygen chemoreception. PMID- 8453474 TI - Blockade of behavioral sensitization to cocaine and amphetamine by inhibitors of protein synthesis. AB - Anisomycin and cycloheximide were used to investigate the role of protein synthesis in the mechanism of behavioral sensitization to the stereotypic effects of cocaine and amphetamine in mice. The drugs completely antagonize induction and partially block expression of the sensitization. Because these drugs were found to be neither antidopaminergic nor antiglutamatergic, it seems that they disrupt sensitization at a novel locus. The antagonism of expression is limited to that quantitative fraction of the response derived from the sensitization reaction; the acute response is unaffected by the inhibitors of protein synthesis. The results differ from those obtained with haloperidol which can completely block either the acute or sensitized response to the stimulants. These results suggest that the sensitized response is functionally different from that of the acute response. The blockage of sensitization induction by the protein synthesis inhibitors may be related to other reports that the stimulants induce the transcription of immediate early genes; however, the relationship between the activation of immediate early genes and behavioral sensitization remains to be determined. PMID- 8453475 TI - Morphometric effects of intermittent kindled seizures and limbic status epilepticus in the dentate gyrus of the rat. AB - The effect of recurrent seizures on the hippocampus has been controversial for many years. To determine the effect different seizure paradigms had on the structure of the dentate gyrus, we conducted histological studies on the dentate gyrus (DG) from three groups of rats: (1) those that had experienced 1500 intermittent kindled seizures; (2) those that had experienced a single episode of limbic status epilepticus (SE); and (3) control rats that had been implanted with electrodes. When compared to controls the DG of SE rats was overall slightly, but non-significantly, smaller, but the DG of rats with 1500 kindled seizures was significantly larger. The decrease of size following SE was attributable to a significant atrophy of the molecular layer. The increase in area associated with kindling was the result of an enlargement of the molecular layer and the hilus. Absolute neuronal counts showed a decrease in the hilus after SE but no change following kindling, but both groups had decreased neuronal densities in the hilus when compared to controls. The decreased density after SE was secondary to neuronal loss, but the decrease in neuronal density following kindling was the result of the expansion of the hilar neuropil without change in the number of neurons. This study extends our previous findings in Ammon's horn and indicates that SE induces significant neuronal loss, but numerous intermittent kindled seizures have no effect on neuronal numbers in the DG. PMID- 8453476 TI - Variation in the expression of c-fos after intoxication by soman. Comparative study using in situ hybridization and immunohistochemistry. AB - A massive and transitory increase in c-fos mRNA and Fos protein occurred in rats intoxicated by a single dose of soman (organophosphate compound and irreversible cholinesterase inhibitor) only in animals that had seizures. Comparison of immunohistochemistry that localizes Fos protein and of in situ hybridization that localizes its mRNA showed that there was an early and explosive expression of mRNA in many cerebral regions followed by transitory immunoreactivity in only some regions (piriform cortex, entorhinal area, hippocampus). The levels of mRNA and c-fos-like immunoreactivity decreased slowly and returned to basal level 24 h after soman administration. PMID- 8453477 TI - Dose-dependent effects of D-N-allylnormetazocine on regional cerebral metabolic rates for glucose. AB - Cerebral metabolic patterns produced by different doses of the benzomorphan opioid drug, D-N-allylnormetazocine (D-NANM), were studied using the 2-deoxy-D-[1 14C]glucose method in rats. The lowest dose of D-NANM (0.5 mg/kg) decreased regional cerebral metabolic rates for glucose (rCMRglc) in areas, such as cranial nerve nuclei, that contain high densities of sigma (sigma) receptors. However, higher doses of the drug (2.7 and 5 mg/kg) increased rCMRglc in components of the extrapyramidal motor and limbic systems. Some of these latter areas (e.g. molecular layer of the dentate gyrus, accumbens nucleus, globus pallidus, ventral posterior nucleus of the thalamus) are not enriched in sigma receptors. Reductions in rCMRglc produced by the lowest dose of D-NANM probably reflect direct interactions of the drug with sigma receptors, whereas increases in rCMRglc observed with the highest doses more likely result from effects of D-NANM on PCP receptors. PMID- 8453478 TI - Functional role of brain AT1 and AT2 receptors in the central angiotensin II pressor response. AB - Intracerebroventricular (i.c.v.) angiotensin II (ANG II) increases vascular resistance and elicits a pressor response characterized by sympathetic nervous system activation (SNS component) and increased vasopressin (VP) secretion (VP component). This study examines the role of brain AT1 and AT2 ANG II receptors in mediating the pressor and renal hemodynamic effects of i.c.v. ANG II in conscious Sprague-Dawley rats. Mean arterial pressure, heart rate and renal vascular resistance responses to i.c.v. ANG II (100 ng in 5 microliters) were determined 10 min after i.c.v. injection of either the AT1 receptor antagonist, DuP 753 (1.0, 2.5, 5.0, 10.0 micrograms), the AT2 receptor ligand, PD 123319 (3.5 x [10( 6), 10(-4), 10(-2), 10(0)] micrograms), or both. In control rats, i.c.v. DuP 753 prevented the pressor response and the increase in renal vascular resistance that occurred following i.c.v. ANG II in a dose-dependent manner (P < 0.05), while i.c.v. PD 123319 was without affect. When the VP- and SNS components were studied individually, by preventing the SNS component with intravenous (i.v.) chlorisondamine or the VP component with a V1 receptor antagonist (i.v.) similar results were obtained; DuP 753 prevented the SNS component and significantly reduced the VP component. These results indicate that both central ANG II pressor components are mediated primarily by brain AT1 receptors. However, doses of DuP 753 were more effective when combined with 3.5 micrograms of PD 123319 than when given alone (P < 0.05), suggesting that the pressor effects of i.c.v. ANG II may involve activation of multiple ANG II receptor subtypes. PMID- 8453479 TI - Identity of the dorsal hippocampal region most vulnerable to cerebral ischemia. AB - Our previous investigations demonstrated that neurons in the area between the subiculum and the medial CA1 region and another area between the lateral CA1 and the CA3 region of the hippocampus are very vulnerable to cerebral ischemia in gerbils, where irreversible damages have been observed occur as early as 4-5 min after unilateral or bilateral common carotid artery occlusion. The present study was aimed to characterize these areas anatomically by using the immunohistochemical and zinc histochemical as well as Golgi silver impregnation methods. Our results indicated that these two areas which are topographically apart on the coronal section actually had a common origin in the rostral part of the hippocampus and that they were separated by insertion of the Ca1 neurons between them in the more caudal part of the hippocampus. The distribution pattern of mossy fibers indicated that these areas belonged to the CA2 region. The double immunohistochemical and zinc histochemical procedure confirmed that these areas developed ischemic lesions promptly even without reperfusion but that the CA1 region did not develop similar lesions until after reperfusion for 12-24 h if the ischemic period was brief. While the reason for the observed susceptibility of the CA2 region is not certain at the present time, it is important to distinguish the ischemic lesions in the CA2 region from those in the CA1 and CA3 regions. PMID- 8453480 TI - Contralateral inhibition of soleus H reflexes with different velocities of passive movement of the opposite leg. AB - The research question was, do events arising from rhythmic passive movement of the human leg lead to inhibition of the H reflex pathway in the stationary leg contralateral to that movement? Further, as the angular velocity of the passive movement increases, does the contralateral reflex inhibition also increase? Stable stimulation of the tibial nerve elicited H reflexes in the EMG of soleus. Trials involved the stimulated or the contralateral leg being rotated passively in a pedalling motion, at various velocities. The controls were made with the subjects seated and relaxed. The results showed that reflex magnitudes were significantly depressed when the test limb was passively rotated at 60 rpm. in comparison to the seated control trials. Rotation of the opposite limb depressed reflex magnitudes in the test limb, which was stationary. This contralateral inhibition increased, (mean reflex magnitudes of 62.68%, 41.04%, 16.65% and 9.58% of peak-to-peak Mmax), as the velocity of rotation of the opposite limb increased (10, 30, 60, 90 rpm, respectively) (P < 0.01). The effect of movement velocity was interpreted as the result of altered sensory receptor discharge arising from the passive movement. It is concluded that contralateral sensory activity contributes to the movement-elicited afferent discharge which tunes the spinal somatosensory-motor mechanisms for human locomotion. PMID- 8453481 TI - Enhancement of water intake in rats after lidocaine injection in the zona incerta. AB - Physiological evidence indicates that the zona incerta (ZI) may be an important region for convergence of signals mediating drinking. It is known that the ZI receives neural influences from brain osmoreceptive zones. Also there are wide spread projections from the ZI to the neocortex. In the present experiments, lidocaine (1 microliter, 20 ng/microliters) was injected into the rostral aspect of the ZI. The animals were previously stimulated for water drinking by: a) overnight water deprivation; b) 2 M NaCl IP; c) AII (50 ng) in the anteroventral wall of the third ventricle (AV3V). In every case, lidocaine administration significantly enhanced the volume of water drank. The results support the idea that ZI exerts an inhibitory influence upon the expression of drinking behavior. PMID- 8453482 TI - Use of a clinical MR scanner for imaging the rat brain. AB - Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy are established techniques that enable noninvasive anatomic and functional tissue characterization in vivo. These tools have been employed to probe experimental models of neoplasia, cerebrovascular disease, brain injury, and neurotransplantation in small animals. To date, these studies have been executed primarily on research-dedicated instruments of limited availability or resolution. Using relatively straightforward software and hardware modifications of a widely used clinical MRI unit, we were able to image numerous structures within the living rat brain including the neostriatum, hippocampus, periaqueductal gray, and the ventricular system. Illustrative applications of this imaging technique in two intracerebral infusion models involving rats are presented. Such adaptation of clinical MRI scanners has the potential to significantly expand the availability of high resolution in vivo imaging of small animals for a variety of experimental protocols. PMID- 8453483 TI - Food and water intake responses of the domestic fowl to norepinephrine infusion at circumscribed neural sites. AB - The effect on food and water intake of injection of norepinephrine into circumscribed brain sites of the domestic fowl was investigated. Injection of norepinephrine into sites throughout the preoptic area caused reliable increases in food intake. Food intake was also increased by injection of norepinephrine in the ventromedial nucleus, paraventricular nucleus, and medial septal sites. Food intake was decreased by injections near the lateral septal organ and the anterior portion of both the nucleus reticularis superior, pars dorsalis, and the tractus occipitomesencephalicus. Within the preoptic area, water intake was increased at basolateral sites but was inconsistently affected at more medial sites. No consistent trends were noted at sites examined outside the preoptic-hypothalamic area. PMID- 8453484 TI - Lateral preoptic neurons inhibit thirst in the rat. AB - Kainic acid (KA) and muscimol were injected into the lateral preoptic area (LPO) of the rat to study their effects on drinking behavior. A low dose (5 ng) of KA, which stimulates neurons, decreased the amount of water intake induced by hypertonic saline (IP) and angiotensin II (SC). Injection of 2 ng muscimol, a potent GABAA receptor agonist that suppresses neurons, facilitated drinking responses induced by hypertonic saline, but did not affect angiotensin II-induced drinking. Rats injected with a high dose (150 ng) of KA, which destroys neurons, showed marked polydipsia accompanied by increased urination. One week after the KA lesion, drinking and urine output recovered to normal. During the polydipsia, a small volume of concentrated urine could be excreted if water intake was restricted. After recovery, excessive drinking responses followed water deprivation and hypertonic saline load. The rats normally drank water in response to angiotensin II and to polyethylene glycol solution. The results show that activation of LPO neurons inhibits water intake, and that suppression of LPO neurons facilitates osmotically induced water intake. Therefore, LPO neurons are probably involved in the inhibition of thirst. PMID- 8453485 TI - Gangliosides facilitate the recovery of behavioral response mediated by dopaminergic sites following their irreversible blockade. AB - The effect of acute and chronic exogenous ganglioside (G) administration on the functional recovery of dopaminergic receptors following their blockade by N ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) was investigated by means of apomorphine (APO)-induced stereotyped behavior. Animals previously treated with EEDQ exhibited a lack of behavioral response to APO 6 or 24 h later. A progressive behavioral recovery was already evident at day 3 and reached control values at day 7. G pretreatment accelerated the behavioral recovery after EEDQ administration, because a higher behavioral response to APO in these animals as compared with rats treated with EEDQ alone at the same time was observed. These findings indicate that G accelerates the functional recovery of dopaminergic sites following their irreversible blockade. PMID- 8453486 TI - The internal organization of the human solitary nucleus. AB - The present study examines the topography and cytoarchitecture of the solitary nucleus (Sol). Three human medulla oblongatae were serially sectioned and alternate sections were reacted for the enzyme acetylcholinesterase or stained with cresyl violet. The 10 component subnuclei of Sol were identified on the basis of their acetylcholinesterase reactivity and cytoarchitecture. These subnuclei are the paracommissural, commissural, gelatinosus, medial, ventral, ventrolateral, dorsal, dorsolateral, intermediate, and interstitial. Cytoarchitecturally, Sol is characterised by an abundance of small cells of varied morphology but also features some medium to large cells as well as pigmented neurons which are differentially distributed across the subnuclei. From spaced serial sections, the outlines of the subnuclei and the entire Sol were used to create three-dimensional computer reconstructions to display the position and extent of each component subnucleus. Our results show that the internal architecture of the human solitary nucleus is similar to that of rodents and carnivores, though there are some notable species differences. PMID- 8453487 TI - Neurite outgrowth from N18TG2 neuroblastoma induced by H-7, a protein kinase inhibitor, in the presence of colchicine. AB - Our previous studies have demonstrated that the protein kinase inhibitor H-7 promotes neurite outgrowth from mouse neuroblastoma N18TG2 cells as well as from primary cerebellar cells, and also that the neurites induced by H-7 were more tolerant of colchicine (COL) than those induced by dibutyryl cAMP (dB-cAMP). In the present study, we tested the effects of H-7 and dB-cAMP on neurite growth from N18TG2 cells in the presence of COL. We found that only H-7 promoted neurite formation in the presence of COL. The percentage of cells with neurites induced by H-7 in the presence of COL (H-7 + COL) was similar to that induced by H-7 alone. The neurites induced by H-7 + COL grew straight. They were very thin (less than 1 micron in diameter) and had round varicosities, as did the neurites induced by H-7 alone. By transmission electron microscopy, the neurites induced by H-7 + COL were found to contain longitudinally arranged intermediate filaments (IF). Microtubules (MT) were not observed within the neurites. We also examined the effect of cytochalasin B (CB) on the neurites induced by H-7 + COL and by H-7 alone. The neurites induced by H-7 + COL were tolerant to CB, but those induced by H-7 were resorbed completely within 24 h after CB was applied. Neurites tolerant to CB contained longitudinally IF. Simultaneous application of CB with H 7 + COL or with H-7 alone did not induce neurite formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8453488 TI - A re-evaluation of the effects of gonadal steroids on neuronal activity in the male rat. AB - Single unit activity (SUA) was recorded from 77 cells located in the arcuate nucleus (ARC) and medial preoptic area (MPA) of anesthetized, intact male rats. Animals were administered vehicle, testosterone (T; 5 or 50 micrograms) or 17 beta-estradiol (E; 0.5 microgram) intravenously and SUA was monitored for 8-12 min. T (50 micrograms) reduced SUA in 50% of ARC units and 44% of MPA units within 2.1 +/- 0.46 and 3.3 +/- 0.92 min, respectively. Inhibition of ARC SUA was more pronounced than MPA SUA. A small percentage (9%) of ARC units were excited by T. E reduced SUA in 29% of ARC units and 27% of MPA units. Single doses of 5 micrograms T did not affect ARC activity. However, when followed within 10 min by an additional dose of 5 or 50 micrograms T, 30% and 43% of ARC units were inhibited, respectively. Doses (10 micrograms) of T produced plasma T concentrations within physiological limits, although 50 micrograms doses produced supraphysiological T levels. Neither dose affected circulating LH concentrations. We conclude that physiological and supraphysiological concentrations of T can rapidly affect SUA within the ARC. PMID- 8453489 TI - Actin distribution along the lateral wall of gerbil outer hair cells. AB - Outer hair cells can contract parallel to their long axis, and it has been hypothesized that actin may play a role in this contraction. In this study, actin distribution was examined in the gerbil organ of Corti using postembedment immunoelectron microscopy. In addition to regions typically labelled by actin antibodies and observed by epifluorescence--the cuticular plate, stereocilia, and supporting cell processes--these procedures preserved the ultrastructure of the cell and allowed us to demonstrate actin reactivity along the lateral wall of the outer hair cells between the subsurface cisterns and the plasma membrane. This region is the location of structures (pillars and cortical cytoskeleton) though to be associated with contraction of the outer hair cells. PMID- 8453490 TI - The hypothalamic aggression region of the rat: observations on the synaptic organization. AB - Comparison of detailed physiological and morphological data shows that the hypothalamic aggression region in the rat largely coincides with the intermediate hypothalamic area. This region has a neuronal density of about 35.10(3) neurons per mm3, a synaptic density of about 300.10(6) per mm3, and a synapse to neuron ratio of about 9000, including only about 200 axosomatic synaptic contacts per neuron. Septal synaptic contacts in this region originate from unmyelinated axons and are axodendritic of the asymmetrical type, with an average bouton diameter of 785 nm and an average synaptic contact length of 270 nm. PMID- 8453491 TI - Intraocular injection of APB decreases the metabolic response of the rat superior colliculus. AB - The functional activity of the superior colliculus (SC) following flash stimulation was examined by means of 2-deoxyglucose (2DG) method in monocularly enucleated Long-Evans rats intraocularly injected with a solution of 2-amino-4 phosphonobutyric acid (APB), able to silence the ON retinal activity. After APB injection SC layers recipient of retinal axons suffered a sustained 2DG decrease as compared to controls. Moreover, whereas glucose utilization in normal rat SC appears unevenly distributed and closely related to retinal axon density, by contrast, APB-treated rats showed a rather uniform metabolic activity throughout the SC surface. Furthermore, we calculated the 2DG uptake percentage reduction in 12 SC loci of APB rats in respect to homologous loci of controls: glucose utilization decreases at the loci largely differ from each other, showing that retinal axons carrying ON activity are dispersed over the SC in a mosaic pattern. Thus, the SC metabolic map should be representative of its retinotopic organization which, in turn, depends on the asymmetric distribution in the rat's retina of W-like as well as of other ganglion cell types. PMID- 8453492 TI - Evidence for the involvement of serotonin in acute stress-induced release of luteinizing hormone in the male rat. AB - The influence of serotonin on luteinizing hormone (LH) release caused by exposure to two acute stressors differing in their intensity (restraint in tubes and immobilization in woodboards) was studied in adult male rats. Inhibition of serotonin synthesis with p-chlorophenylalanine (PCPA) significantly abolished LH release caused by immobilization (IMO). Administration of the serotonin antagonists mianserine and methiothepin also eliminated LH release caused by IMO without altering basal LH levels. These data represent the first evidence that a classical neurotransmitter (serotonin) is involved in LH release caused by stress in the rat. PMID- 8453493 TI - Differential sleep modulation by sequentially administered muramyl dipeptide and uridine. AB - In an attempt to investigate the effects on sleep modulation of order of administration of two substances, sequential intracerebroventricular (ICV) infusions of muramyl dipeptide (MDP, 1.0 nmol) and uridine (5.0 pmol) were conducted in freely behaving rats. To eliminate the influence of intermittent infusions on their behavior, the rats were continuously ICV infused with physiological saline solution, which did not affect their normal sleep-waking dynamics. Under these experimental conditions, uridine infusion (2400-0500 h) attenuated the enhancement of slow-wave sleep (SWS) caused by prior infusion of MDP (1900-2400 h) to the baseline level and, thus, did not exert a sleep promoting property. In contrast, MDP infusion (2400-0500 h) further potentiated the SWS-enhancing activity of preinfused uridine (1900-2400 h). A single infusion of MDP or uridine (2400-0500 h) similarly enhanced SWS. These results demonstrate that observed differences in the induction and maintenance of sleep are dependent upon the order of exogenously infused uridine and MDP. The time sequence per se of these sleep substances may be responsible for the differential temporal changes in sleep. It is, therefore, assumed that a crucial order of multiple sleep substances may dynamically and differentially regulate sleep in the brain. PMID- 8453494 TI - Dexfenfluramine induces Fos-like immunoreactivity in discrete brain regions in rats. AB - Administration of the anorectic agent, dexfenfluramine (DFEN) to rats induced dose- and time-dependent expression of Fos-like immunoreactivity in several discrete brain regions of rats. At moderate doses, the regions showing the most intense Fos immunostaining included the bed nucleus of the stria terminalis, the lateral part of the central amygdala, midline thalamic nuclei, habenular nuclei, lateral parabrachial nucleus, and nucleus of the solitary tract. It is suggested that these nuclei, many of which are known to receive gustatory or visceral input, may form part of a functional circuit via which DFEN modulates food intake. Rats that were made hungry by either food deprivation or administration of insulin also showed induction of Fos in several brain regions, but only that in the supramamillary/ventral tegmental area was suppressed by pretreatment with an anorectic dose of DFEN. The functional significance of these sites requires further investigation. PMID- 8453495 TI - Basal forebrain and frontal cortex neuron responses during visual discrimination in the rat. AB - Using a classical conditioning procedure in urethane-anesthetized rats, a light applied to one eye (CS+) was paired with medial forebrain bundle (MFB) stimulation, whereas a light applied to the other eye (CS-) was not paired. Basal forebrain neurons in the substantia innominata, medial globus pallidus, and nucleus basalis magnocellularis responded differentially to CS+ and CS-, with larger responses to CS+. Some neurons were excited by CS+, and others were inhibited. Fifty percent of these neurons responded in the same direction to CS+ and MFB stimulation, and 38% responded in opposite directions. Frontal cortex neurons exhibited similar differential responses; 47% of the differential responses to CS+ were in the same direction as the response to MFB stimulation, and 29% were in the opposite direction. When light to either eye was paired with MFB stimulation, conditioning-related basal forebrain neuron responses of comparable magnitude to left and right eye illumination were observed, providing evidence that association of CS and UCS rather than the eye to which light was applied determined the differential response to CS+. Also, two different intensities of light induced comparable basal forebrain responses when both were paired with the UCS. These experiments provide support for a role of the basal forebrain in conditioning-related neural activity. Furthermore, this preparation can be utilized to investigate transmitter systems that mediate conditioning related responses of basal forebrain neurons. PMID- 8453496 TI - Sequential alteration of [3H]rolipram binding in gerbil brain after transient cerebral ischemia. AB - The time course of rolipram (Ca2+/calmodulin independent cyclic adenosine monophosphate inhibitor) binding sites changes following gerbil transient forebrain ischemia was determined using receptor autoradiography. Gerbils subjected to 10-min ischemia revealed a significant reduction in rolipram binding in most selectively vulnerable regions early in the recirculation (1-5 h). Marked reduction in the rolipram binding was seen in the selectively vulnerable areas 48 h or 7 days after ischemia. Thereafter, the rolipram binding in the hippocampal CA1 and CA3 sectors, which were most vulnerable to ischemia, was severely reduced up to 1 month after recirculation. In contrast, the reduction of the rolipram binding activity in other regions recovered to sham-operated level or showed a slight recovery. Interestingly, the dentate gyrus, which was resistant to ischemia, also exhibited a significant reduction of the rolipram binding activity up to 1 month after ischemia. Eight months after ischemia, the hippocampal CA1 and CA3 sectors showed severe shrinkage and marked reduction in the rolipram binding. Other regions exhibited no significant reduction in the rolipram binding except for a slight reduction in the thalamus. These results demonstrate that transient cerebral ischemia causes severe reduction in rolipram binding sites in selectively vulnerable areas, and this reduction precedes the neuronal cell loss. These findings may reflect the alteration of an intracellular phosphodiesterase activity after ischemia. PMID- 8453497 TI - Metabolic changes during and after transient clamping of carotid arteries in normotensive rats. AB - In the present experiments changes of local metabolism in the striatum, hippocampus, and frontal cortex during and after transient clamping of carotid arteries in normotensive rats (BCCA) were studied by continuous measurement of local cerebral temperature, partial oxygen tension (PO2), and extracellular levels of lactate. Local temperature in the striatum, hippocampus, and frontal cortex fell between 1.7 and 2.3 degrees C upon occlusion and quickly returned to preocclusion values after free flow had been established. Local PO2 was reduced in the striatum, hippocampus, and frontal cortex to values between 70 and 30% during BCCA. Immediately after termination of BCCA the PO2 showed a tendency to recover in the striatum and frontal cortex, whereas in the hippocampus, this process started later. Extracellular levels of lactate within these three structures increased during BCCA and went down to preocclusion values within the observed period of reperfusion. The results suggest that BCCA induces a transient anaerobic metabolism that seems to be sufficient to evoke functional changes without neuronal damage. PMID- 8453498 TI - A model of human sleep homeostasis based on EEG slow-wave activity: quantitative comparison of data and simulations. AB - EEG slow-wave activity (SWA; spectral power in the 0.75-4.5 Hz band) is a function of the duration of prior waking and, thereby, an indicator of sleep homeostasis. We present a model that accounts for both the declining trend of SWA during sleep and for its variation within the successive nonrapid eye movement (non-REM) sleep episodes. The values of the model parameters were estimated by an optimization procedure in which empirical SWA of baseline nights (16 subjects, 26 nights) served as a reference. A sensitivity analysis revealed the model to be quite robust to small changes (+/- 5%) of the parameter values. The estimated parameter values were used to simulate data sets from three different experimental protocols (sleep in the evening or sleep in the morning after prolonged waking, or extended sleep initiated at the habitual bedtime; n = 8 or 9). The timing of the REM trigger parameter was derived from the empirical data. A close fit was obtained between the simulated and empirical SWA data, and even the occasional late SWA peaks during extended sleep could be reproduced. Minor discrepancies suggest indirect or direct circadian influences on SWA. The simulations demonstrate that the concept of sleep homeostasis as proposed in the two-process model of sleep regulation can be refined to account in quantitative terms for empirical data and to predict the changes induced by the prolongation of waking or sleep. PMID- 8453499 TI - Suggested fundamental concepts in skeletal physiology. PMID- 8453500 TI - Temporal variations in iliac trabecular bone formation in vertebral osteoporosis. AB - The histologic heterogeneity of osteoporosis relative to normal controls has attracted great interest. There has been controversy as to whether patients with high turnover osteoporosis may convert to a normal or low turnover form, and vice versa. We have studied 44 patients over 12 years by dynamic histomorphometry and 85Sr kinetics+calcium balance performed within 60 days in 20 patients (Group 1) and 75-808 days apart in the remainder (Group 2). In the first group, the histologic tissue level bone formation rate (BFR/BV or BFR/BS) was predictive of the 85Sr measurements of bone formation (r = 0.66 P < 0.01). There was no statistically significant correlation in Group 2 and the regression coefficients were significantly different (P = 0.01). Periodic regression was used to determine if seasonal changes were responsible for this loss of correlation; none was found that was of statistical significance. No systematic changes with time in bone formation were found in Group 2 during the period of observation; nor were consistent secular changes detected when the data for both groups were examined according to procedure date. In conclusion, bone formation may change with time in postmenopausal osteoporosis. Evidence that these changes are systematic was not found and this has implications for the design of treatment studies. PMID- 8453501 TI - Osteoclast recruitment in mice is stimulated by (3-amino-1-hydroxypropylidene) 1,1-bisphosphonate. AB - Though some evidence suggests that bisphosphonates (BPs) act directly on osteoclasts to inhibit bone resorption, other evidence suggests that they inhibit the development of the osteoclast. We found an increase in osteoclast recruitment in 2-day-old mice given (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD). A threefold increase in 5-bromo-2'-deoxyuridine (BrdU)-labeled osteoclast nuclei was observed on mouse parietal bones 3 days after APD injection. This suggests that inhibition of osteoclast development is not an action of APD in mice of this age. The mechanism of the increased recruitment was investigated. As osteoclast progenitors were not detected on parietal bones in vitro, we looked for an increase in circulating monocytes to account for the recruitment. No such increase was found, but when 51Cr-labeled bone marrow was injected intraperitoneally into mice given APD there was an increase in accumulation of 51Cr in calvaria and in femur and tibia over controls. This increase did not occur when 51Cr-labeled erythrocytes or free 51Cr was injected. We conclude that APD causes increased recruitment of osteoclast precursors by increasing the avidity of bone for hematopoietically derived cells. PMID- 8453502 TI - Cortical bone mass, composition, and mechanical properties in female rats in relation to age, long-term ovariectomy, and estrogen substitution. AB - The study comprised 12 groups of female rats: 6 groups of intact rats killed at 2, 6, 9, 12, 15, and 24 months of age, 4 groups of rats ovariectomized at 6 months and killed together with the intact rats at 9, 12, 15, and 24 months of age, and 2 groups of rats (one intact and one ovariectomized) treated with estrogen (2 micrograms estradiol valerate/rat/week s.c.) for 8 months before they were killed at 24 months of age. The composition, dimensions, and mechanical strength of intact bone and bone collagen from femoral diaphyses were investigated in relation to age, ovariectomy, and estrogen administration. Up to 6-9 months of age, the axial length, percentage ash, density, and compressive mechanical stress increased, whereas percentage collagen decreased. An age related increase in bone mass, cross-sectional area, and wall thickness and a decrease in mechanical quality of bone collagen were apparent from 2 to 24 months of age. An age-related periosteal bone formation and the absence of endosteal bone resorption were demonstrated in intact rats. Compared with intact rats, ovariectomy was followed by an increase in body weight, a tendency to reduced percentage ash and a depressed bone mass, cross-sectional area, and wall thickness of femoral diaphyses. The compressive mechanical stress of intact bone and the mechanical quality of bone collagen were unaffected by ovariectomy. Ovariectomy did not influence the periosteal bone formation but induced an endosteal bone resorption not present in the intact rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8453503 TI - Culture and differentiation of chondrocytes entrapped in alginate gels. AB - We studied the response to culture conditions and the differentiative ability in suspension culture in alginate gels of resting chondrocytes from the preosseous cartilage of adult pig scapula. It was found that the maximum rate of chondrocyte duplication is reached at the fourth day in culture whereas the rate of proteoglycan synthesis and alkaline phosphatase expression do not gain a maximum value before the seventh day. During the culture time, the chondrocytes undergo differentiation as it is demonstrated by the alkaline phosphatase specific activity increase and by morphological criteria (hypertrophy, increase of the number of mitochondria per cell, increased endoplasmic reticulum, matrix vesicle production). The alginate gels can be easily dissolved to obtain cell populations in which the variation of cytosolic calcium concentration following a proliferative stimulus can be conveniently observed using the conventional procedure of Fura 2. PMID- 8453504 TI - Reduced mechanical competence of bone by ovariectomy and its preservation with 24R,25-dihydroxyvitamin D3 administration in beagles. AB - To examine changes in mechanical competence of bone caused by ovariectomy, and to assess the effect of 24R,25-dihydroxyvitamin D3 (24R,25(OH)2D3) administration on mass and structure, we conducted mechanical tests on canine lumbar vertebrae and femur 31 months after surgery. Beagles weighing 9-10 kg were ovariectomized (OVX) or sham operated (n = 3, group 1). OVX dogs were divided into three groups. Group 2 (n = 3) received only the agent vehicle, groups 3 (n = 4) and 4 (n = 4) received daily 24R,25(OH)2D3 doses of 2 and 10 mcg/kg, respectively from 1 month after surgery. In group 4, the dose level was increased up to 100 mcg/kg by the 17 month. Then, L3 and L4 vertebrae and left femur were excised from each animal. Torsional tests at the femoral diaphysis were conducted. On the L3 specimen, the circumferential shell was removed to obtain a cancellous core specimen. The shell was left intact on the L4 specimen. In compression tests, the loading was stopped just after maximal strength was reached for minimum specimen collapse, from which 7-mcm thick, undecalcified, midcross sections parallel to the base of the specimen were obtained. Neither femoral morphology, bone mineral contents (BMCs) nor structural stiffness indicated a significant difference among groups. Though L3 and L4 BMCs were reduced in group 2, in group 3 and 4 they were significantly larger than in group 2. Compression tests on lumbar vertebral specimens showed a significant decrease in mechanical parameters in group 2. On the cancellous core specimen of L3, the mean structural stiffness in group 2 was 31.8% of that in group 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8453505 TI - Differential effects of glucocorticoids on cortical appendicular and cortical vertebral bone mineral content. AB - The susceptibility to glucocorticoid-induced bone loss may vary in different parts of the skeleton. We studied 62 patients with rheumatoid arthritis, 26 of whom were on low-dose glucocorticoid treatment. Bone mineral content (BMC) in the forearm was measured by single photon absorptiometry at a cortical, diaphyseal, and at a mixed cortical and trabecular, metaphyseal site. Lumbar BMC was measured by dual energy computed tomography in a trabecular and a cortical region of interest. The presence of vertebral deformities was evaluated on lateral spine radiographs. After correction for possibly confounding variables, prednisone therapy significantly influenced BMC at both the trabecular (-22.0%, 95% confidence interval -36.0% to -8.1%) and cortical (-24.8%, 95% confidence interval -39.3% to -10.3%) lumbar site. A significant effect was also seen at the metaphyseal (-15.7%, 95% confidence interval -27.1% to -4.2%), but not the diaphyseal (-3.9%, 95% confidence interval -14.1% to 6.4%) site in the forearm. Correlations between peripheral and vertebral BMC were moderate at best. The diaphyseal to metaphyseal BMC ratio did not identify patients with vertebral osteoporosis. It is concluded that the anterior cortical rim of the vertebral body is more susceptible to the effects of glucocorticoids than the cortical bone in the forearm, and that measurements of trabecular and anterior cortical vertebral BMC are essential in the management of patients with possible glucocorticoid-associated osteoporosis. PMID- 8453506 TI - Increased bone growth by local prostaglandin E2 in rats. AB - The effects of prostaglandin E2 (PGE2) on bone growth were investigated in rats. Daily injection of PGE2 (1, 10, and 100 pmol) was given via local intraosseous route into the metaphysis of the left tibia for 14 days. The contralateral right tibia injected with vehicle and saline was for the control. The rats receiving no injection provided as normal control. The results obtained indicated that PGE2 slightly but significantly decreased the body weight increment without effect on tibial length. The most prominent effect of PGE2 was the increase of metaphyseal bone trabeculae by 45-81% in a dose-dependent manner. The microscopic examination revealed that PGE2 unequivocally increased the new woven bone formation. The bone cell population study showed no difference between the number of osteoblasts and osteoclasts in primary spongiosa of the PGE2-injected limbs and those of contralateral limbs. However, the numbers of osteoblasts and osteoclasts were markedly increased in secondary spongiosa in the PGE2-injected limbs. This finding confirmed a stimulatory role of PGE2 in the bone formation. The local intraosseous injection of PGE2 was proven to be a good model for the study of local growth factors on bone metabolism with a lower effective dose which eliminates the systemic side effects. PMID- 8453507 TI - Protein kinase C mediates flow-induced prostaglandin E2 production in osteoblasts. AB - Interstitial fluid flow generated by skeletal loading may be responsible for load induced bone remodeling. Production of prostaglandin E2 (PGE2), a potent mediator of bone remodeling, is augmented in osteoblasts exposed to fluid flow. Exposure to fluid flow resulted in a slight initial increase in PGE2 production (1-2 hour), followed by a dramatic increase (2-8 hours). The initial phase of only slightly increased PGE2 production was dependent on substrate availability. H7, a protein kinase C inhibitor, strongly inhibited flow-induced prostaglandin E2 production at all time points examined without effecting production in stationary cultures. Blocking protein synthesis with cycloheximide resulted in a 56% reduction in long-term flow-induced PGE2 production. Thus, the later phase appeared to be the result of an increased number of enzymes as well as increased activity of existing enzymes or increased substrate availability. In conclusion, fluid flow increases PGE2 production in osteoblasts via a protein kinase C dependent pathway involving de novo protein synthesis. PMID- 8453509 TI - A combination of calcitonin and bisphosphonate for the emergency treatment of severe tumor-induced hypercalcemia. PMID- 8453508 TI - Lack of association between free testosterone and bone density separate from age in elderly males. AB - It is unclear what proportion of the variance in bone density in elderly males is accounted for by testosterone status. We studied 112 ambulatory, elderly volunteers (mean age 71.7 years) and determined free testosterone (FT), as well as bone density measurements by photon absorptiometry at multiple sites. Our studies of 35 of these subjects 4 years later included morning FT and dual energy X-ray absorptiometry. There were no significant correlations between FT and bone density at multiple scanning sites with the effects of age partialed out. We suspect that our inability to detect a significant effect of FT on bone density was related to the relative strength of other determinants of bone density, as well as to the fact that FT values are far more dynamic than bone density. PMID- 8453510 TI - You'll learn or else! PMID- 8453511 TI - Radiographic surveys. PMID- 8453512 TI - Computer applications in the diagnosis and monitoring of periodontal disease. PMID- 8453513 TI - Quality service and a personal touch: redefining the "M" word. AB - Like it or not, dentistry is a service that patients (the consumers) may choose to reject. It's up to individual dentists to convince patients that their oral health should rank as a top priority. To achieve this goal, dental professionals must make a commitment to provide quality and personalized service. And this begins by developing and implementing a marketing strategy that defines and tracks patients' seemingly elusive needs. PMID- 8453514 TI - Adult dental health in the Keewatin. AB - In 1990, as part of a major health status assessment, a dental survey was carried out on a 20 per cent random sample of the adult population in the Keewatin region of the Northwest Territories. A 73 per cent response rate was obtained. Of the 397 people examined, 334 (88 per cent) identified themselves as Inuit. More than 20 per cent of the respondents were edentulous, including 10 per cent of those 18 to 34 years old. The median DMFT was 24 for all respondents and 21 for dentulous respondents. There was a significant difference between Inuit and non-Inuit respondents, which was most marked in the 18 to 34 year old age group (mean DMFT 22.1 versus 15.6, p < .001). The proportion of filled to decayed and filled surfaces (F/DF) was 50 per cent. Periodontal disease was common and increased with age. More than 73 per cent of the dentate individuals had gingival bleeding at one or more sites. Very few were free of calculus. Mean pocket depth increased with age (1.3 mm at 18-34 years of age, rising to 2.3 at 55 plus, p < .001). Sixty per cent of adults needed at least one restorative procedure, 68 per cent needed prophylaxis, and 45 per cent needed periodontal treatment. Men required more treatment of all types than women. The results of this study confirm the clinical impression that dental disease is rampant among the Inuit population. There are major needs for both preventive and treatment services.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8453515 TI - Indian and Inuit dental care in Canada: the past, the present, and the future. PMID- 8453516 TI - Tales of northern dentistry. PMID- 8453517 TI - Baffin Island--it's worth a visit. PMID- 8453518 TI - The enigma of amalgam in dentistry. PMID- 8453519 TI - Application of porcelain veneers following orthodontic treatment. AB - To date, porcelain laminate veneers have been used primarily to solve esthetic problems. As bonding materials and veneer restoration techniques have improved, however, functional demand has now been accepted. Porcelain laminate veneers have been applied to compensate for the limitations of orthodontic treatment. In order to allow optimum functional movement of the mandible, anterior and lateral guidances are required in the maxillary dentition. These guidances provide pathways for the opposing mandibular teeth. Anterior and canine guidances have been established by means of veneer placement, and no broken restorations have been observed in the past four years. When diastema spaces have recurred subsequent to orthodontic space closure, they have been restored with porcelain veneers so effectively that no relapse has been observed. This paper also examines instances where small lateral incisors have caused a discrepancy in the tooth size ratio between the upper and lower arches. Porcelain veneers were placed to harmonize the tooth size and to stabilize the occlusion. Relapse sometimes occurs after orthodontic tooth alignment. Over correction, therefore, is usually applied for rotated teeth, anterior deep or open bite, and Class II or III molar relationships. Some malocclusions, however, cannot be over corrected. For example, the spacing between the teeth, such as diastema, can easily reopen because it is impossible to apply over correction once space closure has been achieved. The same is true of lateral open bites, because occlusal contact cannot be corrected properly. In these cases, the patient must wear a retainer for longer than usual, and/or permanent splints must be used to stabilize the occlusion. Another causal factor of relapse is dysfunctional occlusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8453520 TI - Dental management of patients with sickle cell anemia. AB - Sickle cell anemia is endemic in certain parts of the world. With the increase in immigration into Canada from some of these areas, new demands are being placed on the country's health care system. However, improved methods of managing sickle cell anemia have resulted in a longer lifespan and better quality of life for patients afflicted with the disease. In most cases, these individuals can now remain out in the community for most of their lives, and are therefore likely to seek treatment from a neighborhood dentist. Consequently, dentists need to have an appreciation of sickle cell anemia and its implications for dental health. This article outlines the physiology, medical aspects, and dental manifestations of sickle cell anemia, and gives guidelines for its dental management. PMID- 8453522 TI - Bridge over changing times. PMID- 8453521 TI - A call to action. PMID- 8453523 TI - Overcoming computer phobia. PMID- 8453524 TI - Economics of the associate. PMID- 8453525 TI - Restrictive covenants--everything you wanted to know but were afraid to ask. AB - Principal/associate relationships are very common in dental practice today, and significant value is now associated with patient lists and practice locations. Therefore, principal dentists must take steps to protect valuable practice goodwill. The inclusion and proper use of restrictive covenants in associateship agreements should help to protect principal dentists. PMID- 8453526 TI - An associateship--"the beginning". AB - Associateships can be successful and profitable. However, prudent business principles must be followed by both parties. The relationship of two professionals is essentially different from other employee/employer situations, particularly so if the agenda of the principle practitioner is more complex. No matter what the level of complexity of the associate agreement, the will to agree based on full and complete disclosure is much more important than the adherence to some letter of the law. Most provisions of associate agreements are difficult, if not impossible, to enforce. Both sides are then at risk. The clearest form of protection is a complete and unreserved sharing of the requirements, expectations and intent of the relationship. PMID- 8453527 TI - Pediatric trauma and polyethylene reinforced composite fixed partial denture replacements: a new method. PMID- 8453529 TI - A macroeconomic review of dentistry in the 1980s. AB - Dental expenditures in Canada receive less attention than other expenditures in the health care sector. Using publicly-available records, the authors have shown that the overall expenditures on dental care rose from $1.3 billion to $3.1 billion during the 1980s, or from $54.35 per person to $117.78 per person. Inflation and population growth would account for about 64 per cent of the increase, and the balance ($650 million) would therefore result from more services being provided. Per capita dental expenditures by province and territory show that people in the territory purchase the least care ($33.01 per person in 1989) and those in British Columbia purchase the most care ($145.54 per person in 1989). Even though some costs are not included in the data sources used for this paper, the direct costs of preventing and treating dental diseases ranks third among all diseases or conditions, exceeded only by the costs related to cardiovascular diseases and mental disorders. PMID- 8453528 TI - Appropriate use of fluorides in the 1990s. PMID- 8453531 TI - Borderline personality disorder: building a new understanding. Hamilton, Ontario, January 24-25, 1991. Proceedings. PMID- 8453530 TI - A review of commonly prescribed oral antibiotics in general dentistry. AB - The microflora associated with odontogenic infections are typically mixed and of indigenous origin. Streptococcus, peptostreptococcus, peptococcus, fusobacterium, bacteroides, and actinomyces species are the principle microflora isolated from these infections. Penicillin V (phenoxymethyl penicillin) remains the antimicrobial of choice for the initial empirical treatment of odontogenic infections. This agent is safe, highly effective and inexpensive. Amoxicillin has little indication for the routine treatment of odontogenic infections. However, it is the agent of choice for endocarditis prophylaxis, as it produces higher serum levels than penicillin V. Erythromycin may be used for mild, acute odontogenic infections in penicillin-allergic patients. The high incidence of gastrointestinal disturbances and superinfection commonly associated with the ingestion of tetracycline limits its role in general dental practice. Tetracycline may be considered as an alternative therapy for penicillin-allergic patients over the age of 13 who cannot tolerate erythromycin. Clindamycin is very effective against all odontogenic pathogens, but its potential gastrointestinal toxicity relegates it to third- or even fourth-line therapy in general dentistry. Although metronidazole displays excellent activity against anaerobic gram negative bacilli, it is only moderately effective against facultative and anaerobic gram-positive cocci, and should not be used alone in the treatment of acute odontogenic infections. PMID- 8453532 TI - Biological markers in borderline personality disorder: new perspectives. AB - There has been much research on the biological markers of borderline personality disorder (BPD) in the last three years. The Dexamethasone Suppression Test, the Thyrotropin-Releasing Hormone Test and sleep studies no longer indicate that BPD is related to depression, although there is probably an affective subgroup. There may be evidence that some subgroups of BPD overlap with schizophrenia. An extensive analysis of serotonin studies provides exciting new directions for understanding suicidal, aggressive and especially impulsive traits. PMID- 8453533 TI - Borderline disorder and attachment pathology. AB - In this paper, the authors investigate the theoretical and empirical association between dysfunctions of the attachment system and borderline personality disorder. Attachment theory focuses on the maintenance of a sense of safety and security through a close personal relationship with a particular person. Based on a biological behavioural system, functional attachment relationships in adulthood rely on experiences and expectations of security within the relationship. These issues are also important to the definition and dynamics of borderline personality disorder. The dimensions and patterns of reciprocal attachment were compared with other scales measuring components of psychopathology and interpersonal relationships. In a sample of 85 female outpatients, only four of the attachment scales--feared loss, secure base, compulsive care-seeking and angry withdrawal--identified patients with high scores on a measure of borderline disorder. Of these four scales, feared loss had the predominant effect. These empirical results support the hypothesized relationship between dysfunctions of the attachment system and borderline disorder. PMID- 8453535 TI - The treatment of borderline personality disorder in light of the research on its long term outcome. AB - Studies of the long term outcome of borderline personality disorder have shown that, although most patients improve with time, there is a high rate of suicide associated with this disorder. In the absence of clinical trials which could demonstrate the long term effects of treatment, the management of the borderline patient must take into account the chronicity of the disorder. A wide range of treatment options are reviewed, all of which could be included in a model emphasizing continuous availability and intermittent active intervention. PMID- 8453534 TI - The assessment of ego development in borderline personality disorders. AB - The purpose of the study was to assess levels of ego functioning in a cohort of patients who met the criteria for borderline personality disorder. The Sentence Completion Test (SCT) and the Descriptions of Significant Others (DSO) test were used to measure dimensions of ego maturity. The borderline patients' responses on the SCT were compared with the responses of an outpatient sample of psychiatric patients and with general population norms established for the test. The scores on the SCT for a selected subgroup of five subjects were compared with their scores on the DSO. Contrary to expectation, the responses on the SCT by those with borderline personality disorder did not differ from those for the psychiatric outpatient sample or the general population norms. However the within group comparisons between the SCT and the DSO for the subgroup of five subjects showed comparable trends between tests. Discussion of the results focuses on the interpretations of the borderline patients' responses to the two tests. Emphasis is placed on the need to distinguish subsets of ego functions, which can be assessed separately using a variety of measurement strategies. PMID- 8453536 TI - Psychiatric rehabilitation model for borderline personality disorder. AB - Borderline personality disorder is a prevalent and chronic disorder characterized by significant morbidity and mortality. Limited success with current treatment approaches suggests that new models of treatment are needed. Aspects of the psychiatric rehabilitation model are applied to borderline personality disorder. This model has implications for the diagnosis and management of borderline personality disorder. The diagnosis of borderline personality disorder will be refined by characterizing the disabilities and handicaps that are associated with the disorder. The psychiatric rehabilitation model suggests that services be developed which provide a validating environment, the opportunity to enhance skills and a mechanism to accept input from families. PMID- 8453537 TI - The integration of the self-psychological and cognitive-behavioural models in the treatment of borderline personality disorder. AB - The major focus of the non pharmacological treatment of borderline personality disorders is rapidly shifting from long term, psychodynamically oriented therapies to highly structured and explicitly operationalized cognitive behavioural treatment models. The goal of these models is changing targeted maladaptive coping behaviour. This paper examines possible limiting factors to Linehan's model of dialectical behaviour therapy, based on the implications of self-definition-seeking behaviour which is commonly observed in these patients. The extent to which borderline patients' self-definition-seeking behaviour is exaggerated and unremitting in a therapeutic context identifies the primacy of these individuals' striving for self-cohesion. If this need is unrecognized and treatment strategies which address it are not incorporated, the success of cognitive-behavioural treatment models can be unnecessarily (and sometimes severely) compromised. A solution to this problem may lie in the integration of therapeutic principles derived from self-psychology. An outline of this theoretical model and its application in brief therapy on increasing self cohesion are presented. PMID- 8453538 TI - Acquired and developmental brain dysfunction in borderline personality disorder. AB - This paper examines the evidence that brain dysfunction causes borderline personality disorder (BPD). The rules of causation set forth by Sir Bradford Hill will be considered, which include the strength of association, consistency of findings, specificity, temporal relationship, biological gradient, biological plausibility, experimental verification and analogous evidence. Brain dysfunction, in this context, is considered to involve both acquired and developmental neurological (or "organic") brain injuries, as well as the evidence provided by neurological and neuropsychological testing, neurobehavioral models of brain functioning and response to treatment. Biochemical and genetic evidence will not be reviewed, but will be considered in proposing models of brain dysfunction in BPD. It is hoped that this review will provide both the stimulus and possible directions for future research and be of relevance to the clinician assessing and treating patients with BPD. PMID- 8453539 TI - A phase I-II study of epirubicin, 5-fluorouracil, and leucovorin in advanced adenocarcinoma of the stomach. AB - BACKGROUND: To determine the maximum tolerated dose of epirubicin for use in combination with 5-fluorouracil (5-FU) and low-dose leucovorin (LV), a Phase I-II trial was conducted in 37 patients with advanced gastric carcinoma. METHODS: The doses of 5-FU (425 mg/m2) and LV (20 mg/m2), both given intravenously on days 1 5, were held constant while the dose of epirubicin was escalated in cohorts of patients (beginning dose, 50 mg/m2 on day 1). Cycles were repeated every 4 weeks. RESULTS: Significant gastrointestinal symptoms and myelosuppression were observed infrequently at the initial dose level. At a dose of 60 mg/m2 of epirubicin on day 1, however, five of eight patients had significant mucosal toxic effects during the first cycle of therapy. In addition, two patients treated at this dose level had Grade 4 granulocytopenia with insufficient recovery to permit a second course by day 28, and one patient each had severe diarrhea and nausea and vomiting. Among 37 patients with assessable disease, there were 3 complete and 11 partial responses (response rate, 38%). CONCLUSIONS: LV modulation of 5-FU can be incorporated safely into combination chemotherapy with epirubicin and provides a relatively active regimen for treatment of disseminated gastric cancer. PMID- 8453540 TI - Osteosarcomas of the skull. Clinical remarks on 19 cases. AB - BACKGROUND: Osteosarcomas are typically long bone tumors and rarely affect the skull, with most articles reporting single cases. As elsewhere in the body, these lesions may be classified as primary or secondary, chiefly post-Paget and post radiation therapy. METHODS: The authors reviewed the osteosarcomas of the skull diagnosed at the Division of Neurosurgery of "La Sapienza" University of Rome. The patients were placed into two groups, according to the treatment received (prechemotherapeutic era and chemotherapeutic era). In the last five patients, a diagnostic-therapeutic protocol was adopted. RESULTS: The most effective investigations are plain radiographs, computed tomography (CT) with bone windows, and magnetic resonance imaging (MRI), with the latter two allowing assessment of the extraosseous extent of the disease. Chemotherapy has changed the prognosis dramatically, achieving cure in some cases (especially in de novo osteosarcomas). Before the age of chemotherapy, the median survival length was 16 months, but since its introduction, five of nine patients in this study are alive 2 years after diagnosis. The onset of metastases, chiefly to the lung, does not necessarily imply a poor prognosis. The authors propose a schedule for the diagnosis and treatment of new cases of osteosarcoma of the skull. CONCLUSIONS: Plain radiographs, CT targeted on the bone, and MRI are the most important diagnostic tools. Aggressive chemotherapy together with surgery (eventually including local radiation therapy in nontotal macroscopic surgical removal of the lesions) can drastically modify the prognosis of de novo and post-radiation therapy osteosarcomas. PMID- 8453541 TI - Splenic metastasis in hairy cell leukemia. AB - BACKGROUND: Splenic metastasis is uncommon and usually occurs in the setting of widespread visceral metastasis. Splenic metastasis as an initial manifestation of disease and sole site of metastasis has not been reported previously. METHODS: The authors describe a patient with hairy cell leukemia (HCL) with the unexpected finding of metastatic adenocarcinoma in the spleen. Direct inspection at the time of laparotomy and subsequent radiographic studies did not show a primary or additional metastatic tumor. Eventually, he manifested evidence of pulmonary and hepatic metastases and died with fungal sepsis. RESULTS: The splenectomy specimen showed HCL and metastatic adenocarcinoma. Immunohistochemical studies showed adenocarcinoma with diffuse cytoplasmic staining for prostate-specific antigen and focally positive results with prostatic acid phosphatase antigen. Postmortem examination 9 months later showed HCL and widespread metastatic adenocarcinoma. No primary tumor was identified, and multiple tissue blocks of the prostate had negative findings for tumor. CONCLUSIONS: The immunohistologic features of the metastatic adenocarcinoma were interpreted as prostatic in origin. The pattern of isolated metastatic disease in the absence of primary tumor appears to represent another possible atypical disease presentation of prostatic cancer. Hairy cell induced structural and immunologic alterations within the splenic microenvironment may have contributed to this unique clinical presentation. PMID- 8453542 TI - The presence of particles resembling human T-cell leukemia virus type I at ultrastructural examination of lymphomatous cells in a case of T-cell leukemia/lymphoma. AB - BACKGROUND: Cases of adult T-cell leukemia/lymphoma (ATLL) resulting from human T cell leukemia virus type I (HTLV-I) have been observed mainly in the southern part of Japan. Recently, the authors performed a second examination of cutaneous, muscle, and nerve biopsy specimens from a French white woman who died of ATLL in 1979. METHODS: A 67-year-old white woman had a lymphoma diagnosed on a lymph node biopsy. She then had acute pains and a thickened skin on both legs. Blood examination showed a leukocyte count of 16,000/ml with 75% leukemia T-cells. Biopsies were performed on the antero-external surface of the right leg. She died after 2 years of illness. RESULTS: Lymphomatous infiltrates of T-cell origin were seen in the dermis, between muscle fibers, and in a peripheral nerve. The recent ultrastructural examination of a few vacuoles located in the cytoplasm of certain lymphomatous cells showed rounded structures mixed with larger virus-like formations having a central nucleoid and spike material around the envelope. Polymerase chain reaction experiments performed on deparaffinized sections demonstrated the presence of a tax sequence homologous to that of HTLV-I. Other structural genes were not detected. CONCLUSIONS: These results contrast with other ultrastructural studies in which HTLV-I was detected only after cultivation of leukemia cells from patients with ATLL. This case probably resulted from an HTLV-I variant. PMID- 8453543 TI - Soft tissue vascular tumors. A flow cytometric DNA analysis. AB - BACKGROUND: The clinical behavior of soft tissue vascular tumors is difficult to predict on histologic grounds alone. METHODS: To assess the usefulness of DNA flow cytometry in predicting the biologic behavior of these tumors, the authors studied 51 soft tissue vascular tumors by DNA flow cytometry of paraffin-embedded tissue. RESULTS: All 20 capillary hemangiomas, one epithelioid hemangioma, two spindle cell hemangioendotheliomas, and two benign hemangiopericytomas had a diploid DNA content. Of the 20 patients with angiosarcomas, their ages ranged from 9-80 years (mean, 44.0 years), and the mean follow-up period was 16.5 months. Ten tumors (including two postmastectomy angiosarcomas) were cutaneous, six were deep soft tissues, and four were from other sites. These tumors were classified histologically into three types: sinusoidal (n = 10), capillary (n = 7), and mixed type (n = 3). Thirteen of the angiosarcomas (65%) were diploid, and seven (35%) were aneuploid. Three patients with angiosarcoma had lung metastases at initial diagnosis, and seven had them later in the course. Nine patients died of their disease within a period of 18 months after the initial diagnosis. All five patients with malignant hemangiopericytoma died of their disease. Three of these lesions had a diploid DNA content, and two had an aneuploid content. Although it was found that all benign and intermediate-grade malignant tumors were diploid, there were no significant correlations among histologic type, DNA ploidy, and clinical outcome in angiosarcomas and malignant hemangiopericytomas. CONCLUSIONS: Based on this study, DNA analysis has limited value in predicting the biologic behavior of malignant vascular tumors of the soft tissue. PMID- 8453544 TI - Successful treatment of a desmoid tumor with doxorubicin. AB - BACKGROUND: Desmoid tumors are the source of significant morbidity and mortality in patients with Gardner syndrome. METHODS: The authors present a case report and review of the literature. RESULTS: A young woman with an extensive abdominal desmoid had a prolonged response to doxorubicin after she did not respond to more conventional treatments. CONCLUSIONS: To the authors' knowledge, this is the first report of the successful treatment of desmoids with doxorubicin used as a single agent. Reports of the efficacy of chemotherapy in these and related tumors are reviewed. PMID- 8453545 TI - A phase II study of weekly cisplatin followed by cisplatin and ifosfamide in advanced or recurrent cervical carcinoma. AB - BACKGROUND: Ifosfamide is an active agent in cisplatin-resistant cervical cancer. To determine the response rate of the combination of cisplatin and ifosfamide, a Phase II study was conducted of the administration of the combination after weekly cisplatin induction therapy. METHODS: Forty-seven patients with advanced or recurrent cervical carcinoma were treated with 1 mg/kg of cisplatin weekly for six courses, followed by 20 mg/m2 of cisplatin and 1.2 g/m2 of ifosfamide daily for 3 days every 28 days. RESULTS: Objective responses were seen in 11 of 40 (27.5%) assessable patients (complete response, 20%; partial response, 7.5%). The duration of response ranged from 3 months to 26+ months (median, 9+ months). All of the patients who responded to the cisplatin-ifosfamide combination initially responded to weekly cisplatin induction therapy. None of the four patients who had previously received chemotherapy responded. Grade 3 or 4 hematologic toxic effects occurred in 17 of 43 patients (39%). Neurologic and urologic toxic effects were infrequent. The current response rates are not better than the prior experience of the authors with other cisplatin combinations. CONCLUSIONS: These results do not confirm the favorable reports of other authors with cisplatin ifosfamide regimens in cervical carcinoma. The results of ongoing Phase III studies comparing cisplatin-ifosfamide with cisplatin alone in cervical carcinoma are awaited. PMID- 8453546 TI - Intraperitoneal radioactive phosphorus therapy in ovarian carcinoma. Analysis of 313 patients treated primarily or at second-look laparotomy. AB - BACKGROUND: Intraperitoneal radioactive phosphorus (phosphorus-32) has been used in ovarian cancer during the last three decades. In the current study, the survival results, the patterns of recurrence, morbidity rates, and phosphorus-32 distribution scintigrams were reviewed in 313 patients treated with phosphorus-32 colloid. METHODS: Between July 1982 and July 1988, 245 patients with epithelial ovarian carcinoma were treated with phosphorus-32 as primary adjuvant treatment; 59 patients received phosphorus-32 as consolidating therapy after negative results during second-look surgery and 9, after positive findings during second look laparotomy. Fifty patients with negative second-look findings were assigned randomly to receive phosphorus-32 or no treatment. The phosphorus-32 distribution was studied by scintigraphic imaging in 297 patients. RESULTS: The actuarial 5 year crude survival rate was 81% in the group treated with phosphorus-32 adjuvantly and 79% in the group treated after second-look surgery. Crude and disease-free survival rates were similar in both groups randomized at second-look surgery to receive either phosphorus-32 or no treatment. Phosphorus-32 scintigraphy showed major isotopic accumulations in 48 (16%) patients. There were two deaths (0.6%), which, at least partly, could be attributed to the phosphorus 32 treatment. Small bowel obstruction without tumor recurrence occurred in 22 (7%) patients (13 treated surgically and 9 medically) and was not related to any patient characteristic, including phosphorus-32 distribution. CONCLUSIONS: Phosphorus-32 therapy was associated with a considerable number of bowel complications. The occurrence of small bowel obstruction could not be predicted by any patient characteristic. Without an untreated observation group, the authors were unsure whether adjuvant phosphorus-32 treatment conferred a survival advantage. PMID- 8453547 TI - Ovarian carcinoma heterogeneity as demonstrated by DNA ploidy. AB - BACKGROUND: In ovarian carcinoma, DNA ploidy measured by flow cytometric (FCM) analysis is an independent prognostic factor. However, limited sampling may underestimate the extent of ploidy variation (i.e., heterogeneity). Uncovering these hidden populations may explain poor outcomes in patients with ostensibly favorable ploidy patterns. The authors examined ploidy in a mean of 6.4 tumor samples per patient to better assess the occurrence of heterogeneity. METHODS: FCM analysis was performed on multiple samples from 19 cases of advanced, serous ovarian carcinoma. Tumors were considered as heterogeneous by two definitions: (1) the presence of more than one ploidy pattern (e.g., diploidy and tetraploidy); and (2) the existence of DNA indices of sufficient variation so as to characterize two distinct populations of neoplastic cells. RESULTS: With the first definition, 47% (9 of 19) of the tumors were heterogeneous, 37% (7 of 19) homogeneous-aneuploid, and 16% (3 of 19) homogeneous-diploid. These three groups showed no significant differences in histologic type, grade, patient age, stage, or survival. With the second definition, 27% (4 of 15) of the non-diploid cases were heterogeneous and 73% (11 of 15) were homogeneous. When these two groups were compared as to type, grade, patient age, and stage, no significant differences were demonstrated. However, the median survival of the patients with heterogeneous tumors was significantly longer (P < 0.05) than the survival of patients with homogeneous tumors. CONCLUSIONS: Ovarian carcinoma heterogeneity is high when multiple sites are assayed. This suggests conservative interpretation of ploidy when only a single sample is analyzed and examination of multiple samples when practicable. PMID- 8453548 TI - Radioimmunoguided radical prostatectomy and lymphadenectomy. AB - BACKGROUND: The feasibility of using radioimmunoguided surgery (RIGS) (Neoprobe Corp., Columbus, OH) for intraoperative detection of prostate cancer was examined in a pre-Phase I clinical study involving 10 patients having radical prostatectomy and lymphadenectomy. METHODS: Patients were injected with iodine 125-radiolabeled B72.3 monoclonal antibody, which has been shown previously to bind to TAG-72, a pancarcinoma and oncofetal antigen. At a mean of 26 days after injection, RIGS was performed with a specially designed intraoperative gamma detecting probe. RESULTS: By comparing probe counts with counts of appropriate background tissues, the RIGS system successfully localized tumor to the prostate of all 10 patients. Clinically occult and histologically confirmed bilateral intraprostatic tumor was identified in three patients. One additional patient had bilateral positive intraprostatic probe count ratios with the RIGS technique; on histologic examination, tumor was identified unilaterally, and extensive high grade prostatic intraepithelial neoplasia was found on the contralateral side. Probe count ratios were positive in the lymph nodes of three patients; two had tumor confirmed histologically. CONCLUSIONS: The current investigation supports the feasibility of the RIGS technique and the need for additional studies. PMID- 8453549 TI - Clear cell sarcoma of kidney. Two cases in adults. AB - BACKGROUND: Clear cell sarcoma of kidney (CCSK) is an aggressive renal tumor occurring most frequently in the second and third years of life. Although it has been reported in the literature in patients as old as 21 years of age, there has been no report focusing on adults with CCSK. The authors describe two cases of CCSK in men and the findings at autopsy. METHODS AND RESULTS: Histologically, the renal tumors consisted of a homogeneous proliferation of polygonal or short spindle cells with faintly eosinophilic cytoplasm supported by a network of small vessels. Ultrastructurally, clusters of tumor cells were surrounded by collagen bundles. Elongated cytoplasmic processes, dilated rough endoplasmic reticulum, and intermediate filaments in the cytoplasm; primitive desmosome-like junctional structures; and incomplete basal lamina were observed. Immunohistochemically, tumor cells had positive results only for vimentin. Cytokeratins, epithelial membrane antigen, desmin, myoglobin, S-100 protein, neuron-specific enolase, and chromogranin A were not detected in the tumor cells. Both patients died within 2 years of onset of disease, and autopsy showed widespread metastases, especially in the soft tissue and bone. CONCLUSIONS: Morphologic findings and an aggressive clinical course with metastasis to the bone and soft tissue are supportive of the diagnosis of CCSK in these patients. PMID- 8453550 TI - Biologic distinctions between cure and time to death in 2892 patients with intraocular melanoma. AB - BACKGROUND: For certain types of cancer, resection alone rarely achieves a cure, but patients nevertheless tend to have a prolonged survival before they die of the tumor. For other types of cancer, the opposite scenario prevails, suggesting that those biologic mechanisms that allow a curative resection are not identical to those that determine survival time among uncured patients. METHODS: The multivariate log-normal model can be used to detect the association of cured fraction and median survival time of patients with specific prognostic covariates. This model was applied to survival data from 2892 patients with intraocular melanoma who were treated by enucleation. RESULTS: This analysis showed that large tumor size and pleomorphic nucleoli within the tumor were associated independently with a low probability of cure and short median survival time. Advanced patient age and mixed cell type, however, were highly associated with only a short median survival time. CONCLUSIONS: For patients with intraocular melanoma treated only by enucleation, the median survival time is not modulated by the same biologic factors that determine the likelihood of a curative resection. PMID- 8453552 TI - Reduction of the number of neck treatments in patients with head and neck cancer. AB - With modern diagnostic imaging techniques, the head and neck oncologist is faced with increasing information on the status of neck nodes of patients with head and neck cancer. It is often difficult to include this new diagnostic information in clinical management because strategies of neck treatment date from times when only clinical examination was available. Computed tomography, magnetic resonance imaging, and ultrasonography (US) may provide information on the status of neck nodes. In the University Hospital Leiden and the University Hospital Rotterdam, US of the neck, when combined with ultrasonographic fine-needle aspiration biopsy (US-UGF-NAB), has proved to be an accurate diagnostic test for nodal disease. The combined procedure is characterized by high sensitivity and specificity. Therefore, this technique is suited for detecting, demonstrating, and excluding nodal metastases. This article will discuss how to interpret the new diagnostic information supplied by US-UGFNAB. A different approach in the clinical management of the neck, based on techniques from the field of clinical decision analysis, will be presented. It is concluded that US-UGFNAB is a promising concept of methodic use of both cytologic examination and an imaging technique in the examination of patients with squamous cell carcinoma of the upper aerodigestive tract. Application of the test may produce an accurate classification of patients with a head and neck tumor and change indications for elective and therapeutic neck treatment. PMID- 8453551 TI - 1;19 translocation in human meningioma. AB - BACKGROUND: Loss of chromosome 22 represents the most common chromosome abnormality (70%) in meningiomas. The remainder (30%) have a normal karyotype. Not only are the structural changes rare, they also occur simultaneously with various chromosome losses. METHODS: The authors identified and studied the meningiomas of two patients with standard tumor cell culture technique and chromosome preparation. RESULTS: Twenty karyotypes from each meningioma had a 46 modal chromosome number with t(1;19) (q21;p13) in all cells. CONCLUSIONS: The sole change of the (1;19) translocation in meningioma, without any other changes such as chromosome loss, as shown in this study, is unique and has never been reported before in the literature, to the knowledge of the authors. Additional study is needed to learn more about the rate of occurrence and the significant impact on meningeal tumor genesis. PMID- 8453553 TI - Oxygenation of head and neck tumors. AB - BACKGROUND: Tumor hypoxia could play a role in the response to radiation therapy. Few data are available on oxygen tension (pO2) measurements in head and neck tumors. METHODS: The KIMOC-6650 Histograph (Eppendorf, Hamburg, Germany) was used to measure the oxygenation status of normal tissues and head and neck tumors in 20 patients. RESULTS: The median pO2 for normal tissues was 43 mmHg with very low pO2 values (2.0 mmHg or less) recorded in two patients. Low median pO2 levels (10 mmHg or less) were recorded in 2 of 5 primary tumors and in 11 of 15 metastatic lymphadenopathies, with very low values in 11 nodes. The median pO2 in tumors was lower than that of normal tissues in 12 of 15 patients with comparative measurements. Oxygen tension was recorded in three nodes after an evaluation of tissue density (by computed tomographic scanner); in two nodes, the mean and median pO2 values were lower in the hypodense areas than in isodense areas. The data for N2 and N3 nodes showed significantly more values below 2.0 mmHg as nodal size increased (P < 10(-4), by chi-square test). No systematic decrease in pO2 was recorded from the periphery to the center of the tumors. CONCLUSIONS: Very low pO2 values, corresponding to radiobiologic hypoxia, were found in most of these tumors. The prognostic value of these pO2 measurements in regard to treatment response remains to be demonstrated. PMID- 8453554 TI - Intensive recombinant interleukin-2 and alpha-interferon therapy in patients with advanced head and neck squamous carcinoma. AB - BACKGROUND: Cellular immune deficiency is a consistent finding in patients with advanced head and neck cancer. Interleukin-2 and alpha-interferon are modulators of the immune system. METHODS: Eleven patients with recurrent head and neck cancer were treated in a Phase II study of recombinant human interleukin-2 (rIL 2) and alpha-2a-interferon (Roferon-A, Hoffmann-La Roche, Inc., Nutley, NJ). Each course consisted of rIL-2, 3 x 10(6) U/m2/day, as a continuous intravenous infusion over 24 hours for 4 days, and recombinant alpha-2a-interferon, 5 x 10(6) U/m2/day intramuscularly or subcutaneously daily for 4 days. This treatment was repeated weekly for 4 weeks, and then a second cycle was given after a 2-week break. RESULTS: Two patients (18%) achieved a partial response. Toxic effects were substantial. Three of 11 patients experienced Grade 3 hypotension, 3 patients had Grade 3 oliguria, and Grade 3 fatigue was one of the most common reasons for withdrawal from the study. There were no deaths or need for intensive care monitoring. CONCLUSIONS: In view of the 18% response rate, additional investigation of biologic therapy in advanced head and neck cancer is warranted. PMID- 8453555 TI - Acquired immune deficiency syndrome-related pulmonary non-Hodgkin lymphoma regressing after zidovudine therapy. AB - BACKGROUND: Zidovudine is a thymidine analogue that has been reported to have antiviral and antineoplastic activity in vitro. METHODS: The case of a patient with acquired immune deficiency syndrome (AIDS) and a pulmonary non-Hodgkin lymphoma treated with zidovudine and no other treatment is presented. RESULTS: The patient achieved a prolonged partial remission of a pulmonary non-Hodgkin lymphoma while receiving zidovudine alone. CONCLUSIONS: Zidovudine may have antitumor effects in AIDS-related lymphomas and should be evaluated for its antitumor potential. PMID- 8453556 TI - Cyclosporine treatment of refractory T-cell lymphomas. AB - BACKGROUND: Cyclosporine (cyclosporin A, CSA) prolongs the survival of transplanted organs by reducing the transcription of cytokines, especially interleukin-2, that are thought to mediate T-cell expansion and subsequent graft rejection. Recently, CSA has been suggested as a potentially effective agent in the treatment of T-cell neoplasms. As a result, a Phase II trial of CSA was done in patients with refractory T-cell lymphomas. METHODS: Patients with peripheral T cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL) who had disease progression after at least one previous therapy were eligible for participation. CSA was administered orally at a dose of 7.5 mg/kg twice daily, and the patients were followed for disease response and toxicity. RESULTS: A total of 16 patients were treated. Five patients had PTCL, and 11 had CTCL. Most patients were pretreated extensively with chemotherapy and/or radiation therapy. No responses occurred in patients with PTCL. Two of 11 patients with CTCL responded to therapy. Both patients who responded to CSA had recurrent disease that approached baseline levels within 1 week of discontinuing therapy. A second response occurred in both patients after reinstitution of therapy. Although most patients were removed from the study because of disease progression, renal toxicity was significant. CONCLUSIONS: Most patients with refractory T-cell lymphomas did not respond to CSA, suggesting that these malignancies are not interleukin-2 dependent or, alternatively, that CSA did not reach its intracellular target. In the two responding patients, the pattern of repeated rapid regression of disease after CSA administration and subsequent rapid recurrence after a temporary halt in therapy suggested that CSA was cytostatic rather than cytocidal or that the clinical remissions were mediated by the antiinflammatory effects of the drug. PMID- 8453557 TI - Adjuvant cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy after radiation therapy in stage I low-grade and intermediate-grade non-Hodgkin lymphoma. Results of a prospective randomized study. AB - BACKGROUND: In a prospective randomized manner, this study evaluated the effect of adjuvant chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone; CHOP) in patients with Stage I non-Hodgkin lymphoma (NHL) who have achieved a complete response (CR) after radiation therapy (RT). METHODS: Forty four patients with clinical or pathologic Stage I intermediate-grade or low-grade NHL were randomized to receive regional RT alone (median dose, 40 Gy) or regional RT followed by six cycles of CHOP chemotherapy. There were no differences in clinical and pathologic characteristics between the two treatment groups. RESULTS: The median follow-up was 7 years (range, 2-10 years). The actuarial relapse-free survival (RFS) rate for the RT plus CHOP group at 7 years was 83% compared with 47% (P < 0.03) for the RT-alone group. The overall survival (OS) for the two groups was 88% and 66%, respectively (P = 0.2). In patients with intermediate-grade NHL, the 7-year actuarial RFS for RT and CHOP was 86% compared with 20% for RT alone (P = 0.004). The corresponding actuarial survival rates were 92% and 47%, respectively (P = 0.08). In patients with low-grade histologic findings, the addition of adjuvant CHOP did not improve RFS (P = 0.6) or OS. All relapses in this study were at sites remote from the initially involved areas, and in 5 of 11 patients (45%), there were recurrences 5 years or longer after initial treatment. CONCLUSIONS: This study showed that adjuvant CHOP chemotherapy significantly improves RFS in patients with Stage I intermediate-grade NHL who achieve a CR after regional-field RT. The chemotherapeutic regimen favorably affected their probability of survival. PMID- 8453558 TI - Inpatient continuous-infusion interleukin-2 in 788 patients with cancer. The National Biotherapy Study Group experience. AB - BACKGROUND: Interleukin-2 (IL-2), used alone or in combination with adoptive cellular therapy, is one of the most promising biologic therapeutic agents for cancer treatment. METHODS: The National Biotherapy Study Group conducted 15 trials of continuous-infusion IL-2 involving 788 patients with cancer, 638 of whom were evaluable for tumor response. The protocols included administration of IL-2 and lymphokine-activated killer (LAK) cells, IL-2 and cyclophosphamide, IL-2 and tumor-infiltrating lymphocytes, IL-2 and alpha-interferon (IFN), IL-2 and tumor necrosis factor, and IL-2 and LAK alternating with combination chemotherapy. RESULTS: Responses were detected in 33 of 188 patients (18%) with melanomas, 13 of 167 (8%) with renal cell carcinomas, and 1 of 76 (1%) with colorectal cancers. The median survival times in patients with melanoma and renal cell cancer were 9.6 and 9.3 months, respectively. The proportion of patients surviving 1 year were 35% and 43%, respectively. There were responses in 8 of 51 patients (16%) with lung cancer, but many of these patients received IL-2 and LAK alternating with platinum-based chemotherapy. Four of 23 patients (17%) responded who had breast cancer and received IL-2 and IFN. The protocols involving IL-2 plus adoptive cellular therapy produced a higher response rate than those not involving activated cells (48 of 312 [15%] versus 24 of 326 [7%], P = 0.003); however, there was no difference in survival. There was a 1.8% mortality rate attributed to the complications of IL-2 itself. CONCLUSIONS: IL-2 produces durable tumor responses in some patients, especially in those with melanoma and renal cell carcinoma. Because the drug's toxicity is significant and the overall response rates are low, patient selection may be the most important factor in the clinical use of continuous-infusion IL-2 therapy. PMID- 8453559 TI - A phase I study of subcutaneous recombinant interleukin-2 and interferon alfa-2a. AB - BACKGROUND: Both recombinant interferon alfa and interleukin-2 (IL-2) have been shown to have some activity as single agents in metastatic renal cell cancer (RCC), although their activity is minimal in more common solid tumors. Recent preclinical studies have suggested that the combination of these two agents is especially promising. METHODS: Subcutaneous recombinant interferon alfa-2a and IL 2 were administered at one of five dose levels to 33 patients with refractory solid tumors, including 21 patients with RCC. A constant ratio of 5:1 of interferon alfa-2a to IL-2 was used. Interferon alfa-2a and IL-2 were administered three and five times weekly, respectively, for a total of 4 weeks, followed by a rest of 1-3 weeks between cycles. RESULTS: The dose-limiting toxic effects included hypotension, nephrotoxicity, and fatigue. At the recommended Phase II dose of 7.5 million units (MU)/m2 of interferon alfa-2a and 1.5 MU/m2 of IL-2, 12 patients were treated. Ten of 12 completed the 4-week cycle without modification. Four patients at that dose level had Grade 3-4 toxic effects. Partial responses were observed in 4 of 16 assessable patients with RCC. CONCLUSIONS: Subcutaneous interferon alfa-2a and IL-2 can be self-administered safely on an outpatient basis. At tolerable doses, responses can be achieved in metastatic RCC. PMID- 8453560 TI - Sequelae of treatment in 109 patients followed for 5 to 15 years after diagnosis of sarcoma of the bladder and prostate. A report from the Intergroup Rhabdomyosarcoma Study Committee. AB - BACKGROUND: As increasing numbers of young patients with cancer survive, interest in the late effects of therapy is rising. METHODS: The sequelae of treatment were reviewed after a minimum of 5 years of observation in 109 surviving patients with sarcoma of the bladder or prostate who were enrolled in the Intergroup Rhabdomyosarcoma Studies I and II (1972-1984). The 82 male and 27 female patients were 3 weeks to 19 years of age when the diagnosis was made (median, 2 years) and were 5-29 years of age at last contact (median, 11 years). Treatment consisted of chemotherapy with vincristine, dactinomycin, and cyclophosphamide and bladder irradiation in nearly all patients. RESULTS: Fifty-four patients underwent total cystectomy, and 10 had a partial cystectomy. Of the 55 patients with bladder preservation, 1 had a urinary conduit with a nonfunctioning bladder. Thus, 54 bladders (50% of the total) remained in place as part of the urinary tract. There was no information regarding bladder function in two patients. Satisfactory bladder function was found in 38 patients (73%), 9 were incontinent, and 5 had urinary frequency with or without nocturia. Posttherapy hematuria was detected in 29% of patients. Nine of the 31 patients (29%) with follow-up renal imaging studies had a structural abnormality, chiefly hydronephrosis, which was more frequent in those with urinary diversion. Positive urine cultures were found mainly among those with enteric urinary conduits, but only two cases of pyelonephritis were documented. Abnormalities of irradiated bone and bowel were observed infrequently. Only one patient had a significantly elevated blood urea nitrogen or serum creatinine value, and only one patient was hypertensive. Most patients were still prepubertal at last follow-up. Of 24 patients who were intrapubertal or postpubertal, 7 (29%) were receiving sex hormone replacement because of delayed pubertal development. Height was decreased by 25% or more in 11 patients, as confirmed by growth chart analysis. Secondary surgical procedures other than repeat biopsy or cystectomy consisted primarily of urinary conduit revisions and repair of bowel adhesions or fistulous tracts. Information about psychosocial status was limited. CONCLUSIONS: Overall, 50% of the patients retained their bladders, and 73% of them had satisfactory bladder function. Renal function was preserved in nearly every patient. PMID- 8453561 TI - Management of locally recurrent breast cancer. AB - BACKGROUND: Locoregional recurrences occur commonly in women with breast cancer and often have grave prognostic implications. Major controversies exist concerning the prophylaxis, implications, and treatment of such relapses and are the focus of this review. METHODS: The relevant medical literature was reviewed and analyzed. RESULTS: Locoregional recurrences may be prevented by postoperative radiation therapy; however, this has little impact on survival. Postoperative systemic therapy prevents locoregional relapse, but less efficiently than radiation therapy. When these modalities are combined, radiation therapy often is delayed until after several cycles of chemotherapy. Optimal sequencing remains controversial. Most patients with locoregional relapses have an exceedingly poor outlook. Radiation therapy provides excellent local control; however, the addition of combination chemotherapy should be considered for patients with defined poor prognostic features. The clinical impact of recurrence in the breast after breast-conserving primary treatment now is emerging. Such local relapses do not have the dreaded prognostic implications of locoregional relapse after mastectomy, but are a marker for an increased risk of dissemination. Standard therapy in this setting remains mastectomy. Additional breast-conserving surgery may be considered in the context of clinical trials for patients with certain favorable features. Conversely, some local relapses after breast-conserving surgery have a poorer prognosis, and the addition of adjuvant systemic therapy should be considered in addition to mastectomy. CONCLUSIONS: The heterogenous nature of locoregional relapses has made it difficult to conduct prospective randomized clinical trials. However, many retrospective data exist, making it possible to recommend rational treatment approaches for these patients. PMID- 8453562 TI - American Cancer Society Workshop on Adolescents and Young Adults with Cancer. Workgroup #1: Long-term care and lifetime follow-up. PMID- 8453563 TI - American Cancer Society Workshop on Adolescents and Young Adults with Cancer. Workgroup #2: Insurance and employability. PMID- 8453564 TI - American Cancer Society Workshop on Adolescents and Young Adults with Cancer. Workgroup #3: Psychosocial and emotional issues and specialized support groups and compliance issues. PMID- 8453565 TI - American Cancer Society Workshop on Adolescents and Young Adults with Cancer. Workgroup #4: Clinical research implications. PMID- 8453566 TI - Multiple prognostic factors and outcome analysis in patients with cancer. Communication from the American Joint Committee on Cancer. AB - The authors report the establishment of a new Committee of the American Joint Committee on Cancer that has two objectives as follows: (1) to review the methods available to estimate outcome and (2) to study certain tumors to determine whether an expanded list of prognostic factors can be formulated into new prognostic systems that will have scientific value and clinical utility for treatment selection and staging. PMID- 8453567 TI - Dogma and inquisition in medicine. Breast cancer as a case study. AB - This case study demonstrates the similarity between the development of dogma and the persecution of deviants during the Spanish Inquisition and that in medicine using breast cancer as an example. Regarding breast cancer, the dogma of therapy became separate from the underlying hypothesis and, like the religious dogma enforced by the Inquisition, it required inflexible adherence. Apostates were publicly chastened. This serves to inhibit debate and the exploration of alternative hypotheses, both of which are essential for the advancement of scientific knowledge. Adherance to dogma is antithetical to the conditional and approximate nature of truth in science. PMID- 8453568 TI - Adenoma accompanied by superficial squamous cell carcinoma of the esophagus. AB - BACKGROUND: Adenoma of the esophagus is a rare type of esophageal submucosal tumor. METHODS: An immunohistochemical and histopathologic study is reported of specimen from a patient with adenoma of the esophagus. RESULTS: The eighth reported case of esophageal submucosal adenoma without Barrett epithelium is described. The patient was a 58-year-old man with an adenoma and carcinoma of the esophagus. The adenoma showed papillotubular structures lined with two layers of cuboidal cells within the submucosa and lamina muscularis mucosae, and the carcinoma was of the superficial squamous cell type confined to the submucosa. CONCLUSIONS: Morphologic findings suggested that this adenoma had originated from the duct of the esophageal gland proper. PMID- 8453569 TI - Prevention of human pancreatic cancer cell-induced hepatic metastasis in nude mice by dipyridamole and its analog RA-233. AB - BACKGROUND: Several studies have provided evidence suggesting that platelets play a key role in tumor metastasis. A number of antiplatelet agents have been used to prevent tumor metastasis in animal models and humans. Antiplatelet agents, dipyridamole (adenosine transport inhibitor), and RA-233 (inhibitor of cAMP PDE) were used to prevent tumor-cell-platelet interactions both in in vitro and in vivo systems; however, the data were not very conclusive. METHODS: Our studies used dipyridamole and RA-233 alone and in combination to investigate their effects on human pancreatic tumor cells (RWP-2)-induced platelet aggregation in human blood and on hepatic metastasis in nude mice. To examine effects of dipyridamole and RA-233 on liver metastasis, the tumor cells (RWP-2) were injected intrasplenically in nude mice grouped into control, dipyridamole (8 mg/kg), RA-233 (8 mg/kg), and dipyridamole plus RA-233 (8 mg/kg each). The agents were administered intraperitoneally 1 hour before and 24 hours after the tumor cell injection. RESULTS: When dipyridamole and RA-233 were used alone, only weak to moderate effects were seen on RWP-2 tumor cell-induced platelet aggregation. However, these agents, when combined, strongly inhibited the tumor cell-induced aggregation in human platelet-rich plasma. In tumor metastasis experiments, reductions of approximately 70% in hepatic nodules and 90% in surface area occupied by the tumor were seen with the combination treatment (dipyridamole plus RA-233) as compared with the control group of mice. CONCLUSIONS: This study suggests that the combination of dipyridamole and RA-233 provides an effective intervention for the antithrombotic approach to the treatment of cancer metastases. PMID- 8453570 TI - Prognostic factors in laryngeal carcinoma. Experience in 296 male patients. AB - BACKGROUND: Laryngeal cancer is the primary cause of death among patients with head and neck cancer in Argentina. Different prognostic factors have been incidentally dealt with in a number of articles, but there are few studies of prognostic variables, such as age, tobacco, and alcohol, using multifactorial analysis. METHODS: Between 1969-1987, 296 male patients with epidermoid carcinoma of the larynx treated at the Institute of Oncology "Angel H. Roffo" were studied regarding prognostic factors of survival. The effect of age, tobacco, alcohol, histologic grade, extent of primary tumor, and cord mobility on survival were assessed by means of the Cox proportional-hazards model. RESULTS: The univariate analysis showed that primary tumor extent, nodal involvement, stage, alcohol intake, previous tracheostomy, and cord mobility were statistically significant predictors of survival. Multivariate analysis disclosed only nodal involvement, alcohol intake, and cord mobility as statistically significant variables in regard to survivorship. With these variables, a hazard index was calculated for each patient, and four risk groups were formed. Five-year survival rates were as follows: Group A, 79%; B, 69%; C, 47%; and D, 14% (A versus C, P < 0.005; A versus D, P < 0.005). CONCLUSIONS: This study confirmed the prognostic impact of nodal involvement and also showed the importance of cord fixation and alcohol drinking as predictors of survival. PMID- 8453571 TI - Experimental study of the therapeutic effects of folate, vitamin A, and vitamin B12 on squamous metaplasia of the bronchial epithelium. AB - BACKGROUND: Vitamin deficiency may be related to carcinogenesis. Cytologic examinations of sputum have already found that the administration of folate and vitamin B12 suppressed the development of squamous metaplasia and atypia in smokers' airways. The authors investigated the effect of folic acid, vitamin B12, and vitamin A on the formation of metaplasia and hyperplasia in methylcholanthrene (MCA)-treated rats. METHODS: The SD strain of rats received 10 mg of MCA intratracheally and was divided into six groups as follows: (1) vitamin A; (2) folic acid; (3) vitamin B12; (4) vitamin B12 with folic acid; (5) a combination of vitamin A, folic acid, and vitamin B12; and (6) no vitamins. The Lower respiratory tract epithelia of the rats were examined histologically 20, 32, and 36 weeks after MCA administration and at the end of the experiment. RESULTS: A clear difference was detected between the group receiving folic acid and that receiving vitamin A. In the former group, metaplasia was found in only one rat, atypia was not found, and hyperplasia with marked changes was present in less than 50% of other groups. In the latter group, atypia was found in all of the metaplastic foci. CONCLUSIONS: It was suggested that the epithelial hyperplasia and metaplasia of respiratory tract induced by MCA can be suppressed by the administration of folic acid. PMID- 8453572 TI - Intra-arterial cisplatin with or without radiation in limb-sparing for canine osteosarcoma. AB - METHODS: Forty-nine dogs with spontaneously occurring osteosarcoma underwent limb sparing surgery after preoperative therapy consisting of intra-arterial cisplatin alone or intra-arterial cisplatin in combination with doses of radiation from 20 40 Gy in 10 fractions. All resections were marginal, and the defect was repaired with a cortical allograft. RESULTS: Local tumor control was strongly influenced by the percent necrosis in the excised specimen. Overall, the estimated 1-year local recurrence rate was approximately 32% (by life-table estimate). Dogs with less than 75% necrosis had an estimated 1-year recurrence rate of 65%; those with greater than 75% necrosis had an estimated 1-year recurrence rate of 15% (P = 0.004, by log-rank test). Local recurrence was influenced by the radiation dose. Dogs receiving 28 Gy or less had an estimated 50% 1-year recurrence rate, and those receiving 32 Gy or more had an estimated 8% 1-year recurrence rate (P = 0.03, by log-rank test). Normal host bone more frequently became necrotic at doses of 36 Gy or more. CONCLUSIONS: Intra-arterial cisplatin in combination with moderate doses of radiation (32 Gy) can achieve a high percent tumor necrosis while maintaining host bone viability. Survival was limited by distant metastasis but was lengthened by treatment compared with some earlier findings. PMID- 8453573 TI - Pilomatrix carcinoma. AB - BACKGROUND: Pilomatrix carcinoma, a malignant variant of pilomatrixoma, is extremely rare. The authors report 20 patients with pilomatrix carcinoma and review the pertinent literature. METHODS: Tumors showing histologic features of pilomatrix carcinoma were selected from the files of the Armed Forces Institute of Pathology. Clinical data of the 20 selected patients were reviewed, and follow up information was obtained. Sections stained with hematoxylin and eosin were studied in all patients. Special stains were used in selected patients. RESULTS: Pilomatrix carcinomas were asymptomatic dermal and subcutaneous masses with a predilection for the posterior neck and back. Tumors varied in size, from 1-10 cm (mean, 4.6 cm), and occurred more often in middle-age men, with a male:female ratio of 4:1 (mean age, 45 years). Histologically, pilomatrix carcinomas are characterized by sheets and islands of proliferating atypical basaloid cells with an infiltrating border. Transition to squamous cells, clear cells, areas of necrosis and mitoses often are seen. Keratinization with formation of keratin cysts, shadow cells, and trichohyalin and keratohyalin granules are found in all tumors, in conjunction with calcification and foreign body giant cell reaction, just as are seen in benign pilomatrixoma. Follow-up of 17 patients revealed local recurrence in 10 (59%), with multiple recurrences in 3. One patient had pulmonary metastasis, and one died of extensive local spread of the tumor. CONCLUSION: Pilomatrix carcinomas are locally aggressive tumors that have a tendency to recur, especially when they are incompletely excised. Greater anaplasia and deep soft tissue infiltration were associated with a higher incidence of recurrence and death. Wide excision is the preferred treatment. The role of radiation therapy is unclear. PMID- 8453574 TI - Pathologic findings from the National Surgical Adjuvant Breast Project protocol B 06. 10-year pathologic and clinical prognostic discriminants. AB - BACKGROUND: Prognostic pathologic and clinical features for 10-year survival were determined from 22 pathologic and 5 clinical variables encountered in 1090 node negative and 651 node-positive patients enrolled in NSABP protocol B-06. METHODS: All factors were first screened univariately. Those exhibiting P values < 0.01 were entered into multivariate Cox regression models. The model with the best fit consisted of 951 negative-node and 496 node-positive patients. RESULTS: Better survival in node-negative patients was noted for whites rather than blacks, for patients with favorable tumor types (tubular, mucinous, papillary) rather than intermediate (lobular invasive, classical medullary, and not otherwise specified [NOS] combinations) or unfavorable forms (NOS pure and atypical medullary), and for tumors with good rather than poor nuclear grade. Number of nodal metastases, degree of tumor elastosis, and patient age younger than 40 years of age and 65 years of age and older in addition to nuclear grade and race were found significant for node-positive patients. Relative risks for combinations of these prognostic factors were multiplicative. CONCLUSIONS: The prognostic factors for node-negative patients were similar to those observed for this cohort at 8 years. Some differences noted between patients of both nodal groups in NSABP B-04 and B 06 may be related to selection requirements in the latter and hence different patient characteristics or more speculatively a change in tumor biology. PMID- 8453575 TI - Combined analysis of ploidy and cell kinetics on fine-needle aspirates from breast tumors. AB - BACKGROUND: DNA ploidy and cell kinetics determined by flow-cytometric (FCM) analysis have provided relevant information on the natural history of breast cancer. These highly feasible and evaluable assays are particularly appropriate for small samples from fine-needle aspirates (FNA) to complement cytologic information for diagnosis of breast lesions. METHODS: DNA content and the percentage of cells in the cell cycle phases were evaluated on FCM DNA histograms from 281 consecutive FNA of benign and malignant breast lesions. RESULTS: FCM analysis was possible in 93% of FNA. Qualitative concordance in DNA content between FNA and surgical specimens was observed in 82% of the patients. Of the 145 aneuploid FNA, 144 (99%) were histologically diagnosed as carcinomas. The presence of only diploid clones was observed in 115 FNA: rapidly proliferating (S+G2M > 12%) diploid lesions proved to be histologically malignant in 67% of patients, and slowly proliferating diploid lesions were histologically benign in 79% of patients. False-positive results of ploidy and cell kinetics were observed in 1 and 10 patients, respectively. Of the 163 cancers evaluable for cytology and FCM, 158 were positive at cytology. The presence of aneuploid or of diploid rapidly proliferating clones in cytologically false-negative aspirates resulted in the detection of four additional cancers. CONCLUSIONS: Flow cytometric analysis of ploidy and cell kinetics on FNA could be a valuable tool complementary to cytology for breast cancer diagnosis. PMID- 8453576 TI - The increasing prevalence of benign proliferative breast lesions in Japanese women. AB - BACKGROUND: Although the increasing incidence of breast cancer in Japan has been well-documented, the possibility that there also has been an increase in the frequency of benign proliferative breast disease in Japanese women has not been previously studied. METHODS: The authors compared the histologic findings in a series of 266 consecutive benign breast biopsy specimens from 1974 to 1975 (Group I) to those in a series of 266 similar biopsy specimens accessioned at the same institution in Japan one decade later (i.e., 1984 to 1985; Group II). The extent of sampling was similar in both groups. The specimens were categorized as showing nonproliferative lesions, proliferative lesions without atypia, or atypical hyperplasia using the criteria of Dupont and Page. RESULTS: Proliferative lesions without atypia were significantly more common in biopsy specimens from Group II than those from Group I (16.2% versus 9%; P = 0.01). Although atypical hyperplasias were twice as common in Group II as in Group I, these lesions were uncommon in both groups (2% in Group II versus 1% in Group I, p = NS). The differences in pathologic findings between the two groups were most evident in younger women. For patients younger than 40 years of age, the prevalence of proliferative lesions (with or without atypia) was 18% for Group II and 6% for Group I (P = 0.003). For patients 40 years of age or older, proliferative lesions were seen in 17% of patients in Group II and 13% in Group I (P value, not significant). CONCLUSIONS: The frequency of benign proliferative breast lesions in Japanese women, particularly among women younger than 40 years of age, is increasing. These observations are consistent with the results of previous studies in North America that have demonstrated a relationship between benign proliferative breast lesions and the development of breast cancer. PMID- 8453577 TI - Evidence of tumor heterogeneity in cervical cancers and lymph node metastases as determined by flow cytometry. AB - BACKGROUND: The incidence and significance of tumor heterogeneity in primary tumors and metastatic lymph nodes were investigated in Stage IB-IIA cervical cancers. METHODS: Paraffin-embedded tissues from 96 radical hysterectomy specimens were dewaxed, disaggregated, and subjected to dual parameter flow cytometry. Three-dimensional histograms were generated to delineate different tumor populations. A DNA index difference of at least +/- 0.15 was used to define tumor heterogeneity. RESULTS: Mean DNA index difference of various tumor populations was 0.29 +/- 0.13. Among 69 patients with normal lymph nodes, there were 12 patients (incidence, 17.4%) with tumor heterogeneity in the primary tumors. Of 27 patients with metastatic lymph nodes, 5 (incidence, 18.5%) had evidence of tumor heterogeneity in the primary tumor, and 18 of 47 (incidence, 38.3%) had tumor heterogeneity in metastatic lymph nodes. When using DNA index to determine clonal origin of metastatic lymph nodes, as many as 60% of the metastases could not be traced to the primary tumor. Tumor heterogeneity was associated with a 40% reduction in median survival time. However, because of the small number of patients with tumor heterogeneity, statistical analyses did not show prognostic significance. CONCLUSIONS: Tumor heterogeneity appeared to be a common characteristic of early cervical carcinoma. Additional study is needed to fully evaluate its prognostic value. PMID- 8453578 TI - CA 125 and CA 19-9 immunolocalization in normal, hyperplastic, and carcinomatous endometrium. AB - BACKGROUND: Elevated levels of tumor-associated antigens, such as CA 125, have been reported in patients with endometrial carcinomas. This study was done to evaluate the frequency and tissue distribution of CA 125 and CA 19-9 in normal and neoplastic endometrium. METHODS: Consecutive tissue sections were immunohistochemically evaluated using primary antibodies directed against CA 125 and CA 19-9. Antibody-antigen binding was demonstrated using the avidin-biotin technique. RESULTS: CA 125 expression was related to the phase of the menstrual cycle and was most prominent during secretory phase. Positive staining (5% or more of the glandular epithelium) for CA 19-9 was noted in only 4 of 20 patients with normal endometrium. Positive staining for CA 125 (5% or more of the epithelium) was present in 68% of the carcinomas; another 8% of the tumors contained focal staining for CA 125. Positive staining for CA 19-9 was demonstrated in 60% of tumors; another 8% of the tumors showed focal staining for CA 19-9. The markers were concordant in 76% of the tumors evaluated. CONCLUSIONS: Although CA 125 was uniformly expressed by the glandular cells in normal endometrium, CA 19-9 expression appeared to be related to the prevalence of the Lewis A phenotype. Endometrial carcinomas also frequently express these antigens, and the degree of expression was related to the grade and cell type of the tumor. PMID- 8453579 TI - Perioperative coagulopathy in patients undergoing primary cytoreduction. AB - BACKGROUND: This study was performed to determine the frequency of a perioperative coagulopathy in patients undergoing primary cytoreduction for ovarian cancer or carcinoma of the peritoneum and to identify variables that might predict this phenomenon. METHODS: A retrospective review of 90 patients undergoing primary cytoreduction for ovarian cancer or carcinoma of the peritoneum was performed at Cedars Sinai Medical Center. Univariate analysis was performed to test the relationship between 15 variables and coagulopathy status. RESULTS: Six patients (6.7%) developed a perioperative coagulopathy that was unrelated to preoperative subcutaneous heparin or dilution. Coagulation disturbances developed intraoperatively before packed erythrocyte replacement equivalent to one blood volume. Four patients (4.4%) required a repeat laparotomy due to continued postoperative bleeding unresponsive to blood component replacement. Vascular pedicles were not the cause of bleeding in any patient. Univariate analysis demonstrated a significant association between perioperative coagulopathy and the following variables: ascites volume (P = 0.009), estimated blood loss (P = 0.002), preoperative serum albumin less than 3.5 g/dl (P < 0.0001), and metastasis greater than 10 cm (P = 0.033). CONCLUSIONS: Patients undergoing primary cytoreduction who have ascites, preoperative serum albumin less than 3.5 g/dl, or metastases greater than 10 cm may be at increased risk for development of a perioperative coagulopathy. PMID- 8453580 TI - Dysgerminoma of the ovary. An immunohistochemical study of tumor-infiltrating lymphoreticular cells and tumor cells. AB - BACKGROUND: Human neoplasms often are accompanied by an inflammatory infiltrate. It has been proposed that this represents an immunologic response to the tumor. Dysgerminoma, a germ cell tumor of the ovary, is a classic example of this phenomenon. The authors investigated the immunophenotype of the tumor infiltrating lymphoreticular cells (TIL) and tumor cells in this rare malignancy. METHODS: Tissue from seven dysgerminomas of the ovary was fixed in formaldehyde solution and embedded in paraffin and investigated immunohistochemically with a broad panel of monoclonal antibodies. In one case, additional immunohistochemical investigations were performed on cryopreserved tumor tissue. RESULTS: All seven tumors showed a marked cellular stromal reaction with formation of disseminated granulomas similar to that seen in the closely related testicular seminoma. The TIL were preponderantly T-cells (CD43+, CD45RO+, OPD4+) and macrophages/epithelioid cells (MAC387+, CD68+), B-cells (CD20+, Ki-B3+), natural killer cells (CD57+), and immune-accessory cells (CD1+, CD35+) were rare in most cases. In the one case in which cryopreserved tissue was available, most of the intratumoral T-cells belonged to the CD8+ (cytotoxic/suppressor) subtype, and most of the intratumoral T-cells expressed the alpha/beta heterodimer of the T cell antigen receptor; gamma/delta + T-cells were exceedingly rare. Some of the macrophages/epithelioid cells were found to express activation antigens (interleukin-2 receptor, transferrin receptor, HLA-DR2). Antibodies against placental alkaline phosphatase and pancytokeratin each stained tumor cells in six cases. Virtually no tumor cells were found to express major histocompatibility complex (MHC) Class II antigens. CONCLUSIONS: The immunohistochemical findings concerning the tumor cells and TIL in dysgerminoma of the ovary provide additional evidence of a close relation to seminoma of the testis. PMID- 8453581 TI - Stage at presentation and survival of white and black patients with prostate carcinoma. AB - BACKGROUND: Black men are known to have a higher incidence and mortality from prostate carcinoma than white men and are more likely to have a more advanced stage or grade of disease diagnosed. METHODS: In a Veterans Administration Medical Center where black and white men have the same eligibility for medical care, the authors reviewed the stage at presentation of 861 consecutive cases of prostate carcinoma diagnosed from 1969-1990. In addition, survival, stratified by race, stage, and grade, was determined on all men in whom prostate cancer was diagnosed from 1969-1985 (525 patients). RESULTS: It was found that 26% of white and 52% of black men with prostate carcinoma presented with Stage D disease. Similar proportions of white and black men with prostate carcinoma presented with Stage D disease between 1969-73 as between 1986-90. The overall survival was poorer for black men because of their higher proportion of Stage D disease, but stratified for grade and stage, survival was similar in both races. CONCLUSIONS: This study suggests that factors other than eligibility for medical care may be responsible for the higher proportion of black men with prostate carcinoma presenting with Stage D prostate carcinoma. PMID- 8453582 TI - Meta-analysis of radiation therapy with and without adjuvant chemotherapy for malignant gliomas in adults. AB - BACKGROUND: The value of chemotherapy after standard postoperative external beam radiation in the treatment of malignant gliomas remains controversial. Despite recent recommendations from the Brain Tumor Cooperative Group that chemotherapy should be considered part of the standard treatment of patients with high-grade astrocytomas, several recent trials have questioned the efficacy of this approach. METHODS: Using results from 16 randomized clinical trials involving more than 3000 patients, the authors compared the survival rates of patients who received radiation alone or radiation with chemotherapy. The combined data were analyzed using the statistical method of meta-analysis as described by DerSimonian and Laird. RESULTS: The estimated increase in survival for patients treated with combination radiation and chemotherapy was 10.1% at 1 year (95% confidence interval, 6.8, 13.3%) and 8.6% at 2 years (5.2, 12.0%). These absolute increases in survival (treated-control [TC]) in patients treated with chemotherapy represent relative increases (T-C)/C of 23.4% at 1 year (15.8, 30.9%) and 52.4% at 2 years (31.7, 73.2%). This survival advantage is conferred by several different chemotherapeutic agents. When the prognostic variables of age and histology are factored into the analysis, however, the data suggest that the survival benefit from chemotherapy occurs earlier in patients with anaplastic astrocytoma (AA) than in patients with glioblastoma. CONCLUSIONS: The authors concluded that chemotherapy is advantageous for patients with malignant gliomas and should be considered part of the standard therapeutic regimen. Additional randomized trials using optimal radiation and chemotherapy may still be needed to precisely define which subgroups of patients, based on prognostic variables, will benefit most from chemotherapy after radiation. PMID- 8453583 TI - Predictive value of fine-needle aspiration of the thyroid in the classification of follicular lesions. AB - BACKGROUND: Fine-needle aspiration has been less valuable in the diagnosis of follicular lesions than for other neoplasms of the thyroid. It has been observed that follicular carcinoma is found in microfollicular, but not macrofollicular lesions, and this has served as a guide to management for many surgeons. The authors attempted to determine what cytologic parameters might usefully distinguish these types of follicular lesion. METHODS: The histologic findings and cytology of 56 thyroid lobectomies for follicular lesions that had adequate preoperative fine-needle aspiration of the thyroid (FNAT) were reviewed. Histologic specimens were classified into macrofollicular, mixed, and microfollicular groups. Cytologic features examined included the presence of colloid, irregularity of cell arrangements within groups, the presence and size of flat and folded cell sheets, three-dimensional clusters, and microfollicles and macrofollicles. RESULTS: Of the histologic specimens, 15 were preponderantly (> 70%) microfollicular, 19 were mixed, and 22 were predominantly (> 70%) macrofollicular. Three cytologic features were useful in their distinction: none of the predominantly microfollicular but 24% of the mixed and predominantly macrofollicular had abundant colloid (P = 0.048). Likewise, none of the predominantly microfollicular but 27% of the mixed and predominantly macrofollicular had large follicles (P = 0.026). Finally, 73% of the predominantly microfollicular but only 37% of the mixed and predominantly macrofollicular showed irregularity or crowding of cells in groups (P = 0.018). CONCLUSIONS: Used in combination, abundant colloid, regular spacing, and large follicles are helpful in distinguishing macrofollicular and mixed lesions from microfollicular ones, which have a higher malignant potential. PMID- 8453584 TI - Noncutaneous T-cell lymphomas. Recognition of a lymphoma type (large cell anaplastic) with a relatively favorable prognosis. AB - BACKGROUND: The clinical relevance of the updated Kiel classification for T-cell lymphomas is discussed. Large series with long-term follow-up are needed to investigate the clinical relevance of a separation into high- and low-grade T cell lymphomas, based on the Kiel classification. METHODS: The clinicopathologic data of 97 consecutive noncutaneous T-cell lymphomas, diagnosed in the Comprehensive Cancer Center Amsterdam, between July 1, 1985, and December 1, 1990, were reviewed and analyzed for their prognostic significance. RESULTS: Immunohistochemistry contributed substantially in the diagnosis of T-cell lymphoma. Using the updated Kiel classification, many difficulties occurred in classifying these lymphomas. Only large cell anaplastic lymphoma (LCAL) and lymphoblastic lymphoma (LBL) were classified with a high degree of confidence. Variables associated with prolonged survival were classified as LCAL and low stage of disease (Stage I and II) at clinical presentation. Multivariate survival analysis revealed that subtype (grouped as LCAL versus non-LCAL) was selected as the most significant variable, closely followed by stage of disease at clinical presentation (grouped as Stage I/II versus Stage III/IV). LCAL was associated with a significantly better survival than were all other types of high-grade T cell lymphoma (P = 0.018) and tended to be associated with a better survival than low-grade T-cell lymphoma (P = 0.067). No significant differences in survival were found between the other types of T-cell lymphoma or between high- and low grade T-cell lymphomas as classified according to the updated Kiel classification. Other variables, such as sex and age (younger than 60 years versus older than 60 years) had no significant influence on survival time. CONCLUSIONS: This study indicates that the clinical relevance of classifying primary noncutaneous T-cell lymphomas according to the updated Kiel classification is limited because only a diagnosis of LCAL has prognostic relevance in predicting survival. PMID- 8453586 TI - Acute superior vena cava syndrome after central venous catheter placement. AB - Most cases of superior vena cava (SVC) syndrome are secondary to malignant disease and subacute in their presentation. Acute cases of SVC syndrome have been described, with the majority of these being precipitated by thrombosis after central venous catheterization. The authors report a case of acute SVC syndrome after central venous catheter placement, which was not due to thrombosis, but rather caused by a catheter occluding a previously subclinical stenosis of the SVC. Resolution of the clinical SVC syndrome occurred after catheter withdrawal. PMID- 8453585 TI - Prognostic factors for patients with Hodgkin disease in first relapse. AB - BACKGROUND: This study aims to identify factors that predict outcome after salvage therapy for patients with Hodgkin disease (HD) in first relapse. METHODS: Between 1969 and 1985, 627 patients with Pathologic Stage IA-IIIB HD were treated at the Joint Center for Radiation Therapy. With a median follow-up time for survivors of 135 months, 138 patients (22%) have experienced relapse. One hundred twenty-seven of these were retreated with curative intent and form the basis of this report. RESULTS: The complete response (CR) rate after retreatment was 79%. The 10-year actuarial freedom from second relapse (FSR) was 53%, and the 10-year survival rate from the time of first relapse was 57%. For patients experiencing relapse after initial radiation therapy (RT) alone (n = 110), the 10-year FSR and overall survival rates were 58% and 62%, respectively. Histologic type was the single most important prognostic factor for second CR rate, FSR, and survival. Patients with nodular sclerosis or lymphocyte predominant (NS/LP) histologic type had a 91% second CR rate, 67% 10-year FSR rate, and 75% 10-year survival rate, compared with 66%, 44%, and 43%, respectively, for patients with mixed cellularity or lymphocyte depleted (MC/LD) histologic type. For patients who experienced relapse after initial combined modality therapy (CMT; n = 17), the 10 year FSR and overall survival rates were 13% and 24%, respectively. CONCLUSION: This study demonstrates that patients who experience relapse after RT alone can be effectively salvaged with combination chemotherapy. The implications of these results for clinical decision making are discussed. PMID- 8453587 TI - Malignant lymphoma imitating hepatitis. AB - BACKGROUND: Involvement of the liver is common in low-grade lymphomas and usually occurs as disseminated disease. Less common causes include primary liver lymphoma, usually of B-cell origin, and hepatosplenic lymphoma, a recently described T-cell lymphoma. METHODS: The medical records of three patients with clinical features of hepatitis who were found at autopsy to have lymphoma involving primarily the liver and spleen were reviewed. Tissue sections were stained with hematoxylin and eosin after fixation. Immunohistochemistry evaluation was performed by the immunoperoxidase technique on tissue fixed in formaldehyde solution and embedded in paraffin. Frozen tissue was available for additional immunophenotypic studies in one patient (Patient 1). RESULTS: Presenting signs included fever, jaundice, hepatomegaly, and elevated liver enzyme levels, especially serum alkaline phosphatase and bilirubin. Palpable lymphadenopathy was absent. Clinical evaluation indicated hepatitis. Lymphoma was the unexpected finding at postmortem examination after a rapidly deteriorating clinical course. The entire liver in each patient showed a predominant portal lymphomatous infiltration. Two patients had small cleaved cell lymphomas, and one had a large cell lymphoma. Immunologically, one of the small cleaved cell lymphomas was of B-cell phenotype and one was of T-cell origin. The large cell lymphoma showed immunologic staining only with the CD15 antibody (LeuM1). CONCLUSIONS: Lymphoma diffusely involving the liver frequently is associated with splenic involvement and may present as primary hepatic dysfunction. In contrast to previous reports of hepatosplenic T-cell lymphoma, this series suggests that lymphoma involving primarily the liver and spleen can be diverse in cytologic and immunologic characteristics. PMID- 8453588 TI - Primary extracranial rhabdoid tumors. Clinicopathologic features and response to ifosfamide. AB - BACKGROUND: Malignant rhabdoid tumor (MRT) is an aggressive, invariably lethal tumor that is resistant to multimodal therapy. METHODS: The authors reviewed the clinicopathologic features, treatment, and outcome of 13 children (7 boys and 6 girls) with diagnoses of primary extracranial MRT at St. Jude Children's Research Hospital between 1981 and 1990. RESULTS: The median age at diagnosis was 8 months (range, 10 weeks-18 years). Primary sites included the kidney (seven patients), liver (three patients), soft tissue of scapula, posterior mediastinum, and retroperitoneum. Seven patients had metastatic disease (lungs, six patients; cutaneous hemangioma, one patient). Ten patients had surgical resection of primary tumor (complete, nine patients; incomplete, one patient). Eleven patients had chemotherapy with multiple agents. Three of four chemotherapy responses observed were with regimens containing ifosfamide. Partial responses (PR, > 50% reduction in tumor size) were obtained in one patient who received single-agent ifosfamide during disease relapse (PR lasting 2 months), one patient who received a combination of ifosfamide, carboplatin, and etoposide at diagnosis (PR lasting 5 months), and one patient who was treated with bleomycin, cyclophosphamide, doxorubicin, and vincristine at diagnosis (PR lasting 5 months) and subsequently with ifosfamide in combination with carboplatin and etoposide during disease relapse (PR lasting 4 months). All patients died at a median period of 5 months (range, 0.5-30 months) after diagnosis. CONCLUSIONS: Based on this review, the authors recommend using ifosfamide alone or in combination with carboplatin and etoposide in front-line therapy for malignant rhabdoid tumor. PMID- 8453589 TI - Primary hepatic neuroendocrine carcinoma in a child. Morphologic, immunocytochemical, and molecular biologic studies. AB - BACKGROUND: Primary neuroendocrine tumor of the liver is uncommon, and virtually all reported patients with the tumor have been adults. Most of the tumors were carcinoids. The authors report an 8-year-old girl with primary hepatic neuroendocrine carcinoma. METHODS: Histologic, ultrastructural, and immunocytochemical studies and Southern blot analysis of tumor N-myc DNA were performed in the patient. RESULTS: Histologically, the tumor revealed a characteristic organoid pattern with a spectrum of differentiation varying from well-differentiated carcinoid-like areas to poorly differentiated pleomorphic areas. Ultrastructural features included neurosecretory granules and interdigitating cytoplasmic extensions. The tumor cells showed immunoreactivity to neuron-specific enolase (NSE), S-100 protein, chromogranin, and synaptophysin. No evidence of amplification of tumor N-myc DNA was present. However, the molecular weight of the tumor N-myc DNA (1.8 kb) was significantly lower than the normal control (from normal liver tissue) (2.0 kb). CONCLUSIONS: This report documents the occurrence of primary hepatic neuroendocrine carcinoma in a child. Thorough studies and complete clinical evaluation are essential to the establishment of diagnosis. The result of N-myc DNA analysis probably is attributable to deletion of part of the tumor N-myc gene. The clinical implication of this finding is unknown, and additional investigation is warranted. PMID- 8453590 TI - Early cystic/necrotic changes after hyperfractionated radiation therapy in children with brain stem gliomas. Data from the Childrens Cancer Group. AB - BACKGROUND: A higher total dose of radiation therapy administered in fractionated lower individual doses twice daily (hyperfractionated radiation therapy) has been reported to improve survival for children with brain stem gliomas. However, this higher dose of radiation therapy may cause more sequelae. METHOD: Eighty-eight children with brain stem gliomas were treated with 100 cGy twice daily to a total dose of 7200 cGy. Patients were carefully followed up for treatment-related clinical or radiographic worsening. RESULTS: Thirteen (15%) had intralesional cystic/necrotic changes within 8 weeks of completion of treatment. Children with these changes had a variable clinical course, including steady deterioration in one child; initial improvement, followed by progressive deterioration in three; and initial improvement, followed by deterioration, with subsequent improvement or prolonged stabilization of condition without additional antineoplastic treatment in nine. CONCLUSION: This latter "triphasic" course suggests that "early" worsening after hyperfractionated radiation therapy at 7200 cGy may be a sequelae of therapy, rather than a symptom of progressive tumor growth. This has substantial implications for patient care and evaluation of the efficacy of treatment. PMID- 8453591 TI - The World Health Organization histological classification of tumours of the upper respiratory tract and ear. A commentary on the second edition. AB - The second edition of Histological Typing of Tumours of the Upper Respiratory Tract and Ear, in the World Health Organization series International Histological Classification of Tumours, provides a comprehensive classification of tumors and tumor-like lesions occurring in (1) the nasal cavity and paranasal sinuses; (2) the nasopharynx; (3) the larynx, hypopharynx, and trachea; (4) the external ear; and (5) the middle and inner ear. The classification includes several newly recognized entities and many that were omitted from the first edition on account of their rarity. The terminology and definitions of several tumor types have been revised in the light of experience gained during the past 12 years. This article discusses the revised classification with special reference to some of the major changes in the listings, terminology, and definitions. PMID- 8453592 TI - Detection of variant Ph-positive chronic myelogenous leukemia involving chromosomes 1, 9, and 22 by fluorescence in situ hybridization. PMID- 8453593 TI - Loss of the Y-chromosome in a malignant Sertoli tumor. PMID- 8453594 TI - Double t(1;7)(p36;p11) in a megakaryocytic crisis of chronic myelogenous leukemia with variant t(5;9;22). AB - A 56-year-old man with chronic myelogenous leukemia (CML) who presented with a variant Ph chromosome, t(5;9;22)(q13;q34;q11), developed a unique additional chromosomal change of a double reciprocal t(1;7)(p36;p11) during the accelerated phase. A minor clone that had two copies of 1p+ and a copy of 7p- with a normal chromosome 7 was observed simultaneously. The patient underwent a megakaryocytic crisis. Surface marker of the blasts was positive for CD13, CD33, HLA-DR, CD41a, and CD42b, and negative for CD14 and lymphoid markers. Sequential chromosome analysis suggests that the double t(1;7) was caused by a multistep event consisting of duplication of both derivative chromosomes accompanied by loss of normal chromosomes 1 and 7. This may be the first report of a double reciprocal chromosomal translocation in a hematopoietic neoplasm. PMID- 8453595 TI - DNA amplification in human gastric carcinomas. AB - We recently identified a genomic domain at chromosome 10q26 that is highly amplified in the gastric carcinoma cell lines KATO III and SNU-16 and contains the BEK/K-sam gene, which encodes several growth factor receptors. A contiguous segment of 200 kb spanning this gene was amplified in five of 139 (3.6%) primary gastric carcinomas, all of them classified as poorly differentiated tumors. There was no amplification of this genomic region in a variety of other solid tumors. The overall frequency of gene amplification among the gastric carcinomas rose to 19.4% when MYC, ERBB2, and INT2 were included in the analysis, with significant association with advanced tumor stage. Amplification of various genomic regions in solid tumors may be more frequent than previously estimated. PMID- 8453596 TI - Trisomy 4 in acute myeloblastic and acute lymphoblastic leukemia. AB - We report three cases of trisomy 4 in acute leukemia. This alteration was detected as the sole cytogenetic abnormality in a case of FAB M4 leukemia; it occurred in association with 5q deletion in a case of M1, and concomitant with Ph chromosome and trisomy 17 in a case of L2 leukemia. The latter case represents the fourth report of trisomy 4 in acute lymphoblastic leukemia. PMID- 8453597 TI - Unique clinical features and prognostic significance of the translocation (6;11) in acute leukemia. AB - A translocation (6;11)(q26-27;q23) was detected in four male patients diagnosed with acute T-cell lymphoblastic leukemia and acute myelomonocytic and monocytic leukemias. This acquired reciprocal translocation appears to be associated with acute leukemias in young men who present clinically with localized infection, and a moderate leukocytosis. There was a poor response to antileukemic chemotherapy and a short overall survival. Aggressive treatment strategies should be considered in the treatment of these high-risk leukemias. PMID- 8453598 TI - Folate-sensitive and aphidicolin-inducible fragile sites are expressed in the genome of the domestic cat. AB - Peripheral blood lymphocytes from three clinically normal domestic cats were cultured for folate-sensitive and aphidicolin-inducible fragile site expression. Induction of folate-sensitive fragile sites was accomplished by culturing cells with trimethoprim plus caffeine. Chromosomes from all cats expressed both folate sensitive and aphidicolin-inducible breaks and gaps. There were no significant differences between the two methods of fragile site induction in the percentage of cells expressing chromosome breaks and gaps or the mean number of breaks and gaps per cell. All three cats expressed specific chromosome breaks resembling fragile sites at A1q21-22, A1p22, and B1q32. All three sites were induced by aphidicolin. The sites at A1q21-22 and B1q32 were also induced in folate deficient medium. This is the first report of the induction of chromosomal fragile sites in a feline species. PMID- 8453599 TI - Chromosome abnormalities in patients treated with 4-hydroperoxycyclophosphamide purged autologous bone marrow transplantation. AB - Autologous bone marrow transplantation (ABMT) offers potentially curative therapy for patients with acute leukemia and lymphoma, yet little information exists about the chromosome abnormalities observed in ABMT recipients. Clonal abnormalities of chromosome 1 were reported by van den Akker. We report the cytogenetic results of 55 patients who underwent ABMT between November 1987 and July 1990: acute nonlymphocytic leukemia (ANLL, 22), acute lymphocytic leukemia (ALL, eight), Hodgkin's disease (seven), lymphoma (16), other (two). ANLL patients received busulfan and cytoxan, and the others received cytoxan and total body irradiation as their preparative regimen before transplant. BM was purged ex vivo with 4-hydroperoxycyclophosphamide (4-HC) at 30-100 micrograms/ml before reinfusion to kill tumor cells. Cytogenetic analysis was performed before and after transplant. Between one and four posttransplant specimens of BM were analyzed per patient (range 36-921 days). Chromosome abnormalities were observed in 14 of 55 patients after transplant. Seven had clonal abnormalities; all were in leukemic relapse, and one karyotype had complex rearrangements. Clonal abnormalities of chromosome 1 were not observed. Seven patients had nonclonal changes, and three of these have had overt clinical relapse. Our data suggest that clonal abnormalities observed posttransplant are best explained by clinical relapse of tumor and that ex vivo marrow purging with 4-HC is not likely to induce clonal chromosome abnormalities in normal cells. Long-term observation of these patients will be required to answer that question definitively, however. PMID- 8453600 TI - A recurrent chondromyxoid fibroma with chromosome aberrations ins(5;2)(q13;p21p25) and 2p deletion: a case report. AB - We report a patient with a recurrent chondromyxoid fibroma, a rare benign tumor of the bone with clonal aberrations in chromosomes 2 and 5. Karyotyping, chromosome painting, interphase cytogenetics by in situ hybridization, and DNA flow cytometry were used. The karyotype was interpreted as 46,XX,der(2)ins(5;2)(q13;p21p25),der(2)ins(5;2)(q13;p21p25), der(5)ins(5;2) (q13;p21p25). PMID- 8453601 TI - Consistent numerical chromosome aberrations in congenital fibrosarcoma. AB - Cytogenetic analysis of a congenital fibrosarcoma of the volar forearm from a 2.5 month-old boy revealed a mosaic karyotype 46,XY/49,XY,+11,+17,+20. This pattern of specific trisomies provides additional support to the cytogenetic findings in five cases of congenital fibrosarcoma reported previously. Trisomy 11 appears to be characteristic of congenital fibrosarcoma with additional trisomies 8, 17, and 20 as common findings. PMID- 8453602 TI - Complex karyotypic abnormalities including t(8;22) in a patient with chronic lymphocytic leukemia. AB - The case of a 49-year-old Chinese man with B-cell chronic lymphocytic leukemia (B CLL) is presented. Complex karyotypic abnormalities comprising t(8;22)(q24;q11), trisomy 7, a deletion of 11q, and two small marker chromosomes were observed in PWM-stimulated cultures of his peripheral blood cells. To our knowledge, this is the first report of a t(8;22) in CLL. PMID- 8453603 TI - Chromosomal analysis of two neuroblastomas. AB - We report the results of cytogenetic analysis in two children with neuroblastoma. The analysis was performed on slides obtained from a 24-hour bone marrow (BM) culture or by a direct method of the primary tumor tissue. The structural and numeric karyotype aberrations were established, including structural aberrations of chromosome 1. The finding of i(1q) and t(1;5)(p22;q13) is of interest because these chromosome aberrations are rare in this type of disease. PMID- 8453604 TI - A new chromosomal anomaly associated with mature B-cell chronic lymphoproliferative disorders: del(7)(q32). AB - Among 63 patients with chronic lymphoproliferative disorders (CLPD) studied cytogenetically in our laboratory, four showed a del(7)(q32); in two it was the sole cytogenetic anomaly and in two it was part of a complex karyotype. We suggest that despite the rarity of this anomaly, it could be related to CLPD. PMID- 8453605 TI - Central neurocytoma: a cytogenetic case study. PMID- 8453606 TI - A new case of isolated tetrasomy of chromosome 8 in a patient with therapy related myelodysplastic syndrome: confirmation by chromosome painting in metaphase and interphase nuclei. PMID- 8453607 TI - Translocation (14;18) in a patient with common acute lymphoblastic leukemia (FAB l2) PMID- 8453608 TI - Detection of tumor-specific homozygous deletions in human biopsies by polymerase chain reaction. AB - Cancer is associated with homozygous deletions of specific DNA sequences that are in some instances too small to be detectable by cytogenetic methods or Southern blot analysis. Such small tumor-specific deletions can be detected, however, by the polymerase chain reaction (PCR) provided that tumor cells are meticulously and verifiably isolated from contaminating nontumor cells. Nontumor cells can give positive PCR results and thus obscure the detection of deletions. Using a method that allows accurate and verifiable excision of tumor cells for subsequent PCR analysis, homozygous deletions, one in a putative tumor suppressor gene on chromosome 8 and one in the p53 gene, were detected in two out of 20 human lung carcinomas investigated. PMID- 8453609 TI - Detection of minimal residual disease by polymerase chain reaction in patients with different hematologic diseases treated by bone marrow transplantation. AB - Thirteen male patients affected by different hematologic diseases who underwent bone marrow transplantation (BMT) with female donors were investigated by cytogenetic analysis and polymerase chain reaction (PCR) amplification of a DNA sequence specific for the Y chromosome. In six of these patients, PCR showed the presence of the Y chromosome-related sequence; in only three of these did cytogenetic analysis confirm the presence of mixed chimerism. In the remaining three patients, the results of the PCR were confirmed by in situ hybridization on cell nuclei with a probe for the alpha-satellite of the Y chromosome. We compare results obtained with the two methods and discuss the meaning of the minimal residual disease detected by PCR in patients submitted to BMT. PMID- 8453610 TI - Dual Alu polymerase chain reaction primers and conditions for isolation of human chromosome painting probes from hybrid cells. AB - A method for rapid and efficient production of chromosome- and chromosome-region specific probes for fluorescent in situ hybridization (FISH) detectable by simple fluorescent microscopy is described. The procedure is based on simultaneous use of two inter-Alu-polymerase chain reaction (PCR) primers for extraction of highly heterogeneous human DNA from interspecific somatic cell hybrids containing the chromosome regions of interest. Probes so produced do not hybridize to centromeric sequences and simultaneously band the target chromosomes, making them useful for unambiguous identification of chromosomal elements and breakpoints associated with cancer. PMID- 8453611 TI - Expression of sulfated glycoprotein 2 is associated with carcinogenesis induced by N-nitroso-N-methylurea in rat prostate and seminal vesicle. AB - To understand the molecular mechanism of carcinogenesis in androgen-dependent tumors, we have searched for new markers which are associated with this process. In normal rat prostate and seminal vesicle, sulfated glycoprotein 2 (SGP-2) messenger RNA is barely detectable. However, we have found high levels of SGP-2 expression in the epithelial component of carcinomas of the prostate and seminal vesicle after initiation with N-nitroso-N-methylurea and promotion with testosterone propionate. We have also observed induction of SGP-2 expression in epithelial cells at early stages in carcinogenesis when cytologically malignant cells first begin to appear. SGP-2 has been reported previously to be associated with a variety of models of programmed cell death (apoptosis), including the prostate following castration. Our present findings provide a novel marker for carcinogenesis in the rat prostate and seminal vesicle. PMID- 8453612 TI - Antibody-targeted delivery of doxorubicin entrapped in sterically stabilized liposomes can eradicate lung cancer in mice. AB - Cancer chemotherapy is limited by adverse side effects resulting from toxicities to normal tissues. Targeted delivery of drugs to diseased tissues in vivo would help to reduce these side effects. Liposomes containing lipid derivatives of polyethylene glycol have circulation times sufficiently long to allow for effective in vivo drug delivery. Polyethylene glycol liposomes, containing entrapped doxorubicin, targeted to KLN-205 squamous cell carcinoma of the lung by means of specific antibodies attached at the liposome surface were capable of reducing tumor burden to a high degree and eradicating tumor in a significant percentage of mice. PMID- 8453613 TI - A homozygous deletion within the carbonic anhydrase-like domain of the Ptprg gene in murine L-cells. AB - Protein tyrosine phosphatases, on purely theoretical grounds, were suggested as possible tumor suppressor genes, and receptor protein tyrosine phosphatase gamma (PTPRG) has been proposed, on the basis of its location at human chromosome region 3p14.2, specifically as a tumor suppressor gene for renal cell carcinoma. We have isolated murine genomic and complementary DNA clones for analysis and mapping of the murine Ptprg locus; interspecific backcross analysis showed that the Ptprg locus maps to the centromeric region of mouse chromosome 14. We also observed a homozygous, intragenic deletion in the Ptprg gene in all clonal derivatives of the original L-cell strain, a methylcholanthrene-treated mouse connective tissue cell line which produces sarcomas in syngeneic mice. The deletion begins in the second intron of the carbonic anhydrase-like domain of the Ptprg gene and ends in the fourth intron of the carbonic anhydrase-like domain. At the genomic level, perhaps several hundred kilobases of DNA are deleted; at the complementary DNA level the 400 base pairs comprising exons 2, 3, and 4 of the carbonic anhydrase-like domain are deleted. By reverse transcription polymerase chain reaction, an amplified fragment is produced from L-cell mRNA which is 400 base pairs shorter than the wild type gene product, suggesting that the deleted gene is transcribed and may produce a protein product. Thus, mouse L cells have lost one Ptprg allele and sustained an intragenic deletion in the other; such allele loss and mutation frequently occur at tumor suppressor gene loci. PMID- 8453614 TI - Signaling by integrins: implications for tumorigenesis. PMID- 8453615 TI - Presence of point mutations in the N-ras gene in radiation-transformed rat embryo cells. AB - We study the transforming ability of X-rays in multistep carcinogenesis by irradiating primary rat cells which contain transfected c-myc oncogene. X irradiation induces fully transformed phenotypes, including anchorage-independent growth and tumor formation in nude mice. Of seven foci examined, five exhibited an A to G conversion in codon 61 of the N-ras oncogene. Another transformed isolate has a single G to A base substitution in codon 14 in the same oncogene, while no point mutation is detected in the other focus. This is the first in vitro demonstration of the association between point mutation and X-ray transformed cells. PMID- 8453616 TI - A link between ras and metastatic behavior of tumor cells: ras induces CD44 promoter activity and leads to low-level expression of metastasis-specific variants of CD44 in CREF cells. AB - The activated oncogene c-Ha-ras induces expression of the surface glycoprotein CD44 in cloned rat embryonic fibroblasts (CREF). Induction is transcriptional as shown by transient cotransfections of c-Ha-ras expression constructs and CD44 promoter reporter gene constructs and depends on the presence of an AP-1 binding site at position -110. Increased transcript levels for the standard isoform of CD44 (CD44s) are accompanied by the appearance of alternatively spliced RNAs and the synthesis of variants of CD44 (CD44v). These CD44v molecules differ from the standard type by the addition of sequences in the extracellular portion of the molecules. The occurrence of CD44v molecules in CREF cells upon induction of the CD44 promoter is probably due to leakiness of the splice control in these cells since stable transfection with c-Ha-ras does not alter the CD44v/total CD44 ratio. Upon ras overexpression, however, using an inducible mouse mammary tumor virus-ras construct, a transient increase of CD44v/total CD44 ratio of 3-4 has been determined suggesting that a burst of ras expression, in the genetic background of CREF cells, influences both promoter activity and splice control or accuracy. The expression of CD44v proteins is responsible for the metastatic potential in a variety of tumors (U. Gunthert et al., Cell, 65: 13-24, 1991). Also in CREF cells expression of CD44v correlates with metastatic behavior, ras transfected CREF cells are not only fully transformed but also give rise to metastatic spread as measured in the spontaneous metastasis assay. The adenoviral oncogene E1A counteracts ras-induced promoter function and, consequently, inhibits metastatic behavior without extinguishing transformation. PMID- 8453617 TI - Detection of DNA adducts in human oral tissue: correlation of adduct levels with tobacco smoking and differential enhancement of adducts using the butanol extraction and nuclease P1 versions of 32P postlabeling. AB - Samples of clinically normal oral tissue were obtained from patients undergoing surgery for intraoral squamous cell carcinoma. DNA was extracted from samples obtained from 20 tobacco smokers, four exsmokers, and nine nonsmokers and analyzed for the presence of aromatic DNA adducts using two distinct modifications of the 32P postlabeling assay. 32P postlabeling following butanol extraction enhancement revealed a much wider range and substantially higher levels of DNA adducts than obtained following nuclease P1 enrichment. Adduct levels in smokers, exsmokers, and nonsmokers were 1133 +/- 354, 785 +/- 251, and 660 +/- 317 amol/microgram of DNA (+/- SD), respectively. The elevation of adduct levels in smokers compared with either nonsmokers or non- and exsmokers combined is statistically significant (P < 0.005). These observations are consistent with epidemiological evidence linking tobacco smoking with oral cancer. The differential enhancement of DNA adducts with the two 32P postlabeling protocols indicate that aromatic amines and nitroaromatics may be important sources of the DNA adducts detected in human oral tissue. PMID- 8453618 TI - Glucuronidation of carcinogen metabolites by complementary DNA-expressed uridine 5'-diphosphate glucuronosyltransferases. AB - Five UDP glucuronosyltransferases (UGT) were synthesized from complementary DNAs expressed in COS 7 cells and were tested for their capacities to glucuronidate a range of 2-acetylaminofluorene and benzo(a)pyrene-hydroxylated metabolites. Three forms, UGT1*06, UGT2B1, and UGT2B2 [names of UGT forms follow recommended nomenclature (B. B. Burchell et al., DNA Cell Biol., 10: 487-494, 1991)], had similar capacities to glucuronidate the reactive metabolite, N-hydroxy-2 acetylaminofluorene. The less reactive 1-, 3-, 5-, and 8-hydroxy derivatives of this aromatic amine were glucuronidated by UGT1*06 and UGT2B2 to varying degrees, but these were not substrates of UGT2B1. The three isozymes also glucuronidated phenolic metabolites of benzo(a)pyrene. UGT1*06 was more active toward 2- and 5 hydroxybenzo(a)pyrene, whereas UGT2B1 preferentially glucuronidated the 4- and 11 hydroxy derivatives and UGT2B2 preferentially glucuronidated the 1-, 2-, 8-, and 9-hydroxy metabolites. Two other UDP glucuronosyltransferases, UGT2B3 and UGT2B6, that glucuronidated testosterone when expressed in COS 7 cells were both inactive toward all the carcinogen metabolites tested. These results demonstrate that the glucuronidation of metabolites of 2-acetylaminofluorene and benzo(a)pyrene is mediated by at least three UDP glucuronosyltransferases and that each form glucuronidates a unique spectrum of metabolites. PMID- 8453619 TI - Chronopharmacology of high-dose busulfan in children. AB - In bone marrow transplantation, high-dose busulfan is given p.o., usually every 6 h over 4 consecutive days. Since this repeated administration might alter busulfan disposition, fluctuations in busulfan plasma levels were studied over the 4-day treatment period in 21 children (median age, 5 years) with malignant solid tumors. In addition, urinary excretion of unchanged busulfan was measured every 6 h in 4 patients. Busulfan (37.5 mg/m2 for 16 doses) was given on an empty stomach at 12 p.m., 6 p.m., midnight, and 6 a.m. for 4 consecutive days, starting at 12 p.m. Trough plasma levels, i.e., concentration 6 h after each dose and just before the next one, and urinary excretion of busulfan were measured using a gas chromatography-mass spectrometry assay. Busulfan trough plasma levels exhibited a significant circadian rhythm with a higher mean level at 6 a.m. compared to that at 12 p.m., 6 p.m., and midnight. This rhythm was characterized by a double amplitude (mean +/- SD) of 42 +/- 14% and an acrophase (maximum) occurring at 5:48 a.m. +/- 115 min. In addition, once the steady state was reached, no decreasing trend was observed in any patient. Busulfan renal clearance proved to be low since only 5.4 +/- 1.2% of the given dose were excreted unchanged in urine. In the 4 patients studied, busulfan urinary excretion exhibited a significant circadian rhythm which was apparently linked to the physiological circadian rhythm in urinary output. Ten of 20 evaluable patients developed hepatic venoocclusive disease (HVOD). A significant circadian rhythm in the plasma level was found in both HVOD and non-HVOD patients with no difference between the two groups with regard to the 24-h mean, amplitude, or acrophase. Thus, the circadian changes in busulfan trough plasma levels observed at the steady state were not related to the occurrence of HVOD in these children with solid tumors. Moreover, since this rhythm was stable from day 2 to day 4, it should not compromise dose adjustment. PMID- 8453620 TI - Interleukin-1 alpha and interleukin-6 act additively to inhibit growth of MCF-7 breast cancer cells in vitro. AB - We studied the effects of interleukin-1 alpha (IL-1) and interleukin-6 (IL-6) on MCF-7 breast cancer cells to determine whether these cytokines act additively/synergistically to alter cell growth and metabolism. We found that IL 1 alone (1000 units/ml) inhibited cell growth to a greater degree (83.8%) than IL 6 alone (29.2%, P < 0.001). The combination of IL-1 + IL-6 caused greater inhibition of growth (92.9%, P < 0.02) than either cytokine alone. The additive effect was dose dependent for both IL-1 and IL-6. IL-1 and IL-6 also antagonized estradiol (10(-9) M) stimulated growth. Antagonism by the combination was greater than for either cytokine alone (P < 0.001). IL-1 or IL-6 alone each down regulated the estrogen receptor (36.7%, P < 0.01, and 23.2%, P < 0.05, respectively), but the combination IL-1 + IL-6 did not cause a significantly greater effect than IL-1 alone. Neither IL-1 or IL-6 blocked estradiol stimulation of progesterone receptor (PR) synthesis; however, the combination IL 1 + IL-6 increased PR content by 28.4% (P < 0.01). IL-1, but not IL-6, increased secretion of transforming growth factor-beta (TGF-beta) by 2.45-fold over 72 h (P < 0.01). The increase was time dependent (detectable at 24 h) and dose dependent (maximum increase of 5.3-fold, 10,000 units/ml, P < 0.02). IL-1-induced TGF-beta secretion was blocked by estradiol (10(-9) M). Neither cytokine altered secretion of insulin-like growth factor-1. These findings indicate that IL-1 and IL-6 act additively to inhibit growth in the absence or presence of estradiol and modulate the estrogen receptor and progesterone receptor content of these cells. TGF-beta may mediate the effects of IL-1; however, other pathways appear to be required for the additive effects of these cytokines. PMID- 8453621 TI - Pituitary tumors in mice exposed prenatally to diethylstilbestrol. AB - Hyperprolactinemia and prolactinomas are among the abnormalities reported for women exposed prenatally to diethylstilbestrol (DES). To pursue this issue in an animal model replicating the other abnormalities of prenatal DES exposure, pituitary glands were studied in the offspring of CD-1 mice receiving an i.p. injection of 1 or 2 micrograms DES/g body weight during late pregnancy. Among 132 mice exposed prenatally to DES and then raised to terminal illness, there were 24 pituitary tumors compared to only 1 tumor among 64 controls. The tumors consisted predominantly of cells with an eccentric nucleus and cytoplasm characterized by an acidophilic core and basophilic rim. These cells were identified as lactotrophs on the basis of prolactin immunohistochemistry and by an expected variation in frequency relative to physiological states. Evaluation of ovaries from the same mice revealed a deficiency of corpora lutea and an elevated incidence of ovarian tumors. These findings are consistent with abnormal sex differentiation of the fetal hypothalamus being the cause of most adverse effects from prenatal DES exposure. PMID- 8453622 TI - Pharmacokinetic and pharmacodynamic advantages of pirarubicin over adriamycin after intraarterial hepatic administration in the rabbit VX2 tumor model. AB - Intraarterial chemotherapy with Adriamycin (ADM) has shown limited advantages over i.v. administration, with no reduction in systemic toxicities and modest decrease in peripheral plasma levels. In an effort to improve the selectivity of i.a. anthracycline chemotherapy, we compared pirarubicin (4'-O tetrahydropyranyladriamycin, THP) and ADM in the surgically implanted VX2 rabbit tumor model. Both drugs were administered at the same dose (0.5 mg/kg) either by the intraarterial hepatic route (i.a.h.) or by the i.v. route. Anthracycline plasma and tissue levels were determined by high-performance liquid chromatography with fluorescence detection. ADM peak plasma concentration and area under the curve were not significantly reduced after i.a.h. administration compared to the i.v. route; however, ADM tumor concentration was 1.9-fold higher following i.a.h. administration compared to the i.v. infusion. After THP administration by the i.a.h. route, systemic exposure (area under the curve) was markedly reduced (8-fold) compared to the same dose administered i.v. These findings correlated well with the very low concentration of the drug in heart tissue following i.a.h. infusion. After i.a.h. administration, tumor THP concentrations were 10.5 times higher compared to the i.v. route. The pharmacokinetic advantage of i.a.h. administration of THP also led to a better antitumoral effect, as shown by a significantly lower tumor growth rate [3 +/- 2% (SD)] in the i.a.h.-treated animals compared to the i.v.-treated groups (58 +/- 9%). Administration of ADM by the i.a.h. route was also inferior to i.a.h. THP. Taken together, our results suggest a clear-cut advantage of THP over ADM for i.a.h. locoregional chemotherapy, because of higher local tumor concentrations, greater antitumoral effect, and lower systemic exposure following the i.a.h. administration of THP. This anthracycline analogue could also be of therapeutic advantage in tumors partially resistant to anthracyclines that would become vulnerable to the high local concentrations achieved with i.a.h. administration. Based on these encouraging results, clinical trials using THP administered by the i.a.h. route were initiated. PMID- 8453623 TI - Antitumor activity of the weekly intravenous push schedule of 5-fluoro-2' deoxyuridine +/- N-phosphonacetyl-L-aspartate in mice bearing advanced colon carcinoma 26. AB - We have investigated the effects of N-(phosphonacetyl)-L-aspartate (PALA) administered i.v. as a single dose (100 mg/kg) on the antitumor activity of 5 fluoro-2'-deoxyuridine (FdUrd) and 5-fluorouracil (FUra), on the pharmacokinetic parameters of FdUrd and FUra, and on the tumor pyrimidine ribonucleotide triphosphate pools in mice bearing advanced colon carcinoma 26 and leukemia 1210. The antitumor activity was evaluated with PALA administered i.v. 24 h prior to the maximum tolerated dose of FUra and FdUrd administered by: (a) 4 days of continuous infusion (schedule 1, c.i. days 1-4); (b) daily for 4 days by i.v. push (schedule 2, i.v. days 1-4); and (c) weekly for 3 weeks (schedule 3, i.v. weekly for 3 weeks). The maximum tolerated doses of FdUrd were 20, 150, and 400 mg/kg/day and for FUra were 25, 50, and 80 mg/kg/day for schedule 1, 2, and 3, respectively. At the maximum tolerated doses, the antitumor activity in mice bearing advanced colon carcinoma can be summarized as follows: (a) FdUrd is significantly more active than FUra; (b) for both drugs the weekly for 3 weeks i.v. push schedule is superior to the c.i. or i.v. push daily for 4 days schedules; (c) pretreatment with PALA enhances the antitumor activity of FdUrd and FUra and resulted in 95 and 13% complete responses, respectively; (d) long term survivors with FUra could only be achieved in the presence of PALA; in mice bearing leukemia 1210 cells, FdUrd or FUra with or without PALA exhibited no significant antitumor activity when PALA was administered in a single dose 24 h prior to fluoropyrimidine treatment; and (e) in C-26 and L1210, PALA reduced the pools of CTP and UTP equally, to about 10% of controls with significant difference in their rates of recovery. PMID- 8453624 TI - Protective effects of recombinant human interleukin-1 alpha in doxorubicin treated normal and tumor-bearing mice. AB - Experiments were performed to determine whether treatment with recombinant human IL-1 alpha (rhuIL-1 alpha) would protect C3H mice from the toxic effects of the widely used chemotherapeutic agent, doxorubicin (DXR). Pretreatment of mice with rhuIL-1 alpha was found to protect 85-90% of mice tested from the acute toxic effects of a lethal dose of doxorubicin (25 mg/kg). Late deaths (> 20 days post DXR) were observed in a substantial proportion (40-45%) of rhuIL-1 alpha pretreated mice. However, the data clearly demonstrate a beneficial effect of rhuIL-1 alpha pretreatment on the overall survival of mice challenged with DXR, since both the median survival (32 days) and proportion (53%) of surviving mice were significantly increased (P < 0.0001) compared to the control group (8 days and 14%, respectively). The beneficial effects mediated by rhuIL-1 alpha treatment were both dose- and schedule-dependent and were associated with decreases in the level and duration of DXR-induced neutropenia, and amelioration of the suppressive effects of DXR on myeloid progenitor cells (granulocyte/monocyte colony forming units) as evidenced by milder depressions in marrow cellularity and enhanced recovery of granulocyte/monocyte colony forming unit activity. Finally, pretreatment of mice bearing a solid tumor with rhuIL-1 alpha permitted effective dose escalation with DXR that resulted in decreased tumor growth rates and increased survival (90%) as compared to non-rhuIL-1 alpha treated groups (20% survival). Thus, effective chemotherapeutic dose escalation is made feasible by rhuIL-1 alpha pretreatment of mice, but may ultimately be limited by nonhematological toxicities associated with DXR. PMID- 8453626 TI - Regression of human breast carcinoma tumors in immunodeficient mice treated with 9-nitrocamptothecin: differential response of nontumorigenic and tumorigenic human breast cells in vitro. AB - We have shown recently that the plant alkaloid camptothecin and its derivatives inhibited growth of human carcinoma and melanoma cells in vitro and induced regression of advanced human malignant melanoma tumors growing in immunodeficient (nude) mice. Here, we have extended these studies to show that the camptothecin derivative 9-nitro-20(S)- camptothecin (9NC) induces complete regression of advanced breast carcinoma tumors growing in nude mice. We also report that 9NC inhibits growth of nontumorigenic and tumorigenic breast cells in vitro. However, flow cytometry studies show that 9NC elicits differential effects on the cell cycle of nontumorigenic and tumorigenic cells. In general, 9NC-treated nontumorigenic cells accumulate slowly at the G2 phase of the cell cycle with no cell death. In contrast, 9NC-treated tumorigenic cells transverse rapidly from G1 to S phase followed by cell death. Removal of 9NC from the cell cultures resulted in most nontumorigenic cells dividing, whereas tumorigenic cells continued to die after removal of 9NC. Taken together, the findings indicate a different response of nontumorigenic and tumorigenic breast cells to 9NC. PMID- 8453625 TI - Tamoxifen modulation of cisplatin sensitivity in human malignant melanoma cells. AB - Tamoxifen (TAM) markedly increases the response rate of malignant melanoma to treatment with cisplatin (DDP), carmustine, and dacarbazine, and we have previously reported that there is a highly synergistic interaction between TAM and DDP with respect to the cytotoxic effect against the human melanoma cell line T-289 (E. F. Mc Clay et al., Cancer Res., 52: 6790-6796, 1992). The mechanism underlying synergy was investigated by examining the effect of selection for either DDP or TAM resistance on the magnitude of the synergy quantitated by median effect analysis. The combination index at 50% cell kill was 0.26 +/- 0.02 (SD) for parental T-289 cells (indicating marked synergy), 0.54 +/- 0.14 for cells selected for low-level DDP resistance (indicating moderate synergy), and 1.39 +/- 0.20 for cells selected for low-level TAM resistance (indicating antagonism). Thus, factors that regulate DDP sensitivity have a moderate effect on reducing the DDP/TAM synergy, but determinants of TAM sensitivity have a major effect. The known biochemical effects of TAM include antagonism of estrogen at the estrogen receptor (ER) and inhibition of calmodulin and protein kinase C activity. T-289 cells contained undetectable amounts of ER by the dextran-coated charcoal assay and expressed only trace amounts of ER mRNA, and another more avid ER antagonist, droloxifene, failed to interact synergistically with DDP. N-(6 Aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), a potent calmodulin antagonist, failed to demonstrate synergy with DDP, and activation of protein kinase C, instead of interacting antagonistically with DDP, yielded synergy. TAM did not alter the cell cycle phase perturbation produced by exposure to DDP alone. We conclude that the synergy between TAM and DDP is not mediated by the effects of TAM on the ER, calmodulin, protein kinase C, or cell cycle regulation. However, the factors that determine cellular sensitivity to TAM also determine whether TAM interacts synergistically with DDP. PMID- 8453627 TI - In vitro cytotoxicity, cellular pharmacology, and DNA lesions induced by annamycin, an anthracycline derivative with high affinity for lipid membranes. AB - Annamycin (AN) is an anthracycline antibiotic with high affinity for lipid membranes which is being developed for clinical studies formulated in liposomes. We studied the in vitro cytotoxicity, cellular pharmacology, and DNA damage induced by AN in P388 cells sensitive and resistant to doxorubicin (DOX). AN was as cytotoxic as DOX against P388-sensitive cells and about 50 times more cytotoxic than DOX against P388-resistant cells (resistance index 5 for AN versus 250 for DOX). Cellular uptake of AN by sensitive cells was 2-3-fold higher than that of DOX. In resistant cells, cellular uptake of AN and DOX was approximately 65% and 30%, respectively, of the cellular uptake in sensitive cells. As a result, cellular uptake of AN by resistant cells was higher than uptake of DOX by sensitive cells. DOX was fully retained in sensitive cells while it was effluxed rapidly from resistant cells. In contrast, efflux of AN was similar in sensitive and resistant cells, thus suggesting that it is not mediated by P-glycoprotein. AN was more effective than DOX in inducing single DNA breaks, double DNA breaks, and DNA-protein cross-links, both in sensitive and resistant cells, although DNA damage was lower in resistant cells than in sensitive cells. DNA lesions induced by AN in resistant cells were similar to or greater than those induced by DOX in sensitive cells. These studies indicate that the lack of cross-resistance between DOX and AN appears to be related, at least in part, to the relatively higher cellular uptake of AN compared with DOX and is associated with the ability of AN to induce significant DNA damage in resistant cells. PMID- 8453628 TI - High-energy shock waves induce blood flow reduction in tumors. AB - We have studied the effect of extracorporeally applied high-energy shock waves (HESW) on blood flow in amelanotic melanomas (A-Mel-3). Two tumors were implanted in the dorsal skin of 21 Syrian golden hamsters. One of the tumors was treated with 200 HESW, and the other served as an intraindividual control. Mean blood flow in the whole tumor, or the tumor excluding necrotic areas, was quantitatively measured using autoradiography with iodo[14C]antipyrine at 30 min (n = 5), 1 h (n = 5), 3 h (n = 5), and 12 h (n = 6) after HESW treatment. As measured for the whole tumor, blood flow in the controls was 23.4 +/- 7.9 ml/100 g/min (median +/- SE) and thus in the range reported in the literature. Thirty min or 1 h after the application of HESW, tumor perfusion was reduced to 6 +/- 4% or 5 +/- 4% (median +/- SE) of the corresponding controls, respectively. Three h after treatment, perfusion increased slightly to 7 +/- 5% and after 12 h increased significantly to 55 +/- 25% of the corresponding controls. Values measured excluding the necrotic areas were higher in all groups. Temporary reduction of tumor perfusion after treatment with HESW was interpreted as a consequence of HESW-induced damage to tumor microcirculation. These effects should be taken into account for maximizing the therapeutic efficiency of HESW on tumors and for combining HESW treatment with other therapeutical modalities. PMID- 8453629 TI - Prolongation of drug exposure in cerebrospinal fluid by encapsulation into DepoFoam. AB - Prolonged maintenance of a therapeutic drug concentration in the cerebrospinal fluid is required for optimal treatment of leptomeningeal leukemia or carcinomatosis with cell cycle-specific antimetabolites. The pharmacokinetics of 1-beta-D-arabinofuranosylcytosine (ara-C) encapsulated into DepoFoam (Depo/Ara-C) was studied in six rhesus monkeys after intrathecal injection into the lumbar sac. Following a single 2-mg dose, the Depo/Ara-C concentration decreased biexponentially with initial and terminal half-lives of 14.6 and 156 h, respectively. The free drug concentration remained above the reported minimal cytotoxic level of 0.1 micrograms/ml (0.4 microM) for more than 672 h (28 days). In contrast, the half-life of ara-C following an intralumbar bolus dose of unencapsulated drug in a single animal was 0.74 h. A single intrathecal injection of Depo/Ara-C can maintain a therapeutic drug concentration in the cerebrospinal fluid for a very prolonged period. PMID- 8453630 TI - Intestinal intraepithelial lymphocytes bind to colon cancer cells by HML-1 and CD11a. AB - Human intraepithelial lymphocytes (IEL), predominantly CD8+ T-lymphocytes located between intestinal epithelial cells (EC), may represent the first-line immune defense against colon cancer. The mechanism by which IEL bind to the colon cancer line, DLD-1, was evaluated. A larger fraction of IEL than peripheral blood mononuclear cells bound to DLD-1 monolayers (25 +/- 16 versus 8 +/- 4% binding, P < 0.05). Binding increased when DLD-1 monolayers were incubated with interferon gamma but not with tumor necrosis factor-alpha. Similar numbers of IEL adhered to EC tumors, HT-29 and 5637, and the non-EC tumor, A375, but fewer bound to nonmalignant smooth muscle (HISM) and fibroblast (KD) lines (P < 0.01). Binding of IEL to DLD-1 was reduced by monoclonal antibodies to HML-1 and CD11a (47 +/- 9 and 26 +/- 13% inhibition, respectively) and was completely eliminated by both combined (93 +/- 4% inhibition). Anti-HML-1 also inhibited the binding of IEL to other EC tumors but did not affect binding to non-EC tumors or fibroblasts. To conclude, the binding of IEL to EC tumors is mediated by HML-1 and CD11a [A. I. Roberts, S. M. O'Connell, and E. C. Ebert. Binding of intraepithelial lymphocytes to colon cancer cells is mediated by HML-1 and LFA-1 (abstract). Gastroenterology, 102: A685, 1992]. PMID- 8453632 TI - ras mutations in 2-acetylaminofluorene-induced lung and liver tumors from C3H/HeJ and (C3H x A/J)F1 mice. AB - Previous studies have demonstrated mutagenic specificity of 2-acetylaminofluorene (AAF) in several strains of bacteria and mammalian cells. Examination of AAF induced B6C3F1 mouse liver tumor DNAs indicates a G-->T (or C-->A) transversion in the H-ras gene. In the present study, 6 mouse lung tumors [2 were from C3H/HeJ mice and 4 were from (C3H x A/J)F1 mice] and 20 C3H/HeJ mouse liver tumors induced by AAF were analyzed for the presence of activating mutations in the ras gene by utilizing polymerase chain reaction, single-strand conformation polymorphism, and direct DNA sequencing analysis. All of the lung tumors contained an activated K-ras protooncogene with an A-->T transversion at the second base of codon 61. The activating mutations in the H-ras gene were detected in 14 of 20 AAF-induced mouse liver tumors with 13 of 14 having a C-->A transversion at the first base of codon 61 and 1 of 14 having an A-->T transversion at the second base of codon 61. The selectivity of mutations in the ras oncogene observed in AAF-induced mouse lung and liver tumors, as compared to those in spontaneously occurring mouse lung and liver tumors, suggests that AAF may directly induce point mutations in the ras gene. The difference in the ras mutation spectra between lung and liver tumors induced by AAF indicates that AAF mutagenesis could be tissue-specific. PMID- 8453631 TI - Differential regulation of carcinoembryonic antigen and biliary glycoprotein by gamma-interferon. AB - Carcinoembryonic antigen (CEA), biliary glycoprotein (BGP), and non-specific cross-reacting antigen (NCA) are three closely related cell surface glycoproteins induced by gamma-interferon (IFN-gamma) in colonic epithelial cells. Maximal induction of CEA by IFN-gamma and tumor necrosis factor alpha (TNF-alpha) in the colon carcinoma cell line HT-29 occurs at 5-6 days with maximal secreted levels at 14 ng/ml for IFN-gamma and 20 ng/ml for TNF-alpha. Cell viability was reduced to 67% of controls for TNF-alpha and to 36% for IFN-gamma. Dose-response curves showed maximal induction of CEA at 500 units/ml for TNF-alpha and at 200 units/ml for IFN-gamma. Combinations of the two lymphokines revealed that the CEA induction effects were additive and the cytotoxicity effects were synergistic. Northern blot analysis of HT-29 cells treated with IFN-gamma and probed with specific probes for BGP, CEA, and NCA showed a 2-fold increase in mRNA level for BGP, and a greater than 10-fold induction for CEA and NCA. Similar results were obtained for the SW403 cell line, but in the case of the LS174T cell line, CEA mRNA levels remained constant before and after IFN-gamma treatment, while BGP and NCA mRNA levels increased by 2-5-fold. Polymerase chain reaction analysis of the four alternatively spliced transcripts of BGP revealed no differential induction of one transcript over another by IFN-gamma. A comparison of the kinetics of induction of the mRNA levels for BGP and CEA by IFN-gamma in the HT29 cell line revealed a half-time of < 6 h for BGP and 48 h for CEA. The induction of CEA mRNA was completely inhibited with either cycloheximide (protein synthesis inhibitor) or actinomycin D (RNA synthesis inhibitor), but the induction of BGP mRNA was superinduced by cycloheximide. The difference in the kinetics of induction and effect of cycloheximide on CEA and BGP mRNAs suggest that the two genes are regulated differently in the same cell line. We conclude that the regulation occurs mainly at the posttranscriptional level for CEA and involves mRNA stability. BGP regulation may be more complex, involving transcriptional and posttranscriptional regulation, and more closely resembles the regulation of MHC class II mRNA by IFN-gamma in epithelial cells. The mRNA stability effects may be mediated by the dramatically different sequences present in the 3'-untranslated regions of CEA and BGP. PMID- 8453633 TI - High mutation frequency in ras genes of skin tumors isolated from DNA repair deficient xeroderma pigmentosum patients. AB - Xeroderma pigmentosum (XP) patients are clinically characterized by a very high incidence of skin cancers on exposed skin, at an early age. XP cells in vitro are strongly deficient in excision-repair and highly mutagenized by UV light. We were, therefore, interested in measuring mutation frequency and in determining mutation spectra in patients' tumors exposed to UV lesions. We chose to look at oncogene activation in skin tumors with the idea that more mutations, particularly of the ras gene family, would be found in XP tumors where lesions remain unrepaired compared to normal individuals. Our results clearly show that more than a 2-fold significantly higher mutation frequency (50%) of the ras genes was found in XP in contrast to control tumors (22%). The majority of the mutations were found at codon 12 of all three ras genes with a preponderance for N-ras in XP samples. The mutation spectra indicate that all mutations found were located opposite pyrimidine-pyrimidine sequences which represent a hot spot for UV-induced DNA lesions. Most of the mutations were of the type expected from studies performed in vitro with model systems. This high mutation frequency in XP was accompanied by a very high level of Ha-ras and c-myc gene amplification and rearrangement. All these data are consistent with a fundamental role of unrepaired UV-induced DNA lesions as an initiating event in human skin tumors on exposed parts of the body. PMID- 8453634 TI - Transforming growth factor-alpha production and autoinduction in a colorectal carcinoma cell line (DiFi) with an amplified epidermal growth factor receptor gene. AB - The DiFi colorectal carcinoma cell line, derived from a patient with familial adenomatous polyposis, was examined for gene expression and production of the autocrine growth factor transforming growth factor alpha (TGF-alpha) and for epidermal growth factor receptor (EGFR) gene expression and gene copy number. DiFi cells expressed TGF-alpha transcripts as identified on Northern (RNA) blots. Addition of TGF-alpha (10 ng/ml) or EGF (10 ng/ml) to DiFi cell cultures (lacking EGF or serum) up-regulated DiFi cell basal TGF-alpha mRNA levels, suggesting that autoinduction of TGF-alpha occurs in these cells. DiFi cell cultures in log phase growth secreted measurable amounts of TGF-alpha (347 pg/10(6) cells/24 h) into their culture medium, as determined by radioimmunoassay. DiFi cells showed strong overexpression of the EGFR gene on Northern blots relative to three other colon cancer cell lines examined. Immunoperoxidase staining showed enhanced EGFR expression in a cell subpopulation among the original (uncultured) ascitic fluid cells from which the DiFi cell line was established. This cell subpopulation was observed to expand dramatically between passages 1 and 25. Immune complex kinase assay of DiFi cells showed that EGFR were functional as determined by their ability to autophosphorylate. The EGFR gene in these cells was not found to be rearranged or genetically altered using Southern blot analysis. Dot blot analysis of DiFi cell DNA revealed EGFR gene amplification in the range of 60-80 copies/cell, which is approximately twice the copy number seen in A-431 epidermoid carcinoma cells. To our knowledge DiFi cells represent the first example of EGFR gene amplification in a colorectal adenocarcinoma. Because DiFi colorectal cancer cells uniquely show production and auto-induction of TGF-alpha in addition to amplification and overexpression of the EGFR gene, these cells represent a valuable tool for studying the role(s) of the EGFR in the regulation of tumor cell growth. PMID- 8453635 TI - Somatic p53 mutations in human breast carcinomas in an Icelandic population: a prognostic factor. AB - Mutations in the p53 gene are among the most common genetic changes in human carcinomas. They have been found in many tumor types including colon, lung, and breast. We have used constant denaturant gel electrophoresis in order to screen samples from 109 breast carcinomas for mutations in four conserved regions, exons 5, 7, and 8, of the p53 gene. Samples were also analyzed for allelic loss of the p53 gene and of markers more distal on chromosome 17 p. Mutations were confirmed by DNA sequencing. Mutations were found in 18 of the 109 samples (16.5%). Loss of heterozygosity at 17p was detected in the majority of informative mutated cases. All cases were also screened for germ line mutations, but none were found. The results obtained were analyzed with respect to clinical parameters and prognosis. There was a significant association between p53 mutation and low content of estrogen receptor protein in the tumors (P = 0.01). An association with poor prognosis was strongly indicated by mortality rates that were 37.5% among the patients with p53 mutation and 9.4% for the control group (mean follow up, 32 months). P53 mutation was found to be the strongest negative factor against survival in a covariate survival analysis (P = 0.001). PMID- 8453636 TI - Ultraviolet-induced cyclobutane pyrimidine dimers are selectively removed from transcriptionally active genes in the epidermis of the hairless mouse. AB - This study describes the induction and repair of UV-induced cyclobutane pyrimidine dimers (CPD) in transcriptionally active and inactive genes in the epidermis of the hairless mouse. Mice were exposed to a single dose of 2000 J/m2 ultraviolet B and kept in darkness for up to 24 h. The CPD frequency was measured in the transcriptionally active hypoxanthine-guanine phosphoribosyltransferase gene, the adenosine deaminase gene, the inactive c-mos protooncogene, and the haptoglobin gene using the CPD-specific enzyme T4 endonuclease V. Sixty % of the CPD was removed from the active genes during the first 4 h, after which no further repair took place up to 24 h. In contrast, the inactive genes did not show any removal of CPD. Assuming that the rate of repair in the c-mos and haptoglobin genes is representative for the repair rate in the genome overall, these results suggest only marginal repair of UV-induced CPD in the mouse epidermis in vivo. The selective repair of active genes in the epidermis of mice resembles that of rodent cells in culture and shows the biological relevance of repair studies performed with cultured rodent cells in vitro. PMID- 8453637 TI - p53 mutations selected in vivo when mouse mammary epithelial cells form hyperplastic outgrowths are not necessary for establishment of mammary cell lines in vitro. AB - Breast cancer is a consequence of multiple alterations occurring over a long period of time. Genetic changes in early stages of tumorigenesis have not been defined. A recently developed murine system permits the study of mammary preneoplastic cells in vivo and in vitro (F. S. Kittrell et al., Cancer Res., 52: 1924-1932, 1992). To assess the potential role of p53 mutations in early stages of breast cancer, the status of p53 was determined in a series of mouse mammary epithelial cell lines which give rise to preneoplastic outgrowths (hyperplastic alveolar nodules) when transplanted into cleared mammary fat pads of syngeneic mice. Protein stability and conformation were analyzed using immunoprecipitations and immunochemical assays; p53 transcripts were sequenced using a polymerase chain reaction approach. The parental cell lines (FSK lines) showed no evidence of p53 alterations at either the protein or the nucleic acid level, indicating that p53 mutations are not essential for the establishment of mammary epithelial cell lines in vitro. In contrast, cell lines (TM lines) derived from hyperplastic alveolar nodule outgrowths induced by FSK cells expressed only mutant p53 genes. The mutation in one outgrowth cell line (TM-2H) resulted in the loss of p53 protein synthesis, whereas two other outgrowth lines (TM-3, TM-4) overexpressed mutant p53 protein. Mutation of p53 appears to correlate with preneoplastic growth in vivo. Although it is not clear if the mutations occur before or after transplantation of cells in vivo, there appears to be a pronounced growth advantage in the mammary gland for cells expressing mutant p53. PMID- 8453638 TI - Transcriptional activation of the mouse mdr3 gene coincides with the appearance of novel transcription initiation sites in multidrug-resistant P388 tumor cells. AB - In independently derived drug-resistant sublines of the mouse lymphoid tumor P388, multidrug resistance is associated with the exclusive overexpression of the mdr3 gene. In P388/VCR cells, mdr3 overexpression occurs in the absence of gene amplification, while in P388/ADM-2 cells overexpression is associated with mdr3 gene amplification. The mechanism underlying mdr3 overexpression in these cells was investigated. Measurement of the rate of transcription by nuclear "run-on" assays showed that increased mdr3 expression in P388/VCR cells was caused by transcriptional activation of the gene. Analysis of the 5' end of mdr3 mRNA transcripts by primer extension indicated that in P388/VCR cells, these mRNAs extended approximately 200 nucleotides upstream exon 2, about 60 nucleotides longer than their counterparts expressed in normal tissues from the known transcription start site of the gene (TS1). Northern blotting experiments using discrete exon and intron probes derived from the 5' end of the gene near TS1, together with ribonuclease protection using a complementary RNA probe from the same region, demonstrated that transcriptional activation in P388/VCR cells occurred from a novel transcription start site named TS3, located either upstream of TS1 or within intron 1 at a site immediately upstream a novel exon. In P388/ADM-2 cells, Northern blotting and ribonuclease protection identified overexpressed mdr3 mRNAs initiating near TS1 and a large partially spliced mdr3 mRNA species initiating upstream of TS1 at a novel initiation site designated TS2. Therefore, mdr3 overexpression in independently derived multidrug-resistant isolates of P388 cells is associated with the appearance of novel transcription start sites in the gene and novel sequences at the 5' end of the overexpressed mRNAs. PMID- 8453639 TI - Multiple mechanisms of tumorigenesis in E mu-myc transgenic mice. AB - Transgenic mice bearing a c-myc oncogene under control of the immunoglobulin heavy chain enhancer (E mu-myc mice) reproducibly develop and die from tumors of the B lymphocyte lineage (J.M. Adams, A.W. Harris, C.A. Pinkert, L.M. Corcoran, W.S. Alexander, S. Cory, R.D. Palmiter, and R.L. Brinster, Nature (Lond.), 318: 533-538, 1985; W.Y. Langdon, A. W. Harris, S. Cory, and J.M. Adams, Cell 47: 11 18, 1986; A.W. Harris, C.A. Pinkert, M. Crawford, W.Y. Langdon, R.L. Brinster, and J.M. Adams, J. Exp. Med., 167: 353-371, 1988; reviewed in S. Cory and J.M. Adams, Annu. Rev. Immunol., 6: 25-48, 1988). Analysis of lymphocytes obtained by serial sampling of peripheral blood from individual hemizygous (E mu-myc/0) and homozygous (E mu-myc/E mu-myc) transgenic mice indicates that proliferation in the original host and transplantability into histocompatible recipients are distinct properties that can be acquired independently and in either order. These two types of transgenic mice differ in that homozygous mice have about one-fourth the life span of hemizygous mice and develop polyclonal, non-transplantable tumors in comparison to the oligoclonal, highly transplantable malignancies seen in hemizygous animals. In conclusion, the overall concept of malignancy is best viewed as an aggregate of the separable parameters of cellular proliferation, clonality, tissue invasiveness, metastasis, and (experimental) transplantability. The E mu-myc transgenic mouse represents an attractive model in which to investigate the multistep nature and alternative pathways of tumorigenesis. PMID- 8453640 TI - Chromosome 12 breakpoints are cytogenetically different in benign and malignant lipogenic tumors: localization of breakpoints in lipoma to 12q15 and in myxoid liposarcoma to 12q13.3. AB - Cytogenetic study of short-term cultures from 10 adipose tissue tumors (eight lipomas, one myxoid liposarcoma, and one mixed liposarcoma) have revealed clonal chromosome abnormalities in seven cases. In both malignant tumors, translocation (12;16) was the sole aberration, and in the mixed liposarcoma, the breakpoints could be sublocalized to bands 12q13.3 and 16p11.2, thus confirming findings of Eneroth et al., Cancer Genet. Cytogenet., 48: 101-107, 1990. Three lipomas displayed predominantly normal karyotypes; in a fourth case, the karyotype 44,XX, 6,der (7)t(6;7)(p21.3-22;p22)ins(7)(p22q11.2q22),-13 was found. Four remaining lipomas were characterized by structural rearrangements of chromosome 12. We were able to achieve high resolution banding patterns in two tumors with translocations (3;12)(q28;q15) and (1;2;12)(p36.;q13;q15). In both of these cases, the chromosome 12 breakpoint could be unequivocally assigned to band q15. Similarly, band 12q15 was also rearranged in two other lipomas with translocations (12;14)(q15;q32) and (12;20)(q15;q13.1). Our results support the hypothesis that the chromosome 12 breakpoint in lipomas is located more distally than the breakpoint in myxoid liposarcomas and some other soft-tissue malignant neoplasms and that it is cytogenetically identical with breakpoints detected in such benign tumors as uterine leiomyoma and pleomorphic adenoma of the salivary gland. PMID- 8453641 TI - Discordant p53 gene mutations in primary head and neck cancers and corresponding second primary cancers of the upper aerodigestive tract. AB - Patients with primary head and neck malignancies have a 3-7% yearly incidence of second primary cancers. It is thought that these second primary cancers arise independently following exposure to a common carcinogen by a process that has been called field cancerization. Since mutations in the p53 tumor suppressor gene represent a genetic alteration occurring during the evolution of premalignant lesions to malignancies of the upper aerodigestive tract, we analyzed mutations in the p53 gene of patients with cancer of the head and neck who developed second primary tumors of the upper aerodigestive tract epithelium to test the field cancerization hypothesis. DNA was extracted from primary head and neck cancers and second primary cancers of 31 patients. DNA from exons 5-8 of the p53 gene was analyzed by the single strand conformation polymorphism technique to identify the locations of the mutations in different regions of the gene. DNA from 6 patients was also sequenced by the chain termination method to confirm the presence of mutations and determine the base substitutions. Twenty-one of the 31 patients had 1 or more p53 mutations. In all 21 cases the genetic lesions were discordant such that the presence or location of the mutations in the initial primary cancer differed from those of the second and third primary cancers. In each of the five patients with mutations in both primary tumors, the mutations occurred in different regions of the p53 gene. Of the other 16 patients, 8 had a p53 mutation in the first primary but not the subsequent primary cancer and the other 8 had no mutation in the initial primary but did have a mutation in subsequent primary cancers. Sequencing confirmed the single strand conformation polymorphism analysis and showed that 73% of the mutations were transitions. The discordant p53 mutations in second primary cancers arising in patients with primary epithelial cancer of the upper aerodigestive tract suggest that these cancers arise as independent events. These observations provide the first demonstration of a molecular basis for field cancerization effects in cancers of the upper aerodigestive tract. PMID- 8453642 TI - Altered chromosomal methylation patterns accompany oncogene-induced transformation of human bronchial epithelial cells. AB - Abnormal methylation of CpG island sequences on chromosomes 11p and 17p, and tumor phenotype-associated differential methylation of chromosome 3p loci have been described in human lung tumors (S.B. Baylin, J.W.M. Hoppener, A. de Bustros, P.H. Steenbergh, C.J.M. Lips, and B. D. Nelkin, Cancer Res., 46: 2917-2922, 1986; M. Makos, B.D. Nelkin, M. I. Lerman, F. Latif, B. Zbar, and S.B. Baylin, Proc. Natl. Acad. Sci. USA, 89: 1929-1933, 1992; A. de Bustros, B. D. Nelkin, A. Silverman, G. Ehrlich, B. Poiesz, and S. B. Baylin, Proc. Natl. Acad. Sci. USA, 85: 5693-5697, 1988). Using an in vitro model of lung tumor progression, we now show that these aberrant methylation patterns occur at different stages during cellular immortalization and oncogene-induced neoplastic transformation of normal human bronchial epithelial cells (NHBE). The CALC1 CpG island locus on chromosome 11p15.4 was essentially unmethylated in NHBE and simian virus 40 T-antigen immortalized NHBE (BEAS-2B cells) but became de novo methylated in 5 of 6 BEAS-2B derived cell lines that were transfected or infected with various oncogenes and in a spontaneously neoplastically transformed subline of BEAS-2B cells. By contrast, an additional CpG island locus, pYNZ22, at 17p13.3 became fully methylated following the immortalization of NHBE and was not further changed by oncogene-induced transformation. Finally, at a non-CpG island locus pYNZ86.1 on chromosome 3p14, different tumor phenotype-associated methylation patterns became apparent only after passage of the turmorigenic oncogene-transformed bronchial epithelial cell lines in athymic nude mice. Whereas cell lines derived from tumors with a non-small cell lung carcinoma-like phenotype were significantly hypomethylated relative to their parental cell lines, a cell line derived from a tumor with a more small cell lung carcinoma-like phenotype retained the methylation status of its parental cell line. The data indicate that altered DNA methylation patterns, including the de novo methylation of normally unmethylated CpG island sequences and demethylation of nonisland sequences, arise at different stages during immortalization and oncogene-induced neoplastic transformation of bronchial epithelial cells. These findings suggest that DNA methylation abnormalities accompany, or may play a role in, the genetic changes that occur during lung tumor progression. PMID- 8453643 TI - E-cadherin expression in primary and metastatic gastric cancer: down-regulation correlates with cellular dedifferentiation and glandular disintegration. AB - Expression of the epithelial cell adhesion molecule E-cadherin in primary and metastatic gastric carcinoma was examined using immunohistochemical analyses. Compared to normal mucosa, 92% of the primary tumors (n = 60) showed reduced E cadherin expression, suggesting that down-regulation of this cell adhesion molecule is a common early event in gastric tumorigenesis. No significant correlation was found between E-cadherin expression and tumor diameter, lymphatic vessel invasion, Borrmann classification, lymph node status, or manifest metastases. Although advanced tumors (tumor stage 3/4) showed a loss of E cadherin-positive cells (< or = 50% cells/lesion, P = 0.0168), the most significant correlation was observed between low E-cadherin expression and cellular dedifferentiation (grading 3/4, P = 0.0001) and disintegration of tissue architecture (Lauren and WHO classifications, P = 0.0001). Low E-cadherin expression (< or = 50% cells/lesion) was associated with tumor recurrence (P = 0.0013) and mortality (P = 0.0246). E-cadherin expression in metastatic lesions (n = 58) also correlated with the degree of glandular differentiation (P = 0.0001). Significant correlation (rs = 0.686) was observed between E-cadherin expression in primary and metastatic lesions from individual patients (n = 39). However, while metastases derived from E-cadherin-negative tumors remained negative, those originating from E-cadherin-positive tumors frequently demonstrated increased levels of expression. Evaluation of multiple metastases in 11 patients revealed uniformly strong E-cadherin expression in liver metastases, suggesting a possible regulatory role of the microenvironment. PMID- 8453644 TI - Expression of E-cadherin cell adhesion molecules in human breast cancer tissues and its relationship to metastasis. AB - E-cadherin (E-cad) is a subclass of the cadherin family that plays a major role in maintenance of intercellular junctions in epithelial tissues. In order to explore the correlation between the expression of E-cad and cancer invasion and metastasis in vivo, we performed an immunohistochemical examination for E-cad expression in 120 patients with breast cancer using our specific anti-E-cad monoclonal antibody. In noncancerous epithelial cells, E-cad was strongly expressed on cell-cell boundaries, whereas various staining patterns were observed in tumors. Of these 120 tumors, 56 (47%) showed Pr type expression of E cad, and 64 (53%) showed Rd type or negative expression. We found significant correlations between E-cad expression and clinicopathological features. The frequency of Rd type was significantly higher in invasive ductal carcinomas (58%, 56 of 97) and poorly differentiated carcinomas (84%, 21 of 25) than in noninvasive and well-differentiated carcinomas. Furthermore, a high frequency of Rd type was detected in the following advanced tumors: T3,4 tumors, 71% (22 of 31); tumors with extensive lymph node metastasis, 74% (29 of 39); and tumors with distant metastasis, 86% (19 of 22). These values were significantly higher compared with their counterparts. The expression of epidermal growth factor receptor tended to be positive in E-cad-positive tumors. However, no significant relationship was seen among E-cad expression, menopausal status, hormone receptor status, and DNA ploidy pattern. These results suggest that the reduction of E-cad expression may play an important role in invasion and metastasis of human breast cancer. PMID- 8453645 TI - Protein interaction of retinoblastoma gene product pRb110 with M(r) 73,000 heat shock cognate protein. AB - Both the tumor suppressor gene products, the retinoblastoma sensitivity gene product pRb110 and p53, are found in oligomer complexes with the oncogene products of the DNA tumor viruses. It has been demonstrated that p53 binds to the M(r) 70,000 heat shock protein family. However, the protein association of pRb110 with the M(r) 70,000 heat shock protein family is not yet known. We analyzed the immunoprecipitates made with TYK-nu human ovarial carcinoma cell lysate and anti pRb110 or anti-heat shock protein monoclonal antibodies. In this paper, we demonstrate that pRb110 is associated with the M(r) 73,000 heat shock cognate protein, but not with the M(r) 72,000 heat shock protein. This selective protein association was also detected in HeLa cervical carcinoma cells. Furthermore, the protein complexes of the M(r) 73,000 heat shock cognate protein and pRb110 were dissociated with the presence of ATP, but not with ADP and the nonhydrolyzable ATP analogue, ATP gamma S. This indicates that the dissociation is dependent on the ATP hydrolysis. These data may suggest an as yet undefined important role of M(r) 73,000 heat shock cognate protein in the cell growth control in collaboration with pRb110. PMID- 8453646 TI - Expression of Sialyl-Tn antigens in normal squamous epithelium, dysplasia, and squamous cell carcinoma in the esophagus. AB - Two monoclonal antibodies, TKH2 and B72.3, directed toward the Sialyl-Tn antigen (SA 2, 6GalNAc alpha-O-Ser/Thr), were examined immunohistochemically to analyze the expression of these antigens in 20 areas of normal squamous epithelium, 12 lesions of dysplasia, and 86 cases of squamous cell carcinoma including 32 with superficial carcinoma in the esophagus. No expression of TKH2 or B72.3 was found in the normal squamous epithelium. Among the 12 lesions of dysplasia only one expressed TKH2. In carcinoma the expression of TKH2 and B72.3 was found in 40 (47%) and 21 (24%) of the 86 carcinomas, respectively; however, the number of positive malignant cells with TKH2 and B72.3 totaled less than half that in the tissue, and no relationship was found between either prognosis or lymph node metastasis and the expression of Sialyl-Tn antigen. These results indicate that Sialyl-Tn antigen appears in the process of malignant transformation or tumor progression in esophageal squamous cell carcinoma; however, the positive expression of Sialyl-Tn antigen was not directly connected to either prognosis or lymph node metastasis. PMID- 8453647 TI - [Endocrine function of the cardiovascular system]. AB - The cardiovascular system has in addition to it haemodynamic role also an important endocrine function. It produces a number of humoral substances which are either released into the circulation and exert a systemic endocrine effect (e.g. the atrial natriuretic factor from the atria) or act at the site of their genesis. This autocrine or paracrine action is typical above all for substances formed in the endothelium and vascular wall (endothelin, endothelium-derived relaxation factor, prostaglandins, prostacyclines, renin-angiotensin cascade etc.). Cardiovascular substances influence by their action markedly the general and organ haemodynamics, the volume and pressure homeostasis the development and regression, of cardiac hypertrophy and vascular walls, as well as thrombogenesis and atherogenesis. They participate thus in a significant way in physiological regulations and pathological processes in the organism. PMID- 8453648 TI - [Insulin secretion and sensitivity in middle-aged men in the initial stages of type II diabetes mellitus (evaluated by the "minimal model" method]. AB - The objective of the work was to test the minimal model method based on computer evaluation of parameters (blood sugar level, insulin blood level) obtained during the intravenous glucose tolerance test with frequent collection of samples, when examining the insulin glucose homeostasis in patients in the initial stage of type II diabetes. The authors examined a control group of 8 healthy men, mean age 43.6 years, BMI 24.7 and a group of 7 men with type II diabetes, mean age 46.7 years, BMI 31.37. Indexes (phi 1 and phi 2--the first and second stage of insulin secretion, SG-glucose efficiency, SI-insulin sensitivity) were obtained by evaluation of the results, using a programme for a personal computer PC AT. In men of the control group the authors recorded the following values: phi 1 5.80 +/ 1.26 microU/ml x min/mg/dl, phi 2 6.43 +/- 5.15 microU/ml x min-2/mg/dl, SG 0.016 +/- 0.010 min-2. Diabetic patients were divided with a regard to the first stage of insulin secretion into two groups: the first one (n = 4) comprises those where the first stage is minimal (phi 1 = 0.80 +/- 0.68 microU/ml x min/mg/dl, phi 2 = 33.41 +/- 19.06 microU/ml x min-2/mg/dl, in the second group are those (n = 3) where the first stage of insulin secretion is maintained phi (1 12.23 +/- 5.51 microU/ml x min-2/mg/dl, phi 2 7.77 +/- 4.98 microU/ml x min-2/mg/dl). The second stage of insulin secretion in subjects of the first group is, as compared with controls, significantly higher (p < 0.05). PMID- 8453649 TI - [Changes in plasma renin and aldosterone after parathyroidectomy in patients with hyperparathyroidism]. AB - The plasma renin activity and its changes after parathyroidectomy indicate a preserved internal secretory renal function in dialyzed patients. The PRA values before parathyroidectomy are not unequivocally related to the blood pressure reading. After parathyroidectomy during the initial months the renin and aldosterone plasma levels decline in patients with secondary and primary HPT (p < 0.001), the urinary Na/K quotient rises in primary HPT (p < 0.05) and the systemic blood pressure declines in dialyzed patients with secondary HPT (p < 0.001). The findings suggest relations between the two hormonal systems during hyperparathyroidism and in the early stage after parathyroidectomy. Parathormone probably stimulates renin secretion. After a prolonged time interval following operation the parathormone levels in the blood steam reach normal levels and the same probably applies to intracellular calcium in cells of the iuxtaglomerular apparatus along with PRA. PMID- 8453650 TI - [Albuminuria after acute oral administration of proteins in patients with renovascular hypertension]. AB - In a group of 19 patients with renovascular hypertension the effect of a morning snack comprising meat (1 g protein per 1 kg body weight) on urinary albumin excretion was assessed. Concurrently the plasma creatinine concentration (Pcr) was examined which varied between normal and 260 mumol/l and the creatinine clearance (Ccr). After administration of an acute protein load the mean Ccr value increased by 23%. The albumin excretion, however, did not change substantially, as compared with the previous collection period (mean 17 and 18 micrograms/min). Microalbuminuria was recorded in 31% of the patients and its prevalence was directly related to the increasing Pcr value. The results revealed that an acute protein load did not increase albuminuria although the rise of Ccr was significant. The variability of albumin excretion in the course of the day is, however, influenced also by other factors and for assessment of microalbuminuria therefore examination of 24-hour urine samples should be preferred. PMID- 8453651 TI - [Does a hypertensive reaction to dynamic exercise imply an increased risk of developing essential hypertension?]. AB - Early diagnosis of essential hypertension, preferably in the pre-hypertensive stage, is very important for the prognosis of affected subjects. Based on sporadic information in the literature it seems that people who are normotensive at rest but have an exaggerated hypertensive reaction to exercise have a greater risk of developing essential hypertension in future. The authors selected from protocols of ECG exercise tests a group of subjects with normal blood levels at rest but an exaggerated hypertensive reaction to a dynamic exercise. The control group was formed by people with a normal pressure reaction to a exercise the control group was matched as regards age, sex and basic anthropometric parameters. After a mean period of 7.8 years (range 5-10 years) it was revealed that while in the control group hypertension was manifested in 10%, in the group with an exaggerated hypertensive reaction to an exercise it was manifested in 33.3%. The mean original blood pressure readings at rest were significantly higher in people with a normal blood pressure reaction to an exercise and this difference persisted also at the end of the investigation. An exaggerated hypertensive reaction to a dynamic exercise is one of the prognostic factors for the development of essential hypertension and should be a reason for follow-up. PMID- 8453653 TI - The bovine tubouterine junction: general organization and surface morphology. AB - The bovine tubouterine junction is composed of three parts (terminal tubal segment, transition region proper, uterine apex) and follows a sigmoidal course displaying a tubal and an uterine curvature. In the terminal tubal segment, 4-8 primary longitudinal folds and a system of lower secondary folds, ridges and chords project into the centrally located lumen. The transition region proper possesses a slit-like lumen because of the existence of a thick mucosal pad containing the first uterine glands. The longitudinal primary folds of the tube broaden, flatten and start to diverge when they reach the transition region proper. The mucosal pad and broadened folds are heavily vascularized. A system of lateral outpocketings with blind ends pointing in an ampullary direction develops between the primary and secondary folds, the ridges and chords of the terminal tubal segment and transition region proper. From the bottom of these outpocketings, short tubulo-alveolar crypts originate. The mucosa of the uterine apex forms low transversal ridges. The musculature of the bovine tubouterine junction is divided into a continuous circular or spiral intermediate layer, flanked by inner and outer longitudinal layers. The outer longitudinal layer is incomplete in the terminal tubal segment but increases in thickness to form a continuous stratum in the uterine apex. An inner longitudinal layer occurs only in the terminal tubal segment where it is best developed in the bases of the primary longitudinal folds. The simple columnar surface epithelium of the tubouterine junction contains ciliated and non-ciliated cells. The former undergo cyclical changes, and increase during estrus and postestrus. During proestrus, groups of non-ciliated cells display bulbous apical protrusions. During proestrus and estrus, circumscribed epithelial lesions expose the underlying basal lamina. PMID- 8453654 TI - Ultrastructure and morphometry of testicular Leydig cells and the interstitial components correlated with testosterone in aging rats. AB - The ultrastructure of testicular interstitium in young and aged adult rats was analysed using morphometric methods, and the plasma testosterone concentration was measured. With increasing age there was an augmentation in the volume of collagen fibrils in the intercellular matrix and in blood vessels. During the aging process (approximately two years) the average volume of the Leydig cell decreased from 1364 microns 3 to 637 microns 3, but the number of Leydig cells in paired testes increased from 53 x 10(6) to 113 x 10(6). The absolute volume of smooth surfaced endoplasmic reticulum (SER) per Leydig cell amounted in aged rats to 78% of that in young adult rats. The total amount of SER in paired testes increased by 62% with aging. The present analysis suggests that the ability of SER to maintain peripheral testosterone concentration decreases with age. In young adult rats the absolute volume of peroxisomes per Leydig cell correlated significantly with the concentration of testosterone in blood and also with the absolute volume of SER per Leydig cell. These results combined with ultrastructural observations of close apposition of peroxisomes and SER suggest that peroxisomes have a role in testosterone secretion by Leydig cells. PMID- 8453655 TI - Differences between adrenomedullary adrenaline and noradrenaline cells: quantitative electron-microscopic evaluation of their differential cellular association with supporting cells. AB - Quantitative differences in cellular association of adrenomedullary chromaffin cells with other types of cells, mainly supporting cells, were studied. Adrenaline (A) and noradrenaline (NA) cells were compared. Electron micrographs (12000 x) of profiles of A and NA cells, bordering against other types of cells, were used for quantitative evaluation. Supporting cells constituted the majority of the non-chromaffin cell types. Occurrence frequencies of chromaffin cells contiguous with other types of cells were: (1) higher for A cells (68.9%, 199/289) than for NA cells (11.0%, 34/309) in case of small contact regions (chi 2-test: P < 0.001), and (2) higher for NA cells (68.3%, 211/309) than for A cells (9.7%, 28/289) in case of extended contact regions (P < 0.001). In conclusion, the extent of cellular association with supporting cells was remarkably lower in A cells than in NA cells. Such an arrangement is likely to be appropriate for the extensive, homogeneous control and amplified response characteristic of A cells, and for the close range, complex control and more diverse responses characteristic of NA cells. PMID- 8453656 TI - Seasonal changes in the hypothalamic vasopressinergic system of a wild Sahelian rodent, Taterillus petteri. AB - Seasonal variations in the immunoreactivity of vasopressinergic perikarya in the paraventricular (PVN), supraoptic (SON) and suprachiasmatic nuclei (SCN), and in the labelling of vasopressinergic fibres in the internal zone of the median eminence were studied in Taterillus petteri, a rodent that is found in the north Burkina Faso (formerly Upper Volta). In this region, there are four seasonal climatic combinations: the humid and hot, humid and cold, dry and cold, and dry and hot seasons. In the dry hot season, the rodents experience phases of torpor (adaptation to dryness). Immunoreactivity of the PVN and SON is highest during the dry cold season. Labelling is intense during the dry hot and humid hot seasons, and is at its lowest during the humid cold season. In the SCN, labelling of the perikarya is only dense during the dry hot season, whereas for the rest of the year, the immunoreactivity is weak or undetectable. The pattern of immunoreactive variations of vasopressin-positive fibres located in the internal zone of the median eminence is similar to those of vasopressinergic perikarya in the PVN and SON. These results suggest that there is an association between: (1) seasonal modifications in the immunoreactivity of PVN and SON vasopressinergic perikarya and vasopressinergic fibres of the internal median eminence, and (2) climatic conditions, water metabolism, behavioural activity and diet. It is not possible to establish a correlation between seasonal variations in water availability and fluctuations in the labelling of vasopressinergic perikarya in the SCN. However, labelling is intense when the animals are in torpor during the dry hot season. PMID- 8453657 TI - Transformation of fetal secondary cartilage into embryonic bone in organ cultures of human mandibular condyles. AB - Mandibular condyles of human fetuses, 14-21 weeks in utero, were kept in an organ culture system for up to 60 days. After 6 days in culture, the cartilage of the mandibular condyle appeared to have maintained its inherent structural characteristics, including all its various layers: chondroprogenitor, chondroblastic, and hypertrophic. After 12 days in culture, no chondroblasts could be seen; instead, the entire cartilage was occupied by hypertrophic chondrocytes. At the same time, the mesenchymal cells in the vicinity of the chondroprogenitor zone differentiated into osteoblast-like cells that produced type I collagen. The progenitor cells were still actively incorporating 3H thymidine. The newly formed osteoid-like tissue lacked both metachromatic reactivity and a response to antibodies against chondroitin sulfate. Instead, the tissue reacted positively for osteocalcin (bone gla-protein). The process of new bone formation further progressed and, by the 20th day in culture, the new bone reacted positively for type I collagen, osteonectin, and to a lesser extent for chondroitin sulfate. The osteoid also underwent mineralization as revealed by both the von Kossa stain and vital staining with tetracycline. The above feature appeared even more intense in 40-day-old cultures. After 60 days, the newly formed bone contained osteoblasts and osteocytes, whereas the extracellular matrix revealed a high degree of matrix polarization. The results of the present study recapitulate findings reported for organ cultures of mice mandibular condyles. However, the in vitro process of de novo bone formation in human specimens requires a 6-fold longer culture time than that needed for mice condyles. PMID- 8453658 TI - Ultrastructural radioautographic analysis of neurogenesis in the hypothalamus of the adult frog, Rana temporaria, with special reference to physiological regeneration of the preoptic nucleus. I. Ventricular zone cell proliferation. AB - The localization and fine structure of proliferating cells in the hypothalamic preoptic area were studied by light- and electron-microscopic radioautography 1-2 h following single application of 3H-thymidine to adult Rana temporaria taken from their natural habitat in the spring and autumn. 3H-thymidine uptake by proliferating cells was much more pronounced in frogs caught in May/June, i.e., a month after the breeding period (labeled cells represent about 10% of the total ventricular zone cell population), compared to animals caught in mid-September, when it was very low. In both 3H-thymidine treatment groups the vast majority of labeled cells are found exclusively within the preoptic recess ventricular zone. With regard to ultrastructure, it contained proliferating cells of at least 4 types, ranging from immature forms (bipolar stem cells) to more differentiated elements (tanycyte-like ependymoblasts, "classical" ependymoblasts). All of them showed label over their nuclei indicating that these cells are capable of DNA synthesis and mitosis. The possible role of the preoptic recess ventricular zone as a source of precursor cells for new peptidergic neurosecretory cells, conventional neurons and glial cells in the hypothalamic preoptic area of the adult frog is discussed. PMID- 8453659 TI - Ultrastructural radioautographic analysis of neurogenesis in the hypothalamus of the adult frog, Rana temporaria, with special reference to physiological regeneration of the preoptic nucleus. II. Types of neuronal cells produced. AB - Light- and electron-microscopic radioautography was used to identify the newly formed neuronal cells in the hypothalamic preoptic area of the frog. Adult Rana temporaria that had been caught in May/June received repeated 3H-thymidine injections and were sacrificed 30 days later. Heavily labeled cells were found in 1-micron plastic coronal sections of the preoptic area and then analysed in electron-microscopic radioautographs of neighbouring thin sections. The cells were identified as newly generated by the presence of 3H-thymidine label over the nucleus. All frogs showed considerable numbers of new peptidergic neurosecretory cells, small conventional neurons, and glia in the preoptic area. Some new ependymally located cells contacting the cerebrospinal fluid displaying ultrastructural characteristics of monoaminergic cells were also revealed. We conclude that prominent ventricular neurogenesis normally exists in the intact adult frog hypothalamus. The birth of small hypothalamic neurons seems to represent a case of sustained growth leading to a net increase in neuron numbers without loss. Conversely, the birth of large peptidergic neurosecretory cells, in which the increased secretory activity often leads to natural death of some cells, is considered as a neuronal replacement phenomenon, referred to as physiological regeneration of the magnocellular preoptic nucleus. The possible significance of this phenomenon in adult Anamnia is discussed. PMID- 8453652 TI - Calcium-binding proteins: selective markers of nerve cells. PMID- 8453660 TI - Germline cysts: communes that work. PMID- 8453661 TI - RNA and protein elements of E. coli and lambda transcription antitermination complexes. PMID- 8453662 TI - Coding of olfactory information: topography of odorant receptor expression in the catfish olfactory epithelium. AB - Discrimination among the vast array of odors requires that the brain discern which of the numerous odorant receptors have been activated. If individual olfactory neurons express only a subset of the odorant receptor repertoire, then the nature of a given odorant can be discerned by identifying which cells have been activated. We performed in situ hybridization experiments demonstrating that individual olfactory neurons express different complements of odorant receptors and are therefore functionally distinct. Thus, a topographic map, defining either the positions of specific neurons in the epithelium or the positions of their projections, may be employed to determine the quality of an olfactory stimulus. Neurons expressing specific receptors appear to be randomly distributed within the olfactory epithelium. These data are consistent with a model in which randomly dispersed olfactory neurons with common receptor specificities project to common glomeruli in the olfactory bulb. PMID- 8453663 TI - kelch encodes a component of intercellular bridges in Drosophila egg chambers. AB - Oocyte maturation in Drosophila is supported by a cluster of 15 germline-derived nurse cells whose cytoplasm is transported into the oocyte through intercellular bridges called ring canals. kelch was isolated as a female sterile mutation affecting cytoplasm transport. We have cloned the kelch gene and found that it encodes an unusual transcript containing two open reading frames (ORF1 and ORF2) separated by a single UGA stop codon. At least two protein products are made from the kelch mRNA: a short protein from ORF1 and a longer protein from both ORF1 and ORF2 as a result of partial suppression of the UGA codon. The kelch ORF1 product is conserved, and antibodies directed against it are localized specifically to ring canals. Our results suggest that kelch produces a component of ring canals that regulates the flow of cytoplasm between cells. PMID- 8453664 TI - Immunoglobulin heavy and light chain genes rearrange independently at early stages of B cell development. AB - The compartment of mouse B cell progenitors can be resolved into five developmentally related fractions by multicolor flow cytometry. Using this system and employing mutant mice in which the membrane exon of the mu chain, the lambda 5 gene, or the JH locus was inactivated by gene targeting, we found that expression of the pre-B cell receptor complex is necessary for the transition from the large CD43+ to the small CD43- pre-B cell stage. We report the occurrence of immunoglobulin heavy and light chain gene rearrangement at the stage of large B cell precursors. We show that neither the pre-B cell receptor complex nor any gene rearrangement in the heavy chain locus is required for the induction of kappa light chain gene rearrangement in early B cell progenitors. PMID- 8453665 TI - The herbicide sensitivity gene CHL1 of Arabidopsis encodes a nitrate-inducible nitrate transporter. AB - This paper reports the identification and functional expression of a gene that is involved in nitrate uptake in plants, a process essential for the assimilation of nitrate and the biological removal of nitrate from the soil solution. The CHL1 gene of Arabidopsis, which when mutated confers resistance to the herbicide chlorate and a decrease in nitrate uptake, was isolated and found to encode a protein with 12 putative membrane-spanning segments. Injection of CHL1 mRNA into Xenopus oocytes produces a nitrate- and pH-dependent membrane depolarization, inward current, and nitrate uptake. These data show that the CHL1 gene encodes an electrogenic nitrate transporter. CHL1 mRNA is found predominantly in roots and displays nitrate- and pH-dependent regulation. PMID- 8453666 TI - CD8 is critically involved in lymphocyte activation by a T. brucei brucei released molecule. AB - T. brucei brucei released a lymphocyte triggering factor (TLTF), which triggered purified CD8+, but not CD4+, T cells to interferon gamma (IFN-gamma) mRNA expression and secretion and to [3H]thymidine incorporation. TLTF also induced mRNA for transforming growth factor beta, but not for interleukin-4. The action of this TLTF on mononuclear cell (MNC) cultures was blocked by anti-CD8 antibodies and by soluble CD8. MNCs from a mutant mouse strain lacking CD8 expression were not triggered by TLTF. IFN-gamma provides a growth stimulus for T. brucei brucei, and infected CD8- mice had much lower parasitemia and survived longer than CD8+ mice. The host-parasite interaction in experimental African trypanosomiasis thus involves parasite release of TLTF, which by binding to CD8 triggers CD8+ cells to produce the parasite growth-promoting cytokine IFN-gamma. PMID- 8453667 TI - The oncoprotein Bcl-3 directly transactivates through kappa B motifs via association with DNA-binding p50B homodimers. AB - Bcl-3 is an I kappa B-related protein with ankyrin repeat motifs. Its gene is located at a site of recurrent translocations in a subset of B cell chronic lymphocytic leukemias. Bcl-3 associates tightly with p50B (NFKB2, p52) homodimers in cells, and together these proteins form a ternary complex with DNA at kappa B sites. Such an association functionally leads to a novel and potent form of transactivation through the kappa B motif: the tethering of Bcl-3 to DNA via the p50B homodimers allows Bcl-3 to transactivate directly, while p50B homodimers alone cannot. Transactivation mediated by Bcl-3 requires two cooperating domains located amino- and carboxy-terminal to the ankyrin domain. Bcl-3 is localized to the nucleus, and a Bcl-3-p50B complex is detected in certain lymphoid cells. Our data reveal a novel role for Bcl-3, distinct from that of the inhibitor I kappa B. The results have implications for tumorigenesis. PMID- 8453668 TI - Binding affinities and cooperative interactions with bHLH activators delimit threshold responses to the dorsal gradient morphogen. AB - The dorsal (dl) morphogen gradient initiates the formation of the mesoderm, neuroectoderm, and dorsal ectoderm by setting different limits of regulatory gene expression along the dorsoventral axis of the early Drosophila embryo. In this paper, we show that low affinity dl-binding sites restrict target gene expression to the ventralmost regions (presumptive mesoderm), where there are peak levels of dl, while high affinity sites permit expression in ventrolateral regions (mesoderm and mesectoderm) containing intermediate levels of the morphogen. Activation by low levels of dl in lateral regions (the presumptive neuroectoderm) depends on cooperative DNA binding interactions between dl and bHLH proteins. The snail repressor blocks this interaction and restricts expression to the neuroectoderm. We discuss how enhancers serve as templates to bring weakly interacting regulatory factors into close proximity so that they can function combinatorially to activate and repress transcription. PMID- 8453669 TI - A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. AB - Neurofibromatosis 2 (NF2) is a dominantly inherited disorder characterized by the occurrence of bilateral vestibular schwannomas and other central nervous system tumors including multiple meningiomas. Genetic linkage studies and investigations of both sporadic and familial tumors suggest that NF2 is caused by inactivation of a tumor suppressor gene in chromosome 22q12. We have identified a candidate gene for the NF2 tumor suppressor that has suffered nonoverlapping deletions in DNA from two independent NF2 families and alterations in meningiomas from two unrelated NF2 patients. The candidate gene encodes a 587 amino acid protein with striking similarity to several members of a family of proteins proposed to link cytoskeletal components with proteins in the cell membrane. The NF2 gene may therefore constitute a novel class of tumor suppressor gene. PMID- 8453670 TI - ARIA, a protein that stimulates acetylcholine receptor synthesis, is a member of the neu ligand family. AB - Motor neurons stimulate their postsynaptic muscle targets to synthesize neurotransmitter receptors. Polypeptide signaling molecules may mediate this inductive interaction. Here we report the purification of ARIA, a protein that stimulates the synthesis of muscle acetylcholine receptors, and the isolation of ARIA cDNA. Recombinant ARIA increases acetylcholine receptor synthesis greater than 3-fold, and it induces tyrosine phosphorylation of a 185 kd muscle protein. The ARIA cDNA hybridizes with mRNAs that are expressed in the spinal cord from E4, a time prior to the onset of neuromuscular synapse formation, through adulthood. By E7, hybridizing mRNAs are concentrated in motor neurons. Chicken ARIA is homologous to the rat Neu differentiation factor and human here-gulin, ligands for the receptor tyrosine kinase encoded by the neu (c-erbB2, HER2) proto oncogene. Our data suggest that members of the ARIA protein family promote the formation and maintenance of chemical synapses and, furthermore, that receptor tyrosine kinases play important roles in this process. PMID- 8453671 TI - In vitro analysis of thymic microenvironmental effects on bone marrow cells of severe combined immunodeficient (SCID) mice. AB - The effect of the thymic microenvironment on thymocyte development from lymphohemopoietic cells was studied in an in vitro experimental model. Fetal thymus explants (FT, 15 days of gestation, C57BL/Ka, Thy1.1) were cocultured with bone marrow (BM) cells of severe combined immunodeficient (SCID, C.B.-17 scid/scid) or of normal BALB/c mice. The FT explants were depleted of their own lymphocytes either by irradiation (10 or 20 Gy) or by 2-deoxyguanosine (dGua) treatment. Development of SCID BM-derived Thy1+ cells was observed in coculture with the severely lymphocyte-depleted FT explants (dGua, 20 Gy), whereas BALB/c BM-type T cells were also apparent in the mildly irradiated (10 Gy) FT. The SCID BM-derived thymocytes were characterized as CD3- subpopulations expressing CD4/CD8 markers, while CD3+ CD4/CD8 subsets developed from the BALB/c mice. In contrast to results on BM-derived cells, cocultures of FT with thymus cells from SCID mice yielded CD3- CD4- CD8- Thy1.2+ cells, as opposed to BALB/c-derived Thy1.2+CD3+ cells exhibiting different CD4/CD8 phenotypes. Our data indicate that the BM cells from SCID mice can be induced to limited differentiation within the thymic microenvironment and this seems to be inhibited in the presence of resident radioresistant thymic cells. PMID- 8453672 TI - Polyclonal B-cell activation by an arthritogenic Staphylococcus aureus strain: contribution of T-cells and monokines. AB - We have recently described a murine model of Staphylococcus aureus-induced septic arthritis. One of the hallmarks of this disease is a striking hypergammaglobulinemia. In the present study we have used a sensitive ELISPOT technique to assess, at the single cell level, the B-cell differentiation properties of this arthritogenic, toxic shock syndrome toxin-1 (TSST-1)-producing staphylococcal strain. In vivo, inoculation of live S. aureus resulted in lymphoproliferation, early (within 3-4 days) peak of IgM-secreting cells and late (2 weeks after the injection) pronounced increase of IgG-secreting cells. We have documented that this late increase of IgG-secreting cells is a CD4+ T-cell dependent phenomenon. Furthermore, we have showed that there is a relationship between the hypergammaglobulinemia and the appearance of arthritis, since a nonarthritogenic staphylococcal strain will not give rise to increased frequency of immunoglobulin-secreting cells. To elucidate mechanisms responsible for S. aureus-induced polyclonal B-cell activation, we have assessed in vitro effects of formalin-fixed arthritogenic S. aureus on the release of cytokines. Our results show that the S. aureus LS-1 strain induces in vitro preferentially IgM-secreting cells, many of them displaying autoantibody properties. The magnitude of this response is high and comparable with optimal concentrations of LPS, a potent murine polyclonal B-cell activator. Interleukin-1 alpha (IL-1 alpha), tumor necrosis factor (TNF), and interleukin-6 (IL-6) were all secreted by mouse MNC after in vitro exposure to formalin-killed S. aureus. Inhibition experiments, using neutralizing antibodies to these cytokines, revealed that IL-1 alpha and IL 6 but not TNF-alpha had potent B-cell differentiation properties in S. aureus stimulated cell cultures. PMID- 8453673 TI - Signal transduction in cytotoxic lymphocytes: decreased calcium influx in NK cell inactivated with sensitive target cells. AB - Our laboratory has previously demonstrated that natural killer (NK) cell-mediated cytotoxicity is protein kinase C (PKC)-dependent and that PKC is translocated from the cytoplasm to the plasma membrane during NK cell activation. Furthermore, exposuring NK cells to a sensitive target cell for 4-6 hr at 37 degrees C rendered NK cells functionally inactive and these inactivated effector cells (i) do not turn over PI in response to K562 stimulation and (ii) lose mRNA for perforin and granzyme A and B less than 30 min after contact with K562. In this study, we first confirmed earlier findings that the interaction of sensitive target cells with human NK cells triggers an influx of extracellular calcium into NK cells. In addition, using flow cytometry we demonstrated that there was a delayed maximum uptake of extracellular calcium into functionally inactive NK cells when these cells were reexposed to fresh K562. Finally, we demonstrated that exposuring NK cells to K562 for 4 hr leads to a loss of NK cytotoxic activity and to the maximal expression of CD69. PMID- 8453675 TI - Do the CD45RO+CD8+ intestinal intraepithelial T lymphocytes have the characteristics of memory cells? AB - Human intraepithelial lymphocytes (IEL) are predominantly CD45RO+ (memory) CD8+ T lymphocytes located between intestinal epithelial cells. This study determines whether IEL share other characteristics with circulating CD45RO+ lymphocytes. Memory cells are large and have an upregulated expression of adhesion molecules. In contrast, the majority of IEL are the same size as peripheral blood (PB) T cells. In addition, IEL do not have an increased density of adhesion molecules, although a larger percentage express CD54 and CD58 compared to PBL. Allo-CTL activity, demonstrated by CD45RO+ PBL, could not be shown using either IEL or lamina propria lymphocytes (LPL) after a 5-day culture with alloantigen. However, after a 2.5-week culture with allogeneic PBL and interleukin-2 (IL-2), both IEL and LPL were capable of this cytotoxic function. The addition of IL-4 or IL-6 did not alter CTL activity by mucosal lymphocytes. Alloantigen-stimulated IEL, LPL, and PB CD8+ T cell lines were propagated for up to 16 weeks. All lines demonstrated alloantigen-specific proliferation. The PB CD8+ T lymphocytes maintained their phenotype and allo-CTL activity. In contrast, the CD4+ subset in the IEL and LPL became the predominant lymphocyte type and demonstrated potent lytic activity that was not alloantigen specific. This study shows that (1) IEL do not have increased density of adhesion molecules, (2) mucosal lymphocytes demonstrate allo-CTL activity, (3) CD8+ T cells in the mucosa cannot be perpetuated long-term by alloantigen and IL-2, and (4) mucosal CD4+ T cell lines demonstrate marked alloantigen-nonspecific cytotoxicity. The only characteristic shared by IEL and circulating memory cells is allo-CTL activity. PMID- 8453674 TI - In vivo activation of natural killer cells and priming of IL-2 responsive cytolytic cells by loxoribine (7-allyl-8-oxoguanosine). AB - Guanine ribonucleosides which have been substituted at the N7 and/or C8 positions have been shown previously to activate natural killer (NK) cells and to act as sparing agents for interleukin-2 (IL-2) in the in vitro generation of lymphokine activated killer (LAK) cells. In this paper we examined a disubstituted guanosine, 7-allyl-8-oxoguanosine (loxoribine), for the ability to activate NK cells and to interact with IL-2 in the generation of LAK cells in vivo. Following iv administration, loxoribine enhanced murine splenic NK activity in a dose related fashion, with optimal responses occurring at 3 mg/mouse. Enhanced lysis of YAC-1 cells was seen within 6 hr of injection and NK activity remained elevated for over 96 hr. Mature B and T cells were not required for NK activation since SCID mice responded to loxoribine within the same dose range as did the normal, immunocompetent mice. Both effector and precursor cells were eliminated by the administration of anti-asialo GM1 antibodies and NK activation was totally blocked in mice injected with anti-NK 1.1 antibodies. To test whether loxoribine would act as a sparing agent for IL-2 stimulated LAK activation, mice were injected with 2 mg loxoribine followed by twice daily administration of 10,000 units IL-2. In assays performed 48, 72, and 96 hr after injection of loxoribine, the cytolytic activity with the combination therapy exceeded the activity expected from the algebraic sum of the responses to the individual agents. Single injections of 2 mg loxoribine and 25,000 units IL-2 also stimulated NK/LAK activity, but the greatest enhancement was seen when loxoribine was administered 24 hr before the IL-2. Analysis of mRNA transcripts for the alpha chain of the IL 2 receptor indicated that gene transcription was enhanced within hours of loxoribine administration. PMID- 8453676 TI - Accelerated hematopoietic recovery and protective effect of the cyclooxygenase inhibitor indomethacin in bacterial infection of neutropenic mice. AB - The effects of indomethacin administration on Pseudomonas aeruginosa infection were investigated in neutropenic mice. Cyclophosphamide-treated mice received the drug at 2.5 to 12 mg/kg according to different regimens, to be challenged with a lethal intraperitoneal inoculum of P. aeruginosa 5 days after myelosuppression. A single exposure of the neutropenic mice to 7 mg/kg indomethacin during the first 6 to 48 hr after myelosuppression was found to optimally restore the animals' antibacterial resistance, both in terms of survival of infected mice and clearance of the organisms from the peritoneal cavity. However, when administered 24 hr before challenge, the same drug dosage had no effect in enhancing survival. Cure was associated with accelerated hematopoietic recovery, as revealed by peripheral blood leukocyte counts, spleen weight and cellularity, cellular response to infection in the peritoneal cavity, and enumeration in vitro of bone marrow and splenic granulocyte-macrophage colony-forming cells. Following indomethacin administration, a rapid burst in the levels of colony-stimulating activity was detected in the bloodstream, and exposure of splenic macrophages or marrow cells to indomethacin in vitro was found to result in enhanced expression of transcripts specific for granulocyte-macrophage colony-stimulating factor. These data support the notion that the administration of cyclooxygenase inhibitors may be useful in promoting hematopoiesis and reducing the risk of opportunistic infections in myelosuppressed hosts. PMID- 8453677 TI - Molecular events in B lymphocyte activation: consequences of signals transduced through MHC class II molecules. AB - Evidence is presented to demonstrate that murine B lymphocytes receive growth stimulatory signals from their surface class II molecules. Monoclonal anti-Ia antibodies enhanced anti-mu-induced B cell proliferative response. The signals through surface immunoglobulin (Ig) and Ia appeared to act sequentially since preexposure to anti-mu was required to observe anti-Ia-induced increase in B cell proliferation. Anti-Ia antibodies did not increase the number of B cells entering the G1 phase of cell cycle but always enhanced transition from G1 into the S phase in response to stimulation with anti-mu. Analysis of early gene expression revealed that signaling through class II molecules led to an increase in anti-mu induced expression of c-myc, a proto-oncogene, and of ornithine decarboxylase, a key enzyme in polyamine biosynthesis that has been shown to be intimately related to increased cell proliferation. PMID- 8453678 TI - Thrombin enhances T cell proliferative responses and cytokine production. AB - Human alpha-thrombin, in addition to its procoagulant activity, is a mitogen for fibroblasts and endothelial cells and a chemotactic agent for monocytes. To further understand the complex physiological functions of thrombin, we investigated whether thrombin has any immunoregulatory function with regard to T cell activation. Using highly purified human alpha-thrombin and peripheral blood mononuclear cells (PBMC), we investigated whether thrombin has any effect on cytokine production and/or proliferation induced by different T cell stimuli. At physiological concentrations (1-10 micrograms/ml, 30-300 nM), thrombin significantly enhances T cell proliferation in response to mitogens, superantigens, alloantigens, and anti-CD3 stimulation. Enhanced proliferation was associated with increased IL2 and IL6 production and with an increase in the number of IL2r+ (CD25)-bearing T cells. Thrombin alone was not mitogenic nor did it induce IL2 production or increase the number of IL2r+ T cells. However, PBMC exposed to thrombin alone produced high levels of IL6. Thrombin also enhanced IL2 induced proliferation of murine and human IL2-dependent cell lines. These results suggest that thrombin may play an important role in regulating cell-mediated immunity. PMID- 8453679 TI - Regulation of human natural cytotoxicity by IgG. IV. Association between binding of monomeric IgG to the Fc receptors on large granular lymphocytes and inhibition of natural killer (NK) cell activity. AB - The regulation of human natural killer (NK) activity by IgG described previously by us depends on the ability of cytophilic molecules of monomeric IgG (mIgG) to inhibit the subsequent killing of NK-sensitive targets. Highly purified NK cells obtained from human peripheral blood are able to directly bind mIgG as well as antigen-complexed IgG through its Fc region. The demonstration that NK cells bear labile cytophilic IgG, a property which usually has been attributed to L cells, indicates that mIgG-induced inhibition of NK activity is mediated by direct interactions between the inhibitory ligand and cytotoxic effector cells. The Fc receptor (FcR) mediating downregulation of NK cytotoxicity appeared to be FcR gamma III, previously found to be selectively expressed on NK cells and granulocytes. In studies of unidirectional cross-inhibition of mIgG binding to NK cells by various anti-CD16 monoclonal antibodies, binding characteristics of mIgG or complexed IgG were similar. Thus, the FcR gamma III for mIgG appear to be indistinguishable from receptors responsible for binding of polymeric IgG on human NK cells. The negative regulation of NK activity by mIgG was not attributable to inhibition of conjugate formation between effector cells and K532 targets, but rather to inhibition of a post-binding event involved in killing of conjugated targets. The data presented suggest that the Fc gamma RIII on human NK cells can either mediate killing against IgG antibody-coated target cells or, upon interaction with cytophilic monomeric ligand in soluble form, induce inhibition of NK activity. PMID- 8453680 TI - Low versus high density of immobilized anti-CD3 influences IL-4 regulation of T cell immune responses. AB - Varying the concentration of anti-CD3 immobilized on Sepharose beads allowed us to study both the inhibitory and the stimulatory effects of IL-4 on purified T cells and contrast IL-4 versus IL-2-driven T-cell proliferative responses. In the presence of low density immobilized anti-CD3, IL-4 was unable to stimulate purified T cells and was inhibitory to IL-2-driven T-cell responses. The inhibitory effects of IL-4 were enhanced by preincubation of T cells with IL-4 prior to stimulation. In contrast, the inhibitory effects of IL-4 could be avoided by delaying the addition of IL-4 until Days 3-5 of culture or they could be reversed by the addition of IL-1. In the presence of high-density anti-CD3, IL 4 elicited an IL-2-independent proliferative response by purified T cells or sorted CD8+ cells. Comparison of IL-4-driven versus IL-2-driven T-cell responses demonstrated that IL-2 was able to upregulate mRNA for IL-4 receptors and interferon-gamma, while IL-4 had minimal effects on upregulating mRNA for either the p55 or the p75 IL-2 receptor subunits or interferon-gamma. The timing of the presence of IL-4, the state of T-cell activation, and the nature and strength of the stimulatory signal influenced the regulatory effect of IL-4 on the immune response. PMID- 8453681 TI - Prochlorperazine as a doxorubicin-efflux blocker: phase I clinical and pharmacokinetics studies. AB - Doxorubicin (DOX) efflux in drug-resistant cells is blocked by phenothiazines such as trifluoperazine (TFP) and prochlorperazine (PCZ) in vitro. The present phase I study was conducted in 13 patients with advanced, incurable, nonhematologic tumors to determine whether PCZ plasma levels high enough to block DOX efflux could be achieved in vivo. The treatment schedule consisted of prehydration and i.v. administration of 15, 30, 50, and 75 mg/m2 PCZ followed by a standard dose of 60 mg/m2 DOX. The hematologic toxicities attributable to DOX were as expected and independent of the PCZ dose used. Toxicities attributable to PCZ were sedation, dryness of the mouth, cramps, chills, and restlessness. The maximal tolerated dose (MTD) of PCZ in this schedule was 75 mg/m2. Pharmacokinetic analysis indicated a large interpatient variation in peak plasma PCZ levels that ranged from 95 to 1100 ng/ml. The three plasma half-lives of PCZ were: t1/2 alpha (+/- SE), 20.9 +/- 5.3 min; t1/2 beta, 1.8 +/- 0.3 h; and t1/2 gamma, 21.9 +/- 5.3 h. The volume of distribution (Vd), total clearance (ClT), and area under the curve (AUC) for PCZ were 2254 +/- 886 l/m2, 60.2 +/- 13.5 l m 2 h-1, and 1624 +/- 686 ng ml-1 h, respectively. DOX retention in tumor cells retrieved from patients during the course of therapy indicated the appearance of cells with enhanced DOX retention. The combination of DOX and high-dose i.v. PCZ appeared to be safe, well tolerated, and active in non-small-cell lung carcinoma. PMID- 8453682 TI - Dose-ranging evaluation of the substituted benzamide dazopride when used as an antiemetic in patients receiving anticancer chemotherapy. AB - Dazopride, a substituted benzamide structurally related to metoclopramide, is a potent gastric prokinetic agent that prevents cisplatin-induced emesis in animals. Unlike metoclopramide, dazopride has no effect on dopamine receptors and therefore should not produce extrapyramidal side effects. In this dose-ranging trial, 23 patients with cancer receiving chemotherapy known to produce nausea and vomiting received three i.v. infusions of dazopride every 2 h beginning 30 min before the chemotherapy. Seven dose levels were explored ranging from 0.5 to 4.0 mg/kg in each of the three infusions. Toxicities were mild and included sedation, dizziness, visual disturbances, and headaches. All side effects were transient and were not dose-related. Antiemetic effects were observed. Dazopride can be safely given on this schedule at doses of up to 4.0 mg/kg to patients receiving chemotherapy. On the basis of the results of this trial, further studies of this agent are warranted. PMID- 8453683 TI - Direct delivery of platinum-based antineoplastics to the central nervous system: a toxicity and ultrastructural study. AB - Platinum drugs are playing an increasingly major role in cancer treatment, but systemic administration of these agents has resulted in significant toxicity. To examine the effects of cisplatin and two newer agents, iproplatin and carboplatin, we injected the agents directly into the cerebrospinal fluid of rats and found that neurotoxic reactions resulted from doses of cisplatin (10 nmol) much lower than those of iproplatin (40 nmol) or carboplatin (80 nmol). Moreover, central nervous system tissue appeared to be less adversely affected by direct exposure to carboplatin since chronic toxicity was not observed in any of the animals receiving carboplatin until a lethal dose was reached. Furthermore, only the animals receiving cisplatin showed histologic damage in their spinal cords, and ultrastructural studies confirmed that while significant abnormalities were observed in the spinal cords of rats receiving 40 nmol cisplatin, no architectural changes were detected in the spinal cords of animals receiving 240 nmol carboplatin. We conclude that platinum drugs can be delivered intrathecally to achieve a much greater concentration of active drug than can be achieved by intravenous administration and that carboplatin appears to be the most suitable platinum-based drug for use in systems delivering drugs directly to the brain and spinal cord. PMID- 8453684 TI - Effect of hyperthermia on the activity of 1-[(4'-hydroxy-2'-butenoxy)methyl]-2 nitroimidazole, which is cytotoxic to hypoxic cells. AB - The effect on EMT6/KU cells of a newly synthesized hypoxic cell sensitizer, 1 [(4'-hydroxy-2'-butenoxy)methyl]-2-nitroimidazole (RK28), combined with heat was determined in vitro under conditions of hypoxia. As compared with aerobic conditions, hypoxia produced a 1.30-fold increase in the cytotoxicity of the drug for mouse mammary EMT6/KU cells induced by 1 h heat treatment at 43 degrees C in medium with a normal pH. Hypoxia also reduced the surviving fraction of cells treated with both RK28 alone for 2 h and the same concentrations of RK28 and heat (43 degrees C) in combination. Those enhancement ratios corresponded to a 20.3- and > 345-fold increase, respectively. Moreover, concomitant treatment with RK28 and heat greatly inhibited the clonogenic activity of the EMT6/KU cells under conditions of in vitro hypoxia and in all experimental groups; there was a statistically significant difference in the time-response curves (P < 0.05). As hypoxic cells in a solid tumor are resistant to various anticancer drugs, RK28 combined with hyperthermia deserves further study for possible clinical applications. PMID- 8453685 TI - Comparison of the adrenalytic activity of mitotane and a methylated homolog on normal adrenal cortex and adrenal cortical carcinoma. AB - Mitotane is an important adrenalytic drug for the treatment of adrenal cancer whose use is limited by toxicity. Reports from another laboratory indicated that a methylated homolog of Mitotane (Mitometh) tested in guinea pigs possessed comparable adrenalytic activity but was less toxic than Mitotane. This observation prompted us to undertake a comparative study of these two drugs on the basis that Mitometh may be a superior agent for the treatment of adrenal cancer. Preliminary studies in guinea pigs failed to show a significant adrenalytic effect for either Mitotane or Mitometh. Thus, we extended the study to 13 mongrel dogs weighing 12-15 kg that were treated daily with Mitometh or Mitotane (50-100 mg/kg) for 6 or 12 days. Cortisol decreased to undetectable levels and adrenocorticotropic hormone (ACTH) rose to 10 times the baseline levels within 72 h in Mitotane-treated animals. Despite the achievement of similar drug levels, Mitometh treatment in dogs failed to suppress cortisol or increase ACTH. To determine whether these differences were due to differences in bioavailability, we measured the relative concentration of Mitotane and Mitometh in homogenates of adrenal cortex obtained from Mitotane- and Mitometh-treated dogs. The adrenal concentration of Mitometh determined in Mitometh-treated dogs was 5 times higher than the concentration of Mitotane measured in Mitotane treated animals. Whereas the adrenal glands of Mitotane-treated dogs showed hemorrhage and necrosis, the Mitometh-treated animals showed no adrenal damage. Despite the lack of adrenalytic activity, Mitometh maintained its toxicity as demonstrated by microscopic evidence of hepatic necrosis and an increase in hepatic enzymes. The adrenalytic effects of both agents was also studied in vitro using a human functioning adrenal cortical carcinoma cell line, NCI-H295. Whereas Mitotane strongly suppressed cell growth, Mitometh had a weaker effect. We conclude that Mitometh is not likely to be effective in the therapy of adrenal cancer. Moreover, the results of this study are supportive of the view that metabolic transformation of Mitotane is in some way linked to its adrenalytic action. PMID- 8453686 TI - Biodistribution and toxicity of photoproducts of merocyanine 540. AB - Light-activated merocyanine 540 (pMC540) has been shown in our earlier studies to be effective against certain types of tumor cells and viruses, including human immunodeficiency virus (HIV-1). To test the potential extracorporeal and systemic use of pMC540, its toxicity was investigated in DBA/2 mice, pigs, and dogs. The lethal dose in DBA/2 mice after an i.p. injection was 370 mg/kg, and the 50% lethal dose (LD50) was 320 mg/kg; however, following i.v. administration, the lethal dose and the LD50 dose were 240 and 160 mg/kg, respectively. Tritium labeled MC540 was used to study the biodistribution of pMC540 in DBA/2 mice. Almost 70% of the injected radioactivity was excreted within 6 h of injection. After 1 week, the pMC540 was almost completely cleared, with only 1.89% of the activity remaining, and had a plasma half-life of 23 h. Pigs injected with an accumulated dose of 10 mg/kg and followed for a period of 30 days did not show adverse signs of toxicity as monitored by SMAC-28 analysis, CBC profile, and blood-coagulation studies. A dog injected with a single dose of 20 mg/kg showed induction of the hepatic enzymes glutamic oxaloacetic transaminase (AST) and glutamic pyruvic transaminase (AST); however, serum levels of gamma-glutamyl transpeptidase (GGT) remained unchanged. The data presented herein may serve to identify certain drug-dose limitations in the systemic use of pMC540. PMID- 8453687 TI - Pharmacokinetics of (1R,2R-diaminocyclohexane)oxalatoplatinum(II) in comparison with cisplatin following a single intravenous injection in rabbits. AB - The pharmacokinetics of (1R,2R-diaminocyclohexane)oxalatoplatinum(II) (1-OHP, NSC 266046), a second-generation antitumor platinum complex, was studied in rabbits and compared with that of cisplatin. The rabbits were given a single i.v. dose of 1-OHP or cisplatin (10 mumol/kg). A comparison of tissue platinum levels at 24 h postinjection showed that platinum levels were lower in the eight organs examined, which included the kidney and liver, after the injection of 1-OHP than following cisplatin administration. Plasma-decay profiles of three platinum species, that is, the unchanged species, filterable platinum, and total platinum, were examined. Plasma levels of the unchanged species and filterable platinum for 1-OHP declined more rapidly than those for cisplatin. The ratio of plasma filterable-to-total platinum indicated that the protein-binding ability of 1-OHP was greater than that of cisplatin. As for urinary excretion, amounts of the unchanged species and total platinum excreted during the 24 h period postinjection were 28% and 76% of the dose for 1-OHP and 23% and 57% of the dose for cisplatin, respectively. The renal clearance of both the unchanged species and filterable platinum in plasma for 1-OHP was about 2-fold that for cisplatin. 1-OHP is reported to be much less nephrotoxic than cisplatin. This may be due in part to its pharmacokinetic behavior or to pharmacokinetic differences resulting from chemical reactions that make 1-OHP less toxic than cisplatin. PMID- 8453688 TI - Therapy of refractory/relapsed acute myeloid leukemia and blast crisis of chronic myeloid leukemia with the combination of cytosine arabinoside, tetrahydrouridine, and carboplatin. AB - Eight patients, of whom four had acute myeloid leukemia (AML) and four had chronic myeloid leukemia (CML) blast crisis, were treated with a combination of cytosine arabinoside (ARA-C: 1,600 mg/m2 in three patients, 1,200 mg/m2 in five patients), tetrahydrouridine (THU: 2,800 mg/m2 in two patients, 2,646 mg/m2 in one patient, 2,100 mg/m2 in five patients), and carboplatin (900 mg/m2 in four patients, 720 mg/m2 in one patient, 450 mg/m2 in three patients). As a result of this treatment, five of the eight patients became aplastic. Two of the four patients with CML blast crisis reverted to the chronic phase and two of the four patients with acute nonlymphocytic leukemia (ANLL) attained a remission (one partial remission and one complete remission). The major toxicities included myelosuppression, unacceptable hepatotoxicity, and diarrhea. Pharmacokinetics studies revealed that the addition of carboplatin did not significantly change the disposition of ARA-C. ARA-C levels were not significantly changed in comparison with those obtained in a prior study of ARA-C with THU (ARA-C plasma levels at 3 h, 2630 +/- 1170 ng/ml). PMID- 8453689 TI - An in vivo and in vitro trial of aclarubicin in metastatic breast cancer: a novel approach to the study of analogs. AB - Aclarubicin is an anthracycline antibiotic that differs from doxorubicin in its structure, mechanism of action, and preclinical toxicity profile, especially its reduced cardiotoxicity. We therefore conducted a side-by-side in vivo and in vitro trial of this agent in metastatic breast-cancer patients and their biopsied tumor specimens, respectively. Aclarubicin (100 mg/m2) was given by intravenous infusion every 3 weeks to 22 patients with objectively measurable metastatic breast cancer, 15 of whom had not previously received doxorubicin. The dose limiting toxicity consisted primarily of leukopenia and severe nausea and vomiting. No objective response was observed in the 19 evaluable patients. After disease progression, 10 of the 15 doxorubicin-naive patients were treated with doxorubicin; 6 patients achieved a partial response, including 4 who responded to doxorubicin alone and 2 who responded to doxorubicin in combination with thiotepa and vinblastine. Tumor specimens were obtained from 14 of the 22 patients prior to the start of therapy and were tested for in vitro sensitivity to aclarubicin and doxorubicin using a soft agar colony-forming assay. Adequate colony growth occurred in 9 of 14 cultured tumor specimens. All 9 specimens, including 3 obtained from doxorubicin-naive patients, demonstrated in vitro resistance to aclarubicin. In all, 1 of 3 specimens taken from doxorubicin-naive patients demonstrated in vitro sensitivity to doxorubicin, whereas 6 tumor specimens obtained from patients who had undergone prior doxorubicin therapy demonstrated in vitro resistance. The patient whose tumor demonstrated in vitro doxorubicin sensitivity responded to a doxorubicin regimen after failing aclarubicin treatment; in vitro doxorubicin resistance correlated with clinical resistance in all cases. We conclude that aclarubicin is inactive in metastatic breast cancer at the dose and schedule used. Side-by-side in vivo and in vitro trials are feasible and could be useful in the development of investigational agents with activity greater than that of aclarubicin and, particularly, in the evaluation of analogs of clinically active drugs. PMID- 8453690 TI - Combination of daily 4-h infusion of 5-fluorouracil and cisplatin in the treatment of advanced head and neck squamous-cell carcinoma: a South-East European Oncology Group study. AB - Between April 1986 and May 1989 a multicentre study was conducted to evaluate the efficacy of a 4-h intravenous infusion of 1000 mg/m2 5-fluorouracil (5-FU) followed by a 1-h infusion of 25 mg/m2 cisplatin (CDDP) given for 4 consecutive days every 4 weeks to patients with advanced squamous-cell carcinoma of the head and neck. A total of 189 consecutive patients entered the study, including 106 who had previously undergone chemotherapy and 83 who were chemotherapy-naive. Of the 165 evaluable patients, 96 (58%) responded to treatment, including 22 (13%) who achieved a complete remission (CR). In the group of previously untreated patients an objective response (CR+PR) was seen in 78% (CR, 14%) whereas in pretreated patients the response rate (CR+PR) was 40% (CR, 13%). The median survival period was 10 months. No significant difference in the duration of survival or of remission was found between the two groups in relation to previous therapy, tumour localisation, disease stage or performance status. Almost half of the patients (49%) experienced leucopenia but it was severe in only 11% of cases. Anemia (mainly WHO grades 1-2) occurred in 38% of the patients. Nausea and vomiting were common (84%). Nephrotoxicity (23%) was mild and of short duration. Moderate hair loss was seen in 42% of the patients, and phlebitis occurred in 8%. A few cases of cardiotoxicity and neurotoxicity were observed. This regimen is well tolerated and can be given even on an outpatient basis. The resultant response rate and side effects appear to be similar to those previously reported for combination chemotherapy with CDDP and continuous 5-FU infusion. PMID- 8453691 TI - Evidence of an absorption phase after short intravenous suramin infusions. AB - Suramin was given as an intravenous infusion to 16 cancer patients in a phase I trial. Individual pharmacokinetic parameters were calculated from a test dose given 1 week prior to the administration of a full-dose (350-700 mg/m2) regimen of 1-h loading and maintenance infusions. A distribution phase of 3.8 h was found. Plasma suramin concentrations were noted to increase following cessation of the intravenous test infusion in eight subjects. A model is proposed in which high-capacity, low-affinity binding of suramin to a shallow compartment adjacent to the intravascular space occurs rapidly during infusion, followed by absorption back into the measured blood pool with binding to plasma albumin. Despite the observable presence of this postinfusion peak shortly after the cessation of the brief suramin infusion, the pharmacokinetics of suramin were best characterized by a traditional two-compartment model. The dose-adjusted area under the concentration-time curve (AUC) increased with dose, supporting a hypothesis of sustained absorption of suramin to vascular endothelium but also raising the possibility of dose-dependent clearance. PMID- 8453692 TI - Drug- and radiation-induced resistance in a human neurogenic sarcoma xenografted in nude mice. AB - The in vivo development of radiation- and doxorubicin-induced resistance was studied in a chemosensitive and radiosensitive human neurogenic sarcoma (Essen neuroectodermal tumor line 2) xenografted in nude mice. Dose-response curves were generated for the parent tumor line, and growth delay (GD) and specific growth delay (SGD) were the study end points. An intravenous injection of doxorubicin at 10 mg/kg, the lethal dose for 10% of the study population (LD10) in nude mice, and a single dose of 12 Gy radiation were determined to be isoeffective and were thus maintained for all subsequent treatments. For the induction of resistance to both treatment modalities, regrowing tumors were transplanted into successive generations of nude mice and retreated. This procedure was repeated 13 and 9 times, respectively, for the doxorubicin and radiation treatments. The response was monitored in all passages. As compared with the parent tumor line, a 50% decrease in SGD was observed following 3.9 and 8.5 treatments with doxorubicin and radiation, respectively. Following four treatments with doxorubicin, SGD in tumors crossed over to radiation therapy declined by 50%. Radiation therapy, on the other hand, caused significant reductions in GD and SGD in tumors that were subsequently exposed to doxorubicin, but it did not induce a 50% decline in response. Overexpression of P-170-glycoprotein was not observed for either treatment modality. The data suggest that treatment with doxorubicin or radiation can potentially induce resistance to subsequent continued or crossover treatment and that this resistance develops gradually. The lack of P-170-glycoprotein over expression in the resistant cell lines indicates the existence of alternative pathways that may lead to resistance. PMID- 8453693 TI - Single-agent ifosfamide studies in sarcomas of soft tissue and bone: the M.D. Anderson experience. AB - We have used ifosfamide to treat patients with sarcomas in four completed single agent protocols and one pilot study since 1985. All the studies have used either N-acetyl-L-cysteine (NAC) or mesna as a uroprotective agent, except in one arm of one study where hydration alone was employed. Mesna has proven superior to NAC in providing protection against ifosfamide-induced hematuria. Mesna given as a loading dose followed by continuous 24-h infusion has been effective and most practical in this regard. Ifosfamide has demonstrated clinically useful antitumor activity in our hands against most sarcoma subtypes. Our studies suggest a dose response relationship for ifosfamide. At a total dose of 6 g/m2 per course, the overall response rate was 10%; at 10 g/m2 per course, it rose to 21%. Future clinical trials will determine ifosfamide's role in combination chemotherapy and more clearly define the best schedule or schedules for the uroprotective administration of mesna. PMID- 8453694 TI - Cyclophosphamide versus ifosfamide: a randomized phase II trial in adult soft tissue sarcomas. The European Organization for Research and Treatment of Cancer [EORTC], Soft Tissue and Bone Sarcoma Group. AB - Ifosfamide (5 g/m2) was compared with its parent analogue cyclophosphamide (1.5 g/m2) in a randomized phase II study. Both drugs were given by 24-h intravenous (i.v.) infusion every 3 weeks along with i.v. bolus infusions of mesna (400 mg/m2), which was given every 4 h for nine administrations. Eligibility criteria included an age of 15-75 years, biopsy-proven advanced metastatic soft-tissue sarcoma, and a World Health Organization performance status of 0-2. Exclusion criteria were prior treatment with classic alkylating agents, a creatinine level of > 150 mumol/l, a bilirubin level of > 20 mumol/l, a leukocyte cell count of < 3.5 x 10(9)/l, and a platelet count of < 100 x 10(9)/l. A total of 171 patients were entered, 24 of whom were ineligible and 12, inevaluable, leaving 135 patients evaluable. In all, 67 patients were treated with cyclophosphamide, and the overall response rate was 7.5%. All responders to cyclophosphamide were patients who had not received prior chemotherapy (13% of 38 patients). Another 68 patients were given ifosfamide, 18% of whom responded to treatment. Of the 28 ifosfamide-treated patients who had received prior chemotherapy, 7% were responders. The response rate for the remaining 40 patients was 25%. The higher overall response rate (P = 0.13) obtained with less myelosuppression in ifosfamide-treated patients suggests that this agent may have advantages over cyclophosphamide in combination therapy. PMID- 8453695 TI - Ifosfamide combination regimens for soft-tissue sarcoma. AB - Two trials using ifosfamide-based combination chemotherapy for advanced soft tissue sarcoma have been completed. In the first study, 50 evaluable patients received ifosfamide (5 g/m2) with mesna (5 g/m2) and doxorubicin (40 or 60 mg/m2) intravenously (i.v.) every 3 weeks. In all, 11 patients (22%) achieved an objective response [3 complete responses (CRs) and 8 partial responses (PRs)]. Toxicities included leukopenia, febrile neutropenia, nausea and vomiting, and alopecia. The overall median survival was 12 months. In the second study, 51 evaluable patients received ifosfamide (3 g/m2) with mesna (3 g/m2), both being given i.v. on day 1, together with etoposide (100 mg/m2) infused i.v. daily for 3 days. Six patients (12%) achieved objective responses (1 CR, 5 PRs). Toxicities included leukopenia, nausea and vomiting, and alopecia. The overall median survival was 7.4 months. Neither of these combination regimens appears to be more effective in advanced soft-tissue sarcoma than single-agent therapy with either ifosfamide or doxorubicin. If the results of chemotherapy in the management of these tumors are to be improved a new approach to therapy is clearly required. PMID- 8453696 TI - Treatment results obtained in metastatic soft-tissue sarcoma with a combination of doxorubicin and dacarbazine or doxorubicin and ifosfamide. AB - Between 1982 and 1986, 38 patients with soft-tissue sarcomas were treated with the combination doxorubicin/dacarbazine (group A); between 1986 and 1990, another 46 patients received doxorubicin/ifosfamide (group B); and between 1990 and 1991, 11 patients received an alternating regimen of doxorubicin and ifosfamide (group C). The patients' characteristics were comparable among the three groups. Overall remission rates were 34% in group A, 44% in group B, and 18% in group C. The duration of remission was 10 months and the median survival was 13 months in groups A and B. Toxicity, especially myelotoxicity, was severe, with no marked differences being noted between the groups. We conclude that both doxorubicin/dacarbazine and doxorubicin/ifosfamide are active regimens in metastatic soft-tissue sarcomas; nevertheless, the overall prognosis for these patients remains poor. PMID- 8453697 TI - Ifosfamide in the treatment of soft-tissue sarcomas: experience at the West German Tumor Center, Essen. AB - The response of ifosfamide-based chemotherapeutic regimens was retrospectively analyzed in adult patients with advanced soft-tissue sarcoma who were treated at the West German Tumor Center, Essen, between 1978 and 1990. Single-agent ifosfamide was given either in split doses of 60-80 mg/kg by 4-h infusion over 5 days or as a continuous 24-h infusion of 5 g/m2. Ifosfamide was given either in split doses of 40-50 mg/kg over 5 days or as a continuous infusion of 5 g/m2 in combination with doxorubicin (40-60 mg/m2, day 1), cisplatin (20 mg/m2, days 1 5), or etoposide (100 mg/m2, days 1, 3, and 5). Mesna was given to all patients as prophylaxis against urotoxicity. Of 54 evaluable patients receiving single agent ifosfamide, 5 achieved a complete response (CR) and 10 showed a partial response (PR), for an overall response rate of 28%. Objective responses were more frequent in previously untreated patients (47%) than in pretreated patients (15%; P < 0.01). The addition of doxorubicin (n = 41) or cisplatin (n = 29) to ifosfamide did not significantly increase the response rate (29% and 41%, respectively) or median duration of remission as compared with ifosfamide alone. In addition, no significant difference was observed between the two ifosfamide regimens used: the 24-h continuous-infusion schedule (5 g/m2 per course, 27% response rate) and the 5-day fractionated regimen (10-15 g/m2 per course, 19% response rate). We conclude that the response and the median duration of remission produced by single-agent ifosfamide compare favorably with the results achieved using single-agent doxorubicin and the usually more toxic combination regimens. PMID- 8453698 TI - Feasibility study of postoperative adjuvant chemotherapy and radiotherapy for soft-tissue sarcoma. AB - In a nonrandomized trial, postoperative, adjuvant, combined chemotherapy and radiotherapy were given to 17 patients with high-grade soft-tissue sarcomas. All patients had undergone conservative limb-sparing surgery. Soft-tissue sarcomas were localized in the extremities (13 patients), superficial trunk (3), and neck (1). In all, 13 patients received 50 mg/m2 doxorubicin and 5 g/m2 ifosfamide with mesna uroprotection for a total of 6 cycles and 4 patients received CYVADIC (cyclophosphamide/vincristine/doxorubicin/dacarbazine). Chemotherapy was started immediately after wound healing. Irradiation using the shrinking-field technique was commenced 3-7 days following chemotherapy; a total dose of 65 Gy was applied. The major side effects of chemotherapy were nausea and vomiting [17 of 17 patients, 5 experiencing World Health Organization (WHO) grade 3 toxicity and 1, WHO grade 4], leukopenia of <3.0 x 10(9)/l (17 patients), and leukopenia of <1.0 x 10(9)/l (7 patients). The median leukocyte nadir was reached on day 11 (range, days 7-16). The duration of critical leukopenia did not exceed 1 week. Reversible alopecia occurred in all patients. Temporary cardiomyopathy was recorded in 1 patient. Following radiotherapy, 11 episodes of epitheliolysis and 1 case of moderate lymphedema were documented. There was no life-threatening condition. After a follow-up of 58 months, the outcome was as follows: disease-free survival, 9 patients; distant metastases, 7; local recurrence, 1. Excluding 3 patients who entered the study after undergoing surgery for local relapse, the rate of distant metastases was 36%. In summary, the postoperative use of chemotherapy/radiotherapy is feasible, producing relevant but manageable toxicity. This combination results in effective local tumor control with good functional results following limb-sparing surgery. The incidence of distant metastases, however, is high. PMID- 8453699 TI - Ifosfamide plus doxorubicin in previously untreated patients with advanced soft tissue sarcoma. AB - The objective of this phase II trial was to assess the therapeutic activity and toxicity of doxorubicin plus ifosfamide in previously untreated patients with advanced soft-tissue sarcoma. Treatment consisted of an intravenous bolus injection of doxorubicin at a dose of 50 mg/m2 followed by a 24-h infusion of ifosfamide at 5 g/m2 plus mesna, with therapy being repeated every 3 weeks until disease progression or unacceptable toxicity occurred. Of the 203 patients entered, 175 were evaluable for response. The overall response rate was 35% (95% confidence interval, 28%-42%), with 9% of patients achieving complete responses and 26% showing partial responses. The median time to progression was 29 weeks for all evaluable patients and 67, 40, and 28 weeks for complete and partial responders and patients with stable disease, respectively. The median duration of survival was 58 weeks. Myelosuppression was the dose-limiting toxicity, resulting in leukopenia (World Health Organization grades 3 and 4) in 73% of the evaluable patients. Other side effects were rare and usually well manageable. PMID- 8453700 TI - Preoperative doxorubicin plus ifosfamide in primary soft-tissue sarcomas of the extremities. AB - A total of 51 patients with large, primary, high-grade soft-tissue sarcomas of the extremities were treated at our institute with two preoperative and three postoperative cycles of doxorubicin plus ifosfamide/mesna. Preoperative doxorubicin was given intra-arterially for lesions of the lower extremities. Of 47 evaluable patients, 22 (47%) showed clinical responses and 21 (45%), pathologic responses. Clinical and pathologic responses, however, were not necessarily coincident in the same patient. Conservative limb-sparing surgery was performed in 41 cases (87%), and in 4 cases amputation was avoided as a result of the local improvement induced by chemotherapy. Local recurrence occurred in 12 cases (25%), 3 of which required further amputation. Although the follow-up period was only 28 months, the 4-year actuarial survival was 91% and the 4-year metastasis-free value was 69%. An evident difference existed between patients who showed a documented clinical response to chemotherapy and those who did not, the 4-year metastasis-free value being 85% and 59% (P = 0.1), respectively. Adjuvant preoperative chemotherapy may allow for limb-salvage surgical procedures in selected cases. PMID- 8453701 TI - Phase II trial of ifosfamide and cisplatin in the treatment of metastatic sarcomas: a Southwest Oncology Group study. AB - The Southwest Oncology Group (SWOG) performed a phase II trial of a combination of ifosfamide/mesna/cisplatin in patients with metastatic soft-tissue sarcoma who had previously received one chemotherapeutic regimen. A total of 39 patients were registered in the study, including 7 treated during a limited-institution pilot phase; 38 patients were fully eligible and evaluable. During the pilot phase, patients were treated with 2.5 g/m2 ifosfamide daily on days 1-3, 2.5 g/m2 mesna daily on days 1-4, and 100 mg/m2 cisplatin on days 2 and 9. Due to excessive myelosuppression, the day-9 cisplatin dose was dropped when the study was opened groupwide, and the subsequent 32 patients were treated at 3- to 4-week intervals with 2.5 g/m2 ifosfamide daily on days 1-3, 2.5 g/m2 mesna daily on days 1-4, and 100 mg/m2 cisplatin on day 2. Myelosuppression was severe, with granulocytopenia (< 0.5 x 10(9)/l) being observed in 26 of 38 patients. Three cases of National Cancer Institute grade 3 or 4 nephrotoxicity (serum creatinine, > 3 times the normal value) and three cases of grade 3 or 4 central nervous system toxicity were reported. Overall, three complete and five partial responses were achieved, for a major response rate of 21%. The median survival of all patients was 11 months. We conclude that ifosfamide-based chemotherapy can produce objective responses in previously treated patients with metastatic soft-tissue sarcoma but that cisplatin increases the toxicity of therapy. Phase II trials of new agents are needed to identify drugs with clinical activity in the treatment of soft tissue sarcomas. PMID- 8453702 TI - A pilot study of rapidly alternating epirubicin/dacarbazine and ifosfamide as first-line therapy for metastatic soft-tissue sarcoma in adults. AB - Currently, anthracyclines and ifosfamide are the most effective drugs for the treatment of disseminated soft-tissue sarcoma. We designed a treatment protocol of rapidly alternating epirubicin/dacarbazine and ifosfamide for previously untreated soft-tissue sarcoma, whereby 100 mg/m2 epirubicin was given on day 1, 500 mg/m2 dacarbazine was given on days 1 and 2, and 6,000 mg/m2 ifosfamide given via 24-h infusion was begun on day 15. The entire treatment cycle was scheduled to begin again on day 28 if the leukocyte count had reached 3.0 x 10(9)/l. From June 1988 to May 1991, a total of 28 patients were enrolled in the study. Eight patients (31%) achieved a partial response to therapy. The median duration of partial response was 8.5 months, and the median time to progression for all patients was 5 months. Myelosuppression was dose-limiting (leukocyte nadir, 1.7 x 10(9)/l; platelet nadir, 70 x 10(9)/l). Prolonged myelosuppression forced frequent therapy delays; therefore, only 74% of the planned doses could be given. The nonhematologic toxicity was tolerable. This rapidly alternating treatment protocol was determined to offer no therapeutic advantage over anthracycline therapy either alone or in combination with dacarbazine in terms of response rate or time to disease progression. The inclusion of hematopoietic growth factors, however, might ameliorate the dose-limiting myelosuppression and permit the administration of higher doses. PMID- 8453703 TI - Ifosfamide plus epirubicin at escalating doses in the treatment of locally advanced and/or metastatic sarcomas. AB - A total of 46 consecutive patients were entered into this study to assess the efficacy and toxicity of an epirubicin/ifosfamide combination in treating locally advanced and/or metastatic adult sarcomas (38 soft-tissue sarcomas and 7 bone sarcomas in 45 evaluable patients). Epirubicin was given at escalating doses (from 50 to 100 mg/m2) as an intravenous (i.v.) bolus on day 1, and ifosfamide was given i.v. at 1.2 g/m2 daily on days 1-5. Cycles were repeated every 4 weeks. The overall response rate was 38% (17 of 45 patients), reaching 42% (16 of 38) in the soft-tissue sarcoma group and 44% (17 of 39) in patients who had not been treated previously. In all, 4 complete responses (CRs, 9%) and 13 partial responses (PRs, 29%) were obtained. Most responses (about 68%) were reached within the first 2 cycles. The high-dose intensity of epirubicin (P < 0.04), the histologic type (P < 0.03), the presence of metastatic lesions only (P < 0.01), and the lack of previous treatment (P < 0.04) were found to be positively correlated with the probability of response. The median duration of response was 8 months. The median survival period was 10 months for all evaluable patients and 21 months for those achieving CRs and PRs (P < 0.01). The tumor grade, performance status, and extent of disease at entry into the study correlated with survival. The treatment was well tolerated; no case of sepsis occurred, and neither acute nor cumulative cardiotoxicity was observed. Epirubicin in combination with ifosfamide is therefore effective in advanced and/or metastatic disease with acceptable toxicity. The activity of this combination as compared with that of either of the two drugs given alone at optimal doses needs to be evaluated in prospective randomized trials. PMID- 8453704 TI - Perspectives on anthracyclines plus ifosfamide in advanced soft tissue sarcomas. AB - Doxorubicin and ifosfamide are currently the two main drugs for the treatment of soft tissue sarcomas in adults. Given in combination at full doses, with or without dacarbazine, these agents have induced higher response rates than were obtained with single-agent therapy. Because they involve considerable myelotoxicity, however, full-dose regimens should be reserved for patients with good performance status and without potential septic foci. Obviously, higher response rates do not automatically translate into improved survival. In soft tissue sarcomas, full-dose polychemotherapy will most probably provide a survival benefit only in selected patients in whom surgery can be performed in combination with chemotherapy. Prospective trials in such patients, although difficult to carry out, would be highly desirable. The information they would provide might help the clinician tailor treatment in a more rational way and improve chances of cure or long-term survival in at least some patient subgroups. PMID- 8453705 TI - Preoperative systemic etoposide/ifosfamide/doxorubicin chemotherapy combined with regional hyperthermia in high-risk sarcoma: a pilot study. AB - From November 1990 to September 1991, 23 adults with high-risk, nonmetastatic sarcomas (20 soft-tissue sarcomas and 3 chondrosarcomas) were entered in a pilot protocol (RHT-91) involving regional hyperthermia combined with systemic chemotherapy followed by surgery. Of these patients, 12 had undergone previous surgery and/or radiation, 5 had received previous multidrug chemotherapy, and 6 were previously untreated. A tumor size of > 8 cm and/or an extracompartmental tumor location (11 patients) or local recurrence (12 patients) were defined as high-risk factors in addition to tumor grading (21 patients had grade 2 or 3 sarcomas). Regional hyperthermia was produced by an electromagnetic deep-regional heating device. For systemic chemotherapy, all patients received etoposide/ifosfamide/doxorubicin (EIA) and mesna, with regional hyperthermia being given only on days 1 and 4 in repeated EIA/regional hyperthermia cycles every 3 weeks. Tumor temperatures (range, 40 degrees-44 degrees C) were measured by invasive thermometry in all patients during each regional hyperthermia treatment. A total of 181 regional hyperthermia treatments were applied within the pelvic region (11 patients) or extremities (12 patients) bearing relatively large tumors (mean volume, 848 cm3). By the cutoff date for this analysis (October 15, 1991), 13 patients had undergone surgery after receiving 2-6 (mean, 3.8) cycles of EIA chemotherapy combined with regional hyperthermia; all tumors except one were resected without disfiguration. In 22 evaluable patients (minimum, 2 EIA plus regional hyperthermia cycles), the clinical response rate was 27%, with 6 patients showing partial responses (PRs). In addition, a pathologic response to preoperative thermochemotherapy was evaluable in 13 patients, with 4 responders (31%) having > 50% histologic necrosis. In all, 3 of the responders (1 PR and 2 patients with > 50% histologic necrosis) relapsed within 3 months of surgical resection. The other 7 responding patients (5 PRs and 2 patients with > 50% histologic necrosis) showed stable disease with local tumor control. The study (RHT-91) is continuing as a multicenter phase II trial (opened on November 19, 1991) in patients with high-risk soft-tissue sarcomas to test the potential of preoperative thermochemotherapy in regard to local control and survival. PMID- 8453706 TI - Efficacy of ifosfamide in combination with doxorubicin for the treatment of metastatic soft-tissue sarcoma. The Eastern Cooperative Oncology Group. AB - On the basis of ifosfamide's demonstrated single-agent activity in adult soft tissue sarcoma, the Eastern Cooperative Oncology Group (ECOG) tested whether ifosfamide would add to the efficacy of doxorubicin in a three-regimen, controlled phase III trial. Doxorubicin, ECOG's standard to which newer chemotherapeutic treatments are compared, was given at a dose of 80 mg/m2 every 3 weeks and was designated the control regimen. Ifosfamide was given at a dose of 3,750 mg/m2 on days 1 and 2 every 3 weeks in combination with 30 mg/m2 doxorubicin given each day for 2 days; additionally, mesna was given to counter the genitourinary toxicity associated with ifosfamide. A second experimental regimen consisted of doxorubicin (40 mg/m2), mitomycin (8 mg/m2), and cisplatin (60 mg/m2), all given intravenously on day 1, with repeated cycles being scheduled for day 21. Of the 279 adults with soft-tissue sarcoma who were entered in the study, 260 were analyzed. The overall response rate was 20% for doxorubicin, 34% for ifosfamide/doxorubicin, and 31% for doxorubicin/mitomycin/cisplatin, with the difference between the first two regimens being significant (P = 0.04). The median survival was 8.8, 11.5, and 9 months, respectively, for the three regimens. Myelosuppression, the predominant toxicity, occurred in 60%, 88%, and 58% of patients, respectively. PMID- 8453707 TI - The use of recombinant human granulocyte-macrophage colony-stimulating factor with combination chemotherapy in the treatment of advanced adult soft-tissue sarcomas: early results from the EORTC Soft-Tissue and Bone Sarcoma Group. AB - We gave the "optimal" dose of doxorubicin (75 mg/m2) with ifosfamide (5 g/m2), the two most active agents against metastatic soft-tissue sarcomas, in an attempt to determine the feasibility of administration of these doses in combination. To offset complications arising from the myelosuppression associated with this regimen, recombinant human granulocyte-macrophage colony-stimulating factor (rhGM CSF, 250 micrograms/m2 daily) was given by subcutaneous injection during the intervals between courses of chemotherapy. In all, 111 patients with progressive metastatic soft-tissue sarcoma were entered, 104 of whom were eligible for preliminary analysis. Use of rhGM-CSF allowed full doses of chemotherapy to be given to the majority of patients, although cumulative thrombocytopenia became a dose-limiting toxicity during subsequent courses. Two treatment-related deaths occurred, one from presumed septicemia while the patient was at home and one as a result of cardiac failure. An overall response rate of 45% was achieved. The activity of this high-dose combination (with rhGM-CSF) will be compared with that of standard treatment doses in a future phase III randomized trial. PMID- 8453708 TI - Different patterns of regulation of the genes encoding the closely related 56 kDa selenium- and acetaminophen-binding proteins in normal tissues and during carcinogenesis. AB - A full-length cDNA encoding a 56 kDa liver protein recently implicated in the detoxification of acetaminophen (AP56) has been cloned by virtue of its similarity to the 56 kDa selenium-binding protein (SP56): in fact, the deduced AP56 amino acid sequence differs at only 14 residues from SP56. Isolation of genomic DNA recombinants from a Balb/c mouse cosmid genomic DNA library shows that SP56 and AP56 are encoded by two different genes. Using reverse transcription/PCR with oligonucleotide primers that distinguish the AP56 and SP56 mRNAs shows that the SP56 mRNA is highly expressed in liver, kidney and, to a lesser extent, lung; whereas the AP56 mRNA is mainly expressed in liver. Both mRNAs tend to be down-regulated in liver cell lines but remain high in DEN induced liver tumours in vivo. The relevance of these findings is evaluated in terms of the postulated functions of the two proteins in mediating the anti carcinogenic effects of selenium and detoxification mechanisms. PMID- 8453709 TI - Metabolism of the carcinogen N-hydroxy-N-2-fluorenylacetamide by rat peritoneal neutrophils. AB - The in vitro metabolism of a locally carcinogenic N-hydroxy-N-2 fluorenylacetamide (N-OH-2-FAA) by rat peritoneal polymorphonuclear leukocytes (PMNL), chiefly neutrophils, elicited with intraperitoneal injections of proteose peptone, was examined. At 10(6) PMNL/ml in media containing halide (X-), 0.14 M Cl- +/- 0.1 mM Br- (without Ca++ and Mg++), addition of 10 nM phorbol myristate acetate (PMA) resulted in generation of superoxide anion and H2O2. Subsequent cetyltrimethylammonium Cl- (Cetac) addition at 0.002% effected myeloperoxidase (MPO) activity release. PMNL treated with PMA and/or Cetac did not metabolize N OH-2-FAA (30 microM). However, 1-2 pulses of H2O2 (50 microM) after Cetac addition resulted in oxidation of N-OH-2-FAA to N-acetoxy-2-FAA (< 0.5 microM) and 2-nitrosofluorene (2-NOF) (1-2 microM). In the presence of Br- 2-NOF was increased (3-5 microM). The results are consistent with oxidation of N-OH-2-FAA by MPO/H2O2 and MPO/H2O2/X- via two pathways: one electron oxidation leading to N acetoxy-2-FAA and 2-NOF, and X(-)-dependent oxidation to 2-NOF. N-Acetoxy-2-FAA (10 microM) incubated with PMNL under similar conditions was converted non enzymatically to 4-OH-2-FAA (< or = 5 microM) and enzymatically to N-OH-2-FAA (< or = 3 microM). In the presence of H2O2, smaller amounts of these products were formed. Formation of N-OH-2-FAA was prevented by paraoxon (0.1 mM) suggesting O deacetylase activity. However, accountability for N-acetoxy-2-FAA decreased with time, presumably because of binding to cellular macromolecules. With H2O2 addition, 2-NOF (10 microM) was converted to 0.5 or 0.25 microM 2-nitrofluorene by active PMNL or heat-inactivated cell lysates, respectively. Low recoveries of 2-NOF were also attributed to binding. The results suggest that PMNL may be involved in activation of the carcinogenic N-arylhydroxamic acids in vivo. PMID- 8453710 TI - Covalent binding of styrene to DNA in rat and mouse. AB - Covalent binding of [7-3H]styrene (S) to DNA in vivo was measured and evaluated in a quantitative manner in order to investigate whether DNA adduct formation could form a mechanistic basis for tumor induction in a carcinogenicity bioassay. [7-3H]S was administered by inhalation in a closed chamber to male and female CD rats and B6C3F1 mice. After 4.5-6 h (rats) and 6-9 h (pools of four mice), S doses of 23-39 and 85-110 mg/kg respectively had been metabolized. DNA was purified to constant specific radioactivity which was measurable in all samples. DNA was enzymatically degraded to the 3'-nucleotides which were separated by HPLC for the detection of radiolabeled nucleotide-S adducts. The fractions with the normal nucleotides contained most of the radioactivity. In mouse liver DNA, a minute but significant level of adduct radioactivity was also detected. In the units of the Covalent Binding Index CBI = (mumol adduct/mol DNA nucleotide)/(mmol chemical/kg body wt), values of 0.05-0.09 and 0.07-0.18 were calculated for males and females respectively. In the rat, no DNA adducts were detectable in the liver at a limit of detection of 0.1 CBI units. Two of the four lung samples of the female rats showed adduct-related radioactivity corresponding to 0.07 CBI units. The CBI values are compatible with styrene 7,8-oxide as the reactive intermediate. The data are compared with CBI values and carcinogenic potencies of established genotoxic carcinogens. It is concluded that the DNA-binding potency of S is so low that significant tumor induction in a standard bioassay for carcinogenicity is unlikely to be due to DNA adduct formation alone. Consequences for a human risk estimation are discussed. PMID- 8453711 TI - Protection against 12-O-tetradecanoylphorbol-13-acetate-caused inflammation in SENCAR mouse ear skin by polyphenolic fraction isolated from green tea. AB - Earlier studies conducted in our laboratory have shown that a polyphenolic fraction isolated from green tea (GTP) possesses anti-skin tumor initiating and anti-skin tumor promoting activity in the two-stage skin tumorigenesis protocol in SENCAR mouse. We have also shown that topical application of GTP inhibits tumor promoter-caused induction of epidermal ornithine decarboxylase activity in SENCAR mice in a dose-dependent manner, and that its oral feeding in drinking water to SKH-1 hairless mice enhances antioxidant and phase II enzyme activity in liver, lung, small bowel and skin. In this study, we show that single or multiple applications of GTP on SENCAR mouse ear prior to or after the application of 12-O tetradecanoylphorbol-13-acetate (TPA) afford significant protection (P < 0.05) against TPA-induced edema. Pre-application of GTP also afforded significant protection against TPA-induced hyperplasia in the ear skin. The percentage protection by GTP both in terms of epidermal thickness and vertical cell layers was 75 and 90% respectively (P < 0.005). In further studies, we assessed the protective effect of GTP against TPA-caused infiltration of neutrophils in the ear skin of SENCAR mouse, by determining a naturally occurring constituent of neutrophils, myeloperoxidase, as a quantitative marker of tissue neutrophil content. Prior application of GTP resulted in significant protection against TPA caused infiltration of neutrophils (P < 0.005). These results suggest that GTP possesses potential as a cancer chemopreventive agent against stage I tumor promotion. PMID- 8453712 TI - Differential co-promoting activities of alpha, beta and gamma interferons in the murine skin two-stage carcinogenesis model. AB - SENCAR mice develop more papillomas in two-stage skin carcinogenesis protocols if gamma interferon (IFN-gamma) is co-administered with 12-O-tetradecanoylphorbol-13 acetate (TPA) during the promotion phase. In the current study preparations of murine alpha, beta and gamma IFNs were surveyed for their abilities to modulate TPA-dependent promotion and induction of epidermal hyperplasia, inflammation and ornithine decarboxylase activity (ODC). Single or multiple i.p. administrations of IFN-alpha, -beta or -gamma (< or = 2500 units) did not induce epidermal hyperplasia, inflammation or ODC activity. Single or multiple i.p. administrations of IFN-alpha, -beta or -gamma (2500 units) to mice being topically promoted with 0.1 or 1 microgram of TPA did not alter the epidermal hyperplasia induced by the phorbol ester. The vascular permeability of the skin, as evaluated by the extravasation of Evans blue dye, was increased in a dose dependent fashion by TPA over the range of 0.1-1 microgram. Treatment of mice promoted with 0.1 microgram of TPA with IFN-gamma (> or = 2500 units) significantly increased the skin's vascular permeability. Comparable effects were not obtained with IFN-beta (IFN-alpha not tested). Treatment of TPA-promoted mice with IFN-gamma, and to a lesser extent IFN-beta, weakly potentiated the TPA dependent induction of epidermal ODC activity. Under conditions in which IFN gamma had co-promoting activities in an initiation-promotion protocol, co treatment of initiated mice with 1 microgram of TPA and IFN-alpha or -beta (100 5000 units) did not reproducibly alter tumor latency., or papilloma and carcinoma multiplicities. These findings suggest that the co-promoting activities of IFNs are restricted to the gamma class, and are not uniformly reflected by parameters commonly employed as short-term markers of tumor promotion. PMID- 8453713 TI - Mutational specificity of the (+)-anti-diol epoxide of benzo[a]pyrene in a supF gene of an Escherichia coli plasmid: DNA sequence context influences hotspots, mutagenic specificity and the extent of SOS enhancement of mutagenesis. AB - Mutagenesis by the suspected major mutagenic metabolite of activated benzo[a]pyrene, which is (+)-anti-BPDE, was analyzed with a new system, which permits the selection of supF- mutations in an Escherichia coli plasmid using lactose minimal plates. (+)-anti-BPDE enhances base pairing mutations- principally at G:C base pairs, frameshift mutations and large deletions. Frameshift mutagenesis principally involves deletions and insertions of a single G:C base pair in runs of G:C base pairs. Base pairing mutations are significantly enhanced by SOS induction, especially GC-->TA mutations. Nearest neighbor analysis was performed assuming that a guanine (underlined) is being mutated, and (+)-anti-BPDE base pairing mutagenesis is enhanced by SOS induction in 5'-(A/T)G 3' sequences approximately 4-fold more than in 5'-(G/C)G-3' sequences, and in 5' G(C/G)-3' sequences approximately 4-fold more than in 5'-G(A/T)-3' sequences; this is discussed. The influence of sequence context on quantitative aspects of (+)-anti-BPDE mutagenesis is considered, and hotspots are found at most, but not all, 5'-GG-3' sequences. The influence of sequence context on qualitative aspects of (+)-anti-BPDE mutagenesis (i.e. mutagenic specificity) is also considered. For example, the sequences, 5'-AG-3', 5'-CG-3' and 5'-GG-3', all have examples of G- >T, G-->A and G-->C mutations, while in the sequence, 5'-TG-3', only G-->T mutations have been detected. (The latter finding correlates with a recent site specific study on the major adduct of (+)-anti-BPDE formed at N2-Gua in a 5'-TG 3' context, where G-->T mutations predominated [Carcinogenesis (1992) 13, 1415 1425].) These results suggest that sequence context plays a role in defining the kind of mutation (i.e. GC-->TA versus GC-->AT versus GC-->CG) induced by (+)-anti BPDE, where the base on the 5' side of the guanine undergoing mutation seems to be influential. The most likely model for this is that sequence context influences adduct conformation, which controls mutagenic specificity. PMID- 8453714 TI - Lack of peroxisomal enzyme inducibility in rat hepatic preneoplastic lesions induced by mutagenic carcinogens: contrasted expression of glutathione S transferase P form and enoyl CoA hydratase. AB - While glutathione S-transferase P form (GST-P), a reliable marker for preneoplastic lesions induced by mutagenic hepatocarcinogens, is generally not expressed in rat liver foci, hyperplastic nodules and hepatomas induced by peroxisome proliferators (PPs), such lesions can be detected due to their peroxisomal enzyme-negative nature. For comparative purposes we examined the inducibility of enoyl CoA hydratase (ECH), a key peroxisomal enzyme, in rat hepatic preneoplastic lesions induced by mutagenic carcinogens. Clofibrate (CF) was therefore administered for 2 or 4 weeks following performance of the Solt Farber protocol using diethylnitrosamine and 2-acetylaminofluorene. Immunohistochemical examination revealed no or only very weak expression of ECH within the induced foci in clear contrast to the strong staining of surrounding parenchyma. ECH expression was thus diametrically opposed to that of GST-P which was found only in foci. Although ECH was completely lacking in GST-P-strongly positive foci, it was expressed in GST-P-negative hepatocytes inside some foci otherwise positive for GST-P. CF administration resulted in a significant decrease in the numbers and areas of foci exhibiting strongly positive or positive GST-P staining; this being reflected in a lowering of GST-P protein levels. Furthermore, in primary cultured rat hepatocytes, clofibric acid as well as dexamethasone suppressed the expression of both GST-P and the oncogene, c-jun. These results taken together suggest that possible interaction of the PP receptor with JUN might be involved in loss of ECH expression in GST-P-strongly positive foci. PMID- 8453715 TI - Elevated ornithine decarboxylase activity, polyamines and cell proliferation in neoplastic and vacuolated liver cells of winter flounder (Pleuronectes americanus) AB - Liver neoplasms, including hepatocellular and cholangiocellular tumors, commonly occur in winter flounder (Pleuronectes americanus) caught from some chemically contaminated areas such as Boston Harbor. Hydropically vacuolated cells, very often associated with neoplasia in winter flounder liver, appear to represent the first cellular abnormality in animals that later develop frank neoplasms. The proliferative capacity of hydropically vacuolated cells was studied by analyzing both ornithine decarboxylase (ODC) activity and bromodeoxyuridine (BrdU) labeling indices. Liver of winter flounder with vacuolated cellular lesions had ODC activity more than 5- to 12-fold greater than that in liver that lacked such vacuolation, whether caught from Boston Harbor or Georges Bank. Large focal areas of hydropically vacuolated cells dissected from severely affected livers had ODC activity as high or higher than surrounding parenchymal tissue. Significant elevations in hepatic polyamine levels and ratios of putrescine/spermidine were also present in all Boston Harbor animals studied, especially those exhibiting vacuolated cellular lesions, as compared to Georges Bank fish. BrdU labeling techniques indicate that hydropically vacuolated cells, along with perivacuolar small basophilic cells and neoplastic cholangiocytes, appear to have the capacity to synthesize DNA and undergo mitosis. The frequent association of hydropically vacuolated cells with hepatic neoplasia, along with high ODC activity and DNA synthesis capability, suggest that the vacuolated cells and/or perivacuolar basophilic cells may be integral to the development of some neoplastic phenotypes in winter flounder liver. PMID- 8453716 TI - Effect of diallyl sulfide on aristolochic acid-induced forestomach carcinogenesis in rats. AB - In this study the development of aristolochic acid (AA) induced tumors in rats with and without diallyl sulfide (DAS) was studied. Experiments were also conducted to establish the effects of DAS administration on AA-derived DNA single stranded regions and DNA adduct formation in the forestomach of such animals. Forestomach, urinary bladder and thymus tumors were induced in male BD-6 rats after oral treatment for 12 weeks with AA (2 x 10 mg/kg/week). Administration of 150 mg/kg DAS intragastrically 4 h prior to AA treatment reduced significantly the number of rats that developed forestomach tumors (6-9 months after the start of experiment). The incidence of AA-induced forestomach tumors was 10% (two out of 20 rats) after co-administration of DAS and 60% (12 out of 20 animals) when AA was administered alone. The high dose of DAS (2 x 150 mg/kg) markedly inhibited the formation of squamous cell carcinomas in the forestomach. However, the thioether did not prevent the formation of forestomach and urinary bladder papillomatosis. Additionally, DAS co-administration decreased the accumulation of single-stranded regions in rat forestomach DNA. Using the nuclease P1 enhancement method of the 32P-postlabeling assay, a decrease in the level of AA-derived adducts was also detected after co-administration of DAS. We conclude that the decrease of DNA damage after DAS co-administration is associated with the delay in conversion of papillomas to malignant forestomach tumors. PMID- 8453717 TI - 12-O-tetradecanoylphorbol-13-acetate-mediated systemic co-promotion in the murine skin multistage carcinogenesis protocol. AB - The systemic promoting and co-promoting activities of 12-O-tetradecanoylphorbol 13-acetate (TPA) were examined in a murine skin multistage carcinogenesis protocol. The dorsal skins of female inbred SENCAR (SSIN) mice were initiated with 25 nmol of 7,12-dimethylbenz[a]anthracene (DMBA). Topical treatment of initiated dorsal skin with 20 mg of benzoyl peroxide (BzP) promoted the eventual development of 8-15 dorsal papillomas per mouse. Repeated application of 2 micrograms of TPA to the ventral skins of dorsally initiated mice did not promote the formation of dorsal tumors. However, the latency of dorsal papilloma development was significantly decreased in initiated mice treated with 0.4 or 2 micrograms TPA (ventral application) and promoted with BzP (dorsal application). The co-promoting effects of topically applied TPA could not be mimicked by administering the promoter i.v. Only 6/23 initiated, BzP-promoted SSIN mice developed squamous cell carcinomas (SCC) during a 61 week promotion period. In contrast, during the same time-frame 12/24 and 11/24 BzP-promoted mice cotreated with 2 or 0.4 microgram of TPA developed SCC respectively. Repeated application of 2 micrograms of TPA to the ventral skins of dorsally initiated mice resulted in the development of ventral tumors. Ventral tumor incidence and multiplicities could be dramatically reduced by housing the mice individually, as opposed to collectively, for a day following initiation. Collectively these findings suggest that TPA can function as a co-promoter in the murine skin multistage carcinogenesis model through a systemic mechanism. The systemic co-promoting activity may be mediated by a factor(s) produced by the skin in response to TPA exposure. Furthermore, inter-mouse transfer of topically applied initiator from one cutaneous site to another occurs as a consequence of the huddling habits of mice. PMID- 8453718 TI - Cyproterone acetate generates DNA adducts in rat liver and in primary rat hepatocyte cultures. AB - Cyproterone acetate (CPA), an active component of certain contraceptive and antiandrogenic drugs, has been shown recently to induce DNA repair synthesis in rat hepatocytes in vitro. In the present study we examined whether CPA can cause the formation of DNA adducts detectable by the 32P-postlabeling technique in hepatic cells in vitro and in vivo. Incubation of primary cultures of hepatocytes from male Wistar rats with CPA resulted in the occurrence of radioactive spots in the radiochromatograms of 32P-postlabeled DNA digests indicating the formation of two DNA adducts ('A' and 'B'). At 30 microM CPA, the highest concentration tested, approximately 50 'A' adducts and five 'B' adducts were found per 10(9) nucleotides. DNA of hepatocyte cultures from female rats was found to contain adduct A and a minor adduct termed 'D', but adduct B was not observed. Between 1 and 10 microM CPA, the relative level of adduct A was approximately 20-fold higher than the level observed in male hepatocytes. In vivo DNA adducts were detected almost exclusively in hepatic DNA. Hepatic DNA from male Wistar rats treated with single doses of CPA (1-100 mg/kg) by gavage, showed the major adducts A and B and two further spots of minor intensity ('C' and 'D') in the radiochromatograms. No adducts were detectable in extrahepatic tissues. The adduct pattern of liver DNA from females exposed to single oral doses between 0.1 and 30 mg CPA/kg body wt was similar to that observed in males; however, the relative levels for adducts A and D were approximately 100-fold higher. In females, linear relationships between dose and adduct levels were observed for all four adducts. The present findings show that CPA causes damage to hepatic DNA not only in vitro, but also in vivo. Thus it appears possible that DNA adduct formation is involved in the formation of hepatic tumors during long-term treatment of rats with the synthetic steroid. PMID- 8453719 TI - Inhibition of lead chromate clastogenesis by ascorbate: relationship to particle dissolution and uptake. AB - Chromium metal salts are considered to be human carcinogens, especially the salts of low solubility. Lead chromate, a highly insoluble chromium metal salt, has been shown to be tumorigenic, genotoxic and clastogenic. In this study, the roles of particle-cell contact, particle dissolution and particle uptake in the clastogenic activity of lead chromate were investigated. Using Pb51CrO4 it was found that lead chromate particles (1.2 microns mean diameter, -28 mV surface charge) were slightly soluble in water; solubility increased 2-fold when particles were incubated in culture medium, but was not increased further by the addition of serum. The extracellular concentration of chromium increased 7-fold when lead chromate was incubated in the presence of Chinese hamster ovary (CHO) cells compared with culture medium alone. The intracellular concentration of ionic chromium increased in a dose-dependent manner following exposure of CHO cells to clastogenic doses of lead chromate reaching estimated levels as high as 1.2 mM per cell. Treatment of cells with lead chromate particles in the presence of a nontoxic dose of vitamin C blocked uptake of ionic chromium and eliminated the clastogenic activity of the particles. Transmission electron microscopy showed that lead chromate particles were internalized by CHO cells in phagocytic vacuoles in as little as 1 h; internalization was unaffected by co-treatment with vitamin C. It was demonstrated that particle-cell contact was required for lead chromate-induced clastogenesis. These data show that although phagocytic particle uptake occurs, particle-cell contact and extracellular dissolution are responsible for the clastogenic activity of lead chromate. These data also demonstrate that the genotoxicity of particulate hexavalent chromates can be blocked by vitamin C. PMID- 8453720 TI - Vinyl carbamate epoxide, a major strong electrophilic, mutagenic and carcinogenic metabolite of vinyl carbamate and ethyl carbamate (urethane). AB - Vinyl carbamate epoxide (VCO) was found to possess strong electrophilic, mutagenic and carcinogenic activities. It reacted with water at 37 degrees C and pH 7.4 (phosphate buffer) to form glycolaldehyde and several related reducing compounds; none of these products were mutagenic for Salmonella typhimurium TA1535. Under these conditions VCO had a half-life (determined chemically and mutagenically) of approximately 10.5 min. This half-life was progressively lowered by increasing concentrations of chloride ion (liver, serum and isotonic levels). This ion reacted with VCO to form chloroacetaldehyde. VCO also reacted with other nucleophiles such as glutathione, DNA and its constituent guanine and adenine bases. The purine adducts formed by VCO in DNA in vitro and in vivo were released by weak acid treatment and consisted of 7-(2'-oxoethyl)guanine and N2,3 ethenoguanine as major products with 1,N6-ethenoadenine as a minor product. VCO was a strong direct mutagen in Salmonella typhimurium TA1535 and TA100 but was only weakly active in the TA98 mutant. VCO was a stronger initiator of carcinogenesis in the skin of CD-1 mice and in the liver of infant male B6C3F1 mice than its metabolic precursors vinyl carbamate (VC) and ethyl carbamate (EC). Unlike VC and EC, VCO was a strong complete carcinogen in the skin of CD-1 mice and induced papillomas and carcinomas following repetitive administration of sub ulcerogenic doses. VCO also exhibited some carcinogenic activity in the lungs of mice and in the s.c. and mammary tissue of female Sprague-Dawley rats. These data and those from other recent studies support the conclusion that VCO is a major strong electrophilic, mutagenic and carcinogenic metabolite of EC and VC in the mouse. PMID- 8453721 TI - K-ras and p53 point mutations in 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induced hamster lung tumors. AB - Lung tumors were induced in Syrian golden hamsters by s.c. injection of 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). After 40 weeks lung tumor tissue was isolated. Administration of the NNK and exposure of the animals to an atmosphere of 65% oxygen resulted in a statistically significant reduction in tumor size but did not alter the histological tumor type or tumor incidence when compared with carcinogen treated animals maintained under ambient air. Histologically, lung tumors had the morphologic features of adenomas and adenocarcinomas with approximately 15% being squamous cell carcinomas. Lung tumors were examined for mutations in the Ki-ras oncogene and the p53 tumor suppressor gene by direct sequencing. The Ki-ras mutation frequency in RNA isolated from pooled tumors and in DNA isolated from individual tumors were found to be identical. Activated Ki-ras alleles were detected in 77-94% of tumors. All mutations observed (from a total of 65) except one were GC-AT. The Ki-ras mutations resulted in amino acid substitutions at either codons 12 or 13. No mutations were detected at the 61st codon. Examination of the same tumors for p53 mutations showed only one point mutation. We conclude that the NNK treatment in Syrian golden hamsters results in a distinctive mutation pattern in the Ki-ras gene whereas p53 gene mutations may not play a major role at this stage in hamster lung tumorigenesis. PMID- 8453722 TI - Effects of sodium butyrate on DNA content, glutathione S-transferase activities, cell morphology and growth characteristics of rat liver nonparenchymal epithelial cells in vitro. AB - The effects of sodium butyrate, which has been shown to act as a differentiation promoting agent in several different tumor cell lines, were studied in a rat liver nonparenchymal epithelial cell line. Exposure of these cells to 3.75 mM butyrate resulted in an inhibition of cell proliferation and, at the same time, an increase in cell diameter (2- to 6-fold) and size of the nuclei (approximately 2-fold) after 3 days in culture. Binucleated cells arose, comprising approximately 12% of the cells investigated, and the number of cells with an abnormal set of chromosomes was increased. Intercellular communication, measured by dye transfer of Lucifer Yellow, was unchanged. From the various xenobiotic metabolizing enzyme activities measured, only those of glutathione S-transferases were significantly altered (increases of 4- to 9-fold) by butyrate treatment. These increases were mainly due to the predominant rise in the pi class isoenzyme which is a well-known tumour marker in rat hepatocarcinogenesis. Thus, our results cannot be interpreted as being either due to promotion of differentiation or due to transformation. The state and type of cell under study has to be considered and investigations of further differentiation parameters are needed to obtain a deeper insight into the biological activity and the underlying mechanisms of cell state modifying agents like butyrate. PMID- 8453723 TI - Formation and repair of benzo[a]pyrene-DNA adducts in cultured hamster tracheal epithelium determined by 32P-postlabeling analysis and unscheduled DNA synthesis. AB - Hamster tracheal organ cultures were used to investigate the relationship between DNA adduct formation measured directly by the 32P-postlabeling assay, and the DNA damage measured indirectly by the unscheduled DNA synthesis (UDS) assay. Hamster tracheas were treated with three concentrations of benzo[a]pyrene (B[a]P) for 2 days. Postlabeling and UDS assays were also carried out a few days after removal of the B[a]P. Furthermore, the types of B[a]P-DNA adducts formed in the in vitro organ culture were qualitatively compared with those formed in vivo after intratracheal intubation of B[a]P attached to Fe2O3 particles. In vivo only one adduct was detected by 32P-postlabeling. This adduct cochromatographed with the trans-addition produce of dG and (+)-anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10 tetrahydrobenzo[a]pyrene (BPDE). In vitro, a clear B[a]P-DNA adduct pattern was also found with the 32P-postlabeling assay. Four different adducts were found. The main adduct spot migrated to the same position on the thin-layer chromatogram as the in vivo adduct. B[a]P-DNA adduct formation was both time- and dose dependent. During the first day after removal of B[a]P the adduct levels still increased, thereafter they decreased at all B[a]P concentrations. A time- and dose-dependent increase in UDS was observed in the tracheal epithelial cells treated with B[a]P in vitro. After removal of the B[a]P, UDS decreased immediately, in contrast to the formation of DNA adducts. The results of the present study show that B[a]P induces time- and dose-dependently both DNA adducts and UDS in hamster tracheal organ culture. Moreover, the main DNA adduct formed in vitro, dG-(+)-anti-BPDE, was the same as that found in vivo. PMID- 8453724 TI - Characterization of DNA adducts at the bay region of dibenz[a,h]anthracene formed in vitro. AB - Bay region diolepoxide-DNA adducts of dibenz[a,h]anthracene (DBA) formed in vitro were identified and their absolute stereochemistry was assigned. After activation of [5,12-14C]DBA with liver microsomes obtained from Aroclor 1254 treated male Sprague-Dawley rats in the presence of calf thymus DNA for 1 h, the amount of DNA adducts was found to be 9.9 +/- 2.4 pmol/mg DNA, calculated on the basis of the portion of radioactivity eluted from the HPLC reversed-phase column with a water/acetonitrile gradient. Bay region diolepoxide-DNA adducts represented 27.5% of radioactivity associated with DNA adducts. The absolute configuration of the various adducts was determined from the reaction of the (+)- and (-)-3,4 dihydrodiol after metabolic activation and the reaction of the anti- and syn-3,4 dihydroxy-1,2-epoxy-1,2,3,4-tetrahydrodibenz[a,h]anthracen e with DNA or with the individual deoxyribonucleotides. The main bay region adduct was identified as a deoxyguanosine adduct of (anti)-3S,4R-dihydroxy-1R,2S-epoxy-1,2,3,4 tetrahydrodibenz [a,h]anthracene, a metabolite of (-)-3,4-dihydroxy-3,4-dihydrodi benz[a,h]anthracene. Anti bay region diolepoxide-deoxyguanosine adducts of DBA contributed to 17.7% and syn diolepoxide-derived deoxyguanosine adducts to 5.8% of adduct-associated radioactivity. The amount of bay region deoxyadenosine adducts was calculated to be 4%. For six of probably eight different deoxyadenosine adducts absolute stereochemistry could be assigned. 32P Postlabelling experiments revealed a binding of 23 +/- 6 pmol/mg DNA for (-)-3,4 dihydrodiol and of 1.5 +/- 0.4 pmol/mg DNA for (+)-3,4-dihydrodiol of DBA. PMID- 8453725 TI - Transformation of human breast epithelial cells by chemical carcinogens. AB - The present study was carried out to determine whether human breast epithelial cells (HBEC) are transformed by chemicals that have been proven to be carcinogenic in other model systems. A spontaneously immortalized human breast epithelial cell line, MCF-10F, was treated with dimethylbenz[a]anthracene (DMBA), benzo[a]pyrene (B[a]P), N-methyl-N-nitrosoguanidine (MNNG) or N-methyl-N nitrosourea (NMU) for 24 h. MCF-7 and T24 malignant cell lines were used as positive controls. All the carcinogens induced alterations in both cell morphology and pattern of growth, increased growth rate and anchorage-independent growth in agar-methocel, which became evident by the 8th to 10th passages post treatment, at approximately 157 days in culture. Colonies formed in agar-methocel were isolated and expanded. The following clones were successfully grown: D1, D2 and D3, from DMBA, M4 from MNNG, and BP1, BP2, BP5, BP6, BP7, and BP10 from B[a]P treated cells. From clones BP1 and BP2, selected cell populations were isolated and the derived cell lines or clones were named BP1-E and BP2-B respectively; the D3-1 cell line was derived from clone D3. BP1 and BP1-E clones showed increased anchorage-independent growth, chemotaxis and invasiveness. Clone D3-1 showed increased chemotactic and invasive capabilities, but to a lesser degree than BP1 E. The tumorigenic potential of the cells was tested by inoculation into SCID mice. MCF-7, T24 and BP1-E cells formed tumors in 100% of the SCID mice at 28, 10 and 101 days of inoculation respectively. None of the other clones formed tumors. It was concluded that both polycyclic hydrocarbons and aromatic amines induced in the immortal cells MCF-10F changes indicative of neoplastic transformation. Our data show that the phenotypes associated with neoplastic transformation appear in a progressive fashion, and that the emergence of clones is associated with the expression of higher proliferative rate, anchorage independence, chemotactic and chemoinvasive abilities and, in certain cases, tumorigenicity. PMID- 8453726 TI - Effect of turmeric and curcumin on BP-DNA adducts. AB - Many human cancers that are widely prevalent today can be prevented through modifications in life-styles, of which diet appears to be an important agent. Several dietary constituents modulate the process of carcinogenesis and prevent genotoxicity. Many plant constituents including turmeric appear to be potent antimutagens and antioxidants. Therefore the modulatory effects of turmeric and curcumin on the levels of benzo[a]pyrene induced DNA adducts in the livers of rats were studied by the newly developed 32P-postlabelling assay method. Turmeric when fed at 0.1, 0.5 and 3% and the active principle of turmeric (curcumin) when fed at a level of 0.03% in the diet for 4 weeks significantly reduced the level of BP-DNA adducts including the major adduct dG-N2-BP, formed within 24 h in response to a single i.p. injection of benzo[a]pyrene. The significance of these effects in terms of the potential anticarcinogenic effects of turmeric is discussed. Further, these results strengthen the various other biological effects of turmeric which have direct relevance to anticarcinogenesis and chemoprevention. PMID- 8453727 TI - p53 mutations in hepatocellular carcinomas induced by a choline-devoid diet in male Fischer 344 rats. AB - Analyses were performed on livers and hepatocellular carcinomas from male Fischer 344 rats fed a choline-devoid diet, to assess whether they carried alterations of the p53 tumor suppressor gene. The analyses consisted of immunoperoxidase staining of tissue sections with monoclonal antibodies to p53, Western blotting and cDNA sequencing. Immunostaining revealed the presence of mutant p53 proteins in 22/27 tumors analyzed and immunoblotting in 18/20. Immunochemical evidence was obtained that occurrence of the mutations precedes tumor development. cDNA sequencing was performed on 11 hepatocellular carcinomas that expressed mutant p53 gene proteins. Seven were found to contain point mutations within the 120-290 codon region of the gene, and one a microdeletion in the same region. No mutational hot spot was observed. It is concluded that mutations within the p53 gene, along with a c-myc gene amplification previously detected in these tumors, most likely contribute to the neoplastic transformation of liver cells in this nutritional model of hepatocarcinogenesis. The results are discussed also in view of recent literature on the presence of p53 mutations in human hepatocellular carcinomas. PMID- 8453728 TI - Mutational specificity of 2-nitro-3,4-dimethylimidazo[4,5-f]quinoline in the lacI gene of Escherichia coli. AB - 2-Nitro-3,4-dimethylimidazo[4,5-f]quinoline (NO2-MeIQ) is the nitro derivative of 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), one of the food pyrolysis product mutagens and carcinogens. The mutational specificity of NO2-MeIQ was determined using the lacI system in an Escherichia coli strain, EE125, harbouring the plasmid pKM101. NO2-MeIQ acts as a direct-acting mutagen towards this strain, and induces a broad range of mutational alterations. At higher doses; G:C-->T:A transversions dominate the mutational spectrum. Complex mutations were also observed, and the involvement of the SOS system in the processing of the mutations induced by NO2-MeIQ is suggested. PMID- 8453729 TI - Effect of heat processing and of vegetables and fruit in human diets on 1,2 dimethylhydrazine-induced colon carcinogenesis in rats. AB - The purpose of the present study was to investigate the modulating effect of heat processing and of vegetables and fruit in human diets on 1,2-dimethylhydrazine (DMH)-induced colon tumors. Groups of 36-45 male Wistar rats were fed for the whole experiment, starting at 4 weeks of age, one of the following diets: a semi synthetic animal diet (A, control); diet A to which vegetables and fruit were added (B); a raw human diet (meat, bread and eggs) supplemented with semi synthetic compounds (C); diet C with fried or baked products (D); a complete human diet consisting of heated products, and vegetables and fruit (E). The animal diets (A and B) contained 21.6% fat energy (E), 26.0% protein E, 52.4% carbohydrate E and 10.7% (w/w) fiber. The human diets (C, D and E) contained 40.6% fat E, 13.2% protein E, 46.2% carbohydrate E and 5% (w/w) fiber. Starting at 8 weeks of age and after 4 weeks of feeding the experimental diets, each rat was s.c. injected 50 mg/kg body wt, DMH for 10 weeks once weekly. At the end of the experiment, at the age of 9 months, all rats were killed and macroscopic abnormalities were collected. The colon was examined microscopically for tumors and lesions suspected of being tumors. The results revealed a lower incidence of adenomas in rats consuming the animal diet with vegetables and fruit (B) compared with the control animal diet (A). In contrast to the animal diets, vegetables and fruit added to fried or baked human diets showed no protection at all, but even increased the incidence of carcinomas. Heat processing alone had no significant effect on the DMH-induced tumor incidence. As the fat content and heat processing were main variables between the animal and human diets containing vegetables and fruit, the results obtained suggest that one of these factors or both influence the tumor-modulating effect of non-nutrient substances in vegetables and fruit. PMID- 8453730 TI - Carcinogenicity of catechol in F344 rats and B6C3F1 mice. AB - Carcinogenicity of catechol, a naturally occurring and industrial chemical which has been shown to have strong cell proliferating potential on rat glandular stomach epithelium, was investigated in male and female F344 rats and B6C3F1 mice. Groups of 30 male and female F344 rats and B6C3F1 mice were treated with 0.8% catechol in powdered diet continuously for 104 weeks (rats) or 96 weeks (mice). At necropsy, neoplastic lesions were observed mainly in the glandular stomach of both species. Adenomas were found in all rats and in the majority of mice: 29 out of 30 (97%) in males and 21 out of 29 (72%) females. In addition 15 out of 28 (54%) and 12 out of 28 (43%) of the male and female rats respectively, had well differentiated adenocarcinomas. No adenocarcinomas were found in mice of either sex. In the forestomach epithelium, although significant increase in papilloma development was not evident, incidences of squamous cell hyperplasia were significantly increased in rats and mice of both sexes. In other organs examined, incidence and numbers of liver hyperplastic foci per cm2 liver section were significantly lower in male rats. Although the incidence was not different, the numbers of hyperplastic foci were also significantly reduced in female rats. Thus the present experiment clearly demonstrated that catechol exerts carcinogenic activity in rodent glandular stomach epithelium. PMID- 8453731 TI - Effects of TPA on mitosis of V79 Chinese hamster cells. Reduced precision of chromosome distribution and modification of entrance into and exit out of mitosis. AB - Protein kinase C (PKC) was activated in V79 Chinese hamster cells with 10 nM 12-O tetradecanoylphorbol-13-acetate (TPA). Within 30 min soluble activity decreased concomitant with a 10-fold increase of particulate activity. The latter was still elevated after 3 h but was back to control levels after 24 h of treatment; by then soluble activity was lost. The frequency of mitotic cells with signs of abnormal spindle function increased within 15 min and reached a plateau after 45 60 min which lasted throughout the 4 h treatment. The c-mitotic effect was delayed and significantly lower when 10 nM TPA was combined with 50 microM of the protein kinase inhibitor H7. The frequency of disturbed mitotic cells decreased after 24 h of treatment but remained significantly higher than in non-treated cells. Change of medium and addition of new TPA caused a slight but significant further increase. It is suggested that PKC takes part in eliciting the c-mitotic effect of TPA. However, the sustained effect coincident with down-regulation points to significant alterations of the level or the activity of an as yet unidentified ultimate elicitor. TPA also caused a transient block in the G2 phase which was ameliorated by H7 and which could not be detected at all in TPA pretreated cells (24 h) given new TPA. This suggests that PKC takes part in eliciting the G2/M block as well but the mechanism is different from the one(s) behind the c-mitotic effect. V79 cells were found to exit from mitosis in the presence of 0.2 microgram/ml of colcemid but TPA-pretreated cells showed a decreased exit rate. There was no sign of hampered exit among cells going into mitosis soon after the G2 block was reversed, which implies that the spontaneous reversal of the block does not involve rapid down-regulation of PKC. PMID- 8453732 TI - Sex-dependent expression of class pi glutathione S-transferase during chemical hepatocarcinogenesis in B6C3F1 mice. AB - Expression of class pi glutathione S-transferase (GST-II) was investigated during chemical hepatocarcinogenesis in female and male mice. Diethylnitrosamine (DEN; 10 mg/kg body wt) was administered to B6C3F1 mice on day 15 after birth, and liver sections were immunohistochemically stained with GST-II antibody at 12 and 24 weeks thereafter. In the normal mouse liver, GST-II was strongly expressed in males but only weakly in females. At 24 weeks after DEN treatment, the majority of preneoplastic foci could be detected as GST-II-positive in the female mice, while those in males were observed as to have decreased GST-II relative to the background. Class alpha GST-I and class mu GST-III did not exhibit any remarkable changes in preneoplastic foci. This result indicates that GST-II is a useful positive and negative marker for preneoplastic lesions in female and male mouse livers. In addition, class pi GST-II may be useful for the rapid screening hepatocarcinogens in mice because GST-II-positive or -negative single cells and minifoci, considered as precursor initiated populations, were detectable in females and males at 12 weeks after the DEN injection. PMID- 8453733 TI - Effects of dietary retinoic acid on skin papilloma and carcinoma formation in female SENCAR mice. AB - Previously we have shown that dietary retinoids are essential for papilloma formation induced by either an initiation-promotion or a complete skin carcinogenesis protocol. The present study was conducted to further determine the effect of dietary retinoic acid (RA) on papilloma formation and the conversion of papillomas to carcinomas. Skin tumors were induced in 3 week old female SENCAR mice by an initiation-promotion protocol with one application of 20 micrograms of 7,12-dimethylbenz[a]anthracene (DMBA), followed by 20 weekly applications of 2 micrograms of 12-O-tetradecanoylphorbol-13-acetate (TPA). Mice were fed RA at one of the three doses: 0.3 (nutritionally marginal dose), 3 (near physiological) and 30 (pharmacological) micrograms/g of diet. Mice fed 30 micrograms of RA/g of diet had the same survival rate as the other two groups despite a lower body weight and all three groups had similar papilloma incidence, which reached 100% at age 18 weeks. Mice fed 3 micrograms of RA/g of diet had the highest papilloma yield (approximately 14 papillomas/mouse) of all groups and it peaked between weeks 18 and 38 of age. These papillomas later regressed such that mice from all three groups had about the same papilloma yield at week 44 of age. Mice fed 30 micrograms of RA/g of diet failed to develop any visible carcinoma, while mice fed 0.3 or 3 micrograms/g showed 1.9% conversion of papillomas to carcinomas. Therefore, dietary RA at 30 micrograms/g of diet inhibited the conversion of papillomas to carcinomas without affecting papilloma incidence. In addition, dietary RA at 30 and 0.3 micrograms/g of diet lowered papilloma yield. PMID- 8453734 TI - Calciotropic hormones raise the chemically detectable [Pi] in UMR 106-06 osteoblast-like cells. AB - Uptake of orthophosphate (Pi) by osteoblast-like cells is known to be stimulated by parathyroid hormone (PTH), but effects on intracellular [Pi] have not been investigated. Here we show in rat osteoblast-like cells (UMR 106-06) that PTH (10(-11) to 10(-7) M) increases both 32Pi uptake and cellular [Pi] by up to 50 per cent. 1,25 Dihydroxyvitamin D3 (1,25D) (10(-12) to 10(-6) M) and salmon calcitonin (CT) (10(-12) to 10(-6) g ml-1) also increased cellular [Pi] (by up to 60 per cent), but the percentage increases in total cellular 32Pi uptake were smaller. The effects of 1,25D were transient (observable at 80 min and 6 h but not 24 h), and were also observed with 24,25 dihydroxy- and 25 hydroxyvitamin D3. Transient degradation of organic phosphorus pools to Pi might contribute to this increased [Pi]. These pools remain to be identified but were not shown to be phospholipids. Foetal bovine serum also affected cellular [Pi]. Care is therefore needed in distinguishing direct hormonal effects on cellular [Pi] from indirect effects arising from changes in the rate of cell growth. PMID- 8453735 TI - The effects of tunicamycin on the metabolism of acetylated low density lipoproteins. AB - The effect of tunicamycin (TM) on the metabolism of acetylated low-density lipoprotein (AcLDL) was examined to determine whether N-linked glycosylation is required for the proper function of the AcLDL pathway. Proteolytic degradation of [125I]-AcLDL was increased twofold in the presence of TM. This did not occur via an increase in total lysosomal enzyme activity or extracellular proteolysis; rather, the rate of uptake of [125I]-AcLDL was increased. The enhanced degradation of AcLDL did not lead to a commensurate increase in the rate of synthesis of cholesteryl oleate. Conversely, the rate of cholesterol esterification was reduced in the presence of TM. The uptake of [125I]-AcLDL was more sensitive to inhibition by chloroquine in TM-treated cells. However, the presence of TM did not affect the ability of chloroquine to inhibit constitutive recycling of AcLDL binding sites. These results suggest that N-linked glycosylation may be involved in the regulation of AcLDL metabolism in J774 cells. PMID- 8453736 TI - Ethanol-induced inhibition of ventricular protein synthesis in vivo and the possible role of acetaldehyde. AB - We have determined the extent to which acute ethanol administration perturbs the synthesis of ventricular contractile and non-contractile proteins in vivo. Male Wistar rats were treated with a standard dose of ethanol (75 mmol kg-1 body weight; i.p.). Controls were treated with isovolumetric amounts of saline (0.15 mol l-1 NaCl). Two metabolic inhibitors of ethanol metabolism were also used namely 4-methylpyrazole (alcohol dehydrogenase inhibitor) and cyanamide (acetaldehyde dehydrogenase inhibitor) which in ethanol-dosed rats have been shown to either decrease or increase acetaldehyde formation, respectively. After 2.5 h, fractional rates of protein synthesis (i.e. the percentage of tissue protein renewed each day) were measured with a large (i.e. 'flooding') dose of L [4-3H]phenylalanine (150 mumol (100 g)-1 body weight into a lateral vein). This dose of phenylalanine effectively floods all endogenous free amino acid pools so that the specific radioactivity of the free amino acid at the site of protein synthesis (i.e. the amino acyl tRNA) is reflected by the specific radioactivity of the free amino acid in acid-soluble portions of cardiac homogenates. The results showed that ethanol alone and ethanol plus 4-methylpyrazole decreased the fractional rates of mixed, myofibrillar (contractile) and sarcoplasmic (non contractile) protein synthesis to the same extent (by approx. 25 per cent). Profound inhibition (i.e. 80 per cent) in the fractional rates of mixed, myofibrillar and sarcoplasmic protein synthesis occurred when cyanamide was used to increase acetaldehyde formation. There was also a significant decrease in cardiac DNA content. The results suggest that acute ethanol-induced cardiac injury in the rat may be mediated by both acetaldehyde and ethanol. PMID- 8453737 TI - Proliferation-associated increase in sensitivity of mammary epithelial cells to inositol-1,4,5-trisphosphate. AB - Injection of D-myo-inositol-1,4,5-trisphosphate (IP3) was found to induce a transient increase of intracellular Ca2+ concentration in cancerous mammary cells (MMT060562) and in normal mammary cells treated with epidermal growth factor. Responses to injection of either D-myo-inositol-1,4-bisphosphate (IP2) or D-myo inositol-1,3,4,5-tetrakisphosphate (IP4) were small or absent. Furthermore, normal mammary cells cultivated with low-protein serum replacement alone or in the presence of differentiation-inducing hormones (insulin + cortisol + prolactin) were less sensitive to IP3. Thapsigargin induced a transient increase of Ca2+ due to the release of Ca2+ from an intracellular pool. There was no difference in the peak heights of the thapsigargin-induced Ca2+ increase when mammary cells were cultivated in the presence or absence of epidermal growth factor or insulin + cortisol + prolactin. These findings suggest that the releasable intracellular Ca2+ pool remained unchanged whereas sensitivity to IP3 increases during the proliferation stage. Mechanical stimulus of a mammary cell induces an increase of intracellular Ca2+ in the stimulated cell. A certain stimulating factor is released from the mechanically stimulated cell into the extracellular space, and it induces an increase of Ca2+ in surrounding cells. In contrast, the IP3-induced Ca2+ increase in both cancerous and epidermal growth factor-treated normal mammary cells did not spread to adjacent cells. Therefore, increase of Ca2+ is not sufficient to account for the release of stimulating substances from mammary cells in the mechanically-induced spreading response. PMID- 8453738 TI - Abnormalities of DNA in human osteoarthritic articular cartilage. AB - The normal amount of DNA in human diploid nuclei was determined by the use of the Feulgen reaction measured by microdensitometry. The DNA-content of nuclei in normal human articular cartilage was determined in nuclei of zones 3 and 4 of cartilage of the femoral head removed from osteoporotic fractured necks of femur. Analysis of the results indicated that a degree of synthesis of DNA occurred even in these zones of very elderly persons. Results on these zones in the articular cartilage of osteoarthritic joints indicated that different populations occurred. In some there was DNA-synthesis related to tetraploidy; in others, the DNA was very stable to acid hydrolysis with no sign of biosynthetic activity; in the last group, which contained erosions of the superficial zones, the DNA was unstable to hydrolysis. PMID- 8453739 TI - Change of liver metabolism of 1,2-dibromoethane during simultaneous treatment with carbon tetrachloride. AB - The combination of carbon tetrachloride (CCl4) and 1,2-dibromoethane (DBE) in isolated rat hepatocytes led to a significant potentiation of both lipid peroxidation and of plasma membrane damage observed after a single treatment with CCl4. Such a synergistic effect appeared to be related to the CCl4-induced shift of DBE metabolism from the cytosolic conjugation with glutathione towards the microsomal transformation into toxic intermediates. In fact, CCl4 significantly inactivated hepatocyte total GSH-transferase, i.e. the DBE detoxification pathway. Furthermore, while the microsomal metabolism of CCl4 was not affected by the simultaneous presence of DBE, the amount of DBE reactive metabolites covalently bound to hepatocyte protein was significantly enhanced in the presence of CCl4. PMID- 8453740 TI - Plasma catecholamine levels in porcine Escherichia coli septicaemia and following treatment with buprenorphine or naloxone. AB - Changes in plasma catecholamine levels in response to the induction of shock and following treatment with buprenorphine or naloxone were determined in a porcine model of Escherichia coli septicaemia. Thirty animals were anaesthetised with alpha-chloralose and infused with live E. coli over 2 hr. One hour after starting the infusion, cardiac index, mean arterial pressure, and pH had decreased significantly (P < 0.001), and there was a significant increase in mixed venous blood lactate concentrations (P < 0.001). This was associated with significant increases in plasma concentrations of adrenaline and noradrenaline (P < 0.001). There was a strong correlation between the extent of the increase in circulating catecholamines and the severity of shock (as reflected by haemodynamic changes and lactic acidosis) as well as significantly higher peak plasma catecholamine concentrations (P < 0.01) and dramatic terminal increases in circulating catecholamines in nonsurviving animals. Animals were randomly divided into three groups and received either naloxone or buprenorphine or an equivalent volume of normal saline and were monitored for a further 3 hr. Both naloxone and buprenorphine produced significant improvements in cardiac index (P < 0.05) and limited the development of acidosis (P < 0.05). This was not associated with any further increase in plasma catecholamine concentrations; indeed, catecholamine levels tended to decrease in treated animals but continued to increase in controls. In summary, we have shown a correlation between the increase in plasma catecholamines and the severity of shock in this model. In addition, we observed that the beneficial effects of treatment with buprenorphine or naloxone were not accompanied by any further increase in plasma catecholamine concentrations. PMID- 8453741 TI - Effects of coenzyme Q10 on the mediator cascade of sepsis. AB - Coenzyme Q10 (CoQ) has been promoted as an effective agent for reducing the deleterious effects of septic shock by acting as an oxygen free radical scavenger and thus stabilizing mitochondrial membranes and by inhibiting the arachidonic acid metabolic pathway and the formation of various prostaglandins. This study was undertaken to evaluate the effect of CoQ in a live Escherichia coli model of canine septic shock. Group I (E. coli, n = 5) animals received an LD100 dose of 10(9) live E. coli/kg and were given no further treatment. Group II (CoQ, n = 5) animals received a 20-mg/kg bolus of CoQ without further treatment. Group III (CoQ + E. coli, n = 5) animals received a 20-mg/kg bolus of CoQ 10 min prior to a bacterial infusion as in group 1. Mean arterial pressure stabilized at 70% of baseline levels (P < .002), while cardiac output remained near 50% of baseline levels (P < .053) in group III compared to group I dogs. The arachidonic acid metabolites, prostaglandin E2, Thromboxane B2, and leukotriene B4 were significantly elevated in groups I and III (vs. group II) (P < 0.05). The catecholamines, tumor necrosis factor (TNF) and interleukin 6 (IL-6) were significantly elevated in groups I and III (vs. group II) (P < 0.05). Fluorescent products (lipid peroxidation activity) were elevated in group I (vs. groups II and III) at 120 and 180 min (P < 0.05). We conclude that CoQ supports cardiovascular hemodynamics and prevents free radical mediated lipid peroxidation during live E. coli septic shock, and its effect is not due to altered levels of humoral or cytokine mediators. PMID- 8453742 TI - Role of sympathetic nervous system in hypotension induced by platelet-activating factor in anesthetized dogs. AB - This experiment was designed to investigate whether platelet-activating factor (PAF)-induced hypotension in anesthetized dogs produces changes in sympathetic activity in the heart, kidney, liver, and adrenal gland in intact animals (n = 5) and in animals with complete systemic baroreceptor denervation (n = 5). Following intravenous injection of PAF (10 micrograms/kg) in animals with intact baroreceptors, systemic blood pressure fell significantly. However, sympathetic nerve activity in the kidney, liver, and adrenal gland revealed a biphasic pattern: an initial increase (within 30 sec) followed by a progressive reduction below the preinjection level. In contrast to these nerve responses to PAF, only cardiac nerve activity showed an initial and significant increase, and it remained elevated above the preinjection level until the end of the experiment (10 min). In animals with complete systemic baroreceptor denervation, these sympathetic responses to PAF did not differ significantly from the responses in the intact animals. These results indicate that intravenous injection of PAF produces differential control of sympathetic nerve activity in different organs. The contribution of systemic baroreceptors to reflex compensations is minor in PAF-induced hypotension. PMID- 8453743 TI - Comparison of the induction of endotoxin tolerance in endotoxemia and peritonitis by monophosphoryl lipid A and lipopolysaccharide. AB - We compared the induction of endotoxin tolerance with Salmonella minnesota monophosphoryl lipid A (MPL), a nontoxic derivative of lipid A, and S. minnesota endotoxin (LPS) in lethal endotoxemia and peritonitis. Lethal endotoxemia was induced by injecting 750 micrograms/mouse LPS intravenously. Cecal ligation and perforation was used to induce peritonitis. Tumor necrosis factor (TNF) was measured by immunoassay at 2 hr after lethal endotoxin infusion and 24 hr after peritonitis. A dose of 0.1 micrograms/mouse of MPL or LPS significantly reduced endotoxin mortality from 100% to 50% and 27%, respectively (P < 0.05). The LD50 for a 0.1 micrograms dose of MPL was 750 micrograms of LPS and the LD50 for a 0.1 micrograms dose of LPS was 1150 micrograms of endotoxin (P < 0.05). TNF levels decreased linearly when increasing doses of MPL and LPS were used to induce tolerance. At higher pretreatment doses of LPS, survival benefits were attenuated despite the reduction in TNF levels. A 25 micrograms dose of LPS reduced mortality from peritonitis from 93% to 45% (P < 0.05). Although MPL reduced short term mortality, overall mortality was not significantly reduced despite using large doses of MPL. TNF levels peaked at 24 hr and were significantly lower than those following lethal endotoxemia. The induction of endotoxin tolerance by LPS and MPL is dose dependent, and LPS is modestly more effective in inducing endotoxin tolerance than MPL. Both LPS and MPL are significantly less effective in protecting against lethality from peritonitis. PMID- 8453744 TI - Dopexamine hydrochloride maintains portal blood flow and attenuates hepatic ultrastructural changes in a porcine peritonitis model of multiple system organ failure. AB - Fifteen anesthetised pigs (25-30 kg) were divided into three equal groups, sham, dopexamine (D) (10 micrograms/kg/min), and placebo (P). Sepsis was induced by fecal peritonitis in the D and P groups and colloid was infused to try to maintain mean arterial blood pressure (MABP) at a constant value and the hemodynamics measured at baseline and hourly for 8 hr. There was an initial increase in MABP and systemic vascular resistance (SVR) in the P group but not the dopexamine (D) group. Cardiac output (CO) in the P group showed a small decline but increased in the D group. The portal blood flow (PVF) in the P group fell with MABP but increased in the D group as MABP fell. The sham group showed normal ultrastructure and cellular integrity. Occlusion of the hepatic sinusoids was similar in the D and P groups. There was a greater area of Kupffer cells and endothelial cells in the P group, suggesting a greater inflammatory reaction than was found in the D group. Ultrastructure and mitochondrial integrity was better maintained in the D group. Dopexamine hydrochloride infusion maintained CO, increased PVF, and attenuated hepatic ultrastructural changes compared to placebo in a porcine fecal peritonitis model of multisystem organ failure. PMID- 8453745 TI - Enhancement of urine output and glomerular filtration in acutely oliguric patients using low-dose norepinephrine. AB - A prospective clinical trial was initiated to test the hypothesis that low-dose norepinephrine enhances urine output and renal function in oliguric surgical patients. Norepinephrine (0.05 or 0.1 micrograms/kg/min) was infused into nine oliguric (< or = 0.5 ml/kg/hr), volume-replete, hemodynamically stable patients. There was an average increase of urine output of 13 ml/hr (48% over baseline) and an increase of 31.7 ml/min (47% over baseline) in creatinine clearance. Both these results were statistically significant. Mean arterial pressure was the only hemodynamic parameter that changed significantly, rising an average of 12 mm Hg. We conclude that low-dose norepinephrine infusion may enhance renal function and urine output in acutely oliguric surgical patients who have been appropriately fluid resuscitated. PMID- 8453746 TI - Regulation of glucose metabolism after endotoxin and during infection is largely independent of endogenous tumor necrosis factor. AB - Increased hepatic glucose production and glucose utilization involving multiple tissues occur in response to administration of bacterial lipopolysaccharide (LPS) and are metabolic hallmarks of hypermetabolic sepsis. As a proximal mediator in the host response to infection-like challenges, tumor necrosis factor (TNF) may enhance glucose metabolism by directly interacting with cells or by initiating a cascade of events leading to changes in glucose production and utilization. To determine if endogenous TNF is an important mediator in LPS- or sepsis-induced changes in glucose metabolism, rats were pretreated with a neutralizing goat anti TNF IgG antibody prior to intravenous LPS or subcutaneous live Escherichia coli administration. Whereas high levels of plasma TNF were observed in rats not pretreated with anti-TNF, TNF was not detected 90 min after LPS in rats receiving the antibody. Pretreatment with anti-TNF attenuated the increase in plasma lactate and glucagon levels in LPS-challenged rats but failed to ameliorate the LPS-induced hyperglycemia and increase in glucose rate of appearance (Ra). The LPS-stimulated increase of in vivo glucose metabolic rate (Rg) of examined tissues, measured with [14C]-2-deoxyglucose, was not altered by anti-TNF. Likewise, rats treated with anti-TNF prior to induction of hypermetabolic infection exhibited usual increases in whole-body glucose Ra and metabolic clearance rate. Although neutralizing TNF failed to prevent the sepsis-induced augmentation of Rg in any tissue examined, it reduced the increase in the lung (P < 0.05) and tended to decrease it in other barrier tissues as well as in the spleen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8453747 TI - Naloxone potentiates inotropic but not chronotropic effects of isoproterenol in vitro. AB - Tachycardia often limits the usefulness of conventional beta-adrenergic inotropic therapy; therefore, a compound possessing positive inotropic but not chronotropic properties would be useful. These experiments determined the inotropic and chronotropic properties of naloxone in spontaneously contracting guinea pig atria and electrically paced papillary muscles in the presence and absence of isoproterenol. In atria naloxone exhibited no significant intrinsic inotropic properties. In the presence of isoproterenol, naloxone increased contractility in spontaneously contracting atria and electrically paced ventricular tissues by 11% and 79% respectively, without any significant change in contraction rate. Since naloxone potentiated the inotropic but not chronotropic effects of isoproterenol, it may be a useful adjunct to conventional beta-adrenergic therapy where an inotropic but not chronotropic effect is desired. PMID- 8453748 TI - Diltiazem reduces whole blood viscosity following trauma-hemorrhagic shock and resuscitation. AB - Although diltiazem improves function in several organs following trauma hemorrhagic shock, the mechanism remains unknown. It is hypothesized that diltiazem maintains red blood cell calcium-to-magnesium ratio, resulting in better deformability of red blood cells. This should reduce blood viscosity, allowing red blood cells to traverse the microcirculation more efficiently and improve tissue oxygenation. To study this, rats (n = 23) underwent cannulation of various blood vessels and were divided into five groups: Group 1, control rats which had surgery only; Group 2, sham-operated rats which were not hemorrhaged but were infused with a volume of lactated Ringer's solution (LRS) equivalent to that given to the hemorrhaged animals (Groups 4 and 5); Group 3, hemodilution animals which were maintained at normal blood pressure but with the hematocrit lowered to values equivalent to hemorrhaged rats (Groups 4 and 5); Groups 4 and 5, animals which underwent fixed pressure (40 mm Hg) hemorrhage, followed by resuscitation with LRS, 5x the shed blood volume, and were given IV saline (Group 4) or 400 micrograms diltiazem/kg (Group 5) with the resuscitation. Blood viscosity was measured at the end of resuscitation with a Brookfield DV-III viscometer. Results showed that blood viscosity was markedly reduced in the diltiazem treatment group, but was unchanged in any of the other groups versus the control. Thus, the beneficial effects of diltiazem after trauma-hemorrhage and resuscitation may be due in part to the marked decrease in blood viscosity allowing for improved oxygen delivery and removal of metabolites. PMID- 8453749 TI - It was the best of times, it was the worst of times. PMID- 8453750 TI - Complications and symptoms in disposable extended wear lenses compared with conventional soft daily wear and soft extended wear lenses. AB - We conducted a historical cohort study of 2,433 cosmetic contact lens wearers (1,055 conventional [non-disposable] daily wear lens users, 905 disposable extended wear lens users, and 473 conventional extended wear lens users) in order to estimate the rates of occurrence of complications and symptoms among disposable extended wear contact lens users and compare these rates with those for conventional soft daily wear users and conventional soft extended wear users. Data were abstracted from the office records of eight eye care practitioners for the period February 1987 through April 1989. The prevalence of all complications for disposable extended wear lens users was not significantly different from the prevalence for conventional daily wear lens users but was significantly lower than the prevalence for conventional extended wear lens users. The incidence of ulcers among disposable extended wear lens users did not differ significantly from the incidence found with conventional extended wear, but was significantly higher than the rate for conventional daily wear. Disposable extended wear lenses, in contrast to conventional extended wear lenses, may be more strongly associated with benign peripheral infiltrates than with the more serious central ulcers. Disposable extended wear lens users reported symptoms less frequently at routine scheduled visits than both conventional daily wear and conventional extended wear users and had a lower rate of unscheduled visits for complications and symptoms. PMID- 8453751 TI - Corneal topography for rigid gas permeable lens fitting after penetrating keratoplasty. AB - Computerized videokeratography may facilitate rigid gas permeable (RGP) contact lens fitting in post-penetrating keratoplasty (post-PK) eyes. We used the EyeSys Corneal Analysis System to create topographic maps of 19 post-PK eyes from October 1990 to April 1991. An initial trial lens was selected based on the average keratometric value from two separate topographic color maps. A standard protocol was used to select the initial trial lens on the basis of computer generated topographic keratometry readings. Final lens selection was based on clinical performance. A comparison of the base curve of the initial contact lens selected using computerized videokeratography and the base curve that would have been selected by standard keratometry showed a statistically significant difference (P = 0.02). Three month follow-up data were also evaluated. There was no statistically significant difference between the base curve of the initially dispensed contact lens and the base curve of the lens worn after 3 months. However, modifications in the fit were made in 9 of 19 patients. Two patients were RGP contact lens failures and were refit with SoftPerm lenses. PMID- 8453752 TI - The efficacy of hydrophilic contact lens cleaning systems in removing protein deposits. AB - New, never-worn, individual hydrophilic contact lenses were incubated in an artificial tear solution (containing lysozyme, albumin, lactoferrin, and glycoprotein) for 24 hours at 37 degrees C with constant stirring. These lenses were then cleaned following the manufacturer's instructions with one of six commercial cleaning systems: AOSEPT, CONSEPT, Oxysept, ReNu, Opti-Free and thermal disinfection in conjunction with the Allergan Enzymatic Contact Lens Cleaner. The protein remaining on each lens after cleaning was removed and then quantified by the Bio-Rad Protein Assay. High resolution gel electrophoresis was used to assess the individual protein profile patterns. We found that only one third to one-half of the protein deposited on a lens is removed by the above cleaning systems. Of the proteins in the artificial tear solution only lysozyme is removed by cleaning, while lactoferrin, albumin, and glycoprotein tend to remain on the lens. Since many of the complications experienced by contact lens wearers are thought to be related to protein deposits on their lenses, our results suggest the need for more effective contact lens cleaning solutions. PMID- 8453753 TI - Efficacy of a one-step hydrogen peroxide system for disinfection of soft contact lenses. AB - We investigated the efficacy of a one-step hydrogen peroxide system by culturing soft contact lenses before and after exposure to the AOSEPT disinfection system. Sixteen of 38 soft contact lenses obtained from asymptomatic wearers showed microbial growth. Nine cultures were positive for Pseudomonas sp., four showed growth of Staphylococcus sp., two were positive for beta-hemolytic streptococci, and one culture was positive for Alcaligenes faecalis. A second culture of the contact lenses after hydrogen peroxide disinfection showed no growth in 12 of the 16 previous positive cultures. The rate of disinfection was 55% for Pseudomonas sp. and 100% for other bacteria. PMID- 8453754 TI - A new in vitro method for assessing the potential toxicity of soft contact lens care solutions. AB - We describe a method for determining the cytotoxic effect of soft contact lens care solutions. The method provides a means for the direct exposure of mammalian cells to solutions and to lenses that have been soaked in solutions. Cytotoxicity was indicated by significant increases in the number of dead cells relative to controls. The cytotoxicity of a test battery of eight compounds was determined, particularly benzalkonium chloride (BAK). In addition, nine commercial soft contact lens care products containing a variety of preserving/disinfecting agents were also examined. A modification of the basic assay for assessing the kinetics of toxicity is also described. The results indicate that this new method is useful for identifying compounds that bind to soft contact lenses, such as BAK, and induce cytotoxicity and others that should be rinsed from lenses or neutralized (such as hydrogen peroxide) to minimize the potential for irritation. PMID- 8453755 TI - A comparison of the TMS-1 and the corneal analysis system for the evaluation of abnormal corneas. AB - We used two computerized corneal topography instruments (EyeSys Laboratories' Corneal Analysis System and the Topographic Modeling System (TMS-1) from Computed Anatomy, Inc.] to evaluate 18 eyes (ten patients) with abnormal corneas. The diagnoses included keratoconus, corneal scars, and residual postoperative astigmatism following refractive surgery. The patients were randomly selected from a busy corneal practice to include those with significant corneal refractive error whose management, it was believed, would benefit from corneal topography imaging. Images were taken with both systems, and comparisons were made of the ease of operation, the accuracy of corneal readings, and the usefulness of generated data. Three millimeter zone (Corneal Analysis System) and Simulated Keratometry (TMS-1) values were also compared to each other and to standard keratometric readings. We found the two systems to be very similar in their application and results, although certain differences were apparent in terms of operation, patient acceptance, and the ability to obtain useful data from the more distorted corneas. Neither system worked ideally for severely irregular surfaces. PMID- 8453756 TI - Accuracy of the PAR corneal topography system with spatial misalignment. AB - The PAR Corneal Topography System is a computerized corneal imaging system which uses close-range raster photogrammetry to measure and produce a topographic map of the corneal surface. Raster photogrammetry is a standard method of extracting object information by projecting a known pattern onto an object and recording the distortion when viewed from an oblique angle. Unlike placido disc based videokeratoscopes, the PAR system requires neither a smooth reflective surface nor precise spatial alignment for accurate imaging. We studied both the accuracy of the system with purposeful misalignment (defocusing) of the test object and determined the ability to image freshly deepithelialized, keratectomized, and photoablated corneas. The PAR system was both accurate and reproducible in imaging calibrated spheres within a defined zone in space. Whole cadaver eyes were imaged both before and immediately after removal of the epithelium, lamellar keratectomy, and laser photoablation. The system demonstrated the ability to image irregular, deepithelialized, and keratectomized corneas. The ability to maintain accuracy without precise alignment and the facility to image freshly deepithelialized and keratectomized corneas may make the system suitable for intraoperative refractive monitoring. PMID- 8453757 TI - Corneal refraction and topography in school myopia. AB - Changes in corneal refraction and topography among 145 myopic children were monitored over a three-year period as part of a clinical trial of myopia treatment. The spherical equivalent of the right eye increased from -1.46 D to 3.13 D. Refractive astigmatism increased from 0.28 D to 0.46. Corneal astigmatism, horizontal and vertical corneal curvatures, as well as shape factors, did not change significantly. The mean deviation of the corneal apex from the visual axis increased from 0.48 mm to 0.67 mm. Girls showed steeper corneal curvatures than boys. For both sexes the vertical corneal curvatures were steeper, and shape factors were smaller than those along the horizontal plane. Axial elongation of the eye was the primary explanation for myopic progression. PMID- 8453758 TI - Conrad Berens Lecture. Corneal ulcers related to contact lenses. PMID- 8453759 TI - Corneal ulcers and disposable extended wear lenses. PMID- 8453760 TI - Developmental transition by spinal cord plasma membranes of embryonic chick from permissive to restrictive substrates for the morphological differentiation of neuroblastoma x glioma hybrid NG108-15 cell. AB - Recent studies of spinal cord development and plasticity, in chick, have demonstrated a loss of regenerative ability correlating to embryonic day (E) 13 of the 21-day developmental period. Here we describe membrane fractions from embryonic chick spinal cords as permissive or restrictive substrates for the neuron-like differentiation of neuroblastoma x glioma hybrid NG108-15 cells, in vitro. Plasma membranes were purified from the thoracic spinal cord of embryos at a series of developmental stages (E10-E18). Micro-well plates were coated with the fractions and NG108-15 cells cultured thereon. Cells adhered to the E10 coated wells and began to differentiate after 2 h, becoming highly differentiated, with neurites 2-3 times longer than the diameter of the cell body after 24 h in in culture. In contrast, cells cultured in E18-coated wells remained as clusters of undifferentiated cells of rounded morphology, even after 48 h in culture. As well, the permissive and restrictive plasma membranes were assessed semiquantitatively as the number of adhering cells after 20 h of culture. Adhesion of cells to the substrate decreased as the embryonic age of the plasma membrane substrate increased. Examination of the plasma membrane fractions, using SDS-PAGE, revealed several proteins in the 40-60 kDa range that varied substantially between E12, E14 and E18. Results of this study provide in vitro confirmation of previous in vivo findings; namely, that early embryonic spinal cord is initially permissive for neuritic outgrowth becoming restrictive around E13.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8453761 TI - The innervation of calcitonin gene-related peptide to the Purkinje cells and granule cells in the developing mouse cerebellum. AB - The present study analyzed the ontogeny of calcitonin gene-related peptide-like immunoreactive (CGRP-IR) structures in the mouse cerebellum. No CGRP-IR neurons were detected at any stage, but three types of CGRP-IR fibers were seen: (1) CGRP IR dense fiber plexuses which appeared transiently in the developing cerebellum, (2) thin varicose fibers, and (3) mossy fiber-like fibers. The CGRP-IR dense fiber plexuses appeared in the developing Purkinje cell layer at postnatal day 2. From postnatal days 6 to 11, these fibers formed pericellular nests around Purkinje cells. After that stage, these fibers rapidly disappeared and no such plexuses were seen in the adult cerebellum. CGRP-IR fiber plexuses were not evenly distributed, and they had a parasagittal banded pattern in the frontal sections. These plexuses existed in the region of all vermis, crus 1 of the ansiform lobe, simplex lobule, and flocculus, while the other lobules were devoid of such fibers. Under electron microscopy, these CGRP-IR fibers were seen to make synaptic contacts with somatic spines of Purkinje cells, suggesting that CGRP-IR plexuses were closely related to the developing Purkinje cells. Mossy fiber-like CGRP-IR fibers appeared in the granular layer on postnatal day 2, and increased in number to reach a peak on postnatal day 12. Thereafter, they decreased slightly to reach a plateau on postnatal day 30. Under electron microscopy these CGRP-IR fibers were revealed to be the mossy fibers which regulated the granule cells. Thin varicose CGRP-IR fibers were rarely seen at birth, but on postnatal day 8, many fibers appeared in all layers and increased by postnatal day 30. They distributed equally throughout the cerebellar cortex with a slight predominance in density in the molecular and Purkinje cell layer. Immunoelectron microscopic analysis showed that these fibers made synaptic contacts with small dendrites in the molecular layer. PMID- 8453762 TI - Expression of members of the trk family in the developing postnatal rat brain. AB - Tyrosine protein kinases trk, trkB and trkC are essential components of the high affinity receptors necessary to mediate biological effects of the neurotrophins NGF, BDNF, NT-3 and NT-4. Here we report on the expression of these receptors during postnatal development in the rat brain. Cells expressing mRNAs encoding different members of the trk family were identified by in situ hybridization using oligonucleotides complementary to their respective mRNA. In septum, striatum and brainstem, higher levels of trk mRNA were detected at 2 and 4 weeks than at 1 weeks of age. In thalamic nuclei associated with the limbic system, trkB and trkC mRNA were highly expressed at P1 to P7, but the expression declined gradually in 2 and 4 week old animals. Other structures where a developmentally regulated expression was seen included the tenia tecta and piriform cortex where trkB mRNA was not detected until 2 weeks of age. A high labeling was found for trkC mRNA in the deeper parts of neocortex in P1 and P4 animals, while in 2 and 4 weeks old animals the highest labeling was seen over the outer neocortical layers. Several brainstem nuclei showed a higher labeling for trkC mRNA at P1 to P7 than in animals of older age. These data show that expression of members of the trk family is developmentally regulated during postnatal brain development and suggest that high affinity neurotrophin receptors mediate a transient response to neurotrophins in many regions during brain ontogeny. PMID- 8453763 TI - Developmentally regulated expression of pleiotrophin, a novel heparin binding growth factor, in the nervous system of the rat. AB - Pleiotrophin (PTN) is a newly identified heparin-binding growth factor which is closely related to the retinoic acid-inducible MK protein. PTN is expressed at high levels in perinatal brain and promotes neurite outgrowth from embryonic brain neurons and mitogenesis in fibroblasts, suggesting that it may play an important role in the development of the nervous system. We have used in situ hybridization to examine PTN expression in the developing and adult rat nervous systems. During embryogenesis, PTN mRNA is primarily expressed by neuroglial progenitor cells in the subependymal layer of the central nervous system (CNS), whereas during the perinatal period high levels of PTN transcripts are found in neurons as well as glial elements (astrocytes and oligodendrocytes). In the adult brain, PTN expression is markedly decreased relative to early postnatal brain and, in contrast to the neuronal and glial expression observed in young animals, is confined to specific neuronal subpopulations (especially hippocampal CA1-3 regions, cerebral cortex laminae II-IV). PTN is also expressed in the developing spinal cord and eye. In the peripheral nervous system (PNS), PTN mRNA is present in ganglionic neurons during embryogenesis. In adult ganglia, however, PTN expression becomes localized to the satellite cells of the ganglia. The developmental pattern of PTN expression in the CNS and the 'switch' in expression from neurons to satellite cells in the PNS suggests that it has important functions not only in the developing nervous system, but also in the adult CNS and PNS and that the functions performed by this growth factor change during ontogeny. We have also found that levels of PTN mRNA are dramatically but transiently elevated in neurons of the hippocampus, piriform cortex and parietal cortex following a chemically induced seizure, indicating that neuronal PTN mRNA expression is increased by intense physiological stimuli and may play a role in the response to these stimuli. PMID- 8453764 TI - Ontogeny of the erythroid/HepG2-type glucose transporter (GLUT-1) in the rat nervous system. AB - Central nervous system (CNS) microvessels of adult mammals have an unusually high density of the facilitative glucose transporter GLUT-1. Most systemic microvessels and those of the brain's circumventricular organs, which lack 'barrier' properties, do not express a high density of GLUT-1. Thus, a high GLUT 1 density is a marker of adult brain endothelium. To determine the stage at which CNS microvessels acquire GLUT-1, we studied by immunocytochemistry GLUT-1 ontogeny in the rat CNS from embryonic day (E) 11 to senescence. At E11, before blood vessels invaded the neuroectodermal tube, GLUT-1 immunoreactivity was already evident in the perineural plexus of vessels and in most of the vascular endothelium of the embryo. GLUT-1 immunoreactivity was also evident in the neuroectoderm. The neuroectoderm gradually lost GLUT-1 expression, and at about E16, GLUT-1 immunoreactivity was no longer detectable in most of the neuroectodermal epithelium, while CNS microvessels had increased their GLUT-1 immunoreactivity. By birth, GLUT-1 immunoreactivity in the CNS was restricted to the endothelium, the epithelium (but not the endothelium) of the choroid plexus, and tanycytes. This cellular distribution of GLUT-1 did not change much between birth and senescence despite considerable postnatal brain development and the increased brain capillary density. Our results suggest that while a CNS factor(s) may not have a role in the induction of the high expression of GLUT-1 in CNS endothelium, such a factor(s) is probably important in maintaining the high level of GLUT-1 in these endothelia. PMID- 8453765 TI - The prenatal development of the anterior commissure in hamsters: pioneer fibers lead the way. AB - The prenatal development of the anterior commissure (AC) was studied in 130 hamster embryos with ages varying from E12 to E16 (E1 = day of conception and E16 = P1 = day of birth) by use of carbocyanine crystals (DiI, DiA and/or DiO) implanted into different rostrocaudal segments of the paleocortex. On E12 and E13, many AC axons were seen with tortuous trajectories pointing towards the midline (precrossing stage). On E13.5 and E14, most AC fibers abutted the midsagittal plane, led by a few pioneer axons that grew as far as 500 microns ahead into the opposite hemisphere (crossing stage). Pioneers were present in most brains at these ages irrespective of the rostrocaudal position of the carbocyanine crystal. Somata of pioneer axons could be identified by retrograde labelling. They were characteristically immature neurons, located either in the olfactory peduncle or in the superficial layers of the olfactory cortex. On E14.5 and E15, pioneers and followers were seen close to the targets and on E15.5 and E16 interstitial budding occurred, and arborization started within the olfactory peduncle and the paleocortex (postcrossing stage). If the existence of pioneer fibers represents something more than a stochastic phenomenon, their appearance in the developing AC may reflect the operation of signals at the midline and/or in the contralateral hemisphere that either accelerate the growth of pioneers, or decelerate the growth of followers. PMID- 8453766 TI - Ethanol enhances neurite outgrowth in primary cultures of rat cerebellar macroneurons. AB - Effects of ethanol on neurite outgrowth and morphometry were investigated in primary cultures of rat cerebella. Cell cultures were prepared from cerebella on embryonic day 17 (E17) for treatment with a series of ethanol concentrations (50, 75, 100, 150 and 200 mM). Ethanol did not reduce neuronal survival or attachment to the substrate at any of the concentrations that were used. Treatment with 75 mM ethanol significantly enhanced neurite outgrowth. Measurements from dissociated cultures exposed to 75 mM ethanol immediately after plating showed a significant increase in the percentage of neurite-bearing cells after 8 and 24 h in vitro. Measurements of the area and perimeter of neuronal cell bodies in dissociated cell cultures showed that the cell bodies of ethanol-treated neurons were also larger than those of control neurons. Ethanol was also associated with significant increases in the total neuritic length per cell and in the length of the longest neurite in each cell. The mean number of neurite branches was also greater in the ethanol-treated neurons. Measurements from suspension cell cultures, in which dissociated cells were suspended overnight in the presence of 75 mM ethanol prior to plating, corroborated these results. These findings suggest that ethanol may have distinct effects on neurite initiation and outgrowth and branching. The cellular mechanisms involved and the functional significance of these effects are currently not known. The present results also indicated that high concentrations of ethanol (150-200 mM) and long periods of exposure (4-7 days) were required to produce toxic effects on neurons and glial cells in this system. PMID- 8453767 TI - Transient cortical astrogliosis induced by alcohol exposure during the neonatal brain growth spurt in rats. AB - The astrocyte response to central nervous system injury induced by neonatal alcohol exposure was evaluated using radioimmunoassay and immunocytochemistry of glial fibrillary acidic protein (GFAP). Rat pups were exposed to alcohol on postnatal days 4 through 9 via artificial rearing. Alcohol solutions were administered as one of the following treatments: 10.2% (v/v) in two feedings (4.5 g/kg/day), 5.1% (v/v) in four feedings (4.5 g/kg/day), or 2.5% (v/v) in 12 feedings (6.6 g/kg/day), producing mean blood alcohol concentrations (BACs) of approximately 300, 180, and 50 mg/dl, respectively. Littermates were included as gastrostomy controls (GC) and suckle controls (SC). On postnatal day 10, GFAP concentration increased as a function of BAC, and the 10.2% alcohol treatment significantly and dramatically increased GFAP in the cortex (325% of SC). GFAP immunocytochemistry revealed frequent loci of heavily labeled reactive astrocytes surrounding small cortical blood vessels in the 10.2% group. In addition, a generalized increase in GFAP immunoreactivity was present in the deep layers of the cortex in all alcohol groups, marked by astrocytic fibrillary hypertrophy and increased density. Three-dimensional counts in layer V of parietal cortex using confocal microscopy indicated that the density of GFAP-labeled astrocytes of the 10.2% group was twice that of controls. The layer V gliosis was observable even at low BACs, while gliosis around the vasculature occurred only with high BACs. By postnatal day 15, the astroglial effects were no longer evident. These transient astroglial reactions likely constitute an important aspect of cortical pathophysiology resulting from binge alcohol exposure during the brain growth spurt of the third trimester equivalent. PMID- 8453768 TI - Characterization of the neural crest defect in Splotch (Sp1H) mutant mice using a lacZ transgene. AB - We have reinvestigated the neural crest defect of Splotch (Sp1H) mutant embryos using the tissue specific expression of lacZ by the HCMV-IEP-lacZ (CMZ) transgene as a marker. The CMZ transgene was backcrossed onto the Sp1H mutant background, which has been shown to carry mutations in the Pax-3 gene. The CMZ transgene has previously been shown to be expressed in some neural crest-derived neural tissues of midgestation embryos. The pattern of CMZ expression in Splotch mutants is not caused by alterations of transgene transcription, but demonstrates morphological deviations of neural crest development. The gradual size reduction of spinal ganglia along a rostrocaudal gradient is shown to occur concomitantly with a size reduction of the sympathetic ganglia. CMZ expression also reveals the total absence of sympathetic ganglion cells in thoracic and lumbar segments of Sp1H homozygotes, which is confirmed in serial sections. Observations in whole mounts of CMZ transgenic homozygotes suggest that cranial nerve ganglia develop normally in these embryos. CMZ is expressed in epithelial cells around the neural tube defect in Splotch mutants at the epidermal/neuroepithelial boundary. It is proposed that this expression represents premigratory neural crest cells that remain within the epithelial layer around the neural tube defect. These observations are discussed with reference to the normal pattern of Pax-3 expression. PMID- 8453769 TI - A methodological approach to superoxide dismutase (SOD) activity assay based on inhibition of nitroblue tetrazolium (NBT) reduction. PMID- 8453770 TI - Activity of phospholipase A in serum from patients with cystic fibrosis. PMID- 8453771 TI - Basal concentration of the isoenzyme BB of the glycogen phosphorylase b in human blood. PMID- 8453772 TI - Impact of circadian rhythms on the interpretation of stat measurements. PMID- 8453773 TI - The role of lipids in the increased mortality following bereavement. PMID- 8453774 TI - Selective and sensitive determination of urinary total proline and hydroxyproline by gas chromatography with flame photometric detection. AB - A selective and sensitive method for the determination of total urinary proline (Pro) and hydroxyproline (Hyp) by gas chromatography (GC) was developed. After acid hydrolysis of urine, primary amino compounds were eliminated by reaction with o-phthaldialdehyde. Subsequently, Pro and Hyp were converted into their N dimethylthiophosphoryl methyl ester derivatives and then determined by GC with flame photometric detection using a DB-5 capillary column. The derivatives were volatile and stable, giving single and symmetrical peaks. The detection limits for Pro and Hyp were 0.1 and 0.2 pmol injected, respectively. 3,4-Dehydroproline was used as an internal standard. The calibration curves for Pro and Hyp in the range 0.4-10 nmol were linear and sufficiently reproducible for quantitative determination. Overall recoveries of Pro and Hyp added to urine samples ranged from 93% to 103%. By using this method, Pro and Hyp in a small urine sample could be accurately and precisely determined without any influence from other constituent substances. PMID- 8453775 TI - A rapid GLC method for the direct analysis of plasma medium chain fatty acids. AB - A new, rapid, gas-liquid-chromatographic (GLC) method for the direct determination of plasma medium-chain fatty acids (MCFA) (from C8 to C12) which does not require derivatization procedures is described. Analysis of underivatized MCFA by GLC showed a detection limit ranging from 0.50 to 0.217 microgram depending on chain length: the longer the chain, the higher the detection limit. Compared with the HPLC and GLC methods currently described in the literature, this GLC procedure appears to be easy, adequately sensitive, accurate and well reproducible for those MCFA, like n-octanoic and n-decanoic acids, present in plasma after p.o. or i.v. MCT administration and it requires a short time (about 30 min) for complete processing. PMID- 8453776 TI - A clinical evaluation of a direct radioimmunoassay of testosterone. AB - We report the evaluation of a commercial coated tube kit (Medgenix) to the measurement of testosterone in plasma/serum samples. The accuracy, precision, specificity and recovery of the assay and the affinity of antibody for ligand were established. The range of concentrations of testosterone providing satisfactory analyses was 0.48-48 nmol/l, which is appropriate for general clinical use. Results of analysis of male and female samples obtained from the routine hospital laboratory in endocrinologically-defined groups were also reviewed. In all groups of male subjects and in normal females, the kit provided results in close agreement to those of an extraction method. With samples from women with various reproductive disorders, as well as with some samples obtained from external quality controls, the kit showed a small but significant negative bias relative to the results of the extraction method. There was, however, no evidence of bias with samples from a separate group of volunteer women with the polycystic ovary syndrome. No interference due to SHBG was detected. Clinical sensitivities using the kit were equivalent to those obtained using the extraction RIA. There was no evidence of spuriously high results in samples from females which has been a common problem with direct radioimmunoassay of testosterone. PMID- 8453777 TI - Lipoprotein(a) in diabetes mellitus. AB - Epidemiologic studies have identified lipoprotein(a) (Lp(a)) as an independent risk factor for atherosclerosis, mainly for coronary heart disease. Atherosclerosis is the most common cause of death in diabetic patients, but there is little information available concerning the importance of Lp(a) in these patients. We compared the presence or absence of late diabetic complications with Lp(a) serum concentrations in 224 patients (82 IDDM, 142 NIDDM). Lp(a) distribution was skewed as described for non-diabetic patients. Despite highly significant differences for total cholesterol, total triglycerides, HDL cholesterol, VLDL-cholesterol and VLDL-triglycerides (P < 0.001) and for LDL cholesterol (P < 0.01) Lp(a) concentrations were similar in NIDDM and IDDM (mean: 27 vs. 30, median: 12 vs. 21 mg/dl, P = 0.10). Diabetic polyneuropathy, autonomic neuropathy, nephropathy, peripheral occlusive disease, diabetic gangrene and coronary heart disease were not associated with raised Lp(a) values. Non-insulin dependent patients with retinopathy exhibited higher Lp(a) concentrations in serum than those without this complication. This significant association was lost when duration of diabetes was taken into account by logistic regression. We conclude, that other risk factors surpass the significance of Lp(a) in diabetic patients. PMID- 8453778 TI - Use of seronegative samples for the calibration and reporting of serological enzyme immunoassay results. AB - For evaluation of serological assays, a seropositive reference sample is often arbitrarily assigned a value (EIU) against which test samples are compared. An alternate method, in which seronegative samples are identified by iteration and in turn used to established mean and standard deviation for the quantification (in units of Standard Deviation Ratio (SDR)) of each tested sample, was investigated on 1100 serum samples routinely tested for IgG against Borrelia burgdorferi. Of the 76 specimens that were positive in the EIU system, our computerized SDR method classified 9 as borderline and 67 as positive, none as negative. Of the 917 EIU-negative specimens, the SDR method classified 4 as borderline and 913 as negative, none were SDR positive. We conclude that the SDR has numerous advantages: lower number of borderline specimens found, its computer automation and its more stable results. The method is only suited for larger assays. PMID- 8453779 TI - Enzymes of lysosomal origin in plasma of twin neonates. AB - The levels of some enzymes of lysosomal origin were assayed during days 2 and 5 of life in plasma from 11 sets of twin neonates and from 25 neonates from single pregnancies (13 of weight appropriate for gestational age and 12 small for their gestational age) as controls. The plasma enzyme levels were also determined in the correspondent twin and control mothers 2 days after delivery. N-Acetyl-beta-D glucosaminidase isoenzymes were assayed after chromatofocusing separation. All the plasma enzyme levels were higher in the group of twin neonates and of their mothers than in the respective control groups with differences highly statistically significant for two enzymes, beta-D-galactosidase and alpha-D glucosidase. In neonate plasma lysosomal enzymes are increased at the fifth day of life with respect to the second day. Full term control neonates showed the same enzyme trend. For the N-acetyl-beta-D-glucosaminidase the more significant differences concerned the isoenzyme I2-P (pregnancy). The pattern of the lysosomal enzymes in the twins resembled that of neonates of diabetic mothers who had had no insulin therapy. Since lysosomal enzymes are considered to be particularly sensitive indicators of carbohydrate metabolism abnormalities, we conclude that twin pregnancies are more at risk for these abnormalities than single ones. PMID- 8453780 TI - Preparation of microsome fractions of human myometrium. A comparison of three methods. PMID- 8453781 TI - Red blood cell adenosine deaminase activity in multiple sclerosis. PMID- 8453782 TI - The effect of cyclosporin A on disease progression in proliferative immune complex glomerulonephritis. AB - In rats with the proliferative immune complex glomerulonephritis of chronic serum sickness, kidney function deteriorates in three discrete and readily distinguishable stages: Mild, Moderate, and Severe. The mononuclear cell composition of glomerular inflammation is also different in each stage. The immunosuppressive drug, cyclosporin A, was administered to rats with chronic serum sickness in order to investigate the relationship between glomerular immunopathology and pathophysiology in proliferative immune complex nephritis. When introduced after the onset of proteinuria, daily treatment with cyclosporin A failed to prevent the progression from Moderate to Severe nephritis, which is characterized by the abnormal differentiation and local proliferation of glomerular macrophages, as well as grave deterioration in kidney function. In contrast, when cyclosporin A therapy started before the onset of proteinuria, the course of proliferative glomerulonephritis was altered significantly. Although the levels of proteinuria and macrophage accumulation that are characteristic of the Moderate stage of nephritis were not reduced, progression to Severe nephritis did not occur. The number of glomerular macrophages appeared to increase in two separate phases in this chronic serum sickness model of proliferative immune complex glomerulonephritis. The first phase, which coincided with the onset of proteinuria, did not require T cells and culminated only in moderate hypercellularity and proteinuria. The second increase in the number of glomerular macrophages, which was accompanied by the expression of abnormal macrophage phenotypes, was closely linked to the development of severe kidney insufficiency. The protective effect of cyclosporin A therapy was consistent with, although not conclusive proof for, the hypothesis that local T cell activation may contribute to the progression of proliferative immune complex glomerulonephritis. Since cyclosporin A can also directly influence the responses of macrophages and mesangial cells, the effect of the drug on the course of nephritis in this model might not be related to its immunosuppressive action. PMID- 8453783 TI - Detection of autoantibodies against hGH in sera of idiopathic hypopituitary children. AB - Using reliable displacement radiobinding assay (RBA) and ELISA, the existence of anti-human growth hormone autoantibodies (hGHAA) was confirmed in idiopathic hypopituitary patients with growth impairment. Six of 35 hypopituitary patients (17.1%) and 1/85 (1.2%) control children proved positive for hGHAA by RBA (>control mean + 3 SD). IgG isotype-hGHAA by ELISAIgG (> control mean + 3 SD) were positive for 6/34 (17.7%) and 3/85 (3.5% hypopituitary and control children, respectively. Due to an asymmetry to the right of the ELISAIgG distribution, an alternative cutoff based on a nonparametric method was obtained, and positive results for hypopituitary children increased to 10/34 (29.4%). Three of 34 hypopituitary patients but no control children were positive for hGHAA of IgM isotype. The hGHAA were detected in children with or without perinatal problems. These autoantibodies may represent markers of a major autoimmune process involving a portion of the anterior pituitary and may contribute to the development of hypopituitarism in over 15% of hypopituitary children. PMID- 8453784 TI - Restoration of the thymus in aging mice by in vivo zinc supplementation. AB - A multiparametric study of the thymus was performed in normal aging mice (12-15 months old) submitted to a mild oral zinc supplementation during 3-6 months as compared to age-matched control mice. First, this study demonstrated that in rodents, zinc levels are significantly reduced with aging and can be restored to values close to those observed in young animals after 6 months of zinc supplementation. Second, our data showed that oral zinc administration stimulates thymus growth and partially restores the microenvironmental as well as lymphoid compartments of the organ. Regarding thymic endocrine function, a significant increase in thymulin levels and a concomitant decrease in plasma thymulin inhibitors were observed, suggesting that the age-related decline of thymic function might at least partially be due to extrinsic factors, such as zinc deficiency. The total number of thymic lymphocytes was consistently increased, without significant changes in CD4/CD8 defined thymocyte subsets. Finally, structural changes of the thymus epithelium were also detected, including the disappearance of epithelial cysts frequently observed in old animals, reappearance of a normal pattern of the thymic epithelial cell network, and a decrease in the extracellular matrix network. Taken together, these data suggest that aging-related physiological zinc deficiency induces some relevant changes in thymus structure and function which can be partially corrected by a mild oral zinc supplementation. PMID- 8453785 TI - Milk whey protein fed as a constituent of the diet induced both oral tolerance and a systemic humoral response, while heat-denatured whey protein induced only oral tolerance. AB - Milk whey protein fed to mice as a constituent of the diet elicited a systemic humoral response. The serum antibodies were of the IgG class, which recognized mainly beta-lactoglobulin. Feeding whey protein diet also induced tolerance of systemic immunity (oral tolerance). However, when heat-denatured whey protein was fed, the animals showed only a poor serum response, while oral tolerance was induced to a similar degree as that of native whey protein diet. The results demonstrate the difference of antigen recognition between oral tolerance and oral immunization and suggests that our system using mice may be a useful animal model for food allergy. PMID- 8453786 TI - Rat pancreatic ganglioside expression: differences between a model of autoimmune islet B cell destruction and a normal strain. AB - Islet cell antibodies (ICA) bind antigens expressed in both human and rat pancreatic islets. Biochemical studies have shown that an ICA-autoantigen has the properties of a monosialo-ganglioside migrating between GM2 and GM1 standards (GM2-1). We therefore aimed to isolate and characterize gangliosides from whole pancreas and isolated islets of bio breeding diabetes-prone (BB-DP), bio breeding diabetes-resistant (BB-DR), and Wistar Furth (WF) rat strains. Gangliosides were characterized by TLC, HPLC, diode array analysis, and ganglioside-specific staining. ICA binding was studied by indirect immunostaining. The GM2-1 fraction was present in BB-DP, BB-DR, and WF rat pancreases (11, 17, and 9.5%, respectively, of total ganglioside content). Substantial differences were found in other fractions: in BB-DP pancreas, in addition to GM2-1, the main fractions were GM3 (49%), GD1a (12%), GT1b (5%), and a ganglioside migrating between GM1 and GD3 standards (23%), while in BB-DR pancreas the above components were 71, 5.5, 2, and 4.5%, respectively; in WF pancreas, the main fractions were GM3, GD3, GD1a, GT1b and a trisialoganglioside (GT*) migrating above the GT1b standard (42.7, 7, 20.2, 13.8, and 6.8, respectively). A different pattern of ganglioside expression was found in isolated islets of BB-DP, BB-DR, and WF rats: the GM2-1 fraction represented, respectively, 29.1, 30.4, and 31.6% of total ganglioside content; GM3 51.1, 66, and 68.4%. A fraction migrating between GM1 and GD3 standards was present only in BB-DP and BB-DR islets (19.8 and 3.6%, respectively). ICA-positive human sera reacted with pancreas of all rat strains studied, with similar end-point titers. In conclusion, (1) the GM2-1 ganglioside, in the same way as a putative target antigen of ICA, is equally expressed in BB DP, BB-DR, and WF rat pancreata; and (2) the GM1-GD3 is expressed in higher amounts in BB-DP than in BB-DR pancreas and islets and is absent in WF. PMID- 8453787 TI - Demonstrations of a B-cell population that regulates the immune response in spleens of mice infected with herpes simplex virus type I. AB - A population of B cells that regulates the immune response was demonstrated in splenic mononuclear cells (SMNC) from mice infected with herpes simplex virus type 1 (HSV). SMNC, obtained from mice 3 days after HSV infection at a dose of 100 LD50, exhibited a reduction in the proliferative response of naive SMNC stimulated with various lectins or allogeneic lymphocytes in a 5-day mixed lymphocyte reaction. Cocultivation of naive SMNC with phagocytic cell-free SMNC (M phi-MNC) from infected mice resulted in the inhibition of lymphocytic blast transformation stimulated with various lectins. These cells were characterized as nylon-wool adherent cells that were eliminated by treatment with anti-Ig antiserum, but not anti-Thy 1.2 monoclonal antibody or anti-asialo GM1 antiserum, followed by complement treatment. In addition, the suppressor cell activity was not demonstrated in M phi-MNC obtained from HSV-infected CBA/CaHN-xid/J mice, which contain a congenital B-cell deficiency. These results suggest that, in addition to suppressor T cells, a population of B cells, which can inhibit lymphocyte proliferations upon stimulation with lectins and alloantigens, might be generated in spleens of mice following HSV infections. PMID- 8453788 TI - The use of monozygotic and dizygotic twins to estimate the effects of inheritance on the levels of immunoglobulin isotypes and antibodies to phosphocholine. AB - In the elderly there is a pronounced increase in susceptibility to infectious disease. Evidence for particular immune deficits that result in susceptibility to specific agents is lacking, however, and there is little information on the degree to which differences in the susceptibility among the elderly are due to genetic versus environmental effects. A strong association has been observed between eventual fatal pneumonia and elevated levels of IgM antibody to phosphocholine (PC) levels at age 70. In this study we evaluated the heritability of IgM and IgG antibody levels to phosphocholine in the elderly using monozygotic and dizygotic male twins. We observed genetic regulation of serum levels of IgM antibody to PC, a finding which suggests that susceptibility of the elderly to fatal pneumonia may be heritable. Levels of total IgM were under separate genetic control and there was no genetic effect on IgG and IgA levels or levels of IgG antibody to phosphocholine. PMID- 8453789 TI - Immunoadsorption in acquired angioedema: a therapeutic misadventure. PMID- 8453790 TI - T cell recognition of human tumors: implications for molecular immunotherapy of cancer. AB - Based on experimental and clinical data, it appears that human T cells are capable of mediating tumor cell destruction and, thus, are potentially important for immunotherapy of cancer. To date, neither the mechanisms responsible for T cell-mediated tumor cell destruction in vivo nor in vitro correlates of clinical responses in cancer patients treated with immunotherapy have been defined. Nevertheless, substantial evidence for the presence in cancer patients of specific autotumor (AuTu) responses mediated by T lymphocytes has accumulated. T cells recognize tumor-associated antigens (Ags) by means of clonally distributed T cell receptors (TCR). Molecular analysis of the preferential use of the TCR V beta gene families for recognition of Ags (tumor-associated peptides) by circulating or tumor-infiltrating T cells indicates that clones of AuTu-reactive effector T cells are present in patients with cancer. Recent advances in the characterization of tumor peptides bound to the MHC class I or class II molecules, definition of allele-specific consensus motifs, and availability of computer programs for modeling of T cell Ag interactions now allow for identification of specific T cell-reactive tumor peptide epitopes from proteins with known amino acid sequences. Also, the tumor-bearing host appears to be able to discriminate between tolerance to self, antitumor responses, and autoimmune phenomena. This type of a regulatory mechanism has not been precisely defined, but it might be surmised that immunosuppression, which is commonly seen in the tumor microenvironment, may result from attempts by the host to dampen or control self-reactivity rather than from tumor-induced down-regulation of T cell responses to escape immune surveillance. To progress toward molecular immunotherapy of cancer and to overcome tumor-host-induced immunosuppression in the tumor microenvironment, a better understanding of T cell-tumor interactions is necessary. It might be possible in the future to select for therapy clones of human T cells expressing the desired TCR and reacting with specific tumor peptides. It might also be feasible to reduce or eliminate tumor-mediated immunosuppression of T cell responses. Such selective molecular interventions in human cancers will depend on current advances in the definition of tumor Ag epitopes which elicit strong and sustained T cell responses. PMID- 8453791 TI - How to diagnose spondylarthropathy? PMID- 8453792 TI - MRI and SPECT investigations of the CNS in SLE patients. AB - Twenty-two SLE patients were examined with Magnetic Resonance Imaging (MRI) and Single Photon Emission Computed Tomography (SPECT). Multifocal areas of cerebral blood flow (CBF) defects were found in 81.8% of the patients. These alterations were present in patients with severe neurological disorders, in those with neuropsychiatric symptoms only, and also in asymptomatic cases. Anticardiolipin antibodies (aCL) were detected in all patients, but no correlation was found between serum aCL positivity and neurological involvement. The high incidence of cerebral blood flow disorders found in asymptomatic patients, and their poor correlation with the MRI alterations suggest a primary defect of CBF in these patients. PMID- 8453793 TI - Gastric involvement in primary Sjogren's syndrome. AB - Gastric involvement was investigated in twenty Italian patients with primary Sjogren's syndrome (pSS). Gastric complaints were present in 11 cases (55%) and endoscopic abnormalities in 10 (50%) including 2 cases with active duodenal ulcer. Only two patients (10%) showed moderate chronic atrophic gastritis (AG), while most (85%) had superficial gastritis (SG). No correlations were found among endoscopy, histology and gastric symptoms. Mean serum group I pepsinogen (PG I) levels were significantly higher (p < 0.01) and PG I concentrations in the fundus of the stomach were significantly lower (p < 0.05) in pSS patients than in a matched control group of dyspeptic subjects. Serum and antral gastrin levels were elevated in 3 cases with pSS (15%) including the two with AG, although the mean levels were not different from the controls. Antibodies to gastric parietal cells (PCA) were detected in two cases (10%) including 1 with AG. The present study contradicts previous reports claiming that AG with hypopepsinogenemia is a prominent feature in Sjogren's syndrome. We suggest that, at least in Italian patients, pSS is often associated with SG and high PG I levels. PMID- 8453794 TI - Expression of complement receptors (CR1 and CR3) and Fc gamma RIII on polymorphonuclears from patients with spondylarthropathies. AB - We assessed the expression of complement receptors (CR1 and CR3) and Fc gamma RIII on unstimulated and FMLP activated polymorphonuclears (PMNs) by indirect immunofluorescence and flow cytometry using CD35 (CR1), CD11b (CR3) and CD16 (Fc gamma RIII) monoclonal antibodies in 24 patients with spondylarthropathies (SpA) and in 18 healthy subjects. SpA patients were classified into 3 groups according to the severity of the disease (severe = asymmetrical peripheral joint involvement and permanent limitation of spine motion; moderate = one of the two items, mild = none of the items). CR1 and Fc gamma RIII expression were significantly decreased in patients with mild SpA, whereas CR1 and CR3 expression were significantly increased in patients with severe disease as compared to control subjects. In patients with mild disease, CR1 expression increased after FMLP activation, but remained significantly lower than in control subjects. The results were confirmed by immunoelectroblotting. These findings suggest that membrane and intracellular pools of CR1 and CR3 may contribute to the clinical modulation of the spondylarthropathies. PMID- 8453795 TI - A randomised, double-blind study of cicaprost, an oral prostacyclin analogue, in the treatment of Raynaud's phenomenon secondary to systemic sclerosis. AB - Cicaprost is a new synthetic prostacylin analogue which is metabolically stable and bioavailable after oral administration; in previous studies it has been shown to have vasodilator antiplatelet effects. In this pilot study, we investigated the clinical efficacy of and patient tolerance to two dosage levels of cicaprost (2.5 micrograms tds and 5 micrograms tds) in the treatment of Raynaud's phenomenon secondary to systemic sclerosis (SSc). This was a three centre, double blind, placebo controlled study of 49 patients carried out over four winter months. For a period of 10 days, 16 patients were given a placebo, 16 received cicaprost 2.5 micrograms tds and 17 received cicaprost 5 micrograms tds. Response was assessed based on the total number and duration of Raynaud's attacks, the average severity of the attacks, the number of painful attacks as a proportion of all attacks, a digital ulcer count, and the patients' opinion of the treatment. Although the clinical and laboratory parameters of digital vasospasm did not show statistically significant improvement in those who received cicaprost compared with those on the placebo, the severity of attacks lessened in the patients who received cicaprost 5 micrograms tds, and a statistically significant difference was seen in the average severity at week 2 post-treatment (p = 0.02). The apparent lack of overall significance was probably related to the short treatment period and relatively low doses of cicaprost used in this exploratory study. Longer studies with dose titration are probably needed to demonstrate the beneficial effects, if any, of cicaprost in patients with Raynaud's secondary to SSc, and these are being planned. PMID- 8453796 TI - Geographical clustering of scleroderma in a rural area in the province of Rome. AB - A geographical cluster of scleroderma and scleroderma-related features was identified in a rural area in the province of Rome. Two patients with scleroderma, three with CREST syndrome and one with eosinophilic fasciitis were living in a village where the total population included 572 persons of voting age. No kindred relationships were demonstrable among these patients. Clinical features of scleroderma such as Raynaud's phenomenon, bilateral hand edema, and digital scars were detected in an additional 10 cases. A group of apparently healthy subjects with scleroderma-related serological abnormalities (circulating antinuclear and anticentriole autoantibodies) was also identified in the village. No disease-associated HLA antigen in the patients nor genetic differences between patients and healthy subjects living in the same village were detected by HLA typing. Some still unidentified environmental factors acting on genetically predisposed subjects may be responsible for the clustering of the disease seen in this study. PMID- 8453798 TI - Observations on diagnostic criteria for ankylosing spondylitis. AB - The Rome and New York criteria for ankylosing spondylitis (AS) have been compared in a clinical sample of patients with this disease and other joint disorders. The best individual clinical discriminator was the first Rome criterion, low back pain and stiffness lasting for three months and, in contrast, the New York criterion of dorsolumbar pain performed poorly. On the other hand, the more stringent New York formulation of lumbar spine limitation in all three planes came out as a better discriminator than its Rome counterpart. Both sets of radiographic criteria performed well. Ethical problems remain, which suggests that new criteria need to be developed for use in population surveys. Peripheral joint involvement was also assessed, but there did not appear to be any merit in taking this into account in any subsequent revision of diagnostic criteria for AS. PMID- 8453797 TI - The effect of bed rest and intra-articular steroids on the acute phase response in rheumatoid arthritis. AB - The impact of therapeutic interventions on the disease process in patients with rheumatoid arthritis (RA) is complex. The effect on the acute phase response was studied in 25 in-patients on imposed bed rest, who were randomised to treatment with (n = 12) or without (n = 13) intra-articular steroids. C-reactive protein (CRP), ESR and IgA alpha-1 antitrypsin complex levels were measured on admission and on days 3 and 5. Levels at onset were not different between groups. At day 3 and day 5, a significant (p < 0.001) fall in CRP was seen only in the intra articular steroid group. Other cytokine and disease parameter measures did not alter during the study period (although IL-6 and CRP correlated at onset in all 25 patients). The mean duration of the hospital stay was longer for the patients treated with bed rest only. Thus, bed rest when combined with intra-articular steroids produced a rapid systemic effect, while bed-rest alone did not have an effect on the acute phase response over this short time scale. PMID- 8453799 TI - Serum osteocalcin and calcitropic hormones in a homogeneous group of patients with rheumatoid arthritis: its implication in the osteopenia of the disease. AB - Different mechanisms may play a role in the pathogenesis of the generalized osteopenia found in rheumatoid arthritis (RA). We measured the calcium, osteocalcin (BGP), parathyroid hormone (PTH), calcitonin (CT) and 25(OH)D3 levels as well as urine 24 hr calcium, Ca/Cr and OHP/Cr in a homogeneous group of 30 non disabled patients (10 men, 8 premenopausal women and 12 postmenopausal women) recently diagnosed as having RA (disease duration 4 to 6 months). They had normal serum levels of vitamin K, were not on previous or present treatments known to interfere with calcium metabolism, and were not pregnant if females of fertile age. The group was compared with an age-matched control group of 32 healthy subjects (10 men, 8 premenopausal women and 14 postmenopausal women). We observed significantly decreased levels of 25(OH)D3 (29.9 +/- 9.9 vs 48.7 +/- 12.1 ng/mL; p < 0.005) and significantly increased levels of urine OHP/Cr (2.24 +/- 0.71 vs 1.56 +/- 0.82 mg/mg; p < 0.001) in the RA group. No differences in these two parameters were found between the three subgroups of RA patients. Male RA patients showed decreased levels of serum BGP (7.3 +/- 1.0 vs 8.2 +/- 1.7 ng/mL; p < 0.01). The remaining parameters did not differ significantly between RA patients and controls. These data suggest that the generalised osteopenia found in RA may be a consequence of increased bone resorption without a concomitant increase in bone formation, perhaps related to mechanisms inherent to the disease. PMID- 8453800 TI - Interlaboratory variability of the antiperinuclear factor (APF) test for rheumatoid arthritis. AB - The antiperinuclear factor (APF) test is as sensitive and specific for rheumatoid arthritis as the classical rheumatoid factor tests. Five European laboratories decided to perform a consensus study on the interlaboratory variability of the APF test. They used different donor cells, different conjugates and different criteria for positivity. However, the results differed by not more than one two fold dilution step, when expressed in international units using WHO reference rheumatoid arthritis serum as the standard. PMID- 8453801 TI - Influence of the bacterial flora on collagen-induced arthritis in susceptible and resistant strains of rats. AB - Collagen-induced arthritis is an experimental model for rheumatoid arthritis which can be elicited in susceptible strains of rats by intradermal injection of native type II collagen. In order to investigate whether bacterial flora may alter the pathogenic response to type II collagen, we have immunized germ-free (GF) male rats from either highly resistant Fisher (F344) or highly susceptible Dark Agouti (DA) strains. The disease was markedly enhanced in GF DA as compared to conventional (CV) DA rats. The humoral response was also stronger in GF rats of both strains. Neither GF nor CV F344 developed arthritis, although GF F344 exhibited later inflammation of the tail. These data support a suppressive influence of bacterial flora on collagen-induced arthritis. PMID- 8453802 TI - Arthritis associated with primary agammaglobulinemia: new clues to its immunopathology. AB - Primary agammaglobulinemia is a rare disorder which is associated with articular symptoms in 11% of patients. Septic arthritis may occur, but often patients complain of chronic oligoarthritis and have a clinical presentation similar to rheumatoid arthritis. We report 2 cases of primary agammaglobulinemia in adults, associated with non-erosive chronic arthritis. Peripheral blood lymphocyte phenotyping showed a predominance of CD8 lymphocytes with a CD4/CD8 ratio < 1. We did not find any abnormalities in cellular immunity. A histological study of the synovium showed chronic synovitis with perivascular CD8 lymphocyte infiltrates. Intravenous infusion of immunoglobulins resulted in a dramatic improvement in the arthritis in both cases. In one patient we noticed a decrease in CD8 lymphocytosis. These results suggest that CD8 lymphocytes are involved in the pathogenesis of the arthritis associated with agammaglobulinemia. PMID- 8453803 TI - Research in rheumatology: a six-month review of selected medical journals. AB - Research in rheumatology has dramatically increased in the past decades, and researchers can choose among over 20,000 journals to publish their findings. The purpose of this study was to examine the current extent and impact of rheumatological research on the medical literature. The tables of contents of 1,158 biomedical journals were analyzed during a 6-month period and those with a rheumatology-related title were selected. In total, 2,549 articles from 406 journals were related to rheumatology. The 10 rheumatology journals selected for the analysis contained 769 articles (30% of the total); thus, over two-thirds of the information on rheumatology topics was provided by non-rheumatology journals. Over 65 different journals included information about rheumatoid and systemic lupus erythematosus. It is concluded that research in rheumatology is extensive and widespread. Since articles in rheumatology are scattered over a variety of journals, it is suggested that the periodic publication of a rheumatology reference index may assist rheumatologists in updating information from various sources. PMID- 8453804 TI - Arthritis surgery. PMID- 8453805 TI - Amyloidosis in juvenile chronic arthritis: a morbidity and mortality study. AB - A retrospective study of 79 juvenile arthritic patients with reactive amyloidosis for a mean of 10 years (3 months-24.25 years) from the onset of amyloidosis was performed. Eighty percent of those treated with chlorambucil (n = 57) were alive compared with 23.5% of patients not treated with chlorambucil (n = 19) 10 years after diagnosis. Renal failure was the cause of death in 82.3% and infection in 11.7%. Side effects included one chlorambucil-treated patient who developed acute leukaemia, and seven patients who developed severe leucopenia and four thrombocytopenia. Fifteen patients are no longer on cytotoxic therapy and are in remission. Analysis of their fertility status showed that there were 5 normal births in 3 women and 2 terminations of pregnancy in 23 chlorambucil-treated women of child bearing age. Six women had ovarian failure. None of the male patients fathered a child. PMID- 8453806 TI - Report from a symposium on corticosteroid therapy in juvenile chronic arthritis. PMID- 8453807 TI - Gingival and periodontal health in Sjogren's syndrome and other connective tissue diseases. PMID- 8453808 TI - Serum aldolase and lactate dehydrogenase levels in the eosinophilia myalgia syndrome. PMID- 8453809 TI - Hydrops of gallbladder requiring cholecystectomy in Kawasaki syndrome. PMID- 8453810 TI - The diagnosis of pseudoseizures. AB - Increasing experience with intensive monitoring of patients with intractable seizures has shown that a significant number of patients presents with pseudoseizures (psychogenic seizures). While in a majority of the patients differential diagnosis should be obvious, in some patients diagnostic error may occur. This is the case if the physician is unfamiliar with uncommon seizures, if the patient presents with atypical or bizarre attacks, and if interictal and/or ictal EEG are normal. Comparative studies of patients with true convulsive seizures and patients with pseudoseizures have revealed some 'typical' ictal features of pseudoseizures. Of these, longer ictal duration, less stereotypy, asynchronous extremity movements, atypical vocalization, alternating head movements and pelvic thrusting are the most characteristic. Many exceptions exist, however, since many patients with complex partial seizures (mostly of frontal origin) may present with similar ictal features. The final diagnosis of pseudoseizures is based upon integration of numerous data including careful seizure history, results of intensive video EEG monitoring and electroclinical correlation by experienced observers. Psychiatric and personality examination, different techniques of suggestion and determination of serum prolactin may provide additional diagnostic evidence. PMID- 8453811 TI - Heterogeneous findings in four cases of cerebellar ataxia associated with hypogonadism (Holmes' type ataxia). AB - We report four sporadic cases of cerebellar ataxia associated with hypogonadism. All patients were female. The neurological symptoms appeared in the first three decades. Apart from ataxia, the most frequent features were nystagmus, dysarthria, mental impairment, brisk tendon reflexes, skeletal deformities, peripheral neuropathy, and tremor. Neuroimaging studies showed constant cerebellar atrophy, in some instances associated with involvement of either grey or white cerebral matter. Neurophysiological studies demonstrated an axonal neuropathy. Endocrine evaluation showed heterogeneity of the hypogonadism, which was hypogonadotrophic in one patient and hypergonadotrophic in the other three. One patient had partial deficiency of muscle cytochrome c oxidase. The syndrome appears to be a heterogeneous multisystem disorder and in some cases a mitochondrial metabolism deficiency could be suspected. PMID- 8453812 TI - Systemic lupus erythematosus: neuropsychiatric signs and symptoms related to cerebral MRI findings. AB - A 76.2% prevalence of abnormalities was found in the cerebral MR scans of 21 patients with systemic lupus erythematosus (SLE). These patients were enrolled in the study consecutively as they presented at an immunological out-patient unit. They were not selected on the basis of neuro/psychiatric findings. Circumscribed non-periventricular brain lesions were found in 12 patients (57.1%), mainly in the frontal white or gray matter. Periventricular lesions directly adjacent to the ventricles were detected in 10 patients (47.6%). Eleven patients (52.4%) showed signs of cerebral atrophy. MRI detected more lesions in patients with clinically focal CNS lupus than in patients with seizures or patients without clinically localized findings. Eleven patients had abnormal neuropsychiatric CNS findings; there was no clear correlation between neuropsychiatric signs and symptoms and brain abnormalities as shown by MRI. Seven patients had asymptomatic lesions. Cerebral MRI proved to be the method of choice for the non-clinical diagnosis of neuropsychiatric SLE. PMID- 8453813 TI - Hypertension encephalopathy after liquorice ingestion. AB - A 15-year-old boy is reported who developed a hypertension encephalopathy after ingestion of 0.5 kg liquorice candy. He recovered completely in the course of 5 months. PMID- 8453814 TI - Extensive cervical intradural and intramedullary lipoma and spina bifida occulta of C1: a case report. AB - A 17-year-old boy presented with a 1-year history of progressive gait difficulties and slowing of fine hand movements. On neurological examination there was tetraspasticity, bilateral pes equinovarus and a decreased position sense in the feet. CT and MRI scan of the cervical spine demonstrated a spina bifida occulta of C1, an extensive intradural lipoma from the foramen magnum to C4 with a small intramedullary portion at C3, and a distal syringomyelia reaching down to D12. After excision of the extramedullary portion of the lipoma, there was a marked improvement of the gait and a reduction of the spasticity. PMID- 8453815 TI - A case of acute encephalopathy after iohexol lumbar myelography. AB - A case of acute encephalopathy after lumbar myelography is reported in a female aged 26 years. Fourteen hours after the procedure, the patient developed coma (GCS 6) and had generalized slowing of EEG activity. This state lasted about 12 h, followed by gradual and full recovery. PMID- 8453817 TI - Spinal intramedullary cavernous angioma in a patient with Down's syndrome. AB - A rare case of cervical intramedullary cavernous angioma in a 30-year-old man with Down's syndrome is presented. A review of the literature showed this to be the first reported case. Magnetic resonance imaging was diagnostic. A myelotomy was done and multiple biopsies were taken. The patient deteriorated neurologically and later died due to severe chest infection. The presentation, management and prognosis of this condition are discussed. PMID- 8453816 TI - Herpes simplex encephalitis mimicking mumps. AB - A 16-year-old male diabetic patient presented with bilateral salivary gland swellings followed by encephalitis. The EEG did not show the characteristic periodic lateralising epileptic discharges. Neuro-imaging disclosed compromise of temporal and frontal lobes as well as brain stem which correlated well with his clinical deterioration. Serology and frontal brain biopsy were positive for herpes simplex virus while mumps titers were not significant. Despite delayed acyclovir therapy, the patient recovered enough to be discharged home with a permanent pseudobulbar palsy. Herpes simplex encephalitis involving zones other than temporal lobes is exceptional. To our knowledge, there are no reported cases of pseudobulbar palsy as a sequelae of HSV encephalitis. PMID- 8453818 TI - Acute disseminated encephalomyelitis probably related to a Mycoplasma pneumoniae infection. AB - A 36-year-old woman was suffering from acute disseminated encephalomyelitis, which had been preceded by a febrile illness. Brain CT showed diffuse white matter hypo-attenuation. Electroencephalography initially revealed altered non REM sleep followed by diffuse slowing. Brain stem auditory evoked potentials showed interwave delay, while pattern visual evoked potentials were normal. The patient made a full recovery and the CT scan and EEG normalized. Serological evidence of Mycoplasma pneumoniae was present. PMID- 8453819 TI - Hypertrophic cranial pachymeningitis causing progressive unilateral blindness: MR findings. AB - A case of hypertrophic cranial pachymeningitis is described and the MR appearance presented. A gadopentetate-dimeglumine-enhanced MR scan enhanced markedly suggesting thickening and inflammation of dura and falx cerebri. The patient, a 72-year-old elderly man, had surprisingly little clinical abnormality. His only neurological manifestation was progressive unilateral blindness. The exact cause of his pachymeningitis was unknown, though neither rheumatoid arthritis nor other collagen disease was completely excluded. PMID- 8453820 TI - Acinetobacter, an infrequent cause of community acquired bacterial meningitis. AB - A 19-year-old previously healthy woman developed meningitis due to Acinetobacter calcoaceticus. This is a Gram-negative coccobacillus belonging to the family Neisseriaceae. Most reported cases of Acinetobacter meningitis were hospital acquired and due to strains highly resistant to amoxycillin. Our patient was treated with amoxycillin and recovered without sequelae. PMID- 8453822 TI - Patient-controlled analgesia. Pharmacokinetic and therapeutic considerations. AB - The opioid analgesic agents exhibit relatively large pharmacokinetic differences between drugs, and there is substantial pharmacokinetic and pharmacodynamic variability across subjects or patients with each agent. The advent of patient controlled analgesic administration techniques and their widespread use in contemporary pain management, especially in postsurgical and cancer patients, has decreased the unfortunate impact of interpatient variability on achieving the optimal balance between pain relief and opioid adverse effect intensity. The improvements in pain management provided by patient-controlled analgesia do not, however, decrease the importance of knowledge of opioid pharmacokinetics towards enlightened use of these drugs and attainment of maximal benefits from them in any patient. Future improvements in patient-controlled analgesia technology will probably be based on the pharmacokinetic behaviour of different opioid analgesic agents in specific receptor-containing regions. Finally, physicochemical and pharmacokinetic characteristics of these agents are important determinants of the speed of onset of effects, duration of action and spinal selectivity of epidurally and intrathecally administered analgesics. Thus, effective patient controlled analgesia depends on an understanding of the differential pharmacokinetics of opioids self-administered by a variety of possible modes. PMID- 8453821 TI - Comparative pharmacokinetics of antiviral nucleoside analogues. AB - The recent development of nucleoside analogues with antiviral activity has expanded the small but useful armamentarium for the treatment of certain viral diseases such as the human immunodeficiency virus, cytomegalovirus and others. Their intracellular site of action and need for sequential phosphorylation require that traditional pharmacokinetic parameters be used in conjunction with an understanding of intracellular metabolism when designing dosage regimens. This review summarises the available pharmacokinetic literature for zidovudine, didanosine, zalcitabine, aciclovir, ganciclovir, vidarabine and ribavirin. After oral administration, didanosine, aciclovir and ribavirin are < 50% bioavailable and ganciclovir is < 6% absorbed. In contrast, zidovudine and zalcitabine are > 60% bioavailable, although zidovudine undergoes considerable and variable first pass hepatic glucuronidation while zalcitabine has no first-pass effect. Zidovudine, zalcitabine and didanosine are absorbed rapidly in the fasted state, with peak plasma concentrations exceeding their respective in vitro antiretroviral inhibitory concentrations. All reviewed agents except ribavirin have a relatively short plasma half-life (approximately 0.5 to 4h), with each agent demonstrating a different intracellular enzymatic activation scheme. For example, the rate-limiting step for formation of zidovudine triphosphate is the conversion of the monophosphate to the diphosphate, while didanosine is ultimately converted to dideoxyadenosine triphosphate which has the longest intracellular half-life (approximately 12 to 24h) among these agents. These drugs are not highly protein bound and they distribute into tissues with an apparent volume of distribution at steady-state ranging from 0.3 to 1.2 L/kg. They vary in the extent to which they enter cerebrospinal fluid, ranging from a low of < 25% for didanosine to a high of > 70% of a concurrent plasma concentration for ribavirin and vidarabine. These agents also vary with regard to degree of renal excretion of the parent drug, with the lowest noted for vidarabine (1 to 3%) and the highest for zalcitabine (approximately 75%) and ganciclovir (> 90%). With the increasing number of clinically useful nucleoside analogues, it is essential for the clinician to appreciate the subtle differences among these agents to ensure that optimal therapeutic outcomes may be attained with minimal toxicity. PMID- 8453824 TI - Pharmacokinetics of fluvoxamine maleate in patients with liver cirrhosis after single-dose oral administration. AB - The pharmacokinetics of fluvoxamine maleate were investigated in 13 patients with biopsy-proven liver cirrhosis. They received a single oral 100mg dose as an enteric-coated tablet, and plasma samples were collected up to 168h after administration. Geometric mean values for peak plasma concentrations and area under the plasma concentration-time curves (AUC) were 39 micrograms/L and 1338 micrograms.h/L, respectively. Mean (+/- SD) elimination half-life (t1/2) was 25 +/- 11h, and increased with higher plasma bilirubin levels, although no relationship between bilirubin and AUC was observed. AUC was about 50% higher in patients than in healthy volunteers from another similar study. This was mainly because of a longer t1/2. Although there is a great overlap between AUC values of fluvoxamine in patients and healthy volunteers, it is nevertheless concluded that in patients with signs of active liver disease, e.g. raised bilirubin, it is wise to lower the initial daily dose and to carefully monitor the patient during subsequent upward dose adjustments. PMID- 8453823 TI - Pharmacokinetics and pharmacodynamics of clozapine. AB - The introduction of clozapine has given clinicians a unique agent for treating patients with schizophrenia that is refractory to other neuroleptics. Despite its efficacy, the drug continues to be prescribed with trepidation due to the incidence of agranulocytosis. This article reviews the pharmacokinetic and pharmacological properties of clozapine and the clinical implications for monitoring plasma concentrations. Various assays have been developed for clozapine that include gas-liquid chromatography, radioimmunoassay and high performance liquid chromatography. Only a few studies have examined the pharmacokinetics of clozapine in patients with schizophrenia. These studies have revealed a wide interpatient variability in pharmacokinetic parameters that include: time to reach peak plasma concentrations 1.1 to 3.6h; elimination half life 9.1 to 17.4h; clearance 8.7 to 53.3 L/h; and a volume of distribution of 1.6 to 7.3 L/kg. Clozapine is metabolised via the hepatic microsomal enzyme system into 2 principle metabolites: demethyl-clozapine and clozapine N-oxide. Urine samples have reported the ratio of clozapine:demethyl:N-oxide to be 1:1:2. The clozapine N-oxide binding affinity with 3H-haloperidol was 4 times lower than clozapine and its conversion back to clozapine is hypothesised. Although the exact pharmacological mechanism of action of clozapine is not fully understood, the drug does possess significant binding affinity for different dopamine receptors, with recent evidence supporting binding to the D4 receptor subtype. Clozapine transiently increases serum prolactin levels with minimal changes in homovanillic acid plasma levels. Limited studies investigating the relationship between clinical response and plasma clozapine concentrations have investigated the range between 100 and 800 micrograms/L. In the treatment of patients with refractory schizophrenia, a minimum concentration of 350 micrograms/L was suggested as needed. The occurrence of agranulocytosis could have a genetic basis and patients should be rigorously monitored during treatment. The incidence of tardive dyskinesia and extrapyramidal side effects is minimal. Clozapine can lower the seizure threshold in a dose- and time-dependent manner. Careful patient selection and monitoring are required when clozapine therapy is used in patients with schizophrenia. PMID- 8453825 TI - Plasma protein binding of lidocaine and warfarin in insulin-dependent and non insulin-dependent diabetes mellitus. AB - We examined the plasma protein binding of an acidic drug (warfarin bound to albumin) and a basic drug [lidocaine (lignocaine) bound to alpha 1-acid glycoprotein] in 15 patients with insulin-dependent diabetes mellitus (IDDM) and 15 matched controls. We also examined protein binding of warfarin and lidocaine in 30 patients with non-insulin-dependent diabetes (NIDDM) and 25 controls. Compared with control, the binding of both warfarin (98.81 +/- 0.02 vs 98.57 +/- 0.03%, mean +/- SEM) and of lidocaine (69 +/- 2 vs 58 +/- 2%) was significantly reduced in IDDM. This group had lower concentrations of both albumin and alpha 1 acid glycoprotein (AAG), achieving statistical significance vs control for albumin only. In the patients with NIDDM, who had a similar level of glycosylated haemoglobin, while there was no significant difference in the binding of lidocaine there was a significant increase in warfarin binding compared with the control population (99.01 +/- 0.03 vs 98.82 +/- 0.04%). This study suggests that binding of both acidic and basic drugs is altered in both IDDM and NIDDM. PMID- 8453827 TI - Urinary tract infections and the uncircumcised state: an update. AB - In a two-part study of the circumcision status of boys with urinary tract infections (UTIs), we reviewed the occurrence of UTIs in 209,399 infants born in US Army hospitals worldwide from 1985 to 1990. During the first year of life, 1,046 (0.5%: 550 girls and 496 boys) were hospitalized for UTIs. Noncircumcised male infants had a 10-fold greater incidence of infection than did circumcised male infants. The frequency rate of circumcision rose significantly, from 70.3% to 80.2%, during the study period. Among uncircumcised boys younger than 3 months with UTIs, 23% had concomitant bacteremia involving the same organism. The second part of the study consisted of a meta-analysis of all nine previous reports on the circumcision status of boys with UTIs. These studies revealed a fivefold to 89-fold increased risk of infection in uncircumcised boys; the combined data yielded a 12-fold increase in UTIs in this population. Parents should be told of the lower risk of UTIs for circumcised boys during informed-consent counseling. PMID- 8453826 TI - Insulin use in pregnancy. Clinical pharmacokinetic considerations. PMID- 8453828 TI - The psychological functioning of children with hypercholesterolemia and their families. A preliminary investigation. AB - The medical aspects of hypercholesterolemia have been studied extensively, but little research has addressed the psychological aspects of screening and treatment of the disease. This study compared the functioning of 32 children, ages 8 to 11 years, and their respective families. Eighteen children had hypercholesterolemia, and 14 had normal cholesterol levels. Responses on several psychological measures showed no differences between the two groups. Thus, hypercholesterolemia appears not to cause major psychological difficulties for children and their families. Analysis showed that those families reporting good dietary choices were more cohesive, more organized, and less conflictual than families who reported fair-to-poor dietary choices. Thus, family functioning may be related to dietary practices. These findings suggest that concern about negative psychological consequences of cholesterol screening is unfounded. Also, families for whom dietary modifications are critical may benefit from family centered treatment as well as dietary counseling. PMID- 8453829 TI - What is fever? Normal temperature in infants less than 3 months old. AB - To determine the normal temperature of healthy infants, we studied 691 infants less than 3 months of age being seen for regularly scheduled well-baby visits. All temperatures were taken rectally with an electronic thermometer. The mean temperature was 37.5 degrees C +/- 0.3 degrees C. Using a cutoff of 2 standard deviations (SD) above the mean, fever would be defined as a temperature > or = 38.1 degrees C. The 95th percentile was 38.0 degrees C, and > or = 38.1 degrees C would correspond to values above the 95th percentile. The most widely used definition of fever at present is a temperature > or = 38.0 degrees C; by this definition, 6.5% of these well infants would be considered to have a fever. A significant rise in temperature with age was noted. For infants from birth to 30 days old, 2 SD above the mean was 38.0 degrees C; for those 31 to 60 days old, it was 38.1 degrees C; and for those 61 to 91 days old, it was 38.2 degrees C. Similarly, the 95th percentile was 37.9 degrees C, 38.0 degrees C, and 38.1 degrees C, respectively. Temperature also varied significantly with the season of the year, being higher in the summer (2 SD above a mean = 38.3 degrees C) than in the winter (2 SD above a mean = 38.0 degrees C). Fever should be defined as a temperature > or = 38.0 degrees C in infants less than 30 days of age, > or = 38.1 degrees C in 1-month-olds, and > or = 38.2 degrees C in 2-month-olds. PMID- 8453830 TI - Use of abdominal and pelvic ultrasound in the evaluation of chronic abdominal pain. AB - The value of sonography in assessing chronic abdominal pain (CAP) in children, the characteristics of CAP, and the local pediatrician's practice in evaluating CAP are reported. Fifty-seven patients with CAP had abdominal and/or pelvic sonography; 56 were normal. One sonogram showed an ovarian cyst on the side opposite the CAP; the cyst later resolved. Pain was usually localized in the periumbilical area (56%). Follow-up data were obtained from referring physicians and patients' medical records. No serious diagnosis related to CAP was missed. After six months, CAP had resolved in 43% of patients. Of the responding physicians, 61% indicated they would have used more and costlier contrast studies if ultrasonography had been unavailable. PMID- 8453831 TI - Status of immunization and iron nutrition in New York City homeless children. AB - A retrospective review of the hospital records of New York City children aged 6 months through 6 years showed that 63 homeless children had a higher rate of immunization delay than an age- and sex-stratified sample of 63 domiciled children living at the same federal poverty level. In a logistic regression model, this difference persisted after controlling for sex, age, ethnicity, presence of chronic illness, and reason for referral. In a 6-month- to 2-year-old subgroup, homeless and domiciled children had equal rates of anemia, but homeless children were more likely to have elevated erythrocyte protoporphyrin (EP) levels consistent with iron deficiency. This difference, too, persisted after controlling for the same confounding factors. Elevated EP levels and immunization delay were likely to coexist in the homeless children. The higher rate of immunization delay is compatible with the occurrence of measles outbreaks in some New York City shelters. The higher rates of iron deficiency may reflect overall poor nutrition. All these findings have significant implications for the design of health-care programs for homeless children. PMID- 8453832 TI - Inadequate immunizations. Identification using clinic charts. AB - Immunizations are cost-effective measures for assuring public health. However, recent outbreaks of measles, mumps, and pertussis underscore the inadequacy of current immunization programs. A model identifying those children who are likely to be inadequately immunized could focus the use of limited health funds. A retrospective examination of the medical charts of 101 children in a large inner city clinic was undertaken to determine if specific factors were associated with inadequate immunization status. Fifty percent of the children were inadequately immunized by 18 months of age (no measles-mumps-rubella or fewer than three diphtheria-pertussis-tetanus vaccinations). Logistic regression analyses showed that older maternal age, no recurrent or chronic illnesses, and vaginal delivery were independently associated with inadequate immunization status. However, on many charts, information on maternal, social, and environmental variables was incomplete. The increasing use of structured medical charts will enhance data collection and the determination of an appropriate index. A prospective study of the variables identified, along with standardization of medical records and inclusion of social history data, is necessary to further investigate the utility of screening criteria for inadequate immunizations. PMID- 8453833 TI - Are routine immunizations in the emergency department a realistic goal? PMID- 8453834 TI - Problems with vaccination coverage in the United States. PMID- 8453835 TI - Higher adenosine dosage required for supraventricular tachycardia in infants treated with theophylline. PMID- 8453836 TI - Multiple cerebral venous thromboses in a child with ulcerative colitis. PMID- 8453837 TI - Are you and your waiting room's televised "expert" saying the same thing? PMID- 8453838 TI - Simultaneous hyperphosphatasemia and erythroblastopenia of childhood. PMID- 8453839 TI - Tall stature. An atypical phenotype in Prader-Willi syndrome. PMID- 8453840 TI - Treatment of neonatal Graves' disease with sodium ipodate. A case report. PMID- 8453842 TI - The association of Chiari type I malformation and neurofibromatosis type 1. AB - The association of neurofibromatosis type 1 (NF1) with Chiari malformations of the cerebellum and brain stem has been reported on only two previous occasions. The pathogenesis of both conditions has remained unclear, although the Chiari type I malformation is most likely due to hypoplasia of the posterior fossa with subsequent extension of the cerebellum through the foramen magnum. NF1 is also associated with a variety of cerebral dysplasias. We present a patient with both of these dysplastic lesions whose Chiari malformation was asymptomatic. PMID- 8453841 TI - Effect of dexamethasone on leukocyte numbers and lymphocyte-blastogenic responses to mitogens in infants with bronchopulmonary dysplasia. PMID- 8453843 TI - Comparison of two kits for measuring ferritin in blood. AB - Ferritin concentrations in blood are a good indicator of iron stores and can be measured in plasma or serum with commercial kits. We have measured plasma ferritin content in infants ranging from 3 to 15 months of age. During the first three years of a four-year study, plasma samples drawn from these infants were shipped to Abbott Laboratories in Chicago and assayed using the Ferrizyme immunoassay technique (Abbott Laboratories, Chicago, Illinois). For the last year of the study, we analyzed the remaining samples in St. John's using the radioimmunoassay GammaDab125 I Kit (Baxter Travenol Diagnostics, Inc., Cambridge, Massachusetts). Both kit manufacturers report inter- and intra-assay variability of < or = 5%. Results for samples analyzed by the second method were higher than earlier results from infants of the same age with the same intakes of iron; thus, we decided to analyze subsequent samples with both kits. PMID- 8453844 TI - Third-degree burn following use of microwave-heated cryogel pack. AB - It is common nursing practice to apply warm soaks to an area where extravasation of intravenous (IV) fluid has occurred. Here we report an adverse outcome due to the use of a microwave-heated, commercially available hot-cold cryogel pack to treat an extravasation of IV fluid in a patient. PMID- 8453845 TI - Removal of nasal foreign bodies in children. AB - Among the foreign bodies most often found in children's nostrils are hair, beads, toy parts, paper wads, and food. Sometimes extraction of nasal foreign bodies can be difficult, especially if they are spherical. The classical presentation is a unilateral, persistent, foul-smelling, purulent, or bloody nasal discharge. Ulceration, dislodgement of the foreign body into the nasopharynx, and aspiration of the foreign body can complicate the problem. PMID- 8453846 TI - Primum non nocere? Valuing of the risk of drug toxicity in therapeutic decision making. PMID- 8453847 TI - Cations in the didanosine tablet reduce ciprofloxacin bioavailability. AB - The effect of the magnesium-aluminum cations contained in didanosine chewable tablets on ciprofloxacin pharmacokinetics was evaluated in 12 healthy volunteers. The study was designed as a randomized, balanced, open, two-period, two-treatment crossover trial with a 7-day washout period between treatments. In one phase, subjects received a single 750 mg ciprofloxacin tablet alone. In the didanosinecation regimen, subjects received two didanosine-placebo tablets every 12 hours for two doses. On day 2, they received two didanosine-placebo tablets immediately followed by a single 750 mg ciprofloxacin tablet. Serial blood samples were collected for 24 hours after administration of each ciprofloxacin dose. The average maximum concentration of ciprofloxacin alone was 3.38 +/- 0.63 (SD) micrograms/ml compared with 0.25 +/- 0.21 (SD) micrograms/ml when ciprofloxacin was administered with the didanosine placebo (p < 0.0001). The mean (+/- SD) area under the plasma drug concentration-time curve from time 0 to the last measurable concentration for ciprofloxacin alone was 15.50 +/- 2.69 micrograms.hr/ml compared with 0.26 +/- 0.21 micrograms.hr/ml when ciprofloxacin was coadministered with the didanosine-placebo (p < 0.0001). The mean time to maximum concentration of ciprofloxacin alone decreased from 1.56 +/- 0.62 to 0.75 +/- 0.38 hours with buffer administration (p = 0.0012). The simultaneous administration of ciprofloxacin and didanosine should be avoided. PMID- 8453848 TI - A potentially hazardous interaction between erythromycin and midazolam. AB - Interaction between erythromycin and midazolam was investigated in two double blind, randomized, crossover studies. In the first study, 12 healthy volunteers were given 500 mg erythromycin three times a day or placebo for 1 week. On the sixth day, the subjects ingested 15 mg midazolam. In the second study, midazolam (0.05 mg/kg) was given intravenously to six of the same subjects, after similar pretreatments. Plasma samples were collected, and psychomotor performance was measured. Erythromycin increased the area under the midazolam concentration-time curve after oral intake more than four times (p < 0.001) and reduced clearance of intravenously administered midazolam by 54% (p < 0.05). In psychomotor tests (e.g., saccadic eye movements), the interaction between erythromycin and orally administered midazolam was statistically significant (p < 0.05) from 15 minutes to 6 hours. Metabolism of both erythromycin and midazolam by the same cytochrome P450IIIA isozyme may explain the observed pharmacokinetic interaction. Prescription of midazolam for patients receiving erythromycin should be avoided or the dose of midazolam should be reduced by 50% to 75%. PMID- 8453849 TI - Measurement of in vivo microsomal epoxide hydrolase activity in white subjects. AB - An impairment or hereditary defect in microsomal epoxide hydrolase is considered a possible risk factor for drug and chemical toxicity. However, nothing is known about variability of in vivo epoxide hydrolase activity in humans. Our objectives were to develop and test a simple pharmacokinetic approach for measuring microsomal epoxide hydrolase activity in a population. After administration of carbamazepine-10,11-epoxide (100 mg), oral clearance showed a nearly linear relationship to the log (transdihydrodiol/epoxide) urine ratio in the 24- to 36 hour interval (log metabolic ratio). Intrasubject variability was assessed by administering the epoxide twice to 13 subjects (1- to 4-month interval); the log metabolic ratio did not change significantly (mean difference, 11%; paired t test, p = 0.79). In 110 healthy white adults, the log metabolic ratio ranged from 1.28 to 2.05 (mean +/- SD, 1.68 +/- 0.155). Outliers indicating enzyme-deficient phenotypes were not observed, and the frequency distribution was unimodal normal. The log metabolic ratio detected pronounced inhibition of epoxide hydrolase by valpromide (six subjects; median ratio, 0.91) and induction by phenobarbital/phenytoin (six subjects; median ratio, 2.42). We conclude that distribution of microsomal epoxide hydrolase activity in a study group can be measured pharmacokinetically by use of carbamazepine epoxide. PMID- 8453850 TI - Nicotine and cotinine elimination pharmacokinetics in smokers and nonsmokers. AB - Published research suggests that smokers metabolize nicotine and its major metabolite cotinine more rapidly than nonsmokers. To evaluate this possibility, we studied the disposition pharmacokinetics of intravenous deuterium-labeled nicotine in 11 smokers (administered 2.0 and 0.5 micrograms/kg/min x 30 minutes) and in 11 nonsmokers (0.5 micrograms/kg/min). Smokers did not metabolize nicotine more rapidly; the clearance of nicotine normalized for body weight was significantly slower in smokers than in nonsmokers. Cotinine elimination rates were similar in the two groups. The disposition pharmacokinetics of nicotine was similar for the low and high doses in the smokers, indicating that metabolism is dose-independent. Our findings argue against "metabolic tolerance" as a mechanism for the dose escalation observed in smokers after initiation of smoking. Our findings suggest that nicotine and cotinine kinetic parameters for smokers may be extrapolated to nonsmokers for estimating exposures to environmental tobacco smoke in nonsmokers. PMID- 8453851 TI - Pharmacokinetics of prednisolone transfer to breast milk. AB - Prednisolone transfer to breast milk was studied in three nursing women who required oral steroid therapy for asthma. Each patient received a 50 mg intravenous dose of prednisolone phosphate, and blood and breast milk were sampled for 6 hours. Concentrations of prednisolone in milk declined more rapidly than in serum but were similar to expected unbound serum concentrations, suggesting that exchange between unbound prednisolone in serum and breast milk is relatively rapid and bidirectional. Because an average of 0.025% (range, 0.010% to 0.049%) of the prednisolone dose was recovered in milk, prednisolone transfer to breast milk does not appear to pose a clinically significant risk to nursing infants. PMID- 8453852 TI - The transfer of cocaine and its metabolites across the term human placenta. AB - This study defines human placental transport of cocaine and its two minor, but pharmacologically active, metabolites--norcocaine and cocaethylene. The experimental system was the single, isolated perfused cotyledon of a normal term human placenta, and antipyrine served as a freely diffusible marker. Cocaine was transferred rapidly by the placenta at a rate about 80% that of antipyrine. The transfer had characteristics of passive transport consistent with the high lipid solubility of the drug. We found no evidence of significant placental metabolism of cocaine during its rapid placental transfer. Ethanol did not alter the cocaine transfer rate. Norcocaine and cocaethylene were equally as rapidly transferred. Thus the placenta is no barrier to the transfer of cocaine and its derivatives to the fetus. PMID- 8453853 TI - Influence of aging on the pharmacokinetics and pharmacodynamics of doxacurium. AB - Doxacurium (30 micrograms/kg) pharmacokinetics and pharmacodynamics were evaluated in nine elderly (age range, 70 to 83 years) and nine young (age range, 19 to 39 years) patients under nitrous oxide-isoflurane anesthesia. The force of contraction of the adductor pollicis was monitored and plasma samples were collected for an 8-hour period. In the elderly group, doxacurium elimination half life was prolonged (119.7 versus 75.9 minutes) and plasma clearance was significantly reduced (1.75 versus 2.54 ml/min/kg) without any change in volume of distribution. Onset (12.9 versus 8.9 minutes) and recovery times (113.4 versus 48.1 minutes) were longer in the elderly group. The equilibrium rate constant to the effect compartment (kco) was decreased in the elderly (0.039 versus 0.051 min 1), whereas the effect compartment concentration at 50% block was similar in both groups (44.7 versus 54.1 ng/ml). An age-related reduction in muscle blood flow may be responsible for the decrease in kco. The pharmacokinetic changes observed in the elderly are consistent with a decreased function in the organs of elimination. PMID- 8453854 TI - Thiopurine methyltransferase activity in a sample population of black subjects in Florida. AB - Thiopurine methyltransferase (TPMT), is an enzyme detected in the human red blood cell that catalyzes the S-methylation of thiopurine drugs and is known to exist as a genetic polymorphism in white subjects. Investigations in this laboratory of red blood cell TPMT showed interethnic differences also existed in North American black subjects. A sample group of black subjects in Florida had a mean activity of 8.64 +/- 3.47 U/ml red blood cells and an antimode of 6.5 units, which represented values significantly lower than those obtained for both the mean activity and the antimode in other populations. The findings of this study suggest the possibility that TPMT activity may be under genetic control in North American black subjects and that this ethnic group may be at greater risk of experiencing thiopurine-induced toxicity caused by the lower overall mean activity of the enzyme. PMID- 8453855 TI - Quinidine interaction with nifedipine and felodipine: pharmacokinetic and pharmacodynamic evaluation. AB - Conflicting findings suggest that serum quinidine concentrations may be decreased or increased by nifedipine. We performed a double-blind, placebo-controlled trial of Latin-square design. Twelve healthy men received 3 days of pretreatment with nifedipine prolonged action (20 mg twice a day) or felodipine extended release (10 mg every day), another dihydropyridine calcium antagonist, followed by coadministration of quinidine (400 mg). Quinidine pharmacokinetics were not changed by either dihydropyridine. However, 3-hydroxyquinidine area under the concentration-time curve (AUC) and 3-hydroxyquinidine/quinidine AUC ratio were decreased by felodipine, consistent with reduced metabolite formation. Heart rates and adverse events were higher with felodipine, demonstrating lack of bioequivalence with nifedipine. The QTc interval did not deviate from that expected for the observed quinidine concentration, suggesting the pharmacokinetics of active quinidine metabolites were not markedly altered among treatments. Quinidine disposition did not appear to be changed sufficiently to be clinically important by sustained-release nifedipine and felodipine. PMID- 8453856 TI - Effects of nifedipine on functional liver plasma flow in normal subjects and in patients with cirrhosis. AB - The short-term effects of nifedipine (10 mg administered sublingually) on functional liver plasma flow, measured by calculating the extrarenal clearance of sorbitol, were investigated in 12 normal volunteers and 40 patients with cirrhosis scored according to Child-Pugh classification. Nifedipine significantly increased functional liver plasma flow in healthy subjects (23%, p < 0.0001) and in patients with cirrhosis in the Child-Pugh class A group (19%, p < 0.001); in patients in the Child-Pugh class B group functional liver plasma flow was not modified, whereas in the patients in the Child-Pugh class C group it was significantly reduced (-7%, p < 0.02). The mean arterial pressure showed a significant reduction in all groups studied. According to the pathophysiologic meaning of functional liver plasma flow, it is suggested that nifedipine meets criteria for an ideal test substance to evaluate the functional reserve of the liver. Furthermore, when used with the Child-Pugh classification, its effect on functional liver plasma flow may be useful to improve the efficiency of the Child Pugh classification, in establishing the prognosis of patients with cirrhosis. PMID- 8453857 TI - Effects of norepinephrine on endothelium-dependent vasodilation of forearm resistance vessels. AB - BACKGROUND: Endothelium-dependent dilatation of forearm resistance vessels is attenuated in patients with heart failure. Activation of the sympathetic nervous system could cause this abnormality by way of vasoconstriction and chemical inactivation of nitric oxide. METHODS AND RESULTS: The effects of concurrent intra-arterial norepinephrine infusions (25, 50 and 100 ng/min) on forearm blood flow responses to equipotent doses of an endothelium-dependent vasodilator, methacholine (0.3 and 1.5 micrograms/min), and an endothelium-independent vasodilator, nitroprusside (1 and 5 micrograms/min), were studied in 12 normal subjects. Norepinephrine infusions increased the mean plasma norepinephrine from 255 pg/ml at baseline to 460, 629, and 1089 pg/ml, respectively. Basal forearm blood flow was reduced from 2.9 to 1.6 ml/min/100 ml of forearm volume at the highest dose (p < 0.01). The average response to the lowest dose of methacholine (4.5 ml/min/100 ml) was not significantly reduced by concurrent infusion of norepinephrine (4.4, 4.2, and 4.3 ml/min/100 ml, respectively), whereas the response to the higher dose of methacholine (8.9 ml/min/100 ml) tended to be lower (7.2, 6.7, and 7.4 ml/min/100 ml, respectively) but did not attain statistical significance. Methacholine induced vasodilation was not more sensitive to norepinephrine than nitroprusside responses. Lower body negative pressure (-20 mm Hg) also significantly reduced baseline forearm flow and increased plasma norepinephrine but did not effect either methacholine or nitroprusside induced vasodilation. CONCLUSION: Sympathetic stimulation induced by infusion of norepinephrine or lower body negative pressure is not a potent antagonist to endothelium-dependent vasodilation of the forearm vasculature. These data suggest that sympathetic activation does not completely explain the abnormal endothelium-dependent vasodilation seen in patients with heart failure. PMID- 8453858 TI - Bedtime insulin added to daytime sulfonylureas improves glycemic control in uncontrolled type II diabetes. AB - BACKGROUND: To evaluate the possible benefits of the addition of intermediate acting insulin administered at bedtime to therapy with daytime sulfonylureas in patients with non-insulin-dependent diabetes mellitus for whom maximal doses of oral hypoglycemic agents have not been successful. METHODS: Study subjects were 16 consecutive obese patients aged from 44 to 78 years (mean age, 62 years) with histories of non-insulin-dependent diabetes mellitus for a mean of 9 years. None of the subjects had been able to control their diabetes with maximal doses of oral hypoglycemic agents. All patients received 20 mg glipizide or 10 mg glyburide twice a day, as well as education about the American Diabetes Association diet. Neutral protamine Hagedorn (NPH) insulin was empirically added in doses from 0.1 to 0.2 units/kg given at bedtime. The dose was adjusted on the basis of fasting blood glucose levels. RESULTS: Mean fasting blood glucose decreased from 13.7 +/- 3.4 to 8.3 +/- 2.7 mmol/L at 3 months and 7.3 + 2.0 mmol/L at 1 year. Glycosylated hemoglobin decreased from 9.0% +/- 1.9% to 6.2% +2 1.16% at 3 months and 6.3% +/- 1.22% at 1 year. CONCLUSION: A late-night dose of NPH insulin was added to a regimen of daytime sulfonylureas in a group of obese patients with type II diabetes whose hyperglycemia was not controlled with maximal doses of oral hypoglycemic agents. This treatment proved to be beneficial and is a useful alternative to conventional insulin therapy in this group of patients. PMID- 8453859 TI - Concentration-controlled versus concentration-defined clinical trials. PMID- 8453860 TI - Update on the medical treatment of hypercalcemia of malignancy. AB - Recent information on the pathophysiology and treatment of hypercalcemia of malignancy is reviewed, and the roles of two new agents, gallium nitrate and pamidronate, are discussed. Current evidence suggests that parathyroid hormone related protein is the most important mediator of humoral hypercalcemia of malignancy. In patients with local osteolytic hypercalcemia, cytokines have been implicated as mediators. Effective treatment of hypercalcemia of malignancy may improve patients' quality of life, although an episode of hypercalcemia is a poor prognostic indicator for survival. Gallium nitrate is more effective than salmon calcitonin and possibly more effective than etidronate in the treatment of hypercalcemia of malignancy. The primary adverse effect of gallium nitrate is nephrotoxicity, and its use must be avoided in patients who have renal dysfunction or who are receiving nephrotoxic drugs. Pamidronate is more effective than etidronate in the treatment of hypercalcemia of malignancy and can be administered as a single i.v. dose. The adverse effects of pamidronate include mild fever, hypocalcemia, and hypophosphatemia. Compared with gallium nitrate, pamidronate offers a more convenient dosing regimen, is less frequently associated with nephrotoxicity, and is less expensive. Single i.v. doses of either pamidronate or plicamycin effectively lower serum calcium levels and are reasonable choices for maintenance therapy. Gallium nitrate and pamidronate may be slightly more effective than previously available agents for initial treatment of hypercalcemia. Pamidronate currently offers the best combination of effectiveness, ease of administration, and a low rate of adverse effects. PMID- 8453861 TI - Computer dosing program for the initiation of vancomycin therapy. AB - The predictive performance of a computer dosing program used for initiating vancomycin therapy was studied. Initial serum vancomycin concentrations in 31 adult patients receiving vancomycin were estimated by using a computer program (T.D.M.S.) incorporating a two-compartment open model. Sixty-two serum vancomycin concentrations at steady state (Css) were obtained before and after one-hour infusions and compared with estimated Css values. Bias and precision were evaluated by calculating median error (ME) and median absolute error (MAE), respectively. Population-based estimates of volume of distribution (V) and clearance (CL) were compared with those obtained by fitting each patient's data set by using Bayesian analysis (BA) and non-linear least-squares regression (NLLS). Median (mean +/- S.D.) bias and precision for peak Css were 7.7 (10.2 +/- 10.8) and 7.7 (10.6 +/- 10.5) mg/L, and for trough Css were 7.4 (7.7 +/- 7.6) and 7.4 (8.8 +/- 6.2) mg/L. The medians were significantly different from zero. Estimated median (mean +/- S.D.) V, CL, and half-life were 0.72 L/kg, 0.60 (0.67 +/- 0.21) mL/min/kg, and 11.59 (12.87 +/- 3.91) hours. Median (mean +/- S.D.) CL values determined by BA and NLLS were 0.86 (0.89 +/- 0.32) and 0.85 (0.92 +/- 0.34) mL/min/kg, respectively. Both CL values were significantly greater than the population-based estimate. However, median V values determined by BA and NLLS did not differ from the population-based estimate. A revised clearance model derived from Bayesian analysis of data for the first 21 patients was tested in the 10 other patients and appeared to improve the predictive performance of the a priori model.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8453862 TI - Cefepime pharmacokinetics in patients with acute cholecystitis undergoing cholecystectomy. PMID- 8453863 TI - Sodium imbalance in a patient receiving total parenteral nutrition. AB - A case of hyponatremia and then hypernatremia in a hospitalized patient receiving total parenteral nutrition (TPN) is described, and the etiologies, diagnoses, and treatments of hyponatremia and hypernatremia are reviewed. A 23-year-old man whose left leg had been amputated after a motorcycle accident required parenteral nutrition because of an ileus. After developing sepsis, he was given antimicrobials administered in standard dilutions of 5% dextrose injection, contributing 3 L of free water a day to his fluid intake. The patient subsequently became hyponatremic, and the sodium content of the TPN solution was increased to 140 meq/L. Multiple doses of furosemide and albumin were administered because of weight gain and edema of the lower extremity. After 14 days, all antimicrobial therapy was discontinued, and 2 days later the patient became hypernatremic. The sodium content of the TPN solution was decreased and then eliminated. Because of a 16-kg weight loss, diuretic therapy was stopped. This patient's hyponatremia was caused by administration of large amounts of sodium-free fluids (i.e., antimicrobials in 5% dextrose injection). The most appropriate management would have been to change the fluids in which the antimicrobials were diluted, with no change in the sodium content of the TPN solution. The patient's subsequent hypernatremia is best explained by a loss of free water. To manage this condition, it would have been appropriate to administer 5% dextrose injection to replace the free-water loss. Once the patient had reached baseline weight and therapy with the diuretic had been discontinued, maintenance therapy with 0.45% sodium chloride injection would have been beneficial. No change in the TPN sodium content should have been required. It is important to recognize all factors that predispose patients receiving TPN to hyponatremia and hypernatremia. Although the focus is often on the sodium content of the TPN solution, sodium and fluid can be administered by other means, including medication admixtures and maintenance intravenous fluids. PMID- 8453864 TI - Criteria for use of patient-controlled analgesia in adults. PMID- 8453865 TI - Medroxyprogesterone acetate granted contraceptive indication in U.S. PMID- 8453866 TI - Amlodipine approved for hypertension, angina therapy. PMID- 8453867 TI - Breath-by-breath determination of inspiratory occlusion pressure. AB - In order to determine the influence of breath-by-breath measurement of inspiratory occlusion pressure (P0.1) on the pulmonary ventilation, the respiratory timing and the central inspiratory activity as reflected by P0.1 per se, nine healthy males were studied as they breathed in a valve assembly including an externally controlled occlusion valve. A new technique was used, terminating occlusions at a preset inspiratory threshold pressure and determining P0.1 from linear regression of the mouth pressure curve. Subjects were studied at rest and during light exercise, with the occluding function (threshold pressure) on or off during alternating periods. Breath-by-breath variability of P0.1 was of the order of 30%. We found no detectable influence of breath-by-breath short lasting inspiratory occlusions on tidal volume and ventilation. However, mean inspiratory flow was slightly increased due to a shortened inspiratory duration at rest and during light exercise. Also, raising the threshold pressure for occlusions from 69 to 147 Pa (0.7 to 1.5 cm H2O) resulted in a 20% increase of P0.1. We conclude that breath-by-breath measurement of P0.1 is a feasible technique, and that the slightly shortened inspiratory duration and the increased P0.1 with increased threshold pressure may not necessarily be expressions of a true stimulation of the central inspiratory activity. PMID- 8453868 TI - Plasma cholesterol ester transfer protein and distribution of cell cholesterol among plasma lipoproteins in vitro in distance runners and sedentary men. AB - Plasma cholesteryl ester transfer protein (CETP) activity and distribution of red blood cell (RBC) cholesterol among plasma lipoproteins during incubation of blood were determined in 14 distance runners and 10 sedentary men. Mean plasma CETP activity was similar in the runners (31% 10 microliters-1 18 h-1) and the sedentary men (32% 10 microliters-1 18 h-1). There was significantly (P < 0.05) greater accumulation of cell cholesterol in the HDL fraction (runners: 0.33 mmol l-1; sedentary men: 0.23 mmol l-1) which comprised a significantly (P < 0.05) larger proportion of the total amount of cell cholesterol lost to plasma (runners: 89%; sedentary men: 64%) in incubated blood from the runners. The results of this study suggest that in distance runners, high HDL concentrations are not accompanied by reduced plasma CETP levels but in conjunction with low triglyceride-rich lipoprotein levels in plasma, may promote preferential distribution of cell cholesterol into the 'antiatherogenic' HDL fraction. PMID- 8453869 TI - Regional differences of atrial natriuretic factors in humans. AB - During sinus coronarius catheterization in humans undergoing diagnostic right sided cardiac catheterization, levels of atrial natriuretic factor (ANF) measured in sinus coronarius (n = 12) were four times higher than in peripheral arterial blood. Atrial natriuretic factor underwent average extractions of 0.57, 0.40, and 0.28 in the kidneys (n = 14), liver (n = 15), and forearm (n = 15) respectively. However, a close relationship was observed between arterial and peripheral venous concentrations. The substantial clearance of ANF even over the forearm indicates that arterial sampling may be preferred in conditions with altered peripheral vascular resistance, since an uptake of ANF in the peripheral vascular bed is likely to have occurred. PMID- 8453870 TI - Right ventricular pressure-volume relations in chronic lung disease. AB - Thirty-four patients with chronic lung disease in stable condition were studied at supine rest (RS), at rest with the legs raised (LR), and during two levels of exercise: E1, 0 or 20 W, E2, 20 or 40 W. Five patients had normal spirometry (group 1), six patients had normal vital capacity but FEV1/VC below 70% (group 2), and 23 patients had VC below 95% of normal and FEV1/VC below 70% (group 3); group 3 was subdivided into group 3a (n = 14) without, and group 3b (n = 9) with a history of right heart failure (RHF). Right ventricular end-diastolic (RVEDV) and end-systolic (RVESV) volumes were computed from stroke volume and right ventricular ejection fraction (RVEF). RVEF at rest was correlated with lung function variables. Changes in RVEF from LR to E2 were normal, i.e. above 0.05, except for in group 3b, where RVEF did not increase with exercise. Relation between RVESV and pressure, and changes in stroke volume with RVEDV from LR to E2 were also abnormal in group 3b. These results show that in patients with chronic lung disease RVEF at rest reflects lung function, whereas its adaptation to exercise is impaired only in patients who have experienced RHF episodes. PMID- 8453871 TI - Circadian variation of cardiac autonomic regulation during 24-h bed rest. AB - We examined the effect of circadian variation on cardiac autonomic regulation in 11 young and middle-aged, healthy men during 24-h bed rest. Cardiac parasympathetic regulation expressed significant circadian variation: sensitivity of baroreceptor reflex, standard deviation of R-R intervals and the power of high frequency component of R-R interval variability (HFP) increased during the evening (2000-2100 h), were highest during the night (0200-0300 h), and gradually decreased again towards afternoon (1400-1500 h). Cardiac sympathetic regulation, the power of medium frequency component of R-R interval variability (MFP), did not show any significant circadian variation. The autonomic response to orthostatic stress changed after the 24-h bed rest; the sympathetic dominance in response to assuming upright position was before bed rest principally attributable to increased sympathetic activity (MFP increase), whereas after bed rest this was due to withdrawal of parasympathetic activity (HFP decrease). We conclude that the effect of circadian variation must be taken into account, while assessing cardiac autonomic regulation in patients with acute cardiovascular disorders. PMID- 8453872 TI - Effect of propofol and thiopentone on regional blood flow in brain and peripheral tissues during normoxia and hypoxia in the dog. AB - The effect of propofol and thiopentone on cerebral (CBF), myocardial (MBF), muscular, and arterial hepatic blood flow was assessed with radiolabelled microspheres in 12 chronically instrumented dogs, six given propofol and six thiopentone. Tissue blood flows were measured in the awake animal, after 30 min of normoxic anaesthesia (room air), and after 30 min of hypoxic anaesthesia using a mixture of 10% O2 and 3% CO2 in nitrogen. The decrease in CBF from awake to normoxic anaesthesia was similar with propofol and thiopentone (propofol: 77 +/- 8 to 38 +/- 3 ml min-1 100 g-1, P < 0.01; thiopentone: 66 +/- 3 to 33 +/- 2 ml min-1 100 g-1, P < 0.01). During hypoxia, CBF rose moderately in the two groups (respectively +19% and +28%, P < 0.05). The MBF increased in propofol and thiopentone groups after 30 min of anaesthesia with air (propofol: 97 +/- 23 to 137 +/- 15 ml min-1 100 g-1; thiopentone: 82 +/- 7 to 141 +/- 10 ml min-1 100 g 1) and increased still more during hypoxia. The increase in MBF was related to an increase in heart rate and blood pressure. The quadriceps blood flow decreased during anaesthesia in normoxia and in hypoxia. The diaphragmatic blood flow increased with thiopentone under hypoxia. The hepatic arterial blood flow was unchanged. It is concluded that the effects of propofol on regional blood flows are very similar to those of thiopentone. PMID- 8453873 TI - Chloroquine reduces blood pressure and forearm vascular resistance and increases forearm blood flow in healthy young adults. AB - The effects of chloroquine on resting blood pressure, forearm blood flow (FBF), and forearm vascular resistance (FVR) and on the responses to cold stimulation were studied in healthy young adults. Chloroquine sulphate (800 mg) reduced systolic pressure and increased FBF (P < 0.05) but had no effect on resting FVR. Cold immersion increased systolic pressure (from 108.8 +/- 1.7 mmHg to 127.8 +/- 6.9 mmHg; P < 0.05) diastolic pressure (from 73.4 +/- 2.7 to 95.2 +/- 6.2 mmHg; P < 0.01) and FVR (from 5.9 +/- 0.9 to 13.0 +/- 1.9 a.u.; P < 0.001) but reduced FBF (from 14.3 +/- 1.64 to 10.1 +/- 1.29 ml min-1; P < 0.05). Chloroquine reduced the increase in FVR reduced by cold stimulation (P < 0.01), but had little effect on the BF and FBF responses to cold stimulation. The hypotensive effect of chloroquine could be attributed, at least in part, to the observed fall in vascular resistance. PMID- 8453874 TI - Continuous quality improvement and the acute myocardial infarction patient. AB - Optimal outcomes for the AMI patient can be achieved by national and local healthcare organizations working together for quality care (see Figure). The JCAHO has provided hospitals with the 10-step process to guide quality improvement through a multidisciplinary, collaborative approach for planning and evaluating care. The ACC and AHA have established national standards for AMI care that can be used as guidelines for writing individual hospital AMI standards. The National AMI Registry Report provides current care statistics to participating hospitals. Hospitals can use the CQI dynamics to process the statistics to ensure that standards are met, ultimately facilitating clinical excellence along with cost-effective healthcare for patients with AMI. When caregivers take action to improve patient care based on these statistics, the time spent on data collection and evaluation will finally be worthwhile. PMID- 8453875 TI - Is 'The Great White Lie' a lie? Yes, no and maybe. PMID- 8453876 TI - Knowledge is not power. PMID- 8453877 TI - Visions of health care. PMID- 8453878 TI - Systems of ethics: a perspective. PMID- 8453879 TI - Ask the experts. PMID- 8453880 TI - Implementing changes in standards of care for patients with unstable angina: Wellens' syndrome. PMID- 8453881 TI - Temporary epicardial pacing in the postoperative cardiac surgical patient. PMID- 8453882 TI - From emergent transvenous pacemaker to permanent implant and follow-up. PMID- 8453883 TI - Radiofrequency ablation of a left-sided free-wall accessory pathway: a case study. PMID- 8453884 TI - Information about dual-earner families: is it essential to neonatal and pediatric critical care nurses? PMID- 8453885 TI - What criteria should be used for pet therapy in critical care? Are you aware of any hospitals doing this? PMID- 8453886 TI - Sleep protocol: a research-based practice change. PMID- 8453887 TI - Speaking the language of nursing diagnosis. Interview by Michael Villaire. PMID- 8453888 TI - The Basic Knowledge Assessment Tool (BKAT) for critical care nursing: its use and effect on orientation programs. AB - Findings from this study of 54 subjects who used the BKAT-3 in their professional practice indicate that it is being used most frequently in orientation programs conducted in critical care units, and that content and scores of the BKAT have resulted in changes in those programs. Scores are also being used for placement of nurses with previous critical care experience. In addition, findings from this study and from the literature indicate that research continues to be conducted using scores on the BKAT as a dependent variable, and that moderate to moderately high correlations exist between intended and actual use of the BKAT. PMID- 8453889 TI - Hemolytic-uremic syndrome. AB - HUS is one of the most common causes of acute renal failure in childhood. D+ HUS is the most common form and usually follows an episode of hemorrhagic colitis due to VTEC or S. dysenteriae type 1. The SLT elaborated by these organisms is responsible for the endothelial damage that is the initial insult in the pathogenesis of the acute renal failure. Excellent supportive care is necessary to reduce the mortality and morbidity due to HUS. PMID- 8453890 TI - Pseudofolliculitis barbae associated with an unusual hair whorl. AB - Descriptions of hair direction in the literature have emphasized unusual patterns of the scalp and associated developmental brain defects. We present the case of a white patient with unilateral pseudofolliculitis barbae associated with a hair whorl in the inframandibular region. To our knowledge, this is the first reported case of pseudofolliculitis barbae associated with a hair whorl. PMID- 8453891 TI - Sweet's syndrome with an exogenous cause. AB - A sixty-six-year-old white man presented with a five-day history of painful erythematous papules, plaques, pustules, and hemorrhagic bullae on both hands. His history was remarkable for having prepared and pickled fifteen quarts of home grown jalapeno peppers several days before the eruption occurred. The light microscopic examination of sections of lesional skin stained with hematoxylin and eosin revealed pathologic findings characteristic of Sweet's syndrome. We report this case because of its unusual presentation and apparent exogenous cause. PMID- 8453892 TI - Asymptomatic penile lesions. AB - Lichen planus is a papulosquamous eruption of unknown cause that at times can involve only the glans penis and therefore be clinically confusing. We recently evaluated two middle-aged men with annular lichen planus on the glans penis who presented for evaluation of possible infectious/venereal disease. PMID- 8453893 TI - Enalapril-associated erythema and vasculitis. AB - Our pharmacologic armamentarium is expanding at a tremendous pace, and requires that we as clinicians maintain a certain level of knowledge of the drugs that we use, as well as their metabolism, and how they may function, both positively and negatively, in a given patient. Certain drugs, such as the angiotensin-converting enzyme inhibitors, interfere with the natural deactivation of certain vasoactive substances normally present in the body. Since many of these systems are functionally interrelated (eg, angiotensin-converting enzyme and kininase II), we may see cutaneous side effects when these drugs are administered. Enalapril is an angiotensin-converting enzyme inhibitor that promoted a cutaneous eruption in a patient with renal failure secondary to diabetes. We suspect that our patient's vasculitis and maculopapular erythema is included in a large number of polymorphic eruptions that can be seen with angiotensin-converting enzyme inhibitors, and review the operative pathogenetic mechanism. Many of these side effects are dose related, and can be controlled or eliminated by lowering the dosage of angiotensin-converting enzyme inhibitor, depending upon the clinical circumstances. PMID- 8453894 TI - Allergic contact dermatitis from musical instruments. PMID- 8453895 TI - Erythrodermic (exfoliative) psoriasis. AB - Erythrodermic (exfoliative) psoriasis represents a manifestation of psoriasis that is difficult to treat and requires the execution of consummate clinical skills. Careful analysis of precipitating factors may prevent recurrences. Systemic as well as topical therapy are essential for a favorable outcome. PMID- 8453896 TI - A dermatologic diary. Portrait of a practice. PMID- 8453897 TI - Erythromelanosis follicularis faciei et colli. PMID- 8453898 TI - Granulomatous reaction to collagen implant: light and electron microscopic observations. AB - A fifty-three-year-old woman noted bilateral linear confluent papules involving the nasolabial folds following injection of bovine collagen (Zyderm). On light microscopic examination the dermis contained epithelioid granulomas centered around the degenerated bovine collagen. Electron microscopic examination demonstrated the degraded collagen fibers, which could be easily differentiated from the native collagen. The patient's clinical findings, management, and the pathogenetic mechanisms of this entity are reviewed. PMID- 8453899 TI - Pseudopelade of Brocq is lichen planopilaris: report of four cases that support this nosology. AB - Four patients are presented with pseudopelade of Brocq whose symptoms also illustrate the spectrum of symptoms of lichen planus. The literature is reviewed and the clinical and histologic features of pseudopelade of Brocq and lichen planopilaris are described. The literature on pseudopelade of Brocq is confusing and outdated. Since Degos's article in 1954, it has become commonly accepted that pseudopelade of Brocq is a nonspecific cicatricial end stage of scalp diseases resulting in alopecia. We maintain instead that pseudopelade of Brocq and lichen planopilaris are basically the same condition, namely a manifestation of lichen planus. PMID- 8453900 TI - [Superselective kidney artery embolization as therapy of choice in bleeding of benign origin]. AB - Over a period of 15 years selective embolization of the renal artery was performed in 22 patients (15 men, 7 women; mean age 47.5 [5-73] years), using a percutaneously introduced coaxial technique with a 3F catheter. Tissue glue (N butyl-2-cyanoacrylate) was employed in 18 cases, spiral wire in two, detachable balloon in three and gel-foam in one case. The bleeding had been iatrogenic in 20 cases, in one it was the result of a traffic accident, while in another the bleeding was from an angioma. The procedure was successful at the first attempt in 21 patients, permanently arresting bleeding in 18. There were three complications, transitory and not requiring treatment in two. In one patient gel foam embolization went to a wrong site and a nephrectomy had to be performed.- This form of selective embolization is the treatment of choice in traumatic injury to a renal vessel. PMID- 8453901 TI - [Diagnostic significance of parathyroid hormone-related protein in tumor patients with hypercalcemia]. AB - The clinical utility of measuring parathormone-related protein (PTHrP) was investigated in 94 patients (48 men, 46 women, mean age 56 [18-82] years) with tumour-associated hypercalcaemia, using a radioimmunoassay directed against the middle portion (53-84) of PTHrP (reference range < 5-21 pmol/l). Increased levels of the middle portion of PTHrP were found in 44 of the 73 patients (60%) with hypercalcaemia associated with solid tumours (median 49 [22-333] pmol/l). There was a positive correlation between the serum calcium concentration and the PTHrP (P = 0.018). The frequency of a raised PTHrP, indicating hormone-induced hypercalcaemia, was similar in patients with and without bone metastases (48% vs 66%). Elevated PTHrP was particularly frequent in patients with squamous cell carcinomas (17 out of 21; 81%), while PTHrP levels were normal in 18 out of the 21 patients with hypercalcaemia associated with haematological malignancies. PTHrP levels were normal in 37 out of 38 normocalcaemic tumour patients and in 30 out of 32 patients with primary hyperparathyroidism. Hypercalcaemia associated with benign disease was found in only one case, a female with marked benign breast hypertrophy.--The measurement of PTHrP allows the demonstration of a pathogenetic factor in tumour-associated hypercalcaemia, and differentiation from other causes of hypercalcaemia, in particular primary hyperparathyroidism. PMID- 8453902 TI - [Dramatic remission of a multiple metastasized melanoma caused by chemo immunotherapy]. AB - A 47 year old woman underwent excision of a malignant melanoma on the right shoulder. Nine years later she was attacked by intense pain in the back. Computed tomography, bone scans and immunohistochemical study of a liver biopsy specimen revealed metastases from the malignant melanoma in the liver, spleen and skeleton. Her Karnovsky score was 50%. Chemoimmunotherapy given for five cycles consisting of dacarbazine (800 mg/m2 body surface area every 4 weeks) together with ambulatory cytokine therapy (interferon alpha-2b subcutaneously, 5 million I.U. on days 1 and 3 to 7 in the first week, days 1, 3 and 5 in the second and third weeks and interleukin 2.9 million I.U. on days 1 to 5 in the second and third weeks; no treatment was given in the fourth week) raised the Karnovsky score to 90% and abolished the pain. Lactate dehydrogenase activity, originally 3372 U/l, dropped to normal. Computed tomography demonstrated definite shrinkage of the liver metastases and some regression of the splenic and bony deposits. This improvement has now been maintained for a total of eight cycles of therapy. PMID- 8453903 TI - [Influence of physical exertion on the hemostasis system. Assessment with sensitive biochemical markers]. PMID- 8453904 TI - [Clinical trials of drugs in university hospitals. Legal aspects]. PMID- 8453905 TI - [Myocardial infarct: anticoagulation and thrombolysis]. PMID- 8453906 TI - [Pericardial effusion following radiotherapy]. PMID- 8453907 TI - [Support collar in distortion of the cervical vertebrae]. PMID- 8453908 TI - [Kasabach-Merritt syndrome. Intraoperative heparin therapy with follow-up combination therapy of heparin and ticlopidine for the control of intravascular coagulation]. AB - A 39-year-old woman with Kasabach-Merritt syndrome (cavernous vascular malformations with disseminated intravascular coagulation) sustained a displaced fracture of the femoral shaft. Despite pronounced hypofibrinogenemia (< 0.1 g/l) there was no significant bleeding. The concentration of D dimer was raised to > 32 < 64 mg/l and that of prothrombin fragments F1 and F2 to > 10 nmol/l. The platelet count was 102,000/microliters and other coagulation parameters were normal or only slightly abnormal. The consumption coagulopathy was successfully controlled by continuous intravenous infusion of heparin (17,000 I.U./d) without need for clotting factor replacement, and was subsequently stabilized by combined treatment with low molecular weight heparin (5,000 I.U./d s.c.) and ticlopidine (250 mg twice daily by mouth). Oral therapy with acetylsalicylic acid alone or in combination with ticlopidine proved insufficient, being rapidly followed by a renewed fall in fibrinogen level and platelet count. The findings suggest that fibrin formation in the abnormal vascular territories was the principal pathogenetic factor in this case. PMID- 8453909 TI - [Spontaneous rupture of the left hepatic duct]. AB - A previously well 24-year-old man complained of persistent epigastric pain after a session of intensive muscle building exercise especially of the abdominal muscles. The abdomen was diffusely tender without guarding. There was an increased concentration of bilirubin (64.7 mumol/l), GOT (117 U/l), GPT (529 U/l) and alkaline phosphatase (150 U/l). Ultrasound examination showed a widening of the choledochal duct to 11 mm without signs of gallstones. Endoscopic retrograde cholangiography additionally revealed contrast-medium extravasation from the left hepatic duct. Computed tomography, performed immediately afterwards, confirmed the extravasation, while liver and pancreas were unremarkable. Laparoscopy revealed a 5 mm tear in the left hepatic duct, close to the hepatic duct bifurcation with bile effusion into the peritoneal cavity. The latter was rinsed endoscopically with Ringer's solution and drains were placed in the omental bursa and subhepatically in the region of the bile leak. To relax the sphincter Oddi glycerol trinitrate was administered postoperatively, for the first five days 72 mg/24 h intravenously, then for nine days twice daily 20 mg by month. No more bile drained as early as the second postoperative day and the patient was free of symptoms 2 weeks later. PMID- 8453910 TI - [Resistance to diuretics in congestive heart insufficiency]. PMID- 8453911 TI - [Institutional cost reimbursement by medical director's past contracts according to the health structure regulation of 1993]. PMID- 8453912 TI - [Mercury burden in amalgam fillings]. PMID- 8453913 TI - [Acute mountain sickness and high altitude pulmonary edema]. PMID- 8453914 TI - [Cold agglutinins in mycoplasma pneumonia]. PMID- 8453915 TI - [Current guidelines for cardiopulmonary resuscitation in the USA]. PMID- 8453916 TI - [Early polyneuropathy with severe symptoms in type I diabetes]. PMID- 8453917 TI - Tumor staging in gastroenterology. A rational approach to the application of endoscopy and radiology. PMID- 8453918 TI - Radiological diagnosis and preoperative staging of oesophageal malignancies. PMID- 8453919 TI - Role of endoscopy in the staging of colorectal carcinoma. PMID- 8453920 TI - Value of radiological techniques in the diagnosis and staging of colorectal carcinoma. PMID- 8453921 TI - Colorectal carcinoma: impact of staging on surgical treatment. PMID- 8453922 TI - Staging of esophageal carcinoma by endoscopy. PMID- 8453923 TI - Esophageal carcinoma: impact of staging on treatment. PMID- 8453924 TI - Staging of gastric cancer by endoscopy. PMID- 8453925 TI - Role of radiology in the diagnosis and staging of gastric malignancy. PMID- 8453926 TI - Impact of staging on treatment of gastric carcinoma. PMID- 8453927 TI - Staging of pancreatic and ampullary cancer by endoscopy. PMID- 8453928 TI - Pancreatic and ampullary carcinoma. Ultrasound, computed tomography, magnetic resonance imaging and angiography. AB - Ultrasound remains the most readily available and least expensive of the imaging techniques used in assessment of the upper abdomen. Ultrasound is very useful in the detection of pancreatic tumors as well as in the evaluation of the extent of the disease. If ultrasound fails technically or is inconclusive, CT is recommended. Determination of CA 19-9 may help to decide whether ultrasound should be followed by CT or other examinations (51). Patients with any equivocal or inconclusive abnormality on ultrasound or CT should undergo ERCP. Even when ultrasound and CT of the pancreas appear normal there may be an indication for performing ERCP if the clinical suspicion of pancreatic cancer is still strong (52). Angiography is a reliable method of assessing major vascular tumor involvement, which to most surgeons would be a sign of unresectability. Although for some investigators CT is superior to angiography in assessing vascular involvement, angiography is performed preoperatively in many cases because it delineates the vascular anatomy, which can be abnormal in up to one third of patients. Percutaneous biopsy is an important technique for confirming the radiologic diagnosis of unresectable pancreatic carcinoma, particularly for differentiating pancreas carcinoma from other focal pancreatic lesions such as islet cell tumor, lymphoma, and chronic pancreatitis. PMID- 8453929 TI - Effect of experimental limbic epilepsy on the estrus cycle and reproductive success in rats. AB - Epilepsy was induced in female rats by the injection of tetanus toxin (5 mouse LD50) unilaterally into the ventral hippocampus under anesthesia. During the 2-4 weeks that the rats exhibited intermittent spontaneous convulsions, daily vaginal smear tests showed that their estrous cycle was interrupted. In control rats such interruption only occurred for just a few days after the operation. Investigation of mating behavior, on the first night of proestrus, which occurred after 7 weeks from the operation, showed that there were fewer mounts, intromissions or ejaculations from the males, which were caged with previously epileptic animals. These females produced slightly smaller litters than their controls and there was a marked failure of their young to thrive in comparison with those of the control females. This failure appeared to be related to relatively high "stress" levels in the general laboratory environment. The impairment of reproductive success only lasted about 3 months after the original induction of epilepsy since subsequent litters to the same animals thrived normally. PMID- 8453930 TI - Comparison of 5 alpha-pregnan-3 alpha-ol-20-one and phenobarbital on cortical synaptic activation and inhibition studied in vitro. AB - The effects of 5 alpha-pregnan-3 alpha-ol-20-one (3 alpha-OH-DHP) and phenobarbital (PB) on synaptic excitation and inhibition in rat hippocampal slices in vitro were compared. Stimulations were made orthodromically and antidromically while we recorded extracellularly from the dendritic and the somatic layer of the CA1 region. Perfusion with 5 micrograms/ml of 3 alpha-OH-DHP for 30 min significantly increased the recurrent inhibition evoked by antidromic stimulation. The effect was most pronounced at short interstimulus intervals. The duration of the recurrent inhibition also was prolonged. There was no effect on the conditioned population spike after orthodromic paired-pulse stimulation. Furthermore, no effect was observed on the amplitude of the orthodromic fiber volley, the rate of increase in the field excitatory postsynaptic potential (EPSP) and the latency and amplitude of the CA1 population spike. Qualitative and quantitative similar findings were observed during perfusion with PB 0.1 mg/ml, (i.e., a concentration 20 times higher than that of 3 alpha-OH-DHP). Higher concentrations of PB also affected synaptic excitation. The findings suggest a similar effect of 3 alpha-OH-DHP and PB on recurrent GABA-ergic inhibition; however, 3 alpha-OH-DHP appears to be much more potent. PMID- 8453931 TI - Correlation of unit recordings with regional cell counts in epileptogenic human temporal lobe. AB - The previously reported diminished incidence of neuronal activity recorded from areas ipsilateral to a seizure focus may result from either cell loss or pathophysiologic changes in hippocampus and related structures. We examined records of single-cell discharge from 471 electrode bundles in 62 patients who later had cell counts taken from samples of resected tissue. Analysis of variance showed that amygdala and parahippocampal gyrus had more activity than hippocampus and the subicular complex and that the resected side had less activity overall. Only the posterior subicular complex showed more high-amplitude (> 50 microV) activity on the epileptogenic side; all other areas showed more activity contralaterally. Activity between 25 and 50 microV did not differ across sides or structures. Percentage of maximal cell count was correlated with the number of electrodes with high-amplitude activity only in the subicular complex. Low amplitude activity in nonresected hippocampus, however, was strongly negatively correlated with cell counts on the resected side, perhaps owing to compensatory mechanisms. Cell counts in hippocampus correlated negatively with high-amplitude unit activity in resected amygdala, suggesting reciprocity between these areas. These results suggest that the amount of cell activity recorded from mesiotemporal structures involves bilateral factors more complex than simple cell loss. PMID- 8453932 TI - Surgical treatment of children with medically intractable frontal or temporal lobe epilepsy: results and highlights of 40 years' experience. AB - Etiologic, pathologic, and clinical features of possible prognostic significance were studied in 118 children who underwent frontal or temporal lobe epilepsy surgery at the Montreal Neurological Institute (MNI) between 1940 and 1980 (excluding tumor cases). Mean age of seizure onset was 5.1 years (range 0-12 years), mean age at operation was 11.7 years (range 0.6-15 years), and median duration of follow-up was 15 years (range 2-31 years). Thirteen of 45 frontal surgery patients and 43 of 73 temporal surgery patients had an excellent outcome. In the frontal surgery group, this was restricted almost entirely to patients with an established etiology, particularly if this included a circumscribed resectable structural abnormality. In the temporal surgery group, a history of early, prolonged febrile seizures was usually associated with good outcome, unless there was additional evidence of extratemporal epilepsy. In the entire series, the presence of a nonresectable structural lesion or secondarily generalized seizures was associated with a poor outcome. PMID- 8453933 TI - Psychosocial consequences of postoperative seizure relief. AB - To address the question of whether complete seizure relief has a positive effect on psychosocial functioning in patients with temporal lobe epilepsy, a follow-up study was conducted at the Montreal Neurological Institute. The approach was one of "before-after" study, with focus on the successfully operated patients, those in whom complete seizure relief was obtained. The Washington Psychosocial Seizure Inventory, specifically developed and validated for use with epilepsy patients, was used for psychosocial assessments. Of 30 surgically treated patients screened for the study, 15 gained complete relief from seizures. At 1-year postoperative follow-up, they showed reductions in their problems scores on all but one of eight psychosocial scales; the average reduction ranged from 24% in Vocational Adjustment to 60% in Adjustment to Seizures. In the areas of Emotional Adjustment and Interpersonal Adjustment reductions were 37 and 48%, respectively. Among the component items, improvement was greatest in ability to concentrate and make decisions, confidence in interpersonal skills, ability to express personal opinions, and perception by others. No appreciable changes occurred in the 15 patients who did not gain complete relief of seizures; indeed, on six of the eight scales they showed a modest increase in their problem scores. This study provides evidence that complete relief from seizures leads to appreciable improvements in psychosocial well-being, manifest as early as 1-year postoperatively, in young adult patients. PMID- 8453934 TI - Electroencephalographic and magnetic resonance correlations in children with intractable seizures of Lennox-Gastaut syndrome and epilepsia partialis continua. AB - A study was performed of EEG-magnetic resonance imaging (MRI) abnormalities in 7 Lennox-Gastaut syndrome (LGS) children and 3 epilepsia partialis continua (EPC) children with intractable generalized and partial motor seizures, respectively. In 4 children with LGS and 3 children with EPC, depth electrodes were implanted in the centromedian thalamic nuclei (CM) for seizure control. In all children with LGS, hyperdense, T2-weighted MRI signals were observed at the mesencephalic level of the brainstem, whereas none of the 3 children with EPC had this finding. Patients with idiopathic LGS without cerebral hemisphere MRI abnormalities showed generalized bilateral and symmetrical spike-wave EEG activity. Patients with symptomatic LGS with unilateral hemispheric MRI abnormalities demonstrated asymmetrical EEG activity with higher amplitude spike-and-wave over the normal hemisphere. Patients with EPC with unilateral hemispheric lesions had lateralized higher amplitude spike-wave over the damaged hemisphere. These data suggest that abnormal mesencephalic MRIs are a sign of bad prognosis in patients with LGS but not with EPC. Maximal amplitude paroxysmal EEG activities may indicate the abnormal hemisphere in patients with EPC or the normal hemisphere in those with LGS. PMID- 8453935 TI - Midline spikes: is it another benign EEG pattern of childhood? AB - Clinical and electrographic features were retrospectively studied in 57 patients with midline (Fz, Cz, Pz) spikes as the only epileptiform activity in their EEG to determine possible predictors of outcome. Our study confirmed previous reports of early age of onset, activation by sleep, and Cz as the most frequent spike location. In contrast to previous studies with smaller numbers of patients, midline spikes were more common in males and most often associated with partial complex seizures and were not activated by sleep at an older age. Of the 29 patients who were followed for 6 months to 9 years, only 15 (52%) achieved good seizure control. Although a tendency toward a poor outcome was noted with several independent variables (positive family history of epilepsy, later age of seizure onset, abnormal EEG background activities, abnormal neuroimaging, abnormal neurologic examination), none was of statistical significance. This study suggests that epilepsy with midline spikes is not necessarily benign and that future studies with larger patient groups may be necessary to identify factors that influence prognosis. PMID- 8453936 TI - Reassessment of the clinical significance of periodic lateralized epileptiform discharges in pediatric patients. AB - A review of clinical data from 18 pediatric patients with periodic lateralized epileptiform discharges and bilateral independent periodic lateralized epileptiform discharges (PLEDs and BIPLEDs) showed 2 with chronic neurologic illness, 6 with a history of prior seizures, 14 with depressed sensorium at the time of EEG, 5 deaths, and 8 of 13 survivors with neurologic deficits. These findings are similar to the combined data from reports involving adult patients only. Separating pediatric patients with PLEDs from those with BIPLEDs shows some influence from patients with BIPLEDs. Overall, our data do not suggest significant clinical differences for PLEDs between children and adults. PMID- 8453937 TI - Defining the role of structural lesions and metabolic abnormalities in periodic lateralized epileptiform discharges. AB - We reviewed the EEG, clinical manifestations, computed tomography (CT) and magnetic resonance imaging (MRI) scans of 39 patients with periodic lateralized epileptiform discharges (PLEDs) or bilateral periodic lateralized epileptiform discharges (BIPLEDs) to determine the role of structural lesions (SL) and metabolic abnormalities (MA) in their pathogenesis. Thirty-eight patients had CT and 7 had MRI scans. Thirty-eight had lesions on CT or MRI. All those with PLEDs consistently had lesions on the side of the discharges, and 5 of 6 with BIPLEDs had lesions on both hemispheres. A subgroup of 23 patients with metabolic determination within 24 h of EEG all showed mild to moderate MA. They all also had SL. These findings support a primary role for SL but cannot exclude an additional role for MA. PMID- 8453938 TI - Ictal and interictal electrographic seizure durations in preterm and term neonates. AB - The effect of gestational age on neonatal ictal and interictal durations has not been investigated. Sixty-eight neonates with 644 electrographic seizures were identified retrospectively. Thirty-five full-term (FT) neonates were compared with 33 preterm (PT) neonates. Eighteen older preterm infants (OPT) [> 31 weeks estimated gestational age (EGA)] were also compared with 15 young preterm infants (YPT) of < or = 31 weeks EGA. Ictal/interictal durations were calculated for the total cohort with and without status epilepticus (SE). Statistical analyses were two-tailed t tests, chi-square calculations, and one-way analysis of variance (ANOVA) with Duncan's multiple-range test. Eleven of 35 (33%) FT had SE as compared with 3 of 33 (9%) PT (chi-square = 7.8, p < 0.05). The mean ictal duration was 14.2 min for FT infants as compared with 3.1 min for PT infants (p < 0.01); only borderline differences were noted after those with SE were excluded. Interictal durations were longer for OPT than YPT (p < 0.05). By ANOVA and Duncan's multiple-range tests, group differences included longer mean ictal durations for FT infants as compared with OPT infants (p = 0.06, ANOVA; p < 0.05, Duncan's), and longer mean interictal durations for FT infants versus OPT and OPT versus YPT (p = 0.02, ANOVA; p < 0.05, Duncan's). More developed neuronal networks result in longer ictal durations in FT than in PT neonates, including FT infants with SE.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8453939 TI - Unusual form of seizures induced by eye closure. AB - Seizures induced by eye closure are a rare but well-recognized form of reflex epilepsy. Two types have been reported: those induced by movement of the eyelids and those caused by lack of visual input. The EEG pattern is typically that of spike and wave discharges, either isolated to the occipital regions or greatest there. We report the case of a 19-year-old woman with a previously undescribed form of seizures induced by eye closure in whom both the physical act of eye closure and total lack of visual input were required for induction of a seizure. Both the EEG pattern of paroxysmal high-amplitude generalized beta activity and poor response to medication were different from what has been previously noted in patients with seizures induced by eye closure. We believe that a third form of seizures induced by eye closure exists and that its prognosis may be significantly worse than that of previously reported forms. PMID- 8453940 TI - Differential diagnosis in pseudoepileptic seizures. AB - With increasing use of intensive video-EEG monitoring, publications concerning pseudoepileptic seizures have burgeoned, but without clarification concerning differing psychopathologic mechanisms and without distinction of different syndromic varieties. The frequent concurrence of pseudoepileptic and epileptic seizures has not been sufficiently recognized, and an undue reliance on clinical experience on the one hand and individual tests such as EEG on the other has proven equally misleading in this group of cases. PMID- 8453941 TI - Vagus nerve stimulation has no effect on awake EEG rhythms in humans. AB - Vagus nerve stimulation (VNS) has been shown to have an anticonvulsant effect in several animal models, and clinical trials in patients were recently started. Experimental data have suggested that VNS may act by modulating EEG rhythmic activity. We studied the acute effects of VNS on EEG background rhythms in patients undergoing treatment for poorly controlled partial seizures. Six patients had recordings of satisfactory quality for quantitative EEG analysis. A significant effect of VNS on EEG total power, median frequency, or power in any of the conventional frequency bands, could not be demonstrated. Intraindividual analysis did not show a significant effect of VNS on total power for any patient, including those with apparent clinical response. We conclude that VNS at the parameters in current clinical use does not alter awake EEG background rhythms. The mechanism mediating acute antiepileptic effect remains unknown. PMID- 8453942 TI - Stiripentol in atypical absence seizures in children: an open trial. AB - Stiripentol (STP) was added to the antiepileptic drug (AED) regimen of 10 patients with uncontrolled atypical absence seizures (more than one seizure a day). Seven boys and three girls aged 6-16 years participated in the study. Concomitant AEDs included various combinations of phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ), and valproate (VPA). Parents counted daily seizures over a 4-week baseline period before institution of STP, and in a 20-week period during STP therapy. To compensate for drug interactions, doses of other AEDs were adjusted during STP administration to keep serum levels close to levels of the baseline period. Maintenance doses of STP were 1,000-3,000 mg/day, giving serum levels of 4-22 micrograms/mL. All patients experienced a decrease in atypical absence seizures. Average decrease was 70% (range 5-95%). Side effects experienced by some patients were dose related and included anorexia, nausea, vomiting, and lethargy. In only 1 patient did an adverse effect (vomiting) require discontinuation of STP. We conclude that STP shows promise in treatment of atypical absence seizures in children, and further trials are warranted. PMID- 8453943 TI - Outcomes of add-on treatment with lamotrigine in partial epilepsy. AB - The need for new antiepileptic drugs (AEDs) and more sensitive methods of assessing their efficacy is well recognized. This study was designed to evaluate the efficacy and safety of lamotrigine (LTG), a potential new AED and to develop and test new outcome measures. A health-related quality of life (HRQL) model was developed which contains previously validated measures of anxiety, depression, happiness, overall mood, self-esteem, and mastery and a specifically designed seizure severity scale with patient- and caregiver-based components. This HRQL model was used in a randomized, placebo-controlled, double-blind, cross-over study of LTG in 81 patients with refractory partial seizures. Seizure frequency was the primary measure and seizure severity and the HRQL were secondary measures of efficacy. The reduction in seizure frequency with LTG, relative to placebo, was 29.7% [95% confidence interval (CI) 17.8%, 39.9%] for total seizure count, 33.4% (95% CI 14.8%, 47.9%) for complex partial seizures (CPS) and 20.3% (95% CI 0.3%, 36.2%) for secondarily generalized tonic-clonic seizures (GTCS). However, although 41 patients elected to continue with LTG, only 11 experienced at least 50% reduction in total seizures, indicating that other factors influenced their decision. The score with LTG, relative to placebo, was significantly lower for the ictal (p = 0.017) and caregivers (p = 0.035) subscales of the seizure severity scale and significantly higher for happiness (p = 0.003) and mastery (p = 0.003). Simple correlation and multiple-regression analyses indicate that the effects on seizure frequency, seizure severity, and psychological variables appear to be independent of each other. This study indicates that LTG is effective in reducing seizure frequency and has additional favorable effects on seizure severity, mood, and perceived internal control. Some of the scales used indicate the potential of secondary measures of efficacy to enhance the sensitivity of trials of new AEDs. PMID- 8453944 TI - Valproate (VPA) metabolites in various clinical conditions of probable VPA associated hepatotoxicity. AB - Of a cohort of 470 epileptic patients in whom valproate (VPA) serum metabolites had been measured, 170 subjects without symptoms or signs of hepatic side effects were chosen as a reference group to establish the usual metabolic pattern. A wide interindividual variation of VPA metabolite concentrations was noted. Infants receiving VPA monotherapy and comedication with other antiepileptic drugs (AEDs) showed lower concentrations of the potential hepatotoxin 4-ene-VPA than did older children. In 11 patients with early symptoms and signs of possible fatal VPA associated hepatotoxicity, the following spectrum of benign clinical conditions was observed: unusually severe side effect during initiation of VPA therapy (1 patient), high VPA dosage (2 patients), reversible impairment of coagulation with bleeding manifestations in association with a slight increase in transaminase levels (1 child), and reversible liver dysfunction associated with febrile illness (7 patients). Reversible or irreversible fulminant liver failure had occurred in 5 children. Three of the 4 children with a fatal outcome had massive lactic acidosis. In all patients with probable VPA-associated hepatotoxicity, some aspects of VPA metabolism differed distinctly from that of the reference group, but the inter-individual profile of metabolites varied considerably, even in the subgroup of 4 children who died. Impairment of VPA beta-oxidation and increase of metabolites of alternative metabolic pathways (omega- and omega 1 hydroxylation, dehydrogenation reactions) were the most frequent findings. Increased values of 2-n-propyl-4-pentenoic acid metabolite of VPA (4-ene-VPA), could be detected only in 1 of the 5 patients with fulminant liver failure and in one other child with a slight hepatic dysfunction, indicating that this VPA metabolite is not the decisive hepatotoxin or indicator of hepatotoxicity. Because we cannot distinguish between benign and life-threatening hepatic adverse reactions on the basis of VPA metabolites, all identified changes are considered secondary to an as-yet-unknown primary metabolic event. The most toxic compound could be VPA itself, which may unmask an inborn or an acquired metabolic defect in the processing of fatty acids. PMID- 8453945 TI - Neuroprotective effect of felbamate after kainic acid-induced status epilepticus. AB - Felbamate (FBM), a newly developed antiepileptic drug (AED), was previously shown to offer some neuroprotective effects against hypoxic injury in both in vivo and in vitro studies. We administered FBM (100 or 300 mg/kg) to 30-day-old rats 1 h after they received a convulsant dosage of kainic acid (KA). Animals were then tested at age 80 days in the water maze, open field, and handling tests. Seizure latency was then tested by flurothyl inhalation. Animals that received 300 mg/kg FBM performed better in all three tests and had longer latencies to flurothyl induced seizures than did animals that received vehicle. This study suggests that FBM may have some neuroprotective effects after KA-induced status epilepticus (SE). PMID- 8453946 TI - Interaction of felbamate with several other antiepileptic drugs against seizures induced by maximal electroshock in mice. AB - The anticonvulsant effects of felbamate (FBM) alone or in combination with phenytoin (PHT), carbamazepine (CBZ), valproate (VPA), or phenobarbital (PB) were investigated against maximal electroshock (MES) seizures in mice. Nonprotective doses of the prototype antiepileptic drugs (AEDs) enhanced the protective effects of FBM against electrically induced seizures, as shown by significant reduction of FBM ED50 values. Toxicity as determined by rotorod test was not significantly potentiated, however, and the protective index (PI = TD50/ED50) of FBM was increased by > 100% for each AED interaction. The increase in anticonvulsant potency of FBM after its combination with nonprotective doses of AEDs could not be accounted for by a pharmacokinetic mechanism. PMID- 8453947 TI - Influence of chronic aminophylline on the anticonvulsant efficacy of phenobarbital and valproate in mice. AB - The protective efficacy of phenobarbital (PB, 120 min before testing) and valproate (VPA, 30 min before testing) alone or combined with aminophylline (a single dose of 50 mg/kg, 3-day or 14-day administration twice daily 50 mg/kg at 8.00 a.m. and 8.00 p.m.) was evaluated against maximal electroshock-induced seizures (MES) in male mice. All drugs were given intraperitoneally (i.p.), and the protection provided by PB and VPA was evaluated as the respective ED50 value (in mg/kg). Aminophylline in a single dose of 50 mg/kg (30 min before electroconvulsions) distinctly reduced the protective efficacy of both PB and VPA, reflected by the increase in the respective ED50 values from 22 to 31 mg/kg (p < 0.001) for PB and from 247 to 281 mg/kg (p < 0.001) for VPA. After administration of aminophylline for 3 days (electroshock was performed 30 min after the last aminophylline injection), the respective ED50 values for PB and VPA were 29.5 (p < 0.01) and 269 mg/kg (p < 0.01 vs. saline-treated animals). Chronic treatment with aminophylline (14 days) resulted in further impairment of the protective activity of PB and VPA. Specifically, the ED50 value of PB was 39 mg/kg (p < 0.05 vs. PB+single injection of aminophylline) and that of VPA was 318 mg/kg (p < 0.01 vs VPA+single injection of aminophylline). Plasma levels of both PB and VPA were not affected by chronic aminophylline; moreover, the plasma level of theophylline was even lower after chronic aminophylline as compared with single aminophylline administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8453948 TI - The inferior colliculus of GEPRs contains greater numbers of cells that express glutamate decarboxylase (GAD67) mRNA. AB - Previous studies have shown significantly greater GABA levels and numbers of GABAergic neurons in the central nucleus of the inferior colliculus (ICCN) of genetically epilepsy-prone rats (GEPR-9s). In the present study, in situ hybridization and emulsion autoradiographic techniques were used to determine whether there are also elevated numbers of ICCN cells that contain the 67-kD form of mRNA for the GABA synthesizing enzyme, glutamate decarboxylase (GAD), in GEPR 9s as compared to normal Sprague-Dawley (SD) rats. Hybridization with a 35S labeled RNA probe complementary to a span of monkey GAD mRNA labeled cells throughout the brain including the ICCN. Labeled cells in the ICCN appeared to be of different sizes that corresponded with previous descriptions of GABAergic neurons from immunocytochemical studies. In the GEPR-9s, a larger number of GAD67 cRNA labeled neurons was observed in the ICCN as compared to SD rats. The external nucleus of the inferior colliculus was also found to contain significantly greater numbers of GAD67 cRNA labeled neurons whereas in the frontal cortex, a region of the brain that is not required for audiogenic seizure activity in GEPR-9s, there were no significant differences in hybridization between GEPR-9s and SD rats. Interestingly, within the superficial layers of the superior colliculus there was a higher density of hybridization in GEPR-9s than in SD rats indicating higher levels of GAD expression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8453949 TI - Reduced susceptibility to seizures in carbonic anhydrase II deficient mutant mice. AB - The seizure susceptibility of carbonic anhydrase II (CA) deficient mice and their normal littermates was determined and compared. In flurothyl-induced seizures, CA deficient mice displayed longer latencies to the onset of both clonic and tonic clonic seizures. In pentylenetetrazole-induced seizures mutant mice exhibited a lower incidence of clonic seizures than did their normal littermates. Acetazolamide (a CA blocker) was used for the pretreatment of normal mice to compare them to CA deficient littermates. The pretreated mice displayed a lower incidence of flurothyl-induced tonic-clonic seizures and of both types of pentylenetetrazole seizures. The attempts to elicit audiogenic seizure did not reveal any difference between normal and mutant littermates. However, when the mice were primed by a loud sound during the critical period and retested for audiogenic seizures again at age 1.5 months, the CA deficient mice displayed a significantly lower incidence of seizures. The similarity between the anticonvulsant action of CA deficiency and the anticonvulsant action of acetazolamide suggests an important role of CA in seizures. The exact mechanism of anticonvulsant action by CA inhibition, however, remains to be elucidated. PMID- 8453950 TI - Effect of arterial blood pressure and serum glucose on brain intracellular pH, cerebral and cortical blood flow during status epilepticus in the white New Zealand rabbit. AB - Generalized seizures can induce both hypertension and hyperglycemia which may aggravate preexisting cerebral or medical conditions in patients. In vivo fluorescent imaging of regional cortical blood flow and brain intracellular pH (pHi) was performed in fasted New Zealand rabbits (n = 35) in which either mean arterial blood pressure (MABP) or serum glucose was the covaried factor during pentylenetetrazole induced status epilepticus under 1.5% inspired halothane. Baseline brain pHi and regional cortical blood flow were 7.02 +/- 0.02 and 51.1 +/- 1.7 ml/100 g/min, respectively. Following seizure induction, MABP increased to 105 mm Hg and brain pHi fell to 6.79 +/- 0.03 within 15 min and remained at this level for 1 h (P < 0.001). With normalization of MABP during ongoing seizures, there was no worsening in brain pHi despite a significant decrease in regional cortical blood flow. Hyperglycemia decreased pHi to 6.71 +/- 0.02 compared to 6.84 +/- 0.04 in normoglycemic animals (P < 0.001). Using pHi as a cerebral metabolic index, these data suggest that normalization of MABP does not increase metabolic injury while hyperglycemia does significantly worsen brain acidosis. Therefore, administration of glucose to patients with status epilepticus should be avoided unless there is documented hypoglycemia. PMID- 8453951 TI - Compensatory function of central dopaminergic system for suppressing psychic seizures--repeated plasma homovanillic acid measurement in refractory temporal lobe epilepsy. AB - Repeatedly measured plasma homovanillic acid concentration, as a clinically available index of central dopaminergic activity in a patient with temporal lobe epilepsy during a drug-free period, was significantly correlated with seizure frequency in the week immediately following, but not preceding, blood sampling days. This result suggests a compensatory function of the dopaminergic system in suppressing refractory psychic seizures. PMID- 8453952 TI - Efficacy and safety of zonisamide: results of a multicenter study. AB - The safety and efficacy of zonisamide (ZNS), a new antiepileptic drug, was tested in 167 adult participants who entered a historical-controlled 16-week open label, multicenter study. The median percent reduction from baseline of partial seizures was 51.8% in the fourth month of the study (baseline median = 11.5 sz/month; treatment weeks 13-16 = 5.5 sz/month). Persons completing the efficacy study successfully were eligible for a long-term safety study; 113 entered this study. Adverse effects involved principally the CNS and were similar to those seen with other antiepileptic drugs. Four persons (3.7%) developed kidney stones and were withdrawn from the study 250-477 days after starting ZNS. Because of the high percentage of kidney stones, development of ZNS was stopped in the United States but was continued in Japan. PMID- 8453953 TI - Operative strategy in patients with MRI-identified dual pathology and temporal lobe epilepsy. AB - We performed a prospective study using preoperative magnetic resonance imaging to identify hippocampal formation atrophy in 15 consecutive patients with intractable partial epilepsy who had undergone a stereotactic resection of an extrahippocampal temporal lobe foreign-tissue lesion. A stereotactic lesionectomy was performed in all patients, i.e., only the imaging-defined lesion itself was resected. Hippocampal formation atrophy was identified in three of the 15 patients. Neuroimaging-detected hippocampal formation atrophy has been shown to be a reliable marker of moderate to severe mesial temporal sclerosis. All patients with hippocampal formation atrophy had an unfavorable operative outcome. Pathological examination of the hippocampus in one patient with neuroimaging identified hippocampal formation atrophy who subsequently received an anterior temporal lobectomy revealed mesial temporal sclerosis. Nine of the 12 patients without hippocampal formation atrophy experienced a significant reduction in seizure tendency after lesionectomy. The surgically excised hippocampus in one patient without hippocampal formation atrophy who later underwent a temporal lobectomy showed no significant neuronal loss. Results of this study have modified the surgical approach taken at this institution in patients with temporal lobe lesional epilepsy. Patients with magnetic resonance imaging-defined dual pathology now undergo a temporal lobectomy which includes resection of the hippocampus and the foreign-tissue lesion. PMID- 8453954 TI - Pharmacological dissociation of the motor and electrical aspects of convulsive status epilepticus induced by the cholinesterase inhibitor soman. AB - In an effort to validate methods to be used in a screen for drugs effective as anticonvulsants for soman-induced convulsions, scopolamine (0.2 mg/kg) or diazepam (1 mg/kg) were given (i.m.) to male guinea pigs as a pretreatment 30 min before a convulsant dose of soman. Pyridostigmine, atropine and pralidoxime chloride also were given to counteract the lethality of soman. All animals challenged with soman and which did not receive either diazepam or scopolamine exhibited convulsive status epilepticus (SE), identified by continuous electrographic seizure activity (EGSA) and continuous motor convulsions. Despite the presence of continuous motor convulsions in all animals pretreated with diazepam and challenged with soman, EGSA was not observed in five of the seven animals. Continuous motor convulsions developed in four of seven animals pretreated with scopolamine and challenged with soman, but EGSA was not observed in any scopolamine-pretreated guinea pig. Neuronal necrosis was observed in the hippocampus, thalamus, amygdala, and cerebral and pyriform cortices in each animal with EGSA, but not brain damage was found in subjects without EGSA. Thus, although convulsions, EGSA and brain damage normally occur together in animals exposed to soman, the convulsions can be pharmacologically dissociated from the EGSA and brain damage, demonstrating that the clinically manifested convulsions are not dependent on EGSA recorded from the cortex or on abnormal activity which leads to neuronal necrosis in the forebrain. PMID- 8453955 TI - Metformin for obese, insulin-treated diabetic patients: improvement in glycaemic control and reduction of metabolic risk factors. AB - The efficacy and safety of metformin in the treatment of obese, non-insulin dependent, diabetic subjects poorly controlled by insulin after secondary failure to respond to sulphonylureas has been investigated. Fifty insulin-treated, obese diabetics participated in this prospective, randomised double-blind six-month trial. After a four-week run-in period, during which all patients were given placebo (single-blind), patients were randomly assigned to continue to receive placebo or to active treatment with metformin. At six months, there was a relevant and significant improvement in glycaemic control in diabetics receiving the combined insulin-metformin treatment (decrease in glucose -4.1 mmol.l-1; glycosylated haemoglobin A1 decrease -1.84%). No significant changes were seen in diabetics receiving insulin and placebo. There was a significant decrease in blood lipids (trygliceride and cholesterol), an increase in HDL-cholesterol and a reduction in blood pressure in diabetics taking metformin. These positive findings were most marked in the 14 diabetics who experienced a good response to metformin (glucose profile < 10 mmol.l-1), and were less marked but still significant in the remaining 13 diabetics, whose response to therapy was not so good (glucose profile > 10 mmol.l-1). The fasting insulin level was significantly lower after six months of combined insulin-metformin treatment as shown by a 25% reduction in the daily dose of insulin (-21.6 U/day). Metformin was well tolerated by all diabetics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8453956 TI - Comparative effects of felodipine, nitrendipine and nifedipine in healthy subjects: concentration-effect relationships of racemic drugs and enantiomers. AB - The effects of racemic (rac) felodipine, rac-nitrendipine and nifedipine (all 20 mg solution p.o.) on non-invasively measured blood pressure and heart rate were investigated in a randomised, double-blind, cross-over study in 12 normotensive, young, healthy males. Compared to baseline values, heart rate increased more after rac-felodipine treatment (+47% at maximum) than rac-nitrendipine (+40%) and nifedipine (+38%); only small and variable changes in blood pressure were observed with any of the drugs. The baseline-corrected area under the heart rate time curve up to 4 h after the administration of rac-felodipine was 197% and 180% larger than after nifedipine and rac-nitrendipine treatment, respectively. The effects on heart rate could be fitted individually to a sigmoidal Emax-model without hysteresis for all drugs under investigation. The relative potencies of the unbound drugs for their indirect effects on heart rate were 1:7:43 for nifedipine, rac-nitrendipine and rac-felodipine, respectively. The active (S) enantiomers of felodipine and nitrendipine appeared to be 9- and 60-times as potent as nifedipine in this respect, assuming no (inter)activity of the (R) enantiomers. Individual and mean changes in blood pressure were small, they were not related to plasma concentrations, and did not differ between treatments. PMID- 8453957 TI - Serotonin-induced platelet aggregation predicts the antihypertensive response to serotonin receptor antagonists. AB - The 5-HT2-receptor antagonist ketanserin (20-40 mg b.i.d.) was administered to 62 patients of both sexes with uncomplicated primary hypertension. After 4 weeks of treatment about 50% of the patients had reached the target diastolic blood pressure of 90 mm Hg or below. Interindividual variability was large. In a retrospective analysis the variability could not be explained by sex or the dose of ketanserin. There was a weak association between age and systolic blood pressure response (r = 0.24; P = 0.06), which could be entirely accounted for by the higher base line blood pressure in the elderly patients. In one group of patients (n = 12), the ex vivo aggregation to serotonin (10(-6) M) was studied during treatment with placebo and ketanserin. Ketanserin completely inhibited 5 HT-induced aggregation in all patients. There was a close correlation between the area under the 5-HT-induced platelet aggregation curve during placebo and the subsequent reduction in diastolic blood pressure after 4 weeks of treatment with ketanserin. The present data suggest that the blood pressure response to ketanserin can be predicted from the ex vivo sensitivity of platelets to serotonin. By implication, they also support a role for serotonergic mechanisms in hypertension. PMID- 8453958 TI - Identification of factors regulating thiopurine methyltransferase activity in a Norwegian population. AB - Red blood cell (RBC) thiopurine methyltransferase (TPMT), an inactivating pathway of 6-mercaptopurine, is controlled by genetic polymorphism and is subject to ethnic variation. RBC TPMT is a good predictor of clinical outcome in children with acute lymphoblastic leukemia. RBC TPMT activity was determined in 226 patients, 176 of them living in northern Norway (of which 123 were Saami (Lapps)). Demographic variables, use of drugs and presence of chronic diseases were evaluated as possible predictors of RBC TPMT activity by a multiple regression model. Men had higher RBC TPMT activity compared to women. Living in the northernmost county of Norway was associated with increased RBC TPMT activity irrespective of ethnicity. The use of diuretics was associated with increased RBC TPMT activity. The gender difference in RBC TPMT activity may indicate a need to treat male subjects more aggressively with thiopurine drugs compared to female subjects. PMID- 8453959 TI - Evaluation of a new spacer device for drug inhalation. AB - We have studied the efficacy and acceptability of a new inhalation spacer device. The functional principle of the device, differing from that of conventional spacers, is based on evaporation of the propellant during circular movement of the aerosol in a small spherical chamber. We assessed the bronchodilating effect of salbutamol (Salbuvent) inhaled with the new spacer (Rondo) compared with salbutamol (Ventoline) inhaled with the spacer Volumatic and with salbutamol (Salbuvent) inhaled with a conventional metered dose actuator using a double blind cross-over arrangement. Fifteen asthmatic patients were treated over a period of 4 weeks. They used each of the three different devices for 2-3 days every week. Peak expiratory flow rates were recorded every morning after one and after two puffs of the study drugs. The bronchodilator responses to the three treatments were similar within narrow ranges of estimate. By visual analogue scale assessment the new spacer was significantly easier to handle (P < 0.05) and more convenient to carry around (P < 0.01) than Volumatic. PMID- 8453960 TI - Variation in the binding affinity of warfarin and phenprocoumon to human serum albumin in relation to surgery. AB - The binding equilibria of warfarin and phenprocoumon with defatted human serum albumin were studied by equilibrium dialysis in 33 mM sodium phosphate buffer, pH 7.4, 37 degrees C. The binding isotherms for both ligands were consistent with binding to two similar and independent sites in the albumin molecule. The binding affinity of warfarin was markedly increased on adding palmitic acid up to palmitate 4 mol per mol albumin and then it decreased. The binding affinity of phenprocoumon varied similarly but to a lesser degree. Serum samples were obtained from 14 patients undergoing knee joint surgery, six consecutive samples from each patient. The binding affinity of warfarin and phenprocoumon added in low concentrations to the serum samples was consistently less than to purified albumin. The binding affinity for warfarin increased slightly with increasing fatty acid concentrations during surgery, but the increase was much less than expected from the in vitro studies. The binding of phenprocoumon in the serum samples was not influenced by changing fatty acid concentration. The binding affinity for both drugs decreased markedly during the three days following surgery. PMID- 8453961 TI - Stereoselective pharmacokinetics of oral felodipine and nitrendipine in healthy subjects: correlation with nifedipine pharmacokinetics. AB - The pharmacokinetics of racemic (rac) felodipine, rac-nitrendipine and nifedipine (all given as an oral dose of 20 mg in solution) have been investigated in a randomised cross-over study in 12 healthy male subjects using stereoselective assays. Both felodipine and nitrendipine exhibited stereoselective pharmacokinetics. On average, the AUCs of the active (S)-enantiomers of felodipine and nitrendipine were 139% and 104% higher than those of their optical antipodes, but the elimination half-lives of the enantiomers of each racemate were not different. The AUCs of nifedipine, rac-felodipine, rac-nitrendipine and of their enantiomers were highly correlated (all r > 0.83), suggesting closely related rate limiting steps in the in vivo first-pass metabolism of these high clearance drugs. Stereoselectivity was only a minor contributor to inter individual variability in the oral pharmacokinetics of these compounds in healthy subjects. PMID- 8453962 TI - The effect of oxprenolol dosage time on its pharmacokinetics and haemodynamic effects during exercise in man. AB - We have studied the effect of dosage time of oxprenolol (Trasicor) on its pharmacokinetics and pharmacodynamics in six healthy volunteers. The drug effects measured were heart rate and systolic blood pressure during exercise. Oxprenolol was taken orally at 08.00 h, 14.00 h, 20.00 h, and 02.00 h in randomized order, with 1 week between successive doses. There were differences in the pharmacokinetics of oxprenolol for the ratio between the apparent volume of distribution and systemic availability (P = 0.04) and for elimination half-life (P = 0.006). Both were lowest after administration at 14.00 h (163 (77) l and 1.2 (0.6) h; mean (SD)) and highest after administration at 02.00 h (229 (100) l, and 1.7 (0.6) h). The systolic blood pressure during exercise before oxprenolol did not vary with dosage time, but heart rate during exercise before intake was lowest before dosage time 08.00 h and highest before dosage time 20.00 h (P = 0.03). The time-course of heart rate during exercise after oxprenolol was described by a model that incorporated the factors drug concentration and spontaneous diurnal variation. EC50 and Emax did not vary between dosage times. The spontaneous diurnal variation in heart rate during exercise was unaffected by oxprenolol, leading to an apparently greater effect of oxprenolol during the night than during the day. PMID- 8453963 TI - Pharmacodynamic model of the haemodynamic effects of pinacidil in normotensive volunteers. AB - The concentration-effect relationships of pinacidil, a peripheral vasodilator, have been measured in 12 healthy adults who received placebo or pinacidil 25 mg daily for 1 week in a cross-over experiment. Diastolic blood pressure (DBP) and heart rate (HR) were recorded and blood samples were taken on days 1 and 7. Plasma drug concentration-time data were fitted by a biexponential function with zero-order input. The pharmacokinetic model was incorporated into a combined pharmacokinetic-dynamic model (PK-PD) using the Hill equation, which has three parameters: n, the sigmoidicity parameter, Emax the maximum effect and EC50 the concentration which gives 50% of Emax. For delta DBP, the parameter medians were estimated as n = 5, EC50 = 44.6 ng.ml-1 and Emax = 13.5 mmHg. A hysteresis loop was found when delta HR was plotted against concentration, which could be fitted by a linear effect compartment model. Simulations showed that experimental delta DBP points on Day 7 could be predicted from a simulated curve computed by the model using parameters estimated on Day 1. Using the simulation, it was possible to suggest an optimal dosage regimen for pinacidil tablets. PMID- 8453964 TI - The effect of haemodialysis on the pharmacokinetics of perindoprilat after long term perindopril. AB - We have studied the pharmacokinetics of perindoprilat, the active metabolite of perindopril, in 7 hypertensive patients undergoing haemodialysis after short-term and long-term (1 month) perindopril. We also measured angiotensin-converting enzyme activity. Each subject took 2 mg of perindopril after a 4-hour haemodialysis. Serial blood samples were obtained each hour during dialysis and between dialysis (7 samples over 44 h). Perindoprilat steady state was reached within 5 haemodialysis sessions. There was a high degree of angiotensin converting enzyme inhibition after the first dose. Administration for 1 month did not modify the time to peak perindoprilat concentration but significantly increased the mean maximal concentration: 10.2 versus 26.8 ng.ml-1. The mean accumulation ratio was 3.5. The mean reduction in perindoprilat concentration after dialysis was greater than 50%. Perindoprilat haemodialysis clearance was 62 ml.min-1 after the first administration and 72 ml.min-1 after 1 month. Tolerance of perindopril was good throughout the study. Treatment can be begun with 2 mg of perindopril after haemodialysis in hypertensive patients undergoing haemodialysis. PMID- 8453965 TI - Steady-state pharmacokinetics of methadone in opioid addicts. AB - Kinetic parameters were investigated in tolerant methadone maintenance patients. The disposition of methadone at steady-state was assessed on 8 occasions-in 5 opioid addicts prescribed wide ranging doses of methadone (10 mg to 60 mg per day)-providing unique pharmacokinetic data. Statistical analysis showed that the kinetics of oral methadone at steady-state were described using a single compartment model. Analysis of the plasma concentration-time curves gave estimates of the variance of methadone clearance and apparent volume of distribution, and indicate that methadone is rapidly absorbed (mean Ka, 1.7 h-1) with a detectable increase in the plasma drug concentration 15 to 30 min after dosing. The elimination of methadone from plasma was found to occur slowly (mean t1/2 26.8 h) beginning soon after the administration of the daily oral prescription. The apparent volume of distribution-assuming the oral bioavailability (f) of methadone to be 0.95--was large (mean 6.7 l.kg-1). The slow clearance of this drug from the body (mean 3.1 ml.min-1.kg-1) confirms that daily dosing at steady-state is adequate to maintain effective plasma concentrations throughout the dosing interval. PMID- 8453966 TI - The relation between type of renal disease and renal drug clearance in children. AB - It is generally assumed that the renal clearance of drugs in patients with renal impairment are affected to a similar extent regardless of the type of renal disease (intact nephron hypothesis). We have studied the effect of underlying renal disease on the pharmacokinetics of cefotaxime and desacetylcefotaxime in two groups of children (ages 7 to 16 y) with varying degrees of renal dysfunction. Patients in group 1 (n = 5) had intrinsic renal disease and those in group 2 (n = 5) had extrinsic renal disease, as identified by the primary renal lesion. After a single intravenous dose of cefotaxime timed blood and urine samples were collected for 24 h; cefotaxime and desacetylcefotaxime were measured by HPLC. There were no significant differences between the groups in age, body surface area, urine output, creatinine clearance, total body clearance, nonrenal clearance, renal clearance, and volume of distribution at steady state of cefotaxime, and renal clearance of desacetylcefotaxime. However, the renal clearance: creatinine clearance (CLR:CLCR) ratios for both cefotaxime [1.34 in group 1 vs. 0.51 in group 2] and desacetylcefotaxime [1.58 in group 1 vs. 0.75 in group 2] were statistically significant between the two groups. Group 1 patients had an average CLR:CLCR ratio greater than 1 for both the parent compound and the metabolite, suggesting that net tubular secretion was still intact, despite a diminished glomerular filtration rate (CLCR = 24 ml.min-1.73 m-2).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8453967 TI - The effect of yohimbine on sympathetic responsiveness in essential hypertension. AB - We have studied the sympathetic response to blockade of presynaptic alpha 2 adrenoceptors in essential hypertension by measuring plasma concentrations of noradrenaline after a single oral dose of yohimbine, an alpha 2-adrenoceptor antagonist. Mean baseline plasma noradrenaline and adrenaline concentrations were similar in the hypertensive and normotensive groups. Yohimbine (0.2 mg x kg-1 orally) caused a lesser increase in the plasma concentrations of noradrenaline in hypertensive patients (+67%) than in normotensive subjects (+178%) and a pressor response in hypertensive (but not in normotensive) patients. These results are consistent with an alteration in the balance of alpha-adrenoceptors (for example presynaptic alpha 2-adrenoceptor desensitization and post-synaptic alpha 1 adrenoceptor hyper-responsiveness) which would help to develop and/or maintain arterial hypertension. PMID- 8453968 TI - Effect of chlormethiazole on hepatic monooxygenases activity in vivo. AB - Chlormethiazole is a strong inhibitor of cytochrome P-450-dependent monooxygenases in isolated human liver microsomes. To assess its effect in vivo, we measured the pharmacokinetic parameters of antipyrine (1.2 g orally) and tolbutamide (0.5 g i.v.) before and after administration of chlormethiazole 314 mg b.d. for 2 days to 8 healthy volunteers. The elimination of neither substance was affected, indicating that chlormethiazole did not inhibit in vivo the cytochrome P-450 isozymes responsible for the elimination of antipyrine and tolbutamide. PMID- 8453969 TI - Lack of interaction of ketoprofen with warfarin. AB - We gave ketoprofen (100 mg bid) for 7 days, on a placebo-controlled, double-blind basis, to 15 healthy male volunteers already stabilized on warfarin in dosages which lowered the prothrombin time by about 60%. Ketoprofen did not affect the prothrombin time, there was no change in coagulation cascade parameters, and there was no clinical evidence of bleeding. We conclude that ketoprofen in this dosage has no significance effect on the anticoagulant effect of warfarin. PMID- 8453970 TI - Lack of effect of amoxycillin on the absorption of ofloxacin. AB - Amoxycillin and ofloxacin are both well absorbed after oral administration, despite being hydrophilic. We have studied the possibility of competition between these two drugs for a carrier-mediated transport system, since both drugs are absorbed by saturable processes in the rat small intestine. Oral doses of amoxycillin (3 g) and ofloxacin (400 mg) were given separately and in combination to six healthy volunteers. Blood samples were taken over 30 h and plasma concentrations of the respective drugs were measured by HPLC. Amoxycillin did not alter the pharmacokinetics of ofloxacin. PMID- 8453971 TI - Central serotonergic uptake mechanisms in hypertensive rats: effects of clonidine and centhaquin. AB - The binding of a highly specific ligand for serotonin (5-HT) uptake sites, [3H]paroxetine, was studied in brain regions of normotensive Wistar-Kyoto rats (WKY) and spontaneous hypertensive rats (SHR). [3H]Paroxetine bound to a single, high affinity binding site in the brain. In midbrain, the density (Bmax values) of [3H]paroxetine binding were significantly reduced (27.16%) in SHR as compared to WKY. The affinity (Kd values) were found to be similar in SHR and WKY. The Kd and Bmax values of [3H]paroxetine binding were found to be similar in spinal cord, pons and medulla and cerebral cortex of WKY and SHR. The effect of centrally acting hypotensive agents, clonidine and centhaquin, on [3H]paroxetine binding was also determined and compared with imipramine, a known 5-HT uptake inhibitor. Clonidine did not displace [3H]paroxetine binding at any concentration (10(-4) to 10(-7) M). On the other hand, centhaquin, which produces hypotension similar to clonidine, could displace [3H]paroxetine binding in a concentration dependent manner. In cerebral cortex and brainstem (midbrain, pons and medulla) membranes, the IC50 values of imipramine and centhaquin for [3H]paroxetine binding were found to be similar in WKY and SHR. The IC50 of centhaquin in displacing paroxetine from 5-HT uptake sites, was 10 times lower in the cerebral cortex and 4 times lower in the brainstem membranes when compared to imipramine. Clonidine had no effect on 5-HT uptake sites. The results indicate that (1) the density of 5-HT uptake sites is reduced in the midbrain of hypertensive rats, and (2) centhaquin, a centrally acting hypotensive agent, acts on 5-HT transporter sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8453972 TI - Blockade of chronic tolerance to ethanol by the NMDA antagonist, (+)-MK-801. AB - Previous studies indicated that learning and memory play important roles in the development of tolerance to ethanol. (+)-MK-801 has been shown to impair learning and might thus also block the development of tolerance to ethanol. To test this possibility, rats were trained to criterion on the moving belt, a complex motor coordination test. Acute i.p. injection of (+)-MK-801 (a non-competitive NMDA channel blocker) produced dose-related impairment on this test. A dose of 0.1 mg/kg, that had negligible effect by itself, potentiated the acute effects of ethanol. In a chronic experiment with different animals, half of the rats received (+)-MK-801 or saline daily, followed 30 min later by ethanol (1.8 g/kg i.p.) and three practice runs on the belt, and 1 h later a second dose of (+)-MK 801 or saline. The other half received the same drugs but ethanol followed the practice. (+)-MK-801 blocked the functional tolerance to ethanol in both groups when the pre-ethanol dose was 0.25 mg/kg, but not when it was 0.1 mg/kg. Tolerance to the effects of (+)-MK-801 itself did not occur over 2 weeks of treatment. These results suggest that NMDA receptors are involved in development of chronic tolerance to ethanol as shown previously with rapid tolerance. PMID- 8453973 TI - Neurologic and histologic evaluation of almitrine+raubasine (Duxil) in middle cerebral artery occlusion in cats. AB - Impairment of energy metabolism is the fundamental mechanism leading to cell death in ischemia. Using the middle cerebral artery (MCA) occlusion model in cats, we studied the effect of Duxil (almitrine and raubasine combination), which was given either before and after or only after MCA occlusion, on ischemia in terms of neurological function and histological changes. Neurological function was assessed consecutively for 7 days after MCA occlusion using a categorical rating scale in 18 cats. Neurological function was significantly improved in treated animals than in non-treated controls regarding to the motor and sensory function, walking, posture and stepping reflex. Animals were killed on the 8th day and histological changes were examined by light and electron microscopies. Significant improvement in the morphological scores based on the light-microscopy changes were found in animals treated with Duxil compared to non-treated ones. Under the electron microscopy, the protective effects of Duxil were characterized by retaining glycogen and mitochondria. Morphological improvement was associated with the recovery of neurological function and especially profound in penumbra areas of MCA infarction. These results suggest that Duxil has a protective effect against ischemic damage induced by occlusion of MCA in cats. PMID- 8453974 TI - Involvement of ATP-sensitive K+ channels in the sustained coronary vasodilator response to adenosine in dogs. AB - Coronary vasodilator mechanisms of adenosine were investigated in isolated canine papillary muscle preparations cross-circulated through the anterior septal artery with support dogs. Infusions of adenosine (1-3000 nmol/min) for 3 min into this artery caused a transient increase (the initial phase) in blood flow followed by a sustained increase (the sustained phase), and single-bolus intra-arterial injections of adenosine (0.3-1000 nmol) produced only a transient increase in blood flow. The force of contraction of the papillary muscle was virtually unaffected. The increase in blood flow in the sustained phase was antagonized by glibenclamide (6 mumol/kg i.v.), a blocker of ATP-sensitive K+ channels, administered to support dogs whereas increases in both phases were antagonized by 8-phenyltheophylline (12 mumol/kg i.v.), a non-selective adenosine receptor antagonist, administered in a similar way. The transient increase in blood flow caused by single-bolus injections of adenosine was reduced in duration rather than in peak value by glibenclamide. Thus, it appears that opening of ATP sensitive K+ channels gradually becomes involved in the vasodilator mechanisms for adenosine A2 receptor-mediated, sustained vasodilation. PMID- 8453975 TI - Lack of tolerance to ethanol-induced dopamine release in the rat ventral striatum. AB - The effect of ethanol challenge on the extracellular concentrations of dopamine, 3,4-dihydroxy-phenylacetic acid and homovanillic acid was studied in the ventral striatum of rats repeatedly treated with ethanol. Ethanol-treated animals (1 g/kg i.p. twice a day for 12 days) developed marked tolerance to the behavioral signs of ethanol intoxication when challenged with ethanol (2 g/kg i.p.). However, in ethanol-treated animals the increased output of dopamine and metabolites after ethanol challenge (1 or 2 g/kg i.p.) was not statistically different from that observed in saline-treated rats. These results indicate that tolerance does not develop to the ethanol-induced stimulation of dopamine release and support the hypothesis that activation of the mesolimbic dopamine system contributes to the reinforcing properties of ethanol. PMID- 8453976 TI - Nitric oxide-dependent and -independent neurogenic relaxation of isolated dog urethra. AB - In the presence of adrenergic and cholinergic blocking agents, transmural electrical stimulation evoked a relaxation in isolated dog urethra precontracted with histamine. The response was abolished by tetrodotoxin, indicating its neurogenic origin. The non-adrenergic and non-cholinergic relaxation developed rapidly and was transient at low stimulation frequencies (< or = 1 Hz). However, at higher frequencies (> or = 5 Hz) the recovery phase of the relaxation became slow and often showed a notch, suggesting the presence of transient and slow components. NG-Monomethyl-L-arginine, a nitric oxide synthase inhibitor, inhibited the transient relaxation but did not affect the relaxation evoked at high stimulation frequencies. NG-Nitro-L-arginine, a more potent nitric oxide synthase inhibitor, abolished the transient relaxation produced at low stimulation frequencies and markedly attenuated the transient component at high frequencies. However, NG-nitro-L-arginine did not affect the slow component. The inhibition by NG-monomethyl-L-arginine and NG-nitro-L-arginine was reversed by the addition of L- but not D-arginine. Exogenously applied vasoactive intestinal polypeptide (VIP) produced a slowly developing relaxation. The slow relaxation induced by transmural electrical stimulation and VIP was not affected by [4-Cl-D Phe6,Leu17]VIP, a reportedly competitive VIP antagonist. NG-Nitro-L-arginine did not affect the relaxation induced by VIP and sodium nitroprusside. These results suggest that the non-adrenergic and non-cholinergic relaxation induced by transmural electrical stimulation is composed of nitric oxide-dependent and independent components in the isolated dog urethra. PMID- 8453977 TI - Endothelium-dependent control of vascular tone in the rabbit kidney after ischemia and reperfusion. AB - We investigated the effects of renal ischemia with reperfusion on the reactivity of rabbit renal vasculature. The main renal and arcuate arteries were isolated and studied as ring preparations. In the renal artery, concentration-response curves for potassium chloride (KCl), noradrenaline (NA), serotonin (5-HT), angiotensin II (AII), acetylcholine (ACh), A23187 or sodium nitroprusside (SNP) were unaltered after ischemia and reperfusion. Under the same conditions, the relaxation of arcuate arteries elicited by ACh was reduced when vessels were precontracted with methoxamine but not with KCl, whereas SNP-induced responses were unaffected. In anesthetized rabbits, renal blood flow and corresponding renal vascular resistances (RVR) were not modified by ischemia and reperfusion. ACh (1, 3 and 10 micrograms/kg per min) reduced RVR (maximally -24 +/- 8%) and this response was unchanged after ischemia and reperfusion (maximally -25 +/- 10%). These results demonstrate that the rabbit renal vasculature is relatively resistant to an ischemic insult and is probably not involved in the development of postischemic renal failure. PMID- 8453978 TI - Evidence for a role of 5-HT1C receptors in the antiserotonergic properties of some antidepressant drugs. AB - A variety of antidepressants of different chemical classes were tested for their in vivo and in vitro activity at 5-HT1C receptors in the brain. Conventional tricyclic antidepressants (imipramine, desipramine, maprotiline, clomipramine, trimipramine, amitriptyline, nortriptyline, doxepin, amoxapine) as well as mianserin and trazodone were found to display high to low nanomolar affinity for 5-HT1C receptors. Antidepressants of other chemical classes and with other mechanisms of action (affecting amine uptake systems: fluoxetine, citalopram, sertraline, fluvoxamine, nomifensine, amineptine; or monoamine oxidase inhibitors: moclobemide, iproniazid) had negligible affinities (micromolar range) for 5-HT1C receptors, except fluoxetine. When tested in an in vivo rat model thought to reveal functional agonistic or antagonistic properties at 5-HT1C receptors, all antidepressants displaying high affinity for this receptor type (except clomipramine and trimipramine) were antagonists at 5-HT1C receptors. Antidepressants with a lower affinity for 5-HT1C receptors (except nomifensine) were inactive in this functional in vivo model. Taken together, these results suggest that antagonism at brain 5-HT1C receptors is a component of the antiserotonergic properties of a number of established antidepressants. In addition, the study confirmed that 5-HT1A receptors functionally interact with 5 HT1C receptors, which suggests that some degree of activity at 5-HT1A receptors may also be an important property for antidepressant activity. PMID- 8453979 TI - Platelet-activating factor and the vascular effects of zymosan in rats. AB - Platelet-activating factor (PAF; 2.5 micrograms/kg) injected in the tail vein of anaesthetized rats increased the vascular permeability of the duodenum, paws, skin and muscles, as measured by the extravasation of 125I-labelled albumin. It did not affect the permeability of the lungs or the presence of labelled albumin in the liver and spleen. The effects of PAF were dose dependently inhibited by WEB 2086 (ID50: 1.39 to 2.09 mg/kg) and SM-12502 (ID50: 7.17 to 8.36 mg/kg). Zymosan, an activator of the alternative complement pathway (10 or 16 mg/kg), induced protein extravasation in the lungs, duodenum, paws and skin, and the accumulation of labelled albumin in the liver. The effects of zymosan on the duodenum and liver were dose dependently inhibited by WEB-2086 and SM-12502. Both PAF antagonists increased the effects of zymosan in the paws but they did not affect protein extravasation in the lungs. The hypotensive effect of PAF (0.5 micrograms/kg) was inhibited by WEB 2086 (ID50: 1.21 mg/kg) and SM-12502 (ID50: 13.4 mg/kg). Both PAF antagonists reduced the hypotensive effects of zymosan (4 or 16 mg/kg) with a similar relative inhibitory potency. PAF is the major mediator involved in the hypotensive effect of zymosan but plays only a minor role in the permeability-enhancing effect of zymosan, mostly in the splanchnic area. PMID- 8453980 TI - Increases in rat striatal extracellular dopamine and vacuous chewing produced by two sigma receptor ligands. AB - The present studies were carried out to analyze the neurochemical and behavioral effects of peripheral sigma ligand administration in the rat. Based upon previous studies which showed an increase in turning behavior following unilateral intranigral administration of sigma ligands, we determined the effects of two sigma ligands, 1,3-di-o-tolylguanidine (DTG) and (+)-pentazocine, on extracellular dopamine levels in the rat striatum. Dopamine levels were monitored via microdialysis in awake freely moving animals following i.p. injection of the ligands. Both DTG (1 and 3 mg/kg) and (+)-pentazocine (10 mg/kg) produced a significant (30-50%) increase in extracellular dopamine. Given the relatively high concentration of sigma receptors in brain nuclei involved in facial and mouth movements, we have also determined the effects of the two sigma ligands on facial movements. Both ligands produced a significant increase in vacuous chewing movements, suggesting that studies on the consequences of sigma receptor activation may have relevance to animal models of human dystonia and/or dyskinesia. PMID- 8453981 TI - Vascular interaction between 5-hydroxytryptamine and 15-lipoxygenase metabolites of arachidonic acid. AB - In isolated canine saphenous veins, the contractions elicited by the 15 lipoxygenase metabolites 15-HETE and 15-HPETE were augmented by 5 hydroxytryptamine (5-HT) in a concentration-dependent way. This potentiation was not mediated by the endothelium nor was it influenced by the 5-HT2-antagonist ketanserin. Phentolamine, however, reduced both the contractions and the potentiation by 5-HT. These data provide evidence for a receptor-mediated potentiation by 5-HT which occurs independently of 5-HT2-receptors. The interaction between 5-HT or aggregating platelets and 15-HPETE was studied in isolated rabbit brachiocephalic arteries. Threshold concentrations of 5-HT and platelets markedly potentiated the contractions elicited by 15-HPETE. In brachiocephalic arteries obtained from cholesterol-fed rabbits, 15-HPETE, 5-HT and platelets caused contractions similar to those obtained in control rabbits. The potentiating effect of 5-HT and platelets on the 15-HPETE-induced contractions was also comparable to that observed in control rabbits. Moreover, no difference was found between control platelets and platelets obtained from hypercholesterolemic rabbits. Our findings demonstrate a positive interaction between 5-HT and 15-lipoxygenase metabolites of arachidonic acid in arteries and veins. This interaction persists in atherosclerotic arteries and could indicate that this mechanism is involved in the genesis of vasospasm. PMID- 8453982 TI - Aniracetam reverses the anticonvulsant action of NBQX and GYKI 52466 in DBA/2 mice. AB - Aniracetam (1-p-anisoyl-2-pyrrolidinone) selectively reverses the anticonvulsant activities of the non-NMDA receptor antagonists, GYKI 52466 (1-(4-aminophenyl)-4 methyl-7,8-methylenedioxy-5H-2,3- benzodiazepine.HCl) and, to a lesser extent, NBQX (2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline), without affecting the anticonvulsant activity of the competitive NMDA receptor antagonist, D(-) CPPene, in DBA/2 mice. Pretreatment with aniracetam (50 nmol i.c.v., 15 min before drugs) increases the ED50 values (mumol/kg i.p., 15 min) for GYKI 52466 induced protection against sound-induced clonic seizures in DBA/2 mice 7 fold, from 20.1 (11.9-33.9) to 142 (91.7-219), and for NBQX-induced protection 2 fold, from 39.7 (33.8-46.7) to 85.6 (63.9-115), respectively. Aniracetam on its own (12.5-100 nmol i.c.v.) has no convulsant activity, but reverses the anticonvulsant effect of GYKI 52466 (60 mumol/kg i.p., 15 min) in a dose dependent manner. PMID- 8453983 TI - Nuclear assembly, structure, and function: the use of Xenopus in vitro systems. PMID- 8453984 TI - An endoplasmic reticulum protein, calreticulin, is transported into the acrosome of rat sperm. AB - Recently, we purified a Ca(2+)-binding protein from rat spermatogenic cells [Biochem. Biophys. Res. Commun. 176, 135-1364, 1991]. In the present study, this protein was identified as calreticulin, which is a resident protein of the endoplasmic reticulum (ER). Immunohistochemical studies revealed that calreticulin was present in the acrosome of both round spermatids and mature sperm. However, under immunoelectron microscopy, gold-particles were seen over other subcellular structures of spermatocytes, spermatids, and Sertoli cells. When the labeling density in subcellular structures of spermatids was analyzed, the acrosome was found to be most heavily labeled and the Golgi apparatus was second. The complete amino acid sequence of calreticulin, deduced from the cDNA sequence, shares a high degree of identity with that of the analogous mouse protein. The cDNA encoded a protein of 416 amino acids, including a 17-residue NH2-terminal signal sequence. The mature protein contains a KDEL sequence as an ER signal at the COOH terminus. Sperm calreticulin contained no glycosyl moiety. Northern blot analysis of RNAs from purified populations of rat spermatogenic cells indicated that the calreticulin mRNA was present in both pre- and postmeiotic cells. Immunoblot analysis of calreticulin during developmental stages showed that calreticulin was detected in the testis between the ages of 5 and 50 days. Furthermore, purified rat calreticulin contained two Ca(2+)-binding sites, a low affinity/high capacity site and a high affinity/low capacity site. These results suggest that calreticulin, which is not specific to testis, is closely associated with spermatogenesis of rats. This ER protein may be incorporated into the acrosomal vesicle via the Golgi apparatus, without glycosylation, during spermiogenesis, and may play an important role in the regulation of cell functions such as sperm motility and acrosome reaction. PMID- 8453985 TI - Insights into the function of a sperm-surface progesterone receptor: evidence of ligand-induced receptor aggregation and the implication of proteolysis. AB - Human spermatozoa have recently been introduced as a model for the study of rapid, nongenomic effects of steroids on the cell. Indirect evidence suggests the presence of a novel type of progesterone receptor on the cell surface; some cellular responses mediated by the receptor have been shown to be sensitive to protease inhibitors, but the molecular identity and the mode of function of this receptor are not known. Recent biochemical evidence showed that Ca2+ influx and a Ca(2+)-dependent exocytotic event (the acrosome reaction) can be induced in human sperm by antibody-mediated aggregation of the cell-surface progesterone receptor. These data suggested that progesterone receptor aggregation, occurring after ligand binding, may represent an early reaction in the signal transduction pathway. In this study we used cytological methods to examine ligand-induced changes in the distribution of the progesterone receptor in the sperm plasma membrane. We also examined the effects of trypsin and of trypsin inhibitors on the function of the receptor. Under the conditions of this study, neither trypsin nor trypsin inhibitors affected sperm viability, motility, or the acrosome reaction. However, the trypsin treatment completely abolished the ligand-binding activity of the sperm progesterone receptor. On the other hand, trypsin inhibitors did not influence the ligand binding despite their inhibitory effect on the ligand-induced exocytosis. The treatment with trypsin inhibitors was thus used to prevent the exocytotic reaction and so to preserve the plasma membrane for the study of ligand-induced receptor migration. The distribution of ligand receptor complexes in the sperm acrosomal region remained homogeneous during incubation at 4 degrees C, but warming to 37 degrees C entailed a rapid formation of patches, followed by migration of the complexes towards the sperm equatorial region and ending by a virtually complete disappearance of the complexes from the anterior acrosomal region. It is concluded that aggregation is an early response of the sperm-surface progesterone receptor to ligand binding, that trypsin inhibitors block the function of the receptor downstream of the aggregation, and that some mechanism must exist in the plasma membrane to protect the ligand binding site from digestion while permitting the protease action in the signal transduction mechanism. PMID- 8453986 TI - Characterization of two distinct pathways of endocytosis of ricin by rat liver endothelial cells. AB - We have studied the characteristics of internalization and intracellular transport of ricin via two distinct pathways in rat liver endothelial cells (EC), i.e., via binding to mannose receptors and surface galactosyl-residues, respectively. Treatments that inhibit endocytosis from coated pits, i.e., hyperosmolarity and acidification of the cytoplasm, decreased uptake via mannose receptors much more than uptake via galactosyl-residues, indicating that mannose receptors are largely internalized from coated pits, whereas internalization via galactosyl-residues is to a significant extent independent of coated pits. Uptake of ricin via mannose receptors was strongly inhibited by NH4Cl and monensin, and accordingly, NH4Cl protected the cells against ricin intoxication via mannose receptors. On the other hand, uptake via galactosyl-residues was not significantly inhibited by NH4Cl or monensin, and NH4Cl even sensitized the cells to intoxication via this pathway. Brefeldin A, which did not affect ricin uptake, protected the cells against ricin intoxication via either pathway. Protein synthesis in the EC was efficiently inhibited by ricin, even after very short periods of uptake at low ricin concentrations. The onset of protein synthesis inhibition was more rapid upon internalization of ricin via mannose receptors than via galactosyl-residues. Also, ricin internalized via mannose receptors was more efficiently transported from endosomes to lysosomes than ricin internalized via galactosyl-residues. Partial blocking of the galactosyl-binding sites of ricin caused a reduction in the extent of recycling of ricin from endosomes to the cell surface (retroendocytosis), indicating that binding of ricin to membrane galactosyl-residues, which is relatively stable at the slightly acidic pH of endosomes, is an important determinant of the intracellular handling of ricin. We suggest that the observed difference in the transport from endosomes to lysosomes between the two internalization pathways is related to the different stability of the two binding mechanisms at endosomal pH. PMID- 8453987 TI - Two steps required for male pronucleus formation in the sea urchin egg. AB - We have developed a system for microinjection of sea urchin sperm nuclei into live eggs and oocytes in order to study conditions which are required for pronuclear development. The system bypasses sperm-initiated surface events that result in egg activation. By comparison to male nuclei of normally fertilized eggs or immature oocytes, the injected nuclei faithfully reflect the ability of the egg cytoplasm to promote male pronuclear development. Isolated nuclei injected into fertilized eggs swell and transform into male pronuclei like the endogenous male pronuclei. Nuclei injected into immature oocytes remain conical like fertilizing sperm nuclei. If sperm nuclei are injected into unfertilized, unactivated eggs, they undergo incomplete decondensation and fail to form pronuclei. This partial decondensation can be inhibited with 6 dimethylaminopurine (6-DMAP). If unfertilized eggs are first incompletely activated by raising internal pH with ammonia, injected sperm nuclei will complete pronuclear development. Increasing pH or Ca2+ does not cause sperm nuclear swelling or chromatin decondensation in immature oocytes. These experiments reveal two conditions necessary for pronuclear formation. The first condition, resulting in partial decondensation, develops during meiotic maturation and can be blocked by 6-DMAP. The second requires cytoplasmic alkalinization, but not the fertilization-induced internal Ca2+ increase or inositol triphosphate pathway activation. PMID- 8453988 TI - Cell cycle-dependent distribution of telomeres, centromeres, and chromosome specific subsatellite domains in the interphase nucleus of mouse lymphocytes. AB - Fluorescence in situ hybridization and 3-D image analysis were combined to study the distribution of specific chromosome subdomains through the course of the cell cycle in cultured mouse lymphocytes. DNA probes specific for major satellite DNA, minor satellite DNA, telomeric DNA and to chromosome X-, 8-, and 14-specific subsatellite DNA sequences were used. We demonstrate that a redistribution of the chromatin occurs during the cell cycle in the interphase nucleus, and that the profile of the rearrangement is highly dependent on the nature of the domain considered (centromeres, telomeres, or subsatellite regions). However, the relative arrangement of chromosome homologs to each other does not appear to be spatially defined or regulated. PMID- 8453989 TI - Light and electron microscope immunocytochemical analyses of histone H1(0) distribution in the nucleus of Friend erythroleukemia cells. AB - The localization of histone H1(0) in murine erythroleukemia cells which were induced to resume a differentiation program was studied in cells which have recovered their proliferative capacity after transient blockage in the G1 phase of the cell cycle. Previous studies have shown that histone H1(0) accumulation occurs at early times of induction and is probably related to the commitment itself. The distribution of the protein was determined by immunomicroscopy with monoclonal antibodies specific for histone H1(0). Our observations showed that the histone accumulates in nuclei. Immunoelectron microscopy further demonstrated the presence of histone H1(0) in condensed chromatin areas, including perinucleolar chromatin. Moreover, histone H1(0) also occurred in the perichromatin regions, previously described as preferential sites of pre-mRNA synthesis, suggesting that histone H1(0) is not fully excluded from active chromatin. PMID- 8453990 TI - Characterization of the plasminogen activators and plasminogen activator inhibitors expressed by cells isolated from rabbit ligament and synovial tissues: evidence for unique cell populations. AB - Fibroblasts derived from rabbit anterior cruciate and medial collateral ligaments were found to constitutively produce and secrete a plasminogen activator (PA). The PA was identified as urokinase-like using biochemical, immunological, and molecular techniques. These fibroblasts also produced and secreted low levels of a plasminogen activator inhibitor (PAI). The inhibitor was identified as PAI-1 by biochemical and molecular techniques. The expression of both PA and PAI activity in the rabbit ligament fibroblasts increased upon addition of phorbol myristate acetate (PMA). To determine the relationship of the ligament fibroblast population to synovial fibroblasts, comparison of the biochemical characteristics of the cell types was performed. It was determined that synovial fibroblasts differed from ligament fibroblasts with respect to PA/PAI profile, type of collagen secreted, and the amount of hyaluronic acid secreted. More specifically, stimulation of synovial fibroblasts with PMA resulted in the detection of a fibrinolytic activity which was not detected in the conditioned medium from PMA treated ligament fibroblasts. It was also shown that synovial fibroblasts secreted fourfold more hyaluronic acid than ligament fibroblasts. In addition, it was also determined that synovial fibroblasts secrete more type III collagen than do cells isolated from either the ACL or either MCL. These results support the conclusion that the cells derived from these tissues maintain distinct phenotypes in vitro. PMID- 8453991 TI - Regulation of nuclear transport in proliferating and quiescent cells. AB - Previously, we compared signal-mediated nuclear transport in proliferating and quiescent BALB/c 3T3 cells and found that both the relative rate of nuclear uptake and the functional size of the transport channels were significantly greater in proliferating cells. In this study, the possible causes of these permeability differences were investigated. To determine if the decrease in transport capacity in quiescent cells was due to a reduction in the availability of soluble cytoplasmic factors (i.e., ATP or receptors for nuclear location sequences), or changes in the properties of the pores themselves, proliferating and quiescent cells were fused, and nuclear import of nucleoplasmin-coated gold (NP-gold) particles was assayed in the heterokaryons 50-60 min later. Significant differences in nuclear uptake were maintained following fusion, even though the two nuclei shared a common cytoplasm, consistent with the view that permeability is regulated at the level of the pores. Cell shape also influenced signal mediated nuclear import. This was demonstrated by studying transport in rounded and flattened cells attached to different-size palladium domains that were deposited on a nonadhesive substrate. Based on analysis of the nuclear uptake rates of large (110-270 A in diameter) and small (50-80 A in diameter) coated gold particles, it was determined that the functional size of the pores was significantly greater in flattened cells. The effect of growth factors on recovery of nuclear transport capacity following serum depletion was also analyzed. Partial recovery was achieved by treating cells with physiological concentrations of EGF, IGF-1, or PDGF; however, complete recovery required both EGF and IGF-1. PMID- 8453992 TI - In vitro activation of human platelets triggered and probed by atomic force microscopy. AB - We report on the activation of human platelets probed by atomic force microscopy under nearly physiological conditions. We could image native platelets in different stages of activation at a resolution of about 100 nm. Intracellular structures within the platelets could be resolved without staining. Furthermore we could trigger and follow the activation process of individual platelets, demonstrating that the platelets are still intact and are not destroyed or severely harmed by this novel imaging process. PMID- 8453993 TI - Ligands of the antiestrogen binding site block endothelial cell proliferation reversibly. AB - Benzylphenoxyethanamine derivatives are known to display antiproliferative activities on tumor cell lines consistently with their binding affinity to the microsomal antiestrogen binding site. In the present study we show that pyrrolidinobenzylphenoxyethanamine, a new efficient compound of this series, exhibits reversible effects on exponentially growing adult bovine aortic endothelial cells inducing (1) lamellated cytoplasmic inclusions, (2) cell proliferation inhibition, (3) dose-dependent transition delay of cells in the G0 G1 phase of the cell cycle. Complete reversal of these effects is achieved only by withdrawing the drug from the medium. The ultrastructural cellular modifications disappeared, and flow cytometry and thymidine incorporation analysis showed the effect on degree of synchronization of this one-step methodology. PMID- 8453994 TI - Activation of gene expression via CArG boxes during myogenic differentiation. AB - We have studied gene activation via CArG boxes in the context of myogenesis. The proximal CArG box of the human cardiac actin gene (HCA1) stimulates transcription from the herpes simplex virus thymidine kinase (TK) promoter in a tissue-specific fashion. Thus in transient transfection assays, when the expression of chloramphenicol acetyltransferase (CAT) from p(HCA1)4 TKCAT is compared to that derived from p(M1)4 TKCAT which contains an inactive mutated version (M1) of the HCA1 element, high levels of expression are seen in C2 mouse myoblasts and myotubes, and in the T4 myoblast cell line derived from the C3H10T1/2 cell line by 5-azacytidine treatment, whereas only low levels of expression are seen in the mouse L fibroblast cell line. The parental C3H10T1/2 cell line shows intermediate levels of expression. A similar situation is seen in stably transfected cell lines. Gene activation via CArG boxes was also analyzed in the course of myogenic conversion of C3H10T1/2 cells treated with 5-azacytidine. Our results indicate that activation of the CAT gene from the HCA1 element is slightly posterior to the appearance of the first MyoD1 and myogenin transcripts, concomitant with the appearance of cardiac alpha-actin transcripts, but clearly precedes the accumulation of myosin light-chain 1a transcripts and the appearance of troponin T-positive cells. These results further establish that CArG boxes can be seen as muscle-specific cis-acting regulatory element prior to terminal differentiation. PMID- 8453995 TI - Changes in Hox1.6, c-jun, and Oct-3 gene expressions are associated with teratocarcinoma F9 cell differentiation in three different ways of induction. AB - To obtain information on the mechanism of teratocarcinoma cell differentiation, the expression of genes having a specific role in gene regulation was examined using three different methods of inducing differentiation: drug treatments with retinoic acid (RA) and sodium butyrate, and a genetic approach using ts mutants. The RAR-beta and MK genes were induced specifically by RA treatment, which indicates that these two genes are solely RA responsive. By contrast, a change in c-jun, Hox1.6, and Oct-3 gene expression was observed in all three methods of F9 cell differentiation. These findings suggest that these three genes, whether down or up-regulated, play an important and key role during teratocarcinoma cell differentiation. PMID- 8453996 TI - Cell cycle regulation of the chicken hsp90 alpha expression. AB - The heat-shock protein of 90 kDa (hsp90), constitutively expressed in most cells, is up-regulated by thermal stress and by developmental and mitogenic stimuli. When the serum-starved chicken hepatoma cell line DU249 is stimulated by serum, insulin, or growth factors acting via tyrosine kinase receptors, a transient induced expression of the hsp90 alpha gene takes place at both the messenger RNA and the protein synthesis level. This response is protein synthesis dependent and DNA synthesis independent. The maximum level of hsp90 alpha mRNA accumulation always precedes the maximum level of thymidine incorporation, suggesting a possible link between cell cycle and hsp90 alpha regulation (Jerome, V., J. Leger, J. Devin, E.E. Baulieu, and M. G. Catelli. Growth Factors 4:317-327, 1991). Herein, we examine the subcellular distribution of hsp90 and the cell cycle-dependent regulation of the hsp90 alpha mRNA level. We show that, in contrast to hsp70, the 35S metabolically-labeled hsp90, which accumulates in the cytosoluble fraction 6 to 8 h after serum treatment, is not preferentially translocated to the nuclear compartment, although a small fraction is always present in the nucleus. We also demonstrated that serum- or insulin-induced accumulation of hsp90 alpha mRNA results from an activation of gene transcription and that hsp90 alpha promotor activity, which is low in quiescent DU249 cells, is induced approximately fivefold after serum stimulation. Finally, in cell culture synchronized by nocodazole or aphidicholin, hsp90 alpha mRNA accumulation seems an event specific to G1/S transition. PMID- 8453997 TI - An oligomer targeted against protein kinase C alpha prevents interleukin-1 alpha induction of cyclooxygenase expression in human endothelial cells. AB - We have previously demonstrated that interleukin-1 alpha (IL-1), a potent polypeptide mediator of immune and inflammatory responses, induces the expression of cyclooxygenase (cox) in human endothelial cells. The mechanism by which binding of IL-1 to its receptor stimulates gene expression remains unclear. Since phorbol 12-myristate 13-acetate, which directly binds and activates protein kinase C (PKC), induced cox expression, we examined the role of PKC as an intracellular mediator of IL-1 activity in human endothelial cells. IL-1 induced the translocation of PKC from the cytosol to the membrane. H7, a selective inhibitor of PKC, as well as an antisense oligomer blocking PKC alpha translation suppressed IL-1 induction of cox mRNA. These findings establish that PKC plays a role in the signal transduction pathway leading to the induction of cox in human endothelial cells. PMID- 8453998 TI - Import of firefly luciferase into peroxisomes of permeabilized Chinese hamster ovary cells: a model system to study peroxisomal protein import in vitro. AB - A model system for the study of in vitro peroxisomal protein import is described. Chinese hamster ovary (CHO) cells were permeabilized by the bacterial toxin streptolysin O (SLO) and their peroxisomes thus became accessible for a model import protein. Firefly luciferase (FL), which was previously shown to be imported into mammalian peroxisomes in vivo, was used as the reporter protein. When SLO-permeabilized CHO cells were incubated with FL in the presence of an ATP regenerating system, import of FL could be documented by immunofluorescence staining of the cells with monospecific anti-FL antiserum. FL import increased with time and was dependent on temperature and the presence of hydrolysable ATP, which could not be replaced by GTP. The model system functioned reproducibly and should be of use for investigating fundamental questions on the mechanism of peroxisomal protein import. PMID- 8453999 TI - Import of firefly luciferase into mammalian peroxisomes in vivo requires nucleoside triphosphates. AB - The insect enzyme firefly luciferase (FL), which is known to be imported into mammalian peroxisomes as well, was introduced into the cytoplasm of chinese hamster ovary cells and human skin fibroblasts by microinjection. This model system was used to study the nucleoside triphosphate dependence of peroxisomal protein import by immunofluorescence staining of FL following depletion of cellular ATP. In energized cells a punctate staining pattern of the enzyme is observed between 30 min and 1 week after microinjection suggesting an organellar localization of FL. Evidence for its peroxisomal localization was gained by comparison of the FL staining pattern with that of catalase, a peroxisomal marker. Differential permeabilization of cells with digitonin prior to immunofluorescence staining demonstrated the intraperoxisomal localization of microinjected FL and excluded the possibility that FL is merely adhering at the cytosolic face of peroxisomes without being imported. Depletion of cellular ATP by the metabolic inhibitors 2-deoxyglucose and NaN3 completely prevented import of FL into peroxisomes whereas upon reenergizing the cells FL import was restored. The import steps that may be responsible for the observed energy dependence are discussed. PMID- 8454000 TI - Modulation of the phosphorylation of glucose-regulated protein, GRP78, by transformation and inhibition of glycosylation. AB - The phosphorylation of glucose-regulated protein, GRP78, is thought to be involved in the regulation of the binding function of GRP78 to immunoglobulin heavy chains. The phosphorylation of GRP78 proceeded faster in transformed cells than in normal cells, whereas the levels of GRP78 synthesis and accumulation were similar in both cells. Treatment of the cells with tunicamycin caused a rapid decrease in GRP78 phosphorylation within 2 to 4 h in both cell types prior to GRP78 induction. Following a longer period of tunicamycin treatment, GRP78 phosphorylation recovered gradually in parallel with the accumulation of newly synthesized GRP78. The half-life of GRP78 was over 24 h and similar in both normal and transformed cells either with or without tunicamycin treatment. In contrast, the half-life of phosphate groups incorporated into GRP78 was about 120 min in both types of cells in the absence of tunicamycin treatment. When the cells were treated with tunicamycin, the half-life of the phosphate groups was shortened (-30 min) only in transformed cells, while it remained at untreated control levels in normal cells. These results suggest that GRP78 phosphorylation is important in functional regulation, and that the cells may carry out particular requirements such as increasing or decreasing secretory proteins by modulating GRP78 phosphorylation rather than GRP78 synthesis. PMID- 8454001 TI - Rostrocaudal gradients in the neuronal receptive field complexity in the finger region of the alert monkey's postcentral gyrus. AB - In the primate postcentral gyrus, the cytoarchitectonic characteristics gradually shift from those of koniocortex to more homotypical parakoniocortex along its rostrocaudal axis. To find the physiological correlates of these changes we examined a large body of data accumulated during a series of our experiments with alert monkeys. Along the rostrocaudal axis of the postcentral gyrus, we found a gradual and continuous increase in the number of neurons with converging receptive fields and those in which receptive field positions or submodalities were not determined. Deep or skin submodality neurons were dominant in area 3a or 3b respectively. The proportion of skin submodality neurons decreased gradually from area 3b to the more caudal part of the gyrus. The proportion of deep submodality neurons was almost constant from area 3b to area 2 inclusive; they were not the majority in area 2. The data are consistent with the hierarchical scheme, i.e., within the postcentral gyrus sensory information is processed from the primary sensory receiving stage to the more associative, integrative stages. PMID- 8454002 TI - Early development of the SI cortical barrel field representation in neonatal rats follows a lateral-to-medial gradient: an electrophysiological study. AB - Development of the barrel field in layer IV of SI cortex of neonatal rats was studied in vivo using electrophysiological recording techniques. This study was designed to determine (a) the earliest time SI cortex is responsive to peripheral mechanical and/or electrical stimulation and (b) whether the development of the SI cortical barrel field map of the body surface follows a differential pattern of development similar to the pattern previously demonstrated using peanut agglutinin (PNA) binding (McCandlish et al. 1989). Carbon fiber microelectrodes were used to record evoked responses from within the depth of the cortex in neonatal rats between postnatal day 1. (PND-1), defined as the day of birth, and PND-14. Evoked responses were first recorded approximately 12 h after birth. These responses in the youngest animals were of low amplitude, monophasic waveshape, and long latency, with long interstimulus intervals necessary to drive the cortex. Increases in amplitude and complexity of waveshape and decreases in latency were observed over subsequent postnatal days. The earliest responses recorded on middle PND-1 were evoked by stimulation of the face and/or mystacial vibrissae. The next responses were evoked approximately 24 h after birth (late PND-1) by stimulation of the forelimb. The last responses were evoked approximately 36 h after birth (middle PND-2), by stimulation of the hindlimb. The physiological map of the representation of the body surface follows a developmental gradient similar to the gradient observed using PNA histochemistry; however, the lectin-generated morphological map lagged approximately 48 h behind the physiological map.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454003 TI - Unilateral cholinergic stimulation of the rabbit's cerebellar flocculus: asymmetric effects on optokinetic responses. AB - In previous work, we have demonstrated an acceleration of the buildup of slow phase velocity of optokinetic nystagmus (OKN) after bilateral floccular injection of the aselective cholinergic agonist carbachol (Tan and Collewijn 1991; Tan et al. 1992a). In the present study we investigated the effects of unilateral floccular injections of carbachol. Such unilateral injections specifically enhanced the buildup of OKN slow-phase velocity in the direction toward the injected flocculus (ipsiversive). During binocular optokinetic stimulation, this enhancement was expressed in the motion of both eyes. Acceleration of the eye contralateral to the injected flocculus increased from 1 to about 2 degrees/s2, while the acceleration of the ipsilateral eye increased from 1 to about 1.5 degrees/s2. In contrast, buildup of contraversive OKN was unchanged. No changes were found in the steady-state OKN and optokinetic afternystagmus (OKAN). Monocular optokinetic stimulation was only effective in the nasal direction, and the effects of unilateral injection of carbachol were disconjugate. Ipsiversive OKN was enhanced only in the contralateral, seeing eye, while the response of the ipsilateral, covered eye was unchanged. We hypothesize that the directionally specific effect of unilateral cholinergic floccular stimulation on OKN is due to enhancement of predominantly the excitatory phase of modulation of the Purkinje cell's simple-spike activity by carbachol, without a marked effect of carbachol on the inhibitory phase of simple-spike modulation. PMID- 8454004 TI - Shortening of vestibular nystagmus in response to velocity steps by microinjection of carbachol in the rabbit's cerebellar flocculus. AB - It has been proposed that a common velocity-storage mechanism is responsible for the prolongation of vestibular nystagmus beyond the duration of the change in firing frequency of primary vestibular fibers in response to a step in velocity, and for the production of optokinetic afternystagmus (OKAN). In a previous study, bilateral injection of the aselective cholinergic agonist carbachol in the flocculus shortened the duration of buildup of optokinetic nystagmus (OKN) and the duration of OKAN, suggesting floccular involvement in velocity storage (Tan et al. 1992). In extension to that study of OKN, the present study assesses the effects of floccular carbachol on vestibular nystagmus in response to velocity steps. Our results show that injection of carbachol shortens the duration of vestibular nystagmus from about 13 to about 8 s; a finding which supports a common velocity-storage mechanism for optokinetic and vestibular signals. We propose that the indistinguishable effects of carbachol on OKAN and vestibular nystagmus are due to modification of the transmission of an oculomotor corollary signal, which has been identified electrophysiologically in the flocculus. PMID- 8454005 TI - An electrophysiological study of a transient ipsilateral interpositorubral projection in neonatal cats. AB - We examined whether transient projections in the developing central nervous system of Mammalia form functional synapses on their target neurons, using transient ipsilateral interpositorubral (iIR) projection in kittens as a model system. Intracellular recordings were made from red nucleus (RN) neurons in 26 kittens aged 6-26 postnatal days (PD6-26). RN neurons were identified by monosynaptic excitatory postsynaptic potentials (EPSPs) evoked by stimulation of contralateral nucleus interpositus (IN), and additionally by intracellular staining in a few cells. Sixty-nine out of 362 RN neurons responded to stimulation of the ipsilateral IN. Of the 69 cells, 25 showed depolarizing responses with relatively short latency (2.1-6.7 ms) in kittens up to PD20. Such responses were not observed in older animals. Varying stimulus strength revealed that the potentials were unitary. Paired-pulse facilitation of the potential was observed, suggesting that the depolarizations are EPSPs. Several lines of evidence were obtained suggesting that the EPSPs are evoked monosynaptically. They followed high-frequency stimulation up to 50 Hz, and their latencies remained constant with varying stimulus strength. The latencies of ipsilaterally induced EPSPs were always longer than those of contralateral ones, evidence consistent with the longer course of ipsilaterally projecting axons than that of contralateral ones (Song and Murakami 1990). The age of disappearance of the monosynaptic EPSPs, i.e., PD20, also corresponds roughly with that of the anatomically demonstrable iIR fibers (PD15-PD25; Song and Murakami 1990). It is thus concluded that the transient iIR fibers in kittens form functional synapses on RN neurons. PMID- 8454006 TI - Disynaptic excitation from the medial longitudinal fasciculus to lumbosacral motoneurons: modulation by repetitive activation, descending pathways, and locomotion. AB - Short-latency excitatory postsynaptic potentials (EPSPs) evoked by stimulation in the medial longitudinal fasciculus (MLF) were recorded intracellularly from motoneurons in the cat lumbosacral spinal cord. Monosynaptic and disynaptic EPSPs occurred in most flexor and extensor motoneurons studied. These EPSPs resulted from the activation of fast (> 100 m/s) descending axons from the MLF to the spinal cord. Several features distinguished monosynaptic and disynaptic MLF EPSPs. Disynaptic EPSPs exhibited temporal facilitation during short trains of stimulation, whereas monosynaptic EPSPs did not. Disynaptic EPSPs, but not monosynaptic EPSPs, were also facilitated by stimulation of the pyramidal tract and the mesencephalic locomotor region. However, disynaptic MLF EPSPs exhibited little or no facilitation when conditioned by short-latency cutaneous pathways. During fictive locomotion, the amplitude of disynaptic MLF EPSPs was modulated, with maximal amplitudes during the step cycle phase when the recorded motoneuron was active, resulting in reciprocal patterns of modulation of flexors and extensors. No comparable change was seen in the amplitude of monosynaptic MLF EPSPs during fictive stepping. These data suggest that the central pattern generator for locomotion modulates disynaptic MLF excitation at a premotoneuronal level in a phase-dependent manner. The effects of lesions made in the MLF and thoracic cord suggest that the interneurons in the disynaptic pathway from the MLF to motoneurons reside in the lumbosacral cord. PMID- 8454007 TI - The influence of mechanical stimuli and of acetylsalicylic acid on the discharges of slowly conducting afferent units from normal and inflamed muscle in the rat. AB - In anaesthetized rats, the influence of an experimental inflammation and of acetylsalicylic acid (ASA) on the discharge properties of muscle receptors with slowly conducting afferent fibres was studied using a single-fibre recording technique. Following the induction of a myositis with carrageenan, the proportion of units having background activity and the frequency of the background discharge were significantly increased. The latter change was particularly prominent in high-threshold mechanosensitive (HTM) units. There was evidence for an inflammation-induced lowering of mechanical threshold in HTM units, but the change was not statistically significant. Administration of ASA intravenously led to a decrease in the frequency of background discharge in some units while others were unaffected, although they appeared to be sensitized by the inflammation. If one assumes that at least some of the HTM receptors fulfil nociceptive functions, the results suggest that the pain and tenderness of an inflamed muscle is largely due to a sensitization and hence increased activity of nociceptive muscle receptors. The sensitization is only partially abolished by ASA. PMID- 8454008 TI - Dynamic changes in the receptive field properties of spinal cord neurons with ankle input in rats with chronic unilateral inflammation in the ankle region. AB - The aim of this study was to determine the discharge and receptive field properties of spinal cord neurons with ankle input in spinal segments L4-6 in the rat, both under control conditions and during the course of an adjuvant-induced unilateral inflammation in the ankle. The extent of receptive fields in the skin and deep tissue was assessed using brush, pinch and compression stimuli. Neurons were categorized as nociceptive-specific or wide-dynamic-range neurons on the basis of their response thresholds and responses to suprathreshold stimuli. At all stages of inflammation (2, 6, 13 and 20 days post inoculation) the population of neurons with ankle input showed differences from the population of neurons with ankle input in control rats. There was a reduction in the number of neurons that appeared as nociceptive specific and a concomitant increase in the number of neurons showing a wide-dynamic-range response profile. The receptive fields of the neurons with ankle input were markedly larger in rats with inflammation in the ankle region and mainly spread proximally on the ipsilateral hindlimb and also to the abdomen and tail in some cases. There was also an increase in the number of neurons with contralateral excitatory inputs. The mechanical thresholds at the ankle joint and proximal parts of the ipsilateral hindlimb were less in arthritic rats than in controls. The proportion of spontaneously active neurons was also increased in rats during the initial and later stages of inflammation, although there was no significant increase in the mean spontaneous discharge frequency. These data show that there are long-term changes in the receptive field and response properties of neurons in intact rats with chronic unilateral adjuvant-induced inflammation similar to those described previously in spinal cats with acute inflammation (Neugebauer and Schaible 1990). It is presumed that similar afferent and spinal mechanisms are at work under acute and chronic inflammatory conditions which produce hyperexcitability in spinal neurons with joint input. PMID- 8454009 TI - Alterations in visual receptive fields in the superior colliculus induced by amphetamine. AB - Visual response properties were examined in the superficial layers of the superior colliculus (SC) of anesthetized, paralyzed cats before and after i.v. administration of d-amphetamine. Receptive fields (RFs) of single SC units were plotted using small spots of light presented to the contralateral eye. Within the first hour following d-amphetamine injections, RF size gradually increased, reaching a maximum 86 min post-injection. On average, the area of the RF increased by 5.6 times and RF expansion was observed in all single units examined in the superficial layers. Over the subsequent 4-8 h following the injection, RF area gradually decreased and returned to control dimensions. Most RFs displayed asymmetrical patterns of expansion, showing relatively more horizontal than vertical growth. As RF expansion developed, responses to stimuli flashed "on" and "off" at various locations both inside and outside the borders of the control RF became progressively more vigorous. In contrast, no significant changes were noted in direction-selective responses at any time after d-amphetamine injections. Using an array of light bar stimuli of different lengths, the strength of surround suppression was found to be significantly diminished by d amphetamine. The reduction in surround suppression was especially clear for bar lengths which exceeded the diameter of the control RF. No RF expansion was observed in the superficial layers of the SC when d-amphetamine was injected intravitreally. Furthermore, d-amphetamine had no discernable effect on the RF sizes of cells in the visual cortex. These results suggest that the RF changes in the SC were not of either retinal or cortical origin. We conclude that the mean retinal area which can potentially influence the activity of RFs in the superficial layers of the SC may be on average over 5 times greater than the RF area determined using conventional methods and criteria. These findings raise the interesting possibility that the relatively small size and sharp borders characteristic of RFs in the superficial layers arise from local inhibitory networks which delimit a broader field of excitatory activity supplied by retinal and cortical afferent terminals. Thus, in order to generate the RF changes observed here, either these local inhibitory circuits are amphetamine sensitive, or more likely, these inhibitory networks are dynamically modulated by an, as yet unidentified, amphetamine-sensitive input affecting visual RFs in the superficial layers. PMID- 8454010 TI - Changes in the electromyogram of two major hindlimb muscles during locomotor development in the rat. AB - The development of the electromyogram (EMG) of tibialis anterior (TA) and medial gastrocnemius (GM) during locomotion was studied in normal rats from the onset of quadruped walking (postnatal day 10, P10) until P42. The objectives were to relate signal properties of the EMG and coordination of muscle activity to functional development of the hindlimb, which proceeds rapidly around P15. Both the EMG characteristics and the activation pattern showed marked changes with age. Initially, the EMG bursts were irregular and protracted. The activity level in the two muscles, in particular in GM, seemed to be low. Until P14, the motor units of GM showed a tendency towards synchronization. The EMG of TA consisted of an adult-like interference pattern from the youngest age studied. Although co contraction of TA and GM was sometimes observed until P14, reciprocal activation of the muscles was evident at all ages. The timing of the alternating pattern became more accurate with age. The activity level in both muscles increased markedly from P15. These changes were reflected in the form factor (coefficient of variability) of the EMG and, to a lesser extent, in the power spectra. The time course of these changes bears a close temporal relationship to the development of locomotion. These results suggest that the degree of muscle activation is a decisive factor with respect to locomotor development. It is proposed that this is related to the maturation of supraspinal control. PMID- 8454011 TI - Simultaneous multi- and single-unit recordings in the rostral ventromedial medulla of ketamine-anaesthetized rats, and the cross-correlogram analysis of their interactions. AB - In anaesthetized rats, neurons located in the rostral ventromedial medulla (RVM) are classified by their differential responses to noxious stimulation. "On" cells are excited by noxious stimulation, "off" cells are inhibited and "neutral" cells are unaffected. Past research has primarily investigated the activity of these cells in lightly barbiturate anaesthetized animals while inducing a tail flick reflex. We recorded neuronal activity in the RVM of deeply ketamine-xylazine anaesthetized rats using a novel method of recording single- and multiunit activity simultaneously with one electrode. Under this anaesthetic paradigm we were able to record RVM cells which responded to noxious tail heating in the same manner as on and off cells without inducing a tail flick. A cross-correlogram analysis was done between the two levels of activity. It demonstrated that the RVM is a highly coordinated system in both the spontaneous period and the noxious evoked activity period. Through this technique it was also shown that both on and off cells fire simultaneously in the ketamine-xylazine paradigm. PMID- 8454012 TI - Characterization of hindlimb muscle afferents involved in ventilatory effects observed in decerebrate and spinal preparations. AB - Neurogenic changes of phrenic activity have previously been observed during periodic passive motions of one hindlimb in decorticate, unanaesthetized and curarized rabbit preparations before and after high spinal transection (Palisses et al. 1988). In decerebrate and spinal preparations, we aimed to determine, through rhythmic electrical stimulation of hindlimb muscle nerves, which muscle afferents are involved in these effects. In decerebrate preparations, these electrical stimulations (trains of shocks at 80 Hz for 300 ms every second for 20 s) produced ventilatory effects when group I + II afferent fibres of either flexor or extensor nerves were stimulated together and more powerful changes as soon as group III fibres were recruited. Stimulation of group I fibres alone induced no such effects. When present, these changes in respiratory activity consisted of a maintained decrease of the respiratory period due to both inspiratory and expiratory time shortening; in addition, the amplitude of the phrenic bursts greatly increased at the onset of electrical stimulation. After spinal transection at C2 level and pharmacological activation by nialamide and DOPA, only short-lasting phrenic bursts developed spontaneously; the electrical stimulation of group II and mainly group III flexor afferent fibres induced large amplitude phrenic activity whereas the stimulation of the same extensor afferents was relatively ineffective. The activation of phrenic motoneurones during group III flexor afferent stimulation was closely linked to each 300 ms period of stimulation. While the phrenic effects obtained in the spinal preparations by natural and by electrical periodic stimulation are quite similar to each other, those produced in decerebrate preparations differ substantially.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454013 TI - Pattern of extraocular muscle activation during reflex blinking. AB - Studies in humans and rabbits suggest that cocontraction of extraocular muscles occurs with reflex and voluntary blinks. We determined the pattern of extraocular muscle activity elicited by blink-evoking visual and trigeminal stimuli by electromyographically recording antagonistic pairs of extraocular muscles in alert rabbits. In addition, we recorded the activity of antidromically identified oculomotor motoneurons in response to the same stimuli in alert rabbits. The data demonstrate that all extraocular muscles except the superior oblique transiently increase their activity in response to blink-evoking stimuli. The pattern of extraocular muscle activity with reflex blinks mirrors that occurring in the lid closing muscle, orbicularis oculi, but the latency of extraocular muscle activation is longer. PMID- 8454014 TI - A role for the basal ganglia in nicotinic modulation of the blink reflex. AB - In humans and rats we found that nicotine transiently modifies the blink reflex. For blinks elicited by stimulation of the supraorbital branch of the trigeminal nerve, nicotine decreased the magnitude of the orbicularis oculi electromyogram (OOemg) and increased the latency of only the long-latency (R2) component. For blinks elicited by electrical stimulation of the cornea, nicotine decreased the magnitude and increased the latency of the single component of OOemg response. Since nicotine modified only one component of the supraorbitally elicited blink reflex, nicotine must act primarily on the central nervous system rather than at the muscle. The effects of nicotine could be caused by direct action on lower brainstem interneurons or indirectly by modulating descending systems impinging on blink interneurons. Since precollicular decerebration eliminated nicotine's effects on the blink reflex, nicotine must act through descending systems. Three lines of evidence suggest that nicotine affects the blink reflex through the basal ganglia by causing dopamine release in the striatum. First, stimulation of the substantia nigra mimicked the effects of nicotine on the blink reflex. Second, haloperidol, a dopamine (D2) receptor antagonist, blocked the effect of nicotine on the blink reflex. Third, apomorphine, a D2 receptor agonist, mimicked the effects of nicotine on the blink reflex. PMID- 8454015 TI - Effects of different types of mechanical load on the duration of the initial agonist pulse. AB - Ten right-hand-dominant subjects completed a series of unsighted, goal-directed, arm flexion movements under three different mechanical loading conditions: an inertial load, an elastic spring load, and a stretched-spring load. Subjects completed a series of inertial load training trials followed by random application of one of the three loads. Three time intervals of the first agonist pulse were considered for analysis: the time from initiation of agonist activity to the onset of movement, the interval from movement initiation to the end of the agonist pulse, and the duration of the entire agonist pulse. Analyses revealed that load type did not affect the duration of any of the time intervals studied. The results suggest the presence of a regulatory control process which temporally organizes an invariant agonist pulse even when the movement is perturbed by external loads possessing different mechanical characteristics. PMID- 8454016 TI - Separate populations of visually guided saccades in humans: reaction times and amplitudes. AB - The saccadic eye movements of 20 naive adults, 7 naive teenagers, 12 naive children, and 4 trained adult subjects were measured using two single target saccade tasks; the gap and the overlap task. In the gap task, the fixation point was switched off before the target occurred; in the overlap task it remained on until the end of each trial. The target position was randomly selected 4 degrees to the left or 4 degrees to the right of the fixation point. The subjects were instructed to look at the target when it appeared, not to react as fast as possible. They were not given any feedback about their performance. The results suggest that, in the gap task, most of the naive subjects exhibit at least two (the teenagers certainly three) clearly separated peaks in the distribution of the saccadic reaction times. The first peak occurs between 100 and 135 ms (express saccades), the second one between 140 and 180 ms (fast regular), and a third peak may follow at about 200 ms (slow regular). Other subjects did not show clear signs of two modes in the range of 100 to 180 ms, and still others did not produce any reaction times below 135 ms. In the overlap task as well three or even more peaks were obtained at about the same positions along the reaction time scale of many, but not all subjects. Group data as well as those of individual subjects were fitted by the superposition of three gaussian functions. Segregating the reaction time data into saccades that over- or undershoot the target indicated that express saccades almost never overshoot. The results are discussed in relation to the different neural processes preceding the initiation of visually-guided saccades. PMID- 8454017 TI - Asymmetry is present in the thalamofugal visual projections of female chicks. AB - Asymmetry of the thalamofugal visual projections of the chick has been previously reported to exist in males but not females. Using a larger sample size and a double-labelling procedure, projections to the visual Wulst were labelled with the retrograde tracers True Blue and Fluoro-gold and the ratio of contralateral projections to ipsilateral projections was calculated. We found that asymmetry does exist in female chicks, but to a lesser degree than in males. PMID- 8454018 TI - Horizontal canal input to upper cervical commissural neurons. AB - We studied in decerebrate, paralyzed cats, the effect of sinusoidal yaw rotation on upper cervical commissural neurons. The activity of some neurons was modulated by this stimulus, and they were classified as receiving input from the horizontal semicircular canal. The responses, which were mainly type II, were well correlated with the velocity of the stimulus. These commissural neurons, some of them propriospinal, transmit horizontal canal signals to the contralateral ventral horn, presumably to motoneurons, as well as to more caudal levels of the spinal cord. PMID- 8454019 TI - Detection of antigens in the urine of patients with acute Plasmodium vivax malaria. AB - Plasmodium antigens were detected by dot-blot assay in the urine of 50 patients infected with Plasmodium vivax. Antigens also were detected in 12/15 patients who no longer had detectable parasitemia, 3 weeks after chemotherapy. Antigenuria was negative 6 weeks after treatment. By Western blotting, four predominant protein antigens were identified in the urine of patients infected with P. vivax: 200, 180, 150, and 110 kDa. The dot-blot technique may prove to be a rapid and inexpensive method for diagnosing malaria in field studies and for clinical evaluation during chemotherapy. PMID- 8454020 TI - In vitro culture of the mosquito stages of Plasmodium falciparum. AB - The sporogonic cycle of Plasmodium falciparum was obtained in vitro. Mature gametocytes, from blood-stage cultures, produced gametes that underwent fertilization at elevated pH and ambient temperatures. Wheat germ agglutinin stimulated transformation of zygotes into retorts and ookinetes. Twenty-four hours thereafter, 18-49% mature ookinetes and 10-20% intermediate retort forms were counted. Cultures were seeded onto a basement membrane-like gel (Matrigel) in coculture with Drosophila melanogaster cells. Both ookinetes and retorts attached to Matrigel and transformed into oocysts. Mature oocysts and sporozoites expressed circumsporozoite protein. The entire life cycle of Plasmodium falciparum, the most important malaria pathogen of humans, can now be studied in vitro. PMID- 8454021 TI - Brugia pahangi: identification and characterization of an aminopeptidase associated with larval molting. AB - The third-stage larvae (L3) of the filarid parasite Brugia pahangi were surveyed for protease activity beginning with release from the mosquito vector through molting to the fourth-stage larvae (L4). A metalloaminopeptidase with a substrate preference for phenylalanine was released during the molting process. A screen of aminopeptidase inhibitors identified H-boroPhenylalanine-(pinacol) as highly effective, with a Ki of 1.3 x 10(-11) M. This peptidase inhibitor also arrested molting of L3 larvae in vitro at a concentration of 100 microM. PMID- 8454022 TI - Plasmodium falciparum: the immune response in rabbits to the clustered asparagine rich protein (CARP) after immunization in Freund's adjuvant or immunostimulating complexes (ISCOMs). AB - The Plasmodium falciparum clustered asparagine-rich protein (CARP) is a merozoite associated antigen which contains approximately 30% asparagine. Analysis of the DNA sequences located 5' of the cloned 1.4-kb CARP gene in the P. falciparum genome suggests that this gene fragment may encode the complete CARP and that the gene product is a protein of M(r) 50,000. To analyze the immunogenicity of CARP, the gene was expressed as a fusion protein with staphylococcal protein A (SpA CARP). Immunization of rabbits with SpA-CARP in Freund's complete adjuvant (FCA) resulted in a strong antibody response against CARP as measured in ELISA. This response was efficiently boosted and sustained over a long time while that induced by two immunizations with SpA-CARP in ISCOMs was weak and of shorter duration. In both instances, the antibody levels against CARP were further increased by a second booster injection consisting of either SpA-CARP or CARP fused to the serum albumin-binding region (BB) of streptococcal protein G (BB CARP) in PBS, indicating that immunizations with SpA-CARP in FCA or ISCOMs had induced a CARP-specific immunological memory. Boosting with BB-CARP in PBS was more efficient than boosting with SpA-CARP in PBS. In all rabbits, the antibodies obtained after the booster with CARP in PBS were the most efficient inhibitors of merozoite invasion in vitro. The antisera reacted with the intracellular parasite in immunofluorescence and with a band of M(r) 50,000 in immunoblotting while several high-molecular-weight components as well as the one of M(r) 50,000 were immunoprecipitated. The specificity of the antibody responses varied between the different rabbits as indicated in ELISA, with short synthetic peptides representing different CARP sequences. Taken together, the results suggest that a previously cloned genomic DNA fragment may encode the complete P. falciparum blood-stage antigen CARP and that CARP is immunogenic in rabbits both when administered in FCA or ISCOMs. PMID- 8454023 TI - A fluorescent peptide substrate for the surface metalloprotease of Leishmania. AB - A fluorescent oligopeptide substrate for the promastigote surface protease (PSP) of Leishmania was designed using the data reported for the substrate specificity of the enzyme (Bouvier, J., Schneider, P., Etges, R. J., and Bordier, C. 1990. Biochemistry 29, 10113-10119). The indole fluorescence of the tryptophan residue was efficiently quenched through resonance energy transfer by an N-terminal dansyl group located five amino acid residues away. The heptapeptide, dansyl-A-Y L-K-K-W-V-NH2, was cleaved by PSP between the tyrosine and leucine residues with a kcat/Km ratio of 8.8 x 10(6) M-1sec-1. Hydrolysis by the enzyme results in a time-dependent increase of fluorescence intensity of 3.7-fold. Assays can be designed based on the tryptophan fluorescence at 360 nm or by individual product analyses using thin-layer chromatography. The synthetic substrate is readily cleaved by the metalloprotease at the surface of fixed promastigotes. The specificity and sensitivity of such internally quenched fluorescent peptide substrate will facilitate the identification of novel inhibitors for the enzyme and aid in detailed studies on its enzymology. PMID- 8454024 TI - Brugia pahangi and Brugia malayi: a surface-associated glycoprotein (gp15/400) is composed of multiple tandemly repeated units and processed from a 400-kDa precursor. AB - The cuticle of filarial nematode parasites contains distinct and separable sets of soluble and structural proteins. Surface-labeling techniques have previously identified a soluble protein complex in adult stage Brugia which ranges in molecular weight from 15 to 200 kDa. Using an antiserum directed to the 15-kDa basal subunit of this complex, we show here that this complex is synthesized and processed from a single, very large precursor protein with a molecular weight of approximately 400 kDa. Molecular cloning, sequencing, and Southern analysis indicates that the protein is encoded by a single gene composed predominantly of approximately 20 tandemly repeated segments of 396 bp. The two complete copies of these repeated segments in our cDNA sequence are identical. Each subunit of 132 amino acids bears a consensus site for N-linked glycosylation, and glycosidase treatment indicates that this corresponds to an oligosaccharide side chain of 2 kDa. The protein displays no significant homology to sequences lodged in databases corresponding to molecules of known function. Nevertheless, a significant similarity (19/41 residues) is observed with the N-terminal sequence of a protein termed ABA-1, an allergen from Ascaris. PMID- 8454025 TI - Giardiavirus enters Giardia lamblia WB trophozoite via endocytosis. AB - As part of our continuing effort in the study of Giardiavirus life cycle, the early events of Giardia lamblia virus (GLV) infection in the trophozoites of G. lamblia WB strain were examined. Electron microscopy showed that GLV particles were initially localized on plasma membrane. As time progresses, GLV was translocated to the peripheral vacuole and then spread to the cytoplasm. Inhibitors of endocytosis such as sodium azide, chloroquine, or ammonium chloride disrupted viral infection when the drug was added simultaneously with the infecting GLV. The inhibitory effect was reduced when sodium azide or chloroquine was added at various intervals after infection. When cells infected for 1 hr were examined by immunofluorescence staining, sodium azide greatly reduced GLV staining signal in general while chloroquine restricted the staining signal to a few bright spots. Significantly more GLV was found in the peripheral vacuoles of chloroquine-treated cells than untreated controls by semiquantitative electron microscopy. In contrast, only a reduced amount of GLV was found in the peripheral vacuoles of sodium azide-treated cells. These results suggest that sodium azide reduces the internalization of infecting GLV, while chloroquine confines the virus in the peripheral vacuoles and, consequently, leads to nonproductive infection. We conclude from these observations that the entry of GLV into the susceptible WB cells in the event of infection is most likely mediated by endocytosis. PMID- 8454026 TI - Schistosoma mansoni: chromosomal localization of female-specific genes and a female-specific DNA element. AB - Two genes, p14 and p48, that are each expressed in a female-specific manner in vitelline cells in response to male pairing were each localized by in situ hybridization to chromosome 2. Biotinylated DNA was hybridized to target chromosomes and hybridization was detected using either alkaline phosphatase labeled avidin or fluorescein-labeled avidin. In addition Southern blots of genomic DNA separated by pulsed-field gradient gel electrophoresis was used to localize the genes to large chromosome fragments. p14 was localized to two EagI fragments (150 and 240 kb) found in the distal portion of the lower (q) arm of chromosome 2 in 79 of 109 metaphase preparations examined. p48 was localized to two EagI fragments (50 and 700 kb) found in the proximal portion of the lower arm of chromosome 2 in 52 of 63 metaphase preparations examined. A DNA repeat element, pW1, that hybridizes to genomic DNA from female but not male Schistosoma mansoni was also used as a hybridization probe. In all cells examined the biotinylated pW1 only hybridizes to a euchromatic gap region (eg3) within the large heterochromatin block of the long arm of the W chromosome. This specific hybridization coupled with the lack of chiasma formation in this region of the ZW bivalent (presumably due to heterochromatization) is offered as an explanation for the female-specific hybridization of pW1. PMID- 8454027 TI - Trichinella spiralis: the effect of oral immunization and the adjuvancy of cholera toxin on the mucosal and systemic immune response of mice. AB - The effect of oral immunization and the adjuvancy of cholera toxin (CT) were examined in mice infected with Trichinella spiralis. The mean of total muscle larvae was reduced by 36% in mice infected with Trichinella larvae in combination with CT. In mice fed soluble, particulate, or soluble/particulate antigens in combination with CT on Days 0, 14, and 21, and challenged with Trichinella larvae on Day 28, there was a significant reduction in adult worm fecundity (50%), worm size (20-30%), and the mean of total muscle larvae (75%) but no apparent effect on the rate of expulsion on Day 6 postchallenge. Following antigen feeding, but prior to challenge with Trichinella (Day 28), the immunoglobulin response was positive in only a small proportion of mice. On Day 6 following challenge with Trichinella larvae, the biliary immunoglobulin response was enhanced approximately 10-fold (P < 0.05) in all antigen-feeding treatments which included CT, compared with nonimmunized controls or antigen-feeding treatments which did not include CT. Similarly, the serum IgG response was enhanced following challenge with Trichinella larvae in treatments fed soluble, particulate, or soluble/particulate antigens with CT. The response was also enhanced in the particulate, but not in soluble or soluble/particulate antigen treatments without CT. PMID- 8454028 TI - Plasmodium vivax:recombination between potential allelic types of the merozoite surface protein MSP1 in parasites isolated from patients. AB - The merozoite surface protein MSP1, which is one of the most promising candidates for a malaria vaccine directed against erythrocytic stages, has been shown to be polymorphic in different malarial species. Characterization of the Plasmodium vivax MSP1 gene (Pv200) in two strains (Belem and Salvador-1) revealed the existence of several polymorphic regions. One of these regions has been examined here in primary parasite isolates obtained from patients in Sri Lanka. Oligonucleotide primers hybridizing to conserved parts of the gene on either side of a polymorphic region were used to amplify DNA from 22 isolates. Sequence analysis of the amplified portion of the MSP1 gene in five patients showed the existence of three types of polymorphic regions. Two were almost identical either to that of the Belem or to that of the Salvador-1 strain. The third polymorphic type appeared to have resulted from recombination between the two others. This recombination event took place inside a repeated part of the sequence. PMID- 8454029 TI - Brugia malayi: acquired resistance to microfilariae in BALB/c mice correlates with local Th2 responses. AB - The role of specific Th subsets in the regulation of acquired resistance to the filarial parasite Brugia malayi is not known. We examined pathologic and cytokine responses in filarial antigen-sensitized BALB/c mice inoculated intraperitoneally with live microfilariae. Animals immunized three times with soluble microfilarial antigen demonstrated accelerated clearance of live parasites (12 +/- 5% of parasites recovered from the peritoneal cavity 4 days after inoculation vs 57 +/- 6% in controls, P < 0.001). Elimination of microfilariae by immunized mice was associated with local eosinophilia (1.5 x 10(7) eosinophils/ml peritoneal wash fluid compared with 2 x 10(5) eosinophils/ml in unimmunized animals), development of local eosinophil-containing granulomas, and elevated serum IgE levels (7.0 +/- 1.4 vs 2.1 +/- 0.9 micrograms/ml in controls, P < 0.01). CD4+ cells from the site of parasite challenge produced Th2-associated cytokines exclusively (IL-4 and IL 5, not IFN-gamma and IL-2) in response to Brugia antigen, whereas spleen and lymph node cells produced both Th1- and Th2-associated cytokines. Mice immunized a single time with microfilarial antigen did not clear parasites in this time, and peritoneal exudate cells from these animals produced IFN-gamma but not IL-5. These results indicate that acquired resistance to B. malayi microfilariae in mice is associated with induction of a Th2 and not a Th1 response at the site of parasite elimination. PMID- 8454030 TI - Cryptosporidium parvum: culture in MDCK cells. PMID- 8454031 TI - Trypanosoma congolense: in vitro susceptibility of bloodstream forms to diminazene and isometamidium. PMID- 8454032 TI - Glycosyl phosphatidylinositols in Trypanosoma brucei. PMID- 8454033 TI - Intimal hyperplasia enhances myosin phosphorylation in rabbit carotid artery. AB - We examined physiological events in the hyperplastic artery, using a method based on the mechanical responsiveness and myosin light-chain phosphorylation in response to various stimulants. Six weeks after endothelial denudation by ballooning of the right carotid artery, strips of this artery with moderate intimal hyperplasia (intimal area was 30-50% of medial area in 20 of 28 rabbits) were used for experiments. Strips from the left carotid served as the normal control. When the hyperplastic artery was stimulated with 30 microM PGF2 alpha, the maximal tension (232.4 +/- 49.1 mg/mg dry wt, mean +/- SD) was significantly higher (P < 0.05) than that of the control (129.5 +/- 16.4 mg/mg). The maximal extent of myosin light-chain monophosphorylation (45.4 +/- 8.9%) and diphosphorylation (10.9 +/- 5.2%) in the hyperplastic artery was significantly higher (P < 0.05) than that in the control artery (33.0 +/- 4.8 and 4.0 +/- 4.8%, respectively). The monophosphorylation of the myosin light chain in the hyperplastic artery was sustained for up to 20 min, while that in the control artery decreased to the basal level within 20 min. Similar observations were obtained by stimulation with 60 mM K+ or 30 microM norepinephrine. Dose-response curves of the development of tension in the hyperplastic artery to various agonists (K+, PGF2 alpha, norepinephrine) shifted upward the curves for the control artery. These results suggest that qualitative changes in the characteristics of smooth muscle cells may occur in the intimal hyperplastic portion, including a hyperreactive contraction associated with enhanced and sustained phosphorylation of the myosin light chain. PMID- 8454034 TI - Production of cytokines belonging to the interleukin-8 family by human gingival fibroblasts stimulated with interleukin-1 beta in culture. AB - Three major neutrophil chemotactic peptides belonging to the interleukin-8 (IL-8) family were purified to homogeneity from the conditioned medium of the IL-1 beta stimulated human gingival fibroblasts culture. On the basis of their molecular masses and NH2-terminal amino acid sequences, these three neutrophil chemotactic factors were identical to melanoma growth stimulatory activity-alpha (MGSA/gro alpha), MGSA/gro-gamma and Ala-Val-Leu-Pro-Arg-IL-8 (AVLPR-IL-8), each belonging to the IL-8 family. It has been shown by the chemotaxis studies in vitro that the chemotactic activity of MGSA/gro-gamma is similar to that of MGSA/gro-alpha for both human and rat neutrophils, while AVLPR-IL-8 is chemotactic for human neutrophils but not for rat neutrophils. The in vitro findings were supported by the histological studies in vivo on the intradermal injection of either MGSA/gro alpha or AVLPR-IL-8 into the back of the rats. The results obtained in the present experiment suggest that human gingival fibroblasts play an important role in gingival inflammation through the production of neutrophil chemotactic factors newly characterized as the IL-8 family in response to inflammatory chemical mediators including IL-1 beta. PMID- 8454035 TI - Human neonatal and adult vascular smooth muscle cells in culture. AB - Neonatal vascular smooth muscle cells (SMC) in culture have been demonstrated to be quite different from adult SMC and to be similar to intimal SMC in animal models. To characterize human neonatal vascular SMC in culture, cultures of arterial SMC were prepared by an explant method from the subclavian arteries of autopsied patients (10 adults and 6 neonates). The morphology and growth characteristics of these cells were compared. All cells were positively immunostained with HHF 35, a monoclonal antibody specific for muscle actin. Electron microscopically, both adult and neonatal SMC were of synthetic phenotype. SMC from neonates had a short population doubling time (PDT, 28.6 +/- 7.5 hr) and high saturation density (SD, 37.5 +/- 11.9 x 10(4) cells/cm2). They did not show hill and valley growth patterns. Among the SMC cultured from adult media, two subtypes were distinguished, based on their growth characteristics. Classical adult SMC (7 of 10 cases) grew in hill and valley patterns with long PDT and low SD values (61.7 +/- 28.8 hr, 6.5 +/- 1.9 x 10(4) cells/cm2, respectively). The second subtype (3 of 10 cases), neonatal-type adult SMC, had PDT and SD values (22.9 +/- 4.0 hr, 31.3 +/- 14.7 x 10(4) cells/cm2, respectively) similar to those of neonatal SMC. Intimal SMC became senescent in early phases of subculture. To test for the possible participation of autocrine growth factors in the heterogeneity of the growth patterns, Northern blot analysis was conducted for PDGF-A, TGF-beta, c-myc, and c-fos mRNA in three types of SMC. There was no significant difference in these mRNA levels between the SMC. We demonstrated that human neonatal vascular SMC in culture are quite different in their growth characteristics from classical adult SMC in culture and that neonatal-type SMC can be isolated from adult media. PMID- 8454036 TI - Body fat and fat distribution by anthropometry and the response to high-fat cholesterol-containing diet in monkeys. AB - Considerable variability exists among individuals in the response of plasma cholesterol to changes in dietary fat and cholesterol, and obesity is one variable reported to affect this response. This study was performed to determine the relationship between body fat and changes in plasma cholesterol in cynomolgus monkeys fed a high-fat cholesterol-containing diet for 12 months. The animals gained significant body weight (body mass index increased from 30.5 +/- 0.5 to 35.7 +/- 2.8 kg/m2) and skinfold parameters of body fat increased as well. Total cholesterol increased from 109 +/- 4 to 390 +/- 25 mg/dl (P < 0.001), and there were also significant increases in LDL- and HDL-cholesterol and triglyceride. While there was very little relationship between body fat and plasma lipids before the diet, after 12 months, there were significant negative correlations between total and LDL-cholesterol and anthropometric measures of body fat (r ranged from -0.37 to -0.55, P < 0.01). The correlations were not affected when the effects of baseline body mass index and serum cholesterol and total food intake were controlled by partial correlation analysis. In this sample of animals, the acquisition of greater body fat appeared to protect against rises in cholesterol in response to consumption of a high-fat cholesterol-containing diet. PMID- 8454037 TI - Effect of ethanol on cytochrome P450 2E1 (CYP2E1), lipid peroxidation, and serum protein adduct formation in relation to liver pathology pathogenesis. AB - It is well established that chronic ethanol ingestion enhances lipid peroxidation in the liver in vivo and in vitro. The relationship of lipid peroxidation and protein adduct formation to morphologically assessed liver damage remains problematic. To help determine if a relationship exists between lipid peroxidation and liver pathology rats were fed ethanol and a high fat diet by continuous intragastric tube feeding for 72 days, maintaining the blood alcohol levels above 200 mg/dl. This model induced a fatty liver with focal necrosis and fibrosis. This pathology was associated with an increased total cytochrome P450, an increased cytochrome P450 2E1 isoenzyme (CYP2E1), a decrease in the NADPH cytochrome P450 reductase activity, an increased rate of NADPH oxidation and an increased NADPH-dependent lipid peroxidation in liver microsomes compared to controls. Serum protein adducts with malondialdehyde 4-hydroxynonenal were significantly increased. Thus, the alcohol-induced liver pathology was associated with the induction of CYP2EI, lipid peroxidation, and protein adduct formation. When isoniazid (INH) in therapeutic doses was fed to rats with ethanol these parameters were changed in that central-central bridging fibrosis was increased, as was lipid peroxidation, whereas INH reduced the ethanol-induced decrease in the reductase, the increase in total P450 and CYP2EI, as well as the NADPH oxidation rate and the elevation of serum transaminase levels. The results tend to link central-central bridging fibrosis with increased lipid peroxidation and aldehyde-protein adduct formation caused by ethanol. PMID- 8454038 TI - Tyrosine kinase activity is involved in the protein kinase C induced expression of interleukin-1 beta gene in monocytic cells. AB - The role of protein tyrosine kinases in the expression of interleukin-1 beta (IL 1 beta) gene in response to phorbol esters (PMA) in THP-1 cell line was investigated. Genistein, a specific tyrosine kinase inhibitor, inhibited PMA induced IL-1 beta protein and mRNA levels in THP-1 cells. Genistein did not have a significant effect on PMA induced activity in transient transfection assays using reporter gene constructs containing the PMA responsive sequence of the IL-1 beta gene linked to IL-1 beta promoter, or five repeats of PMA responsive sites (AP-1 sites) in front of a thymidine kinase promoter. This indicates that the tyrosine kinase activity required for the PMA induced IL-1 beta expression is coupled downstream from or functions independent of the PMA induced AP-1 activity. PMID- 8454039 TI - Cloning of two isoforms of the rat brain Na(+)-Ca2+ exchanger gene and their functional expression in HeLa cells. AB - Two functional isoforms of the rat brain Na(+)-Ca2+ exchanger were isolated from a lambda ZAP hippocampus cDNA library. The open reading frame of clone RBE-1 codes for a protein 935 amino acids long, and that of clone RBE-2 codes for a protein 958 amino acids long. Expression HeLa cells of Na+ gradient dependent Ca2+ transport activity was determined following transfection of the cells with either RBE-1 or RBE-2. Both clones expressed proteins that exchange Na+ with Ca2+ in an electrogenic manner and none of them exhibited a dependency of the antiport on K, since they transported Ca2+ in an Na+ gradient dependent manner in external choline chloride as well. PMID- 8454040 TI - Farnesylcysteine analogues inhibit chemotactic peptide receptor-mediated G protein activation in human HL-60 granulocyte membranes. AB - Analogues of S-prenylated cysteine like N-acetyl-S-trans,trans-farnesyl-L cysteine (AFC) have previously been shown to inhibit the carboxyl methylation of proteins carrying a C-terminal S-prenylated cysteine residue and to block the endotoxin-activated serum-elicited chemotactic response of mouse macrophages. Here, we show that AFC inhibits both basal and formyl peptide receptor-stimulated binding of guanosine 5'-O-(3-thiotriphosphate) (GTP[S]) to and hydrolysis of GTP by membranes of myeloid differentiated HL-60 granulocytes. Receptor-stimulated GTP[S] binding and GTP hydrolysis are more sensitive to AFC inhibition than basal G-protein functions. Inhibition of formyl peptide receptor-mediated G-protein activation is also observed for S-trans,trans-farnesyl-3-thiopropionic acid, but not for N-acetyl-S-trans-geranyl-L-cysteine, N-acetyl-L-cysteine, or the methyl ester of AFC, suggesting that the farnesyl moiety and the carboxyl group, but not the peptide bond of AFC are required for inhibition. The observations that exogeneous S-adenosyl-L-methionine is apparently not required for and S-adenosyl L-homocysteine does not attenuate the inhibitory action of AFC raise the distinct possibility that AFC inhibits receptor-mediated G-protein interaction by a mechanism other than inhibition of protein carboxyl methylation. PMID- 8454041 TI - A 5 kDa protein (SCS23) from the 30 S subunit of the spinach chloroplast ribosome. AB - The proteins of the 30 S ribosomal subunits from spinach chloroplasts were investigated using a radical-free and highly reducing (RFHR) method of two dimensional polyacrylamide gel electrophoresis (PAGE). Twenty-three proteins were resolved on the gel down to the smallest protein of 5 kDa. The N-terminal amino acid sequence of the 5 kDa protein showed no homology with that of any other protein stored in databases, and the copy numbers were estimated to be 0.88 +/- 0.16 and 0.72 +/- 0.04 in the 30 S subunits and the 70 S ribosomes, respectively. The results suggest that the 5 kDa protein, which we have called SCS23, may be an essential ribosomal protein specific to spinach chloroplasts. PMID- 8454042 TI - A conformation-dependent monoclonal antibody against active chicken acetylcholinesterase. AB - We show that the C-131 monoclonal antibody, directed against chicken AChE, recognizes active chicken AChE, but not the SDS-denatured or heat-inactivated protein. Previous results indicated that C-131 only binds to the active enzyme, and not to inactive molecules which also occur in the embryonic chicken brain. In contrast with C-131, other monoclonal antibodies obtained in the same series, such as C-6 and C-54, also recognize denatured or inactive AChE. It is noteworthy that these antibodies all seem to react with a trypsin-sensitive peptide which is present in chicken but not in mammalian or Torpedo AChE, whereas the C-131 antibody binds trypsin-modified as well as intact molecules. These results show that C-131 is highly conformation-dependent, specific for active AChE. They confirm our previous conclusion that active and inactive molecules arise from different folding processes. PMID- 8454043 TI - The projection structure of perfringolysin O (Clostridium perfringens theta toxin). AB - The cytolysin Perfringolysin O was applied to lipid layers and the obtained ring shaped oligomers analyzed by electron microscopy and image processing. The final result shows the periodic repeat of 2.4 nm along the outer rim of the ring. The asymmetric protein unit, corresponding to one monomer, spans the ring from the convex to the concave surface. It shows a clear protein peak close to the outer radius and less density in the middle of the oligomer. The number of monomers in the average ring is 50, and the inner radius of the aggregate is approximately 15 nm. PMID- 8454044 TI - Sulfhydryl oxidation induces rapid and reversible closure of the ATP-regulated K+ channel in the pancreatic beta-cell. AB - Effects of sulfhydryl modification on the ATP regulated K+ channel (KATP channel) in the pancreatic beta-cell were studied, using the patch clamp technique. Application of the sulfhydryl oxidizing agents thimerosal and 2,2'-dithio-bis(5 nitropyridine) (DTBNP), in micromolar concentrations, caused complete inhibition of the KATP channel, in inside-out patches. The inhibition was rapid and was reversed by the disulfide reducing agents dithiothreitol and cysteine. Thimerosal, which is poorly membrane permeable, inhibited channel activity, only when applied to the intracellular face of the plasma membrane. In contrast, DTBNP, which is highly lipophilic, caused closure of the KATP channel and consequent depolarization of the membrane potential, also when applied extracellularly. Our results indicate the presence of accessible free SH groups on the cytoplasmic side of the KATP channel in the pancreatic beta-cell. These SH groups are essential for channel function and it is possible that thiol-dependent redox mechanisms can modulate KATP channel activity. PMID- 8454045 TI - Evidence for binding of extrachromosomal DNA sequences to nuclear matrix proteins in multidrug-resistant KB-V1 cells. AB - Multidrug-resistant KB-V1 cells carry amplified mdrl gene sequences located in an extrachromosomal compartment (on episomes). Since episomes do not contain centromeric or telomeric sequences it is unclear whether they are able to bind to nuclear matrix proteins that may regulate episomal gene expression. Using high salt treatments followed by in situ hybridization and dot blot analyses we found evidence for direct binding of episomal DNA to nuclear matrix proteins. This binding could only be reversed after incubation with trypsin or proteinase K as determined by contour-clamped homogeneous electric field (CHEF) electrophoresis. Our findings are consistent with the concept that circular extrachromosomal DNA may not only reintegrate into nuclear DNA but may also be subject to functional control by regulatory proteins within the nuclear matrix. PMID- 8454046 TI - Nucleotide sequence of cDNA encoding the fire ant venom protein Sol i II. AB - For the first time the cDNA encoding a fire ant venom protein has been sequenced. Oligonucleotides were designed according to the amino acid sequence. The cDNA sequence was obtained by hybridizing these primers to mRNA and enhancement by the PCR technique. Comparison to the amino acid sequence of the venom protein shows a leader sequence 19 amino acids long. PMID- 8454047 TI - Comparison of phospholipase D activity in vasopressin- and phorbol ester stimulated fibroblasts. AB - Phospholipase D (PLD) activation by vasopressin (VP) was compared to activation by TPA in REF52 cells prelabeled with [3H]glycerol and [14C]myristic acid. Upon VP-treatment, the formation of [3H] and [14C]phosphatidic acid (PA) and phosphatidylethanol (PEt) was accompanied by the loss of radioactivity from PC and PI. However, upon TPA-treatment, radioactivity was lost from PC only. No significant changes of phosphatidylethanolamine and phosphatidylserine were detected in the same samples. The inclusion of 5 microM staurosporine for 10 min diminished the production of [3H]PEt and [14C]PEt by 27% and 53% in VP-treated cells, and by 100% and 75% in TPA-treated cells, respectively. Adding 1 mM EGTA to chelate extracellular Ca2+ inhibited [3H]PEt by approximately 31% and [14C]PEt by 17% after VP-stimulation. In contrast, EGTA had no effect on TPA-stimulation. The data suggest that REF52 cells contain dual PLD activities. The first is stimulated only by VP, requires Ca2+ and hydrolyzes PI. The second is stimulated by both TPA and VP, activated by protein kinase C and hydrolyzes PC. PMID- 8454048 TI - Myoglobin protects against endothelial cell membrane damage associated with hydrogen peroxide or xanthine/xanthine oxidase. AB - Oxymyoglobin at 'physiological' concentrations of 20-100 micromolar protected cultured endothelial cells from damage by xanthine/xanthine oxidase or by hydrogen peroxide. Metmyoglobin also provided a degree of protection, but apomyoglobin was ineffective. Protection was enhanced in the presence of ascorbate (0.01-1 mM). Myoglobin may have a physiological role in the protection of muscular tissue from ischaemia/reperfusion-induced damage. PMID- 8454049 TI - Imidazole antimycotics inhibitors of cytochrome P450 increase phosphatidylserine synthesis similarly to K(+)-channel blockers in Jurkat T cells. AB - The imidazole antimycotics, miconazole, econazole and triclomazole as well as alpha-naphtoflavone, known as powerful inhibitors of cytochrome P450 and previously recognized as K+ channel blockers are shown to be potent activators of the base exchange enzyme system responsible for the biosynthesis of phosphatidylserine in Jurkat T cells. The inhibition of CD3-induced Ca2+ influx by antimycotics but not by K+ channel blockers, demonstrated that the rise in phosphatidylserine synthesis caused by the two classes of drugs, was independent of Ca2+ influx in the cells. In addition, we show that the action of these drugs on phosphatidylserine synthesis was not mimicked by modifications of membrane potential. The regulation of both K+ channels and the base exchange enzyme system thus occurs through a similar (or common) pathway that is independent of Ca(2+) influx and membrane potential. PMID- 8454050 TI - Identification of CpG island at the 5' end of murine leukemia inhibitory factor gene. AB - We identified a CpG island at the 5' end of murine leukemia inhibitory factor gene (LIF). The CpG island is 0.6 kb long and covers most of the first exon and first intron. The region is non-methylated, its G+C content is 65% and relative frequency of CpG dinucleotide is 0.7. The block of 150 nucleotides, which is 72% conserved between murine, human, ovine and porcine genes, is a part of the CpG island. Two DNA fragments from this CpG island interact with nuclear proteins from NIH 3T3 cells. One fragment partially covers the block of conserved nucleotides. Human, ovine and porcine LIF genes also contain G+C- and CpG-rich sequences in the corresponding region. PMID- 8454051 TI - Expression and binding properties of two isoforms of the human growth hormone receptor. AB - Two isoforms of the human growth hormone receptor mRNA, one containing exon 3 (encoding an extracellular domain of the receptor), hGHR, and one excluding exon 3, hGHRd3, have been described. To study the cellular distribution of the two types of messengers we have analysed a panel of tissues. Both isoforms were expressed independently or simultaneously depending on the tissue studied. To investigate the binding properties of hGHRd3 we have cloned its cDNA in a eukaryotic expression vector; transient expression in COS-7 cells showed that the receptor without exon 3 was expressed on the plasma membrane and was able to bind human growth hormone (hGH) with the same high affinity as hGHR. Human lactogen (hCS) removed 125I-hGH bound to the full-length and exon 3-excluding receptors to the same extent. These results show that hGHR and hGHRd3 have tissue-specific expression and share identical binding properties for hGH and hCS and leave open the possibility that exon 3 might influence receptor signalling. PMID- 8454052 TI - Molecular cloning of the human alpha 2(IX) collagen cDNA and assignment of the human COL9A2 gene to chromosome 1. AB - Type IX collagen, a heterotrimer of alpha 1(IX), alpha 2(IX) and alpha 3(IX) chains, is a cartilage-specific fibril-associated collagen. In the process of characterizing genomic clones for the mouse alpha 2(IX) collagen gene four pairs of oligonucleotide primers designed for amplification of murine exon sequences were also utilized to construct cDNA clones for human alpha 2(IX) collagen spanning > 90% of the coding region. The amino acid and nucleotide sequence identities between human and chick are 78% and 71%, respectively. Localization of the COL9A2 gene to human chromosome 1 was subsequently performed using a panel of DNAs from human/rodent somatic cell hybrids. PMID- 8454053 TI - Human gamma-interferon expression in the mammary gland of transgenic mice. AB - Transgenic mice carrying a hybrid gene consisting of ovine beta-lactoglobulin gene sequences and human gamma-interferon (hIFN-g) cDNA were produced. hIFN-g expression in the mammary gland of two lactating transgenic founder females was found. The concentration of active hIFN-g in the milk was estimated as being ca. 1800 IU/ml. The hIFN-g ability to express in the mammary gland was found in the progeny of transgenic founder male. PMID- 8454054 TI - Participation of the overproduced elongation factor Tu from Thermus thermophilus in protein biosynthesis of Escherichia coli. AB - The influence of the overproduced elongation factor Tu (EF-Tu) from Thermus thermophilus on the protein biosynthesis in Escherichia coli was investigated both in vivo and in vitro. A kirromycin-resistant E. coli strain became sensitive to this antibiotic upon the expression of the tuf A-gene of T. thermophilus present on a plasmid. In in vitro translation with components of the kirromycin resistant E. coli strain the poly(Phe) synthesis stopped when minute amounts of the EF-Tu from T. thermophilus were added. Both results indicate the sensitivity of the T. thermophilus EF-Tu to kirromycin and its participation in the polypeptide synthesis of E. coli. PMID- 8454055 TI - NMR and circular dichroism studies of the lantibiotic nisin in non-aqueous environments. AB - The lantibiotic, nisin, which is known to interact with membranes of certain Gram positive bacteria, was studied in three model systems which mimic a membrane-like environment, i.e. a mixture of trifluoroethanol and water, or micelles of sodium dodecyl sulfate or dodecylphosphocholine. The 1H NMR spectra of nisin in the non aqueous environments, at 40 degrees C and pH 3.5, have been assigned completely. The CD and NMR results indicate that the conformation of nisin in the three non aqueous environments differs from that in aqueous solution, and that the conformation in the two micellar systems is similar. The major conformational changes, relative to nisin in aqueous solution, occur in the N-terminus. PMID- 8454056 TI - Reconstitution of functional muscarinic receptors by co-expression of amino- and carboxyl-terminal receptor fragments. AB - Truncated m2 and m3 muscarinic receptors (referred to as m2- and m3-trunc), containing transmembrane domains I-V and the N-terminal portion of the third cytoplasmic loop, were co-expressed in COS-7 cells with the corresponding C terminal receptor fragments (referred to as m2- and m3-tail; containing transmembrane domains VI and VII). Expression of any of these four polypeptides alone did not result in any detectable [3H]N-methylscopolamine ([3H]NMS) binding activity. However, specific [3H]NMS binding sites were observed after co expression of m2-trunc with m2-tail and m3-trunc with m3-tail. These sites displayed ligand binding properties similar to those of the two wild-type receptors. The 'reconstituted' m3-trunc/m3-tail receptor was also able to stimulate agonist-dependent phosphatidyl inositol hydrolysis in a fashion similar to the wild-type m3 receptor, whereas all other polypeptide combinations were inactive. These data suggest that muscarinic receptors are assembled in a fashion analogous to two-subunit receptors. PMID- 8454057 TI - Effects of fatty acid oxidation on glucose utilization by isolated hepatocytes. AB - We have studied the inhibitory action of long- and short-chain fatty acids on hepatic glucose utilization in hepatocytes isolated from fasted rats. The rates of hepatic glucose phosphorylation and glycolysis were determined from the tritiated products of [2-3H] and [6-3H]glucose metabolism, respectively. The difference between these was taken as an estimate of the 'cycling' between glucose and glucose-6-phosphate. In the presence of 40 mM glucose this cycling was estimated at 0.68 mumol/min/g wet wt. Glucose phosphorylation was unaffected during palmitate and hexanoate oxidation to ketone bodies but glycolysis was inhibited. The rate of glucose cycling was increased during this phase to 1.25 mumol/min/g. Following the complete metabolism of the fatty acids, glycolysis was reinstated and cycling rates returned to control levels. Hepatic glucose cycling appears to be an important component of the glucose/fatty acid cycle. PMID- 8454058 TI - The phorbol derivatives thymeleatoxin and 12-deoxyphorbol-13-O-phenylacetate-10 acetate cause translocation and down-regulation of multiple protein kinase C isozymes. AB - Phorbol esters such as phorbol 12-myristate,13-acetate (PMA) are potent activators of protein kinase C (PKC), and activate all PKC isozymes except zeta and lambda. Recently, 12-deoxyphorbol-13-O-phenylacetate-20-acetate (dPPA) and thymeleatoxin (Tx) were reported to selectively activate PKC beta 1 (dPPA) and PKC alpha, -beta, and -gamma (Tx), but not PKC delta or PKC epsilon in vitro. We examined the ability of these phorbol derivatives to translocate and down regulate PKC isozymes in intact cells. Our findings demonstrate that dPPA and Tx cause translocation and down-regulation of multiple PKC isozymes, including delta and epsilon. PMID- 8454059 TI - Iron released from an erythrocyte lysate by oxidative stress is diffusible and in redox active form. AB - The incubation of a ghost-free erythrocyte lysate with the oxidizing agent phenylhydrazine resulted in both methemoglobin formation and release of iron in a desferrioxamine (DFO)-chelatable form. The released iron was diffusible, as shown by a dialysis carried out simultaneously with the incubation. When the dialysate was added to erythrocyte ghosts or to microsomes from liver or brain, lipid peroxidation developed in the membranes, indicating that the diffusible iron was in a redox active form. The addition of ATP to the lysate markedly increased both iron diffusion and lipid peroxidation in the membranes subsequently added to the dialysate. The possible implication of these data in some well known pathologies is discussed. PMID- 8454060 TI - Rainbow trout ovarian cholesterol side-chain cleavage cytochrome P450 (P450scc). cDNA cloning and mRNA expression during oogenesis. AB - A cDNA clone encoding cholesterol side-chain cleavage cytochrome P450 (P450scc) was isolated from a rainbow trout ovarian follicle cDNA library. The cDNA contains an open reading frame of 1,542 nucleotides encoding a protein of 514 amino acids. The predicted amino acid sequence of trout P450scc shows 48% homology with that of human, and 46% homology with that of rat, bovine and pig. P450scc activity was confirmed by transfected COS-1 monkey kidney tumour cells with an expression vector for trout P450scc cDNA and subsequent detection of conversion from 25-hydroxycholesterol to pregnenolone by radioimmunoassay. The cDNA only hybridized to a single 1.8 kb RNA transcript. The transcript was not found in early vitellogenic follicles, barely detected in postvitellogenic follicles, and abundant in postovulatory follicles. PMID- 8454061 TI - Procathepsin D cannot autoactivate to cathepsin D at acid pH. AB - The amino acid sequence of the propart of bovine procathepsin D was determined at the protein level. Incubation of the isolated procathepsin D at pH 3.5-5.0 for 30 120 min leads to a 2 kDa reduction in its molecular mass, as seen by SDS-PAGE. The activation product is pseudocathepsin D and is the result of a proteolytic cleavage between LeuP26 and IleP27 in the propart. Incubation at pH 5.0 for 20 h of either procathepsin D or pseudocathepsin D results in both cases in approximately equal amounts of pseudocathepsin D and a further processed intermediate, nine amino acids shorter than pseudocathepsin D. No reaction products corresponding to cathepsin D with a mature amino terminus were observed, showing that autoproteolysis alone cannot generate the mature form found in the lysosomes. PMID- 8454062 TI - Purification and characterization of a 90 kDa protein released from human tumors and tumor cell lines. AB - A novel tumor-associated protein, termed 90K, and recognized by mAb SP-2 was purified from serum of breast cancer patients, ovarian cancer ascitic fluid and conditioned medium of human breast cancer cells. In these three sources, native 90K is present as a high molecular weight complex that was dissociated by SDS PAGE into a major band of approximately 90,000 Da. On the basis of electrophoretic mobility, buoyant density value, amino acid composition, and immunoreactivity, the 90K from the different sources appeared to be identical. NH2-terminal amino acid sequence revealed no homology to known protein. PMID- 8454063 TI - A protein histidine kinase induced in rat liver by peroxisome proliferators. In vitro activation by Ras protein and guanine nucleotides. AB - A novel protein kinase is induced in rat liver plasma membrane by the administration of peroxisome proliferators. A 36 kDa protein (P36) on the membrane was rapidly phosphorylated in vitro by the kinase and the phosphorylated amino acid was identified as phosphohistidine. Histidine phosphorylation of P36 was activated in vitro by recombinant Ras protein and GTP; both decreased Michaelis constant (Km) for ATP from 1.25 to 0.25 microM. The novel histidine kinase, products of which have been overlooked due to their acid lability, may participate in cellular signaling and peroxisome proliferators may perturb the pathway. PMID- 8454064 TI - Cloning and sequencing of glutamate mutase component E from Clostridium tetanomorphum. AB - The nucleotide sequence of the large subunit E of glutamate mutase of Clostridium tetanomorphum was determined. The protein consists of 483 amino acids and is not made in a precursor form, thus excluding the possibility of subunit E being a pyruvoyl enzyme. It shows no homology to any other protein in the database, and while binding coenzyme B12, a conspicuous B12 binding motif, shared amongst other proteins, is not detectable at the sequence level. PMID- 8454065 TI - Effect of site-directed mutagenesis on conserved positions of Drosophila alcohol dehydrogenase. AB - Tyr152 and Lys156 may be functionally important residues in Drosophila ADH as they are conserved in the genus and in all short-chain dehydrogenases. In addition, unaltered Gly positions could have a crucial role in the building of the structural framework. We have modified Drosophila ADH and expressed the mutant forms in E. coli. Mutation of Tyr152 to Glu or Gln, Lys156 to Ile, Gly184 to Leu, and the double mutant Gly130 to Cys and Gly133 to Ile, all rendered, with different substrates and at different pHs, an inactive enzyme. Results suggest that Tyr152 and Lys156 are involved in catalysis and that Gly130, Gly133 and Gly184 contribute substantially to the structure of the active form. PMID- 8454066 TI - TGMV replication protein AL1 preferentially binds to single-stranded DNA from the common region. AB - The AL1 protein of tomato golden mosaic virus (TGMV) is encoded by the viral DNA and has been shown to be essential for viral DNA replication. We have over expressed the AL1 open reading frame in E. coli and purified the protein from bacterial extracts to near homogeneity. Using various different techniques we have studied the interaction of the AL1 protein with DNA. The AL1 protein is able to bind to DNA containing the common region of the viral genome, which can be demonstrated by photochemical cross-linking. Binding is 4-fold stronger to single stranded than to double-stranded DNA. Antibodies against the AL1 protein can be used to precipitate the protein-DNA complex. The binding to single- and double stranded DNA is specifically to the common region since a DNA fragment unrelated to TGMV is not shifted in a gel retardation assay. PMID- 8454067 TI - Why do vascular specialists need to understand epidemiology? PMID- 8454068 TI - Inflammatory aneurysm causing urinary extravasation. PMID- 8454069 TI - Ruptured balloon separation during percutaneous transluminal renal artery angioplasty. AB - A rare complication of percutaneous transluminal renal artery angioplasty is reported. Separation of a ruptured balloon was followed by embolism and acute limb ischaemia requiring emergency surgery. Both the renovascular hypertension and the complication of angioplasty were treated successfully. This case illustrates the need for close collaboration between interventional radiologists and vascular surgeons. PMID- 8454070 TI - Impedance analysis versus colour Duplex in femorodistal vein graft surveillance. AB - Fifty patients who have undergone femorodistal bypass surgery have been followed up using impedance analysis and colour Duplex, with biplanar intraarterial digital subtraction angiography being used as the arbiter to define "at risk" grafts. An impedance score of 0.49 (0.43-0.55) was found in the "at risk" grafts, all of which underwent an interventional procedure compared to 0.39 (0.36-0.42) (p = 0.003, Mann-Whitney U test) in those with no problem. In total, 166 examinations were performed. The sensitivity and specificity were all greater than 91% when compared to angiography. Impedance analysis is simple, non invasive, easy to perform and it takes only 10 min to complete the examination. In view of the results obtained using impedance analysis in comparison with Duplex scanning, we suggest that non-invasive impedance is a suitable alternative to colour Duplex for graft surveillance (mean +95% confidence interval). PMID- 8454071 TI - The histopathology of infrainguinal vein graft stenoses. AB - The precise histopathological nature of vein graft stenoses is unclear. Some authors have suggested that these lesions are due to intimal hyperplasia and others have claimed that they are fibrous strictures. The aim of this study was to determine the histological nature of infrainguinal vein graft stenoses by examining sections of vein grafts that had developed stenoses and had been surgically revised. This was performed using a combined anti-smooth muscle actin/Millers elastin stain. The results show that vein graft stenoses are due to intimal hyperplasia whereby smooth muscle cells proliferate and cause thickening of the intimal layer. PMID- 8454072 TI - Infrapopliteal angioplasty for limb salvage. AB - Fourteen infrapopliteal angioplasties were performed in 13 patients with critical limb ischaemia. Clinical indications were rest pain, ulceration, gangrene or a critically ischaemic limb from a graft occlusion secondary to an infrapopliteal lesion. The average ankle-brachial ratio was 0.22 in non-diabetics. Technical success was achieved in all lesions with an average increase of Doppler ratios of 0.5. Of the 13 patients, 11 (85%) showed early clinical improvement (with average length of follow-up of 8 months, range 1-18 months). With the introduction of smaller lower profile catheters, hydrophilic and steerable wires and the advent of digital subtraction angiography, infrapopliteal angioplasty can now be performed successfully and with few complications. The presence of spasm should be aggressively treated with intra-arterial nitroglycerin or verapamil. PMID- 8454073 TI - PTFE bypass grafting to isolated popliteal segments in critical limb ischaemia. AB - Although the quality of the distal run-off has been considered as an important factor affecting the success of bypass grafting, reasonable results have nevertheless been reported for bypass grafts to a popliteal artery with no direct communication with the tibial or peroneal vessels (isolated popliteal segment, IPS). The use of autogenous vein has produced the best results in this situation with most authors finding polytetrafluoroethylene (PTFE) less satisfactory. Improved results have nevertheless been shown for femoropopliteal and femorotibial PTFE grafts by the incorporation of vein patches into the anastomoses. In this paper, the influence of this technique on the patency of PTFE grafts to IPS is evaluated. Thirty-three PTFE grafts to an IPS and 67 to the below knee (BK) popliteal artery with one or more run-off vessels were studied. All IPS grafts were carried out for limb salvage and in the BK popliteal group, 46 (69%) were for limb salvage and 21 (31%) were for severe claudication. Groups were matched in terms of age, smoking history and prevalence of diabetes mellitus. Cumulative patency rates of 84% at 1 year and 76% at 3 years were achieved in the IPS group compared to 90 and 81% for the BK popliteal group with one or more run-off vessels. Using the Taylor patch technique, comparable 3 year patency rates can be expected for PTFE grafts to IPSs and to BK popliteal arteries with patient tibial or peroneal run-off. PMID- 8454074 TI - Who doesn't need vascular medicine?--A team approach to vascular care and the role for vascular medicine. PMID- 8454075 TI - Long-term results of double-balloon percutaneous transluminal angioplasty of the aorta and iliac arteries. AB - Seventy-nine patients have been treated by double-balloon percutaneous transluminal angioplasty for aortoiliac atherosclerotic lesions within 0.5 cm of the aortic bifurcation. Seven patients had repeated angioplasties, a total of 86 procedures over an 8 year period up to December 1990. The technique is described and its merits discussed. Technically successful dilatation was achieved in 81 cases (94%) and symptomatic relief was obtained in 75 (87%), including 12 of 14 patients with critical ischaemia. Fourteen of 17 occlusions up to 6 cm long and 67 of 69 stenoses were successfully dilated. After an average follow-up of 49 months (median 51 months, range 7-93), only six patients (7%) developed late recurrence of symptoms requiring further treatment. Six patients have died and 12 have been discharged from follow-up. The cumulative success rate beyond 5 years' follow-up was 80%. Complications requiring surgical intervention occurred in four patients (5%). Double-balloon percutaneous transluminal angioplasty was seen to be an effective procedure which produced lasting improvement and is recommended as the first choice treatment for localised stenotic and occlusive disease at the aortic bifurcation. PMID- 8454076 TI - The role of pulse-generated run-off, Doppler ultrasound and conventional arteriography in the assessment of patients prior to femorocrural bypass grafting. AB - One of the most important prerequisites prior to femorocrural bypass is the identification of a patent calf vessel. To determine the ability of three preoperative investigations to demonstrate patent distal vessels we compared preoperative conventional arteriography, Doppler ultrasound measurement of ankle systolic pressure (ASP) and pulse generated run-off (PGR). PGR and ASP both identified significantly more calf vessels than did preoperative conventional arteriography. However, only PGR had the ability to distinguish those vessels suitable for bypass grafting from those unsuitable for grafting. These results demonstrate that PGR is the investigation of choice prior to femorocrural bypass. PMID- 8454077 TI - Reversal of the post-ischaemic changes in skeletal muscle blood flow and viability by a novel inhibitor of lipid peroxidation. AB - The role of a novel inhibitor of lipid peroxidation (U74500A) in modifying post ischaemic changes in skeletal muscle blood flow, viability and oedema has been investigated in a rat model of 6 h unilateral hindlimb ischaemia followed by 4 h reperfusion. During reperfusion, gastrocnemius muscle blood flow (GMBF) was measured (radiolabelled microspheres) at 10, 120 and 240 min and a perfusion index (PI) calculated between the reperfused and contralateral normal limb. Muscle viability (GMV--nitroblue tetrazolium) and oedema (wet:dry weight ratio, reperfused: contralateral limb) were assessed after 4 h reperfusion. GMBF in untreated controls, compared to normal animals, demonstrated a triphasic pattern of low reflow at 10 min [PI 0.08 (0.01-0.13) vs. 1.05 (0.68-1.18), p < 0.01], relative reperfusion at 120 min [PI 0.29 (0.09-0.59) vs. 0.97 (0.79-1.13), p < 0.05] and reperfusion injury at 240 min [PI 0.05 (0.01-0.14) vs. 1.01 (0.73 1.16), p < 0.01] with a median GMV at 240 min of 52.9% (33.3-61.4), p < 0.01 vs. normals and 6 h ischaemia alone (GMV 100% in all limbs) and an oedema index of 1.23 (1.09-1.37 p < 0.01 vs. normal. In contrast, rats receiving U74500A (2 mg/kg i.v. infusion commencing 30 min prior to revascularisation) exhibited enhanced GMBF throughout reperfusion [PI 10 min: 3.26 (2.56-3.63); 120 min: 2.03 (1.73 2.25); 240 min: 2.13 (1.75-2.44), p < 0.01 vs. controls and normals] with complete muscle salvage [GMV 100% in all reperfused muscles, p < 0.01 vs. controls, not significant (NS) vs. normals and 6 h ischaemia].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454078 TI - Cerebral blood flow during carotid endarterectomy determined by three dimensional SPECT measurement; relation to preoperative risk assessment. AB - Cross-clamping of the carotid artery during carotid endarterectomy implies a risk of developing an ischaemic insult. To evaluate the effects of carotid artery occlusion on cerebral blood flow (CBF), both hemispheric and regional CBF (rCBF) were investigated using intravenously (i.v.) administered 133Xenon with 3 min clearance recording time for two-dimensionally (hemispheric CBF) and 99m technetium-hexamethylpropylene amine oxime (99mTC-HMPAO) for three-dimensionally single photon emission computed tomography (SPECT) measurements (rCBF). Thirteen patients scheduled to undergo carotid endarterectomy anaesthetised with fentanyl/isoflurane participated in the study. Preoperative evaluation included investigation of rCBF with SPECT in all participants. Two intraoperative 133Xe CBF measurements were performed in each patient, before and after occlusion of the carotid artery. The preoperative rCBF measurement constituted the reference, for technical reasons, for the intraoperative investigations of rCBF during cross clamping, which was completed immediately after the hemispheric measurements. The increase in preoperative risk evaluation as described by Sundt et al. and modified by Cho et al. corresponded excellently to a decrease in hemispheric CBF due to cross-clamping. A significant decrease in rCBF (p < 0.005) was present between patients with high and low preoperative risk score for the region of the middle cerebral artery. In this region, a correlation between decrease in rCBF and corresponding decrease in hemispheric CBF was also present. The present study demonstrates that the vascular regions of the ipsilateral middle cerebral artery are the most vulnerable vascular area during cross-clamping in individuals with high preoperative risk score.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454079 TI - Isolated profundaplasty in critical limb ischaemia--still of any use? AB - Because of the improved quality of peripheral bypass surgery, the role of isolated profundaplasty in revascularisation of the critically ischaemic limb has become very limited. This retrospective study of 72 isolated profundaplasties performed for critical limb ischaemia revealed a clinical improvement 1 year postoperatively of 39% in the period 1978-1983 and of only 9% between 1984-1990. In the total period, patient survival after 1 year was 81% and limb salvage 60%. Clinical, haemodynamic and arteriographic parameters were analysed for their predictive value of clinical success. The presence of tissue necrosis or ulceration (clinical stage IV) affected clinical outcome negatively (p < 0.05). Risk factors and indicators for arteriosclerotic disease, age of the patient and ankle-brachial systolic pressure index (ABI) had no significant predictive value. Evaluation of the preoperative arteriographies revealed that only the aspect of the profunda femoris artery beyond its orifice was of significance: there was a strong relationship between the absence of obstructive disease in this part of the artery and clinical improvement (p < 0.005). These two significant parameters may be guidelines when considering an isolated profundaplasty as an alternative in the treatment of critical limb ischaemia. However, in the presence of other treatment possibilities nowadays, especially bypass surgery, the procedure appears to offer a very poor success rate. PMID- 8454080 TI - Predictive value of bruits and Doppler pressure measurements in detecting lower limb arterial stenosis. AB - The value of bruits and Doppler ankle pressure measurements as indicators of arterial stenosis was studied in 50 patients with symptoms of lower limb ischaemia. The iliac and femoropopliteal arteries were examined for bruits, ankle systolic pressures were measured before and after an exercise stress test and the results were compared to the findings of digital subtraction angiography (DSA). Patients with occlusive lesions in the iliac and femoropopliteal arteries were not analysed. This left a group of 37 symptomatic legs in which the popliteal pulse was palpable. In this sub-group, DSA demonstrated 25 limbs with arterial stenoses and 12 limbs without evidence of a stenosis. The presence of a bruit had a sensitivity of 80%, a specificity of 75%, a positive predictive value of 87%, a negative predictive value of 64% and an accuracy of 78%. A fall in Doppler ankle pressure of > or = 20 mmHg had a sensitivity of 92%, a specificity of 75%, a positive predictive value of 88%, a negative predictive value of 82% and an accuracy of 86%. When used selectively, clinical examination for bruits has good accuracy and may be of clinical value in the early identification of patients who are suitable for percutaneous transluminal angioplasty. PMID- 8454081 TI - When do vascular surgeons prescribe antiplatelet therapy? Current attitudes. AB - A large number of studies have addressed the efficacy of antiplatelet agents in the prevention of primary and secondary atherosclerotic events. We have undertaken to review the literature and conclude that there is good evidence for the routine prescription of antiplatelet therapy in the prevention of secondary atherosclerotic events in patients with unstable angina, myocardial infarction, transient ischaemic attacks and post-arterial reconstruction. The evidence for any benefit in the prevention of vascular graft occlusion is less clear cut. We therefore conducted a postal survey of Vascular Surgeons in Britain and Ireland, receiving 112 responses to 134 questionnaires. Forty-seven percent of surgeons used antiplatelet therapy following any vascular procedure that they undertook. The rest were more selective in their use of these drugs, reserving them for specific vascular reconstruction, e.g. with synthetic grafts. Five percent of surgeons used anti-platelet aggregating prophylaxis only in patients following transluminal balloon angioplasty. In view of extensive evidence of reduction in long-term vascular mortality and non-fatal vascular events by the use of these drugs in patients who have had a primary vascular event, we would suggest that there is a strong argument for the routine use of anti-platelet drugs in patients presenting with arterial disease to a Vascular Surgeon, regardless of vascular reconstruction, angioplasty or type of graft used. PMID- 8454082 TI - Acute thrombogenicity and 4 weeks healing properties of a new stretch-ePTFE graft. AB - Recently a new expanded polytetrafluoroethylene (ePTFE) graft with length compliant characteristics has been developed. The present study compared the acute thrombogenicity and 4 weeks healing characteristics of the stretch ePTFE graft to standard ePTFE grafts in vivo. Grafts of 6 cm length and 8 mm internal diameter were inserted end-to-side into the iliac arteries in pigs. Platelet adhesion was assessed by infusing indium-111-oxine (20 MBq) labelled autologous platelets and dynamically imaging the grafts. Explanted grafts (n = 14) were opened longitudinally and the thrombus-free surface (TFS) and segmental accumulation of platelets were determined. Stretch ePTFE grafts had significantly less platelet deposition when compared to standard ePTFE graft (p < 0.01). The dynamic increase of activity from 10 min after start of measurement was also significantly reduced (p < 0.05) for 170 min as compared to standard ePTFE grafts. TFS was 68 +/- 5% for stretch ePTFE and 37 +/- 5% for standard ePTFE grafts (p < 0.01). After explanation and fixation the grafts were investigated by light microscopy, scanning and transmission electron microscopy. At 1 week after surgery, both kind of grafts were covered by a fibrinous layer containing platelets and leukocytes. After 2 weeks a pseudoendothelial layer was found in the perianastomotic regions. After 4 weeks, two out of four standard ePTFE grafts were occluded due to intimal hyperplasia and subsequent thrombosis in the midportion of the grafts. All stretch ePTFE grafts were patent and covered by a smooth pseudointima. This study thus demonstrates a lower acute thrombogenicity in stretch ePTFE grafts compared to the standard graphs. PMID- 8454083 TI - Value of Duplex scanning in the selection of patients for percutaneous transluminal angioplasty. AB - Duplex scanning is becoming increasingly important in the diagnosis and follow-up of arterial lesions, though most surgeons and radiologists currently still prefer diagnostic angiography prior to percutaneous transluminal angioplasty (PTA). We performed PTA based on Duplex scanning alone in 31 selected patients during the last 6 months of 1991. Seventeen patients were treated for lower extremity ischemia and 14 for (a)-symptomatic stenosis in a peripheral bypass. Results of Duplex scanning were compared to the finding of PTA to assess the value of Duplex scanning done prior to PTA. Duplex scanning showed 51 lesions eligible for PTA, in 48 of 51 lesions (94%) the location as found with Duplex scanning was in agreement with the findings of the angiogram during PTA. Of a total of 31 patients scheduled for PTA, Duplex scanning predicted the indication for PTA adequately in 26 patients (84%). No complications were seen. Duplex scanning proved to be a valuable tool in the detection of lesions suitable for PTA. Furthermore, puncture site and route can be determined by means of Duplex scanning. PMID- 8454084 TI - Aortofemoral bypass in the presence of total juxtarenal aortic occlusion. AB - Forty-two patients with total juxtarenal aortic occlusion were offered aortobifemoral bypass over a 6 year period. The majority presented with claudication and males predominated. In all patients, aortobifemoral bypass was successfully performed. The groins were initially explored and the aorta was then thrombectomised prior to the standard aortobifemoral bypass. Follow-up period ranged between 6 months and 5 years. There was a 4.8% perioperative mortality. Graft occlusion occurred in two patients in the immediate postoperative period, resulting in major amputation in one patient. Three patients developed graft occlusion during the period of follow-up, none of whom required amputation. Graft sepsis occurred in one patient and one patient developed a false aneurysm. We conclude that angiography cannot predict the feasibility of bypass in the presence of total aortic occlusion, and in our hands aortobifemoral bypass is feasible in all these patients. Early results are no different from the rest of the patients with aortoiliac disease. PMID- 8454085 TI - Factors determining the outcome of crural and pedal revascularisation for critical limb ischaemia. AB - The influences of clinical factors, site of distal anastomosis, type of graft and angiographic run-off, on graft patency and limb salvage following 141 femorocrural and pedal bypasses in 121 patients were investigated retrospectively. The grafts consisted of 111 femorocrural and 30 pedal bypasses; 49% of the patients had diabetes mellitus. Venous grafts were implanted in 116 limbs, using either in situ vein (65), reversed vein (38) or composite vein (13) graft. Twenty-five prosthetic grafts (14 PTFE and 11 umbilical veins) were inserted. After 1, 2, 3 and 4 years of follow-up, the primary cumulative patency rates for all grafts were respectively 67, 61, 55 and 55%, and the secondary patency rates were 75, 70, 64 and 64%. The site of distal anastomosis had no influence on graft patency rate; neither was there any significant effect of clinical risk factors and run-off on graft patency. Prosthetic grafts showed significantly lower patencies compared to venous grafts and appeared to be the only independent prognostic risk factor for graft failure (multivariate analysis; p = 0.03). Overall limb salvage rate was 84% at 3 years. There were four amputations with patent grafts. The limb salvage rates for in situ vein, reversed/composite vein and prosthetic grafts were 89, 79 and 66% at 3 years, respectively. Various bypass grafts to the crural and pedal arteries are successful and durable. The use of prosthetic grafts results in significantly lower patency rates, but appears to be effective for limb salvage. PMID- 8454086 TI - Intra-arterial injection of temazepam in drug abusers. AB - The effects of intra-arterial injection of Temazepam are described in 11 drug abusers admitted over a 6 month period. All patients suffered severe ischaemia, and injection into the radial artery invariably resulted in tissue loss leading to amputation. The pathogenesis and options for treatment are discussed. PMID- 8454087 TI - Chest and subclavian artery trauma: avoiding thoractomy. PMID- 8454088 TI - An aid to renal preservation during repair of suprarenal abdominal aortic aneurysms. PMID- 8454089 TI - Gastrointestinal bleeding from a fistula between an aneurysm of the hepatic artery and the pancreatic duct. PMID- 8454091 TI - Health care reform what can/should we expect/do? PMID- 8454090 TI - Duodenal obstruction following reconstruction of abdominal aortic aneurysm. AB - Two patients developed duodenal obstruction, believed to be due to collagenous adhesions between the duodenum and the Dacron graft itself, following repair of an abdominal aortic aneurysm. The diagnosis was suspected because of a continuous copious bile stained nasogastric aspirate and was confirmed by upper gastrointestinal barium studies. Conservative management for several days with nasogastric aspiration and intravenous hyperalimentation led to resolution of the obstruction. We believe this complication is probably under-reported but will generally resolve with conservative measures. PMID- 8454092 TI - Anaphylaxis to protamine masquerading as an insulin allergy. AB - This is the case of a 62-year-old man referred for the evaluation of insulin allergy. This patient had reacted to the subcutaneous injection of Novolin 70/30 (Squibb, Princeton, N.J.) and Humulin NPH (Eli Lilly, Indianapolis, Ind.). These reactions were characterized by the immediate onset of diffuse pruritic urticaria and angioedema with progression to hypotension as well as a local reaction. Past history also included anaphylactic shock after intravenous administration of protamine sulfate used for heparin reversal during arterial bypass surgery. Immediate hypersensitivty skin testing to protamine containing (NPH) insulin and protamine sulfate USP were strongly positive, while Lente insulin (Eli Lilly, Indianapolis, Ind.) and controls were negative. RAST tests revealed the titers > 24 ng/ml of protamine specific IgE with 98 percent inhibition and 1163 ng/ml of protamine specific IgG with 29 percent inhibition, while levels of insulin specific antibodies were negligible. Subsequently, the patient was treated with non-protamine containing insulin preparation, Lente insulin, without further incident. This study confirms the diagnosis of Type I hypersensitivity to protamine sulfate masquerading as insulin allergy. PMID- 8454093 TI - Noncardiogenic pulmonary edema: a certain etiology? AB - An emergency paramedic call finds a 40-year-old woman unresponsive on the floor with shallow respiration, pink froth and vomitus about the mouth, pulse 36, blood pressure 136 by palpation. She had been cleaning in her kitchen and common household chemicals were open nearby. On arrival in the Emergency Department, a chest X-ray showed bilateral pulmonary infiltrates consistent with pulmonary edema. Heart size normal. Despite all efforts, the woman died. Post mortem examination revealed ruptured cerebral vascular malformation as the cause of death. PMID- 8454094 TI - The National Practitioner Data Bank in operation. PMID- 8454095 TI - Fees and health care costs. PMID- 8454096 TI - Noninvasive ventilatory support. PMID- 8454097 TI - Informed consent for transfusion. PMID- 8454098 TI - Insurance, access and managed care. PMID- 8454099 TI - Primary access--another angle. PMID- 8454100 TI - Nonenzymatic glycosylation of laminin and the laminin peptide CIKVAVS inhibits neurite outgrowth. AB - Nerve regeneration in diabetic animals is delayed and qualitatively impaired, but the mechanisms responsible for these defects have not been elucidated. The extracellular matrix protein laminin promotes the extension of neuronal processes, and recent studies have localized neurite-promoting activity to a lysine-containing sequence (IKVAV) within the laminin molecule. Because long lived molecules such as laminin are likely to accumulate excessive amounts of nonenzymatic glycosylation products in diabetic subjects, we have investigated whether such adduct formation on laminin or the IKVAV peptide affects their neurite-promoting properties. These studies used the murine neuroblastoma cell line NB2a, which extends neurites on laminin when differentiated by cAMP. Neurite outgrowth in NB2a cells plated on glycosylated laminin was significantly decreased from that occurring on unmodified laminin. Similarly, neurite outgrowth in NB2a cells plated on glycosylated IKVAV peptide was inhibited compared with that observed on native IKVAV. These data suggest that nonenzymatic glycosylation of a biologically active domain within laminin may contribute to impaired nerve regeneration in diabetes. PMID- 8454101 TI - Linkage of chromosomal markers on 4q with a putative gene determining maximal insulin action in Pima Indians. AB - Insulin action in vivo varies widely in nondiabetic Pima Indians. Not all of this variance is attributable to individual differences in obesity, physical fitness, sex, or age, and after correcting for these co-variates, measures of insulin action aggregate in families. Insulin action at maximally stimulating insulin concentrations has a trimodal frequency distribution, particularly among obese individuals. This is consistent with the hypothesis that a codominantly inherited autosomal gene, unrelated to obesity, determines MaxM in the population. Preliminary sib-pair linkage analyses indicated the possibility of linkage between MaxM and the GYPA/B locus (encoding the MNSs red cell surface antigens) on chromosome 4q. To confirm and extend these findings, 10 additional loci on 4q were typed in 123 siblings and many of their parents from 46 nuclear families. The results indicate significant (P < 0.001) linkage of the FABP2 and ANX5 loci on 4q with MaxM, and of FABP2 with fasting insulin concentration. No linkage was found between the 4q markers and obesity. Our findings indicate that a gene on 4q, near the FABP2 and ANX5 loci, contributes to in vivo insulin action in Pima Indians. PMID- 8454102 TI - In vivo glucose utilization by individual tissues in virgin and pregnant offspring of severely diabetic rats. AB - Adult offspring of diabetic rats or SDF rats are characterized by insulin resistance in the liver and extrahepatic tissues; this insulin resistance does not worsen during pregnancy. In this study, we determined the glucose metabolic index in tissues of anesthetized virgin and pregnant control and SDF rats in basal conditions and during a euglycemic hyperinsulinemic clamp. Tissues comprised insulin-sensitive tissues (five skeletal muscles, diaphragm, and periovarian white adipose tissue) and control tissues (duodenum and cerebrum). In addition, this study measured the GMI of placenta and fetuses. In basal conditions, SDF rats showed a slight decrease (9-29%) in the GMI of skeletal muscles compared with control rats; it was not altered by pregnancy in any of the tissues. During physiological hyperinsulinemia, virgin SDF rats exhibited a 25 70% decrease in the GMI of skeletal muscles compared with control rats; this decrease was not observed in diaphragm, or in adipose tissue in which the GMI was found to be increased. During pregnancy, SDF rats did not show an additional drop in the GMI of skeletal muscles, whereas the GMI of both skeletal muscles and adipose tissue was clearly diminished (25-60%) in control rats. The GMI of skeletal muscles was therefore comparable in pregnant control rats and SDF rats. The placental, but not fetal, GMI was increased by 24% during hyperinsulinemia in control rats; the placental and fetal GMIs, in basal and hyperinsulinemic conditions, were similar in control rats and SDF rats. In conclusion, skeletal muscles, but not white adipose tissue, are involved in the peripheral insulin resistance of the SDF rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454103 TI - Race-dependent health risks of upper body obesity. AB - For Caucasian women, an excess of abdominal fat is a potent risk factor for the development of diabetes and cardiovascular disease. However, there is limited information regarding the health risks of upper body obesity for African-American women despite a higher prevalence of obesity and obesity-related diseases and a reportedly higher prevalence of abdominal fat accumulation. This study aimed to determine whether UBO, independent of total body fatness, is as potent a diabetic and CVD risk factor for black women as has been confirmed for white women. Diabetes and CVD risks and androgenic status were assessed in nondiabetic, premenopausal women of similar body fatness who differed by race (black or white) and body fat distribution (UBO or lower body obesity). In black women, high density lipoprotein cholesterol was the only measurement adversely affected by abdominal fat; HDL cholesterol was significantly lower in the black UBO group (1.14 +/- 0.05 mM) compared with the black LBO group (1.37 +/- 0.08 mM). This contrasts markedly with our findings in white women. In confirmation of previous reports, white UBO women, compared with white LBO counterparts, had significantly higher glucose (967.6 vs. 709.2 mM/2 h) and insulin (120.5 vs. 52.1 pM/2 h) areas and significantly lower peripheral insulin sensitivities (0.99 vs. 2.95 x 10(-4) min-1/microU/ml). In addition, HDL cholesterol levels were significantly lower in the white UBO group (1.03 mM) compared with the white LBO group (1.49 mM), whereas plasma TG levels (white UBO, 1.72 vs. white LBO, 0.88 mM) and dBPs (white UBO, 84 vs. white LBO, 75 mmHg) were significantly higher.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454104 TI - No effect of deferoxamine therapy on glucose homeostasis and insulin secretion in individuals with NIDDM and elevated serum ferritin. AB - Deferoxamine has been proposed as a potentially important therapy for individuals with NIDDM and mild elevations in serum ferritin. Previously, iron chelation therapy with intravenous deferoxamine over a 5-13-wk period has been reported to normalize serum ferritin and markedly improve glycemic control. To confirm these results and to study potential beneficial effects of deferoxamine on insulin secretion, 9 individuals with NIDDM and elevated serum ferritin levels were treated twice weekly with deferoxamine infusion, following a previously described protocol. Although 8 of 9 subjects achieved normal or near-normal serum ferritin values after deferoxamine therapy, we found little evidence that it produced beneficial effects on glycemic control. Fasting glucose levels pre- and post deferoxamine therapy were unchanged (11.6 +/- 1.2 and 11.3 +/- 1.5 mM, respectively, P = 0.80). GHb levels declined slightly after deferoxamine therapy (9.3 +/- 0.7 vs. 8.8 +/- 0.7%, P < 0.05); however, this effect was small and was not associated with elimination of or even substantial reduction in insulin or oral hypoglycemic therapy. Deferoxamine therapy did not significantly alter fasting insulin or C-peptide levels, nor stimulated insulin or C-peptide responses to intravenous arginine or glucose. During follow-up studies 1.5-8 mo after deferoxamine therapy, serum ferritin levels again were elevated in 5 of 8 subjects who showed an initial response. Thus, although deferoxamine therapy reduced serum ferritin levels in our subjects, we were unable to confirm a previous report that this effect was associated with any meaningful improvement in glycemic control or insulin secretion. PMID- 8454105 TI - Loss of potentiating effect of hypoglycemia on the glucagon response to hyperaminoacidemia in IDDM. AB - IDDM subjects lose the ability to release glucagon during hypoglycemia. Because replacement of basal levels of amino acids enhances the glucagon response to hypoglycemia in healthy subjects, we tested whether raising amino acid levels during hypoglycemia could reverse the defective alpha-cell response in IDDM patients. For this purpose, 11 IDDM patients (HbA1 9.4 +/- 0.6%) and 8 healthy, nondiabetic subjects received two hypoglycemic insulin clamp studies (0.8 mU.kg-1 x min-1) in which plasma glucose was clamped at 55 mg/dl (3.08 mM) for 180 min. During one of the studies, an infusion of amino acids was superimposed between 120 and 180 min (0.3 g.kg-1 x h-1). This dose of amino acids had a small effect on plasma glucagon levels during euglycemic hyperinsulinemia that was comparable in normal and IDDM subjects. In healthy control subjects, plasma glucagon rose by 80% during the initial hypoglycemic phase of the study. The addition of amino acids produced a further sharp (200-250 ng/L, P < 0.02) rise in plasma glucagon, such a change did not occur in the absence of amino acids. In contrast, plasma glucagon in IDDM patients failed to increase during hypoglycemia alone and rose by only 40-50 ng/L (P < 0.05 vs. controls) when amino acid infusion was superimposed, even though plasma amino acid levels rose to the same extent in IDDM and control subjects. More importantly, the rise in glucagon produced by amino acids was comparable during hypoglycemic and euglycemic hyperinsulinemia in the IDDM patients, results strikingly different from those observed in nondiabetic control subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454106 TI - High risk of progression to NIDDM in South-African Indians with impaired glucose tolerance. AB - A four-yr prospective study was undertaken to examine the natural history of IGT in 128 South-African Indians classified as such at year 0 of the study, based on WHO criteria. Subjects were reexamined at year 1 and year 4. Of the 113 subjects who completed the study, 50.4% progressed to NIDDM (rate of progression 12.6%/yr), 24.8% persisted with IGT, and 24.8%, reverted to NGT. The majority (72%) who progressed to NIDDM did so in year 1. At year 1, 47 subjects were still classified as IGT; of the 40 subjects completing the study, 16 subjects (40%) progressed to NIDDM, 17 subjects (42.5%) persisted with IGT, and 7 subjects (17.5%) reverted to NGT. Examination of risk factors predictive of subsequent progression to NIDDM was undertaken by analysis of baseline variables in two ways: When year 0 was used as baseline (in 113 IGT0 subjects), significant predictive risk factors were the FPG and 2-h plasma glucose concentrations. All subjects who at year 0 had 2-h plasma glucose > or = 10.2 and < 11.1 mM or FPG > or = 7.3 but < 7.8 mM, subsequently progressed to NIDDM. When year 1 was used as baseline (40 IGT1 subjects), 90-min plasma glucose concentration (midtest level) was found to be a significant risk factor for development of NIDDM. In conclusion, this study has demonstrated that in South-African Indians with IGT, the majority (50.4%) progress to NIDDM within 4 yr; significant predictors of subsequent diabetes are the baseline fasting and 2-h plasma glucose concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454107 TI - Benfluorex normalizes hyperglycemia and reverses hepatic insulin resistance in STZ-induced diabetic rats. AB - We have examined the effect of chronic (20 days) oral administration of benfluorex (35 mg/kg) in a rat model of NIDDM, induced by injection of STZ 5 days after birth and characterized by frank hyperglycemia, hypoinsulinemia, and hepatic and peripheral insulin resistance. We assessed the following: 1) basal blood glucose and insulin levels, 2) glucose tolerance and glucose-induced insulin release in vivo and in vitro, and 3) basal and insulin-stimulated in vivo glucose production and glucose utilization, using the insulin-clamp technique in conjunction with isotopic measurement of glucose turnover. The in vivo insulin response of several individual tissues also was evaluated under the steady-state conditions of the clamp, using the uptake of the glucose analogue 2-deoxy-D glucose as a relative index of glucose metabolism. In the benfluorex-treated diabetic rats, postabsorptive basal plasma glucose levels were decreased (8.1 +/- 0.2 mM compared with 10.5 +/- 0.5 mM in the pair-fed untreated diabetic rats and 6.1 +/- 0.2 mM in the benfluorex-treated nondiabetic rats), whereas the basal and glucose-stimulated intravenous glucose tolerance test plasma insulin levels were not improved. Such a lack of improvement in the glucose-induced insulin release after benfluorex treatment was confirmed under in vitro conditions (perfused pancreas). In the pair-fed untreated diabetic rats, the basal glucose production and overall glucose utilization were significantly increased, and during hyperinsulinemia both liver and peripheral tissues revealed insulin resistance. In the benfluorex-treated diabetic rats, the basal glucose production and basal overall glucose utilization were normalized. After hyperinsulinemia, glucose production was normally suppressed, whereas overall glucose utilization was not significantly improved.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454108 TI - IDDM in rats induced by thymectomy and irradiation. AB - A diabetic syndrome closely resembling human IDDM has been induced in rats of specific pathogen-free origin by a combination of thymectomy and irradiation, with an overall incidence (10 wk postirradiation) in female rats of 34% for acute disease and 47% for islet lesions. Males were slightly more susceptible than females. Clinical features of the syndrome included hyperglycemia, insulinopenia, ketosis, and lipidemia, and corresponding islet pathology ranged from diffuse atrophy to focal atrophy and insulitis. Onset was usually acute, and the disease fatal unless early insulin therapy was initiated. Lymphocytic thyroiditis also was observed in a proportion of thymectomized and irradiated rats (49% in females) over the same period but with no apparent correlation to the occurrence of diabetes. A significant decrease in the incidence of disease was found in thymectomized and irradiated rats of conventional origin when compared with genetically identical specific pathogen-free rats, implicating a role for environmental factors in disease susceptibility. Diabetes inducement also was found to be strain related but not RT1u dependent. Both clinical signs and islet lesions were inhibited by early reconstitution of thymectomized and irradiated animals with syngeneic lymphoid cells from normal donors. Islet lesions and glucose intolerance could be transferred to syngeneic recipients by concanavalin A-activated lymphoid cells from acute diabetic donors. The close similarities between this experimental syndrome induced by immunological manipulation and the clinical condition in humans provide further evidence for an immune-mediated pathogenesis for IDDM. PMID- 8454109 TI - Glucokinase gene variants in the common form of NIDDM. AB - To determine whether a structural defect in glucokinase could be a primary cause of glucose intolerance in the common form of NIDDM, the prevalence of mutations in the gene in 60 American black NIDDM patients was investigated. First, by Southern blot analysis of DNA from a subset of randomly selected subjects (n = 20), no gross deletions, insertions, or rearrangements of the gene were detected. Next, the 5'-untranslated and coding regions of the gene were amplified directly from genomic DNA by the polymerase chain reaction. PCR products were screened for mutations by using single-strand conformational polymorphism analysis. A total of nine variants were identified, with two in the 5'-UT regions of islet exon 1, two in the 5'-UT region of liver exon 1, and five in the coding regions. For islet exon 1, 5 of 60 NIDDM patients had both variants in the 5'-UT region; and for liver exon 1, two variants each occurred in 1 of 60 NIDDM patients. The coding region variants included a missense mutation in islet exon 1, substitution of Ala11 (GCC) with Thr11 (ACC), found in 2 patients. The biological consequences of this mutation and the mutations in the 5'-UT portion of the gene have yet to be determined. The rest of the variants were third base pair changes of codons, i.e., silent. A common polymorphism, which was in linkage equilibrium with microsatellite repeats GCK1 and GCK2, was found in intron 9, and a variant in intron 2 in both alleles of 1 patient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454110 TI - Correction of erythrocyte deformability defect in ALX-induced diabetic rabbits after treatment with aminoguanidine. AB - To test whether treatment with aminoguanidine, a drug known to prevent cross linking between glycated proteins, is effective in improving reduced erythrocyte deformability in diabetes, we studied a group (n = 6) of ALX-induced long-term (12.7 +/- 2.2 mo of hyperglycemia) diabetic New Zealand white rabbits before and after 20 wk of treatment with aminoguanidine (100 mg.kg-1 x day-1). The key findings were as follows: 1) at 12 wk of treatment with aminoguanidine, mean erythrocyte deformability normalized and remained within the normal reference range throughout the period of aminoguanidine administration; 2) 10 wk after discontinuing aminoguanidine in a subset of diabetic rabbits, mean erythrocyte deformability deteriorated by approximately 50%; 3) blood glucose and total GHb did not vary significantly during treatment with aminoguanidine nor after its discontinuation. PMID- 8454111 TI - Oxidative deamination of methylamine by semicarbazide-sensitive amine oxidase leads to cytotoxic damage in endothelial cells. Possible consequences for diabetes. AB - Methylamine was observed to be deaminated by several semicarbazide-sensitive amine oxidases, which were prepared from blood and vascular tissues of various species, including humans. Although methylamine itself is relatively nontoxic toward endothelial cells obtained from both human umbilical vein and calf pulmonary artery, it becomes very toxic in the presence of SSAO. SSAO inhibitors (i.e., MDL-72974A) effectively protected the cells from methylamine-SSAO-induced damage. The cytotoxicity seems, therefore, to be a consequence of the deamination of methylamine. Our findings suggest that formaldehyde, the deaminated product of methylamine, may be responsible for these toxic effects. Human serum, which also contains SSAO, was also capable of deaminating methylamine and causing cytotoxicity to cultured endothelial cells. Both methylamine and SSAO circulate in human blood, and their concentrations in the blood of normal healthy subjects are quite close to those required to induce cytotoxicity in tissue-cultured cells. Both SSAO activity and methylamine levels have been reported to be increased in the blood of diabetic individuals. Blood SSAO activity also has been reported to be elevated in the blood of STZ-induced diabetic rats. It is possible, therefore, that an abnormal metabolism of methylamine may be involved in endothelial injury, and that it may subsequently induce atherosclerotic plaque formation and thus be involved in the cardiovascular disorders seen in diabetes. PMID- 8454113 TI - Chemical cross-linking detects association of insulin receptors with four different class I human leukocyte antigen molecules on cell surfaces. AB - Class I major histocompatibility complex molecules have been shown to be physically associated with insulin receptor molecules on the surfaces of a number of different cell types. The class I human leukocyte antigen (human MHC) phenotype of B lymphoblasts correlates with the affinity of IR for insulin. This correlation could be the result of association of some but not other HLA molecules with IR, or could reflect differences in the way in which association with an HLA molecule affects the function of IR. To distinguish between these possibilities, this study isolated complexes of four different class I HLA molecules with IR. Expression of some of these molecules correlates with high affinity IR, whereas expression of others correlates with 5- to 10-fold lower affinity IR. This study found that chemical cross-linking was necessary to stabilize HLA-IR complexes, and all four of the class I HLA molecules studied, HLA-A1, HLA-A2, HLA-B5, and HLA-B8, can form complexes with IR. PMID- 8454112 TI - The effects of perindopril and triple therapy in a normotensive model of diabetic nephropathy. AB - The effect of the angiotensin-converting enzyme inhibitor, perindopril, on functional and structural parameters of diabetic nephropathy has been compared with triple therapy (hydralazine, reserpine, and hydrochlorothiazide) in normotensive, STZ-induced diabetic Sprague-Dawley rats. Animal groups included control rats, diabetic rats treated with perindopril, diabetic rats receiving triple therapy, and untreated diabetic rats. Treatment was continued for 32 wk. Blood pressure reduction and severity of diabetes, as assessed by body weight and glycemic control were similar with both drug regimens. A similar rise in plasma renin activity occurred in the two groups receiving antihypertensive drugs, whereas the perindopril but not the triple therapy group had suppressed plasma angiotensin-converting enzyme activity. No significant difference was observed in renal function among the four groups. Diabetes was associated with a progressive increase in albuminuria, but this rise was ameliorated by both perindopril and triple therapy. No significant difference was noted in albuminuria between triple therapy and perindopril-treated diabetic rats. Diabetes was associated with glomerular basement membrane thickening, mesangial expansion, and glomerular volume. No glomerular ultrastructural parameter was affected by antihypertensive drugs. No specific benefit of angiotensin-converting enzyme inhibition over triple therapy could be detected in this normotensive model of diabetic nephropathy. PMID- 8454114 TI - Transcription factor jun-B is target of autoreactive T-cells in IDDM. AB - Target antigens defined by autoantibodies in IDDM include insulin, a putative glycolipid that reacts with islet cell antibodies, and a 64,000-M(r) protein recently identified as glutamic acid decarboxylase. In addition, some IDDM sera that contain antibodies to glutamic acid decarboxylase also coprecipitate a 38,000-M(r) protein from islets. This study used a high titer anti-38,000-M(r) serum to screen bacteriophage lambda cDNA expression libraries and identified human islet and placental clones encoding jun-B, the nuclear transcription protein, of predicted 38,000 M(r). Peripheral blood T-cells exhibited significant proliferation in response to a recombinant fragment of jun-B (amino acids 1-180) in 12 of 17 (71%) recent-onset IDDM subjects, 8 of 16 (50%) ICA-positive first degree relatives of IDDM subjects who were at risk, 3 of 12 (25%) other autoimmune disease subjects, and 0 of 10 healthy control subjects. Proliferation to tetanus toxoid did not differ significantly between the groups. Responses to jun-B were not related to age, sex, or human leukocyte antigen status. Thus, autoreactive T-cells identify a novel antigen, p38 jun-B, in IDDM and appear to indicate subjects at risk for the development of clinical disease. PMID- 8454115 TI - Autoantibodies in IDDM primarily recognize the 65,000-M(r) rather than the 67,000 M(r) isoform of glutamic acid decarboxylase. AB - Glutamic acid decarboxylase autoantibodies may aid in rapid screening strategies predicting IDDM before clinical onset. Rat islets contain GAD65 and GAD67 autoantibody targets, but human islets express only GAD65, now confirmed by direct immunoprecipitation from radiolabeled rat and human islets. Because human IDDM involves beta-cell-specific autoimmunity, we tested 190 new IDDM patients and 51 healthy control subjects for antibodies to recombinant human islet GAD65, rat islet GAD67, or human insulinoma/cerebellum GAD67, each expressed separately in hamster fibroblasts. By using immunoprecipitation, sodium dodecyl sulfate polyacrylamide gel electrophoresis, and densitometric fluorogram scanning, 132 of 190 (70%) of new IDDM patients had GAD65 autoantibodies, whereas only 17 of 190 (9%) had antibodies to rat GAD67 (P < 0.001). Of healthy control subjects, 2 of 51 (3.9%) and 1 of 51 (1.9%) had antibodies to GAD65 and GAD67, respectively. All 17 GAD67 antibody-positive patients also had GAD65 antibodies; 14 of 17 with greater GAD65 than GAD67 index. Control studies showed comparable reactivity between recombinant rat and human GAD67 and between different subcellular preparations of recombinant GAD67 of either species. In conclusion, only GAD65 is expressed in human islets, the autoantibody response is primarily to this isoform, and GAD67 antibodies add little to IDDM detection. PMID- 8454116 TI - Enhancing family medicine's contribution to undergraduate medical schools. PMID- 8454117 TI - Family Medicine after one year. PMID- 8454118 TI - The influence of physician practice behaviors on patient satisfaction. AB - BACKGROUND: Previous research on the relationship between physician behavior and patient satisfaction has not always used standardized terminology and instruments to measure physician behavior. The Davis Observation Code (DOC) provides a reliable and valid means of analyzing clinically relevant units of physician behavior. The units of behavior can then be related to patient satisfaction. METHODS: One hundred new patients randomly assigned to receive care from primary care residents at a university medical center outpatient facility were evaluated. Before seeing their physicians, patients completed a previsit questionnaire to determine their general level of satisfaction with health care. During the visit, the encounter was videotaped and physician behavior characterized using DOC. After the appointment, patients completed a visit-specific satisfaction questionnaire. Multiple regression analysis was used to model the visit-specific satisfaction variables in terms of DOC measurements. RESULTS: Total visit specific satisfaction was positively related to previsit satisfaction (P < or = .05) and to time spent on health education (P < or = .001), physical examination (P < or = .05), and discussion of treatment effects (P < or = .01). There was a negative relationship with time spent on history taking (P < or = .01). Slightly more than 25% of the variability in satisfaction was explained by these five variables (R2 = .26). The general, humaneness, and quality/competence subscales of visit-specific satisfaction were also positively related to health education, physical examination, and treatment effects and negatively related to history taking. CONCLUSIONS: Patients are most satisfied with medical visits in which they talk about their specific therapeutic interventions, are examined, and receive health education. Extended general discussion of medical history is negatively related to satisfaction. PMID- 8454119 TI - Validity of the Family APGAR in patients with irritable bowel syndrome. AB - BACKGROUND: This study explores the validity of the Family APGAR (adaptability, partnership, growth, affection, and resolve), a test of family function, in persons with irritable bowel syndrome (IBS). Previous studies have reported increased stress in persons with IBS in the form of marital and interpersonal relationships. METHODS: The Family APGAR and the MMPI were completed by 198 persons, including 58 who sought care for IBS, 67 with IBS who did not seek care, and 73 who did not have the disorder. Family APGAR scores were compared for the three groups using analysis of variance. Multiple regression analysis was used to compare Family APGAR scores with both IBS group status and MMPI K and L scales. An odds ratio was calculated for the two groups with IBS. RESULTS: Mean Family APGAR scores were in the normal range for all three groups and differed by less than 1 point among the groups. The Family APGAR score did not differentiate among persons with IBS but was strongly related to the MMPI K score, a measure of defensiveness in test taking. CONCLUSIONS: The failure of the Family APGAR to detect the family dysfunction found by psychological interviewing and the strong relationship with the MMPI K scale lead us to question the construct validity of the APGAR. More sophisticated test construction is necessary to measure family dysfunction in patients who may tend to respond defensively. PMID- 8454120 TI - Levels of family involvement by resident and attending physicians. AB - BACKGROUND: Family-oriented medical care is one of the basic tenets of family practice. However, little is known about the extent to which: 1) resident physicians discuss family issues during outpatient office visits and 2) attending physicians address family issues during teaching consultations. METHODS: Two hundred and fifty-one videotaped resident-patient interviews were classified according to Doherty and Baird's Levels of Family Involvement. A similar method was used to analyze the level to which family issues were included by attending physicians during 76 individual teaching consultations with residents. RESULTS: Residents asked about family issues with individual patients or spoke directly to family members about medical concerns in 41% of interviews. Planned family conferences or emotional support of family members seldom occurred. Attending physicians inquired about family information in 6% of the one-on-one teaching consultations with residents. CONCLUSIONS: The results suggest the need for increased faculty development efforts in the area of family involvement. Further applications of the Levels of Family Involvement are needed to establish norms of family orientation for residents and community family physicians. PMID- 8454121 TI - Medical students' attitudes toward pharmaceutical marketing: possibilities for change. AB - BACKGROUND: Concerns have been expressed about physicians' acceptance of gifts from pharmaceutical companies, but few studies have examined or attempted to change medical students' attitudes about accepting such gifts. METHODS: We used a questionnaire survey to measure attitudes about accepting such gifts. We then carried out a field experiment to compare changes in second-year medical students' attitudes, seven weeks after a one-hour lecture and discussion about the appropriateness of pharmaceutical gifts, to changes in first-year students who were not exposed to the program. RESULTS: Following the intervention, second year students became less accepting of these marketing practices; first-year students showed no significant change. The difference between the groups after the intervention was statistically significant (P < .0001). CONCLUSIONS: If medical students' attitudes about accepting gifts from pharmaceutical companies need to be changed, this study suggests that the process may be fostered with little investment of curricular time. PMID- 8454122 TI - A required fourth-year ambulatory clerkship: a 10-year experience with family practice and primary care internal medicine sites. AB - Authors of recent articles have suggested increasing medical student experiences in ambulatory primary care settings to enhance general medical education and increase student interest in family practice. The University of California, San Francisco, a large, tertiary-care medical school, has operated a required ambulatory primary care clerkship for fourth-year medical students for 10 years. The clerkship uses both family practice and general internal medicine clinic sites and, since 1980, has been coordinated by the UCSF Department of Family and Community Medicine. Students have consistently rated the clerkship positively. The clerkship appears to have helped maintain the level of graduating students entering primary care residencies. Our report describes clerkship activities at both family practice and primary care internal medicine residency sites. We examine student evaluations of the experience, the potential effects of the clerkship on residency and career choices, and the advisability of implementing a joint departmental clerkship. PMID- 8454123 TI - Consumer assessment of interview skills in a family practice certification examination. AB - BACKGROUND: In New Zealand, the family practice certification examination includes an assessment that uses simulated patients. In 1990, for the first time, consumers participated in evaluating the performance of examinees in the simulated-patient section of the examination. METHODS: The consumer examiners and medically trained examiners observed the candidates during interactions with simulated patients. The consumers, medical examiners, and simulated patients independently scored the candidates' performances. One hundred and nine examination candidates participated in two simulations each, and the scoring behavior of each rater was compared. RESULTS: Consumer and medical examiners showed significant differences in their scoring behaviors, disagreeing on whether the candidate should pass or fail in 7.8% of interviews. In comparing the scores given by consumers, medical examiners, and the simulated patients, low inter observer correlations were noted. CONCLUSION: Medical personnel, consumer observers, and simulated patients all provide a different perspective on the communication skills of physicians. PMID- 8454124 TI - A successful research assistantship program as reflected by publications and presentations. AB - BACKGROUND: Many family practice programs operate student research assistantship programs, but little information is available about the outcomes of these programs. Our summer assistantship program has trained 60 students, all of whom received training in the basic steps of the research process and were required to develop and execute a research project. METHODS: To objectively measure the outcomes of our program, we recorded the number of publications and national presentations achieved by students enrolled in our family practice summer research assistantship program. RESULTS: Nine students have published articles in refereed scientific journals. Nine students have presented research findings at national meetings. Three students have won prestigious student research awards. CONCLUSIONS: Our results suggest students in a research assistantship program can learn basic research skills and execute effective research projects. PMID- 8454125 TI - Voices from family medicine: toward the 21st century. Interview by William B. Ventres and John J. Frey. AB - Throughout STFM's 25th anniversary year, we illustrated the dynamic history of family medicine using the personal narratives of some of the discipline's founders and early leaders. We have attempted to take the energy of their spoken words and put it on paper for clinician educators to learn from and lead by. For us, as authors, this process has been enriching and has caused us to reexamine and confirm the meanings of our roles as teachers in family medicine. In this final installment, we present five new voices: individuals from succeeding generations of academic family physicians. Like the many others we interviewed but have not included here, these five individuals were identified by colleagues for their demonstrated leadership in the discipline. They and others will help mold the future of family medicine well into the 21st century. PMID- 8454126 TI - Considering life-style. PMID- 8454127 TI - Pancreas divisum: results of minor papilla sphincterotomy. AB - A subpopulation of pancreas divisum patients may have pancreatic pain or pancreatitis as a result of a stenotic minor papilla. This study was undertaken to evaluate the efficacy of minor papilla sphincterotomy in 52 pancreas divisum patients who had disabling chronic pancreatic pain (n = 24), acute recurrent pancreatitis (n = 17), or chronic pancreatitis (n = 11). Patients were symptomatic for a mean time of 5.1 years and had failed to respond to conservative therapy. Minor papilla sphincterotomy was performed with a needle knife over a previously placed minor papilla/dorsal pancreatic duct stent. Clinical improvement was assessed by comparison of symptoms (using a 0 to 10 scale) and number of hospital days per month required for pain or pancreatitis for an equal period of time before and after therapy. The average duration of follow-up was 1.7 years. As compared with the chronic pain and chronic pancreatitis groups, the acute recurrent pancreatitis group had a significant reduction in the mean symptom score and number of hospital days per month. Patients with acute recurrent pancreatitis benefited from minor papilla sphincterotomy more frequently than those with chronic pancreatitis (76.5% versus 27.3%, p = 0.01) or chronic pain (76.5% versus 26.1%, p = 0.002). Complications followed 15% of the procedures; they consisted primarily of mild pancreatitis, although one additional patient died of a pancreatic abscess after a failed cannulation. Fifty percent of patients evaluated at the time of stent removal had stent-induced dorsal duct changes. The results of this study support the performance of minor papilla therapy in pancreas divisum patients who have acute recurrent pancreatitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454128 TI - Control of the volume of gastrointestinal endoscopy. PMID- 8454129 TI - Postoperative jejunogastric intussusception. PMID- 8454130 TI - Cecal volvulus after colonoscopy. PMID- 8454131 TI - Endoscopic evaluation of paraquat-induced upper gastrointestinal injury. PMID- 8454132 TI - Gastric mucormycosis in a patient with acquired immunodeficiency syndrome. PMID- 8454133 TI - Removal of an impacted esophageal endoprosthesis using a through-the-scope balloon. PMID- 8454134 TI - Endoscopic removal of a retained T tube. PMID- 8454135 TI - PEG placement in a patient with a patulous pylorus. PMID- 8454136 TI - Localized flare reaction to intravenous drug administration for conscious sedation during endoscopy. PMID- 8454137 TI - Esophageal and duodenal bezoars from Perdiem. PMID- 8454138 TI - Harpoon extraction of a common bile duct stone impacted at the ampulla of Vater with needle-knife sphincterotome. PMID- 8454139 TI - Endoscopic injection for the arrest of peptic ulcer hemorrhage: final results of a prospective, randomized comparative trial. AB - A prospective, randomized comparative study was performed to compare the hemostatic effect of endoscopic injection with normal saline, 3% NaCl solution, 50% glucose/water solution, and pure alcohol during a period of 2 years. Only patients with peptic ulcers and active bleeding or nonbleeding visible vessels were considered. Each group comprised 50 patients. The four groups were matched at random for age, sex, location of bleeders, stigmata of recent hemorrhage, shock, hemoglobin, and concomitant illness. No statistically significant difference was observed among patients injected with normal saline, 3% NaCl solution, 50% glucose/water solution, or pure alcohol in achieving initial hemostasis (82%, 90%, 86%, and 92%, respectively); rebleeding rates (7.3%, 24.4%, 14%, and 10.9%, respectively); ultimate hemostasis (78%, 68%, 78%, and 84%, respectively); number of emergency operations (5, 7, 4, and 3, respectively); and average number of days in the hospital (6.7, 6.1, 6.1, and 5.8, respectively). A tendency toward a lower blood transfusion requirement was observed in the pure alcohol group, but this tendency failed to achieve statistical significance. One patient had a perforated ulcer develop 5 days after injection of 3 ml 50% glucose/water. Otherwise, no major complication was observed. We suggest that endoscopic injection with any of the above solutions can be used as the first line modality for the arrest of peptic ulcer hemorrhage. PMID- 8454140 TI - Systemic absorption of epinephrine after endoscopic submucosal injection in patients with bleeding peptic ulcers. AB - Epinephrine injection is an effective, simple, and economical method of endoscopic hemostasis for bleeding peptic ulcers. We measured catecholamine levels in 18 patients with actively bleeding ulcers (8 gastric ulcers and 10 duodenal ulcers) treated by endoscopic injection. Injection of epinephrine (1:10,000 IU) was given until bleeding from the ulcers stopped. Catecholamine levels were assayed by high-pressure liquid chromatography. Immediately after the injection the plasma level of epinephrine rose by four to five times above the basal level and returned to the baseline in 20 minutes. Norepinephrine levels were not significantly raised in these patients. No cardiovascular complications were seen. Although adverse cardiac events have not been recorded, it seems prudent to monitor these patients closely during and immediately after epinephrine injection. PMID- 8454141 TI - Preliminary evaluation of the prototype stereoscopic endoscope: precise three dimensional measurement system. AB - A prototype stereoscopic endoscope (incorporating two charged-coupled devices), developed for the accurate three-dimensional measurement of gastrointestinal tract lesions, was initially evaluated with two-dimensional target grids and in vitro measurement of 15 objects of known size (marbles, cubes, and rectangular prisms) placed in a plastic model of the sigmoid colon. Images of the objects were captured and stored in a computer. Stereoscopic measurements were compared with results from the standard (open biopsy forceps) method by a blinded endoscopist. The volume measured with the stereoscope did not differ significantly from the true volume, whereas the volume obtained with the open biopsy forceps method differed significantly from the actual volume, consistently underestimating the actual size. The aberration ratios (percentage deviation between the measured and true volume, expressed as mean +/- SD) obtained with the stereoscopic endoscope were superior (9.2% +/- 9.5%) to those obtained with the open biopsy forceps method (-34.0% +/- 26.8%). These preliminary in vitro results with the stereoscope show considerable promise for the simple and precise three dimensional measurement of gastrointestinal lesions and warrant human clinical trials. PMID- 8454142 TI - Sigmoidoscopy training for nurses and resident physicians. AB - Five gastrointestinal nurses (three licensed practical nurses and two registered nurses) and five resident physicians were enrolled in a sigmoidoscopy training protocol. Patients referred for a screening sigmoidoscopy were randomized to have the procedure performed by a nurse or a resident. Objective criteria for proficiency were depth of endoscope insertion, procedure time, and identification of anatomic landmarks and pathologic lesions; subjective criteria included thoroughness and the need for assistance. Four nurses and all of the residents were deemed proficient at a mean of 20 procedures in both groups. One registered nurse did not achieve proficiency after 35 procedures; this determination was based on subjective criteria. Insertion depth and identification of normal anatomy improved with experience. Trainees missed 1.4% of pathologic lesions, and no complications were observed. Nurses can be trained to perform a screening sigmoidoscopy in a safe and effective manner, with results similar to those for doctors. PMID- 8454144 TI - Endoscopic evaluation of the therapeutic effect of sclerotherapy for esophageal varices. AB - The rebleeding rate after endoscopic injection sclerotherapy was studied in 237 patients with esophageal varices, and the optimal outcome of treatment was determined. Two new categories, RC(2-) and F0, were added to the classification scheme of endoscopic findings of varices in Japan. RC(2-) represents a state in which no veins, not even small vessels, are observed by endoscopy after endoscopic injection sclerotherapy, and F0 represents a state in which no localized venous dilations in the esophagus exist. The criteria for defining the other categories were not altered, and the R-C sign was expressed as RC(2-), RC( ), or RC(+); the degree of dilation was classified as F0 to F3. By combining the R-C sign and the F number, endoscopic findings were classified 1 to 4 weeks after endoscopic injection sclerotherapy into groups designated RC(2-)F0, RC(-)F0, RC( )F1, and RC(+)F1-RC(+)F2. The four groups were observed to determine the incidence of esophageal stricture and rebleeding. In the RC(2-)F0 group, the incidence of stricture was high, but the rebleeding rate was low. In the RC(-)F0 group, both the incidence of stricture and rebleeding rate were low. We conclude that the optimal outcome of endoscopic injection sclerotherapy is RC(-)F0. PMID- 8454143 TI - A comparison of winged steel needles and Teflon cannulas in maintaining intravenous access during gastrointestinal endoscopy. AB - We have conducted a prospective study in 142 consecutive patients undergoing either gastroscopy or colonoscopy. The patients were randomized to have either a 23-gauge winged steel needle or a 23-gauge Teflon cannula inserted. The two groups were well matched, with 71 patients receiving each device. Intravenous access was achieved in every case. The steel needle was inserted at the first attempt in 65 of 71 cases (91.6%) compared with 67 of 71 cases (94.4%) for the Teflon cannula. Extravasation occurred in only 1 of 71 cases (1.4%) with Teflon cannulas compared with 18 of 71 cases (25.5%) of steel needle use (p < 0.01). Additionally, no Teflon cannula blocked completely, whereas 1 of 71 steel needles (1.4%) did so. Only 1 of 71 (1.4%) of the Teflon cannulas became difficult to flush compared with 12 of 71 steel needles (16.9%). The Teflon cannula was as easy to insert and provided significantly more reliable intravenous access than the steel needle. PMID- 8454145 TI - Can advanced age influence the characteristics of peptic gastric ulcer? Italian Multicenter Study Group for Gastric Ulcer. AB - Do gastric ulcers in older patients bear the same characteristics as gastric ulcers in younger patients? To seek an answer, a multicenter study group in Italy compared gastric ulcers in a group of 124 patients older than 60 years with those in a group of 162 patients younger than 50 years. The only difference observed was that gastric ulcers in the older group tended to be larger. The rate of healing, in response to famotidine, was the same. PMID- 8454146 TI - Intraoperative endoscopic sphincterotomy for common bile duct stones during laparoscopic cholecystectomy. PMID- 8454147 TI - Endoscopic mucosal resection with a cap-fitted panendoscope for esophagus, stomach, and colon mucosal lesions. PMID- 8454148 TI - Simple modification of a pancreatic duct stent to prevent proximal migration. PMID- 8454149 TI - Endoscopic implantation of expandable metal Z stents for malignant biliary strictures. PMID- 8454150 TI - Selective common bile duct cannulation can be simplified by the use of a standard papillotome. PMID- 8454151 TI - Improving the withdrawal phase of Sonde enteroscopy with the "push-away" method. PMID- 8454152 TI - Photodynamic therapy for treatment of early adenocarcinoma in Barrett's esophagus. PMID- 8454153 TI - Enteroscopy for unexplained iron-deficiency anemia: identifying the patient with sprue. PMID- 8454154 TI - Villous adenoma of the pancreatic duct mimicking a stone: pancreatoscopic diagnosis. PMID- 8454155 TI - Aneurysmal dilation of the abdominal aorta: a rare cause of obstructive jaundice. PMID- 8454156 TI - Diffuse submucosal cysts of the stomach with multifocal gastric carcinoma: diagnostic role of endoscopic ultrasonography. PMID- 8454157 TI - Endoscopic treatment of problems encountered after laparoscopic cholecystectomy [corrected]. AB - With the advent of laparoscopic cholecystectomy, a number of patients with various postprocedure problems have been referred for endoscopic management. Thirty-five patients were evaluated. The group included 26 women and 9 men, ages 24 to 90 years (mean, 50 years). Twenty-five patients with retained common bile duct stones were successfully treated with endoscopic sphincterotomy and balloon or basket removal. Three patients with bile duct strictures had balloon dilation and endoprosthesis placement and were free of signs of obstruction on 9-month follow-up. Bile leaks were treated successfully with endoscopic sphincterotomy and endoprosthesis placement. Two patients with bile duct leaks and biloma formation required percutaneous or surgical drainage in addition to endoscopic treatment. Three patients had more than one complication. Two patients had strictures with retained stones above the stricture; dilation of the stricture was performed and the stones were removed. One patient with the complication of biliary leak and a long, irregular stricture was treated temporarily by sphincterotomy and stent placement while awaiting surgery. Therapeutic biliary endoscopy is a valuable, minimally invasive alternative to surgery in patients with problems arising after laparoscopic cholecystectomy. PMID- 8454158 TI - Endoscopic stent placement for biliary leak from an accessory duct of Luschka after laparoscopic cholecystectomy. PMID- 8454159 TI - Anomalous pancreaticobiliary communication in a neurofibromatosis patient. PMID- 8454160 TI - Successful endoscopic treatment of a fistula between the common bile duct and neobladder. PMID- 8454161 TI - Laparoscopic cholecystectomy: what to do with the common duct. PMID- 8454162 TI - Effect of 17 beta-estradiol on somatic and germ cell subpopulations in the ovary of the newly hatched chick. AB - The involvement of estrogens in avian ovary differentiation and morphogenesis has been previously demonstrated by several authors. The aim of the present study is to provide evidence regarding which cell subpopulations of the ovary are target cells for 17 beta-estradiol during chick development. White Leghorn chick embryos received 200 ng of the hormone or the vehicle on the chorioallantoic membrane at 11, 13, and 15 days of incubation. Within 24 hr after hatching, the left ovary was processed for total cell count, study of the meiotic prophase of oocytes, and the morphometric evaluation of the cortical and the medullary regions of the ovary. Germ cell number was not modified by the treatment. Similarly, no changes were observed in the stage of the prophase and the cellular area of oocytes. The total number of somatic cells was increased in the newly hatched chick ovary treated with 17 beta-estradiol. The number of undifferentiated cells in the juxtacortical medulla was higher in the treated ovary than in the control group. Moreover, the pregranulosa cells of the cortical region were hypertrophied in the 17 beta-estradiol treated ovary. However, no changes were observed in the typical steroidogenic cells after the estrogen treatment. In conclusion, two subpopulations of somatic cells are estrogen target cells in the prefollicular chicken ovary: the pregranulosa cells of the ovarian cortex and the undifferentiated cells in the juxtacortical medulla. PMID- 8454163 TI - Goldfish calcitonin: purification, characterization, and hypocalcemic potency. AB - A novel teleost calcitonin was isolated from the goldfish, Carassius auratus, and its amino acid sequence was determined to be H-Cys-Ser-Ser-Leu-Ser-Thr-Cys-Val Leu-Gly- Lys-Leu-Ser-Gln-Glu-Leu-His-Lys-Leu-Gln-Thr-Tyr-Pro-Arg-Thr-Asn-Val-Gly- Ala-Gly-Thr-Pro-NH2. The structure of goldfish calcitonin (gCT) was similar to that of salmon calcitonin (sCT) but differed from the latter at positions 3, 27, and 29. The hypocalcemic activity of gCT was estimated to be 3,470 IU/mg by the standardized rat bioassay method, compared with a value of 3,500 IU/mg for sCT. After administration of gCT to young goldfish, the serum Ca concentration was significantly lower in some cases than in controls. However, in other cases no such difference was recognized. PMID- 8454164 TI - Influence of calcium and vitamin D deficient diet on calcitonin gene expression in the ultimobranchial cells of the developing chicken. AB - Recently hatched chickens were fed a vitamin D and calcium deficient diet for 4 weeks. Calcitonin (CT) biosynthesis in the ultimobranchial glands (UBG) was studied during the treatment by means of in situ hybridization of specific CT mRNAs and immunocytochemical detection of the CT intracellular stores. Circulating CT levels were measured by radioimmunoassay. Within 1 week of the start of treatment, the deficient animals had significantly lowered plasma calcium concentrations and a dramatic fall of plasma CT levels, but the UBGs were not much affected. From week 2 to week 4, the UBG underwent a gradual atrophy. The tissue became lacunar due to the presence of an abnormally developed cystic component. Although calcemia returned to normal at week 4, the cellular endocrine cords were dramatically reduced, corresponding to the undetectable circulating CT levels. However, the UB glands always contained persistent CT-secreting cells, mainly at the periphery of the tissue or in contact with enlarged parathyroid tissue inclusions. These endocrine UB cells contained large amounts of hybridizable CT mRNA and immunodetectable stores of the mature hormone, and their ultrastructural features were quite unaffected compared to normal ones. Thus, we conclude that, in the chicken, severe calcium malnutrition led to a striking reduction of CT biosynthesis in the UB glands by decreasing the number of secretory cells and not by triggering modifications of the biosynthetic activity of the UB endocrine cells. PMID- 8454165 TI - Territorial aggressiveness and its relation to the endocrine system in the pied flycatcher. AB - Behavioral and endocrine responses were studied following simulated territorial intrusions performed at two different stages in the breeding cycle (pre-nest building and nestling period) of the pied flycatcher (Ficedula hypoleuca). Only 45% of the unpaired territorial males from the pre-nest-building period defended their territories by attacking the decoy. After the experimental intrusion unpaired males attacking the decoy had significantly higher plasma testosterone levels than nonattacking unpaired males. Plasma corticosterone levels were significantly higher in both attacking and nonattacking unpaired males than in control males. There were no differences in body size between attacking and nonattacking males. The attacking paired males and paired control males, however, had significantly lower fat depots than other males. The endocrine system of the male pied flycatcher responded within 1 day to the settlement of a female in the territory in that plasma testosterone levels of paired control males were significantly higher than those in unpaired territorial control males. The proportions of attacking males increased significantly (up to 80%) once a female had settled. Unlike in unpaired territorial males, testosterone levels in paired males that attacked the decoy were similar to those in non-attacking males and to those in paired control males after a simulated territorial intrusion. Data suggest that the high testosterone levels are related to territorial aggressiveness and not to sexually related events such as mate-guarding or singing. Forty-five percent of the males from the nestling period did attack the decoy. Despite the strong behavioral response these attacks had no effects on plasma testosterone or corticosterone levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454166 TI - A distinct diurnal rhythm in hydroxyindole-O-methyltransferase (HIOMT) activity in the male albino rat. AB - Pineal hydroxyindole-O-methyltransferase (HIOMT) has been reported to show a diurnal rhythm activity in the rat, although this is not fully confirmed. The present study reexamines this issue and reports a distinct diurnal rhythm in rat pineal HIOMT. Peak enzyme activity occurs 5 hr after the onset of darkness, followed by two lesser bursts of activity preceding each change in the photoperiod. The approximately 18-fold increase in methylating capacity at night represents the greatest variation in HIOMT activity thus far reported in the rat and may be attributed to the age, weight, and housing regimen of the animals used. PMID- 8454167 TI - Effect of reproductive condition on luteinizing hormone and prolactin release induced by electrical stimulation of the turkey hypothalamus. AB - In the turkey, the onset of incubation behavior is associated with decreased luteinizing hormone (LH) and increased prolactin (PRL). This study was designed to clarify the contribution of the hypothalamus and the anterior pituitary to the changes in plasma LH during the reproductive cycle of the turkey. Plasma LH and PRL were measured in anesthetized turkey before, during, and after electrical stimulation in the median eminence. In one experiment, luteinizing hormone releasing hormone (LHRH; 4 micrograms/kg) was injected intramuscularly 30 min after termination of electrical stimulation, and blood samples were obtained 5, 10, 20, and 30 min after injection. Electrical stimulation in the median eminence significantly increased (P < 0.05) plasma LH of laying (LAY), nest-deprived, previously incubating (NEST DEP), and photorefractory (REFRAC) hens, but not of photosensitive short-day (SHORT DAY) birds (P > 0.05). Plasma LH of LAY hens peaked at 4.06 +/- 0.78 ng/ml from a prestimulation baseline of 2.30 +/- 0.21 ng/ml and that in NEST DEP birds increased from 1.08 +/- 0.18 ng/ml to 2.57 +/- 0.53 ng/ml. Administration of LHRH increased plasma LH levels in SHORT DAY, LAY, and NEST DEP hens with the increase being 2.0-, 2.5-, and 6.1-fold, respectively. Electrical stimulation in the median eminence increased plasma PRL (P < 0.05) in all the reproductive groups tested, with peak response being greatest for NEST DEP birds (661 +/- 126 ng/ml) followed by LAY (317 +/- 26 ng/ml), REFRAC (50 +/- 7 ng/ml), and SHORT DAY (39 +/- 12 ng/ml) hens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454168 TI - Changes in plasma androgen levels associated with changes in male reproductive behavior in a brood cycling marine fish. AB - Like many paternal-caring fishes, male garibaldi (Hypsypops rubicundus) exhibit changes in reproductive behavior during the course of a brood cycle. The purpose of this study was to compare plasma levels of testosterone and 11 ketotestosterone among males in different phases of the brood cycle. These phases are characterized by differences in male courtship, nest maintenance, and egg fanning behavior. Blood samples were taken from wild-caught males, and plasma androgen levels were measured using radioimmunoassay techniques. Androgen levels among males in different phases of the brood cycle were concordant with differences in courtship behavior and also showed a general, positive correspondence with nest maintenance behavior. Levels were nearly inversely related to egg fanning rates. These relationships were independent of seasonal or population level environmental effects. These data suggest a strong three-way relationship among androgen levels, reproductive behavior, and stimuli associated with the progressing brood cycle. PMID- 8454169 TI - GnRH-induced desensitization of in vitro luteinizing hormone secretion in the turtle, Trachemys scripta. AB - Gonadotropin-releasing hormone (GnRH)-induced desensitization of pituitary luteinizing hormone (LH) secretion in female turtles (Trachemys scripta) was investigated by in vitro superfusion of whole or hemipituitaries with the endogenous forms of the peptide. In sub-adults, LH secretion was rapidly attenuated (desensitized) by both prolonged and pulsatile treatments of chicken II GnRH (cII-GnRH), but pulsatile GnRH administration was more effective than prolonged administration in stimulating LH release. Prolonged administration of chicken I GnRH (cI-GnRH) also desensitized LH secretion; cI-GnRH was slightly less potent than cII-GnRH. GnRH-induced attenuation of LH secretion was not the result of tissue deterioration or depletion of releasable LH: GnRH responsiveness of desensitized pituitaries was fully restored after 4 hr of in vitro recovery, and further LH secretion was induced by tetraethylammonium chloride, a membrane depolarizing agent, in the desensitized glands; TRH-stimulated TSH release did not show desensitization in the same glands. Pituitaries from most adult (vitellogenic) females failed to respond to GnRH challenges; however, when responsive, adult pituitaries also desensitized under prolonged GnRH stimulation and were more resistant to GnRH-induced desnsitization under pulsatile GnRH treatments. Current results show that adult T. scripta typically display lower GnRH sensitivity than the subadults; the latter are like mammals, birds, and goldfish in their susceptibility to desensitization by both forms of endogenous GnRH. PMID- 8454170 TI - Estrogen responsiveness of vitellogenin gene expression in rainbow trout (Oncorhynchus mykiss) kept at different temperatures. AB - We have examined the effect of ambient water temperature on the ability of juvenile rainbow trout to respond to estradiol (E2) injection with vitellogenin (Vg) synthesis. Vg appeared in serum within 24 hr of E2 injection in fish kept at 15 degrees and rose to 70 mg/ml over a 10-day treatment period during which four injections of E2 were given. A group of fish kept at 9 degrees responded more slowly to the same multiple injection protocol and showed Vg accumulation of only 8.9 mg/ml on the 10th day. Hepatic Vg mRNA levels accumulated more rapidly and extensively in animals treated and kept at 15 degrees than at 9 degrees; however, differences in serum Vg concentrations could not simply be attributed to differences in Vg mRNA levels. The ratio of serum Vg:Vg mRNA increased steadily over the treatment period, especially in the 15 degrees group, suggesting greater efficiency or capacity for translation and/or processing of the Vg protein at the higher temperature. Examination of hepatic nuclear estrogen receptor (ER) concentrations revealed a three- to five-fold increase in high-affinity E2 binding activity within the first 24 hr after injection in both temperature groups. Nuclear ER levels remained elevated to roughly the same extent in both groups throughout the 10-day period. Differences in nuclear ER concentrations and serum E2 concentrations could not account for the large differences in Vg mRNA and protein levels between the two temperature groups. Furthermore, a single injection of E2 at 15 degrees was able to induce higher levels of Vg mRNA and protein than multiple injections at 9 degrees. We suggest that temperature modulates the responsiveness of the liver to E2 at stages which are independent of E2 or ER concentrations. PMID- 8454171 TI - Biological activity of alligator, avian, and mammalian insulin in juvenile alligators: plasma glucose and amino acids. AB - The biological activity of alligator, turkey, and bovine insulin on plasma glucose and plasma amino acids was tested in fasted juvenile alligators. Preliminary experiments showed that the stress associated with taking the initial blood sample resulted in a hyperglycemic response lasting more than 24 hr. Despite repeated bleedings no additional hyperglycemic events occurred, and blood glucose declined slowly over the next 7 days. Under these conditions the smallest dose of insulin eliciting a hypoglycemic response was 40 micrograms/kg body wt. A dose of 400 micrograms/kg body wt of either alligator or bovine insulin caused a pronounced hypoglycemia by 12 hr postinjection. Maximum decline in plasma glucose occurred at 24 to 36 hr with a slow return to control levels by 120 hr. There were no significant differences in the hypoglycemic responses to any of the three insulins tested. The decline in plasma amino acids was much more rapid than the decline in plasma glucose in response to insulin. Even at the 40 micrograms/kg body wt dose a significant difference from saline-injected control was seen at 2 hr postinjection. Maximum decline in plasma amino acids occurred at 8 to 12 hr with a return to baseline by 36 hr. These results show that the relatively conservative changes in the sequence of alligator insulin (three amino acid substitutions in the B-chain compared with that of chicken) have little effect on biological activity and that alligator insulin receptors do not appear to discriminate among the three insulins. PMID- 8454172 TI - Testosterone induced growth of the oviduct in the frog, Rana pipiens: evidence for local aromatization. AB - Ovariectomized and immature frogs were injected with estradiol, testosterone, dihydrotestosterone (DHT), or a combination of estradiol with one of the androgens. Controls were treated with oil. Dry oviduct weights were compared across groups. Ovariectomized animals treated with testosterone or estradiol plus testosterone had the largest oviducts, whereas oviducts were slightly smaller in groups treated with estradiol alone. DHT had no effect in mature ovariectomized animals and only a very slight effect in immature animals. Protein content of oviducts showed little significant difference between groups. These results suggest that oviduct growth in testosterone-treated animals may be due to aromatization of testosterone to estradiol. To test this hypothesis, oviduct tissue was incubated in vitro with or without testosterone. Estradiol levels in the medium were much higher when testosterone was present, indicating that aromatization can occur in the oviduct. PMID- 8454173 TI - Binding of aldosterone by epidermal cytosol in the tail of bullfrog larvae. AB - Characteristics of aldosterone binding by epidermal cytosol in the tail of the larval bullfrog were investigated. Temperature-dependent binding experiments showed that the specific binding of [3H]aldosterone to the tail cytosol was thermolabile. A 3-hr incubation at 0 degrees was the optimum assay condition required for reaching equilibrium. Separation of bound and free hormone was performed using a hydroxylapatite method. Specific binding of aldosterone was observed in the tail epidermis but not in the tail mesenchyme. Saturation analysis revealed that specific binding of [3H]aldosterone to the epidermal cytosol reached maximum between 20 and 40 nM. Scatchard analysis for the cytosol of the tail epidermis yielded a straight line with a dissociation constant (Kd) of 7.0 nM and the maximum number of binding sites (Bmax) of 56.4 fmol/mg protein. Sucrose density gradient analysis of crude cytosol revealed a specific peak of radioactivity in the 8-9 S area. Steroid-binding specificity revealed a significant displacement of the [3H]aldosterone by radioinert aldosterone and, to a lesser extent, by cortisol, whereas 17 beta-estradiol and testosterone competed very poorly. However, corticosterone and dexamethasone, glucocorticoids in mammals, were better competitors of the aldosterone binding, whereas ZK91587, a selective synthetic antagonist for mineralocorticoid receptor in mammals, scarcely inhibited the aldosterone binding. These results suggest that the aldosterone-binding site may also be a corticosterone receptor and that there may be no other receptors specific for aldosterone at least in the tail epidermis. PMID- 8454174 TI - Testosterone alters the immune response of chinook salmon, Oncorhynchus tshawytscha. AB - We examined the effects of the high concentrations of sex steroid hormones detected in the plasma of sexually maturing chinook salmon (Oncorhynchus tshawytscha) on the functioning of the immune system. Leukocytes from the anterior kidney of juvenile spring chinook salmon were incubated in the presence of steroid, and their ability to form specific antibody-producing cells (plaque forming cells) was used as a measure of immunocompetence. Testosterone and cortisol, but not 17 beta-estradiol or aldosterone, were found to significantly reduce the plaque-forming response in vitro. Testosterone and cortisol administered together had a significantly greater effect than did either administered alone. The plaque-forming response was significantly affected by season. The magnitude of the steroid-induced immunosuppression was reduced during winter and increased again in spring. PMID- 8454175 TI - Purification and characterization of insulin and the C-peptide of proinsulin from Przewalski's horse, zebra, rhino, and tapir (Perissodactyla). AB - Within the order Perissodactyla, the primary structure of insulin has been strongly conserved. Insulin from Przewalski's horse and the mountain zebra (suborder Hippomorpha) is the same as that from the domestic horse and differs from insulin from the white rhinoceros and mountain tapir (suborder Ceratomorpha) by a single substitution (Gly-->Ser) at position 9 in the A-chain. A second molecular form of Przewalski's horse insulin isolated in this study was shown to represent the gamma-ethyl ester of the Glu17 residue of the A-chain. This component was probably formed during the extraction of the pancreas with acidified ethanol. The amino acid sequence of the C-peptide of proinsulin has been less well conserved. Zebra C-peptide comprises 31 amino acid residues and differs from Przewalski's horse and domestic horse C-peptide by one substitution (Gln30-->Pro). Rhino C-peptide was isolated only in a truncated form corresponding to residues (1-23) of intact C-peptide. Its amino acid sequence contains three substitutions compared with the corresponding region of horse C peptide. It is postulated that the substitution (Pro23-->Thr) renders rhino C peptide more liable to proteolytic cleavage by a chymotrypsin-like enzyme than horse C-peptide. C-peptide could not be identified in the extract of tapir pancreas, suggesting that proteolytic degradation may have been more extensive than in the rhino. In contrast to the ox and pig (order Artiodactyla), there was no evidence for the expression of more than one proinsulin gene in the species of Perissodactyla examined. PMID- 8454176 TI - Cloning of the replication region on the bacteriocinogenic plasmid pRJ9 of Staphylococcus aureus. AB - A 5.8-kb ClaI fragment of pRJ9, a bacteriocinogenic plasmid of Staphylococcus aureus, was cloned in the unique ClaI site of pRJ5. The recombinant plasmid obtained, pRJ23, failed to confer bacteriocin production and immunity to bacteriocin on host cells. The cloned fragment was shown to contain the complete replicon of pRJ9. Attempts to clone the 4.4-kb ClaI fragment of pRJ9 were unsuccessful, apparently due to the inactivation of the basic replicon of the cloning vector. Therefore, plasmid pRJ5 cut at its ClaI site appears to be a suitable vector for cloning replication regions of plasmids that can replicate in S. aureus. PMID- 8454177 TI - Expression of beta-galactosidase from a hybrid promoter:operator element in Escherichia coli. AB - A hybrid trpPO:lacO regulatory sequence was cloned upstream of a promoterless lacZ gene and recombined onto a lambda bacteriophage. Escherichia coli lysogens representing the four possible phenotypes for lacI and trpR were constructed and the synthesis of beta-galactosidase was assayed under various growth conditions. The results illustrated that both control elements could be efficiently and independently regulated by the addition or omission of appropriate accessory molecules. PMID- 8454178 TI - Covalently immobilized DNA plate for luminometric DNA-DNA hybridization to identify viridans streptococci in under 2 hours. AB - Single-stranded chromosomal DNA was covalently bound to a microdilution plate and used for quantitative DNA-DNA hybridization. After 30 min, hybridized DNA was quantitatively detected by alkaline phosphatase and a chemiluminescent substrate. This method was successfully used for the rapid identification of viridans streptococci. PMID- 8454179 TI - Distribution of the zot (zonula occludens toxin) gene among strains of Vibrio cholerae 01 and non-01. AB - The distribution of the zot gene that encodes the zonula occludens toxin, a newly described toxin of Vibrio cholerae, among clinical, environmental and food isolates of V. cholerae 01 and non-01 was investigated. Both the zot gene and the ctx gene that encode cholera toxin were found in 247 of 257 clinical strains and 62 of 415 environmental or food isolates of V. cholerae 01. The zot gene, but not the ctx gene was found in 37 strains (one clinical strain and 36 environmental or food isolates). In addition, two of 31 clinical strains and six of 98 environmental or food isolates of V. cholerae' non-01 possessed both the zot gene and the ctx gene. These results demonstrated the predominantly concurrent occurrence of the zot gene and ctx genes among strains of V. cholerae 01 which suggests a possible synergistic role of ZOT in the causation of acute dehydrating diarrhea produced by V. cholerae 01. PMID- 8454180 TI - Serotype F double- and triple-converting phage insertionally inactivate the Staphylococcus aureus beta-toxin determinant by a common molecular mechanism. AB - The precise molecular mechanism of Staphylococcus aureus beta-toxin inactivation by the serotype F triple-converting phage phi 42, phi A1 and phi A3 was investigated. Sequence analysis of the phi 42 (attP) and Staphylococcus aureus (attB) attachment sites and the left (attL) and right (attR) chromosomal/bacteriophage DNA junctions of individual lysogens, each harbouring a triple-converting phage, revealed the presence of a common 14-bp core sequence in all four sites. These findings indicate that the genomes of the triple-converting phage integrate into the 5'-end of the beta-toxin gene (hlb) by a site- and orientation-specific mechanism identical to that previously described for the serotype F double-converting phage phi 13. PMID- 8454181 TI - Levels of plasma membrane H(+)-ATPase do not change during growth and morphogenesis of Candida albicans. AB - A transient rise in the PM-ATPase activity was observed at the time of commitment of Candida albicans cells to either bud or hyphal formation. However, the changes in PM-ATPase activity did not correlate with the level of enzyme protein detected by ELISA. It was found to be fairly constant during differentiation, implying that there was no de novo synthesis of the protein. Post-translational modification(s) of enzyme protein is suggested to account for variation in PM ATPase activity during morphogenesis. PMID- 8454182 TI - Deletion analysis of the essentiality of penicillin-binding proteins 1A, 2B and 2X of Streptococcus pneumoniae. AB - An internal fragment from each of the penicillin-binding protein (PBP) 1A, 2B and 2X genes of Streptococcus pneumoniae, which included the region encoding the active-site serine residue, was replaced by a fragment encoding spectinomycin resistance. The resulting constructs were tested for their ability to transform S. pneumoniae strain R6 to spectinomycin resistance. Spectinomycin-resistant transformants could not be obtained using either the inactivated PBP 2X or 2B genes, suggesting that deletion of either of these genes was a lethal event, but they were readily obtained using the inactivated PBP 1A gene. Analysis using the polymerase chain reaction confirmed that the latter transformants had replaced their chromosomal copy of the PBP 1A gene with the inactivated copy of the gene. Deletion of the PBP 1A gene was therefore tolerated under laboratory conditions and appeared to have little effect on growth or susceptibility to benzylpenicillin. PMID- 8454183 TI - Reduced ribosomal thermal denaturation in Listeria monocytogenes following osmotic and heat shocks. AB - Increased thermotolerance of Listeria monocytogenes induced by exposure to a high NaCl concentration or a sublethal heat shock was concurrent with increased thermal stability of the 30S ribosomal subunit as measured by differential scanning calorimetry. It is proposed that protection of the 30S subunit is a critical mechanism for increased thermotolerance. PMID- 8454184 TI - Low-nutrient induction of abnormal chlamydial development: a novel component of chlamydial pathogenesis? AB - The intracellular development of chlamydiae in McCoy cells incubated in Eagle's minimal essential medium lacking all 13 amino acids was examined both by fluorescence and electron microscopy and by infectivity titration. Aberrant development occurred in almost all inclusions of strains of Chlamydia trachomatis and C. psittaci with the production of abnormal forms which differed in size, shape and internal structure from normal reticulate and elementary body forms. Detailed analysis of the response of C. trachomatis L2 strain 434 to graded reductions in amino acid level showed that infectivity was reduced and morphological abnormality increased as amino acid concentrations were lowered from 33 to 0% of amino acids present in minimal essential medium. Reversion of inclusions to normal and reappearance of infectious forms occurred on restoration of amino acids and further incubation. It is suggested that aberrant development may account for the presence in vivo of non-cultivable chlamydiae and that such development can arise via tryptophan deprivation mediated by local release of interferon gamma. PMID- 8454185 TI - Mycoplasma cells stimulate in vitro activation of plasminogen by purified tissue type plasminogen activator. AB - In an in vitro direct assay with tissue-type plasminogen activator (tPA), plasminogen and the chromogenic substrate S-2251, the ability of Mycoplasma fermentans KL4 to stimulate tPA-mediated activation of plasminogen to plasmin was studied. Mycoplasma cells markedly enhanced the activation of plasminogen by tPA in a concentration-, temperature- and pH-dependent manner. Nonidet P-40 (0.01%), sonication, and freezing and thawing of the cells substantially increased the stimulatory effect of mycoplasma on tPA activity. In contrast, the activation of plasminogen by urokinase was refractory to mycoplasma cells. The mycoplasma mediated stimulation of tPA activity was prevented by epsilon-aminocaproic acid (EACA), a lysine analogue known to block lysine-binding sites (LBS) in plasminogen and tPA. Among several Mycoplasma fermentans strains tested, incognitus strain demonstrated the highest stimulation activity. These results suggest that mycoplasma cells interact with LBS in tPA and plasminogen to enhance plasminogen activation. PMID- 8454186 TI - Increased expression of the plasmid-determined 2,3-dihydroxybiphenyl dioxygenase gene in strains of Escherichia coli, Pseudomonas putida and Pseudomonas aeruginosa. AB - A 6.5-kb EcoRI fragment containing the gene encoding 2,3-dihydroxybiphenyl dioxygenase from the plasmid pBS312 was cloned into broad host range plasmid RSF1010 and expressed in Escherichia coli, Pseudomonas putida and Pseudomonas aeruginosa strains. The increased expression of the gene was orientation dependent and probably due to the transcription read through from the streptomycin promoter of the vector. Subcloning experiments of the PstI fragments of pBS312 plasmid using vector pBR322 revealed that the bphC gene encoding 2,3 dihydroxybiphenyl dioxygenase is localized on the 2.1-kb fragment. In Escherichia coli JM109, transformed by the plasmid pBS314 carrying the 2.1-kb insert in orientation which allowed expression of the bphC gene from the ampicillin promoter of pBR322, the enzyme activity of 2,3-dihydroxybiphenyl dioxygenase was ten times higher than that in parental strain Pseudomonas putida SU83. The results presented show the first case of the increased expression of Pseudomonas degradative gene in Escherichia coli. PMID- 8454187 TI - Heterogeneity in the molecular species of heat-stable enterotoxin of Vibrio cholerae non-O1 expressed by Escherichia coli carrying the cloned toxin gene. AB - The biological activity of the heat-stable enterotoxin of Vibrio cholerae non-O1 (NAG-ST) was found to be predominantly associated with the periplasmic extract (about four-fold higher than the culture supernatant) of a recombinant E. coli (JM109) strain carrying the NAG-ST toxin gene. Four molecular species of NAG-ST, two each from the periplasmic extract and culture supernatant of JM109, were purified. Amino acid sequence analysis of the four NAG-ST peptides isolated by HPLC revealed that they all differed from that of the mature 17-amino acid residue NAG-ST released by V. cholerae non-O1. The M(r)-values of the peptides obtained from the periplasmic extract were 4331 and 2785, while those recovered from the culture supernatant were 3154 and 2785. It thus appears that V. cholerae NAG-ST is synthesized as larger molecules in the recombinant E. coli strain. The differences in sizes of the exported NAG-ST molecule could relate to differences in the enzyme cleavage system between E. coli and V. cholerae. PMID- 8454188 TI - Characterization of mutations that overcome the toxic effect of glucose on phosphoglucose isomerase less strains of Saccharomyces cerevisiae. AB - Glucose inhibits growth of yeast phosphoglucose isomerase mutants in permissive media. Mutants insensitive to this effect were isolated by selection on media containing 2% fructose + 2% glucose. A nuclear, monogenic, recessive mutation named rgl was responsible for this phenotype. The mutants isolated belonged to two complementation groups and have been termed rgl1 and rgl2. When the double mutants were grown on fructose, fermentation of fructose or glucose was similar to that of the parental pgi strain but was not measurable when grown on fructose+glucose. Under these conditions, respiration of glucose and to a lesser extent of fructose was enhanced. The double mutants pgi rgl did not grow on fructose+glucose in the presence of antimycin A or ethidium bromide and their cytochrome oxidase was no longer sensitive to glucose repression. The results are interpreted as an indication that in the double mutants the glucose may be channeled through the pentose phosphate pathway to respiration. PMID- 8454189 TI - Formation of cross-fractures in cellulose microfibril structure by an endoglucanase-cellobiohydrolase complex from Trichoderma reesei. AB - An endoglucanase-cellobiohydrolase complex from Trichoderma reesei culture fluids was purified by means of preparative isoelectric focusing. The cellulase complex had a common apparent isoelectric point (pI) of 3.8. Beyond this pI, the electrophoretic mobilities of endoglucanase and cellobiohydrolase were different under conditions of titration curves. The effect of this endoglucanase cellobiohydrolase complex on Sinapis cellulose microfibril ultrastructure was observed by transmission electron microscopy after metal shadowing of the specimen. By the action of this cellulase complex, the microfibril structure was converted into an amorphous form of cellulose. Moreover, the hydrolase complex induced visible cross-fractures within the cellulose microfibril structure. The mean cellulose microfibril length of 1.2 microns was reduced to 0.9 microns in the presence (12 h) of this cellulase complex by the formation of shorter microfibril fragments. PMID- 8454190 TI - Analysis of the Spirochaeta aurantia flaA gene and transcript. AB - The flaA gene, which codes for the Spirochaeta aurantia flagellar filament outer layer polypeptide, FlaA, was cloned, sequenced and analysed. The gene appears to be transcribed into a monocistronic mRNA from a sigma 70-like promoter. The translational start is 31 base pairs after the start of the transcript, the open reading frame is 1011 base pairs, and a rho-independent-like transcription terminator sequence begins about 19 base pairs after the translational stop codon. The deduced amino acid sequence of the S. aurantia FlaA showed 40% identity with the Treponema pallidum FlaA, but these polypeptides did not show a significant similarity to other polypeptides for which sequence information was available. PMID- 8454191 TI - Bioluminescence (lux) expression in the anaerobe Clostridium perfringens. AB - To determine whether bacterial luciferase is expressed in the anaerobe Clostridium perfringens to produce an oxygen-requiring bioluminescence reaction, a suitable plasmid vector possessing the luxA and luxB genes of Vibrio fischeri was constructed and introduced into C. perfringens cells. luxAB were placed under the transcriptional control of the C. perfringens alpha-toxin gene promoter region. Suitable ribosome binding sites were introduced upstream of both genes. Bioluminescence was strongly expressed in C. perfringens transformants. Comparisons of in vivo and in vitro bioluminescence measurements demonstrated that in vivo data constituted a quantitative measure of gene expression. This is the first study to show that luxA and luxB genes can be expressed in an anaerobic bacterium and that bioluminescence can be used as a quantitative reporter system in future in vivo studies of gene expression in C. perfringens. PMID- 8454192 TI - Effect of host lineage on the virulence of Campylobacter jejuni/coli in the chick embryo model. AB - The chorioallantoic membrane (CAM) inoculated chick embryo model was used to study the effect of host lineage on the virulence of Campylobacter jejuni and Campylobacter coli. LD50 values were used to compare the susceptibilities of chick embryos from eight inbred chicken lines to infection by four strains of C. jejuni and one strain of C. coli. Differences in susceptibility were found between inbred chicken lines. These were shown not to be due to maternal antibody status, nor transfer of antibody to the developing embryo. Susceptibility to infection was also found to vary according to the Campylobacter strain used. These results indicate that both the bacterial strain and host lineage of the chicken line used affect resistance to infection in the CAM inoculated chick embryo model. PMID- 8454193 TI - Isolation and characterization of two immunochemically distinct alkaline phosphatases from Pseudomonas aeruginosa. AB - We have isolated two alkaline phosphatases (H-AP and L-AP, for high and low molecular mass, respectively) from Pseudomonas aeruginosa PA01. These two enzymes were found to differ in mobility on sodium dodecyl sulphate polyacrylamide gels (H-AP, M(r) = 51,000 and L-AP, M(r) = 39,500), amino-terminal amino acid sequence and did not cross-react. Both enzymes were active as phosphomonoesterases while only L-AP demonstrated any phosphodiesterase activity. Both enzymes were purified from P. aeruginosa grown in phosphate limiting conditions using the same protocol and were identified in both periplasmic and extracellular locations. A low level of H-AP was produced constitutively whereas L-AP was produced only after induction by reduced phosphate concentration in the growth medium. An L-AP-like enzyme has been previously described, however, this is the first report of a second P. aeruginosa alkaline phosphatase. PMID- 8454194 TI - Cloning and characterization of heat-inducible promoters of Bacillus subtilis. AB - Heat-inducible DNA fragments of Bacillus subtilis were cloned with two different promoter probe vectors. The increased synthesis of the reporter enzymes seemed to be due to a transient increase in the transcription of the encoding genes. The structure of the heat-sensitive promoters resembles the consensus sequence of promoters recognized by the vegetative form of RNA polymerase of B. subtilis. Our results support data in literature that the heat shock response of B. subtilis is regulated by a different mechanism than in Escherichia coli, where alternative sigma factors direct the transcription of heat shock genes. PMID- 8454195 TI - Immobilization of plasminogen on Escherichia coli flagella. AB - The interaction of plasminogen with flagella of Escherichia coli was investigated. Plasminogen bound to flagella purified from E. coli LE392, a commonly used cloning host, and E. coli IH3069, an O25H1 strain isolated from a case of newborn bacteremia. The binding was inhibited by the lysine analog epsilon-aminocaproic acid, suggesting involvement of the lysine-binding Kringle domains of plasminogen in the binding. Purified flagella enhanced the formation of plasmin activity in the presence of tissue-type plasminogen activator; a similar enhancement was observed with flagella-expressing LE392 cells. PMID- 8454196 TI - Long-chain alpha-hydroxy-(omega-1)-oxo fatty acids and alpha-hydroxy-1,omega dioic fatty acids are cell wall constituents of Legionella (L. jordanis, L. maceachernii and L. micdadei). AB - Four long-chain fatty acids, 2-hydroxy-27-oxo-octacosanoic acid (n28:0(2-OH,27 oxo)), 2-hydroxy-29-oxo-triacontanoic acid (n30:0(2-OH,29-oxo)), 2-hydroxy heptacosane-1,27-dioic acid (27:0(2-OH)-dioic) and 2-hydroxy-nonacosane-1,29 dioic acid (29:0(2-OH)-dioic) were identified by GLC-MS analysis in the phenol chloroform-petroleum ether (PCP) extracts of Legionella jordanis, L. maceachernii and L. micdadei indicating that they are constituents of lipopolysaccharide. Moreover, five long-chain fatty acids (28:0(27-OH), 28:0(27-oxo), 30:0(29-oxo), 27:0-dioic and 29:0-dioic) previously identified in L. pneumophila (Moll, H. et al., FEMS Microbiol. Lett., 97 (1992), 1-6) were also found in these species. This is to our knowledge the first report on the existence of long chain 2 hydroxylated (omega-1)-oxo fatty acids and 2-hydroxylated 1,omega-dioic fatty acids. PMID- 8454197 TI - Biosynthesis of glycoproteins in Candida albicans: biochemical characterization of a soluble alpha-mannosidase. AB - Most alpha-mannosidase activity (80%) in C. albicans was found in a soluble form. Addition of protease inhibitors to explore proteolytic release from a particulate cell component during enzyme preparation did not change this distribution. Molecular mass, calculated from gel filtration chromatography, was 417 kDa. Optimum pH was 6.0 with 50 mM Mes-Tris when p-nitrophenyl-alpha-D-mannopyranoside was used as substrate. Optimum temperature was 42 degrees C with either 10 mM phosphate buffer (pH 6.8) or 50 mM Mes-Tris buffer (pH 6.0) and with 4 methylumbelliferyl-alpha-D-mannopyranoside as substrate. Apparent Km values for p nitrophenyl-alpha-D-mannopyranoside and 4-methylumbelliferyl-alpha-D mannopyranoside were 3.3 mM and 0.1 mM, respectively. 1 mM 1-deoxymannojirimycin and 0.3 mM swainsonine inhibited the hydrolysis of 4-methylumbelliferyl-alpha-D mannopyranoside by 67% and 83%, respectively, whereas that of p-nitrophenyl-alpha D-mannopyranoside was only slightly diminished (10-15%). PMID- 8454198 TI - Development of a selective and sensitive polymerase chain reaction assay for the detection of Mycoplasma pirum. AB - A new assay using the polymerase chain reaction to amplify a 173-nucleotide DNA fragment within the 16S ribosomal RNA gene of Mycoplasma pirum has been developed. The assay selectively amplified DNA from all strains of M. pirum tested with a high level of sensitivity, even in a context of human DNA. DNA from other mollicute species, including those closely related to M. pirum, from bacteria phylogenetically close to mollicutes (Clostridium innocuum, C. ramosum and Bacillus subtilis), from Escherichia coli and from human peripheral blood mononuclear cells, did not produce the amplified DNA product specific for M. pirum. PMID- 8454199 TI - Thirty years ago in Genetics: prophage insertion into bacterial chromosomes. PMID- 8454200 TI - Replication-dependent sister chromatid recombination in rad1 mutants of Saccharomyces cerevisiae. AB - Homolog recombination and unequal sister chromatid recombination were monitored in rad1-1/rad1-1 diploid yeast cells deficient for excision repair, and in control cells, RAD1/rad1-1, after exposure to UV irradiation. In a rad1-1/rad1-1 diploid, UV irradiation stimulated much more sister chromatid recombination relative to homolog recombination when cells were irradiated in the G1 or the G2 phases of the cell cycle than was observed in RAD1/rad1-1 cells. Since sister chromatids are not present during G1, this result suggested that unexcised lesions can stimulate sister chromatid recombination events during or subsequent to DNA replication. The results of mating rescue experiments suggest that unexcised UV dimers do not stimulate sister chromatid recombination during the G2 phase, but only when they are present during DNA replication. We propose that there are two types of sister chromatid recombination in yeast. In the first type, unexcised UV dimers and other bulky lesions induce sister chromatid recombination during DNA replication as a mechanism to bypass lesions obstructing the passage of DNA polymerase, and this type is analogous to the type of sister chromatid exchange commonly observed cytologically in mammalian cells. In the second type, strand scissions created by X-irradiation or the excision of damaged bases create recombinogenic sites that result in sister chromatid recombination directly in G2. Further support for the existence of two types of sister chromatid recombination is the fact that events induced in rad1-1/rad1-1 were due almost entirely to gene conversion, whereas those in RAD1/rad1-1 cells were due to a mixture of gene conversion and reciprocal recombination. PMID- 8454202 TI - Mutations in MGI genes convert Kluyveromyces lactis into a petite-positive yeast. AB - Following targeted disruption of the unique CYC1 gene, the petite-negative yeast, Kluyveromyces lactis, was found to grow fermentatively in the absence of cytochrome c-mediated respiration. This observation encouraged us to seek mitochondrial mutants by treatment of K. lactis with ethidium bromide at the highest concentration permitting survival. By this technique, we isolated four mtDNA mutants, three lacking mtDNA and one with a deleted mitochondrial genome. In the three isolates lacking mtDNA, a nuclear mutation is present that permits petite formation. The three mutations occur at two different loci, designated MGI1 and MGI2 (for Mitochondrial Genome Integrity). The mgi mutations convert K. lactis into a petite-positive yeast. Like bakers' yeast, the mgi mutants spontaneously produce petites with deletions in mtDNA and lose this genome at high frequency on treatment with ethidium bromide. We suggest that the MGI gene products are required for maintaining the integrity of the mitochondrial genome and that, petite-positive yeasts may be naturally altered in one or other of these genes. PMID- 8454201 TI - a/alpha-control of DNA repair in the yeast Saccharomyces cerevisiae: genetic and physiological aspects. AB - It has long been known that diploid strains of yeast are more resistant to gamma rays than haploid cells, and that this is in part due to heterozygosity at the mating type (MAT) locus. It is shown here that the genetic control exerted by the MAT genes on DNA repair involves the a1 and alpha 2 genes, in a RME1-independent way. In rad18 diploids, affected in the error-prone repair, the a/alpha effects are of a very large amplitude, after both UV and gamma-rays, and also depends on a1 and alpha 2. The coexpression of a and alpha in rad18 haploids suppresses the sensitivity of a subpopulation corresponding to the G2 phase cells. Related to this, the coexpression of a and alpha in RAD+ haploids depresses UV-induced mutagenesis in G2 cells. For srs2 null diploids, also affected in the error-prone repair pathway, we show that their G1 UV sensitivity, likely due to lethal recombination events, is partly suppressed by MAT homozygosity. Taken together, these results led to the proposal that a1-alpha 2 promotes a channeling of some DNA structures from the mutagenic into the recombinational repair process. PMID- 8454203 TI - Genetic control of pheromones in Drosophila simulans. II. kete, a locus on the X chromosome. AB - The production of Drosophila cuticular hydrocarbons, including contact pheromones, is under polygenic control. To investigate X-linked loci, EMS mutations were induced in Drosophila simulans flies. A mutant strain was discovered which in both sexes show a reduction in the biosynthesis of both 7 tricosene (7-T) the species contact pheromone and all other linear hydrocarbons. The locus controlling this effect, kete, is recessive and was localized to I, 18.5. Unlike a previously identified gene on the second chromosome of this species, Ngbo, kete does not affect the ratio of 7-T:7-pentacosene (7-P). Other reproductive characteristics are also affected, including egg-hatching. However, courtship behaviors in both sexes appear normal. PMID- 8454204 TI - The kl-3 loop of the Y chromosome of Drosophila melanogaster binds a tektin-like protein. AB - Primary spermatocyte nuclei of Drosophila melanogaster exhibit three giant lampbrush-like loops formed by the kl-5, kl-3 and ks-1 Y-chromosome fertility factors. These structures contain and abundantly transcribe highly repetitive, simple sequence DNAs and accumulate large amounts of non-Y-encoded proteins. By immunizing mice with the 53-kD fraction (enriched in beta 2-tubulin) excised from a sodium dodecyl sulfate-polyacrylamide gel loaded with Drosophila testis proteins we raised a polyclonal antibody, designated as T53-1, which decorates the kl-3 loop and the sperm flagellum. Two dimensional immunoblot analysis showed that the T53-1 antibody reacts with a single protein of about 53 kD, different from the tubulins and present both in X/Y and X/O males. Moreover, the antigen recognized by the T53-1 antibody proved to be testis-specific because it was detected in testes and seminal vesicles but not in other male tissues or in females. The characteristics of the protein recognized by the T53-1 antibody suggested that it might be a member of a class of axonemal proteins, the tektins, known to form Sarkosyl-urea insoluble filaments in the wall of flagellar microtubules. Purification of the Sarkosyl-urea insoluble fraction of D. melanogaster sperm revealed that it contains four polypeptides having molecular masses ranging from 51 to 57 kD. One of these polypeptides reacts strongly with the T53-1 antibody but none of them reacts with antitubulin antibodies. These results indicate that the kl-3 loop binds a non-Y encoded, testis-specific, tektin-like protein which is a constituent of the sperm flagellum. This finding supports the hypothesis that the Y loops fulfill a protein-binding function required for the proper assembly of the axoneme components. PMID- 8454205 TI - Isolation of mutations affecting neural circuitry required for grooming behavior in Drosophila melanogaster. AB - We have developed a screen for the isolation of mutations that produce neural defects in adult Drosophila melanogaster. In this screen, we identify mutants as flies unable to remove a light coating of applied dust in a 2-hr period. We have recovered and characterized six mutations and have found that they produce coordination defects and some have reduced levels of reflex responsiveness to the stimulation of single tactile sensory bristles. The grooming defects produced by all six of the mutations are recessive, and each of the mutations has been genetically mapped. We have also used our assay to test the grooming ability of stocks containing mutations that produce known neural defects. PMID- 8454206 TI - Deletion analysis of the selfish B chromosome, Paternal Sex Ratio (PSR), in the parasitic wasp Nasonia vitripennis. AB - Paternal Sex Ratio (PSR) is a "selfish" B chromosome in the parasitoid wasp Nasonia vitripennis. It is transmitted via sperm, but causes supercondensation and destruction of the paternal chromosomes in early fertilized eggs. Because this wasp has haplodiploid sex determination, the effect of PSR is to convert diploid (female) eggs into haploid (male) eggs that carry PSR. Characterizing its genetic structure is a first step toward understanding mechanisms of PSR action. The chromosome is largely heterochromatic and contains several tandemly repeated DNA sequences that are not present on the autosomes. A deletion analysis of PSR was performed to investigate organization of repeats and location of functional domains causing paternal chromosome destruction. Deletion profiles using probes to PSR-specific repetitive DNA indicate that most repeats are organized in blocks on the chromosome. This study shows that the functional domains of PSR can be deleted, resulting in nonfunctional PSR chromosomes that are transmitted to daughters. A functional domain may be linked with the psr22 repeat, but function may also depend on abundance of PSR-specific repeats on the chromosome. It is hypothesized that the repeats act as a "sink" for a product required for proper paternal chromosome processing. Almost all deletion chromosomes remained either functional of nonfunctional in subsequent generations following their creation. One chromosome was exceptional in that it reverted from nonfunctionality to functionality in one lineage. Transmission rates of nonfunctional deletion chromosomes were high through haploid males, but low through diploid females. PMID- 8454207 TI - Recombination suppression by heterozygous Robertsonian chromosomes in the mouse. AB - Robertsonian chromosomes are metacentric chromosomes formed by the joining of two telocentric chromosomes at their centromere ends. Many Robertsonian chromosomes of the mouse suppress genetic recombination near the centromere when heterozygous. We have analyzed genetic recombination and meiotic pairing in mice heterozygous for Robertsonian chromosomes and genetic markers to determine (1) the reason for this recombination suppression and (2) whether there are any consistent rules to predict which Robertsonian chromosomes will suppress recombination. Meiotic pairing was analyzed using synaptonemal complex preparations. Our data provide evidence that the underlying mechanism of recombination suppression is mechanical interference in meiotic pairing between Robertsonian chromosomes and their telocentric partners. The fact that recombination suppression is specific to individual Robertsonian chromosomes suggests that the pairing delay is caused by minor structural differences between the Robertsonian chromosomes and their telocentric homologs and that these differences arise during Robertsonian formation. Further understanding of this pairing delay is important for mouse mapping studies. In 10 mouse chromosomes (3, 4, 5, 6, 8, 9, 10, 11, 15 and 19) the distances from the centromeres to first markers may still be underestimated because they have been determined using only Robertsonian chromosomes. Our control linkage studies using C-band (heterochromatin) markers for the centromeric region provide improved estimates for the centromere-to-first-locus distance in mouse chromosomes 1, 2 and 16. PMID- 8454208 TI - Contrasting roles of interallelic recombination at the HLA-A and HLA-B loci. AB - A statistical study of DNA sequences of alleles at the highly polymorphic class I MHC loci of humans, HLA-A and HLA-B, showed evidence of both large-scale recombination events (involving recombination of exons 1-2 of one allele with exons 3-8 of another) and small-scale recombination events (involving apparent exchange of short DNA segments). The latter events occurred disproportionately in the region of the gene encoding the antigen recognition site (ARS) of the class I molecule. Furthermore, they involved the ARS codons which are under the strongest selection favoring allelic diversity at the amino acid level. Thus, the frequency of recombinant alleles appears to have been increased by some form of balancing selection (such as overdominant selection) favoring heterozygosity in the ARS. These analyses also revealed a striking difference between the A and B loci. Recombination events appear to have occurred about twice as frequently at the B locus, and recombinants at the B locus were significantly more likely to affect polymorphic sites in the ARS. At the A locus, there are well-defined allelic lineages that have persisted since prior to the human-chimpanzee divergence; but at the B locus, there is no evidence for such long-lasting allelic lineages. Thus, relatively frequent interallelic recombination has apparently been a feature of the long-term evolution of the B locus but not of the A locus. PMID- 8454209 TI - Chiasma interference as a function of genetic distance. AB - For many organisms, meiotic double crossing over is less frequent than expected on the assumption that exchanges occur at random with respect to each other. This "interference," which can be almost total for nearby intervals, diminishes as the intervals in which the double crossovers are scored are moved farther apart. Most models for interference have assumed, at least implicitly, that the intensity of interference depends inversely on the physical distance separating the intervals. However, several observations suggest that interference depends on genetic distance (Morgans) rather than physical distance (base pairs or micrometers). Accordingly, we devise a model in which interference is related directly to genetic distance. Its central feature is that recombinational intermediates (C's) have two fates--they can be resolved with crossing over (Cx) or without (Co). We suppose that C's are distributed at random with respect to each other (no interference); interference results from constraints on the resolution of C's. The basic constraint is that each pair of neighboring Cx's must have between them a certain number of Co's. The required number of intervening Co's for a given organism or chromosome is estimated from the fraction of gene conversions that are unaccompanied by crossover of flanking markers. The predictions of the model are compared with data from Drosophila and Neurospora. PMID- 8454210 TI - Statistical tests of neutrality of mutations. AB - Mutations in the genealogy of the sequences in a random sample from a population can be classified as external and internal. External mutations are mutations that occurred in the external branches and internal mutations are mutations that occurred in the internal branches of the genealogy. Under the assumption of selective neutrality, the expected number of external mutations is equal to theta = 4Ne mu, where Ne is the effective population size and mu is the rate of mutation per gene per generation. Interestingly, this expectation is independent of the sample size. The number of external mutations is likely to deviate from its neutral expectation when there is selection while the number of internal mutations is less affected by the presence of selection. Statistical properties of the numbers of external mutations and of internal mutations are studied and their relationships to two commonly used estimates of theta are derived. From these properties, several new statistical tests based on a random sample of DNA sequences from the population are developed for testing the hypothesis that all mutations at a locus are neutral. PMID- 8454211 TI - Spatial and space-time correlations in systems of subpopulations with genetic drift and migration. AB - The geographic distribution of genetic variation is an important theoretical and experimental component of population genetics. Previous characterizations of genetic structure of populations have used measures of spatial variance and spatial correlations. Yet a full understanding of the causes and consequences of spatial structure requires complete characterization of the underlying space-time system. This paper examines important interactions between processes and spatial structure in systems of subpopulations with migration and drift, by analyzing correlations of gene frequencies over space and time. We develop methods for studying important features of the complete set of space-time correlations of gene frequencies for the first time in population genetics. These methods also provide a new alternative for studying the purely spatial correlations and the variance, for models with general spatial dimensionalities and migration patterns. These results are obtained by employing theorems, previously unused in population genetics, for space-time autoregressive (STAR) stochastic spatial time series. We include results on systems with subpopulation interactions that have time delay lags (temporal orders) greater than one. We use the space-time correlation structure to develop novel estimators for migration rates that are based on space-time data (samples collected over space and time) rather than on purely spatial data, for real systems. We examine the space-time and spatial correlations for some specific stepping stone migration models. One focus is on the effects of anisotropic migration rates. Partial space-time correlation coefficients can be used for identifying migration patterns. Using STAR models, the spatial, space-time, and partial space-time correlations together provide a framework with an unprecedented level of detail for characterizing, predicting and contrasting space-time theoretical distributions of gene frequencies, and for identifying features such as the pattern of migration and estimating migration rates in experimental studies of genetic variation over space and time. PMID- 8454212 TI - Mutation models and quantitative genetic variation. AB - Analyses of evolution and maintenance of quantitative genetic variation depend on the mutation models assumed. Currently two polygenic mutation models have been used in theoretical analyses. One is the random walk mutation model and the other is the house-of-cards mutation model. Although in the short term the two models give similar results for the evolution of neutral genetic variation within and between populations, the predictions of the changes of the variation are qualitatively different in the long term. In this paper a more general mutation model, called the regression mutation model, is proposed to bridge the gap of the two models. The model regards the regression coefficient, gamma, of the effect of an allele after mutation on the effect of the allele before mutation as a parameter. When gamma = 1 or 0, the model becomes the random walk model or the house-of-cards model, respectively. The additive genetic variances within and between populations are formulated for this mutation model, and some insights are gained by looking at the changes of the genetic variances as gamma changes. The effects of gamma on the statistical test of selection for quantitative characters during macroevolution are also discussed. The results suggest that the random walk mutation model should not be interpreted as a null hypothesis of neutrality for testing against alternative hypotheses of selection during macroevolution because it can potentially allocate too much variation for the change of population means under neutrality. PMID- 8454213 TI - Allele frequencies at microsatellite loci: the stepwise mutation model revisited. AB - We summarize available data on the frequencies of alleles at microsatellite loci in human populations and compare observed distributions of allele frequencies to those generated by a simulation of the stepwise mutation model. We show that observed frequency distributions at 108 loci are consistent with the results of the model under the assumption that mutations cause an increase or decrease in repeat number by one and under the condition that the product Nu, where N is the effective population size and u is the mutation rate, is larger than one. We show that the variance of the distribution of allele sizes is a useful estimator of Nu and performs much better than previously suggested estimators for the stepwise mutation model. In the data, there is no correlation between the mean and variance in allele size at a locus or between the number of alleles and mean allele size, which suggests that the mutation rate at these loci is independent of allele size. PMID- 8454215 TI - [Detection of psychosocial dysfunction in ob-gyn patients]. AB - The human behavior and its social determinants are critical variables for understanding the etiology, treatment, and prevention of many disorders previously attributed to biological substrates. Among the many categories of human behavior to receive special attention from health researchers and practitioners are life events, coping responses and emotional state. The relation between these categories constituted a particular field of investigation. This relationship rather than forcing to focus on disease, distress, disability, and other failures in human functioning, permits to address health, abilities, resources, and other positive aspects of human functioning. On the other hand, the re-organization of health services considers interdisciplinary work as an objective, as it is necessary to care for the patient in an integral manner, with the consequent benefit of a more efficient service. In addition it is known that patients with psychosocial dysfunctions who use general practice care facilities overutilize these services in an unnecessary manner. With this in mind it is clear that is necessary to balance the service's cost-benefit for a more efficient clinical attention. In this paper we present the results of the categories mentioned above: life events, coping responses and its relationship with emotional state in a representative sample of 399 female patients who in 1986 received services at the National Institute of Perinatology-INPer-. Of these patients, 297 were obstetrical patients -OBS- and 102 gynaecological ones -GINE-. All patients answered these instruments: General Health Questionnaire -GHQ-7 of 30 items, a subscale of Health and Daily Living for Coping Responses and Life Events Scale.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454214 TI - [Correlation between estradiol concentrations and follicular measurements vs. oocyte maturity in three different ovarian stimulation schedules]. AB - The responses to different ovarian stimulation schedules were studied in women which underwent in programs of assisted fertilization. The follicular development and seric estradiol with the number and quality of the retrieved oocytes. Were correlated 49 patients and divided in 3 groups according to ovarian stimulation schedule were analyzed. The stimulation was followed day by day with seric estradiol and ultrasound follicular measurement. With the three schedules were retrieved 205 oocytes, being mature 179, immature 9 and 17 atretic, there was no significant difference between the different schedules. PMID- 8454216 TI - [Molecular systems in cellular interactions. II: Embryonal implantation in mammals]. AB - In the present paper we consider the molecular mechanisms for cell recognition and cell adhesion on embryo implantation in mammals. In mammalian embryo implantation, the cellular interactions are complex, because several kinds of cells are involved: embryo trophoblast cells interact with several uterine cells and their respective extracellular matrices, participating lactosaminoglycans, integrins, cadherins and galactosyl transferases. PMID- 8454217 TI - [Use of antibiotics in pregnancy. I]. AB - The use of antibiotics during pregnancy have particularly risk, choosing an antibiotic requires consideration of the effects on both the mother and the unborn child. Some antimicrobial agents are safe for use throughout pregnancy, while other are completely contraindicated. Pregnant women need treatment for serious infections, in this cases antibiotics must be used nevertheless the adverse effects of the antimicrobial agent, we must choose the antibiotic with more antimicrobial activity and less risk for the mother and the fetus. PMID- 8454218 TI - [Spontaneous pregnancy, independent of treatment, in sterile couples]. AB - The spontaneous pregnancy independent of treatment in sterility is a frequently observed event in this group of couples. The spontaneous pregnancy appears up to 61% of women with antecedents of sterility and in selected populations of healthy women; a third of them experience, once in their lives a subfertility episode. The characterization of this event in a population with sterility, will help to define the capacity of different diagnostic methods, as well as therapeutic methods in terms of efficacy. The objective of this study was to identify women with diagnosis of sterility and spontaneous pregnancy; to describe the main characteristics: clinical, of laboratory, of gabinet, and to discuss some implications of biological variability useful in the interpretation of these tests. One hundred and eleven patients with sterility and spontaneous pregnancy, in a descriptive and retrospective design, were analyzed. Operational definitions for the main factors related with sterility, were used, as tuboperitoneal, endocrine-ovarian, cervico-vaginal and masculine. The pregnant patients related to any type of treatment, were excluded. Two study groups were established: Group I (n-46) and Group II (n = 65) with primary sterility and secondary sterility, respectively. Average age for both groups was similar (mean = 29 years old). The time of sterility was 46.52 and 43.52 months, for Group I and II, respectively. The time of pregnancy from the point zero (admission), was, in average 6.21 and 4.9 months for Group I and II. The following factors were identified as abnormal: endocrine-ovarian 28.60 by menstrual pattern, progesterone and endometrial biopsy: tuboperitoneal 12.67% by hysterosalpingography and laparoscopy; masculine 12.67 by direct spermatobioscopy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454219 TI - [Liver diseases in pregnancy]. AB - An analysis is made of the hepatopathies characteristic of pregnancy according to the latest research and from experience of the Pathology Department of the Hospital Central of San Luis Potosi. Such entities are the fatty liver, the hyperemesis gravidarum, the preeclampsia and eclampsia and the cholestasis of pregnancy. It is estimated that the eclamptic state is capable of showing clinical, structural and laboratory manifestations which vary absolutely and which bring us to consider as dependent upon the fatty liver, the HELLP syndrome and some cases of cholestasis. Also, cholestasis of pregnancy, determined genetically, must be distinguished from that which is associated with eclampsia or determined by drugs or other causes. Similarly, hyperemesis gravidarum may be primary, although rarely so, or be due to neurological causes; it is also capable of causing slight liver dysfunction. Finally, the above-mentioned ailments are correlated within the classic physiopathological grid of jaundice. PMID- 8454220 TI - [The combined colposcopic index as a diagnostic method in human papillomavirus infection and cervical intraepithelial neoplasia]. AB - This is a prospective, comparative study of 142 patients of combined colposcopic index according to Reid's criterium and the index used at the Clinics of Colposcopy, Gyn-Ob Hospital "Luis Castelazo Ayala", IMSS. Seventy two patients were studied with the Hospital Index, and 70 with the CCI. This constituted by neatness of peripheral edges, the color, characteristics of vessels and iodine tinction; a score of 0, 1, 2 was given, the sum of which gave a final qualification, and it was traspolated to a colposcopic diagnosis. The CCI correlated with the histological diagnosis in 64 patients (91.42%); while for the Hospital Index it was in 61 cases (84.7%). The indexes showed a good sensitivity (0.95), a high positive predictive value (0.95 vs 0.88), and adequate accuracy (0.91 vs 0.84), as well as a good prevalence (0.90 vs 0.85). It is concluded that the CCI is reliable for the colposcopic diagnosis of human papillomavirus and for CIN. PMID- 8454221 TI - [Management of severe pre-eclampsia/eclampsia. Comparison between nifedipine and hydralazine as antihypertensive agents]. AB - The objective was to compare the fetal and maternal effects between parenteral hydralazine and sublingual nifedipine used like antihypertensive drugs in the management of severe preeclampsia. Study design was prospective, comparative, longitudinal, randomized clinical trial. It was carried out at Centro Medico Nacional IMSS Torreon, Coah. Gynecology and Obstetrics Department. The patients were women in the last trimester of pregnancy with severe preeclampsia were randomized to receive parenteral hydralazine or sublingual nifedipine as antihypertensive drugs. The only difference observed in this study was the Apgar of neonates whose mothers received hydralazine, that was significatively lesser than the Apgar of neonates whose mothers received nifedipine. Both medicaments are a good alternative as antihypertensive drugs in severe preeclampsia. Neonates whose mothers received Nifedipine had a higher Apgar. PMID- 8454222 TI - [Perception of reproductive risk factors]. AB - The objective of this study was to identify risk perception on several factors related to reproductive health, with the goal of implementing an educational intervention based on detected needs. 405 women between 12 and 44 years were interviewed at home. 62.2% perceived the risk of pregnancy at 17 years and younger; 78.8% the risk of pregnancy at 35 years and older; 76.6% the risk of parity of 5 and higher; and 55.1% the risk of birth interval of 2 years and less. 60.5% recognized family history of birth defects, 80.2% age 35 years and older, and 84.4% rubella during pregnancy, as risk factors for newborns with congenital malformations. 27.7% identified history of a low birth weight and 61.0% birth interval of 1 year and less, as risk factors for low birth weight. The majority perceived the risk of tobacco, alcohol and drugs consumption during pregnancy, diseases with no treatment and deficient nutrition. There was an inconsistent influence of social and obstetric variables on risk perception. No linear correlation was detected. Health educators should recognize differences on knowledge and behavior of future receptors before an educational intervention starts. PMID- 8454224 TI - Decreased susceptibility of liver mitochondria from diabetic rats to oxidative damage and associated increase in alpha-tocopherol. AB - The susceptibility of mitochondria from liver and kidney of diabetic and normal rats to in vitro oxidative damage was assessed. Mitochondria were isolated from diabetic rats 4 weeks after streptozotocin injection and from age-matched, normal rats. Liver mitochondria from diabetic rats were less susceptible to oxidative damage (induced by Fe3+/adenosine 5'-diphosphate (ADP) xanthine/xanthine oxidase), as assessed by the formation of thiobarbituric acid reacting substances (TBARS) and sulfhydryl loss, than were mitochondria from normal rats. The decreased susceptibility of liver mitochondria from diabetic rats to oxidative damage correlated with a sevenfold increase in mitochondrial alpha-tocopherol levels. Activities of the antioxidant enzymes, glutathione reductase, glutathione peroxidase, and superoxide dismutase, were lower in liver mitochondria from diabetic compared to normal rats. Manipulation of dietary alpha-tocopherol, to counteract the increased intake of alpha-tocopherol due to diabetes-associated polyphagia, failed to lower liver mitochondrial alpha-tocopherol to the levels found in normal rats. Mitochondria from kidney of diabetic rats were equally as susceptible to in vitro oxidative damage as kidney mitochondria from normal rats. They had increased levels of superoxide dismutase and glutathione peroxidase but identical levels of alpha-tocopherol compared to mitochondria from normal rats. Dietary manipulation of alpha-tocopherol had no effect on kidney mitochondrial levels of the nutrient. PMID- 8454223 TI - Biotransformation of para-aminobenzoic acid and salicylic acid by PMN. AB - Para-aminobenzoic acid (PABA) is an essential cofactor for the production of folic acid in bacteria and has mild anti-inflammatory activity. We have recently reported that salicylic acid and benzoic acid are oxidized by stimulated granulocytes Polymorphonuclear Neutrophils (PMN). The oxidation of salicylate appears mediated by a potent oxygen metabolite generated during the respiratory burst which is dependent primarily on superoxide (O2-) for its production. These background studies with the salicylate group of drugs suggested that PABA might be similarly metabolized by PMN. In these studies, we demonstrate that PABA is metabolized by stimulated PMN. However, in contrast to the biochemical mechanism involved in the metabolism of salicylate, our scavenger studies indicate that PABA is metabolized primarily by the myeloperoxidase pathway. Our results may explain the mild anti-inflammatory actions of the drug and suggest that the degradation of PABA by PMN at an inflammatory site may limit the availability of PABA for bacterial growth. PMID- 8454225 TI - Probucol as an antioxidant and antiatherogenic drug. AB - Recently, interest has increased in the hypothesis that low-density lipoprotein (LDL) modified by oxidation may lead to the initiation and to the development of atherosclerosis. In vitro studies of cellular interactions with LDL have revealed that various cells, including endothelial cells and smooth muscle cells, can oxidize LDL. The biochemical changes in LDL may further enhance its atherogenic potential. In addition to these in vitro studies, there is in vivo evidence for oxidized LDL in atherosclerotic lesions and for circulating antibodies against oxidized LDL. Probucol, 4,4'-(isopropylidenedithio)bis(2,6-di-tert-butylphenol), is a widely used cholesterol-lowering drug. Recently, there has been accumulating evidence for other mechanisms of probucol's antiatherogenic effects apart from cholesterol-lowering action. Attention has especially focused on probucol's antioxidant action in the mechanism of antiatherogenesis. In the present article, we will summarize the antiatherogenic and antioxidant actions of probucol. PMID- 8454226 TI - Oxygen radicals and the control of ovarian corpus luteum function. AB - The superoxide radical (SOR) and other reactive oxygen species form in cells during the course of respiration as well as in response to various stimuli. Although well known for their damaging effects, these agents can also work beneficially to control cell function. The present review examines the evidence that oxygen radicals and H2O2 may regulate steroid hormone biosynthesis in the ovarian corpus luteum. Recent findings indicate that luteal cells can employ reactive oxygen species at specific sites in controlling the production of progesterone over the course of the reproductive cycle and in inhibiting its synthesis during regression at the end of the cycle. These studies indicate that oxygen radicals and related compounds may function as intracellular regulators of steroidogenesis in the corpus luteum. PMID- 8454227 TI - Dietary versus cellular zinc: the antioxidant paradox. PMID- 8454228 TI - [Genetic polymorphism in human drug metabolism]. AB - During the last decade, the influences of genetic factors on individual drug metabolizing capacity in humans have been characterized in fairly great detail at the molecular level. Debrisoquine/sparteine and mephenytoin polymorphisms are now known to be derived from defects in the human liver of specific forms of microsomal CYP (P450 or previously termed cytochrome P-450), CYP2D6 and CYP2C9 (2C18), respectively. In these polymorphisms, clear ethnic differences are observed in the incidence of poor metabolizers (PM). Although debrisoquine PM is detected in high incidence (5-10%) in Caucasians, little was found in Japanese. In contrast, mephenytoin PM is detected in higher percentages in Japanese (15 25%) than in Caucasians (3-7%). In this mini-review, current understanding of the molecular mechanisms of both types of polymorphism and structural relationships of CYP2D6 and CYP2C9 substrates are shown. Relationships between specific phenotypes and cancer risks or disease are also discussed. PMID- 8454229 TI - [Effects of intravenous administration of nasaruplase, a plasminogen pro activator, on left ventricular function and systemic hemodynamics in a canine model of acute myocardial infarction]. AB - The thrombolytic effects and changes in left ventricular function after intravenous administration of nasaruplase were examined in a canine thrombus model of acute myocardial infarction. When 8 U/kg/min of nasaruplase was intravenously administered after 30 min of coronary arterial occlusion, coronary recanalization was achieved in 78.6% (11/14) of the animals with little change in plasma fibrinogen concentration. There was no further decrease in cardiac output, left ventricular ejection fraction or regional wall motion immediately after reperfusion, compared with 30 min after coronary arterial occlusion. However, all these parameters returned to pre-occlusion levels one week after reperfusion. Nasaruplase markedly reduced infarct size as well as cardiac hypertrophy following coronary arterial occlusion, demonstrating suppression of the development of ischemic myocardial damage. These results indicate that coronary thrombolytic therapy with intravenous administration of nasaruplase is useful for the treatment of acute myocardial infarction. PMID- 8454230 TI - [Effect of recombinant human superoxide dismutase (r-h-SOD) on reperfusion induced irreversible arrhythmia in anesthetized rats]. AB - Using anesthetized rats, we performed a dose-response study of the ability of r-h SOD to reduce the mortality caused by reperfusion-induced irreversible arrhythmia. The hearts were subjected to regional ischemia by the occlusion of the left coronary artery for 4 min followed by reperfusion for 7 min. First, the relation between the anti-arrhythmic effect of r-h-SOD and the size of the ischemic zone was examined. The protective effect of r-h-SOD was easily detected in rats with an ischemic zone size of 40-55% of the total heart weight, but not in rats with other zone sizes. Intravenous infusion of r-h-SOD at rates of 430 to 130,000 U/kg/min beginning 1 min after regional ischemia significantly reduced the mortality after reperfusion. R-h-SOD at the doses used did not affect the blood pressure, heart rate or arrhythmia during the ischemic period. R-h-SOD at rates of 130 to 130,000 U/kg/min was intravenously infused into anesthetized rats, and its plasma level was measured at 3 min after the beginning of the infusion. The plasma level of r-h-SOD increased dose-dependently (8.5 to 6,600 U/ml). In conclusion, r-h-SOD reduced mortality after reperfusion over a wide range of doses and its effective plasma level was estimated to be 28 to 6,600 U/ml in this model. PMID- 8454231 TI - High pressure water injection injuries of the foot: a report of two cases. AB - Few cases of high pressure water injection injuries of the foot have been reported. These cases suggest that only minimal soft tissue destruction results and that, with conservative or limited surgical management, full recovery should be expected. This is a report of two cases of this "benign variant" of high pressure water injection injury that resulted in toe amputations. PMID- 8454232 TI - Metatarsal shaft fracture after first metatarsophalangeal joint fusion: a complication of Steinmann pin fixation. AB - First metatarsophalangeal joint fusion is a successful procedure for the treatment of rheumatoid forefoot problems, severe osteoarthritis of that joint, and failed first ray surgeries. We have identified three patients with fracture of the first metatarsal after fusion with Steinmann pins. Penetration of the plantar and/or plantar medial cortex of these pins should be avoided. If penetration occurs, we recommend casting after pin removal. PMID- 8454233 TI - Circumferential toenail. AB - Congenital deformities occur in approximately 1% of all live births. The exact incidence of congenital foot deformities is unknown. The presence of a circumferential nail of the toe is a very rare deformity. In our review of the literature, we have encountered only two previously reported cases of circumferential toenails. In these cases the patients were siblings and also had circumferential fingernails. This report describes circumferential toenails without other hand or other congenital deformities. PMID- 8454234 TI - Kinematics of the ankle: a hinged axis model. PMID- 8454235 TI - Unilateral external fixation for severe pilon fractures. AB - Twenty-one patients with severe tibial plafond fractures were treated by unilateral large screw external fixation. In 15 patients, this was combined with limited internal fixation. The fractures were classified according to the methods of Ovadia and Beals. There were nine type III, four type IV, and eight type V fractures, and according to the methods of Ruedi and Allgower, nine type II and 12 type III fractures. Seven fractures were open. In five fractures, no attempt was made at articular reconstruction due to severe comminution. Four of these fractures required ankle arthrodeses and one type IIIB fracture received a late amputation. All other fractures healed. There were no cases of wound infection, skin slough, or osteomyelitis. Large screw external fixation in the talus and calcaneus was not associated with significant early or late complications. The less extensive tissue dissection in an area prone to wound complications may account for the low rates of infections, wound complications, and nonunion. PMID- 8454236 TI - Syme amputation in patients with severe diabetes mellitus. AB - Surgical results and functional outcome of 52 patients treated with Syme amputations for forefoot gangrene between 1986 and 1988 were retrospectively reviewed with reference to the predictive value of posterior tibial artery Doppler examination. Wound healing was correlated with the preoperative status of the posterior tibial artery. Functional outcome was assessed by the ability to wear a prosthesis, ambulatory capabilities, episodes of ulceration, and revision surgery. Follow-up averaged 27 months. Twenty-nine patients had a posterior tibial artery with either a triphasic waveform (N = 23) or a normal pulse (6). Twenty-six (90%) of these achieved a healed wound suitable for prosthetic wear. Twenty-three patients had monophasic flow in the posterior tibial artery. Thirteen (57%) of these achieved a healed wound. Ninety percent of the patients who achieved healed wounds were fit with a prosthesis. Functional level of ambulation was assessed in 20 patients. Eighteen were community level ambulators, 11 could walk three or more blocks, and 16 could climb stairs. Eighteen wore their prosthesis all day. These findings indicate that posterior tibial artery Doppler examination is predictive of healing in the Syme amputation performed on diabetics. Furthermore, diabetics can attain a functional level of ambulation with a Syme amputation. PMID- 8454237 TI - American Orthopaedic Foot and Ankle Society women's shoe survey. AB - Shoes have been implicated as being responsible for the majority of foot deformities and problems that physicians encounter in women. A total of 356 women were studied in this investigation to evaluate trends in women's shoe wear and their effect on the development of foot deformities and pain. The majority of women in this study wore shoes that were too small for their feet, had foot pain and deformity, and had increased shoe size since the age of 20. Few women had their feet measured in over 5 years. The women without foot pain or deformities also wore shoes that were smaller than their feet but to a lesser degree. PMID- 8454238 TI - The role of the plantar first metatarsal first cuneiform ligament in weightbearing on the first metatarsal. AB - Twelve below the knee amputation specimens were examined while a dorsally directed force was applied to the first metatarsal. Seven specimens were tested with serial removal of soft tissues, followed by cutting the plantar first metatarsocuneiform ligament. Five specimens had only the plantar first metatarsocuneiform ligament cut, leaving the other structures intact. In both groups, dorsal displacement of the distal first metatarsal was noted to be more than 5 mm after sectioning of the ligament, with no marked change noted during removal of other soft tissues. This study demonstrates that the plantar first metatarsocuneiform ligament is the major component in the stabilization of the first metatarsal during weightbearing. PMID- 8454239 TI - Influence of metatarsal head displacement on metatarsal pressure distribution after hallux valgus surgery. AB - We reviewed 63 feet after plain subcapital osteotomy for simultaneous correction of hallux valgus and metatarsus primus varus. Results were evaluated clinically and by radiographs and force plate measurements. Eighty-three percent of the patients were satisfied with their surgery. The hallux valgus angle was improved by 9.3 degrees and the intermetatarsal angle by 6 degrees. The osteotomy resulted in a displacement of the metatarsal head in the lateral direction (10 mm) and in the plantar direction (11.3 mm). Normalization of the load distribution on the metatarsal head was achieved in the group with 11 to 15 mm of plantar displacement. Based on our results, we recommend plain subcapital osteotomy for hallux valgus deformities with moderate metatarsus primus varus. After correction of the intermetatarsal angle and sufficient plantar displacement a physiological distribution of load on the metatarsal head can be expected. PMID- 8454240 TI - The Chevron bunionectomy: a trigonometric analysis to predict correction. AB - A trigonometric analysis was developed in an attempt to predict the postoperative hallux valgus angles and intermetatarsal angles after Chevron bunionectomy. This analysis was used in 20 feet to predict postoperative angles, and these predicted values were compared with actual measured roentgenographic values. The postoperative intermetatarsal angles were evaluated to determine their correction to postoperative hallux valgus angles of 20 degrees or less. Using the trigonometric analysis, the postoperative intermetatarsal angles were highly predictable, but the hallux valgus angle could not be reliably predicted for individual patients. The intermetatarsal angle obtained at surgery, however, was indicative of the final hallux valgus angle: 75% of feet with intermetatarsal angles of more than 11 degrees had postoperative hallux valgus angles of more than 20 degrees. Thus, when an intermetatarsal angle of 11 degrees or less can be obtained surgically, the hallux valgus angle can be corrected to 20 degrees or less in most patients. PMID- 8454241 TI - Changes in gait and maximum ankle torque in patients with ankle arthritis. AB - Findings from quantitative gait analysis and maximum ankle torque were used to assess the walking pattern of patients with ankle arthritis and to correlate the changes of gait parameters and muscle strength with severity of arthritis. Gait analysis and the isokinetic maximum ankle torque test were performed in 20 patients with first to fourth degree traumatic ankle arthritis. Six patients without evidence of traumatic arthritis were used as controls. Isokinetic maximum ankle plantarflexion and dorsiflexion torques were determined with Cybex instrumentation. Force plate and foot switch data were gathered during level walking. Maximum ankle plantarflexion and dorsiflexion torques were diminished in the injured ankles. Velocity, stride length, and cadence were decreased in arthritic patients compared with controls. The arthritic limbs had shorter single limb stance and longer double stance during free and fast walking speeds compared with the controls' affected ankles. The patterns of ground reaction forces were similar in the injured and uninvolved limbs as well as the control subjects, except the magnitude of vertical forces during push-off were reduced in arthritic ankles. The gait parameters and muscle strength deteriorated as the arthritis became severe, but they showed significant changes only when the patients had third or fourth degree arthritis. PMID- 8454242 TI - [The interrelationships between dental parameters and electronic axiographic findings. A study on subjects with nonphysiological incisor relations]. AB - The purpose of the present study was to discern possible relationships between dental parameters and the horizontal inclination of the condyle path. Two test groups of orthodontically untreated individuals with non-physiological incisor relationships, one group with enlarged and the other with reverse overjet, were selected for the study. An opto-electronic apparatus was employed to measure the horizontal inclination of the condyle path. The dental parameters were set by clinical examination and by measuring plaster casts. Both groups exhibited significant distribution deviations in the inclination of the condyle path and in the following parameters: "occlusal contacts of the front teeth during protrusion", "overbite", "resulting overjet", and "sagittal and vertical distance of the incisal edge of the lower incisors to the zero point of the upper incisors". Statistically no correlation between the dental parameters and the inclination of the condyle path was discerned. The influence of muscular guidance is in large measure the determining factor for the large variations in the TMJ registrations, and especially in their quantitative evaluation. The results were the same even when tracings were repeated a number of times with the same patient. PMID- 8454243 TI - [Dentoalveolar adaptation in vertical jaw-base discrepancies]. AB - The aim of this study was to determine the constancy and the extent of the dentoalveolar adaptation in subjects with disharmonious vertical jaw base relationships. Lateral head films in centric occlusion of 66 untreated adults were analysed. The subjects were divided in three facial type groups on the basis of the mandibular base angle (ML/NSL): hypodivergent (n = 23), normodivergent (n = 18), and hyperdivergent (n = 25). The relationships between maxillary and mandibular anterior and posterior dentoalveolar heights and vertical jaw base relationship were ascertained. The study revealed the following: an increase in vertical jaw base angle resulted in 1. an increase in maxillary and mandibular anterior and posterior dentoalveolar heights, 2. a larger increase in maxillary than in mandibular dentoalveolar height, and, 3. a larger increase in anterior than posterior dentoalveolar height. The study divulged the presence of dentoalveolar adaptation in subjects with a divergent vertical jaw base relationship. This adaptation, however, was inconsistent and in some cases incomplete. PMID- 8454244 TI - [Video-supported dynamic B-mode sonography of tongue function during swallowing]. AB - A dynamic B-mode ultrasound technique supported by video recording was employed on 51 patients between the ages of six and 45 years for the purpose of imaging the tongue at rest and in motion during swallowing. All patients either in their case histories or at clinical examination demonstrated orofacial dysfunction of the tongue or an abnormal oral phase during swallowing. The ultrasound sequences of a 5 MHz sector scanner (100 degrees, 30 images/sec) were videotaped for the purpose of analyzing the sagittal and vertical movement components during swallowing. The sagittal sector scan revealed a visceral swallowing pattern in 21 patients. Noticeably often patients with an Angle class III malocclusion also displayed an abnormal swallowing pattern. Ultrasound scanning in the coronal and sagittal plane is a noninvasive imaging technique free of the biological risks associated with radiation. The dynamic ultrasound technique may be employed for early detection and diagnosis of tongue discoordinations and is especially to be recommended for the objective imaging and identification of tongue thrust in orthodontic patients. PMID- 8454245 TI - [Temporomandibular joint function after orthognathic surgery--the individual factors]. AB - Case studies presented in the literature present evidence that individual factors may influence mandibular mobility unfavorably after mandibular advancement osteotomies. These factors are, respectively: high preoperative dysfunction index, preoperative articular pain in movement, preoperative reciprocal clicking, advanced patient age, and significant overjet reduction. This study identifies these individual factors, which can influence postoperative functional condition, and documents conclusively the importance of individual, function oriented preoperative planning in orthognathic surgery. Taken together these factors indicate that the adaptation ability of the effected tissue should be given greater attention in planning the operation. PMID- 8454246 TI - [The bonding strength of silane-coated metal brackets with different adhesives]. AB - The aim of this study was to test under thermo stress the effect of various adhesives on the bonding strength of brackets with a new retention mechanism in comparison to brackets with a conventional retentive basis. In the test 17 different adhesives and metal brackets with two different retention mechanisms were used. One group of metal brackets was coated by means of the Kulzer silane coating procedure and the other had a mesh basis. The latter served as the control group. Both were held in place by adhesives and their bonding strength tested. The following conclusions were drawn: 1. Both of the bracket types demonstrated the highest bonding strength with the mixed composites (paste/paste). 2. The silane coated bracket bases demonstrated altogether higher bonding strength than the mesh brackets, but the difference with the light-cured and the epoxy-adhesives was only statistically significant. PMID- 8454247 TI - [The digital reprocessing of under- and overexposed x-ray films with a personal computer]. AB - An image processing work station for digitalizing and interactively manipulating under- and overexposed X-rays was set up by adding modules to an IBM compatible personal computer. Overexposed X-rays can be qualitatively enhanced by means of controlled manipulation of contrast and brightness and by means of the use of various digital filtering techniques. With underexposed X-rays an equalized grey scale can be achieved by means of regulating contrast and brightness. Digital filtering is not required. To assure a high degree of anatomical detail (periodontal ligament) in the digitalized image a maximum pixel of 0.1 mm was defined as a qualitative norm. Since in every digitalization process resolution is diminished, it proved best to select for interactive manipulation out of the total image only the section of interest. PMID- 8454248 TI - [New ACE inhibitors on the testing block. Blood pressure control and arteriosclerosis prevention with Benazepril. Report from the Benazepril Symposium following the 41st Annual Scientific Session of the American College of Cardiology. Dallas, Texas, 12-16 April 1992]. PMID- 8454249 TI - [Therapy of atrial fibrillation with class III anti-arrhythmia agents]. AB - Medical treatment of atrial fibrillation has been carried out most frequently with digoxin, quinidine, propafenone or flecainide. In spite of unequivocal efficacy, the use of class I antiarrhythmic agents is the subject of considerable controversy. In addition to increased mortality in patients with ventricular arrhythmias after myocardial infarction, proarrhythmic effects with flecainide have also been described in patients with supraventricular arrhythmias. A meta analysis of long-term treatment of atrial fibrillation with quinidine disclosed that the mortality in those treated with quinidine at 2.9% was significantly higher than those receiving placebo at 0.8%. In consideration of the prevailing uncertainty with the use of class I antiarrhythmic agents, class III antiarrhythmic drugs such as sotalol and amiodarone have been administered for supraventricular arrhythmias with increasing frequency. Treatment of atrial fibrillation with sotalol Sotalol is a noncardioselective beta-adrenergic receptor blocker with antiarrhythmic properties of class III. This drug prolongs the duration of the action potential and the refractory periods in atrial and ventricular myocardium and slows the AV-conduction as well as the sinus node rate. On oral administration, there is good resorption and a half-time of seven to 18 hours. The effective oral dose varies between 80 and 320 mg/12 hours. For conversion of acute supraventricular arrhythmias, an i.v. bolus of 0.5 to 1.5 mg/kg has been used. The results of clinical studies with sotalol in the treatment of atrial fibrillation are shown in Table 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454250 TI - Anticoagulation and atrial fibrillation. AB - The decision to anticoagulate patients with atrial fibrillation (AF) involves weighting the risk of an embolic event without therapy versus the risk of a hemorrhagic event on therapy. Improved methods of monitoring anticoagulation with the International Normalized Ratio (INR), and recent evidence of the efficacy and safety of low-dose warfarin (INR range 2.0 to 3.0) have clarified the role of anticoagulation in AF. Over the past four years, five large prospective randomized trials in patients with nonvalvular atrial fibrillation (NVAF) have reported substantial reductions in stroke in patients treated with low-dose warfarin therapy. The results of these trials, combined with previous studies, suggest that anticoagulation is the treatment of choice for patients with atrial fibrillation associated with rheumatic valvular disease, prosthetic valve disease, and now NVAF. Although the results of the prospective atrial fibrillation trials are very consistent in regard to the efficacy and safety of anticoagulation, there continues to be uncertainty regarding which subgroups of patients are at highest risk for embolic events. Subgroups that appear to be at high risk include patients with hypertension, previous embolic events, structural heart disease (enlarged left atrial size, previous myocardial infarction, left ventricular dysfunction), and older age. Young patients with no evidence of structural heart disease or hypertension (lone atrial fibrillation) have a low embolic rate and do not warrant anticoagulation. Recent studies suggest that there is little difference in the risk of stroke in patients with paroxysmal or chronic AF, therefore this factor should not have a major impact on therapeutic decisions. Anticoagulation is also recommended for patients undergoing elective cardioversion (recent onset of atrial fibrillation greater than two days in duration), and patients with atrial fibrillation and hyperthyroidism because of studies suggesting a higher rate of embolism if these patients are not anticoagulated. The role of aspirin in AF is less clear as only two of the five prospective trials randomized patients to aspirin therapy and only one documented aspirin benefit. Therefore, aspirin appears to offer less benefit but is a satisfactory alternative to warfarin therapy. Aspirin is currently recommend for patients who are poor candidates for anticoagulation or individuals with AF who are considered to be at low risk for stroke. PMID- 8454252 TI - Surgical treatment of atrial fibrillation. AB - Recently, two new rationale for surgical treatment of atrial fibrillation have been developed which have been used, initially, primarily in patients with lone atrial fibrillation. We performed the "corridor" operation in eleven patients with paroxysmal or chronic atrial fibrillation. Postoperatively, eight patients had normal sinus rhythm, one had a junctional rhythm, one patient had atrial tachycardia and one had intermittent atrial flutter/fibrillation with sinus bradycardia. During a mean observation period of 18 months, recurrent intermittent atrial fibrillation occurred in two patients. Another study reported the results of 20 patients with paroxysmal atrial fibrillation. During a mean observation period of 32 +/- 14 months, one patient had a brief episode of atrial fibrillation and three patients had atrial tachycardia amenable to antiarrhythmic drug treatment. The "Maze" operation was performed in 22 patients with resistant lone atrial fibrillation or atrial flutter. Postoperatively, eight patients had atrial flutter/fibrillation which, however, could be controlled in three with antiarrhythmic drug treatment. In all patients serious symptoms were improved but adjunctive measures and/or antiarrhythmic drugs were required frequently. There was no intraoperative mortality with either the corridor or the Maze operation but substantial postoperative morbidity was observed which, currently, exceeds that of the natural history or other ablative techniques. PMID- 8454251 TI - Surgical therapy for atrial fibrillation. AB - Atrial fibrillation is the most common sustained rhythm other than sinus rhythm encountered in clinical practice. There are three detrimental sequelae to the rhythm of atrial fibrillation, although the relative magnitude of the detriment varies from patient to patient. These include the sensation of the irregular heart beat, the hemodynamic compromise that is associated with the loss of atrial transport function, and the third is the risk of thromboembolism. Twelve years of experimental and clinical investigation have resulted in the development of a surgical procedure to cure patients with both paroxysmal and chronic atrial fibrillation, as well as atrial flutter. The operation is successful in restoring all patients to sinus rhythm, restoring atrial transport function, and in preventing the recurrence of atrial fibrillation. This procedure is becoming the treatment of choice in patients with drug-refractory, symptomatic atrial fibrillation. PMID- 8454253 TI - [Atrial fibrillation in Wolff-Parkinson-White syndrome. Development and therapy]. AB - In patients with Wolff-Parkinson-White syndrome the accessory pathway may participate in various tachyarrhythmias thereby influencing symptoms and prognosis. Atrial fibrillation occurs in 10 to 32% of patients and may have life threatening consequences by precipitating ventricular fibrillation in patients with rapid conduction due to an accessory pathway with short anterograde refractory period (< 250 ms). Pathogenesis of atrial fibrillation in the WPW syndrome and therapeutic options are reviewed in this presentation. Spontaneous degeneration of atrioventricular reentrant tachycardia has been reported to represent the most frequent mode of initiation of atrial fibrillation during electrophysiologic study (up to 64% of episodes). Hemodynamic changes during tachycardia may lead to increased sympathetic tone, hypoxemia or increased tension of the atrial wall, thus, triggering atrial fibrillation. Induction of reentrant tachycardia during electrophysiologic study also has shown to be strongly correlated to its clinical prevalence and is inducible in up to 77% of patients with atrial fibrillation. The pathogenesis and high incidence of atrial fibrillation in patients with WPW syndrome is related to presence and functional properties of the accessory pathway. After surgical excision or catheter ablation more than 90% of patients are free of this arrhythmia. Anterograde conduction properties of the pathway appear to be more important than retrograde properties. High incidence of atrial fibrillation is related to short anterograde refractory periods, and of note, this arrhythmia is rare (3%) in patients with concealed pathways. With intracardiac recordings, Jackman et al. could demonstrate atrial fibrillation due to micro-reentry originating in accessory pathway networks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454254 TI - Modern concepts of atrial fibrillation. AB - Atrial fibrillation (AF) is recognized as a common cardiac arrhythmia associated with significant morbidity and mortality. The mechanism of AF depends on the type, paroxysmal (P) AF is usually secondary to autonomic imbalance and chronic (C) AF is typically secondary to cardiovascular dysfunction. There is significant overlap as most patients with PAF will eventually develop CAF. Therapeutic considerations depend mostly on the clinical situation ranging from emergent electrical therapy for unstable patients to no therapy for asymptomatic patients. Most patients are mildly symptomatic from rapid heart rate (ventricular response) and benefit from drugs designed to create AV block. Anticoagulation is important additional therapy in order to prevent thromboemboli. Reversion of AF and maintenance of sinus rhythm would be the ideal goals of therapy except for the toxicity of available agents. As a result many patients would be best left in AF as the rhythm of choice. PMID- 8454255 TI - Class 1 antiarrhythmic agents for therapy of atrial fibrillation. AB - Atrial fibrillation is most the common sustained arrhythmia seen by the cardiologist. Therapy to prevent this arrhythmia is often prescribed so as to eliminate associated symptoms which include palpitations, fatigue, dizziness and presyncope, shortness of breath, congestive heart failure and emboli, especially those that result in a cerebrovascular accident. Pharmacologic therapy is the only effective therapy for preventing atrial fibrillation and the class 1 antiarrhythmic drugs remain the most frequently used agents. Although each of these agents has been reported to be effective for preventing atrial fibrillation, they are associated with frequent side effects, some of which are potentially serious, especially aggravation of arrhythmia. Prior to treatment the benefit vs risk of these drugs for each patient must be established. PMID- 8454256 TI - Ossifying fibromyxoid tumour of soft parts: immunohistochemical and ultrastructural analysis. AB - Ossifying fibromyxoid tumour of soft parts is a recently described benign neoplasm which usually presents in soft tissue. The histogenesis or pattern of differentiation is a source of controversy. Thirteen cases are reported herein. All arose in adults, principally on the upper trunk or head and neck region. None recurred. All but one tumour showed a shell of lamellar bone, laid down by reactive osteoblasts, at the tumour-host interface. The characteristic laciform, glomoid and fascicular patterns, usually in combination, necessitate differential diagnosis from chondroid, smooth muscle and neural tumours especially. Immunohistochemistry revealed positivity for S-100 protein in 10/12, desmin in 7/10 and smooth muscle actin in 4/8. Ultrastructural examination of four cases revealed prominent intermediate filaments, without myofilamentous organization, and a discontinuous external lamina. Immunoelectronmicroscopy localized desmin positivity to the filamentous meshwork. Differentiation therefore appears to take the form of an incomplete neural and smooth muscle phenotype, without evidence of complete maturation. PMID- 8454257 TI - High incidence of papillary renal cell tumours in patients on chronic haemodialysis. AB - Papillary and nonpapillary renal cell tumours can be differentiated according to their genetic constitution. In this study, their incidence in end stage kidney disease has been investigated histologically. Nonpapillary renal cell carcinoma was observed in 22 cases (51.2%) whereas papillary renal cell tumours were diagnosed in 21 (48.8%) of the 43 patients with end stage kidney disease. The incidence of papillary renal cell tumours in end stage kidney disease is significantly higher (chi 2 = 31.9; P < 0.001) than in the general population (4.8%). Haemodialysis patients with nonpapillary and papillary renal cell tumours did not show significant differences in age, sex or size of tumour. However, patients with papillary renal cell tumours had received longer duration of haemodialysis than patients with nonpapillary renal cell carcinomas. These data suggest that not only different genetic events but also different aetiological factors are involved in the development of the two types of tumour in end stage kidney disease. PMID- 8454258 TI - Expression of the Ig-associated heterodimer (mb-1 and B29) in Hodgkin's disease. AB - Eighty-three cases of Hodgkin's disease were studied immunocytochemically for the presence of the Ig associated heterodimer (mb-1 and B29) which is believed to be a specific pan B-cell marker. These results were compared with those achieved using other B-cell markers against CD19, CD20 and CD22. Although a small number of cases of nodular sclerosis and mixed cellularity subtype showed positivity for CD19, CD20 or CD22, no case showed any reactivity with antibodies against mb-1 or B29. This contrasted markedly with the cases of lymphocyte predominance where all seven cases expressed one or more of the B-cell antigens, with six cases being positive for mb-1. These results confirm previous studies that have suggested lymphocyte-predominance Hodgkin's disease is of B-cell origin and different from the other subtypes. However, they do not provide support for the thesis that these other subtypes may also have a B-cell origin, albeit with a different phenotype to lymphocyte predominance. PMID- 8454259 TI - Detection by in situ hybridization of HIV and c-myc RNA in tumour cells of AIDS related B-cell lymphomas. AB - The incidence of acquired immune deficiency syndrome (AIDS)-related malignant lymphoma has increased since the disease was first described, but its pathogenesis is still not understood. There have been numerous molecular studies addressing the clonality of these proliferations, the presence of Epstein-Barr virus genome in the tumor cells, and rearrangements of the c-myc oncogene. However, very few in situ hybridization studies have been carried out. We analysed 24 cases of high-grade B-cell malignant lymphomas and two cases of polymorphic B-cell proliferation associated with human immunodeficiency virus (HIV) infection. Human immunodeficiency virus ribonucleic acids were detected in some of the tumour cells in 19 of the 24 cases of malignant lymphomas and in both cases of polymorphic B-cell proliferation, with the in situ hybridization technique and using a specific tritiated copy deoxyribonucleic acid probe. With the same technique, c-myc ribonucleic acid was detected in most of the tumour cells from all the 21 cases of malignant lymphomas tested but not in the polymorphic B-cell proliferation. PMID- 8454260 TI - Acquired aganglionosis following surgery for Hirschsprung's disease: a report of five cases during a 33-year experience with pull-through procedures. AB - Acquired Hirschsprung's disease is a rare and controversial form of colonic aganglionosis. Little is known about its aetiology and pathogenesis. We report five cases encountered amongst 173 long-term follow-up patients treated for classical Hirschsprung's disease between 1957 and 1990 at the Red Cross Children's Hospital, Cape Town, and review the current literature. The clinical and pathological findings of the cases have been studied to explore possible aetiological mechanisms. Our cases, like most of those previously reported, developed obstructive symptoms and acquired aganglionosis in pulled-through bowel which had been previously confirmed as ganglionated. Two patients had histological evidence of hyaline fibrosis of blood vessels in the segment of bowel with acquired aganglionosis. Such fibrosis and other features attributable to regional hypoxia were not found in the other three cases. It is suggested that ischaemia with fibrosis may have a pathogenetic role in some, but not all, cases of acquired Hirschsprung's disease. A plea is made for patients developing recurrent symptoms of Hirschsprung's disease, after adequate surgical correction, to be fully studied with repeated sequential biopsies in order to gain a better understanding of the entity. PMID- 8454261 TI - A histological and electronmicroscopic study of intracorneal melanin in benign and malignant melanocytic lesions. AB - Intracorneal melanin is a feature quite frequently encountered in a range of melanocytic lesions, yet has rarely been described in the literature. We examined a variety of melanocytic lesions with increasing degrees of melanocytic atypia for this feature. The distribution and amount of intracorneal melanin is described and it was shown to be entirely within keratinocytes. In general, the amount of intracorneal melanin was related to increasing melanocytic atypia and was typically distributed in a disorderly fashion in malignant lesions. PMID- 8454262 TI - Seminal vesicle amyloidosis: morphological, histochemical and immunohistochemical observations. AB - Subepithelial deposits of amyloid were detected within the seminal vesicles of 13 males from a total of 143 unselected autopsies (9%). The incidence increased with increasing age. The amyloid was classified using histochemistry, immunohistochemistry and clinical features. Eight cases were categorized as senile vesicle amyloid, two as systemic AA amyloid with secondary involvement of the seminal vesicle, and three as mixed amyloidosis. The morphological appearances of the different categories of seminal vesicle amyloidosis are similar but a different distribution is common. The staining characteristics of senile vesicle amyloid suggest that this is a different amyloid protein, perhaps locally derived within the seminal vesicle. PMID- 8454263 TI - The prevalence of tubo-endometrial metaplasia and adenomatoid proliferation. PMID- 8454264 TI - Subcutaneous, meningo-glial nodule--a novel lesion in the buttock of a neonate. PMID- 8454265 TI - Primary liver lymphoma associated with primary biliary cirrhosis. PMID- 8454266 TI - Villous adenoma of ileum in Lynch II syndrome. PMID- 8454267 TI - Clear cell carcinoid tumour of the stomach. PMID- 8454268 TI - Prostatic adenocarcinoma with a bizarre stromal cell reaction. PMID- 8454270 TI - Thyroglobulin in medullary thyroid carcinoma: immunohistochemical study with polyclonal and monoclonal antibodies. AB - The presence of thyroglobulin (TG) was investigated by immunohistochemistry with one polyclonal and three distinct monoclonal anti-TG antibodies in 19 primary and 15 metastatic medullary thyroid carcinoma (MTC) cases. In two primary tumors possessing a mixed trabecular and follicular growth pattern, a significant number of tumor cells were positive with the four antibodies in all parts of the tumor; these tumors were considered to be genuine mixed follicular and parafollicular tumors. The 17 other primary tumors looked like "classical" (ie, predominantly compact) MTC. Eight contained tubular or microfollicle-like structures that were consistently TG-negative. Eight contained residual entrapped normal follicles positive with the four anti-TG antibodies. In six cases isolated foci of tumor cells reacted with polyclonal antibody or monoclonal antibody 11. In 10 cases circulating TG stained positively with polyclonal antibody in vascular channels, five cases stained positively for TG with monoclonal antibody 11, four cases stained positively for TG with monoclonal antibody 7, and three cases stained positively for TG with monoclonal antibody 1. In metastases TG was found in tumor cells in only one instance, but positive reactions were obtained in vascular channels and macrophages in several cases. We conclude from this study that there is no genuine secretion of TG in classical, compact MTC, which differs morphologically and functionally from mixed follicular and parafollicular tumors secreting both TG and thyrocalcitonin. PMID- 8454269 TI - Study of Epstein-Barr virus early RNA 1 (EBER1) expression by in situ hybridization in thymic epithelial tumors of Chinese patients in Taiwan. AB - Forty-one thymic epithelial tumors from Chinese patients in Taiwan, including 14 noninvasive thymomas, seven invasive thymomas, and 20 thymic carcinomas, were investigated for the presence of Epstein-Barr virus transcripts by in situ hybridization using digoxigenin-labeled riboprobes for EBER1 expressions. None of the 14 noninvasive thymomas or seven invasive thymomas had detectable EBER1. Only one of 20 thymic carcinomas was positive for EBER1. This positive tumor was a lymphoepithelioma-like carcinoma found in a 19-year-old patient. Four different cases of lymphoepithelioma-like carcinoma were negative. Of note, the present case and all previously reported cases of Epstein-Barr virus-associated thymic carcinomas were lymphoepithelioma-like carcinomas. These results are consistent with those of several Western studies and do not support the view that there are geographic or racial differences affecting the role of Epstein-Barr virus in the pathogenesis of thymic epithelial tumors. PMID- 8454271 TI - Plexogenic angiopathy in pulmonary intralobar sequestrations: pathogenetic mechanisms. AB - Vascular remodeling to form plexiform (glomoid) lesions is a little-known manifestation of intralobar pulmonary sequestration. We describe histologic and immunohistochemical features of these lesions in resected specimens from three subjects aged 3, 19, and 28 years. The vascular changes, which included medial and intimal thickening, angioblastic proliferation, plexiform lesions, and dilation lesions, occurred in a setting of hypoxia, chronic inflammation, and high pressure and flow via a systemic arterial supply. We demonstrated strong immunoreactivity of the angioblastic tissue and the plexiform lesions with antibodies to muscle actin, alpha-smooth muscle actin, and vimentin, and weak to absent reactivity with antibody to desmin. We suggest that in these sequestrations plexiform lesions develop via angioblastic proliferation at arterial branch points and that dilation lesions develop from subsequent expansion of distal anastomoses. PMID- 8454272 TI - Breast lymphomas: a clinicopathologic review. AB - Primary lymphoma is an uncommon tumor in the breast. Review of the literature shows two distinct clinicopathologic groups. One, which affects young women, is frequently bilateral, is often associated with pregnancy, and is a Burkitt-type lymphoma. The second group affects older women, is usually B-cell non-Hodgkins type lymphoma, and presents clinical features identical to carcinoma of the breast. Three recent studies have suggested that up to half of the cases in the latter group belong to the category of lymphomas arising from the mucosa associated lymphoid tissues. We have identified nine cases of primary lymphoma from the files of Guys Hospital Clinical Oncology Breast Unit in the 16-year period from 1974 to 1990. The clinical features have been reviewed and the tumors have been evaluated both on a morphologic and an immunohistochemical basis, and seven of nine of the cases have been screened for t[14;18] translocation using the polymerase chain reaction. All the tumors occurred in women older than 50 years and who presented with features of mammary carcinoma. One tumor was true histiocytic lymphoma; the remaining eight cases were B-cell lymphomas. Seven of the latter cases were high-grade B-cell lymphomas and one was a true follicular lymphoma. None of our cases showed the features of lymphoma arising in mucosa associated lymphoid tissue. PMID- 8454273 TI - Pathology of the gallbladder in common bile duct obstruction: the concept of ascending cholecystitis. AB - The presence of intraepithelial aggregates of neutrophils in the gallbladder mucosa is proposed as a specific histologic marker of common bile duct obstruction. Medical records of 334 patients who underwent cholecystectomy over a 14-month period were reviewed. Based on clinical, laboratory, radiologic, and operative findings, 48 patients with common duct obstruction were identified. Pathologic changes of acute cholecystitis were found in eight patients. In the remaining 40 patients the proposed pathognomonic changes of biliary obstruction were observed. Sensitivity and specificity of the histologic criterion were 83.3% and 97.4%, respectively. On a pathophysiologic basis, the characteristic inflammatory response in the gallbladder mucosa is believed to be analogous to the reaction seen in the wall of the common bile duct and liver, and a part of the process of ascending cholangitis. In the absence of usual changes of acute cholecystitis, a pathologist may suggest the possibility of common duct obstruction if intraepithelial neutrophilic aggregates are seen on examination of the gallbladder. PMID- 8454274 TI - N-myc gene amplification/expression in localized stroma-rich neuroblastoma (ganglioneuroblastoma). AB - Using nucleic acid analysis and in situ hybridization we have demonstrated N-myc amplification and expression in two children with a localized (stages I and II) stroma-rich neuroblastoma (NB) (ganglioneuroblastoma). The phenomenon was observed in both undifferentiated and mature ganglion-like cells. The two children are alive and disease-free without any treatment after 16 and 17 months. These observations suggest that morphologic differentiation in NB in vivo is not necessarily followed by a decrease in N-myc expression. Moreover, N-myc amplification does not represent an adverse prognostic factor. In contrast with what happens in undifferentiated NB, N-myc amplification does not have an adverse effect on prognosis when occurring in localized (stages I and II), stroma-rich NB with a favorable histology. PMID- 8454275 TI - Architectural patterns of high-grade prostatic intraepithelial neoplasia. AB - High-grade prostatic intraepithelial neoplasia (PIN) is characterized by cellular proliferations within pre-existing ducts and glands with cytologic changes mimicking adenocarcinoma, including prominent nucleoli, but lacking stromal invasion. To determine the architectural spectrum of high-grade PIN, 60 serially sectioned radical prostatectomy specimens with PIN and cancer were reviewed. Four common patterns of high-grade PIN were identified, usually with multiple patterns in each case: tufting (in 87% of cases), micropapillary (in 85% of cases), cribriform (in 32% of cases), and flat (in 28% of cases). Tumor grade was not significantly associated with any pattern of PIN. Luminal cytoplasmic apical blebs were found in all cases regardless of the pattern of PIN. A variety of associated architectural and cytologic features were observed with high-grade PIN: epithelial arches (in 60% of cases), cellular trabecular epithelial bars (in 22% of cases), "Roman" bridges (in 30% of cases), partial gland involvement (in 82% of cases), basal cell layer disruption with glandular budding (in 23% of cases), large cystic gland involvement (in 10% of cases), involvement by nodular hyperplasia (in 5% of cases), microcalcifications (in 8% of cases), proteinaceous luminal secretions (in 62% of cases), corpora amylacea (in 55% of cases), exfoliated cells of PIN (in 42% of cases), luminal crystalloids (in 3% of cases), and mucinous metaplasia (in 2% of cases). High-grade PIN exhibits a variety of architectural patterns while retaining the distinctive cytoplasmic apical blebs and diagnostic nuclear and nucleolar features. Identification of high-grade PIN warrants a further search for invasive carcinoma, but should not influence or dictate decisions regarding definitive therapy. PMID- 8454276 TI - Papillary renal cell carcinoma: clinical implication of DNA content analysis. AB - Papillary renal cell carcinoma is considered a less-aggressive histomorphologic variant of renal cell carcinoma. We investigated the clinicopathologic features and the DNA ploidy pattern in 22 papillary renal cell carcinoma cases and correlated the findings to the patients' length of survival. In this study the demographic data were similar to those of previously published series. Histologically, two neoplasms were Fuhrman's nuclear grade 1, eight were nuclear grade 2, 11 were nuclear grade 3, and one was nuclear grade 4. Six tumors were stage I, three were stage II, five were stage III, and eight were stage IV. With a mean follow-up period of 42 months, eight patients died of disease and 14 were alive and well. DNA aneuploidy was found in 50% of the neoplasms and was frequently associated with high tumor nuclear grade, high tumor stage, and poor prognosis. Conversely, DNA diploidy was preponderantly noted in neoplasms with low tumor nuclear grade and stage, and none of the patients died of their disease. A statistically significant difference between DNA ploidy/tumor stage and patient outcome was obtained. No significant correlation between DNA ploidy and nuclear grade was observed. Our results suggest that DNA content measurements may assist in evaluating the clinical outcome of this neoplasm. Moreover, they indicate that papillary renal cell carcinomas manifest clinicopathologic, DNA content, and biologic characteristics akin to those of nonpapillary variants. PMID- 8454277 TI - Relationship between proliferative activity and ploidy level in a series of 530 human brain tumors, including astrocytomas, meningiomas, schwannomas, and metastases. AB - By identifying six DNA histogram types (diploid, hyperdiploid, triploid, hypertriploid, tetraploid, and polymorphic) in a series of 206 astrocytic tumors, we showed recently that patients with hypertriploid astrocytic tumors have a better possibility of survival than patients with other DNA histogram-type related tumors. In the present work DNA histogram type and proliferation index (S phase fraction) are characterized in a series of 530 adult tumors from the central and peripheral nervous systems. Of these 530 tumors, there were 79 nerve sheath tumors, 181 meningiomas, 221 astrocytic tumors, and 49 metastases. Analysis was performed by means of digital cell image examination of Feulgen stained nuclei from formalin-fixed, paraffin-embedded tumors. The data reveal that there was a majority of diploid tumors (66%) in the primary tumor group (nerve sheath tumors, meningiomas, and astrocytic tumors), while aneuploid tumors were in a marked majority (90%) in the secondary (metastatic) brain tumor group, with a predominance (47%) of the polymorphic tumor type. Independently of tumor histopathologic group, the hypertriploid-type tumors proliferated less actively than the five other types. Such a feature might partly explain the better prognosis associated with hypertriploid astrocytic tumors as compared with what occurs with respect to the other DNA histogram-type related tumors. PMID- 8454278 TI - Monocytoid B-cell lymphoma: its relationship to and possible cellular origin from marginal zone cells. AB - Monocytoid B-cell lymphoma, the neoplastic counterpart of the monocytoid B cells, is a now well-recognized variant of low-grade, malignant B-cell lymphomas. However, monocytoid B-cell lymphomas state of differentiation, its cellular origin, and its relationship to other B-cell compartments are still obscure. We investigated an unusual case of monocytoid B-cell lymphoma with generalized disease at presentation, including infiltration of the abdominal lymph nodes, spleen, liver, and bone marrow, as well as involvement of the peripheral blood. The tumor showed the typical sinusoidal and perifollicular growth pattern in the lymph nodes. In the spleen the main infiltrate was confined to the marginal zone. These features and the characteristic immunoreactivity of the tumor cells (KiM1P+, KiB3-) in our case suggest that monocytoid B cells and their neoplastic counterparts are closely related to and probably derived from marginal zone cells. PMID- 8454279 TI - Myasthenia gravis in a man with a history of chordoma: observations of muscle like antigens in carcinoma. AB - A 67-year-old white man with a remote history of a chordoma of the clivus presented with myasthenia gravis. We investigated the possibility that these conditions were related immunologically. Tissue sections of various chordoma specimens were reacted with dilutions of patient serum and control serum by an indirect immunoperoxidase method. In addition, sections were reacted with antibodies to muscle antigens. Of six chordomas, five reacted positively to patient serum. None reacted to control serum. One chordoma reacted positively to desmin, and all six reacted positively to myoglobin. We propose that the patient may have produced antibody to muscle-like antigens of the chordoma that subsequently cross-reacted with acetylcholine receptor and led to clinical myasthenia gravis. PMID- 8454280 TI - Arginase deficiency manifesting delayed clinical sequelae and induction of a kidney arginase isozyme. AB - Deficiency of liver arginase (AI) is characterized clinically by hyperargininemia, progressive mental impairment, growth retardation, spasticity, and periodic episodes of hyperammonemia. The rarest of the inborn errors of urea cycle enzymes, it has been considered the least life-threatening, by virtue of the typical absence of catastrophic neonatal hyperammonemia and its compatibility with a longer life span. This has been attributed to the persistence of some ureagenesis in these patients through the activity of a second isozyme of arginase (AII) located predominantly in the kidney. We have treated a number of arginase-deficient patients into young adulthood. While they are severely retarded and wheelchair-bound, their general medical care has been quite tractable. Recently, however, two of the oldest (M.U., age 20, and M.O., age 22) underwent rapid deterioration, ending in hyperammonemic coma and death, precipitated by relatively minor viral respiratory illnesses inducing a catabolic state with increased endogenous nitrogen load. In both cases, postmortem examination revealed severe global cerebral edema and aspiration pneumonia. Enzyme assays confirmed the absence of AI activity in the livers of both patients. In contrast, AII activity (identified by its different cation cofactor requirements and lack of precipitation with anti-AI antibody) was markedly elevated in kidney tissues, 20-fold in M.O. and 34-fold in M.U. Terminal plasma arginine (1500 mumols/l) and ammonia (1693 mmol/l) levels of M.U. were substantially higher than those of M.O. (348 mumols/l and 259 mumols/l, respectively). By Northern blot analysis, AI mRNA was detected in M.O.'s liver but not in M.U.'s; similarly, anti-AI crossreacting material was observed by Western blot in M.O. only. These findings indicate that, despite their more long lived course, patients with arginase deficiency remain vulnerable to the same catastrophic events of hyperammonemia that patients with other urea cycle disorders typically suffer in infancy. Further, unlike those other disorders, an attempt is made to compensate for the primary enzyme deficiency by induction of another isozyme in a different tissue. Such substrate-stimulated induction of an enzyme may be unique in a medical genetics setting and raises novel options for eventual gene therapy of this disorder. PMID- 8454281 TI - Rapid detection and prevalence of cholesteryl ester transfer protein deficiency caused by an intron 14 splicing defect in hyperalphalipoproteinemia. AB - A deficiency of plasma cholesteryl ester transfer protein (CETP) is one of the genetic causes of increased serum high density lipoprotein (HDL)-cholesterol levels (hyperalphalipoproteinemia). A splicing defect (G-->A mutation) at the +1 position of intron 14 of the human CETP gene is a common mutation in the Japanese CETP deficiency. A rapid screening method for the splicing defect by means of primer-specified restriction map modification was described. The frequency of the mutation in hyperalphalipoproteinemia was determined, and its frequency in the general population was estimated. During polymerase chain reaction (PCR) with a modified primer, a novel NdeI restriction endonuclease site was created from the mutated allele in the PCR products, which could be visualized after electrophoresis of the digested products. As a result, 21 of 121 unrelated hyperalphalipoproteinemic subjects with HDL-cholesterol > or = 60 mg/dl (1.55 mmol/l), were found to have the G-->A mutation. Of the 21 individuals, 8 were found to be homozygous for the mutation. Allele frequency of the mutation was 1.5% (1/68), 2.8% (2/72), 7.1% (4/56), and 47.8% (22/46) in the groups with HDL cholesterol levels of 60-79 mg/dl, 80-99 mg/dl, 100-119 mg/dl, and > or = 120 mg/dl, respectively. Based on the percentage of the area under the computed normal distribution curve of serum HDL-cholesterol, the frequency of the mutated allele in the general population was estimated to be 0.81% from the present results. This rapid detection method facilitates large-scale screening of CETP deficiency caused by the splicing defect. The mutation was frequent in Japanese subjects with hyperalphalipoproteinemia, especially in the group with HDL cholesterol > or = 120 mg/dl. PMID- 8454282 TI - Mapping of the gene for X-chromosomal split-hand/split-foot anomaly to Xq26 q26.1. AB - A large inbred kindred from Pakistan in which an isolated type of split hand/split-foot anomaly is transmitted as an X-chromosomal trait has previously been described. An X/autosomal translocation and an X-chromosomal rearrangement have been excluded by cytogenetic studies. In order to map the gene responsible for this disorder, linkage analysis has been performed by using 14 highly polymorphic DNA markers distributed over the whole X chromosome. Two-point linkage analysis between the disease locus and X-chromosomal marker loci gives maximal lod scores at theta = 0.00 with the loci DXS294 (Zmax = 5.13) and HPRT (Zmax = 4.43), respectively, suggesting that the gene for the X-chromosomal split hand/split-foot anomaly is localized at Xq26-q26.1. PMID- 8454283 TI - Aneuploidy detection in human sperm nuclei using fluorescence in situ hybridization. AB - Fluorescence in situ hybridization (FISH) was performed on human interphase sperm nuclei to determine the utility of this technique for aneuploidy detection. Repetitive DNA sequences specific for chromosomes 1, 12 and X were biotinylated and hybridized with mature sperm, which had been treated with cetyltrimethylammonium bromide and dithiothreitol to render them accessible to the probes. Detection of bound probe was accomplished with fluoresceinated avidin and antiavidin. For each of the chromosomes studied, chromosome number was determined by counting the fluorescent signals, representing hybridized regions, within the sperm nuclei. The frequencies for disomy, that is for nuclei containing two signals, for chromosomes 1, 12 and X were 0.06%, 0.04% and 0.03%, respectively. The congruence of these results with those determined by the cross species hamster oocyte-human sperm assay, and the high efficiency of hybridization indicate that FISH is a sensitive and reliable tool for aneuploidy detection in human sperm. PMID- 8454284 TI - A denaturing gradient gel electrophoresis assay for sensitive detection of p53 mutations. AB - p53 is a tumor suppressor gene located on 17p, a region of the human genome frequently deleted in tumors. Mutation of the p53 gene is an important step leading to development of many forms of human cancer. To simplify the analysis of tumors for p53 point mutations, we describe a GC-clamped denaturing gradient gel assay for detecting single-base substitutions within highly conserved regions of the p53 gene. This assay allows for efficient screening of tumors for single-base substitutions within the p53 gene and can be used to facilitate sequence analysis of p53 point mutations. PMID- 8454285 TI - Evaluation of routine prenatal ultrasound examination in detecting fetal chromosomal abnormalities in a low risk population. AB - Prenatal diagnosis performed by fetal ultrasound scan is now a routine part of antenatal care in many countries. We have used our registry of congenital malformations to determine how many fetal anomalies and consequently how many chromosomal abnormalities are detected by this procedure. In our region, evaluation of prenatal diagnosis of chromosomal abnormalities in women of 38 years and younger (chromosomal prenatal diagnosis is offered to women > or = 38 years) with no personal or familial history of chromosomal anomaly was performed in 119,099 consecutive pregnancies of known outcome from 1980 to 1987. At least one ultrasonographic examination seeking congenital malformations was performed in more than 95% of the pregnant women studied. The total number of chromosomal anomalies during the study period was 199, 123 of these being Down syndrome. Only 41 (34.5%) of the 119 fetuses with chromosomal abnormalities and congenital malformation examined had been found to have a malformation at ultrasound examination. This low sensitivity was different for the diverse chromosomal abnormalities. Only 10 out of the 54 fetuses with Down syndrome and malformations (18.5%) were detected and only 3 out of 24 (12.5%) atrioventricular canal defects in those trisomic 21 patients were detected. Only 5 out of 11 (45.4%) fetuses with trisomy 13, 13 out of 26 (50.0%) fetuses with trisomy 18, 7 out of 12 patients with monosomy X (58.3%) and 6 out of 27 (22.2%) fetuses with other chromosomal abnormalities were diagnosed. Moreover, the time of detection of these anomalies was early enough to allow amniocentesis and termination of pregnancy in the case of a chromosomal abnormality in only 15 out of these 41 patients, including 7 cases of cystic hygroma in fetuses with monosomy X. This low sensitivity is not the result of the quality of the ultrasound equipment. It may be explained by the inadequate qualification of some operators and by the insufficient duration of the routine examination. In conclusion, our study has shown that the sensitivity of the detection of chromosomal abnormalities by routine prenatal ultrasound screening is low. Other screening methods are needed. PMID- 8454286 TI - High-resolution cytogenetic characterization of telomeric associations in ring chromosome 19. AB - High-resolution cytogenetic studies of a normal individual with ring chromosome 19 indicate that, at the late-to-mid prophase level of band resolution, no apparent chromosomal material is missing, and that telomeric fusion/association, not deletion, is the cause of the ring chromosome formation. Sub-band analysis of the telomeric fusion shows thin chromatin filaments between the telomeres of some of the very elongated ring chromosomes, which cannot be resolved by metaphase chromosome analysis. The ring chromosome found in this individual shows evidence of the characteristic instability associated with ring chromosomes, including duplicated segments, double rings, and subsequent loss of the ring resulting in cells with monosomy 19. The lack of phenotypic effect and the unstable ring behavior, unlike previously reported patients with ring 19, support the formation of this ring by telomeric association. PMID- 8454287 TI - X-linked myoclonus epilepsy explained as a maternally inherited mitochondrial disorder. AB - A family with myoclonus epilepsy has been described previously as suffering from an X-linked disorder, because at least four males were affected, and only mild and variable symptoms were seen in some female carriers. In this family, we have now identified a mitochondrial A-->G (8344) heteroplasmic point mutation. This point mutation has been described in families with maternally inherited myoclonus epilepsy and ragged red fibers. The degree of severity of the disorder in the different family members was reflected in the relative quantity of mutated mitochondrial DNA. It is concluded that the mode of inheritance in this family is not X-linked but maternal. PMID- 8454288 TI - Linkage of Van der Woude syndrome (VWS) to REN and exclusion of the candidate gene TGFB2 from the disease locus in a large pedigree. AB - Van der Woude syndrome (VWS) is an autosomal dominant disorder associated with one or more of the following features: clefting of the primary or secondary palate, hypodontia or lower lip pits. It has been estimated to account for 2% of all cases of cleft lip and palate. VWS is one of the rare disorders in which clefting of the primary and secondary palate may be seen to segregate as components associated with the same gene. Because of its autosomal dominant inheritance, VWS is readily accessable to linkage analysis as a preliminary step in the identification of the molecular abnormality underlying the clefting effect in the primary and secondary palate. A reported linkage between REN and VWS has promoted us to use pHRnX3.6 (REN) and several markers surrounding REN for a linkage analysis in a large Swiss family. In a second step, linkage analysis was performed to study restriction fragment length polymorphisms for the candidate gene TGFB2 and other loci recently mapped to the candidate region 1q32-1q41. Evidence for linkage (theta = 0.00, lod score = 3.01) between REN and VWS could be confirmed in this pedigree. TGFB2 demonstrated recombination with the disease locus and is unlikely to be causative in VWS. The results of a multipoint linkage analysis showed that VWS was flanked by D1S65 and TGFB2 at a maximum location score of 20.3. PMID- 8454289 TI - Four separate regions on chromosome 17 show loss of heterozygosity in familial breast carcinomas. AB - Two genes predisposing females to autosomal dominant breast cancer are located on chromosome 17. Mutations in the p53-gene on the short arm have been shown to predispose females to early onset breast cancer in families with the rare Li Fraumeni syndrome. Another locus on 17q (BRCA1), was found to be linked to the disease in a subset of families with breast cancer. In order to determine the involvement of tumour suppressor genes at these loci in tumour development, we studied allele losses for markers on chromosome 17 in 78 familial breast carcinomas. The analysis used six polymorphic DNA markers, three on each arm. We found support for at least four separate regions displaying allele losses on chromosome 17: the p53-region, the distal part of 17p, the BRCA1 region and the distal part of 17q. The frequency of allele losses on distal 17p (16%) is low in these familial tumours compared with the previously reported incidence in sporadic tumours (> 50%), whereas the frequency of losses at the p53 locus and on 17q was similar to sporadic tumours (5%-40%). These data suggest that several regions on chromosomal 17 can harbour tumour suppressor genes involved in tumour development of familial breast cancer. PMID- 8454290 TI - Cystic fibrosis in Spain: high frequency of mutation G542X in the Mediterranean coastal area. AB - We have determined the frequency of deletion delta F508 and mutation G542X, a nonsense mutation in exon 11 of the cystic fibrosis (CF) gene, in a sample of 400 Spanish CF families. Mutation G542X represents 8% of the total number of CF mutations in Spain, making it the second most common mutation after the delta F508 deletion, which accounts for 48% of CF chromosomes. G542X has a higher frequency in the Mediterranean coastal area (14%) and in the Canary Islands (25%). About 70% of G542X chromosomes are from Andalucia, Murcia, Valencia, Catalunya and the Canary Islands. The delta F508 deletion has its highest frequency in the Basque Country (83%). Mutation G542X is associated with the same rare haplotype that is found in association with the delta F508 mutation. The haplotype homogeneity found for G542X, even when intragenic microsatellites (IVS8CA, IVS17BTA and IVS17BCA) are considered, allows us to postulate that this mutation arose from a single mutational event. The geographic distribution of mutations delta F508 and G542X suggests that delta F508 was present in the Iberian Peninsula before the Indo-European invasions, and that G542X was introduced into Spain, via the Mediterranean Sea, probably by the Phoenicians, between 2500 and 3000 years ago. PMID- 8454291 TI - Hereditary recombined three-allele variant of the Gc system. AB - A three-allele variant with Gc 2, Gc 1F and Gc 1A2 alleles was detected in both a baby and his mother during paternity testing by isoelectric focusing. His father had a normal Gc phenotype, Gc 2-1F. Further examination of his mother's relatives revealed that his grandfather also had the same three-allele variant, while his grandmother and his aunt had normal Gc 2-1F and Gc 2-2. From these results, it was considered that the Gc 1F and Gc 1A2 alleles were on the same single chromosome. It was suggested that recombination had occurred between two chromosomes that had the Gc 1F and Gc 1A2 allele, respectively, forming the variant allele Gc 1F1A2 on a single chromosome. PMID- 8454293 TI - Sequence variant of the human cathepsin G gene. PMID- 8454292 TI - DXS539, a polymorphic DNA marker proximal of the fragile-X gene. AB - We report a new polymorphic DNA marker (pJH89, DXS539) proximal to the fragile-X site. The pJH89 probe identifies a TaqI and a NcoI restriction fragment length polymorphism (combined heterozygosity of 42%) and is linked to the fragile-X locus with a maximal LOD score of 12 at 4 cM. Multipoint linkage analysis and physical mapping studies indicate that the pJH89 probe is located within in the interval defined by the markers DXS369 and DXS548. PMID- 8454294 TI - D21S210: a highly polymorphic (GT)n marker closely linked to the beta-amyloid protein precursor (APP) gene. AB - We describe a highly polymorphic (GT)n repeat with 14 alleles that is closely linked to the amyloid precursor protein (APP) gene on human chromosome 21. This marker, D21S210, will be useful for studies of linkage of disorders such as Alzheimer disease to the APP gene. PMID- 8454295 TI - Exclusion of the biglycan (BGN) gene as a candidate gene for the Happle syndrome, employing an intragenic single-strand conformational polymorphism. PMID- 8454296 TI - Mode of interaction between tumor necrosis factor alpha and a monoclonal antibody expressing a recurrent idiotype. AB - Tumor Necrosis Factor alpha (TNF alpha) is an inflammatory cytokine which exists mainly as a 51kD complex built up of 3 identical, noncovalently-linked polypeptide subunits. We have raised monoclonal antibodies (mAb) against human TNF alpha (huTNF alpha). One of these mAb (mAb78, mouse IgG1k) was studied in detail. mAb78 expresses a recurrent idiotype typical of the BALB/c anti-huTNF alpha antibody response. HuTNF alpha bound to mAb78 with an affinity constant (Kobs) of 3.2 x 10(10)M-1. The number of huTNF alpha-binding sites per mAb78 molecule was approximately 0.7. At concentrations higher than the Kobs mAb78 neutralized huTNF alpha at a approximately 1.3:1 molar ratio. mAb78 precipitated huTNF alpha in a double immunodiffusion assay in agar. Gel-filtration experiments of mAb78-huTNF alpha mixtures, that had been set up in large antigen excess, detected complexes of 570 kD as the smallest ones formed under these conditions. We propose that these results are accommodated best by a model according to which cyclic complexes built up of 3 mAb78 and 2 huTNF alpha molecules are the smallest units formed upon interaction of the reagents. In view of this model we discuss how huTNF alpha and mAb78 can undergo a precipitin reaction. PMID- 8454297 TI - Monoclonal antibodies against methionyl recombinant human prolactin. AB - Hybridoma cell lines producing monoclonal antibody (Mab) against recombinant human prolactin (rhPrl) were established from fusion between X63-Ag8 myeloma cells and Balb/c mice splenocytes. Four Mabs numbered I to IV were selected by ELISA, purified and characterized. All these Mabs were of the Ig1 kappa isotype and able to recognize oxidized as well as reduced rhPrl. As shown by a competitive inhibition assay, Mab IV did not compete with any of the three others. Moreover, both rhPrl and hPrl extracted from human pituitaries, were recognized equally by this Mab. Properties displayed by Mab IV make it very attractive for the evaluation of prolactin levels by sandwich immunoassays. PMID- 8454298 TI - The use of transformed T cell lines for clonal expansion of human B cells from peripheral blood, spleen, and tumor-infiltrating lymphocytes. AB - Human transformed T cell lines were able to induce polyclonal B cell activation and immunoglobulin (Ig) secretion from peripheral blood mononuclear cells, spleen cells and tumor-infiltrating lymphocytes (TIL). Cells from one of the lines tested, MOT, did not require any exogenous stimuli to induce maximal responses and under similar conditions induced higher levels of response than peripheral blood T cells or other T cell lines. MOT-induced B cell activation and Ig secretion required cell contact and factors present in the MOT culture supernatant. MOT cells induced B cell responses from TIL in the three tumors tested (melanoma, ovarian and colon cancer) and HIV-specific immunoglobulin secretion by spleen cells from an HIV+ patient. PMID- 8454299 TI - Effect of murine ascites on the ability of hybridoma cells to produce antibody and proliferate in vitro. AB - Murine ascites has been shown to contain a variety of growth promoting activities. In this study, we examined the effects of ascites fluid on the efficiency of hybridoma production and cell growth. SP2/0 mouse myeloma cells were injected into peritoneal cavities of mice and ascitic fluid was collected. Lymphocytes from mice immunized with porcine growth hormone (pGH) were fused with myeloma cells in a standard hybridization procedure. These cells were then dispensed in 96-well plates in medium containing either 2.5% ascites or 20% fetal calf serum (FCS) and cultured for few days. Supernatants from these cultures were collected and analyzed for anti-pGH antibodies. It was demonstrated that ascites supplemented medium increased the efficiency in generating specific antibody secreting hybridomas by 4-fold over FCS-supplemented medium. Furthermore, hybridoma cells were cultured in microtiter plate and found to proliferate in response to ascites in a dose dependent manner. This effect was abolished by prior digestion of ascites with trypsin, indicating its protein nature. B lymphocyte related cytokines seemed less likely involved because antibodies to IL 4 and IL-6 failed to alter the stimulatory effect of ascites. Ascites was fractionated by FPLC using Superose 12 column and the active moiety was found to be a small m.w. peptide (< 1,000 dalton). Therefore, murine ascites is capable of substituting for conventional FCS in culture medium in the area of hybridoma technology. PMID- 8454300 TI - A rapid procedure for purifying IgM monoclonal antibodies from murine ascites using a DEAE-disk. AB - A method for purifying IgM monoclonal antibodies (mAbs) from murine ascites using a DEAE-disk is described. After ammonium sulfate precipitation, ascites proteins are redissolved and loaded onto a DEAE-disk. MAb then is eluted from the disk using a stepwise NaCl gradient. IgM mAb produced by this procedure was > 95% pure as assessed by reducing SDS-PAGE analysis and was free of significant IgG contamination as determined by double radial immunodiffusion analysis. Yield of IgM mAb was approximately 2% of total ascites protein and approximately 10% of the amount of IgM contained in crude ascites. MAb retained immunoreactivity as assessed by ELISA, and the affinity index was evaluated by thiocyanate elution and remained unchanged. This two step technique for purifying IgM mAb from murine ascites is rapid, simple, and yields mAb of sufficient purity and immunoreactivity for the majority of mAb applications. PMID- 8454301 TI - Chicken anti-protein G for the detection of small amounts of protein G. AB - Streptococcal protein G, similar to staphylococcal protein A, is the Fc-binding proteins that seems best suited for affinity-purification of mouse, rat or human monoclonal antibodies. We have developed a sandwich-ELISA for monitoring of protein G leakage from such columns. It utilizes microtitre plates coated with chicken anti-protein G to capture protein G, and biotinylated chicken anti protein G to detect bound protein G. Chicken IgG is one of a very few IgG that does not show any Fc reactivity with protein G. It is thus possible to make an antigen-specific assay for protein G. This assay can be used to detect protein G in IgG containing solutions, such as monoclonal antibody preparations. The method can be used to detect 1 x 10(-7) g protein G/1 in the presence of human serum or human IgG. PMID- 8454302 TI - Cloning of cDNAs encoding the variable domains of antibody BrE-3 and construction of a chimeric antibody. AB - BrE-3 is an IgG1,kappa murine monoclonal antibody that binds to human breast epithelial mucin and that has been shown to be promising for imaging and treatment of breast cancer. We have cloned and sequenced cDNAs encoding the variable regions of the light (VL) and heavy (VH) chains of BrE-3. VL belongs to group II and resulted from a V kappa-J kappa 1 fusion. VH belongs to group IIIc and arose from a V-D-JH3 non-conservative fusion which left little or nothing of the original D minigene. Thus, the third VH CDR contains only 4 amino-acids. We constructed an IgG1,kappa human/mouse chimeric antibody (by joining the murine variable domains to human constant domains) and expressed it in SP2/0 myeloma cells. This chimeric monoclonal antibody stains breast carcinoma tissue sections by the ABC immunoperoxidase method. Its affinity for the BrE-3 antigen is 2.68 x 10(8) M-1, which, considering the experimental error, is indistinguishable from the affinity of the original murine antibody (3.75 x 10(8) M-1). The VL and VH domains alone are respectively 73%, and 63% identical to the human V kappa II and VHIII consensus sequences. If the CDRs are excluded, these numbers become respectively 82% and 80%. Therefore, we expect the reported chimeric BrE-3 to be considerably less immunogenic to humans than the original murine antibody, while retaining the original binding properties. PMID- 8454303 TI - Monoclonal ligand binding site related anti-idiotypic antibodies elicited with a polyclonal kinin antibody. AB - Splenocytes from mice immunized with homogenous, polyclonal, rabbit kinin antibody (BK21) were fused using polyethylene glycol with the mouse myeloma cell line SP2/o. Eleven monoclonal antibodies, whose binding to BK21 could be inhibited by bradykinin, were obtained from 3 fusions. All of these anti idiotypic antibodies were of the IgG1k isotype, except for one, which was an IgG2ak. An IgMk, auto-anti-idiotypic antibody, reactive with BK21 was obtained from a fusion of SP2/o cells and splenocytes from a mouse immunized with bradykinin conjugated with carbodiimide to keyhole limpet hemocyanin. Bradykinin could completely inhibit the binding of all of the anti-idiotypic antibodies to BK21 in an enzyme-linked immunosorbent assay. This result is consistent with the anti-idiotypic antibodies being reactive with the ligand binding sites of BK21. It was possible to separate the anti-idiotypic antibodies into 2 groups. The first group, 10 of the 12 antibodies tested, was more sensitive to inhibition by bradykinin than the second group and was not readily inhibited by des-Arg9 bradykinin. The second group was about 7 times more sensitive to inhibition by des-Arg9-bradykinin than by bradykinin. Further experiments will be needed to determine whether or not these monoclonal anti-idiotypic antibodies are "internal image" antibodies. PMID- 8454304 TI - Elicitation and immunological characterization of monoclonal anti-idiotypic antibodies reactive with the ligand binding sites of monoclonal kinin antibodies. AB - Ten monoclonal anti-idiotypic antibodies (mAB2s) were obtained from fusions of myeloma cells, X63/Ag8.653, and splenocytes from mice immunized with one of two monoclonal kinin antibodies (mAB1s). The interactions of these mAB2s, with four different mAB1s, which have similar kinin binding specificities, was examined. Five of the ten mAB2s cross-reacted with similar affinities, with all four mAB1s. In addition, these five mAB2s were able to inhibit biotinylated-kallidin binding to the mAB1s. This indicated that these mAB2s interact with the mAB1s at, or near, their ligand binding sites. These immunological results are consistent with these five mAB2s being "internal image" beta type anti-idiotypic antibodies. PMID- 8454306 TI - Effects of transforming growth factor-beta 1 on the extracellular matrix and cytoskeleton of cultured astrocytes. AB - The present study was performed on primary cultures and subcultures of cerebellar astrocytes in order to investigate the effects of transforming growth factor-beta 1 (TGF beta 1) on proliferation, extracellular matrix (ECM) components, and cytoskeletal structures in relation to morphological changes. The expression and cellular distribution of the ECM components laminin and fibronectin and the cytoskeletal proteins glial fibrillary acidic protein (GFAP) and actin were investigated by immunoblotting, immunocytochemistry, and phalloidin staining. The proliferation of primary cultures was strongly inhibited by TGF beta 1. Treated cells became enlarged and spread onto the substratum. TGF beta 1 promoted the appearance of actin stress fibers and increased the cell actin content. It elicited a slight increase in GFAP expression and induced dispersion of thin filaments of GFAP. TGF beta 1 also stimulated the production of laminin and fibronectin and their incorporation into the ECM of primary cultures grown in medium with or without serum. Astrocytes grown in serum-containing medium for 1 day after subculturing responded strongly to TGF beta 1. Changes promoted by TGF beta 1 in cell shape, cytoskeleton, and ECM production of cultured astrocytes may have relevance for understanding the mechanisms of action of TGF beta 1 during brain development. PMID- 8454305 TI - The monoclonal antibody BQ16 identifies the alpha 6 beta 4 integrin on bladder cancer. AB - Monoclonal antibody BQ16, raised against UM-UC-9, a human bladder cancer cell line, exhibited strong reactivity with most bladder carcinoma tissue samples and cell lines. In normal urothelium, BQ16 stained only the basal surface of urothelial cells at the junction with the lamina propria. BQ16 immunoprecipitated two protein bands of approximately 140 and 180 kDa (under non-reducing conditions), while on Western blots, BQ16 identified only the 140 kDa protein indicating that BQ16 binds to one chain of a dimeric protein complex. The dimeric structure, molecular size, and basal orientation of the BQ16 antigen prompted a comparison with the alpha 6 beta 4 integrin identified by monoclonal antibody UM A9. In most tissues BQ16 and UM-A9 produced identical staining patterns. However, normal lymphocytes and certain bladder cancer cell lines were BQ16 positive but failed to react with UM-A9, indicating that the BQ16 and UM-A9 epitopes can be expressed independently. Pulse-chase immunoprecipitation experiments showed that the alpha 6 subunit was more prominent in early BQ16 precipitates and the beta 4 subunit was more prominent in early UM-A9 precipitates. Furthermore, preclearing cell extracts with the anti-alpha 6 antibody GoH3 removed all BQ16 reactivity and in UM-A9-negative, BQ16-positive cells, BQ16 precipitated the alpha 6 beta 1 complex. We conclude that BQ16 identifies the alpha 6 integrin subunit and that alpha 6 beta 4 integrin is strongly expressed in most bladder cancers. PMID- 8454307 TI - Transforming growth factor-betas inhibit mitogen-stimulated proliferation of astrocytes. AB - We have studied the influence of three members of the transforming growth factor beta (TGF-beta) family of multifunctional growth factors on the proliferation of cultured astrocytes isolated from newborn mouse cerebral cortex. Although TGF beta s 1, 2, and 3 cause only a small reduction in the low level of astrocyte proliferation occurring in chemically defined medium, they each inhibit the effects of five astrocyte mitogens (bFGF, EGF, PDGF, IL-1 alpha, and IL-2). Inhibition is observed when astrocytes are exposed to mitogen and TGF-beta at the same time and when they are exposed to TGF-beta prior to, and separately from, mitogen. This latter effect appears to be due to the binding of TGF-beta s to astrocyte-secreted extracellular matrix. These findings raise the possibility that TGF-beta may co-operate with other growth factors to control astrocyte proliferation in vivo. PMID- 8454308 TI - Interleukin-1 and tumor necrosis factor-mediated regulation of C3 gene expression in human astroglioma cells. AB - In this report, we show that in the human astroglioma cell line D54-MG, both interleukin-1 (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) enhance C3 gene expression in a time- and dose-dependent manner. Kinetic analysis demonstrates that after 96 h, C3 mRNA levels increase approximately 30-fold and 20-fold in response to IL-1 beta or TNF-alpha, respectively. C3 protein production increases proportionally, reaching levels 36-fold and 18-fold higher than untreated controls upon exposure to IL-1 beta or TNF-alpha, respectively. D54-MG cells require a minimal 1 h exposure to IL-1 beta in order to enhance C3 gene expression significantly, while 4 to 8 h are required for TNF-alpha. Simultaneous treatment of D54-MG cells with IL-1 beta and interferon-gamma (IFN gamma) resulted in an additive increase in both C3 mRNA and protein expression, a finding not seen with the combination of TNF-alpha and IFN-gamma. Primary rat astrocytes also express increased C3 mRNA levels after 48 h in response to IL-1 beta (5.3-fold increase) and TNF-alpha (7-fold increase), while an additive effect was observed upon simultaneous treatment with both IL-1 beta and IFN gamma. In the central nervous system (CNS), endogenous complement and cytokine production by astrocytes, and enhancement by IFN-gamma, a product of activated T cells often seen in the CNS in neural autoimmune disease, may contribute to the pathogenesis of inflammatory demyelinating diseases such as multiple sclerosis. PMID- 8454309 TI - Appearance of GFAP-positive cells in adult human brain cultures spontaneously decelerated in growth. AB - Cell cultures were derived from adult human brain biopsies [from cortical gray (cultures 9-HB-G and 33-HB-G) and white (culture 14-HB-W) and stroke-injured white matter (culture 33-HB-IW)]. The morphology and growth rate of cultured cells were examined and correlated with the presence of vimentin and glial fibrillary acidic protein (GFAP). The cultures from various brain matters differed in cell morphology and rate of growth but not in GFAP and vimentin staining. Cells of primary and rapidly proliferating cultures were GFAP-negative and vimentin-positive. Spontaneous growth deceleration occurred in culture 14-HB W within passages 5 to 10 and in cultures 9-HB-G, 33-HB-G, and 33-HB-W within passages 17 to 20. This deceleration, as well as the successive complete growth arrest, were accompanied by an appearance of GFAP-positive cells and an elevated intensity for vimentin staining. We propose that GFAP-positive astrocytes originate from glial precursor cells that migrate from the explants and differentiate under prolonged subcultivation. PMID- 8454310 TI - Distinct effects of bFGF and PDGF on oligodendrocyte progenitor cells. AB - We have compared the effects of platelet-derived (PDGF) and basic fibroblast (bFGF) growth factors on the shape, migration, and differentiation of oligodendrocyte progenitor cells, the precursors of myelin-forming cells in the CNS. In the presence of bFGF, oligodendrocyte progenitors purified from rat neonatal brain cultures were stellate, non-motile, and had a morphological complexity of 1.26 +/- 0.03 as measured by fractal dimension (D). These cells expressed transcripts encoding the POU-homeodomain transcription factor Oct-6, but not myelin genes. Upon addition of PDGF, bFGF-treated cells became motile and twofold less complex in shape (D = 1.19 +/- 0.03). These changes occurred within 6 +/- 4 h and were dependent on de novo transcription and translation, but not DNA synthesis. Upon removal of PDGF the cells reverted to their stellate shape (D = 1.26). Removal of both bFGF and PDGF resulted in oligodendrocyte differentiation after 3 days, with a fourfold increase in complexity of shape (D = 1.55 +/- 0.08), loss of Oct-6 transcripts, and gain of myelin transcripts. Thus PDGF is both necessary and sufficient to induce a motile state in progenitor cells growing in the presence of bFGF. Together with our previous data (McKinnon et al.: Neuron 5:603, 1990), our results suggest that bFGF and PDGF may control distinct phases of proliferation and migration of oligodendrocyte progenitor cells in vivo. PMID- 8454311 TI - State rate regulation and inpatient mortality rates. AB - Most research on hospital rate regulation has focused on costs, but concern about its consequences for quality of care, particularly mortality rates, has also been raised. In this study mortality rates and standardized mortality ratios (SMR) were computed to estimate any effect on quality, using data about Medicare beneficiaries hospitalized during 1986. Regulated states had lower SMRs for both patients and the general population than unregulated states and admitted significantly fewer patients. We found no basis for concluding that rate regulation is adversely related to patient mortality or population mortality, despite lower admission rates. PMID- 8454312 TI - Sole providers of hospital care in rural areas. AB - This study examines the possibility of developing alternative targeting criteria for identifying small rural hospitals that serve as the sole providers of hospital care in their market areas. Compared to facilities currently targeted under Medicare payment policies, high market share hospitals are larger, less isolated facilities that deliver more complex care to their patients than other rural hospitals. They do not appear to serve vulnerable patient populations. Most importantly, these facilities appear to be financially viable and are likely to continue to provide services to their patients. The results of the study suggest that appropriate targeting criteria for identifying essential access facilities for reimbursement policy should focus on both structural characteristics and utilization patterns. PMID- 8454313 TI - Questions and answers. PMID- 8454314 TI - Impact of the Catastrophic Coverage Act and new coverage guidelines on Medicare skilled nursing facility use. AB - The promulgation of new coverage guidelines and provisions of the 1988 Medicare Catastrophic Coverage Act indicated that Medicare's role in financing nursing home care could expand greatly. This paper presents a facility-level analysis addressing how the policy changes affected the payer mix of subgroups of Medicare certified skilled nursing facilities (SNFs). Our analysis found that the new policies increased participation of nursing homes in the Medicare SNF program and suggested that the policies expanded both access to the Medicare SNF benefit and the role of public financing for nursing home care. Greater responsiveness to the policies was observed among proprietary SNFs and among those with more beds. PMID- 8454315 TI - Development of a resource-based patient classification scheme for rehabilitation. AB - Efforts are currently underway to develop a prospective payment system for inpatient medical rehabilitation. In this study, a clinically based, condition specific patient classification scheme was developed that includes 33 patient groupings, referred to as Functional Related Groups (FRGs). Each FRG is comprised of patients with similar clinical characteristics and resource use, as measured by length of stay. From a policy perspective, the FRGs minimize the adverse incentives that may develop in the selection of patients for admission to the rehabilitation facility. The FRGs, therefore, may be used as a basis in the development of a prospective reimbursement system for rehabilitation services. PMID- 8454316 TI - Validating risk-adjusted mortality as an indicator for quality of care. AB - Risk-adjusted mortality is perhaps the most commonly referenced outcome indicator for assessments of hospital quality. While mortality rate possesses considerable intuitive appeal as a quality indicator, scientific evidence concerning its appropriateness for this purpose is mixed. In this paper, we use a computerized discharge database to model mortality risks for patients hospitalized for three different conditions: cardiac disease (ischemic heart disease, coronary artery disease, angina, and left ventricular aneurysm), acute myocardial infarction, and septicemia. We then use a database of peer review quality findings to determine whether the ratio of observed to expected deaths in each of these conditions relates validly to quality. The results of our analyses provide strong support for the validity of one of our mortality indicators, weak support for another, and no support for the third. We conclude that before inferences about hospital quality are made using any risk-adjusted mortality indicator, the validity of the quality/outcome relationship must be established explicitly for that measure. PMID- 8454317 TI - Personal characteristics and spells without health insurance. AB - People without health insurance differ not only in their personal characteristics and reasons for being without health insurance but also in the length of time they spend in uninsured spells. A hazard model of spell durations is used to estimate the relative effects of a person's characteristics in the month just before an uninsured spell begins on the duration of the spell. Using the Survey of Income and Program Participation, our analyses indicate that monthly family income, educational attainment, and industry of employment in the month prior to losing health insurance are the characteristics that have the greatest impact on the exit rate from being without health insurance. Because low-income people could end an uninsured spell with either private health insurance or Medicaid, findings from an exploratory competing risks model are also reported. PMID- 8454318 TI - Spells without health insurance: the distribution of durations when left-censored spells are included. AB - In a previous paper (1990), we estimated the distribution of durations of uninsured spells for which the beginning could be observed. We raised the concern that uninsured spells that were in progress when the Survey of Income and Program Participation began might not be proportionally represented in a sample of uninsured spells restricted to spells with observed beginnings. This paper includes spells in progress when SIPP began. Including left-censored spells, and correcting for length bias inherent in such spells, does not fundamentally change our previous estimate of the distribution. PMID- 8454319 TI - Medical student indebtedness and choice of specialization. AB - This study's purpose was to examine the impact of indebtedness on medical student choice of specialty. Nonprimary care was disaggregated into distinct specialties. The study found that indebtedness induced medical students to choose the remunerative field of anesthesiology but had the opposite effect on the decision to choose the comparably remunerative field of radiology. The results imply that if specialties are aggregated into broad categories, such as primary and nonprimary care, the estimated impact of indebtedness on specialty choice may be misleading. Such estimates may also be biased if the type of medical school attended (public or private) is not included as a control variable. PMID- 8454320 TI - Relationship between early readmission and hospital quality of care indicators. AB - Readmission rates are being proposed as an outcome indicator of hospital-level quality despite the lack of evidence of a relationship between a readmission and the quality of care provided during the preceding hospital stay. This study examined this relationship by comparing the quality of care provided to samples of 134 unplanned readmissions and 158 nonreadmissions from 50 Department of Veterans Affairs medical centers. Four groups of commonly used quality indicators and seven readmission risk factors were included in a logistic regression analysis. Inclusion of the quality indicators significantly increased the predictive power of the logistic models, with "unexpected transfer to a special care unit" being the only significant variable. PMID- 8454321 TI - Toxoplasma gondii: a protozoan for the nineties. PMID- 8454322 TI - LasR of Pseudomonas aeruginosa is a transcriptional activator of the alkaline protease gene (apr) and an enhancer of exotoxin A expression. AB - The lasR gene of Pseudomonas aeruginosa is required for transcription of the genes for elastase (lasB) and LasA protease (lasA), two proteases associated with virulence. We report here that the alkaline protease gene (apr) also requires the lasR gene for transcription. Alkaline protease mRNA was absent in the lasR mutant PAO-R1 and present when an intact lasR gene was supplied in trans as determined by Northern (RNA) analysis. The lasR gene also enhances exotoxin A production. Exotoxin A activity in supernatants of PAO-R1 were 30% less than in supernatants of the parental strain, PAO-SR. Multiple copies of lasR in trans in PAO-R1 in increased toxin A activity to twice the parental levels. Analysis of PAO-R1 containing the toxA promoter fused to beta-galactosidase suggests that LasR acts at the toxA promoter or at upstream toxA mRNA sequences. beta-Galactosidase activity was approximately 40% lower in PAO-R1 than in the parental strain, PAO SR. Furthermore, the effect of LasR on the toxA promoter is not due to the stimulation of transcription of regA, a transcriptional activator of toxA. No difference in chloramphenicol acetyltransferase (CAT) activity was noted between PAO-SR and PAO-R1 containing transcriptional regA promoter-CAT gene fusions. These results broaden the regulatory dominion of lasR and suggest that the lasR gene plays a global role in P. aeruginosa pathogenesis. PMID- 8454323 TI - Temporal relationship of cytokine release by peripheral blood mononuclear cells stimulated by the streptococcal superantigen pep M5. AB - We undertook this study to determine the quality, quantity, and temporal relationship of pep M5-induced cytokine release. The ability of pep M5 to stimulate interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) production by a T-cell-depleted, monocyte- and B-cell-enriched cell population was dependent on the presence of T cells. The requirement for T cells could be met by addition of exogenous gamma interferon (IFN-gamma). In the presence of IFN gamma, pep M5 induced the release of TNF-alpha, IL-1, and IL-6, TNF-alpha levels peaked at 24 h, while IL-1 and IL-6 levels peaked at 48 h. pep M5 induced T cells to produce IFN-gamma, which may have accounted for the ability of the super antigen to induce the production of IL-1, IL-6, TNF-alpha, and TNF-beta by peripheral blood mononuclear cells (PBMC). The addition of excess IFN-gamma to cultures of pep M5 and PBMC did not further increase the release of these cytokines at 24 and 48 h but resulted in sustained higher levels at 72 h. Interestingly, TNF-beta production occurred only in the presence of pep M5 and exogenous IFN-gamma. The ability of pep M5 to induce cytokine production was compared with that of a potent super antigen, staphylococcal enterotoxin B (SEB). SEB was a 2- to 14-fold-more-potent inducer of IFN-gamma production. Furthermore, the profile of cytokine released by PBMC in response to this super antigen mimicked that seen with pep M5 in the presence of exogenous IFN-gamma. In conclusion, pep M5 induces the production of cytokines that are involved in immune regulation and inflammation. These cytokines also play a major role in human T-cell responses to this super antigen. PMID- 8454325 TI - Characterization of a catalase-deficient strain of Neisseria gonorrhoeae: evidence for the significance of catalase in the biology of N. gonorrhoeae. AB - We obtained a catalase-deficient (Kat-) strain of Neisseria gonorrhoeae isolated from a patient who had been unsuccessfully treated with penicillin. Quantitative enzyme assays and electrophoresis of cell extracts on native polyacrylamide gels subsequently stained for catalase and peroxidase activities failed to detect both enzymes. The strain exhibited no growth anomalies or unusual requirements when grown under ordinary laboratory conditions. However, the Kat- strain proved extremely sensitive to exogenous hydrogen peroxide, and analysis of the bacterial DNA after such exposure showed extensive single-strand breakage in both chromosomal and plasmid DNAs. Partial characterization of the gonococcal catalase from a Kat+ laboratory strain revealed that the enzyme had the physical and chemical properties of both catalase and peroxidase. PMID- 8454324 TI - Lipid modification of the 17-kilodalton membrane immunogen of Treponema pallidum determines macrophage activation as well as amphiphilicity. AB - A murine monoclonal antibody specific for a 17-kDa major membrane immunogen of Treponema pallidum was used to select recombinant Escherichia coli clones expressing the molecule from a T. pallidum genomic library. Sequence analysis of the structural gene for the immunogen (designated tpp17) revealed a 468-bp open reading frame encoding a polypeptide of 156 amino acids with a calculated molecular mass of 16,441 Da. The deduced amino acid sequence included a putative leader peptide terminated by a consensus tetrapeptide for the modification and processing of prokaryotic lipoproteins. Immunoprecipitation of the cloned immunogen radiolabeled with [3H]palmitate confirmed that it was a lipoprotein. The amino acid sequence also predicted that the mature protein contains four cysteine residues in addition to the lipid-modified cysteine of the N terminus. The existence of disulfide-bonded multimeric forms of the native immunogen was demonstrated by immunoblotting T. pallidum solubilized in the presence and absence of 2-mercaptoethanol. Triton X-114 phase partitioning of a nonlipidated form of the 17-kDa immunogen cleaved from a glutathione S-transferase fusion protein demonstrated that lipid modification is responsible for the immunogen's hydrophobic character. The same nonlipidated form of the immunogen also was used to demonstrate that lipid modification is essential for the molecule's ability to stimulate production of tumor necrosis factor alpha by murine macrophages. We conclude that covalently attached fatty acids not only anchor T. pallidum lipoproteins to spirochetal membranes but also confer upon these molecules the ability to activate immune effector cells. PMID- 8454326 TI - Requirements for invasion of epithelial cells by Actinobacillus actinomycetemcomitans. AB - Actinobacillus actinomycetemcomitans, an oral bacterium implicated in human periodontal disease, was recently demonstrated to invade cultured epithelial cells (D. H. Meyer, P. K. Sreenivasan, and P. M. Fives-Taylor, Infect. Immun. 59:2719-2726, 1991). This report characterizes the requirements for invasion of KB cells by A. actinomycetemcomitans. The roles of bacterial and host factors were investigated by using selective agents that influence specific bacterial or host cell functions. Inhibition of bacterial protein synthesis decreased invasion, suggesting the absence of a preformed pool of proteins involved in A. actinomycetemcomitans invasion. Inhibition of bacterial and eukaryotic energy synthesis also decreased invasion, confirming that A. actinomycetemcomitans invasion is an active process. Bacterial adherence to KB cells was indicated by scanning electron microscopy of infected KB cells. Further, the addition of A. actinomycetemcomitans-specific serum to the bacterial inoculum reduced invasion substantially, suggesting a role for bacterial attachment in invasion. Many of the adherent bacteria invaded the epithelial cells under optimal conditions. Inhibitors of receptor-mediated endocytosis inhibited invasion by A. actinomycetemcomitans. Like that of many facultatively intracellular bacteria, A. actinomycetemcomitans invasion was not affected by eukaryotic endosomal acidification. These are the first published observations describing the requirements for epithelial cell invasion by a periodontopathogen. They demonstrate that A. actinomycetemcomitans utilizes a mechanism similar to those used by many but not all invasive bacteria to gain entry into eukaryotic cells. PMID- 8454327 TI - Expression of gtfS is essential for normal insoluble glucan synthesis by Streptococcus downei. AB - The gtfI and gtfS genes of Streptococcus downei were investigated to determine the contribution of the respective enzymes to glucan production in the presence and absence of other glucosyltransferases. Extracts of Escherichia coli expressing cloned gtfS produced a short linear dextran from sucrose which could act as a primer for insoluble glucan synthesis when mixed with extracts of a strain expressing recombinant gtfI. To elucidate the contribution of gtfS to glucan production by S. downei, a mutant was constructed by insertionally inactivating gtfS. S. downei (gtfS mutant) colonies exhibited a marked phenotypic change on sucrose-containing media and a decreased ability to adhere to glass and produced no detectable water-insoluble glucan. These experiments confirm that expression of gtfS is essential for normal insoluble glucan synthesis by S. downei. PMID- 8454328 TI - Safety and immunogenicity in human volunteers of a chloroform-methanol residue vaccine for Q fever. AB - Current Q fever vaccines, consisting of Formalin-inactivated phase I whole Coxiella burnetii, are highly efficacious in preventing disease in high-risk settings but are associated with a risk of unacceptable local reactions in previously immune individuals and require cumbersome preliminary immunologic evaluation of potential vaccinees. A vaccine prepared from the residue of chloroform-methanol extraction of phase I Henzerling strain C. burnetii (CMR) has been shown to be less reactogenic but still immunogenic and protective in small animals and sheep. In a placebo-controlled trial, we immunized 35 healthy adults unscreened for markers of prior C. burnetii immunity with a single subcutaneous CMR dose of 30, 60, 120, or 240 micrograms. None of those receiving the 30- or 60 micrograms CMR dose and none of the placebo recipients experienced any adverse effects. Five of 15 120-micrograms dose CMR recipients complained of transient discomfort in the inoculated arm; erythema or induration of > or = 100 mm2 was noted in three and four, respectively, and two had malaise and low-grade fever (< 101 degrees F, orally). No 240-micrograms dose vaccinee reported limb discomfort, but 7 of 10 had erythema and/or induration of > or = 100 mm2 (P < 0.001 versus placebo). Two reported malaise, and one had low-grade fever. All adverse effects were self-limited. Serum immunoglobulin M responses were optimally detected with CMR antigen and occurred in 50, 60, 73, and 90% of recipients of the 30-, 60-, 120-, and 240-micrograms doses, respectively; results with phase I whole-cell antigen were similar. Serum immunoglobulin G responses were best detected with phase II antigen and were seen in 20, 20, and 40% of those receiving the 60-, 120 , and 240-micrograms doses, respectively. Peripheral blood T-cell proliferative responses to C. burnetii recall antigens were transient and of low magnitude but were seen with CMR antigen in 33% of 120-micrograms dose recipients and 40% of 240-micrograms dose recipients. Data from this study and those from comparative efficacy trials in primates should provide the basis for field trials of the CMR vaccine. PMID- 8454330 TI - Experimental hematogenous candidiasis caused by Candida krusei and Candida albicans: species differences in pathogenicity. AB - Hematogenous infections caused by Candida krusei have been noted with increasing frequency, particularly in cancer patients receiving prophylaxis with antifungal triazoles. Progress in understanding the pathogenesis of this emerging infection has been limited by the lack of an animal model. We developed a CF1 mouse intravenous inoculation model of candidiasis to evaluate the pathogenicity of C. krusei in normal and immunosuppressed mice and to compare it with that of Candida albicans. Several inocula (10(6) to 10(8) CFU per animal) of two clinical strains of C. krusei and three American Type Culture Collection strains of C. albicans were tested. Groups of 20 mice each were injected with a single intravenous dose of one inoculum. Animals randomized to receive C. krusei were immunosuppressed by intraperitoneal injection of cyclophosphamide or the combination of cyclophosphamide plus cortisone acetate or they did not receive immunosuppressive agents (normal mice). One hundred percent mortality was observed in normal mice injected with 10(6) CFU of C. albicans per mouse compared with no mortality in normal mice that received 10(8) CFU of C. krusei per mouse (P < 0.01). Resistance to C. krusei infection was markedly lowered by immunosuppression, particularly by the combination of cyclophosphamide plus cortisone acetate, with a significantly shorter survival and a higher organ fungal burden in immunosuppressed than in normal animals (P < 0.01). Tissue infection was documented by culture and histopathologic findings in all examined organs. PMID- 8454329 TI - Streptococcus mutans fructosyltransferase (ftf) and glucosyltransferase (gtfBC) operon fusion strains in continuous culture. AB - Three glucosyltransferases (GTFs), which catalyze the formation of water insoluble adherent glucans, and fructosyltransferase (FTF), which synthesizes fructans, are believed to contribute to the pathogenic potential of Streptococcus mutans. Study of the regulation of expression of GTF and FTF has been difficult because of the complexity and number of exoenzymes produced by this bacterium. By using continuous chemostat culture to control environmental conditions, chloramphenicol acetyltransferase (CAT) operon fusions were utilized to measure transcriptional activity of the ftf and gtfBC gene promoters. Expression of these operon fusions was differentially regulated in response to culture pH and growth rate and during transition states between growth domains. Furthermore, the addition of sucrose to steady-state cultures resulted in significant increases in CAT specific activities for both fusions. In a few cases, GTF and FTF enzyme specific activities did not parallel those of the corresponding CAT fusion activities; this lack of correspondence was likely due to posttranscriptional events controlling enzyme secretion and enzyme activity, as well as to the differential expression of dextranase(s) and fructan hydrolase by S. mutans. These results clearly demonstrate that the extracellular polymer synthesis machinery of S. mutans is regulated in a complex manner. The use of operon fusions in combination with chemostat culture is a viable approach to analyzing gene expression in S. mutans and will be helpful in defining the molecular mechanisms underlying regulation of expression of virulence attributes under conditions that may more closely mimic those in dental plaque. PMID- 8454331 TI - Immunochemistry of capsular type polysaccharide and virulence properties of type VI Streptococcus agalactiae (group B streptococci). AB - The immunochemistry of capsular type polysaccharide and virulence characteristics of group B streptococci (GBS), type VI, were studied. By high-pressure anion exchange chromatography and pulsed amperometric detection, as well as by 13C nuclear magnetic resonance analysis, both extracellular and cell-bound polysaccharides were found to contain glucose, galactose, and N-acetylneuraminic acid in the molar ratio of 2:2:1, respectively. At variance with all other GBS serotypes described to date (Ia, Ib, II, III, IV, and V), no N-acetylglucosamine was present, whatever the source of the material (secreted or cell bound; reference or clinical isolate). Sialic acid was probably involved in the immunodeterminant structure of this new serotype since cleavage of this sugar from the polysaccharide gave rise to an antigen which reacted very weakly with type VI antiserum and to a precipitation line in immunodiffusion with no identity with the native type VI polysaccharide. By using type VI antiserum and the protein A-gold technique, a large capsule was observed in the type VI GBS reference strain by electron microscopy. All type VI strains examined were lethal for CD-1 mice, the 50% lethal dose after intraperitoneal challenge ranging from 1.0 (+/- 0.9, standard deviation) x 10(5) to 2.5 (+/- 1.5, standard deviation) x 10(5) CFU per mouse. A rabbit antiserum against capsular type polysaccharide exhibited both protective activity for mice injected intraperitoneally with type VI reference strain or with clinical isolates and opsonic activity in a phagocytosis assay. PMID- 8454332 TI - Elevated interleukin-8 levels in the urine of patients with urinary tract infections. AB - Pyuria is one of the main features of urinary tract infections (UTI). Nevertheless, the mechanism of polymorphonuclear leukocyte (PMN) recruitment into the urine remains to be investigated. We examined whether interleukin-8 (IL-8), a potent neutrophil chemoattractant and activator, was involved in pyuria seen in UTI. Of 113 patients, 112 had elevated levels of IL-8 in their urine (1,078.0 +/- 181.5 pg/ml), regardless of whether they had an upper or lower UTI; this was in contrast to undetectable levels (less than 16 pg/ml) in the urine of all of the 20 normal individuals and 74 control patients without UTI. A concomitant study revealed increases in urine IL-6, but not IL-1 beta, and tumor necrosis factor alpha levels in patients with UTI. In addition to gram-negative bacteria, a wide spectrum of microorganisms was capable of inducing IL-8 production in urine. Local production of IL-8 in the urinary tract was suggested by a urine IL-8 level that was higher than the paired serum IL-8 level. The urine IL-8 level correlated with the number of PMN in the urine, and an average of half of the chemotactic activity in urine from patients with UTI could be abrogated by anti-IL-8 antibody treatment in vitro. Furthermore, urine IL-8 purified from patients was bioactive and showed multiple forms on immunoblotting analysis. This is the first documentation of IL-8 in the urine of patients with UTI, and these results imply that IL-8 is involved in inducing PMN migration into the urinary tract. PMID- 8454333 TI - Pneumocystis carinii organisms obtained from rats, ferrets, and mice are antigenically different. AB - Pneumocystis carinii infections were developed in animals immunosuppressed by dexamethasone treatment either from activation of latent infection (ferret) or by transtracheal inoculation with P. carinii-infected lung tissue from the homologous species (rat or mouse). Convalescent-phase antisera were obtained by stopping dexamethasone treatment after 2 to 4 weeks and allowing animals 5 to 8 weeks for recovery. P. carinii harvests from infected lungs were purified by differential filtration, solubilized in buffer containing urea, sodium dodecyl sulfate (SDS), and 2-mercaptoethanol, subjected to SDS-polyacrylamide gel electrophoresis, and blotted to polyvinylidene difluoride sheets for Western immunoblot analysis. These lung preparations are hereafter referred to as P. carinii antigens. Convalescent-phase antisera from each animal species were reacted on Western blots of P. carinii antigens prepared from organisms isolated from rats, ferrets, or mice. Each combination of P. carinii antigens and antisera from the same species of animal reacted with three or more P. carinii antigen proteins. Convalescent-phase mouse antisera reacted with P. carinii antigens from mice but not rats or ferrets. Convalescent-phase rat antisera reacted with P. carinii antigens from rats and mice but not ferrets, and convalescent-phase ferret antisera showed reactions with ferret and mouse P. carinii antigens but not rat antigens. These findings indicate antigenic differences among P. carinii strains infecting these animals. PMID- 8454334 TI - Phenotypic modulation by Legionella pneumophila upon infection of macrophages. AB - Since many pathogenic bacteria manifest a coordinate regulation of gene expression in response to different environmental stimuli, we examined the phenotypic response of Legionella pneumophila to infection of macrophage-like U937 cells. Intracellular L. pneumophila was radiolabeled, and cell extracts were subjected to two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. At least 35 Legionella proteins were selectively induced during infection of macrophages, and one of these proteins was not detected in organisms grown in vitro. Expression of at least 32 proteins was selectively repressed during infection of macrophages, and 9 of these proteins were undetectable in intracellularly grown organisms. Thirteen of the macrophage-induced proteins were also induced by one or more of several stress conditions in vitro, and two of these proteins were the heat shock GroEL- and GroES-like proteins. Nineteen of the macrophage-repressed proteins were also repressed by one or more of the stress conditions in vitro. Our data showed that intracellular L. pneumophila manifested a phenotypic modulation and a global stress response to the intracellular environment of the macrophage. The data suggested that multiple regulons are involved in this modulation, which may contribute to the survival of L. pneumophila within alveolar macrophages. PMID- 8454335 TI - Effector role of blood monocytes in experimental visceral leishmaniasis. AB - In BALB/c mice, liver granulomas provoked by visceral infection with intracellular Leishmania donovani are rapidly populated by influxing blood monocytes. To determine the host defense effector role of these mononuclear phagocytes, we treated three populations of infected animals with 5C6, an anti type 3 complement receptor monoclonal antibody (MAb), which inhibits monocyte recruitment into inflamed tissues. In naive BALB/c mice, injections of 5C6 impaired the initial acquisition of antileishmanial resistance and arrested the development of mature liver granulomas. In sensitized mice with established immunity, both resistance to rechallenge and accelerated granuloma formation were similarly inhibited by MAb administration. Finally, in naive mice, 5C6 MAb also abolished the antileishmanial activity induced by treatment with the macrophage activating lymphokine gamma interferon. Together, these results suggest a key effector role for the influxing blood monocyte in both initial and established antileishmanial defense and granuloma assembly and in the infected liver as the mononuclear phagocyte target for the antimicrobial effects of gamma interferon. PMID- 8454336 TI - Membrane damage and interleukin-1 production in murine macrophages exposed to listeriolysin O. AB - To obtain some insight into the interaction between listeriolysin O (LLO) and the macrophage membrane, we examined the effect of purified Listeria monocytogenes hemolysin on the viability and functions of mouse peritoneal exudate macrophages. The study showed that purified LLO impaired a variety of functions of the macrophages. First, it suppressed the luminol-dependent chemiluminescence response of macrophages. Second, it suppressed the phagocytic ingestion of opsonized sheep erythrocytes and latex beads. Third, exposure of macrophages to LLO resulted in an increase in dead cells, as determined by the trypan blue dye exclusion method. An interesting observation of this study is that the LLO induced production of interleukin-1 from macrophages could not be blocked by preincubation with cholesterol, while the membrane-damaging ability could be blocked by cholesterol. The dissociation of the blocking effects of cholesterol suggests that the interleukin-1-inducing ability of LLO may be distinct from its membrane-damaging ability. PMID- 8454337 TI - The major outer membrane protein of Haemophilus ducreyi is a member of the OmpA family of proteins. AB - Haemophilus ducreyi contains a major outer membrane protein (MOMP) whose apparent molecular weight is 39,000 to 42,000 for all strains tested. Two monoclonal antibodies (MAbs), designated 9D12 and 2C7, bound to the MOMP for all strains of H. ducreyi tested. As reported previously, MAb 9D12 was H. ducreyi specific (E. J. Hansen and T. A. Loftus, Infect. Immun. 44:196-198, 1984). MAb 2C7 bound to all members of the family Pasteurellaceae tested, suggesting that the MAbs bound to distinct epitopes on the MOMP. The MOMP was purified by extraction of whole cells with Zwittergent and ion-exchange chromatography. A peak eluted from a cation-exchange column contained three bands. All three species bound both MAbs, and the fraction yielded a single N-terminal amino acid sequence, suggesting that the bands represented different conformations of the MOMP. The MOMP was heat modifiable, contained two cysteine residues, and was cationic at pH 8.0, features not usually associated with classical porin proteins. The N-terminal amino acid sequence and total amino acid content of the MOMP were homologous to the OmpA proteins of members of the family Enterobacteriaceae and the OmpA-like protein of Actinobacillus actinomycetemcomitans. An OmpA-specific polyclonal serum bound to the MOMP, and MAb 2C7 bound to Haemophilus influenzae protein 5, an OmpA-like protein, indicating that the MOMP was antigenically related to OmpA. These data indicated that the most abundant protein in the outer membrane of H. ducreyi was not a classical porin and belonged to the OmpA family of proteins. PMID- 8454338 TI - Toxicity of pneumolysin to pulmonary alveolar epithelial cells. AB - Mortality during the first several days of pneumococcal pneumonia has not decreased appreciably over the past 30 years, despite the widespread use of antibiotics. Disruption of the alveolar epithelial barrier is likely an initial step in the pathogenesis of pneumococcal pneumonia. We report that soluble factors from Streptococcus pneumoniae can directly injure isolated rat alveolar epithelial cells. Using biochemical and immunological techniques, we identified pneumolysin as a major soluble S. pneumoniae toxin for alveolar epithelial cells. Alveolar epithelial cells at 24 or 72 h after isolation were equally sensitive to injury by purified pneumolysin. Purified pneumolysin substantially increased alveolar permeability in an isolated perfused rat lung model. Electron microscopy revealed that instilled pneumolysin caused widespread lung injury, primarily to type I alveolar epithelial cells. Pneumolysin toxicity to alveolar epithelial cells may be important in the pathogenesis of acute lung injury during pneumococcal pneumonia and may facilitate pneumococcal bacteremia. PMID- 8454339 TI - Association between expression of immunoglobulin G-binding proteins by group A streptococci and virulence in a mouse skin infection model. AB - In this study, we developed a mouse model of skin infection to test the association between expression of immunoglobulin-binding proteins by and infectivity of group A streptococci. Group A streptococci capable of crossing tissue barriers and establishing a lethal systemic infection in mice showed a higher level of immunoglobulin-binding protein expression. The group A streptococci recovered from the spleen of a mouse that died following a skin infection were found to be more virulent when injected into the skin of naive mice. Together, these results suggest that immunoglobulin-binding protein expression by group A streptococci correlates with their ability to establish invasive skin infections. PMID- 8454340 TI - Immunization of virgin cows with surface antigen TF1.17 of Tritrichomonas foetus. AB - Protection by surface antigen TF1.17 of Tritrichomonas foetus was investigated because it reacted with a monoclonal antibody which immobilized and mediated complement killing of the organism and prevented adherence to vaginal epithelial cells. This monoclonal antibody was used to demonstrate conservation of the antigen in most strains and to immunoaffinity purify the 50- to 70-kDa glycoprotein antigen. In preparation for immunization studies, the appropriate challenge dose of parasites was determined by intravaginal inoculation of 23 virgin cows (heifers) with 10(2), 10(4), or 10(6) live organisms at the time of estrus. More animals became infected and vaginal infection was maintained at a higher rate (P < 0.005) over 10 weeks for the group that received 10(6) organisms than in the other two groups. Therefore, this dose was used for challenge of immunized animals. Animals immunized with immunoaffinity-purified TF1.17 antigen in incomplete Freund's adjuvant or incomplete Freund's adjuvant plus dextran sulfate cleared the infection more quickly than adjuvant controls (P < 0.005). Isotype-specific enzyme-linked immunosorbent assay with T. foetus antigen showed that serum immunoglobulin G1 (IgG1) and IgG2 antibody responses as well as cervicovaginal mucus IgG1 and IgA antibodies peaked at about the time of clearance of infection in vaccinated animals. Controls developed later cervicovaginal mucus IgA antibody responses as would be expected in a primary local immune response to infection. These results indicate that vaccination with this immunoaffinity-purified surface antigen of T. foetus enhances antibody responses as well as clearance of the parasite from the female reproductive tract. PMID- 8454341 TI - Isolation and biochemical characterization of the iC3b receptor of Candida albicans. AB - In an effort to identify the protein structure on Candida albicans, pseudohyphal forms which had been shown earlier to bind human iC3b, a protein of about 42 kDa (p42), were obtained from lysates of pseudohyphal forms by absorption with C3(H2O)-Sepharose. An antiserum raised in rabbits against this protein effectively inhibited adherence of sheep erythrocytes carrying iC3b (EAC3bi) to pseudohyphal forms. p42 cross-reacted with OKM-1, a monoclonal antibody directed against the human complement receptor type 3 (CR3, CD11b). This protein, p42, was designated p42-CR3. The antiserum against p42-CR3 was used for further purification of lysates by affinity chromatography. Three proteins of 66, 55, and 42 kDa were isolated. All were recognized by OKM-1 in immunoblots (p66-, p55-, and p42-CR3). The different proteins were separated and treated with neuraminidase and endoglycosidase F. Almost complete deglycosylation of the p66 CR3 protein was obtained after treatment with neuraminidase, indicating a high degree of glycosylation. Neuraminidase also had an effect on p55-CR3, but not on p42-CR3. Endoglycosidase F did not alter any of the three proteins. In ligand blots, p42-CR3 bound C3(H2O), C3b, and iC3b but not C3d; p55-CR3 clearly reacted with C3(H2O) and weakly reacted with C3b and iC3b. p66-CR3 never showed reactivity. It is suggested that p55 and p66 represent glycosylated forms of p42 CR3. Although C. albicans CR3 and human CR3 cross-react and bind identical ligands, the two receptors differ in structure. PMID- 8454342 TI - Site-directed mutagenesis of Glu-141 and His-223 in Pseudomonas aeruginosa elastase: catalytic activity, processing, and protective activity of the elastase against Pseudomonas infection. AB - Both Pseudomonas aeruginosa elastase and Bacillus thermoproteolyticus thermolysin are zinc metalloproteases. On the basis of the high homology of the P. aeruginosa elastase with the Bacillus thermolysin, we hypothesized that Glu-141 and His-223 are the key residues for catalytic activity of the Pseudomonas elastase. To test this possibility, we replaced Glu-141 with Asp, Gln, and Gly and His-223 with Gly, Glu, and Leu by site-directed mutagenesis. These substitutions dramatically diminished the proteolytic activities of the mutant elastases when they were expressed in Escherichia coli cells. Although these mutant elastase precursors (proelastases) were produced, no appreciable processing was observed with these mutants. The possibility that autocatalysis is involved in both the processing and activation of elastase is discussed. Furthermore, by immunizing mice with vaccines made from these mutant elastase, we were able to obtain good protection against an intraperitoneal P. aeruginosa challenge. PMID- 8454343 TI - Roles of Ca2+ and F-actin in intracellular aggregation of Chlamydia trachomatis in eucaryotic cells. AB - The effect of intracellular free Ca2+ ([Ca2+]i) on the intracellular aggregation of Chlamydia trachomatis serovars L2 and E in McCoy and HeLa cells is investigated. Loading the cells with the Ca2+ chelator MAPT/AM (1,2-bis-5-methyl amino-phenoxylethane-N,N-n'-tetra-acetoxymethyl acetate), thereby decreasing the [Ca2+]i from 67 to 19 nM, decreased the number of cells with a local aggregation of chlamydiae in a dose-dependent manner. Neither the attachment nor the uptake of elementary bodies (EBs) was, however, affected after depletion of Ca2+ from the cells. There was no significant difference in the level of measured [Ca2+]i between infected and uninfected cells. Reducing the [Ca2+]i also significantly inhibited chlamydial inclusion formation. Differences in the organization of the actin filament network were observed in response to [Ca2+]i depletion. In Ca(2+) depleted cells, where few EB aggregates were formed, few local accumulations of F actin were observed in the cytosol. These results suggest that the aggregation of EBs in eucaryotic cells requires a normal homeostasis of intracellular Ca2+. By affecting F-actin reorganization and putatively certain Ca(2+)-binding proteins, [Ca2+]i plays a vital role in the infectious process of chlamydiae. PMID- 8454344 TI - Neutrophil Fc receptor participation in phagocytosis of type III group B streptococci. AB - Human peripheral blood neutrophils bear receptors for immunoglobulin G, FcRII, and FcRIII that differ structurally and functionally. We investigated the role of FcRII and FcRIII in the phagocytosis of group B streptococci (GBS) by measuring neutrophil uptake of radiolabeled type III GBS. The mean uptake of GBS opsonized with human serum containing complement and specific antibody was 76%, but when this serum was heated, the mean uptake was only 22%. A monoclonal antibody to FcRIII, Leu-11b, inhibited in a dose-dependent manner uptake of GBS opsonized with heated or intact serum to maxima of 40 and 30%, respectively. Conversely, a monoclonal antibody to FcRII, IV.3, inhibited by 77% the uptake of GBS opsonized with heated serum but had no effect when GBS was opsonized with intact serum. Leu 11b and IV.3 had an additive inhibitory effect with heated but not with intact serum. Neither monoclonal antibody inhibited the uptake of GBS opsonized with hypogammaglobulinemic serum. Therefore, FcRII is the primary mediator of the phagocytosis of GBS opsonized by antibody alone, whereas FcRIII plays a lesser role. Surprisingly, FcRII is not necessary for phagocytosis when complement is also present. FcRIII participates, to a limited extent, in phagocytosis of GBS opsonized with antibody whether or not complement is present. These findings suggest that the function of FcRII in triggering phagocytosis may be particularly important in host defense against type III GBS in the setting of complement deficiency of young infants. PMID- 8454345 TI - Restricted ability of group B streptococcal C5a-ase to inactivate C5a prepared from different animal species. AB - Most strains of group B streptococci (GBS) elaborate a cell surface-associated enzyme that rapidly inactivates the human complement-derived chemoattractants C5a and C5adesarg by cleaving the His-Lys bond at positions 67 and 68 in the C5a molecule. We have suggested that rapid inactivation of C5a and C5adesarg by this enzyme, called C5a-ase, can hinder the inflammatory response at sites of GBS infection. We tested the ability of GBS C5a-ase to inactivate C5a preparations from various animal species to determine the proper species for studying the role of GBS C5a-ase in the pathogenesis of GBS infections. Exposure of C5a preparations from humans, monkeys, and cows to GBS caused inhibition of C5a functional activity as measured by the ability of C5a to stimulate human polymorphonuclear leukocyte (PMN) adherence and human PMN chemotaxis. Bovine PMN chemotaxis to bovine C5a was also abolished after exposure of bovine C5a to GBS. In contrast, mouse, rat, guinea pig, rabbit, pig, and sheep C5a preparations retained full functional activity after exposure to GBS as measured by chemotaxis of human PMNs, PMNs from the same animal species, or both. These data suggest that there are structural differences between C5a proteins from different species which alter their susceptibility to GBS C5a-ase and indicate that most commonly used animal models of human GBS infection are inadequate for detection of a contribution of GBS C5a-ase to GBS virulence. PMID- 8454346 TI - Effects of ATPase inhibitors on the response of HeLa cells to Helicobacter pylori vacuolating toxin. AB - Approximately 50% of Helicobacter pylori strains produce a toxin in vitro that induces vacuolation of eukaryotic cells. To determine whether ion transport pathways are important in the formation of toxin-induced vacuoles, HeLa cells were incubated with H. pylori toxin in the presence of nine different inhibitors of ion-transporting ATPases. Oligomycin, an inhibitor of predominantly F1F0-type ATPases, had no effect on toxin activity. Inhibitors of predominantly V-type ATPases, exemplified by bafilomycin A1, inhibited the formation of vacuoles in response to the H. pylori toxin and reversed the vacuolation induced by the toxin. In contrast, at concentrations of > or = 100 nM, ouabain and digoxin, inhibitors of the Na(+)-K+ ATPase, potentiated the activity of H. pylori toxin. The inhibitory effects of bafilomycin A1 could not be overcome by the potentiating effects of ouabain. These data suggest that intact activity of the vacuolar ATPase of eukaryotic cells is a critical requirement in the pathogenesis of cell vacuolation induced by H. pylori toxin and that vacuole formation by this toxin is associated with altered cation transport within eukaryotic cells. PMID- 8454347 TI - Eicosanoid production by mouse peritoneal macrophages during Toxoplasma gondii penetration: role of parasite and host cell phospholipases. AB - The metabolism of endogenous arachidonic acid by mouse resident peritoneal macrophages infected in vitro with Toxoplasma gondii was studied. Prelabeling of macrophages with [5,6,8,9,11,12,14,15-3H]arachidonic acid and challenge with tachyzoites for 15 min resulted in a high mobilization of free labeled arachidonic acid (178%) in the culture medium. The parasites also triggered the synthesis of 6-keto-prostaglandin F1 alpha (47%), prostaglandin E2 (44%), leukotrienes C4 and D4 (33%) and 5-, 12-hydroxyeicosatetraenoic acids (155%). The study indicated that during the intracellular development phase of the parasites, 6-keto-prostaglandin F1 alpha (38%), prostaglandin E2 (31%) leukotrienes C4 and D4 (15%), hydroxyeicosatetraenoic acids (43%), and free arachidonic acid (110%) were secreted into the culture medium. Pretreatment of tachyzoites with phospholipase A2 inhibitors (4-p-bromophenacyl bromide and quinacrine) and no calcium in the culture medium resulted in inhibition of tachyzoite penetration into the macrophages and a decrease of the arachidonic acid metabolism. The triggering of the arachidonic acid cascade by T. gondii was dependent on the active penetration of the parasites into the macrophages, whereas preincubation of the macrophages with phospholipase A2 inhibitors did not affect penetration or free arachidonic acid release, thereby supporting a role for parasite phospholipase in the penetration process and in arachidonic acid mobilization from macrophage membrane phospholipids. Moreover, treatment of macrophages with phospholipase A2 inhibitors decreased the activities of the cyclooxygenase and lipoxygenase pathways, also suggesting an activation of host cell phospholipase A2 by the parasite. PMID- 8454348 TI - Superoxide dismutase and the resistance of Escherichia coli to phagocytic killing by human neutrophils. AB - Transformation of Escherichia coli K-12-derived strains with a plasmid carrying the genetic determinants for synthesis of lipopolysaccharide O antigen by Shigella dysenteriae allows the construction of phenotypically smooth derivatives. We show that such E. coli K-12 derivatives are highly resistant to killing by human serum. Isogenic wild-type and sodB mutant (Fe superoxide dismutase-deficient) strains were constructed. The results of experiments on phagocytic killing of these strains by human neutrophils are reported. We observed no difference between the sensitivities of wild-type and sodB mutant strains to phagocytic killing, in contrast to the results reported by other researchers who used species other than E. coli or strains other than K-12. PMID- 8454349 TI - Long-lived respiratory immune response to filamentous hemagglutinin following Bordetella pertussis infection. AB - Systemic and mucosal B-cell-mediated immune responses to purified filamentous hemagglutinin (FHA) in mice were analyzed at different times following a single respiratory infection with Bordetella pertussis. Serum immunoglobulin G (IgG) anti-FHA and respiratory IgG and IgA anti-FHA antibodies were first detected at 3 weeks postinfection, reached high levels by 8 weeks postinfection, and remained at high levels 12 to 32 weeks postinfection. FHA-specific B lymphocytes isolated from the spleens or lungs of uninfected control mice or mice convalescing from B. pertussis respiratory infection were analyzed in limiting-dilution cultures. Analysis of culture supernatants for the production of antibodies to FHA revealed an increased frequency of FHA-specific B cells of both the IgG- and the IgA secreting classes in the lungs and tracheas of aerosol-challenged mice; these levels remained high as late as 25 weeks postinfection, compared with those in uninfected controls. No corresponding increase in the frequency of FHA-specific B cells in the spleens of aerosol-infected mice was observed. This long-lasting response observed in cultured cells was radiation resistant, a result suggesting that this response was due to B cells already activated in vivo. Polymerase chain reaction analysis revealed low but detectable levels of B. pertussis chromosomal DNA in 75% of mice tested at 8 weeks postinfection and 37.5% of mice tested at 26 weeks postinfection, at which times high levels of anti-FHA antibody were detected. One explanation for these data may be that, in this animal model, a major adhesin of B. pertussis can persist and interact with components of the immune system to stimulate the production of specific antibody in the respiratory tract many weeks after a single B. pertussis infection. PMID- 8454350 TI - Specific and nonspecific responses of murine B cells to membrane blebs of Borrelia burgdorferi. AB - Lymphocyte blastogenesis assays and immunoblotting were used to investigate and compare murine B-cell responses to preparations of extracellular membrane blebs (BAg) and spirochetes (Ag) of Borrelia burgdorferi. Immunoblotting BAg, Ag, and medium control preparations with serum from naive and infected C57BL/10 mice revealed that BAg and Ag had similar specific reactivity profiles except that major antigens of 83, 60, and 41 kDa were detected in Ag but not in BAg. It was determined that 1 microgram (dry weight) of Ag contained 0.0051 and 0.0063 microgram of outer surface proteins A (OspA) and OspB, respectively, whereas 1 microgram (dry weight) of BAg contained 0.0024 microgram of OspA and 0.0015 microgram of OspB. Both BAg and Ag caused blastogenesis in cultures of spleen cells from both groups of mice, but BAg-stimulated lymphocytes exhibited significantly greater (P < or = 0.05) blastogenesis after 2 or 6 days of culture than did lymphocytes stimulated by Ag or medium control. Flow cytometry and antibody capture enzyme-linked immunosorbent assays identified responding lymphocytes as B cells which secreted polyclonal immunoglobulin M (IgM) but not IgG or IgA. Treatment of BAg and lipopolysaccharide controls with polymyxin B resulted in as much as 20.7 and 54.3% mean decreases in blastogenesis, respectively. Fractionation of BAg or Ag by ultracentrifugation before culture with spleen cells from naive mice indicated that B-cell blastogenesis was probably associated with spirochetal membranes. The results of this study demonstrate that specific humoral responses are directed towards extracellular membrane blebs which lack the 83-, 60-, and 41-kDa antigens of intact spirochetes and that blebs also possess significant nonspecific mitogenic activity for murine B cells. This activity was not due entirely to typical lipopolysaccharide or OspA and OspB lipoproteins. PMID- 8454351 TI - Gamma interferon cooperates with lipopolysaccharide to activate mouse splenic macrophages to an antihistoplasma state. AB - Inhibition of the intracellular growth of Histoplasma capsulatum by murine resident red pulp splenic macrophages was examined. Splenic macrophages, unlike resident peritoneal macrophages, required a prolonged preincubation (18 h) with recombinant murine gamma interferon (rMuIFN-gamma) for activation. To be fully activated, the splenic macrophages required incubation with rMuIFN-gamma in combination with 0.1 microgram of lipopolysaccharide (LPS) per ml. Splenic macrophages stimulated with rMuIFN-gamma, LPS, or rMuIFN-gamma and LPS produced tumor necrosis factor alpha (TNF-alpha), but recombinant murine TNF-alpha (rMuTNF alpha) did not activate macrophages when used alone or as a second signal with rMuIFN-gamma. Anti-TNF-alpha antibody did not block IFN-gamma-LPS activation of splenic macrophages to any significant extent. One hundred micromolar ferrous sulfate antagonized IFN-gamma-LPS activation of splenic macrophages, indicating that iron was involved in the fungistatic activity of cytokine-stimulated phagocytes. Our results indicate that (i) splenic macrophages differ significantly from peritoneal macrophages in their requirements for activation and (ii) the mechanism by which splenic macrophages exert their antifungal effects involves iron. PMID- 8454352 TI - Complement component C5 modulates the systemic tumor necrosis factor response in murine endotoxic shock. AB - Patients with disseminated Neisseria meningitidis infections (meningococcemia) suffer from a fulminant shock syndrome that is accompanied by extraordinarily high concentrations in serum of tumor necrosis factor (TNF). People with homozygous deficiencies of late complement components (C5, C6, C7, and C8) experience a high incidence of disseminated neisserial infections yet suffer from an attenuated form of the disease. The mechanisms that account for this disparity in host response are unclear, but they may in part be related to differences in the systemic TNF response that are modulated by terminal complement components (C5 to C9). The role of C5 in the modulation of the systemic endotoxin-induced TNF response was studied with matched strains of C5-deficient (B10 D2/Osn) and complement-sufficient (B10 D2/Nsn) mice. Following lipopolysaccharide (LPS) administration, complement-sufficient mice exhibited more rapid increases in pulmonary and hepatic vascular permeabilities than did C5-deficient controls. Complement-sufficient mice developed acute passive hepatic congestion, they appeared more ill than C5-deficient mice, and they exhibited a twofold greater rise in serum TNF activity compared with that by C5-deficient mice. C5-deficient mice reconstituted with normal serum before an LPS injection exhibited pulmonary and hepatic vascular permeability increases and serum TNF levels approaching those observed in complement-sufficient mice. Alveolar and peritoneal macrophages isolated from complement-sufficient and C5-deficient mice and incubated in heat inactivated serum did not exhibit differences in TNF mRNA expression or secreted TNF activity following stimulation with LPS. However, incubation of macrophages in complement-sufficient mouse serum (before LPS stimulation) resulted in increased TNF mRNA expression and TNF activity compared with those in cells incubated in C5-deficient serum. In vitro studies employing human complement components and peripheral blood monocytes revealed that recombinant C5a, in the presence or absence of LPS, can induce increased concentrations of TNF and that C5b to C9 had no additional modulatory effect on the TNF response. These data suggest that C5 modulates the endotoxin-triggered TNF response. The role of complement components distal to C5 (i.e., C5b to C9) in the endotoxin-triggered TNF response remains unclear. PMID- 8454353 TI - Complete development of Cryptosporidium parvum in a human endometrial carcinoma cell line. AB - Sporozoites of Cryptosporidium parvum, excysted from oocysts isolated from calves, were applied to monolayers of the human endometrial carcinoma cell line RL95-2. Cells were grown as monolayers in 24-well plates at concentrations ranging from 5 x 10(4) to 1 x 10(5) RL95-2 cells per well. At 1 or 7 days postculturing, C. parvum sporozoites (ranging from 1 x 10(5) to 2 x 10(5) were added to the monolayers of RL95-2 cells. The cells were fixed and stained to estimate the extent of parasite colonization. Light microscopy and electron microscopy confirmed the development and replication of C. parvum within the RL95 2 cells. A standardized and reproducible in vitro culture system for C. parvum is necessary to evaluate therapies against cryptosporidiosis. PMID- 8454354 TI - Tick salivary gland extract and interleukin-2 stimulation enhance susceptibility of lymphocytes to infection by Theileria parva sporozoites. AB - Intracellular parasites show host cell specificity, and precise information on the range of host cells is a prerequisite for the identification of host molecules that account for the specificity and are involved in entry processes. The sporozoite stage of the tick-borne protozoan parasite Theileria parva binds to and enters bovine lymphocytes, but precise information on the susceptibility of other cell types present at the tick attachment site is unavailable. We quantitatively examined the susceptibility of cell types known to be present at the tick attachment site by a previously established in vitro assay. Apart from lymphocytes, sporozoites also bind to and enter macrophages and afferent lymph veiled cells; they do not bind to or enter fibroblasts, granulocytes, or erythrocytes. Sporozoites are not phagocytosed by the macrophages or veiled cells but enter them as they do lymphocytes. Since the tick attachment site is a region of cellular inflammation, we also examined the effects of agents known to be present in this area on lymphocyte susceptibility. Short-term preincubation of lymphocytes with tick salivary gland extract, with compounds that induce lymphocyte proliferation, or with interleukin-2 (IL-2), a cytokine produced by activated lymphocytes, increased host cell susceptibility by between 30 and 60%. The IL-2-induced increase in host cell susceptibility could be prevented by treating the lymphocytes with the monoclonal antibody IL-A 111, which reacts with the bovine IL-2 receptor alpha chain and inhibits IL-2-driven cell proliferation. The changes induced by tick salivary gland extract and IL-2 occurred in less than 90 min. Similarly, peripheral blood mononuclear cells from an animal previously immunized with a nonrelated antigen (trypanosome variant surface glycoprotein) and stimulated in vitro with the same antigen showed increases in host cell susceptibility of between 70 and 125%. In contrast, treatment of lymphocytes with gamma interferon did not induce any increase in host cell susceptibility. PMID- 8454355 TI - Protective role of interleukin 6 in the lipopolysaccharide-galactosamine septic shock model. AB - C57BL/6J mice given low doses of lipopolysaccharide (LPS) (100 ng per mouse) plus D-galactosamine (8 mg per mouse) die within 24 h following LPS administration. We used this septic shock model to confirm the role of tumor necrosis factor in mortality using a monoclonal antibody to tumor necrosis factor to prevent lethality. Furthermore, we demonstrated that interleukin 6, rather than playing a lethal role, protected mice against death in this septic shock model. Antibody to interleukin 6 did not affect the fatal outcome in this low-LPS-dose model. However, pretreatment with antibody to tumor necrosis factor did protect the mice against death, in a dose-dependent manner. Moreover, mortality was enhanced by pretreatment with antibody to interleukin 6 when tumor necrosis factor was partly limited by anti-tumor necrosis factor treatment. Mortality was significantly reduced by pretreatment with both recombinant interleukin 6 and low doses of antibody to tumor necrosis factor; in the absence of the low dose of antibody to tumor necrosis factor, interleukin 6 alone did not confer any protection. These data demonstrate in vivo antagonistic activities of tumor necrosis factor and interleukin 6 and show that interleukin 6 can play a protective role against death from septic shock. PMID- 8454356 TI - Filamentous growth and elevated vaginopathic potential of a nongerminative variant of Candida albicans expressing low virulence in systemic infection. AB - The vaginopathic potential and the intravaginal morphology of a nongerminative variant of Candida albicans, strain CA-2, were studied in a rat vaginitis model. Although it expressed low virulence in systemic infections, strain CA-2 was capable of causing a vaginal infection of the same duration and extent as that obtained in rats challenged with the germ-tube-forming strain C. albicans 3153 from the stock collection or with a fresh clinical isolate of C. albicans from a case of human vaginitis. During the experimental infection, the CA-2 cells did not maintain their yeast morphology but gave rise to single enlarged-elongated elements (1 to 2 days) which grew predominantly as coarse, short, pseudomycelium like filaments (2 to 3 days) and then as long threads (7 days). These latter filaments were ultimately indistinguishable from the hyphal filaments formed by the germ-tube-forming strains, which, however, initially developed in the vagina by typical germ tube formation. This peculiar morphological development of strain CA-2 was not observed in organs of systemically infected mice, where, in contrast to strain 3153 which formed typical hyphae, strain CA-2 maintained a typical pattern of yeast growth. Vaginal isolates of strain CA-2 taken at different days of infection were found to be identical to the challenging CA-2 cells, in terms of biochemical characteristics, inability to form germ tubes in any medium at 37 degrees C in vitro, echinocandin resistance, DNA biotype, and low virulence in systemic infections in mice. Thus, experimental vaginitis by strain CA-2 is associated with a peculiar filamentous growth in the vagina, through an apparently novel morphological development bypassing classical germ tube formation but ultimately leading to ordinary hyphae. The elevated vaginopathic potential of strain CA-2, in contrast to its low virulence in systemic infection, also suggests that different Candida virulence factors (and host responses) come into play in local and disseminated candidal infections. PMID- 8454357 TI - Homologs of Mycobacterium leprae 18-kilodalton and Mycobacterium tuberculosis 19 kilodalton antigens in other mycobacteria. AB - Most of the antigens of Mycobacterium leprae and M. tuberculosis that have been identified are members of stress protein families, which are highly conserved throughout many diverse species. Of the M. leprae and M. tuberculosis antigens identified by monoclonal antibodies, all except the 18-kDa M. leprae antigen and the 19-kDa M. tuberculosis antigen are strongly cross-reaction between these two species and are coded within very similar genes. Studies of T cell reactivity against mycobacterial antigens have indicated that M. tuberculosis bears epitopes that are cross-reactive with the M. leprae 18-kDa antigen, but attempts to identify an 18-kDa antigen-like protein or protein coding sequence in M. tuberculosis have been unsuccessful. We have used a combination of low-stringency DNA hybridization and polymerase chain reaction techniques to identify, isolate, and sequence genes from M. avium and M. intracellulare that are very similar to the 18-kDa antigen gene of M. leprae and others that are homologs of the 19-kDa antigen gene of M. tuberculosis. Unlike M. leprae, which contains a single 18-kDa antigen gene, M. avium and M. intracellulare each have two 18-kDa antigen coding sequences. Although the M. leprae, M. avium, and M. intracellulare 18-kDa antigen genes are all very similar to one another, as are the M. tuberculosis, M. avium, and M. intracellulare 19-kDa antigen genes, we have been unable to detect any 18 kDa antigen-like coding sequences in DNA from M. tuberculosis. PMID- 8454358 TI - The immunodominant 90-kilodalton protein is localized on the terminal tip structure of Mycoplasma pneumoniae. AB - Immunoblot analysis of convalescent-phase sera of experimentally infected chimpanzees or monoclonal antibodies (MAbs) specific to the 90- and 40-kDa proteins of Mycoplasma pneumoniae indicated that both proteins were present in cytadsorbing, pathogenic strains PI-1428, M129, and FH but absent in noncytadsorbing, nonpathogenic strain M129-B176. Adsorption of convalescent-phase chimpanzee sera with virulent strain PI-1428 removed reactivity, whereas adsorption with avirulent strain M129-B176 did not remove reactivity to these two proteins. By using proteolysis and specific MAbs, we demonstrated that the 90- and 40-kDa proteins were surface exposed. Immunoelectron microscopy employing specific MAbs showed that the 90-kDa protein is localized on the terminal tip attachment apparatus. However, the MAb specific for the 40-kDa protein failed to indicate a similar localization. Nevertheless, these data, taken together, indicate that the immunodominant 90- and 40-kDa proteins are surface exposed, are localized on the terminal tip apparatus, and might be involved in the attachment mechanism. PMID- 8454359 TI - Antibodies to Haemophilus influenzae type b outer membrane proteins in children with epiglottitis or meningitis and in healthy controls. AB - The two most common manifestations of Haemophilus influenzae type b (Hib) infection in Western communities are meningitis and epiglottitis. The role of antibodies against outer membrane proteins (OMP) in the pathogenesis of these diseases was investigated by Western blotting (immunoblotting) with an OMP antigen prepared from a local Hib strain. Acute- and convalescent-phase serum samples from 25 children with epiglottitis and 20 with meningitis and single serum samples from 19 control children in the same age group were tested. Western blots were evaluated quantitatively by use of graphs generated from a densitometer. OMP antibody was detected in all sera from patients and controls. There was no significant difference between the mean antibody level in acute phase sera from children with meningitis (336 +/- 143 arbitrary units) and those from children with epiglottitis (286 +/- 134 arbitrary units). However, the mean OMP antibody level in sera from healthy controls, with no known history of Hib disease, was significantly higher than that in sera from patients with Hib disease within 2 days of admission to the hospital (patients [n = 35], 282 +/- 144; controls [n = 19], 425 +/- 236; P = 0.007). The difference was due mainly to higher levels, in control sera, of antibody against four proteins, one of which is either P1 or a comigrating protein of 49 kDa. The finding of higher levels of OMP antibody in healthy controls suggests a protective role for antibodies directed against one or more OMP. This information could be exploited in future vaccine development. PMID- 8454360 TI - The cell wall mediates pneumococcal attachment to and cytopathology in human endothelial cells. AB - Streptococcus pneumoniae interacts with vascular endothelial cells during the course of bacteremia. In this study, we characterized the initial attachment of pneumococci to human endothelial cells (EC) and the response of the endothelium to this interaction. Pneumococci adhered to EC in a dose-dependent fashion. Attachment was rapid, with the majority of bacteria attached by 30 min. No difference was found between the attachment of unencapsulated (R6) and encapsulated (SIII) strains. Purified pneumococcal cell wall components competitively inhibited attachment of R6 by a maximum of 60% in a dose-dependent manner. Following attachment of pneumococci or exposure of EC to pneumococcal cell wall, pronounced changes in EC morphology ensued, resulting in striking separation of the cells of the monolayer and, eventually, destruction of the cells. The cytopathic effects of the cell wall were inhibited by antibodies to interleukin-1 but not to tumor necrosis factor. Both antibodies were required to neutralize the cytopathology caused by intact pneumococci. We conclude that pneumococci attach rapidly to human EC and that the cell wall is important in this interaction. Intact pneumococci and pneumococcal cell wall induce profound morphologic changes in human EC, leading to loss of barrier integrity. These cytopathic effects are likely to be cytokine mediated. PMID- 8454361 TI - Prolonged inhibition of bacterial protein synthesis abolishes Salmonella invasion. AB - We have found that prolonged inhibition of bacterial protein synthesis abolishes the ability of Salmonella typhimurium to enter HEp-2 cells. Our results suggest that an essential invasion factor has a functional half-life that is seen as a gradual loss of invasiveness in the absence of protein synthesis. Therefore, Salmonella invasiveness appears to be a transient phenotype that is lost unless protein synthesis is maintained. This finding may explain why salmonellae grown to stationary phase lose their ability to enter cultured cells. In addition, a short-lived capacity to enter cells may be important during infection so that bacterial invasiveness is limited to certain times and host sites during pathogenesis. PMID- 8454362 TI - Identification of a salivary agglutinin-binding domain within cell surface adhesin P1 of Streptococcus mutans. AB - DNA encoding the alanine-rich region (A-region) of the cell surface adhesin, P1, from Streptococcus mutans was subcloned and expressed as a fusion protein with the maltose-binding protein (MBP) of Escherichia coli. The A-region fusion protein was shown to competitively inhibit both adherence of S. mutans to salivary agglutinin-coated hydroxyapatite and fluid-phase agglutinin-mediated aggregation of this organism. MBP alone or an MBP-paramyosin fusion protein was not inhibitory. Proteolytic cleavage of the fusion protein into its component moieties, MBP and A-region, resulted in breakdown of the A-region into three main fragments. Western immunoblot analysis of calcium-dependent agglutinin binding to this preparation revealed binding specificity for a 28-kDa fragment. Thus, the A region of P1 is an important domain which interacts directly with salivary agglutinin, and this interaction interferes with both the aggregation and the adherence mechanisms in vitro. PMID- 8454363 TI - Comparison of receptors required for entry of Leishmania major amastigotes into macrophages. AB - We investigated the mechanisms of entry of amastigotes of Leishmania major from two different sources into macrophages by comparing their use of the Fc receptor (FcR), complement receptor type 3 (CR3), and mannose-fucose receptor (MFR). Amastigotes were obtained from BALB/c mice and SCID mice. FcR involvement was examined by opsonizing L. major with parasite-specific immunoglobulin G (IgG). Antiparasite IgG did not alter the uptake of amastigotes from BALB/c mice since these amastigotes had antibody bound to their surface: IgG1 was the most predominant antibody, followed by IgG2b, IgM, and IgG2a. However, opsonization with antiparasite IgG enhanced the entry of amastigotes that lacked antibody on their surface, namely, amastigotes obtained from SCID mice or from macrophages infected in vitro. These results indicate that the FcR is important for amastigote entry into macrophages. Down-modulation of FcRs onto immune complexes, however, did not reduce the entry of amastigotes containing surface-bound IgG into macrophages. Monoclonal antibodies against the CR3 inhibited the entry of amastigotes from either BALB/c or SCID mice into J774A.1 macrophage-like cells. Simultaneous blocking of FcR and CR3 further increased the inhibition of phagocytosis. Treatment of macrophages with soluble mannan or down-modulating the MFR onto mannan-coated coverslips had no effect on the entry of amastigotes from BALB/c or SCID mice. Thus, the MFR does not appear to be used by amastigotes of L. major. We show that ingestion of amastigotes appears to occur primarily through the FcR and CR3; however, additional receptors may also participate in the uptake of amastigotes. PMID- 8454364 TI - Cloning and sequence analysis of the structural pilin gene of Brazilian purpuric fever-associated Haemophilus influenzae biogroup aegyptius. AB - We have cloned and sequenced the Brazilian purpuric fever (BPF)-associated Haemophilus influenzae biogroup aegyptius (Hae) pilin gene. The sequence contained a 648-bp open reading frame encoding a mature pilin protein of 191 amino acids with a calculated mass of 20.5 kDa. There was 82% homology between the open reading frames of the BPF strain F3031 and H. influenzae type b (Hib) (strain M43) pilin genes and 71% homology at the amino acid level between the mature pilin proteins. However, areas of diversity were noted throughout the gene. A 17-bp probe corresponding to an area of diversity in the N-terminal region of the BPF-associated gene hybridized with other BPF strains but not with non-BPF Hae or Hib. In summary, the pilin protein of BPF-associated Hae is highly homologous to Hib pilin yet remains structurally distinct. PMID- 8454365 TI - Analysis of a DNA polymorphic region in the gtfB and gtfC genes of Streptococcus mutans. AB - We have previously demonstrated the existence of DNA polymorphisms at the 5' coding regions of the gtfB and gtfC genes specifying the streptococcal glucosyltransferases (J.S. Chia, T.Y. Hsu, L.J. Teng, J.Y. Chen, L.J. Hahn, and C.S. Yang, Infect. Immun. 59:1656-1660, 1991). DNA sequence analysis by polymerase chain reaction and direct sequencing revealed that while several nucleotide changes were identified, accounting for the polymorphisms, the amino acids which they code for remain unchanged. The polymorphic region is located in a highly conserved amino terminus of the glucosyltransferases. A peptide of 19 amino acids from this region reversed the inhibiting activity of an antiserum raised against the proteins coded for by the gtfB and gtfC genes. The results suggest that the polymorphic region, varying in DNA but not in amino acid sequences, might specify some biological function. PMID- 8454366 TI - Localization of the virulence-associated genes pilA, pilR, rpoN, fliA, fliC, ent, and fbp on the physical map of Pseudomonas aeruginosa PAO1 by pulsed-field electrophoresis. AB - Seven virulence-associated genes have been placed on a genomic map of Pseudomonas aeruginosa PAO1, using pulsed-field electrophoresis, on the basis of the previous physical maps of Romling et al. (U. Romling, M. Duchene, D. Essar, D. Galloway, C. Guidi-Rontani, D. Hill, A. Lazdunski, R. Miller, K. Schleifer, D. Smith, H. Toschka, and B. Tummler, J. Bacteriol. 174:327-330, 1992; U. Romling, D. Grothues, W. Bautsch, and B. Tummler, EMBO J. 8:4081-4089, 1989) and Ratnaningsih et al. (E. Ratnaningsih, S. Dharmsthiti, V. Krishnapillai, A. Morgan, M. Sinclair, and B. W. Holloway, J. Gen. Microbiol. 136:2351-2357, 1990). The new locations for the outer membrane enterobactin iron-siderophore receptor ent gene (41 to 42 min) and the fliA gene (59 to 61 min), which encodes a minor sigma factor of RNA polymerase, are given. The pilA (the pilin structural gene), pilR (a pilin regulatory gene), and rpoN (encoding another minor sigma factor of RNA polymerase) genes map together at 71 to 75 min, locations correcting the previously reported values (V. Shortridge, M. Pato, A. Vasil, and M. Vasil, Infect. Immun. 59:3596-3603, 1990). The fbp gene (28 to 29 min), which encodes an outer membrane ferripyochelin-binding protein of low molecular weight, and the fliC gene (64 to 66 min), the flagellin structural gene, were determined to lie in the previously reported locations. PMID- 8454367 TI - High sodium chloride concentrations inhibit staphylococcal enterotoxin C gene (sec) expression at the level of sec mRNA. AB - Expression of the staphylococcal enterotoxin type C gene (sec) is regulated in response to both high NaCl concentrations (osmolarity) and the accessory gene regulator (agr). agr is a global regulator that alters the expression of many genes in Staphylococcus aureus. In this report, we have demonstrated that osmoregulation of sec occurs at the level of mRNA independently of an intact agr allele. Northern (RNA) and Western blot (immunoblot) analyses of samples from cultures grown in low- (0 M NaCl) and high-osmotic-strength (1.2 M NaCl) media revealed that the low-osmotic-strength culture contained approximately 16-fold more SEC and sec mRNA than the high-osmotic-strength culture. sec expression in high-osmotic-strength medium was enhanced when osmoprotective compounds were added. Osmoregulation of sec expression in Agr- strains was also examined; SEC and sec mRNA levels decreased in response to high osmolarity in a manner similar to that seen in the Agr+ strains. PMID- 8454368 TI - Exacerbation of Pneumocystis carinii pneumonia in immunodeficient (scid) mice by concurrent infection with a pneumovirus. AB - scid mice naturally infected with Pneumocystis carinii and inoculated with a normally apathogenic pneumovirus had significantly higher P. carinii cyst counts and developed significantly more severe P. carinii-related disease than did sham inoculated, P. carinii-infected scid mice. P. carinii-free, virus-infected scid mice survived for 2 months despite high pulmonary virus titers. These results show that a respiratory virus infection can exacerbate P. carinii disease in an immunocompromised-rodent model. PMID- 8454369 TI - Neutralizing antibodies to Haemophilus ducreyi cytotoxin. AB - Neutralizing antibodies against cytotoxin produced by Haemophilus ducreyi bacteria were studied in rabbits by an assay employing HEp-2 cells and diluted crude cytotoxin preparations from the organism. Antisera to 12 different H. ducreyi strains were prepared by immunization of rabbits with bacterial sonicates combined with Freund's adjuvant. The antibody response during infection with H. ducreyi was studied in two groups of rabbits which were infected with five live strains by either single or multiple intradermal injections. Neutralizing antibodies in hyperimmune sera to sonicates from 12 H. ducreyi strains tested against their homologous cytotoxin preparations were present with titers ranging from 1:80 to 1:640. Similar antibody titers against heterologous cytotoxin preparations were recorded, indicating immunological similarity or identity between cytotoxins from the various H. ducreyi strains. Three strains did not produce cytotoxin, and these strains did not induce toxin-neutralizing antibodies. Hyperimmune sera to other gram-negative bacteria had no detectable neutralizing capacity, indicating species specificity of the H. ducreyi cytotoxin. Cytotoxin-neutralizing antibodies were not detectable in rabbit sera before infection with H. ducreyi. Repeated single injections with live bacteria resulted in development of low levels of neutralizing antibodies. Multiple primary injection of live bacteria of the cytotoxin-producing strain CCUG 7470 resulted in a low immune response to the cytotoxin preparation from the same strain. A booster infection resulted in the development of neutralizing antibodies in all rabbits infected with cytotoxin-producing strains. The antibody titers determined against the homologous cytotoxin preparation were similar to those recorded for two heterologous cytotoxin preparations. PMID- 8454370 TI - Reduction of bacterial titers by low-dose aspirin in experimental aortic valve endocarditis. AB - Using a rabbit model of Staphylococcus aureus endocarditis, we studied the effects of aspirin on the natural progression of this infection. Compared with untreated animals, the aspirin-treated animals showed a 30% (P = 0.11) reduction in the weight of the vegetations and an 84% (P = 0.03) reduction in the bacterial titer of the vegetations. PMID- 8454371 TI - Interaction between human immunodeficiency virus and Toxoplasma gondii replication in dually infected monocytoid cells. AB - THP-1 monocytoid cells, either not infected or chronically infected with human immunodeficiency virus type 1 (HIV-1), were challenged with Toxoplasma gondii. Parasitic growth, as assessed by trophozoite counting and measurement of supernatant p30 membrane antigen, was similar in HIV-infected and noninfected THP 1 cells. Also, T. gondii did not affect HIV replication. These experiments therefore failed to demonstrate any interaction between HIV-1 and T. gondii replication in concurrently infected monocytoid cells. PMID- 8454372 TI - Cardiovascular damage from smoking: a fact or belief? AB - A large series of epidemiological, clinical and pathological studies relate cigarette smoking to the development of cardiac damage. Both active and passive smoking seen to act negatively on the heart causing atherosclerotic coronary alterations, focal myocardial lesions and arrhythmias. Acute exposure to passive smoking impairs cardiac performance in healthy people and subjects who survived a first acute myocardial infarction. Several variables, which are due to type of smoking, subject and environment, may interfere with experimental results. When we standardize these variables, cardiac damage caused by cigarette smoking is an undoubted fact. PMID- 8454373 TI - Characteristics and mechanisms of tachyphylaxis of cardiac contractile response to insulin. AB - Although insulin is known to cause internalization of its own receptors, the physiological significance of this phenomenon is not clear. In the isolated rat heart we observed that the positive inotropic effect of 25 munits/ml insulin was completely abolished if the heart was preperfused with insulin for 10 min. This tachyphylactic response to insulin began to appear 3-4 min after starting preperfusion with insulin and was partially reversible after 30 min of washing. Preperfusion with insulin did not affect the action of vanadate, which has insulin-like effect on glucose transport, or the actions of the other positive inotropic agents, isoproterenol and ouabain. The presence of propranolol in the perfusion medium, unlike atenolol, phenoxybenzamine, guanethidine, verapamil or quinidine, modified the inotropic as well as tachyphylactic responses to insulin. The positive inotropic and tachyphylactic responses to insulin were not altered in hearts from reserpine-treated animals. Perfusion of heart with glucose-free solution abolished the tachyphylaxis due to insulin. Likewise, no tachyphylactic response to insulin was evident when iodoacetate, but not sodium fluoride, was added in medium containing glucose. These results suggest that ATP formed during glycolysis may play an important role in insulin-induced tachyphylaxis with respect to cardiac contractile activity. PMID- 8454374 TI - Effect of calcium channel blockers on serum levels of thyroid hormones. AB - One month oral therapy with calcium channel blockers caused significant (P < 0.001) decrease in serum levels of triiodothyronine and thyroxine and significant increase in serum levels of thyroid stimulating hormone in rabbits. Most probable mechanism of action was block in the synthesis and/or release of thyroid hormones. PMID- 8454375 TI - Cardiocytolytic antimyolemmal antibodies in dilated cardiomyopathy following presentation: observations in 7 patients. AB - The prevalence of lytic activity of circulating antimyolemmal antibodies in dilated cardiomyopathy of recent onset is unclear. To obtain preliminary data we studied 7 consecutive patients with dilated cardiomyopathy (age 44 +/- 14 years) and symptoms for fewer than 6 months. The presence of antimyolemmal antibodies was determined in vitro using intact rat and human cardiocytes and indirect immunofluorescence. Serum cytolytic index for antimyolemmal antibodies was measured by microcytotoxicity assay and the data were compared with that from 70 controls (normal range 0.92 +/- 0.07, effective cytolysis < 0.75). Autoantibody screening was uniformly negative and only 1 patient had positive viral serology. Light microscopy of cardiac biopsies revealed non-specific histology in 2, focal myocarditis in 1 and healing or healed myocarditis in 4. Significant binding of IgG, IgM or polyvalent antibodies to antimyolemmal antibodies bound to rat or human cardiocytes was present in every patient and 5 of them were positive with all 3 markers. Cytolytic index for the group ranged from 0.47 to 0.60 indicating effective lysis in all patients (P < 0.01 versus controls). Cardiocytolytic antimyolemmal antibodies are commonly present in dilated cardiomyopathy following presentation. Their detection might reflect ongoing disease activity and help identify patients likely to benefit from immunomodulative therapy. PMID- 8454376 TI - Immediate cardiovascular responses to orthostasis in the early and late months after cardiac transplantation. AB - Immediate post-standing (< 30 s) heart rate and blood pressure regulation was studied in patients in the early (2 +/- 2 months, n = 10) and late months (49 +/- 18 months, n = 30) after orthotopic heart or heart and lung transplantation with continuous non-invasive blood pressure (Finapress) and ECG recordings, and was compared to 15 healthy subjects. Heart rate acceleration on standing was standing was absent in the early post-transplantation period. Modest, delayed heart rate acceleration (maximum 12 +/- 8 beats/min) was seen late post-transplantation. Subgroup analysis showed that 15 patients late post-transplantation had limited (maximum 6 +/- 3 beats/min) heart rate acceleration, 11 patients showed maximum heart rate acceleration between 11 and 19 beats/min and 4 patients showed heart rate acceleration comparable in magnitude with that of normal subjects (maximum 28 +/- 5 beats/min). The blood pressure transients were comparable in the 3 groups, with a tendency for greater drop and smaller overshoot in systolic blood pressure in transplant subjects. The findings of normal blood pressure transients in the setting of extensive afferent cardiac denervation questions the role of intracardiac (intraventricular) receptors in reflex blood pressure regulation. The development of heart rate responsiveness is compatible with sympathetic reinnervation in many patients in the late post-transplantation period; however, an intrinsic cardiac mechanism may also be possible. PMID- 8454377 TI - Effects of tissue plasminogen activator therapy on the frequency of acute right ventricular myocardial infarction associated with acute left ventricular infarction. AB - To assess the effects of reperfusion therapy on acute right ventricular myocardial infarction, we studied at necropsy the hearts from 51 patients who died after receiving intravenous recombinant tissue plasminogen activator for acute left ventricular myocardial infarction as part of the Thrombolysis in Myocardial Infarction (TIMI) study. Right ventricular infarction occurred in none of 29 patients with infarction of the anterior wall of the left ventricle and in 8 of 22 patients (36%) with infarction of the posterior (inferior) wall of the left ventricle. Of the 22 patients with posterior wall infarction, the 8 patients with right ventricular infarction were compared to the 14 patients without right ventricular infarction. The patients with right ventricular infarction had a longer mean interval from tissue plasminogen activator infusion to peak creatine phosphokinase level (19 vs. 11 h, P < 0.03), a lower frequency of hemorrhagic necrosis (2 of 8 vs. 10 of 14, P < 0.04) and higher frequency of luminal thrombus in the infarct-related coronary artery (6 of 8 vs. 3 of 14, P = 0.054). Each of these findings is associated with the absence of coronary reperfusion. Thus, successful reperfusion following acute left ventricular myocardial infarction appears to be associated with a decreased frequency of concomitant right ventricular myocardial infarction. PMID- 8454378 TI - Implications of coronary angiography in patients with suspected or known coronary artery disease. AB - The study analyzes the incidence of coronary lesions and their implications on the treatment offered in 500 consecutive non-selected patients (406 males (81%), age 60 +/- 10 (+/- 1 standard deviation), range 21-88 years) undergoing coronary angiography for suspicion or confirmation of coronary artery disease (excluding patients with congenital and pure valve disease, or cardiomyopathy). A history of myocardial infarction was present in 205 patients (41%). There were no prior cardiac procedures in 334 patients (67%). There was prior coronary angioplasty in 82 patients (16%), coronary artery bypass grafting in 44 (9%) and both in 4 (1%). A total of 36 patients (7%) had had prior coronary angiography only. Mean left ventricular ejection fraction was 61 +/- 12 (18-83%) and mean left ventricular end diastolic pressure was 12 +/- 6 (2-37) mmHg. Angiographically normal coronary arteries were present in 61 patients (12%) and non-significant coronary lesions in 70 patients (14%). One vessel disease was present in 169 patients (34%), two vessel disease in 97 (19%), three vessel disease in 88 (18%) and left main coronary artery disease in 15 (3%). In single vessel disease, involvement of the left anterior descending coronary artery was seen in 82 patients (49%), left circumflex coronary artery in 38 (22%) and right coronary artery in 49 (29%). In two vessel disease, involvement of the left anterior descending coronary artery and left circumflex coronary artery was present in 30 patients (31%), left anterior descending coronary artery and right coronary artery in 36 (37%) and left circumflex coronary artery and right coronary artery in 31 (32%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454379 TI - Placebo-controlled trial of flosequinan in moderate heart failure. The possible importance of aetiology and method of analysis in the interpretation of the results of heart failure trials. AB - One hundred-thirty five patients with moderate heart failure, recruited from 18 centres, were included in a double blind, placebo controlled study to evaluate the effects of flosequinan on symptom limited tread-mill exercise tolerance. Fifteen patients in the placebo group were withdrawn from the study compared with 14 from the group given flosequinan. New York Heart Association classification was improved at week 16 in the flosequinan group relative to those randomised to placebo (P < 0.01). Depending how the other results are analysed flosequinan either appeared to have no effect on symptom limited exercise tolerance in those who completed the study; a suggestion of superiority if an analysis at endpoint is used (P = 0.09), or, if a covariate analysis at endpoint is used, then a significant improvement can be demonstrated (P = 0.04). Subset analysis suggests that the aetiology of the heart failure and the dose of diuretics used might have a major effect on the response to treatment. The best way of analysing clinical trials in heart failure is not clear as the results can be profoundly influenced by the way data from withdrawn patients are handled. The aetiology and diuretic requirement of patients may influence their response to treatment. PMID- 8454380 TI - Changes in frequency domain measures of heart rate variability in relation to the onset of ventricular tachycardia in acute myocardial infarction. AB - The imbalance of the autonomic nervous function has been shown to contribute to the genesis of ventricular arrhythmias. Power spectral analysis of components of heart rate variability has the potential to quantify the cardiac autonomic tone during ambulatory electrocardiographic recording. We analysed the power spectral components of total power, very low frequency power (0.0033-0.04 Hz), low frequency (0.04-0.15 Hz) and high frequency (0.15-0.40 Hz) power in 12 consecutive patients accompanied with 27 episodes of ventricular tachycardia in acute myocardial infarction. The spectral areas were measured in 5-min periods preceding the onset of ventricular tachycardias. The total power of heart rate variability increased progressively before the onset of ventricular tachycardia episodes (P < 0.05). The increase of total power was mainly due to higher, very low frequency power at the onset rather than before the onset of ventricular tachycardia (P < 0.05). The trend towards adrenergic predominance at the onset of ventricular tachycardia was observed by an increase of average heart rate (P < 0.05) without concomitant increase in high frequency power. Thus, the occurrence of ventricular tachycardia is associated with changes in the power spectrum of heart rate variability suggesting alterations in autonomic tone at the onset of ventricular tachycardia in acute myocardial infarction. PMID- 8454381 TI - Concurrent percutaneous balloon valvotomy for combined rheumatic tricuspid and aortic stenosis. AB - Concurrent percutaneous balloon valvotomy of aortic and tricuspid valve was successfully performed in a 20-year-old male with severe rheumatic aortic and tricuspid stenosis. Balloon valvotomy was done using a 18-mm single balloon for aortic and 20 + 20-mm double balloon for the tricuspid valve. Immediately after valvotomy the peak transaortic systolic gradient decreased from 120 to 32 mmHg and the aortic valve area increased from 0.27 to 1.1 cm2, the mean and end diastolic trans-tricuspid gradient decreased from 14 and 18 to 1.5 and 2 mmHg, respectively, the tricuspid valve area increased from 0.8 to 3.6 cm2 and the cardiac-index increased from 2 to 2.9 l/mt/m2. At 1 year of follow-up the clinical (NYHA class 1) and hemodynamic improvement was maintained. PMID- 8454382 TI - Spontaneous reversion of long-lasting chronic atrial fibrillation to sinus rhythm. AB - We report a case of a 72-year-old lady with rheumatic heart disease and chronic, long-lasting atrial fibrillation, who reverted spontaneously to sinus rhythm. Doppler study showed evidence of mechanical contraction of the right but not of the left atrium. This may be a sign of marked histologic changes in the atria and may require the insertion of a permanent pacemaker, because of subsequent development of sinus bradycardia. PMID- 8454383 TI - Rheumatic mitral stenosis associated with hypertrophic cardiomyopathy and anomalous muscle bundle in the right ventricle. AB - Clinical, echocardiographic, haemodynamic and angiographic features of a patient with rheumatic mitral stenosis, hypertrophic cardiomyopathy and anomalous muscle bundle in the right ventricle are presented. At the bedside, the presence of left ventricle type apex beat, left ventricle S4 gallop, ejection systolic murmur at the left mid sternal border and electrocardiographic evidence of left ventricular hypertrophy in a patient with classical findings of mitral stenosis in the absence of significant mitral regurgitation and aortic valve disease should suggest this extremely rare association of mitral stenosis with hypertrophic cardiomyopathy. PMID- 8454384 TI - Blunt chest trauma causing right atrial tear, hemopericardium and cardiac tamponade successfully treated with cardiorrhaphy. AB - A 26-year-old female was involved in a car accident with impaction of the steering wheel to the anterior chest. She became unconscious immediately. Blood pressure was unmeasurable, central venous pressure was measured at 25 cm H2O. Cross-sectional echocardiography revealed pericardial effusion and a band-like blood clot in the posterior inferior aspect of the heart. At operation, a right atrial tear measuring 1 cm in length was noted and was repaired with cardiorrhaphy. She recovered uneventfully. PMID- 8454385 TI - Congenital quadricuspid aortic valve. AB - Two patients with a quadricuspid aortic valve are described, one of them with concomitant juxtaposed coronary orifices facing the right hand facing sinus. The etiology and incidence of this congenital anomaly will be discussed. PMID- 8454386 TI - Right ventricular cardiomyopathy similar to Uhl's anomaly with atrial flutter and complete AV block. AB - We report an adult patient with right ventricular cardiomyopathy similar to Uhl's anomaly. In this patient an interesting manifestation is a transient atrial flutter with complete A-V block. Right ventricular cardiomyopathy (arrhythmogenic right ventricular dysplasia) is considered a cause of life-threatening arrhythmia. The right ventricular musculature is partially or totally absent and is replaced by fatty and fibrous tissue. Patients may present with ventricular arrhythmias, right heart failure or asymptomatic cardiomegaly. Only a few cases with atrioventricular conduction disturbance have been reported in the literature by now. We report such a case. PMID- 8454387 TI - Stokes Adams attack as the first manifestation of acute rheumatic fever. PMID- 8454388 TI - Effects of prenatal litter size in inbred mice on morphometric characters with different developmental patterns. AB - Prenatal litter size effects were assessed in two inbred, cross-fostered strains of house mice (A/J and C57BL/10J) in order to see whether they differed among morphometric characters with different developmental histories. Three characters were used: body size, which exhibits both prenatal and postnatal development; the width of the second mandibular molar (M2), which exhibits mostly prenatal development; and the width of the third mandibular molar (M3), which exhibits all postnatal development. Prenatal litter size regressions differed significantly between fostered and non-fostered groups for each of the three characters in at least one of the two inbred strains, and as hypothesized, tended to be more negative in sign for the M2 versus the M3. Prenatal litter size differences accounted for 19% of the total variation in body size, but just 5% in both molar widths. Prenatal litter size also significantly affected the covariation among the characters, and in a direction consistent with their developmental histories. It was concluded that prenatal litter size can significantly affect a number of morphometric characters and that the magnitude and nature of these effects may be related to the developmental patterns of the characters. PMID- 8454389 TI - Effect of thiouracil-induced hypothyroidism on time course of adrenal response in 15 day old rats. AB - Previous investigations have supported the suggestion that perinatal induction of hypothyroidism, using the goitrogen thiouracil, completely prevents elevation of circulating corticosterone levels 15 min after ether stress in 15 day old rats. The present study used radioimmunoassay (RIA) to evaluate the effect of chemical hypothyroidism on response of circulating corticosterone to ether stress, or to exogenous corticotropin releasing factor (CRF), at 15, 30, or 45 min after stimulation. Fifteen day old hypothyroid rat pups responded to ether stress with a linear increase in circulating corticosterone over the time course of the study, and with the levels at 30 and 45 min significantly greater than unstimulated. However, the slope of the increase was markedly subnormal, as was corticosterone level at each time point after stress. On the other hand, CRF injection resulted in elevations of corticosterone along the time course that were similar for normal and thiouracil exposed rats. The results of this study do not support the previous conclusion that chemical hypothyroidism entirely abolishes adrenal axis response in 15 day old rats. Instead, thiouracil depresses the response at a number of post-stimulation time points, rather than causing a time-dependent delay in a normal corticosterone elevation. This is likely the result of thiouracil-induced functional deficits in all components of the neuroendocrine axis regulating corticosterone secretion, with particularly severe effects at the hypothalamus. PMID- 8454390 TI - Parental age effects on body size and growth rate in guppy-fish. AB - We analysed the effect of parental ageing on variations in body size and growth rate of guppy-fish progeny. The resulting data showed that the mean body length of the progeny increases with advancing parental age and this increase might be due to a faster growth rate of progeny from older parents. Given the high correlation linking parental age and maternal size, the involvement of size cannot be ruled out, even though parental age had a greater effect than maternal size on the body length of progeny in one of the two populations considered. Variation in progeny growth rate in relation to variation in parental age might be due to an adaptive mechanism which allows the offspring of older parents to reach reproductive age faster. PMID- 8454391 TI - Body and muscle growth of domestic turkeys (Meleagris gallopavo) and expression of myosin heavy chain isoforms in breast muscle. AB - Growth characteristics of breast (pectoralis) muscle of male Large White hybrid turkeys were described using the von Bertalanffy model and Huxley's allometric growth analysis, and the cellular maturation process of breast muscle was studied by examining the relationship between the timing of appearance of myosin heavy chain isoforms and circulating levels of thyroid hormones. The inflection points at which the maximum growth rate occurred were estimated to be 112 days for the body weight and 159 days for the breast-muscle weight. The allometric growth coefficient for pectoralis muscle, relative to the whole-body growth, was 1.23 and significantly greater than those of the gastrocnemius, sartorius, latissimus dorsi and extensor digiti muscles during the first 12 weeks posthatch. Myosin was prepared from pectoralis muscle of turkeys at ages ranging from 15 days of incubation (embryos) to 308 days (adult), and embryonic, neonatal and adult isoforms of myosin heavy chain were detected by monoclonal antibodies in the enzyme-linked immunosorbent assay. In turkey embryos, the embryonic myosin heavy chain isoform appeared by 22 days of incubation. The transition from embryonic isoform expression to neonatal isoform expression was noted shortly after hatch, and the transition from neonatal to adult was initiated at 7 days posthatch and was nearly completed by 28 days posthatch. The circulating thyroxine concentration rose and fell markedly around the time of hatch and fluctuated within the range of 11 to 19 ng/ml. The triiodothyronine concentration fluctuated within the range of 5 to 7 ng/ml after hatch and started to fall at 14 days posthatch to reach the adult level of 3 to 5 ng/ml. PMID- 8454393 TI - The Rani of Chitor: the face. AB - In this paper the author introduces a psychoanalytic concept: the face. This concept has two aspects: it is the particular form in which the subject's identity is revealed to him, and it also demonstrates how the analyst works in the sense of allowing the patient to discover who he is. For this purpose the author makes use of a Hindu legend, which he does not interpret conventionally but narrates, inviting the reader to learn with it. The foundations of this approach lie in the results of his research on the psychoanalytic method and in his consequent position with respect to psychoanalysis: field theory. Fixed interpretive keys are not used; the material, the legend, throws light on an aspect of psychoanalysis itself, while psychoanalysis illuminates the material. The theoretical and methodological reorganisation suggested here helps us to understand the nature of psychoanalytic interpretation and how analysis works in the investigation of the face of human desire. PMID- 8454392 TI - Effect of dietary fat and aging on adipose tissue cellularity in mice differing in genetic predisposition to obesity. AB - A line of mice had been developed which became obese when fed a commercial mouse breeder chow. This obese line was compared to a non-obese line at various ages to determine whether the type or amount of dietary fat would affect adipocyte size and number. Experimental diets containing beef tallow (38% of calories as beef fat and 2% as corn oil), corn oil (40% corn oil) or low fat (2% corn oil) were provided ad libitum at the time of weaning. Dorsoscapular subcutaneous fat pads were removed at 5, 6, 7, and 8 weeks and at 3, 6, 9, 12, 15, 18, and 21 months of age. Adipocyte size and number were determined histologically. Obese mice had enhanced adipocyte hyperplasia compared to the non-obese line. Only when eating the low fat diet did the obese mice have life-long elevated hypertrophy compared with their non-obese counterparts since non-obese mice responded to high fat feeding with a dramatic increase in adipocyte volume, regardless of type of fat. Body weight was greater in the obese line at all ages studied; however, some overlap in body weight was encountered between non-obese mice fed the high fat diets and genetically obese mice. Non-obese mice fed the low fat diet were smaller than mice in all other treatment groups throughout the study. Weight of the dorsoscapular subcutaneous adipose tissue was consistently greater in the obese line; however, high fat feeding greatly increased fat pad weight in non obese mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454394 TI - Freud's speech apparatus and spontaneous speech. AB - Freud's first book published in 1891 was a monograph entitled On Aphasia. In it he challenges the main authorities of the time by asserting that their manner of understanding aphasias is no longer tenable. Freud proves their theories wrong and presents his own conception of a speech apparatus. The apparatus is the foundation of his clinical and theoretical explanations about the speech function and its pathological manifestations. He built the model of an apparatus capable of explaining spontaneous speech, a function that the competing models of his contemporaries could not fully integrate. Freud's speech apparatus is the first of several models he created to facilitate the understanding of psychic functions. This paper is part of a series dedicated to an in-depth study of the earliest model which would provide the foundations for the understanding of its reappearance in Freud's later theories, and in particular in his analytic technique. PMID- 8454395 TI - Acting out and transference themes induced by successive pregnancies of the analyst. AB - The analyst's pregnancy can be considered a major organiser of the unfolding transference. In a detailed account of the analysis of a female patient who was confronted twice with the pregnancy of the analyst, the similarities and differences of the transference on both occasions are highlighted, with special emphasis on the occurrence of acting out. An analyst's pregnancy intensifies the transference and requires from the patient the capacity to experience the intensity of the evoked feelings. Accordingly, acting out is shown to be more vehement in the course of both pregnancies. The further the analytical process has evolved, the better these feelings are tolerated and the more susceptible they are to subsequent analysis. PMID- 8454396 TI - The analyst's pregnancy and its consequences on her work. AB - In this paper I discuss with clinical examples how the analyst's pregnancy may affect the analysis in unique, subtle and at times unexpected ways to which the analyst must be alert. Like any major psychosocial crisis in the life cycle, pregnancy challenges the analyst's ability to hold on to the psychoanalytic attitude. It also confronts her with specific issues (primitive anxieties about the inside of the body, fears of loss of identity, of damage to the foetus etc.) which have to be acknowledged and which require consistent and at times painful working through. Overall, my experience was that by and large positive emotional growth took place, both in the patients and myself, during the pregnancy. I would suggest that the possible changes were not only due to the pregnancy per se but to the careful analysis of its effects which allowed for the psychoanalytic situation to be maintained. PMID- 8454397 TI - The mind of the analyst: from listening to interpretation. AB - The analyst demands two somewhat contradictory attitudes of himself: on the one hand, he listens and interprets on the basis of his theoretical knowledge, experiences and scheme of reference and, on the other, he must open himself to the new, the unforeseen and the surprising. His work, from listening to interpretation, is situated within a context that includes the history of the treatment as well as the history of the analysand, which is in the process of reconstruction. This context determines the moment of the interpretation (which may vary), i.e. the point ot urgency of a given session. This point denotes the moment when something emerges from the unconscious of the analysand and the analyst believes that it must be interpreted. It is something that occurs within the intersubjective field, which embraces both participants and has its own, partly unconscious, dynamics. This configuration or unconscious fantasy of the field constitutes the common source from which both the discourse of one partner and the other's interpretation spring. The moments of blockage in the dynamics of the field, the obstacles in the analytic process, invite every analyst to take a 'second look' at the field, focusing on the unconscious intersubjective relationship which determines it. Focused either on the analysand or on the field, the interpretation can perform its two dialectically complementary functions: it may irrupt into the disguises of the patient's unconscious, or it may allow him to synthesise and reconstruct his history and identity. PMID- 8454398 TI - The analyst's pregnancy: the patient, the analyst, and the space of the unknown. AB - In this paper I have discussed some thoughts about the effect of the analyst's pregnancy on her patients, using material from my own experience. In the first part of the paper I have examined some of the issues evoked in the countertransference especially in the first trimester of pregnancy, when, because of my concern about the health of the foetus I was reluctant to inform patients of my state. In the latter part of the paper I have focused on some of my patients' responses as expressed in the transference: in particular on the question of how patients dealt with learning of and thinking about my pregnancy, which involved a threat to the sense of unity, fusion and non-separateness from me that in some cases were of paramount importance. To do this I have discussed at some length clinical material relating to two patients, the first a woman whose own pregnancy followed mine, in an imitative fashion that both denied any difference between us and also allowed her to develop her capacity to be a mother; the second a man who initially understood my pregnancy as rejecting of him, persecuting and guilt-provoking, and saw it as an event either unthinkable and/or to be dealt with omnipotently. PMID- 8454399 TI - Between chaos and petrification: a summary of the Fifth IPA Conference of Training Analysts. AB - The Fifth IPA Conference of Training Analysts was devoted to the problems in the integration of different theoretical and clinical perspectives in the formation of psychoanalysts, the dialectical tensions between rigidity and stultification on the one hand, and a chaotic 'anything goes' on the other. Seven presentations, from the three major geographical regions and representing a range of theoretical perspectives, though drawing upon common and shared clinical and training experiences, were widely divergent in both their descriptions and their prescriptions. The presentations by Janice de Saussure of Geneva, by Charles Kligerman of Chicago, by Marcio de Freitas Giovanetti of Sao Paulo, Raquel Zak de Goldstein of Buenos Aires, Andre Green of Paris, Jose Infante of Chile and Andre Lussier of Montreal, are arrayed along a spectrum from the most conservative to the most sweepingly radical critique of our organisations and our practices; what is shared by these seven quite disparate presentations from so many ideologically and geographically diverse quarters is a widespread dissatisfaction with so many aspects of, and so many consequences of, the operation or our extant tripartite training structure bequeathed to us by Eitingon and his colleagues almost 75 years ago and hardly changed at all ever since. PMID- 8454400 TI - Freud's Irma Dream. PMID- 8454401 TI - To be or not to be a patient. PMID- 8454402 TI - Theory in vivo. AB - Due to a formerly held assumption that psychoanalytic theories operate exclusively in the positivistic manner associated with the natural sciences, current thinking on how they operate specifically or in their own terms is addressing a long-neglected task. In this paper it is suggested that inherent and acquired modes of theorizing interplay when an analyst is working; and that a dialogue involving these two modes which began in Freud's inner life has evolved into our communal conceptual discourse. A series of situationally connected interchanges with a female analysand, over a two-week period, is presented. An attempt is made to demonstrate some theorizing, not 'in vitro'--'in the test tube' of abstraction, but where most use and discovery of theory happens, 'in vivo'--within the living experience of therapeutic analysis. PMID- 8454403 TI - Narrative representation, narrative enactment, and the psychoanalytic construction of history. AB - This paper develops the idea that the fundamental tension between representation and enactment described by psychoanalytic historical theories also determines and limits our theorizing attempts themselves. Freud moves toward this recognition in his late work as he brings a challenge to the lifting-of-repression model of historical recovery. One basis of this challenge is that Freud now implicates the analyst, as well as the analysand, in the tension between the capacity of historical narratives to represent the past, and their tendency to enact it. From the perspective of Freud's explicitly dialogic model in 'Constructions in analysis', the task of establishing historical reference in psychoanalysis cannot be separated from the narrative actions of the analyst. These narrative actions would necessarily include manifestations of denial and disavowal that I designate as 'narrative enactments'. My discussion expands upon this linguistic dimension of questions Freud raises about the limits of the psychoanalytic construction of history. Narrative enactments work against an interpretive restoration of historical reference based upon the lifting of repression, but at the same time, seen as an aspect of narrative functioning, they are founding acts upon which our historical constructions rest. PMID- 8454404 TI - On the clinical usefulness of the concept of death instinct. AB - Freud's concept of the death instinct is often considered as a purely biological speculation, and very few psychoanalysts consider it useful in clinical work. Yet Freud was led to it by purely clinical problems. Klein used Freud's concept of the duality of instinct in her clinical work, but mainly she addressed herself to the conflict between love and hate of the object, considering hate as an expression of the deflected death instinct. I contend that the death instinct from the beginning is directed at both the perceived object and the perceiving self, resulting in such phenomena as pathological projective identification, described by Bion. The defences against the death instinct create vicious circles leading to severe pathology. I try to show in some clinical examples how analysing those vicious circles, and confronting the death instinct in the stable setting of analytic work, can lead to a mobilisation of the life forces in the patient. PMID- 8454405 TI - Truth and reality in psychoanalytic discourse. AB - In this paper, I examine the influences of two philosophical theories of truth- coherence and correspondence--on the current debate on the search for 'common ground' and on specific aspects of clinical practice. Results from a previous empirical study of analysts' approaches to transference interpretation are described in order to illustrate the way in which a network of clinical concepts is held together by explicit and implicit beliefs concerning the nature of subjectivity, truth and reality. Excerpts from interviews of psychoanalysts of varying orientations practising in different geographical locations indicate the complex interrelationships between concepts of analytic neutrality, extra transference, the real relationship, countertransference, the death instinct and the therapeutic alliance. These findings suggest that the coherence versus correspondence theories of truth may constrain rather than enhance the investigation of the differences and commonality between varying analytic theories, schools and clinical practices. PMID- 8454406 TI - The inner experiences of the analyst: their contribution to the analytic process. AB - As an illustration of the inner experiences of the analyst as they operate in the analytic situation, this paper presents a single analytic hour in some detail. By means of this clinical material, the author seeks to demonstrate how the thoughts, fantasies, memories, bodily movements and autonomic responses that he experienced in this hour affected his interventions, the kinds of transference countertransference interactions that developed in the session, and the unfolding of the analytic process. PMID- 8454407 TI - A speculation on perversion and hallucination. AB - This study develops a new explanation for the loss of reality in perversion. It is a speculative effort, and draws heavily on Freud's metapsychology. I have reviewed Freud's concept of the experience of satisfaction, and have described tests of reality implicit in the experience. Freud did not put these forward as reality-tests, but this they logically become from his own arguments. These reality-tests can be shown to be at work in the perverse solution to overwhelming anxiety. In particular, the pervert exploits them to create body or motor hallucinations or delusions which serve to deny castration anxiety and other concomitant traumatic situations. PMID- 8454409 TI - Cytokine-induced pathology. Part A: interleukins and hematopoietic growth factors. PMID- 8454408 TI - On ambiguity, confusion and the ego ideal. AB - This paper discusses the problem of ambiguity as a form of narcissistic resistance that alters the meaning of words and hinders communication and access to the unconscious. The ego uses ambiguity to avoid and project confusion. Pathological ambiguity is differentiated from other forms of ambiguity which do not hinder communication. Though they share a common element--oscillation between two opposites--the mechanism involved in this form of ambiguity differs from the mechanism involved in thought processes, ambivalence and metaphor. Two examples are used to investigate the problem of ideals and ego splitting. Ambiguity corresponds to a disorder whereby two contradictory ideals co-exist within the ego ideal. One ideal fixes the discovery of the unconscious as a goal. The other ideal over-values acting out. The result is that the ego tends to obtain self esteem through goals that lead to error and it is this quest for error that sustains the feeling of omnipotence. PMID- 8454410 TI - Pathology induced by hematopoietic growth factors. Introduction. PMID- 8454411 TI - Comparative toxicity of Escherichia coli and yeast rHuIL-3 in cynomolgus and rhesus monkeys. PMID- 8454412 TI - Preclinical safety assessment of recombinant human GM-CSF in rhesus monkeys. PMID- 8454413 TI - Clinical and histopathological effects of M-CSF in laboratory animals. PMID- 8454414 TI - Review of a novel hematopoietic cytokine, interleukin-11. AB - The novel stromal cell factor, IL-11, has been reported to have diverse effects on the lymphopoietic and myeloid/erythroid cells in vitro. These include expansion of T cell-dependent Ig-secreting B cells, proliferation and differentiation of megakaryocytic progenitors and of a variety of myeloid and erythroid precursor cells, and multiplication of pluripotential hematopoietic progenitors. In addition, IL-11 inhibits adipogenesis in vitro. In vivo administration of IL-11 elevated the number of circulating neutrophils and platelets and increased the number of megakaryocytes in the spleens of normal mice. PMID- 8454415 TI - Pathology induced by interleukins. Introduction. PMID- 8454416 TI - Pathogenesis of toxicity with human-derived interleukin-2 in experimental animals. AB - It should be pointed out that although repeated systemic administration of exogenous rIL-2 in nonphysiological doses to mice, rats, and monkeys produced various toxicity-related exaggerated pharmacodynamic effects in many experimental parameters, pathological findings were substantially similar among all species. Furthermore, because toxicities observed in our studies were identical to those reported in humans dosed with rIL-2, preclinical toxicity using animal models was fully predictive of the pathogenesis of rIL-2 in human. With continuous infusion, which maintained high blood concentrations of the product during the course of the study, rIL-2 constantly stimulated proliferation of lymphoblastoid cells in peripheral blood, subsequently causing vascular leakage, which consists of edema and extravasation of activated lymphoblastoid cells into perivascular areas. The migrating lymphoblastoid cells, identified as cytotoxic T lymphocytes and NK-LAK cells, caused perivascular and hepatocytic necrosis by means of enzymatic secretions from the cells in association with infiltration into parenchymal tissues. In addition to the stimulation of lymphoblastoid cells in peripheral blood, prolonged daily bolus administration of rIL-2 induced extravasation and infiltration of activated macrophages and B cells in tissues of all organs. Eosinophilia, fibrosis in the subcutis, or pseudolobular formations in the liver could be mediated by systemic release of many other cytokines from activated T cells, i.e., CTLs or LAK cells, B cells, and macrophages. PMID- 8454417 TI - Comparative toxicity and pathology associated with administration of recombinant IL-2 to animals. PMID- 8454418 TI - Pathology induced by interleukin-6. AB - Interleukin-6 (IL-6) is a multifunctional cytokine that plays an important role in the immune response, hemopoiesis, and host defense. Recombinant human IL-6 (rhIL-6) was administered at high doses to mice, rats, and nonhuman primates. In all species, IL-6 had an immunostimulatory and hemopoietic (especially on megakaryocytes) effect. An acute-phase response was most pronounced in nonhuman primates, which was, however, not associated with any significant histopathological liver change. Finally, no evidence of glomerular pathology was found. Neutralizing antibodies were detected within 10 days of rhIL-6 administration in all species. PMID- 8454419 TI - Comparative toxicity and pathology associated with administration of recombinant HuIL-1 alpha to animals. PMID- 8454420 TI - Interleukin-6 in myeloma/plasmacytoma. PMID- 8454421 TI - Interleukin-9. PMID- 8454422 TI - [Pathologic anatomy and immunohistology of non-Hodgkin's lymphoma]. PMID- 8454423 TI - [Cytogenetics of malignant lymphoma]. PMID- 8454424 TI - [New developments in diagnosis of malignant lymphoma]. PMID- 8454425 TI - [Clinically relevant prognostic factors in malignant lymphoma]. PMID- 8454427 TI - [Therapeutic strategies of highly malignant non-Hodgkin's lymphoma]. PMID- 8454426 TI - [Therapeutic strategies of mildly malignant non-Hodgkin's lymphoma]. PMID- 8454428 TI - [Therapeutic strategies of Hodgkin's disease]. PMID- 8454429 TI - [Diagnosis and therapy of gastrointestinal lymphoma]. PMID- 8454430 TI - [Long-term toxicity of curative lymphoma therapy]. PMID- 8454431 TI - [Differential coronary interventional therapy in a 39-year-old male patient with generalized arteriosclerotic vascular disease and nephrotic syndrome]. PMID- 8454432 TI - [Abdominal pain in mesenteric space-occupying lesion]. PMID- 8454433 TI - [Calcium antagonists. Part 1: Pharmacology]. PMID- 8454434 TI - [Calcium antagonists. Part 2: Clinical applications]. PMID- 8454435 TI - [Is compression therapy of acute deep vein thrombosis of the leg always indicated for promoting venous flow (a basic measure)?]. PMID- 8454436 TI - [Protein electrophoresis]. PMID- 8454437 TI - [Cellular and molecular biology of malignant lymphoma]. PMID- 8454438 TI - Effect of age and duration of disease on the clinical manifestations of brucellosis. A study of 73 consecutive patients in Israel. AB - We describe our experience with 73 patients diagnosed with brucellosis during the years 1979-91 at two Jerusalem hospitals: Hadassah Mount Scopus (37 patients from 1979-1984) and Shaare Zedek (36 patients from 1979-1991). The patients included 32 children less than 14 years old and 41 adults; 70 of the patients were non Jews. In all cases the pathogen was Brucella melitensis. The high proportion of children and the equal sex distribution was quite different from the age and sex distribution of brucellosis in Western countries where it is more common in adult males, and similar to that reported from other near-Eastern countries where household dairy products, and not occupational exposure, are the most common source of infection. The short duration of disease (< 2 weeks) prior to diagnosis in 70% of the patients is attributed to the ready availability of appropriate medical care, and a very high index of suspicion for brucellosis in the Jerusalem non-Jewish population. Abdominal symptoms were more common in adults, whereas enlarged lymph nodes and liver, skin rash and pharyngitis were more frequently observed in children. Some of these differences may be attributed to the very short duration of disease in most children at the time of presentation. Combination therapy with tetracycline-streptomycin or tetracycline-rifampin yielded superior results as compared with single-drug treatment in terms of early defervescence and relapse rates. The present experience underlines the importance of endemic brucellosis which still represents a significant public health problem in children and adults in Mediterranean countries. PMID- 8454439 TI - Real-time monitoring of visual evoked potentials. AB - Steady-state visual evoked potentials (SSVEP) were recorded in response to flashes from eyepatch-mounted light-emitting diodes during neurological surgery and in the intensive care unit. SSVEP were detected and measured with a microprocessor-based waveform correlator. The system enabled a continuous display, in real time, of SSVEP amplitude and latency. SSVEP amplitude and latency changes were monitored throughout a variety of surgical procedures. Some of these procedures directly affect the central visual pathway, some affect the central nervous system as a whole, while others do not affect central nervous system function. In addition, intensive care unit patients with a variety of intracranial pressures were monitored. The results of this study indicate that SSVEP recorded with this method showed changes in SSVEP within seconds of surgical and/or medical decompression of intracranial pressure and were sensitive to specific changes in the visual pathway. Surgical procedures that directly affected the visual system, or elevation of intracranial pressure, resulted in changes in SSVEP. In contrast, procedures that did not affect the functional integrity of the visual system did not affect the recordings. PMID- 8454440 TI - Inhibitory effect of the calcium antagonist, verapamil, on measles and vaccinia replication in cell culture. AB - Kidney cell lines MA104 and BGM were infected with vaccinia and measles viruses respectively in the presence of 45Ca. Increased 45Ca level was detected in the virally infected cells as compared with control cells. An enhancement of 28 +/- 6% and 37 +/- 13% was shown in vaccinia and measles respectively following 5 h of infection. The effect of the calcium antagonist verapamil was studied in both vaccinia- and measles-infected cells. In one-step growth experiments, the mean inhibitory effect of 90 microM verapamil on viral yield after 13 h was 97 +/- 1% in the case of vaccinia. In the measles virus after 47 h a mean of 76 +/- 5% inhibition was detected. The suitability of verapamil as a potential antiviral agent is suggested and requires further investigation. PMID- 8454441 TI - Delayed hyperbaric treatment of cerebral air embolism. AB - Urgent exposure to hyperbaric oxygen (HBO) is currently accepted as an effective therapy for cerebral air embolism. The diagnosis of air embolism in the critically ill post-surgical patient is frequently difficult and therefore the initiation of specific therapy is often delayed. Only limited information is currently available on the effects of delayed HBO treatment in these patients. We recently used HBO to treat five patients with cerebral air embolism resulting from invasive medical procedures; hyperbaric treatment was begun 15-60 h after the embolic event. The causes of air embolism were: cardiopulmonary bypass accidents, pulmonary barotrauma induced by mechanical ventilation, and central vein catheterization. All patients received initial treatment according to U.S. Navy Compression Table 6A in a multiplace chamber, followed by subsequent treatments with 100% O2 at 2.5 to 2.8 ATA for 90 min as indicated. Significant, partial or complete recovery was observed in three patients, one patient did not respond, and one died. The salutary effects of HBO in our subgroup of patients suggest that this treatment should be used in cerebral air embolism even when referral to a hyperbaric facility is delayed. PMID- 8454442 TI - Improved results in osteogenic sarcoma 1973-79 vs. 1980-86: analysis of results from a single center. AB - Analysis of treatment results in osteogenic sarcoma patients with classical limb primary tumors and without metastasis at diagnosis or major protocol violations showed improved prognosis with a minimum follow-up of over 5.5 years when divided by years of treatment for all event-free survivors. Twelve patients treated in 1980-86 had a 5-year disease-free survival of 67% and 9 treated in 1973-79 had a 5-year disease-free survival of 33% (P = 0.0368). The improvement appeared to reflect the increase in the intensity of the chemotherapy utilized. Definitive surgery, amputation or limb salvage did not affect the outcome. With these surgical approaches the disease-free survival was 67% and 60% respectively. PMID- 8454443 TI - Prevalence of antibodies to Toxoplasma gondii in the Tel-Mond area. AB - Sera from 1,315 inhabitants of the Tel-Mond area were tested by the indirect immunofluorescent and Sabin Feldman tests for Toxoplasma antibodies. The overall prevalence of antibodies was 29.3%. Antibodies rose with age from 9.9% in the 1-4 year age-group up to 40.9% in the 45 age-group. There was no significant difference in prevalence of antibodies between the sexes. The prevalence of antibodies to Toxoplasma was lower in those born in Israel (21.2%) than in immigrants from Europe, America, Australia (49.4%), and Africa, Asia (40.8%) in the age groups of 20-45+. An extremely high prevalence of antibodies (41.5%) was found in Moshav Porat, a low socioeconomic settlement. PMID- 8454444 TI - Patterns of unjustified pediatric hospital stay. AB - We examined the pattern of hospital stay in a pediatric division of a major teaching medical center in terms of justification of the hospital stay. Hospital stay days of all children admitted during 3 consecutive weeks were assessed prospectively according to predetermined criteria. Of the 2,048 hospital stay days 26% were unjustified, primarily due to unnecessary in-hospital follow-up and diagnostic evaluation that should have been carried out on an ambulatory basis. Logistic regression analysis revealed that neurological disorders and trauma, age younger than 3 years, specific ward, and the attending physician were significant predictors for unjustified hospital stay days. This method is proposed as a means for optimal reduction of redundant hospital stay and concomitant unnecessary economic burden. PMID- 8454445 TI - Maimonides (Moses ben Maimon, Rambam). PMID- 8454446 TI - Inhaler salbutamol for acute hyperkalemia in renal failure. PMID- 8454447 TI - The distribution and density of Langerhans cells in the human prepuce: site of a diminished immune response? PMID- 8454448 TI - Macrophage migration inhibition test in patients with drug-induced pemphigus. PMID- 8454449 TI - "Low normal" hemoglobin concentration in black Arabs. PMID- 8454450 TI - Listeria monocytogenes endocarditis in a patient with a prosthetic aortic valve. PMID- 8454451 TI - Cardiomyopathy in lipodystrophy and the specificity spillover hypothesis. PMID- 8454453 TI - Non-O group 1 Vibrio cholerae septicemia in Israel. PMID- 8454452 TI - Ceftriaxone-induced agranulocytosis. PMID- 8454455 TI - Vitamin enrichment of basic foods: the case-for-action in Israel. PMID- 8454454 TI - Radon in 1,500 Israeli homes and workplaces. PMID- 8454456 TI - Management of congestive heart failure: neuroendocrine approach. AB - The term heart failure is a complex of clinical syndromes caused by "neuroendocrine" compensatory responses that are renal, neural, hormonal and hemodynamic in nature. Activation of these multiple systems--as a result of renin, angiotensin II and the action of circulatory catecholamines--causes the release of norepinephrine vasopressin and aldosterone. These responses contribute to the arteriolar constriction and salt and water retention that promote central pooling with an increase in pre- and afterload of the already failing heart, causing deterioration of the congestive heart failure (CHF). Therapy for this clinical syndrome is aimed at reducing both pre- and afterload with vasodilators, which produce a profoundly favorable effect on left ventricular performances. Beta blocking agents, which inhibit the increased sympathetic mediated vasoconstriction, up-regulate beta receptors and thus restore responsiveness to the failing heart. Inotropic agents, such as digitalis and amrinone/milrinone are reserved for patients with dilated failing heart and impaired systolic function; recently a synthetic atrial natriuretic factor has been developed for potential use in CHF. Ultrafiltration is also used in refractory preoperative CHF with cardiac abnormalities. Neuroendocrine responses to CHF are treated today directly by improving central hemodynamic imbalance in these patients. PMID- 8454457 TI - Prosthetic valve endocarditis due to Listeria. PMID- 8454458 TI - Annual meeting of the Israel Cardiology Society. Tel Aviv, Israel, April 1992. Abstracts. PMID- 8454460 TI - Israeli AIDS numbers relatively low. PMID- 8454459 TI - Medical prayers and oaths in Jewish lore. PMID- 8454461 TI - Testing a theoretical proposition for modeling and role-modeling: basic need and adaptive potential status. AB - The purpose of this research was to test the validity of a propositional statement within the Modeling and Role-Modeling theory and paradigm (Erickson, Tomlin, & Swain, 1988). The Adaptive Potential Assessment Model (APAM) is part of a multidimensional assessment strategy used by nurses to determine ability to mobilize coping resources. This study tested the theoretical proposition that basic need satisfaction and adaptive potential status are directly related. Three study hypotheses were deduced from the identified theoretical proposition. A simple linear relationship between basic need satisfaction and adaptive potential status was not supported. Multidimensional representations of the relationships contained important findings. Understanding more about the relationships between basic need status and adaptive potential will contribute to refining this theory for use in practice. PMID- 8454462 TI - Substance use and anger in mid-life women. AB - The purpose of this research was to examine individual and social network variables that relate to drinking alcohol and utilizing over-the-counter (OTC) medications. The present study sought to expand on the literature by adding modes of anger expression and social network variables as potential explanations of alcohol and OTC use in mid-life women. Secondary analyses were conducted on data from 87 mid-life women who were participating in a longitudinal study of health. Both alcohol and OTC users reported higher anger symptomatology than nonusers and had different profiles in terms of education and age. Social network variables were unrelated to substance use. Implications for intervention strategies and future research were discussed. PMID- 8454463 TI - Effectiveness of a women's mental health treatment program: a pilot study. AB - This exploratory pilot study sought to determine the effectiveness of a Women's Mental Health Treatment Program. This program was offered in a women's unit within a private psychiatric hospital and advertised as a way to help women deal with problems and issues unique to their gender. Twenty-six women responded to a survey questionnaire that explored their quality of life, social support network, ratings of the program, and feelings of self-esteem after discharge. These women were admitted for depression, anxiety attacks, marital problems, and eating disorders. Overall results pointed to the effectiveness of the program as indicated by the women's positive ratings of their current life situation, self esteem, ability to resume work after discharge, and written appreciative comments. The various therapies rated as effective as part of the program treatment package were group therapy, individual therapy, assertiveness training, victim survivor, steps study, and esteem building. PMID- 8454464 TI - Effects of relaxation training, combining imagery, and meditation on the stress level of Chinese nurses working in modern hospitals in Taiwan. AB - The purpose of this study was to test the effectiveness of relaxation training, which was based on the cognitive-behavioral model and specifically focused on helping Chinese registered nurses employed in large teaching hospitals to reduce their work stress in Taiwan, Republic of China. The study design was a pretest posttest control design with two posttest points. The 137 subjects were selected randomly from three first-ranked teaching hospitals. Twenty-three subjects in the experimental group and 23 in the control group from each hospital participated in the study. The treatment of the experimental group consisted of two sessions of relaxation training based on Smith's (1988) cognitive behavioral model of relaxation at weeks 1 and 2, with a follow-up session in the fifth week. The control group had the same sequence of sessions with a presentation by the researcher on theory analysis in nursing. The mean scores on the Nurse Stress Checklist (NSC) and the Chinese General Health Questionnaire (CGHQ) differed significantly between the experimental and control group in posttest 2 at week 5. These results supported the hypotheses that the relaxation training decreased the Chinese nurses' self-reported work stress as measured by NSC and increased the Chinese nurses' self-reported psychophysiologic health as measured by CGHQ. The significant difference on means of the CGHQ in posttest 1 at week 2 showed that the self-reported psychophysiologic health level responded to the relaxation training earlier than to the self-reported work stress level. In the relaxation treatment, duration of practice was an important factor of the effectiveness of the treatment on the dependent variable of NSC. It is suggested that even brief teaching of relaxation techniques may reduce work stress levels and promote a sense of psychophysiologic health in Chinese nurses who are employed in large teaching hospitals in Taiwan. PMID- 8454465 TI - Promoting nursing students' positive attitudes toward providing care for suicidal patients. AB - Nurses may encounter patients who are suicidal in most clinical settings, yet many nurses report a negative attitude toward providing care for these patients. Nursing programs, in which students learn about suicide and develop skills in assessing and intervening with patients who are suicidal, are opportune settings for promoting a positive attitude toward providing care for suicide attempters. An experimental study compared the effectiveness of an interactive teaching strategy known as "structured controversy" with a lecture on promoting a positive attitude. A questionnaire based on Ajzen and Fishbein's (1980) theory of reasoned action was used to measure attitude, and was completed by 51 senior nursing students following a suicide class session. Students who had participated in structured controversy on suicide were significantly more positive on the stress/frustration factor extracted from a scale of attitude items. Students who had listened to the suicide lecture held significantly more positive beliefs about providing care for suicidal patients. Implications for education and practice are discussed. PMID- 8454466 TI - Maternal support and stress response in sexually abused girls ages 6-12. AB - The relationships between maternal support and stress response are examined in this study of sexually abused girls, ages 6-12. Study participants included 20 mother-daughter pairs in which the daughter had been sexually abused, and 50 mother-daughter pairs in which the daughter was not known to have been sexually abused. Both groups were convenience samples. When the variables that significantly differentiated between the two groups (abused, nonabused) were held constant, the relationship between maternal support both as perceived by the mothers (Pr = -.58, p < .02) and as perceived by the daughters (Pr = -.68, p < .003) and stress response (as perceived by the mothers) was significant in the abused group and was not significant in the nonabused group. No significant differences were found in the levels of maternal support and stress response between the two groups when controlling for other stressful life events. However, the abused group had significantly higher levels of stress response overall (F [1, 68] = 2774.56, p < .02) and had significantly more (one and a half times as many) stressful life events (M = 15.10, SD = 6.39) than the nonabused group (M = 10.55, SD = 6.39). PMID- 8454467 TI - Posttranslational modification of beta 141 Leu associated with the beta 75(E19)Leu-->Pro mutation in Hb Atlanta. AB - The recent report of the oxidation of beta 141 Leu in a New Zealand family with Hb Atlanta [ beta 75(E19)Leu-->Pro] prompted us to reinvestigate the original Hb Atlanta case from Georgia. Tryptic peptide maps showed that the modified beta CoT 14 peptide was present together with beta AT-14 in isopropanol precipitates of Hb Atlanta. Amino acid analysis confirmed that beta CoT-14 lacked leucine and mass spectrometry indicated that it had an increased mass of 16 Daltons. These findings support the proposition that the beta 75 Leu-->Pro substitution in the E helix is the direct cause of the beta 141 Leu oxidation. PMID- 8454468 TI - An initiation codon mutation as a cause of beta-thalassemia in a Belgian family. AB - Nine asymptomatic members of a family of Belgian origin, spanning three generations, present typical features of heterozygous beta-thalassemia. Since no mutation was detected with a large panel of oligonucleotide probes, the thalassemia gene was investigated by direct sequencing of DNA segments amplified by the polymerase chain reaction. A T-->C transition was detected in the translation initiation codon (ATG). The mutation, which abolishes an Nco I restriction site, was further confirmed by enzymatic digestion as well as by dot blot hybridization of the amplified products with allele-specific oligonucleotide probes. It produced a beta zero-thalassemia phenotype characterized by marked microcytosis and hypochromia, as well as by an in vitro beta/alpha chain synthesis ratio close to O.5. Search for haplotype linkage showed the mutation to be associated with haplotype IX [- + - + + + +]. PMID- 8454469 TI - Beta-thalassemia mutations in the Portuguese; high frequencies of two alleles in restricted populations. AB - We report the characterization of seven different beta-thalassemia mutations in 131 newly diagnosed Portuguese beta-thalassemia heterozygotes. Methodology included the detection of abnormal fragments by agar gel electrophoresis of PCR amplified DNA fragments after digestion with specific restriction endonucleases, as well as hybridization with synthetic nucleotide probes and sequencing of amplified DNA. Four mutations, including the newly discovered TGG-->TGA change at codon 15, occurred in excess of 10% and accounted for some 90% of the beta thalassemia alleles in this population. The geographical distribution is uneven; the TGG-->TGA mutation at codon 15 was primarily observed in the coastal region north of Lisbon, while the IVS-I-6 (T-->C) mutation was confined to the central part of the country. PMID- 8454470 TI - Usefulness of HPLC methodology for the characterization of combinations of the common beta chain variants Hbs S, C, and O-Arab, and the alpha chain variant Hb G Philadelphia. AB - We have analyzed the blood samples from seven members of two families that contained mixtures of different hemoglobin types due to the simultaneous presence of different beta chain variants and the alpha chain variant Hb G-Philadelphia. The methods used were isoelectrofocusing and cation exchange high performance liquid chromatography for the separation of the hemoglobin components, and reversed phase high performance liquid chromatography for that of the various alpha and beta chains; the chromatographic procedures also provided quantitative data. Application of these fast and simple high performance liquid chromatographic methods greatly aided in defining the different hemoglobinopathies that were present in these persons, including an additional alpha-thalassemia-2 heterozygosity or homozygosity. PMID- 8454471 TI - Characterization of Hb Volga [beta 27(B9)Ala-->Asp] and Hb J-Wenchang-Wuming [alpha 11(A9)Lys-->Gln] in the population of the United States. PMID- 8454472 TI - Frequency of the alpha-thalassemia-2 gene among Nigerian SS patients and its influence on malaria antibody titers. PMID- 8454474 TI - Hb Muskegon [beta 83(EF7)Gly-->Arg]: a new variant found in a family from the U.S. PMID- 8454475 TI - The phylogeny of nine species of the Drosophila obscura group inferred by the banding homologies of the chromosomal regions. IV. Element C. AB - Homologies of the sections of the polytene chromosomes of element C, among several species of the obscura group of the genus Drosophila, were established according to the similarity of their banding patterns. The information gathered was used to construct an unrooted phylogenetic tree based on qualitative criteria. This tree is compared to three other similar trees derived from independent information provided by the study of chromosomal elements B, D and E. The general congruence of the patterns of these trees proves the well-foundedness of this approach. A single exception to this congruence is discussed. Finally a consensus tree, encapsulating information from all chromosomal elements, is presented and its topology is compared to those derived from electrophoretic data. PMID- 8454473 TI - A new screening test for unstable hemoglobins using N-butanol and red blood cells. PMID- 8454476 TI - Remote afterloading brachytherapy for the local control of endobronchial carcinoma. AB - PURPOSE: The study was designed to, (a) standardize endobronchial brachytherapy and, (b) to evaluate the relief of obstructive signs and symptoms. METHODS: Patients with endobronchial carcinoma were treated on a protocol (n = 342) with remote afterloading brachytherapy. Group 1 patients were treated with medium dose rate and received 1000 cGy at 5 mm depth for three fractions (n = 47). Group 2 were treated with high dose rate, 1000 cGy to a 10 mm depth for three fractions (n = 144) and Group 3 received 750 cGy delivered to a 10 mm depth for three fractions (n = 151). Each group was divided into curative, palliative, and recurrent categories. Neodymium yttrium aluminum garnet photoresection was used in 24% of patients prior to brachytherapy. RESULTS: Evaluation consisted of symptom index scoring with weighted responses of hemoptysis 99%, obstructive pneumonia 99%, cough 85%, and dyspnea 86%. Obstruction improvement was 80% overall, curative 87%, palliative 84%, and recurrent 70% of mean pretreatment scores. Survival 10% alive, 88% expired, and 2% lost to follow-up. Cause of death was intrathoracic carcinoma 41%, metastatic carcinoma 38%, intercurrent disease 9%, and unknown cause 13%. Survival from diagnosis and first treatment was, respectively, for curative 10.8 and 9.5 months, palliative 14 and 5.6 months, and recurrent 25.6 and 6.2 months. Significant complications were fatal hemoptysis 7%, and radiation bronchitis and stenosis 11%. CONCLUSION: Endoluminal brachytherapy provides excellent palliation of the endobronchial portion of neoplastic disease. PMID- 8454477 TI - T1-T2 squamous cell carcinoma of the glottic larynx treated with radiotherapy: a multivariate analysis of variables potentially influencing local control. AB - PURPOSE: To examine various parameters that might influence the probability of local control of T1-T2 glottic carcinoma treated with radiotherapy. METHODS AND MATERIALS: Two hundred forty-seven patients with invasive, previously untreated T1-T2 squamous cell carcinoma of the glottic larynx were treated with radiotherapy between May 1977 and December 1989. All patients had a minimum 2 year follow-up. To minimize treatment-related variables, only patients with T1 lesions treated once daily at 225 cGy per fraction and patients with T2 lesions treated once daily at 225 cGy per fraction or twice daily at 120 cGy per fraction were included. Surgical alternative, thickness of the neck at the posterior edge of the lateral fields, vocal cord mobility, anterior commissure involvement, gender, and T stage were evaluated in a multivariate analysis. RESULTS: The 5 year local control rates, calculated by the product-limit method, were T1a, 95%; T1b, 96%; T2a, 87%; and T2b, 76%. The 5-year local control rate for patients with T2 lesions treated with once-daily fractionation was 81% compared with 91% for those who received twice-a-day radiotherapy. For the endpoint of local control with irradiation, the surgical alternative (p = .020) and cord mobility (p = .001) were of independent prognostic significance. CONCLUSION: Of the variables analyzed, only vocal cord mobility and surgical alternative significantly influenced local control. Specifically, anterior commissure involvement and neck thickness did not affect local control. PMID- 8454478 TI - A randomized trial of radiation therapy compared to split course radiation therapy combined with mitomycin C and 5 fluorouracil as initial treatment for advanced laryngeal and hypopharyngeal squamous carcinoma. AB - Two hundred and twelve patients with previously untreated advanced squamous carcinoma of the larynx or hypopharynx were randomized to receive initial treatment with radiotherapy, 50 Gy in 20 fractions in 28 days or split course radiotherapy and concurrent chemotherapy, 25 Gy in 10 fractions in 14 days followed by a 4 week rest and a further 25 Gy in 10 fractions in 14 days starting on day 43; Mitomycin C was given on day 1 and day 43 and 5FU continuous infusions on days 1--4 and days 43--46. Surgery was reserved for persistent or recurrent disease. Two hundred and nine of the 212 patients randomized were included in the analyses. Outcome analyses were performed at a median follow-up interval of 4.4 years. No patients were lost to follow-up. No significant difference was found between the two arms for the end points of local relapse-free rate (p = 0.91), regional relapse-free rate (p = 0.17, adjusted) or overall survival (p = 0.86). Eight-eight patients had attempted surgical resection following radiotherapy failure. The contribution of salvage surgery to overall survival was similar for both arms of the study as was the surgical complication rate. Serious late radiation toxicity was minimal (3% in the RT group, 0% in the radiation therapy plus chemotherapy group). The result of the trial shows no advantage in terms of local control or survival for the experimental treatment arm of split course radiotherapy and concurrent chemotherapy with Mitomycin C and 5 Fluorouracil compared to radiotherapy alone. PMID- 8454479 TI - Squamous cell carcinoma of the head and neck: management after excisional biopsy of a solitary metastatic neck node. AB - PURPOSE: The judiciousness of open biopsy of lymph node mestastases in the neck is controversial. A retrospective review of treatment results at the University of Florida in patients who underwent excisional biopsy of a solitary metastatic neck node followed by radiotherapy was undertaken to determine whether the approach resulted in increased rates of regional and distant recurrence or wound complications. METHODS AND MATERIALS: Between October 1964 and September 1987, 41 patients were referred for radiotherapy after excisional biopsy of a solitary cervical node containing metastatic squamous cell carcinoma from a known mucosal site (19 patients) or unknown primary (22 patients) in the head and neck. None had known gross residual neck disease. The neck stage (based on N stage before surgery or size of the excised node) was unknown in seven patients, N1 in 15 patients, N2A in 18 patients, and N3A in one patient. All patients received radiotherapy to the neck and two had a planned neck dissection after radiotherapy. Doses to the nodal bed ranged from 5485 cGy to 8100 cGy (median, 6675 cGy). RESULTS: The probability of control of neck disease was 95% at both 5 and 10 years. Five-year probability of disease control above the clavicles was 90%. Distant metastasis occurred in 0 of 36 patients whose disease was controlled above the clavicles vs. 3 of 5 patients who suffered failure above the clavicles. CONCLUSION: Excisional biopsy of a solitary neck node followed by radiotherapy produced excellent regional control and no apparent increased rate of distant metastasis. PMID- 8454480 TI - The results of primary radiation therapy in the management of squamous cell carcinoma of the penis. AB - PURPOSE: The outcome of radical external beam radiation therapy for 26 consecutive patients with invasive carcinoma of the penis treated between 1970 and 1985 was assessed to test the efficacy, and side effects of such treatment. METHODS AND MATERIAL: A retrospective review of 26 patients with invasive carcinoma of the penis and 11 patients with carcinoma in-situ of the penis, treated at the Princess Margaret Hospital between 1970 and 1985, was performed. Radiation treatment was delivered using 60Co or 100-250 kv equipment to a dose ranging from 25 Gy in 10 fractions over 2 weeks to 60 Gy in 25 fractions over 5 weeks. The most often used XRT prescription was 50 Gy in 20 fractions over 4 weeks. RESULTS: The 5-year overall actuarial survival for patients with invasive cancers was 62% (+/- 10) and the cause-specific survival was 69% (+/- 9). The control of the primary lesion was 61.5%. Of five patients who progressed after initial radiotherapy, one patient was salvaged by penectomy. Of 11 patients who recurred after initial complete response, three did so in the penis alone and all were successfully salvaged by penectomy. Late complications were recorded in seven patients, two of whom underwent penectomy as a result. All patients with carcinoma in-situ achieved a complete response and, with follow-up ranging from 1 to 14 years, none recurred. CONCLUSION: We conclude that radiation therapy with surgery reserved for the management of local recurrence is an effective first line treatment for patients with carcinoma of the penis. PMID- 8454482 TI - Effect of D,L-alpha-difluoromethylornithine (DFMO) enhanced [3H]putrescine uptake on 9L tumor cell growth and colony forming efficiency. AB - PURPOSE: This study explored the possible use of D,L- alpha difluoromethylornithine (DFMO) to enhance the uptake of [3H] putrescine in order to selectively kill brain tumor cells. METHODS AND MATERIALS: Gliosarcoma cells (9L) were grown for 4 or 20 day periods in monolayer cultures with or without [3H] putrescine and/or DFMO. Cells in culture incubated for 20 days were replated at 4-day intervals. Cells were counted on a Coulter Electronic Particle Counter and percent viability was determined by eosin dye exclusion. Survival of cells with proliferative capacity was assayed by their colony. Forming ability and surviving fraction was calculated. The radioactive counts due to [3H] putrescine were measured in 9L cells and in medium and expressed as cpm/100 cells or cpm/ml, respectively. RESULTS: As previously reported (15), DFMO treatment resulted in termination of cell proliferation that was reversible by the addition of exogenous putrescine. Specifically, after 4 days in culture, cell counts in groups exposed to 10 mM DFMO were 55% of those in control groups and addition of 3 mM putrescine reversed the DFMO effects. Uptake of [3H] putrescine into untreated cells increased in proportion to the amount of exogenous putrescine present during 4 days of culture (range 0.01 nmol to 100 nmol) and the presence of DFMO in the medium enhanced the uptake 9 fold throughout these ranges. At activities greater than 100 cpm/100 cells the cell count was reduced to 23 to 48% of control after 4 days in culture. Extending the treatment to 20 days of incubation increased the killing of 9L cells. During the 20-day incubation, control cells increased from 5 x 10(5) to 13 x 10(12) of which 90% were colony forming cells. Treatment with either 25 microCi [3H] putrescine or 1 mM DFMO for 4 days followed by removal of these agents and incubation for an additional 16 days for a total of 20 days resulted in 31 x 10(8) or 18 x 10(7) colony forming cells, respectively. Combining [3H] putrescine and DFMO treatments during the first 4 days of the 20 day incubation reduced the colony forming cells to 21 x 10(5) (surviving fraction to 67%). When the DFMO treatment was present during the entire 20 days, it became cytotoxic since the colony forming cells were reduced to 35 x 10(3) (surviving fraction was 17%). The combination of the 4-day [3H putrescine and the 20 day DFMO treatments resulted in only 1200 surviving colony forming cells (surviving fraction was only 2%). CONCLUSION: DFMO treatment of 9L cells for 20 days resulted in increased uptake of [3H] putrescine, a 10(10) fold inhibition of colony forming cells and extensive 9L cell killing relative to untreated controls. PMID- 8454484 TI - Short-term morbidity from CT-planned transperineal I-125 prostate implants. AB - PURPOSE: To summarize short-term morbidity and tumor response following transperineal CT-guided I-125 prostate implantation. METHODS AND MATERIALS: Twenty-one patients were treated with CT-based transperineal I-125 prostate implantation between June, 1988 and May, 1990. An average of 75 I-125 seeds were placed, with an average activity of .62 mCi/seed. Symptoms were quantified after interviewing each patient in detail. RESULTS: Nearly all patients developed substantial dysuria, nocturia and frequency from 2-24 weeks following implantation. Urinary symptoms usually resolved within 4-6 months of implantation. The one year actuarial potency rate among 18 patients who were potent prior to implantation was 94%. By 6 months after implantation, 14/17 patients (82%) with Stage B tumors had complete regression of palpable disease. Of 17 patients with Stage A or B tumors who presented with an elevated PSA, 76% returned to the normal range within 6 months of implantation. CONCLUSION: CT guided transperineal prostate implants entail moderate, temporary urinary and rectral morbidity. Short-term tumor responses are encouraging. PMID- 8454483 TI - External beam and intraoperative electron irradiation for locally advanced soft tissue sarcomas. AB - PURPOSE: Intraoperative irradiation with electrons was used in conjunction with external beam irradiation and maximal surgical resection in 20 patients with locally advanced soft tissue sarcomas or desmoids. This manuscript presents results with regard to tolerance of treatment and its impact on tumor control and survival. METHODS AND MATERIALS: Ten patients presented with previously untreated primary sarcomas and 10 at the time of local recurrence (two had recurrent desmoid tumors). Tumor location was retroperitoneal in 19 and in the low anterior neck in one. A partial or gross total resection was performed prior to the external beam or intraoperative component of irradiation in every patient, but all had positive resection margins. Patients received 4500-6000 cGy of fractionated, external beam irradiation and an IORT dose of 1000-2000 cGy. Chemotherapy was given only at the time of disease progression. RESULTS: Fourteen of 20 patients (70%) were alive; 11 (55%) were free of disease (4/10 primary, 7/10 recurrent), but 1 required hemipelvectomy for salvage. Progression within the intraoperative irradiation field was documented in only 1 patient (5%) and within the external beam field in 3/20 (15%). Blood born distant metastasis occurred in 5 patients (25%) and peritoneal seeding in 1 (5%). The distant failure incidence by grade was 1/8 (13%) for Grades 1, 2 and 5/12 (42%) for Grades 3, 4. Only 1 patient (5%) developed a > or = severe neuropathy, and small bowel obstruction requiring exploration also occurred in a single patient. CONCLUSION: In view of acceptable tolerance and the high current rate of local tumor control, in spite of incomplete surgical resections, further evaluation of intraoperative irradiation as a component of treatment is indicated for locally advanced primary and recurrent soft tissue sarcomas. PMID- 8454481 TI - Comparison of 131I- and 90Y-labeled monoclonal antibody 17-1A for treatment of human colon cancer xenografts. AB - The choice of radionuclide remains an important question in clinical radioimmunotherapy. Therefore, a study was initiated, using an in vivo model system, to assess the relative merits of 131I- and 90Y-labeled 17-1A monoclonal antibody as therapeutic agents in the treatment of colon cancer. 131Iodine- and 90Y-labeled 17-1A were assessed in animal therapy trials using athymic nude mice bearing LS174T human colon cancer xenografts. 131Iodine-labeled 17-1A decreased tumor growth in a dose-dependent fashion without lethality. In contrast, the doses of 90Y-labeled 17-1A which were required to produce a significant increase in tumor doubling time also caused marked toxicity. Although similar tumor growth inhibition was produced by 250 microCi 90Y- and 150 microCi 131I-labeled 17-1A, Medical Internal Radiation Dose calculations based on biodistribution data estimated that the dose delivered by 90Y was greater than that delivered by 131I. To investigate this discrepancy, 3-dimensional dose distributions within LS174T tumors were assessed using autoradiography and 3-dimensional calculational techniques. It was found that a greater fraction of the dose was deposited in the tumor after treatment with 131I- compared to 90Y-labeled 17-1A. When the Medical Internal Radiation Dose calculations were adjusted using the 3-dimensional dose distributions, 250 microCi of 90Y- and 150 microCi of 131I-labeled 17-1A were found to deliver similar tumor doses. These studies suggest that 131I-labeled 17 1A is superior to 90Y-labeled 17-1A, since 131I-labeled antibody produced less hematological and animal toxicity and was more effective at inhibiting LS174T tumor growth than 90Y-labeled antibody across the range of radionuclide doses tested. Furthermore, they suggest that it will be necessary to perform 3 dimensional dose calculations in addition to Medical Internal Radiation Dose calculations in order to interpret tumor dosimetry. PMID- 8454485 TI - Local excision and post-operative radiation therapy for rectal carcinoma. AB - PURPOSE: To assess the patterns of failure and outcome following conservative surgery and post-operative radiation therapy for rectal cancer. METHODS AND MATERIALS: Twenty-five patients underwent post-operative radiation therapy (50 Gy in 20 fractions over 4 weeks) following local excision or electrocoagulation for carcinoma of the rectum. None of the patients had palpable residual disease following surgery. Selection factors for post-operative radiation therapy were refusal of a permanent colostomy, excessive operative risk of an abdominal perineal resection and concern regarding local control with conservative surgery alone. RESULTS: Six of 25 patients developed failure at the primary site. There was no lymph node failure. All five patients with primary failure alone underwent abdominal perineal resection and 2 remained free of recurrence. With a median follow-up of 6 years, 20 of 25 patients remained alive and free of disease. There was no apparent influence of age, sex, type of surgery, tumor size, distance of tumor from anal verge, tumor configuration, resection margins, integrity of the resected tissue, depth of invasion, differentiation, presence of lymphatic or vascular channel invasion, radiation dose or field size on local control and survival. One of 15 patients failed locally when the overall treatment time was 30 days or less, whereas 5 of 10 patients developed local failure when the overall treatment time exceeded 30 days. Sixteen of 20 patients in whom cancer did not recur retained normal anorectal function. All four patients with grade 3 early morbidity and the only patient with Grade 3 late morbidity were amongst the group of 13 patients treated with large AP-PA fields (mean: 15 x 19 cm2). CONCLUSION: In selected patients who are at high risk of local recurrence following local excision alone, and who refuse a colostomy or are at high operative risk from radical surgery, post-operative radiation therapy is an alternative to radical surgery. PMID- 8454486 TI - Giant pituitary adenomas: role of radiotherapy. AB - Between 1970 and 1989, 31 patients with a diagnosis of giant pituitary adenoma were referred to the London Regional Cancer Center. Giant pituitary adenoma was defined in terms of extension in excess of 40 mm from the midpoint of the jugum sphenoidale. The diagnosis was made surgically in 30 patients and clinically in one. Tumor extent and dimensions were obtained from operative reports and/or radiological scans computed tomography or magnetic resonance imaging. Mean follow up was 8 years. Initial treatment consisted of surgery alone (4 patients), radiotherapy alone (2 patients) and combined surgery-radiotherapy (25 patients). One patient underwent a needle biopsy for histological confirmation and was grouped with the radiotherapy alone subset. Four of the six patients who received single modality treatment failed initial treatment (three surgery and one radiation). In contrast only 3 of the 25 patients treated with combined surgery post-operative radiotherapy progressed despite the fact that all patients had gross residual disease post-operatively and that 43% of these patients received radiotherapy based on the post-operative rather than the pre-operative tumor extent. With subsequent salvage, overall tumor control amongst the 31 patients was 93.5%. Complications in general were minimal although one acromegalic patient sustained a unilateral internal capsular cerebrovascular accident year post treatment. In summary, combined modality treatment with initial surgical debulking followed by radiotherapy in the dose range of 4500-5000 cGy over 25 fractions yields tumor control rates in giant pituitary adenomas similar to those of smaller pituitary adenomas without undue morbidity. PMID- 8454487 TI - Can pretreatment computed tomography findings predict local control in T3 squamous cell carcinoma of the glottic larynx treated with radiotherapy alone? AB - PURPOSE: To determine if pretreatment computed tomography findings can predict local control in T3 squamous cell carcinoma of the glottic larynx treated with radiotherapy alone. METHODS AND MATERIALS: Twenty-nine patients with previously untreated T3 squamous cell carcinoma of the glottic larynx were treated for cure with radiotherapy alone; all had a minimum 2-year follow-up. High-quality pretreatment computed tomography scans were retrospectively reviewed by a single head and neck radiologist for tumor involvement of various anatomic subsites within the larynx, and total tumor volumes were calculated for 18 of the most recent patients using a computer digitizer. A tumor score was calculated and assigned to each primary lesion depending on the extent of laryngeal spread. RESULTS: A significant decrease in the local control rate was observed for cancers involving the face of the arytenoid (11 of 20 [55%] vs. 9 of 9 [100%]; p = .02), or the paraglottic space at the false vocal cord level (7 of 16 [44%] vs. 13 of 13 [100%]; p not equal to < .01). Tumors assigned a high tumor score (6, 7, or 8) had a significantly decreased rate of local control with radiation therapy when compared with tumors assigned a low tumor score (< or = 5): 1 of 7 (14%) vs. 19 of 22 (86%) (p = .01). Total tumor volume also significantly correlated with the rate of tumor control. For tumors measuring 3.5 cm3 or less, local control was achieved in 11 of 12 patients (92%), whereas for tumors greater than 3.5 cm3, local control was achieved in 2 of 6 patients (33%) (p = .02). CONCLUSION: Pretreatment computed tomography scans can contribute significantly to the treatment decision for patients with T3 glottic carcinoma and can define a subset of patients with an excellent chance of being cured with preservation of a functional larynx after treatment with radiotherapy alone. PMID- 8454489 TI - Use of transputers for real time dose calculation and presentation for three dimensional radiation treatment planning. AB - PURPOSE: Real-time 3-dimensional dose calculation will allow display of isodose contours and other metrics for a planner to assess plan effectiveness during plan development, facilitating optimization. METHODS AND MATERIALS: Parallel processing provides an effective means to calculate 3-dimensional dose distribution in real-time while plan parameters are being chosen and adjusted. An array of 20 transputers and a high performance graphics workstation have demonstrated the feasibility of real-time 3-dimensional beam parameter specification, dose calculation, and dose-distribution presentation for evaluation. A mesh connected set of processors using surface processors to generate and terminate rays, and ray processors to calculate ray attenuation and dose distribution has been developed to efficiently utilize large numbers of processors and provide good load sharing, even for small beams that intersect only a small part of the volume. RESULTS: Our feasibility study has calculated dose distribution by the Effective Path Length method in about one second per beam for a treatment volume of 56,400 voxels. We expect to reduce the total time for computation, communication, and display, with even larger volumes, to less than one second. The number of processors can easily be increased for larger treatment volumes or more accurate and computation-intensive dose-calculation algorithms. Transputers provide an elegant and economical method for harnessing up to hundreds of powerful general-purpose processors for computational tasks including dose calculation and isodose contour generation. The same distributed memory parallel-processing configuration is also suitable for calculation of isodose contours and dose-volume histograms for plan evaluation, automatic calculation of apertures and filters as beam parameters are manipulated, and more accurate dose calculation algorithms that incorporate the effects of scatter. CONCLUSION: Parallel processors can efficiently provide real-time calculation of the information necessary to evaluate treatment plans as they are developed allowing the planner to optimize the plan based on dose distribution and its effects on tumor control and complications. PMID- 8454488 TI - The effect of radiation on normal human CNS as detected by NMR spectroscopy. AB - In a prospective study, proton (1H) and phosphorus (31P) nuclear magnetic resonance spectroscopy were used to search for effects of brain tumor radiotherapy on normal human central nervous system. Phosphorus spectroscopy data at 1.5 T seems to suggest that any radiation induced damage that may occur as a result of therapeutic brain irradiation, does not alter the relative concentrations of phosphorus metabolites or the intracellular pH beyond the limits of normal variation (approximately +/- 20%). Proton spectroscopy, on the other hand, detects post radiation changes in the ratios of certain nuclear magnetic resonance visible metabolites following radiotherapy, particularly choline/N-acetylaspartate, and especially in regions of brain receiving high doses of radiation. Such changes may be indicative of the release of membrane bound choline during radiation induced demyelination of brain. Of interest, we have found elevated metabolite ratios of 31P in normal central nervous system prior to radiotherapy, which persisted throughout the time span of the study in both the ipsilateral and contralateral cerebral hemispheres. PMID- 8454490 TI - Implication of uterine configuration on dosimetry to point A using the Amersham afterloading system. AB - Ninety-four biopsy-proven cases of cervix carcinoma who underwent brachytherapy with the flexible Amersham afterloading system are examined in this study. The uterine configuration showed a wide range with respect to the length, angle of version (indicated by angle alpha) and the degree of right or left shift of the midline at the internal os (indicated by angle beta). The manufacturers of the afterloading system have given certain precalculated dose rates to A which they derived from computer calculations for the various configurations of the system, for a particular loading strength of the Caesium 137 source trains, and for a particular range of angle alpha and beta. The study involves mathematical calculations of point A dose rates using post application radiographs, and a mean value of point A dose rate is derived to compare with other variables. A distortion of the uterus in the form of flexion (as opposed to version), resulting in bending of the uterine tandem is noted in 3 cases. There are 22% of cases with gross degree of retroversion (angle alpha more than 180 degrees) for which the precalculated tables are lacking. The angle beta, however, is in the normal range for all the cases but one. Nineteen cases (20.2%) showed point A dose rates which are beyond the specified dose rates of the manufacturers. Analysis of these 19 cases showed 6 cases with angle alpha more than 180 degrees, eight cases with more than a 10 degrees shift of the uterus to right or left of midline (angle beta) and the rest five cases have fairly normal values of these angles. Analysis of these five cases showed that three of them showed more than 8 CGy/hr difference in dose rates to individual points A right and left. An undue curvature of the uterine tandem to one side in the distal half, with a straight proximal half (near the anterior flange) is noted in these three cases. The angle alpha and beta are normal here since the nearest 2 cm of uterine tandem to the anterior flange is straight, but the distal end lying in a closer position to one side, contributed more dose to point A of that side. This factor of flexion might have resulted both in contributing to a difference in dose rates to points A (Right and Left), as well as undue difference in mean point A dose rates beyond the specified accuracy limits of the manufacturers.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8454491 TI - Measured dose to ovaries and testes from Hodgkin's fields and determination of genetically significant dose. AB - PURPOSE: To determine the genetically significant dose from therapeutic radiation exposure with Hodgkin's fields by estimating the doses to ovaries and testes. MATERIALS AND METHODS: Phantom measurements were performed to verify estimated doses to ovaries and testes from Hodgkin's fields. Thermoluminescent LiF dosimeters (TLD-100) of 1 x 3 x 3 mm3 dimensions were embedded in phantoms and exposed to standard mantle and paraaortic fields using Co-60, 4 MV, 6 MV, and 10 MV photon beams. RESULTS: Our results show that measured doses to ovaries and testes are about two to five times higher than the corresponding graphically estimated doses for Co-60 and 4 MVX photon beams as depicted in ICRP publication 44. In addition, the measured doses to ovaries and testes are about 30% to 65% lower for 10 MV photon beams than for their corresponding Co-60 photon beams. CONCLUSION: The genetically significant dose from Hodgkin's treatment (less than 0.01 mSv) adds about 4% to the genetically significant dose contribution to medical procedures and adds less than 1% to the genetically significant dose from all sources. Therefore, the consequence to society is considered to be very small. The consequences for the individual patient are, likewise, small. PMID- 8454492 TI - Response to editorial by Dr. Robert Kagan. PMID- 8454493 TI - Response to Dr. Dewhirst. PMID- 8454494 TI - Trental (pentoxifylline) relieves pain from postradiation fibrosis. PMID- 8454495 TI - Where to get blood donors? PMID- 8454496 TI - Another case of gastric perforation associated with administration of ibuprofen in a dog. PMID- 8454497 TI - Migration of parasite captures parasitologists' attention. PMID- 8454499 TI - Zoo and wildlife veterinarians examine their role in conservation. PMID- 8454498 TI - Military veterinarians assist in hurricane relief effort. PMID- 8454500 TI - Preharvest food safety an international concern. PMID- 8454501 TI - "Proud to be a veterinarian in the USA". PMID- 8454502 TI - Application of behavior therapy techniques to the treatment of obesity in companion animals. PMID- 8454504 TI - Opportunities for veterinarians in aquaculture. PMID- 8454503 TI - Veterinarians and wildlife. PMID- 8454505 TI - Comparison of intradermal allergy test and enzyme-linked immunosorbent assay in dogs with allergic skin disease. AB - Results of an ELISA for allergen-specific IgE were compared with results of an intradermal (ID) allergy test in 5 clinically normal dogs and 36 dogs referred for evaluation of allergic dermatitis. The ELISA had a sensitivity of 100% and a specificity of 0%. Agreement between ID allergy test and ELISA for positive and negative results ranged from 44 to 56% for pollens, 39% for house dust/dust mite, 22% for fungi, and 54% for fleas. Agreement between ID allergy test and ELISA scores for all pollens was only 10% greater than that expected by chance alone, and a kappa value of 0.17 confirmed poor test agreement. The greatest disparity in results was seen in dogs with negative ID and positive ELISA results. Median ELISA absorbance values for 15 groups of related allergens were compared in 4 groups of dogs: clinically normal dogs, atopic dogs with positive ID reactivity, suspected atopic dogs with negative ID reactivity, and flea-allergic dogs. There was no significant difference in median ELISA values between clinically normal dogs and flea-allergic dogs, or clinically normal dogs and atopic dogs for any allergen group. Although the ELISA absorbance value for fungal antigens was significantly higher in dogs suspected of being atopic than in clinically normal dogs, there was no significant difference in median ELISA values for any other allergen group. These findings suggested the disparity between ID allergy test and ELISA results was primarily attributable to false-positive ELISA reactions rather than greater ELISA sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454506 TI - Development of chronic renal disease in cats fed a commercial diet. AB - Chronic renal failure was observed in 10 young adult client-owned cats that had been fed 1 commercial cat food exclusively since weaning. The diet contained 40% protein and 0.32% potassium on a dry matter basis, and phosphoric acid was added during production. We attempted to determine whether exclusive feeding of this diet would induce clinical and laboratory evidence of renal dysfunction in clinically normal adult cats. Over a 2-year study, 3 of 9 of these cats developed clinical and laboratory evidence of renal dysfunction and renal lesions. Two additional cats developed renal lesions, but had normal laboratory values. The renal lesions consisted of lymphoplasmacytic interstitial nephritis and interstitial fibrosis. We concluded that chronic renal disease may develop in clinically normal adult cats fed diets high in protein and acid content, but marginally replete in potassium. PMID- 8454507 TI - Antimicrobial-resistant Salmonella spp isolated from healthy broiler chickens after slaughter. AB - Of 105 Salmonella organisms of any serotype selected from a sample of 1,824 serotyped salmonellae isolated during a nationwide bacteriologic survey of healthy broiler chickens after slaughter, 60 (57%) were resistant to 1 or more antimicrobial agents and 47 (45%) were resistant to 2 or more agents. Highest resistance was to tetracycline (45%), streptomycin (41%), sulfisoxazole (19%), gentamicin (10%), and trimethoprim/sulfamethoxazole (8%). Additional isolates of S typhimurium, heidelberg, agona, and enteritidis were selected from the sample of 1,824 isolates for testing because of the high frequency with which these 4 serotypes are isolated from human patients. The highest frequency of resistance among 104 isolates of S heidelberg, 92 isolates of S typhimurium, and 30 isolates of S agona was to streptomycin (33 to 57%), sulfisoxazole (33 to 50%), tetracycline (26 to 50%), and gentamicin (13 to 40%); 51 to 63% of these isolates were resistant to 1 or more agents and 37 to 59% were resistant to 2 or more agents. Resistance to ampicillin among these 3 serotypes was uncommon (0 to 4%). In contrast, 15 of 19 tested isolates (79%) of S enteritidis were resistant to ampicillin and 13 of the 19 isolates (68%) were resistant only to ampicillin. This pattern of resistance was associated with a specific bacteriophage type and indicated the potential role of bacterial clones in determining the frequency and patterns of antimicrobial resistance in populations of broiler chickens. Resistance to gentamicin and trimethoprim/sulfamethoxazole was higher than that previously reported and is of public health concern because of the frequency with which these drugs are used to treat bacterial infections in human patients. PMID- 8454508 TI - Focal metatarsal fistulas in five dogs. AB - Focal metatarsal fistulas were identified in 5 young adult German Shepherd Dogs or dogs of similar breeding. A specific cause was not identified when biopsy specimens for culture and histologic examination were evaluated. Corticosteroid treatment was beneficial for some lesions. The dogs did not have other dermatologic diseases, and the clinical course, although chronic, was generally benign. PMID- 8454510 TI - Patent ductus arteriosus and pulmonary hypertension in related Pembroke Welsh corgis. AB - Patent ductus arteriosus (PDA) and pulmonary hypertension were diagnosed in 5 related 12- to 24-week-old Pembroke Welsh Corgi dogs. A ductus diverticulum and small PDA were diagnosed in the pups' sire. Multiple factors likely contribute to the early development of pulmonary hypertension, including pulmonary hyperperfusion, genetic predisposition, and atmospheric pressure. The dogs of this report had a strong genetic predisposition to PDA, had large-diameter PDA associated with pulmonary hyperperfusion, and lived at altitudes of 5,000 to 7,000 feet above sea level. This combination of factors likely had an additive influence on the pulmonary vasculature, resulting in accelerated development of pulmonary hypertension in these dogs. Early recognition and treatment of PDA is critical in this setting before the development of severe pulmonary hypertension and uncorrectable disease. PMID- 8454509 TI - Tail chasing in a bull terrier. AB - A Bull Terrier that was continuously chasing its tail was examined clinically, electroencephalographically, and by computed tomography of the head. The dog was also given test treatments with an anticonvulsant (diazepam) and a pure opioid antagonist (naloxone). The dog appeared to be hysterical and dissociated from its surroundings. Electroencephalography revealed a seizure pattern that was most marked over the temporal lobe, and computed tomography revealed mild hydrocephalus. Diazepam effectively controlled tail chasing, whereas naloxone did not. The dog was discharged on anticonvulsant therapy but subsequently had to be euthanatized when aggression developed. Results of examination and treatment have led the investigators to propose a hereditary mechanism for tail chasing, perhaps related to zinc malabsorption. PMID- 8454511 TI - Repair of a proximal metatarsal Salter type-II fracture in a foal. AB - Bilateral radiographically persistent proximal third metatarsal physes and concurrent cuboidal bone immaturity were identified in a foal. Repair of a Salter type-II fracture of the left proximal third metatarsal physis was accomplished by use of lag screw fixation. A 6-day-old Arabian foal, intended for use as a show horse, was referred because of severe unilateral hind limb lameness and valgus deformity. A Salter type-II fracture of the proximal portion of the third metacarpal bone was identified radiographically and repaired by use of cancellous lag screws. The fractured limb was further supported with a modified Robert Jones bandage and fiberglass tube cast. Eight weeks after surgery, the colt was sound at a trot and had minimal valgus deformity. At this time, radiography revealed healing of the fracture and implants were removed. Six months after fracture repair, the outcome was considered successful on the basis of a desirable cosmetic result and no detectable lameness at a trot. The proximal third metatarsal physis is generally not radiographically visible in the neonate. This report describes the identification and successful repair of a fracture involving this persistent physis. Other sites of skeletal immaturity were also identified, and should be considered in the evaluation and management of unusual physeal fractures. PMID- 8454512 TI - Duodenal leiomyoma associated with colic in a two-year-old horse. AB - A 2-year-old horse with signs of colic, reflux on nasogastric intubation, and large colon distention on transrectal palpation was found to have a leiomyoma involving the duodenum. The mass was excised without penetration of the lumen of the small intestine, and the horse recovered without complications. PMID- 8454513 TI - Use of ventral cervical stabilization for treatment of a suspected articular facet fracture in a horse. AB - A 3-year-old Thoroughbred filly examined because of poor performance after a fall was found to be ataxic. Radiography revealed a linear defect in the right dorsal cranial articular facet of the fifth cervical vertebra. The defect was thought to be a fracture or a developmental defect. Arthrodesis and stabilization were achieved by ventral implantation of a Bagby basket in the articulation between the fourth and fifth cervical vertebrae. The ataxia resolved within 4 months, and the filly was able to resume full race training. PMID- 8454514 TI - Incarceration of the large colon in the gastrosplenic ligament of a horse. AB - Incarceration of the large colon through a rent in the gastrosplenic ligament of a horse was surgically corrected via ventral midline celiotomy. Clinical signs were similar to those in other horses with nonstrangulating large colon disorders. Diagnosis of large colon incarceration in the gastrosplenic ligament was determined by surgical abdominal exploration. The findings of medial deviation of the spleen, location of the large colon lateral to the stomach and caudolateral to the spleen, and caudocraniad passage of the large colon through the gastrosplenic ligament are similar to findings in horses with small intestinal incarcerations in the gastrosplenic ligament. Correction was facilitated by performing a pelvic flexure colotomy and evacuating colonic contents prior to returning the large colon through the rent to its normal anatomic position. PMID- 8454516 TI - Summer pasture-associated obstructive pulmonary disease in horses: 21 cases (1983 1991). AB - Medical records of 21 horses with summer pasture-associated obstructive pulmonary disease were reviewed, and history, signalment, clinical signs, radiographic signs, clinicopathologic data, and therapeutic response were determined. Most affected horses were used as pleasure horses, and for the most part, remained at pasture when not in use. The mean age (+/- SD) was 13.7 +/- 3.6 years. Clinical signs included intermittent nasal discharge, cough, tachypnea, labored expiratory effort, and crackles and wheezes on auscultation. Radiography frequently revealed interstitial patterns in the lung fields; in horses with chronic disease, pulmonary overinflation was evident. Hemogram was usually normal, and transtracheal wash fluid was characterized by nondegenerate neutrophils. PMID- 8454515 TI - Episodic scrotal mutilation with concurrent bilateral sperm granuloma in a dog. AB - Bilateral sperm granuloma with diffuse spermatocele was found to be the cause of infertility in a young Golden Retriever. Anamnesis indicated that the dog had intermittent episodes of self-inflicted ulcerative scrotal dermatitis, beginning when it was 4 to 5 months old and regardless of season or environment. A complete breeding soundness examination produced consistently azoospermic ejaculates in the presence of bilaterally firm, distinct swellings of the epididymides. Because of the poor reproductive prognosis, the owner requested castration and scrotal ablation. Although scrotal trauma was initially thought to be associated with the onset of sperm granuloma formation, evaluation of the history and physical examination and laboratory findings indicated that a bilateral congenital anomaly was the most likely cause of infertility. PMID- 8454517 TI - Idiopathic immune-mediated hemolytic anemia in dogs: 42 cases (1986-1990) AB - Forty-two cases of Coombs' positive or agglutinating immune-mediated hemolytic anemia (IMHA) in dogs were reviewed. Dogs ranged in age from 1 to 13 years, with a mean age of 6.4 +/- 3.4 years. The majority of dogs (74%) tested positive for IgG antibodies without complement. Spherocytosis was seen in 67% of the dogs, but hemoglobinemia and hemoglobinuria were found in only 10%. Marked bilirubinuria was found in all the dogs. A significant seasonal incidence was observed, with 40% of all cases diagnosed during the months of May and June. Severe anemia, with PCV < or = 20% was observed in 37 dogs (88%). Sixteen dogs (38%) had moderate to severe reticulocytosis and 12 dogs (29%) had mild reticulocytosis. Thus, the absence of reticulocytosis should not be used to rule out a diagnosis of IMHA. Concomitant mild to severe thrombocytopenia was observed in 28 dogs (67%). A mortality of 29% was observed during hospitalization. Risk of death was significantly increased in dogs without marked reticulocytosis, those with lower PCV, and dogs with serum bilirubin concentrations > or = 10 mg/dl. In severe cases of IMHA, rapid and aggressive supportive therapy is required. PMID- 8454518 TI - Hyperadrenocorticism caused by bilateral adrenocortical neoplasia in dogs: four cases (1983-1988). AB - Hyperadrenocorticism caused by bilateral adrenocortical neoplasia was diagnosed in 4 dogs. Three dogs had bilateral adrenocortical adenomas, and 1 dog had bilateral adrenocortical carcinomas. The history, physical findings, clinicopathologic abnormalities, and results of ACTH stimulation and low-dose dexamethasone suppression tests were compatible with diagnosis of hyperadrenocorticism. Adrenocortical neoplasia was differentiated from pituitary dependent hyperadrenocorticism on the basis of a combination of test results, including lack of suppression of plasma cortisol after being given a high dose dexamethasone (n = 4), undetectable (< 20 pg/ml) plasma endogenous ACTH concentration (n = 4), identification of a single mineralized adrenal mass by abdominal radiography (n = 2) and abdominal ultrasonography (n = 1), and identification of bilateral nonmineralized adrenal masses by ultrasonography (n = 1). A left adrenal mass was excised from 1 dog. Clinical signs persisted and administration of mitotane was initiated. One dog was treated only with mitotane. Treatment with ketoconazole was attempted in 2 dogs. All dogs died or were euthanatized because of persistent hyperadrenocorticism. Necropsy and histologic evaluation of the pituitary and adrenal tissue confirmed bilateral adrenocortical neoplasia in all dogs. Bilateral adrenocortical neoplasia should be considered as an uncommon, but possible, cause of bilaterally large adrenal glands in dogs with hyperadrenocorticism. PMID- 8454519 TI - What is your diagnosis? Four spines and 3 normal skulls of fetuses were visible. PMID- 8454520 TI - What is your diagnosis? Spherical mass in the left dorsal quadrant of the abdomen. PMID- 8454521 TI - North Americans meet Danes: culture shock strikes. PMID- 8454522 TI - Weighing community and individual needs: clinical testing. PMID- 8454523 TI - Body temperature and diurnal type in women with seasonal affective disorder. AB - Body temperature rhythms and diurnal type were explored in female controls and women with seasonal affective disorder (SAD) before and after phototherapy. Women with SAD reported being more like evening types than did controls. Morning phototherapy advanced the body temperature rhythms of women with SAD, and shifted their morningness/eveningness scores toward the morning end of the continuum. The implications of these results for our understanding of both SAD and depression in women are discussed. PMID- 8454524 TI - Virginity and tampons: the beginner myth as a case of alteration. AB - Using an inductive analytical approach to the portrayal of menstruating women in menstrual product advertisements, we discovered that tampon advertisements directed to adolescents provide a unique case of myth alteration. The beginner myth contends that tampon use by young women threatens virginity. With considerable deftness, the tampon advertisements we analyzed addressed the beginner myth, both dispelling the myth and at the same time retaining it to the degree that it sustained the need for specialized tampons. PMID- 8454525 TI - The Adolescent Menstrual Attitude Questionnaire, Part I: Scale construction. AB - A valid, reliable, and age-appropriate instrument to measure adolescent responses to menarche was constructed. The Adolescent Menstrual Attitude Questionnaire is a 5-point Likert scale (with six sub-scales) with versions for pre- and postmenarcheal girls. Scale development included (a) content validation, (b) testing (with 860 premenarcheal and 1,013 postmenarcheal girls), (c) discriminant analysis (to identify items unique to the pre- and postmenarcheal experience, (d) construct validity using principal component factor analysis, and (e) reliability analysis. Development of the scale revealed that on some dimensions, the attitudes of premenarcheal girls were qualitatively different from those of postmenarcheal girls. Thus, the final versions of the Adolescent Menstrual Attitude Questionnaire consist of 58 items each, with 43 common items, 4 common items that load on different subscales, and 11 unique items. Reliabilities (r) are .91 and .90 for the pre- and postmenarcheal versions, respectively. PMID- 8454526 TI - The Adolescent Menstrual Attitude Questionnaire, Part II: Normative scores. AB - Results obtained from administering the Adolescent Menstrual Attitude Questionnaire to 860 pre- and 1,013 postmenarcheal girls from 49 randomly selected schools in a large western Canadian city are reported. Scores obtained for both the pre- and the postmenarcheal versions of the total scale and the subscales are presented by age and by grade. In addition, for postmenarcheal girls, the self-report of menstrual symptoms gives insight into the prevalence of symptoms and the perception of symptom severity. Correlations between self reported symptoms with the Menstrual Symptoms subscale score and the total scale score add validity to the scale. These data may be used by clinicians for comparison when administering the scale to individuals or to groups. PMID- 8454527 TI - Health care professionals' perceptions of seriously ill women. AB - Physicians, psychologists, and nurses read one of four vignettes describing a woman who had received one of four diagnoses--breast cancer, lung cancer, heart attack, or severe burn--and indicated on the Profile of Mood States (McNair, Lorr, & Droppleman, 1971) how they perceived the woman had been feeling during the past week. They then answered 10 questions about the woman's recovery and about their own anticipated behaviors while interacting with her. A number of differences emerged between professional groups in terms of their expectations for patients regardless of diagnosis. In addition, respondents held different emotional expectations for the patient, based solely on her diagnosis. These results support the need for training health care professionals to recognize psychological distress in, and appropriately refer, seriously ill women. PMID- 8454528 TI - Reproductive technologies and court-ordered obstetrical interventions: the need for a feminist voice in nursing. AB - As the developments in and increasing use of reproductive technologies continue and as court-ordered obstetrical interventions occur, questions regarding nurses' roles in these developments become increasingly important. In this article, I identify a number of issues surrounding these developments in reproductive health care and examine how nurses have dealt with these issues. I also attempt to encourage nurses to examine and discuss these developments from a critical, woman centered perspective. A review of articles from the nursing literature (1985 1990) grouped together on the basis of the concerns identified, approach used, or subjects studied is presented. The majority of researchers view reproductive technologies as either acceptable or as requiring legislation and control. Few researchers in nursing have identified concerns about reproductive technologies or court-ordered obstetrical interventions from a feminist perspective. It is crucial that questions be raised about the underlying assumptions of these measures and about their implications for women as patients and for nurses as practitioners, women, and promoters of health. Otherwise, nurses may be supporting technologies and other measures that harm women and nursing itself. PMID- 8454529 TI - Role perceptions of divorcing parents. AB - Using interview data from a convenience sample of 101 divorcing parents, we examined the gender roles of parents during the transition from marriage to divorce. We found that the women, who most often initiated divorce, were changing their roles and that this was related to marital dissatisfactions. Factor analysis indicated that real differences existed in how mothers and fathers perceived the co-parental relationship. Mothers saw the relationship as supportive at times and conflictual at times. Fathers tended to view the relationship as helpful only if it did not contain conflict. Improved communication in the coparental relationship after divorce seemed to be related to changes in traditional female and male roles. PMID- 8454530 TI - Factors that influence fathers' participation in child care. AB - Using the social address model, we examined demographic factors that influence fathers' participation in child care by comparing trends in two samples: (a) 139 professional women and their spouses and (b) a heterogeneous group of 214 homemakers and employed women and their spouses. Results support previous observations that fathers are more likely to engage in play activities with their children than perform any other type of child care. Mothers continue to be primarily responsible for child care, regardless of their employment status. Parental education level was the most consistent predictor of father participation in both samples. The findings are discussed in terms of moving beyond intrafamily variables as predictors of child care participation to the larger contexts of gender and power. PMID- 8454532 TI - Interaction of whole cottonseed and supplemental fat on digestive function in cattle. AB - Four Holstein steers (155 kg) with "T" cannulas in the rumen and proximal duodenum were used in a 4 x 4 Latin square design experiment to evaluate the interaction of whole cottonseed (WC) and yellow grease (YG) on digestive function. Four treatments were compared: 1) 0% YG, 0% WC; 2) 5% YG, 0% WC; 3) 0% YG, 20% WC, and 4) 5% YG, 20% WC. The YG and WC were substituted for steam-flaked corn in an 80% concentrate growing-finishing diet. Both YG and WC decreased ruminal OM digestion (P < .01). However, the effects were not additive (interaction, P < .05). When YG was added to the control diet ruminal OM digestion was decreased by 6.9%. In contrast, when YG and WC were added to the control diet the decrease was 24.0%. This interaction was also apparent (P < .05) in ruminal digestion of feed N and starch. Total tract digestion of OM was decreased (P < .01) with WC and YG supplementation, although, like ruminal digestion, the effects were nonadditive (P < .05). In the absence of WC, YG had little influence (.8%) on OM digestion. However, in the presence of WC, YG decreased total tract OM digestion 5.7%. This interaction was also manifest (P < .05) in total tract digestion of ADF and GE. Although there was some compensation with respect to methane energy loss, the ME (megacalories/kilogram) of WC was 20% lower when fed in combination with YG. The degree of ruminal biohydrogenation of unsaturated fatty acids was high for both WC and YG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454531 TI - Tissue equilibration and subcellular distribution of vitamin E relative to myoglobin and lipid oxidation in displayed beef. AB - Supplementary alpha-tocopheryl acetate (vitamin E) was fed to provide none (E0), 2,000 IU/d (E2000), 5.8 IU/kg live weight (E5.8), or 8.6 IU/kg live weight (E8.6) to steers that were individually fed mainly a corn diet. Three steers were placed on each of 10 treatments: E0, E2000, E5.8, E5.8 to d 126 then E0 to d 266, E0 to d 126 then E5.8 to d 266, E8.6, grazing followed by either E0 or E8.6 all with Holstein steers; and E0 and E2000 with crossbred beef steers. During the last 100 d, vitamin E consumption (International Units/day) averaged 96 for E0, 1,840 for E2000, 2,520 for E5.8, and 3,610 for E8.6. Concentrations of alpha-tocopherol in plasma and in liver and longissimus lumborum biopsy samples obtained every 42 d were elevated (P < .01) by vitamin E supplementation. Tissue saturation was approached at these vitamin E intakes causing similar incorporation of alpha tocopherol with both per day and per BW supplementation strategies. Maximum accretion or depletion of alpha-tocopherol in plasma and liver occurred before 42 d, but accretion required 120 d and depletion required 180 d in longissimus lumborum. Vitamin E supplementation elevated (P < .01) concentrations of alpha tocopherol in liver, lung, subcutaneous fat, omental fat, perirenal fat, kidney, diaphragm, spinal cord, longissimus lumborum, and plasma at slaughter with maximum accretion achieved (P < .01) in lung, subcutaneous fat, kidney, diaphragm, and spinal cord. Depletion was not achieved in longissimus lumborum and spinal cord (P < .01), subcutaneous fat (P < .06), and perirenal fat (P < .08) within 140 d. Vitamin E inhibited (P < .01) oxidation at the surface and center of longissimus lumborum steaks displayed for 19 d. Lipid oxidation occurred throughout E0 steaks, but metmyoglobin accumulation occurred more rapidly (P < .01) on the surface than in the center. Myoglobin and lipid oxidation were not concurrent events. Supplementation with vitamin E increased (P < .01) alpha-tocopherol concentrations in longissimus lumborum fractions (mitochondria, microsome, cytoplasm, connective, and remainder) but, except for connective tissue, the proportional distribution of total longissimus lumborum alpha-tocopherol was not affected (P > .1) by vitamin E supplementation. Vitamin E supplementation for at least 44 d at 1,300 IU/d is expected to incorporate adequate amounts of alpha-tocopherol into muscle (3.3 micrograms/g for longissimus lumborum) to produce beef with extended color and lipid stability. PMID- 8454533 TI - Bioavailability of zinc in ground beef. AB - Based on zinc uptake in chick tibia, Zn bioavailability in cooked ground beef was equal to that of Zn in an inorganic standard (ZnSO4), whether Zn supplements were added to a soy-concentrate diet containing phytate or to a phytate-free egg-white diet. With both diet types, total tibia Zn was a linear (P < .01) function of supplemental Zn intake from ZnSO4, but the slope of the linear regression line was twice as great for the egg-white diet as for the soy-concentrate diet that contained phytate. At 10 mg/kg of supplemental Zn, freeze-dried ground beef produced the same tibia Zn concentration (and total Zn content) as that obtained with ZnSO4. The results suggest that the relative bioavailability of Zn in cooked ground beef is as great as that in ZnSO4, whether consumed in diets with or in those without phytate. PMID- 8454534 TI - Bioavailability of calcium in sun-cured alfalfa meal and effect of dietary calcium concentration on bone and plasma characteristics during two phases of gestation in gilts. AB - A study was conducted with gravid gilts to determine the bioavailability of Ca in sun-cured alfalfa meal (AM) and the effect of dietary Ca concentration on bone and blood characteristics during two phases of gestation. Two Ca sources (AM and CaCO3), three dietary concentrations of Ca (50, 75, and 100% of the NRC requirement), and two gestation phases (55 and 105 d) were used in a 2 x 3 x 2 factorial arrangement in a randomized design with five replications (60 gravid gilts). Response criteria were as follows: 1) plasma Ca, P, and alkaline phosphatase (AKP) measured at the onset and at 25-d intervals and 2) metacarpal (MC) and metatarsal (MT) bone breaking strength (kilograms), ash content (percentage), density (grams/cubic centimeter), and ash density (grams of ash/cubic centimeter) at the conclusion of the experiment. Plasma Ca, P, and AKP concentrations were similar between Ca sources. Because the response between Ca sources was similar, the data were pooled among sources. There was a linear decline in plasma P and AKP (P < or = .05) as dietary Ca concentration increased. As gestation progressed from 0 to 100 d, there was a decline (P < .05) in plasma Ca and P. There were no differences in bone breaking strength and ash between Ca sources in either the MC or MT. No differences in bone strength between gestation phases occurred. A gestation phase x dietary Ca concentration interaction (P < .05) was observed for bone ash in both bones.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454537 TI - Effect of hyperalimentation on body composition in swine. AB - Fifty growing pigs were used in two experiments to evaluate the effects of cannulation and hyperalimentation on performance and body composition responses. Surgical implantation of a cannula into the greater curvature of the stomach and subsequent management associated with maintenance of the cannula did not result in a reduction (P > .05) of voluntary feed intake. Cannulation did not negatively affect gain (P > .05). Over the entire trial, feed efficiency was not changed by cannulation (P > .05). Cannulation itself did not affect protein or fat deposition (P > .05) in the carcass. Hyperalimentation to approximately 120% of control intake resulted in increased daily gain (P < .05) and similar feed efficiency (P > .05) compared with that of control animals. Hyperalimentation decreased protein deposition (P < .05) and tended to increase fat deposition. PMID- 8454536 TI - Tryptophan requirement of pigs in the weight category 10 to 20 kilograms. AB - Experiments were conducted to determine the tryptophan (Trp) requirement of 10- to 20-kg pigs. A Trp-deficient experimental diet (.11% total Trp, 18% CP, 3,320 kcal of ME/kg) was composed of corn, feather meal, corn gluten meal, soybean meal, and dried whey. True digestibility of Trp in the experimental diet was 70% (.077% digestible Trp) as established in a digestibility assay that involved cecectomized, adult cockerels (Exp. 1). An initial pig study (Exp. 2) verified that the experimental basal diet, when fortified with sufficient L-Trp, was capable of producing growth rate and feed efficiency similar to that of pigs fed a conventional corn-soybean meal-dried whey diet (18% CP, 3,320 kcal of ME/kg). In Exp. 3, crossbred pigs with an average BW of 10.9 kg were fed the Trp deficient basal diet supplemented with 0, .015, .030, .045, .060, and .075% L Trp. In Exp. 4, crossbred pigs that averaged 9.5 kg were fed the basal diet fortified with .030, .045, .060, and .075% L-Trp. By examining the data from Exp. 3 and 4 together, the digestible Trp requirement for maximum daily weight gain was estimated to be .14% of the diet. Assuming an 88% true digestibility of Trp in commercial diets based on corn and soybean meal (calculated from published data), the total Trp required in practice would be .16% (.89% of the dietary protein). PMID- 8454535 TI - The effect of L-carnitine and soybean oil on performance and nitrogen and energy utilization by neonatal and young pigs. AB - A total of 64 neonatal pigs was used in an experiment to study the effect of L carnitine and soybean oil on pig performance and N and energy utilization. Pigs were weaned at an average of 3 d of age and individually fed diets that contained dextrose, corn syrup solids, and isolated soy protein for 21 d. Two levels of soybean oil (1.18 or 12.31%) and L-carnitine (0 or 800 ppm) were used in a factorial arrangement of treatments. Diets were formulated to contain the same nutrient content per megacalorie of ME. Total fecal and urine collections were made from d 17 to 21 of the experiment. Pigs were paired within treatments on d 21 and housed in pens until d 63. L-carnitine was lowered to 750 ppm and the soybean oil additions were 1.15 or 13.22% from d 21 to 42 and 2.17 or 14.74% from d 42 to 63. Soybean meal replaced isolated soy protein from d 42 to 63. Analysis of covariance was used with calculated ME intake per day as the covariate. There were no carnitine x soybean oil interactions (P > .05) for any criteria measured. L-carnitine or soybean oil did not (P > .05) affect ADG, grams of gain per megacalorie of ME, ME as a percentage of GE or N retained as a percentage of N consumed. In conclusion, L-carnitine did not improve the utilization of ME in diets that contained high additions of soybean oil, and calories from soybean oil were utilized as effectively as calories from carbohydrate by neonatal and young pigs. PMID- 8454538 TI - Effect of long-term addition of folic acid on folate status, growth performance, puberty attainment, and reproductive capacity of gilts. AB - Three groups of 34 gilts received, from 9 wk of age until slaughter at 7 wk of gestation, diets supplemented with either 0, 5, or 15 mg/kg of folic acid. The concentration of serum folates increased linearly (P < or = .05) with the level of added folic acid. Although the growth performance was not influenced by the treatments during the overall growing period, feed intake (P < or = .10) and body weight gain (P < or = .05) from 17 to 21 wk of age increased linearly as folic acid level in the diet increased. Age and body weight at puberty as well as body weight gain during gestation were not influenced (P > or = .32) by treatments. Dietary folic acid addition did not affect (P > or = .21) either total weight and empty weight of uterine horns or ovarian total weight, stroma weight, and number and weights of corpora lutea. No treatment effect (P > or = .35) was observed on placental surface, number of placental areolae, litter size, fetus weight, or total litter weight or on fetal DNA, RNA, and protein. However, the concentration of folates in fetuses increased linearly (P < or = .03) with the addition of folic acid in the dam's diet. In conclusion, although a dietary addition of as high as 15 mg/kg of folic acid seemed to influence growth performance of gilts by the end of the growing period, it did not affect age at puberty.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454541 TI - Performance of young pigs: relationships with periparturient progesterone, prolactin, and insulin of sows. AB - Blood collected from 54 sows over 2 to 8 d of the periparturient period was assayed for progesterone, insulin, and prolactin to determine whether the sows' hormonal state was correlated with perinatal pig mortality and weight gain. Sows with larger litters had higher concentrations of progesterone and prolactin and a lower concentration of preprandial insulin during the 48 h preceding parturition. Pig mortality was higher in larger litters and involved pigs of lower birth weight. Most pigs that died lost weight during the 24 to 48 h that preceded their deaths. Litters with lower weight gain during the first 24 h postpartum tended to have higher mortality during the next 48 h. For some sows, progesterone remained elevated during the 48 h postpartum and litters of these sows had lower than average 3-d weight gains. Low milk intake by pigs is a major cause of death and poor growth, and we suggest that poor milk production by the sow is one contributing factor. Elevated postpartum progesterone may inhibit lactogenesis and contribute to poor pig performance. PMID- 8454539 TI - The effects of endophyte-infected tall fescue consumption and use of a dopamine antagonist on intake, digestibility, body temperature, and blood constituents in sheep. AB - Two experiments were conducted with lambs that consumed endophyte-infected (Acremonium coenophialum) tall fescue diets under elevated temperature and humidity and supplemented with the dopamine antagonist metoclopramide (M). In Exp. 1, 12 ruminally cannulated wethers (average weight 49 kg) were allotted by weight to either an endophyte-free diet (E-) or endophyte-infected diet (E+; 1,170 ppb of ergovaline), or E+ supplemented with M (15 mg/kg of lamb BW; E+M). Ad libitum DM intake and digestibility were lower (P < .05) for E+ than for E- diet. Supplementation of E+ with M increased (P < .05) DM intake by 27.6% but did not change DM digestibility. Body temperature increased (P < .05) when lambs consumed E+ and was further increased when M was supplemented. For Exp. 2, 19 wether lambs (average weight 24 kg) were allotted to treatments to evaluate the effects of endophyte consumption (0 vs 2,430 ppb of ergovaline) and supplementation with M (0 vs 20 mg/kg BW). An interaction (P < .05) of main effects was measured for DM intake. Lambs that consumed E+M consumed more DM than did lambs fed only E+, but lambs offered the E- diet and supplemented with M did not increase DM consumption. Diet DM digestibility was not different among treatments. Skin vaporization decreased (P < .05) due to E+ consumption and M supplementation. The concentration of prolactin in plasma was decreased (P < .05) by consumption of E+ (8 vs 136 ng/mL) and did not increase due to M supplementation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454540 TI - The effects of endophyte-infected tall fescue consumption on diet utilization and thermal regulation in cattle. AB - Two experiments were conducted to determine the effects of endophyte fungus (Acremonium coenophialum) ingestion in tall fescue diets and environmental temperature on heat dissipation and diet utilization by cattle. In Exp. 1, 12 Angus heifers (average weight 244 kg) were allotted by weight to either an endophyte-free (E-) or endophyte-infected (E+; 381 ppb of ergovaline) diet. Environmental temperature varied between 22 and 32 degrees C. Voluntary DM and water intakes were similar (P > .10) among treatments. Rectal temperatures and concentrations of prolactin in plasma were lower (P < .05) after ingestion of the E+ diet. Plasma triiodothyronine, thyroxine, and cortisol concentrations were not affected by diet. In Exp. 2, 24 Holstein steers (average weight 114 kg) were allotted by weight to either E- or E+ (285 ppb of ergovaline) and one of two environmental temperatures (22 or 32 degrees C). At 32 degrees C, feed intake was reduced by 22%, and water consumption was increased by 62% compared with steers housed at 22 degrees C. Consumption of E+ reduced feed intake by 10% but did not influence water consumption. Plasma concentration of prolactin was decreased (P < .05) within 48 h after consumption of E+. Rectal temperatures increased in response to both environmental temperature (P < .05) and E+ consumption (P = .06). Digestibilities of DM and OM for E+ were 9% lower (P < .05) than for E .(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454542 TI - Administration of GnRH at estrus influences pregnancy rates, serum concentrations of LH, FSH, estradiol-17 beta, pregnancy-specific protein B, and progesterone, proportion of luteal cell types, and in vitro production of progesterone in dairy cows. AB - Four experiments were conducted to examine effects of GnRH administered at estrus on various reproductive characteristics in repeat-breeding dairy cows (eligible for third service). In Exp. 1, cows (n = 8 per group) received (i.m.) either saline or 50, 100, or 250 micrograms of GnRH at 12 h after onset of estrus. There was a positive linear (P < .05) effect of dose on concentrations of LH, but not of FSH, in serum at 2 h after the injection. Concentrations of progesterone (P4) were higher (P = .10) through 16 d after estrus in nonpregnant cows that returned to estrus 18 to 24 d after GnRH treatment than in nonpregnant cows given saline. Likewise, among cows with elevated concentrations of P4 through 30 d after estrus (diagnosed pregnant by increased concentrations of pregnancy-specific protein B; PSPB), P4 was higher (P = .10) in those given GnRH than in those given saline. In Exp. 2, concentrations of LH, FSH, and estradiol-17 beta (E2) were similar among 12 cows during the periestrual period before they received (i.m.) 100 micrograms of GnRH or saline at estrus. Concentrations of P4 after estrus were increased 2 d earlier (P < .05) in GnRH- than in saline-treated cows. Among cows with elevated concentrations of P4 and PSPB through 40 d after AI, P4 was higher (P < .05) in those given GnRH than in those given saline. In Exp. 1 and 2, a greater proportion (43 vs 14%; P = .07) of cows given GnRH was pregnant 42 to 56 d after estrus than of those given saline, but calving rate was similar (27 vs 14%). In Exp. 3, average number of LH pulses per 8 h was similar between saline- and GnRH treated cows on d 1, 3, and 8, but overall concentrations of LH were reduced (P < .05) in GnRH-treated cows. Concentrations and number of pulses of FSH were increased (P < .05) on d 8 after treatment with GnRH. Concentrations of P4 were increased earlier (P < .05) after estrus in GnRH-treated (69 +/- 12 h) than in saline-treated cows (126 +/- 12 h), with higher (P < .05) concentrations of P4 on d 4 to 8. In Exp. 4, eight cows received either 100 micrograms of GnRH or saline at 12 h after onset of estrus (d 0) in a cross-over design.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8454545 TI - The effects of feeding regimen and dietary sucrose supplementation on natural abundance of 15N in some components of ruminal fluid and plasma of sheep. AB - An experiment was conducted to investigate the effects of changes in ruminal conditions arising from feeding and sucrose supplementation to the diet on the natural abundance of 15N (delta 15N value) of some biological components and of feces and urine in sheep. Four wethers fitted with ruminal fistulas were fed on alfalfa hay cubes with or without sucrose either 2 or 12 times daily. With twice daily feeding, the delta 15N values of ruminal ammonia and plasma urea decreased after feeding, whereas only small changes were observed throughout the sampling period with 12 times daily feeding. With 12 times daily feeding with and without sucrose, the delta 15N values of ruminal ammonia were higher (P < .05) than those of the diet and plasma urea. The delta 15N values of ruminal bacteria were lower (P < .05) than those of ruminal ammonia but higher (P < .05) than those of the diet. The delta 15N values for feces were higher (P < .05) than those of the diet, and no differences (P > .25) were observed between the delta 15N values of urine and those of the diet. Dietary sucrose supplementation lowered (P < .05) the delta 15N values of ruminal ammonia but had no effect (P > .10) on values for ruminal bacteria and plasma urea. Nitrogen excretion in urine was decreased (P < .05) by sucrose supplementation to the diet, but the delta 15N value of urine showed no effect (P > .25) of sucrose addition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454543 TI - Effect of freezing semen and dosage of sperm on number of accessory sperm, fertility, and embryo quality in artificially inseminated cattle. AB - This experiment was conducted to determine whether use of fresh or frozen semen at either 20 x 10(6) (low) or 100 x 10(6) (high) sperm per dose affects the number of accessory sperm and fertilization status/embryo quality as determined from ova/embryos recovered nonsurgically 6 d after insemination. Ejaculates of four bulls were split and prepared for use as fresh or frozen semen at either the high or low dose. From 129 inseminations to normally cycling cows, 98 ova/embryos were recovered. To reduce male effects, ova/embryos used were randomly balanced across treatments, by ejaculate within bull for evaluation of frozen vs fresh semen (n = 80) and by bull for evaluation of high vs low dosage treatments (n = 76). Distribution of accessory sperm was highly skewed downward; thus, median values were more meaningful than means. Freezing semen had no significant effect on fertility status/embryo quality or number of accessory sperm at either dosage. Increasing dosage improved the number of accessory sperm per ovum or embryo (median value) and fertility status/embryo quality (P < .05). Mean +/- SD and median values for accessory sperm were 37.8 +/- 38.3 and 27.5; 28.9 +/- 62.8 and 3.0 for the high and low dose, respectively. Percentage of unfertilized ova, degenerate embryos, and embryos classified poor to fair and good to excellent were 3, 5, 24, 68, and 21, 16, 18, 45, for the high and low dose, respectively. We conclude that number of accessory sperm and fertility status/embryo quality respond favorably to increased dosage of semen and that freezing semen in this study was not detrimental to these parameters. PMID- 8454544 TI - Influence of addition of monensin to an alfalfa hay diet on net portal and hepatic nutrient flux in steers. AB - Six Holstein steers (381 +/- 11 kg BW; mean +/- SE) surgically fitted with hepatic portal (n = 6), hepatic venous (n = 4), mesenteric venous, and arterial catheters were used in a replicated crossover design experiment to evaluate the influence of monensin addition to an alfalfa hay diet on net portal and hepatic nutrient flux. Steers were fed 6.5 kg of DM/d in 12 portions using automatic feeders. Diets included chopped alfalfa hay (20.4% CP) plus 418 g of DM/d of finely ground corn (8.5% CP) with monensin added (240 mg/d) for treated steers. Experimental periods lasted 21 d, with blood samples taken on the final 2 d of each period. Five sets of arterial, portal, and hepatic blood samples were collected hourly from 0900 to 1300 each day. Ruminal fluid samples were collected by stomach tube at the end of each sampling day for VFA analysis. Blood flow was determined by a primed-continuous infusion of p-aminohippurate into the mesenteric venous catheter. Addition of monensin increased (P = .04) the molar percentage of ruminal propionate and decreased ruminal isobutyrate (P = .02) and isovalerate (P = .03). Percentages of the other ruminal VFA, total ruminal VFA concentration, and pH were not affected by feeding monensin. The arterial concentrations of L-lactate (P = .02) and beta-hydroxybutyrate (P = .01) were greater with monensin; however, none of the arterial concentrations of the other metabolites was changed. Feeding of monensin also did not affect (P > .10) portal, hepatic, or hepatic arterial blood flow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454546 TI - Effect of level of supplemental chromium on performance, serum constituents, and immune status of stressed feeder calves. AB - The effects of level of supplemental Cr from high-Cr yeast on performance, blood chemistry profile, morbidity, and immune status were investigated using 84 Charolais-crossed steer calves in a completely randomized design. Calves of 236 kg average weight, after transportation from Saskatchewan to Ontario, were randomly assigned to four treatments; 0, .2, .5, and 1 ppm of supplemental Cr, incorporated into a corn-silage diet. Blood was collected via jugular venipuncture at d 0, 7, 14, 21, and 28 and analyzed for metabolites, minerals, immunoglobulins, hematocrit (Hct), and leucocyte counts. Hemagglutinating antibody titers to human red blood cells (HRBC) were quantified after immunizations on d 0 and 14. Contact sensitivity after sensitization and challenge with dinitrochlorobenzene was also measured. A 27% increase (P < .05) in ADG was observed at d 30 for calves that were fed .2 and 1 ppm of supplemental Cr. Dry matter intake also increased (P < .05) for the .2- and 1-ppm Cr treatments. A linear decrease (P < .05) in serum cortisol with increasing Cr level was observed at d 28. Chromium supplementation decreased (P < .05) morbidity, as well as rectal temperatures at d 2 and 5. Peak primary antibody titers to HRBC (P < .05) and immunoglobulin G1 concentrations (P = .06) at d 14 were higher for steers that received the Cr supplementation. However, Cr treatment had no effect on expression of contact sensitivity. Chromium supplementation increased (P < .05) Hct on d 14 and 21 and serum Ca and Mg on d 7.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454547 TI - Supplemental folic acid: a requirement for optimizing swine reproduction. AB - The administration of supplemental folic acid to female reproducing swine (either via injection or dietary supplementation) is a fairly recent research phenomenon. The majority of publications have occurred during the past 5 yr; few publications on this topic appeared before 1983. Although folic acid supplementation is a young research area compared to that involving many other vitamins, the reported results are quite consistent. There seem to be no major benefits to lactational supplementation; although supplementation in lactation is effective in elevating sow serum folate, milk folate, and nursing pig serum folate, it has not produced changes in sow BW, litter size weaned, or pig gain. Supplementation during gestation has yielded a consistent benefit: a positive response in total pigs born in all studies. The response in gestation of increased litter size seems to be a result of improved embryo or fetal survival rather than increased ovulation, although the mechanism whereby survival rate is improved is yet to be understood. Clearly, supplemental folic acid is required to maximize sow prolificacy. PMID- 8454549 TI - Influence of processing on the comparative feeding value of barley for feedlot cattle. AB - Ninety-six crossbred steers were used in a 172-d feedlot growth performance trial to determine the effects of type processing on the comparative feeding value of barley in a 90% concentrate finishing diet. Treatments were: 1) steam-flaked corn (SFC; density = .31 kg/L); 2) dry-rolled barley (DRB; density = .39 kg/L); 3) steam-rolled barley, coarse roll (SRB-C, density = .39 kg/L); and 4) SRB, thin roll (SRB-T, density = .19 kg/L). The ADG was similar (P > .10) across barley treatments, averaging 1.29 kg/d. Feed intake (P < .05) was lower for SRB than for DRB. Diet NE was greater (P < .05) for SRB than for DRB. Feed intake was lower (P < .05) for SFC than for barley diets. The influence of grain processing on characteristics of digestion was evaluated using four Holstein steers (average BW = 230 kg) with cannulas in the rumen and proximal duodenum. Ruminal and total tract digestibility of OM and starch were lower (P < .05) for DRB than for SRB. Ruminal and total tract digestibility of OM and starch were similar (P > .10) for SRB-C and SRB-T. However, passage of nonammonia N was markedly increased (26.9%, P < .01) with SRB-T compared with SRB-C. This increase in ruminal N efficiency was due partly to reduced ruminal degradation of feed N (23.4%, P < .01) and partly to increased microbial N synthesis (13.3%, P > .10). The comparative feeding value of DRB, SRB-C, and SRB-T in this study was 90, 92, and 96% the value of SFC, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454548 TI - Effects of supplemental beta-carotene and vitamin A on reproduction in swine. AB - Since its discovery some 80 yr ago, many advances have been made in understanding the many diverse roles of vitamin A (retinoids). Among these are the critical roles that vitamin A plays in regulating reproduction in both the male and female. The identification of retinol-binding proteins produced by the pig uterus and conceptus marks an exciting event. It will be pivotal to future efforts in elucidating the mechanism by which retinoids regulate conceptus development and steroidogenesis. However, relatively little is known of the possible direct role played by its provitamin, beta-carotene, in controlling reproduction in the pig. However, future research likely will address this aspect of carotenoid function. PMID- 8454550 TI - Substitution of peanut skins for soybean hulls in steer finishing diets containing recommended and elevated crude protein levels. AB - A steer finishing trial was conducted to study the substitution of peanut skins (PS) for soybean hulls (SH) when included at three levels (0, 7.5, or 15%) in diets containing recommended (10.5% = RP) or elevated (15.5% = HP) levels of CP. Average daily gain, DMI, and gain:feed ratios decreased linearly (P < .01) when steers were fed RP and increasing levels of PS. Average daily gain and DMI increased linearly (P < .05) when steers were fed HP and increasing levels of PS. Carcass quality grades were greater (P < .05) for steers fed the HP-15% PS diet than for steers fed either the RP-15% SH or HP-15% SH diets. Ruminal fluid ammonia concentrations were greater (P < .05) for HP diets and decreased linearly (P < .05) with increasing levels of PS at both RP and HP. Nutrient fractions of the HP diets were more (P < .05) digestible for CF, NDF, and ADF than for the RP diets. In general, the HP-7.5% SH/PS diet was more digestible than the other diets in the comparison. When SH are fed as 15% of the diet, PS can be substituted for SH up to 7.5% of the diet at RP levels and can be used to completely replace SH at HP levels. PMID- 8454551 TI - Economical and biological efficiencies of beef cattle differing in level of milk production. AB - Economical and biological efficiencies of beef production to weaning and to slaughter were estimated in three groups, different in milk available (low, medium, and high) to the calves but with the same potential for growth. Data from different breed groups of cows (low [L] = Hereford x Angus, medium [M] = Red Poll x Angus, and high [H] = Milking Shorthorn x Angus) were used. Economical efficiency was the ratio of income to expenses and biological efficiency was the ratio of calf weight to total feed energy required. Income was derived from cull cows and calves at weaning or carcasses of calves fed to slaughter. Feed and non feed expenses for the cowherd and for calves to weaning or to slaughter were included in economical efficiency. Efficiencies were estimated assuming observed reproductive rates and energy requirements for maintenance, as well as for equal reproductive rates and equal energy requirements for maintenance in the M and H groups. With the observed reproductive rates and maintenance requirements, biological efficiencies to weaning and to slaughter were 28.1, 27.2, and 27.5 g of weaning weight and 22.0, 20.4, and 20.3 g of carcass weight per megacalorie of ME for L, M, and H, respectively; the corresponding values using equal reproduction and equal maintenance in M and H were 28.3, 27.2, and 27.4 g of weaning weight and 22.1, 20.5, and 20.5 g of carcass weight per megacalorie of ME.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454552 TI - Technical note: computing tests of fixed effects in a restricted class of mixed models. AB - Inferences about fixed effects in mixed linear models are important in a variety of animal science studies. The statistical theory for making such inferences is well known, and if the variance components are known up to a proportionality constant, then optimal exact tests can be performed. Computing the test statistics, however, can still be problematic when the random effects have many levels. In practice, approximate tests that are easily computed but less efficient are usually employed. This article describes reduction in error sum of squares procedures for performing the exact test and for computing associated confidence intervals. By taking advantage of iterative algorithms for solving Henderson's mixed-model equations, the tests can be performed without inverting the covariance matrix or computing a generalized inverse of the mixed-model coefficient matrix. The procedures are illustrated on an animal model that has three random effects, two with 1,372 levels and one with 450 levels. PMID- 8454553 TI - Animal model estimation of additive and dominance variances in egg production traits of poultry. AB - An animal model analysis was used to estimate simultaneously additive (sigma 2a) and dominance (sigma 2d) variances for egg production traits within three White Leghorn lines. The data consisted of information for three generations on egg number (EN) produced at 18 to 25 (EN1), 26 to 65 (EN2), and 18 to 65 wk of age (EN3); egg weight (EW) measured at 30 to 35 (EW1) and 40 to 45 wk (EW2); and egg specific gravity (ESG) measured at 30 to 35 (ESG1) and 40 to 45 wk (ESG2). A transformation was used for EN2 and EN3 because of a skewed distribution. In total, 813 sires, 2,575 dams, and 28,649 daughters were involved in the analyses. Three genetic models (sire-dam, additive, and dominance) were compared in estimating heritability (h2). The sire-dam model underestimated h2 because it ignored animal relationships. The h2 estimates from the additive model were approximately 9 to 52% higher for EN and 2 to 18% higher for EW and ESG than those from the dominance model. The differences between the h2 estimates from the additive and dominance models were increased for larger dominance variance sigma 2d. Ratios of sigma 2d to total variance were high for EN (10 to 20%) and low for EW and ESG (1 to 13%). Ratios of sigma 2d to total genetic variance for EN1, EN2, EN3, EW1, EW2, ESG1, and ESG2 were 18 to 36, 29 to 43, 29 to 56, 1 to 26, 3 to 8, 20 to 27, and 2 to 14%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454556 TI - Body and carcass composition of Angus and Charolais steers as affected by age and nutrition. AB - The objectives of this study were to examine the effects of a low vs moderate rate of gain during the growing phase on empty body and carcass composition during finishing of Angus and Charolais steers of two ages. Forty-eight Angus and 48 Charolais steers that were either spring-born (OLDER) or fall-born (YOUNGER) were fed two diets (alfalfa pellets [CON] or cubed grass-alfalfa hay, wheat straw, cottonseed hulls, and soybean meal [RES]) for a growing period followed by a conventional feedlot period. The feedlot period started when the YOUNGER-CON steers weighed the same as the OLDER-RES steers. At that time, an interaction of age x diet occurred in empty body fat content (P < .10), whereas breed and age x diet affected carcass fat content (P < .01). OLDER-CON steers were larger (average 378 kg empty BW) and fatter than the other, smaller groups (average 222 kg). Angus carcasses were fatter than Charolais carcasses (P < .01). At the end of the finishing phase, compensating steers (OLDER-RES) had fatter carcasses than OLDER-CON steers. Empty body fat content was affected by a breed x age x diet interaction (P < .10). Allometric regressions (Y = aXb) of fat on empty BW indicated that empty body fat accretion was greater in Angus than in Charolais and in YOUNGER than in OLDER steers. A breed x age x diet interaction (P < .10) indicated that OLDER-Angus had higher fat accretive rates than YOUNGER-Angus, whereas OLDER-CON-Charolais steers deposited fat more slowly than the remaining groups. These data suggest that steers receiving feedlot diets at light weights, whether young in age or previously restricted, accumulate fat more rapidly than do larger steers. This feeding strategy may be an advantage in late-maturing types, but moderate growth through approximately 75% of slaughter weight is recommended for early-maturing types. PMID- 8454554 TI - Effect of genetic groups on estimates of additive genetic variance. AB - This study examined the effect of genetic grouping on REML estimates of additive genetic variance with an animal model with selected base populations. A simulated population of 40 animals (20 males and 20 females) was followed under selection or random mating conditions for 10 generations. Each population was replicated 20 or 50 times. Genetic grouping reduced estimates of additive genetic variance in populations with selected base animals, whereas grouping had little effect on the estimate in unselected populations. The effect of genetic grouping varied according to the quantity and kind of information that was missing (percentage of deleted data and pattern of deletion). When genetic grouping was completely random, the estimates were unaffected. Because including genetic groups in the model for analysis affected the estimates of additive genetic variance, the question should be considered of what value or values for heritability should be used for genetic evaluation when grouping is used to account for prior selection. PMID- 8454557 TI - Effect of pH and ionic strength on bovine m-calpain and calpastatin activity. AB - The effects of bovine skeletal muscle m-calpain and calpastatin on the degradation of casein and isolated bovine myofibrils were characterized under various pH values (7.0, 6.2, 5.7) and ionic strengths (32 to 400 mM KCl) at 25 degrees C. Caseinolytic assays indicated that m-calpain activity increased with increasing pH (P < .01) but decreased with increasing ionic strength (P < .01). Regardless of the presence of m-calpain, SDS-PAGE of myofibrils showed increased solubilization of myofibrillar proteins as pH and ionic strength increased. However, only in the presence of m-calpain were changes normally observed during postmortem storage reproduced. Protein release attributed to m-calpain activity increased with pH, but the effects of elevated ionic strength on the ability of m calpain to hydrolyze myofibrillar proteins were not evident from SDS-PAGE, except for the decreased troponin-T degradation by m-calpain at the higher ionic strengths. A pH x ionic strength interaction was observed for calpastatin activity determined by caseinolytic assays (P < .01). No changes in m-calpain inhibition were detected at pH 7.0 and 6.2 at different ionic strengths. However, at pH 5.7 the ability of calpastatin to inhibit m-calpain decreased with increasing ionic strength. No changes in m-calpain inhibition could be detected with SDS-PAGE. Based on these results, it can be concluded that although m calpain and calpastatin activities decrease with increasing ionic strength, their activities in the presence of myofibrils were not affected by ionic strengths typically found in postmortem muscle. PMID- 8454558 TI - Human polymorphonuclear leukocytes have dual effects on endothelin-1: the induction of endothelin-1 mRNA expression in vascular endothelial cells and modification of the endothelin-1 molecule. AB - The effect of human polymorphonuclear leukocytes (PMNs) on the expression of the endothelin-1 (ET-1) gene and the production of ET-1 peptide was investigated. Human PMNs were separated from venous blood with Mono-Poly Resolving Medium and activated by incubation with formyl-methionyl-lencylphenylalanine (FMLP) (1 microM). Then PMN suspension was added to cultured porcine endothelial cell monolayers and coincubated for various periods. Following the coincubation, ET-1 mRNA in endothelial cells was examined by Northern blotting and immunoreactive ET 1 (irET-1) peptide levels in the conditioned media were measured by an enzyme linked immunosorbent assay (ELISA). Similar experiments were also carried out with cell-free PMN supernatant. Untreated and activated PMNs led to a 1.4-fold and 6.3-fold increase in ET-1 mRNA levels in endothelial cells, respectively, at 6h, while irET-1 peptide levels did not significantly increase as compared with control. In contrast, when PMNs were coincubated in the presence of an Intercell chamber without direct contact to endothelial cells, PMNs did not induce ET-1 mRNA expression in endothelial cells, and significantly decreased irET-1 peptide levels in the conditioned media. Cell-free PMN supernatant did not have all these effects on ET-1. These findings suggest that direct PMN-endothelial cell contact was essential for PMN-induced expression of the ET-1 gene and that PMNs may decrease irET-1 through some modification of the ET-1 molecule. PMID- 8454555 TI - A semiautomatic device for feeding liquid milk-replacer diets to infant pigs. AB - We describe the design and use of a device that enables the semiautomatic feeding of various quantities of liquid, milk-replacer diet. The apparatus consists of a programmable fraction collector (with attachments for preparative work) driven by a high-flow peristaltic pump. To reduce bacterial growth and lipid oxidation of the liquid diet, we kept the milk-replacer in an ice bath and bubbled a slow stream of nitrogen through it at all times. The liquid diet was kept in suspension by continuous recirculation and agitation. The device can be used to dispense prespecified amounts of either the same volume of feed, or a different volume to each of two groups of animals at regular intervals over 24 h; alternatively, by using the time-windows feature of the fraction collector, up to 11 different volumes can be dispensed to 11 animals. We present results of a preliminary trial in which we used the equipment to feed 11 pigs, weaned at 1 d of age, for 11 d. Daily maintenance and programming of two systems, including diet preparation and pig weight measurements, were accomplished in approximately 90 min. The feeder is simple to program and enables the feed intake of the pigs to be adjusted accurately for individual BW on a daily basis. The pigs had no diarrhea and grew well on the rations allocated to them. PMID- 8454559 TI - Lacidipine, a new long-acting dihydropyridine calcium antagonist, has high vascular selectivity against all intracardiac variables. AB - Vascular selectivity of lacidipine, a new potent and long-acting coronary vasodilator, was evaluated by a comparison with its negative inotropic, chronotropic, and dromotropic effects in canine isolated, blood-perfused heart preparations. The drug was injected into each nutrient artery in a bolus fashion. In the papillary muscle preparation, the dose causing a 50% increase in blood flow through the anterior septal artery was 0.23 micrograms (mean of five experiments) and the time required for return to half maximum at this dose was 15.0 min even with a bolus injection. Meanwhile, the dose causing a 50% decrease in developed tension of the papillary muscle was 4.6 micrograms. The dose producing a 15% decrease in sinoatrial rate in the sinoatrial node preparation was 8.4 micrograms (n = 5) and that causing a 50% increase in atrio-His interval in the atrioventricular node preparation was 6.8 micrograms (n = 7). These results indicate that the vascular selectivity of lacidipine is markedly high not only against ventricular contractility but also against sinoatrial node automaticity and atrioventricular nodal conduction. The high lipophilicity of lacidipine might be related, at least in part, to its high vascular selectivity, which was equieffective against all the intracardiac variables measured. PMID- 8454560 TI - Left ventricular filling measured by Doppler echocardiography during dynamic exercise in patients with myocardial infarction. AB - To assess left ventricular diastolic properties in response to dynamic exercise, mitral inflow velocity integrals were measured by pulsed-wave Doppler echocardiography in ten patients with myocardial infarction and in ten normal subjects, and simultaneous left ventricular pressure was obtained with micromanometry in the patients. Early filling velocity integrals were maintained in the patients during exercise. Late filling velocity integrals were not augmented during exercise in the patients, but were increased in the normal subjects. In the patients, there was an increase in mitral valve opening pressure, left ventricular end-diastolic pressure, and the time constant of left ventricular isovolumic pressure decay. The lowest diastolic pressure and the number of time constants that had elapsed before the lowest diastolic pressure remained unchanged. These results show that in patients with myocardial infarction, early filling is maintained by an increase in driving pressure during exercise, despite incomplete relaxation. Augmentation of late filling, seen in normal subjects, is impaired in patients with myocardial infarction, probably due to an increase in left ventricular stiffness. PMID- 8454561 TI - Long-term performance of beta-propiolactone-treated nonviable homograft for aortic valve replacement and right ventricular outflow tract reconstruction. AB - The long-term performance of beta-propiolactone-treated homografts was clearly different between operative survivors of aortic valve replacement (n = 27) and those of right ventricular outflow tract reconstruction (n = 11). The reoperation free survival rate at 20 years was 14.8 +/- 6.8 (standard error)% in the former and 77.8 +/- 13.9% in the latter. Even a nonviable aortic homograft can be favorably accepted as a material for right ventricular outflow tract reconstruction in contrast to the aortic position. PMID- 8454565 TI - Comparative study of various genetic hypertensive rat strains: blood pressure, body weight, growth and organ weights. AB - In an attempt to compare various genetic strains of hypertensive rats, representative hypertensive strains and associated controls (male, 1-month-old, 6 10 of each strain and 18 strains in total) were collected at a single center (National Institutes of Health; NIH, United States), maintained under the same experimental conditions with normal sodium NIH open formula diet and studied by a single investigator using standard techniques. Animals were measured for blood pressure (BP) by a tail-cuff method without anesthesia and body weight (BW) at 10 and 12 weeks of age and killed to measure organ weights. Hypertension was severe (> 190 mmHg) in spontaneously hypertensive rats (SHR) and their stroke-prone substrains at 12 weeks of age but mild to moderate (145-160 mmHg) in the rest of the hypertensive strains (Dahl's, Milan, Lyon, Sabra, and New Zealand Strains). Regarding organ size, partial correlation analysis showed that organ weights, except for brain and adrenal glands, are good functions of BW and that weight of the left ventricle (LV) was the only one significantly linked to BP levels. A bivariate regression model for LV weight was obtained as follows: LV(mg) = 1.478 BW(g) + 2.13BP(mmHg) - 51(R = 0.878, P < 0.001). The presence of some genetic factor regulating relative organ size independently of BW and BP was suggested in LV weight as well as in the weight of the other organs. Among the strains, MHS was found to be unique for the smallest kidney size and New Zealand strains for the greatest relative LV size when adjusted to allow for the influence of BP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454563 TI - Successful repair and postoperative management of tetralogy of Fallot in a patient with maple syrup urine disease. AB - A case of tetralogy of Fallot with maple syrup urine disease (MSUD) treated surgically is reported. This 2-year-old female patient developed neurologic deterioration after intracardiac repair. Postoperative management, which included peritoneal dialysis, intravenous hyperalimentation, and early intestinal alimentation with branched-chain amino acid-free milk was successful. At the present time, two years after the operation, she is doing quite well with a special diet for MSUD. This is the first report on a patient with MSUD who underwent open heart surgery using a cardiopulmonary bypass, stressing the importance of postoperative management. PMID- 8454564 TI - Anomalous origin of the left coronary artery from the right pulmonary artery: report of a case. AB - A 1-year-old boy was referred to our hospital for further investigation of mitral regurgitation. Color-Doppler echocardiography revealed the site of the anomalous origin of the left coronary artery which was confirmed by a cineangiographic study. This case is interesting for several reasons: the first is that the anomalous left coronary artery originated from the right pulmonary artery; the second is that two-dimensional echocardiographic findings can be misleading, i.e., a vessel-like structure which seemed to be the left coronary artery arising normally from the aorta was visualized; and the last is that a two-dimensional color-Doppler echocardiogram was useful in the diagnosis of the anomalous origin of the left coronary artery. The patient underwent implantation of the anomalous left coronary artery as well as Kay's plasty of the mitral valve, and has been doing well since then. PMID- 8454562 TI - Prognostic significance of electrocardiographic findings in patients with dilated cardiomyopathy. AB - The prognostic significance of electrocardiographic variables was retrospectively investigated in 88 patients with dilated cardiomyopathy and with normal coronary arteriograms. During an average follow-up of 3.7 +/- 2.9 years, 43 patients died, 26 of progressive heart failure, 15 patients with sudden death, and one due to cerebral embolism. Excluding one patient, who died of esophageal cancer, the cumulative survival rate was 73% at 2 years and 60% at 5 years. By univariate life table analysis, abnormal Q-waves, a QRS duration > or = 0.12s, a cardiothoracic ratio > or = 60%, systolic blood pressure < 110mmHg, and left ventricular end-diastolic pressure > or = 15mmHg were significantly associated with increased mortality within 5 years. Multivariate analysis using Cox's proportional hazards model determined the major independent risk factors in the following order: (1) for all patients; the presence of abnormal Q-waves, left bundle branch block or intraventricular conduction disturbances, left ventricular end-diastolic pressure, systolic blood pressure and the cardiothoracic ratio; (2) for patients without left bundle branch block or intraventricular conduction disturbances; abnormal Q-waves, left ventricular end-diastolic pressure and systolic blood pressure. The present study thus demonstrated that the electrocardiogram could provide independent prognostic predictors in patients with dilated cardiomyopathy, possibly reflecting the severity of myocardial damage. PMID- 8454566 TI - Zinc protease of Bacillus subtilis var. amylosacchariticus: construction of a three-dimensional model and comparison with thermolysin. AB - The active site structure of the Zn-containing neutral protease from Bacillus subtilis var. amylosacchariticus (BANP) was predicted by computer-aided modeling on the basis of the three-dimensional structure of thermolysin (TLN). As expected from the high homology in amino acid sequence of the two enzymes, the overall folding of BANP was very similar to that of TLN. Glu144, Tyr158, and His228 of BANP were located near the active site Zn ion, to which three amino acid residues, His143, His147, and Glu167, were coordinated. This model is supported by the previous results that chemical modifications of Tyr158 and photooxidation of His228 of BANP markedly affect the proteolytic activity of the enzyme. Interestingly, BANP was found to be significantly less sensitive to metalloprotease inhibitors such as phosphoramidon and talopeptin. From a comparison of the enzyme-inhibitor complex models between BANP and thermolysin, it is suggested that replacement of Thr129 in TLN by Phe130 in BANP is related to difference in inhibitor sensitivity between BANP and TLN. PMID- 8454567 TI - 13C- and 15N-NMR studies on medium-chain acyl-CoA dehydrogenase reconstituted with 13C- and 15N-enriched flavin adenine dinucleotide. AB - The 13C- and 15N-NMR spectra of porcine kidney medium-chain acyl-CoA dehydrogenase (MCAD) reconstituted with 13C- and 15N-enriched FADs were measured. The positions of selective enrichment were C(2), C(4), C(4 alpha), C(10 alpha), N(1), N(3), and N(5) of the isoalloxazine nucleus of FAD. The NMR signals of the labeled atoms were observed as broad but distinct peaks in each NMR spectrum. The chemical shift values of the 2-, 4-, 4 alpha-, and 10 alpha-13C for the oxidized form of MCAD were 159.5, 166.8, 141.1, and 155.5 ppm, respectively, relative to the methyl resonance of 3-(trimethylsilyl)propionic acid-d4, while those of 1-, 3 , and 5-15N for the oxidized form were 183.6, 161.1, and 334.7 ppm, relative to liquid ammonia, respectively. The upfield shift of 2-13C of MCAD relative to that of FMN in the aqueous medium and its downfield shift relative to that of tetraacetylriboflavin in an apolar medium imply that a weaker hydrogen bond exists between C(2) = O and apoMCAD or a water molecule than that of free FMN with a water molecule. That the 4-13C resonance was observed downfield-shifted relative to that of free FMN in aqueous solution suggests a strong hydrogen bond between C(4) = O and apoMCAD. The chemical shift for 4 alpha-13C in oxidized MCAD is considerably downfield-shifted from that of FMN or any other flavoprotein observed thus far, indicating a unique environment around this position in MCAD. The 1-15N resonance of MCAD was most upfield-shifted among the flavoproteins observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454570 TI - Engineering of artificial cell-adhesive proteins by grafting EILDVPST sequence derived from fibronectin. AB - Fibronectin contains at least two distinct oligopeptide sequences serving as signals for the interaction with cell surface adhesion receptors termed integrins. One of these sequences, Arg-Gly-Asp-Ser (RGDS) tetrapeptide, was shown to be transferred to a truncated form of Staphylococcal IgG-binding protein (hereafter referred to as tSPA) with retention of its cell-adhesive activity [Maeda, T. et al. (1989) J. Biol. Chem. 264, 15165-15168]. We have extended the observation to another cell-adhesive sequence, Glu-Ile-Leu-Asp-Val-Pro-Ser-Thr (referred to as "CS1" sequence), to demonstrate that: i) the tSPA grafted with the sequence mediated adhesion of human lymphoma and rhabdomyosarcoma cells, mouse melanoma cells, but not of hamster fibroblasts; ii) antibodies against integrin alpha 4 and beta 1 subunits specifically inhibited cell adhesion mediated by the CS1-grafted tSPA; iii) a heterodivalent tSPA grafted with both RGDS and CS1 sequences at different sites was more potent in promoting cell adhesion than the monovalent tSPAs grafted with either sequence alone. These results indicate that not only the RGDS but also the CS1 sequence can be transferred to tSPA with retention of its cell-adhesive activity as well as its cell-type specificity, and that the grafted CS1 sequence is recognized by the same integrin isotype as the authentic sequence within intact fibronectin. PMID- 8454568 TI - Hydrolysis of micellar diheptanoylphosphatidylcholine catalyzed by bovine pancreatic phospholipase A2: kinetic characterization of group I and II enzymes. AB - Initial velocity data for the hydrolysis of micellar 1,2-diheptanoyl-sn-glycero-3 phosphorylcholine (diC7PC) catalyzed by bovine pancreatic PLA2 (Group I) were analyzed using the Michaelis-Menten equation. The Km value for the micellar substrate was found to be independent of Ca2+ concentration, as was the Km value for the monodispersed substrate. The pH dependence curve of Km in the presence of saturating amounts of Ca2+ showed two transitions reflecting large pK shifts of two ionizable groups from 5.0 to 5.45 and from 9.5 to 10.25, whereas the Km value for the monodispersed substrate was independent of pH [Fujii et al. (1991) J. Biochem. 110, 1008-1015]. The pH dependence curve of kcat showed three transitions, indicating the participation of three ionizable groups with pK values of 5.45, 8.4, and 10.25. Deprotonation of the first group and protonation of the third group were found to be essential for catalysis. The respective groups were assigned as the catalytic group His 48, the N-terminal alpha-amino group, and invariant Tyr 52. The present results as well as those for another Group I PLA2 (Naja naja atra) are very different from those for Group II PLA2s (Agkistrodon halys blomhoffii and Trimeresurus flavoviridis), which showed Ca(2+) dependent substrate binding and no participation of the alpha-amino group in catalysis [Teshima et al. (1989) J. Biochem. 106, 518-527; Nishimura et al. (1992) J. Biochem. 111, 210-218].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454571 TI - Transcription of mouse ribosomal RNA gene with inactive extracts is activated by NAD+ in vitro. AB - S100 extract prepared from rapidly growing mouse FM3A cells (approx. 5 x 10(5) cells/ml) transcribed ribosomal RNA gene (rDNA) much more actively in vitro than that from stationary phase cells (1-2 x 10(6) cells/ml). When the inactive S100 extract was preincubated with NAD+, rDNA transcriptional activity was restored almost to the level of the active extract. The extract activated with NAD+ exhibited a gel-shift band in the gel mobility shift assay and enhancement of protection of the sequence between -44 and -8 nt from the initiation site from exonuclease III digestion. Such an extract labeled with [32P]NAD+ was analyzed by immunoprecipitation with anti-RNA polymerase I (pol I) antibody; a protein with M(r) 130 kDa was detected. In contrast, the polypeptide was hardly labeled in the active extract. 3-Aminobenzamide, a specific inhibitor of poly ADP-ribosylation, did not inhibit the activation by NAD+. These results suggest that the activation by NAD+ is due to enhancement of the formation of initiation complex by mono ADP ribosylation of the second-largest subunit (130 kDa) of pol I. PMID- 8454569 TI - A dynamical model for ribozyme function based on the sequential folding of pre mRNA transcripts. AB - Making use of parallel Monte Carlo simulations of competing folding pathways, we determine the specific stages in the in vivo sequential folding of group I pre mRNA transcripts where participation of a trans-acting factor or an already assembled portion of the transcript itself is required to generate a catalytically competent structure and subsequently shape the 3' splicing site. Thus, the model for ribozyme function revealed by the simulations should be regarded as dynamical since it is based on sequential folding. Our main aim is to prove that sequential folding warrants the chronology of splicing events required for ribozyme function, a feature which cannot be reproduced in existing static models of folding based on free energy minimization. The effect of trans-acting factors on the catalytically relevant folding pathway is assessed by comparing the in vitro folding pathway with the pathway that leads to the structure that splices the 5' extremity. The latter has been inferred previously by other authors using phylogenetic analysis. Since our model is rooted in multiprocessed folding algorithms, we concentrate on mitochondrial pre-mRNA transcripts belonging to group I which undergo no detectable self-splicing in vitro. As an illustrative example, the results have been specialized to the fourth intron of the yeast apocytochrome b gene (YCOB4). A crucial feature of our approach, irreproducible in previous models, is that it accounts for a meaningful scenario of competition between hydrolysis at the 3' extremity of the intron and exon-exon ligation. We prove that this scenario explains how the premature formation of conserved helix P10 is prevented until 5' cleavage has taken place.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454572 TI - Evidence for an increase in the association of cytosolic phospholipase A2 with the cytoskeleton of stimulated rabbit platelets. AB - Following stimulation of rabbit platelets with thrombin, phospholipase A2 (PLA2) activity increased in the Triton X-100-insoluble residue. Although the PLA2 activity was dependent on the protein content of the residue from the stimulated cells, the specific activity was higher than that in the case of unstimulated cells. The enzyme activity was inhibited by p-bromophenacyl bromide and increased significantly with 0.5-10 microM Ca2+. The enzyme hydrolyzed phospholipids having an arachidonoyl residue more effectively than ones with a linoleoyl residue. In addition, 70% of the enzyme activity was immunoprecipitated with a monoclonal antibody against cytosolic PLA2 of rabbit platelets, while it was inhibited by only 20% by an antibody that neutralizes the activity of group II PLA2. These results suggest an increase in the association of cytosolic PLA2 with cytoskeleton upon stimulation of rabbit platelets. PMID- 8454573 TI - Filament-forming domain of carp dorsal myosin rod. AB - Substructure of the myosin rod and its correlation to the filament formation were investigated by using fish myosin rod. It was found that fish rod contains a unique chymotrypsin susceptible site, 40 kDa from the COOH-terminus or 20 kDa downstream from the subfragment-2/light meromyosin junction (S-2/LMM junction). Cleavage at this new site produced subfragment-2 possessing 95 kDa subunit (95k S 2) and light meromyosin possessing 40 kDa subunit (40k LMM). The latter is the shortest unit ever reported to exhibit filament formation. Moreover, the 40k LMM was able to form filaments independently of the presence of Mg2+, while filament formation of rod and ordinary LMM (70k LMM) was promoted by Mg2+ addition. These results indicated that the Mg2+ binding sites are present within the NH2-terminal 20 kDa region of the 70k LMM. We concluded that the COOH-terminal 40 kDa portion of rod is responsible for the self-assembly ability of myosin, while the NH2 terminal 20 kDa region of the 70k LMM is the regulatory domain for thick filament formation through Mg(2+)-binding. PMID- 8454574 TI - Halobacterium halobium cytochrome b-558 and cytochrome b-562: purification and some properties. AB - Four different membrane-bound b-type cytochromes were found to occur in Halobacterium halobium strain L-33, and two of them, b-558 and b-562, were purified to homogeneity. Cytochrome b-558 showed absorption peaks at 414 and 526 nm in the oxidized form, and peaks at 425, 528, and 558 nm in the reduced form. Its alpha peak at 558 nm in the reduced form was asymmetric with a shoulder at around 554 nm. At liquid nitrogen temperature, the a the alpha peak was split into two peaks at 549 and 556 nm which appeared to be the alpha peaks of cytochromes c and b, respectively. The cytochrome contained 1 mol of protoheme in 28,500 g, and was composed of one molecule each of two subunits with molecular masses of 15.4 and 11.7 kDa, respectively. The heme seemed bound to the larger subunit. The cytochrome was very autoxidizable and its redox potential at pH 8.0 was -75 mV. Cytochrome b-562 showed absorption peaks at 417 and 530 nm in the oxidized form and peaks at 431, 531, and 562 nm in the reduced form. The cytochrome was composed of only one polypeptide (25 kDa) and seemed to contain one protoheme molecule per molecule. PMID- 8454575 TI - Molecular conformation of porcine amelogenin in solution: three folding units at the N-terminal, central, and C-terminal regions. AB - Circular dichroism (CD) studies were conducted to gain a better insight into the conformation of amelogenins, which were isolated from developing enamel of piglets. The intact porcine amelogenin and its degraded products were purified chromatographically. The 25-residue peptide corresponding to the segment at the C terminus was synthesized. CD spectra of these samples were measured at pH 5.0-5.3 in the temperature range between 4 and 90 degrees C. The most remarkable finding was that the CD spectrum of the intact amelogenin was accounted for by the sum of the spectra of the three fragments at the N-terminal, central, and C-terminal regions, supporting the hypothesis that the structure of the whole protein consists of discrete folding units. Furthermore, low-angle laser light scattering analysis provided evidence that the 20 kDa amelogenin, the most abundant extracellular matrix protein in forming enamel tissue, exists in a monomeric form at pH 5.3 and 25 degrees C. It was tentatively concluded that the N-terminal region contains beta-sheet structures, while the spectral characteristics of the C-terminal region are similar to those of a random coil conformation. The conformation of the central region was characterized by a strong negative ellipticity at 203 nm, although its nature remains to be defined. PMID- 8454576 TI - An isozyme of microsomal carboxyesterases, carboxyesterase Sec, is secreted from rat liver into the blood. AB - It is generally believed that liver carboxyesterases are localized exclusively in the endoplasmic reticulum (ER), mostly in the lumen, loosely bound to the inner side of the membrane. A cDNA clone, clone (8-1/2-1) supposed to code for one of the isozymes, carboxyesterase E1, was isolated by Takagi et al. [J. Biochem. 104, 801-806 (1988)]. However, the protein coded by clone (8-1/2-1) had no consensus ER retention signal at its carboxy terminus, and the mechanism of its retention by ER lumen was unclear. When clone (8-1/2-1) was expressed in COS cells in this study, the plasmid-coded protein was secreted into the medium. When the carboxy terminal portion of the clone (8-1/2-1)-coded protein was replaced with the corresponding region of another carboxyesterase, pI 6.1 esterase, which had the HVEL sequence at the carboxy terminus, the chimeric protein was retained in the COS cells. We searched for a secretory form carboxyesterase in rat blood immunochemically using polyclonal antibodies to carboxyesterase E1, and detected a cross-reacting protein with a molecular weight of 68 kDa. The molecular weight was decreased by endoglycosidase F treatment but not by endoglycosidase H treatment, indicating that the protein carries complex type sugar chains. In addition, the cross-reacting protein was labeled with [3H] diisopropylfluorophosphate (DFP), suggesting that the protein has an esterase type active center serine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454578 TI - Effects of point mutation in a flexible loop on the stability and enzymatic function of Escherichia coli dihydrofolate reductase. AB - To elucidate the role of a flexible loop in the stability and function of Escherichia coli dihydrofolate reductase, glycine-121 in the flexible loop (117 131) was substituted to valine and leucine by site-directed mutagenesis. Despite the increased hydrophobicity of the side chains, the free energy changes of unfolding of the two mutants (G121V and G121L) determined by urea denaturation at 15 degrees C were decreased by 1.22 and 0.38 kcal/mol, respectively, compared with that of the wild-type. Thermal denaturation temperature, as monitored by differential scanning calorimetry, was decreased by 2.4 and 5.2 degrees C for G121V and G121L, respectively, accompanying the decrease in enthalpy change of denaturation. These findings indicate that the structure of DHFR is destabilized by the mutations, predominantly due to the large decrease in enthalpy change of denaturation relative to entropy change of denaturation. The steady-state kinetic parameter in the enzyme reaction, Km, was not influenced but kcat was greatly decreased by these mutations, resulting in 240- and 52-fold decreases in kcat/Km for G121V and G121L, respectively. The main effect of the mutations appeared to be modification of the flexibility of the loop due to overcrowding of the bulky side chains, overcoming the enhancement of hydrophobic interaction. PMID- 8454580 TI - Interaction between pullulanase from Klebsiella pneumoniae and cyclodextrins. AB - The interaction between pullulanase from Klebsiella pneumoniae and alpha-, beta-, and gamma-cyclodextrins and 6-O-alpha-glucosyl-alpha-cyclodextrin and 6-O-alpha glucosyl-beta-cyclodextrin was examined by means of inhibition studies of the enzyme activity, UV difference spectroscopy, and flow calorimetry. All the above cyclodextrins were found to be competitive inhibitors, but beta-cyclodextrin and 6-O-alpha-glucosyl-beta-cyclodextrin showed strong inhibition, the inhibitor constants being two orders of magnitude less than those of alpha- and gamma cyclodextrins. The difference spectra of beta-cyclodextrin were slightly but significantly different from those of the other cyclodextrins, showing blue shift of a few nanometers. Moreover, only beta-cyclodextrin has a positive entropy change upon binding with the enzyme; all the other cyclodextrins have negative values. These results show that the binding mode of beta-cyclodextrin is subtly different from those of alpha- and gamma-cyclodextrins. PMID- 8454577 TI - Replacement of Thr-303 of P450 2E1 with serine modifies the regioselectivity of its fatty acid hydroxylase activity. AB - Threonine-303 of rabbit P450 2E1, which is putatively located at the distal heme surface, was replaced by serine and valine via site-directed mutagenesis. In the oxidized state, the Ser-mutated P450 exhibited a low- and high-spin mixed-type (low > high) absorption spectrum, whereas the Val-mutated P450, like the wild type P450, exhibited a nearly high-spin type spectrum. The reduced CO complexes of the Ser- and Val-mutated P450s, as well as that of the wild-type P450, showed a Soret absorption maximum at 452 nm. Both mutated P450s were active in the hydroxylation of C10 to C18 fatty acids at somewhat lower rates than the wild type P450. The Val-mutated P450 gave the same two products (the major one is probably the omega-1 hydroxy analog) as the wild-type P450, while additional products were formed on incubation with C11 to C17 fatty acids as substrates of the Ser-mutated P450; a total of four products was detected for each of the C12 to C15 fatty acids, and three for each of the C11, C16, and C17 homologues. The metabolites of laurate were determined by GC-MS analysis to be the omega-1, omega 2, omega-3, and omega-4 hydroxy counterparts. The Ser-mutated P450 hydroxylated drug substrates at almost the same rates as the wild-type P450, while the mutation to valine significantly lowered the drug hydroxylase activities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454579 TI - Structural analysis of recombinant human carboxy-terminal-truncated macrophage colony-stimulating factor. AB - The recombinant human carboxy-terminal-truncated macrophage colony-stimulating factor ([3-153]M-CSF) consists of 302 amino acid residues and has a molecular mass of about 32 kDa, as estimated by SDS-PAGE. Two covalently linked subunits constitute a bioactive homodimer. The structure of the purified protein, expressed in Escherichia coli and refolded from inclusion bodies, was studied. The amino acid sequence was determined by automated Edman degradation of fragments obtained from degradation with CNBr and iodosobenzoic acid as well as by digestion with Glu-C endopeptidase of reduced and alkylated M-CSF. The absence of free thiol groups in the molecule was confirmed with Ellman reagent, which indicated the presence of seven disulfide linkages per homodimer. Sequence analysis of cystine-containing peptides, identified by comparing the peptide maps from unmodified and performic acid-oxidized pepsin digests, gave the following results. (1) Six out of seven disulfide linkages were formed between Cys 7 and Cys 90, Cys 48 and Cys 139, and Cys 102 and Cys 146 at each pair of positions as either intra- or inter-chain disulfides. (2) The remaining disulfide linkage linked Cys 31 of one subunit to Cys 31 of the second subunit of M-CSF. Based on our findings, a two-dimensional model is proposed in which the possible covalent linkage is suggested between the two subunits of the bioactive [3-153]M-CSF molecule. PMID- 8454581 TI - Corrinoid specificity of cytosolic cobalamin-binding protein of Euglena gracilis z. AB - To elucidate the corrinoid specificity of the cytosolic cobalamin-binding protein of Euglena gracilis, inhibition of the binding of radioactive cyanocobalamin to the cytosolic binding protein was studied with a variety of cobalamin analogues. The cytosolic cobalamin-binding protein showed an absolute requirement for the alpha-axial ligand (the cobalt-coordinated nucleotide) in cobalamin binding, but was not able to recognize certain differences in the base or ribose moiety. Regarding the contributions of the b-, d-, and e-propionamide side chains in the binding of cobalamin to the cytosolic protein, the order of the contributions was shown to be b > d > e; in particular the b-propionamide side chain was essential for the formation of the protein-cobalamin complex. No involvement of the beta axial ligand or the alkanolamine group in the binding of cobalamin to the protein was found. PMID- 8454582 TI - The multicatalytic and 26 S proteases. PMID- 8454583 TI - Overexpression of protein kinase C-delta and -epsilon in NIH 3T3 cells induces opposite effects on growth, morphology, anchorage dependence, and tumorigenicity. AB - We have determined the patterns of mRNA and protein expression of 7 protein kinase C (PKC) isozymes in NIH 3T3 cells. Only PKC-alpha is expressed abundantly in NIH 3T3 cells; endogenous levels of the other 6 PKC isozymes are low or undetectable. We have overexpressed PKC-delta and -epsilon in these cells to observe activation/translocation of these two isozymes and the biological consequences of overexpression. Both PKC-delta and -epsilon, but not PKC-alpha, are partially associated with the insoluble fraction even in the absence of phorbol 12-myristate 13-acetate (PMA). Upon PMA stimulation, both PKC-delta and epsilon translocate to the insoluble fraction of cell homogenates, as can be observed with the endogenous PKC-alpha. Overexpression of PKC-delta induces significant changes in morphology and causes the cells to grow more slowly and to a decreased cell density in confluent cultures. These changes are accentuated by treatment with PMA. Overexpression of PKC-epsilon does not lead to morphological changes, but causes increased growth rates and higher cell densities in monolayers. None of the PKC-delta overexpressers grow in soft agar with or without PMA, but all the cell lines that overexpress PKC-epsilon grow in soft agar in the absence of PMA, but not in its presence. NIH 3T3 cells that overexpress PKC-epsilon also form tumors in nude mice with 100% incidence. This indicates that high expression of PKC-epsilon contributes to neoplastic transformation. PMID- 8454586 TI - Production of crystallizable cruzain, the major cysteine protease from Trypanosoma cruzi. AB - The major cysteine protease of Trypanosoma cruzi, cruzain, has been previously expressed in Escherichia coli as a fusion polypeptide. The proteolytic processing events required to obtain active, mature cruzain from the recombinant expression system have been characterized using mutational analysis of the cloned gene. An inactive variant of cruzain (cruzain-C25A) revealed that the proteolytic cleavage of the COOH-terminal domain from the recombinant cruzain is independent of cruzain activity. This cleavage event, presumably performed by another protease, was reduced, although not completely eliminated, in a variant in which the cleavage recognition site was altered (cruzain-E219P). To obtain a homogeneous COOH terminus of the recombinant enzyme, a truncated form of cruzain (cruzain delta c) was engineered by insertion of a stop codon in the gene at a site corresponding to autoproteolysis observed with the native enzyme, purified from epimastigotes. Diffraction quality crystals of recombinant cruzain (cruzain) and the truncated variant (cruzain-delta c) have been produced and characterized. Cruzain and cruzain-delta c were cocrystallized with the peptide fluoromethyl ketone (FMK) inhibitors, Z-Phe-Arg-FMK and Z-Phe-Ala-FMK, respectively, (where Z is benzyloxycarbonyl). The crystals are monoclinic, space group P2(1), with a = 45.5 A, b = 51.0 A, c = 45.7 A, and beta = 116.1 degrees. One cruzain molecule is present in the asymmetric unit. The crystallographic data reveal that the high resolution structure determination is feasible. This system will facilitate the three-dimensional structure determinations and biochemical analyses of cruzain and cruzain variants. PMID- 8454584 TI - Old Yellow Enzyme. The discovery of multiple isozymes and a family of related proteins. AB - Using fast protein liquid chromatography, we have separated native Old Yellow Enzyme from Brewer's Bottom Yeast into three distinct fractions. Two of these fractions are homodimeric forms of the enzyme while the third is the corresponding heterodimeric form. One of these homodimeric fractions is identical in every respect to OYE1, originally cloned from Brewer's Bottom Yeast (Saito, K., Thiele, D. J., Davio, M., Lockridge, O., and Massey, V. (1991) J. Biol. Chem. 266, 20720-20724). We have cloned, sequenced, and expressed a second Old Yellow Enzyme gene from Saccharomyces cerevisiae, showing close similarity, but not identity, with OYE1. Native Old Yellow Enzyme samples were also affinity-purified from a strain of S. cerevisiae and an OYE deletion mutant constructed from it. A total of at least seven isozymes of Old Yellow Enzyme have been discovered, each having slightly different characteristics ranging from surface charge to NADPH dehydrogenase activities with different electron acceptors, as well as N-terminal amino acid sequence. In addition, both recombinant enzymes showed considerable similarity to two proteins in the GenBank/EMBL data bank, a 60,000-dalton bile acid-inducible polypeptide in Eubacterium sp. (Mallonee, D. H., White, W. B., and Hylemon, P. B. (1990) J. Lipid Res. 172, 7011-7019) and a 72,000-dalton NADH oxidase in Thermoanaerobium brockii. PMID- 8454587 TI - Thermal stability and cooperative domains of CPL1 lysozyme and its NH2- and COOH terminal modules. Dependence on choline binding. AB - Differential scanning calorimetry (DSC) has been employed to characterize the thermal denaturation of CPL1 lysozyme and its isolated fragments in the absence and presence of choline. The heat capacity function of CPL1 lysozyme shows two peaks with Tm values of 43.5 and 51.4 degrees C. At saturating concentrations of choline the second transition disappears, and the Tm is shifted to higher temperatures. The DSC thermogram of the C-CPL1 protein corresponding to the carboxyl-terminal domain of CPL1 lysozyme has a single peak with a Tm of 42.9 degrees C. The effect of choline is very similar to that observed for the whole CPL1 lysozyme. The NH2-terminal fragment obtained by proteolytic digestion shows a Tm of 52 degrees C, close to that of 51.4 degrees C found for the second transition of CPL1, and choline does not affect the Tm nor the denaturation enthalpy. These data suggest that choline is bound to the COOH-terminal domain of the protein. Deconvolution of the excess heat capacity curve of the CPL1 lysozyme shows that the data can be fitted to two two-state independent transitions. The analysis of the DSC curves showed that the NH2-terminal unfolding enthalpy steadily decreases with increasing concentrations of choline. These results indicate that, under saturating concentrations of choline, whole CPL1 could unfold as a single cooperative unit. PMID- 8454588 TI - Cloning, overexpression, and genomic mapping of the 14-kDa subunit of human replication protein A. AB - Replication protein A (RPA) is a three-subunit protein that plays a central role in eukaryotic DNA replication, recombination, and repair. We have previously reported the cloning and bacterial expression of the 70- and 32-kDa subunits of human RPA (hRPA). We have now cloned the 14-kDa subunit (hRPA3) from a HeLa cell cDNA library. The hRPA3 cDNA is a 692-base pair sequence that contains an open reading frame encoding a protein of 121 amino acids with a calculated molecular mass of 13.6 kDa. The deduced amino acid sequence shows only limited similarity to the small subunit of yeast RPA and is unrelated to any other protein in the current data banks. A recombinant protein containing a short histidine tag at the NH2 terminus has been purified in good yield from Escherichia coli by metal chelate affinity chromatography. Antibodies prepared against recombinant hRPA3 recognize the native protein and inhibit SV40 DNA replication in vitro. We have localized the genes for the 70-, 32-, and 14-kDa subunits to chromosomes 17, 1, and 7, respectively, using polymerase chain reaction amplification of genomic DNA from rodent-human hybrid cell lines. Since RPA appears to be involved in several fundamental cellular processes, the physical mapping of the RPA genes may be useful in identifying possible human genetic defects associated with RPA deficiency or dysfunction. PMID- 8454589 TI - Cell-CAM105 isoforms with different adhesion functions are coexpressed in adult rat tissues and during liver development. AB - The rat hepatocyte cell adhesion molecule cell-CAM105 has recently been shown to be composed of at least two isoforms. Expression of the two isoforms in different tissues and during fetal liver development in rats was studied by RNase protection using a probe which could specifically and simultaneously detect both isoforms. This probe revealed protected fragments of expected lengths for the L form and the S-form in RNA samples isolated from various adult rat tissues. High levels of the L-form and S-form messages were detected in liver and intestine, moderate levels were detected in lung, and weak signals were detected in muscle, kidney, and spleen. In liver development studies, the messages for cell-CAM105 showed a major increase on the first day after birth compared to the fetal stage, and both isoform messages were proportionally increased. These results indicate that both cell-CAM105 isoforms may have function(s) related to hepatocyte differentiation. To study the adhesion function of cell-CAM105 isoforms, full length cDNAs for these isoforms were expressed in insect cells. The insect cells expressing the L-form cell-CAM105 were found to aggregate. However, expression of S-form cell-CAM105 did not support cell aggregation. These results indicate that L-form, but not S-form, cell-CAM105 directly mediates the cell adhesion function. PMID- 8454595 TI - Structural aspects of inotropic bipyridine binding. Crystal structure determination to 1.9 A of the human serum transthyretin-milrinone complex. AB - The crystal structure of human transthyretin (TTR) complexed with milrinone (2 methyl-5-cyano-3,4'-bipyridin-6(1H)-one), a positive inotropic cardiac agent, has been refined to R = 17.4% for 8-1.9-A resolution data. This report provides the first detailed description of protein interactions for an inotropic bipyridine agent which is an effective thyroid hormone binding competitor to transthyretin. Milrinone is bound along the 2-fold axis in the binding site with its substituted pyridone ring located deep within the channel of the two identical binding domains of the TTR tetramer. In this orientation the 5-cyano group occupies the same site as the 3'-iodine in the TTR complex with 3,3'-diiodothyronine (Wojtczak, A., Luft, J., and Cody, V. (1992) J. Biol. Chem. 267, 353-357), which is 3.5 A deeper in the channel than thyroxine (Blake, C. C. F., and Oately, S. J., (1977) Nature 268, 115-120). These structural results confirm computer modeling studies of milrinone structural homology with thyroxine and its TTR binding interactions and explain the effectiveness of milrinone competition for thyroxine binding to TTR. To understand the weaker binding affinity of the parent inotropic drug, amrinone (5-amino-3,4'-bipyridin-6(1H)-one), modeling studies of its TTR binding were carried out which indicate that the 5-amino group cannot participate in strong interactions with TTR and the lack of the 2-methyl further weakens amrinone binding. PMID- 8454594 TI - Identification of the regulatory site in smooth muscle calponin that is phosphorylated by protein kinase C. AB - F-actin and tropomyosin inhibited the phosphorylation of calponin by protein kinase C, and the phosphorylation reduced the binding of calponin to F-actin and tropomyosin. Labeled phosphate from [gamma-32P]ATP was retained both on the chymotryptic NH2-terminal 22-kDa fragment, which contains the actin-, tropomyosin , and calmodulin-binding regions, and on the COOH-terminal 12-kDa fragment. Fractionation of tryptic 32P-labeled peptides by high performance liquid chromatography allowed isolation of three phosphopeptides (designated T1, T2, and T3), each of which was located in three repeating amino acid motifs of calponin. Both the relative initial rates and extent of phosphorylation decreased in the order T2 > T3 > T1. Both serine and threonine residues were phosphorylated in T1 (GASQAGMTAPGTK), and only a threonine residue was phosphorylated in T2 (FASQQGMTAYGTR) and in T3 (GASQQGMTVYGLPR). As the 22-kDa fragment contained only T2, the phosphorylation site in T2 appeared to regulate the binding of calponin to F-actin and tropomyosin. The amino acid sequence of T2 indicates that protein kinase C phosphorylates Thr184. Thus Thr184 is the preferred site of phosphorylation and is functionally the most important of the sites phosphorylated by protein kinase C in smooth muscle calponin. PMID- 8454590 TI - Modification of sulfhydryl groups of interleukin-8 (IL-8) receptor impairs binding of IL-8 and IL-8-mediated chemotactic response of human polymorphonuclear neutrophils. AB - Interleukin-8 (IL-8), a monocyte-derived neutrophil chemotactic agent, has a potential role in the regulation of inflammatory responses. The specific receptor for IL-8 has been identified and characterized on the surface of human neutrophils (Samanta, A. K., Oppenheim, J. J., and Matsushima, K. (1989) J. Exp. Med. 169, 1185-1189). The present study demonstrates that at least two sulfhydryl groups of this receptor from human neutrophils participate in the binding of IL 8. Incubation of neutrophils with sulfhydryl group-modifying reagents, N ethylmaleimide and diazene dicarboxylic acid bis-N,N-dimethylamide (diamide), severely impaired the binding of 125I-IL-8 to neutrophils. Treatment with 0.8 mM N-ethylmaleimide and 0.4 mM diamide inhibit binding of 125I-IL-8 to the neutrophils by 62 and 60%, respectively. These inhibitory effects could be reversed by 84-87% by treatment with 2-4 mM dithiothreitol. The saturable amount of the ligand, IL-8, provided partial protection against the modifying reagents. N-Ethylmaleimide and diamide at a concentration of 0.4 mM reduced chemotactic migration of neutrophils in a Boyden chamber by 95 and 60%, respectively. At a concentration of 0.4 mM, N-ethylmaleimide reduced the IL-8-induced (10 micrograms/ml) release of myeloperoxidase by 50%. Under identical conditions, 0.4 mM diamide could reduce release of myeloperoxidase by 63%. Finally, N ethylmaleimide severely affected the overall binding and total uptake of 125I-IL 8 to the neutrophils at 37 degrees C, a condition required for receptor-mediated internalization of the ligand and recycling of the receptor to the surface of neutrophils. Nitro blue tetrazolium reduction test of the lipopolysaccharide stimulated neutrophils indicates that compared to control general metabolic functions of thiol-modified cells were markedly retained. These data suggest that at least two conformationally vicinal free reactive sulfhydryl groups are located in the binding domain of the receptor in neutrophils which are essential for IL-8 mediated biological responses. PMID- 8454592 TI - Studies on the mechanism of oxidative phosphorylation. ATP synthesis by submitochondrial particles inhibited at F0 by venturicidin and organotin compounds. AB - Oligomycin,N,N'-dicyclohexylcarbodiimide (DCCD), venturicidin, and tetracoordinate organotin compounds (R3SnX) are potent inhibitors of the mitochondrial ATP synthase complex, all acting on the membrane sector, F0. Oligomycin and DCCD inhibit proton translocation through F0 and energy transfer between F0 and the catalytic sector, F1, of the ATP synthase complex. Our results have shown that venturicidin and organotin compounds (tributyltin and triphenyltin chloride were used) greatly attenuate these processes, but do not cause complete inhibition. As a result, bovine submitochondrial particles (SMP) treated with venturicidin or tributyltin chloride were shown to be capable of ATP hydrolysis and synthesis, albeit at very slow rates. We had shown previously that in ATP synthesis Vmax and apparent Km for ADP and Pi increase or decrease, respectively, as the steady-state membrane potential is elevated or lowered (Matsuno-Yagi, A., and Hatefi, Y. (1986) J. Biol. Chem. 261, 14031-14038). These changes occurred at constant Vmax/Km, suggesting that the apparent Km changes were due mainly to kcat changes. Results presented here show that, in respiring SMP treated with venturicidin or organotin compounds, the membrane potential is near the static-head level, but the slow rate of ATP synthesis takes place with a low KmADP value of 2-3 microM. In agreement with our previous conclusions, these results indicate that it is not the membrane potential per se that affects KmADP during ATP synthesis, but rather it is the rate of energy transfer from F0 to F1 that influences both Vmax and KmADP. Further conclusions from the above studies have been discussed in relation to the possible mechanism of energy transfer between F0 and F1 and the manner in which venturicidin and organotin compounds might attenuate this process. PMID- 8454591 TI - Transcriptional regulation of TSG6, a tumor necrosis factor- and interleukin-1 inducible primary response gene coding for a secreted hyaluronan-binding protein. AB - TSG6 was originally identified as a tumor necrosis factor (TNF)-inducible gene in human fibroblasts. Earlier we showed that the secretory TSG6 protein is a member of a family of hyaluronan-binding proteins that includes cartilage link protein, proteoglycan core protein, and the adhesion receptor CD44. In the present study we have used Southern blot analysis to demonstrate that TSG6 is a single-copy gene in the human and murine species. With the aid of a somatic cell hybrid mapping panel, TSG6 was assigned to human chromosome 2. Nuclear run-on analysis revealed that TNF produced a rapid, primary transcriptional activation of the TSG6 gene in normal human FS-4 fibroblasts. In order to learn more about the regulation of TSG6 gene expression, we cloned the TSG6 gene from a genomic library of human white blood cells. Sequencing of a 1.3-kilobase fragment of the 5'-flanking region of the TSG6 gene identified TATA-like and CAAT sequences near the transcription start site. In addition, potential binding sites for NF-IL-6, AP-1, interferon regulatory factors (IRF)-1 and -2, and glucocorticoid response elements were identified in the 5'-flanking region. A single transcription start site was identified by primer extension. Deletion analysis of the 5'-flanking region of the TSG6 DNA linked to the chloramphenicol acetyltransferase reporter gene revealed that a construct containing TSG6 DNA from positions -165 to +78 could be transcriptionally activated by interleukin(IL)-1, and to a lesser extent by TNF, upon transfection into FS-4 fibroblasts. The region that imparts inducibility by IL-1 or TNF (positions -165 to -58) contains potential binding sites for IRF-1 and -2, AP-1, and NF-IL-6. A region mediating transcriptional silencing was localized further upstream (between positions -332 and -165). The results suggest that TSG6 gene expression is regulated by an interplay of positively and negatively acting transactivating factors. PMID- 8454598 TI - Lipopolysaccharide of Campylobacter coli serotype O:30. Fractionation and structure of liberated core oligosaccharide. AB - Lipopolysaccharide from phenol-water extraction of cells of Campylobacter coli serotype O:30 was separated as a water-insoluble gel of low M(r) from a water soluble antigenic polysaccharide of high M(r). Acetic acid hydrolysis of the ketosidic linkages to lipid A in the lipopolysaccharide furnished a core oligosaccharide. Structural investigations were performed using 1H and 13C NMR, fast atom bombardment-mass spectrometry of permethylated derivatives, and methylation linkage analysis on the core oligosaccharide and the products of two successive Smith degradations. It is concluded that the highly branched 3-deoxy-D manno-octulosonic acid-terminated oligosaccharide chains carried at the nonreducing end disaccharide units of beta-D-Qui3NAc-(1-->2)-beta-D-Qui3NAc (where Qui3NAc represents 3-acylamino-3,6-dideoxy-D-glucose), in which N-acyl residues were either both (R)-3-hydroxybutanoyl or both 3-hydroxy-2,3-dimethyl-5 oxoprolyl. The demonstration of these unusual features provides further evidence for a wide variety of structures within the core oligosaccharide region of lipopolysaccharides from Campylobacter sp. PMID- 8454585 TI - Procollagen binding to sphingomyelin. AB - The interactions of [3H]procollagen I with various phospholipids were studied by density gradient centrifugation. At physiological conditions of pH, ionic strength, and temperature, there was no evidence for procollagen binding to phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, or phosphatidylserine liposomes. In contrast, procollagen I bound strongly to sphingomyelin liposomes in a reversible and saturable manner, with an apparent dissociation constant (Kd) of 2.6 nM. Binding occurred over a range of temperatures (4-37 degrees C) and was relatively unaffected by salt concentrations up to 1.2 M NaCl. Binding was observed in phosphate buffers, but not in the presence of high concentrations of Tris or Hepes. Bovine serum albumin had no effect on procollagen binding to sphingomyelin, and neither did unlabeled type I collagen, with or without the nonhelical telopeptides. Procollagen II and denatured procollagen I also bound to sphingomyelin. Procollagen binding to sphingomyelin at 35 degrees C was considerably reduced when small amounts of phosphatidylcholine were present, although binding was partially restored when the temperature was reduced below the corresponding phase transition temperature. Purified unlabeled procollagen COOH-terminal propeptides successfully competed for binding, and 125I-labeled COOH-terminal propeptides bound to sphingomyelin in the absence of procollagen. Weaker binding to sphingomyelin, mediated by the collagen triple helical region, was also observed; but this was dominated by the sphingomyelin-COOH-terminal propeptide interaction. The data suggest a novel mechanism for matrix vesicle-mediated biomineralization. PMID- 8454597 TI - Combined application of site-directed mutagenesis, 2-azido-ATP labeling, and lin benzo-ATP binding to study the noncatalytic sites of Escherichia coli F1-ATPase. AB - Noncatalytic nucleotide sites of Escherichia coli F1-ATPase were studied by site directed mutagenesis, covalent photolabeling with 2-azido-ATP, and lin-benzo-ATP binding. In wild-type, 89% of 2-azido-ATP label was bound to beta-subunit, whereas in the beta Y354F mutant, 95% of the label was bound to alpha-subunit. In the alpha R365Y mutant, label was seen on both alpha (38%) and beta (62%); whereas in the alpha R365F mutant, 93% was on beta. The fluorescence of noncatalytic site-bound lin-benzo-ATP was quenched markedly in F1 from wild-type (76% quench), alpha R365F (85%), alpha R365Y (90%), and alpha R365Y, beta Y354F (83%), but only by 28% in beta Y354F. These results together demonstrate that residues alpha R365 and beta Y354 lie close to the base moiety of adenine nucleotide bound in F1 noncatalytic sites. From comparison of sequences of alpha- and beta-subunits, it appears that residue alpha R365 in noncatalytic sites is equivalent to residue beta Y331 of the catalytic sites. Two unintended mutants were obtained in which alpha-subunit was increased in length by 17 amino acids due to repeat of residues alpha 361 to alpha 377, with either F or Y in the repeated alpha 365 position. Soluble F1 was obtained from both mutants, with novel properties. PMID- 8454596 TI - Phosphorylase kinase phosphorylates the calmodulin-binding regulatory regions of neuronal tissue-specific proteins B-50 (GAP-43) and neurogranin. AB - Neuronal tissue-specific proteins B-50 (GAP-43, neuromodulin) and neurogranin are phosphorylated by phosphorylase kinase with stoichiometries of 0.4 and 0.5 mol of phosphate/mol of protein, respectively. The apparent Km and kcat values determined at pH 8.2 for neurogranin phosphorylation are 28.4 microM and 139.3 min-1, respectively, and for B-50 phosphorylation are 22.8 microM and 33.2 min-1, respectively. As a substrate of phosphorylase kinase, phosphorylase is approximately 44 and approximately 13 times better than B-50 and neurogranin, respectively. Both proteins are better substrates of protein kinase C than of phosphorylase kinase and are phosphorylated on a single site by phosphorylase kinase. The sequence analyses of tryptic phosphopeptides isolated from neurogranin and B-50 phosphorylated by phosphorylase kinase revealed the same amino acid sequence, IQASF, indicating that phosphorylase kinase phosphorylates the calmodulin-binding regulatory regions of B-50 and neurogranin previously known to be phosphorylated by protein kinase C (Coggins, P. J., and Zwiers, H. (1989) J. Neurochem. 53, 1895-1901; Baudier, J., Deloulme, J. C., Dorsselaer, A. V., Black, D., and Matthes, W. D. (1991) J. Biol. Chem. 266, 229-237). In rat brain synaptosomes, a relatively high phosphorylase kinase specific activity is detected, and approximately 32% activity is associated with synaptic membranes where B-50 is localized. In rat brain homogenate and synaptosomal membranes, phosphorylation of a protein that co-migrates with B-50 on SDS-polyacrylamide gel electrophoresis is enhanced in the presence of exogenous phosphorylase kinase. PMID- 8454593 TI - Accumulation of substrates for protein L-isoaspartyl methyltransferase in adenosine dialdehyde-treated PC12 cells. AB - Protein isoaspartyl methyltransferase is implicated in the repair of age-damaged proteins containing atypical, isoaspartyl linkages. To test the prediction that isoaspartyl proteins would accumulate during methyltransferase inhibition, rat PC12 cells were treated with the indirect methylation inhibitor, adenosine dialdehyde. We observed a marked, dose- and time-dependent, reversible accumulation of substrates for the enzyme that closely paralleled the elevation of its competitive inhibitor, S-adenosylhomocysteine. The accumulation of substrates also paralleled a cytostatic action of adenosine dialdehyde; however, 30 microM 3-deazaadenosine, another indirect methylation inhibitor, also caused an accumulation of substrates without affecting cell division, and other cytostatic agents did not affect substrate levels. Acidic gel electrophoresis revealed increased methyl-accepting capacity in a broad spectrum of proteins, with predominant increases in discrete bands of M(r) 46,000 and 110,000. A major substrate (M(r) 17,400) in untreated cells did not increase in methyl-accepting capacity during treatment. Methyl groups at the accumulated sites did not survive conventional electrophoresis, indicating the lability characteristic of isoaspartyl methyl esters in damaged proteins. These results are consistent with an involvement of the methyltransferase in the metabolism of damaged proteins, and they provide a basis for the characterization of physiological substrates for the enzyme. PMID- 8454601 TI - Selenoenzymes regulate the activity of leukocyte 5-lipoxygenase via the peroxide tone. AB - The variation of the selenium status of leukocytes was used as a tool to investigate the influence of selenium-containing glutathione peroxidases on the formation of 5-lipoxygenase metabolites in vitro and ex vivo. Selenium-deficient rat basophilic leukemia cells had < 1% of control glutathione peroxidase activity and 35% of control phospholipid hydroperoxide-glutathione peroxidase activity. Upon stimulation, these cells released an 8-fold amount of lipoxygenase metabolites compared to controls. No (5S)-hydroperoxyeicosatetraenoic acid was detectable in whole cells; however, it was found in homogenates of selenium deficient cells. Addition of 0.25 microgram/ml selenium to selenium-deficient cells restored control phospholipid hydroperoxide-glutathione peroxidase activity within 8 h, whereas glutathione peroxidase activity needed 7 days. 12 h after resupplementation, selenium-deficient cells had 3% glutathione peroxidase and 100% phospholipid hydroperoxide-glutathione peroxidase activity compared to controls. Resupplemented cells released control amounts of 5-lipoxygenase metabolites, indicating that restoration of phospholipid hydroperoxide glutathione peroxidase activity is associated with a selenium-adequate leukotriene metabolism. Leukocytes that were isolated from selenium-deficient rats released a 7-fold amount of total lipoxygenase metabolites compared to cells from control animals. By injecting normally fed rats with 500 micrograms/kg selenium as Na2SeO3, leukocyte phospholipid hydroperoxide-glutathione peroxidase activity was raised 8-fold within 114 h compared to controls. Leukocytes from these animals produced significantly less lipoxygenase metabolites than controls. These findings indicate that phospholipid hydroperoxide-glutathione peroxidase activity is primarily responsible for the reduction of 5-hydroperoxyeicosate traenoic acid and therefore governs the actual activity of leukocyte 5 lipoxygenase via regulating the tone of endogenous hydroperoxides. PMID- 8454600 TI - Regulation of glycoinositol phospholipid anchor assembly in human lymphocytes. Absent mannolipid synthesis in affected T and natural killer cell lines from paroxysmal nocturnal hemoglobinuria patients. AB - Glycoinositol phospholipid (GPI) anchor structures derive from sequentially glycosylated inositol phospholipid precursors assembled in the endoplasmic reticulum. To characterize GPI biosynthesis in nontransformed human lymphocytes and to define the GPI synthetic defect underlying deficient expression of GPI anchored proteins by paroxysmal nocturnal hemoglobinuria (PNH) cells, putative intracellular GPI intermediates were analyzed following [3H]Man labeling of normal and affected lymphocytes. In unstimulated normal peripheral blood lymphocytes, [3H]Man incorporation into GPIs was minimally detectable but after phytohemagglutinin (PHA), allogeneic cell, or anti-CD3 stimulation, assembly of [3H]Man-labeled GPIs markedly increased. Expression of GPIs by prestimulated quiescent PHA blasts could be efficiently induced by phorbol 12-myristate 13 acetate (PMA) and increased by the Ca2+ ionophore A23187 independently of new protein synthesis. Utilizing allogeneically stimulated cells in conjunction with PMA induction, products deriving from [3H]Man labeling of affected CD48- T and natural killer lymphocyte cell lines from five PNH patients were compared to those deriving from unaffected CD48+ cell lines from the same patients or controls. In contrast to unaffected paired control cells, affected cells of all of the patients exhibited a common abnormality in which they assembled dolichol phosphoryl-Man but failed to express [3H]Man-containing GPIs. These data indicate that 1) significant GPI production in lymphocytes is dependent on prior stimulation of the cells, 2) exposure of lymphocytes to agents which activate protein kinase C induces GPI synthesis, and 3) in five PNH patients affected lymphocytes are uniformly defective in an early GPI biosynthetic step which undermines expression of GPI mannolipids. PMID- 8454604 TI - Overexpression of protein kinase C isoenzymes alpha, beta I, gamma, and epsilon in cells overexpressing the insulin receptor. Effects on receptor phosphorylation and signaling. AB - Chinese hamster ovary cells overexpressing the human insulin receptor were transfected with cDNAs encoding protein kinase C isoenzymes alpha, beta I, gamma, and epsilon as well as an inactive alpha. Overexpression of these protein kinase Cs did not affect expression of the insulin receptor or insulin-stimulated tyrosine phosphorylation of the receptor. However, in response to phorbol esters, cells overexpressing isoenzymes alpha, beta I, and gamma, but not epsilon or inactive alpha, exhibited 3-4-fold higher levels of insulin receptor phosphorylation. This increased phosphorylation occurred exclusively on serines and threonine. Tryptic peptide maps indicated that this phosphorylation was primarily on serines 1305/1306 and threonine 1348 as well as several other unidentified sites. This phorbol ester-stimulated phosphorylation did not inhibit activation of the insulin receptor kinase when the receptor was activated in situ but assayed in vitro. However, in cells overexpressing protein kinase C alpha, it did inhibit an in vivo monitor of the activation of the insulin receptor kinase, the insulin-stimulated increase in anti-phosphotyrosine-precipitable phosphatidylinositol 3-kinase activity. These results indicate that increased protein kinase C alpha activity can inhibit insulin-stimulated responses and support the hypothesis that excessive protein kinase C is involved in the insulin resistance observed in non-insulin-dependent diabetics. PMID- 8454602 TI - Formation of epoxyalcohols by a purified allene oxide synthase. Implications for the mechanism of allene oxide synthesis. AB - The allene oxide synthase (hydroperoxide dehydrase) of flaxseed is a cytochrome P450 that exhibits an exceptionally high catalytic turnover (> or = 1000/s) for hydroperoxy substrates. In a previous study, using a crude extract of flaxseed, we detected a secondary activity that could offer an insight into the mechanism of the enzymatic transformation of hydroperoxides. We observed that the substrate 8R-hydroxy-15S-hydroperoxyeicosa-5,9,11,13,17-pentaenoic acid is converted not only to allene oxide, but also to epoxyalcohol derivatives (Brash, A. R., Baertschi, S. W., and Harris, T. M. (1990) J. Biol. Chem. 265, 6705-6712). The transformation of hydroperoxides to epoxyalcohols has been investigated extensively in other systems, and heterolytic or homolytic cleavage of the hydroperoxide is associated with characteristic rearrangements and stereochemistry of the epoxyalcohol products. Using the purified enzyme, we established that the epoxyalcohols are products of the allene oxide synthase. Their structures were determined by UV, gas chromatography-mass spectrometry, and NMR. The major epoxyalcohol is 8R,13R-dihydroxy-14R,15S-epoxyeicosa-5Z,9E ,11Z,17Z-tetraenoic acid, a trans-epoxide with an alpha-hydroxyl in the relative threo configuration. Two minor products are the corresponding 11E isomer and a cis-epoxide identified as 8R,13-dihydroxy-14S,15S-epoxyeicosa-5Z,9E,11E,++ +17Z tetraenoic acid. Gas chromatography-mass spectrometry analysis of a reaction with [18O2]hydroperoxide substrate indicated complete retention of the hydroperoxy oxygens in the epoxyalcohol products. Mechanistic precedents support a homolytic hydroperoxide cleavage as the initial step in the synthesis of these epoxyalcohols. We suggest that the same process initiates allene oxide synthesis, a conclusion that is also most compatible with the known chemistry of cytochromes P450. PMID- 8454608 TI - Cooperative binding of the retinal rod G-protein, transducin, to light-activated rhodopsin. AB - Direct measurements of the binding between light-activated rhodopsin (Rho*) and transducin, the retinal rod G-protein, revealed a strongly cooperative interaction. Cooperativity was assessed by measuring the association of 125I labeled transducin (Gt) to Rho* in urea-stripped rod outer segment membranes at equilibrium. Analysis of 125I-Gt binding curves gave a Hill coefficient of 1.8. These data were consistent with a two-site model in which binding of the first 125I-Gt to Rho* increased the binding of the second 125I-Gt approximately 40-fold (Kd values were 80 +/- 30 and 1.9 +/- 0.7 nM, respectively). The effects of GDP on the binding were also investigated. GDP decreased the affinity between Rho* and Gt approximately 100-fold but did not decrease the degree of cooperativity. Binding curves of 125I-Gt in the presence of 1 mM GDP showed a Hill coefficient of 1.9. The data were also consistent with a two-binding site model in which binding of the first 125I-Gt increased the binding of the second 125I-Gt approximately 70-fold (Kd values were 13.7 +/- 5.4 and 0.20 +/- 0.08 microM, respectively). The Gt alpha subunit in the absence of Gt beta gamma also bound Rho* in a cooperative manner. These data implicate a role for the cooperative association of Rho* and Gt in the light activation cascade of retinal rods. PMID- 8454599 TI - Primary structure of the dihydrofolate reductase-thymidylate synthase gene from Toxoplasma gondii. AB - We have determined the primary genomic and cDNA sequences encoding the bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS) enzyme of the protozoan parasite Toxoplasma gondii (dihydrofolate reductase, EC 1.5.1.3; thymidylate synthase EC 2.1.1.45). The DHFR-TS gene of T. gondii (strain RH) spans more than 6 kilobases of genomic DNA. Unlike the DHFR-TS genes of other protists, sequences encoding the Toxoplasma protein are interrupted by numerous intervening sequences. Analysis of processed T. gondii DHFR-TS cDNAs reveals a single open reading frame of 1830 nucleotides, predicting a 610-amino acid protein of molecular mass of 69 kilodaltons. Because its nucleotide composition and codon usage are roughly comparable to those observed in "higher" eukaryotes, the Toxoplasma DHFR-TS sequence is particularly useful for assessing evolutionary relationships between eukaryotic species. The predicted amino acid sequence for the DHFR-TS protein shows conservation of the major structural features identified in other DHFR and TS enzymes, while revealing certain differences which may be exploited for the design of novel antifolates for treatment of toxoplasmosis associated with AIDS. PMID- 8454605 TI - Transverse localization of the quinacrine binding site on the Torpedo acetylcholine receptor. AB - We demonstrated previously that a phencyclidine-displaceable quinacrine binding site exists at the lipid-protein interface of the Torpedo acetylcholine receptor (AcChR) (Valenzuela, C. F., Kerr, J. A., and Johnson, D. A. (1992) J. Biol. Chem. 267, 8238-8244). In this manuscript, we assess (1) the transverse position of this site in the lipid bilayer by examining the ability of a series of paramagnetic n-doxyl stearates (n-SALs) and iodide to quench receptor-bound quinacrine and membrane-partitioned octadecyl rhodamine B (C18-Rho) fluorescence and (2) the stoichiometry of histrionicotoxin- or phencyclidine-displaceable quinacrine binding. Initial experiments established what fraction of the n-doxyl stearates partitioned into the membranes and that the n-doxyl stearates do not interfere with quinacrine binding to the receptor at the concentrations used in the quenching studies. The n-doxyl stearate quenching experiments indicated relatively small (< 2) differences between the n-doxyl stearates to quench receptor-bound quinacrine fluorescence, with a rank order of 7-SAL > or = 5-SAL > 12-SAL > 16-SAL. This contrasts with the n-doxyl stearate quenching of the membrane-partitioned C18-Rho which showed as much as an 8.6-fold difference between the various isomers with a rank order of quenching efficiencies of 5-SAL > 7-SAL > 12-SAL > or = 16-SAL. Iodide quenching measurements indicated significant solute accessibility to membrane-partitioned C18-Rho but not to receptor-bound quinacrine. The ratios of the bimolecular quenching rate constants for free to bound quinacrine and for free rhodamine B to membrane-partitioned C18 Rho were 53.4 and 6.6, respectively. Direct titration of quinacrine into suspensions of a high concentration of AcChR-associated membranes yielded an upper limit to the binding stoichiometry of 1.4 HTX- or PCP-displaceable quinacrine binding sites/AcChR functional units. The results suggest that there is a single phencyclidine- or histrionicotoxin-displaceable quinacrine binding site located at or somewhat below the level of the C5-C7 in the phospholipid acyl chains at the lipid-protein interface. PMID- 8454603 TI - Transcriptional regulation of interleukin 3 (IL3) in primary human T lymphocytes. Role of AP-1- and octamer-binding proteins in control of IL3 gene expression. AB - We have investigated the molecular and biochemical basis for activation of interleukin 3 (IL3) gene expression in primary human T lymphocytes following CD3 and CD2 receptor stimulation or activation by phytohemagglutinin plus phorbol 12 myristate 13-acetate. Using transfection and reporter gene assays specifically designed for primary T lymphocytes in conjunction with gel retardation assays, Western blot analyses and UV cross-linking studies, we found that c-Jun, c-Fos, and octamer-binding proteins play a major role in transcriptional activation of the IL3 gene via their interaction with two specific regions contained within the IL3 5'-flanking sequence. Additionally, the region between bases -107 and -59 of the IL3 promoter containing putative AP-2 and Sp1 binding motifs appears necessary for basal level expression of the IL3 gene. The data also indicate that CD2 receptor activation and phytohemagglutinin plus phorbol 12-myristate 13 acetate stimulation augment T cell IL3 gene expression through the same cis- and trans-activating signals. These results should contribute to a better understanding of the regulation of IL3 gene expression in human T lymphocytes. PMID- 8454606 TI - A 36-kilodalton tumor-derived factor with myeloid immunomodulatory activity. AB - The conditioned medium from the epidermal carcinoma cell line A431 is shown to inhibit the growth of three human myeloid leukemic cell lines. We have purified to homogeneity from this conditioned medium a 36-kDa protein, as measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, which inhibits [3H]thymidine incorporation into the DNA and induces cell surface expression of CD11b, the alpha chain of the adhesion receptor MAC-1, on the human promyelocytic leukemic cell line HL-60. This factor was purified by sequential anion exchange, hydrophobic interaction, and gel permeation chromatography. Amino acid sequence analysis of two tryptic fragments of the purified material showed greater than 95% homology with sequences 179-194 and 319-328 of the M chain of human L-lactate dehydrogenase. Although the tetrameric L-lactate dehydrogenase alone exhibits no activities associated with the purified 36-kDa protein, brief acid treatment which has been shown to yield predominantly monomeric lactate dehydrogenase-M1 results in about 50% of the maximal antiproliferative activity of that induced by this factor. The role of soluble factors of tumor origin in modulating myeloid function as part of an immunosurveillance network is discussed. PMID- 8454607 TI - Monoclonal anti-idiotypic antibody to a potent thromboxane A2 receptor antagonist and its interaction with thromboxane A2 receptor. AB - A monoclonal anti-idiotypic antibody that interacts with thromboxane A2 receptor was generated using an anti-idiotypic approach. Idiotypic antibodies against a potent receptor antagonist, HS-145, were generated in rabbit. The idiotypic antibodies were then selected by an affinity procedure using SQ29,548-Affi-Gel 102 matrix. The selected idiotypic antibodies were used as surrogate receptor for anti-idiotypic antibody generation. A mouse monoclonal antibody, 3D-9E-12, was generated. It was shown to displace 125I-HS-145 from affinity-purified idiotypic antibodies. It also inhibits 125I-IS-145 binding to thromboxane A2 receptor in human platelet membranes in a dose-dependent manner. Furthermore, it attenuated U46,619-induced increase in [35S]guanosine 5'-O-(thiotriphosphate) binding and GTPase activity in human platelet membranes. Finally, it inhibited U46,619- but not PAF-induced platelet aggregation. These results indicate that 3D-9E-12 acts as a specific antagonist in the thromboxane A2 receptor. PMID- 8454610 TI - Covalent attachment of 4-hydroxynonenal to glyceraldehyde-3-phosphate dehydrogenase. A possible involvement of intra- and intermolecular cross-linking reaction. AB - Cytotoxic action of membrane lipid peroxidation product 4-hydroxynonenal (HNE) is due mainly to its facile reactivity with proteins (Esterbauer, H., Schaur, R. J., and Zollner, H. (1991) Free Radical Biol. Med. 11, 77-80). In the present study, the detailed mechanism of HNE modification of a key enzyme in intermediary metabolism, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), is studied mainly focusing on the formation of HNE-amino acid adducts in the enzyme. When GAPDH (1 mg/ml) was treated with 0-2 mM HNE in sodium phosphate buffer (pH 7.2) for 2 h at 37 degrees C, the enzyme was inactivated by HNE in a concentration-dependent manner. The loss of enzyme activity was associated with the loss of free sulfhydryl groups. Following its reduction with NaBH4, amino acid analysis of the HNE-modified enzyme demonstrated that histidine and lysine residues were also modified. At concentrations lower than 0.5 mM, HNE reacts preferentially with cysteine and lysine residues. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the HNE-modified enzyme suggested the formation of intra- and intermolecular cross-links of the enzyme subunit. The HNE-dependent loss of amino acid residues was accompanied by the generation of protein-linked carbonyl derivatives as assessed by reduction with NaB[3H]H4 and reaction with 2,4 dinitrophenylhydrazine. Thus, the conjugation of all the amino acids appears to involve Michael addition type reactions in which the carbonyl function of HNE would be preserved. The modified histidine residues were quantitatively recovered as the HNE-histidine adduct. However, only 28% of the missing lysine could be accounted for as the HNE-lysine derivative, and only 15.6% of the modified cysteine could be accounted for as the HNE-cysteine thioether derivative. It is proposed that the carbonyl groups of the HNE-derived Michael addition products may undergo secondary reactions with the amino acid groups of lysine residues to yield inter- and intrasubunit cross-links. PMID- 8454609 TI - Interaction of ADP-ribosylation factor with Escherichia coli enterotoxin that contains an inactivating lysine 112 substitution. AB - Cholera toxin and Escherichia coli heat-labile enterotoxin (LT) exert their effects on cells through ADP-ribosylation of guanine nucleotide-binding proteins. Both toxins consist of one A subunit, which is an ADP-ribosyltransferase, and five B (or binding) subunits. Their enzymatic activities are latent; activation requires reduction and proteolysis, resulting in a catalytically active A1 protein and a much smaller A2 protein. These ADP-ribosyltransferases are activated by GTP-dependent 20-kDa ADP-ribosylation factors or ARFs. To determine if proteolysis plus reduction is required for appearance of the ARF allosteric site as well as for catalytic activity, an inactive mutant of LT, LT(E112K), with replacement of glutamate by lysine at position 112 of its A subunit, was utilized as a competitor in cholera toxin ADP-ribosyltransferase assays containing limiting amounts of ARF. LT(E112K) required trypsinization and reduction to become a potent, concentration-dependent inhibitor. Inhibition was reversed by increasing concentrations of ARF. Reduction or trypsinization alone did not generate an inhibitory form of LT(E112K). These studies are consistent with the conclusion that the ARF site is not expressed in the latent toxin. Both trypsinization and reduction are required for expression of a functional ARF binding site as well as for catalytic activity. PMID- 8454613 TI - Comparative study of human and salmon calcitonin secondary structure in solutions with low dielectric constants. AB - Molecular conformations of salmon (sCT) and human (hCT) calcitonin in media with different concentrations of methanol/water and trifluoroethanol/water have been investigated by fluorescence, circular dichroism (CD) and infrared spectroscopy techniques. In these media, sCT and hCT adopt an alpha-helical structure comprising up to 40-48% of the amino acids. CD experiments reveal that for both peptides, the ordering of the Cys1-Cys7 disulfide link and the alpha-helix formation can be distinguished. Disulfide bond ordering is similar in both calcitonins. sCT adopts the alpha-helical structure more readily than hCT, as solvent polarity is reduced. In 2,2,2-trifluoroethanol (TFE)/water mixtures the alpha-helix formation for both hCT and sCT is a two-step process. The first alpha helix formation step occurs at lower TFE concentrations (less than 11 mol% TFE for hCT and 6 mol% TFE for sCT). The second alpha-helix formation step represents 50 and 23% of the whole conformational change for hCT and sCT, respectively. Tyrosine fluorescence measurements correlate with the far ultraviolet CD changes associated with the peptide backbone. hCT is seen to adopt a left-handed, extended conformation in aqueous media below -50 degrees C. PMID- 8454612 TI - Regio- and enantiofacial selectivity of epoxyeicosatrienoic acid hydration by cytosolic epoxide hydrolase. AB - The hydration of cis-epoxyeicosatrienoic acids to the corresponding vic dihydroxyeicosatrienoic acids by cytosolic epoxide hydrolase demonstrates moderate regioselectivity with rates of hydration highest for the 14,15-epoxide and lower for the 11,12- and 8,9-epoxide (4.5, 1.6, and 1.5 mumol of product/mg of protein/min, respectively). Incubations of the 8,9- and 14,15-epoxides with cytosolic epoxide hydrolase show stereoselective formation of diols (7:3 and 4:1 ratio of antipodes, respectively) and concomitant chiral enrichment of the remaining unmetabolized substrate. In contrast, hydration of the 11,12-epoxide is nonenantioselective. The Km value of the enzyme for the 14(R),15(S)-epoxide is 3 microM. Incubations of the enantiomerically pure 8,9- and 14,15-epoxides with lung or liver cytosol, followed by chiral analysis of the resulting diols demonstrate selective cleavage of the oxirane ring at C9 and C15, respectively. On the other hand, cleavage of the 11,12- oxirane ring was less selective. The stereochemical preference of the cytosolic epoxide hydrolase, together with the known chiral composition of the endogenous arachidonate epoxide pools, suggests a functional role for this enzyme in the metabolism of these important compounds. PMID- 8454614 TI - The structure and mechanism of formation of human calcitonin fibrils. AB - Turbidity measurements of the kinetics of human calcitonin (hCT) fibrillation showed a linear dependence of the logarithm of fibrillation time (the time the sample is not fibrillated) and the logarithm of hCT concentration. This ln/ln plot linearity and electron microscope observations of fibrils indicate that the fibrillation process can be explained by the double nucleation mechanism that was proposed for the gelation of sickle cell hemoglobin (Ferrone, F. A., Hofrichter, J., Sunshine, H. R., and Eaton, W. A. (1980) Biophys. J. 32, 361-380). Circular dichroism, fluorescence, and infrared spectroscopy studies of fibrils showed that hCT molecules have alpha-helical and beta-sheet secondary structure components. A model for the structure of hCT molecules in fibrils is proposed. PMID- 8454611 TI - Molecular cloning, expression, and characterization of a 49-kilodalton casein kinase I isoform from rat testis. AB - We report the molecular cloning and characterization of a 49-kDa form of casein kinase I from rat testis. A cDNA clone encoding the enzyme, designated casein kinase I delta, contained an open reading frame of 1284 nucleotides that predicts a polypeptide of 428 amino acids with a M(r) of 49,121. The predicted amino acid sequence shares 76% identity with casein kinase I alpha, a 37-kDa form recently cloned from bovine brain (Rowles, J., Slaughter, C., Moomaw, C., Hsu, J., and Cobb, M. (1991) Proc. Natl. Acad. Sci. U. S. A. 88, 9548-9552), and 65% identity with HRR25, a 57-kDa form of casein kinase I from yeast shown to be involved in DNA repair (Hoekstra, M. F., Liskay, R. M., Ou, A. C., DeMaggio, A. J., Burbee, D. G., and Heffron, F. (1991) Science 253, 1031-1034). Northern analysis of rat or rabbit RNA revealed three hybridizing species of 3.5-4.1, 2.2, and 1.9 kilobase pairs (kb). The largest message was detected in all tissues examined, whereas the 1.9- and 2.2-kb species were found predominantly in testis. A probe corresponding to the 3'-untranslated region of the casein kinase I delta cDNA hybridized only to the 1.9-kb transcript. Expression of the casein kinase I delta cDNA in Escherichia coli resulted in active enzyme that phosphorylated casein, phosvitin, and the peptide substrate DDDDVASLPGLRRR. Enzyme activity was associated with a predominant polypeptide of 55-kDa, although COOH-terminal degradation products of 50 and 42 kDa were also present in partially purified enzyme. Recombinant casein kinase I delta was inhibited by the specific casein kinase I inhibitor, CKI-7, half-maximally at 12 microM. Heparin inhibited recombinant casein kinase I delta when phosvitin was the substrate, with half maximal inhibition at 11.5 micrograms/ml. However, if the peptide substrate was used, heparin activated recombinant casein kinase I delta 4-5-fold, with half maximal activation at 9.5 micrograms/ml. A truncated form of casein kinase I delta, lacking the COOH-terminal 111 amino acids, was no longer activated by heparin. Casein kinase I delta therefore represents a separate member of the casein kinase I family distinguished by its larger size and unique kinetic behavior with respect to heparin. PMID- 8454616 TI - Metabolic control of sugar transport by derepression of cell surface glucose transporters. An insulin-independent recruitment-independent mechanism of regulation. AB - Protein-mediated sugar transport is nominally absent in normoxic pigeon erythrocytes. Following exposure to metabolic inhibitors (cyanide or carbonyl cyanide-p-trifluoromethoxyphenylhydrazone), pigeon red cells transport sugars by a saturable stereoselective pathway that is inhibited by cytochalasin B or forskolin. The sugar transport capacity of fully poisoned cells is consistent with a transporter density of approximately 30 carriers/erythrocyte. Immunoblot analyses and competition enzyme-linked immunosorbent assay indicate that pigeon red cells contain approximately 200 copies of an integral plasma membrane protein immunologically related to the glucose transporter isoform GLUT1. GLUT1 is quantitatively restricted to the plasma membrane at all times. Pigeon red cells and brain lack proteins immunologically related to the sugar transporter isoforms GLUT3 and GLUT4. Specific immunodepletion of red cell GLUT1 content results in the subsequent loss of reconstitutable protein-mediated sugar transport. These findings demonstrate that avian erythrocyte sugar transport is mediated by a GLUT1-like sugar transport protein and that sugar transport stimulation by metabolic depletion results from derepression of cell surface sugar transport proteins. PMID- 8454617 TI - Role of sulfhydryl groups in the function of glucosidase I from mammary gland. AB - Glucosidase I initiates the processing of asparagine-linked glycoproteins by excising the distal alpha 1,2-linked glucosyl residue from the Glc3Man9GlcNAc2 oligosaccharide, soon after its en bloc transfer from the lipid-linked donor to the nascent polypeptide. 1-Deoxynojirimycin, an analog of D-glucose, is a potent competitive inhibitor of the enzyme. Sulfhydryl-seeking reagents also strongly inhibit the enzyme, implying the involvement of an -SH group in its activity. To test this hypothesis, glucosidase I was purified from the rat mammary gland and its active site was loaded with 1-deoxynojirimycin, to protect such a group(s), while -SH groups on the remaining surface of the enzyme were blocked with N ethylmaleimide or para-chloromercuriphenylsulfonic acid. Deoxynojirimycin was removed by dialysis to expose the active site -SH group(s). This group(s) was then tagged with 3-(N-maleimidopropionyl)biocytin (MPB) and detected with 125I streptavidin on Western blots. A series of experiments is presented to show that indeed a critical -SH group(s) is located within the catalytic site of the enzyme. Additionally, the enzyme also possesses one or more sulfhydryls and disulfide bonds in its primary structure. The experimental approach outlined here should apply to identify reactive sulfhydryl groups in other catalytically active proteins. PMID- 8454615 TI - Different behavior of chromatin domains encompassing fibroin heavy-chain gene in active, temporarily inactive, and permanently inactive transcriptional states in silk gland nuclei. AB - Chromatin structures of an approximately 46-kilobase pair region encompassing fibroin heavy chain gene of the silkworm, Bombyx mori, were compared in active (in the posterior silk gland nuclei of the fifth instar larvae), temporarily inactive (in the posterior silk gland nuclei of the fourth molting stage larvae), and permanently inactive (in the middle silk gland nuclei of the fifth instar larvae) transcriptional states. Chromatin structure of the second exon, the major body of the protein-encoding region, was highly sensitive to both DNase I and methidiumpropyl EDTA-Fe(II) in the active state but highly resistant to those agents in both temporarily and permanently inactive states, except that the fibroin "amorphous" region-encoding subregions remained relatively sensitive to DNase I. Distributions of DNase I hypersensitive sites in the 5' upstream region were generally similar between active and temporarily inactive states, but those of the permanently inactive state were markedly different. In the promoter enhancer region, phosphodiester bonds between nucleotide positions -41 and -42 and also -42 and -43 were remarkably hypersensitive to DNase I in the active chromatin, but the same positions in the other two states were not. PMID- 8454618 TI - Inhibition of translational initiation in the yeast Saccharomyces cerevisiae as a function of the stability and position of hairpin structures in the mRNA leader. AB - A new modular in vivo/in vitro expression system was constructed which facilitates studies of the control and regulation of gene expression in the yeast Saccharomyces cerevisiae. We studied the influence of stem-loop structures inserted into the non-translated leader region upon the steady-state levels and translation of mRNAs bearing the cat gene from the bacterial transposon Tn9. mRNA abundance changed relatively little in response to alterations in the leader sequence and structure, whereas stem-loop structures clearly inhibited translation to a degree that was dependent upon the predicted stability as well as the position of the inserted secondary structure. A stem-loop structure with a predicted stability greater than -28 kcal mol-1 and with a stem comprising at least 15 (mainly G/C) base pairs inhibited translation in vivo by at least 98%. A stem-loop structure with a predicted stability of approximately -14 kcal mol-1, whose stem comprised at least six G/C base pairs, inhibited translation in vivo by at least 66%. The hairpins were more inhibitory when placed close to the start codon than when positioned near the 5' end of the leader. An mRNA showing extensive complementarity between the leader and trailer regions was not only poorly translated but also had a steady-state level at least three times higher than the average for all the cat constructs examined. Translation of the various mRNAs in a yeast cell-free system followed qualitatively the same pattern as the results obtained in vivo. The stem-loop structures were far less inhibitory in a reticulocyte lysate system. Overall, the data are likely to reflect the full spectrum of translational activities of yeast mRNAs in vivo determined by secondary structure and emphasize the importance of translation as a control step in gene expression. PMID- 8454619 TI - Role of cytosolic tyrosine kinase in mediating insulin-like actions of vanadate in rat adipocytes. AB - In previous studies we have identified a cytosolic protein tyrosine kinase (CytPTK) in rat adipocytes that is largely activated in vanadate-pretreated cells (Shisheva, A., and Shechter, Y. (1992) FEBS Lett. 300, 93-96). We report here that staurosporine and its analog K-252a are highly potent (ID50 = 3 and 100 nM, respectively) in inhibiting CytPTK activity of crude cell extract or partially purified enzyme preparations. Staurosporine and K-252a were less effective by more than 2 and 1 orders of magnitude, respectively, in inhibiting insulin receptor-catalyzed PolyGlu4Tyr phosphorylation in cell-free experiments. Preincubation of rat adipocytes with either staurosporine or K-252a selectively blocked the action of vanadate in activating glucose incorporation into lipids and its oxidation. Thus, staurosporine inhibited vanadate-stimulated lipogenesis and glucose oxidation (via glycolysis and the pentose phosphate pathway) in a concentration-dependent manner with ID50 of 75 and 300 nM, respectively. Insulin stimulated bioeffects were not inhibited at this low range of staurosporine concentration. Staurosporine had no effect on vanadate-stimulated hexose uptake or on vanadate's antilipolytic action. Using staurosporine, we probed those insulinomimetic agents which facilitate their biological activity via the insulin receptor kinase (insulin, wheat germ agglutinin, concanavalin A, and pervanadate) or via CytPTK (vanadate and to a certain degree Mn2+ and Zn2+). These results suggest that (a) vanadate facilitates its insulin-like actions on glucose utilization via the cytosolic tyrosine kinase and (b) this enzyme does not participate in vanadate effects in stimulating hexose uptake and in inhibiting lipolysis. These findings explain further vanadate's post-insulin receptor actions and raise possible application in the management of glucose metabolism in insulin-independent fashion in pathological conditions. PMID- 8454620 TI - Apoptosis induced by withdrawal of interleukin-3 (IL-3) from an IL-3-dependent hematopoietic cell line is associated with repartitioning of intracellular calcium and is blocked by enforced Bcl-2 oncoprotein production. AB - The regulation of intracellular pools of Ca2+ was investigated in an interleukin 3 (IL-3)-dependent hematopoietic cell line 32D that undergoes programmed cell death ("apoptosis") when deprived of lymphokine. Comparisons were made with 32D cells that had been stably transfected with a bcl-2 expression plasmid that encodes a 26-kDa intracellular integral-membrane protein known to abrogate apoptosis resulting from IL-3 withdrawal. Removal of IL-3 from cultures of 32D cells or control-transfected 32D-NEO cells for 1-2 days led to cell cycle arrest and oligonucleosomal DNA fragmentation and was associated with lower cytosolic free Ca2+ concentrations ([Ca2+]i), as measured by Indo-1 fluorescence of viable cells in Ca(2+)-containing media. In bcl-2-expressing 32D-BCL2 cells, IL-3 withdrawal also resulted in cessation of proliferation, but [Ca2+]i levels were not decreased and DNA fragmentation was markedly suppressed. Nonmitochondrial stores of Ca2+ were also significantly diminished in IL-3-deprived 32D-NEO but not in 32D-BCL2 cells, based on measurements of Ca2+ release into the cytosol following exposure of cells to thapsigargin (an inhibitor of endoplasmic reticulum Ca(2+)-ATPases) under Ca(2+)-free conditions. In contrast, estimates of mitochondrial Ca2+ stores using an uncoupler of oxidative phosphorylation 1799 (2,6-dihydroxy-1,1,1,7,7,7-he xafluoro-2,6-bis(trifluoromethyl)heptan-4 one[bis(he xafluoroacetonyl)]acetone) suggested that IL-3 deprivation leads to an increase in this intracellular pool of Ca2+ in 32D-NEO but not in 32D-BCL2 cells. Re-addition of IL-3 to factor-deprived 32D-NEO cells reversed the changes in thapsigargin- and 1799-releasable Ca2+ pools and rescued many of the cells from death. Measurements of total cellular Ca2+ revealed no difference in 32D-NEO cells before and after IL-3 withdrawal, suggesting that the observed alterations in mitochondrial and nonmitochondrial Ca2+ pools result from intracellular repartitioning of Ca2+. Treatment of IL-3-deprived 32D-NEO cells with Ca2+ ionophores blocked DNA fragmentation and prolonged cell survival, whereas addition of Ca2+ chelators to IL-3-stimulated 32D cells resulted in oligonucleosomal DNA fragmentation and cell death, suggesting that diminutions in the concentrations of Ca2+ in cytosol, endoplasmic reticulum, or other intracellular compartments either directly or indirectly regulate apoptosis in these lymphokine-dependent hematopoietic cells. PMID- 8454621 TI - Human recombinant interleukin-1 beta up-regulates elastin gene expression in dermal fibroblasts. Evidence for transcriptional regulation in vitro and in vivo. AB - The effects of human recombinant interleukin (IL)-1 beta on elastin gene expression were studied in human skin fibroblast cultures by Northern hybridization and transient transfection experiments. Incubation of the cells with IL-1 beta elevated the elastin mRNA steady-state levels by approximately 3- to 4-fold. A similar increase was noted at the protein level, when estimated by indirect immunofluorescence of cultured cells. This effect was independent of the on-going protein synthesis, as tested by incubation with cycloheximide. Transient transfections of the dermal fibroblasts with a human elastin promoter/chloramphenicol acetyltransferase (CAT) reporter gene construct suggested transcriptional regulation, since the CAT activity in cells incubated with IL-1 beta was similarly increased approximately 3-fold. Enhancement of the human elastin promoter activity by IL-1 beta was also noted in fibroblast cultures established from the skin and lungs of transgenic mice which have integrated the human promoter/CAT construct into their genome and express it in a tissue-specific manner. Furthermore, subcutaneous injection of IL-1 beta to the mice resulted in a approximately 4-fold elevation of the CAT activity in the skin after a 30-h incubation, as compared to the CAT activity in the skin of control animals. Collectively, these data indicate that IL-1 beta up-regulates elastin gene expression in fibroblast cultures as well as in the skin in vivo, and the activation occurs at the transcriptional level. PMID- 8454622 TI - Purification of the cellular C1 factor required for the stable recognition of the Oct-1 homeodomain by the herpes simplex virus alpha-trans-induction factor (VP16). AB - The assembly of specific multiprotein complexes on the herpes simplex virus alpha/IE (immediate early) enhancer elements requires the interactions of the Oct 1 POU homeodomain, the viral alpha TIF (alpha-trans-induction factor) (VP16), and at least one additional cellular factor, the C1 factor. The C1 factor interacts directly with alpha TIF, likely forming an intermediate protein complex that recognizes the Oct-1 homeodomain-DNA complex. The biochemical purification of the mammalian C1 factor suggests that it is composed of multiple subunits of related, but heterogeneous, polypeptides. The interaction of a subset of these polypeptides with alpha TIF is stimulated by post-translational modifications of the C1 proteins, suggesting that this factor may be a critical target for the regulation of the herpes simplex virus alpha/IE transcription. PMID- 8454623 TI - A common ATP requirement for open complex formation and transcription at promoters containing initiator or TATA elements. AB - The involvement of ATP during transcription initiation from three basic types of RNA polymerase II promoters was investigated. Hydrolysis of the beta-gamma bond of ATP was found to be required for transcription at TATA, initiator, and initiator + TATA promoters. For all three promoters, ATP is required to melt the transcription start site region during formation of a functional open transcription complex. The use of ATP to open the DNA strands occurs rapidly. The resulting open complex is transient, since the start site re-closes rapidly upon initiation. The requirements for efficient open complex formation were similar to those for transcription in that both upstream elements and a basal element, either TATA or initiator, were necessary. The results further suggest that TATA dependent and initiator-dependent preinitiation complex assembly pathways converge, prior to a step in which the strands are rapidly opened in the presence of ATP, to form analogous open complexes. PMID- 8454624 TI - The expression of saporin, a ribosome-inactivating protein from the plant Saponaria officinalis, in Escherichia coli. AB - We have isolated and sequenced genomic clones from the DNA of Saponaria officinalis using a cDNA probe that encodes proteins with high homology to saporin-6, one of the most potent of the ribosome-inactivating proteins that is currently used for the construction of immunotoxins and mitotoxins. Sequence differences in the clones suggest a multigene family of proteins. These data agree with observations of several different proteins with ribosome-inactivating protein activity and similar structure. Two of the genomic clones encode proteins that have identical sequences to two of the four isoforms of saporin-6. We have inserted the DNA from one genomic clone into an Escherichia coli expression system that encodes a signal sequence for export to the bacterial periplasmic space. Exportation is observed and the isolated gene product has ribosome inactivation activity similar to the native protein. Sequence analysis shows differential processing of the remaining plant signal sequence. The majority of the expressed protein remains intracellular and this material also shows high specific activity and differential processing. Saporin as an immunotoxin in clinical trial and as a mitotoxin in experimental models has been extremely efficacious. These data indicate the ability to produce fusion proteins with saporin and cell-binding ligands for production of new reagents for further clinical and experimental use. PMID- 8454625 TI - Proofreading and the evolution of a methyl donor function. Cyclization of methionine to S-methyl homocysteine thiolactone by Escherichia coli methionyl tRNA synthetase. AB - A cyclic sulfonium compound, S-methyl homocysteine thiolactone (SMHT), is formed from methionine during in vitro tRNA aminoacylation catalyzed by Escherichia coli methionyl-tRNA synthetase. The mechanism of SMHT formation involves enzymatic deacylation of Met-tRNA (k = 0.06 s-1) and, to a lesser extent, Met-AMP (k = 0.02 s-1). Cyclization of methionine, reminiscent of cyclization of homocysteine during editing, illustrates the limited ability of methionyl-tRNA synthetase to discriminate against the cognate methionine at the editing site designed for the noncognate homocysteine. In early stages of biotic evolution, SMHT, a sulfonium compound, may have fulfilled the present day methyl donor function of S adenosylmethionine. Existing homologies between methionyl-tRNA synthetase and S adenosylmethionine synthetase indicate evolutionary relatedness of the two proteins. PMID- 8454627 TI - CCAAT/enhancer-binding protein-related proteins bind to the unusual promoter of the aspartate aminotransferase housekeeping gene. AB - The cytosolic aspartate aminotransferase (cAspAT) gene is ubiquitously expressed but it is regulated by hormones in a tissue-specific manner. In vitro DNase I footprinting studies of a 260-base pair fragment carrying the basal promoter activity revealed that three CCAAT sequences bind liver nuclear proteins (protected regions P2, P3, P4). Competition studies, the heat resistance of these proteins, and identical footprints obtained using a recombinant CCAAT/enhancer binding protein (C/EBP) alpha fragment indicate that they belong to the C/EBP family of transcription factors. A fourth protected region P1, overlapping the P2 region, was observed in the liver in the presence of competing oligonucleotides containing the C/EBP site. In cotransfection experiments, the C/EBP beta protein trans-activated 10-15-fold the cAspAT gene promoter in HepG2 cells. Deletion studies revealed that regions P2 and P4 are critical for promoter activity. In gel retardation experiments, the P4 region bound different C/EBP-related proteins in different tissues: the brain protein is heat sensitive in contrast to the liver protein. The synthetic oligonucleotide OL 1-2, which covers the P1 and P2 regions, binds C/EBP-like proteins as well as NF1 and CP1 (or NFY) transcription factors, but the preferential binding of one of these protein is tissue-specific. In summary, using the cAspAT gene promoter, we have shown that ubiquitously active promoters may be recognized by different proteins in different tissues. PMID- 8454626 TI - Primary structure and characterization of an Arabidopsis thaliana calnexin-like protein. AB - A cDNA clone (pTE-83) encoding a protein (CNX1p) related to the microsomal Ca(2+) binding protein, calnexin, was isolated from an Arabidopsis thaliana expression library. Southern and Northern hybridization indicated that CNX1 is a single-copy gene encoding a message of 1900 nucleotides. The open reading frame encodes a polypeptide with 530 amino acids, a molecular mass of 60.5 kDa, and overall 48% identity to dog calnexin. Both animal calnexin and CNX1p contain a large luminal domain followed by a single potential membrane-spanning domain near the C terminus and a small C-terminal domain exposed to the cytoplasm. The in vitro translation product from the cloned cDNA yielded a polypeptide of 67 kDa that was co-translationally imported into dog microsomes and processed to a 64-kDa product. Antibodies generated against the C-terminal half of the protein cross react with an identically sized protein present in the microsomal fraction from Arabidopsis. Both the imported and native proteins are cleaved by trypsin to a 59 kDa product indicating that the gene product was indeed correctly processed and translocated into dog microsomes and that the membrane topology of CNX1p resembles that of dog calnexin. The presence of a calnexin-like protein within the plant kingdom indicates that this protein is widespread and involved in processes fundamental to all eukaryotes. PMID- 8454628 TI - Recombinant soluble human interleukin-5 (hIL-5) receptor molecules. Cross-linking and stoichiometry of binding to IL-5. AB - Recombinant soluble human interleukin-5 receptor alpha (shIL-5R alpha) has been expressed in COS-1 cells and in baculovirus-infected cells. The protein was purified from the supernatant by chromatography on concanavalin A-Sepharose, MonoQ, and a final gel filtration step. A chimeric fusion receptor protein (hIL 5R alpha-h gamma 3) was constructed by fusion of the cDNA corresponding to the shIL-5R alpha to the cDNA corresponding to the Fc part of the human IgG C gamma 3 chain, and was expressed in baculovirus-infected insect cells. The chimeric receptor was secreted as a disulfide-linked homodimer, and was purified by protein G affinity chromatography. In a solid-phase binding assay the shIL-5R alpha and the bivalent hIL-5R alpha-h gamma 3 were found to bind hIL-5 with a similar affinity, corresponding to the membrane-bound, low affinity hIL-5R alpha. SDS-polyacrylamide gel electrophoresis of shIL-5R alpha cross-linked to radiolabeled hIL-5, suggested that one shIL-5R alpha molecule binds to one hIL-5 homodimer molecule. Gel filtration studies of the complex formed between the shIL 5R alpha and hIL-5 pointed toward the same stoichiometry of binding. The formation of such a complex could be observed by electrophoresis in native gels. Immunoaffinity chromatography using a non-neutralizing monoclonal antibody directed against hIL-5, followed by size column chromatography, allowed the purification of the complex. The data obtained from the amino acid analysis of the constituents of the complex blotted from an SDS-polyacrylamide gel, and from the amino acid composition of the complex blotted from a native polyacrylamide gel, provided direct evidence that the shIL-5R alpha binds the hIL-5 dimer in a 1:1 ratio. PMID- 8454629 TI - Association of both enoyl coenzyme A hydratase and 3-hydroxyacyl coenzyme A epimerase with an active site in the amino-terminal domain of the multifunctional fatty acid oxidation protein from Escherichia coli. AB - An Escherichia coli mutant multienzyme complex of fatty acid oxidation, composed of two 41-kDa beta-subunits and two 79-kDa mutant alpha-subunits with the alpha/Gly116-->Phe substitution, has been overproduced and purified. The catalytic properties of 3-ketoacyl-coenzyme A (CoA) thiolase and L-3-hydroxyacyl CoA dehydrogenase were found to be virtually identical with those of the wild type, whereas both enoyl-CoA hydratase and 3-hydroxyacyl-CoA epimerase activities were eliminated by the alpha/Gly116-->Phe mutation. delta 3-cis-delta 2-trans Enoyl-CoA isomerase was only slightly affected by the mutation. The results of this study, together with the sequence analysis of the large alpha-subunit of the E. coli complex (Yang, X.-Y. H., Schulz, H., Elzinga, M., and Yang, S.-Y. (1991) Biochemistry 30, 6788-6795) and a demonstration of the epimerization of D-3 hydroxyacyl-CoAs in E. coli via a dehydration/hydration mechanism (Smeland, T. E., Cuebas, D., and Schulz, H. (1991) J. Biol. Chem. 266, 23904-23908), lead to the conclusion that enoyl-CoA hydratase and 3-hydroxyacyl-CoA epimerase are associated with a common active site in the amino-terminal domain of the multifunctional fatty acid oxidation protein. Thus the E. coli hydratase and epimerase activities represent two functions of a unique crotonase that converts both L- and D-3-hydroxyacyl-CoAs to 2-trans-enoyl-CoAs. Moreover, the results suggest that the amino-terminal domain of the large alpha-subunit is also involved in the isomerase activity but the key residue(s) required for catalyzing the isomerization is distinct from the crotonase. PMID- 8454630 TI - In vitro activation of the transcription factor ISGF3 by interferon alpha involves a membrane-associated tyrosine phosphatase and tyrosine kinase. AB - Interaction of interferon alpha (IFN alpha) with its cell surface receptor rapidly activates the formation of the transcription complex ISGF3, which subsequently translocates to the nucleus and stimulates the expression of a variety of early response genes. We have recently developed a cell-free system where IFN alpha can activate the formation of ISGF3 in vitro. This system has enabled us to demonstrate that the component of the ISGF3 transcription complex which is modified by IFN alpha treatment (ISGF3 alpha) is membrane-associated and that its activation involves a protein kinase. Using a combination of specific tyrosine kinase and phosphatase inhibitors and monoclonal anti-phosphotyrosine antibodies we now are able to demonstrate that IFN alpha-activated transcription involves at least a two-step process where a membrane-associated tyrosine phosphatase and a tyrosine kinase lead to modification of ISGF3 alpha and subsequent formation of the complete complex. Furthermore, formation of the ISGF3 complex is specifically disrupted by protein tyrosine phosphatase and can be reversibly dissociated by the phosphotyrosine analogue phenylphosphate. The latter observation suggested that SH2 and/or SH3 domains may be required for the stable formation of this transcription complex. PMID- 8454631 TI - Differential inhibition of prostaglandin endoperoxide synthase (cyclooxygenase) isozymes by aspirin and other non-steroidal anti-inflammatory drugs. AB - Murine prostaglandin endoperoxide (PGH) synthase-1 and PGH synthase-2 expressed in cos-1 cells were found to be differentially sensitive to inhibition by common nonsteroidal anti-inflammatory drugs (NSAIDs). Aspirin completely inhibited bis oxygenation of arachidonate by PGH synthase-1; in contrast, aspirin-treated PGH synthase-2 metabolized arachidonate primarily to 15-hydroxyeicosatetraenoic acid (15-HETE) instead of PGH2. ID50 values were determined for a panel of common NSAIDs by measuring instantaneous inhibition of cyclooxygenase activity using an oxygen electrode. Among common NSAIDs tested, indomethacin, sulindac sulfide, and piroxicam preferentially inhibited PGH synthase-1; ibuprofen, flurbiprofen, and meclofenamate inhibited both enzymes with comparable potencies; and 6-methoxy-2 naphthylacetic acid preferentially inhibited PGH synthase-2. These results demonstrate that the two PGH synthases are pharmacologically distinct and indicate that it may be possible to develop isozyme-specific cyclooxygenase inhibitors useful both for anti-inflammatory therapy and for delineating between the biological roles of the PGH synthase isozymes. PMID- 8454632 TI - Identification of a novel member of mouse hsp70 family. Its association with cellular mortal phenotype. AB - A novel 66-kDa protein, named p66mot-1, is identified to be associated with cellular mortality by virtue of its presence in cytosolic fractions of serially passaged mouse embryonic fibroblasts (MEF) and the mortal hybrids obtained by the fusion of mortal (MEF) and immortal (MN48-1, derivative of NIH 3T3) cells. Immortal cells lack this protein in their cytosolic fractions. cDNA cloning and homology search placed it in the heat shock protein 70 (hsp70) family. Microinjection of anti-p66 antibody to senescent MEF could transiently stimulate their cell division, which supports the cellular mortality-related function of p66mot-1. PMID- 8454633 TI - Cloning and expression of PTP-PEST. A novel, human, nontransmembrane protein tyrosine phosphatase. AB - The polymerase chain reaction was used to amplify protein tyrosine phosphatase (PTPase)-related cDNA from a template of total RNA isolated from human skeletal muscle. A novel PTPase, which we term PTP-PEST, was detected by this method. The polymerase chain reaction fragment was used to screen two different HeLa cell libraries to obtain full length cDNA clones. The cDNA predicts a protein of 510 amino acids, approximately 60 kDa, that does not contain an obvious signal sequence or transmembrane segment suggesting it is a nonreceptor type enzyme. The PTPase domain is located in the N-terminal portion of the molecule and displays approximately 35% identity to other members of this family of enzymes. The C terminal segment is rich in Pro, Glu, Asp, Ser, and Thr residues, possessing features of PEST motifs which have previously been identified in proteins with very short intracellular half-lives. The protein was expressed in Escherichia coli as a fusion product with glutathione S-transferase. Intrinsic activity was demonstrated in vitro against a variety of phosphotyrosine-containing substrates including BIRK, the autophosphorylated cytoplasmic kinase domain of the insulin receptor beta subunit. It did not dephosphorylate phosphoseryl-phosphorylase a. PTP-PEST mRNA is broadly distributed in a variety of cell lines. Stimulation of human rhabdomyosarcoma A204 cells, a transformed muscle line, with insulin led to an approximately 4-fold induction of PTP-PEST mRNA within 36 h. PMID- 8454634 TI - Mammalian transcription factor PBP. Characterization of its binding properties to the proximal sequence element of U6 genes. AB - The DNA binding properties of human transcription factor PBP, which specifically binds to the proximal sequence element of mammalian U6 genes and which plays a pivotal role during their transcription, were analyzed both qualitatively and quantitatively. As a prerequisite, we analyzed the optimal conditions for DNA binding of the PBP by assaying the stability of the interaction against increasing concentrations of salt, dithiothreitol, and heparin. The protein, which does not induce DNA bending, has a characteristic sensitivity against elevated temperatures and precipitously loses activity between 41 and 43 degrees C, a property which can be used for selective inactivation of the protein. Subjection of the PBP to limited proteinase K treatment showed that the protein consists of at least two functional domains, one of which is required for DNA binding. The PBP binds to the PSE with a much higher specific equilibrium constant (Ks = 1.33 x 10(11) M-1) than to nonspecific DNA (Kn = 1.18 x 10(5) M 1). The association and dissociation rates of PBP.PSE interactions were quantitatively determined by kinetic analyses. The pronounced lag phase during the initiation reaction of mammalian U6 transcription in vitro is probably correlated with the slow binding of the PBP to its target sequence. Once formed, however, the PBP.PSE complex is very stable and has a much lower dissociation (kd = 1.84 x 10(-5) s-1) than association rate constant (ka = 0.18 x 10(6) M-1 s-1). Collectively, the results demonstrate that the PSE binding protein stably associates with a high affinity to its cognate promoter sequence, and this process represents one of the primary events in the formation of the preinitiation complex on the U6 gene. Finally, we analyzed the effect of individual base pair mutations within mammalian U6 PSE sequences on the binding of the PBP. PMID- 8454635 TI - Purification, primary structures, and antibacterial activities of beta-defensins, a new family of antimicrobial peptides from bovine neutrophils. AB - A new family of cysteine-rich antimicrobial peptides from bovine neutrophils was isolated and characterized. Thirteen structurally homologous peptides were purified to homogeneity from a granule-rich cytoplasmic fraction of purified blood neutrophils. The complete sequences of the peptides were determined by a combination of enzymatic digestion, Edman degradation, and additional biochemical characterization of the carboxyl termini. The peptides are characterized by a highly cationic 38-42-residue chain which includes 6 invariantly spaced cysteines which form three disulfides. They share a highly conserved consensus sequence which is also found in a recently described epithelial antimicrobial peptide from bovine trachea. The in vitro antibacterial activities of the 13 neutrophil peptides, determined in assays using Staphylococcus aureus and Escherichia coli as test organisms, demonstrated that each peptide possessed antimicrobial activity, and that several were as active as the most potent neutrophil defensin, rabbit NP-1. Though the structural and functional attributes of the bovine neutrophil peptides are similar to those of defensins, the two peptide families are distinguished by their unique consensus sequences and additionally by differing tridisulfide motifs. We therefore propose that this new defensin-like antimicrobial peptide family be named beta-defensins. PMID- 8454636 TI - Characterization of the disulfide motif in BNBD-12, an antimicrobial beta defensin peptide from bovine neutrophils. AB - BNBD-12, a prototype beta-defensin peptide from bovine neutrophils, was chosen for determination of the disulfide motif in this family of tridisulfide antimicrobial peptides. Disulfide-containing fragments of BNBD-12 were generated by incubation with trypsin, and the amino acid composition of one tryptic fragment allowed for the assignment of one of the three disulfides. The remaining two disulfides, contained in a 16-residue tryptic oligopeptide, were characterized by amino acid analysis of fragments generated by a single round of Edman degradation which cleaved the Cys-Cys peptide bond present near the carboxyl terminus of BNBD-12. Cleavage of this bond produced two disulfide containing oligopeptides, the compositions of which provided unambiguous assignments of the disulfides involved. The cystine motif in BNBD-12 differs from that of classical defensins, and indicates that the beta-defensins and defensins must have differently folded chains, though they share several functional properties. PMID- 8454637 TI - Cloning, sequencing, purification, and Gq-dependent activation of phospholipase C beta 3. AB - Six mammalian phospholipase C isozymes (PLC-beta 1, PLC-beta 2, PLC-gamma 1, PLC gamma 2, PLC-delta 1, and PLC-delta 2) have been identified at both protein and DNA levels. Here, cDNAs corresponding to a previously unidentified PLC isozyme were isolated from a rat thyroid cell FRTL cDNA library. Comparison of the predicted amino acid sequence of this new PLC with other known PLC isozymes revealed a high degree of overall similarity with PLC-beta 1 and PLC-beta 2. Thus, the new PLC was named PLC-beta 3. Comparison with PLC-beta 1 and PLC-beta 2 also revealed that the deduced amino-terminal sequence of PLC-beta 3 was incomplete by 10-20 amino acids. With the use of antibodies raised against synthetic peptides corresponding to PLC-beta 3-specific amino acid sequences, we purified PLC-beta 3 from a rat brain particulate fraction. The purified enzyme exhibited an apparent molecular mass of 152 kDa on SDS-polyacrylamide gels, as compared with 150 and 140 kDa for PLC-beta 1 and PLC-beta 2, respectively. Studies of the activation of PLC-beta isozymes by three alpha subunits of Gq class G proteins, alpha q, alpha 11, and alpha 16 in the presence of guanosine 5 O-(3-thiotriphosphate) (GTP gamma S) revealed that the extent of activation decreased in the order of PLC-beta 1 > or = PLC-beta 3 >> PLC-beta 2 for all three alpha subunits, suggesting a certain degree of specificity in the interaction of Gq alpha subunits with different PLC-beta isozymes. PMID- 8454638 TI - Apical secretion of hepatitis B surface antigen from transfected Madin-Darby canine kidney cells. AB - Hepatitis B surface antigen (HBsAg), the major envelope component of human hepatitis B virus, during infection drives the assembly and basolateral secretion from hepatocytes of both virions and subviral lipoprotein particles into the bloodstream. We studied the sorting behavior of HBsAg in the heterologous epithelial Madin-Darby canine kidney cells permanently transformed with the hepatitis B virus S gene. These cells, forming tightly packed monolayers in permeable supports, secreted HBsAg apically through a mechanism not involving transcytosis. This suggests that molecular features acting as apical addressing information, seemingly unfunctional or less efficiently used by the exocytic machinery of hepatocytes, could be contained in short hydrophilic regions of HBsAg. Lipids also could play a role in this asymmetric sorting because HBsAg is known to be secreted by forming macromolecular lipoprotein complexes rather than as a soluble protein. Together with available data, our results would imply not only the existence of tissue-specific variations in handling constitutively secreted proteins but also that these variations are strikingly dependent on the kind of protein examined. On the other hand, pulse-chase experiments with tunicamycin showed that the expression of apical information in HBsAg particles does not require N-linked glycosylation, contrasting with the known gp80 Madin Darby canine kidney-endogenous apical secretory marker. This is the first experimental evidence that carbohydrate moieties in secretory proteins do not hold domain-specific sorting signals, a fact previously shown exclusively for membrane proteins. Thus, HBsAg provides a novel model system for the analysis of the molecular mechanisms of constitutive apical secretion. PMID- 8454639 TI - Affinity purification of a somatostatin receptor-G-protein complex demonstrates specificity in receptor-G-protein coupling. AB - The inhibitory neuropeptide somatostatin (SRIF) initiates many of its physiological effects by binding to membrane receptors which are coupled to pertussis toxin-sensitive G-protein(s). We have solubilized such a SRIF receptor G-protein complex and purified it using a biotinylated SRIF analog and guanine nucleotide-dependent affinity chromatography. Following [125I-Tyr11]SRIF binding to membranes from AR4-2J pancreatic acinar cells, only two detergents, dodecyl beta-D-maltoside (D beta M) and sucrose monolaureate, extracted greater than 70% of the prebound peptide in association with receptor. The D beta M-solubilized ligand-receptor complex was extremely stable: the half-time (t1/2) for dissociation was 11 days at 4 degrees C. However, guanosine 5'-3-O (thio)triphosphate (10 microM) elicited rapid dissociation of the [125I Tyr11]SRIF-receptor complex (t1/2 < 30 s), and this effect was concentration dependent (ED50 = 4.0 + 0.3 nM). [125I-Tyr11]SRIF dissociation was also stimulated by GDP (ED50 = 4.1 +/- 0.3 microM), and the potency of GDP was increased 4-fold by 30 microM AlF4-. Thus, the solubilized receptor was functionally associated with G-proteins. Cross-linking of the soluble [125I Tyr11]SRIF-receptor complex resulted in the covalent labeling of a 70-90-kDa band, the same band that was specifically labeled in membranes. Affinity purification of the SRIF receptor-G-protein complex was accomplished by prebinding a biotinylated SRIF analog, [N-biotinyl-Leu8,D-Trp22,Tyr25]SRIF28, to membranes followed by solubilization of the ligand-receptor-G-protein complex, adsorption to streptavidin-agarose, and specific elution with 100 microM GDP, 30 microM AlF4-. G-proteins were identified in the eluate by immunoblotting with specific antipeptide antisera. Using this protocol, the G-protein subunits alpha i, alpha i-3, and beta 36 were shown to be specifically associated with the AR4 2J cell SRIF receptor. Thus, we have developed a new, generally applicable, procedure for the efficient solubilization and affinity purification of a stable SRIF receptor-G-protein complex and have characterized the specific G-protein subunits associated with pancreatic SRIF receptors. PMID- 8454640 TI - Cooperative interaction between interferon (IFN) stimulus response element and kappa B sequence motifs controls IFN gamma- and lipopolysaccharide-stimulated transcription from the murine IP-10 promoter. AB - The transcriptional regulation of the murine IP-10 gene in lipopolysaccharide (LPS) or interferon gamma (IFN gamma)-treated macrophages was investigated by analysis of regions of the gene that flank the transcription start site. A series of sequence fragments were placed 5' to the chloramphenicol acetyltransferase (CAT) reporter gene and ability to mediate transcription of CAT in response to IFN gamma or LPS treatment was studied following transient transfection in the macrophage-like cell line RAW 264.7. Analysis of larger constructs identified a potential negative regulatory site for IFN gamma response in the region between nucleotide positions -2002 and -930 and a positive regulator for LPS response in the region between bases -930 and -676. A 227-base fragment spanning positions 228 to -2 was the minimal sequence able to mediate LPS- and IFN gamma-dependent transcription of CAT. Deletion of 24 bases, which included a highly conserved IFN stimulus response element (ISRE) from the -228 construct, abolished response to IFN gamma. A 33-base fragment containing the IP-10 ISRE was able to confer both IFN gamma and LPS sensitivity upon a heterologous promoter. The ability of LPS to stimulate CAT via the ISRE was apparently mediated by intermediate expression of endogenous IFN alpha/beta. Elimination of bases -204 to -102 abolished sensitivity to LPS. This region contains two kappa B binding sites. Site-directed mutagenesis of key nucleotides in the ISRE and the two kappa B sites demonstrated that optimal response to IFN gamma required both the ISRE and one of the two kappa B sites, whereas optimal response to LPS required either both kappa B sites or one kappa B site and the ISRE. IFN gamma or LPS treatment induced sequence specific binding activity for the ISRE and the two kappa B sites. These results indicate that the 230 nucleotides upstream from the transcription start site are important for transcriptional control of the IP-10 gene in response to IFN gamma and LPS. The three defined regulatory elements function in distinct fashion for each of the two stimuli; optimal response to either IFN gamma or LPS requires cooperation between at least two sites. PMID- 8454641 TI - Construction of synthetic signals for glycosyl-phosphatidylinositol anchor attachment. Analysis of amino acid sequence requirements for anchoring. AB - Many membrane proteins are anchored to the cell surface through covalent attachment to a glycosyl-phosphatidylinositol (GPI) structure. The GPI anchor is added to proteins in the endoplasmic reticulum following recognition of a signal in the COOH terminus of the protein. We show that the GPI anchoring signal can be completely recreated by the synthetic polymer Ser3-Thr8-Leu14, but not Thr11 Leu14, inserted at the COOH terminus of a protein. This is consistent with previous reports that a small amino acid such as Ser, Gly, or Ala, but not Thr, is required at the GPI attachment site. Analysis of synthetic amino acid sequences established a basic three-part signal for GPI anchoring: a cleavage/attachment domain that requires small amino acids at the first (GPI anchor attachment) and third positions but with little specificity at the middle position, a spacer domain of approximately 8-12 amino acids, and a hydrophobic domain of at least 11 amino acids. The ability to design a totally synthetic GPI anchoring signal will allow precise probing of the fine structure of this signal. PMID- 8454642 TI - Identification of human intestinal trefoil factor. Goblet cell-specific expression of a peptide targeted for apical secretion. AB - Trefoil peptides are a recently recognized group of small peptides abundantly produced at mucosal surfaces that offer the opportunity to define mechanisms of mucosal cell-specific differentiation and to illuminate new mechanisms for the preservation of mucosal integrity. We report the cDNA cloning of a 75-amino acid human trefoil factor expressed in small and large intestinal mucosas that is highly homologous to the intestinal trefoil factor, with 70% identity at the amino acid level of the predicted mature protein. This human intestinal trefoil factor is also homologous, although to a lesser extent, to trefoil peptides expressed at other sites in the gastrointestinal tract in man, exhibiting absolute conservation of the P domain motif (CX9CX9CX4CCX9WCF) that defines this family of peptides. These findings indicate a high degree of evolutionary conservation of organ/region-specific members of this peptide family. In situ hybridization of intestinal trefoil factor demonstrates a high degree of expression in mature small intestine villus and colonic epithelial goblet cells. Immunogold staining demonstrates high concentrations of intestinal trefoil factor in the rough endoplasmic reticulum and theca of goblet cells as well as throughout the mucosal surface, consistent with vectorial secretion of this factor by goblet cells onto the intestinal luminal surface. In addition, intestinal trefoil factor was also localized within columnar epithelial cells by immunogold labeling despite the absence of mRNA. These observations suggest that peptide secreted by goblet cells might be taken up from the luminal surface and transcytosed by enterocytes. Human intestinal trefoil factor expression was also detected in the HT-29N2 and HT-29H2 subclones in conjunction with the emergence of the goblet cell phenotype, but not in the CaCO2 cell line that exhibits enterocytic phenotype. In summary, these findings confirm the existence of a highly conserved family of peptides that are abundantly expressed in distinctive regions throughout the gastrointestinal tract in a highly cell-specific pattern reflecting a goblet cell differentiation pathway. They form one of the more abundant constituents of the interface between the mucosa and "outside" environment and may provide a new paradigm of regulation of the integrity of epithelial surfaces as well as a previously unrecognized dimension of goblet cell function. PMID- 8454644 TI - Defective mannosylation of glycosylphosphatidylinositol in Lec35 Chinese hamster ovary cells. AB - The Lec35 mutation (previously designated PIR) of Chinese hamster ovary cells is a recessive mutation that affects the participation of mannose-P-dolichol (MPD) in dolichol-P-P-oligosaccharide biosynthesis in vivo, even though MPD and the respective MPD-dependent mannosyltransferases are present. The Lec35 phenotype can be partially corrected by disrupting Lec35 cells and performing the transferase reactions in vitro, suggesting that the defect may be related to mislocalization of MPD. In this study, we examined the effect of the Lec35 mutation on glycosylphosphatidylinositol (GPI) lipid biosynthesis, another pathway that requires MPD. Our data indicate that the first mannosylation reaction of GPI lipid biosynthesis is defective in Lec35 cells, with the accumulation of glucosaminylphosphatidylinositol having a fatty acyl group on inositol and a base-resistant alkyl group attached to glycerol. The same intermediate accumulates in Lec15 (MPD synthase-defective) cells. The defective mannosylation reaction of Lec35 cells was corrected in vitro and shown to require MPD. These results demonstrate that the Lec35 gene governs a general aspect of MPD metabolism affecting both GPI lipid and dolichol-P-P-oligosaccharide biosynthesis. To provide additional insight into the role of the Lec35 gene, we give evidence for an inefficient pool of MPD in Lec35 membranes. PMID- 8454643 TI - Mutagenesis of conserved residues in the phosphorylation domain of the yeast plasma membrane H(+)-ATPase. Effects on structure and function. AB - A diagnostic feature of P-ATPases is a phosphorylation motif (DKTGTLT), located in the hydrophilic center of the polypeptide chain, within which the beta aspartyl-phosphate reaction intermediate is formed. The roles of four invariant residues (Lys379, Thr380, Thr382, and Thr384) in this region of the yeast plasma membrane H(+)-ATPase have been analyzed by site-directed mutagenesis. In addition, a set of six insertion mutants was generated containing a single glycine residue at each of the indicated sites: [sequence: see text] C S D K T GT LT to examine spatial arrangements within this highly conserved domain. In order to minimize toxic effects of the mutations on cell growth, the defective ATPases were expressed behind an inducible heat shock promoter and targeted to an intracellular pool of secretory vesicles, while wild-type ATPase was maintained in the plasma membrane where it is required for viability. Secretory vesicles containing mutant ATPase were isolated as described previously (Nakamoto, R. K., Rao, R., and Slayman, C. W. (1991) J. Biol. Chem. 266, 7940-7949) and assayed for the amount of ATPase polypeptide and for rates of ATP hydrolysis and H+ pumping. All of the insertion mutations led to biosynthetic arrest of the defective enzyme, with no ATPase appearing in the secretory vesicles. Nonconservative amino acid substitutions (Lys-->Gln, Thr-->Ala) inactivated the ATPase, whereas conservative substitutions (Lys-->Arg, Thr-->Ser) retained partial activity which has been characterized in detail. There was little or no change in the Km for ATP or the pH optimum in any of the mutant enzymes. Strikingly, however, all displayed an increase in resistance to vanadate, consistent with the idea that the residues in question contribute to a phosphate/vanadate binding site or that they affect the equilibrium between E1 and E2 conformations of the enzyme. PMID- 8454645 TI - Gene inactivation in Lec35.1 (mannosylation-defective) Chinese hamster ovary cells. A cautionary note. AB - In Lec35.1 CHO mutants, mannose-P-dolichol is synthesized but does not participate in the production of glycosylphosphatidylinositol (GPI) anchor precursors or dolichol-linked oligosaccharides. We tested Lec35.1 cells for stable expression of a cDNA encoding GPI-anchored human folate-binding protein (FBP) with the eukaryotic expression vector pJB20. All normal transfectants, but no Lec35.1 transfectants, expressed FBP activity. However, rather than an inability to produce GPI anchors, lack of FBP expression in Lec35.1 was caused by gradual inactivation of the FBP cDNA. FBP cDNA became fully inactive after 2-3 months of culture, and FBP activity was not restored upon correction of the Lec35 mutation. Southern blot analysis revealed that inactivation was associated with gross rearrangement of FBP cDNA. The cellular FBP gene remained intact. Because the Lec35.1 cell line has the ability to inactivate transfected human FBP cDNA, caution should be exercised when expressing transfected cDNAs in Lec35.1 and similar GPI anchor/glycosylation mutants. Interestingly, these results suggest similarities between the Lec35.1 defect and the human disease paroxysmal nocturnal hemoglobinuria, which may involve gradual inactivation of a gene necessary for mannosylation of GPI anchor precursors. PMID- 8454646 TI - UV irradiation-induced interleukin-1 and basic fibroblast growth factor synthesis and release mediate part of the UV response. AB - UV irradiated cells release into the culture medium factors that induce, when given to nonirradiated cells, the transcription of several UV-inducible genes (collagenase I, human immunodeficiency virus type 1, metallothionein IIA). We identify here the active factors released from UV-treated HeLa cells, as interleukin 1 alpha and basic fibroblast growth factor. UV irradiation leads to increased mRNA levels for both factors and to their enhanced synthesis. Experiments with the drug suramin, which inhibits growth factor-growth factor receptor interactions and with antibodies directed against interleukin 1 alpha and basic fibroblast growth factor, suggest that growth factors do not only transduce the UV-induced signal to nonirradiated cells but act on the producer cell thus establishing an obligatory growth factor loop for at least part of the UV response. PMID- 8454647 TI - Glucocorticoid regulation of thymidine kinase (Tk-1) expression in L929 cells. AB - Glucocorticoids regulate the proliferation of mouse L cells. Incorporation of [3H]thymidine is inhibited by 70-90% within 24 h after addition of 0.1 microM dexamethasone. This effect on L cells is completely reversible. The expression of the thymidine kinase gene (Tk-1) has been examined in L cells that have been treated with 0.1 microM dexamethasone for 24 h. Dexamethasone inhibits thymidine kinase activity 70-90% after 24 h. This is associated with a 90-95% decrease in Tk mRNA abundance. The decrease in Tk mRNA is not caused by a decrease in transcription of Tk-1, as shown by nuclear run-on transcription assays. Transient expression of the CAT (chloramphenicol acetyltransferase) gene, driven by the Tk 1 promoter, was not affected by dexamethasone, and transcription of stably integrated Tk minigenes in LMTk- cells was not affected by dexamethasone. This effect was observed regardless of whether Tk cDNA was fused to the simian virus 40 promoter or the mouse Tk-1 promoter region. Conversely, expression of thymidine kinase was inhibited when stable Tk+ transformants of LMTk- cells were exposed to glucocorticoids; and inhibition of expression was observed irrespective of the promoter that was used to drive transcription of the Tk minigenes. These data indicate that glucocorticoid regulation of Tk-1 in mouse L cells is, within the limits of detection of the assays used in these studies, entirely due to a posttranscriptional mechanism. PMID- 8454648 TI - Striated muscle-type tropomyosin in a chordate smooth muscle, ascidian body-wall muscle. AB - Body-wall muscle tropomyosin (Tm) of a marine chordate, the ascidian Ciona intestinalis, was studied by protein and cDNA clone analyses. Our results indicate that body-wall muscle of Ciona contains one major Tm isoform encoded by a single gene. Unexpectedly, the sequence of this Tm resembles vertebrate striated muscle Tm isoforms, rather than those of smooth muscle or nonmuscle tissues, despite the fact that body-wall muscle is a nonsarcomeric (i.e. smooth) muscle. We also found that an apparently identical Tm isoform, derived from the same gene, is expressed at high levels in Ciona heart, a striated muscle. This is the first example of an organism in which a single Tm isoform is prominently expressed in both sarcomeric and non-sarcomeric tissues. Our results demonstrate that the characteristic features of "sarcomeric" Tm isoforms are not primarily related to sarcomeric ultrastructure per se. Instead, because ascidian body-wall muscle, unlike vertebrate smooth muscle, contains troponin, we suggest that it is the interaction with troponin that generates the selective pressure to maintain the characteristic C-terminal structure of so-called sarcomeric Tm isoforms. Our results further document the remarkable molecular similarity between the nonsarcomeric ascidian body-wall muscle and vertebrate-striated muscle. We suggest that these muscle types represent sarcomeric and nonsarcomeric variants of a fundamental class of troponin/Tm-regulated muscles, contrary to the traditional smooth/striated classification of muscle types. The possible relationship of this class of muscle to vertebrate smooth muscle is discussed. PMID- 8454649 TI - Effects of mutations that alter the Glu264-Lys387 salt bridge on the secretion of alpha-1-proteinase inhibitor. AB - The possibility that low circulating levels of alpha-1-proteinase inhibitor (A1Pi) in individuals homozygous for the S variant result from disruption of a salt bridge between Glu264 and Lys387 was examined. Mutations effecting this salt bridge were constructed by either altering the common M variant cDNA so that Glu264 was replaced by Val to produce the S variant (A1PiV264) or Lys387 was replaced by Arg (A1PiR387), Asn (A1PiN387), Glu (A1PiE387), Gly (A1PiG387), Ile (A1PiI387), or Leu (A1PiL387). Measurements of secretion from transiently transfected COS cells showed that A1PiG387 and A1PiI387 are secreted as well as and at least as rapidly as A1PiM; the S variant and A1PiL387 are secreted to about the same extent as, but somewhat more slowly, than A1PiM; and the variants containing polar or charged residues at position 387 are poorly secreted, and unlike the other variants in this series undergo significant degradation by 2 h of chase. We conclude that the low circulating level of A1PiS is not due to inefficient secretion nor to excessive intracellular degradation of this variant. In addition we suspect that the lack of secretion of variants with Lys387 replaced by other charged or polar residues is due to alteration of a highly conserved sequence near the carboxyl terminus of A1Pi. PMID- 8454650 TI - Functional elements DE2A, DE2B, and DE1A and the TATA box are required for activity of the chicken alpha A-crystallin gene in transfected lens epithelial cells. AB - alpha A-crystallin is an abundant soluble protein of the vertebrate eye lens. In addition to the TATA box, four positive cis-regulatory elements of the chicken alpha A-crystallin gene have been identified by linker scanning mutagenesis, DNase I footprinting, and gel mobility shift experiments. The regulatory elements described here have been named DE2A (at positions -144 to -134), DE2B (at positions -128 to -118), and DE1A (at positions -114 to -103). DE2A and DE2B form a dyad of symmetry between positions -141 and -118 (5'-AGACTGTCAT....AGGTCAGTCT 3'), consistent with the close similarity in the mobility of complexes formed with lens nuclear proteins by these two elements. Mutations in DE2A, DE2B, and DE1A leading to loss of promoter activity using the bacterial chloramphenicol acetyltransferase reporter gene transfected into primary embryonic chicken lens epithelial cells resulted in a corresponding loss in the ability to compete for complex formation with lens nuclear proteins in gel mobility shift assays. Mutation of the alpha A-CRYBP1-like site (-67/-57), necessary for function of the mouse alpha A-crystallin promoter, did not affect the activity of the chicken promoter. The DNase I footprinting and gel mobility shift experiments confirmed the previously noted binding of nuclear proteins to a dyad of symmetry at positions -153 to -140. In contrast to DE2A, DE2B, and DE1A, mutagenesis and gel mobility shift experiments failed to correlate function and protein binding for the -153/-140 dyad. DE2A, DE2B, and DE1A agree well with the regulatory elements alpha CE1 (-162/-134), alpha CE3 (-135/-121), and alpha CE2 (-119/-99) (Matsuo, I., and Yasuda, K. (1992) Nucleic Acids Res. 20, 3701-3712) for this gene. The present results suggest, however, that the lens enhancer activity of alpha CE1 is due to the sequence -141/-134, which forms the upper half of the DE2A/DE2B dyad of symmetry, rather than the -153/-140 dyad as previously suspected. PMID- 8454651 TI - O-linked glycosylation modifies the association of apolipoprotein A-II to high density lipoproteins. AB - O-linked glycosylation is a common post-translational modification of apolipoproteins, but no structural or functional role for it has been identified. We examined the biosynthesis of apolipoprotein (apo) A-II in Hep G2 cells and in glycosylation-defective Chinese hamster ovary (CHO) cell mutants transfected with apoA-II cDNA. Three monomeric isoforms of apoA-II with an apparent molecular mass of 8.5, 9.8, and 11.4 kDa were synthesized by Hep G2 cells and transfected wild type CHO cells. The 9.8- and 11.4-kDa isoforms were sialylated but not the 8.5 kDa isoform. Transfected 1dlD cells, which are defective in the biosynthesis of galactose and N-acetylgalactosamine, only produced the 8.5-kDa isoform; however, when grown in media supplemented with these sugars, ldlD cells produced all three isoforms of apoA-II. Pulse-chase analysis of ldlD cells showed that glycosylation was not necessary for secretion of apoA-II. Glycosylation did modify the association of apoA-II with nascent high density lipoprotein (HDL) secreted by Hep G2 cells. The sialylated isoforms were lipid-poor and were present in the lipoprotein-deficient density range, whereas the nonsialylated 8.5-kDa isoform was associated with LpA-I, A-II lipoprotein particles in the HDL density range. ApoA-II from transfected ldlD cells, regardless of glycosylation, were lipid poor. When preincubated with HDL from serum, however, sialylated apoA-II from both ldlD cells and Hep G2 cells associated with lipoprotein particles within the HDL3 density, whereas nonsialylated apoA-II was found throughout the HDL density range. In summary, O-linked glycosylation is not necessary for the secretion of apoA-II but does modify the association of apoA-II to HDL and may, therefore, play an important role in the metabolism of HDL. PMID- 8454652 TI - Two-step binding mechanism of fibrinogen to alpha IIb beta 3 integrin reconstituted into planar lipid bilayers. AB - The platelet integrin alpha IIb beta 3 binds to fibrinogen and thus mediates platelet aggregation after stimulation. This integrin was isolated from human platelets and reconstituted into lipid vesicles. As judged by electron microscopy the integrin incorporated adequately only into 1,2-dimyristoylglycero-3 phosphocholine/1,2-dimyristoylphosphatidy lglycerol vesicles after removal of the detergent by adsorption to Bio-Beads. These vesicles were then used to generate planar lipid bilayers. The binding of fluorochrome labeled fibrinogen or the peptide ligand Gly-Arg-Gly-Asp-Ser-Pro-Cys (GRGDSPC) was monitored by total internal reflection fluorescence microscopy and a solid phase binding assay. Analysis of the kinetics revealed fast reversible formation of a fibrinogen/integrin precomplex (KD = 50 nM) followed by formation of a stable irreversible complex. This transition was monitored by measuring the fraction of precomplex which could be dissociated by addition of excess Gly-Arg-Gly-Asp-Ser (GRGDS). For the peptide, the KD was 1200 nM, and the rates of association and dissociation were faster than the time resolution of the method. Similar KD values were found by inhibition of fibrinogen binding to alpha IIb beta 3 in the immobilized receptor assay. Since the binding of fibrinogen was irreversible, KD values were dependent on the time period between fibrinogen incubation and peptide addition. These and results by other authors point to the biological importance of the biphasic binding process of fibrinogen to its receptor on platelets. PMID- 8454653 TI - Isolation and characterization of C-reactive protein (CRP) cDNA and genomic DNA from Xenopus laevis. A species representing an intermediate stage in CRP evolution. AB - C-reactive protein (CRP) is a prototypic acute phase protein in human and rabbit. Although it is structurally and functionally conserved from invertebrate to human, there are species-specific differences in patterns of expression and putative function. To further investigate the biological significance, regulation, and evolution of CRP, we isolated Xenopus CRP and subsequently derived and sequenced corresponding cDNA and the genomic clones. The structure and expression of Xenopus CRP were also compared to those of the other CRPs. Analyses of the amino acid sequence and the nucleotide sequence reveal that the mature Xenopus CRP is a 222-amino acid protein preceded by a 16-residue signal peptide. During development, Xenopus CRP is expressed, only when the liver appears, and therefore is not likely to play a role in early embryonic development. Compared to other species, Xenopus CRP is present at an intermediate low level of < 1 microgram/ml in the normal serum. Unlike human and rabbit CRP, Xenopus CRP is not induced by turpentine or heatshock treatment. The heatshock consensus sequence (Woo, P., Korenberg, J. R., and Whitehead, A. S. (1985) J. Biol. Chem. 265, 4136-4142) are not present in the Xenopus CRP gene. It is suggested that Xenopus CRP represents a transitional period in CRP evolution when host defenses switched from primitive innate immunity to a much more complex immune system. The constitutive functions of CRP gradually became less essential as the result of the development of a complex immune system. PMID- 8454654 TI - Phosphorylation of synaptotagmin I by casein kinase II. AB - Synaptotagmin I is an abundant synaptic vesicle protein that binds Ca2+ in a phospholipid-dependent manner and is thought to function in synaptic vesicle exocytosis. We have now studied the phosphorylation of synaptotagmin I. Synaptotagmin I is one of the major substrates in brain for casein kinase II, which phosphorylates synaptotagmin at a single threonine. The phosphorylation site was mapped using recombinant proteins to threonine 128 of synaptotagmin I, which is located in the sequence between the transmembrane region and the C2 domain repeats of synaptotagmin I. The phosphorylation site of synaptotagmin I is also present in synaptotagmin II and is evolutionarily conserved between different species. Preceding the phosphorylation site, synaptotagmins I and II contain a lysine-rich sequence. Casein kinase II phosphorylation of many substrates is strongly stimulated by the addition of polylysine, but phosphorylation of synaptotagmin I by casein kinase II is not. In recombinant proteins, removal of the lysine-rich sequence of synaptotagmin I makes its phosphorylation dependent on exogenous polylysine, suggesting that the lysine rich sequence in synaptotagmin serves as an endogenous polylysine stimulation signal for casein kinase II. Our data demonstrate that synaptotagmin I is an efficient substrate for casein kinase II at a conserved site with a possible modulatory role in nerve terminal function. PMID- 8454655 TI - Reducing pediatric burn pain with parent participation. AB - We describe and evaluate the development and implementation of a parent participation program in the burn unit at The Hospital for Sick Children, Toronto, Ontario. The effect of parent participation on the multidisciplinary team member's role had to be taken into consideration, and effective, consistent education of the support for the multidisciplinary team had to be provided to ensure the success of the program. Unit-specific minimum standards of burn care were established as guides to support team members when they established the ground rules for the parents' participation. Education sessions were also held for staff to role-play problem-solving techniques. Including parents in the difficult daily treatments required changes in our admission procedures to maintain the family unit and to assess the parents' ability to provide emotional support for their child during the procedure. Early results of the program suggested that parental participation plays a major role in reducing a child's experience of pain during invasive procedures while allowing the family relationship to continue throughout all aspects of the hospitalization. The program also improved parents' coping strategies. The parents had a better understanding of the healing process and the need for specific measures, such as the use of compression garments, during the rehabilitation phase. This understanding may improve long-term compliance with treatment. Perceived difficulties with increased parental involvement were minimized through adequate education and preparation of the staff. Continued work is required, however, to objectively evaluate parent participation and its role in effectively reducing pain in the pediatric burn population. PMID- 8454656 TI - Caloric requirements of patients with burns under one year of age. AB - Formulas for estimating the caloric requirements of pediatric patients with burns have been suggested. However, the needs of infant patients with burns have not been specifically addressed. This study was undertaken to determine the caloric intake required to maintain weight in patients under 1 year of age who had burns covering more than 25% total body surface area. Thirty patients were studied, and a comparison was made between the actual intake required for weight maintenance and the suggested calorie levels provided by published pediatric caloric formulas. The results indicated that a new formula was needed. Multivariate regression analysis indicated that body surface area and burn surface area were significant predictors of caloric requirements, but body surface area was the more important predictor in this infant population. The equation resulting from the regression provides 2100 kcal/m2 body surface area/day plus 1000 kcal/m2 body surface area burned/day. PMID- 8454657 TI - Infant monitoring resulting in burns-tissue damage: literature review and case report. AB - Noninvasive infant monitoring occasionally results in burns and tissue damage. The medical literature now contains 14 isolated reports that were summarized for this review. All 14 victims were less than 24 months of age, and of these 14, two died by electrocution. Burns and tissue damage resulted from infant respiratory monitors (six), pulse oximeters (four), electrocardiographic monitors (two), an anal myoneural junction monitor (one), and a fetal scalp monitor (one). Infant extremities were injured most often (40%), and the trunk was burned somewhat less frequently (23%). Infants were burned in the hospital (57%) only slightly more often than at home (43%). Household burns involved only infant cardiorespiratory monitors. The most common mechanism of injury was the misapplication or improper connection of electrode lead wires (57%). A full one third of infants with burns required a reconstructive surgical procedure, usually a skin graft. Risk factors related to monitor-induced burns and tissue damage have been identified and presented. Injury prevention principles are also outlined. PMID- 8454658 TI - Does inhalation injury limit exercise endurance in children convalescing from thermal injury? AB - The cardiopulmonary performance levels in children who are convalescing from thermal injury are unknown. This investigation was designed to evaluate cardiopulmonary function in children with and without inhalation injury. Forty children with a mean time since burn injury of 2.6 +/- 1.9 years and a mean burn size of 44% +/- 22% total body surface area were selected for the study and divided into two groups: inhalation injury (group 1) and non-inhalation injury (group 2). Pulmonary function studies and cardiopulmonary stress testing were completed on all patients. Both groups reached the same endurance level on the treadmill; however, patients in group 1 did so with an increased expired volume, respiratory rate, and ratio of dead space ventilation to total ventilation which indicated that there were greater demands on the respiratory system. Spirometry and lung volumes at rest showed that 64% of patients in group 1 had abnormal lung function compared with only 27% of patients in group 2. PMID- 8454659 TI - Outcome and socioeconomic aspects of suspected child abuse scald burns. AB - Fifty-two children suffering from abuse-related scald burns were admitted between January 1, 1986, and June 30, 1991. Their clinical and socioeconomic aspects were compared with those of 50 nonabused scalded children. Patients were matched for age, total body surface area burn, and percentage of full-thickness burn. Patient characteristics and initial nutritional parameters were similar except for race; a higher percentage of black children were in the abused group. A significantly longer length of hospital stay was found in the abused children after using analyses of covariance to control for percentages of total and full-thickness body surface area burn. The number of operations and frequency of complications were increased in the abused group, but not significantly so. Several significant differences were found in the socioeconomic characteristics of the two groups. Children suspected of being scalded intentionally were more likely to be part of a broken home, belong to a single parent, and have a younger mother than were children in the control group. The majority of the parents of abused children were unemployed, and all but two earned less than $20,000/year. All but one of the abused children were discharged with a person other than their parents, and compliance with rehabilitation follow-up was significantly worse than with the control group. The person suspected of performing the abuse was always a family member, except in cases where the baby-sitter was the suspected abuser. Child abuse hurts not only the child but also society by increasing the need for resources to pay for extended hospital admissions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454660 TI - Burns in children--a continued challenge. PMID- 8454661 TI - Comparison of back versus thigh donor sites in pediatric patients with burns. AB - To substantiate an observation that donor sites that are harvested from the back scar less than those that are harvested from thighs, donor sites from both areas were evaluated for the extent of scarring. For donor sites that were harvested more that 1 year before evaluation, no significant improvements were observed. Back donor sites that were evaluated less than or equal to 1 year after harvest had significant improvements in height, color, edema, suppleness, and cosmetic appearance than those harvested from thighs. Thirty-two patients had both back and thigh donor sites harvested at the same time. Back donor sites had significant improvement in scar height, color, and edema. Cosmetic improvements were also observed. Significantly more patients preferred the back donor site over that of the thigh. The back is the preferred donor site for skin grafts in the pediatric burn population. PMID- 8454662 TI - The use of Biobrane for coverage of the pediatric donor site. AB - Donor site dressings are highly diverse. The ultimate goal of any coverage is to minimize pain and healing time. Recently, synthetic laminates have become popular. Experience with Biobrane has mainly been with adult patients. This study examines the use of Biobrane in a pediatric population. One hundred eight consecutive applications of Biobrane in 95 patients (mean age 7.9 years) were reviewed. All applications were treated in identical fashion. Biobrane was left in place until healing occurred unless primary nonadherence occurred or fluid collections developed over a significant area, rendering the area nonadherent. Forty-three early removals of Biobrane were necessary at a mean of 3 1/2 days after application. The back and hip regions, with 43% and 80% early removal rates, respectively, were the areas where Biobrane was least successful in providing donor coverage until the site healed. The chest and thigh had successful full-term coverage in greater than 90% of cases. The principal basis for early removal was fluid accumulation, which reduced adherence. Early removal did not affect the healing time of the donor site. These results demonstrate a modest effectiveness of Biobrane as a donor site dressing on the back and hip regions in pediatric patients with burns. Selection of sites for which good success can be expected should be paramount in the decision to use this donor site material in this patient population. PMID- 8454663 TI - A comparison of full-thickness versus split-thickness autografts for the coverage of deep palm burns in the very young pediatric patient. AB - From 1984 through 1989, 24 patients with 30 acute palmar burns (six were bilateral) that required skin grafting were evaluated to compare the efficacy of split-thickness versus full-thickness autografting. Sixteen of the palms had split-thickness skin grafts and 14 had full-thickness skin grafts. Normal range of motion was found in 8 of 14 palms that were treated with full-thickness skin grafts and in 4 of 16 for those that were treated with split-thickness skin grafts. Significantly fewer reconstructive surgical procedures were required in the palm burns that were treated with full-thickness skin grafts (full-thickness = 3 of 14 and split-thickness = 10 of 16). The results demonstrate improved function and decreased need for reconstructive procedures when full-thickness skin grafts are used for the treatment of deep palm burns in young pediatric patients. PMID- 8454664 TI - Management of the pediatric patient with burns. AB - Two million people in the United States receive medical treatment each year for burn injuries. One hundred thousand of these patients are hospitalized, and 7800 die as a direct result of their injuries. Of the patients that are hospitalized 30% to 40% are under 15 years of age. Sixty-seven percent are male. The average age of children with burns is 32 months. Flame burns account for approximately 13% of accidents, scalds account for 85%, and electrical and chemical burns account for approximately 2%. The majority of scald injuries are small. Sixteen percent of burn injuries are not accidental, and approximately half of these are a result of documentable, inflicted abuse. PMID- 8454665 TI - The early release of axillary contractures in pediatric patients with burns. AB - In spite of the common teaching that contracture releases should be avoided until scars have matured, the Cincinnati Shriners Burns Institute has been releasing contractures in immature scars to prevent prolonged loss of range of motion. To evaluate the efficacy of axillary releases and, especially, to determine whether releases performed in immature scars were detrimental, axillary releases that were performed between January 1, 1988 and December 31, 1989 were evaluated for improvements in abduction and flexion. Overall, axillary releases significantly improved abduction and flexion, and the improvement was maintained for at least 1 year. Comparison of early (less than 1 year after burn injury) with late (more than 1 year after burn injury) releases revealed that the preoperative limitation was worse in the early release group but that the ultimate outcomes were similar. Waiting for scars to mature before performance of contracture releases is not necessary. PMID- 8454666 TI - Tissue expansion in pediatric burn reconstruction. AB - Tissue expansion has gained increased acceptance in postburn reconstruction. In this study, the clinical outcomes for 17 pediatric patients with burns are outlined. A total of 46 tissue expanders were inserted for the reconstruction of postburn scalp alopecia and burn scars. The average size of the soft-tissue defect was 124 cm2, and the mean time to follow-up was 19 months. Overall outcome in most cases was excellent; however, complications were common (37%) and included infection, exposure, port loss, and partial flap necrosis. Five patients in the scalp reconstruction group required transfusions (45%). Tissue expansion in pediatric burn reconstruction is a useful technique, which may yield superb results; however, careful surgical planning is essential to avoid complications. PMID- 8454667 TI - The relative risk of tissue expansion in the pediatric patient with burns. AB - Tissue expansion has been successfully used for reconstruction after burn injury. The purpose of this study was to investigate the relative risk of complications of tissue expansion in the pediatric population. Children with burns who underwent reconstruction with tissue expansion were studied (37 expanders in 14 patients). Patients without burns who were also treated with tissue expansion served as a comparative group. The patients without burns included children with congenital anomalies (70 expanders in 37 patients) and acquired problems (40 expanders in 25 patients). Complications occurred in 10.8% of the expanders in the burn group, in 11.2% of the expanders in the congenital anomalies group, and in 7.5% of the expanders in the acquired problems group. No significant difference between the groups was noted. We conclude, therefore, that the child with burns is at no greater risk of complications from tissue expansion than are other children. PMID- 8454668 TI - Development of septic arthritis by hematogenous seeding in a pediatric patient with burns. AB - We describe a pediatric patient with burns who experienced a septic hip joint from hematogenous seeding by sustained Staphylococcus aureus bacteremia. A search for a central vascular focus of the bacteremia included the use of an indium scan, which localized purulence within the left hip joint. The physical findings, radiographic findings, and subsequent aspiration of the hip joint were diagnostic for a septic arthritis. This case alerts the physician that the pediatric hip is a potential site for infection in the presence of bacteremia. Once infected, the joint may become a secondary source of an ongoing bacteremia. The diagnostic work up and treatment for a septic hip have been discussed. This occult site of infection is easy to overlook because a painful hip joint in the pediatric patient with burns may be confused for painful burn wounds. The prerequisites to joint infections in this population were all present: bacteremia, intercurrent illness, unique vascular anatomy, and an impaired immune response. PMID- 8454669 TI - This one's for Billy. PMID- 8454670 TI - Social competence and behavioral problems of pediatric survivors of burns. AB - Sixty children (35 boys, 25 girls) with burns were surveyed at least 1 year after burn injury to assess the behavior problems and difficulties with competency that they were having. The Child Behavior Checklist, the Youth Self Report, and the Teacher Report Form developed by Achenbach were administered to obtain standardized measures of behavior and competence. The mean values for these scales were in the normal range for each age and sex. However, the Child Behavior Checklist revealed a statistically significant (p < 0.05) increase in problems and decrease in competency for most age groups and both sexes when compared with the reference population. In contrast, the Teacher Report Form and the Youth Self Report revealed very few differences from the reference population. The burn size (15% to 20% total body surface area, 35% to 50% total body surface area, and > 70% total body surface area) did not account for any of the group differences. Further studies involving detailed clinical interviews and other standardized measures are needed to understand the discrepancies between the Child Behavior Checklist and the other scales. PMID- 8454671 TI - Parental stress as a cause and effect of pediatric burn injury. AB - The current study reports assessments of stress for parents of children with acute burns at the time of hospital admission and during the first 5 years after injury. At each assessment, parents of children with burns report neither more nor less stress than a normal population. At the time of admission, parents of children with acute burns do not differ from the normal sample on any of the measures of parenting stress. Parents of recovering children with burns do report significant changes. They report significantly higher depressive symptoms at year 2 after the child's burn injury and lower than normal levels of depression in years 4 and 5 after the child's injury. During the recovery period, these parents also attribute their stress more often to the child with burns, whereas other parents more evenly divide blame among their children and their personal characteristics. PMID- 8454672 TI - Psychologic adjustment after childhood burn injuries as predicted by personality traits. AB - The purpose of this study was to examine the nature of psychologic adjustment in persons who have survived childhood burn injuries. It was hypothesized that survivors who were well-adjusted psychologically would possess specific personality traits that would differentiate them from their poorly adjusted peers. Thirty-two subjects were given a standardized assessment of psychologic adjustment and a standardized personality inventory. The subjects were assigned to either a "poorly adjusted" group or a "well-adjusted" group, on the basis of each subject's score on a standardized measure of adjustment. There were no significant differences between the two groups in variables of gender, age, time since burn, or age at time of burn injury. The results indicate three personality traits that seem to be related to psychologic adjustment after a severe burn injury in pediatric patients. PMID- 8454673 TI - Sleep disorders in children after burn injury. AB - Eighty-two children and adolescents between the ages of 30 months and 20 years (mean, 11.8 years) who were admitted to one of two pediatric burn units with a mean initial burn injury of 43.8% total body surface area and a mean age at time of injury of 4.2 years were studied 1 year or more after burn injury (mean, 7.3 years). Subjects were found to have profound at-home sleep disorders, which were manifested as nightmares in 30 subjects (37%), bed-wetting in 20 (24%), and sleep walking in 6 (18%). Dream content related to normal childhood topics in 45 patients (55%), burn injury in 6 (7%), and burn treatment in 5 (6%). No relationship exists between age at time of burn, length of time after burn injury, cause of burn injury, family history of nightmares, or patient history of bed-wetting and the incidence of nightmares. Daytime naps were reported in 50 subjects (63%), although 46 (mean age, 11.7 years) were well beyond the normal age for napping. PMID- 8454674 TI - Absence of postburn hypermetabolism in a group of children with serious burns. AB - Hypermetabolism proportional to wound size is the expected response in patients who sustain large burns. This metabolic response persists until wound closure is achieved. The value of this response to the injured host remains unproven. Between 1978 and 1991, 104 patients with burns covering 30% or more of the body surface area underwent partitional calorimetry as a component of various research protocols. Thirteen of these patients failed to demonstrate an increase in metabolic rate as compared with a control group. These patients without hypermetabolism were compared with case-matched patients who demonstrated the expected increase in metabolic rate. Although they were not hypermetabolic in response to the burn injury, five of these patients were exposed to a cold stress and were able to increase their metabolic rate appropriately. The failure to mount a hypermetabolic response did not impact the clinical course as measured by survival, length of hospital stay, or maximum weight loss. PMID- 8454675 TI - Americans With Disabilities Act. AB - The Americans with Disabilities Act gives all Americans with disabilities a chance to achieve the same quality of life that individuals without disabilities enjoy. This act prohibits discrimination on the basis of disabilities in employment, public services, privately operated public accommodations, services, and telecommunications. The Americans with Disabilities Act is divided into five titles. Title I of the act pertains to discrimination against the disabled in the workplace. Title II prevents discrimination against persons with a disability in state and local government services. Title III prohibits discrimination against persons with disabilities in places of public accommodations and commercial facilities. Title IV ensures that companies offering telephone services to the general public provide special services for individuals with hearing and speech impairments. Under the enforcement provisions of the Americans with Disabilities Act, stringent penalties will be implemented for failure to comply with its provisions. PMID- 8454676 TI - Longitudinal hand grip and pinch strength recovery in the child with burns. AB - Hand strength of seven patients was evaluated prospectively. A range-of-motion exercise program, compression therapy, and splinting schedules were provided. Fine prehension; lateral, tip-to-tip, and tripod pinch were measured by pinch meter. Grip strength was measured by dynamometer. Comparisons were made between test strengths and published norms for age and sex with analysis of variance. Significance was accepted at p < 0.05. At discharge, all four strength measurements were significantly less than normal for age and sex. Grip and tripod strengths were improved by 6 weeks. All measurements were improved at 6 months after discharge, although grip and lateral pinch remained significantly less than norms. In conclusion, the measurements of tip-to-tip and tripod pinch at 6 months may not signify limitations in performance of activities of daily living. In spite of significantly lower than normal grip and lateral strength measurements at 6 months, it cannot be determined whether this hinders performance of daily living skills. PMID- 8454677 TI - An appearance-function shift in children's object naming. AB - The relative importance of appearance and potential function in children's object naming was examined. Potential function is an object capability that may not be currently realized (e.g. an empty mug has the potential to hold coffee). In Study 1, sixteen children from each of three age groups (3;8, 4;8, and 6;1) were taught novel names for unfamiliar objects; they then had to decide whether these applied to items that resembled the training objects in either appearance or potential function. The youngsters were also shown deceptive objects (e.g., an eraser that looked like a pencil) and had to choose between familiar appearance and function names for them (e.g., pencil or eraser). The frequency of function-based responding in both tasks increased with age. In Study 2, the name training procedure was revised so that equal emphasis was given to both apparent and functional features. The main results of the first study were replicated. Neither study obtained evidence of a strong relation between the appearance-function shift and increased understanding of the appearance-reality distinction. PMID- 8454678 TI - The functions of novel word compounds. AB - The traditional assumptions that novel word compounds fill lexical gaps and allow speakers to convey an intended meaning more precisely were explored. Examples from spontaneous language demonstrated that some novel compounds occur in the absence of a lexical gap and that not all compounds serve a communicative function. The relation between communicative demands and novel noun-noun compound use was explored experimentally also. Twenty-eight five-year-old children and 16 adults participated in referential and non-referential communication tasks in which they were exposed to referents whose elements were inherently and non inherently related. Both children and adults produced more compounds for inherent than for non-inherent referents. However, although the children demonstrated that they were sensitive to the need for greater communicative precision in the referential compared to the non-referential task, there was no difference in frequency of compound use across tasks. These results suggest that the functions ascribed to novel compounds warrant closer scrutiny. PMID- 8454679 TI - Evaluating quantitative measures of grammatical complexity in spontaneous speech samples. AB - The validity of MLU and a measure of syntactic complexity were tested against LARSP on spontaneous speech samples from 87 children, ranging in age from 1;6 to 4;9. Change in some LARSP clausal measures was found across MLU stages up to MLU 4.5. For the measure of syntactic complexity, no such ceiling was found for the clausal connectivity score in LARSP or for average clausal complexity in LARSP. Neither MLU nor the measure of syntactic complexity indexed LARSP phrasal complexity. It is concluded that MLU is a valid measure of clausal complexity up to 4.5 and that our measure of syntactic complexity is more valid at more advanced stages. PMID- 8454680 TI - Lexical and prosodic cues in the comprehension of relative certainty. AB - This study examined the development of children's comprehension of the use of intonation and belief verbs to mark the relative certainty with which a speaker makes a statement. Subjects were presented with a task in which they had to guess the location of an object hidden in one of two boxes over a series of trials. As clues to location, the children were presented with contrasting pairs of statements by two puppets. In the first experiment with 30 children at each of three, four, five and six years of age, statements in each pair differed either with respect to the belief term included - know, think or guess - or with respect to terminal pitch contour - rising or falling. Results showed that three-year olds did not use any information reliably to determine the location of the object, four-year-olds treated falling pitch as a more reliable indicator of location than rising pitch, and older children responded on the basis of the belief terms but not on the basis of prosody. In Experiment 2, 40 children at each of three, four and five years heard statements which differed with respect to both belief verbs and prosody. In one condition falling intonation was paired with the more certain belief term in each pair, and rising intonation with the less certain pair. In a second condition, the pairings were reversed. Results showed that, while four-year-olds could tell the difference between know and think, they could not use intonation information to determine the location. Five year-olds used both lexical and prosodic information, with prosodic cues modulating the effects of lexical. Taken together, these experiments show that prosodic and lexical cues start to be used by children to interpret relative speaker certainty at about the same time developmentally, but that lexical cues initially appear to dominate while prosodic ones modulate their effects. Finally, it is argued that children's understanding of prosody will be best revealed in contexts in which they are required to respond to the pragmatic function of verbal stimuli rather than to the lexical content. PMID- 8454681 TI - The past conditional verb form in French children: the role of semantics in late grammatical development. AB - As shown by Bowerman (1986), it has proved remarkably difficult to find clear-cut interpretations of why children face problems with conditionals. The present study reassesses a part of this puzzle by analysing four- to eight-year-old French children's acquisition of conditional verb forms. Relevant data in the literature and results of an experiment designed to gain information on the temporal meaning of young children's past conditional verb forms are presented and discussed. Among others, they are shown to provide weak support for interpretations stressing the role of conceptual problems and related mapping problems. Meeting one of Slobin's (1985) proposals, an interpretation is suggested that views the lateness of the past conditional verb form as due to an unexpected juxtaposition of 'possibility' and 'non-possibility' in its semantic representation. It is argued that such a juxtaposition cannot be achieved on the sole basis of cognitive development and that it requires the preliminary mastery of the conditional verb form. PMID- 8454682 TI - Interactive influences on phonological behaviour: a case study. AB - An infant girl's unusual phonological behaviour was evaluated in the light of a maternal model which appeared to exaggerate features of normal conversational speech. It is suggested that parental responses to immature speech patterns may account for selected case study behaviours which have been reported in both the child phonology and child fluency literatures. It appears that evaluation of phonological development within an interactive framework may allow a more accurate picture of the conditions under which children learn speech skills. To this end, further study of the phonetic characteristics of input language and patterns of parental feedback to early articulatory attempts is desirable. PMID- 8454683 TI - When is communication a meeting of minds? AB - Do infants and young children (two-year-olds) possess an implicit theory of mind which is revealed through their communicative interactions or are they simply treating their interlocutors as objects to manipulate in service to their own material ends? Shatz & O'Reilly (1990) criticized a paper by Golinkoff (1986) for claiming that infants were attempting to communicate as opposed to simply manipulate their listeners. This paper takes exception to that argument. It reviews additional evidence which indicates that infants in the second year of life are capable of communicating for the sake of the 'meeting of minds'. The alternative--treating young children's communications as only the firing off of conversational routines for the purpose of attaining material ends--seriously underestimates infants' knowledge of the communicative process. PMID- 8454684 TI - Perfecting research techniques in an imperfect world: response to MacWhinney & Snow. AB - Edwards (1992c) concerns data and data use rather than manuals. It presents principles to facilitate reliable archive research in an imperfect world. MacWhinney & Snow (1992) endorse the principles but disagree on important details, discussed in this response. M&S underrate the impact of corpus inconsistencies on substantive conclusions. Since acquisition research concerns events which often trickle in a few at a time, main findings often involve a handful of examples, so overlooking a single early variant can seriously skew results. Until archives become perfect, if they do, type-token listings can help in identifying variants before computer search and avoiding this hazard. PMID- 8454685 TI - Identifying formulas in first language acquisition. AB - With the increase in interest in formulas, or apparently non-productive utterances in children's speech, a range of definitions has emerged and sometimes conflicting criteria have been proposed for their identification. These definitions of formulas are compared, and the criteria of Brown (1973), Wong Fillmore (1976), Peters (1983) and Plunkett (1990) for the recognition of formulas are reviewed. A preference rule system is proposed, which distinguishes necessary, typical and graded conditions for the recognition of formulas. Using these conditions, some of the formulas found in the data of one child acquiring Irish between 1;4 and 2;1 are examined. Issues such as length of units, frequency of occurrence and appropriateness of use are discussed. The methods developed in this study could be used to assess the importance of formulas in the language acquisition of other children. PMID- 8454686 TI - Lexical segmentation and vocabulary growth in early language acquisition. AB - The identification of appropriate lexical segmentations of the speech signal constitutes a problem for the language learner and the child language researcher alike. Articulatory precision and fluency criteria for identifying formulaic expressions, sub-lexical forms and target lexemes in linguistic productions are defined and applied to the analysis of two Danish children's language development between the ages of 1;0 and 2;0. The results of this analysis are compared to the results of applying standard distributional and frequency criteria in the tabulation of mean length of utterance and vocabulary profiles for both standard and non-standard lexical segmentations. It is argued that although the two methods yield converging profiles of development during the latter part of the period studied, articulatory precision and fluency criteria offer a more powerful tool for identifying alternative segmentation strategies in early language acquisition. Profiles of vocabulary development for these two children suggest that the solution to the segmentation problem may be an important trigger for their vocabulary spurts. PMID- 8454687 TI - Nouns in early lexicons: evidence, explanations and implications. AB - Many theories of grammatical and lexical acquisition assume that children learn predominantly nouns, and specifically names of objects, when they first begin to acquire words in the second year. We show that the noun bias in early vocabularies is far from universal, and that it rests only in part on the acquisition of object names. An analysis of vocabulary composition from 45 children at 1;8 indicates that more nouns are acquired than all other word classes, but that of the nouns acquired only about half are the names of basic level object classes (BLOCs). An examination of the use of nouns in mother-child discourse shows that non-object words referencing locations, actions and events, for example, are used in distinctive pragmatic and grammatical contexts which might enable a child to grasp the word's use and eventually its meaning. It is concluded that a theory of lexical acquisition in discourse context is required to explain word learning at all levels and for all word types. Implications for semantic bootstrapping theories are considered. PMID- 8454688 TI - Noun bias in maternal speech to one-year-olds. AB - This study examines the distribution of nouns and verbs in maternal speech to one year-olds. Mothers and children were videotaped during toy play and non-toy play. Nouns and verbs in maternal speech were coded for frequency, sentence position and occurrence with grammatical inflections. Maternal speech was also coded for utterances that prompted the child to produce a noun or a verb. Frequency of nouns and verbs varied with context. There were more noun types and tokens during toy play, and more verb types and tokens during non-toy play. Nouns occurred more often than verbs in shorter maternal sentences, in sentence-final position, and with fewer grammatical inflections. Mothers also more often prompted their children to produce nouns. There was a significant positive correlation between frequency of noun types and tokens during toy play, and the proportion of nouns in children's first 50 words. PMID- 8454689 TI - Determination of catecholamines in rat heart tissue and plasma samples by liquid chromatography with electrochemical detection, by B.-M. Eriksson and B.-A. Persson, J. Chromatogr., 228 (1982) 143. PMID- 8454690 TI - Determination of mitomycin C, 2,7-diaminomitosene, 1,2-cis- and 1,2-trans-1 hydroxy-2,7-diaminomitosene in tumour tissue by high-performance liquid chromatography. AB - A high-performance liquid chromatographic method is described for the determination of mitomycin C (MMC) and its metabolites 2,7-diaminomitosene (2,7 DM), 1,2-cis-1-hydroxy-2,7-diaminomitosene (cis-hydro) and 1,2-trans-1-hydroxy 2,7-diaminomitosene (trans-hydro) in tumour tissue. N-la-Methylmitomycin C (porfiromycin, PM) was used as an internal standard. Two factors were critical in resolving the metabolites: pH and buffer ionic strength, where the retention times of the four components were affected in the order 2,7-DM >> cis-hydro >> trans-hydro >> MMC. The optimal isocratic conditions (flow-rate 1 ml/min) were 18 mM sodium phosphate pH 5.8-methanol (74:26) and a column temperature of 40 degrees C on a Spherisorb ODS-2 column (25 cm x 4.6 mm I.D.). Liquid-liquid extraction [twice with chloroform-propan-2-ol-ethyl acetate (2:2:1)] is described for tumour tissue. Recoveries varied depending on the component: MMC, 71.9 +/- 12.4%; PM, 85.5 +/- 27%; 2,7-DM, 51.7 +/- 5.4%; cis-hydro, 52.0 +/- 16.8%; trans hydro, 62 +/- 8%. When applied to the analysis of a rat mammary carcinoma treated intra-tumourally with 450 micrograms of MMC five drug-related "metabolite" peaks were detected. Three of these co-chromatographed with standards of 2,7-DM, cis- and trans-hydro, and had identical absorption maxima to their respective standards, with the possible exception of trans-hydro. PMID- 8454691 TI - Determination of aditoprim and its oxidative metabolites in plasma and microsomal incubation mixtures by high-performance liquid chromatography. AB - A high-performance liquid chromatographic method is presented for the determination of aditoprim (ADP) and its two oxidative metabolites in biological fluids including sheep plasma and the incubation medium of liver microsomes. The compounds were separated using a highly deactivated C18 column; the mobile phase consisted of an 0.05 M phosphate buffer (pH 6) and acetonitrile in a ratio of 90:10 (v/v). The eluate was quantified by ultraviolet detection at 230 nm. Calibration curves were linear from 0.25 to 5 micrograms/ml. The limit of detection was 0.05 microgram/ml. In an in vivo kinetic study in sheep, N monodesmethyl-ADP and N-didesmethyl-ADP appeared to be equally important metabolites. In contrast, in in vitro metabolism studies using liver microsomes from different animal species including sheep, N-didesmethyl-ADP was formed predominantly. PMID- 8454692 TI - High-performance liquid chromatographic method for the simultaneous determination of pentisomide and its major metabolite N-desisopropylpentisomide in plasma, urine and tissues using solid-phase extraction. AB - A rapid, sensitive and selective high-performance liquid chromatographic method for the simultaneous determination of pentisomide and its major metabolite desisopropylpentisomide in plasma, urine and tissues has been developed. The method for plasma samples, urine samples and tissue samples, after homogenizing with 50% ethanol, involves extraction of samples via activated Bond-Elut C8 disposable columns with methanol at pH 10 after addition of internal standard, and initially on column washing of samples at pH 10 with water and acetonitrile. The obtained methanolic extract is evaporated to dryness under nitrogen at 25 degrees C; the sample residue is then reconstituted in mobile phase and an aliquot of this solution is injected into the liquid chromatograph. Separation is performed using a Nova-Pak C18 4 microns particle size column operating in combination with radial compression separation unit and a methanol-water-di-sec. butylamine-phosphoric acid (40:60:0.5:0.2, v/v) pH 3.5 mobile phase with ultraviolet detection at 258 nm. Endogenous substances or a variety of drugs concomitantly used in pentisomide therapy, with the exception of disopyramide, do not interfere with the assay. The mean recovery of pentisomide and desisopropylpentisomide from plasma and urine and from tissues is more than 91 and 86%, respectively. The limit of detection of the assay is 10 ng/ml for both drugs. The intra- and inter-day coefficient of variation for replicate analyses of spiked plasma samples is less than 7 and 8%, respectively. Mean steady-state plasma levels of pentisomide and desisopropylpentisomide in patients on chronic oral therapy are reported. PMID- 8454695 TI - Simple microscale high-performance liquid chromatographic method for determination of furosemide in neonatal plasma. AB - A simple microscale high-performance liquid chromatographic method using fluorescence detection for the quantitation of furosemide in neonatal plasma is described. Sample pre-treatment involved protein precipitation of 25 microliters of plasma with 100 microliters of acetonitrile. The mobile phase consisted of acetonitrile (460 ml) and 0.08 M orthophosphoric acid (540 ml) and was delivered at 1.1 ml/min. Calibration curves were linear from 0.1 to 25 micrograms/ml. Within-day and between-day imprecision (coefficient of variation) was 3.9-6.1, and 6.1-12.2%, respectively. Furosemide was eluted after 6.5 min and naproxen (internal standard) after 11.5 min. The assay was validated for application in neonatal plasma containing a wide range of albumin concentrations. PMID- 8454694 TI - Biocytin synthetase activity in human milk as assessed by high-performance liquid chromatography. AB - A reversed-phase liquid chromatographic assay for biocytin synthetase activity has been developed. By this method, biocytin synthetase, isolated to homogeneity from human milk, was found to synthetize biocytin from biotin and L-lysine in the presence of ATP and magnesium ion(s). Both ATP and magnesium ion(s) were required for the synthesis of biocytin. Equal molar amounts of ADP and ATP were produced and consumed, respectively, in the course of the production of the same molar amount of biocytin; however, production of AMP was not observed. Biocytin synthetase Michaelis constants were 2.5, 1.8, and 0.11 mM for biotin, L-lysine, and ATP, respectively. Biocytin synthetase from milk was shown to synthesize biocytin in a stoichiometric amount. PMID- 8454693 TI - Peak distortion effects of suramin due to large system peaks in bioanalysis using ion-pair adsorption chromatography. AB - Sample injections in ion-pair adsorption chromatography lead to changes in the established equilibria of the eluent components at the top of the column, which in turn lead to migrating concentration changes in the column (system peaks). Large system peaks contain big concentration deviations of the mobile phase components compared with the bulk composition in the eluent. Analyte peaks are distorted upon combined elution with large system peaks. In bioanalysis, samples that deviate considerably from the eluent are often injected, resulting in large system peaks. An illustrative example of such analyte peak distortions in bioanalysis is given for the case of suramin, and guidelines are given for avoiding the effects. PMID- 8454696 TI - Sensitive high-performance liquid chromatographic assay for the determination of chlorhexidine in saliva. AB - A high-performance liquid chromatographic assay was developed to determine salivary chlorhexidine concentration. Saliva sample (200 microliters) was extracted into methylene chloride. Chromatographic separation was achieved with a C18 column using a mobile phase of acetonitrile-0.05 M sodium acetate and 0.005 M heptanesulfonic acid (40:60, v/v). The standard curve was linear from 0.051 to 20.48 micrograms/ml (r2 > or = 0.997). Intra-day and inter-day coefficients of variation were < 5.5 and < or = 9%, respectively. The assay is rapid, sensitive, simple, and successfully used for quantitating salivary chlorhexidine content released from a chlorhexidine-impregnated resin worn by patients. PMID- 8454697 TI - Reproducible and high-speed separation of basic drugs by capillary zone electrophoresis. AB - The complete separation of a mixture of seventeen basic drugs of different classes was achieved with capillary zone electrophoresis in 11 min. The migration time reproducibility for individual components was between 0.5 and 1.7% relative standard deviation (R.S.D.). Peak detection was achieved by ultraviolet absorption, with peak-area reproducibility ranging from 1.5 to 6.3% R.S.D. The pH of the running buffer was critical in determining the separation of the mixture of basic drugs. The detection of most of these components in urine and plasma is also illustrated. PMID- 8454698 TI - Gas chromatographic determination of alkyl lysophospholipids after solid-phase extraction from cell culture media. AB - The gas chromatographic determination of 1-O-octadecyl-2-O-methyl-DL-glycero-3 phosphorylcholine (Et-18-OMe), an anti-invasive alkyl lysophospholipid, in cell culture media is described. Sample clean-up was performed by solid-phase extraction on a weak cation-exchange column of the CBA type (carboxylic acid). For quantitation, the structural analogue Et-16-OMe as the internal standard was used after derivatization with trimethylsilyl bromide. The described method was free of interferences in cell culture media. The overall precision for twenty determinations was 14.99%. PMID- 8454699 TI - High-performance liquid chromatographic assay of platelet-produced thromboxane B2. AB - A method for the routine determination of platelet-produced thromboxane B2 (TXB2) from human serum is presented. To induce the secretion of thromboxane A2 from the platelets, blood is kept at 37 degrees C for 30 min before serum is separated. Serum is prepurified through small reversed-phase columns and TXB2 is analysed by reversed-phase high-performance liquid chromatography. A column-switching technique is used to remove the interfering compounds present in serum. The detection limit with standard solution is 30 ng per injection. The method was applied to the measurement of platelet-produced TXB2 serum from 1040 men. The mean TXB2 was 247 +/- 134 ng/ml in the serum of men who had not used prostaglandin inhibitors, and 208 +/- 123 ng/ml in the serum of men who had used a prostaglandin inhibitor during a two-week period before blood sampling. PMID- 8454700 TI - Determination of corticosteroids in plasma by high-performance liquid chromatography after pre-column derivatization with 2-(4-carboxyphenyl)-5,6 dimethylbenzimidazole. AB - 2-(4-Carboxyphenyl)-5,6-dimethylbenzimidazole (CDB) was used as a pre-column derivatization reagent for corticosteroids analysed by high-performance liquid chromatography with fluorimetric detection. Eight corticosteroids were derivatized with CDB to their esters in acetonitrile containing 4 piperidinopyridine and 1-isopropyl-3-(3-dimethylaminopropryl)carbodiimide perchlorate. The resulting CDB esters were extracted with a Sep-Pak C18 cartridge and the esters were separated on a reversed-phase column (Zorbax ODS) with water methanol (25:75, v/v) containing 5 mmol/l tetramethylammonium hydrogensulphate as the mobile phase. The limits of detection for steroids were 0.06-0.3 pg per 100 microliters of plasma (signal-to-noise = 3). The within-day relative standard deviations (n = 6) were 7.8-11.1%, and day-to-day relative standard deviations (n = 6) were 7.0-10.4%. PMID- 8454701 TI - Assay of pyridinium crosslinks in serum using narrow-bore ion-paired reversed phase high-performance liquid chromatography. AB - The pyridinium crosslinks are important biomarkers of mature hard tissue collagen degradation. This paper describes an isocratic ion-paired reversed-phase high performance chromatographic assay using narrow-bore columns and high-sensitivity fluorescence detection to enable for the first time the determination of pyridinium crosslinks in both serum and synovial fluid samples. Extracted freeze dried acid hydrolysates were re-suspended in 20 mM pentafluoropropionic acid (PFPA). Separations were carried out using an Exsil 100 5-microns ODS2 column (100 mm x 2.1 mm I.D.) eluted with 10 mM PFPA in water at 0.15 ml/min and detected using a Jasco 821-FP detector (xenon lamp: excitation 290 nm, emission 400 nm). Fluorescent response was linear from 269 to 8620 fmol for pyridinoline (Pyr) and 85 to 2710 fmol for deoxypyridinoline (dPyr). The limits of detection were 28 and 57 fmol, respectively. The coefficient of variation for extraction and analysis of normal serum was 7.96% for Pyr and 6.30% for dPyr (n = 6). The mean +/- S.D. concentration of Pyr in normal serum was 3.26 +/- 0.83 nM. PMID- 8454702 TI - Application of a new statistical approach to optimize the immunopurification of antihemophilia A factor. AB - Our aim was to optimize the immunopurification process of human factor VIII. This purification was performed using a mouse monoclonal anti-factor VIII light-chain antibody. Previous dissociation of the factor VIII-von Willebrand factor complex with CaCl2 led to a 50% increase of the factor VIII adsorption on the immunosorbent. The optimization of the elution step required the analysis of the effects of two parameters, pH and ionic strength, on four different responses: elution yield, concentration, specific activity and stability of factor VIII. For this purpose, a multifunctional method using Doehlert matrices for statistically designed experiments was applied. This methodology allowed us to obtain, with only seven experiments, a 60% increase of the elution yield and a two-fold increase of the specific activity of factor VIII. PMID- 8454703 TI - Chromatographic separation of glycated nucleotides. AB - A high-performance liquid chromatographic method for the separation of nucleotide glycation reaction product(s) has been developed. The product(s) arising during in vitro glycation of a nucleotide (AMP, GMP or CMP) with a reducing sugar (ribose or glucose) were clearly resolved from the non-glycated constituents of the reaction mixture. The peak(s) of the glycated product(s) increased when an amino acid (lysine, arginine, beta-alanine or N epsilon-acetyllysine) was added to the reaction mixture. This increase probably corresponds to the formation of a new product with a different absorption maximum (250 versus 260 nm). Conversely, formation of this product(s) was inhibited by the presence of the metal-chelating agent diethylenetriamine pentaacetic acid and by aminoguanidine. PMID- 8454704 TI - Determination of plasma ascorbic acid by high-performance liquid chromatography with ultraviolet and electrochemical detection. AB - A convenient and reliable reversed-phase liquid chromatographic method for the routine determination of ascorbic acid with ultraviolet detection is described. This system avoids the use of modifier and ion-pairing reagent. The mobile phase consists of 20 mM ammonium dihydrogenphosphate with 0.015% metaphosphoric acid. This method enables the detection of plasma ascorbic acid at a concentration of 120 ng/ml within 5 min. The recovery and reproducibility were above 95%. A comparative study was also performed using ultraviolet and electrochemical detectors. Excellent agreement was observed between the two detection modes, with a correlation coefficient of 0.99. In addition, the storage conditions and stability of ascorbic acid in plasma and whole blood were investigated. The results showed that ascorbic acid was more stable in whole blood when stored below 4 degrees C. PMID- 8454705 TI - Gas chromatography-mass spectrometry determination of 18O2 in 18O-labelled 4 hydroxyproline for measurement of collagen synthesis and intracellular degradation. AB - The use of gas chromatography-mass spectrometry (GC-MS) and 18O2, a stable isotope which is incorporated into collagen during the post-translational conversion of proline to hydroxyproline, offers the potential advantages of high levels of sensitivity and specificity as compared to other techniques for measuring rates of collagen synthesis and degradation in vitro and vivo. Trifluoracetylation and methanol esterification of hydroxyproline yields two derivatives of hydroxyproline: N,O-trifluoroacetyl methyl 4-hydroxy-L-proline (N,O-TFA-Hyp) and N-trifluoroacetyl methyl 4-hydroxy-L-proline (N-TFA-Hyp). In the past, N-TFA-Hyp, which yields the 16O/18O-containing m/z 182/184 ion pair [M COOH3]+ when analyzed by electron impact ionization GC-MS, has been proposed for analysis of 18O-enriched collagen. Although N,O-TFA-Hyp can be converted to N-TFA Hyp by solvolysis, we find that this leads to degradation of the chromatography in GC-MS and demonstrate here that this extra chemical step is unnecessary if the m/z 278/280 ion pair (representing the [M-COOCH3]+. fragment) is measured by selected ion monitoring. By labelling fibroblasts in culture with 18O2, a sample of isotope-enriched collagen was obtained which was used to calibrate the GC-MS over the range 0.5-49% atom percent enrichment (APE). The greater sensitivity of 18O2 versus [15N]proline for labelling newly synthesized collagen was demonstrated by the finding of a ten-fold higher enrichment in the former isotope when administered to cell cultures at the same precursor APE. Thus, the approach described herein permits the determination of total hydroxyproline and APE on the same sample avoiding additional processing steps while maintaining the quality of chromatography and the sensitivity of detection. Measurement of absolute rates of both collagen synthesis and intracellular degradation of newly synthesized collagen in cell cultures is thus possible. Preliminary results comparing collagen metabolism in pairs of fibroblasts from hypertrophic scars and normal skin in post-burn patients are presented. PMID- 8454706 TI - Estimation of the lower limit of quantitation, a method detection performance parameter for biomedical assays, from calibration curves. AB - A model for the lower limit of quantitation for biomedical chromatographic assays is proposed. It is based on the IUPAC definition for the limit of detection and can be estimated from assay calibration data. It has been applied to ten different sets of calibration data from various assays of drugs in biological matrices. PMID- 8454707 TI - Determination of leucovorin and 5-fluorouracil in plasma by high-performance liquid chromatography. AB - A method was developed for the determination of (6R)- and (6S)-leucovorin and 5 fluorouracil in plasma. As leucovorin diastereoisomers cannot be separated on a classical reversed-phase column, it was necessary to use a chiral stationary phase. The method presented is based on the same principle as the method described by Wainer and Stiffin [J. Chromatogr., 424 (1988) 158], i.e., coupling of a bovine serum albumin phase to an achiral stationary phase. Before the chromatography, the drug was isolated from the plasma matrix by solid-phase extraction. For 5-fluorouracil, chromatography was performed on a classical RP-18 column after extraction from the plasma by liquid-liquid extraction. Both methods were validated and applied to the analysis of patients' samples. PMID- 8454708 TI - High-performance liquid chromatography of imipramine and six metabolites in human plasma and urine. AB - A method for the simultaneous quantitation of imipramine and six metabolites (2- and 10-hydroxyimipramine, 2- and 10-hydroxydesipramine, didesmethylimipramine and desipramine) in human plasma and urine has been developed. The method is based on a three-step liquid-liquid extraction followed by isocratic, reversed-phase high performance liquid chromatography with ultraviolet absorbance detection (detection wavelength: 220 nm). The chromatographic eluent consisted of 30% acetonitrile and 70% aqueous sodium perchlorate solution pH 2.5. Glucuronide conjugates in urine were deconjugated with beta-glucuronidase/arylsulphatase prior to extraction. PMID- 8454709 TI - Selective method for plasma quantitation of the stereoisomers of a new aminotetralin by high-performance liquid chromatography with electrochemical detection. AB - A high-performance liquid chromatographic method is described for the quantitation in plasma of the four stereoisomers of a new aminotetralin, (SRR, RSS)(SRS, RSR)-5,6-dimethoxy-2-[3'-(p-hydroxyphenyl)-3'-hydroxy-2'- propyl]aminotetralin (CHF 1255, internal code). After liquid-liquid extraction of the drug, separation was obtained after chiral derivatization with R-(+)-alpha methylbenzyl isocyanate. The selective derivatization of the amino group was obtained by controlling the pH of the reaction medium at 7.5. The reaction was quantitative after a period of 16 h. The structures of the urea derivatives were confirmed by proton nuclear magnetic resonance spectroscopy and high-performance liquid chromatography with mass spectrometric detection. The use of an electrochemical detector, operating in the oxidative mode, allows the quantitation in plasma of all four urea derivatives at the nanogram level. The method was demonstrated to be precise, reproducible and applicable to pharmacokinetics studies after administration of the two epimeric racemates. PMID- 8454711 TI - 16th International Symposium on Column Liquid Chromatography. Baltimore, Maryland, June 14-19, 1992. Proceedings. Part II. PMID- 8454710 TI - Isolation of plasma proteins from the clotting cascade by heparin affinity chromatography. AB - The use of heparin affinity chromatography for the isolation of plasma proteins from the clotting cascade is described. The separation is carried out with heparin agarose and, in parallel operations, with different rigid gels on a polymer base. The quality of the separation and the reproducibility of the results were investigated and the stability of the materials at high pH was tested. The affinity supports were used for the isolation of antithrombin III from human plasma and for the separation of factor IX from factor X, after partial purification by anion-exchange chromatography. The isolation of antithrombin III from human plasma served as a model. The non-specific bindings were investigated, together with the resistance of the support when treated with 0.2 and 0.5 M sodium hydroxide. Heparin agarose has low non-specific bindings, but it cannot be exposed to high pH. The supports on a polymer base are resistant to high pH, up to 13.7. However, they may remain slightly hydrophobic, and the hydrophobicity of the matrix leads to an increase in non-specific bindings. When antithrombin III is isolated, the non-specific bindings result in contamination of the final product. The lack of resistance of the matrix at high pH causes a weaker binding of antithrombin III, and the product is eluted at lower and lower sodium chloride concentrations. The results can be indicative of the behaviour of the support in the separation of factor IX from factor X. High non-specific bindings will lead to contamination of the factor IX product and consequently to low specific activity. Insufficient resistance of the support at high pH will result in failure to separate the two clotting factors satisfactorily. The separation can be monitored by heparin high-performance membrane affinity chromatography (HPMAC). Contamination of the sample, which occur in sodium dodecyl sulphate-polyacrylamide gel electrophoresis are detected within minutes by fast heparin HPMAC. PMID- 8454713 TI - High-performance liquid chromatography of amino acids, peptides and proteins. CXXII. Application of experimentally derived retention coefficients to the prediction of peptide retention times: studies with myohemerythrin. AB - Amino acid retention coefficients were derived from the experimental retention data of 118 overlapping peptide heptamers related to the primary amino acid sequence of myohemerythrin. Individual retention coefficient values for each amino acid were derived by a multiple linear regression matrix approach. Retention data were derived for five different experimental conditions including different organic modifiers (acetonitrile, methanol or 2-propanol), different mobile phase additives (trifluoroacetic acid or potassium phosphate) and different silica-based stationary phase ligands (octadecyl or phenyl groups). A high degree of correlation was observed between these experimentally derived amino acid coefficients (EXP) and the coefficients (LIT) which we recently reported derived from the retention data of over 2000 peptides [M. C. J. Wilce et al., J. Chromatogr., 536 (1991) 165 and 548 (1991) 105]. These results demonstrated that the LIT and EXP coefficients can be used for the prediction of the retention of any peptide set. The effect of peptide length was also further investigated and the correlation results demonstrated the importance of peptide flexibility on the final value of the amino acid coefficient. PMID- 8454712 TI - Size-exclusion chromatographic determination of beta-glucan with postcolumn reaction detection. AB - Using the specific interaction of beta-glucan with calcofluor dye as a detection method for size-exclusion chromatographic analysis, very simple direct extractions can be used for sample preparation. Either fluorescence or UV detection is employed. The calibration graphs are linear between 200 and 20 mg/l, although much more sensitive analyses are possible. The response remained independent of relative molecular mass in the range studied (1.7 x 10(6)-1.85 x 10(5)). Results for barley and malt show good correlation with those obtained by flow-injection analysis using calcofluor. PMID- 8454714 TI - Separation of metallothionein isoforms by capillary zone electrophoresis. AB - The potential of capillary zone electrophoresis (CZE) for the analysis of metallothionein (MT) isoforms was investigated. CZE was performed using two different systems, (1) a laboratory-constructed instrument with an ISCO UV detector and (2) a Waters Quanta 4000 system. Capillaries were of 75 microns I.D. x ca. 1 m in length and loading times were up to 40 s by gravity or 4 s by electrokinetic migration at 30 kV. Samples were dissolved in 10 mM Tris-HCl buffer, pH 9.1, and electrophoresis was performed at 30 kV using a 50 mM Tris HCl, pH 9.1 running buffer. Detection was by UV absorbance at 185 or 214 nm. Purified and semipurified MT samples were analysed for qualitative assessment of purity, relative isoform abundance and separation characteristics of MT from different species. As progress towards the development of a quantitative assay, the linearity of calibration curves and simple methods of sample preparation for analysis by CZE were investigated. Complete separation of a mixture of the two major MT isoforms was achieved in less than 5 min and the technique was found to be very useful for qualitative analysis of MT. Using a rabbit liver MT standard (500 micrograms/ml-1), a linear relationship was found between the gravity load time and the integrated peak area. Standard calibration curves were also linear and the detection limit for both CZE instruments under our separation conditions was 1-10 micrograms MT ml-1. The successful use of two solvent extraction procedures for tissue samples demonstrated the potential of CZE for routine quantitative analysis of MT. PMID- 8454715 TI - Prediction of the migration behavior of organic acids in micellar electrokinetic chromatography. AB - The migration behavior of an homologous series of phenols in micellar electrokinetic chromatography is quantitatively presented. This model describes mobility in terms of fundamental physical and chemical constants of each solute (acid dissociation constant Ka, micelle binding constant Km), the pH of the buffer, and the micelle concentration ([M]) in the buffer. The model was used to predict the mobility of each solute over a two-dimensional pH/[M] space. Predicted and actual electropherograms show the usefulness of this technique. PMID- 8454716 TI - Polymer- and surfactant-coated capillaries for isoelectric focusing. AB - This paper reports a method for deactivation of fused-silica capillaries to be used in capillary isoelectric focusing (cIEF). Deactivation was achieved by adsorbing either a surfactant or hydrophilic polymer to alkylsilane-derivatized capillaries. The surfactant PF-108 and methyl cellulose reduced electro-osmotic flow (EOF) 20 to 30 fold in comparison to underivatized capillaries. Although EOF was reduced sufficiently to allow focusing to permit separations to be completed before proteins were swept through the capillary, there was adequate flow to obviate the need for a separate mobilization step. This reduces the complexity of cIEF and increases reproducibility. Based on resolution of hemoglobin variants, proteins that varied 0.03 pH units in isoelectric point were resolvable. This is equivalent to the highest resolution achieved in conventional slab and tube gel isoelectric focusing. PMID- 8454717 TI - Conformational changes of brain-derived neurotrophic factor during reversed-phase high-performance liquid chromatography. AB - Recombinant human brain-derived neurotrophic factor (r-HuBDNF) is eluted as two peaks under reversed-phase liquid chromatographic conditions with gradient elution. Sodium dodecyl sulfate polyacrylamide gel electrophoresis confirmed identical molecular weights in the two peaks, while rechromatography of the separated peaks showed interconvertibility. The two peaks are identified as the monomeric forms of the parent molecules. The molecular weight of the components in the peaks was determined by on-line 90 degree light scattering using a fluorescence detector as a scatterograph. The early eluted peak is a folded form of the r-HuBDNF monomer, while the later eluted peak is an unfolded form of the BDNF monomer. The conformational states were established using a fluorescence detector both at a fixed wavelength and in the scanning mode. PMID- 8454718 TI - Immunochromatographic analysis of proteins. Identification, characterization and purity determination. AB - Antibodies specific to a protein and its structural variants were immobilized on a high-performance Protein G column. This column recognized and selectively subtracted specific molecules from a sample. When a size-exclusion column was coupled with this high-performance affinity column, a comparison between the elution profile before and after the antibody immobilization was used to study antigen components present in the sample. Various human growth hormone structural variants and aggregates were studied using this approach. The technique is simple, fast and does not involve the usage of radioactive material. PMID- 8454719 TI - Structural characterization of glycoprotein digests by microcolumn liquid chromatography-ionspray tandem mass spectrometry. AB - An in-house modified microcolumn liquid chromatography (LC) system has been coupled to a PE-SCIEX API III triple-quadrupole mass spectrometer through an ionspray interface for the structural characterization of model glycoproteins, bovine ribonuclease B and human alpha 1-acid glycoprotein. In conjunction with enzymatic digestion approaches using trypsin and peptide-N-glycosidase F, the feasibility of packed-capillary (250 microns I.D.) LC columns, coupled with ionspray mass spectrometry (MS) in a tandem format, have been assessed for glycopeptide mapping and structural determination. This configuration demonstrates a highly promising approach for the determination of glycosylation sites and the corresponding sequence structures of related tryptic fragments. A glycosylated tetrapeptide, Asn-Leu-Thr-Lys with carbohydrate moieties on Asn-34, was readily located for bovine ribonuclease B. Preliminary results using micro-LC MS also show the identification of a class A carbohydrate attachment on a tryptic fragment of human alpha 1-acid glycoprotein. The microheterogeneity of carbohydrate moieties can be quickly screened using this approach for either tryptic digests or the intact glycoprotein. These methods demonstrate potential applications for structural characterization of recombinant glycoproteins of pharmaceutical interest. PMID- 8454720 TI - Detection of alkaloids in foods with a multi-detector high-performance liquid chromatographic system. AB - A general screening method for alkaloid drugs in foods is described based on high performance liquid chromatography with ultraviolet detection at three wavelengths, followed by fluorescence and electrochemical detectors in series. The chromatographic conditions include an ion-pairing reagent, which makes it possible to chromatograph acidic and basic drugs with one screen. Relative response ratios were determined from the peak areas of the alkaloids on the basis of all the detector signals. These ratios were used to create a "fingerprint" of the drugs and to predict the identity of an unknown component in a sample matrix. The fluorescence and electrochemical detectors allowed a detection limit for many of the alkaloids which would not be attainable with the ultraviolet detector alone. Typical detection limits with the electrochemical detector were 5-50 ng/ml and with the fluorescence detector 5-500 ng/ml, while the ultraviolet detector had detection limits of 1-20 micrograms/ml. The spiking concentrations in the relative response ratio experiments were approximately five times above the lowest detection limit. The extraction method investigated for orange juice yielded recoveries for most alkaloids of 80-100%. A stability study of ergot alkaloids in various food matrices demonstrated degradation, depending on the matrix, temperature, and duration of the experiment. PMID- 8454721 TI - Estimation of the extent of lipid peroxidation in the ischemic and reperfused heart by monitoring lipid metabolic products with the aid of high-performance liquid chromatography. AB - Estimation of lipid peroxidation (LPO) through malonaldehyde (MDA) formation measured by assaying thiobarbituric acid reactive products remains the method of choice to study the development of oxidative stress to assess myocardial ischemic reperfusion injury. However, MDA estimation by this assay is non-specific and often gives erroneous results. In this report, we describe a method to estimate MDA, formaldehyde (FDA), acetaldehyde (ADA), and acetone, the degradation products of oxygen free radicals (OFR) and polyunsaturated fatty acids (PUFA), as presumptive markers for LPO. Isolated rat hearts were made ischemic for 30 min, followed by 60 min of reperfusion. The perfusates were collected, derivatized with 2,4-dinitrophenylhydrazine, and extracted with pentane. Aliquots of 25 microliters in acetonitrile were injected on a Beckman Ultrasphere C18 (3 microns) column. The products were eluted isocratically with a mobile phase containing acetonitrile-water-acetic acid (40:60:0.1, v/v/v). The peaks were identified by co-chromatography with the hydrazine derivatives of authentic standards. The retention times of MDA, FDA, ADA and acetone were 5.0, 6.3, 9.8 and 15.7 min, respectively. The results of our study indicated progressive increase in all four lipid metabolites with reperfusion time. Thus, our results demonstrate that the release of lipid metabolites from the isolated heart increased in response to oxidative stress. Since MDA, FDA, ADA, and acetone are the products of OFR-PUFA interactions, this method allows proper estimation of LPO to monitor the oxidative stress developed during the reperfusion of ischemic myocardium. PMID- 8454722 TI - The organization of the descending ventral pallidal projections in the monkey. AB - This study describes the organization and topography of the descending efferent projections from the monkey ventral pallidum. The main efferent projections from the globus pallidus are to the subthalamus, to the thalamus, and to the substantia nigra. Although these projections have been well established for the dorsal pallidum, the projections of the ventral pallidum have not been explored in primates. The results of this study add an important link in how information from the limbic lobe is channeled through the basal ganglia in monkeys. Anterograde tracers, Phaseolus vulgaris-leucoagglutinin, and tritiated amino acids were injected into various regions of the ventral pallidum. The descending efferent projection from the ventral pallidum in monkeys terminates primarily in the subthalamic nucleus and adjacent lateral hypothalamus, in the substantia nigra, and in the lateral habenular nucleus. Although terminals are also found in the thalamus, these are relatively sparse. The projections to the subthalamic nucleus and the lateral hypothalamus are topographically arranged, while those to the substantia nigra are not. These results suggest that pathways from distinct pallidal regions that receive specific striatal input terminate in distinct regions of the subthalamic/hypothalamic regions, thus maintaining a topographic arrangement. Projections to the substantia nigra, however, overlap extensively, suggesting convergence of terminals from different ventral pallidal regions. The relatively small projection to the thalamus raises the question that without a prominent thalamic projection, is this system parallel to that described for the dorsal globus pallidus? PMID- 8454723 TI - Mapping of octopamine-immunoreactive neurons in the central nervous system of the lobster. AB - It has been suggested that serotonin and octopamine serve important roles in behavioral regulation in lobsters. In this paper the locations of octopamine immunoreactive neurons were mapped in wholemount preparations of the ventral nerve cord of 4th stage lobster (Homarus americanus) larvae. Approximately 86 neurons were found, distributed as follows: brain, 12; circumesophageal ganglia, 2; subesophageal ganglion, 38; thoracic ganglia, 6 each; and 4th and 5th abdominal ganglia, 2 each. All the octopamine-immunoreactive neurons are paired and located along the midline. Of the 86 neurons, 28 were identified as neurosecretory, and 26 as intersegmental ascending thoracic, ascending abdominal, or descending interneurons. The neurosecretory system is arranged segmentally and located entirely within the thoracic and subesophageal neuromeres with extensive terminal fields of endings along 2nd thoracic and subesophageal nerve roots. This set of neurons shares the features of central and peripheral endings with 2 pairs of large serotonin-containing neurosecretory neurons found in the fifth thoracic and first abdominal ganglia. The intersegmental neurons include: (1) two cells in the brain and 2 pairs of cells in the 3rd and 4th neuromeres of the subesophageal ganglion, which project to the 6th abdominal ganglion; (2) a segmentally organized group of ascending interneurons found in the subesophageal and in all thoracic ganglia; and (3) pairs of ascending interneurons found in the 4th and 5th ganglia in the abdominal nerve cord. By means of a biochemical assay, the cell bodies of octopamine-immunoreactive neurosecretory cells in the thoracic segment of the nerve cord were found to contain 40-100 fmol of octopamine, while control neurons had none. PMID- 8454724 TI - The projections of intracellularly labeled auditory nerve fibers to the dorsal cochlear nucleus of cats. AB - The cochlear nucleus receives incoming auditory nerve discharges, preserves or transforms the signals, and distributes outgoing activity to higher centers. The organization of auditory nerve input to the cochlear nucleus will heavily influence the mechanisms by which acoustic information is processed. In order to study structure-function relationships between auditory nerve and cochlear nucleus, the axonal arborizations of type I spiral ganglion cells were labeled with intracellular injections of horseradish peroxidase after first being electrophysiologically characterized by recording with a micropipette inserted into the axon. For each auditory nerve fiber, spontaneous discharge rate (SR) and a frequency tuning curve were determined. The tuning curve yielded the characteristic frequency (CF, that frequency to which the fiber is most sensitive) and CF threshold in dB SPL. Individual axonal arborizations including all terminal swellings were reconstructed through serial sections with the aid of a light microscope and drawing tube. On average, 13.4 +/- 8.1% of the terminal swellings were found in the dorsal cochlear nucleus (DCN) and the remaining terminal swellings were located in the ventral cochlear nucleus. In the DCN, the terminal fields of auditory nerve fibers were restricted to layer III, contributed to cytoarchitectonic striations, and exhibited a systematic relationship between fiber CF and position along the strial (or long) axis of the nucleus. Computer-aided rotations revealed that the terminal fields were anisotropic, being flattened within the trans-strial axis. The maximal width of the terminal fields along the strial axis ranged from 31-321 microns and was inversely related to fiber CF and SR. Variation in the number of terminals or depth of the terminal field within layer III was not related to SR grouping or CF of the fiber. PMID- 8454725 TI - Frequency organization of the dorsal cochlear nucleus in cats. AB - Sensory epithelia are often spatially reiterated throughout their representation in the central nervous system. Differential expression of this representation can reveal specializations of the organism's behavioral repertoire. For example, the nature of the central representation of sound frequency in the auditory system has provided important clues in understanding ecological pressures for acoustic processing. In this context, we used electrophysiological techniques to map the frequency organization of the dorsal cochlear nucleus in nine cats. Frequency responses were sampled in increments of 100-200 microns along electrode tracks that entered the dorsomedial border of the nucleus and exited at the ventrolateral border. Electrode tracks were oriented parallel to the long (or strial) axis of the nucleus so that each penetration sampled neural responses for most of the cat's audible frequencies and remained in or near the pyramidal cell layer for several millimeters. Nearly identical distance versus frequency relationships were obtained for different rostral-caudal locations within the same cat as well as for different cats. Frequency responses systematically decreased from above 50 kHz at the most dorsomedial locations in the nucleus to below 1 kHz in the most ventrolateral regions. The rate of frequency change was roughly three times greater in high frequency regions than in low frequency regions. In addition, the highest pyramidal cell density and longest rostral caudal axis was observed for the middle third of the dorsal-ventral axis of the nucleus. As a result, roughly half of all pyramidal cells responded to frequencies between 8-30 kHz. The representation of neural tissue for these frequencies may be related to the importance of spectral cues in sound locations. PMID- 8454726 TI - OFF-alpha and OFF-beta ganglion cells in cat retina. I: Intracellular electrophysiology and HRP stains. AB - Six OFF-alpha ganglion cells and a single OFF-beta ganglion cell were penetrated with intracellular microelectrodes and marked with horseradish peroxidase (HRP) in a perfused cat eyecup. Gaussian center radii (Rc) ranging from 40 to 217 microns were measured for receptive fields mapped with slits, values in agreement with previous extracellular reports. ON and OFF response components revealed nearly identical Rc's and center locations. Although Gaussian diameters (2Rc) were about 80% of dendritic field diameters overall, in this sample dendritic and receptive fields were not well correlated. Spatial tuning of ganglion cells was evidenced in peaked amplitude-vs.-width functions, fit by difference-of-Gaussians models. Such plots yielded Rc values about 40% less than position-vs amplitude plots. Rs values for surrounds ranged from 200 to 1,700 microns. Rod and cone signals were investigated with flicker. Rod flicker signals in OFF-alpha cells were larger and of shorter latency than in either horizontal or AII amacrine cells. Cone flicker signals were also short in latency, with an ON response time constant of 9 msec, and an OFF response time constant of 3 msec. The OFF-alpha rod-cone transition involved a latency increase of 20-30 msec. The spontaneous and light-evoked impulse rates of OFF-alpha responses varied linearly with extrinsic current, but the amplitude of ON hyperpolarization was little affected. After injection of staining current, the OFF-beta cell transiently depolarized at ON, suggestive of ON inhibition with reversed chloride gradient, a result not seen in OFF-alpha responses. Events (peaked, depolarizing voltage fluctuations) of high, low, and intermediate amplitudes were studied in OFF-alpha responses. High amplitude events (impulses), were OFF-correlated with the stimulus, and exhibited mean rise times (transit time from 25 to 75% of peak amplitude) from 255 to 392 microseconds. Intermediate level events (presumed synaptic origin) were also OFF correlated and had longer rise times (325 microseconds to 1.56 microseconds). Low level events (234-685 microseconds) revealed either ON, ON/OFF, or not stimulus correlation. PMID- 8454727 TI - OFF-alpha and OFF-beta ganglion cells in cat retina: II. Neural circuitry as revealed by electron microscopy of HRP stains. AB - An OFF-center alpha and an OFF-center beta ganglion cell in cat retina, which had been recorded from and intracellularly stained with horseradish peroxidase (HRP) were examined by serial section electron microscopy. We counted synapses and identified presynaptic neurons to the HRP-stained cells in 20 microns radial slices through the centers of their dendritic trees. Presynaptic amacrine and bipolar cells were identified on cytological criteria known from previous studies. The OFF-beta cell with a 62 microns dendritic arbor, restricted to S1 and S2 (sublamina a) of the inner plexiform layer (IPL), received 38% bipolar and 62% amacrine cell synapses. The bipolar input was from both cb1 and cb2 cone bipolar types. Input from three distinct amacrine cell types occurred upon the dendrites, namely from: (1) AII amacrine lobular appendages, (2) large pale amacrine profiles (possibly A2 or A3 cells), and (3) small, dark amacrine types (possibly A8 cells). Large pale amacrine profiles (possibly A13) were found on the cell body and apical dendrite in sublamina b of the IPL. In addition, several amacrine profiles synapsed directly on the sides and base of the cell body in the ganglion cell layer. We estimate that the complete dendritic tree of this beta cell received about 1,000 synapses contributed by 12-14 bipolar cells, 7-10 AII amacrines and 28-41 other amacrine cells. The OFF-alpha cell had a dendritic tree size of 680 x 920 microns. A 250 microns length of two major dendrites stratifying narrowly in S2 of the IPL was reconstructed. Amacrine cells provided most of the synaptic input (80%). This input came from: (1) AII amacrine lobular appendages, (2) amacrines exhibiting large, pale synaptic profiles (possibly A2 or A3 cells), (3) pale amacrines with large mitochondria and a few neurotubules (unknown type), and (4) densely neurotubule-filled amacrine profiles (possibly A19 cells). A large pale amacrine cell type (possibly A13) provided synaptic input to the cell body as a serial synaptic intermediary with rod bipolar cells. Cone bipolar synapses were from only one type of cone bipolar, the cb2 type and formed 20% of the total synaptic input. We estimate that a minimum of 142 bipolar cells, 256 AII amacrine cells and 1,011 other amacrine cells, altogether providing 6,000-10,000 synapses, converged on the dendritic tree of this OFF alpha cell. PMID- 8454728 TI - Connections between the deutocerebrum and the protocerebrum, and neuroanatomy of several classes of deutocerebral projection neurons in the brain of male Periplaneta americana. AB - The topography and neuroanatomy of fibers connecting the deutocerebrum to the protocerebrum in the brain of the American cockroach Periplaneta americana were investigated by staining single or multiple deutocerebral neurons with cobalt, Lucifer Yellow, or biocytin. Five tracts are distinguished on the basis of their routes from origins in the antennal lobe to the protocerebral neuropil: the inner antenno-cerebral tract (IACT); antenno-cerebral tracts II, III, and IV (ACT II, III, IV), and the outer antenno-cerebral tract (OACT). These tracts are largely composed of the axons of four classes of deutocerebral projection neurons, which have been identified morphologically; the neuronal arborizations in the glomeruli of the antennal lobe and in the protocerebral projection regions have been examined. Projection neurons with processes in the inner antenno-cerebral tract and in the antenno-cerebral tract II each innervate a single glomerulus in the antennal lobe, and both types have terminals in the calyces of the mushroom bodies and in the lateral lobe of the protocerebrum. The axons of pheromone sensitive projection neurons with dendritic trees in the male-specific macroglomerulus seem to run exclusively in the inner antenno-cerebral tract. Subgroups of these pheromone sensitive neurons differ in relative sensitivity to the two female attractant components as well as in the arborization pattern of their dendrites in the macroglomerulus. The projection neurons of two other classes each innervate many glomeruli in the antennal lobe, those of one class sending their axons into the protocerebrum in the antenno-cerebral tract IV and the other, in the outer antenno-cerebral tract. The neurons of antenno-cerebral tract IV innervate not only the mushroom body calyces and the lateral lobe but also neuropil regions not previously described in the cockroach. Neurons with axons in the outer antenno-cerebral tract have no terminals in the calyces but innervate the lateral lobe and the neuropil surrounding the tract. The morphological findings presented here show that, in addition to the tracts previously documented in the cockroach brain, there are other, presumably olfactory, connections between the deutocerebrum and the protocerebrum. PMID- 8454729 TI - Goldfish bipolar cells and axon terminal patterns: a Golgi study. AB - The morphology and axon terminal arrangement of Golgi stained goldfish bipolar cells were examined to understand better the organization of bipolar cells in the inner plexiform layer (IPL) of the retina. Fifteen morphological bipolar cell types were identified, representing two major cell classes: mixed input cells that receive input from rod and cone photoreceptors, and cone bipolar cells that receive input from cones only. Mixed input bipolar cells comprised six types, including two new types, characterized by large somas and terminals. The terminals of mixed input bipolar cells terminated strictly within sublamina a or b of the IPL. Cone bipolar cells comprised nine subtypes, including seven new types, characterized by small somas and from one to four small terminal bulbs along the length of the axon, each having a characteristic termination depth in the IPL. The cone bipolar cell system had a complex multilaminar organization of terminals in the IPL, but maintained a high degree of anatomical symmetry about sublamina a and b. Cone bipolar cells could be divided into three groups: cells terminating within sublamina a and having an anatomically symmetrical counterpart terminating in sublamina b; cells with anatomically similar terminals in both sublamina a and b; and cells having no anatomically symmetrical counterpart or having anatomically dissimilar terminals in sublamina a and b. Based on bipolar cell terminal arrangement, we suggest that each bipolar cell type probably has a unique set of synaptic targets in the IPL, and that several bipolar cell types may be involved in functionally equivalent circuits at more than one level in the IPL. PMID- 8454730 TI - The organization of the efferent projections from the pontine parabrachial area to the amygdaloid complex: a Phaseolus vulgaris leucoagglutinin (PHA-L) study in the rat. AB - The organization of the efferent projections from the pontine parabrachial (pPB) area to the amygdala has been studied in the rat by using microinjections of Phaseolus vulgaris leucoagglutinin (PHA-L), a sensitive and selective anterograde axonal marker, into restricted subregions of the pPB area. The results confirmed that the pPB area primarily projected onto the ipsilateral nucleus centralis of the amygdala (Ce), and to a lesser extent onto the ipsilateral posterior basolateral (BLP), anterior basomedial (BMA), and amygdaloid cortical (ACo) nuclei of the amygdala. Substantial projections were also found in the substantia innominata dorsal/ventral portion of the globus pallidus (SId/GPv), substriatal (SStr), and fondus striatal (FStr) regions which continue the amygdala rostrally. The results demonstrated that the projections of the pPB area onto the Ce were topically organized: 1) The region of the pPB area mainly including the medial subnucleus (pPBm), the waist area (pPBwa), and a thin rostral lamina of the ventral lateral subnucleus (pPBvl) projects primarily to the medial portion of the Ce (CeM). Dense projections were also found in the BLP, BMA, and ACo nuclei of the amygdala, and in the SId/GPv, SStr, and FStr rostral areas. 2) The region of the pPB mainly including the rostral portion of the central lateral subnucleus (pPBcl) and the outer-rostral portion of the external lateral subnucleus (pPBel) projects primarily to the lateral portion of the Ce (CeL). 3) The region of the pPB mainly including the dorsolateral subnucleus (pPBdl), the remaining pPBel, and the external medial (pPBem) subnuclei projects primarily to the lateral capsular portion of the Ce (CeLC) and bilaterally to its rostral portion. Dense projections were also found in the regions which extend the CeLC rostrally and in the SId/GPv, SStr, and FStr rostral areas. The possible role of each of the three parabrachio-amygdaloid pathways described is discussed. It was suggested that the pPB-CeM pathway is mainly implicated in gustatory processes; the pPB-CeL pathway is mainly implicated in visceral and chemosensitive processes; and the pPB-CeLC pathway is mainly implicated in respiratory, cardiovascular, and nociceptive processes. PMID- 8454731 TI - Coincidence of Schwann cell-derived basal lamina development and loss of regenerative specificity of spinal motoneurons. AB - The Schwann cell-derived basal lamina forms a tube around single peripheral axons or small groups of axons that is continuous from the spinal cord to the target. In bullfrog tadpoles (Rana catesbeiana), motor axons transected at early developmental stages regenerate to the appropriate hindlimb region. In the present paper, we found that at these stages Schwann tubes are absent by morphological criteria, and individual axons are separated only by occasional extensions of support cells. At stages when axons no longer regenerate to the correct hindlimb region, every axon is encased in a basal lamina tube. Schwann tubes persist in the distal stump after nerve transection, and regenerating axons grow within these tubes. These findings are consistent with previous results showing that the errors regenerating axons make in older animals are not random, but depend upon the course of the denervated Schwann tubes to which they have access. In order to determine whether formation of the Schwann tube itself or interaction of its molecular constituents with growing axons was associated with loss of regenerative specificity, the expression during development of two major constituents of the basal lamina, laminin and heparan sulfate proteoglycan, was investigated. Immunoreactivity to both constituents was present both before and after the transition from specific to nonspecific regeneration, indicating that their expression per se was not sufficient to limit regenerative specificity. These data support the hypothesis that the physical constraint imposed by the Schwann cell-derived basal lamina prevents regenerative specificity. PMID- 8454732 TI - A method for unbiased and efficient estimation of number and mean volume of specified neuron subtypes in rat dorsal root ganglion. AB - By means of unbiased stereological principles and systematic sampling techniques, the number, the mean volume, and the distributions of neuron volumes of the A- and B-cells of the dorsal root ganglion have been estimated. The number of each neuron type was estimated from the product of the volume of the ganglion, obtained with the Cavalieri principle on serial sections of the ganglion, and the numerical density, obtained with optical dissectors on the same sections. The mean volume of the cell bodies of each type was estimated by applying the nucleator technique to the neurons sampled with the optical dissectors. The precision of the estimate in each animal was evaluated on the basis of the variation between animals. An optimal sampling scheme is described by which estimates of the total number, the mean volume, and the distribution of cell body volumes can be obtained in about 8 hours. In the right fifth lumbar dorsal root ganglion taken from four mature, male Wistar rats, the mean total number of neurons was found to be 17,900. Of these, 28% were A-cells, with a mean cell body volume of 53,400 microns3, and 70% were B-cells, with a mean cell body volume of 8,540 microns3. There was a considerable overlap between the volume distributions of the two cell types. PMID- 8454733 TI - Dendritic remodelling of retinal ganglion cells during development of the rat. AB - Investigation of the morphology of ganglion cells in the cat retina has shown that a remarkable reduction in the number of dendritic spines and branches occurs during development of the alpha and beta cell classes. To learn whether dendritic remodelling represents a generalized mechanism of mammalian retinal ganglion cell development, we have examined the morphology of ganglion cells in the retina of the developing rat. The present study has concentrated on type II cells, which retain a great number of dendritic spines and branches in the adult and comprise a large proportion of the population of rat retinal ganglion cells. To reveal fine dendritic and axonal processes, Lucifer yellow was injected intracellularly in living retinae maintained in vitro. Size and complexity of the dendritic trees were found to increase rapidly during an initial stage of development lasting from late fetal life until approximately postnatal day 12 (P12). Dendrites and axons of immature ganglion cells expressed several transient morphological features comprising an excessive number of dendritic branches and spine-like processes, and short, delicate axonal sidebranches. The following developmental stage was characterized by a remarkable decrease in the morphological complexity of retinal ganglion cells and a slowed growth of their dendritic fields. The number of dendritic branches and spines of types I and II retinal ganglion cells declined after P12 to reach a mature level by the end of the first postnatal month. Thus, even cells that retain a highly complex dendritic tree into the adult state undergo extensive remodelling. These results suggest that regressive modifications at the level of the dendritic field constitute a generalized mechanism of maturation in mammalian retinal ganglion cells. PMID- 8454734 TI - Distribution of [3H]QNB and [125I]alpha-bungarotoxin binding and acetylcholinesterase activity in visual system and hippocampal structures of eleven mammalian species. AB - This study assessed interspecies differences in regional brain distribution of [3H]QNB binding, [125I]alpha-bungarotoxin binding and acetylcholinesterase activity, by autoradiographic and histochemical methods. Eleven mammalian species were examined, including carnivores (cat, dog), a lagomorph (rabbit), and rodents (squirrel, guinea pig, gerbil, hamster, vole, lemming, rat, mouse). Comparisons were based on primary visual system structures (superior colliculus, lateral geniculate nucleus, primary visual cortex) and the hippocampal formation. The two radioligands differed greatly in the degree of interspecies variation: while the pattern of [3H]QNB binding was quite similar across species, [125I]alpha bungarotoxin showed striking interspecies diversity. This contrast was most obvious in laminar patterns of the visual cortex and hippocampal formation. Regional distributions of acetylcholinesterase staining were fairly diverse, and were unlike the patterns of either [3H]QNB or [125I]alpha-bungarotoxin. The two ligands showed more consistency in overall levels across species than did acetylcholinesterase. Possible correlates of the differences in interspecies diversity are discussed. PMID- 8454735 TI - Codistribution of GABA- with acetylcholine-synthesizing neurons in the basal forebrain of the rat. AB - In recent years, GABAergic neurons have been identified in the basal forebrain where cholinergic cortically projecting neurons are located and known to be important in mechanisms of cortical activation. In the present study in the rat, the relationship of the GABA-synthesizing neurons to the acetylcholine synthesizing neurons was examined by application of a sequential double staining immunohistochemical procedure involving the peroxidase-antiperoxidase technique for glutamic acid decarboxylase (GAD) and choline acetyltransferase (ChAT). In these double and adjacent single immunostained series of sections, the GAD+ and ChAT+ cells were mapped, counted and measured with the aid of a computerized image analysis system. Through the entire basal forebrain, there was no evidence for colocalization of GAD and ChAT in the same neurons. Instead, a large population of GAD-immunoreactive neurons is codistributed with ChAT immunoreactive neurons and outnumbers them by a factor of two: approximately 39,000 GAD+ cells to 18,000 ChAT+ cells. Although the GAD+ and ChAT+ neurons lie intermingled within fascicles of the major longitudinal and transverse forebrain fiber systems in subregions of the basal forebrain, the GAD+ cells are more highly concentrated within different sectors of the pathways and regions than the ChAT+ cells. Although GAD+ neurons resemble ChAT+ neurons in certain regions, both being bi- or multipolar and, on average, medium-sized cells, the GAD+ neurons are, in the majority (51%), small-sized cells (< 15 microns in length) and as a population significantly smaller than the ChAT+ neurons. These results suggest that many GABAergic neurons may represent interneurons in the basal forebrain and potentially exert an inhibitory influence on adjacent cortically projecting cholinergic neurons. Medium- to large GAD+ cells, which resemble similar ChAT+ cells, are also present and represent the majority of the GAD+ cells in the nucleus of the diagonal band of Broca, magnocellular preoptic nucleus, and olfactory tubercle, but represent the minority in the anterior and posterior substantia innominata and globus pallidus. Given their prominent size, such GABAergic cells may also exert an inhibitory influence outside the basal forebrain as projection neurons and potentially in parallel with cholinergic neurons, to certain regions of the cerebral cortex. Accordingly, GABAergic cells may be considered as constituents of the magnocellular basal nucleus and potentially important elements within the ventral extrathalamic relay from the brainstem reticular formation to the cerebral cortex. PMID- 8454736 TI - Morphology of neurons in the thalamic reticular nucleus (TRN) of mammals as revealed by intracellular injections into fixed brain slices. AB - I have investigated the morphology of neurons in the thalamic reticular nucleus (TRN) by means of intracellular injections in fixed tissue in order to study whether neurons in visual (dorsocaudal part), somatosensory (intermediate part), or limbic/motor (rostral part) sectors in the rat, rabbit, and cat differ morphologically in relation to their different sensory cortical or thalamic inputs. In addition, I have compared the different mammalian species to ask whether there is a morphological difference of TRN neurons according to reported differences in the intrinsic thalamic organisation, for example, due to the presence of GABAergic local circuit neurons in the majority of thalamic nuclei in the cat and the lack of those neurons in most of the rat thalamic nuclei, and presynaptic dendrites in the cat but not in the rat. In all animals investigated so far, neurons in the caudal (visual) and intermediate (somatosensory) part of the TRN have an elongated dendritic morphology in all three species, but some neurons in the rostral part, in particular in dorsal sections, have a distinctive multipolar morphology. Neurons have round, ovoid, or elongated somata ranging in area between 150 and 860 microns 2. In general, 4-8 first order dendrites emerge directly from the two poles of the soma or from a thick stem segment. Most of the dendrites then run parallel to the borders of the nucleus extending for relatively long distances, up to 450 microns, but remain inside the border of the nucleus. Only a few (1-3) dendrites could be observed to run perpendicular to the border of the nucleus and generally only for a short distance (20-70 microns). Some of the smooth first order dendrites give rise to second order dendrites (up to 200 microns in length), which then branch into short (15-70 microns) third order dendrites. Dendritic spines and varicosities, spine-like protusions and/or hair-like processes are mainly found on second and third order dendrites. Surprisingly, the shape, arrangement, and the size of the dendritic field are not strictly related to the shape and size of the nucleus. In mammalian species with a comparatively narrow TRN (rat and cat) the dendritic field size was similar to that in the rabbit with a broad TRN. There was considerable variability in dendritic morphology in the caudal and intermediate parts of TRN. However, in contrast to two recent studies in the rat TRN I have found no obvious basis for classification of neurons in the mammalian TRN according to dendritic morphology.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8454737 TI - Morphology and somatotopy of the central arborizations of rapidly adapting glabrous skin afferents in the rat lumbar spinal cord. AB - The central arborizations in the dorsal horn of the spinal cord of 23 rapidly adapting (RA) A-beta primary afferent neurons innervating different regions of the glabrous skin of the hindpaw were studied by the intra-axonal injection of horseradish peroxidase in adult rats. A total of 284 arbors of the complex, simple, and blind-ending variety were recovered. The arbors of RA afferents innervating the toes, paw pads, and non-pad hindpaw differed from each other in branch pattern and dimensions. The simple and complex arbors, which are both bouton-containing, were distributed mainly in laminae III-V, although some complex arbors projected dorsally into lamina IIi. The hindpaw glabrous skin afferent terminals were located in the lumbar enlargement from caudal L3 to rostral L6. A crude somatotopic organization was observed such that toes 1-5 were represented successively in more caudal positions from mid-L4 to caudal L5. The paw pads were organized in a rostrocaudal sequence moving from the paw pads proximal to toe 1 across the foot to the paw pads proximal to toe 5, from caudal L3 to mid-L5. Non-pad hindpaw afferents were located in caudal L5. Overlap between toe, paw pad and non-pad afferent central fields was present, however, and the central terminals of afferents with non-adjacent peripheral receptive fields were shown to occupy the same region of the dorsal horn. PMID- 8454738 TI - Differential expression of neuron-glia cell adhesion molecule (Ng-CAM) on developing axons and growth cones of interneurons in the chick embryo spinal cord: an immunoelectron microscopic study. AB - To elucidate the role of neuron-glia cell adhesion molecule (Ng-CAM) in axonal pathway formation of avian spinal interneurons, we have examined the ultrastructural expression of Ng-CAM in the developing spinal cord, by using a preembedding immunocytochemical method. Ng-CAM immunoreactivity was punctate and was restricted to cell surfaces. In accordance with our previous light microscopic observations (Shiga et al., '90), the earliest developing spinal interneurons were Ng-CAM-positive on their cell bodies, axons, and growth cones. Axons and growth cones that were either fasciculated or in contact with each other strongly expressed Ng-CAM, thus indicating the possible involvement of Ng CAM in fasciculation of axons and in the contact guidance of growth cones along preexisting axons. By using higher resolution immunoelectron microscopy, the present study has also revealed new information on the subcellular localization of Ng-CAM on developing spinal interneurons, neuroepithelial cells, and floor plate cells. Although Ng-CAM immunoreactivity was prominent on both axons and growth cones, these structures were Ng-CAM-negative when they contacted the basal lamina around the spinal cord. By contrast, Ng-CAM was detectable on the surface of both neuroepithelial cells and floor plate cells only when they made contact with the Ng-CAM-positive axons and growth cones of interneurons. These results suggest that the subcellular distribution of Ng-CAM is regulated differentially, depending on the apposing cell surfaces, and that such differential and developmentally regulated expression may contribute to the elongation, fasciculation, and guidance of spinal axons. PMID- 8454739 TI - Segmental arrangement of reticulospinal neurons in the goldfish hindbrain. AB - The hindbrain is evolutionarily conserved among diverse vertebrate phyla. In vertebrate embryos, the hindbrain is segmentally organized as a series of overt swellings known as rhombomeres. In the larval zebrafish Brachydanio rerio, conspicuous and identifiable reticulospinal neurons are positioned in the center of rhombomeres. Segmentally homologous reticulospinal neurons that share a range of morphological, developmental, and biochemical features occupy adjacent rhombomeres. We have recently shown that reticulospinal neurons of the zebrafish survive ontogeny without considerable morphological modification and we suggested that homologous neurons may share similar functions at different stages of development (Lee and Eaton: Journal of Comparative Neurology 304:34-52, 1991). The goldfish Carassius auratus, a related cyprinid, is especially suited for neurophysiological and behavioral studies. However, it is not yet known if the various reticulospinal neurons of zebrafish are generalizable to other species such as the goldfish. Therefore, we sought to examine the extent to which reticulospinal neurons of the zebrafish are also present in the adult goldfish. Analysis of 45 brains retrogradely labeled with horseradish peroxidase (HRP) from the spinal cord showed that reticulospinal neurons are arranged as a series of seven segments within the hindbrain; a regular interval of approximately 200 microns separates adjacent segments. Although the goldfish reticulospinal system has more neurons than the zebrafish, many reticulospinal neuron types continue to be identifiable. Moreover, comparisons of dendritic arborizations and axon paths between the two species showed that the morphology between various neuron types is virtually identical. The cross-taxonomic similarities between the reticulospinal systems of these related cyprinids make it possible to pursue functional considerations of segmentally homologous neurons in the goldfish hindbrain. PMID- 8454740 TI - William H. Oldendorf, M.D. (1925-1992). PMID- 8454741 TI - 3D phase contrast MRI of cerebral blood flow and surface anatomy. AB - Noninvasive MR acquisition of blood flow and stationary tissue provides three dimensional display of flow and of the vascular and brain surfaces. The calculated motion of a simulated bolus injection is derived from the measured velocity vector field and is animated to resemble cine angiography. Simulation of a bolus injection into the basilar artery of a healthy volunteer shows the blood flow into the posterior cerebral arteries. PMID- 8454742 TI - Selective MR angiography and intracranial collateral blood flow. AB - This study evaluates the usefulness of MR angiography (MRA) in analyzing the individual collateral flow dynamics and anatomy of the circle of Willis in patients with high-grade extracranial carotid stenosis or occlusion. Selective MRA of the carotid or vertebrobasilar territory was performed by means of presaturation of up to three of the brain-supplying arteries at the level of the middle or lower neck (angled presaturation slabs). Results obtained with selective and nonselective arterial MRA in 45 consecutive patients were compared with findings at transcranial Doppler ultrasonography and intraarterial angiography, the latter serving as the "gold standard." Sensitivity of selective MRA in detecting intracranial collateral circulation via the anterior and posterior communicating artery was 95 and 97%, respectively; sensitivity in depicting extracranial to intracranial transorbital flow was lower (67%). Nonselective arterial MRA was 100% sensitive in detecting a nonfilling of the horizontal (A1) segment of the anterior cerebral artery and in identifying an origin of the posterior cerebral artery from the intracranial carotid artery. Visibility of the posterior communicating artery at MRA predicted for pathological collateral flow via this vessel in all cases. We conclude that selective and nonselective MRA of the cerebral arteries as used here is the most powerful noninvasive method to demonstrate collateral circulation via the basal communicating arteries and to identify hemodynamically relevant anatomic variants of the circle of Willis. PMID- 8454743 TI - 3D TOF MR angiography of cerebral arteriovenous malformations after radiosurgery. AB - To investigate the potential of three-dimensional time-of-flight MR angiography (MRA) to complement SE imaging, 18 patients with intracerebral arteriovenous malformations were prospectively followed after undergoing radiosurgery. Vessel occlusion after stereotaxic single high dose radiotherapy develops slowly. The MRA detected signs of nidus obliteration earlier and with a higher sensitivity than did SE imaging. Six months after radiosurgery, MRA showed a reduction of the nidus flow signals in nine patients and after 1 year it showed reduction in 15 of the 18 patients. As shown by MRA, the loss of flow signals was related to a reduction of the nidus size in 4 patients after 6 months and in 11 after 1 year. The SE imaging revealed a reduction of the nidus size in only two patients after 6 months and in eight after 1 year. The signal intensity of the feeding arteries was reduced in nine patients and that of the draining veins was reduced in six. The T2-weighted images exhibited white matter lesions in eight patients after 1 year. For complete follow-up, SE imaging should be performed together with MRA. PMID- 8454744 TI - Absolute quantitation of short TE brain 1H-MR spectra and spectroscopic imaging data. AB - A method for determining the concentrations of the materials that produce the well-resolved singlet signals in short TE brain 1H MR spectroscopic examinations is presented. Concentration determination is achieved by a water-referencing procedure. The ratios of the areas of the choline, total creatine, and N-acetyl signals to that of the water signal from the same volume of interest (VOI) are determined using acquisitions with and without water suppression. The tissue concentrations of the molecules producing the three signals can then be determined if the water concentration in the VOI can be found. This is done with a density-weighted MR study. The MR study provides the ratio of the mean MR signal amplitude from the VOI to that from an external standard containing a known water concentration. The method's flexibility is illustrated by using it with two different single-volume localization schemes and spectroscopic imaging. Preliminary evaluations of accuracy and reproducibility are made in phantom, animal, and limited human studies. The method's advantages and limitations are discussed. PMID- 8454745 TI - Accuracy and reproducibility in volumetric analysis of multiple sclerosis lesions. AB - The accuracy and reproducibility of dual-contrast segmentation based on nonparametric feature map analysis have been investigated in a multicomponent gelatin phantom. The root mean square errors in volume ranged from 0.02 cm3 for small volumes to 3.8 cm3 for larger volumes, with a mean error of 0.97 cm3. Average inter- and intraobserver coefficients of variation were found to be < 7% for all compartments. To evaluate the reproducibility of segmentation of clinical image data, volumes of total brain, CSF, and multiple sclerosis (MS) lesions were obtained from five image sets of MS patients. Inter- and intraobserver coefficients of variations were computed for the patient data and were found to be < 5% for brain, 17% for CSF, and 20% for MS lesions. Such variations were found to be reduced by appropriate preprocessing of the images. PMID- 8454746 TI - MRI of amygdala and hippocampus in temporal lobe epilepsy. AB - In this study we compared the results of qualitative visual analysis of MRI with volumetric studies of the amygdala (AM) and hippocampal formation (HF) in a group of 31 patients. Twenty-six patients with temporal lobe epilepsy (TLE) and six with non-TLE had MRI studies using a 1.5 T Gyroscan following a specific protocol for scan acquisition. The MR images were interpreted by two blinded radiologists and by a third if discrepancy arose. Volumetric studies were carried out by one or two raters. The volumetric measurements of AM and HF were accurate in lateralizing the epileptogenic area in patients with TLE, concordant with the EEG in 92%; there was no false lateralization. In those patients who underwent surgery, there was a correlation between the degree of mesial temporal sclerosis demonstrated by histopathology, the amount of volume reduction, and the asymmetry. In patients with non-TLE, there was no volume asymmetry of AM or HF. The MR qualitative assessment yielded positive lateralization in patients with TLE in 56%, conflicting lateralization in 20%, and lateralization contralateral to the focus in 12%. A hyperintense signal in mesial structures was found ipsilateral to the focus in 40% and contralateral in 12% of patients with TLE. Volumetric study improves the diagnostic yield of MRI evaluation in patients with TLE not related to gross structural lesions. The interrater variability is low and the data are accurate and reproducible. Because they are quantitative, volumetric studies permit better comparison of results in different subgroups of patients with TLE. PMID- 8454747 TI - MRI and clinical findings in rhombencephalosynapsis. AB - Rhombencephalosynapsis is an unusual disorder characterized predominantly by agenesis/hypogenesis of the cerebellar vermis and fusion of the cerebellar hemispheres. Three cases are reported with emphasis on the MRI and clinical findings. Discussion of the relative importance of the cerebellar anomalies and associated supratentorial abnormalities is included. PMID- 8454749 TI - Elastically deforming 3D atlas to match anatomical brain images. AB - To evaluate our system for elastically deforming a three-dimensional atlas to match anatomical brain images, six deformed versions of an atlas were generated. The deformed atlases were created by elastically mapping an anatomical brain atlas onto different MR brain image volumes. The mapping matches the edges of the ventricles and the surface of the brain; the resultant deformations are propagated through the atlas volume, deforming the remainder of the structures in the process. The atlas was then elastically matched to its deformed versions. The accuracy of the resultant matches was evaluated by determining the correspondence of 32 cortical and subcortical structures. The system on average matched the centroid of a structure to within 1 mm of its true position and fit a structure to within 11% of its true volume. The overlap between the matched and true structures, defined by the ratio between the volume of their intersection and the volume of their union, averaged 66%. When the gray-white interface was included for matching, the mean overlap improved to 78%; each structure was matched to within 0.6 mm of its true position and fit to within 6% of its true volume. Preliminary studies were also made to determine the effect of the compliance of the atlas on the resultant match. PMID- 8454748 TI - Klippel-Feil syndrome: CT and MR of acquired and congenital abnormalities of cervical spine and cord. AB - We reviewed MR and CT myelographic studies in patients with the Klippel-Feil syndrome (KFS) to determine the patterns of associated congenital and acquired abnormalities of the spine and spinal cord and to correlate these radiologic findings with the manner of clinical presentation. Twenty-four consecutive patients with radiologically definite KFS were evaluated by a cross-sectional imaging technique (CT or MR) over a 6 year period. Radiologic images were blindly interpreted by a panel of three experienced neuroradiologists and then correlated with clinical history. Cervical spondylosis or disk herniations were the most common radiologic abnormalities encountered, seen in 10 (42%) of the 24 patients. While some clustering of these secondary degenerative changes occurred at levels immediately adjacent to the fused vertebrae, in most patients spondylotic changes were seen widely distributed throughout the lower cervical region. Coexisting congenital defects of the spinal cord or brain were encountered in seven patients, six of whom were female, consisting of cervical cord dysraphism or diastematomyelia (n = 5) and Chiari I malformations (n = 2). In only eight patients (33%) had the diagnosis of KFS been suspected clinically prior to imaging by the presence of short neck, limited cervical mobility, or low occipital hairline. In the remaining 16 patients, mostly adolescents or adults being evaluated for cervical sensory or motor syndromes, the diagnosis of KFS was made radiologically at the time of the imaging referral. PMID- 8454750 TI - Assessing human cardiac allograft rejection using MRI with Gd-DOTA. AB - To explore the potential role of MRI in detecting cardiac allograft rejection in transplant recipients using gadolinium tetraazacyclododecane tetraacetic acid (Gd DOTA) for contrast enhancement, we examined 7 normal healthy volunteers and 39 patients separated into three groups according to histological findings. Quantitative myocardial enhancement (ME), expressed as the ratio of maximum signal intensity after intravenous Gd-DOTA injection to signal intensity before intravenous injection of Gd-DOTA, was significantly lower for patients without histological rejection (n = 14; regional ME = 83 +/- 41%; mean ME = 53 +/- 24%) when compared with patients with grade 1 histological rejection (n = 18; regional ME = 122 +/- 20%, p = 0.02; mean ME = 70 +/- 14%, p < 0.05) and with patients with grade 2 or 3 rejection (n = 7; regional ME = 135 +/- 44%, p = 0.02; mean ME = 81 +/- 27%, p < 0.05). Myocardial enhancement was not significantly different in patients with grade 1 histological rejection compared with patients with grade 2 or 3 rejection. Because predominant focal areas of ME were observed in all patients, regional ME seemed a better measurement than mean ME to distinguish focal histological changes when the rejection process is beginning. More sophisticated software analysis is necessary to quantify and map high ME to establish the exact relationship between the extent of edema and the severity of rejection. PMID- 8454751 TI - Right ventricular diastolic filling: evaluation with velocity-encoded cine MRI. AB - Abnormal flow velocity curves across the tricuspid valve (TV) and in the superior vena cava have been described in patients with abnormal right ventricular (RV) relaxation or restriction and with pericardial diseases by means of Doppler echocardiography. In this study, various imaging planes and strategies of velocity-encoded cine (VEC) MR for measurement of peak E and peak A velocities and the E/A ratio across the TV were evaluated and compared to Doppler measurements in 10 normal volunteers. In addition, VEC-MR velocity measurements were performed in the superior vena cava. Peak E and peak A velocities derived from three-dimensional VEC-MR phase images were slightly higher than velocities derived from two-dimensional VEC images. Higher velocities were measured by VEC MR in the vertical long-axis plane compared with the horizontal long-axis plane. Excellent correlations (r > 0.89) were found between E/A ratios derived by VEC-MR and Doppler echocardiography. The interobserver variability for VEC-MR measurements was in the range of 2%. The VEC-MR depicted normal superior vena cava velocity curves in every volunteer. These results indicate that VEC-MR may offer a highly reproducible means of assessing abnormal filling properties of the RV. PMID- 8454753 TI - Tuberculosis of the chest wall: CT findings. AB - To assess the CT features of tuberculosis of the chest wall, the CT findings in four patients with documented tuberculous chest wall infection were reviewed. Two patients were Caucasian and two were of Chinese origin. All had normal immune status. In two cases tuberculosis involved the ribs, in one the costal cartilage, and in one the sternoclavicular joint. Computed tomography demonstrated osseous and cartilaginous destruction (in four), soft tissue masses with calcification (in two), and rim enhancement following intravenous contrast medium administration (in two). Underlying pleuroparenchymal tuberculosis was present in two cases. Tuberculosis of the chest wall is characterized by bone or costal cartilage destruction and soft tissue masses that may demonstrate calcification or rim enhancement with or without evidence of underlying lung or pleural disease. PMID- 8454752 TI - MRI of bronchogenic cysts. AB - The MR appearance of eight bronchogenic cysts is reported. All the cysts appeared homogeneous and were of very high signal intensity, approximating that of CSF on spin-echo T2-weighted imaging, and of relatively high intensity, between that of muscle and subcutaneous fat on T1-weighted imaging. The cysts were round or ovoid and were well demarcated. These findings are consistent with the fluid-containing properties of cysts. PMID- 8454754 TI - Malignant schwannomas of the thorax: CT findings. AB - We reviewed CT of eight patients with malignant schwannomas arising in the thorax. Only one patient had neurofibromatosis. Five lesions occurred in the posterior mediastinum, one lesion was in the middle mediastinum, and two lesions were in the chest wall. Common CT findings were the presence of low-density areas (six of eight), compression of adjacent structures (six of eight), pleural abnormalities (six of eight), such as pleural effusion or pleural nodules, and metastatic pulmonary nodules (five of eight). Pleural abnormalities or pulmonary nodules were detected in seven of eight patients. These CT findings can help in differentiating malignant schwannoma from benign neurogenic tumor. PMID- 8454755 TI - Early MR follow-up of partial hepatectomy. AB - Twenty-seven patients were studied with MRI between 3 and 40 days following partial liver resection. Twenty-four patients had undergone major hepatectomy (three to six segments) and three had undergone minor hepatectomy (tumorectomy, one; bisegmentectomy, two). Indications for surgery were as follows: metastases (n = 16), hepatocellular carcinoma (n = 5), hemangioma (n = 3), focal nodular hyperplasia (n = 2), and cholangiocarcinoma (n = 1). A total of 36 MR examinations were performed using a 1.5 T superconducting unit. Three patients were studied three times and three patients were studied twice. The MR images were evaluated to detect and to characterize liver parenchymal abnormalities and intraabdominal fluid or blood collections as well as to assess vascular and/or graft patency. The MR images showed hepatic ischemia in two cases and allowed differentiation between intraabdominal hemorrhagic (n = 30 and nonhemorrhagic (n = 4) fluid collections. Gradient echo images allowed assessment of polytetrafluoroethylene graft patency as well as demonstration of iliac vein (one case) and portal vein (one case) thrombosis. The presence of surgical clips at the resection margins did not affect image quality. PMID- 8454756 TI - Acute cholangitis: CT evaluation. AB - The CT findings of 23 patients with proven acute ascending cholangitis were retrospectively evaluated. Computed tomography confirmed the clinical diagnosis and detected the site and etiology of the obstructive process in the majority of patients. Biliary dilatation consistent with the clinical suspicion of acute cholangitis was present in 18 patients (78%), the level of the obstruction was detected in 15 patients, and the etiology of the obstructive process was visualized in 14 cases. Five patients presented with air in the biliary tree and three patients had liver abscesses. There was no good correlation established between jaundice, biliary infection, and the presence or degree of biliary dilatation. Biliary obstruction and acute cholangitis can develop before biliary dilatation is detected. In addition, CT showed limitations in establishing the etiology of the obstructive process, particularly in failing to detect 7 of 17 cases of cholesterol biliary stones. PMID- 8454757 TI - Mn-DPDP enhanced MRI in experimental bile duct obstruction. AB - To assess both the effect of Mn-DPDP as a hepatobiliary-specific contrast agent in bile duct obstruction and the relative role of liver and kidney in the elimination of this agent from the body, an animal experiment was set up. Twelve rats were used and divided into three groups. In group 1 the common bile duct was ligated, in group 2 bile duct ligation was limited to one lobe, and group 3 served as control. Magnetic resonance T1-weighted SE images were obtained before and after the injection of 25 mumol/kg of Mn-DPDP during the first 2 h and at day 1, 2, 3, 4, and, in some animals, up to 21 days. In normal rats the absolute enhancement signal-to-noise ratio (S/N) versus time plots obtained from the liver after Mn-DPDP injection returned to precontrast values within 24 h. In the group with common bile duct ligation, important liver enhancement persisted up to 21 days. In the group with selective obstruction, liver intensity normalized after 3 days. The S/N plots from spleen, renal cortex, and obstructed liver lobe showed similarities in time course. The present data indicate that Mn elimination is strongly impaired in the presence of bile duct obstruction. Renal glomerular filtration is ineffective in eliminating Mn from the body. The persisting splenic and renal cortical enhancement suggests that free Mn or some Mn-DPDP metabolite either is strongly bound to plasma proteins and acts as a blood pooling agent and/or is uptaken by the splenic or renal parenchyma. PMID- 8454758 TI - MR features of bleeding renal arteriovenous fistulae. AB - The MR findings of two patients with bleeding renal arteriovenous fistulae are presented. In each case MR demonstrated a perinephric hemorrhage in association with the distinctive finding of a discrete focal intraparenchymal hematoma. PMID- 8454759 TI - Popliteal artery pseudoaneurysm in a patient with hereditary multiple exostoses: MRI and MRA diagnosis. PMID- 8454760 TI - MRI of suprascapular neuropathy in a weight lifter. AB - Suprascapular neuropathy results from abnormal compression of the suprascapular nerve, typically at the suprascapular or spinoglenoid notch. This may be produced by either mass effect such as ganglion cyst or by certain repetitive shoulder motions producing wide scapular excursion (e.g., hyperabduction), which causes traction upon the nerve. Certain sports activities such as weight lifting predispose to this type of neuropathy. The clinical presentation is frequently not specific and the patient may be sent for MR evaluation to rule out rotator cuff tear or other more common shoulder abnormalities. This entity should be suspected if MR images demonstrate selective atrophy of the spinatus muscles with a structurally intact rotator cuff. PMID- 8454761 TI - CT of superior mesenteric vein thrombosis complicating periappendiceal abscess. AB - Acute mesenteric vein thrombosis is a rare complication of appendicitis. In this report we describe the clinical association of these entities and emphasize how early diagnosis by CT can expedite treatment. PMID- 8454762 TI - Leptomeningeal gliomatosis: MR findings. AB - We report a case of primary diffuse leptomeningeal gliomatosis documented by MR. The radiological findings guided the surgical biopsy toward the area involved. Pathological examination confirmed the diagnosis. The patient could consequently benefit from treatment, i.e., radiation therapy, which was followed by clinical relief. PMID- 8454763 TI - Gadolinium enhancement in the center of a spinal epidural hematoma in a hemophiliac. AB - Spinal epidural hematoma (SEH) is an uncommon complication of hemophilia. It is a neurologic and neurosurgical emergency and prompt diagnosis is imperative. The utility of MRI in the diagnosis of hemorrhage is well established. We present a case of an SEH in a hemophiliac patient that demonstrated gadolinium enhancement. PMID- 8454764 TI - Riedel thyroiditis: US, CT, and MR evaluation. AB - We report the ultrasound, CT, and MR findings in a patient with Riedel thyroiditis. The hypointensity of the lesion observed on T1- and T2-weighted sequences, especially when associated with infiltration of adjacent structures of the neck, can be suggestive of Riedel thyroiditis. PMID- 8454765 TI - Gerstmann-Straussler-Scheinker syndrome: MR findings. PMID- 8454766 TI - Reduction of artifacts from breathing and peristalsis in phase-contrast MRA of the chest and abdomen. AB - Strategies for the acquisition of temporally resolved phase-contrast angiography are described and demonstrated. Projections are acquired through the entire thickness of the subject permitting excitation geometries to be independent of image orientation. Minimal delays are used between the acquisition of oppositely flow-encoded data resulting in fewer artifacts from movement of nominally stationary tissue. A protocol that suppresses artifacts from both peristalsis and breathing is presented for the aortic arch and iliac arteries. PMID- 8454768 TI - International Association for Dental Research, divisional abstracts. PMID- 8454769 TI - Dental education and the 21st century. PMID- 8454767 TI - Combined MRI and MRA for limb salvage planning. AB - Magnetic resonance angiography (MRA) was performed in two patients with primary bone neoplasms being staged for differing types of limb-salvage procedures. A gated two-dimensional (2D) phase contrast MRA sequence that is capable of variable velocity encoding throughout the cardiac cycle was used to acquire the MRA images. The resulting cardiac phase images were added with a matched filter algorithm to create a single high signal-to-noise ratio image. An SE MR image in the same plane and field of view was then added to the MRA image. This displayed the relationship of vascular and stationary tissues within a composite picture: a "2D combined angiographic-stationary tissue" image. The anatomy represented gave information equivalent to conventional angiography. While this technique is not an ideal 3D rendering, it is easier to use. Along with other SE sequences acquired as needed for staging, it provides a complete preoperative evaluation of a tumor bed or donor site for a vascularized graft harvest. PMID- 8454770 TI - Primary care dentistry and the primary care agenda. PMID- 8454771 TI - Where to next? The issues in dentistry from the perspective of a dental educator. PMID- 8454772 TI - Perceptions on accreditation and licensure. PMID- 8454773 TI - The future--reaching for the stars. PMID- 8454775 TI - The costs of dental education. PMID- 8454774 TI - Licensure. PMID- 8454776 TI - Accreditation. PMID- 8454777 TI - Perceived sources of stress in the dental school environment. AB - The purpose of this study was to identify the perceived stress of dental students across the entire curriculum (D1-D4 years). The dental environmental stress (DES) questionnaire was administered to 244 (90.4 percent) dental students during 1990. Significant differences were found for 12 questionnaire items across four classes. For male-female comparisons, significant differences were found for 17 questionnaire items, all perceived as more stressful by females; and between classes, significant differences were accounted for by three questionnaire items. Comparisons with previous dental students (1980s) on the identical questionnaire were noted. PMID- 8454778 TI - Behavior management techniques in predoctoral and postdoctoral pediatric dentistry programs. AB - This study surveyed predoctoral and postdoctoral pediatric dental programs, to determine what behavior management techniques are being taught. The expected didactic and clinical proficiency levels were determined for behavior management techniques in four categories: sedation, restraint, parental presence, and communicative behavior management. Postdoctoral programs expect clinical proficiency in most of the 20 selected management techniques while predoctoral programs expect clinical basic competency in some techniques and do not teach others. Both program levels emphasize communicative behavior management techniques. A high percentage of both programs anticipate no change in the teaching of most of the 20 selected techniques. For both types of programs, less emphasis or elimination of "hand-over-mouth" techniques but more emphasis on parental presence for the introductory visit, using positive reinforcement, and using age-appropriate language and descriptions is anticipated. The two most influential factors affecting these anticipated changes were parental preference and changing standards in pediatric dentistry. PMID- 8454779 TI - Student evaluation in the comprehensive care setting. PMID- 8454780 TI - A baseline study of behavioral science instruction in dental schools. PMID- 8454781 TI - Data update. PMID- 8454782 TI - Curriculum guidelines for endodontics. Section on Endodontics of the American Association of Dental Schools. PMID- 8454783 TI - Curriculum guidelines for physiology. Section on Physiology of the American Association of Dental Schools. PMID- 8454784 TI - Granulomatous dermatitis to iron oxide after permanent pigmentation of the eyebrows. AB - BACKGROUND: Tattooing with iron oxide pigment is used to create a permanent line along the eyelid margins and to cause permanent pigmentation of the eyebrows. However inflammatory sequelae can occur. OBJECTIVE: To present the development and treatment of a granulomatous inflammation as a sequela of iron oxide tattooing in the eyebrows. METHOD: A skin biopsy was performed, Histopathologic examination revealed deposits of reddish-brown pigment and a superficial dermal infiltrate consisting of lymphocytes and giant multinucleated cells (Langhan's and foreign body). RESULTS: A patient developed a granulomatous reaction to iron oxide after undergoing permanent pigmentation of the eyebrows. Treatment with systemic and topical steroids resulted in marked improvement at 6-month follow up. CONCLUSIONS: This is an unusual complication. A skin test should be performed on any patient who is to undergo tattooing with iron oxide pigment. PMID- 8454785 TI - Bowenoid changes in Kaposi's sarcoma. AB - BACKGROUND: Previous reports have documented the coexistence of multiple infectious organisms or Kaposi's sarcoma within the same biopsy specimens of mucocutaneous lesions in human immunodeficiency virus- (HIV) infected patients. OBJECTIVE: A 31-year-old black man with the acquired immunodeficiency syndrome (AIDS) who had Bowenoid changes and Kaposi's sarcoma within the same cutaneous lesion is described. METHODS: Microbiologic cultures, microscopic examination, and polymerase chain reaction were performed on a lesional skin biopsy specimen to evaluate for infectious organisms, histopathology, and the presence of human papillomavirus (HPV) deoxyribonucleic acid (DNA), respectively. RESULTS: Bacteria, fungi, and mycobacteria were not detected with special stains and cultures. The histologic findings were consistent with Bowen's disease in the epidermis and patch stage Kaposi's sarcoma in the dermis. There was no polymerase chain reaction product generated from the HPV-specific primers in two individual polymerase chain reaction assays. CONCLUSION: The possibility that coexisting infectious or neoplastic disorders, or both, may be present within a single mucocutaneous lesion should always be considered when evaluating a lesion from an HIV seropositive individual. PMID- 8454786 TI - The running locked intradermal suture. A cosmetically elegant continuous suture for wounds under light tension. AB - A new suture technique, the running locked intradermal suture, is introduced. The suture is continuous and buried, and is designed for closing simple elliptical wounds under light tension in which a good cosmetic result is desired. It is used in conjunction with a topical antibiotic and a transparent dressing. This technique reduces the dermal dead space, achieves close approximation of the epidermal wound edges, has a good cosmetic appearance soon after surgery, reduces necessary postoperative wound care, reduces the risk of wound infection in clean surgical wounds, and obviates suture removal. Three examples of its application on the face are presented. It is compared with frequently used standard wound closure methods are discussed. PMID- 8454787 TI - The influence of age and patient positioning on skin tension lines. AB - BACKGROUND: The best cosmetic results are obtained if certain "skin lines" are followed. However, which "skin lines" are the correct ones has been controversial. OBJECTIVE: To review the history of skin lines, the physiological basis of skin tension lines, and the factors that govern them. METHODS: Twenty seven individuals were observed, 15 greater than 65 years of age, and 12 less than 30 years of age. Patients were placed at 0 degrees and 90 degrees and the shift in skin tension lines was observed. RESULTS: In older patients there was a significant shift in the skin lines with changes in positioning that was not present in the younger patients. In the older group of patients the shift in skin lines appeared to follow the direction of gravity's effect on the skin. CONCLUSION: Skin tension lines in older patients may become movable with position changes and are not static as previously stated. PMID- 8454788 TI - Human saphenous vein in vitro model for studying the action of sclerosing solutions. AB - BACKGROUND: Previous studies detailing the clinical and histologic effects of sclerosing solutions in rabbit ear and other animal vein models have provided information comparing the effects of various concentrations of hypertonic saline with and without dextrose (Sclerodex), polidocanol, scleremo (chromated glycerin), and sodium tetradecyl sulfate. OBJECTIVE: To observe short-term histologic changes of sclerosing solutions in vitro in large diameter human vein. METHODS: Human saphenous vein segments were obtained following cardiac bypass procedures. Several types of sclerosing solutions, including 23.4% hypertonic saline, 1% polidocanol, and 3% sodium tetradecyl sulfate, were allowed continuous contact with the vessel wall for 10 minutes. Test vein segments were immediately fixed and observed for histologic changes compared with normal saline controls. RESULTS: Endothelium was rapidly destroyed by all tested sclerosing solutions. Vessel wall necrosis occurred quickly with the extent determined by the sclerosing solution. Destructive potential of 3% sodium tetradecyl sulfate greatly exceeded that of 23.4% hypertonic saline or 1% polidocanol, in agreement with previous animal studies. CONCLUSION: Direct toxic effects of sclerosing agents may be compared in a constant, reproducible environment with this in vitro model. PMID- 8454789 TI - Compression stockings and non-continuous use of polyurethane foam dressings for the treatment of venous ulceration. A pilot study. AB - BACKGROUND: Venous ulceration is usually treated with Unna's boot. Recently another product, Ulcer-care, has been developed to treat these ulcers. OBJECTIVE: To evaluate the therapeutic value of Ulcer-care. METHODS: Over 24 months, 20 ambulatory patients with 30 lower extremity stasis ulcers were treated with a product consisting of: 1) a hydrophilic polyurethane sponge covered by a hydrophobic membrane changed daily or every other day; 2) an inner liner stocking that applies 10 mmHg pressure and is worn 24 hours a day; and 3) a surgical stocking with a posterior zipper that applies 30 mmHg graduated pressure and is removed at night. RESULTS: All ulcers healed after 2 to 30 weeks (mean 8.3 weeks) including 15 previously treated by Unna's boot or hydrocolloid dressings and 3 infected ulcers. CONCLUSION: The Ulcer care treatment for stasis ulcers is highly successful, easy to use, and well accepted by patients. PMID- 8454790 TI - Cool laser optics treatment of large telangiectasia of the lower extremities. AB - BACKGROUND: Lower extremity telangiectases have been traditionally treated using sclerotherapy. However, because of significant side effects from sclerotherapy, laser treatments have been investigated. Results from laser treatments have been generally unsatisfactory. OBJECTIVE: This study was based on the premise that simultaneous cooling and lasing would permit more effective treatment. METHODS: Thirty lower extremity telangiectases on 13 patients were treated by a technique of simultaneous cooling and lasing. Argon (488/514 nm) and argon dye (577 nm, 585 nm) laser light were delivered through a new cooling device to telangiectatic vessels of approximately 1-mm diameter on the thigh and leg. Pulsed and continuous beam treatments were utilized at high levels of irradiance. RESULTS: Sixty-seven percent of treated sites were improved; half of these were completely or nearly completely cleared. There were no complications. In only 2 of 30 (7%) treated sites were there persistent pigmentary changes. CONCLUSION: These results compare favorably with other methods for treatment of lower extremity telangiectases. Successful treatment of large lower extremity telangiectases by simultaneous cooling and lasing with minimal side effects suggests a reduction of thermal injury to nonvascular tissue while allowing destruction of ectatic vasculature. PMID- 8454791 TI - The frequency of skin test reactions to side-chain penicillin determinants. AB - BACKGROUND: Skin testing for immediate hypersensitivity to penicillins is usually carried out with reagents prepared from benzylpenicillin, and it is believed that side-chain-specific reactions to semisynthetic derivatives are rare. Because some experimental and clinical data suggest that antibodies can be induced to immunogenic epitopes on the side chains of penicillins, we looked for side-chain specific reactions to skin testing in patients with a history of allergy to penicillins or semisynthetic penicillins. METHODS: One hundred twelve patients with a clinical history of allergic reactions to penicillins and other semisynthetic penicillins were skin tested an average of 4.9 +/- 0.7 years after their reactions with the major and minor determinants of benzylpenicillin and minor determinant mixtures of ampicillin, amoxicillin, or cloxacillin. RESULTS: In these patients the most common clinical reactions were urticaria and angioedema (36.6%) and exanthema (48.8%). It was found that 21 cases (18.8%) still exhibited immediate hypersensitivity reactions on skin testing. But of these 21 patients, skin test reactivity was limited in 47.6% to the semisynthetic penicillin reagents derived from ampicillin, amoxicillin, or cloxacillin; that is, skin tests were negative with the benzylpenicillin derivatives. Ampicillin and amoxicillin were the semisynthetic beta-lactams causing most clinical reactions (24.1% and 33.9%, respectively), and ampicillin was the most common penicillin derivative to which skin test reactivity occurred (38.1%), other than the benzylpenicillin derivatives (52.3%). CONCLUSIONS: IgE antibodies appear therefore to discriminate between benzylpenicillin and ampicillin or other semisynthetic penicillins in a significant proportion of patients allergic to penicillin. Although it has not been proved that side-chain-specific skin reactivity implies the presence of clinically significant immediate hypersensitivity to semisynthetic penicillins, it is possible that side-chain specific reagents may be required to exclude possible immediate hypersensitivity to the penicillins in patients who reacted to these antibiotics clinically. PMID- 8454792 TI - Should we monitor peak expiratory flow rates or record symptoms with a simple diary in the management of asthma? AB - BACKGROUND: Various means of monitoring asthma severity have been proposed to reduce morbidity and mortality rates. We compared two means of assessing asthma flare-ups: monitoring peak expiratory flow rate (PEFR) and keeping a symptom diary. METHODS: This was a crossover randomized study. After a 2-week baseline period during which spirometry and PC20 methacholine were assessed, subjects were asked to record either PEFRs or to keep a symptom diary morning and evening for 6 months; a second baseline assessment separated the two periods. Subjects were asked to contact the study coordinator if the following occurred: (1) in the period of PEFR monitoring, daily fluctuations in PEFR were > 20% or the absolute value fell to < 80% of baseline or both occurred; (2) in the period of symptom diary monitoring there were nocturnal symptoms or a persistence of morning dyspnea after inhaled bronchodilator or a reduction in the duration of effect of the bronchodilator or it was impossible to go to work or school or all occurred. In that case they were asked to come to the hospital to confirm the flare-up through investigation for significant changes in FEV1 or PC20 or both. Forty subjects completed a 6-month symptom diary or PEFR recording period respectively, and 20 completed both. RESULTS: A total of 31 exacerbations were reported in 28 different subjects; three subjects had two flare-ups. Thirteen of 19 (69%) flare ups were confirmed during the symptom diary period and 9 of 12 (75%) during PEFR monitoring. Nocturnal awakenings and morning falls in PEFR > or = 20% were the most frequent occurrences. CONCLUSIONS: We conclude that a simple symptom diary may be as useful as serial PEFR monitoring in documenting asthmatic flare-ups. PMID- 8454794 TI - Development of nasal basophilic cells and nasal eosinophils from age 4 months through 4 years in children of atopic parents. AB - BACKGROUND: The importance of the inflammatory response in allergic disease has warranted investigation of two of the more integral cells in the pathogenesis of allergic rhinitis, namely, nasal basophilic cells (NBCs) and nasal eosinophils (NEs). In the present study the natural history of NBCs and NEs was studied from birth through 4 years of age in infants of atopic parents to better understand their relationship to the development of various atopic disorders. METHODS: During a prospective, randomized, controlled trial of the effect of maternal and infant food avoidance on the development of atopic disorders in 288 infants of atopic parents, NBCs and NEs were determined semiquantitatively on Wright-Geimsa stained nasal mucosal scrapings and related to each other and to various atopic parameters. RESULTS: In these infants who are at high risk NBCs developed in both those becoming atopic and those remaining nonatopic, but they occurred with increased frequency and quantity in those children in whom most allergic disorders and food or inhalant sensitization developed. NEs, rare at 4 months in all infants, increased in atopic children from 1 to 4 years, and remained infrequent and nominal in nonatopic children. Levels of NBCs and NEs (1) correlated with each other strongly, directly, and with increasing magnitude in children from ages 4 months to 4 years and (2) correlated with log serum IgE levels weakly and moderately in children from ages 2 to 4 years. Stepwise linear regression analyses revealed that allergic rhinitis accounted for most of the variance seen in the level of NBCs and NEs during early childhood, reaching 50% by age 4 years. Asthma, atopic dermatitis, food allergy, food and inhalant sensitization, serum IgE level, and IgG beta-lactoglobulin level accounted for a small proportion of the variance in NBCs and NEs from ages 4 months to 4 years. CONCLUSIONS: These findings help to elucidate the natural history of NBCs and NEs in infants at risk for atopic disorders and document the temporal association of these cells with the development of atopic disease, principally allergic rhinitis. PMID- 8454793 TI - A controlled dose-response study of immunotherapy with standardized, partially purified extract of house dust mite: clinical efficacy and side effects. AB - BACKGROUND: Seventy-four asthmatic patients allergic to house dust mite were included in a double-blind, controlled study to establish the optimal maintenance dose of a standardized extract of Dermatophagoides pteronyssinus (Der p I) during 24 months of immunotherapy (IT). METHODS: The patients were given the following maintenance doses: 19 patients 10,000 standardized quality units (SQ-U) (group 10, 0.7 microgram Der p I), 20 patients 100,000 SQ-U (group 100, 7 micrograms Der p I), 16 patients 300,000 SQ-U (group 300, 21 micrograms Der p I), and 19 control patients (group 0) had no injections. After 24 months bronchial challenge demonstrated a dose-related increased tolerance to Der p I, group 10 (p = 0.003), group 100 (p = 0.0005), group 300 (p = 0.0007), with no change in group 0 (p = 0.6). Patients given IT had a decrease in medication and peak expiratory flow score. In total, 2104 injections were given, and 3.5% were followed by a systemic reaction, defined as a fall 15% or greater in forced expiratory volume in 1 second within 30 minutes. A dose-response relation was demonstrated, with rates of systemic reactions in percent of injections; group 10, 0.56%; group 100, 3.30%; and group 300, 7.10% (p < 0.0001). No anaphylactic reactions occurred, and no late systemic reactions were observed. This study demonstrated a dose dependence of efficacy and side effects of IT in asthmatic patients. We suggest a maintenance dose of 100,000 SQ-U (7 micrograms Der p I) as an appropriate guideline for IT with house dust mite extract. PMID- 8454795 TI - Determinants of patient compliance with allergen immunotherapy. AB - BACKGROUND: Allergen immunotherapy (AIM) has been demonstrated to be safe and effective in the treatment of allergic respiratory disease. Although it requires considerable patient commitment, little attention has been paid to the factors that contribute to patient compliance. METHODS: Patients in a practice based at an urban university hospital, who discontinued AIM, were contacted to determine their reasons for stopping treatment. Results were correlated with demographic and disease data obtained from the patient charts. RESULTS: Review of practice records identified 217 patients on AIM. One hundred forty-eight had allergic rhinitis, (R), 66 had allergic rhinitis and asthma (RA), and 3 had allergic asthma without evidence of rhinitis (A). Seventy-four (50%) of the patients in the R group, 32 (48%) of the patients in the RA group, and three (100%) of those in the A group discontinued treatment. The groups differed in that 55% of the patients in the R group discontinued treatment because of inconvenience, compared with only 22% of the patients in the RA group (p < 0.01). By contrast, 25% of the patients in the RA group stopped because they thought that they were "better" with medication, compared with none of the patients in the R group (p < 0.001). All of the patients in the RA group who stopped because they were better completed at least the first four-vial treatment series. CONCLUSIONS: Inconvenience is the major contributing factor in noncompliance with AIM. Regulations designed to protect patients from adverse reactions should balance the potential risk of reactions against the benefits of treatment and the effect of more stringent guidelines on patient compliance. PMID- 8454796 TI - A double-blind, placebo controlled trial of solidified benzyl benzoate applied in dwellings of asthmatic patients sensitive to mites: clinical efficacy and effect on mite allergens. AB - BACKGROUND: The aim of this double-blind, randomized study was to investigate the effectiveness of an acaricidal cleaning product in modifying both clinical symptoms and mite allergen levels over a period of at least 1 year. METHODS: Twenty-six asthmatic patients with proven Dermatophagoides pteronyssinus (Dp) asthma were selected; three were withdrawn from the trial. The patients' homes were divided into two groups; 11 homes were treated with solidified benzyl benzoate and tenside agents (A), and 12 were treated with a placebo (P). Two applications were performed at the beginning of the trial and at least 6 months later. Patients were examined 1 month before the trial, at the beginning of the trial, and every 3 months over a period of 1 year. Indoor mite exposure was evaluated by three methods: semiquantitative guanine determinations, quantitative guanine determinations, and the measurement of Der p I + Der f 1 (antigen P, of Dp + antigen F1 of D. farinae) levels. RESULTS: The symptom scores established at the beginning of the trial and 12 months later showed a statistically significant improvement only in the A group (p < 0.01). The visual analog scale also showed a statistically significant difference both in the A (p < 0.05) and P groups (p < 0.01). No statistical differences were found between medication scores in the A or P groups. A statistically significant increase was also observed for forced expiratory volume in 1 second and maximal expiratory flow rate 25/75 in the two groups (p < 0.05 for P group; p < 0.01 for A group). The mean decreases in Der p I + Der f 1 in patient mattresses between the beginning of the trial and after 12 months were 20% for the acaricide group and 17% for the placebo group, respectively (NS). For house dust samples with origins other than the patients' mattresses we found significant decreases in Der p I+Der f 1 in the A group (p < 0.01 for carpets and p < 0.05 for upholstery elements). PMID- 8454797 TI - Hyposmia in allergic rhinitis. AB - BACKGROUND: The association between nasal allergy and loss or diminution of smell is frequently alluded to in the literature; however, neither the true prevalence of hyposmia in individuals with allergic rhinitis nor its bases have been established. METHODS: We assessed olfactory threshold for phenylethyl alcohol in 91 patients with symptoms of allergic rhinitis and 80 nonatopic control subjects. To determine the degree to which nasal congestion contributes to hyposmia in allergic rhinitis, total nasal resistance was measured in 64 of the patients and 72 of the control subjects. RESULTS: Olfactory thresholds were significantly higher in allergic patients than in control subjects (p < 0.001), with 23.1% of the patients demonstrating a clinically significant smell loss (defined as threshold at or above the 2.5th percentile of control values). Although nasal resistance was significantly higher among patients than among controls (p < 0.001), it was not related to olfactory threshold in either group. Clinical or radiographic evidence of sinusitis or nasal polyps or both in allergy patients was found to be significantly associated with hyposmia (p < 0.006). CONCLUSIONS: The observed prevalence of hyposmia among patients with allergic rhinitis suggests that this is a major etiologic factor contributing to smell disorders. Sinusitis or nasal polyps or both may underlie many cases of allergy-related hyposmia. PMID- 8454798 TI - New onset wheezing in an older male population: evidence of allergen sensitization in a longitudinal study. Results of the normative aging study. AB - BACKGROUND: Thirty-nine male subjects, with new-onset wheezing, were selected from participants in the Department of Veterans Affairs Normative Aging Study and compared with 74 age-matched controls. Wheezing was defined by responses to a standardized and regularly administered questionnaire. The subjects with wheezing had a reduced FEV1 compared with controls (p = 0.005), but most had values above 80% predicted. Current smoking was more common in subjects with wheezing (36.8% vs 8.11% in controls, p < 0.001). The mean age of both subjects and controls was 64 years. METHODS: Allergen-specific IgE antibodies were measured, starting with sera at the time of the most recent questionnaire, and on the average 3.1, 7.6, and 12.3 years before that, with use of stored serum samples. RESULTS: Total IgE did not differ significantly between the groups. IgE binding to dust mite antigen was detected in 13% to 15% of the subjects with wheezing compared with fewer than 7% of the controls over four time intervals (p = 0.014). IgE binding to cat and ragweed antigens did not differ significantly between groups. If current nonsmokers were analyzed separately, IgE binding to cat allergen was also slightly greater in subjects with wheezing compared with controls (p = 0.054). Sequential analysis of IgE antibody levels to mite antigen, over time, indicated that IgE antibody antedated the onset of wheezing. CONCLUSIONS: New-onset wheezing in an older adult male population is significantly associated with allergic sensitization to dust mite. There was a borderline association with sensitization to cat in noncurrent smokers only. This supports the hypothesis that a subgroup may have allergic triggers to their symptoms. PMID- 8454799 TI - Comparisons of specific and nonspecific bronchoprovocation in subjects with asthma, rhinitis, and healthy subjects. AB - BACKGROUND: We studied subjects with atopic asthma, atopic rhinitis, and nonatopic healthy subjects to evaluate responsiveness to bronchoprovocation with both methacholine and allergen. METHODS: Subjects with a demonstrable FEV1 PD20 to methacholine or allergen (responders) were further analyzed for putative sensitivity (PD20 FEV1) and reactivity (dose-response slopes) to determine whether any characteristics could distinguish individuals with asthma from other responders. Subjects were recruited without sex restrictions and were between the ages of 18 and 45 years old. They were nonsmokers, had no other medical problems, and were free of upper respiratory infection for at least 6 weeks before challenge. All had a history taken, physical examination, limited laboratory screening, chest radiography, pulmonary function testing, and intradermal skin testing before admission to the study. RESULTS: Although the groups were significantly different in both sensitivity and reactivity to methacholine, responses to allergen bronchoprovocation were sufficiently similar between responders with asthma and those with rhinitis to prevent separation on the basis of either sensitivity or reactivity. The fall in FEV1 at the nadir of the late response, which was greater in the asthma group, was significantly correlated with sensitivity and reactivity of the immediate response to allergen but not to methacholine. Regression analysis demonstrated a stronger association between allergen and methacholine responsiveness in subjects with rhinitis than in subjects with asthma. CONCLUSION: We concluded that (1) nonspecific bronchial hyperresponsiveness fails to explain why patients with allergic asthma have clinical asthma as a result of allergen exposure and patients with allergic rhinitis do not; (2) hyperresponsiveness to allergen does not simply reflect quantitative or qualitative airway nonspecific hyperresponsiveness; and (3) clinical asthma may involve mechanisms difficult to elucidate by laboratory bronchoprovocation techniques. PMID- 8454800 TI - Selection of representative Alternaria strain groups on the basis of morphology, enzyme profile, and allergen content. AB - In an attempt to identify representative strains, 12 strains of Alternaria alternata were contributed by four different research groups. Each was grown on two types of solid media and characterized with descriptions of pigmentation and morphology. Enzyme profiles were determined on both the cellular antigen and the culture filtrate material with use of a commercial kit. Concentrations of a previously described Alt a 1 and a 70 kd allergen, GP70, were measured by a two antibody "sandwich" ELISA. Allergenic proteins were visualized by IgE immunoblots. With use of these criteria, four separate strains were identified that might serve as representative of Alternaria for further research. PMID- 8454801 TI - Interleukin-2 and lymphocyte-induced eosinophil proliferation and survival in asthmatic patients. AB - BACKGROUND: Eosinophils are increased in the airways and blood of asthmatic patients. However, the mechanism of regulation of eosinophilia is incompletely understood. METHODS: To study the potential effect of asthmatic lymphocytes on eosinophils, lymphocytes from the blood of asthmatic patients in exacerbation, or from healthy subjects, were isolated and cultured in medium alone (LC-CM) or with interleukin-2 (IL-2-CM) (125 U/ml), and the effect of supernatant obtained from these cultures on eosinophil proliferation from progenitors and survival was studied. RESULTS: IL-2-CM from asthmatic patients significantly increased eosinophil colony formation from asthmatic blood but had no effect on colony formation from the blood of healthy subjects. IL-2-CM from asthmatic patients also significantly prolonged the survival of eosinophils. IL-2 alone and IL-2-CM from healthy subjects had no effect on eosinophil proliferation and survival. Asthmatic lymphocytes had more IL-2 receptors (CD25) than normal lymphocytes, and this difference persisted even after culture in IL-2. However, upregulation of the CD25 receptor on normal lymphocytes by incubation with concanavalin A led to the production of IL-2-CM, which did not increase eosinophil proliferation from progenitors. CONCLUSIONS: Lymphocytes from asthmatic patients but not from normal blood can significantly increase eosinophil proliferation and survival. The effects on eosinophil proliferation do not seem to be directly related to the presence of increased CD25 expression on lymphocytes. PMID- 8454802 TI - To learn the secret of success in business, listen to consumer needs. Marketing the value of dietitians' services. PMID- 8454803 TI - More thoughts on hospital malnutrition: the 'skeleton in the closet'. PMID- 8454804 TI - Partners in nutrition: RDs and the restaurant industry. PMID- 8454805 TI - Calipers vs BIA: the debate continues. PMID- 8454806 TI - New roles for RDs: diabetes case manager. PMID- 8454807 TI - Beyond nutrition screening: a systems approach to nutrition intervention. Challenges and opportunities for dietetics professionals. PMID- 8454808 TI - Trial of antihypertensive intervention and management: greater efficacy with weight reduction than with a sodium-potassium intervention. AB - The Trial of Antihypertensive Intervention and Management evaluated nine diet drug combinations in 878 mildly hypertensive, moderately obese participants using a 3 x 3 factorial design. Drugs evaluated were placebo, diuretic (chlorthalidone), and beta-blocker (atenolol); diets were usual (no intervention), weight reduction, and low sodium/high potassium (Na/K). This article reports 6-month dietary changes and the effect of dietary change on blood pressure. Six-month mean weight change was -4.7 kg in the weight reduction group, -0.3 kg in the Na/K group, and -0.5 kg in the usual-diet group. At 6 months, daily electrolyte excretion had changed in the Na/K intervention group. Daily sodium excretion decreased from 138.0 to 112.0 mmol in the Na/K group and increased from 134.1 to 138.4 mmol in the weight reduction group and from 129.1 to 137.0 mmol in the usual-diet group. Daily potassium output increased from 58.7 to 71.4 mmol in the Na/K group, from 57.0 to 60.5 mmol in the weight reduction group, and from 55.3 to 59.1 mmol in the usual diet group. Analysis of 3-day food records indicated that sodium intake decreased from 141.1 to 85.8 mmol and potassium intake increased from 76.4 to 90.5 mmol. Our results indicate that the goal for weight reduction was more easily achieved than the goal for electrolyte modification. PMID- 8454809 TI - Weight-related attitudes and behaviors of black women. AB - Weight-related attitudes and practices of women who attended health department clinics or who worked for a health and human services agency were assessed by means of an anonymous, self-administered questionnaire. Black women who were 25 to 64 years old and were not pregnant or had not given birth within the past year were included in this analysis (n = 500). The overweight women perceived themselves as being overweight. They were less likely to be satisfied with their weight and more likely to have dieted and to be currently dieting than nonoverweight women. Awareness of obesity-related health risks was high, but the perceived psychosocial consequences of being overweight were somewhat limited. Approximately 40% of moderately and severely overweight women considered their figures to be attractive or very attractive, which indicates a relatively positive body image. The overweight women were less likely to exercise, less likely to skip meals, and more likely to eat between meals than the nonoverweight women. Among the subset who had ever attempted to lose weight (n = 368), the overweight women were significantly more likely to have regained all or more of the weight lost during their most recent attempt. The findings of this exploratory survey suggest that although overweight black women are weight conscious, the absence of strong negative social pressure combined with a relatively positive body image may limit the extent to which weight loss efforts are sustained. Findings about eating and exercise patterns suggest some specific factors that may interfere with the effectiveness of weight control among black women. PMID- 8454810 TI - Perception of power among dietitians. AB - Power is a new concept in the field of nutrition that has increasing relevance for the survival of the profession in the 1990s. This study reports on dietitians' perception of power. A survey questionnaire was mailed to all members of the New Jersey State Dietetic Association (1,969 members). Usable responses were obtained from 521 dietitians (a response rate of 27%). The majority of respondents were female, married, and younger than 40 years of age; 37% were in clinical positions and 62% had completed internship and master's degree programs. Respondents rated power as very important (30%) or important (44%), and the terms accomplishments, control, intelligence, and connections were key descriptors of power. Power was felt to be acquired through knowledge, education, and position/title. The positions of department head, chief clinical dietitian, and nutrition support dietitian ranked in the middle of a power hierarchy. The top positions were chief executive officer and physician, and the bottom position was tray-line worker. Responses to "power" scenarios showed greater professional concern (60%) than personal concern (35%) over a clinical scenario (loss of control of the nutrition formulary) than a managerial scenario (threatened layoffs) (38% and 32%, respectively). Dietitians need to focus on and understand the concept and realistic use of power in the workplace. Initially, basic concepts and skills related to power must be incorporated into dietetics and continuing education using a gender-focused teaching approach. PMID- 8454811 TI - Breast-feeding reduces maternal lower-body fat. AB - The effect of breast-feeding on maternal anthropometric measures during the first 6 postpartum months was studied in 24 women. Mothers, who were seen in the hospital shortly after delivery and at monthly intervals thereafter, kept a record of their infant-feeding practices and provided three 24-hour dietary recalls per month. The women were placed in one of three groups according to their infant-feeding practices: breast-feeding exclusively, combination of breast and formula-feeding, and formula-feeding only. Changes in anthropometric variables at 6 months postpartum were similar in the three groups, but mothers who breast-fed exclusively or partially had significantly larger reductions in hip circumference measurements (3.6% and 3.1%, respectively) and were less above their prepregnancy weights at 1 month postpartum (7.8% and 8.5% above prepregnancy weight, respectively) than mothers who fed formula exclusively (0.68% reduction in hip circumference and 13.7% above prepregnancy weight). Our findings indicate that a woman's choice of infant-feeding practice influences postpartum anthropometric changes, but these effects may be temporary. PMID- 8454812 TI - Changes in resting energy expenditure and body composition in anorexia nervosa patients during refeeding. AB - Accurate prediction of the energy level necessary to promote weight restoration in patients with anorexia nervosa would be clinically useful. Resting energy expenditure (REE), respiratory quotient, and body composition were measured in 10 nonmedicated women with anorexia nervosa during a vigorous refeeding protocol. REE was measured three times per week by open-circuit indirect calorimetry after an overnight fast. Subjects ranged in age from 19 to 38 years and weighed 39.9 +/ 4.3 kg (mean +/- standard deviation) at admission. The refeeding protocol was as follows: phase 1, 1,200 kcal/day for 1 week (baseline); phase 2, an increase of 300 kcal/day for 1 week; phase 3, 3,600 kcal/day until target weight was reached; phase 4, 1,800 to 2,800 kcal/day (stabilization). REE was 30.0 +/- 6.4, 33.5 +/- 6.7, 37.3 +/- 6.6 and 34.5 +/- 4.4 kcal/kg body weight during phases 1, 2, 3, and 4, respectively. The Harris-Benedict equation overestimated phase 1 24-hour REE by a mean of 14% and underestimated REE in phases 2, 3, and 4 by a mean of 8%, 24%, and 23%, respectively. Skinfold measurements revealed percent body fat to be 12 +/- 4% at admission and 19 +/- 5% at discharge, with a mean of 48% of the weight gained during refeeding attributable to increased body fat. These findings indicate that refeeding in anorexia nervosa is associated with increased REE, which cannot be explained by increased body mass, and that caloric requirements for weight restoration in patients with anorexia nervosa are best determined by monitoring individual response. PMID- 8454813 TI - Effective provision of comprehensive nutrition case management for the elderly. AB - In response to the Nutrition Screening Initiative, we have outlined a new role for the registered dietitian (RD) in effectively providing comprehensive nutrition case management using a functional approach to nutritional status assessment of the elderly. Recommendations are provided for coordinating access to resources. We propose that through this method RDs will be seen as essential members of the health care team who will provide intervention through direct assistance with the patients. Practical steps and assessment instruments specifically designed for RDs are provided that may be incorporated into routine nutrition screening, assessment, and case management within the health care delivery practice. PMID- 8454814 TI - Obesity, weight loss, and health. AB - Obesity is a multifactorial, complicated condition or group of conditions that afflicts a growing number of people in the United States. Precise etiologies are not well understood, and both commercial and medical treatment programs are characterized by high rates of recidivism. A cultural preoccupation with slimness has created a huge industry serving millions of people who are attempting continually to reduce weight. Contradictory messages from professionals have led to confusion concerning the health implications of obesity and the potential risks of repeated dieting. This review summarizes the major areas of consensus and controversy concerning the health implications of obesity and weight loss and suggests directions for treatment that take into account the complex causes and consequences of obesity. PMID- 8454815 TI - Successful strategies for reimbursement of outpatient nutrition services. PMID- 8454816 TI - Prevalence of malnutrition in the elderly admitted to long-term-care facilities. PMID- 8454817 TI - Dietary intake of calcium, chromium, copper, iron, magnesium, manganese, and zinc: duplicate plate values corrected using derived nutrient intake. PMID- 8454818 TI - Dietary intake and growth status of young homeless children. PMID- 8454819 TI - Position of the American Dietetic Association: promotion and support of breast feeding. PMID- 8454820 TI - Insurance coverage and reimbursement--communicating in 'code'. PMID- 8454821 TI - Coding for nutrition services: challenges, opportunities, and guidelines. AB - Use of appropriate codes when billing insurance programs can be essential in obtaining reimbursement for nutrition services. The absence of codes that precisely identify the nutrition assessment and treatment functions performed by nutrition professionals on an outpatient basis is one barrier to clear and consistent processing of claims for nutrition services. Not only is there significant variation from insurer to insurer with respect to coding practices for nutrition services, but codes change over time. This article presents current codes that may be applicable to nutrition services and identifies codes designated for nutrition services by several insurers in certain areas. The article suggests the challenges and opportunities for nutrition professionals who seek to describe accurately the services they render to patients. Finally, the article discusses guidelines for professionals to consider when selecting codes to bill for nutrition services. PMID- 8454823 TI - "Legal gray areas" in low vision: the need for clarification of regulations. PMID- 8454822 TI - Nutrition care during pregnancy and lactation: new guidelines from the Institute of Medicine. PMID- 8454824 TI - Reading with low vision. AB - Most low vision patients express a desire to read standard print as easily and as quickly as possible. There are a multitude of visual factors that can interfere with reading, yet we have only an incomplete understanding of these factors. These include the relationship between acuity, magnification, and reading performance, the role of eye movements in low vision reading, and the effect of central scotomas on reading performance. We describe current research in each of these areas, and discuss their potential clinical implications. PMID- 8454825 TI - Predicting the low vision reading add. AB - Before evaluating a low vision patient with various optical aids, one should know the strength of the first lens (add) to be tried. The basic concept behind predicting this add is presented. The three most common methods of predicting the add are explained, and it is shown that all of these methods are variations of the basic concept. An analysis of the results of the three methods is given. An addendum discussing acuity notations and some common misunderstandings that occur is also included. PMID- 8454826 TI - Establishment of comprehensive low vision services in Michigan. AB - The AOA Low Vision Section presented its distinguished service award to the Michigan Commission for the Blind during the Section's 10th anniversary celebration at the 95th AOA Congress in Montreal. A progressive low vision service delivery system has evolved in Michigan over the past 22 years with optometry identified as the provider of clinical low vision care. The development of this system is described as the relationship between the Michigan Optometric Association, Michigan Commission for the Blind, and other multidisciplinary agencies is explained. Strategies for serving the visually impaired pediatric, career/vocationally aged, elderly and multiply handicapped populations in Michigan are highlighted. This historical review offers ideas for future planning as optometric low vision services are integrated into other state programs. PMID- 8454827 TI - Low vision rehabilitation of multiple sclerosis: a case report. AB - A 34-year-old white male presented with a previous diagnosis of optic atrophy secondary to multiple sclerosis, seeking low vision rehabilitation. This case report is presented to illustrate the importance of prescribing both conventional optical low vision devices, as well as computer low vision aids in order to provide comprehensive low vision rehabilitation for a young visually impaired adult. PMID- 8454828 TI - The effectivity of Fresnel prisms for visual field enhancement. AB - An objective method for placement of Fresnel prisms has been used to enhance constricted visual fields at the Eastern Blind Rehabilitation Center in West Haven, CT since 1975. To study the effectiveness of this method, 22 patients fitted with prisms since 1986 participated in a survey regarding their level of satisfaction with the prisms. Nineteen out of 22 patients continued to wear the prisms successfully, resulting in a retention rate of 86.3 percent. Of those still wearing the prisms, their reported overall satisfaction level averaged 3.63 on a scale of 1-4 (4 representing very satisfied). The reported satisfaction levels of the patients wearing the prisms were statistically analyzed with respect to pathology, months of wear, age of the patient, binocular versus monocular fitting, size of the residual field, visual acuity, the power of the prism used, and ocular rotation to enter the prism. No significant predictive value was found with any of these variables in trying to determine the level of satisfaction. However, this may be due to the small sample size. These same variables were used in comparing the patients who continued to wear the prisms with the patients who had discontinued prism use. None of these variables was found to be significant in predicting a successful outcome, possibly in part to small sample size, and the low number of unsuccessful patients. In an effort to make improvements on the existing methods being used for field enhancement, questions were asked regarding technical use of the prisms, mobility with the prisms, the spectacle carrier lens, and the maintenance of the prisms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454829 TI - A driving program for the visually impaired. AB - This driving program for the visually impaired individual was devised in 1986, as a specific adjunct to the pre-existing training program, designed for the cognitive and physically impaired patients. Two important purposes of the program are: 1) To give the low vision practitioner and staff the capability to be able to recommend a specific training program for telescopic and visually impaired drivers. 2) To try to ensure that every visually impaired telescopic driver (prescribed with a telescopic system by the low vision center) would not only meet legal visual acuity and visual field requirements for the State of Michigan, but would also improve the competency of using their telescopic system for driving. PMID- 8454830 TI - An overview of enhancement techniques for peripheral field loss. AB - Practitioners are often reluctant to deal with impaired visual function secondary to peripheral field defects. This article presents a variety of enhancement techniques that help compensate for difficulties encountered by patients with peripheral field loss. We hope the information presented will increase practitioner awareness and help in the selection of the most appropriate treatment for the particular patient. PMID- 8454831 TI - The useful field of view test: a new technique for evaluating age-related declines in visual function. AB - Many older adults eventually experience difficulty in everyday visual activities, prompting them to consult with an eye care specialist. In some cases, a thorough examination may reveal no clinical basis for these difficulties. New techniques for evaluating age-related declines in visual function have substantiated the existence of deficits in visual attention that are not adequately captured by standard clinical measures, and which are predictive of real world problems in driving and mobility. These new techniques may serve an important function in guiding the diagnosis, and treatment of those older adults experiencing functional visual problems. PMID- 8454832 TI - Changes in contact lens comfort related to the menstrual cycle and menopause. A review of articles. AB - Many women report changes in contact lens comfort during different phases of their menstrual cycle. Dryness and tearing, decreased visual acuity, swollen lids, foreign body sensations and visual coordination problems are examples of what may occur. This paper is a review of recent and older articles relating changes in contact lens comfort to modifications of the glands, conjunctiva and cornea of the eye during different phases of the menstrual cycle. Both high and low estrogen levels seem to affect the eye differently in various phases of the cycle. Some assumptions and predictions of what may happen to the eye at menopause also will be discussed. PMID- 8454833 TI - The effect of contact lens cleaners on lens parameters and surface quality of the Novalens. AB - The purpose of this study is to evaluate the effect of one abrasive cleaner, one non-abrasive cleaner and one non-abrasive alcohol-based cleaner on the lens parameter stability of the NOVALENS. Twenty-four lenses, all NOVALENS material of identical design, were cleaned 100 times each. Eight lenses were cleaned with MiraFlow (CIBA Vision), eight lenses with Optic-Free Daily Cleaner and eight lenses with the Gas Permeable Daily Cleaner (PBH). The base curve radius, center thickness and power were verified immediately before, immediately after and (per manufacturer's recommendation) 4 hours after cleaning at baseline, 25, 50, 75 and 100 cleanings. Lens toricity of approximately 0.50D was found with all three cleaners after 100 cleanings. No change in lens power or center thickness was found. It was concluded that extreme care must be taken in handling the NOVALENS due to the potential of induced warpage. PMID- 8454834 TI - Soft opaque contact lenses in binocular vision problems. AB - Soft opaque contact lenses may be useful in certain recalcitrant vision problems. When the full central area is opaque, contact lenses eliminate the visual image, provide acceptable cosmesis, and may be useful in cases of intractable diplopia as well as in the treatment of amblyopia. Artificial iris contact lenses eliminate para-axial rays in monocular diplopia, aniridia, and albinism. PMID- 8454835 TI - The effects of daily-wear contact lenses on contrast sensitivity in selected professional and collegiate female tennis players. AB - Contrast sensitivity (CS) has recently emerged as an important predictor of visual performance. Few studies, however, have been published involving CS and its role in vision for sport. The purpose of this investigation was to determine if significant differences occurred in CS between female professional and collegiate tennis players who wore daily-wear soft contact lenses (N = 10) and those players who wore no corrective lenses (N = 10) in competition as measured by the Stereo Optical Optec 2000 Vision Tester. Subjects were between the ages of 18 and 37 years. Mean ages were 21.76 (+/- 4.018) and 25.40 (+/- 5.379) years for those wearing lenses and those not, respectively. Each subject was preliminarily screened for SVA-distance, lateral/vertical phorias, stereopsis, and color perception. All subjects were within accepted limits. CS was assessed at 1.5, 3, 6, 12, and 18 cycles per degree (cpd). Each subject was assessed monocularly; eye initially assessed was determined randomly. A 2 x 2 factorial analysis of variance (alpha = .05) was used to analyze data. No significant differences were found between eyes. Significant differences were found at 3, 6, 12, and 18 cpd. It may be concluded that those female professional and collegiate tennis players wearing no corrective lenses were significantly higher in CS at intermittent and high spatial frequencies than those who wore daily-wear soft contact lenses in competition. PMID- 8454836 TI - A clinical evaluation of frequent replacement contact lenses on patients currently wearing premium reusable daily wear soft contact lenses. AB - A 3-month clinical investigation was undertaken to evaluate a population of premium reusable daily wear soft contact lens wearers when refitted with soft contact lenses worn on a daily wear schedule and replaced every 2 weeks. In addition to an initial visit, follow-up visits occurred at 2-, 4-, 8-, and 12 weeks. Areas of assessment included vision, lens fitting performance, ocular physiology, subjective comfort and handling responses and lens surface deposits and damage. Of the 51 patients recruited, 50 were successfully trial fit and enrolled. During the course of the investigation, all subjects utilized a multipurpose care regimen without the addition of an enzymatic cleaner. Upon conclusion of the investigation, 75.0 percent of the subjects chose to continue wearing the study lenses on a 2-week frequent replacement basis. PMID- 8454837 TI - EOP and Dk/L: the quest for hyper transmissibility. AB - The relationship between human equivalent oxygen percentage (human EOP) and oxygen transmissibility (Dk/L) was examined for 28 parallel- and nearly parallel surfaced contact lenses having oxygen transmissibilities ranging from 14.2 to 134.4 Dk/L units as determined with a gas-to-gas method. EOP and Dk/L were positively related such that increases in Dk/L led to progressively smaller increases in human EOP, until Dk/L asymptoted at an EOP of approximately 20 percent. Human EOPs were semi-logarithmically correlated to Dk/L in a linear fashion (R2 = 0.95), though the semi-logarithmic linear equation didn't as closely predict the expected EOP vs. Dk/L curve at its extreme ends. Classifications of oxygen transmissibility and permeability were also standardized into ranges of equivalent oxygen percentage: contact lenses of low, medium, high, super, and hyper transmissibility and materials of low, medium, high, super, and hyper permeability were defined. While most available hydrogel lenses and materials are currently limited by their water contents to the low and medium Dk/L and Dk groups, some available rigid lenses and materials have attained super-Dk/L and hyper-Dk status. They should be better able to be fitted to the individual eye and to incorporate more complicated optical corrections, having partially alleviated dependency of corneal oxygen supply on lens design. The quest for hyper-permeable materials stable in thinner designs may produce lenses of hyper transmissibility with corneal oxygen supply nearly insensitive to lens design, as variation of thickness over lens apertures will then result in alterations of corneal oxygenation (EOP) having minimal clinical significance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454838 TI - Replacement and care compliance in a planned replacement contact lens program. AB - Three-hundred and seven contact lens wearers in a planned replacement program were evaluated to determine compliance with scheduled replacement, yearly evaluation, and lens care. Patients studied were wearing soft lenses and replaced them every 6 months or less but were not using disposable lenses. Those involved were in this program for more than 24 months. The results show a 97.1 percent compliance with lens replacement and a 94.7 percent compliance with scheduled annual visits. The 32.4 percent lens care compliance rate for a single solution system was lower than expected. PMID- 8454839 TI - Comparison between "readables" aspheric spectacle lenses and conventional spherical spectacle lenses for overcorrection of presbyopic single-vision contact lens wearers. AB - Binocular spectacle overcorrection for near with "Readables" progressive-addition lenses and with lenses having spherical surfaces were compared by 36 successful presbyopic wearers of single-vision contact lenses. The two forms of near correction were each worn by these subjects for 3 weeks in a randomized cross over study and were also directly compared for 1 week in which both overcorrections were available. "Readables" spectacle correction was significantly better than the conventional overcorrection in four of the five patient response categories studied (visual comfort, close vision, intermediate vision, and function without removal) and was not significantly different in one of the five categories (ability to adapt). When asked to choose between the two near corrections, 81 percent of the subjects (29 of 36) preferred their "Readables" spectacles. It appears that "Readables" spectacle lenses offer a viable alternative to single-vision lenses when used for near correction of presbyopic patients wearing single-vision contact lenses for distance correction. PMID- 8454840 TI - Comparative efficacies of soft contact lens disinfection systems against a fungal contaminant. AB - The efficacies of five FDA-approved soft contact lens disinfecting solutions and heat disinfection were evaluated against the mold, Beauveria bassiana. Beauveria bassiana is a ubiquitous soil fungus with a demonstrated ability to grow into a soft contact lens matrix. A stock solution of the fungus was prepared and aliquots were added to each of the following disinfection solutions: ReNu Multi Purpose Disinfecting Solution, Opti-Free, AOSEPT Disinfection/Neutralization Solution, Lens Plus Oxysept 1, UltraCare, and a Softmate Thermal Disinfecting Unit. Hydrogen peroxide systems were neutralized immediately using the manufacturer's recommended method. After 1 min, 5 mins, 15 mins, 30 mins, 1 hour, 4 hours, and 8 hours; samples were removed, added to neutralizing broth, and streaked onto Sabouraud's Dextrose Agar plates. Our results showed that hydrogen peroxide and heat disinfection were much more effective against Beauveria bassiana than Opti-Free or ReNu. PMID- 8454841 TI - A longitudinal study of corneal astigmatism changes in Asian eyes. AB - This study investigated changes in corneal astigmatism with age of 494 Asian eyes in a retrospective study. The results are compared to previous studies of non Asian eyes. The current study demonstrates a greater magnitude in the rate of change of corneal astigmatism. PMID- 8454842 TI - A study of contact lens failures. AB - One hundred ninety-nine self-identified failed contact lens wearers were surveyed to determine the primary cause of their failure. Of these, 143 (72 percent) stated that comfort was the reason they had given up contact lens wear, another 39 (20 percent) failed due to inadequate visual acuity, with the remaining 17 (8 percent) failing due to convenience or economic reasons. It was determined that all were good candidates for contact lens wear; new lenses were fitted based on standard clinical findings and the patients allowed to wear the lenses for a trial period. At the end of the study period 82 percent of returning patients were successful. The author speculates that with greater care during the fitting process and a wider range of diagnostic lenses, practitioners may return the majority of contact lens dropouts to the active patient pool. PMID- 8454843 TI - Growth inhibition of a B cell clone mediated by ligation of IL-4 receptors or membrane IgM. AB - The development of B cell tolerance is believed to involve negative signaling to the B cell derived from the binding of Ag to the B cell surface Ig (sIg). B cell clones that receive negative signals via sIg may provide useful models for studying the mechanisms of negative signaling. We have recently identified a previously undescribed mouse B cell clone, CHB3, which receives growth-inhibitory signals through the binding of IL-4 to its IL-4R or through ligation of its sIgM, but not its sIgD, molecules. Data presented here demonstrate that the negative signal delivered by sIgM, but not that delivered by IL-4R, requires protein kinase C activation and elevated intracellular Ca2+, and is associated with the tyrosine phosphorylation of a number of proteins. Thus, the IL-4R signaling pathway appears to be divergent from the sIgM-mediated pathway. However, growth inhibition mediated via both sIgM and IL-4R can be partially counteracted by a signal delivered through the MHC class II molecule. PMID- 8454845 TI - IL-7 enhances the expression of IL-3 and granulocyte-macrophage-CSF mRNA in activated human T cells by post-transcriptional mechanisms. AB - The stromal derived growth factor IL-7 was studied for its ability to modulate cytokine expression in human T cells. IL-7 alone did not induce IL-3 or granulocyte-macrophage-CSF (GM-CSF) mRNA. However, IL-7 enhanced the Con A induced IL-3 and GM-CSF mRNA accumulation in a dose-dependent way. mRNA stability studies revealed that the effect of IL-7 was caused by post-transcriptional stabilization of the IL-3 and GM-CSF transcripts. Upon Con A treatment, the IL-3 and GM-CSF mRNA decayed with a t1/2 of approximately 90 and 50 min, respectively. Costimulation with Con A plus IL-7 stabilized both transcripts to t1/2 of greater than 2 h for IL-3 mRNA and 90 min for GM-CSF mRNA. Using nuclear run-on assays, we showed that the transcription rate of both genes was not affected by IL-7. Furthermore, it appeared that the effect of IL-7 was independent on protein synthesis, because cycloheximide did not abolish the promotive effect of IL-7. Finally, it was shown that in accordance with the mRNA results IL-7 enhanced the secretion of GM-CSF protein in Con A-activated T cells. After 12 h of stimulation T cells cultured in the presence of Con A secreted 575 +/- 309 pg GM-CSF/ml (x +/ SD, n = 5), which increased to 1425 +/- 758 pg/ml in the presence of Con A plus IL-7 (p < 0.01). In summary, these data demonstrate that IL-7 augments the expression and secretion of CSF in activated human T cells. PMID- 8454844 TI - Manifestation of the MHC-unrestricted killing potential of a cytotoxic T cell clone requires activation in response to MHC-restricted self-presentation of antigen. AB - 10BK.1 T clone cells of (B10 x B10.BR)F1 genotype specifically react to peptides of OVA, frequently encountered in OVA preparations, and to the synthetic peptide OVA257-264 in an H-2Kb-restricted manner; the T clone cells produce lymphokines and proliferate in the absence of added APC, suggesting self-presentation of the Ag by the T cells. In accordance with their CD8+ CD4- phenotype 10BK.1 cells exhibit cytotoxic capacity. When the target cells were pretreated with OVA257-264 only cells bearing H-2Kb molecules were lysed. However, when the relevant OVA peptide was present during the 4-h 51Cr release assay 10BK.1 cells lysed target cells expressing H-2Kb molecules as well as target cells lacking H-2Kb elements. Likewise, 10BK.1 cells pretreated with OVA257-264 for 1 h and washed extensively to remove residual Ag were able to kill syngeneic and allogeneic target cells. Killing of allogeneic targets in the presence of Ag was inhibited by antibodies directed at H-2Kb. Allogeneic target cells were not killed when 10BK.1 cells were stimulated by peptide-pulsed syngeneic cells. Triggering of the TCR/CD3 complex of 10BK.1 cells was involved during the activation phase but not during the lytic phase. IL-2 did not participate in the MHC-unrestricted killing event. To explain the observed MHC-unrestricted cytotoxicity of 10BK.1 cells, the following model is proposed. In an initial step 10BK.1 cells present the relevant OVA peptide to one another in a H-2Kb-restricted fashion. The cells are thereby triggered to mobilize the lytic machinery. In a second step sensitized 10BK.1 cells lyse allogeneic target cells. Thus, the MHC-unrestricted cytotoxicity can be dissected into an MHC-restricted phase of 10BK.1 cell activation and an MHC-unrestricted lytic phase. Cytotoxic T cells with Ag self-presentation functions may account for tissue damage during bacterial infections. PMID- 8454846 TI - Human T cell lines and clones respond to IL-9. AB - The activity of IL-9 on human T cells was investigated. Human T cell lines and clones, derived from PBMC by stimulation with PHA, IL-2, and irradiated allogeneic PBMC, were found to express a strong IL-9R message at the RNA level and to proliferate in the presence of IL-9, irrespectively of their CD4+ or CD8+ phenotype. Moreover, tumor-specific CTL clones also responded to IL-9. Contrasting with other T cell growth factors, such as IL-2, IL-4, or IL-7, IL-9 did not induce the proliferation of freshly isolated T cells. However, a significant proliferative response to IL-9 could be observed after a 10-day activation of PBMC with PHA, IL-2, and feeders. Taken together, our results indicate 1) that the activity of IL-9 on human T cells is wider than initially anticipated on the basis of the data obtained so far with murine cells; and 2) that proliferative responses to IL-9 require previous activation. PMID- 8454847 TI - Induction of functional follicular dendritic cell development in severe combined immunodeficiency mice. Influence of B and T cells. AB - Ag injected into immune mice immediately complexes with specific antibody. Immune complexes not phagocytosed by macrophages are transported by Ag transport cells to lymph node follicles for trapping by follicular dendritic cells (FDC). These FDC serve as a long term repository of unprocessed Ag that is believed to maintain both B cell memory and the secondary antibody response. Severe combined immunodeficiency mice lack functional B cells and T cells. Consequently, this mutation also appears to affect the ability to produce Ag-retaining FDC. to assess B and T cell requirements for FDC development and function, severe combined immunodeficiency mice were reconstituted with BM, or mature B and T cells. The development of a FDC reticulum, a three-dimensional network produced by the intertwining of FDC dendrites was assessed by Ag trapping on FDC using the histochemically detectable Ag horseradish peroxidase and quantitated by morphometry. The results showed that bone marrow transplants or B and T cells transferred together supply the required elements for the development of severe combined immunodeficiency FDC reticula that function in Ag trapping and the induction of the germinal center. In contrast, B cells or T cells injected separately induced a minimal development of FDC reticulum. The B and T cell requirements demonstrated here strongly indicate that B-T cell collaboration and the factors these cells produce are essential for FDC development. PMID- 8454848 TI - Cytokine production by human fetal microglia and astrocytes. Differential induction by lipopolysaccharide and IL-1 beta. AB - As part of a study on the role of cytokines in central nervous system development and dysfunction, we determined the pattern of cytokine production in highly purified cultures of microglia and astrocytes isolated from second-trimester human fetal brains. Levels of TNF-alpha, IL-1 beta, and IL-6 mRNA and protein were determined by Northern blot analysis and ELISA before and after stimulation with LPS, TNF-alpha, or IL-1 beta. In microglia, LPS induced mRNA for all three cytokines. High protein levels of IL-6 and TNF-alpha were also found in the medium, whereas IL-1 beta protein was mostly cell associated. IL-1 beta also induced message for all three cytokines, in the rank order of IL-1 beta > IL-6 > TNF-alpha. TNF-alpha induced mRNA and protein for IL-1 beta but not for TNF-alpha or IL-6. In contrast, LPS failed to stimulate either mRNA or protein expression for any of the three cytokines in astrocytes. On the other hand, IL-1 beta provided a strong stimulus for astrocytes. IL-1 beta induced mRNA and protein for both TNF-alpha and IL-6, but the kinetics of the response differed for the two cytokines. TNF-alpha mRNA and protein levels peaked early (at 4 h and 16 h, respectively) and were undetectable by 72 h, whereas IL-6 mRNA peaked later (at 16 h) and protein levels continued to accumulate in the medium through 72 h. IL-1 beta did not induce IL-1 beta mRNA or protein in astrocytes. TNF-alpha did not induce expression of any of the cytokines in astrocytes. In conclusion, our results demonstrate that cytokine production can be induced in human fetal microglia and astrocytes but that the stimuli for induction differed significantly for the two cell types. Whereas LPS was a potent stimulus for microglia, astrocytes primarily responded to IL-1 beta. The data further suggest that microglia may be key regulators of astrocyte response, working primarily through the expression of cell-associated IL-1 beta. PMID- 8454849 TI - Cross-linking of Fc gamma RIIIA on natural killer cells results in tyrosine phosphorylation of PLC-gamma 1 and PLC-gamma 2. AB - The Fc gamma RIIIA, which is composed of a transmembrane IgG-binding glycoprotein and either a disulfide-linked homodimer (zeta zeta, gamma gamma) or heterodimer (zeta gamma), mediates the antibody-dependent cellular cytotoxicity in NK cells. The role of phospholipase C (PLC) isozymes in Fc gamma RIIIA-mediated signal transduction was investigated. The NK cell line NK3.3 was found to contain PLC gamma 1 and an especially high concentration of PLC-gamma 2, but PLC-beta 1 and PLC-delta 1 were not detected. Cross-linking of Fc gamma RIIIA on NK3.3 cells induced a rapid phosphorylation of PLC-gamma 1 and PLC-gamma 2 on tyrosine residues. Pretreatment of NK3.3 cells with a tyrosine kinase inhibitor, herbimycin A, prevented the tyrosine phosphorylation of both PLC-gamma 1 and PLC gamma 2. These results indicate that activation of Fc gamma RIIIA on NK3.3 cells is coupled either directly or indirectly to a nonreceptor tyrosine kinase, which phosphorylates, and thereby activates PLC-gamma 1 and PLC-gamma 2. PMID- 8454850 TI - Mouse soluble IFN gamma receptor as IFN gamma inhibitor. Distribution, antigenicity, and activity after injection in mice. AB - With the purpose to use a soluble receptor as an IFN gamma antagonist in vivo, we assessed the immunogenicity, the half-life, the bioavailability, and the activity of the soluble receptor after injection into mice. No significant immunogenicity was detected after multiple chronic injections of mouse (Mo)IFN gamma-R or injections of MoIFN gamma-R in emulsion with CFA. Pharmacokinetic experiments using radiolabeled MoIFN gamma-R revealed that the half-life of the soluble MoIFN gamma-R is 3 h in the blood and 6 h in the lymphoid organs. When the MoIFN gamma R protein was traced by the capacity of the animal sera to displace the binding of radiolabeled MoIFN gamma-R from affinity purified rabbit anti-MoIFN gamma-R antibodies, a blood half-life of 1 h was determined. Finally, the capacity of the injected receptor to bind and neutralize the IFN gamma-mediated antiviral activity was assessed in vivo. Treatment with IFN-gamma or IFN-alpha A/D protected the mice from the lethal infection with encephalomyocarditis virus. Mice treated with MoIFN-gamma-R neutralized the protective effect of IFN-gamma. PMID- 8454851 TI - Recombinant soluble murine IL-4 receptor can inhibit or enhance IgE responses in vivo. AB - This study examines the effects of soluble IL-4R (sIL-4R) administration on IgE production in vivo by using an anti-IgD injection model. Anti-IgD-treated mice were given various doses of sIL-4R or anti-IL-4 mAb over a 3-day period and serum IgE levels were determined by ELISA on day 9. The sIL-4R inhibited IgE production by up to 85%. Anti-IL-4 mAb administration resulted in comparable levels of inhibition at considerably lower doses. The disparity in efficacy between sIL-4R and anti-IL-4 mAb was likely the result of differences in the biodistribution and in vivo half-life of the two IL-4-binding proteins. The specificity of the sIL-4R inhibitory effect was assessed by mixing sIL-4R with various concentrations of IL 4 before injection. Exogenous IL-4 partially overcame the inhibitory effect of high-dose sIL-4R or anti-IL-4 mAb. Unexpectedly, coadministration of suboptimal concentrations of anti-IL-4 mAb or sIL-4R with IL-4 resulted in superinduction of the IgE response. This stimulatory effect was dose dependent for both IL-4 and the IL-4 cognates and was not seen in the absence of exogenous IL-4 over the entire concentration range tested for either sIL-4R or anti-IL mAb. The results indicate that sIL-4R can block IgE secretion by neutralizing endogenous IL-4. Furthermore, sIL-4R can enhance, in a dose-dependent manner, the biologic effects of exogenously administered IL-4, presumably by altering the biodistribution of the cytokine. These findings suggest two alternative applications for cytokine binding proteins, i.e., 1) as antagonists of biologic activities of endogenously produced cytokines and, 2) as vehicles for cytokine delivery. PMID- 8454852 TI - Endogenous generation and presentation of the ovalbumin peptide/Kb complex to T cells. AB - Peptide fragments are displayed on the APC surface by MHC class I molecules as ligands for appropriate TCR. Sequence analysis of MHC-bound peptide mixtures has suggested that naturally processed peptides are defined by their length and by the presence of MHC allele-defined consensus motifs. To define the minimal OVA peptide presented by Kb MHC, and the requirements for generation of endogenous OVA/Kb complex, APC were transfected with OVA cDNA constructs. We show that optimal stimulation of OVA/Kb-specific B3Z T cell hybrid by Kb-APC requires the OVA257-264 peptide (SIINFEKL, SL8) whether added exogenously, or when synthesized endogenously as precursor polypeptides. Thus, all information necessary for expression of the OVA/Kb complex is contained within the Kb octapeptide motif shared by SL8. Unexpectedly, the SL8/Kb or the influenza NP/Db complexes were also generated in APC even when the peptide coding sequences were placed in incorrect translational reading frames. By contrast, identical manipulations of the translational reading frame of the lacZ reporter gene reduced protein synthesis to undetectable levels demonstrating the remarkable efficiency with which endogenous peptide/MHC are generated in and presented by APC to T cells. These characteristics of the endogenous presentation may explain how large numbers of distinct peptide/MHC complexes are displayed on the cell surface and surveyed by TCR. PMID- 8454853 TI - Influence of HLA genes on T cell receptor V segment frequencies and expression levels in peripheral blood lymphocytes. AB - The effect of the HLA complex on the TCR repertoire in human peripheral blood was assessed by using nine V beta- and V alpha-specific mAb and the quantitative polymerase chain reaction specific for 22 V beta segments. Studies in randomly selected and unrelated individuals failed to show any influence of the HLA complex on the TCR repertoire. In contrast, studies in large families with multiple siblings showed a strong influence on the TCR repertoire by the HLA complex. In pairwise comparisons, HLA-identical sibs had more similar patterns of V segment frequencies, as measured with the nine V segment-specific mAb, as well as more similar expression levels of V beta-specific RNA, as measured by quantitative polymerase chain reaction, than totally mismatched or haplo identical sibs. When the amount of V beta-specific RNA expressed in CD4+ and CD8+ T cells was compared, it was found that V beta 2, 5.1, 9, and 20 were skewed toward CD4+ T cells; on the other hand, V beta 7 and 14 showed a bias in expression for CD8+ T cells, suggesting that the former were positively selected predominantly by HLA class II gene products whereas the latter V beta segments were positively selected predominantly by HLA class I gene products. These studies unequivocally document the effects of HLA genes on TCR V segment frequencies and expression levels in peripheral blood T lymphocytes. PMID- 8454854 TI - Recombinant immunotoxins containing the VH or VL domain of monoclonal antibody B3 fused to Pseudomonas exotoxin. AB - We prepared recombinant immunotoxins in Escherichia coli in which the VH or VL domains of mAb B3 were fused to a truncated form of Pseudomonas exotoxin (PE) (PE38KDEL). mAb B3 binds to a carbohydrate Ag found on the surfaces of many types of cancers and only a few normal tissues. PE38KDEL is a 38-kDa form of PE (66 kDa) that is missing the cell-binding domain of PE and has the carboxyl end changed from REDLK to KDEL. We show that immunotoxins in which the H chain or the L chain V region is fused to PE38KDEL bind to and kill carcinoma cells containing the B3 Ag. B3 Ag-negative cells were not affected. The cytotoxicity of these molecules is between 20- and 100-fold less than B3(Fv)-immunotoxins, containing both the H and L chain V regions. The VL-containing toxin was more active than the VH-containing toxin, indicating that the L chain of mAb B3 probably contributes more to Ag-binding than the H chain. Refolding experiments show that B3(VL)-PE38KDEL aggregates less than the VH-derivative or than a single chain immunotoxin B3(Fv)-PE38KDEL, which contains both domains in a single chain form. Furthermore, in addition to monomers, active homodimers of B3(VH)- and B3(VL) PE38KDEL were obtained from renaturation experiments. The VL-toxin dimers, which might have their binding regions arranged in a manner similar to Bence Jones proteins (L chain homodimers), were found to have almost the same cytotoxicity as the monomers, whereas the VH-toxin dimers had decreased cytotoxic activity. PMID- 8454855 TI - VH gene expression and regulation in the mutant Alicia rabbit. Rescue of VHa2 allotype expression. AB - Rabbits of the Alicia strain, derived from rabbits expressing the VHa2 allotype, have a mutation in the H chain locus that has a cis effect upon the expression of VHa2 and VHa- genes. A small deletion at the most J-proximal (3') end of the VH locus leads to low expression of all the genes on the entire chromosome in heterozygous ali mutants and altered relative expression of VH genes in homozygotes. To study VH gene expression and regulation, we used the polymerase chain reaction to amplify the VH genes expressed in spleens of young and adult wild-type and mutant Alicia rabbits. The cDNA from reverse transcription of splenic mRNA was amplified and polymerase chain reaction libraries were constructed and screened with oligonucleotides from framework regions 1 and 3, as well as JH. Thirty-three VH-positive clones were sequenced and analyzed. We found that in mutant Alicia rabbits, products of the first functional VH gene (VH4a2), (or VH4a2-like genes) were expressed in 2- to 8-wk-olds. Expression of both the VHx and VHy types of VHa- genes was also elevated but the relative proportions of VHx and VHy, especially VHx, decreased whereas the relative levels of expression of VH4a2 or VH4a2-like genes increased with age. Our results suggest that the appearance of sequences resembling that of the VH1a2, which is deleted in the mutant ali rabbits, could be caused by alterations of the sequences of the rearranged VH4a2 genes by gene conversions and/or rearrangement of upstream VH1a2 like genes later in development. PMID- 8454856 TI - Promoter of the human NF-kappa B p50/p105 gene. Regulation by NF-kappa B subunits and by c-REL. AB - NF-kappa B is a transcription factor involved in the regulation of numerous genes encoding proteins involved in immune function, in inflammation or in cellular growth control. NF-kappa B is typically characterized as a heterodimer of a 50 kDa subunit (p50) and a 65-kDa (p65) subunit. Interestingly, the p50 subunit is derived by processing of a 105-kDa precursor. Induction of NF-kappa B DNA-binding activity involves both the release of cytoplasmically stored factor from its inhibitor known as I kappa B and the induction of NF-kappa B gene expression. We report here the cloning and functional analysis of the promoter of the p50/p105 NF-kappa B gene. Our data suggest the existence of multiple transcription initiation sites for this gene in the B cell line Raji, Jurkat T cells, and HeLa cells. The promoter is constitutively active in these cells and is inducible by phorbol ester and mitogen stimulation of Jurkat T cells. Expression of I kappa B inhibits this inducible activation of the p50/p105 promoter. Furthermore, we have shown that co-transfection of a p50/p105 promoter-reporter plasmid with expression vectors encoding the p50 or p65 subunits of NF-kappa B or c-Rel results in stimulation of gene expression. Supportive of the transfection data, we have identified a DNA-binding site for NF-kappa B in the promoter of the p50/p105 gene that is responsive only to a combination of p50 and p65. The data demonstrate that the p50/p105 NF-kappa B gene is regulated by members of the NF kappa B/Rel family and likely by other important transcription factors. PMID- 8454857 TI - Transcriptional control of MHC class I and beta 2-microglobulin genes in vivo. AB - The expression of class I and beta 2-microglobulin (beta 2-m) genes, which encode the H and L chains of the H-2 histocompatibility Ag, respectively, is complex both in the adult mouse and during development. Although they are ubiquitously expressed in the adult, the mRNA levels of these genes are variable from one organ to another, being high in liver, lung, and lymphoid organs and low in brain and testis. During development, both class I and beta 2-m mRNA are poorly expressed. To determine the molecular mechanism, either transcriptional or post transcriptional, controlling class I and beta 2-m mRNA levels, we have compared their transcriptional activities by performing run-on experiments with nuclei extracted from several embryonic and adult organs. We show that most of the differences observed in H-2 and beta 2-m mRNA steady state levels are the reflection of their different transcriptional activities. These results demonstrate that MHC class I and beta 2-m gene expression in adult organs, as well as during development, is mainly controlled at the transcriptional level. PMID- 8454858 TI - The gamma subunit of the B cell antigen-receptor complex is a C-terminally truncated product of the B29 gene. AB - The predominant Ag-receptor complex of B cells consists of mIgM or mIgD noncovalently associated with glycosylated heterodimers of Ig-alpha and Ig-beta or Ig-alpha and Ig-gamma. Upon B cell stimulation the associated proteins are phosphorylated, giving rise to pp32/33 (alpha), pp37 (beta), and pp34 (previously designated gamma). Ig-alpha and Ig-beta contain extended cytoplasmic structure (61 and 48 amino acids, respectively) and associate with cytoplasmic effectors indicating that they are directly involved in signal transduction. Here we report analysis of the structural relationship of mIgM- and mIgD-associated Ig-beta and Ig-gamma chains from mice. N-terminal sequence, immunoblotting, and physicochemical analyses show that both Ig-beta and Ig-gamma are products of the B cell-specific B29 gene and demonstrate that the 37-kDa Ig-beta protein is the full length predicted product of the B29 gene. The Ig-associated protein that migrates in the 34-kDa range is actually two distinct species. The minor species is a phosphorylatable and underglycosylated form of full length Ig-beta, and the major species is a C-terminally truncated form of B29, which we now designate Ig gamma. This conclusion is based on the observations that Ig-gamma is composed of a core protein which is 3 to 4 kDa smaller than deglycosylated Ig-beta, it is not phosphorylated, unlike Ig-beta, and it does not react with an antiserum raised against a peptide of the seven C-terminal amino acids of B29. Based on these findings we estimate that Ig-gamma is truncated by about 30 to 36 amino acid residues and hypothesize that the most 3' B29 exon, which encodes the 32 C terminal residues, may not be expressed in Ig-gamma. All of the documented B29 products are found in association with both mIgM and mIgD. Interestingly, Ig gamma is found in intermediate and low density splenic B cells, but is not detectable in resting B cells. This raises the possibility that it may confer some distinct signaling function on the Ag receptors of these cells. PMID- 8454859 TI - Sequence analysis and antigenic cross-reactivity of a venom allergen, antigen 5, from hornets, wasps, and yellow jackets. AB - Ag 5 is a major allergen of vespid venom. The complete amino acid sequences of Ag 5 from two species each of hornets (Dolichovespula arenaria and maculata), wasps (Polistes annularis and exclamans), and yellow jackets (Vespula maculifrons and vulgaris) have been determined by amino acid sequencing and/or cDNA cloning. The sequence data reveal several conserved and variable regions for vespid Ag 5. The conserved regions show greater sequence similarity than do the less conserved regions to a family of proteins from human, mouse, and rat testis and to a class of pathogenesis-related proteins from tobacco and tomato leaves. Tests in the murine system for both T and B cell responses demonstrate a high degree of cross reactivity of hornet Ag 5 with wasp or yellow jacket Ag 5 and a low degree of cross-reactivity of yellow jacket Ag 5 with wasp Ag 5. This pattern of cross reactivity is in the same order as their sequence similarity. PMID- 8454860 TI - Evolution of the MHC: isolation of class II beta-chain cDNA clones from the amphibian Xenopus laevis. AB - The amphibian Xenopus laevis is the most primitive vertebrate in which the MHC has been identified both at the biochemical and functional levels. In the present study, cDNA clones for MHC class II beta-chain genes of X. laevis were isolated using the polymerase chain reaction. In partially inbred animals with the MHC f haplotype, two distinct cDNA clones assumed to encode isotypes were identified. The deduced MHC class II beta-chains of X. laevis had structures fundamentally similar to those of their mammalian counterparts. The overall amino acid sequence identity between X. laevis and representative mammalian MHC class II beta-chains was approximately 41 to 50%. Sequence comparison of cDNA clones isolated from outbred subjects and the partially inbred frog with the MHC f haplotype showed that nucleotide substitutions are located primarily in the beta 1 domain and that non-synonymous substitutions occur more frequently than synonymous substitutions in the putative Ag-binding sites. This result indicates that, as in mammalian MHC genes, the MHC class II beta-chain genes of X. laevis are under positive Darwinian selection. Despite the fact that X. laevis is a tetraploid species, its MHC, as defined by serology, immunochemistry, and MLR, is diploidized. Family studies showed that all MHC class II beta-chain genes detectable in the genome of X. laevis segregate with serologically defined MHC haplotypes, suggesting that the second, inactivated set of MHC class II beta-chain genes was either deleted or that their sequences diverged too far to be detected by DNA hybridization. Furthermore, a nearly constant number of MHC class II beta-chain genes was detectable in most, if not all, Xenopus species with various degrees of ploidy. Thus, various polyploid species of Xenopus appear to have used a similar strategy to diploidize their MHC genes. PMID- 8454861 TI - Chromosomal organization of the human VH4 gene family. Location of individual gene segments. AB - To investigate the organization and evolution of VH gene segments, we characterized the elements belonging to the VH4 gene family from the germline of a single subject. One hundred sixty VH4-carrying lambda-phage clones were isolated from a genomic library. A combination of hybridization and sequence analysis yielded 13 distinct VH4 clones. Six of these elements had one or more nucleotide substitutions that distinguished them from previously identified VH4 genes, whereas seven elements were identical to previously described VH4 genes. In four of the six new sequences, nucleotide substitutions resulted in amino acid replacements. One pseudogene was identified. On the basis of sequence-specific hybridization using oligonucleotide probes corresponding to these sequences, each of the elements could be assigned to a specific band in a BglII digest. Since the VH4-carrying BglII bands have been mapped in genomic DNA, it was also possible to assign chromosomal locations to the specific VH4 elements. The results indicate that the majority of VH4 elements are located in a region of approximately 500 kb, extending from approximately 500 to 1000 kb 5' of the JH locus. The distribution of shared structural motifs among the VH4 elements indicates that the VH4 gene family has evolved through repeated duplication and gene conversion events. PMID- 8454862 TI - TNF-alpha response of human monocyte-derived macrophages to Mycobacterium avium, serovar 4, is of brief duration and protein kinase C dependent. AB - Human monocyte-derived macrophages (M phi) from the majority of normal donors respond to inoculation with Mycobacterium avium, serotype 4, (MAI) by elaboration of the inflammatory monokines TNF-alpha, IL-1 beta, and IL-6, which are of central importance for the protection against bacterial and parasitic infections. Peak TNF-alpha mRNA levels were of brief duration, being maximal at 1.5 h, and were only slightly higher than background levels at 4 h. Increases of IL-1 beta and IL-6 mRNA levels, on the other hand, persisted for 48 to 72 h. In contrast to LPS, MAI induced the production of only small amounts of TNF-alpha protein in the first 12 h and of large amounts of IL-1 beta and IL-6 protein between 3 and 72 h. MAI-induced TNF-alpha transcripts, in contrast to LPS induced TNF-alpha transcripts, were highly unstable. Their accumulation was blocked and their t 1/2 significantly decreased by the protein kinase C inhibitor staurosporine. In contrast, LPS-induced increases of TNF-alpha mRNA levels and MAI-induced increases of IL-1 beta and IL-6 mRNA levels were PKC independent. The cAMP- and cGMP-dependent protein kinase inhibitors, KT5720 and KT5823, respectively, and the tyrosine kinase inhibitors herbimycin and erbstatin had no effect on the MAI dependent mRNA accumulation of TNF-alpha, IL-1 beta, and IL-6. W7, a calmodulin dependent protein kinase inhibitor, was inhibitory in all cases. Thus, MAI induced TNF-alpha mRNA accumulation is of short duration and PKC dependent. MAI induced TNF-alpha protein production is low, possibly resulting in a mitigated antimicrobial effect. PMID- 8454863 TI - Characterization of T helper cell responses to the trypanosome variant surface glycoprotein. AB - T cell responses to the variant surface glycoprotein (VSG) previously have not been detected in animals infected with the African trypanosomes despite the fact that such animals make strong T-dependent B cell responses to VSG molecules displayed by the parasites. In the present study, we have examined B 10.BR mice for VSG-specific Th cell responses at different times after infection with Trypanosoma brucei rhodesiense clone LouTat 1. T cell populations derived from different tissues were tested for their ability to proliferate and secrete cytokines when stimulated with purified LouTat 1 VSG. Furthermore, VSG-specific T cell lines and clones were derived from immunized mice and examined for their phenotypic and functional profiles in comparison with T cell responses of infected mice. The results of this study show that VSG-specific T cells were not consistently detected in the peripheral lymphoid tissues such as spleen or lymph nodes of infected animals. In contrast, VSG Ag-specific T cells were detectable principally in the peritoneal T cell populations of infected mice. Peritoneal T cells did not proliferate in response to VSG, yet produced substantial cytokine responses when stimulated; the cytokines produced were IFN-gamma and IL-2, without detectable IL-4. The cellular phenotype of VSG-responsive T cells was that of classical Th cells in that all cells were CD4-positive and expressed the CD3 alpha/beta TCR membrane complex. Thus, the VSG appears to preferentially stimulate a Th1 cell subset response during infection. Intrinsic molecular characteristics of the VSG molecule did not induce mice to make this response, however, since VSG-specific T cell lines derived from VSG-immunized mice displayed cytokine profiles characteristic of both Th1 and Th2 cells. Isolation of Th1 clones from selected lines demonstrated that these cells displayed the same membrane-phenotypic characteristics and cytokine profiles as the T cells from infected mice. Furthermore, all Th clones were VSG type-specific, APC dependent, and I-Ak-restricted in their responses. In summary, these experiments provide the first direct evidence for VSG-specific responses at the T cell level. T cell responses to the VSG molecule during infection appear to be anatomically compartmentalized and exhibit evidence of clonal maturation (cytokine production) but not clonal expansion (proliferation) after antigenic stimulation. The cellular phenotype and cytokine profiles predict that infection predisposes the animals to mount Th1 cell subset responses to VSG. The results of this study, including the T clones generated, provide an experimental basis for examining the regulation of VSG-specific immune responses during infection. PMID- 8454864 TI - Macrophage phagocytosis of virulent but not attenuated strains of Mycobacterium tuberculosis is mediated by mannose receptors in addition to complement receptors. AB - We have examined macrophage receptors that mediate phagocytosis of virulent strains (Erdman and H37Rv) and an attenuated strain (H37Ra) of the intracellular pathogen, Mycobacterium tuberculosis. Adherence of the three strains to monocyte derived macrophages (MDM) is markedly enhanced (>threefold) in the presence of low levels of fresh serum and requires heat-labile serum components because heat inactivation of serum reduces adherence by 65 +/- 5 to 71 +/- 2%. In the presence and absence of serum, adherence of the three strains to MDM is comparable. By electron microscopy, all bacteria are ingested and reside in phagosomes. C receptors (CR) play an important role in adherence of the three strains to MDM in the presence and absence of serum. mAb against CR1, CR3, and CR4 inhibit adherence of Erdman M. tuberculosis in fresh serum by 75 +/- 3% and inhibit the low level of adherence of Erdman (71 +/- 13%), H37Rv (72 +/- 1%), and H37Ra (64 +/- 14%) M. tuberculosis in the absence of serum. Mannose receptors (MR) play an important role in mediating macrophage adherence of the virulent strains but not the attenuated strain of M. tuberculosis. Preincubation of MDM with soluble mannan or mannose-BSA consistently and significantly inhibits adherence of Erdman and H37Rv (up to 60 +/- 7%) but not H37Ra (0 +/- 1 to 5 +/- 5% enhancement of adherence) in the absence of serum. Down-modulation of macrophage MR on mannan substrates inhibits adherence of Erdman (52 +/- 8%) and H37Rv (55 +/- 6%) but not H37Ra (2 +/- 2% enhancement of adherence). Preincubation of MDM with soluble N acetylglucosamine-BSA also significantly inhibits adherence of the virulent strains (42 +/- 3%). Preincubation of MDM with glucose-BSA minimally inhibits adherence of the three strains (2 +/- 4 to 12 +/- 5%). Anti-MR antibody inhibits adherence of Erdman (57 +/- 2%) and H37Rv (44 +/- 4%) but not H37Ra (4 +/- 5% enhancement of adherence). Inhibition of adherence of zymosan was comparable with that seen with virulent strains of M. tuberculosis in these studies. Down modulation of macrophage MR also inhibits adherence of Erdman (48 +/- 9%) and H37Rv (20 +/- 2%) in the presence of serum. Simultaneous blockade of MR and CR does not further inhibit adherence of the virulent M. tuberculosis strains over that seen with blocking CR alone.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8454865 TI - Characterization of a recombinant T cell and B cell reactive polypeptide of Onchocerca volvulus. AB - To identify potentially protective Ag of the filarial nematode Onchocerca volvulus on the molecular level we screened a cDNA library of O. volvulus with a human serum raised against radiation-attenuated infective larvae of O. volvulus. A cDNA clone of 218 bp (OvL3-1) was selected for further studies. It was expressed in Escherichia coli and affinity purified recombinant polypeptide was tested for its ability to stimulate in vitro PBMC from African onchocerciasis patients and PBMC from chimpanzees experimentally infected with O. volvulus. An enhanced cell proliferation by PBMC was observed in many patients after stimulation with the recombinant OvL3-1 polypeptide. In addition, some patients' PBMC responded to OvL3-1 stimulation with enhanced IL-2 production. Infected chimpanzees also showed an increase in T cell proliferation. Onchocerciasis patients had variable levels of specific antibodies directed to the recombinant polypeptide when sera were tested by ELISA. A mAb directed against the recombinant protein located the native target Ag in the muscles of the adult worm. The molecular mass of native OvL3-1 was found to be 50 kDa on immunoblots. Polymerase chain reaction analysis of RNA from different life stages of the parasite showed that OvL3-1 is transcribed in all parasite stages within the mammalian host. A homologous gene is also present in other filarial parasites. The protein corresponding to OvL3-1, therefore, represents an immunogen present during the whole life-span of the parasite, and because of its B and T cell stimulatory properties, it may be a candidate for a protective Ag in human filariasis. PMID- 8454866 TI - Colonial morphotype as a determinant of cytokine expression by human monocytes infected with Mycobacterium avium. AB - Mycobacterium avium is an intracellular pathogen that causes disseminated infection in patients with AIDS. Colonial morphotype (smooth-transparent (SmT) vs smooth-domed (SmD)) is a key determinant of virulence in mice and the capacity for replication in human monocytes. Some cytokines (IL-1 and IL-6) promote, whereas others (IFN-gamma and TNF) inhibit intracellular M. avium growth. The specific factors that determine virulence of M. avium, however, are not clear. In this study, we examined cytokine expression by human monocytes stimulated with isogeneic cloned isolates of M. avium. Monocytes were prepared from healthy donors and cultured with or without isogeneic M. avium for up to 7 days. Cytokine levels (IL-1, IL-6, and TNF-alpha) in monocyte supernatants and cell lysates were measured by immunoassay using an ELISA. The expression of cytokine mRNA by monocytes infected with M. avium also was determined by extracting total RNA and subjecting it to Northern blot analysis. Optimal cytokine release occurred at 24 h. SmD induced higher levels of the following cytokines in supernatants than SmT: IL-1 alpha (140 +/- 32 (mean +/- SE) vs 47 +/- 16 pg/ml, p < 0.02), IL-1 beta (4.0 +/- 0.9 vs 1.7 +/- 0.5 ng/ml, p < 0.01), and TNF-alpha (2725 +/- 546 vs 1464 +/- 409 pg/ml, p < 0.01). IL-6 production was comparable for both strains. SmD and SmT isolates induced comparable levels of steady state mRNA for IL-1 beta, TNF, and IL-6. Pulse-chase analysis indicated that differences in cytokine expression between SmT and SmD occurred in monocyte lysates at the earliest time point (immediately after pulse-labeling). The dissociation of the expression of specific mRNA from production of IL-1 and TNF suggests that translational capacity for the expression of certain cytokines was reduced by the more virulent SmT. Differential induction of cytokine may be a factor in the pathogenicity of M. avium strains isolated from patients with AIDS. PMID- 8454867 TI - Exogenous nitric oxide (NO) generation or IL-1 beta-induced intracellular NO production stimulates inhibitory auto-ADP-ribosylation of glyceraldehyde-3 phosphate dehydrogenase in RINm5F cells. AB - Nitric oxide (NO) stimulates the auto-ADP-ribosylation of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) which results in the inhibition of enzyme activity. In the present work we show that addition of exogenous NO or IL-1 beta-induced intracellular NO generation cause GAPDH ADP-ribosylation and inhibition of enzyme activity. Incubation of RINm5F cells with sodium nitroprusside (SNP) for 18 h caused a time- and dose-dependent inhibition of GAPDH activity. Half-maximal inhibition of GAPDH activity was observed with 80 microM of the NO donor, with maximal inhibition after roughly 6 h of incubation. In parallel, SNP induced endogenous ADP-ribosylation of GAPDH measured by a decreased incorporation of [32P]ADP-ribose from [32P]NAD+ in the cytosol of the SNP-treated cells. Stimulation of endogenous NO production by inducing the NO synthase by exposure to the cytokine IL-1 beta results in decreased GAPDH activity. IL-1 beta (10(-9) M) inhibited GAPDH activity about 55%, compared with control values. Production of nitrite and inhibition of GAPDH was reversed by the NO synthase inhibitor NG-monomethyl-L-arginine, indicating that endogenous generated NO was the effective molecule. Again, GAPDH inhibition was associated with NO-stimulated endogenous ADP-ribosylation of the enzyme. Western blot analysis of GAPDH excluded degradation of GAPDH by NO. NO-stimulated auto-ADP ribosylation resulted in inhibition of the glycolytic enzyme GAPDH and may be relevant as a cytotoxic effect of NO. In concert with its inhibitory actions on iron-sulfur enzymes like aconitase and electron transport proteins of the respiratory chain NO may mediate autocytotoxic effect in beta-cells. PMID- 8454868 TI - Identification of a chemotactic domain of the pro-inflammatory S100 protein CP 10. AB - We previously reported the purification and partial amino acid sequence of a novel murine cytokine designated CP-10, which has chemotactic activity for murine polymorphonuclear cells (PMN) and macrophages. The complete cDNA encoding an 88 amino acid polypeptide has been isolated and the sequence is presented here. Transient transfection of CP-10 cDNA into CV-1 cells confirmed the chemotactic activity of rCP-10 for murine PMN. CP-10 has sequence homology with members of the S100 family of Ca(2+)-binding proteins with pronounced amino acid sequence similarities within the putative N- and C-terminal Ca(2+)-binding sites, but differences within their connecting hinge and C-terminal regions. We have confirmed the hypothesis of Kligman and Hilt that functional specificity of individual members of the S100 protein family may reside in the hinge region. A synthetic peptide corresponding to the hinge region of CP-10 (CP-10(42-55) was compared with native CP-10 in chemotaxis and skin test assays. Native CP-10 had potent activity for phagocytic cells, but not lymphocytes, in vitro (optimal activity, 10(-11) to 10(-13) M) and elicited a sustained recruitment of neutrophils and mononuclear cells over 24 h in vivo. The hinge-region peptide had strong chemotactic activity for murine phagocytic cells (optimal activity, 10( 10) - 10(-11) M) but elicited only a transient infiltration of neutrophils over 4 to 8 h after intradermal injection. Results indicate that although the hinge region contributes significantly to the functional specificity of the S100 protein CP-10, sustained cellular recruitment typical of a delayed type hypersensitivity response is apparently dependent on the structural integrity of the protein. PMID- 8454869 TI - The serine protease cofactor factor V is synthesized by lymphocytes. AB - Ag-specific cellular immune responses result in CD4+ T cell activation, which can induce the expression of tissue factor in cells of monocyte/macrophage lineage. This results in initiation of the coagulation protease cascade, with ultimate generation of thrombin. The latter is a potent and pleiotropic mediator of cellular responses and deposition of fibrin. To explore the requirements for extravascular cellular mediation of immune effector pathways, we have searched for a cellular source of the cofactor factor Va. Factor V mRNA was identified in human lymphoid cells by using reverse transcription followed by the polymerase chain reaction (RT-PCR). We confirmed our reverse transcription-polymerase chain reaction results by an independent cloning of factor V cDNA from a T cell cDNA library. The sequence of the factor V cDNA was virtually identical to hepatic factor V mRNA sequence. A limited span of mRNA, encoding part of the connecting region of the factor V protein, was found to contain nucleotide polymorphisms based on six nucleotide substitutions. Northern blot analysis confirmed the presence of a approximately 7-kb factor V mRNA in the Hut-78* human T lymphoma cell line and, at five- to eightfold less abundance, in unstimulated lymphocytes and long term allogeneic stimulated T cells. Immunocytology with factor V mAb identified factor V intracellularly in freshly isolated T lymphocytes but not on the surface of cells. These data provide evidence for factor V transcription and biosynthesis by human lymphocytes. They provide an additional perspective on how lymphocytes may contribute to inflammatory effector functions of cellular immune responses in extravascular sites through provision of cofactors necessary for the coagulation serine protease cascade. PMID- 8454870 TI - Differential regulation of formation of multinucleated giant cells from concanavalin A-stimulated human blood monocytes by IFN-gamma and IL-4. AB - We found that in vitro multinucleated giant cells (MGC) could be produced by incubation of highly purified human blood monocytes with Con A alone, and the effect of Con A was dose- and time-dependent. Any of the cytokines considered as macrophage-activating factor, such as IFN-gamma, IL-2, IL-4, GM-CSF, or TNF alpha, did not induce MGC by itself. When added to monocyte cultures, however, IFN-gamma enhanced Con A-induced MGC formation in a dose-dependent manner. In contrast, IL-4 suppressed this response in a dose- and time-dependent manner. IL 4 antagonized the enhancing effect of IFN-gamma on Con A-induced MGC formation. This ability to suppress the formation of MGC was completely abrogated after treatment with anti-IL-4 antibody. In addition, the involvement of monokines (IL 1 alpha, IL-1 beta, IL-6, and TNF-alpha) in Con A-induced monocyte fusion was investigated by adding various antimonokine polyclonal antibodies in cultures. Normal rabbit IgG, anti-IL-1 alpha rabbit antibody, and anti-IL-1 beta rabbit antibody had no effect on Con A-induced MGC formation. However, anti-TNF-alpha rabbit antibody had suppressed the monocyte fusion induced by Con A in a dose dependent manner, and a high dose of anti-IL-6 rabbit antibody had a partially suppressive effect. Anti-TNF-alpha mAb also had an inhibitory effect on monocyte fusion. Furthermore, the enhancing effect of IFN-gamma on this response was entirely abrogated by anti-TNF-alpha rabbit antibody. There was a highly significant positive correlation between the fusion rates of monocytes and the levels of TNF-alpha produced by monocytes (r = 0.68, p < 0.0005). Our results indicate that T cell-derived lymphokines, such as IFN-gamma and IL-4, have mutually antagonistic effects on Con A-induced human MGC formations in vitro, in which the expression of TNF-alpha in human monocytes plays a key role in the fusion process of monocytes. PMID- 8454871 TI - Human recombinant macrophage inflammatory protein-1 alpha and -beta and monocyte chemotactic and activating factor utilize common and unique receptors on human monocytes. AB - The human macrophage inflammatory proteins-1 alpha and -beta (MIP-1 alpha and beta), which are also known as LD78 and ACT2, respectively, are distinct but highly related members of the chemoattractant cytokine (chemokine) family. rMIP-1 alpha and -beta labeled with 125I specifically bind to human peripheral blood monocytes, the monocytic cell line THP-1, peripheral blood T cells, and the YT cell line. Steady state binding experiments revealed approximately 3000 high affinity binding sites/cell for MIP-1 alpha on human monocytes and on THP-1 cells, with Kd values of 383 pM and 450 pM, respectively. Human MIP-1 alpha and beta had nearly identical affinities for the binding sites and each competed equally well for binding. Human monocyte chemotactic and activating factor (MCAF), a member of the same chemokine family, consistently displaced about 25% of human MIP-1 alpha and -beta binding on monocytes but not on YT cells, which did not bind MCAF. On the other hand, human rMIP-1 alpha and -beta partially inhibited binding of radiolabeled MCAF to monocytes. Both MIP-1 alpha and -beta were chemotactic for human monocytes. Preincubation of monocytes with human rMIP 1 alpha or -beta markedly reduced cell migration towards the other cytokine, whereas preincubation with human rMCAF only partially desensitized the monocyte chemotaxis response to human rMIP-1 alpha or -beta. These data suggest the existence of three subtypes of receptors, i.e., one unique receptor shared by MIP 1 alpha and -beta, a second unique receptor for MCAF, and a third species that recognizes both MCAF and MIP-1 peptides. PMID- 8454872 TI - Identification of potent mixed leukocyte reaction-stimulatory cells in human bone marrow. Putative differentiation stage of human blood dendritic cells. AB - Dendritic cells (DC) have been isolated from blood, lymphoid tissue, and other tissues, as potential members of a hemopoietic lineage of specialist APC for naive T lymphocyte activation. To define human bone marrow (BM) DC we have attempted to identify allostimulatory cells with DC-like characteristics among human BM mononuclear cells (BMMC) by FACS cell sorting and immunophenotyping, monitoring the APC function of different cell lineages in the human primary MLR. We show that fresh human BM stimulates allogeneic T lymphocytes with an activity equal to or greater than that of peripheral blood. As with DC from other tissue sources, the most potent stimulatory activity was found in the low density BMMC, and these cells, like peripheral blood, stimulated a maximal allogeneic MLR response at days 5 to 6. FACS purification of the allostimulatory population in fresh human BMMC was undertaken by using a wide range of mAb directed against lineage-associated molecules of mature and immature lymphoid, erythroid, and myeloid cells. The most potent constitutive BMMC stimulatory activity was located in the CD3-, CD11b-, CD14-, CD15-, CD16-, CD19-, CD57-, and glycophorin A- population. A mixture of antibodies to these Ag was used to isolate a "mix negative" BMMC population, which contained the most highly potent MLR-stimulatory cells. Further cytologic and immunophenotypic analysis of this population revealed an enriched population of HLA-DP+, HLA-DQ+, HLA-DR+, and CD45+ cells, with morphologic similarities to the human tonsil and blood DC. These cells were CD4- and CD1a- and were weakly CD33+ (but CD15-), suggesting a possible early myeloid origin distinct from both the committed granulocytic and monocytic lineages. In addition, they lacked both CD10 and CD20, making a lymphoid origin unlikely. Further identification of these putative DC precursors will allow analysis of the early phases of DC hemopoiesis, whereas the characterization of the MLR-stimulatory cells in human BM will be of major importance in the understanding of BM transplant failure and graft-vs-host disease. PMID- 8454873 TI - Antitumor activity of the single-chain immunotoxin BR96 sFv-PE40 against established breast and lung tumor xenografts. AB - We have constructed a single-chain immunotoxin consisting of the variable H and L chains of the carcinoma-reactive mAb BR96, fused to the binding defective protein toxin, PE40. This molecule, BR96 sFv-PE40, has been shown to be extremely cytotoxic toward a variety of BR96 Ag-expressing tumor cell lines. When administered i.v. into athymic mice carrying L2987 tumor xenografts, BR96 sFv PE40 was cleared rapidly from the blood with a half-life of approximately 30 min. This is in comparison to a chemical conjugate, chiBR96-LysPE40, that remained in the blood for almost 2 h. In addition, the smaller single-chain immunotoxin (67 kDa) penetrates the tumor faster than the larger chemical conjugate (190 kDa). Using a variety of administration schedules and doses, we treated established human tumor xenografts in athymic mice with both the single-chain immunotoxin BR96 sFv-PE40 and the chemical conjugate chiBR96-LysPE40. In both L2987 lung carcinoma and MCF-7 breast carcinoma models, we found that BR96 sFv-PE40 completely regressed the tumor xenografts. With an administration schedule of q4dx5, the tumors were totally regressed and did not reappear. The chiBR96 LysPE40 conjugate produced partial tumor regressions, although at near maximum tolerated dose. These results show that the single-chain immunotoxin, BR96 sFv PE40, is a potent antitumor agent. PMID- 8454874 TI - Circulating HIV-specific CD8+ cytotoxic T cells express CD38 and HLA-DR antigens. AB - CD38, a molecule with multilineage distribution but unknown function, and the MHC class II molecule HLA-DR (DR) have markedly elevated levels of expression on CD8+ cells of HIV-infected people. This study investigated the expression of CD38 and DR Ag on circulating HIV-specific CD8+ CTL in HIV-seropositive subjects. Purified CD8+ lymphocytes from 22 participants in the University of California at Los Angeles Multicenter AIDS Cohort Study were screened for CTL activity against autologous EBV-immortalized lymphoblast targets infected with vaccinia vectors that carried HIVIIIB gag, pol, and env genes. Sixty-seven percent (14 of 21), 64% (14 of 22), and 9% (2 of 22), respectively, of the subjects had HIV-specific CD8+ CTL activity against gag, pol, and env proteins. CD8+ cells from 11 of the subjects who had high CTL activity were then FACS-separated using three-color immunofluorescence sorting. Circulating DR-CD38- CD8+ cells had little activity. Highly purified DR+CD38+ CD8+ cells had higher HIV-specific CTL activity than other CD8+ cells. DR+CD38- or DR-CD38+ CD8+ cells also mediated significant activity, but only about half as much on a per cell basis as DR+CD38+ CD8+ cells. This is the first report that the CD38 molecule is expressed in vivo on Ag specific CD8+ CTL, and confirms previous reports that DR is expressed on these cells. Both asymptomatic HIV-seropositive subjects (144 +/- 132/mm3) and AIDS patients (253 +/- 178/mm3) had markedly elevated levels of DR+CD38+ CD8+ cells compared with the levels in HIV-seronegative controls (7 +/- 3/mm3). However, the level of anti-HIV CTL activity was not correlated with the level of DR+CD38+ CD8+ cells, indicating that enumeration of this lymphocyte population by flow cytometry most likely will not be a useful surrogate for measuring functional CTL activity. Low levels of HIV-specific CTL activity, especially against gag, were correlated with lower CD4+ cells numbers, suggesting that the loss of CD8+ T cell cytotoxic activity against HIV that has been reported to occur with advancing HIV disease progression may reflect in part the extent of CD4+ cell immunodeficiency in HIV-infected subjects. PMID- 8454875 TI - Monoclonal antibody to rubella virus capsid protein recognizes a beta-cell antigen. AB - The high frequency of insulin-dependent diabetes (IDDM) in children with congenital rubella suggests that the infectious agent may trigger the autoimmune process. To explore the immunologic relationship between rubella virus and IDDM, we examined a panel of mAb that recognizes rubella virus capsid and envelope glycoproteins for reactivity with islet cell Ag. One mAb, C9, which recognizes a defined domain within the capsid protein of rubella virus, was found to react with extracts from a rat beta-cell tumor and normal rat and human islets. Using one and two dimensional immunoblot analysis of rat beta-cell tumor extracts, the C9-like epitope was found to reside on a 52 kDa protein that is also the target of autoantibodies from human IDDM and nonobese diabetic mice. To confirm this cross-reactivity, antibodies in diabetic sera were absorbed to the recombinant rubella virus capsid protein, eluted, and then shown to react with the 52 kDa insulinoma protein. These data show that an immunogenic epitope on the rubella virus capsid protein is mimicked by a similar structure on a beta-cell protein. These findings suggest that rubella virus has the potential to sensitize susceptible individuals for an autoimmune response to beta-cell Ag and identify one mechanism that may contribute to beta destruction in IDDM. PMID- 8454876 TI - The anti-idiotypic response by cynomolgus monkeys to humanized anti-Tac is primarily directed to complementarity-determining regions H1, H2, and L3. AB - The anti-ld response developed by cynomolgus monkeys to the humanized anti-Tac antibody was analyzed by using 12 humanized anti-Tac variants differing in V region structure. The majority of the monkey response was directed against idiotopes composed wholly or in part of complementarity-determining regions H1, H2, and L3. There was no detectable response directed solely to five single complementarity-determining regions examined or solely to the modified human V region framework. PMID- 8454877 TI - Characterization of the mouse autoantigen La (SS-B). Identification of conserved RNA-binding motifs, a putative ATP binding site and reactivity of recombinant protein with poly(U) and human autoantibodies. AB - To facilitate the study of autoimmunity to the nuclear Ag La (SS-B) we have isolated and characterized cDNA encoding the mouse La (SS-B) protein. Mouse La (SS-B) protein has 76.7% identity to both human and bovine La (SS-B) proteins and the previously recognized RNP-binding motifs were noted to be highly conserved across the three species. Examination of the primary sequence of human and bovine La (SS-B) newly identifies the site of a potential ATP-binding motif G/AXXXXGK which is preserved in mouse La (SS-B) despite a unique 16 amino acid insertion present in this region of the mouse protein. Analysis of mouse genomic DNA suggests a single gene encodes mouse La (SS-B) and no restriction fragment polymorphisms were identified in the three mouse strains investigated. Two alternate 5' untranslated regions were identified in mouse La (SS-B) cDNA and La (SS-B) mRNA was identified in a wide range of murine tissues consistent with its ubiquitous expression. Recombinant mouse La (SS-B) protein purified from Escherichia coli was shown to bind to poly(U) agarose and to react with sera containing anti-La (SS-B) antibodies obtained from patients with Sjogren's syndrome. The ability to produce recombinant mouse La (SS-B) should provide a valuable reagent for the study of the cellular autoimmune response as well as immunologic tolerance to La (SS-B) Ag in mice. PMID- 8454878 TI - Immunization with recombinant BCG-SIV elicits SIV-specific cytotoxic T lymphocytes in rhesus monkeys. AB - Because the transmission of HIV is likely to occur through cell-associated virus, an effective HIV vaccine should be capable of eliciting HIV-specific CTL. We have employed the simian immunodeficiency virus (SIV)/rhesus monkey model to explore the use of the attenuated tuberculosis bacillus, Calmette Guerin bacillus (BCG), as a vaccine vehicle to elicit AIDS virus-specific CTL. BCG was engineered to express SIVmac gag under the control of hsp70 regulatory sequences. Immunization with this rBCG-SIVmac gag elicited MHC class I-restricted, CD8+ SIVmac gag specific CTL in rhesus monkeys. In fact, SIVmac gag-specific CTL could be cloned readily from peripheral blood lymphocytes of these immunized monkeys. These findings provide further evidence for the power of BCG as a vaccine vector and its continued exploration as a vehicle for eliciting HIV-specific immunity. PMID- 8454879 TI - Tres difficile. PMID- 8454880 TI - Orthostatic hypotension in HIV infection in Africa. PMID- 8454881 TI - The use of antiprotozoan and anthelmintic drugs during pregnancy and contraindications. PMID- 8454882 TI - Effect of nomadic shepherds and their sheep on the incidence of cryptosporidiosis in an adjacent town. PMID- 8454883 TI - Helicobacter pylori and gastric carcinoma. PMID- 8454884 TI - Screening of patients with diarrhoea in the U.K. for cyanobacteria-like bodies. PMID- 8454885 TI - Haemolytic anaemia in Campylobacter enteritis. PMID- 8454886 TI - HIV testing among injecting drug users in Glasgow. AB - The use of saliva rather than blood for epidemiological studies of HIV prevalence, especially among injecting drug users, has several practical advantages. In a cross-sectional, behavioural and prevalence study among drug users in Glasgow during 1990, salivary samples were therefore obtained by the use of salivettes. Such samples were requested for anonymous anti-HIV testing from 498 persons in locations varying from residential rehabilitation centres to the open streets. Of this number, 35 refused to give a sample, resulting in a compliance rate of 93%. Of the 463 salivettes received by the laboratory, eight were found to be dry. Of the remaining 455 specimens, eight were found to be positive for HIV-1 antibody by means of an IgG antibody capture ELISA, so giving a prevalence rate of 1.8%. The results of testing saliva and blood spot samples collected at the same time on filter paper from 98 persons for HIV-1 antibody were 100% concordant. The study confirms the experience of others that specimens of saliva are easy to collect under variable conditions by non-medical staff and demonstrates that the salivette can provide an HIV antibody test result the same as that obtained from a blood spot. The prevalence of HIV antibody determined in this study is similar to that of other studies taking place in the city during the same period of time. PMID- 8454887 TI - Tuberculosis and AIDS: is the white plague up and coming? AB - We have studied the effect of the HIV epidemic on the incidence of tuberculosis in an inner city area of London which has a high incidence of acquired immunodeficiency syndrome (AIDS). During the period 1985-1991, there was a steady increase in the number of new AIDS cases, whilst the numbers of notifications and laboratory isolates of Mycobacterium tuberculosis remained largely unchanged. Before 1990 there were few cases of tuberculosis in HIV-infected individuals but in the past 2 years there has been a marked increase. In 44% of patients, the site of infection was pulmonary, in 39% extrapulmonary and in 17% pulmonary and extrapulmonary. There were no previous manifestations of immunodeficiency in 58% of patients. This is the first study to show an association between tuberculosis and HIV in the U.K. and supports the suggestion that there is an increased incidence of tuberculosis in patients with HIV infection who are not intravenous drug users. PMID- 8454888 TI - Acute and long-term efficacy of antituberculous treatment in HIV-seropositive patients with tuberculosis: a study of 36 cases. AB - Thirty-six consecutively observed HIV-seropositive patients with tuberculosis, including 31 patients with AIDS, who received antituberculous treatment, were followed up to evaluate its efficacy. Treatment with standard antituberculous regimens was intended except when an individual's condition required a modified therapeutic approach. Therapeutic failure occurred in five patients (14%) while on treatment, one also had a post-treatment relapse. Treatment failure was associated with drug resistance and non-compliance in three patients and in another two, both of whom died early in the course of their disease, with HIV related conditions other than tuberculosis. The median relapse-free post treatment follow-up time in 24 patients in whom treatment did not fail was 13 months (range 4-67). Standard antituberculous treatment is highly effective in the immediate and long-term treatment of HIV-related tuberculosis provided that drug susceptibility and treatment compliance are confirmed. PMID- 8454889 TI - Gastro-intestinal involvement in Mycobacterium avium-intracellulare infection of patients with HIV. AB - In a study of 866 faecal specimens from 437 persons, Mycobacterium avium intracellulare (MAI) was isolated from 14.8% patients with AIDS and 1.3% patients with symptomatic HIV infection but not from any HIV seronegative or asymptomatic HIV seropositive persons. These data support the hypothesis that the gastro intestinal tract is the portal of entry for MAI and confirm that MAI infection is a manifestation of late-stage HIV disease. Positive faecal cultures correlated well with disseminated disease. The use of faecal cultures for early diagnosis is therefore recommended. PMID- 8454890 TI - A parasitologically proven case of Toxoplasma pneumonia in an immunocompetent pregnant woman. AB - We report a case of primary pulmonary toxoplasmosis in an immunocompetent pregnant woman. Seroconversion did not occur until 2 weeks after detection of the parasite in bronchoalveolar lavage fluid. It is suggested that toxoplasma infection should be considered in any atypical pneumonia in which the X-ray shows diffuse pulmonary infiltrates. PMID- 8454891 TI - Disseminated Mycobacterium flavescens in a probable case of chronic granulomatous disease. AB - We report the case of a diabetic Chinese male with no previous history of recurrent infections. His course was at first notable for relapsing Salmonella blockley infections, following which he developed repeated soft-tissue infections and Cryptococcus neoformans pneumonia. He was diagnosed as having chronic granulomatous disease and was treated with gamma interferon. During the latter stages of his illness he developed Mycobacterium flavescens infection in soft tissues, joints, bones and lung. This is the first report of disseminated M. flavescens infection. PMID- 8454892 TI - Aseptic arthritis associated with herpes zoster. AB - Arthritis associated with herpes zoster is rarely reported. We describe the clinical features of an immunocompromised 54-year-old woman who developed sterile arthritis of a knee in association with acute ipsilateral zoster of the L1/L2 dermatomes. PMID- 8454893 TI - Successful treatment of Candida albicans osteomyelitis with fluconazole. AB - The case of a 63-year-old man who developed Candida albicans osteomyelitis is reported. Because of renal impairment, fluconazole was chosen as treatment rather than amphotericin B. The patient made a full recovery. This is the first report of the successful use of fluconazole in the treatment of candidal osteomyelitis. PMID- 8454894 TI - Oral acyclovir to prevent dissemination of varicella in immunocompromised children. AB - Twenty-five immunocompromised children with varicella were treated with oral acyclovir 800 mg, five times daily for 7 days. Two patients were transferred from the oral to the intravenous route: one had signs of varicella pneumonitis on routine X-ray, the other had continuing new lesion formation on day 4 of oral treatment. The disease healed in all patients, with no other evidence of dissemination. In an historical placebo treated group, 12 of 25 patients were transferred to intravenous acyclovir. The reduction to two of 25 is statistically significant (P < 0.01). The mean peak plasma acyclovir concentration in these patients was 6.56 mumol/l. Mild, self-limiting diarrhoea in nine patients was the only adverse event considered to be related to acyclovir. It is concluded that immunocompromised children with varicella can be treated safely and effectively with oral acyclovir. All patients should be observed closely by a physician. PMID- 8454895 TI - Acute myeloid leukaemia presenting with acute Branhamella catarrhalis epiglottitis. AB - Acute supraglottic laryngitis and epiglottitis is increasingly recognised in adults. We present a case in which the condition was the presenting feature of acute myeloid leukaemia and in which Branhamella catarrhalis was the causative organism. PMID- 8454896 TI - Helicobacter (Campylobacter) fennelliae-like organisms as an important but occult cause of bacteraemia in a patient with AIDS. AB - We describe the isolation and identification of a Helicobacter (Campylobacter) like organism obtained from the blood of a 32-year-old homosexual man with a 10 months' history of AIDS and progressive mucocutaneous Kaposi sarcoma. Fever and bacteremia persisted despite sequential administration of ciprofloxacin and trimethoprim-sulfamethoxazole, antibiotics reported to be active against this organism in vitro. Facultative organisms like Campylobacter fennelliae and Campylobacter cinaedi which are difficult to isolate by standard techniques may be important but unrecognized causes of febrile illness in patients with human immunodeficiency virus infection. Laboratories should consider use of acridine orange staining and more extensive subculture protocols for blood cultures with progressive growth indices which appear negative by conventional staining and subculture technique. PMID- 8454897 TI - Inhibition of neutrophil adherence to antibody by dapsone: a possible therapeutic mechanism of dapsone in the treatment of IgA dermatoses. AB - Dapsone is frequently effective in cutaneous diseases characterized by antibody deposition and accumulation of neutrophils. We hypothesized that this mechanism of action of dapsone may involve the inhibition of neutrophil adherence to antibody. The neutrophil adherence assay, which measures the binding of neutrophils to basement membrane zone-bound antibody on skin sections, was used to evaluate the effect of dapsone on neutrophil adherence to immunoglobulin A and immunoglobulin G. We evaluated the effect of dapsone on adherence of normal neutrophils to immunoglobulin A and immunoglobulin G from sera of linear immunoglobulin A bullous dermatosis and bullous pemphigoid patients, respectively. Linear immunoglobulin A bullous dermatosis or bullous pemphigoid antibody were bound to the basement membrane zone of normal skin sections as a substrate for the neutrophil adherence assay. Dapsone was added directly to the neutrophils or to the antibody source in concentrations of 0-50 micrograms/ml (pharmacologic range). Addition of dapsone to neutrophils produced an incremental inhibition of neutrophil adherence up to 75% at 50 micrograms/ml. Dapsone produced similar inhibition when added directly to the antibody itself, despite washing prior to usage in the neutrophil-adherence assay. Control specimens including irrelevant fractions of patient sera failed to demonstrate binding. Serum from a patient on dapsone therapy also showed inhibition of neutrophil adherence compared to the same patient on no therapy. We conclude that dapsone inhibits the adherence of neutrophils to basement membrane zone antibody in a dose-dependent manner. This may be related to an effect directly on antibody. This inhibition may contribute to the clinical efficacy of dapsone in antibody mediated diseases. PMID- 8454898 TI - Pigmentation and inhibition of wound contraction by cultured skin substitutes with adult melanocytes after transplantation to athymic mice. AB - Wound closure with cultured skin substitutes results in epithelium that is consistently hypopigmented. Hypothetically, addition of human melanocytes to cultured skin grafts may result in normal pigmentation of healed skin. Skin substitutes were composed of human epidermal keratinocytes and melanocytes, dermal fibroblasts, and collagen-glycosaminoglycan substrates, and were incubated for 12 d in media for keratinocyte growth (KG, n = 4), for keratinocyte differentiation containing four fatty acids and vitamin E with basic fibroblast growth factor (KDF, n = 6) or epidermal growth factor (KDE, n = 6), or for melanocyte growth (MG, n = 6) with phorbol ester and 5% fetal bovine serum. Skin substitutes were grafted orthotopically to full-thickness skin wounds (2 x 2 cm) on athymic mice, and scored for percent original wound size (+/- SEM), visible pigmentation (number pigmented/n), and positive staining for human leukocyte antigens (HLA)-ABC after 6 weeks on the mice. The data show that cultured skin grafts containing human melanocytes that are incubated in KDE or MG media have statistically significant reduction in wound contraction, 1:1 correlation of expression of pigment and HLA-ABC, and increased frequency of pigmentation after healing compared to incubation in KG or KDF media. Transmission electron microscopy confirmed the presence of melanocytes, melanosomes, and pigment transfer to keratinocytes in pigmented skin. These results suggest that survival and differentiated function of cultured epithelium can support melanization of skin, and that skin analogues exposed to phorbol ester in vitro can support skin pigmentation after wound healing. PMID- 8454899 TI - Structural variations in anchoring fibrils in dystrophic epidermolysis bullosa: correlation with type VII collagen expression. AB - Dystrophic epidermolysis bullosa is characterized by various abnormalities of anchoring fibrils, which are mainly composed of type VII collagen, at the dermal epidermal junction. To define these changes more clearly, we examined skin samples from 22 patients with different forms of dystrophic epidermolysis bullosa by pre-embedding immunoelectron microscopy using an antibody (LH 7:2) that binds to the NC-1 globular domain of type VII collagen, followed by 1 nm colloidal gold labeled secondary antibodies and subsequent silver enhancement. In dominant dystrophic epidermolysis bullosa cases, there was only a slight but variable reduction in the immunolabeling density on anchoring fibrils and on the lamina densa, in parts similar to normal human skin. In localized recessive dystrophic epidermolysis bullosa skin, some fibrillar structures just below the lamina densa (and particularly subjacent to hemidesmosomes) had specific antibody labeling despite their lack of resemblance to definitive anchoring fibrils. Immunolabeling with LH 7:2 was also seen within basal keratinocyte endoplasmic reticulum and cytoplasmic vesicles in some dystrophic epidermolysis bullosa patients, usually with milder phenotypic features. Even in the most severe cases of generalized recessive dystrophic epidermolysis bullosa, occasional immunolabeling was found within the lamina densa and on scanty thin filamentous structures at sub-lamina densa sites usually occupied by anchoring fibrils. This study suggests that dystrophic epidermolysis bullosa patients express some type VII collagen NC-1 domain epitopes that may be variably reduced at the dermal-epidermal junction or retained within basal keratinocytes. The clinical heterogeneity in dystrophic epidermolysis bullosa is mirrored by a range of immunoelectron microscopy findings, indicating variability in completeness of anchoring fibril formation and a possible spectrum of underlying type VII collagen structural protein abnormalities. PMID- 8454900 TI - Desmocollins I and II are recognized by certain sera from patients with various types of pemphigus, particularly Brazilian pemphigus foliaceus. AB - Recently, it has been shown that desmoglein, pemphigus foliaceus target antigen, and a 130-kD pemphigus vulgaris antigen belong to the cadherin family of cell adhesion molecules. We tried to determine whether desmocollins I/II, other cadherin-like transmembranous glycoproteins present in desmosomes, are also recognized by pemphigus autoantibodies of the IgG class. We examined 16 pemphigus vulgaris sera, 15 pemphigus foliaceus sera, 15 Brazilian pemphigus foliaceus sera, five bullous pemphigoid sera, and 65 normal sera. Four (25%) pemphigus vulgaris sera, one (7%) pemphigus foliaceus serum, eight (53%) Brazilian pemphigus foliaceus sera, and three (5%) normal sera reacted with desmocollins I/II on immunoblots of bovine desmosome preparation. The affinity-purified desmocollins I/II pemphigus autoantibodies were shown to bind the epidermal cell surface by indirect immunofluorescence. Immunoblot analysis revealed one pemphigus vulgaris serum, one Brazilian pemphigus foliaceus serum, and one normal serum recognizing a recombinant protein produced by a desmocollin cDNA clone. Moreover, immunoblot analysis of reactivity of a Brazilian pemphigus foliaceus serum with recombinant proteins produced by deletion mutants of the desmocollin cDNA clone showed that the extracellular portion of desmocollin is immunogenic in this pemphigus patient. We conclude that desmocollins I/II are recognized by certain sera from patients with various types of pemphigus, particularly Brazilian pemphigus foliaceus. However, the significance of this reactivity remains to be defined. PMID- 8454901 TI - Immunohistochemical localization of SKALP/elafin in psoriatic epidermis. AB - Recently we have reported the purification and biochemical characterization of a new, inducible elastase inhibitor [skin-derived antileukoproteinase (SKALP)], which could be extracted in high amounts from psoriatic skin but not from normal human skin. Here we demonstrate the immunohistochemical localization of SKALP in psoriatic epidermis. SKALP was found exclusively in the upper layers of the suprabasal compartment and stratum corneum of lesional psoriatic epidermis. Basal keratinocytes were always negative. No immunoreactive SKALP was found in normal epidermis and non-lesional psoriatic epidermis, in accordance with findings in functional assays. Western blots of skin extracts from psoriatic and normal skin confirmed the immunohistochemical findings and revealed two major bands with apparent molecular weights of 10.5 and 11.5 kDa. We would hypothesize that SKALP could act as a modulator of epidermal inflammation by interfering with polymorphonuclear leukocyte trafficking, and that it could protect structural proteins against elastase-mediated damage. PMID- 8454902 TI - Purification and immunohistochemical localization of aspartic proteinases in rat epidermis. AB - Investigation of skin cathepsin E (EC 3.4.23.-) has been totally ignored compared to skin cathepsin D (ED 3.4.23.5). In this study both cathepsins E and D were simultaneously purified to homogeneity up to 370 and 640 times, respectively, from 2-day-old rat epidermis. The total aspartic proteinase activity of rat epidermis detected after Q-Sepharose column chromatography was attributed to 27% cathepsin E, 63% cathepsin D, and 10% other enzymes. The purified enzymes showed that cathepsin E (90 kDa) is a dimer of 45 kDa subunits whereas cathepsin D is a monomer of 42 kDa. Other biochemical properties of epidermal cathepsins E and D were similar to those reported from other tissue sources. Immunologically cathepsins E and D were distinct from each other and localization of the two enzymes differed in both rat and human skin by immunohistochemistry. Cathepsin E was distributed diffusely in the cytoplasm of almost all epidermal cells, though its concentration increased above suprabasal cells, whereas cathepsin D appeared in particulate form only in cells of the granular layer. The findings indicate that two aspartic proteinases that have similar enzymatic properties exist in the epidermis. They are, however, differentially distributed in the organ, presumably for different functions during the process of keratinization. PMID- 8454903 TI - Rate of stratum corneum formation in the perinatal rat. AB - During late gestation, the fetal rat exhibits marked hyperplasia of the interfollicular epidermis and accelerated cornification in preparation for birth. In this study, we utilized simple morphometric techniques to provide quantitative estimates of the rate of stratum corneum (SC) formation during the perinatal period. Cryostat sections of dorsal epidermis from rat pups between -48 and +72 h of age were expanded under alkaline conditions and the number of corneocyte interfaces counted from photomicrographs. This method yielded the following regression lines: prenatal, y = 0.19x + 13.07, r = 0.93; postnatal, y = 0.13x + 13.00, r = 0.93, where y = number of SC layers and x = age in hours. Lack of desquamation was assured by the postnatal persistence of the granular periderm. Adhesive stripping of the epidermis followed by phase-contrast microscopy revealed intact monolayer sheets of SC. Quantitation using a computerized image analysis system gave an average corneocyte surface area in the newborn rat of 1908 +/- 36 mu 2 (mean +/- SEM). Treatment of neonatal rats with epidermal growth factor (500 ng/g BW) increased the number of SC layers over the first 24 h of life (p < 0.05) and resulted in marked hyperkeratosis by one week of age. These results allow the following conclusions: 1) in the prenatal rat, SC forms at a rate of one layer every 5 h; 2) postnatally, SC formation slows to one layer every 8 h; 3) to support normal corneum synthesis at birth, dorsal keratinocytes must enter transition at a rate of approximately 3 cells/second/cm2 of body surface; and 4) treatment with exogenous EGF augments the rate of terminal differentiation of perinatal rat epidermis. PMID- 8454904 TI - Ontogeny of water sorption-desorption in the perinatal rat. AB - In mammals, birth marks a transition to a cold and gaseous environment that requires rapid physiologic adaptations limiting heat and water loss. In this study, the perinatal Sprague-Dawley rat was utilized as a model to study the behavior of water binding to the external body surface following birth. Water sorption and desorption were quantified by measurement of skin surface capacitance following water loading using a dry ring electrode system. The results indicate that the external body surface of the newborn rat is highly hydrophobic. This hydrophobicity is manifested by the rapid desorption of water (amniotic fluid) following birth as well as marked limitation of water sorption after birth. Post-natally, this hydrophobic effect is gradually lost over the first 3 d of life. Somatic growth retardation results in retention of this surface property, whereas extraction of the skin surface with acetone abolishes it. Morphologic and functional (water binding) studies performed after stripping the stratum corneum with acrylic adhesive strongly suggest a physiologic role for the periderm in determining this postnatal hydrophobic effect. These data are interpreted as evidence for a novel thermoregulatory mechanism in the rat during adaptation to post-natal life. PMID- 8454905 TI - Presence of anti-La(SS-B) is associated with binding to the 13-kD carboxyl terminus of 60-kD Ro(SS-A) in systemic lupus erythematosus. AB - In systemic lupus erythematosus (SLE) clinical manifestations, autoantibody production, and immunogenetics are inter-related. The ability to study parts of the autoimmune response may allow a more detailed understanding of these relationships. We undertook this study to determine whether the fine specificity of the autoimmune response to 60-kD Ro(SS-A) was related to the presence of other autoantibodies. We screened 74 patients with SLE for antibodies to the carboxyl 13-kD terminal of 60-kD Ro(SS-A) (13 kD). Twenty-five sera had such antibodies. This reactivity was distinguished by the presence of not only anti-Ro(SS-A) but also other antibodies. All nine sera with Ro(SS-A) and La(SS-B) Ouchterlony immunodiffusion precipitins bound 13-kD (p = 0.01), whereas 10 of 11 sera with both anti-Ro(SS-A) and anti-La(SS-B) as determined by immunosorbent assay bound 13-kD (p = 0.002). Inhibition studies demonstrated that antibodies binding the 13 kD fragment bound the 60-kD Ro(SS-A) protein but did not bind the La(SS-B) protein. Thus, anti-La(SS-B) was found in those sera that bound epitopes within the 13-kD carboxyl terminal of 60-kD Ro(SS-A). These data suggest a structural basis by which anti-Ro(SS-A) and anti-La(SS-B) are coupled in SLE. PMID- 8454906 TI - Tissue-related and species-specific differences in the 2-5A oligomer size requirement for activation of 2-5A-dependent RNase. AB - 2',5'-Oligoadenylate (2-5A)-dependent RNase (L or F) is the final enzyme in the 2 5A pathway and a key component in the molecular mechanism of interferon (IFN) action. Here we demonstrate differences in the 2-5A oligomer size requirement between rabbit 2-5A-dependent RNase from reticulocytes and from cultured kidney cells. The rabbit reticulocyte enzyme was activated by tetramer 2-5A, whereas the ribonuclease from rabbit kidney cells required only trimer 2-5A. Interestingly, in contrast to the 2-5A-dependent RNase from rabbit reticulocytes, that from murine reticulocytes could be activated by trimer 2-5A. Partial proteolysis of affinity-labeled, 80-kD 2-5A-dependent RNase from rabbit reticulocytes and rabbit kidney cells resulted in the same pattern of labeled peptides. However, the affinity labeling reaction with a 32P-labeled 2-5A analog did produce some different labeled polypeptides in rabbit kidney cell extract and rabbit reticulocyte lysate. These results could indicate specialized functions for the 2 5A system in different organ systems. PMID- 8454907 TI - Isoforms p69 and p100 of 2',5'-oligoadenylate synthetase induced differentially by interferons in vivo and in vitro. AB - Four isoforms of 2',5'-oligoadenylate (2-5A) synthetase have been identified (40, 44, 69, and 100 kD). The 40- and 44-kD enzymes are encoded by the same gene, probably different from the genes encoding the larger isoforms. In this study, induction of the 100- and 69-KD (p100, p69) isoforms in different individuals and in different cell types was investigated after treatment with recombinant human interferons (IFN): IFN-alpha 2, IFN-beta ser, or IFN-gamma. The p69 and p100 isoforms were quantitated in cell extracts on Western blots using specific polyclonal antibodies, or their activity was measured after purification of cell extracts on immunoaffinity columns. The p69 and p100 isoforms were differentially induced in Daudi, fibroblast, and colon adenocarcinoma cells treated with IFNs. Considerable individual variations in both basal and induced levels of p69 and p100 were observed in peripheral blood mononuclear cells from normal donors cultured with IFNs in vitro, and from cancer patients treated with IFN-alpha 2 or with IFN-beta ser. These results demonstrate that the p69 and p100 isoforms are present in vivo in peripheral blood mononuclear cells and their level is increased following IFN administration. Furthermore, both the in vivo and in vitro observations indicate that the expression of these enzymes is specific to each cell type and varies among individuals. PMID- 8454908 TI - Role of serotonin in the regulation of interferon-gamma production by human natural killer cells. AB - Monocytes, recovered directly from peripheral blood by counter-current centrifugal elutriation (CCE), were shown to provide two regulatory signals for induction of interferon-gamma (IFN-gamma) in natural killer (NK) cells in response to interleukin-2 (IL-2): an upregulating signal and an inhibitory signal. The inhibitory signal was time-dependent, irreversible, and operating on a pretranslational level, as indicated by the inability of enriched NK cells to accumulate IFN-gamma mRNA in the presence of elutriated monocytes. Monocyte induced inhibition of IFN-gamma production was abrogated by the biogenic amine serotonin, acting via the 5-hydroxytryptamine, or serotonin (5-HT1A), subset of serotonin receptors (5-HTR). Thereby, serotonin effectively promoted IFN-gamma production in the presence of monocytes. We conclude that serotonergic 5-HT1A receptors transduce signals that are required for NK cells to produce IFN-gamma in response to IL-2. PMID- 8454909 TI - Immunochemotherapy of visceral leishmaniasis: a pilot trial of sequential treatment with recombinant interferon-gamma and pentavalent antimony. AB - The clinical, parasitological, hematological, and serological evolution of visceral leishmaniasis in Brazilian patients was assessed during treatment with human recombinant interferon-gamma (rIFN-gamma; 0.1 mg/m2 i.m. days 1-14) followed by pentavalent antimony (Sbv; 10 mg/kg days 22-28). At day 30, 6 patients had improved, 2 had slightly improved, and 1 patient had deteriorated. IFN-gamma was well tolerated in the dose tested and may be very effective as an adjunct to conventional therapy with antimony. PMID- 8454910 TI - Interferon action: cytoplasmic and nuclear localization of the interferon inducible 52-kD protein that is encoded by the Ifi 200 gene from the gene 200 cluster. AB - Recently, we reported that an interferon (IFN)-inducible, murine 72-kD phosphoprotein (the 204 protein) that is encoded by the Ifi 204 gene from the gene 200 cluster is localized in the nucleolus and the nucleoplasm. We have now raised a polyclonal antiserum against the 202 protein that is encoded by the Ifi 202 gene from the same gene cluster and regions of which are homologous to those from the 204 protein. Using the antiserum, we established that the 202 protein is a 52-kD phosphoprotein whose level in cells from various murine lines can be increased up to 16-fold upon treatment with IFN-alpha. Experiments involving fractionation of cell lysates and indirect immunofluorescence microscopy of cultured cells revealed that the 202 protein was localized in the cytoplasm and the nucleus. Upon treatment of cells with IFN, the 202 protein first accumulated on the surface of a cytoplasmic, membranous fraction and after prolonged treatment with IFN it was localized mainly in the nucleus. In IFN-treated mitotic AKR cells, the 202 protein was colocalized with chromosomes. 202 protein extracted from IFN-treated AKR cells bound double-stranded DNA in vitro. Studies on 202 protein function should be facilitated by the availability of complete cDNA clones and the finding of cell lines and an inbred strain of mice in which the expression of this protein was impaired. PMID- 8454911 TI - Potentiation of interferon-alpha in vitro antiviral activity by interferon-gamma is not abrogated by antibody to interferon-gamma. AB - The addition of minute amounts of recombinant interferon-gamma (IFN-gamma) to recombinant IFN-alpha 2 significantly enhances its antiviral activity. Although this potentiating action of IFN-gamma is destroyed by treatment with acid, it is not significantly affected by treatment with antibodies to IFN-gamma, suggesting that IFN-gamma molecules can interact with cells to potentiate IFN-alpha activity, even in the presence of neutralizing antibodies. Implications of this phenomenon are multifaceted, including the possibility that other IFN activities can be altered synergistically by combinations of different IFN types, even in the presence of specific antibodies, which have been described to occur in vivo in several pathological conditions. PMID- 8454912 TI - 2',5'-Oligoadenylate synthetase activity as a responsive marker during interferon therapy for chronic hepatitis C. AB - The 2',5'-oligoadenylate (2-5A) synthetase is an intracellular enzyme induced by interferon (IFN). We evaluated the serum level of this enzyme in 25 patients affected by chronic hepatitis C and treated with recombinant IFN-alpha 2b. At the end of treatment, 14 patients were classified as responders and 11 as nonresponders. Before therapy initiation no significant differences in 2-5A synthetase levels among the patients were detected, while during therapy responders showed higher mean levels of 2-5A synthetase than nonresponders. An increase in the enzyme activity was observed after 1 month of therapy, and this trend was maintained in the following 2 months. The peak of 2-5A synthetase activity was found at the end of therapy. 2-5A synthetase levels were negatively correlated with serum alanine aminotransferase (ALT). This study suggests that 2 5A synthetase may be a useful marker to monitor IFN efficacy during treatment and to predict the clinical response. PMID- 8454913 TI - Effect of interferon-alpha 2a on malignant mesothelioma. AB - Malignant mesothelioma (MM) is a tumor that is resistant to conventional therapy. Interferon-alpha (IFN-alpha) has been used in the treatment of some human tumors, and we have previously demonstrated an in vitro anti-proliferative effect of IFN against MM cell lines. Therefore, the effect of recombinant human IFN-alpha (IFN alpha 2a) (Roferon-A, Hoffmann-La Roche) on previously untreated patients with MM has been studied. Twenty-five patients (24 male and 1 female), with a mean age of 59 +/- 9.9 years, were treated for 3 months with IFN-alpha 2a. The starting dose was 3 x 10(6) IU daily increasing to a maximum of 18 x 10(6) IU daily or as tolerated. All patients had measurable tumor on thoracic CT prior to commencement. CT scans were performed at 6 and 12 weeks to determine tumor response. Twenty patients completed 3 months of treatment. Five patients were withdrawn because of disease progression. Side effects were predictable and dose related. Dose reductions were necessary in 12 patients for grade 2 toxicity. One patient had a complete response (CR), 2 patients had partial responses (PR) (response rate = 12%), 13 (52%) patients remained stable, 1 of whom exhibited a delayed PR, and 9 (36%) had progressive disease. These data suggest that IFN alpha 2a is well tolerated in patients with MM and is active against MM in a proportion of patients. PMID- 8454914 TI - The pattern of lymph node involvement in carcinoma of the head of the pancreas. A histologic study of the surgical findings in patients undergoing extensive nodal dissections. AB - To clarify the pattern of lymph node metastasis in carcinoma of the pancreas, lymph node involvement was examined in forty-two patients who underwent extensive nodal dissections, including the paraaortic lymph nodes. The correlation between the spread of the tumor and lymph node involvement was evaluated: The most common site of involved lymph nodes was the retropancreatic region. The prevalence of nodal metastases was 78.6%. Metastases to the paraaortic region were present in seven patients, among whom metastases in the paraaortic region were most common in the median region from the celiac artery to the inferior mesenteric artery and in the space between the aorta and the vena cava. The risk of lymph node metastases tended to increase with tumor size, except in the paraaortic region, where the correlation between the frequency of metastasis and tumor size was poor. The probability of lymph node metastases increased with the degree of lymphatic invasion (ly) and the growth pattern of the tumor (INF) and was high in patients with invasion into the retropancreatic tissue and in tumors with scirrhous histology. These results indicate that even in small cancers, lymph nodes of the paraaortic region frequently harbor metastases and should be dissected en block during radical resections of pancreatic cancer. PMID- 8454915 TI - The influence of bile acids on the regulation of exocrine pancreatic secretion and on the plasma concentrations of neurotensin and CCK in dogs. AB - The influence of the intestinal bile acid content on the secretion of the exocrine pancreas and on the plasma concentrations of the relevant peptides (NT), and CCK is the subject of continuing controversy. Thus the alterations of pancreatic secretion and both hormones during variations of intestinal bile acid content were investigated. Modified Herrera fistulas were implanted in six dogs for analysis of the pancreatic secretions. Intraduodenal application of taurocholate (1.8, 3.6, or 7.2 mM) led to a marked reduction of the pancreatic secretion as well as to a simultaneous decrease of NT and CCK release after stimulation by the intraduodenal instillation of a 20% lipid emulsion. (The integrated protein secretion decreased from 20.1 +/- 1.9 g to 15.2 +/- 1.6 g, NT release dropped from 4970 to 3050 pg/180 min, and CCK from min.) cholestyramine together with the lipid emulsion had the opposite effect. The pancreatic protein as well as NT and CCK release increased. It therefore appears that there is a negative feedback relationship between the postprandial intestinal bile acid content on the one hand, and the secretion of the exocrine pancreas and the regulatory peptides NT and CCK on the other hand. This relationship is independent of any interaction between pancreatic proteases and bile acids. PMID- 8454916 TI - Newly established human pancreatic carcinoma cell lines and their lectin binding properties. AB - Two human pancreatic carcinoma cell lines, designated HuP-T3 and HuP-T4, were established from the ascites of pancreatic cancer patients with carcinomatous peritonitis. The cell lines were grown in monolayer cultures and had population doubling times of 38.6 and 37.1 h, respectively. HuP-T4 secreted large amounts of CEA and CA19-9 into the medium, and HuP-T3 produced a small amount of CEA, but no CA19-9. Both cell lines showed tumorigenicity in nude mice. Histologically, the HuP-T3-derived tumor was poorly differentiated adenocarcinoma, and the HuP-T4 derived tumor was well differentiated papillotubular adenocarcinoma. In lectin histochemistry at both light and electron microscopic levels, the most striking difference between the lectin binding properties of the two cell lines and those of control normal pancreatic ductal cells was that soybean agglutinin (SBA) bound to both cell lines, but not to controls. These newly established cell lines should be useful models that will contribute to clarifying the biological and biochemical characteristics of pancreatic cancer. PMID- 8454917 TI - Differential effect of submandibular gland resection on the growth of pancreatic cancer in cheek pouch and subcutaneous tissue. AB - Exogenous administration of epidermal growth factor (EGF) enhances tumor growth of H2T, a hamster pancreatic cancer that is inoculated in the cheek pouch. The effect of endogenous EGF on tumor growth, however, is not known. The main source of EGF in the body is the submandibular glands. This study examined the influence of submandibular gland resection (SMx) on H2T tumor growth in the cheek pouch and compared it to the growth in SC tissue. Bilateral SMx or sham operation was performed on male Syrian golden hamsters. In 30 hamsters (n = 15 for each operation group), 5 x 10(4) and 5 x 10(5) H2T cells were inoculated in the bilateral cheek pouches and intrascapular SC tissue, respectively (Exp. 1). In another 30 hamsters (n = 15 for each operation group), 5 x 10(5) and 1 x 10(6) H2T cells were inoculated at the same sites (Exp. 2). Two longest perpendicular diameters of the tumor were measured once a week for 12 wk (Exp. 1) or 8 wk (Exp. 2), and the tumor area was calculated. The tumor area in the cheek pouch became significantly smaller in the SMx group than the sham-operated group after the 8th wk (Exp. 1) or the 7th wk (Exp. 2). On the other hand, the tumor area in the SC tissue did not show any difference between groups through the experiments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454918 TI - The immunohistochemical evaluation of PSP/reg-protein in normal and diseased human pancreatic tissues. AB - In order to elucidate the characteristics of reg-protein, which is identical to pancreatic stone protein (PSP/reg-protein), and the relationship between the generation and evolution of chronic pancreatitis and the expression of PSP/reg protein in the pancreas, we investigated the expression of PSP/reg-protein in normal and diseased human pancreatic tissues by immunohistochemistry. The PSP/reg protein was expressed in all cases with normal pancreas or chronic pancreatitis, and in 70.6% of cases with pancreatic cancer. This protein was present in the cytoplasm of acinar cells and, in some cases, in the intraluminal contents of ductules in nonmalignant tissues. From the view of distribution and cellular localization, PSP/reg-protein was expressed more broadly and densely in chronic pancreatitis with mild to moderate injury than in the normal pancreas. However, the protein was less expressed in severely damaged chronic pancreatitis tissue, such as calcifying pancreatitis, than in the normal pancreas. These findings suggest that mild to moderate injury to pancreatic tissue may stimulate the synthesis of PSP/reg-protein, whereas more severe injury tends to depress it. PMID- 8454919 TI - [A radiological study of the hip joint in cerebral palsy]. AB - In cerebral palsy (CP), abnormal posture, contracture of the hip and dislocation occur during a long period of the course. In order to clarify the factors of tendency to dislocation, radiological survey was undertaken for the patients of CP. These data were analyzed from the respects of weight bearing, position of leg and developed deformity at the neck of the femur. One hundred seventy eight hips of 90 patients with an average of 26 years of age and 64 hips of normal individual as a control. Kai's method was used for measuring angles of tilting at neck and anteversion. The incidence of dislocations of the hip joints was more frequent in patients who were incapable of weight bearing than in patients who were capable of weight bearing (p < 0.01). However, there was no difference between spastic type and athetotic type of CP. In patients who were incapable of weight bearing inclination (the neck-shaft angle), anteversion of the femoral neck to the shaft showed larger than in patients who were capable of weight bearing (p < 0.01). Anteversion of patients who were capable of weight bearing of CP was larger than that of the normal control (p < 0.01), but extent of inclination was the same. From these findings the present investigator has concluded that femoral neck becomes valgus with an increased anteversion in longstanding CP patients who are especially unable to stand or walk. Furthermore, such hip joints are found to dislocate easily if adducted. PMID- 8454920 TI - [Diagnosis and treatment of fractures of the pelvis]. PMID- 8454921 TI - [Sarcoma related genes in bone soft tissues]. PMID- 8454922 TI - [A clinical multivariate study on bone change after parathyroidectomy in patients with renal osteodystrophy]. AB - This study investigated the changes of bone lesions after parathyroidectomy (PTX) in patients with renal osteodystrophy. Fifty-eight patients (mean age 43.7 +/- 8.4 years and mean duration of hemodialysis 120.9 +/- 32.1 months), who were resistant to medical treatments, were studied. Total PTX was followed by massive administration of alfacalcidol on these patients. The clinical symptoms, hematological findings, radiographic findings and second metacarpal bone density during the first 2 years following PTX were studied. After the operation, the clinical symptoms, hematological findings as well as radiographic findings improved in all of the patients and the density of the second metacarpal bone increased in 37 out of 40 patients. From these results we concluded that total PTX followed by massive administration of active vitamin D was effective in improving bone lesions and bone mineral density on patients with renal osteodystrophy. PMID- 8454923 TI - [Reconstruction for malignant bone tumor defects by a composite graft--plasty of the bone defect not involving a joint]. AB - Malignant bone tumors excluding joints of six patients were resected. The resultant bone defects were reconstructed with a synthetic fabric-enveloped hydroxyapatite spacer in five cases and a filler in one. Dacron fabric was used in four cases and each of Marlex mesh and Dexon mesh were used in one. The grafting and reconstruction processes were studied clinically and roentgenographically. CT scan was used in one case. The synthetic fabrics were helpful in repairing released supporting soft tissue by serving as a scaffold for the formation of new connective tissue. The spacer to the supporting soft tissues was biologically fixed. The synthetic fabrics were capable of inducing and supporting of the ingrowth of vascular connective tissue. The anchor of reconstructed supporting soft tissue became increasingly strong as time passed. For lasting and stable reconstruction, the spacer must be made uniform with the remaining bone by making an extracortical bone bridge using an autogenous bone graft. In two cases, autogenous bone grafts were taken from the ilium to bridge the remaining bone. The autogenous bone grafts were fixed to the spacer by enveloping the bone graft and the spacer with Marlex mesh and Dexon mesh. In the Marlex case roentgenographic findings showed that extracortical bone bridging was completed within six months after the operation. In the Dexon mesh case, extracortical bone bridging was not completed at one year after the operation, however the repair of the released supporting soft tissues was satisfactory. In order to avoid complications, a fabric must be absorbed fully after completion of the biologic fixation and extracortical bone bridging. Yet, further investigations are required to determine which of the synthetic fabrics and mesh sizes to enhance incorporation of the bone graft. PMID- 8454924 TI - [Posterolateral rotatory instability of the elbow--a case report and anatomical study of the lateral collateral ligament]. AB - A 20-year-old woman was referred to our clinic complaining of recurrent subluxation of her right elbow. A posterolateral rotatory instability test revealed that she had insufficiency of the lateral collateral ligament. She was surgically treated; the ligament was reconstructed by using the palmaris longus tendon. A year after operation, she had no pain in her elbow, and regained full range of elbow motion. The function of the lateral collateral ligament is often overlooked. We, therefore, dissected 24 elbow joints and studied anatomically in order to confirm the origin and insertion of the lateral collateral ligament. The ligament originates from the lateral epicondyle, and runs distally in fan shape. It further inserts partly to the annular ligament and partly to the supinator crest. After complete sectioning of the ligament, the forearm was fixed in supination, then flexed with valgus moment. This maneuver elicited subluxation of the radio-humeral joint, which was similar to what we observed in the clinical case. From these observations, we have concluded that the ligament is important for stability of elbow joint as well as the medial collateral ligament. PMID- 8454925 TI - [Informed consent in orthopedic surgery]. AB - Twenty-eight patients who had total joint replacement (TJR) and twenty-eight patients who sustained open reduction for fracture within or close to the joint were studied to determine their recall of the informed consent procedure. The questionnaire covered a postoperative time range of more than 5 months and less than 6 years (average: 2 years and 4 months). The patient's recall and the doctor's document of informed consent were scored 4 points for diagnosis and treatment, 1 point for prognosis, 3 points for benefits, 4 points for complications and 1 point for alternatives with a total of 13 points. In TJR, the average recall and document score were 8.6 points and 6.5 points respectively; and in fracture, 6.6 points and 4.9 points. Fifty-seven per cent of the patients with TJR recalled the risk of infection; and 54 per cent recalled the problem of loosening. Twenty-nine per cent of the patients with fracture recalled the risk of infection, and 29 per cent the risk of nonunion. In TJR, the recall score was related to the patient's age and the document score. There was significant difference in document scores among doctors. As a result of this study, standard documents for informed consent in each operation have been compiled with the aid of a word-processor to improve the quality of informed consent. PMID- 8454926 TI - [Measurements of bone mineral density of lumbar vertebrae in the lateral projection by dual-energy X-ray absorptiometry--comparison with anteroposterior spinal and radial bone mineral measurements]. AB - Bone mineral density (BMD) of lumbar vertebral bodies in the lateral projection were evaluated using dual-energy X-ray absorptiometry (DEXA) with respect to reproducibility of spinal bone measurements in two projections in healthy men, age-related bone mass changes in healthy women, and the bone mass in osteoporotic women. The BMD of the third lumbar vertebral body in the lateral projection (L3 LAT-BMD) and of the entire third lumbar vertebra in the anteroposterior projection (L3-AP-BMD) were measured with DEXA. The BMD of the distal metaphysis and distal diaphysis of the left radius were measured by single photon absorptiometry. The coefficient of variation in six men aged from 24 to 28 years was 1.7% for L3-LAT-BMD and 1.8% for L3-AP-BMD. In 82 healthy women ranging from 26 to 69 years of age (mean 50 years), BMD decreased rapidly after 50 years of age and above at all measured sites. However L3-LAT-BMD value showed wide distribution and decreased at an earlier age. Correlations within the two BMD values in the same bones were high (r = 0.799 for the vertebra and 0.803 for the radius), while those for any two BMD parameters for different bones were relatively low, with r values varying from 0.456 to 0.560. In 22 women with involutional osteoporosis ranging from 54 to 75 years of age (mean 65), values for L3-LAT-BMD and BMD of the distal metaphysis of the radius were lower than values predicted based on BMD of healthy women.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454927 TI - [Study on the intraneural topography of the brachial plexus]. AB - An accurate intraneural topography of the nerve fascicules in the brachial plexus provides a correct diagnosis and proper treatment of brachial nerve injuries. Four specimens of the branchial plexus were harvested from human cadavers by careful dissection and serially cross-sectioned from the nerve root level to the peripheral nerve. A spatial relationship between each nerve fascicule was observed and traced proximo-distally with a stereoscopic microscope. The main results and conclusions are as follows: 1. Four types of normal variation were identified in the composing elements of the brachial plexus. It is special interest to note the one in which both the fifth and sixth cervical nerve roots are composed of the dorsal scapular nerve. The existence of normal variations should be taken into account when determining the level and degree of branchial plexus injuries. 2. The nerve fascicules composing each peripheral nerve are most easily discerned at the cord level of the branchial plexus where there are no definite fiber exchanges between those nerve fascicules. These results would indicate that reconstructive nerve operations can be done successfully at the cord level or, at most, at the division level. PMID- 8454928 TI - [Iliac bone histomorphometry in women with hip fracture]. AB - A histomorphometric analysis was performed to evaluate the cancellous, endocortical envelope and cortical bone obtained at transiliac biopsy in 94 women with hip fracture (39 femoral neck and 55 trochanteric), aged 58-93 (mean 78.1 years), and 21 non-hip fracture women, aged 70-80 (mean 74.6 years), who underwent a bone biopsy during surgery on the hip or knee. In the cancellous envelope, bone volume, trabecular thickness and trabecular number was significantly lower in women with trochanteric fracture compared to the controls. These values were similar in women with femoral neck fracture and the controls. Eroded surface and osteoclast number at the endocortical envelope was significantly higher in both fracture groups than in controls. There were no differences in cortical thickness among the groups. The present study has concluded that trochanteric fracture is associated with low cancellous bone volume characterized by trabecular thinning and loss of trabecular plates and femoral neck fracture is not related with cancellous bone loss. Furthermore, in both fracture groups increased bone resorption at the endocortical envelope appears to be one of the important factors in cortical bone fragility. PMID- 8454929 TI - Immunohistochemical identification of muscle fiber types in normal and degenerated muscles. AB - Myosin ATPase reactions are generally used to differentiate between muscle fibers. However, those reactions have disadvantages including the need for delicate pH control and preincubation under non-physiological pH. Furthermore enzyme activity is only an indirect reflection of myofilament characteristics. In this study, an immunohistochemical method with anti-slow and anti-fast myosin heavy chain antibodies was used to observe: 1) whether muscle fiber types could be distinguished in degenerated muscles, 2) immunoreactivity of type 2C fibers in denervated muscles, and 3) discrepancies in structural disorders. Thirty one muscle biopsies which included neurogenic, myogenic, and control muscles were examined. Muscle fiber types were recognized in normal and in severely degenerated muscles. Type 2C muscle fibers were not necessarily constantly immunoreactive to both anti-slow and anti-fast myosin antibodies. In some targetoid fibers sites with absence of myosin ATPase activity had the same or rather higher immunoreactivity. Some muscle fibers undergoing fiber-type transformation showed discrepancies in reactivity between enzyme- and immuno reactivity. This immunohistochemical method is capable of observing changes of muscle fibers during denervation, reinnervation, and also sports activity. PMID- 8454930 TI - [An experimental study on the correction of scoliotic deformity--an application of the short segmental fixation system]. AB - The purpose of this experimental study is to seek a possibility if we could apply a short segmental fixation system for the correction of spinal deformity and keeping the moveability of the spine. We used 40 scoliotic rabbits in the experiment which were made after the Piggot's procedure. Apex of the curvature could be observed around T8 or T9. Ten of 40 rabbits were observed as a control group. On the other hand, the remaining 30 were used for an instrumentation group utilizing the short segmental fixation. Two complexes of T10-T11 and T12-L1 were made by mamillary process fixatives, bilateral small rods, wires and bone cement. The final magnitude of Cobb angle was 46.8 degrees on the average in the control group, and 14.8 degrees in the instrumentation group. In conclusion, short segmental fixation around the caudal area of the apex of the scoliotic curvature plays a major role in the correction of spinal deformity. PMID- 8454931 TI - [Proceedings of the 66th annual meeting of the Japanese Orthopaedic Association. Abstracts II]. PMID- 8454932 TI - Platelets, penicillins, and purpura: what does it all mean? PMID- 8454933 TI - Type II diabetes: who has the keys? PMID- 8454934 TI - Zidovudine therapy of HIV-associated thrombocytopenia: from MAIDS to AIDS. PMID- 8454935 TI - Impact of leukocyte adhesion on myocardial ischemia/reperfusion injury: conceivable mechanisms and proven facts. AB - Leukocyte activation, adhesion, and emigration serve a protective role during a well-contained inflammatory response. However, under certain pathologic conditions such as endotoxemia, inflammatory bowel disease, and ischemia reperfusion injury, leukocytes may turn against the host and aggravate--rather than prevent--tissue damage. Numerous experimental studies have been performed during the last decade to investigate the pathophysiologic role of leukocyte accumulation and adhesion during ischemia/reperfusion injury of various organs, in particular of the myocardium. Most of the latter studies investigated whether the consequences of experimental myocardial infarction could be attenuated by interventions aimed at the inhibition of chemotactic leukocyte infiltration or adhesion (or both) to microvascular endothelial cells. Although many promising results were reported, the consequent step towards an introduction of these strategies into experimental or even routine clinical management of patients with myocardial infarction has so far not been undertaken. In this manuscript, the authors try to give an overview on the state of the art of "antileukocyte" strategies in myocardial ischemia-reperfusion injury and to offer explanations for incongruent data obtained with diverse experimental approaches (animal species, treatment modalities, surgical and anesthesiologic artifacts, techniques for morphologic and functional evaluation of tissue damage). The authors conclude that long-term preclinical studies on suitable animal models, thoroughly investigating the positive and negative effects of antileukocyte interventions on the functional consequences of myocardial ischemia-reperfusion injury, are mandatory before the first clinical trial can be advocated. PMID- 8454936 TI - Penicillin-induced dysfunction of platelet membrane glycoproteins. AB - We examined the effects of the beta-lactam antibiotic penicillin G on platelet function and on specific membrane glycoproteins in vitro. Platelet concentrates exposed to 3 to 10 mmol/L penicillin for 48 hours showed irreversible inhibition of aggregation by thrombin in washed platelets after removal of the antibiotic. Although a brief 15-minute exposure to similar doses of penicillin also inhibited thrombin aggregation, the inhibition was reversed on removal of the penicillin by washing. Aggregation activity was also restored to normal levels by stimulation with high thrombin concentrations (> 0.4 U/ml). Results of the aggregation studies led us to examine how penicillin affects platelet membrane proteins. Membranes isolated after 48 hours of exposure of platelet concentrates to penicillin showed no differences from the control in total protein profiles on sodium dodecylsulfate--polyacrylamide gel electrophoresis or in the glycoprotein Ib or IIb content on immunoblotting. However, flow cytometric analysis with fluorescently labeled monoclonal antibodies revealed that exposure of platelets to penicillin for 15 minutes inhibited thrombin-induced modulations in the glycoproteins Ib, Ib-IX, IIb-IIIa, and P-selectin. These effects were observed with washed platelets and platelets in plasma. Penicillin also inhibited the regulation of expression of glycoproteins Ib-IX and IIb-IIIa in adenosine diphosphate--activated platelets. The inhibitory effects were partially reversed at high agonist concentrations. PMID- 8454937 TI - Insulin and IGF1 receptor function among type II diabetic responders and nonresponders to glyburide. AB - This study evaluated the insulin and insulin-like growth factor-1 (IGF-1) receptor function among patients with type II diabetes who did or did not respond to 1 month of treatment with the oral sulfonylurea agent glyburide. Patients with type II diabetes were initially placed on dietary treatment alone. Patients whose fasting plasma glucose level exceeded 9 mmol/L were enrolled in a prospective 1 month trial of oral glyburide. Clinical, laboratory, and receptor characteristics were assessed before and after glyburide therapy and were compared between the responders and non-responders as well as with matched nondiabetic control subjects. Of the 34 patients who participated in the study, 17 (50%) responded (fasting plasma glucose decreased to 7.8 mmol/L or by 30% from basal level) to the drug. There were no clinical parameters that could distinguish between patients responding and not responding to glyburide. Iodine 125-labeled insulin binding to intact erythrocytes tended to be higher among responders both before and after glyburide. However, the studies of specific insulin binding and insulin receptor tyrosine kinase activities of purified erythrocyte receptors could not distinguish between the two groups of patients with diabetes either before or after glyburide treatment. Compared with weight-matched nondiabetic controls, the erythrocyte insulin receptor tyrosine kinase activity in the patients with diabetes was significantly (by about 45%) decreased. Studies of the IGF-1 receptor likewise did not reveal differences between the two diabetic groups. In conclusion, one half of ambulatory patients with type II diabetes showed a satisfactory hypoglycemic response to a short-term glyburide treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454938 TI - Sustained elevation of platelet counts by long-term azidothymidine treatment of immunosuppressed mice. AB - Azidothymidine (AZT) has been demonstrated to increase platelet counts in patients suffering from acquired immunodeficiency syndrome (AIDS). However, the ability of long-term AZT treatment to sustain increases in platelet counts is controversial. We have recently demonstrated that AZT elevates the levels of circulating platelets in both normal C57BL/6 mice and mice made immunodeficient by infection with LP-BM5 murine leukemia virus (MAIDS mice). We therefore studied the effect of long-term AZT administration on platelet formation in both normal and MAIDS mice. Peripheral blood indices, levels of femoral and splenic megakaryocyte colony forming units (CFU-MK), and plasma levels of cytokines important in platelet formation-interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF)--were examined. Platelet counts remained elevated throughout a 120-day AZT treatment period. Splenic CFU-MK were not significantly changed in MAIDS mice, except at day 15 when they were elevated. Splenic CFU-MK were significantly decreased in normal mice at days 8 and 120, and increased at day 30. Bone marrow CFU-MK were increased by AZT treatment at all time points tested in both normal and MAIDS mice. Plasma levels of GM-CSF were unchanged by AZT treatment in both normal and MAIDS mice. Plasma levels of IL-6 were unchanged in AZT-treated normal mice but decreased in AZT-treated MAIDS mice. These results indicate that long-term AZT treatment maintains elevated levels of platelets in both normal and MAIDS mice and affects CFU-MK colony formation. Our studies add to a growing body of work suggesting that AZT can ameliorate thrombocytopenia associated with HIV disease. PMID- 8454939 TI - Role for mucous glycoprotein in protecting cultured rat gastric mucosal cells against toxic oxygen metabolites. AB - The gastric epithelium is exposed to oxygen radicals that are generated within the lumen. Much interest has been focused on the role of mucus in maintaining integrity of the gastric mucosa against oxidants, because gastric mucus may act as a scavenger of oxygen radicals. The aim of this study was to assess the role of mucous glycoprotein in protecting cultured gastric epithelial cells against oxygen radicals. Monolayer cultures of rat gastric mucus-producing cells were studied. Oxygen radicals were generated by hypoxanthine and xanthine oxidase. Cytotoxicity was quantified by measuring chromium 51 release form prelabeled cells. Rate of mucous synthesis was estimated by incorporation of tritiated glucosamine into the cells. The effects of tetraprenyl acetone (a stimulant of mucus production) and N-acetyl-L-cysteine (a mucolytic agent) on oxygen radical induced damage were determined. Preincubation with tetrapenyl acetone, while stimulating mucous glycoprotein by the cultured cells, caused a dose-dependent reduction of hypoxanthine-xanthine oxidase-induced 51Cr release, reaching maximum protection of the damage by 31% to 50%. In contrast, pretreatment with N-acetyl-L cysteine potentiated oxygen radical-induced 51Cr release dose dependently. The protective effect of tetraprenyl acetone was significantly abolished by N-acetyl L-cysteine. Neither tetraprenyl acetone nor N-acetyl-L-cysteine alone under the conditions of this study affected the cellular content of glutathione, which modulates oxygen radical injury to these cells. These results suggest that mucous glycoprotein partially but significantly protects cultured gastric epithelial cells against extracellularly generated oxygen radicals. It seems likely, therefore, that gastric mucus is involved in antioxidant defenses in these cells. PMID- 8454940 TI - Comparison of platelet membrane markers for the detection of platelet activation in vitro and during platelet storage and cardiopulmonary bypass surgery. AB - Changes in the platelet plasma membrane during activation were investigated by flow cytometry in a comparative study of in vitro platelet activation during platelet storage and cardiopulmonary bypass surgery. We studied changes in the expression of the plasma membrane glycoproteins lb and llla and CD31 antigen (PECAM-1), the alpha-granule membrane proteins GMP-140 (PADGEM, CD62 antigen) and GMP-33, and lysosomal integral membrane protein-CD63. A simultaneous change in the expression of the various glycoproteins induced by platelet activation was seen after thrombin stimulation in vitro and during platelet storage. Platelet activation in vivo in patients showed a more complex change in the expression of membrane glycoproteins. During cardiopulmonary bypass the mean fluorescence values for glycoprotein llla, GMP-33, and the percentage of GMP-140 and lysosome integral membrane protein-CD63 expressing platelets increased significantly. CD31 antigen expression was significantly decreased, whereas glycoprotein lb expression did not change. We conclude that flow cytometry is useful for the detection of changes in the expression of membrane glycoproteins induced by platelet activation in vitro and during platelet storage. Application of flow cytometry as clinical tool for screening platelet activation in patients or for identification of a prethrombotic state requires evaluation of a panel of platelet membrane glycoproteins because the changes in membrane expression may be different in various clinical situations. PMID- 8454941 TI - Catabolism of unglycated and naturally glycated forms of rabbit fibrinogen: their interaction with the healthy and deendothelialized aorta wall in normal and diabetic rabbits. AB - The incidence of nonenzymatic glycation of proteins within the hyperglycemic environment of diabetic plasma is increased compared with that in normal (i.e., nondiabetic) plasma. Whether glycation in vivo alters the behavior of proteins within the circulation is not well understood. Glycated fibrinogen, although not detected in normal rabbit plasma, was isolated from diabetic rabbit plasmas (glucose concentration 12 to 39 mmol/L) and separated from unglycated fibrinogen by boronate chromatography. The yield of glycated fibrinogen, which amounted to 3% to 6% of total fibrinogen, correlated with the content of plasma glucose. Glycated and unglycated fibrinogens facilitated aggregation of normal or diabetic platelets to a similar extent after adding adenosine-5'-diphosphate. Normal platelets stimulated by adenosine-5'-diphosphate bound more iodine 131-glycated fibrinogen than iodine 125-unglycated fibrinogen (p < 0.05), whereas the quantities of glycated and unglycated fibrinogens bound by diabetic platelets were not significantly different. When coinjected intravenously into normal or diabetic rabbits, 131I-glycated fibrinogen was cleared from the circulation faster than 125I-unglycated fibrinogen although the catabolic rates, measured as half-life, were not significantly different. At equilibrium, glycated fibrinogen was distributed significantly more in the extravascular and less in the vascular compartments of the normal and diabetic rabbit compared with the unglycated type. After balloon injury to the aorta in vivo, the unglycated/glycated ratio of radiolabeled fibrinogens associated with the platelet monolayer was 0.94, whereas for the damaged subendothelium the ratio was 1.20 (p < 0.005). We conclude that glycation in vivo changes several metabolic characteristics of fibrinogen in the normal and diabetic rabbit. PMID- 8454942 TI - Lazaroid antioxidant reduces incidence of diabetes and insulitis in nonobese diabetic mice. AB - Oxygen free radicals have been implicated as mediators of pancreatic islet beta cell damage in autoimmune, insulin-dependent diabetes mellitus (IDDM). We examined the effects of a potent antioxidant compound, U78518F, on the incidence of diabetes and pancreatic islet infiltration with lymphocytes and monocytes (insulitis) in the non-obese diabetic (NOD) mouse, an animal model for human IDDM. U78518F, administered to NOD mice from age 8 to 30 weeks, produced a dose dependent decrease in diabetes incidence, from 89% (16/18 control NOD mice) to 61% (11/18 NOD mice treated with 2 mg/kg/day U78518F, p < 0.05) and 44% (8/18 NOD mice treated with 16 mg/kg/day U78518F, p < 0.005). Protection against diabetes was associated with significant decreases in pancreatic insulitis and prevention of beta cell loss in the U78518F-treated NOD mice. These results suggest that antioxidants may have therapeutic application in attempts to prevent immune mediated islet beta cell damage and IDDM. PMID- 8454943 TI - Chloride alters renal blood flow autoregulation in deoxycorticosterone-treated rats. AB - Renal blood flow autoregulation was studied in deoxycorticosterone acetate (DOCA) treated rats. DOCA pellets (75 mg) were implanted in uninephrectomized rats, and the animals were then fed one of four diets: (1) normal sodium chloride level, (2) high in NaCl, (3) high in chloride, or (4) high in sodium. After 40 to 45 days of the DOCA-diet treatment, animals were subjected to renal blood flow autoregulation experiments; an inflatable aortic occluder was placed proximal to the renal artery, and renal blood flow (electromagnetic flow probe) was measured while renal perfusion pressure was reduced from normal (in that animal) to 20 mm Hg, in 10 mm Hg decrements to determine the lower threshold of autoregulation. Directly measured arterial blood pressure was higher in the DOCA-high NaCl group compared with the DOCA-normal NaCl group (127 +/- 3 mm Hg vs 103 +/- 4 mm Hg) during anesthesia. Significant elevation of lower autoregulatory thresholds were demonstrated in both the DOCA-high NaCl (98 +/- 7 mm Hg) and high chloride groups (94 +/- 3 mm Hg) compared with the DOCA-normal NaCl (77 +/- 4 mm Hg) and the DOCA high sodium (76 +/- 5 mm Hg). Pressure-flow curves of the DOCA-high chloride groups were shifted significantly downward (reduced renal blood flow at all pressures) and rightward (elevated lower threshold) compared with the DOCA-normal NaCl and -high sodium groups. These data indicate that DOCA-treated rats consuming a diet high in chloride have altered renal blood flow autoregulatory mechanisms. PMID- 8454944 TI - Regulation of lithium and boron levels in normal human blood: environmental and genetic considerations. AB - Blood lithium levels may be both genetically and environmentally regulated. The genetic component is evidenced mainly from studies in twins who were either normal or had a manic-depressive disorder. An environmental contribution is adduced from the relationship between the blood lithium level and the amount of the element ingested. No such information is available for boron, another element present in ultra trace amounts in human blood. Unusually high levels of lithium and boron in the waters of northern Chile offer an opportunity to study the genetic and environmental regulation of these elements in the blood of healthy subjects. Samples of blood (n = 40) and water (n = 47) were collected at seven locations in the province of Tarapaca. Most of the healthy subjects were Aymara who had been resident in the respective communities for at least 3 years. The samples were transported to Canada and then freeze-dried. Neutron irradiation was performed in a highly thermalized flux to induce the reactions 6Li (n, alpha) t and 10B (n,7Li) alpha. Assays of 6Li and 10B were conducted in a static mass spectrometer by measurement, respectively, of 3He, produced from decay of tritium, and 4He from alpha-particles. Lithium concentrations in water and blood exhibited a linear relationship, as did the boron concentrations in these fluids. Because some of the individual subjects (n = 15) were first-degree relatives, a genetic component to the regulation of blood levels was explored. The variance in blood levels of lithium and boron was significantly greater between than within families (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8454945 TI - Recombinant soluble IgA Fc receptor: generation, biochemical characterization, and functional analysis of the recombinant protein. AB - We previously described the cloning of a human myeloid cell surface receptor for the Fc region of immunoglobulin A (Fc alpha R). In the present study, a soluble version of the Fc alpha R (solFc alpha R) was generated by removing the transmembrane and cytoplasmic coding regions from full-length Fc alpha R cDNA and ligating into a mammalian expression vector. COS-7 cells transfected with the solFc alpha R plasmid secreted a protein that inhibited both immunoglobulin A (IgA) and anti-Fc alpha R monoclonal antibody (mAb) binding to Fc alpha R+ U937 cells. Furthermore, the solFc alpha R bound specifically to and could be eluted from an anti-Fc alpha R mAb-immunoaffinity column, retaining biological activity. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that the recombinant full-length Fc alpha R migrates over a molecular mass range of approximately 40-60 kd, consistent with the reported size and heterogeneity of the naturally occurring myeloid cell surface Fc alpha R. The solFc alpha R ran on SDS-PAGE as a smaller band (37-55 kd) that reduced to two bands of 23 and 25 kd following N-glycanase treatment, indicating that the Fc alpha R is a heavily glycosylated protein. The biochemical data, coupled with flow cytometry studies showing that the recombinant Fc alpha Rs bind to five different anti-Fc alpha R mAbs, clearly demonstrate that the cloned Fc alpha R corresponds directly to the major Fc alpha R species expressed on human monocytes, neutrophils, and myeloid cell lines. The generation of soluble receptor protein will permit investigations of the role of Fc alpha R in IgA mediated immunoregulation, effector functions, and disease. PMID- 8454946 TI - Interleukin-1-dependent mitogenic responses induced by protoscoleces of Echinococcus multilocularis in murine lymphocytes. AB - Mitogenic effects of protoscoleces (PSCs) of Echinococcus multilocularis on murine lymphocytes were studied. Spleen cells from normal BALB/c mice showed significant proliferative responses when cocultured with PSCs. Proliferative responses were observed in both the T and B cell populations. The PSCs also stimulated cells of the macrophage/monocyte lineage to secrete interleukin-1 (IL 1). Depletion of plastic- and Sephadex G-10-adherent cells from the spleen cell population significantly reduced the proliferative responses to PSCs and the low responsiveness was restored by addition of plastic-adherent cells to these cultures. Furthermore, addition of anti-IL-1 serum to the spleen cell cultures stimulated with PSCs completely suppressed the proliferative responses. These findings demonstrate that the mitogenic effect of PSC on lymphocytes depends on IL-1 secreted by cells of macrophage/monocyte lineage. PMID- 8454947 TI - Relationship between macrophage colony-stimulating factor production by uterine epithelial cells and accumulation and distribution of macrophages in the uterus of pregnant mice. AB - Estrogen and progesterone induce production of macrophage colony-stimulating factor (CSF-1) by uterine epithelial cells, and CSF-1 is produced in the uterus during pregnancy in mice. CSF-1 is a lineage-specific stimulator of macrophage proliferation, chemotaxis, and function. High concentrations of macrophages accumulate in the uterus during pregnancy. Experiments were conducted to determine whether a relationship exists between intrauterine CSF-1 production and the number and distribution of uterine macrophages during pregnancy in mice. The study demonstrated that on day 1 of pregnancy CSF-1 bioactivity levels were high. The number of macrophages in the uterus was also high on days 1 and 2, and macrophages were concentrated at epithelial surfaces. The decrease in CSF-1 bioactivity seen between days 1 and 2 was followed by a decrease in the macrophage concentration. An increase in CSF-1 bioactivity on day 4 was followed by an increase in the concentration of intrauterine macrophages. During the immediate postimplantation period, macrophages were detected primarily in the myometrium and deep endometrium and CSF-1 bioactivity was undetectable. During the second half of pregnancy, when CSF-1 concentrations were very high, the macrophage concentration was also very high and large numbers of macrophages were detected in association with epithelia. The data confirmed the existence of a direct relationship between intrauterine CSF-1 and macrophage accumulation and suggested that macrophages are attracted to epithelial surfaces by CSF-1. PMID- 8454948 TI - Macrophage phenotype regulation by colony-stimulating factors at bone marrow level. AB - Macrophages (m phi s) can be divided into several subpopulations, which differ in phenotype, function, and localization patterns. However, little is known about the mechanisms that regulate this heterogeneity. We investigated whether m phi heterogeneity is regulated by colony-stimulating factors (CSFs) at the bone marrow level. By clonal expansion of bone marrow-derived precursor cells in the presence of CSF-1, granulocyte-macrophage CSF or multi-CSF (interleukin-3), phenotypic heterogeneity was observed between m phi colonies. Heterogeneity was found especially when different CSF culture conditions were used but also between m phi colonies derived under the same CSF culture condition. Our results illustrate that CSFs from the bone marrow hemopoietic microenvironment are important for the induction of phenotypic heterogeneity within the progeny of cloned m phi precursor cells during maturation and differentiation in vitro. PMID- 8454949 TI - Characterization of neutrophil activation by repeated injection of endotoxin in rabbits. Role of neutrophils in the generalized Shwartzman reaction. AB - The relationship between activated neutrophils and end-organ injury in endotoxemia was studied. The function of peripheral blood neutrophils (PMNs) in rabbits with the generalized Shwartzman reaction (GSR) was compared to that of PMNs rabbits receiving a single injection of endotoxin. The following results were obtained: (1) PMNs from rabbits with the GSR demonstrated enhanced adherence to endothelial cells and increased mitochondrial ATP production; (2) the GSR did not enhance chemotaxis and oxygen radical production of PMNs; (3) a single injection of endotoxin did not cause necrosis of visceral organs; (4) in vitro detachment of endothelial cells by PMNs was increased in rabbits with the GSR; (5) in vivo administration of monoclonal antibody (mAb) against CD11b/CD18 (Mac 1) suppressed the increase in PMN adherence; and (6) hemorrhagic necrosis did not occur when mAb to Mac-1 was injected. Thus, enhanced adherence of PMNs to endothelial cells appears to play a key role in endotoxin-induced end-organ injuries in this animal model. PMID- 8454950 TI - Aspergillus fumigatus antigen induced eosinophilia in mice is abrogated by anti IL-5 antibody. AB - A murine model of allergic bronchopulmonary aspergillosis (ABPA), developed by exposure to Aspergillus fumigatus antigens, demonstrated eosinophilia of peripheral blood (PB), bone marrow (BM), and lung. The eosinophilia was abrogated by monoclonal anti-interleukin-5 (IL-5) antibody (TRFK-5) and not by an isotype control antibody (GL 113). Eosinophils in PB were enumerated from stained smears and their relative increase or decrease in cells from BM and lung was determined by an eosinophil peroxidase (EPO) assay (measured in optical density). Intraperitoneal injection of TRFK-5 in mice exposed to A. fumigatus antigen produced a significant reduction in eosinophils (PB 6.6 +/- 1.14% vs. 3.8 +/- 0.8%, P < .01) and EPO production in BM (0.935 +/- 0.03 vs. 0.615 +/- 0.02, P < .001). A similar reduction in EPO production in the lung (0.691 +/- 0.12 vs. 0.495 +/- 0.05, not significant) was also reflected in the histopathology for the different groups of mice. These findings confirming the role of IL-5 in eosinophilia, although not surprising, are significant in elucidating the immunopathogenesis of ABPA in the murine model. We conclude that in this model, eosinophilia may be due largely to the Th2 cytokine -IL-5 induced by A. fumigatus antigens. PMID- 8454951 TI - GTP-binding proteins in polymorphonuclear granulocytes of severely burned patients. AB - In order to study the biochemical mechanism underlying the cellular dysfunctions of polymorphonuclear granulocytes (PMNs) from severely burned patients, we analyzed the role of GTP-binding proteins (G-proteins) in PMNs from 11 burned patients. Our data demonstrate a significant enhancement of the basal GTPase activity within unstimulated neutrophils of severely burned patients compared to cells from healthy donors. This enhancement was significant within 4 weeks after the trauma, followed by a return to control levels. The increase in GTPase activity correlated with enhanced expression of the small G-protein Ras and the regulatory Ras-GTPase activating protein (Ras-GAP) compared to that in healthy donor cells. However, expression of the Ras-related protein Rap1, which is involved in initiation of the respiratory burst, was reduced. The observed changes in G-protein activity and expression impair the signal transduction cascade as well as bacterial killing and may lead to high susceptibility toward infections and finally to septic conditions. PMID- 8454952 TI - Bidirectional modulation of TNF-alpha production by alveolar macrophages in asbestos-induced pulmonary fibrosis. AB - Bronchoalveolar lavage (BAL) cells were isolated from rats 1, 3, and 6 weeks after a single intratracheal instillation of saline, UICC chrysotile asbestos (5 mg), or silica (5 mg). In asbestos-exposed rats, the pulmonary response was characterized by a significant increase in the number of alveolar macrophages (AMs) and the appearance of fibrotic lesions within 1 week. By contrast, mixed macrophage and neutrophil accumulations were observed in the silica group without evidence of fibrosis. Tumor necrosis factor-alpha (TNF-alpha) production by lipopolysaccharide (LPS)-stimulated BAL cells from asbestos-treated rats was significantly lower than controls 1 and 3 weeks after exposure. However, by 6 weeks higher levels of TNF-alpha production were noticeable in this group. Decreases in LPS-induced TNF-alpha production were also observed with BAL cells from silica-treated animals at all time points studied. Lower levels of TNF-alpha were not related to decreased BAL cell viability or the presence of a significant proportion of neutrophils in the silica group. Furthermore, biphasic changes in TNF-alpha production seen in the asbestos group were correlated with concomitant decreases (3 weeks) and increases (6 weeks) in levels of TNF-alpha mRNA in AMs. These data indicate that lower levels of TNF-alpha resulted from inhibition at the gene expression level and provide evidence for bidirectional modulation of TNF-alpha production by AMs during inflammatory reactions. PMID- 8454953 TI - Expansion of the liver-associated macrophage system in systemic lupus erythematosus-prone NZB/W mice. AB - Systemic lupus erythematosus is characterized by profound changes of the immune system. We report on alterations of the macrophage system in the murine NZB/W model of this disease. A greatly increased number of mature macrophages was isolated from the liver of NZB/W mice as compared to BALB/c mice and several other inbred strains used as healthy controls. In addition, the macrophage precursor compartment in the liver of NZB/W mice was expanded severalfold as measured by proliferation of light-fraction nonadherent nonparenchymal cells (NPCs) in response to colony-stimulating factors. Functional properties of the macrophages isolated from various anatomic sites of the lupus-prone mice were tested. Production of monokines by macrophages from liver, spleen, and peritoneal cavity, calculated on a per cell basis, was in the same range as in several healthy control strains tested. Yet the overall production of these immunoregulatory molecules by the increased liver macrophage system, the body's largest compartment of macrophages, is likely to result in increased levels of circulating monokines in the plasma of lupus-prone NZB/W mice. Indeed, significantly elevated levels of interleukin-6, interleukin-1, and colony stimulating activity could be demonstrated in the plasma of these mice both spontaneously and after stimulation with lipopolysaccharide. A possible contribution of the expansion of the macrophage system to the development of the disease is discussed. PMID- 8454954 TI - Distinct populations of antigen-presenting macrophages are required for induction of effector and regulatory cells in contact sensitivity response in mice. AB - Macrophages (Mf) and other antigen-presenting cells (APCs) are able to induce both immune and regulatory T cells. We compared the antigen-presenting activities of different subpopulations of thioglycolate-induced peritoneal macrophages from mice that were or were not treated with cyclophosphamide (CY) by several functional (adherence and phagocytosis) and morphologic (phenotypic) markers (FcR, Ia). Different subpopulations of macrophages were derivatized with trinitrophenyl and injected intravenously into recipients, which were tested directly for a contact sensitivity (CS) reaction or for the presence of efferent suppressor T (Ts) cells in passive transfer experiments. Our results demonstrate that peritoneal macrophages are both morphologically and functionally heterogeneous. Macrophages that induce immune cells that mediate CS have characteristics different from those that induce Ts cells. They accumulate in the low-density cell fraction on a discontinuous Ficoll gradient, are insensitive to treatment in vivo with low doses of CY, phagocytose poorly and adhere to plastic, and perhaps have low expression of FcRI and FcRII. Both macrophage fractions seem not to differ in expression of Ia, Mac-1, and Mac-3 antigens. It is argued that low doses of CY abrogate suppression in vivo by selective action on Ts cells. Our results confirm that at least a portion of the action of CY may be due to its influence on certain subpopulations of APCs. PMID- 8454955 TI - Differences in intracellular pool and receptor-dependent mobilization of the adhesion-promoting glycoprotein Mac-1 between eosinophils and neutrophils. AB - Recruitment of cells to an inflammatory site is a process that is selectively regulated. At an inflammatory site caused by bacterial infection, predominantly neutrophil accumulation is observed. This is in contrast to allergic inflammation, where predominantly eosinophil accumulation occurs. Mac-1 is an inducible adhesion molecule for both neutrophils and eosinophils. We examined the mobilization of this receptor on neutrophils and eosinophils after exposure to factors related to bacterial infections and allergic inflammation. We found more pronounced mobilization of Mac-1 on neutrophils than eosinophils after exposure to N-formylmethionyl-leucyl-phenylalanine, lipopolysaccharides, and activated sera (C5a). There was no significant difference in Mac-1 expression after exposure to aggregated immunoglobulin G. Incubation with interleukin-5 (IL-5) caused a significant increase of Mac-1 expression on eosinophils but not on neutrophils. Neutrophils seem to respond to a greater extent than eosinophils to factors related to bacterial infections, whereas eosinophils respond better to IL 5 associated with allergic inflammation. We measured the total pool of Mac-1 to evaluate whether these differences could depend on the size of the intracellular pool. Eosinophils had a larger total pool of Mac-1 than neutrophils. This finding increases the difference between eosinophils and neutrophils when relating the mobilized pool to the total pool. Stimulation with receptor-independent stimuli such as phorbol myristate acetate and ionomycin induced more pronounced mobilization of Mac-1 on eosinophils, but no differences were obtained if the mobilized pool was related to their total pool. These results indicate that the difference in responsiveness depends on different receptor-mediated signaling, since receptor-independent stimulation resulted in relatively similar mobilization of the intracellular pool of Mac-1. PMID- 8454956 TI - "Transitive inference" in multiple conditional discriminations. AB - We used multiple conditional discriminations to study the inferential abilities of pigeons. Using a five-term stimulus series, pigeons were trained to respond differentially to four overlapping pairs of concurrently presented stimuli: A+ B , B+ C-, C+ D-, and D+ E-, where plus and minus indicate the stimulus associated with reinforcement and extinction, respectively. Transitive inference in such situations has been defined as a preference for Stimulus B over Stimulus D in a transfer test. We measured this and other untrained preferences (A vs. C, A vs. D, B vs. E, etc.) during nonreinforced test trials. In three experiments using a novel, rapid training procedure (termed autorun), we attempted to identify the necessary and sufficient conditions for transitive inference. We used two versions of autorun: response-based, in which the subject was repeatedly presented with the least well-discriminated stimulus pair; and time-based, in which the subject was repeatedly presented with the least-experienced stimulus pair. In Experiment 1, using response-based autorun, we showed that subjects learned the four stimulus pairs faster than, but at a level comparable to, a previous study on transitive inference in pigeons (Fersen, Wynne, Delius, & Staddon, 1991), but our animals failed to show transitive inference. Experiments 2 and 3 compared time- and response-based autorun. Discrimination performance was maintained, but transitive inference was observed only on the second exposure to the response-based procedure. These results show that inferential behavior in pigeons is not a reliable concomitant of good performance on a series of overlapping discriminations. The necessary and sufficient conditions for transitive inference in pigeons remain to be fully defined. PMID- 8454957 TI - Selective associations produced solely with appetitive contingencies: the stimulus-reinforcer interaction revisited. AB - In studies reporting stimulus-reinforcer interactions in traditional conditioning paradigms, when a tone-light compound was associated with food the light gained stimulus control, but when the compound was paired with shock avoidance the tone gained control. However, the physical nature of the reinforcer-related events (food vs. shock) presented in the presence of the tone-light compound was always confounded with the conditioned hedonic value of the compound's presence relative to its absence. When the compound was paired with shock, its presence was negative relative to its absence (which was shock-free). In contrast, when the compound was paired with food, its presence was positive relative to its absence (which was food-free). The present experiment dealt with this confounding effect by conditioning a tone-light compound to be positive or negative, relative to its absence, solely with food reinforcement. One group of rats received food for responding in the presence of the tone-light compound and no food in its absence. The other group also responded in the presence of the compound, but received food only in its absence. These rats were trained on a chained schedule in which responding in the presence of the tone-light compound produced a terminal link signaled by the absence of the compound; responding ceased in the terminal link because it delayed food delivery. In a test session to assess stimulus control by the elements of the compound, tone and light were presented separately under extinction conditions. Rats that had been exposed to a positive correlation between food and the compound emitted almost double the responses in the presence of the light as in the presence of the tone. In comparison, rats that had been exposed to a negative correlation emitted only two thirds as many responses in the presence of the light as in the presence of the tone. Because this selective association was produced using only food, it appears that the contingencies under which a reinforcer is presented, rather than (or as well as) its physical properties, can generate the selective associations previously attributed to "stimulus-reinforcer interactions." This could mean that regardless of the class of reinforcer that ultimately maintains responding (appetitive or aversive), the contingency-generated hedonic value of the compound stimulus may influence the dominant modality of stimulus control. PMID- 8454959 TI - Acquisition of a spatially defined operant with delayed reinforcement. AB - Two experiments investigated the role of an immediate, response-produced auditory stimulus during acquisition, via delayed reinforcement, of a response selected to control for possible unprogrammed, operandum-related sources of response feedback. Experimentally naive rats were exposed to a delayed-food reinforcement condition, specifically a tandem fixed-ratio 1 differential-reinforcement-of other-behavior 30-s schedule. The response was defined as breaking a photocell beam located near the ceiling at the rear of the operant conditioning chamber. In Experiment 1, rates of photobeam breaking by each rat increased from near zero, regardless of the presence or absence of a tone that immediately followed the response initiating the delay interval. Though not essential, the tone facilitated response acquisition and resulted in more efficient response patterns at stability. Experiment 2 demonstrated that photobeam-breaking response rates under the delayed reinforcement contingency exceeded those in a preceding baseline condition in which no food was delivered. In addition, upon introduction of the delayed reinforcement procedure, correspondence between response patterns and the requirements of the reinforcement schedule increased over baseline levels in the absence of a food contingency. Together with a previous report of Lattal and Gleeson (1990), the present results suggest that response acquisition with delayed reinforcement is a robust phenomenon that may not depend on a mechanically defined response or an immediate external stimulus change to mediate the temporal gap between response and reinforcer. PMID- 8454958 TI - Effects of fixed and variable ratios on human behavioral variability. AB - The effect that ratio schedules of reinforcement had upon variability of responding was investigated in college students. Subjects were paid $0.02 contingent upon completion of eight presses, distributed in any combination across two push buttons; 256 different sequences were possible. Sequence emission was reinforced according to fixed- and variable-ratio schedules. Ratio requirements of 1, 2, 4 and 8 were presented in alternate components of a multiple schedule. The variability engendered by variable-ratio schedules was also compared to that engendered by fixed ratios. Variability increased with ratio size, irrespective of whether the schedule requirement was fixed or variable. The data demonstrate the similarity between the determinants of human and nonhuman variability, and they illustrate the role of ratio size in determining variability in operant behavior. PMID- 8454960 TI - Stock optimizing: maximizing reinforcers per session on a variable-interval schedule. AB - In Experiment 1, 2 monkeys earned their daily food ration by pressing a key that delivered food according to a variable-interval 3-min schedule. In Phases 1 and 4, sessions ended after 3 hr. In Phases 2 and 3, sessions ended after a fixed number of responses that reduced food intake and body weights from levels during Phases 1 and 4. Monkeys responded at higher rates and emitted more responses per food delivery when the food earned in a session was reduced. In Experiment 2, monkeys earned their daily food ration by depositing tokens into the response panel. Deposits delivered food according to a variable-interval 3-min schedule. When the token supply was unlimited (Phases 1, 3, and 5), sessions ended after 3 hr. In Phases 2 and 4, sessions ended after 150 tokens were deposited, resulting in a decrease in food intake and body weight. Both monkeys responded at lower rates and emitted fewer responses per food delivery when the food earned in a session was reduced. Experiment 1's results are consistent with a strength account, according to which the phases that reduced body weights increased food's value and therefore increased subjects' response rates. The results of Experiment 2 are consistent with an optimizing strategy, because lowering response rates when food is restricted defends body weight on variable-interval schedules. These contrasting results may be attributed to the discriminability of the contingency between response number and the end of a session being greater in Experiment 2 than in Experiment 1. In consequence, subjects lowered their response rates in order to increase the number of reinforcers per session (stock optimizing). PMID- 8454961 TI - The behavioral theory of timing: transition analyses. AB - Gibbon and Church (1990, 1992) have recently confirmed an important, parameter free prediction of the behavioral theory of timing (Killeen & Fetterman, 1988): The times of exiting from a bout of activity are positively correlated with the times of entrance to it. The correlations were slightly less than predicted, however, and the correlations between the start of an activity and the time spent engaged in that activity were negative, rather than zero. We adapted their serial model as an augmented (one-parameter) version of the behavioral theory, positing a lag between the receipt of a pulse from the pacemaker and transition into the next class of responses. The augmented version of the behavioral theory further improved the correspondence between the theory and the correlational data reported by Gibbon and Church. It also accounts for previously unpublished data from our laboratory derived from a new timing technique, the "peak choice" procedure. We show that the measured variance of movement times from one key to another closely approximates the estimated variance of transition times recovered from fits of the augmented model to the data. Such correspondence both attests to the correct identification of this source of variance and suggests ways to remove it, both from behavior and from our models of behavior. PMID- 8454962 TI - Automatic access of semantic information by phonological codes in visual word recognition. AB - An important issue in reading research is the role of phonology in visual word recognition. This experiment demonstrated that naming time of a target word (e.g., nut) is facilitated more by a homophone of a semantic associate (e.g., beach) than by a visually similar control (e.g., bench). However, this priming effect from the homophone obtained only when the prime word was exposed for 50 ms and was followed by a pattern mask and not when it was exposed for 200 ms before the pattern mask. In contrast, the "appropriate" prime (e.g., beech) provided facilitation at both exposure durations. Because the priming was obtained with a stimulus onset asynchrony of 250 ms, these data provide support for Van Orden's (1987) verification model, which posits that meaning is accessed through the automatic activation of phonological information. PMID- 8454963 TI - Episodic encoding of voice attributes and recognition memory for spoken words. AB - Recognition memory for spoken words was investigated with a continuous recognition memory task. Independent variables were number of intervening words (lag) between initial and subsequent presentations of a word, total number of talkers in the stimulus set, and whether words were repeated in the same voice or a different voice. In Experiment 1, recognition judgements were based on word identity alone. Same-voice repetitions were recognized more quickly and accurately than different-voice repetitions at all values of lag and at all levels of talker variability. In Experiment 2, recognition judgments were based on both word identity and voice identity. Subjects recognized repeated voices quite accurately. Gender of the talker affected voice recognition but not item recognition. These results suggest that detailed information about a talker's voice is retained in long-term episodic memory representations of spoken words. PMID- 8454964 TI - On the development of declarative memory. AB - In the visual paired-comparison task, which has been used to demonstrate memory abilities in human infants, Ss view pairs of pictures and then view new pictures paired with old ones. Memory is demonstrated when Ss spend more time looking at new pictures than at old ones. In a series of studies involving amnesic patients and normal Ss, the authors evaluated what kind of memory is exhibited in this task. The results suggest that performance ordinarily depends on the brain structures essential for declarative memory. These and other findings suggest that the visual paired-comparison test also depends on declarative memory when the task is given to human infants. Thus, successful performance on this task by infants probably reflects an early capacity for declarative memory. The relevance of these findings to the phenomenon of infantile amnesia is discussed. PMID- 8454965 TI - Effects of practice on component processes in complex mental addition. AB - Two experiments examined the effects of task practice on the speed of executing the component processes underlying the mental solution of complex addition problems. Componential analyses of Ss' response times in Experiment 1 demonstrated that the component process of carrying was reliably affected by amount of task practice. In contrast, the component processes of encoding single digits and of retrieving correct columnar answers from long-term memory appeared not to have been affected by amount of task practice. Computational feasibility checks indicated that the specificity of the practice effects could be explained by 2 distinct learning mechanisms: strengthening and composition. Results of Experiments 2A and 2B favor a composition explanation. We conclude that the differential practice effects in Experiment 1 are probably due to differential composition of component processes underlying complex mental addition. PMID- 8454966 TI - Units of knowledge in music performance. AB - The units of knowledge that form cognitive plans for music performance were examined in production errors. In Experiment 1, pianists performed multivoice homophonic music (containing strong across-voice associations) and polyphonic music (containing strong within-voice associations). Pitch errors reflected more chordal (across-voice) units in homophonic performances and more single-note units in polyphonic performances. Error instructions were harmonically and diatonically related to their intended pitches more often than chance, which demonstrates retrieval-based influences on planning. In Experiment 2, pianists conceptualized one of several voices as melody. Both the melody and the voice controlled by outer right-hand fingers (a common location of melody) contained fewer errors, which implies that there are conceptual, retrieval-based, and articulatory influences on units of knowledge that contribute to planning music performance. PMID- 8454967 TI - Memory biases in left versus right implied motion. AB - People remember moving objects as having moved farther along in their path of motion than is actually the case; this is known as representational momentum (RM). Some authors have argued that RM is an internalization of environmental properties such as physical momentum and gravity. Five experiments demonstrated that a similar memory bias could not have been learned from the environment. For right-handed S, objects apparently moving to the right engendered a larger memory bias in the direction of motion than did those moving to the left. This effect, clearly not derived from real-world lateral asymmetries, was relatively insensitive to changes in apparent velocity and the type of object used, and it may be confined to objects in the left half of visual space. The left-right effect may be an intrinsic property of the visual operating system, which may in turn have affected certain cultural conventions of left and right in art and other domains. PMID- 8454968 TI - Analysis of data. PMID- 8454969 TI - Computer-based medical records. PMID- 8454971 TI - Parity clarity: proposal for a new obstetric shorthand. PMID- 8454970 TI - Cryosurgery. PMID- 8454972 TI - Aeromedical transport. PMID- 8454973 TI - Estimated gains in life expectancy with use of postmenopausal estrogen therapy: a decision analysis. AB - BACKGROUND: Epidemiologic data are accumulating that suggest that postmenopausal estrogen therapy reduces the risk of developing coronary artery disease (CAD). Computer simulation by Markov analysis can be applied to current data to estimate the increase in life expectancy obtained from postmenopausal estrogen use and compare them with benefits from other therapies for CAD risk reduction. Decision analysis techniques can also examine whether the benefits of unopposed estrogen regimens ever exceed those of combination therapy. METHODS: In our analysis, hypothetical cohorts of postmenopausal women age 50 and 65 years with intact uteri were assigned either to estrogen and progesterone therapy or unopposed estrogens. The subjects were also defined by risk category for CAD. Outcomes were measured in terms of life expectancy for treatment cohorts compared with identical untreated cohorts. RESULTS: Life expectancy benefits in combined therapy groups were found to be very substantial for all CAD risk categories. Cohorts who began therapy at age 50 years showed benefits ranging from 0.3 years of additional life for those at low risk of developing CAD to 2.3 years for those at high risk. Even though the addition of progestins may theoretically result in reduction of overall CAD benefits, impressive gains in life expectancy were still found even when a 40% reduction in estrogenic effect was considered. Overall, benefits were very favorable when compared with other accepted strategies for CAD risk reduction. Little additional benefit was found to justify use of unopposed estrogens given the potential added mortality from endometrial cancer. CONCLUSIONS: Substantial increases in life expectancy may result from postmenopausal estrogen therapy. These may be equal to or possibly greater than benefits from other well-recognized risk-reduction strategies. Little advantage in additional life expectancy is found to justify use of unopposed estrogens. PMID- 8454974 TI - Magnetic resonance imaging use by primary care physicians. AB - BACKGROUND: Magnetic resonance imaging (MRI) has recently been introduced in the United States as an imaging technique for clinical use. Initially used by neurologists to view the brain stem, its indications have rapidly expanded to include spine, pelvis, bone marrow, and joints. This has raised concerns over the appropriate, cost-effective use of such an expensive technology. This paper examines MRI scanning patterns that have developed over time in central Massachusetts and surveys primary care knowledge, attitudes, and patterns of utilization. METHODS: The two MRI centers in central Massachusetts were surveyed for information about the number and types of scans ordered and the specialties of the physicians who ordered the scans. Questionnaires were sent to primary care physicians in Worcester County to assess knowledge and attitudes about MRI and utilization. RESULTS: The data demonstrate changing patterns of MRI utilization over time. Orthopedics has been the specialty with the greatest increase in use, now slightly surpassing neurology in the total number of scans ordered. Primary care physician use has doubled over this same period. Not all primary care physicians utilize MRI, but those who have used the technology have familiarized themselves with its indications and problems and have a better knowledge about its costs. CONCLUSIONS: Utilization patterns of MRI have changed considerably in a short time, with primary care physicians requesting use of this new technology much more frequently than when it was first introduced. PMID- 8454975 TI - Follow-up Papanicolaou smear for cervical atypia: are we missing significant disease? A HARNET Study. AB - BACKGROUND: The presence of cervical atypia on the Papanicolaou (Pap) smear may be an indicator of significant cervical disease. Many investigators recommend that colposcopy be performed in these women. We wished to determine the prevalence of undetected cervical intraepithelial neoplasia (CIN) among women identified as having cervical atypia by cytologic testing in a primary care setting. METHODS: Pap smears were performed on all women (N = 7458) attending six family practice offices for a health maintenance examination from August 1989 through February 1991. Cytologic specimens were obtained using an endocervical Cytobrush and wooden spatula. Consenting subjects with cervical atypia underwent repeat Pap smear testing immediately before a colposcopic examination after a 4- to 6-month waiting period. RESULTS: One hundred fifty-nine women identified as having cervical atypia consented to having a colposcopic examination. Of these, 96 (60%) demonstrated abnormalities on biopsy, including 40 with condyloma, 41 with CIN I, and 15 with CIN II to III. The false-negative rate of the follow-up Pap smear for detecting these cases of condyloma and CIN was 57%. CONCLUSIONS: One third of the women with cervical atypia identified on an initial Pap smear in this primary care community setting had CIN after colposcopic biopsy. The single follow-up Pap smear obtained with the endocervical Cytobrush and wooden spatula failed to detect one half of the cases of biopsy-proven CIN. Further studies regarding the use of additional screening methods for follow-up are necessary. PMID- 8454976 TI - Artificial neural networks for predicting failure to survive following in hospital cardiopulmonary resuscitation. AB - BACKGROUND: Neural networks are an artificial intelligence technique that uses a set of nonlinear equations to mimic the neuronal connections of biological systems. They have been shown to be useful for pattern recognition and outcome prediction applications, and have the potential to bring artificial intelligence techniques to the personal computers of practicing physicians, assisting them with a variety of medical decisions. It is proposed that such an artificial neural network can be trained, using information available at the time of admission to the hospital, to predict failure to survive following in-hospital cardiopulmonary resuscitation (CPR). METHODS: The age, sex, heart rate, and 21 other clinical variables were collected on a consecutive series of 218 adult patients undergoing CPR at a 295-bed public acute-care hospital. The data set was divided into two groups. A neural network was trained to predict failure to survive to discharge following CPR, using one group as the training set and the other as the testing set. The procedure was then reversed, and the results of the two networks were combined to form an aggregate network. RESULTS: The trained aggregate neural network had a sensitivity of 52.1% and a positive predictive value of 97% for the prediction of failure to survive following CPR. The relative risk of actually failing to survive to discharge following CPR for a patient predicted not to survive was 11.3 (95% CI 3.3 to 38.2). CONCLUSIONS: Predicting failure to survive following CPR is but one possible application of neural network technology. It demonstrates how this technique can assist physicians in medical decision making. Future work should attempt to improve the positive predictive value of the neural network, to consider combining it with an expert system, and to compare it with other predictive tools. Once validated, the network can be distributed as a separate application for use by practicing physicians. PMID- 8454977 TI - Continuous quality improvement for continuity of care. AB - BACKGROUND: Continuous quality improvement (CQI) techniques have been used most frequently in hospital operations such as pharmaceutical ordering, patient admitting, and billing of insurers, and less often to analyze and improve processes that are close to the clinical interaction of physicians and their patients. This paper describes a project in which CQI was implemented in a family practice setting to improve continuity of care. METHODS: A CQI study team was assembled in response to patients' complaints about not being able to see their regular physician providers when they wanted. Following CQI methods, the performance of the practice in terms of provider continuity was measured. Two "customer" groups were surveyed: physician faculty members were surveyed to assess their attitudes about continuity, and patients were surveyed about their preferences for provider continuity and convenience factors. RESULTS: Process improvements were selected in the critical pathways that influence provider continuity. One year after implementation of selected process improvements, repeat chart audit showed that provider continuity levels had improved from .45 to .74, a 64% increase from 1 year earlier. CONCLUSIONS: The project's main accomplishment was to establish the practicality of using CQI methods in a primary care setting to identify a quality issue of value to both providers and patients, in this case, continuity of provider care, and to identify processes that linked the performance of health care delivery procedures with patient expectations. PMID- 8454978 TI - Papanicolaou smear quality assurance: providing feedback to physicians. AB - BACKGROUND: The effective management of Papanicolaou (Pap) smears depends on the reliability and accuracy of obtaining and interpreting the specimen. Provider sampling error is one of the important factors contributing to inadequate specimens. Feedback on provider performance may be an effective way to improve the quality of Pap smears. METHODS: A pilot study in a university-based residency program involving resident and faculty physicians was initiated to assess the impact of feedback on performance of Pap smears. After establishing adequacy and inadequacy criteria and recording adequacy rates for 3 months, individual and group feedback was implemented. No formal educational intervention on Pap smear technique was undertaken. RESULTS: The quality of 836 Pap smears performed by 9 faculty and 13 resident physicians showed continued improvement in both sampling and slide preparation to 90% adequacy over a 9-month period. This improvement, though clinically useful, was not statistically significant owing to the relatively small numbers of smears performed by each physician. This form of feedback may be useful in both practice and educational settings. CONCLUSIONS: Feedback without any formal educational intervention led to a clinically useful trend of improvement in the quality of Pap smears, which has been sustained since the study began. This type of simple feedback may be useful in practice settings and particularly valuable in pinpointing areas for improvement for learners in residency programs. PMID- 8454979 TI - Air medical transport. AB - Emergency air medical transport has become an integral part of the practice of medicine. In 1990, there were more than 170 air medical programs in operation in the United States. The proper and safe use of air medical transport requires a basic understanding of the medical implications of flight and the capabilities and constraints involved in transporting patients by air. The purpose of this paper is to review this information and provide guidelines for the use of air medical transport. PMID- 8454980 TI - Psychiatry in 2001. AB - In the year 2001, the status of psychiatry is viewed through the experiences and thoughts of a hypothetical psychiatrist and a hypothetical family physician. Psychiatry is continuing its explosive progress in brain physiology and psychopharmacology, but has backed away from studies and practice in the psychosocial field. As practice patterns change and more outpatient psychiatric care falls into the purview of the family physician, the two physicians see a need for ever more collaboration between their specialties. A greater commitment by family medicine to psychosocial training and research, especially in areas such as physician-patient and physician-family relationships, is urged. PMID- 8454981 TI - The management of non-insulin-dependent diabetes mellitus in the elderly. AB - More than 8 million Americans are afflicted with non-insulin-dependent diabetes mellitus (NIDDM), a complex disease process characterized by insulin resistance and impaired insulin secretion. Diet and exercise continue to be the cornerstones of treatment. Most patients, however, require the addition of an oral sulfonylurea agent to achieve adequate glucose control. The second-generation sulfonylureas, glyburide and glipizide, are effective at lower doses and may have fewer adverse effects and drug interactions than the older, first-generation agents. For these reasons the second-generation sulfonylureas are preferred. Insulin therapy is required in patients with hyperosmolar state, infection, or other forms of stress, or in those who fail to respond to treatment with oral sulfonylurea. Some patients may benefit from the concurrent administration of insulin and an oral agent. Hypoglycemia is the greatest risk of drug therapy in elderly patients with NIDDM. This is especially true in elderly patients who are exquisitely sensitive to the effects of sulfonylureas and insulin. Treatment should, therefore, be initiated at very low doses and gradually adjusted. PMID- 8454982 TI - Mycobacterium marinum skin infections: two case reports. AB - Most infections of soft tissue injury sites are caused by Staphylococcus or Streptococcus and respond to beta-lactam antibiotics. Occasionally, a patient does not respond to routine antibiotics, and other possibilities must be considered. A detailed history of the event that caused the soft tissue injury can be important in the diagnosis. Two cases of Mycobacterium marinum soft tissue infection (ie, fish tank granuloma) are presented. PMID- 8454983 TI - Fluoxetine-induced SIADH: a geriatric occurrence? AB - After major depression was diagnosed in a 83-year-old woman, fluoxetine was prescribed. Six days later she became delirious and weak, necessitating hospitalization. She was found to have hyponatremia secondary to fluoxetine induced syndrome of inappropriate antidiuretic hormone secretion (SIADH). Recovery was complete after discontinuation of the medication. PMID- 8454984 TI - Tuberous sclerosis in early infancy: a case report. AB - The diagnosis of tuberous sclerosis in an infant was delayed by 3 months. Failure to take an adequate patient history because of a language barrier between parents and caregivers and to observe the classic stigmata of tuberous sclerosis contributed to the delay. A brief review of the case and the diagnosis of tuberous sclerosis is presented. PMID- 8454985 TI - Determination of the concentration of tetramethylenedisulfotetramine in human blood by GC/FPD. PMID- 8454986 TI - Military drug positive rates in the European Theater drug rates in Europe. AB - Urine samples were collected from Air Force and Army service members within the European Theater and analyzed for drugs of abuse employing radioimmunoassay and gas chromatography/mass spectroscopy (GC/MS). Data collected from January 1985 through December 1991 indicate that the total positive rate decreased from 4.67% to 0.69%. Of the drugs tested, tetrahydrocannabinol (THC) was the drug abused most in the European Theater during this time period. PMID- 8454987 TI - Efficacy of 1% sodium fluoride as a preservative in urine samples containing glucose and Candida albicans. AB - Whether urine samples used in forensic science DUI testing can be compromised by endogenous ethanol production is a recurrent and yet unresolved issue. This study first assessed unpreserved urine samples that were collected, processed, and analyzed repeatedly over 13 to 41 days using a standard gas chromatographic procedure for ethanol analysis. Despite extensive microbial growth, ethanol was not detected in any test sample. The extent of ethanol production in samples supplemented with glucose, Candida albicans, or both was determined to evaluate the potential for ethanol production in urine samples associated with pathological conditions such as urinary tract yeast infections and diabetes mellitus. Ethanol production under each of the above treatment conditions was assessed in the presence and absence of 1% sodium fluoride as a microbial suppressant. Mean ethanol concentrations were determined for unpreserved samples containing urine only (0.003 +/- 0.005 g%), urine plus yeast (0.006 +/- 0.009 g%) and urine plus glucose (0.067 +/- 0.070 g%). Unpreserved samples supplemented with both yeast and glucose attained mean ethanol concentrations of 0.164 +/- 0.057 g% (P < 0.01). Ethanol could not be detected in any corresponding duplicate samples, which were preserved with 1% sodium fluoride. A lack of ethanol production in any of the unpreserved urine samples indicates that false DUI convictions due to endogenous ethanol production are very unlikely. And while endogenous ethanol production is possible in the presence of both glucose and contaminating C. albicans, 1% sodium fluoride completely eliminated microbial fermentation. PMID- 8454988 TI - Analysis of phencyclidine and cocaine in human hair by tandem mass spectrometry. AB - A confirmation procedure for the analysis of cocaine, benzoylecgonine, ecgonine, and phencyclidine (PCP) in human hair using tandem mass spectrometry has been developed. This procedure requires no solvent extraction and thus can examine the metabolites of drugs such as cocaine. Hairs from six cocaine users were examined and the amount of cocaine and its ratio to the metabolites was not correlated to the reported use pattern. Only PCP was detected in the hair from a PCP user, no metabolites were found. In passive exposure experiments, hair was found to tightly absorb PCP from aqueous solutions, which mimics the incorporation of PCP by the body. These results indicate that drugs may be absorbed onto the hair of nonusers and become tightly bound. PMID- 8454989 TI - The effect of food on alcohol absorption and elimination patterns. AB - The same nine subjects (six male, three female) were given near bolus doses of alcohol (0.69 g/kg) on two occasions separated by one week. They were instructed to consume the alcohol as rapidly as possible (12.1 min average). The alcohol was consumed after dilution to 15% with fruit punch mix. Both phases of the experiment were conducted in a similar manner with the exception of stomach condition. In Phase I the alcohol was consumed immediately after a large meal. In Phase II, the alcohol was consumed after an approximate 6 h fast. An Intoxilyzer 4011A was used to measure Breath Alcohol Concentration (BrAC), beginning immediately after the alcohol was consumed and ending approximately 4 h after the end of drinking. The BrACs were measured in grams per 210 L of breath, at approximate 8 min intervals over the course of the experiment. The alcohol absorption and elimination curves were plotted and evaluated for each subject in both experiments. The average time required to reach maximum BrAC was 41 min for both empty and full stomach conditions. The average elimination rate of ethanol was found to be significantly lower after meal (0.017 BrAC/h compared to 0.020 BrAC/h) but the time required to reach zero BrAC was not significantly different (5.01 h full stomach, 5.05 h empty stomach). PMID- 8454990 TI - A computerized neural network method for pattern recognition of cocaine signatures. AB - This article describes a practical procedure for rapidly searching a large database of cocaine signatures to identify database entries that closely resemble a given reference cocaine exhibit using a personal computer (PC). The procedure takes advantage of the pattern recognition capability of the multilayer perceptron neural network to identify similar cocaine signatures. A PC-based software implementation is now being used on a daily basis at the North Carolina State Bureau of Investigation (NCSBI) to aid forensic experts in identifying signatures that originate from the same batch. Intelligence reports generated from database searches have been useful to undercover agents in the field who are striving to build drug related conspiracy cases. This software was developed as a collaborative effort between the NCSBI and the Center for Systems and Engineering of the Research Triangle Institute. PMID- 8454991 TI - Preliminary observations of the effects of amitriptyline in decomposing tissues on the development of Parasarcophaga ruficornis (Diptera: Sarcophagidae) and implications of this effect to estimation of postmortem interval. AB - Larvae of Parasarcophaga ruficornis (Fabricius) (Diptera: Sarcophagidae) were reared on tissues from rabbits administered different dosages of amitriptyline to study the effects of this drug on the development of this insect species. The rabbits were given 300, 600, and 1000 mg of amitriptyline via ear vein infusion. No significant differences in rates of larval growth were observed among the colonies. Durations of the larval stage were significantly longer for larvae fed on tissues from rabbits receiving amitriptyline. Larval mortality was observed to be 5.5% for the control colony, but ranged from 40.5 to 57.5% for the test colonies. Durations of the puparial stage were significantly longer for the colonies fed on tissues from the rabbits receiving the 600 and 1000 mg dosages of amitriptyline than for the control and colony fed on tissues from the rabbit receiving the 300 mg dosage. Observed differences in the durations of the larval and pupal stages from the test colonies were sufficient to alter a postmortem interval estimate by up to 77 h, if based on normal developmental patterns for this species at 26 degrees C. Presence of amitriptyline and nortriptyline could be detected in larvae from all colonies fed on tissues from the rabbits receiving amitriptyline using high-performance liquid chromatography (HPLC). PMID- 8454992 TI - Characteristic features of entrance wounds from hollow-point bullets. AB - Several cases of gunshot wounds produced by hollow-point bullets showed characteristic central tags. These apparently arise from sparing of the skin surface by the hollow point cavity when the bullet strikes the skin tangentially. This unique feature may be helpful in assessing entrances of perforating wound tracks or other cases where the bullet is either not available or unknown. PMID- 8454993 TI - Detection of fatal therapeutic misadventures by an urban medico-legal system. AB - Very few population-based studies have evaluated fatal therapeutic misadventures, in particular the adequacy of their detection. We therefore assessed the adequacy of the reporting and detection of fatal therapeutic misadventures in an urban setting medico-legal system. The coroner's files and the related hospital records were reviewed as to the circumstances of the incidents and the adequacy of notification by the care providers in Allegheny County, Pennsylvania, for the period of January 1, 1982 through December 31, 1991. The annual average rate of fatal misadventures was 2.2 per 100,000 hospital admissions or 4.7 per million inhabitants (total 63 cases). The survival time from the occurrence of the misadventure was within 24 h in 60% of the cases. University-related hospitals had double the rate of misadventure fatalities (118.2 per 100,000 beds per year), compared to that in community-based hospitals (53.9 per 100,000 bed per year). In more than half of the cases, the hospitals reported the incidents within an hour from the pronouncement of death, 28.6% within 5 h, and 19% after more than 5 h. In 10 cases (15.9%), the notification by the hospitals was clearly deficient in determining the manner of death. In a few cases, the incident was initially reported by the relatives, by the hospital pathologists, or by the media. A high likelihood of under-reporting of fatal misadventures to the medico-legal system is substantiated by comparing with the results reported by others. The possible measures to increase the monitoring and reporting, and to reduce the related mortality are further discussed. PMID- 8454994 TI - Atypical gunshot exit defects to the cranial vault. AB - Cranial exit wounds typically display external beveling, however, variation has been noted in the literature due to keyhole phenomena and pre-existent fractures. Two cases of atypical exit morphology are presented with features mimicking blunt trauma. In both instances radial fractures created by the exiting impact allowed passage without producing exit beveling. A working knowledge of the biomechanics of bone fracture, radiographs and low power microscopy are essential elements for the proper interpretation of such exit wound fractures. PMID- 8454995 TI - Asphyxial deaths due to hanging in children. AB - A review of the records for five years from the Coroner's Offices of Marion County, Indiana and Franklin County, Ohio, which have a combined population of 2.4 million, yielded 12 cases of hanging deaths in children 13 years of age or younger. The age range was 2 1/2 to 13 years and only two of the 12 victims were female. There were three unequivocal suicides, five accidental deaths and four cases where, despite extensive investigation, the manner of death remained undetermined. The scene and autopsy findings are presented and the cases discussed with regard to determination of manner of death. Additionally, the significance and pathophysiology of petechiae are discussed. PMID- 8454996 TI - Deaths caused by lightning. AB - Though a rare cause of death, lightning is reported to be responsible for more fatalities each year in this country than any other type of natural disaster. Lightning injuries differ significantly from other high voltage electrical injuries because of the high current flow, but extremely short duration, of the lightning stroke. We present a series of cases over the period of 1985 to 1991 in Cook County, Illinois in which lightning was the direct cause of death. Our discussion reviews the nature of lightning, the effects it may have on humans, and the ways in which deaths due to lightning might be prevented. PMID- 8454997 TI - Autoerotic fatalities with power hydraulics. AB - We report two cases in which men used the hydraulic shovels on tractors to suspend themselves for masochistic sexual stimulation. One man developed a romantic attachment to a tractor, even giving it a name and writing poetry in its honor. He died accidentally while intentionally asphyxiating himself through suspension by the neck, leaving clues that he enjoyed perceptual distortions during asphyxiation. The other man engaged in sexual bondage and transvestic fetishism, but did not purposely asphyxiate himself. He died when accidentally pinned to the ground under a shovel after intentionally suspending himself by the ankles. We compare these cases with other autoerotic fatalities involving perceptual distortion, cross-dressing, machinery, and postural asphyxiation by chest compression. PMID- 8454998 TI - The A.B.F.O. study of third molar development and its use as an estimator of chronological age. AB - Radiographs depicting third molars (M3s) have been used to estimate chronological age in juvenile and adult suspects, but accuracy of the method has been in question. This study provides age benchmarks for American whites (age range: 14 to 24 years) based on cases (n = 823) drawn from diplomates of the American Board of Forensic Odontologists in the United States and Canada. Maxillary M3 formation was slightly advanced over mandibular M3s, and root formation occurred earlier in males than females. Mean and median ages for M3 formation are tabled using Demirjian's eight-grade classification. Regression formulas and empirical probabilities are provided relative to the medicolegal question of whether an individual is at least 18 years of age. The M3 is the most variable tooth in the dentition, but situations arise where M3 formation is the only usable datum for age estimation. PMID- 8454999 TI - Theoretical difficulties in the treatment of mentally ill prisoners. AB - Work as a psychiatrist in a correctional setting involves a difficult interface of the theories of psychiatry, the law, and corrections. The coexistence of models of punishment, rehabilitation and mental health treatment in this work create ethical and practical challenges for the psychiatrist. The lack of a singular or clear theoretical framework may contribute to a potential for countertransference issues to play a determinant role in psychiatric decisions. These difficulties are based on the intersection of the theoretical issues involved. PMID- 8455000 TI - A comparison of sexual victimization in the childhoods of pedophiles and hebephiles. AB - The association between perpetration of sexual abuse and the offender's own victimization as a child has been well documented in the literature. Various researchers have examined this relationship by assessing the exclusiveness of the sexual abuser's behavior, the gender of his victims and the gender of his own childhood abuser. This study was designed to assess the differences between pedophiles and hebephiles in features of their own childhood victimization. Subjects were 135 pedophiles and 43 hebephiles who admitted to their offences. A total of 42% of pedophiles and 44% of hebephiles reported being sexually victimized in their own childhoods. Pedophiles reported being molested at a younger age than hebephiles. Both groups appear to chose their age specific victims in accordance with the age of their own experience of sexual victimization. Although the cause of child molestation remains undetermined these results support social learning and modeling theories. PMID- 8455001 TI - A rapid dot-blot method for species identification of bloodstains. AB - A very simple and rapid test for species identification is reported. Extracts of bloodstains were applied to a synthetic porous membrane and dried. The membrane was then quenched with glycine buffered saline containing BSA and Tween 20. A suspension of colloidal gold particles (GP) coated with rabbit antiserum to human IgG was poured onto, gently whirled and aspirated through the membrane. Spots from the human and monkey bloodstains became red, whereas those from other species of animals remained unstained. This test was completed within 3 to 4 min, and the antibody-coated GP reagent was prepared within 20 min using a very small quantity of antiserum. Cellulose acetate membranes of 0.45 microns or more in pore size were appropriate to this test. PMID- 8455002 TI - The structural identification of a methyl analog of methaqualone via 2 dimensional NMR techniques. AB - A submission to the Drug Enforcement Administration North Central Laboratory of a substance believed to be a structural analog of methaqualone hydrochloride precipitated an interest in being able to obtain a rapid and positive identification of such compounds. Both mass spectrometry and proton NMR spectroscopy (1-dimensional) provided evidence to suggest that the structural analog possessed a second methyl group in the molecule, relative to methaqualone, and that the methyl group was attached to the existing methyl-substituted phenyl ring. By application of proton 2-dimensional (2-D) NMR techniques, specifically the homonuclear shift correlation spectroscopy (COSY) and 2-D NOE (NOESY), the precise location of the methyl group in this unknown methaqualone analog was established and shown to have the structure 2. PMID- 8455003 TI - Poisonings associated with cyanide in over the counter cold medication in Washington State, 1991. AB - In March 1991, four cyanide poisonings were identified in Washington State. Three of these, one nonfatal and two fatal, were directly linked to the consumption of capsules of Sudafed-12 hour cold relief capsules. This article presents the details of these cases including the chronology, causes of death, autopsy and toxicological findings. The fourth case, also fatal, occurred after extensive publicity surrounding the poisonings, and was determined to be a copy-cat case intended to mimic the consumption of tainted Sudafed. The investigation and distinguishing features of this case are also discussed. A further cyanide poisoning occurred in Canada shortly after these incidents and had similar features to the copy-cat case. PMID- 8455004 TI - Fatality due to recreational use of chlorodifluoromethane and chloropentafluoroethane. AB - Reports on fatalities of chlorofluorocarbons usually involve chlorotrifluoroethane, trichlorofluoromethane, dichlorodifluoromethane or chlorodifluoromethane, where analysis was done using packed column gas chromatography. In this case a death was caused by an azeotropic mixture of chlorodifluoromethane and chloropentafluoroethane, a combination that has not previously been reported in the forensic literature. This report details the analysis using mass selective detection employing capillary gas chromatography columns currently used in many toxicology laboratories. Postmortem toxicology revealed blood concentrations of chlorodifluoromethane and chloropentafluoroethane of 71 mg/L and 0.30 mg/L, respectively. Brain, liver, and lung concentrations of chlorodifluoromethane were (mg/kg) 2.8, 4.4, and 1.6, respectively. Brain, liver, and lung concentrations of chloropentafluoroethane were (mg/kg) 0.80, 0.80, and 0.11, respectively. The victim's blood contained 5.5 mg/L caffeine. Lidocaine, used in resuscitation attempts, was also present in the victim's blood. No other alkali-extractable drugs or volatile alcohols were detected in the victim's blood. The cause of death was acute respiratory arrest due to chlorofluorocarbon inhalation. PMID- 8455005 TI - The meaning of an accessory projectile. AB - A previously expended pistol casing was removed from a gunshot wound after an apparent accidental shooting. Examination of this foreign body indicated it had ridden the bore ahead of the bullet. Further investigation disclosed this as a deliberate but ignorant means to load an already loaded weapon. The assailants then fired at a passerby and killed him. Disclosure of the foreign body by X-ray, recovery and examination at autopsy were used to corroborate the circumstances and allowed charges of criminally negligent homicide to be placed. PMID- 8455006 TI - Cerebral intraventricular lipoma and sudden death. AB - A lipoma in the left lateral cerebral ventricle of a 73-year-old male is reported. This rather infrequently occurring lesion was an incidental finding in the patient's postmortem examination and probably accounted for the acute hydrocephalus that lead to his sudden death. PMID- 8455007 TI - What's that that "happens"? PMID- 8455008 TI - Use of erythropoietin in Jehovah's Witness children following acute gastrointestinal blood loss. AB - The decision to transfuse children in families practicing the Jehovah's Witness faith with human blood products raises medical, legal, and moral questions. Two cases are presented in which recombinant human erythropoietin was used in pediatric patients as an alternative following acute gastrointestinal hemorrhage. The patients demonstrated increased hematocrit levels obviating the need for blood transfusion. Although erythropoietin is not an alternative to hemotransfusion in the unstable patient, it may be an option in the hemodynamically uncompromised Jehovah's Witness patient following acute blood loss. PMID- 8455009 TI - Geriatric oncology. AB - The rapid increase in persons aged 65 and older will account for 20% of the total United States population by the year 2030. The incidence of malignancy likewise increases with advancing age. These factors are likely to result in an epidemic of geriatric cancer cases. Physicians should become knowledgeable on current issues in geriatric oncology which include: how to appropriately select geriatric patients with malignancies for surgical, medical or radiotherapeutic intervention; age as a bias for treatment selection; toxicities from cancer therapy in the elderly and how they can be modified; cancer screening and prevention measures in the elderly, and the special issues of informed consent and pain control in the geriatric cancer patient. PMID- 8455010 TI - Managed care and restraint of trade. PMID- 8455011 TI - A medical history timeline. PMID- 8455013 TI - Deposition deportment. PMID- 8455012 TI - Infectious disease, interleukin-1 and central nervous system. AB - Host mediators are responsible for inducing many of the nonspecific, common symptoms of illness. Several of these responses, including the induction of fever, increased levels of glucocorticoid, and increased sleep are mediated by the central nervous system (CNS). Interleukin-1 appears to be an important, but not the only, cytokine involved in activating these processes. Numerous unresolved questions remain regarding cytokine activation of the CNS, such as the neuroanatomical and neurochemical pathways involved in these responses; why these responses vary in magnitude and duration; what are the roles of individual cytokines in inducing these responses during infectious disease. PMID- 8455014 TI - The epidemic of family violence. How can we help? PMID- 8455015 TI - Governor Chiles' blueprint for health security. PMID- 8455016 TI - Generalist physicians. PMID- 8455017 TI - Actions of cholinergic drugs in the nematode Ascaris suum. Complex pharmacology of muscle and motorneurons. AB - The cholinergic agonists acetylcholine (ACh), nicotine, and pilocarpine produced depolarizations and contractions of muscle of the nematode Ascaris suum. Dose dependent depolarization and contraction by ACh were suppressed by about two orders of magnitude by 100 microM d-tubocurarine (dTC), a nicotinic antagonist, but only about fivefold by 100 microM N-methyl-scopolamine (NMS), a muscarinic antagonist. NMS itself depolarized both normal and synaptically isolated muscle cells. The muscle depolarizing action of pilocarpine was not consistently antagonized by either NMS or dTC. ACh receptors were detected on motorneuron classes DE1, DE2, DI, and VI as ACh-induced reductions in input resistance. These input resistance changes were reversed by washing in drug-free saline or by application of dTC. NMS applied alone lowered input resistance in DE1, but not in DE2, DI, or VI motorneurons. In contrast to the effect of ACh, the action of NMS in DE1 was not reversed by dTC, suggesting that NMS-sensitive sites may not respond to ACh. Excitatory synaptic responses in muscle evoked by depolarizing current injections into DE1 and DE2 motorneurons were antagonized by dTC; however, NMS antagonized the synaptic output of only the DE1 and DE3 classes of motorneurons, an effect that was more likely to have been produced by motorneuron conduction failure than by pharmacological blockade of receptor. The concentration of NMS required to produce these changes in muscle polarization and contraction, ACh antagonism, input resistance reduction, and synaptic antagonism was 100 microM, or more than five orders of magnitude higher than the binding affinity for [3H]NMS in larval Ascaris homogenates and adult Caenorhabditis elegans (Segerberg, M. A. 1989. Ph.D. thesis. University of Wisconsin-Madison, Madison, WI). These results describe a nicotinic-like pharmacology, but muscle and motorneurons also have unusual responses to muscarinic agents. PMID- 8455018 TI - Glucose tolerance factor reduces blood glucose and free fatty acids levels in diabetic rats. AB - Effect of Glucose Tolerance Factor (GTF) extracted from commercially available yeast extract powder was examined on streptozotocin diabetic rats. Different doses of GTF preparation were injected into diabetic rats, with no addition of exogenous insulin. Within two hours there was a significant decrease both in blood glucose and free fatty acids (FFA) levels in the diabetic animals, indicating an anti-diabetic potential of GTF. PMID- 8455019 TI - Synthesis and cytotoxicity of some cyclometallated palladium complexes. AB - Several monomeric cyclometallated palladium complexes have been prepared by bridge opening reactions of their corresponding dimeric precursors with various amines. The complexes were characterized by elemental analyses and proton NMR spectroscopy. The general formula for the complexes can be given as Pd(N-C)LX where (N-C) is an aromatic or aliphatic amine coordinated as a chelating ligand through the amine and a formal cyclometallated Pd-C bond; L = amine, X = chloride or acetate. A unique complex based on the cyclopalladation of 2-phenyl phenanthroline was also prepared directly. The series of complexes was screened for cytotoxicity against a panel of seven human tumor cell lines. All complexes were found to be cytotoxic (IC50) at micrograms/ml concentrations, while two complexes also displayed some differential cytotoxicity. PMID- 8455020 TI - Carbonic anhydrase inhibitors. Part 11. Coordination compounds of heterocyclic sulfonamides with lanthanides are potent inhibitors of isozymes I and II. AB - A number of 22 lanthanide-containing coordination compounds of sulfonamides 2 and 3 were prepared and characterized by elemental analysis and spectroscopic data. The new compounds proved to be highly potent inhibitors of isozymes I and II of carbonic anhydrase. PMID- 8455021 TI - High-affinity choline transport sites: use of [3H]hemicholinium-3 as a quantitative marker. AB - High-affinity choline transport (HAChT), the rate-limiting and regulatory step in acetylcholine (ACh) synthesis, is selectively localized to cholinergic neurons. Hemicholinium-3 (HC3), a potent and selective inhibitor of HAChT, has been used as a specific radioligand to quantify HAChT sites in membrane binding and autoradiographic studies. Because both HAChT velocity and [3H]HC3 binding change as in vivo activity of cholinergic neurons is altered, these markers are also useful measures of cholinergic neuronal activity. Evidence that [3H]HC3 is a specific ligand for HAChT sites on cholinergic terminals is reviewed. The ion requirements of HAChT and [3H]HC3 binding indicate that sodium and chloride are required for recognition of both choline and [3H]HC3. A common recognition site is also indicated by the close correspondence of the potency of HC3 and choline analogues for inhibiting both HAChT and [3H]HC3 binding. The parallel regional distributions of both markers in adult brain, during development and after specific lesions, all indicate specific cholinergic localization. The close association of HAChT and [3H]HC3 binding sites is also supported by parallel regulatory changes occurring after in vivo drug treatments and in vitro depolarization. Overall, the data indicate a close association between HAChT and [3H]HC3 binding and are consistent with the sites being identical. Methodologic considerations in using [3H]HC3 as a ligand and considerations in interpretation of results are also discussed. PMID- 8455022 TI - Excitatory amino acid-mediated cytotoxicity and calcium homeostasis in cultured neurons. AB - A large body of evidence suggests that disturbances of Ca2+ homeostasis may be a causative factor in the neurotoxicity induced by excitatory amino acids (EAAs). The route or routes by which an increase in intracellular calcium concentration ([Ca2+]i) is mediated in vivo are presently not clarified. This may partly reflect the complexity of intact nervous tissue in combination with the relative unspecific action of the available "calcium antagonists," e.g., blockers of voltage-sensitive calcium channels. By using primary cultures of cortical neurons as a model system, it has been found that all EAAs stimulate increases in [Ca2+]i but via different mechanisms. By using the drug dantrolene, it has been shown that 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propionate (AMPA) apparently exclusively stimulates Ca2+ influx through agonist-operated calcium channels and voltage-operated calcium channels. Increased [Ca2+]i due to exposure to kainate (KA) is for the major part caused by influx, as in the case of AMPA, but a small part of the increase in [Ca2+]i may be attributed to a release of Ca2+ from intracellular stores. Quisqualate (QA) stimulates Ca2+ release from an intracellular store that is independent of Ca2+ influx; presumably this store is activated by inositol phosphates. The increase in [Ca2+]i due to exposure to glutamate or N-methyl-D-aspartate (NMDA) may be compartmentalized into three components, one of which is related to influx and the other two to Ca2+ release from internal stores. Only one of the latter stores is dependent on Ca2+ influx with regard to release of Ca2+, whereas the other is activated by some other second messengers or, alternatively, directly coupled to the receptor. In muscles dantrolene is known to inhibit Ca2+ release from the sarcoplasmic reticulum, and also in neurons dantrolene inhibits an equivalent release from one or more hitherto unidentified internal Ca2+ pool(s). By using this drug it has been possible to show to what extent these Ca2+ stores are involved in the toxicity observed subsequent to exposure to the EAAs. It turned out that dantrolene, even under conditions allowing Ca2+ influx, inhibited toxicity induced by QA, NMDA, and glutamate, whereas that induced by AMPA or KA was unaffected. In combination with the findings that dantrolene inhibited release from the intracellular stores activated by QA, NMDA, and glutamate, it may be concluded that Ca2+ influx per se is not the primary event causing toxicity following exposure to these EAAs in these neurons. However, it may certainly be involved in the cases of toxicity induced by AMPA and KA.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8455023 TI - Modulation of the serine base exchange enzyme activity of rat brain membranes by amphiphilic cations and amphiphilic anions. AB - The biosynthesis of phosphatidylserine in mammalian tissues is catalyzed by the serine base exchange enzyme. The activity of this membrane-bound enzyme can be manipulated by amphiphiles. Amphiphilic cations, such as oleylamine, W-7, chlorpromazine, and didodecyldimethylamine, stimulate the serine base exchange activity. Amphiphilic anions, such as bis(2-ethylhexyl) hydrogen phosphate and cholesterol sulfate, inhibit the serine base exchange activity. These effects are more pronounced at pH 7.0 than at the pH optimum of 8.5 for this enzyme. Both the stimulators and the inhibitors alter the Vmax values without changing the Km value for serine, suggesting that their mechanism of action is related to interactions of the membrane-bound cosubstrate, phosphatidylethanolamine, with the membrane-bound enzyme. The optimal concentration of stimulator varies with the amount of membrane protein present; however, supraoptimal concentrations cause inhibitions. It is proposed that the amphiphilic cations enhance the interaction of the phosphorylethanolamine moiety of the membrane-bound cosubstrate with the enzyme and the amphiphilic anions interfere with such an interaction. Some of the pharmacological properties of these amphiphilic cations, employed clinically as antidepressants, may be mediated by modulation of the serine base exchange enzyme activity. PMID- 8455024 TI - Fast and local electrochemical monitoring of noradrenaline release from sympathetic terminals in isolated rat tail artery. AB - Noradrenaline release from sympathetic nerve terminals was evoked by electrical nerve stimulation of an isolated segment of rat tail artery. This release was recorded by a carbon fiber electrode combined with differential pulse amperometry. The active part of the electrode (one carbon fiber 8 microns in diameter and 50 microns in length) was placed in close contact with the arterial surface. The oxidation current appearing at +120 mV and corresponding to the local noradrenaline concentration at the electrode surface was recorded every 0.5 s. No oxidation current was detected under resting conditions, but electrical stimulation evoked an immediate increase in this current. This response was suppressed when tetrodotoxin was added to the perfusion medium and was enhanced when noradrenaline reuptake was inhibited by cocaine. The amplitude of the response was increased with increasing stimulation frequencies (2-25 Hz) and train lengths (1-16 pulses). Finally, the time resolution of the method (0.5 s) was good enough to show that noradrenaline release precedes the postsynaptic response, i.e., the electrically evoked contraction of the artery. PMID- 8455025 TI - Physiological stimulation increases nonoxidative glucose metabolism in the brain of the freely moving rat. AB - The effects of mild stress on nonoxidative glucose metabolism were studied in the brain of the freely moving rat. Extracellular lactate levels in the hippocampus and striatum were monitored at 2.5-min intervals with microdialysis coupled with an enzyme-based flow injection analysis system. Ten minutes of restraint stress led to a 235% increase in extracellular lactate levels in the striatum. A 5-min tail pinch caused an increase of 193% in the striatum and 170% in the hippocampus. Local application of tetrodotoxin in the striatum blocked the rise in lactate following tail pinch and inhibited the subsequent clearance of lactate from the extracellular fluid. Local application of the noncompetitive N-methyl-D aspartate receptor antagonist MK-801 had no effect on the tail pinch-stimulated increase in lactate in the striatum. These results show that mild physiological stimulation can lead to a rapid increase in nonoxidative glucose metabolism in the brain. PMID- 8455026 TI - Studies on the role of B-50 (GAP-43) in the mechanism of Ca(2+)-induced noradrenaline release: lack of involvement of protein kinase C after the Ca2+ trigger. AB - The involvement of B-50, protein kinase C (PKC), and PKC-mediated B-50 phosphorylation in the mechanism of Ca(2+)-induced noradrenaline (NA) release was studied in highly purified rat cerebrocortical synaptosomes permeated with streptolysin-O. Under optimal permeation conditions, 12% of the total NA content (8.9 pmol of NA/mg of synaptosomal protein) was released in a largely (> 60%) ATP dependent manner as a result of an elevation of the free Ca2+ concentration from 10(-8) to 10(-5) M Ca2+. The Ca2+ sensitivity in the micromolar range is identical for [3H]NA and endogenous NA release, indicating that Ca(2+)-induced [3H]NA release originates from vesicular pools in noradrenergic synaptosomes. Ca(2+)-induced NA release was inhibited by either N- or C-terminal-directed anti B-50 antibodies, confirming a role of B-50 in the process of exocytosis. In addition, both anti-B-50 antibodies inhibited PKC-mediated B-50 phosphorylation with a similar difference in inhibitory potency as observed for NA release. However, in a number of experiments, evidence was obtained challenging a direct role of PKC and PKC-mediated B-50 phosphorylation in Ca(2+)-induced NA release. PKC pseudosubstrate PKC19-36, which inhibited B-50 phosphorylation (IC50 value, 10(-5) M), failed to inhibit Ca(2+)-induced NA release, even when added before the Ca2+ trigger. Similar results were obtained with PKC inhibitor H-7, whereas polymyxin B inhibited B-50 phosphorylation as well as Ca(2+)-induced NA release. Concerning the Ca2+ sensitivity, we demonstrate that PKC-mediated B-50 phosphorylation is initiated at a slightly higher Ca2+ concentration than NA release. Moreover, phorbol ester-induced PKC down-regulation was not paralleled by a decrease in Ca(2+)-induced NA release from streptolysin-O-permeated synaptosomes. Finally, the Ca(2+)- and phorbol ester-induced NA release was found to be additive, suggesting that they stimulate release through different mechanisms. In summary, we show that B-50 is involved in Ca(2+)-induced NA release from streptolysin-O-permeated synaptosomes. Evidence is presented challenging a role of PKC-mediated B-50 phosphorylation in the mechanism of NA exocytosis after Ca2+ influx. An involvement of PKC or PKC-mediated B-50 phosphorylation before the Ca2+ trigger is not ruled out. We suggest that the degree of B-50 phosphorylation, rather than its phosphorylation after PKC activation itself, is important in the molecular cascade after the Ca2+ influx resulting in exocytosis of NA. PMID- 8455027 TI - Lithium enhances muscarinic receptor-stimulated CDP-diacylglycerol formation in inositol-depleted SK-N-SH neuroblastoma cells. AB - The psychotherapeutic action of Li+ in brain has been proposed to result from the depletion of cellular inositol secondary to its block of inositol monophosphatase. This action is thought to slow phosphoinositide resynthesis, thereby attenuating stimulated phosphoinositidase-mediated signal transduction in affected cells. In the present study, the effect of Li+ on muscarinic receptor stimulated formation of the immediate precursor of phosphatidylinositol, CDP diacylglycerol (CDP-DAG), has been examined in human SK-N-SH neuroblastoma cells that have been cultured under conditions that alter the cellular content of myo inositol. Resting neuroblastoma cells, like brain cells in vivo, were found to concentrate inositol from the culture medium, achieving an intracellular level of 60.0 +/- 4 nmol/mg of protein. The addition of carbachol to [3H]cytidine prelabeled cells elicited a four- to fivefold increase in the accumulation of labeled CDP-DAG. This stimulated formation of [3H]CDP-DAG was completely blocked by the addition of 10 microM atropine, was not dependent on the presence of Li+, nor was it affected by co-incubation with myo-inositol. This result was in sharp contrast to findings in rat brain slices, in which carbachol-stimulated formation of [3H]CDP-DAG was potentiated approximately 10-fold by Li+ and substantially reduced by coincubation with inositol. The formation of [3H]CDP-DAG in labeled SK N-SH cells by carbachol was both concentration and time dependent. The order of efficacy of muscarinic ligands in stimulating [3H]-CDP-DAG accumulation paralleled that established in these cells for inositol phosphate accumulation, i.e., carbachol > or = oxotremorine-M > bethanecol > or = arecoline > oxotremorine > pilocarpine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455028 TI - Deletions of the synenkephalin domain which do not alter cell-specific proteolytic processing or secretory targeting of human proenkephalin. AB - To identify signals that direct the proteolytic processing and regulated secretion of human proenkephalin (hPE), we have transfected the hPE gene or minigene constructs into pituitary tumor cells, either rat GH4Cl cells or mouse AtT-20 cells. Cells transfected with either the hPE gene or minigene contained similar levels of methionine-enkephalin (ME)-containing peptides and hPE mRNA. In the GH4Cl clones, ME was present predominantly in high-molecular-mass forms (5-25 kDa). In contrast, the AtT-20 clones contained almost exclusively free ME and low molecular-mass forms (< 5 kDa), with very little high-molecular-mass species present. Thus, among pituitary cells, corticotroph-derived cells appear better equipped to process hPE than lactotroph-derived cells. Despite limited proteolytic processing, GH4Cl clones secreted large amounts of unprocessed (> 20 kDa) hPE into the medium, making up to 10% of endogenous rat prolactin secretion. Both precursor and processed forms of ME were cosecreted acutely (< 1 h) with rat prolactin, and release of both polypeptides was stimulated up to 12-fold by secretagogues. Thus, complete proteolytic processing was not required for accurate targeting of hPE to the regulated secretory pathway. When transfected with constructs bearing deletions of amino-terminal amino acids 2-43 or 2-67, i.e., part or nearly all of the synenkephalin moiety, GH4Cl cells handled the modified protein much like cells expressing the complete protein. They did not process the modified hPE extensively, but the protein was correctly targeted to the regulated secretory pathway. AtT-20 cells transfected with truncated hPE cDNA constructs expressed and processed the protein as efficiently as cells expressing unmodified hPE and expressed predominantly low-molecular-mass forms of ME. Therefore, the structural features required for correct targeting and processing are not present in the cysteine-rich amino-terminal third of the prohormone. It is interesting that the deletions did not include the SHLL peptide motif in synenkephalin, a motif that has been proposed as a sorting signal. PMID- 8455029 TI - Differential glycosylation of the 5A11/HT7 antigen by neural retina and epithelial tissues in the chicken. AB - The 5A11/HT7 antigen, a member of the immunoglobulin supergene family, has been implicated in heterotypic cell-cell interactions during retina development. Immunopurified 5A11 antigen isolated from Nonidet P-40-solubilized retina membranes had two components as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), a 45.5-kDa doublet and a 69-kDa polypeptide. Immunoreactive bands of 46-50 kDa were recognized following SDS-PAGE of detergent-solubilized membrane proteins from liver, kidney, and erythrocytes. Treatment with N-glycosidase F (EC 3.2.2.18) converted the 45.5-50-kDa immunoreactive polypeptides from all tissues to 32 kDa, indicating that the observed differences in molecular mass were due to differences in glycosylation. N-Glycosidase F treatment also converted the 69-kDa form from retina to 46 kDa, indicating a different polypeptide core than the 32-kDa species. Treatment with endo-beta-N-acetylglucosaminidase H (EC 3.2.1.96) resulted in modest increases in electrophoretic mobility due to hydrolysis of high mannose or hybrid oligosaccharides and lack of hydrolysis of complex oligosaccharides resistant to endo-beta-N-acetylglucosaminidase H digestion. Immunoreactivity was retained after deglycosylation. Much of the difference in molecular weight could be attributed to variations in sialylation. The higher molecular mass species of the 45.5-kDa doublet from retina and the polypeptides from other tissues were susceptible to neuraminidase (EC 3.2.1.18) and O-glycosidase (endo-alpha-N acetylgalactosaminidase; EC 3.2.1.97) digestion. Labeling with elderberry bark lectin (specific for alpha 2,6-linked sialic acid) was confined to the higher molecular mass species of the 45.5-kDa doublet and was considerably greater in antigen derived from epithelia rather than neural retina. In paraffin sections of chick retina, elderberry bark lectin staining was confined to the retinal pigmented epithelium, photoreceptor cells, and bipolar cells with no staining of the Muller cells, which bear the bulk of the 5A11 antigen. These results indicate tissue-specific posttranslational modifications, particularly differences in sialylation of antigen-bearing polypeptides. PMID- 8455031 TI - Triiodothyronine is a high-affinity inhibitor of amino acid transport system L1 in cultured astrocytes. AB - The relationship between the transport of thyroid hormones and that of amino acids was examined by measuring the uptake of amino acids that are characteristic substrates of systems L, A, and N, and the effect of 3,3',5-triiodo-L-thyronine (T3) on this uptake, in cultured astrocytes. Tryptophan and leucine uptakes were rapid, Na(+)-independent, and efficiently inhibited by T3 (half-inhibition at approximately 2 microM). Two Na(+)-independent L-like systems (L1 and L2), common to leucine and aromatic amino acids, were characterized kinetically. System L2 had a low affinity for leucine and tryptophan (Km = 0.3-0.9 mM). The high affinity system L1 (Km approximately 10 microM for both amino acids) was competitively inhibited by T3 with a Ki of 2-3 microM (close to the T3 transport Km). Several T3 analogues inhibited system L1 and the T3 transport system similarly. Glutamine uptake and alpha-(methylamino)isobutyric acid uptake were, respectively, two and 200 times lower than tryptophan and leucine uptakes. T3 had little effect on the uptakes of glutamine and alpha -(methylamino)isobutyric acid. The results indicate that the T3 transport system and system L1 are related. PMID- 8455030 TI - Effect of inhibitors of eicosanoid metabolism on release of [3H]noradrenaline from the human neuroblastoma, SH-SY5Y. AB - Nordihydroguaiaretic acid (NDGA; a lipoxygenase inhibitor), LY-270766 (an inhibitor of 5-lipoxygenase), and the diacylglycerol lipase inhibitor RG 80267 completely eliminated potassium-evoked release of [3H]-noradrenaline ([3H]NA) from the human neuroblastoma clone SH-SY5Y with IC50 values of 10, 15, and 30 microM, respectively. In contrast, these inhibitors only partially inhibited carbachol-evoked release and had little effect on the calcium ionophore A23187 evoked release of NA in this cell line. Arachidonic acid partially inhibited potassium- and A23187-evoked release but did not reverse the inhibition of potassium-evoked release observed in the presence of RG 80267. These studies suggest that arachidonic acid (or its lipoxygenase products) are not important intermediates in the regulation of exocytosis in SH-SY5Y. This conclusion is strengthened by our studies in which SH-SY5Y cells were grown in medium supplemented with bovine serum albumin-linoleic acid (50 microM). Under these conditions there was a selective increase in content of membrane polyunsaturated fatty acids of the omega 6 series, including arachidonic acid; however, these changes did not effect potassium-, veratridine-, carbachol-, or calcium ionophore evoked release of [3H]NA. PMID- 8455032 TI - Dissociation of phosphorylation and translocation of a myristoylated protein kinase C substrate (MARCKS protein) in C6 glioma and N1E-115 neuroblastoma cells. AB - An 80-kDa protein labeled with [3H]myristic acid in C6 glioma and N1E-115 neuroblastoma cells has been identified as the myristoylated alanine-rich C kinase substrate (MARCKS protein) on the basis of its calmodulin-binding, acidic nature, heat stability, and immunochemical properties. When C6 cells preincubated with [3H]myristate were treated with 200 nM 4 beta-12-O-tetradecanoylphorbol 13 acetate (beta-TPA), labeled MARCKS was rapidly increased in the soluble digitonin fraction (maximal, fivefold at 10 min) with a concomitant decrease in the Triton X-100-soluble membrane fraction. However, phosphorylation of this protein was increased in the presence of beta-TPA to a similar extent in both fractions (maximal, fourfold at 30 min). In contrast, beta-TPA-stimulated phosphorylation of MARCKS in N1E-115 cells was confined to the membrane fraction only and no change in the distribution of the myristoylated protein was noted relative to alpha-TPA controls. These results indicate that although phosphorylation of MARCKS by protein kinase C occurs in both cell lines, it is not directly associated with translocation from membrane to cytosol, which occurs in C6 cells only. The cell-specific translocation of MARCKS appears to correlate with previously demonstrated differential effects of phorbol esters on stimulation of phosphatidylcholine turnover in these two cell lines. PMID- 8455033 TI - Cocaine and cocaethylene: microdialysis comparison of brain drug levels and effects on dopamine and serotonin. AB - Cocaethylene is a pharmacologically active metabolite resulting from concurrent cocaine and ethanol consumption. The effects of cocaine and cocaethylene on extracellular levels of dopamine in the nucleus accumbens, and serotonin in the striatum were characterized in vivo in the anesthetized rat. Both intravenous (3 mumol/kg) and intraperitoneal (44 mumol/kg) routes of administration were used. In addition to monitoring neurotransmitter levels, microdialysate levels of cocaine and cocaethylene were determined at 4-min intervals after intravenous administration, and at 20-min intervals after intraperitoneal administration. Extracellular levels of dopamine in the nucleus accumbens were increased to approximately 400% of preinjection value by both cocaine and cocaethylene when administered intravenously. Cocaine caused a significant increase of striatal serotonin to 200% preinjection value, whereas cocaethylene had no effect. Brain levels of cocaine and cocaethylene after intravenous administration did not differ. After intraperitoneal administration, extracellular levels of dopamine in the nucleus accumbens were increased to 400% of preinjection levels by cocaine, but were only increased to 200% of preinjection levels by cocaethylene, the difference being statistically significant. Serotonin levels were increased to 360% of preinjection levels by cocaine, but only to 175% of preinjection value by cocaethylene. Levels of cocaine attained in brain were significantly higher than those for cocaethylene, suggesting pharmacokinetic differences with the intraperitoneal route. These results confirm in vivo that cocaethylene is more selective in its actions than cocaine with respect to dopamine and serotonin uptake. In addition, route-dependent differences in attainment of brain drug levels have been observed that may impact on interpretations of the relative potency of the reinforcement value of these compounds. PMID- 8455034 TI - Purification of cytosolic malic enzyme from bovine brain, generation of monoclonal antibodies, and immunocytochemical localization of the enzyme in glial cells of neural primary cultures. AB - Cytosolic malic enzyme (EC 1.1.1.40) was purified from bovine brain 5,600-fold to a specific activity of 47 U/mg. The enzyme is a homotetramer with a subunit molecular mass of 60 kDa and an isoelectric point of 6.2. Mouse monoclonal antibodies raised against this enzyme were purified and shown to be monospecific, as indicated by immunoblotting. Immunocytochemical examination of rat astroglia rich primary cultures at the light microscopic level revealed colocalization of cytosolic malic enzyme with the astroglial marker glial fibrillary acidic protein. Also, a colocalization with the oligodendroglial marker myelin basic protein was found. Neurons in rat neuron-rich primary cultures did not show positive staining. The data suggest that cytosolic malic enzyme is a glial enzyme and is lacking in neurons. PMID- 8455035 TI - Protein methylation in cerebellar synaptosomes. AB - Synaptosomes from five regions of adult rat brain were isolated, analyzed for methyl acceptor proteins, and probed for methyltransferases by photoaffinity labeling. Methylated proteins of 17 and 35 kDa were observed in all regions, but cerebellar synaptosomes were enriched in a 21-26-kDa family of methyl acceptor proteins and contained a unique major methylated protein of 52 kDa and a protein of 50 kDa, which was methylated only in the presence of EGTA. When cerebellar and liver subcellular fractions were compared, the cytosolic fractions of each tissue contained methylated proteins of 17 and 35 kDa; liver membrane fractions contained few methylated proteins, whereas cerebellar microsomes had robust methylation of the 21-26-kDa group. Differential centrifugation of lysed cerebellar synaptosomes localized the 17- and 35-kDa methyl acceptor proteins to the synaptoplasm, the 21-26-kDa family to the synaptic membranes, and the 52-kDa to synaptic vesicles. The 21-26-kDa family was identified as GTP-binding proteins by [alpha-32P]GTP overlay assay; these proteins contained a putative methylated carboxyl cysteine, based on the presence of volatile methyl esters and the inhibition of methylation by acetylfarnesylcysteine. The 52-kDa methylated protein also contained volatile methyl esters, but did not bind [alpha-32P]GTP. When synaptosomes were screened for putative methyltransferases by S-adenosyl-L [methyl-3H]methionine photoaffinity labeling, a protein of 24 kDa was detected only in cerebellum, and this labeled protein was localized to synaptic membranes. PMID- 8455036 TI - Inhibition by 2-deoxyglucose and 1,5-gluconolactone of glycogen mobilization in astroglia-rich primary cultures. AB - The presence of glycogen in astroglia-rich primary cultures derived from the brains of newborn rats depends on the availability of glucose in the culture medium. On glucose deprivation, glycogen vanishes from the astroglial cultures. This decrease of glycogen content is completely prevented if 2-deoxyglucose in a concentration of > 1 mM or 1,5-gluconolactone (20 mM) is present in the culture medium. 2-Deoxyglucose itself or 3-O-methylglucose, a glucose derivative that is not phosphorylated by hexokinase, does not reduce the activity of glycogen phosphorylase purified from bovine brain or in the homogenate of astroglia-rich rat primary cultures. In contrast, deoxyglucose-6-phosphate strongly inhibits the glycogen phosphorylase activities of the preparations. Half-maximal effects were obtained at deoxyglucose-6-phosphate concentrations of 0.75 (phosphorylase a, astroglial culture), 5 (phosphorylase b, astroglial culture), 2 (phosphorylase a, bovine brain), or 9 mM (phosphorylase b, bovine brain). Thus, the block of glycogen degradation in these cells appears to be due to inhibition of glycogen phosphorylase by deoxyglucose-6-phosphate rather than deoxyglucose itself. These results suggest that glucose-6-phosphate, rather than glucose, acts as a physiological negative feedback regulator of the brain isoenzyme of phosphorylase and thus of glycogen degradation in astrocytes. PMID- 8455037 TI - Glutathione depletion induces heme oxygenase-1 (HSP32) mRNA and protein in rat brain. AB - In mammalian systems, the heme oxygenase (HO) isozymes HO-1 (HSP32) and HO-2 oxidatively cleave the heme molecule to produce bile pigments and carbon monoxide. Although HO-1 is inducible by various chemicals in systemic organs and cell culture systems, this communication reports for the first time the induction of this stress protein and its transcript by a chemical in the brain. In addition, this study demonstrates expression of HO-1 in select populations of cells in the brain in response to GSH depletion. Specifically, treatment of adult rats with diethyl maleate (DEM; 4.7 mmol/kg) caused a pronounced decrease in brain GSH content within 1 h. GSH levels remained significantly depressed for at least 24 h postinjection. Northern blot analysis of brain poly(A)+ mRNA following DEM treatment revealed on the average a sixfold increase in the 1.8-kb HO-1 mRNA level compared with that of controls; concomitant with this change was a decrease in GSH levels. Total brain HO activity was not significantly altered along with the increase in HO-1 mRNA level. The increase in transcription of HO-1 was a direct response to GSH depletion, as judged by the observation that treatment of neonatal rats with L-buthionine-(S,R)-sulfoximine (BSO) (3 mmol/kg, twice daily, for 2 days), a selective inhibitor of GSH synthesis, caused a marked depression in total brain GSH level and a concomitant increase in brain 1.8-kb HO-1 mRNA content. The magnitude of the increase was up to approximately 11.5-fold that of the control level, as evidenced by northern blot analysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455038 TI - Transcription-independent activation of ornithine decarboxylase activity by heparin in cloned cerebral endothelial cells. AB - Heparin, a highly sulfated glycosaminoglycan, is known to be obligatory for long term endothelial cell cultures; it potentiates the mitogenic activities of endothelial cell growth factors and prolongs the replicative life span of the cells. Here we have shown that besides its growth factor-supportive role, heparin exerts a specific action on cerebral capillary endothelial cells (cECs), unrelated to serum or growth factors, by increasing activity of ornithine decarboxylase (ODC; EC 4.1.1.17) in these cells. For our experiments we have used two different types of cloned cECs: type I cECs, grown in the presence of endothelial cell growth factor and heparin, and type II cECs, usually cultivated without growth factors. Heparin action on ODC activity was shown to be dose dependent within the range of 1-100 micrograms/ml. Increasing concentrations of or depletion of endothelial cell growth factor from type I cultures had no effect on ODC activity. The increase in enzyme activity was highest after 30 min to 1 h of heparin treatment. As evidenced by northern analysis, the heparin-mediated enhancement of ODC activity was not accompanied by changes of ODC mRNA levels. Studies of DNA replication revealed that in the absence of heparin-binding growth factors, heparin did not affect the proliferative activity of cloned cECs. PMID- 8455039 TI - Role of histidine residues in agonist and antagonist binding sites of A1 adenosine receptor. AB - The influence of pH on the equilibrium dissociation constant and on kinetic association and dissociation constants was studied for adenosine receptor agonist L-N6-[adenine-2,8-3H, ethyl-2-3H]phenylisopropyladenosine ([3H]R-PIA) and antagonist 8-cyclopentyl-1,3-[3H]-dipropylxanthine ([3H]DPCPX). Two ionizable groups, of pK 7.0 and pK 7.4, are involved in the [3H]R-PIA associations with high- and low-affinity states of the receptor, and another group, of pK 6.0, is involved in the association with the low-affinity state. No ionizable group is involved in the dissociation process for the high-affinity state, whereas two ionizable groups, of pK 6.0 and 6.5, are involved in the low-affinity state. For [3H]DPCPX, three ionizable groups (pK 6.0, 7.4, and 8.0) are involved in the association process and only one group, (pK 6.0), is involved in the dissociation step. The apparent pK values obtained agree with histidine residues. We thus studied the effect of diethylpyrocarbonate (DEP), which reacts irreversibly with histidine residues, on agonist and antagonist binding to A1 adenosine receptors from pig brain cortical membranes. DEP treatment of membrane reduced the affinity (KD) and the total binding (R) of the agonist and the antagonist. Membrane preincubation with unlabeled ligand (R-PIA or DPCPX) prevented the effect of DEP modification observed when the same ligand, but with label, is added to the same membranes, but did not prevent the DEP modification on different, labeled ligand.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455040 TI - Direct cytotoxicity of ethylcholine mustard aziridinium in cerebral microvascular endothelial cells. AB - The choline analogue ethylcholine mustard aziridinium (AF64A) is a potent and irreversible inhibitor of choline uptake in brain synaptosomes and is used as a neurotoxin to produce animal models of cholinergic hypofunction. However, previous studies have shown that intraocular administration of AF64A in rats not only reduced the number of cholinergic neurons in the retina, but also induced ultrastructural alterations in the microvasculature. The purpose of this study was to investigate whether AF64A has a direct cytotoxic effect on endothelial cells. As revealed by the measurement of lactate dehydrogenase activity in the culture medium, AF64A produced similar concentration-dependent cellular damage in cultures of bovine cerebral endothelial cells and in the human cholinergic neuroblastoma cell line SK-N-MC, but not in bovine cerebral smooth muscle cells. The toxic effect of AF64A correlated well with the affinity of the choline transport system detected in each cell type. The effect of the toxin on endothelial cells was mediated by its interaction with the endothelial cell choline carrier, as demonstrated by the following observations: (a) AF64A inhibited [3H]choline uptake in a concentration-dependent manner in both cultured and freshly isolated cerebral endothelial cells, and (b) the addition of choline or hemicholinium-3 to the culture medium prevented the AF64A-induced toxicity in endothelial cell cultures. PMID- 8455041 TI - The effect of the B subunit of cholera toxin on the action of nerve growth factor on PC12 cells. AB - Exogenous gangliosides, especially ganglioside GM1 (GM1), seem to potentiate the action of nerve growth factor (NGF). We have examined the possible regulation of the NGF signaling pathway in PC12 cells by the B subunit of cholera toxin (CTB), which binds to endogenous GM1 specifically and with a high affinity. CTB treatment (1 micrograms/ml) enhanced NGF-induced neurite outgrowth from PC12 cells, NGF-induced activation of ribosomal protein S6 kinase, and NGF-induced stimulation of trk phosphorylation. CTB plus NGF also caused a greater inhibition of [3H]thymidine incorporation into DNA than did NGF alone. These enhancing effects of CTB were blocked by the presence of cytochalasin B in the culture medium but were not affected by the presence of colchicine or by the depletion of Ca2+ in the medium. 125I-NGF binding experiments revealed that CTB treatment did not affect the specific binding of NGF to the cells. These results strongly suggest that the binding of cell surface GM1 by CTB modulates the pathway of intracellular signaling initiated by NGF and that the association of CTB with a cytoskeletal component is essential for these effects. PMID- 8455042 TI - Cholesterol synthesis in regenerating peripheral nerve is not influenced by serum cholesterol levels. AB - Following a nerve crush, cholesterol from degenerating myelin is retained within the nerve and reutilized for new myelin synthesis during nerve regeneration, apparently via a lipoprotein-mediated process. Because at least some serum components have access to the endoneurium of injured nerve, it has been suggested that serum lipoproteins are also significant contributors of cholesterol to Schwann cells during nerve regeneration. To test this hypothesis, serum cholesterol levels were reduced by > 90% with 4-aminopyrazolopyrimidine, followed by measurement of the activity of the key regulatory enzyme in cholesterol synthesis, 3-hydroxy-3-methylglutaryl-CoA reductase. Treatment with 4 aminopyrazolopyrimidine caused a sevenfold increase in 3-hydroxy-3-methylglutaryl CoA reductase activity in kidney but had no effect on the activity of this enzyme in either intact or regenerating sciatic nerve. These data indicate that serum derived cholesterol is neither necessary for nor contributes significantly to myelin synthesis in regenerating nerve. PMID- 8455043 TI - Chronic ethanol exposure potentiates NMDA excitotoxicity in cerebral cortical neurons. AB - The effect of acute and chronic ethanol exposure on excitotoxicity in cultured rat cerebral cortical neurons was examined. Neuronal death was quantitated by measuring the accumulation of lactate dehydrogenase (LDH) in the culture media 20 h after exposure to NMDA. Addition of NMDA (25-100 microM) to the culture dishes for 25 min in Mg(2+)-free buffer resulted in a dose-dependent increase in LDH accumulation. Phase-contrast microscopy revealed obvious signs of cellular injury as evidenced by granulation and disintegration of cell bodies and neuritic processes. Chronic exposure of neuronal cultures to ethanol (100 mM) for 96 h followed by its removal before NMDA exposure, significantly increased NMDA stimulated LDH release by 36 and 22% in response to 25 microM and 50 microM NMDA, respectively. Neither basal LDH release nor that in response to maximal NMDA (100 microM) stimulation was altered by chronic alcohol exposure. In contrast to the effects of chronic ethanol on NMDA neurotoxicity, inclusion of ethanol (100 mM) only during the NMDA exposure period significantly reduced LDH release by approximately 50% in both control and chronically treated dishes. This reduction by acute ethanol was also observed under phase-contrast microscopy as a lack of development of granulation and a sparing of disintegration of neuritic processes. These results indicate that chronic exposure of ethanol to cerebral cortical neurons in culture can sensitize neurons to excitotoxic NMDA receptor activation. PMID- 8455044 TI - Selective and nonselective protective effects of brain-derived neurotrophic factor for dopaminergic neurons in vitro. PMID- 8455045 TI - Selection to postmenopausal therapy by women's characteristics. AB - Many surveys have shown that women using postmenopausal hormone therapy have a lower incidence of cardiovascular diseases and lower overall mortality. The purpose of this study was to compare past and non-users with current users of hormone therapy in regard to characteristics known to, or assumed to, predict poor subsequent health (indicators). The main data source was a survey in 1989 of a random sample (n = 2000, 86% response rate) of 45-64 year-old Finnish women. Among women with their uterus, after adjusting for age and urbanism, of the 21 indicators studied, 10 suggested a poorer and none a better health prognosis for the non-users than for current users. Many differences were greater among older women, suggesting a cohort effect or long-term users being an especially selected group. Among hysterectomized women, differences between users and non-users were similar or smaller than among women with uteri. The past users were more similar to non-users than current users. Our study suggests that women with a better health prognosis are selected or select themselves for hormone therapy, and that may impede interpretation of observational studies on hormone therapy and health. PMID- 8455046 TI - A randomized trial of a decisional aid for mental capacity assessments. AB - The objective of this study was to evaluate the clinical utility of a decisional aid for mental capacity assessments which was developed using a group judgment methodology. This was carried out by a randomized, controlled trial. The subjects comprised 64 University of Toronto psychiatry residents in postgraduate years 1 through 4. Residents were randomized to carry out mental capacity assessments on simulated cases with, or without, the use of the decisional aid. The main outcome measure was the extent of agreement between the mental capacity determinations of residents and those of experts. There was no difference between the intervention and control groups with respect to the overall mean level of agreement with experts (0.87 vs 0.86, p = 0.88; 95% confidence interval for the difference between the study groups, -0.07 to +0.08). A logistic regression analysis, which adjusted for imbalances between the groups, also revealed no difference between the groups in their agreement with experts. The mean time per competency assessment was significantly longer in the intervention group (19.1 vs 10.8 min; p < 0.001). It was concluded that the decisional aid did not improve the ability of the psychiatry residents to make mental capacity assessments on simulated cases. Despite relatively limited formal training, the psychiatry residents had a high level of agreement with experts. PMID- 8455047 TI - Graphical display of categorical data. AB - Categorical data are usually displayed in medical publications with pie graphs and bar graphs. We here consider some of the problems that occur in displaying the rank, magnitude, width, and spacing of categorical data. A solution to some of these problems is offered by the dot chart, which has been used in other scientific literature, but not in medical publications. The dot chart can be a preferred alternative to pie graphs and offers a useful alternative to bar graphs. Dot charts can also be helpful in displaying categorical data for two groups. PMID- 8455048 TI - Design and analysis of drug safety studies, with special reference to sporadic drug use and acute adverse reactions. AB - A methodological approach for analysis of drug safety data which permits the calculation of risk measures for intermittent exposures and acute adverse reactions is presented. This method allows for the observation of exposures that are temporary and which may be of varying lengths, as in the application of analgesics. Risk measures are determined using the relative risk and the excess risk to assess drug safety. The latter has important public health policy significance for decision making about the safety of a drug. The model depends on a simple counting process and allows for the consideration of concomitant variables which can likewise exert an influence on the absolute risk. Hazard estimates are derived by the maximum likelihood method. Three possible approaches to the planning and analysis of studies of drug safety are discussed: cohort studies, case-cohort studies, and case studies. The case study represents an approach which requires only data from the individuals in which an adverse reaction has occurred. The different sampling designs are illustrated using data from a study investigating the etiology of wound healing disorders. PMID- 8455049 TI - The influence of sex and diabetes mellitus on survival following acute myocardial infarction: a community-wide perspective. AB - The objective of this report was to examine the effects of sex and diabetic status on in-hospital mortality and 12 year survival following hospital discharge among 4109 patients hospitalized between 1974 and 1986 with acute myocardial infarction. Sixteen general hospitals in the Worcester, MA, standard metropolitan statistical area were included. The age-adjusted in-hospital case-fatality rate was significantly higher in diabetic women (23.3%) than in non-diabetic women (18.9%) (p < 0.05) while no significant difference was noted among men. Over a 12 year follow-up period, the relative risk of dying among diabetic men was 1.56 times that for non-diabetic men (95% CI, 1.43, 1.68). Diabetic women were 1.57 times as likely to die as non-diabetic women (95% CI, 1.45, 1.73). Among non diabetic subjects, men had a 17% excess risk of death compared to women (95% CI, 1.09, 1.25). No significant difference in long-term mortality was noted among diabetic persons. Thus, the "female advantage" observed in the non-diabetic population was eliminated among the diabetic patients. Randomized clinical trials are needed in the diabetic population to identify specific therapies to reduce their increased risk of death. PMID- 8455050 TI - Application of a sequential t-test in a cohort nested case-control study with multiple controls per case. AB - Application of sequential analysis may avoid unnecessary experimentation and achieve economical use of available biomaterial stored in biological banks. When, as often happens in cohort case-controls studies, cases are scarce, it may be possible to use multiple control observations per case to increase the power of a test for detecting differences between cases and controls. Samples from a biological data bank were analysed. We compared results of a non-sequential analysis with results of sequential t-tests for 1 to 5 controls matched per case in a cohort nested case-control study. Simulations are performed to get an idea of the unreliability and the power of the sequential test. In general the sequential t-tests are too conservative with respect to the achieved power. Average sample numbers are lower for the sequential tests and decrease with multiple controls. More than 3 or 4 controls per case does not give a meaningful increase in efficiency. PMID- 8455051 TI - Comparison of analytic models for estimating the effect of clinical factors on the cost of coronary artery bypass graft surgery. AB - The cost of treating disease depends on patient characteristics, but standard tools for analyzing the clinical predictors of cost have deficiencies. To explore whether survival analysis techniques might overcome some of these deficiencies in the analysis of cost data, we compared ordinary least square (OLS) linear regression (with and without transformation of the data) and binary logistic regression with two survival models: the Cox proportional hazards model and a parametric model assuming a Weibull distribution. Each model was applied to data from 155 patients undergoing coronary artery bypass grafting. We examined the effects of age, sex, ejection fraction, unstable angina, and number of diseased vessels on univariable and multivariable predictions of costs. The significant univariable predictors of cost were consistent in all models: ejection fraction was significant in all five models, and age and number of diseased vessels were each significant in all but the OLS model, while sex and angina type were significant in none of the models. The significant multivariable predictors of cost, however, differed according to model: ejection fraction was a significant multivariable predictor of cost in all five models, age was significant in three models, and number of diseased vessels was significant in one model. All five models were also used to predict the costs for an average patient undergoing surgery. The Cox model provided the most accurate predictions of mean cost, median cost, and the proportion of patients with high cost. This study shows: (1) lower ejection fraction and older age are independent clinical predictors of increased cost of CABG, and (2) the Cox proportional hazards model shows considerable promise for the analysis of the impact of clinical factors upon cost. PMID- 8455052 TI - Can severity of symptoms be used as an outcome measure in trials of non-ulcer dyspepsia and Helicobacter pylori associated gastritis? AB - Most trials of non-ulcer dyspepsia (NUD) and Helicobacter pylori associated gastritis (HPAG) have not used validated methods of measuring symptoms. Three attributes are necessary for use of symptom severity scoring systems as outcome measures in clinical trials: reproducibility, responsiveness to change and validity compared to corroborating measures. The objective of this study was to establish that selected gastrointestinal symptoms recorded as a series of 5-point Likert Scales meet the 3 criteria for use as outcome measures in clinical trials. Patients with NUD (Helicobacter pylori-negative) and HPAG were studied. A preliminary assessment of 24 patients was used to select the 8 most frequently occurring and most severe symptoms. These symptoms were then scored in a further 55 patients to assess their utility as outcome measures. Observations were made at 3 time points, enrollment (T1), after 1 week with no intervention (T2) and after 4 weeks of therapy for either disease (T3). The study took place in a university hospital outpatient gastroenterology service. Symptom scores were reproducible before treatment (symptom scores at T1 and T2 were correlated), responsive (symptom scores changed after treatment between T2 and T3) and valid (symptom score changes corresponded to changes in general health status). Scoring of gastrointestinal symptom severity using 5-point Likert Scales satisfies the 3 criteria for use as outcome measures in clinical trials of NUD and HPAG. PMID- 8455053 TI - Predicting dementia from the Mini-Mental State Examination in an elderly population: the role of education. AB - Our study aimed to assess whether education affects the positive predictive value of the MMSE when it is used as a screening test for dementia. The MMSE has been consistently found to correlate with education and, at the same time, education is regarded by some researchers as being of potential etiological significance for dementia. In the present study, results on the MMSE from a community-based study in Sweden were compared with two standards: the clinical diagnosis of dementia and the Katz index of daily living activities. For both these comparisons, education did not substantially change the predictive ability of the MMSE. Our data, when compared with previous studies, show that the influence of education on the predictive ability of the MMSE varies in different populations. We conclude that differential MMSE cut-off points for different educational levels or adjustment techniques for education are not universally applicable. PMID- 8455054 TI - Subscapular and triceps skinfold thicknesses, body mass index and cardiovascular risk factors in a cohort of middle-aged employed men. AB - Associations of indices of adiposity with cardiovascular risk factors were examined in 1860 middle aged men employed by the Western Electric Company in Chicago in 1960 and 1961. Body mass index and subscapular and triceps skinfolds were examined for associations with systolic and diastolic blood pressure, serum cholesterol, and post-load serum glucose. Correlations of study variables measured one year apart suggest that triceps and subscapular skinfold measurements are less reproducible than body mass index, but more reproducible than measurements of systolic and diastolic blood pressure and serum cholesterol. Associations with blood pressure were stronger for body mass index than for skinfolds, and subscapular skinfold was associated with blood pressure independently of triceps skinfold, as well as age, heart rate, alcohol intake, and family history of cardiovascular disease. Body mass index was also generally more strongly related to serum cholesterol than skinfold measurements. Triceps skinfold was more strongly related to serum cholesterol than subscapular skinfold based on average values for the variables in 1960-61, but subscapular skinfold was more strongly related to one-year change in serum cholesterol. Subscapular skinfold was as strongly related to serum glucose as body mass index. This association was also independent of triceps skinfold and other variables. These analyses demonstrate positive associations of subscapular skinfold, an index of central adiposity, with blood pressure and serum glucose levels. Associations of subscapular and triceps skinfolds with serum cholesterol levels were not consistent in the cross-sectional and longitudinal analyses and require further investigation. PMID- 8455055 TI - Comparison of the prevalence of disability in two birth cohorts at the age of 75 years and over. AB - This research was designed to compare the prevalence of disability among cohorts born in 1903 or earlier (N = 348) and in 1913 or earlier (N = 586) at the age of 75 years and over in a geographically defined area. Disability was measured in terms of the number of ADL limitations according to Katz' index. The distributions of the cohorts according to Katz' index were essentially similar and the prevalence of disability was 29.2% in the earlier cohort and 34.8% in the later one. The occurrence of disability did not differ in logistic analysis (p = 0.08). The results suggest that the number of disabled old people increases in parallel to the growth in the elderly population. PMID- 8455056 TI - The Goldilocks dilemma in survey design and its solution. AB - A dilemma appears in the design of any survey with followups intended to detect the occurrence of an event. Suppose that, at followup, the event of interest can only be determined to have occurred since the previous interview (such is often the case, for example, with onset of dependent behavior in the aged). Then a followup which takes place too soon runs the risk of observing no or very few events, while a followup which is conducted after too long a wait might observe events in nearly every subject, and so be equally uninformative. Thus we would have what one investigator compares to Goldilocks dilemma: is the interval before followup too short, too long, or just right? The problem is multiplied when more than one followup is intended. As a partial solution, a technique is described here which provides guidance on the spacing of followup waves in a multiwave study, preventing possibly serious inefficiencies in study design. Data from the Massachusetts Health Care Panel Study (MHCPS) on functional dependence in the elderly are used for a demonstration. PMID- 8455057 TI - Instruments for neuroepidemiologic surveys. PMID- 8455058 TI - Critique of meta-analysis of second-line antirheumatic drugs. PMID- 8455059 TI - Sensitization of C6 glioma cells to radiation by staurosporine, a potent protein kinase C inhibitor. AB - The effect of staurosporine, a potent protein kinase C (PKC) inhibitor, on the sensitivity to radiation has been investigated in C6 glioma cells. Pretreatment of C6 cells with staurosporine at the concentrations over 1 nM resulted in an enhancement of sensitivity to irradiation. At a concentration of 5 nM, staurosporine caused significant radiosensitization of the cells, either it was administered 1) before and during irradiation, or 2) continuously before, during, and after irradiation, with a reduced D0 (the 37% survival dose) from 3.8 Gy to 2.9 Gy and 3.0 Gy, respectively, (p < 0.03). Since the viability of C6 cells was not affected by staurosporine alone at the concentrations tested, the radiosensitizing effect of staurosporine was considered to be mediated via suppression of PKC. Furthermore, another potent PKC inhibitor H-7, 1-(5 isoquinoline-sulfonyl)-2-methylpiperazine dihydrochloride, also sensitized C6 cells to irradiation, while HA1004, N-(2-guanidinoethyl)-5 isoquinolinesulfonamide hydrochloride a potent inhibitor for cAMP-dependent protein kinase, failed to affect the radiosensitivity in this cells. Therefore, staurosporine-induced sensitization of C6 cells to radiation may at least in part be mediated by its inhibitory activity for PKC. Staurosporine represents a new agent for radiosensitization and may prove usefulness in studying the mechanisms responsible for radio-resistance and -sensitivity in glioma cells. PMID- 8455060 TI - Phase II study of lonidamine plus radiotherapy in the treatment of brain metastases. AB - Twenty-nine patients received the cytotoxic radiosensitizing agent lonidamine before, during, and after cranial irradiation for brain metastases. One patient was ineligible (meningioma). In 28 eligible patients, median survival was 29 weeks (range, 2 to > 220 weeks). Nine patients (32%) survived > 1 year and 3 (11%) survived > 2 years. The major toxic effects of lonidamine were myalgias, nausea and vomiting, somnolence, and ototoxicity. There was no evidence that radiation skin toxicity or cerebral toxicity was increased by the addition of lonidamine. None of the patients experienced shrinkage of their extracerebral disease on lonidamine. Median survival duration in this study was at the upper limit of that reported in the literature for radiation alone, and the proportion of 2 year survivors was also higher than usual for radiation alone. Hence, further studies may be warranted. PMID- 8455061 TI - Schwannoma of the fourth ventricle presenting with hemifacial spasm. A report of two cases. AB - Two cases of cystic brainstem schwannomas protruding into the fourth ventricle are described. Both patients presented with hemifacial spasm. While there is only one previous case report of an intraventricular brainstem schwannoma, there has been no prior description in the literature of hemifacial spasm associated with such a tumor. The clinical, radiographic, surgical, and histopathological features of these tumors are elaborated. The relationship of hemifacial spasm to the various putative theories of origin proposed for intraparenchymal schwannomas is discussed. PMID- 8455062 TI - Diffuse primary leptomeningeal gliomatosis. AB - A 38 year old patient developed multiple cranial nerve palsy, seizures and progressive alteration in consciousness. CSF examination revealed tumor cells and a tentative diagnosis of leptomeningeal carcinomatosis from an unknown primary tumor was made. Treatment with intrathecal methotrexate and cranial radiation therapy was started without effect. At autopsy widespread leptomeningeal gliomatosis originating from a previously unknown astrocytoma of the hippocampus was found. PMID- 8455063 TI - Neurofibromatosis and optic pathways gliomas. PMID- 8455064 TI - The transdural extension of gliomas. AB - The extraneural spreading of gliomas is an infrequent occurrence which is not necessarily related to either tumor histology or site. This paper reports two cases, a glioblastoma and an oligodendroglioma, both presenting extradural diffusion. In the first case, where there was severe intracranial hypertension, the tumor found its way out from the neurocranium, far from the site of the operation, perforating the dura and the bone of the cranial base. In the second case, the operation may have facilitated the extraneural invasion. This unusual behaviour of glial tumors is probably less rare than presumed. It may go unnoticed if the attention is concentrated on the usually severe neurological syndrome which is present in these patients. PMID- 8455065 TI - A phase II evaluation of tamoxifen in unresectable or refractory meningiomas: a Southwest Oncology Group study. AB - Twenty-one patients with nonresectable refractory meningiomas were registered on a study giving tamoxifen 40 mg per M2 b.i.d. for four days, then 10 mg b.i.d. thereafter. Nineteen were eligible and evaluated for response. One patient (5%) achieved an MRI-documented partial response while two had a minor response measured on CT scan which was of short duration (4 and 20 months). Six patients (32%) remained stable for a median duration of 31 + months while ten (53%) demonstrated progression. Twenty-two percent (22%) reported subjective improvement though this did not correlate with objective improvement in all cases. At present, a definite recommendation for the use of tamoxifen in refractory meningiomas cannot be made. Further evaluation of hormonal therapy of meningiomas with a consensus for definition of endpoints for evaluation of response in view of the difficulty of evaluating radiologic findings with clinical outcome, is needed. PMID- 8455066 TI - Delivery of a novel nitrosourea, MCNU, to the brain tissue in glioma-bearing rats. Intracarotid versus intravenous infusion. AB - We observed the tissue delivery of a novel water-soluble nitrosourea, 1-(2 chloroethyl)-3-(methyl-alpha-D-glucopyranos-6-yl)-1-nitros our ea (MCNU) in rats bearing experimental brain tumors by conducting autoradiography on all. Prior to this study, the development of a streaming phenomenon was ascertained (and thus finding the optimum velocity for intra-arterial infusion) by 14C-iodoantipyrine (IAP) autoradiography. Furthermore, a single pass extraction value of MCNU was measured. At an arterial infusion rate of 0.2 ml/min., the streaming phenomenon was recognized but the tracer was fairly evenly distributed at a rate of 1.0 ml/min. On the other hand, the single pass extraction value for MCNU was 0.18 +/- 0.036 (mean +/- S.D., n = 3, under pentobarbital anesthesia). It was suggested that MCNU is very unlikely to be transported into the normal rat brain. We conducted 14C-MCNU autoradiography to observe tissue distribution of MCNU following its intra-arterial and intravenous infusions in a brain tumor model using rats. The normal side (the side where no infusions were given) and the cerebral cortex at the side affected by the tumor (the side where the infusion was given) showed hardly any uptake of 14C-MCNU in both the intra-arterial and intravenous infusion groups. The tumorous section was divided into the periphery and the center to measure tissue concentration of the tracer in each section. Compared against the cortical section, the periphery and the center showed significant increases in the concentration (approximately 11 to 15 times and 3 to 7 times, respectively, the figure for the cortical region) for both the intra arterial and intravenous groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455067 TI - Solitary brain metastasis 13 years after removal of renal adenocarcinoma. AB - We report a case of a patient who developed a single brain metastasis to the cerebellum 13 years after removal of a renal adenocarcinoma. The cerebellar metastasis was removed twice due to local recurrence one year after the first operation. The patient is alive and doing well 18 months after the second neurosurgical procedure. The metastasis was not associated with any other evidence of disease. Brain metastasis may present many years after removal of kidney adenocarcinoma and when not associated with other evidence of disease their operative treatment may carry a good prognosis. PMID- 8455068 TI - In vitro radiosensitivity of human medulloblastoma cell lines. PMID- 8455069 TI - The Energy Department's modest proposal. PMID- 8455070 TI - Energy Department molybdenum plan faltering. PMID- 8455071 TI - Physicians pan FDA plan for PET. PMID- 8455072 TI - FDG-PET in differentiating lymphoma from nonmalignant central nervous system lesions in patients with AIDS. AB - Structural imaging studies such as CT or MRI are not able to accurately differentiate infectious from malignant cerebral lesions in patients with AIDS. We studied 11 individuals with AIDS and central nervous system (CNS) lesions with 18F-fluoro-2-deoxyglucose (FDG) and positron emission tomography (PET). FDG-PET was able to accurately differentiate between a malignant (lymphoma) and nonmalignant etiology for the CNS lesions. Both qualitative visual inspection of the images as well as semiquantitative analysis using count ratios was performed and revealed similar results. FDG-PET may be useful in the management of AIDS patients with CNS lesions since high FDG uptake most likely represents a malignant process which should be biopsied for confirmation rather than treated presumptively as infectious. PMID- 8455073 TI - Characterization of gastric antral motility disturbances in diabetes using a scintigraphic technique. AB - In this study, food distribution in the stomach and gastric antral motor activity in patients with longstanding diabetes have been evaluated. With use of a standard gastric emptying test with an acquisition protocol and a refined Fourier algorithm to analyze the data, antral contractions have been characterized and gastric motility parameters were correlated to gastric retention in 20 diabetic patients with or without gastroparesis and in 10 healthy subjects. The results of this study show that, in longstanding diabetes, gastric emptying retardation is accounted for by a retention of food in the proximal stomach, which is reflected by a prolonged lag phase as well as by a reduction in antral motor activity that is determined by a decrease in the amplitude of the antral contractions. This study demonstrates that scintigraphy can noninvasively characterize abnormalities of food distribution in the stomach and provides information similar to that obtained from manometry. PMID- 8455074 TI - Effects of erythromycin on gastric emptying, alcohol absorption and small intestinal transit in normal subjects. AB - The effects of erythromycin on gastric emptying and intragastric distribution of a mixed solid/liquid meal, alcohol absorption and small intestinal transit were examined in eight male volunteers. Each subject received, in double-blind randomized order, either erythromycin as the lactobionate (3 mg.kg-1 i.v. over 20 min) or saline immediately before the consumption of a radioisotopically labeled test meal, which consisted of 330 g minced beef and 400 ml of orange juice containing ethanol (0.5 g.kg-1 body weight) and 10 g lactulose. Erythromycin increased the rate of total stomach emptying and proximal stomach emptying of both the solid and liquid components of the meal (p < 0.001), but slowed small intestinal transit (p < 0.01). Peak blood alcohol concentrations (p < 0.01) were higher after erythromycin, with a mean increase of 40%. There was a significant inverse relationship between peak blood alcohol concentrations and the 50% emptying time for the liquid component of the meal after saline (r = -0.70, p < 0.05), but not after erythromycin (r = -0.57, p < 0.1). The total area under the venous blood alcohol concentration time curve (i.e., total absorption) was greater (p < 0.01) after erythromycin. These results suggest that: faster emptying from the proximal stomach contributes to more rapid gastric emptying induced by erythromycin, erythromycin retards small intestinal transit and that erythromycin increases the total amount of alcohol absorbed as well as the rate of alcohol absorption. These latter effects are likely to reflect more rapid delivery of alcohol to the small intestine and reduced metabolism of alcohol by the gastric mucosa. PMID- 8455075 TI - A method of dynamic analysis of iodine-123-metaiodobenzylguanidine scintigrams in cardiac mechanical overload hypertrophy and failure. AB - Cardiac sympathetic neuronal degeneration accompanies mechanical overload heart failure. We hypothesized that sympathetic nerve and myocyte failure share a common etiology and that 123I-metaiodobenzylguanidine (MIBG) might provide a precise method of detecting failure in chronic mechanical overload. Our aim was to develop a method for the dynamic analysis of 123I-MIBG scintigrams which could yield a quantitative index of myocardial sympathetic neuronal function in this condition. We performed serial 123I-MIBG scintigraphy in 33 volunteers, 10 orthotopic cardiac transplant recipients and 26 patients with chronic mechanical overload of the left ventricle. We constructed a compartmental model in which total heart activity represents the sum of cardiac sympathetic vesicular and cytosolic pools. Patients with antecedent mechanical overload heart failure or myocardial dysfunction had accelerated myocardial egress of tracer that we ascribed to a specific impairment in vesicular storage rather than to a more rapid turnover of an intact vesicular pool. PMID- 8455076 TI - Gated SPECT with technetium-99m-sestamibi for assessment of myocardial perfusion abnormalities. AB - High counting statistics with 99mTc-sestamibi make gated SPECT imaging realistic. Information obtained with gated and nongated SPECT were compared in 83 subjects (20 normals, 63 patients) using a 1-day protocol (250 MBq [6 mCi] rest, 900 MBq [24 mCi] peak stress). Studies were acquired for eight frames/RR interval and formatted to a standard nongated study, a study consisting of diastolic (DIA) frames and dynamic functional studies. The right ventricle appeared more distinct in DIA than in nongated studies (p < 0.01). The left ventricular cavity was larger in DIA studies (p < 0.001), leading to more coronal slices with cavity (p < 0.001). A strong inverse relation between left ventricular cavity size in nongated studies and increase in cavity size and in number of coronal slices with cavity in DIA studies was found (r = -0.74 and -0.67, both p < 0.001). Severity (extent and degree) of perfusion abnormalities in rest and stress studies, assessed quantitatively in 50 patients (20 normals as reference), correlated highly in nongated and DIA studies (r = 0.98, p < 0.001). Severity of small and moderate sized perfusion defects showed a high degree of agreement in nongated and DIA studies, while severity of large defects was less pronounced in DIA studies (p < 0.05). In patients with subtle perfusion abnormalities, the results from DIA imaging agreed best with clinical data. PMID- 8455077 TI - Reproducibility of repeated measures of carbon-11-raclopride binding in the human brain. AB - Carbon-11-raclopride has been successfully utilized with PET to assess changes in endogenous dopamine concentration after pharmacological intervention in the living baboon brain. For similar studies to be done in humans, measurements of 11C-raclopride with no intervention need to be reproducible. In order to test the reproducibility (test-retest) of 11C-raclopride binding in the human brain, we performed repeated studies on two different days. Studies were done in five normal controls with no pharmacological intervention. Time-activity (%dose/cc) curves for 11C-raclopride in the basal ganglia (BG) and cerebellum (CBL) were highly reproducible with an average difference in peak uptake for repeated studies in the same individual of 4%. The BG to CBL ratio for the average activity concentration between 30 and 60 min showed differences that ranged from 7% to 8% between the repeated studies. Graphical analysis to obtain the distribution volume revealed intrasubject values that ranged from -9% to 7% for the ratio of the distribution volume in BG to that in CBL. These studies demonstrate that in order to use 11C-raclopride to measure an individual's change in relative dopamine concentration secondary to pharmacological or behavioral intervention, a change in striatal 11C-raclopride binding in excess of 10% is required. PMID- 8455078 TI - Simultaneous occurrence of rib infarction and pulmonary infiltrates in sickle cell disease patients with acute chest syndrome. AB - In order to determine if a relationship exists between rib infarction and the acute chest syndrome (ACS) in sickle cell disease patients, bone scans were reviewed in 55 episodes in 38 patients with pain of suspected osseous origin. A bone scan was positive for thoracic bone infarction if abnormally increased or decreased uptake was present in ribs, sternum or thoracic spine. Radiographs were considered to be positive for ACS if there was pulmonary infiltrate or pleural effusion in the absence of laboratory or clinical evidence of bacterial pneumonia. ACS by chest x-ray was present in 22 episodes, 21 of which showed evidence of infarction of the bony thorax on bone scan. Thoracic bone infarction occurred in the absence of chest x-ray changes in only 11 episodes. This association between bone infarction and radiographic ACS was statistically significant (p < 0.001, Fisher's exact test). A strong association exists between ACS and infarction of the bony thorax. It is possible that bone infarction leads to pain, hypoventilation and the clinical picture of ACS. PMID- 8455079 TI - Comparison of high specific activity (-) and (+)-6-[18F]fluoronorepinephrine and 6-[18F]fluorodopamine in baboons: heart uptake, metabolism and the effect of desipramine. AB - (-)-Norepinephrine is the principal neurotransmitter of the mammalian sympathetic nervous system and a major CNS neurotransmitter. The simple ring fluorinated derivatives of (-)- and (+)-norepinephrine [(-)- and (+)6-fluoronorepinephrine] and dopamine (6-fluorodopamine) have been labeled with 18F in high specific activity (2-5 Ci/mumol) and evaluated as tracers for (-)-norepinephrine. Comparative PET studies of (-) and (+)-6-[18F]fluoronorepinephrine [(-)-6 [18F]FNE and (+)-6-[18F]FNE] and 6-[18F]fluorodopamine (6-[18F]FDA) in the same baboon showed strikingly different kinetics in the heart. Analysis of plasma showed more rapid metabolism of 6-[18F]FDA with only 1%-2% of 18F remaining as parent tracer at 10 min after injection of 6-[18F]FDA, in contrast to 28% and 17% remaining after injection of (-) and (+)-6-[18F]FNE. No changes in vital signs were observed at any time during the study. Pretreatment with desipramine (0.5 mg/kg), a tricyclic antidepressant drug which interacts with a binding site associated with norepinephrine reuptake, markedly decreased cardiac uptake of 6 [18F]FDA and (-)-6-[18F]FNE. However, a greater blocking effect was observed for (-)-6-[18F]FNE. These studies show that (-) and (+)-6-[18F]FNE are similar to (-) and (+)-norepinephrine in their patterns of metabolism and clearance in the heart and that (-)-6-[18F]FNE is a promising tracer for endogenous (-) norepinephrine. PMID- 8455080 TI - Early myocardial clearance kinetics of technetium-99m-teboroxime differentiate normal and flow-restricted canine myocardium at rest. AB - Technetium-99m-teboroxime (CardioTec) is a promising new myocardial perfusion imaging agent. The purposes of this study were to define teboroxime clearance kinetics in normal and flow-restricted myocardium over a 1-hr period and to determine whether teboroxime kinetics are useful in detecting myocardial hyperperfusion. Accordingly, the circumflex arteries of 23 dogs were stenosed. By using miniature cadmium-telluride radiation detectors, myocardial teboroxime activities were continuously monitored in both the control and the stenosed zones. Myocardial clearance of teboroxime was modeled and found to be biexponential over 1 hr. A significant difference in myocardial clearance between the normal and stenosed zones (t1/2 = 4.5 +/- 0.9 min versus 10.2 +/- 2.6 min, respectively; p < 0.05) was observed for the first exponential phase (the first 5 min following initial uptake), but not for the second exponential phase (t1/2 = 160.7 +/- 35.9 min versus 140.4 +/- 27.4 min, respectively; p = ns). One hour fractional teboroxime blood clearance was 0.95 +/- 0.03, with most of the clearance occurring during the first 4 min. Gamma camera images of excellent quality demonstrated an initial defect with significant quantitative differential clearance over 1 hr. Thus, there are two phases of myocardial teboroxime clearance. During the early exponential clearance phase, teboroxime kinetics at rest may be able to differentiate between normal and hypoperfused myocardium. PMID- 8455081 TI - Vitamin C as a radioprotector against iodine-131 in vivo. AB - The capacity of vitamin C (ascorbic acid) to mitigate radiation damage resulting from the tissue-incorporated radionuclide 131I is examined. Spermatogenesis in mice is the experimental model and spermhead survival is the biological endpoint. When a small nontoxic amount of vitamin C was injected, followed by a similar injection of 131I, the 37% spermhead survival dose (D37) increased by a factor of 2.2 compared with the D37 in animals receiving only the radionuclide. Similar radioprotection was also observed when the animals were maintained on a diet enriched with 1% vitamin C (by weight). These results suggest that vitamin C may play an important role as a radioprotector against accidental or medical radiation exposures, especially when radionuclides are incorporated in the body and deliver the dose in a chronic fashion. PMID- 8455082 TI - The single-pass cerebral extraction and capillary permeability-surface area product of several putative cerebral blood flow imaging agents. AB - We have determined cerebral blood flow (CBF) and the single-pass cerebral extraction (E) of several putative agents for external imaging of CBF. Simultaneous measurements of blood flow and extraction were performed in 106 rats. For all agents, comparison of linear and exponential regressions of E on CBF indicates that this relationship can be described as linear over the range of flows studied. Analysis of covariance indicates that the extraction of 123I-IMP, 67Cu-PTSM and 99mTc-HMPAO is higher than that of 99mTc-Cl(DMG)3(2MP) and 99mTc ECD, particularly at flows above the normal range. Accordingly, for 123I-IMP, 67Cu-PTSM and 99mTc-HMPAO, the slope of the linear regression equation for the relationship between brain capillary permeability surface area product (PS) and CBF is higher than that for 99mTc-Cl(DMG)(3)2MP and 99mTc-ECD. PS varies as a linear function of CBF over the range of flows studied. At a CBF level that corresponds to normal regional CBF for human cortex, 0.5 ml/g/min, all the agents have a single-pass extraction of approximately 70% or greater. While all the agents detected changes in CBF in the normal to ischemic range, at higher flows 123I-IMP, 67Cu-PTSM and 99mTc-HMPAO showed substantially greater fidelity to true CBF than 99mTc-Cl(DMG)(3)2MP and 99mTc-ECD. PMID- 8455083 TI - Comparison of uptake, oxidation and lipid distribution of 17-iodoheptadecanoic acid, 15-(p-iodophenyl)pentadecanoic acid and 15-(p-iodophenyl)-3,3 dimethylpentadecanoic acid in normal canine myocardium. AB - The kinetics of 17-[123I]iodoheptadecanoic acid (IHDA), 15-(p [125I]iodophenyl)pentadecanoic acid (pIPPA) and 15-(p-[131I]iodophenyl)-3,3 dimethylpentadecanoic acid (DMIPPA) were investigated in normal canine myocardium. After simultaneous intravenous injection, myocardial biopsy specimens and samples of arterial blood were taken over 80 min. IHDA showed the highest myocardial uptake (995 +/- 248 dpm/mg.mCi versus pIPPA: 785 +/- 197 dpm/mg.mCi, ns) and the largest size of oxidation (74% +/- 4% versus pIPPA: 65% +/- 5%, p < 0.05). Myocardial activity of IHDA decreased with a half-time value of 11.2 min (pIPPA: 13.2 min). Phospholipids were the main lipid fraction into which IHDA was incorporated, whereas pIPPA was predominantly incorporated into triacylglycerols. DMIPPA myocardial activity remained constant during the assay period and instead of being oxidized, DMIPPA was mainly incorporated into triacylglycerols (55% +/- 12%). The myocardium-to-blood ratios of DMIPPA were greater than 10:1. The ratios at peak for IHDA and pIPPA were 4.1:1 and 3.9:1, respectively (both p < 0.0001 versus DMIPPA). In conclusion, differences have been found in the myocardial uptake, oxidation and lipid distribution of IHDA, pIPPA and DMIPPA. DMIPPA is a promising tracer for fatty acid uptake studies with single-photon emission computerized tomography because of its prolonged retention and high myocardium-to blood ratios. PMID- 8455084 TI - Sequential ten-second acquisitions for detection of gastroesophageal reflux. AB - We illustrate the importance of short imaging times during gastroesophageal (GE) scintigraphy to better image GE reflux while still obtaining clinically useful gastric emptying data. While most reflux scans are comprised of 30- or 60-sec sequential images, we advocate the use of 10-sec images to maximize the signal-to noise ratio of any radionuclide present in the esophagus. In the current case, clinically documented reflux of significant magnitude was missed during a study inadvertently performed using 60-sec frames, but subsequently detected using a 10 sec imaging protocol. PMID- 8455085 TI - Do diagnostic algorithms always produce a uniform lung scan interpretation? AB - Several algorithms have been devised to assist in the interpretation of ventilation-perfusion (V/Q) scans performed to diagnose pulmonary embolism. The degree to which adherence to a single algorithm facilitates diagnostic homogeneity among different readers, however, has been little investigated. We evaluated the individual variability in V/Q lung scan interpretation in a large, academic nuclear medicine division to determine the degree of interpretive heterogeneity among a group of physicians all using the same image interpretation algorithm. Ventilation-perfusion scan interpretive patterns and the diagnostic accuracy of individual physicians were evaluated using quantitative parameters to establish group norms and to detect variations from these norms. The performance of each reader was tracked over a 4 yr period. There was a significant variation in V/Q interpretive patterns and diagnostic accuracy between readers despite the attempted use of a uniform diagnostic algorithm. Subgroups of interpretive styles could be defined based on the percentage of intermediate (including both indeterminate and intermediate categories) scans read. Although there was significant variation in diagnostic accuracy among readers, there was no obvious correlation between accuracy and reading style except that the most nonstandard diagnostic patterns were associated with the most variable diagnostic accuracy. These data show a measurable variation in interpretive patterns and accuracy among multiple readers of V/Q scans despite attempted group adherence to an established diagnostic algorithm. PMID- 8455086 TI - Ictal SPECT using technetium-99m-HMPAO: methods for rapid preparation and optimal deployment of tracer during spontaneous seizures. AB - Ictal SPECT provides unique information for the clinician treating patients with refractory epilepsy and reveals insights into the pathophysiology of seizures. We describe our methods for the routine attainment of ictal images using 99mTc HMPAO. We have devised and implemented techniques for rapid reconstitution of 99mTc-HMPAO adjacent to the video-EEG monitoring suite such that the tracer can be rapidly injected into patients when spontaneous seizures occur. Our quality assurance data show that this can be done safely outside a nuclear medicine department. The clinical results in patients with temporal lobe epilepsy show that ictal injections (97% correct lateralization of focus, 0% incorrect) are more sensitive and accurate compared to interictal studies (48% correct, 10% incorrect), demonstrating that the implementation of these techniques is worthwhile. PMID- 8455087 TI - Correction and characterization of scattered events in three-dimensional PET using scanners with retractable septa. AB - Large sensitivity increases are realized in positron emission tomography when the interplane septa are removed and all lines of response acquired. Unfortunately, three-dimensional acquisition results in a large increase in scatter fraction which prevents accurate quantitation. By acquiring short two-dimensional scans prior to three-dimensional ones, scatter distributions can be estimated from differences between lines of response common to both datasets. This initial scatter distribution can be further modified to approximate scatter in the entire three-dimensional dataset. The method was validated with phantom measurements in which absolute activity concentrations were known in all compartments. Following scatter correction, a four-compartment phantom that was nonuniform in activity and density, both axially and transaxially, gave activity concentrations of 0.45 +/- 0.02, 0.31 +/- 0.02, 0.01 +/- 0.01 and 0.01 +/- 0.01 microCi/cc for compartments containing 0.43, 0.29, 0.0 (air) and 0.0 (water) microCi/cc, respectively. Thus, scatter distributions for complex sources can be estimated from image data without lengthy Monte-Carlo simulations. When activity distributions vary slowly with time, this method can be used to correct for scatter in three-dimensional patient studies. PMID- 8455088 TI - Methods for improving quantitation of putamen uptake constant of FDOPA in PET studies. AB - To estimate the striatal uptake constant of [18F]-L-6-fluorodopa (FDOPA) in humans, we studied two methods that can account for the image resolution and the background level of FDOPA. These two methods utilize information obtained from multiple ROIs varying in size around the putamen and from profiles crossing the middle of the putamen. The estimation of the uptake constant was based on a model of one-dimensional activity variation. Simulated data were used to evaluate the adequacy of these two methods. Parametric images of FDOPA uptake constants were generated using Patlak analysis for five studies in normals and were then analyzed with the two methods. Results from the simulated data indicated a good agreement between the estimated values and the true simulated values. Results from studies in normals show stable estimates of the FDOPA uptake constant that are not affected by image resolution. The two methods were not sensitive to the misplacement of ROIs and profiles. PMID- 8455089 TI - Bone marrow dosimetry for radioimmunotherapy: theoretical considerations. AB - In most implementations of radioimmunotherapy, the red marrow is the dose limiting organ. Estimates of the radioactivity concentration in this organ are usually based on blood sampling or bone marrow biopsy. This work presents a simple equation which may be used to calculate the red marrow-to-blood activity concentration ratio given the hematocrit and the red marrow extracellular fluid fraction of a patient. Also presented are a series of equations which may be used to correct the activity concentration in bone marrow biopsies for bone, yellow marrow and blood contamination. Assuming a hematocrit of 0.47 and a red marrow extracellular fluid fraction of 0.19, the predicted red marrow-to-blood activity concentration ratio is 0.36. This value is consistent with experimental studies. Depending upon the characteristics of the bone marrow biopsy sample, the red marrow activity concentration may be underestimated by a factor of 1.5-5. The correction factor for an "average" biopsy is 2.73. If the cortical bone cap is removed before the sample is weighed and counted, the correction factor is 1.92. PMID- 8455090 TI - Radiation dose to the upper spine from therapeutic administrations of iodine-131 sodium iodide. AB - Thyroid cancer patients sometimes receive conventional external irradiation to the neck in addition to radioactive iodine therapy. In these situations, knowledge of the radiation dose already received by the spine in the neck area from the radioiodine administration can be an aid in treatment planning. This paper gives an estimate of the radiation dose to the upper spine from administration of 3700 MBq of 131I-sodium iodide. Monte Carlo codes used to estimate radiation dose from internal emitters usually give absorbed doses to the whole spine or marrow. One such code was modified to give a dose only to the upper spine region near the thyroid. Calculations assumed a thyroid uptake of 10% of administered activity and retention with a 35-hr effective half-time. Activity in the remainder of the body was assumed to clear with a 6-hr half-time to urine. Under these assumptions, the dose to this upper spine region was about 200 mGy. PMID- 8455091 TI - A unified approach to quantification by kinetic analysis in nuclear medicine. PMID- 8455092 TI - Application of the effective dose equivalent to nuclear medicine patients. The MIRD Committee. PMID- 8455093 TI - Occupational physicians and environmental medicine. AB - Physicians who practice environmental medicine seek to identify and to prevent patient and population exposures that cause adverse human health outcomes. Epidemiologic, toxicologic, clinical, and public health skills essential to this enterprise are indistinguishable from those of the occupational physician. Several important controversies illustrate the essential role of occupational physicians in environmental health science and policy, including environmental asbestos, dioxin, electromagnetic fields, and carcinogenicity testing. Our continuing involvement in "environmental" issues is predicted by three conditions, each unlikely to change. The human remains the animal of greatest interest; the "natural" experiment will have been performed (however unwittingly); and the work site will continue to provide that first and clearest setting for measuring the outcome. Therefore, residency training must be expanded so that future occupational and environmental physicians will recognize their fundamental role in environmental health. The results of our industry cross factory walls with ease. So must our efforts. PMID- 8455094 TI - Global issues in environmental medicine. AB - This overview will discuss a number of the issues posed by the challenge of international environmental health. The reasons that environmental problems occurring elsewhere in the world are of importance to occupational and environmental physicians in North America include the interconnectedness of the biosphere of our planet so that environmental alterations in one part of the globe can have an adverse outcome on our health and well-being; the often high levels of pollution and environmental degradation elsewhere provide an opportunity to determine and predict adverse consequences of environmental agents pertinent to protecting our own health; and, most importantly, our own ability to provide assistance in helping economic development occur in a setting of low risk of environmental pollution. PMID- 8455095 TI - Accepting the environmental medicine challenge. PMID- 8455096 TI - Beryllium disease screening in the ceramics industry. Blood lymphocyte test performance and exposure-disease relations. AB - We identified nine new cases of biopsy-confirmed chronic beryllium disease among 505 employees and ex-employees in a company that had manufactured beryllia ceramics from 1958 through 1975. Of tests commonly used in medical surveillance, only a confirmed blood beryllium lymphocyte transformation test had a high positive predictive value for beryllium disease (100%). However, two beryllium disease cases had either a normal or inconsistently abnormal blood test and were identified for diagnostic workup by abnormal chest radiograph. The only risk factor for beryllium disease was beryllium exposure; smoking or allergic history did not affect risk. Degree of beryllium exposure was associated with disease rates, which ranged from 2.9% to 15.8% for beryllia-exposed subgroups. One case of beryllium disease occurred in a "dust-disturber" who did not report past beryllium exposure and who began employment 8 years after commercial beryllia production had stopped. Our data support efforts to prevent beryllium disease by lowering beryllium exposures and to identify subclinical and early disease by broad-based medical surveillance using the blood beryllium lymphocyte test and chest radiograph in beryllium-using industries. PMID- 8455097 TI - Comparison of physical health benefits utilization. Mental and physical health claimants, 1989 and 1990. AB - Research has indicated an association between mental health problems and physical illness, including higher physical health benefits utilization among persons with a mental health diagnosis. We hypothesized that mental health claimants will have higher covered health benefits and be more likely to make physical health claims than physical health claimants. The data for the study included all health benefits claims for 1989 and 1990. The results indicated that mental health claimants have higher total covered benefits and higher covered benefits in a number of diagnostic categories. In addition, the findings revealed a greater likelihood to make any health claim as well as a claim for several diagnostic categories among persons with a mental health diagnosis. The study indicates the need for coordination between mental health and physical health benefits cost management. PMID- 8455098 TI - An evaluation of chronic methylene chloride exposure. AB - Various groups including the Occupational Safety and Health Administration, Environmental Protection Agency, and Consumer Product Safety Commission have expressed concern over methylene chloride and its possible effects on human health. A group of employees exposed to relatively high levels of methylene chloride (average = 475 ppm 8-hour time-weighted average) for greater than 10 years were compared to a similar nonexposed group of employees for selected health parameters. All were participants in an employee health monitoring program. Selected questions evaluating cardiac and neurologic health effects revealed no differences between the two groups. Likewise, hematologic assessment also revealed no clinically significant differences between the two groups for SGOT(AST), SGPT(ALT), total bilirubin, and hematocrit. Therefore, it appears that chronic exposure to even high levels of methylene chloride produces no difference in symptoms or adverse health effects in this population as judged by selected liver, cardiac, and neurologic health parameters. PMID- 8455099 TI - Exposure to TMXDI (meta) aliphatic isocyanate and TMI (meta) unsaturated aliphatic isocyanate. Clinical and immunological evaluation of 96 workers. AB - We evaluated 96 workers employed at facilities that manufacture or use TMXDI (meta) aliphatic isocyanate and TMI (meta) unsaturated aliphatic isocyanate. We used immunoglobulin (Ig) and IgG serum antibody enzyme-linked immunosorbent assay (ELISA) studies and a questionnaire designed to identify symptoms compatible with work-related syndromes such as asthma and hypersensitivity pneumonitis. There were no workers with immunologically induced disease due to TMI isocyanate or TMXDI isocyanate nor were there any workers whose questionnaires suggested new onset of asthma. Approximately 40% of workers experienced some irritant symptoms, mostly upper respiratory or ocular. One worker had low level IgE antibody against TMXDI-HSA but had no work-related respiratory symptoms. Very low-level IgG against TMI-HSA or TMXDI-HSA was present in 7% of workers, all of whom were in the high-exposure category. PMID- 8455100 TI - Health practices before and after a work-site health screening. Differences among subpopulations of employees. AB - The workplace has evolved as a venue for health promotion programs that attempt to reduce employees' risk behaviors and encourage positive health practices. There is little information about the efficacy of such programs for selected subpopulations of employees. Questionnaires designed to measure health practices were administered before and 10 weeks after a work-site health screening. Results indicated that subpopulations had distinctly different patterns of health behaviors both before and after the health screening, and the pattern of variability was inconsistent across various health practices. In general, females and salaried employees had healthier practices than males and hourly employees, respectively. Several interesting interactions between participation status and gender and occupational status need further investigation. Understanding health behaviors of subpopulations may provide insights for implementation of work-site programs that will enhance health-promoting behaviors of all employees. PMID- 8455101 TI - Hospital sharps-disposal system I. PMID- 8455102 TI - Hospital sharps disposal system II. PMID- 8455103 TI - Neurobiology of techno-stress. PMID- 8455104 TI - Evaluation of chemically sensitive patients. PMID- 8455105 TI - High yield of chest radiography in walk-in clinic patients with chest symptoms. AB - PURPOSE: To assess the yield of chest radiography among a group of symptomatic adults presenting to a walk-in clinic. PATIENTS AND METHODS: Outpatients presenting to a walk-in clinic for evaluation of cough, shortness of breath, or pleuritic chest pain were interviewed by nurses who recorded clinical data pertaining to the present illness and past medical history. Chest radiographs were then obtained prior to physician evaluation. RESULTS: A total of 221 patients were enrolled in the study; 97% were men and the mean age was 62 (+/- 10.3) years. New clinically important radiographic abnormalities, defined as those necessitating acute intervention and/or follow-up evaluation, were identified for 77 (34.8%) of the 221 patients studied. Abnormalities included 39 (17.6%) cases of infiltrates, 23 (10.4%) cases of nodules or mass lesions, and 19 (8.6%) cases of cardiomegaly or congestive heart failure. Evaluation of clinical data obtained during the triage interview revealed no statistically significant difference between those patients with and those without new radiographic abnormalities on their chest x-rays. CONCLUSION: Adult patients similar to those described in this study who present to a walk-in clinic with a chief complaint of cough, dyspnea, or pleuritic chest pain have a high likelihood of having new clinically important abnormalities found on their chest radiographs. Since patient characteristics did not predict which patients were more likely to have abnormal findings, the practice of obtaining chest radiographs for such individuals at the time of triage and prior to physician evaluation appears justified. PMID- 8455106 TI - Screening flexible sigmoidoscopy: patient attitudes and compliance. AB - OBJECTIVE: To measure patients' expectations and attitudes about screening flexible sigmoidoscopy and their discomfort during the procedure, and to identify factors affecting compliance among patients scheduled for sigmoidoscopy. DESIGN: Patient survey at the time sigmoidoscopy was ordered and again one week after the procedure was performed. SETTING: An academic general internal medicine practice. PATIENTS: 105 consecutive patients scheduled for screening flexible sigmoidoscopy. MAIN RESULTS: Seventy-five percent of patients (79/105) scheduled for sigmoidoscopy complied with the procedure. Compliance was higher among men and among patients who had family histories of colon cancer. Although many patients experienced moderate to extreme embarrassment (27%), discomfort (42%), and pain (31%), patients experienced less embarrassment (p = 0.03) and pain (p = 0.02) than they had expected. Patients aged 65 years and older were twice as likely as younger ones (52% versus 25%) to experience moderate to extreme pain (p = 0.04). Only 1.4% of patients reported that they would probably not have the test again. CONCLUSION: Although flexible sigmoidoscopy is an uncomfortable procedure for some patients, especially those aged 65 and older, in general it is not as bad as patients expect and most would have the test again. Therefore, rather than assuming sigmoidoscopy is too uncomfortable for all patients to tolerate as a screening test, clinicians should inform their patients about the potential benefits and risks of sigmoidoscopy and about what the patient can expect during the procedure, thus enabling the patient to make an informed decision about whether to undergo screening sigmoidoscopy. PMID- 8455107 TI - Unique educational program in critical care medicine for the general internist. AB - OBJECTIVE: To determine the effect of a unique educational program in critical care medicine on the attitudes, knowledge, and skills of general internists who care for critically ill patients. DESIGN: Comparison of objective assessments and self-assessments obtained before and after the one-year educational program. SETTING/PARTICIPANTS: Eighteen general internists practicing in a 350-bed university-affiliated community teaching hospital. RESULTS: After the program, the internists felt significantly more competent in, knowledgeable about, comfortable with, and satisfied with caring for critically ill patients than they did when completing the precourse self-assessments (p < 0.05). Participants felt particularly more comfortable with managing ventilator patients and leading the advanced cardiac life-support team (p < 0.05). Comfort levels for other commonly performed critical care procedures did not vary. No significant change in knowledge test scores was noted from before to after the one-year program (61% vs 60%). Residents and nurses rated the internists' overall ability in critical care medicine to be the same as that of senior medical residents. They also favorably rated the internists on humanism, teaching skills, and interpersonal interactions. Residents also appreciated the decrease in their night call because of the program. CONCLUSIONS: This unique educational program increased comfort and satisfaction of general internists caring for critically ill patients. The program was well accepted by residents and nurses because of favorable interaction with the internists and a decrease in resident night-call responsibility. This curriculum is recommended to other teaching hospitals. PMID- 8455108 TI - The effect on resident attitudes of regulatory policies regarding pharmaceutical representative activities. AB - OBJECTIVE: To determine the effect on resident attitudes of policies regarding pharmaceutical representative interactions with residents. DESIGN: Cross sectional survey. SETTING: National sample of U.S. family medicine residencies. PARTICIPANTS: Three hundred seventy-eight residents from 14 randomly selected programs. Seven programs had written policies and restrictions (restricted programs), and seven had no such restriction or guideline (free programs). MEASUREMENTS AND MAIN RESULTS: The authors assessed resident attitudes regarding the perception of benefit from pharmaceutical representative activities, the usefulness of various sources of drug information, and the appropriateness of accepting gifts from a pharmaceutical representative. There were 265/378 respondents (70% response rate). Residents from restricted programs reported fewer benefits from pharmaceutical representative interactions and were less likely to feel that acceptance of gifts was appropriate. The amount of exposure to pharmaceutical representatives was positively correlated with perceived benefit and negatively correlated with ratings of appropriateness of gift acceptance. CONCLUSION: Regulatory policies can influence resident attitudes and perceptions. Training programs should develop written policies to help guide resident-pharmaceutical representative interactions. PMID- 8455110 TI - Data and the internal medicine houseofficer: alumni's views of the educational value of a residency program's research requirement. AB - The authors surveyed 112 recent alumni and 92 current residents (70% responded) at a residency program that requires original research. Most alumni felt that the research project was a valuable learning experience, particularly in improving their abilities to critically review the medical literature. Almost a third felt that it had influenced their career choices (academic medicine vs private practice). The overall learning value of no other residency program component was rated significantly higher than that of the research project. While 65% of current residents supported making the senior resident research project optional, 64% of alumni opposed this change (p < 0.0001). These results support requiring formal oral presentations and encouraging original research projects as a part of residency training. PMID- 8455109 TI - A questionnaire for patients' evaluations of their physicians' humanistic behaviors. AB - OBJECTIVES: To determine what behaviors patients perceive as reflecting a physician's humanistic qualities, to develop an instrument for patients to use to assess the humanistic behaviors of their own physicians, and to compare patient assessment of residents' humanistic behaviors with patient satisfaction and the assessment of attending physicians. DESIGN: Cross-sectional descriptive study, using patient interviews and questionnaires, and evaluations of residents by attending physicians. SETTING: Inpatient medical service in a tertiary care teaching hospital and in a primary care internal medicine clinic. PARTICIPANTS: Six medical interns and six medical residents, 119 medical patients in the hospital, and 111 patients in the internal medicine clinic. MEASUREMENTS AND MAIN RESULTS: The 25-item Physicians' Humanistic Behaviors Questionnaire (PHBQ) was developed from patients' statements about important humanistic behaviors. The mean PHBQ scores were 4.46 +/- 0.22 (mean +/- SD, on a scale of 1 to 5) in the clinic and 4.18 +/- 18 in the hospital (p = 0.003). The Spearman's rank correlations between the PHBQ and the Medical Interview Satisfaction Scale (MISS) were r = 0.8741 (p < 0.001) in the hospital and r = 0.8751 (p < 0.001) in the internal medicine clinic. The Spearman's rank correlation between the hospital PHBQ and the attending physician evaluations (for the six residents for whom the authors had complete data) was r = 0.5753 (p = 0.232). CONCLUSIONS: Patients can evaluate the humanistic behaviors of their physicians using the PHBQ. There is good correlation between the PHBQ and patient satisfaction, which supports the validity of the PHBQ. The relative lack of agreement between patients and attending physicians suggests different observations, criteria, or standards. The higher ratings from patients in the clinic compared with those from patients in the hospital suggest that residents' behaviors are different or that patients have different observations, criteria, or standards in the two settings. Therefore, a complete assessment of residents' humanistic behaviors may require sampling in both settings. PMID- 8455111 TI - The impact of educational loan burden on housestaff career decisions. AB - The past decade has seen declining interest in primary care medicine and a dramatic increase in the cost of a medical degree. Seventy-nine percent of housestaff in an internal medicine residency program responded to a survey to determine whether medical school loan burden was related to career choice in a primary care field or specialty area. Overall mean indebtedness was $45,185 (median $40,000). Thirty-eight percent of residents with debts < $40,000 chose a career in primary care, compared with 10% with debts > $40,000 (chi square = 9.44, p < 0.01). Fourteen percent of those with debts < 40,000 and 59% with debts > $40,000 stated that financial conditions had a moderate to marked impact on their career decision making. Excessive loan burden has a significant influence on residents' career decision making and a negative influence on choosing careers in primary care internal medicine. PMID- 8455112 TI - Effects of a night float system on housestaff neuropsychologic function. AB - To examine the effect of a night float call system (NFS), a battery of neuropsychologic tests was administered to housestaff after call during an overnight call system (ONCS), and the results were compared with the results obtained during a NFS. Although NFS housestaff were less sleep-deprived, results of tests of psychomotor function were not different. Importantly, both groups had high depression, hostility, and anxiety scores. NFS housestaff had small but significantly lower depression scores, which, if not due to time of year, may represent a positive effect of the NFS. Future investigation should be directed at clarifying the aspects of residency training that adversely affect housestaff mood. PMID- 8455114 TI - Immune thrombocytopenic purpura: current concepts. PMID- 8455113 TI - Exercise and physical activity in the adult population: a general internist's perspective. PMID- 8455115 TI - Evaluation of humanistic qualities and communication skills. PMID- 8455116 TI - Residency reform and health care research. PMID- 8455117 TI - Sleep disturbance in primary care patients with fatigue. PMID- 8455118 TI - Consensus on care for critically ill patients. PMID- 8455119 TI - Diagnosis and treatment of inferior oblique palsy. AB - We present the work-up and treatment for 25 patients with inferior oblique palsy, including 2 with bilateral inferior oblique palsy and 23 with unilateral inferior oblique palsy. Nineteen patients were adults over the age of 21 years, and six were children under the age of 10 years. Sixteen adults and two children underwent CT scanning of the head. All scans were normal. Eight adults also underwent MRI evaluation of the head. These also were all normal. All adults had a negative Tensilon test for myasthenia gravis. The majority presented with a head tilt to the side of the paretic muscle. None of these patients complained of tilting images, but incyclotorsion was measurable in all cases that were tested. The most important conclusion from this study is that inferior oblique palsy is a benign entity, with none of these patients having a brain tumor or myasthenia gravis. PMID- 8455120 TI - Results of cryotherapy at different locations for retinopathy of prematurity. AB - Fifty eyes with stage 3 plus retinopathy of prematurity (ROP) were treated with cryotherapy. The avascular retina (AR) only was treated in 15 eyes with a mean extent of 8.3 hours of stage 3 ROP; the ridge extraretinal fibrovascular proliferation complex (REFP) was treated in 17 eyes with a mean extent of 7.5 hours; and both locations (BL) were treated in 18 eyes with a mean extent of 7.7 hours. Ninety-three percent to 94% of eyes in each group had less than grade III retrolental fibroplasia (RLF-Reese). However, 87% of the AR treated eyes, 59% of the REFP treated eyes, and 44% of the BL treated eyes had less than grade II RLF. Whether more than or less than 8 hours of stage 3 ROP was treated, significantly better results occurred in the AR group than the BL group (.02 < P < .05) and a statistical trend suggests that treating the AR is more effective than treating the REFP (.1 < P < .2). PMID- 8455121 TI - Retinal hemorrhage following lensectomy and anterior vitrectomy in children. AB - Lensectomy and anterior vitrectomy were performed on 13 eyes of 10 consecutive children, aged 10 years or less, with congenital or acquired nontraumatic cataracts or subluxed lenses. Operative eyes were examined prospectively to determine the incidence and natural course of hemorrhagic retinopathy following lens extraction. Flame-shaped retinal hemorrhages occurred in five eyes of four patients within 24 hours of surgery. In addition, a small vitreous hemorrhage was seen in one of these patients. All hemorrhages cleared within 3 weeks postoperatively. No statistically significant correlation was found between the occurrence of hemorrhage and patient age, race, sex, or duration of surgery. We conclude that retinal hemorrhage following lensectomy and anterior vitrectomy in children may occur more commonly than previously recognized. PMID- 8455122 TI - Visual results of lens-sparing vitreoretinal surgery in infants. AB - Lens removal is routinely performed when vitreoretinal surgery is done in infant eyes. We performed vitreous surgery in nine infants (10 eyes) without removing the crystalline lens. Surgery was done to correct vitreoretinal pathology involving the macula. Indications for surgery included: 1) tractional retinal detachment secondary to retinopathy of prematurity, familial exudative vitreoretinopathy, or congenital retinal folds; and, 2) nonclearing preretinal hemorrhage secondary to shaken-baby syndrome. Surgical objectives were achieved in all cases. Postoperatively, 8 of 10 eyes showed no evidence for lens opacification with a median follow-up period of 8 1/2 months (range, 5 to 19 months). Two eyes with retrolental adhesions due to stage 5 retinopathy of prematurity developed progressive cataracts and light perception vision. Six of seven eyes without lens opacity had vision of 20/2400 or better (median = 20/800) as measured by Teller acuity methods. Lens-sparing surgery may be performed with favorable anatomic and functional results in eyes with vitreoretinal disease posterior to the equator. Lens preservation may optimize optical rehabilitation and stimulation of the developing visual system. PMID- 8455123 TI - Breast-feeding and optimal visual development. AB - The goal of the present study was to determine whether dietary supply of omega-3 essential fatty acid (EFA) influences visual development in healthy pre-term and full-term infants. Visual status was examined in human milk-fed infants (ample dietary omega-3 EFA supply) and corn oil-based formula-fed infants (no dietary omega-3 EFA; standard formula prior to 1987). At 57 weeks postconception (4 months adjusted age), both pre-term and full-term human milk-fed infants had significantly better visual evoked potential (VEP) and forced-choice preferential looking (FPL) acuity than formula-fed infants. Acuity was correlated with a dietary omega-3 sufficiency index from red blood cell membranes obtained at 57 weeks postconception. At 36 months, full-term human milk-fed children had significantly better random dot stereo acuity and letter matching ability than formula-fed children. Stereo acuity and performance on the letter matching test were correlated with a dietary omega-3 sufficiency index from red blood cell membranes obtained at 4 months. These results suggest that dietary omega-3 fatty acids play an important role in visual development. PMID- 8455124 TI - The importance of controlled illumination in color vision testing in a pediatric ophthalmology clinical practice. AB - The AO-HRR pseudoisochromatic plates are commonly used for color vision testing in pediatric ophthalmology; however, the recommended procedure for obtaining proper illumination (a completely darkened room and standard illuminant) is typically not followed. To evaluate the role of the illuminant in clinical testing with the AO-HRR, 132 children, ages 3 to 16 years, were tested with and without the recommended illuminant (MacBeth Easel Lamp) and with the self illuminated APT-5 Color Vision Tester. Twenty-two failed the AO-HRR with the recommended illuminant; 28 failed the AO-HRR without the illuminant. Only 13 failed the APT-5. The Cochran Q test for three related samples showed that the differences among the three groups were significant (Q = 17.1, P < .001). Diagnostic evaluation following clinical screening indicated that the differences among the tests were primarily due to false alarms, which were greatest without the recommended illuminant and least with the APT-5. These results demonstrate the importance of controlled illumination in color vision testing, either by using the recommended illumination with the AO-HRR or a self-illuminated test such as the APT-5. PMID- 8455125 TI - Bilateral retinal embolization associated with intralesional corticosteroid injection for capillary hemangioma of infancy. AB - A 2-month-old female infant underwent intralesional corticosteroid injection for a capillary hemangioma that was causing amblyopia of the right eye from ptosis, globe displacement, and astigmatism. Forty-eight hours after the injection, the infant's parents noted that she was visually inattentive. On examination, she could not fixate or follow with either eye, and an afferent pupillary defect was present in the left eye. Ophthalmoscopy showed scattered areas of intraretinal hemorrhage in the right eye and extensive preretinal and intraretinal hemorrhages in the left eye. Ten months after injection, the hemangioma had greatly regressed, and visual acuity in the right eye was felt to be normal. The left eye had unsteady fixation with a persistent afferent pupillary defect and macular scarring. Retrograde flow of the corticosteroid suspension through the hemangioma's feeder vessels, probably originating from both ophthalmic arteries, is the most likely explanation for this complication. PMID- 8455126 TI - Ectopic (extradural) meningioma of the orbit: a report of two cases in children. AB - Meningiomas arising from the optic nerve or secondarily invading the orbit from the intracranial cavity are uncommonly encountered in children. Ectopic (extradural) meningiomas are exceedingly rare orbital tumors that do not originate from either the optic nerve or the intracranial meninges. We evaluated and treated two boys aged 7 and 10 years with probable primary ectopic (extradural) orbital meningiomas. Both patients presented with a gradual onset of progressive, painless proptosis. In addition, computed tomographic scans demonstrated involvement of the superomedial orbit without bony erosion or hyperostosis, but with expansion of the adjacent sinus. Neither tumor demonstrated attachment to the optic nerve or intracranial extension at the time of surgery. Both patients were successfully treated with complete surgical excision. Evaluation did not reveal the presence of neurofibromatosis in either child. PMID- 8455127 TI - The ophthalmologic manifestations of the cardio-facio-cutaneous syndrome. AB - The cardio-facio-cutaneous (CFC) syndrome is an uncommon multiple congenital anomalies/mental retardation syndrome whose major manifestations are congenital heart defects, relative macrocephaly, stunted growth, ectodermal dysplasia, characteristic facial appearance, and psychomotor developmental delay. All described cases were sporadic and cytogenetically normal. We report three additional patients with this diagnosis. All three patients developed strabismus, requiring extraocular muscle surgery. Two of our patients also had nystagmus. Combining the 18 previously reported cases with our additional 3, 9 of 21 had strabismus, 10 of 21 had ptosis, and 6 of 21 had nystagmus. Ophthalmic craniofacial abnormalities of hypoplastic supraorbital ridges, prominent epicanthal folds, and antimongoloid slant of the palpebral fissures were also common features contributing to the characteristic facies described for this syndrome. The ophthalmologist could aid in the diagnosis and treatment of these patients because of the prominent ophthalmologic symptomatology of the CFC syndrome. PMID- 8455128 TI - Worth vs Polarized four-dot test. AB - A direct comparison between the Worth four-dot (W4D) and Polarized four-dot (P4D) flashlights is reported in a randomized trial on 107 unselected patients greater than 2.5 years old. The primary outcome variable was the interpretable response rate. Secondary outcomes were response time and age of test failure. There were 29 patients who failed to complete the W4D test, but only 10 patients who could not complete the P4D test, giving interpretable response rates of 73% and 91%, respectively (p < .001). The P4D test was found to be less dissociative and easier to administer. It also had a higher detection rate for fusion. We recommend its use as a tool in the clinical evaluation of binocular sensorial states. PMID- 8455129 TI - Episodic exotropia from lateral rectus neuromyotonia--appearance and remission after radiation therapy for a thalamic glioma. AB - Sixteen months after radiation therapy for a moderately anaplastic astrocytoma of the thalamus, a 7-year-old boy developed spontaneous episodic contractions in his left lateral rectus muscle. During these episodes, lasting 10 to 30 seconds and occurring 20 or more times a day, he had exotropia, limitation of adduction, and retraction of the left globe. This phenomenon peaked in duration and frequency at 14 months and gradually disappeared after 22 months. As this case confirms, radiation injury to the abducens nerve can cause ocular neuromyotonia, resulting in episodic strabismus. Our case also illustrates that this condition can disappear completely after many months. PMID- 8455130 TI - Molluscum contagiosum of the eyelid and infraorbital margin--a clinicopathologic study with light and electron microscopic observations. PMID- 8455131 TI - Orbital pseudotumor in the differential diagnosis of pediatric uveitis. PMID- 8455132 TI - Horizontal transposition of the vertical rectus muscles for treatment of ocular torticollis. AB - In most instances, a head tilt to either shoulder is caused by hypertropia or cyclotropia and responds well to conventional surgical strengthening or weakening operations on the cyclovertical muscles. Occasionally, an ocular head tilt occurs in the absence of cyclovertical strabismus, in association with congenital nystagmus or without an apparent cause. We have successfully treated four of five such patients by surgically rotating the eye(s) around the sagittal axis. This was accomplished by horizontal transposition of the vertical rectus muscles. No complications were encountered. We present this method as a viable alternative to other surgical approaches to rotate the eyes around their sagittal axis. PMID- 8455133 TI - Preparation of poly(2-hydroxyethyl methacrylate)-collagen composites. AB - Linear and three-dimensional polymer composites were prepared on the basis of poly(2-hydroxyethyl methacrylate)--pHEMA--and collagen. Their biological properties were tested by in vitro as well as in vivo methods. The composite material (unlike pure pHEMA) supported myoblast adhesion as well as their fusion into multinuclear myotubes in vitro. The three-dimensional polymer composites stimulated a new bone formation after their intraosseal implantation in dogs and pigs. The biomaterial itself was degraded in the host organism, in contrast to stable pHEMA. PMID- 8455134 TI - Photografting of albumin onto dimethyldichlorosilane-coated glass. AB - 4-Azido-2-nitrophenyl albumin (ANP-albumin) was prepared by displacing the fluoro group of 4-fluoro-3-nitrophenyl azide (FNPA) by an amino group of albumin. Photolysis of phenyl azides of ANP-albumin was studied by Fourier-transform infrared (FTIR) spectroscopy. The band of phenyl azide disappeared completely after a 12-min exposure to long wave UV light (366 nm), and the photolysis was first-order. Albumin was grafted onto dimethyldichlorosilane-coated glass (DDS glass) by photolysis of the azido groups of ANP-albumin without any premodification of the surface. The albumin-grafted DDS-glass was characterized by determining the relative amount of nitrogen resulting from the grafted albumin on the surface using electron spectroscopy for chemical analysis (ESCA). The amount of nitrogen increased when the concentration of ANP-albumin in the adsorption solution increased up to 0.1 mg/ml. As the solution concentration increased above this value, the amount of nitrogen decreased. The platelet resistance of the albumin-grafted surfaces was evaluated by measuring the number of adherent platelets and the extent of activation that was quantitated by the area of platelets spread on the surfaces. The maximum platelet-resistant effect was observed when the ANP-albumin was adsorbed for more than 50 min at the solution concentration ranging from 0.05 to 10 mg/ml. PMID- 8455135 TI - Relationship of surface characteristics to cellular attachment in PU and PHEMA. AB - Adhesion characteristics of fibroblastic baby hamster kidney (BHK) cells and epithelial Madine Darby kidney (MDBK) cells on polyurethane (PU) and polyhydroxyethylmethacrylate (PHEMA) based surfaces have been studied. PU surfaces were prepared by a classical solvent-casting procedure of Pellethane solution that contains different types of solvents, i.e., THF, dioxane and their compositions. PHEMA based surfaces were obtained by bulk polymerization of respective comonomers (HEMA, acrylic acid, AA, and dimethylaminoethylmethacrylate, DMAEMA) in the presence of the crosslinker. Thus, a number of polymeric surfaces were obtained with different surface charges (COO- and NH+4) and with different surface free energies in a range between 60-82 ergs/cm2. Surface properties of these membranes were characterized by equilibrium water contents, air and octane contact angles, surface free energies, SEM photographs and ATR-FTIR spectra. Interactions of BHK and MDBK cells with the surfaces were examined in stationary culture conditions which were carried out in MEM supplemented with fetal calf serum. The observations strongly suggested that the chemical and/or physical properties of membrane surface and morphology of the cell control the degree of cell adhesion to the PU and PHEMA based membranes. PMID- 8455136 TI - Bioactive polymers 68--controlled release of neomycin-furazolidone bicomponent system from xanthan hydrogel. AB - The neomycin-furazolidone-xanthan complex has been synthesized. Neomycin is covalently linked to xanthan, while furazolidone is inserted in the hydrogel formed by the reaction between neomycin and xanthan. The content of neomycin and furazolidone depends on the drug rate in the reaction medium. Thus, a zero-order kinetics is obtained for the release of both neomycin and furazolidone in basic medium. The complex's antimicrobial activity is intensified. PMID- 8455137 TI - Ultrasonically mediated drug delivery. PMID- 8455138 TI - Direct detection of HIV-1 RNA in epidermal Langerhans cells of HIV-infected patients. AB - Human Langerhans cells (LC) are bone marrow-derived, HLA-DR+, CD1a+, and CD4+ dendritic antigen-presenting cells found in stratified squamous epithelia. As other members of the dendritic leukocyte family, to which they belong, LC have been reported as targets for HIV-1 infection. The aim of the present study was to investigate whether HIV-1 RNA is expressed in epidermal LC of HIV-1-infected patients. Bulk epidermal cell (EC) suspensions were prepared from skin of nine recently deceased AIDS patients and 11 seronegative controls. Purified LC (94 +/- 4% HLA-DR+ cells with no CD3+ cells, as assessed by flow microfluorimetry analysis) and LC-depleted EC were obtained by immunomagnetic separation using an anti-CD1a monoclonal antibody. Samples were analyzed for the presence of HIV-1 RNA by reverse transcription of a spliced mRNA region of the tat gene, followed by polymerase chain reaction amplification. HIV-1-spliced RNA was detected in LC from 6 of 9 patients examined, whereas LC-depleted EC fractions from the same patients were all negative. The results indicate that epidermal LC from HIV seropositive patients actively transcribe HIV-1 proviral DNA, further supporting the hypothesis that HIV productively infected LC could serve as a reservoir of the virus in the epidermis and as a source for the infection of T lymphocytes. PMID- 8455139 TI - HIV-1 gp120 and NMDA induce protein kinase C translocation differentially in rat primary neuronal cultures. AB - Exposure of rat cortical neurons to the human immunodeficiency virus type 1 (HIV 1) coat protein gp120 in vitro causes a rise in the intracellular Ca2+ level and a subsequent translocation of protein kinase C (PKC) from the cytosol to the membrane. Such a translocation persists for at least 2 h, but only in cultures with media not depleted of endogenous glutamate. Enzymatic degradation of glutamate in the medium by the enzyme glutamate-pyruvate transaminase (GPT) abolishes the long-lasting effect of gp120 on the association state of PKC; under this incubation condition the translocation period is < 1 h. Memantine and the ganglioside GM1 prevent N-methyl D-aspartate receptor-mediated long-term translocation of PKC and gp120-mediated neurotoxicity (in the absence of GPT); they have no effect on short-term translocation of PKC. We suggest that gp120 caused neuronal death involves an indirect sensitization step of the NMDA receptors, which ultimately induces neuronal death. PMID- 8455140 TI - Limited proteolytic digestions identify common structural features of HIV-1 Tat proteins expressed during infection from alternatively spliced mRNAs. AB - Although multiple forms of the HIV-1 Tat protein are synthesized during infection from alternatively spliced mRNAs, only 72 amino acid residues encoded in the first Tat exon are necessary for full transactivation activity. We used limited proteolytic digestions of proteins expressed in vitro to study the structures of three Tat proteins from isolate HXB2: 72R Tat (first Tat exon); 86R Tat (first and second Tat exons), Tev or TNV (first Tat exon plus Env and Rev exons). For the 86R and Tev proteins, either trypsin or chymotrypsin cleaved the majority of carboxyl residues from the first exon. Moreover, when released from carboxyl residues, the first exon of 86R and Tev was relatively resistant to subsequent proteolysis. The entire 72R Tat protein was relatively resistant to proteolysis. The protease-resistant first exon in all Tat proteins was abolished by EDTA treatment, suggesting that divalent cations are required for its conformation. Our results suggest that the first exon in the 86R, 72R, and Tev proteins is folded into a similar structure which, as defined by partial proteolysis, acts as a single biochemical domain. PMID- 8455141 TI - Human monoclonal antibodies to the V3 loop of HIV-1 gp120 mediate variable and distinct effects on binding and viral neutralization by a human monoclonal antibody to the CD4 binding site. AB - Interactive effects between human monoclonal antibodies specific for the V3 loop (257-D and 447-D) and an epitope within the CD4 binding site (F105) of HIV-1 gp120 were evaluated for neutralization of viral cytopathogenicity and binding to HIV-infected cells. Regardless of antibody pair, only additive effects were observed in neutralization of MN and SF2 virus though each antibody alone had potent neutralizing activity on these strains. Significant cooperativity was observed between F105 and 447-D in neutralization of RF. Relatively high concentrations (> 100 micrograms/ml) of each individual antibody are required for partial neutralization (25--40%) of RF. Coincubation with 10 micrograms/ml of each antibody increased neutralization activity 3--4-fold more than predicted for additive effects alone. No enhancement was seen upon coincubation of F105 with 257-D which does not neutralize RF. Antibody interactions with native antigen on HIV-infected cells was measured by flow cytometry. Results were consistent with neutralization results in the majority of flow cytometry experiments; however, enhanced binding did not necessarily predict enhanced neutralization. These data support the notion that either a conformational change occurs with binding of V3 loop antibodies which enhances the binding and neutralizing activity of antibodies directed to the CD4 binding site of gp120 or vice versa, or new antigenic sites are exposed by the V3 loop antibodies on cell surfaces and virions. Of importance, cooperativity is observed even at very low antibody concentrations. PMID- 8455142 TI - Zidovudine therapy of HIV-1 infection during pregnancy: assessment of the effect on the newborns. AB - Zidovudine (ZDV) administration during pregnancy has been suggested for the prevention of mother-to-child HIV-1 transmission. Reliable levels of the drug have been observed in the fetus and in the newborn. Seven HIV-1-infected pregnant women who declined to have abortions and whose immunological status required antiretroviral treatment were administered oral ZDV 18 mg/kg in four daily doses, the initial dose being administered anytime from the 16th to the 30th week of gestation up until the time of delivery. Follow-up of the seven infants from birth with a mean duration of 22 months (range 16-32 months) revealed mild drug related toxicity: anemia in two infants and macrocytosis in all seven, both conditions resolved by the second month of life. All infants remained HIV-1 seronegative, according to the 1987 CDC classification, and all stayed clinically well. Other virological parameters including virus culture, in vitro antibody production, and polymerase chain reaction, repeatedly performed in the infants, remained negative. Although none of the mothers transmitted HIV-1 infection to the offspring, the size of this study and the relatively low transmission rate (13%) in Europe do not permit us to draw a definite conclusion about treatment efficacy in preventing maternal-fetal transmission. However, the drug caused only limited toxicity among the infants, and its administration to large numbers of mothers in treatment trials should be considered relatively safe for both mother and child. PMID- 8455143 TI - Cardiac involvement in human immunodeficiency virus-infected patients. AB - Heart involvement in patients with AIDS has been described in autopsy and clinical series, but the true incidence in HIV-infected patients is not clear. A prospective study was done on 101 unselected HIV-infected patients (71 with AIDS and 30 with pre-AIDS) and 24 healthy controls to assess the prevalence of cardiac abnormalities. Assessment included physical examination, electrocardiogram, two dimensional echocardiogram, and Doppler studies. At least one abnormality was detected in 41 (40.6%) HIV-infected patients vs. 3 (12.5%) in controls (p = 0.003). Echocardiographic abnormalities were detected in 29 (28.7%) HIV-infected patients and 3 (12.5%) controls (p = 0.04). There were no significant differences in abnormalities on physical examination, electrocardiogram, or Doppler studies. Only six (5.9%) HIV-infected patients had abnormal cardiac findings on physical examination. We found no correlation between HIV staging, CD4 cell count, acute illness, or severity of illness and the presence of cardiac abnormalities. Cardiac abnormalities in HIV-infected patients are more frequent than in healthy controls, but most abnormalities are of no significant clinical consequence. PMID- 8455144 TI - Unsafe sexual behavior and alcohol use at the event level: results of a national survey. AB - In recent years, several researchers have suggested that the use of alcohol in conjunction with sexual activity significantly increases the probability that unsafe or risky sexual behavior will occur. However, the majority of studies examining this relationship have utilized general measures of drinking frequency and sexual behavior, and are therefore unable to establish whether the drinking and risky sex occur on the same occasion. In this study, adult respondents in a national survey were asked about the circumstances of two sexual encounters: their most recent sexual experience and their most recent encounter involving a new sexual partner. The characteristics of encounters that involved and did not involve drinking are described. The results showed that although encounters with new partners were more likely to involve alcohol, the presence of alcohol in the event was not significantly associated with risky sexual activity. The occurrence of risky sexual behavior was predicted by a number of individual and situational variables, including sexual attitudes, drinking habits, and personality characteristics. These findings suggest that the relationship between drinking and risky sex is the result of a complex interaction among personality, situational, and behavioral factors. PMID- 8455145 TI - The potential for transmission of human immunodeficiency virus through human bites. AB - We review the potential for human immunodeficiency virus (HIV) transmission by human bites. HIV may be present in saliva, although infrequently and at low levels. In prospective studies, 13 people bitten by HIV-infected individuals have remained HIV seronegative. Only two cases have been published in which HIV transmission through bites may have occurred. Both blood-contaminated and cell free saliva may contain HIV. The presence of blood in the saliva may potentially heighten the theoretical risk of HIV transmission through human bites. We have estimated the risk of HIV transmission through human bites and have compared it with the known risks of HIV seroconversion by needle stick (0.3-0.5%). Needle sticks, on average, could transmit 20 times more HIV-infected cells than would a human bite. We conclude that the transmission of HIV through human bites is biologically possible but remains unlikely, epidemiologically insignificant, and, as yet, not well documented. PMID- 8455146 TI - Prevalence of Toxoplasma infection in a cohort of homosexual men at risk of AIDS and toxoplasmic encephalitis. AB - The purpose of this study was to characterize the epidemiologic, clinical, and laboratory parameters of a cohort of men at risk of AIDS-associated toxoplasmic encephalitis. One hundred seventeen (11%) of the 1,073 participants at the time of enrollment into the Chicago Multicenter AIDS Cohort Study (MACS) were seropositive for Toxoplasma antibodies. Significant differences in prevalence of antibodies between African-American, Hispanic, or white men were not observed (p = 0.49). One hundred one (86%) of the 117 antibody-positive participants had at least one follow-up serology performed and 6 (6%) of the 101 had a significant rise in IgG antibody titer on subsequent visits. Five of six participants with a significant rise in titer were also seropositive for HIV-1 at entry or seroconverted during the study. A trend toward higher IgG Toxoplasma titers and prevalence of IgM antibodies in participants seropositive for HIV-1 was observed, but the differences did not reach statistical significance. There was no evidence that the presence of Toxoplasma infection predisposed to development of CD4+ depletion or AIDS. None of the 183 individuals in the cohort who developed AIDS and who were seronegative for Toxoplasma antibodies developed toxoplasmic encephalitis. In contrast, of the 13 persons who developed AIDS and who were positive for Toxoplasma antibodies, 5 (38%) developed toxoplasmic encephalitis. Prevalence of Toxoplasma antibodies in the MACS population was independent of HIV 1 serostatus. Toxoplasma infection does not appear to predispose to progression of HIV-1 infection. The risk of development of toxoplasmic encephalitis in persons with AIDS and chronic Toxoplasma infection may have been underestimated by previous retrospective studies. PMID- 8455147 TI - Low and stable HIV seroprevalence in pregnant women in Shaba province, Zaire. AB - Sentinel serosurveillance for HIV infection has been carried out in Shaba province, Zaire, among consecutive pregnant women attending antenatal clinics from 1989 to 1991. There were four surveillance sites (three urban and one semiurban), at which a total of 13 surveillance studies were made of 4,205 women. Overall, 3.1% were HIV seropositive. There were no significant differences in HIV seroprevalence between surveillance sites, and HIV seroprevalence did not increase at any of the surveillance sites during the 2-year period of study. Since changes in the population studied did not occur between surveillance studies, it is believed that the observed stable trend reflects stable HIV seroprevalence rates in the general adult population of the surveillance sites. Collateral HIV seroprevalence data were available from 8,725 blood donors at 20 sites (six urban, 14 rural) in the province, who had an overall HIV seroprevalence of 4.6%. The higher HIV seroprevalence rate among blood donors was probably due to selection bias, since HIV seroprevalence rates in two blood banks, which relied nearly exclusively on replacement donors, were 2.7 and 2.8%, our best estimate for HIV seroprevalence in the three cities where blood banks exist and where no surveillance studies were carried out. The stable and relatively low HIV seroprevalence rates in Shaba province are in sharp contrast with the rapidly increasing and much higher rates in neighboring Zambia and other East African cities. Reasons for this discrepancy are unclear, and their eludication may yield critical information for HIV prevention programs. PMID- 8455148 TI - Blood transfusion as a major risk factor for HTLV-I infection among hospitalized children in Gabon (Equatorial Africa). AB - To study the risk factors for HTLV-I infection of African infants living in a high seroprevalence area, a survey was conducted among hospitalized children and their mothers in Franceville, southern Gabon. A total of 610 children (6 months to 14 years old) from 555 families and 434 mothers participated in the study. HTLV-I seroprevalence was 7.1% in the mothers and 2.8% in the children. No increase by age was observed in the children. Significantly more children with sickle cell anemia (11 of 57, or 19.2%) were infected than others (1%) (Fisher's exact test p < 0.001). Of the 13 seropositive infants (C+) whose mothers were tested, six (43%) had a seropositive mother (M+) [p < 0.001, prevalence ratio (PR) 10.12, 95% CI 3.40-30.35, attributable risk (AR) 0.55]. Risk factors for nonmaternally acquired HTLV-I infection were previous blood transfusion (Fisher's exact test p < 0.001, PR 15.74, CI 5.20-47.60, AR 0.71) and hospital admission. In a hospitalized pediatric population in Gabon mother-to-child transmission and blood transfusion (because of sickle cell disease) were equally implicated in HTLV-I infection. Control of HTLV-I infection in children in Africa requires prevention of both vertical and transfusion-associated transmission, which may be exceedingly difficult in developing countries. PMID- 8455149 TI - Rhodococcus equi infection in HIV-infected patients. PMID- 8455151 TI - Living situation of women with AIDS. PMID- 8455150 TI - The success and failure of condom use by homosexual men in San Francisco. PMID- 8455152 TI - Changes in HIV-2 seroprevalence in Cape Verde, west Africa. PMID- 8455154 TI - A study of the antimicrobial properties of impression tray adhesives. AB - Three impression tray adhesives were tested for their antimicrobial actions on three bacteria strains used for disinfectant studies. The colony forming unit (CFU) counts from plating the adhesive-exposed bacteria showed a significant reduction in number compared with the CFU of the controls. Statistical analyses confirmed the significant reduction (p < 0.05) for all but one test case. Proper infection control procedures should always be followed, but the added benefits of disinfection by impression tray adhesives can help prevent cross contamination. PMID- 8455153 TI - Comparison of the performance on prosthodontic criteria of several alternative alloys used for fixed crown and partial denture restorations: Department of Veterans Affairs Cooperative Studies project 147. AB - In a 10-year, multicenter, double-blind clinical trial, comparisons of the clinical behavior of crown and fixed partial denture restorations were made between a gold alloy and four less costly alternative alloys. The endpoints of interest were (1) the development of unacceptable ratings on any of 11 individual prosthodontic criteria and an overall rating, (2) the removal of the restoration, and (3) an event combining unacceptable overall rating and restoration removal. Each of 630 patients had two restorations completed, one from gold-palladium alloy and the other from one of four alternative alloys. The patients were enrolled during a period of 3 1/2 years, with some patients followed up as long as 10 years after restoration. Analysis of the endpoints showed that one of the alternative alloys was significantly poorer than the other materials for certain criteria. PMID- 8455155 TI - Fluorescence of dental porcelain. AB - This study of the fluorescence of natural enamel and of dental ceramics shows the fluorescence of ceramics not containing rare earths decreases when the color saturation increases; the fluorescence of samples of the same shade guide are not homogenous; some guides show a strong green fluorescence; and two shade guides of the same origin can present completely different fluorescence. The cementing medium can affect the fluorescence of a ceramic prosthesis. PMID- 8455156 TI - Physical property comparison of 11 soft denture lining materials as a function of accelerated aging. AB - Soft denture-lining materials are an important treatment option for patients who have chronic soreness associated with dental prostheses. Three distinctly different types of materials are generally used. These are plasticized polymers or copolymers, silicones, or polyphosphazene fluoroelastomer. The acceptance of these materials by patients and dentists is variable. The objective of this study is to compare the tensile strength, percent elongation, hardness, tear strength, and tear energy of eight plasticized polymers or copolymers, two silicones, and one polyphosphazene fluoroelastomer. Tests were run at 24 hours after specimen preparation and repeated after 900 hours of accelerated aging in a Weather-Ometer device. The data indicated a wide range of physical properties for soft denture lining materials and showed that accelerated aging dramatically affected the physical and mechanical properties of many of the elastomers. No soft denture liner proved to be superior to all others. The data obtained should provide clinicians with useful information for selecting soft denture lining materials for patients. PMID- 8455157 TI - Comparison of the adhesive strength of a BIS-GMA cement to tin-plated and non-tin plated alloys. AB - This study compared the tensile bond strengths of two base metal alloys and two noble metal alloys, tin-plated and non-tin-plated, with an adhesive resinous cement. Two tin platers were compared for their effectiveness in enhancing the composite resin-to-metal bond. Cylinders of the alloys were bonded end to end with the adhesive cement, thermocycled for 24 hours, stored in distilled water for 27 days, and tested for tensile bond strength. The mean bond strengths and mode of failure were recorded, and scanning electron micrographs were recorded for subjective evaluation. Significant differences were demonstrated between the non-tin-plated and the tin-plated noble alloys and base metal alloys. PMID- 8455158 TI - A resin-bonded conversion attachment for the reversal of key/keyway position in a nonrigid connector. PMID- 8455159 TI - Preparation of the dowel space. PMID- 8455160 TI - Modification of a stock orbitale indicator assembly as an aid to achieve proper cast orientation. PMID- 8455161 TI - Fabrication of a space-stippled vacuum-formed bleaching or fluoride carrier tray. PMID- 8455162 TI - Customizing work authorization order. PMID- 8455163 TI - Marginal accuracy of metal ceramic restorations with porcelain facial margins. AB - This study compared porcelain facial margins made with the direct-lift technique using high-fusing shoulder porcelains and the platinum foil technique with conventional body porcelain. Marginal accuracy was measured directly and the marginal sharpness computed by the software program MacDraft. Both Vita high fusing shoulder porcelain and Vita SM 90 porcelain produced restorations that had significantly smaller mean facial marginal openings than crowns created with platinum foil. However, the SM 90 porcelain recorded significantly greater cross sectional or internal marginal discrepancies than the other two techniques (p < 0.05). Externally, the shoulder porcelains followed the facial rounding of the stone die; thus porcelain marginal roundings can be manifested as either negative roundings or underextensions and positive roundings or overextensions. The lack of marginal sharpness of porcelain facial margins may be influenced more by the die material rather than by the marginal porcelain or the technique. PMID- 8455164 TI - Effect of adhesive luting agents on the marginal seating of cast restorations. AB - This study determined the effect of new adhesive luting agents on the marginal seating of cast restorations. Standardized preparations were completed on freshly extracted premolars, impressions were made, and complete metal veneer crowns were cast with a base metal alloy. The castings were placed on their respective teeth and the extent of marginal opening was recorded. They were then assigned to a luting agent group: glass ionomer cement (GI), polycarboxylate cement (PC), microfilled BIS-GMA composite resin with NPG-GMA/PMDM dentinal bonding agent (GMA + NPG), microfilled BIS-GMA/phosphate ester composite resin (GMA/PE), or zinc phosphate cement (ZP). The castings were cemented and marginal openings remeasured. ANOVA revealed that the cement groups were similar before cementation (p 0.35) but were different after cementation (p < 0.0001). Tukey's multiple comparisons test identified statistically similar groups that were different from other groups and ranked them from lesser to greater marginal opening: (GI, ZP, PC) (GMA/PE, GMA + NPG). PMID- 8455165 TI - The philosophies of dowel diameter preparation: a literature review. AB - This article reviewed the literature regarding the diameter of dowels and identified three distinct philosophies of dowel space preparation. One group advocated the narrowest diameter for fabrication of a dowel to a desired length. Another recommended a dowel space with an apical diameter equal to one third of the narrowest dimension of the root at the terminus of the dowel. A third group advised that at least 1 mm of sound dentin should surround the entire surface of the dowel. A combination of the one third and 1 mm minimal philosophies yielded a practical guideline for dowel space preparation, particularly in aged teeth. Requiring a definite amount of tooth structure surrounding the dowel, while adhering to the one third proportion, indicated upper limits on both the diameter and length of the dowel. These calculated limits served as convenient starting points in selecting a specific style of dowel and assisted in determining whether additional measures are warranted to enhance dowel retention. PMID- 8455166 TI - Effect of post design on resistance to fracture of endodontically treated teeth with complete crowns. AB - The effect of post design on the fracture resistance of endodontically treated premolars restored with cast crowns was examined in vitro. The experimental model used cast posts and cores to test the effect of post design in a post-core system with identical rigidity. Samples loaded on an Instron testing machine until failure revealed that post design did not influence the fracture resistance of endodontically treated premolars restored with complete cast crowns. There was also no statistically significant difference between restored teeth with or without cast posts and cores. PMID- 8455167 TI - Decomposition rate of hydrogen peroxide bleaching agents under various chemical and physical conditions. AB - The decomposition rate of 30% hydrogen peroxide was measured when hydrogen peroxide was mixed with 36% hydrochloric acid and anaesthesia either in 5:5:1 solution and in a solution of 20% sodium hydroxide at temperatures of 16 degrees to 20 degrees C and at 45 degrees C, respectively. The effect of ferris chloride on the decomposition of hydrogen peroxide was also observed. The decomposition of 30% hydrogen peroxide in sodium hydroxide solution was faster than that in the mixture of hydrochloric acid and ether at low temperature (16 degrees to 20 degrees C). The decomposition of hydrogen peroxide was accelerated by heat. The experiment implies that the bleaching effect of hydrogen peroxide can be achieved without heat by use of a sodium hydroxide solution. Further study on the rationale of the compound of the McInnes solution (hydrogen peroxide, hydrochloric acid, and anaesthesia ether mixed at a ratio of 5:5:1) is needed. PMID- 8455168 TI - Osteoporosis and reduction of residual ridge in edentulous patients. AB - The relationship between the height of the mandibular residual ridge and the severity of osteoporosis in elderly edentulous patients was investigated. The height of the mandibular residual ridge was measured by use of the mental foramen on panoramic radiographs. The severity of osteoporosis was determined by examining frontal and lateral radiographs of the vertebrae. All of the patients received a blood analysis. The correlation coefficient between age and the height of residual ridge was -0.38, which was statistically significant (p < 0.01). The residual ridge in women was lower than that of men, showing a statistical significance (p < 0.01). The correlation coefficient was -0.42 between degree of severity of osteoporosis and the height of the residual ridge, which was significant (p < 0.01). The parathyroid hormone level was high in the patients with a low residual ridge, and the calcitonin (CT) level was low. This study indicates that osteoporosis strongly affects reduction of the residual ridge in edentulous patients. PMID- 8455169 TI - Effect of tinfoil substitute contamination on adhesion of resin denture tooth to its denture base. AB - At least one manufacturer claims that contamination of denture teeth with tinfoil substitute during processing is not detrimental. The purpose of this study was to determine whether tinfoil substitute contamination has any significant effect on the bond strength between acrylic resin denture teeth and their processed acrylic resin base. Eighty acrylic resin maxillary central incisors were processed to denture base material. The experimental group had the denture tooth ridgelap area contaminated with tinfoil substitute. The control group was not contaminated. The bond strength of the two groups was tested. The results indicate that contamination with tinfoil substitute significantly reduces the bond strength of acrylic resin denture teeth bonded to their denture base. PMID- 8455170 TI - Osseointegrated implant rehabilitation of the previously irradiated mandible: results of a limited trial at 3 to 7 years. AB - The use of osseointegrated dental implants in patients with defects of the head and neck acquired as a result of ablative surgery for malignancy is an accepted and valuable extension of the well-documented use of these implants for the treatment of edentulism. In patients who have received ionizing radiation as part of tumor therapy, the use of dental implants is poorly documented. A limited trial of 21 Branemark implants placed in the previously irradiated mandibles of four patients is reported here. The implants have been in place and functioning for periods of 3 to 7 years. No implants have been lost. Patient selection, treatment, and complications encountered are discussed. Guidelines for further use of osseointegrated implants in patients with previously irradiated mandibles are suggested. PMID- 8455171 TI - Surgical implant stent: a design modification and simplified fabrication technique. AB - The buccal and lingual placement and parallelism of endosseous implants is important for the implant surgeon and the restorative dentist alike. A modified surgical stent to aid in implant placement and a simplified technique for making the stent is described. PMID- 8455172 TI - Simplified fabrication of orbital prostheses using posterior attachment for the artificial eye. AB - The ocular component of an orbital prosthesis can be held firmly during fabrication by attaching a plastic needle cover with autopolymerizing acrylic resin to the posterior surface of the eye in the wax-sculpted prosthesis. This index is subsequently embedded in the master cast. Compared with other techniques described in the literature, this technique spares the corneal surface of the artificial eye and allows duplicate fabrication of silicone orbital prostheses in nonmetal durable molds. PMID- 8455173 TI - Prosthodontic management of temporomandibular disorders and orofacial pain. AB - Guidelines for advanced education in prosthodontics describe specific competency levels. The complex nature of temporomandibular disorders (TMD) and oral facial pain requires a multidisciplinary team. However, the multifactorial nature of this malady places some aspects of this disease beyond the traditional education of a prosthodontist. The management goals for the prosthodontist as a member of a TMD team are patient comfort, occlusal stability, and/or the complex restoration of teeth. PMID- 8455174 TI - Sleeve design for a fixed partial denture. AB - A new sleeve design of a cemented cast retainer for a posterior fixed partial denture to improve retention with minimal tooth reduction while sustaining the original occlusal relationships is described. PMID- 8455175 TI - Kinesiographic and electromyographic assessment of the effects of occlusal adjustment therapy on craniomandibular disorders by a double-blind method. AB - Fifty-one patients with craniomandibular disorders were divided into two groups. One group underwent mock occlusal adjustment, the other was treated with adjustments to remove significant slides and nonworking-side interferences. Both groups received identical counseling. Kinesiographic and electromyographic assessment showed no significant difference between the two groups. PMID- 8455176 TI - Effect of age and sex on craniomandibular disorders. AB - The purpose of this study was to investigate the effect of age and sex on craniomandibular disorders. A total of 195 subjects were examined, 148 women and 47 men. The range of age was 16 to 70 years. Clinical and anamnestic examination data established the ratio of women to men as 4:1. The prevalence of clicking, headache, teeth-clenching, hypomobility, difficulty in mastication, and neuromuscular symptoms was greater among young women than in other age and sex groups. There was a statistically significant correlation between severity of symptoms and age among women, and a relative decline by age in the prevalence of symptoms for both sexes. Finally, younger patients showed a greater prevalence of neuromuscular symptoms, whereas older patients had more peripheral symptoms. PMID- 8455177 TI - Lactose intolerance in a calf. AB - Lactose intolerance was identified as the cause of bovine neonatal diarrhea. Glucose and xylose oral absorptions were normal whereas lactose absorption was reduced relative to normal calves. Lactase deficiency is common in people but rarely reported in animals. The treatment of whole milk with lactase alleviated the diarrhea. PMID- 8455178 TI - Endemic visceral leishmaniasis in a dog from Texas. AB - Visceral leishmaniasis was diagnosed by cytology and positive indirect immunofluorescent antibody titers to Leishmania donovani in a 7-month-old female Basenji dog from Texas. Clinical and laboratory findings included weight loss, hematochezia, hyperglobulinemia, hypoalbuminemia, anemia, and neutrophilic leukocytosis. Evidence of response to treatment with diminazene aceturate and ketoconazole included improvement in the abnormal clinical, hematologic, and biochemical findings, decreased serum globulin concentration and antibody titer to Leishmania donovani, and absence of organisms in examined tissues. Several foci of endemic leishmaniasis have been reported in the United States. Because of its zoonotic potential and the lack of approved treatments for dogs with leishmaniasis in the United States, the development of effective treatment strategies is needed. PMID- 8455179 TI - Quantitative determination of equine alkaline phosphatase isoenzymes in foal and adult serum. AB - Automated and semiautomated assays were developed and validated for the determination of equine alkaline phosphatase isoenzymes including intestinal (IALP), bone (BALP), and liver (LALP). The addition of levamisole selectively inhibited more than 97% of LALP while inhibiting only 55% of IALP. Because these percentages were highly reproducible in an automated system, the IALP activity could be calculated in a sample. Bone alkaline phosphatase isoenzyme was selectively precipitated by adding an equal volume of wheat germ agglutinin (5 mg/mL), incubating for 30 minutes at 37 degrees C, and centrifugating. The LALP activity was determined from the supernatant fluid and BALP activity was calculated by subtraction from total ALP activity. The within-run coefficient of variation for determination of BALP activity was 4.7%. These assays were used to identify and quantify the isoenzymes present in pony foal sera through the first 21 days of life, in horse foal sera before colostrum ingestion and during the first 21 days of life, and in adult horse and pony sera. Intestinal ALP activity was not found in sera of any of the foals or adult ponies or horses. A majority of serum ALP activity of newborn foals is of bone origin (80 to 92%) which decreases markedly over the first 21 days. In adults, only 17.9% (51.2 +/- 18.1 U/L) of serum ALP is derived from bone. The absolute LALP activity in foal serum is similar to that in adults. PMID- 8455180 TI - Acute necrotizing pancreatitis and acute suppurative pancreatitis in the cat. A retrospective study of 40 cases (1976-1989). AB - Medical records and histologic sections of 40 cats with acute pancreatitis were reviewed. Two distinct groups of cats with pancreatitis were established by histologic analysis of tissue. Group 1 (32 cats) had acute pancreatic necrosis (APN). Group 2 (8 cats) had suppurative pancreatitis. Ages of affected cats ranged from 3 weeks to 16 years. The majority consisted of indoor cats of the Domestic Short-Haired breed but Siamese cats were over-represented relative to the general population (P < 0.05). Twenty-two percent of cats were obese and 57% were underweight. Thirty-eight percent of cats had acute disease. In the other cats, two stages in the progression of the disease were evident: (1) anorexia, weight loss, and lethargy, followed by (2) acute deterioration, development of shock, and a moribund state, despite fluid therapy. The most common clinical signs were severe lethargy (100%), reduced appetite (97%), dehydration (92%), and hypothermia (68%). The initial hemogram occasionally showed a neutrophilia (30%) and anemia (26%) but packed cell volume (PCV) decreased markedly to the extent that 55% of cats were anemic terminally. Serum biochemical abnormalities included increased activities of ALT (68%) and ALP (50%), and increased concentrations of bilirubin (64%) and cholesterol (64%). Cats with APN were hyperglycemic (64%), glycosuric (60%) and ketonuric (20%), whereas cats with suppurative pancreatitis tended to be hypoglycemic (75%). Renal failure and electrolyte abnormalities were mild or infrequent except for hypokalemia (56%). This study characterizes a severe necrotizing pancreatitis in the cat similar to that reported in other species, and a histologically distinct suppurative pancreatitis. PMID- 8455181 TI - Nocardiosis. A literature review with selected case reports in two dogs. AB - Two dogs with systemic nocardiosis are presented and the pathobiology, diagnosis, and treatment of nocardial infections are discussed. Both dogs had nonspecific respiratory signs and depression. The diagnosis was made by isolation of the organism only after surgical drainage was established and appropriate tissues were cultured. The response to surgical drainage and antimicrobial therapy was dramatic in both dogs, but one dog experienced a drug reaction to trimethoprim potentiated sulfonamide. Although systemic nocardial infections traditionally have had a grave prognosis, through early diagnosis, surgical intervention, and the use of newer, safer and synergistically acting antimicrobials, the prognosis has improved. This article reviews current human and veterinary literature regarding the microbiology, pathogenesis, and treatment of nocardiosis and reports on the successful treatment of systemic nocardiosis in two dogs. PMID- 8455182 TI - Treatment of canine nasal aspergillosis with enilconazole. AB - Twenty-four dogs with nasal aspergillosis were treated with enilconazole (10 mg/kg bid for 7-14 days) administered topically through tubes surgically implanted into the nasal chambers. Aspergillosis was eliminated in 19 dogs over a median follow-up period of 18 months. Another dog died, but at necropsy there was no evidence of causative fungus. Two of the four dogs that were not cured had infection of periorbital soft tissues. An additional seven dogs received 6 weeks ketoconazole (5 mg/kg bid PO) and enilconazole therapy topically. Six of these dogs were disease-free over a median follow-up period of 35 months. The seventh dog responded to repeated treatment with enilconazole. Twenty-six of the 29 dogs (90%) without extranasal aspergillosis were cured. PMID- 8455183 TI - Sporotrichosis. PMID- 8455184 TI - Small animal internal medicine residency. PMID- 8455185 TI - The contrasting effects of progesterone and oestrogen on the susceptibility of mice to genital infection with Mycoplasma pulmonis. AB - The genital tract of young female mice was rendered susceptible to colonisation with Mycoplasma pulmonis by pre-treating them with progesterone (usually 2.5 mg) given subcutaneously at weekly intervals for 4 weeks. Colonisation was influenced by the size of the inoculum and by the dose of progesterone; at least 2.5 x 10(4) organisms and at least 0.5 mg of hormone (administered on four occasions) were required. The duration of colonisation was related also to the size of the inoculum and the dose of progesterone. Similar results were obtained in TO, BALB/c and CBA strains of mice. Progesterone treatment induced the dioestrous stage of the reproductive cycle within 5 days and the cycle of the majority of untreated, mycoplasma-susceptible mice was also at this stage. However, mice, particularly of the CBA strain, were far less susceptible when not given progesterone and the mycoplasmas tended to persist for a shorter time. Mice treated with oestradiol, even in small doses, became completely refractory to infection with M. pulmonis. In vitro, progesterone inhibited the growth of M. pulmonis, as did oestradiol, but vaginal washings from progesterone-treated mice were no more inhibitory than those from untreated mice. Thus, the success of progesterone in enhancing colonisation could not be attributed to a direct stimulatory effect of the hormone at the mucosal surface and we suggest that it may be due to a greater availability of progesterone-induced receptors for mycoplasmas in the dioestrous phase of the reproductive cycle than in the oestrous phase. PMID- 8455186 TI - Rapid detection of Mycoplasma pneumoniae in clinical samples by the polymerase chain reaction. AB - A DNA amplification method was used to detect Mycoplasma pneumoniae in clinical samples. M. pneumoniae 16S ribosomal RNA gene sequences were selected as the amplification target region. The polymerase chain reaction (PCR) with purified DNA fragments as templates yielded an expected 88-bp fragment from M. pneumoniae but not from other Mycoplasma spp. nor from any of the other bacteria assayed. With this method, the 88-bp product specific for M. pneumoniae could be obtained from a minimum of 0.05 pg of M. pneumoniae DNA. Subsequently this PCR technique was used for the detection of M. pneumoniae in throat-swab samples. Twenty-two of 30 culture-positive clinical samples gave positive results in the PCR test. Thirty-two culture-negative clinical samples and 33 samples from healthy volunteers, of which only one was culture-positive, gave negative results in the same PCR test. This PCR method is useful for the direct detection of M. pneumoniae in clinical samples. PMID- 8455187 TI - The role of a 54-kb plasmid in the virulence of strains of Salmonella enteritidis of phage type 4 for chickens and mice. AB - The role of a 54-kb plasmid in the virulence of Salmonella Enteritidis strains of phage type 4 was examined in mice, young chickens and adult laying-hens. Although the plasmid was essential for full expression of virulence in mice, differences in expression of virulence by this 54-kb plasmid were noted among strains; thus, introduction of the plasmid to a naturally occurring strain that lacked it did not make that strain virulent. In newly hatched chickens, virulence of an Enteritidis strain of phage type 4 by oral or parenteral routes was unrelated to possession of this plasmid which, similarly, played no role in infection in egg laying hens. When a strain of Enteritidis phage type 4 and a plasmid-cured strain derived from it were given orally to chickens, both strains were equally invasive and their patterns of localisation in spleen, liver and ovaries were similar and they were isolated at similar frequencies from cultured, laid eggs. PMID- 8455188 TI - Opsonisation of group B streptococci and restriction endonuclease digestion patterns of their chromosomal DNA. AB - Isolates of group B streptococci (GBS) from neonates with early-onset septicaemia are associated with particular restriction endonuclease digestion patterns (RDP types Ia-3 and III-3) of chromosomal DNA. Opsonophagocytosis of serotype Ia and serotype III GBS isolates was studied by the luminol-enhanced phagocytic chemiluminescence (CL) assay. Pools of serum containing GBS type-specific antibody levels equivalent to or just above levels typically found in sera from mothers of infected infants were used. CL intensities induced by GBS isolates of RDP types Ia-2, Ia-3 and III-3 were lower than those of the other RDP types of the same serotype. Opsonophagocytosis was more efficient with serum containing higher concentrations of type-specific antibodies but for RDP type III-3 strains these differences were much less marked than for other RDP types. CL intensity did not correlate with cell surface charge, hydrophobicity or sialic acid content of GBS. Results demonstrate that certain GBS RDP types are more resistant to opsonophagocytosis and suggest that potentially virulent strains with genetic homogeneity may exist. PMID- 8455189 TI - Detection of penicillin tolerance in Streptococcus pyogenes. AB - Three traditional assays were used to determine the minimal bactericidal concentration (MBC) and minimal inhibitory concentration (MIC) for Streptococcus pyogenes (group A streptococci) in two phases of growth and the time taken to kill the organisms. Three other methods were used for the determination of penicillin tolerance: a cell-lysis assay, the beta-lactamase disk method and the replication method. Twenty strains, comprising penicillin-tolerant clinical isolates and two laboratory mutants, were used to evaluate the six tests. Results indicated that two groups of S. pyogenes can be distinguished--four highly tolerant and three moderately tolerant strains. The moderately tolerant strains were not recognised when rapidly growing instead of stationary cultures were used for the MBC and MIC determinations. The MBC/MIC ratio for tolerant strains was > 100. Tolerance percentage ranged from 0.30 to 1.07 and 0.29 to 3.96 for cultures in the mid-logarithmic and stationary phases of growth, respectively. The cell lysis assay, the beta-lactamase disk method and the replication method may be used to screen for tolerance. Detection of high or moderate tolerance by determining the MBC/MIC ratio for mid-logarithmic or stationary cultures is recommended. PMID- 8455190 TI - Opsonic requirements of Helicobacter pylori. AB - The opsonic requirements of Helicobacter pylori were investigated in a series of experiments with human polymorphonuclear leucocytes (PMNL). Pre-incubation of H. pylori with pooled normal human serum (NHS) in concentrations of 5-20% significantly increased the uptake of radiolabelled bacteria by PMNL. Treatment of the bacteria with NHS 30% caused the release of radiolabel and this effect was abolished by heating serum to 56 degrees C, suggesting that H. pylori is serum sensitive and that complement is involved. Opsonisation of H. pylori with NHS concentrations of 10-30% significantly increased PMNL chemiluminescence. Removal of specific antibody had no effect. Removal of either the classical or alternative complement pathways produced no significant change in PMNL chemiluminescence, indicating that either pathway is sufficient for opsonisation on its own. The results confirm that complement is the most efficient opsonin for H. pylori. PMID- 8455192 TI - Examination of archetypal strains of enteropathogenic Escherichia coli for properties associated with bacterial virulence. AB - Nine strains of Escherichia coli isolated from infants with diarrhoea between 1947 and 1960 and designated "enteropathogenic" were examined for phenotypic and genetic characters associated with virulence. Each strain belonged to a different serotype. All the isolates were historically significant in that they were amongst the first strains of E. coli reported to be causally associated with infantile diarrhoea. Five strains possessed the virulence properties of class I enteropathogenic E. coli (EPEC). All these strains were isolated originally from symptomatic children during outbreaks of diarrhoea. Two isolates from sporadic cases of diarrhoea fulfilled the criteria for classification as class II EPEC. One strain was identified as enteroaggregative E. coli and the other carried no known virulence-associated properties. These findings indicate that most early isolates of E. coli which were designated "enteropathogenic" were indeed EPEC, as currently defined. PMID- 8455191 TI - Naturally-occurring, osmo-remedial variants of Escherichia coli. AB - Two clones of Escherichia coli O27:K1:H31 and O2:H7, isolated from patients with urinary tract infection or bacteraemia, failed to grow in a synthetic minimal medium (MM) of low osmolality. They were considered to be osmo-remedial because they grew well when sufficient amounts of NaCl, mannitol or sucrose were added to raise the osmolality of the medium to > 300 mOsm/kg. The defect could also be corrected by nicotinamide or its precursors quinolinic and aspartic acids. Each clone had a unique DNA restriction enzyme profile, fimbriae and antibiotic susceptibility patterns. The osmo-remedial variants were unstable and underwent phenotypic modulation to form mixtures with osmo-tolerant forms when grown in MM. They tended to form satellites of small colonies around large colonies of osmo tolerant cells on MM agar plates. The penicillin method of Davis was used to separate the two forms. Nicotinamide induced the expression of ompF when the osmo remedial strains were grown under conditions of low osmolality. It is possible that the variants are defective in the synthesis of membrane-derived oligosaccharides or outer-membrane proteins, but this has yet to be determined. PMID- 8455193 TI - Discovering switch pharmaceuticals from multistationary biochemical networks. PMID- 8455194 TI - Congress may order breast cancer study on Long Island. PMID- 8455195 TI - Nordic countries keep employees safe from carcinogens. PMID- 8455196 TI - Perception of risk heightens stress of breast cancer screening. PMID- 8455197 TI - Freedom to puff goes up in smoke. PMID- 8455198 TI - Hydrazine sulfate ad is "offensive". PMID- 8455199 TI - Cancer in the elderly: meeting the challenge of an aging population. PMID- 8455200 TI - The kinetic properties of switch antimetabolites. AB - BACKGROUND: Maintaining homeostasis is the biological function of negative feedback, a process that plays a well-understood role in the biochemistry of antimetabolite drugs. An equally important property of living systems--the ability to respond to external stimuli by switching rapidly from one state to another--is mediated by positive feedback. Kinetic analysis of multi-enzyme biochemical pathways has shown that pathways containing positive feedback coupled with negative feedback may act as biochemical switching systems in which multiple steady states are possible. PURPOSE: A computer model was used to study the kinetic effects of antimetabolites that inhibit biochemical pathways at positive feedback sites and to determine whether the kinetics of such systems differed from those of classical antimetabolites. METHODS: Kinetics were simulated by microcomputer to model the effects of inhibitors on a simplified metabolic pathway. RESULTS: Antimetabolite drugs that act at positive feedback sites are predicted to display highly nonclassical properties. Three nonclassical properties are kinetically possible. First, the drugs may switch off the pathway at substoichiometric concentrations; classical antimetabolites require stoichiometric levels and sometimes much more. Second, instead of demonstrating classical continuous inhibition, antimetabolite drugs that act at positive feedback sites may give "all-or-none" dose-response curves with discontinuity at a specific value. Inhibitor concentrations below this value would have no overall effect on the system, while inhibitor concentrations at or above this value would give an abrupt transition to an inhibited steady state. Third, the inhibited system may show hysteresis and remain switched off after the inhibitor is removed. CONCLUSIONS: These findings suggest that antimetabolites acting at switch points could have kinetic properties very different from those of classical antimetabolites and could provide a noncytotoxic method of switching off pathways in neoplastic cells, perhaps leading to cell stasis. IMPLICATIONS: Experimental validation of these conclusions will require identification of the positive feedback sites of metabolic and signaling pathways and exploration of the effects of inhibitors of these sites. The properties of "switch antimetabolites" should prompt a search for new kinds of targets for drug design. PMID- 8455201 TI - Induction of antitumor immunity by interleukin-2 gene-transduced mouse mammary tumor cells versus transduced mammary stromal fibroblasts. AB - BACKGROUND: Tumor cell-targeted cytokine gene transfer has been used to generate tumor cell vaccines, but this approach is limited by the need to establish and implant live tumor cells. PURPOSE: The purpose of this study was to determine if stromal fibroblasts could be used as an alternative vehicle for delivery of the cytokine interleukin-2 (IL-2) into the tumor microenvironment. We attempted to establish the feasibility of (a) genetic immunotherapy in a mammary tumor system and (b) engineering stromal fibroblasts as well as tumor cells. We compared the effects of tumor cell-mediated and stromal fibroblast-mediated local IL-2 expression on the generation of antitumor immune responses. METHODS: Retroviral vectors containing a human IL-2 gene were used to transduce a mouse mammary tumor line, 4TO7, and an immortalized but nontumorigenic fibroblast line established from syngeneic mammary fatpads. Expression of the IL-2 gene in transduced cells was determined by measuring IL-2 secretion, by RNA-polymerase chain reaction, and by immunochemistry. Groups of 5-12 BALB/c mice were injected with either 4TO7 cells or various doses of IL-2-secreting 4TO7 cells (4TO7-IL-2); tumor growth was monitored. To test whether local IL-2 expression by transduced cells could influence the growth of unmodified tumor cells, we determined tumor development in groups of mice treated with 4TO7 cells co-injected with either 4TO7-IL-2 cells or IL-2-secreting fibroblasts. RESULTS: 4TO7-IL-2 cells induced active immunity able to reject the immunizing tumor and to resist challenge with parental 4TO7 cells on the contralateral side. Mice pretreated with 4TO7-IL-2 were significantly protected compared with untreated control animals or mice pretreated with irradiated 4TO7 cells. The immunity induced by 4TO7-IL-2 cells did not protect against challenge with another subline, 4T1, which was derived from the same spontaneously arising mammary tumor as 4TO7. Co-injection of 4TO7 cells with 4TO7-IL-2 cells reduced tumorigenicity, whereas co-injection of 4TO7 cells with IL-2 secreting fibroblasts did not. CONCLUSION: Our results suggest that induction of anti-tumor immune response by local IL-2 production is most effective when the helper cytokine is secreted by the tumor cell. IMPLICATION: Our studies caution against the use of IL-2 gene-transduced syngeneic stromal cells as an alternative strategy of gene therapy for cancer. However, they may allow study of the mechanisms of tumor antigen recognition and the possible involvement of co-stimulatory signals for effective tumor vaccination by gene modified cells. PMID- 8455202 TI - Report of the Cancer Therapy Evaluation Program monitoring plan for secondary acute myeloid leukemia following treatment with epipodophyllotoxins. AB - BACKGROUND: Recent reports have documented the occurrence of treatment-related acute myeloid leukemia (AML) following therapy with epipodophyllotoxins. These reports have led to growing concern among oncologists, which could lead to premature abandonment of these agents at a time when the relationship between cumulative dose of epipodophyllotoxin and risk of treatment-related AML has not been determined. PURPOSE: Because of the increasingly important role of epipodophyllotoxins in the treatment of several types of adult and pediatric tumors, the Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI) has developed a monitoring plan to obtain reliable estimates of the risk of treatment-related AML following epipodophyllotoxin treatment. METHODS: We identified 12 NCI-supported Cooperative Group clinical trials in which patients with solid tumors are being treated with epipodophyllotoxins at different cumulative doses. One trial is using a moderate dose of teniposide (900 mg/m2), and 11 trials are using etoposide at a low dose (< 1500 mg/m2), a moderate dose (1500-3999 mg/m2), or a high dose (> or = 4000 mg/m2). Cases of treatment-related AML and treatment-related myelodysplastic syndrome (MDS) (hereafter referred to as treatment-related AML/MDS) occurring in these trials are reported to CTEP, with initial analysis for each cumulative dose group triggered by the reporting of four cases of treatment-related AML/MDS in that group. For each analysis, total patient follow-up for the group is determined and cumulative 6-year incidence rate is calculated. RESULTS: Three cases of treatment related AML and one case of treatment-related MDS (with documented monosomy 7) were reported in a group of 207 patients who received etoposide at a low cumulative dose. The calculated 6-year rate of development of treatment-related AML/MDS was 3.2% (95% upper confidence interval bounded by 7.2%). CONCLUSIONS: The 6-year cumulative rate of treatment-related AML/MDS (3.2%) is within the range previously reported for alkylator-based regimens that did not include epipodophyllotoxins. IMPLICATIONS: Previous reports have suggested that higher cumulative doses of alkylators are associated with increased risk of treatment related AML, and a critical goal of the monitoring plan is to determine whether a similar relationship exists for the epipodophyllotoxins. Estimates will be developed for leukemogenic risk for the moderate- and high-cumulative-dose groups when four cases of treatment-related AML/MDS have been identified within each group. PMID- 8455203 TI - Concordance of self-reported data and medical record audit for six cancer screening procedures. AB - BACKGROUND: Self-reported data about the interval since last cancer screening are often used to determine whether individuals are due for periodic screening and to monitor adherence to guidelines for early cancer detection. PURPOSE: In a study conducted within the Kaiser Permanente Medical Care Program, we examined the concordance of self-reported information and medical record documentation about recency of and reasons for six procedures for early cancer detection. We also assessed the concordance of population-level estimates of screening rates based on these two sources. METHODS: Data were obtained from a mailed questionnaire or telephone interview completed by 779 men and women. The data from these randomly selected study participants (431 women and 348 men), who had been members of the health plan for the previous 5 years, were compared with information obtained from their medical charts. Intersource agreement about whether each procedure was done within the last 2 years was evaluated, with the medical record used as the gold standard. To assess the accuracy of patient self-reporting, we also calculated sensitivity, false-positive and false-negative results, and Kappa statistics. RESULTS: Concordance between self-reported data and medical record documentation was greater for procedures that generated a test report (mammogram, Pap smear, fecal occult blood test, and sigmoidoscopy) than for those generating a physician's note (clinical breast examination and digital rectal examination). Kappa statistics showed a similar pattern. Sensitivity of self-reported data was more than 90% for mammogram, clinical breast examination, Pap smear, and fecal occult blood test and nearly 80% for sigmoidoscopy and digital rectal examination. However, false-positive results were above 40%, except for fecal occult blood test and sigmoidoscopy. For all six procedures, estimated population level rates of screening within the past 2 years would have been significantly higher (P < .0001) if self-reported data were used instead of medical record audit data. CONCLUSIONS: Self-reported data may overestimate the percentage of the population that has been screened and underestimate the interval since the last cancer detection procedures. IMPLICATIONS: Such data should be used cautiously for clinical decision making, research, and surveillance activities at both individual and population levels. Also, comparability of data should be considered when population screening rates are evaluated on the basis of different data sources. PMID- 8455204 TI - Heat shock protein hsp70 in patients with axillary lymph node-negative breast cancer: prognostic implications. AB - BACKGROUND: Cell synthesis of heat shock (stress-response) proteins is increased by a variety of environmental and pathophysiological stressful conditions. The 70 kd heat shock protein (hsp70) is thought to be involved in protein-protein interactions including those of the protein products of the human c-myc oncogene and the p53 (also known as TP53) tumor suppressor gene. PURPOSE: The purpose of this study was to investigate whether elevated hsp70 expression may be an indicator of biological stress experienced by a breast cancer and may, therefore, predict disease outcome. METHODS: Levels of hsp70 were determined by Western blot analysis in primary breast tumors from patients with negative axillary lymph nodes. We performed exploratory data analyses on a set of 162 primary breast cancers and constructed prognostic indexes of hsp70 expression levels. The optimal cutpoint for hsp70 expression was considered to be the value yielding the greatest separation for disease-free survival for the resulting two groups of patients. That cutpoint was then validated in a set of 345 tumors by univariate and multivariate analyses. Data were analyzed for overall survival, disease-free survival, tumor size, and patient age, as well as estrogen receptor and progesterone receptor status, ploidy (DNA content), and percentage of cells in S phase as determined by flow cytometry. RESULTS: Expression of hsp70 emerged as a useful prognostic factor, both in univariate and in multivariate analyses. Patients whose tumors had high expression of hsp70 had significantly shorter disease-free survival (P = .006). The other statistically significant factors were S-phase fraction (P = .008) and tumor size (P = .01). For patients who received adjuvant therapy, hsp70 was the only independent predictor of disease recurrence (P = .05). For those with tumors 1-3 cm in diameter, hsp70 (P = .008) and S-phase fraction (P = .02) were statistically significant predictors of recurrence. CONCLUSIONS: Measurement of hsp70 expression in primary tumors from patients with node-negative breast cancer may be useful in identifying patients at high risk for disease recurrence and thus may affect decisions regarding treatment after surgery. IMPLICATIONS: Future studies should be performed to determine if detection of hsp70 by immunohistochemistry can be used to predict clinical outcome and to better understand the relationships between hsp70 and the effects of various treatment modalities. PMID- 8455205 TI - Nonsteroidal anti-inflammatory drugs in skin cancer: revisited. PMID- 8455206 TI - Severe interaction between methotrexate and a macrolide-like antibiotic. PMID- 8455207 TI - Astrogliosis in culture: I. The model and the effect of antisense oligonucleotides on glial fibrillary acidic protein synthesis. AB - Astrogliosis is a predictable response of astrocytes to various types of injury caused by physical, chemical, and pathological trauma. It is characterized by hyperplasia, hypertrophy, and an increase in immunodetectable glial fibrillary acidic protein (GFAP). As GFAP accumulation is one of the prominent features of astrogliosis, inhibition or delay in GFAP synthesis in damaged and reactive astrocytes might affect astrogliosis and delay scar formation. The aim of this study is to investigate the possibility of utilizing antisense oligonucleotides in controlling the response of astrocytes after mechanically induced injury. We scratched primary astrocyte cultures prepared from newborn rat cerebral cortex with a plastic pipette tip as an injury model and studied the astrogliotic responses in culture. Injured astrocytes became hyperplastic, hypertrophic, and had an increased GFAP content. These observations demonstrate that injured astrocytes in culture are capable of becoming reactive and exhibit gliotic behaviors in culture without neurons. The increase in GFAP content in injured astrocytes could be inhibited by incubating the scratched culture with commercially available liposome complexed with 3' or 5' antisense oligonucleotides (20 nt) in the coding region of mouse GFAP. The scratch model provides a simple system to examine in more detail the mechanisms involved in triggering glial reactivity and many of the cellular dynamics associated with scar formation. Antisense oligonucleotide treatment could inhibit the GFAP synthesis in injured astrocytes, hence it may be applicable in modifying scar formation in CNS injury in vivo. PMID- 8455208 TI - Molecular analysis of the nerve growth factor inducible ornithine decarboxylase gene in PC12 cells. AB - In an effort to understand molecular mechanisms by which nerve growth factor (NGF) regulates gene expression, we have isolated a full-length rat cDNA clone encoding ornithine decarboxylase (ODC) and utilized this probe to identify and examine the transcriptionally active, NGF inducible ODC gene in rat PC12 cells. This same gene is also responsive to epidermal growth factor, basic fibroblasts growth factor, and dibutyryl cAMP. Primer extension analysis demonstrates that both basal and NGF induced transcription of the ODC gene utilize the same major transcriptional start site, demonstrating that NGF acts to increase transcriptional activity at the basal start site as opposed to unmasking an alternative, stronger start site. Functional promoter analysis reveals the presence of a constitutive core promoter residing between positions -201 and +390, relative to the start site of transcription. Additional analyses reveal that sequences in the region -7800 to +2257 are insufficient to mediate NGF induced transcriptional activation, demonstrating that at least some of the regulatory sequences necessary for NGF mediated transcriptional induction of the ODC gene must reside at relatively enormous distances from the transcriptional start site. Such a long distance transcriptional regulatory mechanism is unique when compared with other NGF responsive genes that have been similarly analyzed. PMID- 8455209 TI - Regulation of phospholipase D activity in a human oligodendroglioma cell line (HOG). AB - Oligodendroglial cells express many specific proteins, such as myelin basic protein (MBP), which are physiologically phosphorylated by protein kinase C (PKC). Diacylglycerols are physiological activators of PKC and can be liberated from phospholipids by the direct receptor-mediated activation of phospholipase C (PL-C) or indirectly via the activation of phospholipase D (PL-D). In a well characterized human oligodendroglioma (HOG) cell line, PL-C (measured by release of [3H]inositol phosphates) and PL-D (formation of [3H]myristoylated or palmitoylated phosphatidylethanol) were activated by both carbachol (blocked by pirenzepine, suggesting an M1 receptor) and histamine (H1 receptor) but not glutamate, bradykinin, or phenylephrine. PL-C stimulation by carbachol or histamine was completely inhibited by short-term treatment (< 30 min) with phorbol ester (TPA), a PKC activator. In contrast, PL-D activation by either carbachol or histamine was stimulated in additive fashion by TPA, suggesting at least two distinct mechanisms for PL-D activation. Down regulation of PKC by prolonged (24 hr) treatment with TPA reversed the inhibitory effects of TPA on PL C and the stimulatory effects on PL-D. However, the PKC inhibitors H-7 and galactosylsphingosine did not inhibit the TPA-mediated stimulation of PLD while the less-specific PKC inhibitor, staurosporine, was only partially inhibitory. Preexposure of cells to carbachol, greatly reduced both PL-C and PL-D activation by carbachol, suggesting homologous desensitization. Time-course studies indicated that PL-D activation (10 sec or less) was at least as fast as PL-C activation, and the affinity of carbachol and histamine for the receptor coupled to either phospholipase (EC50 = 5-10 microM) was about the same.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455210 TI - Plasminogen activator inhibitor 1, the primary regulator of fibrinolysis, in normal human cerebrospinal fluid. AB - The occurrence of type-1 plasminogen activator inhibitor (PAI-1) in human cerebrospinal fluid (CSF) has not previously been reported. As a member of the serpin superfamily of serine protease inhibitors and an acute phase response component, PAI-1 has powerful potential roles in nervous system homeostasis. We have detected this serpin antigen using a polyclonal anti-PAI-1 antibody in normal human CSF. In Western blotting, PAI-1 in several CSF samples appears as a two-band antigen of Mr = 54 and 35 kDa, presumably the intact and proteolytic fragment, respectively. In vitro complex formation studies confirm that the 54 kDa form of PAI-1 interacts with 125I-urokinase after activation with SDS, but the 35 kDa form does not. Quantification of total PAI-1 antigen in 18 normal human CSF samples by ELISA reveals a mean value of 1.0 +/- 0.07 (SEM) micrograms/dL, indicating that a relatively low concentration of the inhibitor occurs in normal human CSF. This information should now allow comparison of PAI-1 levels and activity in various neurologic disorders. PMID- 8455211 TI - Selective modulation of cholinergic properties in cultures of avian embryonic sympathetic ganglia. AB - We have studied the expression of catecholaminergic and cholinergic phenotypes in sympathetic ganglia removed from 7- to 10-day-old quail embryos and grown in vitro under different conditions. Quantitative data were obtained by measuring the conversion of (3H) tyrosine and (3H) choline to catecholamines (CA) and acetylcholine (ACh), respectively. In explant cultures, large amounts of both neurotransmitters were synthesized from the onset, but CA generally predominated, the molar ratios of CA:ACh being, on average, of the order of 2:1. If the ganglia were dissociated before plating, there was a selective increase in ACh synthesis (three- to fivefold) such that the CA:ACh ratio fell strikingly. The early expression of the cholinergic phenotype appears to be species-specific in that, under identical conditions, dissociated cell cultures of newborn mouse superior cervical ganglia were overwhelmingly catecholaminergic (CA:ACh ratio of approximately 40:1) and ACh synthesis was only just detectable. Addition of veratridine (1.5 microM) either to explant or to dissociated cell cultures of embryonic quail sympathetic ganglia barely altered CA-synthesizing ability; in contrast, ACh synthesis and accumulation were stimulated about threefold. This effect, which we found to correspond to a quantitatively similar increase in the activity of choline acetyltransferase (ChAT), was completely blocked by tetrodotoxin, indicating that it was due to Na(+)-dependent depolarization. A preferential stimulation of ACh production was also observed when the concentration of K+ was raised to 20 mM. Veratridine treatment of cultures of presumptive sympathoblasts, in the form of sclerotome-associated neural crest cells, had identical effects. Our results reveal the quantitative importance of ACh-related properties in avian sympathetic ganglia from the earliest stages of their development and suggest that depolarization may be one of the factors selectively enhancing expression of the cholinergic phenotype during ontogeny. In these respects, the neurochemical differentiation of sympathetic neurons unfolds according to dissimilar scenarios in birds and mammals. PMID- 8455212 TI - Application of synthetic phospho- and unphospho- peptides to identify phosphorylation sites in a subregion of the tau molecule, which is modified in Alzheimer's disease. AB - Phospho- and unphospho- peptides were used to define the essential sequence for a tau epitope, which is recognized by Tau-1 antibody and phosphorylated in Alzheimer's disease (AD). The epitope was mapped within the amino acid residues 192-199 of tau and was phosphorylated by the p34cdc2/p58cyclin A proline directed kinase (PDPK), but not by purified mitogen activated protein kinase (p42mapk). Addition of phosphate to the last serine of the epitope was the most effective in abolishing the reactivity of the epitope to Tau-1 antibody. Our results suggest that one and possibly more members of the PDPK family may play a role in the pathogenesis of AD. PMID- 8455213 TI - New concepts in dysphagia management. AB - This review presents an outline of the new and expanding role of otolaryngologists in the management of swallowing disorders. It emphasizes an holistic approach to swallowing management. Better understanding of swallowing analysis and the unglamorous yet essential role of conservative management will lead to improvements in surgical treatment and overall patient care. PMID- 8455214 TI - Ultrasonic opportunities. 1992 William J. Fry Memorial Lecture. PMID- 8455215 TI - Frequency of fetal anomalies in sonographically detected polyhydramnios. AB - One hundred and five patients who met the criterion of having an amniotic fluid pocket depth greater than 8.0 cm were categorized as polyhydramniotic. Of these cases, 82% were singleton pregnancies and 18% were twin pregnancies. The degree of polyhydramnios correlated directly with the probability that an anomaly would be detected. For the lowest rank group (pocket depth of 8 to 9.5 cm), 50% of fetuses manifested an anomaly, whereas the highest rank (16.0 cm or greater pocket depth) carried an 88% risk for an anomaly. Overall, 63% of pregnancies with polyhydramnios revealed anomalies. Sonography found all to be anomalous. There were three false diagnoses of potential anomalies. Monochorionic anomalies of twinning (twin transfusion syndrome and acardiac twin) and gastrointestinal anomalies among singletons were the most commonly seen abnormalities. However, a broad spectrum of anomalies was represented in the study group. Only five diabetic mothers were seen in our study cohort, and in each of them the pregnancy was further complicated by an associated fetal anomaly. PMID- 8455216 TI - Noninvasive assessment of pressure gradients across iliac artery stenoses: duplex and catheter correlative study. AB - The present study investigates prospectively the validity and accuracy of the simplified Bernoulli equation in the duplex-derived determination of pressure gradients across iliac artery stenoses in patients with occlusive artery disease. In 28 patients (age range, 38 to 76 years; mean, 53 years) with short iliac artery stenoses, we obtained both duplex scan stenotic jet velocity and catheter pressure measurements. Mean and maximum pressure gradients were determined by both methods, as was the peak-to-peak catheter gradient. The correlation between the duplex-determined and nonsimultaneously measured catheter mean pressure gradients was r = 0.77 (standard error of the estimate [SEE] = 5 mm Hg), that between the duplex-derived and catheter-determined maximum pressure gradients was r = 0.80 (SEE = 10 mm Hg), and that between maximum duplex-determined and peak-to peak catheter gradient was r = 0.76 (SEE = 12 mm Hg). The peak-to-peak catheter gradient was significantly lower than the maximum duplex-derived gradient (46 versus 53 mm Hg, P < 0.05). Duplex-determined mean pressure gradient decreased from 15 +/- 6 to 3 +/- 1 mm Hg after balloon angioplasty of the iliac stenoses. Duplex scan can be used to predict pressure gradients across short iliac artery stenoses, provided that errors caused by angle malcompensation are prevented. PMID- 8455217 TI - The role of sonographically guided aspiration in the clinical management of ovarian cysts. AB - This study was undertaken to verify the role of fine-needle aspiration (FNA) followed by cytologic examination as a possible alternative to surgery in case of cystic pelvic masses. From January 1988 to March 1989, 204 patients with a proven cystic pelvic mass underwent FNA under sonographic guidance. In 20 cases the aspiration was performed transvaginally. Thirty-six patients were postmenopausal. In all cases the aspirated fluid was collected for cytologic evaluation. Other than one case of persistent hematuria, no complications occurred. The overall recurrence rate, verified 3 months from FNA, was 65%. Fifty-two per cent of patients developed a new cyst after a complete aspiration. Fifty-three patients underwent a laparotomy, allowing a comparison between cytologic and histologic patterns. The sensitivity of cytologic examination of aspirated fluids was 40% (3 of 5 malignancies were missed) and the specificity was 100% (no false positives were observed). We conclude that FNA might be proposed in young women with a unilocular ovarian cyst to avoid a surgical procedure. In postmenopausal women with a unilocular cystic mass 5 cm or less, FNA may be considered as an important step in the diagnosis. In all instances the ultrasonographic appearance of the cyst (echo texture and regularity of wall) and the characteristics of aspirated fluid are the most important findings. When the aspirated fluid contains mucus or blood, or when a complex mass is present, exploratory laparotomy or a laparoscopy is recommended. PMID- 8455218 TI - Sonographic subchorial hypoechoic areas are found frequently and in most cases have no influence on fetal outcome. PMID- 8455220 TI - Color Doppler sonography of ovarian masses: a multiparameter analysis. AB - This study analyzed vessel location, maximum systolic velocity, impedance, and waveform shape in 25 benign and 25 malignant surgically excised and pathologically examined ovarian masses as depicted by transvaginal or transabdominal color Doppler sonography, or both. Those parameters that achieved statistical significance (P > 0.05) between the two types of masses included vessel location, impedance, and waveform shape. Malignant masses typically were characterized by centrally located vessels that had low impedance without a diastolic "notch" in the waveform. Maximum systolic velocities are statistically similar in benign and malignant lesions. Multiparameter analysis may improve the diagnostic specificity and sensitivity of this technique in distinguishing benign from malignant ovarian masses. PMID- 8455219 TI - Is avoidance of surgery possible in patients with perimenopausal ovarian tumors using transvaginal ultrasound and duplex color Doppler sonography? AB - A total of 108 cases of small perimenopausal ovarian tumors (largest diameter, less than 7 cm) were evaluated by transvaginal sonography and duplex color Doppler sonography; 101 had criteria for benignity and 7 for malignancy. All cysts were punctured and aspirated to avoid unnecessary surgery (benign cases) and establish the cytologic diagnosis as well as to avoid the risk of leakage (malignant cases). Recurrence rate of benign punctured cysts was 25% within 1 year of follow up. No difference in recurrent rate was seen between pre- and postmenopausal patients (19 of 56 cases in the premenopausal group, and five of 28 cases in the postmenopausal group). The larger the cyst, the greater the risk of recurrence. Puncture and aspiration of seven sonographically established malignant tumors allowed cytologic diagnosis before surgery, and no evidence of leakage was noted at the time of surgery. No significant differences were observed between cytologic and histopathologic findings in cases that went to surgery. Puncture and aspiration of small endometriomas (17 cases) was found to be inefficient for therapeutic purposes. Finally, owing to the high percentage of unsatisfactory cytologic results (20%) with cyst aspiration, vaginal and color Doppler sonography seemed more efficient in distinguishing between benignity and malignancy. PMID- 8455221 TI - Sonographically guided laparoscopy and mediastinoscopy using miniature catheter based transducers. AB - Miniature ultrasound transducers (12.5 MHz) housed in 9 Fr catheters were passed through a laparoscope or mediastinoscope to image a variety of normal and abnormal structures within the peritoneal cavity and mediastinum in 20 patients. These transducers made it possible to visualize the gallbladder and bile ducts and evaluate for the presence of stones, to detect masses and provide guidance for their aspiration or biopsy, and to image the internal structures of the ovary and fallopian tube. In addition, these miniature transducers were used to locate such normal vital structures as blood vessels, thereby allowing the surgeon to decide on the best approach for dissection during mediastinoscopy. During conventional surgery, the surgeon or gynecologist can palpate an area of abnormality not directly visualized. However, during laparoscopy and mediastinoscopy direct palpation is not possible. Therefore, it is important to find another method to determine what structures lie beneath the visualized surface. These miniature ultrasound transducers appear to offer a means for making such determinations. PMID- 8455222 TI - Calcified inferior vena cava thrombus in a fetus: perinatal imaging. PMID- 8455223 TI - Primary cervical choriocarcinoma: case report and review of the literature. PMID- 8455224 TI - Ectopic gestation associated with intrauterine triplet pregnancy after in vitro fertilization. PMID- 8455225 TI - Antenatal diagnosis and subsequent management of hydronephrosis. PMID- 8455226 TI - Percutaneous resection of renal cysts: a long-term followup. AB - Renal cysts are incidentally seen in ultrasonographic studies and are usually asymptomatic. However, some patients still present with symptoms due to a renal cyst. Various techniques have been reported for the treatment of renal cysts. Percutaneous resection of symptomatic cysts has been performed at our hospital since 1984. We investigated the long-term results of 10 patients who underwent percutaneous resection of renal cysts after a median followup of 45.7 months regarding the recurrence rate, late sequelae and clinical efficiency. Successful resection with no evidence of renal cysts was obtained in 50% of the patients at followup, a recurrence in 30% and residual cysts with up to a 45% decrease in size in 20%. All patients were cured of the symptoms and none had any late complications. We believe that percutaneous resection of renal cysts represents a valuable technique for the treatment of patients with symptomatic renal cysts. Neither postoperative nor late complications occurred after a median followup of 45.7 months. PMID- 8455227 TI - Improved success of living unrelated renal transplantation with cyclosporine immunosuppression. AB - Kidney transplantation with a living unrelated donor was performed in 13 patients. The donors comprised 10 spouses, 2 brothers-in-law and 1 stranger. All donor-recipient pairs were red blood cell compatible with a negative T cell crossmatch. Five patients underwent transplantation before 1984 without cyclosporine immunosuppression; the 1-year patient and graft survival rates in this group were 40% and 20%, respectively. Eight patients have undergone transplantation since 1985 with cyclosporine immunosuppression. The 1-year patient and graft survival rates in this group were 100% and 88%, respectively (p = 0.03). Currently, 6 patients in the latter group have a well functioning graft with serum creatinine levels of 1.2 to 2.0 mg./dl. (mean 1.5 mg./dl.) and with followup of 1 to 6 years (mean 2.9 years). Excellent graft survival results can now be achieved with living unrelated donors and their expanded use can provide an important additional source of organs for transplantation. PMID- 8455228 TI - Vesicoureteral reflux and lower urinary tract injury: the possible role of suprapubic cystostomy. AB - Incidental vesicoureteral reflux was noted frequently during routine cystographic evaluation of patients who suffered vesicourethral trauma and who were managed by suprapubic cystostomy. Based on this observation we designed a retrospective study to document the prevalence of vesicoureteral reflux among 30 consecutive patients following vesicourethral trauma. In 9 patients drainage was instituted by urethral catheter and in 21 by suprapubic cystostomy. Of the latter 21 patients 10 (47.6%) had evidence of vesicoureteral reflux on cystography, which was associated with complete rupture of the urethra in 9 (90%). No patient who was treated initially with a urethral catheter had evidence of vesicoureteral reflux on cystography. We conclude that the prevalence of vesicoureteral reflux is significantly affected by the coexistence of severe vesicourethral injury and the presence of suprapubic cystostomy. The significance of this observation is in the potential risk of ascending upper urinary tract infections due to the hazardous combination of vesicoureteral reflux and frequent recurrent lower urinary tract infections. Presence of vesicoureteral reflux in these patients may necessitate a prophylactic antibiotic regimen. The specific mechanisms that lead to increased prevalence of vesicoureteral reflux in patients following severe vesicourethral injury are not defined by our results. However, we propose a multifactorial concept that may explain our observation. PMID- 8455229 TI - The bladder mucus (glycosaminoglycan) layer in interstitial cystitis. AB - The thin mucus or glycosaminoglycan layer of the bladder may be implicated in the pathogenesis of interstitial cystitis. We developed a specific anti-mucus, antisera stabilization technique to study the ultrastructural morphological appearance of the layer, and have used this technique to compare the surface morphology of 10 control and 10 interstitial cystitis patients. The electron micrographs demonstrate the ultrastructural characteristics of the pathological changes seen in interstitial cystitis but they did not show any significant difference in the morphological appearance of the mucus or glycosaminoglycan layer between the 2 groups. PMID- 8455230 TI - Treatment of cyclophosphamide-induced hemorrhagic cystitis with intravesical carboprost tromethamine. AB - We review our experience with 18 consecutive patients who received intravesical carboprost tromethamine, an F2-alpha prostaglandin, for severe hemorrhagic cystitis following cyclophosphamide chemotherapy. Of the patients 16 were given cyclophosphamide for conditioning before bone marrow transplantation and 2 received the drug as cytotoxic therapy alone (dose range 3.6 to 15.8 gm.). All patients had severe gross hematuria that was refractory to forced diuresis and to continuous saline bladder irrigation. The intravesical prostaglandin therapy was initiated only after significant transfusion requirements (greater than 1 unit packed red blood cells per day) and/or numerous catheter manipulations for relief of clot retention. Eligible patients underwent complete clot evacuation followed by intravesical instillation of 0.4 to 1.0 mg.% carboprost tromethamine for 2 hours 4 times per day, alternating with continuous saline bladder irrigation for 2 hours. Six patients attempted an alternate protocol of 0.8 to 1.0 mg.% carboprost tromethamine given by continuous saline bladder irrigation. Complete resolution of gross hematuria occurred in 9 patients (50%). Eight patients had a partial response, with decreased transfusion requirements noted. However, complete resolution ultimately required an alternative therapy (for example formalin or urinary diversion). One patient (6%) failed to respond and required formalin therapy on day 4 of carboprost tromethamine therapy. Decreased red blood cell transfusion requirements were noted during and after therapy when compared to pretreatment values. No changes in renal or bladder function were noted during the mean followup of 17 weeks (range 1 to 64 weeks). There were 3 cases of recurrent hematuria. Side effects were limited to bladder spasm in 14 of the 18 patients (78%), with no systemic complications. The results suggest that carboprost tromethamine is a useful bedside therapy for hemorrhagic cystitis due to cyclophosphamide, and treatment appears to have minimal toxicity. PMID- 8455231 TI - Transvaginal repair of enterocele. AB - The urologist actively involved in the treatment of female genitourinary disease must to be able to recognize and treat various forms of pelvic prolapse. Enterocele is commonly seen in conjunction with stress urinary incontinence and cystocele or it may result from surgery to correct these problems. Many techniques to correct enterocele have been developed, including transvaginal repairs as well as intra-abdominal procedures such as the Moschcowitz technique or colpofixation to the sacrum for enterocele with vault prolapse. Surgical management of enterocele must take into account several factors, including the presence of stress urinary incontinence, rectocele, vaginal vault prolapse, prior hysterectomy and the desire to maintain sexual activity. Based on these considerations we discuss our approach to the transvaginal repair of enterocele. In patients without vault prolapse a simple enterocele repair is performed. If vault prolapse is present, then the condition of the anterior vaginal wall is considered. In patients with a cystocele a vault suspension procedure is performed, which involves simultaneous suspension of the uterosacral-cardinal ligament complex and vaginal vault along with the bladder neck and bladder. There are 2 modifications of this technique depending on the degree of cystocele: the 4 corner vault suspension for grades 2 and 3 cystocele, and the vault suspension with grade 4 cystocele repair. Patients with vault prolapse and no cystocele undergo sacrospinous ligament fixation. In elderly patients who are not sexually active, especially if they are in poor medical condition, partial colpocleisis is considered. In these patients partial colpocleisis was not performed as a primary procedure but it was done later in 3 who failed an initial attempt at repair. All coexisting vaginal pathology is fixed at the time of enterocele repair. A total of 83 patients underwent enterocele repair according to this protocol and 81 were available for followup. Mean followup was 15 months (range 3 to 70). Overall a successful result (no recurrence) was achieved in 70 patients (86%). Success for individual procedures was 40 of 49 (82%) for simple repair, 24 of 25 (96%) for vault suspension and 6 of 7 (86%) for sacrospinous fixation. In all cases vault suspension or sacrospinous fixation was able to restore vaginal depth and axis with minimal or no vaginal shortening. PMID- 8455232 TI - Long-term results of antral gastrocystoplasty. AB - Long-term results of gastrocystoplasty had not been reported in the literature. The results of 10 patients (7 augmentation and 3 replacement) during 15 years were reviewed. All patients voided spontaneously and achieved daytime continence. Enuresis occurred in 3 patients. Median peak flow rate and post-void residual urine were 16.0 ml. per second and 10 ml., respectively. Average cystometric capacity was 554 ml. and median pressure at full capacity was 46 cm. water. Phasic contractions resulted in pressures higher than 50 cm. water in 4 patients. Small capacity, absence of bladder sensation and high pressure were identified as risk factors for a poor result. Routine urine culture was positive in 20.5%. Urine mucus content remained low. Electrolyte disturbance, histopathological abnormalities and ulcer syndrome related to hypergastrinemia were absent. The data showed that antral gastrocystoplasty is superior because of the low infective complication rate, ability to empty and absence of metabolic disturbance. PMID- 8455233 TI - Results of 4 years of experience with bladder replacement using an ileocecal segment with multiple transverse teniamyotomies. AB - Since 1987, 30 patients with bladder cancer underwent cystoprostatectomy with bladder replacement via ileocecourethrostomy. Multiple transverse teniamyotomies were made in the cecum to assure a large capacity reservoir with low pressures. The particular anatomy and physiology of the cecum, short length of the intestinal segment needed and teniamyotomies are the 3 factors that have allowed for good functional and metabolic results. All patients achieved daytime continence. After 3 years of followup 67% of the patients were continent at night if they voided every 3 or 4 hours and 22% if they voided every 2 or 3 hours, while 11% experienced enuresis. Urodynamic data after 1 year showed a mean capacity of 396 ml. for the new bladder, a mean full filling pressure of 28 cm. water and a mean maximum pressure of 55 cm. water. Post-micturition residual urine volume was consistently less than 55 ml. These results indicate that the ileocecal segment can be enlarged with myotomies through the tenia to produce an adequate capacity and a low pressure bladder replacement without the need for formal detubularization. PMID- 8455234 TI - Prognostic significance of bromodeoxyuridine high labeled bladder cancer measured by flow cytometry: does flow cytometric determination predict the prognosis of patients with transitional cell carcinoma of the bladder. AB - We studied whether flow cytometric determination of proliferative cell activity estimated by the bromodeoxyuridine in vitro labeling technique provides significant prognosticators beyond the classical histological evaluation in the patient with bladder cancer. We evaluated 81 patients with transitional cell carcinoma of the bladder using fresh bladder specimens. Clinical followup of at least more than 24 months was requested, with the mean followup being 37.9 +/- 10.5 months. Tumor grade and stage were the histological prognostic parameters. Flow cytometric bivariate measurements of deoxyribonucleic acid (DNA) ploidy and bromodeoxyuridine labeled cell index were evaluated. Tumors with a bromodeoxyuridine labeled cell index of more than 10.7%, which was the value of the mean plus 2 times the standard deviation obtained in grade 1 bladder tumors, were designated as high bromodeoxyuridine labeled cell index tumors. A total of 51 patients with low bromodeoxyuridine labeled cell index tumors demonstrated a 98.0% 3-year actuarial survival rate estimated by the Kaplan-Meier method, compared to 42.9% for those with high index tumors. Multivariate survival analysis was performed with Cox's proportional regression model to study statistical individual prognostic values of histological and flow cytometric parameters. Histological tumor grade was the single most important prognostic factor (risk ratio 13.2, p < 0.05), with tumor stage being the second most important (risk ratio 9.2, p < 0.05), followed by bromodeoxyuridine labeled cell index status (risk ratio 6.9, p < 0.05). DNA ploidy status did not influence the clinical outcome. When grade 3 tumors were classified as low and/or high bromodeoxyuridine labeled cell index tumors, 3-year actuarial survival rates were 85.7% and 27.3%, respectively. These results indicate that DNA/bromodeoxyuridine bivariate analysis can be used as an effective adjunct to histological examination for prognostication and decision-making in treatment of bladder cancer patients. PMID- 8455235 TI - Intravesical bacillus Calmette-Guerin immunoprophylaxis of superficial bladder cancer: results of a controlled prospective trial with modified treatment schedule. AB - A controlled prospective trial on 94 patients evaluated the efficacy of intravesical Pasteur strain bacillus Calmette-Guerin (BCG) administration as prophylaxis against tumor recurrences after complete endoscopic resection of superficial bladder cancer. The treatment schedule, consisting of an initial 6 week course of instillations and a single quarterly maintenance dose to the responders, was modified to those of the latter who were at high risk for recurrence and who received an additional separate 4-week course of therapy. The percentage of the patients treated prophylactically with BCG and who remained free of recurrences (68%, mean followup 33.8 months) was significantly higher than that of the controls who underwent transurethral resection only (41%, mean followup 30.2 months). In terms of relative risk of recurrences, recurrence rate per 100 patient-months and disease-free interval, comparisons between the 2 groups of patients revealed a significant benefit for the BCG group overall as for those subjects having stages Ta and T1 tumors, multifocal tumors, a history of disease, and grades 2 and 3 carcinoma. Drug-induced toxicity was acceptable. Our study suggests that our modified treatment protocol is notably safe and effective against recurrent superficial bladder cancer. PMID- 8455236 TI - A prospective European Organization for Research and Treatment of Cancer Genitourinary Group randomized trial comparing transurethral resection followed by a single intravesical instillation of epirubicin or water in single stage Ta, T1 papillary carcinoma of the bladder. AB - A total of 431 eligible patients with solitary, primary or recurrent stages Ta and T1 transitional cell carcinoma of the bladder was included in a randomized multicenter trial to compare a single intravesical instillation of 80 mg. epirubicin with water given immediately after resection, with respect to the disease-free interval and recurrence rate. The interval to initial recurrence was significantly better in favor of the epirubicin group. After a mean followup of 2 years it became evident that the recurrence rate after a single epirubicin instillation was decreased by nearly half with the same trend being found in all subgroups examined. Toxicity was mainly restricted to bladder irritation in plus or minus 10% of the cases. Pathology review brought considerable changes in T category from stages T1 to Ta (53%). Changes in grade were less pronounced but nevertheless important. PMID- 8455237 TI - Methotrexate, vinblastine, doxorubicin and cisplatin followed by radiotherapy or surgery for muscle invasive bladder cancer: the University of Chicago experience. AB - A total of 29 patients with muscle invasive bladder cancer, clinical stage T2N0 (12), T3aN0 (9), T3bN0 (5), T3N2 (2) or T4N2 (1), underwent 2 to 4 cycles of neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) chemotherapy followed by either radiotherapy (15), radical cystectomy (11) or no local therapy (3). The overall response rate to M-VAC chemotherapy was 69%, with 31% clinical complete responses and 38% clinical partial responses. A functioning bladder was maintained in 55% of the responding patients, although bladder wall calcifications were observed in 4 of 15 irradiated patients. Overall survival was 71% and disease-free survival was 55% at a median followup of 57 months. For the 12 stage T2N0 cancer patients overall survival was 100% at a median followup of 52 months. For the stages T3a and T3bN0 cancer patients overall survival was 63%, while all 3 node positive patients died. Neoadjuvant chemotherapy with a modified M-VAC regimen is well tolerated and may result in bladder preservation. PMID- 8455238 TI - The rationale for en bloc pelvic lymph node dissection for bladder cancer patients with nodal metastases: long-term results. AB - From August 1971 through June 1989, 591 consecutive patients underwent curative pelvic lymphadenectomy with en bloc radical cystectomy for bladder cancer. Of these patients 132 (22%) had pathologically proved nodal metastases. The incidence of positive nodes increased with increasing pathological stage of the primary tumor: stage PIS (0.75%), stage P1 (13%), stage P2 (20%), stage P3a (24%), stage P3b (42%) and stage P4 (45%). The median followup for the 31 patients still alive was 5.5 years (range 2.6 to 18.8). Recurrent bladder cancer was documented in 89 patients (67%) with a median interval to progression of 1.5 years. Pelvic recurrence as the first site of progression was uncommon, occurring in 15 patients (11%). The actuarial 2, 3, 5 and 10-year survival rates were 55%, 38%, 29% and 20%, respectively. Increased risk of progression and death was associated with advanced pathological tumor stage (stage P3b or greater, p < 0.001 and p < 0.001, respectively) and 6 or more positive nodes (p < 0.001 and p = 0.012, respectively). There was no significant difference in survival and interval to progression among patients who received preoperative irradiation or adjuvant chemotherapy compared to those treated with surgery alone. This retrospective analysis further substantiates the philosophy that single stage pelvic lymphadenectomy with en bloc radical cystectomy can provide long-term progression-free survival, particularly for patients with localized primary tumors and minimal metastatic nodal disease. PMID- 8455239 TI - Posterior urethral obliteration treated by endoscopic reconstitution, internal urethrotomy and temporary self-dilation. AB - Five patients with complete posterior urethral obliteration (less than 3 cm.) underwent endoscopic reconstitution of the urethra followed by planned direct vision internal urethrotomy and temporary self-dilation. Of these patients 3 complied with the treatment regimen and are currently free of voiding complaints (average followup 31 months), while 2 failed to perform self-dilation and required repeat internal urethrotomy. Of the latter 2 patients 1 then performed self-dilation and has a stable urethra (followup 2 years). The youngest patient refused to perform self-dilation and underwent successful perineal urethroplasty. Major complications did not occur. The treatment regimen as described is a suitable alternative to surgical urethroplasty in select patients with short urethral defects (less than 3 cm.) who are willing to perform temporary urethral self-dilation. PMID- 8455240 TI - Relationship between varicocele size and response to varicocelectomy. AB - We studied the relationship between varicocele size and response to surgery in 86 men with a unilateral left varicocele who reported either infertility (83), pain (1) or pain and testicular atrophy (2). Varicoceles were graded according to size: grade 1--small (22 patients), grade 2--medium (44) and grade 3--large (20). Sperm count, per cent motility, per cent tapered forms and fertility index (sperm count times per cent motility) were measured preoperatively and postoperatively. Preoperatively, men with grade 3 varicocele had lower sperm counts and poorer fertility indexes compared to men with grades 1 and 2 varicocele. Sperm concentration improved significantly in men with grade 2 (33 +/- 5 million per cc preoperatively to 41 +/- 6 million postoperatively, p < 0.04) and grade 3 (18 +/- 5 million preoperatively to 32 +/- 7 million postoperatively) varicocele after microsurgical ligation of the varicocele. Motility improved significantly in men with grade 3 varicocele. Decrease in per cent tapered forms was significant in all groups. A comparison of per cent change in fertility index among the groups revealed that men with grade 3 varicocele improved to a greater degree (128%) than men with grade 1 (27%) or grade 2 (21%) varicocele. Pregnancy rates 2 years postoperatively were 40% for grade 1, 46% for grade 2 and 37% for grade 3 varicocele patients. The difference in pregnancy rates among the groups was not statistically significant. In conclusion, infertile men with a large varicocele have poorer preoperative semen quality but repair of the large varicocele in those men results in greater improvement than repair of a small or medium sized varicocele. PMID- 8455241 TI - Inverted V peritoneotomy significantly improves nodal yield in laparoscopic pelvic lymphadenectomy. AB - We compared the nodal yield and volume of target tissue removed in 3 groups of patients undergoing laparoscopic pelvic lymphadenectomy as a staging procedure for carcinoma of the prostate. With the exception of the type of peritoneotomy used to expose the obturator fossa, surgical management of all patients was identical. Results were evaluated in patients undergoing linear peritoneotomy (40), inverted V peritoneotomy (14) or both procedures (28, 1 approach on each side). Significantly more tissue was removed from patients in the inverted V group (16.3 +/- 8.3 cm.3) compared to the linear peritoneotomy group (7.2 +/- 5.7 cm.3, p = 0.004). This resulted in a significant increase in nodal yield in patients in the inverted V group (11.0 +/- 4.1) relative to the linear peritoneotomy group (6.8 +/- 5.2, p = 0.003). In terms of the volume of tissue removed and the number of nodes obtained, combination patients had values intermediate to those in the other groups (11.6 +/- 10.5 cm.3 and 8.8 +/- 5.6 nodes, respectively). The right-to-left ratio of nodes and tissue volume was reversed in the combination group relative to the other 2 groups. Operative time was significantly decreased for the inverted V technique compared to the linear peritoneotomy approach (p = 0.01). No difference in operative blood loss of complications was identified. The improved exposure obtained with this technique appears to result in a more complete lymphadenectomy without increased risk of complications. PMID- 8455242 TI - Invasion of Denonvilliers' fascia in radical prostatectomy specimens. AB - Denonvilliers' fascia consists of a single fibromuscular structure covering the posterior aspect of the prostate and surrounding the seminal vesicles. This structure has multiple layers that are fused together, and to the stroma of the prostate and seminal vesicles. A separate posterior layer of Denonvilliers' fascia was not seen during radical prostatectomy. The cleavable interprostatorectal plane extends posteriorly throughout the thickness of Denonvilliers' fascia and anteriorly to the muscular wall of the rectum. Medially this fascia is fused with the prostatic capsule into a single sheath and contains thick smooth muscle bundles in continuity with the prostatic stroma. In a series of 243 radical prostatectomy specimens for prostate cancer, we studied the morphological relationship of Denonvilliers' fascia with the prostatic capsule and stroma, and traced the progression of prostatic cancer in relation to the anatomical landmarks. In 19% of the cases tumor was found progressing within Denonvilliers' fascia, in the medial posterior area of the prostate, unrelated to perineural space invasion. For specimens with an intracapsular cancer volume of less than 12 cc, which may be cured by radical prostatectomy alone, the frequency of invasion of Denonvilliers' fascia was 13%. In these cases cephalad progression of cancer was seen almost exclusively in Denonvilliers' fascia overlying the central zone at the prostate base and surrounding the seminal vesicles. Invasion of Denonvilliers' fascia can lead to positive surgical margins if complete excision of this fascia is not performed during radical prostatectomy. Even among large tumors in our series there were no cases of tumor invasion completely through the full thickness of Denonvilliers' fascia at the posterior medial area and, therefore, rectal wall invasion was never suspected at this level. PMID- 8455243 TI - Control of the deep dorsal venous complex in radical retropubic prostatectomy. AB - We describe a method to control the deep dorsal venous complex, which has allowed for a considerable decrease in blood loss during radical retropubic prostatectomy. We reviewed 28 consecutive patients treated with this technique with respect to blood loss (982 ml.), operating room time (197 minutes), complications, postoperative hospitalization and transfusion requirements. The results are favorable when compared to previous reports. PMID- 8455244 TI - The Raz bladder neck suspension in patients 65 years old and older. AB - We reviewed the charts of 92 women 65 years old and older (mean age 72 years, range 65 to 87 years) who underwent the Raz bladder neck suspension between January 1984 and June 1990 for stress urinary incontinence. Mean followup was 17 months. Overall, a successful outcome (cure or rare stress urinary incontinence not requiring protection) was achieved in 81 patients (88%). The 2-sample Wilcoxon rank sum test showed that the only predictor of outcome was the subjective degree of preoperative stress urinary incontinence (mild, moderate or severe, p = 0.0148). When the results were stratified by degree of incontinence preoperatively 8 of 8 patients (100%) with mild, 62 of 67 (93%) with moderate and 11 of 17 (65%) with severe incontinence had a successful outcome. Prior hysterectomy, number and type of previous anti-incontinence procedures, and the presence of urgency, urgency incontinence or urodynamic instability were not statistically significant predictors of outcome. In addition, the degree of clinical instability preoperatively had no correlation with the degree of postoperative instability. Of 11 failures 10 occurred within 1 year postoperatively. Significant urgency incontinence was present preoperatively in 32% of the patients with postoperative resolution in 60%. De novo urgency and urgency incontinence occurred in 24% and 13% of the patients, respectively. There was no statistically significant difference in the outcome of surgery in patients 65 years old and older compared to 141 patients less than 65 years old with respect to success, cure of stress urinary incontinence, cure of significant urgency and urgency incontinence, and appearance of de novo instability. The Raz bladder neck suspension is a safe and efficacious treatment for stress incontinence in elderly women. Outcomes can be expected to be the same as in younger women. PMID- 8455245 TI - Experience with duplex system anomalies detected by prenatal ultrasonography. AB - We reviewed 39 neonates with prenatally diagnosed duplex system anomalies. Principal diagnoses were ureterocele in 15 patients, ureteral ectopia in 15, lower polar vesicoureteral reflux in 6, lower pole ureteropelvic junction stasis in 2 and yo-yo reflux in an incompletely duplicated system in 1. Several patients had other ipsilateral and contralateral urinary anomalies. Ten patients (26%) had relevant physical signs and only 1 became symptomatic, with urosepsis, neonatally. At initial assessment, before any accounted urinary tract infection, renal polar function as judged by radionuclide examinations almost always was severely impaired in the presence of major ureteral ectopia or severe reflux. By contrast, function was usually well preserved when there was obstruction, or lesser degrees of ectopia or reflux. A total of 19 patients underwent surgery (14 electively and 5 after episodes of urosepsis), while 20 have been managed nonoperatively for 12 to 84 months (mean 34) during which time the appearances and function of the upper renal tracts have remained stable. We conclude that the natural history of these anomalies is often benign and that a policy of routine surgical intervention, developed when most cases presented symptomatically, may not be appropriate in patients who present antenatally. PMID- 8455246 TI - Ureterocystoplasty: a unique method for vesical augmentation in children. AB - Vesical augmentation may be accomplished by using small bowel, large bowel or stomach, and by detrusor myotomy or the autoaugmentation technique. The use of intestinal segments is associated with variable mucus production, electrolyte absorption and the risk of malignant transformation. Autoaugmentation is free of these potential risks but may be unsuccessful in creating sufficient improvement in vesical compliance and capacity. Ureterocystoplasty with a bladder based native ureteral flap has been used in neurovesical dysfunction in association with a nonfunctional refluxing kidney, in a noncompliant valve bladder associated with posterior urethral valves and a nonfunctional kidney, and in augmentation of a small bladder after closure of cloacal exstrophy. Adequate bladder capacity and compliance have been achieved without the use of extra urinary epithelium. The surgical approach is simple and uncomplicated. Ureterocystoplasty in selected cases will provide for adequate bladder capacity and compliance when augmentation cystoplasty is required. PMID- 8455247 TI - Modified longitudinal preputial island flap urethroplasty for repair of hypospadias: results in 60 patients. AB - We report the results of hypospadias repair in 60 children requiring urethral reconstruction using a longitudinal or oblique preputial island flap technique that includes the inner and outer surfaces of the prepuce to construct the neourethra. Mean patient age was 3.2 years and mean length of the repair was 3.1 cm. The cosmetic and functional results were satisfactory. The incidence of urethrocutaneous fistula was 8.3% and that of meatal stenosis was 5%. Thus, this modification offers good results with a low complication rate. The range of applications can be extended by combining the technique with a tube of midline scrotal skin in cases of scrotal or perineal hypospadias. The surgical technique is described in detail. PMID- 8455248 TI - Paragonimus calcified ova mimicking left renal staghorn stone. AB - We report on a 49-year-old woman with clusters of Paragonimus calcified ova unusually located in the left retroperitoneal space and renal capsule mimicking a left renal staghorn stone. The diagnosis and treatment are discussed. We also reviewed the endemic condition of paragonimiasis in Taiwan. PMID- 8455249 TI - Metastatic renal cell carcinoma presenting as impotence. AB - We describe a patient who initially presented with impotence followed by progressive lethargy and visual disturbances. Endocrine and radiological evaluation was suggestive of pituitary adenoma but pathological evaluation after transsphenoidal hypophysectomy revealed renal cell carcinoma metastatic to the pituitary. The etiology of this unusual presentation and prior reports of renal cell carcinoma spread to the pituitary are reviewed. PMID- 8455250 TI - A case of a compound heterozygote for adenine phosphoribosyltransferase deficiency (APRT*J/APRT*Q0) leading to 2,8-dihydroxyadenine urolithiasis: review of the reported cases with 2,8-dihydroxyadenine stones in Japan. AB - We report a case of a compound heterozygote for adenine phosphoribosyltransferase deficiency (APRT*J/APRT*Q0) leading to 2,8-dihydroxyadenine urolithiasis. Polymerase chain reaction-single strand conformation polymorphism analysis demonstrated that APRT*J and APRT*Q0 alleles from the father and mother, respectively, had been transmitted to the patient. We also reviewed the literature regarding Japanese patients with 2,8-dihydroxyadenine urolithiasis. There seemed to be little difference in clinical course between type 2 homozygotes and compound heterozygotes. However, hemolysate APRT activities of compound heterozygotes were lower than those of type 2 homozygotes. PMID- 8455251 TI - Laparoscopic treatment of ureteral obstruction secondary to ovarian remnant syndrome. AB - A case is presented in which an ovarian remnant following total abdominal hysterectomy and bilateral salpingo-oophorectomy resulted in unilateral ureteral obstruction. The obstructing tissue was excised laparoscopically with simultaneous ureteroscopic monitoring. PMID- 8455252 TI - Computerized tomography in the diagnosis of appendicovesical fistula. AB - Appendicitis and its complications are among the causes of an enterovesical fistula, with approximately 100 such cases reported. This condition is seldom diagnosed preoperatively and surgery is often delayed. We report 2 cases of an appendicovesical fistula that were diagnosed preoperatively by computerized tomography (CT). We describe a CT finding consistent with the diagnosis, namely calcification in the thickened bladder wall adjacent to the cecum on noncontrast CT, which is a fecalith in the lumen of the fistula. PMID- 8455253 TI - Conservative treatment of a vesicocervical fistula resulting from Shirodkar cervical cerclage. AB - A case of a vesicocervical fistula caused by Shirodkar cervical cerclage and presenting as total urinary incontinence is reported. The patient was managed conservatively by bladder drainage alone with complete resolution of the fistulous tract. This rare complication is avoidable if the bladder is adequately dissected from the cervix during placement of the cerclage suture. PMID- 8455254 TI - Acute hemorrhagic cystitis caused by adenovirus following renal transplantation: review of the literature. AB - We report on 4 male patients with acute hemorrhagic cystitis caused by adenovirus following renal transplantation. These patients showed symptoms of gross hematuria, urinary frequency, burning urination and fever. Adenovirus was isolated in all patients and 3 were positive for serotype 11. Complement-fixing antibody was positive for adenovirus in all cases. Acute hemorrhagic cystitis caused by adenovirus was self-limiting and reduction of immunosuppression was not required for its resolution. Clinical presentation of these patients is described and the literature is reviewed. PMID- 8455255 TI - Lymphoepithelioma of the bladder: a clinicopathological study of 3 cases. AB - Lymphoepithelioma of the bladder is rare and has only recently been described at this site. Based upon the reported sensitivity to chemotherapy of lymphoepitheliomas at more common sites, we treated 3 cases of muscle invasive lymphoepithelioma of the bladder with primary chemotherapy to salvage bladder function. PMID- 8455256 TI - Aortic occlusion and lower extremity exercise induced stress urinary incontinence. AB - An unusual case of intermittent stress urinary incontinence associated with lower extremity exercise in a patient with aortoiliac occlusive disease is reported. Preoperative noninvasive vascular testing revealed severe compromise of lower extremity and pelvic blood flow. Fluoroscopically guided preoperative urodynamic evaluation without exercise revealed a competent urethral sphincter mechanism that became incompetent following exercise sufficient to induce claudication. The claudication and exercise-induced incontinence resolved after aortobifemoral bypass, and postoperative urodynamic studies were normal. PMID- 8455257 TI - Histoplasmosis of the penis. AB - Histoplasmosis is a common cause of systemic mycosis in endemic areas of the United States. Genitourinary and cutaneous involvement with this dimorphous fungus is rare. We report a case of disseminated histoplasmosis associated with nonpainful ulcerative lesions of the glans and shaft of the penis. PMID- 8455258 TI - The native venous architecture is preserved in an arterialized deep dorsal vein graft for arteriogenic impotence: a case report. AB - Endothelial injury in a deep dorsal vein graft may result from thermal, ischemic or mechanical trauma during surgical preparation or following exposure to systemic blood pressures and flow. We removed a functioning in situ deep dorsal vein graft section 10 months after microvascular arterial bypass surgery due to glans hyperemia. This section was compared and contrasted histomorphologically with a preoperative deep dorsal vein section that was procured for routine histological examination before the arteriovenous anastomosis. Detailed examination of the vein graft tissues by light microscopy, computer morphometrics and immunological staining demonstrated no evidence of vascular pathology. In the normal, healthy deep dorsal vein graft exposure to systemic arterial blood pressures and flow for 10 months did not result in myointimal proliferative lesions. Such histological changes seem more likely to be attributable to endothelial injury following iatrogenic surgical trauma. In situ vein grafts offer the opportunity to use "no-touch" endothelium preserving vascular techniques. Use of these grafts may improve long-term clinical results in penile microvascular arterial bypass surgery for impotence as it has in other vascular beds. PMID- 8455259 TI - Multilocular prostatic cystadenoma presenting as a large complex pelvic cystic mass. AB - Symptomatic prostatic cysts are not common. We report a case of a large complex cystic pelvic mass encountered in a Jordanian man that proved to be a huge midline prostatic cyst with seminal vesicle contained within the wall. This finding represents a variation of the newly proposed diagnosis, multilocular prostatic cystadenoma. PMID- 8455260 TI - Re: Transmembrane oxalate exchange and its relationship to idiopathic calcium oxalate nephrolithiasis. PMID- 8455261 TI - Air embolism during kidney transplantation. PMID- 8455262 TI - Re: Pararectus retroperitoneal radical nephrectomy. PMID- 8455263 TI - Re: A comparison of the urological complications associated with long-term management of quadriplegics with and without chronic indwelling urinary catheters. PMID- 8455264 TI - Re: Development of the human anterior urethra. PMID- 8455265 TI - Misdiagnosis of sexual abuse. PMID- 8455266 TI - Re: Corporeal plication for surgical correction of Peyronie's disease. PMID- 8455267 TI - Re: Endoscopic release of retained Penrose drains: a simple solution for an old problem. PMID- 8455268 TI - The renal hemodynamic response to endothelin in chronic cyclosporine-treated dogs. AB - Use of the immunosuppressive agent cyclosporine A (CyA) is limited by its associated nephrotoxicity, characterized by an increase in renal vascular resistance (RVR) and reductions in renal blood flow (RBF) and glomerular filtration rate (GFR). The vascular endothelium produces vasoactive substances including endothelium derived relaxation factor (EDRF) and endothelin (ET), which modulate vascular tone. Since CyA has been shown to damage the endothelium, we examined the renal hemodynamic response to intrarenal ET infusion (4 micrograms./kg./minute) in chronic cyclosporine-treated dogs. Prior to ET infusion, CyA-treated dogs had a lower RBF and a greater RVR than normal dogs. In normal dogs, after ET infusion RVR increased from 30.24 +/- 0.64 to 44.60 +/- 1.66 mmHg./ml./minute (p < 0.001), RBF decreased from 4.26 +/- 0.28 to 2.90 +/- 0.30 ml./min./g. (p < 0.001) and GFR decreased from 50.20 +/- 5.90 to 36.50 +/- 7.90 ml. per minute (p < 0.001). In contrast, there was no change in RBF, GFR and RVR after intrarenal ET infusion in CyA-treated dogs. Prior to ET infusion, arterial plasma ET concentration was 5.0 +/- 1.1 pg./ml. in CyA-treated dogs, similar to 7.5 +/- 1.4 pg./ml. in normal dogs, and was not significantly altered in either group after intrarenal ET infusion. We conclude that ET may not contribute to the increased RVR in chronic cyclosporine nephrotoxicity, and suggest a vascular toxicity of CyA, rendering renal vessels unresponsive to the vasoconstrictive effect of ET. PMID- 8455269 TI - Impaired bladder perfusion in interstitial cystitis: a study of blood supply using laser Doppler flowmetry. AB - Laser doppler flowmetry was used to study bladder blood flow in 16 patients with interstitial cystitis and in 18 control subjects. All studies were performed at cystoscopy under general anesthesia. Interstitial cystitis patients conformed to the diagnostic criteria of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Blood flow measurements were made at four specific sites in the bladder at a capacity of 100 ml. and at full capacity. The mean maximum capacity under anesthesia was 828 cc for the control group and 562 cc for the IC group. Blood flow at low capacity was similar in the two groups. When the bladder was filled to capacity, blood flow increased by a mean of 9.05 LDF units in the control group but only by 0.06 LDF units in the IC group (p = 0.007). Vault perfusion increased considerably more in the control group compared to the IC group (p = 0.002). The mean ratio of vault to trigonal perfusion was similar in both groups and was not affected by the overall blood flow changes which accompanied distension. Although the mean bladder capacity under anesthesia was greater in the control group, covariant analysis showed that the significant differences in perfusion between the two groups occurred independently of changes in capacity. It is concluded that bladder perfusion at capacity is significantly impaired in interstitial cystitis. PMID- 8455270 TI - An ultrastructural study of experimentally induced microliths in rat proximal and distal tubules. AB - Calcium oxalate stone formation was induced in rats by oral application of ethylene glycol and ammonium chloride for 4, 8 and 24 days. After each induction period, light-microscopically, birefringent crystals were seen in the tubular lumen and, intracellularly, in proximal and distal tubular cells. After a postfixation which partially removed the crystalline material crystal ghosts were seen by electron microscopy. In the lumen, crystal ghosts were observed ranging from single crystals to crystal agglomerates. The large intraluminal agglomerates were surrounded by epithelial cells and cellular debris. Both crystal types had an organic interior. In the cytoplasm of ultrastructurally changed proximal tubular cells, small (200 to 600 nm. in diameter) single crystal ghosts were present in the terminal web at the basis of the microvilli. Others were present in large vacuolar structures, with a fine granular matrix. After the prolonged microlith induction periods, such vacuolar structures were seen throughout the cell. The organic matrix of the crystal ghosts therein had acquired a more aggregated and complex structure. PMID- 8455271 TI - Electron energy-loss spectroscopical and image analysis of experimentally induced rat microliths. II. AB - Following a microlith-inducing diet of ethylene glycol plus ammonium chloride, intraluminal and intracellular crystals are observed in aldehyde-fixed rat proximal and distal tubule cells by light and electron microscopy. Qualitative, in-situ analysis with electron-probe X-ray microanalysis (EPMA) of these intraluminal and intracellular crystals shows the presence of calcium, a trace of magnesium, some chlorine and the virtual absence of phosphorus and sulphur. Electron energy-loss spectroscopical element (EELS) analysis and electron spectroscopic imaging (ESI) confirm, at both sites, the presence of calcium. Selected area electron diffraction (a) confirmed the crystallinity of both the intracellular and intraluminal crystals; (b) produced identical diffractograms from intracellular crystals in proximal tubule cells and deliberately internalized exogenous COM-crystals in cultured LLC-PK1 cells and (c) produced mean dhkl-values, identical to the dhkl-values from calcium oxalate monohydrate (14-771) in the ASTM index, from 4 different intracellular crystals in proximal tubule cells. PMID- 8455272 TI - Prepubertal vasal injury: its effect on postpubertal vas deferens. AB - At this institution, via clinical observation at laparoscopy, a phenomenon was noted in humans that was associated with injury to the prepubertal vas deferens. There were 4 cases that presented with apparent atrophy of the abdominal pelvic portion of the vas deferens following injury to the vas in the prepubertal period. A study was undertaken to see if this phenomenon could be duplicated in an animal model. Prepubertal Sprague-Dawley rats were selected and divided into several groups ranging from sham surgery to unilateral partial vasectomy. These groups allowed for observations following different modes of trauma as well as creation of a control population. Additionally, an adult group was studied to evaluate the effects of vas injury in the adult rat. In the adult group, following trauma to the vas, no changes in the abdominal pelvic portion of the vas were noted. In the prepubertal group, with ligation and with segmental excision (partial vasectomy), striking diminution in outer diameter and wall thickness of the distal vas deferens was noted. This study indicates that the rat prepubertal vas serves as a good model for study of the human vas deferens. Further studies are underway which seek to elicit the mechanism of the observed injury. PMID- 8455273 TI - Hemodynamics of pelvic nerve induced erection in a canine model. II. Cavernosal inflow and occlusion. AB - Using a previously developed canine model of erection, we measured pudendal artery and venous flow as well as pressure in the corpora cavernosa, pudendal artery and vein. Penile erection was induced by pelvic nerve stimulation. Generalized arterial vasodilatation was dependent on stimulation frequency and occurred most prominently at stimulation frequencies of approximately 16 Hz. Cavernosal smooth muscle relaxation was also frequency dependent in a similar manner. In contrast, using a technique of delayed arterial inflow, we demonstrated that helicine artery relaxation was very sensitive to stimulation frequency and occurred only at a stimulation frequency of approximately 16 Hz. The mechanism of corporal occlusion is primarily dependent on nerve-induced relaxation of the cavernosal smooth muscle. The frequency-dependent nature of pelvic nerve induced erection is primarily due to the frequency dependence of the cavernosal resistance vessels that control arterial inflow to the cavernosal spaces. PMID- 8455274 TI - Pharmacological manipulation of acute cyclosporin ischemic renal injury with trimetazidine. AB - Cyclosporin has had a major impact on organ transplantation, but associated nephrotoxicity is a significant problem. Renal hypothermia, a known anti-ischemic maneuver, limits cyclosporin-ischemic renal failure. Pharmacological manipulation with an anti-ischemic agent, such as trimetazidine, may prevent cyclosporin nephrotoxicity. We tested this hypothesis in a canine single kidney model of cyclosporin-enhanced ischemic renal failure. Trimetazidine treatment was associated with significantly better biochemical and histological markers of renal function and structure. Trimetazidine may have a role to play in protecting against cyclosporin nephrotoxicity in clinical renal transplantation. PMID- 8455275 TI - Origin of neurons supplying the vas deferens of the rat. AB - Retrograde axonal tracing methods using Fluoro-Gold were used to examine the neuronal input to the vas deferens in the adult Wistar rat. The greatest number of labelled efferent neurons were found in the ipsilateral pelvic accessory ganglion (PAG) (68%) and the major pelvic ganglion (MPG) (15%). Fewer than 3% of labelled neurons were localized to the inferior mesenteric and sympathetic chain ganglia. Labelled neurons were also located in the ipsilateral L1, L2, and L6, S1 dorsal root ganglia (DRG), corresponding to afferents that travel in the hypogastric and pelvic nerves, respectively. Contributions from contralateral neurons in the PAG, MPG and L1 DRG were also documented. The role of afferents supplying the vas deferens is not known but they may relay nociceptive or mechanoreceptive input. Efferent input from peripheral ganglia probably contributes to contractility of the vas deferens based on previous investigations. PMID- 8455276 TI - Congenital immunodeficiencies in mice increase susceptibility to urinary tract infection. AB - Severe combined immunodeficient (SCID), T cell deficient, and immunocompetent mice were challenged intravesically with viable uropathogenic Escherichia coli. In comparison to immunocompetent controls, SCID mice had significantly greater numbers of viable E. coli in their bladders and kidneys 7 days after inoculation. Splenic anti-E. coli antibody-forming cells (AFC) were virtually absent in SCID mice at 7.0 days after infection. Adoptive transfer of spleen cells from E. coli immunized immunocompetent mice to SCID mice enhanced their resistance to urinary tract infection (UTI), as evidenced by lower bacterial counts in bladder and kidneys following an induced infection. Congenitally T cell deficient nude mice and immunocompetent heterozygous controls had equivalent bladder and kidney infection levels at 2 and 7 days after UTI. Immunocompetency thus appears to play a significant role in resistance to E. coli UTI in this animal model. Since mice deficient only in T cells did not show increased UTI susceptibility, T cell independent antibody responses may be an important immunologic defense mechanism. PMID- 8455277 TI - Toradol, an NSAID used for renal colic, decreases renal perfusion and ureteral pressure in a canine model of unilateral ureteral obstruction. AB - Toradol is a new parenteral, nonsteroidal anti-inflammatory drug which is efficacious in treating renal coli. In the present experiments, Toradol was administered to both control dogs and dogs with unilateral ureteral obstruction. In control dogs, Toradol had no effect on RBF or GFR, despite inhibition of renal prostaglandin synthesis (measured as urinary prostaglandin release). In contrast, RBF fell acutely by 35% (p < 0.001) within 15 minutes of Toradol administration in the setting of ureteral obstruction; contralateral RBF was unaffected. Ipsilateral ureteral pressure also fell. Changes in RBF and ureteral pressure, together with the known effects of NSAIDs on pain pathways, may contribute to the pain relief observed clinically with Toradol. However, the abrupt changes in renal hemodynamics brought on by Toradol to the obstructed kidney may compromise renal reserve, and Toradol should be used cautiously in treating renal colic. PMID- 8455278 TI - The natural history of renal lesions in von Hippel-Lindau disease: a serial CT study in 28 patients. PMID- 8455279 TI - Hispanic/Latino health issues explored. PMID- 8455280 TI - Rural reformers eye 'managed cooperation'. PMID- 8455281 TI - Satellite hookup links major US military hospital with Army physicians in Mogadishu, Somalia. PMID- 8455282 TI - Thanks to gift from Ross Perot, University of Texas Southwestern's MD-PhD Program triples in size. PMID- 8455283 TI - Statisticians offer overall incidence estimates for various kinds of cancer during this year. PMID- 8455284 TI - From the National Institutes of Health. PMID- 8455286 TI - From the Centers for Disease Control and Prevention. Infant mortality--United States, 1990. PMID- 8455285 TI - From the Centers for Disease Control and Prevention. State activities for prevention of lead poisoning among children--United States, 1992. PMID- 8455287 TI - Physicians and outpatients diagnostic imaging: overexposed? PMID- 8455288 TI - Physicians and outpatients diagnostic imaging: overexposed? PMID- 8455289 TI - Unrecognized false-positive ketones from drugs containing free-sulfhydryl group(s) PMID- 8455290 TI - Clinical ecology. PMID- 8455291 TI - Treating cancer with coffee enemas and diet. PMID- 8455292 TI - AIDS and priorities in the global village. PMID- 8455293 TI - Dr Doctor calls back. PMID- 8455294 TI - Dr Doctor calls back. PMID- 8455296 TI - US intern plus dictionary becomes Russian doctor. PMID- 8455295 TI - Effects of beer on breast-fed infants. PMID- 8455297 TI - Declining blood lead levels and cognitive changes in moderately lead-poisoned children. AB - OBJECTIVE: To determine whether chelation therapy or biochemical changes during a lead-lowering intervention was associated with changes in cognitive functioning of moderately lead-poisoned children. It was hypothesized that cognitive performance would improve as blood lead level declined over time. DESIGN: Short term intervention study with measures obtained before and after intervention. SETTING: Hospital specialty clinic and university research center. PATIENTS: A total of 154 previously untreated children referred to clinic with blood lead levels between 1.21 and 2.66 mumol/L (25 and 55 micrograms/dL) at time of enrollment. Ages ranged from 13 to 87 months. INTERVENTION: Enrolled children were treated with edetate calcium disodium (EDTA) if eligible and/or with orally administered iron supplement if iron deficient. For all children, housing inspections and abatement procedures were performed as necessary. MAIN OUTCOME MEASURES: Score on Bayley Mental Development Scale or Stanford-Binet Intelligence Scale (4th edition). RESULTS: There was no effect of edetate calcium disodium treatment per se. In the short term (7 weeks), changes in blood lead levels were not related to changes in cognitive scores. In the long term (6 months), however, changes in performance were significantly related to changes in blood lead level, even after controlling for confounding variables. The standardized score increased 1 point for every decrease of 0.14 mumol/L (3 micrograms/dL) in blood lead level. CONCLUSION: The results suggest an association between decreases in blood lead level and cognitive improvements in moderately lead-poisoned children. PMID- 8455298 TI - Lead-contaminated soil abatement and urban children's blood lead levels. AB - OBJECTIVE: To test the hypothesis that a reduction of 1000 ppm or more of lead in soil accessible to children would result in a decrease of at least 0.14 mumol/L (3 micrograms/dL) in blood lead levels. SETTING: Urban neighborhoods with a high incidence of childhood lead poisoning and high soil lead levels. DESIGN: Randomized controlled trial of the effects of lead-contaminated soil abatement on blood lead levels of children followed up for approximately 1 year after the intervention. PATIENTS: A total of 152 children less than 4 years of age with venous blood lead levels of 0.34 to 1.16 mumol/L (7 to 24 micrograms/dL). Children were largely poor and had a mean age at baseline of 32 months, a mean blood lead level of 0.60 mumol/L (12.5 micrograms/dL), and a median surface soil lead level of 2075 ppm. INTERVENTIONS: Children were randomized to one of three groups: the study group, whose homes received soil and interior dust abatement and loose paint removal; comparison group A, whose homes received interior dust abatement and loose paint removal; and comparison group B, whose homes received only interior loose paint removal. MAIN OUTCOME MEASURES: Change in children's blood lead levels from preabatement levels to levels approximately 6 and 11 months after abatement. RESULTS: The mean decline in blood lead level between preabatement and 11 months after abatement was 0.12 mumol/L (2.44 micrograms/dL) in the study group (P = .001), 0.04 mumol/L (0.91 microgram/dL) in group A (P = .04), and 0.02 mumol/L (0.52 microgram/mL) in group B (P = .31). The mean blood lead level of the study group declined 0.07 mumol/L (1.53 micrograms/dL) more than that of group A (95% confidence interval [CI], -0.14 to -0.01 mumol/L [-2.87 to -0.19 micrograms/dL]) and 0.09 mumol/L (1.92 micrograms/dL) more than group B (95% CI, -0.16 to -0.03 mumol/L [-3.28 to -0.56 micrograms/dL]). When adjusted for preabatement lead level, the 11-month mean blood lead level was 0.06 mumol/L (1.28 micrograms/dL) lower in the study group as compared with group A (P = .02) and 0.07 mumol/L (1.49 micrograms/dL) lower than in group B (P = .01). The magnitude of the decline independently associated with soil abatement ranged from 0.04 to 0.08 mumol/L (0.8 to 1.6 micrograms/dL) when the impact of potential confounders, such as water, dust, and paint lead levels, children's mouthing behaviors, and other characteristics, was controlled for. CONCLUSIONS: These results demonstrate that lead-contaminated soil contributes to the lead burden of urban children and that abatement of lead-contaminated soil around homes results in a modest decline in blood lead levels. The magnitude of reduction in blood lead level observed, however, suggests that lead-contaminated soil abatement is not likely to be a useful clinical intervention for the majority of urban children in the United States with low-level lead exposure. PMID- 8455299 TI - Use of coronary artery bypass surgery in the United States and Canada. Influence of age and income. AB - OBJECTIVE: To compare overall rates of coronary artery bypass surgery (CABS) in several Canadian and US jurisdictions and to compare use by age and income groups in the two countries. DESIGN: Survey, using computerized hospital discharge abstracts. SETTING: All nonfederal hospitals in New York, California, Ontario, Manitoba, and British Columbia between 1983 and 1989. PATIENTS: All adult residents of the five jurisdictions who underwent CABS in a hospital in their jurisdiction. RESULTS: Between 1983 and 1989, the CABS rates were consistently highest in California and lowest in the Canadian jurisdictions. In 1989, the age adjusted rate of CABS in California (112.5/100,000 adults) was 27% higher than in New York (88.4/100,000) and 80% higher than in the three Canadian provinces combined (62.4/100,000). The CABS rates increased for those aged 65 years and older and decreased for those aged 20 to 54 years in all five jurisdictions. In 1989, CABS rates were three times higher in California than in Canada for those aged 75 years and older, and the higher rates for those aged 65 years and older accounted for 75% of the overall difference in rates between California and Canada. In Canada, CABS rates for the nonelderly varied little by income of area of residence, but in New York and California, rates increased steadily with the income of area of residence. CONCLUSION: Control over the supply of resources in Canada is associated with markedly lower CABS rates for the elderly than found in the United States. While overall rates are lower in Canada, the Canadian universal health insurance system reduces the influence of income on access to CABS found in the United States. However, even without universal health insurance, CABS rates for the nonelderly living in the poorest areas in California are similar to the rates for those living in the poorest parts of Canada. PMID- 8455300 TI - Using 'windows of opportunities' in brief interviews to understand patients' concerns. PMID- 8455301 TI - Clinical perspectives on seabather's eruption, also known as 'sea lice'. AB - Seabather's eruption is usually a benign clinical syndrome that resolves spontaneously, although severe symptoms and long-term sequelae have been identified. Recent research has implicated the larvae of a jellyfish, Linuche unguiculata, as the cause of this syndrome; confirmation by serological and experimental studies is pending. Clinical signs and symptoms are consistent with this etiology. Outbreaks occur when jellyfish larvae are transported to shore by ocean currents. Treatment is symptomatic and involves use of antihistamines and steroids. PMID- 8455302 TI - Dear President Clinton. PMID- 8455303 TI - Childhood lead poisoning. The impact of prevention. PMID- 8455304 TI - Defining the good doctor. PMID- 8455305 TI - International editions of JAMA and the AMA specialty journals. 'Perpetuum motum in circula'. PMID- 8455306 TI - Costs, benefits, and the changing ethos of medicine. PMID- 8455307 TI - Regulated fees or regulated competition? Implications for young physicians. PMID- 8455308 TI - The cost of prevention: don't expect a free lunch. PMID- 8455309 TI - Are generalists the answer for primary care? PMID- 8455310 TI - Effects of intravenously infused egg phospholipids on lipid and lipoprotein metabolism in postoperative trauma. AB - Lipid emulsions contain not only triglyceride (TG)-rich particles but also phospholipid (PL)-rich particles that are believed to trap free cholesterol and apoprotein E, when they are infused in excess. The present study was designed to evaluate the effects of such abnormal PL-rich particles on lipid metabolism during a 5-day infusion in man. Eighteen patients undergoing esophagectomy were evenly randomized to receive intravenously during 5 days 1.75 g.kg-1.d-1 long chain TG from either a 10% lipid emulsion with a PL/TG weight ratio of 0.12 (group A), a 10% emulsion with a PL/TG weight ratio of 0.06 (group B), or a 20% emulsion with a PL/TG weight ratio of 0.06 (group C). Plasma PL, free cholesterol, and apoprotein E increased progressively in group A (4.1 +/- 0.3 mmol/L, 2.4 +/- 0.3 mmol/L, and 0.089 +/- 0.012 g/L on day 5, respectively) but not in groups B (2.7 +/- 0.3 mmol/L, 1.3 +/- 0.2 mmol/L, and 0.048 +/- 0.007 g/L) and C (2.4 +/- 0.2 mmol/L, 1.2 +/- 0.1 mmol/L, and 0.050 +/- 0.006 g/L). Free fatty acids and TGs remained constant and similar in each group postoperatively. After fat infusion had been stopped at the end of the fifth day, the elimination of plasma TGs over the next 4 hours was comparable in the three groups. We conclude that excess egg PLs induce alterations of plasma lipids even within a few days. PMID- 8455311 TI - Response of muscle protein synthesis to parenteral administration of amino acid mixtures in growing rats. AB - Previous studies have shown that 1-hour infusions of neither glucose nor an amino acid mixture alone stimulates muscle protein synthesis in postabsorptive rats (Biosci Rep 1986;6:177-183). We have therefore investigated whether longer periods of infusion are required to initiate responses. The effects of intravenous infusions of various substrates for 6 hours on rates of skeletal muscle protein synthesis in fasted rats were studied. Fractional rates of protein synthesis (ks, the percent of muscle protein renewed each day) and the ribonucleic acid activity (kRNA, the amount of protein synthesis per unit of ribonucleic acid [milligrams of protein per day per milligram of ribonucleic acid]) were measured with a flooding dose of L-[4-3H]phenylalanine. Infusion of mixed amino acids (15 mg of nitrogen per hour per rat) increased ks and kRNA by approximately 50% in comparison with saline-infused rats, but rates of muscle protein synthesis remained below those observed in fed animals. Doubling the infusion rate of amino acids to 30 mg of nitrogen per hour per rat had no additional effect on ks and kRNA, and addition of glucose (0.3 g/h per rat) or glucose plus lipid also had no significant additive effect. However, infusion of glucose alone (0.3 g/h per rat) increased ks and kRNA by 25% when compared with saline-infused controls. Infusion of the branched-chain amino acids in the same amounts as present in the amino acid mixture increased ks and kRNA by 20% compared with saline-infused controls, but the rate remained significantly lower than that obtained by infusion of mixed amino acids. PMID- 8455312 TI - Controlled trial on nutrition supplementation in outpatients with symptomatic alcoholic cirrhosis. AB - A controlled trial on nutrition supplementation in ambulatory patients with decompensated alcoholic liver disease was carried out during 1 year. Fifty-one patients were studied; 26 were assigned to an experimental group receiving a daily supplement of 1000 kcal and 34 g of proteins given as a casein-based enteral nutrition product and 25 to a control group receiving one placebo capsule. Patients were examined in a special clinic once a month or more if required. Sixty-eight percent of patients admitted to alcohol ingestion or had alcohol in urine samples on at least one occasion. Dietary recalls showed a significantly higher protein and caloric intake in case patients subjects (p < .0001). Nine patients died during the study, three case patients and six control patients (p = NS). The frequency of hospitalizations was significantly less in the experimental group. This difference was attributed to a reduction in severe infections. Mid-arm circumference, serum albumin concentration, and hand grip strength improved earlier in case patients, although both groups had a significant improvement in these parameters. Bilirubin and aspartate aminotransferase decreased and prothrombin time increased significantly in both groups during the study period, without differences between groups. It is concluded that nutrition support decreases nutrition-associated complications in patients with alcoholic liver disease. PMID- 8455313 TI - The effects of total parenteral nutrition on the hepatic handling of bilirubin in the rat. AB - Disturbances of bilirubin metabolism such as jaundice or pigment gallstone formation occur during total parenteral nutrition (TPN). We have studied the effects of TPN on bile flow and bile acid secretion and on the hepatobiliary transport of bilirubin in rats. Animals on parenteral nutrition for 5 days received 4.8 g of amino acids and 6.9 g of glucose daily. Controls were orally fed animals. Bile flow and bile acid secretion were not significantly modified by TPN. Serum bile acid and alkaline phosphatase levels were significantly increased in TPN animals when compared with the controls (+98% and +38%, respectively), which points to a relative cholestasis in the TPN rats. The biliary excretion of bilirubin monoconjugates and bilirubin diconjugates was significantly increased (+72% and +78%, respectively). This provides evidence for enhanced production of the pigment. Serum concentration of total bilirubin was enhanced in the TPN rats (+240%). The esterified/total bilirubin ratio in serum increased, whereas the bilirubin diconjugates/bilirubin monoconjugates ratio decreased. These facts, together with the minor reduction of hepatic bilirubin UDP glucuronosyltransferase activity (-12%), suggest that hyperbilirubinemia would be a consequence of both cholestasis and increased bilirubin production. The alterations reported here could contribute to the explanation of hyperbilirubinemia and pigment gallstone formation in patients maintained on parenteral nutrition. PMID- 8455314 TI - Gastrin, motilin, insulin, and insulin-like growth factor-I concentrations in very-low-birth-weight infants receiving enteral or parenteral nutrition. AB - Blood concentrations of gastrin, motilin, insulin, and insulin-like growth factor I were measured sequentially during the first 3 weeks of life in 22 very-low birth-weight infants (birth weight 1.03 +/- 0.24 g; gestational age 28.3 +/- 1.9 weeks; mean +/- SD) who were in respiratory distress requiring mechanical ventilation and were receiving either total parenteral or enteral feedings. An increase in the blood concentration of motilin beyond the basal measurement was observed in enterally fed infants but not in infants receiving total parenteral nutrition. Motilin and gastrin concentrations were significantly increased in the enterally fed group compared with infants receiving total parenteral nutrition at 2 and 3 weeks and 1 and 3 weeks, respectively. There were no differences in serum insulin or plasma insulin-like growth factor-I concentrations between groups after the start of the study. The present data suggest that enteral nutrition in very-low-birth-weight infants is associated with a relative increase in peripheral motilin and gastrin concentrations compared with parenterally fed infants. PMID- 8455315 TI - Comparison of parenteral nutrition supplemented with L-glutamine or glutamine dipeptides. AB - Although glutamine is an important fuel used by the intestinal mucosa and other visceral organs, it is not present in any commercially available parenteral amino acid solution. To compare the effects of L-glutamine with glutamine dipeptides, we studied the effects of each in 8 dogs and 60 Wistar rats. In the dog study, three amino acid solutions were compared: standard commercial amino acid solution (control), alanine-glutamine dipeptide-enriched solution (glutamine 3.4%), and glycine-glutamine dipeptide-enriched solution (glutamine 3.6%). Arterial and venous samples were collected to compare the effects of the three solutions on skeletal muscle amino acid exchange. In the rat study, two studies were undertaken: group 1 rats underwent only central venous catheterization; group 2 rats underwent central venous catheterization and a 50% intestinal resection. Within each group, three different solutions were infused: standard amino acid solution (control), glutamine-enriched (1.5% glutamine) solution, or glutamine dipeptide-enriched (1% glutamine) solution. After 7 days of parenteral nutrition, samples of gut, blood, and muscle were collected for determination of mucosal thickness, villus area, serum amino acid profile, liver and renal function tests, and muscle composition. When glutamine or glutamine-dipeptide solutions were administered, the dogs showed increasing serum glutamine concentrations and enhanced glutamine uptake across the hind leg muscle. Similarly, both groups of rats demonstrated significant differences in serum glutamine levels, nitrogen balance, intestinal mucosa thickness, and villus area. We conclude that both glutamine and glutamine-dipeptide infusions increase serum glutamine concentrations and result in regional tissue effects. Both exerted similar metabolic effects with no apparent complications. PMID- 8455316 TI - The vitamin K content of intravenous lipid emulsions. AB - Commercially available intravenous lipid emulsions are largely derived from vegetable oils, a natural source of phylloquinone (vitamin K1). We therefore examined the concentration of vitamin K1 in two widely used intravenous lipid emulsions by using a previously validated high performance liquid chromatography technique. The vitamin K1 concentrations of 10% emulsions of Intralipid and Liposyn II were 30.8 and 13.2 micrograms/dL, respectively. The concentration of vitamin K1 in the 20% emulsions of these products was essentially double that in the 10% emulsions. The coefficients of variation between the vitamin K1 content in three different lots of each product were consistently less than 7.0%. The observed concentrations of the vitamin in these lipid emulsions paralleled the predicted content on the basis of the type of vegetable oil(s) used to make the product. The type of vegetable oil used for production therefore seems to be a major determinant of the final vitamin K1 content. The vitamin K1 contained in these intravenous lipid emulsions is substantial and may have great impact on the vitamin K status of the recipient. PMID- 8455317 TI - Peripheral parenteral nutrition: a preliminary report on its efficacy and safety. AB - In this preliminary study of peripheral parenteral nutrition, we compared our first nine patients fed by this method with 21 patients fed by total parenteral nutrition during the same period. We found that peripheral parenteral nutrition was as effective as total parenteral nutrition in improving physiologic function (both skeletal and respiratory muscle function). We also found that by using the protocol described here thrombophlebitis was not a significant problem. Additional study is required to ascertain the exact incidence of this and other complications. We would advocate the greater use of peripheral parenteral nutrition in suitable patients and the use of this protocol for its administration. PMID- 8455318 TI - Structured triglycerides to postoperative patients: a safety and tolerance study. AB - Long-chain triglycerides are still the standard in fat emulsions, although medium chain triglycerides have been suggested to have metabolic advantages even though pure medium-chain triglycerides are toxic in large doses. The next generation of fat emulsions may be structured triglycerides, which are assumed to provide a higher oxidation rate, faster clearance from blood, improved nitrogen sparing, and less of a tendency to accumulate in the reticuloendothelial system compared with long-chain triglyceride emulsions. This study was designed to evaluate the safety and tolerance of structured triglyceride fat emulsion 73403 (Kabi Pharmacia Parenterals, Stockholm, Sweden) compared with that of a standard long chain triglyceride emulsion (Intralipid 20%) in postoperative patients requiring total parenteral nutrition after major surgery. The study was randomized and of the double-blind, parallel group type. Twenty patients were included and treated for 5 to 7 days. Safety and tolerance variables demonstrated no major differences between the study and control groups. Physiologic and biochemical variables suggested that structured lipids were rapidly cleared and metabolized. This study represents the first report of administration of structured triglycerides to postoperative patients. The structured triglyceride emulsion (73403) demonstrated no difference in safety and tolerance compared with Intralipid 20%. Therefore, it will now be possible to follow up with studies on metabolic efficiencies of structured triglycerides in postoperative patients. PMID- 8455319 TI - Metabolic rate and nitrogen balance in patients receiving bolus intermittent total parenteral nutrition infusion. AB - The present study investigated whether infusion principles are significant factors that influence the nutritional efficiency of complete intravenous nutrition. For this purpose, three infusion modalities were evaluated in patients who underwent elective and uncomplicated cholecystectomy. The nutrition regimens were as follow: group 1, sequential infusion of fat plus amino acids at a constant rate over 12 hours during daytime followed by glucose infusion at a constant rate for 12 hours during nighttime; group 2, simultaneous infusion of all substrates at a constant rate over 24 hours; and group 3, simultaneous infusion of all substrates with bolus-based intermittent infusions during 60 minutes six times per day (24 hours). Nonprotein calories corresponded to 160% of the individually measured resting need and were provided as 60% carbohydrate and 40% fat. Nitrogen was provided as crystalline amino acids in solution at 0.2 g of nitrogen per kilogram per day. All patients were randomized into three comparable groups. Intermittent nutrition (group 3) was associated with a significantly higher thermic effect, which led to a significantly lower although still positive energy balance than either sequential nutrition (group 1) or constant nutrition (group 2). The mean daily nitrogen balance was, however, significantly improved in patients receiving intermittent nutrition, and this was accompanied by much higher plasma insulin levels as well as higher plasma amino acid concentrations. This study demonstrates that all substrates should be given simultaneously and that supplementation of intravenous nutrition in boluses, similar to meal feeding, gave the most pronounced protein accretion when compared with either sequential administration of total parenteral nutrition or administration of all admixtures with constant infusion over 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455320 TI - Effect of glutamine-supplemented total parenteral nutrition on recovery of the small intestine after starvation atrophy. AB - Intestinal atrophy was induced in rats by infusion of 5% dextrose for 7 days with only oral water allowed. Compared with control animals fed standard rat chow (Purina Mills, St. Louis), the starved animals lost 30.5% of their initial body weight, 34.7% mucosal wet weight, 68.3% mucosal nitrogen content, 36.7% mucosal thickness, and 38.6% villous height and had variable losses of mucosal disaccharidase activities. Three groups of depleted rats were then refed with different regimens. One group was refed with standard Purina rodent chow (n = 15); a second group with a standard total parenteral nutrition (TPN) solution containing 16% glucose, 2.8% fat, and 4.25% standard amino acids (Travasol 8.5%, Baxter Healthcare Corporation, Deerfield, IL) (n = 15); and the third group with a TPN solution of 16% glucose, 2.8% fat, 2.75% standard amino acids, and 1.5% glutamine (n = 15). After 7 days of refeeding, rats were killed to determine the degree of intestinal recovery. Animals refed with standard TPN solution showed no significant recovery of intestinal mucosal weight, mucosal nitrogen content, villous height, mucosal thickness, or mucosal disaccharidase activities. Animals refed with glutamine-supplemented TPN solution demonstrated significant recovery of all parameters but not back to normal. Oral rodent chow completely restored intestinal anatomy and function. The addition of glutamine to TPN solutions significantly improved recovery of the intestine from starvation atrophy, and additional efforts to make it commercially available are indicated. This study again confirms the preferable use of a regular oral diet when clinically feasible and safe. PMID- 8455321 TI - Amino acid infusions induce reversible, dose-related decreases in bile flow in the isolated rat liver. AB - Parenteral infusion of amino acid solutions is known to produce cholestasis in experimental animal models and in the isolated perfused rat liver. To characterize the dose responsiveness and reversibility of amino acid-induced cholestasis, isolated rat livers were perfused with solutions containing 1.5, 3.0, or 6.0 g of amino acids for 1 hour and allowed to recover for 30 minutes. Perfusion of livers resulted in a rapid, dose-related decrease in bile flow (p < .0001 at doses of 3.0 and 6.0 g). When the amino acid solution was discontinued, bile flow recovered to near control rates. Infusion of taurocholate reduced the magnitude of the decrease in bile flow associated with amino acid infusion but did not prevent it. Infusion of amino acid solutions was associated with the following changes in bile: (1) dose-related increases in total free amino acid concentrations; (2) increased osmolarity; (3) increased glucose concentrations; (4) increased potassium concentrations; (5) decreased chloride concentrations; (6) increased oxygen uptake in livers not perfused with added taurocholate; and (7) increased total bile acid concentrations in livers perfused with added taurocholate. Additional investigations are needed to determine whether these associations are attributable to individual amino acids or the total metabolic load of the amino acids. PMID- 8455322 TI - Volume of blood required to obtain central venous catheter blood cultures in infants and children. AB - To determine how much blood must be discarded before one can obtain a reliable central venous catheter blood culture, we prospectively cultured the blood (from 96 patients) that is ordinarily discarded before obtaining blood for such a culture. We then compared the prospective culture results with those of the actual blood culture. Three sequentially drawn aliquots of blood were aspirated from the central venous catheter and cultured. The culture results of the second aliquot were comparable to those of the third (the portion usually cultured) in overall sensitivity (94.4%), specificity (94.9%), and positive predictive value (80.9%). Thus, the amount of blood that must be discarded (infants: 0.3 mL; children: 1.0 mL) before one can obtain an accurate central venous catheter culture is less than was previously thought. PMID- 8455323 TI - Medication delivery in the short-bowel syndrome. AB - Technologic advances such as total parenteral nutrition have prolonged the lives of individuals with short-bowel syndrome who previously would not have survived. However, the day-to-day management of these patients presents a significant challenge to those who take care of them. Providing medications on either an acute or chronic basis without the use of their central catheters is a difficult clinical problem. This article reviews the approach and methods of treating short bowel patients on the basis of their individual circumstances and physiology. PMID- 8455324 TI - Large-bore feeding tube occlusion by yeast colonies. AB - This is a first report of three patients with silicone feeding tubes (two with percutaneous endoscopic gastrostomies and one with a jejunostomy, all 20 French catheters) that have formed a thick yeast crust on the inner luminal surface causing tube occlusion in two cases. Candida species were isolated in all three tubes. The yeast crust could not be removed with a brush or with fungicidal drugs such as nystatin and amphotericin B. Histologic sections through these feeding tubes revealed yeast penetration through the silicone material, explaining the adherent nature of the crust. This complication may also explain the observed material deterioration with subsequent breakage. PMID- 8455325 TI - Nutritional outcome and pneumonia in critical care patients randomized to gastric versus jejunal tube feedings. PMID- 8455326 TI - Effect of intraportal glucose infusion on hepatic glycogen content and degradation, and outcome of liver transplantation. PMID- 8455327 TI - Outcome of home parenteral nutrition. PMID- 8455328 TI - [Microbiological determination of netilmicin using a thin-layer chromatography scanner]. AB - We presented a new colorimetric bioassay of aminoglycoside antibiotics, which were represented by netilmicin (NTL) in this study, based on the discoloration of thymolphthalein (TP) in paper (indicator-disc) by carbon dioxide produced by Bacillus subtilis. To evaluate the amount of the carbon dioxide, the following experiment was carried out. One milliliter of B. subtilis suspension containing 4.5 x 10(7) colony forming units/ml, 1 ml of nutrient broth, 0.9 ml of 0.1 M phosphate buffer (pH 8.0) and 0.1 ml NTL sample solution were added to an incubation container, which was then placed in a water-bath (37 degrees C) for 3 hours. The oxygen concentration in the head space of flask was determined using gas-chromatograph. The dose-response curves showed good correlation between amounts of NTL and carbon dioxide produced by B. subtilis. The indicator-disc containing TP and sodium hydroxide was placed into the Reacti-flask and then incubated in the same manner as described above. After incubation, concentration of blue colored TP was determined using a TLC scanner. The discoloration of blue color to white showed the proportionality between NTL concentrations and the degrees of discoloration of TP. The method can accurately measure NTL levels down to 2.5 micrograms/ml in water using 0.1 ml samples, and should be adequate for rapid bioassay. PMID- 8455329 TI - Pharmacological effects of cefclidin on the central nervous system. AB - The effects of cefclidin (CFCL), a novel antibacterial agent, on the central nervous system (CNS) were examined in a variety of animal models. The effects of cefazolin (CEZ) were also examined for comparative purposes. In the animal models used CFCL whilst having some effects at the doses examined, failed to show an overall consistent effect on the CNS. In contrast CEZ produced changes in the parameters measured which were generally consistent with a proconvulsant action. PMID- 8455330 TI - [Cefuzonam penetration into cerebrospinal fluid]. AB - We studied the penetration of cefuzonam (CZON) into the cerebrospinal fluid (CSF) in 20 patients with neurosurgical diseases. Influences of the presence of meningeal reaction and the intensity of brain damage on CSF penetration of CZON were also examined. Concentrations of CZON in serum and CSF were determined using the thin-layer cup method before and 1, 2, 4, and 6 hours after 2 g of CZON was administered intravenously. The serum concentration at 1 hour was 60.4 +/- 31.3 (mean +/- S.D.) microgram/ml, then rapidly decreased to 2.1 +/- 2.3 micrograms/ml at 6 hours. In contrast, the CSF concentration gradually increased, reached a peak level of 0.319 +/- 0.313 micrograms/ml at 4 hours and then slowly decreased to 0.273 +/- 0.249 micrograms/ml at 6 hours. The CSF penetration ration: CZON ([CSF]/[serum]) was 5.6% at 4 hours. The peak CSF concentration in patients with meningeal reaction (0.465 +/- 0.364 micrograms/ml at 2 hours) was about 2-fold higher than that in those without the reaction (0.249 +/- 0.223 micrograms/ml at 4 hours). The peak CSF concentrations in patients with slight, moderate, and severe brain damage were 0.231 +/- 0.133 micrograms/ml at 4 hours, 0.270 +/- 0.232 micrograms/ml at 4 hours, and 0.680 +/- 0.467 micrograms/ml at 2 hours, respectively. CSF penetration of CZON was augmented in patients with meningeal reaction or severe brain damage. These findings indicate that the concentration of CZON in CSF after intravenous administration is sufficient for treatment of meningitis or infections after neurosurgical operations caused by such bacteria as Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, and Streptococcus pneumoniae. PMID- 8455331 TI - [Clinical evaluation of cefpodoxime in respiratory tract infections]. AB - Cefpodoxime (CPDX-PR) was evaluated clinically in respiratory tract infections. The results obtained are summarized as follows; 1. The total number of the patients who were treated with CPDX-PR was 61, out of whom 53 cases were evaluated for clinical efficacy and 55 cases were investigated for the safety of the drug. CPDX-PR was given orally twice a day at 100-200 mg for 5-21 days. 2. Clinical efficacies were excellent in 9 patients, good in 36, fair in 4 and poor in 4. The overall clinical efficacy was 84.9%. In particular, CPDX-PR showed satisfactory efficacy for acute respiratory infections and mild chronic respiratory infections, with efficacy rates of 88.6% (31/35) and 100% (8/8), respectively. 3. No adverse reactions was observed, but slight and transient elevation of BUN was noted. In conclusion, it has been confirmed that CPDX-PR is an excellent and safe drug for the treatment of the respiratory tract infections. PMID- 8455332 TI - [Clinical studies of ofloxacin 300 mg once a day administration in chronic respiratory tract infections]. AB - Forty patients with chronic respiratory infections were randomly assigned to 2 groups to compare the effect of once daily administration of 300 mg each and 3 times daily administration of 600 mg each of ofloxacin (OFLX). Twenty patients were administered with 300 mg OFLX a day and 18 cases received 600 mg. The number of underlying diseases in the 300 mg group was greater than that in the 600 mg group. The ratios of general amelioration of clinical symptoms were 80.0% in the 300 mg group and 88.9% in the 600 mg group. For bacteriological effects, the eradication rate was 80.0% in the 300 mg group and it was 84.6% in the 600 mg. The incidence of side effects in the 300 mg group was 0% and that of the 600 mg group was 5.6% (1 patient) but the symptom was mild. The incidence of abnormal laboratory test results was 15.0% in the 300 mg group and it was 11.2% in the 600 mg group, but all of these abnormalities were slight and transient. The safety rates in the 300 mg and the 600 mg groups were 95.0% and 94.4%, respectively. Efficacy rates in the 300 mg and the 600 mg groups were 80.0% and 88.9%, respectively. There was no statistically significant difference in all the results between the 2 treatment groups, and the both treatments were highly effective. From the above results, we consider that once daily administration of 300 mg is a useful therapy in respiratory tract infections. PMID- 8455333 TI - [Pharmacokinetic and clinical studies on DQ-2556 in the gynecological field]. AB - Pharmacokinetic and clinical studies on DQ-2556, a new cephem antibiotic, in obstetrics and gynecology were performed and following results were obtained. Concentrations of DQ-2556 were determined in serum, internal genital organs and retroperitoneal exudate after single intravenous administration (i.v.) or drip infusion (d.i.v.) of 1.0 g. Serum levels following i.v. were approximately 30 micrograms/ml at 1 hour, 14 micrograms/ml at 3 hours 30 minutes, and concentrations in internal genital organs including oviduct, ovary, endometrium, myometrium, cervix uteri and portio vaginalis reached approximately 50% to 70% levels of serum concentration. The mean concentration (n = 6) in the retroperitoneal exudate after d.i.v. of 1.0 g following radical hysterectomy were about 20 micrograms/ml, 23 micrograms/ml, 14 micrograms/ml and 8 micrograms/ml at 1 hour, 2 hours 30 minutes, 4 hours 30 minutes and 6 hours 30 minutes, respectively. In clinical trials, DQ-2556 (2.0 g b.i.d. for daily dose) was given in 5 patients with gynecological infections such as pyometra (1 case), salpingitis (1), retroperitoneal space infection (2), pelvic peritonitis (1). The clinical results were evaluated as good in 3 cases and poor in 2 cases including a case with salpingitis infected by Pseudomonas aeruginosa and the other with pelvic peritonitis caused by Methicillin-resistant Staphylococcus aureus. Bacteriologically, 11 organisms were isolated from patients, and eradication rate was 54.5%. Neither side effect nor abnormal laboratory test result was observed. Thus, DQ-2556 appears to be effective for gynecological infections, and the good results were supported by good penetration of the compound into tissues of internal genital organs and retroperitoneal exudate after i.v. or d.i.v. PMID- 8455334 TI - [Clinical long-term studies of the treatment of chronic complicated urinary tract infections. Utility and recurrence after 14-day treatment by cefditoren pivoxil]. AB - In this study, cefditoren pivoxil (ME 1207, CDTR-PI), a new oral cephem antibiotic, was given to 72 patients with non-catheterized complicated urinary tract infections (UTI) to evaluate clinical efficacy and safety, and also to investigate the rate of recurrence after completion of treatment. Daily dose of CDTR-PI was 100 mg t.i.d., and CDTR-PI was administered for 14 days. According to the criteria proposed by the Japanese UTI Committee, clinical efficacy of CDTR-PI was evaluated at day 7 and day 14. The rate of recurrence was assessed by bacterial count in urine as the marker. The following results were obtained. 1. Overall clinical efficacy rates were 68.4% on day 7 and 81.6% on day 14. The efficacy rate at day 14 was higher than the rate at day 7. 2. Bacteriologically, eradication rates were 75.5% at day 7 and 79.6% at day 14. 3. As to side effects, abdominal discomfort was observed in 1 case and its incidence was 1.6%. Incidence of abnormalities of laboratory findings was 10.4%, and these abnormalities were slight and transient. 4. Thirty-one patients were assessable to the recurrence of infections, 60% of them were judged as "cured" at 1-2 weeks and 3-7 weeks after completion of treatment. In this study, "relapsed", reappearance of causative organisms, was observed much more frequently than "reinfection". These results suggest that sufficient clinical efficacy and safety of CDTR-PI in non catheterized complicated UTI were effected by 14 days treatment. PMID- 8455335 TI - [Effects of a combination therapy consisting of arbekacin and ampicillin of methicillin-resistant Staphylococcus aureus]. AB - Investigations were made on effects of a combination therapy consisting of arbekacin (ABK) and ampicillin (ABPC) against methicillin-resistant Staphylococcus aureus (MRSA). The following conclusions were drawn. 1. A frequency of FIC index to be < or = 0.5 upon a combination therapy consisting of ABK and ABPC against MRSA was 48.7%, hence this therapy showed better antibacterial effects than the other 8 combination therapies consisting of ABK and other antibiotics previously studied. 2. A combination therapy consisting of ABK and ABPC against MRSA was better than any other combination therapy because ABPC had a higher binding affinity with penicillin-binding protein 3 of MRSA, and because a high antibacterial activity of ABPC was maintained during the combination therapy. ABPC did not lose antibacterial activity largely because MRSA dose not produce beta-lactamase, or most of MRSA produces little beta lactamase activity. 3. Our data indicate that the success of a combination therapy against MRSA depends upon the effects of the drug under sub MIC concentrations. PMID- 8455336 TI - [Pharmacokinetic and clinical studies of cefditoren pivoxil in the pediatric field. Pediatric Study Group of ME1207]. AB - Cefditoren pivoxil (ME1207) in granules, a new oral cephalosporin, was pharmacokinetically and clinically evaluated in the pediatric field and the following results were obtained: 1. Pharmacokinetics In infants administered single oral doses of 3 mg (potency)/kg and 6 mg/kg, the Cmax was 1.54 +/- 0.68 and 2.85 +/- 1.03 micrograms/ml; Tmax, 2.27 +/- 1.08 and 2.06 +/- 1.16 hours; T 1/2, 2.22 +/- 1.95 and 1.68 +/- 0.66 hours; and AUC (0-infinity), 7.43 +/- 3.68 and 11.90 +/- 4.51 micrograms.hr/ml, respectively. These values have indicated that the drug has a dose-dependent pharmacokinetic behavior. Urinary concentrations peaked in 2-4 hours after administration. Urinary recovery rates in the first 8 hours were 19.4 +/- 6.6% at 3 mg/kg and 17.1 +/- 5.2% at 6 mg/kg. 2. Clinical results The clinical efficacy of the drug was evaluated in 445 patients with various infections. Cefditoren pivoxil was administered at daily doses of 9-18 mg/kg divided into 3 equal doses to most patients. Daily doses of > 7.5-10.5 mg/kg were given to 48.8% of the patients. The overall clinical efficacy rate was 97.3%, and this drug was effective in 97.5% of the 319 patients for whom the causative pathogens were identified and in 96.8% of the 126 patients with infections for whom the causative pathogens were unknown. The efficacy rate at daily doses of > 7.5-10.5 mg/kg was 97.2%, similar to that obtained at daily doses of > 10.5-19.5 mg/kg (97.0%). The bacteriological eradication rate was 90.4%. The efficacy and eradication rates for 66 patients who had not responded to previous chemotherapy were 95.5% (63/66) and 89.4%, respectively. Side effects occurred in 19 (4.2%) of 456 patients subjected to safety analyses. The primary side effect was diarrhea but no serious side effects were noted. As abnormal laboratory test results, moderate increases of the eosinophils and platelets counts as well as moderate elevations of the transaminases were observed. These abnormalities are also seen with other cephems and to a similar extent. No particular and serious problems were associated with administration of this drug. Based on the above results, cefditoren pivoxil is considered to be very useful at a dose level of 3 mg/kg t.i.d. against most infections encountered in the pediatric field. PMID- 8455337 TI - [Quantitation of regional myocardial blood flow using continuous inhalation of C15O2 and positron emission tomography]. AB - A C15O2 continuous inhalation and a steady-state theory using positron emission tomography (PET) have been used to quantitate regional cerebral blood flow. We extended this method for quantitative regional myocardial blood flow (RMBF) measurement. Forty-three patients, involving 4 normal volunteers, 16 patients with coronary heart disease (CHD), 20 patients with hypertrophic cardiomyopathy (HCM), and 3 patients with dilated cardiomyopathy (DCM), were studied. 6 min-scan was recorded in the steady-state condition during C15O2 continuous inhalation. A C15O inhalation scan was required to obtain the blood pool image. The subtracted image showed myocardial perfusion image. These images demonstrated homogeneous accumulation in normal volunteers. Reduced accumulation were detected in patients with myocardial infarction. Hypertrophied myocardium was demonstrated in patients with HCM. Diffuse heterogeneous accumulation was demonstrated in patients with DCM. Fourteen patients with HCM, whose left ventricular myocardial thicknesses were more than 20 mm, were selected for the RMBF measurement to minimize errors due to the partial volume effect. The arterial blood activity was measured by assigning a region of interest to the left atrial cavity on PET images. RMBF was calculated using the steady-state theory. Calculated flow values ranged from 21.2 to 152.6 ml/min/100 g. The good correlation was obtained between RMBF using 13NH3 first pass method and RMBF using gas inhalation method in six patients. These results indicate that C15O2 PET has the potential capability for the noninvasive quantitation of RMBF. PMID- 8455338 TI - [A technique for a rapid imaging of regional CBF and partition coefficient using dynamic SPECT and N-isopropyl-p-[123I]iodoamphetamine (123I-IMP)]. AB - IMP is a flow tracer due to a large first pass extraction fraction and high affinity in the brain, but significant clearance from the brain causes change of distribution when the scan start time is delayed. The purpose of the present study is to develop a new method to rapidly calculate a quantitative CBF image by taking into account for the clearance effects. A dynamic SPECT scan was performed on 5 subjects (4 patients with cerebral infarction and 1 normal volunteer) following slow intravenous infusion of 123I-IMP. The arterial input function was obtained by frequent blood sampling and by measuring an octanol extraction ratio for each sample. Firstly, non-linear least square fitting (NLS) was performed to investigate the tracer kinetics of 123I-IMP. The 3 compartment model analysis yielded negligibly small k3 (retaining rate constant) (0.0056 +/- 0.0128 (ml/ml/min)), and consistent k1 (transport rate constant) with those determined by 2 compartment model (2CM) analysis (r = 0.96, p < 0.001). In addition, k1 was consistent with CBF measured by 15O water PET technique. These observations suggested validity of using 2CM for describing the IMP tracer kinetics. Secondly, a weighted integration (WI) technique has been implemented to calculate rapidly images of CBF and partition coefficient (Vd). The WI technique yielded values of CBF (k1) and Vd (k1/k2). They were confirmed to be consistent with those determined by NLS technique (CBF; r = 0.99, p < 0.001, Vd; r = 0.99, p < 0.001), and calculated k1 agreed well with PET CBF (r = 0.91, p < 0.001). We observed changed Vd in infarcted patients. This supports an importance for calculating of Vd image. Vd image will provide additional clinical information because 123I-IMP binding mechanism may be related to cell viability. PMID- 8455339 TI - [Evaluation of the safety and clinical usefulness of a new myocardial imaging agent, 99mTc-PPN1011--multicenter phase II clinical trial report]. AB - A new myocardial perfusion imaging agent, 99mTc-1,2-bis[bis(2-ethoxyethyl phosphino]ethane (99mTc-PPN1011) was administered to 52 patients with various heart diseases each at rest and peak exercise on different days (Method A) and on the same day (Method B). The safety, optimal dosage, imaging procedures and the clinical usefulness were evaluated. No drug related adverse reactions were found. Image quality was considered adequate for diagnosis with as little as 185 MBq per injection, though the optimal dose range was 370-740 MBq. SPECT images were obtainable as early as 10 min, also until 3 hours after injection. There were no significant differences in clinical efficacy between method A and B, as well as sequential tests at rest and exercise. 99mTc-PPN1011 and 201T1 images in the same patient were compared segment by segment. Image quality of 99mTc-PPN1011 was significantly superior to that of 201T1. Analysis of images indicated that both agent were similar in diagnostic efficacy. It was concluded that 99mTc-PPN1011 is useful for myocardial perfusion imaging. PMID- 8455340 TI - [Assessment of congenital heart disease by a thallium-201 SPECT study in children: accuracy of estimated right to left ventricular pressure ratio]. AB - The characteristics of correlation between the right-to-left ventricular systolic pressure ratios (RVp/LVp) and the thallium-201 right-to-left ventricular (201Tl R/L) count ratios was investigated in children with various congenital heart diseases. High-resolution three-headed SPECT system equipped with either parallel hole or fan-beam collimators was used. In a total of 102 patients, the correlation between RVp/LVp and 201Tl R/L average count ratios was good in both planar (r = 0.89, p = 0.0001) and SPECT studies (r = 0.80, p = 0.0001). Quantitative analysis of myocardial uptake by SPECT demonstrated the characteristic pattern of each disease as well as the differences in the right ventricular overload types. When the linear regression analysis was performed in each heart disease, ventricular septal defect showed most excellent correlation. Complex heart anomalies also showed positive correlation (r = 0.51, p = 0.05) with RVp/LVp, and it can be used to estimate right ventricular pressure. After surgical treatment of tetralogy of Fallot and pulmonary stenosis, the decrease of 201Tl R/L count ratio was in accordance with improvement of right ventricular overload. We conclude that 201Tl SPECT study can be a good indicator for estimation of right ventricular pressure. PMID- 8455341 TI - [131I-therapy of differentiated thyroid carcinoma with distant metastases- relation between absorbed dose by quantitative SPECT and outcome of the patients in thyroid carcinoma]. AB - The correlation of absorbed doses of tumors in 18 patients of differentiated thyroid carcinoma with distant metastases, who were treated by 131I and followed over 5 years, with their outcome were analyzed and the clinical significance of determination of absorbed dose was discussed. Radioactivities of 131I in the tumors were measured by using SPECT at the time of therapy. Absorbed dose was calculated based on the MIRD equation. Outcome of 8 patients were evaluated as good and their absorbed dose was 10-630 Gy with 2-22 g of tumor volume, 1.2-3.5 days of effective half life (EHL) and follow-up term was 8.6 +/- 0.9 years. The absorbed dose of 10 patients whose outcome were evaluated as poor, was 5-81 Gy with 7-215 g of tumor volume, 1.3-5.3 days of EHL and follow-up term was 5.6 +/- 2.5 years. The initial treatment seemed to be important for 131I therapy, since the absorbed doses in the following therapy became reduced. When the absorbed dose of the tumor exceeded over 94 Gy at initial treatment, good clinical courses were obtained. These results indicate that the quantitative SPECT for 131I therapy is clinically valid and that the calculated absorbed doses correlate well with outcome of the patients. PMID- 8455342 TI - [A case of stunned myocardium with marked 99mTc-PYP accumulation]. AB - A 71-year-old woman with unstable angina was admitted to our department. Upon admission, electrocardiography revealed a QS pattern in Leads V1-V3. Left ventriculography disclosed akinesis of the anterior wall and the septum. Myocardial scintigraphy with 99mTc-pyrophosphate (PYP) revealed marked accumulation (Parkey's grade III) in the anterior wall, septum and apical region. Coronary arteriography revealed stenosis (99% with delay) in the LAD #6. Based on these findings, we performed percutaneous transluminal coronary angioplasty (PTCA) on this patient. About 3 months later, the patient underwent PTCA again because stenosis had recurred. The resting 201Tl myocardial scintigram, taken immediately after the first PTCA, demonstrated complete defects in the anterior wall, septum and apical region. After the second PTCA, no stenosis was observed. About 1 year later, the wall motion returned to normal (except in part of the apical region), suggesting that this was a case of stunned myocardium. On the same occasion, the 201Tl uptake was normal except in the apical region. The present case was regarded as stunned myocardium which demonstrated marked radioactivity accumulation when examined by 99mTc-PYP myocardial scintigraphy. In the past, 99mTc-PYP has been thought to be incorporated into irreversibly impaired myocardium (e.g., in cases of acute myocardial infarction). The uptake of 99mTc-PYP into stunned myocardium has not been reported before. Thus, this case is rare and noteworthy. PMID- 8455343 TI - [Effect of verapamil on myocardial ischemia in patients with hypertrophic cardiomyopathy: evaluation by exercise 201Tl SPECT]. AB - Effect of verapamil on myocardial ischemia in patients with hypertrophic cardiomyopathy (HCM) was evaluated by exercise stress myocardial 201Tl SPECT (EX Tl). EX-Tl were performed before and after 8.8 weeks of oral verapamil (240 mg/day) in 12 patients with HCM who showed transient 201Tl perfusion defects under control conditions. 201Tl perfusion defect was visually scored and judged for 4 grades as normal (0), mild defect (1), moderate defect (2), and severe defect (3). Transient Dilation Index (TDI) was calculated as an index of subendocardial ischemia. Improvements of defect score were demonstrated in 10 patients after administration of verapamil. Two patients showed no change of defect score. Mean defect score decreased significantly from 5.50 to 3.03 (p < 0.001). Although 11 of 12 patients showed abnormal TDI under control conditions, 10 of them revealed improvements of TDI and 7 of those 10 patients disclosed normal TDI after verapamil. Mean TDI decreased from 1.263 to 1.090 significantly (p < 0.01). In conclusion, verapamil may improve myocardial ischemia in patients with HCM. PMID- 8455344 TI - [Usefulness of 201TlCl SPECT for evaluation of treatment effect of pancreatic cancer]. AB - To assess the treatment effect of pancreatic cancer, thallium 201 chloride (201TlCl) SPECT was performed in three patients. All of the patients before and after treatment showed the same change between the tumor/liver uptake ratio of 201TlCl and the serum level of CA 19-9. In one of the patients, tumor shrinkage was not observed on CT. However, the uptake ratio decreased, accompanying with a reduced serum level of CA 19-9. These results indicate that 201TlCl SPECT is useful to evaluate therapeutic effect of pancreatic cancer. PMID- 8455345 TI - [Perfusion imaging with 99mTc PPN-1011 for the assessment of myocardial area at risk and the efficacy of PTCA/PTCR in myocardial infarction and unstable angina]. AB - The determination of the myocardium at risk before intervention and the change in that region after intervention constitute a promising measurement tool for the assessment of acute therapy. We used 99mTc PPN-1011 in 4 patients with acute myocardial ischemia (2 patients with acute myocardial infarction, 2 unstable angina) and subsequent successful reperfusion. All 4 patients had perfusion defect on the pre-reperfusion image. Perfusion abnormality on post-reperfusion image was all improved significantly compared with pre-reperfusion image, suggesting the efficacy of acute treatment in acute myocardial ischemia. We conclude that 99mTc PPN-1011 scintigraphy is useful method for the assessment of myocardial area at risk and the efficacy of PTCA/PTCR in myocardial infarction and unstable angina. PMID- 8455346 TI - [Comparison between 180 degrees and 360 degrees data collection in 99mTc Tetrofosmin SPECT of the myocardium]. AB - We compared 360 degrees data collection technique with 180 degrees technique in SPECT using a new myocardial perfusion imaging agent, 99mTc-Tetrofosmin. Eight patients were examined at stress and at rest on separate days. Following the injection of 555 MBq 99mTc-Tetrofosmin, 64 views of 15 sec each were collected during a 360 degrees rotation, and 32 views of 30 sec each during a 180 degrees rotation. The 180 degrees data collection provided superior images in sharpness in 14 of 16 scans. The interpretation was concordant in 123 of 128 regions (96.1%), and hypoperfusion was considered to be underestimated in 5 regions using the 360 degrees technique. It was suggested that the 180 degrees data collection technique is more effective in myocardial SPECT employing 99mTc-Tetrofosmin than the 360 degrees technique. PMID- 8455347 TI - [Changes of pulmonary perfusion in the lung area unaffected by embolism]. AB - Observation of serial pulmonary scintigraphies after the treatment in the patients with pulmonary thromboembolism revealed altered perfusion in the lung area unaffected by embolism in 2 cases. Also, showed that recovered perfusion of the embolized lung area influenced the perfusion of contralateral embolic lung area in 1 patient. These findings were detected and confirmed by comparison of the serial scintigraphies mutually. These results indicate that the serial scintigraphy is useful not only for assessing perfusion recovery but also for detecting altered perfusion in the lung area unaffected by the embolism. PMID- 8455349 TI - [33rd annual meeting of the Japan Society of Chest Diseases. Yokohama, April 8 10, 1993. Abstract]. PMID- 8455348 TI - [The usefulness of three dimensional imaging of the myocardium using three heads SPECT camera (PRISM-3000)]. AB - The SPECT unit using a 3 heads camera (PRISM-3000) has an advantage over the conventional one head camera SPECT unit because it can complete full circle scans (360 degrees scans) within a short time, and because the non-circular orbit of the camera heads fitting the individual form of the body has improved the spatial resolution. In addition, the high speed data processing has reduced the time for scan, enabling the three dimensional imaging system clinically applicable. In the present study, this modern technique was used to examined the myocardium in patients with ischemic heart disease so as to evaluate it for usefulness and depict problem to be solved. In patients with myocardial infarction, images obtained with a PRISM-3000 machine could provide more objective information on infarcts than conventional images. In patients with angina pectoris, delayed images obtained 3 hours after exercise by the new method were superior to conventional ones in power of demonstrating redistribution. The setting of the threshold for ischemic lesions at 40-50% hampers the assessment of the severity of ischemia. A new program should be introduced to solve this problem. PMID- 8455350 TI - [68th annual meeting of the Japanese Society for Tuberculosis. Tokyo, April 5-6, 1993. Abstracts]. PMID- 8455351 TI - Pathophysiology of experimental nonoliguric acute renal failure. PMID- 8455352 TI - Autosomal-dominant polycystic kidney disease in the rat. AB - Kaspareit-Rittinghausen described a rodent model of inherited polycystic kidney disease (PKD), the Han:SPRD rat [1, 2], in which heterozygotes develop renal cysts and renal failure (in males) over several months, whereas homozygous animals develop rapidly progressive renal enlargement that leads to death in a few weeks. In this study, we examined selected elements of the pathogenesis of this disease in heterozygotes and homozygotes from birth to advanced disease. Heterozygous male rats developed slowly progressive renal cystic disease with interstitial fibrosis and azotemia seen by six months of age. Female heterozygotes developed slowly progressive renal cystic disease, but did not develop interstitial fibrosis or azotemia. Epithelial cells lining cyst cavities showed various degrees of morphologic immaturity. Cyst walls also developed basement membrane thickening, especially in areas of cellular immaturity, suggesting an interrelationship between this basement membrane thickening and cellular dedifferentiation. Thickened basement membranes were associated with increased immunoreactivity for type IV collagen, laminin, and fibronectin. Homozygous rats developed massive renal enlargement, marked azotemia, and died near three weeks of age. Renal c-myc proto-oncogene expression was elevated in homozygous cystic infants and in adult heterozygotes. In situ hybridization showed high levels of c-myc mRNA in cyst epithelia, suggesting abnormal regulation of cellular proliferation in the cells lining cysts, as seen in other models of PKD. The Han:SPRD rat is the only well-documented animal model of inherited PKD with an autosomal-dominant inheritance pattern and appears to have several features which resemble human ADPKD. PMID- 8455353 TI - Soluble aggregates of IgG and immune complexes enhance IL-6 production by renal mesangial cells. AB - Primary rat mesangial cells (MC) were cultured in RPMI-1640 containing 5% fetal calf serum (FCS). The cells produced interleukin-6 (IL-6) in vitro depending on the concentration of FCS in the medium. Binding of soluble aggregates of IgG (AIgG) to MC was visualized with AIgG coupled with aminomethyl coumarin acetic acid (AMCA). There was a dose-dependent binding of 125I-AIgG to MC at 4 degrees C. Scatchard analysis revealed binding of AIgG containing 20 to 24 molecules per aggregate, with an affinity of 2.2 x 10(8) M-1 and a total average number of 2.7 x 10(5) sites per cell. The binding of AIgG or immune complexes to MC resulted in enhanced production of IL-6 by MC in culture. This enhanced production of IL-6 was dependent on the concentration of AIgG. To our surprise, preparations of monomeric IgG (mIgG) also enhanced the production of IL-6 by MC, but to a lower extent when compared to levels induced by AIgG. Very little amounts of aggregated F(ab')2 fragments [AF(ab')2] bound to MC and consequently no significant enhancement of IL-6 release by AF(ab')2 was seen, suggesting that IL-6 production is an Fc receptor-mediated phenomenon. The production of IL-6 by MC is inhibitable by cycloheximide, thus indicating de novo synthesis. Northern blot analysis revealed a threefold increase in mRNA for IL-6 by AIgG in vitro. The increase in mRNA expression was directly related to the quantity of IL-6 released in the supernatant by MC. These results suggest that binding of AIgG or immune complexes to MC in vivo may induce IL-6 production by MC, thus leading to proliferation of MC. PMID- 8455354 TI - Differential effects of 1,25-(OH)2D3 and 22-oxacalcitriol on phosphate and calcium metabolism. AB - 1,25-dihydroxyvitamin D3 has been used with success in the treatment of secondary hyperparathyroidism associated with chronic renal failure. However, frequently 1,25-(OH)2D3 induces hypercalcemia, especially in those patients ingesting large doses of calcium carbonate, precluding the administration of therapeutic doses of 1,25-(OH)2D3. In addition, control of serum phosphorus is a persistent problem in patients maintained on chronic hemodialysis and 1,25-(OH)2D3 treatment can aggravate the hyperphosphatemia. Thus, ideally an analog of 1,25-(OH)2D3 that can suppress PTH with minor effects on calcium (Ca) and phosphate (PO4) metabolism would be an ideal tool to control secondary hyperparathyroidism. We have shown that 22-oxa-1,25-(OH)2D3 (OCT), an analog of 1,25-(OH)2D3 with little calcemic activity, can suppress PTH mRNA in normal rats and in cultured bovine parathyroid cells with equipotency to 1,25-(OH)2D3. To further characterize the differential effects of 1,25-(OH)2D3 and OCT on Ca and PO4 metabolism we performed several experiments in intact and parathyroidectomized (PTX) rats. In metabolic studies in four groups of normal rats 1,25-(OH)2D3 treatment (8 ng/day) significantly increased the intestinal Ca absorption from 15.2 +/- 2.68% to 30.5 +/- 2.85% (P < 0.01), while the same dose of OCT had no effect. A dose of 200 ng/day of OCT increased intestinal Ca absorption similarly to the 8 ng/day dose of 1,25 (OH)2D3, from 10.6 +/- 2.49% to 24.8 +/- 2.35% (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455355 TI - Intra-GBM site of the functional filtration barrier for endogenous proteins in rats. AB - The passage of various endogenous proteins [such as albumin, transferrin, immunoglobulin G (IgG), and immunoglobulin M (IgM)] across GBM was studied in vivo in normal Munich-Wistar rats. Glomeruli were fixed by three different methods: in situ drip-fixation, perfusion- and immersion-fixation; then they were processed for immunogold electron microscopy. The most reproducible results were obtained with in situ drip-fixation. Albumin, transferrin and IgG penetrated into GBM, but IgM did not. Morphometry revealed that density of albumin increased towards the inner 1/5 to 1/3 of GBM (junction of lamina rara interna and lamina densa) and decreased towards the subepithelial region of GBM, whereas density of IgG and transferrin was the highest at the subendothelial site and declined towards the subepithelial side of GBM. These findings suggest that central and/or outer zone of GBM constitute the main filtration barrier for albumin, and that subendothelial zone may contribute also to the charge-selective barrier. It is also suggested that the subendothelial zone acts more effectively as a filtration barrier for IgG and transferrin than for albumin. In the outer zone of GBM, which roughly corresponds to lamina rara externa visualized by conventional electron microscopy, the relative density of IgG and transferrin was higher than that of albumin. Since the pI of albumin was lower than that of IgG and transferrin, this finding suggests that subepithelial zone of GBM also acts as a charge-selective barrier. In conclusion, the main GBM filtration barrier for albumin might be the central and outer zones of GBM, and that for transferrin and IgG might be the entire width of GBM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455356 TI - Role of proteoglycans and cytoskeleton in the effects of TGF-beta 1 on renal proximal tubule cells. AB - Transforming growth factor-beta (TGF-beta) is a critical cell regulatory protein which influences cell growth, cell differentiation and cell chemotaxis. TGF-beta 1 has been previously shown to promote a migratory and adherent transformation of monolayers of renal proximal tubule cells in primary culture to form solid clusters of cells. To better understand the cellular basis of this TGF-beta 1 effect, these studies evaluated the influence of TGF-beta 1 on the synthesis of proteoglycans and on cytoskeleton rearrangement in rabbit renal proximal tubule cells in primary culture, and their role in this transformation effect of TGF beta 1. Biosynthetic labeling of proteoglycans with 35S sulfate and enzyme digestion studies demonstrated that TGF-beta 1 promoted the synthesis of heparan sulfate proteoglycans in these cells. The importance of proteoglycan synthesis induced by TGF-beta 1 in this migration and aggregation process was demonstrated with the use of two chemically-dissimilar proteoglycan synthesis inhibitors: xyloside and galactosamine. Both compounds inhibited TGF-beta 1 stimulation of proteoglycan synthesis and diminished TGF-beta 1 promoted transformation of proximal tubule cells as assessed by quantitative morphometry. Further experiments evaluated the influence of TGF-beta 1 on actin microfilaments with the use of rhodamine conjugated phalloidin staining and immunofluorescent microscopy, and demonstrated that TGF-beta 1 provoked a dramatic rearrangement of actin microfilaments into stress fibers. The use of actin microfilament disrupting agents, cytochalasin B and D, attenuated the stress fiber formation promoted by TGF-beta 1 and inhibited the TGF-beta 1-induced morphologic transformation of these cells. Further studies evaluated these effects on the rate of DNA synthesis in these cells, as assessed with 3H-thymidine incorporation. Proteoglycan synthesis inhibitors significantly diminished the maximal proliferative response of these epithelial cells to epidermal growth factor (EGF). In contrast, actin microfilament disaggregation with cytochalasin B or D did not change the rate of DNA synthesis in response to EGF but did attenuate the antiproliferative effect of TGF-beta 1 on EGF-induced DNA synthesis cells. These studies demonstrate that the TGF-beta 1 promoted synthesis cells. These studies demonstrate that the TGF-beta 1 promoted an increase in the production of proteoglycans and a higher ordered structure of the cytoskeleton. Both effects were instrumental in the adhesive migratory response of proximal tubule cells to TGF-beta 1 as well as the DNA synthesis rate response to both EGF and TGF-beta 1. PMID- 8455357 TI - High glucose inhibits cytosolic calcium signaling in cultured rat mesangial cells. AB - Glomerular vasodilatation in the early stages of type I diabetes mellitus apparently results from arteriolar insensitivity to vasoconstrictors. Since cytosolic free calcium ([Ca2+]i) is a major signaling mechanism for smooth muscle contraction, we studied whether growth of smooth muscle-like rat glomerular mesangial cells in media with high glucose concentration affects [Ca2+]i responses to vasoconstrictors. In cells grown for five days in 22 mM glucose, we observed blunted responsiveness to three structurally unrelated vasoconstrictors that elevate [Ca2+]i via a phospholipase C-dependent mechanism, angiotensin II, prostaglandin F2 alpha, and arginine vasopressin. Inhibition of [Ca2+]i responses was not due to an osmotic effect of high glucose, since it was not mimicked by hypertonic mannitol. While the size of intracellular Ca2+ pools was unaffected by elevated glucose, Na+/Ca2+ exchange was markedly inhibited, thus ruling out both impaired filling of Ca2+ stores and enhanced counter-regulatory mechanisms. Impaired myoinositol transport or intracellular sorbitol accumulation were not responsible for the effects of high glucose, since supplementation of media with myo-inositol or with the aldose reductase inhibitor. Alcon 1576, failed to reverse insensitivity to vasoconstrictors. On the other hand, down-regulation or pharmacological inhibition of protein kinase C completely reversed the effects of high glucose, thus indicating involvement of this signal transduction pathway. These data suggest a possible intracellular mechanism for the impaired vascular sensitivity underlying early renal hemodynamic changes in diabetes mellitus. PMID- 8455359 TI - Reversible compensatory hypertrophy in rat kidneys: morphometric characterization. AB - Functional renal compensatory hypertrophy (RCH) in the uninephrectomized rat is completely reversible by transplantation in Brown Norway (BN) rats, while anatomic RCH is not. To determine the nephron element(s) responsible for persistent anatomic RCH, we performed morphometric analysis on perfusion fixed rat kidneys following renal function studies. In this model the function of renal transplants is not different from contralateral and unmanipulated control kidneys, and there is no histological evidence of rejection. Rats uninephrectomized for three or six weeks had larger glomeruli than controls, and after transplantation of a previously hypertrophied kidney into a rat with a normal or a solitary hypertrophied kidney, glomerular size returned to control levels. Increased glomerular capillary volume (CVCP) in kidneys with RCH was due to increased capillary length (LCP; 13.1 +/- 1.0 mm cf. 10.3 +/- 0.9, P < 0.01) without increase in capillary radius (RCP; 3.26 +/- 0.33 microM cf. 3.28 +/- 0.24). In contrast, return of CVCP to control levels in kidneys undergoing regression was associated with persistently elevated LCP (13.0 +2- 2.9 mm; native previously hypertrophied kidney; 12.2 +/- 0.9; transplanted previously hypertrophied kidney vs. 10.3 +/- 0.9, P < 0.01) and decreased RCP (2.79 +/- 0.10 microM and 2.73 +/- 0.09, cf 3.28 +/- 0.24, P < 0.01). RCH was associated with proportional increases in glomerular, tubular, and vascular-interstitial volumes while only elevated tubular volume persisted during regression. Altered glomerular capillary dimensions and increased tubular volumes acquired during renal RCH induced by unilateral nephrectomy persisted during complete functional regression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455358 TI - Effect of angiotensin II and norepinephrine on early growth response genes in the rat kidney. AB - Angiotensin II (Ang II) has growth promoting effects in a number of cells and tissues in vitro. The purpose of this study was to examine the in vivo effect of Ang II on the renal expression of the early growth response genes c-fos, Egr-1 and c-jun. Adult male rats underwent two basal 30 minute clearance periods during which the normal saline vehicle was infused into the left renal artery. Normal saline, Ang II (50 ng/kg/min), or Ang II plus the Ang II antagonist Sar1 Gly8 angiotensin II (10 micrograms/kg/min) were then selectively infused into the left renal artery for two additional 30 minute periods. MAP was similar during basal and Ang II infusion. Hemodynamic effects (decrease in GFR and RPF and increase in renal vascular resistance) were observed only in the Ang II-infused left kidney allowing the right kidney to serve as a paired control for the effects of anesthesia and surgery. Significant increases in the expression of the early growth response genes Egr-1 and c-fos, but not c-jun, were found in the Ang II infused left kidney compared to the control right kidney. The simultaneous infusion of Ang II (50 ng/kg/min) and the Ang II antagonist Sar1 Gly8-angiotensin II (10 micrograms/kg/min) blocked the increase in Egr-1 and c-fos expression, demonstrating the specificity of the response to Ang II. To compare the effect of another renal vasoconstrictor on the expression of early growth response genes, norepinephrine (40 ng/kg/min) was infused into the left renal artery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455360 TI - Effect of CsA on the expression of renin and angiotensin type 1 receptor genes in the rat kidney. AB - To determine whether Cyclosporine A (CsA) alters the intrarenal expression of the renin and type 1 angiotensin II receptor genes, male adult Sprague-Dawley rats were given 25 mg/kg/day CsA s.c. for three weeks (CsA, N = 20) and were compared to pair-fed vehicle treated rats (Con, N = 20). The intrarenal distribution of renin and its mRNA was assessed by immunocytochemistry and in situ hybridization. In addition, kidney renin and type 1 angiotensin II (AT1) receptor mRNA levels were determined by Northern blot analysis. The percentage of juxtaglomerular apparatuses containing renin was higher in the CsA (84 +/- 5.5%) than in the Con (61 +/- 6.7%) group, (P < 0.05). The length of renin immunostaining along afferent arterioles was higher in the CsA (74 +/- 4.5 microns) than in the Con (37 +/- 5.1 microns) group, (P < 0.05). In contrast, neither renin mRNA levels nor its intrarenal distribution were altered by chronic CsA administration. Kidney AT1 receptor mRNA levels were lower in the CsA group than in the Con group. We conclude that chronic CsA: (1) induces recruitment of renin containing cells along the afferent arteriole, (2) causes no changes in intrarenal renin mRNA levels or distribution, suggesting that post-transcriptional events may be responsible for the persistence and/or uptake of renin by the preglomerular vasculature, (3) promotes a downregulation of AT1 receptor gene in the kidney, suggesting that local angiotensin II may control AT1 receptor gene expression by a negative feedback. PMID- 8455361 TI - Susceptibility for infection-related glomerulopathy depends on non-MHC genes. AB - BALB/c mice infected with Trypanosoma brucei and treated seven days after inoculation with Diminazene aceturate develop polyclonal B-cell stimulation, including production of antibodies to known nephritogenic autoantigens and glomerular disease associated with severe albuminuria. To investigate if the susceptibility for glomerular disease in this model is linked to MHC or non-MHC genes, we studied this disease in six mouse strains that were partly congenic for their MHC and partly congenic for their non-MHC genes. The course of the infection was measured by parasitemia and related to (auto)antibody production, proteinuria and glomerular deposition of immunoglobulins. The mouse strains could be divided into two groups. The first group consisted of the C57BL/6 (H-2b), C57BL/10 (H-2b) and B10.D2 (H-2d) strains, which proved to be relatively resistant to infection with Trypanosoma brucei (that is, spontaneous survival > 25 days). In sera of these mice antibodies to a broad range of antigens could be found 14 days after inoculation; no proteinuria was observed. The second group consisted of the BALB/c (H-2d), BALB.B (H-2b) and DBA/2 (H-2d) strains, which were relatively susceptible to the infection. In these animals proteinuria occurred and a broad polyclonal B-cell stimulation was seen 42 days after inoculation. No correlation was found between the specificity of circulating antibodies and the occurrence of proteinuria or a glomerular fluorescence pattern. These results indicate that in this model non-MHC genes govern the outcome of the infection as well as the development of polyclonal B-cell stimulation and proteinuria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455362 TI - Calcium kinetics and the long-term effects of lowering dialysate calcium concentration. AB - The optimal dialysate calcium (Ca) content for hemodialysis has been classically fixed at 1.75 mM. However, this dialysate Ca concentration (dCa) with its positive intradialytic Ca balance combined with the use of CaCO3 as a phosphate binder may result in hypercalcemia. To prevent or treat hypercalcemia, a decrease in dCa has been proposed. In the present study both the acute and the long-term effects of lowering dCa were assessed. Additionally, given the results obtained after one year with low dCa the effectiveness of i.v. 1 alpha vitamin D3 in lowering PTH serum levels in two groups of patients dialyzed with different dCa was also studied. (a) Ca kinetics during hemodialysis (HD) and on line hemodiafiltration (HDF) were studied in a group of nine stable patients who were sequentially treated with 1.75, 1.5 and 1.25 mM dCa. Dialysate was the same but for the dCa which was lowered stepwise. Na, K, tCa, ionized Ca (iCa), proteins, phosphate and pH were measured from blood inlet and outlet and dialysate outlet at the start, one hour, two hours and after the treatments. At the same time weight, blood pressure and heart rate were recorded. The sieving of iCa was significantly different in HDF versus HD (F = 6.73; P < 0.01); intravenous infusion of 18 liters of filtered ultrapure dialysate compensated the Ca loss due to the convective component of HDF, as iCa was similar at the blood inlet in HD and HDF in the three dCa tested (F = 2.59; NS). Intradialytic iCa kinetics measured in the blood inlet were significantly different with different dCa (P < 0.001 for 1.75 mM vs. 1.5 mm and P < 0.001 for 1.5 mM vs. 1.25 mM). A significant increase in post-dialysis iCa was observed with dCa of 1.75 and 1.5 while no modification was observed with 1.25 mM dCa. (b) Regarding long-term effects of lowering dCa, seven of the nine patients acutely studied were followed for a one year period after changing from dCa = 1.5 to dCa = 1.25 mM. A control group of six patients was maintained with dCa = 1.5 for the same period of time and with the same treatment schedule but for dCa. Total Ca, phosphate and alkaline phosphatase were assessed monthly, and phosphate binders and oral vitamin D derivative doses were adapted accordingly. Intact PTH was determined quarterly. CaCO3 oral intake was more than doubled in the low dCa group. Total Ca, phosphate and ALP were similar in both groups over the assessed year.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8455363 TI - Immuno-effector characteristics of peritoneal cells during CAPD treatment: a longitudinal study. AB - Peritoneal cells (PC) from 75 patients were immuno-phenotypically and functionally characterized during the first year of CAPD treatment (PCcapd) and compared to PC obtained by laparoscopy of healthy women (control peritoneal cells). Patients were divided, according to their peritonitis incidence (PI), into a high PI (HPI) and a low PI group (LPI). The yield of PCcapd decreased significantly over the year. The differential cell count and immunophenotype of PCcapd remained unchanged in the LPI group, but the percentage of macrophages decreased over the year in the HPI group. Macrophages in the PCcapd, when compared to control peritoneal cells, had a less mature phenotype as measured by RFD7 expression but a higher Fc-receptor expression. The PCcapd showed a higher percentage of B cells, CD4 positive T cells and activated T cells bearing HLA DR/DQ when compared to the control peritoneal cells. Over the year a decrease in chemotactic activity of the PCcapd towards 10(-8) M N-formylmethionyl-leucyl phenylalanine and dialysis effluent was observed in LPI patients but not in HPI patients. After one year of treatment, a significantly higher percentage of phagocytosing macrophages in the PCcapd of HPI patients was found when compared to LPI patients. During the year there was an increase of immunophagocytosis of PCcapd independent of PI. In conclusion, the CAPD peritoneal cellular immune system showed signs of both immaturity and activation. The decrease in the yield and in the chemotactic activity of PCcapd suggests an adaptation to the chronic stimulus of the dialysis fluid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455364 TI - Beta2 integrins are required for neutrophil degranulation induced by hemodialysis membranes. AB - An untoward consequence of hemodialysis is degranulation of peripheral blood neutrophils. The mechanisms that mediate this process, however, have not been conclusively identified. In the present study, the participation of complement activation and beta 2 integrins (CD11/CD18) in hemodialysis-induced neutrophil degranulation was investigated. Incubation of neutrophils with cuprophan membrane stimulated the release of very small amounts of the cytoplasmic granular protein, elastase. This release was markedly enhanced by the addition of plasma. Inactivation of complement reduced degranulation by approximately 60%, but the contribution of anaphylatoxins C3a and C5a to the degranulation process was modest. Treatment of plasma with EDTA completely abolished neutrophil degranulation in the presence of cuprophan membrane. Further, when incubated with plasma and cuprophan membrane, neutrophils that are deficient in beta 2 integrins released only 10% as much elastase as normal cells. Together, these observations strongly suggest that one or more members of the beta 2 integrin family of receptors is essential for cuprophan membrane-induced neutrophil degranulation and that both complement-related and noncomplement-related factors serve as receptor ligands. PMID- 8455365 TI - Renal interstitial expansion in insulin-dependent diabetes mellitus. AB - Eighty-four patients with insulin-dependent diabetes mellitus had studies of renal function and quantitative renal morphometry including mesangial volume fraction (Vvmes/glom), index of arteriolar hyalinosis, percentage of globally sclerosed glomeruli (%GS), and interstitial volume fraction for total renal cortex (Vvint/T). There was significant correlation among these four parameters, and all four structural parameters correlated with glomerular filtration rate and the log of urinary albumin excretion. Stepwise multiple regression analysis showed that Vvmes/glom and Vvint/T were additive, suggesting that they are partially independent. Arteriolar hyalinosis and %GS did not improve the correlations further. We hypothesize that Vvmes/glom, Vvint/T, arteriolar hyalinosis, and %GS represent multiple but probably interrelated pathologic mechanisms leading to the functional disturbances of diabetic nephropathy. Longitudinal studies of patients with diabetes and studies of patients with diseases producing interstitial expansion in the absence of glomerular disease may help clarify the independent role of interstitial expansion in the kidney disease of diabetes mellitus. PMID- 8455366 TI - Baseline analysis of renal function in the Diabetes Control and Complications Trial. The Diabetes Control and Complications Trial Research Group [corrected]. AB - To determine whether there are relationships between nephropathy, retinopathy and putative risk factors at points very early in the development of long-term complications of IDDM, we have analyzed baseline data pertinent to nephropathy in the 726 subjects in the primary prevention cohort and the 715 subjects in the secondary intervention cohort of the DCCT. AER correlated positively with CCr and HbA1c in both cohorts and with degree of retinopathy and duration of IDDM in the secondary cohort. Within the secondary cohort only mean BP and HbA1c levels were significantly increased (P < 0.005) in the 73 subjects with AER > or = 28 micrograms/24 hr compared to the 642 subjects with AER < 28 micrograms/24 hr. Stratification of all subjects in the secondary cohort showed significant associations (P < 0.001) between retinopathy level, AER, duration of diabetes at entry and entry HbA1c. Even very early in the development of retinopathy and nephropathy, there is a relationship between them and with level of metabolic control. The prospective studies of the DCCT are designed to answer the question of whether intensive diabetes treatment will affect the development and/or progression of retinopathy, and, possibly, of nephropathy. PMID- 8455367 TI - Alpha-enolase: a novel cytosolic autoantigen in ANCA positive vasculitis. AB - Anti-neutrophil cytoplasmic antibodies (ANCA) in sera from patients with clinically proven vasculitis have been described as reacting with proteins present in the granules of human neutrophils. We have studied sera from 59 ANCA positive patients to further characterize the antibody response. In addition to the antigens previously identified in the vasculitic syndromes (myeloperoxidase and serine proteinase 3) the majority of these sera contained antibodies that reacted with a cytosolic extract of neutrophils on Western blots. Nearly 40% of these sera had antibodies directed against a cytosolic protein(s) of molecular mass 48 kD. This protein was purified from neutrophil cytosol by ammonium sulphate fractionation, anion exchange and reverse phase chromatography. Amino acid sequence analysis of a proteolytic fragment of this protein identified it as alpha enolase. The anti-enolase antibodies only recognized the alpha isoform and were present in sera giving either a pANCA or cANCA staining pattern by indirect immunofluorescence. Antibodies to alpha enolase were also found in sera from patients with systemic lupus erythematosus, particularly those with renal disease. We conclude that the antibody response in ANCA positive vasculitis is not restricted to neutrophil granule proteins. PMID- 8455369 TI - Hyperparathyroidism, platelet intracellular free calcium and hypertension in chronic renal failure. AB - To investigate possible relationships between hyperparathyroidism, alterations in intracellular free calcium concentration ([Ca2+]i) and hypertension in chronic renal failure, serum concentrations of intact parathyroid hormone (PTH) were measured by two-site immunometric assay, and platelet ([Ca2+]i) was assessed using the fluorescent indicator fura-2. Thirty-six patients with chronic renal failure were studied, 10 with normal serum PTH concentrations (mean 8.0 +/- 0.6 pmol/liter), 17 with elevated serum PTH (35.0 +/- 7.2 pmol/liter) and 9 patients with elevated PTH (36.2 +/- 5.9 pmol/liter) who were receiving nifedipine. Platelet [Ca2+]i was increased in patients with elevated PTH, compared with those in whom PTH was normal (138 +/- 16 vs. 83 +/- 7 nmol/liter, P < 0.01). A linear relation was observed between serum PTH and platelet [Ca2+]i in these patients (r = 0.818, P < 0.001). In contrast, platelet [Ca2+]i was not elevated (84 +/- 9 nmol/liter) in the patients with elevated PTH who were receiving nifedipine. A linear relation was also present between both serum PTH (r = 0.616, P < 0.001) and platelet [Ca2+]i (r = 0.576, P < 0.005) and mean blood pressure. Nine patients with hyperparathyroidism were restudied after treatment with the vitamin D analogue alfacalcidol. This resulted in significant decreases in serum PTH (P < 0.01), platelet [Ca2+]i (P < 0.02), and mean blood pressure (P < 0.05). These studies indicate that [Ca2+]i may be increased early in renal failure, and that this increase occurs in association with both hyperparathyroidism and hypertension. Furthermore, treatment of hyperparathyroidism with alfacalcidol may result in reductions in both [Ca2+]i and blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455368 TI - In situ production of TNF-alpha, IL-1 beta and IL-2R in ANCA-positive glomerulonephritis. AB - Humoral and cellular immune mechanisms are thought to be involved in various forms of vasculitis and glomerulonephritis. Recent clinical and experimental results point to a role of cytokines in ANCA-positive vasculitides. We analyzed tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-2 receptors (IL-2R) in renal biopsies and in plasma from 22 patients with Wegener's granulomatosis and microscopic polyangiitis. Kidney biopsies were examined by immunocytochemistry, polymerase chain reaction and in situ hybridization. Immunoreactive TNF-alpha, IL-1 beta and/or IL-2R positive infiltrating cells were observed in 21 of 22 biopsies. TNF-alpha, IL-1 beta and IL-2R staining was evident in the interstitium and at periglomerular and perivascular sites. The number of positive cells was markedly increased in biopsies with active lesions. Positive cells were also present in cellular and fibrocellular crescents, surrounding tuft necrosis and in the walls of arteries and arterioles with acute vasculitic lesion. Some tubular epithelial cells stained for TNF-alpha and IL-1 beta. TNF-alpha, IL-1 beta and IL-2R positive infiltrating cells correlated with the presence of histologically active renal lesions. The evaluation of TNF-alpha and IL-1 beta expression at the mRNA level assessed by the polymerase chain reaction demonstrated specific transcripts for TNF-alpha and IL-1 beta in all six cases analyzed. In situ hybridization studies showed an increased expression of mRNA for TNF-alpha and IL-1 beta in infiltrating mononuclear cells, in epithelial cells of Bowman's capsule and in some tubules, predominantly of patients with active renal lesions. The results at the mRNA level correlated with the immunocytochemical findings. Compared to healthy individuals higher TNF-alpha plasma levels were observed in patients with vasculitis (34.4 +/- 16.6 pg/ml (SEM) vs. 1.9 +/- 0.7 pg/ml in controls; P < 0.01). All patients presented a marked increase in sIL-2R plasma levels (3512 +/- 485 U/ml vs. 397 +/- 21 U/ml in healthy controls; P < 0.001). IL-1 beta was not detected in most plasma samples. Elevated TNF-alpha and sIL-2R plasma levels were related to active renal lesions. Our study clearly demonstrates that in ANCA positive vasculitis TNF-alpha and IL-1 beta are produced in situ by activated infiltrating mononuclear cells and resident renal cells. Intrarenal localization of cytokine producing cells and the correlation between cytokine production and histological signs of activity suggest that TNF-alpha and IL-1 beta are important locally acting mediators in the vasculitic/glomerulonephritic process. PMID- 8455370 TI - Calcium channel blockers protect transplant patients from cyclosporine-induced daily renal hypoperfusion. AB - Renal toxicity, possibly due to vasoconstriction and vascular injury, is the most relevant side-effect of chronic cyclosporine (CsA) therapy given to prevent graft rejection. In kidney transplant recipients each oral dose of CsA is invariably followed by a transient reduction in renal plasma flow (RPF) and glomerular filtration rate (GFR) that results from a form of acute reversible hypoperfusion. We sought to determine whether the Ca2+ channel blocker, lacidipine, prevented CsA-associated renal hypoperfusion in these patients. Parallel studies on CsA pharmacokinetics, renal function parameters (GFR and RPF), as inulin and p aminohippurate (PAH) clearances, respectively, and urinary excretion of the vasoconstrictor endothelin in 10 consecutive renal transplant patients given CsA as a part of their immunosuppressive therapy were performed. Patients were studied at different time intervals after CsA alone, CsA and lacidipine (4 mg/day), and again seven days after lacidipine withdrawal. In all patients basal RPF and GFR declined on average 51% (139.3 +/- 20.7 ml/min/1.73 m2) and 50% (32.5 +/- 5.8 ml/min/1.73 m2), respectively, two to four hours after maximum blood CsA concentration was reached. As blood levels of CsA returned to trough, both parameters progressively increased to baseline. Lacidipine administration completely prevented the fall in RPF (pre-CsA: 277.1 +/- 23.6; 6 hr post-CsA: 304.5 +/- 31.1 ml/min/1.73 m2) and GFR (pre-CsA: 66.6 +/- 8.1; 6 hr post-CsA: 70.1 +/- 9.8 ml/min/1.73 m2). When lacidipine treatment was discontinued the abnormal RPF and GFR response to CsA administration was again observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455371 TI - Gene expression of interleukin-1 beta during hemodialysis. AB - It is still controversial whether the hemodialysis (HD) procedure is an inflammatory process in vivo. Therefore, we studied the gene expression of interleukin-1 beta (IL-1 beta) as a marker of inflammation in peripheral blood mononuclear cells (PBMC) of patients during HD by Northern blotting and polymerase chain reaction. Compared to PBMC separated pre-HD (1.0 densitometric units), the amount of IL-1 beta mRNA was increased in PBMC leaving the dialyzer (12.2 +/- 2 densitometric units, P < 0.01), but was not increased in PBMC re entering the dialyzer from the systemic circulation (0.6 +/- 0.1 densitometric units) in all 12 patients studied. The maximal amount of IL-1 beta mRNA in PBMC was seen at five minutes after start of HD. There was a significant correlation between the increase in IL-1 beta mRNA and the increase in activated complement C5a (r = 0.71, P < 0.01). HD using less complement-activating membranes (hemophan, polysulfone, polyamide or polyacrylonitrile) resulted in no detectable IL-1 beta mRNA. Furthermore, a monoclonal antibody against human C5a reduced the increase in IL-1 beta mRNA by 83% (P < 0.05), indicating that C5a plays a major role for induction of IL-1 beta mRNA during HD. This study demonstrates that during HD with regenerated cellulose, gene expression for IL-1 beta takes place in PBMC. PMID- 8455373 TI - Isolation and characterization of complement receptor type 1 from rat glomerular epithelial cells. AB - Complement receptor type 1 (C3b/C4b receptor, CR1) is known to be present in human glomerular epithelial cells (GEC) in vivo. The presence of CR1 has not been documented in rat glomeruli, although cultured rat GEC appear to express CR1 based upon their ability to rosette with complement-coated erythrocytes. In this study, we establish that CR1 is present in cultured rat GEC: (1) by isolating a 200 kDa protein from detergent-solubilized cultured rat GEC through the use of C3b affinity chromatography; (2) by Western blotting studies demonstrating reactivity of anti-human CR1 antibodies with this protein from cultured GEC; and (3) by demonstrating that C3b binding to GEC monolayers exhibits low affinity and that an estimate of the number of binding sites is 6700 per cell, both of which are comparable to that seen for CR1 in human blood cells. Furthermore, we show that CR1 is also present in rat glomeruli by Western blotting studies with anti human CR1. Anti-human CR1 also identifies a 70 kDa protein from cultured GEC and isolated glomeruli. This 70 kDa protein is likely to be the CR1-like protein, designated Crry, which was initially identified in the mouse and has significant homology to human CR1. Crry may be present in rat GEC instead of decay accelerating factor, which is present in human GEC. PMID- 8455372 TI - Mutations in the codon for a conserved arginine-1563 in the COL4A5 collagen gene in Alport syndrome. AB - We have screened 110 unrelated Alport syndrome kindreds for mutations in the exon 48 region of the COL4A5 collagen gene. Denaturing gradient gel electrophoresis (DGGE) of the PCR-amplified region of exon 48 revealed sequence variants in DNA from affected males and carriers of three unrelated kindreds. All three kindreds have classical Alport syndrome of the juvenile type. DNA-sequencing analyses demonstrated two different single base changes in the codon for arginine-1563 located in exon 48. In Utah kindred 2103, there was a substitution of C by T resulting in the change of the CGA codon for arginine to the translation stop codon TGA. In Utah kindred 2123 and in the Danish kindred A13, there was a C-->T mutation in the noncoding strand changing the same codon to CAA for glutamine. Both mutations were confirmed by allele-specific hybridization on PCR-amplified DNA from other family members. PMID- 8455374 TI - Hepatorenal syndrome. PMID- 8455376 TI - Distal esophageal rupture following blunt trauma. PMID- 8455375 TI - And now for the rest of the story. PMID- 8455377 TI - A patient with congestive heart failure. PMID- 8455378 TI - A patient with fever and pain. PMID- 8455379 TI - Assessment and care coordination teams: an innovation in caring for children. PMID- 8455380 TI - Headache--an important symptom. PMID- 8455381 TI - Radiology case of the month. Paraganglioma. PMID- 8455382 TI - CARE program targets media and legislators as part of health care information campaign. TMA Communications and Public Service Committee. PMID- 8455383 TI - Loss prevention. PMID- 8455384 TI - Permanent resolution of severe second trimester oligohydramnios after transabdominal amnioinfusion. PMID- 8455385 TI - Hemolytic disease of the newborn due to anti-c. PMID- 8455386 TI - Health care reform in Kentucky--who, what, when, why and how? PMID- 8455387 TI - Ethics Committee report: American Nurses Association position statement on HIV infection and nursing students. PMID- 8455388 TI - 120th anniversary of St. Luke's Hospital. PMID- 8455389 TI - Tissue-integrated dental prostheses: the first 78 months of experience at the Mayo Clinic. AB - During a 78-month period at the Mayo Clinic, 1,778 Branemark endosseous dental implants were placed in the edentulous or partially edentulous jaws of 353 consecutive patients who ranged in age from 8 to 82 years. The largest treatment category involved edentulous mandibles, which accounted for 53% of the total restorations. Approximately 76% of the threaded cylindrical implants supported 312 oral prostheses at the end of the study period. The implant survival rate was 97.8% in the mandible and 88.8% in the maxilla. Complications associated with this treatment included loss of implant anchorage in bone, soft tissue problems, and mechanical difficulties related to design and function of the prostheses. All complications were managed without loss of continuous function of the prostheses, except in four patients who resumed wearing a conventional removable maxillary complete denture. This experience demonstrates that Branemark endosseous dental implants are predictable and can provide lasting integration under function when placed and loaded in accordance with the recommended protocol. PMID- 8455390 TI - Cessation of unsuccessful pediatric resuscitation--how long is too long? AB - Emergency teams asked to provide cardiopulmonary resuscitation for pediatric patients often consist of nurses and physicians from various pediatric and nonpediatric specialties. Team members should agree on the timing of termination of unsuccessful resuscitative efforts; however, no firm guidelines about such timing have been established. The purposes of this study were to determine (1) whether a consensus exists among health-care professionals about the optimal duration of unsuccessful resuscitation for pediatric patients and (2) whether attitudes are influenced by individual case prognosis, medical specialty, level of training, or certification in pediatric advanced life support (PALS). By random selection, 140 physicians, nurses, and medical students were asked to specify the duration that they would continue unsuccessful resuscitative efforts for each of two hypothetical cases: one patient with a good prognosis for survival and one with a poor prognosis. Although no clear consensus existed, all groups of health-care providers chose significantly briefer durations of resuscitation for the case with a poorer prognosis (P < 0.01). The specified durations of resuscitation were briefer for those who had PALS certification than for those who did not and for pediatricians than for nonpediatric physicians (P < 0.01). Furthermore, PALS certification (P < 0.01) and pediatric specialty (P < 0.05) contributed as independent variables in influencing the study participants' attitudes about duration of resuscitation, whereas level of training did not. We conclude that no consensus exists among the groups studied on the optimal duration of unsuccessful resuscitative efforts in pediatric patients. We speculate that the opinions might be more uniform if resuscitation of pediatric patients was provided primarily by pediatricians or PALS-certified physicians. PMID- 8455391 TI - Carotid endarterectomy in patients with contralateral carotid occlusion. AB - In this study, we assessed the results of carotid endarterectomy in 357 patients with a carotid stenosis and contralateral carotid occlusion. The overall major neurologic morbidity was 0.6%, and the minor morbidity was 1.1%. The causes of four perioperative deaths (1.1%) were myocardial infarction in two patients, ruptured abdominal aortic aneurysm in one, and respiratory complications in one. Therefore, an excellent result was achieved in 97.2% of patients. With occlusion of the carotid artery for the endarterectomy, 165 patients (46%) had appreciable attenuation in intraoperative electroencephalographic findings and a decrease in cerebral blood flow to approximately 10 ml/100 g of brain tissue per min that necessitated placement of a shunt. This high percentage of profound electroencephalographic and blood flow changes during carotid occlusion suggests that the potential for collateral blood flow in this group of patients is minimal. These results demonstrate that a carotid endarterectomy can be performed at low risk in patients with a contralateral carotid occlusion. We advocate annual noninvasive carotid testing for patients with asymptomatic carotid stenosis and contralateral carotid occlusion. If progression of the stenosis is evident, a prophylactic endarterectomy should be considered because these patients may have a higher risk for cerebral infarction than do patients with a unilateral asymptomatic stenosis. PMID- 8455392 TI - "Suspicious" thyroid cytologic findings: outcome in patients without immediate surgical treatment. AB - From January 1980 through December 1988, 8,219 thyroid smears were obtained by fine-needle aspiration (FNA) biopsy from patients at the Mayo Clinic, of which 918 (11%) were classified as "suspicious" cytologic findings. We analyzed the outcome in 208 patients with such findings who did not undergo immediate surgical treatment at the Mayo Clinic; follow-up data on thyroid status were available for 187 patients. Of 99 patients who underwent late surgical treatment (more than 30 days after FNA biopsy) and for whom tissue was available for diagnosis, thyroid malignant disease was found in 29. No clinical, scintigraphic, or ultrasonographic characteristics predicted the presence of a malignant lesion. On repeated FNA biopsy in 41 patients, findings were suspicious for a malignant lesion in 19 and benign in 22. Surgical excision was performed in 13 of the 41 patients. For 11 patients with suspicious cytologic findings on two FNA biopsies, malignant disease was confirmed in 5 and benign disease in 6. Two patients had benign histopathologic findings after cytologic results were benign on a second FNA biopsy. Follow-up data for the 208 patients revealed that 86 were alive with no evidence of thyroid disease, 76 were alive with some evidence of thyroid disease, 23 had died of nonthyroid illnesses, 2 had died of a thyroid malignant lesion, and 6 had died without undergoing surgical treatment (thyroid status unknown at the time of death); follow-up information was unavailable in 15 patients. The median duration of follow-up for those alive was 4.9 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455393 TI - Chronic diarrhea due to surreptitious use of bisacodyl: case reports and methods for detection. AB - Surreptitious abuse of laxatives is a common cause of severe chronic diarrhea. Standard laboratory screening studies of urine and stool specimens may identify phenolphthalein, diuretics, and magnesium-containing agents. An assay for bisacodyl, a commonly used over-the-counter laxative, however, is not included in routine screening tests. Herein we describe two patients with chronic watery diarrhea of large volume; analysis of stool and urine samples revealed that surreptitious use of bisacodyl was the cause. In one patient, nonspecific inflammatory changes of the colonic mucosa were noted on biopsy, and fecal leukocytes were detected in both patients. In a prospective study of eight patients who received bisacodyl as part of a preparation for colonoscopy, we analyzed serial urine samples for bisacodyl diphenol during a 48-hour period. This metabolite was found in seven of eight hydrolyzed urine samples obtained 12 hours after oral administration of bisacodyl but not in samples obtained 24 and 48 hours after ingestion of the laxative. We recommend that urinalysis and, in some cases, stool analysis for bisacodyl should be considered in the diagnostic assessment for surreptitious use of laxatives. PMID- 8455394 TI - Hyperlipoproteinemia in adults with renal disease. AB - Hyperlipoproteinemia is common in patients with renal disease, but increased lipids are only one of several risk factors frequently identified for coronary artery disease. Before treatment options are instituted, renal disease status, current medications, and possible interactions between drugs must be considered. Hypertriglyceridemia is common in patients with renal failure; therapeutic options are influenced by the levels of serum triglycerides and high-density lipoprotein cholesterol. If nonsteroidal drugs improve renal function and decrease proteinuria in patients with renal disease, hyperlipidemia frequently abates. Interactions between drugs are important considerations when lipid lowering drug treatment is prescribed in recipients of renal transplants. PMID- 8455395 TI - Multifocal leukoencephalopathy: occurrence during 5-fluorouracil and levamisole therapy and resolution after discontinuation of chemotherapy. AB - We report the fourth case of cerebral demyelinating disease associated with 5 fluorouracil and levamisole hydrochloride therapy for adenocarcinoma of the colon. The initial manifestations included subacute progressive decline in mental status, ataxia, dysarthria, and diplopia. Magnetic resonance imaging of the head demonstrated multifocal enhanced lesions in the white matter. The patient experienced improvement, without corticosteroid treatment, from 2 weeks to 4 months after cessation of chemotherapy. PMID- 8455396 TI - Carotid sinus syndrome and wrestling. AB - A 17-year-old boy who lost consciousness during wrestling matches was found to have carotid sinus syndrome. To our knowledge, this report is only the second published case of this entity in an adolescent. Herein we discuss possible implications of this finding for the assessment of syncope in pediatric patients. PMID- 8455397 TI - Nikola Tesla--pioneer of modern electrical power. PMID- 8455398 TI - Preoperative pulmonary function testing for patients with lung cancer. AB - Preoperative functional assessment of patients who are scheduled to undergo pulmonary resection for carcinoma of the lung can assist the clinician in determining perioperative risk. Physiologic alterations that occur after thoracotomy, including changes in lung volume, ventilatory pattern, gas exchange, and respiratory defense mechanisms, impose an increased risk of complications in patients with moderate to severe respiratory impairment. The use and shortcomings of preoperative spirometry and arterial blood gas analysis as predictors of perioperative complications are reviewed. Quantitative radionuclide scintigraphy, and in some cases exercise testing, can further determine the operative risk of patients with lung cancer. For patients with increased risk, implementation of prophylactic measures may decrease postoperative complications. PMID- 8455399 TI - Approach to the solitary pulmonary nodule. AB - Because many malignant and benign processes may manifest as a solitary pulmonary nodule on a chest roentgenogram, this finding presents a diagnostic challenge. The major concern is whether the lesion is malignant. The likelihood of a malignant tumor correlates with the age of the patient, the size of the nodule, a history of a prior malignant lesion, and a history of smoking. Recent advances in radiologic techniques, such as the detection of calcium or the inference of the presence of calcium by high attenuation values on computed tomography, provide assistance in identifying benign lesions. The history, physical examination, and radiographic information can help determine an appropriate course of action. The goals are to remove malignant nodules promptly and to avoid surgical intervention in patients whose nodules are benign. PMID- 8455400 TI - Bronchogenic carcinoma: immunologic aspects. AB - Evidence that host immunologic function may influence the behavior of lung cancer is accumulating. Non-small-cell lung cancers are heavily infiltrated by host lymphocytes. The fact that monoclonal antibodies have been developed against lung cancer cells implies that such cells express surface antigens and are therefore vulnerable to immune recognition. Failure of the host defense mechanism to control tumor growth may involve (1) reduced natural killer cell activity, (2) inadequate lymphokine-activated killer cell function, or (3) tumor secretion of immunomodulating factors. Basic immunologic research studies of lung cancer are increasing the potential for clinical applications. New monoclonal antibodies have improved both the sensitivity and the specificity of immunohistopathologic analyses of pulmonary specimens. Links between immune function and prognosis in patients with lung cancer have been established. Finally, initial results from protocols that have used tumor-infiltrating lymphocytes, interleukin 2, and tumor vaccines suggest that immunobiologic treatment modalities may be increasingly applicable in patients with lung cancer. PMID- 8455401 TI - Case of the month. Urachal carcinoma. PMID- 8455402 TI - The blindness of John Milton. AB - John Milton (1608-1674) has often been regarded as the greatest poet of his time, yet he did not compose his most famous work, Paradise Lost, until after he had become blind in both eyes. On the basis of clues in Milton's writings, several possible diagnoses have been advanced to explain his loss of vision. Herein the evidence for and against each theory is presented. PMID- 8455403 TI - Ghosts from Samaria: Good Samaritan laws in the hospital. AB - Each state has one or more statutes that collectively can be termed "Good Samaritan" laws. Such laws purport to protect physicians and others who volunteer assistance during emergencies. The application of Good Samaritan laws to physicians within a hospital is uncertain and varies from state to state and case to case. No sure way exists to predict whether Good Samaritan laws will protect physicians assisting patients in apparent emergencies. Physicians should not act in reliance on such laws but rather on personal considerations when they volunteer during emergencies. An Illinois case in which a Good Samaritan law was successfully used as a defense illustrates the many variables that make predictions about such laws doubtful. PMID- 8455404 TI - Osseointegrated dental implants--another option in clinical dentistry. PMID- 8455405 TI - The decision to halt a pediatric resuscitation. PMID- 8455406 TI - Gestational diabetes mellitus. PMID- 8455407 TI - Restenosis comes of age. PMID- 8455408 TI - [Contact urticaria and latex anaphylaxis. A review of 15 cases]. AB - BACKGROUND: Since the recent description of immediate hypersensitivity to latex, many cases have been reported, some of them with anaphylactic reactions. The aim of this study is to analyze the clinical findings, diagnostic management and therapeutic procedures in these patients. METHODS: We reviewed the clinical findings in 15 patients with contact urticaria to latex from our files. Use-test with a surgical glove, prick-test trough a rubber glove, RAST to latex and standard patch-tests were performed in each case. RESULTS: We found a M:F ratio of 1:4 (3 males and 12 females) and the mean age at diagnosis was 33 years. Atopic background was present in 60% of cases and 46% were health care workers. Systemic manifestations of allergy were found in 25% of patients. Two cases developed anaphylactic shock. Cutaneous manifestations included localized contact urticaria in 33% of cases, chronic hand eczema and urticaria in 46%, and immediate contact dermatitis in 20%. All cases showed a positive use-test, while prick-test and RAST showed positive results in only 75% of patients. Positive patch-test to rubber accelerators were found in 33% of cases. CONCLUSIONS: Latex immediate hypersensitivity is frequently seen at present. Its prevalence in health care workers is high. Atopic constitution, chronic hand eczema, continuous gloves usage, and contact dermatitis to rubber additives are predisposing factors. Diagnosis can be assessed by clinical findings and use-test, confirming by prick-test and RAST. PMID- 8455409 TI - [Endocarditis due to penicillin-sensitive and -resistant pneumococci: the current perspectives on the disease]. AB - BACKGROUND: To evaluate the clinic characteristics and therapeutic aspects of endocarditis by Streptococcus pneumoniae sensitive and resistant to penicillin. METHODS: Twelve cases of pneumococcal endocarditis evaluated in 4 Spanish hospitals over the last 10 years were studied, analyzing their clinical characteristics and the existence of resistance to penicillin. The features were compared with a series of 98 cases found in a review of the literature. RESULTS: All the patients were males, most being alcoholics. The course of the disease was acute (2 weeks) in all the cases and evolved with great aggressivity: cardiac failure (9 patients), myocardial abscess (7 patients), multiple arterial embolisms (5 patients), septic arthritis (4 patients). Three patients had simultaneous pneumococcal meningitis but only one had pneumonia. The valve most affected was the aortic (9 cases). Three cases were due to strains of Streptococcus pneumoniae with moderate resistance to penicillin (CMI 0.5-1 micrograms/ml). Global mortality was 42%. All the patients receiving inadequate antibiotic treatment died. Vancomycin and cefotaxime appear to be effective in the treatment of cases produced by strains of pneumococcus with intermediate sensitivity to penicillin. There were no apparent differences in mortality between the cases of endocarditis by pneumococcus sensitive or moderately resistant to penicillin. CONCLUSIONS: Pneumococcal endocarditis continues to condition a high mortality similar to that produced in previously made series. The classic relation with meningitis and pneumonia is infrequent today. The appearance of strains resistant to penicillin may increase the incidence of this infection and further worsen prognosis. PMID- 8455410 TI - [The estimation of the cost of nosocomial infection in an intensive care unit]. AB - BACKGROUND: Nosocomial infection (NI) represents an increase of hospital morbidity and mortality. The data available concerning the hospital expenses due to the prolongation of hospital stay associated to NI are fundamentally derived from American studies. The aim of this study was to evaluate the direct cost of nosocomial infection in an intensive medicine unit (IMU). METHODS: A study of cases and paired controls was carried out with a cohort study made up of 88 cases and 88 controls paired by age and severity (APACHE II grading). Previously identified confusion factors were controlled in the analysis. RESULTS: The mean stay in the IMU for infected patients was 17.2 days and for non infected patients 6.8 days. When these stays were adjusted by the variables associated with both NI and in the IMU this became 14.2 days for infected patients and 9.9 days for uninfected patients. The prolongation of stay in the IMU due to NI was 4.3 days. The extra cost for the hospital due to infection acquired by a patient's during stay in the IMU was estimated as 239,441 pesetas. CONCLUSIONS: The methodology used was considered as valid for estimating the prolongation of stay in intensive medicine units attributed to nosocomial infection. The high economic expense which nosocomial infection represents emphasizes the justification for measures of control of this entity. PMID- 8455411 TI - [Between the clinical trial and clinical ethics: good clinical practices]. PMID- 8455412 TI - [Exhaustion syndromes in a popular marathon]. AB - The clinical characteristics of seven healthy subjects who required hospital care for an exhaustion syndrome due to extenuated physical exercise during participation in a public marathon are presented. All the patients were used to practising sports activities and in all the cases the symptoms of exhaustion appeared in the last few kilometers of the race. The most frequent symptom found in all the patients was lipothymia with falling to the ground followed by gastrointestinal manifestations, muscle cramping and fever. Upon analysis the signs of rhabdomyolysis and others suggestive of dehydration were observed in all the cases. Leukocytosis was observed in four and hypopotassemia in two. Evolution was good in all the cases with rest and hydroelectrolytic reposition. Finally, the preventive measures to avoid heat stroke and exhaustion syndromes in public marathons are reported. PMID- 8455413 TI - [Good clinical practices in clinical trials: the responsibility of the researcher. A survey of 827 hospital physicians (I). Availability. Monitoring. Safety. Contract]. AB - BACKGROUND: The Law of Medicaments establishes that clinical trials (CT) with drugs must be carried out following the of Good Clinical Practice guidelines (GCP). The attitude of hospital physicians to the GCP prior to its implementation as mandatory in accordance with Spanish legislation was considered to be of interest. METHODS: An anonymous survey was used with closed response questions. Questions referring to the responsibilities of the investigator included in the GCP were included. From December 1988 to February 1990 the survey was distributed among 1,706 hospital medical staff members, of any specialty, who had or had not participated in CT. In this article the results of the questions regarding the availability of the investigative team, CT monitorization, management of adverse reactions, the safety of the participants in the CT and the contract between the sponsor and the researcher are presented. RESULTS: A total of 827 hospital doctors replied to the survey. Fifty-nine percent had intervened in CT with drugs. At least 94% of those surveyed considered that the researcher must have the time and number of eligible patients which the CT requires. There was high acceptance (> or = 78%) of the clinical audits to be performed by the health authorities and the sponsor company of the CT. The need of urgent communication of the severe adverse reactions is admitted by a great majority (> or = 95%) of those surveyed. Eighty-five percent believe that patients should be insured against damage derived from CT with 76% considering that the investigator should sign a contract with the sponsor; 68% and 59% would hand in a copy of the same to the CT committee and the remainder of the research team, respectively. CONCLUSIONS: According to the Good Clinical Practice dealt with in this article, the responsibilities of the investigator have been widely accepted by the hospital physicians surveyed, therefore no problems should be expected upon the implementation of the same in this country. However, the economic transparency in the clinical trial does not appear to be absolutely necessary by the doctors surveyed. PMID- 8455415 TI - [The Minotaur syndrome]. PMID- 8455414 TI - [The effects of presurgical stress on leukocyte subpopulations]. PMID- 8455416 TI - [Almitrine bismesylate in chronic obstructive pulmonary disease]. PMID- 8455417 TI - [A health care chain for modern scientific medicine]. PMID- 8455418 TI - [Anticardiolipin antibodies in patients infected with the human immunodeficiency virus type 1]. PMID- 8455419 TI - [Anticardiolipin antibodies in patients infected with the human immunodeficiency virus type 1]. PMID- 8455420 TI - [Lipomatous hypertrophy of the interauricular septum and cardiac arrhythmias]. PMID- 8455421 TI - Treatment of decompensated viral hepatitis B-induced cirrhosis with low doses of interferon alpha. AB - Seven patients with decompensated posthepatitis B cirrhosis were treated with low doses of interferon alpha. The initial plasma level of HBV-DNA ranged from 3.0 to 189.3 pg/ml, and that of ALT from 37 to 156 IU/l. Liver biopsies demonstrated ongoing piecemeal necrosis. In sera of all but one patient, HBV-DNA became undetectable by hybridisation techniques within 10 to 28 weeks. Plasma HBeAg became negative in four and HBe-antibodies positive in three patients. Serum transaminase levels showed a marked initial rise 3 to 13 weeks after onset of therapy; they dropped to normal values later in all except one patient. Therapy was initiated at 1 MU (million units) three times a week for 2 weeks and was increased to 2.5 MU for 16 weeks. Later, this dosage was raised to 5 MU three times a week in some patients. Complications included variceal haemorrhage, aggravation of ascites or of encephalopathy, development of pneumonia, recurrence of spontaneous bacterial peritonitis or of gastric ulcer bleeding. One year after stopping the therapy, three patients are well and without any feature of liver decompensation. Three patients died before they could undergo a liver transplantation. In one patient treatment was interrupted because of marked exacerbation of liver cell necrosis. It thus seems possible to suppress HBeAg and HBV-DNA in patients with decompensated cirrhosis. This is important to prepare them for possible liver transplantation. Interferon should be initiated at low doses and the patients be very carefully monitored. Prophylactic therapy for bacterial peritonitis and for variceal haemorrhage is warranted. PMID- 8455422 TI - Arterial and mixed venous acid-base status in patients with cirrhosis. Influence of liver failure. AB - Although it has been established that liver failure is associated with arterial hypocapnia and alkalaemia (i.e., respiratory alkalosis), the influence of liver failure on mixed venous acid-base status has not yet been studied. Thus, arterial and mixed venous acid-base status were simultaneously measured in controls and in a large series of patients with cirrhosis. Grade B patients (n = 28) or Grade C patients (n = 21) had significantly lower arterial and mixed venous carbon dioxide tensions than controls (n = 29). Grade B or Grade C patients also had significantly higher arterial, mixed venous pH, and lower mixed venous bicarbonate concentrations than controls. Among Grade A patients (n = 27), those with the lowest Pugh's score (i.e., equal to five) had significantly lower mixed venous carbon dioxide tension than controls. The other arterial and mixed venous acid-base values did not differ significantly between Grade A patients with the lowest Pugh's score and controls. Grade A patients with a Pugh's score equal to six and Grade B patients had similar acid-base disorders. No significant differences were found between groups concerning the anion gap and plasma chloride concentrations. In conclusion, this study shows that in Grade B or C patients, respiratory alkalosis was responsible for mixed venous hypocapnia, alkalaemia and hypobicarbonataemia. In addition, in Grade A patients with the lowest Pugh's score (equal to five), analysis of arterial and mixed venous blood revealed that mixed venous hypocapnia was the sole anomaly of the acid-base status. This last finding suggests that mixed venous hypocapnia might be an early event preceding the onset of arterial hypocapnia. PMID- 8455423 TI - Hepatic arterial and portal venous oxygen content and extraction in liver cirrhosis. AB - We examined the oxygen content in the hepatic arterial, hepatic venous and portal venous blood to evaluate the oxygen supply to the liver and hepatic oxygen extraction in cirrhosis. The arterial-portal venous difference of the oxygen content was within the normal range in cirrhosis patients, although the oxygen content of the hepatic artery and portal vein was lower than in the control patients. The hepatic venous oxygen content was normal in the cirrhosis patients. The oxygen tension and saturation were always higher in the splenic vein than in the other branches of the portal system. Oxygen was supplied chiefly by the hepatic artery, and arterial oxygen extraction was normal in cirrhosis. In addition, there was no change in arterial extraction during oxygen inhalation by cirrhosis patients. Portal venous oxygen extraction was decreased in cirrhosis and was increased by oxygen inhalation. These findings indicate the autoregulation of hepatic oxygen through a mutual relationship between the hepatic arterial and the portovenous oxygen supply. PMID- 8455424 TI - Effects of prednisolone pretreatment in interferon alfa therapy for patients with chronic non-A, non-B (C) hepatitis. AB - The effect of corticosteroid pretreatment on interferon alfa treatment of chronic non-A, non-B or C hepatitis was evaluated in an open, randomized, controlled study. Normalization of the serum alanine aminotransferase level, which suggested complete response, was recorded in 14 (56%) of 25 patients at the end of a 6 month treatment with 3 million units of interferon alfa three times weekly alone. Prednisolone withdrawal followed by the same interferon alfa treatment resulted in complete response in 14 (61%) of another 23 patients. Both of these rates are significantly higher than the spontaneous ALT normalization rate of 9% observed in 2 of 22 patients during the same period (p < 0.01). ALT normalized within 2 months of interferon therapy in most (89%) of the complete responders. Of the patients pretreated with prednisolone, 43% showed a "rebound" following prednisolone withdrawal and 89% of the patients with "rebound" responded to subsequent interferon therapy. The cumulative probability of sustained remission in patients with and without prednisolone pretreatment in a 24-month period of follow-up after the end of therapy was 79% and 30%, respectively (p < 0.05). Clinical relapse mostly (85%) occurred within 3 months after the end of therapy. No obvious factor could be identified as a predictor of response or relapse. The results of this study suggest that prednisolone withdrawal tends to enhance the durability of the beneficial effects of interferon alfa therapy in patients with chronic non-A, non-B or C hepatitis. PMID- 8455425 TI - Smallest angiomyolipoma of the liver in the oldest patient. PMID- 8455426 TI - MR imaging of foot and ankle tumors. AB - Twenty-one patients were referred for MR imaging of mass lesions in the foot and ankle detected initially by either palpation (15 patients) or radiographs (6 patients). In 3 cases, MRI excluded a discrete mass. In the remaining 18 patients with confirmation of mass lesions, the combination of signal features and tumor location suggested a specific diagnosis in 11 patients (61%). In 4 other cases, correlation with radiographs suggested likely diagnoses. In 3 cases, the MRI appearance was nonspecific. We conclude that the combination of signal features and tumor location at MR imaging often permits characterization of tumors of the foot and ankle. PMID- 8455427 TI - Functional anatomy of the soft tissues of the hand and wrist: in vivo excursion measurement of the flexor pollicis longus-tendon using MRI. AB - Magnetic resonance imaging (MRI) of the flexor pollicis longus-tendon (FPL tendon) with the thumb in different positions allows the in vivo assessment of its abduction-adduction/flexion excursion. Measurements can also be performed in different positions of the wrist. In our study, the mean excursion amplitudes of the FPL-tendon in seven healthy volunteers were 2.6 (+/- 0.26), 2.6 (+/- 0.25), and 2.7 (+/- 0.63) cm for neutral position, ulnar, and radial deviation of the wrist, respectively. The contribution of the abduction-neutral position route and the neutral position-adduction/flexion route to the total excursion of the thumb varied for the different positions of the wrist, despite the equal excursion amplitudes. The possibility of visualization and the accurate determination of the FPL-tendon excursions is of use in the reconstruction and the transposition of the FPL-tendon. In addition, the shift of the FPL-tendon can be visualized for different positions of the thumb and the wrist. PMID- 8455428 TI - Cognitive functions and brain structures: a quantitative study of CSF volumes on Alzheimer patients and healthy control subjects. AB - In the present study we have investigated the connection between cerebrospinal fluid spaces and cognitive function in patients with senile dementia of Alzheimer type (SDAT) and in successfully aged control subjects. The cerebrospinal fluid (CSF) volumes were measured using a low field MRI technique, and the cognitive functions were assessed with a number of psychometric tests. We found that the SDAT patients showed significantly larger relative volumes in all examined CSF spaces. The largest differences between the groups were found in the volumes of the temporal horns. We also found a significant correlation between the relative CSF volumes in the basal parts of the brain, and episodic memory tests. Significant correlations were also detected between the relative volumes of the lateral ventricles, and degree of dementia as well as between the relative volumes of the lateral ventricles and episodic memory tests. PMID- 8455429 TI - Pulsatile motion artifact reduction in 3D steady-state-free-precession-echo brain imaging. AB - An image can be made from the echo of a steady-state-free-precession and pulse sequences for this purpose have been implemented on various commercial systems under such names as "CE-FAST" and "SSFP" (herein generically termed SSFP-Echo). Such sequences can be employed to achieve strong T2-weighting with reduced T2* effects, but are limited by their sensitivity to flow and motion which produce artifacts. Simple considerations indicate that this sensitivity is primarily related to the (implementation-dependent) moments of the imaging gradients. In this work, MR imaging of the brain using a standard implementation of the sequence with large moment "crusher" gradients on the slice select axis (to dephase the FID of the SSFP) is compared to a modified implementation with reduced moment gradient pulses and different radiofrequency (RF) phase cycling. Asymmetric echo acquisition and narrowed bandwidth was used to further reduce gradient moments. The sensitivity of this sequence to flow and motion artifacts, especially for motion perpendicular to the slice, is thus expected to be significantly reduced. The modified sequence was found to have flow and motion artifacts reduced by a factor of five in the axial plane and a factor of two in the coronal plane. These modifications can thus significantly reduce the flow and motion artifacts commonly seen in conventional images of the SSFP echo with little or no penalty in scan time or signal-to-noise ratio. PMID- 8455430 TI - Correction of intensity nonuniformity in MR images of any orientation. AB - The specialised radiofrequency (RF) coils used in MRI such as head or surface coils can give rise to marked image intensity nonuniformities. There are two situations in which it is essential to correct this: (1) When a global intensity threshold is used to segment particular tissues; and (2) in proton density images, from which the proton concentration can be measured provided that the system gain is uniform or known over the whole image. We describe experiments to determine the magnitude and sources of nonuniformity in a 0.5-T system, and assess methods devised to correct for them in scans of any orientation, including oblique scans at arbitrary angles to the magnet axis and arbitrary offsets from the magnet iso-centre. A correction based on the response of a system to a uniform phantom was implemented. Tests of the correction with orthogonal views demonstrate that the uniformity of images of any orientation can be improved significantly with a correction matrix from just one orientation and still further with two matrices, one axial and the other either coronal or sagittal. We expect further improvements to be possible if gradient coil eddy current effects can be reduced. PMID- 8455431 TI - Sequential analysis of infarcted and normal myocardium in piglets using in vivo gadolinium-enhanced MR images. AB - Gadolinium-enhanced magnetic resonance (MR) imaging was performed before, and 1 and 3 wk after coronary occlusion in domestic piglets. After administration of the contrast agent gadopentetate dimeglumine, two different enhancement patterns within the infarcted region were observed. The first pattern, showing peripheral enhancement of the infarcted region with absence of contrast in the center, was seen at 1 wk after occlusion at 5 min after administration of the contrast agent. The second pattern showed signal enhancement of the center of the infarcted region and was observed at 1 wk after occlusion, 30 min following contrast administration, and at 3 wk after occlusion, both 5 and 30 min following contrast administration. Infarct size and left ventricular (LV) mass by MR imaging, measured 3 wk after infarction, corresponded well with pathologic assessment. LV mass, measured by static and dynamic MR imaging, increased during the period of investigation. It is concluded that gadolinium-enhanced MR imaging clearly identifies infarcted myocardium early and late after coronary occlusion in the piglet. Combined results of infarct size and LV mass can be obtained simultaneously during one imaging procedure. PMID- 8455432 TI - Liver-directed superparamagnetic iron oxide: quantitation of T2 relaxation effects. AB - A new liver-directed superparamagnetic iron oxide nanoparticle preparation, MDL, is described. MDL is derived from previously developed MD particles only by modification of the characteristics of the coating:chemical structure and charge. The biodistribution, pharmacokinetics, and intratissular localization of both 59Fe-labeled MD and MDL particles were analyzed. R2 relaxivities determined in aqueous solution are compared to measurements in liver tissue and to R2 of nanoparticles incorporated into synthetic microcapsules, which represent a simplified cell pattern. T2 relaxation effects of both preparations in liver tissue are discussed relative to physical parameters such as iron oxide core dimension, total particle size, and charge, and pharmacological properties such as biodistribution, pharmacokinetics, and extra/intracellular localization. PMID- 8455433 TI - Histopathological correlations of nuclear magnetic resonance imaging parameters in experimental cerebral ischemia. AB - Changes in the nuclear magnetic resonance (NMR) parameters of spin-lattice relaxation (T1), spin-spin relaxation (T2), proton density (rho), and water diffusion (DNMR) were measured over time together with the histopathological status in three regions of rat brain cortex after permanent middle cerebral artery occlusion (MCA-O). Histological response ranged from severe irreversible damage (necrosis and cavitation) to relatively mild and apparently reversible damage. DNMR was the only NMR parameter which demonstrated a statistically significant change in all three regions of brain studied. Additionally, rho was significantly increased only in the region of brain studied which eventually progressed to necrosis and cavitation. Finally, data are presented which indicate that changes in T2, DNMR, and rho can occur independently of one another. PMID- 8455434 TI - The use of magnetic resonance imaging to track controlled drug release and transport in the brain. AB - A method has been developed to track controlled drug release and transport in the brain. This method entails the use of a polymeric implant to release, over time, a paramagnetically labelled compound into the brain. Magnetic resonance imaging is used to determine the evolving concentration distribution. This method is well suited to other types of intracranial drug delivery systems as well as to track transport in other organs of the body. PMID- 8455435 TI - NMR relaxation enhancement in gels polymerized and cross-linked by ionizing radiation: a new approach to 3D dosimetry by MRI. AB - A new type of tissue-equivalent medium for magnetic resonance imaging of the dose distributions produced by ionizing radiation has been developed. Agarose gel is infused with acrylamide and N,N'-methylene-bis-acrylamide (Bis) comonomers, which are readily polymerized by free radical initiators in de-aerated aqueous solutions. Polymerization and cross-linking induced locally by free radical products of water radiolysis increase the rate of water proton spin relaxation gradually up to doses of about 15 Gy. The slopes of the dose-response curves at 64 MHz are 0.015 and 0.28 s-1 Gy-1 for R1 and R2, respectively. The agarose matrix as well as the high (50% by weight) relative concentration of the cross linker (Bis) per total comonomer limit the spread of polymerization so that the spatial distribution of the radiation dose is faithfully represented in the resultant spatial distribution of relaxation rates. The gel can be imaged with conventional magnetic resonance imaging devices with high spatial resolution and accuracy. In addition, due to the well established effect of the precipitation of insoluble agglomerates of highly cross-linked acrylamide, the optical turbidity of the gel increases gradually with the absorbed dose. This may provide an additional means of visualizing the dose distribution in three dimensions. The major advantage of the acrylamide-Bis-agarose gels over those that depend on ionic chemical dosimeters, for example, Fricke-infused gels, lies in the lack of diffusion of radiation-induced chemical changes subsequent to or concurrent with irradiation. PMID- 8455436 TI - Application of NMR microscopy to the histochemistry study of olives (Olea europaea L.). PMID- 8455437 TI - Carbon-13 magnetic resonance imaging of a human arm. AB - An image of naturally abundant carbon-13 of -CH2- chains of the fatty tissue in a human upper arm is presented. A slotted-tube resonator (STR) for the carbon-13 imaging is described with fabrication details. The carbon-13 image is compared with a proton -CH2- chemical shift image of the same upper arm. PMID- 8455438 TI - Quantitation of in vivo phosphorus metabolites in human brain with magnetic resonance spectroscopic imaging (MRSI). AB - A method for quantitation of in vivo 31P metabolite concentrations in human brain with 31P magnetic resonance spectroscopic imaging (MRSI) is described. The method relies on comparison of brain and calibration phantom measurements, with corrections for coil loading and metabolite magnetic relaxation. Estimated metabolite concentrations for the centrum semiovale in 11 normal adults (mean +/- SD) were: phosphomonoesters = 3.0 +/- 0.7 mM, inorganic phosphate = 0.7 +/- 0.2 mM, phosphodiesters = 10.9 +/- 1.8 mM, phosphocreatine = 2.7 +/- 0.5 mM, and adenosine triphosphate = 2.9 +/- 0.3 mM. These values are similar to previous results obtained from single-volume localized spectroscopy. PMID- 8455439 TI - Magnetic resonance angiography of the neck veins. AB - Time of flight, reduced matrix (64 x 256) MR angiography of the neck veins was performed in four normal subjects and four patients with neck vein thrombosis, either from indwelling catheters (n = 3) or intravenous drug abuse (n = 1). In each case, satisfactory images were acquired. Typical examination times of 3-6 min were required. MR angiography of neck veins gives a unique display of venous anatomy, including collateral veins and occlusions. PMID- 8455440 TI - MR imaging of late onset orbital rhabdomyosarcoma with intracranial extension. AB - Today, patients with alveolar rhabdomyosarcoma have a favorable prognosis with a survival rate of more than 80%, due to modern radiotherapy. However, those patients with secondary meningeal involvement are still afflicted with a mortality rate of 90% unless a different therapeutic approach is taken. We report a case of a young adult with invasion of the tumor into the anterior cranial fossa. MRI aided in the assessment of the intracranial tumor spread and allowed for a direct visualization of the meningeal membranes. The signal characteristics of the tumor and the adjacent tissue in unenhanced and postcontrast MRI is discussed. MRI was clearly superior to CT and indicative for the choice of treatment. PMID- 8455441 TI - The papillary process: a pseudotumor on coronal and sagittal MRI. AB - The papillary process of the caudate lobe can extend posteriorly to lie between the inferior vena cava (IVC) and aorta. Occasionally, the papillary process can wrap around the IVC such that its tip lies posterior to the inferior vena cava. These positions of the papillary process create the potential for its misdiagnosis as a lymph node or mass on coronal and sagittal MRI. To evaluate the frequency that this variant occurs, we retrospectively evaluated contrast axial CT scans in 113 adult patients. Ninety-seven percent had a portion of their papillary process extending posterior to the anterior margin of the IVC. In 66% of the patients, the papillary process overlapped more than 50% of the IVC. In these patients, the papillary process would likely appear as a separate soft tissue structure between the IVC and aorta on coronal MRI. In 12 patients, the papillary process not only extended posterior to lie between the IVC and aorta, but actually extended behind a portion of the inferior vena cava as well. This position of the papillary process could appear as a separate soft tissue structure between the IVC and the diaphragmatic crus on sagittal MRI. The posterior extent of the papillary process between the inferior vena cava and aorta, and occasionally, behind the inferior vena cava, are common anatomical variants, knowledge of which may prevent misdiagnosis on coronal and sagittal MRI. PMID- 8455442 TI - Magnetic resonance image appearance of hamartoma of the breast. AB - The magnetic resonance imaging (MRI) features of a breast hamartoma are presented. The hamartoma was evaluated using several imaging techniques with and without gadolinium-DTPA. This case demonstrates that, in selected cases, MRI is of value as an adjunct to mammography and sonography. PMID- 8455443 TI - Thermal effects of prolonged treadmill exercise in the heat. 1974. AB - Six trained men 21-38 yrs old ran 19-29 km (1.5 to 2.5 hrs) approximately 75% of their VO2 max on a level treadmill in the heat (33.5/21.5 degrees C db/wb, wind velocity 36 m/min). Every 20 min while running they (a) drank 200 ml of 10 degrees C water, (b) drank 200 ml of water at core body temperature, or (c) sponged their faces, arms, and trunks for 2 min with a towel soaked in 10 degrees C water. In another series of experiments each subject (d) hydrated 30 min before the run by drinking 1 liter of water, (e) hydrated and performed (a) above, and (f) hydrated and performed (b) above. Rectal temperature (Tre) and body weight loss (WL) were determined every 30 min and metabolism at 45 min of running. Terminal Tre after (a) through (f) averaged 39.1, 39.3, 39.9, 39.7, 39.1, and 39.3 degrees C respectively. During a control run the corresponding mean Tre was 39.9 degrees C. In a 66.7 kg man with a body weight/surface area (BW/SA) ratio of 37.5 and running at 74% of his VO2 max, Tre rose 0.4 degrees C/1% WL with increasing WL's greater than 2.0% of his initial body weight regardless of the intervention imposed. In another subject weighing 70 kg with a BW/SA ratio of 38.8 and running at 83% of his VO2 max, Tre rose 0.49 degrees C/1% WL over the entire range of WL's.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455444 TI - Functional cervical spinal stenosis: a contraindication to participation in contact sports. PMID- 8455445 TI - Inguinal mass in a college football player: a case study. AB - A 22-yr-old male college football player presented with a 3-wk history of a mass in his right inguinal area. Originally thought by the athlete to be a groin strain, evaluation revealed a large indirect inguinal hernia. Surgical evaluation was obtained to confirm the diagnosis of a 4-cm opening at the external inguinal ring. The hernia completely and spontaneously reduced in the supine position. The athlete was successfully allowed to participate with the use of a truss and underwent an uneventful surgical repair at the end of the season. The diagnosis and treatment of inguinal hernias are reviewed. PMID- 8455446 TI - Restriction of the injury response following an acute muscle strain. AB - Indirect skeletal muscle injuries have been found to occur exclusively near the myotendinous junction (MTJ). Although muscle cells are syncytial and extend far into the muscle belly, the response to this injury has been shown to be limited to a focal area near the MTJ. This study examined single muscle fibers near their site of rupture in order to document structural changes that may help to explain this limited injury response. A partial, nondisruptive strain injury was created in a New Zealand white rabbit extensor digitorum longus muscle. The muscles were left in vivo for 60 min or 6 h before harvesting. The specimens were divided into four groups of single fibers: ruptured fibers (60 min) attached to muscle belly (group I); ruptured fibers (60 min) attached to tendon (group II); ruptured fibers (6 h) attached to muscle belly (group III); and normal, unstretched fibers (60 min) at the MTJ (group IV) (N = 10 for each group). Sarcomeres closest to the site of fiber rupture in the three injured groups (I, II, and III) were hypercontracted, with lengths well below the physiologic range (I: 0.86 +/- 0.08 microns, II: 0.96 +/- 0.09 microns, III: 0.96 +/- 0.21 microns). There was a progressive increase in sarcomere length, which became normal by 300-500 microns away from the site of rupture (I: 2.17 +/- 0.48 microns, II: 2.69 +/- 0.42 microns, III: 2.08 +/- 0.48 microns). The 6-h fibers in group III showed evidence of necrosis before the transition to normal sarcomere spacing occurred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455447 TI - Dietary intakes and biochemical profiles of nutritional status of ultramarathoners. AB - Nutritional status was determined in 17 ultramarathoners registered to participate in the Old Dominion 100-Miler. They had a mean age of 40 +/- 2 yr and ran 67.7 +/- 9.0 miles.wk-1. Subjects maintained 4-d dietary records on two occasions: usual and prerace. Fasting blood samples and 24-h urine collections were also obtained, and concentrations of selected vitamins and minerals were analyzed. Usual and prerace energy, carbohydrate and fat intakes of the ultramarathoners were not significantly different, but usual protein and alcohol intakes were significantly (P < 0.05) higher than prerace intakes. The amount of energy supplied by carbohydrates rose from a usual intake of 54.2 +/- 2.3% to 60.1 +/- 2.4% in the prerace period. Twelve subjects reported taking vitamin/mineral supplements and mean usual and prerace intakes of vitamin and minerals from food and supplements combined met the current recommendations. Biochemical indices of vitamin and mineral status were normal. However, our findings suggest that vitamin B12 metabolism may be altered in ultraendurance runners. Further research is required to determine whether ultraendurance athletes have special nutrition needs. PMID- 8455448 TI - Relationship of oxygen consumption and cardiac output to work of breathing. AB - This study examined the relationship between work of breathing and estimated blood flow to and oxygen consumption by the respiratory muscles. Five subjects performed inspiratory loaded breathing and voluntary hyperpnea while ventilatory work, cardiac output, and oxygen consumption were measured. Blood flow to and oxygen consumption by the respiratory muscles were estimated by subtracting the resting from the working values of cardiac output the oxygen consumption, respectively. Loaded breathing increased cardiac output, but there was no significant correlation with work of breathing, while oxygen consumption was significantly correlated with work of breathing. During hyperpnea both cardiac output and oxygen consumption were correlated with work of breathing. Our results indicate that blood flow and oxygen consumption are increased in a regular pattern with increases in work of breathing. These results may be significant in estimating the demand of the respiratory muscles in disease and exercise. PMID- 8455449 TI - Glycemia and exercise training alter glucose transport and GLUT4 in the Zucker rat. AB - The purpose of this study was to determine the effects of chronic hyperglycemia and/or exercise training on the muscle concentration of the insulin-responsive glucose transporter protein, GLUT4, and on maximally insulin-stimulated hindlimb muscle glucose transport. Five-wk-old lean and obese Zucker rats were randomly assigned to sham-operated control (CTL) or 90% pancreatectomized (PX) groups. Obese-PX animals were further randomized into sedentary or exercise trained groups (15-wk treadmill running for 2 h.d-1, 5 d.wk-1, 15% grade, at 15-18 m.min 1). Muscle GLUT4 protein content and maximally insulin-stimulated glucose transport were determined in gastrocnemius, plantaris, and soleus muscles. At 20 wk, lean-PX displayed mild fasting hyperglycemia but normal insulin levels. Obese PX rats had insulin levels similar to lean-CTL rats but had severe hyperglycemia. Hyperglycemia in lean-PX was associated with a 28% decrease in maximal glucose transport and a 65% decrease in muscle GLUT4 (P < 0.05) compared with lean-CTL. In obese-PX, maximal glucose transport was not affected, but muscle GLUT4 was reduced by 62% (P < 0.05) compared to obese-CTL. Exercise training obese-PX reduced hyperglycemia, increased maximal glucose transport by 45%, and increased muscle GLUT4 by > 2-fold (P < 0.05) compared with obese-CTL. Thus, hyperglycemia associated with PX may be an important factor in the reduction of muscle GLUT4 levels in lean and obese rats. The reduced GLUT4 was accompanied by reduced maximal glucose transport in lean but not obese rats. Exercise training reduced hyperglycemia, normalized glucose transport, and increased muscle GLUT4 in obese PX.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455450 TI - Glycogen resynthesis in skeletal muscle following resistive exercise. AB - The purpose of this investigation was to determine the influence of post-exercise carbohydrate (CHO) intake on the rate of muscle glycogen resynthesis after high intensity weight resistance exercise in subjects not currently weight training. In a cross-over design, eight male subjects performed sets (mean = 8.8) of six single leg knee extensions at 70% of one repetition max until 50% of full knee extension was no longer possible. Total force application was equated between trials using a strain gauge interfaced to a computer. The subjects exercised in the fasted state. Post-exercise feedings were administered at 0 and 1 h consisting of either a 23% CHO solution (1.5 g.kg-1) or an equal volume of water (H2O). Total force production, preexercise muscle glycogen content, and degree of depletion (-40.6 and -44.3 mmol.kg-1 wet weight) were not significantly different between H2O and CHO trials. As anticipated during the initial 2-h recovery, the CHO trial had a significantly greater rate of muscle glycogen resynthesis as compared with the H2O trial. The muscle glycogen content was restored to 91% and 75% of preexercise levels when water and CHO were provided after 6 h, respectively. PMID- 8455451 TI - Effects of surface electrostimulation on the structure and metabolic properties in monkey skeletal muscle. AB - Adaptative changes in skeletal muscle following surface electrical stimulation (SES) were investigated in rhesus monkeys. SES was performed on the triceps brachialis muscle (TB) according to an intermittent pattern. The procedure was carried out for 3 wk, using a current with a medium frequency of 60 Hz normally observed in fast motor axons. The histochemical assays performed on biopsies taken from proximal and distal parts of the TB muscle, before and after the SES program, showed that the distribution of fibers typed by ATPase was unaffected. On the other hand, SES led to an overall increase in the mean fiber cross sectional area (FCSA); P < 0.01 (+13.7%, NS, in proximal portion, vs +31%, P < 0.01 in distal portion). This increase in size occurred in all fiber types. SES was shown to induce an overall increase in capillary to fiber ratio (C/F; +11.06%, NS, in proximal portion, vs +25.93%, P < 0.05 in distal portion). The number of capillaries surrounding fiber Type II (CAFII) was significantly increased by SES (P < 0.05): +3.21%, NS, in proximal portion, versus +21.47%, P < 0.05 in distal portion. Moreover, the number of capillaries surrounding fiber Type I (CAFI) was statistically unaffected by SES. These results suggest that a stimulation of capillary growth may occur following SES-training. Citrate synthase activity was significantly increased after SES. This enhancement in oxidative potential was shown to occur in all fiber types (NADH-diaphorase staining).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455452 TI - Muscle fiber type distribution as estimated by Cybex testing and by muscle biopsy. AB - The purpose of the present study was to derive a regression equation relating variables obtained from a series of noninvasive functional tests in a normal subject population to the fiber type distribution of vastus lateralis muscle (VL) determined using muscle biopsy. All functional tests were designed to distinguish between basic properties of Type II fibers (fast twitch fibers) and Type I fibers (slow twitch fibers) and included assessment of peak torque, power output at nine different angular velocities (60 degrees.s-1 to 300 degrees.s-1), as well as a fatigue test consisting of 60 consecutive contractions at 90 degrees.s-1 to establish fatigue resistance of the knee extensor muscles. Using a stepwise multiple regression procedure, relative torque after 53-55 contractions (T55) in the fatigue test and power output at an angular velocity of 280 degrees.s-1 normalized for fat free mass of the thigh (FFMT) were the best predictors for fiber type distribution, explaining 51.8% of the variance in the proportion of Type II fibers in VL. No other measured variable met entering criteria. Subgroup analyses revealed a higher peak torque/FFMT, higher power/FFMT values at angular velocities of 200 degrees.s-1 and higher, and lower relative torque beyond 30 contractions in the fatigue test for the fast twitch group, FTG (subjects with > 60% Type II fibers, N = 8) as compared with the STG (subjects with < 45% Type II fibers, N = 9). Results from the present study suggest that two simple functional tests on a Cybex dynamometer yield reasonable estimates of the fiber type distribution in VL. PMID- 8455453 TI - Gradual and rapid weight loss: effects on nutrition and performance in male athletes. AB - We studied seven male wrestlers and three judo athletes (weight 55-93 kg) during two weight reductions. In the "gradual" procedure (GP), a 5.0 +/- 0.4% (mean +/- SEM) weight loss was achieved in 3 weeks by energy restriction. In the "rapid" procedure (RP), 6.0 +/- 0.6% of body weight was lost in 2.4 days by fluid and diet restriction and forced sweating, and followed by a 5-h "loading" (food and drinks ad libitum). The net weight loss after GP and loading was 2.7 +/- 0.5%. Protein intakes (4-d food records) during GP and RP were 71 +/- 16 and RP 56 +/- 17 g.d-1, respectively. Carbohydrate intakes were 239 +/- 56 (GP) and 182 +/- 55 g.d-1 (RP). During GP and RP, mean thiamin, magnesium, and zinc intakes were at or below the respective recommendation. Thiamin, riboflavin, potassium, iron, and zinc status, assessed from blood chemistry, remained stable during both procedures. Changes in vitamin B6 indicator (E-ASTAC) and S-magnesium concentration were different (P < 0.01) between the procedures, suggesting negative trends during GP. Sprint (30-m run) and anaerobic (1-min Wingate test) performance was similar throughout the study. Following GP, vertical jump height with extra load increased by 6-8% (P < 0.01). Jumping results were not affected by RP. Hence, < or = 5% loss in body weight by either method did not impair experienced athletes' performance. PMID- 8455454 TI - Effect of stepping rate on energy costs during StairMaster exercise. AB - The responses to a self-selected stepping pattern (random) on a StairMaster 4000PT were compared with those obtained in response to the rates established by the manufacturer (cadence) in men (N = 14) and women (N = 14). During the random test the subjects stepped at their own natural, self-selected rate and distance. In cadence trial the subjects were required to step in time with a metronome at a predetermined rates of 60, 77, 95, and 112 steps.min-1. Each trial consisted of four, 5-min continuous workloads during which HRs were recorded and expired air was analyzed using an automated open-circuit gas system each minute. All size dependent variables (i.e., VE and lO2.min-1) as well as relative VO2 (mlO2.kg 1.min-1) were significantly (P < 0.01) higher for the men across all stages and between methods. Although the random test produced slightly higher oxygen consumption values than the cadence trial, these differences were not significant (P > 0.05). The actual METs were significantly (P < 0.01) higher at all stages except at the lowest stepping rate for both methods compared with those estimated by the manufacturer. Equations were established to estimate actual MET costs: Men's METs = 2.675 + 0.935 (rate); women's METs = 2.934 + 0.817 (rate). Cross validations of 0.975 and 0.957 were obtained on an additional group of men (N = 8) and women (N = 11), respectively. PMID- 8455455 TI - Effect of pacing strategy on cycle time trial performance. AB - Despite interest in competitive strategy by coaches and athletes, there are no systematically collected data regarding the effect of differences in pacing strategy on the outcome of middle distance (2-4 min duration) events. In this study different pacing strategies were evaluated using a 2-km time trial on a bicycle attached to a wind load simulator. Well-trained subjects (N = 9) performed five separate time trials with the pace during the first 50% of the trial experimentally constrained within the usual real world range from very slow (approximately 55% of best time) to very fast (approximately 48% of best time). Serial VO2 was measured to estimate the oxidative contributions to the trial and accumulated O2 deficit and postexercise blood lactate measured to estimate the anaerobic contribution to the trial. The evenly paced trial (first 1 km = 50.9% final time) produced the fastest total time. The starting pace to final time relationship was described by a U shaped second order polynomial curve with the nadir for final time at a starting pace of 51% of best total time. There were no systematic differences in serial VO2, accumulated O2 deficit, or postexercise lactate that could account for the pacing related variations in performance. The data support the concept of relatively even pacing in middle distance events with negative consequences for even small variations in this strategy. PMID- 8455456 TI - Reliability and variability of indicators of heart-rate monitoring in children. AB - We describe the daily heart-rate patterns and the between-day and within-day reliabilities of several heart rate indicators measured in 131 Anglo-, African-, and Mexican-American children aged 5-7 yr. Heart rates were measured over 12 waking hours with a Quantum XL Telemetry heart rate monitor. The percent of heart rates 25% above resting heart rate, an index of physical activity heart rate (PAHR-25 index), was found to have the highest within-day (0.92) and between-day (0.81) reliabilities. The Spearman-Brown prophecy formula indicated that only 9.3 h of observation would be needed to maintain a within-day reliability of 0.90. The percentage of heart rates 50% above resting heart rate (PAHR-50) was found to have slightly lower within-day (0.88) and between-day (0.56) reliability. Principal components analysis revealed that the PAHR-25 and PAHR-50 indicies only had one component throughout the day. The PAHR-25 and PAHR-50 indicies were weakly correlated with age, suggesting that they may be good indicators of relative PAHR. Male children had higher (P < or = 0.025) PAHR-25 index scores than females. There were no gender or ethnic differences in the PAHR-50 index. PMID- 8455457 TI - Oxygen consumption using the K2 telemetry system and a metabolic cart. AB - The purpose of this study was to compare measurements of oxygen consumption (VO2), ventilation (VE), and respiratory rate (RR) between a relatively new portable, telemetry system (K2) and a system that has been shown to be valid and reliable. Duplicate measurements were made at rest and during four levels of exercise in 10 subjects. Heart rate values were comparable for exercise at the same work level during gas collection using the two systems, indicating that the metabolic stresses were similar. Oxygen consumption measurements were significantly lower using the K2 system compared with a metabolic measurement cart (MMC). There was no significant difference in VE, but RR was lower for measurements made with the MMC. Compared with the MMC, the K2 system uses a slightly different formula to calculate VO2 because the content of carbon dioxide in expired air is not measured. To determine differences resulting from the method of calculating VO2, MMC measurements were applied to the formula used by the K2 system, and K2 values were adjusted using the RER values obtained from the MMC. There were no differences between these calculated values and the values obtained directly from either the MMC or the K2 system. Consequently, we concluded that the lower VO2 values obtained with the K2 system were attributed to the method of collecting and analyzing expired air, rather than to the method of calculating VO2. PMID- 8455458 TI - VO2max estimation from a submaximal 1-mile track jog for fit college-age individuals. AB - The primary purpose of this study was to develop a submaximal field test for the estimation of maximal oxygen uptake (VO2max) using a 1-mile track jog. A second purpose was to determine the accuracy of the 1.5-mile run in estimating VO2max for both male and female subjects. VO2max was measured in 149 relatively fit college students (males = 88, females = 61) 18-29 yr using a treadmill protocol (mean +/- SD; VO2max = 47.7 +/- 6.3 ml.kg-1 x min-1). Multiple regression analysis (N = 54) to estimate VO2max from the submaximal, steady-state 1-mile track jog yielded the following validation (V) model (r(adi) = 0.87, SEE = 3.0 ml.kg-1 x min-1): VO2max = 100.5 + 8.344* GENDER (0 = female; 1 = male) - 0.1636* BODY MASS (kg) - 1.438* JOG TIME (min.mile-1) - 0.1928* HEART RATE (bpm). To help ensure that a submaximal level of exertion was realized for the 1-mile track jog, elapsed jog time was restricted to > or = 8.0 min for males and > or = 9.0 min for females and exercise HR to < or = 180 bpm. Cross-validation (CV) of the 1 mile track jog comparing observed and estimated VO2max (N = 52) resulted in radj = 0.84, SEE = 3.1 ml.kg-1 x min-1. Multiple regression analysis (N = 50) to estimate VO2max from the 1.5-mile run (V:N = 49, radj = 0.90, SEE = 2.8 ml.kg-1 x min-1; CV: N = 47, radj = 0.82, SEE = 3.9 ml.kg-1 x min-1), used elapsed run time, body mass, and gender as independent variables.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455459 TI - Cumulative subject index. Volumes 168-174, 176-194. PMID- 8455460 TI - Alternative mode of replication of human immunodeficiency virus: a hypothesis. AB - For diagnosis of Human Immunodeficiency Virus (HIV) infection by the recently developed Polymerase Chain Reaction (PCR), the two commonly used clinical samples are either the peripheral blood monocytes (PBMC) or the plasma of the infected individuals. In the former instance, DNA is extracted from PBMC. The integrated proviral DNA is then amplified using HIV specific oligonucleotide primers. In the latter instance, RNA is extracted from plasma. This is reverse transcribed in vitro into cDNA by using extraneous reverse transcriptase. This cDNA is then used as a target in PCR experiments with HIV specific primers. In contrast we have recently used DNA directly extracted from plasma of infected individuals. This DNA was used for amplification of HIV genome with primer pairs specific for HIV. An interesting outcome of this study was a model to explain the presence of DNA of HIV in the plasma. We suggest that possibly there is an alternative mode of replication of HIV. Apart from the obligatory integration of the DNA of HIV into the DNA of lymphocytes as provirus, several additional copies of the DNA are also made which remain unintegrated. These probably exist as a housekeeping repertoire of the viral genome. These DNA molecules may be released into the circulation along with the newly formed mature virion particles during the usual course of replication and release of the virus. In our experiments with direct extraction of DNA from plasma, these unintegrated DNA of HIV may act as the target for PCR to give positive signals with HIV specific primers. PMID- 8455461 TI - Oncogenes, antioncogenes, and a hypothesis on cancer therapy, i.e. the origin of cancer, and the prevention of its activity. AB - Existing data indicates there is a set of genes--oncogenes--whose increased or abnormal expression causes cancer. Another set of genes--antioncogenes--control oncogene expression. Implied is that cancer is neither infectious nor contagious, i.e. one cannot catch cancer, and cancers are fundamentally similar. Fetal cells can be used instead of immunosuppressing drugs, regulate antigen-antibody action reaction, and may be in some instances genetically wholesome. They, therefore may be useful to compensate for the immunological breakdown or deficiency which results in active cancer. PMID- 8455462 TI - Oncogerminative hypothesis of tumor formation. AB - The oncogerminative hypothesis of tumor formation states that during malignant transformation of somatic cells part of the germinative cell genome is activated. This part determines the phenotype property of the germinative cell: its potential immortality realized during its life cycle. In malignant cells this activated part of the genome also determines immortality in its life cycle. The life cycle of the cell may be divided into five stages: 1) the reproduction stage under the influence of promotors; 2) the stage of multicellular oncospheroid formation (the parody of blastocyst) characterized by heterogeneous composition of cellular population consisting of three major phenotypically different cells: oncogerminative ones (stem), oncotrophoblast (fulfilling trophic function) and oncosomatic ones (differentiated) imitating germinative, trophoblast and somatic cells of the embryo respectively; 3) the stage of malignant tumor formation which consist of the vascularization of the oncospheroid and its growth under the conditions of anatomic contacts with the organism; 4) the stage of disaggregation of the oncogerminative cells which manifested in the organism by process of metastatic spreading; 5) the stage of formation of metastatic tumors. The change of the ratio of oncogerminative, oncotrophoblast and oncosomatic cells in metastatic tumors is a basis of tumor progression. PMID- 8455463 TI - Abnormal fibroblast clone--an alternative hypothesis for pathogenesis of rheumatic heart disease. AB - Fibrosis is an ubiquitous process. Any tissue injury can culminate in fibroblast accumulation and multiplication with collagen synthesis and deposition. A large number of chronic disease states such as rheumatic heart disease, constrictive pericarditis, cirrhosis of the liver, renal interstitial fibrosis, chronic interstitial lung disease are characterized by extensive fibrosis. In many of these patients, when there is no clinical or laboratory evidence of previous injury, it is presumed that the initiating insult/injury had been 'subclinical'. I propose that 1) the fibroblasts can be activated even in the absence of preceding inflammation, 2) it is the type of 'fibroblast clone' in a given individual together with the 'milieu' in a particular tissue/organ which decides the occurrence and severity of subsequent fibrosis. This fibroblast clonal theory adds a new dimension to the pathogenesis of various disease states and may help in identifying those at high-risk and in evolving a unified therapeutic strategy for amelioration of various disorders characterized by extensive fibrosis. PMID- 8455464 TI - Cardiac autonomic control mechanisms in Chagas' heart disease. Therapeutic implications. AB - According to the neurogenic theory of Chagas' heart disease, the cardiac parasympathetic abnormalities of chagasic cardiac patients are due to a selective destruction of the cardiac parasympathetic neurons. Trypanosoma cruzi would selectively destroy the cardiac vagal neurons, during the acute stage of the disease. However, these cardiac parasympathetic abnormalities are found mainly in chagasic patients who are in very advanced stages of the disease. Furthermore, the extent of cardiac parasympathetic involvement correlates with the degree of left ventricular dilation. Cardiac parasympathetic abnormalities, and a reciprocal sympathetic hyperactivity are also present in non-chagasic cardiac patients. Modern medical treatment, with sympatholytic drugs, prevents ventricular dilatation and prolongs life in these non-chagasic cardiac patients. Consequently, if chagasic cardiac patients have ventricular dilatation-related parasympathetic abnormalities; it is of the utmost importance to ask: first, do they also have a progressive activation of their neurohumoral systems?; and second, would they benefit from sympatholytic drugs?. PMID- 8455466 TI - Foot ulceration: hypotheses concerning shear and vertical forces acting on adjacent regions of skin. AB - During gait the plantar surface of the foot experiences distributed shear and compressive stresses due to tangential and vertical forces respectively. At any given point under a foot, the ratio of tangential/vertical forces gives a value (mu Rmin) for the minimum coefficient of friction required to prevent slipping. If mu Rmin is greater than the actual coefficient of friction (mu A), then localized slipping will occur. Three possible scenarios exist which could lead to skin ulceration: at a localized area the skin may tend to slip (i) towards, (ii) away from or (iii) parallel to a neighboring skin region where mu Rmin < or = mu A (i.e. a region that doesn't slip). The first of these possibilities is similar in concept to the loading conditions that lead to a carpet becoming 'wrinkled', i.e. one region of the carpet slips towards another that is stationary. The second and third possibilities would tend to cause tearing in the carpet or shearing of its fabric respectively. In terms of skin breakdown the relative importance of each of these biomechanical hypotheses needs to be determined. PMID- 8455465 TI - Possible etiology for euthyroid sick syndrome. AB - Euthyroid sick syndrome is possibly due to an increase in Triac (a T3 analogue) and/or Tetrac (a T4 analogue). Triac and/or Tetrac possibly feed back on the pituitary/hypothalamus region and cause a secondary hypothyroidism. This is possibly analogous to such diverse conditions as fetal thyroid function and black bear hibernation. PMID- 8455467 TI - Multiple sclerosis and prions. AB - The etiology of Multiple Sclerosis (MS) is unknown. Existing epidemiologic data suggests that MS can be an infectious disease. MS used to be classified as one of the 'slow infections'--many of these are caused by prions. Prions are small, proteinaceous, infectious particles--distinguished from viruses by the absence of intrinsic nucleic acids. In a contrast to the 'classic' prional diseases (Kuru, Scrapie or Creutzfeldt-Jacob Disease) that in CNS affect primarily neurons, the 'target' cell in MS is an oligodendrocyte. This may explain differences in disease presentation. This paper presents a pathophysiological model of MS based on the assumption that MS is a prional disease. Processes leading to the demyelination in Multiple Sclerosis seem also to involve lymphocytes, astrocytes and macrophages as well as the interferon system. PMID- 8455468 TI - Chronic fatigue syndrome: influence of histamine, hormones and electrolytes. AB - The chronic fatigue syndrome is poorly understood. We believe the underlying causes in many atopics and women are a persistent infection and hypersensitivity to the immune-suppressive effects of histamine and certain pathogens. We believe much to the symptomatology can be explained by all four types of hypersensitivity (Gell and Coombs classification) in reaction to a pathogen, electrolyte disturbances which include sometimes permanent changes in cell membranes' ability to pass electrolytes, sometimes permanent biochemical changes in mitochondrial function, and disturbances of insulin and T3-thyroid hormone functions. We also explain in detail what 'fatigue' means for these patients. We present evidence from the medical literature for the plausibility of our hypotheses. PMID- 8455469 TI - The iodine-selenium connection: its possible roles in intelligence, cretinism, sudden infant death syndrome, breast cancer and multiple sclerosis. AB - Several diseases and disorders display spatial patterns that suggest the involvement of both selenium and iodine deficiencies, or excesses, in their etiologies. It is suggested that many of these similarities in geographical distribution occur because both elements influence thyroid hormone metabolism. PMID- 8455471 TI - Barrier dynamics in physiological aging. AB - Approximately 40 years ago the author initiated work which led to the 'Diffusion Theory of Aging'. Due to the net differential rate of deposition of interstitial constituents the transfer of molecules through this milieu becomes modified with advancing age so that delivery of nutrients to the interior of the cells becomes inappropriate to maintain the physiology of youthful cells. Later it was proposed that superhomeostatic events could leave irreversible residues which would further contribute to this 'malnutrition'. The role of pericellular proteins and the plasma membrane was then unknown. Now they are much better understood as final barriers to the entrance and departure of molecules into and from the cell interior and they can be modified by age. Thus is proposed the 'Barrier Dynamics Hypothesis of Aging'. PMID- 8455470 TI - Analgesics abuse: theoretical and practical considerations. AB - Three important issues must be addressed in any attempt to determine whether combination painkillers play a role in analgesic nephropathy. The first issue, namely that of a causal link between the combination itself and nephrotoxicity, has never been adequately documented. On the contrary, there is much evidence that the combination as such has no influence whatsoever. The cause of the nephrotoxicity is most likely the painkilling mechanism, i.e. the antagonism to prostaglandins; the most potent prostaglandin-antagonists, the non-steroidal anti inflammatory drugs, whether used in combination or singly, also most frequently cause renal pathology. The second issue, i.e. the safety of combination painkilling drugs in comparison with that of single substances, is intimately bound up with the advantages of the former with respect to both activity and the activity-side-effects ratio. The third issue, abuse, should be recast in a broader context. The central element here is not the painkilling drug but rather the labile personality of the user in conjunction with a more or less stressful environment in which a wide variety of drugs and stimulants are available and taken for better 'coping'. To a great extent analgesics abuse can be prevented by information (i.e. social medicine). In a broader perspective, man experiences considerable difficulty adapting to the sweeping social, technological and ideological changes of recent decades, and this transition contributes in no small measure to the analgesics problem. It should be a priority of government to find remedies for this state of affairs. PMID- 8455472 TI - Life prolongation with dietary restriction: protection of genome and core metabolism and the role of glycosylation. AB - Life prolongation with dietary restriction can be found in much of the animal kingdom and thus is a phenomenon that is evolutionarily conserved. We propose that one benefit of this is protection of the genome at lower dietary intake, perhaps by reduction of glycosylation related alterations and retardation of age related impairment of DNA repair. Dietary restriction is inferred to maintain a major portion of metabolism in central pathways, since additional intake can be manifest by changes in metabolism, weight gain, and (presumably) a higher incidence of diseases which may interfere with reproductive ability. PMID- 8455473 TI - Immune discrimination of self and nonself: a unified theory for the induction of self tolerance among thymocytes and mature peripheral T cells. AB - A comprehensive model of immunological self tolerance is described which is based on the unique tenet that interactions between T cell antigen receptors (TcR) and specific MHC ligands may vary in efficacy (the ability of an MHC ligand to catalyze TcR-mediated activation). Based on this postulate, two interrelated mechanisms are described to explain how self tolerance is induced among immature thymocytes and mature peripheral T cells, respectively. In the thymus, APC apparently present a diverse array of self MHC ligands (complexes of self peptides and MHC glycoproteins) to clonotypic T cells. According to the first mechanism, immature thymocytes that efficaciously bind specific MHC ligands undergo TcR-mediated activation and programmed cell death whereas those that nonefficaciously bind MHC ligands are not activated and thereby escape negative selection. The latter T cells undergo positive selection and eventually constitute the mature T cell repertoire. This model of thymic selection ensures that interactions of mature T cells with self in peripheral tissues are predominantly nonefficacious. According to the second mechanism, clonotypically diverse T cells and individual APC comprise an integrative unit that measures antigenic complexity of the local environment as a basis to enable or disable immunogenic responses by mature T cells. T cells recognize efficacious MHC ligands (E) via the TcR/CD3 complex but are also able to detect nonefficacious MHC ligands (N) by conserved signal transduction pathways that are initiated upon cell-cell contact with APC. Clonotypic T cells relay E or N signals by conserved feedback pathways back to APC. APC integrate and compare large numbers of E or N signals to derive an E/N ratio.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455474 TI - Science in search of psychiatry. AB - The evidence of the major physical sciences' developments, based on their primary reductionist analyses, including nuclear power, analysis of the gene DNA, the creation of new chemical structures etc, is around us and self evident in our daily social life. This reductionist model can be seen in the doctor treating the disease as such and/or its specific pathology or pathogenesis. Medical practice does involve a social interaction between individuals. The social dimension presents for research the interface between the individual's mind and the views of his/her society or social group. This interface becomes critical in a psychiatric consultation as the locus of the disease, if any, is not clear and may not even be at the interview. These social dimensions are examined in terms of the Queen of the Sciences, Mathematics. PMID- 8455475 TI - Cerebral cortex function: a general principle. AB - The columns in the cerebral cortex have two separate levels of activity and only a few of the columns are at a high level of activity simultaneously. Arguments for this functional organization are given. PMID- 8455476 TI - Wittgenstein's schizophrenia in moonlight. PMID- 8455477 TI - The efficacy of surgical treatment of cancer. AB - This paper is the result of a study to provide a scientific basis for the claim that surgery is effective in extending the life of cancer patients. The study failed to locate any scientifically valid evidence for the claim. The paper includes an outline of some of the factors which led to surgery becoming an 'accepted' treatment for cancer and a discussion of how the problem of ethics continues to prevent proper trials being carried out to prove the efficacy of surgery. Alternative ways of obtaining evidence for the efficacy of surgery are discussed including the Graphical Method, Comparative Studies, Survival Rates, Comparison of Incidence and Mortality, Epidemiological studies and Comparison of Survival after treatments based on two different hypotheses about what cancer is. Each analysis showed no reliable evidence of surgery's efficacy or, where evidence for efficacy could be inferred from the evidence, an alternative conclusion was also possible. Poor methodology, invalid assumptions and definitions, and poor logic are some of the characteristics of this field of medicine. This paper brings together results from scientific papers published over the past 35 years which, taken together, suggest that the reason for the lack of evidence for surgery's efficacy might be that it is not effective because cancer is a systemic rather than a localised disease when first diagnosed. PMID- 8455478 TI - The thesis of the alkaline milieu in oncology: a review. AB - An alkaline milieu is a common factor in some carcinomas of the oropharynx and oesophagus, the stomach, the bronchus, the cervix and the large bowel. The hypothesis is advanced that a change to an alkaline pH enhances the mitotic activity of mucous cells and that this change can be often avoided by alterations in diet and habit. PMID- 8455479 TI - Ascorbic acid and cholesterol gallstones. AB - Decreased activity of cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme in the catabolism of cholesterol to bile acids, is known to result in increased biliary cholesterol concentration and supersaturation of bile. Supersaturation of bile by cholesterol is a necessary condition for cholesterol gallstone formation. In guinea pigs, the hepatic concentration of ascorbic acid affects the catabolism of cholesterol: hypovitaminosis C reduces cholesterol 7 alpha-hydroxylase activity. Cholesterol gallstones are frequently found in ascorbic acid-deficient guinea pigs. Risk factors for cholesterol gallstones in humans include obesity, aging, estrogen treatment, pregnancy and diabetes. Plasma ascorbic acid levels are reduced in these groups. Vegetarian diets, which typically have high ascorbic acid contents, protect against gallstones. Since ascorbic acid effects the rate limiting step in the catabolism of cholesterol in the guinea pig and many human risk groups for cholesterol gallstones are associated with reduced ascorbic acid levels, ascorbic acid may play a contributory role in human gallbladder disease. PMID- 8455480 TI - The role of reactive oxygen species, antioxidants and phytopharmaceuticals in human immunodeficiency virus activity. AB - Currently, several prominent researchers are investigating the role of reactive oxygen and free radicals in the activation of latent HIV in infected individuals. Early clinical applications of free radical scavengers and plant-based antioxidant systems have shown promise of efficacy in altering this process. This manuscript demonstrates a premise for the existence of 'oxidative stress' as an important element in HIV progression and a basis for the use of these phytopharmaceutical substances. PMID- 8455482 TI - Inducing viral immunity without a vaccine--possible use with human immunodeficiency virus. AB - Induction of allergic contact dermatitis over warts (verrucae vulgaris) causes viral immunity and resolution of the warts in a large percentage of cases. Human immunodeficiency virus could be removed, concentrated, and placed back into the patient's own skin at a site of contact dermatitis. PMID- 8455481 TI - A novel antiviral strategy for HIV infection. AB - The replication of human immunodeficiency virus (HIV) may be modulated in part by host factors such as DNA methylation. Hypermethylation of the HIV provirus may suppress viral replication and play a role in the establishment of latency. HIV seropositive individuals have decreased levels of metabolites involved in methylation. It is proposed that metabolites such as S-adenosylmethionine (SAM), methylcobalamin and methyltetrahydrofolate be explored as potential therapeutic agents in HIV infected individuals. PMID- 8455483 TI - The cause of AIDS. AB - There is growing evidence that allogeneic cells, rather than viruses or bacteria are the cause of AIDS. It is proposed here that these allogeneic cells are sperm cells which induce the production of anti-sperm antibodies. Anal sex, genital ulcers and female circumcision allow sperm cells to be absorbed into the body and thus produce AIDS. Also these three factors plus the use of sperm contaminated blood transfusions can explain the high incidence of AIDS among African black women. It is concluded that the practice of anal sex (men and women recipients) is widespread in Africa and that knowledge of such practice is suppressed because of society pressures. PMID- 8455484 TI - Investigating serious and series crime. PMID- 8455485 TI - Police officer, lawyer or doctor involved in the investigation and prosecution of cases of child abuse. PMID- 8455486 TI - A case of measles--can children refuse treatment? Ethical and legal issues relating to the right of children to consent to or refuse treatment. PMID- 8455487 TI - H.M. inspectorate of prisons. PMID- 8455488 TI - Uniform oscillating gradient produced by spherical birdcage resonator. AB - The theory and operation of a resonator which produces a uniform oscillating magnetic field gradient is described. When the resonator is operated at audio frequency, it will produce the oscillating magnetic field gradient required for use in spatial encoding in rapid acquisition magnetic resonance imaging. PMID- 8455489 TI - MRI-guided noninvasive ultrasound surgery. AB - In this study, the feasibility of using magnetic resonance imaging (MRI) to detect tissue necrosis induced by focussed ultrasound beams was investigated. It was shown that lesions produced in dog's thigh muscle in vivo were clearly visible in T2-weighted images and that the lesion dimensions measured from the images correlated with the postmortem measurements of the visible tissue damage. It was also shown that the sonications can be done in the magnet and that the lesions are visible immediately after the sonications with increasing image contrast as a function of time. These results showed that MRI can be used to direct and monitor on-line noninvasive ultrasound surgery. This may have a major impact in future patient treatments. PMID- 8455490 TI - Ultrasound contrast-detail analysis: a preliminary study in human observer performance. AB - Results of a human observer performance study using a new ultrasound contrast detail (CD) phantom are reported. The new phantom allows estimates of the fundamental statistical uncertainties involved in CD analysis. Results of these experiments show that observers generally considered to be "trained" require experience at the specific task of low-contrast target detection under signal known exactly (SKE) conditions, and that observers require an orientation period at the beginning of each observation session to obtain stable responses. The results obtained in this study can be used to estimate the number of independent images, observers, and repeat observation sessions required for a desired uncertainty in CD curves, and show that 10% fractional standard deviations are obtainable with modest observer effort. PMID- 8455491 TI - Acoustic power calibrations of cylindrical intracavitary ultrasound hyperthermia applicators. AB - Preliminary clinical results indicate that some tumors can be heated well utilizing cylindrical ultrasound sources placed in body cavities. In this paper a simple method for measuring the acoustic power from cylindrical intracavitary transducers will be described. The radially propagating acoustic field was converted to a beam with a single propagation direction by a brass reflector, and the radiation force generated by this beam on an absorbing target was measured. The power output of several clinical intracavitary arrays varied significantly between identically shaped transducer elements. The results show that it is important to measure the acoustic power output from each element prior to its clinical use. The radiation force technique is simple and sensitive and can be easily adapted to be used as a routine clinical quality assurance method. PMID- 8455492 TI - Photon beam characteristics on the MM50 racetrack microtron and a new approach for beam quality determination. AB - The photon beams of the MM50 racetrack microtron have special characteristics which make them more suitable than conventional photon beams for precision radiation therapy with good dosimetric control. The beam flattening is obtained by the scanning of an elementary beam instead of using a flattening filter. This will give a number of advantages such as the possibility to optimize field flattening to individual field forms and field sizes. The radiation quality is the same across the whole beam, which gives smaller changes in dose profiles with depth and also makes it easier to perform careful dose planning. Beam collimation is mainly performed by a multileaf collimator and the special design of the treatment head gives nearly ideal characteristics for dose determination in an arbitrary point in the treatment fields. The output factor has been shown to depend almost solely on scattering within the treatment field. The conventional methods for beam quality characterization have been found less suitable at high energies and a new method based on HVL measurements in water is proposed. PMID- 8455493 TI - Experimental and theoretical x-ray imaging performance comparison of iodine and lanthanide contrast agents. AB - Contrast agents based on the lanthanide elements gadolinium and holmium have recently been developed for magnetic resonance imaging (MRI). Because of the increased atomic number of these elements relative to iodine, these new compounds, used as x-ray contrast agents, may yield higher radiographic contrast, and hence improved x-ray image quality, relative to conventional iodinated compounds, for clinically useful x-ray spectra. This possibility has been investigated, in independent experimental and theoretical studies, for two x-ray imaging systems: a digital radiographic system, using an x-ray image intensifier (XRII) and charge-coupled device (CCD) detector; and a conventional screen/film system, using a Lanex Regular screen. Iodine, gadolinium, and holmium contrast agents were investigated over a wide range of concentration-thickness products (0.1-0.6 M cm) and diagnostic x-ray spectra (60-120 kVp). A simple theoretical model of x-ray detector response predicts the experimental radiographic contrast measurements with a mean absolute error of 8.0% for the XRII/CCD system and 5.9% for the screen/film system, and shows that the radiographic contrast for these two systems is representative of all XRII and screen/film systems. An index of image quality is defined, and its dependence on radiographic contrast, x-ray fluence per unit dose, and detective quantum efficiency (DQE) is shown. Theoretical values of the index, predicted by our model, are then used to compare the performance of the three contrast agents for the two systems investigated. In general, iodine performance decreases steadily with increasing kVp, gadolinium performance has a broad maximum near 85 kVp, and gadolinium outperforms holmium. Gadolinium outperforms iodine for spectra above (and vice versa below) about 72 kVp, depending slightly on spectrum filtration, object thickness, and detector type. Thus, raising the kVp to shorten exposure times or reduce x-ray tube heat loading results in a loss of image quality with iodine, but not with gadolinium. Similarly, beam-hardening artifacts in performing video densitometry with iodine would be reduced with gadolinium. Gadolinium-based contrast agents are thus shown to offer several practical advantages over conventional iodinated contrast agents. PMID- 8455494 TI - Sampling techniques for the evaluation of treatment plans. AB - Sampling techniques using randomly distributed points and regular Cartesian grids were compared for the evaluation of volume, dose-volume histogram, tumor control, and normal tissue complication probabilities in radiation treatments. Particularly, the uncertainties associated with each sampling technique in estimating the dose-volume histograms for several dose distributions are analyzed in detail. It is found that the estimation of these parameters using sampling points on a regular Cartesian grid is, in general, significantly more efficient than using random points. This finding is different from other published results. The choice of grid size for sampling was analyzed according to the AAPM recommended uncertainty on the dose delivered to the patient. It was concluded that when grid sampling is used, a grid size of 0.5 cm is adequate for most plans to meet the guidelines. PMID- 8455495 TI - Cylindrical dose distributions in pseudodynamic rotation radiosurgery: an experimental study. AB - A linac-based radiosurgical technique is reported which produces cylindrical isodose distributions covering cylindrical targets of arbitrary orientations within the patient's head. The technique uses rectangular collimators and 4 degrees of freedom: gantry and couch rotation, as defined by a previously known dynamic rotation technique, collimator rotation, and collimator length adjustment. The relationship between the four parameters is derived and because of its complexity, the cylindrical dynamic rotation technique is introduced as a pseudodynamic technique. For cylindrical targets, the cylindrical pseudodynamic technique is comparison to the standard spherical technique produces considerable dose savings to healthy tissue surrounding the target and gives a similar or better dose fall-off outside the target. PMID- 8455496 TI - Shaping of photon beams from electron linear accelerators in radiation therapy. AB - The method of calculation of the bremmstrahlung yield and angular distributions based on the semianalytical model described by Kovalev [Vtoricnoe izlucenie uskoritelej elektronov (Atomizdat, Moscow, 1979)] was analyzed. The specially written computer program was used to optimize the geometry of the collimators and the flattening filter design for radiation therapy purposes. The x-ray beam shaping system thus designed was installed in the 4-MeV linear Limex accelerator working at the Cancer Center in Warsaw (Poland). By comparing the calculated beam distributions with the experimental data, the agreement between theory and measurements was found to be within about +/- 3%. PMID- 8455497 TI - Correction for distortion in a beam outline transfer device in radiotherapy CT based simulation. AB - In using a CT scanner as a radiation therapy simulator, it would be helpful to be able to transfer the beam outline from the computer plan to the patient's skin. A beam outline transfer device has been constructed and installed on a Siemens' DRH CT scanner gantry. The planned treatment beam geometry from a 3-D computerized simulation and planning system can be projected onto the patient's skin surface accurately and efficiently. The positioning accuracy achieved is within +/- 0.1 cm over a 20 cm x 20 cm field. Integrating the device into the CT scanner, simplifies the device and reduces the cost over an externally mounted device. Two unsuccessful methods to correct the projection distortions are also mentioned. In order to achieve the reported beam outline transfer accuracy, a system based on our empirically derived calibration procedure is described. PMID- 8455498 TI - A simple method of producing depth ionization data for electron energy constancy check. AB - A simple method has been developed to reproduce depth ionization data of electron beams for energy determination. The method utilizes a simple set of equipment, a combination of a specially designed wedge-shaped polystyrene phantom and a linear array of detectors, to collect the necessary data. The wedge-shaped phantom provides varying depths to various detectors in the array. The ionization readings received from the detectors were corrected for off-axis ratio and plotted against corresponding ray-line depths to produce depth ionization curves. The instrument setup was fast and simple. The relevant data, for a high-energy linear accelerator with multiple electron energies, were collected in minutes. The depths of 80% and 50% ionization determined by this method were found to differ by 2 and 3 mm, respectively, at the most, with those determined by a conventional method. PMID- 8455499 TI - Assessment of a linear accelerator for segmented conformal radiation therapy. AB - Segmented conformal radiation therapy is a new computer-controlled treatment technique under investigation in which the target volume is subdivided into thick transverse segments each of which is then treated individually by rectangular transverse abutting fields. In order to obtain uniform dose at abutments, the machine isocenter remains fixed in the patient and field edges are defined by independently moving focused collimator jaws to give matching geometric divergence. Mechanical variation in jaw and gantry positioning will create some dose variation at field abutments. Film dosimetry was used to study the radiation field positioning accuracy and precision of a commercial linear accelerator. A method of field position calibration was developed using multiple nonabutting fields exposed on the same radiograph. Verification of collimator jaw calibration measurements was performed using multiple abutting fields exposed on a single radiograph. Measurements taken over 5 months of clinical accelerator operation studied the effects of simple jaw motion, simple gantry motion, and combined jaw/gantry motion on jaw position precision and accuracy. The inherent precision and accuracy of radiation field positioning was found to be better than +/- 0.3 mm for both jaws with all types of motions except for the Y2 jaw under combined jaw/gantry motion. When the ability to deliver abutting beams was verified in clinical mode, the average dose variation at abutments was less than 6% at all gantry angles except for one. However, due to accelerator software limitations in clinical mode, the settings for collimator positions could not take advantage of the maximum accuracy of which the hardware is capable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455500 TI - Contrast enhancement of portal images by selective histogram equalization. AB - Because of the high energy of the treatment beam, contrast of portal verification films is very poor. A simple contrast enhancement technique is described which we have labeled selective histogram equalization (SHE), to improve visualization of double-exposure portal images and this facilitate the beam verification process. The technique performs separate histogram equalization on the treatment- and open field sections of double-exposure portal images. Delineation of the treatment field edge and separation into two regions is performed automatically for off line portal radiographs by a strategic combination of Sobel filtration and morphological processes. Analyses of images processed by SHE and other adaptive histogram equalization techniques indicate that SHE produces improved contrast enhancement with minimal addition of noise or artifacts, thus simplifying the beam verification procedure. The simple implementation of an automatic SHE process with on-line portal systems is also discussed. PMID- 8455501 TI - Head-scatter factors in rectangular photon fields. AB - Head-scatter factors were measured for a range of field sizes of rectangular shape from a linear accelerator that provides 6 and 25 MV photon beams. For a given field length and width, exchange of the inner and outer collimator pairs produces differences in the head-scatter factor of up to about 2% and 3% in open and wedged fields, respectively. Dependence on elongation deviates by up to 2% from that given by the equivalent squares. Such effects can easily be taken into account by using head-scatter data that have been directly measured in rectangular fields or by applying empirical corrections to values for square or equivalent square fields. PMID- 8455502 TI - An improvement in the use of plaster bandage for patient contouring. AB - The setting time of plaster bandage used for patient contouring can be decreased by adding potassium sulfate to the dip water. A small amount of this inexpensive chemical can have a significant effect. This improvement gives the physicist sufficient control of the process so that contours may be made from plaster as quickly as they are made with stiff wire, but with improved accuracy. PMID- 8455503 TI - Comparison of calculated and measured heterogeneity correction factors for 125I, 137Cs, and 192Ir brachytherapy sources near localized heterogeneities. AB - The influence of tissue and applicator heterogeneities on brachytherapy dose distributions is not well understood, despite widespread use of shielded applicators in intracavitary therapy. Heterogeneity correction factors (HCF) have been measured using a silicon diode detector arising from bounded heterogeneities consisting of lead, steel, titanium, silver, aluminum, and air cylinders near brachytherapy sources of 125I, 137Cs, and 192Ir. In addition, transverse-axis dose distributions for the three sources in homogeneous water were measured for distances of 0.2 to 16.0 cm. For each point of measurement, relative diode readings were simulated by a Monte Carlo photon transport code utilizing accurate models of the source internal structure, the experimental measure geometry and the source-strength calibration geometry. Comparison of measured and calculated HCF's reveals excellent agreement (1%-3% average) over a wide range of materials, diameters, and thicknesses. In addition, Monte Carlo simulation not only accurately reproduced the relative transverse-axis dose distributions in homogeneous medium, but was able to predict the variation of diode response with photon energy with an accuracy of 3% over the range of 30-662 keV. Our measurements demonstrate that HCF's vary by as much as 60%-100% with distance and heterogeneity diameter for a fixed thickness. Finally, silicon diode measurements of HCF (denied as reading with heterogeneity/reading in homogeneous medium) is shown to lead to errors of 5%-30% for 137Cs and 192Ir sources in the presence of high-atomic number shielding materials. This paper concludes, that Monte Carlo simulation is a powerful, convenient and accurate tool for investigating the long neglected area of brachytherapy heterogeneity corrections. PMID- 8455504 TI - Experimental determination of 32P dose backscatter factors at and near soft tissue boundaries. AB - Beta-ray dose backscatter factors with respect to soft tissue were measured using an extrapolation chamber. The beta-ray dose backscatter factor is a measure of the change effected in absorbed dose to a soft-tissue medium when part of the medium is replaced by a material other than soft tissue (i.e., a scatterer); the source is located at the boundary between the two media. The dependencies of backscatter factor on scatterer atomic number and on source geometry are investigated, and the variation of backscatter factor with distance from the boundary is determined. For a 32P point source, backscatter factors with respect to Mylar, a soft-tissue substitute, at 0.55 mg/cm2 from the boundary, are, 29.65[0.12]%, 31.07[0.24]%, 19.30[0.48]%, 16.27[0.35]%, 5.46[0.11]% and 26.44[0.02]% for bismuth, tungsten, cadmium, copper, aluminum, and air scatterers, respectively. Backscatter factors measured for a 32P planar source are generally smaller than those for a point source. The variation of backscatter factor with distance from the boundary is well represented analytically by sums of exponentials. Therefore, the rate of decrease of backscatter factor with distance can be specified by a relaxation length, defined as the depth through which the backscatter factor is reduced by 1/e, where e is the base of the natural logarithm. For example, with a 32P planar source, relaxation lengths in Mylar are 588[7] mg/cm2 and 238[2]mg/cm2 for bismuth and aluminum scatterers, respectively. Qualitative interpretation of backscatter factor depth profiles is presented. In addition, the variations of backscatter factor with scatterer atomic number and with source geometry are discussed with reference to existing experimental findings on beta particle reflection. PMID- 8455505 TI - One-dimensional scatter-subtraction method for brachytherapy dose calculation near bounded heterogeneities. AB - Neglect of tissue and applicator heterogeneities in brachytherapy treatment planning is due in part to lack of accurate, general, and fast three-dimensional (3D) dose-computation algorithms. A novel dose-calculation algorithm that accounts for the lateral dimensions and location of the heterogeneity as well as its thickness has been developed. For simple 2D, water-equivalent density heterogeneities, the algorithm is shown to be applicable to a wide range of photon energies and is 500-1000 times more efficient than Monte Carlo photon transport calculations. The model is based upon reducing the bounded 2D heterogeneity problem to two 1D problems by dividing the scattering volume into two regions: A cone-shaped region that subtends the heterogeneity with its apex at the source and the complementary cone that contributes scatter dose by diffusion around the heterogeneity. The input data consist of precalculated scatter-to-primary ratios (SPRs) for collimated isotropic point sources. The central-axis "mini-beam" problem for a slab heterogeneity is solved by a simple 1D scatter integration model that accounts for both the thickness of the heterogeneity and its location relative to the point of interest. The scatter contribution arising outside the mini-beam is modeled as the difference in SPRs corrected for transmission through the heterogeneity. The algorithm agrees, on average, with sample Monte Carlo calculations within 1% to 7% for 125I, 192Ir, and 100 keV point sources along the axes of water-equivalent cylindrical heterogeneities (rho = 0-12.6 g/cm3, 3.6, and 24 mm diameters, and dose perturbation factors of 0.44-1.33 relative to the homogeneous case). The potential of generalizing the scatter-subtraction approach to encompass 3D heterogeneities, those consisting of high-atomic number media, and those of irregular shape, is discussed. PMID- 8455506 TI - Routine verification of strength of 137Cs brachytherapy sources using a NaI detector. AB - An inexpensive and easy method of calibration of brachytherapy 137Cs tubes is described. Cesium brachytherapy sources are calibrated relative to an NIST calibrated source. The detection system is a NaI detector and single channel analyzer with the window set on the photo peak. PMID- 8455507 TI - A safe method of analysis for mechanical damage in spherical radioactive sources used in remote afterloading brachytherapy devices. AB - The examination of brachytherapy sources in a quality assurance program can result in significant exposure to staff. Even though exposure may be within prescribed limits attempts should be made to reduce such exposure to as low as reasonably achievable (ALARA concept). In this report, a system that can be used to examine small spherical radiation sources while minimizing exposure to staff is described. PMID- 8455508 TI - Quality assurance for variable-length catheters with an afterloading brachytherapy device. PMID- 8455509 TI - A preliminary phantom study on a proposed model for quantification of renal planar scintigraphy. AB - A method for estimation of the absolute renal activity within background activity in renal planar scintigraphy will be presented. This method corrects for oversubtraction of background activity with consideration of background activity of the kidney volume, and employs the depth-independent buildup factor (DIBF) method for the correction of attenuation and scatter of photons. This method requires the depth and thickness of the organ and the thickness of background for a background activity correction. The transmission factor (TF) for a volume source is derived from integrating TF for a thin source over the thickness of the organ for the DIBF method. To validate this method, phantom studies with various uniform background activity concentrations were performed and the data were compared with conventional background subtraction that do not consider the organ's volume. The results showed that with the conventional background subtraction method at all depth activity was underestimated with errors of 5%-30% for organ/background concentration ratios of 5-40, while this method estimated the true count rate with errors of less than 5%. More accurate quantifications of renal functions such as renal uptake, glomerular filtration rate (GFR) and renogram may be obtained by this proposed method on the planar images. PMID- 8455510 TI - Evaluation of inherent gray-level dynamic range in a digital image using the runs test and join-count statistics. AB - The dynamic range of the gray level of a digital image is limited by the noise it contains. Two statistical methods called "runs test" and "join-count statistic" are used to measure the noise level in a digital image. A residual image is formed by subtracting an original image from its smoothed version. Theoretically, the noise level in the residual image should be identical to that in the original image. The noise level is determined by examining each bit plane of the residual image individually starting from the least significant bit up to the bit plane whose statistic does not show a random pattern. Images from three digital modalities: computerized tomography, magnetic resonance, and computed radiography are used to evaluate the gray-level dynamic range. Both methods are easy to implement and fast to perform. PMID- 8455511 TI - A method for selective removal of out-of-plane structures in digital tomosynthesis. AB - The quality of the reconstructed images in Digital Tomosynthesis is often limited by the presence of artifacts due to blur from planes other than the fulcrum plane. A technique has been developed for the separation and subsequent removal of unrelated structures from the reconstructed plane. The method involves the reconstruction of the blur originating in user-selected "noisy" planes as it appears on the plane of interest. This is achieved by projecting the reconstructed images of the selected plane on the image formation plane for all viewing angles, and subsequently, synthesizing its blurred image on the plane of interest. There are no restrictions as to the identity of the planes to be removed. Reproduction of the noise is performed using the tomosynthesis algorithm itself, thus the technique can be modified to suit any reconstruction algorithm. The proposed technique was implemented on the Multiple Projection Algorithm and was experimentally evaluated using a radiotherapy simulator unit. PMID- 8455512 TI - The general solution to the Bloch equation with constant rf and relaxation terms: application to saturation and slice selection. AB - The general solution to the Bloch equation in the rotating frame which includes the effects of relaxation during a constant amplitude, off-resonance rf field has been developed. The solution is used to monitor the transient approach to steady state saturation levels during off-resonance irradiation applied continuously or in pulses to systems with arbitrary relaxation rates. The time course of the magnetization during amplitude modulated rf pulses is followed with the general solution and the transverse relaxation time dependence of typical slice profiles is examined. The calculations serve to illustrate the generality of the solution. A thorough discussion of various computational concerns is provided. PMID- 8455513 TI - Development of a high quality film duplication system using a laser digitizer: comparison with computed radiography. AB - A high quality film-duplication system was developed in order to improve the image quality of duplicated radiographs and to recover improperly exposed films. The system consists of a laser film digitizer, a laser film printer, a workstation, and a magneto-optical disk. Radiographs are digitized by the laser digitizer, processed by the computer for image enhancement, and then printed on a film by the laser printer. A nonlinear density-correction technique is employed in recovering improperly exposed radiographs using the H&D curve of the screen film system. Using the new duplication system in our department, the average recovery rate was over 80% for chest and abdominal films rejected due to over- or underexposed. The basic imaging properties of the duplication system were compared with those of a Computed Radiography (CR) system and a conventional screen-film system. For low spatial frequencies, the MTF of the CR system is superior to that of the digital duplication system; however, for high spatial frequencies, the MTF of the duplication system is superior. The noise in the duplication system is about half of that in the CR system. PMID- 8455514 TI - A technique of scatter-glare correction using a digital filtration. AB - A scatter-glare correction technique for x-ray images acquired with an antiscatter grid was developed. In the technique, the scatter-glare image was estimated from exposure conditions and subtracted from the acquired image. The basic procedure in the estimation of the scatter-glare image is convolution filtering; however, the novel aspects of the technique are as follows: (1) To estimate the scatter-glare intensity, a formula that does not include the term of object thickness was used. With this formula, the correction can be performed, even for nonuniform phantoms; (2) To estimate the scatter-glare distribution, the experimental scatter-glare point spread function (PSF) was directly used as a convolution kernel. Although the shape of the PSF changed slightly for water thicknesses of 5-25 cm, we applied the PSF measured at a water thickness of 15 cm to the correction experiments. For the stepped water phantom (10-20 cm), scatter glare estimation produced an average error of 10%, with respect to the lead bar data. Furthermore, the improvement of image quality and quantitative accuracy resulting from the correction was examined. PMID- 8455515 TI - Automatic segmentation of liver structure in CT images. AB - The segmentation and three-dimensional representation of the liver from a computed tomography (CT) scan is an important step in many medical applications, such as in the surgical planning for a living-donor liver transplant and in the automatic detection and documentation of pathological states. A method is being developed to automatically extract liver structure from abdominal CT scans using a priori information about liver morphology and digital image-processing techniques. Segmentation is performed sequentially image-by-image (slice-by slice), starting with a reference image in which the liver occupies almost the entire right half of the abdomen cross section. Image processing techniques include gray-level thresholding, Gaussian smoothing, and eight-point connectivity tracking. For each case, the shape, size, and pixel density distribution of the liver are recorded for each CT image and used in the processing of other CT images. Extracted boundaries of the liver are smoothed using mathematical morphology techniques and B-splines. Computer-determined boundaries were compared with those drawn by a radiologist. The boundary descriptions from the two methods were in agreement, and the calculated areas were within 10%. PMID- 8455516 TI - Y2O2S:Eu phosphor screens evaluation. AB - The x-ray luminescence of Y2O2S:Eu phosphor screens is studied both in transmission and in reflection mode observation. Detailed experimental data concerning the dependence of the absolute efficiency on the tube voltage and the screen's thickness are presented and comparisons to another rare earth phosphor material (Y2O2S:Tb) are given. With the help of theoretical calculations based on the Hamaker-Ludwig model all the experimental data are explained and the intrinsic efficiency and scattering coefficients of the phosphor are estimated. PMID- 8455517 TI - Absolute volumetric blood flow measurements using dual-energy digital subtraction angiography. AB - In recent years, as a solution to the well-documented problems associated with visual interpretation of coronary arteriograms, more physiologic means of assessing coronary artery stenosis are being investigated. Absolute arterial blood flow assessed as a function of time can be a valuable aid in the analysis of functional significance of arterial lesions and obstructions. An absolute volumetric blood flow measurement technique using a motion immune dual-energy subtraction technique is being investigated, where the kVp and filtration are switched at 30 Hz. The low- and high-energy images are corrected for scatter and veiling glare before subtraction. In this technique, the absolute arterial blood flow is calculated by combining the videodensitometric analysis of spatial and temporal aspects concerning the contrast propagation through the arterial bed using tissue suppressed energy subtracted images. The blood flow measurement technique was validated using a pulsatile pump and a flow chamber imaged over a Humanoid chest phantom. A 20-MHz Doppler flow probe was used to validate the measurement of phasic volumetric blood flow. The measured (M) and known (K) mean blood flow for the entrance vessel technique and the videodensitometric calibration technique were related by M = 1.14K - 0.12 ml/s (r2 = 0.98) and M = 1.12K - 0.23 ml/s (r2 = 0.90), respectively. The results indicate that phasic volumetric blood flow can be measured using a CCD camera in conjunction with real time dual-energy subtraction. PMID- 8455518 TI - Mammography focal spot measurement with a star pattern: techniques to avoid inaccuracies. AB - The increased emphasis on mammography acceptance testing and quality control make the star pattern test an essential component of the procedure for diagnosing poor resolution due to large focal spots. In this paper procedures for calculating magnification and the correct angle of the star pattern to use are described. The preferred placement of the star pattern in the field and proper exposure technique is also discussed. PMID- 8455519 TI - Display equalization: a new display method for portal images. AB - A method of displaying portal images which permits the user to optimize the display contrast (windowing and leveling) without clipping parts of the image has been developed. The method finds the average signal (brightness) in small regions of the image, generally 1/64th of the total image area. The difference between the average signal in each small region and the global average over the entire image is subtracted from the original image. This eliminates changes in average signal that occur over large spatial dimensions, such as those due to varying patient thickness, without obscuring changes in signal that occur over small spatial dimensions, such as those due to anatomic structures. The technique is conceptually simple, does not introduce any visually distracting noise into the image, and is not computationally intensive. The display method has been shown to work well with images acquired from a TV camera-based imaging system used in radiation therapy. PMID- 8455520 TI - The anatomy lesson: software puts the body on screen. PMID- 8455522 TI - Physicians under surveillance. The National Practitioner Data Bank. PMID- 8455521 TI - Containing costs in Minnesota's health care system. A summary of the Minnesota Health Care Commission report to the Legislature. PMID- 8455523 TI - Dentists charging patients for AIDS-protection costs. PMID- 8455524 TI - Helmet law would put us on the road to good health. PMID- 8455525 TI - Park Nicollet responds to change with some of its own. PMID- 8455526 TI - Malnutrition definition revised. PMID- 8455527 TI - Nutrition support in bone marrow transplant recipients. AB - Bone marrow transplantation is a complex therapy designed as curative for a variety of malignant and nonmalignant diseases. It is a highly invasive procedure that uses high-dose chemotherapy and may also include radiation treatment. This results in immunosuppression that is often followed by infection, graft-vs-host disease, pulmonary complications, veno-occlusive disease of the liver, and metabolic and nutritional abnormalities. Parenteral nutrition has been the mainstay of nutrition support in patients undergoing bone marrow transplantation. Parenteral nutrition has not been uniformly successful in improving nutritional status or outcome. Enteral nutrition offers many theoretical advantages but is often not well tolerated. Coordinated efforts of the health care team are needed to optimize the nutrition support of these complicated cases. PMID- 8455528 TI - Managing nutrition problems in transplant patients. AB - Patients who undergo organ transplantation receive immunosuppressive drugs in the posttrans-plant period. All of these drugs influence host metabolic response or alter nutrient intake. One of the most prominent aspects of the posttransplant period is the occurrence of hyperlipidemia, which may require dietary or pharmacologic control. Dietary recommendations for this patient population include limiting carbohydrate intake, restricting caloric intake to maintain ideal body weight, and maintaining a low cholesterol/saturated fat diet. PMID- 8455529 TI - Nutrition and transplantation. PMID- 8455530 TI - Treatment of hyperemesis gravidarum with nasogastric feeding. AB - Hyperemesis gravidarum, an antepartem disorder characterized by severe nausea and vomiting, is usually a benign condition with a favorable outcome. Although no increase in fetal or maternal morbidity results, the disorder has deleterious effects on both nutrition and everyday life. The authors describe a treatment protocol for hyperemesis gravidarum that uses continuous infusion of an iso osmolar tube-feeding product and their experiences with its use in 30 patients. Uniformly good symptom relief was obtained by this technique, thus avoiding the need for more invasive therapy. It is proposed that this treatment is a safe and effective means of managing severe nausea and vomiting during early pregnancy. PMID- 8455531 TI - Nutrition management of the hepatic transplant patient. AB - Patients who are candidates for liver transplantation are predisposed to severe nutritional depletion because of their underlying hepatic dysfunction. Nutrition associated complications, particularly infection and poor wound healing, are common causes of morbidity and mortality among adults with chronic liver disease and malignancy who are referred for liver transplantation. During the preoperative period, maintenance or repletive nutrition is provided to the patient with hepatic failure. The patient's postoperative period is characterized by the catabolic response to a major operation, the progressive improvement of hepatic graft function, and the persistent compensatory renal abnormalities that are associated with liver failure. The nutrition management of the patient with liver failure has been well described. Nutrition intervention during the intraoperative and postoperative periods remains enigmatic. The following case report describes the nutrition management of a liver transplant recipient in the intraoperative and postoperative periods. PMID- 8455532 TI - Home nutrition support patient education materials. AB - The practice of providing specialized enteral and parenteral nutrition to patients in the home setting has expanded nationwide during the past decade. Accompanying this growth has been an increased need for education of patients, families, and care providers in techniques of administering intravenous and tube feedings safely after discharge from the hospital. To meet this demand for information, written home nutrition support (HNS) education materials have been developed by hospital nutrition support teams, patient education specialists, home care providers, and formula manufacturers. The time and financial costs of developing these materials may be prohibitive in certain institutions that need HNS education resources. A directory of the printed materials available has been compiled to facilitate communication and exchange of HNS education information among institutions. The directory is presented with this article, with important characteristics to consider in the development of HNS education materials. PMID- 8455533 TI - The current role of small-bowel transplantation in intestinal failure. AB - Short bowel syndrome is the clinical manifestation of a fundamental reduction in the functional intestinal absorptive surface area and malabsorption. The development of total parenteral nutrition has improved the natural course of this disease. Home parenteral nutrition-related complications continue to generate significant morbidity and mortality for these patients. Small-bowel transplantation is an alternative to home parenteral nutrition. There are significant risks of graft rejection and the potential complications of long-term immunosuppression. Small-bowel transplantation is an option, but it should be reserved for patients no longer considered candidates for continued home parenteral nutrition. PMID- 8455534 TI - Teaching and researching in higher education--how is it possible? PMID- 8455535 TI - Relationship of a preceptorship experience to the views about nursing as a profession of baccalaureate nursing students. AB - In nursing education, preceptorship experiences have gained much popularity as a teaching/socializing strategy. This strategy is assumed to assist students in bridging the practice-theory gap and in becoming socialized to the professional role of the nurse but there has been minimal research on the effectiveness of the strategy in the professional socialisation of nursing students. This study examined the effects of a preceptorship experience on baccalaureate nursing students' perceptions about professional nursing before and after 4-week and 7 week preceptorship experiences. Variables such as the length of the experience and the educational preparation of preceptors were included to determine their influence on students' perceptions of the professional role. A pre-test/post-test design was used. Senior baccalaureate nursing students with a preceptorship component in their program formed the non-randomised convenience sample (n = 103). Data collection was through the administration of the Valiga Concept of Nursing Scale (1982). Results showed that, while there were no significant differences in students' perceptions after a 4-week preceptorship experience, a significant difference was found after the 7-week preceptorship experience. Interestingly, no significant differences were discerned when the two groups were compared post preceptorship. The students paired with baccalaureate prepared nurses had a significantly greater increase in score than the students paired with diploma prepared nurses. PMID- 8455536 TI - Illiteracy: implications for nursing education. AB - Possession of an internally consistent body of knowledge from which principles and practice can be derived is the pre-eminent characteristic of professional groups. Active, enquiring minds are required as nursing struggles to develop such a base. Yet, recent evidence, such as the 1992 report of the Economic Council of Canada, suggests a pervasive decline in basic language competencies. The illiteracy of candidates entering professional schools of nursing is creating problems for students, faculty and the profession, with ramifications for public safety and professional growth. This article describes problems and proposes action that can, and must, be taken to remedy the situation. PMID- 8455537 TI - Professional socialisation of nursing students as an outcome of a senior clinical preceptorship experience. AB - The study purpose was to examine the effects of a senior clinical preceptorship experience on the professional socialisation of nursing students. Corwin's (1961) conception of the professional nursing role and literature on professional socialisation provided the model for the study. A three-group, pre- and post-test design was used. The voluntary, non-randomised sample was drawn from 242 senior community college, baccalaureate and RN-BScN nursing students. Instruments were the Lawler-Corwin (1988) Nursing Role Conception Scale and the Lawler-Stone (1988) Health Care Professional Attitude Inventory. Demographic data were collected. One-way ANOVA was used to compare the mean scores among the three groups. For statistically significant (p < 0.05) F tests, Student-Newman-Keuls multiple comparison tests were used to determine which pairs of groups were different. Pre-post scores were compared using paired t-tests. Following the preceptorship, on the Lawler-Stone subscales, the groups became more professional and more similar in attitude. On Corwin's three role conceptions, the total group reported less role conflict, with the community college students having the least and the RN-BScN students the most amount of conflict. The mixed results emphasise that professional socialization requires further research, especially as an outcome of a preceptorship experience for RN-BScN students. PMID- 8455538 TI - Selecting potential nurses: a review of the methods. AB - The following paper presents an overview of the literature in relation to personnel selection and its particular application to the selection of candidates for nurse education. In industry and indeed general management circles within the National Health Service, dynamic methods are being used to select middle and higher management personnel. Yet the largest group of National Health Service employees to be selected, nurses, whose training costs represent no small amount in annual budgets, appear to be accepted on highly inconsistent and subjective grounds. Material derived from personnel management and occupational psychology demonstrates the importance of systematic staff selection and the resulting discussion questions why nursing retains such methods for selecting student nurses. PMID- 8455539 TI - The future of the specialist nurse teacher: two different models explored. AB - The demand for more specialised nurse educators is increasing, yet the nature and direction of this specialisation remains unclear. In this paper the strengths and limitations of two different models are evaluated focusing on the organisation and management of education, integration of theory with practice, the skill of teaching itself and the implications for clinical practice. PMID- 8455540 TI - The role of nurse teachers in the empowerment of nurses through research. AB - This paper explores some of the difficulties faced by nurse teachers supporting students in research studies. The issues raised in this paper were identified through a small scale exploratory study of the teachers role. Areas discussed include teachers' preparation for the research component of their role and their interpretation of research-based activity. Practical issues such as the time required to undertake research studies and methods of teaching research are also explored. It is argued that nurse teachers are a key group in increasing research knowledge within the nursing profession, yet attention to this important part of the role is lacking. If nurses are to be empowered through research it is suggested that nurse teachers are a key group in bridging a gap between the rhetoric and reality of research-based practices in nursing. PMID- 8455541 TI - Quality assurance in nurse education. AB - Nurse education in common with all areas of health is undergoing rapid and wide ranging change. The selection and implementation of quality assurance strategies is now very much a current issue in colleges of nursing up and down the United Kingdom. In this article the author examines one model of quality assurance and looks at possible strategies for success. PMID- 8455542 TI - Using experiential learning methods with larger groups of students. AB - Experiential learning methods have been advocated for teaching interpersonal skills in nursing courses. Tutors and lecturers are often teaching larger groups of students on Project 2000 courses and this may lead to difficulties in using experiential learning methods. This paper offers two types of structure for using such methods based on the notion of student-facilitation. The paper also highlights the need for experiential learning groups to be evaluated effectively and the learning that takes place in them to be linked to the clinical nursing arena. PMID- 8455543 TI - The use of video cameras in one college of nursing. AB - The use of video cameras in nurse education is reviewed and a small scale investigation into the usage of video cameras in one medium-sized college of nursing and midwifery is described. It was found that only 3% of staff had used a video camera more than six times a year. On these occasions the camera was used primarily to record student role play. Analysis and discussion of the respondents' use and suggested use of the video camera is included. PMID- 8455544 TI - Education can never be neutral--teaching for subversion. AB - Nurse education is in the turbulent throws of political, demographic and ideological change, as many colleges adopt a curriculum to produce a new breed of nurse, through 'Project 2000'. Essentially however, those preparing these students for professional practice are often entrenched in the traditional and hierarchial tutor-student relationships with which we are all familiar. This paper seeks to explore the work of some radical educationalists with a view to presenting subversive teaching as a credible, and potentially desirable, entity. To cope with change and survive as a profession, nurse education cannot afford to throw out the bedpan along with its contents. PMID- 8455545 TI - Problem-based learning packages: considerations for neophyte package writers. AB - Adopting problem-based learning (PBL) as the major educational approach in the implementation of a nursing curriculum requires the development of numerous learning stimulus packages. When reviewing the experience of the Division of Nursing within the Faculty of Health at the University of Western Sydney, Macarthur in Australia, several considerations for package writers were identified and are discussed. These include needs assessment, integration of the curricula content strands, multi-media learning stimuli, context, role and the incorporation of ongoing client management. The need for nurturance of writers and peer review of the developed packages is also addressed, as is a review of the impact of different learning stimuli. PMID- 8455546 TI - [93rd annual meeting of the Japan Surgical Society. Sendai, April 21-23, 1993. Abstracts]. PMID- 8455547 TI - Bending of DNA segments with Saccharomyces cerevisiae autonomously replicating sequence activity, isolated from basidiomycete mitochondrial linear plasmids. AB - Previous studies have indicated that DNA bending is a general structural feature of sequences (ARSs) from cellular DNAs of yeasts and nuclear and mitochondrial genomic DNAs of other eukaryotes that are capable of autonomous replication in Saccharomyces cerevisiae. Here we showed that bending activity is also tightly associated with S. cerevisiae ARS function of segments cloned from mitochondrial linear DNA plasmids of the basidiomycetes Pleurotus ostreatus and Lentinus edodes. Two plasmids, designated pLPO2-like (9.4 kb), and pLPO3 (6.6 kb) were isolated from a strain of P. ostreatus. A 1029 bp fragment with high-level ARS activity was cloned from pLPO3 and it contained one ARS consensus sequence (A/T)TTTAT(A/G)TTT(A/T) indispensable for activity and seven dispersed ARS consensus-like (10/11 match) sequences. A discrete bent DNA region was found to lie around 500 bp upstream from the ARS consensus sequence (T-rich strand). Removal of the bent DNA region impaired ARS function. DNA bending was also implicated in the ARS function associated with a 1430 bp fragment containing three consecutive ARS consensus sequences which had been cloned from the L. edodes plasmid pLLE1 (11.0 kb): the three consecutive ARSs responsible for high level ARS function occurred in, and immediately adjacent to, a bent DNA region. A clear difference exists between the two plasmid-derived ARS fragments with respect to the distance between the bent DNA region and the ARS consensus sequence(s). PMID- 8455548 TI - Molecular analysis of the gene encoding a rice starch branching enzyme. AB - The sequence of a rice gene encoding a starch branching enzyme (sbe1) shows extreme divergence from that of the rice gene, that is homologous to bacterial glycogen branching enzyme (sbe2). sbe1 is expressed abundantly and specifically in developing seeds and maximally in the middle stages of seed development. This expression pattern completely coincides with that of the waxy gene, which encodes a granule-bound starch synthase. Three G-box motifs and consensus promoter sequences are present in the 5' flanking region of sbe1. It encodes a putative transit peptide, which is required for transport into the amyloplast. A 2.2 kb intron (intron 2) precedes the border between the regions encoding the transit peptide and the mature protein, and contains a high G/C content with several repeated sequences in its 5' half. Although only a single copy of sbe1 is present in the rice genome, Southern analysis using intron 2 as a probe indicates the presence of several homologous sequences in the rice genome, suggesting that this large intron and also the transit peptide coding region may be acquired from another portion of the genome by duplication and insertion of the sequence into the gene. PMID- 8455549 TI - Function of the Escherichia coli nucleoid protein, H-NS: molecular analysis of a subset of proteins whose expression is enhanced in a hns deletion mutant. AB - The expression of numerous Escherichia coli cellular proteins was previously demonstrated to be greatly enhanced in a hns deletion background, relative to the levels in wild-type cells. In this study, a subset of such proteins, expression of which is affected by H-NS, was partially purified, and the genes coding for some of the proteins were identified and characterized. Two of the proteins thus characterized, 19K and 17K, were found to be encoded by previously predicted genes that are located adjacent to, and downstream of, the trpABCDE operon (27.6 min on the E. coli genetic map). The genes coding for the other two proteins, 10K L and 10K-S, are located at 77.5 min on the genetic map. Their nucleotide sequences were determined and revealed that they may constitute an operon. To characterize the putative promoters for these genes, a set of promoter-lacZ transcriptional fusion genes was constructed on the E. coli chromosome. The results of such promoter-probe analyses indicated that H-NS represses the expression of these genes at the transcriptional level. Furthermore, H-NS appeared to exhibit relatively strong affinity for the putative promoter sequences in vitro. These results are compatible with the hypothesis that H-NS functions as a transcriptional repressor. PMID- 8455550 TI - The genome of the tropical tree Theobroma cacao L. AB - 2C values for angiosperms vary over 2500-fold and a positive correlation exists between C-value and latitude in herbaceous plants. Woody plants differ from herbaceous plants in chromosome size and C-value. In addition, tropical hardwoods have smaller chromosomes than other tropical plants and do not share the correlation of minimum generation time with genome size seen in herbaceous plants. Theobroma cacao is a tropical hardwood cultivated for its beans, which are used to make chocolate and cocoa butter. Its cytology is typical of the pantropical and subtropical family Sterculiaceae. Its small chromosomes, single secondary constriction, and lack of C-banding suggest a small genome. The genome size of T. cacao, measured by reassociation kinetics, is 2.01 x 10(8), which is small compared to both temperate and tropical plants previously studied. We also provide data on the melting point, base composition, and relative extent of methylation (at sites most commonly methylated in higher plants), of T. cacao DNA. PMID- 8455551 TI - DNA specificity of Escherichia coli deoP1 operator-DeoR repressor recognition. AB - We have studied the importance of the specific DNA sequence of the deo operator site for DeoR repressor binding by introducing symmetrical, single basepair substitutions at all positions in the deo operator and tested the ability of these variants to titrate DeoR in vivo. Our results show that a 16 bp palindromic sequence constitutes the deo operator. Positions outside this palindrome (positions +/- 9, +/- 10) can be changed without any major effect on DeoR binding. Most of the central 6-8 bp of the palindrome (positions +/- 1, +/- 2, +/ 3) can be substituted with other nucleotides with no or only minor effects on DeoR binding, while changes at position +/- 4 and +/- 5 give a more heterogeneous response. Finally, changes at positions +/- 6, +/- 7 and +/- 8 severely disrupt DeoR binding. PMID- 8455552 TI - Structure, evolution and expression of the mitochondrial ADP/ATP translocator gene from Chlamydomonas reinhardtii. AB - The first AUG in the Chlamydomonas reinhardtii ADP/ATP translocator (CRANT) mRNA initiates an open reading frame (ORF) which is very similar (51-79% amino acid identity) to other ANT proteins. In contrast to higher plants, no evidence for a long amino-terminal extension was obtained. The 5' non-transcribed region of the single-copy CRANT gene contains sequence motifs present in other C. reinhardtii nuclear genes. Four introns, whose positions are not conserved in other ANT genes, interrupt the protein coding region. A short heat shock specifically reduces CRANT mRNA levels. CRANT mRNA levels were unaffected by a mutation in photosynthesis. In a dark/light regime CRANT mRNA levels are high in the dark phase and low in the early light phase. Data on translation initiation sites, splice junctions and the codon preferences of C. reinhardtii nuclear genes were compiled. With the exception of two rare codons, ACA and GGA, the CRANT gene exhibits the biased codon usage of C. reinhardtii nuclear genes that are highly expressed during normal vegetative growth. PMID- 8455554 TI - Analysis of naturally occurring late flowering in Arabidopsis thaliana. AB - We have examined the late-flowering behavior of two ecotypes of Arabidopsis thaliana, Sf-2 and Le-0. The late-flowering trait segregates as a single dominant gene in crosses with the early-flowering Columbia ecotype. This gene, which we refer to as FLA, is located at one end of chromosome 4 between RFLP markers 506 and 3843 and is thus distinct from previously mapped genes that affect flowering time. The extreme delay in flowering time caused by the FLA gene can be overcome by vernalization in both the ecotypes in which it occurs naturally and in the Columbia ecotype into which this gene has been introgressed. PMID- 8455553 TI - Cloning and expression of the UGA4 gene coding for the inducible GABA-specific transport protein of Saccharomyces cerevisiae. AB - Transport of 4-aminobutyric acid (GABA) in Saccharomyces cerevisiae is mediated by three transport systems: the general amino acid permease (GAP1 gene), the proline permease (PUT4 gene), and a specific GABA permease (UGA4 gene) which is induced in the presence of GABA. The UGA4 gene encoding the inducible GABA specific transporter was cloned and sequenced and its expression analyzed. The predicted amino acid sequence shows that UGA4 encodes a 62 kDa protein having 9 12 putative membrane-spanning regions. The predicted UGA4 protein shares significant sequence similarity with the yeast choline transporter (CTR gene), exhibiting but limited similarity to the previously reported GABA transporters, i.e. the yeast GAP1 and PUT4 permeases and the rat brain GAT-1 transporter. Induction of UGA4 in the presence of GABA is exerted at the level of UGA4 mRNA accumulation, most probably at the level of transcription itself. This induction is conferred by the 5' flanking region and requires the integrity of two positive regulatory proteins, the inducer-specific factor UGA3 and the pleiotropic factor UGA35/DURL/DAL81. In the absence of the pleiotropic UGA43/DAL80 repressor, UGA4 is constitutively expressed at high level. PMID- 8455555 TI - Plasmid diversity in senescent and nonsenescent strains of Neurospora. AB - A sample of 171 natural isolates of Neurospora crassa and Neurospora intermedia was tested for senescence. Of these, 28 strains senesced within the duration of the experiment. These senescent strains, together with a selection of nonsenescent strains, were examined for the presence of mitochondrial plasmids. This was done by digesting mitochondrial DNA preparations with proteinase K, and running these samples on agarose gels. Most of the strains examined, both senescent and nonsenescent, contained plasmids, many of them new. Some new plasmids were linear, as inferred from their resistance to 5' exonuclease and sensitivity to 3' exonuclease. New circular plasmids were also found. Some strains carry several plasmids, and mixtures of circular and linear elements were common. A cross-homology study was performed on a sample of plasmid-bearing strains, and several cases of apparent relatedness were found, some between strains from distant geographical locations. Linear plasmids homologous to the maranhar linear senescence plasmid were quite common. A new member of the LaBelle circular plasmid homology group was found. In the sample tested for homology, no strains contained elements related to the kalilo linear senescence plasmid. The relationship of the new plasmids to senescence is not known. In addition to plasmid monomers, several different types of derivatives were found. The kalilo linear plasmid was found to occur in linear and circular forms of low mobility, presumed to be giant concatamers, and, in some strains, variant sibling structures and ladders of short derivatives were found. Circular plasmids also gave rise to extensive ladders on electrophoresis, probably representing different relaxation states and head-to-tail concatameric series. Some such forms migrated more slowly than mitochondrial DNA. One unique type of plasmid modification observed was a pair of linear elements that had apparently arisen de novo which showed homology to a circular plasmid. PMID- 8455556 TI - Molecular characterization of rgp2, a gene encoding a small GTP-binding protein from rice. AB - We previously reported the isolation of rgp1, a gene from rice, which encodes a ras-related GTP-binding protein, and subsequently showed that the gene induces specific morphological changes in transgenic tobacco plants. Here, we report the isolation and characterization of an rgp1 homologue, rgp2, from rice. The deduced rgp2 protein sequence shows 53% identity with the rice rgp1 protein, but 63% identity with both the marine ray ora3 protein, which is closely associated with synaptic vesicles of neuronal tissue, and the mammalian rab11 protein. Conservation of particular amino acid sequence motifs places rgp2 in the rab/ypt subfamily, which has been implicated in vesicular transport. Northern blot analysis of rgp1 and rgp2 suggests that both genes show relatively high, but differential, levels of expression in leaves, stems and panicles, but low levels in roots. In addition, whereas rgp1 shows maximal expression at a particular stage of plantlet growth, rgp2 is constitutively expressed during the same period. Southern blot analysis suggests that, in addition to rgp1 and rgp2, several other homologues exist in rice and these may constitute a small multigene family. PMID- 8455557 TI - Sequence analysis and interposon mutagenesis of a sensor-kinase (DctS) and response-regulator (DctR) controlling synthesis of the high-affinity C4 dicarboxylate transport system in Rhodobacter capsulatus. AB - A two-component sensor-regulator system has been identified in the purple photosynthetic bacterium Rhodobacter capsulatus, which controls the expression of high-affinity C4-dicarboxylate transport activity in these cells. Nucleotide sequencing has revealed the existence of two genes, dctS and dctR, which together form an operon linked to, but divergently transcribed from, the previously identified dctP gene, which encodes the periplasmic binding protein of the transport system. The DctS protein is predicted to be a membrane-bound sensor kinase with two potential membrane-spanning sequences in the N-terminal region. DctR was found to have sequence similarity throughout its entire length with proteins in the FixJ subfamily of response-regulators, especially to FixJ itself (42% identical residues). Insertional inactivation of the dctS and dctR genes resulted in the inability of the resulting mutants to grow on or transport malate, succinate or fumarate under aerobic conditions in the dark, and such mutants did not express the DctP protein. The mutants were complemented in trans by plasmids containing intact copies of the dctS and dctR genes. PMID- 8455558 TI - Isolation and characterization of a yeast gene that is homologous with a meiosis specific cDNA from a plant. AB - By using as probe a meiosis-specific cDNA clone LIM15 from the monocotyledonous plant, Lilium longiflorum, a clone containing a 2.8 kb DNA fragment was isolated from a genomic library of Saccharomyces cerevisiae. Primary structure analysis revealed that the clone includes two complete open reading frames, designated ISC2 and ISC10, capable of coding for a 36.6 kDa and a 31.6 kDa polypeptide, respectively, with the former frame being interrupted by a 92 bp intron. The predicted amino acid sequence of Isc2 was 56% identical with the putative gene product of lily cDNA clone LIM15, and showed limited sequence similarity with the yeast RAD57 gene product. Transcripts of the two genes begin accumulating 2.5 h and 7.5 h after induction of meiosis, respectively, according to a Northern hybridization analysis. Since disruption of either one of these genes had a drastic effect on the ability to form spores, ISC2 and ISC10 are expected to play significant roles in the formation of reproductive cells. PMID- 8455559 TI - Identification of an essential Drosophila gene that is homologous to the translation initiation factor eIF-4A of yeast and mouse. AB - A gene encoding a protein homologous to the translation initiation factor eIF-4A in mouse has been identified in Drosophila melanogaster. The predicted amino acid sequence shows 73% identity with the mouse gene and 67% identity with a homologous protein from yeast. The single-copy Drosophila gene is located on chromosome arm 2L at 26A7-9. Several recessive lethal mutations have been isolated and genetically characterized. Northern blot hybridization shows two abundant transcripts of 1.75 kb and 1.9 kb throughout all developmental stages. Both transcripts are maternally provided to the oocyte. PMID- 8455560 TI - Aspergillus nidulans nuclear proteins bind to a CCAAT element and the adjacent upstream sequence in the promoter region of the starch-inducible Taka-amylase A gene. AB - Aspergillus nidulans was used as an intermediate host to investigate the regulation of the Taka-amylase A (TAA) gene from Aspergillus oryzae. The induction of Taa by starch was confirmed to be regulated at the transcriptional level by analyzing the transcripts specific for Taa synthesized in vitro in nuclei from starch- and glucose-grown cells. A 55 bp DNA fragment containing a consensus CCAAT sequence from the promoter region of the Taa gene was shown to confer starch inducibility on the gene. A nuclear extract from starch-grown cells was assayed for proteins which bind to the promoter region of the Taa gene. A protein designated AnCP1 bound to the CCAAT sequence. A nuclear extract from glucose-grown cells contained two DNA-binding proteins designated AnCP2 and AnNP1. AnCP2 bound to the same CCAAT sequence as AnCP1, while AnNP1 bound to the 25 bp region just upstream of the AnCP2 binding site. Occupancy of the two binding sites appeared to be mutually exclusive, which is suggestive of a negative regulatory mechanism for gene expression. PMID- 8455561 TI - Characterization of the promoter from the single-copy gene encoding ferredoxin NADP(+)-oxidoreductase from spinach. AB - We describe a genomic DNA segment from spinach that bears part of the single-copy gene for ferredoxin-NADP(+)-oxidoreductase (FNR) including a 3.4 kb promoter sequence. Dissection of this DNA segment and its analysis in GUS (beta glucuronidase) gene fusions in transgenic tobacco demonstrated that the promoter differs in structure from all other promoters for thylakoid protein genes studied to date. Two regions with light-responsive elements were identified. One is located within the first 118 bp upstream of the transcription initiation site. A second fragment covering nucleotide positions -220 to -119 is capable of conferring light-dependent GUS gene expression on two different minimal promoters. The latter fragment binds a transacting factor in gel-shift assays. None of the fragments carries cis elements known from other genes to be involved in light-controlled expression. Comparison of the light responsiveness of GUS gene fusions controlled by the -753/+231 and -118/+231 regions indicates that they respond differentially to phytochrome-dependent signals and that their expression in tobacco is not restricted to tissue with functional chloroplasts. PMID- 8455563 TI - Three different types of organization of the vir regulon in group A streptococci. AB - The DNA of group A streptococci (GAS) encodes several important virulence factors such as the antiphagocytic M protein, the Ig-Fc-binding M-related proteins (FcrA like and EnnX-like) and the complement factor-inactivating C5a peptidase. The corresponding genes emm, fcrA, ennX, and scpA, respectively, were assumed to be located close together in the GAS genome. Additionally, emm and scpA have been found to be under the positive, coordinate control of the virR locus, which led to the designation "vir regulon" for the corresponding genomic segment. In order to map the vir regulons of many GAS serotypes and to analyse any correlation between the organization of vir regulons and circumscribed heterogeneities within the emm, virR, and scpA genes, an approach using several distinct sets of polymerase chain reaction (PCR) experiments was chosen. By examination of the genomic DNA of 42 GAS isolates from 36 different M serotypes three patterns of vir regulon topography were found. The first, designated "large vir regulon" (LVR), consists of virR--fcrA(-like)--emm--ennX(-like)--scpA. The second, designated "small vir regulon" (SVR), contains virR--emm--scpA, and the last, designated "unusual vir regulon" (UVR), resembles SVR but contains additional heterogeneous sequences between emm and scpA. The patterns correlate with heterogeneities at the 3' ends of the virR and scpA genes, with the M classification system and the occurrence of specific non-coding intervening sequences within the vir regulons. The potential impact of these patterns on models to account for generation of vir regulons is discussed. PMID- 8455562 TI - Integration host factor (IHF) modulates the expression of the pyrimidine-specific promoter of the carAB operons of Escherichia coli K12 and Salmonella typhimurium LT2. AB - We report the identification of Integration Host Factor (IHF) as a new element involved in modulation of P1, the upstream pyrimidine-specific promoter of the Escherichia coli K12 and Salmonella typhimurium carAB operons. Band-shift assays, performed with S-30 extracts of the wild type and a himA, hip double mutant or with purified IHF demonstrate that, in vitro, this factor binds to a region 300 bp upstream of the transcription initiation site of P1 in both organisms. This was confirmed by deletion analysis of the target site. DNase I, hydroxyl radical and dimethylsulphate footprinting experiments allowed us to allocate the IHF binding site to a 38 bp, highly A+T-rich stretch, centred around nucleotide -305 upstream of the transcription initiation site. Protein-DNA contacts are apparently spread over a large number of bases and are mainly located in the minor groove of the helix. Measurements of carbamoyl-phosphate synthetase (CPSase) and beta-galactosidase specific activities from car-lacZ fusion constructs of wild type or IHF target site mutants introduced into several genetic backgrounds affected in the himA gene or in the pyrimidine-mediated control of P1 (carP6 or pyrH+/-), or in both, indicate that, in vivo, IHF influences P1 activity as well as its control by pyrimidines. IHF stimulates P1 promoter activity in minimal medium, but increases the repressibility of this promoter by pyrimidines. These antagonistic effects result in a two- to threefold reduction in the repressibility of promoter P1 by pyrimidines in the absence of IHF binding. IHF thus appears to be required for maximal expression as well as for establishment of full repression. IHF could exert this function by modulating the binding of a pyrimidine-specific regulatory molecule. PMID- 8455564 TI - Donation: a new, facile method of gene replacement in yeast. AB - We describe here a new method for the introduction of non-selectable alleles into Saccharomyces cerevisiae, gene replacement by donation. This method only requires the availability of an autonomously replicating, selectable plasmid containing the allele to be introduced into yeast. The plasmid is digested at a restriction site (or sites) within this allele, and introduced into yeast by transformation. In the course of double-strand break repair, the entering plasmid donates genetic information to the chromosome, replacing the chromosomal allele in a gene conversion-like event. Gene replacement events are identified by a phenotypic screen of the transformants. When necessary, the transforming plasmid may be subsequently lost by segregation during permissive growth. We have studied several parameters affecting the utility of this protocol as a method of gene replacement. Together with our previous results, the results show gene replacement by donation to be a useful, facile method, yielding gene replacement in up to 1.5% of transformants. PMID- 8455565 TI - Somatic homologous recombination in planta: the recombination frequency is dependent on the allelic state of recombining sequences and may be influenced by genomic position effects. AB - We have previously described a non-selective method for scoring somatic recombination in the genome of whole plants. The recombination substrate consists of a defective partial dimer of Cauliflower Mosaic Virus (CaMV) sequences, which can code for production of viable virus only upon homologous recombination; this leads to disease symptoms on leaves. Brassica napus plants (rapeseed) harbouring the recombination substrate as a transgene were used to examine the time in plant development at which recombination takes place. The analysis of three transgene loci revealed recombination frequencies specific for each locus. Recombination frequencies were increased if more than one transgene locus was present per genome, either in allelic (homozygosity of the transgene locus) or in non-allelic positions. In both cases, the overall recombination frequency was found to be elevated to approximately the sum of the frequencies for the individual transgene loci or slightly higher, suggesting that the respective transgene loci behave largely independently of each other. For all plants tested (single locus, two or multiple loci) maximal recombination frequencies were of the order of 10(-6) events per cell division. PMID- 8455566 TI - Cis-regulatory sequences leading to female-specific expression of yolk protein genes 1 and 2 in the fat body of Drosophila melanogaster. AB - The three yolk protein genes (yp) of Drosophila melanogaster are transcribed in a sex- and tissue-limited fashion. We have searched for cis-regulatory sequences in regions flanking yp1 and yp2 to identify the elements that confer female-specific expression in the fat body. One such 127 bp element has previously been identified in this region. We show here the existence of two additional regions which confer female fat body-specific expression on an Adh reporter gene and on the native yp2 gene, respectively. This suggests some redundancy in the regulation of expression of the yp genes. Computer searches for putative binding sites for the DSX protein, which regulates sex-specific expression of the yp genes, revealed several such sites in our constructs. However, the significance of these is unclear since many such sites also occur in genes which one would not expect to be regulated in a sex-specific manner (e.g. Adh, Actin 5C). We suggest that DSX acts in concert with other proteins to mediate sex- and tissue-specific expression of the yp genes. PMID- 8455567 TI - Molecular analysis of the Septoria nodorum beta-tubulin gene and characterization of a benomyl-resistance mutation. AB - The complete nucleotide sequence of a benomyl-resistant allele of the Septoria nodorum beta-tubulin gene (tubAR) has been determined including 745 and 1024 nucleotides 5' and 3' to the tubAR coding region, respectively. tubAR encodes a 447 amino acid polypeptide which shows a high degree of homology with other fungal beta-tubulins. The gene contains three introns at codons 4, 12 and 53, uses 48 of the possible 61 sense codons and has a GC content of 59.1% in its coding region. S1 nuclease mapping has identified two transcriptional start sites 80 bp and 83 bp upstream of the translation start, and a transcriptional termination site 192 bp downstream of the stop codon. The two transcriptional start sites lie just 8 bp and 5 bp downstream of a CT motif consisting of 18 pyrimidine nucleotides interrupted by a single adenine. The wild-type allele tubA+ has been cloned using the polymerase chain reaction and the mutation producing the benomyl-resistant phenotype of tubAR mapped to a C to T transition at the first position of codon 6, resulting in a histidine to tyrosine amino acid substitution. PMID- 8455568 TI - In vivo definition of the functional origin of replication (ori(+)) of the promiscuous plasmid pLS1. AB - We have defined the minimal origin of replication of the plasmid pLS1 leading strand, as comprised within a 247 bp region, by in vivo deletion analyses. Cloning of pLS1 DNA regions containing its oriV(+) into a compatible replicon resulted in weak incompatibility towards pLS1, but only when the cloned fragment included the entire pLS1 oriV(+). Plasmids lacking a functional repB gene (which encodes the pLS1 initiator of replication RepB protein) could be established in Streptococcus pneumoniae only when RepB was supplied in trans. We conclude that all the pLS1-encoded gene products involved in its replication and control are efficient trans-complementing plasmid elements. PMID- 8455569 TI - DNA addition or deletion is associated with a major karyotype polymorphism in the fungal phytopathogen Colletotrichum gloeosporioides. AB - A 1.2 Mb minichromosome resolved by pulsed-field electrophoresis was present in two independent race 3 isolates of Colletotrichum gloeosporioides causing Type B anthracnose specifically on Stylosanthes guianensis cv. Graham in Australia. This chromosome was absent in duplicate isolates representing races 1, 2 and 4 which infect other S. guianensis cultivars. A gene library was prepared specifically from the 1.2 Mb minichromosome and ten independent DNA clones unique to this chromosome were identified by differential hybridisation to whole chromosome probes. All of the ten selected probes hybridised only to the 1.2 Mb minichromosome unique to the race 3 isolates but not to any chromosome in isolates of the other races. These ten probes also hybridised only to restriction digested DNA of race 3 and were thus both chromosome- and strain-specific for Type B C. gloeosporioides. Hybridisation analysis of NotI fragments of the 1.2 Mb minichromosome with these sequences indicated that they were not tightly clustered on the chromosome. These data demonstrate that the variation in the occurrence of the 1.2 Mb minichromosome did not arise by rearrangement of the genome of a progenitor strain but involved either large scale deletion or addition of DNA. The 1.2 Mb minichromosome did not contain a cloned high-copy number repeat sequence present on all other mini- and maxichromosomes, suggesting addition from a genetically distinct strain. All ten chromosome-specific DNA probes hybridised to a 2.0 Mb chromosome in all races of C. gloeosporioides causing Type A anthracnose on Stylosanthes spp. including S. guianensis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455570 TI - Autoregulation by cooperative binding of the PemI and PemK proteins to the promoter region of the pem operon. AB - The low copy number plasmid R100 carries the pem region, consisting of two genes, pemI and pemK, which are required for stable maintenance of the plasmid. Here, to understand the regulation of the expression of the pem region, we constructed plasmids carrying either the pemI or the pemK gene, whose initiation codons were fused in frame with the lacZ gene, and examined their expression by assaying beta galactosidase (LacZ) activity. The synthesis of both PemI and PemK proteins was found to be repressed coordinately in the presence of a plasmid carrying the entire pem region. This indicates that pemK and pemI cistrons form an operon, and that the expression of the operon is negatively regulated by its own products. We then conducted a gel retardation assay in vitro and found that the two pem products, each of which was obtained as a tripartite protein (PemI-collagen-LacZ and PemK-collagen-LacZ), bound cooperatively to a specific fragment containing the proximal region of the pem operon. The binding region, determined by DNase I footprinting analysis, included the promoter for the pem operon. This indicates that both PemI and PemK proteins bind to the promoter region to autoregulate their synthesis. PMID- 8455571 TI - Cloning of the phycobilisome rod linker genes from the cyanobacterium Synechococcus sp. PCC 6301 and their inactivation in Synechococcus sp. PCC 7942. AB - The phycobilisome rod linker genes in the two closely related cyanobacteria Synechococcus sp. PCC 6301 and Synechococcus sp. PCC 7942 were studied. Southern blot analysis showed that the genetic organization of the phycobilisome rod operon is very similar in the two strains. The phycocyanin gene pair is duplicated and separated by a region of about 2.5 kb. The intervening region between the duplicated phycocyanin gene pair was cloned from Synechococcus sp. PCC 6301 and sequenced. Analysis of this DNA sequence revealed the presence of three open reading frames corresponding to 273, 289 and 81 amino acids, respectively. Insertion of a kanamycin resistance cassette into these open reading frames indicated that they corresponded to the genes encoding the 30, 33 and 9 kDa rod linkers, respectively, as judged by the loss of specific linkers from the phycobilisomes of the insertional mutants. Amino acid compositions of the 30 and 33 kDa linkers derived from the DNA sequence were found to deviate from those of purified 33 and 30 kDa linkers in the amounts of glutamic acid/glutamine residues. On the basis of similarity of the amino acid sequence of the rod linkers between Synechococcus sp. PCC 6301 and Calothrix sp. PCC 7601 we name the genes encoding the 30, 33 and 9 kDa linkers cpcH, cpcI and cpcD, respectively. The three linker genes were found to be co-transcribed on an mRNA of 3700 nucleotides. However, we also detected a smaller species of mRNA, of 3400 nucleotides, which would encode only the cpcH and cpcI genes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455572 TI - Mitochondrial DNA deletion in human myocardium. AB - Mutation of myocardial mitochondrial DNA was investigated in human left ventricles obtained at autopsy using the polymerase chain reaction (PCR). Seventeen autopsy cases were examined, including patients with diabetes mellitus, myocardial infarction, cardiomyopathy, cancer, and other diseases. Two cases of diabetes mellitus, 2 of myocardial infarction, and 1 of pulmonary fibrosis showed a 7.4 kb deletion of myocardial mitochondrial DNA. Primer shift PCR confirmed that an amplified DNA fragment had not been obtained by misannealing of the primers. It is unclear how much these findings are related to the severity or prognosis of the various diseases, but they indicate that mutation of myocardial mitochondrial DNA can occur in other diseases besides cardiomyopathy, although the influence of aging could not be excluded. PMID- 8455573 TI - Ischemic changes in myocardial ionic contents of the isolated perfused rat hearts as studied by NMR. AB - Using 31P-, 23Na- and 39K-NMR, we assessed ischemic changes in high energy phosphates and ion contents of isolated perfused rat hearts continuously and systematically. To discriminate intra- and extracellular Na+, a shift reagent (Dy(TTHA)3-) was used in 23Na-NMR study. In 39K-NMR study, the extracellular K+ signal was suppressed by inversion recovery pulse sequence in order to obtain intracellular K+ signal without using shift reagents. During the early period of ischemia, increases in intracellular Na+ and inorganic phosphate (Pi) were observed in addition to the well-documented decreases in creatine phosphate and ATP and a fall of intracellular pH, suggesting an augmented operation of Na(+)-H+ exchange triggered by a fall of the intracellular pH resulted from breakdown of ATP. At around 15 min of ischemia, a second larger increase in intracellular Na+ and a decrease in intracellular K+ were observed in association with a second increase in Pi. This was accompanied by an abrupt rise of the ventricular end diastolic pressure. As there was a depletion of ATP at this time, the increase in intracellular Na+ and associated decrease in intracellular K+ may be explained by inhibition of the Na(+)-K+ ATPase due to the depletion of ATP. A longer observation with 31P-NMR revealed a second phosphate peak (at lower magnetic field to ordinary Pi peak) which increased its intensity as ischemic time lengthened. The pH of this 2nd peak changed in parallel with the changes in pH of the bathing solution, indicating the appearance of a compartment whose hydrogen concentration is in equilibrium with that of the external compartment. Thus, the peak could be used as an index of irreversible membrane damage of the myocardium. PMID- 8455574 TI - 31P-NMR magnetization transfer study of reperfused rat heart. AB - The relationships between pressure rate product (PRP) and flux (PCr-->ATP) or flux(Pi-->ATP) were studied in isolated perfused rat hearts by the method of saturation transfer using 31P-NMR during the preischemic and reperfusion periods. The hearts were made ischemic for 15 min, followed by 60 min of reperfusion. PRP was almost completely depressed, and recovered to 60% of the control level (preischemic period) after reperfusion. The ATP level during reperfusion was significantly decreased, whereas there was no significant change in PCr level. Pi level of reperfused hearts was significantly higher than that in the control. Both flux(PCr-->ATP) and flux(Pi-->ATP) were significantly decreased during the reperfusion period (both p < 0.05). However, the flux(PCr-->ATP)/PRP ratio during reperfusion did not differ from that of the control. This result indicates that the decrease in flux(PCr-->ATP) was matched by a similar decrease in cardiac performance. In contrast, the flux(Pi-->ATP)/PRP ratio during reperfusion was significantly decreased compared to that of control. These results suggest that the stunned heart needs less ATP turnover in proportion to its depressed contractile activity, and flux(Pi-->ATP) may lmit the recovery of postischemic performance. PMID- 8455575 TI - Release of 6-keto-PGF1 alpha and thromboxane B2 in late appearing cardioprotection induced by the stable PGI analogue: 7-OXO-PGI. AB - We have shown earlier that prostacyclin (PGI2) and its stable analogue: 7-oxo prostacyclin(7-OXO) may induce a prolonged, late appearing (24-48 h after drug administration), dose dependent protection of the heart from harmful consequences of a subsequent severe ischaemic stress, such as myocardial ischaemia, life threatening ventricular arrhythmias and early ischaemic morphological changes. In an other study we observed that a similar but shortlived (less than 1 h) cardioprotection, induced by 'preconditioning' brief coronary artery occlusions, is greatly reduced by blockade of the cyclooxygenase pathway, suggesting that prostanoids might play a role in this shortlasting protection. Objective of our present study was to elucidate the importance of some arachidonic acid (AA) metabolites, such as PGI2 and thromboxane A2 (TXA2) in the mechanism of the late appearing, prolonged cardioprotection. Estimation of the metabolites: 6-keto-PGF1 alpha (6-KETO) and thromboxane B2 (TXB2) was made from the perfusate of isolated Langendorff hearts of guinea-pigs pretreated with 50 micrograms/kg 7-OXO, 24 and 48 h before preparation. Pretreatment alone produced a slight, but significant elevation of 6-KETO (from 206 +/- 11 to 284 +/- 19 pg/ml/min after 24 h, and to 261 +/- 18 pg/ml/min after 48 h). No change was seen in TXB2 production. Global ischaemia for 25 min (followed by 25 min reperfusion) markedly increased the release of both AA metabolites; maximal values were observed in the third min of reperfusion (6-KETO from 206 +/- 11 to 1275 +/- 55 pg/ml/min and TXB2 from 29 +/- 4 to 172 +/- 12 pg/ml/min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455576 TI - Cardioprotective actions of wild garlic (allium ursinum) in ischemia and reperfusion. AB - The susceptibility to ventricular arrhythmias under the conditions of cardiac ischemia and reperfusion was investigated in the Langendorff heart preparation of rats fed for eight weeks a standard chow enriched with 2% of pulverized wild garlic leaves. The isolated hearts were perfused with a modified Krebs-Henseleit solution. The incidence of ventricular fibrillation (VF) during 20 min occlusion of the descending branch of the left coronary artery (LAD) was significantly reduced in the wild garlic group as compared to untreated controls (20% vs 88%). The same holds for the size of the ischemic zone (33.6% vs 40.9% of heart weight). In the reperfusion experiments (5 min after 10 min ischemia), ventricular tachycardia (VT) occurred in 70% of the wild garlic group vs 100% in untreated controls and VF in 50% vs 90%. The time until occurrence of extrasystoles, VT or VR was prolonged. No significant alterations in cardiac fatty acid composition could be observed. Although the prostacyclin production was slightly increased in hearts of the wild garlic group, inhibition of cyclooxygenase by acetylsalicylic acid (ASA; aspirin) could not completely prevent the cardioprotective effects suggesting that the prostaglandin system does not play a decisive role in the cardioprotective action of wild garlic. Furthermore, a moderate angiotensin converting enzyme (ACE) inhibiting action of wild garlic was found in vitro as well as in vivo that could contribute to the cardioprotective and blood pressure lowering action of wild garlic. Whether a free radical scavenging activity of wild garlic is involved in its cardioprotective effects remains to be established. PMID- 8455577 TI - Effects of a new class I antiarrhythmic drug bidisomide on canine ventricular arrhythmia models. AB - The antiarrhythmic and direct cardiovascular effects of a new antiarrhythmic agent, bidisomide, alpha-(2-[acetyl(1-methylethyl)amino]ethyl)-alpha-(2- chlorophenyl)-1-piperidinebutanamide, were investigated. To determine the anti arrhythmic effects, spontaneously occurring adrenaline-, digitalis- and two-stage coronary ligation-induced arrhythmias were used. Bidisomide suppressed these three arrhythmia models. The antiarrhythmic plasma concentration, IC50, of bidisomide for digitalis-induced arrhythmia was 22.1 micrograms/ml, and those calculated for intravenous bidisomide in 24 h and 48 h coronary ligation arrhythmias were 15.1 and 11.6 micrograms/ml and that calculated for oral bidisomide in 24 h coronary ligation-arrhythmia was 5.4 micrograms/ml and that for adrenaline induced arrhythmia was 58.7 micrograms/ml. In the blood perfused sinoatrial node and papillary muscle preparations, bidisomide decreased the sinoatrial rate and contractile force and increased the intraventricular conduction time and coronary blood flow. These results indicate that bidisomide is similar to other class I antiarrhythmic agents such as pirmenol and KW-3401 in its antiarrhythmic profile and is expected to become a clinically useful antiarrhythmic drug. PMID- 8455578 TI - Growth factor for cardiac hypertrophy. AB - Cardiac size can be regulated by the balance in activity between cardiac growth factors and inhibiting factors, chalones. This study was undertaken to verify the role of the cardiac growth factor and its purification from hypertrophied hearts. For this propose the hypertrophied hearts of renovascular hypertensive rats were used. The purification was made by using an isoelectric focusing chromatography and the HPLC method. We examined the cardiac growth effect of the isolated fractions with cultured chicken embryonic cardiac myocytes. Simultaneously, the influence of these fractions on the cardiac cell cycle was examined by DNA analysis with the flow cytometric method. If the hearts were overloaded due to hypertension, the growth of the cardiac size could be induced by increased the level of five proteins with different molecular weight and with an isoelectric point of 8.3. The significant growth activities were observed at these five proteins compared to the absence of the fractions. For the appearance of these growth effect, it is necessary that the structure of the protein is there fundamentally as a form with a molecular weight of 27 k dalton. After addition of these isolated fractions, BrdU content is S and G2 phases by flow cytometry was increased. This change indicates that the cardiac myocytes are stimulated in form DNA synthesis. PMID- 8455579 TI - Antimicrobial activity of lipoprotein particles containing apolipoprotein Al. AB - Human plasma in vitro inhibits the growth of coagulase negative staphylococci, S. epidermidis, which may be pathogenic in the immunocompromised host. To determine the antimicrobial components, serum was fractionated by column chromatography, which revealed that elution areas where lipoproteins can be yielded had high antimicrobial activity against S. epidermidis. Therefore, lipoprotein fractions, including very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL), were separated by ultracentrifugation and incubated with S. epidermidis. All 3 lipoprotein fractions suppressed bacterial growth within the first 3 h but VLDL enhanced bacterial growth after 9 h of incubation compared with the control. HDL, however, inhibited bacterial growth throughout 21 h of incubation. To confirm these results, serum from healthy volunteers was separated by ion exchange column chromatography and again by HPLC to purify the antimicrobial fraction. In the protein analysis with gradient polyacrylamide-SDS gel, apolipoprotein Al (apo Al), which is a major apolipoprotein of HDL, was detected in the antimicrobial fraction. Therefore, this fraction was loaded onto an immunoaffinity column coupled with the anti-apo Al monoclonal antibody (Mab). Unbound fraction had no antimicrobial activity, but anti-S. epidermidis activity was recovered from the bound fraction which consisted mainly of apo Al, All and apo C in protein composition. These results indicated that the antimicrobial activity was associated with the apo Al containing lipoprotein particles (HDL). This property of HDL may directly affect bacterial growth and promote the self-defense mechanisms of normal and immunocompromised individuals. PMID- 8455580 TI - Molecular characteristics in Japanese patients with lipidosis: novel mutations in metachromatic leukodystrophy and Gaucher disease. AB - The characterization of mutations in Japanese patients with lipidosis, particularly in metachromatic leukodystrophy (MLD) and Gaucher disease has been studied in detail. Metachromatic leukodystrophy is characterized by an accumulation of sulfatide in nervous tissues and kidney due to a deficiency of arylsulfatase A (ASA). We analyzed the presence of three known mutant arylsulfatase A alleles in Japanese patients with MLD. Among 10 patients of Japanese patients with MLD, we found that allele 445A mutation has moderately high incidence and also homozygosity of this mutation results in the late infantile form. Allele 2381T was not found in Japanese patients. Furthermore, we found novel mutation which is G- to A mutation at the 1070 nucleotide of the ASA gene (designated 1070 A) in Japanese patients with juvenile onset. This mutation results in a amino acid substitution of Gly245 by Arg and found in heterozygote form. Our studies of molecular analysis in 10 Japanese patients with MLD indicate that Japanese MLD patients have unique characteristics of ASA mutations compared with those of Caucasian patients. On the other hand, Gaucher disease is the most prevalent sphingolipidosis, characterized by an accumulation of glucocerebroside in macrophage derived cells due to a deficiency of lysosomal hydrolase glucocerebrosidase. To study the molecular basis of Gaucher disease in Japanese patients, we analyzed the presence of the two known mutations (6433C and 3548A) in the glucocerebrosidase gene of 15 patients with Gaucher disease. We found that the 6433C and 3548A mutations occur in all subtypes of Japanese patients with Gaucher disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455581 TI - Modulation of the effect of glibenclamide on KATP channels by ATP and ADP. AB - The inside-out configuration of the patch-clamp technique was used to study the effect of glibenclamide on the ATP-sensitive K+ channel current in isolated guinea-pig ventricular myocytes. The inhibitory effect of glibenclamide was tested in the bath solution containing two different concentrations of ATP (100 microM and 200 microM). It was found that the effect of the drug on the KATP current was stronger in the presence of the higher concentration of ATP. The blocking effect of glibenclamide on the channels was weaker if, in addition to ATP, ADP was applied in the intracellular solution. Similarly, the inhibitory effect of the drug was not pronounced for the channels reactivated by ADP after run-down. As application of the drug in the presence and absence of Mg2+ did not show different effects on the channel inhibition, we concluded that the effect of glibenclamide may not depend on the phosphorylation of the channel protein. These results suggest that in addition of the previously described effect of ADP, ATP also has some modulatory effect on inhibition of the KATP channel by glibenclamide. PMID- 8455582 TI - Differing responses of G2-related genes during differentiation of HL60 cells induced by TPA or DMSO. AB - Differentiation leads to the cessation of cellular proliferation, but little is known about the molecular mechanisms of growth arrest. We compared the effect of two differentiation inducers, 12-o-tetradecanoyl 13-acetate (TPA) and dimethyl sulfoxide (DMSO) on both the cell-cycle and the modulation of G2-related genes in synchronized HL60 cells. TPA treatment of HL60 cells resulted in G1 arrest within 24 h. In contrast, the cell cycling of DMSO-treated cells was initially accelerated and they progressed to the second cycle before accumulating in the G1 phase. Expression of cyclin B, cdc25, wee1 and cdc2 was studied during cell cycle arrest by Northern blot hybridization. Expression of cyclin B, cdc25 and cdc2 fluctuated in association with cell cycle progression towards the G2/M phase, while wee1 expression remained constant in untreated cells. These four genes were highly expressed in TPA-treated cells for the first 12 h, but drastic down regulation was seen at 18 h and expression became undetectable after 24 h. In contrast, no remarked changes of gene expression were seen in DMSO-treated cells. These findings suggest that cell cycle progression along with the initial process of differentiation in response to TPA differs from the response to DMSO and that the down-regulation of cdc2 expression by TPA-treated HL60 cells contributes to endorsement of G1 arrest. PMID- 8455583 TI - Control of growth in neonatal pig hearts. AB - The pig heart grows at a maximal rate in the first 2-3 days of life due to a volume overload imposed on the heart at birth. Rates of ribosome formation and protein synthesis cannot be further accelerated during in vitro perfusion with agents that increase cyclic AMP, that bind to alpha 1-adrenergic receptors or that bind to angiotensin II receptors. Growth of the heart in vivo can be restrained by treatment with an angiotensin-converting enzyme inhibitor, enalapril maleate, or an angiotensin receptor antagonist, DuP 753. In the enalapril-treated heart, norepinephrine plus propranolol, but not angiotensin II, accelerated ribosome formation. Rapid growth of the left ventricle of pig heart during the first 10 days of life is due largely to eccentric hypertrophy. PMID- 8455584 TI - Mechanistic effects of kijimicin on inhibition of human immunodeficiency virus replication. AB - Kijimicin represents an important type of ionophore compound. In veterinary medicine, it is becoming important as anticoccidiostatic agent and feed supplement. We examined Kijimicin for its HIV inhibitory activity. The compound exhibited concentration-dependent inhibition of HIV replication in primary infected cultures of human T-lymphoblastoid H9 cells. Substantial inhibition of viral replication was observed at concentrations of Kijimicin that showed little cytotoxicity. The ratio of IC50 values for the MTT to RT assays was 40. Anti HIV activity was also observed in cultures of monocytic lineage U937 cells chronically infected with HIV. Moreover, in attempting to define the inhibitory mechanism of Kijimicin, we investigated its effect on each step of HIV replication. The infectivity of progeny viral particles was reduced by Kijimicin treatment. This decrease may be due to incompletely glycosylated forms of gp120. PMID- 8455585 TI - Function and energy metabolism of isolated hearts obtained from hyperthyroid spontaneously hypertensive rats (SHR). A 31P-nuclear magnetic resonance study. AB - It was the aim of this study to evaluate the effects of hyperthyroidism on heart function and cardiac energy metabolism of spontaneously hypertensive (SHR) rats. Hyperthyroidism was induced by daily injections of T3 (0.2 mg/kg s.c.) for 14 days. The hearts were then isolated and perfused in the Langendorff mode. ATP, phosphocreatine (PCr), and inorganic phosphate (Pi) were measured continuously by means of 31P-nuclear magnetic resonance (NMR) spectroscopy. Work load was altered by varying stepwise the Ca++ concentration in the perfusion fluid from 0.5 to 1.0, 1.5, and 2.0 mM, respectively. At every elevation of the Ca++ concentration, the increase in left ventricular developed pressure (LVDP) was higher in the hyperthyroid SHR than in the untreated SHR hearts. The ATP and PCr concentrations were lower in the hyperthyroid SHR compared to the untreated SHR hearts throughout the perfusion period. PCr decreased at every Ca++ elevation in both the untreated and hyperthyroid SHR hearts. The PCr/ATP ratio was not altered at any Ca++ concentration neither in the untreated SHR nor in the hyperthyroid SHR hearts. The Ca(++)-induced stepwise elevation in LVDP was higher at any given PCr/Pi ratio in the hyperthyroid SHR than in the untreated SHR hearts. Thus, the Ca(++)-inducible contractile reserve was greater in the hyperthyroid SHR heart. PMID- 8455586 TI - Increased calcium release from sarcoplasmic reticulum stimulated by inositol trisphosphate in spontaneously hypertensive rat heart cells. AB - It is known that inositol (1, 4, 5)-trisphosphate (IP3) stimulates Ca2+ release from sarcoplasmic reticulum (SR) in several tissues, but in cardiac myocytes this phenomenon has not been confirmed. The purpose of the present study was to confirm the effect of (1, 4, 5)-IP3 on Ca2+ release from SR in cardiac myocytes. The effect of IP3 on Ca2+ release from SR in hypertrophic cardiac cells was also determined. We examined the effects of IP3 on Ca2+ release from cardiac myocyte SR by the digital-image method in a single cell. We also determined the effect of IP3 on calcium release from isolated SR. SR was prepared from spontaneous hypertensive rat hearts and Wistar kyoto rat hearts. The SR was prelabeled with 45Ca2+, and then incubated with the indicated concentrations of IP3 for 1 min at 37 degrees C. In cardiac myocytes treated with saponin, Ca2+ release stimulated by 10 microM (1, 4, 5)-IP3 was detected by fura-2. In 45Ca2+ prelabeled SR, the maximal Ca2+ release was achieved at 10 microM IP3 incubated for 1 min. The release of Ca2+ was higher in SR of SHR than in the SR of WKY. IP3 stimulates Ca2 release from cardiac SR, and this release is greater in SHR than in WKY. However, it is uncertain whether this phenomenon plays a role in cardiac hypertrophy. PMID- 8455587 TI - Radial spread of aequorin Ca2+ signal in single frog skeletal muscle fibers. AB - The Ca(2+)-sensitive photoprotein aequorin was injected into single frog skeletal muscle fibers, and the intracellular aequorin light intensity during muscle activation with different maneuvers was mapped with digital imaging microscopy. During 50 Hz electrical activation (tetanus), the aequorin light intensity from different locations in the muscle fiber rose with very similar time course. Caffeine (10 mM) application, on the other hand, caused aequorin light signals to show significantly different time courses, with an earlier increase in Ca2+ concentration near the surface of the fiber than near the core. The non-uniform rise of intracellular Ca2+ concentration with caffeine treatment is consistent with the slow inward diffusion of caffeine and subsequent Ca2+ release from sarcoplasmic reticulum. PMID- 8455588 TI - Cardiac contractile proteins and autoimmune myocarditis. AB - Concerning cardiac contractile proteins, antigenicity and myocardiotogenicity were discussed. In normal states, these proteins are immunologically tolerant, and can not provoke any heart-specific disease. Why the proteins can provoke such lethal autoimmune myocarditis has not been completely elucidated. Shortly after cardiac infection or myocardial ischemia, these proteins may work as the antigen for the autoimmune myocarditis. First of all, the role of cardiac myosin has been strongly emphasized. But, the antigen determinants: epitope proteins remain unclear. Either cross-activity to the streptococcal M protein and/or the alpha helical coiled-coil protein may be an important factor to determine antigenicity. In this autoimmune myocarditis, the roles of T-lymphocyte and cardiac dendritic cell are noticeable. Through further study on the relation between antigen epitope and the infectious agents in the heart; on cardio-cytotoxicity of the T lymphocyte and on the precise contribution of cardiac dendritic cells, this autoimmune myocarditis will be more clarified. PMID- 8455589 TI - Force-frequency-relation in human atrial and ventricular myocardium. AB - In human heart failure, an increase in frequency of stimulation is followed by a reduced force of contraction in vivo and in vitro. The present study aimed to investigate whether a different origin of the myocardial sample or pretreatment with the cardioprotective agent 2,3-butanedione-monoxime (BDM) influences the force-frequency-relationship in electrically driven muscle strips taken from failing and nonfailing human myocardium. With as well as without pretreatment with BDM, the altered force-frequency-relationship in failing compared to nonfailing human ventricular myocardium can be observed. The effectiveness and the potency to increase force of contraction following an increase in frequency of stimulation was significantly higher in atrial than in ventricular myocardium in nonfailing and failing tissue. The different observations in atrial and ventricular myocardium provide evidence for functionally relevant differences in the electromechanical coupling between the human atrial and ventricular myocardium. PMID- 8455590 TI - Depressed sliding velocity of isolated cardiac myosin from cardiomyopathic hamsters: evidence for an alteration in mechanical interaction of actomyosin. AB - We measured the relative sliding velocity of cardiomyopathic hamster cardiac myosin on actin cables by using an in vitro motility assay system. We also investigated the relationship between the velocity and both myosin isozyme content and ATPase activity. Cardiac myosin was obtained from cardiomyopathic hamsters (BIO 14.6; B) aged 3, 6, 9, and 18 months and age-matched controls (F1B; F). Long well-organized actin cables of an alga, Nitellopsis, were used for the motility assay. Small latex beads (2 microns in diameter) were coated with purified cardiac myosin. When myosin-coated beads were introduced into an algal cell in the presence of Mg-ATP, myosin interacted with actin and dragged the beads. Active movement of the beads along the actin cables was observed under a photomicroscope and the velocity was measured. The velocity was significantly lower in B than in F for each age group (0.47 vs. 0.71 microns/s at the age of 3 months, p < 0.05; 0.44 vs. 0.88 microns/s at 6 months, p < 0.01; 0.44 vs. 0.67 microns/s at 9 months, p < 0.01; 0.35 vs. 0.52 microns/s at 18 months, p < 0.05). Both Ca(2+)-activated ATPase activity and the percentage of alpha-myosin heavy chain were also lower in B than in F for each age group. When examined for individual specimens, there was a positive correlation between the velocity and both myosin Ca(2+)-activated ATPase activity (r = 0.84) and percentage of alpha myosin heavy chain (r = 0.83). These data points of both control and cardiomyopathic hamsters were distributed near the regression line obtained from control and thyroxine-treated rabbits reported previously. The present results indicate that the difference in mechanical properties between control and cardiomyopathic cardiac myosin is attributed to isozyme redistribution and not to a qualitative change in each myosin molecule. PMID- 8455591 TI - Abnormalities of ADP/ATP carrier protein in J-2-N cardiomyopathic hamsters. AB - ADP/ATP carrier protein (AAC) is located in the mitochondrial inner membrane and has an important function in mitochondrial energy supply. This protein transports ATP to the cytoplasm and counter transports ADP into the mitochondria. J-2-N cardiomyopathic hamsters were investigated to determine the AAC content in cardiac mitochondria. After recording an electrocardiogram and collecting blood, the cardiac mitochondria were isolated. The mitochondrial membranes were labelled with eosin-5-maleimide (EMA) and separated on SDS polyacrylamide gels. The position of the AAC component was identified by exposing the gel under UV light, and the AAC content was determined by densitometry after staining with Coomassie blue. The AAC content ratio was significantly decreased in both 10-week-old and 1 year survived J-2-N hamsters when compared to control Golden hamster. Among 10 week-old J-2-N hamsters, the decrease in the AAC content ratio was more marked for the animals with more severe myocardial damage. The H(+)-ATPase activities of mitochondrial membrane were higher in 10-week-old J-2-N hamsters than in control hamsters. These results suggest that the decrease of AAC in J-2-N hamster plays an important role in the pathogenesis of cardiomyopathy in J-2-N hamsters. PMID- 8455592 TI - Age-associated damage in mitochondrial DNA in human hearts. AB - Damage to mitochondrial DNA seems to be involved in the etiology of age associated degenerative diseases. The aim of this study is to elucidate effects of aging on human mitochondrial DNA. 8-Hydroxy-deoxyguanosine, a product of free radical damage to deoxyguanosine, is reported to cause random point mutations. In human mitochondrial DNA, 8-hydroxy-deoxyguanosine increased exponentially with age, and the population of mitochondrial DNA with deletion increased also exponentially with age. Furthermore, a clear correlation existed between the accumulation of 8-hydroxy-deoxyguanosine and that of mitochondrial DNA with deletion. We also determined the effects of aging on rat mitochondrial function together with 8-hydroxy-deoxyguanosine content in mitochondrial DNA. The activities of complexes I and IV of the mitochondrial electron transport chain decreased significantly in rats aged 100 weeks compared with those in rats aged 7 weeks. A concomitant increase in 8-hydroxy-deoxyguanosine was observed in mitochondrial DNA of rats aged 100 weeks. From our results, it is concluded that the age-associated accumulation of somatically acquired oxygen damage together with deletions in mitochondrial DNA might be important contributors to the deterioration of cardiac function associated with age. PMID- 8455593 TI - Characterization of a novel chicken heat shock transcription factor, heat shock factor 3, suggests a new regulatory pathway. AB - We have cloned three avian heat shock transcription factor (HSF) genes corresponding to a novel factor, HSF3, and the avian homologs of mammalian HSF1 and HSF2. The predicted amino acid sequence of HSF3 is approximately 40% related to the sequence of HSF1 and HSF2. The sequences for all three factors exhibit extensive identify in the DNA binding motifs and the heptad repeats of hydrophobic amino acids which are common to all eukaryotic HSFs. Despite these overall similarities, each avian HSF exhibits distinct DNA binding properties. HSF2 when expressed in vitro binds constitutively to the heat shock element promoter sequence, whereas neither HSF1 nor HSF3 expressed in vitro binds to DNA. HSF1 DNA binding is induced upon heat shock or treatment with nonionic detergents, whereas the DNA binding properties of HSF3 are not induced by these conditions in vitro. These results suggest that HSF3 activation may involve an induction pathway distinct from the traditional forms of heat shock gene induction. HSF3 DNA binding activity, however, is obtained when the carboxyl terminal region including the distal heptad repeat is deleted, indicating the presence of negative cis-regulatory sequences. The HSF3 message, like HSF1 and HSF2 messages, is coexpressed during development and in most tissues, which suggests a general role for the regulatory pathway involving HSF3. PMID- 8455594 TI - A retrovirus carrying the K-fgf oncogene induces diffuse meningeal tumors and soft-tissue fibrosarcomas. AB - The K-fgf/hst oncogene encodes a growth factor of the fibroblast growth factor (FGF) family and transforms cells through an autocrine mechanism which requires extracellular activation of its receptor(s). To identify the cell and tissue targets of K-fgf oncogenic potential in vivo, we constructed a recombinant retrovirus carrying the human K-fgf cDNA and injected it, together with helper Moloney murine leukemia virus, into immunocompetent as well as nude mice. The original construct was highly transforming in tissue culture but produced no detectable pathologies in vivo with the exception of a single fibrosarcoma which arose after a long latency. The virus produced by this tumor appears to have undergone a complex series of recombination events involving the helper Moloney murine leukemia virus. It encodes an Env/K-FGF fusion protein whose expression is under the control of a hybrid long terminal repeat. This virus (designated MFS, for meningeal fibrosarcoma) induces tumors in mice with high frequency and short latency. These neoplasms consist of aggressive fibrosarcomas of soft tissue as well as diffuse meningeal tumors originating from the dura mater that surround the whole central nervous system and cause severe hydrocephalus. The Env/K-FGF fusion protein expressed by the MFS virus has retained all of the biological properties of native K-FGF, including secretion, mitogenic activity, heparin binding, and neutralization by anti-K-FGF antibodies. These and other results indicate that the tumors induced by the MFS virus result from the oncogenic potential of K-FGF. PMID- 8455595 TI - The product of a novel growth factor-activated gene, fic, is a biologically active "C-C"-type cytokine. AB - We have characterized a new member of the superfamily of proinflammatory peptides encoded by a growth factor-inducible gene, fic, previously isolated by differential screening of a cDNA library of mRNA from serum-stimulated NIH 3T3 cells. Immunoprecipitation analyses showed that the protein was rapidly induced following serum stimulation and secreted unglycosylated into the medium. The fic protein, FIC, shows highest sequence homology (57%) to human and rabbit monocyte chemoattractant protein 1 (MCP-1), an established monocyte activator. To determine the biological activity of FIC and to compare it with that of mouse MCP 1 (muMCP-1), both proteins were expressed in the baculovirus system. FIC and muMCP-1 were purified to near homogeneity by a two-step chromatography protocol. Both proteins elicited changes in intracellular calcium concentration in human monocytes. The effect was dependent on external Ca2+ and was inhibited by pretreatment of cells with pertussis toxin. FIC did not desensitize human monocytes to the three related cytokines muMCP-1, human MCP-1 (huMCP-1), and huMCP-2. However, pretreatment with muMCP-1 or huMCP-1, but not with huMCP-2, desensitized human monocytes to FIC. Specific binding of [125I]FIC was found in human monocytes, mouse monocytic cultured cells, and human endothelial cells but not in lymphocytes, neutrophils, or primary mouse fibroblasts. Scatchard analysis of the binding of [125I]FIC to human monocytes showed the presence of two classes of receptors, with apparent KdS of 1.2 and 7.7 nM and receptor numbers per cell of 2,400 and 6,300, respectively. FIC, muMCP-1, and huMCP-1 competed to the same extent for the binding of [125I]FIC to human monocytes, contrary to huMCP-2, which competed very ineffectively, if at all. PMID- 8455596 TI - Characterization of sgk, a novel member of the serine/threonine protein kinase gene family which is transcriptionally induced by glucocorticoids and serum. AB - A novel member of the serine/threonine protein kinase gene family, designated sgk, for serum and glucocorticoid-regulated kinase, was identified in a differential screen for glucocorticoid-inducible transcripts expressed in the Con8.hd6 rat mammary tumor cell line. sgk encodes a protein of 49 kDa which has significant sequence homology (45 to 55% identity) throughout its catalytic domain with rac protein kinase, the protein kinase C family, ribosomal protein S6 kinase, and cyclic AMP-dependent protein kinase. sgk mRNA is expressed in most adult rat tissues, with the highest levels in the thymus, ovary, and lung, as well as in several rodent and human cell lines. sgk mRNA was stimulated by glucocorticoids and by serum within 30 min, and both inductions were independent of de novo protein synthesis. The transcriptional regulation by glucocorticoids is a primary response, since the promoter of sgk contains a glucocorticoid response element consensus sequence 1.0 kb upstream of the start of transcription which is able to stimulate chloramphenicol acetyltransferase reporter gene activity in a dexamethasone-dependent manner. Antibodies that specifically recognize sgk-encoded protein on an immunoblot were generated. This protein was shown to increase in abundance with glucocorticoid treatment in a manner which paralleled the mRNA accumulation. This is the first report of a presumed serine/threonine protein kinase that is highly regulated at the transcriptional level by glucocorticoid hormones and suggests a novel interplay between glucocorticoid receptor signalling and a protein kinase of the second messenger family. PMID- 8455597 TI - The COT2 gene is required for glucose-dependent divalent cation transport in Saccharomyces cerevisiae. AB - Eleven cobalt-tolerant mutants were found to belong to a single complementation group, cot2. In addition to cobalt, the cot2 mutants were found to tolerate increased levels of the divalent cations Zn2+, Mn2+, and Ni2+ as well. All of the cot2 mutants exhibited a wiener-shaped cellular morphology that was exacerbated by the carbon and nitrogen source but was unaffected by metals. The rate of glucose-dependent transport of cobalt into cells was reduced in strains that carry mutations in the COT2 gene. COT2 is not essential for growth. Strains that carry a COT2 allele conferring complete loss of function are viable and exhibit phenotypes similar to those of spontaneous cot2 mutations. The sequence of the COT2 gene shows that it is identical to GRR1, which encodes a protein required for glucose repression. The glucose dependence of the transport defect implies that cot2 mutations affect the link between glucose metabolism and divalent cation active transport. PMID- 8455598 TI - Function of the ste signal transduction pathway for mating pheromones sustains MAT alpha 1 transcription in Saccharomyces cerevisiae. AB - Sterile mutants of Saccharomyces cerevisiae were isolated from alpha * cells having the a/alpha aar1-6 genotype (exhibiting alpha mating ability and weak a mating ability as a result of a defect in a1-alpha 2 repression). Among these sterile mutants, we found two ste5 mutants together with putative ste7, ste11, and ste12 mutants of the signal transduction pathway of mating pheromones. The amino acid sequence of the Ste5p protein predicted from the nucleotide sequence of a cloned STE5 DNA has a domain rich in acidic amino acids close to its C terminus, a cysteine-rich sequence, resembling part of a zinc finger structure, in its N-terminal half, and a possible target site of cyclic AMP-dependent protein kinase at its C terminus. Northern (RNA) blot analysis revealed that STE5 transcription is under a1-alpha 2-Aar1p repression. The MAT alpha 1 cistron has a single copy of the pheromone response element in its 5' upstream region, and its basal level of transcription was reduced in these ste mutant cells. However, expression of the MAT alpha 1 cistron was not enhanced appreciably by pheromone signals. One of the ste5 mutant alleles conferred a sterile phenotype to a/alpha aar1-6 cells but a mating ability to MATa cells. PMID- 8455599 TI - Pheromone-induced signal transduction in Saccharomyces cerevisiae requires the sequential function of three protein kinases. AB - Protein phosphorylation plays an important role in pheromone-induced differentiation processes of haploid yeast cells. Among the components necessary for signal transduction are the STE7 and STE11 kinases and either one of the redundant FUS3 and KSS1 kinases. FUS3 and presumably KSS1 are phosphorylated and activated during pheromone induction by a STE7-dependent mechanism. Pheromone also induces the accumulation of STE7 in a hyperphosphorylated form. This modification of STE7 requires the STE11 kinase, which is proposed to act before STE7 during signal transmission. Surprisingly, STE7 hyperphosphorylation also requires a functional FUS3 (or KSS1) kinase. Using in vitro assays for FUS3 phosphorylation, we show that pheromone activates STE7 even in the absence of FUS3 and KSS1. Therefore, STE7 activation must precede modification of FUS3 (and KSS1). These findings suggest that STE7 hyperphosphorylation is a consequence of its activation but not the determining event. PMID- 8455601 TI - U1 small nuclear ribonucleoprotein particle-protein interactions are revealed in Saccharomyces cerevisiae by in vivo competition assays. AB - Two highly conserved regions of the 586-nucleotide yeast (Saccharomyces cerevisiae) U1 small nuclear RNA (snRNA) can be mutated or deleted with little or no effect on growth rate: the universally conserved loop II (corresponding to the metazoan A loop) and the yeast core region (X. Liao, L. Kretzner, B. Seraphin, and M. Rosbash, Genes Dev. 4:1766-1774, 1990). To examine the contribution of these regions to U1 small nuclear ribonucleoprotein particle (snRNP) activity, a competitor U1 gene, encoding a nonfunctional U1 snRNA molecule, was introduced into a number of strains carrying a U1 snRNA gene with loop II or yeast core mutations. The presence of the nonfunctional U1 gene lowered the growth rate of these mutant strains but not wild-type strains, consistent with the notion that mutant U1 RNAs are less active than wild-type U1 snRNAs. A detailed analysis of the U1 snRNA levels and half-lives in a number of merodiploid strains suggests that these mutant U1 snRNAs interact with U1 snRNP proteins less well than do their wild-type counterparts. Competition for protein factors during snRNP assembly could account for a number of previous observations in both yeast and mammalian cells. PMID- 8455600 TI - Differential function and expression of Saccharomyces cerevisiae B-type cyclins in mitosis and meiosis. AB - We have studied the patterns of expression of four B-type cyclins (Clbs), Clb1, Clb2, Clb3, and Clb4, and their ability to activate p34cdc28 during the mitotic and meiotic cell cycles of Saccharomyces cerevisiae. During the mitotic cell cycle, Clb3 and Clb4 were expressed and induced a kinase activity in association with p34cdc28 from early S phase up to mitosis. On the other hand, Clb1 and Clb2 were expressed and activated p34cdc28 later in the mitotic cell cycle, starting in late S phase and continuing up to mitosis. The pattern of expression of Clb3 and Clb4 suggests a possible role in the regulation of DNA replication as well as mitosis. Clb1 and Clb2, whose pattern of expression is similar to that of other known Clbs, are likely to have a role predominantly in the regulation of M phase. During the meiotic cell cycle, Clb1, Clb3, and Clb4 were expressed and induced a p34cdc28-associated kinase activity just before the first meiotic division. The fact that Clb3 and Clb4 were not synthesized earlier, in S phase, suggests that these cyclins, which probably have a role in S phase during the mitotic cell cycle, are not implicated in premeiotic S phase. Clb2, the primary mitotic cyclin in S. cerevisiae, was not detectable during meiosis. Sporulation experiments on strains deleted for one, two, or three Clbs indicate, in agreement with the biochemical data, that Clb1 is the primary cyclin for the regulation of meiosis, while Clb2 is not involved at all. PMID- 8455602 TI - Location of crossovers during gene targeting with insertion and replacement vectors. AB - Gene targeting was used to introduce nonselectable genetic changes into chromosomal loci in mouse embryo-derived stem cells. The nonselectable markers were linked to a selectable marker in both insertion- and replacement-type vectors, and the transfer of the two elements to the Hprt locus was assayed. When insertion vectors were used as substrates, the frequency of transfer was highly dependent upon the distance between the nonselectable marker and the double strand break in the vector. A marker located close to the vector ends was frequently lost, suggesting that a double-strand gap repair activity is involved in vector integration. When replacement vectors were used, cotransfer of a selectable marker and a nonselectable marker 3 kb apart was over 50%, suggesting that recombination between vector and target often occurs near the ends of the vector. To illustrate the use of replacement vectors to transfer specific mutations to the genome, we describe targeting of the delta F508 mutation to the CFTR gene in mouse embryo-derived stem cells. PMID- 8455603 TI - GSP1 and GSP2, genetic suppressors of the prp20-1 mutant in Saccharomyces cerevisiae: GTP-binding proteins involved in the maintenance of nuclear organization. AB - The temperature-sensitive mutation prp20-1 of Saccharomyces cerevisiae exhibits a pleiotropic phenotype associated with a general failure to maintain a proper organization of the nucleus. Its mammalian homolog, RCC1, is not only reported to be involved in the negative control of chromosome condensation but is also believed to assist in the coupling of DNA replication to the entry into mitosis. Recent studies on Xenopus RCC1 have strongly suggested a further role for this protein in the formation or maintenance of the DNA replication machinery. To elucidate the nature of the various components required for this PRP20 control pathway in S. cerevisiae, we undertook a search for multicopy suppressors of a prp20 thermosensitive mutant. Two genes, GSP1 and GSP2, were identified that encode almost identical polypeptides of 219 and 220 amino acids. Sequence analyses of these proteins show them to contain the ras consensus domains involved in GTP binding and metabolism. The levels of the GSP1 transcript are about 10-fold those of GSP2. As for S. cerevisiae RAS2, GSP2 expression exhibits carbon source dependency, while GSP1 expression does not. GSP1 is an essential gene, and GSP2 is not required for cell viability. We show that GSP1p is nuclear, that it can bind GTP in an in vitro assay, and finally, that a mutation in GSP1p which activates small ras-like proteins by increasing the stability of the GTP bound form causes a dominant lethal phenotype. We believe that these two gene products may serve in regulating the activities of the multicomponent PRP20 complex. PMID- 8455604 TI - Protein binding to a single termination-associated sequence in the mitochondrial DNA D-loop region. AB - A methylation protection assay was used in a novel manner to demonstrate a specific bovine protein-mitochondrial DNA (mtDNA) interaction within the organelle (in organello). The protected domain, located near the D-loop 3' end, encompasses a conserved termination-associated sequence (TAS) element which is thought to be involved in the regulation of mtDNA synthesis. In vitro footprinting studies using a bovine mitochondrial extract and a series of deleted mtDNA templates identified a approximately 48-kDa protein which binds specifically to a single TAS element also protected within the mitochondrion. Because other TAS-like elements located in close proximity to the protected region did not footprint, protein binding appears to be highly sequence specific. The in organello and in vitro data, together, provide evidence that D-loop formation is likely to be mediated, at least in part, through a trans-acting factor binding to a conserved sequence element located 58 bp upstream of the D loop 3' end. PMID- 8455605 TI - Bipartite structure of an early meiotic upstream activation sequence from Saccharomyces cerevisiae. AB - Diploid a/alpha Saccharomyces cerevisiae cells cease mitotic growth and enter meiosis in response to starvation. Expression of meiotic genes depends on the IME1 gene product, which accumulates only in meiotic cells. We report here an analysis of the regulatory region of IME2, an IME1-dependent meiotic gene. Deletion and substitution studies identified a 48-bp IME1-dependent upstream activation sequence (UAS). Activity of the UAS also requires the RIM11, RIM15, and RIM16 gene products, which are required for expression of the chromosomal IME2 promoter and for meiosis. Through a selection for suppressors that permit UAS activity in an ime1 deletion mutant, we identified recessive mutations in three genes, SIN3 (also called RPD1, UME4, and SDI1), RPD3, and UME6 (also called CAR80), that were previously known as negative regulators of other early meiotic genes. Mutational analysis of the IME2 UAS reveals two critical sequence elements: a G+C-rich sequence (called URS1), previously identified at many meiotic genes, and a newly described element, the T4C site, that we found at a subset of meiotic genes. In agreement with prior studies, URS1 mutations lead to elevated IME2 UAS activity in the absence of IME1. However, the URS1 mutations prevent any further stimulation of UAS activity by IME1. Repression through URS1 has been shown to require the UME6 gene product. We find that activation of the IME2 UAS by IME1 also requires the UME6 gene product. Thus, UME6 and the URS1 site both have dual negative and positive roles at the IME2 UAS. We propose that IME1 modifies UME6 to convert it from a negulator to a positive Regulor. PMID- 8455606 TI - Two cis-DNA elements involved in myeloid-cell-specific expression and gamma interferon (IFN-gamma) activation of the human high-affinity Fc gamma receptor gene: a novel IFN regulatory mechanism. AB - The human high-affinity receptor for the constant region of immunoglobulin G (human Fc gamma R1) is encoded by two mRNAs induced selectively by gamma interferon (IFN-gamma) and expressed in cells of myeloid lineage. The cis-DNA element (GRR) previously found to confer IFN-gamma responsiveness to this gene acts as an inducible enhancer and is the target of an IFN-gamma-activated factor(s) (GIRE-BP) in cells of different origins. Although the GRR motif is not related to the DNA elements involved in the regulation of other IFN-stimulated genes, GIRE-BP binding depends on the IFN-gamma-dependent activation of the 91 kDa protein known to be one of the factors of a transcriptional complex activated by IFN-alpha. Deletions of the Fc gamma R1 promoter allowed us to identify a 25 bp element, downstream from the GRR motif, conferring cell-type-specific expression. This element, called MATE (myeloid activating transcription element), is the DNA target for constitutive factors forming two complexes, MATE-BP1 and MATE-BP2. In accordance with the functional analysis, MATE-BP binding activities were detected in extracts prepared from myeloid cell lines such as THP-1, HL-60, and U-937 but not in HeLa cell extracts. The MATE motif is present not only in the promoter of other Fc receptor genes but also in several promoters of genes whose expression is restricted to monocytic cells. Our results suggest that human Fc gamma R1 gene expression in myeloid cells is initiated by the interaction of IFN-gamma-activated factors with cell-type-specific factors through their binding to the GRR and MATE motifs. PMID- 8455607 TI - Relatedness of an RNA-binding motif in human immunodeficiency virus type 1 TAR RNA-binding protein TRBP to human P1/dsI kinase and Drosophila staufen. AB - TRBP is a human cellular protein that binds the human immunodeficiency virus type 1 TAR RNA. Here, we show that the intact presence of amino acids 247 to 267 in TRBP correlates with its ability to bind RNA. This region contains a lysine- and arginine-rich motif, KKLAKRNAAAKMLLRVHTVPLDAR. A 24-amino-acid synthetic peptide (TR1) of this sequence bound TAR RNA with affinities similar to that of the entire TRBP, thus suggesting that this short motif contains a sufficient RNA binding activity. Using RNA probe-shift analysis, we determined that TR1 does not bind all double-stranded RNAs but prefers TAR and other double-stranded RNAs with G+C-rich characteristics. Immunoprecipitation of TRBP from human immunodeficiency virus type 1-infected T lymphocytes recovered TAR RNA. This is consistent with a TRBP-TAR ribonucleoprotein during viral infection. Computer alignment revealed that TR1 is highly homologous to the RNA-binding domain of human P1/dsI protein kinase and two regions within Drosophila Staufen. We suggest that these proteins are related by virtue of sharing a common RNA-binding moiety. PMID- 8455608 TI - Mouse GATA-4: a retinoic acid-inducible GATA-binding transcription factor expressed in endodermally derived tissues and heart. AB - We report the cDNA cloning and characterization of mouse GATA-4, a new member of the family of zinc finger transcription factors that bind a core GATA motif. GATA 4 cDNA was identified by screening a 6.5-day mouse embryo library with oligonucleotide probes corresponding to a highly conserved region of the finger domains. Like other proteins of the family, GATA-4 is approximately 50 kDa in size and contains two zinc finger domains of the form C-X-N-C-(X17)-C-N-X-C. Cotransfection assays in heterologous cells demonstrate that GATA-4 trans activates reporter constructs containing GATA promoter elements. Northern (RNA) analysis and in situ hybridization show that GATA-4 mRNA is expressed in the heart, intestinal epithelium, primitive endoderm, and gonads. Retinoic acid induced differentiation of mouse F9 cells into visceral or parietal endoderm is accompanied by increased expression of GATA-4 mRNA and protein. In vitro differentiation of embryonic stem cells into embryoid bodies is also associated with increased GATA-4 expression. We conclude that GATA-4 is a tissue-specific, retinoic acid-inducible, and developmentally regulated transcription factor. On the basis of its tissue distribution, we speculate that GATA-4 plays a role in gene expression in the heart, intestinal epithelium, primitive endoderm, and gonads. PMID- 8455609 TI - 3'end maturation of the Chlamydomonas reinhardtii chloroplast atpB mRNA is a two step process. AB - Inverted repeat (IR) sequences are found at the 3' ends of most chloroplast protein coding regions, and we have previously shown that the 3'IR is important for accumulation of atpB mRNA in Chlamydomonas reinhardtii (D. B. Stern, E.R. Radwanski, and K. L. Kindle, Plant Cell 3:285-297, 1991). In vitro studies indicate that 3' IRs are inefficient transcription termination signals in higher plants and have furthermore defined processing activities that act on the 3' ends of chloroplast transcripts, suggesting that most chloroplast mRNAs are processed at their 3' ends in vivo. To investigate the mechanism of 3' end processing in Chlamydomonas reinhardtii chloroplasts, the maturation of atpB mRNA was examined in vitro and in vivo. In vitro, a synthetic atpB mRNA precursor is rapidly cleaved at a position 10 nucleotides downstream from the mature 3' terminus. This cleavage is followed by exonucleolytic processing to generate the mature 3' end. In vivo run-on transcription experiments indicate that a maximum of 50% of atpB transcripts are transcriptionally terminated at or near the IR, while the remainder are subject to 3' end processing. Analysis of transcripts derived from chimeric atpB genes introduced into Chlamydomonas chloroplasts by biolistic transformation suggests that in vivo processing and in vitro processing occur by similar or identical mechanisms. PMID- 8455610 TI - Two fission yeast B-type cyclins, cig2 and Cdc13, have different functions in mitosis. AB - Cyclin B interacts with Cdc2 kinase to induce cell cycle events, particularly those of mitosis. The existence of cyclin B subtypes in several species has been known for some time, leading to speculation that key events of mitosis may be carried out by distinct functional classes of Cdc2/cyclin B. We report the discovery of cig2, a third B-type cyclin gene in Schizosaccharomyces pombe. Disruption of cig2 delays the onset of mitosis, to the degree that a cig2 null allele rescues mitotic catastrophe mutants, including those that are unable to carry out the inhibitory tyrosyl phosphorylation of Cdc2 kinase. Consistent with this, a cig2 null allele exhibits synthetic lethal interactions with cdc25ts and cdc2ts mutations. Mitotic phenotypes caused by disruption of cig2 are not reversed by increased production of Cdc13, the other fission yeast B-type cyclin that functions in mitosis. Likewise, a cdc13ts mutation is not rescued by increased gene dosage of cig2+. These data indicate that Cdc13 and Cig2 interact with Cdc2 to carry out different functions in mitosis. We suggest that some cyclin B subtypes found in other species, including humans, are also likely to have distinct, nonoverlapping functions in mitosis. PMID- 8455611 TI - Transcriptional activation of human zeta 2 globin promoter by the alpha globin regulatory element (HS-40): functional role of specific nuclear factor-DNA complexes. AB - We studied the functional interaction between human embryonic zeta 2 globin promoter and the alpha globin regulatory element (HS-40) located 40 kb upstream of the zeta 2 globin gene. It was shown by transient expression assay that HS-40 behaved as an authentic enhancer for high-level zeta 2 globin promoter activity in K562 cells, an erythroid cell line of embryonic and/or fetal origin. Although sequences located between -559 and -88 of the zeta 2 globin gene were dispensable for its expression on enhancerless plasmids, they were required for the HS-40 enhancer-mediated activity of the zeta 2 globin promoter. Site-directed mutagenesis demonstrated that this HS-40 enhancer-zeta 2 globin promoter interaction is mediated by the two GATA-1 factor binding motifs located at -230 and -104, respectively. The functional domains of HS-40 were also mapped. Bal 31 deletion mapping data suggested that one GATA-1 motif, one GT motif, and two NF E2/AP1 motifs together formed the functional core of HS-40 in the erythroid specific activation of the zeta 2 globin promoter. Site-directed mutagenesis further demonstrated that the enhancer function of one of the two NF-E2/AP1 motifs of HS-40 is mediated through its binding to NF-E2 but not AP1 transcription factor. Finally, we did genomic footprinting of the HS-40 enhancer region in K562 cells, adult nucleated erythroblasts, and different nonerythroid cells. All sequence motifs within the functional core of HS-40, as mapped by transient expression analysis, appeared to bind a nuclear factor(s) in living K562 cells but not in nonerythroid cells. On the other hand, only one of the apparently nonfunctional sequence motifs was bound with factors in vivo. In comparison to K562, nucleated erythroblasts from adult human bone marrow exhibited a similar but nonidentical pattern of nuclear factor binding in vivo at the HS-40 region. These data suggest that transcriptional activation of human embryonic zeta 2 globin gene and the fetal/adult alpha globin genes is mediated by erythroid cell-specific and developmental stage-specific nuclear factor-DNA complexes which form at the enhancer (HS-40) and the globin promoters. PMID- 8455612 TI - Linear mitochondrial DNAs of yeasts: frequency of occurrence and general features. AB - In most yeast species, the mitochondrial DNA (mtDNA) has been reported to be a circular molecule. However, two cases of linear mtDNA with specific termini have previously been described. We examined the frequency of occurrence of linear forms of mtDNA among yeasts by pulsed-field gel electrophoresis. Among the 58 species from the genera Pichia and Williopsis that we examined, linear mtDNA was found with unexpectedly high frequency. Thirteen species contained a linear mtDNA, as confirmed by restriction mapping, and labeling, and electron microscopy. The mtDNAs from Pichia pijperi, Williopsis mrakii, and P. jadinii were studied in detail. In each case, the left and right terminal fragments shared homologous sequences. Between the terminal repeats, the order of mitochondrial genes was the same in all of the linear mtDNAs examined, despite a large variation of the genome size. This constancy of gene order is in contrast with the great variation of gene arrangement in circular mitochondrial genomes of yeasts. The coding sequences determined on several genes were highly homologous to those of the circular mtDNAs, suggesting that these two forms of mtDNA are not of distant origins. PMID- 8455613 TI - Linear mitochondrial DNAs of yeasts: closed-loop structure of the termini and possible linear-circular conversion mechanisms. AB - The terminal structure of the linear mitochondrial DNA (mtDNA) from three yeast species has been examined. By enzymatic digestion, alkali denaturation, and sequencing of cloned termini, it was shown that in Pichia pijperi and P. jadinii, both termini of the linear mtDNA were made of a single-stranded loop covalently joining the two strands, as in the case of vaccinia virus DNA. The left and right loop sequences were in either of two orientations, suggesting the existence of a flip-flop inversion mechanism. Contiguous to the terminal loops, inverted terminal repeats were present. The mtDNA from Williopsis mrakii seems to have an analogous structure, although terminal loops could not be directly demonstrated. Electron microscopy revealed the presence, among linear molecules, of a small number of circular DNAs, mostly of monomer length. Linear and circular models of replication are considered, and possible conversion mechanisms between linear and circular forms are discussed. A flip-flop inversion mechanism between the inverted repeat sequences within a circular intermediate may be involved in the generation of the linear form of mtDNA. PMID- 8455614 TI - Physical detection of heteroduplexes during meiotic recombination in the yeast Saccharomyces cerevisiae. AB - We describe a general physical method for detecting the heteroduplex DNA that is formed as an intermediate in meiotic recombination in the yeast Saccharomyces cerevisiae. We use this method to study the kinetic relationship between the formation of heteroduplex DNA and other meiotic events. We show that strains with the rad50, but not the rad52, mutation are defective in heteroduplex formation. We also demonstrate that, although cruciform structures can be formed in vivo as a consequence of heteroduplex formation between DNA strands that contain different palindromic insertions, small palindromic sequences in homoduplex DNA are rarely extruded into the cruciform conformation. PMID- 8455615 TI - Autoactivation of catalytic (C alpha) subunit of cyclic AMP-dependent protein kinase by phosphorylation of threonine 197. AB - We recently found, using cultured mouse cell systems, that newly synthesized catalytic (C) subunits of cyclic AMP-dependent protein kinase undergo a posttranslational modification that reduces their electrophoretic mobilities in sodium dodecyl sulfate (SDS)-polyacrylamide gels and activates them for binding to a Sepharose-conjugated inhibitor peptide. Using an Escherichia coli expression system, we now show that recombinant murine C alpha subunit undergoes a similar modification and that the modification results in a large increase in protein kinase activity. Threonine phosphorylation appears to be responsible for both the enzymatic activation and the electrophoretic mobility shift. The phosphothreonine deficient form of C subunit had reduced affinities for the ATP analogs p fluorosulfonyl-[14C]benzoyl 5'-adenosine and adenosine 5'-O-(3-thiotriphosphate) as well as for the Sepharose-conjugated inhibitor peptide; it also had markedly elevated Kms for both ATP and peptide substrates. Autophosphorylation of C subunit preparations enriched for this phosphothreonine-deficient form reproduced the changes in enzyme activity and SDS-gel mobility that occur in intact cells. A mutant form of the recombinant C subunit with Ala substituted for Thr-197 (the only C-subunit threonine residue known to be phosphorylated in mammalian cells) was similar in SDS-polyacrylamide gel electrophoresis mobility and activity to the phosphothreonine-deficient form of wild-type C subunit. In contrast to the wild-type subunit, however, the Ala-197 mutant form could not be shifted or activated by incubation with the phosphothreonine-containing wild-type form. We conclude that posttranslational autophosphorylation of Thr-197 is a critical step in intracellular expression of active C subunit. PMID- 8455616 TI - Cell-specific helix-loop-helix factor required for pituitary expression of the pro-opiomelanocortin gene. AB - Pro-opiomelanocortin (POMC)-expressing cells appear to be the first pituitary cells committed to hormone production. In this work, we have identified an element of the POMC promoter which confers cell-specific activity. This element did not exhibit any activity on its own and required at least one other element of the promoter to manifest its cell-specific activity. Fine mutagenesis of this element indicated that a CANNTG motif is responsible for activity. This E-box motif is typical of binding sites for helix-loop-helix (HLH) transcription factors; however, the POMC cell-specific E box cannot be replaced by other E boxes like the kappa E2 site of the immunoglobulin gene or a muscle-specific E box. Similar E boxes which are present in the insulin gene promoter were shown to contribute to the pancreatic specificity of the insulin promoter. However, E-box binding proteins found in nuclear extracts from POMC-expressing AtT-20 cells and from insulin-expressing cells have different electrophoretic mobilities. The AtT 20 proteins were named CUTE (for corticotroph upstream transcription element binding) proteins, and they were not found in any other cells. CUTE proteins have DNA-binding properties characteristic of HLH transcription factors. Overexpression of the dominant negative HLH protein Id or of the ubiquitous positive HLH factor rat Pan-2 decreased or augmented POMC promoter activity, respectively. These observations are consistent with the hypothesis that CUTE factors might be heterodimers. This hypothesis was further supported by antibody shift experiments and by abrogation of DNA binding in the presence of bacterially expressed Id protein. Thus, the cell-specific CUTE proteins and their binding site in the POMC promoter appear to be important determinants for cell specificity of this promoter. The requirement for HLH factors in POMC transcription also presents the possibility that these factors are involved in differentiation of pituitary cells, in analogy with the role of HLH factors in muscle development. PMID- 8455617 TI - Degradation of ornithine decarboxylase: exposure of the C-terminal target by a polyamine-inducible inhibitory protein. AB - Polyamine-mediated degradation of vertebrate ornithine decarboxylase (ODC) is associated with the production of antizyme, a reversible tightly binding protein inhibitor of ODC activity. The interaction of antizyme with a binding element near the N terminus of ODC is essential but not sufficient for regulation of the enzyme by polyamines (X. Li and P. Coffino, Mol. Cell. Biol. 12:3556-2562, 1992). We now show that a second element present at the C terminus is required for the degradation process. Antizyme caused a conformational change in ODC, which made the C terminus of ODC more accessible. Blocking the C terminus with antibody prevented degradation. Tethering the C terminus by creating a circularly permuted, enzymatically active form of ODC prevented antizyme-mediated degradation. These data elucidate a form of feedback regulation whereby excess polyamines induce destruction of ODC, the enzyme that initiates their biosynthesis. PMID- 8455618 TI - Modulation of liver-specific transcription by interactions between hepatocyte nuclear factor 3 and nuclear factor 1 binding DNA in close apposition. AB - The liver-specific enhancer of the serum albumin gene contains an essential segment, designated eH, which binds the hepatocyte nuclear factor 3 alpha (HNF3 alpha) and ubiquitous nuclear factor 1/CCAAT transcription factor (NF1/CTF) proteins in tight apposition. We previously showed that activation of transcription by the eH site was correlated with an increase in intracellular HNF3 alpha levels during the in vitro differentiation of the hepatic cell line H2.35. We now show that transfection of an HNF3 alpha cDNA expression vector into dedifferentiated H2.35 cells is sufficient to induce transcription from the eH site. Mutational analysis of the enhancer demonstrates that NF1/CTF cooperates with HNF3 alpha to induce enhancer activity. However, when the eH site is removed from the context of the enhancer, NF1/CTF can inhibit transcriptional activation by HNF3 alpha. We conclude that the ternary complex of HNF3 alpha, NF1/CTF, and the eH site forms a novel, composite regulatory element that is sensitive to the local DNA sequence environment and suggest that the transcriptional stimulatory activity of NF1/CTF depends on its higher-order interactions with other proteins during hepatocyte differentiation. PMID- 8455619 TI - Plasma membrane-targeted ras GTPase-activating protein is a potent suppressor of p21ras function. AB - Although p21ras is localized to the plasma membrane, proteins it interacts with, such as the GTPase-activating proteins (GAPs) ras GAP and neurofibromin (NF1), are not, suggesting that one function of p21ras GTP may be to target such proteins to the plasma membrane. To investigate the effects of targeting ras GAP to the plasma membrane, ras C-terminal motifs sufficient for plasma membrane localization of p21ras were cloned onto the C terminus of ras GAP. Plasma membrane-targeted ras GAP is growth inhibitory to NIH 3T3 fibroblasts and COS cells. This growth inhibition correlates with GAP catalytic activity, since the plasma membrane-targeted C-terminal catalytic domain or the GAP-related domain of neurofibromin is inhibitory, whereas the similarly targeted N-terminal domain is not. Moreover, the inhibition is abrogated by the inactivating mutation L902I, which abolishes ras GAP catalytic activity. Coexpression of oncogenic mutant ras rescues cell viability, but the majority of rescued colonies are phenotypically untransformed. Furthermore, in focus assays, targeted ras GAP suppresses transformation by oncogenic mutant ras, and in reversion assays, targeted ras GAP can revert cells transformed by oncogenic mutant ras. Neither the targeted or nontargeted N-terminal domain nor the L902I mutant of ras GAP has any transforming activity. These data demonstrate that ras GAP can function as a negative regulator of ras and that plasma membrane localization potentiates this activity. However, if ras GAP is involved in the effector functions of p21ras, it can only be part of the effector complex for cell transformation. PMID- 8455620 TI - Myc-mediated apoptosis is blocked by ectopic expression of Bcl-2. AB - The product of the c-myc proto-oncogene is an important positive regulator of cell growth and proliferation. Recently, c-Myc has also been demonstrated to be a potent inducer of apoptosis when expressed in the absence of serum or growth factors. To further examine Myc-induced apoptosis, we coexpressed the proto oncogene bcl2, which has been shown to block apoptosis in other systems, with c myc in serum-deprived Rat 1a fibroblasts. Here we report that ectopic expression of bcl2 specifically blocks apoptosis induced by constitutive c-myc expression. Constitutive c-myc expression in serum-deprived Rat 1a cells caused a > 15-fold increase in the number of dead cells, accompanied by DNA fragmentation. However, coexpression of bcl2 with c-myc in these cells led to a 10-fold increase in the number of live cells and a significant decrease in DNA fragmentation. Thus, Bcl-2 effectively inhibits Myc-induced apoptosis in serum-deprived Rat 1a fibroblasts without blocking entry into the cell cycle. These results imply that apoptosis serves as a protective mechanism to prevent tumorigenicity elicited by deregulated Myc expression. This protective mechanism is abrogated, however, by Bcl-2 and therefore may explain the synergism between Myc and Bcl-2 observed in certain tumor cells. PMID- 8455621 TI - Structural alterations of the nucleolus in mutants of Saccharomyces cerevisiae defective in RNA polymerase I. AB - We have previously constructed mutants of Saccharomyces cerevisiae in which the gene for the second-largest subunit of RNA polymerase I (Pol I) is deleted. In these mutants, rRNA is synthesized by RNA polymerase II from a hybrid gene consisting of the 35S rRNA coding region fused to the GAL7 promoter on a plasmid. These strains thus grow in galactose but not glucose media. By immunofluorescence microscopy using antibodies against the known nucleolar proteins SSB1 and fibrillarin, we found that the intact crescent-shaped nucleolar structure is absent in these mutants; instead, several granules (called mininucleolar bodies [MNBs]) that stained with these antibodies were seen in the nucleus. Conversion of the intact nucleolar structure to MNBs was also observed in Pol I temperature sensitive mutants at nonpermissive temperatures. These MNBs may structurally resemble prenucleolar bodies observed in higher eukaryotic cells and may represent a constituent of the normal nucleolus. Furthermore, cells under certain conditions that inhibit rRNA synthesis did not cause conversion of the nucleolus to MNBs. Thus, the role of Pol I in the maintenance of the intact nucleolar structure might include a role as a structural element in addition to (or instead of) a functional role to produce rRNA transcripts. Our study also shows that the intact nucleolar structure is not absolutely required for rRNA processing, ribosome assembly, or cell growth and that MNBs are possibly functional in rRNA processing in the Pol I deletion mutants. PMID- 8455622 TI - Comparative analysis of the expression and oncogenic activities of Xenopus c-, N , and L-myc homologs. AB - A polymerase chain reaction-based cloning strategy allowed for the isolation of two distinct Xenopus L-myc genes, as well as previously isolated xc- and xN-myc genes, thus demonstrating that these three well-defined members of the mammalian myc gene family are present in lower vertebrates as well. Comparison of the Xenopus and mammalian Myc families revealed a high degree of structural relatedness at the gene and protein levels; this homology was consistent with the ability of the xc-myc1 and xN-myc1 genes to function as oncogenes in primary mammalian cells. In contrast, the xL-myc1 gene was found to be incapable of transforming rat embryo fibroblast cells, and this inactivity may relate to localized but significant differences in its putative transactivation domain. Analysis of xc-, xN-, and xL-myc gene expression demonstrated that (i) all three genes were highly expressed during oogenesis and their transcripts accumulated as abundant maternal mRNAs, (ii) each gene exhibited a distinctive pattern of expression during embryogenesis and in adult tissues, and (iii) the xL-myc1 and xL-myc2 genes were coordinately expressed in the maternal and zygotic genomes. The markedly high expression of the Xenopus myc gene family in differentiated tissues, such as the central nervous system and kidney, contrasts sharply with the low levels observed in mammalian adult tissues. These differences may reflect unique functions of the Myc family proteins in processes specific to amphibians, such as tissue regeneration. PMID- 8455623 TI - Yeast snR30 is a small nucleolar RNA required for 18S rRNA synthesis. AB - Subnuclear fractionation and coprecipitation by antibodies against the nucleolar protein NOP1 demonstrate that the essential Saccharomyces cerevisiae RNA snR30 is localized to the nucleolus. By using aminomethyl trimethyl-psoralen, snR30 can be cross-linked in vivo to 35S pre-rRNA. To determine whether snR30 has a role in rRNA processing, a conditional allele was constructed by replacing the authentic SNR30 promoter with the GAL10 promoter. Repression of snR30 synthesis results in a rapid depletion of snR30 and a progressive increase in cell doubling time. rRNA processing is disrupted during the depletion of snR30; mature 18S rRNA and its 20S precursor underaccumulate, and an aberrant 23S pre-rRNA intermediate can be detected. Initial results indicate that this 23S pre-rRNA is the same as the species detected on depletion of the small nucleolar RNA-associated proteins NOP1 and GAR1 and in an snr10 mutant strain. It was found that the 3' end of 23S pre rRNA is located in the 3' region of ITS1 between cleavage sites A2 and B1 and not, as previously suggested, at the B1 site, snR30 is the fourth small nucleolar RNA shown to play a role in rRNA processing. PMID- 8455624 TI - Activation of human heat shock genes is accompanied by oligomerization, modification, and rapid translocation of heat shock transcription factor HSF1. AB - Transcriptional activity of heat shock (hsp) genes is controlled by a heat activated, group-specific transcription factor(s) recognizing arrays of inverted repeats of the element NGAAN. To date genes for two human factors, HSF1 and HSF2, have been isolated. To define their properties as well as the changes they undergo during heat stress activation, we prepared polyclonal antibodies to these factors. Using these tools, we have shown that human HeLa cells constitutively synthesize HSF1, but we were unable to detect HSF2. In unstressed cells HSF1 is present mainly in complexes with an apparent molecular mass of about 200 kDa, unable to bind to DNA. Heat treatment induces a shift in the apparent molecular mass of HSF1 to about 700 kDa, concomitant with the acquisition of DNA-binding ability. Cross-linking experiments suggest that this change in complex size may reflect the trimerization of monomeric HSF1. Human HSF1 expressed in Xenopus oocytes does not bind DNA, but derepression of DNA-binding activity, as well as oligomerization of HSF1, occurs during heat treatment at the same temperature at which hsp gene expression is induced in this organism, suggesting that a conserved Xenopus protein(s) plays a role in this regulation. Inactive HSF1 resides in the cytoplasm of human cells; on activation it rapidly translocates to a soluble nuclear fraction, and shortly thereafter it becomes associated with the nuclear pellet. On heat shock, activatable HSF1, which might already have been posttranslationally modified in the unstressed cell, undergoes further modification. These different process provide multiple points of regulation of hsp gene expression. PMID- 8455625 TI - Differential regulation of cellular activities by GTPase-activating protein and NF1. AB - The regulation of the GTPase activity of the Ras proteins is thought to be a key element of signal transduction. Ras proteins have intrinsic GTPase activity and are active in signal transduction when bound to GTP but not following hydrolysis of GTP to GDP. Three cellular Ras GTPase-activating proteins (Ras-gaps) which increase the GTPase activity of wild-type (wt) Ras but not activated Ras in vitro have been identified: type I and type II GAP and type I NF1. Mutations of wt Ras resulting in lowered intrinsic GTPase activity or loss of response to cellular Ras-gap proteins are thought to be the primary reason for the transforming properties of the Ras proteins. In vitro assays show type I and type II GAP and the GAP-related domain of type I NF1 to have similar biochemical properties with respect to activation of the wt Ras GTPase, and it appears as though both type I GAP and NF1 can modulate the GTPase function of Ras in cells. Here we report the assembling of a full-length coding clone for type I NF1 and the biological effects of microinjection of Ras and Ras-gap proteins into fibroblasts. We have found that type I GAP, type II GAP, and type I NF1 show markedly different biological activities in vivo. Coinjection of type I GAP or type I NF1, but not type II GAP, with wt Ras abolished the ability of wt Ras to induce expression from an AP-1-controlled reporter gene. We also found that serum-stimulated DNA synthesis was reduced by prior injection of cells with type I GAP but not type II GAP or type I NF1. These results suggest that type I GAP, type II GAP, and type I NF1 may have different activities in vivo and support the hypothesis that while type I forms of GAP and NF1 may act as negative regulators of wt Ras, they may do so with differential efficiencies. PMID- 8455626 TI - Convergent regulation of NF-IL6 and Oct-1 synthesis by interleukin-6 and retinoic acid signaling in embryonal carcinoma cells. AB - The nuclear signaling by the pleiotropic cytokine interleukin-6 (IL-6) has been investigated in human embryonal carcinoma cells and T cells. We show that Oct-1, a ubiquitously expressed octamer-binding protein known to be regulated posttranslationally, can also be regulated at the levels of mRNA and protein synthesis by IL-6 and by retinoic acid (RA) in human embryonal carcinoma cells. NF-IL6, an IL-6-inducible transcription factor of the C/EBP family, can confer this regulation and is itself regulated by both signals. The abundance and the molar ratios of the three forms of NF-IL6, corresponding to peptides initiated in frame from different AUGs of the same NF-IL6 mRNA species, are regulated by IL-6 and by RA. These results suggest that the two signal transduction pathways overlap in human embryonal carcinoma cells and that Oct-1 may be downstream of NF IL6 in the shared regulatory cascade. Enhanced Oct-1 synthesis correlates with one of the functions of Oct-1, i.e., stimulation of adenovirus DNA replication. This provides an example of a possible functional consequence of IL-6 and RA signaling that is mediated by NF-IL6 and Oct-1 regulation. PMID- 8455627 TI - Interaction between NF-kappa B- and serum response factor-binding elements activates an interleukin-2 receptor alpha-chain enhancer specifically in T lymphocytes. AB - We find that a short enhancer element containing the NF-kappa B binding site from the interleukin-2 receptor alpha-chain gene (IL-2R alpha) is preferentially activated in T cells. The IL-2R alpha enhancer binds NF-kappa B poorly and is only weakly activated by the NF-kappa B site alone. Serum response factor (SRF) binds to a site adjacent to the NF-kappa B site in the IL-2R enhancer, and both sites together have strong transcriptional activity specifically in T cells. Surprisingly, the levels of SRF constitutively expressed in T cells are consistently higher than in other cell types. Overexpression of SRF in B cells causes the IL-2R enhancer to function as well as it does in T cells, suggesting that the high level of SRF binding in T cells is functionally important. PMID- 8455628 TI - Cell surface anchorage and ligand-binding domains of the Saccharomyces cerevisiae cell adhesion protein alpha-agglutinin, a member of the immunoglobulin superfamily. AB - alpha-Agglutinin is a cell adhesion glycoprotein expressed on the cell wall of Saccharomyces cerevisiae alpha cells. Binding of alpha-agglutinin to its ligand a agglutinin, expressed by a cells, mediates cell-cell contact during mating. Analysis of truncations of the 650-amino-acid alpha-agglutinin structural gene AG alpha 1 delineated functional domains of alpha-agglutinin. Removal of the C terminal hydrophobic sequence allowed efficient secretion of the protein and loss of cell surface attachment. This cell surface anchorage domain was necessary for linkage to a glycosyl phosphatidylinositol anchor. A construct expressing the N terminal 350 amino acid residues retained full a-agglutinin-binding activity, localizing the binding domain to the N-terminal portion of alpha-agglutinin. A 278-residue N-terminal peptide was inactive; therefore, the binding domain includes residues between 278 and 350. The segment of alpha-agglutinin between amino acid residues 217 and 308 showed significant structural and sequence similarity to a consensus sequence for immunoglobulin superfamily variable-type domains. The similarity of the alpha-agglutinin-binding domain to mammalian cell adhesion proteins suggests that this structure is a highly conserved feature of adhesion proteins in diverse eukaryotes. PMID- 8455629 TI - hMEF2C gene encodes skeletal muscle- and brain-specific transcription factors. AB - The myocyte enhancer-binding factor 2 (MEF2) site is an essential element of many muscle-specific enhancers and promoters that binds nuclear proteins from muscle and brain. Recently, we have cloned a family of MEF2 transcription factors produced by two genes that, at the mRNA level, are broadly expressed and produce tissue-specific isoforms by posttranscriptional processes (Y.-T. Yu, R. E. Breitbart, L. B. Smoot, Y. Lee, V. Mahdavi, and B. Nadal-Ginard, Genes Dev. 6:1783-1798, 1992). Here, we report the isolation and functional characterization of cDNA clones encoding four MEF2 factors derived from a separate gene that we have named hMEF2C. In contrast to those of the previously reported genes, the transcripts of the hMEF2C gene are restricted to skeletal muscle and brain. One of the alternate exons is exclusively present in brain transcripts. The products of this gene have DNA-binding and trans-activating activities indistinguishable from those of the previously reported MEF2 factors. The hMEF2C gene is induced late during myogenic differentiation, and its expression is limited to a subset of cortical neurons. The potential targets for this transcription factor in a subset of neurons are not known at this time. The strict tissue-specific pattern of expression of hMEF2C in comparison with the more ubiquitous expression of other MEF2 genes suggests a different mode of regulation and a potentially important role of hMEF2C factors in myogenesis and neurogenesis. PMID- 8455630 TI - Addition of constitutive c-myc expression to Abelson murine leukemia virus changes the phenotype of the cells transformed by the virus from pre-B-cell lymphomas to plasmacytomas. AB - Abelson murine leukemia virus (A-MuLV), a retrovirus that expresses the v-abl oncogene, characteristically induces pre-B-cell lymphomas following in vivo infection of BALB/c mice or in vitro infection of suspensions of fetal liver or bone marrow cells. ABL-MYC, a retrovirus that expresses both v-abl and c-myc, induces solely plasmacytomas in BALB/c mice. To investigate how the addition of overexpression of c-myc to that of v-abl accomplishes this dramatic change in the phenotype of the cells transformed by these closely related retroviruses, we utilized helper-free A-MuLV (psi 2) and ABL-MYC (psi 2) in vitro to infect suspensions of cells from different lymphoid tissues and purified immature and purified mature B cells. As expected, A-MuLV(psi 2) induced only pre-B-cell lymphomas in vivo and in vitro when immature B cells were present. ABL-MYC(psi 2), on the other hand, produced only plasmacytomas, even when purified immature B lymphocytes were infected in vitro. Although the A-MuLV(psi 2)-induced pre-B-cell lymphomas express easily detectable levels of c-myc mRNA, maturation into more mature forms of B lymphocytes is blocked. The constitutively overexpressed c-myc in the ABL-MYC retrovirus abrogates this block, permits maturation of infected immature B cells, and yields transformed plasma cells. PMID- 8455631 TI - Genetic evidence for a role for MCM1 in the regulation of arginine metabolism in Saccharomyces cerevisiae. AB - ARGRI, ARGRII, and ARGRIII regulatory proteins control the expression of arginine anabolic and catabolic genes in Saccharomyces cerevisiae. We have shown that MCM1 is part of the ARGR regulatory complex, by in vitro binding experiments, at the ARGR5,6 promoter. The participation of MCM1 in the regulation of arginine metabolism is confirmed by the behavior of an mcm1-gcn4 mutant, which is affected in the repression of arginine anabolic genes. In this mcm1 mutant, synthesis of the catabolic enzymes is rather constitutive, but this derepression requires the integrity of the ARGR system and of the target sequences of these proteins in the CAR1 promoter. Our in vitro binding experiments confirm the presence of MCM1 in the protein complex interacting with the promoters of the catabolic CAR1 and CAR2 genes. This is the first in vivo transcription role ascribed to MCM1 other than its role in the transcription of cell-type-specific genes. PMID- 8455632 TI - Contribution of sequences downstream of the TATA element to a protein-DNA complex containing the TATA-binding protein. AB - A TATA complex that forms on the hsp70 promoter has been found to depend on sequence-specific interactions that occur at the transcription start and regions further downstream. The complex was detected with a gel shift assay and further characterized with interference assays. Antibodies reveal that the TATA-binding protein is in the complex. Interference assays localize specific contacts in the TATA element, the start site, and in a region approximately 25 bp downstream of the start site that contribute to either the assembly or the maintenance of the complex. Contact at the TATA element is made in the minor groove, as has been reported for the recombinant TATA-binding protein. Mutation in the TATA element or the start site of hsp70 causes complex formation to be more strongly dependent on contacts in the +25 region than in the normal core promoter. Examination of the hsp26 and histone H4 genes indicates that similar contacts contribute to the TATA complexes that form on these promoters. The results suggest that specific contacts downstream of the TATA element could play a key role in establishing the transcriptional potential of a gene by contributing to the interaction of the TATA-binding protein. PMID- 8455633 TI - Replication-competent retroviral vectors encoding alkaline phosphatase reveal spatial restriction of viral gene expression/transduction in the chick embryo. AB - Replication-competent avian retroviruses, capable of transducing and expressing up to 2 kb of nonviral sequences, are now available to effect widespread gene transfer in chicken (chick) embryos (S. H. Hughes, J. J. Greenhouse, C. J. Petropoulos, and P. Sutrave, J. Virol. 61:3004-3012, 1987). We have constructed novel avian retroviral vectors that encode human placental alkaline phosphatase as a marker whose expression can be histochemically monitored. These vectors have been tested for expression by introducing them into the embryonic chick nervous system. They have revealed that the expression of retrovirally transduced genes can be spatially and temporally limited without the need for tissue-specific promoters. By varying the site and time of infection, targeted gene transfer can be confined to selected populations of neural cells over the course of several days, a time window that is sufficient for many key developmental processes. The capability of differentially infecting specific target populations may avoid confounding variables such as detrimental effects of a transduced gene on processes unrelated to the cells or tissue of interest. These vectors and methods thus should be useful in studies of the effect of transduced genes on the development of various organs and tissues during avian embryogenesis. In addition, the vectors will facilitate studies aimed at an understanding of viral infection and expression patterns. PMID- 8455634 TI - Structure and expression of the nuclear gene coding for the chloroplast ribosomal protein L21: developmental regulation of a housekeeping gene by alternative promoters. AB - We have cloned and sequenced the nuclear gene of the chloroplast ribosomal protein L21 (rpl21) of Spinacia oleracea. The gene consists of five exons and four introns. All introns are located in the sequence which corresponds to the Escherichia coli-like central core of the protein. L21 mRNA is present in photosynthetic (leaves) and nonphotosynthetic (roots and seeds) plant organs, although large quantitative differences exist. Primer extension and S1 nuclease mapping experiments revealed the existence of two types of transcripts in leaves. The two corresponding start sites were defined as P1 and P2. In roots and seeds, we found only the shorter of the two transcripts (initiated at P2). The nucleotide sequence surrounding P2 resembles promoters for housekeeping and vertebrate r-protein genes. Analysis of several promoter constructions by transient expression confirmed that both transcripts originate from transcription initiation. Results are interpreted to mean that the expression of the rpl21 gene is regulated by alternative promoters. One of the promoters (P2) is constitutive, and the other one (P1) is specifically induced in leaves, i.e., its activation should be related to the transformation of amyloplasts or proplastids to chloroplasts. The gene thus represents the first example of a housekeeping gene which is regulated by the organ-specific usage of alternative promoters. Primer extension analysis and S1 nuclease mapping of another nucleus-encoded chloroplast ribosomal protein gene (rps1) give evidence that the same type of regulation by two-promoter usage might be a more general phenomenon of plant chloroplast related ribosomal protein genes. Preliminary results indicate that presence of conserved sequences within the rpl21 and rps1 promoter regions which compete for the same DNA binding activities. PMID- 8455635 TI - A complex regulatory element from the yeast gene ENO2 modulates GCR1-dependent transcriptional activation. AB - The GCR1 gene product is required for maximal transcription of many yeast genes including genes encoding glycolytic enzymes. Transcription of the yeast enolase gene ENO2 is reduced 50-fold in strains carrying a gcr1 null mutation. cis-acting sequences that are sufficient for GCR1-dependent regulation of ENO2 expression were identified by using an enhancerless CYC1 promoter which is not normally dependent on GCR1 for expression. A 60-bp ENO2 sequence that was sufficient to provide high-level, GCR1-dependent transcriptional activation of the CYC1 promoter was identified. This 60-bp element could be subdivided into a 30-bp sequence containing a novel RAP1-binding site and a GCR1-binding site which did not activate CYC1 transcription and a 30-bp sequence containing a novel enhancer element that conferred moderate levels of GCR1-independent transcriptional activation. The 60-bp CGCR1-dependent upstream activator sequence is located immediately downstream from previously mapped overlapping binding sites for the regulatory proteins ABFI and RAP1. Evidence is presented that the overlapping ABFI- and RAP1-binding sites function together with sequences that bind GCR1 and RAP1 to stage transcriptional activation of ENO2 expression. PMID- 8455636 TI - Conformational dependency of human IgG heavy chain-associated Gm allotypes. AB - Human IgG allotypic markers Gm(a)[Glm(1)], Gm(x)[Glm(2)]; Gm(f)[Glm(4)], Gm(b)[G3m(5) and (11)] and Gm(g)[G3m(21)] were studied after chemical modification of IgG histidines by diethylpyrocarbonate, tyrosines by N acetylimidazole and lysines by formaldehyde and sodium borohydride. Degrees of substitution were estimated by trinitrobenzenesulfonic acid assay. IgG of known Gm phenotype isolated from serum of hyperimmune anti-tetanus toxoid donors was studied. Histidyl modification resulted in virtually complete loss of Gm(a) and Gm(g) antigenicity but preservation of Gm(x), Gm(b) and Gm(f). Reconstitution of the histidyl residues using hydroxylamine resulted in virtually complete restoration of Gm(a) and Gm(g) antigenicity. Histidine modification resulted in no significant decrease in ELISA anti-tetanus antibody activity. Alteration of tyrosyl residues using N-acetylimidazole considerably diminished Gm(a) and Gm(f) expression. This effect was reversed by hydroxylamine treatment. Moreover, chemical alteration of tyrosyl residues produced a complete loss of Gm(g) antigenicity which was only partially restored after deacylation. A urinary H chain fragment containing the VH region directly linked to C gamma 3 which contained the Gm(a) specific and Gm(x) specific amino acid residues was positive for Gm(a) but negative for Gm(x). Another urinary H chain fragment containing only the C gamma 3 domain was negative for both Gm(a) and (x). These findings indicate that Gm allotypic markers may depend on conformational determinants in which strongest expression for Gm(a) and (x) depends on structures expressed by C gamma 3 linked to C gamma 2 domains. Although RFs react with the region encompassing the C gamma 2-C gamma 3 interface, Gm-specificities of such reactions are affected allosterically through single or double amino acid substitutions at a relatively distant site. PMID- 8455637 TI - Characterization of an anti-digoxin antibody binding site by site-directed in vitro mutagenesis. AB - In vitro mutagenesis and immunoglobulin gene transfection were used to investigate the binding site of a monoclonal antibody, 2610, that binds to digoxin, a cardiac glycoside. A computer model was generated in order to select sites in the complementarity determining regions (CDR) that would participate in binding. Residues in the CDR segments were chosen that possess high solvent exposure and were located in a putative cleft. The cloned heavy and light chain variable regions were subjected to in vitro mutagenesis at these sites. The mutated variable regions in M13 were then subcloned into expression vectors and transfected. The affinities and specificity binding properties of the resultant expressed antibodies were measured. Many of the mutants of the putative contact residues showed significant but not major alterations of binding properties. Since most of the residues in the binding site are non-polar and aromatic and since many of the mutations resulted in only modest binding changes, we theorize that much of the high affinity binding (> 10(9)/M) is the cumulation of many weak interactions, arising from dispersion forces and hydrophobic effects in the pocket. Preliminary mutagenesis of two L chain positions proposed to bind to the lactone end of digoxin have larger binding effects. Specificity studies show that the mutants more frequently possess altered binding to the lactone ring of digoxin that altered binding to other digoxin moieties. The data are most suggestive of a model in which lactone is at the bottom of a binding pocket, followed by the steroid nucleus and then by the sugar moiety extruding out of the pocket. The binding information may be useful in understanding the immune response to large, hydrophobic haptens. PMID- 8455638 TI - Insertion of constant region domains of human IgG1 into CD4-PE40 increases its plasma half-life. AB - CD4-PE40 is a recombinant toxin containing the binding domain of CD4 and a mutant form of Pseudomonas exotoxin A from which the cell binding domain has been removed. To increase the serum half-life of CD4-PE40, we have inserted various portions of the constant domain of human IgG1 into CD4-PE40. The constructs made include CD4-CH2-PE40, CD4-CH3-PE40, CD4-CH1-CH2-PE40 and CD4-CH2-CH3-PE40. The fusion proteins were expressed and purified from E. coli. Insertion of various domains from the constant region of IgG1 did not alter the cytotoxic activity of CD4-PE40; all these molecules were equally cytotoxic to cells expressing gp120 on their surface. However, there was a marked increase in the serum mean residence time of CD4-CH2-PE40 which was 115 min as compared to 47 min for CD4-PE40. Insertion of other domains also increased the half-life of CD4-PE40, however, CD4 CH2-PE40 was found to have the longest mean residence time in the circulation. One possible explanation for the increase in plasma half-life is diminished susceptibility of proteins to proteolysis. It was found that CD4-CH2-PE40 was much more resistant to proteolysis by trypsin than CD4-PE40. We proposed that insertion of the CH2 domain into CD4-PE40 covers up the protease sensitive sites in the molecule, thereby making the molecule less susceptible to degradation. The increase in size and reduced sensitivity to proteases could both be responsible for the increased plasma half-life of CD4-CH2-PE40. PMID- 8455639 TI - Interferon-gamma induces polymeric immunoglobulin receptor mRNA in human intestinal epithelial cells by a protein synthesis dependent mechanism. AB - Transport of secretory IgA into external fluids is mediated by the polymeric immunoglobulin receptor (pIgR) on the surface of mucosal epithelial cells. We studied the mechanism by which interferon-gamma (IFN-gamma) induces pIgR expression in HT-29.74 cells, a subclone of the HT-29 cell line selected for high concns of pIgR. Here we report the isolation of genomic DNA and cDNA clones encoding human pIgR and development of a sensitive ribonuclease protection assay for pIgR mRNA. This assay was used to determine if induction of pIgR by IFN-gamma is mediated by accumulation of pIgR mRNA. After an initial lag of 12 hr, pIgR mRNA increased seven-fold in response to IFN-gamma, reaching a plateau at 24 hr. Concentrations of pIgR protein also increased seven-fold, but the increase was delayed until 48 hr following stimulation with IFN-gamma. Cycloheximide treatment abolished the IFN-gamma induced increase in pIgR mRNA, indicating that induction of pIgR mRNA by IFN-gamma requires de novo protein synthesis. These results suggest that induction of pIgR expression by IFN-gamma involves an increase in steady-state concns of pIgR mRNA via a protein synthesis dependent mechanism. PMID- 8455640 TI - Rapid identification of Renibacterium salmoninarum using an oligonucleotide probe complementary to 16S rRNA. AB - Bacterial kidney disease in salmonid fish is caused by the slow-growing Gram positive rod, Renibacterium salmoninarum. The partial sequence of 16S rRNA from R. salmoninarum was determined and compared with published bacterial 16S rRNA sequences. From this sequence information, a 30-bases-long oligonucleotide was designed and used as a specific probe for identification of R. salmoninarum in filter hybridization experiments. Strong specific hybridization signals were observed for all strains of R. salmoninarum tested. Furthermore, no cross hybridization could be seen against 22 other bacterial species, among them other salmonid fish pathogens. The detection limit for the probe in direct filter hybridization by the dot-blot technique was 2.5 x 10(4) bacteria. It was also possible to detect R. salmoninarum in clinical samples by direct filter hybridization. PMID- 8455641 TI - Ligation amplification and fluorescence detection of Mycobacterium tuberculosis DNA. AB - Current methods for the identification of Mycobacterium tuberculosis are dependent upon culture of the bacteria and are necessarily lengthy due to the slow growth of this agent. The development of DNA probe technology offers rapid, accurate and cost effective alternatives for the identification of such fastidious organisms. A technique for detecting specific DNA sequences, known as oligonucleotide ligation assay (OLA) involves the ligation of two adjacent oligonucleotides annealed to target DNA, and has been previously described. Amplification of the target sequences can be accomplished by including complementary pairs of oligonucleotides and a thermal stable ligase in a reaction which cycles between annealing/ligation and denaturing temperatures. Using a cloned portion of an insertion sequence, IS6110, which has been reported to be specific for M. tuberculosis complex as target DNA, we demonstrate the ligation dependent amplification of a 40 base pair region of plasmid bearing IS6110. By employing oligonucleotides which are each labelled with a different fluorescent dye, the reaction can be followed by fluorescence detection on an Applied Biosystems model 373A DNA sequencer. Using this approach, we have optimized conditions for the detection of 100 target molecules in a mixture containing 4 micrograms of unrelated DNA. Since the insertion sequence is repeated on average 12-14 times in the genome of M. tuberculosis, this corresponds to a theoretical detection level of 7-8 organisms. Completion of this entire assay can be accomplished in less than 8 h and serves as a basis for further studies in the development of a rapid clinical diagnostic test for tuberculosis. PMID- 8455642 TI - A simple colorimetric assay for detection of amplified Mycobacterium leprae DNA. AB - A colorimetric assay for the detection of PCR-products is described. The assay is based on amplification of DNA in the presence of digoxigenin-dUTP. After immobilization of the PCR products to a microtitre plate, amplified DNA could be detected colorimetrically. The sensitivity of this colorimetric assay was equal to gel-analysis allowing the detection of 100 fg of template DNA. Here, we show that it can be used to detect Mycobacterium leprae DNA in biopsy specimens from leprosy patients. The simplicity and the low degree of variation make this assay an alternative to gel-analysis. PMID- 8455643 TI - Direct sequencing of lambda DNA from crude lysates using an improved linear amplification technique. AB - We describe an improved method for directly sequencing lambda (lambda) DNA that has been isolated from either crude cleared lysates or plate lysates. This protocol does not require that the DNA be obtained from bacteriophage particles that have been purified by caesium chloride centrifugation. Nanogram quantities of lambda DNA are unidirectionally amplified using a radioactively-labelled oligonucleotide primer, and Thermus aquaticus (Taq) DNA polymerase, in the presence of T4 gene 32 protein (gp 32). The amplification/sequencing reactions are then incubated with terminal deoxynucleotidyl transferase (TdT) and all four deoxynucleotide triphosphates to elongate any prematurely-arrested products. This procedure, which is a modification of a previously-published method, results in a significant improvement in the quality and amount of DNA sequence information that can be obtained from lambda templates. Although it was developed to sequence DNA directly from lambda EMBL3 recombinants, it can also be used with cosmid DNA, M13 and plasmid DNA, and polymerase chain reaction (PCR) amplification products, yielding excellent ladders in each case. In addition, our method resolves the nucleotide sequences of double-stranded plasmid templates that are difficult to determine by conventional dideoxynucleotide sequencing protocols because of 'stalling', in which bands appear at the same position in all four lanes. PMID- 8455644 TI - Amplification of rDNA loci to detect and type Neisseria meningitidis and other eubacteria. AB - In 1991-92, Neisseria meningitidis group C was isolated from the blood of eight students in Urbana, Illinois, USA, and from the cerebrospinal fluid of one student from a nearby community, Decatur, Illinois. These and other bacterial species were analysed by PCR fingerprinting using primers selected from the ribosomal (r)DNA loci. A rDNA primer pair spanning a region within the 16S rDNA amplified a predicted 280 base pair (bp) DNA fragment from Neisseria spp. and fragments of different sizes for other genera. This primer pair specifically detected a carrier of N. meningitidis in a small clinical battery. Identity of the fragment was confirmed by restriction endonuclease analysis. A 600 bp fragment was also amplified from the 16S-23S internal transcribed spacer (ITS) of N. meningitidis; amplification from six other genera yielded different-sized fragments. Digestion of the ITS fragment from N. meningitidis with Alu I revealed three patterns; pattern I was found only for serogroup C isolates, and it was the dominant pattern among recent isolates with the exception of the one from Decatur. The isolate from Decatur yielded pattern III which suggested a non clonal relationship to the seven isolates from Urbana. Patterns II and III were more prevalent in isolates from the 1960's and 1980's. PCR-based analysis of these loci can complement the techniques which are currently used for the detection and typing of these and other eubacteria. PMID- 8455645 TI - Isolation and ordering of bacteriophage genomic clones corresponding to two YACs from 19q13.3. AB - We describe a method for rapidly isolating overlapping bacteriophage clones corresponding to the genomic region cloned in a yeast artificial chromosome (YAC) that does not require sub-cloning or lambda DNA preparation. Purified YACs from 19q13.3 were used to screen a flow-sorted chromosome 19 library, and the resulting positive clones were characterized using inter-Alu PCR. In addition, aliquots of the lambda stocks were gridded out, and hybridized with probes known to be present in the YACs, thereby avoiding having to perform DNA preparations. The application of this technique in the identification of lambda clones which span the myotonic dystrophy (DM) locus on 19q13.3 is presented, and its general advantages are discussed. PMID- 8455646 TI - Genetic variation in the Italian population at five tandem repeat loci amplified in vitro: use in paternity testing. AB - A multilocus genotype survey of 190 to 352 chromosomes was performed in Italians. Genomic DNA of five tandem repeat loci was amplified in vitro with the polymerase chain reaction. Variable number of tandem repeat (VNTR) or short tandem repeat loci investigated were: D1S80; AP0B, located in the 3' flanking region of the apolipoprotein B gene; D17S5; F8VWF, located in intron 40 of the von Willebrand factor gene; and D6S89. The repeat motif was from 2 to 70 bp. The polymerase chain reaction product size was from 100 to 1070 bp. Relative allele frequencies exhibited bimodal or complex distributions. The number of alleles detected in the sample varied from 10 for F8VWF to 20 for D1S80. The observed heterozygote frequencies of the loci ranged from 0.75 for D17S5 and F8VWF to 0.83 for D1S80, and were in accord with expected frequencies. No mutations were detected in a total of 566 meioses for the five loci studied. The most frequent genotype for all five loci combined has a frequency of 4.1 x 10(-6). In 90 parental determination cases, D1S80, AP0B, D17S5 and F8VWF gave conclusive information in 39/45 exclusions and in 21/45 attributions. PMID- 8455647 TI - Burn injury-induced nicotinic acetylcholine receptor changes on muscle membrane. AB - Patients with thermal injury show pharmacological responses akin to those seen following denervation of motor nerve where there is an increase in the number of muscle-type acetylcholine receptors (AChR). This study in the rat, examined the effect of 20%, 30%, and 50% body surface area burn injury on gastrocnemius and diaphragm AChR number, quantitated by [125I]alpha-bungarotoxin (alpha-BGT). Pharmacodynamic responses to D-tubocurarine were evaluated in the gastrocnemius muscle. AChR from gastrocnemius muscle were significantly increased in all burn groups at 14 days after burn. After 28 days, the AChR had returned to control in the 20% and 30% burn groups, but persisted in the 50% burn group. AChR from diaphragm did not show significant changes between groups. Resistance to D tubocurarine was not seen in burn groups compared with controls. Burn trauma causes increases of AChR at sites distant from the area of injury. Diaphragm muscle may be less sensitive than gastrocnemius to mediators which upregulate AChR. PMID- 8455648 TI - The estimated numbers and relative sizes of thenar motor units as selected by multiple point stimulation in young and older adults. AB - Multiple point stimulation (MPS) is described as a method of estimating the numbers of motor units in the median innervated thenar muscles of young and older control subjects. Stimulation at multiple sites along the course of the median nerve was employed to collect a sample of the lowest threshold, all-or-nothing surface-recorded motor unit action potentials (S-MUAPs). The average, negative peak area, and peak-to-peak amplitude of the sample of S-MUAPs was determined and divided into the corresponding value for the maximal compound muscle action potential to derive the motor unit estimate (MUE). In 37 trials from 17 younger subjects (20-40 years), the mean MUE was 288 +/- 95 SD based on negative peak area and, in 33 trials from 20 older subjects, mean values were 139 +/- 68. In 23 young and older subjects, MPS was performed on at least two occasions and the MUEs were found to be highly correlated (r = 0.88). PMID- 8455649 TI - Metabolic changes in reflex sympathetic dystrophy: a 31P NMR spectroscopy study. AB - The lower leg skeletal muscles of 11 patients affected by reflex sympathetic dystrophy were investigated at rest by 31P nuclear magnetic resonance spectroscopy at a fieldstrength of 1.5 T. The results were compared with similar investigations of unaffected lower leg muscles of patients and volunteers. A significant increase was observed for the average tissue pH of the muscles of affected legs as deduced from the chemical shift of the resonance for inorganic phosphate. The average inorganic phosphate/phosphocreatine ratio of these muscles was also increased. The impairment of high energy phosphate metabolism, as deduced from the NMR data, may be caused by cellular hypoxia or diminished oxygen utilization, which would agree with previous findings that oxygen extraction is reduced in extremities affected by reflex sympathetic dystrophy. PMID- 8455650 TI - Multiple descending corticospinal volleys demonstrated by changes of the wrist flexor H-reflex to magnetic motor cortex stimulation in intact human subjects. AB - To study noninvasively multiple descending volleys on alpha motoneurons, we used a 30-50% maximum H-reflex in the wrist flexor muscle conditioned by a subthreshold magnetic stimulus of the contralateral motor cortex as a parameter of motoneuronal excitability in seven neurologically healthy subjects. The time interval of the median nerve (test) stimulus and the magnetic (conditioning) stimulus was varied. In all subjects the conditioned H-reflex significantly (P < 0.05) enhanced at conditioning-test intervals between -1 ms and +10 ms. Superimposed on the overall facilitation there were at least two short duration periods of enhanced facilitation in all but one subject. These periods were separated by 2-4 ms and suggest increased excitability at the alpha motoneuronal pool brought on by the descending volleys. We conclude that with subthreshold magnetic cortical stimuli it is possible to produce multiple descending corticospinal volleys, which probably represent descending I waves. This should be taken into account when analyzing motor evoked potentials (MEPs) in clinical studies. PMID- 8455651 TI - Innervation patterns in the cat tibialis anterior six months after self reinnervation. AB - The spatial distribution of fibers belonging to a single motor unit was analyzed in 10 motor units from the tibialis anterior of the cat 6 months after denervation and self-reinnervation of the anterior (superficial) compartment of the muscle. After self-reinnervation, the distribution patterns of the fibers in the fast motor units were significantly different than control, whereas the fiber distribution in the slow unit was similar to control. Reinnervated fast units had a significant increase in the number of adjacencies among motor unit fibers, and there were often distinct "clusters or groups" of fibers distributed within the motor unit territory. Clustering or grouping of fibers was evident within the motor unit, even though fiber type grouping was not evident within the muscle. The differences in distribution patterns between control and reinnervated units may be related to variations in the branching pattern of axons during reinnervation compared to the process that occurs during development. PMID- 8455652 TI - The influence of the reference electrode on CMAP configuration. AB - The ulnar, hypothenar compound muscle action potential often shows a double peaked configuration in the negative phase component while the median, thenar potential has a simple dome shape. To investigate the origin of these differences we evaluated the activity at the belly and tendon electrode locations by referencing those sites to an electrode on the contralateral hand. The tendon sites are not electrically inactive. The ulnar tendon electrode contributes a large amplitude potential which corresponds to the second peak of the ulnar belly tendon potential. The median tendon electrode contributes only a minimal component to the negative phase of the belly-tendon potential. The distribution of such potentials throughout the hand is evaluated and possible mechanisms for the presence of a tendon potential as well as the differences between ulnar and median sites are discussed. PMID- 8455653 TI - Skeletal muscle extract and nerve growth factor have developmentally regulated survival promoting effects on distinct populations of mammalian sensory neurons. AB - Neurotrophic factors appear to be relevant to the therapy of degenerative diseases as well as neural regeneration. In this respect, we have investigated the neurotrophic effects of skeletal muscle extract on DRG neuron survival by examining the survival and neurite outgrowth promoting activity of factor(s) present in skeletal muscle extracts (SME) on dissociated cultures of embryonic or early postnatal mouse dorsal root ganglion (DRG) sensory neurons. The numbers of surviving neurons resulting from SME addition increased continuously from embryonic day 13 (15%) to birth (55%), then decreased up to 7 days after hatching (0%). Preliminary characterization of the factor(s) present in SME suggests that the active molecule is a protein different from the known neurotrophic factors NGF, BDNF, NT3, CNTF, and bFGF, and that its neurotrophic effect is not mediated by direct interaction with the substratum. PMID- 8455654 TI - Comparison of sympathetic sudomotor and skin responses in alcoholic neuropathy. AB - We evaluated sympathetic sudomotor and parasympathetic vagal function in 30 chronic alcoholic patients and 28 control subjects by means of silicone imprints, sympathetic skin responses (SSR), and cardiorespiratory reflex tests. Mean values from alcoholic patients were significantly lower than those from control subjects for all tests. The number of secreting sweat glands (SGN) was below normal in the foot of 18 patients, and in the hand of 7 patients; 16 patients had absent SSR on the sole, and 4 on the palm. Only two patients had both test results abnormal on the hand and 10 on the foot. The SGN did not correlate with the amplitude of the SSR in the subjects studied. There was no clear correlation of abnormalities found in cardiorespiratory tests and sympathetic tests. Abnormalities in sensory nerve conduction were associated with absent SSR, but not with decreased SGN. The silicone mold technique is a more specific test to detect abnormalities in sympathetic efferent fibers, as SSR may be influenced by sensory afferent fiber involvement. PMID- 8455655 TI - Search for HIV proviral DNA and amplified sequences in the muscle biopsies of patients with HIV polymyositis. AB - We searched for the presence of human immunodeficiency virus (HIV) in fresh frozen muscle biopsy specimens from 10 patients with HIV-associated polymyositis (HIV-PM) using (a) 35S-labeled HIV-RNA transcript of the virus and in situ hybridization, and (b) polymerase chain reaction and slot-blot hybridization utilizing primers amplifying sequences from the gag and pol genes of the HIV genome. With in situ hybridization, positive signals were detected in sparse lymphoid cells surrounding the muscle fibers, but not within the muscle fibers, in up to two consecutive sections in 6 of the 10 specimens. By the polymerase chain reaction, amplified HIV-specific sequences were noted in 2 specimens, but in only 2 of 8 consecutive sections, implying infection of lymphoid cells rather than muscle fibers. Muscle cultures from six specimens failed to show integrated HIV sequences within the myotubes. We conclude that HIV sequences or transcriptional products are not present within the muscle fibers or the cultured myotubes of patients with HIV-PM. This indicates that: (a) viral replication does not take place within the muscle; (b) integration of HIV proviral genome does not occur within the myonuclei or satellite cells; and (c) HIV-PM does not seem to be due to a persistent infection of the muscle fiber by the virus. PMID- 8455656 TI - Anomalous origin of the sural nerve in a patient with tibial-common peroneal nerve anastomosis. AB - Recognition of anomalous innervation patterns may be important in dealing with peripheral nerve injuries. We describe a patient who suffered injury to the common peroneal nerve (CPN) at the knee when he laterally dislocated his knee. Intraoperative nerve conduction studies during surgical exploration revealed that nerve fibers from the tibial nerve crossed over to join the CPN immediately distal to a neuroma incontinuity. The sural nerve was also found to arise totally from the CPN. PMID- 8455657 TI - The clinical significance of type 1 fiber predominance. AB - In the course of investigating children with hypotonia, muscle biopsy of the vastus lateralis frequently demonstrates greater than 55% predominance of the aerobic type 1 fibers of "type 1 fiber predominance" (T1FP). The clinical significance of T1FP is not well known. T1FP can be associated with a variety of neurological disorders but a significant proportion has no apparent cause. We followed up 23 children with T1FP to establish whether a neurological disorder subsequently became apparent or whether a distinct clinical entity of T1FP could be identified. Sixty percent of the children were found to have a specific neurological disorder, while 40% did not and may represent a distinct clinical entity. The majority of children with the clinical entity of T1FP improved although some were left with mild motor disability. Such information is important for counseling when patients with T1FP are first assessed. PMID- 8455658 TI - Deriving reference values in electrodiagnostic medicine. AB - Traditional methods for determining nerve conduction reference values have usually involved studying a group of normal controls, and determining the mean +/ 2 standard deviations (SD) for each parameter. Recent studies suggest other factors should be taken into account. Height has a greater effect on conduction velocity than age or temperature. The common assumption that conduction values follow a normal, bell-shaped Gaussian distribution appears unwarranted. The curve for some conduction parameters is significantly skewed, making a mean +/- 2 SD definition of normality inaccurate to a clinically important degree. In developing and using reference values one should consider height, age, and temperature, and calculate the mean +/- 2 SD of the transformed data to remove the effects of skew. Reference values provide only a guide to the probability a given result came from a healthy or diseased individual; one should therefore seek multiple internally consistent abnormalities before diagnosing disease on the basis of electroneurography. PMID- 8455659 TI - Acute demyelinating peripheral neuropathy in a patient with double monoclonal gammopathy and chronic myelomonocytic leukemia. PMID- 8455660 TI - Fibrillation in mitochondrial myopathy. PMID- 8455661 TI - Severity of scoliosis in patients with Duchenne muscular dystrophy at the time of referral to an orthopedic clinic. PMID- 8455662 TI - Intravenous methocarbamol in the treatment of stiff-man syndrome. PMID- 8455663 TI - Excess release of hypoxanthine from exercising muscle in patients with Kearns Sayre syndrome. PMID- 8455664 TI - Ondansetron plus metopimazine compared with ondansetron alone in patients receiving moderately emetogenic chemotherapy. AB - BACKGROUND AND METHODS: The serotonin (5-hydroxytryptamine3) antagonists have improved the treatment of acute chemotherapy-induced nausea and vomiting, but their ability to prevent delayed nausea and vomiting seems less pronounced. The results of a preliminary open trial suggested that the addition of a selective dopamine D2 antagonist could improve the antiemetic efficacy of the serotonin antagonists. In a randomized, double-blind, crossover trial, we compared oral treatment with ondansetron (8 mg twice a day) and the dopamine D2 antagonist metopimazine (30 mg four times a day) with treatment with ondansetron alone for three days in 30 patients who had vomited during the previous cycle of chemotherapy. All the patients received moderately emetogenic chemotherapy. RESULTS: Combination treatment with ondansetron and metopimazine significantly reduced the incidence of acute (P = 0.006) and delayed (P = 0.02) nausea and acute (P = 0.02) and delayed (P = 0.006) vomiting, as compared with treatment with ondansetron alone. Patients had significantly fewer days of nausea (P = 0.03) and vomiting (P = 0.003) if they received combination therapy. Sixty-seven percent of the patients preferred ondansetron and metopimazine, and 33 percent favored ondansetron alone (P = 0.10). Adverse reactions were mild with both regimens. With the exception of constipation, which was reported more frequently with combination therapy (P = 0.03), there were no significant differences in adverse reactions. CONCLUSIONS: Ondansetron plus metopimazine is a highly effective and safe antiemetic regimen that is markedly superior to treatment with ondansetron alone in patients receiving moderately emetogenic chemotherapy. PMID- 8455665 TI - Ondansetron compared with dexamethasone and metoclopramide as antiemetics in the chemotherapy of breast cancer with cyclophosphamide, methotrexate, and fluorouracil. AB - BACKGROUND: Although ondansetron was found to be effective as an antiemetic in numerous clinical trials of highly emetogenic combination-chemotherapy regimens that included cisplatin, its role in milder emetogenic regimens has not been fully defined. To address its use with a widely used but less emetogenic regimen, we performed a double-blind, randomized clinical trial comparing ondansetron with dexamethasone and metoclopramide in patients with breast cancer receiving chemotherapy with cyclophosphamide, methotrexate, and fluorouracil. METHODS: A total of 165 women with breast cancer from 14 Canadian centers who were about to receive this chemotherapy for the first time were randomly assigned to receive either ondansetron (n = 85) or dexamethasone plus metoclopramide (n = 80), a widely used, standard antiemetic regimen. The patients recorded the incidence of nausea, emesis, and other side effects in diaries, and these data were compared in the two groups. RESULTS: The patients who received dexamethasone and metoclopramide had significantly less nausea during the first 24 hours after chemotherapy was begun. Otherwise, there were no statistically significant differences in efficacy between the regimens. The incidence of drowsiness and increased appetite was higher in the group given dexamethasone and metoclopramide. CONCLUSIONS: For women with breast cancer who are being treated with cyclophosphamide, methotrexate, and fluorouracil, the efficacy of dexamethasone and metoclopramide in controlling nausea and vomiting equaled or exceeded that of ondansetron. PMID- 8455666 TI - Comparison of cardiac pacing with drug therapy in the treatment of neurocardiogenic (vasovagal) syncope with bradycardia or asystole. AB - BACKGROUND: The efficacy of permanent cardiac pacing in patients with neurocardiogenic (or vasovagal) syncope associated with bradycardia or asystole is not clear. We compared the efficacy of cardiac pacing with that of oral drug therapy in the prevention of hypotension and syncope during head-up tilt testing. METHODS: Among 70 patients with a history of syncope in whom hypotension and syncope could be provoked during head-up tilt testing, 22 had bradycardia (a heart rate < 60 beats per minute, with a decline in the rate by at least 20 beats per minute) or asystole along with hypotension during testing. There were 9 men and 13 women, with a mean (+/- SD) age of 41 +/- 17 years. Head-up tilt testing was repeated during atrioventricular sequential pacing (in 20 patients with sinus rhythm) or ventricular pacing (in 2 patients with atrial fibrillation). Regardless of the results obtained during artificial pacing, all the patients subsequently had upright-tilt testing repeated during therapy with oral metoprolol, theophylline, or disopyramide. RESULTS: During the initial tilt test, 6 patients had asystole and 16 had bradycardia along with hypotension. Despite artificial pacing, the mean arterial pressure during head-up tilt testing still fell significantly, from 97 +/- 19 to 57 +/- 19 mm Hg (P < 0.001); 5 patients had syncope, and 15 had presyncope. By contrast, 19 patients who later received only medical therapy (metoprolol in 10, theophylline in 3, and disopyramide in 6), 2 patients who received both metoprolol and atrioventricular sequential pacing, and 1 patient who received only atrioventricular sequential pacing had negative head up tilt tests. After a median follow-up of 16 months, 18 of the 19 patients who were treated with drugs alone (94 percent) remained free of recurrent syncope or presyncope, whereas the patient treated only with permanent dual-chamber pacemaker had recurrent syncope. CONCLUSIONS: In patients with neurocardiogenic syncope associated with bradycardia or asystole, drug therapy is often effective in preventing syncope, whereas artificial pacing is not. PMID- 8455667 TI - Trends in Medicare payments in the last year of life. AB - BACKGROUND: Increased attention is being paid to the amount and types of medical services rendered in the period before death. There is a popular impression that a greater share of resources is being devoted to dying patients than in the past. We examined trends in the proportion of Medicare expenditures for persons 65 years old or older in their last year of life to determine whether there were any changes from 1976 to 1988. METHODS: Using Medicare program data for 1976, 1980, 1985, and 1988, we classified Medicare payments according to whether they were made for people in their last year of life (decedents) or for survivors. We also assigned expenses for care in the last year of life according to intervals of 30 days before the person's death and examined trends according to age. RESULTS: Reflecting the large overall increase in Medicare spending, Medicare costs for decedents rose from $3,488 per person-year in 1976 to $13,316 in 1988. However, Medicare payments for decedents as a percentage of the total Medicare budget changed little, fluctuating between 27.2 and 30.6 percent during the study period. Payments for care during the last 60 days of life expressed as a percentage of payments for the last year also held steady at about 52 percent. Furthermore, the pattern of lower payments for older as compared with younger decedents also prevailed throughout the study period. CONCLUSIONS: The same forces that have acted to increase overall Medicare expenditures have affected care for both decedents and survivors. There is no evidence that persons in the last year of life account for a larger share of Medicare expenditures than in earlier years. PMID- 8455668 TI - Open-angle glaucoma. PMID- 8455669 TI - Case records of the Massachusetts General Hospital. Weekly Clinicopathological exercises. Case 15-1993. A 58-year-old man with recurrent lower gastrointestinal bleeding for over two years. PMID- 8455670 TI - Postmenopausal hormone-replacement therapy. PMID- 8455671 TI - Neurocardiogenic syncope. PMID- 8455672 TI - Management of head injury. PMID- 8455673 TI - Management of head injury. PMID- 8455674 TI - Management of head injury. PMID- 8455675 TI - Management of head injury. PMID- 8455676 TI - Management of head injury. PMID- 8455677 TI - Lorenzo's oil and thrombocytopenia in patients with adrenoleukodystrophy. PMID- 8455678 TI - Folate deficiency to protect against malaria. PMID- 8455680 TI - Confidentiality. PMID- 8455679 TI - Folate deficiency to protect against malaria. PMID- 8455681 TI - Genetic and environmental influences on serum lipid levels in twins. AB - BACKGROUND: The extent to which serum lipid levels are affected by genetic and environmental factors remains a point of controversy. We examined both genetic and environmental influences on serum lipid levels in twins reared either together or apart who participated in the Swedish Adoption/Twin Study of Aging. METHODS: We studied 302 pairs of twins (mean age, 65.6 years; range, 52 to 86); 146 pairs had been reared apart. We simultaneously compared the twins on the basis of both zygosity and rearing status, which allowed joint estimation of genetic and environmental influences on serum lipid levels. Genetic influence was expressed in terms of heritability, the proportion of the population variation attributable to genetic variation (a value of 1.0 indicates that all of the population variation is attributable to genetic variation). The serum lipids and apolipoproteins measured included total cholesterol, high-density lipoprotein cholesterol, apolipoproteins A-I and B, and triglycerides. RESULTS: Structural equation analyses revealed substantial heritability for the serum levels of each lipid measured, ranging from 0.28 to 0.78. Comparisons of the twins reared together with those reared apart suggested that the environment of rearing had a substantial impact on the level of total cholesterol (accounting for 0.15 to 0.36 of the total variance). Sharing the same environment appeared to affect the other lipid measures much less, however, than did genetic factors and unique environmental factors not shared by twins. Comparisons of younger with older twins suggested that heritability for apolipoprotein B and triglyceride levels decreased with age. CONCLUSIONS: The effect of genetic factors on the serum levels of some but not all lipids appears to decrease with age. Early rearing environment appears to remain an important factor in relation to levels of total cholesterol later in life, but it has less effect on other serum lipids and apolipoproteins in the elderly. PMID- 8455682 TI - Improved renal function in children with cystinosis treated with cysteamine. AB - BACKGROUND: The lysosomal storage disease cystinosis results in renal failure at approximately 10 years of age. Although oral cysteamine therapy is recognized to preserve kidney function, the extent of renal benefit has not been determined. METHODS: Between 1960 and 1992, we determined 24-hour creatinine clearances in 76 children with cystinosis during 1081 admissions to the National Institutes of Health. Seventeen children were considered to have received adequate treatment with cysteamine, since they had depletion of cystine from leukocytes and began therapy before the age of 2 years; treatment lasted a mean of 7.1 years. Thirty two children were considered to have received partial treatment, since they had poor compliance with therapy or began treatment after the age of 2; treatment lasted a mean of 4.5 years. Twenty-seven children were followed in the era before cysteamine therapy and thus never received cysteamine. RESULTS: Of the 27 children who never received cysteamine, 16 were followed at the National Institutes of Health until renal failure occurred; their mean (+/- SD) creatinine clearance was 8.0 +/- 4.8 ml per minute per 1.73 m2 of body-surface area at a mean age of 8.3 +/- 1.9 years. Of the 17 children who received adequate treatment, none had renal failure; their mean creatinine clearance was 57 +/- 20 ml per minute per 1.73 m2 at 8.3 +/- 3.8 years of age. The mean creatinine clearance of the children who received partial or adequate treatment with cysteamine increased with age up to the age of five years and then declined linearly with age at a normal rate. For the children who received adequate treatment, the mean creatinine clearance was predicted to reach 0 ml per minute per 1.73 m2 at the age of 74 years, as compared with 20 years of age for the children who received partial treatment. With no therapy, the mean creatinine clearance reaches 0 ml per minute per 1.73 m2 at 10 years of age. CONCLUSIONS: Children with cystinosis who are treated early and adequately with cysteamine have renal function that increases during the first five years of life and then declines at a normal rate. Patients with poorer compliance and those who are treated at an older age do less well. PMID- 8455683 TI - Brief report: primary infection with zidovudine-resistant human immunodeficiency virus type 1. PMID- 8455684 TI - Abdominal aortic aneurysm. PMID- 8455685 TI - Seminars in medicine of the Beth Israel Hospital, Boston. Pathogenesis of diseases induced by human lymphotropic virus type I infection. PMID- 8455686 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 16-1993. A 13-year-old girl with gross hematuria four years after a diagnosis of idiopathic pulmonary hemosiderosis. PMID- 8455687 TI - A tale of two mutants. PMID- 8455688 TI - Amniotomy in labor--how helpful is it? PMID- 8455689 TI - Publication of sponsored symposiums in medical journals. PMID- 8455690 TI - Publication of sponsored symposiums in medical journals. PMID- 8455691 TI - Publication of sponsored symposiums in medical journals. PMID- 8455692 TI - Publication of sponsored symposiums in medical journals. PMID- 8455693 TI - Atrial systolic failure in cardiac amyloidosis. PMID- 8455694 TI - Atrial systolic failure in cardiac amyloidosis. PMID- 8455695 TI - Nonmelanoma cancers of the skin. PMID- 8455696 TI - Nonmelanoma cancers of the skin. PMID- 8455697 TI - Health care surrogate laws. PMID- 8455698 TI - Health care surrogate laws. PMID- 8455699 TI - Doctors' estimates of U.S. health care spending. PMID- 8455700 TI - Offering a celebrity experimental treatment. PMID- 8455701 TI - Managed competition. PMID- 8455702 TI - Geneticists win Crafoord Prize. PMID- 8455703 TI - MicroGeneSys drops out of NIH trial for AIDS vaccine. PMID- 8455704 TI - Centocor takes the bad news with the good. PMID- 8455705 TI - Swiss do well on patents but demand results. PMID- 8455706 TI - Cold Spring Harbour promotes Stillman. PMID- 8455707 TI - Biologists denounce UC role in funding start-up companies. PMID- 8455708 TI - US meat inspections may get a strong dose of science. PMID- 8455709 TI - Gene therapy. PMID- 8455710 TI - Wrong site for Japanese labs. PMID- 8455711 TI - Where the AIDS virus hides away. PMID- 8455712 TI - Developmental neurobiology. Recitative and aria. PMID- 8455713 TI - AIDS. Where has HIV been hiding? PMID- 8455714 TI - Protein engineering. Making of the minibody. PMID- 8455715 TI - Cell biology. Bridging the gap. PMID- 8455716 TI - Optimality, mutation and the evolution of ageing. AB - Evolutionary explanations of ageing fall into two classes. Organisms might have evolved the optimal life history, in which survival and fertility late in life are sacrificed for the sake of early reproduction and survival. Alternatively, the life history might be depressed below this optimal compromise by deleterious mutations: because selection against late-acting mutations is weaker, these will impose a greater load on late life. Evidence for the importance of both is emerging, and unravelling their relative importance presents experimentalists with a major challenge. PMID- 8455717 TI - SNAP receptors implicated in vesicle targeting and fusion. AB - The N-ethylmaleimide-sensitive fusion protein (NSF) and the soluble NSF attachment proteins (SNAPs) appear to be essential components of the intracellular membrane fusion apparatus. An affinity purification procedure based on the natural binding of these proteins to their targets was used to isolate SNAP receptors (SNAREs) from bovine brain. Remarkably, the four principal proteins isolated were all proteins associated with the synapse, with one type located in the synaptic vesicle and another in the plasma membrane, suggesting a simple mechanism for vesicle docking. The existence of numerous SNARE-related proteins, each apparently specific for a single kind of vesicle or target membrane, indicates that NSF and SNAPs may be universal components of a vesicle fusion apparatus common to both constitutive and regulated fusion (including neurotransmitter release), in which the SNAREs may help to ensure vesicle-to target specificity. PMID- 8455718 TI - A Lyme borreliosis cycle in seabirds and Ixodes uriae ticks. AB - The Lyme disease spirochaete, Borrelia burgdorferi s.l., is the only Borrelia known to infect both mammals and birds. The main vertebrate reservoirs of B. burgdorferi are thought to be various small and intermediate size mammals, but the importance of birds as a reservoir has not been thoroughly explored. In the Northern and Southern Hemispheres the seabird tick, Ixodes uriae, is prevalent and closely associated with many species of colony-nesting marine birds. Here we report the presence of spirochaetes, demonstrated by immunofluorescent assay, by polymerase chain reaction and in culture, in I. uriae infesting razorbills on an island in the Baltic Sea. This island is free from mammals. The protein profile of the spirochaetes and the sequences of their flagellin and ospA genes are identical to those of the Lyme disease spirochaete, Borrelia burgdorferi s.l., previously isolated from I. ricinus on a nearby island. In biopsies from the foot web of razorbills, B. burgdorferi-specific DNA was detected after amplification by polymerase chain reaction. Our results suggest that birds play an important part in the maintenance of B. burgdorferi and that mammals may not be a prerequisite for its life cycle. PMID- 8455719 TI - The neural correlates of the verbal component of working memory. AB - By repeating words 'in our head', verbal material (such as telephone numbers) can be kept in working memory almost indefinitely. This 'articulatory loop' includes a subvocal rehearsal system and a phonological store. Little is known about neural correlates of this model of verbal short-term memory. We therefore measured regional cerebral blood flow, an index of neuronal activity, in volunteers performing a task engaging both components of the articulatory loop (short-term memory for letters) and a task which engages only the subvocal rehearsal system (rhyming judgement for letters). Stimuli were presented visually and the subjects did not speak. We report here that comparisons of distribution of cerebral blood flow in these conditions localized the phonological store to the left supramarginal gyrus whereas the subvocal rehearsal system was associated with Broca's area. This is, to our knowledge, the first demonstration of the normal anatomy of the components of the 'articulatory loop'. PMID- 8455720 TI - A single amino acid of the cholecystokinin-B/gastrin receptor determines specificity for non-peptide antagonists. AB - The brain cholecystokinin-B/gastrin receptor (CCK-B/gastrin) has been implicated in mediating anxiety, panic attacks, satiety, and the perception of pain. The canine and human CCK-B/gastrin receptors share 90% amino-acid identity and have similar agonist affinities. These receptors can be selectively blocked by the non peptide benzodiazepine-based antagonists L365260 (ref. 8) and L364718 (ref. 9); however, the binding of these antagonists to the human and canine receptors differs by up to 20-fold, resulting in a reversal of affinity rank order. Here we report the identification of a single amino acid in the sixth transmembrane domain of the CCK-B/gastrin receptor that corresponds to valine 319 in the human homologue and which is critical in determining the binding affinity for these non peptide antagonists. We show that it is the variability in the aliphatic side chain of the amino acid in position 319 that confers antagonist specificity. Substitution of valine 319 with a leucine residue decreases the affinity for L365260 20-fold while concomitantly increasing the affinity for L364718. An isoleucine in the same position of the human receptor selectively increases affinity for L364718. Interspecies differences in the aliphatic amino acid occupying this single position selectively affect antagonist affinities without altering the agonist binding profile. We therefore conclude that the residues underlying non-peptide antagonist affinity must differ from those that confer agonist specificity. To our knowledge, these findings are the first example in which a critical antagonist binding determinant for a seven-transmembrane-domain peptide hormone receptor has been identified. PMID- 8455721 TI - SNAP family of NSF attachment proteins includes a brain-specific isoform. AB - The soluble NSF attachment proteins (SNAPs) enable N-ethyl-maleimide-sensitive fusion protein (NSF) to bind to target membranes. Here we report the cloning and sequencing of complementary DNAs encoding alpha-, beta- and gamma-SNAPs. Two of these proteins, alpha and gamma, are found in a wide range of tissues, and act synergistically in intra-Golgi transport. The third, beta, is a brain-specific isoform of alpha-SNAP. Thus, NSF and SNAPs appear to be general components of the intracellular membrane fusion apparatus, and their action at specific sites of fusion must be controlled by SNAP receptors particular to the membranes being fused, as described in the accompanying article. PMID- 8455722 TI - HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease. AB - Primary infection with the human immunodeficiency virus (HIV) is generally followed by a burst of viraemia with or without clinical symptoms. This in turn is followed by a prolonged period of clinical latency. During this period there is little, if any, detectable viraemia, the numbers of infected cells in the blood are very low, and it is extremely difficult to demonstrate virus expression in these cells. We have analysed viral burden and levels of virus replication simultaneously in the blood and lymphoid organs of the same individuals at various stages of HIV disease. Here we report that in early-stage disease there is a dichotomy between the levels of viral burden and virus replication in peripheral blood versus lymphoid organs. HIV disease is active in the lymphoid tissue throughout the period of clinical latency, even at times when minimal viral activity is demonstrated in blood. PMID- 8455723 TI - Mechanical basis of meiotic metaphase arrest. AB - Control of the metaphase to anaphase transition is a central component of cell cycle regulation. Arrest at either metaphase I or II before fertilization is a common component of oogenesis in many organisms. In Drosophila melanogaster females, this arrest occurs at meiosis I with the chiasmate bivalents tightly massed at the metaphase plate and the nonexchange chromosomes positioned between the plate and the poles on long tapered spindles. Meiosis resumes only after passage through the oviduct. Thus, metaphase arrest defines an important checkpoint in the meiotic cell cycle. We report here that this arrest results from the balancing of chiasmate bivalents at the metaphase plate. Two meiotic mutations, mei-9b and mei-218a4, both of which greatly reduce the frequency of chiasma formation, bypass the metaphase block and allow stage 14 oocytes to finish both meiotic divisions without arrest. We conclude that metaphase arrest results from the balancing of kinetochore forces due to chiasmata. PMID- 8455724 TI - A designed metal-binding protein with a novel fold. AB - A major challenge in protein design is to create stable scaffolds into which tailored functions can be introduced. Here we present the design, synthesis and characterization of a 61-residue all-beta protein: the minibody. We used a portion of the heavy chain variable domain of an immunoglobulin as a template, obtaining a molecule with a novel beta-sheet scaffold and two regions corresponding to the hypervariable loops H1 and H2. To exploit the potential for creating functional centres in the minibody, we engineered a metal-binding site into it. This site is formed by one histidine in H1 and two in H2. The protein is folded, compact and able to bind metal, thus representing the first designed beta protein with a novel fold and a tailored function. By randomizing the sequence of the hypervariable loops, we are using the minibody scaffold to construct a conformationally constrained peptide library displayed on phage. PMID- 8455726 TI - Ethics in the age of health care reform. AB - The health care reform movement includes four ideological models. True reform will capture and integrate elements of each model and agenda, along with an underlying respect for human dignity. PMID- 8455725 TI - An interview with Mae Taylor Moss. Interview by Connie R. Curran. AB - Mae Taylor Moss, MSN, RN, the recipient of the 1992 Nursing Economic$ Excellence Award, is assistant vice president of perioperative services, St. Luke's Episcopal Hospital, Houston, TX. In this interview, Ms. Taylor Moss discusses the challenges facing her department and her strategies for decreasing costs while increasing revenues and motivating staff. PMID- 8455727 TI - Nurse executive turnover. AB - Nurse executives may change their employment status frequently and sometimes unexpectedly. This study describes the employment patterns among nurse executives participating in the Johnson and Johnson Wharton Fellows Program. PMID- 8455728 TI - Home health care agencies: what constitutes success? AB - Dramatic changes in the health care delivery system have produced a highly competitive environment for home health agencies. This study examined the characteristics perceived to be present in successful home health agencies. The results reflect both similarities and differences from studies of successful hospitals and businesses. PMID- 8455730 TI - A new accountability in health care: providers, insurers, and patients. PMID- 8455729 TI - Restructuring nursing for a competitive health care environment. PMID- 8455732 TI - From vertical to horizontal nursing management. PMID- 8455733 TI - The technology of pain relief. PMID- 8455731 TI - Restructuring the nursing service organization. PMID- 8455734 TI - Becoming the best: a case for best practice. PMID- 8455735 TI - Practical budgeting for the operating room administrator. AB - To meet the challenge of an annual budget controlled by revenue projections and cost-containment initiatives, an OR administration reviewed all expenditures, planned new initiatives, evaluated service expansion, and created an environment to encourage new products and services while maintaining quality. This revenue enhancement project maintained the institution's market share and increased revenue. PMID- 8455736 TI - [Peracute reflex dystrophy]. PMID- 8455737 TI - [Limits to the shifting of limitations; medical approach in severely handicapped newborn infants]. PMID- 8455738 TI - [Cognitive therapy in fear and depression]. PMID- 8455739 TI - [Iron deficiency, a simple diagnosis?]. PMID- 8455740 TI - [Continuation or withdrawal of life-sustaining procedures in newborn infants: a study in 4 centers for neonatal intensive care]. AB - OBJECTIVE: To provide data about continuation or withdrawal of life sustaining therapy in the critical ill newborn. METHOD: Retrospective examination of the histories of all 185 patients who died during the year 1990 (17% of total admissions) in 4 out of the 10 neonatal intensive care units in the Netherlands. RESULTS: The mean gestational age was 31.9 weeks (range 23-43; SD 5.5) and the mean birth weight 1827 g (455-5820; SD 1105). 136 infants were prematurely born, 49 full term. Intensive care was not started in 17 (9%) of the 185 patients and intensive care was withdrawn in 58 patients (31%) because there was no chance of survival. Therapy was withdrawn because of the poor prognosis for the quality of later life in 35 patients (19%). Intensive therapy was continued until death occurred in 74 infants (40%). Respiratory and circulatory problems, infections and severe acquired neurological damage were the main causes of death (32%, 17%, 19% and 24% of the cases respectively). In the cases of death due to respiratory and circulatory failure treatment was continued as long as possible. In infants who died with neurological damage as the main diagnosis, treatment was withdrawn because of the poor prognosis for the quality of life in 25 out of 44 infants. CONCLUSION: Life sustaining therapy was withdrawn or not started in 5% of the patients admitted because there was no chance of survival and in 3% because of a poor prognosis for the quality of later life. PMID- 8455742 TI - [Congenital disorders in the first year of life]. AB - OBJECTIVE: Assessment of the prevalence of congenital malformations in a population-based birth cohort of 2151 children. METHOD: Information about congenital malformations was obtained of 2092 infants by the Child Health Clinic nurses and by the CHC physician during six consultations in the first year of life. RESULTS: In 29% of the infants a congenital malformation was diagnosed. In 37 children (1.8%) 40 major malformations were found. More than three quarters of the malformations were diagnosed in the first three months of life. Using the EUROCAT criteria, a difference existed between the incidence of congenital malformations in liveborn infants in SMOCK (4.0%) and in EUROCAT (2.3%). This difference is mainly caused by the difference in the number of reports on congenital hip dislocation. The prevalence of major defects was similar in both SMOCK (central nervous system: 14/10,000; circulatory system: 67/10,000; ventricular septal defect 29/10,000; schisis: 14/10,000; Down syndrome: 14/10,000) and EUROCAT: CONCLUSION: By systematic and structured reporting it is possible to obtain more complete information on the prevalence of congenital malformations than by voluntary notification. One quarter of the congenital malformations is not detected before the age of 3 months. PMID- 8455741 TI - [Good results of treatment of reflex sympathetic dystrophy with a 50% dimethylsulfoxide cream]. AB - In this open prospective study dimethyl sulfoxide (DMSO), a hydroxyl radical scavenger, was tested in a 50% concentration in a fatty cream base (cremor vaselini cetomacrogolis FNA) in a total of 37 patients suffering from reflex sympathetic dystrophy. Patients were selected according to an RSD screening protocol. They also received physiotherapy. Eligible patients presented with acute signs of RSD and needed to have a sensation of heat in the extremity, as well as at least two of the following symptoms: (distal) pain, redness, swelling, loss of function, hyperhidrosis or increased hair growth and/or nail growth. Endpoints were the clinical improvement of the patient together with the patient's assessment of the pain according to a Visual Analog Scale (VAS: 0-10; 0 = no pain, 10 = unbearable pain). Successful treatment was accomplished when the VAS was halved and clinical signs had improved. The results showed a significant improvement in VAS score from 5.3 (SD 2.9) to 0.9 (SD 1.3; p < 0.01) in a mean treatment time of 3.4 months (SD 1.9). Systemic side effects consisted of a sulfurous smell of the exhaled breath of 12 patients. Concerning local side effects a mild dry, scaling effect on the skin was seen. PMID- 8455743 TI - [Issue of instructions concerning informational and spatial privacy]. PMID- 8455744 TI - [Greater decrease in lung function in COPD during continuous rather than during symptom-oriented bronchodilator medication]. PMID- 8455745 TI - [A normal vaginal smear and still cervical cancer]. PMID- 8455746 TI - [A normal vaginal smear and still cervical cancer]. PMID- 8455747 TI - [Controversies in preventive health care. II. Preconceptional and prenatal care]. PMID- 8455748 TI - [Computerized tomography following arthrography in instability of the shoulder joint]. PMID- 8455749 TI - [Wrong questions, erroneous answers; an absurd choice]. PMID- 8455750 TI - Methods nurses use to identify and intervene with the patient at risk for psychiatric water intoxication. PMID- 8455751 TI - Focus on ethics: ANA issues position statements. PMID- 8455752 TI - Case management: what's it all about? PMID- 8455753 TI - My "turfdom" for a nurse. PMID- 8455754 TI - CAT is coming--CAT is coming--CAT is coming. PMID- 8455755 TI - Delegation--is it an important issue for me? PMID- 8455756 TI - Telephone advice for parents of newborns. PMID- 8455757 TI - Surgical decisions on the basis of magnetic resonance angiography of the carotid arteries. AB - The recent demonstration of the efficacy of carotid endarterectomy in certain patients emphasizes the advantages of having a noninvasive, accurate means of evaluating the carotid arteries. Advances in magnetic resonance (MR) angiography now allow accurate depiction of the carotid arteries that may be adequate for surgical planning in many cases. This report examines the accuracy of MR angiography compared with that of conventional angiography in symptomatic patients undergoing carotid endarterectomy and compares them with surgical findings. Twenty-one carotid arteries in 20 patients were treated surgically for severe stenosis or occlusion. Preoperatively, all patients had both MR and conventional angiograms, which were interpreted on a five-grade scale by two independent neuroradiologists who were unaware of the patient's clinical history. The two studies were highly correlated, particularly in the case of severe stenosis and occlusion. There were no false-negative MR studies that missed surgically significant lesions. In two cases, MR angiography overestimated the stenosis by one grade. On MR angiography, surgically significant stenosis appears as focal areas of signal intensity loss at the level of stenosis with reappearance of the signal distally. If the distal signal intensity does not reappear, the artery is likely to be occluded. In symptomatic patients, MR angiograms that demonstrate a flow-void gap with distal reappearance at a site consistent with the symptoms may be adequate as the sole preoperative study. Three patients who underwent carotid endarterectomy on this basis are presented. The factors that contribute to artifactual and overestimated stenosis are reviewed. PMID- 8455758 TI - Subsequent bleeding from ruptured intracranial aneurysms treated by wrapping or coating: a review of the long-term results in 47 cases. AB - Forty-seven patients, who underwent surgery over a 34-year period by the wrapping or coating of ruptured intracranial aneurysms, have been retrospectively evaluated. The following materials were used in the surgical procedures: muscle with gelatin sponge (7 cases), gauze (2 cases), oxidized cellulose with Biobond (28 cases), Histoacryl with gauze or fascia (10 cases). The patients were monitored for up to 37 years (mean, 13.7 +/- 8.2 yr). One or more subsequent bleedings occurred in eight patients (17%). Three patients had additional bleeding and died in the early postoperative phase (within 1 mo after surgery). In five patients, the subsequent bleeding occurred between 1 and 15 years postoperatively, with two fatalities. One patient experienced two recurrences. Therefore, the mortality rate for postoperative bleedings was 10.6% (five patients) in the whole series, and the incidence of early (within 1 mo after surgery) fatal bleedings was 6.4%. After the first month from the initial hemorrhage, the global risk of subsequent bleeding was 0.93%/yr. Among the nine patients whose aneurysms were wrapped with muscle, gelatin sponge, or gauze, four additional bleedings occurred, whereas four relapses were observed among the 38 cases treated by employing bioadhesive agents (P < 0.04; Fisher's exact test). The rate of further bleeding was higher (25%) in patients undergoing surgery in the premicrosurgical era compared with that (8.7%) recorded in patients treated by microsurgery (difference statistically not significant). PMID- 8455759 TI - Chondrosarcoma of the skull base: a series of eight cases. AB - Chondrosarcomas of the skull base are indolent, locally invasive tumors with a marked tendency to recur. Surgery is the mainstay of treatment because these tumors are generally resistant to other forms of treatment. A surgical approach with wide access to the skull base and one that is easily repeatable is required, because recurrence is common. We have used the LeFort I maxillotomy or mobilization of the zygoma at the time of craniotomy to obtain wide access to the skull base in eight cases of chondrosarcoma. Three patients have undergone subsequent procedures by us for recurrent disease. One patient died 30 days after the operation, and one has required an open repair of a cerebrospinal fluid leak. Good palliation of symptoms has been achieved in all survivors. These approaches fulfill the criteria for the surgical management of these difficult tumors by allowing excellent exposure, safe repetition if required, satisfactory palliation, and acceptable morbidity. PMID- 8455760 TI - The treatment of anaplastic oligodendrogliomas and mixed gliomas. AB - We evaluated the treatment outcome of 17 patients with anaplastic oligodendroglioma and 17 patients with anaplastic mixed oligodendroglioma astrocytoma. In the anaplastic oligodendroglioma group, eight patients were treated at the time of the initial admission with radiotherapy and adjuvant chemotherapy, and nine patients were treated at the time of recurrence with salvage chemotherapy. Three patients for whom adjuvant chemotherapy was not successful were also treated with chemotherapy at the time of recurrence. In the initial group, one patient had complete response, three had partial responses, and 4 had stable disease (response and stable disease, 100%), but all except one progressed within 10 months. Of the 12 patients who received chemotherapy during recurrence, there was 1 complete response, 2 partial responses, and 6 stable disease (response and stable disease, 75%), with long response duration and long survival (15-132+ mo). In the anaplastic mixed oligodendroglioma-astrocytoma group, 12 patients were treated at the time of the initial admission and 6 patients treated at the time of recurrence. The initial treatment resulted in two complete responses, three partial responses, and seven stable disease (response and stable disease, 100%), with most responses lasting longer than 12 months. The treatment of the patients with recurrent disease resulted in one partial response and five stable disease (response and stable disease, 100%), with a median time to progression of 6 months. These results suggest that aggressive treatment is beneficial for recurrent anaplastic oligodendrogliomas and mixed gliomas as well as initial mixed gliomas but may offer only minimal advantage over conventional radiotherapy for the initial treatment of anaplastic oligodendrogliomas. PMID- 8455761 TI - Relationship between tissue polyamine levels and malignancy in primary brain tumors. AB - We studied the relationship between tissue polyamine levels and malignancy in 146 primary brain tumors. Astrocytoma showed a consistent rise in levels of N1 acetylspermidine (N1-AcSpd) in tissue with increased grade of malignancy. Furthermore, in astrocytoma, the patients whose tumors contained high levels of N1-AcSpd (> or = 15 nmol/g) in tissue showed a far worse prognosis, a significantly lower recurrence-free survival rate, and a shorter survival rate than did the patients whose tumors contained lower levels of N1-AcSpd (< 15 nmol/g). High-grade astrocytoma contained N1-AcSpd at the level of 15 nmol/g or higher, and most of the benign brain tumors, including low-grade astrocytoma, meningioma, pituitary adenoma, and normal brain tissues contained much lower levels of N1-AcSpd. However, medulloblastoma, hemangiopericytoma, and neurinoma showed an inverse correlation between N1-AcSpd levels in tissue and biological malignancy. These results suggest that levels of N1-AcSpd in tissue can be a promising biochemical marker of malignancy in astrocytoma. In the other primary brain tumors, however, the relationship between levels of N1-AcSpd in tissue and biological malignancy should be examined in each histopathological type. PMID- 8455762 TI - Lumboperitoneal shunting: a retrospective study in the pediatric population. AB - There is a shortage of data concerning the long-term follow-up of patients with lumboperitoneal (LP) shunts, especially in the pediatric population. A retrospective study of 143 patients who underwent LP shunting between 1974 and 1991 was therefore performed. The mean age at the time of shunt insertion was 3.3 years (range, 18 d to 17.8 yr), and the indication for shunting was: hydrocephalus (81%), cerebrospinal fluid fistula (12%), and pseudotumor cerebri (7%). The mean follow-up time was 5.7 years (range, 5 d to 17.5 yr), and during this period, there were five deaths of which one was shunt related (2.5 yr post shunt insertion). Of the types of LP shunt used during the study period, the T tube shunt (101 patients) fared significantly better (P = 0.003) than the percutaneous type (42 patients), and the overall survival characteristics for the T-tube shunt approximated those seen for ventriculoperitoneal shunts, with a 50% probability of remaining free of malfunctions for 5 years. A high rate of migration (19%) was partially responsible for the poor performance of the percutaneous-type shunts. By the end of the study, 40 patients (28%) had been converted to ventricular shunts, and this rate of conversion was similar for both shunt types. LP shunts have certain advantages over other forms of cerebrospinal fluid diversion and were successfully used for various clinical conditions during this study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455763 TI - Spinal cord stimulation for chronic, intractable pain: experience over two decades. AB - Over the past two decades, spinal cord stimulation devices and techniques have evolved from single-channel systems, with electrodes requiring laminectomy, into programmable "multichannel" systems with electrodes that may be placed percutaneously. We have reviewed our experience in 320 consecutive patients treated with these devices at our institution between 1972 and 1990. Technical details of treatment as well as patient characteristics have been assessed as predictors of clinical outcome and of hardware reliability by univariate and multivariate statistical methods. Current follow-up has been obtained at intervals from 2 to 20 years (mean, 7.1 yr) postoperatively on 205 patients. All clinical outcome measures have been based on disinterested third-party interview data--standard analog pain ratings, employment status, activities of daily living, and use of analgesics. At 7-year mean follow-up, 52% of the 171 patients who received permanent implants reported at least 50% continued pain relief. A majority had maintained improvements in activities of daily living and analgesic use. Analysis of hardware reliability for 298 permanent implants revealed significantly fewer clinical failures (P < 0.001) and technical failures (in particular, electrode migration and malposition, P = 0.025) as single-channel implants have evolved into programmable, multichannel devices. Our analysis of technical and clinical prognostic factors may be useful to the clinician in selecting patients for this procedure. PMID- 8455764 TI - The Halifax Interlaminar Clamp for posterior cervical fusion: initial experience in the United Kingdom. AB - A retrospective review of patients who underwent posterior cervical stabilization with Halifax Interlaminar Clamps in four neurosurgical centers in the United Kingdom was performed. Satisfactory bone fusion without complication occurred in all patients in whom lower cervical spinal stabilization (C3-C7) was performed. Complications occurred in 14 of 45 patients undergoing atlantoaxial arthrodesis. In 10 patients, one of the screws loosened, and in 4 patients, one of the clamps disengaged; additional operations to achieve bone fusion were required in 9 patients (20%). The Halifax Interlaminar Clamp is safe and effective for posterior stabilization in the lower cervical spine; there is a significant failure rate associated with its use for atlantoaxial arthrodesis. PMID- 8455765 TI - Analgesia and sedation during percutaneous radiofrequency electrocoagulation for trigeminal neuralgia. AB - Patient comfort during percutaneous radiofrequency electrocoagulation for trigeminal neuralgia provides better working conditions for the surgeon and makes the patient more willing to return if a second procedure is necessary. This study evaluates five different regimens for analgesia and sedation including the standard of fentanyl and droperidol (Group A) and four other regimens, each containing midazolam. In a sixth group, droperidol was assessed for its antiemetic effects. Patients were medicated as follows: Group B, low-dose midazolam (3.0 mg average); Group C, low-dose midazolam (2.5 mg average) and oral diazepam (7.5 mg average) just before the procedure; Group D, high-dose midazolam (5.5 mg average); and Group E, high-dose midazolam (5.1 mg average) and oral diazepam. Medications were titrated to induce mild sedation in Groups A, B, and C and heavier sedation in Groups D and E. All patients received fentanyl and small doses of intravenous methohexital just before the cannula penetrated the foramen ovale and before radiofrequency electrocoagulation. At least 2 weeks later, patients reported their level of discomfort during the procedure and their recollection of the procedure on a 0 to 10 scale. In another group of 96 patients, 1.25 mg of droperidol was given in addition to the medications described for Groups D and E. There was a statistically significant improvement in comfort in Groups C, D, and E and added amnesia in Groups D and E. Vomiting occurred in none of the patients medicated with droperidol and in 5 of 143 patients who did not receive droperidol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455766 TI - Targeted brain biopsy: a comparison of freehand computed tomography-guided and stereotactic techniques. AB - With computed tomography (CT) and magnetic resonance imaging stereotactic systems, biopsies of intracranial lesions can be made with safety and ease. Before the development of this technique, neurosurgeons often performed freehand brain biopsies under CT guidance. While stereotactic biopsy is the procedure of choice for small, deep lesions, few studies have compared the morbidity, mortality, and efficacy in obtaining a diagnosis associated with these two techniques for superficial lesions. A total of 167 consecutive CT-guided or stereotactic brain biopsies were performed in 154 patients. Fourteen of the stereotactic and 12 of the CT-guided biopsies were of deep lesions and were excluded from analysis. The results of 75 freehand CT-guided biopsies of superficial lesions in 69 patients were compared with those of 66 stereotactic biopsies (34 CT-guided and 32 MRI-guided) performed with the Brown-Roberts-Wells stereotactic system in 60 patients. Twenty-five of the lesions in the stereotactic biopsy group measured < or = 2 cm, as compared with 13 of those in the freehand CT-guided biopsy group. There were no biopsy-related deaths among the patients who underwent freehand CT-guided biopsy and one death among those who underwent stereotactic biopsy (1.5%). Freehand CT-guided biopsy was associated with 5% morbidity, compared with 6% morbidity for stereotactic biopsy. Seven CT-guided needle biopsies (9%) and 12 stereotactic biopsies (18%) were nondiagnostic. Statistical analysis showed no significant difference between morbidity and mortality in the two groups, but the rate of diagnostic failure was significant (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455767 TI - Ocular tilt reaction resulting from vestibuloacoustic nerve surgery. AB - The ocular tilt reaction (OTR) is a triad of head-eye synkinesis composed of head tilt, conjugate ocular torsion in the direction of head tilt, and skew deviation. The OTR represents a normal compensatory response to lateral head tilts and is produced by activation of the utricle of the lowermost ear. A pathological OTR results when otolith activity is unopposed as the result of injury to the opposite utricle or its nerve. Vertical diplopia may be the only symptom of OTR in patients who have undergone surgery involving the vestibuloacoustic nerve. We report a series of patients with OTR after surgery for acoustic neuroma or Meniere's disease. In each patient, the manifesting symptom was vertical diplopia. Bedside neuro-ophthalmological testing readily excluded a brain stem cause for the double vision. We conclude that OTR after vestibuloacoustic surgery is a benign condition with spontaneous resolution of symptoms within several months. PMID- 8455768 TI - Radiosensitization and inhibition of deoxyribonucleic acid repair in rat glioma cells by long-term treatment with 12-O-tetradecanoylphorbol 13-acetate. AB - Patients with brain tumors often undergo radiotherapy, and the cellular resistance is a major obstacle. It has been suggested that protein kinase C (PKC) may be one of a number of important regulatory enzymes in cell response to ionizing radiation. We therefore investigated the effect of PKC depletion on deoxyribonucleic acid (DNA) damage and repair after radiation in C6 cells using a microgel electrophoresis method to explore the role of PKC in glioma radioresistance. When cells are embedded in agarose on slides, lysed, and subjected to an electric field, broken DNA is able to migrate toward the anode. A significant increase in the length of DNA migration was observed in the cells exposed to irradiation. Inhibition of PKC activity by prolonged treatment with 12 O-tetradecanoylphorbol 13-acetate (TPA) or staurosporine, a potent PKC inhibitor, before irradiation enhanced radiation-induced DNA damage and attenuated the repair of damaged DNA. The half-times of DNA repair in parent C6 cells and PKC depleted C6 cells were about 30 and 60 min, respectively, and the extent of DNA migration was still seen in the PKC-depleted cells even at 120 min after irradiation. In addition, the C6 cell clonogenicity after irradiation was also attenuated by long-term exposure of the cells to 12-O-tetradecanoylphorbol 13 acetate. These data suggest that PKC may play an important role in regulating the cell response to irradiation. The inhibitors of PKC might represent a new class of pharmacological agents to manipulate the radiosensitivity of gliomas. PMID- 8455769 TI - Application of photodynamic therapy to the treatment of atherosclerotic plaques. AB - Photodynamic therapy is a therapeutic modality long studies for its application to the treatment of malignant neoplasms. Recently, studies have suggested its potential use in the treatment of atherosclerosis. In this study, two atherosclerotic plaques were induced in the abdominal aortas of 35 rabbits. The animals then received Photofrin II (Quadralogic Technologies Inc., Pearl River, NY), a photosensitizer, at doses of 5 mg/kg and 2.5 mg/kg. After 48 hours, the plaques were irradiated by a fiberoptic connected to an argon ion laser. Fluency rates from 32 mW to 256 mW and energy doses from 1.6 to 60 joules were applied. Only one of the paired plaques was irradiated, the other remaining as a control. Four weeks after treatment, the vessels were assessed. Of 26 plaques treated with photodynamic therapy, 22 were no longer grossly visible, while the nine animals that received light irradiation but no Photofrin II all had visible plaque (P < 0.001). Studies of the vessel sections confirmed a reduction in intimal thickness from 0.74 +/- 0.15 mm in matched controls as compared with 0.51 +/- 0.13 mm in animals with treated plaques. There was a concomitant enlargement of the luminal diameter from 1.13 +/- 0.51 to 1.41 +/- 0.72. On the microscopic level, plaque reduction was most complete in the groups treated with 40 and 60 joules. Different fluency rates and drug dosages did not lead to differing outcomes. Our findings indicate that photodynamic therapy with dihematoporphyrin ether met our goal of reducing plaque size and may represent a means of treating atherosclerotic plaques. PMID- 8455770 TI - Mannitol, intracranial pressure, and vasogenic edema. AB - The effect of a 2 g/kg intravenous bolus of mannitol on intracranial pressure (ICP) and white matter water content was determined by following the time course of ICP and spatial white matter water content after administration of mannitol in a hemispheric cold lesion model of vasogenic edema in the cat. After mannitol infusion, maximal ICP reduction occurred at approximately 20 minutes and began to return to baseline after 26 minutes. White matter water content in the control hemisphere began to decrease much later, reaching a minimum at 60 minutes. White matter water content in the lesioned hemisphere was not changed significantly after mannitol infusion. We conclude that the rapid reduction of ICP after intravenous administration of mannitol is not solely due to the dehydration of white matter. PMID- 8455771 TI - Calcified brain metastasis. AB - Two patients with rare cases of calcified brain metastases are reported. The relatively benign clinical course and prolonged survival are stressed. The first patient had an adenocarcinoma of unknown origin with three calcified brain metastases. The patient underwent an incisional brain biopsy without radiotherapy and survived for 2 years and 9 months. The second patient had a squamous cell carcinoma of the lung with a large, solitary brain metastasis. The brain tumor was calcified and remained stable without progression for at least 4 months before surgical resection. PMID- 8455772 TI - Posterior fossa surgery: an unusual cause of superficial siderosis. AB - With the widespread use of magnetic resonance imaging, an increasing number of cases of superficial siderosis are being discovered. However, the cause remains uncertain in almost half the cases. We report a case where previous surgery for a pontine hematoma established a pathway for extravasation of blood into the 4th ventricle, resulting in superficial siderosis that was demonstrated on a follow up magnetic resonance imaging scan 8 years later. This case presents an unusual iatrogenic cause of superficial siderosis that has not been reported previously. PMID- 8455773 TI - Asymptomatic large hypothalamic hamartoma associated with polydactyly in an adult. AB - A hypothalamic hamartoma is a congenital tumor-like neural malformation. It is usually seen in children and is associated with neuroendocrinological symptoms, seizures, or psychological impairments. An asymptomatic hypothalamic hamartoma in an adult is extremely rare. This report describes an asymptomatic adult with a large hypothalamic hamartoma associated with polydactyly in his feet. Both polydactyly and hamartoma are rare lesions; therefore, this may not be a coincidental presentation. It is thought to have occurred in the embryonic period presumably between 37 and 40 gestational days. PMID- 8455774 TI - Intraventricular cavernous malformation associated with medullary venous malformation. AB - We reported a case of cavernous malformation (CM) associated with medullary venous malformation in the same area. The CM was located in the trigone of the lateral ventricle in the dominant hemisphere and drained into the longitudinal caudate vein of Schlesinger via deep medullary veins. By a transsylvian transventricular approach, the CM was totally removed with successful preservation of the medullary venous malformation. This approach is available for trigonal lesions, especially in cases with enlarged inferior horn. We stress that CM removal can be conducted with preservation of the adjacent medullary venous malformation. PMID- 8455775 TI - Direct endarterectomy of the middle cerebral artery for treatment of symptomatic stenosis: case report. AB - The authors report the clinical course and surgical technique used to treat a patient with a high-grade stenosis of the proximal middle cerebral artery that had caused a previous infarction and threatened the remaining dominant hemisphere. Trapping of the involved middle cerebral artery segment allowed direct exposure for excision of the atheromatous plaque and subsequent closure of the arteriotomy. Intraoperative angiography confirmed the reestablishment of flow. The patient made an uneventful postoperative recovery. Direct middle cerebral artery endarterectomy has the advantage of potentially reestablishing flow to lenticulostriate branches. The technique may also avoid the problem of occlusion at the site of maximum stenosis that can be caused by the use of an extra/intracranial bypass graft. Middle cerebral artery endarterectomy is a potentially valuable technique that deserves further investigation. PMID- 8455776 TI - Prolonged barbiturate therapy in a patient with closed head injury and jugular venous thrombosis. AB - The case of a patient who sustained a severe closed head injury complicated by jugular venous thrombosis is presented. Early problems with intracranial pressure were related to bifrontal intracerebral contusions. Jugular vein thrombosis became manifest clinically late in the patient's course and was verified by Doppler ultrasonography. Late problems with intracranial hypertension were presumed to be due to decreased cerebral outflow secondary to the thrombosis. The patient required 4 weeks of a high-dose regimen of pentobarbital to control his intracranial pressure. This is an exceptionally long period of time for a patient to be in barbiturate coma for a closed head injury and still make a satisfactory recovery. The incidence, etiology, prevention, and treatment of upper extremity and jugular venous thrombosis are discussed. The ramifications of jugular venous thrombosis in neurosurgical patients are discussed. PMID- 8455777 TI - Transcerebellar biopsy of posterior fossa lesions using the Leksell gamma model stereotactic frame. AB - We describe a technical modification of the Leksell gamma stereotactic system that enables a direct transcerebellar biopsy of posterior fossa lesions. By using an additional pair of long (14 cm) posts placed in the posterior positions of the frame, the frame can be positioned low enough to allow for direct approaches to the posterior fossa. With the patient in the semisitting position, a biopsy can be performed under local anesthesia. We have found this technique provides a simple, comfortable, and effective biopsy of posterior fossa lesions. PMID- 8455778 TI - A simple stereotactic retractor for use with the Leksell stereotactic system. AB - The author has designed a simple and inexpensive cylindrical stereotactic retractor that is compatible with the Leksell stereotactic system. The device allows the stereotactic localization and open resection of appropriate intracranial lesions through a 3-cm craniotomy, using standard microsurgical techniques and a completely sterile field. The device and its use are described. PMID- 8455779 TI - Middle cerebral artery occlusion in rats: a neurological and pathological evaluation of a reproducible model. PMID- 8455780 TI - Treatment options in primary Ewing's sarcoma of the spine: report of seven cases and review of the literature. PMID- 8455781 TI - Left and right hemisphere contribution to recovery from neglect after right hemisphere damage--an [18F]FDG pet study of two cases. AB - A 2-[18F]-Fluoro-2-Deoxy-D-Glucose ([18F]FDG) and positron emission tomography (PET) study was performed in the acute and chronic phase of stroke in one patient with unilateral neglect due to a right hemispheric lesion. In the acute phase, severe neglect, as well as hypometabolism in both the right and in the left unaffected cerebral hemisphere, was demonstrated. At follow-up evaluation the patient showed an almost complete recovery from unilateral neglect. This was associated with a return of left hemisphere metabolism to normal values and partial metabolic recovery in the right hemisphere, where frontal and parietal areas remained functionally impaired. Another patient with an extensive right cerebral ischaemic lesion on CT and severe unilateral neglect was studied by PET in chronic phase. A severe metabolic depression in the left unaffected hemisphere and in the right cerebral areas spared by the lesion, was found. These data suggest that the remission of unilateral neglect might be associated to a functional metabolic recovery in both the undamaged left hemisphere and the unaffected regions of the right hemisphere. PMID- 8455782 TI - Dual task performance by patients with left or right speech dominance as determined by carotid amytal tests. AB - Patients who had their speech dominance determined by carotid Amytal testing were evaluated with a dual task procedure consisting of reading and finger tapping. As expected, the asymmetry of interference between tasks varied with speech dominance. Patients with left hemisphere speech tended to show greater interference in the right hand whereas patients with right hemisphere speech showed greater interference in the left hand. Since the right hemisphere dominant patients were also right-handed, the results suggest that interference effects are more closely linked to speech than to motor dominance. PMID- 8455783 TI - Use of temporal context information in Alzheimer's disease. AB - Current theories of memory and memory dysfunction emphasize the importance of the use of contextual information in the storage and retrieval of specific episodes. Patients with lesions primarily in the diencephalon perform poorly on a measure of temporal recency, while those with temporal lobe amnesia are significantly better. The present study evaluated the ability of Probable AD patients to utilize information about temporal recency in the context of a recognition memory task. The performance of the AD patients was significantly impaired and resembled that of patients with Korsakoff's syndrome. The pattern of performance suggested that they were able to recognize which stimuli had been previously presented, but were unable to recall the correct temporal context. Further, there were no significant correlations between measures of temporal recency and those of frontal lobe function. These data suggest that AD patients, like other groups of patients with severe memory defects, are impaired at the use of context information in their attempts to remember recent events. PMID- 8455784 TI - The representation of patterns of structural brain asymmetry in normal individuals. AB - Hemispheric asymmetries were examined in 20 normal individuals who underwent MR scanning. The asymmetry indices were represented for a series of contiguous, consecutive coronal images through the occipital and frontal lobes, along the dorso-ventral [DV] axis. A monotonic decrease in size of the parieto-occipital hemispheric areal asymmetry was observed, from a marked left predominance to a greater degree of symmetry. When frontal and occipital lobe asymmetries were compared, the familiar frontal-right vs occipital-left counterclockwise torque was observed, but was found to be more prominent in the dorsal aspect of the frontal cuts and the ventral aspect of the occipital cuts. At the individual level, a within-subject linear model for predicting cerebral area as a function of cut, hemisphere and DV, revealed this marked DV effect. The use of the within subject linear model further enabled the individual assessment of structural asymmetries, and provided criteria by which subjects could be grouped. We further show how a deviation of the occipital falx will engender different hemispheric asymmetries, depending on the orientation of the coronal imaging plane. Given the latter, we recommend planning the coronal cuts based on a low-ventricular transaxial scout, wherein the deviated falx, if present, can be taken into account. PMID- 8455785 TI - Short-term memory impairments in Alzheimer-type dementia: evidence for separable impairments of articulatory rehearsal and long-term memory. AB - Two experiments are described which investigate the short-term memory deficits found in Alzheimer-type dementia. In the first experiment memory span for words of differing spoken duration is related to speech rate. Memory span was lower in subjects suffering from Alzheimer-type dementia than for normal elderly controls but in both cases a linear function related recall to speech rate for items of differing spoken durations. The function for Alzheimer subjects had an equivalent slope (interpreted as reflecting a contribution from a sub-vocal rehearsal process) but a lower intercept (interpreted as reflecting a contribution from a long-term memory component). The second experiment investigated the effects of repeating supra-span lists of items in a serial recall task. As predicted the control subjects showed substantial increases in recall across trials associated with elevations of the speech rate/recall functions while the Alzheimer subjects showed very little benefit from repetition of the lists. We conclude that the verbal short-term memory deficit found in Alzheimer-type dementia has two components: a deficit in the rate of rehearsal and an impairment in the long-term memory component of short-term recall. PMID- 8455786 TI - Expression is computed separately from facial identity, and it is computed separately for moving and static faces: neuropsychological evidence. AB - We report data contrasting the processing of facial identity from static photographs, and facial expression from static and moving images, in two patients with face processing impairments. One patient is markedly impaired at perceiving facial identity and he is poor at discriminating facial expression and gender from static photographs of faces. In contrast, he performs normally when required to make judgements of facial expression and gender to faces depicted by sets of moving light dots. The second patient is relatively good at perceiving facial identity, but poor at judging emotional expression from both static and moving faces. The data are consistent with the existence of separate processes for encoding face identity and facial expression, and, furthermore, indicate the separate encoding of expression from moving and static images. PMID- 8455787 TI - Effects of concurrent memory load on visual-field differences in mental rotation. AB - Normal right-handers mentally rotated letters flashed in the left or right visual fields under different conditions of working-memory load. In Experiment 1, the subjects held patterns of eight dots or sequences of eight letters in working memory, and these conditions produced a progressively increasing right visual field (RVF) advantage in rate of mental rotation relative to a control condition in which there was no load. Experiment 2 confirmed the shift toward increasing RVF advantage with a load of eight digits relative to two control conditions, one in which there was no load and another in which the subjects recalled digits before carrying out the mental rotation on each trial. These results are discussed in terms of the priming of the hemispheres by the concurrent loading of working memory. PMID- 8455788 TI - Effect of spatial attention on mental rotation. AB - Normal right-handed subjects performed a task requiring mental rotation of the letter R, presented in varying angular orientations in the left or right visual fields. They were told to attend to the side indicated prior to each trial by a centrally located arrow, while maintaining visual fixation on the arrow. On 75% of trials (compatible trials) the arrow pointed to the side of the letter, while on 25% (incompatible trials) it pointed to the other side. Although overall RT was shorter on compatible than on incompatible trials, there was no evidence that spatial attention affected mental-rotation rate. However, estimated rate was higher when attention was to the left side of space, consistent with right hemispheric specialization for mental rotation. This effect was especially marked when presentation of the letter was to the right. PMID- 8455789 TI - Cognitive and motor performance in multiple system atrophy and Parkinson's disease compared. AB - Nineteen patients with multiple system atrophy (MSA) of striato-nigral degeneration type were tested to examine cognitive and motor performance. Parkinson's disease (PD) patients and healthy subjects served as controls. The MSA and PD patients showed similar cognitive dysfunction and motor impairment, performing poorly in the visuo-spatial organization, the construction tests and motor assessment tests. Movement times were much longer in MSA than PD patients. The association of nigral with putaminal damage may explain the more severe bradykinesia in MSA. PMID- 8455791 TI - Paradigm shifts--What's good and not so good for health care. PMID- 8455790 TI - Left hemisphere strategies in visual recognition, topographical orientation and time planning. AB - Right hemisphere lesions are known to impair, in many cases, visual recognition and visuospatial orientation. We report here on the compensatory strategies used by a patient whose posterior part of the right hemisphere was either destroyed or visually deafferented. She presented a slight appreceptive agnosia, memory disorders, and severe topographical disorientation. Her strategy relied on detail by-detail analysis of buildings for recognition and on identification of landmarks and memorization of their sequences for finding routes. Time planning was impaired; the patient was unable to use a bi-dimensional timetable, but relied on a (linear) list of assignments. The linear, speech-related strategy she used was sustained uniquely by left hemisphere networks, since no processing of visual information occurred in the right hemisphere. PMID- 8455792 TI - Health care reform and nursing. PMID- 8455793 TI - Paralyzed by bigotry on AIDS. PMID- 8455794 TI - From the folks who brought you little red ribbons. PMID- 8455795 TI - Assisted suicide: where do nurses draw the line? AB - If a terminally or chronically ill patient chooses death, where does one draw the line between allowing suicide, encouraging suicide, assisting with suicide, or directly killing? How does one differentiate between injecting a consenting patient with a lethal injection for the purpose of causing death, from inserting the needle so that the patient may inject the lethal dose his or herself? Clearly there are differences between action, facilitation, encouragement, and mere information. PMID- 8455796 TI - Culture brokering as a model for advocacy. PMID- 8455797 TI - Tips on implementing the Patient Self-Determination Act. PMID- 8455798 TI - After HIV testing: what's next? PMID- 8455799 TI - Technology & nursing education. PMID- 8455800 TI - Lipid oxidation products in food and atherogenesis. AB - Lipid oxidation products are present in unknown amounts in the food supply of industrialized societies. Evidence for a putative role of some of these compounds in accelerating events in the atherogenic process--the initiation of endothelial injury, the accumulation of plaque, and the termination phase of thrombosis- comes from both animal and human studies. Although metabolic and epidemiological studies in humans and animals generally support the concept that a higher intake of polyunsaturates is beneficial to lipoprotein metabolism and cardiovascular health, some findings suggest that a diet high in polyunsaturated fatty acids that are insufficiently protected by antioxidants, such as vitamin E, may carry a higher risk of atherosclerosis. Although gross pathological effects of ingestion of lipid oxidation products are unlikely in the human feeding situation, more subtle metabolic actions of these compounds on vitamin E status, platelet activity, and lipoprotein metabolism cannot yet be discounted. The presence of reactive lipid oxidation components in foods needs more systematic research in terms of the metabolic effects of these compounds and their occurrence in the usual diet, as well as the associated antioxidant requirements. PMID- 8455801 TI - World declaration on nutrition. PMID- 8455802 TI - Vegetarian diets for treating nephrotic syndrome. AB - Vegetarian diets based on soy-protein appeared to be effective in treating the hyperlipidemia of nephrotic syndrome. Whether there is a unique effect of soy or whether all very low-fat, low-saturated-fat, low-cholesterol, and low-protein diets have similar effects remains unknown. PMID- 8455803 TI - The role of marine fish oils in the treatment of ulcerative colitis. AB - Recent studies suggest that marine fish-oil supplements, which are rich in n-3 fatty acids, may reduce the inflammation associated with ulcerative colitis. Fish oils may exert their beneficial effects by shifting eicosanoid synthesis to less inflammatory species or by modulating tissue levels of certain cytokines. PMID- 8455804 TI - Iron-deficiency anemia increases risk of preterm delivery. AB - In an inner-city sample of pregnant women, iron-deficiency anemia was associated with a higher risk of preterm delivery and low birth weight but not with small for-gestational-age births. However, the prevalence of iron-deficiency anemia (3.5%) explained only a small proportion of preterm deliveries. PMID- 8455805 TI - Growth patterns in the first year of life: what is the norm? AB - The use of reference standards, such as those of the National Center for Health Statistics (NCHS), for determining the health and nutritional status of breast fed infants and children has been questioned. A recent study found that the mean weight of formula-fed infants remained at about the 50th percentile throughout their first year, whereas that of breast-fed infants fell below the 50th percentile well before age one year. Although these children probably are not at nutritional risk, deviation from the national reference data could lead to unnecessary infant monitoring and testing as well as undue parental concern. PMID- 8455806 TI - Does supplemental arginine alter immune function following major surgery? AB - Provision to surgical patients of parenteral arginine with minimal additional calories did not enhance proliferation of mononuclear cells. Earlier reports of the immunostimulatory effects of arginine may reflect interactions between arginine and other dietary components rather than exclusive effects of supplemental arginine. PMID- 8455807 TI - Diet changes may aid vaginitis prophylaxis. PMID- 8455808 TI - Stress the 'obvious' in STD education. PMID- 8455809 TI - NP shares knowledge of constitutional short stature. PMID- 8455810 TI - Client-centered drug choice: an alternative approach in managing hypertension. AB - Despite adequate pharmacological alternatives, only a minority of individuals living with hypertension achieve normotensive blood-pressure levels. Numerous medical and behavioral strategies have been implemented in an attempt to increase adherence to therapeutic regimens. Most of these techniques have resulted in short-term adherence improvement and a high degree of relapse in the period following experimentation, making assessment of potential long-term benefits of therapy impossible. Regardless of the strategy selected, active patient participation has been consistently identified as a critical element in improving adherence. This article describes a new pharmacological management strategy for individuals with mild hypertension. This strategy allows individuals to sample different antihypertensive medications for a period of four weeks to six weeks and select their preferred drug of choice for hypertension management based on the individuals' subjective responses to therapy. When used with different beta blockers, this management approach has provided effective control of mild hypertension and has kept clients in therapy when other strategies have failed. PMID- 8455812 TI - An update on the diagnosis and management of pediatric asthma. Based on the National Heart, Lung and Blood Institute expert panel report. AB - Asthma morbidity and mortality are increasing despite the availability of antiasthma medicines and a broader understanding of the pathology of the disease. In an attempt to enhance the understanding of asthma and to aid in appropriate asthma management, the National Heart, Lung and Blood Institute assembled an expert panel, which developed a report titled "Guidelines for the Diagnosis and Management of Asthma." These guidelines are designed to facilitate patient and health-care-provider education, and diagnosis and management of asthma. Proper diagnosis of the disease is a frequent problem in children and adults. For proper diagnosis of asthma, a complete patient history, physical examination and specific laboratory tests are required. Health care providers who educate patients and their families about common symptom triggers, encourage avoidance techniques and who incorporate state-of-the-art treatment for acute and chronic asthma management may reduce the recent increases in asthma morbidity and mortality while maintaining normal growth and development of the child. PMID- 8455811 TI - Immunization strategies for the elimination of hepatitis B. AB - Rates of hepatitis B infection have remained high despite immunization programs for infants of HBsAg-positive mothers and individuals considered to be at high risk for exposure. The Centers for Disease Control and Prevention and the American Academy of Pediatrics have provided new recommendations for a comprehensive strategy to eliminate hepatitis B virus. The first priority is the prenatal screening of all pregnant women and follow-up vaccination of all infants. The second is the immunization of at-risk adolescents and adults. Ultimately, it is hoped that all adolescents will be immunized when feasible and that the incidence of hepatitis B virus infection will decline. Primary care providers have an important role in the provision of public education about hepatitis B and in the implementation of these new recommendations. PMID- 8455813 TI - Using State Board of Nursing data to estimate the number of nurse practitioners in the United States. AB - Knowing the number of nurse practitioners, both at the state and national levels, is important to those dealing with health care policy and education. To determine these numbers, we telephoned all state boards of nursing, and asked whether they distinguished nurse practitioners from other registered nurses and what the respective numbers were. Data were available from a time period beginning in March 1992 and ending in September 1992. Thirty-four states, representing 70.6 percent of all registered nurses, now distinguish nurse practitioners from other nurses. In these states, 1.35 percent of all registered nurses are nurse practitioners. Projecting this percentage to the states that do not make the distinction yields a total of 33,834 nurse practitioners in the United States. Using neighboring states rather than the national average as a predictor for no data states leads to a national total estimate of 31,294. When corrected for multistate licensure, the final estimated number is 27,226. This estimating method should yield even more accurate data in the future as more states certify and list their nurse practitioners. This method enumerates nurse practitioners as defined by the various states, which have highly variable definitions of what a nurse practitioner is. However, the variability in legal definition is decreasing as more states require national certification. PMID- 8455814 TI - Research on "feeding behavior": quantitative information vs. qualitative perceptions about where it is published. AB - To gain some understanding of where research on "feeding behavior" is published, a Medline search was conducted for the years 1980-1990 inclusive using the above key phrase to capture published articles coded in this way. Furthermore, an eight item questionnaire was mailed to all 451 persons listed in the 1990 membership directory of the Society for the Study of Ingestive Behavior (SSIB) soliciting views on the top five journals publishing the greatest number, as well as the most "prestigious," articles in this field, along with demographic information about the respondents. After deleting journals that published agriculturally based research relating to insects or parasites, the Medline search generated 1,813 articles in the top 25 journals, the top 5 of which were Physiology and Behavior (462 articles), Pharmacology, Biochemistry and Behavior (211 articles), Brain Research (118 articles), American Journal of Physiology (106 articles) and Brain Research Bulletin (87 articles). This fact accorded well with weighted scores generated from perceptions of SSIB respondents (24.4% return rate), whose top 25 rankings correlated highly (r14 = +0.829, p < .001) with the Medline data. Although the top 5 number 1 choices of "prestige" journals by SSIB members did not match up well with the Medline list, weighted "prestige" scores correlated reasonably well with the Medline data (r15 = +0.766, p < .001), but a bit less so with SSIB perceptions of where greatest numbers of articles appeared (r12 = +0.588, p < .05). Discussion is presented about the validity of these data, their implications, and their potential utility in helping researchers decide where to publish work in this field. PMID- 8455815 TI - Trends in place preference conditioning with a cross-indexed bibliography; 1957 1991. AB - The purpose of this work is to present a perspective of the conditioned place preference (CPP) test by offering an overview of the empirical research from 1957 1991. The intent is not to extensively analyze the controversies inherent to any behavioral technique but rather to present a survey of research using a descriptive statistics approach to explore topical issues. The objectives of this work are three-fold: (a) to provide an exhaustive bibliography of the CPP literature including articles, journal abstracts, book chapters and critical reviews; (b) to provide a cross-index of identified key words/drugs tested; and (c) to give an overview of selected procedural issues underlying CPP testing. PMID- 8455816 TI - The Flinders sensitive line rats: a genetic animal model of depression. AB - The Flinders Sensitive Line (FSL) rat, selectively bred for increased responses to the anticholinesterase DFP, was originally proposed as an animal model of depression because, like depressed humans, it is supersensitive to the behavioral and hormonal effects of cholinergic (muscarinic) agonists. The present review critically examines earlier and recent data collected on FSL rats to assess whether the model has good face, construct and/or predictive validity. With respect to face validity, FSL rats resemble depressed humans, at least superficially, in that they demonstrate: (a) reduced locomotor activity, (b) reduced body weight, (c) increased REM sleep, and (d) cognitive (learning) difficulties. So far, studies designed to assess the presence of anhedonia, a cardinal symptom of melancholic depression, have been inconclusive, but there are trends for the FSL rats to be more anhedonic than their control counterparts, the Flinders Resistant Line (FRL) rats, when exposed to chronic mild stress. Thus, FSL rats fulfill the criterion of face validity. Because FSL rats also are more sensitive to cholinergic agonists and have phase advanced circadian rhythms, they meet the criteria for the cholinergic and circadian rhythm models of depression and, therefore, have good construct validity. A key behavioral symptom exhibited by the FSL rat is demonstration of an exaggerated immobility when exposed to stressors such as foot shock and forced swimming. This behavioral abnormality has been normalized by a number of well-recognized antidepressant drugs such as imipramine and desipramine, as well as newer generation antidepressants with promising clinical effects such as sertraline and rolipram. However, several treatments that have not been routinely used to treat depression (lithium, exposure to bright light, the anticholinesterase DFP) have been ineffective in reversing the exaggerated immobility. Thus, the evidence in the present review indicates that the FSL rat model of depression fulfills the criteria of face, construct, and predictive validities. PMID- 8455817 TI - The stroboscopic patterns as dissipative structures. AB - Photic stimulation of the human visual system with uniform but intermittent illumination has been recognized for well over a century to give rise to the perception of complex visual patterns and forms. A review of the literature pertaining to these "stroboscopic patterns" is presented, along with a review of theories addressing their origins. The theories range from attributing the patterns to inhomogeneities in the structure of the eye, to the formation of functional domains of neural activity. A novel account of the origins of the patterns is developed in this paper utilizing advances in the neurobiology of information processing and nonlinear dynamics. This view conceptualizes the patterns as examples of "dissipative structures." These dissipative structures are conceived of as self-organizing macrostates of spatio-temporal coherence, widespread among visual cortical neurons. This self-organization is described in terms of nonlinear dynamics, in which sets of attractors emerge within a neural phase space undergoing constant change as the energy contained within successive volleys of stimulation-induced action currents is recursively dissipated by the visual system through cooperative feedback. The trajectories of activity formed by these attractors may reflect the actual form of the perceived patterns themselves and are thought to correspond to some of the reported properties of "linking fields" in the visual cortex. PMID- 8455818 TI - Behavioral effects of non-NMDA glutamate receptor antagonists. AB - Non-NMDA receptor antagonists decrease motor activity in some situations, alter the sleep-wake cycle, possess anticonvulsant and neuroprotectant actions, and appear to impair some learning tasks but not others. NMDA receptor antagonists affect these same functions but often in different and even opposite ways. NMDA receptor antagonists impair many different spatial learning tasks, including the Morris water maze, the Olton radial maze, and the hole-board task. Non-NMDA receptor antagonists are either ineffective in these spatial tasks or have not yet been evaluated. However, non-NMDA receptor antagonists may impair associative processes required in a bar-press response and in discrimination learning. Further research is needed in the context of comparing NMDA as opposed to non NMDA receptor antagonists within the same paradigm. PMID- 8455819 TI - Obesity, hyperlipidemia and non-insulin-dependent diabetes: a unified theory. AB - Obesity, hyperlipidemia, and non-insulin-dependent diabetes seem to share common causative factors, chemical abnormalities, and clinical complications. A positive energy balance requiring storage of excess nutrients as triglyceride appears to be an underlying factor in all. It is postulated that everyone has a defined capacity to store triglyceride. Filling the storage space from plasma glucose and triglyceride is insulin dependent. When storage areas are full, the effectiveness of insulin is reduced, and excess nutrients stay in circulation, producing the clinical picture of hyperlipidemia, non-insulin-dependent diabetes, and the shared findings. Comments about the implications of the model for the treatment of hypercholesterolemia, hypertriglyceridemia, and non-insulin-dependent diabetes are also incorporated. PMID- 8455820 TI - Prenatal malnutrition and development of the brain. AB - In this review, we have summarized various aspects as to how prenatal protein malnutrition affects development of the brain and have attempted to integrate several broad principles, concepts, and trends in this field in relation to our findings and other studies of malnutrition insults. Nutrition is probably the single greatest environmental influence both on the fetus and neonate, and plays a necessary role in the maturation and functional development of the central nervous system. Prenatal protein malnutrition adversely affects the developing brain in numerous ways, depending largely on its timing in relation to various developmental events in the brain and, to a lesser extent, on the type and severity of the deprivation. Many of the effects of prenatal malnutrition are permanent, though some degree of amelioration may be produced by exposure to stimulating and enriched environments. Malnutrition exerts its effects during development, not only during the so-called brain growth spurt period, but also during early organizational processes such as neurogenesis, cell migration, and differentiation. Malnutrition results in a variety of minimal brain dysfunction type syndromes and ultimately affects attentional processes and interactions of the organism with the environment, in particular producing functional isolation from the environment, often leading to various types of learning disabilities. In malnutrition insult, we are dealing with a distributed, not focal, brain pathology and various developmental failures. Quantitative assessments show distorted relations between neurons and glia, poor formation of neuronal circuits and alterations of normal regressive events, including cell death and axonal and dendritic pruning, resulting in modified patterns of brain organization. Malnutrition insult results in deviations in normal age-related sequences of brain maturation, particularly affecting coordinated development of various cell types and, ultimately, affecting the formation of neuronal circuits and the commencing of activity of neurotransmitter cell types and, ultimately, affecting the formation of neuronal circuits and the commencing of activity of neurotransmitter systems. It is obvious that such diffuse type "lesions" can be adequately assessed only by interdisciplinary studies across a broad range of approaches, including morphological, biochemical, neurophysiological, and behavioral analyses. PMID- 8455821 TI - Allergy-related quackery. PMID- 8455822 TI - Fertile field for fads and fraud. Questionable nutritional therapies. PMID- 8455823 TI - Health foods and supplements for the elderly. Who can say no? PMID- 8455824 TI - Sports nutrition fraud. PMID- 8455825 TI - The role of physicians in dental quackery. PMID- 8455826 TI - Reflections on the use of unproven arthritis remedies. PMID- 8455827 TI - Remedies for a society's debilities. Medicines for neurasthenia in Victorian America. PMID- 8455828 TI - The paradise of quacks. PMID- 8455829 TI - Kindly medicines. A history of the physio-medicals in American medicine. PMID- 8455830 TI - Diagnosis of occult primary rhabdomyosarcoma by magnetic resonance imaging. PMID- 8455831 TI - Coronary artery aneurysms. Case report and review of the literature. PMID- 8455832 TI - Immunoglobulin-A plasma cell dyscrasia in a young Hispanic man. PMID- 8455833 TI - Salmonella cholerasuis bacteremia and endocarditis in a patient with acquired immunodeficiency syndrome. PMID- 8455834 TI - Foamy histiocytes and lepra bacilli in a lymph node aspirate. PMID- 8455835 TI - False-positive mammographic imaging of a breast implant. PMID- 8455836 TI - Health fraud. PMID- 8455837 TI - Wolves in sheep's clothing. PMID- 8455838 TI - Combatting medical fraud. PMID- 8455839 TI - Recognizing deception in the promotion of untested and unproven medical treatments. PMID- 8455840 TI - AIDS fraud, finances, and fringes. PMID- 8455841 TI - The physician and cancer quackery. The physician's role in promoting the scientific treatment of cancer and discouraging questionable treatment methods. PMID- 8455842 TI - Ischemic stroke is predictable and preventable. PMID- 8455843 TI - Soft tissue sarcomas. Is adjuvant chemotherapy indicated? PMID- 8455844 TI - Quality of care problems among Medicare patients in New York State. AB - The Island Peer Review Organization is the peer review organization in New York State and is under contract with the Health Care Financing Administration to monitor the quality of care rendered to Medicare patients. A severity level III is assigned when a confirmed quality problem with significant adverse effects for the patient is confirmed. A severity level II is assigned when a confirmed quality problem with the potential for significant adverse effects on the patient is found. The purpose of this study was to retrospectively analyze all 85 severity level III citations and a 12% (223) random sample of the 1,880 severity level II citations for 1991. Another objective was to characterize the providers involved in each of these two levels of quality of care problems. Among the 85 severity level III citations, 34 (40.0%) involved premature death and 33 (38.8%) readmission. Treatment (45.0%), diagnostic (16.9%), and monitoring (16.4%) problems accounted for 78.3% of the 189 problems identified in severity level III citations. The leading problem areas were the treatment of infections and the use of antibiotics (21.2%), fluid and electrolyte management (21.2%), drug use (9.4%), the use of endotracheal tubes (5.9%), the management of diabetes mellitus (5.9%), and the management of hematologic disorders (5.9%). Attending physicians (65.9%), nursing departments (16.5%), and resident physicians (7.1%) were involved in the vast majority (89.5%) of severity level III citations. Treatment problems comprised 60.5% of the 243 problems found in severity level II citations, followed by inadequate work-up (20.2%), and incomplete documentation (12.3%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455845 TI - Perioperative stroke after general surgical procedures. AB - Perioperative cerebrovascular accidents after general surgical procedures are rare, but devastating and often fatal. The purpose of this study was to identify the perioperative, intraoperative, and postoperative factors associated with perioperative strokes after general surgical procedures. Over a five-year period, 19 patients of 24,641 general and vascular surgical procedures (0.08%) suffered a perioperative stroke. Patients undergoing carotid endarterectomies were excluded. These 19 patients were compared with a group of 19 patients matched for age and procedure. The strokes occurred in relation to the surgery as follows: 53% within 24 hours, 31% within one to seven days, and 16% within seven to thirty-six days. The overall perioperative mortality was 26%. In long-term follow-up, four patients died, two had complete recovery (11%), two had 90% recovery (11%), one had partial recovery (5%), and one remained completely disabled (5%). In comparing the groups, the significant factors contributing to perioperative stroke included hypertension, smoking, earlier neurological symptoms, and an abnormal rhythm on electrocardiogram. The most common factor for stroke was atrial fibrillation. Only one patient had an intracerebral hemorrhage. Although the exact mechanism of perioperative stroke remains uncertain, its association with abnormal cardiograms, lack of association with carotid bruits, and lack of intracerebral hemorrhage all suggest that emboli from the heart is the major cause in most patients. These data indicate that a perioperative stroke is associated with a very high mortality rate (26%) and is a potentially predictable complication in the majority of patients. PMID- 8455846 TI - Compliance with New York State's do-not-resuscitate law at Memorial Sloan Kettering Cancer Center. A review of patient deaths. AB - We reviewed the case records of 141 patients (134 with cancer and seven with acquired immunodeficiency syndrome) who died at Memorial Sloan-Kettering Cancer Center between July 11 and September 19, 1991. Do-not-resuscitate orders had been written on 115 (85.8%) of the patients with cancer and all of the patients with acquired immunodeficiency syndrome. The do-not-resuscitate orders appeared to be valid, in that evidence of informed consent was documented in all but two of the cases. Six additional patients who died had family consent not to resuscitate, although no do-not-resuscitate orders were written. Two other patients died unexpectedly. The remaining 11 patients all received aggressive attempts at resuscitation, which were felt to be medically appropriate in all but two cases. The interval between the do-not-resuscitate order and death was between zero and 60 days, with an average of 8.4 days and a median of 6 days; it exceeded 20 days in 14 cases. We attribute the high degree of compliance with the New York State do-not-resuscitate law observed in this study to an intensive program of consultation and education begun in 1987 by the Ethics Committee of Memorial Sloan-Kettering Cancer Center. PMID- 8455847 TI - Fetal tissue research and transplantation. PMID- 8455848 TI - Joseph Peter Hoguet, MD. A courageous New York surgeon. PMID- 8455849 TI - Medical spoons. A brief look at patents of the 1870s and 1880s. PMID- 8455850 TI - When death restores life. PMID- 8455851 TI - Home care. Doing right for the wrong reason. PMID- 8455852 TI - Bilateral, symmetrical leiomyosarcoma of the lower extremities. PMID- 8455853 TI - Ganglioglioma of the mastoid region: a case report. PMID- 8455854 TI - Remember when. PMID- 8455855 TI - Physicians in distress. PMID- 8455856 TI - Lead screening. PMID- 8455857 TI - Munchausen syndrome. PMID- 8455858 TI - [Nurses and figures]. PMID- 8455859 TI - [Dealing with upsetting behaviors in long-term care]. PMID- 8455860 TI - [Experimenting with massage in a home for the aged]. PMID- 8455861 TI - [Respect for the rights of the residents; a question of competence]. PMID- 8455863 TI - [Repeated grievings]. PMID- 8455862 TI - [The musical vigil. A unique project in palliative care]. PMID- 8455864 TI - [Sociosanitary dynamics in Zimbabwe]. PMID- 8455865 TI - [My mother is going to die...]. PMID- 8455866 TI - [At Rimouski: an innovative program in nursing sciences]. PMID- 8455867 TI - Cartoons: glimpsing paradoxical moments. PMID- 8455868 TI - The theory--research--practice triad. PMID- 8455869 TI - The science of unitary human beings and interpretive human science. AB - Natural science and human science are identified as the bases of most nursing theories and research programs. Natural science has been disclaimed by Martha Rogers as the philosophy of science that undergirds her work. The question remains, is the science of unitary human beings an interpretive human science? The author explores the works of Rogers through a dialectic with two human scientists' works. Wilhelm Dilthey's works represent the founding or traditional view, and Jurgen Habermas' works represent a contemporary, reconstructionist view. The ways Rogerian thought contributes to human studies but is distinct from traditional and reconstructionist human sciences are illuminated. PMID- 8455870 TI - Dialectics and the diverse discourse in nursing science. PMID- 8455871 TI - Learned helplessness as an interacting variable with self-care agency: testing a theoretical model. AB - This article describes the theoretical development and initial testing of a model outlining the interaction of the concepts of self-care agency and learned helplessness in healthy working adults. Orem's theory of self-care and the reformulated learned helplessness theory are discussed as the theoretical basis for the study. The self-care agency conditioning factors, age and gender, were examined for relationships to the main variables. In a descriptive, correlational design, the hypothesis, that learned helplessness was inversely related to self care agency, was supported (r = -.57). Neither age nor gender was related to main variables in the population. Implications for nursing research, self-care theory clarification, and nursing practice are discussed. PMID- 8455872 TI - The experience of laughter: a phenomenological study. AB - The purpose of this research was to uncover a structural definition of laughing in persons over 65. The structural definition that arises from this study is: laughing is a buoyant immersion in the presence of unanticipated glimpsings prompting harmonious integrity which surfaces anew through contemplative visioning. This definition is congruent with some of the current literature and practices related to laughter and health. It corresponds to the principles of Parse's human becoming theory and thus expands understanding of human experiences related to structuring meaning, living in relation to others, and viewing the familiar in a new light. PMID- 8455873 TI - Living paradox in Parse's theory. AB - Paradox has been of interest to humankind since ancient times. More than a decade ago Rosemarie Rizzo Parse specified paradoxical patterns of human relating in her nursing theory man-living-health. Since that time there has been increasing recognition by nurse researchers that paradox is an inherent aspect of human experience and an important dimension of health. The purpose of this article is to describe the phenomenon of living paradox as an inherent aspect of human experience and health. The author explores the historical development of paradox, along with its various forms and uses. Living paradox is defined as a rhythmical shifting of views, the awareness of which arises through experiencing the contradiction of opposites in the day-to-day relating of value priorities while journeying to the not-yet. The author demonstrates that living paradox as specified in Parse's theory of human becoming (formerly man-living-health) is a significant contribution to nursing and human science. PMID- 8455874 TI - Virtual reality: a new vista for nurse researchers? PMID- 8455875 TI - Case management and nursing theory-based practice. PMID- 8455877 TI - Holding the baby. PMID- 8455876 TI - Nursing the nation. PMID- 8455878 TI - Incontinent patients take part in test. PMID- 8455879 TI - Nursing initiative pinpointed problem. PMID- 8455880 TI - Speaking for students. Interview by Teresa O'Connor. PMID- 8455881 TI - Parallel path begins. PMID- 8455882 TI - Discipline and disability. PMID- 8455883 TI - Fiona's adjournment. Interview by Kathy Stodart. PMID- 8455884 TI - Pitfalls in America. PMID- 8455885 TI - New needles designed to protect personnel. PMID- 8455886 TI - New assessment instrument proposed for nursing facility residents. PMID- 8455887 TI - Legal update for nurses--1992: Part III. PMID- 8455888 TI - Creating moral space for nurses. PMID- 8455889 TI - Why an IS business plan? Information service. PMID- 8455890 TI - Nursing, health care prevention and political influence: a winning combination. American Organization of Nurse Executives. PMID- 8455891 TI - Communication: coping with the unspoken dance. AB - During an all-day retreat, a psychiatric nursing staff identified its patient care mission and interpersonal behaviors which inhibited accomplishing it. Collaborating with managerial interventions, staff members learned how to communicate in their practice environment effectively to their own benefit and that of their patients. PMID- 8455892 TI - Management techniques: coping with difficult people. PMID- 8455893 TI - Say the words: communication techniques. AB - Communication pathways develop techniques needed to accomplish work in a professional, productive and comfortable manner. Open, honest communication and active listening alleviate stress, lack of recognition and burnout. PMID- 8455894 TI - Ten steps to effective persuasive speaking. AB - A proven, 10-step system persuades audiences to change their attitudes, beliefs and feelings. Effective words, congruent with confidence and preparation, successfully maximize outcomes. PMID- 8455895 TI - Interpretation of group behavior. AB - A Systematic Multiple Level Observation of Groups (SYMLOG) allows managers to graphically see how their perception of personal behavior compares with their colleagues' views of the same behavior. Through recognition and awareness, groups can change ineffective behavioral patterns. PMID- 8455896 TI - Costing services: comparing three i.v. medication systems. AB - Three methods of intermittent intravenous (IV) medication delivery were studied for evidence of cost effectiveness. Eighty-five patients receiving antibiotics on two general medicine units were examined over an eight-week period. Chi square analysis revealed no significant differences in the number of IV complications among the three delivery systems. ANOVA revealed no significant differences among the three systems. A cost savings of $99.70 per patient using the Bard system and $98.60 using the BD system was realized. Thirty-six (88%) of the nurses preferred a syringe pump system, 10 patients showed no strong preference for any of the methods, and the two pharmacists preferred a syringe delivery system. PMID- 8455897 TI - Response to innovation: behavioral patterns. AB - An innovation model describes behavior patterns and the specific responses these groups display when introduced to change. These six categories, which are not inclusive, extend along a continuum ranging from eager participation to outright rejection of change. Using this knowledge, the nurse manager can team up with certain group types to smoothly implement innovation into the system. PMID- 8455898 TI - Critical care unit design, Part III: Establishing operations. AB - Last-minute details are checked and rechecked as a new critical care unit moves into its final phase of development. Adequate preparation involving orientation, education, budgets and open house activities assures a smooth transition. PMID- 8455899 TI - Best of both worlds: part-time nurse managers. AB - Begun as a temporary measure due to resignation of nurse managers on two units, utilization of two qualified part-time nursing supervisors already on the staff resulted in initiation of a new career opportunity. Productivity, morale and goal attainment were ensured and staff accountability and empowerment increased. PMID- 8455900 TI - Using the mission statement to craft a least-restraint policy. AB - St. Peter's Hospital used the Mission Statement as a foundation upon which to build a new "Least Restraint Policy." The Mission Statement guided the change process by assisting us to 1) identify the need for change, 2) identify the values and beliefs on which a new policy should be based, 3) identify the need for interdisciplinary planning, and 4) identify the need for staff and family education before implementation of the new policy. PMID- 8455901 TI - Career scope--North Central. PMID- 8455902 TI - "I know you think you heard...". PMID- 8455903 TI - ICRP 60--the next step. PMID- 8455904 TI - Radiopharmaceutical licensing revisited. PMID- 8455905 TI - Radiation dose rates from adult patients receiving 131I therapy for thyrotoxicosis. AB - Recommendations for restricting the exposure to radiation of members of the public coming into contact with thyrotoxic patients treated with 131I are currently based on the activity retained by the patient, and not on the doses likely to be received by such individuals. In order to examine whether these current implications of a reduction in this limit to 1 mSv, measurements were made of the dose rates at distances of 0.1, 0.5 and 1.0 m from 60 patients just before they left the nuclear medicine department. These measurements were repeated 1, 3, 6, 8 and 10 days after administration for 30 patients, and the radioactivity in samples of saliva taken on each of these days and secreted in sweat over the first 24 h were also measured. Doses were estimated for administered activities of approximately 200-600 MBq, assuming appropriate values for the times and distances spent near other individuals while travelling, at work, at home and near to young children considered in three age groups (< 2, 2-5 and 5-11 years). Periods of restriction were derived which would reduce these doses to 5 or 1 mSv. For a dose limit of 5 mSv, there is no need to restrict private travel, public transport journeys can last up to 7 h, a patient can return to work immediately, but sleeping with a partner will have to be restricted even for the minimum activity of 200 MBq.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455906 TI - Reliability of ACE inhibitor-enhanced 99Tcm-DTPA gamma camera renography in the detection of renovascular hypertension. AB - Twenty consecutive patients with renovascular hypertension, proven by cure or improvement of hypertension at 1-year follow-up after percutaneous transluminal angioplasty or surgical repair, were studied before intervention by means of gamma camera renography with 99Tcm-diethylenetriaminepentaacetic acid (99Tcm DTPA) at baseline and after angiotensin-converting enzyme (ACE) inhibition. Sixteen patients underwent bilateral renal vein catheterization for measurement of renal vein renin release and extraction ratios of para-amino-hippurate (PAH) and 51Cr-EDTA before and after acute ACE inhibition. With the limit for a significant change in relative side distribution of 5% or more after ACE inhibition on gamma camera renography 13 patients responded (Group 1), while seven patients (Group 2) had unchanged side distribution. Glomerular filtration rate (GFR), measured with 99Tcm-DTPA, in the affected kidney decreased in Group 1 from 26 +/- 16 ml min-1 to 11 +/- 12 ml min1 (P < 0.0005), while GFR was unchanged in the affected kidney in Group 2, 26 +/- 13 ml min-1 versus 29 +/- 13 ml min-1. Extraction ratios of PAH and 51Cr-EDTA for the affected kidney in Group 1 decreased from 80 +/- 18 to 73 +/- 21% (P < 0.05) and from 16 +/- 5 to 7 +/- 5% (P < 0.005), respectively, while in Group 2 the PAH extraction ratio was not significantly changed, 86 +/- 5 versus 81 +/- 14%, but the 51Cr-EDTA extraction ratio for the affected kidney also decreased from 16 +/- 3 to 8 +/- 4% (P < 0.005). All patients had lateralization of renal vein renin to the affected kidney.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8455907 TI - Computer-derived regions of interest for the determination of renal parenchymal transit time. AB - Renal parenchymal transit time measurements are used in the diagnosis of obstructive nephropathy but parenchymal regions are usually drawn by hand with or without the aid of a functional image. This paper describes three computerized methods for derivation of parenchymal regions from a mean time functional image and compares them with the manual method by processing renogram data from 82 normal, 19 obstructed and 11 dilated nonobstructed kidneys using all four techniques. Receiver-operator characteristic analysis demonstrated the computer methods to be superior to manually drawn regions. The optimum computer method had a sensitivity of 95% and specificity 95% for distinguishing obstructed kidneys from dilated nonobstructed kidneys. The computer method could be readily incorporated into routine renogram analysis programs. PMID- 8455908 TI - 123I-labelled BMIPP fatty acid myocardial scintigraphy in patients with hypertropic cardiomyopathy: SPECT comparison with stress 201Tl. AB - 123I-labelled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) myocardial single photon emission computed tomography (SPECT) was performed in 17 patients with hypertrophic cardiomyopathy, and was compared with 201Tl exercise stress myocardial perfusion SPECT images. Fourteen patients showed asymmetrical hypertrophy, and three demonstrated apical hypertrophy. SPECT was performed 20 min and 3 h after injection of 111 MBq 123I-BMIPP at rest. Exercise stress 201Tl SPECT was performed at 10 min and 3 h after injection and was compared with BMIPP imaging. In 13 patients BMIPP accumulation in the hypertrophied area in the 20 min image was lower than that of 3 h 201Tl uptake. Interestingly, six patients demonstrated 201Tl redistribution in the region where the uncoupling of BMIPP uptake at 20 min and 201Tl accumulation at 3 h after exercise was observed. These findings suggest that impaired fatty acid metabolism or utilization in hypertrophic myocardium and ischaemia or impaired coronary flow reserve may be one of the causes of the abnormality of fatty acid accumulation. PMID- 8455909 TI - Bone mineral density measured by dual photon and dual energy X-ray absorptiometry: a problem of accuracy. AB - Dual photon absorptiometers (DPA) are currently being replaced by dual energy X ray absorptiometers (DXA) for measurements of bone mineral density (BMD). In order to evaluate how to use the previously obtained BMD results by DPA (BMDo) in the follow-up of patients, the following study was performed. Ninety-five women who had had BMDo during the last 12 months were selected. L2-L4 BMD was measured twice on the same day using both DPA (BMDp) and by DXA (BMDx). BMDp was highly correlated to BMDx (R = 0.95; P < 0.001) but a wide variation of the ratio BMDp:BMDx was observed which ranged between 0.65 and 1.09 (mean 0.90, S.D. 0.05). There was no significant relationship between the ratio BDMp:BMDx and age or height but there was a significant relationship between this ratio and the weight of the patient (R = 0.31; P < 0.001). The results also indicated that the correlation between DXA and DPA was lower than that observed between the two DPA measurements (R = 0.98; P < 0.001) which, moreover, were not performed on the same day. These observations contrast with the relatively high precision of both instruments and have to be attributed to relative inaccuracy of one or probably both techniques. PMID- 8455910 TI - The role of radionuclide studies in breast cancer. PMID- 8455911 TI - Measurement of colonic transit time using radionuclide imaging: analysis by condensed images. AB - A polymer-coated capsule has been used in eight volunteer subjects to deliver 111In-resin into the ileocaecal region. The images were acquired for up to 3 days to follow transit through the colon. Expressing the results of individual studies is difficult and time-activity curves for each region are confusing. Calculation of the geometric centre indicates only where the middle of the activity has reached. We describe a new method of presenting colonic transit data as parametric images. The parametric images show the amount of activity in each area of interest as the study progresses. This is readily understood and allows segmental movement of the isotope, either forward or retrograde, to be examined. The geometric mean of activity in four areas of the colon were also calculated. Four hours after reaching the ileocaecal region, 65% (S.D. 24%) of the activity was in the caecum and 26% (S.D. 20%) in the transverse colon. By 24 h three controls had excreted most of the activity, in two the activity was mainly in the rectum and in two there was still some activity in the transverse colon. A protocol for colonic transit studies, problems with analysis and a new method of presentation of data are discussed. PMID- 8455912 TI - Diabetic foot infections: scintigraphic evaluation with 99Tcm-labelled anti granulocyte antibodies. AB - Thirty-eight lesions found by physical and/or radiological examination in 25 patients with long-term diabetes mellitus were studied in order to evaluate the clinical utility of immunoscintigraphy using 99Tcm-labelled anti-granulocyte monoclonal antibodies (MAb BW 250/183) for the diagnosis of infectious pathology in diabetic foot. All the patients underwent three-phase bone scintigraphy with 740 MBq 99Tcm-methylene disphosphonate. Immunoscintigraphy was performed 4 and 24 h after administration of 500 MBq of the labelled antibody by planar selective views. Uptake intensity was scored 0 to 4 (0 = normal, 1 = mildly increased, 2 = moderately increased, 3 = intense, 4 = very intense) when compared with adjacent or contralateral uninvolved bone marrow and soft tissue. Several projections were performed and anatomical references of bone scan were used to determine whether the lesion involved the bone or soft tissue. Definitive diagnoses were 15 osteomyelitis, 14 soft tissue lesions (nine cellulitis and five noninfected ischaemic or trophic wounds), and nine degenerative bone disease. 99Tcm granulocyte scintigraphy showed increased uptake in seven soft tissue lesions, in four of which exclusively soft tissue involvement was demonstrated by scintigraphy. Only one false negative scintigraphic finding was observed (chronic osteomyelitis). No abnormal anti-granulocyte antibody uptake was observed in degenerative lesions. Based on our observations, immunoscintigraphy with 99Tcm MAb BW250/183 has a sensitivity of 93% in the diagnosis of osteomyelitis involving diabetic patients' feet. Although it is feasible to distinguish exclusive soft tissue involvement, this is still the main cause of misdiagnosis in current clinical practice. PMID- 8455913 TI - A better target-to-background activity ratio using a large-sized colloid compared to a nano-sized colloid for scintigraphy of the peripheral bone marrow. A study in mice and humans. AB - Small-sized radiocolloids with a diameter less than 100 nm (nanocolloids), reduce the confounding liver and spleen uptake compared to large-sized colloids at bone marrow scintigraphy. Consequently, nanocolloids are today generally used for this purpose. Such colloids, though, seem to produce considerable background activity, especially from the large vessels and the urinary tract. This has been studied in mice and humans using a nanocolloid and a large-sized colloid, both composed of human albumin. In mice, the findings confirm a lower relative and absolute uptake of the nanocolloid in the liver and spleen compared to the large-sized colloid, whereas the bone marrow activity relative to the activity of kidneys, heart, lungs, intestines and peripheral blood is higher for the large-sized colloid than for the nanocolloid. The latter was confirmed in humans who were examined by single photon emission computed tomography corrected for attenuation and scattering of photons. It is concluded that a large-sized colloid should be used for spot examination of a specific marrow region outside the liver and spleen, while a nanocolloid must be used when examining structures close to the liver and spleen as well as for depiction of the entire bone marrow. PMID- 8455914 TI - Detection and quantitative analysis of joint activity inflammation with 99Tcm polyclonal human immunoglobulin G. AB - 99Tcm-polyclonal human immunoglobulin G (HIG) scintigraphy was used to detect active joint inflammation and to obtain ratios of joint uptake in noninvolved and inflammatory joints. Imaging was performed at 4 and 24 h in 16 patients with rheumatoid arthritis (RA) and 16 with degenerative joint disease (control group). All joints (total of 1344) were scored for pain, swelling and visual analysis of uptake in both scans. Joint to background (J:B) ratios were also calculated. Clinical and visual scores correlated in both scans (r = 0.7, P < 0.01). In RA patients, 246 joints were clinically involved. Visual analysis of scans detected 213 (87%) of them at 4 h and 196 (80%) at 24 h. Joints with no pain or swelling showed significantly higher J:B ratios than the control group and lower ratios than joints clinically involved. In the control group, statistically significant differences in J:B ratios between the various joints were found, so it was necessary to establish a normal range for every joint. J:B ratios were significantly higher at 4 h than at 24 h in both groups of patients. 99Tcm-HIG scintigraphy allows detection and measurement of joint inflammation. Scans performed at 4 h are preferable to scans at 24 h. Quantitative analysis can measure more objectively the degree of activity and could be useful in the management of these patients. PMID- 8455915 TI - Misadministration of radioactive material in medicine. PMID- 8455916 TI - Proportion of injected dose of isotope received by children in dynamic renal scanning. PMID- 8455917 TI - An account of the usefulness of a pilot clinical ethics program at a community hospital. AB - This article describes the development and implementation of a six-month pilot clinical ethics program at Saint Thomas Hospital (Nashville, Tenn). To assess the impact of this program, baseline data were gathered from a self-selected sample of critical and special care unit nurses and physicians about the "most troublesome" ethical dilemmas in their practices. Nurses and physicians reported facing similar dilemmas in practice. Nurses believed that chaplains and peers were most "beneficial" in resolving their "most troublesome" cases; physicians did not deem one particular individual or service to be of any greater benefit than any other in dilemma resolution. Nurses and physicians indicated that in many cases patients and families did not appear involved in the process. In a posttest survey following the pilot program, nurses rated the beneficial role of chaplains somewhat lower and agreed that the clinical ethics service was beneficial. As with the pretest sample, the posttest nurses evaluated the role of the attending physician as "detrimental" to resolving their ethical conflicts. In the posttest, physicians ranked the role of the clinical ethicist as comparable to that of chaplains and social workers. PMID- 8455918 TI - The year in review in QRB: works in progress. PMID- 8455919 TI - Outcomes management and continuous quality improvement: the compass and the rudder. PMID- 8455920 TI - The critical path method in stroke rehabilitation: lessons from an experiment in cost containment and outcome improvement. AB - This study tested the effects of a project network technique called the Critical Path Method (CPM) on the costs and outcomes of inpatient team stroke rehabilitation. On admission to a large, academic, inpatient rehabilitation hospital adults who had a recent (< 120 days) stroke were randomly assigned to receive rehabilitation services from a team trained in CPM (N = 53) or from usual care teams (N = 68). Results showed no significant difference between groups in length of stay, hospital charges, or functional status at discharge. CPM may be effective in patient care services that are less influenced by specialization, professional issues, and external regulation and in settings where patient outcomes are relatively fixed and predictable, and medical care is integrated across institutions. PMID- 8455921 TI - [Surgical indication for hip endoprosthesis]. AB - The authors give a short review of the history, development, results of the joint endoprosthetic, regarding mainly to the hip replacement, based on their own data and on international references. It is suggested that the development of the modern surgical technique changed the condition of the indication which needs a wide publicity. PMID- 8455922 TI - [Determination of the functional state of the uterine tube by hysteroscopy]. AB - The authors present their observations on the uterine os and signs of patency of the Fallopian tubes based on 240 cases of infertility examined by hysteroscopy. The shape of the cornual region, the adjacent pathological structures, ie., adhesions, polyps, fibroids etc., the outflow of the distending medium towards the Fallopian tubes and the movement of the tubal os were visualised. Intrauterine pressure and flow data were recorded in order to judge tubal patency. The funnel-shaped (in contrast with the flat type) cornual region, rhythmic contraction of the tubal os, the outflow of distending medium, intrauterine pressure under 100-120 Hgmm and standard 25-50 ml/min medium flow were evaluated as characteristic diagnostic signs of tubal patency. PMID- 8455923 TI - [Informative morphogenetic variance in children with acute lymphoid leukemia and in members of their families]. AB - Earlier studies suggested an increased prevalence of minor morphological aberrations and variants, also termed informative morphogenetic variants (IMVs) in children with acute lymphoblastic leukaemia (ALL) and possibly in their siblings, however, family investigations have not been performed in this field. In the present survey the occurrence of 54 well-defined IMVs was determined in 50 children with ALL, in their 53 siblings, 49 mothers, and 41 fathers. 170 children examined for acute infections served as controls. A significantly increased prevalence on IMVs was found in the ALL-patients and in their siblings: their IMV/subject ratios were 1.32 and 1.38, respectively, whereas the same parameter was 0.75 in the mothers, 0.66 in the fathers, and 0.76 in the controls. The same tendency was observed when familial cases and/or age-dependent IMVs were excluded. No association of ALL with given specific IMVs or combinations was found. On the basis of an increased prevalence of minor morphological aberrations no conclusion concerning predisposition to ALL or any other malignancy can be drawn at the moment. However, further investigation of the problem is justified, since the research of such association may reveal new details of prenatal origin and predisposition of childhood malignancy. PMID- 8455924 TI - [Right coronary--right ventricular fistula as a complication of myocardial biopsy]. AB - In the past decade myocardial biopsy has become a routine diagnostic procedure in cardiology. One of the potential complications is coronary artery--right ventricular fistula. The authors present a case of development and gradual enlargement of a iatrogenous fistula in a heart transplant recipient. PMID- 8455925 TI - [Inverted sigmoid diverticulum simulating polyps]. AB - The authors write about the inversion, a rare complication of the diverticulum of the sigmoid colon. The colour, surface of the diverticulum, 15 and 8 mm in diameters, were the same as the colon mucosa, it was soft and mobile by tacting. Biopsy was performed which caused a serious complication, a perforation to the free abdominal space, requiring a surgical operation. The inverted diverticulum can be distinguished from a polyp not by endoscopy, but by double contrast barium enema. Detecting a long, soft, mobile mass in the colon, must be thought about an inverted diverticulum and the biopsy must be omitted. PMID- 8455926 TI - [History of abortion laws]. PMID- 8455927 TI - [Hungarian variant of the 1817 tragedy of the English Princess Charlotte--data on the curriculum of the first Hungarian professor of obstetrics]. PMID- 8455928 TI - Activation of c-mos oncogene by integration of an endogenous long terminal repeat element during transfection of genomic DNA from mouse skin tumor cells. AB - An activated c-mos oncogene was identified in a transformed clone of golden hamster embryo cells transfected with DNA extracted from cells cultured from a UV induced mouse skin tumor. Southern blot hybridization with a v-mos oncogene probe showed that the mos oncogene was amplified in the primary and secondary transformed cells but not in the original tumor cells. Expression of the mos oncogene was very high in the primary and secondary transformants, but mos mRNA was undetectable in the original tumor cells. A genomic DNA fragment containing the activated mos oncogene was cloned and sequenced. The upstream mouse sequence of the mos oncogene, which functions as the transcription terminator, was lost and replaced by a mouse endogenous long terminal repeat (LTR) element that provides the promoter sequence, resulting in high expression of the gene. The rearrangement apparently occurred during transfection, since the polymerase chain reaction (PCR) product encompassing the junction region was present in the primary and secondary transformants but not in the original tumor cells. The LTR element is likely to have been amplified during the skin tumor development caused by UV irradiation. Southern blot hybridization showed that the copy number of LTR in the tumor cells was significantly higher than that in normal skin cells. The amplification of the LTR in the cells may have increased the chance of recombination between the LTR and c-mos gene during the DNA transfection. PMID- 8455929 TI - Role of transforming growth factor alpha (TGF-alpha) in the transformation of ras transfected rat intestinal epithelial cells. AB - Most intestinal tumors express transforming growth factor alpha (TGF-alpha) while normal immature crypt cells, the targets for tumor initiation, do not. We have used a rat intestinal cell line derived from immature epithelial crypt cells (IEC 18) to investigate the role of this growth factor in intestinal tumorigenesis. ras transformation of IEC-18 cells induces expression and secretion of TGF-alpha. By studying several independently derived IEC-ras clones, we have established that the amount of TGF-alpha secreted is proportional to the level of activated ras expressed by each clone. The growth of all ras-transformed IEC clones is significantly inhibited by neutralizing antibodies against TGF-alpha and by an antisense TGF-alpha expression vector, indicating a mitogenic role for this growth factor through an autocrine loop. To determine whether TGF-alpha itself can transform intestinal cells, IEC-18 clones transfected with TGF-alpha expression vectors were isolated and characterized. None of the TGF-alpha expressing clones show any signs of tumorigenic transformation even when they secrete as much TGF-alpha as the IEC-ras clones. It seems, therefore, that TGF alpha per se does not have the capacity to transform rat epithelial intestinal cells and that its role is mostly related to autocrine growth stimulation. PMID- 8455930 TI - Characterization of a third ras gene, rasB, that is expressed throughout the growth and development of Dictyostelium discoideum. AB - Previous reports have indicated that the cellular slime mold Dictyostelium discoideum possesses two ras genes (rasG and rasD) and one rap gene (rap1). All three genes are developmentally regulated, with each showing a different pattern of transcription during the Dictyostelium life cycle. To establish whether there are additional ras or rap genes in Dictyostelium, we used degenerate oligonucleotide primers to the highly conserved GTP-binding domains and both ras- and rap-unique sequences to amplify products from cDNA using the polymerase chain reaction (PCR). No additional rap genes were amplified, but a fragment whose nucleotide sequence predicted a novel ras gene was isolated. Using this PCR product as a probe, a full-length cDNA clone was isolated and sequenced. Its deduced amino acid sequence predicted a 197 amino acid protein that is 71% and 68% identical to RasG and RasD respectively. The new ras gene contains the conserved Ras-specific effector domain, the conserved binding site for the Ras specific Y13-259 monoclonal antibody, and shows greater sequence similarity to the human H-Ras protein than to any other mammalian Ras protein. In view of this high level of identity to the ras gene subfamily, we have designated this gene rasB. Northern blot analysis has shown that rasB is developmentally regulated with maximum levels of a single 950-bp message detected during vegetative growth and the first 8 h of development. PMID- 8455931 TI - Cyclins D1 and D2 are differentially expressed in human B-lymphoid cell lines. AB - The cyclin D1 gene can be transcriptionally activated in lymphoid tumours as a result of chromosomal rearrangements but is normally silent in B and T lymphocytes. By isolating cyclin D1-related cDNAs from a B-lymphoid cell line, we identified clones that contain the coding sequences of human cyclin D2. The predicted 289 amino acid protein shares 63% identity with human cyclin D1. Although cyclin D2 transcripts were detected in many lymphoid cell lines, it was not ubiquitously expressed and there was no apparent correlation with cyclin D1 levels. For example, two B-cell leukaemia lines, JVM-2 and Karpas 620, both of which have 11q13 translocations and express cyclin D1, contained markedly different amounts of cyclin D2. An obvious distinction between these cells is that the JVM-2 line, which expresses high levels of cyclin D2, was immortalized by Epstein-Barr virus (EBV). We subsequently found that cyclin D2 is consistently expressed in group III Burkitt's lymphoma (BL) and in lymphoblastoid cell lines immortalized by EBV, but not in group I BLs, in which expression of the EBV genome is more restricted. The data imply that the D-type cyclins may have non overlapping functions at specific stages of lymphocyte differentiation and that the expression of cyclin D2 may be influenced, directly or indirectly, by EBV. PMID- 8455932 TI - Developmental and cell lineage specificity of raf family gene expression in mouse testis. AB - The proto-oncogene c-raf-1 and the related genes A-raf and B-raf encode serine/threonine protein kinases thought to be involved in regulating gene expression by transducing extracellular signals into the cell. All three raf family genes have been shown previously to be expressed in mouse testis. Northern and in situ hybridization analyses with probes specific for each gene demonstrated that c-raf-1 mRNA is ubiquitously expressed in both somatic and germ cells as a 3.1-kb transcript. Additionally, the levels of c-raf-1 expression are developmentally regulated in the germ cells, exhibiting highest expression in early pachytene spermatocytes and decreasing progressively through later stages. A-raf is expressed predominantly in the somatic compartment as two transcripts of 2.6 and 4.3 kb. A-raf expression in Leydig cells appears to be elevated in testes undergoing spermatogenesis. In contrast, B-raf is expressed as two major transcripts of 4.0 and 2.6 kb, with the 4.0-kb transcript first expressed at low levels in pachytene spermatocytes and the more abundant 2.6-kb transcript restricted to post-meiotic spermatids. These studies indicate that each raf gene exhibits a characteristic, limited pattern of expression and suggests that the different forms may play a unique regulatory role in androgen production and/or spermatogenesis. PMID- 8455933 TI - CpG methylation inactivates the promoter activity of the human retinoblastoma tumor-suppressor gene. AB - Cytosine methylation of CpG sites in the promoter region of eucaryotic genes is involved in the inactivation of expression of certain genes. Given that methylation can lead to reduced transcription, it is possible that expression of tumor-suppressor genes is also inactivated by hypermethylation, thereby contributing to the etiology of cancer. Recently we found five sporadic retinoblastoma tumors (16% of all unilateral cases) with hypermethylation of the 5' end of the retinoblastoma gene without detecting any structural abnormalities. However, it is unclear whether the promoter of the retinoblastoma gene is actually inactivated by its hypermethylation. Here we show that specific hypermethylation in the promoter region of the retinoblastoma gene reduces its expression to only 8% of the unmethylated control. Furthermore, we have found that two transcription factors important for the promoter activity, an activating transcription factor (ATF)-like factor and the retinoblastoma binding factor 1, do not bind when their recognition sequences are CpG methylated. These results in vitro strongly support the hypothesis that CpG methylation of the human tumor suppressor gene can result in the inactivation of the gene and thus lead to oncogenesis. PMID- 8455934 TI - p53 confers a selective advantage on transfected HeLa cells. AB - The p53 gene, which is frequently mutated in various tumors, encodes a phosphoprotein thought to have a key role in the regulation of cell proliferation. To explore their biological effects, the HeLa carcinoma line, which does not express p53, was co-transfected with plasmid constructs expressing wild-type or mutant p53 proteins, or unrelated proteins, along with a plasmid conferring resistance to a neomycin-kanamycin antibiotic analog (G418). Both wild type and mutant forms of p53 stimulated the number of G418-resistant colonies between 5- and 36-fold. Further investigation of colony development revealed that p53 enhanced cell survival, leading to increased colony numbers, but did not stimulate cell growth. Nonetheless, we suggest that an initial slowing of cell growth caused by expression of the unintegrated p53 plasmids renders the transfectants resistant to selection with G418, thus causing a higher frequency of G418-resistant colonies. p53 constructs were found to be expressed transiently in HeLa cells as expected, but the G418-resistant colonies frequently failed to express p53. This loss of p53 expression may be due to negative regulatory effects of p53 on the cytomegalovirus promoter that drives the selection marker. PMID- 8455935 TI - Effect of bcl-2 proto-oncogene expression on cellular sensitivity to tumor necrosis factor-mediated cytotoxicity. AB - Introduction and expression of the proto-oncogene bcl-2 (B-cell lymphoma/leukemia 2) has been shown to extend the survival of certain hematopoietic cell lines after growth factor deprivation, by blocking apoptosis or programmed cell death. We investigated the effect of bcl-2 expression on cellular sensitivity to lysis by tumor necrosis factor (TNF), a cytokine capable of inducing apoptosis in several tumor cell lines. Introduction of the human bcl-2 gene in the highly TNF sensitive L929 mouse fibrosarcoma cell line did not result in altered TNF sensitivity. Likewise, NIH3T3 and REF cells, which are resistant to TNF cytotoxicity but become TNF sensitive upon cotreatment with actinomycin D or upon expression of the adenovirus E1A gene, did not show altered TNF sensitivity upon bcl-2 transfection. Despite constitutive expression of the endogenous bcl-2 gene, human MCF7 breast carcinoma cells, as well as HL60 promyelocytic leukemia and U937 histiocytic lymphoma cell lines were found to be TNF sensitive. bcl-2 overexpressing derivatives of these cell lines did not acquire reduced TNF sensitivity and still exhibited the characteristic pattern of internucleosomal DNA fragmentation of TNF-induced apoptosis. Moreover, bcl-2 expression in the interleukin 3 (IL-3)-dependent myeloid cell line 32D protected these cells from apoptosis resulting from growth factor deprivation, but not from apoptosis induced by TNF. These data clearly establish the absence of a correlation between bcl-2 gene expression and cellular sensitivity to TNF-induced cell lysis. These findings are discussed in the context of the hypothesis of different pathways for induction of apoptosis, only some of which are affected by bcl-2 expression. PMID- 8455936 TI - cDNA cloning of mouse ret proto-oncogene and its sequence similarity to the cadherin superfamily. AB - We report the nucleotide sequence of the mouse ret proto-oncogene (proto-ret) and the deduced amino acid sequence. It encodes a transmembrane tyrosine kinase of 1115 amino acids that shows 83% homology with the human proto-Ret protein. The amino acid sequence revealed that the structures of the extracellular domain as well as the tyrosine kinase domain are similar in human and mouse proto-Ret proteins. Interestingly, the extracellular domains of both human and mouse proto Ret proteins contain a cadherin-related sequence that is known to be important for Ca(2+)-dependent homophilic binding of the cadherins. When we examined transcription of the proto-ret gene in a variety of mouse tissues, it was detected in lymph nodes of C3H/HeJ-gld/gld mice and in normal mouse spinal cord. Furthermore, its transcription was found in the Neuro-2a mouse neuroblastoma cell line but not in 13 other rodent cell lines surveyed. Western blot analysis showed that proto-Ret proteins are expressed as 140-kDa and 160-kDa glycoproteins in Neuro-2a cells. PMID- 8455937 TI - DNA binding by N- and L-Myc proteins. AB - N- and L-Myc, like c-Myc, contain adjacent basic region (BR), helix-loop-helix (HLH) and leucine zipper (LZ) motifs, which characterize a family of DNA-binding proteins. We have used a polymerase chain reaction (PCR)-based binding site selection technique to demonstrate that the most highly preferred binding site for both N- and L-Myc fusion proteins contains a CACGTG motif, the core binding sequence previously identified for c-Myc. Further analysis identified other N-Myc binding sequences, including asymmetric sequences such as CAT-GTG. N-Myc, like c Myc, preferentially forms heterodimeric DNA-binding complexes with Max protein. Mutational analyses of N-Myc basic region (BR), helix-loop-helix (HLH) and leucine zipper (LZ) regions revealed that all three regions are necessary for DNA binding by N-Myc-Max complexes, and that dimerization requires both HLH and LZ motifs, while BR sequences are needed only for DNA binding. Our findings support the notion that the LZ motif is a critical element in dimer formation by bHLH-LZ proteins. PMID- 8455938 TI - Early down-regulation of c-myc in dimethylsulfoxide-induced mouse erythroleukemia (MEL) cells is mediated at the P1/P2 promoters. AB - A block of RNA elongation in exon 1 of the murine c-myc gene has been described for normal mouse fibroblasts, lymphoid and myeloid cell lines and mouse erythroleukemia (MEL) cells. MEL cells differentiate after induction with the chemical agent dimethylsulfoxide (DMSO). The rapid initial down-regulation of c myc that occurs after treatment with DMSO has been explained by an increase in the block of RNA elongation within the 3' part of c-myc exon 1. In contrast to these reports, we find that down-regulation of c-myc in DMSO-induced MEL cells occurs at the c-myc P1 and P2 promoters. The P1 promoter is repressed by inhibition of initiation, whereas transcription of P2 RNA is blocked by retention of RNA polymerase II at or close to the P2 promoter. The earlier described block of RNA elongation at a run of five thymidines in the 3' part of c-myc exon 1 was not observed. PMID- 8455939 TI - An Eph-related receptor protein tyrosine kinase gene segmentally expressed in the developing mouse hindbrain. PMID- 8455940 TI - A novel Yes-related kinase, Yrk, is expressed at elevated levels in neural and hematopoietic tissues. AB - While screening a chicken kidney cDNA library for the normal homolog of the yes oncogene, we isolated a clone that encodes a novel non-receptor type protein tyrosine kinase of the Src family. We named this gene product Yrk (York), as an acronym for Yes-related kinase. As predicted from the cDNA sequence, the Yrk protein consists of 536 amino acids and has all the canonical features of a Src kinase. At the amino terminus it contains a myristylation signal, followed by a unique domain, SH3 and SH2 motifs, an ATP binding site, a kinase region and a carboxy-terminal sequence with a potential regulatory tyrosine at position 530. The sequence of the Yrk protein showed 79% identity with human Fyn and 72% identity with chicken Yes. To eliminate the possibility that the Yrk protein is an avian homolog of mammalian Fyn, we isolated and sequenced the chicken fyn cDNA. The sequence data together with Southern and Northern blot analyses showed that the chicken yrk gene is distinct from the chicken fyn gene. Antibodies generated against the unique domain of the yrk protein expressed in bacteria precipitated a 60-kDa protein that was active in an immune complex kinase assay and was phosphorylated on tyrosine. Expression of the Yrk protein in adult chicken tissues was elevated in cerebellum and spleen. Relatively high levels of Yrk were also found in lung and skin. PMID- 8455941 TI - The transcriptionally active factors mediating the effect of the HTLV-I Tax transactivator on the IL-2R alpha kappa B enhancer include the product of the c rel proto-oncogene. AB - The transactivator HTLV-I Tax activates the promoter of the gene coding for the interleukin 2 alpha-chain receptor (IL-2R alpha) via a kappa B site that can bind several protein species of the rel family. Tax1 strongly activates the enhancer activity of this motif, in both epithelial HeLa and lymphoid Jurkat cells. This activation was not observed in undifferentiated embryocarcinoma F9 cells. Overexpression of the p50, p65 and Rel proteins in these cells showed that significant activation of the IL-2R alpha kappa B site was observed only with Rel and Rel plus p65. Moreover, whereas both Tax and phorbol 12-myristate 13-acetate (PMA) are able to efficiently induce the binding of NF-kappa B to the IL-2R alpha kappa B site, PMA is functionally inactive. Using the DNA affinity precipitation assay, we observed that Tax1 is able to efficiently induce the binding of Rel, whereas PMA is not. This established a clear difference between both stimuli, indicating that Rel is the functionally active factor. We conclude from these results that the functional activity of members of the rel family is regulated by their interaction with DNA and that Rel can be a potent transcriptional activator on specific kappa B sites. PMID- 8455942 TI - Suppression of oncogene-induced transformation by a deletion mutant of c-jun. AB - Jun and Fos proteins are DNA-binding proteins that are involved in the control of gene expression through transcriptional regulation. We have made a deletion mutant of the c-jun gene that lacks amino acids 3-122 of c-jun, and thus is missing the major transactivation domain of c-jun, but retains the DNA-binding and leucine zipper domains. Unlike c-Jun, the mutant protein is unable to stimulate the transcription of an AP-1 responsive gene, and unlike c-jun this mutant gene is unable to transform rat embryo cells in cooperation with an activated ras gene. However, this mutant protein blocks in vitro DNA binding of Jun-Jun homodimers and Jun-Fos heterodimers, transcriptional activation induced by c-jun or c-fos and transformation of rat embryo cells induced by an activated ras gene and a deregulated c-jun or c-fos gene. In addition, transformation of rat embryo cells induced by an activated ras gene in the presence of the tumor promoter 12-O-tetradecanoyl phorbol 13-acetate (TPA) or by ras plus SV40 large T antigen is also inhibited by this dominant-negative mutant, suggesting that a member of the jun or fos family is involved in the pathways leading to transformation in these systems as well. The possible molecular mechanisms by which this dominant-negative mutant of c-jun blocks the functions of wild-type jun and fos family members are discussed. PMID- 8455943 TI - Human papillomavirus type 16 E7 regulates E2F and contributes to mitogenic signalling. AB - We have produced human papillomavirus type 16 E7 protein in a bacterial expression system and examined the mitogenic activity of this protein in Swiss 3T3 cells after scrape loading. The ability of E7 to induce cellular DNA synthesis in quiescent mouse fibroblasts is strongly enhanced by the presence of a single growth factor such as insulin. Although only weakly mitogenic, introduction of E7 alone resulted in the rapid induction of the transcriptionally active form of E2F, which was not enhanced further by the addition of insulin. Mutant E7 proteins defective for RB binding failed to induce the active form of E2F or act synergistically with insulin to stimulate DNA synthesis. The ability of E7 to regulate E2F may therefore be necessary, but is not sufficient, for full induction of DNA synthesis. PMID- 8455944 TI - A cell culture model system for genetic analyses of the cell cycle by targeted homologous recombination. AB - Analysis of how external proliferation signals impinge on the regulation of the cell cycle is ideally performed in cells that are capable of normal physiological withdrawal into the quiescent (G0) phase of the cell cycle as well as resumption of growth following appropriate stimuli. Targeted homologous recombination (gene targeting) provides an important new approach to determine the function of specific genes in these cellular processes. Current gene targeting methodology necessitates the use of immortal and stably diploid cell lines. This report investigates several rodent cell lines, by both genetic and physiological criteria, for use in gene targeting studies of the G0 to G1 transition. All murine cell lines examined were aneuploid. Some rat cell lines were euploid by chromosome number, but three specific genes, c-myc, c-raf-1 and Rb, were not always diploid. Only one cell line, an early-passage subclone of the Rat-1 cell line, was diploid for c-myc, c-raf-1 and Rb. An hprt- derivative of this cell line was isolated (designated TGR-1) and its karyotype was established by G banding. TGR-1 cells were shown to withdraw into G0 upon serum starvation and to uniformly enter S phase after refeeding. Expression patterns of the c-myc, c-raf 1 and Rb genes and several properties of the gene products were found to be normal. The frequency of targeted homologous recombination of the c-myc and c-raf 1 loci was found to be within values observed with other cell lines. Thus, by both genetic and physiological criteria the TGR-1 cell line is a good model system for the analysis of the roles of c-myc, c-raf-1 and Rb in signal transduction, and will probably prove useful in studies involving other genes. PMID- 8455945 TI - Melittin-induced hyperactivation of phospholipase A2 activity and calcium influx in ras-transformed cells. AB - The activated ras oncogene is a key mediator of cellular transformation and is present in a wide variety of primary human neoplasms. The biochemical role of the ras oncogene in cellular transformation is at present unclear, and hence approaches to control its activities in transformed cells have met with limited success. Previous studies have demonstrated the ability of melittin, a 26 amino acid amphipathic peptide from bee venom, to specifically counterselect for cells in culture that express high levels of the ras oncogene product. The biochemical basis for this counterselection is currently unknown. This study demonstrates the ability of melittin to hyperactivate phospholipase A2 (PLA2) in ras-transformed cells by the mediation of enhanced influx of calcium ions (Ca2+). This hyperactivation of PLA2 and Ca2+ mobilization in ras-transformed cells by melittin is mimicked by the calcium ionophore, A23187. Both melittin- and A23187 mediated PLA2 hyperactivation require Ca2+. However, the action of melittin is strongly dependent on extracellular Ca2+, whereas that of A23187 is not. Melittin induced Ca2+ influx and PLA2 hyperactivation is inhibited by manganese ions (Mn2+). These studies reveal a close correlation between the extent of PLA2 hyperactivation and Ca2+ mobilization, suggesting a causal relationship. PMID- 8455946 TI - Alternative splicing of the RBP1 gene clusters in an internal exon that encodes potential phosphorylation sites. AB - We have isolated cDNA and genomic clones for the human retinoblastoma binding protein 1 (RBP1) gene, and have identified alternative splicing of RBP1 clustered within a 207-nucleotide internal exon. Three of the predicted RPB1 peptides share amino-terminal and carboxy-terminal domains, while a fourth species encodes a distinct carboxy-terminal domain. Functional analysis of these peptides demonstrated that they are capable of precipitating retinoblastoma (RB) protein in vitro from K562 cell lysates, but cannot bind to mutant RB protein. However, each of the RBP1 peptides differed within an internal exon that contains potential casein kinase II and p34cdc2 phosphorylation sites. Immunoblot analysis using polyclonal alpha-RBP1 antiserum revealed that the RBP1 protein is expressed in a wide range of cell lines of differing histologic type and migrates on sodium dodecyl sulfate-polyacrylamide gel electrophoresis predominantly as a 200-kDa protein. Immunohistochemical analysis using the alpha-RBP1 antiserum demonstrated a distinct nuclear staining pattern that was eliminated when the antiserum was preabsorbed with RBP1 peptide. The RBP1 gene encodes a widely expressed 200-kDa nuclear protein and undergoes alternative splicing that predicts a family of RB binding peptides. PMID- 8455947 TI - Potential value of increased MYC but not ERBB2 RNA levels as a marker of high risk mastopathies. AB - MYC and ERBB2 levels were measured in 38 benign breast diseases using a semiquantitative in situ hybridization technique. Mean levels of MYC and ERBB2 gene expression in benign tissues were similar to those measured in 15 breast cancers with no amplification at the loci concerned. Interestingly, MYC but not ERBB2 RNA levels were increased (t-test, P = 0.03) in benign mastopathies of patients with a first-degree (mother/sister) family history (FH) of breast cancer. Among patients without a first-degree FH, MYC RNA levels were significantly higher (t-test, P = 0.02) during the follicular (preovulatory) than the luteal (post-ovulatory) phase and also significantly higher than levels observed in patients with no menstrual cycle (peri- or postmenopausal) (P = 0.004), indicating an in vivo hormonal regulation of MYC. After exclusion of the first-degree FH patients a higher MYC expression was detected in atypia than in other histological types at the follicular but not at the luteal phase, suggesting an increased sensitivity of these high-risk lesions to estrogens. We propose that in addition to a family history and proliferative atypia, elevated MYC RNA levels during the post-ovulatory phase could potentially be used as a marker of the risk of developing breast cancer. The increase in MYC RNA in high risk breast diseases also suggests that MYC deregulation might be involved in the early stages of mammary carcinogenesis. PMID- 8455948 TI - Characterization of a functional promoter for the human thyroid hormone receptor alpha (c-erbA-1) gene. AB - The thyroid hormone receptor alpha (THRA or c-erbA-1) gene belongs to a family of genes that encode nuclear receptors for various hydrophobic ligands such as steroids, retinoic acid and thyroid hormones. We have previously described the genomic organization of the human THRA gene, which comprises 10 exons distributed along 27 kbp of genomic DNA. We describe here a promoter that initiates THRA transcription. This promoter contains no obvious TATA-like element but is very GC rich and harbors numerous Sp1 sites. It also contains several sites similar to previously described cis-acting sequences including hormone-responsive elements (HREs). When transfected into cultured HeLa cells, it drives the expression of a CAT reporter gene. The activity of this human THRA promoter is enhanced by the synthetic glucocorticoid dexamethasone but seems unaffected by thyroid hormones. PMID- 8455949 TI - Expression of AML1-ETO fusion transcripts and detection of minimal residual disease in t(8;21)-positive acute myeloid leukemia. AB - The t(8;21) translocation breakpoint, which is observed in acute myeloid leukemia (AML), has recently been cloned and a fusion transcript identified. We have now designed primer sets capable of amplifying the breakpoint junction of the fusion transcript by the reverse transcription-polymerase chain reaction (RT-PCR). Primer set 821U/821D1 amplified a 200-bp DNA fragment, and primer set 821U/821D2 amplified a 1.2-kb DNA fragment in all t(8;21)-positive AML tested. Sequence analysis of the amplified DNA fragments demonstrated that all fusion transcripts were fused at exactly the same site, indicating that this translocation breakpoint occurs within a single intron of the AML1 and ETO genes. Forty-five cycles of RT-PCR were used to detect residual t(8;21)-positive leukemia cells in three patients who had been in complete remission for 1, 3 and 5 years. Minimal residual disease was found in all three samples. Northern blot analysis demonstrated that two fusion transcripts of 7 and 10 kb were expressed in the t(8;21)-positive AML and that the ETO gene is not normally expressed in the hematopoietic system. Expression of a normal 5.5-kb ETO mRNA was found in the lung. From these results we concluded that expression of the ETO gene in t(8;21) positive AML was activated as a result of the translocation. PMID- 8455950 TI - Requirement of an ETS-binding element for transcription of the human lck type I promoter. AB - The requirement for cis-acting DNA sequences for transcriptional activity of the human lck type I promoter was investigated in two human cell lines that express type I transcripts, the leukemic T-cell line, Jurkat, and the colon carcinoma line, SW620. Transient transfection assays in Jurkat and SW620 cells revealed negative and positive cis-acting regulatory elements in the lck type I promoter between -570 and -480 and between -128 and -63 respectively. For the latter, a triple point mutation of a sequence, GCAGGAAGT, from -99 and -91 resulted in complete loss of lck type I promoter activity in both Jurkat and SW620 cells. In vitro binding assays indicated that this sequence, denoted the ETS-binding element or EBE, can interact with the lymphoid-specific transcription factor ETS 1. Thus, a protein(s) in the ETS family appears to be required for transcription of the lck type I promoter in T cells and may be important for the activation of the lck gene in human colon carcinoma. PMID- 8455952 TI - Behavioral risk factors. PMID- 8455951 TI - Induction of the metastatic phenotype by transfection of a benign rat mammary epithelial cell line with the gene for p9Ka, a rat calcium-binding protein, but not with the oncogene EJ-ras-1. AB - The rat mammary epithelial cell line, Rama 37, yields benign, non-metastasizing adenomatous tumours in syngeneic Wistar-Furth rats. Transfection of this line with a drug resistance plasmid containing both the gene for resistance to Geneticin (neo) and the gene for p9Ka (pSV2neo-p9Ka), a rat calcium-binding protein, or with a similar plasmid containing neo and the oncogene EJ-ras-1 (pSV2neo-ras) yields drug-resistant transformants that express high levels of the p9Ka or EJ-ras-1 mRNAs and proteins. These transfected cells all produce tumours when injected at subcutaneous sites with a shorter median latent period than the tumours produced by the parental untransfected Rama 37 cells in syngeneic hosts. Cells transfected with pSV2neo-p9Ka yield a higher incidence of tumours than untransfected Rama 37 cells, many of which metastasize to lungs and/or lymph nodes in syngeneic rats. However, cells transfected with pSV2-neo-ras or pSV2neo plasmid alone yield tumours that fail to metastasize. Immunofluorescent studies suggest an association of p9Ka with the cytoskeleton, as depicted by F-actin staining with the reagent phalloidin. It is suggested that the transfection of copies of the gene for the rat calcium-binding protein p9Ka can enhance the tumorigenic potential and induce the metastatic phenotype in this rat mammary model, whereas transfection of control plasmid DNA or the oncogene EJ-ras-1 fails to induce the metastatic phenotype, although EJ-ras-1 transfectants, like those containing p9Ka, possess increased growth properties in vivo. PMID- 8455953 TI - Delegation of medication. PMID- 8455954 TI - Shock and disbelief: supporting parents who experience the sudden death of their child. PMID- 8455955 TI - Coping with traffic tickets. PMID- 8455956 TI - Celebrate leadership 1903-1993. PMID- 8455957 TI - Pennsylvania nurses address child care needs. PMID- 8455958 TI - National transplantation pregnancy registry established. PMID- 8455959 TI - Supervisor suspects staff nurse to have alcohol problem. PMID- 8455960 TI - Nitric oxide (NO) and nociceptive processing in the spinal cord. AB - There is considerable evidence to implicate N-methyl-D-aspartate (NMDA) receptor activation in the mechanisms that underly thermal hyperalgesia in the spinal cord. As many of the effects of NMDA receptor activation appear to be ultimately mediated through production of nitric oxide (NO), recent reports have begun to define the role of NO in spinal nociceptive processing. From this evidence, it is likely that NO, produced in neurons in the spinal cord that contain NO synthase, like NMDA, plays a pivotal role in multisynaptic local circuit nociceptive processing in the spinal cord. Collectively, these reports suggest that the reflex withdrawal response to noxious heat is not mediated through activation of NMDA receptors and subsequent production of NO and cGMP, but that the acute NMDA produced facilitation of thermal reflexes is NMDA-, NO- and cGMP-mediated and that a sustained production of NO and subsequent activation of soluble guanylate cyclase (GC-S) in the lumbar spinal cord appears to be required for maintenance of the thermal hyperalgesia produced in persistent pain models. As our knowledge and understanding of the new and intriguing class of neurotransmitters typified by NO emerges, it is likely that the next few years of pain and analgesia research will focus on the cellular events underlying mechanisms of chronic pain. PMID- 8455961 TI - Methadone in the management of cancer pain: a review. AB - Methadone is a synthetic opiate receptor agonist that has been available for more than 40 years. Although its main use has been in the maintenance treatment of opioid addicts, it has excellent analgesic effects and low cost. Its use is limited by its long and unpredictable half-life and by the limited knowledge of the most appropriate method for titration and interval of administration. Most reports on this drug are uncontrolled and limited to a small number of patients receiving low doses of methadone. Methadone should be titrated carefully and individualized doses and intervals should be determined for each patient. Future research should attempt to determine the equi-analgesic dose for chronic use, its effectiveness and tolerance when used in high doses, and its absorption and tolerance using alternative routes, e.g., rectal and subcutaneous. PMID- 8455962 TI - Intra-articular ultrasonic stimulation and intracutaneous electrical stimulation: evoked potential and visual analogue scale data. AB - The reproducibility of focussed ultrasound-induced intra-articular pain was compared with that of electrically induced cutaneous pain over a period of time by measuring both the evoked potential (EP) amplitude and visual analogue scale (VAS) score. The responses to ultrasound were more variable than those to electrical stimulation. A greater degree of accommodation occurred during electrical stimulation compared with ultrasound stimulation. A statistically significant correlation between the EP amplitude and the VAS score was found for each form of stimulation. Changes in EP amplitude correlated with changes in the perception of pain as measured by the VAS score, rather than stimulus intensity, which remained constant for each subject throughout the duration of the experiment. A single oral dose of pethidine produced a statistically significant decrease in the EP amplitude and the VAS score in each case. PMID- 8455963 TI - A Fear-Avoidance Beliefs Questionnaire (FABQ) and the role of fear-avoidance beliefs in chronic low back pain and disability. AB - Pilot studies and a literature review suggested that fear-avoidance beliefs about physical activity and work might form specific cognitions intervening between low back pain and disability. A Fear-Avoidance Beliefs Questionnaire (FABQ) was developed, based on theories of fear and avoidance behaviour and focussed specifically on patients' beliefs about how physical activity and work affected their low back pain. Test-retest reproducibility in 26 patients was high. Principal-components analysis of the questionnaire in 210 patients identified 2 factors: fear-avoidance beliefs about work and fear-avoidance beliefs about physical activity with internal consistency (alpha) of 0.88 and 0.77 and accounting for 43.7% and 16.5% of the total variance, respectively. Regression analysis in 184 patients showed that fear-avoidance beliefs about work accounted for 23% of the variance of disability in activities of daily living and 26% of the variance of work loss, even after allowing for severity of pain; fear avoidance beliefs about physical activity explained an additional 9% of the variance of disability. These results confirm the importance of fear-avoidance beliefs and demonstrate that specific fear-avoidance beliefs about work are strongly related to work loss due to low back pain. These findings are incorporated into a biopsychosocial model of the cognitive, affective and behavioural influences in low back pain and disability. It is recommended that fear-avoidance beliefs should be considered in the medical management of low back pain and disability. PMID- 8455964 TI - Efficacy of cognitive therapy for chronic low back pain. AB - The effects of outpatient group cognitive therapy, relaxation training, and cognitive therapy in combination with relaxation training on chronic low back pain and associated physical and psychosocial disability were evaluated and compared. One-hundred and two mildly disabled chronic low back pain patients were assigned randomly to a waiting-list (WL) control condition and the 3 treatments. Patient self-report and observational measures were obtained pretreatment and post-treatment for all conditions, and at 6- and 12-month follow-ups for the treatment conditions. Pain intensity decreased significantly pre- to post treatment for patients in all 3 treatment conditions, but not the WL condition. Depressive symptoms and disability improved significantly in all conditions (including the waiting list) from pretreatment to post-treatment, with no statistically significant differences among treatments. At both follow-ups, all 3 treatment groups remained significantly improved from pretreatment, with no statistically significant differences between treatments. PMID- 8455965 TI - CSF and plasma concentrations of morphine and morphine glucuronides in cancer patients receiving epidural morphine. AB - Thirty-five cancer patients, treated with chronic epidural morphine, were assayed for plasma and cerebrospinal fluid (CSF) minimum steady-state concentrations (Css min) of morphine (M), morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) by high performance liquid chromatography (HPLC). A linear dose concentration relationship was found for the 3 substances in plasma and for morphine and M3G in CSF. The mean +/- S.E.M. CSF/plasma morphine ratio was 158 +/ 43. In CSF, the concentrations of morphine exceeded those of the metabolites substantially and, normalized to morphine, the mean CSF M/M3G/M6G ratio was 1:0.05:0.02. In plasma, the metabolite concentrations were higher than the parent drug and the plasma M/M3G/M6G ratio was 1:12:3. The mean M3G and M6G concentrations in CSF were 40-60% of those found in plasma. Indication of cerebral formation of M3G was found in 1 patient. Pain relief, evaluated by a visual analogue scale (VAS), did not correlate with the CSF M3G concentrations or with the M3G/M ratio. CSF M6G concentrations were low and did not contribute to any detectable analgesia. We conclude that after epidural administration of morphine, the M3G and M6G metabolites in CSF are low compared to unchanged morphine and seem to have little influence on analgesia. However, the fact that a significant passage of the glucuronide metabolites occurs to the CSF may indicate a role in morphine analgesia after other routes of administration. PMID- 8455966 TI - Celiac plexus block versus analgesics in pancreatic cancer pain. AB - Twenty pancreatic cancer patients were studied to assess the effectiveness and duration of celiac plexus block compared to traditional treatment with analgesics by considering the previous and subsequent consumption of narcotics until their death. After 1 week of therapy with NSAID-narcotic sequence according to the WHO method, 10 patients were continued on this treatment, while the other 10 patients underwent celiac plexus block. Subsequently analgesics were administered as in the patients not treated by the block. A visual analogue score and opioid consumption were used to calculate the effective analgesic dose at weekly intervals until death. Celiac plexus block made pain control possible with a reduction in opioid consumption for a mean survival period of about 51 days. Administration of only analgesics resulted in an equal reduction in VAS pain score until death, but with more unpleasant side effects than when using celiac plexus block. PMID- 8455967 TI - Muscle tenderness and pressure pain thresholds in headache. A population study. AB - Tenderness and pain thresholds in pericranial muscles were studied in a random sample of 735 adults aged 25-64 years. This study was a part of a multifaceted, epidemiological study of different headache disorders. Manual palpation and pressure pain threshold were performed by observers blinded to the persons' history of headache. The aim of the study was to evaluate the possible role of pericranial myofascial nociception in headache pathogenesis. Tenderness in migraineurs did not differ from non-migraineurs. Subjects with episodic tension type headache and females with chronic tension-type headache were more tender than the rest of the population, and males without any experience of headache were less tender than the rest of the male population. A strong positive correlation between tenderness and frequency of tension-type headache was found (males: P < 10(-4); females: P < 10(-5)), while no relation between tenderness and migraine frequency was seen (P = 0.43). In subjects having actual headache at the day of examination tenderness was 32% increased compared to a matched group with identical usual frequency of headache, but without headache during the examination. A significant relation of tenderness to the recency of last episode of headache was detected in both sexes after control for usual frequency and actual headache (males: P < 10(-3); females: P < 10(-4)). Pressure pain thresholds were largely normal indicating normal pain processing and contradicting the idea that tension-type headache mainly is due to generally increased pain sensitivity. This study supports the pathogenetic importance of muscular factors in tension-type headache, while muscular factors are of no primary importance in migraine. PMID- 8455968 TI - Developmental changes in pain expression in premature, full-term, two- and four month-old infants. AB - The purpose of this study was to examine the behavioural responses of infants to pain stimuli across different developmental ages. Eighty infants were included in this cross-sectional design. Four subsamples of 20 infants each included: (1) premature infants between 32 and 34 weeks gestational age undergoing heel-stick procedure; (2) full-term infants receiving intramuscular vitamin K injection; (3) 2-month-old infants receiving subcutaneous injection for immunisation against DPT; and (4) 4-month-old infants receiving subcutaneous injection for immunisation against DPT. Audio and video recordings were made for 15 sec from stimulus. Cry analysis was conducted on the first full expiratory cry by FFT with time and frequency measures. Facial action was coded using the Neonatal Facial Action Coding System (NFCS). Results from multivariate analysis showed that premature infants were different from older infants, that full-term newborns were different from others, but that 2- and 4-month-olds were similar. The specific variables contributing to the significance were higher pitched cries and more horizontal mouth stretch in the premature group and more taut tongue in the full term newborns. The results imply that the premature infant has the basis for communicating pain via facial actions but that these are not well developed. The full-term newborn is better equipped to interact with his caretakers and express his distress through specific facial actions. The cries of the premature infant, however, have more of the characteristics that are arousing to the listener which serve to alert the caregiver of the state of distress from pain. PMID- 8455969 TI - TENS for children's procedural pain. AB - A 3 x 6 factorial design with a double blind and placebo control was employed to investigate the effect of TENS treatment on pain produced by venipuncture. The three treatment groups consisted of TENS, placebo-TENS and control. Subjects were blocked into six 2-year age groups (ages: 5-17 years). During the period of the study, 896 children attending the outpatient laboratory of a general hospital were screened and 514 children completed the study. The data which were collected before venipuncture included expected pain and state anxiety. Following venipuncture, pain intensity was measured with a vertical visual analogue scale (VAS) and pain affect was assessed with McGrath's faces scale. Significant main effects for treatment and age groups were obtained. Pain intensity and affect were lowest for the TENS group and highest for the control group. The pain scores were greatest for lower age groups and lowest for higher age groups. The results of this study support the use of TENS for children's pain and the need for interventions for children's procedural pain. PMID- 8455970 TI - Hyperbaric oxygen therapy in cluster headache. AB - Preliminary reports have shown that hyperbaric oxygen (HBO) interrupts cluster headache (CH) attacks. In the present study, 6 of 7 patients with episodic cluster headache who were treated with hyperbaric oxygen experienced an interruption of the attack. In 3 of 6 responders the florid period of the cluster headache was interrupted. The other 3 patients remained without pain attacks for a period lasting from 3 to 6 days. In 6 different patients, a placebo treatment had no effect. The present findings clearly indicate that hyperbaric oxygen has not only a symptomatic effect on a single attack of cluster headache, but it also could prevent the occurrence of subsequent attacks. PMID- 8455971 TI - Meta-analysis of antidepressant-induced analgesia in chronic pain: comment. PMID- 8455972 TI - Comments on Sullivan et al., PAIN, 50 (1992) 5-13. PMID- 8455973 TI - [Rapid development in Scandinavian emergency care]. PMID- 8455974 TI - [The Anders Jahre Prize for young researchers 1992. HIV/AIDS--an epidemiological challenge]. AB - Mads Melbye was awarded the Anders Jahre prize for young scientists in 1992 for his research into epidemiological infections. His pioneering work, which has elucidated the manner in which HIV and AIDS are transmitted sexually and via contaminated blood, has been of fundamental importance in understanding AIDS as an infectious disease. The article describes how this knowledge was obtained, and how it has added to our understanding of the pathogenesis of other diseases--here exemplified by a type of cancer. PMID- 8455975 TI - [Development of ambulance services in Norway--from transportation to medical activities]. AB - In the course of 100 years ambulance services in Norway have developed from purely transport facilities to mobile medical units. The first ambulance manned by doctors appeared in 1967, and since 1974 a two-year course of training has been available to ambulance personnel. However, as the ambulance services are run on a regional basis, and as official approval of ambulance personnel as paramedical staff is still lacking, there are manifest regional differences in the quality of the services. PMID- 8455976 TI - [Emergency medical service in Finland]. AB - The article consists in a review of the development of prehospital care in Finland and of emergency medical services in Helsinki. Based on 20 years' accumulated experience at a physician staffed prehospital emergency care unit in Helsinki, emergency medical services throughout the country have begun implementing the various links in the 'chain of survival' concept. PMID- 8455977 TI - [Double emergency medical service system in Goteborg]. AB - During 1989-1991, the mobile coronary care unit (MCCU) in Gothenburg answered 10,908 calls. The most frequent cause of alarm calls was chest pain (21 per cent), whereas cardiac arrest accounted for 9 and surgical cases for 15 per cent. Severe pain was most frequent among patients with chest or abdominal pain. Despite the high frequency of chest pain, only a third of the myocardial infarction cases were attended by the MCCU. Of all cases of out-of-hospital cardiac arrest where resuscitation was attempted, 26 per cent were alive at admission to hospital, and 10 per cent at discharge, as compared with 48 and 22 per cent, respectively, among the subgroup with bystander-witnessed cardiac arrest and ventricular fibrillation as an initial finding. PMID- 8455978 TI - [Prehospital service in Denmark]. AB - In Denmark, emergency ambulances are dispatched by 41 centres manned either by trained firemen (in Copenhagen) or policemen (outside Copenhagen). In 1990, emergency ambulance calls totalled 284,000. Utilisation of emergency ambulance services increases with urbanisation. A doctor-manned ambulance is in operation in Copenhagen, and in some other large towns anaesthesiology and intensive care teams can be dispatched from hospital to give on-the-spot care. In less populated areas, some general practitioners give advanced life-support. Although many areas are serviced by ambulances equipped with defibrillators, the majority of patients receive only basic life-support from ambulance personnel. New initiatives resulting from a recent report by a commission appointed by central authorities, and focused on prehospital treatment, are expected to improve the service by raising the level of training given to ambulance personnel. PMID- 8455979 TI - Acute emergency service in Reykjavik. AB - The cardiac arrest survival rate has improved since the emergency ambulance service manned by specially trained paramedical personnel and doctors was introduced in Iceland. As the response time has been reduced, specific resuscitation measures can be applied sooner. PMID- 8455980 TI - [Inguinal hernia--still a surgical challenge]. AB - Although inguinal hernia surgery remains the commonest form of elective intervention, nonetheless there is no consensus as to which are the most important problems in the field. Several challenges await resolution: priorities, operative techniques and outcome, surgical skill, and rehabilitation. PMID- 8455981 TI - [Car fever--a new challenge for physicians]. PMID- 8455982 TI - [Our need of illness]. PMID- 8455983 TI - [Trondheim's new curriculum. A "New Deal" medical study]. AB - A new syllabus is to be introduced at the medical faculty at Trondheim University in the autumn term 1993. It is to take the form of an integrated studies model based on problem-oriented learning. The Trondheim syllabus is focused on environmental medicine, behavioural science and practical skills, but is also designed to provide a basis for continued work in scientific research. PMID- 8455984 TI - The development of sucking patterns and physiologic correlates in very-low-birth weight infants. AB - The purpose of this investigation was to assess the development of nutritive sucking patterns and physiologic correlates in very-low-birth-weight infants. Fifty infants with a mean gestational age of 29.5 weeks (SD = 1.8 weeks) and mean birth weight of 1466 g (SD = 322 g) generated 106 sucking records. The mean number of sucks and maximum pressure increased with increasing postconceptual age. The time required per burst decreased between 32 weeks and 36 weeks. The mean time between sucks also decreased. The mean heart rates for the three 5 minute periods ranged from 158.56 to 177.97 bpm. Mean oxygen saturation ranged from 94.36% to 97.15%. Mean systolic pressure ranged from 69.82 mm Hg to 76.85 mm Hg mean diastolic pressure from 43.63 mm Hg to 45.33 mmHg. Sucking parameter measurements can be used to distinguish an infant who is maturing and organizing appropriately for postconceptual age. PMID- 8455985 TI - Incidence and pattern of jaundice in healthy breast-fed infants during the first month of life. AB - The incidence and pattern of jaundice in 155 normal, full-term, breast-fed, white infants was examined. Infants were screened for jaundice on Days 2, 3, 5, 7, 9, 11, and 13 following birth using transcutaneous bilirubinometry (TcB). By Day 3, 49.7% of the infants were classified as jaundiced (> 10 mg/dl). Infants with low TcB indices on Days 2, 3, and 5 never developed jaundice as indicated by elevated TcB indices on Days 7, 9, 11, and 13. Hence, it may be possible to target infants at risk for severe jaundice prior to discharge. The observed rate of 10.3% for breast-milk jaundice (jaundice present at Day 13) is significantly higher than the highest reported rate of 2.4% (z = 6.43, p < .01). Furthermore, the pattern of jaundice in these infants does not appear to have two peaks, indicating that it is not possible to distinguish between exaggerated physiologic jaundice and breast-milk jaundice using TcB. PMID- 8455986 TI - The effect of regularly scheduled naps on sleep attacks and excessive daytime sleepiness associated with narcolepsy. AB - To investigate the effectiveness of "nap therapy" for improving alertness and reducing the frequency of sleep attacks, 16 narcoleptic subjects were studied before, during, and after a 1-month program of three regularly scheduled naps. The frequency and timing of sleep attacks, naps, and nocturnal sleep periods were recorded daily in sleep logs for 5 weeks. The severity of five common symptoms of narcolepsy and daytime alertness were assessed before and after the 1-month treatment period. Medications and usual nocturnal sleep habits were not changed during the study period. Mean sleep latency was increased significantly after 1 month of nap therapy. However, there were no significant changes in the frequency of sleep attacks or in the severity of other symptoms. Those subjects who reported more severe symptoms and who had taken more naps daily before the study period received the most benefit from the treatment. PMID- 8455987 TI - The current generation of research proposals: reviewers' viewpoints. PMID- 8455988 TI - Comparison of factor analysis options using the Home/Employment Orientation Scale. PMID- 8455989 TI - Re: 'Predicting AIDS patient care intentions among nursing students'. PMID- 8455990 TI - Development and testing of the Mastery of Stress Instrument. AB - The purpose of this research was to develop and test an instrument to measure mastery of stress. Mastery is defined as a human response to difficult or stressful circumstances in which a person gains competence, control, and dominion over the experience of stress. The instrument consists of four 15-item scales: Certainty, Change, Acceptance, and Growth. PMID- 8455992 TI - Predicting alcohol use in rural children: a longitudinal study. AB - The purposes of this study were to describe the prevalence and correlates of alcohol use and to examine the ability to predict alcohol use among rural sixth- and seventh-grade children. The sample consisted of 625 children from six schools in small Montana towns. Self-administered questionnaires contained measures of sociodemographic characteristics, self-concept, school attitudes, beliefs about the effects of alcohol, and alcohol use. Fifty-eight percent of the children reported using alcohol. Children's beliefs about alcohol were significantly correlated with alcohol use. Logistic regression analysis failed to identify a model having adequate sensitivity and specificity for classifying sixth- and seventh-grade students as "users" and "nonusers" based on variables assessed in Grades 3 and 4. Nevertheless, holding other variables constant, children who displayed both negative self-concept and negative school attitudes in Grades 3 and 4 were most likely to use alcohol in Grades 6 and 7. PMID- 8455991 TI - Measurement of recovery from myocardial infarction using heart rate variability and psychological outcomes. AB - This pilot study was designed to describe heart rate variability (HRV), anxiety, anger, denial, and depression during the first 4 days and 6 months after acute myocardial infarction (AMI). The sample was composed of 21 post-AMI males aged 40 to 83. State anxiety was elevated early. At 6 months it had significantly decreased. The nonpower measure of HRV, the Kleiger global standard deviation, was decreased to a mean score of 86 (SD = 29) msec during AMI and was 117 (SD = 30) msec at 6 months. Although there were no significant correlations between HRV, psychological response, age, and education, there were moderate correlations between HRV and state anger (r = .33), denial (r = .35), and education (r = .45). HRV, as measured by the power spectral density function of an autoregressive model, demonstrated an increased peak across the band of frequency associated with the high-frequency components of the parasympathetic system and a decreased peak across the band associated with the low-frequency components of the sympathetic system at 6 months as compared to the AMI period. PMID- 8455993 TI - Measurement of activity. AB - Activity is a phenomenon of concern to nursing. Although a wide variety of instruments have been used to measure activity, researchers have confronted barriers to its measurement in reliable, valid, and practical ways. Technological advances have stimulated theoretical and empirical developments in the study of activity by improving the physical instrumentation. This article presents an overview of methods used to measure human activity, with an emphasis on technological advances and the methods relevant to nursing. Self-report, behavioral observation, and mechanical and electronic activity measures are reviewed and critiqued. PMID- 8455994 TI - Correlates of fatigue in older adults with rheumatoid arthritis. AB - The purposes of this study were to describe the prevalence of fatigue, examine the association between fatigue and doctor visits, and identify correlates of fatigue in rheumatoid arthritis (RA). On average, a high degree of fatigue was reported to occur every day, to remain constant during the course of a week, and to most often affect walking and household chores. When controlling for disease severity and insurance coverage, respondents who reported more fatigue made more visits to the rheumatologist than those reporting less fatigue. A regression model with fatigue as the dependent variable revealed that the following variables explained a significant amount of variance: pain rating, functional status, sleep quality, female gender, comorbid conditions, and duration of disease. PMID- 8455995 TI - Nursing Times open learning programme. M6: managing the process of providing care. Part (ii): Clarifying aims (continuing education credit). PMID- 8455996 TI - HIV prejudice by employers is 'still rife'. PMID- 8455997 TI - London shake-up. Capital gains and losses. PMID- 8455998 TI - London shake-up. Preparing for change. PMID- 8455999 TI - London shake-up. Folding beds. PMID- 8456000 TI - London shake-up. Fighting back. PMID- 8456001 TI - Lost leaders. PMID- 8456003 TI - Professional development. In praise of appraisal. PMID- 8456002 TI - Shouting about AIDS. PMID- 8456004 TI - Professional development. A credit to the system. PMID- 8456005 TI - Making sense of underwater sealed drainage. PMID- 8456007 TI - Stillbirth. Who knows why? PMID- 8456006 TI - Lights out. PMID- 8456008 TI - Computing. Program for practice. PMID- 8456010 TI - Who needs care plans? PMID- 8456009 TI - Lifting action. Interview by Daloni Carlisle. PMID- 8456011 TI - Community care act. Close encounters. PMID- 8456012 TI - Learning disabilities. Gentle teaching. PMID- 8456013 TI - Learning disabilities. Facing up to the challenge. PMID- 8456014 TI - Abnormal right ventricular filling in patients with dilated cardiomyopathy. AB - Doppler echocardiograms of the tricuspid and mitral valves were recorded along with the electrocardiogram and respiration in six patients with dilated cardiomyopathy and 20 normal children. There was significant respiratory variation in right ventricular filling in the patients with dilated cardiomyopathy. Four variables of early diastolic right ventricular filling increased with inspiration: the peak E velocity (mean increase 55%, p < 0.05), the E/total area (mean increase 32%, p < 0.001), the E/A area (mean increase 74%, p < 0.001), and peak E/A ratio (mean increase 72%, p < 0.01), whereas the peak A velocity did not change significantly and the A/total decreased (mean decrease 27%, p < 0.001). Thus, abnormalities of right ventricular filling worsened during expiration and improved with inspiration. Inspiration enhances right ventricular venous return and thus improves indices of right ventricular filling in patients with cardiomyopathy. PMID- 8456015 TI - Doppler evaluation of femoral arteries in children after aortic balloon valvuloplasty or coarctation balloon angioplasty. AB - To assess long-term femoral artery complications after aortic balloon valvuloplasty or coarctation balloon angioplasty, we examined 19 children who were 3 weeks to 21 years old (mean 7.6 years) at the time of catheterization. Two dimensional and Doppler echocardiographic examinations of the common, superficial, and deep femoral arteries were performed at an average of 2.0 years after balloon dilatation. Pulsatility index (PI) was calculated as the maximum velocity minus the minimum velocity divided by the mean velocity. No patient was suspected clinically of having peripheral arterial disease prior to the echocardiographic examination. Fourteen patients had normal femoral arteries. Of these, 10 had normal two-dimensional and Doppler echocardiographic examinations of both femoral arteries. These patients had triphasic flow patterns (forward in systole, reverse in early diastole, forward in middiastole) and Pls of 3.7-41.6 (mean 9.5). Four of the 14 normal patients had abnormal pulsed Doppler examinations showing continuous forward flow and low Pls (1.7-3.5) reflecting residual coarctation (10-30 mmHg gradients). Five patients had abnormal femoral arteries. Of these, two had no visible obstruction by two-dimensional echocardiography and color-flow imaging but had abnormal pulsed Doppler patterns (continuous forward flow and low Pls of 2.5 and 2.9) only on the side of the balloon catheter insertion. Three of the five abnormal patients had visible obstructions by two-dimensional echocardiography and color-flow imaging and had abnormal pulsed Doppler patterns (continuous forward flow and low Pls from 1.1 3.6).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8456016 TI - Intraaortic balloon pump management of refractory congestive heart failure in children. AB - From December 1975 to September 1989, nine children, ages 0.6-15.8 years (mean = 8.1 years) and weighing 5-44 kg (mean = 24 kg), were identified as requiring intraaortic balloon pump support. Indications included ventricular failure refractory to maximal conventional therapy, inability to wean from cardiopulmonary bypass, and myocardial ischemia. Prior to insertion of the balloon catheter, mean systolic blood pressure was 64 mmHg, one to four cardiotonic medications were being administered, mechanical ventilation was being performed in eight patients, and mean urine output was 0.4 ml/kg/min in eight. Following balloon catheter insertion, mean urine output increased to 0.9 ml/kg/min. Four patients survived following discontinuation of the balloon catheter 12-96 h (mean = 59 h) after initiation. Though complications such as loss of distal lower extremity pulses, sepsis, thrombocytopenia, and abdominal distention were observed, most could be attributed to other causes. Thus, the intraaortic balloon pump is a valuable addition to conventional medical therapy in the treatment of refractory cardiogenic shock in children. PMID- 8456017 TI - Altered cardiac repolarization during exercise in congenital aortic stenosis. AB - The incidence of sudden death in children with congenital aortic stenosis (CAS) varies between 4 and 20%. In several syndromes sudden death is associated with a long QT interval in the electrocardiogram (ECG). The aim of the study was to evaluate the cardiac repolarization in CAS during stress. We included 40 children and young persons, 20 with CAS and 20 healthy controls. All underwent echocardiographic study and treadmill stress test. The QT and relative RR intervals were measured in leads II and V6 at rest and during exercise at preselected heart rates. Mean values of QT were compared by analysis of variance, Student's t-test, and linear regression method. No statistically significant differences in the resting ECG were found between the two groups, whereas during exercise the mean QT of the CAS group was significantly longer than in the controls (p < 0.05), except at a heart rate of 140 +/- 5. Our study demonstrates that patients with CAS have transiently altered cardiac repolarization when there are sudden variations in heart rate. Such a defect could predispose patients with CAS to fatal arrhythmias and sudden death. PMID- 8456018 TI - Obstructed total anomalous pulmonary venous connection. AB - With the advent of echocardiography, total anomalous pulmonary venous connection (TAPVC) can be readily diagnosed without much difficulty. However, noninvasive detection of the presence of pulmonary venous obstruction in TAPVC remains a difficult issue. During a 5.5-year period, 42 patients were found to have TAPVC by catheterization, surgery, and/or autopsy: 17 had supracardiac drainage, 13 paracardiac drainage, nine infracardiac drainage, and three mixed drainage. Obstruction to pulmonary venous drainage was found in 24 patients (57%). Patients with right isomerism tended to have a higher incidence of pulmonary venous obstruction than those with the usual atrial arrangement (80% vs. 44%, p < 0.05). Color Doppler combined with cross-sectional echocardiography provided accurate delineation of drainage sites in 93% cases (39 of 42). Among the 39 cases with correct echocardiographic delineation of the drainage site, obstruction was detected by echocardiography in 22 cases with a sensitivity of 100% (22 of 22) and a specificity of 85% (17 of 20). Therefore, complete echocardiography, including cross-sectional images and color Doppler proved to be a reliable tool in the detection of drainage sites and pulmonary venous obstruction in TAPVC. PMID- 8456019 TI - Mitral valve prolapse and body habitus in children. AB - Mitral valve prolapse has generally been associated in adults with a thin body habitus. However, prior studies used biased samples or limited anthropometric measures. In addition, no information has been available on the subjective assessment of body habitus and diagnosis of mitral valve prolapse, especially in children. We conducted a cross-sectional study on 813 children with uniform assessment of anthropometric measures and mitral valve prolapse. Consistent with research conducted on adults, those subjects with mitral valve prolapse were lighter, thinner, and had, on average, lower values for several, quantifiable anthropometric parameters with the exception of height. However, the subjective assessment showed that while the assessment did not differ by diagnosis, those subjects with mitral valve prolapse were never described as fat. These data support an association between mitral valve prolapse and slender body habitus and extends it to children, thus underscoring the clinical importance that a thin body habitus may be a marker for mitral valve prolapse throughout the age span. This association may partly explain the observed genetic distribution of mitral valve prolapse. PMID- 8456020 TI - Double-outlet single ventricle and an abdominal vascular mass: in utero diagnosis with pathological confirmation. AB - A fetal echocardiographic scan was performed when routine prenatal ultrasound screening failed to identify four cardiac chambers. The scan showed a single ventricle with an associated circoid varicosity. Because of these anomalies, amniocentesis was suggested and trisomy 18 confirmed. The presence of major cardiac structural anomaly should prompt careful and specific review of all fetal anatomy to screen for syndrome identification and consideration of amniocentesis. PMID- 8456021 TI - Coronary arteriovenous fistulae mimicking cardiovascular sequelae of Kawasaki disease. PMID- 8456022 TI - Evolution of traumatically acquired infracristal ventricular septal defect. AB - Nonpenetrating traumatic rupture of the ventricular septum is rare. This case report describes the evolution of such a lesion documented by echocardiography and color flow Doppler. Included is a brief discussion of postulated mechanisms for this rare phenomenon. PMID- 8456023 TI - "Superimposition" digital subtraction angiography: evaluation of total anomalous pulmonary venous connection. AB - Total anomalous pulmonary venous connection (TAPVC) has a relatively high surgical mortality, especially the infracardiac variety. A small left atrium may limit postoperative cardiac output. Superimposition of digitally subtracted angiographic (DSA) images may be used to define pulmonary venous anatomy, left atrial size, and its spatial relationship to the common pulmonary vein. The technique for acquiring superimposed digitally subtracted images and the results of two cases with infracardiac TAPVC are presented. We have found that this superimposition technique is easily performed and may provide important preoperative information in infants with TAPVC. PMID- 8456025 TI - Efficacy of 100 consecutive right ventricular endomyocardial biopsies in pediatric patients using the right internal jugular venous approach. AB - Indications for endomyocardial biopsy (EMB) in pediatric patients include cardiomyopathy and postheart transplant rejection surveillance. There have been few reports of the use of the internal jugular venous approach for right ventricular EMB in pediatric patients. In this study, we report our experience with 100 consecutive EMBs in pediatric patients using this approach. Indications for EMB were cardiomyopathy of unknown etiology in four patients, adriamycin cardiomyopathy in three patients, postheart transplant rejection surveillance in five patients, right ventricular outflow tract tumors in one patient, and sustained ventricular tachycardia in one patient. Histologic diagnoses of biopsy specimens included interstitial fibrosis, vasculopathy, hypertrophy, anthracycline cardiotoxicity, and various degrees of allograft rejection. All EMBs were performed successfully and without complications. We conclude that right ventricular EMB using the right internal jugular venous approach can be performed safely and successfully in pediatric patients as young as 2 months of age and repeatedly in patients as young as 8 years old. PMID- 8456024 TI - Retroperitoneal arteriovenous malformation, a rare cause of heart failure in infancy: consideration of therapeutic approaches. AB - We report an infant presenting with congestive heart failure secondary to a large retroperitoneal arteriovenous (AV) malformation. The heart failure was treated by catheter embolization of the feeding arterial vessels with Ivalon particles. Following resolution of the heart failure, a residual avascular mass remained. A biopsy revealed the diagnosis of an undifferentiated sarcoma that was successfully treated with chemotherapy and surgery. PMID- 8456026 TI - Gastrointestinal hemorrhage after combined percutaneous angioplasty of aortic coarctation and valvuloplasty of aortic stenosis in an infant. AB - Gastrointestinal hemorrhage has not been previously reported as a complication of dilating left-sided obstructive lesions. This report describes an infant who developed significant intestinal bleeding after combined angioplasty for aortic coarctation and valvuloplasty for aortic stenosis. PMID- 8456027 TI - An unusual case of cor triatriatum. AB - Cor triatriatum (CT) is a rare congenital cardiac anomaly. A case is presented of subdivided left atrium, corrected surgically, which can be considered a type of CT not previously reported. PMID- 8456028 TI - Pulmonary arteriovenous malformation in the newborn: a familial case. AB - Pulmonary arteriovenous malformation (PAVM) is a rare cause of cyanosis in the newborn with nine previously reported cases. Typical signs at presentation include cyanosis, murmur, and congestive heart failure. Abnormality on chest x ray is common with cardiomegaly, oligemia, and focal pulmonary density. There is a male predominance, unlike older children and adults with PAVM. Familial cases of PAVM have been reported with Osler-Weber-Rendu syndrome. We report a familial case of PAVM presenting in the newborn. PMID- 8456029 TI - Fontan's operation complications. PMID- 8456030 TI - Intrauterine closure of ventricular septal defects. PMID- 8456031 TI - Neurological complications of balloon angioplasty. PMID- 8456032 TI - Cardiac thrombi--plasma protein C deficiency as a possible risk factor. PMID- 8456033 TI - Supravalvar aortic stenosis--a constant feature of Williams-Beuren syndrome. PMID- 8456034 TI - The effect of treatment with angiotensin-converting enzyme inhibitors on survival of pediatric patients with dilated cardiomyopathy. AB - Outcome in 81 pediatric patients with dilated cardiomyopathy was reviewed to assess whether treatment with angiotensin-converting enzyme (ACE) inhibitors affected survival. Age at onset was 3.6 +/- 0.6 years. Twenty-seven children (group 1) were treated with ACE inhibitors. Conventional therapy was used in the remaining 54 patients (group 2). There were no significant differences between the two groups in age at onset, left ventricular shortening fraction, left ventricular end-diastolic pressure, or mean pulmonary artery pressure. Patients treated with ACE inhibitors had a significantly better survival during the first year (p < 0.05) with continuation of this trend throughout the second year (p = 0.06). Beyond 2 years there was a tendency toward better survival in ACE inhibitor-treated patients, but the differences were no longer significant (p = 0.14). These data, along with observations in adult patients with chronic cardiac failure, indicate that converting enzyme inhibitors have a beneficial effect on prolonging survival of infants and children with severe left ventricular dysfunction from dilated cardiomyopathy. PMID- 8456035 TI - Current epidemiology of comorbidity of psychiatric and addictive disorders. AB - Some major epidemiologic studies have assumed that treatment of the psychiatric symptoms will result in a lowered morbidity and mortality from the addictive disorders or, more specifically, that the addictive disorders are dependent on the psychiatric disorders and etiologically linked to them as an effect or secondary consequence. There is little systematic evidence beyond anecdotal and intuitive supposition to support this popular and only hypothetic position. The consequence is that to insist on the priority of the psychiatric disorder in diagnosis and treatment is to perpetuate artifactual prevalence rates for psychiatric comorbidity in addictive disorders, and to preclude the definitive treatment to reduce the psychiatric morbidity and mortality caused by addictive disorders. PMID- 8456036 TI - A hypothesis for a common neurochemical basis for alcohol and drug disorders. AB - Research findings clearly support a uniform theory for a neurochemical basis of drug and alcohol addiction. Data are available that document final common pathways for addictive behaviors in the limbic system in which neurotransmitters modulate the drive states, mood, and instinctual behaviors. The specific areas in the brain implicated in the loss of control inherent in the addictive use of multiple drugs and alcohol are the ventral tegmentum, nucleus accumbens, locus ceruleus, dorsal raphe nuclei, and the periaquaductal grey area. These sites contain cell bodies and receptors for dopamine, norepinephrine, serotonin, and endogenous opiates respectively, where multiple drugs and alcohol can often produce their effects. The acquired drive of addiction that arises spontaneously, repetitively, and relentlessly is manifested in the addictive behaviors of preoccupation, compulsivity, and relapse to drugs and alcohol. PMID- 8456037 TI - Recent advances in addictive disorders. Prevention. Current research and trends. AB - The AOD prevention programs of the 1990s should be resiliency-focused and include interventions of sufficient dosage and strength. Although some child behavioral technology exists to tackle successfully changes in resiliency, additional prevention strategies need to be developed and studied. In some way, the prevention field is hampered by the lack of sufficient research in the child and adolescent psychiatry and psychology fields, that includes transactional research in parenting and child rearing for high-risk youth. We simply do not know enough to determine how parents and other adults can best foster resilience in children. Questions that arise include how much to protect children from environmental stressors and how much to push them to confront new life stressors in the form of challenges to develop new skills or talents. There are no simple answers to these questions, but a number of useful guidelines could help parents and teachers to increase resilience in youth. Some of the guidelines currently being stressed include developing in youth an increased sense of responsibility for their own success, helping them to identify their talents, motivating them to dedicate their lives to helping society rather than feeling their only purpose in life is to be consumers, providing realistic appraisals and feedback for youth rather than graciously building up their self-esteem, stressing multicultural competence in an ever-shrinking world, encouraging and valuing education and skills training, increasing cooperative solutions to problems rather than competitive or aggressive solutions, and increasing a sense of responsibility for others and caring for others. Clearly, these are important objectives for creating the type of citizens that can make American strong in the twentieth century. PMID- 8456038 TI - Substance use risk factors for HIV infection. AB - The focus on reducing needle sharing by IVDUs as an HIV-control strategy is well supported by epidemiologic data. Because of this emphasis, however, the role of other HIV risk factors in drug use is sometimes overlooked. Although needle sharing by IVDUs undoubtedly will continue to be one of the greatest risk factor for HIV infection in drug users, other risk factors in HIV infection also are associated with drug use and may contribute significantly to the spread of HIV infection. It is clear that the role of drug use in AIDS is not limited to needle sharing by IVDUs. HIV infection can be transmitted by any type of needle use. Nonintravenous drugs (e.g., crack) and other risk factors (e.g., unprotected sex) also may play a role in the spread of HIV infection. Because of its dependence potential, crack may come to play a major role in HIV transmission, primarily because of its link to unprotected sexual behavior. PMID- 8456039 TI - Perspectives of effective treatment for alcohol and drug disorders. AB - Of the 1918 patients in the follow-up sample used for illustration, 63% reported total abstinence for the year after treatment, and an additional 24% reported at least 6 months of abstinence out of 12. Most relapses occurred during the first 6 month interval; 88% of patients who were abstinent the first 6 months maintained this status for the full year. Patients abusing drugs other than alcohol had much poorer outcomes than those abusing alcohol only, and this finding held up even when drug choice was controlled for sex and age of patients. Intravenous drug use was an important predictor of relapse, as was a history of antisocial behavior. A strong relationship to outcome was seen for patient participation in an aftercare program, and for weekly attendance at peer support group meetings. Emotional distress, relationship difficulties and family problems, financial difficulties, craving, and being around others who use alcohol and drugs are all seen as making the commitment to abstinence more difficult. There is clear evidence also that increased difficulty in these areas is predictive of later relapse. Comparisons of pretreatment and posttreatment measures of patient functioning revealed a decreased need for expensive health care services, such as hospitalization and emergency room care. The motor vehicle accident rate, traffic arrest rate, and criminal offense arrest rate all showed posttreatment declines. On-the-job problems also decreased dramatically following treatment. Posttreatment difficulties were disproportionately higher among patients who had returned to substance use than among patients who remained abstinent, documenting that successful treatment can have an affect in many areas that improve the quality of life for patients themselves (along with their families and communities) as well as reduce the high economic costs associated with alcohol and drug abuse in our society. Cost offsets for chemical dependency treatment are substantial and of broad scope; they also are related directly to the recovery rate. In general, the findings for outpatient programs tend to parallel those of the inpatients. Initial chemical severity and range of other clinical problems are lower, but significant reductions are noted. For both inpatients and outpatients monitored by CATOR, the posttreatment improvement in health care utilizations, reductions in work-related problems, and fewer arrests are related directly to recovery status. That is to say that recovering patients show significantly better improvement than relapsed patients. This means that treatment efficacy must be considered as a key element in estimating treatment benefits. PMID- 8456040 TI - Overview of pharmacologic treatment approaches for alcohol and other drug addiction. Intoxication, withdrawal, and relapse prevention. AB - Medication plays an increasingly important role in the treatment of alcohol and other drug addictions, in part because many patients do not respond to existing psychosocial treatment alone. This article provides a conceptual overview of current pharmacologic treatment approaches, and covers all three aspects of drug abuse--intoxication, withdrawal, and relapse prevention. PMID- 8456041 TI - Psychiatric aspects of substance use disorders in childbearing populations. AB - Prevention and treatment research in the field of perinatal addiction is at a point of high activity. At the same time, the fields of psychiatry and addiction treatment are undergoing a process of rapprochement. Psychiatrists have a knowledge base and unique perspective of value in framing questions that must be addressed in our quest for knowledge about substance use disorders in the child bearing population. In particular, detailed studies of psychiatric comorbidity, psychosocial characteristics associated with anticipated or actual pregnancy as a motivation for abstinence, treatment entry and recovery, and treatment approaches to past and ongoing victimization in the chemically dependent pregnant population are priorities. PMID- 8456042 TI - Clinical treatment matching models for dually diagnosed patients. AB - The models of serial, parallel, and integrated treatment should help administrators and clinicians to think through resources they have and ones they may be able to share. Certain patients should do better with one or another of the models, but these empirical approaches need testing. Though large controlled outcome studies for various models of dual diagnosis treatment are pending, pilot studies of interventions have been positive, and the need for designing and implementing sensible programs to address the dual diagnosis patient is here right now. PMID- 8456043 TI - Long-term recovery from alcoholism. AB - AA has demonstrated success in steadily increasing membership, with no loss of the proportion of those with over 5 years of sobriety. It has been recognized as effective long-term treatment for alcoholism by psychiatrists and psychoanalysts experienced in treatment of the addictions. The triennial membership surveys of AA have shown stability in 1. A 50% dropout rate within the first 3 months of starting AA. Only 41% of those in the first year will remain in the Fellowship for another year. 2. Roughly equal numbers of those with less than 1 year, 1 to 5 years, and over 5 years of sobriety, with an average length of sobriety of about 4 years. 3. Members having a sponsor (85%) and belonging to a home group (88%). 4. Attendance by members of about three meetings a week, regardless of duration of sobriety. 5. Members telling their doctor that they are in AA, but not helping him or her learn about the program. The survey data also indicate that AA is changing in the following ways: 1. The number of women members has increased to more than one third the total membership. 2. An increasing number of young people, under 30 years of age, to more than one fifth the total. 3. A decreasing number of older people, over 50 years of age, to just under one fourth the total. 4. An increasing number of members who were also addicted to other drugs (46%). Psychiatrists can use these data and knowledge of AA to 1. Increase the effectiveness of referrals of alcoholic patients to AA regardless of age, sex, race, or other characteristics. All are welcome and can benefit. 2. Deal with resistance, which occurs when patients begin to make contact with AA. 3. Help alcoholic patients through the difficult first year of sobriety. 4. Encourage their alcoholic patients to use AA as a program for personal growth and development. 5. Helping dually addicted patients use AA's singleness of purpose to facilitate their recovery. 6. Cooperate with alcohol and drug treatment programs in helping patients transfer to AA and work on an effective program of recovery. 7. Work with members of the local AA Treatment Facilities and Cooperation with the Professional Community Committees in helping alcoholic patients enter and use AA. 8. Provide psychiatric treatment for AA members in ways that support and sustain their program of recovery, especially by avoiding dependence-producing medications. PMID- 8456044 TI - Substance use and addiction among medical students, residents, and physicians. AB - When turning to our original questions, we offer the following tentative conclusions: 1. Although medical students as a group have a slightly higher percentage of use of alcohol, the pattern and prevalence of alcohol dependence is very consistent with their age mates in the general population. 2. There appears to be a pattern of increased alcohol problems with age among physicians and attorneys, as opposed to the general US population, which shows a diminution of alcohol-related problems over time. 3. There is no evidence for a marked increase in drug addiction and use of other prescription drugs among physicians. In fact, with the exception of tranquilizers and alcohol and psychedelics, which were used equally by physicians, medical students, residents, and their age mates, most other drug usage was slightly more prevalent in the general population than among students and residents. 4. Of particular concern is the finding of a lack of gender differences in problematic drinking with the pattern of female drinking rates for women approximating that of men by the end of medical school. 5. The most consistent predictive factor in alcoholism among physicians is the same as that in the general population: a family history of alcoholism. 6. Additional predictive factors of physician alcohol-related problems include a narcissistic type personality style that endorses the exploitation of others, a perception of low parental warmth in childhood, and particular stressors in the working or student environment such as being abused by others. Further predictive factors related to occupational stress await the results of ongoing perspective studies. 7. Physicians as a group probably respond more favorably to alcohol and drug addiction programs than do members of the general population. To a great extent, this is directly or indirectly due to the dire consequences of continued use, which include loss of hospital privileges and state licensure. It also would appear that required treatment and monitoring for alcohol and substance abuse has a positive effect on abstinence rates. PMID- 8456045 TI - Recent advances in addictive disorders. Special populations. Women, ethnic minorities, and the elderly. AB - The term special populations in the field of substance abuse refers to groups of patients who have unique treatment needs or who are underserved. This article reviews recent advances in substance abuse among three special population groups: women, ethnic minorities, and the elderly. The prevalence, problems with identification, issues in treatment, and treatment outcomes of substance abuse are discussed separately for each group. Finally, the heterogeneity of characteristics within each special population group is emphasized. PMID- 8456046 TI - A review of the substance use disorders section of the DSM-IV. AB - The DSM-IV work groups are the first to be given the opportunity to document carefully all stages of deliberations and make decisions based on carefully constructed and data-based criteria. The 5-year process has encouraged the use of detailed literature reviews and allowed members of the working groups to generate data from both MacArthur analyses and field trials to make the most appropriate decisions possible. The Substance Use Disorders Work Group was faced with a potentially infinite number of questions that could be asked. The guidelines presented at the beginning of this article, especially the focus on areas in which data are already available or might potentially be generated from a field trial, allowed our Work Group to focus on a limited number of questions. With rare exceptions, each of these areas was evaluated by the thorough literature reviews that have formed the chapters that make up this section of the Sourcebook. Our goals are relatively straightforward. It is important that clinicians, researchers, administrators, and those who will work the DSM-IV process have full access to the state of the literature that existed in the late 1980s and early 1990s, and the decision-making process that was used to address the issues that affected the DSM-IV. It is hoped that this article will not only help readers to understand both how and why the DSM-IV Substance Use Disorders Work Group made the relevant decisions, but will also encourage active research to answer more fully the potentially important questions raised in these reviews. PMID- 8456047 TI - Nicotine dependence. Diagnosis and treatment. AB - Psychiatrists must become more involved in the engagement and treatment of nicotine-dependent patients in their clinical practice because it is the number one killer in the DSM-III-R. There is no single treatment that will fit all psychiatric patients. Instead, a carefully tailored treatment plan is generated using the seven tier system to fit each patient and their psychosocial profile. Psychiatrists have the medical, social, and psychological training needed to manage nicotine-dependent patients. Although further research is needed, psychiatrists should no longer ignore their responsibility to treat nicotine dependence. PMID- 8456048 TI - Opiate addiction and the locus coeruleus. The clinical utility of clonidine, naltrexone, methadone, and buprenorphine. AB - Detoxification from opiate addiction has been a medical problem for as long as opiate drugs have been available. Treatment before the discovery of clonidine involved giving another opioid drug with less dangerous consequences of chronic use, such as the long-acting and orally administered once a day methadone, for another opioid mu agonist like heroin, which must be taken intravenously many times a day, thus making rehabilitation, work, and avoidance of hepatitis, HIV, and other illnesses difficult. Although methadone has proved to be very beneficial, it still has significant abuse potential. Naltrexone, because it blocks the effects of all opiates, has facilitated the transformation from addiction to a drug-free state for many recovering addicts. By alleviating withdrawal symptoms and by lessening the detoxification period, clonidine similarly has improved the prospect of recovery from opiate addiction. Relapse, whether withdrawal is treated with clonidine or other new agents or not, occurs with great regularity because repeated opiate use can induce a new acquired drive state--the drive for opiates. In addition, with powerful withdrawal symptoms during abstinence, opiate relapse is difficult to prevent without an adequate treatment program. The efficacy of clonidine and other medical magic bullets for withdrawal distress needs to be given as part of a long-term recovery program which not only allows the brain to re-establish normal homeostatic changes in the drug-free state but also provides sufficient motivation for new approaches to achieving and sustaining pleasurable existence. PMID- 8456049 TI - Cocaine. Diagnosis and treatment. AB - Significant advances in our understanding the phenomenology of cocaine addiction have occurred in the past 12 years such that we now recognize addiction to cocaine as a major public health problem. We now can diagnose cocaine addiction more accurately. Furthermore, cocaine addiction has stimulated creation and testing of novel treatment efforts because standard addiction treatment, although efficacious, is not as effective for cocaine addiction as compared with other addictions. Much remains to be learned. We need to clarify symptoms and syndromes associated with cocaine addiction to more precisely delineate true "comorbidity." Special attention is needed to understand the course and response to treatment in women addicted to cocaine. Also, work is needed to clarify the interaction of HIV, cocaine, and pharmacotherapy used to treat HIV. Regarding treatment, effort is needed to better understand the interactions among educational, group, cognitive-behavioral, and pharmacologic interventions. Specific attention is needed regarding use of 12-step recovery programs adapted for cocaine addicts with comorbid psychiatric disorders, such as schizophrenia, mood, and anxiety disorders. Finally, we need to better understand ways of attracting and holding cocaine addicts in treatment earlier in the course of their disorder. To that end, "nontraditional" interventions, such as acupuncture, deserve systematic examination as alternative methods of recruitment and intervention for certain populations of cocaine addicts. PMID- 8456050 TI - Anabolic steroids. AB - Anabolic-androgenic steroids are controlled substances that are taken illicitly to enhance physical appearance and performance. In addition to the desired somatic effects, reasonably good evidence suggests that AASs are capable of influencing mood and behavior. A myriad of adverse effects have been reported. Although many of these effects appear to reverse with cessation of use, fatalities due to suicides, homicides, liver disease, heart attacks, and cancer have been reported infrequently among illicit users. Although studies are needed to quantify more precisely the long-term consequences and risks of using AASs, patterns of illicit use are particularly troublesome. The use of extremely high doses, needles, counterfeit and veterinary drugs, and multiple steroidal and nonsteroidal drugs simultaneously may further enhance the risks of using AASs. The clinician should suspect AAS use in high-risk individuals who manifest any of the possible consequences described in this article. Laboratory tests can be valuable for detection of use and assessment of consequences. Treatment approaches may borrow from proven techniques employed with other substance abusers, but should also address the special value that physical attributes and body image have for the AAS user. PMID- 8456051 TI - Effects of danazol on DNA synthesis in rat prostate. AB - Effects of danazol, an isoxazol derivative of the synthetic steroid 17 alpha ethinyltestosterone, on activities of thymidylate synthetase and thymidine kinase, which are the DNA-synthesizing enzymes included in de novo and salvage pathways of pyrimidine metabolism, respectively, were investigated in rat prostate. Danazol markedly reduced plasma levels of luteinizing hormone and testosterone, and organ weight, both enzyme activities and bromodeoxyuridine immunoreactive cells which were regarded as the S-phase cells in prostate. These results indicate that danazol shows a property as a potent antigonadotropin. PMID- 8456052 TI - Is there a role for transrectal microwave hyperthermia of the prostate in the treatment of abacterial prostatitis and prostatodynia? AB - Transrectal microwave hyperthermia of the prostate was administered to 54 patients with chronic abacterial prostatitis or prostatodynia, who failed to respond to several courses of conventional therapies. Hyperthermia was delivered in 60-min long sessions with three randomly chosen regimens (1 session/week for 4 weeks; 1 session/week for 6 weeks; 2 sessions/week for 3 weeks). A prostatic temperature of 42.5 +/- 0.5 degrees C was maintained throughout the entire duration of each session. Patients were assessed pre- and postoperatively by scoring of subjective symptoms, uroflowmetry with flow nomograms, determination of residual urine volume, and transrectal ultrasonography of the prostate. At the long-term follow-up, the subjective symptom score was significantly improved in all patients. Fifty percent of the patients also reported an improvement of life quality, 47% reported their condition unchanged, and 3% reported deterioration, despite therapy. Urodynamic parameters improved but did not reach statistical significance. No major complications were encountered. Our preliminary data indicate that transrectal microwave hyperthermia of the prostate is a safe therapy that can be beneficial as a second line treatment in selected patients with recurring symptoms of abacterial prostatitis or prostatodynia, which do not respond to medical therapy. PMID- 8456053 TI - DNA quantitation of intraepithelial neoplasia and invasive carcinoma of the prostate. AB - The relation of prostatic intraepithelial neoplasia (PIN) or ductal dysplasia and the development of invasive prostate cancer is not clear. PIN, especially high grade, is usually associated with coexisting invasive cancer. Although some investigators have identified micro foci of invasive cancer evolving from PIN, the two are usually anatomically separated. Because of these distinct anatomic patterns, many investigators have concluded that PIN represents a "field effect" or marker of potential cancer progression, and is not directly involved in or leads to the development of invasive prostate cancer. We measured the DNA content in 49 foci of invasive cancer and 87 foci of PIN identified in 34 radical prostatectomies containing both PIN and invasive cancer. In addition, we examined 13 prostatectomies and 5 TUR specimens containing only PIN. We found that the majority of low grade PIN had normal or diploid range DNA and that approximately half of the high grade PIN were abnormal or aneuploid. Prostates with coexisting diploid range PIN and invasive cancer had an approximately equal number of diploid range and aneuploid invasive cancers. Conversely, almost all of the aneuploid PIN (usually high grade) had coexisting aneuploid invasive cancers. This would support the hypothesis that events in the progression of prostate cancer may be operative in both the development of PIN and invasive cancer. PMID- 8456054 TI - Induction of metallothionein by CdCl2 administration in rat prostate. AB - Metallothionein (MT) induction in the rat prostate gland was investigated by means of cadmium chloride administration. Ten-week-old male Wistar rats housed with cadmium free food were divided into three groups of six rats each and castrated. After seven days, 1 mg of testosterone propionate per rat was injected subcutaneously once a day until the end of the experiment. After three weeks, rats were injected daily for six days with a physiological saline, 0.3 mg/kg CdCl2, and 0.9 mg/kg CdCl2. MT concentration of the ventral and dorsal lobes was significantly increased in the three groups in proportion to the dose of CdCl2. MT content of the lateral lobe in three groups was also increased, but was not significantly different. Immunohistochemically, MT was induced mainly in the ventral lobe in the basal cells, and in the lateral and dorsal lobes in the epithelial cells. The weights of the prostatic lobes were similar in the three groups, and no histological change was identified. These results suggested that MT in the prostate was induced by cadmium administration, and that it may prevent cellular damage from harmful metals. PMID- 8456055 TI - The need for pharmacokinetics protocols in special cases. PMID- 8456056 TI - The pharmacology of botulinum toxin. PMID- 8456057 TI - Regulatory relevance of lipoproteins in interleukin-2 stimulated lymphocytes in vitro. AB - The regulatory role of very low density lipoproteins (VLDL) in de novo protein synthesis and in natural killer (NK) mediated cytotoxicity against cancer cells was evaluated in IL-2 activated peripheral blood mononuclear cells (PBL). Supplementing of VLDL to the incubation medium induced a potent dose-related inhibitory effect on the synthesis and secretion of (35S) labelled proteins. The maximal inhibitory response was observed at 50 micrograms/ml cholesterol VLDL. The effect of VLDL on the IL-2 induced ability of lymphocytes to kill cancer cells and to interfere with target cell proliferation was then evaluated. Maximal cytotoxicity was observed at 50 micrograms VLDL/ml as cholesterol. This VLDL dependent stimulatory effect was associated with a significant decrease in the proliferative effect of the medium conditioned by PBL. The possibility that VLDL mediate the regulation of immune functions by interacting with metabolic patterns expressed by IL-2 stimulated lymphocytes is discussed in light of these results. PMID- 8456058 TI - 5-Lipoxygenase gene expression in HL60 cells during differentiation with DMSO. AB - The model of promyelocytic leukemia cells HL60 was utilized to study the accumulation of 5-lipoxygenase mRNA during the cellular differentiation induced by DMSO. In the present study a strict correlation between the increase in state of differentiation of HL60 and accumulation of 5-lipoxygenase mRNA is demonstrated, indicating that HL60 cells are an interesting model for the study of drugs which could interfere with the synthesis of the enzyme. PMID- 8456059 TI - Splanchnic artery occlusion shock: vinblastine-induced leukopenia reduces tumour necrosis factor and thromboxane A2 formation, and increases survival rate. AB - This study was designed to assess the role of leukocytes in rats subjected to splanchnic artery occlusion for 45 min followed by reperfusion (SAO shock). Leukopenia was induced by an intravenous injection of vinblastine (1 mg/kg) 72 h before SAO shock. Survival rate (within 6 h), plasma levels of thromboxane B2 (TxB2), serum levels of tumour necrosis factor (TNF-alpha), and histological alteration of the intestinal tract were investigated. Control rats [white blood cells (WBC) = 10362 +/- 630/mm3] died within 2 h following ischaemia and reperfusion. Leukopenic (WBC = 1263 +/- 311/mm3) animals which underwent SAO shock survived more than 2 h and 50% of them were still alive after 6 h. Plasma TxB2 levels significantly increased in WBC count normal rats subjected to SAO shock (8.4 +/- 2.1 ng/ml), compared to sham animals (0.4 +/- 0.08 ng/ml); however SAO shock raised TxB2 levels significantly less (2.1 +/- 1.1 ng/ml) in leukopenic rats. Serum TNF-alpha, undetectable in sham-shocked rats (either with normal WBC count or without), rose up to 150 +/- 12 U/ml in shocked rate and to 45 +/- 5 U/ml (P < 0.01) in shocked animals with leukopenia. SAO shock induced a massive necrosis of the intestinal tract in rats with normal WBC count. Leukopenia prevented ileum necrosis in SAO shock. These data indicate that leukocytes play an important role in splanchnic artery occlusion and reperfusion. PMID- 8456060 TI - Gastrointestinal effects of single and repeated doses of ferrous sulphate in rats. AB - The gastrointestinal effects of single and repeated administration of ferrous sulphate was evaluated measuring faecal flora modifications and histology of stomach and duodenum of the rat. The acute experiments showed reversible histopathological lesions of stomach and duodenum with iron deposition and increase in faecal Cl. perfringens toxin after treatment with a high dose of FeSO4. The chronic experiment at lower doses showed no relevant histological damage, some iron deposition and strong alterations in faecal flora. A strong impact of oral FeSO4 on gastrointestinal environment was demonstrated. PMID- 8456061 TI - Role of Gd-DOTA in the evaluation and imaging of experimental blood-brain barrier disruption in brain edemas and their improvement after anti-inflammatory drugs treatment. AB - This study was carried out to evaluate the effect of new anti-inflammatory drugs in the treatment of brain edema in new models. Experimental brain edema was induced in rats by stereotaxic injection of phospholipase A2 into one hemisphere. Concentrations of intravenously injected gadolinium-DOTA in the lesioned hemisphere were three times as high as in normal rat hemisphere. Edema was reduced by treatment with anti-inflammatory drugs such as dexamethasone (P < 0.01) or an experimental benzamide drug (P < 0.02). Magnetic resonance imaging (MRI) was then used to evaluate edema reduction after administration of contrast medium. We observed weighted scans for control lesioned rats, a reduction of signal intensity after dexamethasone and no significant regression after the benzamide drug. For purposes of experimental brain edema research in rats, the MRI technique facilitates detection and evaluation of the anti-inflammatory activity of molecules crossing the blood-brain barrier. PMID- 8456062 TI - Introduction to backpropagation neural network computation. AB - Neurocomputing is computer modeling based, in part, upon simulation of the structure and function of the brain. Neural networks excel in pattern recognition, that is, the ability to recognize a set of previously learned data. Although their use is rapidly growing in engineering, they are new to the pharmaceutical community. This article introduces neurocomputing using the backpropagation network (BPN). PMID- 8456063 TI - Applications of capillary electrophoresis in pharmaceutical analysis. AB - The role of capillary electrophoresis (CE) in the analysis of peptide/proteins, chiral pharmaceuticals, and other small-molecule drugs has been reviewed. Potential uses of CE range from purity and structural confirmation to a micropreparative technique. Strategies for the prevention of protein wall adsorption include the use of extreme pH values, surface-modified capillaries, and high ionic strengths employing salts of alkali metals or by the addition of zwitterionic surfactants to the background electrolyte. Chiral separations of amino acids and other racemic pharmaceuticals have been achieved by micellar electrokinetic chromatography or by the introduction of cyclodextrins/modified cyclodextrins or other reagents to the running buffer. Applications of capillary electrophoresis to the analysis of small-molecule pharmaceuticals include determinations of drugs and/or excipients in various pharmaceutical preparations and the analysis of miscellaneous pharmaceuticals in standard solutions and biological fluids. The complementary nature of capillary electrophoresis and HPLC, in addition to future expectations of CE in pharmaceutical analysis, is discussed. PMID- 8456065 TI - Solid-state nuclear magnetic resonance (NMR) spectra of pharmaceutical dosage forms. AB - Solid-state 13C NMR spectra of tablets or capsules of prednisolone, enalapril maleate, lovastatin, simvastatin, ibuprofen, flurbiprofen, mefenamic acid, indomethacin, diflunisal, sulindac, and piroxicam were obtained in the CP/MAS mode at 50 MHz. These studies show that (1) solid-state NMR spectroscopy can detect the active ingredients in low-dose tablets and capsules; (2) the use of interrupted decoupling often results in suppression of resonances due to excipients, thereby allowing better detection of resonances from the drug; and (3) the technique permits discrimination between two prednisolone polymorphs present in tablets obtained from various manufacturers even though the tablets contain only approximately 5% (w/w) of the drug. PMID- 8456064 TI - Upper gastrointestinal pH in seventy-nine healthy, elderly, North American men and women. AB - Gastric and duodenal pH levels were measured in 79 healthy, elderly men and women (mean +/- SD = 71 +/- 5 years) under both fasted and fed conditions using the Heidelberg capsule technique. The pH was recorded for 1 hr in the fasted state, a standard liquid and solid meal of 1000 cal was given over 30 min, then the pH was measured for 4 hr postprandially. Results are given as medians and interquartile ranges: fasted gastric pH, 1.3 (1.1-1.6); gastric pH during the meal, 4.9 (3.9 5.5); fasted duodenal pH, 6.5 (6.2-6.7); and duodenal pH during the meal, 6.5 (6.4-6.7). Although fasted gastric pH, fasted duodenal pH, and duodenal pH during the meal differ statistically from those observed in young subjects, the differences are not expected to be clinically significant in terms of drug absorption for the majority of elderly subjects. Following a meal, gastric pH decreased from a peak pH of 6.2 (5.8-6.7) to pH 2.0 within 4 hr in most subjects. This rate of return was considerably slower than in young, healthy subjects. Nine subjects (11%) had a median fasted gastric pH > 5.0, and in five of these subjects the median pH remained > 5.0 postprandially. In this group, drugs and dosage forms which require an acidic environment for dissolution or release may be poorly assimilated. PMID- 8456066 TI - A fluorescence quenching method for estimating chelating groups in chelate conjugated macromolecules. AB - A terbium-dipicolinic acid (Tb-DPA) fluorescence quenching method for estimating free chelating groups conjugated to protein molecules was developed. This method was based on competitive displacement of DPA from binding to terbium by stronger chelating groups such as diethylenetriaminepentaacetic acid (DTPA), EDTA, nitrilotriacetic acid (NTA), DTPA-conjugated bovine serum albumin (BSA-DTPA), or DTPA-conjugated immunoglobulin G (IgG-DTPA), resulting in a significant reduction in terbium fluorescence. The chelating ability of the tested reagent, from high to low, was in the following order: BSA-DTPA > DTPA > IgG-DTPA > EDTA, NTA. At low terbium concentrations, the reduction was linear for DTPA. This fluorescence quenching method was not only rapid, simple, and as accurate as conventional radiosotopic or chromatographic methods, but also sensitive and reproductible. The detection limit was 10 nM for DTPA. The interrun coefficient of variation was at most 8%. The advantage of this method over other indirect methods is that it reveals the actual chelating ability of the tested macromolecule, unencumbered by complicating factors such as trace metal contamination and dimer/polymer formation during conjugation. PMID- 8456067 TI - The effect of phenol on the electrolyte flocculation of certain polymeric dispersions to thixotropic gels. AB - Aqueous dispersions of an acrylate-methacrylate, a water-insoluble copolymer, were prepared by a coacervation technique. Addition of sodium chloride (0.2 M) to the dispersion (10%, w/v) converted the system to a thixotropic gel which turns fluid on shaking and reverts to gel on standing. Phenol (0.03 M) inhibited the gelling effect of the electrolyte. Among the various phenolic compounds tested, phenol displayed the strongest and chlorocresol the weakest antigelling property. Sodium chloride reduced the electropotentials (index of particle-particle repulsiveness) of the polymer dispersions, while phenol increased the potentials. It is thought that the phenol solution acted as a dielectric which increased the interparticle repulsive potential, hence its antiflocculant effect. PMID- 8456068 TI - The pharmacokinetics and absorption of recombinant human relaxin in nonpregnant rabbits and rhesus monkeys after intravenous and intravaginal administration. AB - Recombinant human relaxin (rhRlx) is being developed as a potential cervical ripening agent to be applied intravaginally or intracervically prior to parturition. The pharmacokinetics and absorption of rhRlx were determined in nonpregnant female rabbits and rhesus monkeys after intravenous bolus (iv) and intravaginal administration of 0.1 mg/kg; additionally, rabbits were dosed with 0.5 mg/kg intravaginally. In rabbits (n = 6), mean (+/- SD) peak concentrations following iv bolus administration were 1554 +/- 296 ng/mL. The weight-normalized clearance (CL/W) was 5.9 +/- 0.4 mL/min/kg, initial volume of distribution (V1/W) was 57 +/- 9 mL/kg, and volume of distribution at steady state (Vss/W), assuming central compartment elimination, was 240 +/- 20 mL/kg. Vss/W could be as large as 2000 +/- 400 mL/kg without this assumption. The estimated amounts of rhRlx absorbed in rabbits following intravaginal administration of 0.1 and 0.5 mg/kg (n = 5/dose) were 3.1 +/- 1.4 and 0.7 +/- 0.3%, respectively; peak concentrations were 600 +/- 297 and 1066 +/- 584 pg/mL, respectively. In rhesus monkeys (n = 5) after iv administration, peak concentrations were 971 +/- 277 ng/mL; CL/W was 4.1 +/- 0.6 mL/min/kg, V1/W was 78 +/- 25 mL/kg, and Vss/W, assuming central compartment elimination, was 690 +/- 220 mL/kg. The upper limit for Vss/W was 1600 +/- 200 mL/kg when no assumptions were made regarding site (compartment) of elimination. After intravaginal administration (n = 6), two monkeys had undetectable rhRlx concentrations throughout the 48-hr sampling interval; one monkey had only one sample containing measurable rhRlx (51 pg/mL) at 24 hr; and three monkeys absorbed < 2% of the 0.1 mg/kg dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8456069 TI - Pulmonary delivery of free and liposomal insulin. AB - The effects of oligomerization and liposomal entrapment on pulmonary insulin absorption were investigated in rats using an intratracheal instillation method. The results indicated that both dimeric and hexameric insulins can be rapidly absorbed into the systemic circulation, producing a significant hypoglycemic response. Intratracheal instillation of insulin in two different oligomerized states has not resulted in any significant difference in the duration of hypoglycemic effect. However, the initial hypoglycemic response (first 10 min) obtained from intratracheal administration of 25 IU/kg hexameric insulin appears to be slower than that from the 25 IU/kg dimeric insulin, thereby suggesting that hexameric insulin may have a lower permeability coefficient across alveolar epithelium than the dimeric insulin. Intratracheal administration of insulin liposomes (dipalmitoylphosphatidyl choline:cholesterol, 7:2) led to facilitated pulmonary uptake of insulin and enhanced the hypoglycemic effect. Nevertheless, similar insulin uptake and pharmacodynamic response were obtained from both the physical mixture of insulin and blank liposomes and liposomally entrapped insulin. PMID- 8456070 TI - An in vitro/in vivo correlation for the disintegration and onset of drug release from enteric-coated pellets. AB - An empirical mass-transfer model for enteric-coating dissolution that uses in vivo dissolution data to characterize the pH-dependent solubility properties of the polymer film and a mass-transfer coefficient determined from in vivo dissolution or disintegration studies is developed. Once the in vivo mass transfer coefficient has been evaluated, it can be used in conjunction with in vitro dissolution data from other formulations to predict the in vivo time to disintegration and onset of drug release. Results of in vitro dissolution experiments using the USP basket dissolution apparatus and in vivo disintegration experiments using gamma scintigraphy with four enteric-coated pellet formulations are presented. The good agreement among the in vivo mass-transfer coefficients that were determined supports the validity of the model. PMID- 8456071 TI - Correlation between the disintegration time and the bioavailability of vitamin C tablets. AB - The goal of this study was to examine if the current USP disintegration standard for vitamin C tablets (max. 30 min in water at 37 degrees C with disks) is adequate or if a tighter disintegration standard (e.g., European compendia max. 15 min) should be recommended based on bioavailability considerations. Four formulations of 500-mg vitamin C tablets ranging in mean disintegration time from 9 to 120 min were compared with a standard vitamin C solution in a double-blind clinical trial with 15 subjects. The products were administered with a standard breakfast. The data show that a solution of vitamin C and a fast-disintegrating tablet (8-9 min) have equal but significantly lower bioavailability than tablets with longer disintegration times (30, 60, 120 min). Tablets with a mean disintegration time of 60 min showed the highest bioavailability. When the disintegration test was performed without disks, disintegration times increased so much that only the tablets with the fastest disintegration time (which were also the tablets with the lowest bioavailability) met the current USP disintegration time limit. Based on the results of the study, changes in the USP standard to omit the disks or to shorten the disintegration time will not achieve enhanced bioavailability but will result in reduced vitamin C absorption. In vitro dissolution of vitamin C tablets did not show the traditional relationship with bioavailability. PMID- 8456072 TI - Differential effects of anionic, cationic, nonionic, and physiologic surfactants on the dissociation, alpha-chymotryptic degradation, and enteral absorption of insulin hexamers. AB - Various surfactants were investigated to compare their effects on insulin dissociation, alpha-chymotryptic degradation, and rat enteral absorption. With a circular dichroism technique, sodium dodecyl sulfate (SDS) at a 5 mM concentration was found to completely dissociate porcine-zinc insulin hexamers (0.5 mg/ml) into monomers. The catalytic activity of alpha-chymotrypsin (0.5 microM) was also abolished by 5 mM SDS. When insulin was injected into the distal jejunum/proximal ileum segment of the rat, 5 mM SDS greatly enhanced its pharmacological availability, from a negligible value to 2.8%. Being a cationic surfactant, hexadecyl trimethylammonium bromide (CTAB) also efficiently dissociated insulin hexamers at concentrations of 1-5 mM. However, extensive charge-charge interaction was observed below a CTAB concentration of 0.6 mM, leading to insulin precipitation at a molar CTAB:insulin ratio of 1:1 to 2:1. An alpha-chymotryptic degradation study also revealed near-complete dissociation of insulin hexamers at 1 mM CTAB. Above 1 mM, however, CTAB acted as an enzyme inhibitor, most likely by means of charge repulsion. Enteral absorption studies showed a much lower pharmacological availability, only 0.29%. Nonionic surfactants such as Tween 80 and polyoxyethylene 9 lauryl ether were ineffective in dissociating insulin hexamers. Tween 80, at 5 mM, neither significantly altered the alpha-chymotryptic degradation pattern nor enhanced the enteral absorption of insulin. The relative effectiveness of different species of bile salts on insulin hexamer dissociation appeared to be similar. Sodium glycocholate at a 30 mM concentration also significantly increased insulin pharmacological availability, to 2.3%. A morphological study did not reveal any significant alteration of the rat intestinal mucosal integrity after exposure to 5 mM SDS for 30 min.2+ transport. PMID- 8456073 TI - Use of the gamma-ray perturbed angular correlation (PAC) technique for monitoring liposomal phospholipid bilayer integrity. AB - A membrane labeling method based on the principle of gamma-ray perturbed angular correction (PAC) was developed to monitor the structural integrity of liposomal membranes. The reporter group was 111In(III) complexed with the lipophilic diethylenetriaminepentaacetic acid (DTPA) derivative of dipalmitoylphosphatidylethanolamine (DPPE) embedded in the phospholipid bilayers of small unilamellar liposomes. Using this method, complete chemical digestion of the constituent phospholipids in these DTPA-conjugated liposomes by phospholipase A2 or phospholipase C in the presence of Ca2+ was found not to be followed by an immediate disruption of the liposomal membrane. Compared with other methods, the method developed permits the continuous noninvasive monitoring of the microenvironment of the lipid bilayer at the molecular level. It may potentially be applicable to evaluate liposomal fusion, screen for penetration enhancers under development for enhancement in mucosal drug penetration, and monitor liposomal degradation within the living animal. PMID- 8456074 TI - In vitro evaluation of calcium pectinate: a potential colon-specific drug delivery carrier. AB - Calcium pectinate (CaP)--the insoluble salt of pectin--can potentially be used as a colon-specific drug delivery system. The use of CaP as a carrier was based on the assumption that, like pectin, it can be decomposed by specific pectinolytic enzymes in the colon but that it retains its integrity in the physiological environment of the small bowel. The biodegradation of the carrier was characterized by monitoring the percent cumulative release of the insoluble drug indomethacin, incorporated into pectin or CaP matrices. Compressed tablets of pectin and indomethacin were analyzed for degradation in the presence of Pectinex 3XL, a typical pectinolytic enzyme mixture, and in the presence of the human colonic bacterium Bacteroides ovatus. The degradation of CaP-indomethacin tablets was assessed in the presence of Pectinex 3XL and in rat cecal contents. The release of indomethacin was significantly increased (end-time percentage cumulative release vs control) in the presence of Pectinex 3XL (89 +/- 20 vs 16 +/- 2 for CaP tablets), Bacteroides ovatus (12 and 22 vs 5.2 for pectin tablets), and rat cecal contents (61 +/- 16 vs 4.9 +/- 1.1 for CaP tablets). The weight loss of tablet mass was significantly higher (end-time dry weight vs control) in the presence of Pectinex 3XL (0 vs 75 +/- 6% of initial weight for CaP tablets). These findings indicate the potential of CaP, compressed into tablets with insoluble drug, to serve as a specific drug delivery system to the colon. PMID- 8456075 TI - Estimating the fraction dose absorbed from suspensions of poorly soluble compounds in humans: a mathematical model. AB - A microscopic mass balance approach has been developed to predict the fraction dose absorbed of suspensions of poorly soluble compounds. The mathematical model includes four fundamental dimensionless parameters to estimate the fraction dose absorbed: initial saturation (Is), absorption number (An), dose number (Do), and dissolution number (Dn). The fraction dose absorbed (F) increases with increasing Is, An, and Dn and with decreasing Do. At higher Dn and lower Do, the fraction dose absorbed reaches the maximal F, which depends only on An. The dissolution number limit on F can appear at both lower Do and lower Dn. Likewise, at higher Do and Dn, the fraction dose absorbed reaches a Do limit. Initial saturation makes a significant difference in F at lower Do and Dn. It is shown that the extent of drug absorption is expected to be highly variable when Dn and Do are approximately one. Furthermore, by calculating these dimensionless groups for a given compound, a formulation scientist can estimate not only the extent of drug absorption but also the effect, if any, of particle size reduction on the extent of drug absorption. PMID- 8456076 TI - Mass balance approaches for estimating the intestinal absorption and metabolism of peptides and analogues: theoretical development and applications. AB - A theoretical analysis for estimating the extent of intestinal peptide and peptide analogue absorption was developed on the basis of a mass balance approach that incorporates convection, permeability, and reaction. The macroscopic mass balance analysis (MMBA) was extended to include chemical and enzymatic degradation. A microscopic mass balance analysis, a numerical approach, was also developed and the results compared to the MMBA. The mass balance equations for the fraction of a drug absorbed and reacted in the tube were derived from the general steady state mass balance in a tube: [formula: see text] where M is mass, z is the length of the tube, R is the tube radius, Pw is the intestinal wall permeability, kr is the reaction rate constant, C is the concentration of drug in the volume element over which the mass balance is taken, VL is the volume of the tube, and vz is the axial velocity of drug. The theory was first applied to the oral absorption of two tripeptide analogues, cefaclor (CCL) and cefatrizine (CZN), which degrade and dimerize in the intestine. Simulations using the mass balance equations, the experimental absorption parameters, and the literature stability rate constants yielded a mean estimated extent of CCL (250-mg dose) and CZN (1000-mg dose) absorption of 89 and 51%, respectively, which was similar to the mean extent of absorption reported in humans (90 and 50%). It was proposed previously that 15% of the CCL dose spontaneously degraded systematically; however, our simulations suggest that significant CCL degradation occurs (8 to 17%) presystemically in the intestinal lumen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8456077 TI - A saturable transport mechanism in the intestinal absorption of gabapentin is the underlying cause of the lack of proportionality between increasing dose and drug levels in plasma. AB - Gabapentin (1-(aminomethyl)cyclohexaneacetic acid) is a neuroprotective agent with antiepileptic properties. The structure is small (molecular weight less than 200), is zwitterionic, and resembles an amino acid with the exception that it does not contain a chiral carbon and the amino group is not alpha to the carboxylate functionality. Gabapentin is not metabolized by humans, and thus, the amount of gabapentin excreted by the renal route represents the fraction of dose absorbed. Clinical trials have reported dose-dependent bioavailabilities ranging from 73.8 +/- 18.3 to 35.7 +/- 18.3% when the dose was increased from 100 to 1600 mg. The permeability of gabapentin in the rat intestinal perfusion system was consistent with carrier-mediated absorption, i.e., a 75 to 80% decrease in permeability when the drug concentration was increased from 0.01 to 50 mM (0.46 +/- 0.05 to 0.12 +/- 0.04). Excellent agreement was obtained between the actual clinical values and the predicted values from in situ results for the fraction of dose absorbed calculated using the theoretically derived correlation, Fabs = 1 - exp(-2Peff) by Amidon et al. (Pharm. Res. 5:651-654, 1988). The permeability values obtained for gabapentin correspond to 67.4 and 30.2% of the dose absorbed at the low and high concentrations, respectively. In the everted rat intestinal ring system, gabapentin shared an inhibition profile similar to that of L phenylalanine. Characteristics of gabapentin uptake included cross-inhibition with L-Phe, sensitivity to inhibition by L-Leu, stereoselectivity as evidenced by incomplete inhibition by D-Phe, and lack of effect by Gly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8456078 TI - Biotin uptake and transport across bovine brain microvessel endothelial cell monolayers. AB - Primary cultures of bovine brain microvessel endothelial cells (BMECs) were used to characterize blood-brain barrier (BBB) uptake and transport of biotin. Both the uptake and the transcellular transport of either radiolabeled or fluorescein conjugated biotin by confluent monolayers of BMECs were measured. Biotin uptake (Km = 123 microM) and bidirectional transport across BMEC monolayers was a saturable process and could be competed for by unlabeled biotin, biocytin, and biotinmethyl ester. Pantothenic and nonanoic acid were found not to be effective competitors for either biotin uptake or transport. The metabolic inhibitor, 2 deoxyglucose, had only small effects on the saturable apical-to-basolateral transport and apical uptake of biotin by BMECs. In contrast, basolateral-to apical transport of biotin was substantially attenuated by 2-deoxyglucose pretreatment. Results supported the existence of specific and saturable uptake and efflux carrier systems for biotin in BMEC monolayers. The function of these systems was dependent to some degree on the metabolic status of the BMECs. Our findings confirm the existence of a biotin uptake system at the BBB in vivo and provide the first indication of an efflux system for biotin in BMECs. PMID- 8456079 TI - Influence of dose range on degree of nonlinearity detected in dose proportionality studies for drugs with saturable elimination: single-dose and steady-state studies. AB - Deviation from proportionality occurs when the ratio of area under the curve (AUC) values is not equal to the ratio of administered doses. The degree of nonlinearity (fNL) can be quantitated as the ratio of AUCs divided by the ratio of doses. We explore positive deviation from proportionality (fNL > 1) using the classical Michaelis-Menten model of nonlinear elimination after a single dose (n = 1) or at steady state (ss). The degree of nonlinearity is related to the ratio of the highest dose to the lowest dose (Rd = DH/DL): fn = 1NL = (2 + Rd.epsilon)/(2 + epsilon), fssNL = (Rd.omega - 1)/(Rd.omega - Rd), where epsilon is the ratio of the initial concentration after the lowest dose to the Km (epsilon = DL/Km.V) and omega is the ratio of the Vmax to the average rate of input for the highest dose (omega = Vmax tau/F.DH). From these relationships, we find that (1) for single-dose studies, Km is the important Michaelis-Menten parameter, while Vmax is important at steady state; (2) the degree of nonlinearity cannot exceed the ratio of doses in single-dose studies, and when doses in extreme excess of Km.V are chosen, the degree of nonlinearity is equal to the dose range; and (3) at steady state, the degree of nonlinearity can exceed the ratio of doses and approaches infinity as the average input rate approaches Vmax. Literature data (phenytoin and ethanol) support these findings. We conclude that the degree of nonlinearity is not a useful measure of nonlinearity in and of itself and propose percentage saturation as being more informative. PMID- 8456080 TI - Selective effect of adjuvant arthritis on the disposition of propranolol enantiomers in rats detected using a stereospecific HPLC assay. AB - Nonstereospecific studies have indicated that the pharmacokinetics of propranolol (PR) are altered in inflammatory conditions such as arthritis. However, as the kinetics and dynamics of PR are stereoselective, we examined the effect of adjuvant arthritis (AA) on the disposition of the individual enantiomers. A novel normal-phase stereospecific HPLC assay for PR was developed involving chiral derivatization with S-(naphthyl)ethyl isocyanate and fluorescence detection. Oral and iv doses of racemic PR were administered to control and AA rats (n = 6). AA had no significant effect on either clearance or S:R ratio after iv doses. On the other hand, after oral doses, clearance was significantly decreased in AA. Although significant for both enantiomers, this effect was more pronounced on the less active R-enantiomer. The AUC R:S ratio was, therefore, significantly altered (AA, 14 +/- 3.0; control, 4.3 +/- 1.2). Increased total (S+R) plasma concentrations of PR in AA, possibly due to a reduced intrinsic clearance, therefore, reflect mainly increased concentrations of the less active R enantiomer. PMID- 8456081 TI - Effect of plasma protein binding on kinetics of capillary uptake and efflux. AB - We examined the effect of plasma protein binding on the kinetics of organ accumulation and washout of drugs using the single-pass Kety-Renkin-Crone capillary model. An equation relating the accumulation and washout rate constant (k) with the plasma unbound fraction (fu) was derived. Simulations showed that k was highly dependent on fu if capillary permeability was high but was independent of fu if permeability was low. The effect of plasma protein binding was to increase the rate of tissue accumulation and washout of drug but to decrease the equilibrium amount of drug taken up by the tissue, both effects mediated via a decrease in the volume of distribution. This model was used to analyze published data on the effect of plasma protein binding on the kinetics of accumulation and washout of isradipine and propafenone in the isolated perfused heart preparation. The relationship between k and fu and the directly measured volume of distribution were in accordance with the model. Although more complex models relating k and fu could be proposed, taking into account unequal flows in capillaries, slow dissociation of ligand from protein, and unstirred layer constraints, this simple model appears adequate for describing the effect of fu on myocardial accumulation and washout of isradipine and propafenone. PMID- 8456082 TI - A spectrophotometric modification of the Winkler method for measurement of dissolved oxygen. PMID- 8456083 TI - Physical chemical properties of alpha styryl carbinol antifungal agents. PMID- 8456084 TI - Scaleup of immediate release oral solid dosage forms. PMID- 8456085 TI - Multiple vascular profiles in the umbilical cord; an indication of maternal smoking habits and intrauterine distress. AB - A total of 644 umbilical cords were examined over a period of 5 years, 40 cords (6.2 per cent) showed more than the normal three vascular profiles on cross section. Both the umbilical arteries and vein showed multiple profiles, although arterial profiles were far more commonly multiple. Clinical data were correlated with the histological findings. Heavy smoking was significantly associated with multiple vascular profiles. Maternal age and rhesus group were not significantly related however, but there was some association with primiparity. Fetuses with a gestational age between 33 and 38 weeks were significantly more likely to have multiple vessels than either fetuses beyond 38 weeks or less than 33 weeks gestation. Multiple channels also occurred significantly more frequently in still birth than in live birth cords. We suggest that multiple vascular profiles represent a response to intrauterine hypoxia. Inflammation of the cord was associated with multiple channels and suggests linkage between these two indications of fetal distress. PMID- 8456086 TI - Retinoic acid decreases attachment of JAR choriocarcinoma spheroids to a human endometrial cell monolayer in vitro. AB - The ability of retinoic acid (RA) to modulate attachment of JAR choriocarcinoma multicellular spheroids to monolayers of a human uterine epithelial cell line (RL95-2) was examined using a centrifugal force-based adhesion assay. Exposure of choriocarcinoma spheroids to RA (10(-7) to 10(-5) M) over a 3-day culture period resulted in a dose-dependent decrease of attachment. Significant decreases in attachment were detected after 30 min (75 per cent versus 25 per cent) and 1 h (92 per cent versus 26 per cent) of confrontation-culture between choriocarcinoma and uterine cells for control versus 10(-5) M RA; by 5 h 100 per cent spheroid attachment was detected in all treatment groups. RA had no effect on cell proliferation in JAR spheroids, but 10(-5) M RA treatment induced a fivefold increase in secretion of human chorionic gonadotrophin (hCG), a known marker of conversion of cytotrophoblast to syncytiotrophoblast-like cells. These findings demonstrate that RA modulates cellular attachment and differentiation in choriocarcinoma spheroids in vitro. PMID- 8456087 TI - CD44 in human placenta: localization and binding to hyaluronic acid. AB - CD44, a receptor for hyaluronic acid (HA), has been identified in the stroma of stem and terminal chorionic villi of human term placenta. The CD44 glycoprotein antigen, isolated from placenta by affinity to monoclonal antibody (mAb) 50B4, consisted mainly of species of M(r) 85,000 and 200,000. Radiolabelled CD44 bound specifically to HA attached to plastic, predominantly via the M(r) 85,000 species; this binding was inhibited by soluble HA and hyaluronidase. The binding of CD44 to HA was also inhibited by mAb 50B4 and IM7.8.1, which recognize epitopes of cluster I and II respectively, but was not blocked by a polyclonal antibody to peptide 18-30 of the B loop (residues 12-101). These results suggest that the portion of the B loop of CD44 implicated in the binding to HA is between amino acids 31-101 and that epitopes located outside the B loop, such as that recognized by mAb IM7.8.1 (between residues 132-215), contribute to this interaction. The presence of a functional CD44 molecule in the human term placenta suggest a role for this molecule in situ in the stabilization and orientation of HA network important in the maintenance of the structural integrity of the placenta. PMID- 8456088 TI - The rate of blood flow through the inverted yolk sac placenta of the anesthetized guinea-pig. AB - The rate of blood flow through the yolk sac placenta of late gestation guinea-pig fetuses was estimated by an indirect approach: radionuclide-labelled microspheres were injected in a saphenous vein and the ratio of radioactivity in the yolk sac to that in one of several reference organs was calculated. The ratio was then multiplied by a constant derived from separate experiments in which blood flows to the fetal abdominal organs and chorioallantoic placenta were determined. Stomach blood flow was positively correlated to arterial oxygen content (r = 0.74, P < 0.05), as was the weight-specific splenic blood flow (r = 0.66, P < 0.05). Perfusion of the small and large bowel, kidneys and chorioallantoic placenta was not related to arterial pH or oxygen content and these organs were used as references for the estimation of vitelline blood flow. A positive correlation was found between yolk sac blood flow and arterial oxygen content (r = 0.91, P < 0.01). In normoxaemic guinea-pig fetuses, yolk sac blood flow is 100 300 microliters per min. PMID- 8456089 TI - Changes in oxygen diffusive conductances of human placentae during gestation (10 41 weeks) are commensurate with the gain in fetal weight. AB - Evidence is adduced that the oxygen diffusive conductance of the human placenta increases during gestation. Results are based on placentae from 10 weeks to term. The diffusion pathway is analysed as six discrete tissue compartments arranged in series. Stereological and physicochemical data are used to determine partial, total and specific diffusive conductances for each organ and for its tissue compartments. During gestation, maternal and fetal vascular spaces became more voluminous and exchange surface areas of villi and capillaries expanded. Both were manifestations of placental growth and development. Maturation of villi was evident as decreases in effective diffusion distances across the trophoblast and villous stroma. These alterations contributed to improvements in partial and total conductances which continued towards term. Changes within the trophoblast and stroma were particularly influential in determining total conductance. Those on maternal and fetal sides of the diffusion pathway were less important. The rise in total conductance was related directly to the rise in fetal weight. Specific diffusive conductance was constant throughout gestation. PMID- 8456090 TI - Paracellular permeability pathways in the human placenta: a quantitative and morphological study of maternal-fetal transfer of horseradish peroxidase. AB - Physiological data indicate that both a transcellular and a paracellular pathway are available for transfer across the human placenta but the morphological correlate of the latter is uncertain. We measured the permeability of the dually perfused human placental cotyledon to the predominantly cationic protein horseradish peroxidase (MW 40,000), to the neutral polymer 14C-dextran (MW 50 70,000) and to the extracellular space marker creatinine (MW 113). Following fixation and cytochemistry, we used brightfield microscopy to localize peroxidase reaction product within the same tissue. Steady state unidirectional maternofetal clearance (Kmf) for the peroxidase (0.90 +/- 0.27 microliters/min/g, n = 9) was not significantly different from that for 14C-dextran (0.95 +/- 0.07 microliters/min/g, n = 3) suggesting that charge does not markedly influence peroxidase permeability. The Kmf for creatinine was 13.1 +/- 2.5 microliters/min/g (n = 9); these permeability data are similar to those reported for the placenta in vivo. Microscopically, peroxidase reaction product was localized to the microvillous surface of the syncytiotrophoblast of most villi and to the trophoblastic basement membrane and connective tissue cells of the villous core in a few villi. The reaction product was also associated with fibrin containing deposits attached to the villous core at sites of discontinuity of the syncytial epithelium. The staining pattern within the deposits was consistent with a diffusion gradient of the peroxidase. These fibrin-containing deposits at discontinuities in the syncytiotrophoblast may provide one paracellular route for peroxidase diffusion from the intervillous space into the villous core. PMID- 8456092 TI - Glycine uptake by microvillous and basal plasma membrane vesicles from term human placentae. AB - Like most amino acids, glycine is present in higher concentrations in the fetus than in the mother. Unlike most amino acids, animal studies suggest fetal concentrations of glycine are minimally in excess of those required for protein synthesis. Abnormal glycine utilization has also been demonstrated in small-for gestational age human fetuses. The mechanism(s) of glycine uptake in the human placenta are unknown. In other mammalian cells glycine is a substrate for the A, ASC and Gly amino acid transport systems. In this study human placental glycine uptake was characterized using microvillous and basal plasma membrane vesicles each prepared from the same placenta. In both membranes glycine uptake was mediated predominantly by the sodium-dependent A system. Competitive inhibition studies suggest that in microvillous vesicles the small percentage of sodium dependent glycine uptake not inhibited by methylaminoisobutyric acid (MeAIB) shares a transport system with glycine methyl ester and sarcosine, substrates of the Gly system in other tissues. In addition there are mediated sodium independent and non-selective transport mechanisms in both plasma membranes. If fetal glycine availability is primarily contingent upon the common and highly regulated A system, glycine must compete with many other substrates potentially resulting in marginal fetal reserves, abnormal utilization and impaired growth. PMID- 8456091 TI - Platelet aggregation inhibiting activity of human placental chorioepithelial brush border membrane vesicles. AB - We investigated the platelet aggregation inhibiting activity of human placental brush border membrane vesicles (BBMV) and obtained the following results. A strong platelet aggregation inhibiting activity existed in placental BBMV. The BBMV inhibited the platelet aggregation induced by ADP, arachidonic acid, collagen and ristocetin in a dose-dependent manner. The protein concentration of BBMV giving 50 per cent inhibition was 52 +/- 6 micrograms/ml for ADP-induced platelet aggregation, 21 +/- 2 micrograms/ml for arachidonic acid-induced platelet aggregation, 19 +/- 2 micrograms/ml for collagen-induced platelet aggregation and 107 +/- 9 micrograms/ml for ristocetin-induced platelet aggregation. There was a high level of ADP degrading activity (ADPase activity) in the placental BBMV. ADP degrading activity of the BBMV: 10.5 +/- 0.5 mumol/mg protein/min was 21 times greater than that of homogenate of the placental villi. The placental BBMV inhibited platelet TXA2 production. In the 40 micrograms/ml protein concentration of placental BBMV, platelet TXA2 production was almost completely inhibited. PMID- 8456093 TI - Characterization of human placental activity for transport of taurocholate, using brush border (microvillous) membrane vesicles. AB - The uptake of taurocholate into brush border membrane vesicles prepared from human full term placenta was studied using a rapid filtration technique. The taurocholate uptake into brush border membrane vesicles was sensitive to extravesicular osmolarity, and pre-incubation of the brush border membrane vesicles with the taurocholate increased the uptake of taurocholate into the brush border membrane vesicles. These findings indicate that the uptake of taurocholate by brush border membrane vesicles represents transport into vesicles. The uptake of taurocholate into vesicles was not dependent on Na+ electrochemical gradient (extravesicular > intravesicular). But this uptake was markedly increased when the intravesicular space was rendered electrically more positive by the use of lowly permeant anions or valinomycin-induced K+ diffusion membrane potentials. These findings indicate that the taurocholate transport into brush border membrane vesicles was dependent on membrane potential. The initial rate of taurocholate transport into brush border membrane vesicles exhibited saturation kinetics with respect to the taurocholate concentration, an apparent Km of 67 microM and Vmax of 0.30 nmol/mg protein/20 sec were calculated. PMID- 8456094 TI - Pitch diversity in alpha-helical coiled coils. AB - Two complementary methods for measuring local pitch based on heptad position in alpha-helical coiled coils are described and applied to six crystal structures. The results reveal a diversity of pitch values: two-stranded coiled coils appear to have pitch values near 150 A; the values for three- and four-stranded coiled coils range closer to 200 A. The methods also provide a rapid and sensitive gauge of local coiled-coil conformation. Polar or charged residues in the apolar interface between coiled-coil helices markedly affect local pitch values, suggesting a connection between pitch uniformity and coiled-coil stability. Moreover, the identification of a skip residue (heptad frame shift) in the hemagglutinin glycoprotein of influenza virus (HA) allows interpretation of local pitch changes. These results on relatively short coiled-coil structures have relevance for the much longer fibrous proteins (many of which have skip residues) whose detailed structures are not yet established. We also show that local pitch values from molecular dynamics predictions of the GCN4 leucine zipper are in striking agreement with the high-resolution crystal structure--a result not readily discerned by direct comparison of atomic coordinates. Taken together, these methods reveal specific aspects of coiled-coil structure which may escape detection by global analyses of pitch. PMID- 8456095 TI - Beta VI turns in peptides and proteins: a model peptide mimicry. AB - To investigate the role of proline in defining beta turn conformations within cyclic hexa- and pentapeptides we synthesized and determined the conformations of a series of L- and D-proline-containing peptides by means of 2D NMR spectroscopy and restrained molecular dynamics simulations. Due to cis/trans isomerism the L proline peptides adopt at least two different conformations that are analyzed and compared to the structures of the corresponding D-proline peptides. The cis conformations of the compounds cyclo(-Pro-Ala-Ala-Pro-Ala-Ala), cyclo(-Arg-Gly Asp-Phe-Pro-Gly-), cyclo(-Arg-Gly-Asp-Phe-Pro-Ala-), cyclo (-Pro-Ala-Ala-Ala-Ala ), and cyclo(-Pro-Ala-Pro-Ala-Ala-) form uncommon beta VI turns that mimic the turn geometries found in crystallographically refined protein structures at such a detailed level that even preferred side chain orientations are reproduced. The ratios of the cis/trans isomers are analyzed in terms of the steric demand of the proline-following residue. The conformational details derived from this study illustrate the importance of the examination of small model compounds derived from protein loop regions, especially if bioactive recognition sequences, such as RGD (Arg-Gly-Asp), are incorporated. PMID- 8456096 TI - Multiple-site titration and molecular modeling: two rapid methods for computing energies and forces for ionizable groups in proteins. AB - Computer models of proteins frequently treat the energies and forces associated with ionizable groups as if they were purely electrostatic. This paper examines the validity of the purely electrostatic approach, and concludes that significant errors in energies can result from the neglect of ionization changes. However, a complete treatment of ionizable groups presents substantial computational obstacles, because of the large number of ionization states which must be examined in systems having multiple interacting titratable groups. In order to address this problem, two novel methods for treating the energetics and forces associated with ionizable groups with a minimum of computer time have been developed. The most rapid method yields approximate energies by computing the free energy of a single highly occupied ionization state. The second method separates ionizable groups into clusters, and treats intracluster interactions exactly, but intercluster interactions approximately. This method yields both accurate energies and fractional charges. Good results are obtained in tests of both methods on proteins having has many as 123 ionizable groups. The more rapid method requires computer times of 0.01 to 0.34 sec, while the more accurate method requires 0.7 to 15 sec. These methods may be fast enough to permit the incorporation of ionization effects in iterative computations, such as energy minimizations and conformational searches. PMID- 8456097 TI - The structure of a thermally stable 3-phosphoglycerate kinase and a comparison with its mesophilic equivalent. AB - The structure of the phosphoglycerate kinase (PGK) from Bacillus stearothermophilus, a moderate thermophile, has been determined and compared with that of its mesophilic equivalent from yeast. The Bacillus enzyme structure was solved by molecular replacement and improved using constrained rigid-body, molecular dynamics and conventional refinement procedures. The refinement residual, calculated using all the measured data between 8 and 1.65 A, is 0.18(1). The stereo chemical deviations of the final model from ideality are 0.01 A for both bonds and planes. The mid-point temperatures of the Bacillus and yeast enzymes are 67 and 53 degrees C, respectively. Differential scanning calorimetry indicates that the energy difference (delta delta G) between the mesophilic and thermophilic enzymes is of the order of 5 kcal mol-1 at room temperature. The structure comparison indicates that the features most likely to be responsible for the increased thermal stability of the Bacillus enzyme are the increased internal hydrophobicity, additional ion pairs, and better alpha-helix stability resulting from the removal of helix destabilizing residues and extra helix dipole/helix side chain ionic interactions. PMID- 8456098 TI - Characterization of the backbone dynamics of an anti-digoxin antibody VL domain by inverse detected 1H-15N NMR: comparisons with X-ray data for the Fab. AB - The dynamic behavior of the polypeptide backbone of a recombinant antidigoxin antibody VL domain has been characterized by measurements of 15NT1 and T2 relaxation times, 1H-15N NOE values, and 1H-2H exchange rates. These data were acquired with 2D inverse detected heteronuclear 1H-15N NMR methods. The relaxation data are interpreted in terms of model free spectral density functions and exchange contributions to transverse relaxation rates R2 (= 1/T2). All characterized residues display low-amplitude picosecond time-scale librational motions. Fifteen residues undergo conformational changes on the nanosecond timescale, and 24 residues have significant R2 exchange contributions, which reflect motions on the microsecond to millisecond time-scale. For several residues, microsecond to millisecond motions of nearby aromatic rings are postulated to account for some or all of their observed R2 exchange contributions. The measured 1H-2H exchange rates are correlated with hydrogen bonding patterns and distances from the solvent accessible surface. The degree of local flexibility indicated by the NMR measurements is compared to crystallographic B-factors derived from X-ray analyses of the native Fab and the Fab/digoxin complex. In general, both the NMR and X-ray data indicate enhanced flexibility in the turns, hypervariable loops, and portions of beta-strands A, B, and G. However, on a residue-specific level, correlations among the various NMR data, and between the NMR and X-ray data, are often absent. This is attributed to the different dynamic processes and environments that influence the various observables. The combined data indicate that certain regions of the VL domain, including the three hypervariable loops, undergo dynamic changes upon VL:VH association and/or complexation with digoxin. Overall, the 26-10 VL domain exhibits relatively low flexibility on the ps-ns timescale. The possible functional consequences of this result are considered. PMID- 8456099 TI - Binding interactions of kistrin with platelet glycoprotein IIb-IIIa: analysis by site-directed mutagenesis. AB - The binding interactions between platelet fibrinogen receptor, glycoprotein (GP) IIb-IIIa, and kistrin, a snake venom disintegrin protein that contains the adhesion site recognition sequence Arg-Gly-Asp (RGD) and potently inhibits platelet aggregation, have been investigated by site-directed mutagenesis of a synthetic kistrin gene. Kistrin was expressed as a fusion protein in Escherichia coli under control of the alkaline phosphatase promoter. This construction included the stII signal sequence to direct secretion to the periplasmic space and one synthetic (Z) domain of Staphylococcal protein A to allow affinity purification using IgG Sepharose. Kistrin was cleaved from the Z-domain by site specific proteolysis using a mutant subtilisin BPN' and purified by reverse-phase HPLC. This approach facilitated the rapid purification of a set of 43 alanine replacement mutants whose relative affinity for GP IIb-IIIa was measured by competition with immobilized kistrin and by inhibition of platelet aggregation in human platelet-rich plasma. Alanine replacements at R49, G50, and D51 led to weaker inhibitors of platelet aggregation by 90-fold, 2-fold, and > 200-fold, respectively. The conservative D51E mutant was still > 100-fold less potent whereas R49K had a minor effect (1.8-fold), implying the critical nature of the aspartate for high affinity binding. However, mutations outside of the RGD region led to proteins indistinguishable from kistrin, suggesting no substantial secondary binding interactions. Furthermore, reduced kistrin is not active. We therefore propose that a favorable conformation of the RGD region alone is responsible for the high affinity binding of kistrin to GP IIb-IIIa. PMID- 8456100 TI - Site-specific proteolytic cleavage of Ku protein bound to DNA. AB - Ku protein, a relatively abundant nuclear protein associated with DNA of mammalian cells, is known to be a heterodimer with subunits of 85 and 72 kDa which binds in vitro to DNA ends and subsequently translocates along the molecule. The functional role played by this protein in the cell, however, remains to be elucidated. We have observed here that Ku protein, purified from cultured monkey cells, is the target of specific endoproteolysis in vitro, by which the 85 kDa subunit is cleaved at a precise site while the 72 kDa subunit remains intact. This cleavage releases an 18 kDa polypeptide and converts Ku protein into a heterodimer composed of the 72 kDa subunit associated with a 69 kDa fragment from the 85 kDa subunit. The proteolyzed form of Ku protein, denoted Ku', has DNA binding properties similar to those of Ku protein. The proteolytic mechanism, which is inhibited by leupeptin and chymostatin, is extremely sensitive to ionic conditions, in particular to pH, being very active at pH 7.0 and completely inhibited at pH 8.0. In addition, cleavage occurs only when Ku protein is bound to DNA, not free in solution. We suggest that in vivo, such proteolysis might be necessary for Ku protein function at some stage of the cell cycle. PMID- 8456101 TI - Transport of folates and antifolates in liver. AB - The characteristics and mechanisms of hepatic transport of folates and antifolate cancer drugs, for example, methotrexate, have been studied in perfused liver, isolated hepatocytes (in both freshly isolated cells and in primary cell culture), and membrane vesicles isolated from the basolateral membrane. Both naturally occurring folates and antifolates are taken up by the perfused liver and secreted into bile by apparently active processes, since these compounds are concentrated in liver and bile compared with the perfusate. Transport of the naturally occurring folate 5-methyltetrahydrofolate in isolated hepatocytes and basolateral membrane vesicles is via cotransport with hydrogen ions, is electroneutral, and is inhibitable by other reduced folates and by methotrexate. Transport of methotrexate is by a multispecific anion carrier, is electrogenic, and is not inhibitable by reduced folates (e.g., 5-methyl- and 5 formyltetrahydrofolate). Thus, the hepatocyte has separate systems for uptake of the naturally occurring, reduced folates and for the 4-amino-substituted antifolates. PMID- 8456102 TI - Growth hormone-binding proteins. PMID- 8456103 TI - Effect of Losartan, a nonpeptide angiotensin II receptor antagonist, on drinking behavior and renal actions of centrally administered renin. AB - Losartan, a nonpeptide angiotensin II receptor antagonist, was used to establish the role of brain AT1 angiotensin II receptor subtype on the natriuretic, antidiuretic, and dipsogenic actions of centrally administered renin. Intracerebroventricular administration of renin reduces urine volume and increases sodium excretion and water intake in conscious, male, hydrated rats. Losartan (3 or 10 mg/kg, sc) reduced the increased sodium excretion and totally inhibited the antidiuretic action induced by intracerebroventricular renin. When both renin and Losartan were given intracerebroventricularly, at the highest dose, there was a potent inhibition of the antidiuretic and natriuretic actions. Peripheral and central administration of the AT1 receptor blocker significantly lengthened the onset of drinking behavior and reduced the cumulative water intake observed after intracerebroventricular injection of renin. Our results strongly suggest that the brain AT1 receptor subtype mediates the physiologic actions of angiotensin II, such as drinking behavior, the increase in sodium excretion, and vasopressin release. PMID- 8456104 TI - Spectrophotometric measurement of plasma 2-thiobarbituric acid-reactive substances in the presence of hemoglobin and bilirubin interference. AB - The 2-thiobarbituric acid reaction with malondialdehyde has been used to assess lipid peroxidation in a variety of biologic systems. However, in an attempt to measure plasma thiobarbituric acid-reactive substances (TBARS) during extracorporeal membrane oxygenation, a form of sustained cardiopulmonary bypass, it became apparent that the absorbance signal at the 532-nm wavelength was composed not only of the peak absorbance of TBARS, but also of interfering substances from heme pigments and bilirubin. A method of subtracting interfering substances was developed and applied to normal human plasma. The method was tested by adding varying amounts of red blood cell hemolysate, bilirubin, and 1,1,3,3-tetramethoxypropane (TMP) standard to plasma and determining TBARS in the resulting mixture. In addition, varying the amount of added desferoxamine was investigated to determine the effects of iron chelation on the assay. This was important because the different samples would have varying amounts of free iron from hemoglobin to catalyze the reaction. It was found that the following equation could be used in this system to determine that amount of 532-nm absorption due to TBARS: MDA532 = 1.22[(A532) - (0.56)(A510) + (0.44)(A560)]. Regression analysis revealed an 86.6% recovery of the TMP spike. Analysis of variance showed that the variability in the model could be explained mainly by the additive increments of TMP spike (94.6%). PMID- 8456105 TI - Pregnancy-associated changes in plasma metallothionein concentration and renal cadmium accumulation in rats. AB - Pregnancy-associated changes in metallothionein (MT) concentrations in blood plasma were examined using a competitive enzyme-linked immunosorbent assay with a rabbit polyclonal antibody to rat liver MT. Plasma MT of pregnant rats significantly increased after 8 days of gestation and remained high during pregnancy and for 7 days after delivery. Gel filtration showed that both Cu and Zn were associated with the plasma MT of pregnant rats. These results suggest that plasma MT may play a role in the transport of essential metals such as Cu and Zn to fetus during pregnancy, but the source of plasma MT is unknown. Injections of cadmium chloride and cadmium-metallothionein to pregnant rats further increased the plasma MT concentrations. After injection of CdCl2, both MT and Cd concentrations in the liver of the pregnant rats were significantly lower than those of the nonpregnant rats, whereas renal Cd and MT levels were higher in pregnant rats. This increased accumulation of Cd in the kidney of pregnant rats may be related to the increase of plasma MT during pregnancy. About 5% of 6 pg of in vitro added Cd (20 pg/ml) was bound to the MT in the plasma. Therefore, Cd may be transported by the circulating MT to the kidney, leading to an increase in renal accumulation of Cd in pregnant rats. PMID- 8456106 TI - Mechanism of transport of riboflavin in rabbit intestinal brush border membrane vesicles. AB - Uptake of luminal riboflavin (RF) into the absorptive cells of rabbit small intestine was examined using purified brush border membrane vesicle (BBMV) preparations. These preparations were used in order to eliminate the interference of intracellular metabolism that occurs to the RF molecule during absorption. Uptake of RF by BBMV was found to be mainly (> 76%) the result of transport of the vitamin into the intracellular space with less binding to membrane surfaces. All 3H radioactivity that appeared in the intravesicular space after incubation with [3H]RF was found to be in the form of intact RF. Uptake of RF with time was independent of the presence or absence of a Na+ or a K+ gradient (out > in) and occurred without transaccumulation of the substrate in the intravesicular space. Furthermore, changing the incubation buffer pH showed minimal effect on RF uptake. When examined as a function of concentration, the initial rate of RF uptake was found to be saturable both in jejunal and ileal BBMV with an apparent Km of 7.24 +/- 1.06 and 8.88 +/- 0.90 microM and Vmax of 24.31 +/- 1.48 and 34.24 +/- 1.55 pmol/mg protein/5 sec, respectively. Unlabeled RF and the related compounds lumiflavin, 8-aminoriboflavin, isoriboflavin, and lumichrome all inhibited (but to different degrees) the uptake of physiologic concentration of [3H]RF. On the other hand, 8-hydroxyriboflavin, lumazine, and D-ribose all failed to inhibit [3H]RF uptake. Similarly, the membrane transport inhibitors DIDS, SITS, and furosemide all failed to inhibit [3H]RF uptake. The uptake of RF was found to be insensitive to changes in the transmembrane electrical potential, as shown by studies with anion substitution and valinomycin K(+)-induced negative or positive intravesicular potential methodologies. These results indicate that RF uptake by rabbit intestinal BBMV occurs via a carrier-mediated system that is Na+ independent in nature and transports the substrate by an electroneutral process. The role of this system in the overall absorption process of RF is discussed. PMID- 8456107 TI - Role of tyrosine kinase and phosphotyrosine phosphatase in growth of the intestinal crypt cell (IEC-6) line. AB - The roles of gastrin and sodium vanadate in proliferation were examined in cultured IEC-6 cells that are mitotically active and derived originally from jejunal crypts of the rat intestine. Incubation of the cells in the presence of gastrin at a concentration of 250 ng/ml or of sodium vanadate at a concentration of 0.2 mM leads to a 60% increase in cell growth in 24 hr. The stimulated growth in both cases was inhibited by genistein, a tyrosine kinase inhibitor. Incubation in the presence of gastrin and sodium vanadate together produced a small, albeit significant, potentiation of growth of the cells. Gastrin as well as sodium vanadate also promoted the phosphorylation on tyrosine of a similar group of proteins with molecular masses of 42, 45, 52, 60, 78, and 120 kDa. The phosphorylations were rapidly occurring as early as 5 min and lasted for only 15 min. Several proteins were detected in normal IEC-6 cells, including GTPase activating protein, raf1 kinase, phospholipase C gamma-1, and phosphoinositide 3 kinase. The results suggest that gastrin and sodium vanadate induce growth of IEC 6 cells by stimulation of tyrosine kinase and/or inhibition of tyrosine phosphatase. The gastrin and sodium vanadate effects also involve the phosphorylation of a number of proteins, the identities of which are not known at present but may include some of the kinases that are frequently associated with cell growth, such as mitogen-activated protein kinase, raf1 kinase, phosphoinositide 3-kinase, and others. PMID- 8456108 TI - Fructose utilization by the human intestinal epithelial cell line, Caco-2. AB - The potential use of Caco-2 cells as a model for the study of fructose metabolism and transport in the intestine was evaluated, since this human cell line exhibits many of the anatomical and biochemical characteristics of mature enterocytes. Pre and postconfluent cultures converted [14C]fructose to CO2, lipid, and glycogen. Apparent utilization of [14C]fructose was less than that of [14C]glucose. This difference was due in part to the more rapid uptake of glucose from medium as compared with fructose. Addition of glucose, galactose, and mannose to medium markedly decreased the metabolism, while slightly inhibiting the uptake, of [14C]fructose. These data demonstrate that fructose can serve as a carbon and energy source for Caco-2 cells, and that common dietary monosaccharides affect the efficiency of fructose metabolism. PMID- 8456109 TI - Prolactin-releasing effect of buspirone in developing and adult male and female rats. AB - The prolactin-releasing effects of buspirone, an azaspirodecanedione anxiolytic drug unrelated to the benzodiazepines in structure and pharmacologic properties, was examined in developing and adult male and female rats. The possibility that effects of this drug on hormone release could be modulated by neonatal brain sexual differentiation was also evaluated. A single injection of buspirone, 2 or 10 mg/kg body wt, increased serum prolactin (PRL) levels in both sexes; the increase was significant from Day 12 onward. The PRL-releasing effect increased with age. No significant sexual differences were observed in younger rats, but in peripubertal and adult animals, the hyperprolactinemic response was higher in the female. Neonatal androgenization of females or orchidectomy of males failed to modify the PRL-releasing action of buspirone. Serum titers of luteinizing hormone and follicle-stimulating hormone were not modified by buspirone at any age. The present results show for the first time the ontogeny of the PRL-releasing effect of buspirone in male and female rats, and provide evidence that the response is higher in the female and that the effect does not depend on brain sexual differentiation. PMID- 8456110 TI - Does dopamine inhibit or stimulate prolactin release in vitro? The effects of dopamine concentration and duration of in vivo estradiol treatment. AB - Prolactin release was examined from pituitary explants of ovariectomized, Fischer 344 rats at various times of estradiol treatment. The explants were acutely exposed to concentrations of dopamine from 0 to 10(-4) M and the concentration of prolactin in the resulting incubation medium was determined by radioimmunoassay. At 1 and 2 weeks of estradiol treatment, prolactin release from explants of Fischer 344 rats was not inhibited by 10(-6) or 10(-5) M dopamine when compared with release from explants exposed to no dopamine, whereas dopamine at doses of 10(-7) and 10(-8) M significantly stimulated prolactin release. By 3 or 4 weeks of estradiol treatment, the stimulatory effects of the low doses of dopamine were not evident and higher doses significantly inhibited prolactin release. These data indicate that dopamine can inhibit, stimulate, or produce no change in prolactin secretion and that these effects depend upon the concentration of dopamine used and the duration of estradiol treatment to which the animals are subjected. PMID- 8456111 TI - Reduced testosterone during puberty results in a midspermiogenic lesion. AB - The aim of this study was to determine the role of testosterone, as reflected in the testicular interstitial fluid, in the completion of the first wave of spermatogenesis and to further elucidate its role in spermiogenesis. At weekly intervals beginning with 26-day-old rats, body and testis weights were obtained, testicular interstitial fluid testosterone (TIF-T) was assayed, daily sperm production (DSP) was determined, and testicular tissue was structurally analyzed by light and electron microscopy. At 40 days postpartum, half the rats were treated with ethane dimethanesulphonate (EDS) to temporarily reduce Leydig cells. The other half served as controls and were treated with the vehicle. The timing of EDS treatment was just prior to the elongation of spermatids. At Day 47 (1 week after EDS treatment), TIF-T, testis weight, DSP, and number of Leydig cells were significantly reduced. At Day 54 (2 weeks after treatment), TIF-T had returned to the normal adult level, Leydig cell repopulation was apparent, and testis weight was normal. The DSP returned to normal by Day 61 (3 weeks after treatment). At 1 and 2 weeks after treatment, Step 8-9 spermatids were partially or completely detached from Sertoli cells. Results indicate that a temporary reduction of testosterone during the peripubertal period leads to a temporary reduction of the DSP approximately 1 week later. It is suggested that reduced testosterone is associated with a mid-spermiogenic lesion interfering with stable attachment of Step 8-9 spermatids to Sertoli cells during Stage VIII-IX of the spermatogenic cycle. PMID- 8456112 TI - On the apparent absence of maxi-K+ channel in rat aortic myocyte. AB - In cultured rat aortic myocytes, no high-conductance Ca(2+)-and voltage-dependent K+ channels (maxi-K+ channels) such as those found in the human and rabbit were observed. However, we have found that in freshly dissociated rat aortic myocytes, the activities of high-conductance Ca(2+)-and voltage-dependent channels were present and predominant. In cell-attached patches measured with pipettes filled with normal saline solution, their single channel conductances were 139.6 +/- 2.5 picosiemens (mean +/- SE). Under the 140-mM symmetrical K+ condition (both bath and pipette solutions contained 140 mM KCl), that measurement became 207.2 +/- 3.6 picosiemens and increased by about 50% with detaching of the membrane patch. The relative conductances of the channel to K+, NH4+, and Rb+ were 1:0.61:0.48. The conductance of these channels can readily be reduced by more than 90% by extracellularly applied 0.5 mM tetraethylammonium chloride. These characteristics show that they were maxi-K+ channels. PMID- 8456113 TI - Comparative effects of heme and metalloporphyrins on interferon-gamma-mediated pathways in monocytic cells (THP-1). AB - Previous results have demonstrated links between cell-mediated immunity, interferon (IFN)-gamma and neopterin production with heme, porphyrins, and iron metabolism. In this study, we compared the effects of heme, several metalloporphyrins, protoporphyrin IX, and iron on the signal or IFN-gamma mediated pathways, such as the expression of major histocompatibility complex class II antigens, neopterin formation, and the degradation of tryptophan. Using the human monocytic cell line, THP-1, we found that heme, Zn-mesoporphyrin, Zn deuteroporphyrin, Co-protoporphyrin, and iron reduced the efficiency of the IFN gamma signal. In addition, Zn-mesoporphyrin almost fully inhibited IFN-gamma induced degradation of tryptophan by the heme protein, indoleamine 2,3 dioxygenase. In contrast, tin-protoporphyrin enhanced the IFN-gamma effects as seen by increased neopterin production, enhanced tryptophan degradation, and elevated HLA-DR antigen expression on cells. These effects are considered to be due to the action of heme, metalloporphyrins, iron, or heme byproducts on the IFN gamma signal, rather than to direct effects on IFN-gamma-induced enzymatic pathways. Heme and metalloporphyrins were previously shown to affect heme oxygenase activity, T cell growth, and lipid peroxidation and to modulate interleukin 2 activity. These pathways are also known to be influenced by IFN gamma, and our data suggest that heme and metalloporphyrins may directly modulate the efficiency of the IFN-gamma signal. PMID- 8456115 TI - Vitamin A-enhanced cleft palate susceptibility gene maps between C4 and B144 within the H-2 complex. AB - Pregnant mice congenic with C57BL/10 in the region of H-2, the major histocompatibility complex on Chromosome 17 (B10.BR, B10.A, B10.A(1R), B10.A(2R), B10.A(15R), B10.A(18R), B10.OL, or crosses between them) were fed Purina Laboratory Chow or the same diet plus 400 IU of vitamin A daily from conception and given dexamethasone (80 or 160 mg/kg) intraperitoneally on the twelfth day of pregnancy. It was found that the added vitamin A increased the frequency of isolated cleft palate only in strains that had b alleles between C4 and B144. The enhancement of susceptibility to glucocorticosteroid-induced cleft palate by vitamin A appears to be a recessive trait and the locus, called Acp, maps centromeric to another corticosteroid-induced cleft palate gene (Dcp-2) that also is in the C4:B144 interval. PMID- 8456114 TI - Factors affecting insulin responsiveness of triglyceride synthesis in incubated chicken hepatocytes. AB - A technique was developed to isolate and incubate hepatocytes from 4-day-old chickens. Hepatocytes incubated in serum-free medium containing 1 ng chicken insulin/ml had greater rates of triglyceride (TG) synthesis than insulin unexposed cells. Greater concentrations of insulin enhanced TG synthesis. Addition to medium of a supplement containing several hormones greatly improved insulin responsiveness of TG synthesis in hepatocytes compared with cells not incubated in supplemented medium. The medium supplement did not affect TG synthesis in hepatocytes incubated in the absence of insulin. The presence, compared with the absence, of triiodothyronine in the medium supplement improved insulin responsiveness of TG synthesis. In hepatocytes incubated in supplemented medium, increasing chicken insulin concentrations augmented malic enzyme activity. Hepatocytes incubated in supplemented medium containing bovine insulin had lesser rates of TG synthesis than cells incubated with similar concentrations of chicken insulin. To determine whether insulin responsiveness of TG synthesis is affected by age of chicken, hepatocytes from 4-, 11-, and 74-day-old chickens were incubated in supplemented medium. Responsiveness of TG synthesis to chicken insulin progressively decreased in hepatocytes from older chickens. Results indicate that hepatocytes isolated from 4-day-old chickens and incubated in supplemented medium are responsive to dilute insulin concentrations and may be useful to investigate the biochemical effects of this hormone. PMID- 8456116 TI - Urinary clusterin in chronic nephrotoxicity in the rat. AB - The excretion of clusterin was compared with that of N-acetyl-beta glucosaminidase (NAG) in rats given gentamicin daily for 2 months to determine whether clusterin excretion stays elevated after NAG excretion falls during chronic gentamicin administration. Clusterin was measured by radioimmunoassay and NAG by the hydrolysis of 4-methylumbelliferyl-N-acetyl-beta-D-glucosaminide. Gentamicin at 110 mg/kg was given daily for 44 days and thereafter, at 90 mg/kg daily. The excretion rate of both proteins rose rapidly, peaked, and then declined; however, the clusterin values stayed significantly above control values for the entire study, whereas NAG values were close to normal during the last 10 days, even though tubulointerstitial disease was active at that time. For this reason, the further evaluation of clusterin as a marker of renal tubular cell injury or death is warranted. PMID- 8456117 TI - Embryonic growth inhibition induced by cocaine is associated with the suppression of ornithine decarboxylase activity. AB - Cocaine use during pregnancy results in significant increases in fetal morbidity and mortality. Multiple maternal and environmental variables influence the fetal response to cocaine, and growth suppression of the developing child is frequently associated with in utero cocaine exposure. Using intact chick embryos as well as cultured embryonic tissue as a model, we report that the growth suppression induced by cocaine exposure is correlated with molecular changes occurring directly in the embryonic cells and that these molecular changes appear to be distinct from other maternal, placental, or environmental effects of the drug, including anoxia. Specifically, embryonic cocaine exposure suppresses the normal developmental increase in ornithine decarboxylase (ODC) enzymatic activity. The loss of ODC activity during the early stages of development is dose dependent and is correlated with the degree of growth suppression. The cocaine-induced loss of decarboxylase activity is specific to ODC, but cocaine, per se, has no effect on ODC activity in vitro. Moreover, a single dose of exogenous putrescine given at 120 hr of incubation blocks the cocaine-induced growth suppression. In cultured embryonic tissue, cocaine exposure inhibits the ability of a known trophic factor (insulin) to induce growth and also blocks the associated increase in ODC activity. Preliminary data suggest that cocaine hinders the binding of insulin to embryonic cells. Because ODC is a focal enzyme for the regulation of growth, the data suggest that cocaine-induced changes in the mitogenic induction of embryonic/fetal ODC activity may be a part of the biochemical mechanism by which cocaine-induced growth inhibition occurs. PMID- 8456118 TI - Steroid hormones inhibit induction of spontaneous nitric oxide production in cultured hepatocytes without changes in arginase activity or urea production. AB - The spontaneous formation of nitrites was examined in the medium of cultured rat hepatocytes and taken as a measure of nitric oxide generation. The rate of nitrite formation increased after 8-12 hr in culture which was blocked by the addition of dexamethasone, actinomycin D, or cycloheximide. Various glucocorticoids, mineralocorticoids, and sex steroids also inhibited nitrite formation by varying degrees, without affecting arginase activity or urea production. The inhibition of nitric oxide formation appears, therefore, not to be due to changes in the availability of arginine. The results suggest that nitric-oxide synthase is induced in hepatocytes in culture and show that anti inflammatory glucocorticoids are not the only steroids that inhibit nitric oxide formation. PMID- 8456119 TI - Marginal deficiency of zinc and immunological effects. PMID- 8456120 TI - Essential and toxic trace elements in human health and disease: an update. PMID- 8456122 TI - Molecular genetics and zinc-copper interactions in human Wilson's disease and canine copper toxicosis. PMID- 8456121 TI - Regulation of human and yeast metallothionein gene transcription by heavy metal ions. PMID- 8456123 TI - Roles of zinc and copper in the nervous system. AB - Zinc deficiency in chicks and guinea pigs results in unique neurological signs, including abnormal stance and locomotion. Guinea pigs develop hypersensitivity to touch and show evidence of pain in movement. Both species exhibit decreased sciatic nerve conduction velocity. Clinical signs correlate with the peripheral neuropathy and are readily reversed by zinc therapy. Copper deficiency in second generation rats produces low dopamine levels in the corpus striatum and results in clinical signs analogous to those of Parkinson's disease. The dopamine concentration is not readily reversed by copper therapy; it correlates with striatal copper concentration, but not with liver concentration, an index of copper status. The neuropathology occurs in only part of the copper deficient population and is dam and litter related, suggesting a genetic component in addition to copper deficiency. PMID- 8456124 TI - The transport of copper. AB - In summary, one concern of copper transport is to identify the serum component(s) that deliver copper to cells. Another, to learn how copper ions penetrate cells and engage enzymes. Ceruloplasmin and albumin have received major attention as transport agents but there could be others. Copper transport operates within a system that is sensitive to copper concentrations and poised to engage copper ions should they build up to toxic levels. Uptake studies with cultured cells suggest the presence of specific membrane channels for passing copper ions and specific binding proteins that work against concentration barriers to deliver the copper internally. Diffusion, aqueous-phase pinocytosis, may also play roles in transporting copper into cells. Most work to date supports the existence of specific transporters in the membrane, yet no such carriers have been isolated or characterized outside the environment of the cell. Model system work has opened up new and intriguing ideas that link membrane potential to transmembrane transport. Studies with lower life forms have confirmed that there may be other copper transport mechanisms functional in cells. Finally, we must recognize that nearly all the copper ions in fluids and cells exists in a protein-bound form and, to a much lesser extent, as complexes with amino acids. The metal must dissociate from its protein environment to be functional. Amino acids may perform this function with albumin-bound copper. Cells, however, appear also to have membrane receptors for binding ceruloplasmin as well as mechanisms for reducing and dissociating the copper atoms bound. In this way cells are able to tap the richest excellular source of copper for metabolic purposes. We have yet to understand the finer details of that mechanism. PMID- 8456125 TI - Clinical effects of selenium deficiency. PMID- 8456126 TI - Molecular and biochemical aspects of selenium metabolism and deficiency. PMID- 8456127 TI - Regulation of iron absorption. PMID- 8456128 TI - Recent advances in the clinical and biochemical effects of chromium deficiency. AB - Signs and symptoms of Cr deficiency in the general population appear widespread due not only to suboptimal intake of dietary Cr but also the elevated consumption of simple sugars that increase Cr losses. A large percentage of the subjects with marginally impaired glucose tolerance or elevated circulating insulin respond to supplemental Cr. The mechanism of action of Cr in the potentiation of insulin activity as well as the exact structure of biologically active chromium is unclear but significant progress is being made. In summary, recent advances in chromium nutrition research strengthen the association of insufficient dietary chromium and risk factors maturity-onset diabetes and cardiovascular diseases and further document the role of chromium in the maintenance of optimal health. PMID- 8456129 TI - Free radicals and trace elements. PMID- 8456130 TI - Alterations in trace elements during brain aging and in Alzheimer's dementia. PMID- 8456131 TI - Nutritional and toxicological implication of trace elements in the immune response. PMID- 8456132 TI - Trace metals in human neurodegenerative diseases. PMID- 8456133 TI - Trace element requirements, intake and recommendations. PMID- 8456134 TI - Recent trends in analytical approaches for trace element determinations in biomedical investigations. PMID- 8456135 TI - Metallothionein in the diagnosis of zinc deficiency. PMID- 8456136 TI - Ultratrace elements of possible importance for human health: an update. PMID- 8456137 TI - Zinc, appetite regulation and eating disorders. PMID- 8456138 TI - Zinc and brain function. PMID- 8456139 TI - Zinc in developmental biology: the role of metal dependent transcription regulation. PMID- 8456140 TI - Patient classification. PMID- 8456141 TI - Evidence for use of an extension-mobilization category in acute low back syndrome: a prescriptive validation pilot study. AB - BACKGROUND AND PURPOSE: The prescriptive validity of a treatment-oriented extension-mobilization category for patients with low back syndrome (LBS) was examined. SUBJECTS: Of a total of 39 patients with LBS referred for physical therapy, 24 patients (14 male, 10 female), aged 14 to 50 years (means = 31.3, SD = 11.6), were classified as having signs and symptoms indicating treatment with an extension-mobilization approach. The remaining subjects were dismissed from the study. Patients in the extension-mobilization category were randomly assigned to either an experimental (treatment) group (n = 14) or a comparison group (n = 10). METHODS: The experimental and comparison group subjects were treated with either mobilization and extension (a treatment matched to the category) or a flexion exercise regimen (an unmatched treatment). Outcome was assessed with a modified Oswestry Low Back Pain Questionnaire administered initially and at 3 and 5 days after initiation of treatment. Data were analyzed with a 2 x 3 (treatment group x treatment period) analysis of variance. RESULTS: The subjects' rate of improvement, as indicated by the Oswestry questionnaire scores, was dependent on the treatment group to which they were assigned. Subjects treated with extension and mobilization positively responded at a faster rate than did those treated with a flexion-oriented program. CONCLUSION AND DISCUSSION: This study illustrates that a priori classification of selected patients with LBS into a treatment category of extension and mobilization and subsequently treating the patients accordingly with specified interventions can be an effective approach to conservative management of selected patients. PMID- 8456142 TI - Knee kinematics and kinetics during locomotor activities of daily living in subjects with knee arthroplasty and in healthy control subjects. AB - BACKGROUND AND PURPOSE: Knee kinematics and kinetics have not been quantitatively studied during gait, stair negotiation, and rising from a chair in the same subjects, either among healthy control subjects or among subjects with knee joint impairments. Despite this paucity of data, rehabilitation goals often include achieving a specific peak knee torque at a specific, fixed angular velocity. SUBJECTS: We compared the kinematic and kinetic performance of the knees in 15 subjects (19 knees) who had undergone knee arthroplasty (KA group) and 11 healthy subjects (22 knees) who served as a control group. The KA group subjects ranged in age from 61 to 78 years, and the control group subjects ranged in age from 26 to 88 years. The KA group subjects had had knee osteoarthritis, were > or = 1 year postsurgery, and were considered fully rehabilitated. METHODS: All subjects were analyzed during barefoot paced walking, stair ascent and descent, and arising from a chair. RESULTS: Compared with the control subjects, the KA group subjects had significantly different knee sagittal range of motion, angular velocities, and maximum knee moments during loaded knee extension. Vertical ground reactions did not differ significantly between groups. Both groups' maximum extension angular velocity exceeded 350 degrees/s during the swing phase of gait, but the maximum loaded extension velocity averaged only 140 degrees/s (during rising from a chair). Maximum knee flexion moments were approximately 10 to 15 N.m/%BW (knee moments normalized to percentage of body weight in newtons). CONCLUSION AND DISCUSSION: We concluded that locomotor ADLs demand relatively slow loaded angular velocities and low knee torques, a factor that should be considered in knee postarthroplasty exercise prescription. PMID- 8456143 TI - Predictors of physical therapy faculty job turnover. AB - BACKGROUND AND PURPOSE: The purpose of this study was to determine what factors are predictive of job turnover of faculty in physical therapy education programs. SUBJECTS: Four hundred six physical therapy faculty and 92 academic program directors participated in the study. METHODS: Data were collected from two questionnaires mailed to the participants. Fifteen predictors of turnover were tested, using correlational and multiple regression analyses for data on faculty and education programs. RESULTS: Findings showed that 10% of the faculty resigned within a 1-year period. Low, but significant, correlations were found between higher turnover and fewer years of employment, behavioral intentions to leave, lower salary, higher job stress, and baccalaureate programs. Multiple regression analysis revealed that education programs with faculty having fewer years of employment and the availability of many job alternatives demonstrated significantly higher turnover. CONCLUSION AND DISCUSSION: Measures to reduce turnover, including faculty recruitment and retention plans, job redesign strategies, and faculty development programs for new faculty, are recommended. PMID- 8456145 TI - Reliability and concurrent validity of the Metrecom for length measurements on inanimate objects. AB - BACKGROUND AND PURPOSE: The purpose of this study was to test the reliability and concurrent validity of length measurements (distance between two points) produced by a computer-interfaced, three-dimensional digitizer called the Metrecom. METHODS: A total of 344 points were marked on the surfaces of five different inanimate objects and were digitized in pairs with the Metrecom. On the first three objects, each of two testers digitized each point twice for each of two testing modes (Line Length and 3-D Digitizer); on the last two objects, only one mode (3-D Digitizer) was used. Intraclass correlation coefficients and Pearson Product-Moment Correlation Coefficients were used to assess reliability and concurrent validity, respectively. RESULTS: All of the correlation coefficients were > or = .99. In further analysis of the results, a repeated-measures, one-way analysis of variance (used with reliability data) and repeated-measures t tests (used with validity data) were used to test for differences between repeated measures. After adjustment of the alpha level for the total number of comparisons, two of the t tests for validity comparisons were significant. CONCLUSION AND DISCUSSION: The results indicate that the Metrecom provides reliable length measurements (distance between two points) on inanimate objects and that two different test modes produce consistent measurements. Further study of the validity and reliability of length measurements obtained with the Metrecom on humans under applied conditions is needed before the results of this study can be generalized to applied settings. PMID- 8456144 TI - Balance improvements in older women: effects of exercise training. AB - BACKGROUND AND PURPOSE: Loss of lower-extremity strength increases the risk of falls in older persons. The purpose of this study was to test the hypothesis that a vigorous program of lower-extremity strengthening, walking, and postural control exercises would improve the single-stance balance of healthy older women and lower their risk of falls and fall-associated injuries. SUBJECTS: From a total of 38 respondents, 21 women were randomly assigned to either a treatment group (combined training, n = 12) or a control group (flexibility training, n = 9). The subjects ranged in age from 62 to 75 years (mean = 68, SD = 3.5). METHODS: A randomized control trial compared the effects of two exercise programs on static balance. The combined training group exercised three times per week on knee extension and sitting leg press machines, walked briskly for 20 minutes, and performed postural control exercises, which included simple tai chi movements. The flexibility training group performed postural control exercises weekly. Measurements of balance were obtained on a force platform in double and single stance, at baseline and following 6 months of exercise training. RESULTS: Double stance measurements were unchanged after training. The mean displacement of the center of pressure in single stance improved 17% in the combined training group and did not change in the flexibility training group. A repeated-measures analysis of variance revealed that the difference in improvement between the combined training and flexibility training groups was not significant. DISCUSSION AND CONCLUSION: This is the first intervention trial to demonstrate improvements in single-stance postural sway in older women with exercise training. Additional studies with more subjects will be needed to determine whether a combined training program of resistance training, walking, and postural exercises can improve balance more than a program of postural control exercises alone. PMID- 8456146 TI - Between conventionality and aggression: the boundaries of passion. AB - This paper explores changes in the recent psychoanalytic theory regarding the preconditions and structural characteristics of sexual love. In briefly reviewing Freud's contributions and subsequent developments regarding infantile sexuality and the perversions, the oedipal constellation, superego development and mass psychology, a common frame is provided for the description of the love life of the sexual couple. In this context, this paper also explores how contemporary psychoanalytic formulations may help to clarify certain conflicts between conventional morality and the psychological reality of the couple in love. PMID- 8456147 TI - [Psychoanalytic geriatric psychosomatic medicine--on the origin and differential therapeutic indications of acute functional somatization in the elderly]. AB - Acute functional symptomatologies regarding elderly have thus an underestimated meaning as well for be the concerned themselves as for their surroundings and the general public. Based on outpatient or/and inpatient gerontopsychosomatic experiences of treatment with 20 patients at the age from 55 to 75 years (with an average age of 64.5 years), the author differs characteristical constellations of inner and outside reality for the elderly, which can lead to an acute functional symptomatology: 1. the activation of a psychosexual conflict which do not dependent on age 2. the conflict of being disappointed in the elderly 3. the trauma reactivation in the elderly. The differential psychogenese of those three groups is casuistically proofed and discussed from a methatheoretical point of view using the concept of nucleus conflicts (Loch 1967) and the intersection metapher of Heigl-Evers and Heigl (1984). The aim of the work is to demonstrate possibilities of gerontopsychosomatic treatment as well for massive symptomatology and to discuss the given differential indications of psychotherapy (long term analysis, analytic psychotherapy, focus therapy). PMID- 8456148 TI - [Situational effects in reporting life change events? A comparison of two assessment techniques]. AB - Studies on the role of life events in the development of malignant diseases (particularly breast cancer) often rely on so-called limited prospective designs: Women with a suspicious breast lump are interviewed prior to surgery. After having learnt the final diagnosis, the sample is divided into a group having cancer and a control group. Research using this approach was criticised for producing artifacts: knowledge of diagnosis should cause reevaluations of past events and lead to overreporting of stressful experiences. Two limited prospective studies using different assessment methodologies are compared for possible artifacts due to knowledge of diagnosis. When considering less severe events, the application of a checklist technique leads to marked memory bias as assumed above. When leaving the respondents time to reconstruct their events at length, no artifacts are present. Reporting of the severest event categories remains unaffected under both methods. PMID- 8456149 TI - [Foreign patients in psychosomatic ambulatory care]. AB - To investigate differences between the complaints of foreign and of German patients who presented at our psychosomatic outpatient department, we documented relevant social data and the results of all diagnostic interviews conducted in 1990. Of the 608 patients (100%), 542 (89.1%) were German and 66 (10.9%) of other nationalities. Foreign patients more often lived in families and more often were unemployed. They reported a higher rate of functional disturbances with a marked difference between males and females. Mental symptoms were significant rarer in foreign males. Psychoanalytic or psychodynamic treatment was more frequently recommended to German patients. Especially females of other nationalities were frequently recommended outpatient psychiatric treatment (24%) or given no treatment recommendation at all (22%). In the last section, treatment recommendations and prognostic evaluations will be discussed, taking into account the possibility of cultural subjectivity on the part of the advisers. PMID- 8456150 TI - [Eating disorder and confession. Is there a correlation between the type of eating disorder and specific religious affiliation?]. AB - At the Klinik am Korso in Bad Oeynhausen, a special center for eating disorders, 789 patients from the years 1989 and 1990 were subdivided according to their diagnosis and religious affiliation and analyzed. The most striking result was a higher incidence of anorectic abstainers among Protestants and of bulimia with vomiting among Roman Catholics. This was linked up with the more internalized drive control of the Protestants. Further investigations are encouraged to analyze the essence of this connection. PMID- 8456151 TI - Pediatric and psychiatric comorbidity. Part I: The future of consultation-liaison psychiatry. PMID- 8456152 TI - Organ transplantation psychiatry. PMID- 8456153 TI - Psychiatric aspects of heart transplantation. AB - This article, part of a series on organ transplantation, will review psychiatric aspects of heart transplantation, starting with a brief summary of medical aspects. The authors then review psychiatric symptoms and syndromes frequently encountered pre-, peri-, and posttransplantation; the selection of candidates; and treatment of psychopathology. PMID- 8456154 TI - Increased depression in multiple sclerosis patients. A meta-analysis. AB - Clinical reports and experimental studies have conflicted on depression in multiple sclerosis (MS) patients. Recent reviews show that few controlled studies have been done. A comprehensive search of the literature revealed six studies that compared depression in MS patients with depression in comparison groups. The meta-analytic combination of these studies indicates that MS patients are significantly more depressed than comparison groups. PMID- 8456155 TI - Measures of distress in 26 "environmentally ill" subjects. AB - The authors report on measures of distress in 26 subjects who had been diagnosed with environmental illness (EI) by a "clinical ecologist." EI subjects were more likely than control subjects to meet criteria for one or more personality disorder diagnoses assessed with the Structured Interview for DSM-III Personality Disorders and exhibited more somatic, mood, and anxiety symptoms assessed with the Symptom Checklist-90-R and the Illness Behavior Questionnaire. The authors conclude that subjects receiving this diagnosis may suffer from unrecognized psychological distress, which may account for some or all of the symptoms that had resulted in a diagnosis of EI. PMID- 8456156 TI - Possible immunological effects of psychotropic medication. AB - Psychoactive drugs provide an essential intervention in the care of organ transplant recipients, yet little is known of their effect on immunological function. Human and animal data on immunological effects of neuroleptic (e.g., haloperidol, phenothiazines) and antidepressant agents (e.g., tricyclic antidepressants, fluoxetine) lead to conflicting hypotheses. Lithium carbonate acts through the phosphoinositide system and has a bipolar effect on neuronal activity. Lithium is known to have immune-enhancing properties and is difficult to administer in the peritransplant period but nonetheless deserves study for possible beneficial effects on allograft function. PMID- 8456157 TI - The Transplant Evaluation Rating Scale. A revision of the psychosocial levels system for evaluating organ transplant candidates. AB - Psychosocial criteria play an important role in evaluating organ transplant candidates. The Transplant Evaluation Rating Scale (TERS) classifies patients' level of adjustment in 10 aspects of psychosocial functioning that are thought to be important in adjusting to transplantation. On the basis of pretransplant psychiatric consultations, 35 liver transplant recipients received retrospective TERS ratings. Results showed significant correlations between TERS scores and visual analogue scale ratings of five outcome variables at 1-3 years posttransplant. Significant interrater reliability was also found. The TERS represents a promising instrument for transplant candidate selection as well as a valuable tool for further research. PMID- 8456158 TI - Adverse ocular effects of anticonvulsants. AB - With increasing recognition of the interface between neurology and psychiatry, the use of anticonvulsants to treat the signs and symptoms of many psychiatric disturbances is becoming commonplace. Although rare adverse reactions, such as those in the hepatic and hematological systems, have attracted considerable concern, for many anticonvulsants it is the ocular reactions that are among the most common. This article reviews the major ocular reactions to anticonvulsants and suggests guidelines for their use. It also underscores the importance of including adverse ocular effects as part of the informed consent process. PMID- 8456159 TI - Mood, coping style, and personality functioning among adult bone marrow transplant candidates. AB - Increasing use of bone marrow transplantation (BMT) and improved survival rates have led to growing concerns regarding the psychological adjustment of BMT recipients. However, few systematic studies have been conducted and those reported have focused primarily on the psychological functioning of BMT recipients several months or years after transplantation. In this article, the authors report normative psychological data on 51 BMT candidates assessed before hospitalization. Overall, the authors found little support for previous anecdotal reports that hypothesized increased incidences of negative affect during this preadmission period. Interestingly, however, patients' use of a passive coping style was significantly correlated with higher degrees of negative affect and psychopathology. The data reported provide a foundation for a more prospective, longitudinal assessment of BMT patients. PMID- 8456160 TI - The inherent, powerful therapeutic value of a good physician-patient relationship. PMID- 8456161 TI - Postoperative mania. A case report and review of the literature. PMID- 8456162 TI - Treatment of depression with fluoxetine in corticosteroid-dependent central nervous system Sjogren's syndrome. PMID- 8456163 TI - Compulsive picking and obsessive-compulsive disorder. PMID- 8456164 TI - Organic anxiety disorder. Iatrogenic hyperthyroidism. PMID- 8456165 TI - Fluoxetine for isolated sleep paralysis. PMID- 8456166 TI - On "Catatonia on the consultation-liaison service". PMID- 8456167 TI - Amitriptyline abuse presenting as acute toxicity. PMID- 8456168 TI - Clinical and research issues in depersonalization syndrome. PMID- 8456169 TI - Bipolar and pure mania disorders precipitated by head trauma. PMID- 8456170 TI - Failure to restrain AIDS patient: RN's death sentence? PMID- 8456171 TI - Nurse $20 million judgement v. insurer reversed. Case in point: Davenport v. St. Paul Fire & Marine Ins. Co. 978 Co. (978 F. 2d 97--MS [1992]). PMID- 8456172 TI - Legal case briefs for nurses. OH: nurse anesthetists sue Board of Medicine: illegal practice of medicine issue; IN: failure to read and heed warning: "for external use only" product instilled. PMID- 8456173 TI - Patients die in hospital fire: failure to follow protocols. Case in point: Stacy v. Truman Medical Center (836 S.W. 2d 911--MO [1992]). PMID- 8456174 TI - High-frequency electrocardiogram analysis of the entire QRS in the diagnosis and assessment of coronary artery disease. PMID- 8456175 TI - Operational aspects of signal-averaged electrocardiography. PMID- 8456176 TI - Transesophageal two-dimensional echocardiography: current perspectives. PMID- 8456177 TI - Corneal and ocular surface histochemistry. AB - In summary, this review has provided information concerning the application of histochemical and cytochemical procedures used to detail the normal versus pathological cornea and ocular surface. Specifically, histochemical analysis has been used to study protein and peptide degradation in cornea, to analyze stromal non-collagenous and collagenous fibers and associated extracellular matrix. Cytochemistry of the ocular surface has been used to detail the morphology of corneal and conjunctival mucin. Use of small cationic probes as well as lectin gold binding was advantageous to quantitatively demonstrate that ocular mucin contains sialylated residues and that the number of these residues significantly changes (increases) with age. These data are important in that the degree of sialylation has been shown to correlate with the ability of bacterial organisms to adhere to and infect the immature in contrast to the mature corneal surface. The use of lectin analysis of diseased ocular tissue also has shown that there are specific alterations in glycoconjugates which occur in the diseased versus normal human cornea. Wound healing in cornea is an important problem which has been studied at length using combined histochemical and biochemical approaches. Results support the hypothesis that apical cell surfaces of the leading edge of a migrating sheet differ from those of the normal epithelium. During wound healing, alpha 6 integrin expression by corneal epithelial cells has been demonstrated, but another protein, syndecan was only seen in non-migrating epithelium which had restratified. The association of immunoglobulins with the ocular surface epithelium of the cornea, their change with age and kinetics of appearance also has been demonstrated using a cytochemical approach. Histochemical procedures have been used to localize Class I and Class II molecules in cornea and conjunctiva. Class II antigen expression has been shown to be absent on corneal endothelium, but it can be induced by treatment with IFN-gamma. These data are of importance in corneal pathology such as that resulting in rejection of corneal transplants. Langerhans cells (Class II, Ia positive) also are not found in normal central cornea. They are localized in the peripheral cornea and are stained histochemically by ADPase, ATPase and by specific anti-Ia and other antisera. Increased numbers of LC have been demonstrated in cornea following various stimuli and in diseases of the cornea including both bacterial and viral induced keratitis. PMID- 8456178 TI - Effects of contextual conditioning and unconditional stimulus presentation on performance in appetitive conditioning. AB - Four experiments with rat subjects examined the effects of contextual conditioning on conditioned appetitive performance. Experiment 1 compared the effects of contextual conditioning on performance to conditioned stimuli (CSs) with different conditioning histories. Contextual conditioning enhanced performance to the CS if the CS had first been conditioned and then extinguished, but had no effect on performance when the CS had been merely paired or unpaired with food. Experiments 2 and 3 then asked whether the effect on the extinguished CS was due to contextual conditioning acting as a cue for conditioning. In Experiment 2, extinction procedures in which extra unconditioned stimuli (USs) were presented during the intertrial intervals were found to reduce the CS's sensitivity to enhancement by contextual conditioning, but had no effect on spontaneous recovery. In Experiment 3, USs added to conditioning or extinction acquired the ability to cue the corresponding performance. Under some conditions, USs added to conditioning could suppress performance (Experiment 4). The results suggest that contextual conditioning has complex effects that can be better understood by recognizing that contextual conditioning, as well as the USs that create it, may acquire discriminative control over conditioned responding. PMID- 8456179 TI - Resident's guide to treatment of people with chronic mental illness. Committee on Psychiatry and the Community. Group for the Advancement of Psychiatry. PMID- 8456180 TI - Screening for carcinoma of the prostate: epidemiological and methodological aspects. PMID- 8456181 TI - Renal cell carcinoma with vena caval extension: operative management. PMID- 8456182 TI - Intravesical instillation therapy: alternative treatments. PMID- 8456183 TI - When should we stop intravesical treatment in patients with superficial bladder cancer? PMID- 8456184 TI - Superficial bladder cancer: primary treatment with TUR with or without laser coagulation. PMID- 8456185 TI - Immunocytology as a possible marker to identify patients who require prophylaxis. PMID- 8456187 TI - Radical cystectomy: the potential for cure and reconstruction. PMID- 8456186 TI - Image analysis DNA cytometry of bladder cancer. AB - In a retrospective analysis, the DNA histograms of 65 paraffin-embedded bladder carcinomas from radical cystectomy specimens (stage pT1-pT4a, pN0, pN1, pN2) were analyzed using an automated image analysis system (Leytas 2). Automated image analysis was able to characterize invasive bladder carcinoma as being either diploid, polyploid, or aneuploid. Within the group of aneuploid tumors, the DNA content of the stem-cell line allowed further subtyping of the tumors; hypotriploid, hypertriploid, hypertetraploid, and even hyperpentaploid tumors could be distinguished. Comparing different sites of identical tumors, the DNA histogram was found to be a stable and reproducible tumor characteristic. The various tumor types differed significantly in prognosis. This technique can also be applied to smears of urine sediment or transurethrally resected tumor chips. In the case of superficial tumors, DNA cytometry defines those tumors which are potentially invasive, requiring careful follow-up and/or early aggressive treatment. PMID- 8456188 TI - Current concepts in urinary diversion: the ileal neobladder. PMID- 8456189 TI - Neoadjuvant versus adjuvant chemotherapy in invasive bladder cancer. AB - In a disease where the majority of deaths occur from metastases, improvement in survival requires the integration of systemic therapies. Research efforts must continue to focus on improving case selection criteria, improving complete response proportions, and overcoming drug resistance. Recommending a single treatment plan such as radical surgery, chemotherapy, or radiation therapy for all patients with an invasive bladder cancer is rapidly becoming outdated. Case selection is being refined by focusing on both clinical and pathologic features of the tumor. The latter include evaluation of NM23 RNA levels, or DNA ploidy and T138 surface antigen expression, which have been shown to correlate with metastatic potential. The use of hematopoietic growth factors has the potential to improve both the tolerance of chemotherapy and complete response proportions, a prerequisite for cure. However, the dose response curves for most of the known active agents are not well defined, and ultimately, new agents and strategies will be required. Drug resistance is a major barrier, but as the mechanisms are unravelled, more selective therapies can be designed. For example, resistance to adriamycin and vinblastine, two of the agents in the M-VAC regimen are mediated in part by the mdr1 gene. Ongoing studies are attempting to identify prospectively those tumors with high levels of expression which may be more amenable to treatment with drugs that do not act through this mechanism. The main advantages of the neoadjuvant approach are the ability to perform an in vivo response evaluation and the potential for bladder preservation. In most cases additional therapy for the primary tumor is required as clinical understaging is a significant problem. For some patients, initial surgery with the definition of the prognosis on firm pathologic grounds may represent a better strategy. When this is the case, the recommendation for adjuvant treatment potentially limits therapy to a more restricted population of patients for whom therapy is essential, including, for example, patients with positive lymph nodes at the time of surgery. Ideally, these patients should be entered on clinical trials designed to assess the impact of these strategies survival. Only large scale randomized trials have the potential to minimize the heterogeneity of this patient population. PMID- 8456190 TI - Radiochemotherapy for invasive carcinoma of the bladder. PMID- 8456191 TI - Anatomic study and operative approach to retroperitoneal bilateral nerve preserving lymphadenectomy. PMID- 8456192 TI - Screening for carcinoma of the prostate in a randomly selected population. PMID- 8456193 TI - Clinical staging in carcinoma of the prostate: current aspects. PMID- 8456194 TI - Radical prostatectomy for carcinoma of the prostate: long-term results. PMID- 8456195 TI - Adjuvant therapy after radical prostatectomy. PMID- 8456196 TI - Endocrine therapy of advanced prostatic cancer. PMID- 8456197 TI - Chemotherapy of prostatic carcinoma. PMID- 8456198 TI - Organ-sparing excision of renal cell carcinoma. PMID- 8456199 TI - Imaging techniques in the diagnosis of middle ear disease. PMID- 8456200 TI - The role of lateral ear resection in managing chronic otitis externa. PMID- 8456201 TI - Otitis externa and otitis media: diagnostic and medical aspects. PMID- 8456202 TI - Total ear canal ablation and lateral bulla osteotomy for management of end-stage otitis. PMID- 8456203 TI - Ototoxicity in dogs and cats. AB - Ears are special sense organs whose principal functions are hearing and maintaining equilibrium. Aminoglycoside antibiotics, erythromycin, polymyxin B, and cisplatin can affect either or both of these functions by binding with, injuring, and/or destroying special receptor cells associated with these functions. Severe hearing loss manifests itself as deafness, whereas loss of equilibrium will present as abnormal righting reflexes, nausea, and vomiting. Damage is proportional to levels of these ototoxins in the endolymphatic fluids. Evidence suggests that toxicity may be influenced by endolymphatic calcium concentrations, and levels of cAMP and cGMP are altered in specialized cochlear cells during ototoxicity, suggesting an additional mechanism for ototoxicity. The administration of salicylates and loop diuretics may potentiate the action of ototoxins, especially aminoglycoside antibiotics, probably by increasing the levels of these toxins in the endolymphatic fluid. Although many of these assessments have been made in laboratory animals, applicability may also be expected in small domestic animals, and extreme care should be taken in prescribing potentially ototoxic drugs to small animals. Cochlear damage from ototoxic compounds occurs initially in the cells detecting high-frequency sounds located at the lower basal region. In aging dogs and humans, this sensitivity of receptors in the lower basal region is enhanced. Early auditory damage is detectable by BAER and cochlear microphonic potentials. Vestibular responses can also be detected early as vestibular ocular reflexes and visual-vestibulo-ocular reflexes. Early detection is especially important because early changes can sometimes be reversible. Cavinton (apovincaminic acid) and fosfomycin represent examples of experimental agents being evaluated in laboratory animals for application as potential treatments to limit the ototoxicity associated with various drugs. PMID- 8456204 TI - Papers from the Symposium on Statistical Methods for Evaluation of Intervention and Prevention Strategies, December 1990. PMID- 8456205 TI - Evaluation: the alpha and omega of intervention and prevention strategies. PMID- 8456206 TI - The role of NCHS data systems in the evaluation of intervention and prevention strategies. AB - Intervention and prevention strategies for the U.S.A. for the year 2000 have been broadly defined into 22 priority areas encompassing 332 health objectives. NCHS and its data systems have the major responsibility for providing the data for half of these objectives and assisting in a wide array of other data programmes both within and outside of CDC. This paper describes the process used to arrive at these objectives, highlights a few of them, and presents four examples of objectives NCHS is engaged in tracking: breast cancer mortality, breast examinations, infant mortality and cholesterol levels. PMID- 8456207 TI - An evaluation of sexual behaviour change using statistical and cognitive models. The AIDS Community Demonstration Projects. AB - We evaluate sexual behaviour change among homosexual men enrolled in the cohorts in four AIDS Community Demonstration Projects. Behaviour change is classified following the stages of behaviour change model and described using a Markov model. Predictors of behaviour change are identified and evaluated using logit models for correlated data. Sexual behaviour change within the cohort could be modelled as a first-order Markov process. In addition, predictors suggested by models of health behaviour were correlated with particular patterns of sexual behaviour change. Our evaluation revealed a variety of patterns of sexual behaviour change in the cohorts and suggests multi-faceted interventions for promotion of behaviour change. PMID- 8456208 TI - Analysis of a measles epidemic. AB - In January, February and March of 1989 an epidemic of rubeola occurred on the campus of Texas Tech University. A vaccination programme was initiated as soon as the epidemic was confirmed. Extensive case histories of all confirmed cases were collected by the Lubbock City Health Department and given an exhaustive statistical analysis by a group from the Department of Mathematics at Texas Tech University. The data and statistical analysis were used to formulate stochastic and deterministic models of the measles epidemic based on the standard SEIR model. The analysis and the simulations indicate that in order to prevent a measles outbreak on a university campus a high rate of immunity may be required (> 98 per cent). The assumptions in the models raise some interesting questions regarding social contacts which require further investigation. PMID- 8456209 TI - A bivariate survival model with modified gamma frailty for assessing the impact of interventions. AB - Bivariate survival analysis models that incorporate random effects or 'frailty' provide a useful framework for determining the effectiveness of interventions. These models are based on the notion that two paired survival times are correlated because they share a common unobserved value of a random variate from a frailty distribution. In some applications, however, investigators may have some information that characterizes pairs and thus provides information about their frailty. Alternatively, there may be an interest in assessing whether the correlation within certain types of pairs is different from the correlation within other types of pairs. In this paper, we present a method to incorporate 'pair-wise' covariate information into the dependence parameter of the bivariate survival function. We provide an example using data from the Framingham Heart Study to investigate the times until the occurrence of two events within an individual: the first detection of hypertension and the first cardiovascular disease event. We model the dependence between these two events as a function of the age of the individual at the time of enrollment into the Framingham Study. PMID- 8456210 TI - Measuring vaccine efficacy from epidemics of acute infectious agents. AB - A good measure of field vaccine efficacy should evaluate the direct protective effect of vaccination on the person who receives the vaccine. The conventional estimator for vaccine efficacy depends on population level factors that are either unrelated or indirectly related to the direct biological action of the vaccine on persons, including population structure, duration of the study, the fraction vaccinated, and herd immunity, that is, indirect effects. Indirect effects can cause the conventional vaccine efficacy estimator to be inaccurate. We review alternative vaccine efficacy estimators that control for indirect effects at the population level. Thus, they are more accurate than the conventional estimator. We use epidemic simulations to explore the robustness of the conventional and proposed estimators under different field conditions. In addition, we apply the different vaccine efficacy estimators to data from a measles epidemic in Muyinga, Burundi. PMID- 8456212 TI - Improved imputation of non-responses to mailback questionnaires. AB - Poor response rates, perhaps as low as 10 to 30 per cent, certainly bring into question the validity of any survey suffering such a malady. Repeated mailouts are capable of providing information on those persons who are resistant to responding. If one is willing to assume an exponential drop-off in response rates, then imputation is possible for the entire group of non-responders. Furthermore, a second exponential drop-off in favourable (or non-favourable) responses to particular items within the questionnaire leads to closed form estimates of population parameters and their associated standard errors. Three or more mailouts also provide a test of validity of the model assumed. PMID- 8456211 TI - Using autoregressive and random walk models to detect trends and shifts in unequally spaced tumour biomarker data. AB - Continuous time autoregressive (CAR(1)) and random walk models of time series data are provided for detecting non-random shifts and trends of tumour markers in breast cancer patients following resection for cure. The continuous time random walk model with observation error is extended to the case of multiple patient time series. These models can be used to monitor large numbers of patients with time series with few sampling events that are serially correlated and unequally spaced. Further, the methodologies can be used to recommend appropriate testing intervals. A Kalman filter recursive algorithm is used to calculate the likelihood functions arising from the CAR(1) and random walk models and to calculate recursive residuals, which are monitored by Shewhart-cusum schemes. PMID- 8456213 TI - Evaluation of protocol change in burn-care management using the Cox proportional hazards model with time-dependent covariates. AB - Survival analysis methods are valuable for detecting intervention effects because detailed information from patient records and sensitive outcome measures are used. The burn unit at a large university hospital replaced routine bathing with total body bathing using chlorhexidine gluconate for antimicrobial effect. A Cox proportional hazards model was used to analyse time from admission until either infection with Staphylococcus aureus or discharge for 155 patients, controlling for burn severity and two time-dependent covariates: days until first wound excision and days until first administration of prophylactic antibiotics. The risk of infection was 55 per cent higher in the historical control group, although not statistically significant. There was also some indication that early wound excision may be important as an infection-control measure for burn patients. PMID- 8456214 TI - An analysis of AIDS incidence data by clustering trends. AB - AIDS incidence trends vary greatly among geographic areas in the United States. We define clusters of areas within which AIDS incidence trends are similar, as areas within a cluster may have similar human immunodeficiency virus epidemic patterns and thus may lead to similar prevention/intervention strategies. Methods of exploratory data analysis are used to define such clusters from reported quarterly AIDS incidence to December 1990 (adjusted for estimated reporting delays) in homosexual and bisexual men not using intravenous drugs in 39 metropolitan statistical areas (MSAs) in the United States. After smoothing AIDS incidence in each MSA, we define groups from cluster analysis based on a measure of similarity between pairs of MSAs. A log-linear model gives estimates of the scale factors and the common trend for the MSAs in each group. Alternative metrics and simulated data suggest that the clustering is fairly robust to variations in AIDS incidence data. The resulting clusters separate MSAs with different trends, for example, MSAs in which AIDS incidence shows signs of reaching a plateau are separated from MSAs in which incidence continues to increase rapidly. PMID- 8456215 TI - The effect of matching on the power of randomized community intervention studies. AB - Currently, there is considerable interest in studies that use the community as the experimental unit. Health promotion programmes are one example. Because such activities are expensive, the number of experimental units (communities) is usually very small. Investigators often match communities on demographic variables in order to improve the power of their studies. Matching is known to improve power in certain circumstances. However, we show here that if the number of communities is small, the matched design will probably have less power than the unmatched design. This is due primarily to the loss of degrees of freedom in the matched design, which outweighs the benefits of matching on any but the strongest correlates of changes in behaviour. In the community intervention situation, even small differences in sample size between the matched and unmatched analyses can have expensive consequences. PMID- 8456216 TI - Design and analysis of studies to reduce the incidence of colon polyps. AB - Decisions regarding the design and analysis of a phase III study to reduce the incidence of colorectal polyps must take into account two complicating factors: the possibility that polyps are missed during screening exams, and variable lengths of follow-up. In this paper we investigate the effects due to misclassification on the power of statistical tests to detect a change in polyp recurrence rates. We also use Monte Carlo studies to examine the relative efficiency of different methods of adjusting for variable times of follow-up. PMID- 8456217 TI - Evaluating the effects of tubal sterilization on menstrual function: selected issues in data analysis. AB - We examined selected issues in data analysis in the Collaborative Review of Sterilization (CREST). CREST is a multicentre, prospective, observational study of women undergoing tubal sterilization. We analysed menstrual function after sterilization in over 5000 women who were enrolled in the period 1978-1983 and followed for 5 years with yearly follow-up interviews. To take into account the dependency among repeated responses from the same individuals, we used the generalized estimating equations (GEE) approach to longitudinal data analysis. Marginal modelling resulted in a statistically significant increase in the odds of menstrual dysfunction at 5 years after tubal sterilization. Transitional modelling produced rates of menstrual dysfunction given a woman's menstrual function at baseline, after adjusting for other baseline characteristics such as method of contraception before sterilization. To examine the direction of the bias that could result from non-random missing data, we refitted our models using imputed values. The models with imputed values showed the same trends as the original models. PMID- 8456218 TI - Refusal assertion versus conversational skill role-play competence: relevance to prevention of tobacco use. AB - Conversational and refusal assertion skills of 768 seventh grade youth were assessed through ratings of global (for example, effectiveness) and non-verbal (for example, eye contact) behaviour performed in two role-play scenarios. The ratings were completed after each scenario by the subjects themselves, as well as by classmate and trained adult observers. Use of the Hays and Hayashi multitrait scaling method to interpret these data revealed two results. First, the items used to measure role-play behaviour did not achieve sufficient internal consistency to create global and non-verbal composites. Second, inter-rater agreement and discriminant validity were obtained only for ratings of the global effectiveness of each of the two social skills. Next, a series of multiple regression analyses indicated that an index of the global effectiveness of refusal assertion skill, but not of conversational skill, was predictive of intention to use tobacco. Those who were relatively unskillful at refusing offers were more likely to intend to use tobacco. Analyses exploring relations of trained observer ratings of the effectiveness of both role-play types, trained observer ratings of the other global and non-verbal items, and subjects' intention to use tobacco indicated that only a hesitant voice pattern was both negatively predictive of effective refusal assertion and positively predictive of intention to use tobacco in the future. In other words, those who are hesitant when they refuse a tobacco offer are the ones most likely to report an intention to use tobacco in the future. The consistency of this last finding in the tobacco use prevention literature is discussed. PMID- 8456219 TI - Birth-weight-adjusted infant mortality in evaluations of perinatal care: towards a useful summary measure. AB - Since birth-weight-specific infant mortality rates are widely considered to be measures of the effects of perinatal medical care, birth-weight-adjusted and birth-weight-specific infant mortality rates have often been used in comparisons across hospitals and geographic areas. Wilcox and Russell have provided a model which leads to the conclusion that birth weight adjustment is biased against populations with heavier birth weights and that birth-weight-specific infant mortality rates can yield misleading results. Nevertheless, evaluators and health planners still need a summary measure of the infant mortality rate in which some sort of birth weight adjustment is used to generate an (appropriately) weighted mean of birth-weight-specific relative risks. We used the 1983-85 national linked files of live births and infant deaths to investigate two new methods that extend the Wilcox-Russell approach, 'mean adjustment' and 'Z-adjustment', to compare birth-weight-specific infant mortality rates among the white populations of the states. Colorado was used as the reference population in logistic regression analyses. Statistical interactions between state and birth weight on the conventional kilogram scale, the mean-adjusted scale, and the Z scale were examined. There were substantial interactions with birth weight on all three scales. In addition, when Colorado was used as the reference population, mean adjustment shifted the odds ratios downward to implausibly low values, especially at lower weights. The Z-adjustment method incorporating the Wilcox-Russell approach appears to be a useful alternative to birth weight adjustment. However, because birth-weight-specific mortality rates do not differ uniformly across all birth weight groups, multiple summary measures are needed. PMID- 8456220 TI - Methods for analysing county-level mortality rates. AB - The identification of counties burdened by exceptionally high rates of mortality is a fundamental step in the development of state-based intervention and prevention strategies. However, the estimation of rates from small geographic areas presents special problems, especially for rare events. This paper compares the use of crude and age-standardized rates to the use of Poisson regression models and empirical Bayes models for analysing county-level mortality rates. The results demonstrate both practical and heuristic advantages of the empirical Bayes models. Age-standardized rates adjust for differences in age structure among countries but are vulnerable to extreme variability in county age-specific rates. In our example--an analysis of diabetes mortality rates--Poisson regression did not improve the variability of estimated county-level rates. Adjusted empirical Bayes estimates dramatically shrink the observed rates while preserving some separation of the counties with extreme rates. Also, empirical Bayes estimates of rates for countries with no observed deaths are shrunk close to the prior mean. PMID- 8456221 TI - Longitudinal height velocity standards for U.S. adolescents. AB - Longitudinally based height velocity centiles for U.S. children, appropriate for paediatric clinical use, were derived for growth from ages 7 to 18 years. A series of gender- and race-specific figures present the median velocity curves for children by year of maturation. Smooth 3rd to 97th centile curves, for blacks and whites together, are provided for children who are early, average, and late maturers. The data were taken from 6532 black and white children participating in the Six Cities Study from 1974 to 1989. PMID- 8456222 TI - [What is your roentgen diagnosis? Thymoma]. PMID- 8456223 TI - [Malignant bone tumors--is amputation still necessary today?]. AB - Only one half percent of all malignant tumors are solid primary bone tumors. Early diagnosis, however, is essential, as even in the most malignant tumors (osteosarcoma and Ewing sarcoma, primarily found in adolescents) prognosis after adequate treatment is quite good. A bone tumor should be considered, when pain at an extremity is unilateral and not clearly dependent on activity, especially when it is present at night. In such cases an X-ray should be made. The diagnosis of a malignant bone tumor is always assured by biopsy. Treatment in osteosarcoma and Ewing sarcoma starts with high-dose chemotherapy over three months. After this time, a wide resection of the tumor has to be carried out. The diagnostic tools available today allow a very precise knowledge of the extent of the tumor. An amputation is, therefore, only very rarely indicated. Histologic examination of the resected tumor shows the reaction of the tumor to chemotherapy. In a good responder more than 90% of the tumor is necrotic; therefore, the chemotherapeutic treatment is continued unchanged during another nine months. In case of poor response the drug treatment is modified. Treatment follows an internationally controlled protocol. With this procedure we can expect a survival rate of 70% in osteosarcoma. Ewing sarcomas metastasize very early, but a survival rate of 50% still is realistic. Chondrosarcomas occur in an older age group. They are less malignant. Their treatment is purely surgical. For an adequate resection of chondrosarcomas and a multitude of other low-grade tumors a lot of experience is needed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8456224 TI - [Inaugural rachialgia in polyradiculoneuritis or meningoradiculitis]. AB - Meningoradiculitis or polyradiculoneuritis can manifest itself as a back pain of inflammatory nature. Two case reports give us information about the characteristics of a back pain at the onset of a neurological disease. PMID- 8456225 TI - [Blood pressure recording in outpatient service: experience with the Sandoz Pressure System]. AB - The Sandoz Pressure System (SPS) is a widely used device for ambulatory blood pressure recording. The accuracy of blood pressure profiles recorded in daily routine with this device has been demonstrated. In 34 untreated hypertensive patients the blood pressure values were in good agreement with measurements taken by auscultation. The variability of recordings was less or equal to 5 mmHg in 10% of patients for the systolic and in 94% of patients for the diastolic value. During daily activity 100 +/- 6% (mean +/- standard deviation) of the values expected by programming were available for analysis. These results confirm that arterial pressure under ambulatory conditions cannot be reliably predicted based on blood pressure measurements in the doctor's office. PMID- 8456226 TI - [Cryoglobulinemia--25-year search for an etiology]. PMID- 8456227 TI - [A case from practice (266). Binswanger encephalopathy]. PMID- 8456228 TI - Immediate early gene expression in brain during sleep deprivation: preliminary observations. AB - The two-process model of sleep regulation posits that a homeostatic drive to sleep, referred to as Process S, increases with time spent awake. The purpose of this study was to evaluate whether immediate early gene (IEG) expression increases in the brain in proportion to time spent awake, when Process S would be expected to increase. Rats were deprived of sleep by cage tapping, cage rotation and gentle handling beginning at light onset for 45 minutes, 3 hours or 6 hours. At the end of the deprivation periods, deprived animals and an equal number of controls were decapitated, the brains dissected into subregions and frozen. Northern blots were prepared from cortex, thalamus, cerebellum, pons and hypothalamus and hybridized with cDNA probes to five IEG mRNAs; c-fos, c-jun, junB, NGFI-A and NGFI-B. Basal levels of c-fos mRNA were detectable in all brain regions from all animals. Sleep-deprived animals showed higher expression of c fos mRNA than control animals following 45 minutes and 6 hours of sleep deprivation in all brain regions examined, with the greatest increases observed in the cerebellum. Surprisingly, only the pons and cerebellum showed clear increases at the 3-hour timepoint. In contrast to c-fos, c-jun mRNA was essentially invariant among the animals while junB mRNA was inconsistently elevated. The expression of NGFI-A and NGFI-B was similar to the c-fos pattern but of lesser magnitude.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8456229 TI - The 5-HT2 antagonist ritanserin decreases sleep in cats. AB - Sleep and wakefulness were recorded in cats after oral administration of the 5 HT2 antagonist ritanserin at doses of 0.5 and 1.0 mg/kg (n = 6), and after 2.5 mg/kg (n = 3). A subgroup (n = 4) of the animals also received the selective 5-HT uptake inhibitor zimeldine and a combination of ritanserin and zimeldine. The drugs were administered shortly after light onset, and sleep was recorded for 15 hours. Waking was increased and slow wave sleep (SWS), particularly deep slow wave sleep (SWS-2), was decreased throughout the recording time after ritanserin administration. Rapid eye movement (REM) sleep latency was increased, and the amount of REM sleep was reduced. In the combination study, ritanserin reduced the delayed SWS increase following the serotonin uptake inhibitor. The findings of increased waking and decreased SWS-2 after ritanserin in cats contrasts with findings from humans and rats where slow wave sleep is increased following ritanserin administration. PMID- 8456230 TI - Minute-by-minute association of heart rate variation with basal heart rate in developing infants. AB - Particular types of heart rate variation are enhanced during periods of slow heart rate and diminished when heart rate is high. We examined how the correlations between heart rate and various types of heart rate variation developed in normal infants. Polygraphic recordings were obtained from 25 infants at 1 week and at 1, 2, 3, 4 and 6 months of age. Median heart rate and the extents of heart rate variation at three distinct frequencies were determined for each 1-minute epoch. Pearson's r was used to assess the correlation of median heart rate in each epoch with each of three types of heart rate variation. For each recording, correlations were assessed separately for quiet sleep, rapid eye movement (REM) sleep and waking. The maturational patterns of heart rate by heart rate variation correlations were strongly influenced by sleep-waking state and were dissimilar to those previously reported for correlations between cardiac and respiratory measures. The findings suggest dissimilar developmental patterns for autonomic and somatic motor systems, and include a discontinuity in autonomic development at approximately 1 month of age. We speculate that these trends reflect a change in the nature of sleep states as forebrain connections develop. PMID- 8456231 TI - Bacterial meningitis--a possible complication of nasal continuous positive airway pressure therapy in a patient with obstructive sleep apnea syndrome and a mucocele. PMID- 8456232 TI - Carbamazepine in REM sleep behavior disorder. PMID- 8456233 TI - Snoring and anxiety dreams. AB - In a group of elderly males who had been exposed to excessive stress during World War II, 56% of whom suffered from current post-traumatic stress disorder, a significant association was found between snoring and the occurrence of anxiety dreams, independent of the use of sedatives, antidepressants, smoking and alcohol and coffee consumption. Anxiety dream incidence was highest when snoring was accompanied by respiratory pauses. The underlying pathophysiologic mechanisms are thought to be hypercapnia and autonomic-vegetative arousal, resulting from obstructive sleep apneic episodes in heavy snoring. Polysomnographic sleep studies are needed to confirm this hypothesis. PMID- 8456234 TI - Plasma levels of atrial natriuretic factor in moderate to severe obstructive sleep apnea syndrome. AB - To evaluate atrial natriuretic factor (ANF) secretion during sleep in obstructive sleep apnea syndrome (OSAS), plasma ANF was measured every 3 hours before and after effective nasal continuous positive airway pressure (CPAP) treatment in 10 patients with moderate to severe OSAS and 10 normal subjects. The results showed daily changes in ANF levels in normal controls and in OSAS patients after effective therapy, with a nadir at 0300 hours and a peak at 2100 hours. There was no significant daily variation of ANF levels in patients with OSAS before therapy, and ANF levels from midnight to 0900 hours were significantly higher before, as compared with after, therapy. These results indicate that OSAS patients have abnormal ANF secretion. Effective nasal CPAP therapy led to normalization of ANF secretion during sleep. PMID- 8456235 TI - Sleep in normal aging and dementia. PMID- 8456236 TI - Effect of specific muscarinic M2 receptor antagonist on carbachol induced long term REM sleep. AB - Six cats were chronically implanted with a standard set of sleep-scoring electrodes and bilateral stainless-steel guide tubes for microinjection of drugs in the peribrachial area (PBL). Pretreatment of drug injection sites in the PBL with the M2 antagonist methoctramine blocks both the immediate triggering of ponto-geniculo-occipital (PGO) waves and the later prolonged enhancement of REM sleep that is induced by carbachol. These results support the hypothesis that the carbachol effects are mediated via the M2 muscarinic receptor that is known to be present in the PBL. PMID- 8456238 TI - Bibliography of recent literature in sleep research. PMID- 8456237 TI - Untreated type 2 diabetes as a cause of daytime somnolence. PMID- 8456239 TI - [Long-term evaluation of the functional treatment of mandibular condyle fractures]. AB - Clinical and radiologic examinations were carried out after a mean 7 year follow up of functional conservative treatment of a mandibular condyle fracture in 16 patients. Anatomic and functional recovery was excellent in children and was often very good in adolescents. Signs of dysfunction were a frequent finding in adults, but these were not considered as important by the patients and their specific treatment was not required. PMID- 8456240 TI - [Osteosynthesis of the middle third of the face. A comparative analysis of screws inserted with or without preliminary tapping]. AB - Results of osteosynthesis of middle third of face were compared after insertion, with or without pre-tapping, of more than 400 miniscrews (AO, 2 mm diameter). The parameters measured were the torque, the screw/bone interface and the morphology of the implant bed. The screw/bone area of contact was large and the torque superior in the absence of pre-tapping. Greater screw retention values were also be gained by applying the miniscrews without pre-tapping in cases where bone thickness does not exceed 5 mm. Pre-tapping would appear to be indicated when the bone is thicker, to make screw insertion easier and to prevent its fracture during insertion. PMID- 8456241 TI - [Reconstruction of the mandibular symphysis using a revascularized free flap of the scapula. Surgical technic]. AB - In cases of surgically removed mandibular symphysis malignancies, the bone and mouth floor were reconstructed using osteo-musculo-cutaneous flaps. In our experience, the latter provide the best results. Removed in dorsal decubitus, they allow floor replacement. During the dissection of the tumor site, we also preserve labial and chin structures, which favours a good restoration of phonation and swallowing. PMID- 8456242 TI - [Norms, charters and standards in orthodontics]. AB - Development of numerical measurements as an expression of the diagnosis, prognosis, therapy and economics of health has resulted in the appearance of rigid standard therapeutic frameworks. Accepting these figures as objective, and not as references, could lead to the appearance of new therapeutic behaviors, with subsequent modification of the notion of medical responsibility, of patients' rights and of the possible role of Public Health Authorities. By their morphologic, psychologic, social, economic and cultural constitution, individuals are unique. It would be a serious error for treating physicians not to ensure its protection. This obligation should not be forgotten in the current evolution of health economics, reasoning of this type being applicable in all respects to the field of orthodontics. PMID- 8456243 TI - [Simulated surgery on a 3D model. Technic and applications]. AB - Treatment planning for the correction of dentofacial deformities includes prediction tracing and model surgery. However, these conventional methods provide only limited information concerning the planned spatial displacement of skeletal structures. In cases of severe deformities we add simulated 3D model surgery in an individually processed life size polyurethane skull to our work-up. The basic steps of the 3D model surgery are described, the advantages outlined and the method discussed. PMID- 8456244 TI - [Early facial rehabilitation. Apropos of 28 cases]. PMID- 8456245 TI - [Oral lichen planus and cancer. Apropos of 2 cases]. AB - Malignant changes in oral lichen planus lesions are still the subject of controversy. Two new cases provide supportive data for this thesis. Case 1: A 64 year old non smoking diabetic woman presented with combined atrophic lichen planus and erythroplasia lesions of the right buccal mucosa and a unique reticular lichen planus lesion of the left buccal mucosa. Both lesions were histologically confirmed. Despite treatment, degeneration of the Bowen's type lesion into an epidermoid carcinoma was noted within 11 months. Case 2: A 47 year old non smoking woman consulted for combined cutaneous and oral lichen planus lesions. Clinical examination showed an "acute" oral lichen planus associated with extensive ulcerative, atrophic and reticular lesions involving almost the total oral mucosa. Histology of a left buccal biopsy confirmed the diagnosis. Systemic and local corticotherapy produced marked improvement in her condition and she was not seen for five years. Follow up examination then detected a proliferative ulcerative type of epidermoid carcinoma on the left buccal mucosa. These findings appear to fulfil the clinical and histologic criteria suggestive of development of epidermoid carcinoma on a lichen planus lesion. PMID- 8456246 TI - [The use of toluidine blue in the diagnosis of neoplastic lesions of the oral cavity]. AB - Toluidine blue staining is not used extensively in the diagnosis of mucosal lesions of the buccal cavity. It is, however, an effective aid, being a diagnostic tool of choice, particularly during screening for neoplastic lesions in populations at risk. PMID- 8456247 TI - [Thrombophlebitis of the cavernous sinus of dental origin. Apropos of a case with a review of the literature]. PMID- 8456248 TI - [Osteosynthesis using micro-plates in fractures of the orbital floor]. AB - The exploration of orbital floor in case of blow-out fractures shows frequently only one or two important fragments. This fact leads us to realize osteosyntheses with titanium micro-plates in this kind of fractures. This was done for ten patients by transconjunctival approach. This technic has provided good results, clinically and radiologically. The tolerance of titanium implant was excellent. Therefore, it is unnecessary to preleve bone for grafting or to use biomaterials. Micro-plates ablation is not necessary. PMID- 8456249 TI - Effect of maxillomandibular fixation on condylar growth in juvenile Macaca mulatta: a cephalometric and histologic study. AB - The effect of maxillomandibular fixation on the growth of the mandibular condyle was studied in eight control and eight experimental male juvenile monkeys. All animals had metallic implants placed throughout the craniofacial complex in order to facilitate cephalometric analysis of growth-related changes in the maxillomandibular complex during jaw immobilization. Every 3, 6, 12, and 24 wk after insertion of the appliance two experimental animals were killed for histologic analysis. Cephalometric analysis indicated no major deviation from normal maxillary or mandibular growth in the experimental animals. The condylar growth in the experimental animals was comparable with that of the controls. Histologic analysis indicated that the articular connective tissue in experimental joints remained the same thickness as in the controls. On the postero-superior aspect of the condyle, the thickness of the prechondroblastic chondroblastic cell layer was reduced by 70-80% in the experimental animals. On the posterior aspect this cell layer was not visible after 12 wk of fixation, but was replaced by a periosteum-like, cell-rich tissue which appeared to be active in appositional formation of cancellous bone. These results indicate that long term maxillomandibular fixation does not cause major alterations in the growth of condyle or the entire mandible despite a profound decrease of the prechondroblastic-chondroblastic cell layer in the postero-superior and posterior regions of the condyle. The growth is probably due to a compensatory appositional bone formation along the surface of the condyle. It is also concluded that jaw mobility is not a prerequisite for normal maxillary or mandibular growth. PMID- 8456250 TI - Prediction of behavior-management problems in 3-year-old children. AB - The aim was to determine power of nondental background factors to predict behavior-management problems at the first dental visits of 3-yr-old children. A total of 273 children from three kinds of residential area--city, town, and rural area--in Sweden took part. The parents were interviewed before the child's dental visit. The behavior of the child was rated by registering the degree of acceptance according to the method of HOLST & CROSSNER. The following steps were rated: entering the dental treatment room, mirror in mouth, probe on fingernail and tooth, air-blower on hand and in mouth, sitting in the dental chair, and examination. The behavior was then analyzed in relation to the answers of the interviews, and a logistic regression model was used to calculate the power of the variables, separately or combined, to predict behavior-management problems. Seventy-six percent of the children cooperated well at the dental examination; 13% reacted reluctantly, and 11% reacted negatively. Two interview variables had statistically significant predictive power: the parent's expectation of a negative reaction from the child in the dental situation and the child's anxiety when meeting unfamiliar people. Sixty-nine percent of child patients accepted the examination while sitting alone in the chair. Sitting alone used as a predictor for cooperation showed sensitivity 0.80, specificity 0.71, predictive value for positive test 0.44, and predictive value for negative test 0.94. PMID- 8456251 TI - Reliability of three dental radiometers. AB - The light intensity from 80 different curing units was recorded on three dental radiometers. Even though the correlation between the recordings obtained with the three testers was rather high, some units were categorized as good units by one radiometer and poor ones by another. It was also found that, in some case, there was a pronounced difference between the output within the same type of new units. Cavities were made in extracted third molars, filled with a microfilled resin, irradiated for 40 s with 20 of the curing units, and the depth of cure was measured. The radiometers were not able to rank the 20 units in accordance with their depth of cure. We conclude that the three radiometers are not fully reliable. However, they may become very useful tools for monitoring the output from a curing unit if the radiometer and the unit are calibrated. PMID- 8456252 TI - Occurrence and distribution of blackish staining on the crowns of human teeth obtained from an archeological excavation of a medieval site in Norway. AB - An excavation in Trondheim, Norway, in 1984-85, uncovered a part of the medieval (1100-1600) cemetery of St Olav's Church. Of 388 excavated skeletons, 248 had skulls where the condition of the jaws and teeth allowed examination. In 51 of these skulls the teeth exhibited a characteristic blackish staining. A higher percentage of affected skulls was found in areas with organic, woodchip layers than in areas with gravelly sand. Affected skulls tended to have a high percentage of their teeth stained, but the staining tended to be restricted to only one or two of the three tooth surfaces scored. Posterior teeth were more often affected than anterior teeth, the occlusal/incisal part more often than the cervical part, and the buccal/labial part more often than the lingual part. Nonerupted third molars could also be stained. Staining seemed to be hampered by calculus. Occurrence of staining was independent of the presence or absence of a coffin and of coffin type. The extent of staining (% of stained surfaces within a dentition) was independent of sex and age. High correlation was found between all four jaw quadrants. There was no independence between color of the jawbone and occurrence of stained teeth. It was concluded that the staining phenomenon probably can be ascribed to factors in the soil. In vivo predisposing influences cannot be excluded. PMID- 8456253 TI - Inhibition of bovine dentin demineralization by a glutardialdehyde pretreatment: an in vitro caries study. AB - Intact bovine dentin specimens were demineralized in 25 mmol acetic acid buffers (pH 5), with and without a 5-min pretreatment with an acidic 2% glutardialdehyde (GDA) solution. The results demonstrate that GDA inhibits dentin demineralization and that the inhibition depends strongly on the initial calcium and phosphate concentration in the demineralization solution. The observed inhibition increases from about 5% without calcium and phosphate to 38% with a calcium and phosphate concentration initially of 6.4 mmol and 4.1 mmol, respectively. The inhibition can be explained either by a reduction of calcium and phosphate diffusion out of the lesion or by the retention of mineral inhibitors in the dentin. PMID- 8456254 TI - Human pulpal response to direct filling gold restorations. AB - Class V cavities were prepared in 47 caries-free premolars intended to be extracted for orthodontic reasons. A powdered gold filling material, Goldent, which can be hand condensed, was used for direct fillings. The following test groups were used: (A) cavity preparation, no filling, (B) cavity filled with Goldent only, (C) cavity lined with Tubulitec and filled with Goldent, (D) cavity with Goldent filling, sealed with IRM, and (E) positive and negative controls. The teeth were extracted after 1-200 days and the pulpal response was histologically examined. The results revealed that only in Group B, i.e. when the cavity was filled with Goldent, was the risk of a pulpal reaction obvious, although the material per se (Group D) did not influence the pulpal tissue to any serious degree. Probably the Goldent material cannot provide a marginal seal tight enough to prevent microleakage, allowing microorganisms to give rise to pulp damage and inflammation. In those cases where the cavity had been isolated with Tubulitec liner before the gold restoration was made, the pulp was effectively protected from damage caused by microorganisms. PMID- 8456255 TI - Adaptation of dental plaque to sorbitol after 3 months' exposure to chewing gum. AB - Five subjects used sorbitol-containing chewing gum for a period of 12 wk. Plaque was collected before and after the sorbitol exposure and also 12 wk after the termination of the exposure. The individual plaque samples were incubated with 14C-labeled sorbitol, and the medium was examined by HPLC. It was found that plaque samples from all subjects catabolized more sorbitol after the exposure. The flora adapted to sorbitol was persistent, and all the subjects had a higher capacity for metabolizing sorbitol even 12 wk after the end of the sorbitol exposure than before it. Formate, acetate, ethanol, and lactate were the major catabolites of sorbitol. Small amounts of succinate and propionate were found in some samples. PMID- 8456256 TI - Periodontopathic bacteria and salivary microbes before and after extraction of partly erupted third molars. AB - This study examines the effect of extraction of third molars on suspected periodontopathogenic microbes, salivary acidogenic bacteria, and yeasts. The subjects were 39 healthy conscripts aged 20.2 yr, with symptom-free, partly erupted mandibular third molars. Microbial samples were taken from the mandibular third molar pericoronal space and from the adjacent gingival pocket of the second molar. The samples were stained by Gram's and Giemsa's methods and studied under a light microscope. Stimulated saliva was collected for assessing mutans streptococci, lactobacilli, and yeast counts by chair-side kits. All partly erupted third molars were extracted from 20 test subjects; 19 control subjects were left untreated. Microbial samplings were repeated 2 and 5 months postoperatively. Results showed that at base line the total number of Gram negative bacteria, Gram-negative rods, and spirochetes was significantly higher at the third molar than at the second molar sites. The extraction of the third molars caused a significant decrease in the percentage of these bacteria at the second molar sites. High counts of salivary mutans streptococci (CFU > or = 10(6)) and lactobacilli (CFU > or = 10(5)) were also significantly less frequent after the operations. Yeast counts were not affected by the extractions. Thus, partly erupted third molars may harbor a periodontally pathogenic microflora and increase the number of salivary acidogenic microbes. PMID- 8456257 TI - Epithelial alpha-naphthyl acetate esterases in the green vervet monkey gingiva before and after periodontal surgery and during tooth eruption. AB - To provide enzymatic information on de novo formed junctional (JE) and sulcular epithelium (SE), we performed periodontal surgery on 24 teeth. Ten to 14 days postoperatively, all experimental and 16 control teeth were extracted with adjacent buccal gingiva. In addition, specimens from unerupted and partly erupted teeth containing enamel epithelium (EE) were examined. Fixed cryostat sections were cut in series, stained with HE, or incubated with and without substrate for demonstration of alpha-naphthyl acetate esterase activity and for control purposes, respectively. The distribution and intensity of the alpha-naphthyl acetate esterase activity of newly reformed JE and SE was identical to that of the original JE and SE, i.e. suprabasal and very strong. In contrast, both the oral gingival epithelium (OGE) and the EE displayed a very weak enzyme reaction. These observations indicate that the presence of alpha-naphthyl acetate activity of original and reformed JE and SE is probably site specific and of nondevelopmental origin. Heavy inflammation after healing was associated with enhanced epithelial proliferation of OGE and, in addition, marked esterase activity of these proliferations and corresponding OGE. This points at a possible inflammatory induction of the marked esterase activity seen in JE and SE as well as site-specific, connective tissue influences. Further investigation is needed to elucidate the effect of inflammation on the esterase activity. PMID- 8456258 TI - [Information and involvement in health risks exemplified by a radon survey program]. AB - As part of a large-scale radon testing program in homes for the region of the Southern Districts of the former German Democratic Republic (GDR) planned by the then West German Federal Ministry of the Environment, Natural Conservation and Reactor Safety and carried out by the Institute of Water, Soil and Air Hygiene (WaBoLu) of the West German Federal Health Office (BGA) in cooperation with the West German Federal Office for Environmental Protection (BfS) and the East German State Office for Atomic Safety (SAAS), the author (then employed at WaBoLu) was responsible for conducting the radon testing in the town of Schlema near the Czechoslovakian border in Southern Saxony. During preparatory work in this town in the fall of 1990, the author noted that the local population was very concerned about their potential radon problem. In the months previously, reports in newspapers and television had frequently pointed out the dangers to health of living in this region, often citing examples of particularly high radon levels from the area. Before the "opening" of the GDR to a free press in the fall of 1989, the local population had heard virtually nothing from the authorities about radon--neither of the possible health risk in general, nor of their own personal radon levels at home. This, together with the lack of experience of East Germans generally to evaluate critically and objectively information from the free press, had led to particularly high levels of anxiety and worry among the local population, even before radon concentrations in homes were known. In the light of these circumstances, the author decided to carry out the radon program with the help of the local school children. These children, aged 13 to 17, were entrusted with the task of carrying out the radon testing using a simple method developed by WaBoLu in all homes of the town. In class, they were informed not only about this testing method, but also about radon generally. It was hoped that, while testing in homes, the school children would pass on this knowledge to the homeowners and thus act as informal "multipliers" of correct information about radon. The approach taken is an example of how environmental hygiene and prevention-oriented environmental medicine could better handle environmental health risks that can be influenced by the individual. It is necessary to become more aware of the fact that all information intended to motivate individuals to protect themselves against environmental health risks may cause at the same time high levels of anxiety.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8456259 TI - [Evaluation of antibiotic use: a prospective study in a university hospital center]. AB - The inappropriate use of antibiotics has been documented by several studies. Most of these studies have been performed in the USA and there is very little data from Europe and Switzerland. A three-month prospective study was carried out at the University Medical Center of Lausanne in the departments of internal medicine, general surgery and traumatology. During this period, 2112 patients were hospitalized among whom 878 received one or more courses of antibiotic therapy: the treatment was given prophylactically in 35% of the cases and therapeutically in the other 65%. A total of 1165 antibiotic prescriptions were evaluated. The administration of the antibiotic was considered to be indicated in 96% of the cases. However, 24% of the prescriptions contained at least one error. 50% of the errors were observed in prophylactic treatments and most were related to the length of administration and the spectrum of the agents. The errors in therapeutic prescription were found mainly in indications for urinary and respiratory tract infections, and were related to the spectrum of the antibiotic and the length of treatment. It was calculated that the inappropriate use of antibiotics accounted for approximately 7% of the total costs of all antibiotics used. We estimated that half of this excess in costs could probably be saved by the introduction of simple corrective measures mainly directed at limiting the duration of administration. PMID- 8456260 TI - [Is there a specific response of the ECG R-wave amplitude to exercise-induced myocardial ischemia? Exercise test and dipyridamole test]. AB - Changes in electrocardiogram R-wave amplitude are often noted during treadmill stress testing. The two main reasons for this phenomenon discussed in the literature are left ventricular dimension changes and myocardial ischemia. To evaluate the relation between myocardial ischemia and electrocardiogram R-wave amplitude changes, we investigated in a retrospective study the data of 99 patients (20 females/79 males) with clinical signs of coronary artery disease. All patients had undergone exercise ECG and dipyridamole test. Electrocardiogram R-wave amplitude changes and ST-segment alterations were measured before, during and after provocation by bicycle stress test and intravenous dipyridamole. In neither test was there a specific reaction of R-wave amplitude to myocardial ischemia. During myocardial ischemia there were patients with an increase as well as a decrease R-wave amplitude. There was no significant correlation between the reaction of the R-wave amplitude in the exercise ECG when compared with the Dipyridamole test. Quantitative analysis showed a reduction of R-wave amplitude during maximum provocation in both tests, which was statistically significant in almost every subgroup of patients. In both tests the ST-segment depression was statistically significant in all groups, but there was no significant correlation between the reaction of R-wave amplitude and the ST-segment depression. In conclusion, there is no specific reaction of R-wave amplitude to myocardial ischemia. It is very unlikely, that the often noted changes in R-wave amplitude during stress testing are caused by ischemic episodes of the myocardium. Other mechanisms must be sought to explain the observed R-wave alterations. PMID- 8456261 TI - [Mechanism of coronary bypass graft disease]. AB - Clinical studies on the patency rate of different coronary bypass vessels suggest that biological properties importantly influence graft function. As regards function and patency of coronary bypass vessels, proliferative responses, antithrombotic properties, and vasomotion play important roles. Thrombotic processes are responsible for acute closure of grafts, particularly in the context of reduced endothelial function or surgical trauma to the endothelium. The internal mammary artery and gastroepiploic artery release significantly more factors with antithrombotic and antispastic properties, such as nitric oxide (the endogenous nitrovasodilator) and prostacyclin than the saphenous vein. Structural changes to bypass grafts are related to proliferation and migration of vascular smooth muscle cells. Vascular smooth muscle cells of the saphenous vein exhibit particularly pronounced proliferative responses to pulsatile stretch and platelet derived growth factor, while cells obtained from the internal mammary artery respond poorly to these stimuli. These different biological properties of the endothelium and vascular smooth muscle cells may contribute importantly to the excellent patency rate of internal mammary artery grafts, while those constructed with the saphenous vein exhibit thrombotic occlusions and proliferative changes. PMID- 8456262 TI - [Threatening thiamine deficiency in severe hyperemesis gravidarum]. AB - We report the case of a patient with severe hyperemesis gravidarum. During parenteral nutrition the patient developed threatening thiamine deficiency. Wernicke's encephalopathy and tachycardia were predominant in the clinical course. Severe lactic acidosis and prolonged prothrombin time were the leading laboratory features. Thiamine deficiency as a cause of severe metabolic acidosis or coma can be easily ruled out or validated by intravenous thiamine administration. PMID- 8456263 TI - [Laryngospasm: unusual manifestation of celiac disease]. AB - Gluten-induced enteropathy or coeliac disease is a condition characterized by malabsorption and a variety of clinical manifestations. In adults, coeliac disease may be discovered while investigating iron-deficient anemia, bone pain or unexplained weight loss. We have recently diagnosed a case of gluten-induced enteropathy in an elderly woman whose symptoms were unusual. The patient had episodes of laryngospasm secondary to severe hypocalcemia and hypomagnesemia. The malabsorption syndrome was responsible for low levels of vitamin D, causing the electrolytic imbalance. Laryngospasm is a rare symptom of hypocalcemia and has not, to our knowledge, been described in the context of coeliac disease. PMID- 8456264 TI - [Clinical course following mitral valvuloplasty]. AB - Percutaneous transvenous mitral valvuloplasty using the double-balloon technique has been attempted in 25 patients (mean age 39 +/- 10 years; 17 women, 8 men) with severe, non-calcified (20 patients) or only slightly calcified (5 patients) mitral stenosis. Valvuloplasty was successful in 22 of the 25 patients. The procedure resulted in a marked increase in mitral valve area from 1.0 +/- 0.2 to 1.9 +/- 0.5 cm2 (p < 0.001) whereas the diastolic transmitral gradient decreased from 11 +/- 4 to 4 +/- 2 mm Hg (p < 0.001). Functional classification according to the New York Heart Association improved from 2.4 +/- 0.6 to 1.7 +/- 0.5 (p < 0.001) and physical working capacity increased from 64 +/- 20 to 76 +/- 17% (p < 0.01). In 3 patients the procedure was not successful: cardiac tamponade and ventricular perforation occurred in 1 patient each and in the third valvuloplasty had to be ended because of lack of cooperation. Follow-up examination was performed 24 +/- 17 months after successful valvuloplasty. In all patients an electrocardiogram, an exercise test and an echocardiogram were obtained after 3, 12, 26 and 40 months. Sinus rhythm was found in 13 and atrial fibrillation in 9 patients before valvuloplasty. After the procedure 3 additional patients could be converted into sinus rhythm. Physical exercise capacity did not change during the follow-up. Mitral valve area determined by Doppler-echocardiography increased from 1.0 +/- 0.1 to 1.7 +/- 0.3 cm2 (p < 0.001) after valvuloplasty and decreased slightly to 1.5 +/- 0.2 cm2 (NS) during the follow-up. Left atrial chamber diameter did not change significantly after the procedure (5.2 vs. 5.0 cm). It is concluded that percutaneous mitral valvuloplasty is successful in 88% of all patients with severe, non calcified mitral stenosis. The clinical result seems to be beneficial and almost all patients had a stable follow-up for two years. Several complications during the procedure occurred in two patients (8%). PMID- 8456265 TI - [Coronary artery size in chronic mitral valve insufficiency before and following mitral valve surgery]. AB - The increase of coronary artery size in myocardial hypertrophy represents an adaptive mechanism to keep coronary blood flow normal. The relationship between coronary cross-sectional area and left ventricular muscle mass was determined angiographically in 10 patients with severe mitral regurgitation before and 28 +/ 15 months after successful mitral valve surgery. 10 subjects with atypical chest pain without coronary artery disease served as controls (C). Left ventricular muscle mass was increased preoperatively in mitral regurgitation (257 g vs C = 129 g; p < 0.001) and decreased postoperatively (205 g; p < 0.01 vs preop. and vs C). The cross-sectional area of the left coronary (= left anterior descending+left circumflex) artery was augmented preoperatively (26.5 vs C = 14.0 mm2; p < 0.001) and decreased postoperatively (22.9 mm2; p < 0.05 vs preop. and vs C). The cross-sectional area of the left coronary artery per 100 g LV muscle mass was not different in the three groups. The cross-sectional area of the right coronary artery was also increased before surgery (12.7 vs C = 8.8 mm2; p < 0.05) and decreased postoperatively (11.3 mm2; p < 0.05 vs preop. ns vs C). Our data show that in mitral regurgitation the size of the left coronary artery increases proportionally to the increase in left ventricular muscle mass. Also, the right coronary artery shows slight enlargement which is probably due to the pressure overload of the right ventricle. After surgery there is regression but not normalization of the size of the coronary arteries. PMID- 8456266 TI - [100 consecutive patients with lower gastrointestinal bleeding: causes of incorrect diagnoses, recurrent bleeding and mortality]. AB - A standard approach involving sequential investigations made it possible to identify a bleeding source in 98 out of 100 patients with massive lower gastrointestinal bleeding. In 5 cases the preoperative diagnosis was incorrect. Only in 2 patients was no pathology detectable. Recurrent bleeding occurred in 8 patients, 5 of whom subsequently died of hemorrhagic shock. The overall mortality was 10%, or 11% if a patient with late death due to massive rebleeding was included. 8 complications or deaths were due to diagnostic (n = 3) and therapeutic (n = 5) errors. The remaining complications with fatal outcome (n = 6) were due to the patient's associated or underlying disease. We conclude that in patients with angiographically visualized arteriovenous malformations in the coecum, a second lesion needs to be ruled out. To prevent some complications a more aggressive therapeutic approach seems necessary. On the other hand, there remain complications and deaths that cannot be prevented in view of the advanced stage of the associated or underlying disease. PMID- 8456267 TI - [HIV-associated Penicillium marneffei infection]. AB - We report on an HIV positive patient with a disseminated Penicillium marneffei infection. A 35-year-old Swiss homosexual male with HIV-associated immunodeficiency with a CD4 cell count of 90/mm3 presented with a two-month history of malaise, intermittent fever, loss of weight, unproductive cough and widespread molluscum contagiosum-like skin lesions, mainly on the face. The patient had travelled extensively and had last visited Thailand 19 months before admission. The chest X-ray showed bilateral diffuse reticulonodular markings. The diagnosis was suspected in bronchoalveolar lavage, which showed round-to-oval intracellular yeast cells but also elongated sausage-shaped extracellular forms. The diagnosis was confirmed on culture. Penicillium marneffei was further isolated from the following specimens: blood cultures, bone marrow, stool, skin and tracheal mucosa biopsy. Intravenous amphotericin B therapy led to a complete subsidence of all symptoms and the skin lesions healed without leaving a scar. The infection, with its clinical presentation, epidemiology, diagnostic problems and therapy is reviewed. We stress that since Penicillium marneffei is an increasingly important pathogen in HIV positive patients in Southeast Asia, this fungus can also be imported to Europe by travellers. If immunocompromised patients have molluscum contagiosum-like skin lesions, pneumonitis and a history of travelling in Southeast Asia, disseminated Penicillium marneffei infection should be considered in differential diagnosis. PMID- 8456268 TI - [Suspected adult-onset Still's disease: unexpected manifestation of leprosy]. AB - A 23-year old male from Sri Lanka was admitted to hospital with symmetrical inflammatory peripheral polyarthritis, fever of 39 degrees C and poly lymphadenopathy. At first we suspected adult onset Still's disease. The histological findings from axillary lymph node biopsy strongly suggested the diagnosis of leprosy, for which we had had little evidence thus far. Typical skin lesions were absent, skin smears were negative and neurological symptoms only became obvious much later when fever and arthritis had subsided under anti inflammatory treatment. At this time a right ulnar palsy developed, with atrophy of the interosseous muscles and thickening of the ulnar nerves at both medial epicondyles. Fite-stains of a sural nerve biopsy confirmed the diagnosis when mycobacteria were detected. Leprosy displays a clinico-pathological spectrum caused by variations in host resistance. A widely accepted classification is the five group system of Ridley and Jopling. At one extreme of this spectrum are patients with lepromatous or low resistance leprosy with numerous bacilli, and at the other those with high resistance or tuberculous leprosy where few or no bacilli are found. The numerous bacilli in the sural nerve biopsy classified the disease as lepromatous in our case. Of the various manifestations of the lepra reaction occurring in lepromatous leprosy, one is acute arthritis, but a more common one is erythema nodosum leprosum. Our patient's clinical presentation was interpreted to be a rheumatic manifestation of a type-2 reaction. This form of immunological response in leprosy is an immune complex syndrome and may mimic different rheumatic diseases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8456269 TI - [Kinetic studies of the lumbar vertebrae and the lumbosacral transition in the German shepherd dog. 2. Our personal investigations]. AB - The range and type of ventrodorsal motion between two adjacent vertebra (L3-S1) was analyzed on isolated vertebral columns of 13 German Shepherd Dogs. All except one were neurologically normal dogs. The movement from maximal flexion to maximal extension was divided into 5 degree steps. For each step, the center of motion was determined on laterolateral radiographs. It could be shown that mobility between two adjacent vertebra within the lumbar spine increases towards the lumbosacral region with the highest mobility in this joint. In the cranial portion of the lumbar spine, rotation and ventrodorsal (parallel) displacement between two adjacent vertebra was seen. Rotation dominated in the lumbosacral joint in 11 dogs, whereas parallel displacement was mainly seen in 2 dogs. Further studies on pathologic and surgically modified vertebral columns are necessary to clarify the significance of these findings in the pathogenesis of lumbosacral instability and cauda equina compression in the German Shepherd Dog. PMID- 8456270 TI - [Brucella ovis infection in rams of the "white Alp" breed. Case report]. AB - The clinical findings of seven "White Alp" rams are discussed. Six of the animals contracted Brucella ovis and exhibited signs of illness. The seventh animal indicated no Brucella ovis contact. The ejaculates of all rams showed significant changes. A spermatocele, typical for Brucella ovis, could be proven, pathologically and anatomically, in only one case. Brucella ovis was isolated from two samples. A brief discussion on the treatment of herds infected with Brucella ovis is included. PMID- 8456271 TI - [Estradiol and progesterone concentrations in the plasma of nonpregnant bitches during the sexual cycle]. AB - Measurement of the plasma concentrations of oestradiol and progesterone in six bitches on 180 consecutive days showed large fluctuations in the levels of both hormones. The concentrations of oestradiol began to increase 10-12 days before the peak levels of 38.1-89.7 pg/ml were reached, then declined again over the next 3-7 days to or below the minimum measurable value of 9 pg/ml. On the day after the maximum concentrations of oestradiol were recorded, plasma progesterone began to rise rapidly, reaching a plateau after approximately two weeks, then declining gradually after a further two weeks. At the height of the luteal phase, peak levels of 12.6-70.1 ng/ml were measured, although on some days values of less than 1 ng/ml were recorded. The time of occurrence of the initial rise in the progesterone concentration during oestrus presumably indicates that preovulatory luteinization had taken place. During anoestrus the basal concentration of progesterone was generally less than 1 ng/ml and that of oestradiol less than 9 pg/ml. The normal values derived from these observations are discussed with regard to the interpretation of oestradiol and progesterone concentrations in domestic pets under treatment in veterinary practice. PMID- 8456272 TI - [A field study of artificial insemination in horses with stallions from Ireland and mares in Switzerland]. PMID- 8456273 TI - [What is your diagnosis? Which treatment do you suggest?]. PMID- 8456274 TI - Priorities in research. PMID- 8456275 TI - Availability of Taq polymerase. PMID- 8456276 TI - Learning to save lives. PMID- 8456277 TI - Ablation of transplanted HTLV-I tax-transformed tumors in mice by antisense inhibition of NF-kappa B. PMID- 8456278 TI - Childhood vaccines: the R&D factor. PMID- 8456279 TI - Chimp colony offered for quick sale. PMID- 8456280 TI - Fallout from paper on working mothers. PMID- 8456281 TI - Old school ties: Watson, Crick, and 40 years of DNA. PMID- 8456282 TI - New marker for nerve damage. PMID- 8456283 TI - Betacellulin: a mitogen from pancreatic beta cell tumors. AB - Betacellulin, a member of the epidermal growth factor family, has been identified in the conditioned medium of cell lines derived from mouse pancreatic beta cell tumors. Betacellulin is a 32-kilodalton glycoprotein that appears to be processed from a larger transmembrane precursor by proteolytic cleavage. The carboxyl terminal domain of betacellulin has 50 percent sequence similarity with that of rat transforming growth factor alpha. Betacellulin is a potent mitogen for retinal pigment epithelial cells and vascular smooth muscle cells. PMID- 8456284 TI - Ultrastructural evidence for hair cell regeneration in the mammalian inner ear. AB - It has long been thought that hair cell loss from the inner ears of mammals is irreversible. This report presents scanning electron micrographs and thin sections of the utricles from the inner ears of guinea pigs that show that, after hair cell loss caused by treatment with the aminoglycoside gentamicin, hair cells reappeared. Four weeks after the end of treatment, a large number of cells with immature hair bundles in multiple stages of development could be identified in the utricle. Thin sections showed that lost type 1 hair cells were replaced by cells with a morphology similar to that of type 2 hair cells. These results indicate an unexpected capacity for hair cell regeneration in vivo in the mature mammalian inner ear. PMID- 8456285 TI - Regenerative proliferation in inner ear sensory epithelia from adult guinea pigs and humans. AB - Supporting cells in the vestibular sensory epithelia from the ears of mature guinea pigs and adult humans proliferate in vitro after treatments with aminoglycoside antibiotics that cause sensory hair cells to die. After 4 weeks in culture, the epithelia contained new cells with some characteristics of immature hair cells. These findings are in contrast to expectations based on previous studies, which had suggested that hair cell loss is irreversible in mammals. The loss of hair cells is responsible for hearing and balance deficits that affect millions of people. PMID- 8456286 TI - Effect of PU.1 phosphorylation on interaction with NF-EM5 and transcriptional activation. AB - PU.1 recruits the binding of a second B cell-restricted nuclear factor, NF-EM5, to a DNA site in the immunoglobulin kappa 3' enhancer. DNA binding by NF-EM5 requires a protein-protein interaction with PU.1 and specific DNA contacts. Dephosphorylated PU.1 bound to DNA but did not interact with NF-EM5. Analysis of serine-to-alanine mutations in PU.1 indicated that serine 148 (Ser148) is required for protein-protein interaction. PU.1 produced in bacteria did not interact with NF-EM5. Phosphorylation of bacterially produced PU.1 by purified casein kinase II modified it to a form that interacted with NF-EM5 and that recruited NF-EM5 to bind to DNA. Phosphopeptide analysis of bacterially produced PU.1 suggested that Ser148 is phosphorylated by casein kinase II. This site is also phosphorylated in vivo. Expression of wild-type PU.1 increased expression of a reporter construct containing the PU.1 and NF-EM5 binding sites nearly sixfold, whereas the Ser148 mutant form only weakly activated transcription. These results demonstrate that phosphorylation of PU.1 at Ser148 is necessary for interaction with NF-EM5 and suggest that this phosphorylation can regulate transcriptional activity. PMID- 8456287 TI - The Oberrothenbach catastrophe. PMID- 8456288 TI - Contamination of cDNA sequences in databases. PMID- 8456289 TI - Biotechnology in Japan. PMID- 8456290 TI - Gene therapy approval process. PMID- 8456291 TI - Genome shortcut leads to problems. PMID- 8456292 TI - Controversial vaccine shows promise. PMID- 8456293 TI - Naked DNA points way to vaccines. PMID- 8456294 TI - Immunology. Interfering with interferon. PMID- 8456295 TI - AIDS conferees get Berlin assurance. PMID- 8456296 TI - French drug developers face HIV fallout. PMID- 8456297 TI - Does E. coli have a nose? PMID- 8456298 TI - Ancient conserved regions in new gene sequences and the protein databases. AB - Sets of new gene sequences from human, nematode, and yeast were compared with each other and with a set of Escherichia coli genes in order to detect ancient evolutionarily conserved regions (ACRs) in the encoded proteins. Nearly all of the ACRs so identified were found to be homologous to sequences in the protein databases. This suggests that currently known proteins may already include representatives of most ACRs and that new sequences not similar to any database sequence are unlikely to contain ACRs. Preliminary analyses indicate that moderately expressed genes may be more likely to contain ACRs than rarely expressed genes. It is estimated that there are fewer than 900 ACRs in all. PMID- 8456299 TI - Polar location of the chemoreceptor complex in the Escherichia coli cell. AB - The eukaryotic cell exhibits compartmentalization of functions to various membrane-bound organelles and to specific domains within each membrane. The spatial distribution of the membrane chemoreceptors and associated cytoplasmic chemotaxis proteins in Escherichia coli were examined as a prototypic functional aggregate in bacterial cells. Bacterial chemotaxis involves a phospho-relay system brought about by ligand association with a membrane receptor, culminating in a switch in the direction of flagellar rotation. The transduction of the chemotaxis signal is initiated by a chemoreceptor-CheW-CheA ternary complex at the inner membrane. These ternary complexes aggregate predominantly at the cell poles. Polar localization of the cytoplasmic CheA and CheW proteins is dependent on membrane-bound chemoreceptor. Chemoreceptors are not confined to the cell poles in strains lacking both CheA and CheW. The chemoreceptor-CheW binary complex is polarly localized in the absence of CheA, whereas the chemoreceptor CheA binary complex is not confined to the cell poles in strains lacking CheW. The subcellular localization of the chemotaxis proteins may reflect a general mechanism by which the bacterial cell sequesters different regions of the cell for specialized functions. PMID- 8456300 TI - Multiple defects of immune cell function in mice with disrupted interferon-gamma genes. AB - Interferon-gamma (IFN-gamma) is a pleiotrophic cytokine with immunomodulatory effects on a variety of immune cells. Mice with a targeted disruption of the IFN gamma gene were generated. These mice developed normally and were healthy in the absence of pathogens. However, mice deficient in IFN-gamma had impaired production of macrophage antimicrobial products and reduced expression of macrophage major histocompatibility complex class II antigens. IFN-gamma deficient mice were killed by a sublethal dose of the intracellular pathogen Mycobacterium bovis. Splenocytes exhibited uncontrolled proliferation in response to mitogen and alloantigen. After a mixed lymphocyte reaction, T cell cytolytic activity was enhanced against allogeneic target cells. Resting splenic natural killer cell activity was reduced in IFN-gamma-deficient mice. Thus, IFN-gamma is essential for the function of several cell types of the murine immune system. PMID- 8456301 TI - Immune response in mice that lack the interferon-gamma receptor. AB - Interferon-gamma (IFN-gamma) exerts pleiotropic effects, including antiviral activity, stimulation of macrophages and natural killer cells, and increased expression of major histocompatibility complex antigens. Mice without the IFN gamma receptor had no overt anomalies, and their immune system appeared to develop normally. However, mutant mice had a defective natural resistance, they had increased susceptibility to infection by Listeria monocytogenes and vaccinia virus despite normal cytotoxic and T helper cell responses. Immunoglobulin isotype analysis revealed that IFN-gamma is necessary for a normal antigen specific immunoglobulin G2a response. These mutant mice offer the possibility for the further elucidation of IFN-gamma-mediated functions by transgenic cell- or tissue-specific reconstitution of a functional receptor. PMID- 8456302 TI - Heterologous protection against influenza by injection of DNA encoding a viral protein. AB - Cytotoxic T lymphocytes (CTLs) specific for conserved viral antigens can respond to different strains of virus, in contrast to antibodies, which are generally strain-specific. The generation of such CTLs in vivo usually requires endogenous expression of the antigen, as occurs in the case of virus infection. To generate a viral antigen for presentation to the immune system without the limitations of direct peptide delivery or viral vectors, plasmid DNA encoding influenza A nucleoprotein was injected into the quadriceps of BALB/c mice. This resulted in the generation of nucleoprotein-specific CTLs and protection from a subsequent challenge with a heterologous strain of influenza A virus, as measured by decreased viral lung titers, inhibition of mass loss, and increased survival. PMID- 8456303 TI - Requirement of the carboxyl terminus of a bacterial chemoreceptor for its targeted proteolysis. AB - The bacterium Caulobacter crescentus yields two different progeny at each cell division; a chemotactically competent swarmer cell and a sessile stalked cell. The chemotaxis proteins are synthesized in the predivisional cell and then partition only to the swarmer cell upon division. The chemoreceptors that were newly synthesized were located at the nascent swarmer pole of the predivisional cell, an indication that asymmetry was established prior to cell division. When the swarmer cell differentiated into a stalked cell, the chemoreceptor was specifically degraded by virtue of an amino acid sequence located at its carboxyl terminus. Thus, a temporally and spatially restricted proteolytic event was a component of this differentiation process. PMID- 8456304 TI - Requirement for Cdk2 in cytostatic factor-mediated metaphase II arrest. AB - The unfertilized eggs of vertebrates are arrested in metaphase of meiosis II because of the activity of cytostatic factor (CSF). Xenopus CSF is thought to contain the product of the Mos proto-oncogene, but other proteins synthesized during meiosis II are also required for arrest induced by CSF. In Xenopus oocytes, ablation of synthesis of cyclin-dependent kinase 2 (Cdk2) during meiosis resulted in absence of the metaphase II block, even though the Mosxe protein kinase was fully active at metaphase. Introduction of purified Cdk2 restored metaphase II arrest, and increasing the amount of Cdk2 during meiosis I (when Mosxe is present) led to metaphase arrest at meiosis I. These data indicate that metaphase arrest is a result of cooperation between a proto-oncogene kinase and a cyclin-dependent kinase and illustrate the interaction of a cell growth regulator with a cell cycle control element. PMID- 8456305 TI - Programmed cell death induced by ceramide. AB - Sphingomyelin hydrolysis and ceramide generation have been implicated in a signal transduction pathway that mediates the effects of tumor necrosis factor-alpha (TNF-alpha) and other agents on cell growth and differentiation. In many leukemic cells, TNF-alpha causes DNA fragmentation, which leads to programmed cell death (apoptosis). C2-ceramide (0.6 to 5 microM), a synthetic cell-permeable ceramide analog, induced internucleosomal DNA fragmentation, which was inhibited by zinc ion. Other amphiphilic lipids failed to induce apoptosis. The closely related C2 dihydroceramide was also ineffective, which suggests a critical role for the sphingolipid double bond. The effects of C2-ceramide on DNA fragmentation were prevented by the protein kinase C activator phorbol 12-myristate 13-acetate, which suggests the existence of two opposing intracellular pathways in the regulation of apoptosis. PMID- 8456306 TI - AIDS virus history. PMID- 8456307 TI - NIH adds an extra layer of review for sensitive grants. PMID- 8456308 TI - AIDS vaccines. MicroGeneSys withdraws from trial. PMID- 8456309 TI - Aging twins offer clues to late-onset diseases. PMID- 8456310 TI - Enzyme may blunt cocaine's action. PMID- 8456311 TI - The search for liver stem cells picks up. PMID- 8456312 TI - Protein prenylation: a mediator of protein-protein interactions. PMID- 8456313 TI - Structural relationship of bacterial RecA proteins to recombination proteins from bacteriophage T4 and yeast. AB - RecA protein is essential in eubacteria for homologous recombination and promotes the homologous pairing and strand exchange of DNA molecules in vitro. Recombination proteins with weak sequence similarity to bacterial RecA proteins have been identified in bacteriophage T4, yeast, and other higher organisms. Analysis of the primary sequence relationships of DMC1 from Saccharomyces cerevisiae and UvsX of T4 relative to the three-dimensional structure of RecA from Escherichia coli suggests that both proteins are structural homologs of bacterial RecA proteins. This analysis argues that proteins in this group are members of a single family that diverged from a common ancestor that existed prior to the divergence of prokaryotes and eukaryotes. PMID- 8456314 TI - Similarity of the yeast RAD51 filament to the bacterial RecA filament. AB - The RAD51 protein functions in the processes of DNA repair and in mitotic and meiotic genetic recombination in the yeast Saccharomyces cerevisiae. The protein has adenosine triphosphate-dependent DNA binding activities similar to those of the Escherichia coli RecA protein, and the two proteins have 30 percent sequence homology. RAD51 polymerized on double-stranded DNA to form a helical filament nearly identical in low-resolution, three-dimensional structure to that formed by RecA. Like RecA, RAD51 also appears to force DNA into a conformation of approximately a 5.1-angstrom rise per base pair and 18.6 base pairs per turn. As in other protein families, its structural conservation appears to be stronger than its sequence conservation. Both the structure of the protein polymer formed by RecA and the DNA conformation induced by RecA appear to be general properties of a class of recombination proteins found in prokaryotes as well as eukaryotes. PMID- 8456315 TI - Antibody-catalyzed degradation of cocaine. AB - Immunization with a phosphonate monoester transition-state analog of cocaine provided monoclonal antibodies capable of catalyzing the hydrolysis of the cocaine benzoyl ester group. An assay for the degradation of radiolabeled cocaine identified active enzymes. Benzoyl esterolysis yields ecgonine methyl ester and benzoic acid, fragments devoid of cocaine's stimulant activity. Passive immunization with such an artificial enzyme could provide a treatment for dependence by blunting reinforcement. PMID- 8456316 TI - Translocation of TCR alpha chains into the lumen of the endoplasmic reticulum and their degradation. AB - After synthesis, the alpha chain of the T cell antigen receptor (TCR alpha) can form a complex with other TCR chains and move to the cell surface, or TCR alpha can undergo degradation in the endoplasmic reticulum (ER) if it remains unassembled. The mechanism of translocation and degradation in the ER is unclear. It was found that the putative transmembrane region of TCR alpha (alpha tm) was incompetent on its own to act as a transmembrane region. Molecules that contained alpha tm were translocated into the ER lumen and then underwent either rapid degradation or secretion, depending on the sequence of the cytoplasmic domain. A specific signal for ER degradation within alpha tm does not appear to be present. PMID- 8456317 TI - Activity-dependent regulation of conductances in model neurons. AB - Neurons maintain their electrical activity patterns despite channel turnover, cell growth, and variable extracellular conditions. A model is presented in which maximal conductances of ionic currents depend on the intracellular concentration of calcium ions and so, indirectly, on activity. Model neurons with activity dependent maximal conductances modify their conductances to maintain a given behavior when perturbed. Moreover, neurons that are described by identical sets of equations can develop different properties in response to different patterns of presynaptic activity. PMID- 8456318 TI - An essential heparin-binding domain in the fibroblast growth factor receptor kinase. AB - Heparin or heparin-like heparan sulfate proteoglycans are obligatory for activity of the heparin-binding fibroblast growth factor (FGF) family. Heparin interacts independently of FGF ligand with a specific sequence (K18K) in one of the immunoglobulin-like loops in the extracellular domain of the FGF receptor tyrosine kinase transmembrane glycoprotein. A synthetic peptide corresponding to K18K inhibited heparin and heparin-dependent FGF binding to the receptor. K18K and an antibody to K18K were antagonists of FGF-stimulated cell growth. Point mutations of lysine residues in the K18K sequence abrogated both heparin- and ligand-binding activities of the receptor kinase. The results indicate that the FGF receptor is a ternary complex of heparan sulfate proteoglycan, tyrosine kinase transmembrane glycoprotein, and ligand. PMID- 8456319 TI - Therapy of factor VIII deficiency. AB - In spite of the numerous complications of transfusion therapy, there is no doubt that development of convenient clotting factor concentrates for home care has revolutionized the care of patients with hemophilia. With the obvious exception of HIV infections and chronic hepatitis, the majority of patients have few clinically significant adverse side effects in spite of years of replacement therapy. The development of improved viral attenuation processes may have eliminated the viral contamination of these products, but this is yet to be confirmed. The recent breakthrough in the development of highly purified, genetically engineered FVIII products will, it is hoped, eliminate all of the complications of therapy with the exception of inhibitor development. The development of recombinant FVIII replacement should ultimately lead to the availability of reasonably priced products in potentially unlimited supply. If this can be achieved, we may be able to look forward to prophylactic infusion therapy for patients with severe FVIII deficiency and eliminate the significant complications that continue to occur even with prompt treatment of hemorrhage and thrombosis. PMID- 8456320 TI - Treatment of factor VIII inhibitors: products and strategies. AB - Treatment of patients with inhibitors to FVIII remains a complex clinical problem. Although characterizing the individual patient may aid in the initial development of a care plan, no treatment is uniformly reliable for all patients. Experts in the field are as likely to disagree as agree when it comes to choosing treatment options; few randomized clinical trials exist on which to base decisions. PMID- 8456321 TI - Factor IX concentrates for clinical use. PMID- 8456322 TI - Therapy of von Willebrand disease. AB - Impressive progress has been made in the treatment of von Willebrand disease. Desmopressin is the drug of choice for mild to moderate type I von Willebrand disease patients in whom adequate hemostatic levels of vWF activity can be achieved. Cryoprecipitate from random donors is no longer an optimal choice because of the risk of transfusion-associated viral infections. In special circumstances, cryoprecipitate from a very small donor pool, particularly if obtained following desmopressin stimulation, remains an attractive alternative because these donors can be intensively screened. This therapy may also be somewhat less expensive than commercial concentrates. Virally attenuated commercial concentrates containing intact vWF multimers are currently the treatment of choice to achieve high levels of vWF for moderate to severe von Willebrand disease and for patients with variants of von Willebrand disease that cannot be adequately treated with desmopressin or for whom desmopressin is contraindicated. It is hoped that concentrates of vWF specifically designed for treatment of von Willebrand disease will prove to be safe and efficacious. Standardized assays of vWF in concentrates need to be established. Although, the optimal treatment product has not been produced, several of the more recently developed products have structures that more closely resemble intact normal plasma vWF and appear promising. PMID- 8456323 TI - Therapeutic concentrates for the treatment of congenital deficiencies of factors VII, XI, and XIII. PMID- 8456324 TI - Viral safety of clotting factor concentrates. AB - The efforts to reduce the risk of viral disease due to clotting factor concentrates have been quite successful. However, additional steps need to be taken to protect the users of these products. First, all patients should be vaccinated against hepatitis B. Second, vaccines against other viruses need to be developed. There is a great deal of interest in an HIV vaccine, and a vaccine against hepatitis C would also be a great boon to the "at risk" population. Third, more effective inactivation procedures need to be implemented in the manufacturing of concentrates other than Factor VIII, including Factor IX Complex, Coagulation Factor IX (Human), and Anti-Inhibitor Coagulant Complex. Despite the advances that have been made, it should be remembered that none of these procedures is perfect and the risk will never be reduced to zero. This is because the plasma pools will always contain infectious virus and the manufacturing process, regardless of how carefully controlled, cannot be made fail-safe. Errors will be made that result in contamination or inadequate treatment of products. For this reason, strict adherence to standard operating procedures and good manufacturing practices is essential. The investments of time, money, and hard work that have been made toward improving the safety of clotting factor concentrates have yielded a handsome return thus far. It is hoped that continued efforts in this direction will result in even greater benefits. PMID- 8456326 TI - Clotting factor concentrates in clinical practice. Standardization and assay. PMID- 8456325 TI - Recombinant blood clotting proteins for hemophilia therapy. PMID- 8456327 TI - Reassessing priorities: identifying the determinants of HIV transmission. PMID- 8456328 TI - Developing a primary health care management information system that supports the pursuit of equity, effectiveness and affordability. AB - A key set of goals of primary health care (PHC) includes equity, effectiveness and affordability. By equity, we mean universal coverage and care according to need; by effectiveness, that the system has a favorable impact on mortality and serious morbidity; by affordability, that the system is within the budgetary reach of government and communities. There are other requirements of PHC as well: that the system be socially and culturally acceptable, and that communities are active participants in the development and implementation of the system. Further, the PHC system should be compatible with larger system of a region or country, and possibly serve as a prototype for the development of larger health systems. With these requirements in mind, the Aga Khan University has developed a series of community-based, urban PHC systems, each serving a population of about 10,000, in the katchi abadis (squatter settlements) of Karachi. These communities are severely deprived, with high infant, child and maternal mortality rates. The PHC systems are designed to achieve equity, effectiveness and affordability, and within 3-5 years have advanced substantially toward those goals. A key factor in those developments has been the management information system (MIS), which has served as a basis for planning, managing and evaluating the PHC systems. Central questions about such an MIS are: What kind of MIS design is necessary to support the pursuit of those goals? What problems arise in the MIS as such a system is implemented? What kinds of changes and adaptations need to be considered in the MIS as the PHC system itself matures? What does the PHC system cost, and what part of the total cost of the PHC system is attributable to the MIS? How practical is this kind of MIS, developed in small prototype PHC systems, for replicability in larger health systems? What are the possibilities and requirements for simplification in order to be used in health systems that are less intensively managed? The experience of AKU in Pakistan in the development of PHC systems, with associated management information systems, helps to answer these questions. PMID- 8456329 TI - Minorities and mental health. AB - It is argued that minority status, despite some recent evidence to the contrary, is a risk factor for mental ill-health. The evidence reviewed suggests that it is the experience at the local, rather than national, level that is critical. The effect appears to be due to the reduced exposure to prejudice and increased social support that a consonant group offers. The effect cannot be readily explained in terms of social selection. PMID- 8456330 TI - White liver: a cultural disorder resembling AIDS. AB - Hoodoo is a folk belief system common among black Americans. Conjuration and rootwork are other terms used to describe this system which includes the casting of spells and witchcraft. This paper describes the black folk concept of 'white liver', an aspect of hoodoo which bears striking resemblance to AIDS. White liver refers to a condition characterized by sexual excess and a wasting to death of sexual partners. Although clearly antedating by many years the current AIDS epidemic, white liver is important as a contemporary black cultural entity that may be used to describe AIDS or to articulate a fear of AIDS. PMID- 8456331 TI - Attitudes towards disabilities in a multicultural society. AB - Health practitioners (N = 665) from the Chinese, Italian, German, Greek, Arabic and Anglo Australian communities used social distance scales to rate the attitudes of people in their communities toward 20 disability groups. Significant differences were found in community attitudes toward people with 19 of these disabilities. Overall the German community expressed greatest acceptance of people with disabilities, followed by the Anglo, Italian, Chinese, Greek and Arabic groups. However the relative degree of stigma attached to the various disabilities by the communities was very similar. In all communities, people with asthma, diabetes, heart disease and arthritis were the most, and people with AIDS, mental retardation, psychiatric illness and cerebral palsy, the least accepted of the disability groups. These stigma hierarchies were remarkably similar to other hierarchies reported over the last 23 years. The findings have important implications for people with disabilities and health practitioners in multicultural societies. PMID- 8456332 TI - Primary mental health care in Nicaragua. AB - Thirty-nine primary health care workers were interviewed in the Esteli Region of Nicaragua to determine their knowledge, attitudes and ideas for change regarding mental illness in primary care. The aim was to provide a qualitative description in order to assess learners' needs and plan a training programme in mental health care to be carried out by the Esteli mental health team. The results showed a wide range in knowledge regarding diagnoses and treatments. Many of the workers were keen to learn more and nearly all had positive ideas as to how primary care and links with secondary care could be improved. The study is an example of how a small qualitative study can help planning of training programmes and can highlight those primary health care issues relevant to the local situation. PMID- 8456333 TI - Predictors of psychological distress among southeast Asian refugees. AB - This paper analyzed data from one of the first needs assessment projects on a representative non-clinical population of Southeast Asian refugees in the United States in order to test two hypotheses: (1) whether or not premigration experiences still have an effect on psychological distress beyond the initial resettlement period and (2) whether or not interethnic group differences existed in the predictors of psychological distress between three Southeast Asian refugee groups, the Vietnamese, Cambodians and Lao. The results of the analysis of 2180 subjects supported both hypotheses. Regardless of ethnicity and the number of years in the U.S., premigration trauma events and refugee camp experiences were significant predictors of psychological distress even 5 years or more after migration and significant group differences in the types of postmigration distress predictors were also found. Acculturation concerns for the Vietnamese and Lao were influenced by both premigration and postmigration variables. In contrast, the primary concerns of the Cambodians were still related to premigration issues. The results also indicated that Vietnamese and Lao women were more likely to experience distress than their male counterparts, but no gender differences emerged for the Cambodians. Age predicted distress for Vietnamese and Cambodians, but not Lao. Similar to previous findings in the literature, Cambodians reported the highest levels of distress, followed by Lao and then Vietnamese. Interpretations of these results for this community sample are proposed. PMID- 8456334 TI - Changes in life satisfaction over a two and a half year period among very elderly people living in London. AB - Research evidence concerning the contributions of social networks and support to the subjective wellbeing (i.e. life satisfaction) of older persons is not consistent. This paper reports the results of an investigation of the effects life satisfaction at baseline, social network type and health status, on life satisfaction at follow-up at two and a half years later among people ages 85+ living in the East end of London. The percentage of the total variation in overall life satisfaction which was explained by the model was 47%. Baseline life satisfaction score explained most of this (43%), and the remaining variation was explained largely by functional status and age. Previous analyses of baseline life satisfaction reported that health and functional status had accounted for most of the variation between groups, far more than social network and support variables. PMID- 8456335 TI - Professional constructions of a 'lay' illness: 'nerves' in a rural 'coloured' community in South Africa. AB - As part of a larger study, medical practitioners working in Mamre, a 'coloured' village close to Cape Town, South Africa, were interviewed concerning their use of the term 'nerves' in interaction with their patients. Contrary to the initial perception of researchers and some clinicians, the term is not simply a folk category. It does, however, represent a medium through which psychosocial issues are discussed in the clinical encounter. Differences in the usage of the term by different practitioners seemed to indicate different attitudes towards patient care. The data are presented and discussed in the context of debates concerning the development of more accessible and responsive health services in a future South Africa, and the information gleaned has implications for future training of clinicians. PMID- 8456336 TI - Evaluation of a face-to-face weaning food intervention in Kwara State, Nigeria: knowledge, trial, and adoption of a home-prepared weaning food. AB - This paper reports on the evaluation of a pilot intervention which used nutrition education techniques to introduce a fortified, home-prepared weaning food (eko ilera, or 'pap for health') in 12 communities in Kwara State, Nigeria, from June to August, 1988. The recipe added toasted cowpea flour, red palm oil, and sugar to increase the energy and protein density of the traditional maize or sorghum starch porridge used for weaning from 38 to 85 kcal and 0.8 to 2.0 g protein per 100 g. A stratified, random sample of participating (n = 295) and non participating (n = 301) mothers from the same communities were interviewed from 2 to 8 weeks following the completion of the intervention, and their rates of knowledge, trail, and adoption of eko ilera were evaluated. Of the participating mothers, 57% (95% CI: 51%, 63%) knew the modified recipe, 48% (43%, 54%) tried it, and 17% (12%, 21%) adopted it with the intention of using it in the future. Only 2% (1%, 7%) of non-participating mothers knew about the recipe. Multivariate analyses indicated that the mothers' level of education and their perception of the cost and length of preparation time of the recipe were significantly associated with its adoption. The intervention was successful in using face-to face nutrition education methods to introduce eko ilera to mothers in this region of Nigeria and to encourage its trial and adoption. PMID- 8456337 TI - Blood is hotter than water: popular use of hot and cold in Kel Tamasheq illness management. AB - Ethnographic data on Malian Kel Tamasheq use of hot-cold classification in illness management within the household show that, although hot and cold vocabulary is known by most people, the concepts of opposition and balance are only one of several approaches to treating illness and are rarely used in practice. This differs from the importance ascribed to hot and cold by Tamasheq traditional healer specialists as cited in the literature. The logic of the classification is based on symptoms rather than foods, and is associated with the presence or absence of blood or water. Many people are able to reproduce this symptomatic logic without being able to articulate its details. Because of their more frequent contact with blood through menstruation and childbirth, women are more susceptible to cold symptoms which are most frequently and clearly articulated in relation to gynaecological illnesses. Knowledge and understanding of the classification varies by social class, with those groups more recently assimilated into the Tamasheq population less likely to subscribe to this interpretation of illness. The influence of data collection methodology to the apparent importance of hot and cold as an explanatory system is also discussed. PMID- 8456338 TI - Comparing nurses' and patients' pain evaluations: a study of hospitalized patients in Kuwait. AB - All eligible patients hospitalized on the general medical, surgical and pediatric wards of a district hospital in Kuwait during the first 2 weeks of April 1990 (N = 199) were interviewed about their pain and the medical care provided. Patients rated their current pain using a 0-10 visual analogue scale (VAS) on which 0 was labelled 'no pain' and 10 'unbearable pain', and also the least and worst levels of pain which they had experienced during the previous 24 hr. Pediatric patients rated their mood at these times using a cartoon faces scale ([1]: McGrath P.A., DeVeber L. L. and Hearn M. T. Advances in Pain Research and Therapy, pp. 387-393. Raven Press, New York, 1985). Patients were asked to describe the most painful procedure which they had experienced whilst hospitalized, to detail their reactions to any uncontrolled pain, and recount the outcome of any requests made for additional analgesics. Whichever nurse on duty had had prime responsibility for caring for the patient was asked to furnish comparable VAS ratings of the patient's pain, and to categorize the patient as providing an accurate picture of, exaggerating, or understating his/her pain. Overall, nurses returned significantly lower pain estimates than their patients. Pediatric patients and patients described by their nurses as 'understating their pain', however, were exceptions. The vast majority of patients approved of the medical care provided and the pain management, and considered that nurses are well able to judge patients' pain and are concerned about what pain patients experience. And yet the VAS reports from patients indicated that uncontrolled pain was common. Also, when specifically questioned, a substantial proportion of patients stated that pain had had a negative impact on their mood and activity. Various explanations for these findings are discussed, and their implications for effective pain management. Some of the special problems facing nurses in Kuwait are considered. PMID- 8456339 TI - Validity and reliability testing of the FAMCARE Scale: measuring family satisfaction with advanced cancer care. AB - The purpose of the study was to test the validity and reliability of the FAMCARE Scale which was developed to measure family satisfaction with advanced cancer care. The FAMCARE Scale was developed based upon earlier qualitative research which identified indicators of family care satisfaction and a subsequent Q-sort study that reduced those items to the most salient indicators of satisfaction according to a larger, representative sample (N = 210). A pilot test of the FAMCARE Scale using a convenience sample of 30 family members of advanced cancer patients was conducted. The scale achieved internal consistency estimates of 0.93 at two testing times, a test-retest correlation of 0.91, and estimates of criterion validity using the McCusker Scale of 0.80 and 0.77. Cluster analysis of the scale suggested 4 subdimensions. Although the scale requires further testing to establish its reliability and validity, these preliminary results indicate that the scale may be a psychometrically sound instrument useful for measurement of family satisfaction with advanced cancer care. PMID- 8456340 TI - The impact of induced abortions on fertility in Israel. AB - The impact of induced abortions on fertility in Israel is considered, bearing in mind that this is the country with the highest fertility rate in the developed world. The public health point of view is examined and from the data collected it seems that most of the efforts to prevent abortions, not based on medical grounds, should concentrate on young women and the newly married. PMID- 8456341 TI - The expectation of life without disability in England and Wales. PMID- 8456342 TI - From explosions to black lung: a history of efforts to control coal mine dust. AB - Highlights in the history of efforts to prevent occupational lung disease among coal miners in the United States are reviewed. The Federal Coal Mine Health and Safety Act of 1969 is summarized, and the sources and effects of its provisions to prevent coal workers' pneumoconiosis are examined. Descriptions follow of the identification of coal workers' pneumoconiosis as a disease, identification of respirable coal mine dust as its cause, and establishment and enforcement of an exposure limit. The development of prevention efforts focusing on surveillance of both exposure and outcome and of enforcement of dust control methods is examined. PMID- 8456343 TI - Recent developments in coal mining technology and their impact on miners' health. AB - Advances in technology have significantly reduced the long-term health risks associated with underground coal mining. While the potential risks include exposure to hazardous substances and noise, the reduction of respirable dust in the workplace has been emphasized here because of the greater probability of exposure and the well-documented consequences. Since enactment of the Mine Health and Safety Act of 1969, great strides have been made in reducing worker exposure to respirable dust. As production rates continue to increase, particularly in longwall sections, continued advances in dust control technology will be required. These advances will be needed to meet existing, and perhaps even more stringent future, exposure limits. Mechanization has resulted in a significant reduction in exposure to hazards while increasing productivity. Use of remotely controlled equipment is also increasing rapidly, and efforts are underway to develop completely automated mining systems. These automated systems may further reduce the risk of health impairment due to the underground working environment. PMID- 8456344 TI - Chest radiography in dust-exposed miners: promise and problems, potential and imperfections. AB - Since the early 1900s, it was recognized that many dust-exposed workers developed abnormal radiographs during life. Chest radiography remains the primary means of determining the presence and extent of dust-induced pneumoconiosis, although it is ineffective for detecting airways obstructions from mine dust exposure. This chapter reviews the uses and limitations of chest radiography in the study, surveillance, screening, clinical diagnosis, and disability determinations of occupational lung diseases in dust-exposed workers. PMID- 8456345 TI - Respiratory protection in the mining industry. AB - Because respirators may have adverse effects on an individual, it is important that the occupational physician understand these effects and appropriate respirator use in the mining industry. Few studies have been performed on the effects of respirator wear among workers who may have some physiologic impairment. This chapter reviews the relevant regulations, types of respirators used in the mining industry, and the various effects of their use, as well as provides reasonable guidelines for determining fitness to wear these devices. PMID- 8456346 TI - Injuries in the mining industry. AB - This chapter reviews the history, statistics, and epidemiology of mining injuries in the United States. Although injuries in mining have been drastically reduced since the start of this century, their rates have not changed substantially in the past decade, and mining injury rates remain among the highest of all US industries. The injuries are often severe, as indicated by both high fatality rates and the high average number of days lost from work for nonfatal injury. Cumulative trauma disorders and acute traumatic injuries are common. PMID- 8456347 TI - Clinical aspects of coal workers' pneumoconiosis and silicosis. AB - Coal workers' pneumoconiosis and silicosis are two important respiratory disorders that result from the inhalation of respirable particles in mining. This chapter focuses on the clinical aspects of these disorders, including their pathogenesis and pathology, and approaches to their evaluation and management. PMID- 8456348 TI - Strategies for the treatment of pneumoconiosis. AB - Regulatory control of dust in the workplace has greatly reduced the development of pneumoconiosis, yet the prevention of silicosis and coal workers' pneumoconiosis has not been accomplished. Cases of pneumoconiosis continue to occur, and there is no proven way to affect the natural history of these progressive inflammatory and fibrotic processes. Although pneumoconiosis and silicosis are considered untreatable in Western countries, in China an aggressive search has been underway for therapeutic agents and clinical procedures to treat these diseases. The important aspects are reviewed for the tried therapies, including corticosteroids, aluminum citrate complex, PVNO, tetrandrine, xinin, and whole lung lavage. PMID- 8456349 TI - Respiratory health risks among nonmetal miners. AB - The risks of occupational respiratory disease faced by nonmetal miners are the focus of this review. An understanding of the respiratory risks requires an understanding of the minerology of the ground and rock around the materials being mined. Relevant exposures encompass radon gas and deisel fumes, as well as mineral and rock dusts, including free silica. The types of materials mined and their associated health effects are examined, including the silicates (fibrous silicates such as asbestos, asbestiform fibrous minerals such as wollastonite and fuller's earth, and nonfibrous silicates such as talc and kaolin), sedimentary precipitates such as phosphates, potash, gypsum, and salt, as well as hydrocarbon containing sedimentary rock such as oil shale. PMID- 8456350 TI - Legal aspects of impairment and disability in pneumoconiosis. AB - This chapter analyzes and explains the meanings, under the federal Black Lung program, of the terms impairment, disability, and pneumoconiosis. To accomplish this objective, this chapter reviews the regulations and administrative and judicial decisions made under the Black Lung Act, and for comparison, it refers to definitions given to, or applications made of, those terms in other jurisdictions and programs. PMID- 8456351 TI - Problems in monitoring dust levels within mines. AB - The collection of dust samples in mines is a multifaceted problem. Initially, one must define the situation being sampled and the purpose of the sampling in order to establish an appropriate sampling plan, including specification of the type of mining process (surface vs. underground, metal vs. nonmetal vs. coal) as well as the mining system employed (equipment). The next step is to decide the nature of the hazard being monitored (i.e., dust depositing in alveolar air spaces entails use of respirable dust sampling, upper airways entails thoracic-fraction sampler, and systemic effects call for an inhalable-fraction sampler) in order to select the appropriate sampler. Deciding on a particular sampling strategy is a complex issue involving federal regulations as well as compliance. PMID- 8456352 TI - The management of unexpected findings at surgery. AB - The improved accuracy of noninvasive scanning devices has led to a decrease in unexpected findings. Nevertheless, the surgeon still may encounter unsuspected diseases during abdominal exploration. A logical approach to these problems is outlined in this article. PMID- 8456353 TI - Anesthetic problems. Venous air embolism, airway difficulties, and massive transfusion. AB - Perioperative anesthetic complications require the coordinated efforts of both the surgical and anesthesia teams. These complications, or their sequelae, have significant influence on the care of the patient in the preoperative, intraoperative, and postoperative periods. PMID- 8456354 TI - Intraoperative fluid management. AB - The surgeon should be cognizant of both the intraoperative and postoperative consequences of intraoperative fluid administration. Optimal fluid management should take into consideration the patient's overall condition and should not be based solely on the cardiovascular response to volume loading. The selection of a particular fluid for resuscitation solution should be tailored to the patient's individual situation. No single fluid preparation will be appropriate for all clinical situations. Crystalloids, colloids, and hypertonic saline solutions have all been shown to be effective in restoring intravascular volume. Each has its own relative advantages and disadvantages and will be appropriate in differing situations. Colloid preparations should not be avoided for fear of inducing pulmonary edema, and the use of hypertonic solutions should not be precluded by fear of potential metabolic complications. The judicious use of both hypertonic solutions and colloids is safe. For the vast majority of routine surgical cases, where the patient is hemodynamically stable and postoperative fluid overloading is not a significant problem, isotonic crystalloids such as lactated Ringer's are both sufficient and cost effective. PMID- 8456355 TI - Management of the difficult abdominal closure. AB - Hemorrhagic shock and multiple trunk injuries, especially severe pelvic fracture, may cause massive swelling of intra-abdominal viscera and the abdominal wall, thereby precluding safe, primary abdominal wall closure. Primary closure, under tension in such patients, causes a multitude of problems including respiratory compromise, reduced cardiac output, oliguria, enterocutaneous fistulae, impaired abdominal wall nutrient blood supply, necrotizing fasciitis, evisceration, and death of the patient. Multiple methods have been described to aid the surgeon in circumventing these problems. The authors advocate the abdominal wall pack technique, which has the advantages of ease of implementation and a low rate of wound complications. PMID- 8456356 TI - Use of the pulmonary artery catheter to reduce operative complications. AB - Despite several prospective, randomized trials that demonstrated reductions in operative morbidity and mortality rates, routine use of invasive monitoring has not achieved widespread acceptance. This probably comes from skepticism about the validity of some of the studies along with known complications of the pulmonary artery catheter. The major studies are reviewed and a rational approach to monitoring is presented. PMID- 8456357 TI - Complications of laparoscopic surgery. AB - The potential complications of a laparoscopic procedure include those related to laparoscopy and those related to the specific operative procedure. The majority of these complications occur during the early learning phase for laparoscopy. They also may occur, however, during procedures performed by surgeons who have considerable laparoscopic experience. As new applications for laparoscopy continue to emerge, it is important for the surgeon to be familiar with the possible complications associated with the various laparoscopic procedures. Only through an appreciation of the potential complications of a procedure can their overall incidence be reduced to a minimum. PMID- 8456358 TI - Empiric antibiotic therapy of abdominal sepsis and serious perioperative infections. AB - This article discusses empiric therapy for several serious infections in surgical patients. The accepted antibiotic treatment for purulent peritonitis, the empiric treatment of postsurgical wound infection, and the empiric treatment of postsurgical pneumonia are discussed. The cost of the various regimens is listed. Recommendation of the various regimens is based on the seriousness of the infection, peculiarities of the hospital flora, effectiveness of the regimens, and cost. PMID- 8456359 TI - Complications of surgery of the thyroid and parathyroid glands. AB - Surgery of the thyroid and parathyroid glands can be performed safely in the majority of patients. The greatest risk for postoperative morbidity arises from injury to the laryngeal nerves or the parathyroid glands. A sound knowledge of regional anatomy combined with an unhurried, meticulous operative technique are essential if injury to these structures is to be avoided. PMID- 8456360 TI - Complications of vascular surgery. AB - Hemorrhage, early thrombosis of a graft or vessel nerve injury, graft infection, and renal failure are frustrating problems for vascular surgeons. All frequently arise from technical complications. Methods of avoiding these problems are discussed. PMID- 8456361 TI - Major hepatic trauma. AB - The intraoperative management of complex liver injuries can be extremely challenging. During the past two decades, there have been some changes in philosophy regarding the optimal techniques for controlling hemorrhage and decreasing mortality and morbidity rates. An overview of these techniques is presented. PMID- 8456362 TI - Differential diagnosis and management of unexplained bleeding. AB - A brief overview of normal hemostasis is reviewed. Congenital and acquired causes of bleeding are discussed. Methods for evaluation of the coagulation system of the patient prior to an operative procedure are outlined. A strategy for characterizing intraoperative bleeding disorders and appropriate interventions are discussed. PMID- 8456363 TI - New techniques in burn wound management. AB - The critical care management of the burn patient has advanced such that those patients with larger burned surface areas are surviving for longer periods. Wound management and closure thus become critical to the patient's ultimate outcome. New techniques for modifying the extent of the burn injury and for replacing the skin cover are described in this article. PMID- 8456364 TI - Surgical issues in the management of the HIV-infected patient. AB - As of 1992, approximately 1,000,000 Americans are infected with HIV. The natural history of the illness includes a relatively long latent period (about 10 years) between infection and development of AIDS. Surgeons are called on to participate in the management of these patients, usually for diagnostic biopsies, supportive measures, or intraabdominal events. Precautions and safe surgical practices will minimize the risk of HIV transmission from patient to surgeon (or surgeon to patient). PMID- 8456365 TI - Pericardioscopy and biopsy. AB - The diagnosis of malignant pericardial effusion is usually made by pericardial fluid cytology or open pericardial biopsy. A case is reported where diagnostic difficulty warranted flexible pericardioscopy under fluoroscopic guidance. The technique is described. PMID- 8456366 TI - Technical aspects of endoscopic removal of benign tumors of the esophagus. AB - We describe the technique of thoracoscopic removal of benign tumors of the esophagus. The technical problems of this new approach are described in the context of our initial experience of four cases. PMID- 8456367 TI - A rapid and simple technique for insertion of a T-tube into the minimally incised common bile duct at laparoscopic surgery. AB - We fabricated a stainless-steel over-tube for rapid and simple insertion of a T tube following common bile duct exploration during laparoscopic surgery. With this over-tube, operating time is greatly shortened because minimal incision and only two sutures are needed to prevent bile leakage. PMID- 8456368 TI - Specialized endoscopic equipment. PMID- 8456370 TI - Endosurgical training methods: is it surgical training that is out of control? PMID- 8456369 TI - Surgery 2001. A technologic framework for the future. PMID- 8456371 TI - Reflections on surgical training. PMID- 8456372 TI - Fluorescein-assisted laparoscopy in the identification of arterial mesenteric ischemia. AB - Accurate identification of acute mesenteric ischemia remains a challenge. It was hypothesized that fluorescein-assisted laparoscopy (FAL) may have a role in the identification of acute arterial mesenteric ischemia. Arterial ischemic small bowel segments were prepared in 11 dogs. Following 2.5 h of ischemia, laparoscopy was performed with a standard light source followed by FAL with an argon laser. These two techniques were immediately compared with open inspection. Standard laparoscopy correctly identified 10 ischemic segments. FAL correctly identified 9 ischemic segments and the combination of the 2 techniques allowed laparoscopy to correctly identify all 11 ischemic segments. Standard laparotomy with and without fluorescein correctly identified 10 ischemic segments. The difference between laparoscopy and laparotomy was not significant (P > 0.6, Fisher's exact test). The combination of laparoscopic evaluation with and without fluorescein allowed identification of small-bowel ischemia in all subjects in this canine model. Further studies are warranted to delineate the accuracy of laparoscopy in other patterns of mesenteric insufficiency before clinical application. PMID- 8456373 TI - Bile duct complications after laparoscopic cholecystectomy. AB - A retrospective review and analysis of patients referred to the Division of Gastroenterology and the Section of Gastrointestinal Surgery with common bile duct complications after laparoscopic cholecystectomy was undertaken in order to identify injury patterns, management, and outcome. Sixteen patients were identified over a 20-month period. Twelve patients had major common bile duct injuries and four had minor injuries (cystic duct leaks). Seventy-one percent of injuries occurred with surgeons who had done more than 13 laparoscopic cholecystectomies. Eighty-three percent of patients who had major ductal injury did not have a cholangiogram prior to the injury. Sixteen percent of patients with major common bile duct injuries had findings of acute cholecystitis and 58% of these major injuries were "easy" gallbladders. One-third of major injuries were recognized at operation. Two-thirds of immediate repairs failed. All cystic duct leaks were managed nonoperatively. It appears that bile duct complications after laparoscopic cholecystectomy are more common in the community than is reported. Bile duct complications occur with surgeons who are experienced and inexperienced with laparoscopic cholecystectomy. Common bile duct injuries, unrecognized at laparoscopic cholecystectomy in the majority of cases, usually occur with "easy" gallbladders. Operative cholangiography is not utilized in the majority of common bile duct injuries. When immediate repair of common bile duct injuries is undertaken, the majority are unsuccessful. Endoscopic retrograde cholangiopancreatography (ERCP) is invaluable in the diagnosis and management of bile duct complications. Cystic duct leaks may be managed successfully with endoscopic stents. PMID- 8456374 TI - Intraoperative colonoscopy. AB - From 1987 to 1991, we performed intraoperative colonoscopy on 66 patients as a result of the following indications: the air leakage test (53%), detection of a previous malignant polypectomy site (20%), inability to complete preoperative colonoscopy (17%), detection of the source of intestinal bleeding (4%), and detection of impalpable colonic lesions (4%). Intraoperative colonoscopy was successful in 61/66 patients and provided information that altered the planned operation in 10 of 61 completely examined patients. The air leakage test proved useful in detecting subclinical anastomotic leaks. The indications for intraoperative colonoscopy have been expanded, and this procedure is often useful when one is attempting to decide on the appropriate surgical strategy for patients. PMID- 8456375 TI - Laparoscopic repair of small bowel and colon. A report of 26 cases. AB - This is a retrospective review of laparoscopic repair for enterotomies created during therapeutic or diagnostic laparoscopy in 26 women. All patients had mechanical and antibiotic bowel preparation preoperatively. The indication for operative laparoscopy was endometriosis (18), severe abdominal adhesive disease (7), and adhesions with Crohn's disease (1). Enterotomies were secondary either to CO2 laser vaporization or excision of endometriosis and/or lysis of adhesions (23) and trocar insertion (3). The injuries included small-bowel enterotomies (9), colotomies (4), and rectotomies (13). No clinical complications related to enterotomy repair were noted. Twenty-three patients were discharged 1 day after surgery; one was discharged on postoperative day 2; and two were discharged on postoperative day 3. We concluded that small- and large-bowel enterotomies can be repaired safely via the laparoscope with minimum morbidity in patients with prepared bowel. PMID- 8456376 TI - Two-step endoscopic resection of gastric leiomyomas. AB - Our two-step technique for endoscopic treatment of gastric leiomyomas is illustrated. From January 1979 to June 1991, nine symptomatic patients with sessile leiomyomas of the stomach were treated at the Endoscopy Division of Istituto Nazionale Tumori, Milan. The diagnosis was achieved by means of endoscopic observation of the lesion and, when possible, by ultrasound endoscopy. This new technique consists of first removing superficial portion of the tumor by electrosurgical snare. Second, a cleavage plane is found within the proper muscle layer; the tumor is enucleated as much as possible by tightening the snare around it and creating a pseudo-stalk. No major complication occurred nor were any recurrences observed at 21.8 months in the 7/9 patients treated by endoscopy alone. Endoscopic therapy was performed on an outpatient basis and only large lesions required short hospitalization. PMID- 8456377 TI - Training for minimally invasive surgery. Need for surgical skills. AB - Controversy exists regarding the training of surgeons for the performance of minimally invasive surgical procedures. The use of live animals is essential, especially in teaching dissection techniques. Seventeen percent of animals experienced excessive operative hemorrhage, which contributed to premature mortality during training exercises, demonstrating the need for live animals in this component of the training. A number of abdominal procedures can be performed with minimally invasive techniques without suturing by utilizing a rapidly expanding array of devices. However, other procedures cannot be successfully accomplished without suturing skills. Laparoscopic suturing skills are particularly demanding; thus specific training and practice prior to hands-on exercises in animal models is recommended. Emphasis on acquisition of advanced laparoscopic surgical skills is a necessity. PMID- 8456379 TI - Cognitive recovery correlates with white-matter restitution after head injury. AB - Longitudinal measurements of local cerebral perfusion (LCBF) and local partition coefficients (L lambda) using xenon-enhanced computed tomography were examined in six patients who had suffered from head injury at a mean age of 30 +/- 9.3 years. They were selected from a larger group with head injury because all were observed longitudinally to make excellent cognitive recovery some years after acute cerebral trauma. Results were compared with similar longitudinal measurements made in six age-matched neurologically normal volunteers. In the index group, cognitive test scores were reduced at the time of the first LCBP measurement but significantly improved to normal at the time of the second. The mean interval between measurements was 2.7 +/- 0.7 years. At the time of the first measurement, all six patients exhibited abnormal volumes of white matter with reduced Hounsfield numbers and LCBF and L lambda values. Abnormalities in volume of white matter and LCBF and L lambda values improved to normal at the time of the second measurement. Perfusion values for frontal cortex, putamen, and thalamus were still slightly reduced but also improved toward normal between measurements. Cognitive recovery correlated best with restoration of white matter integrity, suggesting that following head injury, cognitive impairments may be associated with temporary disconnections of corticothalamic projection systems. PMID- 8456378 TI - Colonoscopic indirect lymphangiography in a canine model. AB - Colorectal malignancies metastasize most frequently to mesenteric lymph nodes. Preoperative staging of these nodes by current modalities is problematic. This study evaluates the feasibility of indirect mesenteric lymphangiography as a colonoscopic technique in a canine model. Ten mongrel dogs underwent endoscopic submucosal injection of Ethiodol at various sites in the transverse, descending, and rectosigmoid areas. Serial abdominal roentgenograms were obtained up to 2 weeks postinjection. In seven of the animals, demonstration of mesenteric nodal uptake corresponding to the area(s) of injection was radiographically documented. In the remaining animals (early in the series) nodal opacification was inadequate. This lack of nodal uptake appeared to be due to nonsubmucosal contrast injection. No complications were noted. Colonoscopic indirect lymphangiography appears to be a safe and potentially useful modality in the evaluation of mesocolonic lymph nodes. Further studies to refine this technique and investigate its potential to preoperatively delineate abnormal nodal architecture are warranted. PMID- 8456380 TI - Balloon occlusion of a spontaneous carotid-cavernous fistula in Ehlers-Danlos syndrome type IV. AB - A case of spontaneous carotid-cavernous fistula associated with Ehlers-Danlos syndrome Type IV was treated successfully by transarterial balloon embolization. To minimize the stress to the arterial wall, we detached three silastic balloons with low-attachment force in the cavernous sinus with the aid of a proximal balloon to control the high flow of the fistula. To achieve complete obliteration, we had to inflate the third balloon to dimensions that occluded the cavernous portion of the internal carotid artery. Patients with Ehlers-Danlos syndrome Type IV carry a high risk when undergoing any diagnostic or therapeutic endovascular procedure due to the fragility of their blood vessels. Recognition of this entity is important and special attention should be paid to its pathophysiology for a successful treatment. PMID- 8456381 TI - Intracranial fibromyxoma in a four-year-old child. AB - A case of an intracerebral fibromyxoma in a 4-year-old female with a developing left hemiplegia is described. Primary intracranial benign fibrous tumors are rare. A review of the relevant patients in the literature revealed 12 other cases. The management of this patient and an analysis of reported cases are presented. PMID- 8456382 TI - A high-position basilar top aneurysm approached via third ventricle: case report. AB - The authors report a subfrontal transventricular approach to a high-position basilar top aneurysm considered to be inaccessible by conventional pterional or subtemporal techniques. This special technique may be preferred in the case where a megadolichobasilar artery coexists with such an aneurysm as it has the advantage of protecting the brain from the detrimental effects of strong retraction. PMID- 8456383 TI - Primary papillary meningioma of the optic nerve sheath: a case of unique location and benign pathology. AB - I report here a case of primary papillary meningioma of the optic nerve sheath which developed in the left eye of a 54-year-old woman over a period of 20 years. A review of 123 primary papillary meningiomas, including the current instance, disclosed that they tended to occur in young patients of both sexes at an average age of 35 years, with one-fourth of them occurring in the first two decades of life, and with a female/male ratio of 3:2. These meningiomas were most frequent in the supratentorial compartment of the cranial cavity, especially on the cerebral convexity and in the parasagittal region. They were uncommon subtentorially, intraspinally, and outside the central nervous system. Most reported papillary meningiomas were claimed to be malignant, but the tumor of this particular woman was benign pathologically and clinically. PMID- 8456384 TI - Blade-deviated fenestrated clips for anterior communicating artery aneurysms. AB - Blade-deviated fenestrated clips developed by one of the authors were applied very successfully in 15 cases of A Com A aneurysms which corresponded to 32% of the aneurysms upon which were operated. Of the 15, 13 cases were projected superiorly, which is the most difficult and hazardous type if ruptured at the neck. The characteristic feature of the clip is the lateral deviation of occluding blades. The superiorly projecting type A Com A aneurysm is located posterolateral to the A Com A in the operative field, and the clips were extremely useful in the aneurysms in providing safer and more exact occlusion via parallel closure of the A Com A or the aneurysm neck. PMID- 8456385 TI - Shunted hydrocephalus: normal upright ICP by CSF gravity-flow control. A clinical study in young adults. AB - Hydrocephalic patients with years of ventricle shunts may be disabled by shunt overdrainage. Gravity-induced upright CSF shunt flow produces this overdrainage with abnormally low, upright ICP. Consequently, the concept of a normal level of zero ICP, which ventricle shunts must mimic, was developed. For 4.5 years, this concept has been applied in hydrocephalus patients by using a Siphon Control Device as a Zero Pressure Device in ventricle shunts. The results in 56 patients, including 42 overdrainage problems, were assessed by clinical grading, ICP record analyses, and computed tomographic (CT) ventricle size comparisons. All patients ultimately achieved satisfactory clinical results. This occurred in 80% of the patients on the first insertion. Adjustment of the vertical level of the Zero Pressure Device was necessary in 20%. The optimum clinical result correlated with an upright ICP of -66 mm of H2O. This postoperative ICP correlated within 4 mm of the Zero Pressure Device placement below vertex. Ventricle size correlated poorly with clinical grade and normal ICP. Only 73% of slit ventricles enlarged by 16.5 months. The need to mimic normal upright ICP by maintaining a normal level of zero upright ICP in shunted patients is supported by these results. PMID- 8456386 TI - Effects of mannitol on cerebral blood flow, blood pressure, blood viscosity, hematocrit, sodium, and potassium. AB - In our miniature swine model of brain retraction ischemia under conditions simulating the neurosurgical operating room, we studied the effects of bolus mannitol (2 g/kg) administration on cerebral blood flow, blood pressure, blood viscosity, hematocrit, sodium, and potassium serially for 4 hours following administration, at which time a second bolus was administered. Both viscosity and hematocrit were significantly decreased transiently following both the first and second boluses. Sodium was decreased for 30 minutes following the first bolus, 15 minutes following the second bolus, and increased at 150 minutes and later following the second bolus. There was a mild decrease in blood pressure and a mild increase in cerebral blood flow following mannitol, but little difference between the first hour following a bolus (when the viscosity and hematocrit were decreased) and hours 2-4 (when they were near baseline). Mannitol's effects on blood pressure and cerebral blood flow probably depend on factors in addition to its effects on blood viscosity and hematocrit. The results are discussed in light of previous findings that bolus mannitol administration may improve cerebral blood flow in ischemia, but does not appear to benefit the preservation of brain electrical activity. PMID- 8456387 TI - A new, rolled-sponge technique for transoral exposure of C1 and C2. AB - Instead of the general use of a catheter attached to the uvula or of catheters passed through the nasal cavity to the mouth for elevation of soft palate, the authors describe a new technique utilizing two rolled sponges producing maximum elevation of soft palate and good perioral cosmetic results for transoral exposure of C1 and C2. PMID- 8456388 TI - Late solitary cerebral metastases from renal cell carcinoma: report of two cases. AB - We report two cases of solitary cerebral metastases from renal cell carcinoma 15 and 18 years after nephrectomy. In a review of the literature, only two cases of solitary brain metastasis from renal cell carcinoma with latency periods greater than 10 years have been documented. Our two cases represent the longest latency periods reported between nephrectomy and detection of a solitary cerebral metastasis. Histologic examination and immunohistochemical profile of the primary renal tumors and metastatic cranial tumors showed identical morphology and immunophenotype. PMID- 8456389 TI - Neural stimulation: clinical and laboratory experiences. AB - This is a report of some of the experiences of the author and his associates with electrical stimulation of the animal and human nervous systems. It was presented as a personal history rather than a review of recent investigations and publications concerned with safe and effective stimulation of neural tissue with the ultimate goals of developing neural prostheses. Much of the information presented herein has been published. PMID- 8456390 TI - Richard A. Lende winter neurosurgery conference. AB - One of the most prestigious and popular winter neurosurgery conferences, the Richard Lende Conference, had its 18th meeting this last winter. It is also the oldest winter neurosurgery conference of this type in this country, and possibly in the world. It is, therefore, of interest to trace its history and to share this information with the neurosurgery community. PMID- 8456391 TI - Newer concepts in the treatment of cancer of the stomach. PMID- 8456393 TI - A gastroplasty that avoids stapling in continuity. AB - BACKGROUND: Staple line perforations have been the principal cause of failure after vertical-banded gastroplasty in patients followed at least 4 years at our institution. In the present study an operation was devised that created a vertical-banded gastroplasty not dependent on staple lines to avoid this complication. METHODS: One hundred two patients with a body mass index (BMI) greater than 35 kg/m2 underwent vertical-banded gastroplasty from Jan. 1 to Dec. 30, 1986, with an orifice size of 45 to 47 mm external circumference and division between the vertical staple lines to prevent gastric pouch to gastric fundus fistula. RESULTS: Ninety-eight of the patients have been followed up for a minimum of 4 years. Sixty-two percent of patients obtained an excellent or good final result after 4.5 +/- 0.1 years. This was a BMI of less than 35 kg/m2 or less than 50% excess weight. This acceptable long-term result was achieved 90% of the time if the patient was obese (BMI, 35 to 40 kg/m2) before surgery and in 75% of patients who were morbidly obese (BMI, 40 to 50 kg/m2) but in only 30% of patients who were superobese (BMI > 50 kg/m2) before surgery. Staple line disruption was markedly reduced; however, stenosis or failure to lose weight or late weight gain required reoperation in 36% of the patients. CONCLUSIONS: Gastric bypass was superior to reversal or revision of the gastroplasty as a remedial operation. This study again questions the value of vertical-banded gastroplasty in the treatment of obesity even when staple line disruption is markedly diminished. PMID- 8456392 TI - Peritoneovenous shunting of intractable ascites in patients with cirrhosis: improving results and predictive factors of failure. AB - BACKGROUND: The clinical results of peritoneovenous shunting have not been entirely satisfactory in spite of dramatic improvement of renal function and decrease of ascites. The purpose of this study is to determine whether certain modifications improved our results. METHODS: A modified LeVeen shunt was electively inserted in 56 patients who had cirrhosis with intractable ascites. In 24 patients (42.9%) the Child-Pugh's score was less than 9, and in 32 patients the score was 9 or above. Fourteen patients (25%) had previous variceal bleeding, and 15 patients (26.8%) had previous spontaneous bacterial peritonitis (SBP). LeVeen shunt was modified by the addition of a titanium venous catheter tip. Prophylactic antibiotic therapy was administered to all patients. RESULTS: No operative deaths occurred, and one patient had severe postshunt coagulopathy. Five patients (8.9%) experienced recurrent ascites resulting from blockage from the shunt. The cumulative rate of shunt blockage was 5.6% at 1 year and 12% at 2 years. Seventeen patients (30.3%) have recently had variceal bleeding. The cumulative risk of variceal bleeding was significantly higher in patients with a previous hemorrhage than in those patients without (p < 0.05). Eight patients (14.3%) had SBP after operation. The cumulative risk of SBP was higher in patients with a history of SBP than in those patients without, although the difference was not significant. Fifty-five percent of late deaths were related to variceal bleeding or to SBP. Overall cumulative 1- and 2-year survival rates were 67.2% and 55.2%, respectively. It was 82% and 71% in patients without previous variceal bleeding or SBP. CONCLUSIONS: These data suggest that peritoneovenous shunting might be beneficial only in selected patients. Previous variceal bleeding and/or SBP indicate liver transplantation in suitable patients. PMID- 8456394 TI - The role of surgery in the treatment of nonregionally recurrent melanoma. AB - BACKGROUND: Between 1971 and 1989, 144 patients underwent 183 surgical procedures for resection of nonregional metastatic melanoma. METHODS: Thirty-six patients with subcutaneous or nodal metastases, 46 patients with pulmonary metastases, 17 patients with brain metastases, 19 with gastrointestinal metastases, and 26 patients with miscellaneous sites of metastatic involvement underwent resection. RESULTS: The overall 5- and 10-year actuarial survival rates were 20% and 14%, respectively. A single postoperative death occurred in a patient operated on for palliative treatment of gastrointestinal metastases. CONCLUSIONS: Cox regression analysis suggests that patients with a solitary metastasis confined to the subcutaneous, nonregional lymph nodes or lung are most likely to benefit from aggressive surgical intervention. Surgical intervention represents a potentially important modality in the management of selected patients with nonregional metastatic melanoma. PMID- 8456395 TI - Donor hepatectomy for living related partial liver transplantation. AB - BACKGROUND: An essential prerequisite for living related partial liver transplantation is to perform donor hepatectomy with minimal risk while preserving graft viability. This article describes a safe method of donor hepatectomy that was used for five patients who underwent living related liver transplantation. METHODS: Liver parenchymal transection was performed by the selective vascular occlusion technique in four patients, and interruption of the blood supply to the left medial segment was carried out along the right side of the umbilical portion before parenchymal division in the other patient. RESULTS: These procedures resulted in insignificant intraoperative blood loss, for which no banked blood or blood derivatives were transfused. The postoperative course for each of the five donors was uneventful, and excellent graft viability was verified by the fact that the five recipients showed a good immediate postoperative course without marked increases in the serum activities of liver enzymes. CONCLUSIONS: We believe that the operative risk of living related donor hepatectomy is minimal if it is performed by experienced liver surgeons with the present procedures. PMID- 8456397 TI - Hormone secretion by normal human parathyroid cells in vitro: characterization by the reverse hemolytic plaque assay. AB - We have recently validated a reverse hemolytic plaque assay (RHPA) for the quantitative measurement of parathyroid hormone release from single isolated parathyroid cells. The information regarding secretory behavior of normal and abnormal parathyroid tissue has been based previously on fluorescent spectroscopy or quantification of immunoreactive parathyroid hormone by radioimmunoassay. Thus, individual differences in secretion and assessment of viability are not clearly measured in these types of experiments. The RHPA has the advantage of allowing measurements of secretory activity in individual viable parathyroid cells. In this report, we have modified the RHPA to measure the release of parathyroid hormone from human cells. This is the first instance of measurement of hormone secretion from human cells, and we present data indicating the specificity of the assay for human parathyroid hormone. The response of normal human parathyroid cells to alterations in extracellular calcium was assessed by two parameters: the ability of an individual cell to secrete parathyroid hormone in response to a stimulus and the recruitment of normal human cells to release parathyroid hormone. This assay will allow elucidation of secretory dynamics in normal and abnormal glands, which may help us to understand the mechanisms involved in parathyroid dysfunction. PMID- 8456396 TI - Changes in energy substrates in relation to arterial ketone body ratio after human orthotopic liver transplantation. AB - BACKGROUND: Changes in energy substrate metabolism, as well as those in arterial ketone body ratio (KBR; acetoacetate/3-hydroxybutyrate), were investigated to follow energy status of hepatic allograft. METHODS: Plasma concentrations of energy substrates were measured immediately after 35 orthotopic liver transplantations in 32 adult patients. RESULTS: Twenty-three patients left the intensive care unit within 1 month (group A), six patients were forced to stay in the intensive care unit longer than 1 month (group B), and the other six grafts failed within 1 month (group C). In group B the KBR was significantly lower than in group A 6 hours after reperfusion of the grafts (0.70 +/- 0.09 vs 1.21 +/- 0.10, mean +/- SEM; p < 0.05). In group C the KBR remained significantly lower than in group A at 6 hours (0.65 +/- 0.04 vs 1.21 +/- 0.10; p < 0.01), on the first postoperative day (0.64 +/- 0.03 vs 1.36 +/- 0.10; p < 0.001), and on the second postoperative day (0.65 +/- 0.02 vs 1.58 +/- 0.11; p < 0.01). Total ketone body concentration (TKB) was significantly higher in group B than in group A at 4 hours (462.9 +/- 105.0 mumol/L vs 201.6 +/- 32.6 mumol/L; p < 0.01), 6 hours (483.4 +/- 102.1 mumol/L vs 125.5 +/- 25.9 mumol/L; p < 0.001), and the first postoperative day (481.1 +/- 196.6 mumol/L vs 123.9 +/- 24.1 mumol/L; p < 0.001). No increase in TKB was observed in group C. CONCLUSIONS: It is suggested that low values in KBR accompanied with low levels of TKB should be regarded as a strong indicator of graft failure and fatty acid oxidation and ketogenic pathways are accelerated to compensate for energy deficits in patients with low values in KBR and high levels of TKB until KBR recovers immediately after orthotopic liver transplantation. PMID- 8456398 TI - Management of arterial injuries produced by percutaneous femoral procedures. AB - BACKGROUND: A significant number of vascular injuries occur with the use of percutaneous diagnostic and therapeutic procedures. This study was done to indicate the types of these injuries and their management. METHODS: Over a 30 month period, 55 patients required operation for vascular complications after percutaneous femoral procedures including infrarenal arteriography (six patients) and angioplasty (22 patients), coronary angiography (16 patients) and angioplasty (five patients), and aortic balloon pump insertion (six patients). RESULTS: The 14 iliac and 41 femoral artery injuries included 29 pseudoaneurysms, six lacerations with persistent bleeding, seven dissections, six occlusions, three ruptures, two arteriovenous fistulas, and two large hematomas. Control for all femoral and distal external iliac artery lesions was obtained solely through a groin incision in 45 (82%) patients. Our technique for exposure of the external iliac artery through the groin is described. A separate retroperitoneal incision was necessary in 10 patients because of proximal injury, massive pseudoaneurysm, morbid obesity, or heavily scarred groins. In this series 34 lateral suture repairs, 11 interposition or bypass grafts, four patch angioplasties, one endarterectomy, three thrombectomies, and two hematoma evacuations were performed. Although no limb loss occurred, we encountered nine wound complications, five myocardial infarctions, and two deaths. CONCLUSIONS: This experience shows the wide variety of vascular complications caused by percutaneous procedures and the different techniques necessary for their management. PMID- 8456399 TI - A new prognostic classification for esophageal atresia. AB - BACKGROUND: Waterston's risk categories have been extensively used in the past for the classification and management of neonates with esophageal atresia. Advances in neonatal care have affected the prognostic usefulness of the Waterston classification. The purpose of this study is to formulate a new classification of risk factors that would more accurately predict outcome. METHODS: We retrospectively reviewed 95 consecutive cases of esophageal atresia and/or tracheoesophageal fistula treated at the Montreal Children's Hospital. Fifteen patients were in the Waterston class A, with a 6.7% mortality; 35 patients, in class B with a 5.7% mortality; and 45 patients, in class C with a 26.7% mortality. Logistic regression analysis of the influence of each risk factor (weight, pulmonary status, and severity of associated anomalies) on mortality was performed. RESULTS: Birth weight was not found to independently influence mortality. Only severe pulmonary dysfunction with preoperative ventilator dependence and severe associated anomalies had a prognostic influence. We therefore revised the classification to include only significant factors. The new high-risk class II consists of patients with either life-threatening anomalies or both major anomalies and ventilator dependence; the low-risk class I includes all other patients. These criteria radically changed the stratification of both the number of cases and the mortality among classes: the 82 patients in class I had a 7.3% mortality; the 13 patients in class II had a 69.2% mortality. Logistic regression analysis confirmed the validity of this new classification by showing displacement of individual variables by the revised classification but not by Waterston's. CONCLUSIONS: This new "Montreal classification" can simplify and improve the stratification of patients with esophageal atresia. It also reflects the more favorable outcome of low birth weight neonates. PMID- 8456400 TI - Effects of lumbar sympathectomy on canine transcutaneous oxygen tension. AB - Augmentation of cutaneous blood flow by postganglionic lumbar sympathectomy may not reflect an increase in nutritive vascular supply to the dermal tissues. Transcutaneous oxygen tension (TcPO2) was compared with radionuclide microsphere determination of dermal microcirculation in a hind limb sympathectomy model in 20 dogs. After 90 minutes the TcPO2 was greater in the sympathectomized limbs than in the contralateral limbs (125 mm Hg versus 114 mm Hg, p < or = 0.05). In contrast, microsphere-determined paw dermal capillary flow declined in sympathectomized limbs (4.9 ml/min/100 gm versus 11.8 ml/min/100 gm, p < or = 0.05). Decreases in the TcPO2/venous PO2 ratio correlated with sympathectomy induced increases in total limb blood flow (r = 0.60; p < or = 0.001), reflecting less efficient oxygen extraction. These observations confirm the lack of enhancement of tissue oxygen delivery by sympathectomy because of the associated dilation of cutaneous arteriovenous shunts. PMID- 8456401 TI - Harvey Cushing: first guest at "The Divine Banquet of the Brayne". AB - Harvey Cushing will remain forever ensconced in surgical memory as the visionary who established contemporary neurosurgery. Raised in Cleveland in a middle-class family with a medical background, he gave little indication early of his later prowess. A college education at Yale University yielded a modest performance, although he showed somewhat better promise as a medical student at Harvard University. During his surgical training at the Johns Hopkins Medical School, he emerged as a bright, industrious young man with a glint of steel to his intellect. From Halsted he learned the academic basis of surgery and the meticulousness necessary for technical success. Osler became his friend and provided him with a foundation in the history of medicine and the recognition of its importance in shaping the future. The decision to spend a year in Europe visiting clinics and renowned surgeons may have laid the foundations for the subsequent configuration of his career. In Britain he saw firsthand the glorious museums and libraries of the Hunters and the legacy that their schools of surgery had endowed to the nation. In Paris and London he mixed with the surgical aristocracy of the times and learned the power of societies and the traditions of their patrons. In Berne he was exposed to the surgical purity and physiologic expertise of Kocher, supported by the estimable scientific practice of Kroneker. As an "arbeid," Kocher posed him the problem of establishing the mechanism of the regulation of cerebral perfusion. This question, which he so rapidly and successfully unraveled, probably played a large part in igniting his enthusiasm toward the study of the brain as a future career. In his travels he encountered diverse intellects and experienced a wide panoply of European medical thought. He conversed widely at both a social and professional level and integrated all information into meticulously kept diaries that served as not only a record but also a template from which later plans were derived. A final 6-week sojourn in Liverpool working on the primate cortex with Sherrington, the greatest neurophysiologist of that time, may have sealed his decision to turn his initial project with Kocher into the opus of a lifetime. The 14-month tour of Europe transformed Cushing from a relative unsophisticate into a figure of giant proportions. All that he experienced became part of his life and was integrated into his subsequent career.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8456402 TI - Recurrent hyperparathyroidism from benign neoplastic seeding: a review with recommendations for management. AB - Benign neoplastic seeding represents a rare cause of hyperparathyroidism found at parathyroid reoperations. It consists of pathologically benign neoplastic parathyroid tissue scattered throughout a previous parathyroid surgical site. We describe a case of recurrent and then persistent hyperparathyroidism occurring in a patient during an 18-year period. The patient's third operation showed nonmalignant parathyroid tissue throughout the right neck bed, which necessitated extensive parathyroid and fibrofatty tissue dissection and a thyroidectomy. This unexpected finding of extensive parathyroid seeding has only been described in detail in ten other patients in the past. A review of these 11 patients shows several features: initial operations were for large parathyroid tumors or cysts in six patients; rupture and spillage of contents occurred in six; and initial hypercalcemia was severe in several patients, perhaps indicating inherently more aggressive tumors. The appearance of benign neoplastic seeding resembled parathyroid carcinoma in its local invasiveness. Therefore the presence of anaplasia, mitoses, capsular invasion, and cellular spindling must be relied on as distinguishing factors. When confronted with this presentation, we recommend removal of all nodal bearing, thyroid, and fibrofatty tissue from the level of the thyroid cartilage to the superior mediastinum and a thyroidectomy if necessary. PMID- 8456403 TI - Fivefold enlargement of implants in a splenic autotransplant recipient. AB - A 30-year-old patient underwent splenectomy for trauma with splenic autotransplantation. Four years later he survived a bout of pneumococcal sepsis with only oral penicillin therapy. Seven years after splenectomy, he underwent another laparotomy with the finding of fivefold enlargement of the splenic implants. Splenic autotransplants enlarge and probably function in human beings. PMID- 8456404 TI - High-output cardiac failure: an unusual manifestation of intravenous leiomyomatosis. AB - Intravenous leiomyomatosis is a rare uterine neoplasm characterized by nodular or wormlike masses of histologically benign smooth muscle growing within myometrial veins and extending variable distances into the veins of contiguous organs and major pelvic veins. In some cases, there has been extension into the gonadal or iliac veins to the vena cava and right atrium, causing symptoms of congestive heart failure and an eventual fatal outcome. We present a report of the first case in which high-output cardiac failure was caused by the development of arteriovenous shunting within the intravenous component of the tumor that involved the pelvic organs and retroperitoneal and gonadal veins but not the vena cava. Treatment by total abdominal hysterectomy, bilateral oopherectomy, and tumor mass excision from the retroperitoneum was successful. PMID- 8456405 TI - Dextrocholedocholithiasis: calculous obstruction complicating double ductus choledochus in an adult. AB - Double ductus choledochus is a rare anomaly of the extrahepatic biliary tree in which the common bile duct is represented by two independent hepatic ducts. Patients with this abnormality may have unimpeded biliary drainage and remain symptom free, yet various forms of double ductus choledochus are occasionally encountered in patients undergoing operation for symptomatic cholelithiasis. We describe a patient in whom doubled biliary ducts were identified on exploration for cholecystectomy along with calculous obstruction of the right-sided duct (ductus choledochus dextri). This case illustrates the potential for significant injury to the biliary tree when double ductus choledochus is present. In addition to a means by which to manage this problem at the time of operation, a review of the literature, as well as a description of this rare embryologic abnormality, is presented. PMID- 8456406 TI - The importance of arterial reconstruction in liver transplantation in rats. PMID- 8456407 TI - Role of super-specialty fellowships. PMID- 8456408 TI - Usefulness of endoscopic ultrasonography for the localization of insulinomas. PMID- 8456409 TI - Putting people first in Texas' budgetary priorities. PMID- 8456410 TI - AIDS Q&A. PMID- 8456411 TI - Put the needs of people first! PMID- 8456412 TI - Legal issues for nurses. Informed consent: whose responsibility? PMID- 8456413 TI - [Autoimmune chronic active hepatitis]. AB - Autoimmune chronic active hepatitis is a rare type of chronic active hepatitis which occurs with a bimodal age distribution (10 to 30 or > or = 50 years) most frequently in women. It is characterized by negative markers for other possible (e.g. viral) etiologies, hypergammaglobulinemia and a number of circulating autoantibodies. According to the latter, several subgroups can be discriminated today. Histology shows chronic active hepatitis with chronic, sometimes plasma cell-rich infiltration of portal tracts and piece-meal necroses. Symptoms and signs are classically non-specific and include general malaise, lethargy and fatigue. Accompanying autoimmune diseases may be present. The disease is today, however, also frequently diagnosed in an early, asymptomatic stage. Cause(s) and pathogenetic mechanism(s) of the increasingly heterogeneous appearing disease remain unknown. Recent observations seem to indicate that as yet undetermined (exogenous) substance(s) and the hepatitis C virus may, at least in certain subgroups, trigger autoimmune reactions, which may then perpetuate on the basis of a permissive (immuno)genetic background. Untreated, the disease is, in general, progressive, leads to cirrhosis and shows a mortality of up to > or = 50% in 2 to 4 years. Signs potentially indicating a nonfavorable prognosis include high inflammatory activity and the presence of cirrhosis at diagnosis. Typically, immunosuppressive therapy with corticosteroids (with or without azathioprine) results in remission of inflammatory, but usually not fibro-genetic activity with its potential for cirrhosis. Exacerbations after cessation of treatment are not infrequent (> or = 50%), and indefinite therapy is required in a number of patients, despite its potential for unwanted effects (e.g. osteopenia). Such therapy may increase the 5-year survival rate to > 80%. Liver transplantation remains the sole therapeutic option in end stage disease. PMID- 8456414 TI - [Psoriasis, an autoimmune disease?]. AB - Whereas psoriasis is well defined as a clinical entity for more than a century, the pathogenesis of psoriasis is still open to debate, despite demonstration of multiple abnormalities in cell-kinetics, histomorphology and biochemistry. Recent research indicates altered immune function in psoriatic skin, which may explain some of the phenomena typical for this disease. The role of immunological pathomechanisms in psoriasis is further substantiated by the well-known success of immunosuppressive treatments. However, as long as putative auto-antigens, which are presumed to perpetuate the pathological immune reactions, are not identified, psoriasis cannot be classified as an autoimmune disease. PMID- 8456415 TI - [Will type I diabetes mellitus be treated with immunosuppressive drugs in the future?]. AB - Even if the pathogenesis of type-I (insulin-dependent) diabetes mellitus is still not clarified in every detail, there is general agreement that this form of diabetes is induced by autoimmune mechanisms leading to beta-cell destruction. Therefore, it should theoretically be feasible to suppress the mechanism leading to type-I diabetes with appropriate and early immunotherapy. The current clinical data clearly document that the rate and duration of remissions in patients with newly diagnosed type-I diabetes can be increased significantly using appropriate immunosuppressive regimens. However, before these therapies can become standard therapy of type-I diabetes, the following important clinical requirements have to be fulfilled: the toxicity (especially to kidneys and beta-cells) has to be reduced, the patients should be diagnosed and treated in 'pre-diabetic' states, more selective immunosuppressive regimens have to be available in order to reduce the occurrence of treatment-associated lymphomas and neoplasias. Since accurate detection of 'pre-diabetic' patients is difficult and presents an immense logistic problem, it may take a long time before large-scale immunosuppressive therapies of type-I diabetes are feasible. PMID- 8456416 TI - [Immunosuppressive therapy of glomerulonephritis--controlled studies]. AB - Glucocorticoids, cytostatic agents and cyclosporin are frequently employed in the treatment of glomerular diseases of immunologic origin. In order to assess the efficacy of these drugs, we retrieved--with the help of a Medline-based search- and analysed all controlled studies published since 1966 dealing with immunosuppressive therapy of glomerulonephritis. Of the 34 identified controlled studies, only 27 had a prospective and randomized design. In patients with minimal-change glomerulonephritis, proteinuria decreases and disappears during therapy with prednisone. A comparable effect can be obtained with cyclosporin. Occasionally, there is a relapse of proteinuria after cessation of the immunosuppressive therapy in some patients. These relapses can be controlled with a chlorambucil-based regimen. Chlorambucil may be successfully utilized in the treatment of focal-segmental glomerulosclerosis, a form of glomerulonephritis which is more refractory to glucocorticoid therapy and is probably pathogenetically related to minimal-change glomerulonephritis. Patients with membranous glomerulonephritis and a nephrotic syndrome seem to benefit from an alternate month prednisone and chlorambucil regimen. However, an indiscriminate treatment of all patients with this regimen is not legitimate, because some patients would be overtreated as the disease may undergo spontaneous remission. There are no well-documented valuable therapies for the IgA-associated glomerulonephritis and the membranoproliferative glomerulonephritis. The combination of prednisone with cytotoxic substances, particularly cyclophosphamide and azathioprine, seem to remarkably improve the renal prognosis of the diffuse proliferative lupus glomerulonephritis. The efficacy of cyclophosphamide and prednisone with or without plasma exchange in the treatment of the rapidly progressive glomerulonephritis due to other systemic diseases (M. Wegener, panarteritis nodosa, Goodpasture syndrome) is a widely accepted therapeutic modality, although controlled studies are lacking. Immunosuppressive therapy of glomerulonephritis bears notable risks and sometimes questionable efficacy. Thus, before prescribing any immunosuppressive therapy, it is mandatory to evaluate in every single patient the prognostic factors of the underlying disease, the probability of the onset of severe side effects and the possible acceptance of a renal replacement therapy, including renal transplantation. PMID- 8456417 TI - [Model concepts on the development of so-called autoimmune diseases]. AB - The etiology and pathogeneses of autoimmune diseases are only known in a few examples such as myasthenia gravis, some thyroid affections or some forms of pemphigus. This review uses a few experimental models to argue that many autoimmune diseases, particularly those mediated by or dependent upon T cells, may represent immunopathologies triggered by either trivial or unrecognized special infectious agents. In those instances where we know the etiologic agent we call the ensuing disease immunopathological, and in those where we do not know the agent we call it autoimmune. PMID- 8456418 TI - [Mechanism of action of immunosuppressive agents]. AB - In addition to T and B cells, accessory cells such as macrophages are necessary for an immune response to occur. At present it is probably reasonable to regard collaborative immune response as a series of interrelated processes in which antigen-specific recognition is performed and in which various nonspecific mediators function as modifiers to regulate the intensity and quality of the response. According to this model, immunosuppressive drugs interfere at different stages and levels of the immune response. Glucocorticoids inhibit preferentially the activities of monocytes and T-helper cells as well as lymphokine production. Cyclosporin effectively inhibits the production of interleukin-2 and influences selectively the action of the T lymphocytes. Azathioprine, cyclophosphamide and methotrexate decrease the proliferative response of all the cells involved in the immune response. The immunosuppressive activity of chloroquine is still not well established, but the drug seems to have inhibitory effect on thromboxane and interleukin-2 production. Whole populations of lymphoid elements are destroyed by administering antibodies against surface determinants of these lymphoid elements. Antiidiotypic antibodies, present in intravenous immunoglobulin preparations from pools of donors, are capable of eliminating circulating (auto-)antibodies by binding to the idiotypic region of a specific disease-associated antibody. PMID- 8456419 TI - [Cost-benefit relationship of serologic studies in autoimmune diseases]. AB - Autoimmune disorders are mainly clinically defined disease entities. The diagnosis of many of the systemic autoimmunopathies is based on characteristic combinations of symptoms, some of them overlapping various kinds and being of unspecific nature. Therefore, laboratory parameters such as autoantibodies, components of the complement system, some cytokines and their receptors, etc., are used for the diagnosis, although many of them are of limited specificity and sensitivity. The most important immunoparameters being of value for diagnosis and disease monitoring are discussed, and a stepwise procedure is proposed in order to reduce the costs. Basis are the screening tests for antinuclear antibodies (ANA) and for antibodies against cytoplasmatic components of granulocytes (ANCA). Depending on more specific questions, other tests and test combinations are then applied in second and third priorities. PMID- 8456420 TI - [Cost-conscious procedure in treatment of autoimmune thrombocytopenic purpura]. AB - Autoimmune thrombocytopenic purpura is a common hematologic autoimmune disease. Approximately three fourth of the patients respond to corticosteroids or splenectomy and need no further treatment. Patients refractory to these two therapeutic approaches are relatively resistant to other forms of treatment and are at much greater risk for morbidity and mortality. The therapeutic choice for the refractory patient depends on the age of the patient, the degree of thrombocytopenia, on compliance, toxicity, costs of the treatment and expected duration of the response. Since there is no universal option for all patients, physicians and patients must be prepared to try several approaches over a long period of time. PMID- 8456421 TI - A study of the use of the thromboxane A2 antagonist, sulotroban, in combination with streptokinase for local thrombolysis in patients with recent peripheral arterial occlusions: clinical effects, platelet function and fibrinolytic parameters. AB - In peripheral thrombolysis adjuvant anti-platelet therapy may help to lyse otherwise resistant thrombus, thereby increasing the number of patients successfully treated and reducing the "time to lysis". If continued after lysis it may help to prevent early rethrombosis. In this pilot study 21 patients undergoing peripheral thrombolysis with streptokinase were randomised to receive the thromboxane receptor antagonist sulotroban or placebo. The dose of sulotroban given was 2 mg/min (four patients), 4 mg/min (five patients) or 8 mg/min (four patients), eight patients received placebo. The clinical and laboratory effects of the treatment were monitored. Thrombolysis was achieved more quickly in patients receiving sulotroban, however, there was no difference between groups in the number of patients in whom recanalisation was achieved (six of eight receiving placebo and eight of 13 receiving sulotroban) or in the number of cases of early rethrombosis. During lysis there was an increase in plasma beta thromboglobulin with similar levels being found in patients receiving sulotroban and streptokinase and those receiving streptokinase alone. No other major changes in platelet function during lysis were seen in patients receiving streptokinase alone. Sulotroban significantly reduced platelet aggregation and 14C-5HT release in response to several platelet agonists. With the thromboxane mimetic U46619 the degree of inhibition of aggregation and 14C-5HT release depended on the dose of sulotroban used. High levels of inhibition were associated with an excess of haemorrhagic complications especially in combination with a low plasma fibrinogen level. We conclude that the use of low dose sulotroban in combination with streptokinase merits further study and may hve a role in accelerating lysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8456422 TI - A higher than expected incidence of factor VIII inhibitors in multitransfused haemophilia A patients treated with an intermediate purity pasteurized factor VIII concentrate. AB - In May 1990, 218 patients with haemophilia A regularly attending the Leuven Haemophilia Center were randomly assigned to a group receiving either of two newly introduced factor VIII concentrates: factor VIII-P, an intermediate purity pasteurized concentrate, or factor VIII-SD, a high purity concentrate treated with solvent-detergent for viral inactivation. Patients were followed from May 1990 until October 1991. Between August 1991 and October 1991 a clinically important factor VIII inhibitor was detected in five out of the 109 patients receiving factor VIII-P while none of the 109 patients receiving factor VIII-SD developed such antibodies. All patients acquiring an inhibitor had previously been clinically tolerant to transfused factor VIII with 200 to more than 1,000 days of exposure to factor VIII prior to May 1990. Patients with inhibitors were transfused daily with 30 U factor VIII-SD per kg body weight, which was associated with a gradual decline of the inhibitor level. In all patients the antibodies were relatively slow-acting and predominantly directed towards the light chain of factor VIII. This study demonstrates a higher than expected incidence of factor VIII inhibitors associated with the use of a specific factor VIII concentrate in multitransfused haemophilia A patients. It indicates the usefulness of evaluating newly introduced concentrates in prospective, randomized trials. PMID- 8456423 TI - Protease nexin 1 is expressed in the human placenta. AB - Protease nexin 1 (PN1), a serine protease inhibitor that inactivates thrombin, urokinase, and plasmin, is produced abundantly in cultures of human fibroblasts and rat and human glioma cells. The major sites of PN1 synthesis in vivo and the specific physiological function(s) of this serpin are unknown. Using Northern blot analysis and a full-length PN1 cDNA probe we demonstrated the presence of PN1 mRNA in human term placentas. In situ hybridization of placental tissue with a PN1 riboprobe showed that PN1 mRNA is present throughout the placenta and is also abundant in the placental membranes. Immunohistochemical analysis with an anti-PN1 antibody showed co-localization of PN1 and its mRNA within the placenta. PMID- 8456424 TI - Plasma factor V activation is prevented by activated protein C in the presence of phospholipid vesicles, not platelets. AB - Activated protein C (APC) is a vitamin K dependent anticoagulant which catalyzes the inactivation of factor V a and VIII a, in a reaction modulated by phospholipid membrane surface, or blood platelets. APC prevents thrombin generation at a much lower concentration when added to recalcified plasma and phospholipid vesicles, than recalcified plasma and platelets. This observation was attributed to a platelet associated APC inhibitor. We have performed serial thrombin, factor V one stage and two stage assays and Western blotting of dilute recalcified plasma containing either phospholipid vesicles or platelets and APC. More thrombin was formed at a given APC concentration with platelets than phospholipid. One stage factor V values increased to higher levels with platelets and APC than phospholipid and APC. Two stage factor V values decreased substantially with platelets and 5 nM APC but remained unchanged with phospholipid and 5 nM APC. Western blotting of plasma factor V confirmed factor V activation in the presence of platelets and APC, but lack of factor V activation with phospholipid and APC. Inclusion of platelets or platelet membrane with phospholipid enhanced rather than inhibited APC catalyzed plasma factor V inactivation. Platelet activation further enhanced factor V activation and inactivation at any given APC concentration. Plasma thrombin generation in the presence of platelets and APC is related to ongoing factor V activation. No inhibition of APC inactivation of FVa occurs in the presence of platelets. PMID- 8456426 TI - Cytokine regulation of the synthesis of plasminogen activator inhibitor-2 by human vascular endothelial cells. Comparison with plasminogen activator inhibitor 1 synthesis. AB - Plasminogen activators are inhibited by plasminogen activator inhibitors-1 (PAI 1) and -2 (PAI-2). We describe the synthesis of PAI-2 by human vascular endothelial cells (EC) cultured from umbilical vein, saphenous vein and foreskin microvasculature in response to interleukin-1 alpha (IL-1 alpha) and tumour necrosis factor alpha (TNF alpha) and compare it with that of PAI-1. Both PAI-2 and PAI-1 were quantitated by ELISAs. PAI-2 was cell-associated while PAI-1 was secreted by EC. IL-1 alpha and TNF alpha increased the synthesis of PAI-2 and PAI 1 by EC in a dose-dependent manner. IL-1 alpha was a stronger stimulus for PAI-2 synthesis than TNF alpha, while both cytokines were equally effective for PAI-1. Northern blot analysis revealed similar changes in mRNA levels to those in antigen levels. PAI-2 synthesis by cytokine-stimulated EC may be important in thrombus formation and inflammation. PMID- 8456425 TI - The effect of antithrombin III-independent thrombin inhibitors and heparin on fibrin accretion onto fibrin-coated polyethylene. AB - Prosthetic vascular grafts become coated with a layer of fibrin that contributes to graft thrombosis and occlusion. We compared the effect of antithrombin III independent inhibitors of thrombin with heparin for their ability to prevent fibrin accretion onto a model of a vascular graft formed in vitro by coating polyethylene tubing with thrombin bound to a layer of polymerized fibrin. Equivalent antithrombin concentrations of heparin, D-Phe-Pro-Arg CH2Cl (PPACK), recombinant hirudin (r-hirudin), and Hirulog-1 were added to barium chloride absorbed plasma containing radiolabelled fibrinogen. Whereas, PPACK and r-hirudin persistently inhibited fibrin accretion, the inhibition by heparin was transient. Hirulog-1 had no effect on early fibrin accretion and was actually associated with enhanced accretion at 30 min (control 11.7 +/- 2.0 micrograms fibrin/cm2; Hirulog-1, 18.4 +/- 3.5 micrograms fibrin/cm2, p < 0.001). Both Hirulog-1 and r hirudin displaced radiolabelled thrombin from the fibrin surface. Whereas hirudin thrombin complexes are stable, Hirulog-1 produces only transient inhibition of the displaced thrombin thereby accounting for the enhanced fibrin accretion with this anticoagulant. These studies show that the antithrombin III-independent inhibitors, r-hirudin and PPACK, are more effective inhibitors of fibrin accretion onto fibrin-coated polyethylene than heparin or Hirulog-1. In addition, they emphasize the importance of determining the ability of anticoagulants to displace thrombin from fibrin and to form stable thrombin-inhibitor complexes; lack of stability of thrombin-inhibitor complexes must be countered by levels of anticoagulant that are adequate to maintain its effectiveness. PMID- 8456427 TI - Therapeutic effect of a low molecular weight dermatan sulphate (Desmin 370) in rat venous thrombosis--evidence for an anticoagulant-independent mechanism. AB - We evaluated the capacity of a low molecular weight dermatan sulphate (D370) to prevent thrombus formation and to induce a reduction of a stabilized thrombus in a rat venous thrombosis model. Injection of D370, 10 min before induction of venous stasis (prevention model), prevented thrombus formation in a dose dependent way (ED50: 2.3 mg/kg). When given to rats 6 h after induction of venous stasis (therapeutic model), D370 caused a time- and dose-dependent reduction in thrombus size (60% to 70% reduction 2 h after injection of 10 mg/kg). At comparable antithrombotic dosages (i.e. minimum dose giving complete inhibition of thrombus formation), heparin (0.5 mg/kg) only caused 40% reduction of a preformed thrombus while hirudin (1 mg/kg) was virtually ineffective (less than 10% reduction in weight). All three compounds inhibited 125I-fibrin(ogen) deposition on 6-h aged thrombi by more than 85%, suggesting that D370 and, to a lesser extent, heparin reduce thrombus size via mechanisms other than inhibition of thrombus accretion. The involvement of a fibrinolysis-mediated mechanism in the D370-induced effect is suggested by the following. EACA (1 g/kg), when given to thrombus-bearing control animals, did not influence thrombus weight. However, when administered before D370 treatment, it prevented the expected reduction in thrombus weight by more than 80%, without influencing the effect of D370 on 125I fibrin(ogen) accumulation onto preexisting thrombi. D370 injection caused neither an enhancement of fibrinolytic activity nor a reduction of PAI in plasma. In vitro, D370 (200 microns/ml) was unable to potentiate the spontaneous or PA induced lysis of 125I-fibrinogen labelled blood, plasma, or purified fibrin clots.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8456428 TI - Anticoagulant activity of Hirulog, a direct thrombin inhibitor, in humans. AB - Hirulog (BG8967) is a direct thrombin inhibitor built by rational design using the protein hirudin as a model (Maraganore et al. [1990]; Biochemistry 29: 7095 101). In order to evaluate the therapeutic potential for hirulog in the management of thrombotic disease, the tolerability and anticoagulant activity of the agent were examined in a study of human volunteers. In a randomized, placebo controlled study (n = .54), the intravenous infusion of hirulog over 15 min showed a rapid, dose-dependent prolongation of activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). There was a corresponding dose-dependent increase in plasma hirulog levels. The peptide was rapidly cleared with a half-life of 36 min and a total body clearance rate for the peptide of 0.43 l kg-1 h-1. Similar activity was observed following subcutaneous injection but with sustained pharmacodynamic and pharmacokinetic behavior. There was a significant correlation between pharmacokinetic and pharmacodynamic variables for both intravenous (r = 0.8, p < 0.001) and subcutaneous administration (r = 0.7, p = 0.002). To evaluate the possible interactions of aspirin on the tolerability and anticoagulant activity of intravenous hirulog, a cross-over design was employed in eight subjects. Aspirin administration did not modify the peptide's activity. At the administered dose of 0.6 mg kg-1 h-1 for 2 h, hirulog infusion prolonged APTT from 230 to 260% baseline. The infusion of hirulog in subjects who had received aspirin was not associated with any significant changes in the template bleeding time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8456429 TI - Inflammatory and procoagulant mediator interactions in an experimental baboon model of venous thrombosis. AB - Theoretic and in vitro evidence suggests that thrombosis and inflammation are interrelated. The purpose of the present study was to define the relationship between inflammation and deep venous thrombosis (DVT) in an in vivo model. Initiation of DVT was accomplished by administration of antibody to protein C (HPC4, 2 mg/kg) and tumor necrosis factor (TNF, 150 micrograms/kg); stasis; and subtle venous catheter injury. Thrombosis was assessed by thrombin-antithrombin assay (TAT), 125I-fibrinogen scanning (scan) over both the proximal and distal iliac veins, and ascending venography. Cytokines TNF, interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and interleukin-8 (IL-8) were measured along with differential white blood cell counts, platelet counts, fibrinogen (FIB), and erythrocyte sedimentation rates (ESR). Baboon pairs were sacrificed on day 3 (T + 3d), T + 6d, and T + 9d and veins removed. All animals developed inferior vena cava and left iliofemoral DVT by venography; no right DVT was found. TAT was elevated by T + 1hr and peaked at T + 3hrs. Left iliofemoral DVT was found at T + 1hr by scan and reached a 20% uptake difference between the affected left and nonaffected right side at T + 3hrs. TNF peaked at T + 1hr; MCP 1 peaked at T + 6hrs; IL-8 and IL-6 peaked on T + 2d; all cytokines declined to baseline. TNF and TAT elevations were found to correlate with all cytokines; elevations in IL-8 were correlated with elevations in MCP-1 and IL-6 (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8456431 TI - von Willebrand disease: a database of point mutations, insertions, and deletions. For the Consortium on von Willebrand Factor Mutations and Polymorphisms, and the Subcommittee on von Willebrand Factor of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. AB - The current system for the diagnosis and classification of von Willebrand disease (vWD) is quite complex, with more than 20 distinct variants described. Over the past few years considerable progress has been made toward an understanding of vWD at the molecular level. A small cluster of mutations within the vWF A1 homologous repeat appears responsible for over 90% of type IIB vWD. A similar cluster of mutations in the vWF A2 homologous repeat accounts for the majority of type IIA vWD. By RFLP analysis, several type II vWD mutations have been shown to be recurrent on distinct haplotype backgrounds, suggesting independent genetic origins (see accompanying manuscript for a complete list of known polymorphisms). Several mutations at the N-terminus of the mature vWF subunit have been identified in association with abnormal factor VIII binding. Homozygotes for this abnormal vWF present with a hemophilia-like phenotype that is autosomal recessive in inheritance. In a small subset of patients with type III vWD large gene deletions have been identified on one or both vWF alleles. Carriers heterozygous for a deleted locus and one normal vWF gene are generally asymptomatic. Nonsense mutations and other defects resulting in loss of vWF mRNA expression from one allele have also been associated with a recessive type III vWD phenotype. No distinct molecular defect responsible for classic type I vWD has yet been defined. PMID- 8456430 TI - The genetic defect of type I von Willebrand disease "Vicenza" is linked to the von Willebrand factor gene. AB - Type I von Willebrand disease (vWD) Vicenza is a rare variant with autosomal dominant transmission, characterized by the presence of supranormal von Willebrand factor (vWF) multimers in plasma, similar to those normally found in endothelial cells and megakaryocytes. The patients have very low levels of plasma vWF contrasting with a mild bleeding tendency. The pathophysiology of this subtype is still unknown. The presence of supranormal multimers in the patients' plasma could be due to a mutation in the vWF molecule which affects post translational processing, or to a defect in the cells' processing machinery, independent of the vWF molecule. In order to determine if type I vWD Vicenza is linked to the vWF gene, we studied six polymorphic systems identified within the vWF gene in two apparently unrelated families with type I vWD Vicenza. The results of this study indicate a linkage between vWF gene and the type I vWD Vicenza trait. This strongly suggests that type I vWD Vicenza is due to a mutation in one of the vWF alleles, which results in an abnormal vWF molecule that is processed to a lesser extent than normal vWF. PMID- 8456432 TI - A database of polymorphisms in the von Willebrand factor gene and pseudogene. For the Consortium on von Willebrand Factor Mutations and Polymorphisms and the Subcommittee on von Willebrand Factor of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. AB - Nucleotide sequence polymorphisms in the von Willebrand factor (vWF) gene are useful for genetic studies in von Willebrand disease (vWD). This database describes 33 known vWF polymorphisms distributed throughout the vWF gene. DNA sequence information is available for 21 of these sites. The most informative system is a tetranucleotide repeat polymorphism in vWF intron 40. Sixteen of these polymorphisms are within vWF exons, and approximately half of them also alter the encoded amino acid sequence. Many occur close to mutations that cause vWD. The high prevalence of vWF polymorphisms must be considered in the analysis of candidate vWD mutations. In addition to the vWF gene on chromosome 12, there is a partial unprocessed vWF pseudogene on chromosome 22 that corresponds to vWF exons 23 to 34. Three polymorphisms have been assigned to the vWF pseudogene. Because the vWF gene and pseudogene have diverged only approximately 3.1% in DNA sequence, correct assignment of polymorphisms to either locus can be difficult in the region of homology. This problem has been solved in some cases by comparison of the published sequences and predicted restriction maps for the gene and pseudogene. PMID- 8456433 TI - A role for von Willebrand factor proline residues 702-704 in ristocetin-mediated binding to platelet glycoprotein Ib. AB - Mutant domains of von Willebrand factor (vWF) were constructed to determine the effects of altering net charge, and presumably conformation, within a peptide sequence (residues 694-708) previously shown to be involved in the platelet receptor glycoprotein (GP) Ib binding function of vWF. Non-conservative substitutions replaced a triplet of proline residues (proline702-704) with either a triplet of arginine (positively-charged) or aspartic acid (negatively-charged) residues. After establishing stable CHO cell transformants, we observed the secretion of covalently-linked dimeric molecules analogous to a domain with native sequence. Functional assays using immunopurified molecules revealed that the ristocetin-dependent binding to GP Ib was abolished with both charge mutants. However, in the absence of disulfide-bond dependent conformation both mutant molecules and the molecule with native sequence interacted with GP Ib. The results demonstrate that vWF proline702-704 are important for the ristocetin mediated interaction between vWF and GP Ib, but are not essential residues of the GP Ib binding site within vWF. PMID- 8456434 TI - Two independent binding sites on monolayers of human endothelial cells are responsible for interaction with coagulation factor VII and factor VIIa. AB - The interaction of radiolabeled factor VII (FVII) and factor VIIa (FVIIa) with endotoxin-stimulated endothelial cells (EC), known to express tissue factor (TF), and unstimulated EC was studied. FVII/FVIIa binding to EC-monolayers was saturable within 4.5-6 h, reversible, temperature and calcium dependent on both, endotoxin-stimulated and on unstimulated EC. Upon 2 h of incubation on EC, FVII was partially converted to FVIIa in the absence of protease inhibitors. The affinity of this binding was Kd = 45.4 +/- 18.7 nM with a calculated number of binding sites Bmax = 3.75 +/- 0.31 x 10(6) molecules/cell. In addition to unlabeled FVII and FVIIa, other vitamin K-dependent proteins reduced binding of [125I]-FVII/FVIIa to about 60-70%, and this type of common binding site for vitamin K-dependent proteins revealed a Kd = 32.2 +/- 5.6 nM and a Bmax = 3.03 +/ 0.14 x 10(6) molecules/cell. Moreover, in the presence of 1 microM prothrombin to suppress common binding sites, only on endotoxin-stimulated EC additional inhibition of FVII/FVIIa binding was achieved by anti-TF antibodies. The characteristics of the FVII/FVIIa-TF interaction with a Kd = 17.2 +/- 5.2 nM and a Bmax = 342,000 +/- 1,100 binding sites/cell revealed a similar saturation kinetics in radioligand binding and in functional factor X activation within 90 120 min. These data indicate the presence of at least two independent binding sites for FVII/FVIIa on stimulated EC of which about 10% are TF specific.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8456435 TI - Human tumor procoagulants: registry of the Subcommittee on Haemostasis and Malignancy of the Scientific and Standardization Committee, International Society on Thrombosis and Haemostasis. PMID- 8456436 TI - Cimetidine and platelet function in peptic ulcer patients. PMID- 8456437 TI - Reduction of mortality with antithrombin III in septicemic rats: a study of Klebsiella pneumoniae induced sepsis. AB - Experimental gram-negative sepsis was induced in the rat by Klebsiella pneumoniae. Although bacteria are susceptible to the treatment with the antibiotic Tobramycin, DIC could not be prevented. DIC was manifested by a leuko- and thrombocytopenia, decreases in fibrinogen and AT III and an increase of the aPTT. In this model the therapeutic treatment with human AT III was evaluated. To determine the optimal concentration of AT III a prestudy in a LPS induced DIC in the rat was performed. It was shown that a bolus i.v. injection of 500 U/kg improved survival and DIC, and was thus chosen for the Klebsiella sepsis model. The infectious load was adjusted to yield a mortality rate of 90-100% in the untreated Klebsiella group and a reduction to about 40-50% of the mortality rate by Tobramycin. It was found that AT III reduced mortality in the Klebsiella induced sepsis not only when given prophylactically but was effective even when administrated in a late stage of the DIC, i.e. 3 or 5 h post infection. PMID- 8456438 TI - Rapid DNA typing of class II HLA antigens using the polymerase chain reaction and reverse dot blot hybridization. AB - A nonisotopic oligotyping method using reverse dot blot hybridization was developed for HLA class II DQA1, DQB1, DPB1, DRB1, DRB3, DRB4, DRB5 alleles. The polymorphic second exon of the different genes was amplified by the polymerase chain reaction (PCR). For each gene the amplified DNA was hybridized at stringent conditions to membrane-bound sequence-specific oligonucleotides (SSOs) and visualization of positive signals was done by chemiluminescence. A combination of 11, 18, 23 and 31 SSOs was designed to identify 9/13 DQA1, 16/17 DQB1, 23/24 DPB1 and 50/55 DRB1, 4 DRB3, 1 DRB4, 3/4 DRB5 alleles respectively. For the DRB1 locus, an additional DRB1*04 group-specific PCR was developed to make discrimination between the DR4 alleles possible in different heterozygous combinations. The procedure described here provides rapid and nonisotopic genotyping of heterozygous samples from a variety of sources and can be applied for tissue typing, disease susceptibility studies and forensic medicine. PMID- 8456439 TI - Difference in HLA-linked genetic background between mixed connective tissue disease and systemic lupus erythematosus. AB - We have typed 64 Japanese patients with mixed connective tissue disease (MCTD) and 53 Japanese patients with systemic lupus erythematosus (SLE) for HLA-DRB1, DRB3, DRB4, DRB5, DQA1, DQB1, and DPB1 genes by the HLA-DNA typing method using the PCR-SSOP technique. Frequencies of HLA-DRB1*0401, DRB1*0901, DRB4*0101, and DQA1*03 were increased and those of HLA-DRB1*0405 and DQB1*0401 were decreased in the patients with MCTD, while the frequencies of HLA-DRB1*1501, DRB5*0101, and DQB1*0602 were increased in the patients with SLE. The typing results suggest that susceptibility to MCTD is strongly associated with the HLA-DRB1*0401 DRB4*0101-DQA1*03-DQB1*0301 haplotype, and that to SLE is associated with the HLA DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602 haplotype. The observation that the MCTD associated HLA alleles are distinct from the SLE-associated ones may support the clinical entity of MCTD different from SLE. PMID- 8456440 TI - HLA-DR1 and rheumatoid arthritis in Israeli Jews: sequencing reveals that DRB1*0102 is the predominant HLA-DR1 subtype. AB - Rheumatoid arthritis (RA) is associated with the HLA-DR4 cellular subtypes Dw4 and Dw14 in Caucasians, with Dw15 in Japanese, and possibly with HLA-DR1 in Israeli Jews. Sequencing studies in Caucasians have shown that these molecules share a common amino acid sequence in the third hypervariable region of the DR molecule (AA 67-74: LLEQRRAA or LLEQKRAA), suggesting that this sequence is primarily associated with RA. An important argument in favor of this shared epitope hypothesis has been the reported association between DR1 and RA in Israeli Jews. However, a later report did not confirm this association, and cellular typing showed that Israeli DR1 consists of three or more subtypes, suggesting that new subtypes might be present. Since no sequencing data on Israeli HLA-DR1 genes have been reported, we sequenced the first domain (AA 10 91) of the DRB1 gene in 12 DR1-positive Israeli RA patients, 5 healthy controls and a homozygous typing cell (HTC), defining the major Jewish cellular HLA-DR1 subtype. DRB1*0102 (DR1 Dw20) was found in 8 RA patients, 3 controls and the HTC "LVA". DRB1*0101 (DR1 Dw1) was found in 4 RA patients and 2 controls. No other DR1 subtypes were encountered. In all 20 DR1 haplotypes, the DRB1*0101 or 0102 allele was associated with DQA1*0101 and DQB1*0501, being identical to the Caucasian DR1 haplotypes. Thus, at the sequence level, we found no basis for the reported extensive cellular heterogeneity of DR1 in the Israeli population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8456441 TI - HLA-DPB1 alleles correlate with risk for multiple sclerosis in Caucasoid and Cantonese patients lacking the high-risk DQB1*0602 allele. AB - Multiple sclerosis (MS) is a demyelinating disease associated with the HLA-DR2 related haplotype DRB1*1501, DQB1*0602 in Caucasoids and with DQB1*0602 in DR2 positive Cantonese. However, many MS patients do not have the high-risk HLA-D determinants and alternative genes may contribute to the pathogenesis of MS. One candidate gene is HLA-DPB1. Our reanalysis of five earlier reports of HLA-DPB1 antigen distributions in Caucasoid MS patients shows a consistent and highly significant increase (p = 1.5 x 10(-5)) in frequency of HLA-DPw3 in the combined data set. This study tests whether HLA-DPw3 (DPB1*0301) is also increased in frequency in Australian and Cantonese MS patients and whether any distortion in DPB1 allelic distributions can be attributed to linkage disequilibrium with DQB1*0602. PCR-RFLPs were used to determine distributions of 20 HLA-DPB1 alleles in 41 Australian MS patients and 67 controls of known DQB1*0602 status and in 11 Cantonese MS patients and 33 controls positive for HLA-DR2. HLA-DP distributions in Australian MS patients and controls positive for DQB1*0602 did not differ, but in those MS patients lacking DQB1*0602, the DPB1*0301 antigen (phenotype) frequency was significantly (p = 0.006) increased (50.0%) when compared with DQB1*0602-negative controls (9.1%). DPB1*0301 was associated (p = 0.003) with DQB1*0402 (DR8) in Caucasoid MS patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8456442 TI - The occurrence of HLA-B46 in two Caucasoid families. PMID- 8456443 TI - A new DRB1 allele and a novel DR4 haplotype found in a Filipino family. PMID- 8456444 TI - DR "low-resolution" PCR-SSP typing--a correction and an up-date. PMID- 8456445 TI - Production of monoclonal antibodies against Clostridium difficile cytotoxin using immunosorbent binding bioassay procedure. AB - In the following study, a novel screening approach was used to develop monoclonal antibodies specific for toxin B of Clostridium difficile. The approach, which consisted of an immunosorbent binding bioassay (ISBBA), is based on antigen immunocapture by monoclonal antibodies and detection of biological activity. Our results showed ISBBA, which uses unpurified antigen, to be more sensitive than the neutralization assay and ELISA for the detection of toxin B antibody. PMID- 8456446 TI - Proteolytic specificity of moojeni protease A isolated from the venom of Bothrops moojeni. AB - Moojeni protease A, a proteolytic enzyme isolated from Bothrops moojeni venom, hydrolyzes type I collagen, gelatin, fibrinogen, fibrin and the B-chain of oxidized insulin. The proteinase cleaves the A alpha-chain faster than the B beta chain of human fibrinogen and shows no effect on the gamma-chain. Fibrin solubilization appears to occur from the hydrolysis of the alpha-polymer and unpolymerized alpha-chain. The enzyme cleaves the Ala(14)-Leu(15) bond of the oxidized insulin B-chain most rapidly, followed by splitting the Ser(9)-His(10) bond. The Tyr(16)-Leu(17) and Gly(20)-Glu(21) cleavage sites were hydrolyzed slightly more slowly, while the peptide bonds His(5)-Leu(6), His(10)-Leu(11), Glu(21)-Arg(22), Gly(23)-Phe(24) and Phe(24)-Phe(25) were more resistant to the enzyme attack. Small synthetic peptides were not hydrolyzed by moojeni protease A. PMID- 8456447 TI - Multiple toxins in a specimen of the narrow-barred Spanish mackerel, Scomberomorus commersoni. AB - Ciguatoxin-like, scaritoxin-like and other unidentified lipid-soluble toxins were detected in a specimen of Scomberomorus commersoni captured in sub-tropical Queensland. The fish was from a batch that had been involved in human poisonings. The ciguatoxin-like substance made a greater contribution to the total toxicity than did the scaritoxin-like substance. Water-soluble toxins were also present. The most important of these in terms of contribution to total toxicity was unidentified toxic material present in fractions eluted from a silicic acid column with 100% methanol or methanol:water (1:1). After TLC this material yielded a spot positive for alkaloids. Maitotoxin was also detected among the water-soluble toxins. The lethal potency of the fish flesh approximated 27.3 MU/100 g of flesh with water-soluble toxins contributing to a greater extent than the lipid-soluble toxins. (A MU is defined as the minimum amount of toxic material expressed in g required to kill a 20 g mouse within 24 hr after i.p. injection.) The 15 kg fish studied contained a total of approximately 4095 MU. The presence of several water-soluble and lipid-soluble toxins in the fish has implications for the detection of such ciguateric fishes and for the diagnosis and treatment of poisonings stemming from ingestion of these fishes. PMID- 8456448 TI - Behavioural and electroencephalographic effects of Tityus serrulatus scorpion venom in rats. AB - This study was designed to investigate the convulsant effects of T. serrulatus scorpion venom in rats. Pretreatment of rats with venom increased the minimum convulsant dose of picrotoxin, impaired convulsion generalization and displaced to the left the dose-response curve for picrotoxin. It also decreased the intensity but prolonged the duration of seizures caused by pentylenetetrazol injection. Microinjection of the venom into the dorsal hippocampus induced behavioural alterations and epileptiform waves in the EEG. Venom also altered the threshold for, and intensity of, convulsions induced in different experimental models of epilepsy. Different fractions of the venom may be responsible for these different effects. Therefore, purification of venom toxins is necessary for the complete understanding of the present results. PMID- 8456449 TI - Neutralization of pathophysiological manifestations of Russell's viper envenoming by antivenom raised against gamma-irradiated toxoid. AB - Rabbits were immunized against gamma-irradiated (100 krads) Russell's viper venom toxoid adsorbed to aluminium phosphate gel. The antivenom (0.1 ml) neutralized 5 LD50, 8 minimum hemorrhagic doses (MHD) and 14 minimum necrotic doses (MND) of venom. The coagulant and protease activities of the viper venom were neutralized more effectively than phospholipase A activity, by the toxoid antivenom. PMID- 8456450 TI - Effects of Bothrops asper (terciopelo) myotoxin III, a basic phospholipase A2, on liposomes and mouse gastrocnemius muscle. AB - The action of Bothrops asper myotoxin III, a basic phospholipase A2 which induces acute muscle damage, was studied in mouse gastrocnemius muscle in vivo and in vitro and in multilamellar liposomes. Myonecrosis occurred rapidly after myotoxin injection, as indicated by histological alterations and by a drastic increment in plasma creatine kinase levels. A dose-dependent release of creatine kinase from mouse gastrocnemius muscle incubated in vitro with the toxin was observed. Myotoxin III affected negatively charged multilamellar liposomes, as evidenced by the release of peroxidase trapped in the vesicles. In contrast, very little effect was observed on positively charged vesicles. When gastrocnemius muscle or liposomes were incubated at 4 degrees C there was no membrane-disruptive effect. Inhibition of phospholipase A2 activity, by elimination of calcium and addition of EDTA, resulted in a significant, but not total, reduction in both muscle damaging and liposomal disrupting effects. It is proposed that B. asper myotoxin III affects cellular and artificial membranes inducing prominent alterations in membrane permeability to ions and macromolecules. Membrane-disrupting activity is probably related to a molecular region different from the catalytic site, although enzymatic activity greatly enhances myotoxin action. PMID- 8456451 TI - Tityus serrulatus scorpion venom toxins display a complex pattern of antigenic reactivity. AB - The antigenic properties of alpha-type and beta-type toxins purified from Tityus serrulatus (Ts) venom were analysed by radioimmunoassay, using rabbit antibodies raised against Ts VII, the main beta-type toxin in the venom, and against Ts IV, an alpha-type toxin. The anti-Ts VII serum did not recognize either the other beta-toxins Ts I and Ts II or the alpha-toxin Ts IV; the anti-Ts IV serum did not bind any of the three beta-toxins Ts I, Ts II or Ts VII. Thus, Tityus toxins display at least three distinct antigenic reactivity patterns. PMID- 8456452 TI - OR nursing and environmental ethics. Medical waste reduction, reuse, and recycling. AB - Health care workers have an important opportunity to manage the environmental effects of their practice. Their efforts may seem small, but each step builds a base of sound behaviors and thinking that are necessary for the success of the whole. Starting a hospital recycling program is difficult. The five key steps are find out what exists, survey your needs, survey local recycling agencies, educate your staff, and communicate your progress. Nursing is a powerful organization with a strong educational, research, and communication base. By raising the level of awareness, reducing, reusing, recycling, and working with others, nurses can look toward achieving a larger vision of a healthy planet. PMID- 8456453 TI - Breast augmentation mammoplasty. Preoperative and postoperative nursing care. AB - Breast augmentation mammoplasty is a vital part of reconstructive breast surgery. More than 2 million women over the past 30 years have undergone this type of surgery either for reconstruction or augmentation. There continues to be a need for further investigation of the human biological response to these devices. Safety of breast implants is currently a major factor under investigation. There are important preoperative and postoperative considerations of which the nurse should be aware. Quality preoperative and postoperative nursing care and intervention also play an important role in ensuring the best outcome for breast augmentation mammoplasty patients. PMID- 8456454 TI - When nurses cry. AB - During a typical work day, nurses encounter situations of grief, death, and crisis that increase vulnerability to crying. Because of the social and cultural bias against crying, nurses may try to control crying and may feel uncomfortable and embarrassed if unable to do so. Nursing has moved toward a more people oriented approach, and there is more openness toward expressing feelings. However, nurses are still expected to remain in control of their emotions. Crying may have a profound therapeutic effect in helping persons deal with overwhelming emotions. In selective situations, showing genuine emotion can be a meaningful way to provide emotional support. PMID- 8456455 TI - Laparoscopic bowel resection. AB - Patient selection for laparoscopic colon surgery is a crucial factor in the success of the operation. Ideally, the underlying pathological process requiring an operation should be benign. Patients undergoing laparoscopic colon surgery are prepared preoperatively as for conventional laparotomy. However, problems may be encountered in positioning the patient because the procedure requires that the OR bed be rotated laterally and using Trendelenberg positions. Potential advantages of laparoscopic colon surgery primarily concern improved pain control and a shortened recovery period. However, the procedure takes longer to complete and overall costs may be higher. PMID- 8456456 TI - The cost of saving the environment. PMID- 8456457 TI - When one group member "knows it all". AB - One of the most difficult aspects of leading a discussion and trying to facilitate group problem solving is restraining domineering group members. A group leader who cannot control aggressive, talkative individuals will soon have a group where members are not only angry and frustrated, but also who will make excuses to be excluded or who will leave the group. PMID- 8456458 TI - Restore our professionalism. PMID- 8456459 TI - Managing change in a changing environment. AB - Change comes from different directions and must be managed in different ways. Change may come from the top down (eg, from parents to children) or from the bottom up (eg, from staff to management). Introduced change is initiated by you; imposed change is initiated by someone else. Change is necessary to move forward and remain effective. If change is resisted, there is the risk of becoming complacent, outdated, or obsolete. There is no room for obsolescence in health care. Even under the best of circumstances, change will be met with resistance. To overcome resistance, involve people in planning for the change and ensure understanding through verbal and written communications. Be prepared to revise the plan, and always remain flexible. PMID- 8456460 TI - Induction of long-term specific tolerance to allografts in rats by therapy with an anti-CD3-like monoclonal antibody. AB - Monoclonal antibodies to CD3 have been shown to activate T cells in vivo and in vitro but have also been shown to render T cells anergic in vitro. In this study G4.18, a mouse IgG3 mAb, was produced that appeared to recognize CD3 by its binding to all peripheral T cells, including a population not recognized by mAb to TCR-alpha/beta that was presumed to be TCR-gamma/delta cells. It precipitated molecules in the 24-26 kd region consistent with the CD3 complex as well as molecules approximately 45 and approximately 49 kd that corresponded to TCR alpha and beta chains and a 92-kd complex. Incubating T cells for 24 hr with saturating concentrations of G4.18 caused modulation of the TCR complex. In vitro, it activated T cells but only if prebound to plastic. In solution it inhibited MLC and CML, but not PHA or Con A activation. In vivo, G4.18 was not toxic even in high doses, and this was thought to be due to the inability of this mAb to activate T cells in vitro because the rat lacks Fc receptors for mouse IgG3. Therapy with G4.18 resulted in transient modulation of TCR/CD3 on T cells and depletion of these cells from blood. G4.18 had no depleting effects by lymph node or spleen cells but caused marked, transient thymic involution. Therapy with G4.18 also induced indefinite survival (> 100 days) of PVG (RTIc) heart grafts but not skin grafts in DA (RTIa) hosts. These hosts with long-surviving cardiac transplants, when grafted from PVG skin, accepted these grafts but rejected third party skin in first-set. Thus G4.18 was shown to induce long-term specific tolerance to an organ allograft. PMID- 8456461 TI - Energy-dependent injury to cultured sinusoidal endothelial cells of the rat liver in UW solution. AB - The critical injury to liver during cold preservation is believed to occur to the sinusoidal endothelium. In this study the viability of cultured sinusoidal endothelial cells from rat liver was assessed during storage in University of Wisconsin solution at 4 degrees C. The vast majority of cells (83 +/- 12%) died within 24 hr of storage. Addition of KCN (1 mM) to the solution to simulate hypoxia markedly increased survival: only 3 +/- 2% of cells had lost viability after 24 hr in the presence of cyanide. Further experiments showed that other inhibitors of mitochondrial ATP formation (antimycin A 1 microM, rotenone 1 microM, oligomycin 10 microM, carbonyl cyanide m-chlorophenylhydrazone 1 microM) were protective as well, whereas glucose (10 mM) greatly diminished the protective effect of cyanide (loss of viability 38 +/- 7% after 24 hr). ATP measurements confirmed the correlation between the energy state of the cells and cell death: ATP levels after 6 hr of incubation were 19.9 +/- 4.0 nmol/10(6) cells in UW solution, 13.7 +/- 2.9 nmol/10(6) cells in UW + glucose, 6.9 +/- 1.9 nmol/10(6) cells in UW + KCN + glucose and 1.9 +/- 1.5 nmol/10(6) cells in UW + KCN. In contrast to the protective effect observed in UW solution, addition of KCN to Krebs-Henseleit buffer led to increased endothelial cell damage upon cold storage. We therefore conclude that in UW solution damage to the sinusoidal endothelium is energy-dependent. PMID- 8456462 TI - The influence of thyroid hormone replacement in a porcine brain death model. AB - This study was conducted to determine whether the administration of tri iodothyronine (T3) to brain-dead donor pigs would improve hemodynamic instability, serum levels of thyroid hormones, or the outcome of transplantation of donor livers. Brain death was caused in young pigs (25-38 kg) by rapid inflation of an intracranially implanted balloon catheter. The animals were maintained on a ventilator and frequent measurements of acid/base balance, electrolytes, and glucose were made. At the end of 16 hr, livers were removed and implanted into prepared recipients. Serum-free tri-iodothyronine fell to zero at the end of 16 hr, and there was a 4-6-fold decline in free thyroxine (T4). The levels of serum reverse T3 (rT3) however, increased up to 6-fold. In animals treated with tri-iodothyronine 2 micrograms/hr, the serum levels of free T3 and T4 were not changed but the levels of serum reverse T3 (rT3) increased further. There were no apparent correlations between any hemodynamic parameter and serum thyroid hormone levels in the donors. After the liver transplants, recipients could be divided into those that survived longer than 6 days and those that did not. Although there were significant differences in the plasma levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase, there was no correlation between survival and whether the donor had received tri iodothyronine. Although other hormones, including insulin and cortisol, may also be necessary, there is no indication from these studies that the administration of tri-iodothyronine to brain-dead donors of liver grafts benefits the serum hormone levels in the donors or the subsequent survival of the recipients. PMID- 8456463 TI - Recovery of hyaluronan during perfusion of small bowel transplantation reflects rejection. AB - Rejection seen after small bowel transplantation (SBT) in the rat is associated with an accumulation of hyaluronan (HA) in the lamina propria of the graft. In this study the intestinal intraluminal content of this connective tissue component was measured in order to determine if HA could be used as an index of rejection following SBT. Syngeneically and semiallogeneically transplanted rats were investigated by perfusion of a 4-cm segment of the intestinal graft on days 2, 4, and 6 posttransplantation. The amounts of HA recovered during perfusion were analyzed using a radiometric assay. In rejecting grafts the recovered HA amounts increased 15 times from day 2 to day 6, although after syngeneic transplantation there was only a minor increase from day 2 to day 4 and no further increase on day 6. Thus, the recovery of HA during perfusion of transplanted small bowel grafts has the potential value to reflect rejection. PMID- 8456464 TI - Cytoimmunologic monitoring using DNA analysis in canine liver transplantation. AB - In this experiment, we evaluated the significance of flow cytometric DNA content measurement of circulating blood mononuclear cells in early detection of canine hepatic allograft rejection. In nonimmunosuppressed controls, the SG2M% of blood mononuclear cells significantly increased on days 5-6 after liver transplantation compared with the pretransplant values (P < 0.01). At the time of SG2M% elevation, microscopic examination of the graft revealed acute mild rejection. These changes in SG2M% and histological findings were observed one or two days earlier than biochemical changes indicative of liver injury. On the other hand, nonrejected cases under sufficient immunosuppression with cyclosporine or FK506 maintained low levels of SG2M% in comparison with the pretransplant values (P < 0.05). The rejecting cases under insufficient immunosuppression showed significantly elevated SG2M% (P < 0.05), and successful steroid pulse therapy provided to the recipients immediate normalization of SG2M% with histological restoration. Moreover, other complications such as pulmonary infection, peritonitis, and marasmus--rather than the rejection reaction--did not influence on SG2M%. These results led us to believe that flow cytometric DNA content measurement of blood mononuclear cells provides relevant and early information with respect to ongoing canine hepatic allograft rejection. The diagnostic value for differentiation between hepatic allograft rejection and infection of the transplant by hepatitic viruses needs further evaluation. PMID- 8456465 TI - Evidence that an anthracycline-anti-CD8 immunoconjugate, idarubicin-anti-Ly-2.1, prolongs heart allograft survival in mice. AB - To examine the potential use of immunoconjugates of drugs and antibodies as immunosuppressive agents, mice were treated with a short course (4 days) of T cell-specific anti-Ly-2.1 monoclonal antibody, or MAB conjugated to an anthracycline, idarubicin (IDA). The anti-Ly-2.1 MAB had no significant effect on the survival of BALB/c (Ly-2.2) heart allografts in CBA (Ly-2.1) mice, but was a potent immunosuppressive agent when coupled to IDA, with most grafts surviving for > 100 days following treatment with doses ranging from 10 to 120 micrograms IDA, covalently coupled to 1-8 mg MAB. IDA-MAB treated mice with long-surviving heart grafts showed donor-specific tolerance. They did not reject donor-type skin grafts (these survived for > 50 days), but rejected third-party skin in 10-14 days. Heart allografts in these mice survived for > 100 days. Allografts placed 30 days after treatment were rejected, showing a recovery of peripheral T cell function at this time. Newly derived thymic T cells were, however, not required for this recovery since adult thymectomized, IDA-MAB treated animals also recovered T cell function and rejected heart allografts. FACScan analysis of T cells from mice treated with 80 micrograms IDA-4 mg MAB, which had received a heart allograft, showed 95% T cell depletion in the spleen compared with ungrafted, IDA-MAB treated animals, and untreated controls with or without allografts. Splenic T cell depletion was however not significant in CBA mice immunosuppressed with the lower dose of 10 micrograms IDA-MAB. Thus rapid depletion of splenic T cells was not required for immunosuppression induced by IDA-MAB conjugates. However, the minor subpopulation of Ly-2+, which was activated by alloantigen while carrying IDA-MAB, may be depleted during the T cell response to the allograft, resulting in a state of alloantigen-specific tolerance in mice with long-surviving heart allografts. PMID- 8456466 TI - The effects of intraoperative administration of OKT3 during renal transplantation. AB - The use of the monoclonal antibody OKT3 for induction immunosuppression in renal transplantation is increasing--however, the safety of intraoperative administration continues to be questioned because of first-dose effects. The current study was designed to examine the effects of intraoperative administration of OKT3 on the cardiovascular and pulmonary systems in 161 consecutive renal transplant recipients. Patients receiving OKT3 intraoperatively during renal transplant (99 cadaver recipients) were compared with 62 patients not administered the drug (31 cadaver, 25 living-related-donor, 6 living nonrelated donor). Intraoperative airway pressure (highest, average), O2 saturation (SaO2), temperature, blood pressure changes, cardiac rhythm, and bronchospasm were compared in these two groups. Significant physiologic changes noted in the group receiving OKT3 included increased temperature (both intraoperative and postoperative), decreased SaO2 (postoperative), and increased FiO2 (postoperative). Despite these differences, no clinically significant changes were noted in the group receiving OKT3. OKT3 induction given at the time of surgery was associated with a significantly increased one- and three-year graft function. This study demonstrates that first-dose administration of OKT3 intraoperatively during renal transplantation is safe and effective. PMID- 8456467 TI - Long-term consequences of different immunosuppressive regimens for renal allografts. AB - The long-term effects of four different immunosuppressive regimens on renal allografts have been investigated up to four years. A total of 128 recipients of first cadaveric renal allograft were randomized, after an initial induction period, to receive either triple drug therapy--i.e., (low-dose) cyclosporine, azathioprine, and methylprednisolone, or any possible combination of two drugs- i.e., Aza plus CsA, Aza plus MP, and CsA plus MP. The actual four-year graft survival rates for the triple therapy, Aza plus CsA, Aza plus MP, and CsA plus MP groups were 72%, 69%, 75%, and 59%, and patient survival rates were 78%, 81%, 81%, and 84%, respectively, with no significant differences. The cumulative number of chronic rejections up to 4 years was 0.09, 0.29, 0.25, and 0.34 per patient per group (P = ns), respectively. At 2, 3, and 4 years posttransplantation, the graft function was significantly worse in the Aza plus MP group compared with the triple therapy group (P < .05). Of the 98 patients who did not have type I or II diabetes at the time of transplantation, 17 developed posttransplantation diabetes mellitus or an abnormal glucose tolerance test within 2 years posttransplantation. All these patients had received steroids and none of the patients without steroids had these abnormalities. At two years the mean cholesterol level was highest in the Aza plus MP group, 6.8 mmol/L and lowest in the group receiving triple therapy, 5.8 mmol/L (P = ns). The use of (low-dose) CsA was not associated with lipid abnormalities or with disturbances in glucose metabolism. A protocol graft biopsy was performed at two years on all functioning kidneys, and the histological changes were scored blindly. No CsA specific changes, except isometric vacuolation in tubuli, were found. Histological alterations characteristic of chronic rejection were expressed as "chronic allograft damage index." Chronic allograft damage index was lowest in the triple therapy group, 1.5, compared with the other groups, 3.2-4.3 (P = .01), indicating the least histopathological change in the triple therapy group. In conclusion, this long-term study did not show any serious cyclosporine-related side-effects when used in low dose in combination with two other drugs. Some side effects, such as posttransplant diabetes mellitus and probably some lipid abnormalities, could rather be traced to a higher dose of steroids. Moreover, the triple drug therapy was more efficacious than any double drug regimen in the prevention of chronic histological changes in renal allografts. PMID- 8456468 TI - Oxygen free radicals and platelet and granulocyte aggregability in renal transplant patients. AB - Oxygen free radical reaction products (plasma malondialdehyde), the free radical scavengers plasma thiol and red cell superoxide dismutase (SOD), and whole blood platelet and granulocyte aggregation were measured in 23 renal transplant patients and 23 age-matched controls. Malondialdehyde-like material (MDA) was significantly increased in transplant patients compared with controls (transplants MDA [median, range], 7.7 [5.3-11.5] nmol/ml; controls MDA, 6.3 [5.4 8.7] nmol/ml; P < 0.001). The patients also had increased red cell superoxide dismutase (transplants SOD, 128.1 [89.4-93.8] U/0.5 ml red cells; controls SOD, 95.9 [62.0-132.6] U/0.5 ml red cells; P < 0.001) and reduced plasma thiol (transplants thiol, 428 [266-496] mumol/L; controls thiol, 445 [358-501] mumol/L; P < 0.05). These factors were not influenced by immunosuppressive therapy, duration of transplantation, or creatinine concentration. Transplant patients had significantly higher levels of collagen-induced and spontaneous whole blood platelet aggregation compared with controls (collagen: transplants, 72 [4-93%]; controls 43 [6-94]%; P < 0.001; spontaneous: transplants 46 [11-93]%; controls 37 [10-75]%; P < 0.05). Spontaneous platelet aggregation, however, was significantly correlated with creatinine concentration (r = 0.525, P < 0.02, Spearman's correlation), and was raised only in those patients with a degree of renal impairment. Granulocyte aggregation was increased in patients receiving cyclosporine (CsA [n = 15], 57 [36-66]%; no cyclosporine [n = 8], 45 [37-62]%; controls [n = 23]; 39 [31-61]%; P = 0.004). Renal transplant patients are subject to oxidative cell damage, and may be at increased risk of vascular thrombosis. Possible contributory factors include an immunological reaction to the graft and/or the effects of immunosuppressive therapy. PMID- 8456469 TI - 15-Deoxyspergualin "rescue therapy" for methylprednisolone-resistant rejection of renal transplants as compared with anti-T cell monoclonal antibody (OKT3). AB - A randomized trial with OKT3, an anti-T cell monoclonal antibody or with 15 deoxyspergualin against methylprednisolone-resistant rejection crisis was performed in 25 posttransplant patients immunosuppressed with prednisolone and cyclosporine. At least temporary reversal of rejection was observed in 58.3% of patients treated with 15-deoxyspergualin. This reversal rate may be quite comparable to 61.5% seen in patients treated with OKT3. Adverse effects with 15 deoxyspergualin were related to bone marrow suppression, while those with OKT3 were pyrexia, gastrointestinal symptoms, and herpes infection. In contrast to OKT3, which may act by modulating T cell surface antigen, 15-deoxyspergualin may be effective somewhere in the later stages of the rejection cascade. PMID- 8456470 TI - Computer analysis of cadaver kidney allocation procedures. AB - Data of 32,000 donors were utilized for a computer simulation to analyze the effect of selection parameters on the outcome of kidney transplants. If the HLA match grade is considered for organ allocation, the overall 1-year graft survival rate is up to 7% higher for first cadaver transplants and up to 12% higher for second transplants than if HLA matching is disregarded. This solely success oriented organ allocation method, however, leads to prolonged waiting times for patients with rare HLA phenotypes. We developed a selection procedure that yields results near the theoretical optimum: 95% of all patients can be transplanted with 0-2 HLA-A, -B, -DR antigen mismatches, the average waiting time decreases to 20 months, and no patient needs to wait longer for a transplant than 6 years. The overall graft survival rate is only 0.4% lower than the rate obtainable with strictly HLA-oriented allocation. The method prevents "poorly matchable" patients from accumulating on the waiting list. Additionally, the unfavorable race ratio in the North American recipient pool can be largely normalized. PMID- 8456471 TI - Arterial ketone body ratio in pediatric liver transplantation. AB - Arterial ketone body ratio (AKBR) was measured serially in 49 pediatric orthotopic liver transplantations. The AKBR pattern correlated with hepatic synthetic function, as well as with short-term graft and patient survival. A rapid recovery pattern of AKBR to above 1.0 within 40 hr after reperfusion was associated with 94% graft and patient survival. Pediatric liver grafts were found to have better tolerance to low energy levels when compared with previously published data for adult OLT. The salvage rate of pediatric grafts exhibiting a slow recovery pattern (AKBR 0.7-1.0) was 71%. No recovery pattern (AKBR < 0.7) was seen in all 6 cases of primary nonfunction, and in 3 of 4 cases of early hepatic artery thrombosis (HAT). All these grafts were lost; however, 56% of the children in this group survived retransplantation. Unlike the PNF grafts, the no recovery pattern after HAT was characterized by gradual improvement of the synthetic function, despite the low energy state. PMID- 8456472 TI - Systemic versus nonsystemic reperfusion of the transplanted liver. AB - Reperfusion of the orthotopically transplanted liver can result in severe hemodynamic instability. This instability can result in the postreperfusion syndrome (PRS), which includes decreases in mean arterial pressure (MAP), systemic vascular resistance (SVR), and heart rate, and increases in central venous pressure and pulmonary capillary wedge pressure. This syndrome appears to be mediated by the left ventricular mechanoreceptor reflex (LVMRR), which can be activated by changes in preload, afterload, or left ventricular contractility, and by the infusion of alkaloids or potassium into the right atrium. In an attempt to prevent activation of the LVMRR and PRS, we have inserted a cannula into the retrohepatic vena cava and have allowed the initial 500-600 cc of portal blood reperfusing hepatic allografts to be discarded. We compared this nonsystemic reperfusion (NSRP) of livers with systemic reperfusion (SRP), in which the initial portal blood reperfusing livers is allowed to enter the systemic circulation. In the NSRP group (n = 14) there was no decrease in MAP, heart rate, or SVR, and the serum potassium did not increase after reperfusion. In the SRP group (n = 14), six patients (42%) developed PRS and there were statistically significant decreases in MAP and SVR, and increases in pulmonary capillary wedge pressure and serum potassium, as compared with the NSRP group. In conclusion, NSRP results in less hemodynamic instability during reperfusion, and should be considered the preferred method for reperfusion of the transplanted liver. PMID- 8456473 TI - Acute liver allograft rejection--is treatment always necessary? AB - A group of 195 consecutive adult patients who received a primary orthotopic liver allograft were reviewed retrospectively to analyze the incidence of rejection, the response to antirejection therapy, and the impact of acute rejection on the development of ductopenic rejection. The diagnosis of acute rejection (AR) was based on a combination of clinical and histological criteria, and 69.7% of the patients had at least one episode of acute rejection. Only 6.7% of the patients failed to respond to steroids and were treated with OKT3. Four (2.3%) patients developed acute vanishing bile duct syndrome (within 60 days) and 6 (3.5%) patients developed chronic rejection. Eight patients who spontaneously recovered from AR without additional immunosuppression are described in detail. In addition to histological damage, all developed significant hepatic dysfunction. Except for one patient who died from disseminated fungal infection, the 7 remaining patients are alive with excellent graft function 7 to 21 months posttransplant. While severe AR and recurrent AR should be treated without delay, some patients with mild-to-moderate rejection and hepatic dysfunction may resolve without additional immunosuppression. PMID- 8456474 TI - Monoclonal antibodies in prophylactic immunosuppression after liver transplantation. A randomized controlled trial comparing OKT3 and anti-IL-2 receptor monoclonal antibody LO-Tact-1. AB - A prospective trial was conducted to assess the efficacy of induction immunosuppression with antilymphocyte monoclonal antibodies in 129 primary liver transplant patients who were randomly divided into three groups according to immunosuppression during the first 10 days post-OLT: triple drug therapy only (TDIS: cyclosporine, steroids, azathioprine) (group I: n = 42); TDIS with a 10 day course of OKT3 (group II: n = 44); and LO-Tact-1 (anti-IL-2 receptor mAb) (group III: n = 43). Biopsy-proved acute rejection (AR) was treated using the same biopsy-guided protocol in the 3 groups. One-year patient survival rates were 67%, 84%, and 93% in groups I, II, and III, respectively (I vs. II, NS; I vs. III, P = 0.001; II vs. III, P = 0.044). Incidences of AR were studied in the subgroup of 100 patients who were exposed to the risk of developing rejection, with an overall rate of 89% during the first 3 months post-OLT, similar in the 3 groups. However, incidences of steroid-resistant rejection diagnosed during the 10 first days post-OLT were 54%, 24%, and 34% in groups I, II, and III and 46%, 26%, and 11%, respectively, during the 10-90 days interval. Sixteen patients with CMV had received OKT3, whereas the 5 remaining CMV cases had not (P = 0.019). In summary: (1) mAbs did not modify crude incidence of AR; (2) in the early period (< 10 days), TDIS immunoprophylaxis combined with OKT3 was more efficient than TDIS alone; (3) when compared with groups I and II, LO-Tact-1 apparently better prevented steroid-resistant rejection during the 10-90 days post-OLT; (4) OKT3 significantly increased incidence of CMV infection. In conclusion, TDIS with LO Tact-1 seemed to achieve the better risk-benefit ratio in induction immunosuppression after OLT. PMID- 8456475 TI - Potential availability of transplantable organs and tissues in fatalities from injury and nontraumatic intracranial hemorrhage. AB - Study of all Vermont and urban Rhode Island trauma fatalities for 1987, and all fatalities in these states from nontraumatic intracranial hemorrhage for 1986 and 1987, identified few potential donors for asystole-sensitive organs, such as heart, lungs, liver, pancreas, and kidneys. It is estimated that nationally there is a maximum potential of about 5000 cadavers per year from these two sources that meet screening criteria for age, duration of survival after event, brain death, and absence of organ damage or important disease. This would yield up to 5000 hearts, livers, and pancreases, perhaps 5-6000 lungs, and up to 10,000 kidneys. However, for tissues that have longer postdeath viability it is estimated that annually at least 60,000 eyes, 22,000 heart valve sets, 29,000 donations of 2 or more long bones per cadaver, and 36,000 skin donations are potentially available from these sources. PMID- 8456476 TI - Extended follow-up in 212 long-term allogeneic bone marrow transplant survivors. Issues of quality of life. AB - A group of 235 allogeneic marrow recipients were contacted at least one year following their BMT to obtain information on their quality of life; 212 (90%) agreed to participate in this survey. A total of 162 adults and 50 pediatric survivors were interviewed during clinic visits (5%) or over the telephone (95%). Changes in productive activity and marital status at the time of interview were studied, as well as the presence of physical symptoms and perception of a general sense of well-being. Older transplant recipients were observed to have a significantly higher incidence of chronic graft-versus-host disease, common colds, and skin changes when compared with pediatric transplant recipients (P < 0.01). Older subjects were also more likely to require any type of regular medication. Younger survivors were rated with a higher Karnofsky performance status and global subjective score. There were no significant differences between patients who received TBI as part of the conditioning regimen and those who did not, with the exception of increased cataract development in pediatric patients receiving TBI (P < 0.008). We conclude that most allogeneic marrow transplant survivors, especially those individuals of younger age at the time of their transplants, are doing well in the domains tested. PMID- 8456477 TI - Lung transplantation in patients over the age of 50. AB - It is common to assign an upper age limit for potential lung transplant recipients. The influence of age on LTX outcome is, however not, documented. A review of our first 103 LTXs, 51 single LTXs and 52 double LTXs, includes 31 recipients aged 50-63 years (mean 55.3 +/- 3.9); 19 received single LTX, and 12 received double LTX. Indications for LTX in those aged greater than 50 included proportionately more patients with emphysema and interstitial lung disease. Actuarial survivals in those aged less than 50 at 12, 36, and 60 months were 68%, 60%, and 55%, and in those aged greater than 50 was 70%, 61%, and 61%, respectively. The causes of death reflect a tendency of younger patients to die from graft rejection and older patients to die from sepsis. Acute rejection more than 6 weeks posttransplant and chronic rejection were less frequent in older patients (P < 0.05). The 6-minute walk and modified Bruce protocol tests, the incidence of CMV pneumonitis, and the late post-LTX renal function were not related to age. In conclusion, in carefully selected candidates in their sixth and seventh decades, LTX is an acceptable operation for end-stage lung disease. The tendency of older patients to a lower incidence of late allograft rejection (acute or chronic) may reflect decreased immunological responsiveness with age. PMID- 8456478 TI - The reflush effect--a prospective analysis of late perfusion. AB - This prospective randomized trial examines the effect of a "reflush" with preservation solution immediately prior to renal allograft implantation, using hyperosmolar citrate (HOC, n = 10) or phosphate-buffered sucrose (PBS140, n = 10) versus no reflush (n = 10). All kidneys had been stored in HOC. The HOC reflush did not alter the postpreservation intra- or extracellular electrolyte milieu, whereas the PBS140 reflush resulted in an apparent overall loss of both sodium and potassium from the kidney (P < 0.0005). A small amount of calcium was released into the venous effluent in both reflush groups. A similar amount of lactic acid was released into the venous effluent of the two reflush groups, reflected by a lower pH (P < 0.0005), and there was a similar loss of lactate dehydrogenase and creatine phosphokinase. An analysis of procoagulant activity in the first urine produced was performed as a marker of reperfusion injury. The median value was higher in the No Reflush group at 457.5 units, compared with 263.0 and 209.0 units for the PBS140 and HOC Reflush groups, respectively (P = 0.06). Reflushing the kidneys reduced the postoperative dialysis requirement (from 40% to 15%), but by the end of the first posttransplant week there was no significant difference between the renal functional analyses of the three groups, and there was no difference at one year. The proposed mechanism for the early renal functional improvement is a reduction in the calcium paradox and free radical formation, by release of calcium and ATP breakdown products into the venous effluent prior to implantation. PMID- 8456479 TI - Nitric oxide production by mouse sponge matrix allograft-infiltrating cells. Comparison with the rat species. AB - We have recently demonstrated in the rat species that sponge matrix allograft infiltrating cells spontaneously produce nitric oxide (.N = 0) and this .N = 0 production precedes the development of CTL. Compared with our experience in the mouse species, the CTL activity recovered from rat sponge grafts is of shorter duration and less intense. Assessment of the spontaneous .N = 0 production by mouse allograft infiltrating cells reveals a more delayed time course of production, paralleling the recovery of CTL activity from the graft. The in vitro spontaneous .N = 0 production by mouse allograft-infiltrating cells was greater than the production by syngeneic graft-infiltrating cells on all days tested. Exposure of allogeneic but not syngeneic graft infiltrating cells to the sensitizing alloantigen in vitro resulted in enhanced .N = 0 synthesis. In contrast, LPS stimulated .N = 0 production by both syngeneic and allogeneic graft cells on all days postgrafting. Culture of day-14 allograft infiltrating cells with alloantigen in the absence of NG-monomethyl-L-arginine (NMA), the competitive inhibitor of .N = 0 synthesis, resulted in elevated supernatant NO2- levels and decreased 3H-TdR uptake and CTL activity compared with cultures carried out in the presence of NMA. The supernatant NO2- levels, as well as the CTL activity and 3H-TdR incorporation of the cultured cells, was dependent on the concentration of NMA present, and these effects could be reversed by excess L arginine. Thus, the species difference in .N = 0 synthesis (rat > mouse), observed by others, is evident in the sponge allograft model and may explain why CTL activity recovered from rat allografts is of shorter duration and less intense than that from the mouse allografts. PMID- 8456480 TI - The effect of chronic graft-versus-host disease on B cell development. AB - Chronic graft-versus-host disease often results in a combined deficiency of humoral and cell-mediated immunity. Clinical and experimental studies have suggested that the decrease in B cell responsiveness is due to a failure of B cell production in the bone marrow, intrinsic B cell defects, excessive suppressor T cell activity, and deficient T helper activity. In the present study, we analyze the basis of B cell immunodeficiency in C.B-20-->(C.B-20 x B10.D2)F1 animals afflicted with chronic GVHD. The initial decline in B cell production in the BM accounts for the early reduction in the number of B cells in the spleen and BM. Later, as B cells appear in near-normal numbers in the BM, the spleen and lymph node are repopulated by the newly derived B cells. Associated with the appearance of B cells in the BM and spleen is the ability to respond to lipopolysaccharide. In contrast, both B cell populations are severely diminished in their ability to proliferate in response to agar-derived mitogens to form colonies (CFU-B). The reduction in the CFU-B response is most likely a consequence of an inherent B cell defect, since purification of C.B-20-->F1 splenic B cells does not restore the colony-forming potential. Unlike BM and splenic B cells, LN B cells are unable to respond to either mitogen. Taken together, these results imply that a population of B cells derived from a distinct lineage and/or B cell maturation is defective in mice undergoing GVHD. PMID- 8456481 TI - Cryopreserved microencapsulated hepatocytes--transplantation studies in Gunn rats. AB - Hepatocyte transplantation has been shown to provide significant metabolic support in several animal models of liver diseases. However, for it to be a viable alternative for supplementation of liver function in disease, large quantities of isolated hepatocytes would be necessary. At the present time there are no inexpensive routine methods for cryopreservation of hepatocytes. Existing procedures are cumbersome and require expensive programmable freezers. Hepatocyte cultures are sensitive and easily damaged in handling. By utilizing techniques of microencapsulation and cryopreservation we have attempted to overcome these problems. We have developed a simple, convenient, and inexpensive technique for the long-term storage of hepatocytes. Biological activity of the nonfrozen isolated encapsulated hepatocytes (IEH) and cryopreserved IEH (cIEH) was assessed both in tissue culture and by transplantation in Gunn rats. Significant urea and protein syntheses were detectable during the 10-day culture period even in the 30 day cIEH. Additionally, transplanted IEH and cIEH significantly reduced hyperbilirubinemia in Gunn rats for up to 30 days posttransplantation. Control (empty) microcapsules did not lower serum bilirubin levels. Thus we conclude: (1) cryopreservation of IEH is a convenient and cost-effective method for preserving and storing hepatocytes; (2) cryopreserved IEH function as well as nonfrozen IEH both in vitro and in vivo; (3) microencapsulation may protect hepatocytes from the adverse effects of cryopreservation. PMID- 8456482 TI - A comparison of the immunosuppressive effects of cyclosporine A and cyclosporine G in vivo and in vitro. AB - In this study we compared the immunosuppressive effects of cyclosporine (Cs) A and G, both in vitro (human and rabbit) and in vivo (rabbit). The 50% inhibitory concentration (IC50) of CsG was up to three times greater than that of CsA for mitogen and alloantigen-induced lymphocyte proliferation (IC50 CsA 1 degree MLC = 19 +/- 4 micrograms/L vs. IC50 CsG = 60 +/- 7 micrograms/L; P < 0.01). Kinetic studies in both human and rabbit systems showed that the effectiveness of both drugs was similarly reduced when added at later times after culture initiation. The effects of CsA and CsG in combination on immune responses appeared to be antagonistic at higher and additive at lower drug doses. We also compared the ability of CsA and CsG to displace 3H-CsA from PBMC. The 50% displacement concentration (DC50) for CsG was up to three times greater than that for CsA (DC50 CsA = 1.44 +/- 2.49 x 10(-7) M vs. DC50 CsG = 3.9 +/- 5.4 x 10(-7) M; P < 0.05), suggesting that CsG does not bind as well to PBMC as CsA. In vivo studies using skin allografts confirmed in vitro findings. Both CsA and CsG at 5 and 10 mg/kg/day significantly (P < 0.01) prolonged graft survival compared with control animals. However, at these doses and even at 15 mg/kg/day CsG, CsA was more efficacious at prolonging skin graft survival in rabbits (P < 0.01), e.g., mean survival time (MST, days) 10 mg/kg/day CsA = > 20.5 vs. MST 15 mg/kg/day CsG = 15.0. These results suggest that both in vitro and in vivo in rabbits CsG is less immunosuppressive than CsA. PMID- 8456483 TI - An increase in cytosolic protease activity during liver preservation. Inhibition by glutathione and glycine. AB - Degradative cytosolic proteolysis contributes to cell injury following ATP depletion. Although ATP depletion is a salient feature of ischemic liver storage for transplantation, information regarding cytosolic protease activity during liver storage is lacking. Thus our aim was to measure liver cytosolic protease activity following ischemic storage. A progressive increase in total cytosolic protease activity was observed over time at both 37 degrees C and 4 degrees C, but the increase was greater at 37 degrees C. Total cellular proteolysis was also temperature-dependent during anoxia (37 degrees C > 4 degrees C), demonstrating a physiologic correlation between cellular proteolysis and measurements of cytosolic protease activity. The stimulation of total cytosolic protease activity was due to an increase in metallo- and aspartate protease activity. Of particular interest, glutathione (GSH) inhibited both metalloprotease and aspartate protease activity from cytosol of stored livers. Glycine, the carboxyl-terminal amino acid of GSH, also inhibited both metalloprotease and aspartate protease activity. In addition to being an antioxidant, GSH may exert its protective effects during organ preservation by inhibiting cytosolic proteases--perhaps via its glycine moiety. These experiments support the hypothesis that degradative proteolysis contributes to liver injury during organ preservation. PMID- 8456484 TI - Induction of prolonged tolerance to third-party skin grafts following fully allogeneic bone marrow transplantation in mice. AB - Fully allogeneic C57BL/6-->BALB/c chimeras were grafted at different intervals after bone marrow transplantation with C3H/HeJ skin grafts. We found that the donor-type and host-type skin grafts were always permanently accepted by the allogeneic chimeras, whereas the acceptance or rejection of third-party grafts was dependent on the timing of skin grafting: if grafted later then 3.5 weeks after BMT, they were rejected; if grafted earlier they were accepted for prolonged periods (over 100 days). We further show that 77% of the C57BL/6- >BALB/c chimeras that had been grafted with C3H/HeJ skin within the first 2 weeks post-BMT were still holding the graft 15 weeks after transplantation, as opposed to 11% of the chimeras that had been grafted 8.5 weeks post-BMT. Syngeneic BALB/c ->BALB/c chimeras, in contrast to allogeneic chimeras, promptly rejected the third-party skin grafts even when these grafts were placed within the first 3 weeks after BMT. Thymocytes and splenocytes from allogeneic chimeras that accepted the third-party skin grafts were able to mount relatively strong mixed lymphocytes reactions against the third-party antigens. Grafting of secondary skin grafts from the third-party donor on chimeras that had already accepted such skin grafts led to a prompt rejection of both third-party grafts but not of donor type skin grafts, suggesting that the immune capacity to reject third-party skin grafts has already been attained in such chimeras. It is therefore suggested that the prolonged tolerance to third-party skin grafts may be associated with the origin of the bone marrow--derived cells in the skin graft. PMID- 8456485 TI - Detection of single cells secreting IFN-gamma, IL-6, and IL-10 in irreversibly rejected human kidney allografts, and their modulation by IL-2 and IL-4. AB - The frequency of isolated low-density graft-infiltrating cells (GIC) secreting IFN-gamma, IL-6, and IL-10 was studied in 8 cases of irreversible rejection of human renal allografts, using ELISA and SPOT-forming cells (ELISPOT) assays. The GIC were mostly CD8+ T cells, although CD4+ T cells, B cells, and macrophages could also be detected. On the average, in 10(6) cells, 189 secreted IFN-gamma, 747 IL-10, and 17114 IL-6. Culture of GIC in the presence of IL-2 resulted in an increase in the frequency of IFN-gamma-producing cells (IFN-gamma-PC), in a dose dependent manner, with an optimal 6.5-fold increase at 50 U/ml. In contrast, 25 U/ml IL-4 decreased the frequency of spontaneous and IL-2-induced IFN-gamma-PC by 71.3% and 52.8%, respectively. Furthermore, IL-4 reduced the frequency of IL-6-PC (56.8%). By this new approach to graft rejection, it becomes easier to determine cytokine profiles within an allograft and to study their modulation by different agents. It could be a useful model of study for the development of new treatment. PMID- 8456486 TI - Cellular mechanisms underlying differential rejection of sequential heart and lung allografts in rats. AB - As the simultaneous transplantation of two or more organs into a single recipient has become increasingly common, asynchronous allograft rejection has become an important clinical problem. To investigate the cellular and molecular mechanisms underlying differential organ rejection, we developed a rat model in which heart and lung allografts were transplanted sequentially. Heterotopic heart allografts transplanted into DA recipients from PVG donors survived indefinitely if the recipients were given a short course of rabbit antirat thymocyte globulin or cyclosporine at the time of transplantation. In contrast, orthotopic left lungs transplanted under the same conditions were rejected in ATG-treated recipients and accepted in most CsA-treated recipients. These animals were then given a second organ allograft from the same strain or a third party to assess whether they exhibited donor specific tolerance and whether the acceptance or rejection of the first allograft would influence the survival of the second transplant. Animals tolerized to a heart allograft with ATG rejected an orthotopic lung transplant from the same strain as the original allograft, whereas recipients treated with CsA at the time of their heart transplant accepted a subsequent lung graft. Surprisingly, animals treated with either ATG or CsA that had rejected a lung allograft accepted a subsequent heart transplant. Using limiting dilution analysis and adoptive transfer studies, we found that some recipients had developed suppressor cells while others demonstrated anergy. We conclude that major histocompatibility complex antigens as well as other antigens are involved in the differential rejection of heart and lung allografts. PMID- 8456487 TI - The effect of purified class II major histocompatibility complex antigen on the survival of vascularized organ allografts in the rat. PMID- 8456488 TI - A significant increase of islet yield by early injection of collagenase into the pancreatic duct of young donors. PMID- 8456489 TI - Assessment of pancreas graft viability preserved by a two-layer (University of Wisconsin solution/perfluorochemical) method after significant warm ischemia. PMID- 8456491 TI - The beneficial effects of isradipine on renal hemodynamics in cyclosporine treated renal transplant recipients. PMID- 8456490 TI - A single-center experience with shared six-antigen-matched cadaver renal transplants. PMID- 8456492 TI - Angiosarcoma in an arteriovenous fistula following successful renal transplantation--a case report. PMID- 8456493 TI - Prolonged neurological disability following OKT3 therapy for acute renal transplant rejection. PMID- 8456494 TI - The cardiac transplant recipient with disseminated intravascular coagulation--an unusual kidney donor. PMID- 8456495 TI - Hypophosphatemia induced by acyclovir. PMID- 8456496 TI - What role for 15-deoxyspergualin in enhancing engraftment of unrelated, histoincompatible canine marrow grafts and preventing graft-versus-host disease? PMID- 8456497 TI - Single-lung versus liver transplantation for the treatment of portopulmonary hypertension--a comparison of two patients. PMID- 8456498 TI - Regulating genes by packaging domains: bits of heterochromatin in euchromatin? PMID- 8456499 TI - Delineation of individual chromosomes of Saccharomyces cerevisiae by two-colour in situ hybridization. PMID- 8456500 TI - Optimization of PCR performance. PMID- 8456501 TI - A scientific basis for cost-benefit analysis of genetics services. AB - Economic appraisal of genetics services is important, but, in this sensitive area, analyses limited to financial aspects understandably cause public concern. Evaluation of these services must take account of their aim of helping everyone with a genetic disadvantage to live and reproduce as normally as possible, and must apply equally to patients and to couples at risk of having affected children. Here we propose that the classical concept of genetic fitness can be useful in evaluating genetics services, because it is measurable, and truly represents their underlying aim. PMID- 8456502 TI - Chromosome distribution, molecular motors and the claret protein. AB - Recently, proteins have been identified that are required for proper distribution of chromosomes in meiosis and mitosis. Unexpectedly, several of these are microtubule motor proteins. This finding has prompted further investigation into the basis of meiotic and mitotic chromosome movement. The claret protein, or ncd, is one of the new motor proteins that may perform several functions in meiosis and early mitosis in Drosophila. PMID- 8456503 TI - Control of photosystem genes in Rhodobacter capsulatus. AB - Two environmental factors, oxygen and high light intensity, are known to repress synthesis of the Rhodobacter capsulatus photosystem. One level of regulation is the control of light harvesting and reaction centre gene expression at the point of transcription initiation. This has recently been shown to involve transcriptional activators which exhibit sequence similarity to members of the 'two-component' class of prokaryotic regulators. An additional level of regulation involves the formation of 'superoperons' that transcriptionally link pigment biosynthesis operons with operons that code for the light harvesting and reaction centre structural genes. A final level of regulation involves the selective degradation of reaction centre mRNA transcripts which influence the stoichiometric synthesis of the light harvesting and reaction centre complexes. PMID- 8456504 TI - High-frequency phenotypic switching in Candida albicans. AB - Most strains of Candida albicans are capable of switching spontaneously and at high frequencies between a number of phenotypes distinguished by colony morphology. Unlike switching in many other microbial pathogens, switching in C. albicans is pleiotropic, affecting several morphological and physiological parameters. Recently, the first phase-specific genes were identified and shown to be regulated at the level of gene transcription. PMID- 8456505 TI - [Liver transplantations in Denmark: should we be glad or sorry?]. PMID- 8456506 TI - [Liver transplantation in Denmark. First-year experiences]. AB - During the first 12 months of the Danish Liver Transplantation program, which began in October 1990, 21 transplantations were performed in 11 women, six men and three children. One patient required a retransplant. Fourteen operations were performed electively and six patients were transplanted for acute and subacute fulminant liver failure and coma, two patients had reduced size livers because of large donor liver. There were no peroperative deaths. One of the elective patients died after three weeks from multiorgan failure and sepsis. Two of the emergency patients died after 20 and 22 days. One from graft dysfunction due to stenosis of the celiac trunk and the other of exudative pericarditis. One patient died from chronic rejection and CMV-infection after seven months. Complications were relatively few and acute rejection occurred in 40% of the patients. Fifteen patients are discharged with normal liver function and 11 of these were back at work, school or previous functions in the home. It is concluded that these results are comparable to the best results from other centres but that 21 transplants in 12 months must be a minimum activity. PMID- 8456507 TI - [Fulminant hepatic failure]. AB - Fulminant hepatic failure is a rare disorder with a high lethality. It is characterized by the development of acute hepatic symptoms and encephalopathy, in the absence of underlying chronic liver disease. The main causes are viruses, adverse drug effects and toxins. The major causes of death in patients with fulminant hepatic failure are cerebral edema, infections, gastrointestinal hemorrhage and renal failure, or a combination of these. Treatment of fulminant hepatic failure with a variety of medical therapies has hitherto been found to have little overall influence on outcome. With high volume plasmapheresis the clinical condition of the patients improves, and if there is no sign of spontaneous regeneration, emergency liver transplantation is the only solution. PMID- 8456508 TI - [Plasmapheresis as life-saving treatment in acute hepatic failure]. AB - Emergency liver transplantation is the treatment of choice in acute liver failure without signs of spontaneous regeneration. However, many patients rapidly contract irreversible neurological complications before transplantation can be performed. We used high-volume plasmapheresis to increase the time span to obtain a donor liver. Four patients with acute liver failure of unknown cause and a galactose elimination capacity indicative of a virtually extinct liver function were assigned maximum priority for liver transplantation. Plasmapheresis were performed daily until transplantation. Each time 8-10 liters of patient plasma were replaced with an equal volume of fresh donor plasma. There were no major complications. None of the patients developed irreversible neurological complications for 48-144 h at which time liver transplantation was performed. High volume plasmapheresis increases the time to obtain a donor liver for emergency liver transplantation and optimizes the condition for the surgical procedure. PMID- 8456509 TI - [Partial orthotopic liver transplantation]. AB - From October 1990 to May 1992, nine of 38 patients with liver transplants (24%) had partial orthotopic liver transplantation on account of lack of size-matching donor livers. The preliminary results have presented very few problems; there was no per- or postoperative mortality and no surgical complications. Four patients had episodes of acute rejection which responded to anti-rejection therapy, and two patients were treated for CMV infection. All patients are discharged with normal liver function 4-9 weeks after transplantation (median 5 weeks). The method seems to be safe and can be used in centers with limited activity, where there is a problem of having the correct liver at the correct time. PMID- 8456510 TI - [Liver disease in erythropoietic protoporphyria]. AB - In erythropoietic protoporphyria, the genetically determined decreased activity of the enzyme ferrochelatase causes accumulation of the photoreactive molecule protoporphyrin in various tissues. Dermatological symptoms are dominant, but in some patients the excess protoporphyrin affects hepato-biliary structures, and a spectrum of changes, which ranges from ultrastructural bile canalicular damage to cirrhosis, can be observed. Most clinical reports have described severe cases with a rapid deterioration and a fatal outcome. We present a case with spontaneous recovery from hepatic decompensation on two occasions with three years interval. The first incidence might have been provoked by hormonal substitution therapy. PMID- 8456511 TI - [Treatment of hip fractures in a department of general surgery and a department of orthopedic surgery. A comparison]. AB - All patients treated for fractures of the hip in 1989 in a department of general surgery and a department of orthopedics were included in this study. Data regarding demographics, length of hospitalization, rehabilitation, postoperative complications, types of fractures and modes of operation were retrospectively registered and compared. Mean length of hospitalization was significantly longer and the incidence of postoperative complications was significantly higher in the department of general surgery when compared to the specialized department of orthopedics especially with regard to wound infections and the formation of bedsores. We tentatively propose reasons for these differences. PMID- 8456512 TI - [Computer tomography compared to tomography in suspected femoral neck fractures]. PMID- 8456513 TI - [Psychopharmacological treatment of elderly patients with dementia. Recommendations and guidelines]. AB - Behavioral-disturbed elderly patients with dementia are often treated with psychotropic drugs, frequently by doctors who only have sporadic contact with such cases. Knowledge concerning psychotic symptoms and behavioural disturbances in dementia has increased over the past years, as to a certain extent has the number of investigations of psychopharmacological therapy in demented patients. Based on results of controlled drug trials and empiric consensus among psychogeriatricians, recommendations and guidelines regarding indications for drug therapy and type of psychotropic drug suitable for the treatment of psychiatric problems in dementia are given. PMID- 8456514 TI - [Inappropriate psychopharmacological treatment of the elderly. A 1-year study]. AB - The psychogeriatric department in the county of Arhus is in a unique position to collect cases of old people treated with psychotropics in various inappropriate ways in hospital wards or by general practitioners. In 1991 the department was in contact with 768 elderly people mostly on an outpatient basis among whom 40 patients exhibited accumulated errors of psychopharmacologic treatment. The treatment episodes were analysed. The patients were very old (mean 80.8 years) with severe somatic morbidity. A majority were demented or delirious. 75% were living in nursing homes. The treatment episodes exhibited polypharmacy and large doses of neuroleptics (mean 0.7 DDD/day) or benzodiazepines (mean 1.41 DDD/day). Psychotropics not suitable for elderly patients were used in 34 patients. Indications for treatment were mostly unspecified behavioural disturbances, sometimes reflecting inappropriate social support. The majority of patients had side effects, sometimes rendering the patient more acceptable to staff and other residents. PMID- 8456515 TI - [Smoking habits and risk of coronary heart disease, especially risk associated with low daily tobacco consumption]. AB - The purpose of this study was to estimate the risk of acute myocardial infarction related to smoking habits, especially the risk among smokers with a daily tobacco consumption of five grams or less. The study is based on data from the 1914 population examined by the Glostrup Population Studies at the age of 50 and 60 in 1964 and 1974. Information concerning deaths and cases of hospitalisation has been obtained from national registers up to 1985. Blood pressure, lipids, body mass index and physical activity were used as confounders. It was not possible to make a definite conclusion for the group smoking five grams or less daily as a class, since both the size of the group and the number of myocardial infarctions within it were small. When tobacco consumption was used as a quantitative variable the risk of myocardial infarction was found to increase with increasing amount but the relation was found not to be non-linear. The best description of the tobacco-related risk of myocardial infarction was a logarithmically relation to daily tobacco consumption. PMID- 8456516 TI - [Cardiac events after myocardial infarction treated with streptokinase. The prognostic value of symptom-limited ECG on day 7]. AB - One hundred and forty-seven consecutive patients admitted with suspected acute myocardial infarction (AMI) were treated with streptokinase. On day 7 after AMI 107 patients performed a symptom-limited exercise test (bicycle ergometer). Thirty-four of the tested patients developed at least one cardiac event (reinfarction, cardiac death, decided myocardial revascularization) during follow up (30 months). Exercise induced ST-depression was more frequent among patients with cardiac events than among those without cardiac events (chi 2-test, p < 0.05). With multiple logistic regression analysis (BMPD) the following variables were found to have independent prognostic value for the development of new cardiac events: low maximal heart-rate during the exercise test, long duration of acute symptoms before streptokinase treatment and male sex. Exercise-induced ST depression had no prognostic value in the BMPD-analysis. Exercise testing can be carried out with safety and supplies prognostic information concerning future cardiac events in patients with streptokinase-treated AMI. PMID- 8456517 TI - [Metachronous liver metastases treated with repeated liver resections and chemotherapy]. AB - A patient with a radically resected rectosigmoid cancer underwent two liver resections for metachronous metastases. When a third hepatic recurrence was diagnosed, further surgery was considered technically impossible, and the patient was given chemotherapy with 5-fluorouracil and folinic acid. He went into complete remission, and seven and a half years after the resection for colorectal cancer no metastases in the liver can be shown by ultrasonography or CT scan. The patient has normal CEA, and is at work. PMID- 8456518 TI - [Plasma endothelin immunoreactivity in liver disease and the hepatorenal syndrome]. PMID- 8456519 TI - [Is treatment of increased total cholesterol level indicated?]. PMID- 8456520 TI - [Side effects of water-soluble roentgen contrast media]. PMID- 8456521 TI - [Eye protection during phototherapy]. PMID- 8456522 TI - [Ciclopiroxolamine. A pyridone derivative for local use in fungal infections of the skin and nails]. PMID- 8456523 TI - Correlations between acoustic and texture parameters from RF and B-mode liver echograms. AB - Radio frequency (RF) echograms were acquired from human subjects without liver pathology (n = 126), who were in the range of 20 to 84 years of age. After appropriate correction for the equipment settings and performance characteristics, acoustospectrographic parameters were estimated. The data were corrected for the frequency-dependent attenuation and then software demodulated. Image texture parameters were calculated based on the assumption of a particular tissue model, and purely statistical parameters were also estimated. The data thus obtained from each subject were corrected for the age trend that was assessed in an earlier publication by the authors. A total of 18 parameters was considered and the correlations were analyzed. It is concluded that nine parameters could be identified which did not strongly correlate with each other. This conclusion is supported by analysis of correlation data from patients. In a companion paper, a discriminant analysis is reported, based on the selected parameters (nine) and applied to the differentiation between normals and various classes of diffuse liver disease. PMID- 8456524 TI - Detection of diffuse liver disease by quantitative echography: dependence on a Priori choice of parameters. AB - Quantitative acoustic parameters and image texture parameters were used in a linear discriminant analysis. This analysis was applied to detect retrospectively the classes of diffuse liver disease against a population of normal livers. Three different sets of parameters were employed. The first set was selected by the authors, and the other two were taken from the literature. The area under the Receiver Operating Characteristic (ROC) (or percentage correct classification) obtained with the first set ranged from 88% to 97%, depending on the disease class. It is concluded that the first-order statistical parameters of the image texture (diffuse scattering model) together with the slope of the attenuation coefficient are the most important parameters. As an alternative to the texture parameters, the backscattering parameters (second set of parameters) also yielded a comparably high score. The texture analysis involving structural scattering (third set of parameters) produced a lower percentage of correct classification. The overall conclusion is that the methods devised might be used for prospective diagnosis. PMID- 8456525 TI - Methodology for three-dimensional reconstruction of the left ventricle from transesophageal echocardiograms. AB - A technique is presented for three-dimensional (3-D) reconstruction of the left ventricular endocardial surface from multiplanar transesophageal echocardiograms, using both commercial software and investigator written Fortran programs for Intel 80286 and 80386 microcomputers. The approach provides quantitative global and regional cardiac performance measures and allows viewing the endocardial surface, at end-diastole and end-systole, from chosen perspectives. Anatomical landmarks are incorporated to aid in orientation. For regional calculation, the surface is divided into equal angular elements with each conceptually connected to the left-ventricular end-diastole centroid, forming a pyramidal volume element. This angular division automatically normalizes for heart size. The fractional change of these elements over the cardiac cycle provides a regional ejection fraction measure which is color-coded on the reconstructed endocardial surface. Composite perspective views, regional ejection fraction histograms and calculations of global end-diastolic, end-systolic, and stroke volumes, are all performed by the method. PMID- 8456526 TI - Intrarenal Doppler findings of upstream renal artery stenosis: a preliminary report. AB - To diagnose 60% or greater diameter-reducing stenosis of the renal artery (RAS), color Doppler imaging (CDI) and angiography were performed on 44 hypertensive and 16 normotensive cases. In this prospective, double-blind study we evaluated the related intrarenal waveform changes. In both the right and left kidneys of normotensive cases, at the level of interlobar arteries, the results indicated a symmetric finding in peak systolic/end diastolic velocities (S/D), pulsatility index (PI) and resistive index (RI) ratios. The results in the stenotic kidneys among the hypertensive group indicated that index values were significantly lower in the stenotic kidneys than those of the contralateral kidneys, the kidneys of control and nonstenotic hypertensive cases. To quantify this observation we suggest "perfusion indexes," which require more studies on a greater number of hypertensive cases. It was concluded that measuring the index values of intrarenal arterial waveforms is easier and more accessible in diagnosing RAS than obtaining those of the main renal artery. PMID- 8456527 TI - Effect of perfusion and blood content on ultrasonic backscattering of liver tissue. AB - The purpose of this study was to determine the effect of blood flow perfusion and red cell content on ultrasonic scattering by liver tissue. Data acquisition for ultrasonic tissue characterization (UTC) employing analysis of the backscattered echoes from the power spectrum was obtained from the same region of pig liver tissue under four conditions: 1) normal perfusion in situ, 2) ischemia in situ in the living pig, 3) ischemia in situ immediately postmortem, and 4) immediately after excision of the liver. Discriminant function analysis was used to evaluate differences in the two basic parameters from the normalized power spectrum: slope and intercept. Normal perfused liver had significantly higher intercept values and lower slope values than liver under the other three conditions. Excised liver showed the lowest intercept and highest slope values (p < 0.01). These experiments indicate that differences in perfusion produce significant differences in ultrasonic scattering by liver tissue (ischemia caused a 3 dB drop in intercept amplitude). Normal or ischemic in vivo and in vitro liver tissue is associated with different patterns of ultrasonic scattering, and scattering data under these various circumstances are not equivalent. PMID- 8456528 TI - Comparison of various agents in contrast enhancement of color Doppler flow images: an in vitro study. AB - The commercially manufactured contrast agents, Echovist and Albunex, were compared with sonicated conventional agents, indocyanine green, 29% renografin 60, 0.9% normal saline and 25% mannitol in their ability to enhance color Doppler flow signals. In a pneumatically regulated pulsatile flow system, a glycerine, saline (0.9%) and sand (5 microns particle size) solution was imaged using a 2.5 MHz phased-array transducer. Four different flow velocities (0.40, 0.35, 0.30 and 0.25 m/s) as measured by color Doppler guided pulse Doppler were utilized. All color Doppler settings were kept constant throughout the study. Utilizing a power injector, four different volumes (1.0, 1.5, 2.0 and 2.5 mL) of each contrast agent were injected into the flow medium at various transducer angles (20, 30, 40 and 60 degrees) and various distances from the transducer (3.38, 5.5, 6.76 cm). For Echovist and Albunex, several concentrations varying from 2% to 100% were used. Keeping instrument settings constant, color flow areas obtained before and after each contrast injection were planimeterized and the percent increase in the color flow area computed and compared. At full (100%) concentration, 20 degrees transducer angle and a flow velocity of 0.40 m/s, the maximum increase in the color flow area was 568%, 251%, 180%, 110%, 71%, and 38% for Echovist, Albunex, sonicated indocyanine green, renografin, normal saline and mannitol, respectively. However, a significant reduction in the degree of color flow enhancement was observed, with decreases in the concentration of these agents, and increases in the Doppler beam incident angle or distance from the transducer. Increasing the flow velocity of the medium into which contrast was injected did not produce significant changes in the contrast enhancement effect for all agents except Echovist. Increasing the injection volume significantly increased the color flow area for sonicated agents but not for Echovist or Albunex. This preliminary in vitro study shows that the commercially manufactured contrast agents, Echovist and Albunex, are much superior to sonicated conventional contrast agents in the enhancement of color Doppler flow signals. Of the sonicated agents, indocyanine green had the best enhancement capability. PMID- 8456529 TI - Thickness of tissues intervening between the transducer and fetus and models for fetal exposure calculations in transvaginal sonography. AB - In transvaginal scanning the tissues intervening between the fetus and transducer are relatively thin. The average thickness in the first trimester is 25 mm and reduces to 15 mm by the third trimester; the minimum thicknesses are 14 and 8 mm, respectively. Two models are proposed for calculating exposure in transvaginal scanning. The models are considered in terms of the overlying tissues and the target tissues. A fixed path, constant attenuation of 0.3 dB/MHz describes the properties of the overlying tissues throughout pregnancy. In the model used in first-trimester scanning, the target tissues of the embryo/fetus are considered to have properties similar to those of soft tissues, and they attenuate the energy at the same rate as the overlying tissues. In the model used in second- and third-trimester scanning, the bony structures of the fetus are the target tissues. These reflect 30% of the incident energy and attenuate all of the transmitted energy at their surface. PMID- 8456530 TI - Histological changes in rat liver tumours treated with high-intensity focused ultrasound. AB - This paper reports the histological changes found in rat liver tumours treated with high-intensity focused ultrasound. HSN fibrosarcoma, implanted subcapsularly in the livers of CBH rats, were treated using an array of ultrasound exposures. At predetermined times following treatment, the rats were sacrificed and tissue specimens were examined histologically. Evident tissue damage was confined to regions that had been given high ultrasound exposures. Within these regions ("lesions") there was no evidence of intact cells whereas in the sharply demarcated surrounding tissue there was no evidence of cell damage. Where individual ultrasound lesions had been placed in sufficiently close proximity, there was correspondingly continuous and complete cell destruction. There is suggestive evidence that tissue damage may arise through two different mechanisms: direct, primarily thermal, damage and indirect damage resulting from compromised blood supply. Under the same exposure conditions, normal liver cells appear to lose their morphological structure more readily than do tumour cells. PMID- 8456531 TI - The response of normal and malignant cells to ultrasound in vitro. AB - The effect of ultrasonic irradiation on the viability of normal and tumor cell cultures derived from human and mouse origins was investigated. The cells were irradiated with a frequency of 2 MHz and intensity of 0.33 W/cm2, up to 4 min and immediately tested for cell viability using four different parameters: vital staining for the determination of the rate of cell growth; [3H]-thymidine and [3H]-leucine incorporation as an indication of the rate of DNA and protein synthesis respectively; and cloning efficiency as a measurement of the cell ability to multiply. Two human normal cell lines used in our studies, FS11 foreskin fibroblasts and Wish cells, were relatively resistant to ultrasonic irradiation effect although the growth rate of the latter was somewhat affected, particularly after 2 or 4 min of irradiation. However, cells derived from either malignant melanoma or breast carcinoma were highly sensitive to irradiation as demonstrated by a reduction of 96% and 65%, respectively, in cloning efficiency even after irradiation for 1 min. A third tumor cell line derived from lung carcinoma was more resistant. Two normal clones derived from NIH/3T3 mouse fibroblasts were used. These clones revealed some degree of sensitivity, particularly after 4 min of irradiation. However, their murine-sarcoma-virus transformed counterparts were found to be even more sensitive at identical times of ultrasonic irradiation, although the differences are not as striking as demonstrated with cells from human origin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8456532 TI - A comparison of hemolytic and sonochemical activity of ultrasonic cavitation in a rotating tube. AB - Biological effects of in vitro ultrasonic exposure may result from mechanical and from sonochemical mechanisms related to ultrasonic cavitation. Mechanical cell lysis by 1.61 MHz ultrasonic cavitation was assessed in a rotating tube exposure system by hemolysis measurements. Free radical generation was assessed by the terephthalic acid dosimeter, calibrated by gamma-ray dosage. Sonochemical production was assessed by measuring residual hydrogen peroxide using the sensitive isoluminol method. Exposure conditions were similar for all tests, except longer durations were needed for the free radical and hydrogen peroxide tests. The sonochemical mechanisms were relatively more important for increasing intensity, and increasing temperature. Increasing rotation speed or bubbling with argon before exposure enhanced all cavitation activity. Stopping the rotation reduced all cavitation activity. Burst-mode ultrasound (10.5 microseconds bursts, 1:1 or 1:3 duty cycle) reduced cavitation activity, but gave relatively greater sonochemical activity under some conditions. These results indicate that the mechanical and sonochemical mechanisms can be separately favored to some extent by varying exposure conditions. The observed trends should be helpful for selecting exposure conditions favorable for studying bioeffects of the sonochemical mechanism. PMID- 8456533 TI - The feasibility of using MRI to monitor and guide noninvasive ultrasound surgery. PMID- 8456534 TI - Short-term culture of exfoliated cells from the urine of patients with bladder tumors. AB - This report concerns the short-term culture of urothelial cells from the urine sediment of over 100 patients with bladder tumors. Primary cell outgrowth was obtained in approximately 60% of the cultures initiated. Culture outcome was not related to tumor grade, patient age, or volume of the urine sample. Around 85% of the proliferating cultures were successfully transferred into multi-compartment chamber/slides. These results suggest that the culture system may be a useful tool for the study of urothelial cells using patient material obtained by non invasive means. PMID- 8456535 TI - Characterization of insulin-like growth factor I binding sites in human bladder cancer cell lines. AB - The role of insulin-like growth factor I (IGF-I) in the growth and development of bladder cancer cells was investigated using cultured human cell lines representing differentiated (RT-4, 5637) or undifferentiated (T-24, J-82, TCC SUP) transitional cell carcinoma (TCC). In the presence of 2% serum, IGF-I significantly stimulated the growth of all cell lines. The proliferation of T-24, 5637, and RT-4 cells was more sensitive to IGF-I than that of J-82 and TCC-SUP cells. [125I]IGF-I binding to 5637 and J-82 cells was significantly higher than that to T-24 and TCC-SUP cells (P < 0.001). RT-4 cells possessed the lowest binding capacity among the cell lines tested. Scatchard analysis of [125I]IGF-I binding to four of the five cell lines indicated a single binding site for IGF-I, with apparent dissociation constants (Kd) of 1.27, 1.18, 1.34, and 1.39 nmol/l for TCC-SUP, J-82, 5637, and T-24, respectively. Therefore, the difference observed in [125I]IGF-I binding among the bladder cancer cell lines was attributed to the difference of IGF-I binding sites and not to a change in receptor binding affinity. Cross-linking studies supported the suggestion that [125I]IGF-I was bound to a receptor on these cells. The results indicate that cultured human bladder cancer cells contain functional IGF-I receptors. A differentiated cell line, RT-4, possesses significantly fewer IGF-I receptors than other cell lines. This suggests that the overexpression of IGF-I receptor may reflect the malignant potential of bladder cancer cells. PMID- 8456536 TI - Keyhole limpet hemocyanin immunotherapy of murine bladder cancer. AB - The current treatment of choice for superficial bladder cancer, bacillus Calmette Guerin, has significant adverse side effects. We have compared two alternative immunotherapies--crude keyhole limpet hemocyanin (KLH) and Immucothel, a KLH modified for clinical use (Biosyn)--in an intralesional mouse model of bladder cancer (MBT2). Crude KLH required either immunization before tumor transplant or frequent intralesional therapy after transplantation to be effective. In addition, Immucothel required pre-immunization to be effective, and increasing the frequency and dosage of post-transplant immunization was not effective without pre-immunization. Preliminary investigations into the KLH-induced anti tumor mechanism(s) suggest that natural killer cell activity may be involved. Both crude KLH and Immucothel appear to be effective immunotherapies of use in the treatment of transitional cell carcinoma. PMID- 8456537 TI - Urethral function after cystectomy: a canine in vivo experiment. AB - To study the function of the pelvic floor and the isolated urethra after removal of the bladder, 5 male and 5 female mongrel dogs were used in an acute in vivo experiment. Urethral pressure changes secondary to unilateral stimulation of the pelvic and pudendal nerves were recorded. After baseline data of the intact system were documented, the following procedures were carried out: separation of the urethra from the bladder neck (prostate), nerve-sparing cystectomy (cystoprostatectomy), and cold-knife incision through the entire length of the proximal urethra. Pressure recordings were repeated after each step of surgery. Pudendal nerve stimulation resulted in rapid and large pressure rises in the distal urethra (reaction typical of striated muscle). This response remained unchanged after all three surgical steps. Pelvic nerve stimulation provoked pressure rises within the urethra of a pattern typical of smooth muscle. The findings persisted after separation of the urethra from the bladder neck (prostate) and after cystectomy, but were not observed after urethrotomy. Contractions secondary to pudendal nerve stimulation were inhibited by curare, which did not affect the reaction to pelvic nerve stimulation. Our experiments demonstrate that in the dog the continuity of bladder and urethra is not required for the function of urethral closure mechanisms. The contractile potency of the urethral smooth muscles remains intact after nerve-sparing cystectomy. We believe that problems with the baseline continence of surrogate bladders should mainly be ascribed to a lack of surgical caution in preserving the autonomic nerves of cystectomy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8456538 TI - A method for isolating smooth muscle cells from pig urinary bladder with low concentrations of collagenase and papain: the relation between calcium concentration and isolated cell length. AB - The present study describes a method for isolating single smooth muscle cells from pig urinary bladder using a continuous resuspension device. Low concentrations of collagenase and papain were sufficient to obtain a high yield of viable smooth muscle cells, which remained viable for about 3-4 h as tested with fluorescein diacetate. Addition of fetal calf serum increased the lifespan of the isolated cells and the percentage of contractile smooth muscle cells, but caused spontaneous shortening of the cells. The length and volume of the isolated smooth muscle cells depended on the calcium concentration used in the isolation buffer solution. The isolated muscle cells were apparently relaxed if a calcium concentration less than 1.0 mmol/l was used in the isolation medium. In higher calcium concentrations the isolated cells were significantly shorter, probably as a result of a contraction caused by mechanical stimulation of the cells during the isolation procedure. PMID- 8456539 TI - Oxalate status in stone-formers. Two distinct hyperoxaluric entities. AB - A retrospective analysis of oxalate status in 115 stone-forming individuals revealed hyperoxaluria in 30%. These individuals could be divided into two distinct groups according to urinary oxalate excretion patterns and plasma oxalate levels. The cause of hyperoxaluria in one group may be explained on the basis of increased absorption of dietary oxalate and decreased renal clearance. Hyperoxaluria in the other group appears to be a consequence solely of enhanced endogenous production of oxalate. These two entities can be distinguished from one another in the context of a routine metabolic evaluation of calcium stone disease when urine and plasma oxalate measurements are included. PMID- 8456541 TI - Histopathologic effects of extracorporeal shock wave lithotripsy on rabbit kidney. AB - Despite the widespread clinical use of the lithotriptor, the margin of safety for the kidney during shock wave application is substantially unknown. Although a series of pilot studies have been performed in laboratory animals, long-term follow-up is mandatory to establish the effect of extracorporeal shock wave lithotripsy (ESWL) and subsequent dose-dependent changes on the kidneys. An experimental study was performed in 45 rabbits; to define and compare the early and late complications of ESWL in the kidneys. The rabbits were divided into three groups of 15 animals each that received 1000, 1500 or 3000 shock waves respectively at 15-20 kV. The rabbits in each group were killed and necropsy performed within 24 h for the first 5 animals, 1 week for the second 5 animals and 2 months post-ESWL for the last 5 animals. Dose-dependent moderate damage (subcapsular hemorrhage, interstitial hemorrhage, capsular tension and perirenal hemorrhage) were noted in all kidneys at 24 h after treatment. Evidence of permanent changes (some fibrosis, tubular and glomerular damage, chronic inflammatory alterations) was noted in long-term follow up. Complete necrosis of the treated kidney was not encountered in this study. PMID- 8456542 TI - Changes in seminal fluid zinc during experimental prostatitis. AB - Patients with prostatitis have been found to have decreased prostatic fluid zinc (PF Zn). It is unclear whether changes of prostatitis are due to an inherent lack of Zn in some patients or whether the changes, including reduced PF Zn, are due to the infectious process itself. Six nonhuman primates were infected with 1 x 10(5) E. coli JR340, a clinical isolate known to cause prostatitis in the monkey. After infection, seminal fluid for culture and zinc assay was obtained by electroejaculation. Zinc was measured by colorimetric analysis. Blood counts, quantitative renal scans and urine cultures were also monitored. The animals were followed for 4 weeks and then sacrificed. The histopathology showed resolving prostatitis and fibrosis. Zinc levels dropped with acute infection, and variably recovered as the infection cleared. Controls showed slight variability with respect to PF Zn. It appears that PF Zn decreases as a result of the infectious process. PMID- 8456540 TI - Isolation and purification of a new glycoprotein from human urine inhibiting calcium oxalate crystallization. AB - A calcium oxalate crystal growth inhibitor was isolated from human urine using DEAE-Sephacel gel followed by Sephacryl S-300 chromatography and FPLC column. The isolated inhibitor was a uronic-acid-rich protein (UAP). It was found to be a glycoprotein with a molecular weight of 35,000 Da as determined by SDS polyacrylamide gel electrophoresis. Inhibitory activity was demonstrated using a calcium oxalate crystallization system. In addition UAP, nephrocalcin (NC) or nephrocalcin-like (NC-like) activity was an effective inhibitor in this system. However, the inhibitory activity of UAP appeared to be higher than that of NC or NC-like activity. This finding suggests that NC or NC-like activity is not only urinary protein with strong inhibitory activity. UAP and probably other proteins also play a role in the control of urinary crystal growth. PMID- 8456543 TI - Penile erections induced by vasoactive intestinal peptide and sodium nitroprusside. AB - The use of vasoactive intestinal peptide (VIP), sodium nitroprusside (SNP), and the reference combination of papaverine, prostaglandin E1, and phentolamine was studied in 22 adult cats. The maximal erectile response (intracavernous pressure, penile length, and rigidity) was produced by intracavernous injection of a combination of 1.65 mg papaverine, 0.5 micrograms PGE1, and 25 micrograms phentolamine. This combination was considered as "control" in order to compare the effect of other agents. VIP and SNP increased the intracavernous pressure and caused erection in a dose-dependent manner with a maximal response obtained with 5 micrograms VIP or 10 micrograms SNP. The duration of peak erection and the total duration of drug effect were significantly shorter with VIP and SNP than with the reference combination (P < 0.01). Epinephrine (30 micrograms) reversed the effects of SNP and significantly shortened the duration of peak action and total effect (P < 0.05). This study supports the use of an in vivo feline model for the evaluation of vasoactive agents and demonstrates that the intracavernous injection of either VIP or SNP can induce penile erection in the adult cat. PMID- 8456544 TI - Oil on Shetland. PMID- 8456545 TI - Immunisation of cattle with a recombinant vaccinia vector expressing the haemagglutinin gene of rinderpest virus. AB - The efficacy of a recombinant rinderpest vaccine, constructed by inserting the rinderpest virus haemagglutinin gene into attenuated vaccinia virus, LC16mO strain, was tested in cattle. After subcutaneous inoculation of 10(8) plaque forming units (pfu) of the recombinant vaccine, neither palpable skin lesions nor increases in body temperature were observed, indicating the absence of detectable clinical reactions. All the vaccinated cattle were completely protected from challenge with the Saudi 1/81 strain of virulent rinderpest virus. Contact control cattle housed in the same pen with the vaccinated animals did not develop antibodies to rinderpest or vaccinia viruses, and developed typical clinical signs of rinderpest after challenge with virulent rinderpest virus, indicating that there was no contact transmission of the recombinant virus. The 50 per cent protective doses of the vaccine, estimated by the mortality and morbidity rates respectively. were 10(4) and 10(5) pfu. To observe the effect of pre-existing immunity to vaccinia virus on the efficacy of the vaccine, cattle inoculated with the Lister strain of vaccinia virus three weeks earlier, were vaccinated with the recombinant virus. These animals developed antibodies to rinderpest virus and were protected from challenge with virulent rinderpest virus, showing that the vaccine was effective in animals already immune to vaccinia virus. The effectiveness and safety of the vaccine demonstrated in this study suggest that it has potential as a new vaccine against rinderpest. PMID- 8456546 TI - Yellow discoloration in veal calves: the role of hepatic copper. AB - Liver samples from four groups of calves were analysed chemically and histologically for copper and iron levels. Milk replacer-fed 'yellow' calves were compared with milk replacer-fed 'white' calves, concentrate and silage-fed 'pink' calves and concentrate and silage-fed young 'red' fattening bulls. In the milk replacer-fed calves high copper and low iron levels were measured in the liver, whereas in the concentrate and silage fed pink calves and fattening bulls lower copper and higher iron levels were found. The yellow calves appeared to be icteric and had chronic hepatitis. Their hepatic histopathology was characterised by fibrosis, cirrhosis, fatty change, increased amounts of stainable copper, necrobiosis and prominent cholestasis; some animals had intranuclear inclusion bodies in the hepatocytes. They had similar or lower hepatic copper levels than the white calves and varying iron levels, indicating that copper toxicity was not the primary cause of the hepatic damage. PMID- 8456547 TI - Nematode egg output and plasma concentration of ivermectin after its administration to red deer (Cervus elaphus elaphus). AB - Blood and faecal samples were analysed in a study to evaluate the use of ivermectin in red deer hinds (Cervus elaphus elaphus). It was demonstrated that ivermectin, when used at 400 micrograms/kg bodyweight, proved to be more efficient than 200 micrograms/kg bodyweight although positive worm egg counts together with the isolation of lungworm (Dictyocaulus species) larvae were recorded from hinds having received the anthelmintic at the higher dose. PMID- 8456548 TI - Incidence of the rob.t (1;29) centric fusion translocation in British White cattle in Britain. PMID- 8456549 TI - ELISA in the identification of cattle herds at risk from dictyocaulosis. PMID- 8456551 TI - Bovine embryo transfer certification. PMID- 8456550 TI - Freedom from filth. PMID- 8456552 TI - Absence of antibodies to avian pneumovirus in Canadian poultry. PMID- 8456553 TI - Equine motor neuron disease. PMID- 8456554 TI - A flow-cytometric approach to quantitative estimation of platelet surface immunoglobulin G. AB - Flow cytometry (FC) was used to estimate platelet-surface IgG (PSIgG) by quantifying the fluorescence of platelets incubated with a fluorescein isothiocyanate (FITC)-labelled polyclonal goat anti-human IgG antibody or FITC labelled non-immune goat IgG. Results were expressed as relative fluorescence intensity (RFI) defined as the ratio of specific fluorescence (mean fluorescence of platelets incubated with the FITC anti-IgG) over non-specific fluorescence (mean fluorescence of platelets incubated with FITC non-immune goat IgG). A normal range was formed by analysing platelets from 71 healthy subjects. Platelets from 16 patients with a firm clinical diagnosis of immune-mediated thrombocytopenia had a mean RFI significantly higher (p < 0.001) than the controls, whereas platelets from 9 patients thought to have non-immune thrombocytopenia had an RFI not significantly different from the normal controls. From a prospectively studied group of 62 patients with no clinically obvious cause for their thrombocytopenia or impaired platelet function 35.5% had raised PSIgG. In order to express the results as number of IgG molecules per platelet, reference curves were created by using FC to measure PSIgG of platelets coated with known amounts of a chimeric IgG (human IgG with murine hypervariable region) monoclonal antibody to the glycoprotein IIb-IIIa complex. Normal platelets had an average 1,463 (SD = 927) molecules of PSIgG. In patients with immune-mediated thrombocytopenia the levels ranged from 690 to 32,328 (mean 11,535) molecules per platelet. Flow-cytometric PSIgG estimation was sensitive, fast and easy to perform and therefore suitable for both research and clinical service purposes. PMID- 8456555 TI - Molecular genetic analysis of the ABO blood group system: 1. Weak subgroups: A3 and B3 alleles. AB - We have determined the nucleotide sequences of the coding region in the last two coding exons of ABO genes (which occupy 91% of the soluble form of A1 transferase) from 7 individuals with weak subgroup phenotypes. Four of the individuals had an A3 phenotype and 3 individuals had a B3 phenotype. We determined the nucleotide sequences based on PCR followed by subcloning and DNA sequencing of the amplified fragments. Two cases of the A3 allele and 1 case of the B3 allele were found to contain a single-base substitution which resulted in an amino acid substitution. However, no other cases of A3 and B3 alleles were found to contain differences in this region. This finding demonstrates for the first time heterogeneity among these weak subgroups at the nucleotide level. PMID- 8456556 TI - Molecular genetic analysis of the ABO blood group system: 2. cis-AB alleles. AB - We have determined the nucleotide sequence of the coding region in the last two coding exons of ABO genes from two cis-AB individuals (genotype cis-AB/O) with no consanguinity. In this region, cis-AB alleles from these 2 individuals were identical to one another while different from the A1 allele by two nucleotide substitutions. Both of these nucleotide substitutions result in amino acid substitutions. The first substitution is identical to the one previously found in the A2 allele. The other substitution is found at the fourth position of the four amino acid substitutions which discriminate A1 and B transferases. PMID- 8456557 TI - Prevalence of hepatitis B and C virus infections among haemodialysis patients in Pune (western India) PMID- 8456558 TI - T-transformed red cells--role of minor cross-match in patients with T antigen activation. PMID- 8456559 TI - Intravenous immunoglobulin therapy of autoimmune and systemic inflammatory diseases. AB - The proven beneficial effect of intravenous immunoglobulins (IVIg) in certain autoimmune disorders has led to the development of clinical trials in other autoimmune and systemic inflammatory diseases. In parallel, experimental studies are being carried out to better understand the mechanisms of action of IVIg. In this review, we discuss the clinical use of IVIg in autoimmune disorder and the possible mechanisms by which IVIg may be effective in the various diseases. A better understanding of the mechanisms of action of IVIg in autoimmune disease will allow optimization of their use as a therapeutic alternative to conventional immunosuppression. PMID- 8456560 TI - Blood donations indeterminate in HIV-1 western blot analysed by IgM immunoblot and polymerase chain reaction. AB - The presence of IgM antibodies to human immunodeficiency virus 1 (HIV-1) was investigated in blood donor sera which were indeterminate in anti-HIV-1 IgG Western blot testing. In 7 of 173 instances out of approximately 1,000,000 blood donation sera with an isolated anti-p24 IgG produced an anti-gp41-45 IgM immunoblot reaction. Applying polymerase chain reaction (PCR) to 29 indeterminate samples out of approximately 125,000 blood donations it was found that 2 of them were IgM-positive and also contained HIV-1-specific DNA sequences. Eleven months later 1 of these 2 donors was retested and found IgM and PCR negative. PMID- 8456561 TI - Posttransfusional hemolysis in recipients of glucose-6-phosphate dehydrogenase deficient erythrocytes. AB - To test the hypothesis that transfusion of blood donated by individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency may result in a hemolytic reaction, we conducted a prospective longitudinal study in which 10 patients transfused with 1 unit of G6PD-deficient and 1 unit of normal red blood cells (RBC) were compared with 10 patients transfused with 2 units of age-matched normal RBC. We found that 24 h after transfusion serum bilirubin (mumol/l) in the recipients of G6PD-deficient RBC was significantly higher than in the recipients of normal RBC (36 +/- 14 vs. 18 +/- 5, respectively, p > 0.004). A parallel increase was found in the serum lactate dehydrogenase (LDH; IU/l) between the two groups (378 +/- 151 vs. 264 +/- 56, p < 0.001). The difference in serum bilirubin (26 +/- 10 vs. 15 +/- 5, p < 0.03) was still noted 48 h after transfusion, with only a marginal difference (p < 0.08) in LDH. We conclude that an immediate posttransfusional hemolytic reaction can occur in recipients of G6PD-deficient RBC and therefore suggest that the differential diagnosis of posttransfusional hemolysis, particularly in populations where G6PD deficiency is prevalent, includes transfusion of erythrocytes from G6PD-deficient donors. PMID- 8456562 TI - Import control of irradiated foods by the thermoluminescence method. AB - A thermoluminescence (TL) method was applied for the import control of irradiated foods. The method is based on the determination of the TL of mineral contaminants in foods. Detection of irradiation was incorporated in official Finnish control procedures in spring 1990. For foodstuffs with a reduced microbe content and in which no fumigant residues are found, possible irradiation is investigated by the TL method. The minerals are separated from the foods in different ways: picking is used for spices; water rinsing for herbs, spices, berries and mushrooms; high density liquid to separate the organic material from the mineral fraction in seafood; and carbon tetrachloride for foods forming gels with water. To date about 140 food samples have been analysed for control purposes: 50 samples of herbs and spices, 25 samples of berries and mushrooms and 65 samples of seafood. Of these, 14 samples of herbs and spices and 5 samples of seafood were shown to have been irradiated. Differences in TL intensity between irradiated and unirradiated samples were at least 1 and usually 3-4 orders of magnitude. PMID- 8456563 TI - Intake of polychlorinated biphenyls (PCB) from the Finnish diet. AB - Concentrations of seven single PCB indicator congeners were measured in 99 food samples. These concentrations were converted into a total PCB content and used for estimating total PCB intake among Finns. The average intake from food is 15 micrograms/day or 0.25 mu/kg body weight per day, which showed no change during the late 1980s. Approximately half of the intake comes from fish. The composition of the PCB mixture varies a lot in different sample types, which emphasizes the importance of single compound determination. PMID- 8456564 TI - [Determination of the folic acid content of vegetables and fruits using high performance liquid chromatography (HPLC)]. AB - The folic acid content of vegetables (including potatoes) and fruits was determined by means of high-performance liquid chromatography (HPLC). Free folate (monoglutamate forms) and total folate (monoglutamate+polyglutamate forms) are differentiated. Vegetables contained 27-187 micrograms/100 g and fruits 10-80 micrograms/100 g total folate. The free folate portion ranged from 6.3% to 96.8% (mean 35%) in vegetables and from 11.6% to 89.0% (mean 56%) in fruits. In addition, the results of the quantification of the main folate derivatives tetrahydrofolic acid (THF), 5-methyltetrahydrofolic acid (5-CH3-THF) and 5 formyltetrahydrofolic acid (5-CHO-THF) are presented. The mean values were 70% 5 CH3-THF, 20% 5-CHO-THF and 10% THF. Their total, resulting from the addition of pteroylglutamate equivalences, is comparable with the results of microbiological methods reported in the tables of nutritive values. PMID- 8456565 TI - Incidence of infections in pigs bred for slaughter revealed by elevated serum levels of interferon and development of antibodies to Mycoplasma hyopneumoniae and Actinobacillus pleuropneumoniae. AB - Pigs in three specialized fattening herds were studied with respect to some immune functions, viral infections revealed by presence of interferon-alpha in serum as well as bacterial infections indicated by antibodies to Mycoplasma hyopneumoniae and Actinobacillus pleuropneumoniae. Pigs from different breeders had signs of varying but low incidence of such infections. After transport to the fattening herds, viral infections were activated and spread during the first month, and a maximum of 19% of the pigs had signs of ongoing infections at one week. At this time, blood leukocytes prepared from the pigs had diminished ability to produce interferon-alpha in vitro. Except during the first month, serological evidence of Mycoplasma hyopneumoniae infections became gradually more frequent, and 91% of the pigs were seropositive at slaughter. Early, but not late, infections appeared to inhibit growth of the pigs as indicated by time for slaughter, but only late infections may be registered as pneumonia at slaughter. The prevalence of pigs with serological evidence of Actinobacillus pleuropneumoniae infections increased late in the fattening period, but such infections had no demonstrable impact on the time for slaughter. PMID- 8456566 TI - Diagnostic value of phage typing, antibiogram typing, and plasmid profiling of Staphylococcus hyicus from piglets with exudative epidermitis. AB - A total of 989 isolates of S. hyicus were recovered from the skin of 103 piglets (9.6 isolates per piglet) with exudative epidermitis (EE), and phage typed. Phage patterns of 806 typable isolates (81%) could be divided into 44 distinct phage types. From 1 to 6 different phage types were found on individual piglets, with an average of 1.9 phage type per piglet. Antibiogram patterns of 384 isolates from 40 randomly selected piglets with EE showed a mean of 2.3 different antibiograms per investigated piglet, ranging from 1 to 6 antibiograms per piglet. Plasmid profiles of 248 S. hyicus isolates from 25 randomly selected piglets showed an average of 2.8 different plasmid profiles per piglet. Seven EE outbreaks in pig herds vaccinated with autogenous vaccine were investigated. In all these herds, strains recovered from the present outbreak differed by two or more type markers to the strains from the previous outbreak used for production of the autogenous vaccine. This finding suggest, that lack of protection might be due to the presence of other virulent types in the investigated herd than those used for production of autogenous vaccine. PMID- 8456567 TI - An evaluation of an intradermal test for the diagnosis of bovine herpesvirus type 1 (BHV-1) infection in cattle. AB - An intradermal (ID) test (a delayed-type hypersensitivity test) was used for the diagnosis of BHV-1 infection in cattle. A threshold value for the test positive results was established based on the analysis of the agreement between the results of ID test and those of virus neutralization (VN24) assay. Linear regression analysis revealed no correlation between the intensity of the skin reaction (expressed as an increase in skin-fold thickness) and the VN24 antibody titre. The sensitivity and specificity of the ID test compared to VN24 one, were 86.6% and 98.3% respectively. Of the 487 cattle with an age of over 6 months, 25 (5.1%) reacted discordantly by ID and VN24 tests, i.e. 19 seropositive animals expressed little or no skin reaction, whereas 6 seronegative individuals were positive by ID. Neither of the calves, with passively acquired antibodies in contrast to experimentally infected ones, showed distinctive skin reaction. PMID- 8456568 TI - Preliminary evaluation of a simple method for detection of bovine tuberculosis: the glutaraldehyde test. AB - The glutaraldehyde test (GT) is performed by mixing whole blood with a 1.25% glutaraldehyde solution. Gelification time is shorter in tuberculous cattle. This test was performed in blood samples obtained from: (a) 48 cattle with bacteriologically confirmed tuberculous lesions; (b) 61 animals with no evidence of tuberculosis at the time of slaughterhouse inspection, 14 of which had hydatid cysts; (c) 260 tuberculin-negative apparently healthy animals, and (d) 21 cattle, also tuberculin-negative but serologically positive for brucellosis. Sensitivity for detecting tuberculosis was 85.4% (41 of 48 animals). The test was negative in 298 out of 307 healthy animals (97.1% specificity). This specificity decreased when the test was applied in animals with evidence of diseases other than tuberculosis. This simple, rapid and inexpensive method could play a complementary role to the tuberculin test for detecting tuberculous cattle, especially in endemic areas with scarce resources and facilities. PMID- 8456569 TI - [The amine-forming ability of Aeromonas spp]. AB - Motile Aeromonas (A.) species are considered international more and more as potential food poisoning organisms. Their ability to produce biogenic amines, products of metabolism, which in case can cause a disease, was only searched insufficiently till now. 50 strains of the species A.hydrophila, A.sobria, A.caviae and the non-motile species A.salmonicida were included in the tests for amine producing potency. Qualitative investigations to the formation of histamine, tryptamine, and tyramine were ensued by the help of thin layer chromatography. Quantitative investigations were only done in respect of the production of tyramine, which had been proved qualitatively in several strains, while histamine and tryptamine were not produced. Concentrations of tyramine with foodhygienic relevance were found out partially. PMID- 8456570 TI - Viruses of Chelonia. AB - Viruses occurring in turtles and tortoises are hetergeneous but according to ecologic characteristics and pathogenic properties they can be divided in two major groups: 1. Arboviruses (toga-, flavi-, rhabdo- and bunyaviruses) transmitted by arthropods cause severe diseases in homoiothermic vertebrates. The viruses are of great epidemiological interest in human and veterinary medicine. Chelonia and other reptiles infected by bites of vectors e.g. Aedes, Anopheles, Culex develop cyclic viremia without injury. The ectothermic animals maintain inapparent arbovirus infections during hibernation and they play role as reservoirs for these viruses. 2. Viruses of Chelonia origin (papova-, herpes-, irido- and paramyxoviruses) associated with diseases of infected turtles and tortoises have been described frequently during the last 20 years. Several viruses or virus-like particles could be demonstrated in affected reptiles mainly by electron microscopy. Especially herpesviruses seem to attack Chelonia and epizootics due to infections with these viruses were reported in several reptiles in collections. However, the etiological role of the agents detected is not well documented yet. PMID- 8456571 TI - Experimental systemic bovine zygomycosis with reference to pathology and secretion of antigen into urine. AB - ELISA and immunoblotting were applied for the characterization of somatic antigens from Absidia corymbifera. Immunoblotting revealed major antigenic bands at 11 to 81 kDa. The ELISA showed some crossreactivity towards somatic antigens from other fungi. However, the crossreactivity was especially observed with somatic antigens from other fungi of the zygomycetes. The ELISA and immunoblotting assays were applied to urine samples from two groups of 3 calves each systemically infected with A. corymbifera and Aspergillus fumigatus, respectively. The immunoreactivity of the urine samples was similar by the two assays. Somatic antigens were demonstrated in the urine of all three calves infected with A.corymbifera, whereas only one of the calves with systemic aspergillosis was antigen positive. The level of antigen in the positive urine samples varied from 50 to 210 ng/ml. PMID- 8456572 TI - Essential data needs of nurses in all practice settings. PMID- 8456573 TI - Pain corner. Analgesics: from the oral route to an alternate route. PMID- 8456574 TI - The Adult Critical Care Nursing (ACCN) post-basic distance education program: flexibility in learning. PMID- 8456575 TI - Nursing research challenges: a personal view. PMID- 8456576 TI - Nurses and the political process. PMID- 8456577 TI - Holistic nursing. Part one--A definition. PMID- 8456578 TI - Breastfeeding tidbits. PMID- 8456579 TI - M.S.--a winning option. PMID- 8456580 TI - Dr. Sara Fry. Interview by Eve Henderson. PMID- 8456581 TI - Radioimmunolocalization and quantification of liver metastases and subcutaneous tumours from a human colonic cancer xenografted in the nude rat. AB - The purpose of the present investigation was to improve the conditions for radioimmunolocalization (RIL) and radioimmunotherapy (RIT) of colonic cancer, using experimental models of the human disease. A tumour model was created in the nude rat by intraportal injection of a mechanically disintegrated cell preparation of the human colonic cancer cell-line LS 174 T, producing liver metastases in a dose-dependent fashion. A conventional subcutaneous (s.c.) tumour model was also employed, where LS 174 T cells were inoculated into a hindleg of nude rats. A technique was developed for quantification of liver metastases by means of contrast-enhanced CT, using an iodinated lipid emulsion. CT quantification proved feasible post mortem and also in vivo, the latter enabling repeated therapy evaluation in the same animal. Post mortem quantification of hepatic metastases was also accomplished by computer-based area calculation (CBAC) on serial liver sections. The three evaluation procedures were in agreement for quantification of intermediate and extensive hepatic metastatic growth, but not for livers with small and few metastases. A similar CT evaluation technique, may also be possible for human application. Several pharmacokinetic aspects of RIL were evaluated, using the 125I-labelled anti-carcinoembryonic antigen (CEA) monoclonal antibody (MAb) preparations I-38S1, AEC 38 and II-16. MAb AEC 38 was produced by additional purification of I-38S1 by anion exchange chromatography. Most MAb I-38S1, AEC 38 and II-16 accumulated in the s.c. xenografts during the first 24 h, the maximum being reached on days 2-4, depending on the MAb preparation used. The patterns of uptake and clearance of AEC 38, I-38S1 and II-16, found in gamma camera registrations, were in agreement with those of external detector measurements. Additional purification of I-38S1 by anion exchange chromatography improved the in vivo MAb uptake in s.c. xenografts, but its immunoreactivity in vitro was impaired by this procedure. The uptake of I-38S1 in hepatic metastases was not size dependent and was higher than in s.c. xenografts, irrespective of the mode of MAb injection (i.p. or i.v.). Uptake of I-38S1 in s.c. xenografts was independent on injection mode. By contrast, in liver metastases there was a marked tendency toward a higher uptake of I-38S1 following i.p. vis-a-vis i.v. antibody administration, although not statistically significant, possibly due to an apparent variability between animals and between different liver metastases in the same rat. This variability was not evident for s.c. xenografts.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8456582 TI - A survey of some commercially available kits and reagents which include bioluminescence or chemiluminescence for their operation: including immunoassays, hybridization, labels, probes, blots and ATP-based rapid microbiology. Products from more than forty companies. AB - This survey was compiled between January and November 1992 from public domain information requested by the author from companies specializing in these products. It includes individual sections giving the name and address of each company together with brief details of their (a) kits used for assay of certain analytes in the routine laboratory and (b) reagents used mainly as research tools. This survey is a companion to a previous survey about 90 commercially available luminometers. PMID- 8456583 TI - Early loading-related changes in the activity of glucose 6-phosphate dehydrogenase and alkaline phosphatase in osteocytes and periosteal osteoblasts in rat fibulae in vivo. AB - The tibiae and fibulae of 14-week-old rats were subjected to a single 5 minutes period of cyclic longitudinal loading at 1 Hz. The activity of the enzymes glucose 6-phosphate dehydrogenase (G6PD) and alkaline phosphatase (ALP) in osteocytes and periosteal osteoblasts was measured immediately and 24 h after loading. In osteocytes G6PD activity was increased immediately after loading but returned to control values 24 h later. There was no detectable ALP activity in these cells regardless of loading history. In periosteal osteoblasts G6PD activity was raised immediately after loading and remained higher than controls 24 h later. ALP activity in periosteal cells was unaffected immediately after loading but 24 h later was substantially increased. These findings are consistent with osteocytes and periosteal cells both being immediately responsive to periods of intermittent loading in their adjacent matrices. In both cell types an early feature of this response is an increase in G6PD activity. In osteocytes this response is short-lived, suggesting that it is an early biochemical change associated with strain perception that does not progress to matrix synthesis. The increase in G6PD activity with unaffected ALP levels in periosteal cells immediately after loading is consistent with a similar response. In these cells the increase in G6PD accompanied by increased ALP levels 24 h after loading suggests that the loading-related response progresses to new bone formation. PMID- 8456584 TI - Attachment to extracellular matrix molecules by cells differing in the expression of osteoblastic traits. AB - Two sets of clonal cell populations differing in the expression of osteoblastic traits, the rat osteosarcoma cell lines ROS 17/2.8 and ROS 25/1 and the immortalized fetal rat calvarial cell lines RCT-1 and RCT-3, were compared for their ability to attach to a series of extracellular matrix (ECM) constituents in vitro. Both osteoblastic (ROS 17/2.8, RCT-3) and nonosteoblastic (ROS 25/1, RCT 1) cell lines attached in a time- and concentration-dependent manner to plates coated with fibronectin (FN), osteopontin (OP), type I collagen (Col I), type IV collagen (Col IV), and laminin (LN) but only weakly to osteocalcin (OC) and thrombospondin (TSP). In both systems, the osteoblastic and nonosteoblastic clones attached identically to FN. Both ROS 17/2.8 and ROS 25/1 attached to similar molar amounts of substrate with the same preference order: FN > LN > Col I > or = Col IV. Maximal ROS 17/2.8 attachment to OP was > or = Col I but required approximately 2.5 times more substrate. ROS 25/1 attached less effectively than ROS 17/2.8 to most non-FN substrates. RCT-3 cells attached similarly to ROS 17/2.8 except that the preference order for Col I and LN was reversed and attachment to OP was lower than for ROS 17/2.8 RCT-1 cells attached best to Col I rather than FN, and equaled or surpassed RCT-3 in attachment to other non-FN substrates. Thus in these experimental systems, cells expressing an osteoblast-like phenotype exhibited generally similar ECM attachment properties. Their nonosteoblastic counterparts recognized the same spectrum of ECM constituents but differed from the osteoblastic cells and from each other in the effectiveness of their attachment to substrates other than FN. PMID- 8456585 TI - Differential expression of alkaline phosphatase in clones of human osteoblast like cells. AB - We established cultures of cells growing out from adult bone chips and maintained them through 12 passages in culture. The cultures showed osteoblastic phenotype accompanied by synthesis of collagen type I, osteonectin, alkaline phosphatase, and osteocalcin. We report the characterization of 21 clones obtained from three different individual primary cultures. We studied the expression of osteonectin, alkaline phosphatase, collagen, and osteocalcin in the clones. Metabolic labeling showed production of type I collagen and of osteonectin in all clones studied. In two-thirds of the clones and in mass cultures alkaline phosphatase was not detected at passage 2, but it was detected in increasing amounts at later passages in culture. The clones attained different but detectable levels of expression of this marker by passage 8. The different levels in the expression of alkaline phosphatase in positive clones may be because they were derived from cells at different stages of osteoblastic maturation or due to small changes in microenvironment. The alkaline phosphatase-positive clones were tested for osteocalcin, and they showed measurable expression only at passage 10. A third of the clones obtained were negative for alkaline phosphatase during 12 passages in culture. The obtainment of clones unable to produce alkaline phosphatase may be due to loss of differentiating potential under the in vitro culture conditions. The growth rate and potential of all clones studied were similar through 12 passages in culture, regardless of their potential for expression of alkaline phosphatase. PMID- 8456586 TI - Measurement of intrinsic bone quality in vivo by reflection ultrasound: correction of impaired quality with slow-release sodium fluoride and calcium citrate. AB - The intrinsic (material) quality of cancellous and cortical bone was evaluated in vivo from the measurement of reflection ultrasound velocities in the ulna. In cancellous bone, the reflection ultrasound velocity was inversely correlated with age in normal women (r = -0.48, p = 0.001), with a significantly lower mean value in 32 normal postmenopausal women than in 14 premenopausal women (3124 versus 3341 m/s, p < 0.0001). In 32 untreated osteoporotic women the cancellous bone velocity was lower than in normal postmenopausal subjects (2906 versus 3124 m/s, p = 0.0001). Following treatment with slow-release sodium fluoride plus calcium citrate (mean 2.4 years in 33 osteoporotic patients with no fracture during treatment), the cancellous bone velocity was significantly higher than in untreated osteoporotic women (3082 versus 2906 m/s, p = 0.0002) and was not significantly different from that in normal postmenopausal women. The cortical bone velocity displayed similar trends, but the changes did not attain statistical significance. The measurements were repeated approximately 9 months later in 9 untreated and in 20 treated patients; in 5 additional patients, the measurements were made both before and after 9 months of treatment with slow release sodium fluoride and calcium citrate. The cancellous bone velocity increased significantly (p = 0.046) in these patients, from 3008 m/s before treatment to 3112 m/s after the first 9 months of treatment. The velocity rose significantly from 3037 to 3167 m/s (p = 0.017) in patients treated for a short time (12-30 months at first measurement), but it did not change in untreated patients or those treated for more than 30 months. Thus, the material quality of cancellous bone decreases with normal aging and is reduced further with the osteoporotic process. This impaired quality may be corrected by treatment with slow-release sodium fluoride plus calcium citrate. PMID- 8456587 TI - Rapid and sensitive method of quantitation of bone gla protein mRNA using competitive polymerase chain reaction. AB - A method for sensitive quantitation of bone gla protein (BGP, osteocalcin) mRNA has been developed using competitive polymerase chain reaction after reverse transcription (competitive RT-PCR). The complementary DNA (cDNA) were transcribed from sample RNA was co-amplified in a PCR with a known amount of mutant BGP cDNA (competitor) using the identical oligonucleotide primers. The mutant cDNA with its unique restriction site allowed quantitation of sample and mutant PCR products after densitometric analysis of ethidium bromide-stained agarose gels. A linear relationship between initial sample BGP amount and the ratio of BGP to mutant BGP band intensity was obtained and used to make a standard curve to determine the initial BGP mRNA of unknown samples. These standard curves were made with known amounts of recombinant BGP cDNA. The competitive RT-PCR for BGP allows measurement of twofold differences in 1 and 2 micrograms total RNA and requires at least 10 times less sample RNA than usual Northern blotting. Moreover, heteroduplexes with one BGP strand and one mutant BGP strand formed as a result of high PCR cycles were quantifiable. This provided the advantages of rapid quantitation from ethidium bromide-stained gels without blotting, hybridization, or autoradiography. Multiple samples could be assayed for greater confidence in the results. The sensitivity, accuracy, and ease of the assay will facilitate analysis of BGP mRNA from a small amount of sample. The assay has been used to confirm the BGP mRNA changes with hormonal treatment in cultured cells and the age-related changes in whole tibia in vivo. PMID- 8456588 TI - Bone disease in burn patients. AB - Burn patients are at risk for bone disease due to aluminum (Al) exposure from use of antacids and albumin, partial immobilization, and increased production of endogenous glucocorticoids. Moreover, severely burned children are growth impaired up to 3 years after the burn. To determine the extent of bone disease, we studied nine men and three women, ages 18-41 years, with greater than 50% body surface area burn. Seven patients underwent iliac crest bone biopsy following double tetracycline labeling, one additional patient expired after a single label, and three others had postmortem specimens obtained for quantitative Al only. Serial serum and urine samples were obtained weekly until biopsy or death. All biopsied patients had reduced bone formation and osteoid area, surface, and width, with mineral apposition rate, osteoblast surface, and osteoclast number with normal eroded surfaces compared to age- and sex-matched normal ambulatory volunteers. Burn patients also had reduced bone formation, mineral apposition rate, osteoid area, and surface compared to age-matched volunteers at short-term bed rest. Serum levels of osteocalcin were low. Most patients had mild hypercalcemia but only a third had hypercalciuria. All patients had elevated Al in blood or urine; urine Al correlated inversely with serum osteocalcin. In 60% significant bone Al was detectable by stain or quantitation. Our data are compatible with burn patients having markedly reduced bone turnover. Al loading, partial immobilization, endogenous corticosteroids, and cytokine production may be among the etiologic factors. PMID- 8456589 TI - Effect of ovariectomy on bone response to in vivo external loading. AB - This study was undertaken to find whether the bone response to increased external loading (EL) of the tibia in rats is affected by estrogen depletion. Female Sprague-Dawley rats 6 months were randomly assigned to four groups of 10 each: sham ovariectomy without loading (Shm-XL), ovariectomy without loading (OVX-XL), sham ovariectomy with external loading (Shm-EL), and ovariectomy with external loading (OVX-EL). In vivo external loading by a four-point bending device was initiated 4 weeks after surgery. The right lower leg of each EL rat was loaded at 31.4 +/- 0.2 N for 36 cycles at 2 Hz every other day for 21 days (11 loading days). Mean in vivo induced strain was 1305 microstrain (mu epsilon) for Shm-EL rats and 1280 mu epsilon for OVX-EL rats. With external loading of the tibia, periosteal bone formation rose equally in Shm and OVX rats. Woven bone was present around the tibia or fibula in 60% of the loaded rats and none of the control rats. No loading response occurred either at the endocortical surface or in the cancellous bone of the proximal tibial metaphysis. After OVX, cancellous bone area in the proximal metaphysis declined and formation surface rose compared to Shm rats. Although periosteal and endocortical bone formation rose after OVX, no cortical bone loss occurred. We conclude that ovariectomy and attendant loss of endogenous estrogen do not change the cortical bone response to an external load of about 1300 mu epsilon in rats. However, these results may not predict the cortical bone response to loading in animals with Haversian remodeling that display estrogen-related loss of cortical bone. PMID- 8456590 TI - Mechanism of action of estrogen on cancellous bone balance in tibiae of ovariectomized growing rats: inhibition of indices of formation and resorption. AB - Ovariectomy results in cancellous osteopenia in rat long bones, a condition that is prevented by treatment with estrogens. The purpose of these studies was to clarify the effects of estrogen on cancellous bone turnover using dynamic bone histomorphometry. Treatment of ovariectomized rats with diethylstilbestrol (DES) reduced the mineral apposition rate, double-label perimeter, osteoblast number, and osteoclast number, suggesting that the hormone had inhibitory effects on bone formation as well as bone resorption. However, we could not estimate the bone formation rate because of rapid resorption of tetracycline-labeled bone in the ovariectomized rat. The magnitude of loss was documented by a time course study: 58% of the tetracycline initially incorporated into the secondary spongiosa of the tibial metaphysis was resorbed after 11 days and 89% was resorbed after 22 days. Similarly, cancellous bone area was decreased by 67% after 11 days and by 88% after 22 days. Administration of either DES or tamoxifen (TAM) dramatically reduced resorption of tetracycline as well as the decrease in cancellous bone area. These results demonstrate that (1) estrogen prevents osteopenia in ovariectomized (OVX) rats, in part by inhibiting bone turnover, (2) TAM is an estrogen agonist on bone resorption, and (3) resorption of tetracycline-labeled bone leads to serious underestimation of the bone formation rate in OVX rats. PMID- 8456591 TI - Pattern of gene expression following rat tibial marrow ablation. AB - Following injury to bone marrow there is a phase of osteogenesis in which bone trabeculae replace the initial blood clot and fill the marrow cavity. The newly formed bone is subsequently fully resorbed by osteoclasts and normal bone marrow is restored. In this study we correlated the morphologic events with the pattern of gene expression that defines this sequence. Following marrow ablation, the trabecular bone volume in the affected section of the marrow cavity increased from control to 27% at day 6, declined to 18% at day 8, and eventually returned to control levels at day 14. Osteoblast number increased up to day 6 and declined substantially by day 8, but the number of osteoclasts peaked between days 8 and 10. Histologic analysis of alkaline phosphatase (AP) and tartrate-resistant acid phosphatase (TRAP) activity correlated with the observed cellular changes. Northern blot analysis of the levels of AP, osteocalcin (OC), and osteopontin (OP) mRNA shows a specific pattern of regulated gene expression, with AP mRNA maximal at day 6, OC mRNA very low until days 6-8, and OP mRNA expressed at very high levels throughout. In addition, procollagen alpha 1(I) and alpha 1(III) mRNAs show a regulated pattern of expression, with procollagen alpha 1(I) maximally expressed between days 4 and 10 and procollagen alpha 1(III) expressed at lower levels between days 4 and 6. The mRNA encoding insulin-like growth factor I (IGF-I) was found to be highly expressed between days 5 and 12; however, transforming growth factor beta 1 (TGF-beta 1) and TGF-beta 3 mRNA were only weakly expressed between days 4 and 10. These data demonstrate a temporal pattern of gene expression consistent with the observed morphologic profile, identify changes in growth factor mRNA that may be related to this repair process, and suggest that this is a suitable model for studying in vivo a synchronized sequence of bone formation and resorption at a well-defined anatomic site. PMID- 8456592 TI - An unusual case of epileptic transient aphemia. Clinical and neuropsychological findings. AB - A patient with unusually prolonged epileptic aphemic attacks following a surgical lesion in the left frontal lobe is described. Clinical, electroencephalographic and neuropsychological findings are reported. True aphemia is relatively rare and the described case affords the opportunity of emphasizing that a relatively rare disorder of language as aphemia might also occur with true epileptic attacks. PMID- 8456593 TI - Probable cerebellar abnormality on 123I-IMP SPECT scans in epileptic patients with long-term high-dose phenytoin therapy. Based on observation of multiple cases. AB - Quantitative assessment of regional cerebral blood flow (rCBF) in the bilateral cerebral and cerebellar cortices was performed in 13 epileptic patients receiving long-term high-dose phenytoin (PHT) therapy, using single photon emission computed tomography (SPECT) with N-isopropyl-(iodine 123) p-iodoamphetamine. In 4 of the 13 patients, both the cerebellar to frontal rCBF ratio and cerebellar to cerebral rCBF ratio showed low values as compared with those in 22 normal subjects matched for sex and age, probably reflecting abnormal relative cerebellar hypoperfusion. None of the 4 patients showed any abnormal findings on X-ray computed tomography or magnetic resonance brain imaging. The patients with a history of acute PHT intoxication tended to show the abnormal relative cerebellar hypoperfusion. These results suggest the utility of SPECT scans for early detection of cerebellar abnormalities known to be often present in epileptic patients, and imply a risk of long-term high-dose PHT therapy. PMID- 8456594 TI - High-dose methylprednisolone infusions in relapsing and in chronic progressive multiple sclerosis patients. One year follow-up. AB - Sixty Multiple Sclerosis patients hospitalized either in relapse (28) or in chronic progressive (32) phase of the disease were treated with high-dose methylprednisolone infusions (1 g/daily for 6 days). Clinical examinations, scored by Kurtzke's functional systems (FSs) and expanded disability status scale (EDSS), were performed before treatment, immediately after, and thereafter at 1,3,6 and 12 month intervals. In relapsing cases, 22 patients (78.6%) improved and EDSS mean value decreased by 1.39 points after the treatment; 8 patients had a new bout within one year. In chronic progressive cases, 18 patients (56.2%) improved and EDSS mean value decreased by 0.56 points after the treatment; 13 patients showed a new worsening throughout the follow-up period. The treatment proved to be safe and effective both in relapsing and in chronic progressive patients, determining rapid clinical improvement in most of the cases, and a slowing down of progression in some chronic patients. PMID- 8456595 TI - Treatment of cognitive impairment secondary to degenerative dementia. Effectiveness of oxiracetam therapy. AB - The effectiveness of Oxiracetam (1600 mg/day) versus placebo was assessed in a group of 96 out-patients suffering from cognitive disorders secondary to primary degenerative dementia. The study lasted twelve months and was performed in two stage, a) double-blind (26 weeks) and b) open study (26 weeks). The assessment of the results obtained at two, six and twelve months was carried out following both the methodology based on neuropsychological tests and scales, and the study of the simple reaction time by any of a computerized portable tachystoscope. The patients treated with Oxiracetam showed a statistically significant improvement of simple reaction time and cognitive function detected by the Attention matrix. In the placebo group after twelve months a significant worsening of cognitive and global function was observed in comparison with baseline scores. The patients themselves appeared in favor of Oxiracetam. The drug tolerability proved to be very good for the whole duration of the treatment. The authors believe that Oxiracetam favorably acts on the symptoms of senile cerebral deterioration and can improve the capability of information processing, as suggested by the better performances obtained at the reaction time test and at the Attentional Matrix test. PMID- 8456596 TI - Nasu-Hakola disease. A case accompanied by abnormalities in fatty acid composition of serum total lipids and amino acid analysis. AB - A case of Nasu-Hakola disease (membranous lipodystrophy) was reported. The patient is a 33-year-old man who started to have pathological fractures at the age of 24 years. Then, neurological symptoms such as dementia appeared gradually. A biopsy specimen of the bone showed membranocystic changes of the adipose tissue. T2-weighted magnetic resonance images of the head showed low intensity in bilateral putamens, internal capsules, globi pallidi and caudate nuclei. One of his brothers has the same disease. In both patients, fatty acid composition of serum total lipids showed increased nervonic acid and plasma amino acid analysis showed decreased glutamine. PMID- 8456597 TI - Mood disorders in epilepsy. AB - Depression is a common psychiatric problem associated with epilepsy. Interictal depressive symptoms are more frequent and severe in epileptic patients than in subjects with comparable chronic neurologic diseases or physical handicaps. Epileptic depression was characterized as major or dysthymic: bipolar depression is rarely described. Several Authors are of opinion that interictal depression is more frequent in epileptics with temporal lobe foci and, in particular, with temporal left hemisphere lesions. The pathogenetic significance of depression in epileptics is unclear. Some suggest the hypothesis that depression represents behavioral effects of neurochemical responses to brain injury for asymmetrical hemispheric distribution of neural substrate for mood. We think that depression in epileptic patients does not represent a psychological reaction to a particular cognitive or physical impairment, but it is in some way related to the type of epilepsy. In addition, some antiepileptic drugs may have psychotropic effects: the most positive findings were associated with carbamazepine. PMID- 8456598 TI - Quantitative assessment of regional cerebral blood flow with 123I-IMP in normal adult subjects. AB - Quantitative assessment of regional cerebral blood flow (rCBF) in the bilateral cerebral and cerebellar cortices was performed in 22 normal adult subjects consisting of an early twenties group (5 men and 9 women, 20-22 years) and middle age group (3 men and 5 women, 41-52 years), using single photon emission computed tomography (SPECT) with N-isopropyl-(iodine 123) p-iodoamphetamine. Absolute rCBF values in each region in the 22 subjects ranged from 46 to 102 ml/100 g/min (mean 69.1, standard deviation 13.7 ml/100 g/min). The absolute rCBF values were significantly higher in women than in men, and in the early twenties group than in the middle age group. In addition, based on each absolute rCBF value, the interhemispheric asymmetry, anterior to posterior ratio and cerebellar to frontal ratio in rCBF were calculated. These results may be useful as indexes for detecting organic and functional brain abnormalities in various neuropsychiatric diseases. PMID- 8456599 TI - Parental consent: factors influencing adolescent disclosure regarding abortion. AB - Four hundred thirty-nine females (ages 12-21) seeking abortions were surveyed concerning support networks they utilized during their pregnancy crisis. Fifty one percent of this sample reported confiding in their parents, while 49% reported that they did not confide in their parents. The relationship between perceived dependence, as well as family communication, and the teenagers' decision to seek parental advice regarding their pregnancy crisis was examined. The following variables were used to study the characteristics of these two groups: age, marital status, living arrangements, employment status, maturity, general family communication, and family communication regarding sexuality. The results revealed that the degree of financial and emotional dependence and the quality and nature of family communication were closely related to the teenagers' decision to confide in their parents about the decision to seek an abortion. Implications of the findings include the need for more empirical information before making legislative decisions regarding parental consent. Suggestions for further research include an investigation of the effects of parental responses on teenagers who choose abortion and a comparative examination of the characteristics of families of confiders with those of nonconfiders. PMID- 8456600 TI - Sexual abuse in male children and adolescents: indicators, effects, and treatments. AB - It is believed by many that the sexual abuse of children and adolescents is primarily perpetrated against females. This article presents a review of the literature on the incidence, indicators, effects, and treatment of sexual abuse in males. PMID- 8456601 TI - Case study training for seeing school through adolescents' eyes. AB - The first of two years of training in case study activities, adapted from the program originally developed by Fritz Redl, Daniel A. Prescott, and others at the Universities of Chicago and Maryland in the 1940s, is described. Excerpts from the case study of a 16-year-old female provide examples of activities, such as: (1) identifying recurring patterns of behavior, (2) selecting a pattern of behavior for analysis by the multiple hypotheses method, and (3) summarizing the case study record. The significance of this process is that high school personnel can learn to see what adolescents are up against in and out of school. PMID- 8456602 TI - Under pressure program: using live theatre to investigate adolescents' attitudes and behavior related to drug and alcohol abuse education and prevention. AB - This paper describes the Under Pressure Program, an innovative communication centered approach designed to involve Chicago public junior and senior high school students in considering the problems and prevention of adolescent substance abuse. The centerpiece of the program is a 30-minute live musical play, Captain Clean, which incorporates extensive postperformance dialogue and role play to explore the pressures and feelings of adolescents regarding substance abuse. This unique blend of live entertainment and applied learning techniques enables adolescents to understand the pressures they face and teaches them to make responsible choices, in addition to serving as a vehicle for effective school and community substance abuse intervention. By going beyond the 60-second "just say no" television and radio campaigns, the Under Pressure Program addresses the underlying causes of adolescent substance abuse. Students are engaged in active participation rather than the traditional "teach and preach." The goals of the program are (1) to evaluate the effectiveness of live theatre in preventing and intervening in adolescent substance abuse, and (2) to examine the effectiveness of live theatre, via postperformance dialogue and role playing, in soliciting feedback from adolescents as to their own feelings about substance abuse and using school counselors and other available resources, and to build upon their recommendations for improving substance abuse prevention and intervention programs. The program is targeted at predominantly minority, low income students who have been identified as "high risk." The Under Pressure format consists of four integral parts: faculty/staff community in-service: theatrical performance (Captain Clean); postperformance dialogue and role play; and student, faculty, counselor, and community follow-up. PMID- 8456603 TI - The prevalence of depression in a high school population. AB - This study examined the prevalence of depression in a nonclinical adolescent population (N = 2,698) in a major Canadian city. The Beck Depression Inventory was administered to students in three secondary schools. An analysis of variance revealed significant main effects of age and gender. The percentage of students categorized as experiencing none to mild depression was contrasted with those experiencing moderate to severe depression. Overall, the results showed relatively low rates of severe or moderate depression in this population. The findings are discussed in the context of previous investigations. PMID- 8456604 TI - Variables related to romanticism and self-esteem in pregnant teenagers. AB - In this study, the Dean Romanticism Scale and the Bachman Self-esteem Scale were administered to 121 teenagers between the ages of 12 and 19 in Southern California to investigate their degree of romanticism and self-esteem. The study also explored whether there was any relationship between the dependent variables of romanticism and self-esteem and ten independent variables--age, race, place of residence during pregnancy, age when first sexual intercourse occurred, age when pregnancy occurred, incidence of sexual abuse, incidence of abortion, adoption considerations, whether the subject was currently sexually active, and whether the teenager planned to have a child with the father of the baby. The results indicated that two variables were significantly related to feelings of romanticism--adoption considerations and whether the adolescent planned to have a child with the baby's father. In addition, two variables were significantly related to self-esteem--the incidence of sexual abuse and the incidence of abortion. PMID- 8456605 TI - Parricide rates and criminal street violence in the United States: is there a correlation? . PMID- 8456606 TI - Identity choices in immigrant adolescent females. AB - The adolescent task of ego identity formation is especially complex when it must be carried out in the context of a new country and culture. For immigrant adolescents, whose numbers have grown rapidly in the American school population in the past decade, developing a firm identity involves steering a course between refusing to adapt to American life at all and acculturating too rapidly. Based on semi-structured interviews with five adolescent females, all recent immigrants from Latin America, this paper discusses the active role immigrant adolescents can take in balancing the influences of old and new cultures in the formation of a healthy bicultural identity, and the special problems females face in adapting to a new sex role culture. PMID- 8456607 TI - Perceived actions of parents and attitudes of youth. AB - The present study assessed the self-concepts and evaluations of parents of a sample of high school students. Findings indicated that students' evaluations of parents, but not self-concepts, were significantly correlated with the perceived "loving" actions engaged in by their parents toward one another. These findings are in marked contrast to the results reported by Parish (1988), who surveyed college students, and suggest that more research is needed to determine if these findings are artifacts of the samples surveyed, or are indicative of developmental shifts that occur as individuals move from adolescence to adulthood. PMID- 8456608 TI - Dressing in costume and the use of alcohol, marijuana, and other drugs by college students. AB - This study compared the behavior of college students who wore costumes on Halloween with those who did not. It was designed to examine the degree to which college students disguised their identity at Halloween, whether they masqueraded with a group, and whether these factors were related to alcohol and other drug use behaviors. The sample included 805 females and 448 males from two colleges. They were surveyed over a five-year period. The findings revealed significant associations between dressing in costume and drinking alcohol, and between masquerading with a group and using marijuana and other drugs. No significant associations were found between disguise of identity and the use of alcohol, marijuana, and other drugs. PMID- 8456609 TI - Student responsibility for learning. AB - This paper presents the results of a study of student responsibility for learning, utilizing a student perspective. On the basis of a four-month participant/observation and 52 interviews with sixth and seventh graders at a California middle school, six categories were found that students viewed as being their responsibilities for learning. The categories, from the most to least frequently mentioned, were: (1) Do the Work, (2) Obey the Rules, (3) Pay Attention, (4) Learn or Study, (5) Try or Make an Effort, and (6) Responsibility as Something Given or Taken. It was concluded that the students did not perceive school as a place for learning, saw school as neither challenging nor as allowing them enough control to make the work challenging, and although they said they felt responsible for learning, they were actually just "being held responsible" rather than "being responsible." PMID- 8456610 TI - Indicators of commitment to the church: a longitudinal study of church-affiliated youth. AB - In an attempt to discover the factors that determine which late adolescents drop out of the church and which remain committed to it, a broad sample of Seventh-day Adventist youth was surveyed. These youth were part of a ten-year study which originally involved over 1,500 subjects distributed throughout the United States and Canada. Commitment was found to be related to cognitive, experiential, and activity dimensions of religion. Ethical considerations, a perception of one's importance to the local congregation, and peer influence also played a part in the stepwise regression package, which accounted for half of the variance in commitment scores. PMID- 8456611 TI - The effects of traditional family values on the coming out process of gay male adolescents. AB - The development of a gay or lesbian identity (often referred to as the coming out process) has been widely studied in adults; however, few studies have examined the process in gay adolescents. Even among these studies, little research has investigated the effects of race or family values on the coming out process. A small sample of African-American, Hispanic/Latino, Asian/Eurasian, and Caucasian gay male adolescents participated in this survey study. Coming out was operationalized in three stages: sensitization; awareness with confusion, denial, guilt, and shame; and acceptance. The majority of respondents reported feeling different from other boys as children. The average age of first crush on another boy was 12.7 years; average age for realizing they were gay was 12.5 years. Most respondents reported feeling confused during their first awareness that they were gay. Denial of identity was a coping strategy for about half the sample. Traditional family values played a greater role in predicting coming out experiences than did race. Families were categorized as having high or low traditional values based upon (1) the importance of religion, (2) emphasis on marriage, (3) emphasis on having children, and (4) whether a non-English language was spoken in the home. Families with a strong emphasis on traditional values were perceived as less accepting of homosexuality than were the low traditional families. Those who work with adolescents need to be aware that some will recognize their sexual orientation as gay, lesbian, or bisexual during this time of their lives. These youth need support in the coming out process because they may encounter stigmatization and disapproval not only from the larger society, but also from their families, peers, and sometimes the gay community itself. PMID- 8456612 TI - The religiosity of mothers and their offspring as related to the offspring's sex and sexual orientation. AB - This study sought to determine the nature and extent of the relationship between the religiosity of mothers and their offspring, taking both the sex and the sexual orientation of the offspring into account. Religiosity was measured in terms of both intensity (importance of religion, frequency of church attendance) and denominational preference. Female offspring were found to be more religious than male offspring, and their religiosity tended to more closely resemble that of their mothers than did the religiosity of males. Offspring of both sexes who were not exclusively heterosexual in orientation tended to be less religious and less likely to emulate their mother's religiosity as compared to exclusively heterosexual offspring. PMID- 8456613 TI - Self-concept and academic performance in gifted and academically weak students. AB - This study investigated potential correlates of academic achievement, including self-concept, extracurricular activities, family environment, and gender. Findings indicated that while self-concept and academic achievement were associated for gifted 7th and 8th graders, the two variables were not associated for academically weak students. For this latter group, living with a stepparent was associated with poorer academic performance. PMID- 8456614 TI - The relationship of family structure and family conflict to adjustment in young adult college students. AB - This study examined whether the structural intactness of the family and/or perceived family conflict was related to young adult adjustment as assessed by measures of ego identity status and psychological distress. The physical wholeness model holds that family structure is the major variable affecting adjustment, while the psychological-wholeness model posits family conflict as the critical variable. In the present study, undergraduate college students (N = 285) were classified as belonging to an intact two-parent family or a nonintact family, and as coming from homes characterized by low, medium, or high levels of conflict. A statistically significant relationship between family conflict and adjustment was observed; there was no significant association between family structure and adjustment. Individuals from families perceived as being low or medium in level of conflict reported fewer psychiatric symptoms and demonstrated higher levels of ego identity than did those from families perceived as high in conflict. These findings support the psychological-wholeness model. It is suggested that future research be directed toward developing more refined measures of interpersonal conflict. PMID- 8456615 TI - Predictors of depression in street youth. AB - The extent of depression and other psychiatric problems among adolescent "street" and homeless populations is largely undocumented. Using a sample of 145 adolescent street youth interviewed in Toronto, Canada, this study attempted to extend the knowledge of street youth by examining the association of depression with alcohol and drug use and related problems, social supports, self-esteem, family background, and alcohol and drug use among family members. The results indicated that the best predictors of depression among street youth were self esteem and length of time spent in a hostel. PMID- 8456616 TI - Gender differences in identity development: an examination of longitudinal data. AB - Longitudinal data from 105 junior high school students were analyzed to examine the relationship between gender and identity development over time. Analysis of variance, t tests, and analysis of covariance were employed. Taken collectively, results indicated that patterns of change over time were similar for males and females; as the students aged, they grew in psychosocial maturity regardless of gender. These results are consistent with other work using Eriksonian-based assessment instruments. Gilligan, using ethnographic methodology and a framework at odds with Erikson's, has proposed a very different interpretation of development across gender. Perhaps the two methodologies and the concomitant findings should be considered in a complementary fashion in view of the complex societal forces imposed upon females as they progress in their identity development. PMID- 8456617 TI - Premarital sexuality: a five-year follow-up study of attitudes and behavior by dating stage. AB - This paper presents the results of a survey on premarital sex conducted in 1988. The study focused on what respondents considered proper sexual behavior, what they reported they did, and what they thought others were doing at five stages of dating. Respondents were asked about cohabitation, the effect of AIDS on their premarital attitudes and behavior, and their views regarding the morality of premarital sex. When compared to the results of a similar study conducted in 1983, the data provided some evidence of change in premarital sexual attitudes and behavior. Female respondents in the 1988 sample showed lower levels of sexual intercourse at all five dating stages than did their counterparts in the 1983 study. However, males in the 1988 sample reported higher levels of sexual intercourse for the first four stages of dating than did males in the 1983 survey. In general, both males and females in the 1988 sample reported changing their attitudes and behavior regarding premarital sex in the direction of greater conservatism since hearing about AIDS. Attitudinal change was more widespread than actual behavioral change. PMID- 8456618 TI - Female adolescent contraceptive decision making and risk taking. AB - In a modified replication of an earlier study, cognitive capacity, cognitive egocentrism, experience (sexual/contraceptive behaviors and attitudes), and demographic factors were assessed as predictors of decision making in a contraceptive use paradigm. Additionally, these factors were assessed as predictors of risk-taking behavior--"sensible" use of contraceptives. Sixty sexually active, unmarried females, ages 14-18, served as subjects. Cognitive capacity and cognitive egocentrism variables as well as age, grade, and ethnic status significantly predicted six of the seven decision-making variables. One cognitive capacity variable and one sexual/contraceptive behavior variable significantly predicted "sensible" use of contraceptives. These results are compared to the earlier study and discussed within the context of relevant literature. PMID- 8456619 TI - Personal adjustment during pregnancy and adolescent parenting. AB - This study examined "naturally occurring differences" in personal adjustment (social competence, behavior problems, and problem-solving skills) among representative groups of pregnant and nonpregnant adolescents and pregnant adults. Differences in parenting stress and parenting style were also assessed among a subsample of adolescent and adult mothers. Finally, the relationship between prenatally assessed personal adjustment and parenting was evaluated in the adolescent mother group. The contributions of important demographic characteristics (socioeconomic status and race) to both between- and within-group relationships were examined. Results suggested that pregnant adolescents were less socially competent and less proficient in their problem solving than their nonpregnant peers and that they exhibited more behavioral problems than a pregnant adult comparison group. Adolescent mothers displayed higher levels of parenting stress and were less responsive and sensitive in interactions with their infants than adult mothers. Support for the hypothesized link between prenatally assessed personal adjustment and adolescent parenting stress was found, whereas no relationship between socioeconomic status and race and parenting stress was established. These results suggest that intervention with young mothers identified during pregnancy as having personal problems might forestall parenting problems that arise during early child rearing. PMID- 8456620 TI - Joint destruction in arthritis and osteoarthritis. 19th symposium of the European Society of Osteoarthrology (ESOA), May 24-27, 1992, Noordwijkerhout, The Netherlands. Proceedings. PMID- 8456621 TI - Human and bovine articular cartilage loading measured with a new resistive sensor: effects of protease degradation and osteoarthritis. AB - This report describes the use of a new micro-thin resistive-based sensor to measure dynamic vertical loading of normal and osteoarthritic (OA) human knee cartilage repetitively under conditions of simulated knee joint loading. Articular cartilage discs were cultured in 3 DMEM +/- IL-1, lipopolysacharide (LPS) and trypsin over 7 days. Loading force, force distribution and peak pressure were evaluated. The sensor detected early stiffness and dynamic loading changes due to IL-1, LPS and trypsin treatment, and differences between normal and early OA human cartilages showing decreased cartilage stiffness due to enzyme treatment and osteoarthritis. PMID- 8456622 TI - Possible role of IL-1 in arthritis: effects of prostaglandins in the regulation of IL-1 synthesis and actions. PMID- 8456623 TI - Degradative and repair responses of cartilage to cytokines and growth factors occur via distinct pathways. AB - Cartilage destruction mediated by IL-1 is due to increased matrix lysis and decreased matrix repair. To determine whether the two processes are linked, we studied the influence of growth factors on IL-1 induced neutral protease induction, proteoglycan synthesis inhibition and IL-1 receptor expression. With respect to neutral protease induction, FGF and PDGF potentiated IL-1 activity, TGF-beta inhibited, while EGF, IGF-1 and -2 had no effect. With respect to IL-1 receptor expression, FGF and PDGF induced more IL-1 receptors, TGF-beta inhibited, while IGF-1, and 2 had no effect. Finally, with respect to proteoglycan synthesis, TGF-beta, PDGF and IGF-1 reversed IL-1 induced PG suppression to different extents, while FGF slightly potentiated IL-1 induced suppression of aggrecan synthesis. The results suggest that while IL-1 affects both increased aggrecan loss and decreased synthesis, the pathways leading to the effector functions are not necessarily linked and are likely to be distinct. PMID- 8456624 TI - Does TGF-beta protect articular cartilage in vivo? AB - Repeated intraarticular injections of transforming growth factor beta cause stimulation of articular cartilage proteoglycan synthesis, influx of inflammatory cells, fibrosis and osteophyte formation. When injected together with interleukin 1, TGF-beta enhances IL-1 induced cell-attraction in a synergistic way, while it counteracts IL-1 induced suppression of cartilage PG synthesis. PMID- 8456625 TI - Proteolytic degradation in human articular cartilage: its relationship to stromelysin. AB - Proteolytic degradation of cartilage can in principle occur via the action of proteinases or free radicals, though current evidence favours the enzymic pathway. Link protein can be used as an in situ monitor to identify endogenous proteolytic agents, and its pattern of modification suggests that stromelysin may play a major role in the young, but that additional agents are active in the adult. In cartilage remaining on late-stage osteoarthritic joints, there is less evidence for the action of stromelysin than in normal cartilage, and the tissue appears to be undergoing repair rather than degeneration. PMID- 8456626 TI - Experimental arthritis models in the study of the mechanisms of articular cartilage loss in rheumatoid arthritis. PMID- 8456627 TI - The inhibition of interleukin 1-stimulated cartilage proteoglycan degradation by cysteine endopeptidase inactivators. AB - Cysteine endopeptidase inactivators were tested as inhibitors of interleukin 1 stimulated proteoglycan release from bovine nasal septum cartilage explants. Hydrophilic inactivators showed no inhibition at concentrations up to 100 microM. In contrast, lipophilic inactivators gave significant inhibition, which was both reversible and specific. No effects on interleukin 1 signal transduction were detected, but rates of proteoglycan synthesis were apparently increased. Our results suggest that one or more of the lysosomal cathepsins B, L and S mediate cytokine-stimulated proteoglycan degradation, and the turnover of newly synthesized proteoglycan, but that effective inhibitors must pass through membranes. PMID- 8456628 TI - The role of alpha-1-protease inhibitor (A1PI) in the inhibition of protease activity in human knee osteoarthritis. AB - Alpha-1-protease inhibitor (A1PI) is the most abundant serum protease inhibitor, exhibiting inhibition of proteases known to act in osteoarthritis (OA) and rheumatoid arthritis. We have previously purified and sequenced A1PI synthesized by human articular cartilage and demonstrated in vitro protection from IL-1 induced proteoglycan (PG) degradation at a concentration of 1 mg/ml. In this study, the chondroprotective role of A1PI and possible inhibition of protease activity in OA, IL-1 and LPS-induced and aged normal human knee articular cartilage was investigated by immunohistochemical and in vitro methods. A variable low response to PG-degradation induction and to added A1PI protection of aged normal and OA cartilages was noted, while there was decreased constituative A1PI noted in OA cartilages as compared to normal. PMID- 8456629 TI - In vitro effects of NSAIDs and corticosteroids on the synthesis and secretion of interleukin 1 by human osteoarthritic synovial membranes. AB - The mechanism(s) of action of NSAIDs and corticosteroids in arthritic diseases has been the subject of intensive investigation in recent years. Although NSAIDs and corticosteroids have many effects, their possible ability to modify the disease course in patients has not been fully documented. In an attempt to characterize the mechanism(s) involved in the effect of some NSAIDs in joint diseases, we investigated the effect of three concentrations within the pharmacological (260 micrograms/ml) and therapeutic (26 and 2.6 micrograms/ml) ranges of tiaprofenic acid in the synthesis and release of interleukin (IL-1) alpha and beta in human OA synovial membranes. The effect of tiaprofenic acid was compared to the effect of two other NSAIDs, sodium salicylate (160 micrograms/ml) and indomethacin (1.5 micrograms/ml), and to a corticosteroid, hydrocortisone (0.725 and 7.25 micrograms/ml). This study was carried out using human OA synovium explants incubated in the presence or absence of LPS. In the absence of LPS and at therapeutic concentration, tiaprofenic acid decreased both the synthesis and release of IL-1 beta. A less marked effect of the drug was noted under LPS treatment, and inhibition of the production/secretion of IL-1 beta was found only at pharmacological concentration. Sodium salicylate and indomethacin did not share this action, and demonstrated either no effect or enhancement of IL 1 beta synthesis, respectively, in the presence of LPS. As expected, hydrocortisone demonstrated a marked decrease on IL-1 alpha and IL-1 beta, both in the presence and absence of LPS. These results bring forth new information on the action of these drugs and their effects on the OA pathophysiological process. PMID- 8456630 TI - The in vivo effects of naproxen on canine experimental osteoarthritic articular cartilage: composition, metalloproteinase activities and metabolism. AB - A canine experimental model of osteoarthritis (OA), generated by arthroscopic transection of the anterior cruciate ligament (ACL) of the knee, was used to investigate the in vivo effects of the NSAID naproxen on the course of cartilage degeneration. The drug was given at the time of surgery, or from before surgery, and for 16 weeks after surgery. Analysis of the articular cartilage showed the naproxen was able to significantly suppress the decrease in proteoglycan content and metalloproteinase activities. The results indicate that pharmaceutical agents have the potential to modulate the progression of degenerative joint disease. PMID- 8456631 TI - Interleukin-1 and naproxen down-regulate the expression of IL-1 receptors in cultured human rheumatoid synovial cells (HRSC). AB - Using affinity binding of [125I]-IL-1 alpha and Scatchard analysis, we demonstrate here that exposure of cultured synovial cells (HRSC) to NPX (10(-4) M) for 96 h decreased the binding of IL-1 by 20 to 35%. This effect results from a down-regulation of the IL-1 receptors without change in the apparent binding affinity (kD: 770 pM). Pretreatment of cultures with IL-1 alpha (500 pg/ml) reduced the total binding of [125I]-IL-1 alpha on HRSC by 65%, indicating that IL 1 decreases the expression of its own receptors. PMID- 8456632 TI - Effect of Rumalon (glycosaminoglycan-peptide) on the articular tissue. AB - The effect of glycosaminoglycan-peptide complex (GPC) (Rumalon, made by Robapharm, Switzerland) on cells of the inflammatory periarticular infiltrate and on the articular chondrocytes was studied in experimentally induced papain arthropathy by means of image cytometry and biochemistry. The GPC therapy exhibited some antiinflammatory effect as documented by the reduction of DNA proliferative activity in the inflammatory infiltrate and lowered the activity of hydrolytic enzymes and enzyme inhibitors detected in chondrocytes. PMID- 8456633 TI - Doxycycline protects serum alpha-1-antitrypsin from human neutrophil collagenase. AB - Interstitial collagenases, members of the matrix metalloproteinase family, are key initiators of collagen destruction during various disorders such as rheumatoid arthritis. Recently interstitial collagenases were found to efficiently degrade an additional non-collagenous substrate, the serum alpha-1 antitrypsin (AAT also called alpha-1-proteinase inhibitor or serpin). Serpins are major endogenous inhibitors of serine proteinases, particularly neutrophil elastase. Of relevance to neutrophil-mediated collagen degradation, the tetracycline family of antibiotics are now known to inhibit inhibit mammalian collagenases by a mechanism unrelated to their antimicrobial activity. This study identifies an additional mechanism by which tetracyclines may retard tissue breakdown during inflammatory diseases. Doxycycline, added to the reaction mixture as in concentrations as low as 10 microM, which correspond to levels of the drug readily achieved in vivo, produced detectable inhibition of serpinase activity of neutrophil collagenase, although levels of 50-100 microM or greater were required to reduce AAT degradation more than 75%. The concentration of doxycycline to inhibit 50% (IC50 of serpinase activity) of AAT degradation by neutrophil collagenase was found to approximate 20 microM, a value similar to the IC50 for doxycycline required to inhibit collagen degradation by neutrophil collagenase. Doxycycline was also found to inhibit at cell level neutrophil mediated degradation of AAT. The protection of bodies' AAT-shield from serpinolytic activity of collagenase would result in inhibition of serine proteinases such as neutrophil elastase. Tetracyclines may thus protect matrix constituents from a wider spectrum of neutral proteases than previously recognized, not just from the matrix metalloproteinases collagenase and gelatinase. PMID- 8456634 TI - In vitro construction of cells-containing implants for articular cartilage regeneration. AB - Regeneration of destroyed articular cartilage can be induced by transplantation of cartilage cells into the defects. The best results are obtained by the use of either fetal allogeneic cells or autogenic ones. Induction of chondrogenesis in residual mesenchymal cells is optimal for obtaining large amounts of autogenic chondrocytes. Further modification of the technique is needed to reconstruct large defects. The cells are grown on biodegradable scaffolds and are later implanted into joint defects. PMID- 8456635 TI - Cellular aspects on treatment of cartilage injuries. AB - Cellular aspects on articular cartilage growth and development are discussed. Cells with chondrogenic potential are described and current treatment models for cartilage injuries are considered. A rabbit model for treatment of articular cartilage defects with autologous cultured and transplanted chondrocytes for treatment of knee cartilage defects in humans are discussed. PMID- 8456636 TI - Human meniscus transplantation. AB - The short term results of 15 cryopreserved non-tissue-antigen matched meniscus transplantations are described. The clinical outcome is satisfactory. Histological and histochemical studies showed that meniscuschondrocytes can survive cryopreservation and transplantation. PMID- 8456637 TI - In situ hybridisation for decorin mRNA in rabbit synovium during antigen-induced arthritis. AB - Decorin mRNA was localised primarily in the lining layer of normal rabbit synovium. The distribution changed during the development of antigen-induced arthritis. It became more abundant deeper in the synovium and may be correlated with the progressive increase in the deposition of collagen. PMID- 8456638 TI - Osteoarthritis in rhesus macaques: assessment of cartilage matrix quality by quantitative magnetic resonance imaging. AB - To assess cartilage quality with anatomical location and extent of osteoarthritis (OA), magnetic resonance imaging (MRI) of the knee joint from rhesus monkeys was performed. MRI measurements--T1 and T2 relaxation times, proton density and cartilage thickness were taken from 8 equal segments of articular cartilage volumes extending from anterior to posterior edge of 1 mm sagittal slices. To grade the severity of OA in each quadrant of the knee joint a modified Mankin score was applied on the histological sections. Our results suggest that MR relaxation times and proton density values vary with the severity of osteoarthritis. PMID- 8456639 TI - A magnetic resonance imaging study of joint degeneration in the guinea pig knee. PMID- 8456640 TI - Development of immortalized human articular cartilage cell lines. AB - Human articular cartilage cells were transfected with the t.-sensitive polyomavirus large T antigen of SV40. Several immortalized chondrocyte cell lines were obtained. The types of acidic polysaccharides and of collagen synthesized suggest dedifferentiation in the in vitro culture system used afterwards to obtain large numbers of cells. PMID- 8456641 TI - Altered structure-function relationships for articular cartilage in human osteoarthritis and an experimental canine model. AB - A review of the structure-function relationships for normal articular cartilage is provided. This provides the foundation for understanding the roles played by collagen, proteoglycan and water in determining the material properties of the tissue. A summary of biomechanical and compositional changes in human osteoarthritic cartilage is also presented. Finally, the results from our recent interdisciplinary study on an experimental osteoarthritis model is described, and new hypotheses are proposed on the initiating factors responsible for the increase of tissue hydration. At present, it appears that microstructural alterations, rather than compositional changes, of the collagen-proteoglycan solid matrix are responsible for the early increase of hydration and the deterioration of biomechanical properties of articular cartilage. PMID- 8456642 TI - Osteoarthritis in the human knee: a dynamic process of cartilage matrix degradation, synthesis and reorganization. AB - The matrix of articular cartilage undergoes degenerative changes in osteoarthritis which involve a number of matrix molecules. The structural and mechanical integrity is organized around the composite collagen II, IX, XI fibrillar organization. The small proteoglycan decorin that binds to these fibrils may influence their structure and mechanical properties. Aggrecan interacts indirectly via hyaluronic acid and possibly directly through unknown mechanisms. When collagen is cleaved at the articular surface in early osteoarthritis, decorin and aggrecan are lost. Increases in decorin and aggrecan content occur deeper in the cartilage. This is accompanied by evidence for increased formation of collagen fibrils and increased degradation and synthesis of aggrecan and type II collagen. The net contents of these proteoglycan per tissue do not, however, change until advanced degeneration occurs. These degradative processes are likely catalyzed by metalloproteinases and cysteine proteases. Cartilage exhibits significant capacity for remodelling which may be enhanced by therapeutic management of this process. PMID- 8456643 TI - Mechanisms of cartilage destruction in joint inflammation. PMID- 8456644 TI - Synovial fluid analyses detect and differentiate proteoglycan metabolism in canine experimental models of osteoarthritis and disuse atrophy. AB - Canine experimental models of osteoarthritis (OA) and disuse atrophy were used to study cartilage metabolism. The synovial fluids from the OA joints showed elevated levels of keratan sulfate (KS) epitope and link protein, indicating increased catabolism. Analysis of fluids from joints with disuse atrophy showed high levels of KS epitope, but no increase in link protein. Quantitation of a novel chondroitin sulfate (3B3) epitope showed it to be present only in the synovial fluids and articular cartilage of the OA joints. The results indicate that these may be important indicators, or markers, of degenerative joint disease. PMID- 8456645 TI - Humoral and cell-mediated sensitivity to cartilage constituents in mice with antigen-induced arthritis. AB - Serum antibodies against native collagen type II and cartilage proteoglycans as well as proliferative responses of spleen lymphocytes to these antigens were evidenced during the progression of antigen-induced arthritis in mice. Because there were some correlations to the severity of arthritis, it is suggested that autoimmunity to cartilage constituents play a role for the persistence of the joint inflammation and cartilage destruction in this experimental model of chronic arthritis. PMID- 8456646 TI - Are antibodies reactive with chondrocyte proteins enriched in synovial fluids of patients with rheumatoid arthritis? AB - In this study we examined the reactivity of synovial fluid (SF) antibodies (Abs) from patients with rheumatoid arthritis (RA) against chondrocyte proteins. The levels of IgG, IgM and IgA in the synovial fluids varied from patient to patient, but were similar to the levels found in each individual's serum. Although the Abs in SF and serum of RA patients reacted with several molecular weight classes of chondrocyte proteins, this reactivity was very low. Synovial fluid and serum Abs from the same patients reacted with similar chondrocyte proteins and to a similar extent, suggesting that the level of Abs reactive with chondrocyte proteins is not enriched in the SF. These data demonstrate that SF from RA patients contain high levels of Abs, however, there is very little reactivity with chondrocyte proteins beyond that observed in serum of normal and RA patients. PMID- 8456647 TI - The metabolic response of articular cartilage to abnormal mechanical loading induced by medial or lateral meniscectomy. AB - The effects of medial versus lateral meniscectomy on articular cartilage (AC) of adult sheep was investigated. In vitro incorporation of 35S into proteoglycans (PGs) and their release into media was used to assess cartilage metabolism. Lateral meniscectomy produced higher loss of PGs from AC and lower 35S-PG biosynthesis than for AC from medial meniscectomized joints. These findings were consistent with the proposed role of the lateral meniscus in joint mechanics. PMID- 8456648 TI - Effects of long-term running exercise on canine femoral head articular cartilage. AB - After long-term running program (40 km/day) anterior and posterior tissue samples from canine femoral head were labeled ex vivo in the presence of 35S-SO4. Sulfate incorporation rates did not differ between runner and control groups. The statistically significant changes in runners included a decreased uronic acid concentration (p < or = 0.02) and proportion of extractable proteoglycans (p < or = 0.05) as well as increased concentration of tissue uronic acid after 4 M GuCl extraction (p < or = 0.05) in the posterior area. These results support an idea of strengthened cartilage tissue after this kind of motion and load. PMID- 8456649 TI - Merrill C. Sosman Lecture. The Auger process: a therapeutic promise? PMID- 8456650 TI - A history of the AMA section council on radiology. PMID- 8456651 TI - Eugene J. Keefe Memorial Lecture. The Canadian health care system: an overview. AB - Canada has 21 years of experience with a national health care insurance program. This lecture describes the program, its evolution, financing, and attitudes and perceptions of the consumer, the provider (physicians and hospitals), and the funding agencies (governments). Comparisons, where appropriate, with the system in the United States are incorporated. PMID- 8456652 TI - Helical (spiral) CT of the abdomen. AB - Since its clinical introduction in the mid 1970s, techniques for CT have undergone many changes that have dramatically altered how CT scans are obtained. Helical (spiral) CT allows for faster acquisition of truly volumetric CT data than is possible with conventional scanners. Routine helical CT of the abdomen is now possible because of three major technical refinements: the development of the slip-ring gantry, improved detector efficiency, and greater tube cooling capability. This article reviews the technical principles that govern helical CT, the potential advantages and disadvantages of this technique, and initial clinical experience with helical CT of the abdomen. PMID- 8456653 TI - Diseases of the intracranial meninges: MR imaging features. AB - Although the meninges are often thought of simplistically as a connective tissue sac that contains the CSF and the contents of the CNS, they are far more complex. Anatomically, they comprise several layers. Pathologically, numerous disease processes may affect the meninges; different processes may even involve different areas of the meninges. These factors all influence the MR imaging characteristics of meningeal lesions. This review briefly discusses the anatomy of the meninges, the MR imaging technique when meningeal disease is suspected, and the appearance of the normal meninges. It then focuses on tumors, infections, cysts, and other lesions that primarily involve the meninges, excluding lesions that secondarily involve the meninges. PMID- 8456654 TI - Functional endoscopic sinus surgery: anatomy, CT screening, indications, and complications. PMID- 8456655 TI - Appearance of the inferior phrenic artery and vein on CT scans of the chest: a CT and cadaveric study. AB - OBJECTIVE: Central linear densities are often seen at the level of the diaphragm on CT scans of the chest. To determine the cause of these densities, we evaluated helical CT scans and correlated the results with the findings from a study of cadavers. SUBJECTS AND METHODS: Forty patients who had normal findings on conventional CT scans had helical CT of the entire chest. For the cadaveric study, we examined the lung bases and extrapleural spaces on the diaphragmatic surface in 22 formalinized cadavers. RESULTS: On helical CT scans, linear densities extending laterally from the mid-part of the right side of the inferior vena cava and from the posterior margin of the left ventricle were seen on the right side of the chest in 12 subjects (30%) and on the left side in 17 subjects (42%). In the cadavers, the inferior phrenic artery and the accompanying vein ran over the diaphragmatic dome in the extrapleural space from the region of the inferior vena cava on the right and from the posterior margin of the left ventricle on the left. These supradiaphragmatic vessels were seen on the right side in 10 cadavers (45%) and on the left side in four cadavers (18%). CONCLUSION: We conclude that these linear densities at the level of the diaphragm on CT scans of the chest represent the inferior phrenic artery and vein. PMID- 8456656 TI - The superior pericardial sinus: normal appearance on gradient-echo MR images. AB - OBJECTIVE: The purpose of this study was to describe and explain the normal appearance of the superior pericardial sinus (the retroaortic extension of the superior pericardial recess) on gradient-recalled-echo (GRE) MR images. This is important clinically because on some GRE images the superior pericardial sinus may have a signal like that of flowing blood, which could be mistaken for an aortic dissection or an anomalous vascular structure. SUBJECTS AND METHODS: Six patients had MR imaging for evaluation of the mediastinum. In two cases, CT scans were also obtained. Both T1- and T2-weighted axial, spin-echo, ECG-gated MR images were obtained in all cases. The superior pericardial sinus was imaged with axial gradient-recalled acquisition in the steady state (GRASS) by using flip angles between 5 degrees and 60 degrees. The nature of the signal of the superior pericardial sinus on GRASS images was further studied in one patient by using spoiled GRASS (SPGR), GRASS with an inferior saturation pulse, GRASS with a slice thickness that encompassed the entire superior pericardial sinus, and cine GRASS sequences. RESULTS: The superior pericardial sinus was visualized well in all six patients. It had low signal on T1-weighted images and high signal on T2-weighted images. The signal of the sinus on T2-weighted images was heterogeneously high in three of six cases. On GRASS and cine images with flip angles less than 20 degrees, the signal of the superior pericardial sinus was similar to that of flowing blood. The sinus also had high signal on SPGR images with flip angles less than 10 degrees. No decrease in the signal of the sinus was seen on GRASS images obtained with an inferior saturation pulse. On SPGR and GRASS images obtained with the same parameters, the signals of the superior pericardial sinus were similar. When the slice thickness of the GRASS sequence was increased to encompass the entire sinus without an inferior saturation pulse, little or no decrease in signal occurred. CONCLUSION: On flow-sensitive GRE MR images obtained with a low flip angle and moderate TE, the superior pericardial sinus has high signal similar to that of flowing blood. This is a reflection of the high proton density and long T2* of pericardial fluid, and not a consequence of flow or steady-state free precession. Radiologists must be aware of this phenomenon in order to avoid misdiagnosis of aortic dissection or confusion with a vascular structure. PMID- 8456657 TI - Brown tumor. PMID- 8456658 TI - Adult-onset pulmonary tuberculosis: findings on chest radiographs and CT scans. AB - Adult-onset pulmonary tuberculosis refers to primary tuberculous infection occurring initially in adults. The decreasing exposure in childhood, owing to careful public health measures and the advent of antituberculous chemotherapy, has resulted in later initial exposure to tuberculosis and an increased likelihood of susceptibility to tuberculosis during adulthood [1-3]. In addition, chest radiographs typically show a pattern more consistent with primary infection in pulmonary tuberculosis associated with AIDS. In this essay, we illustrate the spectrum of radiographic and CT findings of adult-onset pulmonary tuberculosis in patients without AIDS. PMID- 8456659 TI - Pulmonary venoocclusive disease: CT findings before and after single-lung transplantation. PMID- 8456660 TI - Localization of pulmonary nodules for thoracoscopic resection: use of needle/wire breast-biopsy system. PMID- 8456661 TI - Diagnosis of acute appendicitis: value of unenhanced CT. AB - OBJECTIVE: Two hundred eleven patients with acute pain in the right lower quadrant had CT without oral or IV contrast material. The CT examination required less than 5 min to perform and interpret. We assessed the efficacy of this limited CT examination in identifying patients with acute appendicitis who required emergency laparotomy. SUBJECTS AND METHODS: Unenhanced CT of the lower abdomen was performed in 211 patients with lower abdominal pain of uncertain origin (130 women and 81 men 4-91 years old). Scans were obtained by using 10-mm collimation at 10-mm intervals from the L3 level to the symphysis pubis without IV or oral contrast material. Twenty-two to 30 images per patient were obtained, depending on the size of the patient. On average, the entire examination took less than 5 min to complete. Prospective diagnoses based on CT findings were compared with surgical results and clinical follow-up. RESULTS: Unenhanced CT was an accurate imaging technique for the initial examination of patients with suspected acute appendicitis. The accuracy was 93%. The sensitivity was 87%, the specificity was 97%, the positive predictive value was 94%, and the negative predictive value was 93%. CONCLUSION: This study shows that unenhanced CT is a useful test to diagnose appendicitis in patients with acute abdominal pain in the right lower quadrant. PMID- 8456662 TI - Esophageal perforation: CT findings. AB - OBJECTIVE: Esophageal perforation is a life-threatening condition that can be quickly diagnosed on the basis of findings on contrast esophagograms when the typical signs and symptoms of vomiting, chest pain, and subcutaneous emphysema occur. If the clinical features are atypical, CT may be performed early in the clinical course. Thus, recognition of the CT findings of esophageal perforation is important. MATERIALS AND METHODS: We reviewed the CT scans of 12 patients with esophageal perforation. The site of perforation was the cervical esophagus in three and the thoracic esophagus in nine. The causes of the perforations were neoplastic (four patients), idiopathic (three patients), iatrogenic (three patients), and traumatic (two patients). RESULTS: CT abnormalities included esophageal thickening in nine patients, periesophageal fluid in 11 patients, extraluminal air in 11, and pleural effusion in nine. The site of the perforation was visible on the CT scan in two patients. In four patients (33%), CT findings were the first indication of esophageal perforation. CONCLUSION: For patients who have atypical signs and symptoms, CT scans optimally define the extraluminal manifestations of esophageal perforation. Extraesophageal air is the most useful finding. The CT findings may be the first indication of the diagnosis. PMID- 8456663 TI - Endosonographic evaluation of patients with anal incontinence: findings and influence on surgical management. AB - OBJECTIVE: Endosonography using an anal probe gives detailed information about the internal and external anal sphincters. The goals of this study were to evaluate findings at anal endosonography in patients with anal incontinence and to study whether endosonography might replace needle electromyographic mapping in providing information on the external anal sphincter. Furthermore, we compared the type of sphincter damage found by endosonography with the anal canal pressures and studied the value of endosonography for selecting the most effective surgical treatment. SUBJECTS AND METHODS: Forty-eight patients with incontinence for either gas (17 patients) or feces (31 patients) were studied. Nineteen patients had idiopathic incontinence, 29 were incontinent as a result of previous obstetrical or surgical trauma. Endosonography and measurement of anal canal pressures were performed in all patients; 40 had needle electromyography. The endosonograms were evaluated without knowledge of the clinical findings, and the endosonographic findings were correlated with the results of needle electromyography, with the anal pressures, and with the type of surgery subsequently performed. In 30 patients, surgery was subsequently planned on the basis of the results of endosonography and the anophysiologic examinations. RESULTS: Endosonograms showed defects of the external sphincters in 27 patients, 12 of whom had internal sphincter defects also. One patient had an abnormal thinning of the external sphincter. Eight patients had defects of the internal sphincter as the only finding. Twenty-two of the patients with sonographically detected defects or thinning of the external sphincter had electromyography, which showed defects of the external sphincter in 18; four defects in the middle and upper anal canal were not found. The sphincteric defects found by endosonography did not correlate with the anal canal pressures. Sphincter reconstruction was offered to most patients who had damage to the external sphincter; patients with isolated defects in the internal sphincter or intact internal and external sphincters were offered a number of other surgical procedures. CONCLUSION: Endosonography can be used in place of the invasive electromyographic mapping for detecting defects of the external sphincter, and endosonography also gives additional information on the internal sphincter, which cannot be obtained by other means. No correlation between the anal pressures and the type of sphincter damage found by endosonography can be demonstrated. The main reason for performing endosonography is to detect defects in the external sphincter, for which surgical reconstruction is most likely to be done, whereas visualization of internal sphincter defects seems to have no influence on surgical management and does not lead to any specific treatment. PMID- 8456664 TI - Functional disorders of the anus and rectum: findings on defecography. AB - In the past decade, interest in the anorectal region and the mechanism of continence and defecation has been increasing. Subsequently, techniques to visualize the anorectum have been introduced; evacuation proctography and defecography have been used to describe the dynamic radiologic evaluation of this area. Also, developments in anorectal manometry, electromyography, and transrectal sonography have renewed interest in defecography, particularly in categorizing the functional disorders including rectocele, intussusception and prolapse, enterocele, descending perineum syndrome, dyskinetic puborectalis muscle, solitary rectal ulcer syndrome, and incontinence. PMID- 8456665 TI - Detection of focal hepatic lesions with spiral CT: comparison of 4- and 8-mm interscan spacing. AB - OBJECTIVE: The objective of this study was to determine if spiral CT with 4-mm interscan spacing results in increased confidence in or rate of detection of focal hepatic lesions when compared with spiral CT with 8-mm interscan spacing. MATERIALS AND METHODS: Spiral CT scans of the liver of 42 consecutive patients with suspected hepatic disease were independently reviewed by three senior radiologists in two sets: one set was reconstructed with 8-mm interscan spacing and one set was reconstructed with 4-mm interscan spacing. The slice thickness was 8 mm for both data sets. The number and sizes of focal hepatic lesions were documented. RESULTS: Thirty-three of the 42 patients had least one focal lesion. The lesion size varied from 2 mm to 21 cm. When 8-mm interscan spacing was used, 297 lesions were detected (212 were considered definite). When 4-mm interscan spacing was used, 318 lesions were detected (258 were considered definite). Therefore, 7% more lesions were detected with 4-mm interscan spacing than with 8 mm interscan spacing (p = .05), and 22% more were diagnosed definitively (p < .01). If lesions larger than 4 cm are excluded, 10% more lesions were detected with 4-mm interscan spacing, and 33% more were diagnosed definitively. Of the lesions detected exclusively with 4-mm interscan spacing, 69% were less than 1.0 cm in diameter. CONCLUSION: Spiral CT with smaller interscan spacing (4 instead of 8 mm) results in increased confidence in and rate of detection of focal liver lesions. The additional benefit is most significant with smaller lesions. PMID- 8456666 TI - Spiral CT of the liver. AB - The usefulness of CT in the detection and characterization of hepatic disease is well established. Requirements for high-quality examinations include rapid bolus infusion of iodinated contrast materials, rapid acquisition of axial images, and minimal respiratory motion in the patient. These requirements are satisfied in spiral or helical CT. Spiral CT is the latest advance in rapid scanning techniques. In the spiral scan mode, image acquisition is continuous, as patients are advanced at a constant rate through the CT gantry. This eliminates the interscan delay and the gap between scan slices. Because the scan can be completed within a single breath-hold, respiratory misregistration of adjacent scan slices is eliminated. These factors also contribute to high-quality multidimensional displays (e.g., coronal and sagittal views). In this pictorial essay, we illustrate the advantages and applications of spiral CT scanning for imaging the liver. PMID- 8456667 TI - Therapeutic percutaneous aspiration of hepatic abscesses: effectiveness in 25 patients. AB - OBJECTIVE: The objective of this study was to evaluate the effectiveness of sonographically guided needle aspiration and systemic antibiotic therapy for the treatment of hepatic abscesses. SUBJECTS AND METHODS: From June 1989 to September 1991, sonographically guided needle aspiration and systemic antibiotics were used to treat 25 consecutive patients with 25 hepatic abscesses. Among 36 patients with hepatic abscesses who were admitted to the hospital during that time, six had antibiotic therapy only; of these, three had microabscesses, two had abscesses less than 3.0 cm in diameter, and one refused needle aspiration. Four patients had surgical external drainage (three had cholelithiasis in addition to hepatic abscesses, and one did not respond to needle aspiration). Two patients treated in 1989 had drainage via an indwelling catheter, which was the preferred method at that time. The remaining 24 patients and one patient who had needle aspiration followed by surgical drainage made up the study group. Seventeen of the hepatic abscesses were caused by pyogenic organisms, six by amoeba, and two by unknown organisms. Eighteen abscesses (72%) were aspirated once, four (16%) were aspirated twice in 8 days, two (8%) were aspirated three times in 14 days, and one (4%) was aspirated four times in 10 days. Persistent fever, pain and tenderness in the right upper quadrant, and leukocytosis were the indications for multiple aspirations. Follow-up sonography was performed to evaluate the outcome of treatment. RESULTS: In 16 cases (64%), the abscesses disappeared within a mean of 84 days. In eight cases (32%) with only partial follow-up, the patients were asymptomatic at the time of discharge and the abscesses were markedly smaller on the last follow-up sonograms (mean, 43 days). One patient (4%) did not respond to aspiration and had surgical drainage. The length of hospitalization varied from 5 to 42 days (mean, 22 days). In patients who became afebrile during the treatment, the fever had lasted from 0 to 10 days (mean, 3 days). Only one patient had a complication of the procedure, a pleural effusion that was treated conservatively. CONCLUSION: Our results show that sonographically guided needle aspiration combined with antibiotic therapy is effective as the initial treatment for hepatic abscesses. PMID- 8456668 TI - Hysterosalpingography before and after myomectomy: clinical value and imaging findings. AB - OBJECTIVE: Myomectomy is being performed increasingly for the treatment of menorrhagia and infertility. The purpose of this study was to describe the findings at hysterosalpingography before and after myomectomy and to correlate the findings with the operative technique and observations at surgery. This study also examined the value of hysterosalpingography in planning surgery, as well as in detecting postoperative complications and residual fibroids. MATERIALS AND METHODS: The study group comprised 32 patients who were consecutively referred for hysterosalpingography after myomectomy. The indications for myomectomy were infertility in all cases, associated with menorrhagia in 20, pelvic pain in 15, and urinary frequency in eight. Eighteen of the 32 patients also had hysterosalpingography before surgery. The hysterosalpingographic findings were reviewed without knowledge of the clinical findings and then correlated with surgical and pathologic findings. RESULTS: Preoperative hysterosalpingograms showed enlargement and/or distortion of the uterine cavity in 13 of 14 patients who had submucous fibroids or mural fibroids with a submucous component (mural/submucous fibroid). Cornual asymmetry was seen in seven of 18 patients, the result of an adjacent fibroid deforming one bilaterally in another two. In all four patients, tubal patency was shown after myomectomy. Intracavitary filling defects consistent with submucous or mural/submucous fibroids were found in 12 of 18 patients. After myomectomy, these defects resolved in eight cases; in the remaining four, persistent filling defects suggested residual submucous enlargement of the uterine cavity in only two of 32 patients; in both, residual mural and/or submucous fibroids were shown on sonography after surgery. Major distortion of the cavity after surgery was found in four patients; it was caused by filling defects consistent with residual submucous fibroids in two and by major synechiae in two. Diverticula at the site of resection of submucous fibroids were found in six patients. Major synechiae were found in two patients, resulting in unilateral or bilateral tubal occlusion. CONCLUSION: Hysterosalpingography before myomectomy can assist the surgeon in planning the surgical approach by showing the presence, size, and location of submucous fibroids and concomitant tubal disease. Hysterosalpingography after myomectomy shows residual fibroids and complications of surgery, such as synechiae and diverticula, that may affect further treatment. PMID- 8456669 TI - Endometrial abnormalities associated with tamoxifen therapy for breast cancer: sonographic and pathologic correlation. AB - OBJECTIVE: Tamoxifen is widely used to treat breast carcinoma in postmenopausal women. Previous studies have suggested an increased prevalence of endometrial carcinoma and polyps after treatment with tamoxifen. We correlated findings on pelvic sonograms with pathologic findings in a group of patients treated with tamoxifen. MATERIALS AND METHODS: We reviewed the pelvic sonograms and medical histories of 14 postmenopausal women with breast carcinoma who were being treated with tamoxifen. Pathologic correlation was available in the 11 cases in which adequate tissue was obtained. Coexisting pathologic changes were found in seven patients. Pathologic examination showed a total of 18 endometrial abnormalities, including nine cases of uterine polyps, four cases of hyperplasia, two cases of endometritis, one proliferative endometrium, one inactive endometrium, and one case of carcinoma. RESULTS: Sagittal sonograms of all 11 patients with pathologic correlation showed abnormal endometrial thickening measuring more than 7 mm. The sonographic appearance of the endometrium in these patients included hyperechoic, homogeneous tissue; hyperechoic tissue with multiple, small cystic spaces; heterogeneous tissue with small cystic spaces; and solid tissue that was heterogeneous. Small cystic spaces were seen in all cases of polyps. Six of the nine cases of polyps were associated with other endometrial abnormalities also. The single case of endometrial carcinoma appeared solid and heterogeneous on sonography; however, further pathologic examination of the surgical specimen showed a coexisting polyp. CONCLUSION: Tamoxifen therapy is associated with several findings on sonograms of the uterus. Because several pathologic findings frequently coexist, sonography is of limited use in the diagnosis of specific abnormalities. PMID- 8456670 TI - Dupuytren's contracture: MR imaging findings and correlation between MR signal intensity and cellularity of lesions. AB - OBJECTIVE: Dupuytren's contracture is a common fibrosing disorder of the hand which often results in progressive and debilitating flexion contractures of the fingers. Recurrence after surgical release is common and may be related, in part, to the cellularity of the lesion. We describe the MR appearance of Dupuytren's contracture and correlate signal characteristics with the degree of cellularity of the lesion. SUBJECTS AND METHODS: A total of 11 hands in 10 patients were studied. All patients had surgical resection after MR imaging (median interval, 3 days). The surgical and pathologic findings were correlated with the MR findings. The signal characteristics of the lesions were correlated with the histologic findings. RESULTS: We found that MR imaging was accurate for detecting Dupuytren's contracture and depicting its extent. The lesions include subcutaneous nodules, usually at the level of the distal palmar crease, and cords that lie parallel and superficial to the flexor tendons. The cords had a uniformly low signal intensity (similar to the signal intensity of tendon) on both T1- and T2-weighted images in 18 of 22 cases, whereas the remaining four cases had a low to intermediate signal intensity on T1-weighted images (a slightly higher signal intensity than that of tendon) and a low signal intensity on T2-weighted images. Histologically, the cords were hypocellular and composed of dense collagen. Most nodules had an intermediate signal intensity (similar to that of muscle) on both T1- and T2-weighted images (10 of 13 cases), usually stippled with focal areas of lower signal intensity. Histologically, these nodules were mostly cellular. Three of the nodules had a low signal intensity on both T1- and T2-weighted images and were hypocellular histologically. CONCLUSION: We conclude that MR imaging can be used to define palmar involvement in Dupuytren's contracture. The signal characteristics of the lesions correlate with the degree of cellularity of the lesions as seen histologically. The ability to assess preoperatively the cellularity of lesions of Dupuytren's contractures may be of prognostic significance, because highly cellular lesions tend to have higher rates of recurrence after surgery than do hypocellular lesions. PMID- 8456671 TI - Three-compartment wrist arthrography: correlation of pain site with location of uni- and bidirectional communications. AB - OBJECTIVE: Our objective was twofold: (1) to determine whether the site of patients' pain correlates with abnormal findings on three-compartment wrist arthrograms and (2) to determine whether the directional nature (uni- vs bidirectional) of communication(s) between adjacent wrist joint compartments shown on three-compartment wrist arthrograms correlates with the presence and site of pain. MATERIALS AND METHODS: We retrospectively studied 462 three compartment wrist arthrograms of 458 patients. The patients were divided into four groups according to the site of pain, the correlation of that site with the site of the communication, and the directional characteristics of communications shown on the arthrogram: (1) exact correlation between site of pain and arthrographic findings, (2) correlation only between side of pain (ulnar or radial) and arthrographic findings, (3) ambiguous correlations (e.g., multifocal, midline, or diffuse pain), and (4) no correlation between site of pain and arthrographic findings. RESULTS: In 191 patients (42%), 226 intercompartmental communications were detected (51 uni- or 173 bidirectional). One hundred sixty one patients had only one communication (uni- or bidirectional), and 30 patients had more than one (uni- and/or bidirectional) communication for a total of 65 defects. Regardless of the directional nature of the communication, no positive association between sites and/or the side of symptoms and sites of communications was demonstrable. However, a potential association appears to exist between ulnar sided pain and combined lunotriquetral and triangular fibrocartilage tears. CONCLUSION: Our results suggest that the directional nature of interjoint communications has little or no clinical significance. Thus, with the exception of seeking the cause of ulnar-sided pain, our results question the usefulness of routine arthrography for correlating sites of patients' symptoms and individual interjoint communications. PMID- 8456672 TI - MR imaging of the knee: can changes in the intracapsular fat pads be used as a sign of synovial proliferation in the presence of an effusion? AB - OBJECTIVE: Synovial proliferation is difficult to detect on MR images when joint effusions are present. The objective of this study was to assess the efficacy of MR changes in intracapsular fat pads (prefemoral, quadriceps, Hoffa's) as a sign of synovial proliferation in patients with knee effusions. MATERIALS AND METHODS: MR images were obtained in 70 patients with knee effusions. An effusion was considered present if the suprapatellar bursa was distended 1 cm in anterior to posterior diameter on T2-weighted sagittal images. The experimental group consisted of 32 patients with proliferative effusions (effusions associated with synovial proliferation) diagnosed on the basis of histologic or microbiologic data or strict rheumatologic criteria. This group comprised 11 patients with pigmented villonodular synovitis, six with rheumatoid arthritis, one with psoriatic arthritis, three with hemosideric arthritis, and 11 with septic arthritis. The control group comprised 38 subjects with knee effusions who had no arthroscopic evidence of synovial proliferation. After determining the MR criteria of proliferative effusion, two observers who had no knowledge of these cases evaluated abnormalities of the intracapsular fat pads seen on sagittal intermediate-weighted midline MR images. RESULTS: Characteristic changes in the fat pads were noted on MR images in patients with proliferative synovial effusions. Scalloping or truncation of the prefemoral fat pad was 77% sensitive and 95% specific as a predictor of proliferative effusion. Defects and displacement of Hoffa's fat pad had a sensitivity of 57% and a specificity of 99%, and nonvisualization or irregular margins of the quadriceps fat pad had a sensitivity of 61% and a specificity of 100%. CONCLUSION: Characteristic changes in intracapsular fat pads seen on MR images of patients with proliferative effusions can help distinguish these patients from those with effusions without synovial proliferation. PMID- 8456673 TI - Prognostic significance of nonvisualization of the fetal stomach by sonography. AB - OBJECTIVE: To establish the prognostic significance of nonvisualization of the fetal stomach, we prospectively studied the course and outcome of 31 pregnancies in which a normal fluid-filled fetal stomach could not be seen during sonographic examination after 14 weeks' gestation. SUBJECTS AND METHODS: Between April 1989 and May 1991, 7200 sonographic examinations of fetuses after 14 weeks' gestation were done at our hospital. In 31 pregnancies (0.4% of all scans), a normal fluid filled fetal stomach could not be seen on one or more sonograms after 14 weeks' gestation (range, 14-40 weeks; mean, 22 weeks). The following data were recorded for each examination: gestational age, visualization of the stomach, other fetal abnormalities, and volume of amniotic fluid. In each pregnancy, the average number of sonograms obtained was three (range, one-five). The fetal stomach was regarded as abnormal if the stomach bubble was absent or remained very small and unchanged for at least 45 min during sonography. RESULTS: The outcome was normal in 16 cases. The 15 abnormal outcomes included spontaneous fetal or neonatal death in five, pregnancy terminations in three, and persistent postnatal disability in seven. In 15 pregnancies (48%) lack of visualization of the fetal stomach was the only significant abnormal sonographic finding, but an abnormal outcome occurred in three. In 12 pregnancies, nonvisualization of the fetal stomach was a transient finding, yet three of those pregnancies resulted in persistent postnatal disability, and one was terminated because of severe maternal preeclampsia. A normal fluid-filled stomach was seen on the next sonogram in 15 cases, but five had an abnormal outcome. Only one of the four pregnancies in which a normal stomach was not seen on any subsequent sonogram had an abnormal outcome. Six of seven pregnancies with oligohydramnios had an abnormal outcome, and all three cases with polyhydramnios had an abnormal outcome. The prevalence of abnormal outcome was 88% when additional sonographic abnormalities were observed, but 20% when no other sonographic abnormality was seen. The overall prevalence of abnormal outcome when the fetal stomach was not visualized was 48%. CONCLUSIONS: Not all fetuses with a nonvisualized stomach after 19 weeks' gestation have a poor outcome. Not all fetuses with a transiently nonvisualized stomach have a normal outcome. PMID- 8456674 TI - Pulse oximetry-gated acquisition of cardiac MR images in patients with congenital cardiac abnormalities. PMID- 8456675 TI - Asymmetric renal size in autosomal recessive polycystic kidney disease: a unique presentation. PMID- 8456676 TI - Isolated abducens nerve palsy: MR imaging findings. AB - The abducens nerve, the sixth cranial nerve, innervates the lateral rectus muscle of the eye and is responsible for lateral horizontal ocular movement. A wide variety of abnormalities, both primary to the nerve itself and secondarily involving the nerve, can paralyze the abducens nerve. MR imaging offers the best opportunity to detect the underlying abnormality causing abducens nerve palsy. In this pictorial essay, we illustrate the MR imaging features of numerous conditions that cause isolated abducens nerve palsy. PMID- 8456677 TI - Imaging of neurologic complications associated with pregnancy. AB - The occurrence of a neurologic event during pregnancy or the puerperium may have devastating consequences for mother and child. It is imperative that the radiologist be familiar with the entities likely to be encountered in pregnancy so that these patients can be examined rapidly and efficiently. The importance of early and accurate diagnostic imaging is underscored by the fact that most patients are otherwise young and healthy, and prompt institution of appropriate therapy can result in complete recovery. In this report, we illustrate some of the more common neurologic complications that occur during pregnancy and the immediate postpartum period. PMID- 8456678 TI - Extracranial cerebellum: CT and MR findings of an unusual variation of the Chiari II malformation. PMID- 8456679 TI - Paraganglioma of the filum terminale: MR findings. PMID- 8456680 TI - Spinal epidural hematoma in a patient with lupus coagulopathy: MR findings. PMID- 8456681 TI - Role of femoral vessel catheterization and altered hemostasis in the development of extraperitoneal hematomas: CT study in 44 patients. AB - OBJECTIVE: To ascertain the role of femoral vessel catheterization and altered hemostasis in the development of extraperitoneal hematomas, we evaluated CT scans to study the locations of extraperitoneal hematomas in three distinct clinical settings: (1) after femoral vessel catheterization with concurrent altered hemostasis due to anticoagulant, thrombolytic, and/or antiplatelet therapy (catheterized-altered hemostasis group); (2) after femoral vessel catheterization without altered hemostasis (catheterized group); and (3) with no history of femoral vessel catheterization, with or without altered hemostasis caused by a bleeding diathesis or pharmacotherapy (uncatheterized group). MATERIALS AND METHODS: Forty-four patients were identified who had CT evidence of extraperitoneal hematomas. Twenty-four were in the catheterized-altered hemostasis group, one was in the catheterized group, and 19 were in the uncatheterized group. CT scans were evaluated for anatomic subspace involvement by hemorrhage and for the presence or absence of contiguity between the hematoma and the femoral vessels. RESULTS: Bilateral hematomas were present in six of 24 patients in the catheterized-altered hemostasis group and in four of 19 patients in the uncatheterized group. We found no significant difference between the catheterized-altered hemostasis and the uncatheterized groups regarding the proportion of cases involved at any individual retroperitoneal site (p > .05). The mean number of hematoma sites in the catheterized-altered hemostasis group (4.3) was not significantly different from the mean number in the uncatheterized group (3.7) (p > .05). Contiguity between the sites of hematoma and the punctured femoral vessels was present in 75% of the patients in the catheterized-altered hemostasis group; contiguity between the hematoma and a groin was seen in 58% in the uncatheterized group. Twenty-two of 24 patients in the catheterized-altered hemostasis group had CT findings of subcutaneous fat infiltration in the groin; however, six of 19 patients in the uncatheterized group also had this finding, indicating that its presence does not always represent changes caused by catheterization. CONCLUSION: Retroperitoneal hematomas in patients with altered hemostasis and femoral vessel catheterization do not show a unique distribution attributable solely to contiguous spread of blood from the vessel puncture site. Many of these hematomas probably arise at sites distant from the femoral vessel puncture. When the hematoma is not contiguous with the punctured femoral vessels, altered hemostasis is most likely the cause of the hemorrhage. PMID- 8456682 TI - Arterial complications from long-term hepatic artery chemoinfusion catheters: evaluation with CT. AB - OBJECTIVE: The purpose of this study was to define CT changes in the common hepatic artery and the porta hepatis caused by complications of long-term placement of a catheter in the hepatic artery for infusion of chemotherapeutic agents via a surgically implanted pump or port. MATERIALS AND METHODS: We retrospectively reviewed abdominal CT scans of 115 patients before and after placement of a catheter into a hepatic artery for chemoinfusion, with special attention to the common hepatic artery and the porta hepatis. The changes seen on CT scans were correlated with clinical findings and other imaging findings (arteriography and radionuclide scanning) in patients who had symptoms related to catheters and pumps, including pain during treatment, persistent pain without apparent cause, or occlusion of the catheter. RESULTS: CT scans of 20 patients (17%) showed changes along the common hepatic artery. Five had rounded, low density fluid collections around the tip of the catheter, believed to be caused by extravasation of chemotherapeutic agents or heparin. Five had well-defined soft-tissue densities along the hepatic artery, where the tip of the catheter was located; these were thought to be caused by dissection of the artery with periarterial fibrosis. Ten had poorly defined areas of low density along the vessel, which may have been caused by periarterial edema, arteritis, or extravasation of the chemotherapeutic agents. Two patients had pain on injection through the device, but no changes were seen on CT scans. Fourteen of 16 patients who had symptoms related to infusion catheters had CT changes in the porta hepatis. CONCLUSION: Fluid collections and soft-tissue densities around the tip of the catheter and along the hepatic artery seen on CT scans of patients who had surgical placement of catheters for chemoinfusion should be recognized as possible complications from the treatment and lead to further study to confirm the diagnosis. PMID- 8456683 TI - Misperfusion of the liver during hepatic artery infusion chemotherapy: value of preoperative angiography and postoperative pump scintigraphy. AB - OBJECTIVE: One purpose of this study was to determine if patients who have anatomic variations in their hepatic arteries are at increased risk for complications associated with the use of intrahepatic arterial infusion pumps. We also tried to determine the value of perfusion studies obtained with 99mTc microspheres or 99mTc-macroaggregated albumin in detecting postoperative hepatic or visceral misperfusion and in predicting complications in patients with anatomic variants despite pre- or intraoperative attempts to correct the arterial abnormality. SUBJECTS AND METHODS: We prospectively compared findings on scintigrams obtained after delivering the radionuclide through intrahepatic arterial infusion pumps with anatomic variations in hepatic arteries seen on celiac and superior mesenteric hepatic arteriograms obtained before placement of the pump in 49 consecutive patients with colon carcinoma metastatic to the liver. RESULTS: Despite pre- or intraoperative attempts to correct arterial abnormalities to ensure optimal perfusion of the liver in 24 patients with hepatic arterial anomalies seen on preoperative arteriograms, only two patients had normal findings on postoperative perfusion studies performed with 99mTc microspheres and/or 99mTc-macroaggregated albumin. Abnormalities included perfusion of extrahepatic organs, including the spleen in 12 patients, stomach in seven, bowel in four, and pancreas in three. Eight patients had no perfusion of the left lobe of the liver, and three had no perfusion of the right lobe. Two patients had minimal or no perfusion of both lobes. In 23 of 25 patients with no demonstrable variations in vascular anatomy on preoperative celiac and superior mesenteric arteriograms, findings on hepatic pump scintigrams were normal. Of the 24 patients with abnormal scintigraphic findings, 20 had subsequent clinical complications. However, only two of the 25 patients with normal scintigraphic findings had clinical complications. CONCLUSION: Our results indicate that patients with anatomic variations in the hepatic arterial system are at high risk for misperfusion during chemotherapy despite pre- or intraoperative efforts to alter the perfusion for chemotherapeutic agents delivered by intrahepatic arterial infusion pumps. Misperfusion can be detected by using pump scintigraphy, and therefore patients should be closely monitored with 99mTc-macroaggregated albumin perfusion studies to ensure successful delivery of the chemotherapeutic agents and to avoid serious clinical complications caused by inadvertent perfusion of other organs. PMID- 8456684 TI - Percutaneous cholecystostomy for acute acalculous cholecystitis in a critically ill patient. PMID- 8456685 TI - MR imaging of a patient with a ferromagnetic foreign body. PMID- 8456686 TI - Mediastinal lymphadenopathy and Mycoplasma pneumoniae: an atypical presentation? PMID- 8456687 TI - Noninvasive thymoma in a 15-year-old girl: CT findings. PMID- 8456688 TI - CT demonstration of an intrathoracic rib. PMID- 8456689 TI - Pilomatrixoma mimicking male breast carcinoma on mammography. PMID- 8456690 TI - Intraluminal duodenal diverticulum: radiologic and CT findings. PMID- 8456691 TI - Xylocaine plus methylene blue vs methylene blue alone for marking breast tissue preoperatively. PMID- 8456692 TI - Anastomotic failure after gastrectomy mimicking recurrent tumor. PMID- 8456693 TI - Deformity associated with use of a gastrostomy tube: CT findings. PMID- 8456694 TI - Angiodysplasia of the colon mimicking adenocarcinoma. PMID- 8456695 TI - Nocardia brasiliensis liver abscesses in an AIDS patient: imaging findings. PMID- 8456696 TI - Massive biloma in lesser sac of peritoneal cavity after cholecystectomy. PMID- 8456697 TI - Contrast-enhanced MR imaging of idiopathic hypertrophic craniospinal pachymeningitis. PMID- 8456698 TI - Balo's concentric sclerosis: a rare form of multiple sclerosis manifested as a dominant cerebral mass without other white matter lesions on MR. PMID- 8456699 TI - MR of human postmortem brain tissue: correlative study between T2 and assays of iron and ferritin in Parkinson and Huntington disease. AB - PURPOSE: To test the hypothesis that the T2 shortening observed on MR images of the brain in patients with Parkinson and Huntington diseases is due to tissue iron deposition. METHODS: Tissue iron and ferritin assays were performed on postmortem putamen and globus pallidus samples from subjects with Huntington and Parkinson disease. The assays were correlated with T2 measurements. Normal samples were included as controls. RESULTS: There were significant differences in T2 values, and iron and ferritin concentrations among the putamen samples. Compared with normal controls, subjects with Huntington disease had approximately a threefold increase in iron and a sixfold increase in ferritin concentrations; however, they also had the longest T2 values. Parkinson disease putamens had milder elevations of iron concentrations above that of controls (33%) and demonstrated slightly shorter T2 values. The globus pallidus samples demonstrated a similar trend in their T2s, iron, and ferritin levels, but there was a larger overlap in the T2 values. CONCLUSIONS: Our results indicate that tissue iron and ferritin concentrations are elevated in the brains of subjects with both Parkinson and Huntington disease but the elevated concentrations do not correlate with T2 shortening. Although iron and ferritin can shorten T2, we conclude that other factors must play a significant role in determining the T2 relaxation time and that iron or ferritin are not dominant in this regard. PMID- 8456700 TI - Historical vignette: introduction of computed tomography in North America. PMID- 8456701 TI - Cerebrovascular transit characteristics of DyDTPA-BMA and GdDTPA-BMA on normal and ischemic cat brain. AB - PURPOSE: To compare the efficacy of two nonionic T2*-shortening contrast agents, DyDTPA-BMA dysprodiamide injection and GdDTPA-BMA gadodiamide injection, as perfusion-sensitive MR imaging agents in normal and acutely ischemic brain. METHODS: The magnetic susceptibility effects of intravenous injections of 0.10 0.50 mmol/kg of each contrast agent were quantified on T2-weighted spin-echo images of cat brain before and after unilateral occlusion of the middle cerebral artery by measuring signal intensity changes in the same regions-of-interest in parietal cortex. RESULTS: In normal brain, DyDTPA-BMA produced a significantly greater loss of signal intensity than equimolar doses of GdDTPA-BMA. The magnitude of the signal intensity attenuation was dosage-dependent and proportional to the square of the magnetic moments of the two contrast agents. Restoration of baseline image signal intensity was observed within 30 min after each injection. However, injection of GdDTPA-BMA also produced a delayed, persistent hyperintensity on T2-weighted images, presumably due to its underlying T1-shortening effect. Following unilateral occlusion of the middle cerebral artery, unenhanced T2-weighted images failed to show evidence of cerebral injury for 1.5-3 hours. Administration of 0.10-1.0 mmol/kg DyDTPA-BMA shortened the time for detection of perfusion deficits (residual hyperintensity) in 22 of 36 (61%) treated cats, often to within 30 min after arterial occlusion. DyDTPA-BMA enhancement also improved lesion conspicuity in 26 of 36 (72%) cases, and disclosed very small infarcts that were not visible on T2-weighted precontrast images. Perfusion deficits in areas of partial ischemia were seen more clearly on DyDTPA-BMA-enhanced images than after equimolar injections of GdDTPA-BMA. CONCLUSIONS: Magnetic susceptibility contrast-enhanced MR imaging enables detection of perfusion deficits associated with acute cerebral ischemia well in advance of conventional T2-weighted spin-echo MR imaging without contrast. DyDTPA BMA appears to delineate regions of ischemic damage better than GdDTPA-BMA. PMID- 8456702 TI - Endovascular treatment of cerebral arteriovenous malformations following radiosurgery. AB - PURPOSE: Previous reports of embolization of cerebral arteriovenous malformations (AVMs) have evaluated the technique as adjunctive therapy prior to surgery or radiosurgery; our aim is to assess the role of embolization following radiosurgery. PATIENTS: Six patients previously treated with radiosurgery and showing no response as judged by cerebral angiography were embolized 24 to 55 months (mean 34.3 months) after initial radiosurgery. RESULTS: In five of six, a significant volume reduction was achieved ranging from 60%-100% (mean 74%). One patient was treated with embolization alone and the AVM has remained fully thrombosed 2 years after treatment. Three patients underwent surgical resection for cure after embolization, and two patients had repeat radiosurgery to a significantly smaller AVM volume. One patient had an asymptomatic carotid dissection at embolization; however, no clinically apparent complications occurred in the treatment group. CONCLUSION: Embolization can be used after radiosurgery to assist in the management of those AVMs that have not responded to initial treatment. PMID- 8456703 TI - Hemangiomas and vascular malformations of the head and neck: MR characterization. AB - PURPOSE: To characterize the MR appearance of the common hemangioma of infancy as well as low- and high-flow vascular malformations of the head and neck. PATIENTS AND METHODS: Twenty patients with vascular lesions of the head and neck proved either by pathology, angiography, and/or unequivocal clinical diagnosis were included. Vascular lesions included 15 low-flow lesions (four hemangiomas, 10 venous malformations, one lymphatic malformation), and five high-flow lesions (three arteriovenous malformations (AVMs) and two invasive combined malformations). All patients had MR studies (generally 1.5 T using routine T1- and T2-weighted spin-echo sequences). Nine had postgadolinium, gradient recalled echo, CT, and/or angiographic studies. FINDINGS: Deep hemangiomas and venous malformations demonstrate intermediate signal in T1-weighted images, heterogeneous high signal on T2-weighted images, and prominent enhancement. Involuting hemangiomas show focal areas of high signal intensity on T1-weighted images due to fatty replacement. Venous malformations may demonstrate venous lakes seen as homogeneous regions of high signal intensity on T2-weighted images and phleboliths seen as low signal foci. The one patient with lymphatic malformation showed a large multicystic submandibular mass with large hemorrhage fluid levels. Features of high-flow lesions (AVMs) include serpiginous signal voids, absence of a dominant mass, and intraosseous extension with decreased marrow signal on T1-weighted images. Invasive combined vascular malformations showed serpiginous flow voids and infiltrative solid masses. Low-flow lesions (hemangiomas, venous, and lymphatic malformations) demonstrate distinct MR findings allowing their differentiation from high-flow lesions (AVMs). Deep hemangiomas and venous malformations appear as solid masses and may look identical. Venous lakes and phleboliths are features of venous malformations which, when present, may help in diagnosis. Combined vascular malformations share features of both low- and high-flow malformations. CONCLUSION: MR is useful in delineating the extent of disease and differentiating low- and high-flow vascular lesions. PMID- 8456704 TI - Pseudoaneurysms within ruptured intracranial arteriovenous malformations: diagnosis and early endovascular management. AB - PURPOSE: To draw attention to pseudoaneurysms within ruptured arteriovenous malformations and to consider their diagnostic and therapeutic features, including pitfalls and precautions needed for safe embolization. METHODS: Radiologic and clinical charts of 189 patients who bled from intracranial arteriovenous malformations were retrospectively reviewed. RESULTS: Fifteen of the 189 (8%) were found to have pseudoaneurysms. Nine of the pseudoaneurysms were arterial, six were venous. In the early period following hemorrhage, nine patients were treated conservatively. The other six were treated with surgery (one case) or embolization (five cases) because urgent intervention was required. The clinical outcome for both conservative and interventional groups was generally favorable, but one patient in the conservative group died of a rebleed. In the patients who underwent embolization, the fragile nature of the pseudoaneurysm made it necessary to first embolize the artery feeding it. Embolization with particles was considered hazardous. Instead, free-flow (nonwedged) N-butyl-cyanoacrylate embolization proved safe and effective in treating both the pseudoaneurysms and arteriovenous malformations in these cases. CONCLUSIONS: This study highlights the importance of recognizing pseudoaneurysms in such patients and the importance of using free-flow liquid adhesive material on the artery feeding the pseudoaneurysm if embolization is required. PMID- 8456705 TI - Endovascular packing of carotid bifurcation aneurysm with polyester fiber-coated platinum coils in a rabbit model. AB - PURPOSE: To assess the value of endovascular packing of intracranial bifurcation aneurysms with commercially available coils. METHODS: Carotid bifurcation aneurysms were surgically created in 12 New Zealand rabbits with subsequent assessment of the extent of aneurysm ablation following endovascular packing with polyester fiber-coated platinum coils. RESULTS: Follow-up angiograms obtained from 29 to 108 days postprocedures showed various degrees of aneurysm ablation. Complete obliteration of aneurysm dome occurred in seven out of eight rabbits, while ablation of aneurysm neck was successful in only one out of eight. No spontaneous thrombosis was observed in seven control animals over a 3-month period. Coils of various configurations used in this experiment all maintained stable intraaneurysmal position. Histologic examination of treated aneurysms consistently demonstrated extensive proliferation of spindle cells on the coil surface and in interstices between coils with channels lined by cells resembling endothelial cells. Organized thrombus was not a prominent feature. CONCLUSION: Endovascular packing of human bifurcation aneurysms with current commercially available polyester fiber-coated platinum coils may not result in complete obliteration of the aneurysm with reendothelialization occurring across the aneurysm neck. PMID- 8456706 TI - Treatment of a spontaneous carotid cavernous fistula using an electrodetachable microcoil. AB - The authors detail their use of a modified version of an electrolysis coil currently manufactured in the United States. They connect a platinum wire to a stainless steel wire via a copper segment, and apply low voltage current to induce thrombosis while electrolysis of the copper effects separation of the platinum coil. Their technique shows potential for treatment of complicated carotid cavernous fistulas. PMID- 8456707 TI - Nondissecting vertebral fusiform aneurysm: embolization using wire-directed detachable balloons. AB - The authors report the embolization of an unruptured nondissecting vertebral fusiform aneurysm using a new silicone detachable balloon that they have developed, which is advanced without inflation over a guide wire. PMID- 8456708 TI - Superselective embolization for severe traumatic epistaxis caused by fracture of the skull base. AB - Intractable epistaxis developed in a 13-year-old girl after she fell down a flight of stairs sustaining facial fractures and fracture of the skull base. Epistaxis was found to emanate from a right ascending pharyngeal artery, which the authors promptly and successfully embolized using polyvinyl alcohol particles and microfibrillar collagen. PMID- 8456710 TI - Limbic system anatomy: an overview. PMID- 8456709 TI - Intraarterial papaverine as an adjunct to transluminal angioplasty for vasospasm induced by subarachnoid hemorrhage. AB - Basilar artery vasospasm refractory to medical therapy was confirmed by clinical deterioration and angiography in a 47-year-old man; successful passage of a nondetachable balloon system and angioplasty were facilitated by intraarterial papaverine. PMID- 8456711 TI - Scalloping deformity of the corpus callosum following ventricular shunting. AB - PURPOSE: To describe six patients who underwent ventriculoperitoneal (V-P) shunting for hydrocephalus and developed scalloping deformity of the dorsal surface of the corpus callosum, and to evaluate the cause and frequency of this phenomenon. MATERIALS AND METHODS: MR images of 35 patients whose hydrocephalus was successfully corrected by V-P shunting were studied. To elucidate the possible anatomic basis for the scalloping deformity, gross examination of the corpus callosum relative to the adjacent anatomical structures was performed using autopsy specimens. RESULTS: Of the 35 patients who underwent successful V-P shunting, six (17%) developed a scalloping deformity of the corpus callosum. The deformity was noted exclusively in the body of the corpus callosum. This phenomenon was observed in both obstructive and communicating hydrocephalus regardless of the patient's age, but was particularly noted in patients with tectal tumors. CONCLUSION: The cause of this phenomenon may be a combination of long-standing hydrocephalus and normal pericallosal artery anatomy. Prolonged hydrocephalus softens the corpus callosum and the branches of the pericallosal arteries tether the corpus callosum to the overlying cingulate cortex at periodic intervals. PMID- 8456713 TI - Spinal epidural hematoma with subarachnoid hemorrhage caused by acupuncture. AB - Unintentional acupuncture needling of the thoracic spinal canal produced a spinal epidural hematoma and subarachnoid hemorrhage. This case demonstrates that patients are sometimes reluctant to disclose folk medical treatments to Western physicians, and the proper diagnosis may depend upon the prowess of the neuroradiologist. PMID- 8456712 TI - MR appearance of extravasated gadolinium contrast medium. AB - This case illustrates that a large zone of signal void can be produced on short relaxation time MR images when gadopentate dimeglumine is injected through an infiltrated intravenous catheter. The authors consider the physics behind this paradoxical decrease in signal intensity where there are high concentrations of gadopentate dimeglumine. PMID- 8456714 TI - Odontogenic cysts: improved imaging with a dental CT software program. AB - PURPOSE: To evaluate a dental CT software program to determine whether it can provide a better means of assessing odontogenic cysts, lesions of the jaw derived from dental epithelium, than conventional techniques (orthopantomographic, intraoral, and mandibular films), which are of limited usefulness because of the curved configuration of the mandible; and to provide a brief review of these lesions. METHODS: Nine odontogenic cysts were studied with conventional radiographs and with the software program, which displays multiple cross referenced axial, panoramic, and cross-sectional (unique to this program) views of the mandible. The two modalities were compared for delineation of anatomy (inferior alveolar canal, mandibular foramen, mental foramen), detection of neurovascular bundle displacement, detection of cortical bone involvement, and detection of root involvement. RESULTS: The software program rated higher regarding all four points. It was found to be superior for delineating anatomy and detecting mandibular canal displacement and cortical and root involvement. CONCLUSIONS: This software program should be the study of choice when evaluating odontogenic cysts and other lesions of the mandible. PMID- 8456715 TI - The added gradient echo pulse sequence technique: application to imaging of fluid in the temporomandibular joint. AB - PURPOSE: To assess the value of an added gradient echo in the same pulse sequence with a T1-weighted spin echo for determining the presence of an abnormal fluid collection in the temporomandibular joint with no additional imaging time. MATERIALS AND METHODS: Using a standard T1-weighted sequence used in cine temporomandibular joint imaging, a readout gradient reversal was added and the resulting gradient echo collected. This image was compared with standard T1- and T2-weighted sequences, a short inversion recovery imaging sequence, and a small flip angle fast low-angle shot gradient-echo sequence. RESULTS: The T1-weighted spin echo preceding the added gradient echo is not affected by the gradient reversal, but the additional gradient echo adds T2* contrast information that displays fluid as bright as and compares favorably with other fluid detection sequences. CONCLUSION: The added gradient-echo technique adds sensitivity for the detection of an abnormal increase in fluid in the temporomandibular joint without adding to the overall imaging time of a routine T1-weighted sequence. PMID- 8456716 TI - Spinal nerve enhancement with Gd-DTPA: MR correlation with the postoperative lumbosacral spine. AB - PURPOSE: To search for a probable source of the recurrent signs and symptoms associated with lumbosacral postsurgical syndrome on intravenous gadolinium enhanced MR. METHODS: A retrospective study of 120 patients with recurrent symptomatology following lumbar disk surgery was carried out with spin-echo MR pre- and postenhancement with gadopentetate dimeglumine (0.1 mmol/kg). In addition, 10 asymptomatic subjects were evaluated at least 6 months postoperatively using the same imaging protocol. RESULTS: 21.6% of the symptomatic subjects (N = 26) had enhancement of one or more spinal nerve root. This enhancement was focal or multisegmental, and involved single or multiple nerve roots. The abnormal neural enhancement was associated with otherwise isolated epidural fibrosis in 88.5%, and with herniated nucleus pulposus in the remaining 11.5%. The overall clinical correlation of single root enhancement with a monoradiculopathy and multiroot enhancement with a polyradiculopathy was 95.7%. However, 21.7% of these same cases also showed additional nerve root enhancement that did not have an overt clinical correlation. All of these latter patients were imaged relatively early in the postoperative period (5 days to 8 months). The 10 patients in the asymptomatic group all manifested degrees of postoperative epidural scarring on MR, but no abnormal radicular enhancement or other associated pathology. CONCLUSION: In the chronic postoperative phase (more than 6 to 8 months), the presence of radicular enhancement on MR imaging in symptomatic individuals, and its absence in asymptomatic subjects, suggests that neural enhancement serves as a marker for active neural pathology that may in certain individuals be related temporally to the signs and symptoms associated with the lumbosacral postsurgical syndrome. PMID- 8456717 TI - Migration of luque rods through a laminectomy defect causing spinal cord compression. AB - Internal fixation of traumatic spinal injuries has been associated with spinal canal stenosis, spinal cord compression, and nerve root impingement. We present a case of spinal cord/cauda equina compression due to migration of intact, anchored thoracolumbar Luque rods into the spinal canal through a laminectomy defect, leading to neurologic complications 10 years after the original operation. PMID- 8456718 TI - Ependymoma of the cauda equina presenting with subarachnoid hemorrhage. AB - A 16-year-old girl had an ependymoma at the L2 and L3 level that bled into the dural sac, presenting clinically as intracranial subarachnoid hemorrhage. MR depicted the tumor and hemorrhage on both T1- and T2*-weighted images. The blood in the dural sac appeared hyperintense on the T1-weighted images. PMID- 8456719 TI - Intradural lumbar disk fragment with ring enhancement on MR. AB - Intradural extension of a herniated intervertebral disk, an unusual complication of a common disease, may mimic an intradural tumor on MR. A case of a pathologically proved subdural disk fragment is presented; MR findings that suggested the correct diagnosis were: proximity of intervertebral disk disease; whorl-like mixed intensity on T2-weighted images; poor visualization of the mass on unenhanced T1-weighted images; and marked ring enhancement following administration of gadolinium. PMID- 8456720 TI - Association of linear sebaceous nevus syndrome and unilateral megalencephaly. AB - We report unilateral megalencephaly in a 14-year-old girl with linear sebaceous nevus syndrome. A review of the radiologic findings in this case and in previously reported cases suggests that the seizures and developmental delay in this neurocutaneous syndrome are related to the migration anomaly of unilateral megalencephaly. PMID- 8456721 TI - Sturge-Weber syndrome: cranial MR imaging with Gd-DTPA. AB - PURPOSE: To study the role of Gd-DTPA in cranial MR of patients with Sturge-Weber syndrome. METHODS AND MATERIALS: Seven patients with Sturge-Weber syndrome, ages 3 months to 36 years, were evaluated with unenhanced and contrast-enhanced (Gd DTPA) MR imaging. Correlation was made to cranial CT in five patients. RESULTS: MR findings included (in decreasing frequency): pial angiomatosis, cerebral atrophy, decrease in cortical veins, enlargement of deep veins, enlargement of choroid plexus, and parenchymal calcification. Contrast MR imaging was essential in diagnosis in four cases in which cranial CT, unenhanced MR, or angiography was normal or demonstrated nonspecific abnormalities. Pial angiomatosis with adjacent cerebral atrophy were the only consistent radiographic abnormalities. CONCLUSION: In all patients, contrast MR demonstrated the radiographic spectrum of central nervous system abnormalities in Sturge-Weber syndrome to a greater degree than unenhanced MR or CT and may represent the method of diagnosis in these patients. Demonstration of the pial angioma on contrast MR should be considered the most important criterion for the radiographic diagnosis of Sturge-Weber syndrome. PMID- 8456722 TI - MR and MR angiography of Sturge-Weber syndrome. AB - PURPOSE: To assess the potential of magnetic resonance angiography (MRA) as an adjunct to spin-echo sequences in evaluating the cerebral vascular anomalies seen in Sturge-Weber syndrome. METHODS: Four pediatric patients with Sturge-Weber syndrome were evaluated with conventional MR imaging and with arterial and venous MRA. Resultant images were evaluated for evidence of volume loss, cortical enhancement, vascular anomalies, and enlarged choroid plexus. RESULTS: Venous MRA revealed reduced flow of the transverse sinuses and jugular veins, prominent deep collateral venous system, and a lack of superficial cortical veins. Arterial MRA, performed in all cases, revealed a reduced flow signal from the left middle cerebral artery in one hemiparetic patient and angiomatous changes of high branches of a middle cerebral artery in two patients. CONCLUSION: Arterial and, in particular, venous MRA can be useful adjuncts to standard spin-echo sequences in diagnosing Sturge-Weber syndrome. PMID- 8456723 TI - Proton MR spectroscopic characteristics of a presumed giant subcortical heterotopia. AB - A newborn presented with a mass replacing the left cerebral hemisphere. Although the internal signal characteristics of the lesion were suggestive of disorganized gray and white matter, a true neoplasia such as a ganglioglioma could not be totally excluded. Biopsy is not recommended in these cases since the results may be misleading. Proton MR spectroscopy was used; this technique also suggested the hamartomatous nature of the lesion. Based on the clinical course and the imaging features, conservative therapy and observation were undertaken instead of surgery. At 6 months of age, the patient is stable and the lesion is unchanged. PMID- 8456724 TI - Middle interhemispheric fusion: an unusual variant of holoprosencephaly. AB - PURPOSE: To describe the imaging features of a brain anomaly found on studies of three patients, and to speculate on the embryologic basis leading to the development of this abnormality. PATIENTS AND METHODS: Clinical records (three patients), MR scans (two patients), and CT scans (two patients) of three patients with fusion of the middle portions of the cerebral hemispheres in the presence of nearly normal anterior interhemispheric fissures were retrospectively reviewed. The results were correlated with the present theories of brain development in an attempt to classify the anomaly and define the underlying embryologic abnormalities. RESULTS: All three patients with middle interhemispheric fusion were severely developmentally delayed. Associated anomalies were identified in all three and included neuronal migration anomalies, callosal dysgenesis, and hypoplasia of the anterior falx cerebri. Correlation of the imaging findings with theories of brain development lead to the suggestion that this anomaly is the result of deficient or dysplastic mesenchyme, which leads to disordered brain development. CONCLUSION: Middle interhemispheric fusion may be considered as a variant of holoprosencephaly. It is suggested that the mesenchyme formed by the prechordal plate, notochord, and neural crest play an important part in the early development of the brain and that anomalies of the mesenchyme underlie this disorder as well as other forms of holoprosencephaly. PMID- 8456725 TI - MRA detection of vascular occlusion in a child with progeria. AB - We report a case of progeria and the utility of visualizing the cerebrovascular anatomy by using MR angiography. A 4-year-old child with Hutchinson-Guilford syndrome developed symptoms of ischemia and MR angiography showed bilateral occlusion of internal carotid and vertebral artery origins; the anterior spinal artery was prominent. PMID- 8456726 TI - Postinfectious encephalopathy in a child following Campylobacter jejuni enteritis. AB - We report a case of acute postinfectious encephalopathy in a child following Campylobacter jejuni enteritis. Serial MR scans showed lesions involving predominantly gray matter and the adjacent subcortical white matter--findings different from those in other immune-mediated disorders, such as systemic lupus erythematosus, in which either white or gray matter may be involved, and acute disseminated encephalomyelitis, in which white matter abnormalities predominate with involvement of the subcortical white matter. PMID- 8456727 TI - MR findings in oculocerebrorenal syndrome. AB - Oculocerebrorenal syndrome is an X-linked recessive disorder characterized by congenital ocular abnormalities, mental retardation, renal disease, and metabolic bone disease. We report a case of oculocerebrorenal syndrome and, using T1-, proton density-, and T2-weighted imaging sequences, are able to characterize two distinct white matter abnormalities: one lesion is punctate and has signal characteristics that parallel that of cerebrospinal fluid; a second lesion, found in association with the first, consists of patchy white matter abnormalities that are hypointense on T1-weighted images but hyperintense on proton density- and T2 weighted images. PMID- 8456728 TI - Chondrosarcoma of the larynx: CT features. AB - PURPOSE: To define the typical CT features of chondrosarcoma of the larynx. PATIENTS AND METHODS: Results of CT studies, performed on 10 patients with pathologically proved chondrosarcoma of the larynx, were retrospectively reviewed and correlated with clinical presentation. RESULTS: In all patients, the mass was detected on CT. The most frequent site of origin of the tumor was the cricoid cartilage (nine cases) followed by the thyroid cartilage (one case). Coarse or stippled calcification within the tumor was the most helpful radiologic finding and was seen in every case. In eight patients, the tumor had both an endolaryngeal and an extralaryngeal growth pattern, whereas in two patients the tumor was entirely endolaryngeal. Hoarseness, dyspnea, and dysphagia were the most common symptoms. In all patients presenting with dyspnea, the tumor exhibited endolaryngeal components. In patients presenting with hoarseness, three tumors had endolaryngeal and extralaryngeal components and two tumors were entirely endolaryngeal. CONCLUSION: Cross-sectional imaging afforded excellent evaluation of the airway as well as the extralaryngeal component of the tumor. PMID- 8456729 TI - Levator scapulae muscle asymmetry presenting as a palpable neck mass: CT evaluation. AB - PURPOSE: To define the normal CT anatomy of the levator scapulae muscle and to report on a series of five patients who presented with a palpable mass in the posterior triangle due to asymmetry of the levator scapulae muscles. PATIENTS AND METHODS: The contrast-enhanced CT examinations of the neck in 25 patients without palpable masses were reviewed to establish the normal CT appearance of the levator scapulae muscle. We retrospectively reviewed the contrast-enhanced CT examinations of the neck in five patients who presented with a palpable mass secondary to asymmetric levator scapulae muscles. RESULTS: In three patients who had undergone unilateral radical neck dissection, hypertrophy of the ipsilateral levator scapulae muscle was found. In one patient, the normal levator scapulae muscle produced a factitious "mass" due to atrophy of the contralateral levator scapulae muscle. One patient had an intramuscular neoplasm of the levator scapulae. CONCLUSION: Asymmetry of the levator scapulae muscles, an unusual cause of a posterior triangle mass, can be diagnosed using CT. PMID- 8456731 TI - MR appearance of an orbital leiomyoma. AB - The authors describe the MR appearance of an intraconal orbital vascular leiomyoma that probably arose from smooth muscle in the wall of a vein. Cavernous hemangiomas, schwannomas, neurofibromas, and other well-encapsulated masses can have a similar appearance. PMID- 8456730 TI - The extracranial facial nerve: high resolution three-dimensional Fourier transform MR imaging. AB - PURPOSE: To investigate the use of high-resolution three-dimensional Fourier transform gradient-echo MR in evaluation of the extracranial facial nerve. METHODS: Nine normal subjects and one clinical patient were scanned. Several imaging parameters, including echo time, field-of-view, and the use of Gd-DTPA, were manipulated to determine the optimal technique. Adequate results were obtained in less than 7 minutes acquisition time using a T1-weighted (50/5.3) gradient-echo technique, with a 30 degree flip angle, a 12-cm field of view, 128 x 256 matrix, and 28 or 60 1.0-mm-thick contiguous sections. RESULTS: Gd-DTPA administration was not found useful in identifying the normal extracranial facial nerve. The proximal extracranial facial nerve was seen as a branching low signal intensity tubular structure on 10 to 20 contiguous images in all five volunteers in which this optimal technique was employed. Postprocessing of the images to produce curved oblique planar reconstructed images was useful to display long segments of the facial nerve on a single image. CONCLUSION: Our experience with high resolution three-dimensional Fourier transform MR imaging indicates that it can consistently demonstrate the intraparotid facial nerve on multiple contiguous images. PMID- 8456732 TI - Hyperventilation-induced cerebral ischemia in patients with acute brain lesions: demonstration by xenon-enhanced CT. AB - PURPOSE: To examine the possibility that hyperventilation, commonly used to prevent or treat increased intracranial pressure in patients with acute brain lesions, may induce significant cerebral ischemia. METHODS: Local cerebral blood flow and vascular reactivity were measured before and after hyperventilation using xenon-enhanced CT in 12 patients with acute brain lesions. RESULTS: Five patients showed "paradoxical" reactivity (increased cerebral blood flow during hyperventilation) within the lesions. In five patients, hyperventilation induced ischemia in apparently normal regions of brain. In three patients, areas of luxury perfusion became ischemic during hyperventilation, while in three patients, lesions with moderate ischemia became more ischemic. Most patients showed more than one type of reactivity. CONCLUSIONS: These findings document hyperventilation-induced ischemia in acute brain lesions, and demonstrate that this phenomenon affects both injured and apparently intact areas of the brain. Further studies are required to determine the clinical significance of these pathophysiologic changes. PMID- 8456733 TI - Bilateral subclavian steal: a review of an unusual twist in a common disorder. AB - The authors present two cases of bilateral subclavian steal syndrome, a rare condition that does not commonly cause neurovascular symptoms. Lateralizing hemispheric events occur usually with carotid lesions. Vertebral-basilar insufficiency is three times more common in bilateral than in unilateral subclavian steal syndrome. Arm-exercise-induced brain-stem dysfunction is rare, and is seen only in bilateral subclavian steal syndrome. PMID- 8456734 TI - Thrombotic thrombocytopenic purpura: MR findings. AB - Neurologic manifestations occur in over 90% of patients with thrombotic thrombocytopenic purpura. Neuropathologically, thrombi produce occlusion of terminal arterioles and capillaries resulting in diffuse small infarcts. In the great majority of surviving patients, brain CT does not disclose any abnormalities. The authors report a case of thrombotic thrombocytopenic purpura in which brain MR examination showed multiple punctate lesions in the white matter. PMID- 8456735 TI - Intraventricular fibroma: MR and pathologic comparison. AB - This case report describes clinical, surgical, MR, and pathologic findings of an intraventricular fibroma, a rare, benign mesenchymal neoplasm. Relatively isointense with normal brain parenchyma on T1-weighted images, the tumor exhibited hyperintense signal on T2-weighted pulse sequences and enhanced intensely and homogeneously after intravenous administration of gadopentetate dimeglumine. Choroid plexus papilloma/carcinoma, meningioma, ependymoma, and subependymal giant cell astrocytoma should be included in the differential diagnosis. PMID- 8456736 TI - CNS complications in acute malaria: MR findings. AB - MR showed a small, acute hemorrhage adjacent to an area of infarction in the parieto-occipital lobe in a man with acute malaria. PMID- 8456737 TI - Unusual location of a shunt tube in the basal subarachnoid space. AB - The authors observed flow-void in a shunt tube in the basal cisterns of a 28-year old man who had previously undergone surgery for a craniopharyngioma. They describe the appearance of a subarachnoid shunt catheter in the basal cisterns to caution against misinterpreting it as an aberrant vessel. PMID- 8456738 TI - Temperature changes in nickel-chromium intracranial depth electrodes during MR scanning. AB - The authors sought to determine whether there are any heating effects of 1.5-T MR scanning upon nickel-chromium electrodes and to confirm the safety of scanning these electrodes after intracranial surgical implantation in epilepsy patients. Since there was no significant temperature increase of the electrodes tested in their experiments, the authors conclude that nickel-chromium electrodes implanted in the brain are thermally safe for MR scanning. PMID- 8456739 TI - Annotated bibliography. PMID- 8456740 TI - Extradural hematomas: surgical and nonsurgical treatment. PMID- 8456741 TI - MR quantification of brain structures. PMID- 8456743 TI - CD-ROM software. PMID- 8456742 TI - Conclusions questioned. PMID- 8456744 TI - DUR programs: current trends and future directions. PMID- 8456745 TI - Pyrantel pamoate for pinworm infestation. PMID- 8456746 TI - Psychiatric promise: old drugs, new uses. PMID- 8456747 TI - Fluid losses with diarrhea. PMID- 8456748 TI - Revamping how pharmacists are paid. PMID- 8456749 TI - Messages about AIDS reach some, not all. PMID- 8456750 TI - Evaluation of the effectiveness of lipid-lowering therapy (bile acid sequestrants, niacin, psyllium and lovastatin) for treating hypercholesterolemia in veterans. AB - Veterans are frequently older, have more chronic illnesses, and take more medications than subjects volunteering for clinical trials. Because these factors may impair the effectiveness of lipid-lowering drug therapy, the effectiveness of drug therapy in veterans may differ from that measured in randomized controlled trials. In 297 patients with type IIa hyperlipidemia attending a large Veterans Administration Medical Center lipid clinic, adverse effects, compliance, lipid and lipoprotein responses to drug therapy were prospectively monitored. Bile acid sequestrants (4 packets/day) were associated with a high rate of adverse effects, and had the highest drug discontinuance rate (37%) and poorest compliance (73 +/- 3% of the doses prescribed reported ingested) of all agents. Patients aged > 60 years tolerated therapy with bile acid sequestrants less well than did younger veterans (p < 0.01). Niacin (1.5 g/day) also had a high drug discontinuance rate (27%). Lovastatin (20 mg/day) had the lowest drug discontinuance rate (2%) and the highest compliance (90 +/- 2%). Lovastatin also reduced low-density lipoprotein (LDL) cholesterol the most (-21.6 +/- 2.0%), whereas niacin produced the largest increase in high-density lipoprotein (HDL) cholesterol (+/- 14.3 +/- 2.2%); both niacin and lovastatin produced similar reductions in the LDL/HDL ratio. However, psyllium (10.4 g/day) reduced LDL cholesterol by only 2%, and had no effect on the LDL/HDL ratio. Psyllium produced larger LDL cholesterol reductions in patients aged < 60 years than in older patients (p < 0.01). Niacin and lovastatin are effective drugs for hypercholesterolemia management in the Veterans Administration Medical Center setting.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8456752 TI - Prognostic significance of transient myocardial ischemia on ambulatory monitoring after acute myocardial infarction. AB - The prognostic value of ambulatory ST-segment monitoring after myocardial infarction was prospectively assessed in 203 patients both early (mean 6 days, n = 201) and late (38 days, n = 177). During at least 1 year of follow-up there were 21 cardiac deaths and 44 cardiac events (death, reinfarction or coronary revascularization). ST depression was seen less often during early than late monitoring (29 of 201 [14%] vs 56 of 177 [32%]). Early ST depression was significantly associated with increased mortality (7 of 29 [24%] vs 14 of 172 [8%]) (< 0.05) and increased cardiac events (13 of 29 [45%] vs 30 of 172 [17%]) (p < 0.001) and had independent value after allowing for clinical factors and coronary prognostic indexes (adjusted relative risks 3.40 and 2.70, respectively). ST depression on late monitoring was only associated with increased cardiac events when it was: (1) frequent (e.g., > or = 3 episodes/day [10 of 31 patients, 32% vs 18 of 146, 12%]) (p < 0.01); (2) prolonged (e.g., > or = 20 minutes/day [8 of 25, 32% vs 20 of 152, 13%]) (p < 0.05); or (3) severe (e.g., maximum of > or = 1.5 mm [8 of 28, 29% vs 20 of 149, 13%]) (p < 0.05). Thus, ST depression occurs less frequently during ambulatory monitoring before discharge than during late monitoring, but is a more specific prognostic indicator; however, it is more benign during late monitoring. Ambulatory ST segment monitoring can be used to predict prognosis in the first year after myocardial infarction, although its relative value as a screening test compared with exercise testing remains to be established. PMID- 8456751 TI - Natural history of coronary atherosclerosis using quantitative angiography in men, and implications for clinical trials of coronary regression. The Harvard Atherosclerosis Reversibility Project Study Group. AB - Previous studies of the natural history of coronary disease generally relied on estimates of percent stenosis derived from visual assessment of the coronary angiogram. In a study of 26 patients, serial quantitative angiography was performed 3 years apart to determine changes in both absolute measurements of the luminal diameter and relative percent stenosis. Initially, the mean minimal diameter of 74 coronary obstructions was 1.94 +/- 0.09 mm, the mean "normal" reference diameter was 3.06 +/- 0.11 mm, and the mean percent stenosis was 37%. At follow-up, there was a mild reduction of 0.12 +/- 0.04 mm (6%) in the minimal diameter (p < 0.005), and an increase in percent stenosis to 39% (p = 0.03). The average diameter of 85 arterial segments without a focal obstruction either initially or at follow-up showed mild but significant progression (-0.11 +/- 0.04 mm; p = 0.02). Using a minimal change of 0.27 mm in arterial diameter as a categoric variable, progression occurred in 26% of 74 arterial segments, no significant change in 65%, and regression in 9%. The only significant determinant of disease progression was the initial severity of disease. Obstructed arteries with a larger initial minimal diameter and presumably milder disease progressed more rapidly than did those with a smaller diameter (r = -0.42; p = 0.0002). There was no effect of age on the rate of progression (r = 0.02; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8456753 TI - Anticoagulant effects of hirulog, a novel thrombin inhibitor, in patients with coronary artery disease. AB - Selective thrombin inhibitors are a new class of antithrombotic drugs that, unlike heparin, can effectively inhibit clot-bound thrombin and escape neutralization by activated platelets. Hirulog is a 20 amino acid hirudin-based synthetic peptide that has shown promise in experimental models of thrombosis. Little information is available about the effects of hirulog in patients with coronary artery disease. Forty-five patients undergoing cardiac catheterization, who were taking aspirin, were randomized to receive either (1) hirulog, 0.05 mg/kg intravenous bolus followed by 0.2 mg/kg/hour intravenous infusion until the end of the catheterization; (2) hirulog, 0.15 mg/kg intravenous bolus followed by 0.6 mg/kg/hour intravenous infusion; or (3) heparin; 5,000 U intravenous bolus. Serial activated partial thromboplastin time (APTT), prothrombin time, activated clotting time and fibrinopeptide A were measured. Hirulog produced a dose dependent prolongation of all coagulation parameters; the 0.6 mg/kg/hour dose prolonged the APTT to 218 +/- 50% of baseline after 2 minutes and 248 +/- 50% of baseline after 15 minutes. The half-life of the effect on APTT was 40 minutes. The hirulog blood level correlated well with the APTT, prothrombin time and activated clotting time (r = 0.77, 0.73, and 0.82 respectively, all p < 0.001). Both doses of hirulog potently suppressed the generation of fibrinopeptide A (p < 0.05). There were no major hemorrhagic, thrombotic or allergic complications in patients treated with hirulog or heparin. Thus, hirulog, a direct thrombin inhibitor, provides a predictable level of anticoagulation and appears to have a potent yet well-tolerated anticoagulant profile in patients with coronary artery disease. PMID- 8456754 TI - Minimizing the risk of inappropriately administering thrombolytic therapy (Thrombolysis and Angioplasty in Myocardial Infarction [TAMI] study group). AB - Despite the proven benefits of thrombolytic therapy in acute myocardial infarction, concern for its complications, especially in patients misdiagnosed with myocardial infarction, has led to hesitancy in its use. Historical, clinical and electrocardiographic criteria were developed for enrolling patients with suspected acute myocardial infarction into thrombolytic trials by noncardiovascular specialists. The incidence of misdiagnosis of myocardial infarction and the clinical outcomes when these criteria were used were evaluated for 1,387 consecutive patients given thrombolytic therapy. Twenty-five community hospitals and 7 interventional centers were the sites of enrollment. Most patients (63%) were enrolled from community hospitals. Criteria for thrombolytic therapy included: symptoms of acute myocardial infarction < 6 hours but > 20 minutes, and not relieved by nitroglycerin; and ST-segment elevation > or = 1 mm in 2 contiguous leads or ST-segment depression of posterior myocardial infarction. Exclusion criteria reflecting increased risk of bleeding were used. A final diagnosis of myocardial infarction was based on creatinine kinase-MB, electrocardiographic and ventriculographic evaluation. Acute myocardial infarction was misdiagnosed in 20 patients (1.4%; 95% confidence interval 0.8 2.0%). These patients were demographically similar to those with acute myocardial infarction. All misdiagnosed patients survived; no significant adverse events occurred. Thus, in several clinical settings, a simple algorithm with specific criteria was used for diagnosing acute myocardial infarction and administering thrombolytic therapy. The inclusion criteria used in this study led to a low rate of misdiagnosis. PMID- 8456755 TI - Effectiveness of thrombolysis is associated with a time-dependent increase of malondialdehyde in peripheral blood of patients with acute myocardial infarction. AB - By using a highly sensitive, high-performance liquid chromatographic technique, plasma values of malondialdehyde (MDA), adenosine and oxypurines were determined in 10 healthy subjects, 10 patients with noncardiac illness, and 20 patients with acute myocardial infarction (AMI) observed within 6 hours from the onset of symptoms. Patients with AMI received fibrinolytic treatment. Peripheral blood was obtained before and serially after thrombolysis (1, 2, 3, 6 and 24 hours). Coronary patency was assessed by timing of peak creatine phosphate kinase and by predischarge angiography. MDA (mean +/- SD) in healthy subjects, noncardiac patients, and immediately before thrombolytic treatment in patients with AMI was 0.051 +/- 0.013, 0.066 +/- 0.020 and 0.397 +/- 0.326 mumol/liter of plasma, respectively. A progressive increase in plasma MDA after thrombolysis was observed only in reperfused patients, whose values at the third, sixth and 24th hours were also significantly greater than those of nonreperfused patients. Time dependent variations of xanthine and adenosine were also observed in the same group after thrombolysis. The data appear to indicate that a relevant increase in plasma MDA, mostly originating due to phospholipid derangement of postischemic myocytes, occurs only in patients with successful thrombolysis, thus suggesting that if properly assayed, it may represent reliable biochemical evidence of tissue injuries after myocardial reperfusion in humans. PMID- 8456756 TI - Rotational coronary atherectomy after unsuccessful coronary balloon angioplasty. AB - The clinical and angiographic outcome of patients undergoing rotational coronary atherectomy after unsuccessful balloon angioplasty was evaluated using quantitative angiographic methods to provide insight into this procedure's mechanism of benefit. During the study period, 41 patients (50 lesions) were referred for rotational atherectomy after standard balloon angioplasty was unsuccessful. After rotational atherectomy, percent diameter stenosis was reduced from 72 +/- 14% to 41 +/- 16% (p < 0.001); adjunct balloon angioplasty was performed in 44 lesions (88%), resulting in a 25 +/- 17% final diameter stenosis (p < 0.001). The acute gain in minimal lumen diameter was 1.20 +/- 0.59 mm. In lesions needing adjunct balloon dilatation, lesion stretch was 73 +/- 27%, and elastic recoil was 22 +/- 18%, with no variation by etiology of the initial balloon failure. Overall angiographic success (< 50% residual diameter stenosis) was obtained in 49 lesions (98%). Procedural success, defined as < 50% residual diameter stenosis and the absence of major in-hospital complications (death, Q wave myocardial infarction or emergency bypass surgery), was obtained in 37 of 41 procedures (90%); complications developed in 3 patients (7%), including 2 who needed emergency bypass surgery after development of delayed abrupt closure. It is concluded that rotational coronary atherectomy may be used in selected patients when standard balloon angioplasty is unsuccessful. Its mechanism of benefit appears related, at least in part, to changes in plaque compliance resulting from partial atheroma ablation. PMID- 8456757 TI - Preliminary experience with adjunct directional coronary atherectomy after high speed rotational atherectomy in the treatment of calcific coronary artery disease. AB - A high-speed rotational atherectomy was performed followed by adjunct directional atherectomy in 10 patients with symptomatic coronary artery disease and calcified target lesions and the results were evaluated using quantitative coronary arteriography and intravascular ultrasound. Target lesion calcium is common in obstructive coronary artery disease. High-speed rotational coronary atherectomy preferentially abrades noncompliant atherosclerotic plaque material, especially calcium, but often requires adjunct balloon angioplasty to achieve optimal lumen dimensions. Directional coronary atherectomy has limited efficacy in heavily calcified plaque; usually, it is a definitive primary procedure in large arteries with noncalcified target lesions. Neither of these devices alone is effective in treating calcified target lesions in large coronary arteries. Before intervention, after rotational and adjunct directional atherectomy, these measurements were obtained: quantitative coronary arteriographic measurements of minimal lumen diameter and percent diameter stenosis and intravascular ultrasound measurements of external elastic membrane, lumen, and plaque+media cross sectional areas; percent cross-sectional narrowing; minimal lumen diameter; and target-lesion arc of calcium. With use of quantitative coronary arteriography, the preintervention minimal lumen diameter measured 0.7 +/- 0.4 mm, increased to 1.5 +/- 0.5 mm after rotational atherectomy (p = 0.0013) and to 2.5 +/- 0.3 mm after adjunct directional atherectomy (p < 0.001). The preintervention percent diameter stenosis measured 78 +/- 15%, decreased to 50 +/- 17% after rotational atherectomy (p = 0.0011), and to 17 +/- 11% (p < 0.001) after adjunct directional coronary atherectomy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8456758 TI - Effects on the signal-averaged electrocardiogram of opening the coronary artery by thrombolytic therapy or percutaneous transluminal coronary angioplasty during acute myocardial infarction. AB - One hundred twenty-nine patients were retrospectively analyzed and divided into 3 groups according to (1) the presence of a patent artery obtained either spontaneously or after thrombolytic therapy but without percutaneous transluminal coronary angioplasty (PTCA) (group I, n = 83), (2) the presence of a patent artery after opening by PTCA (group II, n = 29), or (3) absence of reperfusion despite thrombolytic therapy or PTCA (group III, n = 17). Thrombolytic therapy was given within 4 hours after onset of symptoms (mean 2.5 +/- 1.0 hours) and PTCA was performed within 24 hours after the onset of symptoms (mean 6 +/- 6 hours). Signal averaging was performed within 24 hours after cardiac catheterization. An abnormal signal-averaged electrocardiogram was present in 10 of 83 (12%) group I, 9 of 29 (31%) group II and 7 of 17 (41%) group III patients (p < 0.05 group I vs II, p < 0.01 group I vs III, no statistical difference group II vs III). Therefore, in contrast to reperfusion by thrombolytic therapy the incidence of abnormalities on the signal-averaged electrocardiogram early after myocardial infarction is not reduced by an early opening of the culprit vessel by PTCA. PMID- 8456759 TI - A multicenter comparative trial of lovastatin and pravastatin in the treatment of hypercholesterolemia. The Lovastatin Pravastatin Study Group. AB - A randomized, controlled, double-blind trial in 672 hypercholesterolemic patients evaluated the efficacy and safety profile of lovastatin and pravastatin across their usually recommended dosage ranges (lovastatin 20 to 80 mg/day and pravastatin 10 to 40 mg/day). After a 7-week placebo and diet run-in period, patients with low-density lipoprotein (LDL) cholesterol > 160 mg/dl (4.1 mmol/liter) were randomized to 20 mg/day of lovastatin, or 10 mg/day of pravastatin for 6 weeks. The doses were then increased to 40 and 80 mg/day of lovastatin, and 20 and 40 mg/day of pravastatin at weeks 6 and 12, respectively. Efficacy and safety evaluations were performed at weeks 6, 12 and 18. The mean percent changes from baseline in LDL cholesterol at weeks 6, 12 and 18 were -28, 33 and -39%, respectively, with lovastatin, and -19, -25 and -27%, respectively, with pravastatin. All changes were significantly different from 0 (p < 0.001), and the between-group differences were highly significant (p < 0.001). The frequency of adverse events leading to discontinuation was low (2.9% with lovastatin, and 2.4% with pravastatin), with no significant differences between groups. Across the recommended dosage ranges, lovastatin was more effective than pravastatin in reducing total and LDL cholesterol; however, both agents had similar safety profiles. PMID- 8456760 TI - Weekly treatment of diet/drug-resistant hypercholesterolemia with the heparin induced extracorporeal low-density lipoprotein precipitation (HELP) system by selective plasma low-density lipoprotein removal. AB - Heparin-induced extracorporeal low-density lipoprotein (LDL) precipitation (HELP) weekly therapy was evaluated for safety and efficacy in selectively reducing LDL cholesterol levels. Weekly treatments (25) were given to high-risk hypercholesterolemic patients (n = 33) with screening LDL cholesterol levels > 160 mg/dl despite prior diet and drug therapy. Lipids, lipoprotein cholesterol, apolipoproteins A-l and B, and fibrinogen were measured on plasma samples before and after treatment. Mean plasma volume treated was 2.66 liters and mean treatment duration 1.7 hours. Therapy complications were infrequent and were primarily vascular access problems or hypotension. Treatment goals were > 30% LDL cholesterol reduction with each treatment. In 98% of 686 HELP treatments, LDL cholesterol levels were reduced > or = 30%. Mean LDL cholesterol levels were reduced 111.0 mg/dl (54%) with a time-averaged decrease of 39% over a 25-week course. Mean HDL cholesterol was reduced only 6.2 mg/dl (15%). Total cholesterol (134.4 mg/dl; 47% decrease) and apolipoprotein B (88.7 mg/dl; 53% decrease) levels were also reduced. Fibrinogen decreased 158.2 mg/dl (58%) without bleeding complications. HELP therapy can safely and selectively remove plasma LDL cholesterol, producing consistent reductions in LDL cholesterol, total cholesterol and apolipoprotein B levels. PMID- 8456761 TI - Stratification of sudden death risk in patients receiving long-term amiodarone treatment for sustained ventricular tachycardia or ventricular fibrillation. AB - One hundred twenty-two patients treated chronically with amiodarone for sustained ventricular tachycardia or ventricular fibrillation after failing conventional antiarrhythmic therapy were analyzed to determine which factors were predictive of sudden cardiac death during follow-up. The mean left ventricular ejection fraction in the study group was 0.32, and 87% of the patients had coronary artery disease with a prior myocardial infarction. During a median follow-up of 19.5 months, 30 patients died suddenly. The only variable that was predictive of sudden death was left ventricular ejection fraction. Twenty-nine of the 84 patients with ejection fractions < 0.40 died suddenly, compared with 1 of 35 patients with ejection fractions > or = 0.40. The actuarial probability of sudden death at 5 years was 49% when the ejection fraction was < 0.40, and 5% when the ejection fraction was > or = 0.40 (p = 0.0004). These results indicate that patients treated with amiodarone for sustained ventricular tachycardia or ventricular fibrillation whose ejection fractions are > or = 0.40 are at low risk for sudden death. Patients with ejection fractions < 0.40 remain at high risk for sudden death, and should be considered for additional or alternative therapy. PMID- 8456762 TI - Relation between efficacy of radiofrequency catheter ablation and site of origin of idiopathic ventricular tachycardia. AB - The results of radiofrequency catheter ablation of ventricular tachycardia (VT) in patients without structural heart disease are reported. Particular attention was focused on the relation between efficacy and the site of origin of the VT. Eighteen consecutive patients (5 women and 13 men; mean age 41 +/- 13 years) with idiopathic VT underwent catheter ablation using radiofrequency energy. Sites for radiofrequency energy delivery were selected on the basis of pace mapping. A follow-up electrophysiologic test was performed 1 to 3 months after the ablation procedure. Twenty VTs were induced. Radiofrequency catheter ablation was successful in eliminating all 10 VTs originating from the right ventricular outflow tract, and 5 of 10 from other sites in the left or right ventricle. There were no complications. The duration of ablation sessions was shorter, the frequency of identifying a site resulting in an identical pace map was higher, and the efficacy of catheter ablation was greater for VTs originating from the right ventricular outflow tract than for those from other locations. The results of this study demonstrate that radiofrequency catheter ablation of idiopathic VT is safe and effective. The efficacy of the procedure is dependent on the site of origin of the VT, with the efficacy being greater for VTs originating from the outflow tract of the right ventricle than for those from other locations. PMID- 8456763 TI - Endocardial pacing, cardioversion and defibrillation using a braided endocardial lead system. AB - The clinical efficacy and safety of a second-generation braided endocardial pacing, cardioversion and defibrillation lead system was evaluated in 25 patients with ventricular tachycardia (VT) or ventricular fibrillation (VF). The lead system consisted of two 8Fr active fixation endocardial leads each with pacing and defibrillation electrodes and a thoracic patch electrode. Monophasic and biphasic shocks were delivered using a triple-electrode configuration with a right ventricular common cathode and right atrial and thoracic patch anodes. VT and VF were electrically induced. Rapid VT (rate > or = 180 beats/min) and VF were initially terminated by 20 J (550 V) shocks and slow VT (rate < 180 beats/min) by 10 J (400 V) shocks. One hundred fourteen episodes (rapid VT/VF 73, slow VT 41) were treated with 128 shocks (monophasic 80, biphasic 48). Mean ventricular pacing threshold was 0.7 +/- 0.5 ms before and 0.9 +/- 0.5 ms after endocardial shock delivery (p > 0.2). Mean ventricular electrogram amplitude in sinus rhythm was 11.9 +/- 5.7 mV before and 11.4 +/- 5.1 mV after shock delivery (p > 0.2). Simultaneous monophasic endocardial shocks terminated 53% of VF episodes at < or = 20 J. Simultaneous biphasic shocks terminated 94% of all VF episodes at < or = 20 J (p < 0.03). Efficacy of > or = 10 J shocks for rapid VT/VF was greater for biphasic (92%) versus monophasic (74%) shocks (p < 0.05) at lower average shock energy (15 +/- 7 J vs 19 +/- 7 J, respectively, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8456764 TI - Influence of percutaneous mitral commissurotomy on left atrial spontaneous contrast of mitral stenosis. AB - To assess the influence of percutaneous mitral commissurotomy (PMC) on left atrial spontaneous echo contrast of mitral stenosis, transesophageal echocardiography was performed before and 24 to 48 hours after the procedure, and on average, 6 months later in 82 patients. Fifty-nine patients (72%) were in stable sinus rhythm and 23 in permanent atrial fibrillation. Eleven patients (13%) had history of embolism, and 31 were on long-term anticoagulant therapy. The intensity of spontaneous contrast was graded as follows: 0 = no contrast; 1 = slight contrast; and 2 = intense contrast with the typical aspect of "smoke." PMC resulted in a twofold increase in the valve area irrespective of the method of evaluation used (2 cm2 after vs 1.05 before; p < 0.0001). Severe mitral regurgitation occurred in 3 patients who were operated on within 3 months after PMC. Left atrial spontaneous contrast was noted before the procedure in 53 patients (65%). Multivariate analysis showed left atrial size and cardiac index to be predictive factors of its presence (both p < 0.05). At early post-PMC investigation, the incidence of contrast was 50%, and at 6 months, only 28%. Sinus rhythm appeared to be the only independent predictive factor of the disappearance of contrast by multivariate analysis. In patients in atrial fibrillation, the prevalence of spontaneous contrast was 100% before PMC, 91% at early post-PMC investigation (p = NS), and 89% at the late study (p = NS); the rates were 51, 34 (p < 0.005) and 4% (p < 0.0001), respectively, in patients in sinus rhythm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8456765 TI - Rapid redistribution of teboroxime. AB - Teboroxime, a new technetium-99m-labeled myocardial perfusion tracer, possesses rapid myocardial kinetics. Whereas this agent is routinely imaged after separate stress and rest injections, experimental data suggest that teboroxime may rapidly redistribute in the myocardium. Accordingly, we assessed 68 exercise teboroxime scintigrams in which immediate poststress, early delay (5 minutes) and rest images were acquired. Studies were categorized visually as ischemia, infarct or normal based on conventional stress-rest comparison. They were then evaluated for rapid teboroxime redistribution by comparing the stress and early delay images. Quantitative analysis was then performed on 537 myocardial segments. Segments were grouped as ischemia, infarct or normal based on stress-rest comparison, and the degree of normalization of stress-induced defects in the early delay images was determined for each group. Rapid teboroxime redistribution was observed in 20 of 46 scintigrams (48%) considered ischemic, and in 2 of 7 and 2 of 15 scintigrams deemed infarct and normal, respectively. The mean segmental intensity ratio (defined relative to the opposite segment) improved from 0.79 at stress to 0.88 at early delay (p < 0.005) in the group with ischemia and from 0.83 to 0.87 in the group with infarction. The most likely explanation for rapid redistribution of teboroxime is differential washout from the myocardium between areas of disparate flow. It is concluded that rapid redistribution of teboroxime occurs within 5 minutes of a stress injection, giving rise to potentially useful clinical information. Thus, teboroxime imaging should be completed expeditiously to detect areas of relative hypoperfusion. PMID- 8456766 TI - Transgastric continuous-wave Doppler to determine cardiac output. AB - A new method to measure cardiac output using transgastric continuous-wave Doppler was evaluated in 31 consecutive patients undergoing cardiac surgery with simultaneous measurement of cardiac output by the thermodilution technique. A 5 MHz single-plane imaging/5 MHz continuous-wave Doppler transesophageal transducer was used to image the left ventricular outflow tract, aortic valve and ascending aorta from a modified transgastric short-axis plane. The continuous-wave Doppler cursor was aligned parallel with blood flow across the aortic valve to obtain the maximal Doppler velocity spectra. Stroke volume was obtained by multiplying the mean Doppler flow velocity integral by the aortic annulus area, which was calculated from its diameter measured from the esophageal 5-chamber view. The stroke volume was multiplied by heart rate to yield cardiac output. A total of 57 simultaneous thermodilution and Doppler studies were attempted. Doppler data were technically limited for 2 patients both before and after cardiopulmonary bypass and for 3 patients before cardiopulmonary bypass with a result of 50 adequate studies of 57 (88%) attempted. The Doppler-derived cardiac outputs were correlated with the simultaneous measurements of cardiac output by the thermodilution technique. Linear regression analysis revealed a close correlation with R = 0.91, SEE = 0.8 liter/min, and y = 1.01x + 0.2 (p < 0.001). In conclusion, transgastric continuous-wave Doppler across the aortic valve is a promising new technique that may be used in selected patients for accurate measurement of cardiac output. PMID- 8456767 TI - Rotablator to the rescue. PMID- 8456768 TI - Asymptomatic ischemia during predischarge Holter monitoring predicts poor prognosis in the postinfarction period. PMID- 8456769 TI - Comparison of results of rotational coronary atherectomy in three age groups (< 70, 70 to 79 and > or = 80 years). PMID- 8456770 TI - Prognostic value of a normal exercise myocardial perfusion imaging study in patients with angiographically significant coronary artery disease. PMID- 8456771 TI - Examination of restenosis sites in patients with restenosis in one of two previously dilated coronary artery narrowings. PMID- 8456772 TI - Impact of thrombolytic therapy on hemoglobin change after acute myocardial infarction. PMID- 8456773 TI - Biplanar transesophageal echocardiographic direction of radiofrequency catheter ablation in children and adolescents with the Wolff-Parkinson-White syndrome. PMID- 8456774 TI - Relation between pulmonary artery pressure and mitral stenosis severity in patients undergoing balloon mitral commissurotomy. PMID- 8456775 TI - Age-dependent increase in aortic stiffness during negative intrathoracic pressure in healthy subjects. PMID- 8456776 TI - Nonsurgical treatment for a Class III dental relationship: a case report. AB - The purpose of this report is to review the orthodontic treatment of a patient with a Class III malocclusion who was treated nonsurgically with extraction of the mandibular first premolars. The basis for this treatment approach is presented, and the final treatment result reviewed. Important factors to consider when establishing a Class III molar relationship are discussed. PMID- 8456777 TI - Recent advances in understanding mechanically induced bone remodeling and their relevance to orthodontic theory and practice. AB - This review highlights recent developments in bone cell biology, evaluates previous research, and offers future direction toward improving our understanding of events that mediate orthodontic tooth movement. The in vivo and in vitro models that have been developed to examine the responses of connective tissues and how they have contributed to our understanding of the mechanisms involved in mechanically induced bone remodeling are discussed in detail. Osteoblasts are now recognized as the cells that control both the resorptive and the formative phases of the remodeling cycle, and receptor studies have shown them to be the target cells for resorptive agents in bone. The osteoblast is perceived as a pivotal cell, controlling many of the responses of bone to stimulation with hormones and mechanical forces. It is apparent that not all the cellular responses induced by mechanically deformed tissues can be explained by the current paradigm emphasizing the importance of prostaglandin production and cAMP elevation; the mobilization of membrane phospholipids giving rise to inositol phosphates offers an alternative second messenger pathway. It is also argued from circumstantial evidence that changes in cell shape produce a range of effects mediated by membrane integral proteins (integrins) and the cytoskeleton, which may be important in transducing mechanical deformation into a meaningful biologic response. PMID- 8456778 TI - Comments on nonextraction and extraction article. PMID- 8456779 TI - Magnetic activator device II (MAD II) for correction of Class II, division 1 malocclusions. AB - A magnetically active, two-piece (upper and lower), functional orthopedic appliance has been developed, magnetic activator device (MAD) for the correction of Class II malocclusions. The magnetic forces are used to give freedom of mandibular movement and to allow for continuous functioning of the orofacial muscles when the appliance is worn. Samarium cobalt (Sm2Co17) magnets are incorporated on the buccal aspects of the upper and lower appliances. Magnetic forces ranging from 150 to 600 gm per side have been used on patients, and it seems that the skeletal versus dental response depends on the intensity of the magnetic force used. A force of 300 gm, when the magnets are in contact, on each side has been found to be an appropriate value in patients age 7 to 12 years. The use of this less bulky design rather than a traditional orthopedic appliance, along with the freedom of function it permits, has enabled patients to wear the appliance nearly 24 hours in most cases. PMID- 8456780 TI - Epidemiologic and correlation studies of CMD factors: are they all valid according to the scientific method requirements? PMID- 8456781 TI - Static magnetic field effects on the sagittal suture in Rattus norvegicus. AB - Twenty-day-old Wistar albino rats were exposed to static magnetic fields by placing a neodymium-iron-boron magnetic over their sagittal suture. Cellular activity was monitored by the uptake of tritiated thymidine in control, north, south, and unoperated animals at 1, 3, 5, and 10 days (n = 10 per group). A total of 160 animals were used for this part of the study, with the animals examined 1, 3, 5, and 10 days after surgery. Bone remodeling was examined by tetracycline fluorescence with 10 animals allocated to 5- and 10-day periods for north and south poles (n = 10 per group) and control experiments. This consisted of the placement of unmagnetized alloy, similar in size and shape to the magnets, and also included unoperated animals (n = 5 per group). A total of 60 animals were used for the tetracycline study and were examined at 5 and 10 days after surgery. While the tetracycline examination revealed very little change, the thymidine reflected a reduction in thymidine uptake subsequent to placement of the magnet, reaching a maximal effect at 3 days and returning to a normal value thereafter. This questions the potential of static magnetic fields affecting cell mitotic activity as previously reported. PMID- 8456782 TI - Submentovertex cephalometric norms in male Chinese subjects. AB - Submentovertex (SMV) cephalograms of a random sample of 32 male Chinese subjects who were 20.1 +/- 1.9 years old and were free of temporomandibular joint symptoms were studied. A submentovertex cephalometric analysis comprised of 5 angular measurements and 10 linear parameters was developed for the purposes of establishing SMV cephalometric norms among our Chinese adult population for clinical usage. With the exception of condylar angulation, the lack of SMV cephalometric norms published in the literature for other parameters precluded comparison with the results of our study. This new SMV cephalometric analysis can provide clinically relevant information in the treatment of dentofacial orthopedics and facilitate in the diagnosis of mandibular asymmetry. PMID- 8456783 TI - Comparisons of the effectiveness of pliers with narrow and wide blades in debonding ceramic brackets. AB - The removal of most ceramic brackets is accomplished by specially designed pliers that apply some form of tensile or shear force to the tooth surface. While the shear and tensile bond strengths for ceramic brackets in vitro have been reported, a simulation of the actual force application when using sharp-edged debonding pliers to debond a bracket has not. The purpose of this study is to determine the effectiveness and the force levels generated by the use of both the wide and the narrow blades in the debonding of ceramic brackets. The present findings indicate that the narrow blades effectively debonded ceramic brackets with a significantly lower mean debonding force (120 kg/cm2) than the wider blades (150 kg/cm2). The surface area of the blade in contact with the bracket adhesive interface is less for the narrow blade (2.0 mm) than for the wide blade (3.2 mm). This relatively smaller contact area is sufficient to debond a bracket at a significantly lower debonding force. PMID- 8456784 TI - Orthodontic bracket removal using conventional and ultrasonic debonding techniques, enamel loss, and time requirements. AB - The purpose of this study was to examine the effects of ultrasonic orthodontic bracket removal and cleanup and compare them with conventional debonding and cleaning of the enamel surfaces with burs and polishing disks. The amount of enamel loss and time for bracket removal and clean-up were also addressed. Thirty extracted human premolars were collected. The teeth were randomly placed in one of the three debonding groups: debonding with orthodontic pliers and enamel clean up with finishing burs and polishing disks (group 1), debonding with orthodontic pliers and ultrasonic clean-up of the enamel surface (group 2), and ultrasonic debonding enamel clean-up (group 3). The teeth were stored for 48 hours in 100% humidity before bracket removal. All brackets were then removed. Polyvinyl siloxane impressions were made before and after bracket removal. Direct measurements of the teeth in micrometers were made at all steps. An additional 30 teeth were similarly prepared, and the brackets were debonded and cleaned-up as in the three groups previously described. The total time for bracket removal and enamel clean-up for each group was recorded in seconds.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8456785 TI - A tensor analysis to evaluate the effect of high-pull headgear on Class II malocclusions. AB - The inaccuracies inherent in cephalometric analysis of treatment effects are well known. The objective of this article is to present a more reliable research tool in the analysis of cephalometric data. Bookstein introduced a dilation function by means of a homogeneous deformation tensor as a method of describing changes in cephalometric data. His article gave an analytic description of the deformation tensor that permits the rapid and highly accurate calculation of it on a desktop computer. The first part of this article describes the underlying ideas and mathematics. The second part uses the tensor analysis to analyze the cephalometric results of a group of patients treated with high-pull activator (HPA) to demonstrate the application of this research tool. Eight patients with Class II skeletal open bite malocclusions in the mixed dentition were treated with HPA. A control sample consisting of eight untreated children with Class II who were obtained from The Ohio State University Growth Study was used as a comparison group. Lateral cephalograms taken before and at the completion of treatment were traced, digitized, and analyzed with the conventional method and tensor analysis. The results showed that HPA had little or no effect on maxillary skeletal structures. However, reduction in growth rate was found with the skeletal triangle S-N-A, indicating a posterior tipping and torquing of the maxillary incisors. The treatment also induced additional deformation on the mandible in a downward and slightly forward direction. Together with the results from the conventional cephalometric analysis, HPA seemed to provide the vertical and rotational control of the maxilla during orthopedic Class II treatment by inhibiting the downward and forward eruptive path of the upper posterior teeth. The newly designed computer software permits rapid analysis of cephalometric data with the tensor analysis on a desktop computer. This tool may be useful in analyzing growth changes for research data. PMID- 8456786 TI - Nickel hypersensitivity in the orthodontic patient. AB - Nickel is one of the most common causes of allergic contact dermatitis and produces more allergic reactions than all other metals combined. Currently, several brands of orthodontic wires are made of nickel titanium alloy and potentially have a high enough nickel content to provoke manifestations of allergic reactions in the oral cavity. The objectives of this study were (1) to determine if standard orthodontic therapy can sensitize patients to nickel, and (2) to assess gingival response to nickel-containing orthodontic appliances in patients who are nickel sensitive before treatment. Nickel sensitivity patch tests were conducted to confirm hypersensitivity to nickel. Twenty-nine patients from the Division of Orthodontics, Albert Einstein/Montefiore Medical Center were tested, ranging in age from 12 to 48 years. Of the 29 patients, there were 18 female and 11 males. Five of the patients had a positive nickel patch test, a rate of 18.5%. The five patients that tested positive were all female, meaning that the overall rate for females was 27.7% (5:18). The five female patients sensitive to nickel were followed monthly by intraoral photos and gingival and plaque index scores. The remaining patients began routine orthodontic therapy and were retested 3 months into treatment to see whether sensitization occurred. Two patients converted from an initial negative patch test to a positive test. There may be a risk of sensitizing patients to nickel with long-term exposure to nickel containing appliances as occurs in routine orthodontic therapy. PMID- 8456787 TI - Water intoxication and women, infants, and children program. PMID- 8456788 TI - Band-aids or cures? PMID- 8456789 TI - Cholesterol. Myth vs reality in pediatric practice. PMID- 8456790 TI - Cholesterol measurement in children. PMID- 8456791 TI - Effects of nutritional counseling on lipoprotein levels in a pediatric lipid clinic. AB - OBJECTIVE: To determine the impact of nutritional counseling on lipoprotein profiles in dyslipoproteinemic children. DESIGN: Retrospective case review. SETTING: An academic hospital-based pediatric lipid clinic in Boston, Mass. PARTICIPANTS: One hundred four newly referred children with primary dyslipoproteinemia. INTERVENTIONS: Nutritional recommendations were adapted from the National Cholesterol Education Program's step 2 diet. Three-day diet records were used to assess baseline and follow-up diets. RESULTS: Two thirds of the children continued to have excellent diets or improved their diets after counseling, but low-density lipoprotein cholesterol (LDL-c) values decreased by 15% or more in only 19% of children. The observed change in LDL-c was not significantly associated with nutritional counseling. However, a strong correlation was evident between dietary interventions and concentration of high density lipoprotein cholesterol (HDL-c) values in serum. Marked fat restriction lowered HDL-c levels, while liberalization of use of fat, with emphasis on monounsaturates, in a subset of children following an excessively fat-restricted diet on presentation, appeared to improve HDL-c levels. CONCLUSIONS: After nutritional counseling, LDL-c levels decreased by 15% or more in only 19% of dyslipoproteinemic children referred for treatment. There were no clear predictors of LDL-c responsiveness, but changes in dietary fat intake appeared to significantly influence HDL-c levels. PMID- 8456793 TI - The rationale for lowering serum cholesterol levels in American children. AB - The pediatric approach to the primary prevention of coronary artery disease in adults remains controversial. Measurement and intervention to lower serum cholesterol levels have been advocated recently in a selected group of American children by the Expert Panel on Blood Cholesterol Levels in Children and Adolescents of the National Cholesterol Education Program. This article reviews the clinical and scientific data contributing to the controversy surrounding cholesterol in American children. Arguments in favor of and opposed to an aggressive approach to identifying American children with elevated serum cholesterol levels are presented. The rationale for a selective screening approach is demonstrated. PMID- 8456792 TI - Compliance with childhood cholesterol screening among members of a prepaid health plan. AB - OBJECTIVE: To assess compliance with cholesterol screening and intervention by children who were members of a prepaid health plan in which there was no financial barrier to intervention. RESEARCH DESIGN: Children with family histories of hypercholesterolemia, coronary heart disease, and stroke were advised to have a random cholesterol test. Those with total cholesterol levels of 4.80 mmol/L (185 mg/dL) or higher were asked to return for a fasting blood test; of this group, compliant subjects with low-density lipoprotein values of 3.25 mmol/L (125 mg/dL) or higher were offered a nutrition program. SETTING: Kaiser Permanente Medical Center, Oakland, Calif. SUBJECTS AND PARTICIPANTS: The parents of 1160 children aged 2 to 18 years who had routine pediatric appointments at Kaiser Permanente Medical Center were asked to complete screening forms on family history. SELECTION PROCEDURES: Children with family histories of hypercholesterolemia, coronary heart disease, and stroke were advised to have a random cholesterol test. Subjects with total cholesterol levels of 4.80 mmol/L or higher were asked to return for a fasting test, and subjects with low-density lipoprotein levels of 3.25 mmol/L or higher were offered a nutrition program. INTERVENTIONS: Telephone call, letter, low-cholesterol diet, and nutrition program. MAIN OUTCOME MEASURES: Of the 1,160 subjects contacted, 529 (46%) had positive family histories. Of these subjects, random blood cholesterol levels were determined for 369 (70%); 160 (30%) did not comply. Ninety-three subjects had total cholesterol levels of 4.80 mmol/L or higher; of these, 35 (38%) did not comply with follow-up testing. Of the 58 compliant subjects, 25 (43%) had low density lipoprotein values of 3.25 mmol/L or higher and were offered either a 3 week or a 6-week nutrition program. Only nine subjects (36%) enrolled; 16 (64%) did not comply. CONCLUSIONS: Parents do not comply well with a childhood cholesterol screening program that involves two blood tests and moderately intensive educational intervention. Compliance is an important component of cholesterol screening and intervention. PMID- 8456794 TI - Screening for familial hypercholesterolemia in childhood. AB - Widespread blood cholesterol screening in childhood is not an effective strategy for decreasing the burden of coronary heart disease in the US population. Screening to identify older children and adolescents at high risk for developing coronary heart disease in early adulthood makes sense, but only if it is limited to individuals with positive family histories and if the cutoff point for further diagnosis and treatment is set high enough so that the benefits clearly outweigh the risks. These conditions are met for the case of the heterozygous form of familial hypercholesterolemia, which accounts for approximately 5% of cases of premature coronary heart disease. Screening for familial hypercholesterolemia is defensible because of (1) the serious prognosis and relatively high prevalence of familial hypercholesterolemia, (2) the existence of appropriate initial screening and follow-up diagnostic tests, (3) the fact that family history-directed screening is likely to be effective in detecting affected individuals, and (4) the apparent effectiveness of intervention in adolescence for a disease that would otherwise manifest in early adulthood. PMID- 8456795 TI - Ambulatory Pediatric Association, 33rd annual meeting. Washington, D.C., May 4-6, 1993. Abstracts. PMID- 8456796 TI - Regulation of expression of the type I collagen genes. AB - The identification and functional analysis of DNA-protein interactions in the intronic and 5' flanking regions of the type I collagen genes has begun to define a series of cis-elements and trans-acting factors which regulate transcription of these genes. Studies such as these will eventually be expected to elucidate the mechanisms responsible for coordinate transcription of the alpha 1 and alpha 2 genes, a question which remains central to the field of collagen research. Although it is relatively straightforward to define sites of DNA-protein binding, interpretation of the functional importance of such interactions can be extremely complex. Furthermore, while mutation or deletion of a particular binding site may alter the functional activity of a construct transfected into cultured cells, there is no guarantee that a similar change will have the same effect in vivo, where the entire gene locus is present in its native chromosomal context. Nevertheless, these kinds of in vitro studies offer the best current approach to defining and isolating transcription factors that control expression of the alpha 1 and alpha 2 genes. Ultimately, it will be necessary to test the activity of such factors (and their respective cis-elements) in defined systems in vivo. PMID- 8456797 TI - Thermal stability and folding of the collagen triple helix and the effects of mutations in osteogenesis imperfecta on the triple helix of type I collagen. AB - Osteogenesis imperfecta (OI) is an inherited disease in which 90% of the cases result from mutations in the 2 genes, pro alpha 1 and pro alpha 2, coding for type I collagen. Type I collagen is a trimeric molecule, (alpha 1)2 alpha 2, which is dominated both structurally and functionally by the 300 nm triple helical domain. Most OI mutations occur in this domain and almost all point mutations result in the substitution of other amino acids for the obligate glycine which occurs at every third residue. The phenotypic effects of these mutations are frequently attributed in part to alterations in the stability and rate of folding of the triple helix. In order to better understand the relationship between glycine substitutions and stability we review current concepts of the forces governing triple helical stability, denaturational and predenaturational unfolding, and the techniques of measuring stability. From observations on the stability of several collagen types as well as synthetic tripeptides, we present a model for stability based on the contribution of individual and neighboring tripeptide units to the local stability. Although in preliminary form, this empirical model can account for the observed shifts in the Tm of many of the point mutations described. The folding of the triple helix is reviewed. The involvement of peptidyl prolyl cis-trans isomerase in this process in vivo is demonstrated by the inhibition of collagen folding in fibroblasts by cyclosporin A. An hypothesis based on the relationship between the thermal stability at the site of mutation and the propensity for renucleation of folding is proposed. PMID- 8456798 TI - Formation of mineralized nodules by bone derived cells in vitro: a model of bone formation? AB - The identification of the factors which regulate the proliferation and differentiation of cells of the osteoblast lineage remains one of the major challenges in the field of bone cell biology. Although considerable progress has been made in the isolation and culture of cells of the osteoblast lineage from both animal and, more recently, human bone, uncertainties have persisted as to the extent to which these cell populations retain the ability to differentiate into functional osteoblasts in vitro. The formation in vitro of mineralized nodules that exhibit the morphological, ultrastructural and biochemical characteristics of embryonic/woven bone formed in vivo, represents the first evidence that the differentiation of functional osteoblasts can occur in cultures of isolated animal bone-derived cell populations. It is clear, however, that the culture conditions employed at present only permit a small number of cells to differentiate to the extent of being capable of organising their extracellular matrix into a structure that resembles that of bone. Moreover, it has generally been found that the reproducible mineralization of this extracellular matrix requires supplementation of the culture medium with mM concentrations of beta-GP, which raises doubts as to the physiological relevance of this process. The formation of nodules has also been observed in cultures of human bone-derived cells. As found in cultures of animal bone-derived cells, reproducible mineralization of these nodules will occur in the presence of beta-GP. We have shown, however, that in the presence of the long acting ascorbate analogue Asc-2 P, the formation and mineralization of nodules can occur in the absence of beta GP. The nodules formed in human bone-derived cell cultures have yet to be characterized as rigorously as those formed in cultures of animal bone-derived cells and thus it remains to be shown that they resemble bone formed in vivo. PMID- 8456799 TI - In vitro chondrogenesis in human chondrodysplasias. AB - Bone morphogenesis depends on the sequential expression of multiple genes that first allow formation of mesenchymal anlagen, their replacement by cartilage models, and finally, the synthesis of new bone at growth plates. These processes require orchestration of synthesis of multiple collagens, proteoglycans and glycoproteins, the genes for many of which have been isolated and are being studied. Several genes carry mutations which are responsible for the chondrodysplasia phenotypes and can be studied at the gene level or by examining their expression in cultured chondrocytes. PMID- 8456800 TI - Natural history of blue sclerae in osteogenesis imperfecta. AB - Scleral hue is an important sign which distinguishes 2 broad groupings of patients, those with and those without blue sclerae with nonlethal osteogenesis imperfecta (OI). Individuals with OI type I have distinctly blue sclerae which remain intensely blue throughout life. In OI type III and OI type IV the sclerae may also be blue at birth and during infancy, but the intensity fades with time such that these individuals have sclerae of normal hue by adolescence and adult life. PMID- 8456801 TI - Osteogenesis imperfecta: the distinction from child abuse and the recognition of a variant form. AB - Unexplained fractures are characteristic of both osteogenesis imperfecta (OI) and non-accidental injury (NAI) but in most cases the diagnosis is straightforward. However, in a few OI patients an initial diagnosis of NAI is made. Factors contributing to such difficulties include failure to recognise that OI can occur without a family history, without blue sclerae, without osteopenia, without an excess of Wormian bones, or with metaphyseal fractures. In addition we report on 39 patients with an unusual history in that fractures only occurred in the first year of life. Rib fractures, metaphyseal abnormalities and periosteal reactions were common. The initial diagnosis was usually OI if the fractures occurred in hospital, but NAI if they appeared to have been sustained at home. Additional findings such as anaemia, vomiting, hepatomegaly, and apnoeic attacks were often found in these patients. The disorder has some similarities to the syndrome of infantile copper deficiency. Like the latter it is particularly common in preterm infants and in twins. Therefore, we are attempting to examine the incidence of significant hypocupraemia in unselected preterm infants. We suggest that the likely cause of this "temporary brittle bone disease" is a temporary deficiency of an enzyme, perhaps a metalloenzyme, involved in the post-translational processing of collagen. PMID- 8456802 TI - Heritable dentin defects: nosology, pathology, and treatment. AB - Heritable dentin defects have been divided into 2 main categories: dentinogenesis imperfecta (DI) and dentin dysplasia (DD). Recent studies have shown that they share many features in common. Of the connective tissue diseases, only osteogenesis imperfecta (OI) has been linked to these disorders. So far, no definitive relation between the type of OI and the dental involvement can be established. Familial occurrence of DI with OI cannot be comprehensively explained by mutations in type I collagen genes. No information about the gene defects in DD is available. At the ultrastructural level, the organization of the normally cross-striated collagen fibers in the dentin matrix varies markedly in patients affected by DI. PMID- 8456803 TI - Non-invasive prenatal diagnosis of osteogenesis imperfecta. AB - The main mode of non-invasive prenatal diagnosis of osteogenesis imperfecta (OI) is fetal imaging, either by radiography or detailed ultrasonography. Radiography is more of historical interest and ultrasonography is in practice virtually exclusively used for non-invasive second trimester diagnosis of OI. Both methods have also been reported later in pregnancy when diagnosis allows the most appropriate method of delivery to be planned. For example, a caesarean section can be avoided if the fetus is shown to have a form of OI associated with limited survival. Ultrasonography is useful mainly for prenatal diagnosis of the severe forms of OI, especially the perinatally lethal forms (Sillence type II) and to a lesser extent for the severe progressively deforming forms (Sillence types III and III/IV). For the milder varieties of OI (Sillence types I and IV), many cases will be missed by scans. Invasive methods of prenatal diagnosis of OI (principally chorion villous sampling) are used for families with the milder dominant forms of OI and in severe forms of OI in which the actual biochemical or molecular defect in type I collagen is known. Many cases of type II OI and a few of type III have now been reported which were detected by scans before 20 weeks gestation, the earliest being at 15 weeks, for type IIA OI. These include cases not only at genetic risk but also sporadic cases in which scans were done either routinely or for obstetric indications. The ultrasonic abnormalities which are found include reduced echogenicity, multiple fractures, and deformity of the long bones, ribs and skull.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8456804 TI - Psychosocial aspects of osteogenesis imperfecta: an update. AB - Osteogenesis imperfecta (OI) is an inherited disorder in which affected individuals are stigmatized by virtue of physical differences from their peers. The extent to which these differences alter life style depend on the severity of the disorder, its natural history, the extent to which it affects social integration, the effect on physical appearance, and the presence of other affected family members. Some of these factors may adversely influence the ability of affected individuals to effectively adjust to their social and work environment and recognition of these factors may aid individuals and helpers in easing the path to a constructive life. PMID- 8456805 TI - Linkage analysis in dominantly inherited osteogenesis imperfecta. AB - The only serious attempts at linkage in osteogenesis imperfecta (OI) have shown that the disease is linked to type 1 collagen genes in all families studied in which it segregrates as a clear mendelian dominant trait. For prenatal diagnosis the probability that a new family is linked can be taken as greater than 0.95 and this figure is augmented as more meioses are studied. Some phenotype correlations, notably between the OI type IV phenotype and linkage to COL1A2 and between presenile hearing loss in OI type I and linkage to COL1A1, can be used to improve risk estimates substantially in families where there are no segregation data to distinguish whether COL1A1 or COL1A2 is the mutant locus. PMID- 8456806 TI - Molecular heterogeneity in osteogenesis imperfecta type I. AB - Osteogenesis imperfecta (OI) type I is characterized by bone fragility without significant deformity, osteopenia, normal stature, blue sclerae, and autosomal dominant inheritance. Dermal fibroblasts from most affected individuals produce about half the expected amount of type I collagen, suggesting that the OI type I phenotype results from a variety of mutations which alter the apparent expression of either COL1A1 or COL1A2, the genes encoding the chains of type I collagen. Short-pulse labeling of dermal fibroblasts with [3H]proline from affected individuals in 19 families indicates that most have alterations in the expected 2:1 synthetic ratio of pro alpha 1(I): pro alpha 2(I), with most having decreased production of pro alpha 1(I). Ratios of COL1A1:COL1A2 mRNA from these individuals, using slot-blot hybridization, indicate that they fall into different groups, but that most have decreased COL1A1 mRNA levels, compared with controls. These data suggest that most of our OI I families have COL1A1 mutations. Copy number and size of the COL1A1 gene by restriction endonuclease analysis of genomic DNA from affected individuals are normal in the families examined. We have identified one 3 generation family in which all affected members have one normal COL1A1 allele and another with a 5 base-pair deletion near the 3' end of the gene. The deletion creates a shift in the translational reading-frame and predicts the synthesis of an elongated pro alpha 1(I) chain. In a second family, a father and a son have a single exon deletion that results from a splicing mutation. Chemical cleavage analysis of amplified cDNA from affected individuals in different regions of the COL1A1 gene, including the promoter, suggests that several individuals have point mutations within the coding region of the gene, while one individual may have a small deletion within the alpha 1(I) carboxyl-terminal propeptide region. Our data provide evidence for significant molecular heterogeneity within the OI type I phenotype and indicate that a variety of mutations can result in decreased synthesis of type I collagen. PMID- 8456807 TI - Mutations in the COL1A2 gene of type I collagen that result in nonlethal forms of osteogenesis imperfecta. AB - Although virtually all mutations that result in osteogenesis imperfecta (OI) affect the genes that encode the chains of type I procollagen, the effects of mutations in the COL1A2 gene have received less attention than those in the COL1A1 gene. We have characterized mutations in 4 families that give rise to different OI phenotypes. In three families substitutions of glycine residues by cysteine in the triple helical domain (a single example at position 259 and 2 families in which substitution of glycine at 646 by cysteine) have been identified, and in the fourth a G for A transition at position +4 in intron 33 led to use of an alternative splice site and inclusion of 6 amino acids (val-gly arg-ile-leu-phe) between residues 585 and 586 of the normal triple helix. The relation between position of substitution of glycine by cysteine in the COL1A2 gene does not follow the pattern developed in the COL1A1 gene. To determine how COL1A2 mutations produce OI phenotypes, we have produced a full-length mouse cDNA into which we plan to place mutations and examine their effects in stably transfected osteogenic cells and in transgenic animals. PMID- 8456808 TI - Chemical cleavage method for the detection of RNA base changes: experience in the application to collagen mutations in osteogenesis imperfecta. AB - We discuss the definition of mutations in osteogenesis imperfecta (OI) using a chemical cleavage method for detecting mismatched bases in patient mRNA: control cDNA heteroduplexes. The method is based on the increased chemical modification of cytosines (Cs) by hydroxylamine and thymines (Ts) by osmium tetroxide when they are not paired with their complementary base. The DNA is then cleaved at the modified base with piperidine and the use of radioactively labeled DNA probes allows the position of the mismatched base to be determined by electrophoresis of the cleavage-product. The precise mutations are then determined by specific amplification and sequencing of the region containing the mismatched base. In perinatally lethal OI (OI type II) mismatches have been detected in all 17 cases studied; 12 of these have been fully characterized. In 7 of these 12 cases the mismatches were point mutations in the genes for pro alpha 1(I) or pro alpha 2(I) which resulted in glycine substitutions in the triple helical region of the protein. Sequence variation was detected in addition to the glycine substitutions in 2 cases. In 2 cases the RNA mismatch resulted from changes in the amino acid sequence of the C-propeptide domain. In the 3 remaining cases the mismatch resulted from silent nucleotide sequence variants. In the less severe forms of OI we have studied, mismatches have been detected and characterized in 8 of 12 cases. In 4 of these 8 cases the mismatch resulted from presumably neutral sequence variation and in the other 4 cases mutations have been defined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8456809 TI - Moderately severe osteogenesis imperfecta associated with substitutions of serine for glycine in the alpha 1(I) chain of type I collagen. AB - We have examined the type I collagen protein, RNA, and cDNA of 2 children with moderately severe (type IV) osteogenesis imperfecta (OI). They have in common a non-lethal form of OI with ambulatory potential, overmodification of type I collagen protein, and a substitution of serine for glycine in the collagen chain produced by one alpha 1(I) allele. The first child (Marini et al.: J Biol Chem 264:11893-11900, 1989) is now 7 years old, with the height of a 3-year-old. Her course includes significant remodeling of lower long bones and 4 femur fractures. She walks independently. A mishmatch was detected in her alpha 1(I) mRNA using RNA/RNA hybrids; it was demonstrated to be due to a G-->A point mutation in one allele of alpha 1(I), resulting in the substitution of serine for glycine 832. The second child is now 6 1/2 years old, with the height of 1 1/2-year-old. Her history includes significant bowing of femurs and tibias, 6 femur fractures, S curve scoliosis, compression of all lumbar vertebrae, and limited short-distance walking with braces. Her alpha 1(I) mRNA has also been studied by RNA hybrid analysis; there is a single G-->A change in one alpha 1(I) allele causing the substitution of serine for gly 352. Both children have moderately severe OI. However, the serine substitution at gly 352 is associated with a more severe phenotype then is the serine substitution at gly 832. Compared to substitutions described in other cases of OI, the serine 352 is located in the middle of a cluster of cysteine substitutions associated with non-lethal OI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8456810 TI - Somatic cell mosaicism: another source of phenotypic heterogeneity in nuclear families with osteogenesis imperfecta. AB - Mutations in the genes coding for the pro alpha 1 and pro alpha 2 chains of type I procollagen have been found in many patients with osteogenesis imperfecta (OI), a heritable disorder of connective tissue. The severity of the disease varies between families and even among members of the same family. This phenotypic variability covers a spectrum extending from very mild forms that cannot be easily detected to perinatally lethal forms. One explanation for this phenotypic variability is the nature of the mutation in the type I procollagen genes. Another explanation is mosaicism. Here we report on 2 families with propositi who have OI, whereas their mothers had a milder form of the disease. In one family, the molecular defect was previously shown to be a substitution of alpha 1(904) by cysteine [Constantinou et al., 1990]. The biochemical phenotype was characterized by significant post-translational overmodification of the mutated type 1 collagen molecules which also had a 3-4 degrees C decrease in their thermal unfolding. Also, secretion of the procollagen into the culture media was delayed. In the second family, the proposita's muscle fibroblasts synthesized and secreted type I procollagen molecules that were highly over-modified along the entire length of their triple-helical domain. Cells from the mother also synthesized normal and over-modified protein, although the amount of over-modified protein was less than that synthesized by her daughter's cells. The exact molecular defect has not yet been defined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8456811 TI - Possible role of overglycosylation in the type I collagen triple helical domain in the molecular pathogenesis of osteogenesis imperfecta. AB - The underlying defect in patients affected by a form of osteogenesis imperfecta (OI) clarified at the molecular level regards the amount or the structure of type I collagen synthesized. This leads to a decreased and/or abnormal mineral deposition in bone and affects bone mass and/or strength. Abnormal interactions between collagen molecules in the presence of mutant trimers could give rise to abnormal fibrils, which, in turn, can determine incorrect interactions with noncollagenous matrix macromolecules. The interactions can be disturbed or modulated by an abnormal distribution on the collagen fibril surface of electrically charged or hydrophobic groups, or by an increased presence of sugar moieties linked to hydroxylysyl residues due to chain post-translational overmodifications (lysyl overhydroxylation and hydroxylysyl overglycosylation) of the portion of the triple helical domain of abnormal type I collagen molecules N terminal with respect to the defect localization. PMID- 8456812 TI - Collagen fibrils of osteoid in osteogenesis imperfecta: morphometrical analysis of the fibril diameter. AB - Comprehensive electron-microscopic studies showed that the structure of the collagen fibrils in the osteoid is not uniform. In 82 cases of osteogenesis imperfecta (OI), the diameter of the collagen fibrils was determined morphometrically under standardized magnification. The morphometric investigations of collagen fibrils of the osteoid in OI show clear differences in the four subtypes and in comparison with the control group. PMID- 8456813 TI - Immunohistochemical localization of interstitial collagens in bone tissue from patients with various forms of osteogenesis imperfecta. AB - Immunohistochemical studies of bone from individuals with osteogenesis imperfecta (OI) type II, OI type III, or OI type IV demonstrate a similar pattern, but varying extent, of the abnormal presence of interstitial collagens in bone matrix. OI type II bone had nests of cartilage with type II collagen, and significant type III collagen in the bone matrix. In OI types III and IV, type II collagen was present only in epiphyseal cartilage but bone still contained type III collagen. These findings resembled those in developing fetal bone indicating the "immature" nature of OI bone. PMID- 8456814 TI - Osteogenesis imperfecta and hyperplastic callus formation: light- and electron microscopic findings. AB - In rare cases of osteogenesis imperfecta, an "overshoot" growth of new bone may occur, which, clinically gives the impression of a tumour. This condition is known as hyperplastic callus formation. Morphology showed an excessive mixed desmal-chondral osteoneogenesis. Atypical collagen fibrils in non-callus tissue represent an indicator for this callus formation in individual patients. PMID- 8456815 TI - Evaluation of growth hormone axis and responsiveness to growth stimulation of short children with osteogenesis imperfecta. AB - Growth deficiency is a cardinal manifestation of severe Osteogenesis Imperfecta (OI) and occurs frequently in moderate to mild OI. We have investigated the status of the hormones related to growth in 28 children with OI. Our goals were to determine whether there were any abnormalities of these hormones, whether the abnormalities correlated with types of OI, and whether OI bone could be safely stimulated to grow. The study group included 14 females and 14 males. Using the criteria developed by Sillence et al. [1979], 13 children had OI type III, 12 had OI type IV, and 3 had OI type I. Evaluation included 3 standard hGH provocative tests (AITT, L-Dopa), GRF stimulation, 24 hr q20 minute sampling of unstimulated growth hormone, and a somatomedin generation test. All patients except one had normal responses to standard provocative stimuli. Responses to GRF fell into 2 groups: one with a mean response similar to that of normal children, and one with a mean response resembling that of GH deficient children. The group with low response to GRF had a significantly lower area under the curve in the 24-hr test of unstimulated GH than did the normal response group. The OI children as a group showed a blunted IGF-1 response during the Somatomedin Generation Test, with 18/28 children having less than a two-fold stimulation. No test results correlated with OI type. Ten OI children were enrolled in a pilot growth stimulation study. Two children received protropin and 8 received clonidine for at least 6 months. Both children treated with protropin and 4/8 treated with clonidine experienced at least a doubling of their pre-treatment growth rates. Lack of growth hormone response did not correlate with type of OI or parameters from the hormonal evaluation. We speculate that there is a group of OI children who have a hypoactive growth hormone axis. Some OI bone appears to respond to GH and a treatment trial with protropin is planned for a larger number of children. PMID- 8456816 TI - Comprehensive rehabilitation of the child with osteogenesis imperfecta. AB - Children with osteogenesis imperfecta (OI) that results in considerable deformity are often viewed as poor candidates for aggressive physical therapy and rehabilitation. To determine if this view is realistic, we have entered almost 50 children with OI type III and OI type IV into a comprehensive graduated rehabilitation program, based at the National Institutes of Health, but designed to be implemented by continuing involvement of community resources. Children are begun in the program early with emphasis on gain of head and trunk control and progression to sitting and walking, if possible, with the aid of a variety of physical supports, including internal and external bracing. Although not conducted in a randomized fashion, the program's success in bringing children into graded exercise regimes and fostering their increased involvement in school and social situations suggest that aggressive physical therapy and rehabilitation have a major place in the overall care of the infants and children with OI. PMID- 8456817 TI - Early surgical management of severe forms of osteogenesis imperfecta. AB - The early surgical management of severe osteogenesis imperfecta (OI) was studied in three children with autosomal recessive type III form of this disease. Each child had similar clinical and radiographic features at birth. The spine, pelvis, and thorax were osteoporotic but were well formed and free of major fractures. In contrast, the peripheral skeleton was severely affected with numerous new and old fractures. Conservative treatment of fractures was undertaken with a foam mould for the torso and limbs and additional support was provided for specific unstable painful fractures. However, fractures continued due to the extreme bone fragility and deformities. Surgical correction of deformities and internal splinting of the long bones with intramedullary rods was commenced between 18 months and 5 years of age. The shafts of the long bones were extremely fragile and lacked cortical bone. The osteotomies were undertaken with a scalpel. The fracture rate diminished rapidly but the non-extending rods needed shortening or replacing within 2 to 3 years. The combination of external and internal fixation and electric wheel chairs greatly reduced the frequency of fractures and facilitated the general care and development of these 3 children with a severe form of OI. PMID- 8456818 TI - Complications of elongating intramedullary rodding in osteogenesis imperfecta. PMID- 8456819 TI - Fragilitas ossium (fro/fro) in the mouse: a model for a recessively inherited type of osteogenesis imperfecta. AB - The fragilitas ossium (fro/fro) mutation in the mouse has been demonstrated to have clinical, radiographic and morphologic manifestations similar to those which arise in autosomal recessive forms of osteogenesis imperfecta (OI) occurring in humans. Approximately 90% of mutant offspring in the mouse were perinatally lethal with clinical and roentgenographic findings similar to those of OI type II subgroup A in humans. The 10% of mutant mice surviving follow a course very similar to severe progressively deforming OI type III. In surviving mice, there is progressive fore-limb and hind-limb bowing in the absence of a high fracture frequency. PMID- 8456820 TI - Kallmann syndrome associated with complex chromosome rearrangement. AB - We report on a male with Kallmann syndrome (KS) and an apparently balanced complex chromosome rearrangement (CCR): 46,XY,t(3; 9)(9;12)(q13.2;q21.2p13;q15). This is the first known report of a CCR in the KS and the second reported case of a definitive autosomal chromosome abnormality with KS. Possible relationships between the cytogenetic abnormality and KS are discussed. PMID- 8456821 TI - Joubert syndrome associated with Leber amaurosis and multicystic kidneys. AB - We describe a boy with manifestations of Joubert syndrome, Leber congenital amaurosis, and multicystic kidneys. In infants with unexplained neonatal tachypnea and late developmental delay, absence or hypoplasia of the cerebellar vermis should be sought. Joubert syndrome probably is an autosomal recessive disorder. In the subsequent pregnancy of the propositus' mother, we were able to make a prenatal diagnosis of Joubert syndrome, one of the first to be reported. PMID- 8456822 TI - Hearing loss and temporal bone structure in achondroplasia. AB - Characteristic temporal bone changes have recently been defined by high resolution CT in nine patients with achondroplasia (Cobb et al., Am J Neuroradiol 9:1195, 1988). These included narrowing of the skull base and "towering" petrous ridges resulting in abnormal orientation of the inner and middle ear structures. In order to determine whether these morphologic changes are the cause of the hearing deficit in achondroplasia, audiometric studies and ENT evaluation were performed in eight of the nine patients. All had a history of frequent otitis media and four had experienced tympanic membrane tube insertion. Three patients had significant sensorineural hearing loss, two had conductive hearing loss and one patient had combined hearing loss. None of the temporal bone morphologic changes were found to be correlated with the degree of either sensorineural or conductive hearing loss. Fusion of the ossicular chain was not present in any of our cases. Appropriate treatment of frequent acute otitis media and early awareness of middle ear effusions and conductive hearing loss in children with achondroplasia may be of great importance in preventing permanent hearing loss. PMID- 8456823 TI - New epiphyseal stippling syndrome with osteoclastic hyperplasia. AB - We present a lethal skeletal dysplasia characterized radiographically by severe stippling of the lower spine and long bones and periosteal cloaking. In contrast to the normal morphology of the epiphyses and growth plates, the marrow was filled with loose fibrous tissue containing numerous large multinucleated osteoclasts which were associated with Howship's lacunae on the endosteal surface. We suggest the term "Pacman dysplasia" to describe this unusual histologic change that characterizes this new bone dysplasia. PMID- 8456824 TI - Fryns syndrome. AB - We report on a premature female infant with Fryns syndrome who had several less commonly reported anomalies. She had bilateral posterior eventration of the hemidiaphragms instead of the usual diaphragmatic defects with visceral herniation into the chest cavity. She also had a unilateral cleft lip, camptodactyly, duodenal atresia, tracheomalacia, bronchomalacia, and Tetralogy of Fallot. PMID- 8456825 TI - Common fragile site expression in lymphocytes from an individual mosaic for trisomy 8. AB - During the course of a survey of fragile site expression in lymphocytes from twins one member of a dizygotic pair was found to be mosaic for trisomy 8. One hundred fifty metaphases from this individual were analyzed (100 treated with aphidicolin and 50 untreated); 43% were 46,XY and 57% 46,XY,+8. No differences were observed between the treated and control cultures in either the proportions of normal and trisomic metaphases or the overall or specific fragile site expression in the normal and trisomic cells. PMID- 8456826 TI - Symptomatic and asymptomatic methylenetetrahydrofolate reductase deficiency in two adult brothers. AB - We describe two brothers with 5,10-methylene tetrahydrofolate reductase (MTHFR) deficiency. The younger patient first developed limb weakness, incoordination, paresthesiae, and memory lapses at age 15 years, and by his early twenties he was wheelchair bound. His older brother remains asymptomatic at age 37 years. Both had homocystinuria and homocystinemia and low plasma levels of methionine. MTHFR activities in cultured skin fibroblasts of both patients were < 10% control and residual enzyme activities were markedly reduced on heating. The parents had intermediate enzyme activities and the reductase in the father (who had unexplained paraparesis and homocystinemia), but not in the mother, was also thermolabile. Both patients were treated with oral folate and betaine which improved, but did not totally correct, their biochemical abnormality. MTHFR deficiency should be considered in the differential diagnosis of unexplained neurologic disease in adolescents and adults. PMID- 8456827 TI - Inversion (X)(p11.4q22) associated with Norrie disease in a four generation family. AB - We report on a 4-generation family in which Norrie disease occurs together with a pericentric inversion of the X chromosome in all affected males and carrier females. The breakpoint in the short arm of the X chromosome appears to be at the purported location of the Norrie disease gene. This is the second report of an association between Norrie disease and a chromosome aberration involving Xp11, and the first report of a specific gene disruption, thus physical gene location, due to a pericentric chromosome inversion. PMID- 8456828 TI - Familial interstitial deletion 11(p11.12p12) associated with parietal foramina, brachymicrocephaly, and mental retardation. AB - Parietal foramina may be an isolated autosomal dominant trait or found in syndromes. We report on two related individuals who have multiple anomalies with parietal foramina and the deletion of 11(p11.12p12) due to the inheritance of a derivative chromosome 11 from an insertional translocation dir ins (13;11)(q14.1; p11.12p12). Results of initial chromosome analyses on the proposita and her maternal half-uncle were reported as normal. However, the clinical manifestations and family history suggested a chromosomal cause and cytogenetic studies were performed on the proposita's mother. A derivative chromosome 13 was initially identified and further evaluation documented a derivative 11 as the reciprocal product. This family illustrates the importance of performing chromosome studies on the normal intervening relatives in families with multiple affected individuals with mental retardation and minor anomalies as one of the two reciprocal products may be more easily detectable in a balanced carrier. Additionally, the finding of del(11)(p11.12p12) may provide a map location for a syndrome which includes parietal foramina. PMID- 8456829 TI - Age-associated chromosome 21 loss in Down syndrome: possible relevance to mosaicism and Alzheimer disease. AB - We previously observed low level mosaicism (2-4% normal cells) in phytohemagglutinin-stimulated peripheral blood lymphocytes (PBL) in 29% of a small group of elderly persons with Down syndrome (DS). An analysis of cytogenetic data on 154 trisomy 21 cases (age 1 day to 68 years) showed that the proportion of diploid cells in such cultures significantly increased (P < 0.005) with advancing age. Thus, the "occult" mosaicism in PBL of the elderly persons with DS is likely due to the accumulation of cells that have lost a chromosome 21. A consequence of chromosome 21 loss could be uniparental disomy of the 2n cells, a factor that might have significant biological consequences if some chromosome 21 genes are imprinted. Loss of a chromosome 21 from trisomic cells might result in tissue-specific mosaicism and "classical" mosaicism in different age groups. Chromosome 21 loss might also be relevant to the development of Alzheimer-type dementia in DS and in the general population. PMID- 8456830 TI - Aicardi syndrome, metastatic angiosarcoma of the leg, and scalp lipoma. AB - An infant girl with Aicardi syndrome, scalp lipomas, and angiosarcoma of a limb is reported. The cavernous hemangioma of the leg was benign when biopsied at age 5 months but became malignant at 11 months. Angiosarcoma caused multiple distant metastases which were evident at autopsy at age 19 months. This is the first case of Aicardi syndrome associated with lipoma and metastatic angiosarcoma. PMID- 8456831 TI - Premature aging and immunodeficiency: Mulvihill-Smith syndrome? AB - We report on a 30-year-old woman with premature aging, immunodeficiency, and other abnormalities. She had many manifestations of the Mulvihill-Smith syndrome, a disorder that has been described in 4 sporadic individuals, ranging in age from 4 to 17 years. The common manifestations include short stature, microcephaly, a senile face with an underdeveloped lower half, diminished facial subcutaneous fat, multiple pigmented nevi, sensorineural hearing loss, and a low IgG level. Our patient also had severe mental retardation, brachydactyly, severe T cell dysfunction, and suffered from severe verruca vulgaris and a chronic, active Epstein-Barr virus infection. The fact that her parents were first cousins suggests autosomal recessive inheritance of her disorder. Two alternative possibilities were considered: the disorder in the patient represents the Mulvihill-Smith syndrome with immune deficiency as a sign of its advanced stage, or a hitherto undescribed syndrome. PMID- 8456832 TI - In situ hybridization shows direct evidence of skewed X inactivation in one of monozygotic twin females manifesting Duchenne muscular dystrophy. AB - A novel combination of conventional and molecular cytogenetic techniques was used to investigate the expression of an X-linked recessive disorder in one of monozygotic (MZ) twin females. These twins carry a deletion, approximately 300 kb in length, in one of their X chromosomes within the dystrophin gene, which is responsible for Duchenne muscular dystrophy (DMD) in one twin [Richards et al.: Am J Hum Genet 46:672-681, 1990]. A unique DNA fragment generated from an exon within this gene deletion was hybridized in situ to both twins' metaphase chromosomes, a probe which would presumably hybridize only to the normal X chromosome and not to the X chromosome carrying the gene deletion. Chromosomes were identified by reverse-banding (R-banding) and by the addition of 5 bromodeoxyuridine (BrdU) in culture to distinguish early and late replicating X chromosomes, corresponding to active and inactive X chromosomes, respectively. Hybridization experiments showed predominant inactivation of the normal X chromosome in the twin with DMD. This is the first report showing direct evidence at the chromosome level of unequal inactivation of cytogenetically normal X chromosomes resulting in the manifestation of an X-linked recessive disorder in one of monozygotic twin females. This study may now facilitate other research of unequal X inactivation and of females manifesting X-linked recessive disorders. PMID- 8456833 TI - Autosomal dominant multiple cafe-au-lait spots and neurofibromatosis-1: evidence of non-linkage. AB - Multiple cafe-au-lait spots have been observed in successive generations of several families without any other manifestations of neurofibromatosis (NF) or any other systemic disorder. The cafe-au-lait spots in these families segregate as an autosomal dominant trait. The relationship (if any) between the gene for this trait and the NF-1 gene has previously been unknown. We describe a family with five individuals spanning four generations with dominantly inherited cafe-au lait spots, without any other stigmata of NF-1. Linkage analysis with probes proximal, distal, and within the NF-1 gene indicate that the trait in this family is not linked to NF-1. We propose that this condition be called Familial Cafe-Au Lait Spots (FCAL) to distinguish it from the neurofibromatosis syndromes. PMID- 8456834 TI - Duplication 9q34-->qter identified by chromosome painting. AB - We have studied an infant with multiple anomalies and a 46,XY,12p+ karyotype. Parental chromosomes were normal, and it was not possible to determine the identity of the extra material on chromosome 12 cytogenetically. Chromosome painting with probes from a chromosome 9 library identified this material as coming from chromosome 9, and cytogenetics established the duplication as 9q34- >qter. Comparison of this patient with others reported with partial dup(9q) documented excellent concordance of minor anomalies, most notably dolichocephaly, "deep-set" eyes, short horizontal palpebral fissures, beaked nose, micrognathia, arachnodactyly, and developmental delay. Identification of cytogenetically indeterminate abnormalities by molecular cytogenetics is very important, as it permits prognosis to be offered for families of newborn infants with unbalanced karyotypes. PMID- 8456835 TI - Identical twins with Weissenbacher-Zweymuller syndrome and neural tube defect. AB - Neurologic abnormalities have been described only once previously in a child with Weissenbacher-Zweymuller syndrome (WZS), a rare skeletal dysplasia, evident neonatally. We report on identical twin male infants with skeletal findings typical of WZS, including small size at birth, proximal limb shortness, mid face hypoplasia, and myopia. In addition, twin B had a parieto occipital encephalocele while twin A had a meningocele at the same location. Twin B has had significant delays in development and hearing loss. PMID- 8456836 TI - Paternal uniparental disomy in a child with a balanced 15;15 translocation and Angelman syndrome. AB - Chromosome 15 (15q11-q13) abnormalities cause two distinct conditions, Angelman syndrome (AS) and Prader-Willi syndrome (PWS). We present the first case of a child with a balanced 15;15 translocation and AS in whom molecular studies were crucial in confirming a diagnosis. DNA polymorphisms demonstrated paternal uniparental disomy for chromosome 15, consistent with the diagnosis of AS. The molecular studies also showed the patient to be homozygous at all loci for which the father was heterozygous, suggesting that the structural rearrangement was an isochromosome 15q and not a Robertsonian translocation. PMID- 8456837 TI - Complications in the genotypic molecular diagnosis of pseudo arylsulfatase A deficiency. AB - Metachromatic leukodystrophy (MLD) is a severe neurodegenerative disease associated with deficient arylsulfatase A activity. Biochemical confirmation of this disorder has been complicated by a clinically normal but enzymatically deficient variant, pseudo arylsulfatase-A deficiency (PD). The PD mutation is associated with two A-->G transitions in the arylsulfatase A gene. They can be detected simultaneously with a recently developed 3'-mismatch polymerase chain reaction, hence providing a rapid method for genotypic identification and resolving ambiguities of carrier identification based solely on enzyme analyses. However, we now report further genotypic complexities in the molecular diagnosis of PD due to the occurrence of another variant in which only one of the two A-->G mutations of the PD allele was present. This variant confers reduced but readily detectable enzyme activity and behaves as a silent allele in the 3'-mismatch polymerase chain reaction, thus leading to conflicting and erroneous genotype assignments in a family in which both variants and MLD co-exist. The inconsistency was resolved after pedigree validation and further molecular analyses in which the two A-->G mutations were assayed separately with allele specific oligonucleotides. Because arylsulfatase A analysis is one of the most commonly requested lysosomal enzyme assays and the PD mutant allele frequency is high in the general population, complexities as described in this family may be a recurrent problem that can be solved only with combined enzymatic and detailed molecular analyses. PMID- 8456838 TI - ADULT-syndrome: an autosomal-dominant disorder with pigment anomalies, ectrodactyly, nail dysplasia, and hypodontia. AB - We describe a family with at least seven living persons who are affected by an hitherto undescribed autosomal-dominant syndrome with variable expression, bearing close resemblance to the EEC syndrome and related disorders. The main manifestations are hypodontia and/or early loss of permanent teeth, ectrodactyly, obstruction of lacrimal ducts, onychodysplasia, and excessive freckling. We propose the acronym ADULT (acro-dermato-ungual-lacrimal-tooth)-syndrome for this condition. PMID- 8456839 TI - Familial insulin resistant diabetes associated with acanthosis nigricans, polycystic ovaries, hypogonadism, pigmentary retinopathy, labyrinthine deafness, and mental retardation. AB - Two sibs, whose parents are first cousins, had diabetes mellitus with hyperinsulinism, insensitive insulin receptors, and acanthosis nigricans. Both patients had pigmentary retinopathy, secondary cataracts, labyrinthine deafness, mental retardation, and cerebral atrophy. They were disproportionately short with relatively broad hands and feet and slightly coarse face. The young woman had secondary amenorrhea and polycystic ovaries and the boy gynecomastia and hypergonadotrophic hypogonadism. This appears to be the second family with a new autosomal recessive disorder differing from Alstrom syndrome by the presence of mental retardation and absence of renal insufficiency. Impaired insulin receptor binding and polycystic ovaries are described as part of this syndrome. PMID- 8456840 TI - New X-linked syndrome with severe mental retardation, severely impaired vision, severe hearing defect, epileptic seizures, spasticity, restricted joint mobility, and early death. AB - A family with an X-linked mental retardation syndrome involving seven children in two generations is reported. The syndrome includes microcephaly, severe mental retardation, optic atrophy with severely impaired vision or blindness, a severe hearing defect, spasticity, epileptic seizures, restricted movement of the large joints, and death in infancy or early childhood. We conclude that this is a distinct, previously unrecognized X-linked mental retardation syndrome. PMID- 8456841 TI - Severe limb abnormalities: analysis of a cluster of five cases born during a period of 45 days. AB - We report on 5 individuals with severe limb abnormalities born in our hospital within a period of 45 days. Detailed clinical descriptions, photographs, and radiographs are presented. Etiological evaluations included genetic background, obstetric history, invasive procedures during pregnancy, maternal infectious diseases or maternal hyperthermia, drug use before and during pregnancy, and occupational or recreational exposures of both parents. PMID- 8456842 TI - Monozygotic twins concordant for Rubinstein-Taybi syndrome and implications for genetic counseling. PMID- 8456843 TI - Rare alpha 1 antitrypsin allele PI W and a history of infant liver disease. AB - We present a consanguinous couple whose three of four children are homozygous for a rare slow alpha 1 antitrypsin allele PI*W. All three children had abnormal liver function in infancy and two died in infancy of liver disease. The eldest child and both parents were heterozygous for the PI*W allele and were unaffected. Therefore, although serum levels are not markedly reduced, homozygotes appear to be at increased risk of developing liver disease. PMID- 8456844 TI - Multiple craniofacial anomalies associated with an interstitial deletion of chromosome 1(q21->q25). AB - We present a patient with an interstitial deletion of the chromosome 1q21->q25 that was diagnosed by amniocentesis. Significant malformations included: microbrachycephaly, bilateral cleft lip and palate, micrognathia, short neck, and athyroidia. The autopsy results demonstrate an overlap with several other postnatally ascertained patients and document the phenotype prenatally. PMID- 8456845 TI - Paternal age as a risk factor for Down syndrome. AB - Although the effect of maternal age as a risk factor for Down syndrome (DS) is well known, the role of paternal age in the cause of DS has not been clearly established. To investigate this phenomenon we conducted a case-control study between July 1989 and February 1990. The cases were 318 children and teenagers with DS studied at the Specialized Educational Institutions of Lima City, Peru. They were paired with 1,196 control individuals that were selected from the birth records of 2 general hospitals of the city. For each case we tried to obtain 4 controls, paired by their date of birth, sex, and maternal age. The means of paternal age in the 2 groups were compared, first globally and then by groups of maternal age (< 21 years, 21-29 years, 30-34 years, 35-39 years and > 39 years). None of the comparisons gave a statistically significant difference between the 2 groups, using either the Student t-test or the Mann-Whitney U-test. The results obtained in this study give no evidence that paternal age can be considered a risk factor for the conception of a child with DS. PMID- 8456846 TI - Extrahepatic biliary atresia and associated anomalies: etiologic heterogeneity suggested by distinctive patterns of associations. AB - Fifty-one cases of extrahepatic biliary atresia (EHBA) with associated anomalies were found in a study of EHBA (251 cases). Analysis of segregation patterns of these anomalies in individual patients suggested the existence of 2 major groups: (1) 15 cases (29.4%) with various combinations of anomalies within the laterality sequence, and (2) 30 cases (58.8%) with one or 2 anomalies mostly involving the cardiac, gastrointestinal, and urinary systems. These latter anomalies did not follow any recognizable pattern. The third group of 6 cases all had intestinal malrotation, some with preduodenal portal vein; these cases show some similarity to the laterality sequence group and may represent a more confined phenotypic result of faulty situs determination. This previously unattempted classification of patients with EHBA and associated anomalies might enable a more targeted approach towards identification of causes in this heterogeneous disorder. EHBA within the laterality sequence might prove a suitable candidate for a major gene mutation. Teratogenic, infectious and polygenic multifactorial causes might play a more significant role in EHBA associated with "nonsyndromic" organ system anomalies. PMID- 8456847 TI - Reinventing the wheel. PMID- 8456848 TI - Ensuring consumer safety. Predictive testing for Huntington disease: response to Dr. Seymour Kessler, "Reinventing the wheel". PMID- 8456849 TI - Spastic paraplegia, epilepsy, and mental retardation in several members of a family: a novel genetic disorder. AB - We report on a family in which an association between spastic paraplegia and epilepsy has been observed. This disorder is an autosomal dominant trait with incomplete penetrance and variable expressivity. The onset was limited to the first four decades of life; the symptoms were typically those of progressive weakness and spasticity of lower limbs. Epilepsy was present in members of three of the four generations on whom we have information. The concomitance of spastic paraplegia and epilepsy in several members of the same family is unlikely to be fortuitous and probably represents the pleiotropic effect of a single mutant gene. PMID- 8456850 TI - Familial segregation of cervical ribs, Sprengel anomaly, preaxial polydactyly, anal atresia, and urethral obstruction: a new syndrome? AB - In a consanguineous Jewish family originating from Bombay, India, the propositus presented with anal atresia, micropenis, urethral obstruction with secondary prune belly, omphalocele, patent urachus, and cryptorchidism. The kidneys were dysplastic and he had the Potter phenotype with limb deformities. Additional findings included IUGR with microcephaly, congenital heart defects, spinal anomalies, and hypoplastic lungs. The mother and all three sisters had cervical ribs, and she and one sister had 11 pairs of thoracic ribs. The other two sisters had chronic immune thrombopenia. One of those had bilateral Sprengel deformity with homovertebral bones, club feet, and microcephaly and the other sister also had unilateral preaxial hexadactyly. Although familial segregation of cervical ribs and Sprengel deformity has been reported, the association of the findings in this family is unique and may represent a new syndrome. X-linked dominant transmission may explain the severe manifestations in the affected male, but other modes of inheritance may also apply. PMID- 8456851 TI - Balanced reciprocal translocation mosaicism associated with an abnormal phenotype. AB - Balanced reciprocal translocation mosaicism is rarely reported in humans. Only two previous cases have been associated with an abnormal phenotype. We report on a third case of apparently balanced reciprocal translocation mosaicism associated with an abnormal phenotype, largely different from those reported previously. Since low levels of mosaicism may not be detected in routine cytogenetic analyses, balanced reciprocal translocation mosaicism may be associated with an abnormal phenotype more often than has been recognized to date. PMID- 8456852 TI - Progressive malnutrition, severe anemia, hepatic dysfunction, and respiratory failure in a three-month-old white girl. PMID- 8456853 TI - Concurrence of supravalvular aortic stenosis and peripheral pulmonary stenosis in three generations of a family: a form of arterial dysplasia. AB - Isolated supravalvular aortic stenosis (SVAS) commonly is an autosomal dominant trait; it may also occur in the Williams syndrome (WS). While peripheral pulmonary stenosis (PPS) can occur in the same individual with familial isolated SVAS, concurrence of these lesions in different relatives of a family is uncommon. We describe five affected individuals in one family; three had isolated SVAS, one had isolated PPS, and one had SVAS and PPS. Based on this family and review of literature, we suggest that SVAS is a form of arterial dysplasia encompassing PPS in its spectrum. It is developmentally distinct from other left heart obstructive lesions that are hypothesized to be related to blood flow abnormalities in the developing embryo. We also conclude that the clinical disorder in this family represents one that is distinct from WS. PMID- 8456854 TI - X-linked phenotype of absent radius and anogenital anomalies. PMID- 8456855 TI - Craniofacial, limb, and abdominal anomalies in a distinct syndrome: relation to the spectrum of Pfeiffer syndrome type 3. AB - Presented are 2 patients with abnormal craniofacial region, limbs, and abdomen, features that may be consistent with Pfeiffer syndrome, type 3. Both patients had bicoronal and bisphenoidal synostosis, extreme exophthalmic midface hypoplasia, and hydrocephalus. The limbs had a fixed flexion deformity of the elbows with broad thumbs which were radiopalmarly deviated; the toes were broad with a varus deformity and syndactyly toes 2-5. Both patients developed bowel obstruction secondary to midgut malrotation, and one of the patients had prune belly syndrome. Review of the literature disclosed an additional patient who, in retrospect, had Pfeiffer syndrome type 3 and midgut malrotation. These patients suggest that intestinal malrotation with or without prune belly syndrome may be a common component of this entity. PMID- 8456856 TI - Visceral anomalies in the Apert syndrome. AB - We report on visceral anomalies found in 136 patients with Apert syndrome. Autopsies were only performed on 12 of these cases. Thus, the percentage of anomalies found in our patients should be considered a minimum estimate because of the possibility of clinically silent visceral anomalies, minor internal anomalies, and anatomic variations. Cardiovascular and genitourinary anomalies were found most commonly, occurring in 10% and 9.6%, respectively. As expected, complex and multiple cardiac anomalies were frequently associated with early death. Among genitourinary anomalies, hydronephrosis (3%) and cryptorchidism (4.5%, n = 66 males) occurred most commonly. In contrast, anomalies of the respiratory system (1.5%) and gastrointestinal anomalies (1.5%) occurred with lower frequency. The finding of a solid cartilaginous trachea is particularly important because no case was diagnosed during life but rather, only at autopsy. Because cardiovascular and genitourinary anomalies occur with significant frequency, they should be considered in the workup of all Apert newborn infants. We also recommend MRI study of the trachea in any infant with signs and symptoms of lower respiratory compromise. PMID- 8456857 TI - Exstrophy of the cloaca in a 47,XXX child: review of genitourinary malformations in triple-X patients. AB - Cloacal exstrophy, unilateral renal agenesis, and Mullerian anomalies occurred in a liveborn infant with a 47,XXX chromosome constitution. The patient extends the range of genitourinary anomalies reported in triple-X patients. Screening asymptomatic patients for urinary tract abnormalities may be useful in searching for silent malformations potentially associated with this karyotype. PMID- 8456858 TI - Provisionally unique syndrome of ocular and ectodermal defects in two unrelated boys. PMID- 8456859 TI - Holzgreve syndrome: recurrence in sibs. AB - We report on 2 sibs with cardiac and renal abnormalities. The first had hypoplastic left heart sequence and renal hypoplasia; the second had a complex congenital heart defect, renal agenesis, and cleft lip and palate. We suggest that these cases represent the first familial examples of the Holzgreve syndrome. As such, they demonstrate the phenotypic variability seen in sibs, and may serve to further delineate the syndrome. PMID- 8456860 TI - Mosaic dup (9p) diagnosed by fluorescence in situ hybridization (FISH). AB - We describe a girl with some manifestations of the dup (9p) syndrome. High resolution Giemsa-banded karyotype of her lymphocytes documented that she was mosaic with 80% of cells being 46,XX, and 20% 46,XX,-20, + der(20;?) (p13;?). The additional material on 20p could not be defined clearly by high-resolution Giemsa banding, as the banding pattern appeared consistent with either distal 9p or distal 13q. In order to make a definitive cytogenetic diagnosis, we used fluorescence in situ hybridization (FISH) with a chromosome 9 specific DNA library to establish that the origin of the additional chromosomal material on chromosome 20 was from 9p. FISH used in this situation enabled us to counsel the family specifically regarding the prognosis and manifestations of distal 9p duplication. PMID- 8456861 TI - Mosaic 5p tetrasomy. AB - We report on a mildly abnormal 5-year-old girl with seizures, psychomotor retardation, and areas of hyperpigmentation who had a supernumerary marker chromosome in fibroblasts which was identified as an i(5p). To our knowledge, this is the first reported case of tetrasomy 5p. She shares in common some, but not all, manifestations of the dup (5p) syndrome. Cytogenetic analysis of relatives showed that the phenotypically apparently normal mother, maternal grandmother, and a brother of the proband also had a marker chromosome in their lymphocytes which was unrelated to the i(5p). PMID- 8456862 TI - Atypical clinical presentation of ataxia telangiectasia. AB - Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by progressive cerebellar ataxia, oculocutaneous telangiectasias, immunodeficiency with recurrent infections, IgA and IgE deficiency, and increased incidence of malignancies. The pathognomonic biological abnormalities consist of spontaneous chromosomal instability resulting in a high in vivo occurrence of cells with translocations, especially involving chromosomes 7 and 14, and a relative insensitivity of DNA replication in vitro to radiation exposure. We report on a patient with the biological hallmarks of AT but with atypical clinical manifestations. Although progressive cerebellar ataxia was present, the neurological picture was broader than that usually seen in AT and included peripheral polyneuropathy and spinal atrophy. On the other hand, telangiectasias, recurrent infections, malignancies, IgA deficiency, or other immunological abnormalities were not present. This illustrates that the clinical picture of AT is broad and nonspecific, and highlights the diagnostic value of cytogenetic analysis and studies of radioresistance of DNA synthesis. PMID- 8456863 TI - Radioulnar synostosis in Williams-Beuren syndrome: a component manifestation. PMID- 8456864 TI - Growth in Ullrich-Turner syndrome during the pubertal age period. PMID- 8456865 TI - Hydrocephalus in Fanconi anemia. PMID- 8456866 TI - Bazex-Dupre-Christol syndrome: a possible diagnosis for basal cell carcinomas, coarse sparse hair, and milia. PMID- 8456867 TI - Chorionic villus sampling for Rh typing: clinical implications. PMID- 8456868 TI - Zavanelli maneuver for locked twins. PMID- 8456869 TI - Hyperstimulation and the controlled release prostaglandin pessary. PMID- 8456870 TI - Oral magnesium and preterm labor. PMID- 8456871 TI - Depressive disorders after a spontaneous abortion. PMID- 8456872 TI - Questions on prophylactic amnioinfusion as a treatment for oligohydramnios. PMID- 8456873 TI - The paradox of electronic fetal monitoring: more data may not enable us to predict or prevent infant neurologic morbidity. AB - Electronic fetal heart rate monitoring has been used to identify periods of fetal risk, with the hope that clinical intervention would avoid the potential for perinatal death or neurologic damage. A literature review of 10 infant studies failed to document fetal heart rate patterns associated with neurologic injury or protocols for intervention to avoid neurologic injury. A separate analysis of fetal heart rate patterns from 55 brain-damaged infants failed to find consistent patterns that foreshadowed the observed brain injury. These findings should not be surprising, because the majority of infant brain damage occurs outside the intrapartum period and because electronic monitoring may identify times of fetal risk but was never expected to identify brain damage. PMID- 8456874 TI - Should uterine size be an indication for surgical intervention in women with myomas? AB - The quality assurance guidelines published by the American College of Obstetricians and Gynecologists advocate hysterectomy for women with fibroids once the size of the uterus equals or exceeds that at 12 weeks of gestation, regardless of the presence or absence of significant symptoms. Reasons frequently cited by gynecologists for the necessity for surgical intervention include (1) the inability to examine the ovaries, (2) the possible malignancy of the enlarged pelvic mass, (3) the potential for compromise of adjacent organ function if uterine or myomatous growth continues, (4) the greater risks of future surgical treatment if uterine or myomatous growth continues, (5) the potential for greater fertility after surgery on a smaller uterus, and (6) the possibility of continued uterine or myomatous growth resulting from hormone replacement therapy after menopause. A review of the literature reveals surprisingly scant data supporting each of these indications for surgical intervention. The availability of high resolution ultrasonography and magnetic resonance imaging allows for expectant management in many cases where the uterus is at least 12 gestational weeks in size. The presence and severity of myoma-related symptoms should be the most important considerations in the individualization of treatment strategies. PMID- 8456875 TI - Embryoscopic demonstration of hemorrhagic lesions on the human embryo after placental trauma. AB - OBJECTIVE: The purpose of this study was to evaluate embryoscopically the effect of placental trauma on the human embryo. STUDY DESIGN: Patients undergoing elective first-trimester termination of pregnancy underwent transcervical embryoscopy both before and after chorionic villus sampling. If hemorrhagic lesions were not observed on the fetus after chorionic villus sampling, partial placental detachment was performed with a blunt instrument, and the fetus was again observed. RESULTS: Hemorrhagic lesions were observed in 20 of 43 fetuses. In 13 of them, the lesions occurred after placental trauma with the chorionic villus sampling catheter alone (30%), whereas lesions were observed in the remaining seven patients after additional blunt placental disruption. The lesions were located most frequently on the cephalic region, and they grew in size during the observation period. Gestational age or amount of chorionic villus sampling tissue was not different between fetuses with or without lesions. CONCLUSION: Placental trauma results in embryoscopically demonstrable hemorrhagic lesions on the human embryo. Whereas some of these lesions may be of no consequence, others may lead to permanent changes. If similar lesions occur in deeper tissues, they could cause disruptions in development and conceivably could be related to anomalies reported in infants born to women who have had chorionic villus sampling procedures. Embryoscopy affords the opportunity to study possible mechanisms involved in the occurrence of anomalies. PMID- 8456876 TI - Observations of intrapartum fetal activities. AB - OBJECTIVE: The objective of this observational study was to document the frequency of biophysical activities such as breathing and body movements during spontaneous labor in the low-risk, term fetus. STUDY DESIGN: The fetuses of truly low-risk patients without medication during labor were observed serially with real-time ultrasonography for fetal breathing or body movements for a maximum scanning time of 1 hour. Fetal breathing movements, hiccups, and fetal body movements were recorded, as were cervical dilatation, status of the fetal membranes, and Apgar scores. RESULTS: Fetal breathing activity was recorded in 76% of fetuses in early labor and 90% in advanced labor. Fetal body movements were present during 85% of the observations. All babies had 5-minute Apgar scores > 7. CONCLUSION: Ultrasonographic evaluation of fetal breathing and body movements during spontaneous labor was associated with normal birth outcome in this low-risk population. The clinical utility of this noninvasive method in determining intrapartum fetal health remains to be tested in an unselected population. PMID- 8456877 TI - Hysterectomized women with ovarian conservation report more severe climacteric complaints than do normal climacteric women of similar age. AB - OBJECTIVE: Our purpose was to compare the severity of typical climacteric complaints (vasomotor complaints and vaginal dryness) and 21 other complaints, considered atypical for the climacteric, in women with and without a uterus. STUDY DESIGN: A cross-sectional population questionnaire survey was sent to all women aged 39 through 60 years in Ede, the Netherlands. Subjects were 986 hysterectomized women (one or both ovaries present) and 5636 normal women (uterus and both ovaries present). Statistical analysis was performed by cross tabulations, chi 2 analysis, analysis of variance, meta-analysis of variance, and ratios. RESULTS: Hysterectomized women, especially those aged 39 to 41 years, report significantly more vasomotor complaints, vaginal dryness, and atypical complaints than do normal climacteric women of the same age. The higher prevalence of typical climacteric complaints in hysterectomized women largely explains their higher level of atypical complaints. CONCLUSION: Physicians should be alert to typical climacteric complaints after hysterectomy with ovarian conservation, especially in young women, because the literature indicates that hysterectomized women with ovarian conservation are overrepresented with regard to osteoporosis, cardiovascular disease, osteoarthritis, depression, and sexual problems. PMID- 8456878 TI - Impact of climacteric on well-being. A survey based on 5213 women 39 to 60 years old. AB - OBJECTIVE: Our aim was to assess the influence of the severity of vasomotor complaints, menopausal status, and age on the severity of 21 general complaints considered atypical for the climacteric. STUDY DESIGN: A cross-sectional general population survey was conducted through questionnaires of 5213 women aged 39 to 60 years. Statistical analysis was performed by cross tabulation, analysis of variance, and multiple regression analysis. RESULTS: Severity of vasomotor complaints is related to the severity of all 21 general complaints, most pronounced for tenseness and tiredness. Because menstruating women report more severe atypical complaints than nonmenstruating women with similarly severe vasomotor complaints, the change in prevalence of atypical complaints according to menopausal status is rather small. Adjusted for vasomotor complaints, there is virtually no independent effect of age on atypical complaints. CONCLUSIONS: Severity of vasomotor complaints is related to an overall reduced well-being. When climacteric women are seen for atypical complaints it is vital to assess the severity of vasomotor complaints also because others have shown that the severity of vasomotor complaints is indicative of the rate of climacteric bone loss. PMID- 8456879 TI - Simultaneous fetal and maternal cotinine levels in pregnant women smokers. AB - OBJECTIVE: Our purpose was to determine the simultaneous concentrations of serum cotinine in both fetal and maternal blood. STUDY DESIGN: Serum cotinine levels were measured in 11 maternal-fetal pairs at percutaneous umbilical blood sampling. Statistical analysis was performed by means of a one-group t test to determine whether the ratio of fetal-to-maternal cotinine was significantly different from 1. RESULTS: Fetal cotinine levels ranged from 75% to 110% of maternal values (mean ratio 0.90, 95% confidence interval 0.83 to 0.97). Fetal levels were significantly lower than maternal concentrations (p = 0.02). CONCLUSIONS: Cotinine, a metabolite of nicotine used to quantify exposure to tobacco smoke, readily gains access to the fetal circulation. Fetal cotinine concentrations in pregnant women smokers are, on average, 90% of maternal values throughout gestation. PMID- 8456880 TI - Does maternal diabetes delay fetal pulmonary maturity? AB - OBJECTIVE: The purpose of our study was to determine whether a relationship exists between diabetic glucose control and the immaturity rate of fetal pulmonary maturity test results. STUDY DESIGN: One thousand consecutive women who had fetal pulmonary maturity testing before delivery were studied. Diabetic patients were categorized according to whether their diabetes was well controlled or poorly controlled, then compared to the nondiabetic population on the basis of amniocentesis results. RESULTS: Pregnant women with poorly controlled diabetes had a significantly higher risk of immature fetal lung profiles at amniocentesis than did pregnant women without diabetes. Pregnant women with well-controlled diabetes were not significantly different from the nondiabetic population. There was no difference between gestational and pregestational diabetic pregnancies. CONCLUSIONS: Timing of fetal pulmonary maturation is linked to the level of maternal glucose control in diabetic pregnancies. Adequate glucose control may lower the risk of fetal pulmonary immaturity to that seen in the nondiabetic population. PMID- 8456881 TI - Umbilical vessel oxytocin administration for retained placenta: in vitro study of various infusion techniques. AB - OBJECTIVE: The aim of our study was to investigate whether the discrepancies in results between various studies of umbilical vein administration of oxytocin for retained placenta may be related to differences in the infusion techniques used. STUDY DESIGN: An in vitro, descriptive study was performed. Contrast medium was injected into the umbilical vessels of 25 freshly delivered placentas and sequential x-ray films were taken. RESULTS: Capillary filling was inconsistent after injection of 20 ml of solution into the umbilical vein without or with "milking" of the cord (1/5 and 2/5, respectively). These are the techniques most commonly used in reported controlled clinical studies. Injection via an infant mucus aspiration catheter introduced along the umbilical vein to 5 cm from the placental insertion demonstrated a cotyledonary pattern in three of five cases after 20 ml and in all 5 after 30 ml. CONCLUSION: The latter method (use of increased infusion volumes) is recommended in future studies to determine the effectiveness of umbilical vein administration of oxytocin for retained placenta. PMID- 8456882 TI - Automated blood pressure measurements in laboring women: are they reliable? AB - OBJECTIVE: In laboring women a consistent difference has become evident between measurements obtained with an automated blood pressure device and those obtained with the auscultatory method. A prospective study was designed to assess the concordance of these two methods. STUDY DESIGN: Three sets of brachial blood pressure measurements were made by both oscillatory and auscultatory techniques in 30 women in labor, 20 term pregnant women not in labor, and 20 nonpregnant volunteers. RESULTS: In the nonlaboring women and the nonpregnant controls there was satisfactory agreement between the results of the two methods of measurement. In the parturients systolic pressures were consistently and significantly higher and diastolic pressures consistently and significantly lower with the oscillatory compared with the auscultatory method, but mean arterial pressures were not different. CONCLUSION: In laboring women there is a discrepancy between systolic and diastolic pressures obtained by the auscultatory versus the oscillatory method of measurement, although mean pressures are not significantly different. We suggest that during labor the diagnoses of hypertension and hypotension be based on the mean rather than the systolic or diastolic pressure. PMID- 8456883 TI - Multifetal pregnancy reduction by transvaginal puncture: evaluation of the technique used in 134 cases. AB - OBJECTIVE: This report reviews multifetal pregnancy reductions performed transvaginally and tests the feasibility and associated pregnancy loss rates with this technique. STUDY DESIGN: One hundred thirty-four consecutive multifetal pregnancy reductions were analyzed regarding different aspects of total pregnancy losses and complications. The first 40 manually performed were compared with the last 94 procedures performed with an automated puncture device and a thin needle. The losses were also analyzed as a comparison of the reduction of the lower-lying with the higher-lying fetuses located in relation to the internal os. RESULTS: A total uncorrected total pregnancy loss rate of 12.6% and a corrected loss rate of 10.6% was observed. Of the 112 pregnancies in which the lower-lying fetus was reduced, 11 losses were seen. The loss rate in the group reducing the upper fetus was three of 22. The manual versus the puncture device groups showed the same loss rate (10%); however, the manual group had a larger number of subchorionic hematomas after the procedure. CONCLUSIONS: The data are indicative of a very low maternal complication rate (infection) and an acceptable loss rate of the entire pregnancy. The loss rates compare favorable with those for multifetal pregnancy reduction performed transabdominally. PMID- 8456884 TI - Phase II trial of ifosfamide and mesna in patients with advanced or recurrent squamous carcinoma of the cervix who had never received chemotherapy: a Gynecologic Oncology Group study. AB - OBJECTIVE: Our objective was to determine the activity of ifosfamide and mesna in women with advanced or recurrent squamous carcinoma of the cervix who had never received chemotherapy. STUDY DESIGN: This is a phase II drug study in which the starting dose of ifosfamide was 1.5 gm/m2 daily intravenously for 5 days. The starting dose of ifosfamide was reduced to 1.2 gm/m2 daily in patients who had received prior radiotherapy. The uroprotector mesna was given intravenously with, and at 4 and 8 hours after, the administration of ifosfamide. Each dose of mesna was 20% of the total daily dose of ifosfamide. RESULTS: Fifty-six patients were placed in the study; 52 were evaluable for toxicity and 51 for response. Twenty eight (54.9%) patients had previously undergone surgery and 46 (90.2%) had received radiotherapy before this trial. Gynecologic Oncology Group grade 3 or 4 granulocytopenia occurred in 7 (13.5%) patients, and 2 (3.9%) had grade 3 thrombocytopenia. Six (11.5%) patients had grade 3 or 4 neurotoxicity. Complete response was observed in 2 (3.9%) patients and partial responses in 6 (11.5%) patients, for a total response rate of 15.7% (95% confidence interval 7.02% to 28.59%). CONCLUSIONS: This response rate is higher than that reported by the Gynecologic Oncology Group in patients with previously treated squamous carcinoma of the cervix. Our findings fail to confirm that ifosfamide is a highly active agent in patients with squamous carcinoma of the cervix as reported by others; nonetheless, the observed activity of this drug deserves further study in combination therapy of squamous carcinoma of the cervix. PMID- 8456885 TI - Role of the TDx FLM assay in fetal lung maturity. AB - OBJECTIVE: We evaluated the usefulness of the recently introduced TDx FLM assay in determining fetal lung maturity. STUDY DESIGN: The TDx FLM assay was compared with the lecithin/sphingomyelin ratio, the foam stability index, and the presence of phosphatidylglycerol in amniotic fluid samples from 102 pregnancies, among which respiratory distress syndrome developed in 22 infants. RESULTS: The TDx FLM assay met or exceeded results of other tests with respect to sensitivity (100% vs 86% to 100%), specificity (82% vs 38% to 78%), predictive value of a mature test result (100% vs 95% to 100%), predictive value of an immature test result (61% vs 31% to 51%), and efficiency (86% vs 51% to 79%). In a sequential testing strategy the TDx FLM assay performed well as the initial test. Our data indicate that the value for maturity suggested by the manufacturer may be more conservative than necessary. CONCLUSIONS: The TDx FLM assay appears to be a useful test in the field of fetal lung maturity testing. PMID- 8456886 TI - The need to reevaluate trisomy screening for advanced maternal age in prenatal diagnosis. AB - OBJECTIVES: Fluorescence in situ hybridization aneuploidy screening promises immediate results. To evaluate aneuploidy screening in prenatal diagnosis, the prenatal records at Oregon were reviewed. STUDY DESIGN: Karyotype reports of 7240 amniocentesis samples referred for advanced maternal age were retrospectively reviewed for numeric and structural chromosome abnormalities. RESULTS: The frequency of abnormal karyotypes was 2.5%; 1.4% were age-related trisomies and sex-chromosome aneuploids, and 1.1% were non-age-related abnormalities. The incidence of structural rearrangements was 0.9%, of which 70% were familial but not suspected on the basis of family history. CONCLUSIONS: Structural chromosome abnormalities were twice as common as previously reported, representing a significant unrecognized risk for subsequent pregnancies and other family members. Fluorescence in situ hybridization aneuploidy screening would not routinely detect structural chromosome abnormalities, which were twice as frequent as numeric aneuploidy at age 35 years. Routine use of fluorescence in situ hybridization for prenatal diagnosis should not be adopted without a prospective study of its accuracy, reliability, and impact on prenatal diagnosis. PMID- 8456887 TI - Umbilical pressure measurement in the evaluation of nonimmune hydrops fetalis. AB - OBJECTIVE: Nonimmune hydrops fetalis continues to have a perinatal mortality rate > 50%. Although many abnormalities are associated with nonimmune hydrops fetalis, the direct mechanism by which the hydrops occurs is often obscure, even after delivery. There are at least three possible mechanisms for hydrops: heart failure (whether primary or a secondary effect of obstructed venous return), lymphatic malformation, and liver or peritoneal disease. The development of safe access to the fetal circulation by cordocentesis allows for the measurement of the umbilical venous pressure, which is closely related to the fetal central venous pressure. The premise that nonimmune hydrops fetalis of cardiac origin could be distinguished from that of noncardiac origin was examined by measuring the umbilical venous pressure. STUDY DESIGN: Umbilical venous pressure was measured during indicated diagnostic cordocentesis in three groups of fetuses: 20 with nonimmune hydrops fetalis, four with a cardiac malformation but without nonimmune hydrops fetalis, and eight with immune hydrops (fetal hemolytic disease). In 16 of 20 fetuses with nonimmune hydrops fetalis the serum total protein and albumin concentrations were also measured. RESULTS: Presumed inadequate cardiac output, as indicated by an elevated umbilical venous pressure, was the mechanism of nonimmune hydrops fetalis in 13 of 20 (65%). The pathologic condition included arrhythmia, cardiothoracic abnormalities, severe polycythemia and hyperviscosity, viral infection, and severe anemia. Successful antenatal treatment normalized the umbilical venous pressure. Nonimmune hydrops fetalis secondary to noncardiac mechanisms did not progress in severity and was not amenable to antenatal therapy. Hypoproteinemia and hypoalbuminemia were found in only six of 16 cases and were similarly distributed between cardiac and noncardiac mechanisms. CONCLUSIONS: This is the first report where the measurement of umbilical venous pressure was applied to the evaluation of nonimmune hydrops fetalis. Cardiac dysfunction was the most common mechanism causing hydrops. The finding of a normal umbilical venous pressure greatly reduces the likelihood that the heart is the cause of the hydrops, even when there is a coexistent heart malformation. This immediate information allows the practitioner either to focus on therapeutic interventions that might lower the umbilical venous pressure or to look for noncardiac causes for the hydrops. PMID- 8456888 TI - Quality of life of postmenopausal women on a regimen of transdermal estradiol therapy: a double-blind placebo-controlled study. AB - OBJECTIVE: The effect of transdermal estradiol and placebo therapy on the quality of life of postmenopausal women was compared in a randomized trial over 12 weeks. STUDY DESIGN: Two hundred forty-two women were randomized, and 223 were analyzed for efficacy (n = 112 for estradiol and n = 111 for placebo). The quality of life was assessed by means of a battery of standard questionnaires. RESULTS: Quality of life improved after both therapies, but health-related quality of life (p = 0.0003) and well being (p = 0.003) improved more after transdermal estradiol therapy than after placebo. This was also the case for all specific climacteric aspects, including sexual problems (p < 0.0001) and dysfunction (p = 0.01), at comparison with placebo. Self-rated symptom relief was more pronounced with estrogen therapy than with placebo (p < 0.0001). CONCLUSION: It was concluded that estradiol therapy was superior to placebo in relieving symptoms and improving quality of life. PMID- 8456889 TI - Antithyroid antibodies and the association with non-organ-specific antibodies in recurrent pregnancy loss. AB - OBJECTIVES: The purpose of our study was to evaluate the incidence of antithyroid antibodies and non-organ-specific antibodies in women who have had three or more recurrent spontaneous abortions. STUDY DESIGN: Sera from 45 women for the presence of antithyroid antibodies to thyroglobulin and thyroid peroxide and for the non-organ-specific autoantibodies to 6 phospholipids, 5 histones, and 4 polynucleotides were analyzed. Sera from 100 apparently health blood donors served as controls. RESULTS: The test results of 14 (31%) of 45 study subjects were positive for one or both antithyroid antibodies compared with 19 (19%) of controls. Five (11%) of 45 patients had positive test results for one or more non organ-specific antibodies, and 4 (8%) of 45 had positive test results for the lupus anticoagulant by either activated partial thromboplastin, tissue thromboplastin time, or both. Only 3 (21%) of 14 subjects whose test results were positive for thyroid antibodies also demonstrated non-organ-specific autoantibodies. COMMENTS: The incidence of antithyroid antibodies in women who have had recurrent abortions appears not to be significantly increased compared with a normal random control population. Antithyroid antibodies do occur, however, with significantly greater frequencies in women with recurrent spontaneous abortions than non-organ-specific autoantibodies (p = 0.02). Organ specific and non-organ-specific autoantibodies may serve as independent markers of risk for repeated pregnancy loss in patient populations where pregnancy loss is associated with abnormal autoimmune function. PMID- 8456890 TI - A comparison between visual and computer analysis of antepartum fetal heart rate tracings. AB - OBJECTIVE: This study was designed to determine the intraobserver and interobserver variability in the visual assessment of fetal heart rate tracings and to evaluate the accuracy of the visual detection of accelerations and decelerations when compared with computerized fetal heart rate analysis. STUDY DESIGN: One hundred antepartum fetal heart rate tracings, of good quality and of 30 minutes' duration, were visually assessed by five expert observers on three occasions during a 12-month period. There were a total of seven questions related to either judgment or accuracy of each recording. Visual detection of fetal heart rate acceleration, deceleration, and estimated baseline was compared with computerized analysis. Statistical significance was determined by kappa coefficient and contingency table chi 2 analysis. RESULTS: Analysis with kappa coefficient reflecting intraobserver and interobserver agreement of judgment related questions indicated poor agreement between observers when assessing short term fetal heart rate variability (kappa 0.18), when making a decision to stop or continue recording (kappa 0.39), and when judging whether there is concern regarding fetal heart rate tracing (kappa 0.26). When compared with computerized analysis, clinicians had a tendency to recognize tracings as normal. In particular, they failed to identify 35% of tracings with 0 or 1 acceleration and failed to detect 92% of fetal heart rate decelerations. Variable decelerations associated with fetal movements were the major source of disagreement between observers and the computer. Only the estimation of baseline fetal heart rate had a high level of accuracy. CONCLUSION: We concluded that the poor level of accuracy in several components of the nonstress test was responsible for the low interobserver agreement seen in simple judgment-related questions such as decision to continue or stop fetal heart rate recordings. PMID- 8456891 TI - A simple, noninvasive, sensitive method for diagnosis of amniotic fluid embolism by monoclonal antibody TKH-2 that recognizes NeuAc alpha 2-6GalNAc. AB - OBJECTIVE: The sialyl Tn structure (NeuAc alpha 2-6GalNAc alpha 1-O-Ser/Thr) recognized by monoclonal antibody TKH-2 is a characteristic component in meconium and amniotic fluid. The purpose of this study was to determine whether amniotic fluid embolism could be detected by quantification of this antigen in maternal serum by means of an assay using antimucin monoclonal antibody TKH-2. STUDY DESIGN: Sialyl Tn antigen was measured in the serum of women with meconium stained amniotic fluid and compared with the level in those with clear amniotic fluid, as well as that in women with a clinical picture suggesting amniotic fluid embolism. The concentration of sialyl Tn antigen was determined by an immunoradiometric competitive inhibition assay. RESULTS: Serum sialyl Tn antigen levels in women with meconium-stained amniotic fluid (20.3 +/- 15.4 U/ml) at delivery were slightly higher than those in women with clear amniotic fluid (11.8 +/- 5.6 U/ml). A significantly elevated level of sialyl Tn antigen was observed in serum of patients with amniotic fluid embolism and amniotic fluid embolism like symptoms (105.6 +/- 59.0 U/ml, p < 0.01). CONCLUSION: The method for detecting sialyl Tn antigen in the serum of patients with amniotic fluid embolism is a direct way to demonstrate the release of meconium- or amniotic fluid-derived mucin into the maternal circulation and is a simple, noninvasive, sensitive method for diagnosis of amniotic fluid embolism. PMID- 8456892 TI - Role of melatonin in nocturnal prolactin secretion in women with normoprolactinemia and mild hyperprolactinemia. AB - OBJECTIVE: Our objective was to clarify the relationship between the nocturnal melatonin surge and the nocturnal prolactin release in women with normoprolactinemia and mild hyperprolactinemia. STUDY DESIGN: Nocturnal serum melatonin and prolactin levels were determined for a various awake/sleep and light/dark conditions in a total of 23 healthy normoprolactinemia and 9 mild hyperprolactinemia. Patterns of prolactin and melatonin levels were subject to analysis of variance. RESULTS: During sleep deprivation under continuous illumination in normoprolactinemia, neither melatonin nor prolactin increased in concentration. In contrast, during sleep deprivation in a dark environment, both hormones were increased. The maximal prolactin levels in mild hyperprolactinemia under physiologic sleep/dark were significantly higher (p < 0.01) and were reached 2 hours earlier than in normoprolactinemia. However, each woman with mild hyperprolactinemia had similar melatonin surges. Oral administration (1 mg) of melatonin to normoprolactinemia and mild hyperprolactinemia in the daytime resulted in release of prolactin in a fashion similar to that observed during the night. CONCLUSION: Melatonin can regulate nocturnal prolactin secretion independent of sleep-related factors. Furthermore, the nature of the response to exogenous melatonin administration suggests that mild hyperprolactinemia may be unusually sensitive to melatonin. PMID- 8456893 TI - Vaginal delivery of the nonvertex second twin. AB - OBJECTIVE: The purpose of our study was to test the hypothesis that there is no increased morbidity or mortality associated with vaginal delivery of the nonvertex second twin. STUDY DESIGN: The medical records of 781 consecutive twin gestations achieving a gestational age > or = 20 weeks and delivering between Jan. 1, 1985, and Dec. 31, 1988, were reviewed. All live-born, vaginally delivered second twins were identified, grouped by presentation, and compared with respect to 5-minute Apgar scores, length of neonatal hospital stay, neonatal intensive care unit admissions, and neonatal deaths. RESULTS: Of the 390 live born, vaginally delivered second twins, 207 were delivered as vertex and 183 were delivered as breech. Ninety-five percent of the breech deliveries were total breech extractions. There were no statistically significant differences between the vaginal breech and vaginal vertex deliveries in any of the neonatal outcome measures studied even when stratified by birth weight. CONCLUSIONS: These results support the null hypothesis and suggest that vaginal delivery of the nonvertex second twin is a safe intrapartum management option, although no conclusion can be reached in infants weighing < 1500 gm. We found no evidence of excessive morbidity or mortality associated with total breech extraction of the second twin. PMID- 8456894 TI - The effects of indomethacin and terbutaline on human fetal umbilical artery velocimetry: a randomized, double-blind study. AB - OBJECTIVE: Our purpose was to study the effects of indomethacin and terbutaline on umbilical artery impedance as measured by the systolic/diastolic ratio. STUDY DESIGN: Normal, low-risk patients at 26 to 32 weeks' gestation were enrolled. A baseline evaluation of the umbilical artery systolic/diastolic ratio was performed. The patients were then randomized to one of three groups and received a coded capsule that contained either terbutaline (5 mg), indomethacin (50 mg), or placebo. Repeat evaluation of the umbilical artery systolic/diastolic ratio was performed 4 hours later. The ratios before and after administration of the medication were compared in the control and study groups. Analysis of variance and paired Student t test were applied. RESULTS: Fifteen patients received indomethacin, 14 placebo, and 12 terbutaline. Pretreatment and posttreatment systolic/diastolic ratios were 3.2 and 3.1 for the indomethacin group, 3.2 and 3.3 for the placebo group, 3.0 and 2.8 for the terbutaline group, respectively. The changes in the systolic/diastolic ratio in the indomethacin and terbutaline groups, as compared with the placebo group, were not found to be significant. CONCLUSION: Terbutaline and indomethacin do not have a significant effect on the human umbilical artery impedance as measured by the systolic/diastolic ratio. PMID- 8456895 TI - Estrogen and progesterone receptor content in breast epithelial cells from healthy women during the menstrual cycle. AB - OBJECTIVE: Our objective was to analyze the presence of estrogen and progesterone receptors in breast epithelial cells from healthy women during the follicular and luteal phase of the menstrual cycle. STUDY DESIGN: We analyzed estrogen receptor and progesterone receptor variations in breast epithelial cells procured through fine-needle aspiration biopsy from 42 healthy volunteers during the menstrual cycle using immunocytochemical receptor analysis. Differences were assessed by chi 2 test and the Wilcoxon rank sum tests. RESULTS: Estrogen receptor was detected more often in women aspirated in the follicular (68%) than in the luteal (32%) phase (p < 0.001); progesterone receptor was detected in around 80% in both phases. In ovulating women who were aspirated twice during the same menstrual cycle the proportion of estrogen receptor-positive cells was reduced from 20% to 4% (p < 0.02); the progesterone receptor values were 17% and 24%. CONCLUSION: Our data indicate an important difference in progesterone receptor variation in the breast as compared with the endometrium. PMID- 8456896 TI - Emergency peripartum hysterectomy and associated risk factors. AB - OBJECTIVE: Peripartum hysterectomy at Los Angeles County-University of Southern California Medical Center was reviewed and associated risk factors were identified. STUDY DESIGN: Retrospective descriptive and cohort analysis from January 1985 to June 1990 was carried out. Adjusted relative risks for hysterectomy with 95% confidence intervals for identified risk factors were calculated where possible. RESULTS: There were 123 cases of emergency peripartum hysterectomy (incidence of 1.3/1000 births). Indications for hysterectomy were primarily placenta accreta (n = 61), uterine atony (n = 25), unspecified uterine bleeding (n = 19), and uterine rupture (n = 14). The relative risk of emergency hysterectomy was 95.5 (95% confidence interval 66.7 to 136.9) for cesarean delivery, 10.78 (95% confidence interval 7.56 to 15.37) for prior cesarean delivery, and 97.29 (95% confidence interval 70.28 to 134.70) for placenta previa. CONCLUSIONS: Cesarean delivery, prior cesarean delivery, placenta previa, placenta accreta, and uterine atony were identified risk factors for emergency peripartum hysterectomy. PMID- 8456897 TI - Supplementation of vitamin K in pregnant women receiving anticonvulsant therapy prevents neonatal vitamin K deficiency. AB - OBJECTIVE: The null hypothesis of this study is that extra vitamin K administered to pregnant women on a regimen of enzyme-inducing anticonvulsant therapy will not decrease the frequency of symptoms of vitamin K deficiency in their neonates. STUDY DESIGN: A multicenter case-control study was performed on 16 pregnant women on anticonvulsant therapy who received 10 mg of vitamin K1 daily from 36 weeks of pregnancy onward. Concentrations of PIVKA-II (protein induced by vitamin K absence for factor II) and of vitamin K1 were determined in cord blood and compared with those in 20 controls. RESULTS: In none of 17 cord samples was PIVKA II detectable, compared with 13 of 20 in controls (chi 2, p < 0.001). Median cord vitamin K1 level was 530 pg/ml compared with below detection limit in most controls. CONCLUSIONS: Antenatal vitamin K1 treatment decreases the frequency of vitamin K deficiency in neonates of mothers on anticonvulsant therapy. PMID- 8456899 TI - Accuracy of gestational age estimation by means of fetal crown-rump length measurement. AB - OBJECTIVE: The purpose of this study was to develop a gestational age table by means of crown-rump length measurements in the first trimester in pregnancies conceived through in vitro fertilization. STUDY DESIGN: Ninety-four infertile women with singleton intrauterine pregnancies resulting from in vitro fertilization underwent ultrasonographic examinations in the first trimester. The relationship between gestational age (calculated with the day of oocyte retrieval used as day 14) and the crown-rump length was explored with regression analysis. RESULTS: A quadratic model demonstrated the best fit to the data, indicating a curvilinear relationship between crown-rump length and gestational age. Estimates of gestational age with crown-rump length measurements between 40 and 60 mm were observed to be similar to published tables, but outside this range the tables either overestimate or underestimate the true gestational age. CONCLUSION: A more accurate equation for gestational age estimation with crown-rump length measurements in early pregnancy has been developed with in vitro fertilization pregnancy data. PMID- 8456898 TI - 3 beta-hydroxysteroid dehydrogenase deficiency in hyperandrogenism. AB - OBJECTIVE: Deficient adrenocortical 3 beta-hydroxysteroid dehydrogenase activity has been reported in 5% to 30% of hyperandrogenic women. Our objective was to determine the incidence and degree of 3 beta-hydroxysteroid dehydrogenase deficiencies in hyperandrogenism. STUDY DESIGN: A prospective study of adrenal function in patients with hyperandrogenism was performed in a tertiary care university medical center. Eighty-six consecutive patients with hirsutism or hyperandrogenic oligomenorrhea were studied; 26 healthy eumenorrheic women served as controls. All subjects underwent serum sampling at rest and a 1-hour adrenal stimulation test with 1 mg of intravenously corticotropin-(1-24). Dehydroepiandrosterone sulfate, androstenedione, sex hormone-binding globulin, total and free testosterone, and luteinizing and follicle-stimulating hormones were measured in basal serum; dehydroepiandrosterone, 17-hydroxyprogesterone, and 17-hydroxypregnenolone were measured in basal and corticotropin-stimulated serum. On the basis of experience with genetically defined 21-hydroxylase late-onset adrenal hyperplasia, patients were presumed to suffer from 3 beta-hydroxysteroid deficient late-onset adrenal hyperplasia if they demonstrated a dehydroepiandrosterone or 17-hydroxypregnenolone response to corticotropin-(1-24) stimulation (absolute poststimulation level or net increment) greater than threefold the upper 95th percentile of controls. RESULTS: Three women of two families (2.3%) had a 17-hydroxyprogesterone response consistent with 21 hydroxylase-deficient late-onset adrenal hyperplasia and were excluded from further study. Eighteen (21%) of the remaining patients had a 17 hydroxypregnenolone poststimulation increment above the upper 95th percentile of controls (13.9 nmol/L), and two had an elevated dehydroepiandrosterone increment (> 19.5 nmol/L). However, no patient exceeded threefold the upper control limit for either steroid response. Patients with an exaggerated dehydroepiandrosterone or 17-hydroxypregnenolone increment had higher circulating dehydroepiandrosterone sulfate levels but similar basal total and free testosterone, sex hormone-binding globulin, luteinizing and follicle-stimulating hormone concentrations, basal or stimulated androstenedione, dehydroepiandrosterone/androstenedione, and 17 hydroxypregnenolone/17-hydroxyprogesterone than their less responsive counterparts. CONCLUSIONS: Although an exaggerated response of 17 hydroxypregnenolone to adrenal stimulation is common in hyperandrogenism, a response severe enough to merit consideration as 3 beta-hydroxysteroid dehydrogenase-deficient late-onset adrenal hyperplasia was not encountered in this unselected patient population, suggestive of the rarity of this disorder. PMID- 8456900 TI - Transvaginal ultrasonographic characterization of ovarian masses by means of color flow-directed Doppler measurements and a morphologic scoring system. AB - OBJECTIVE: The aim of the study was to test the hypothesis that a combination of a previously devised morphologic scoring system and color flow-directed Doppler measurements would afford better discrimination between benign and malignant ovarian masses. STUDY DESIGN: The scoring system and color flow-directed Doppler measurements for 115 masses were prospectively analyzed and correlated with histopathologic surgical findings. RESULTS: In 21 masses (18 patients) no flow was obtained. Seventy-eight masses in 70 patients were benign, and 16 masses in 12 patients were malignant. The mean total score for the benign masses was 6.7 and for the malignant masses 11.7. The resistance index was 0.64 for the benign lesions and 0.39 for the malignant masses (range 0.2 to 0.98). The mean pulsatility index of the benign masses was 1.17 and 0.52 for the malignancies (range 0.2 to 2.6). There were no malignancies in the group with no flow obtained. The sensitivity and specificity of score alone was 94% and 87%, respectively, with a 60% positive predictive value. By means of resistance index or pulsatility index the sensitivity was 94%, the specificity 99%, and the positive predictive value 94%. CONCLUSION: These results suggest that Doppler flow measurements alone and in conjunction with a scoring system help differentiate benign from malignant masses. PMID- 8456901 TI - Differential protein binding of ceftizoxime in cord versus maternal serum. AB - Ceftizoxime concentrations are higher in cord blood and amniotic fluid than in maternal blood. More avid binding to fetal serum proteins is a suggested mechanism. We measured ceftizoxime protein binding in fetal and maternal blood and documented significantly less protein binding to fetal proteins (21.9% vs 57.8%). PMID- 8456902 TI - Effects of fish oil supplementation in the third trimester of pregnancy on prostacyclin and thromboxane production. AB - OBJECTIVE: Disturbance in thromboxane and prostacyclin biosynthesis has been observed in preeclampsia. We studied whether fish oil supplementation in late pregnancy interferes with maternal and fetal production of thromboxane A2 and prostacyclin I2. STUDY DESIGN: Forty-seven women in the thirtieth week of pregnancy were randomly assigned in a ratio of 2:1:1 to receive fish oil (2.7 gm of n-3 fatty acid per day [Pikasol], or either olive oil or no oil supplementation as controls. Metabolites of thromboxane A2 and A3 and of prostacyclin I2 and I3 were quantified by mass spectrometry methods in serum and urine, respectively. Maternal serum and urine were sampled at baseline, in the thirty-third and thirty-seventh weeks of pregnancy. Fetal serum was sampled at delivery. RESULTS: At the thirty-seventh week the mean concentrations of the eicosapentaenoic-derived metabolites, thromboxane B3 and prostacyclin I3, was twofold to threefold higher (p < 0.001) in the group receiving fish oil compared with combined control groups. There were no significant effects of fish oil on the prostacyclin I2 metabolite, although there was a trend toward a reduction in thromboxane B2 in this group. In umbilical cord blood the mean concentration of thromboxane B2 was lowest in the group receiving fish oil (p = 0.03). CONCLUSIONS: Fish oil was metabolized to the eicosapentaenoic acid-derived eicosanoids thromboxane A3 and prostacyclin I3 in pregnant women. Correspondingly, analog products of arachidonic acid tended to be depressed. It remains to be established whether these biochemical effects will prove beneficial in the prevention or treatment of preeclampsia and intrauterine growth retardation. PMID- 8456903 TI - Increased incidence of neonatal vitamin K deficiency resulting from maternal anticonvulsant therapy. AB - OBJECTIVE: The null hypothesis of our study is that the incidence of vitamin K deficiency in mother-infant pairs exposed to anticonvulsant drugs is not higher than in controls. STUDY DESIGN: In this multicenter observational case-control study, 25 pregnant women receiving anticonvulsant therapy and 25 pregnant controls were studied for PIVKA-II (protein induced by vitamin K absence of factor II) and vitamin K1 concentrations at 32 weeks' gestation and at delivery. RESULTS: PIVKA-II was detectable in 54% of cord samples of the anticonvulsant group and in 20% of controls (chi 2, p = 0.01). In both groups vitamin K1 cord blood levels were predominantly below the detection limit. Maternal vitamin K1 concentrations were lower in women with epilepsy than in controls (Wilcoxon's rank sum test, p < 0.05), but PIVKA-II was rarely present. CONCLUSIONS: The incidence of vitamin K deficiency is increased in neonates exposed to anticonvulsant drugs prenatally. Their mothers, however, are rarely vitamin K deficient. PMID- 8456904 TI - Schauta-Amreich vaginal hysterectomy and Wertheim-Meigs abdominal hysterectomy in the treatment of cervical cancer: a retrospective analysis. AB - OBJECTIVE: The aim of the current study was to determine the effectiveness of Schauta's vaginal hysterectomy in the treatment of stage IB or IIA cervical carcinoma. STUDY DESIGN: In a retrospective analysis the results of Schauta's operation have been compared with those of Meigs' operation in 793 consecutive cases of stage IB or IIA cervical carcinoma. In 201 of them adjuvant radiotherapy was given. A total of 356 patients with stage IB and 76 with stage IIA underwent Schauta's operation, whereas 288 and 64 patients with stage IB and IIA, respectively, were operated on with Meigs' procedure. For statistical analysis the Mantel-Haenszel test was used. RESULTS: In stage IB the 5-year survival (Kaplan and Meier method) was 81% in the Schauta group and 75% in the Meigs group (p < 0.05). The results for stage IIA were 68% and 64%, respectively (difference not significant). In a separate analysis for stage IB and treatment by surgery alone, 5-year survival rates for the 283 in the Schauta group and the 175 in the Meigs group were 83% and 78%, respectively (difference not significant). CONCLUSION: Schauta's vaginal hysterectomy showed a high rate of cure for stage IB or IIA cervical cancer. Therefore we conclude that it can be used as an alternative to the Meigs operation in the presence of obesity or elevated surgical risk. PMID- 8456905 TI - Intrapartum auscultation of the fetal heart rate. AB - A fetal heart rate recording containing a variable deceleration was played for 120 physicians and nurses. Although mean estimates for baseline and nadir of the fetal heart rate and duration of the deceleration were not significantly different from the actual values, individual estimates of the three parameters were widely distributed. Adjunctive techniques for intrapartum fetal heart rate auscultation are recommended. PMID- 8456906 TI - Why do small twins have a lower mortality rate than small singletons? AB - OBJECTIVE: We propose an interpretation of the paradoxically better survival rate among low-birth-weight twins compared with low-birth-weight singletons. STUDY DESIGN: We used data from Belgian birth and death certificates for 1983 and 1984. The data include 229,964 singletons, 2175 first twins, and 2153 second twins. Weight-specific perinatal mortality rates of twins and singletons were compared; the birth-weight distributions were adjusted to a single mean and SD. RESULTS: After adjustment, mortality rates at every weight were higher for twins than for singletons. CONCLUSIONS: The appearance of better survival among small twins compared with small singletons disappears after adjustment to relative birth weight. There is a large risk resulting from twinning that falls on all twins, regardless of their weight. PMID- 8456907 TI - Serum squamous cell carcinoma antigen levels in invasive cervical cancer: prediction of response and recurrence. AB - OBJECTIVE: The rate of normalization of human chorionic gonadotropin or CA 125 in other gynecologic malignancies is highly predictive of response to therapy and recurrence. Serum squamous cell carcinoma antigen (SCC antigen) levels were studied in patients with invasive cervical carcinoma to determine if the rate of normalization was associated with outcome. STUDY DESIGN: One hundred eighty-four patients were studied. A logistic regression of elevated SCC antigen levels was performed. RESULTS: In primary squamous cell carcinoma the SCC antigen level was elevated in stages I, II, III, and IV disease and all stages combined in 24%, 57%, 67%, 71%, and 43% of cases, respectively. Only 27% of patients with nonsquamous carcinoma of the cervix had elevated SCC antigen levels. SCC antigen levels were elevated in 50% of patients with recurrent disease. In both primary and recurrent disease elevated SCC antigen levels decreased with effective therapy. Normalization of elevated SCC levels was associated with a complete response; however, logistic regression of SCC antigen values was not. CONCLUSION: When initially elevated, SCC antigen assays aided in determination of response and detection of recurrences. PMID- 8456908 TI - Accuracy of right ventricular output estimated by Doppler echocardiography in the sheep fetus. AB - OBJECTIVE: Our goal was to determine whether Doppler ultrasonographic estimation of fetal right ventricular output was accurate enough to evaluate fetal cardiac performance before the technique can be applied with confidence to the human fetus. The accuracy of this method has not been validated experimentally. STUDY DESIGN: We compared the right ventricular output measured by Doppler echocardiography with that determined from a transit-time ultrasonic flowmeter placed around the fetal pulmonary trunk and to that determined by microsphere technique. We obtained 72 Doppler flow measurements and 16 microsphere flow measurements in six fetuses. RESULTS: There was a fair correlation between cardiac output estimated by Doppler echocardiography performed transabdominally and that determined by a transit-time flowmeter (r = 0.76). The correlation was excellent when Doppler echocardiography was performed by the trans-uterine approach (r = 0.94). There was also an excellent correlation between right ventricular output determined by a transit-time flowmeter and that by microsphere technique (r = 0.94). CONCLUSION: Doppler echocardiographic estimation of fetal right ventricular cardiac output is thus feasible and accurate. PMID- 8456910 TI - Oxytocin modulates oxytocin neurons in the paraventricular nuclei of female rats throughout pregnancy and parturition. AB - OBJECTIVE: The physiologic roles of nonphasic firing oxytocin neurons in the paraventricular nucleus of female rats throughout pregnancy and parturition was studied from the viewpoint of changes in the membrane activities. STUDY DESIGN: Thin colonal hypothalamic slices containing the paraventricular nucleus were prepared. Immunohistochemical studies of oxytocin in the paraventricular nucleus were performed to determine the localization of oxytocin-containing neurons. Extracellular single neural activities were recorded with a glass micropipette from the oxytocin-dense area, and physiologic concentrations of oxytocin were applied. RESULTS: Nonphasic firing activity was recorded from 61 neurons in virgin female, pregnant, delivering and lactating rats. After bath application of < 5.0 x 10(-11) mol/L of oxytocin, firing rates of 12 of 17 paraventricular neurons in virgin rats decreased and only one increased, whereas the remaining four showed no response to oxytocin. In pregnancy at day 15 all four neurons decreased in activity, whereas at day 21 rats 20 of 26 neurons decreased, two increased, and four showed no response. On the contrary, in delivering rats seven of eight neurons exhibited excitatory responses, and only one showed no response. This excitation reversed to inhibition again after the lactating period ended. CONCLUSION: Negative feedback by oxytocin in virgin and pregnant rats might reverse to positive feedback in delivering and lactating animals as a result of changes in hormonal conditions. This reverse might be closely related to the initiation of delivery. PMID- 8456909 TI - Inhibition of contractions of the isolated human myometrium by potassium channel openers. AB - OBJECTIVE: The aim was to investigate the properties of two potassium channel openers in human myometrium. STUDY DESIGN: The abilities of aprikalim and BRL 38227 to inhibit contractions produced by potassium chloride and oxytocin of myometrial strips from nonpregnant and pregnant women were studied. RESULTS: Aprikalim (1 and 10 mumol/L) and BRL 38227 (1 and 10 mumol/L) suppressed contractions induced by low (10 and 20 mmol/L) but not high (40 and 80 mmol/L) potassium chloride concentrations. Aprikalim and BRL 38227 were also potent relaxants of oxytocin (1 nmol/L)-induced contractions with rapid onset of action, of similar potency to each other, and reversible. Both compounds were significantly more potent against oxytocin (1 nmol/L)-induced contractions in myometrial strips from nonpregnant than from pregnant women. Aprikalim and BRL 38227, as relaxants of oxytocin-induced contractions, were antagonized by glibenclamide (1 mumol/L), a blocker of adenosine 5'-triphosphate-sensitive potassium channels. CONCLUSIONS: The results suggest that aprikalim and BRL 38227 relax the human myometrium by potassium channel opening, possibly at adenosine 5' triphosphate-sensitive potassium channels. Compounds of this pharmacologic class are useful for investigating the physiologic functions of potassium channels in this tissue and could have a place in the treatment of dysmenorrhea and preterm labor. PMID- 8456911 TI - Central anticonvulsant effects of magnesium sulfate on N-methyl-D-aspartate induced seizures. AB - OBJECTIVE: The objective of this study was to determine if magnesium sulfate's central anticonvulsant activity is effective against N-methyl-D-aspartate-induced seizures. STUDY DESIGN: In two separate experiments we investigated magnesium sulfate's ability to inhibit N-methyl-D-aspartate-induced hippocampal seizures in rats. In the first experiment magnesium sulfate was administered peripherally before an intracranial injection of 20 micrograms of N-methyl-D-aspartate. In the second experiment magnesium sulfate was injected intracranially concurrently with N-methyl-D-aspartate. The ability of magnesium sulfate to suppress N-methyl-D aspartate-induced seizure activity under both conditions was assessed. RESULTS: Peripherally administered magnesium sulfate significantly increased the latency from the time of an N-methyl-D-aspartate injection to the first seizure both by acute injection and after 2 hours of sustained elevation of serum magnesium levels when compared with saline solution-injected controls (p < 0.01). The duration of the first seizure was also significantly reduced. Intracranially administered magnesium sulfate significantly (p < 0.01) increased the seizure latency period by 120%. Overall, central magnesium sulfate prevented seizure activity in 40% of the animals (p < 0.01). CONCLUSION: Magnesium sulfate has a central anticonvulsant action on N-methyl-D-aspartate-induced seizures in this rat model of hippocampal seizures. PMID- 8456912 TI - Effect of pregnancy on the vasodepressor response to atrial natriuretic factor. AB - OBJECTIVE: We attempted to determine whether pregnancy alters the vasodepressor response to both physiologic and pharmacologic infusions of atrial natriuretic factor 99-126. STUDY DESIGN: Ten virgin and 10 pregnant (17 +/- 1 days of gestation) conscious, unrestrained Sprague-Dawley rats with chronic indwelling vascular catheters were studied. Mean arterial pressure and heart rate were measured in response to steady-state infusions of either saline solution or increasing concentrations of atrial natriuretic factor (range 5 to 2560 ng.kg 1.min-1). RESULTS: Basal mean arterial pressure was significantly lower in pregnant rats than in virgin rats (89 +/- 3 vs 97 +/- 2 mm Hg, p < 0.02). Atrial natriuretic factor induced significant dose-dependent decreases in mean arterial pressure and heart rate in virgin and pregnant rats (p < 0.001). The hypotensive effects of atrial natriuretic factor were blunted in the pregnant rats only in response to the highest concentrations of atrial natriuretic factor administered (-27 +/- 3 mm Hg in pregnant rats vs -43 +/- 3 mm Hg in virgin rats, p < 0.005). CONCLUSIONS: The vasodepressor response to physiologic infusions of atrial natriuretic factor was not affected by pregnancy status. However, pharmacologic infusions of atrial natriuretic factor resulted in a blunted vasodepressor response in the pregnant animals. This may be due to alterations in vascular atrial natriuretic factor receptors, changes in the clearance rate of atrial natriuretic factor, or the modulating effects of other vasoactive hormones. PMID- 8456913 TI - Placental calcium transport during acute maternal hypermagnesemia in the rat. AB - OBJECTIVE: Our aim was to test the hypothesis that maternofetal placental calcium transfer rate decreases in experimentally induced acute maternal hypermagnesemia in the rat. STUDY DESIGN: We measured the unidirectional maternofetal clearance of calcium 45 and chromium 51-ethylenediaminetetraacetic acid across in situ perfused placentas of rats randomized to intravenous treatment with saline solution and magnesium sulfate (n = 5) or to saline solution only (n = 5) before placental perfusion. The maternofetal clearance of chromium 51 ethylenediaminetetraacetic acid provides a measure of placental "porosity" or passive permeability. RESULTS: The mean serum magnesium concentration increased to 5.3 +/- 0.6 mg/dl (2.18 +/- 0.25 mmol/L) in magnesium-infused rats, staying at 1.8 +/- 0.1 mg/dl (0.74 +/- 0.04 mmol/L) in control rats (p < 0.001). Neither the maternofetal clearance of calcium 45 nor that of chromium 51 ethylenediaminetetraacetic acid was affected by acute maternal hypermagnesemia. CONCLUSION: Within the range of hypermagnesemia studied, placental calcium transport remains unaffected. PMID- 8456914 TI - Perinatal effects of Gardnerella vaginalis deciduitis in the rabbit. AB - OBJECTIVE: We determined the effects of intrauterine infection with Gardnerella vaginalis on maternal and fetal outcome in the rabbit. STUDY DESIGN: Both uterine horns of rabbits on day 20 or 21 of gestation (70% of gestation) were inoculated hysteroscopically with either 0.2 ml of 10(5) to 10(7) CFU/ml of G. vaginalis or saline solution. Animals were killed on day 4 or earlier if premature delivery occurred. The following outcome parameters were evaluated: febrile morbidity, preterm labor and delivery, maternal cultures, fetal birth weight, and fetal neuropathologic findings. RESULTS: G. vaginalis intrauterine inoculation uniformly resulted in amnionitis and deciduitis. Animals inoculated with G. vaginalis had no greater incidence of fever and preterm delivery than did saline treated control animals. However, intrauterine infection with G. vaginalis resulted in a significant decrease in the live birth rate when compared with that of controls (80% vs 95%, p < 0.03). G. vaginalis deciduitis was associated with as 23% reduction in the birth weight of the surviving fetuses. Furthermore, animals in the G. vaginalis study group had a 60% incidence of severe brain injury compared with 0% in the saline solution group. CONCLUSION: G. vaginalis amnionitis and deciduitis produced minimal maternal morbidity but were associated with decreased birth weight and brain injury in surviving fetuses; thus it appears that G. vaginalis selectively functions as a fetal, but not maternal, pathogen in the rabbit. PMID- 8456916 TI - AOTA's Occupational Therapy Buyer's Guide. 1993. PMID- 8456915 TI - Evidence of lasting functional destruction of the rat endometrium after 5 aminolevulinic acid-induced photodynamic ablation: prevention of implantation. AB - OBJECTIVE: We evaluated disruption of endometrial function after treatment with 5 aminolevulinic acid with or without light exposure. STUDY DESIGN: In a conventional laboratory setting adult Sprague-Dawley female rats were treated with various doses of 5-aminolevulinic acid in one uterine horn and saline in the contralateral horn. Three hours after treatment both uterine horns were exposed to light, and the rats were bred to a fertile male 10 or 60 days later. Ablation of endometrium was evaluated by both rate of implantation and histologic features. RESULTS: In the absence of light exposure 5-aminolevulinic acid had no significant effect on the rate of implantation, compared with saline (76% vs 92%, n = 25, p > 0.05). In contrast, 5-aminolevulinic acid treatment plus light exposure profoundly decreased the rate of implantation in the 5-aminolevulinic acid-treated uterine horns of rats bred 10 days (3.8% vs 100%, n = 26, p < 0.001) or 60 days after treatment (16.7% vs 100%, n = 24, p < 0.001). Histologic examination revealed that the 5-aminolevulinic acid plus light-treated uterine horns were completely devoid of endometrium. CONCLUSION: Photodynamic treatment with 5-aminolevulinic acid resulted in a persistent disruption of rat endometrial function and was consistent with the histologic evidence of complete endometrial ablation. In addition, a partial destruction of myometrium adjacent to endometrium was observed. The myometrial damage may be through a nonphotodynamic mechanism because myometrium is unable to synthesize protoporphyrin IX from 5 aminolevulinic acid. PMID- 8456918 TI - Special issue -- Critical issues in functional assessment. PMID- 8456917 TI - Improving functional assessment in occupational therapy: recommendations and philosophy for change. PMID- 8456919 TI - Work evaluations: critique of the state of the art of functional assessment of work. AB - The area of work evaluation is fertile ground for future research and development by occupational therapists. Current evaluations of work range from standardized work evaluations associated with vocational rehabilitation to highly technical physical capacity and work capacity instrumentation and equipment often associated with sports medicine. In addition, methods used to identify pain and abnormal illness behavior add the psychosocial component of work evaluation. The limitations of most of the traditional approaches to work evaluations are their lack of focus on the actual work environments and on the meaning of work to persons. Occupational therapy can play an important and unique role in linking work evaluations to psychosocial and environmental variables and in formulating comprehensive theoretical models of work that should improve and refine present work evaluations. PMID- 8456920 TI - Issues in assessment of psychosocial components of function. AB - For occupational therapy to provide a holistic view of meaningful activity, we must understand the relationship between physical, psychological, and social variables, especially as they affect our psychosocial evaluations and treatment. Existing definitions of psychosocial variables are unclear and, for occupational therapy practice, must be linked to activity and occupational performance. Occupational therapists need to become more educated about the uses and limitations of psychosocial instruments and to develop new instruments that address the central tenets of occupational therapy by focusing on whether or not a person is able to do what is necessary and fulfilling. Further, understanding what is meant by meaningful activity and what people need to accomplish it will advance our effectiveness in occupational therapy assessment and practice. PMID- 8456921 TI - Assessment of play and leisure: delineation of the problem. AB - This paper discusses current perspectives on play and leisure and proposes that if play and leisure are to be accepted as viable occupations, then (a) valid and reliable measures of play must be developed, (b) interventions must be examined for inclusion of the elements of play, and (c) the promotion of play and leisure must be an explicit goal of occupational therapy intervention. Existing tools used by occupational therapists to assess clients' play and leisure are evaluated for the aspects of play and leisure they address and the aspects they fail to address. An argument is presented for the need for an assessment of playfulness, rather than of play or leisure activities. A preliminary model for the development of such an assessment is proposed. PMID- 8456922 TI - Role of physical performance component evaluations in occupational therapy functional assessment. AB - In the 1970s, occupational therapy assessments tended to focus on physical performance component (PPC) evaluations such as strength and range of motion; assessment of occupational performance played a secondary role. Given changes within and outside the profession of occupational therapy, it is time for the assessment of occupation and role performance to assume a primary role, while PPC evaluation should shift to a secondary role. Although PPC evaluations may be less prominent than in the past, they will continue to play an important role in occupational therapy practice and research. Therapists need to be critical consumers of PPC measurement tools because many require further development to validate their use for occupational therapy purposes. PMID- 8456923 TI - Evaluating activities of daily living: directions for the future. AB - Current assessments of simple activities of daily living (ADL) and more complex, instrumental activities of daily living (IADL) could be improved. These assessments are criticized because there are so many different tests for various diagnostic populations, because they rely on self-report rather than observation, because they are based on such varied conceptual frameworks, because they are often cumbersome and lengthy to administer, and because they often rely on outdated or specific cultural perspectives. Improvement of ADL and IADL assessment lies in making them more contextual and client specific, (i.e., by addressing clients' needs in real-life contexts that consider roles, culture, varying environments, and developmental stage. PMID- 8456924 TI - The problem of functional assessment: political and economic perspectives. PMID- 8456925 TI - Functional assessment: toward a dialectical view of person-environment relations. PMID- 8456926 TI - Anticipating the future: assessment of occupational function. AB - I believe that the occupational therapy assessment procedure should reflect our conceptualization of occupational functioning and that there should be a congruence among goals, assessments, and treatment. I believe that there should be a universal occupational therapy intake assessment procedure that follows a top-down approach to clarify for the client that the role of occupational therapy is to promote his or her occupational functioning. All the layers of function that we treat should be assessed, with the particulars of context incorporated into assessments at the activity and higher levels. Further and most important, occupational functioning should be fully conceptualized and the relevant constructs and their relationships verified and made clear to all. PMID- 8456928 TI - Interpersonal skills for practice: an elective course. PMID- 8456927 TI - Continuing challenges of functional assessment in rehabilitation: recommended changes. AB - Many innovative developments are under way to meet the challenges related to appropriate, valid, and practical functional assessment in occupational therapy. There is increasing agreement that occupational therapy's unique contribution to function is through its emphasis on occupational performance. There is also recognition, although limited, that assessing function without regard to the patient's life tasks and roles has serious shortcomings. If we accept that decisions related to intervention and program evaluation are only as good as the information on which they are based, our only option in the face of recognized shortcomings is to dedicate our efforts to develop improved strategies. PMID- 8456929 TI - Even background music can affect listeners. PMID- 8456930 TI - Special issue on feminism laudable, but... PMID- 8456931 TI - Potential role for scavenger receptors of human monocytes in the killing of Schistosoma mansoni. AB - Human low-density lipoproteins (LDL) bind specifically and saturably to the surface of the trematode parasite, Schistosoma mansoni, in vitro. Here we have tested whether human monocytes process the bound LDL. Monocytes obtained by leukapheresis generate H2O2, kill schistosomula, and were seen here endocytosing fluorescently labeled human LDL that was bound to the surface of the parasites. Compounds known to inhibit uptake of LDL via the scavenger receptor, namely, acetylated LDL, polyinosinic acid, dextran sulfate, fucoidan, and polyvinyl sulfate, inhibited both endocytosis of LDL and cell-mediated killing. Non functional analogs of these inhibitors, namely, polycytidylic acid and dextran, did not inhibit either endocytosis or killing. Monocytes obtained from whole blood after venipuncture neither killed the parasite nor endocytosed LDL from the worm surface. Thus, human monocyte killing of schistosomula may involve removal of LDL from the parasite surface via scavenger receptors. PMID- 8456932 TI - An in vivo model of human multidrug-resistant multiple myeloma in SCID mice. AB - We have established a reproducible in vivo model of human multiple myeloma in the severe combined immunodeficient (SCID) mouse using both the RPMI 8226 human myeloma cell line and the P-glycoprotein-expressing multidrug-resistant 8226/C1N subline. SCID mice 5 to 8 weeks of age were injected intraperitoneally with either 8226 drug-sensitive or P-glycoprotein-expressing multidrug-resistant myeloma cells (8226/C1N). Tumors were detected within 5 days after injection by the presence of human lambda light chain excretion in the mouse urine. Growth of the tumor was observed primarily in the abdominal cavity with spread to the abdominal organs. The anti-neoplastic agent doxorubicin was effective in treating the drug-sensitive 8226 human-SCID xenografts but had no effect on the multi-drug resistant 8226/C1N human-SCID xenografts. In the 8226-sensitive xenografts, treatment with doxorubicin resulted in a sharp decline in the concentration of human lambda light chain being excreted in the mouse urine. This correlated with an increased survival of the drug-treated animals. This mouse model offers an in vivo means of evaluating efficacy and toxicity of new therapeutic approaches, including development of chemosensitizers directed against P-glycoprotein in multidrug-resistant myelomas. PMID- 8456933 TI - Schistosomiasis. Infection versus disease and hypersensitivity versus immunity. PMID- 8456934 TI - Two distinct pathological syndromes in male CBA/J inbred mice with chronic Schistosoma mansoni infections. AB - Humans chronically infected with Schistosoma mansoni most commonly present with the relatively asymptomatic intestinal form of the disease, whereas a small minority develop hepatosplenism characterized by severe hepatic disease with portal hypertension. Investigation of hypotheses describing the pathogenic mechanisms underlying the clinical forms of the human disease has been limited by the absence of an animal model that predictably develops such a spectrum of disease. We report that inbred male CBA/J mice that are chronically infected with S. mansoni develop two distinct syndromes, hypersplenomegaly syndrome (HSS) and moderate splenomegaly syndrome (MSS). Pathologically and immunologically, MSS and HSS remarkably parallel the intestinal and hepatosplenic clinical forms, respectively, in humans. HSS affects approximately 20% of these mice and consists of massive splenomegaly, ascites, thymic atrophy, severe anemia, and cachexia. The remaining majority of mice with MSS develop moderate splenomegaly only. Histopathological features of HSS include 1) relatively extensive hepatic fibrosis and granulomatous inflammation, 2) splenic congestion, 3) lymph node plasmacytosis, and 4) worms and eggs in the pulmonary vasculature. Immunologically, the idiotypes present on antisoluble egg antigen antibodies from HSS mice are distinct from those from mice with acute infections or the chronic MSS infection. These idiotypic differences are similar to those observed in patients with intestinal and hepatosplenic forms of the disease and may have regulatory importance. Investigation of the cellular and molecular events that lead to the development of MSS and HSS may advance current understanding of the pathogenesis of the clinical forms of chronic schistosomiasis in humans. PMID- 8456935 TI - Localization of Fos and Jun proteins in rat aortic smooth muscle cells after vascular injury. AB - The availability of specific reagents to measure gene activity has provided important tools and potential new directions for the study of smooth muscle cell (SMC) proliferation in vivo. In this report, we have measured steady-state mRNA levels of several fos and jun family members in aortic tissue by Northern blotting after vascular injury. In addition, protein products of these genes were analyzed by immunocytochemistry. Within 15 minutes of balloon injury, mRNA levels of c-fos, fosB, c-jun, junB, and junD were elevated severalfold. In contrast, fos related antigen (fra-1) mRNA showed a delayed onset of expression. The expression kinetics of these immediate early genes was similar to those in cultured cells stimulated to undergo proliferation by growth factors, suggesting that such SMC gene activation in vivo reflects permeation of blood-derived growth factors into the vessel wall or intravascular release of preformed growth factors. Translation of fos and jun genes into immunoreactive products was demonstrated 2 hours after balloon injury with antisera to Fos and Jun proteins. Treating rats with cycloheximide abolished this immunoreactivity. The distribution of Fos and Jun products was concentrated in SMC nuclei at the luminal border of the rat aorta. Such focal expression may have consequences for the initiation of SMC DNA synthesis and migration after vascular injury. Furthermore, the expression of Fos and Jun proteins in SMC after vascular balloon injury may be used as an index of SMC activation under a variety of experimental settings. PMID- 8456936 TI - Concurrent p53 expression in bronchial dysplasias and squamous cell lung carcinomas. AB - We analyzed the p53 protein immunohistochemically in bronchial dysplasias or squamous cell carcinomas in situ and in squamous cell lung carcinomas occurring in the same patients. The polyclonal antibody used (CM-1) is directed against the wild-type p53 protein, but also recognizes the mutated p53 in formalin-fixed and paraffin-embedded sections. To study the integrity of basement membranes (BMs) and the possible invasion of the dysplastic epithelium, immunostainings for the BM proteins laminin and type IV collagen were used. Nine of the 17 dysplasias showed p53 protein expression (53%); it was significantly more often seen in severe dysplasias and carcinomas in situ than in mild or moderate dysplasias (P = 0.04). The p53 antigenicity was generally located in the basal part of the epithelium. The BMs beneath mildly dysplastic epithelia were continuous. In contrast, those under moderately or severely dysplastic epithelia showed occasional disruptions. p53 protein expression was also found in dysplastic epithelium above a continuous BM suggesting an ominous process before signs of invasion. Twelve of the 17 squamous cell carcinomas showed p53 protein expression (71%). There was a significant concurrent p53 expression in bronchial dysplasias and their related squamous cell carcinomas (P = 0.009), so that all nine cases of p53 positive bronchial dysplasia also showed p53 positivity in the associated squamous cell carcinomas. These findings indicate that p53 protein expression is possible in premalignant bronchial lesions, and suggests that the p53 expression could, at least in some cases, be an early event in the development of a squamous cell carcinoma of the lung. PMID- 8456937 TI - Tissue distribution of very late activation antigens-1/6 and very late activation antigen ligands in the normal thymus and in thymoma. AB - The expression of very late activation antigens (VLAs)-1/6 was correlated with that of the VLA ligands fibronectin, laminin, collagen, and vascular cell adhesion molecule-1 in sections of normal thymus, in thymocyte suspensions, and in 10 cases of thymoma. Capsular epithelial cells are VLA-2+, VLA-3+, and VLA-6+ and face the thymic basement membrane, which is rich in fibronectin, laminin, and collagen type IV. Cortical epithelial cells are VLA-2+ and are embedded in a reticular meshwork of nonorganized extracellular matrix (ECM) that is rich in fibronectin. Cortical thymocytes, identified as CD3dim cells by using immunofluorescence in suspension, are highly positive for VLA-4, a fibronectin ligand. Most cortical macrophages are positive for vascular cell adhesion molecule-1, a molecule recognized by VLA-4. Medullary epithelial cells are VLA 2+/VLA-3+ and are codistributed with fibrous strands of organized ECM that are positive for fibronectin, collagen, and laminin. Medullary thymocytes, identified as CD3bright cells, are positive for VLA-4 and VLA-6, a ligand for laminin. Our findings suggest that intrathymic thymocyte maturation is associated with changes in expression of VLA molecules, which are apparently correlated with the presence of VLA ligands in the tissue microenvironment. Thymomas were classified as cortical (three), common (five), or medullary (two) type. Expression of VLA molecules and distribution of ECM in the three histological subtypes were reminiscent of those observed in the respective regions of the normal thymus. All cases of thymoma were characterized by overexpression of VLA molecules on neoplastic cells, which was associated with increased deposition of organized ECM rich in fibronectin, laminin, and collagen. PMID- 8456938 TI - Extracellular matrix components induce endocrine differentiation in vitro in NCI H716 cells. AB - Endocrine cells occur in +/- 30% of colorectal adenocarcinomas. The significance of this phenomenon in terms of tumor behavior is still controversial. Endocrine differentiation in colorectal cancer cell lines is almost confined to tumor xenografts in vivo, suggesting that endocrine differentiation might be regulated by epithelial-stromal interactions. This hypothesis was studied in the cecal adenocarcinoma-derived cell line NCI-H716 by comparing the expression of chromogranin A protein and messenger RNA in vivo and in vitro and by attempts to induce differentiation in vitro. We found that chromogranin A expression, which was strongest in vivo, could be significantly enhanced in vitro by culturing tumor cells in the presence of native extracellular matrix, on fibroblast feeder layers, and in a defined medium with basic fibroblast growth factor. The results suggest that the extracellular matrix induces endocrine differentiation through factors (e.g., basic fibroblast-growth factor) that may be produced by stromal cells and after secretion bind to the extracellular matrix. PMID- 8456939 TI - Reconstruction of alveolus-like structure from alveolar type II epithelial cells in three-dimensional collagen gel matrix culture. AB - The purpose of this study is to reconstruct an alveolus-like structure from alveolar type II epithelial cells in a culture condition. Isolated alveolar type II epithelial cells of the rat were cultured in a three-dimensional collagen gel matrix. Single type II cells formed cellular aggregates that had a lumen after cell division in this culture condition. Through proliferation of the component cells, these aggregates grew to assume a globular or branching structure, part of which in turn developed into a large, cystic alveolus-like structure. This structure consisted of flattened epithelial cells intermingled with cuboidal epithelial cells. In these structures, the surfactant production was confirmed by immunohistochemistry and electron microscopy. To our knowledge, this is the first report of a reconstruction of an alveolus-like structure in a three-dimensional collagen gel matrix culture. This culture system seems to provide an appropriate physiological environment in which to study the differentiation and disorders of pulmonary alveoli. PMID- 8456940 TI - Macrophages and fibroblasts express embryonic fibronectins during cutaneous wound healing. AB - Fibronectins (FN) comprise a family of adhesive glycoproteins that are prominent components of wound healing. These proteins arise by alternative splicing of a single gene transcript at three sites, termed EIIIA, EIIIB, and V. Extravasated plasma FN, which lacks the EIIIA and EIIIB domains, along with fibrin, comprise the "provisional" matrix that forms within minutes of tissue injury. By 2 days after cutaneous excisional wounding in rats, total FN messenger RNA (mRNA) expression is increased locally and dramatically within the surrounding dermis, in the subjacent muscle (panniculus carnosus) and, notably, at the wound margins. Moreover, in contrast to normal skin, 2-day wounds express EIIIA- and EIIIB containing "embryonic" FN mRNAs. To identify the cells responsible for synthesizing the various FN isoforms, we performed in situ hybridization with probes for the various FN mRNAs. Collagen and lysozyme probes were employed to distinguish fibroblasts from macrophages. At early intervals (2 days) after wounding, macrophages were the principal cells that expressed FN mRNA. Moreover, many of these cells expressed embryonic FN mRNAs. At 7 to 10 days, when the wound defect was maturing, fibroblasts were the major cells synthesizing these embryonic FNs. It is widely accepted that wound macrophages phagocytose debris and provide degradative enzymes and cytokines essential for early stages of tissue repair. Our findings suggest an additional function for wound macrophages- synthesis of embryonic FNs providing an extracellular matrix that facilitates wound repair, perhaps by promoting cell migration. PMID- 8456941 TI - Abnormal fibrillin metabolism in bovine Marfan syndrome. AB - Bovine Marfan syndrome is a disorder that closely resembles human Marfan syndrome in its clinical signs and pathological lesions. The similarities between the human and bovine diseases suggest that similar metabolic defects could be responsible. Although indirect immunofluorescent assays for fibrillin in skin biopsies did not distinguish affected cattle from control animals, cultures of skin fibroblasts of affected animals were distinguished from normal, unrelated control animals and normal half-siblings on the basis of fibrillin staining. After 72 to 96 hours in culture, stained with anti-fibrillin monoclonal antibody 201, hyperconfluent fibroblast cultures of affected cattle had less immunoreactive fibrillin than control cultures, and the staining pattern was granular rather than fibrillar. Under similar culture conditions, normal bovine aortic smooth muscle cells produced large amounts of immunoreactive fibrillin, but smooth muscle cells from a single affected cow showed markedly less fibrillin staining. In pulse-chase metabolic labeling experiments with [35S]cysteine, dermal fibroblasts from 6 affected calves, incorporated far less fibrillin into the extracellular matrix than control cells. These findings are similar to those reported in human Marfan syndrome, and they suggest that the bovine Marfan syndrome, like the human disorder, is caused by a mutation in fibrillin, leading to defective microfibrillar synthesis. PMID- 8456942 TI - FcR+/- subsets of Ia+ pulmonary dendritic cells in the rat display differences in their abilities to provide accessory co-stimulation for naive (OX-22+) and sensitized (OX-22-) T cells. AB - A substantial body of evidence indicates that the primary sensitization of naive T cells to inhaled antigens occurs in the regional lymph nodes, whereas secondary responses may be generated directly within lung tissue. Ia+ pulmonary dendritic cells are widely distributed within the rat lung where they can participate in the induction of the immune response to inhaled antigens. Recently, two subsets of Ia+ pulmonary dendritic cells have been distinguished based on their expression of Fc receptors (FcR), but little is known concerning their abilities to support the responses of naive or sensitized T cells. In order to address this question, pulmonary FcR+/- dendritic cells have been purified from enzymatic digests of Lewis rat lungs, based on their differential binding to heat aggregated immunoglobulin. The FcR+/- dendritic cell subsets differed with respect to their light microscopic appearance and in their expression of non specific esterase. Only the FcR+ subset was able to phagocytize latex beads and showed intracellular phagolysosomes by electron microscopy. Both of the FcR+/- subsets rapidly formed clusters with naive (OX-22+) and sensitized (OX-22-) T cells. However, the clusters yielded by the FcR+ subset were substantially smaller, possibly reflecting their diminished surface membrane expression of the intercellular adhesion molecule-1. The FcR+/- subsets were capable of presenting soluble and particulate antigens to OX-22- T cells. FcR+ cells were less effective than FcR- cells in promoting the proliferative response of OX-22+ T cells to concanavalin A and in the primary mixed leukocyte reaction. We conclude that the FcR+/- pulmonary dendritic cells differ in their abilities to support the responses of naive and sensitized T lymphocytes. This observation may have significance for how primary and secondary pulmonary cell-mediated immune responses are generated. PMID- 8456943 TI - Intraglomerular basement membrane translocation of immune complex (IC) in the development of passive in situ IC nephritis of rats. AB - A study was performed to elucidate the mechanisms of charge-based immune complex nephritis. A chronological observation after induction of nephritis was made by immunoelectron microscopy to clarify whether antigen (Ag) remains in association with antibody (Ab) and C3 during the translocation through the glomerular basement membrane (GBM). Fifteen minutes after intrarenal perfusion with cationized ferritin (pI > 10.0) as Ag, followed by injection of rabbit anti ferritin Ab, deposition of subendothelial Ag-Ab-C3 complexes was observed. Between 2 hours and 1 day, a large number of Ag in close association with Ab was noted in the lamina densa, but only a small amount of C3 was detectable. During this time Ag and Ab in the subendothelial region gradually decreased. However, C3 reappeared in the subepithelial region together with the Ag-Ab complex after 1 day, and the subendothelial C3 significantly decreased. At 2 hours and day 1, the distributions of Ag and Ab in the GBM were similar in immersion-fixed kidneys regardless of the preperfusion with phosphate-buffered saline. On the other hand, the passage of Ag across the lamina densa was delayed in the experimental rats as compared with the controls. Significant albuminuria also appeared on day 1. Despite the general concept that Ab binding to cationized Ag results in low avidity immune complex, cationized Ag translocated across the GBM in close association with Ab. The complement was activated biphasically in the subendothelial and in the subepithelial space. The subendothelial complement activation may have contributed to the translocation of immune complex. PMID- 8456944 TI - Co-localization of von Willebrand factor and type VI collagen in human vascular subendothelium. AB - The binding of von Willebrand factor (vWF) to subendothelium constitutes an important initial step in the process of platelet adhesion to exposed subendothelium following blood vessel injury. We previously demonstrated that vWF is present in human vascular subendothelium and recently found that a 150 kd vWF binding protein, which we extracted from subendothelium, is type VI collagen. Although we have established that vWF and type VI collagen bind in vitro, it is not known whether these two proteins are associated in the vascular subendothelium in situ. We, therefore, 1) investigated the morphological effects of our biochemical extraction procedure on human umbilical veins by scanning and transmission electron microscopy, 2) analyzed the subendothelial extract by immunofluorescence for the presence of vWF and collagens and by electron microscopy for morphological characteristics, and 3) localized vWF and type VI collagen in subendothelium by immunofluorescence and by single- and double-label immunoelectron microscopic studies with protein A-conjugated gold particles. We found that the surface exposed following de-endothelialization is composed of microfibrils and contains very little fibrillar collagen. The subendothelium is stripped after sodium dodecyl sulfate-urea extraction, and the extract itself contains immunoreactive vWF and type VI collagen but no immunoreactive type I or III fibrillar collagens. Immunofluorescence and immunoelectron microscopic studies showed that vWF and type VI collagen are both present in subendothelium, where both co-localized to microfibrils. In conclusion, vWF that binds to type VI collagen in vitro, also co-localizes with type VI collagen in subendothelium, where both are associated with microfibrils. Type VI collagen, therefore appears to serve as a biologically significant binding site for vWF in vivo and may thereby play a role in mediating platelet adhesion to exposed subendothelium following vascular injury. PMID- 8456945 TI - Tumor necrosis factor-alpha induces cell type and tissue-specific expression of chemoattractant cytokines in vivo. AB - Recombinant murine tumor necrosis factor-alpha (TNF-alpha) was shown to be a strong, systemic stimulus in vivo for members of the chemoattractant cytokine gene families (JE, KC, IP-10). The three genes showed differential sensitivity to TNF-alpha, and their expression demonstrated differential tissue specificity. IP 10 was the most strongly induced messenger RNA and was seen in the liver, kidney, and spleen but very poorly in the lung or skin. JE exhibited a similar pattern, though the magnitude of expression was markedly lower. KC expression was seen only in the liver of TNF-alpha-treated mice. The time course of expression for IP 10 was rapid and transient and showed strong dose dependence. In mice treated with TNF-alpha intravenously, messenger RNA was localized in the splenic stroma but not in adherent macrophages or nonadherent lymphocytes. In situ hybridization found the majority of intercrime expression in the splenic red pulp with little or no expression seen in the white pulp. In vitro, TNF-alpha was a potent stimulus of chemoattractant messenger RNA expression in fibroblasts but not in inflammatory peritoneal macrophages. These results indicate that TNF-alpha may be an important stimulus for chemoattractant cytokine gene expression in vivo, and the primary cell types responsible may be either stromal fibroblasts, microvascular endothelium, and/or a subset of anchored mononuclear phagocytes. PMID- 8456946 TI - An antibody against phosphorylated neurofilaments identifies a subset of damaged association axons in Alzheimer's disease. AB - We studied axonal damage in Alzheimer's disease frontal cortex and hippocampus with a novel monoclonal antibody (SMI 312) against phosphorylated neurofilaments. This antibody immunolabeled, with great detail, the neuropil axonal network. In aged normal cases only a few pyramidal cell perikarya were immunostained. In Alzheimer's disease there was a two- to four-fold increase in neuronal SMI 312 immunolabeling, and neuropil neuritic processes were severely disrupted. Double immunolabeling analysis showed that 88% of SMI 312-immunolabeled abnormal neuritic clusters were associated with amyloid, whereas the remaining 12% were not. Serial section analysis and 3-D reconstructions suggested that dystrophic neurites of classical plaques were derived from long axons. These abnormal neurites were also growth-associated protein 43 positive and occasionally tau positive. The present study supports the contention that a subpopulation of aberrantly sprouting axons in the neuritic plaque is derived from cortico-cortico fibers. This disruption of the neocortical association fibers and neuritic microcircuitry could underlie the cognitive impairment of Alzheimer's disease. PMID- 8456947 TI - Co-expression of low molecular weight neurofilament protein and glial fibrillary acidic protein in established human glioma cell lines. AB - This report describes the expression of glial and neuronal cytoskeletal proteins and their messenger RNAs (mRNAs) in established cell lines derived from human primitive neuroectodermal tumors (PNETs) and malignant gliomas. Northern blot analyses revealed neurofilament (NF) protein mRNAs in 6 of 7 PNET cell lines but no glial fibrillary acidic protein (GFAP) mRNA. Six of these cell lines contained mRNA for the microtubule-associated protein (MAP) known as MAP1b, whereas MAP2 mRNAs were detected only in 1 of the PNET cell lines. These findings closely paralleled previously published data on the expression of these cytoskeletal proteins in the same group of PNET cell lines. Although GFAP mRNA was detected in only 2 of 5 glioma cell lines, 4 of these cell lines contained mRNAs for the low molecular-weight (M(r)) NF protein (NF-L). Western blot analysis confirmed the expression of both GFAP and NF-L protein in 2 of the glioma cell lines (U251 MG and U373 MG) that contained GFAP and NF-L mRNAs. Further, double immunofluorescence studies showed that GFAP and NF-L co-localized in the same glioma cells. In contrast, neither the middle- (NF-M) or high- (NF-H) M(r) NF proteins or their mRNAs were detected in any of these glioma cell lines. Finally, MAP1b mRNA was expressed in all 5 glioma cell lines, whereas MAP2 mRNAs were detected in only 3 of the cell lines. This is the first documentation of the expression of both glial-specific and neuron-specific cytoskeletal proteins in human malignant glioma-derived cell lines. These data may reflect the aberrant induction of neuron-specific gene products in some neoplastic glial cell lines. Alternatively, our findings may indicate that some glioma cell lines correspond to transformed bipotential human central nervous system precursors of cells restricted to a neuronal or glial lineage. PMID- 8456948 TI - c-fos oncogene underexpression in salivary gland tumors as measured by in situ hybridization. AB - Tissue from 35 salivary gland tumors and 14 normal salivary glands was analyzed by in situ hybridization and computer-assisted morphometry for the expression of the c-fos oncogene. The normal salivary gland tissues were found to express c-fos focally, mainly in the acinar secretory cells. The majority of the cells in the normal tissues showed a high level of expression (47.74 +/- 5.31% of cells had 46 to 60 grains per cell and another 45.79 +/- 2.18% showed > 60 grains per cell). All the tumors examined exhibited a relatively low, uniform distribution of c-fos expression. For example, in the poorly differentiated adenocarcinomas, 96.83 +/- 04% of the cells were found to have < 15 grains per cell. A general linear model for multivariate analysis showed a significant difference between the various tumor types and the normal salivary gland tissues (P = 0.0001). These data support the hypothesis that salivary gland tumors belong to a group of epithelial neoplasias in which the loss of cellular differentiation is linked with underexpression of the c-fos oncogene. PMID- 8456949 TI - Differentiated bronchiolar epithelium in alveolar ducts of rats exposed to ozone for 20 months. AB - The effects of exposure to 1.0 ppm of ozone for twenty months were studied in male Fischer 344 rats. Light microscopic, morphometric, and immunohistological approaches were used to determine the distribution and degree of differentiation of ciliated and nonciliated bronchiolar epithelial (Clara) cells lining alveolar ducts of the central acinus, a primary target of ozone-induced lung injury. Alveolar duct pathways extending beyond the level of the most proximal alveolar outpocketing of terminal bronchioles were isolated in longitudinal profile. The distance that ciliated and nonciliated bronchiolar epithelial (Clara) cells projected down each alveolar duct pathway was determined by placing concentric arcs radiating outward from a single reference point at the level of the first alveolar outpocketing. A high degree of heterogeneity in the magnitude of bronchiolar epithelial cell extension into alveolar ducts was noted for each isolation and animal. Age-matched control animals also demonstrated variation in the degree of bronchiolar epithelial cell extension down alveolar ducts. In animals exposed to ozone, a striking similarity was noted by scanning electron microscopy in the surface characteristics of cells lining both terminal bronchioles and alveolar ducts. The presence of Clara cell secretory protein in cells of bronchioles and alveolar ducts was also detected immunohistochemically and visualized using confocal laser scanning microscopy in the reflectance mode. Well-differentiated ciliated and nonciliated bronchiolar epithelial cells were found lining alveolar septal tips and alveoli up to a depth of 1,000 mu into the pulmonary acinus after 20 months of exposure to ozone. No evidence of inflammation was present in alveolar ducts, suggesting that epithelial cell transformations in alveolar ducts is a natural consequence of lifetime exposures to oxidant gases. PMID- 8456950 TI - Animal model of human disease. Bovine beta-mannosidosis. PMID- 8456951 TI - Distribution and regulation of renal ecto-5'-nucleotidase: implications for physiological functions of adenosine. AB - Adenosine exerts various effects via membrane receptors in the kidney. It reduces the glomerular filtration rate by altering the resistance of the glomerular arterioles, and it inhibits the release of renin as well as neurotransmission. Adenosine receptors have been further found at different levels of the nephron as well as in glomerular cells. Little is known concerning the mechanisms that regulate the extracellular concentration of adenosine, namely, its production, transport, and catabolism. In the present review we first summarize the pathways of adenosine formation. Then we focus on the ecto-5'-nucleotidase, which seems to represent the major source of extracellular adenosine in the kidney; that enzyme is present in tubular luminal membranes, in fibroblasts, and in mesangial cells. In tubules the enzyme probably plays a role in the salvage of nucleotides present in the primary urine. The activity in fibroblasts is strategically located to convert any AMP released by tubules into adenosine in the close vicinity of glomerular arterioles, and it probably plays a predominant role in most of the regulatory mechanisms involving adenosine. Ecto-5'-nucleotidase activity in fibroblasts increases in anemia, maybe as a response to local hypoxia. PMID- 8456952 TI - Ammonium and bicarbonate transport in isolated perfused rodent long-loop thin descending limbs. AB - Ammonium accumulates in the renal medullas of antidiuretic mammals. The accumulation process is thought to involve countercurrent multiplication, energy dependent recycling between the ascending and descending limbs of Henle's loop. To investigate the role of the long-loop thin descending limb (LDL) in countercurrent multiplication of ammonium, we have perfused outer medullary and inner medullary subsegments of the chinchilla LDL (and inner medullary subsegments of rat LDL) in vitro and measured the fluxes of total ammonia and total CO2. No spontaneous fluxes of total ammonia or total CO2 occurred in the absence of imposed concentration gradients. When transepithelial concentration gradients were imposed, passive total ammonia and total CO2 transport were observed in all subsegments, although the permeabilities varied with distance along the descending limb. Passive total ammonia transport occurred through a combination of NH3 and direct NH4+ permeation. The outer medullary segment was the most permeable to NH4+. The deep inner medullary segment was the most permeable to bicarbonate. Addition of carbonic anhydrase to the lumen accelerated passive NH3 entry in the outer medullary LDL, indicating that little or no luminal carbonic anhydrase is endogenously present. The passive secretion of NH4+ and NH3 into the LDL may contribute to the countercurrent multiplication of ammonium in the rodent renal medulla. PMID- 8456953 TI - Model of ammonium and bicarbonate transport along LDL: implications for alkalinization of luminal fluid. AB - Luminal fluid exiting the proximal convoluted tubule of a juxtamedullary nephron is alkalinized as it passes through the long-loop thin descending limb of Henle (LDL). Three potential mechanisms of alkalinization are: 1) concentration of bicarbonate by water abstraction, 2) direct bicarbonate entry, and 3) NH3 entry. We have used a mathematical model of the LDL to investigate these mechanisms. With permeabilities of HCO3-, NH3, and NH4+ measured for subsegments of the chinchilla LDL [M. F. Flessner, R. Mejia, and M. A. Knepper. Am. J. Physiol. 264 (Renal Fluid Electrolyte Physiol. 33):F388-F396, 1993], the osmotic water permeability of each segment [C.-L. Chou and M. A. Knepper. Am. J. Physiol. 263 (Renal Fluid Electrolyte Physiol. 32):F417-F426, 1992], and appropriate parameters from the literature, we have used the model to calculate hypothetical pH, HCO3- concentration, and NH3 concentration of the luminal fluid as it descends the LDL within an assumed interstitium. After eliminating each mechanism in turn by setting the appropriate permeability to zero, we recalculated the axial profiles. Our results suggest that, although all three mechanisms individually contribute to LDL alkalinization, NH3 entry likely plays the dominant role. PMID- 8456954 TI - Role of renal interstitial hydrostatic pressure in natriuresis of systemic nitric oxide inhibition. AB - Systemic inhibition of nitric oxide synthesis with NG-monomethyl-L-arginine (L NMMA) increases renal perfusion pressure (RPP) and urinary sodium excretion. Increased RPP has been proposed as one of the mechanisms for the natriuresis caused by intravenous infusion of L-NMMA. We tested the hypothesis that increases in renal interstitial hydrostatic pressure (RIHP) are required for the natriuresis of L-NMMA infusion. Experiments were performed in four groups of Sprague-Dawley rats in which partial aortic clamping and/or bilateral renal decapsulation was performed to control RPP and RIHP. Infusion of L-NMMA (15 mg/kg bolus + 500 micrograms.kg-1 x min-1 continuous infusion) increased RPP (delta+ 14 +/- 1 mmHg), RIHP (delta+ 3.6 +/- 0.7 mmHg), and fractional excretion of sodium (FENa; delta 2.4 +/- 0.6%, P < 0.005). When RPP was prevented from increasing by controlling RPP with an adjustable clamp around the suprarenal aorta, RIHP and FENa did not significantly change. When only RIHP was held constant by bilateral renal decapsulation, FENa was not significantly increased (delta+ 0.68 +/- 0.36%, not significant), despite a significant rise in RPP (delta+ 18 +/- 2 mmHg, P < 0.001). Control of both RPP and RIHP prevented the increase in FENa. Thus, when renal interstitial pressure was controlled, the infusion of L-NMMA did not result in an increase in FENa. These results demonstrate that an increase in RIHP is a necessary component in the natriuresis due to systemic infusion of L-NMMA. PMID- 8456955 TI - Volume and agonist-induced regulation of myosin light-chain phosphorylation in glomerular mesangial cells. AB - We investigated whether cell volume decrease per se can activate intracellular mechanisms leading to mesangial cell contraction. For this purpose, we applied hyperosmotic stress to cultured glomerular mesangial cells and examined the effects on phosphorylation of myosin light chain (MLCP). Compared with control cells, hyperosmotic stress (390 mosmol/kg) attained by either NaCl or raffinose significantly increased MLCP to 140.7 +/- 7.0% (n = 5) and 134.8 +/- 7.7% (n = 4), respectively, in parallel with a decrease in the cell volume. This increase was comparable to that achieved by the following agonists: arginine vasopressin (AVP, 100 nM; n = 5) and endothelin-1 (ET, 10 nM; n = 5). By using two dimensional tryptic phosphopeptide mapping, contribution of myosin light-chain kinase (MLCK) and protein kinase C (PKC) to the observed phosphorylation was examined by identifying phosphorylation at serine-19 (by MLCK) and at serine-1 or serine-2 (by PKC). Under resting conditions, relative distribution of phosphorylation between MLCK and PKC sites was 60.1 +/- 8.4 and 39.9 +/- 8.4%. The relative contribution by these enzymes remained similar during hyperosmotic stress or agonist stimulation. Since cytosolic Ca2+ concentration ([Ca2+]i) is an important determinant of MLCP, we also examined [Ca2+]i in these settings. While AVP and ET-induced a characteristic transient spike in [Ca2+]i, hyperosmotic stress caused a gradual and modest increase in [Ca2+]i. These studies show that, in mesangial cells, reduction in cell volume induces MLCP through mechanisms distinct from those involved in agonist-induced events. PMID- 8456956 TI - Mechanisms of temporal variation in single-nephron blood flow in rats. AB - Modified laser-Doppler velocimetry was used to determine the number of different mechanisms regulating single-nephron blood flow. Two oscillations were identified in star vessel blood flow, one at 20-50 mHz and another at 100-200 mHz. Tubuloglomerular feedback (TGF) mediates the slower oscillation, and the faster one is probably myogenic in origin. Acute hypertension increased autospectral power in the 20-50 mHz and 100-200 mHz frequency bands to 282 +/- 50 and 248 +/- 64%, respectively, of control even though mean single-nephron blood flow was autoregulated. Mean blood flow increased 24.6 +/- 6.1% when TGF was inhibited by intratubular perfusion with furosemide, and it decreased 42.8 +/- 3.9% when TGF was saturated by tubular perfusion with artificial tubular fluid at high rates. Autospectral power in the low-frequency band decreased 50.5 +/- 9.6% during furosemide and decreased 74.9 +/- 5.9% during TGF saturation, consistent with a TGF origin of the slow oscillation. In contrast, autospectral power of the high frequency oscillation increased 75.4 +/- 23.9% during TGF inhibition and decreased 35.8 +/- 11% when TGF was saturated, suggesting interactions between the two spontaneously oscillating components in efferent arteriole blood flow. PMID- 8456957 TI - HCO3- transport in rat CCD: rapid adaptation by in vivo but not in vitro alkalosis. AB - Acute chloride-depletion alkalosis (CDA) in vivo results in sustained net total carbon dioxide (tCO2) secretion in vitro in the rat cortical collecting duct (CCD) for several hours. To determine whether altering in vitro pH and electrolytes similarly result in tCO2 secretion, CCD were incubated for 1 h at 37 degrees C in an alkalotic environment similar to in vivo arterial pH, PCO2, and electrolytes (pH 7.6, 40 mM HCO3). The in vitro alkalosis incubation had no effect on tCO2 transport. Second, alteration of the magnitude of vivo alkalosis was correlated with in vitro tCO2 transport. After generation of CDA by intraperitoneal dialysis against 154 mM HCO3-, rats received an infusion for 2.5 h of either 5% dextrose to maintain alkalosis or 154 mM NaCl at differing rates to partially correct or fully correct the systemic alkalosis. After in vitro isolation and perfusion, in vitro tCO2 flux correlated with in vivo Cl- balance (r2 = 0.82), serum HCO3- (r2 = 0.84), and arterial H+ concentration (r2 = 0.78), but not with K+ balance (r2 = 0.33). These findings suggest that: 1) the regulation of tCO2 transport in vitro correlates with the degree of systemic alkalosis and Cl- balance in vivo, and 2) simulating alkalotic pH and electrolytes in vitro does not rapidly alter transport as does in vivo CDA within a similar time. Taken together, pH and electrolyte changes alone cannot account for the rapid adaptation of tCO2 transport in the CCD, but an in vivo factor(s) contributes importantly to alter tCO2 transport in magnitude and direction that would tend to restore normal acid-base balance. PMID- 8456958 TI - Modulation of tubuloglomerular feedback responsiveness by extracellular ATP. AB - Experiments were performed in pentobarbital sodium-anesthetized rats to determine the effects of activation of P2 purinoceptors sensitive to ATP on glomerular capillary pressure, as estimated from proximal tubule stop-flow pressure (SFP) measurements, and on the magnitude of maximal tubuloglomerular feedback-mediated reductions in SFP. To selectively expose nephrons in vivo to ATP without influencing arterial blood pressure, we infused ATP directly into the surrounding peritubular capillaries. Peritubular capillary infusion, at a rate of 20 nl/min, of an isotonic saline solution containing 10(-3) M ATP elicited a transient decrease in resting SFP. However, subsequent infusion of 10(-3) M ATP together with the adenosine receptor (P1 purinoceptor) antagonist 1,3-dipropyl-8-p sulfophenylxanthine (PSPX, 10(-3) M) into the same vascular sites elicited a sustained decrease in resting SFP. Peritubular infusion of the slowly metabolizable ATP analogue, beta,gamma-methylene-ATP (10(-3) M), at a rate of 20 nl/min, also elicited a transient decrease in SFP, but this was not converted to a sustained response by PSPX. The SFP feedback responses to a late proximal perfusion rate of 40 nl/min were markedly attenuated during peritubular infusion of either 10(-3) M ATP (8.7 +/- 1.2 vs. 1.8 +/- 0.9 mmHg; P < 0.01, n = 9) or 10( 3) M beta,gamma-methylene-ATP (8.2 +/- 1.3 vs. 2.2 +/- 1.2 mmHg; P < 0.01, n = 8).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8456959 TI - Functional evidence for an apical V1 receptor in rabbit cortical collecting duct. AB - In the rabbit cortical collecting duct (CCD) perfused in vitro, we recently found that luminal arginine vasopressin (AVP) hyperpolarizes the transepithelial voltage (Vt) and inhibits the hydrosmotic effect of basolateral AVP. The present study was undertaken to characterize the apical receptor of the CCD for AVP. In contrast to AVP, luminal application of 1-desamino-8-D-arginine vasopressin (DDAVP), a V2 agonist, did not significantly induce hyperpolarization. Luminal oxytocin (OXT) hyperpolarized Vt, interfering with the effect of superimposed luminal AVP, whereas [Thr4,Gly7]OXT, an OXT agonist, did not reproduce the effect of OXT. The effects of luminal AVP and OXT were abolished by [d(CH2)5,Tyr(Me)] AVP, a V1 antagonist. Finally, luminal applications of AVP metabolite neuropeptides, pGlu-Asn-Cys(Cys)-Pro-Arg and pGlu-Asn-Cys(Cys)-Pro-Arg-Gly-NH2, were without effect on Vt. These data suggest that luminal AVP induces hyperpolarization through an apical V1 receptor but not through a V2 receptor or an OXT receptor. PMID- 8456960 TI - Determinants of relative amounts of medullary organic osmolytes: effects of NaCl and urea differ. AB - Sorbitol, inositol, betaine, taurine, and glycerophosphorylcholine (GPC) are organic osmolytes that accumulate in the renal inner medulla during antidiuresis. In the cultured cell model, high medium sodium increases all the cell osmolytes and high medium urea increases cell GPC and inositol. It has been difficult, however, to discriminate between the effects of sodium and urea on organic osmolytes in water-deprived animals. To determine the nature of the in vivo responses of osmolyte accumulation induced by extracellular sodium or urea, we measured the medullary organic osmolytes and tested the degree of their linear correlation with urine and tissue parameters in control, dehydrated, salt-loaded, and urea-loaded rats. All of the osmolytes except myo-inositol increased in salt loaded rats. Betaine and sorbitol contents in dehydrated rats were less than in salt-loaded rats, but other osmolytes increased significantly. Conversely, in urea-loaded rats, only GPC increased significantly, whereas either no change occurred for other osmolytes or sometimes betaine and sorbitol levels decreased. These data suggest that high sodium increases all of the osmolytes except myoinositol, whereas high urea increases only GPC and may decrease the renal medullary contents of betaine and sorbitol. We also demonstrated, using linear regression analysis, that urea and electrolyte in urine as well as tissue correlate well with each osmolyte measured. PMID- 8456961 TI - ANP kinetics in normal men: in vivo measurement by a tracer method and correlation with sodium intake. AB - 125I-labeled atrial natriuretic peptide (ANP) was bolus injected into seven healthy human male subjects on an unrestricted diet (sodium intake ranging from 80 to 300 mmol/day). A high-performance liquid chromatographic procedure was used to purify the labeled hormone and the principal labeled metabolites in venous plasma samples collected up to 50 min after injection. The main ANP kinetic parameters were derived from the disappearance curves of the 125I-ANP, which were satisfactorily fitted by a biexponential function in all subjects. Newly produced ANP initially distributes in a large space (plasma-equivalent volume is 12.1 +/- 3.6 l/m2 body surface); the hormone rapidly leaves this sampling space through both degradation and distribution in peripheral spaces, as indicated by the single-pass mean transit time through the sampling space (3.9 +/- 1.2 min). The mean residence time in the body (22.7 +/- 23.1 min) and the plasma-equivalent total distribution volume (30.9 +/- 12.0 l/m2) indicate that ANP is also widely distributed outside the initial space. Metabolic clearance rate (MCR) values were distributed across a wide range (from 740 to 2,581 ml.min-1 x m-2) and were shown to correlate strongly with the daily urinary excretion of sodium. These results indicate that: 1) newly produced ANP is rapidly distributed and degraded, 2) the body pool of the hormone can be considered as a combination of two exchanging spaces, 3) circulating ANP is < or = 1/15 of the body pool, and 4) MCR of ANP is closely related to sodium intake, at least in normal subjects on a free sodium intake diet. PMID- 8456962 TI - Regulation of basolateral K channels in proximal tubule studied during continuous microperfusion. AB - Potassium channel activity of the basolateral membrane of the collagenase-treated rabbit proximal convoluted tubule (PCT) was studied during continuous luminal microperfusion. In cell-attached patches (high-K pipette) an inwardly rectifying potassium channel was observed with an inward slope conductance of 60.8 +/- 3.3 pS (n = 12) and outward slope conductance of 17.1 +/- 2.7 pS (n = 6). Stimulation of transcellular sodium transport with luminal glucose and alanine increased channel activity [measured as single-channel open probability (NPo)] from 0.19 +/ 0.11 to 0.44 +/- 0.09 (n = 8). This increase in channel activity was not likely to be mediated by either cell depolarization or cell swelling, because channel activity was voltage insensitive over physiological potentials and because the channel was not activated by stretch. However, channel activity was pH sensitive; reducing luminal pH from 7.4 to 6.5 reduced NPo from 0.63 +/- 0.24 to 0.26 +/- 0.16 (n = 5). Our work demonstrates the feasibility of patch clamping the basolateral membrane of microperfused nephron segments. This has allowed us to follow the activity of this potassium channel during an increase in sodium transport and show that its activity does increase during this maneuver. We conclude that: 1) it is possible to patch clamp the basolateral membrane of microperfused nephron segments, and 2) basolateral membrane of the rabbit PCT contains an inwardly rectifying, pH-sensitive potassium channel. The behavior of this channel on stimulation of transcellular sodium transport could explain the macroscopic increase in basolateral potassium conductance observed under similar conditions. PMID- 8456963 TI - Role of tissue renin angiotensin system in two-kidney, one-clip hypertensive rats. AB - To investigate the molecular pathology of two-kidney, one-clip (2K-1C) rats, we examined the gene expressions of the renin-angiotensin system (RAS) and angiotensin II (ANG II) concentration in various tissues in the early (4 wk) and chronic (16 wk) phases of hypertension. Four weeks after clipping, the brain renin mRNA level was lower in 2K-1C rats than in control rats (P < 0.05). On the other hand, the levels of brain and renal angiotensinogen mRNA were not significantly different in the two groups. The brain and adrenal ANG II concentrations were significantly higher in 2K-1C rats than in control rats. Sixteen weeks after clipping, there was no significant difference in the brain renin mRNA levels in the two groups, and renal and brain angiotensinogen mRNA levels were normal. Moreover, the ANG II concentrations in the adrenals and brain (except the cortex) of 2K-1C rats were not significantly higher than those in control rats. These results show a differential pattern of tissue RAS gene expression in rats during the development of 2K-1C hypertension, which is regulated in a tissue-specific manner. Furthermore, the data suggest that brain ANG II may be affected by circulating ANG II, but not by the brain renin angiotensin system, and may regulate brain renin, probably by negative feedback through its own receptor. PMID- 8456964 TI - Increased soluble EGF after ischemia is accompanied by a decrease in membrane associated precursors. AB - We have characterized the distribution of immunoreactive epidermal growth factor (irEGF) in control and ischemia-injured rat kidneys. Kidneys that had undergone ischemic injury contained levels of soluble irEGF that were six times those of uninjured kidneys. The predominant forms of soluble irEGF were native and des-Arg epidermal growth factor (EGF), both of which are biologically active. Crude membrane fractions from whole kidneys were solubilized in Triton X-100 and tested for irEGF. Amounts of irEGF were slightly decreased in the ischemia-injured kidney membranes. However, when solubilized membrane fractions were digested with trypsin, which generates a single immunoreactive species which appears identical to native EGF, the amount of irEGF in control fractions increased 13-fold and the amount in injured fractions increased only 4-fold as measured by radioimmunoassay. To better characterize the membrane-associated irEGF, Triton X 100-solubilized membrane fractions from control animals were affinity purified and subjected to high-performance liquid molecular sieve chromatography. Three major peaks of material exhibited immunoreactivity to EGF antibodies, bound the EGF receptor, and stimulated [3H]thymidine incorporation in growth-arrested fibroblasts. Trypsin digestion of the two high-molecular-mass peaks enhanced these activities. The third peak eluted with native EGF and showed no change in activity with trypsin addition. We propose that EGF is released from membrane associated EGF precursors and can then act in an autocrine or paracrine fashion to promote cell growth after ischemia-induced acute renal failure. PMID- 8456966 TI - The Robert W. Berliner Award for excellence in renal physiology. PMID- 8456965 TI - Rat kidney band 3 Cl-/HCO3- exchanger mRNA is transcribed from an alternative promoter. AB - We have previously shown that the rat kidney band 3 Cl-/HCO3- exchanger mRNA encodes an NH2-terminal truncated form of band 3 and that its 5' end differs from that of the erythrocyte band 3 mRNA (K. E. Kudrycki and G. E. Shull. J. Biol. Chem. 264: 8185-8192, 1989). To determine the genetic basis for the alternative kidney and erythroid mRNAs, we 1) isolated and characterized a rat erythroid band 3 cDNA, 2) isolated the rat band 3 gene and determined the exon/intron organization of sequences corresponding to the alternative 5' ends of the rat kidney and erythroid mRNAs, and 3) identified the transcription initiation sites of the two transcripts. The unique sequences at the 5' end of the rat erythroid mRNA are derived from exons 1-3 and are followed directly by sequences from exon 4 that are common to both mRNAs. In the kidney mRNA, sequences upstream of exon 4 are derived entirely from intron 3. Primer extension and S1 nuclease protection analyses demonstrate the presence of multiple transcription initiation sites for the rat erythroid band 3 mRNA at the beginning of exon 1, whereas the transcription initiation site for the kidney mRNA is located within intron 3. Thus two distinct promoters, separated by almost 5 kb of genomic sequence, are responsible for the highly tissue-specific transcription of the alternative rat erythroid and kidney band 3 mRNAs. PMID- 8456967 TI - A reappraisal of ventricular fibrillation threshold testing. AB - To test the hypothesis that ventricular fibrillation (VF) threshold testing is a probability function, 12 open-chest dogs were studied. The VF thresholds were tested by scanning the T wave with either the single premature stimulus method or with the train stimulus method. The dose-response curve method was used to determine the probability of inducing VF with different strengths of premature stimulation. Conventional methods and up-down methods were also used to test the VF threshold. The results showed that the VF threshold is a probability function. The conventional method VF threshold for the single premature stimulus and for the train stimulus methods corresponded to the current strength associated with a 23.4 +/- 13.2 and a 33.2 +/- 19.5% probability of VF (P < 0.05), respectively. In comparison, the triplicate VF threshold determined by the up-down algorithm method resulted in values that were not significantly different from a 50% probability of inducing VF, with a good correlation (r = 0.90, P < 0.001 for single and r = 0.89, P = 0.003 for the train stimulus method). We conclude that: 1) The VF threshold is a probability function, and 2) the triplicate VF threshold determined by the up-down algorithm method is the best alternative to the dose response curve method in estimating 50% probability of inducing VF. PMID- 8456968 TI - Determination of left atrial volume using sonomicrometry: a cast validation study. AB - We developed a technique for left atrial (LA) volume estimation using two pairs of sonomicrometers sewn to the anteroposterior (LAX) and mediolateral (SAX) LA diameters and validated the method against water displacement of LA casts in 15 dogs. LA pressure was adjusted to a preselected level (5, 10, or 15 mmHg) by dextran infusion and was matched by postmortem infusion of casting resin (Conthane DPEN-18402). LA volume was modeled empirically as an ellipsoid of revolution without regression constants [(SAX)2(LAX)]. There was a strong correlation between the calculated LA volume and water displacement of the LA body [r = 0.87, standard error of estimate (SEE) = 3.3 ml, P = 0.0001] but a weaker correlation against water displacement of the entire LA (body+appendage, r = 0.81, SEE = 3.9 ml, P = 0.0003). The appendage volume fraction (appendage volume/total LA volume), as determined by water displacement of the casts, increased with increasing LA size (r = 0.78, P = 0.001). These data indicate that, in the normal canine heart, LA volume can be estimated accurately with high temporal and spatial resolution sonomicrometry using two atrial dimensions, and the contribution of appendage to total LA volume may become significant as the atrium enlarges. PMID- 8456969 TI - Cardiac functional responses to adenosine by PD 81,723, an allosteric enhancer of the adenosine A1 receptor. AB - Adenosine, a locally released and rapidly metabolized nucleoside, protects the heart from damage during ischemia by reducing oxygen demand and increasing oxygen supply. The aminothiophene derivative (2-amino-4,5-dimethylthien-3-yl)[3 (trifluoromethyl)phenyl]-met hanone (PD 81,723) has been shown to act as an allosteric enhancer of the adenosine A1 receptor in brain membranes and thyroid cells. The present study investigates the effects of PD 81,723 in spontaneously contracting right atria and electrically stimulated left atria isolated from Sprague-Dawley rats. N6-cyclopentyladenosine (CPA), an adenosine A1 receptor agonist, produced concentration-dependent inhibition of heart rate in right atria and contractile parameters in left atria. In the right atrium, 5 microM of PD 81,723 significantly shifted the concentration-response curves for CPA to the left, both in the absence and presence of a nonselective adenosine receptor antagonist, 8-(p-sulfophenyl)theophylline (8-SPT, 10 microM). In the left atrium, PD 81,723 also shifted the concentration-response curves for CPA to the left, but only in the presence of 8-SPT. Potentiation of CPA-induced negative chronotropic and inotropic responses with PD 81,723, although not significant, was also observed in the presence of a selective adenosine A1 receptor antagonist, 1,3 dipropyl-8-cyclopentylxanthine (DPCPX, 1 nM). These results demonstrate that PD 81,723 enhances the direct negative chronotropic and inotropic effects of adenosine A1 receptor activation in rat atria. PMID- 8456970 TI - Age-related changes in endothelial permeability and distribution volume of albumin in rat aorta. AB - Age-related changes in macromolecular transport across the arterial wall were investigated in 10-, 20-, and 30-mo-old WAG/Rij rats. Animals were injected with 125I- and 131I-labeled albumin, 90 and 5 min before they were killed, respectively. The transmural distribution of relative concentration of tracers in the aortic wall was obtained using en face serial sectioning technique. The apparent endothelial permeability to albumin calculated from the distribution of 5-min 131I-labeled albumin concentrations was significantly enhanced in 20- and 30-mo-old rats compared with 10-mo-old rats. The apparent distribution volume of albumin within the media, estimated as the mean medial 125I-labeled albumin concentration, was not significantly changed in 20-mo-old rats but was significantly decreased in the 30-mo-old animals. These age-related changes in the macromolecular transport suggest that the entry of plasma macromolecules in the aged arterial wall might be enhanced, whereas the efflux through the media may be impeded, possibly contributing to their trapping in the subendothelium. PMID- 8456971 TI - Effects of chronic heart failure on skeletal muscle vascular transport capacity of rats. AB - The purpose of this study was to determine the effects of chronic heart failure (HF) on the vascular transport capacity of rat skeletal muscle. A large myocardial infarction (MI) was surgically produced in rats by ligating the left main coronary artery (n = 10). Sham operations were performed in control animals (Sham, n = 4). The vascular transport capacity of each animal's hindquarters was determined 8-9 mo post-MI to ensure that each rat was in a chronic state of left ventricular (LV) dysfunction and HF. With the use of an isolated, maximally vasodilated hindquarters preparation, we found that perfusion pressures, capillary pressures, capillary filtration coefficients, and precapillary vascular resistances were similar for the two groups under isogravimetric conditions. In contrast, postcapillary resistance was elevated (Sham, 0.9 +/- 0.2; MI, 1.5 +/- 0.2 mmHg.ml-1 x min x 100 g; P = 0.03), and flow to the hindquarters was reduced for rats in chronic HF compared with controls (Sham, 16.1 +/- 2.3; MI, 12.1 +/- 0.9 ml.min-1 x 100 g-1; P = 0.07). Vascular flow capacity (VFC) for the hindquarters was similar for control rats and rats with chronic HF across a wide range of perfusion pressures (20-60 mmHg). However, regional flow capacities were reduced in soleus and red gastrocnemius but not in white gastrocnemius muscles of rats in chronic HF compared with controls. These results suggest that the VFC of muscle comprised primarily of high oxidative fibers is selectively reduced in rats with chronic HF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8456972 TI - Formation and salvage of adenosine by macrovascular endothelial cells. AB - Contribution of extracellular adenine nucleotide degradation to adenosine formation and internal salvage of adenosine via adenosine kinase were quantified in macrovascular porcine endothelial cells. Microcarrier beads covered with endothelial cells were kept in a perfusion column at a flow rate of 2 ml/min. Total adenine nucleotide (AN) release was quantified with a sensitive firefly luciferin-luciferase assay after enzymatic rephosphorylation of AMP and ADP to ATP. Adenosine (ADO) was measured by radioimmunoassay or high-pressure liquid chromatography (HPLC) techniques. Basal AN and ADO release under steady-state conditions were 2.2 and 13.8 pmol.min-1 x ml column volume (CV)-1, respectively. Inhibition of adenosine deaminase with erythro-9-(2-hydroxy-3-nonyl)adenine (5 x 10(-6) M) enhanced ADO release by 3.3 pmol.min-1 x ml CV-1, and AN release remained unchanged (2.8 pmol.min-1 x ml CV-1). Inhibition of adenosine kinase by 5-iodotubercidine (10(-5) M) greatly enhanced ADO release by 97.7 pmol.min-1 x ml CV-1, while AN release was unaffected. Inhibition of ecto-5'-nucleotidase by alpha,beta-methylene-ADP (5 x 10(-5) M) enhanced AN release from 2.6 to 8.2 pmol.min-1 x ml CV-1 and reduced ADO release by an equivalent extent. Stimulation of endothelial cells with Ca ionophore A23187 dose dependently augmented AN and ADO release to 2,013.2 and 92.5 pmol.min-1 x ml CV-1, respectively. Thrombin (1 U/ml) enhanced AN release from 5.0 to 8.7 pmol.min-1 x ml CV-1, whereas several other endothelium-dependent and -independent vasodilators including acetylcholine, bradykinin, isoproterenol, and norepinephrine were proven to have no significant effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8456973 TI - Competition between palmitate and ketone bodies as fuels for the heart: study with positron emission tomography. AB - To test the ability of ketone bodies to inhibit myocardial fatty acid oxidation in vivo, the myocardial clearance kinetics of [1-11C]palmitate was assessed with positron emission tomography in six fasted volunteers and six instrumented dogs, studied repeatedly before and during infusion of 3-hydroxybutyrate (17 mumol.kg-1 x min-1). With the use of multiexponential fitting of tissue time-activity curves, the size, half time (T1/2), and index of the early rapid phase of 11C myocardial clearance, reflecting palmitate oxidation, were calculated. In humans, the relative size (-28%, P < 0.001) and index (-37%, P < 0.01) of the early rapid phase decreased significantly during infusion of 3-hydroxybutyrate, consistent with decreased fatty acid oxidation. Paradoxically, T1/2 decreased from 10.1 +/- 1.6 to 7.4 +/- 1.1 min (P < 0.01). To elucidate possible mechanisms, multiple coronary arteriovenous samples were obtained from the dogs to assess the efflux of oxidized and nonmetabolized tracer. Infusion of 3-hydroxybutyrate resulted in decreased myocardial [11C]CO2 production (-40%, P < 0.05) and reduced palmitate retention (-38%, P < 0.05). In three dogs, the arteriovenous difference in radiolabeled palmitate became negative 10 min after injection, indicating backdiffusion of nonmetabolized tracer from the myocardium. Thus a steady-state infusion of 3-hydroxybutyrate, resulting in physiological plasma levels, alters [1-11C]palmitate kinetics in vivo by decreasing myocardial long-chain fatty acid oxidation and by increasing backdiffusion of nonmetabolized tracer. PMID- 8456974 TI - Coronary arterial inflow impediment during systole is little affected by capacitive effects. AB - During cardiac contraction coronary arterial inflow is impeded, whereas venous flow is augmented. These effects are assumed to be caused by diameter reductions of intramyocardial blood vessels. The reduction in vascular diameter (and thus vascular volume) during contraction increases coronary resistance and/or decreases back pressure so that flow decreases and the rate of change of volume results in a capacitive flow. The aim of this study was to estimate the contribution of capacitive flow to total coronary inflow impediment. Isolated blood-perfused (100 mmHg and constant), maximally vasodilated, ryanodine pretreated rat hearts (n = 8) with intraventricular balloons were used. The coronary inflow impediment during isovolumic beats at a heart rate of 2-3 Hz (dynamic contractions) and during prolonged systoles obtained by fast pacing (static contractions, no capacitive flow impediment) were compared. Changing left ventricular balloon volume enabled us to vary left ventricular pressure and to relate systolic flow to systolic left ventricular pressure. We found that for the same contractility (expressed in terms of systolic pressure-volume relationship and maximal elastance) and same left ventricular pressure, the ratio of coronary inflow impediment in dynamic and static contractions is not significantly different from unity (P < 0.005). This implies that under our experimental conditions coronary inflow impediment in dynamic contractions is little affected by capacitive effects. PMID- 8456975 TI - Lysophosphatidylcholine modifies G protein-dependent signaling in porcine endothelial cells. AB - Certain endothelial receptors are coupled to a pertussis toxin-sensitive inhibitory guanine nucleotide-binding regulatory (Gi) protein. In pigs, hypercholesterolemia causes a selective impairment of this Gi protein-dependent pathway. Recent studies have suggested that hypercholesterolemia-induced endothelial dysfunction may be caused by lysophosphatidylcholine (LPC) derived from oxidized low-density lipoprotein (LDL). The aim of the present study was to determine whether LPC could inhibit the Gi protein-dependent pathway. Isolated rings of porcine coronary arteries were suspended for isometric tension recording in organ chambers filled with physiological salt solution (37 degrees C, 95% O2 5% CO2). In rings with endothelium contracted with prostaglandin F2 alpha, pertussis toxin (100 ng/ml) or LPC (10(-5) M) inhibited the endothelium-dependent relaxations evoked by UK-14,304, an alpha 2-adrenergic agonist, or by serotonin, but not those caused by bradykinin or ADP. LPC also did not inhibit relaxations produced by SIN 1, an endothelium-derived relaxing factor-nitric oxide donor. After treatment of the rings with pertussis toxin, LPC no longer inhibited the endothelium-dependent relaxations to serotonin. Although LPC inhibited the responses of membrane-bound receptors that activate the pertussis toxin-sensitive Gi protein, LPC did not affect the endothelium-dependent relaxations evoked by direct activation of the pertussis toxin-sensitive Gi protein by fluoride. These results suggest that LPC selectively inhibits a Gi protein-dependent pathway in porcine endothelial cells possibly by disrupting receptor-G protein interactions. LPC that is associated with oxidized LDL may mediate in part the dysfunction in the endothelial Gi protein-dependent pathway associated with hypercholesterolemia. PMID- 8456976 TI - Impaired early and intact late diastolic function in stunned myocardium induced by demand ischemia. AB - Changes in left ventricular diastolic properties of pacing-induced stunned myocardium were examined in 10 anesthetized dogs instrumented with a micromanometer for left ventricular pressure and sonomicrometers for left ventricular short axis, anterior and posterior segment lengths, and posterior wall thickness. After the creation of a critical stenosis on a carotid-circumflex coronary artery bypass, left ventricular pressure and dimensions were recorded simultaneously during temporary superior and inferior vena caval occlusion to allow for the construction of end-diastolic pressure-segment length curves. After 15 min of high-frequency pacing (190-220 beats/min), measurements were repeated and compared with those before pacing. The mean lengthening rate of each dimension during the first half of diastole was calculated as an index of early diastolic function. Three minutes after the end of pacing, coronary blood flow and perfusion pressure were unchanged, whereas systolic function of the posterior wall was depressed, indicating stunning of the posterior myocardium. The time constant of left ventricular pressure decay was prolonged by 14%. The mean lengthening rate during the first half of diastole decreased by 50% in the left ventricular internal short axis and by 119% in the posterior segment. Despite the significant impairment of early diastolic function, the regional end-diastolic pressure-segment length relation of the posterior wall was unchanged. Thus, in contrast to the results reported for pacing-induced ischemia that were measured immediately after pacing, the distensibility of the left ventricular wall in stunned myocardium induced by pacing was unchanged despite depressed early diastolic function. PMID- 8456977 TI - Circulatory models in assessment of cardiac enzyme release in dogs. AB - Cardiac ischemia causes interstitial leakage of cellular enzymes followed by release of these enzymes into plasma. Quantitative interpretation of these data requires a specific circulatory model, and the performance of such models was investigated. Plasma activities of cardiac enzymes were measured for increasingly abrupt forms of ischemic heart injury in the dog: 1) permanent ligation of the left anterior descending coronary artery (LAD); 2) reperfusion after 2 h of ligation of the LAD; and 3) calcium-free perfusion of the LAD during 10 min (calcium-paradox injury). Release into plasma of a rapidly (41%/h) and a slowly (2.2%/h) catabolized enzyme was calculated from the plasma activities, using a detailed circulatory model with compartments for heart, plasma, muscle, skin, and viscera. The time course of cellular enzyme leakage into interstitial space in the heart was calculated from release into plasma and a range of reported values for transendothelial permeability. Simplification to one- and two-compartment models introduced, respectively, 10 and 2% error in calculated cumulative release. Considering the other sources of error, this implies adequate performance of the two-compartment model. Protein washout from the heart is strongly influenced by expansion of interstitial protein space with dead myocyte volume and depends on the microheterogeneity of necrotic tissue areas. Accelerated release of enzymes into plasma after reperfusion reflects accelerated cellular leakage rather than enhanced washout. PMID- 8456978 TI - Heart rate perturbation in the stage 17-27 chick embryo: effect on stroke volume and aortic flow. AB - Heart rate (HR), stroke volume (SV), and aortic flow increase linearly between developmental stages 17 and 27, as the embryonic chick heart progresses from a bent tube to a rudimentary four-chambered structure and cardiac mass increases fourfold. We hypothesized that HR perturbation, expressed as percent of intrinsic HR (%HR), would have a developmentally dependent effect on flow and SV. HR was transiently perturbed to 40-250% of intrinsic rate with a 1-mm cooled or heated steel probe applied to the sinus venosus of 81 embryos. Aortic blood velocity, cross-sectional area, and HR were used to calculate flow and SV. At each stage, flow was maximal at intrinsic HR. The %HR vs. SV relationship was linear, inverse, and developmentally dependent. In spite of a tremendous change in ventricular shape, mass, and volume, HR control during development of the preinnervated heart maximizes blood flow to the developing embryo. PMID- 8456979 TI - ANG II receptors, c-myc, and c-jun in myocytes after myocardial infarction and ventricular failure. AB - To determine the relationship between reactive cardiac hypertrophy and the expression of angiotensin II (ANG II) receptors in surviving myocytes after infarction, large infarcts were produced in rats that were killed 2-3 days later. Measurements of global ventricular dynamics indicated that left ventricular failure and right ventricular dysfunction occurred in experimental animals. These alterations in ventricular pump function were associated with increases in ventricular weight-to-body weight ratio, indicative of developing cardiac hypertrophy. Such a response was coupled with a 6.6-fold increase in ANG II receptor mRNA in myocytes from the left ventricle. A 2.3-fold increase in the expression of ANG II receptor in myocytes from the right ventricle was also found. Radioligand binding assay documented a 44% increase in the density of ANG II receptors on left ventricular myocytes of infarcted hearts. To establish whether the induction of genes commonly associated with myocyte hypertrophy was present, the message for c-myc and c-jun was biventricularly assessed. Myocardial infarction was accompanied by overexpressions of c-myc and c-jun that were more prominent in left than in right ventricular myocytes. In conclusion, the enhanced expression of ANG II receptor and its receptor protein and c-myc and c-jun in myocytes may participate in the reactive growth processes of these cells after infarction. PMID- 8456980 TI - Functional distribution of coronary vascular volume in beating goat hearts. AB - With use of hemoglobin-bound O2 as an endogenous tracer, intramyocardial blood volume distribution between vessels involved in O2 exchange and more distal vessels was estimated. In nine anesthetized open-chest goats, the left main coronary artery was cannulated and perfused at a constant flow. Coronary arteriovenous O2 content difference (AVOX) was measured. AVOX transients induced by a flow step could be characterized by two phases: delay time and slow change to a new steady state. AVOX responses were fitted by a two-compartment model consisting of a well-mixed compartment from which O2 is consumed with volume Vm, and a distal unmixed compartment without O2 exchange, with volume Vunm. The rate of change of the AVOX transient depends on Vm, whereas the delay time depends on Vunm. Measurements in nine goats resulted in a Vm value of 9.9 +/- 1.1 (SE) ml/100 g (n = 9) and a Vunm value of 3.8 +/- 0.3 ml/100 g. Maximal vasodilation caused a significant increase in Vm (13.1 +/- 1.3 ml/100 g; n = 5), whereas Vunm did not change (5.0 +/- 0.5 ml/100 g). Hence, the increase of intramyocardial blood volume induced by vasodilation must be expected in the capillary bed and not in the coronary veins. PMID- 8456981 TI - Cardiopulmonary and carotid baroreflex control of splanchnic and forearm circulations. AB - The objective was to determine whether a rise in carotid sinus transmural pressure by neck suction (NS) would counteract vasoconstriction secondary to inhibition of discharge of arterial and cardiopulmonary baroreceptors by simultaneous lower body negative pressure (LBNP). NS alone was applied to seven normal human subjects at -40 mmHg for 400-600 ms at each heartbeat during a 6-min period. NS reduced mean arterial pressure (MAP) from 94 +/- 6 to 86 +/- 9 mmHg and heart rate (HR) from 64 +/- 5 to 60 +/- 4.7 beats/min but did not affect vascular resistance in the splanchnic region (flow by constant infusion of indocyanine green; assumed constant extraction) or in the forearm (venous occlusion plethysmography). The same NS stimulus was applied during 23 min of continuous LBNP at -40 mmHg. LBNP alone before NS significantly reduced central venous pressure (CVP) from 5 +/- 0.3 to 1 +/- 0.5 mmHg and raised splanchnic (+34%) and forearm (+70%) vascular resistances and HR (from 64 to 74 beats/min) without reducing MAP. NS plus LBNP reduced MAP from 103 +/- 8 to 95 +/- 6 mmHg and HR from 74 +/- 6 to 67 +/- 5 beats/min without changing CVP but did not alter vascular resistances, which remained elevated and constant throughout LBNP before and after NS. Increments in plasma concentrations of renin (240%), aldosterone (70%), epinephrine (112%), and norepinephrine (46%) accompanied LBNP and NS; a separate influence of NS was not discernible. We conclude that vasoconstriction in response to combined cardiopulmonary and aortic inhibition is not overpowered by carotid sinus stimulation. PMID- 8456982 TI - Mechanisms of antifibrillatory effect of acidic reperfusion: role of perfusate bicarbonate concentration. AB - Transient (2 min) acidic (pH 6.6) reperfusion with low [HCO3-] solution suppresses reperfusion-induced ventricular fibrillation (VF) in the isolated rat heart. Using this preparation, we tested whether the effect was mediated by the high [H+] or the low [HCO3-] of perfusate. Left and right coronary beds were independently perfused with HCO3(-)-containing (25.0 mmol/l) solution at pH 7.4. Regional ischemia was then induced by stopping flow to the left coronary bed for 10 min. Hearts were subsequently assigned to four groups (n = 12 hearts/group), and the left coronary bed was reperfused with either HCO3(-)-containing (25.0 or 4.0 mmol/l) or HCO3(-)-free (5.0 mmol/l HEPES) solution, at pH 7.4 throughout (control reperfusion) or at pH 6.6 for the first 2 min and at pH 7.4 from 2 to 5 min (acidic reperfusion). Regardless of the buffer, controls exhibited a high (92 and 100%) incidence of VF; this was reduced to 42% in both of the acidic reperfusion groups (P < 0.05). There were no intergroup differences in heart rate, coronary flow, or size of ischemic zone. Thus high [H+], rather than low [HCO3-], appears to mediate the antifibrillatory effect of transient acidic reperfusion. PMID- 8456983 TI - Role of nitric oxide in hypoxic coronary vasodilatation in isolated perfused guinea pig heart. AB - To test the hypothesis that nitric oxide (NO) mediates hypoxic coronary dilatation in situ, isolated guinea pig hearts were perfused at constant pressure (Langendorff technique) with physiological salt solution. Switching from a control perfusate (95% O2-5% CO2) to one equilibrated with a lower O2 tension (20% O2) induced a large, but submaximal and reproducible, coronary dilatation. The NO synthase inhibitor NG-nitro-L-arginine (L-NNA) diminished baseline flow (3.67 +/- 0.24 vs. control 5.11 +/- 0.42 ml.min-1 x g-1; P < 0.05) and selectively blocked the coronary flow response to acetylcholine without reducing the response to papaverine. L-NNA reduced the absolute increase in coronary flow during hypoxia by 27 +/- 2% (delta flow = 5.83 +/- 0.49 vs. control delta flow = 8.04 +/- 0.74 ml.min-1 x g-1; P < 0.05). Hypoxic coronary dilatation was unaffected by infusion of the thromboxane mimetic U-46619, which decreased baseline coronary flow to the same extent as L-NNA. Prior addition of indomethacin did not alter the attenuating effect of L-NNA. Hypoxic coronary dilatation during constant flow perfusion at 14.7 +/- 0.28 ml/min was reduced by 65 +/- 5% after L-NNA. Therefore, the NO component of the response was not a consequence of the reduced baseline flow observed in the presence of L-NNA, did not depend on prostaglandin synthesis, and was not secondary to increased flow or intravascular shear stress. We conclude that hypoxic coronary vasodilatation in isolated guinea pig hearts is partially mediated by NO. PMID- 8456984 TI - A factor released from coronary vascular endothelium inhibits myocardial contractile performance. AB - The effect of continuous intracoronary infusion of bradykinin (BK; 10(-6) M) on the myocardial contractile performance of isolated Langendorff-perfused ferret hearts was investigated. BK produced a transient but marked inhibition of contractile performance, the changes being fully resolved by 2-3 min. This effect of BK was blocked after disruption of the coronary vascular endothelium with Triton X-100 (0.5%). Prior infusion of the endothelium-derived relaxing factor (EDRF) synthesis inhibitor N omega-nitro-L-arginine (10(-4) M) failed to alter the mechanical effects induced by BK. These changes in contractile performance were reduced, however, by the K+ channel-blocking agent glibenclamide (10(-6) M) but were unaffected by tetrapentylammonium bromide (5 x 10(-5) M) or 4 aminopyridine (10(-3) M). These findings therefore indicate that BK inhibits myocardial contractile performance by opening myocardial ATP-sensitive K+ channels, probably via the release of an endothelium-derived factor unrelated to EDRF. PMID- 8456985 TI - Effects of diabetes on myocardial glucose transport system in rats: implications for diabetic cardiomyopathy. AB - Biochemical mechanisms underlying impaired myocardial glucose utilization in diabetes mellitus have not been elucidated. We studied sarcolemmal vesicles (SL) in control, streptozotocin-induced diabetic (D), and insulin-treated diabetic (Tx) rats and found that 3-O-methylglucose transport rates were decreased 53% in D rats and were normalized by insulin therapy. Immunoblot analyses of SL revealed that GLUT4 glucose transporters were decreased 56% in D and were normal in Tx rats. Thus diminished transport rates could be fully explained by reduced numbers of SL GLUT4 with normal functional activity. To determine whether SL GLUT4 were decreased due to tissue depletion or abnormal subcellular distribution, we measured GLUT4 in total membranes (SL plus intracellular fractions). Total GLUT4 (per mg membrane protein or per DNA) was decreased 45-51% in D [half time = 3.5 days after streptozotocin], and these values were restored to normal in Tx rats. Also, diabetes decreased GLUT4 mRNA levels by 43%, and this effect was reversed by insulin therapy. We conclude that, in diabetes, 1) impaired myocardial glucose utilization is the result of a decrease in glucose transport activity, and 2) transport rates are reduced due to pretranslational suppression of GLUT4 gene expression and can be corrected by insulin therapy. GLUT4 depletion could limit glucose availability under conditions of increased workload and anoxia and could cause myocardial dysfunction. PMID- 8456986 TI - Effects of cocaine on sarcoplasmic reticulum in skinned rat heart muscle. AB - We examined the effects of cocaine on the ability of the sarcoplasmic reticulum (SR) to release and accumulate Ca2+ and on the Ca2+ sensitivity of the contractile proteins using chemically skinned rat left ventricular muscles. The preparations were treated with saponin (40 micrograms/ml for Ca2+ release and uptake studies and 200 micrograms/ml for Ca(2+)-tension experiments). The SR was loaded with 10(-6) M Ca2+ solution; SR Ca2+ release was induced by application of 5 or 25 mM caffeine. The amount of Ca2+ released from the SR was estimated by the area under the caffeine-induced transient contraction. After 1 min of SR Ca2+ loading, simultaneous application of 50 microM cocaine and 5 mM caffeine increased caffeine-induced Ca2+ release by 15.7 +/- 3.1% (P < 0.05). However, when Ca(2+)-loaded preparations were treated with cocaine for 1 min before application of 5 mM caffeine, caffeine-induced Ca2+ release was reduced by 17.1 +/- 3.0% (P < 0.05). When cocaine was applied during the Ca2+ loading periods, the amount of Ca2+ accumulated by the SR (the area under the 25 mM caffeine induced contraction) increased for both 1-min (10.9 +/- 1.7%, P < 0.05) and 3-min (15.5 +/- 4.4%, P < 0.05) Ca2+ loading periods. Cocaine (50 microM) had no effect on the Ca2+ sensitivity of the contractile system. We conclude that cocaine at a concentration of 50 microM can directly alter the ability of the SR to release and accumulate Ca2+. These effects of cocaine, especially those on SR Ca2+ release, may play a role in its potential for induction of cardiac toxicity. PMID- 8456987 TI - In vivo cerebrovascular reactivity in Wistar and Fischer 344 rat strains during aging. AB - Basal cerebral blood flow (CBF) and CBF regulation after hypercapnia and hypotensive hemorrhage were investigated using H2 clearance in the frontal cortex of awake 2-, 14-, or 23-mo-old Wistar or Fischer 344 rats. Basal CBF decreased in old Wistar but not in mature Wistar (old 64.4 +/- 2.8, mature 87.6 +/- 2.6, young 79.6 +/- 2.2 ml.min-1 x 100 g-1) or in old Fischer 344 (old 71.9 +/- 2.9, young 73.3 +/- 1.6 ml.min-1 x 100 g-1) rats. Cerebrovascular reactivity to hypercapnia decreased in mature and old Wistar (old 2.1 +/- 0.3, mature 3.1 +/- 0.7, young 7.0 +/- 2.1 ml.min-1 x 100 g-1 x mmHg-1) but not in old Fischer 344 rats (old 4.6 +/- 1.4, young 4.9 +/- 0.9 ml.min-1 x 100 g-1 x mmHg-1). The lower limit of CBF autoregulation increased by 20 mmHg during maturation and/or aging in the two strains. Because blood gases and pH evolved similarly in both strains, we postulate that differences in cerebrovascular structure and/or function explain the differences in CBF regulation in the older representatives of the two strains. PMID- 8456988 TI - Endothelium-dependent contractions to oxygen-derived free radicals in the canine basilar artery. AB - Experiments were designed to determine the effect of oxygen-derived free radicals in isolated canine basilar arteries. Rings with and without endothelium were suspended for isometric tension recording in modified Krebs-Ringer bicarbonate solution bubbled with 95% O2-5% CO2 (temperature = 37 degrees C; pH = 7.4). A radioimmunoassay technique was used to measure production of prostaglandins and thromboxane B2. Xanthine oxidase (1-9 mU/ml, in the presence of 10(-4) M xanthine) and hydrogen peroxide (10(-6) to 10(-4) M) caused concentration dependent contractions. The removal of endothelium reversed these contractions into relaxations. Contractions to xanthine oxidase and hydrogen peroxide were inhibited in the presence of superoxide dismutase (150 U/ml), catalase (1,200 U/ml), indomethacin (10(-5) M), and SQ 29548 (10(-6) M) but not in the presence of deferoxamine (10(-4) to 10(-3) M) and dimethyl sulfoxide (10(-4) M). NG monomethyl-L-arginine (3 x 10(-5) M) augmented the contractions to hydrogen peroxide. Xanthine oxidase stimulated production of 6-ketoprostaglandin F1 alpha, prostaglandin F2 alpha, prostaglandin E2, and thromboxane B2. The stimulatory effect was prevented by the removal of endothelial cells. These studies suggest that xanthine oxidase causes endothelium-dependent contractions mediated by: 1) hydrogen peroxide-induced stimulation of the endothelial metabolism of arachidonic acid via the cyclooxygenase pathway, leading to activation of prostaglandin H2-thromboxane A2 receptors, and 2) inactivation of basal production of nitric oxide by superoxide anions. PMID- 8456989 TI - Effects of oxygen and exogenous L-arginine on EDRF activity in fetal pulmonary circulation. AB - To determine whether L-arginine, the precursor of endothelium-derived relaxing factor (EDRF), increases vasodilator activity in the fetal pulmonary circulation, we studied its effects on basal pulmonary vascular tone and on pulmonary vasodilation stimulated by oxygen and acetylcholine (ACh) in chronically prepared late-gestation fetal lambs. L-Arginine infusion (30-300 mg over 10 min) into the left pulmonary artery (LPA) increased blood flow (18-57%) without changing pulmonary artery pressure. To determine whether O2-induced vasodilation involves EDRF and is augmented by L-arginine treatment, we infused L-arginine or NG-nitro L-arginine (L-NNA), an inhibitor of EDRF synthesis, while increasing fetal PO2 6 Torr by delivering 100% O2 to the ewe for 120 min. In controls, LPA blood flow progressively increased from 106 +/- 13 ml/min (baseline) to 257 +/- 34 ml/min (peak) at 40 min of increased PO2 (P < 0.05, baseline vs. peak) but steadily returned toward baseline during the next hour. Treatment with L-NNA markedly attenuated O2-induced pulmonary vasodilation (P < 0.05 vs. control). L-Arginine infusion did not augment or sustain the O2-induced vasodilator response. We also examined whether L-arginine could sustain pulmonary vasodilation to ACh, another EDRF-dependent stimulus, and found that the EDRF substrate neither potentiated nor sustained the ACh response. We conclude that: in the fetal lung 1) exogenous L-arginine is a fetal pulmonary vasodilator, 2) increased PO2 augments EDRF activity in the fetal lung, and 3) supplemental L-arginine does not sustain either O2- or ACh-induced vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8456990 TI - Contribution of wall mechanics to the dynamic properties of aortic baroreceptors. AB - To examine the contribution of wall mechanics to dynamic properties of baroreceptors, we subdivided the transfer function of baroreceptors into two subsystems [aortic pressure to diameter and diameter to aortic depressor nerve activity (ANA)]. In six alpha-chloralose-anesthetized rabbits, we measured pressure, diameter, and ANA while randomly perturbing pressure. We obtained transfer functions (pressure to ANA, diameter to ANA, and pressure to diameter) by taking the ratio of crosspower spectrum to the input power spectrum (0.005-5 Hz). Below 3 Hz, the transfer function from pressure to ANA was nearly identical to that from diameter to ANA, whereas that from pressure to diameter was flat. Using transfer functions we could reproduce adaptation and hysteresis that were quantitatively similar between pressure-ANA transduction and diameter-ANA transduction. The pressure-diameter relationship was almost instantaneous and thus showed no hysteresis. In a second group of rabbits, the ratio of the shift of the hysteresis loop was unchanged by ouabain (40 micrograms/kg iv, n = 7). We conclude that the dynamic properties of baroreceptors may not be related to the wall mechanics or the Na(+)-K(+)-adenosinetriphosphatase activity. PMID- 8456991 TI - Transvascular albumin flux in rabbit hindlimb after tourniquet ischemia. AB - Transvascular clearance of labeled rabbit albumin was measured in gastrocnemius muscle and heel skin from anesthetized rabbits after 1 or 2 h of tourniquet ischemia. Albumin clearance, calculated as a 1-h extravascular uptake, was 4.7 +/ 0.4 and 29 +/- 1 microliter.h-1 x g dry wt-1 for control gastrocnemius muscle and heel skin, respectively. During the first hour of reperfusion, the clearance was 101 +/- 23 and 56 +/- 6 microliters.h-1 x g dry wt-1 in the muscle and skin, respectively. The clearance in skin during the second and third hour of reperfusion was not different from control. The increased clearance in muscle persisted during 2 h of reperfusion but returned to control levels during the third hour of reperfusion. The solvent drag reflection coefficient was measured by increasing venous pressure during reperfusion in one leg after bilateral ischemia. In skin, the reflection coefficient, calculated as 1 minus the change in clearance divided by the change in water weight, was 0.94 +/- 0.05 and did not change with tourniquet ischemia. The reflection coefficient in muscle was 0.98 +/ 0.01 for control animals and decreased to 0.66 +/- 0.11 during the first hour of reperfusion. The reflection coefficient was not different from control during the third hour of reperfusion. The transitory increase in microvascular permeability to albumin in skeletal muscle is more indicative of an acute inflammatory response than of endothelial injury. PMID- 8456992 TI - Effects of leukocyte activation on capillary hemodynamics in skeletal muscle. AB - Leukocytes may be an important determinant of microvascular resistance, particularly during pathological states that cause cell activation and cytoplasmic stiffening. Significant mechanisms include capillary plugging and venular adhesion. Previous quantitative studies on leukocyte-capillary plugging focused solely on arteriolar-capillary branchpoints. There are no quantitative data on plugging throughout the capillary network either under normal conditions or after leukocyte activation. Plugging measurements were made throughout capillary networks at both arteriolar-capillary and capillary-capillary branchpoints in spinotrapezius muscle of anesthetized rats under normal physiological conditions and after leukocyte activation by superfusion with 1 x 10(-7) M N-formyl-methionyl-leucylphenylalanine (FMLP). These data were used to estimate the increase in microvascular flow resistance due to leukocyte plugging. The increase was 1.1% in control and 15.9% in the activated state. On an individual network basis, this represents an average 23-fold increase (P < 0.002) in network resistance, suggesting that leukocyte activation has a significant impact on microvascular blood flow. PMID- 8456993 TI - Abnormal responses to pulmonary vasodilators in conscious dogs after left lung autotransplantation. AB - We investigated the extent to which left lung autotransplantation (LLA) alters endothelium-dependent (bradykinin and acetylcholine) and endothelium-independent (sodium nitroprusside) vasodilation in the pulmonary circulation of conscious dogs. Continuous left pulmonary vascular pressure-flow (LPQ) plots were generated in conscious dogs 3-4 wk post-LLA and in sham-operated controls. LLA resulted in a marked upward shift in the baseline LPQ relationship compared with the control group (P < 0.01), i.e., LLA caused a chronic increase in pulmonary vascular resistance. The thromboxane analogue, U-46619, was used to acutely preconstrict the pulmonary circulation in control dogs, which shifted the control LPQ relationship to the same position measured post-LLA. Under these circumstances, bradykinin, acetylcholine, and nitroprusside caused pulmonary vasodilation in the control group, whereas these responses were either attenuated or reversed to vasoconstriction post-LLA. After acute preconstriction with U-46619 post-LLA, the pulmonary vasodilator responses to bradykinin and acetylcholine were again attenuated, but the response to nitroprusside was unaltered compared with control. These results indicate that a significant component of the chronic increase in pulmonary vascular resistance post-LLA is passively mediated and does not reflect an active increase in baseline vasomotor tone. Moreover, LLA results in an impairment in endothelium-dependent, but not endothelium-independent, pulmonary vasodilation in conscious dogs. PMID- 8456994 TI - Myocardial blood flow and VO2 in lambs with an aortopulmonary shunt during strenuous exercise. AB - To determine how much myocardial O2 consumption (VO2) would increase during an additional load on the heart in shunt as compared with control lambs, we studied 12 7-wk-old lambs with an aortopulmonary left-to-right shunt (59 +/- 3% of left ventricular output, mean +/- SE) and 11 control lambs during exercise at 80% of their predetermined peak VO2 (VO2peak), at 12 +/- 1 days after surgery. During exercise, systolic aortic pressure increased by 25% in the two groups. Left atrial pressure and left ventricular stroke volume did not change significantly and remained considerably higher in shunt than in control lambs. Heart rate, however, increased less in shunt than in control lambs (163 +/- 8 to 235 +/- 8 vs. 107 +/- 7 to 230 +/- 8 beats/min). The same was true for left ventricular myocardial blood flow (245 +/- 19 to 391 +/- 27 vs. 128 +/- 10 to 320 +/- 45 ml.min-1 x 100 g-1) and myocardial VO2 (847 +/- 101 to 1,692 +/- 136 vs. 528 +/- 58 to 1,579 +/- 178 mumol O2 x min-1 x 100 g-1). We conclude that, despite the volume load, myocardial VO2 of shunt lambs does not increase to a greater extent than in control lambs during a considerable additional load on the heart. PMID- 8456995 TI - Short time-scale LV systolic dynamics: pressure vs. volume clamps and effect of activation. AB - We recently proposed a new model-based approach to quantifying short time-scale left ventricular (LV) systolic dynamics. In this study we examine the hypothesis that the quantitation of LV dynamics using the proposed approach is independent of external mechanical perturbations and the level of activation. Mechanical perturbation independence was assessed in seven isolated ferret hearts in which controlled changes in pressure (pressure clamp) or volume (volume clamp) were introduced at the time of peak isovolumetric pressure (protocol 1), and responses to these clamps were analyzed over the first 16 ms. The model described both pressure- and volume-clamps responses equally well. Model parameters were not different among various pressure clamps, and parameters estimated from volume clamps could accurately predict responses to pressure clamps [r2 range: 0.993 0.999; normalized root-mean-square error (NRMSE) range: 2.35-5.86%]. To examine activation independence, volume- (4 hearts) and pressure-clamp (4 hearts) responses were obtained and analyzed for baseline and postextrasystolic potentiated beats in a manner similar to protocol 1. The model parameter values estimated from the baseline state accurately predicted responses for the postextrasystolic potentiated state (r2 and NRMSE range for volume-clamp data: 0.989-0.998 and 3.35-6.88%, respectively; r2 and NRMSE range for pressure-clamp data: 0.992-0.996 and 4.26-5.23%, respectively). Thus the proposed approach can dissect the contributions of changes in activation from those due to changes in contractile unit properties on the function of the intact LV. PMID- 8456996 TI - Production of arachidonic acid metabolites in adult rat cardiac myocytes, endothelial cells, and fibroblast-like cells. AB - Cells were incubated in the presence of the Ca2+ ionophore A23187 (10 microM) and arachidonic acid (AA, 80 microM). The release of eicosanoids from subcultivated cardiac endothelial and fibroblast-like cells amounted to 23.3 +/- 4.5 and 2.0 +/ 0.4 nmol/mg cellular protein per 30 min, respectively. The release from isolated cardiomyocytes remained below the detection limit of the high-performance liquid chromatography assay (< 0.00015 nmol/assay). When a very sensitive radioimmunoassay was applied, cardiomyocytes released 0.002 +/- 0.0001 nmol prostacyclin per milligram cellular protein per 30 min. Prostaglandin (PG) E2 and PGF2 alpha, 12-hydroxyheptadecatrienoic acid, 11- and 15-hydroxyeicosatetraenoic acid, and thromboxane B2 were the main eicosanoids released by endothelial cells. The stable product of prostacyclin, 6-keto-PGF1 alpha, contributed relatively little to the total amount of eicosanoids formed by endothelial cells. Fibroblast like cells released predominantly PGE2 and 6-keto-PGF1 alpha and, to a lesser extent, 12-hydroxyheptadecatrienoic and 15-hydroxyeicosatetraenoic acids. Neither endothelial cells nor fibroblast-like cells released leukotrienes. A23187 stimulated eicosanoid release from endothelial cells when exogenous AA was below 40 microM. Addition of albumin reduced the amount of eicosanoids produced. Histamine and bradykinin did not influence 6-keto-PGF1 alpha and PGE2 production in cardiomyocytes. Histamine only gave rise to a slight but significantly higher release of 6-keto-PGF1 alpha in endothelial cells. PMID- 8456998 TI - Variable cross-bridge cycling-ATP coupling accounts for cardiac mechanoenergetics. AB - Cardiac twitch contractions were simulated by Huxley's sliding filament cross bridge muscle model coupled with parallel and series elastic components. The energetics of the contraction were based on the ATP hydrolysis for the cross bridge cycling. Force-length area (FLA), as a measure of the total mechanical energy, was computed for both isometric and isotonic contractions in a manner similar to the pressure-volume area (PVA) (Suga, H. Physiol. Rev. 70: 247-277, 1990). PVA correlates linearly with cardiac oxygen consumption, and since FLA is analogous to PVA, FLA should correlate with the ATP expended. Simulations comparing FLA with the cross-bridge cycling ATP usage showed that at lower muscle fiber activation levels (shorter initial fiber lengths and lower preload levels) FLA decreased more rapidly than the number of muscle fiber cross-bridge cycles in both isometric and isotonic contraction cases. This suggests that one ATP can cause more than one cross-bridge cycle at lower activation levels as was proposed by Yanagida, Arata, and Oosawa (Nature 316: 366-369, 1985). If the number of cross-bridge cycles to ATP ratio is allowed to increase at lower activation levels as suggested by Yanagida et al., Huxley's model is compatible with the experimental findings on FLA and PVA. PMID- 8456997 TI - Response of the hypertrophied left ventricle to tachycardia: importance of maturation. AB - Pressure overload left ventricular (LV) hypertrophy (LVH) induces ventricular dysfunction during stress, which is commonly attributed to diminished myocardial capillary density and ischemia. Immature hearts with LVH have a normal coronary flow reserve and capillary density. The purpose of this study was to determine 1) whether young lambs with LVH had an abnormal response to chronotropic stress, 2) whether nonischemic mechanisms contributed to the abnormal response, and 3) whether the age at which LVH was induced affected the response. We assessed LV endomyocardial function, perfusion, and Ca(2+)-adenosinetriphosphatase (ATPase) mRNA levels in chronically instrumented lambs with and without LVH and adult sheep with and without LVH. Rapid pacing induced diastolic dysfunction, increased time constant of isovolumic relaxation using an iterative fit (tM), and elevated LV diastolic pressures in young lambs and adult sheep with LVH. During pacing, tM was greater in the adult sheep with LVH than in the young lambs with LVH. Ca(2+) ATPase mRNA levels were 79% less in adult sheep with LVH than in those without. Ca(2+)-ATPase mRNA levels in lambs with and without LVH and adult sheep without LVH were similar. Diastolic dysfunction occurred in the absence of subendomyocardial hypoperfusion, suggesting a nonischemic mechanism. In adult sheep with LVH diastolic dysfunction was associated with a marked reduction in Ca(2+)-ATPase mRNA levels. PMID- 8456999 TI - Limitations of methods of osmometry: measuring the osmolality of biological fluids. AB - Osmometry is an important tool in the investigation of biological phenomena, and commercially available instruments for freezing point and vapor pressure osmometry can determine the osmolality of solutions quickly and inexpensively. However, accurate measurements of osmolality using these techniques require that the solutions have specific characteristics, and that measurements do not exceed the limitations inherent to each method or instrument. The thermodynamic principles underlying osmometry constrain the range and accuracy of each measurement method, and these must be considered in establishing the usefulness of each technique. This paper addresses the principles and limitations of routine osmometry techniques. We begin by discussing definitions of osmolality and the thermodynamic concepts of solute-solvent systems that are central to understanding osmometry of biological (i.e., aqueous) solutions. We then explore the application of various methods of measuring osmolality, the nature of errors introduced by overextension or misapplication of osmometry techniques, and the interpretation of data in the literature acquired by various methods and protocols. PMID- 8457000 TI - Biochemical bases for difference in oxygen affinity of maternal and fetal red blood cells of rattlesnakes. AB - Pregnancy in Crotalus viridis oreganus is associated with an increase in the nucleoside triphosphate (NTP) concentration and a concomitant decrease in the oxygen affinity of the adult red blood cell. However, although the red blood cells of non-pregnant adults and fetuses have indistinguishable NTP concentrations, they have different oxygen affinities. Therefore, red blood cell NTP concentrations alone cannot account for the oxygen-affinity difference between fetal and maternal red blood cells. Hemoglobins from adult and fetal snakes had similar intrinsic oxygen affinities; however, adult hemoglobin was more responsive to organic phosphate modulation compared with fetal hemoglobin. Structural differences, indicated by native gel electrophoresis and electrophoresis of the globins under denaturing conditions at high pH, corroborated functional differences of hemoglobins from fetus and adult. Therefore, the biochemical basis for the oxygen-affinity difference between maternal and fetal red blood cells in this rattlesnake appears to be unique. It appears to be caused by a functionally distinct fetal hemoglobin and the pregnancy-associated rise in red blood cell NTP levels in the mother. PMID- 8457001 TI - Lactate and glucose metabolism in mouse (Mus musculus) and reptile (Anolis carolinensis) skeletal muscle. AB - The reliance on anaerobic metabolism during exercise in lizards has been the subject of a growing body of literature in activity metabolism. Prior studies have demonstrated that lizards rely more on postexercise lactate to regenerate depleted glycogen stores than do many mammals. These studies prompted an in vitro comparison between the metabolic mechanisms for the handling of lactate and glucose in the muscles of a small mammal and lizard. Hindlimb muscles of Mus and Anolis were stimulated to fatigue and then incubated in the presence of 15 mM lactate and either 5.5 (mice) or 8.5 (anoles) mM glucose. Oxidation rates of lactate and glucose were seven to eight times higher in mice. Both species oxidized more lactate than glucose (8 to 9 times). However, anole muscle showed a preference for lactate as a substrate for glycogenesis, incorporating 1.5 times as much lactate (expressed in glucose equivalents) as glucose. In contradistinction, mice incorporated 2.8 times as much glucose into glycogen as lactate. The quantitative differences in metabolic scope of mammals and reptiles are accompanied by fundamental differences in the capacity and patterns of skeletal muscle metabolism of lactate and glucose. PMID- 8457002 TI - Independence of salt intake induced by calcium deprivation from the renin angiotensin-aldosterone system. AB - We investigated whether the elevated NaCl intake shown by calcium-deprived rats is mediated by the renin-angiotensin-aldosterone system. First, we looked for manifestations of altered renin-angiotensin-aldosterone system activity during the progression of calcium deficiency. There were no differences between control and calcium-deprived rats in plasma aldosterone concentrations, plasma renin activity, plasma sodium concentrations, sodium balance, or blood pressure. Second, we used selective pharmacological antagonists to examine whether disruption of the renin-aldosterone-angiotensin system influenced salt intake. Blockade of aldosterone receptors with spironolactone (25 mg.kg-1 x day-1 sc for 7 days) had no effect on NaCl intake of control or calcium-deprived rats. Angiotensin AT1 receptor blockade with losartan potassium (0.5-10 mg/kg orally) had no effect on NaCl intake of control or calcium-deprived rats but doses > 0.5 mg/kg decreased NaCl intake of adrenalectomized rats. Taken together, these findings indicate that the renin-angiotensin-aldosterone system does not mediate the increased NaCl intake produced by calcium deficiency. The appetite for salt produced by calcium deficiency involves a different physiological substrate from most other models of NaCl intake. PMID- 8457003 TI - Independence of salt intake from the hormones regulating calcium homeostasis. AB - Rats deprived of dietary calcium increase voluntary intake of NaCl solutions. We investigated whether the major hormones controlling calcium homeostasis are responsible for this increase in salt intake. Removing endogenous sources of calcitonin and parathyroid hormone by thyroidectomy and/or parathyroidectomy had no effect on NaCl intake. The surgically compromised rats and their intact controls drank similar amounts of NaCl in response to manipulations of diet calcium content. Despite normal NaCl intakes, rats with parathyroidectomy had low plasma calcium concentrations and a strong appetite for 50 mM CaCl2 solution. Chronic infusion of parathyroid hormone into rats with thyroparathyroidectomy decreased NaCl intake. Intact rats fed an American Institute of Nutrition (AIN) 76A-based vitamin D-deficient diet increased NaCl intake slightly and showed a strong appetite for CaCl2, but other rats maintained normocalcemic by the addition of calcium, phosphorus, and lactose to the vitamin D-deficient diet had normal NaCl and CaCl2 intakes. Chronic infusions of 1,25-dihydroxyvitamin D3 into intact rats had no effect on NaCl intake. Taken together, these results indicate that the increase in NaCl intake produced by calcium deprivation is not mediated by changes in circulating levels of calcium, calcitonin, parathyroid hormone, or 1,25-dihydroxyvitamin D3. Furthermore, the major calcium-regulating hormones are not involved in the control of "spontaneous" NaCl intake in the rat. PMID- 8457004 TI - Mechanisms for the diuresis of acute cold exposure: role for vasopressin? AB - The hypothesis that inhibition of vasopressin (VP) secretion initiates cold induced diuresis was tested in six Brattleboro homozygous (diabetes insipidus, DI) rats exposed to 60 min at 5 degrees C. For 9-14 days before cold exposure (CE) the rats were treated with VP (750 pg.kg-1.min-1) subcutaneously via osmotic minipumps. Eight vehicle-treated Long-Evans (LE) rats characterized the response to acute exposure at 5 degrees C. Additional groups of six to eight LE and six DI rats were infused with VP (30-90 pg.kg-1.min-1 iv) on the day of CE. The DI rats receiving chronic VP replacement and untreated LE rats exhibited cold-induced diuresis, with peak increases in urine flow (V) of 63 +/- 12 (DIs) and 29 +/- 4 (LEs) microliters.min-1 x 100 g body wt-1. LE rats acutely infused with VP exhibited a diuresis at the two lower doses (peak V was 18 +/- 3 at the 30 and 18 +/- 4 microliters.min-1 x 100 g body wt-1 at the 60 pg.kg-1.min-1 dose), but the diuretic response was completely blunted at the uppermost dose of VP. Cold induced diuresis was absent at the lowest VP dose in the acutely infused DI rats. A pressor response (30-36 mmHg) to CE was noted with all treatment groups, including those that did not exhibit a diuresis. No changes in glomerular filtration rate (GFR) with CE were observed. These data suggest that when plasma VP levels are controlled by prolonged infusion of VP in the DI rats, other mechanisms can operate to initiate cold-induced diuresis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457005 TI - Sodium appetite in response to sodium deficiency in baboons. AB - Naive male baboons exhibit little hedonic intake of 300 mM NaCl but develop a robust Na appetite with Na deficiency. With the first episode of Na deficiency, increased drinking of saline solution occurs in the first 1-3 days, but correction of deficit is slow over 5-6 days. Na intake and repair of deficit become more rapid with experience. After three episodes of Na deficiency, the baboons immediately drink Na solution when given access and repair the deficit over 1-2 days. These experimental data showing an innate Na appetite in primates are important in relation to behavior of gorillas and chimpanzees in the wild and anthropological records of behavior toward salt sources. They open an avenue for physiological analysis of cerebral mechanisms subserving Na appetite in primates and humans. PMID- 8457006 TI - Pedunculopontine stimulation alters respiration and increases ACh release in the pontine reticular formation. AB - The present study examined the hypothesis that cholinergic neurons in the pedunculopontine tegmental nucleus (PPT) can cause the release of acetylcholine (ACh) in the pontine reticular formation and contribute to respiratory depression. In vivo microdialysis of the gigantocellular tegmental field (FTG) was performed in 10 adult male cats while respiration was being measured. In four intact, unanesthetized cats these measurements were obtained during states of quiet wakefulness and during the rapid eye movement (REM) sleeplike state caused by FTG microinjections of carbachol. The results demonstrate a simultaneous time course of enhanced ACh release in the FTG and respiratory rate depression. In six barbiturate-anesthetized cats similar measurements were obtained while PPT regions containing NADPH-positive neurons were electrically stimulated. PPT stimulation caused increased ACh release in the FTG and caused respiratory rate depression. Together, these findings are consistent with the hypothesis of a causal relationship between ACh release in the FTG and respiratory depression. PMID- 8457007 TI - Osmoregulation of the magnocellular system during pregnancy and lactation. AB - We compared the responsiveness of both the vasopressin (VP) and oxytocin (OT) magnocellular systems to osmotic stimulation during pregnancy and lactation to determine if changes in thresholds and sensitivities were similar for both neuropeptides. Virgin, pregnant (day 20), and lactating (day 6) Sprague-Dawley rats were injected with a hypertonic NaCl solution (0.25 M-8.0 M NaCl; 15 ml/kg sc) and decapitated 2 h later. Late in gestation, the apparent osmotic threshold for both VP and OT release was lower by approximately 10 mosmol/kgH2O than that of virgin and lactating animals. The sensitivity (i.e., slope of the linear regression relating plasma osmolality and VP or OT levels) of the magnocellular system to osmoregulation, however, was unchanged in pregnant animals but was significantly attenuated (P < 0.01) for both peptides during lactation (slopes of lactating vs. virgin rats: OT, 1.7 vs. 3.4; VP, 1.1 vs. 1.9). The neural lobe content of VP decreased (P < 0.05) in pregnant rats, whereas OT stores were reduced (P < 0.05) in lactating animals. Thus, during pregnancy, the lower tonicity of plasma is perceived as normal by both VP and OT neuroendocrine systems enabling excretion of an acute sodium or water load. PMID- 8457008 TI - The doubly labeled water method: errors due to deuterium exchange and sequestration in ruminants. AB - The doubly labeled water (DLW) technique allows the CO2 production (rCO2) of free living animals to be estimated from the difference between the turnover of 2H2O and H218O in the body water. A fundamental assumption of this technique is that neither of the isotopes used are lost in products other than CO2 and H2O. We found, however, that 2H was lost in both exchangeable and nonexchangeable positions in the feces of sheep. Negligible amounts of 18O were lost in exchangeable positions. 2H losses led to a 0.75% (SE 0.06, n = 4) overestimation of the measured 2H2O flux, leading to an average error in rCO2 estimates of 20.3 l/day. For a typical rCO2 rate of 370 l/day, this would amount to an error of approximately 5% (range -7.0 to -4.3%, n = 4). Correction factors to account for this loss were presented. The error in rCO2 due to 2H sequestration into fat was calculated to be at most 2.1 l/day or about -0.66% in lambs with a rCO2 of 320 l/day. In a triply labeled water (TLW) study the maximum error in the estimation of fractionated evaporative water loss (X) would lead to a 0.81% underestimation of rCO2. We recommend that during a DLW study involving ruminant animals the correction factors presented here be used to compensate for 2H loss in feces. This may be particularly important where the diet has a high roughage content leading to a significant fecal dry matter production. PMID- 8457009 TI - Decreased availability of metabolic fuels suppresses estrous behavior in Syrian hamsters. AB - The availability of oxidizable metabolic fuels affects reproductive physiology and behaviors in female mammals. In Syrian hamsters, 48 h of food deprivation is sufficient to suppress secretion of gonadotropins and ovarian steroids and to prevent the occurrence of ovulation and estrous behavior. These experiments attempted to determine whether the deprivation-induced suppression of lordosis is entirely due to the disruption of ovarian steroid secretion or whether there are also changes in behavioral responsiveness to estradiol and/or progesterone (P). Estrous behavior was induced in ovariectomized hamsters with sequential injections of 5 micrograms of estradiol benzoate (EB) and 200 micrograms P. Food deprivation for 48 h, either before or just after EB treatment, significantly suppressed the amount of time females spent in lordosis during a 5-min test with a sexually experienced male. Treatment with an inhibitor of glycolysis (2-deoxy-D glucose) in combination with an inhibitor of fatty acid oxidation (methyl palmoxirate) for 48 h mimicked the effects of food deprivation and suppressed the amount of time spent in lordosis after treatment with EB+P. Given alone, neither metabolic inhibitor had an effect on lordosis. These findings indicate that suppression of hamster estrous behavior by metabolic fuel deprivation is at least in part due to a reduced responsiveness to estradiol and/or progesterone. Furthermore, estrous behavior is responsive to metabolic fuels in general. This is unlike hamster ovulatory cycles, which are primarily responsive to glucose availability. PMID- 8457010 TI - Glucoprivation induces anestrus and lipoprivation may induce hibernation in Syrian hamsters. AB - Previous results supported the notion that estrous cycles in Syrian hamsters are responsive to the general availability of metabolic fuels, rather than to either fatty acid or glucose availability per se. To test this idea, we monitored estrous cycles in hamsters that were fed ad libitum and treated with a range of doses of 2-deoxy-D-glucose (2-DG), an inhibitor of glucose utilization. Hamsters treated with 2-DG at doses ranging from 750-1,250 mg/kg showed normal estrous cycles, but higher doses (1,750 or 2,000 mg/kg) induced anestrus. While it is clear from these data that estrous cycles are affected by glucoprivation, it is not clear whether they are responsive to decreased fatty acid availability. Groups of hamsters were fed ad libitum and treated with a range of doses of methyl palmoxirate (MP), an inhibitor of fatty acid utilization. Some of the hamsters that received the highest doses became torpid and thus were not tested for lordosis. None of the euthermic, MP-treated hamsters became anestrous. Other experiments examined the role of glucose availability in fasted hamsters. Hamsters with a high body fat content were protected from fasting-induced anestrus. In contrast, fat food-deprived hamsters treated with low doses of 2-DG (750 mg/kg) became anestrous. Thus fatty acids mobilized from adipose tissue did not prevent fasting-induced anestrus when glucose utilization was blocked. One interpretation is that during fasting fatty acid utilization spares glucose for other tissues involved in the control of estrous cycles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457011 TI - Relationship between renal perfusion pressure and blood flow in different regions of the kidney. AB - The present study examined the autoregulation of blood flow in different regions of the renal cortex and medulla in volume-expanded or hydropenic anesthetized rats. Blood flow was measured in the whole kidney by electromagnetic flowmetry, in the superficial cortex with implanted fibers and external probes for laser Doppler flowmetry, and in the deep cortex and inner and outer medulla with implanted fibers for laser-Doppler flowmetry. At renal perfusion pressure > 100 mmHg, renal blood flow, superficial cortical blood flow, and deep cortical blood flow were all very well autoregulated in both volume-expanded and hydropenic rats. Inner and outer medullary blood flow were also well autoregulated in hydropenia, but blood flow in these regions was very poorly autoregulated in volume-expanded animals. As renal perfusion pressure was decreased below 100 mmHg in volume-expanded and hydropenic animals, renal blood flow, superficial and deep cortical blood flow, and inner and outer medullary blood flow all decreased. The results of these experiments demonstrate that blood flow in both the inner and outer portions of the renal medulla of the kidney is poorly autoregulated in volume-expanded rats but well autoregulated in hydropenic animals. In contrast, blood flow in all regions of the renal cortex is well autoregulated in both volume-expanded and hydropenic animals. These results suggest that changes in resistance in the postglomerular circulation of deep nephrons are responsible for the poor autoregulation of medullary blood flow in volume expansion despite well autoregulated cortical blood flow. PMID- 8457012 TI - Role of angiotensin II and prostaglandins in the regulation of uteroplacental blood flow. AB - This study was designed to determine the importance of the renin-angiotensin (RAS) and prostaglandin (PG) systems in regulating uteroplacental blood flow (UBF). Our objectives were to determine: 1) whether angiotensin II (ANG II) acts as a vasodilator or purely as a vasoconstrictor in the uteroplacental circulation, and 2) whether this circulation is capable of autoregulation. In chronically instrumented pregnant dogs (41-54 days gestation), ANG II was infused intravenously at increasing doses (8, 16, and 24 ng.kg-1 x min-1). Arterial pressure rose from 108 +/- 6 to 146 +/- 4 mmHg and UBF did not change but uterine vascular resistance (UVR) progressively increased. When the experiment was repeated while servo-controlling uterine arterial pressure, UBF fell at all doses, reaching 62 +/- 7% of control at the highest dose, and UVR increased as before. Meclofenamate (6 mg/kg i.v.) did not alter the dose-response curves. In separate experiments, uterine perfusion pressure was reduced in steps to 55 mmHg. UBF was well autoregulated down to approximately 85 mmHg, and neither captopril (14 micrograms.kg-1 x min-1) nor meclofenamate altered UBF autoregulation. Thus ANG II appears to act as a vasoconstrictor in the uteroplacental circulation and any preservation of UBF during ANG II appears to be due to the increased arterial pressure. Also, in the dog the uteroplacental circulation possesses a mild to moderate degree of autoregulatory capability, which does not appear to be dependent on the RAS or PGs. PMID- 8457013 TI - Developmental changes in renin gene expression in ovine kidney cortex. AB - The ontogeny of renin mRNA and renin content from renal cortical slices was studied in two groups of ovine fetuses at 92-94 days (0.64 gestation) and at 138 142 days (0.96 gestation), newborn lambs (0.4-2 days old), and adult sheep. Renal renin mRNA was identified by hybridization with a 32P-labeled full length rat renin cDNA. Renal renin content was measured as nanograms of angiotensin I generated per hour (active renin). There was a significant age effect on renin mRNA levels (F = 10.0, P < 0.001); values increase significantly between 0.64 and 0.95 g (P < 0.005), remain elevated in the newborns (P < 0.05), and subsequently decline in adulthood (P < 0.005). Likewise, renal renin content was significantly higher in late gestation fetuses and newborn lambs than in early gestation and adults (F = 8.3, P < 0.003). The renal renin content was strongly correlated with renin mRNA levels (R = 0.88, P < 0.0001). These results suggest that 1) the renin gene is developmentally regulated in the ovine kidney and 2) the renal content of active renin in basal conditions is regulated, at least in part, by events at the transcriptional level. PMID- 8457014 TI - Intrauterine growth retardation and fetal losses are caused by epidermal growth factor deficiency in mice. AB - The plasma concentration of epidermal growth factor (EGF) in female mice increases during pregnancy. Sialoadenectomy (surgical removal of the submandibular glands) on day 13 of gestation attenuates the rise in plasma EGF and significantly reduces the percent of live pups on day 19 of pregnancy to 80% compared with 95% for the control animals. EGF replacement therapy given to the sialoadenectomized mice successfully prevented this reduction in the percent of live pups on day 19. The average weight of the live fetuses from sialoadenectomized mothers was significantly lower than those from the control mothers, i.e., 1.00 +/- 0.14 (SD) g vs. 1.13 +/- 0.07 g. The administration of anti-EGF antiserum to the sialoadenectomized mice further affected fetal viability; only 70% of the pups were alive on day 19, with a mean weight of 0.93 +/- 0.15 g. The mean weight of the fetal body and that of the liver caused by sialoadenectomy were similarly reduced, but the brain was not affected, which shows that the growth retardation was asymmetrical. These findings suggest that EGF plays a physiological role in fetal growth and that EGF deficiency may be a cause of asymmetrical intrauterine growth retardation, which might be due to uteroplacental dysfunction. PMID- 8457015 TI - Mechanisms of renal vasodilation after protein feeding: role of the renin angiotensin system. AB - These studies were designed to determine the importance of the renin-angiotensin system (RAS) in the renal hemodynamic response to acute protein feeding. In chronically instrumented conscious dogs on a normal (80 meq/day) sodium intake, a 10 g/kg meal of raw beef caused glomerular filtration rate (GFR) to increase from 68 +/- 6 to 86 +/- 6 ml/min and effective renal plasma flow (ERPF) to increase from 211 +/- 14 to 263 +/- 15 ml/min. Plasma renin activity (PRA) was 0.44 +/- 0.14 ng ANG I.ml-1 x h-1 and did not change significantly. When the protocol was repeated during infusion of captopril, GFR increased from 67 +/- 11 to 97 +/- 10 ml/min, and ERPF rose from 264 +/- 74 to 392 +/- 82 ml/min after the meat meal. The dogs were then placed on a low-salt diet (approximately 7 meq/day) to physiologically activate the RAS. In sodium-restricted dogs, GFR increased from 71 +/- 7 to 104 +/- 10 ml/min and ERPF increased from 226 +/- 15 to 299 +/- 21 ml/min after the meat meal. PRA was 3.1 +/- 1.0 ng ANG I.ml-1 x h-1 and did not change. Thus neither blockade of the RAS with captopril nor activation of the RAS by salt restriction reduced the renal hemodynamic response to a meat meal. These data indicate that the RAS is relatively unimportant in the renal hemodynamic response to acute protein feeding. PMID- 8457016 TI - A model of pulmonary atelectasis in rats: activation of alveolar macrophage and cytokine release. AB - Although atelectasis frequently occurs after surgery and trauma, and such patients have elevated body temperatures, the mechanism of temperature elevation secondary to atelectasis is unknown. Moreover, a small animal model has not been available to study the pathophysiology of pulmonary atelectasis. The purpose of this study, therefore, was to develop a model of pulmonary atelectasis in rats. Because interleukin-1 (IL-1) and tumor necrosis factor (TNF), both potent pyrogens, are produced by macrophages during infection and inflammation, our aim was also to determine whether alveolar macrophages produce IL-1 or TNF in response to atelectasis. Whole-lung atelectasis was produced in rats by ligating the left main stem bronchus while maintaining ventilation of the right lung. After a 1-h period of atelectasis, alveolar macrophages were harvested from the right and left lungs and incubated for 24 h, and the supernatants were assayed for IL-1 and TNF. Both IL-1 and TNF levels of macrophage cultures from the atelectatic lung were significantly increased compared with the control lung. These results suggest that increased IL-1 or TNF production by alveolar macrophages may be responsible for fever caused by atelectasis. PMID- 8457017 TI - Melatonin injections affect circadian behavior and SCN neurophysiology in Djungarian hamsters. AB - We investigated the effects of daily melatonin (MEL) injection on phase angle of entrainment, duration of wheel-running activity (alpha), and frequency of suprachiasmatic nuclei (SCN) neuronal discharge in the photo-nonresponsive phenotype of the Djungarian hamster, Phodopus sungorus. Photo-nonresponsiveness is characterized by an absence of physiological adjustments to short days (SD). With respect to wheel-running activity, photo-nonresponsive hamsters have a large negative phase angle of entrainment and a compressed alpha under SD. These hamsters also have a delayed nocturnal MEL pulse. These circadian differences are correlated with the daily profile of SCN neuronal activity. In the present experiments, daily MEL injections to photo-nonresponsive hamsters resulted in molt, gonadal regression, and expansion in alpha until entrainment to lights off. Vehicle-injected controls did not exhibit any of these responses. SCN neuronal activity patterns recorded from MEL-injected photo-nonresponders, but not vehicle injected controls, resembled electrical activity profiles of photoresponsive hamsters. These results demonstrate that MEL induces "photoresponsiveness" in previously photo-nonresponsive hamsters, that MEL modifies circadian behavior to resemble that of photoresponders, and that MEL injections affect the circadian rhythm of SCN neuronal firing. PMID- 8457018 TI - Prevention of secondary cardiovascular instability after intestinal ischemia and reperfusion improves survival. AB - Previous studies of small intestinal ischemia and reperfusion (I/R) in immature rats report secondary systemic organ injury and low survival rates; however, in these studies the cardiovascular stability of the rat was not established. To prevent the secondary hemodynamic deterioration accompanying intestinal I/R, we have developed a model that utilizes aggressive fluid resuscitation. Under anesthesia, 4-wk-old male Sprague-Dawley rats (n = 189) underwent 90 min of I/R (superior mesenteric artery occlusion) or sham (SH) operation while receiving lactated Ringer with 5% dextrose at 15 (IR15, SH15) or 65 (IR65, SH65) ml.kg-1 x h-1 i.v. The results indicate that aggressive fluid resuscitation in the IR65 group significantly attenuated the hypotension, hemoconcentration, metabolic acidosis, and amount of gross bowel injury observed in the IR15 group, while increasing postreperfusion renal and intestinal blood flow, prolonging survival time of nonsurvivors, and improving overall group survival. These findings suggest that maintenance of hemodynamic stability is necessary in models of bowel I/R. Furthermore, this model allows for selective study of the isolated effects of intestinal I/R without the additional complications resulting from secondary cardiovascular instability. PMID- 8457019 TI - Gastric branch vagotomy blocks nutrient and cholecystokinin-induced suppression of gastric emptying. AB - A role for the vagus nerve in the emptying of intragastric nutrients and the gastric inhibitory actions of the brain-gut peptide cholecystokinin (CCK) has been proposed. To directly assess the role of the gastric vagal branches in these actions, we compared the emptying of 5-ml nutrient and nonnutrient gastric loads in male rats in which both branches of the gastric vagus nerves were cut (GVX, n = 7) with emptying in surgical control (n = 8) rats. Gastric emptying of saline was also examined in both groups after intraperitoneal administration of 8 micrograms/kg CCK. In control rats, high osmolarity, low pH, and caloric density all significantly decreased gastric emptying compared with the emptying of physiological saline. In addition, fat (oleic acid) and protein (peptone) loads emptied significantly more slowly than isocaloric carbohydrate (glucose) loads. Gastric branch vagotomy completely blocked the suppression of emptying produced by fat, protein, carbohydrate, and acid loads. In addition, GVX attenuated the ability of hyperosmotic nutrient and nonnutrient loads to inhibit emptying to the same degree, irrespective of their caloric content. Finally, in intact rats, CCK significantly inhibited the emptying of physiological saline, and gastric vagotomy abolished this suppression. Taken together, these results are consistent with the proposals that 1) the controlled emptying of caloric, hyperosmotic, and acidic solutions is dependent on gastric vagal branches, and 2) exogenous CCK relies on an intact vagal pathway in the control of gastric emptying. PMID- 8457020 TI - Heart rate control in normal and aborted-SIDS infants. AB - Approximate entropy (ApEn), a mathematical formula quantifying regularity in data, was applied to heart rate data from normal and aborted-sudden infant death syndrome (SIDS) infants. We distinguished quiet from rapid-eye-movement (REM) sleep via the following three criteria, refining the notion of REM as more "variable": 1) REM sleep has greater overall variability (0.0374 +/- 0.0138 vs. 0.0205 +/- 0.0090 s, P < 0.005); 2) REM sleep is less stationary (StatAv = 0.742 +/- 0.110) than quiet sleep (StatAv = 0.599 +/- 0.159, P < 0.03); 3) after normalization to overall variability, REM sleep is more regular (ApEnsub = 1.224 +/- 0.092) than quiet sleep (ApEnsub = 1.448 +/- 0.071, P < 0.0001). Fifty percent of aborted-SIDS infants showed greater ApEn instability across quiet sleep than any normal infant exhibited, suggesting that autonomic regulation of heart rate occasionally becomes abnormal in a high-risk subject. There was an association between low ApEn values and aborted-SIDS events; 5 of 14 aborted-SIDS infants had at least one quiet sleep epoch with an ApEn value below the minimum of 45 normal-infant ApEn values. PMID- 8457021 TI - The role of eosinophils in the pathogenesis of atopic dermatitis--eosinophil granule proteins as markers of disease activity. AB - Currently, there is a large body of evidence that atopic dermatitis (AD) has an immunologic basis. Atopy-specific helper T cells (Th2-like T cells) may play a pathogenetic role by producing and releasing cytokines relevant for the allergic inflammation, such as IL-4, IL-5, and other growth factors. Eosinophils are believed to be of major importance as effector cells mediating the pathogenetically relevant late-phase reaction which is associated with a significant destruction of the surrounding tissue. Accordingly, a significant preactivation of peripheral blood eosinophils was detected in AD patients, leading to an enhanced susceptibility of these cells to distinct stimuli such as IL-5. Toxic proteins, such as eosinophil cationic protein (ECP), contained in the matrix and the core of secondary granules of eosinophils, may play an important role by propagating the allergic inflammatory process and by modulating the immune response. The pathogenetic role of eosinophils in AD is further supported by the detection of these proteins in the eczematous skin of patients. Furthermore, recent data point to a significant correlation between disease activity and deposition of eosinophil granule content: ECP serum levels were significantly increased in AD patients. In addition, ECP levels correlated with the disease activity. Moreover, clinical improvement was associated with a decrease of both the clinical score and serum ECP levels. These data clearly indicate that activated eosinophils may play a major role in the allergic inflammatory process of AD. Therefore, modulation of eosinophil activation could prove to be an important pharmacologic modality for the treatment of AD. PMID- 8457022 TI - Bronchial mucosal structure after histamine inhalation. AB - Previous studies have shown an increased number of inflammatory cells and an increased level of hyaluronan in the bronchoalveolar lavage (BAL) fluid, 24 h after the inhalation of histamine. In the present report, the influence of histamine inhalation on the bronchial mucosa was, therefore, investigated in 20 subjects. Scanning electron microscopy (SEM) revealed that small areas of the mucosal surface were altered or lacked cilia more frequently in the bronchial biopsies taken 24 h after the inhalation of histamine than in the control biopsies. In contrast, light and transmission electron microscopy revealed no increase in epithelial damage and no changes in the subepithelial morphology. The results indicate that inhalation of histamine does not significantly alter the structure of the bronchial mucosa, which means that bronchial biopsies can be taken for routine morphological examination within 24 h after a histamine test. When using the biopsies in research, one should consider the possible influence of the histamine test. PMID- 8457023 TI - Selenium supplementation in intrinsic asthma. AB - The accumulated data indicate that asthma is associated with reduced circulatory selenium (Se) status and lowered activity of the Se-dependent enzyme glutathione peroxidase (GSH-Px), which may have etiological implications, considering the important role of GSH-Px in the cellular elimination of hydroperoxides. The aim of the present double-blind study was to investigate whether Se supplementation in asthmatic patients may increase GSH-Px activity and possibly bring about clinical improvement. Twenty-four patients suffering from intrinsic asthma were selected and randomized into two groups, and after a preintervention period of 4 weeks, one group received a daily supplement of 100 micrograms sodium selenite for 14 weeks, whereas the other group received placebo. In the Se-supplemented group there were significant increases in serum Se and platelet GSH-Px activity after intervention, accompanied by a significant reduction in the irreversible platelet aggregation induced by 5 mumol/l ADP, while no significant changes in these parameters could be observed in the placebo group. Further, there was a significant clinical improvement in the Se-supplemented group, as compared with the placebo group, with regard to the assembled clinical evaluation made of each patient. This improvement could, however, not be validated by significant changes in the separate clinical parameters of lung function and airway hyperresponsiveness. The results are discussed in view of the role of GSH-Px in the cellular enzymatic oxidant defense system and as a modulator of arachidonic acid metabolism. PMID- 8457024 TI - T-cell and antibody response to Parietaria judaica allergenic fractions in atopic and nonatopic individuals. AB - The in vitro proliferative response to separated immunologically relevant components of Parietaria judaica pollen extract (PjE) was investigated by proliferation assay and limiting dilution analysis, in peripheral blood mononuclear cells from Parietaria-allergic subjects and nonallergic controls. In the same subjects, the profile of the antibody response to the PjE fractions was also studied by immunoblotting to evaluate the functional significance of allergen-induced T-cell activation in the two groups. The estimated frequency of PjE-reactive T cells in peripheral-blood mononuclear cells was low in both groups. No difference was found between the Parietaria-allergic subjects and nonallergic controls. To assess the overall contribution to the cellular response of PjE components of different molecular weights, we separated the extract by the SDS-PAGE technique, and the fractions were blotted onto nitrocellulose and solubilized. Almost all the 14 fractions tested induced T-cell proliferation, at different degrees of magnitude. Responses were similar in the allergic subjects and nonallergic controls. Immunoblotting demonstrated specific IgG antibodies to the 14 PjE fractions not only in the allergic subjects, but also in the healthy controls, whereas IgE antibodies were found, as expected, only in the sera from atopic subjects. These findings indicate that PjE fractions elicit similar T-cell activation and IgG production in allergic and normal subjects. PMID- 8457025 TI - Terbutaline controlled-release tablets and ipratropium aerosol in nocturnal asthma. AB - The effect of oral terbutaline (controlled-release [CR] tablets) was compared with that of inhaled ipratropium bromide (aerosol) in 21 patients with nocturnal asthma. In a randomized, double-blind, crossover study, the patients were treated with terbutaline CR 10 mg twice daily, ipratropium 40 micrograms four times daily, and the two drugs in combination. Each treatment was given for 3 weeks. Before the start of the study, the patients participated in a 1-week run-in period. The mean nocturnal decline in peak expiratory flow rate (PEFR) was 29% in the run-in period and was reduced to 22% in the terbutaline CR period, 27% in the ipratropium period, and 23% in the period with the combination of the two drugs. The mean night PEFR was significantly (P < 0.05) higher in the period with terbutaline CR, as compared with the period with ipratropium. The mean morning PEFR was also highest in the terbutaline CR period. The mean evening PEFR was significantly (P < 0.05) higher during treatment with terbutaline CR alone and with the combination, as compared with treatment with ipratropium alone. Treatment with terbutaline CR alone or the combination was preferred by as many patients as was treatment with ipratropium alone. When present, adverse reactions were judged to be mild or moderate. Treatment with terbutaline CR alone and the combination significantly improved the evening and night PEFR, as compared with treatment with ipratropium alone. PMID- 8457026 TI - Comparison of fiberglass-based histamine assay with a conventional automated fluorometric histamine assay, case history, skin prick test, and specific serum IgE in patients with milk and egg allergic reactions. AB - A microfiberglass-based histamine assay (HRM) was compared with an automated fluorometric histamine assay (HRA). Twenty-four subjects with and 24 without a case history (CH) of milk and/or egg allergy were tested by HRM and HRA, skin prick test (SPT), and specific serum IgE (RAST). Six different concentrations of milk, egg, and anti-IgE were used to stimulate washed leukocytes (250 microliters for HRA) and whole blood samples (25 microliters for HRM) in parallel. When we compared scores representing basophil sensitivity, correlation coefficients (rs) were positive (r(anti-IgE) = 0.88, r(egg) = 0.95, r(milk) = 0.88, P < 0.001), but no significant correlations were found after exclusion of the negatives in both tests. In some individual dose-response curves, the scores obtained by HRM were shifted to higher allergen and anti-IgE concentrations. A high degree of concordance was found in positive and negative responses between the two tests: anti-IgE 91%, egg 92%, milk 86%. Finally, we found a good concordance between, on one side, HRM and, on the other, CH, SPT, and RAST (HRM vs. CH/SPT/RAST): egg 92/82/82%; milk 89/74/67%. We conclude that HRM is in good qualitative, but poor quantitative, agreement with the autoanalyzer-based fluorometric histamine assay. PMID- 8457027 TI - Increase and decrease of delayed cutaneous reactions obtained by hypnotic suggestions during sensitization. Studies on dinitrochlorobenzene and diphenylcyclopropenone. AB - Cutaneous reactivity to challenge with dinitrochlorobenzene (DNCB) and diphenylcyclopropenone (DCP) was studied in 16 volunteers following hypnotic suggestions to increase and decrease response during sensitization. The immunoreactivity to DNCB and DCP was modulated by direct suggestions and guided imagery under hypnosis. The volunteers were highly susceptible subjects selected by means of the Harvard Group Scale of Hypnotic Susceptibility, Form A. Measurement of skin reactions to the challenge 1 month after sensitization was performed double blindly. Results showed a significant (P < 0.01) difference in visually scored reactions to DCP and DNCB between the group instructed to increase reaction to DCP and decrease reaction to DNCB and the group given the opposite instructions. A non-significant difference (P = 0.055) in skin thickness measured by ultrasound was found between the two groups. The study supports previous reports of experimental modulation of immunoreactivity and indicates that the specific immunological processes involved in the development of allergic reactions may be susceptible to psychological factors. PMID- 8457028 TI - Hypersensitivity to mustard seed. AB - Two patients were studied. Both underwent a thorough clinical evaluation, including a comprehensive physical examination. Both were also prick tested for inhalants, pollens, and food (including fruit). A nasal provocation test, serum immunoglobulins, total IgE serum, specific IgE serum, and a histamine release test were also carried out. The results of all these tests were positive to mustard seed. PMID- 8457029 TI - Is the use of contact lenses a risk factor for atopy? PMID- 8457030 TI - House-dust mites and associated environmental conditions in Danish homes. AB - The concentration of house-dust mites (Dermatophagoides pteronyssinus) was investigated in 96 Danish homes with one or more members suffering from asthma. The air-exchange rates, humidity, and temperature were measured in all the homes. A positive correlation was found between indoor air humidity and mite concentration (P < 0.01), and an inverse correlation (P = 0.027) between house dust mite concentration and indoor air-exchange was found. Homes of mite-allergic persons had a higher concentration of house-dust mites than did those of the non mite-allergic group. House-dust mite concentration was above the proposed limit of 10 mites/0.1 g dust in 76% of the homes of persons allergic to mites and in 48% of the homes of nonsensitive persons. The high proportion of homes infested with house-dust mites suggests an increased prevalence of house-dust mites in Danish homes. The results support the concept that reduced ventilation in homes involves a risk of increased house-dust mite exposure. PMID- 8457031 TI - Basidiomycete allergens: comparison of three Ganoderma species. AB - High atmospheric concentrations of basidiospores occur in various parts of the world. Ganoderma basidiospores are distinctive, easily identifiable in aeroallergen surveys, and widely abundant. Previous studies showed that Ganoderma basidiospores caused respiratory allergies. Thus, we investigated various extracts (spore, cap, and/or mycelial) of G. meredithae, G. lucidum, and G. applanatum for allergen components. Analyses included radioallergosorbent test (RAST) inhibition and IgE blots from isoelectric focusing (IEF) and SDS-PAGE. RAST inhibition with spores and caps of G. meredithae and G. lucidum showed that spores inhibited caps better than caps inhibited spores. Species differences were minor. Coomassie blue (CB) staining of IEF gels detected at least 23 protein bands (pI 3.6-6.6) in caps of G. meredithae and G. lucidum. G. meredithae spore extracts contained 17 of these (pI 3.6-5.0, 6.6). Spores and caps of G. meredithae contained 13 and 11 allergen bands, respectively, on IEF blots. SDS PAGE of G. meredithae spore and cap showed one and four bands, respectively, by CB staining, but IgE blots showed 13 bands in cap and 17 in spore. Culture mycelia of G. lucidum and G. applanatum attained significant and essentially constant RAST activity by day 4. Activity was also present in culture supernatant by day 4. Blots of mycelium and supernatant detected a single allergen in day-8 mycelia and subsequently six allergen bands in day-16 mycelia and eight in day-16 supernatant (one appeared as a doublet). These data show that Ganoderma extracts contain a complex mixture of allergens. Differences among species were minor; spores and mycelia are apparently better sources of allergens than caps. PMID- 8457032 TI - Methacholine reactivity and asthma. Report from the Northern Sweden Obstructive Lung Disease Project. AB - Methacholine tests were used in an epidemiologic study of the prevalence of asthma and chronic bronchitis in northern Sweden. Of 6610 subjects in three age groups from eight representative geographic areas in the northernmost province of Sweden, 5698 (86%) completed a postal questionnaire on respiratory symptoms, and 1506 underwent a structured interview and a lung function test. A total of 292 (5%) were diagnosed as having asthma. A subsample of 284 subjects (of 320 invited) classified at the interview as having asthma (n = 98) or as having respiratory symptoms that might be due to asthma but not fulfilling the interview criteria for the diagnosis of asthma (n = 186) underwent a methacholine test. Subjects who, before the interview study, already had a well-defined asthma diagnosis were not invited to the methacholine testing. Of those 98 subjects classified as having asthma, 61% reacted to methacholine doses < or = 4 mg/ml and 79% to doses < or = 8 mg/ml, while the corresponding figures in the symptomatic but nonasthma group were 20% and 34%, respectively. The results show that a carefully performed structured interview accurately diagnoses asthma in epidemiologic studies. The methacholine tests provide important diagnostic information primarily in subjects in whom the medical history is equivocal. PMID- 8457033 TI - Associated sensitization to latex and chestnut. PMID- 8457034 TI - The discovery of IgE. PMID- 8457035 TI - Tryptase in nasal fluid is a useful marker of allergic rhinitis. AB - Tryptase is a mast cell-specific marker of degranulation. To investigate the possible diagnostic value of tryptase in allergic rhinitis, we measured the levels in both serum and native nasal fluid with a sandwich RIA-assay (Pharmacia). Twenty-three allergic patients and five patients with chronic ethmoidal sinusitis were included. Eighteen of the 23 allergic patients were tested within the pollen season or had perennial rhinitis; the remainder were tested at least 1 month out of the pollen season. None of the patients had detectable serum tryptase (> 0.1 ng/ml). Also patients with chronic ethmoidal sinusitis showed no tryptase in nasal fluid. One of seven allergic patients tested out of season had slightly increased nasal tryptase of 1.8 ng/ml. In patients with active nasal allergy, the tryptase in nasal fluid ranged from 6.4 ng/ml to 640 ng/ml with a mean of 101 ng/ml and SD 173. These results show a clear distinction between active and non-active nasal allergy and other non-mast cell-related nasal disease. Further, nasal tryptase release by natural allergen exposure is even higher than that observed in allergen challenge tests. PMID- 8457036 TI - Gamma-interferon production in cow milk allergy. AB - The aim of this study was to develop an assay to assist in the diagnosis of delayed onset of adverse responses to cow milk in children, by measurement of gamma-interferon (GIFN) produced in vitro in response to beta-lactoglobulin stimulated blood mononuclear cells. Diagnostic procedures identified 75 children with immediate reactions who had high total IgE and IgE-isotype responses to cow milk, 17 children who developed reactions after 24 h and had low total IgE and low IgE-isotype response to cow milk, and 59 milk-tolerant children. GIFN production was less in children with immediate reactions compared to those with late reactions (P < 0.009), or milk-tolerant children (P = 0.022). The results of this study suggest enhanced T-cell reactivity may be involved in the immuno pathogenesis of non-immediate cow milk allergy, but GIFN production was not a clinically useful diagnostic test. PMID- 8457037 TI - Immunotherapy with aluminum hydroxide adsorbed insect venom extracts (Alutard SQ): immunologic and clinical results of a prospective study over 3 years. AB - This prospective study over 3 years investigated the safety, immunogenicity, and effectiveness of immunotherapy (IT) with aluminum hydroxide adsorbed insect venom extracts (Alutard SQ, ALK Laboratories) in patients with previous, severe, systemic, IgE-mediated, anaphylactic reactions to Hymenoptera stings. Seventeen patients were treated with honeybee venom (BV), 13 with yellow-jacket venom (YJV), and 5 with both. No severe reactions to IT were noted. Only 3 BV-allergic patients experienced mild systemic reactions of grades I or II (1 per 139 injections) during the increase phase. As for the immunologic data, there was a significant decrease in specific IgE antibodies after 1 year, and a significant increase in specific IgG and IgG4 antibodies on reaching the maintenance dose, with a further rise after 1, 2, and 3 years. Moreover, a significant decrease in anti-IgE autoantibodies was observed in the BV group. Out of the 11 patients that were occasionally restung by the relevant insect (totaling 19 stings in all), only one patient developed mild systemic allergic symptoms after a third sting. In view of these results, we consider IT with aluminum hydroxide adsorbed insect venom extracts to be safe, immunogenic, and effective. The low rate of side effects may be due to the slow release of the venom in the aluminum hydroxide adsorbed form. PMID- 8457038 TI - Early and late nasal symptom response to allergen challenge. The effect of pretreatment with a glucocorticosteroid spray. AB - We challenged 30 pollen-sensitive volunteers with allergen, recorded symptoms and signs over a 10-h period, and rechallenged them after 24 h, in order to characterize the early and late allergic symptom response in the nose. The challenge was performed after topical pretreatment with the glucocorticosteroid budesonide (200 micrograms twice daily) for 14 d and with placebo in a double blind, cross-over trial. The early response, consisting of sneezing, discharge, and blockage, was followed by a weak late response, consisting of a few sneezes and nose-blowings, and of a sustained nasal blockage. These symptoms did not have a well-defined peak in time, and a biphasic symptom curve could not be identified. The rechallenge response showed increased nasal responsiveness. The degree of budesonide effect on the early response varied, depending on the symptom; there was a marked effect on sneezing (72% reduction; P < 0.01), a moderate effect on discharge (37% reduction; P < 0.01), and a slight effect on blockage (17% reduction of nasal inspiratory peak flow rate; P < 0.02). The degree of inhibition of the rechallenge response was similar to the effect on the initial early response. The effect on the late response was very pronounced for all symptoms and signs (97% reduction of sneezes, 76% reduction of nose-blowings, 96% reduction of blockage; P < 0.01). In conclusion, we found it difficult in the individual subject to identify a well-defined late symptom response by criteria similar to those employed to characterize the late response in the bronchi. The effect of budesonide was more marked on sneezing than on blockage, and the drug was considerably more effective on the late response than on the early response. PMID- 8457039 TI - A new method of counting airborne Japanese cedar (Cryptomeria japonica) pollen allergens by immunoblotting. AB - We have devised a new method of counting pollen allergen particles, modified from the fluorescent immunoblotting technique of Schumacher et al. Airborne Japanese cedar pollen allergens collected on Burkard's sampling tape were transferred onto a nitrocellulose membrane. The membrane was then treated with antiallergen mouse monoclonal antibody conjugated with alkaline phosphatase. Pollen allergens were detected as purple spots on the nitrocellulose membrane after phosphate substrate staining was performed. Pollen allergen particles were visible under a stereoscopic microscope or to the naked eye and could thus be counted easily. This new counting method takes less time than previous methods and requires no special skill. PMID- 8457040 TI - A comparative study of the characteristics of intraepithelial and lamina propria lymphocytes of the human nasal mucosa. AB - The phenotypes and receptors of the intraepithelial lymphocytes which are a major component of the mucosal immune system are of considerable interest. Intraepithelial lymphocytes, especially those of the intestines, are well documented. The nasal intraepithelial lymphocytes probably play a key role in the immune defense of the entire respiratory tract. However, documentation of these lymphocytes is limited to only a few nondescriptive studies by immunohistological methods. In our previous paper, we examined the subsets of the nasal intraepithelial lymphocytes by two-color flow cytometry after culture with monoclonal antibody against CD3 and PMA. The mucosal immune system, which comprises the lymphoid tissue associated with the mucosal surface, consists of lymphocyte populations from both the epithelium and the lamina propria. In this paper (a sequel to our previous study), we have carried out a comparative study of the intraepithelial lymphocytes and lamina propria lymphocytes of the human nasal mucosa. In the 42 patients (with allergic rhinitis/infectious hypertrophic rhinitis) whom we examined, T lymphocytes were predominant in the epithelium as well as the lamina propria. B lymphocytes were detected only in the lamina propria. CD8+ T cells (suppressor/cytotoxic) and CD4-8- (double-negative) (DN) comprised the major population of the intraepithelial lymphocytes. The CD4+/CD8+ ratio was 0.5 +/- 0.1. In contrast, the lamina propria showed a predominance of CD4+ T cells (helper/inducer), with a CD4+/CD8+ ratio of 1.3 +/- 0.2. CD3 + 4-8- (double-negative T cells) were comparable in number in the epithelium and the lamina propria. CD8+ T cells of the epithelium were predominantly cytotoxic T cells, and CD4+ T cells were predominantly helper T cells. In the lamina propria, CD8+ T cells were predominantly of the suppressor type.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457041 TI - Inhaled nitric oxide. The past, the present, and the future. PMID- 8457042 TI - The quest for meaningful outcomes. PMID- 8457043 TI - Inhaled nitric oxide selectively reverses human hypoxic pulmonary vasoconstriction without causing systemic vasodilation. AB - BACKGROUND: Nitric oxide (NO), an endothelium-derived relaxing factor, acts as a local vasodilator. The authors examined the effects of NO on pulmonary and systemic circulation in human volunteers. METHODS: Nine healthy adults were studied awake while breathing 1) air, 2) 12% O2 in N2, 3) followed by the same mixture of O2 and N2 containing 40 ppm of NO. Pulmonary artery and radial artery pressures were monitored. RESULTS: The PaO2 decreased from 106 +/- 4 (mean +/- standard error of the mean) while breathing air (21% O2) to 47 +/- 2 mmHg after 6 min of breathing 12% O2. Concomitantly, the pulmonary artery mean pressure (PAP) increased from 14.7 +/- 0.8 mmHg to 19.8 +/- 0.9 mmHg, and the cardiac output (CO) increased from 6.1 +/- 0.4 to 7.7 +/- 0.6 L/min. After adding 40 ppm NO to the inspired gas while maintaining the FIO2 at 0.12, the PAP decreased (P < 0.01, by analysis of variance) to the level when breathing air while the PaO2 and PaCO2 were unchanged. The dilation (or recruitment) of pulmonary vessels produced by inhaling NO during hypoxia was not accompanied by any alteration in the systemic vascular resistance or mean arterial pressure (MAP). The authors also examined the effects of inhaling NO while breathing air. Breathing 40 ppm NO in 21% O2 for 6 min produced no significant changes of PAP, CO, PaO2, MAP, or central venous pressure. Plasma endothelinlike immunoreactivity concentrations did not change either during hypoxia or hypoxia with NO inhalation. CONCLUSIONS: Inhalation of 40 ppm NO selectively induced pulmonary vasodilation and reversed hypoxic pulmonary vasoconstriction in healthy humans without causing systemic vasodilation. PMID- 8457044 TI - Randomized evaluation of pulse oximetry in 20,802 patients: I. Design, demography, pulse oximetry failure rate, and overall complication rate. AB - BACKGROUND: Although pulse oximetry is currently in widespread use, there are few data documenting improvement in patient outcome as a result of the use of oximetry. The authors describe the study design, patient demographic findings, data validation, pulse oximetry failure rate, and overall postoperative complication rates in the first large prospective randomized multicenter clinical trial on perioperative pulse oximetry monitoring. METHODS: In five Danish hospitals, by random assignment, monitoring did or did not include pulse oximetry for patients 18 yr of age and older, whether scheduled for elective or emergency operations, or for regional or general anesthesia, except during cardiac and neurosurgical procedures. Operational definitions were established for perioperative events and postoperative complications. The data were collected preoperatively, during anesthesia, in the postanesthesia care unit, and until the day of discharge from the hospital or the seventh postoperative day. RESULTS: Of 20,802 patients, 10,312 were assigned to the oximetry group and 10,490, to the control group. In general, the demographic data, patient factors, and anesthetic agents used were distributed evenly. A slight intergroup difference was found in the distribution of age, duration of surgery, some types of surgery, and some types of anesthesia. The total failure rate of the oximetry was 2.5%, but it increased to 7.2% in patients with American Society of Anesthesiologists physical status 4 (P < 0.00001). In 14.9% of the patients, one or more events occurred in the operating room and 13.5% in the postanesthesia care unit. The overall postoperative complication rate was 9.7%. The total rates of cardiovascular and respiratory complications were 2.78% and 3.50%, respectively. Within the first seven postoperative days, 0.47% of the patients died. Anesthesia was not thought to have been solely responsible for any death, but in 7 patients (1 per 3,365), it was a possible contributory factor. CONCLUSIONS: Despite the finding of a few significant inter-group differences, the randomization was well balanced with a high validity of data. The overall postoperative complication rate was similar to that in other recent morbidity and mortality studies. PMID- 8457045 TI - Randomized evaluation of pulse oximetry in 20,802 patients: II. Perioperative events and postoperative complications. AB - BACKGROUND: The authors describe the effect of pulse oximetry monitoring on the frequency of unanticipated perioperative events, changes in patient care, and the rate of postoperative complications in a prospective randomized study. METHODS: The study included 20,802 surgical patients in Denmark randomly assigned to be monitored or not with pulse oximetry in the operating room (OR) and postanesthesia care unit (PACU). RESULTS: During anesthesia and in the PACU, significantly more patients in the oximetry group had at least one respiratory event than did the control patients. This was the result of a 19-fold increase in the incidence of diagnosed hypoxemia in the oximetry group than in the control group in both the OR and PACU (P < 0.00001). In the OR, cardiovascular events were observed in a similar number of patients in both groups, except myocardial ischemia (as defined by angina or ST-segment depression), which was detected in 12 patients in the oximetry group and in 26 patients in the control group (P < 0.03). Several changes in PACU care were observed in association with the use of pulse oximetry. These included higher flow rate of supplemental oxygen (P < 0.00001), increased use of supplemental oxygen at discharge (P < 0.00001), and increased use of naloxone (P < 0.02). The rate of changes in patient care as a consequence of the oximetry monitoring increased as the American Society of Anesthesiologists physical status worsened (P < 0.00001). One or more postoperative complications occurred in 10% of the patients in the oximetry group and in 9.4% in the control group (difference not significant). The two groups did not differ significantly in cardiovascular, respiratory, neurologic, or infectious complications. The duration of hospital stay was a median of 5 days in both groups (difference not significant). An equal number of inhospital deaths were registered in the two groups. Questionnaires, completed by the anesthesiologists at the five participating departments, revealed that 18% of the anesthesiologists had experienced a situation in which a pulse oximeter helped to avoid a serious event or complication and that 80% of the anesthesiologists felt more secure when they used a pulse oximeter. CONCLUSIONS: This study demonstrated that pulse oximetry can improve the anesthesiologist's ability to detect hypoxemia and related events in the OR and PACU and that the use of the oximeter was associated with a significant decrease in the rate of myocardial ischemia. Although monitoring with pulse oximetry prompted a number of changes in patient care, a reduction in the overall rate of postoperative complications was not observed. PMID- 8457046 TI - Effects of fentanyl versus sufentanil in equianesthetic doses on middle cerebral artery blood flow velocity. AB - BACKGROUND: Sufentanil has been reported to increase cerebral blood flow in comparison with fentanyl. However, because of the use of animal models, supraclinical doses and/or background anesthetic agents, the clinical applicability of these studies remains difficult to assess. Therefore, transcranial Doppler ultrasonography was used to determine the cerebral hemodynamic effects of equianesthetic doses of fentanyl and sufentanil on middle cerebral artery (MCA) blood flow velocity in patients without intracranial pathologic conditions. METHODS: Twenty-four unpremedicated American Society of Anesthesiologists physical status 1 and 2 patients undergoing elective nonintracranial neurosurgery were assigned randomly to receive equipotent blinded infusions of either sufentanil (15 micrograms/min) or fentanyl (150 micrograms/min) for anesthetic induction during spontaneous ventilation of 100% oxygen. Normocapnia, as measured by infrared capnography, was maintained by manually assisting ventilation, as necessary. The cerebral opioid effect was quantified using the spectral edge frequency parameter. The infusion was continued until either 1) spectral edge frequency decreased below 10 Hz or 2) 150 micrograms of sufentanil or 1,500 micrograms of fentanyl was infused, whichever occurred first. On average, the patients received 1.7 +/- 0.55 micrograms/kg or 16 +/- 4 micrograms/kg of sufentanil or fentanyl, respectively. The right MCA mean, peak systolic, and peak diastolic velocities and pulsatility index were measured continuously by transcranial Doppler ultrasonography. RESULTS: The mean arterial pressure decreased slightly in both groups, but only in the fentanyl group were the changes significant. The MCA velocity increased by approximately 25% in both groups. However, the relative changes in MCA velocity were not different between groups. The pulsatility indexes were unchanged in both groups. CONCLUSIONS: These data suggest that, at clinically relevant doses in the absence of other drugs, cerebral blood flow velocity is increased by both fentanyl and sufentanil. Furthermore, there appears to be no significant differences in the cerebral hemodynamic profiles of the two drugs, as assessed by transcranial Doppler ultrasonography. PMID- 8457047 TI - Unintentional hypothermia is associated with postoperative myocardial ischemia. The Perioperative Ischemia Randomized Anesthesia Trial Study Group. AB - BACKGROUND: Hypothermia occurs commonly during surgery and can be associated with increased metabolic demands during rewarming in the postoperative period. Although cardiac complications remain the leading cause of morbidity after anesthesia and surgery, the relationship between unintentional hypothermia and myocardial ischemia during the perioperative period has not been studied. METHODS: One hundred patients undergoing lower extremity vascular reconstruction received continuous Holter monitoring throughout the first 24 h postoperatively. Myocardial ischemia was determined by a cardiologist masked to clinical variables. The patient's sublingual temperature on arrival at the intensive care unit immediately after the surgical procedure was used to divide the patients into two groups: hypothermic (temperature, < 35 degrees C; n = 33) and normothermic (temperature, > or = 35 degrees C; n = 67). The relationship between intentional hypothermia and myocardial ischemia occurring during the first postoperative day was evaluated by univariate and multivariate analyses. RESULTS: A greater percentage of patients had electrocardiographic changes consistent with myocardial ischemia in the hypothermic group (36%, 12 of 33) compared with those in the normothermic group (13%, 9 of 67, P = 0.008). Preoperative risk factors for perioperative cardiac morbidity were similar between the two groups, except for patient age. The mean age was 70 +/- 2 yr and 62 +/- 1 yr in the hypothermic and normothermic groups, respectively (P = 0.001). When subgroup and multivariate analyses were used to adjust for differences in age, temperature remained an independent predictor of ischemia (odds ratio, 1.82 per degree Celsius; 95% confidence interval, 1.09-3.02). The incidence of postoperative angina was greater in the hypothermic group (18%, 6 of 33) than in the normothermic group (1.5%, 1 of 67, P = 0.002). The incidence of PaO2 < 80 mmHg in the arterial blood was greater in the hypothermic group (52%, 17 of 33) than in the normothermic group (30%, 20 of 67, P = 0.03). CONCLUSIONS: Unintentional hypothermia is associated with myocardial ischemia, angina, and PaO2 < 80 mmHg during the early postoperative period in patients undergoing lower extremity vascular surgery. PMID- 8457048 TI - Automated real-time analysis of intraoperative transesophageal echocardiograms. AB - BACKGROUND: Although transesophageal echocardiography (TEE) produces real-time images depicting left ventricular (LV) filling and ejection, the quantitative analysis of these images has been too time consuming to be of practical value in the operating room. Therefore, the authors investigated whether a new automated border detection system (ABD) could track the endocardial border continuously and compute the cross-sectional area of the LV cavity. METHODS: Using data from 25 patients who were monitored with TEE as part of their routine clinical care, the authors compared ABD estimates of LV end-diastolic area (EDA in square centimeters), end-systolic area (ESA in square centimeters), and fractional area change (FAC) with the laboratory measurements made independently by an expert. RESULTS: ABD slightly underestimated EDA (10.7 +/- 1.0 vs. 11.2 +/- 1.0 cm2) and slightly overestimated ESA (5.6 +/- 0.7 vs. 4.8 +/- 0.6 cm2, mean +/- standard error). However, when ABD tracking of the endocardial border was judged as "good" or "excellent" (84% of the patients at end diastole and 72% at end systole), the limits of agreement between ABD and the expert's findings were within the limits expected for two experts. By contrast, ABD significantly underestimated FAC (0.44 +/- 0.03 vs. 0.56 +/- 0.03) and the limits of agreement between ABD and the expert were more than twice as great as expected for experts, even when ABD performance was judged as "excellent." CONCLUSION: The authors conclude that, when ABD appears to be performing adequately, it underestimates LV FAC, but provides valid real-time estimates of LV EDA and ESA. Thus, it warrants further evaluation as a potentially powerful clinical and research tool. PMID- 8457049 TI - Postcesarean delivery epidural patient-controlled analgesia. Fentanyl or sufentanil? AB - BACKGROUND: The highly lipid-soluble opioids, fentanyl and sufentanil, frequently are used in combination with local anesthetic agents and/or epinephrine to provide postoperative epidural analgesia. The authors compared the incidence of side effects and patient satisfaction during prolonged epidural patient controlled analgesia (PCA) infusions of these opioids in combination with bupivacaine and epinephrine. METHODS: Using a double-blind study design, 250 patients scheduled for elective cesarean delivery were, on arrival in the postanesthesia care unit, randomized into two epidural PCA infusion groups: group I (n = 125) received fentanyl 2 micrograms/ml with bupivacaine 0.01% and epinephrine 0.5 micrograms/ml and group II (n = 125) received sufentanil 0.8 micrograms/ml with bupivacaine 0.01% and epinephrine 0.5 microgram/ml. The initial infusion rate was 16 ml/h with self-administered 3-ml boluses every 15 min by PCA as desired. At intervals after discontinuation of the infusion, plasma samples were obtained to determine opioid concentrations. RESULTS: The median overall satisfaction scores were 9.0 for group I and 10.0 for group II (difference not significant). Pain relief was satisfactory and comparable in both groups, and all patients could ambulate easily. The total number of times PCA requests were made was greater (P < 0.05, by Wilcoxon rank-sum test) for group I than for group II (106.7 +/- 312 vs. 70.8 +/- 138). There were no differences between the groups with respect to incidence of pruritus, sedation, and nausea; however, vomiting occurred more frequently with sufentanil than with fentanyl (12% vs. 4.8%, respectively; P < 0.05). At approximately 1-2 h after discontinuation of the infusion, 1 patient receiving fentanyl and 42 patients receiving sufentanil complained of lightheadedness and dizziness (P < 0.0001). CONCLUSIONS: Epidural PCA in both groups had no serious side effects and achieved a high level of patient satisfaction. Those receiving sufentanil made fewer PCA requests but had a significantly greater incidence of vomiting during the infusion and dizziness after the termination of the infusion. Epidural sufentanil offered no advantages over epidural fentanyl. PMID- 8457050 TI - Back pain after epidural anesthesia with chloroprocaine. AB - BACKGROUND: Chloroprocaine has been associated with severe back pain after epidural anesthesia. Factors proposed to contribute to this problem are: 1) the preservative disodium ethylenediaminetetraacetic acid (EDTA), 2) large volumes of chloroprocaine, 3) low pH of chloroprocaine, and 4) local infiltration with chloroprocaine. METHODS: Using a prospective, balanced, randomized study design, 100 patients aged 18-65 yr who were undergoing outpatient knee surgery during continuous epidural anesthesia received one of five local anesthetics (all containing epinephrine 1:200,000). Group I received a bolus of 30 ml 2% lidocaine, followed by 10 ml every 45 min. Group II received 15 ml of 3% chloroprocaine (containing EDTA), plus 5 ml every 45 min. Group III received 30 ml of 3% chloroprocaine plus 10 ml every 45 min. Group IV received 30 ml of 3% chloroprocaine (containing metabisulfite as the preservative but no EDTA) plus 10 ml every 45 min. Group V received 30 ml of 3% chloroprocaine with the pH adjusted to 7.3, plus 10 ml every 45 min. After the anesthesia dissipated and before any analgesic agents were given, the patients were asked to rank maximum knee and back pain on a visual analog scale (0-10) and to give a description of back pain. A telephone interview was conducted 24 h after surgery to determine if back pain returned. Back pain scoring was assessed using a verbal analog scale. RESULTS: After dissipation of anesthesia, the back pain reported by patients fell into two distinct categories. Type 1 pain was described commonly as superficial and localized to the site of needle insertion. There was no difference among groups in incidence of type 1 pain. Type 2 pain was described as deep, aching, burning, and poorly localized in the lumbar region (5% of the patients in group I, 10% in groups II and IV, 50% in group III, and 25% in group V). The incidence of type 2 pain was significantly greater in group III than in groups I, II, or IV. Group III also had a significantly greater mean visual analog scale pain score (types 1 and 2) than all other groups. CONCLUSIONS: Large doses (> or = 40 ml) of chloroprocaine containing EDTA resulted in a greater incidence of deep burning lumbar back pain. Using 25 ml or less of the same solution resulted in an incidence of both types 1 and 2 postepidural anesthesia back pain similar to that in the lidocaine control group. PMID- 8457051 TI - The P3a wave of the auditory event-related potential reveals registration of pitch change during sufentanil anesthesia for cardiac surgery. AB - BACKGROUND: The N1 and P3 waves of the auditory event-related potential provide information on consciousness and cortical function. The N1 wave is reduced during states of low vigilance. The P3 wave occurs only for stimuli that somehow capture the subject's attention. There are two types of P3:P3a and P3b. The P3a predominates frontally and probably occurs when the subject simply notices the stimulus. The P3b predominates parietally and indicates conscious awareness of the evoking stimulus. The N1 and P3 were recorded in 12 patients during cardiac surgery under sufentanil anesthesia to search for unintentional awareness. The study was limited to the period before cardiopulmonary bypass. METHODS: After premedication with diazepam, morphine, and scopolamine, sufentanil was used for induction (mean dose, 7.9 micrograms/kg) and maintenance (4 micrograms/kg) of anesthesia. No other anesthetics were administered. Recordings were obtained before induction, during induction after loss of consciousness, after tracheal intubation before incision, and before cardiopulmonary bypass. RESULTS: The N1 was attenuated significantly by sufentanil but was not abolished. The P3b occurred only during preinduction. There was no P3 during induction. There was a P3a during postintubation and precardiopulmonary bypass. CONCLUSIONS: The attenuation of N1 from induction onward reflects a decrease in the level of arousal caused by sufentanil. A P3a during postintubation and precardiopulmonary bypass indicates that pitch discrimination at the cortical level occurs but does not prove that conscious awareness has occurred. Whether or not the P3a reflects the regaining of consciousness is not known. PMID- 8457052 TI - Transmural redistribution of myocardial blood flow during isoflurane anesthesia and its effects on regional myocardial function in a canine model of fixed coronary stenosis. AB - BACKGROUND: The effects of isoflurane on the transmural distribution of myocardial blood flow distal to an acute critical coronary stenosis and the relationship between the changes in regional blood flow and function were studied to determine whether isoflurane can produce a transmural "steal" phenomenon and to assess the role of this phenomenon in producing changes in regional myocardial function. METHODS: After production of acute critical coronary stenosis under baseline chloralose and fentanyl anesthesia, the animals were exposed to increasing end-tidal concentrations of isoflurane (0.7%, 1.4%, and 2.1%) without control of the hemodynamic parameters. At 2.1% isoflurane, the blood pressure then was restored to the baseline level by administration of phenylephrine. Changes in the following parameters were assessed: global contractility (measured by changes in pressure with time), regional myocardial function (assessed by systolic wall thickening and measured by sonomicrometers), transmural distribution of myocardial perfusion (measured by the radioactive microsphere method), and regional oxygen consumption and extraction. RESULTS: Distal to the critical stenosis, a transmural redistribution of myocardial blood flow (endocardial-epicardial ratio < 1) occurred with all concentrations of isoflurane. With higher concentrations (1.4% and 2.1%), a significant decrease in subendocardial blood flow occurred only in the presence of hemodynamic changes and was restored by phenylephrine. In this area, changes in regional myocardial function correlated most strongly with changes in subendocardial perfusion (y = 0.17 + 1.70x -0.58x2, r2 = 0.90). In the stenotic region, oxygen extraction remained stable, but oxygen consumption decreased in parallel with reductions in regional myocardial function. In the normal region, oxygen consumption did not change, but oxygen extraction decreased with increasing isoflurane concentrations. CONCLUSIONS: These results show that isoflurane is a coronary vasodilator able to induce a transmural redistribution of myocardial blood flow distal to an acute critical coronary stenosis. A true transmural steal, however, was not produced reliably in the absence of hemodynamic changes, suggesting that isoflurane either is only a moderate vasodilator, or that the decrease in subendocardial blood flow is offset by the negative inotropic action of the drug. When regional myocardial dysfunction distal to a severe coronary stenosis occurs, this correlates with decreasing subendocardial blood flow during isoflurane anesthesia, suggesting ischemia as the cause. PMID- 8457053 TI - Effects of halothane on global and regional biventricular performances and on coronary hemodynamics before and during right coronary artery stenosis in the dog. AB - BACKGROUND: Previously, it was suggested that right ventricular (RV) free wall dysfunction does not necessarily elicit global hemodynamic alterations. This was investigated in a canine model of halothane-induced right coronary artery (RCA) insufficiency. METHODS: Two concentrations (0.8% and 1.6% end tidal) of halothane on global and regional RV and left ventricular (LV) performance and on coronary, pulmonary, and systemic hemodynamics were studied in 10 open-chest dogs first before and, subsequently, during critical RCA stenosis. RESULTS: In the absence of stenosis, halothane caused progressive and comparable depression of regional and global RV and LV function and reduction of RCA flow. Halothane administered during RCA stenosis caused disproportionate decreases in RCA flow and segment shortening and increases in systolic segment lengths in the area supplied by the stenosed RCA that were approximately twice as great as before stenosis. Such severe regional RV dysfunction was not accompanied by greater depression of global RV and LV pump function (systolic pressures and stroke volume). CONCLUSIONS: In the canine heart with its dominant left coronary system, RCA insufficiency (on the basis of halothane-induced hypotension) caused regional RV dysfunction suggesting ischemia that was not accompanied by global hemodynamic alteration. PMID- 8457054 TI - Altered release and metabolism of norepinephrine in superfused canine saphenous veins in the presence of halothane and hypoxia. AB - BACKGROUND: Hypoxia and halothane are both known to have different effects on the release and disposition of norepinephrine at sympathetic nerve terminals during neurotransmission. In adverse clinical situations, both conditions may be present, but the effects of halothane and hypoxia together are not known. Therefore, studies were made of the effects of low partial pressures of oxygen and of halothane on the release, action, and metabolism of norepinephrine at sympathetic nerve endings in isolated segments of a blood vessel in which halothane is known to affect norepinephrine release and action profoundly. METHODS: Saphenous veins were removed from dogs, suspended for superfusion with Krebs-Ringer solution, and stimulated electrically. The veins were exposed to either 0%, 0.75%, or 1.5% halothane in the presence of 95% O2, 5% CO2, or 5% O2, 5% CO2, and 90% N2. Superfusates were collected under basal conditions, during and after electrical field stimulation, and poststimulation. Norepinephrine and its intraneuronal metabolite, 3,4-dihydroxyphenylglycol, were measured in superfusates and in the tissues after superfusion using high-performance liquid chromatography with electrochemical detection. RESULTS: Halothane decreased 1) evoked release of norepinephrine, 2) contractile response of the smooth muscle to nerve stimulation, 3) formation of 3,4-dihydroxyphenylglycol, and 4) tissue content of norepinephrine. However, hypoxia 1) increased evoked release of norepinephrine but decreased 2) contractile response during nerve stimulation, 3) formation of 3,4-dihydroxyphenylglycol, and 4) tissue content of norepinephrine. When halothane and hypoxia were present together, their effects on 3,4 dihydroxyphenylglycol formation, tissue content of norepinephrine, and the contractile responses appeared to be additive, but norepinephrine release was decreased compared with control concentrations. CONCLUSIONS: Although halothane and hypoxia had similar and additive effects on the intraneuronal metabolism of norepinephrine and on the postjunctional responses of smooth muscle to nerve stimulation, they had opposite effects on norepinephrine release from sympathetic nerve endings. The halothane-induced decrease in norepinephrine release overrode the increased release of norepinephrine caused by hypoxia. PMID- 8457055 TI - Effects of propofol and thiopental on maternal and fetal cardiovascular and acid base variables in the pregnant ewe. AB - BACKGROUND: The effects of propofol on uterine blood flow are not understood well. This is a relatively new agent that is finding increased use for nonobstetric surgical procedures during pregnancy and induction of anesthesia for cesarean section. METHODS: The effects of induction and maintenance of anesthesia with propofol were studied on maternal and fetal cardiovascular and acid-base variables in a chronically instrumented pregnant sheep model. Anesthesia was induced with a 2 mg/kg bolus of propofol and maintained with of one of three continuous infusions: 150, 300, and 450 micrograms.kg-1 x min-1. The control group received thiopental for induction, and anesthesia was maintained with isoflurane. RESULTS: The use of propofol did not adversely affect maternal or fetal mean arterial pressure, heart rate, or base excess, fetal heart rate variability, or uterine blood flow. Uterine blood flow transiently decreased during induction and intubation with thiopental but remained stable during induction with propofol. However, administration of succinylcholine for intubation in the presence of propofol resulted in a transient, but severe, maternal bradycardia. Continuous infusion of 300 micrograms.kg-1.min-1 of propofol appeared to provide satisfactory anesthesia in the ewe. CONCLUSIONS: Assuming the applicability of ovine data to humans, these findings suggest that induction and maintenance of anesthesia with propofol and 50% nitrous oxide in oxygen has no adverse fetal effects but warrants caution because of the potential risk of severe maternal bradycardia during induction of anesthesia using the combination of propofol and succinylcholine. PMID- 8457056 TI - Inhalation of nitric oxide reduced pulmonary hypertension after cardiac surgery in a 3.2-kg infant. PMID- 8457057 TI - Neurologic deterioration associated with airway management in a cervical spine injured patient. PMID- 8457058 TI - Liquid full nitrous oxide cylinders. PMID- 8457059 TI - Ischemic complications of radial artery cannulation: an association with a calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia variant of scleroderma. PMID- 8457060 TI - Streptococcus mitis-induced bacteremia and meningitis after spinal anesthesia. PMID- 8457061 TI - Acute arterial insufficiency of the upper extremity after central venous cannulation. PMID- 8457062 TI - Practice guidelines for management of the difficult airway. A report by the American Society of Anesthesiologists Task Force on Management of the Difficult Airway. PMID- 8457063 TI - Ventilation via a mouth mask facilitates fiberoptic nasal tracheal intubation in anesthetized patients. PMID- 8457064 TI - Pharmacodynamics of propofol and free drug concentrations. PMID- 8457065 TI - Were they subdural injections? PMID- 8457066 TI - Secondary sharps container. PMID- 8457067 TI - Do barbiturates really protect the brain? PMID- 8457068 TI - A better citation system. PMID- 8457069 TI - On the importance of inaccurate bibliographic citations. PMID- 8457070 TI - Accuracy in reference citations. PMID- 8457071 TI - A new method of endotracheal tube fixation for pediatric neurosurgical patients. PMID- 8457072 TI - Use of a dental mirror as an aid to tracheal intubation in an infant. PMID- 8457073 TI - Increased intracranial pressure in head trauma patients given fentanyl or sufentanil. PMID- 8457074 TI - Fentanyl and sufentanil increase intracranial pressure in head trauma patients. PMID- 8457075 TI - Reducing syringe swap errors. PMID- 8457076 TI - Cardiac depressant effects of oxygen free radicals. AB - In many clinical situations, including cardiac ischemia/reperfusion, elective cardiac arrest, and renal dialysis, the chances of increased production of oxygen free radicals (OFR) exist. OFR have been implicated as a causative factor of cell damage in several pathologic conditions. The effects of exogenous OFR, generated by xanthine plus xanthine oxidase, in the absence and in the presence of OFR scavenger (superoxide dismutase [SOD]) on the contractility of isolated perfused heart of rabbit were studied. OFR produced concentration-dependent decreases in the contractility of perfused heart. SOD prevented the OFR-induced decreases in the left ventricular contractility. Xanthine produced an increase in the contractility of isolated perfused rabbit's heart. Xanthine oxidase produced a marked decrease in the left ventricular contractility. Repeated administration of xanthine oxidase produced accelerated and greater decreases in the contractility of perfused heart when compared with that of the initial administration of the drug. Effects of xanthine or xanthine oxidase on the cardiac function and contractility were also studied in anesthetized dogs. Xanthine alone had no significant effect on the cardiac function and indices of myocardial contractility. However, xanthine oxidase produced a marked decrease in the mean aortic pressure, left ventricular work index, heart rate, cardiac index, left ventricular systolic pressure, left ventricular end-diastolic pressure, (+) and ( ) dp/dt of left ventricular pressure, and other indices of myocardial contractility [(dp/dt)/PAW (pulmonary arterial wedge pressure)]; and an increase in the total systemic and pulmonary vascular resistance. Repeated administration of xanthine oxidase in anesthetized dogs had lesser effects on the cardiovascular system when compared with those from the initial dose of the drug. These results suggest that OFR are cardiac depressant. Clinical situations wherein there is an increased production of OFR or increased formation of xanthine and xanthine oxidase may be associated with decreased cardiac function and contractility. Scavengers of OFR may protect the heart from the deleterious effects of OFR in such clinical conditions. PMID- 8457077 TI - Interaction in cardiovascular crossover studies: the standard and the clinical analysis. AB - The crossover trial, which is considered the most powerful means of determining the efficacy of cardiovascular drugs, is frequently biased by treatment-by-period interactions. A second problem is that the standard analysis (Hills-Armitage analysis) for these biases is unreliable because of a low sensitivity. The author recently introduced an alternative method for the detection of interaction bias entitled the clinical analysis, because it looks at the clinical performance of the separate treatment groups in a trial and not, as in the standard analysis, at the means of the groups. In a mathematical model this analysis was capable of detecting interaction at a 30% lower level than the standard analysis. The present study was undertaken to show not only that the clinical analysis performs better than the standard but also that it enables the investigator to differentiate among different types of interactions, eg, physical carryover effect, rebound phenomenon, and psychological carryover effect. PMID- 8457078 TI - Observations on plasma ANP levels during short-term transient myocardial ischemia produced by PTCA in patients with LAD stenosis. AB - Ten patients with coronary artery disease and stable angina (mean age fifty seven) were included in the study. Five of the patients had normal left ventricular function, 5 had local hypokinesia or akinesia; 8 had one-stem and 2 had two-stem disease, but all had left anterior descending (LAD) lesions ranging from 75% to 100%. Ejection fraction varied between 35% and 75% (mean 59%). Immunoreactive atrial natriuretic polypeptide (ANP) levels in the femoral vein (FV) and the coronary sinus (CS) were measured before, immediately after, and up to twenty-four hours after percutaneous transluminal coronary angioplasty (PTCA) of the LAD. ANP secretion increased by 83% (FV) and 11% (CS) within minutes after PTCA and reached control levels after thirty to sixty minutes. In patients with hypokinesia of the anterior wall, ANP secretion was significantly lower, 48% (FV) and 11% (CS) respectively. ANP secretion during PTCA was higher in patients with concomitant increase in pulmonary capillary pressure (PCP) but was also observed without an increase of PCP, suggesting ventricular ANP secretion. IN conclusion, transient myocardial ischemia leads to immediate ANP secretion even in the absence of significant pressure elevation in the left atrium. As a part of the continuous medical education program of the American College of Angiology the second part of the paper reviews the mechanisms that allow the ischemic heart to counteract the ischemic condition and thus to escape from myocardial infarction. A review of this subject is presently not available in the literature. PMID- 8457079 TI - In vitro pulmonary vasorelaxant effect of the phosphodiesterase inhibitor enoximone. AB - Enoximone is a phosphodiesterase inhibitor that has both positive inotropic and systemic vasorelaxant activities. The latter are mediated by an increase in vascular smooth muscle concentration of cyclic 3'5' guanosine monophosphate. However, the effect of enoximone on pulmonary vasoreactivity is not established. The authors, therefore, have studied its effect on endothelium-dependent relaxation mediated by the endothelium-derived relaxing factor nitric oxide (NO), as well as endothelium-independent relaxation of isolated porcine pulmonary arteries. Enoximone (10(-7) to 10(-4) M) caused a dose-dependent relaxation in all pulmonary arterial rings. This relaxation neither required the presence of the endothelium nor was affected by the addition of the inhibitor of NO synthase omega-nitro-L-arginine methyl ester (10(-4) M). Also, the vasorelaxant response of the rings to the endothelium-dependent vasodilator adenosine diphosphate (10( 10) to 10(-5) M) was not affected by pretreatment with enoximone. The authors conclude that enoximone is a potent vasodilator that relaxes pulmonary vascular rings through mechanisms independent of the endothelium. This endothelium independent vasodilatory effect of enoximone makes it a potentially valuable drug for the treatment of pulmonary hypertension. This particularly applies to diseases in man where NO production by the endothelial cells is impaired. PMID- 8457080 TI - Therapeutic embolization of bronchial artery: a successful treatment in 209 cases of relapse hemoptysis. AB - Still today bronchial artery embolization (BAE) is an important procedure in the management of hemoptysis, as an alternative to, or in association with, surgical or medical therapy. From 1974 to 1990, BAE was performed in 209 patients who suffered from hemoptysis with different etiopathogeneses and severity. Bronchiectasis were the most frequent indication (46%) followed by tuberculosis (31%), cystic fibrosis (16%), lung cancer (4%), and aspergillosis (3%). BAEs were performed by means of polyvinyl alcohol particles and absorbable gelatin sponge. In a few cases complete occlusion of the main truncus of particularly large bronchial arteries was obtained by use of Gianturco steel coin (5 mm o) technique. In the last seven years, together with the traditional angiographic techniques, selective digital angiography (SDA) was performed, above all in preliminary control phases, to evaluate occlusion during embolization. SDA reduced catheterization time and the mean quantity of contrast administered, decreasing side effects; 98% of hemoptysis was controlled in the first twenty four hours, the other 2% in the following forty eight hours; 16% relapses occurred within the first year; 27 patients needed reembolization (15 patients twice, 11 patients three times, 1 patient five times). No complications were seen. If diagnosis, therapeutic indications, operative technique, and equipment selection are adequate, BAE has a high reliability in patients affected by relapsing hemoptysis, which is difficult to resolve. PMID- 8457081 TI - Blood viscosity during long-term treatment with ticlopidine in patients with intermittent claudication. A double-blind study. AB - The aim was to test within a randomized, double-blind trial whether the antiaggregant drug ticlopidine might reduce blood viscosity as has been claimed. Sixteen patients with intermittent claudication were studied before and after three years of treatment with ticlopidine, 500 mg/day, or placebo. At baseline, the viscosity values were significantly higher as compared with a reference group of healthy subjects. Whole-blood viscosity, measured at four different shear rates at hematocrit adjusted to a standard 40%, decreased significantly at follow up, with no difference between ticlopidine treatment and placebo. Hematocrit showed a slight increase in the placebo group. The viscosity parameters were unrelated to lower limb blood flow variables, ankle/brachial index, and walking distances. The mechanism behind the overall decrease in whole-blood viscosity is obscure but could possibly be explained by lifestyle changes. Smoking habits were, however, unaltered. Since plasma viscosity remained increased, it might indicate that some erythrocyte factor, notably red cell aggregability and deformability, had improved. It is concluded that ticlopidine had no long-term effect on blood viscosity. PMID- 8457082 TI - Three-month therapy with calcium-heparin in comparison with ticlopidine in patients with peripheral arterial occlusive disease at Leriche-Fontaine IIb class. AB - Forty patients with a mean age of 62.6 +/- 6 years, 36 men and 4 women, with peripheral arterial occlusive disease (PAOD) at Leriche-Fontaine IIb class, were randomly allocated to one of two treatment groups, receiving either 12,500 IU/day of subcutaneous (sc) calcium-heparin (CAE) or 250 mg/day of oral ticlopidine, each given for ninety days. The following parameters were evaluated before the start of the active treatment period and after thirty and ninety days of treatment: pain-free walking distance (PWD), maximum walking distance (WDmax), systolic and diastolic blood pressure (BP), posterior tibial arterial pressure and Winsor index at rest and after exercise (treadmill), transcutaneous oxygen and carbon dioxide pressures at rest (TcPO2 and TcPCO2 respectively), and time to 50% TcPO2 recovery after three-minute ischemia. Both treatments induced an improvement in PWD/WDmax, which, at the end of the study, were increased by 50.7/58.7% and 31.7/36.2%, respectively, for CAE and ticlopidine treatments, respectively. PMID- 8457083 TI - Determination of arterial diameters, length and mass of the plaque, and theoretical volume in the internal carotid artery by quantitative vascular echography. AB - To study the evolution of atherosclerosis, the consensual changes that occur in the arterial wall, lumen, and atheroma must be evaluated. The authors propose a new, noninvasive method of obtaining arterial diameters, length and mass of plaque, and theoretical volume in the internal carotid artery. The study was performed in 37 patients with different degrees of atherosclerosis (from 20% to 50%). All patients underwent echo examination. Long-axis tomographic planes were recorded with the same angle of incidence by placing a goniometer around the neck. Furthermore, the arterial diameters and the plaque length were measured from photorecordings, and theoretical arterial volume (sum of two bitruncated semiellipsoids), residual volume (Simpson's integral rule), and plaque mass (difference between theoretical vascular volume and residual volume) were calculated. Intraobserver and interobserver variability and reproducibility were tested in all the measurements and calculations. Intraobserver/interobserver variability and reproducibility were found to be less than 8% according to all measurements and calculations. These results indicate that the method is reproducible and allows noninvasive, quantitative assessments of vascular geometry in evolving atherosclerosis. PMID- 8457084 TI - Measurement of cardiac chamber volumes by cine magnetic resonance imaging. AB - Cardiac chamber volumes (both atria and ventricles) in 19 healthy volunteers were measured noninvasively by cine magnetic resonance imaging (MRI). First, cardiac localization was determined from the coronal image by 0.5-T superconducting magnetic imager. Then, transaxial ECG gated multislice spin echo images were obtained from the bottom to the top of the heart. In the last step, cine MRI was performed at each level of all these transaxial spin echo MR images involving the heart. Each cardiac chamber volume at the same phase was calculated by adding chamber areas in each anatomic section multiplied by slice thickness. Left ventricular (LV) end-diastolic volume (EDV) 132.0 +/- 26.9 mL) and LV end systolic volume (ESV) (47.8 +/- 13.9 mL) were smaller than right ventricular (RV) EDV (141.1 +/- 24.8 mL) and RVESV (57.0 +/- 12.6 mL), respectively (p < 0.01). LV stroke volume (84.3 +/- 17.9 mL) was equivalent to RV stroke volume (84.2 +/- 17.6 mL) (r = 0.91, p < 0.01). Left atrial (LA) and right atrial (RA) maximal volumes were 75.8 +/- 15.4 mL and 84.4 +/- 18.7 mL, respectively. LA minimal volume (37.5 +/- 10.7 mL) was smaller than RA minimal volume (47.8 +/- 12.2 mL). These values measured by cine MRI are satisfactory and cine MRI will be a useful method of determining cardiac chamber volumes, especially atrial volumes. PMID- 8457085 TI - Prevention of recurrent deep venous thrombosis with indobufen. A 3-year follow-up study using color duplex scanning. AB - After an episode of deep venous thrombosis (DVT) 123 patients were randomized into two groups: one was prophylactically treated with indobufen (60 patients), an oral antiplatelet agent, and one had no treatment (63) and acted as a control group. They were followed up for three years and scanned with color duplex scanning (CDS) every three months and any time that signs and symptoms suggested a new episode. In patients receiving indobufen the incidence of thrombosis was 5% in three years while it was significantly higher (46%) in the control group. Also 62% of the new episodes in the control group were asymptomatic (33.3% in the treated group). Results suggest that recurrent DVT is common, often asymptomatic, and confused with sequelae of the initial episode. The prophylaxis with indobufen is an effective measure in preventing recurrent thrombosis and avoiding the progressive deterioration of the deep venous system observed after deep venous thrombosis. PMID- 8457086 TI - Serum tumor necrosis factor levels in acute myocardial infarction and unstable angina pectoris. AB - Tumor necrosis factor (TNF) enhances leukocyte adherence to vascular endothelium and increases procoagulant activity in the endothelial cells. Thus it may be implicated in the pathogenesis of acute vascular occlusions. To study the role of TNF in the early stages of acute myocardial infarction (MI), the authors measured circulating TNF levels in the sera of patients with acute MI and unstable angina pectoris. Blood samples were obtained within six hours after onset of chest pain and stored at -70 degrees until tested. A sensitive sandwich enzyme-linked immunosorbent assay (ELISA) test was used for TNF measurement. C-reactive protein (CRP) levels were determined semiquantitatively. Immediate complications such as heart failure, arrhythmia, and shock were also noted. Twenty-four patients with electrocardiographically and biochemically confirmed acute MI and 14 patients with unstable angina pectoris were included in the study. TNF levels were serially assessed at the time of admission and at hours 6, 24, 48, 72, and 96 after onset of chest pain in 2 patients with acute MI. Detectable TNF was found in 13 sera of the acute MI group (range; 10-1510 pg/mL) and 4 sera of the angina pectoris group (range; 15-240 pg/mL). There was no correlation between the serum TNF levels and the occurrence of complications and the extent of myocardial damage. CRP response was unrelated to TNF levels. Contrary to previous reports, serial measurement of TNF revealed that peak values were reached within six hours and disappeared after twenty-four hours.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457087 TI - Echocardiographic features of embolized inferior venacaval filter to the right ventricle--a case report. AB - The authors describe two-dimensional echocardiographic features of an inferior venacaval filter that migrated to the right ventricle. As far as they can determine, this is the first description of the echocardiographic aspects of this clinical entity. PMID- 8457088 TI - Prospective validation of a new model for evaluating emergency medical services systems by in-field observation of specific time intervals in prehospital care. AB - STUDY OBJECTIVE: To develop and validate a new time interval model for evaluating operational and patient care issues in emergency medical service (EMS) systems. DESIGN/SETTING/TYPE OF PARTICIPANT: Prospective analysis of 300 EMS responses among 20 advanced life support agencies throughout an entire state by direct, in field observation. RESULTS: Mean times (minutes) were response, 6.8; patient access, 1.0; initial assessment, 3.3; scene treatment, 4.4; patient removal, 5.5; transport, 11.7; delivery, 3.5; and recovery, 22.9. The largest component of the on-scene interval was patient removal. Scene treatment accounted for only 31.0% of the on-scene interval, whereas accessing and removing patients took nearly half of the on-scene interval (45.8%). Operational problems (eg, communications, equipment, uncooperative patient) increased patient removal (6.4 versus 4.5; P = .004), recovery (25.4 versus 20.2; P = .03), and out-of-service (43.0 versus 30.1; P = .007) intervals. Rural agencies had longer response (9.9 versus 6.4; P = .014), transport (21.9 versus 10.3; P < .0005), and recovery (29.8 versus 22.1; P = .049) interval than nonrural. The total on-scene interval was longer if an IV line was attempted at the scene (17.2 versus 12.2; P < .0001). This reflected an increase in scene treatment (9.2 versus 2.8; P < .0001), while patient access and patient removal remained unchanged. However, the time spent attempting IV lines at the scene accounted for only a small part of scene treatment (1.3 minutes; 14.1%) and an even smaller portion of the overall on-scene interval (7.6%). Most of the increase in scene treatment was accounted for by other activities than the IV line attempts. CONCLUSION: A new model reported and studied prospectively is useful as an evaluative research tool for EMS systems and is broadly applicable to many settings in a demographically diverse state. This model can provide accurate information to system researchers, medical directors, and administrators for altering and improving EMS systems. PMID- 8457089 TI - The emergent problem of ambulance misuse. AB - STUDY OBJECTIVE: The primary objective was to determine whether rates of ambulance misuse varied systematically by type of health insurance. The secondary objective was to determine whether the level of service provided in the ambulance varied by ambulance company ownership. DESIGN: Survey. SETTING: A 175-bed community hospital in central Connecticut. PARTICIPANTS: One hundred forty-five records were selected randomly for study from the records of the 488 patients presenting to the hospital emergency department within a 45-day period. OUTCOME MEASURES: The urgency of presenting complaint and the use of life support measures within the ambulance were obtained from each ambulance run form. Type of health insurance, clinical data, and disposition were obtained from ED records. Ambulance use was deemed unnecessary if the patient's presenting complaint was nonurgent, the patient was ambulatory, and the patient was not ultimately hospitalized. Advanced life support measures were deemed unnecessary if they were applied to patients with nonurgent complaints. RESULTS: Patients with private insurance made appropriate use of ambulances in 77.8% of cases, patients with Medicare did so in 65.8% of cases, and patients with Medicaid did so in 14.7% of cases. These results were statistically significant at P < .001. Among patients with Medicare, ambulance misuse was more common among nursing home residents. Approximately 20% of the observed misuse was related to alcohol intoxication. Although it did not reach statistical significance, we noted a higher frequency of inappropriate use of advanced life support measures in patients brought to the ED by a private ambulance service than for those brought by a municipal service. CONCLUSION: Ambulance misuse is common in the studied community and may be related to the broader problem of the provision of care to the poor or otherwise underserved. Our results raise several interesting questions for further research. PMID- 8457090 TI - Comparison of motor vehicle damage documentation in emergency medical services run reports compared with photographic documentation. AB - STUDY OBJECTIVE: To determine whether emergency medical services (EMS) run reports adequately document vehicle damage when compared with vehicle photographs by using a traffic accident scoring system. DESIGN: A prospective study consisting of three phases: photographing motor vehicle collisions and collecting their respective EMS run reports, traffic accident damage score development, and comparison of photographs to the run reports by emergency medical technicians using the traffic accident damage score. SETTING: Data were collected in North Carolina and Ohio from motor vehicle crashes to which nine different EMS squads responded during a three-year period. TYPE OF PARTICIPANTS: EMS squads ranged from basic to paramedic levels of training. MEASUREMENTS AND MAIN RESULTS: Three emergency medical technicians were unable to determine the area of vehicle damage in 48% and the severity of damage in 61% of the EMS run reports. In contrast, there were no instances in which all three emergency medical technicians were unable to determine both area and severity of damage from the photographs. CONCLUSION: Most EMS run reports do not document vehicle damage adequately. PMID- 8457091 TI - Job satisfaction of paramedics: the effects of gender and type of agency of employment. AB - STUDY OBJECTIVES: To document specific factors important in paramedic job satisfaction and job performance. DESIGN AND TYPE OF PARTICIPANTS: A cohort analysis sampled 63 male public-agency paramedics and 131 private-agency paramedics (90 male, 41 female). METHODS: Three scales from the Michigan Organizational Assessment Questionnaire measured total job satisfaction. A four item scale assessed attitudes toward paramedic job performance. RESULTS: Fire paramedics reported highest levels of overall satisfaction, followed by male and female private-agency paramedics. Fire paramedics reported higher levels of intrinsic job satisfaction (eg, opportunity to learn new things) than private agency paramedics. Differences in extrinsic job satisfaction (eg, pay, benefits) were even greater between fire paramedics and private-agency paramedics. Fire paramedics reported higher satisfaction than female private-agency paramedics with the social rewards of work (eg, the way they are treated by their coworkers). These findings were not explained by age, race, education level, and years on the job. Analysis of the attitudes toward paramedic job performance scale suggested that male paramedics are more likely to believe that female paramedics are not as capable of performing certain job functions. CONCLUSION: Type of agency and gender affect job satisfaction. Male public-agency paramedics are most satisfied, and female private-agency paramedics are least satisfied with their jobs. PMID- 8457092 TI - Helping the helpers: the development of a critical incident stress management team through university/community cooperation. AB - Prehospital emergency services personnel often are exposed to high levels of occupational stress. Besides chronic stress, they can be involved in critical incidents, which cause a well-recognized set of overwhelming emotional reactions. If these reactions are not addressed promptly, emergency responders and their families can suffer further emotional trauma, and this can impair the ability of responders to care for patients in the field. A critical incident stress management team has been established through cooperation between the Charleston Division of the West Virginia University Health Sciences Center and emergency personnel in Charleston, as well as the rural countries in southern West Virginia. This team provides preincident education and postincident interventions for firefighters, police, emergency medical services, and on occasion, hospital emergency department personnel. This team can serve as a model for other such teams to organize to deal with this growing problem in the health care delivery field. PMID- 8457093 TI - A comparison of chest compressions between mechanical and manual CPR by monitoring end-tidal PCO2 during human cardiac arrest. AB - STUDY OBJECTIVE: To compare the use of mechanical and manual chest compressions during cardiac arrest based on continuous monitoring of end-tidal PCO2 (PETCO2). DESIGN: Prospective, randomized, crossover design. SETTING AND PARTICIPANTS: Fifteen consecutive adults ranging in age from 33 to 78 years who presented in nontraumatic cardiac arrest to the emergency department of a large teaching hospital. INTERVENTIONS: Study protocols were begun late in the resuscitation after initial resuscitation attempts were unsuccessful. Patients received four alternating five-minute trials (two manual and two mechanical), being randomized to begin with either technique. Mechanical compressions were performed by a mechanical device at a compression depth of 2 in. Both mechanical and manual compressions were delivered at a rate of 80 with a ventilation delivered after every fifth compression. Persons performing manual CPR were experienced American Heart Association basic life support providers, and no person performed manual CPR more than once during the study period. No resuscitative drugs were administered during the study period. PETCO2 was monitored continuously; those performing manual CPR were blinded to the PETCO2 monitor. Data were analyzed with repeated-measures analysis of variance and Scheffe multiple comparisons with the alpha error rate set of .05. MEASUREMENTS AND RESULTS: Mean PETCO2 during mechanical CPR was 13.6 +/- 4.14 mm Hg compared with 6.9 +/- 2.42 mm Hg during manually performed CPR (P < .001), a difference of 97%. Average mechanical CPR PETCO2 was higher in all cases. No patient was resuscitated successfully. Capnography also indicated that most CPR providers were inconsistent in their chest compressions. CONCLUSION: This study suggests that cardiac output produced with mechanical chest compressions is greater than that produced with manual compressions as demonstrated by the significantly higher PETCO2 levels during mechanical CPR. Reasons for this are unclear. In addition, monitoring of PETCO2 may help optimize chest compressions during CPR. PMID- 8457094 TI - Continuous pulse oximetry during emergency endotracheal intubation. AB - STUDY OBJECTIVE: To determine whether continuous pulse oximetry improves the recognition and management of hypoxemia during emergency endotracheal intubation. DESIGN: A prospective, serial 14-month study. SETTING: Emergency department, Level I trauma center. TYPE OF PARTICIPANTS: All adult patients requiring emergency intubation for whom data collection would not compromise patient care. INTERVENTIONS: All samples were obtained from a finger site at a five-second sampling interval and stored in computer memory. Patients were intubated by the nasotracheal or orotracheal route. MEASUREMENTS AND MAIN RESULTS: One hundred ninety-one consecutive adult patients qualified for the study and 211 intubation attempts were analyzed. Hypoxemia (O2 saturation, less than 90%) occurred during an intubation attempt in 30 of 111 nonmonitored versus 15 of 100 monitored attempts (P < .05), and the duration of severe hypoxemia (O2 saturation, less than 85%) was significantly greater for nonmonitored attempts (P < .05). CONCLUSION: Continuous pulse oximetry monitoring reduces the frequency and duration of hypoxemia associated with emergency intubation attempts. PMID- 8457095 TI - Evaluation of high-yield criteria for chest radiography in acute exacerbation of chronic obstructive pulmonary disease. AB - STUDY OBJECTIVES: The objectives of this study were to assess the incidence of abnormal chest radiographs and to test the validity of previously developed high yield criteria. There is disagreement about the need for chest radiography in acute exacerbation of chronic obstructive pulmonary disease, although high-yield criteria have been developed. DESIGN: Retrospective chart review study. SETTING: County-owned, university-affiliated, urban emergency department. PARTICIPANTS: ED patients seen between January 1988 and July 1991 with chronic obstructive pulmonary disease. RESULTS: Eight hundred forty-seven ED visits were identified; medical records were available for 742. Radiographs were not taken in 8%, leaving 685 ED visits in the study. One hundred nine patients (16%) had significant abnormalities, including 88 new infiltrates, two new lung masses, one pneumothorax, and 20 episodes of pulmonary edema. A history of congestive heart failure and fever was associated with abnormalities, as were findings of rales, pedal edema, and jugular venous distension. There was no association with WBC count, temperature, coronary artery disease, chest pain, or sputum production. Previously published high-yield criteria had a sensitivity of .76; specificity, .41; positive predictive value, 20; negative predictive value, .90; and accuracy, .47. CONCLUSION: Radiographic abnormalities are common findings in acute exacerbation of chronic obstructive pulmonary disease. We found that almost one fourth of radiographic abnormalities are not predictable on the basis of previously developed high-yield criteria. Routine chest radiography should be considered in patients with acute exacerbation of chronic obstructive pulmonary disease to diagnose treatable, radiographically apparent abnormalities. PMID- 8457096 TI - Technique and use of supine oblique views in acute cervical spine trauma. AB - STUDY OBJECTIVE: To determine whether the addition of the supine oblique view of the cervical spine can detect fractures or ligamentous injury not seen on the standard three-view examination. DESIGN: Radiographs of patients with documented cervical spine injury were reviewed retrospectively by three neuroradiologists. Patients were included in the study if the initial interpretation of the three view series was normal and the abnormal supine oblique view enabled a correct diagnosis to be established. SETTING: The emergency department of a university affiliated hospital with Level I trauma center status. TYPE OF PARTICIPANTS: Eighty-three consecutive patients with documented cervical spine injury evaluated during a 20-month period. RESULTS: Eight patients demonstrated abnormality to best advantage on the supine oblique view. These included six fractures and two ligamentous injuries. Five patients had abnormalities confined to the supine oblique view, and the remaining three had subtle abnormalities on the cross-table lateral view. CONCLUSION: The supine oblique view may detect fractures or ligamentous injury not identifiable on the standard three-view examination. We recommend the routine use of a five-view cervical spine series with the inclusion of 30-degree supine oblique views in the evaluation of acute cervical spine injury. PMID- 8457097 TI - The natural history and clinical findings in undifferentiated abdominal pain. AB - STUDY OBJECTIVE: This was a follow-up study of patients diagnosed in and discharged from the emergency department with undifferentiated abdominal pain to establish the natural history of this condition and to define clinical features of patients with undifferentiated abdominal pain. SETTING: ED of a county teaching hospital. DESIGN: Telephone survey of patients at two to three days (first contact) and again at two to three weeks (second contact) after discharge and retrospective chart review. TYPE OF PARTICIPANTS: All patients 18 years or older discharged with the primary diagnosis of undifferentiated abdominal pain from the ED. Excluded were pregnant patients and those presenting with trauma. Patients unavailable for follow-up contact were not included in further data analysis. MEASUREMENTS AND MAIN RESULTS: Four hundred three patients were discharged from the ED with undifferentiated abdominal pain. Of these, 307 (76.1% were available for follow-up information. The female-to-male ratio was almost 3:1. At first contact, 26.8% of all patients were pain-free and another 30% improved. At second contact, 59.1% had no pain, and an additional 28.6% reported improvement. Ten patients were hospitalized during the follow-up period for continued abdominal pain, and no deaths were attributed to abdominal conditions. The largest subgroup of patients with undifferentiated abdominal pain was female patients less than 30 years old. Epigastric pain was the most common patient complaint, with nausea second. The abdomens of most patients were nontender on examination. Abnormal laboratory and radiologic findings in patients with undifferentiated abdominal pain were few. CONCLUSION: Patients with the diagnosis of undifferentiated abdominal pain have a benign short-term course. Almost 88% of patients were pain-free or improved by two to three weeks after their evaluation. No signs or symptoms clearly identified subgroups of patients with undifferentiated abdominal pain. PMID- 8457098 TI - Are baseline prothrombin time/partial thromboplastin time values necessary before instituting anticoagulation? AB - STUDY OBJECTIVES: To determine whether baseline prothrombin time (PT) or partial thromboplastin time (PTT) values provide information that is useful to the clinician before initiating anticoagulation and whether emergency physicians elicit historical information about bleeding disorders before beginning anticoagulant therapy. DESIGN: A three-year retrospective review of the records of 199 patients admitted through the ED with an ICD-9-CM diagnosis of deep-vein thrombosis or pulmonary embolus using a predesigned study sheet that included historical questions, baseline PT and PTT values, treatment given, timing of treatment, and underlying medical problems. SETTING: University-affiliated tertiary-care hospital. MEASUREMENTS AND MAIN RESULTS: Deep-vein thrombosis was the primary diagnosis in 75% of patients. Pertinent historical items were not documented in 92% to 100% of patients. Baseline PT and PTT values were obtained in 94% of patients. An elevated baseline PT was found in 26 patients, all of whom were taking warfarin. An elevated baseline PTT was found in 21 patients. These results were attributed to laboratory error (one), warfarin use (nine), heparin therapy before baseline tests (five), anticardiolipin antibodies (five, one of whom was on warfarin therapy), and unknown causes (three). Heparin therapy was not altered for any patient. CONCLUSION: Emergency physicians rarely document pertinent questions about bleeding disorders before initiating anticoagulation therapy. Baseline PT and PTT values are almost routinely obtained despite the fact that they do not alter therapy or serve as sensitive or specific screening tests. Routine baseline PT and PTT values are rarely needed before initiating anticoagulation. Eliminating such routine testing would result in significant cost savings. PMID- 8457100 TI - Successful conversion of unstable supraventricular tachycardia to sinus rhythm with adenosine. AB - STUDY PURPOSE: To evaluate the efficacy of adenosine in the treatment of emergency department patients with unstable paroxysmal supraventricular tachycardia (PSVT). DESIGN: A retrospective chart review conducted over two years. SETTING: A university-affiliated hospital ED. PARTICIPANTS: Patients with unstable PSVT (systolic blood pressure of less than 90 mm Hg, chest pain, pulmonary edema, and/or altered mental status) who were treated with adenosine. INTERVENTIONS: Patients' preadenosine and postadenosine heart rates, symptoms, and blood pressure were recorded, as were complications and recurrence of PSVT. PSVT was diagnosed by surface ECG. RESULTS: Twelve patients were identified (three men and nine women with a mean age of 47.6 years). Nine patients presented with hypotension (mean systolic blood pressure, 79 mm Hg), ten with chest pain, and six with both chest pain and hypotension. There were no patients with altered mental status or pulmonary edema. Eight patients converted to sinus rhythm with a single 6-mg bolus of adenosine; the remaining four required an additional 12-mg bolus. In all cases, chest pain and hypotension resolved within minutes of conversion to sinus rhythm. There were no clinically significant adverse effects or recurrence of PSVT during ED observation (mean, 1.8 hours). All patients responded to adenosine; none required electrical cardioversion. CONCLUSION: In the unstable patient with PSVT, adenosine appears to be a safe and effective alternative to current advanced cardiac life support-recommended immediate electrical cardioversion. PMID- 8457099 TI - Aortic arch versus central venous epinephrine during CPR. AB - STUDY OBJECTIVE: To determine if delivery of epinephrine to the peripheral arterial system by an aortic arch catheter is more effective than central venous epinephrine administration during cardiac resuscitation. DESIGN: Randomized, nonblinded, controlled trial. TYPE OF PARTICIPANTS: Sixteen mongrel canines (25 to 31 kg). INTERVENTIONS: Animals had aortic arch pressure, and right atrial pressure, superior vena cava infusion, and descending aortic arch infusion catheters placed using fluoroscopy. After ten minutes of ventricular fibrillation, three DC countershocks were delivered over one minute. If unsuccessful, CPR at 120 compressions per minute was begun, and at 60 seconds of CPR, epinephrine (1 mg/50 mL normal saline) was administered either through the superior vena cava or the aortic arch catheter followed by one more minute of CPR. Defibrillation then was attempted and, if unsuccessful, further resuscitative efforts followed advanced cardiac life support guidelines, except route and dose of epinephrine remained the same. MEASUREMENTS AND MAIN RESULTS: Aortic arch pressure, right atrial pressure, and coronary perfusion pressure (diastolic aortic arch pressure minus diastolic right atrial pressure) were recorded continuously. Aortic arch pressure and coronary perfusion pressure increased more rapidly and to a greater magnitude with aortic arch-epinephrine than superior vena cava-epinephrine. Coronary perfusion pressure doubled by ten seconds in seven of eight in the aortic arch-epinephrine group versus none in the superior vena cava-epinephrine group. Aortic arch pressure and coronary perfusion pressure increases consistently plateaued within 60 seconds after aortic arch epinephrine but not after superior vena cava-epinephrine. Return of spontaneous circulation was faster (P < .05) in the aortic arch-epinephrine group. Maximal coronary perfusion pressure after epinephrine correlated with the coronary perfusion pressure immediately before epinephrine administration in both groups, but more strongly in the aortic arch-epinephrine group (P = .0001). CONCLUSION: For an equivalent dose of epinephrine, aortic arch administration produces a more rapid response and more rapid peak effect than central venous administration. The combination of aortic arch-epinephrine administration and aortic pressure monitoring may be useful when initial standard resuscitative measures have not been successful. PMID- 8457101 TI - The use of external, noninvasive pacing for the termination of supraventricular tachycardia in the emergency department setting. AB - STUDY OBJECTIVE: To determine the potential feasibility of external cardiac pacing for the termination of sustained supraventricular tachycardia in the emergency department setting. TYPE OF PARTICIPANTS: Three men and two women (mean age, 34 years) who presented to the ED with a narrow-complex, hemodynamically stable tachycardia that was later proven to be supraventricular in origin. INTERVENTION: Each patient underwent external overdrive pacing using a modified external pacemaker at a pulse amplitude of 120 mA and a rate between 240 and 280 pulses per minute. RESULTS: In four patients, external cardiac pacing was able to successfully terminate the tachycardia without complication. In one patient, the pacemaker was not able to terminate the tachycardia. CONCLUSION: We conclude that external, noninvasive pacing is a feasible means of terminating supraventricular tachycardia in the ED setting. PMID- 8457102 TI - The 'ring sign': is it a reliable indicator for cerebral spinal fluid? AB - STUDY OBJECTIVE: To study the development of a ring sign when blood is mixed with various fluids. METHODS: One drop of blood and one drop of either spinal fluid, saline, tap water, or rhinorrhea fluid were placed simultaneously on filter paper, and the specimens were examined after ten minutes for the development of a ring. A variety of filter paper agents were used, including standard laboratory filter paper, paper towels, coffee filters, and bed linens. RESULTS: All fluids, when mixed with blood, gave rise to a ring sign; blood alone did not. The type of filter paper did not affect the development of a ring. CONCLUSION: In this experimental setting, the ring or halo sign is reliable for detecting cerebrospinal fluids but is not exclusive for cerebrospinal fluid. PMID- 8457103 TI - Effect of fire department first-responder automated defibrillation. AB - STUDY OBJECTIVE: To examine the effect of fire department first-responder defibrillation on time to defibrillation in a mid-sized community with two tiers of emergency medical services (EMS) ambulance response. DESIGN: Retrospective cohort. SETTING: The study area was the region of Hamilton-Wentworth, which has more than 445,000 inhabitants and covers 1,136 km2 (438 square miles). TYPE OF PARTICIPANTS: We studied 297 victims of out-of-hospital cardiac arrest presenting to the EMS system between May 1, 1990, and April 30, 1991. MEASUREMENTS AND MAIN RESULTS: The mean defibrillation interval was decreased from 11.96 minutes to 8.50 minutes (P < .001) by the introduction of fire first-responder defibrillation. Survival was significantly greater with bystander-witnessed arrest, initial rhythm of ventricular fibrillation, and presence of a pulse on arrival in the emergency department. CONCLUSION: In our EMS system, fire first responders were able to provide defibrillation in significantly shorter times than ambulance attendants. Other EMS systems should review their response times and consider instituting first-responder defibrillation as one means of reducing defibrillation intervals. PMID- 8457104 TI - Trauma oblique cervical spine radiographs. PMID- 8457105 TI - EMS systems: opening the 'black box'. PMID- 8457106 TI - Five looks at the Swedish medical care system. PMID- 8457107 TI - Guidelines for implementation of early defibrillation/automated external defibrillator programs. American College of Emergency Physicians. PMID- 8457108 TI - Guidelines for medical direction of prehospital EMS. American College of Emergency Physicians. PMID- 8457109 TI - Severe right ventricular contusion mimicking cardiac tamponade: the value of transesophageal echocardiography in blunt chest trauma. AB - Clinically, severe right ventricular contusion may mimic cardiac tamponade. We report two cases of suspected cardiac tamponade after blunt chest trauma in which the diagnosis of severe right ventricular contusion was made only by transesophageal echocardiography, avoiding unnecessary and hazardous pericardiocentesis. These cases illustrate the value of transesophageal echocardiography in diagnosing blunt chest trauma. PMID- 8457110 TI - Upper-extremity deep-vein thrombosis: thrombolytic therapy with anistrepalase. AB - A patient with primary axillary vein thrombosis was treated successfully in the emergency department with a single IV bolus of anistrepalase followed by continuous IV heparin. The patient's symptoms resolved quickly, and a repeat venogram 16 hours later showed near-complete resolution of the venous obstruction. We discuss briefly the role of thrombolytic therapy in the treatment of upper-extremity deep-vein thrombosis and the potential advantages of using anistrepalase. PMID- 8457111 TI - Successful resuscitation from cardiac arrest using sublingual injection for medication delivery. AB - A 7-month-old child suffered a cardiopulmonary arrest. After eight minutes of basic CPR by the parents, paramedics arrived and found the child in asystole. Endotracheal intubation and peripheral venous access were unsuccessful, and intraosseous equipment was unavailable in the field. The patient then received 1.5 mg epinephrine and 0.15 mg atropine injected sublingually with prompt return of a sinus rhythm and a palpable pulse. One hour after arrival in the emergency department, the patient again arrested, this time fatally. This case may represent the first report of successful resuscitation from cardiac arrest using sublingually injected medications. PMID- 8457112 TI - Magnesium in acute myocardial infarction. PMID- 8457113 TI - Grand mal seizures & cocaine use. PMID- 8457114 TI - Postarrest hypertension in pediatric patients. PMID- 8457115 TI - Cerebral resuscitation. PMID- 8457116 TI - Management of airway obstruction in patients with congenital heart defects. AB - Airway obstruction may complicate the course of infants undergoing repair of congenital heart disease. Airway obstruction was encountered in seven patients following surgery for complex congenital heart defects (two with interrupted aortic arch, one with pulmonary atresia and a ventricular septal defect, one with tetralogy of Fallot and an abnormal left anterior descending coronary artery, one with truncus arteriosus, and two with complex univentricular heart). In four patients, a conduit was implanted at the time of surgery. In all cases, bronchoscopy accurately demonstrated the cause of the airway obstruction. Two infants had hypoplasia of the left bronchus, and five had tracheobronchomalacia associated with extrinsic compression of the airway by a great vessel or conduit. All were treated conservatively with therapeutic bronchoscopy, tracheotomy, and/or stenting with prolonged mechanical ventilation. Follow-up ranged from 2 to 40 months. Four infants have been weaned from mechanical ventilation and decannulated; two are awaiting decannulation; and one was decannulated and died awaiting surgical repair. To reduce morbidity in infants undergoing surgery for congenital heart disease, the presence of preoperative airway anomalies should be sought and surgery planned to avoid airway compression. Conservative management using diagnostic and therapeutic bronchoscopy, tracheotomy, and stenting together with prolonged ventilator care is rewarding. PMID- 8457117 TI - Thyroarytenoid intramuscular pressures. AB - The aim of this research has been to investigate the measurement of laryngeal intramuscular fluid pressures as a technique for assessment of laryngeal muscle activity for diagnostic or experimental purposes. Simultaneous measurements of contractile force, intramuscular fluid pressure, and electromyographic signals were made under isometric conditions in the vocal fold muscles of anesthetized dogs during supramaximal stimulation of the recurrent laryngeal nerve. Covariation of force and pressure was studied in twitch and tetanic contractions, over a range of stimulation frequencies. Tetanic pressure rises were usually smaller than in human limb muscles, but were of sufficient magnitude that effects on blood flow and muscle metabolism are probable. Analysis of relations between pressure and force records demonstrated that intramuscular pressure variations correlated closely to isometric force in their time course. This finding suggests the potential significance of this measure as a relatively nonintrusive indicator of the level of force of muscles involved in laryngeal function, and as a physiological measure of importance. PMID- 8457118 TI - Laryngotracheal reconstruction for subglottic stenosis. AB - Laryngotracheal reconstruction (LTR) has been employed for the treatment of severe laryngotracheal stenosis for the past 6 years at Johns Hopkins Hospital. Thirty-one children underwent LTR with costal cartilage grafting, 24 of whom had Aboulker stents placed. Short stents were used in 22 patients. Six patients received definitive treatment in a single-stage LTR; 1 child had no stent placed. Twenty-six (84%) of the 31 patients were decannulated. It was concluded that decannulation can be obtained in selected patients with the short Aboulker stent or single-stage LTR. A new classification system for laryngotracheal stenosis, based on objective measurements and the separate analysis of posterior glottic fibrosis, was developed. The proposed classification system allows recommendations for treatment. Moreover, it can be easily reproduced and may facilitate comparison of results. PMID- 8457119 TI - Vocal cord paralysis caused by esophageal cancer surgery. AB - Esophageal cancer surgery was the cause of paralysis in 111 (16.7%) of 664 patients with vocal cord paralysis seen from 1981 to 1990 at Kurume University Hospital. Eighty-six patients had unilateral paralysis, whereas 25 had bilateral lesions. Of the 111, 95 (86%) had hoarseness and 59 (53%) had aspiration. The crude survival rate was 63% for 1-year, 32% for 3-year, and 22% for 5-year follow up. The average life expectancy was short. The general condition was poor in many patients. Thirty-four of the 136 paralytic vocal cords (25%) recovered mobility. An intracordal silicone injection was done in 30 patients, and a medialization procedure was performed in 1. The vocal function was improved in the majority of cases. In 4 patients, severe aspiration persisted following intracordal injection. Of the 4, 1 had cricopharyngeal myotomy and laryngeal suspension and 2 underwent total laryngectomy. The fourth patient died of aspiration pneumonia. The results of the review of the 111 patients have led us to the following treatment policy for patients with vocal cord paralysis caused by esophageal cancer surgery. When the patient has aspiration, vocal cord medialization should be performed as early as possible. If severe aspiration persists even after the medialization procedure, some additional intervention, including cricopharyngeal myotomy, laryngeal suspension, laryngotracheal separation, or total laryngectomy, should be considered. When hoarseness is the only major problem, the prognosis of vocal cord paralysis should be determined on the basis of the state of the recurrent laryngeal nerve and, if available, electromyography findings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457120 TI - Congenital oral synechiae. AB - Major congenital synechiae of the oral cavity constitute a clinically confusing spectrum of abnormalities. On the basis of clinical data, we propose two categories: 1) abnormalities secondary to persistence of the buccopharyngeal membrane and 2) abnormalities secondary to formation of ectopic membranes. An ectopic membrane results from abnormal fusion and can be subclassified as a subglossopalatal membrane, glossopalatal ankylosis, or syngnathia. This classification is supported by embryologic studies and is used to reclassify all cases reported since 1900. Distinct differences, such as the presence of associated limb anomalies, emerge; these are reviewed and add support to the proposed classification. PMID- 8457121 TI - Vestibular and balance rehabilitation therapy. AB - A prospective observational study of the performance of patients enrolled in an individually customized program of habituation and balance rehabilitation physical therapy was conducted from January 1988 to January 1990. Patients ranged in age from 20 to 89 years, with a wide variety of diagnoses. Two global outcome measures--posttherapy symptom response score and pretherapy and posttherapy disability score--were developed and used to judge overall patient performance. In addition, two specific indicators--one for balance performance (dynamic posturography) and one for sensitivity to rapid head movements (motion sensitivity quotient)--were used to measure performance in these two areas. Results indicate statistically significant changes before versus after therapy for both specific measures, and 80% to 85% of the patients showed a reduction in symptoms and disability score following therapy. Analysis of variance and multiple regression analysis indicate that nature of symptoms, pretherapy disability level, history of head injury, and results on dynamic posturography were the variables most predictive of therapy outcome, while age and duration of symptoms made no difference. Other variables, such as medications and site of lesion, were found to affect the length of therapy but not the outcome. PMID- 8457122 TI - Cutaneous squamous cell carcinoma occurring in a pectoralis major myocutaneous flap. Case report and literature review. AB - The pectoralis major myocutaneous flap is a reliable regional flap commonly used for the reconstruction of head and neck defects. We report a case of a squamous cell carcinoma that occurred on the cutaneous paddle of a pectoralis flap in a patient with previous chest wall lesions. The need for a careful history of previous chest wall cutaneous lesions is stressed in patients who are to undergo this type of reconstruction. PMID- 8457123 TI - Erythromycin in acute laryngitis in adults. AB - Moraxella catarrhalis and Hemophilus influenzae are isolated from the nasopharynx in 50% to 55% and 8% to 15%, respectively, of cases of acute laryngitis in adults. This finding indicates that these organisms, M catarrhalis in particular, are in some way involved in the pathogenesis of the disorder. In the present double-blind, placebo-controlled trial, the effect of erythromycin ethylsuccinate (0.5 g twice a day for 5 days) on the elimination of nasopharyngeal pathogens and reduction of clinical signs of upper respiratory tract infection, as well as on subjective complaints, was evaluated in 106 adults with acute laryngitis. The bacterial isolation rates at presentation were M catarrhalis 50%, H influenzae 18%, and Streptococcus pneumoniae 4%. In the 99 patients who completed the study, the elimination of M catarrhalis after 1 week was better in the erythromycin group (25 of 30 cases) than in the placebo group (6 of 19 cases; p < or = .00038). The elimination of H influenzae was unaffected by erythromycin. Otolaryngologic examination did not reveal any significant group differences regarding laryngitis, pharyngitis, or rhinitis. Voice quality was improved after 1 week, irrespective of treatment. However, as compared to the placebo group, the erythromycin group reported fewer voice complaints after 1 week and fewer coughing complaints after 2 weeks. As acute laryngitis in adults is self limiting, and subjective symptoms are spontaneously reduced after 1 week in most cases, antibiotic treatment does not seem warranted as a general policy. However, erythromycin may be justified in patients who are professionally dependent on voice function. PMID- 8457124 TI - Efficacy of ceftibuten for acute otitis media caused by Hemophilus influenzae: an animal study. AB - Ceftibuten is a new oral cephalosporin with an unusual stability to beta lactamases that can hydrolyze other extended-spectrum cephalosporins. Using the chinchilla animal model, we compared the efficacy of ceftibuten (n = 33) with that of saline (n = 34), ampicillin (n = 32), and cefixime (n = 31) for the treatment of acute otitis media caused by beta-lactamase-producing nontypeable Hemophilus influenzae. Ceftibuten was superior to ampicillin regarding the time necessary to sterilize the middle ear (p < .001) and eliminate effusion (p < .001). The mean days of therapy required for bacteriologic cure were 2.57 for ceftibuten, 2.95 for cefixime, 7.95 for ampicillin, and 8.16 for saline. At the conclusion of therapy, chinchillas treated with ceftibuten had a significantly lower prevalence of positive cultures and middle ear effusion than did animals treated with ampicillin. No significant differences were observed between ceftibuten and cefixime. The results of this randomized, investigator-blinded experiment warrant further consideration of ceftibuten as a second-line agent for acute otitis media caused by ampicillin-resistant H influenzae. PMID- 8457125 TI - Round window membrane in serous and purulent otitis media. Structural study in the rat. AB - The rat was used as an animal model to reveal structural alterations in the round window membrane (RWM) during serous otitis media (SOM) and purulent otitis media (POM) over a 6-week period. Comparison of POM animals and control animals showed that the RWM in the former became almost six times as thick as that in controls, whereas that of SOM animals was twice as thick. The structural changes in the RWM in POM animals were confined mainly to the epithelium facing the middle ear cavity and the subepithelial space, which was invaded by inflammatory cells and exhibited dilated vessels. The normal flat epithelium was transformed via cuboidal cells to a cylindric epithelium containing both ciliated and goblet cells. In SOM animals, light microscopy revealed only minor changes in the RWM structure. Ultrastructurally, however, the connective tissue layer exhibited dense aggregations of collagen, increased numbers of fibroblasts, and, in one case, elastic fibers. This last phenomenon was not observed in either POM ears or normal ears. The study showed that various inflammatory conditions of the middle ear, both noninfectious (SOM) and infectious (POM), can cause different structural alterations of the RWM. These structural changes may influence passage through the RWM differently. PMID- 8457126 TI - Computed tomographic diagnosis of radiation-induced internal carotid artery thrombosis. PMID- 8457127 TI - Hyalinizing trabecular adenoma of the thyroid gland. AB - Hyalinizing trabecular adenoma is a follicular-derived tumor of the thyroid gland with a strong predilection for women. In the reported cases, the biologic course has been benign and without recurrences. The most important histologic differential diagnosis is medullary carcinoma, particularly the encapsulated form of the neoplasm. PMID- 8457128 TI - Three-dimensional analysis of murine laryngeal development. AB - This study defines the critical stages in the prenatal development of the mouse larynx. Three-dimensional computer-generated solid model reconstructions display the changing anatomic relationships during laryngeal development from the earliest respiratory primordium to the mature laryngeal vestibule. These reconstructions demonstrate that the laryngeal vestibule forms as a result of a cephalocaudal separation of the epithelial lamina, thereby establishing communication between the laryngeal cecum and the pharyngoglottic duct. These results support the hypothesis that the cause of congenital supraglottic and glottic malformations is an incomplete separation of this epithelial lamina. The infraglottic lumen remains patent during laryngeal development. Continued lengthening of the foregut between the infraglottis and the carina forms the trachea. This is contrary to the 19th-century concept of an ascending tracheoesophageal septum. Formation of the laryngeal cartilages, muscles, and innervation is portrayed by the reconstructions; with minor variations, they correlate closely with earlier wax reconstructions of human laryngeal development. Future research with this animal model can provide additional insights into the complex mechanisms involved in congenital malformations of the larynx. PMID- 8457129 TI - [Renal involvement in autoimmune enteropathies]. AB - The authors report on a infant who presented with an auto-immune enteropathy characterized by the association of a protracted diarrhea, a neonatal insulin dependent diabetes, and a dermatitis and who developed a nephrotic syndrome at 4 months of age. A renal biopsy showed a membranous glomerulonephritis (MGN) with IgG linear deposits along the tubular basement membranes (TMB). By indirect immunofluorescence anti-enterocyte antibodies together with anti-TMB antibodies and anti-renal brush border (BB) antibodies were found in the serum of the patient. The patient received various immunosuppressive drugs that failed to improve the disease. In the course of the disease the anti-TBM antibodies disappeared progressively but the BB antibodies persisted. A review of the literature indicates that renal involvement is not uncommon in auto-immune enteropathy and in 5 cases it has been reported as being characterized by a nephrotic syndrome related to the presence of a MGN. In 4 of these cases MGN was associated with the presence of anti-TBM antibodies and in the remaining one with anti-BB antibodies. This case report shows that in human pathology, auto antibodies to BB proteins may, as well as in experimental models, be responsible for the development of a MGN. It suggests a close relationship (probably a common epitope) between the renal BB proteins and the proteins of the gut epithelium. PMID- 8457130 TI - [Renal transplantation in children under five years of age. Experience at the Hopital des Enfants-Malades]. AB - From 1976 through 1991, 50 renal transplants (with 7 kidneys from living related donors and 43 cadaver kidneys) were performed in 47 children under five years of age (range 11 to 59 months) at the Enfants-Malades Hospital, Paris, France. Donor age ranged from 3 months to 53 years. Six of the seven kidneys from living related donors are currently functioning after a follow-up of 6 months to 8 years, whereas actuarial survival of cadaver kidneys was 70% at one year and 66% at five years. The main cause of graft loss was vascular thrombosis (40% of lost kidneys). In the most recent years of the study period, graft survival was substantially improved by routine prophylactic anticoagulant therapy with low molecular weight heparin: one-year graft survival rate was 83% in the 23 children grafted between 1989 and 1991. Posttransplantation growth was closely related to quality of graft function: among the 29 children with sufficiently long follow-up the 19 patients with normal renal function exhibited normal or catch-up growth, whereas the ten patients with chronic renal failure or recent rejection had poor growth. Complications were uncommon with the exception of hypertension. Mortality rate was 12%, i.e., only slightly higher than in older pediatric kidney recipients. Achievement at school was normal in most cases (with a lag in only five patients). Provided effective therapy is given to prevent the main adverse outcome (i.e., vascular thrombosis), renal transplantation does not involve excessive risks even in infants as young as one year of age. PMID- 8457131 TI - [Sugar diabetes after renal transplantation in children]. AB - Posttransplant diabetes mellitus is ascribed to the use of corticosteroids. Because use of cyclosporine has been associated with increased rates of posttransplant diabetes mellitus, risk factors for this condition have been studied in adults and found to include older age, excessive body weight, and a family history for non-insulin-dependent diabetes mellitus. Only about 1% of children develop diabetes mellitus after transplant surgery. A study of pediatric transplant recipients with diabetes mellitus and of pediatric renal transplant recipients suggested that posttransplant diabetes mellitus may be more common in children with risk factors and may reveal types of diabetes which are infrequent in childhood, e.g., non-insulin-dependent diabetes mellitus which would have gone undiagnosed until adulthood in the absence of corticosteroid therapy. In contrast, corticosteroids apparently had little influence on glucose tolerance in subjects free of risk factors. The effect of corticosteroids seemed to be somewhat less marked than that of renal function impairment. PMID- 8457132 TI - [Evaluation of the efficacy and tolerance of three antihypertensive agents used as single-drug therapy, nifedipine, prazosin and acebutolol in severe, idiopathic hypertension in adolescents]. AB - The antihypertensive efficacy of single-drug therapy with nifedipine (N), prazosin (P), or acebutolol (A) and the influence of these agents on coronary risk factors including hypoglycemia, hyperuricemia, and hyperlipidemia, were studied in adolescents with hypertension. Ninety patients (73 girls and 17 boys) aged 14 to 18 years with idiopathic hypertension (IH) were randomized into three groups. Each group received N, P, or A as single-drug therapy for six months. Systolic and diastolic blood pressures fell in all three groups, from 152/90 mmHg to 127/70 mmHg* with N, from 150/90 mmHg to 121/70 mmHg* with P, and from 148/92 mmHg to 122/74 mmHg* mmHg with A. In 17% of cases, N failed to reduce blood pressures below the 90th centiles. Heart rate was not influenced by N or P but decreased from 84 to 75 bpm with A. Although none of the drugs modified serum uric acid levels, fractional uric acid secretion rose with P and A (from 4.1% to 6% with P; and from 4.4% to 6% with A). The lipid profile remained unchanged under N and P, whereas a decrease in serum LDL-cholesterol from 99.6 to 88.8% mg* was seen with A. Fasting serum glucose levels increased from 86.4 to 92.7 mg %* in the group given A. N, P, and A are suitable for single-drug therapy of IH in adolescents; the most appropriate drug should be selected on the basis of medical history. PMID- 8457133 TI - [Treatment of renal vein thromboses in the newborn]. AB - Surgical thrombectomy is not a rational approach to neonatal renal vein thrombosis since the occlusion mainly involves intrarenal branches rather than the main renal vein, which is even patent in some instances. Conservative management combines supportive therapy for renal failure and systemic hypertension, if needed, and either heparin or thrombolytic agents. Streptokinase has proven difficult to handle in neonates and should not be used. Urokinase has been used in 18 patients but results are difficult to interpret because these cases occurred over an 18-year period. Plasminogen tissue activator, the latest thrombolytic agent developed, has been used in few pediatric patients. An international task force is currently studying whether or not a randomized study is warranted to provide data for standardizing thrombolytic therapy in pediatric renal vein thrombosis. PMID- 8457134 TI - [Contribution of imaging techniques in acute neonatal renal pathology]. AB - Ultrasound is the first imaging modality used to evaluate acute renal disease in neonates. Normal findings and abnormalities seen in venous or arterial thrombosis, hemodynamic shock, or sepsis are reviewed. Transient changes due to intoxications, tubular disorders, or congenital nephrotic syndrome are considerably less common. PMID- 8457135 TI - [Characteristics of the fibrinolytic system in the newborn]. AB - Recent development of microassays and determination of age-specific normal ranges have shed new light on the components and functioning of the neonatal fibrinolytic system. Plasminogen and tissue plasminogen activator levels are low in neonates, who generate plasmin more slowly and in smaller amounts than adults. Quantitative and qualitative changes occur as the fibrinolytic system matures. This is also true of the coagulation system responsible for the production of thrombin, which is the target for plasmin. These data are essential to assess the risk of thrombosis in neonates and, if appropriate, to guide management decisions including selection of a thrombolytic agent, of the optimal dosage, and of the best laboratory tests for monitoring purposes. Ongoing studies are investigating the mechanisms involved in neonatal lysis of thrombin clots occurring naturally or as the result of thrombolytic therapy. PMID- 8457136 TI - [Thrombosis of the renal veins in the newborn: treatment and long term prognosis]. AB - Thirty-nine neonates with renal vein thrombosis diagnosed in our hospital department between 1973 and 1991 were studied retrospectively. Twenty-five patients were and 14 were not treated with urokinase (UK). Among the five deaths (13%), four occurred at the acute stage from non-renal complications and one occurred at the age of three months from end-stage renal failure. Eight patients (21%) have moderate renal failure after a mean follow-up of 7.4 years; a single patient (2%) developed end-stage renal failure after 7.9 years and 25 patients (64%) have a normal glomerular filtration rate after a mean follow-up of 4.5 years. Rates of death and chronic renal failure were 8% and 32%, respectively, in the group given UK and 21% and 7%, respectively, in the group not given UK. Among 54 involved kidneys, only 10 (19%) recovered normal function and morphological features. Functional impairment was seen in 11 of 37 (30%) kidneys treated by UK and 10 of 17 (59%) kidneys not treated by UK. Although these data suggest that UK may be effective in promoting recanalization of renal veins obstructed by thrombosis, confirmatory evidence could be obtained only by performing a prospective therapeutic trial. PMID- 8457137 TI - [Growth and protein metabolism in chronic metabolic acidosis from experimental renal insufficiency]. AB - Two studies of uremia-induced chronic metabolic acidosis (CMA) were carried out to determine: 1) the level of acidosis beyond which growth failure occurs; 2) the protein metabolism anomalies which are associated with growth failure. Rats rendered uremic by subtotal nephrectomy were fed a diet containing sufficient protein amounts (30% casein) to induce CMA. CMA was left uncorrected in half the rats (group A) and was corrected by administration of bicarbonate in the other half (group B). 1) Fifty-two group A rats were compared with 52 group B rats matched for renal function. Results showed that a) CMA failed to reduce food intake; b) weight gain decreased only when CMA was profound (pH < 7.20) whereas reductions in length gain occurred at less severe levels of acidosis (pH < 7.25) suggesting that bone may be more susceptible to CMA than muscle mass. 2) Protein fractional synthesis rate was evaluated in skeletal muscle after a flooding dose of 3H-phenylalanine in group A rats (pH 7.22 +/- 0.01, HCO3-: 15.2 +/- 0.8 mmol/l) and group B rats matched for renal function. Values were identical in both groups (10.4 +/- 0.5 vs 10.8 +/- 0.5%/day). However, fractional muscle protein accretion rate was decreased in group A rats. These data demonstrate that CMA-associated growth failure in uremia is due to increased breakdown of protein with no change in protein production. PMID- 8457138 TI - [Antenatal form of Bartter's syndrome]. AB - Six cases of tubular disorder of antenatal onset responsible for biological manifestations characteristic of Bartter syndrome and severe hypercalciuria are reported. In all six cases, severe hydramnios occurred during pregnancy between the 26th and 28th week after the last menstrual period. All six patients were born prematurely; gestational age ranged from 20 to 35 weeks. Major polyuria with dehydration occurred immediately after birth. The amounts of water and sodium needed to compensate urinary losses ranged from 280 to 370 ml/kg/day and 25 to 43 mmol/kg/d, respectively, during the first two postnatal months. Decreased serum potassium levels and increased plasma levels of renin and aldosterone were seen in all six patients. Increased urinary excretion of calcium was evidenced during the first postnatal week in three cases. Urinary calcium excretion in the six patients ranged from 15 to 30 mg/kg/d. Nephrocalcinosis developed in all six patients and two patients developed urinary lithiasis. One patient died at one month of age from necrotizing enteropathy. The five remaining patients gradually developed severe growth failure with measurements between 4 and 5.5 SDs below the mean. These five patients had evidence of hyperparathyroidism including increased serum levels of parathyroid hormone (5/5), increased serum alkaline phosphatase activity (4/5), and roentgenographic bone changes (1/5). Ionized calcium assays performed in three of the five patients disclosed low values (range 1.25-1.47 mmol/l; mean = 1.35; normal values = 1.42-1.62), although total serum calcium levels were normal or high (range 2.16-2.98 mmol/l; mean 2.61; normal values = 2.45-2.65) probably as a result of chronic dehydration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457139 TI - Adverse effect of antipyretic agent on serum zinc. AB - To study the pathogenesis of the zinc deficiency that is sometimes found postoperatively, the serum concentration of zinc was determined in 35 patients before, during, and after thoracoabdominal surgery. Preoperatively, a serum zinc level below 60 micrograms per 100 ml was recorded in four of 16 patients tested and was associated with severe anorexia. Postoperatively, the serum zinc level was significantly reduced for up to four days, when the patient was unable to eat. After the start of oral feeding, the average serum zinc level returned to normal. The serum zinc level decreased rapidly in two patients after bouts of severe sweating produced by an antipyretic agent (diclofenac). In another patient, the serum zinc level decreased rapidly following the loss of a large volume of intestinal fluid via an intestinal stoma. Factors leading to low serum concentrations of zinc thus include anorexia, operations, antipyretic agents, and the loss of intestinal fluid. PMID- 8457140 TI - Embryotoxicity and teratogenicity of Cu2+ and Zn2+ for Xenopus laevis, assayed by the FETAX procedure. AB - Cupric chloride (CuCl2) and zinc chloride (ZnCl2) were tested by the FETAX (Frog Embryo Teratogenesis Assay: Xenopus) procedure in the South African frog, Xenopus laevis. The median teratogenic concentrations (EC50) of Cu2+ and Zn2+ were 2.5 and 40 mumol per L. The median embryolethal concentrations (LC50) of Cu2+ and Zn2+ were 22 and 850 mumol per L. The teratogenic indices (TI = LC50/EC50) were 8.8 for Cu2+ and 21 for Zn2+. Both metal ions were shown to be potent teratogens for Xenopus, causing concentration-related increases of eye, gut, facial, notochord, and cardiac anomalies. PMID- 8457142 TI - Aldose reductase and its inhibition in the control of diabetic complications. AB - Aldose reductase is a rate limiting enzyme in the polyol pathway associated with the conversion of glucose to sorbitol. The enzyme is located in the eye (cornea, retina, lens), kidney, myelin sheath, and also in other tissues less involved in diabetic complications. Experiments in diabetic animals have implicated sorbitol accumulation in the lens to the development of cataracts. The use of inhibitors of aldose reductase in animal studies has demonstrated that diabetic complications such as cataracts, nephropathy, and slowing of nerve conduction can be ameliorated. While an osmotic effect can explain the physical changes in the lens leading to cataract formation, the effect of sorbitol accumulation in other tissues and the resulting diabetic complications has been linked to the depletion of myoinositol content resulting in a derangement of sodium-potassium adenosine triphosphatase activity. Since glucose and other hexoses are poor substrates for aldose reductase, it is only in hyperglycemia when the enzyme hexokinase is saturated that aldose reductase is activated, leading to accumulation of sorbitol. The kinetics of inhibition of aldose reductase by a variety of inhibitors has been delineated. The dose required varies from inhibitor to inhibitor and is consistent with their inhibition constants. Toxicity is a consideration in the use of some of the inhibitors, as was demonstrated with sorbinil which caused hypersensitivity reactions in 10 percent of patients. Other inhibitors such as tolerant have shown efficacy and are under clinical investigation. Interpretation of results obtained with aldose reductase inhibitor therapy in human subjects suggest that these inhibitors are effective at early stages of diabetic complications. PMID- 8457143 TI - Predictive value and informational value of diagnostic test results. AB - If clinical quality assurance and cost-effectiveness of diagnostic testing are to be measured, some sort of measurement of the clinical value of a test result is needed. The predictive value of a test result is not a real measure of its clinical value, and, particularly, when used in the later stages of a diagnostic workup, it can be misleading. Using the same data that go into a calculation of predictive value, the clinical value can be determined according to the amount of useful information that is provided by a test result. Cost-effectiveness can be expressed as dollars per bit of diagnostic information. PMID- 8457141 TI - Mg(2+)-deprivation enhances and Mg(2+)-supplementation diminishes the embryotoxic and teratogenic effects of Ni2+, Co2+, Zn2+, and Cd2+ for frog embryos in the FETAX assay. AB - The influence of Mg2+ on the embryotoxicity and teratogenicity of Ni2+, Co2+, Zn2+, and Cd2+ for Xenopus embryos was studied by an adaptation of the FETAX protocol. In seven assays, 25 groups of embryos were grown from 5 to 101 hours post-fertilization in FETAX media that contained five graded MgCl2 concentrations (0, 6.2, 62, 620, or 6,200 mumol per L), with or without added NiCl2 (56 mumol per L), CoCl2 (1,800 mumol per L), ZnCl2 (300 mumol per L), or CdCl2 (18 mumol per L). In FETAX assays performed with the standard Mg2+ concentration (620 mumol per L), the incidence of malformations in control embryos averaged 5.4 (SD +/- 1.3) percent; the incidence of malformations in the controls was increased at low Mg2+ concentrations (32 +/- 7 percent at 62 mumol per L; 100 percent at greater than or equal to 6.2 mumol per L). The specified additions of Ni2+, Co2+, Zn2+, or Cd2+ caused death in < 10 under standard conditions (620 mumol Mg2+ per L). Mg(2+)-deprivation greatly enhanced and Mg(2+)-supplementation significantly reduced the incidence and severity of the teratogenic and embryotoxic effects of Ni2+, Co2+, Zn2+, and Cd2+ (p < 0.0001 by analysis of variance [ANOVA]). To explain these findings, the authors speculate that Mg2+ competes with the other divalent metal ions for a carrier mechanism involved in metal absorption or cellular uptake, or for binding to critical molecular targets. PMID- 8457144 TI - Tuberculosis and the New York prisons. PMID- 8457145 TI - 6-Dimethylamino-9-(beta-D-arabinofuranosyl)-9H-purine: pharmacokinetics and antiviral activity in simian varicella virus-infected monkeys. AB - 6-Dimethylamino-9-(beta-D-arabinofuranosyl)-9H-purine (ara-DMAP) effectively prevented the development of rash and appreciably reduced viremia in simian varicella virus-infected monkeys. Doses of 100 and 50 mg/kg/day, administered orally, were highly effective. The lowest dose of 20 mg/kg/day was much less effective in preventing moderate viremia. However, the 20 mg/kg/day did prevent the development of rash in two of three monkeys. All three doses of ara-DMAP reduced liver infection as reflected by lower aspartate aminotransferase values in the sera of the African green monkeys. Orally administered ara-DMAP was rapidly absorbed. However, significant variation among individual monkeys in the AUC values, peak plasma levels, and plasma half-lives were observed. PMID- 8457146 TI - The anti-HIV activity of the phytochemical alpha-terthienyl. AB - The plant trithiophene, alpha-terthienyl (alpha T), was evaluated for activity against the human immunodeficiency virus (HIV-1). Antiviral activity specifically required long wavelength light (UVA, 320-400 nm). The compound had little or no activity in visible light or in the dark. The anti-HIV effect was UVA-dose dependent and was proportional to the concentration of alpha T, according to several parameters of virus infectivity and replication. The efficacy was decreased to some extent by the presence of bovine serum in the reactions; but under optimal conditions 0.1 microgram/ml. alpha T (3 x 10(-7) M) could inactivate 10(4)-10(5) infectious particles. In contrast poliovirus and Coxsackievirus infectivity were relatively resistant to alpha T + UVA. PMID- 8457147 TI - Effects of therapy with an immunomodulator (imiquimod, R-837) alone and with acyclovir on genital HSV-2 infection in guinea-pigs when begun after lesion development. AB - We evaluated the effects of the immunomodulator, imiquimod (R-837) applied topically, alone and in combination with i.p. acyclovir (ACV) on acute, recurrent and neural HSV-2 genital infection in guinea-pigs when 10 days of therapy was begun after HSV lesions developed. The combined therapy was most effective, significantly reducing the severity of the acute disease, as early as 2 days (P < 0.05), and vaginal viral shedding (P < 0.05) as early as 1 day after therapy was begun. The total lesion score for the acute disease was also significantly less in the group receiving imiquimod and ACV (5.4 +/- 0.5) compared to controls (13.1 +/- 1.2, P < 0.001) or imiquimod alone (9.8 +/- 1.2, P < 0.05). Therapy, however, had no significant effect on the number of days with recurrent lesions. Imiquimod increased the lymphoproliferative response to HSV (P < 0.01), while combined therapy reduced HSV antibody titers (P < 0.01) on day 28 compared to placebo and also reduced the effect of imiquimod alone on the lymphoproliferative response. The combination of this effective immunomodulator, imiquimod, and acyclovir appears to provide effective therapy for acute genital HSV-2 infection even when begun after lesion development. PMID- 8457148 TI - Alkaloids of Cynanchum vincetoxicum: efficacy against MDA-MB-231 mammary carcinoma cells. AB - Alkaloids 1-4 from Cynanchum vincetoxicum (asclepiadaceae) (Scheme 1) do not have affinity to the oestrogen receptor but they inhibit the growth of the hormone independent mammary carcinoma cells MDA-MB-231 (Fig. 1) and bind to nucleosides and nucleotides (Table 1). Intercalation was not observed. PMID- 8457149 TI - [Cyclic ureas. 1. Racemates and enantiomers of hexahydropyrimidine-2-ones: synthesis, configuration and sedative-hypnotic action]. AB - The racemates and the enantiomers of the hexahydropyrimidin-2-ones 2a-2e which can be regarded as cyclic ureas are obtained from the racemates and the enantiomers of the barbiturates 1a-1e by reduction with LiAlH4/AlCl3. The enantiomers of 2a-2d, dextrorotatory in ethanol, possess S-configuration. In a study with rats all cyclic ureas synthesized showed sedative-hypnotic activity. Some of the enantiomers exhibited marked enantioselecive differences in their potency. PMID- 8457150 TI - Synthesis and platelet aggregation inhibiting activity of acid side-chain modified hydantoin prostaglandin analogues. AB - A series of hydantoin prostaglandin analogues, in which the hexamethylene moiety of the acid side chain was replaced by other spacing groups possessing either ether, sulphide and/or olefin functionality, were prepared and evaluated for platelet aggregation inhibiting activity. The 4-thia analogue 13*) proved to be the most potent inhibitor (ca. 22x PGE1) and the 3-thia- and 3-oxa-analogues, 6 and 10 respectively, are approximately equipotent with BW245C (ca. 14x PGE1). Z olefinic analogues (e.g. 11) were usually more potent than their E-isomers (e.g. 12). Structure-activity relationships are discussed in detail. PMID- 8457151 TI - Somatostatin analogue inhibits intestinal regeneration. AB - Somatostatin analogue octreotide inhibits intestinal absorption and motility but its effect on epithelial cell migration and proliferation remains unclear. Our aim was to determine the effect of octreotide on parameters of intestinal regeneration, including epidermal growth factor (EGF)-induced changes. Thirty rabbits had full-thickness ileal defects patched with cecal serosa surface. Group 1 were controls. Groups 2 and 3 received 100 micrograms and 1000 micrograms, respectively, of subcutaneous octreotide daily. Group 4 received EGF at 1.5 micrograms/kg per hour via subcutaneous miniosmotic pump, and group 5 received both octreotide (1000 micrograms/d) and EGF (1.5 micrograms/kg per hour). Octreotide at 100 micrograms/d did not inhibit epithelial cell migration or proliferation at 7 days. Octreotide at 1000 micrograms/d inhibited normal but not EGF-stimulated cell migration. Octreotide decreased EGF-stimulated but not normal proliferation. Octreotide impairs epithelial cell migration in a dose-dependent manner. Octreotide inhibits EGF-stimulated proliferative activity but not EGF stimulated migration. Prolonged administration of octreotide may adversely affect normal and adaptive intestinal regeneration by both direct and indirect effects. PMID- 8457152 TI - Intraoperative radiotherapy in retroperitoneal sarcomas. Final results of a prospective, randomized, clinical trial. AB - Thirty-five patients with surgically resected sarcomas of the retroperitoneum were enrolled in a prospective, randomized, clinical trial comparing 20-Gy intraoperative radiotherapy in combination with postoperative low-dose (35- to 40 Gy) external-beam radiotherapy with postoperative high-dose (50- to 55-Gy) external-beam radiotherapy alone. Chemotherapy with doxorubicin hydrochloride, cyclophosphamide (anhydrous), and methotrexate sodium was used for a portion of the trial. Fifteen patients who received intraoperative radiotherapy and 20 control patients were followed up for a minimum of 5 years (median follow-up, 8 years). Median survival times were similar for the group that received intraoperative radiotherapy (45 months) and the control group (52 months). There were no indications of benefit from adjunctive chemotherapy. The number of locoregional recurrences was significantly lower among those who received intraoperative radiotherapy (six of 15) than control patients (16 of 20). Patients who received intraoperative radiotherapy had fewer complications of disabling radiation-related enteritis (two of 15) than control patients (10 of 20), but radiation-related peripheral neuropathy was more frequent among those who received intraoperative radiotherapy (nine of 15) than among control patients (one of 20). PMID- 8457153 TI - Manometry of individual segments of the distal esophageal sphincter. Its relation to functional incompetence. AB - The major components of the lower esophageal sphincter, the pressure it exerts, its total length, and the length of sphincter affected by abdominal pressure are usually expressed as means of several recordings from different radial segments of the sphincter. In segmental manometry, the individual readings for these components in each segment, rather than the mean values, are analyzed. We used segmental manometry to study 50 normal volunteers and 200 patients with symptoms suggestive of gastroesophageal reflux. Of the latter, 100 had increased esophageal acid exposure and 100 did not. An increased number of defective segments was associated with a greater prevalence of increased esophageal acid exposure. Segmental analysis disclosed the same number (52) of defective sphincters (defined as sphincters with two or more defective segments) in the 100 patients with increased acid exposure as did standard analysis. However, the relationship between a defective lower esophageal sphincter and the number of reflux episodes was clearer when a defective sphincter was defined using standard analysis. Segmental analysis of the lower esophageal sphincter has no clear advantage over standard analysis. PMID- 8457154 TI - Polytetrafluoroethylene grafts in infrainguinal arterial revascularization. Factors affecting outcome. AB - One hundred thirty-seven polytetrafluoroethylene infrainguinal bypass grafts were performed over 2 years. The results were analyzed using univariate and multivariate analyses. Our operative mortality was 3.2% and the post-operative amputation rate was 5.8%. Forty-eight reconstructions were done for claudication, with a 5-year secondary patency rate of 64%, no early amputations, and a 2.9% (one limb) late amputation rate. Sixty-six reconstructions were done for rest pain with a 5-year secondary patency rate of 58% and a 3-year limb salvage rate of 77%. The 5-year secondary patency rate for 23 patients with trophic changes was 30%, and the 3-year limb salvage rate was 71%. Multivariate analysis identified the ankle-brachial index as the most important independent factor predicting both primary and secondary graft patency. The cumulative primary and secondary patency rates for patients with an ankle-brachial index of less than 0.5 at 78 months was 37% and 46%, respectively; and 57% and 68%, respectively for patients with an ankle-brachial index of 0.5 or more. PMID- 8457155 TI - Diaphragm function is not impaired by pneumoperitoneum after laparoscopy. AB - Open cholecystectomy is known to induce a major restrictive respiratory syndrome. These respiratory disturbances, although of reduced magnitude, still persist after laparoscopic cholecystectomy. To determine the role of pneumoperitoneum per se in the respiratory dysfunction observed after this procedure, seven patients were studied before and 2 hours after laparoscopy. This diagnostic procedure avoids the upper midline incision and the surgical injury of cholecystectomy. Ventilatory performance and diaphragm function were assessed as follows: (1) during quiet tidal breathing by obtaining measurements of esophageal, gastric, and transdiaphragmatic pressures; determining the ratio of gastric pressures to esophageal pressures; and abdomen-rib cage partitioning of tidal volume obtained from two differential linear transformers and (2) during maximal respiratory efforts by obtaining measurements of vital capacity and maximal transdiaphragmatic pressure during Muller's maneuver and a sniff test. Although a large residual pneumoperitoneum (assessed as the maximal height of the suprahepatic space: Hmax = 30.3 +/- 7.8 mm) was observed after laparoscopy, we did not find any change suggestive of diaphragm dysfunction. We thus conclude that postoperative residual pneumoperitoneum per se is unable to explain the diaphragm dysfunction observed after open or laparoscopic cholecystectomy. PMID- 8457156 TI - Solid and papillary neoplasm of the pancreas. Emphasis on surgical treatment. AB - Six Chinese females with solid and papillary neoplasms of the pancreas underwent surgery. Mean age was 26 years. The most common clinical sign was a large palpable abdominal mass. One patient presented with shock and acute onset of abdominal pain with positive peritoneal signs due to rupture of the tumor. The surgical procedures included Whipple's operation in one patient with a tumor at the head of pancreas, a 75% distal pancreatectomy in two patients with tumor of the body or tail of the pancreas, a partial pancreatectomy and pancreaticogastrostomy in one patient with a tumor at the neck and body of the pancreas, total excision in one patient with a tumor of the body of the pancreas, and a Roux-en-Y cystojejunostomy in one patient with a huge unresectable tumor of the head and body of the pancreas. During the follow-up period of from 40 to 83 months, four patients had survived and two had died of causes unrelated to the tumor in the differential diagnosis of a pancreatic mass, especially in young women with long histories of epigastric masses. Resection is the treatment of choice when the tumor is resectable. For unresectable tumors, a bypass procedure might be an alternative. PMID- 8457157 TI - Experience with ambulatory preoperative bowel preparation at the Johns Hopkins Hospital. AB - A transition to ambulatory preoperative antibiotic bowel preparation was carried out. The protocol included a liquid diet for 40 hours preceding surgery and coordination of purging with buffered oral saline laxative, 45 mL containing 8 g sodium phosphate and 22 g sodium biphosphate (Fleet Phospho-Soda, C.B. Fleet Co, Lynchburg, Va) and bisacodyl preparation with an oral erythromycin base-neomycin routine. Enemas were omitted. Personnel in the preoperative evaluation center had the responsibility of instructing patients, distributing directions and drugs, and reviewing for compliance and possible problems during the preoperative period. All patients scheduled for any of a variety of gastrointestinal procedures, as well as some other complex operations, were included in this study. Follow-up data were obtained. Surgeons' comments regarding efficacy were highly favorable. In only five cases was there comment regarding liquid stool, and this was no impediment to surgery. This incidence was comparable with that of the inpatient experience, as was the spectrum of postoperative complications. Transfer of responsibility to the department proceeded with ease. Results were entirely comparable with those of the former inpatient experience. PMID- 8457158 TI - The economic impact of infections. An analysis of hospital costs and charges in surgical patients with cancer. AB - We performed an economic analysis of the care provided to patients undergoing major abdominal surgical procedures to determine the effect of postoperative infection on hospital resource use. Patients' clinical and demographic characteristics and their use of medical care services were determined from a review of hospital bills and medical records. Hospital charges were obtained from the hospital billing system and costs were determined by use of Medicare cost charge ratios obtained from the hospital's Medicare Cost Report. The care of patients with postoperative infections was significantly more expensive than that of uninfected patients (multivariate analysis indicated that a surgical infection added $12,542 to the cost of patient care). Patients with postoperative fever but without documented infection were also more expensive to care for than afebrile, uninfected patients (fever added $9145 to the cost of care). Increased costs for infected patients were found among microbiology tests, radiology services, pharmaceutical costs, and room costs. For these patients, we found that use of departmental cost-charge ratios, instead of hospital-wide cost-charge ratios, had no substantial impact on comparison of the cost of care for infected and uninfected patients. PMID- 8457159 TI - Intestinal permeability after severe trauma and hemorrhagic shock is increased without relation to septic complications. AB - After thermal injury, alterations in intestinal permeability have been demonstrated and have correlated with subsequent infections. We measured intestinal permeability on the second day after severe trauma and hemorrhagic shock (ruptured abdominal aneurysm). The mean (+/- SD) lactulose-mannitol (L/M) excretion ratio was 0.012 +/- 0.005 in seven healthy control subjects, 0.069 +/- 0.034 in 11 severely traumatized patients, and 0.098 +/- 0.093 in eight patients with aneurysm, indicating a significant increase of intestinal permeability in both patient groups. No significant correlation was found between L/M ratios and age, severity of injury or shock, lactate levels on admission, APACHE (acute physiology and chronic health evaluation) II score, daily pulmonary gas exchange parameters, or mean multiple organ failure scores. No difference in intestinal permeability between patients with and without subsequent infections could be demonstrated. In 11 patients we looked for endotoxin in the systemic circulation. In six patients endotoxemia was present immediately after admission and before the L/M test. However, during the L/M test and 1 day afterward no circulating endotoxin was observed. The present data provide evidence for the hypothesis that increased intestinal permeability and subsequent infectious complications are independent phenomena, frequently seen in patients after severe trauma or hemorrhagic shock. PMID- 8457160 TI - Railway surgery. Traumatology and managed health care in 19th-century United States. AB - Railway surgery was an organized movement in the late 19th century that had as its primary goal the systematic study of accident or trauma surgery. Railway surgeons, although often regarded with contempt by their fellow physicians, fostered such revolutionary concepts in health care provision as private inpatient hospitals and rudimentary managed care plans. Railway surgery and its proponents are a long-forgotten chapter in the history of US surgery, but they serve as an apt example of how studying and understanding the past can enable us to be better prepared to cope with the present and the future. PMID- 8457161 TI - Intestinal perforation from gastrointestinal histoplasmosis in acquired immunodeficiency syndrome. Case report and review of the literature. AB - Gastrointestinal involvement with histoplasmosis in patients with the acquired immunodeficiency syndrome is a rare but documented phenomenon. Most patients present with diarrhea, fever, and abdominal pain. We present a case of a woman who tested positive for the human immunodeficiency virus antibody who developed an intestinal perforation due to Histoplasma capsulatum of the ileum. The patient, whose only risk factor was a blood transfusion 8 years earlier, had been previously diagnosed as having disseminated histoplasmosis with gastrointestinal involvement. While receiving oral antifungal treatment (itraconazole), she developed two separate areas of ileal perforation due to H capsulatum. Complications from gastrointestinal involvement with histoplasmosis, such as perforation, should be considered in patients infected with the human immunodeficiency virus with signs and symptoms suggesting abdominal disease. PMID- 8457162 TI - Foreign bodies within a Meckel's diverticulum. PMID- 8457163 TI - The fate of the spilled gallstone. PMID- 8457164 TI - [Efficacy of long-term beclomethasone dipropionate inhalation therapy in pediatric patients with asthma, and its effect on height growth and adrenocortical functions]. AB - Seventy-eight pediatric patients with moderate to severe chronic asthma, aged 6 to 16 years, who failed to respond well to inhaled DSCG and theophylline RTC, were treated with beclomethasone dipropionate inhaler (BDI) for 0.5 to 10 years (mean: 4.2 +/- 2.4 years). The efficacy rate gradually increased with time: 61.1% at one year after the start of the treatment and 89.5% at three years. Long-term BDI therapy over five years did not cause suppression of height growth or adrenocortical functions (early morning cortisol level and rapid ACTH test). However, the safety of long-term BDI therapy in children still needs to be studied more thoroughly and established. Further investigation will be necessary since some cases did not respond to BDI therapy while others died of exacerbated asthmatic symptoms soon after the start of BDI therapy. PMID- 8457165 TI - [Study on the inhibitory effect of AA-2414 on platelet aggregation and its clinical effect in asthmatic patients]. AB - We previously reported that AA-2414, an eicosanoid receptor antagonist, inhibits platelet aggregation mediated by TXA2/PGH2 receptors in patients with bronchial asthma, but that the inhibitory effects differ among individuals. In this study, we measured the in vitro inhibition rate of platelet aggregation by AA-2414 using U-46619 as an aggregating agent in 22 asthmatic patients and classified them into Group A (showing an inhibition rate of 60% or more) and Group B (showing a rate of less than 60%). Subsequently, AA-2414 tablets (40 mg/day) were orally administered to both groups for 6 weeks, and the clinical effects were compared. A positive correlation was observed between the in vitro U-46619-induced platelet aggregation rate and the inhibition rate of aggregation by AA-2414. At the end of administration, marked inhibition of U-46619-induced platelet aggregation was observed in all patients. However, Group A showed a higher improvement rate of symptoms than Group B. Asthmatic patients can be classified into the groups showing good or poor platelet responses. The response may reflect reactivity to TXA2 in the local airway. PMID- 8457166 TI - [Bronchial reactivity to methacholine and serotonin in six inbred mouse strains]. AB - We examined six mouse strains, A/J, DBA/2, WBB6F1-W/Wv, WBB6F1- +/+, C3H/HeN, C57BL/6, for their bronchial reactivity to methacholine and serotonin. The mice were anaesthetized with intraperitoneal sodium pentobarbital. The trachea was intubated and one jugular vein was cannulated. Then, the mice were ventilated on air, using a small animal ventilator at a rate of 60 strokes/min with a tidal volume of 0.5 ml. Methacholine and serotonin diluted to various concentrations were administered intravenously. Bronchoconstriction was assessed by the modified Konzett-Rossler method. According to their bronchial responsiveness to methacholine and serotonin, the strains were grouped into high- (A/J, DBA/2), middle- (WBB6F1-W/Wv, -+/+) or low- (C3H/HeN, C57BL/6) responder groups. PMID- 8457167 TI - [A case of severe milk allergy. Relationship with type I and Type III allergic reactions]. AB - A case of cow's milk allergy related to type I and type III allergic reactions is reported. The patient is a one-month-old girl. She had watery diarrhea and abdominal distention soon after commencement of milk feeding two weeks after birth. She was cyanotic and floppy on admission. Intravenous complete hyperalimentation was tried to combat her diarrhea with good clinical effect. Then feeding with 605Z milk (enzyme digested cow's milk antigen, Meiji Milk Products Co., Ltd.) was started, and the diarrhea improved. Laboratory findings showed positive milk PK test, elevated IgE score, and positive milk specific RAST score, decreased serum complement, elevated levels of each immunoglobulin class of milk specific antibodies, especially milk specific IgG1 antibody and increased complement absorption test. She was diagnosed as having milk allergy related to both type I and type III allergies from the above-mentioned results. Specific antibodies were diminished after feeding with 605Z. Although her mother had not taken cow's milk over the past 10 years, she took a lot of milk during her pregnancy. But her serum milk specific antibodies were not elevated. It was suggested that the baby's antibodies were not derived from her mother but that the baby produced them by herself. PMID- 8457168 TI - [IgE-receptor stimulation induces biphasic 1,2-diacylglycerol production in RBL 2H3 cells. Phosphatidylcholine hydrolysis by phospholipase D plays a major role in the second sustained 1,2-diacylglycerol accumulation]. AB - Activation of RBL-2H3 cells by cross-linking their IgE receptors resulted in a biphasic increase in cellular 1,2-diacylglycerol (DG) content. The first-phase DG production was coincident with a transient breakdown of phosphatidylinositol 4,5 bisphosphate (PIP2). The second large sustained phase of DG accumulation appeared to be derived mainly from phosphatidylcholine (PC) and partly from phosphatidylinositol (PI). The accumulation of phosphatidylethanol (PEt) and the reduction of DG formation in the presence of ethanol suggested that more than 50% of the DG due to PC hydrolysis was formed through the action of phospholipase D. The addition of phorbol myristate acetate or Ca2+ ionophore A23187 stimulated the hydrolysis of PC. In protein kinase C (PKC) down-regulated cells, PC hydrolysis induced by A23187 was markedly suppressed. Taken together, these results lead as to speculate that hydrolysis of PC is regulated by the increase in cellular Ca2+ and PKC activation through the hydrolysis of PIP2. The exocytotic response became evident with a 1 min time lag after antigen (Ag) stimulation, followed by the transient breakdown of PIP2. Ethanol inhibited Ag-stimulated serotonin secretion. The concentration-dependent inhibitory profile of secretion by ethanol correlated well with that of the sustained phase of DG accumulation. These results suggest that sustained DG production, mainly derived from PC through phospholipase D action, plays an important role in maintaining secretory response. PMID- 8457169 TI - [Effects of Perilla frutescens extract on anti-DNP IgE antibody production in mice]. AB - Perilla frutescens is a Chinese herbal medicine. In this study, we prepared an extract of Perilla frutescens (PFE) and examined its effects on anti-DNP antibody responses in mice. The mice were immunized with DNP-ovalbumin in Alum adjuvant. To examine the effects of PFE on primary antibody responses, PFE was intraperitoneally injected the day before primary immunization. Anti-DNP IgE antibody production was found to be markedly suppressed by PFE injection. Then, we examined the effects on secondary antibody responses. PFE was injected only the day before secondary immunization. Anti-DNP IgE production was markedly suppressed, but IgG response was not so affected. These results suggest that the immunosuppressive effects of PFE are preferentially on IgE production and that PFE may be useful for the suppression of IgE antibody in certain allergic disorders. PMID- 8457170 TI - [A study of characteristics in adult asthmatics who are sensitized by cats and dogs allergens]. AB - We studied adult asthmatics who were sensitized (RAST sore > or = 1) by cats and dogs allergens. Compared with non-sensitized asthmatics, the following some characteristics were noted in the sensitized asthmatics: 1) The histogram of the onset age of asthma showed two peaks. 2) The asthmatics sensitized by cats epithelium were more frequent and had higher RAST scores than those sensitized by dog hair dander. 3) There was a significant correlation between the RAST scores to dogs dander and dog hair. 4) There was no correlation between the RAST score to cat epithelium and dog hair. 5) The positive rations of intradermal testing to other allergens were higher in the sensitized asthmatics than in the non sensitized asthmatics, especially to some foods allergens. 6) The asthmatics sensitized by cat and dog allergens were much more sensitized by house-dust mites than were the non-sensitized asthmatics. The asthmatics sensitized by cat and dog demonstrated being allergic to not only cat and dog allergens but also to many other allergens. We thought that the sensitized asthmatics were more atopic than the non-sensitized asthmatics and this was the reason why they were sensitized by cat and dog. The RAST scores to cat allergens were higher than the RAST scores to dog allergens. This fact showed that the cat was more important than the dog. This result agreed with our clinical experience. PMID- 8457172 TI - Veterinary practice in South Australia. PMID- 8457171 TI - Effects of a controlled-release albendazole capsule on parasitism and production from grazing Merino ewes and lambs. AB - Effects of a controlled-release albendazole capsule (CRC) on nematode parasitism and production of Merino ewes and lambs were investigated in a replicated grazing experiment between August 1986 and July 1989. The experiment was conducted on a site where the naturally occurring parasites were benzimidazole-resistant, with double the recommended dose of oxfendazole reducing faecal egg counts of Trichostrongylus colubriformis by less than 50%. Two CRC treatments were compared with a minimal treatment control and the widely-used strategic control program, Wormkill. Egg counts and worm burdens of major parasite species of ewes and of lambs before and after weaning were significantly reduced by use of the CRC in ewes before lambing or in lambs at weaning. These parasitological effects were reflected in increased productivity of CRC ewes and lambs. Ewes given CRCs lost less weight and grew more wool during lactation than ewes given Wormkill or control treatments, while their lambs gained more weight and had heavier fleeces than lambs from Wormkill or control treatments. Where lambs were weaned by removing ewes from the lambing paddock, administration of the CRC at weaning to lambs whose dams had also been treated with the CRC did not result in improved production when compared with lambs from ewes dosed with CRCs and treated after weaning according to the Wormkill program. Some possible uses for the CRC in ewes and lambs were identified. PMID- 8457173 TI - An outbreak of Akabane virus-induced abnormalities in calves after agistment in an endemic region. AB - During 1988, 2 farmers in the Bega district agisted pregnant cattle in the Hunter Valley of New South Wales. On return to the district to calve, 54% of calves from herd 1 and 30% of calves from herd 2 were affected with congenital arthrogryposis or hydranencephaly caused by Akabane virus infection. Field observations and laboratory findings from this outbreak are presented, illustrating the danger of moving immunologically naive animals into areas where Akabane virus is endemic. PMID- 8457174 TI - Residues of endosulfan in the tissues of lactating goats. AB - The sites of tissue accumulation in lactating goats of the organochlorine insecticide endosulfan were studied. Twelve lactating goats were dosed orally with endosulfan (1 mg/kg body weight per day) for 28 days. Groups of 3 animals were killed on days 1, 8, 15, and 21 after endosulfan treatment ended and their tissues examined for the presence of endosulfan. Total residues of alpha and beta endosulfan and endosulfan sulphate (mg/kg) were detected in kidney (0.29), gastro intestinal tract (0.20), liver (0.12), brain (0.06), muscle and spleen (0.04), lung and heart (0.01) and milk (0.02) on the first sampling day but within 15 days, concentrations had fallen to < 0.01 mg/kg in all tissues except kidney (0.20). Endosulfan could not be detected in animals 21 days after dosing had ceased. The residue in milk could only be detected on day 1 of sampling. This study indicates that kidney rather than fatty tissue should be used to monitor the presence of endosulfan in animals intended for human consumption. PMID- 8457175 TI - The survival of platypus in captivity: a reappraisal with recommendations for veterinary management and future research. AB - Data are presented on the duration of survival of platypus held in the collections of the 5 Australian zoos displaying the species over the period 1987 1991. Of 10 living platypus, five had survived for 7 or more years. Similarly, of 10 captive animals that died during the period, six had survived for 6 or more years. Five purpose-caught animals were integrated into captive collections over the period; all of these were alive at the end of 1991. The high survival of captive platypus documented in this study contrasts with the conclusion of Whittington (1991) that the duration of survival of platypus in captivity is generally short. This primarily reflects differences in the nature of the two sets of data: Whittington's analysis was based on incomplete records dating back to 1934, and also categorised as 'managed in captivity' those wild platypus that died at zoos while under veterinary care. A series of recommendations on current captive management issues includes the need for improved veterinary knowledge of platypus. PMID- 8457176 TI - Iridovirus-like virions in imported dwarf gourami (Colisa lalia) with systemic amoebiasis. PMID- 8457177 TI - Cerebellar abiotrophy in Angus cattle. PMID- 8457178 TI - Hepatic vasculopathy and encephalopathy in Brahman-type calves. PMID- 8457179 TI - Pathology of Mycoplasma serogroup 11 induced mastitis in sheep. PMID- 8457180 TI - Aberrant behaviour in a bitch with a granulosa-theca cell tumour. PMID- 8457181 TI - Ovine hereditary chondrodysplasia (spider syndrome) in Suffolk lambs. PMID- 8457182 TI - A survey of Libyostrongylus douglassi on ostrich farms in eastern Victoria. PMID- 8457183 TI - Fixed-time insemination for controlled breeding of Bos indicus heifers under extensive management conditions in north Queensland. PMID- 8457184 TI - [Testing of a new bait for the oral immunization of red foxes (Vulpes vulpes) against rabies]. AB - A field trial is described for testing the acceptance of a new machine made bait (ALTROFOX/91) for oral immunization of red foxes. The investigations were undertaken in direct comparison with a bait with known attractiveness for foxes. After the choice of suitable field trial areas the baits were distributed at a density of 18/km2 by fixed-wing aircraft. Each bait version contained a different derivate of tetracycline as a biomarker. The evaluation of the attractiveness and acceptance by red foxes and non target species was established by visual controls on the third, seventh and 14th day after distribution and biomarker proving in bone specimens of investigated animals. PMID- 8457185 TI - [Chronic gastritis caused by Ollulanus tricuspis (Leuckart, 1865) in a tiger]. AB - A chronic gastritis caused by an infestation with O. tricuspis is described. The differential-diagnostic importance of this parasitosis in chronic maldigestive diseases is emphasized. Conventional coproscopic diagnostic procedures fail as the life cycle of the parasite is confined to the gastrum of the host. PMID- 8457186 TI - [Possible prognostic criteria for the evaluation of the susceptibility to septic diseases increased by stress in swine]. AB - A test to assess leukocyte function developed in our laboratory and based on effector mediated alterations in the cell volume was applied to study the effect of stress on the immune status of pregnant pigs. Effectors selected were prolactin, opsonized particles (Zymosan) and Zymosan together with the autologous plasma. The pigs were exposed to two stress situation: 1. fixation for an ear vein catheterization and 2. injuries by laparotomy. The investigations demonstrated that--following the stress situation 1--the effector induced alterations in the cell volume gave an indication of the susceptibility to septic inflammatory processes subsequent to the laparotomy (stress situation 2) which was carried out about 1 week after the fixation (stress situation 1). Measuring the humoral immunocompetence CRP, C3c, alpha-2-macroglobulin levels in the blood plasma had no or little prognostic value concerning the susceptibility to or the onset of the disease. PMID- 8457187 TI - [Sexual behavior of muscovy ducks under conditions of intensive husbandry of adult animals: dependence on the time of day, husbandry conditions, body mass and health status]. AB - Sexual behaviour of muscovy ducks kept under intensive husbandry conditions is described comprehensively. To characterize the sexual activity qualitatively four different categories were used. It could be demonstrated a typical diurnal rhythm of mating activity with a maximum in the afternoon. The mating activity was diminished also at the end of the laying period. Body mass as well as state of health have an influence on quality and quantity of mating activity. Body weight, mating activity and size of foot pads are correlated with each other; the higher the body weight the higher the size of foot pads and the lower the mating activity. Besides of this, the mating activity is influenced by keeping conditions and genetic factors. PMID- 8457188 TI - [Domestic animals and veterinary medicine in the Old and New Testaments of the Bible and the Apocrypha]. AB - Referring to an 1865 edition of the Bible, the article deals with domestic animals and veterinary matters in the sacred book of Christianity, singling out donkey, camel, horse, sheep, goat, pig, dog and cat. Comments on early aspects of animal welfare and food hygiene round off the picture. PMID- 8457189 TI - Nuclear diacylglycerol is increased during cell proliferation in vivo. AB - Highly purified nuclei were prepared from livers and kidneys of rats undergoing compensatory hepatic or renal growth, the former being predominantly by cellular proliferation, and the latter mostly by cellular enlargement. In liver, an increase in nuclear diacylglycerol (DAG) concentration occurred between 16 and 30 h, peaking at around 20 h. At the peak of nuclear DAG production a specific translocation of protein kinase C to the nucleus could be detected; no such changes occurred in kidney. There was no detectable change in whole-cell DAG levels in liver, and the increase in DAG was only measurable in nuclei freed of their nuclear membrane. Overall, these results suggest that there is a stimulation of intranuclear DAG production, possibly through the activation of an inositide cycle [Divecha, Banfic and Irvine (1991) EMBO J. 10, 3207-3214] during cell proliferation in vivo. PMID- 8457190 TI - Phenobarbital induction of AP-1 binding activity mediates activation of glutathione S-transferase and quinone reductase gene expression. AB - Phenobarbital is an inducer of xenobiotic-metabolizing enzymes, such as cytochrome P-450, glutathione S-transferases (GSTs) and NAD(P)H:quinone reductase, as well as being a promoter of hepatocarcinogenesis. The molecular mechanisms regulating these biological activities are, however, unknown. In this paper we show that induction by phenobarbital of GST Ya and quinone reductase gene expression is mediated by regulatory elements, EpRE and ARE respectively, which are composed of two adjacent AP-1-like binding sites. EpRE was recently found to be activated by a Fos/Jun heterodimeric complex (AP-1). Here we show that phenobarbital induces an increase in AP-1 binding activity in nuclear extracts of cultured hepatoma cells. Furthermore, we observe that the induction of chloramphenicol acetyltransferase (CAT) activity from an EpRE Ya-cat gene construct and of AP-1 binding activity by phenobarbital is inhibited by the thiol compounds N-acetyl-L-cysteine and glutathione. These results suggest that the phenobarbital induction of AP-1 activity, leading to the AP-1-mediated transcriptional activation of the GST Ya and quinone reductase genes, may involve production of reactive oxygen species and an increase in intracellular oxidant levels, which is prevented by thiol compounds. In view of the involvement of AP-1 in the control of cell proliferation and transformation, the induction by phenobarbital of AP-1 binding activity observed here provides a possible molecular mechanism for the tumour-promoting activity of this drug. PMID- 8457191 TI - Age-related changes in expression of the neural cell adhesion molecule in skeletal muscle: a comparative study of newborn, adult and aged rats. AB - Neural cell adhesion molecule (NCAM) is expressed by muscle and involved in muscle-neuron and muscle-muscle cell interactions. The expression in muscle is regulated during myogenesis and by the state of innervation. In aged muscle, both neurogenic and myogenic degenerative processes occur. We here report quantitative and qualitative changes in NCAM protein and mRNA forms during aging in normal rat skeletal muscle. Determination of the amount of NCAM by e.l.i.s.a. showed that the level decreased from perinatal to adult age, followed by a considerable increase in 24-month-old rat muscle. Thus NCAM concentration in aged muscle was sixfold higher than in young adult muscle. In contrast with previous reports, NCAM polypeptides of 200, 145, 125 and 120 kDa were observed by immunoblotting throughout postnatal development and aging, the relative proportions of the individual NCAM polypeptides remaining virtually unchanged at all ages examined. However, changes in the extent of sialylation of NCAM were demonstrated. Even though the relative amounts of the various NCAM polypeptides were unchanged during aging, distinct changes in NCAM mRNA classes were observed. Three NCAM mRNA classes of 6.7, 5.2 and 2.9 kb were present in perinatal and young adult skeletal muscle, whereas only the 5.2 and 2.9 kb mRNA classes could be demonstrated in aged muscle. This indicates that metabolism of the various NCAM polypeptides is individually regulated during aging. Alternative splicing of NCAM mRNA in skeletal muscle was studied by Northern blotting using DNA oligonucleotide probes specifically hybridizing to selected exons or exon combinations. Exon VASE, which has previously been shown to be present in both brain and heart NCAM mRNA, was virtually absent from skeletal muscle at all ages studied. In contrast, the majority of NCAM mRNA in postnatal skeletal muscle was shown to contain extra exons inserted between exons 12 and 13. Of the various possible exon combinations at this splice site, the combinations 12-a-AAG-13 and 12-a-b seemed to be prevalent in postnatal skeletal muscle. No significant change in the relative proportion of these two exon combinations occurred during aging. The observed upregulation of NCAM protein in aged muscle supports the assumption that an increasing proportion of muscle fibres are denervated in aged muscle. Selective upregulation of the 5.2 and 2.9 kb mRNA forms have previously been demonstrated in muscle cell lines and in primary cultures of muscle cells during formation of myotubes in vitro, and this switch in NCAM mRNA classes has been suggested to correlate with myogenesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457192 TI - Transcriptional regulation of hydroxyindole O-methyltransferase in the chicken pineal gland: day/night changes and long-term effects of light and darkness. AB - The indolic hormone melatonin is produced by the pineal gland according to a daily rhythm. The terminal step of melatonin synthesis is catalysed by hydroxyindole O-methyltransferase (HIOMT, EC 2.1.1.4). Adaptation to constant light or darkness modifies HIOMT activity and concentration. Using a cDNA probe encoding HIOMT, we investigated the effect of environmental lighting on HIOMT gene expression in the chicken pineal gland. HIOMT mRNA levels increased by 100% in constant light as compared with constant darkness. In addition, the present study disclosed the existence of a day/night rhythm of HIOMT gene transcription, with 3-fold higher mRNA levels at midday than at midnight. This transcriptional rhythm was not accompanied by day/night changes in HIOMT concentration, probably due to a slow turnover of this protein. Unexpected darkness did not prevent the daytime rise in HIOMT mRNA levels, whereas unexpected light prevented the night time fall in HIOMT mRNA levels. Together, the data would suggest that the day/night rhythm of HIOMT gene transcription in the chicken pineal gland involves both a response to light and the activity of a biological oscillator. PMID- 8457193 TI - Evidence for common structural changes in thrombin induced by active-site or exosite binding. AB - The gamma-loop of thrombin is a flexible, surface-accessible loop in free thrombin that appears to be one of several sites participating in the interaction of the enzyme with macromolecular substrates and inhibitors. Using limited proteolysis and intrinsic fluorescence measurements, we have studied changes in thrombin structure induced by small, site-specific ligands. Binding of a C terminal peptide of hirudin to the anion-binding exosite of thrombin induced a structural change in the gamma-loop, which caused a 6-fold reduction in the susceptibility of the enzyme to limited proteolysis by elastase and chymotrypsin. Binding of several active site-specific thrombin inhibitors conferred an even greater protection from proteolysis at the gamma-loop. For example, the covalent complex of thrombin with D-Phe-Pro-Arg-CH2Cl was 95-fold less susceptible to cleavage by chymotrypsin than the free enzyme. Furthermore, binding of either exosite or active-site probes induced a common intrinsic fluorescence change in thrombin (a fractional increase of 0.13). These results are surprising because crystallographic studies indicate that direct contact between the bound probes and relevant residues of the gamma-loop is very unlikely. Thus we have identified an allosteric interaction that couples the active site of thrombin to the gamma loop. An interaction of this nature may be one way in which thrombomodulin modulates the reactivity of thrombin. PMID- 8457194 TI - Phosphorylation of adenosine in anoxic hepatocytes by an exchange reaction catalysed by adenosine kinase. AB - The elevation of adenosine levels induced by anoxia in isolated rat hepatocytes has been shown to result mainly from an arrest of the recycling of the nucleoside by adenosine kinase [Bontemps, Vincent and Van den Berghe (1993) Biochem. J. 290, 671-677]. To assess the activity of the latter enzyme in intact hepatocytes, incorporation of radioactive adenosine into the cells' adenine nucleotides was measured. Unexpectedly, despite the near-absence of ATP in anoxic cells, 40% of 50 microM [8-14C]adenosine was still incorporated into adenylates over 5 min. Moreover, whereas unlabelled and labelled adenosine were utilized in parallel in normoxic cells, uptake of [8-14C]adenosine did not correspond to a net disappearance of adenosine in anoxic cells. Addition of 1 mM unlabelled adenosine to anoxic hepatocytes in which the adenine nucleotides had been prelabelled with [U-14C]adenine induced an immediate loss of their radioactivity. The latter was recovered in the form of adenosine, but the size of the adenylate pool was not modified. Taken together, these results suggest the occurrence of an exchange reaction between AMP and adenosine. Incubation of Sephadex G-25-filtered high speed supernatants of rat liver with 20 microM [8-14C]adenosine, 10 mM MgCl2 and 1 mM AMP resulted in the labelling of AMP in the total absence of ATP. This labelling was influenced by effectors of both adenosine kinase and cytosolic IMP GMP 5'-nucleotidase; the latter is known to catalyse an exchange reaction [Worku and Newby (1982) Biochem. J. 205, 503-510]. Chromatography of cytosolic fractions of rat liver on DEAE-Sepharose, followed by Sephacryl S-200 and AMP-Sepharose, demonstrated that the exchange reaction between adenosine and AMP co-purified with adenosine kinase. It is concluded that incorporation of labelled adenosine into adenine nucleotides should not be considered to be proof of adenosine kinase activity in anoxia. PMID- 8457195 TI - Differential feedback regulation of cholesterol 7 alpha-hydroxylase mRNA and transcriptional activity by rat bile acids in primary monolayer cultures of rat hepatocytes. AB - We have used primary monolayer cultures of rat hepatocytes to study the effects of physiological concentrations of various bile acids, commonly found in bile of normal rats, on the mechanism of regulation of cholesterol 7 alpha-hydroxylase and bile acid synthesis. Addition of taurocholic acid, the most predominant bile acid in rat bile, to the culture medium suppressed cholesterol 7 alpha hydroxylase activity and mRNA time- and dose-dependently. The decrease in enzyme activity paralleled the changes in mRNA. Maximal suppression of cholesterol 7 alpha-hydroxylase mRNA (-91%) and enzyme activity (-89%) was observed after a 16 h incubation period with 50 microM taurocholic acid. The declines in mRNA and enzyme caused by taurocholic acid were tightly coupled and followed first-order kinetics with a half-life of 4 h. Transcriptional activity, as assessed with nuclear run-on assays, was decreased by 44% at 50 microM taurocholic acid. Mass production of bile acids (chenodeoxycholic acid and beta-muricholic acid) was inhibited to a similar extent as the cholesterol 7 alpha-hydroxylase when different concentrations of taurocholic acid were used, giving maximal inhibition (-81%) at 50 microM taurocholic acid. Glycocholic acid and unconjugated cholic acid were equally effective as taurocholic acid in suppressing cholesterol 7 alpha-hydroxylase mRNA. The more hydrophobic bile acids (chenodeoxycholic acid and deoxycholic acid) showed profound suppression of the cholesterol 7 alpha hydroxylase mRNA by 85% and 75% respectively, whereas the other trihydroxy bile acids in rat bile, alpha- and beta-muricholic acid, were not or only marginally active. We conclude that rat bile acids, in particular the more hydrophobic ones, in concentrations commonly observed in portal blood, exert negative feedback control at the level of cholesterol 7 alpha-hydroxylase mRNA in cultured rat hepatocytes through a direct effect on the hepatocytes, and that down-regulation of transcription is only one of the mechanisms involved in this regulation. PMID- 8457196 TI - Iron release and uptake by plant ferritin: effects of pH, reduction and chelation. AB - Ferritins are iron-storage proteins that accumulate in plastids during seed formation, and also in leaves during senescence or iron overload. Iron release from ferritins occurs during growth of seedlings and greening of plastids. Depending on the concentration of the reducing agent ascorbate, either an overall iron release or uptake by ferritins from iron(III) citrate may occur. We have designed methods to measure these simultaneous and independent uptake and release fluxes. Each individual step of the exchange was studied using different iron chelates and an excess of ligand. It is shown that: (i) the chelated form of iron, and not ionic Fe3+, is the substrate for iron reduction, which controls the subsequent uptake by ferritin; (ii) iron uptake by ferritins is faster at pH 8.4 than at pH 7 or 6 and is inhibited by an excess of strongly binding free ligands; and (iii) strongly binding free ligands are inhibitory during iron release by ascorbate. When reactions are allowed to proceed simultaneously, the iron chelating power is shown to be a key factor in the overall exchange. The interactions of iron chelating power, reducing capacity and pH are discussed with regard to their influence on the biochemical mobilization of iron. PMID- 8457197 TI - Kinetic analysis of the liver-type (GLUT2) and brain-type (GLUT3) glucose transporters in Xenopus oocytes: substrate specificities and effects of transport inhibitors. AB - We have expressed the human isoforms of the liver-type (GLUT2) and brain-type (GLUT3) facilitative glucose transporters in oocytes from Xenopus laevis via injection of in vitro transcribed mRNA. As reported previously [Gould, Thomas, Jess and Bell (1991) Biochemistry 30, 5139-5145], GLUT2 mediates the transport of fructose and galactose, and GLUT3 mediates the transport of galactose. We have examined the effects of D-glucose, D-fructose and maltose on deoxyglucose transport in oocytes expressing GLUT2, and D-glucose, D-galactose and maltose on deoxyglucose transport in oocytes expressing GLUT3, and show that each sugar is a competitive inhibitor of transport. Moreover, D-glucose and maltose competitively inhibit fructose transport by GLUT2 and galactose transport by GLUT3, indicating that the transport of the alternative substrates for these transporters is likely to be mediated by the same outward-facing sugar-binding site used by glucose. Cytochalasin B is a non-competitive inhibitor of glucose transport by the well characterized GLUT1 isoform. We show here that cytochalasin B is also a non competitive inhibitor of the transport of deoxyglucose and alternative substrates by GLUT2 and GLUT3 expressed in oocytes. Km and Ki values for each substrate and inhibitor are presented for each isoform, together with further analysis of the binding sites for alternative substrates for these transporter isoforms. PMID- 8457198 TI - Differential targeting of glucose transporter isoforms heterologously expressed in Xenopus oocytes. AB - We have examined the subcellular distribution of three members of the human glucose transporter family expressed in oocytes from Xenopus laevis. Following injection of in vitro-transcribed mRNA encoding the transporter isoform to be studied, we have determined the subcellular localization of the expressed protein by immunofluorescence and by subcellular fractionation coupled with immunoblotting using specific anti-peptide antibodies. We have shown that both the liver-type (GLUT 2) and brain-type (GLUT 3) glucose transporters are expressed predominantly in the plasma membranes of oocytes, and in both cases high levels of glucose transport activity are exhibited. In contrast, the insulin regulatable glucose transporter (GLUT 4) is localized predominantly to an intracellular membrane pool, and the levels of transport activity recorded in oocytes expressing GLUT 4 are correspondingly lower. The localization of the different transporter isoforms to distinct subcellular fractions mirrors the situation observed in their native cell type and thus demonstrates that oocytes may prove to be a useful system with which to study the targeting signals for this important class of membrane proteins. In addition, the determination of the amounts of the transporters expressed per oocyte together with a knowledge of their Km values has allowed us to estimate the turnover numbers of these transporters. Insulin was without effect on glucose transport in oocytes expressing any of these transporter isoforms. Microinjection of guanosine 5' [gamma-thio]triphosphate into oocytes expressing GLUT 4 was also without effect on the transport rate. PMID- 8457199 TI - N.m.r. lipid profiles of cells, tissues and body fluids. Neutral, non-acidic and acidic phospholipid analysis of Bond Elut chromatographic fractions. AB - Although the advantages of in vitro n.m.r. analysis of cellular lipids have been documented, this purely n.m.r. approach also has drawbacks. Rapid and quantitative separation of total lipids into neutral lipids, non-esterified fatty acids, non-acidic phospholipids and acidic phospholipids using Bond Elut ion exchange columns as demonstrated here permitted a more quantitative and complete n.m.r. analysis of glycerides, cholesterol, saturated and unsaturated sphingolipids and ether lipids, as well as of diacylcholine and ethanolamine lipids. Acidic lipids were also analysed. The fatty acid compositions of the intact lipids in each of the four Bond Elut fractions were determined from the n.m.r. spectrum of each fraction. PMID- 8457200 TI - Expression, purification and characterization of B72.3 Fv fragments. AB - The Fv fragment of the antibody B72.3 has been produced by expression in both a mammalian and microbial system, namely Chinese hamster ovary (CHO) cells and Escherichia coli. In both cases secretion of the Fv into the culture medium was achieved, with equivalent amounts of Vh and Vl produced. The yield of Fv from CHO cells was 4 mg/l in roller-bottle culture. E. coli proved to be a more productive system with yields of 40 mg/l in shake flasks rising to 450 mg/l in fermentations. B72.3 Fv from both sources was capable of binding to antigen with similar binding ability to the Fab' fragment. A detailed sedimentation analysis, both by velocity and equilibrium techniques, revealed that the two domains of Fv are associated at high concentrations at pH values close to neutral, but dissociate at concentrations lower than approx. 0.5 mg/ml. Individual Vh or Vl polypeptides are not able to bind to the antigen and thus these results suggest that the antigen promotes assembly of Fv at the low concentrations used in the antigen-binding assays. At a pH value of 1.9, Vh and Vl are completely dissociated even at very high concentrations and are apparently unfolded at low solute concentrations. Small-angle X-ray scattering was used to measure a radius of gyration of 1.75 +/- 0.2 nm (17.5 +/- 2 A) for Fv. PMID- 8457201 TI - Effects of different enzymic treatments on the release of titin fragments from rabbit skeletal myofibrils. Purification of an 800 kDa titin polypeptide. AB - In myofibrils, titin (also called connectin) molecules span from Z line to M line and constitute a third filament system containing an elastic domain in the I band. This giant protein is particularly sensitive to proteolysis in situ. Treatment of rabbit skeletal myofibrils with exogenous proteinases induces a release of titin fragments, which are detected in the soluble myofibrillar fraction. The cleavage of titin occurs at specific points localized at the proximity of Z line and could lead to a concomitant release of alpha-actinin. PMID- 8457202 TI - Characterization of three alleles causing aspartylglycosaminuria: two from a British family and one from an American patient. AB - Aspartylglycosaminuria (AGU) is a lysosomal storage disease principally occurring in Finland that results from mutations in the structural gene for glycosylasparaginase (AGU). This work characterizes the inheritance of two previously reported AGU mutations in a British patient [Ikonen, Aula, Gron, Tollersrud, Halila, Manninen, Syvanen and Peltonen (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 11222-11226]. Use of the PCR determined the glycosylasparaginase cDNA sequence from both parents of the British patient and his AGU-affected brother. The father of the British AGU-affected siblings was found to be a heterozygote carrier for a C-->T point mutation which causes an Ala-->Val amino-acid substitution, while the mother was heterozygous for a 7 bp deletion that results in premature translational termination. The brother of the previously studied patient was similarly shown to be a compound heterozygote. Expression in COS-1 cells revealed the paternal Ala-->Val amino-acid substitution destroyed glycosylasparaginase catalytic activity, prevented transport of the mutant protein to the lysosome, and prevented maturation of the enzyme precursor to its native subunit structure. The Ala-->Val mutation therefore affects glycosylasparaginase in a manner similar to the Finnish AGU Cys-->Ser substitution, further supporting a linkage of glycosylasparaginase catalytic activity to its lysosomal transport and subunit processing [Fisher and Aronson (1991) J. Biol. Chem. 266, 12105-12113]. In addition, a 5 bp deletion mutation from an American patient with AGU has been characterized. The deleted sequence occurs at the beginning of the glycosylasparaginase coding sequence, resulting in an extremely truncated polypeptide. The American 5 bp deletion and the British maternal 7 bp deletion possibly decrease mRNA stability. PMID- 8457203 TI - The structural basis of the inhibition of human alpha-mannosidases by azafuranose analogues of mannose. AB - Eight pyrrolidine, five pyrrolizidine and one indolizidine analogue(s) of the known alpha-mannosidase inhibitor, the azafuranose, 1,4-dideoxy-1,4-imino-D mannitol (DIM), have been tested for inhibition of the multiple forms of alpha mannosidase in human liver in vitro. Substitution of the ring nitrogen markedly decreased or abolished inhibition, but loss of the C-6 hydroxy group, as in 6 deoxy-DIM and 6-deoxy-6-fluoro-DIM, enhanced inhibition, particularly of the lysosomal alpha-mannosidase. Addition of the anomeric substituent-CH2OH decreased inhibition. To be a potent inhibitor of the lysosomal, Golgi II and neutral alpha mannosidases, a polyhydroxylated pyrrolidine must have the same substituents and chirality as mannofuranose at C-2, C-3, C-4 and C-5. These four chiral centres can also be part of a polyhydroxylated indolizidine, e.g. swainsonine, but not of a pyrrolizidine, e.g. cyclized DIM, ring-contracted swainsonine or 1,7-diepi australine. DIM did not inhibit lysosomal alpha-mannosidase intracellularly, but both 6-deoxy-DIM and 6-deoxy-6-fluoro-DIM caused accumulation of partially catabolized glycans in normal human fibroblasts. Analysis of these induced storage products by h.p.l.c. showed that both compounds also inhibited Golgi alpha-mannosidase II and that 6-deoxy-6-fluoro-DIM was also a good inhibitor of the endoplasmic reticulum alpha-mannosidase and specific lysosomal alpha (1-6) mannosidase. None of the mannofuranose analogues appeared to inhibit Golgi alpha mannosidase I. PMID- 8457204 TI - The long-chain sphingoid base of sphingolipids is acylated at the cytosolic surface of the endoplasmic reticulum in rat liver. AB - Ceramide, a key intermediate in sphingolipid metabolism, is synthesized by acylation of sphinganine followed by dehydrogenation of dihydroceramide to ceramide. Using radioactive sphinganine, we have examined the site and topology of dihydroceramide synthesis in well-characterized subcellular fractions from rat liver. [4,5-3H]Sphinganine was introduced as a complex with BSA and was metabolized to [4,5-3H]dihydroceramide upon incubation of rat liver homogenates or microsomes with fatty acyl CoA. Conditions were established in a detergent free system in which dihydroceramide synthesis was not limited by either substrate availability or by amounts of microsomal protein or reaction time. The distribution of dihydroceramide synthesis was found to exactly parallel that of an endoplasmic reticulum (ER) marker upon subfractionation of microsomes, and no endogenous activity was detected in either purified Golgi apparatus or plasma membrane fractions. Limited protease digestion demonstrated that sphinganine N acyltransferase is localized at the cytosolic surface of intact ER-derived vesicles. These results are discussed with regard to the subsequent transport of (dihydro)-ceramide from the ER to sites of further metabolism in a pre-Golgi apparatus compartment and in the cis and medial cisternae of the Golgi apparatus. PMID- 8457205 TI - Identification of G alpha 11 as the phospholipase C-activating G-protein of turkey erythrocytes. AB - A 43 kDa phospholipase C-activating protein has been purified previously from turkey erythrocytes and shown to express immunological properties expected of that of the Gq family of G-protein alpha-subunits [Waldo, Boyer, Morris and Harden (1991) J. Biol. Chem. 266, 14217-14225]. Internal amino acid sequence has now been obtained from this protein which shares 50-100% sequence identity with sequences encoded by mammalian G alpha 11 and G alpha q cDNAs. To identify the purified protein unambiguously, it was necessary to compare its amino acid sequence with the sequence encoded by avian G-protein alpha-subunit cDNA. As such, mouse G alpha q was used as a probe to screen turkey brain and fetal-turkey blood cDNA libraries. A full-length cDNA was identified that encodes avian G alpha 11, on the basis of its 96-98% amino acid identity with mammalian G alpha 11. All eight peptides sequenced from the turkey erythrocyte phospholipase C activating protein are completely contained within the deduced amino acid sequence of the avian G alpha 11 cDNA. Expression of this cDNA in Sf9 cells by using a baculovirus expression system resulted in the production of a 43 kDa protein that reacts strongly with antisera to the Gq family of G-protein alpha subunits and activated purified avian phospholipase C in an AlF4(-)-dependent manner. Taken together, these results unambiguously identify the protein purified from turkey erythrocytes, on the basis of its capacity to activate avian phospholipase C, as G alpha 11. PMID- 8457206 TI - The 17 beta-oestradiol dehydrogenase of pig endometrial cells is localized in specialized vesicles. AB - Two monoclonal antibodies against the 17 beta-oestradiol dehydrogenase of pig endometrial cells have been used in localization studies with immunogold electron microscopy. The antibodies attach both to a fraction of dehydrogenase-rich cytoplasmic vesicles isolated from homogenates and to vesicles of similar appearance in cells. The vesicles are filled with electron-dense material. Their tagging intensity indicates a high degree of specialization. Endometrial cells from mature animals contain a host of dehydrogenase vesicles, and cells from prepubertal animals only a few. Functional aspects of the novel organelle are discussed. PMID- 8457207 TI - Formation of N-hydroxy-N-arylacetamides from nitroso aromatic compounds by the mammalian pyruvate dehydrogenase complex. AB - Bovine, human and porcine heart mitochondria and isolated porcine heart pyruvate dehydrogenase complex (PDHC) pyruvate-dependently form N-hydroxy-N-arylacetamides from nitroso aromatic compounds, including carcinogenic 4-biphenyl and 2 fluorenyl derivatives. The PDHC-catalysed formation of N-hydroxyacetanilide (N-OH AA) from nitrosobenzene (NOB), through a Ping Pong mechanism, is optimum at pH 6.8 and is accelerated by thiamin pyrophosphate, but is inhibited by thiamin thiazolone pyrophosphate and ATP. Km pyruvate in the reaction is independent of pH over the range tested, whereas KmNOB increases at lower pH, owing to ionization of an active-site functional group of pKa 6.3. The enzymic ionization decreases log (Vmax/KmNOB). Isolated pyruvate dehydrogenase (E1), a constitutive enzyme of PDHC, forms N-OH-AA by itself and has comparable kinetic parameters to those of the PDHC-catalysed N-OH-AA formation. The catalytic efficiency of PDHC in the formation of N-hydroxy-N-arylacylamides, due to the steric limitation of the active site of E1, is lowered both by bulky alkyl groups of alpha-oxo acids and by p-substituents (but not an o-substituent) on nitrosobenzenes. These nitroso compounds serve as electrophiles in the reaction in which the reductive acetylation step is rate-limiting. The reaction mechanism and other factors affecting N-hydroxy-N-arylacylamide formation are discussed. PMID- 8457208 TI - The hyaluronate synthase from a eukaryotic cell line. AB - The hyaluronate synthase complex was identified in plasma membranes from B6 cells. It contained two subunits of molecular masses 52 kDa and 60 kDa which bound the precursor UDP-GlcA in digitonin solution and partitioned into the aqueous phase, together with nascent hyaluronate upon Triton X-114 phase separation. The 52 kDa protein cross-reacted with poly- and monoclonal antibodies raised against the streptococcal hyaluronate synthase and the 60 kDa protein was recognized by monoclonal antibodies raised against a hyaluronate receptor. The 52 kDa protein was purified to homogeneity by affinity chromatography with monoclonal anti-hyaluronate synthase. PMID- 8457209 TI - Separation of native and truncated forms of poliovirus protease 3C produced in Escherichia coli. AB - Poliovirus protease 3C is a cysteine enzyme that is essential for the processing of the viral precursor polyprotein containing structural proteins and enzymes, including the protease itself. We have constructed the plasmid pSD/PV3C which produced protease 3C as inclusion bodies when expressed in Escherichia coli. In addition to the full-length protease, a truncated form was also generated, starting from an internal initiation site (Met-27). The enzyme was renatured by dilution of a 6 M guanidinium chloride solution of the inclusion bodies, and the proteins were precipitated from the diluted solution with ammonium sulphate. By extracting the precipitate with a buffer solution, the full-length enzyme could be completely separated from its N-terminally truncated form. Size-exclusion chromatography of the extracted protease 3C resulted in an active enzyme which appeared homogeneous by SDS/PAGE. For measuring the activity of the protease, a spectrofluorimetric method was devised to monitor the hydrolysis continuously, which is simpler and more precise than the h.p.l.c. technique used previously. PMID- 8457210 TI - Expression and partial characterization of a cathepsin B-like enzyme (Sm31) and a proposed 'haemoglobinase' (Sm32) from Schistosoma mansoni. AB - Schistosoma mansoni protein Sm31 is a cysteine proteinase similar to mammalian lysosomal cathepsin B, proposed to be a key enzyme in schistosome metabolism. Protein Sm32 has been identified as a putative cysteine proteinase termed a 'haemoglobinase'. Since neither Sm31 nor Sm32 have been completely purified, some controversy of the nature of the 'true' digestive enzyme still exists. By incubating a radiolabelled cysteine-proteinase active-site-directed synthetic inhibitor with total S. mansoni proteins, the target of inhibition was Sm31 and not Sm32. The selectivity and irreversibility of inactivation make affinity labelling an invaluable tool for exploring key differences among closely related enzymes and also for studying proteinase activity in a cellular environment. In order to confirm these results, we expressed the complete cDNA sequences of Sm31 and Sm32 in insect cells and analysed the recombinant gene products for proteolytic activities. Cell extracts containing S. mansoni cathepsin B, but not those expressing 'haemoglobinase', were demonstrated to cleave a synthetic substrate benzyloxycarbonyl-arginylarginylaminomethylcoumarin in fluorescence assays. Our findings confirm previous assertions that a cysteine proteinase resembling cathepsin B is the haemoglobinase involved in digestion of host proteins. Thus, the original proposal that Sm32 is a cysteine proteinase has not been verified, and its function remains unknown. PMID- 8457211 TI - The G9a gene in the human major histocompatibility complex encodes a novel protein containing ankyrin-like repeats. AB - The class III region of the human major histocompatibility complex spans approx. 1.1 Mbp on the short arm of chromosome 6 and is known to contain at least 36 genes. The complete nucleotide sequence of a 3.4 kb mRNA from one of these genes, G9a (or BAT8), has been determined from cDNA and genomic DNA clones. The single copy G9a gene encodes a protein product of 1001 amino acids with a predicted molecular mass of 111,518 Da. The C-terminal region (residues 730-999) of the G9a protein has been expressed in Escherichia coli as a fusion protein with the 26 kDa glutathione S-transferase of Schistosoma japonicum (Sj26). The fusion protein has been used to raise antisera which, in Western-blot analysis, cross-react specifically with an intracellular protein of approx. 98 kDa. The function of the G9a protein is unknown. However, comparison of the derived amino acid sequence of G9a with the protein databases has revealed interesting similarities with a number of other proteins. The C-terminal region of G9a is 35% identical with a 149 amino acid segment of the Drosophila trithorax protein. In addition the G9a protein has been shown to contain six contiguous copies of a 33-amino acid repeat. This repeat, originally identified in the Notch protein of Drosophila and known as the cdc10/SW16 or ANK repeat, is also found in a number of other human proteins and may be involved in intracellular protein-protein interactions. PMID- 8457212 TI - Circular dichroism analysis of ligand-induced conformational changes in protein kinase C. Mechanism of translocation of the enzyme from the cytosol to the membranes and its implications. AB - The structural changes following the binding to protein kinase C (PKC) of activators that promote its translocation to lipid environments were studied by far-u.v. c.d. and intrinsic fluorescence measurements of the protein. In the absence of activators, PKC contained 40% alpha-helix, with an average size of 13 amino acids per alpha-helix segment, and 12% beta-structure as deduced from c.d. spectral analysis while fitting a set of model proteins of known structure. Ligands that promote translocation and activation of the enzyme, such as Ca2+ ions and phorbol esters, produced drastic changes in the c.d. spectra which may be interpreted as a reduction in the average number of consecutive amino acids in the alpha-helix. Most of the total alpha-helix structure was conserved and an increase in beta-structure was produced by active phorbol esters. These activators differentially affected the fluorescence of PKC: phorbol esters shifted the emission maximum to the red, whereas Ca2+ produced a marked decrease in the intensity of the fluorescence emission, suggesting in both cases that tryptophan residues were exposed to increased polar environments after binding of the ligands. PMID- 8457213 TI - Clearance from plasma of triacylglycerol and cholesteryl ester after intravenous injection of chylomicron-like lipid emulsions in rats and man. AB - Chylomicrons transport fat and cholesterol via lymphatic vessels from the intestine into the bloodstream. The understanding of the metabolism of chylomicrons in man has been slowed by the difficulty of obtaining lymph chylomicrons for experimental studies. Acceptable methods for the study of chylomicron clearance in man are required, because the metabolism of chylomicrons may be abnormal in diseases such as diabetes mellitus. Metabolism of chylomicrons may also play a role in the development of atherosclerosis. In the present work, lipid emulsions were used as a physical model of chylomicrons. Triacylglycerol rich lipid emulsions labelled with tracer amounts of radioactive triolein and cholesteryl oleate were prepared by sonication and purified by density gradient ultracentrifugation, then injected into unanaesthetized rats and normal human subjects. Plasma radioactivities were measured for 30 min in rats and 90 min in human subjects. Rat lymph chylomicrons were also injected into rats for comparison with the clearance of the lipid emulsions. The plasma clearance data for triacylglycerols and cholesteryl esters were fitted with a kinetic model using the SAAM/CONSAM programs. Multiple studies analysis of the individual studies in each group was used to obtain estimates of the parameter average values and variabilities. The plasma residence times of the lipid labels were obtained from the fitted clearance data. Our results suggest that information about chylomicron metabolism in man can be obtained by analysis of the plasma clearance data following the injection of suitably labelled chylomicron-like lipid emulsions. Our data provide a baseline for comparisons with individuals having abnormalities of lipid metabolism or risk factors for arteriosclerosis. PMID- 8457214 TI - Beta-mannanase of Streptomyces lividans 66: cloning and DNA sequence of the manA gene and characterization of the enzyme. AB - The gene coding for a beta-mannanase was cloned homologously from Streptomyces lividans and its DNA sequence was determined. The fully secreted enzyme was isolated and purified from culture filtrates of the hyperproducing clone S. lividans IAF36 grown in mineral salt media containing galactomannan as the main carbon source. It had a molecular mass of 36 kDa and a specific activity of 876 i.u./mg of protein. Under the assay conditions used, the optimal enzyme activity was obtained at 58 degrees C and a pH of 6.8. The pI was 3.5. The kinetic constants of this mannanase determined with galactomannan as substrate were a Vmax. of 205 i.u./mg of enzyme and a Km of 0.77 mg/ml. Data from SDS/PAGE and Western blotting show that the cloned enzyme was identical to that of the wild type strain. PMID- 8457215 TI - Extracellular-matrix degradation at acid pH. Avian osteoclast acid collagenase isolation and characterization. AB - Osteoclasts degrade bone matrix, which is mainly type I collagen and hydroxyapatite, in an acidic extracellular compartment. Thus we reasoned that osteoclasts must produce an acid collagenase. We purified this enzyme, a 31 kDa protein, from avian osteoclast lysates (in 100 mM acetate/1 mM CHAPS/1 mM dithiothreitol, pH 4.4), fractionated by (NH2)2SO4 precipitation, gelatin affinity, cation exchange, and gel filtration. Fraction activity was measured using diazotized collagen or 3H-labelled cross-linked collagen (decalcified and trypsin-treated metabolically L-[4,5-3H]proline-labelled bone) as substrates. Iodoacetate, leupeptin, antipain, pepstatin and mercurials inhibited collagenolysis by the isolated proteinase; mercurial derivatives could not be re activated by dithiothreitol. Collagen degradation was maximal at pH 4.4; purified proteinase reproduced the collagenolytic activity of cell lysates. The N-terminal amino acid sequence from the isolated protein and its CNBr degradation fragments showed sequence similarity to mammalian cathepsin Bs, and near-identity with avian liver cathepsin B. Peptide substrate specificity of the osteoclastic enzyme resembled those of mammalian cathepsin B and its avian liver counterpart, but degradation of low-molecular-mass substrates by the osteoclastic enzyme was slower, reflecting generally lower kcat. values. Further, kcat/Km varied less between arginine-containing substrates than for previously reported cathepsin Bs, indicating different substrate specificity of the osteoclast enzyme. Polyclonal antibody raised to a 25 kDa fragment of the enzyme recognized a single 31 kDa band in SDS/PAGE of osteoclast lysates blotted to poly(vinylidene difluoride), adsorbed collagenolytic activity of osteoclast lysates, and stained avian osteoclasts in tissue sections. Degenerate sense- and antisense-oligonucleotide primers, predicted from segments of primary amino acid sequence, amplified a 486 bp DNA fragment; this was cloned and sequenced. Of 162 amino acids encoded, 77% are identical with those of human cathepsin B; hybridization identified a 2.4 kb RNA in osteoclast lysates. We conclude that the major avian osteoclast collagenolytic enzyme is a cathepsin B, whose activity varies from other enzymes of its class. PMID- 8457216 TI - Differences in decorin expression by papillary and reticular fibroblasts in vivo and in vitro. AB - Immunostaining of adult human skin shows that the small dermatan sulphate proteoglycan decorin is abundant in the whole dermal layer but absent from the epidermis. In the papillary layer adjacent to the dermal-epidermal border, more decorin was detected than in the reticular layer of the dermis. Expression of decorin mRNA by cells in the papillary dermis could also be shown by in situ hybridization. In contrast, biglycan, another small chondroitin sulphate/dermatan sulphate proteoglycan, is found only at the dermal-epidermal border. Therefore the biosynthesis of these two proteoglycans by papillary and reticular fibroblasts from two different donors was compared in tissue culture. Papillary fibroblasts secrete up to 5.9 times more decorin than reticular fibroblasts, while the amounts of cell-associated decorin in both cell types are similar. By Northern blot analysis as well as by in situ hybridization it was shown that papillary fibroblasts contain more mRNA coding for decorin than do reticular cells. In addition, no mosaic pattern of decorin expression was found in the cultured cells. The expression and synthesis of biglycan compared with decorin was about 10 times lower and did not show any significant differences for the two cells types. The kinetics of secretion and the rate of endocytosis of decorin were similar for both types of fibroblasts. These results were found with fibroblasts between the 9th and 15th passage from a newborn subject as well as from a 78-year-old donor, indicating that the pattern of decorin synthesis is not age-dependent in the range investigated. These results further show that fibroblasts from different layers of the dermis have a specific pattern of synthesis of small chondroitin sulphate/dermatan sulphate proteoglycans, and they also maintain these patterns in cell culture. PMID- 8457217 TI - Effect of insulin on the rates of synthesis and degradation of GLUT1 and GLUT4 glucose transporters in 3T3-L1 adipocytes. AB - The effect of continuous insulin stimulation on the rates of turnover and on the total cellular contents of the glucose-transporter proteins GLUT1 and GLUT4 in 3T3-L1 adipocytes was investigated. Pulse-and-chase studies with [35S]methionine followed by immunoprecipitation of GLUT1 and GLUT4 with isoform-specific antibodies revealed the half-lives of these proteins to be 19 h and 50 h respectively. Inclusion of 100 nM insulin in the chase medium resulted in a decrease in the half-lives of both proteins to about 15.5 h. This effect of insulin was specific for the glucose-transporter proteins, as the average half life of all proteins was found to be 55 h both with and without insulin stimulation. The effect of insulin on the rate of synthesis of the glucose transporters was determined by the rate of incorporation of [35S]methionine. After 24 h of insulin treatment, the rate of synthesis of GLUT1 and GLUT4 were elevated over control levels by 3.5-fold and 2-fold respectively. After 72 h of treatment under the same conditions, the rate of synthesis of GLUT1 remained elevated by 2.5-fold, whereas the GLUT4 synthesis rate was not different from control levels. Western-blot analysis of total cellular membranes revealed a 4.5 fold increase in total cellular GLUT1 content and a 50% decrease in total cellular GLUT4 after 72 h of insulin treatment. These observations suggest that the rates of synthesis and degradation of GLUT1 and GLUT4 in 3T3-L1 adipocytes are regulated independently and that these cells respond to prolonged insulin treatment by altering the metabolism of GLUT1 and GLUT4 proteins in a specific manner. PMID- 8457218 TI - The American College of Rheumatology. Evolution through planning. PMID- 8457219 TI - Evidence suggesting that health education for self-management in patients with chronic arthritis has sustained health benefits while reducing health care costs. AB - OBJECTIVE: To determine the effects of the Arthritis Self-Management Program 4 years after participation in it. METHODS: Valid self-administered instruments were used to measure health status, psychological states, and health service utilization. RESULTS: Pain had declined a mean of 20% and visits to physicians 40%, while physical disability had increased 9%. Comparison groups did not show similar changes. Estimated 4-year savings were $648 per rheumatoid arthritis patient and $189 per osteoarthritis patient. CONCLUSION: Health education in chronic arthritis may add significant and sustained benefits to conventional therapy while reducing costs. PMID- 8457220 TI - The cost-effectiveness of misoprostol for nonsteroidal antiinflammatory drug associated adverse gastrointestinal events. AB - OBJECTIVE: To compare, in a Canadian health care setting, the costs and consequences of 3 strategies of misoprostol prophylaxis for osteoarthritis patients: prophylaxis for all patients taking nonsteroidal antiinflammatory drugs (NSAIDs), for no patients taking NSAIDs, and for only elderly patients (age > or = 60) taking NSAIDs. METHODS: We designed a decision-analysis model which incorporated costs (estimated with ulcer patient profiles and medical records), review, and probabilities (estimated from a companion meta-analysis, selected literature review, and Ontario Ministry of Health Statistics). Effectiveness was defined as the number of episodes of gastric ulceration requiring hospitalization or outpatient management that were averted by each strategy. RESULTS: On average, prophylaxis cost an additional $650 for every additional gastrointestinal event prevented. Prophylaxis for elderly NSAID users was cost saving if the ulcer complication rate in this group exceeds 1.2%, or if either the charges for outpatient ulcer treatment exceed $2,000, or the 3-month price of misoprostol is < or = $90. CONCLUSION: Our results demonstrate that, in this setting, misoprostol prophylaxis may be highly cost effective. PMID- 8457221 TI - Cancer in systemic sclerosis. AB - OBJECTIVE: To determine whether the frequency of cancer is increased among patients with systemic sclerosis (SSc). METHODS: A retrospective chart review of 248 patients who were followed up prospectively was conducted. RESULTS: Cancers developed in 18 patients (7.3%) during 2,001 patient-years at risk. The most frequent types were cancers of the lung (7 patients) and breast (5 patients). Older age at diagnosis of SSc was a significant risk factor for cancer. Lung cancer was associated with the presence of pulmonary fibrosis. The age standardized incidence rate for all cancers (7.9/1,000) was 2.1 times the overall rate in the Ontario population (P < 0.0001). CONCLUSION: The frequency of cancer is increased in patients with SSc. PMID- 8457222 TI - HLA class II alleles and heterogeneity of juvenile rheumatoid arthritis. DRB1*0101 may define a novel subset of the disease. AB - OBJECTIVE: To examine the distribution of HLA class II alleles in clinically distinct juvenile rheumatoid arthritis (JRA) subsets. METHODS: We typed 298 patients and 181 controls for HLA-DRB1, DQA1, DQB1, and DPB1 alleles using polymerase chain reaction and oligonucleotide probe techniques. RESULTS: Each JRA subset was characterized by a distinct distribution of HLA class II alleles. For the persistently pauciarticular and rheumatoid factor-negative polyarticular JRA subsets, certain combinations of DRB1 and DPB1 alleles were characteristic. In patients without antinuclear antibodies and chronic iridocyclitis, there was an increase of DRB1*0101/02 and DQA1*0101. CONCLUSION: Findings of HLA typing support clinical subdivisions of the disease and suggest the existence of a novel DRB1*0101/02 and DQA1*0101 associated disease subset. PMID- 8457223 TI - Linkage studies of HLA and primary Sjogren's syndrome in multicase families. AB - OBJECTIVE: To define the role of HLA-DR phenotype in the expression of primary Sjogren's syndrome (SS). METHODS: A family study of Caucasian probands with definite primary SS was conducted. Relatives with features of primary SS were classified according to the Fox criteria. Several types of linkage analysis between primary SS and HLA haplotype (HLA-A, B, and DR) were performed. RESULTS: A trend toward haplotype sharing between affected siblings was evident for definite/probable primary SS when analyzed by the Green and Woodrow method. This reached statistical significance when data from other published family studies were included. LOD scores and analyses using the Penrose method showed little evidence of linkage. CONCLUSION: In view of the strong association with HLA-DR3, these results suggest that the HLA-DR3 allele is an important susceptibility factor for expression of primary SS in Caucasians. The apparent haplotype sharing may be a consequence of this association. The potential influence of other genetic factors (major histocompatibility complex [MHC] and non-MHC) is discussed. PMID- 8457225 TI - Enhanced chondrocyte destruction by lymphokine-activated killer cells. Possible role in rheumatoid arthritis. AB - OBJECTIVE: The lysis of chondrocytes, the parenchymal cells of cartilage, by lymphocytes may provide a potent mechanism by which the immune system participates in sustaining joint damage in rheumatoid arthritis (RA). We studied the capability of lymphocytes from healthy individuals and patients with arthritis to lyse chondrocytes. METHODS: Peripheral blood mononuclear cells (PMBC) were tested for their ability to lyse chondrocytes in a 51Cr-release assay. Enhancement of the chondrolytic activity was determined by preincubating the cells with T cell growth factor (TCGF) or recombinant interleukin-2 (rIL-2) before cytotoxic testing. RESULTS: PBMC from healthy individuals possessed a low ability to lyse chondrocytes, whereas cells from the synovial fluid of patients with RA displayed higher chondrolytic activity. In RA, modulating factors must come into play because not all synovial fluid sample cells showed high chondrolytic activity and cells from synovial tissue had little or no lytic action on chondrocytes. Chondrolytic activities of cells from all sources, including PBMC from healthy subjects and patients with arthritis and cells isolated from synovial fluid or from the synovial tissue of RA patients, were greatly increased by incubating the cells with TCGF or rIL-2. In contrast, treatment of chondrocytes with interferon-gamma, which enhances major histocompatibility complex gene expression, decreased the susceptibility of chondrocytes to lysis. CONCLUSION: These observations suggest a mechanism for joint damage in which the destruction of chondrocytes by lymphocytes is controlled by cytokines released during the inflammatory process in arthritic diseases. PMID- 8457224 TI - Levels of circulating tumor necrosis factor alpha and interleukin-6 in patients with rheumatoid arthritis. Relationship to serum levels of hyaluronan and antigenic keratan sulfate. AB - OBJECTIVE: To measure serum levels of tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) in patients with rheumatoid arthritis (RA) and age-matched control subjects and to study how these correlate with serum levels of hyaluronan (HA) and antigenic keratan sulfate (KS) and other biochemical as well as clinical indicators of disease activity. METHODS: Immunoassays were used to measure levels of TNF alpha, IL-6, HA, and antigenic KS in the serum of 35 patients with RA and a group of age- and sex-matched control subjects. Clinical disease activity in the RA group was assessed using the Lansbury index. Drug intake was recorded and the erythrocyte sedimentation rate, and levels of fibrinogen, creatinine, bilirubin, alkaline phosphatase, lactate dehydrogenase, and aminotransferase were measured. RESULTS: Serum levels of TNF alpha, IL-6, and HA were significantly higher in the RA population than in the control group. In patients with RA, serum levels of HA correlated positively with serum levels of TNF alpha and with clinical joint scores, but only weakly with other laboratory parameters of inflammation. Serum levels of antigenic KS correlated negatively with levels of circulating TNF alpha, but much more weakly with other clinical and biochemical parameters of disease activity. CONCLUSION: These in vivo data support in vitro studies which have shown that TNF alpha is a potent stimulator of HA synthesis by synovial lining cells. The results strengthen the contention that serum HA may be a unique marker of synovial involvement and inflammation, rather than of only inflammation, in RA. PMID- 8457226 TI - Suppression of human cartilage proteoglycan synthesis by rheumatoid synovial fluid mononuclear cells activated with mycobacterial 60-kd heat-shock protein. AB - OBJECTIVE: To examine whether T cell reactivity toward heat-shock proteins (HSP) contributes to cartilage destruction in rheumatoid arthritis (RA). METHODS: An in vitro system was used, in which human cartilage explants were cocultured with hsp60-activated synovial fluid mononuclear cells (SFMC) from patients with RA, and proteoglycan (PG) synthesis was measured. RESULTS: The hsp60-activated SFMC suppressed cartilage PG synthesis. This effect was dependent on the production of interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha). CONCLUSION: Mycobacterial 60-kd heat-shock protein can activate rheumatoid SFMC to suppress human cartilage PG synthesis. This suppression is mediated by IL-1 and TNF alpha. PMID- 8457227 TI - Different manifestations of the antiphospholipid antibody syndrome in a family with systemic lupus erythematosus. AB - OBJECTIVE: Familial associations of the antiphospholipid antibody syndrome (APS) offer the opportunity to study genetic mechanisms of autoantibody production and disease, but are unusual. We identified a family, including identical twins and their mother, in which all members had systemic lupus erythematosus (SLE) and presented with different manifestations of the APS. METHODS: Review of case histories and clinical laboratory results, antiphospholipid antibody (aPL) studies, complement C4 protein and gene analysis, and HLA typing of family members were performed. RESULTS: Each of the 3 family members presented with a different clinical association of the APS. These various clinical presentations were closely temporally related. No particular aPL activity could be separated out that would account for the different manifestations, although the twin with thrombocytopenia and livedo reticularis had a strikingly high IgM anticardiolipin antibody level. C4A or C4B deficiencies could not be implicated in the autoimmune process. However, the mother and the twins shared the HLA haplotype that included the class II antigens DR4, DRw53, and DQw7, which has previously been associated with aPL production. CONCLUSION: This family study emphasizes the different clinical associations of aPL production in SLE. In addition to genetic influences that appear to include HLA class II antigens, the clinical presentations also suggest an environmental trigger. PMID- 8457228 TI - Evaluation of the European Spondylarthropathy Study Group preliminary classification criteria in Alaskan Eskimo populations. AB - OBJECTIVE: To evaluate the preliminary classification criteria proposed by the European Spondylarthropathy Study Group (ESSG) in Alaskan Eskimo populations. METHODS: We examined, interviewed, and reviewed the records of 104 Eskimo patients with spondylarthropathy and 75 with other rheumatic disorders, and evaluated them according to the proposed criteria. RESULTS: We found an overall sensitivity of 88.5% and a specificity of 89.3%, which is similar to the reported values in European populations. CONCLUSION: The ESSG criteria performed well in a population very different from that in which they were developed, and deserve further evaluation as a much-needed and useful epidemiologic tool. PMID- 8457229 TI - Nucleosome-specific antibody from an autoimmune MRL/Mp-lpr/lpr mouse. AB - OBJECTIVE: To characterize the binding properties and variable-region sequences of LG4-1, a monoclonal antibody from an autoimmune MRL/Mp-lpr/lpr mouse that reacts specifically with nucleosome core particles and represents a new antinuclear antibody specificity. METHODS: The reactivity of the antibody against various nuclear substrates was determined using an enzymatic immunoassay, and the variable-region genes were sequenced from messenger RNA, using the dideoxy chain termination method. RESULTS: LG4-1 was found to react with nucleosome core particles but not with individual histones and DNA, or with various histone histone and histone-DNA complexes. It was demonstrated that this antibody is encoded by a combination of variable-region genes and gene segments that have undergone few somatic mutations. CONCLUSION: The nucleosome core particle expresses a unique conformational autoepitope(s) resulting from the ordered association of histones and DNA. PMID- 8457230 TI - VH family utilization by IgG anti-DNA-secreting lymphocytes derived from autoimmune MRL-lpr/lpr mice. AB - OBJECTIVE: To evaluate the heterogeneity of the IgG anti-DNA autoantibody response of MRL/lpr mice. METHODS: B cell clones were grown on nitrocellulose membranes. Those producing IgG anti-DNA antibodies were identified by a modified enzyme-linked immunospot assay, and their utilization of IgVH genes was determined by hybridization. RESULTS: Four hundred sixty-eight IgG anti-DNA secreting colonies were derived from 9 autoimmune MRL/lpr mice. Individual VH families contributed to anti-DNA production at a frequency roughly proportional to their representation in the expressed repertoire (except for the more frequent use of VH 7183 and less frequent use of VH 36-60). In individual mice, anti-DNA antibodies were encoded by 2-5 different IgVH families, with no single family constituting more than 27-65% of any animal's anti-DNA response. CONCLUSION: The IgG anti-DNA response of individual MRL/lpr mice is oligoclonal. PMID- 8457231 TI - Enlargement of the hands and feet in a chronic smoker. PMID- 8457232 TI - Radiologic vignette. The radiographic findings are typical of herniation pit of the femoral neck. PMID- 8457233 TI - Use of gloves for rheumatology procedures. PMID- 8457234 TI - Reproductive toxicity studies of the antihypertensive agent felodipine in the rat. AB - Felodipine (4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridine dicarboxylic acid 5-ethyl 3-methyl ester, CAS 72509-76-3), a vascular selective dihydropyridine calcium antagonist, was tested in three different reproduction studies in the rat. In fertility, teratology and peri-postnatal studies Sprague Dawley rats were dosed by gavage with 10, 25 and 70 mumol/kg (fertility and teratology studies) or 3, 10 and 30 mumol/kg (peri-postnatal study). There were no increased incidences of external, visceral or skeletal malformations in the teratology study in groups treated with felodipine during organogenesis, compared with the control group. In the fertility and peri-postnatal studies, prolonged parturition and increased incidences of stillborn fetuses and postnatal death were observed in groups given 10 mumol/kg or more, but not at 3 mumol/kg. Similar to the findings in this study, nifedipine, nitrendipine, nicardipine, diltiazem and isradipine have all been reported to induce increased incidences of perinatal death in offsprings in peri-postnatal studies. Thus, the increased incidences of perinatal death (most likely secondary to inhibition of the uterine activity) seems to be a class effect common to all calcium antagonists. PMID- 8457235 TI - Platelet anti-aggregant and rheological properties of piracetam. A pharmacodynamic study in normal subjects. AB - The random administration of four different single oral doses of piracetam (Nootropil, CAS 7491-74-9)--1.6 g, 3.2 g, 4.8 g and 9.6 g--at fixed intervals of 2 weeks to 5 healthy subjects has confirmed and explicited its platelet anti aggregant and rheological properties after doses of 4.8 g and 9.6 g. The effect on platelet aggregation occurs through inhibition of thromboxane synthetase or anti-thromboxane A2 activity together with a reduction in the plasma level of von Willebrand's factor (F.VIIIR:vW). The rheological effect is related to the action of piracetam on cell membrane deformability (red cells, white cells and platelets) and to its simultaneous effect in reducing by 30-40% plasma levels of fibrinogen and von Willebrand's factor. In addition, it exerts a direct stimulant effect on prostacyclin synthesis in healthy endothelium. These effects are greatest between 1 and 4 h after dosage, and then diminish progressively to disappear between 8 and 12 h after administration. This explains the need to divide the total daily dose into 3 intakes at 8-hourly intervals. This study confirms the presence of four sites of action of piracetam: the vessel wall, platelets, plasma and cell membranes (RBC, WBC), which provide the basis for the potentially important antithrombotic activity of piracetam. PMID- 8457236 TI - Effects of a dried garlic preparation on fibrinolysis and platelet aggregation in healthy subjects. AB - The acute and chronic effects of a preparation of dried garlic powder (Sapec) in a total daily dose of 900 mg on fibrinolysis and platelet aggregation have been evaluated in a randomized, double-blind, placebo controlled cross-over study of 12 healthy subjects. Total euglobulin fibrinolytic activity and t-PA (tissue plasminogen activator) activity were significantly higher 4 and 6 h after garlic and placebo ingestion, and no differences were recorded between treatments. After 14 days of treatment, t-PA activity was significantly higher after garlic, with inter-treatment significance. No significant changes in PAI (Plasminogen Activator Inhibitor) activity and fibrinogen levels were recorded. Platelet aggregation induced by adenosine diphosphate and collagen, and especially beta thromboglobulin (beta-TG) release after collagen stimulation were significantly inhibited 2 and 4 h after garlic ingestion; platelet aggregation values were also significantly lower after 7 and 14 days of garlic treatment. No significant changes were found in adenosine triphosphate release and serum TXB2 levels after acute garlic administration. PMID- 8457237 TI - Activity of topically applied methylprednisolone aceponate in relation to other topical glucocorticosteroids in healthy volunteers. AB - Topical glucocorticosteroids are useful in the treatment of various skin diseases. Although there are already many corticosteroids available, there is still need for highly potent and well tolerated ones. The anti-inflammatory activity of methylprednisolone aceponate (MPA, CAS 86401-95-8) has been investigated in 165 healthy volunteers of either sex. UV-B irradiation or cellophane tape stripping has served to produce erythema. First, the dose response relationship of MPA ointment (0.01%, 0.05%, 0.1% and 0.5%) has been evaluated. MPA effects have been related to those of the vehicle and difluocortolone 21-valerate 0.1% (DFV) ointment. Then the activity of 0.1% MPA (cream, ointment and fatty ointment) has been related to those of the respective vehicles as well as commercially available preparations of five corticosteroids: betamethasone 17,21-dipropionate 0.64% (BDP), betamethasone 17-valerate 0.1% (BV), clobetasol 17-propionate 0.05% (CP), hydrocortisone 17-butyrate 0.1% (HCB), prednicarbate 0.25% (P). In each experiment, MPA activity significantly exceeded that of the respective vehicle (p < or = 0.05). MPA 0.01-0.5% ointment exhibited strong anti-inflammatory activity, at least corresponding to that of 0.1% DFV ointment. A dose-dependent activity could only be observed in the UV-B-erythema test using 3 fold MED (minimal erythema doses) for irradiation, a test model differentiating strong corticosteroids. The comparison of 0.1% MPA formulations with respective reference preparations showed the following results: On stripped skin no significant differences could be detected which is demonstrated in the example of cream formulations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457238 TI - Pharmacokinetic study of 4'-acetamidophenyl-2-(5'-p-toluyl-1' methylpyrrole)acetate in the rat. AB - A pharmacokinetic study has been performed on a new non-steroidal anti inflammatory drug, AU-8001 (4'-acetamidophenyl-2-(5'-p-toluyl-1' methylpyrrole)acetate, CAS 82239-77-8) in the rat, following intravenous (10 mg/kg) and oral (50 mg/kg) administrations. The new molecule constitutes a prodrug of paracetamol and tolmetin. Compartmental and non-compartmental treatment of experimental data lead to the same conclusions. After intravenous administration, the rapid hydrolysis of the ester function of the molecule causes a short transit of the prodrug in the organism and the rapid attainment of maximum plasmatic levels of metabolites. After oral administration, the prodrug shows flip-flop behaviour in which the absorption constant rate is the limiting factor and is responsible for the slow bioconversion of the substance. The bioavailability of the prodrug is incomplete and, according to the urinary excretion data, a fraction of the dose reaches the blood stream in the form of metabolites. AU-8001, however, in spite of its limited bioavailability, is a model prodrug which could be used to prolong the activity of the original drugs. PMID- 8457239 TI - Nimesulide in the treatment of hyperpyrexia in the aged. Double-blind comparison with paracetamol. AB - The efficacy and safety of nimesulide (Aulin, CAS 51803-78-2) in a new pharmaceutical suppository form (200 mg) were assessed in a double-blind study versus paracetamol suppositories (500 mg). The study was conducted in a sample of aged in-patients suffering from viral or bacterial infections of upper and lower respiratory tract with fever. Thirty-nine patients were randomly assigned to treatment with nimesulide or paracetamol (18 nimesulide, 21 paracetamol). Both drugs, administered t.i.d. for 2 consecutive days followed by observation without therapy on the 3rd day, showed an adequate control of hyperpyrexia with significant reduction of body temperature from baseline. Tolerability was good for both drugs. Only one patient of the nimesulide group could not complete the study because of an adverse reaction consisting in cutaneous erythema with itching that regressed spontaneously. It is concluded that nimesulide is as active and safe as paracetamol in treating hyperpyrexia of the aged. PMID- 8457240 TI - Anthelmintic activity of pyrazinothiadiazine dioxide derivatives. AB - In a search for new anthelmintic compounds, some pyrazinothiadiazine dioxide derivatives were synthesized. Their anthelmintic activity was tested against larva and preadult stages of Trichinella spiralis. The mode of action and acute toxicity of these compounds were investigated. Structure-activity relationships are discussed. PMID- 8457241 TI - Survey on spontaneous systemic amyloidosis in aging mice. AB - The incidence of systemic amyloidosis in CD-1 mice (Charles River, caesarian derived) obtained from long term studies over more than a 15-year period is reported. The survey included samples of visceral organs, peripheral and central nervous tissues, bone and bone marrow. The total incidence in all mice of this survey did not show any clear evidence of a difference between males and females. Amyloidosis deposits were mainly seen in the stomach (glandular), heart, small intestines, kidney, liver, spleen, thyroid, parathyroid, adrenals, salivary glands and ovaries, but not in the brain, spinal cord, bone or bone marrow. The survey showed that amyloidosis in CD-1 mice was spontaneous, systemic and it is age-related. Amyloid deposition was extracellular and it stained positively with Congo Red and also stained positively with Oil Red O and Alcian blue. In general, amyloidosis in CD-1 mice, was higher in comparison with B6C3F (cross between C57BL/C6 NCRLB and C3H/HEN NCRLB, (bred by Charles River), CFLP strain (hysterectomy derived strain of Swiss origin) and MAGF: TIF (SPF). This survey also showed that spontaneous systemic amyloidosis in CD-1 mice, was one of the major factors contributory to death in aging CD-1 mice. PMID- 8457242 TI - Increasing DNase I activity after exposure of isolated DNA to halothane. AB - DNA was exposed to halothane (CAS 151-67-7) in a cell-free system. After exposure the DNA was used as substrate for DNase I from bovine pancreas. The DNase I activity increased after halothane exposure of the substrate depending on time and doses. Drugs are able to influence the DNA conformation. Conformational changes in the DNA can enhance the DNase I cleavage rate. Therefore, it is possible that halothane exposure induces changes in DNA conformation demonstrable by an increased DNase I activity. The results suggest a mechanism by which halothane may contribute to chromosomal defects and disturbances of DNA metabolism in cells. PMID- 8457243 TI - Cardioprotective actions of garlic (Allium sativum). AB - The influence of an intake of garlic powder (1%--corresponding to Kwai/Sapec- added to a standard chow for a 10-week period) on the susceptibility to ventricular arrhythmias under ischemia and reperfusion was investigated in the isolated rat heart (Langendorff preparation) perfused with a modified Krebs Henseleit solution. The incidence of ventricular tachycardia (VT) and fibrillation (VF) after ligation of the descending branch of the left coronary artery (LAD) (20 min) was significantly reduced in the garlic group as compared to untreated controls (VT: 0% vs. 35.5%; VF: 50% vs. 88%). The size of the ischemic zone was significantly smaller (31.7% vs. 40.9% of total heart tissue). The reperfusion experiments (5 min after 10 min ischemia) revealed similar results (VT: 50% vs. 100%; VF: 30% vs. 90%). The time until occurrence of extrasystoles and VT or VF was prolonged in most cases, and the duration of arrhythmias was abbreviated. No significant alterations in cardiac membrane fatty acid composition could be found. Inhibition of cyclooxygenase by acetylsalicylic acid (ASA) caused a moderate increase in arrhythmias and ischemic zone in the garlic group as well as in untreated controls under the conditions of the present experiments. Thus, it seems that the prostaglandin system does not play a predominant role in the cardioprotective action of garlic. The significance of free radical scavenging activity of garlic for its antiarrhythmic effects has to be established. PMID- 8457244 TI - Modified forms of low density lipoprotein and atherosclerosis. AB - Modified forms of low density lipoprotein (LDL) are associated with increased atherogenicity. Modified LDL, in comparison with native LDL, demonstrates enhanced cellular uptake by macrophages, foam cell formation and also causes the secretion of cytokines and growth factors from arterial wall cells. Non-enzymatic modifications of LDL (proteoglycans, glycosylation, immune complexes) and enzymatic modifications (lipases, oxygenases) were shown to affect the physicochemical (size, charge) as well as the biological (cellular uptake, secretion) properties of the lipoprotein. Of special interest is the oxidative modification of LDL which was demonstrated to occur in vivo. The mechanism of this process involves cellular lipid peroxidation and requires the binding of LDL to its receptor on macrophages. Some of the modifications can render the LDL more susceptible to other types of modifications (lipid modifications, aggregation, oxidation). As atherosclerosis is a multifactorial disease and since lipases and oxygenases exist in cells of the arterial wall, several forms of modified LDL may exist in vivo. These modifications can occur either in parallel or along different stages of atherogenesis. Inhibition of such LDL modifications may arrest the development of the atherosclerotic lesion. PMID- 8457245 TI - Antibodies to cytoskeletal proteins in sera of patients with angiographically assessed coronary artery disease. AB - Circulating autoantibodies to various components of the arterial wall have been reported in atherosclerosis. To examine the occurrence of autoantibodies to cytoskeletal proteins in coronary artery disease (CAD) we studied 56 patients with angiographically demonstrable CAD and compared them with 37 controls without CAD. Enzyme-linked immunosorbent assay (ELISA) was used to analyze the serum samples. In coronary patients, antibody absorbance values at least two standard deviations above the mean for the controls were considered positive. The following numbers of positive antibody absorbances were found in the group of 56 patients: actin IgG, 6 (10.7%); cytokeratin-18 IgG, 3 (5.4%), IgA, 2 (3.6%); myosin IgA, 11 (19.6%); desmin IgG, 13 (23.2%), IgM, 3 (5.4%); vimentin IgG, 2 (3.6%), IgM, 7 (12.5%), IgA, 6 (10.7%). The specificity of desmin IgG was tested with Western blotting against extracts of human internal mammary artery. The positive antibody absorbances to one or several cytoskeletal proteins in the patients were not found to correlate with the clinical symptoms of CAD. Our results suggest an association between autoantibodies to cytoskeletal proteins, particularly to those for desmin, with angiographically assessable CAD. PMID- 8457246 TI - In vivo oxidised cholesterol in atherosclerosis. PMID- 8457247 TI - Toxicity of oxidised low density lipoprotein towards mouse peritoneal macrophages in vitro. AB - The addition of cupric sulphate-oxidised low density lipoprotein (oxLDL) to mouse peritoneal macrophage (MPM) cultures caused toxicity towards the cells, measured by tritiated adenine release. The degree of toxicity increased with increasing concentrations of oxLDL up to 18 h incubation with MPM, after which the toxicity appeared to be independent of the concentration of oxLDL used. Toxicity was significantly reduced when vitamin E in the form of D,L-alpha-tocopherol was added to the LDL before the artificial oxidation, but vitamin E had no effect on the toxicity when added alongside the oxLDL in the culture medium. However, if the MPM were pre-incubated for 24 h with 80 microM vitamin E, there was a significant reduction in the level of toxicity up to 6 h in culture with oxLDL. There was a strong correlation (r = 0.81) between the degree of oxidation of the LDL, measured as thiobarbituric-reactive substances, and the corresponding toxicity. This indicated that the more oxidised the LDL was, the more toxic it was to the macrophages. Native LDL also led to toxicity, but only after a time lag of 20 h. Again, this toxicity was decreased by pre-incubation of the MPM with vitamin E, but not by addition of vitamin E at the same time as LDL. The findings suggest that oxLDL is capable of contributing to the onset of necrosis during atherogenesis and that the oxidative capacity of the macrophage foam cells themselves might contribute to the process. PMID- 8457248 TI - Increased transfer of cholesteryl esters from high density lipoproteins to low density and very low density lipoproteins in patients with angiographic evidence of coronary artery disease. AB - Cholesterol esterification, transfer of cholesteryl esters from high density lipoproteins to very low density and low density lipoproteins (VLDL/LDL) and the composition of lipoproteins isolated by density gradient ultracentrifugation have been investigated in 18 men with angiographic evidence of severe coronary artery disease and in 27 healthy men without coronary artery disease. Patients had significantly higher serum cholesterol (P < 0.001), serum triglycerides (P < 0.02) and lower high density lipoprotein cholesterol (HDL) (P < 0.04) compared with healthy men. The transfer of cholesteryl ester from HDL to VLDL and LDL was 27.8 +/- 12.2 nmol/ml per h (mean +/- S.D.) in patients and was significantly higher than the value of 17.8 +/- 6.5 nmol/ml per h obtained in healthy men (P < 0.003) or 17.1 +/- 7.6 nmol/ml per h) in 16 controls (P < 0.03) with similar serum cholesterol and triglyceride concentrations. Lipoprotein protein concentrations were significantly higher in LDL (P < 0.05) and small VLDL (P < 0.01) in patients. In addition, patient LDL and large VLDL contained more free cholesterol than matched controls (P < 0.01, P < 0.05, respectively). This was reflected in the increased free cholesterol/phospholipid ratio (a measure of lipoprotein surface composition) in LDL (P < 0.002). These findings indicate that patients with established coronary artery disease have increased transfer of cholesteryl ester from HDL to VLDL and LDL, which is independent of serum triglyceride concentrations. This increased transfer of cholesteryl ester may be a result of the increased free cholesterol content of very low density lipoproteins. PMID- 8457249 TI - Composition of human low density lipoprotein: effects of postprandial triglyceride-rich lipoproteins, lipoprotein lipase, hepatic lipase and cholesteryl ester transfer protein. AB - A preponderance of small, dense low density lipoprotein (LDL) particles has been linked to increased risk of myocardial infarction, and a dense and protein-rich LDL has proved to be a characteristic of patients with manifest coronary heart disease (CHD). The present study focused on metabolic determinants of the LDL subfraction distribution with the emphasis placed on alimentary lipaemia. The relations of plasma levels and composition of light (1.019 < d < 1.040 kg/l) and dense (1.040 < d < 1.063 kg/l) LDL subfractions to postprandial triglyceride-rich lipoproteins (TGRL), postheparin plasma lipase activities and the activity of cholesteryl ester transfer protein (CETP) were studied in 32 men with angiographically ascertained premature coronary atherosclerosis (age 48.8 +/- 3.2 years) and in 10 age matched healthy control men. LDL subfractions were separated by equilibrium density gradient ultracentrifugation of fasting plasma drawn before participants were subjected to an oral fat tolerance test of a mixed meal type. The response of TGRL to the oral fat load was determined by measuring plasma triglycerides, and the apolipoprotein (apo) B-48 and apo B-100 content of Sf 60-400 and Sf 20-60 lipoprotein fractions. At a second visit plasma samples were taken for determination of postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities and for measurement of CETP activity. Hypertriglyceridaemic patients had a preponderance of dense LDL particles compared with normotriglyceridaemic patients and controls. The magnitude of the response of TGRL to the oral fat load showed a positive association with the dense LDL apo B concentration (r = 0.32-0.52, P < 0.05), whereas the LPL activity correlated positively with the free (r = 0.50, P < 0.001) and esterified cholesterol (r = 0.45, P < 0.01) and apo B (r = 0.42, P < 0.01) content of the light LDL fraction. The HL activity was found to be inversely associated with the plasma level of light LDL triglycerides (r = -0.38, P < 0.05). In contrast, no relations were noted between CETP activity and plasma concentrations of LDL constituents. Multiple stepwise linear regression analysis with the proportion of total LDL apo B contained in the dense LDL subfraction (% dense LDL apo B) used as the dependent variable indicated that the combined effect of LPL activity and postprandial plasma levels of TGRL (areas under the curve for plasma triglycerides or Sf 60-400 apo B-48) accounted for around 50% of the variability in the distribution of LDL particles between light and dense subfractions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8457250 TI - Influence of specific mutations at the LDL-receptor gene locus on the response to simvastatin therapy in Afrikaner patients with heterozygous familial hypercholesterolaemia. AB - Simvastatin, an inhibitor of HMG CoA reductase, lowers the plasma total cholesterol and LDL-cholesterol concentration in familial hypercholesterolemic patients. The efficacy of the drug shows considerable inter-individual variation, however. In this study we have assessed the influence of certain LDL-receptor gene mutations on this variation. A group of 20 male and female heterozygotic familial hypercholesterolemic patients, all Afrikaners and each bearing one of two different LDL receptor gene mutations, FH Afrikaner-1 (FH1) and FH Afrikaner 2 (FH2), was treated with simvastatin (40 mg once daily) for 18 months. The average reduction in total plasma cholesterol was 35.3% in the case of the FH2 men but only 23.2% in that of the FH1 men (P = 0.005); the reduction in LDL cholesterol concentrations was also greater in the FH2 group (39% as opposed to 27.1%, P = 0.02). The better response of the FH2 group was also evident when men and women were considered together. Female FH1 patients responded better to simvastatin treatment, however, than did males with the same gene defect. Mutations at the LDL-receptor locus may thus play a significant role in the variable efficacy of the drug. The particular mutations in the males of this group may have contributed up to 35% of the variance in total cholesterol response and 29% of the variance in LDL-cholesterol response to simvastatin treatment. PMID- 8457251 TI - Lipoprotein(a) in patients with carotid atherosclerosis and ischemic cerebrovascular disorders. AB - The aim of this study was to evaluate the role of lipoprotein(a) in the carotid atherosclerosis and ischemic cerebrovascular disorders. Four groups of subjects were included: 49 patients with transient ischemic attacks, 61 with acute cerebral infarction, 48 with asymptomatic carotid atherosclerosis and a group of 50 healthy subjects. Lipoprotein(a) serum concentration and its correlation with various clinical parameters was analysed. The results revealed a significant difference between lipoprotein(a) serum levels in patients and healthy subjects and positive correlation between lipoprotein(a) serum levels and the degree of carotid atherosclerosis. Moreover, some other correlations are found and discussed. It was concluded that lipoprotein(a) is involved in the pathogenesis of carotid atherosclerosis, but it is not associated with the development of ischemic cerebrovascular disorders. PMID- 8457253 TI - Influence of age and menopause on serum lipids and lipoproteins in healthy women. AB - Sex hormone deficiency is associated with increased coronary heart disease (CHD) risk in women. We measured fasting serum lipids and lipoprotein concentrations in a group of 542 healthy non-obese pre- and postmenopausal women (aged 18-70 years). Ageing was associated with increased concentrations of total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein subfraction 3 (HDL3) cholesterol and triglycerides, and decreased concentrations of high density lipoprotein subfraction 2 (HDL2) cholesterol. Body mass index (BMI) was related positively to concentrations of total and LDL cholesterol. Postmenopausal women had significantly higher concentrations of total cholesterol (P < 0.001), triglycerides (P < 0.005), LDL cholesterol (P < 0.001) and high density lipoprotein subfraction 3 (HDL3) cholesterol (P < 0.001), whilst those of HDL and HDL2 cholesterol were significantly lower (P < 0.001). These differences were independent of age, BMI and other potential confounding variables. We conclude that the menopause is associated with potentially adverse changes in lipids and lipoproteins, independent of any effects of ageing. These changes may in part explain the increased incidence of coronary heart disease seen in postmenopausal women. PMID- 8457252 TI - Lipopolysaccharide stimulation of RAW 264.7 macrophages induces lipid accumulation and foam cell formation. AB - A role for immune and inflammatory processes in the induction of atherosclerotic lesions is emerging. These studies were undertaken to determine whether activation by lipopolysaccharide (LPS) enhances the ability of macrophages to become foam cells. Since LPS activation inhibits scavenger receptor activity, we studied the ability of LPS-activated RAW 264.7 macrophages to accumulate lipid from a variety of lipid particles that are not ligands for the scavenger receptor. Macrophages activated by LPS, in the absence of lipid particles, accumulated triglyceride, but not cholesterol ester (CE). The addition of Soyacal, a triglyceride-rich particle, further enhanced this LPS-stimulated triglyceride accumulation. LPS activation similarly enhanced CE accumulation almost 3-fold from two CE-rich lipoproteins, beta VLDL and LDL, as compared with controls. The unstimulated control cells only accumulated significant CE from beta VLDL and not LDL. LPS-enhanced lipid accumulation was dependent on LPS dose and began after 8-12 h of incubation. LPS increased the degradation of 125I labelled LDL and the cell-associated 125I-labelled LDL at 37 degrees C by 1.8 fold. Degradation remained saturable, consistent with a receptor-mediated process. Antioxidants did not inhibit LPS-induced CE accumulation from LDL. Thus, activation of RAW 264.7 macrophages enhanced their ability to accumulate lipid from a variety of lipid particles and to become foam cells. These data suggest a potential role for infections, and LPS in particular, in atherogenesis. PMID- 8457254 TI - Red cell filterability in cigarette smokers and its relations to cardiac hypertrophy. AB - The relationship among daily cigarette consumption, washed and non-washed RBC filterability time (FT) as an indicator of erythrocyte deformability and echocardiographic left ventricular mass (LVM) were examined in 25 clinically healthy smokers and in 25 non-smoking controls matched for sex and age. FT of non washed RBC was significantly higher in smokers than in non-smokers (25.2 +/- 3.6 vs. 16.8 +/- 2.2 min, P < 0.001). A highly significant linear correlation between number of cigarette consumption and FT was found. These differences were not observed when RBC were washed three times with isotonic saline. LVM was significantly greater in smokers (85.5 +/- 13.4 g/m2) than in controls (61.8 +/- 6.7 g/m2, P < 0.001). A linear correlation between daily cigarette consumption and LVM was observed. A positive relationship between LVM and FT of non-washed RBC was also found. These results demonstrated that LVM is significantly elevated in smokers and is linearly correlated with both cigarette consumption and RBC filtratibility. The increased deformability found in smokers may be a determinant to the cardiac hypertrophy. The association of both elevated LVM and rheological impairment may indicate unfavourable prognosis. PMID- 8457255 TI - Structural properties and partial protein sequence analysis of the major dermatan sulfate proteoglycan of pigeon aorta. AB - Dermatan sulfate proteoglycans (DSPG) were extracted from intima-media of grossly normal aortic tissue of White Carneau pigeons and were purified by ion exchange chromatography on DEAE-Sephacel followed by size exclusion chromatography on Sepharose CL-4B. The major aortic DSPG had an average size of 310 kDa. The core protein resulting from treatment of the PG with chondroitinase ABC: (1) was found to be approximately 48 kDa by SDS-polyacrylamide gel electrophoresis; (2) was recognized by monoclonal antibody (Mab) 2-B-6 but not by Mab 3-B-3 on Western blots, indicating the presence of delta Di-4S and absence of delta Di-6S; (3) was glycosylated with Asn-linked oligosaccharides; (4) contained a high content of Asx, Glx and Leu, similar to that found for core proteins of this size from other tissues and species and (5) contained an N-terminal sequence (Asp-Glu-Gly-Xaa-Ala Asp-Met-Pro-Pro-Xaa-Asp-Asp-Pro-Val- Ile-(ile)-Gly-Phe-), which was similar to sequences of DSPG core proteins previously described as 'decorin' and distinct from DSPG described as 'biglycan'. The results suggest that the major DSPG of aorta can be classified as a decorin molecule. The overall size of the DSPG in aorta was larger than decorin molecules described in non-arterial tissues of other species. Evidence is presented to conclude the larger size results from more than one dermatan sulfate-glycosaminoglycan chain. PMID- 8457256 TI - Effects of fenofibrate on angiographically examined coronary atherosclerosis and left ventricular function in hypercholesterolemic patients. AB - Within the framework of a prospective lipid-lowering intervention study 44 patients were treated over a period of 3 years with a lipid-lowering diet and 200 400 mg fenofibrate daily. The intervention led to statistically significant decreases in total cholesterol (Chol), low density lipoprotein cholesterol (LDL Chol) and triglycerides levels, and to a significant increase in high density lipoprotein cholesterol (HDL-Chol) levels. Despite intervention, in 8 patients the HDL-Chol levels decreased by up to 20 mg/dl, where these were mainly patients with high initial values. Likewise, the triglycerides of 4 patients whose initial levels were relatively low increased (up to 49 mg/dl) and the LDL-Chol levels of 8 patients whose initial levels were also low increased (up to 49 mg/dl). Only minor success was achieved through the 6-week diet, but this was still slightly significant for Chol and LDL-Chol levels. A total of 21 patients underwent repeat angiography within 3 years for clinical reasons. For the evaluation of the angiographic progress a total of 98 minor and moderate stenoses was measured using digital image processing and automatic contour finding. The change in the angiographic parameters 'percent diameter reduction' (%DR) and 'percent plaque area' (%PA) correlated with on-treatment LDL-Chol levels (%DR change with LDL Chol: r = 0.67, P = 0.0005; %DR change with Chol: r = 0.61, P = 0.002; %PA change with LDL-Chol: r = 0.40, P = 0.037; %PA change with Chol: r = 0.38, P = 0.044), while for HDL-Chol and triglycerides no influence on the angiographic progress could be demonstrated. On the basis of the reproducibility of the measuring methods the patients were classified in the categories 'regression', 'unchanged' and 'progression'. The patients classified as 'regression' (parameter: %DR change) showed an LDL-Chol mean value of 162 +/- 9 mg/dl, whereas those classified as 'unchanged' or 'progression' showed values of 189 +/- 25 mg/dl and 199 +/- 21 mg/dl, respectively (P = 0.014). A negative correlation appeared between the angiographic progress parameters and the initial degree of stenosis. The left ventricular ejection fraction in the second angiography showed relationships to lipoprotein levels and angiographic progress parameters. PMID- 8457257 TI - Plasma Lp(a), apolipoprotein(a) isoforms and acute myocardial infarction in men and women: a case-control study in the Jerusalem population. AB - The relationship of Lp(a) with manifestations of coronary heart disease (CHD) has not been studied extensively in women. There is little information as to the association of the unique Lp(a) apolipoprotein moiety (apo(a)) with CHD in either men or women. We therefore assessed the association of the apo(a) polymorphism and of Lp(a) with first acute myocardial infarction (MI) in a population-based case-control study in Jewish residents of Jerusalem between the ages of 25 and 64. The patients consisted of 238 men and 47 women hospitalized for a first acute MI in the 4 hospitals of Jerusalem serving the population (70% response rate among all first MI patients). The control subjects comprised 318 men and 159 women sampled from the national population registry and who were free of CHD (75% response). Lp(a) and apo(a) were measured in plasma stored at -20 degrees C for 6 24 months. Among men, plasma Lp(a) concentrations were higher in cases than controls in both univariate and multivariate analyses. The elevated risk was limited to the upper fifth of the Lp(a) distribution (unadjusted odds ratio = 1.65, P < 0.01 vs. the lower four quintiles, multivariable odds ratio = 1.82, P < 0.01). Among women, Lp(a) was not elevated in acute MI patients. Apo(a) isoforms with a B, S1 or S2 band (associated with higher Lp(a) values and having lower molecular weights) were more prevalent in female MI cases than controls (unadjusted odds ratio = 2.5, P = 0.016). This association could not be attributed to the higher Lp(a) concentrations associated with these isoforms and was not seen in men. In conclusion, our study points to an association of the apo(a) isoforms with acute MI in women, not evident in this population sample in men. Previously described associations of elevated Lp(a) with acute MI were confirmed in men but not in women. While the role of chance and inadequate statistical power cannot be excluded, the suggestion of a sex difference in the strength of these associations deserves further investigation, as does the question of whether apo(a) phenotype contributes to risk independently of Lp(a) level. PMID- 8457258 TI - A DNA polymorphism for lecithin:cholesterol acyltransferase (LCAT) is associated with high density lipoprotein cholesterol concentrations in baboons. AB - We investigated the effects of a polymorphic PvuII site in the gene for lecithin:cholesterol acyltransferase (LCAT) on serum high density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (apo A-I) concentrations in a population of 750 pedigreed baboons. We also tested for genotype by diet interactions using data on HDL-C and apo A-I concentrations on two diets (chow and high-cholesterol, saturated fat). A significant (P < 0.001) association between the LCAT genotypes and HDL-C levels was observed. On both diets, animals homozygous for the less common allele had HDL-C levels that averaged 18-19% lower than animals homozygous for the more common allele. HDL-C levels of the heterozygotes were intermediate. The LCAT RFLP accounted for approximately 5% of the variation in HDL-C levels on the two diets. We observed no strong evidence for an LCAT genotype by diet interaction effect. PMID- 8457259 TI - Impact of apolipoprotein E polymorphism in determining interindividual variation in total cholesterol and low density lipoprotein cholesterol in Hispanics and non Hispanic whites. AB - The extent of apolipoprotein E (apo E) polymorphism and its effect on eight quantitative risk factors for coronary heart disease (total cholesterol; low density lipoprotein (LDL) cholesterol; total high density lipoprotein and its subfractions, HDL2 and HDL3; triglycerides; fasting glucose and fasting insulin) has been determined in 238 randomly selected Hispanics (120 males and 118 females) and 201 non-Hispanic whites (NHWs) (105 males and 96 females) from the San Luis Valley, Colorado. The frequencies for the E * 2, E * 3 and E * 4 alleles were 0.048, 0.853 and 0.099, respectively, in Hispanics and 0.080, 0.783 and 0.137, respectively, in NHWs. Relatively low frequency of the E * 2 and E * 4 alleles in Hispanics compared with NHWs is consistent with the genetic and anthropologic data that Hispanics have substantial Amerindian admixture. The impact of apo E polymorphism on each quantitative trait was estimated after adjusting for concomitant variables including age, cigarette smoking and body mass index in both genders and pre- or post-menopause status in females. The distribution of eight quantitative traits was analyzed among three common apo E phenotypes, 3-2, 3-3 and 4-3. In Hispanics, significant variability among apo E phenotypes was observed for total cholesterol (P = 0.001) in females only and the apo E polymorphism accounts for 12.4% variation in total cholesterol and 15.2% variation in LDL-cholesterol. In NHWs, significant mean differences among apo E phenotypes were observed for total cholesterol in both males (P = 0.007) and females (P = 0.0004). In NHW males and females, the apo E polymorphism explained 9.2% and 12.4%, respectively, of the variation in total cholesterol, and 15.1% and 6.6%, respectively, of the variation in LDL-cholesterol. In NHWs, borderline significance levels were also noted for phenotype specific differences in HDL2 cholesterol in males (P = 0.04) and females (P = 0.05), for total HDL cholesterol in females (P = 0.02) and HDL3-cholesterol in females (P = 0.06). While the estimated effects of the apo E polymorphism on quantitative traits differ somewhat between Hispanics and non-Hispanic whites, this probably reflects the overall difference in frequencies of the less common alleles in the Hispanics rather than a biological difference in the effects of these alleles on lipid metabolism. PMID- 8457260 TI - Hypocholesterolemic effects of cholestyramine and colestipol in patients with familial defective apolipoprotein B-100. AB - Familial defective apolipoprotein B-100 (FDB) is a dominantly inherited disorder associated with hypercholesterolemia, in which substitution of the amino acid glutamine for arginine at position 3500 in the apoprotein B molecule results in LDL particles which bind poorly to the LDL receptor. To date, patients with FDB have been heterozygous for this disorder and their plasma contains both normal and defective-binding LDL particles, with a predominance of the latter. In the present report, we have compared the hypocholesterolemic effects of bile acid sequestrant therapy (cholestyramine or colestipol) in eight patients with FDB, to the response seen in sixteen patients with heterozygous familial hypercholesterolemia (FH), treated with the same drugs. Concentrations of LDL cholesterol fell by 32.0% in the patients with FDB and by 21.6% in the patients with FH. The results indicate that the hypercholesterolemia of both FDB and FH responds to treatment with bile acid sequestrants. PMID- 8457261 TI - Collagen-linked fluorescence in human atherosclerotic plaques. AB - Advanced glycosylation endproducts (AGE) are intraprotein crosslinks which form in the late stages of the Maillard (browning) reaction. It is unknown whether local changes in AGE-modified collagen occur within arteries. We measured AGE modified collagen as collagen-linked fluorescence (CLF) in human arterial tissue and in various forms of atherosclerotic plaque. All tissues showed single fluorescence peak at excitation wavelength 340 nm and emission wavelength 420-440 nm. CLF in the aorta was 27.9 +/- 8.5 units/mg, in the coronary arteries 25.9 +/- 6.3 units/mg and in the tendon 47.8 +/- 11.5 units/mg. CLF in the skin correlated with CLF in the aorta (r = 0.467, P = 0.025) but not with CLF in coronary arteries (P = 0.935). In areas of aorta covered by superficial plaque, CLF was decreased compared with adjacent, atheroma-free segments (22.2 +/- 5.2 units/mg vs. 27.9 +/- 8.5 units/mg; P = 0.01). The CLF of collagenous plaques correlated with CLF of the atheroma-free regions. Individuals with low to moderate atheroma had lower (20.0 units/mg) CLF in superficial atherosclerotic plaques than patients with severe atheroma (22.5 units/mg; P = 0.0466). Our results indicate that local changes in vascular AGE-collagen concentration occur in atherosclerosis. This finding may have pathogenetic significance in atherosclerosis. PMID- 8457262 TI - Flow cytometric measurement of ceroid accumulation in macrophages. AB - Flow cytometry has been examined as a method for quantitative measurement of the accumulation in macrophages of ceroid, an autofluorescent polymer composed of oxidised protein and lipid. Murine peritoneal macrophages were cultured in the presence of cholesteryl linoleate- or arachidonate-bovine serum albumin (CL/BSA or CA/BSA) complexes. Ceroid accumulation was greater from CA/BSA than from CL/BSA and was dependent upon both time and cell plating density. Inclusion of vitamin E with the complexes diminished the accumulation of ceroid fluorescence after exposure to either CL/BSA or CA/BSA. Controls included exposure of macrophages to BSA, alone and with vitamin E, both of which led to some fluorescence at a similar wavelength to that used to monitor ceroid accumulation (Ex: 351.1-363.8 nm/Em: 490 nm and upwards). Ceroid accumulation can be monitored semi-quantitatively by staining techniques. However, such methods are relatively crude and give little information about the amount of ceroid within cells. Flow cytometry, on the other hand, can give a quantitative assessment of cellular ceroid accumulation, provided experiments are conducted with appropriate controls. The findings are discussed in the context of human atherosclerosis and of future investigation of cell-mediated lipid oxidation and its potential antagonists. PMID- 8457263 TI - Variations in the fatty acid composition of lipid classes from lipoproteins in elderly women. AB - Fatty acid composition of lipid classes and NMR spectra of lipoproteins were compared in 6 young (24-35-year-old) and 6 elderly (79-90-year-old) women. Cholesteryl ester, triglyceride and protein content of LDL in elderly women were significantly higher (+52-57% and +20% for lipids and proteins, respectively) than those observed in young women. HDL lipid levels were similar in the two groups. The proportion of linoleic acid (mainly in cholesteryl esters and phospholipids) of each lipoprotein species was always lower in octogenarians when compared with young females (lowering of 13-28% and 27-46% for cholesteryl esters and phospholipids, respectively). Conversely, the proportions of mono-unsaturated fatty acids (mainly oleic acid) increased in all lipid classes, although this was only significant in cholesteryl esters from each lipoprotein species. NMR spectra of lipoproteins showed a restricted mobility of acyl chain terminal CH3 groups in old women which was significant only in VLDL and HDL3. This suggests that the decrease of linoleic acid could affect the lipid mobility in lipoproteins of elderly women. PMID- 8457264 TI - High density lipoproteins and lipase activity in runners. PMID- 8457265 TI - Plasma lipoprotein(a) levels in patients having chronic renal failure with and without diabetes mellitus. PMID- 8457266 TI - Eliciting patient preferences. PMID- 8457268 TI - Electronic thermometers and nosocomial infections. PMID- 8457267 TI - Reflections on the doctor's anguish. PMID- 8457269 TI - Diagnosing infertility: who is qualified? PMID- 8457270 TI - New recommendations not very different from current practice. PMID- 8457271 TI - Immunization of preterm infants. PMID- 8457272 TI - Nutritional science and the Third World. PMID- 8457273 TI - Malaria therapy: the value of the randomized controlled trial. PMID- 8457274 TI - Researchers and the media. PMID- 8457275 TI - A new 'solid phase' procedure to synthesize immunotoxins (antibody-ribosome inactivating protein conjugates). AB - A method to produce immunotoxins (conjugates comprising of a monoclonal antibody and toxin) using ribosome inactivating protein anchored on an affinity gel derivatized with triazinic dye is described. The adsorbed toxins were activated with 2-imino-thiolane and then conjugated to monoclonal antibody activated by SPDP. The "heterogeneous phase" system offered several advantages, reducing the usually required purification steps and opening a way to automatize the conjugation procedure. PMID- 8457276 TI - Research on isoquinoline derivatives. V--Synthesis and pharmacological evaluation of a series of amidic derivatives of isoquinolin and isocoumarin carboxylic acids. AB - The synthesis of some amidic derivatives of N-methyl-isoquinolin-1(2H)-one-4 carboxylic acid and of isocoumarin-4-carboxylic acid are reported. These compounds have been evaluated for analgesic, antiinflammatory and antipyretic activities. The central nervous system effects have been also investigated. PMID- 8457277 TI - Near infrared reflectance analysis: features and applications in pharmaceutical and biomedical analysis. AB - Growing interest has recently been expressed for the qualitative and quantitative analytical capabilities of Near Infrared Reflectance Spectroscopy (NIRS) in the measurement of physical and chemical parameters. The authors described the details of the method and its applications in the pharmaceutical and biomedical sectors. PMID- 8457278 TI - Synthesis and pharmacological activity of imidazo[2,1-b]benzothiazole acids. AB - We have prepared twelve imidazo[2,1-b]benzothiazole carboxylic and acetic acids by reaction of substituted 2-aminobenzothiazoles with ethyl bromopyruvate and 4 chloroacetoacetate, respectively. The acids, obtained from esters by hydrolysis, were tested for their antiinflammatory, analgesic and ulcerogenic activities. PMID- 8457279 TI - Investigations on the synthesis and properties of arylpiperazinylalkyl derivatives of some dihydro- and tetrahydropyrido[2,3-d]pyrimidines. AB - Synthesis of S- and N-arylpiperazinylalkyl derivatives of ethyl 2-thio-4-oxo-3,4 dihydro- and 2,4-dioxo-1,2,3,4-tetrahydropyrido [2,3-d] pyrimidine-5-carboxylate is described. Some of the obtained compounds are pharmacologically active. PMID- 8457280 TI - Synthesis and some properties of two salsalate derivatives. AB - The synthesis of esters of 2-hydroxy benzoic acid-2-carboxyphenyl ester (salsalate) with guaiacol for the treatment of inflammatory bronchopneumopathies is reported. The antiinflammatory, analgesic and antipyretic activities of these derivatives were evaluated, together with their antioxidant, mucolytic and broncho-bacteriostatic properties in comparison to acetylsalicylic acid. PMID- 8457281 TI - Contribution of major histocompatibility complex (MHC) to upregulation of anti DNA antibody in transgenic mice. AB - Genes linked to the MHC class II contribute to human and murine lupus, but multiple genes are required to produce and upregulate pathogenic autoantibodies. In NZB/NZW mice, nephritogenic IgG anti-dsDNA is provided by NZW (H-2z), but the origin of the upregulating signals is unknown. They could be from NZB (H-2d) or NZW (H-2z) or require heterozygocity. Our aim was to determine whether NZW can provide upregulating signals for the nephritogenic autoantibody introduced to normal mice via transgenes encoding a NZB/NZW IgG2a antibody to DNA. These transgenic mice spontaneously secrete serum IgG2a anti-DNA, some develop clinical nephritis with proteinuria and azotemia, but none die of fatal nephritis. We bred mice to produce offspring of H-2b/d, H-2b/b, H-2b/z and H-2d/z haplotypes (H-2b, H-2d and H-2z derived from C57BL/6, BALB/c and NZW, respectively). Transgenic H 2b/d mice had significantly higher levels of serum anti-DNA antibodies compared with H-2b/b haplotypes from 20 to 40 weeks of age (P < 0.05). However, unlike NZB/NZW mice, they did not show sustained upregulation of anti-DNA antibodies. The serum levels of IgG anti-DNA of transgenic mice declined after 30 weeks of age. In order to determine whether NZW can provide upregulating signals, we introduced the NZW background into transgenic H-2b/d mice in an attempt to increase both quantities of anti-DNA and prevalence of nephritis. However, serum levels of anti-DNA antibodies were similar in transgenic mice of H-2b/z and H 2d/z haplotypes. The anti-DNA levels declined with age in both groups. No mice developed fatal nephritis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457282 TI - The temporal association between gamma delta T cells and the natural history of insulin-dependent diabetes. AB - We previously reported a significant increase in percentages of peripheral blood gamma delta+ T cells in islet cell antibody (ICA) positive relatives of patients with insulin-dependent diabetes (IDD). In the present study, we further characterized this T cell abnormality in a larger group of ICA+ subjects and report that (1) Percentages of gamma delta+ T lymphocytes were significantly increased only in subjects with high ICA titers (> or = 20 JDF units) (P = 0.005) and resulted from an increase in absolute numbers of gamma delta+ T lymphocytes. (2) In these subjects, the increase in gamma delta+ T lymphocytes was associated with an increase in the V gamma 9 V delta 2 subpopulation (r = 0.99). (3) In these same subjects, high percentages of gamma delta+ T lymphocytes were associated with normal beta cell function while low percentages were associated with diminished insulin response. Using 65 microU/ml as the threshold of abnormal intravenous glucose tolerance test (IVGTT) response, percentages of gamma delta+ T lymphocytes could significantly predict IVGTT status in these subjects (P < 0.01). A longitudinal follow-up further suggested that the development of an abnormal IVGTT response and progression to diabetes was associated with a decrease in percentages of gamma delta+ T lymphocytes while patients whose gamma delta+ T cell percentages remained high retained normal beta cell function. Our data therefore suggest that gamma delta+ T lymphocytes and more specifically V gamma 9 V delta 2 T cells are implicated in the autoimmune process leading to diabetes and may have a regulatory role. The monitoring of their percentages in the blood of patients at risk for diabetes may be useful as an additional predictor of diabetes development. PMID- 8457283 TI - The fine specificity of monoclonal anti-DNA antibodies induced in normal mice by immunization with bacterial DNA. AB - To evaluate further bacterial DNA immunization as a model to study antigen drive in the anti-DNA response, the specificity of induced monoclonal anti-DNA antibodies was characterized. A panel of IgM and IgG monoclonal anti-DNA antibodies was produced from spleen cells of BALB/c mice immunized with single stranded DNA from E. coli complexed to methylated bovine serum albumin in complete Freund's adjuvant. The binding of these antibodies to DNA and non-DNA antigens was tested by ELISA to assess their range of polyspecificity. These monoclonal antibodies were found to bind to nucleic acid as well as non-nucleic acid antigens, such as beta-galactosidase, cardiolipin, Ro, La and Sm. These studies demonstrate that anti-DNA antibodies from normal mice, although induced by bacterial DNA, may display a broad range of antigen recognition and thus resemble lupus anti-DNA antibodies, many of which are polyspecific, in their pattern of cross-reactivity. PMID- 8457284 TI - Induction of an anti-vaccine response by T cell vaccination in non-human primates and humans. AB - Experimental and spontaneous autoimmune disease in animals can effectively be prevented and treated by application of pathogenic autoreactive T cells in an attenuated form. This approach has become known as T cell vaccination. T cell vaccination exploits specifically the ability of the immune system to regulate its autoreactive T cells by mechanisms of network control. The success of T cell vaccination in a variety of rodent animal models has raised hopes for its use as an effective and specific therapy in human autoimmune disease. The aim of this study was to induce an anti-T cell response by T cell vaccination in humans and primates as a pre-clinical study into the feasibility and toxicity of T cell vaccination. Using bulk cultures of T cells from the peripheral blood or an inflamed joint, it was possible to induce a T cell response specific for the injected vaccine and its activation state both in rhesus monkeys and in two patients with active rheumatoid arthritis. In one of the patients there was already a spontaneous T cell response against a mitogen driven T cell line from the peripheral blood, but not against a control T cell line specific for tetanus toxoid, suggesting that regulatory T cell networks are operative in patients with autoimmune disease. Significant clinical effects or side-effects were not observed. The results suggest that T cell vaccination in humans is feasible and non-toxic. It is likely to influence an already ongoing regulatory process. Conditions for making T cell vaccination an effective therapy need still to be worked out by further studies both in primates and in less complex human immune processes. PMID- 8457285 TI - Prevention of diabetes and induction of non-specific suppressor cell activity in the BB rat by an immunomodulatory azaspirane, SK&F 106610. AB - Immunomodulatory azaspirane compounds have immunosuppressive activity in animal models of autoimmune disease such as adjuvant-induced arthritis and experimental autoimmune encephalomyelitis. The mechanism of action of azaspiranes appears to be the induction of antigen non-specific (natural) suppressor cell activity. In this study, we tested the azaspirane, SK&F 106610 in an animal model of autoimmune (type 1) diabetes, the BB rat. Oral administration of SK&F 106610 (15 mg/kg/day) to diabetes-prone BB rats, from age 30 days, significantly decreased diabetes incidence at 100 days from 80% (24 of 30 control rats) to 32% (10 of 31 drug-treated rats, P < 0.001). Protection from diabetes by SK&F 106610 was accompanied by decreased lymphocytic infiltration of the pancreatic islets (insulitis). No changes occurred in splenic T cell, B cell or macrophage subsets, or in proliferative responses to the mitogens lipopolysaccharide and concanavalin A (Con-A). Cell mixing experiments in vitro, however, revealed increased antigen non-specific suppressor activity (suppression of splenic lymphoproliferative response to Con-A) in spleens of SK&F 106610-treated rats. The suppressor cell activity was enriched in a low density fraction of splenic cells relatively depleted of T cells, B cells, macrophages and natural killer cells. These results indicate that the azaspirane compound, SK&F 106610 can prevent insulitis and autoimmune diabetes in BB rats and that these actions may be related to the activation of non-specific (natural) suppressor cells. PMID- 8457286 TI - The failure of a combination of thyroid and thymus allografts to prevent the development of autoimmunity in thyroidectomized foetal lambs. AB - Previous experiments have shown that surgical removal of the thyroid gland from the foetal lamb one third of the way through gestation prevents the development of self tolerance towards thyroid-specific determinants. As a result, self thyroid tissue reintroduced into the foetal lamb after maturation of the immune system is not recognized as self and is subject to autoimmune thyroiditis. Furthermore, the transplantation of a thyroid allograft into a foetal lamb immediately after extirpation of its own gland has been shown not to direct the development of self tolerance to thyroid determinants. In the present experiment, foetal lambs were submitted to removal of the entire thyroid gland and the majority of the thymus gland, at 51-54 days of gestation followed by the immediate implantation of thyroid and thymic allografts. The additional implantation of thymus tissue did not affect the previously observed incapacity of a thyroid allograft to facilitate induction of organ-specific tolerance by the thyroid allograft. It was inferred that any T lymphocytes generated within the thymus graft and tolerant of thyroid-specific determinants had not had the capacity to suppress the activity of autoreactive cells generated in the host's thymus. PMID- 8457287 TI - Cross-reactive idiotypes on high affinity IgG class human monoclonal thyroglobulin autoantibodies. AB - Anti-idiotypic antibodies have been developed in rabbits against three high affinity IgG class monoclonal human autoantibodies to thyroglobulin (Tg), which resemble polyclonal Tg antibodies in patients with autoimmune thyroid disease. Antibodies to 1E10 monoclonal anti-Tg (IgG2 kappa) recognised a cross-reactive idiotype (CRI) also present on 1D3 monoclonal anti-Tg (IG1 lambda) and on VB5 monoclonal anti-Tg (IgG2 lambda). The determinant to which anti-1E10 binds appears to involve, at least in part, the binding site for Tg. In contrast, anti idiotypic antibodies raised against VB5 failed to bind to either 1E10 or 1D3, a finding consistent with previous studies on serum polyclonal Tg antibodies, which suggested that such antibodies exhibit a mixture of private and cross-reactive idiotypes. The observed sharing of idiotypic determinants was not related to subclass, light chain type or expression of a particular VH gene family in the heavy chain. Although binding of the anti-idiotypic antibodies to Tg antibodies in a panel of patients (including the donors of the lymphocytes used to produce the monoclonal antibodies) could not be detected, the monoclonal antibodies are representative of the donor patients' serum Tg antibodies, both in terms of IgG subclass and functional affinity. Thus these idiotypes may be present in patients' sera at levels below the detection limits of the assays employed. Cross reactive regulatory idiotypes in mice often constitute a minor component of the anti-Tg repertoire. Consequently, it is possible that low levels of a CRI, such as the 1E10 CRI, may be involved in the regulation of the autoimmune response to Tg in man. PMID- 8457288 TI - Anti-idiotype antibodies to anti-mitochondrial antibodies in the sera of patients with primary biliary cirrhosis. AB - Idiotype-anti-idiotype interactions were investigated in the sera of patients with primary biliary cirrhosis (PBC), which is characterized by the presence of circulating anti-mitochondrial antibodies (AMA). A mouse monoclonal antibody, CPZ674, has been raised to the E2 component of the pyruvate dehydrogenase complex (PDC), which is the target antigen of AMA. CPZ674 recognizes one of the epitopes recognizable by AMA, as demonstrated by competitive Western blotting. Anti idiotypic antibodies in PBC sera were detected either by their specific binding to CPZ674 in an ELISA or by the formation of idiotype-anti-idiotype complexes with CPZ674, detected using chromatography on a Sephacryl-300 column and by a polyethylene glycol precipitation method. The specificity of the anti-idiotypic antibodies to AMA was shown by their ability to inhibit the binding of AMA to PDC, but not the binding of other autoantibodies to their relevant autoantigens. We have therefore produced evidence for the existence of idiotype-anti-idiotype interactions in PBC, but whether these anti-idiotypic antibodies are involved in the control of AMA is unknown. PMID- 8457289 TI - Correlation between lack of bone Gla protein mRNA expression in rat transplantable osteosarcomas and expression of both c-fos and c-jun proto oncogenes. AB - Alkaline phosphatase (AP) activity and expression of bone Gla protein (BGP), c fos, and c-jun were compared in two transplantable osteosarcomas with high potentials for metastasis to the lung. The original spontaneous osteosarcoma (SOS) gradually became histologically undifferentiated, losing its osteogenic activity during serial transfer, whereas the chemical (4-hydroxyaminoquinoline 1 oxide)-induced osteosarcoma (COS) retained osteogenesis. The two osteosarcomas showed similar doubling times and levels of lung metastasis, and strong AP activity was detected on the cell membranes of both. Northern blot analysis revealed that lack of BGP mRNA expression was associated with expression of both c-fos and c-jun proto-oncogenes in SOS. In contrast, neither c-fos nor c-jun mRNAs were detected but BGP mRNA was expressed in the case of COS. These results suggest that the c-fos and c-jun genes may suppress the expression of BGP mRNA relevant to differentiation and osteoid formation in rat osteosarcomas. However, this does not appear to be directly related to proliferative or metastatic biological behavior. PMID- 8457290 TI - Quantitation of 2-amino-3-methylimidazo[4,5-f]quinoline and 2-amino-3,8 dimethylimidazo[4,5-f]quinoxaline DNA adducts in specific sequences using alkali or uvrABC excinuclease. AB - 2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,8-dimethylimidazo[4,5 f]quinoxaline (MelQx) are carcinogens found in cooked meats that form DNA adducts upon metabolic activation. Purified DNA from Chinese hamster ovary (CHO) cells was reacted in vitro with the active metabolites N-acetoxy-IQ or N-acetoxy-MelQx, and the adduct levels in the 5' dihydrofolate reductase (DHFR) gene and downstream region were quantitated by Southern hybridization. Adducted and restricted DNA was treated with Escherichia coli uvrABC excinuclease or alkali (0.1 N NaOH, 37 degrees C, 60 min) to incise DNA at IQ and MelQx adduct sites. The DNA was then denatured with formamide, electrophoresed on a neutral agarose gel, transferred to a support membrane, and hybridized with sequence-specific DNA probes. Both uvrABC and alkali reduced the intensity of Southern hybridization in proportion to the number of IQ or MelQx adducts in DNA, indicating that these adducts are substrates for uvrABC and that they form alkali-labile lesions in DNA. IQ and MelQx adduct levels were the same in the 5' DHFR gene and in the downstream region. Southern hybridization analysis of pBR322 containing known levels of IQ or MelQx adducts showed that the efficiency of cutting IQ or MelQx adducts by uvrABC excinuclease and alkali was approximately 30% and 15%, respectively. 32P-postlabeling studies examining adduct level in bulk DNA further showed that the adduct profiles were identical in pBR322, CHO DNA, and cultured CHO cells exposed to the reactive metabolites of IQ or MelQx. The results indicate that IQ and MelQx adducts can be quantitated in specific genomic sequences and that this method should be directly applicable to studies of gene specific repair of these adducts in cultured cells. PMID- 8457291 TI - Creation of an active estrogen-responsive element by a single base change in the flanking sequence of a cellular oncogene: a possible mechanism for hormonal carcinogenesis? AB - Estrogens are considered to act as promoters in a multistep process of hormonal carcinogenesis, although the molecular mechanisms by which these hormones act in tumorigenesis are unclear at present. Estradiol is known to induce expression of certain proto-oncogenes, and this led us to examine potential regulatory regions of the cellular c-fos oncogene. The 5'-flanking region of the murine c-fos contains a 13-bp palindromic sequence (GGTCTnnnAGACC) with striking homology to the consensus estrogen-responsive element (ERE) GGTCAnnnTGACC. However, the c-fos sequence did not bind the human estrogen receptor or confer hormonal responsiveness in a yeast-based transcriptional test system. Importantly, a single base change in the fifth position of the c-fos sequence (GGTCTnnnAGACC to GGTCA/GnnnAGACC) produced an element that bound the estrogen receptor and conferred estrogen-dependent transcriptional activation of a reporter gene. This suggests a specific hypothesis by which estrogens could act as tumor promoters. In this paradigm, the regulatory region of the cellular oncogenes, tumor suppressor genes, and growth-factor genes contain inactive sequences with close homologies to hormone-responsive elements. Initiation occurs when some agent (e.g., a chemical carcinogen) causes a mutation in such a sequence to create a functional hormone-responsive element. Estrogens, acting through their receptors and the mutated element, can then activate the target gene to stimulate cell proliferation and increase the population of initiated cells. PMID- 8457293 TI - Lack of mutations of the p53 tumor suppressor gene in hepatocellular carcinomas induced in rats by a peroxisome proliferator. AB - Immunohistochemical, immunoblotting, and DNA-sequencing analyses were performed on hepatocellular carcinomas induced in rats chronically fed BR931, a peroxisome proliferator, to determine whether the tumors carried mutations or other alterations of the p53 gene. None were detected. Inactivation of this tumor suppressor gene does not appear, therefore, to be involved in the carcinogenicity of BR931, a nongenotoxic chemical hepatocarcinogen. PMID- 8457292 TI - Direct growth stimulation of normal human epithelial cells by mutant p53. AB - We developed a high-titer amphotropic retroviral vector that expresses mutant (Ala143) human p53 to test directly the response of genetically normal human epithelial cells to p53 mutation. Contrary to our prediction, we found that in pancreatic epithelium (whose tumors display a high frequency of p53 mutation) but not in thyroid (whose tumors show an exceptionally low mutation frequency), expression of mutant p53 induced a dramatic, though self-limiting, proliferative response. This result questions the assumption that p53 mutation is relevant only to the later stages of tumorigenesis. PMID- 8457294 TI - [Nursing documentation: consensus in practice (2). Its application in stages 1 and 2: Mrs. De Wit]. PMID- 8457295 TI - [Nursing and law. Carrying out a campaign: how far can you go?]. PMID- 8457296 TI - [Environment and care (7). Nutrition in a polluted environment]. PMID- 8457297 TI - [Nursing diagnosis as cornerstone. 5 American researchers on nursing diagnosis. Interview by Leo Regeer]. PMID- 8457299 TI - Tympanostomy tubes and audiograms. PMID- 8457298 TI - [Cancer pain: nurses' attitudes]. PMID- 8457300 TI - Advances in palatoplasty. PMID- 8457301 TI - Temporalis muscle for facial reanimation. A 13-year experience with 224 procedures. AB - A procedure for temporalis muscle transposition was used to reanimate the paralyzed face in 219 patients. In most cases, facial paralysis had followed an operation to remove an acoustic tumor. Analysis of the results showed this procedure to be highly successful and the method of choice, alone in cases of long-standing facial paralysis or to augment the effects of facial nerve grafting or hypoglossal-facial nerve anastomosis, in reanimating the mouth. It was successful in restoring a smile to 80% of the 219 patients and provided overall improvement in mouth function in 96%. Complications occurred in 21% of patients, with the most common being infection (12% of patients). Since one of us began to use the procedure to reanimate the eye and mouth, results of temporalis muscle transposition have been improved by the following: (1) using the procedure to reanimate the mouth only; (2) performing revision surgery, most often tightening the corner of the mouth (25% of patients), as indicated; (3) transposing only the midsection of the muscle; (4) implanting a prefabricated Silastic prosthesis to fill the muscle defect; (5) when indicated, lengthening the muscle with polytef (Gore-Tex+); and (6) placing the muscle in a tunnel lateral to the superficial musculoaponeurotic system to avoid injuring the underlying facial nerve should some spontaneous recovery of facial nerve function be possible. PMID- 8457302 TI - The subcranial approach for fronto-orbital and anteroposterior skull-base tumors. AB - We describe 78 patients with fronto-orbital and sphenoethmoidal tumors surgically treated with the subcranial approach. This approach was developed by us in 1978 primarily for the treatment of skull-base trauma and craniofacial anomalies. Since 1980, we have extended the indications to include tumor resections. This extended anterior exposure of the anterior fossa skull base, including the sphenoidal and clival planes, enables an en bloc tumor removal obviating the transfrontal approach or lateral rhinotomy. In contrast with the conventional transcranial approach, the anterior subcranial approach provides an extended exposure of these locations, avoiding frontal lobe retraction. Reduction of complications, such as recurrent cerebrospinal fluid leaks, postoperative brain edema, damage to cranial nerves, and infection plus decreased hospitalization, are the major advantages of this procedure. PMID- 8457303 TI - Open reduction-fixation of mandibular subcondylar fractures. A review. AB - From 1973 to 1990, 392 mandibular subcondylar fractures were treated at the University of California, Davis, by the Otolaryngology Department. Of these, 17% were handled by open reduction and internal fixation. Twenty-one patients from this group were located for follow-up at an average interval of 64 months. Retrospective review shows the operation to be safe, with few complications and no permanent sequelae. Patient examination often revealed abnormalities of occlusion and mandibular function; however, these objective findings did not correlate well with patients' relative lack of subjective complaints. An 86% incidence of roentgenographic evidence of condylar disease after open reduction and internal fixation was found. We question the long-term efficacy of open reduction and internal fixation in restoring fracture alignment and maintaining mandibular height given the high rate (86%) of condylar disease in our patient population. PMID- 8457304 TI - The effect of tissue expansion on the random flap viability and wound tensile strength of previously irradiated rabbit skin. AB - Tissue expansion facilitates coverage of cutaneous defects both through the generation of additional skin surface area and by increasing random flap length/width viability factors. The opportunity to apply tissue expansion techniques to head and neck defects within previously irradiated skin fields continues to increase. To study the effect of tissue expansion on the cutaneous perfusion and wound-healing capacity of irradiation-damaged skin, rabbit scalps were subjected to 5 weeks of fractionated radiation followed at 4 months by prolonged tissue expansion. Standardized random flaps were then created and reset within the expanded skin and analyzed in parallel with nonirradiated and nonexpanded control animals. Flap viability as expressed by area and mean maximum length was determined at 10 days postwounding followed by determination of wound breaking strength. Irradiated tissues demonstrated a significantly reduced flap viability that was significantly increased by expansion. However, tissue expansion-related increases in flap length exceeded those expressed as percent of total area surviving for irradiated animals. Tissue expansion resulted in significant increases in wound tensile strength only in nonirradiated animals. These findings suggest that, compared with controls, several of the benefits of tissue expansion are less appreciable in radiation-damaged skin. PMID- 8457305 TI - Otitis media in the Republic of Palau. A case-series study. AB - Race is a known epidemiologic determinant for the development of otitis media. This study assessed the severity of otitis media in a subpopulation (N = 73; mean age, 13.2 years) receiving care from the ear clinic in the Republic of Palau, a US Trust Territory, through a questionnaire and an otologic examination. The mean age of patients with otorrhea (2.5 years) was found to be significantly different from the mean age at which they began to swim (4 years). Otitis media-related sequelae were found to involve more than half of ears or subjects examined. No statistical difference was noted when various patient characteristics were compared with the severity of disease. Our clinical impression is that this subpopulation is severely affected by otitis media and its sequelae. Prospective studies are required to identify risk factors present in the population at large. PMID- 8457306 TI - Defects in cellular immunity in chronic upper airway infections are associated with immunosuppressive retroviral p15E-like proteins. AB - Partial defects in cell-mediated immunity have been shown in patients with chronic purulent rhinosinusitis. These defects, ie, impaired delayed-type hypersensitivity (type IV) skin reactions on commensal microorganisms of the upper respiratory tract and impaired chemotactic responsiveness of monocytes, are associated with the presence of immunosuppressive retroviral p15E-like proteins in the serum of these patients. In this study, we tested whether partial defects in cellular immunity could also be demonstrated in other groups of patients with chronic upper airway infections. Therefore, three well-characterized groups of patients with chronic upper airway infections were investigated: (1) patients with primary ciliary dyskinesia, a congenital disorder of respiratory cilia, resulting in absence of mucociliary clearance and, as a consequence, in chronic respiratory infections; (2) patients with chronic rhinosinusitis, with normally functioning cilia and with nasal polyps; and (3) patients with chronic rhinosinusitis, with normally functioning cilia but without nasal polyps. Our results show that in all three groups, most patients (87%) had defects in cellular immunity associated with the presence of p15E-like proteins in their serum. These results indicate that during chronic infections of the upper respiratory tract, immunosuppressive retroviral p15E-like proteins are found, which are probably responsible for the partial immune defects found in these patients. PMID- 8457307 TI - Control of the temporal aspect when considering risk factors for acute otitis media. AB - A random sample of 2512 children was monitored to age 2 years to study the biologic effects of various risk variables on acute otitis media using a new dynamic modeling that controls both the confounding effects and time dependency. Dynamic modeling proved to be superior to conventional approaches, both the random and systematic error being much smaller and the effect estimates being biologically interpretable. The major risk factors were the existence of a previous episode of acute otitis media in general (odds ratio, 2.03; 95% confidence interval [Cl], 1.81 to 2.25) or particularly during the preceding 3 months (odds ratio, 3.74; 95% Cl, 3.40 to 4.10) and attending a day nursery (odds radio, 2.06; 95% Cl, 1.81 to 2.34). As the form of day care is the only modifiable risk variable of significant importance and previous episodes entail a risk of future ones, infants should be cared for at home, particularly after they have already experienced an episode of acute otitis media. PMID- 8457308 TI - Single treatment approaches to benign paroxysmal positional vertigo. AB - OBJECTIVE: To determine the effectiveness of two different physical therapy approaches for benign paroxysmal positional vertigo. DESIGN: Randomized study. SETTING: Outpatient clinic. PATIENTS: Consecutive sample of 60 patients with benign paroxysmal positional vertigo. INTERVENTION: Patients received either a single treatment based on the hypothesis that the vertigo and nystagmus of benign paroxysmal positional vertigo are due to debris adhering to the cupula of the posterior semicircular canal (cupulolithiasis) or a single treatment based on the hypothesis that the debris is free floating in the long arm of the posterior canal (canalithiasis). Patients were reevaluated 1 to 2 weeks after the treatment and again 4 to 6 months later. OUTCOME: Treatment outcome was classified as either asymptomatic, more than 70% improved as rated by the patient, or no change. RESULTS: The treatment designed for cupulolithaisis resulted in remission of vertigo and nystagmus in 70% of the patients and in improvement of the symptoms in another 20%. The treatment designed for canalithiasis resulted in remission of vertigo and nystagmus in 57% of the patients and in improvement in another 33%. There was no statistically significant difference between treatments. CONCLUSIONS: These single-treatment approaches are equally effective treatments for benign paroxysmal positional vertigo. Further studies are needed to look at the long-term effectiveness of these treatments. PMID- 8457309 TI - Inner ear barotrauma in scuba divers. A long-term follow-up after continued diving. AB - Divers who suffer inner ear barotrauma are usually counseled to permanently avoid diving, reasoning that the injured inner ear is at increased risk of further damage. Twenty patients who suffered inner ear barotrauma while diving, but continued to dive against medical advice, were assessed on an interim basis for 1 to 12 years. As difficulty equalizing the ears during the barotraumatic event was a universal finding, prior to resuming diving, all patients were reinstructed on methods of maximizing eustachian tube function. No further deterioration of cochleovestibular function was noted. Based on these preliminary results, we conclude that recommending no further diving after inner ear barotrauma may be unnecessarily restrictive. PMID- 8457310 TI - Progressive sensorineural hearing loss in association with distal renal tubular acidosis. AB - The autosomal recessive inherited syndrome of distal renal tubular acidosis and sensorineural hearing loss may present in one of two distinct fashions. The rare adolescent form is characterized by mild renal tubular acidosis, mild to moderate sensorineural hearing loss, and otherwise normal growth and development. The more common infantile type typically presents in the first year of life with failure to thrive, acidosis, and a more severe sensorineural hearing loss. In this report, progression of sensorineural hearing loss is documented for the first time in two siblings with the infantile variant. This association suggests that all children with distal renal tubular acidosis should undergo sequential audiologic evaluations with the institution of appropriate amplification and educational intervention as needed. PMID- 8457311 TI - Repair of the facial nerve using freeze-thawed muscle autografts. A surgical model in the sheep. AB - In five sheep, repair of the right facial nerve in the preparotid region was undertaken using freeze-thawed muscle autografts aligned coaxially in the nerve gap. The sheep were reviewed at 240 days. Nerve conduction velocities were measured in the distal buccal nerve after stimulation proximal to the repair site and compared with an equivalent site on the normal side. Although mean peak conduction velocities were reduced on the repaired side, electrophysiologic evidence showed regeneration in all five cases. Normal and repaired nerves were retrieved for histologic study. Anatomic indices of regeneration were compared using morphometric techniques. As seen in other methods of nerve repair, axon and fiber diameters with normal myelination were reduced on the operated-on side. The muscle graft thus compares favorably with other surgical techniques over the gap lengths considered herein. PMID- 8457312 TI - Pathologic quiz case 2. Pneumocystis carinii infection of the external auditory canal. PMID- 8457313 TI - Pathologic quiz case 1. Vagal paraganglioma. PMID- 8457314 TI - Perilymphatic fistulas: state of the art. PMID- 8457315 TI - The treatment of recurrent tonsillitis with Broncasma Berna instead of tonsillectomy. PMID- 8457316 TI - Tinnitus and vertigo. PMID- 8457317 TI - Establishing relevant ozone standards to protect vegetation and human health: exposure/dose-response considerations. AB - For assessing the efficacy of a specific form of the National Ambient Air Quality Standard for O3, those exposure patterns that result in vegetation and human health effects must be identified. For vegetation, it has been found that the higher hourly average concentrations should be weighted more than the lower concentrations. Controlled human exposure work supports the suggestion that concentration may be more important than exposure duration and ventilation rates. It has been indicated in the literature that the current form of the federal O3 standard may not be appropriate for protecting vegetation and human health from O3 exposures. The proposed use of the cumulative index alone as a form of the standard may not provide sufficient protection to vegetation. An extended-period average index, such as a daily maximum 8-hour average concentration, may not be appropriate to protect human health because of the reduced ability to observe differences among hourly O3 concentrations exhibited within exposure regimes. For both vegetation and human health effects research, additional experimentation is required to identify differences in responses that occur when ambient-type exposure regimes are applied. Any standard promulgated to protect vegetation and human health from O3 exposures should consider combining cumulative exposure indices with other parameters so that those unique exposures that have the potential for eliciting an adverse effect can be adequately described. PMID- 8457318 TI - Emissions of volatile organic compounds from new carpets measured in a large scale environmental chamber. AB - This study was undertaken to quantify the emissions of volatile organic compounds (VOCs) released by new carpets. Samples of four typical carpets, including two with styrene-butadiene rubber (SBR) latex adhesive and two with different backings, were collected from the finish lines at manufacturers' mills. Individual VOCs released from these samples were identified, and their concentrations, emission rates and mass emissions were measured under simulated indoor conditions in a 20 m3 environmental chamber over one week periods. Concentrations and emission rates of VOCs emitted by a new SBR carpet were also measured in a house. The carpets emitted a variety of VOCs. The two SBR carpets primarily emitted 4-phenylcyclohexene (4-PCH), the source of "new carpet" odor, and styrene. The concentrations and emission rates of 4-PCH were similar for the two carpets, while the styrene values varied significantly. The carpet with a polyvinyl chloride backing emitted formaldehyde, vinyl acetate, isooctane, 1,2 propanediol, and 2-ethyl-1-hexanol. Of these, vinyl acetate and propanediol had the highest concentrations and emission rates. The carpet with a polyurethane backing primarily emitted butylated hydroxytoluene. With the exception of formaldehyde, little is known about the health effects of these VOCs at low concentrations. PMID- 8457319 TI - An assessment of air quality impacts of fires associated with fire fighting operations. AB - Fire fighters in Canada's navy must undergo regular training with fires from simulated helicopter crashes. Visible emissions from these fires often create health concerns in surrounding communities. This paper presents air quality implications of plume dispersion associated with "helicopter fires." Evaluations involved measuring plume rise, estimating emissions, dispersion modeling and ambient monitoring. Results of the evaluation provided ground-level concentration estimates of plume particulate matter, oxides of nitrogen, hydrogen fluoride, carbon monoxide, 22 metals, 15 PAH and 13 VOC. The study showed that the air quality impact of the fire fighting training is much lower than the relevant time weighted averages established to protect workers' health. This paper will be of interest to people in environmental protection agencies because it demonstrates the effects of fire fighting operations that must frequently occur as part of training exercises. PMID- 8457320 TI - Interferon-gamma and resistance to bacterial infections. AB - Since its initial description as an antiviral, it has become clear that Interferon-gamma (IFN-gamma) has potent immunoregulatory and cell growth regulatory activities. As a result of these additional activities, it is now apparent that IFN-gamma plays a major role in regulation of bacterial infections. IFN-gamma can be both induced by bacteria and bacterial products; endogenous IFN gamma production has been shown to play a protective role in the natural host response to several bacterial infections; and administration of exogenous IFN gamma is effective in the prevention and treatment of bacterial infections in numerous animal model systems. Although it is now clear that IFN-gamma plays a role in regulation of bacterial infections, the mechanisms of its anti-bacterial effects in vivo remain to be established due to the pleiotropic nature of IFN gamma activity. PMID- 8457321 TI - Demonstration of toxin A and B by polymerase chain reaction and McCoy cell assay in clinical isolates of Clostridium difficile from Denmark. AB - A polymerase chain reaction (PCR) for demonstration of gene fragments of Clostridium difficile was established. One hundred and sixty-eight clinical isolates of C. difficile from three population groups were tested for production of cytotoxins by McCoy cell line assay (MCA) and for fragments of toxin A and B genes by PCR. The fragments for PCR amplification were at the 5' end of the toxin genes, which was found to be specific for C. difficile. Full agreement between the PCR and MCA results was found with respect to toxicity. Fifty-eight of the 168 strains were cytotoxin positive. Isolates from 41 normal healthy children did not differ regarding cytotoxicity compared to isolates from hospitalized children. In adult hospitalized patients a much higher frequency of toxin producing isolates was found. In two strains from two children, not of the same family, only the toxin A gene fragment was demonstrated, indicating that some strains of C. difficile only harbour the gene for enterotoxin. When two isolates from different periods of time were tested from 36 of the healthy children, a variation in cytotoxicity was found: in seven children strains changed from non toxic to toxic and in four vice versa. This may be explained by a fluctuating colonization of toxic and non-toxic C. difficile strains, or it may indicate the need for examination of more than one strain from a positive faecal sample to demonstrate cytotoxicity. PMID- 8457322 TI - Stereological estimation of nuclear volume in benign and atypical meningiomas. AB - A stereological estimation of nuclear volume in benign and atypical meningiomas was made. The aim was to investigate whether this method could discriminate between these two meningeal neoplasms. The difference was significant and it was moreover seen that there was no overlap between the two groups. The results demonstrate that atypical meningiomas can be distinguished from benign meningiomas by an objective stereological estimation of nuclear volume. PMID- 8457324 TI - Chlamydial cervicitis: role of culture, enzyme immunoassay and Giemsa cytology in diagnosis. AB - Three different laboratory tests were carried out to find the occurrence of chlamydial infections in a selected group of 150 female patients presenting clinically with cervicitis. The tests included isolation using a cell culture system, enzyme immunoassay (EIA) for antigen detection and Giemsa cytology of endocervical smears. Contrary to earlier reports on cytological diagnosis of chlamydial cervicitis, endocervical smears stained by Giemsa stain and EIA for antigen detection were found to be of comparable sensitivity and specificity (73.1% and 86.3% for smear, and 76.1% and 90.9% for EIA, respectively) when cell culture was used as the gold standard. PMID- 8457323 TI - In vitro antimicrobial susceptibility testing of rapidly growing mycobacteria using the tablet diffusion method: resistance pattern of Norwegian Mycobacterium fortuitum and Mycobacterium chelonae isolates. AB - Thirty-one Norwegian clinical isolates of rapidly growing mycobacteria classified as Runyon's group IV, including 20 Mycobacterium fortuitum and 11 Mycobacterium chelonae strains, were found resistant to a majority of tuberculostatic agents. Minimal inhibitory concentration (MIC) was determined for twelve other antimicrobial agents: amikacin, tobramycin, streptomycin, cefoxitin, imipenem, norfloxacin, ciprofloxacin, doxycycline, erythromycin, fusidic acid, co trimoxazole and capreomycin. The agar plate dilution method was employed and compared with the agar tablet diffusion method. Regression lines were established correlating MIC values and inhibition zones. The agar tablet diffusion method was found to be a simple and useful method for testing antimicrobial susceptibilities of M. fortuitum and M. chelonae, and a good correlation between MIC values and zone sizes with twelve antimicrobial agents was revealed. Correlation coefficients for most of these antimicrobial agents were around -0.90. M. chelonae was generally more resistant than M. fortuitum. Four antimicrobial agents, capreomycin, norfloxacin, ciprofloxacin and amikacin, showed differences between M. fortuitum and M. chelonae large enough to allow the zone diameter to be used diagnostically. PMID- 8457325 TI - Antibody profiles to the group B streptococcal beta antigen in maternal and infant paired sera. AB - Antibody profiles to the purified beta antigen of the c protein of group B streptococci (GBS) were studied by ELISA and Western immunoblot (WB). The sera from 139 parturient women colonized with GBS, 35 non-colonized parturients and their newborn infants were studied by ELISA; WB was done on 76 maternal and 26 infant sera. Enzyme-labeled anti-IgA (alpha), -IgG (gamma), -IgM (mu), or -IgG (H&L) were used as secondary antibodies. A high prevalence of antibody to the beta antigen was observed by both ELISA and WB among parturient women and their newborns. IgG (H&L) ELISA titers > or = 200 were found in 84% and > or = 800 in 31% of the maternal sera. A significantly higher percentage of women colonized than those non-colonized with GBS had IgG (gamma) titers > or = 800. A significantly higher percentage of women colonized with c protein-positive than c negative strains of GBS had IgG (H&L) titers > or = 3200. Twelve of 27 women with IgM antibody to the beta antigen also had IgG (gamma) titers > or = 800 and were, in addition, colonized with GBS. Multiple molecular forms of the antigen from 25 to 140 kDa were blotted by the maternal and infant sera. Concordance in the IgG but not in IgA or IgM antibody profiles of maternal and infant paired sera was observed in the overall blotting patterns and ELISA titers. The same titer as the mother was found in 55% of the infant sera and within one dilution in 97%. This suggests active transfer of IgG antibody to the beta antigen across the placenta from mother to baby. PMID- 8457326 TI - Intracellular levels and extracellular release of lysosomal enzymes from peripheral blood monocytes in pulmonary tuberculosis patients. AB - The intracellular activity and extracellular release (basal and latex-stimulated) of B-glucuronidase (BG) and N-acetylglucosaminidase (NAG), measured fluorimetrically, were observed to be significantly (P < 0.05) higher in blood monocytes (BM) of untreated pulmonary tuberculosis (TB) patients compared to those of age- and sex-matched controls and Mantoux-positive subjects without any evidence of active disease. After completion of antituberculous therapy, BG and NAG activities declined appreciably (P < 0.05) and their levels became comparable to those in control subjects. The present results suggest the potentiation of the oxygen-independent defense mechanism of BM in pulmonary TB. PMID- 8457327 TI - Survival and ultrastructural changes of Helicobacter pylori after phagocytosis by human polymorphonuclear leukocytes and monocytes. AB - Few studies have been carried out on the phagocytosis and killing of Helicobacter pylori by both polymorphonuclear leukocytes (PMNs) and monocytes. In this study, H. pylori was incubated for up to 60 min either alone or with phagocytes in the presence or absence of human serum. Both non-immune serum and immune serum were used. Reduction in the number of H. pylori, which corresponds to the killing of H. pylori, was analysed by a colony count and ultrastructural changes were studied by electron microscopy. No reduction in the number of H. pylori was found when the bacteria were incubated alone or with phagocytes in the absence of serum. It is remarkable that unopsonized H. pylori was phagocytosed. When immune serum was added to the suspensions of bacteria and phagocytes, the killing rate of H. pylori was found to depend on the ratio of H. pylori to phagocytes. Thus an excess of monocytes reduced the number of H. pylori, whereas an excess of PMNs resulted in complete killing of H. pylori. On incubation with PMNs and serum, ultrastructural changes were observed in the majority of the bacteria whether they were phagocytosed or not. Controls without serum did not show any changes in the morphology of H. pylori, indicating that components in the serum play an important role in the phagocytosis and killing of H. pylori. In contrast, several of the phagocytosed bacteria were found to be unaffected after incubation with monocytes and serum. Such preparations often contained large aggregates of platelets surrounding unaffected H. pylori. In the gastric mucosa, H. pylori is often found in excess as compared to the phagocytes. If these results can be compared to the situation in vivo, the phagocytes seem to be ineffective in the killing of H. pylori, and other immune mechanisms may therefore be of importance for the elimination of H. pylori from the gastric epithelium. The possible intracellular survival of H. pylori should be taken into account when treatment regimes for H. pylori infections are chosen. PMID- 8457328 TI - Thymic epithelial abnormalities in patients with congenital heart disease and Down's syndrome. AB - Among 85 children (< 5 years) operated on for congenital heart disease, we found 15 with structural changes of the thymus consisting of epithelial ducts and cysts. Nine of the children had Down's syndrome. In only two of these did we find epithelial abnormalities. In conclusion, these changes were not more frequent in children with Down's syndrome than in other patients with congenital heart disease. PMID- 8457329 TI - Hypoxia-associated proteins in human cells cultivated in vitro: lack of association with hypoxia-induced cell cycle regulation. AB - The synthesis of proteins expressed in human NHIK 3025 cells following exposure to extremely hypoxic conditions (< 4 ppm O2) has been studied. Populations of cells, either in exponential growth or synchronized by the method of detaching mitotic cells, were exposed to extremely hypoxic conditions for up to 20 h. The rate of total protein synthesis was measured at various time points after reoxygenation, and it appeared to be relatively constant and similar to the control level. The protein expression in cells was studied by pulse labelling for 1 h with [35S]-methionine, and subsequently visualized by SDS-PAGE and autoradiography. Six proteins appeared to have a changed expression after exposure to extreme hypoxia as compared to control cells; four of them (45, 80, 100 and 150 kD) showed increased, while two (46 and 90 kD) showed decreased expression. The response of these proteins to extreme hypoxia seems to be relatively slow, i.e. with half-times of several hours. Since extreme hypoxia influences cell cycle progression by instantaneous blockage at the G1/S border as well as halting DNA synthesis in S cells, these proteins can hardly cause these effects. Neither is the altered expression of these proteins due to the accumulation of G1 cells caused by hypoxia. PMID- 8457330 TI - Remnant kidney pathology after five-sixth nephrectomy in rat. II. Electron microscopy study. AB - In Wistar male rats, hypertension was induced by 5/6 nephrectomy (5/6N). Electron microscopy revealed an increase in the number of epithelial cells on the Bowman's capsule during the early stages (4 weeks). After 8 and 12 weeks, frequent adhesion was observed between the glomerular tuft and Bowman's capsule. The abnormal podocytes showed nuclear irregularities and distortions. Characteristic foot process fusion formed cytoplasmic plates. There was a considerable increase in mesangial matrix and cells. No immune deposits or breaks in the glomerular basement membrane were observed. In the endothelial cells, the fenestration disappeared in sclerosed glomeruli. Some capillary loops were obliterated by fibrin, macrophages and foam cells. These findings combined with our previous light microscopy and immunofluorescent observations suggest a non-immunogenic glomerular sclerosis. PMID- 8457331 TI - Hypothyroidism and anti-endothelial cell antibodies. AB - Because of our previous demonstration of anti-endothelial cell antibodies (AECA) in patients with insulin-dependent diabetes mellitus and their association, in this condition, with thyroid disease, we sought these antibodies in patients with suspected thyroid dysfunction using an enzyme immunoassay with human umbilical vein endothelial cells as the substrate. AECA were found in 5/120 (4.2%) patients with normal and 15/97 (15.4%) with abnormal thyroid function. The increased prevalence in the latter group was due to a highly significant association between the presence of AECA and raised levels of TSH. We conclude that a highly significant correlation exists between the levels of AECA and TSH, but not between those of AECA and fT4. Patients with hypothyroidism as defined by high levels of TSH have AECA significantly more often than patients with low or normal TSH (22.2% versus 2.8% and 5.8%). PMID- 8457332 TI - A selective system for lacZ- phage using a galactose-sensitive E. coli host. PMID- 8457333 TI - Two new phagemid vectors for site-directed mutagenesis and expression in E. coli. PMID- 8457334 TI - Spin dialysis desalting of small protein samples in a membrane-bottomed 96-well microplate. PMID- 8457335 TI - Rapid separation of DNA from ethidium bromide and cesium chloride in ultracentrifuge gradients by a desalting column. PMID- 8457336 TI - Zinc deficiency in antibody-conjugated alkaline phosphatase inhibits enzyme activity in ELISAs. PMID- 8457337 TI - Allele-specific oligonucleotide probes for mRNA. PMID- 8457338 TI - Rapid and simple phage DNA isolation. PMID- 8457339 TI - Concentration of primer and template qualitatively affects products in random amplified polymorphic DNA PCR. PMID- 8457340 TI - Overcoming GC compression in nucleotide sequencing. PMID- 8457341 TI - Preparation of denatured plasmid templates for PCR amplification. PMID- 8457342 TI - A rapid procedure for preparing high molecular weight DNA from yeast for Southern analysis. PMID- 8457343 TI - Two-step "hot" PCR amplification of GC-rich avian c-myc sequences. AB - A new two-step cycle PCR method has been developed for amplification of GC-rich DNA sequences. Using this method, termed "hot PCR," 111 and 179 bp regions (GC contents of 74% and 76%, respectively) of the avian c-myc proto-oncogene were specifically amplified from cloned and genomic DNA. This method uses high-melting primers (Tm between 70 degrees and 74 degrees C), a two-step cycle that employs a 94 degrees C denaturation step and an annealing-elongation step between 70 degrees and 80 degrees C with or without formamide. PMID- 8457344 TI - DAF-amplified fragments can be used as markers for DNA from pulse field gels. AB - PCR-type amplification of genomic sequences using short, single and arbitrarily chosen primers (by DNA amplification fingerprinting [DAF]) was developed in our laboratory. Here we show that it is possible to produce specific fingerprints for subgenomic DNA fragments embedded in agarose, including fractions from conventional and pulse field gels. Fractions of restricted genomic DNA differing in mobility by only 2-3 mm gave one to three different products with different single primers. Yeast chromosome specific markers were easily produced and cloned. We also used DAF to generate specific amplification products of DNA cloned into a yeast artificial chromosome. These products were readily cloned into a plasmid vector. PMID- 8457345 TI - Generation of bidirectional deletions using DNase I. AB - As a result of the sporadic success we have had with established deletion generating methods, a simpler and more reliable method was developed. This method that allows efficient and reliable recovery of deletion subclones is a simple modification of earlier DNase I protocols. We have found that the choice of linear double-stranded DNA substrates eliminates many of the problems associated with the earlier protocols. PMID- 8457346 TI - Transgenic embryo yield is increased by a simple, inexpensive micropipet treatment. AB - A method for the treatment of micropipet tips for injection of DNA into pronuclei of mouse embryos is described. The method requires only standard laboratory equipment, a magnetic stirrer and an inexpensive commercially available grinding powder. The method involves little extra time and no special skills. After introduction of the method, the time required for injections was reduced by about 30%, and the yield of surviving embryos was increased by 28%. PMID- 8457347 TI - SPOT: an improved differential screening protocol that allows the detection of marginally induced mRNAs. AB - We have developed a differential screening technique, single plate one transfer (SPOT), that allows the easy detection of mRNAs induced only 2-fold to 3-fold or less above background. As a model system, we looked at the induction of mRNA by parathyroid hormone (PTH) in ROS 17/2.8 rat osteosarcoma cells. The basis for this technique is to symmetrically spot in quadruplicate, on a single plate, a large number of potentially positive plaques obtained from a primary, conventional screen. We then do only one transfer from this plate in order that there will be minimal variability in DNA transfer. This filter is cut into symmetrical strips so that all clones are multiply represented on each strip. These strips are then hybridized with different probes. Since each strip contains an approximately identical amount of DNA per plaque, it is possible to accurately detect mRNAs that are induced only slightly above background. Additionally, the large sizes of the DNA plaques, as well as spotting each clone serially, contribute to the sensitivity of the technique. PMID- 8457349 TI - A safe method for handling sequencing gels. PMID- 8457348 TI - An efficient method for the recovery of 14C in labeling experiments using wheat. AB - This report describes a reliable method of 14CO2 recovery from 14C-labeled sucrose applied to leaves of young wheat plants. After completion of the labeling experiment, sections of the plant are harvested, digested in concentrated sulfuric acid and oxidized by 3% hydrogen peroxide in a closed system containing CO2-absorbing 2 N NaOH. Heating the sulfuric acid containing vial to 85 degrees C is necessary to achieve near total recovery of 14C-label within 30 min. This technique can be applied to other plant or animal systems, to study the translocation of organic 14C-label. PMID- 8457350 TI - Solid-phase gene assembly of constructs derived from the Plasmodium falciparum malaria blood-stage antigen Ag332. AB - A general method for solid-phase gene assembly on streptavidin-coated magnetic beads has been developed. The introduction of biotin in the 5'-end of the initiation oligonucleotide enables anchoring to the bead by means of the streptavidin-biotin interaction. The immobilization of one oligonucleotide enables controlled, stepwise annealing/ligation of successive 5'-phosphorylated oligonucleotides to rapidly build up predesigned gene constructs. In this report, we have assembled gene constructs of different lengths derived from the Plasmodium falciparum malaria blood-stage antigen Ag332. The encoded gene products were subsequently expressed in Escherichia coli using two parallel expression systems based on staphylococcal protein A and streptococcal protein G, respectively. PMID- 8457351 TI - Specific and quantitative immunoprecipitation of tropomyosin and other cytoskeletal proteins by magnetic separation. AB - Immunoprecipitation is a powerful technique for purifying many proteins for which specific antibodies exist. Magnetic separation has recently been demonstrated to be effective in the immunoprecipitation of cell-surface proteins. We have used magnetic separation with anti-immunoglobulin or protein A bound to magnetic particles to immunoprecipitate labeled muscle tropomyosin and several other cytoskeletal proteins for which specific antibodies exist. We have not found it necessary to bind antigen-specific antibody to the magnetic particles, increasing the versatility of the technique. The quantitative recovery of tropomyosin from muscle cultures using magnetic separation is superior to Staph A (protein A positive Staphylococcus aureus cells). The specificity of magnetic separation also compares favorably with Staph A for immunoprecipitation of muscle tropomyosin. Fibroblast tropomyosin, vimentin (from muscle and osteoblast) and myosin heavy chain are other cytoskeletal proteins that are easily recovered with magnetic separation. Magnetic separation, therefore, appears to be a valuable technique for the immunoprecipitation of cytoskeletal proteins from various cell types. PMID- 8457352 TI - Sequence length and error analysis of Sequenase and automated Taq cycle sequencing methods. AB - We have examined DNA sequence error as a function of length using both a manual method of performing reactions with Sequenase and an automated Taq cycle sequencing method. DNA fragments from both methods were separated and analyzed on a sequencer. To determine the sequence of a cosmid insert (35.3 kb), 379 sequences were obtained from a manual Sequenase method, and 354 sequences were obtained from a Taq cycle sequencing method as performed on an automated robotic workstation and sequenced on an automated fluorescent sequencer. A highly redundant consensus of these sequences was obtained and aligned with the individual sequences to determine sequence error over the length of each sequence. The results of this study indicate that error is about 1% per position over the first 350 nucleotides, but increases thereafter to about 17% at 500 nucleotides. This pattern of accuracy was nearly equivalent for manual Sequenase methods and automated Taq cycle sequencing methods. The potential of these methods in large-scale DNA sequencing projects is discussed. PMID- 8457353 TI - A PCR-based strategy for extensive mutagenesis of a target DNA sequence. AB - A mixed population of mutagenic oligonucleotide primers was used to generate a set of point mutations in a short region of a retroviral gene by PCR amplification. The mixed population of mutagenic primers was generated by incorporating a mixture of A, G, C and T at specific sites during oligonucleotide synthesis. With the proportions of mutagenic nucleotides used for our experiments, 47 percent of the 213 clones analyzed had one or more point mutation in the target DNA sequence. In addition, unpredicted mutations were observed that contributed to the mutagenic complexity of the population. We have found this approach to be an efficient means for extensive mutagenesis of a defined target DNA sequence. PMID- 8457354 TI - Improved design of riboprobes from pBluescript and related vectors for in situ hybridization. AB - The pBluescript family of plasmids and phagemids are sophisticated multi-purpose cloning vectors that allow convenient production of single-stranded sense and anti-sense RNA probes corresponding to DNA sequences inserted into a large multiple cloning site array. We have observed that in many applications sense (control) probes generated from genes cloned into pBluescript II KS(-) give high background signals on in situ hybridization to human tissue sections. Our studies indicate that this spurious hybridization is due to sequences contained within both strands of the multiple cloning site between the SmaI and SacI sites that are similar to human 28S rRNA. This information is useful in construct design in order to minimize nonspecific background problems, as demonstrated by in situ hybridization of sense and anti-sense probes corresponding to a portion of human stromelysin-3 to sections of human lung carcinoma. PMID- 8457355 TI - Monitoring coupling of peptides to carrier proteins using biotinylated peptide. AB - The amount of synthetic peptide coupled to a carrier protein is a critical parameter in production of antipeptide antibodies. In the method described, biotinylated peptide was included as a tracer to monitor the coupling of peptide to keyhole limpet hemocyanin or BSA. The extent of coupling was assessed by first fractionating free and coupled peptide by gel filtration, then slot blotting an aliquot of each fraction onto nitrocellulose. The biotinylated peptide was detected using an avidin-horseradish peroxidase conjugate. To estimate the mass of peptide incorporated, the fractions were analyzed using a competitive ELISA. The limit of detection of this assay was < 0.1 pmol and was linear to 2 pmol. The mass of biotinylated peptide in each column fraction was determined using this assay and the total mass of peptide coupled to the carrier was calculated. Using these techniques, biotin-labeling provided a sensitive and versatile means to assess the quality of peptide-carrier protein conjugates. PMID- 8457356 TI - Comparison of the use of a dry chemistry analyser in primary care in Norway and the United Kingdom. AB - The results of a quality assessment survey of the most commonly used dry chemistry instrument in primary care in Norway and the United Kingdom, the Reflotron (Boehringer), are reported including an evaluation of some of the operational characteristics of the Reflotron users. The primary care users in Norway taking part in the study comprised 95 occupational health care departments and 89 general practices. In the UK, primary care users taking part were 95 occupational health care departments and 37 general practices. In terms of both accuracy and precision evaluation of concentrations of bilirubin, cholesterol, gamma-glutamyl transferase, glucose, triglycerides, urea and uric acid by primary care users was similar in the two countries, and to that of 60 Norwegian laboratories. Examination of operational characteristics revealed a lack of effective quality control measures in both countries, and some differences in the pattern of usage between primary care users in Norway and the UK, especially in general practice. The result of Reflotron tests were ready before the patient left in a considerably higher proportion of general practices in the UK than in Norway. It is concluded that the Reflotron is suitable for primary care use, but good, routine quality of analysis must be ensured through collaboration between primary care users and clinical chemists. PMID- 8457357 TI - Study of 500 patients attending an osteopathic practice. AB - The experiences of 500 consecutive patients presenting with a new episode of illness at a five practitioner osteopathic practice in an east midlands town is reported. The osteopath completed a structured questionnaire about each patient who then completed two symptom questionnaires, one before treatment and a second four months later. Questionnaires were completed by osteopaths for 495 patients (99.0%). Almost all patients completed the first questionnaire (98.6%) and 367 patients (73.4%) completed the second questionnaire. Female patients had more treatment sessions than male patients (3.2 versus 2.7 over the four month period, P < 0.01) and suffered from more spinal muscular problems and postural imbalance than males (P < 0.05). The commonest diagnostic group was spinal joint sprain and patients with this diagnosis reported significantly better symptom improvement at four months than those in other diagnostic groups. Greater improvement at four months was also associated with shorter duration of illness before treatment (P < 0.001). The 147 patients who had seen their general practitioner before attending the osteopath had worse symptoms of a longer duration than the 347 patients who had not seen their general practitioner (P < 0.001), but showed greater improvement in symptoms over the subsequent four months. It is concluded that suitable patients should be encouraged to attend an osteopath early on in an illness. In subsequent episodes, if osteopathic treatment is of benefit to them, patients should attend before they see their general practitioner. PMID- 8457358 TI - Postgraduate education allowance: educational attainment of subscribers and non subscribers to a centrally organized educational scheme. AB - The educational attainment of general practitioners in the west of Scotland region who subscribed to a centrally organized educational scheme for the postgraduate education allowance was compared with that of their colleagues who did not subscribe to the scheme. During the year studied (1990-91) 1712 of the 1830 principals in general practice in the region had sufficient sessions to claim their postgraduate education allowance. Of these 1712 doctors the 1353 who subscribed to the educational scheme attended a mean of 15.7 educational half day sessions during the study year in comparison with a mean of 12.5 half days attended by the 359 doctors who did not subscribe to the scheme. This difference was observed in all three categories of education--disease management, service management and health promotion--and was greatest in health promotion where subscribers attended a mean of 4.7 half days and non-subscribers 3.1. The doctors who were members of the scheme had achieved a better balance of education. A higher number had attended an educational day in each of the three categories, with the increase being 10.5% for subscribers versus non-subscribers for disease management, 20.0% for service management and 39.1% for health promotion. The differences between the two groups were greater for combinations of categories and 66.6% of subscribers had attended an educational day in each of the three categories compared with 40.9% of non-subscribers. A centrally organized educational scheme for a region can give a balanced spread of education and is likely to meet the educational requirements of the new contract for general practitioners. PMID- 8457359 TI - Rationale behind the General Medical Council's proposed new procedure for the assessment of doctors' performance. PMID- 8457360 TI - Evaluation of the diagnostic value of pneumatic otoscopy in primary care using the results of tympanometry as a reference standard. AB - The aim of this study was to determine the value of pneumatic otoscopy in diagnosing otitis media with effusion in primary care. Pneumatic otoscopy was carried out for 111 children aged one to 16 years and the results obtained compared with those obtained from tympanometry. The children were those who had attended for a regular ear, nose and throat check up in the health centre of a school for the deaf during the period November 1989 to January 1990. Pneumatic otoscopy and tympanometry with the GSI 28 instrument (Grason-Stadler) were carried out by a trained ear, nose and throat nurse. All relevant features determined using otoscopy--the colour, position and mobility of the tympanum--and an overall assessment were recorded. The results of tympanometry were evaluated independently of the otoscopic findings. In the population examined the predictive values of positive and negative results of pneumatic otoscopy for diagnosing effusion were high; the sensitivity was low. Serious retraction of the eardrum and absence of mobility under positive pressure were the most predictive features but the colour of the tympanum did not show any relation to effusion. In the youngest age group (one to five years) 56% of the children had abnormal otoscopic findings in either one or both ears (odds ratio for this group versus remaining children 3.75; 95% confidence interval (CI) 1.75 to 15.2). The odds ratios of past and present history of upper respiratory tract infection with respect to abnormal results from otoscopy were 2.41 (95% CI 1.05 to 5.53) and 2.95 (95% CI 1.17 to 7.45), respectively. Pneumatic otoscopy carried out by an experienced health care worker is of high diagnostic value when compared with the results of tympanometry. Pneumatic otoscopy can improve the diagnostic capabilities of general practitioners and other primary care workers with regard to otitis media with effusion. PMID- 8457361 TI - Attitudes towards practice nurses--survey of a sample of general practitioners in England and Wales. AB - Practice nursing has expanded rapidly since the 1990 contract for general practitioners. In 1990, a national survey was undertaken of the attitudes of a random sample of general practitioners towards practice nurses. Responses to the postal questionnaire were received from 41.9% of the 4800 general practitioners sampled. Of the responding general practitioners, 90.0% were satisfied with the role of the practice nurse within their practice. To fulfil the requirements of the 1990 contract for general practitioners 50.7% had created a new nursing post, and 83.1% had expanded the role of nurses already employed; 89.7% wished to see further expansion of the practice nurse's role. However, lack of space was the factor most frequently reported as limiting the expansion of the practice nurse's role, mentioned by 76.0% of general practitioners. Only 43.7% of general practitioners recognized lack of opportunities for practice nurse training as a hindrance to role expansion. The key to managing the expansion of the role of the practice nurse lies in the provision of resources and in training. A pressing need exists for a national training scheme based in general practice. PMID- 8457362 TI - Psychiatric morbidity in children and adolescents: a suitable cause for concern. PMID- 8457363 TI - The scar that is more than skin deep: the stigma of depression. AB - The stigma of depression is a major factor hindering effective treatment. In 1992, the Royal College of Psychiatrists and the Royal College of General Practitioners launched a 'defeat depression' campaign. This aimed to reduce the stigma associated with depression by improving public awareness of the condition and by improving health professionals' knowledge of the illness. The mental health team and general practitioners can work together to encourage people to seek help to alleviate this distressing illness. PMID- 8457364 TI - The doctor with an inherited defect of colour vision: effect on clinical skills. PMID- 8457365 TI - Use of benzodiazepines. PMID- 8457366 TI - Diagnosis of hypertension. PMID- 8457367 TI - Yellow card reporting. PMID- 8457368 TI - Sex differences in morbidity in children. PMID- 8457369 TI - Comparison of peak flow meters. PMID- 8457370 TI - Mental health care. PMID- 8457371 TI - Nitrite test for bacteriuria detection. PMID- 8457372 TI - Mental health care. PMID- 8457373 TI - Continuing medical education. PMID- 8457374 TI - Cervical cytology. PMID- 8457375 TI - Value of paediatric surveillance. PMID- 8457376 TI - Psychiatric morbidity among children who are frequent attenders in general practice. AB - This two-part cross-sectional study set out to determine the frequency and nature of psychiatric disorder among children aged seven to 12 years who were frequent attenders at one of two general practices. The first part of the study was an interview survey with a sample of 109 children who attended frequently (four or more times in one year) and 23 children who had not attended in one year. Descriptive information from a structured parental interview was used to diagnose childhood psychiatric disorder. The second part of the study was a postal survey with a sample of 194 children selected independently of frequency of attendance. The children's score on a parental screening questionnaire was used to determine probable psychiatric disorder. The response rates were 78% and 75% for the interview and postal studies, respectively. Of the children aged seven to 12 years registered with the two practices 21% were found to be frequent attenders. Attendances by frequent attenders accounted for 51% of all attendances in this age group. Psychiatric disorder was more common among frequent attenders than non attenders (29% versus 9%, P < 0.05). Most of the psychiatric disorders were of an emotional nature (63%). The postal survey revealed that 15% of the children in this age group had a probable psychiatric disorder. It can therefore be estimated that 40% of children in the population with psychiatric disorder were frequent attenders.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457377 TI - Nucleotide sequence analysis of HTLV-I isolated from cerebrospinal fluid of a patient with TSP/HAM: comparison to other HTLV-I isolates. AB - Human T-cell leukemia virus type I (HTLV-I) has been associated with adult T-cell leukemia/lymphoma and the chronic neurologic disorder tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). To study the genetic structure of the virus associated with TSP/HAM, we have obtained and sequenced a partial genomic clone from an HTLV-I-positive cell line established from cerebrospinal fluid (CSF) of a Jamaican patient with TSP/HAM. This clone consisted of a 4.3-kb viral sequence containing the 5' long terminal repeat (LTR), gag, and N-terminal portion of the pol gene, with an overall 1.3% sequence variation resulting from mostly nucleotide substitutions, as compared to the prototype HTLV-I ATK-1. The gag and pol regions showed only 1.4% and 1.2% nucleotide variations, respectively. However, the U3 region of the LTR showed the highest sequence variation (3.6%), where several changes appear to be common among certain TSP/HAM isolates. Several of these changes reside within the 21-bp boundaries and the Tax-responsive element. It would be important to determine if the observed changes are sufficient to cause neurologic disorders similar to the murine leukemia virus system or simply reflect the divergent pool of HTLV-I from different geographic locations. At this time, we cannot rule out the possibility that the observed changes have either direct or indirect significance for the HTLV-I pathogenesis in TSP/HAM. PMID- 8457378 TI - Isolation of a cDNA clone encoding DNA-binding protein (TAXREB107) that binds specifically to domain C of the tax-responsive enhancer element in the long terminal repeat of human T-cell leukemia virus type I. AB - Five cDNA clones for TAXREB proteins that bind to the tax-responsive enhancer element of human T-cell leukemia virus type I (HTLV-I) were isolated from a Jurkat cell cDNA library. The beta-galactosidase fusion proteins of three of these clones specifically recognized the domain C within the enhancer. One of the three cDNAs, encoding TAXREB107, contained an open reading frame with 288 amino acid residues. RNA blot analysis showed that the level of mRNA for TAXREB107 increased transiently in Jurkat cells on treatment with TPA. Immunoblot analysis showed that polyclonal antibody against TAXREB107 specifically recognized a 34-kD protein in Jurkat cells. TAXREB107 may participate in tax-mediated trans activation of transcription. PMID- 8457379 TI - HTLV-II infection in Florida Indians. AB - A significantly increased prevalence of antibodies to human T-cell leukemia virus (HTLV) has been described in several native American populations in the United States and Latin America. Initial virologic studies indicate that HTLV-II is the predominant virus responsible for this antibody pattern. We obtained blood samples from 106 Seminole Indians living on four reservations in Southern Florida. Seropositivity to HTLV-I/II was found in 14 (13.2%) of these individuals. Polymerase chain reaction (PCR) documented HTLV-II and the absence of HTLV-I in 7 of the 9 donors available for follow-up testing of white blood cells. Evaluation of various risk factors excluded blood transfusion or intravenous drug use as an important contributing factor to the HTLV-II seroprevalence rate. These studies support the hypothesis that HTLV-II is endemic in many native American tribes in the Western hemisphere. PMID- 8457380 TI - Simian immunodeficiency virus (mac 251-32H) transmembrane protein sequence remains conserved throughout the course of infection in macaques. AB - Two cynomolgus macaques were infected with a genetically complex challenge stock of simian immunodeficiency virus (SIVmac251-32H). The polymerase chain reaction (PCR) was used to amplify the env gp41, rev, and nef overlapping coding sequences from provirus present in the blood of both animals at 1, 6, and 15 months post infection (p.i.). The predominant, env sequences found in both animals at the three time points were very similar to that found in the original 11/88 challenge stock. The functionally important hydrophobic fusion and membrane-spanning domains within gp41 remained conserved throughout the course of infection. Nucleotide variation within the region corresponding to the REV response element (RRE) was limited to four positions, none of which were predicted to cause any significant disruption to the secondary structure of the RRE. Very little genetic variation was observed in and around the cluster of potential glycosylation sites of the external portion of gp41. However, the existence of a previously assigned variable region elsewhere in the cytoplasmic domain of gp41 was confirmed. The three gene loci (env, rev, and nef) examined varied independently. All changes in the predominant protein sequences were brought about by single nucleotide substitutions only. After 15 months of infection with SIV, 1 animal was sick from SIV-induced disease whereas the other remained healthy. In-frame stop codons within the transmembrane protein occurred with a much greater frequency in the healthy animal. PMID- 8457381 TI - Evaluation of testing algorithms following the use of combination HIV-1/HIV-2 EIA for screening purposes. AB - The licensure of combination human immunodeficiency virus type 1 and type 2 (HIV 1/HIV-2) enzyme immunoassays (EIAs) by the Food and Drug Administration has been accompanied by a recommendation that U.S. blood banks begin testing the nation's blood supply for HIV-2 by June 1, 1992. The performance of a recently licensed combination HIV-1/HIV-2 EIA (Genetic Systems) was evaluated using 3100 sera collected in the United States. A total of 2,049 sera were obtained from populations with low risk for HIV infections, and 1,051 sera from populations with high-risk behaviors. The combination EIA, in comparison with monospecific EIA, was found to be 100% sensitive for HIV-1 for both populations. The high-risk population had an HIV-1 seroprevalence rate of 17.4%, with a positive predictive value (PPV) of 97.3%. The low-risk population had an HIV-1 seroprevalence of 0.05% with a PPV of 8%. The incorporation of the combination EIA in various testing algorithms was also evaluated, and recommendations are given with consideration for the type of screening and populations involved. PMID- 8457382 TI - Diversification of HIV-1 strains after infection from a unique source. AB - In 1990, 7 hemophilia B patients were infected with human immunodeficiency virus type 1 (HIV-1) after exposure to a single common lot of clotting factor. The hypervariable regions V1 and V2 of the proviral env gene from the patients shared a homology between 97.5% and 100% at the time of seroconversion. To determine the in vivo diversification of these epidemiologically closely related virus strains, the patients were followed up in the early phase of HIV infection. Direct sequencing of the V1/V2 region in the env gene still revealed a very high degree of homology (96.5%-100%). In the case of the patient who showed the highest decrease of CD4+ cells, moderate genetic diversification of the virus was associated with a biological differentiation. The strain originally presenting two expressed substitutions displayed three more deviations 9 months after the first investigation (including one reversion to the consensus sequence). In addition, the virus that originally could not be cultivated could now be isolated as a low cytopathogenic agent. This study provides evidence that the high genetic homogeneity of HIV-1 observed at the time of seroconversion is maintained as a predominant consensus sequence in the following so-called latent phase of infection. PMID- 8457383 TI - Effect of mutations in the V3 loop of HIV-1 gp120 on infectivity and susceptibility to proteolytic cleavage. AB - It has been suggested that the V3 domain of human immunodeficiency virus type 1 (HIV-1) isolates has to interact with a cell-surface-associated or endosomal proteinase during virus entry into susceptible cells. To investigate this hypothesis, we examined the effect of several mutations in the V3 loop on its susceptibility to proteolytic cleavage by thrombin and cathepsin E and compared it with the effect of these mutations on viral infectivity. The data obtained indicate that, if an interaction between the V3 loop and a proteinase is indeed crucial for viral entry, the substrate requirements for such a proteinase(s) would have to be very complex. In particular, it seems unlikely that a single enzyme with a unique specificity would be able to interact with all of the different HIV-1 and HIV-2/SIV strains isolated so far. Therefore, one would have to postulate the involvement of several cellular proteinases, or proteases with multiple specificities, in V3-based viral tropism. PMID- 8457384 TI - The galactosyl ceramide/sulfatide receptor binding region of HIV-1 gp120 maps to amino acids 206-275. AB - Our recent studies have indicated that galactosyl ceramide (GalCer) or sulfatide (sul) may serve as an alternate receptor for human immunodeficiency virus (HIV) in neural cells. In this paper, we describe the mapping of GalCer/sul binding region of HIV env glycoprotein gp120. Deglycosylated gp120 binds to GalCer, suggesting that the amino acids of glycoprotein gp120 and not the carbohydrates are responsible for the observed binding. Specific regions of gp120 responsible for the binding were analyzed by using varying-length truncations of gp120 expressed in Escherichia coli and vaccinia virus. Purified recombinant gp120 containing amino acids 200-295 of gp120 bind to GalCer/sul, whereas recombinant env proteins that deleted this region did not bind. These recombinant proteins also bind to SK-N-MC-derived neuroblastoma cells, the binding of which is inhibited by anti-GalCer. In addition, 125I-labeled gp120 binding to GalCer is inhibited by these proteins. Studies using lysates containing truncated gp120 expressed in vaccinia virus also gave similar results. By eliminating the overlapping regions that do not bind, we conclude that the amino acids responsible for GalCer/sul binding reside between amino acids 206 and 275. The significance of this mapping is discussed in relation to the neurotropism of HIV. PMID- 8457385 TI - High levels of 2',5'-oligoadenylate synthetase and 2',5'-oligoadenylate-dependent endonuclease in human trophoblast. AB - Human placenta contains a high level of 2',5'-oligoadenylate (2-5A) synthetase activity of the 100-kD form of the enzyme. About 20% of the placental 2-5A synthetase activity was found to be cytosolic, whereas the remaining 80% was released by 0.5 M KCl in the presence of detergent. Most of the enzyme activity was localized in trophoblast cells, which also contain a high level of 2-5A dependent RNase L activity. The purified trophoblast 100-kD 2-5A synthetase was shown to be activated by human immunodeficiency virus type 1 (HIV-1) 5' RNA 1-311 and 1-707, which both contain the TAR and primer binding site (PBS) structured regions. These two HIV-1 RNAs activated human trophoblast 2-5A synthetase at the same level as poly(I).poly (C), a standard highly efficient activator of the enzyme, and at the same optimal concentration. On the contrary, HIV-1 RNA 311 618, a poorly structured region missing TAR and PBS, was shown to be a poor activator of the enzyme. The specific cellular location of the 2-5A synthetase and its efficient activation by HIV 5' RNA favors the idea that the trophoblast 2 5A system negatively controls HIV replication in trophoblasts. PMID- 8457386 TI - Research on coronary disease in women: political or scientific imperative? PMID- 8457387 TI - Experience of cardioverter-defibrillators inserted without thoracotomy: evaluation of transvenously inserted intracardiac leads alone or with a subcutaneous axillary patch. AB - OBJECTIVES: To compare the efficacy of a purely transvenous cardioverter defibrillator (ICD) system with that of a system with a supplementary subcutaneous patch. To evaluate clinical follow up of these lead arrangements that do not require thoracotomy. DESIGN: A simplified defibrillation protocol to test two different lead arrangements during implantation, with routine clinical follow up after implantation. SETTING: Tertiary referral centre for treatment of arrhythmia. PATIENTS: 22 consecutive patients selected for implantation of an ICD because of life-threatening ventricular arrhythmias (ventricular fibrillation or sustained ventricular tachycardia) of whom 20 entered the test protocol. INTERVENTION: Implantation of an ICD with transvenously inserted intracardiac leads and a subcutaneous patch and assessment of effective defibrillation followed by testing of the purely transvenous approach. MAIN OUTCOME MEASURES: Reproducible conversion of ventricular fibrillation to sinus rhythm at a certain energy level, providing a safety margin of at least 10 J for both lead arrangements. Confirmation of efficacy during clinical follow up (mean 6 months). RESULTS: A transvenous lead system combined with a subcutaneous axillary patch was implanted in 20/22 patients and it provided adequate and acceptable energy levels. In 10/20 tested patients a purely transvenous lead configuration provided an acceptable safety margin as well. Nine patients had clinical recurrences: all these arrhythmias were successfully converted. CONCLUSION: A transvenous lead system was sufficient in 50% of the patients at the time of implantation. Data on long-term clinical follow up of this arrangement are not available. The approach without thoracotomy with a subcutaneous patch is feasible and effective in most patients selected for ICD treatment. PMID- 8457388 TI - Clinical significance of rapid ventricular tachycardia (> 270 beats per minute) provoked at programmed stimulation in patients without confirmed rapid ventricular arrhythmias. AB - Rapid uniform ventricular tachycardia (VT) (> 270 beats/min) or ventricular flutter induced during electrophysiological studies is thought not to be clinically significant in patients without cardiac arrest or documented rapid VT. The purpose of the study was to follow up 73 patients with inducible ventricular flutter but without confirmed rapid spontaneous VT. A long follow up (mean 3.5 years) identified two groups of patients. The first group had an excellent outcome and was characterised by a normal 24 hour Holter monitoring. In the second group, however, the risk of cardiac mortality was high (35%) and spontaneous VT was < 270 beats/min (26%) and was characterised by couplets or salvos of extrasystoles on Holter monitoring. In this group the history of syncope and decreased left ejection fraction increased the risk of mortality and VT. The presence of late potentials increased the risk of spontaneous VT. Electrophysiologically guided antiarrhythmic therapy reduced the risk of VT. Ventricular flutter was a non-specific finding in patients with normal Holter monitoring. In contrast, in patients with salvos of extrasystoles, ventricular flutter was associated with a high risk of cardiac mortality and VT. PMID- 8457389 TI - Apolipoprotein (a) concentrations and susceptibility to coronary artery disease in patients with peripheral vascular disease. AB - OBJECTIVE: To investigate the relation between apolipoprotein(a) concentrations and angiographically defined coronary artery disease in patients with atheromatous peripheral vascular disease. DESIGN: 40 consecutive patients were recruited at the time of admission for peripheral vascular surgery. All underwent clinical assessment and coronary arteriography. Apolipoprotein(a) concentrations were measured by an immunoradiometric assay. SETTING: Tertiary referral centre. SUBJECTS: Patients requiring surgical intervention for large vessel peripheral vascular disease. MAIN OUTCOME MEASURES: Presence or absence and severity and distribution of angiographically defined coronary artery disease. Measurement of circulating contractions of apolipoprotein(a) and other lipid indices. RESULTS: Coronary artery disease was absent in 11 patients (group 1), mild to moderate in 12 (group 2), and severe in 17 (group 3). The distribution of peripheral vascular disease and of standard lipid indices was similar in these three groups of patients. There was a significant difference in apolipoprotein(a) concentrations between the three groups, with concentrations progressively increasing with the severity of coronary artery disease (mean (95% confidence interval): group 1, 112 U/1 (52 to 242); group 2, 214 U/1 (129 to 355); group 3, 537 U/1 (271 to 1064) (analysis of variance p < 0.005). The prevalence of coronary artery disease was increased 7.4 fold in patients with apolipoprotein(a) concentrations that were greater than the cohort median (206 U/1) (p < 0.01). CONCLUSIONS: The results show an association between apolipoprotein(a) concentrations and angiographically defined coronary artery disease in patients with large vessel peripheral vascular disease. The findings imply differences in the pathogenesis of coronary and peripheral atheroma and suggest that the measurement of apolipoprotein(a) may prove a useful additional tool in the risk factor assessment of patients undergoing peripheral vascular surgery. PMID- 8457390 TI - Hypoxia and the heart. PMID- 8457391 TI - Increased left atrial chamber stiffness in hypertrophic cardiomyopathy. AB - OBJECTIVE: To investigate left atrial chamber stiffness and its influence on left atrial and left ventricular functions in hypertrophic cardiomyopathy. DESIGN: Prospective study. SETTING: Department of internal medicine in a university teaching hospital. PATIENTS: Five control subjects, six patients with essential hypertension, and 11 patients with hypertrophic cardiomyopathy. INTERVENTIONS: Measurement of left atrial pressure by a tip micromanometer and of real-time left atrial volume from left atrial cineangiograms. MAIN OUTCOME MEASURE: Left atrial stiffness constant determined by fitting the ascending limb of the v loop of the left atrial pressure-volume relation to an exponential curve. RESULTS: The mean (SD) left atrial chamber stiffness constant was significantly larger in patients with hypertrophic cardiomyopathy than in controls (0.063 (0.018) v 0.041 (0.006), p < 0.05) and was correlated with left ventricular wall thickness (r = 0.560, p < 0.01). Left atrial reservoir volume (left atrial emptying volume before atrial contraction) was significantly smaller in patients with hypertrophic cardiomyopathy than in the controls (7.3 (2.1) v 12.5 (4.4) ml/m2, p < 0.01) and was inversely correlated with the left atrial chamber stiffness constant (r = 0.598, p < 0.01). The cardiac index was inversely correlated with the left atrial chamber stiffness constant (r = -0.542, p < 0.01). CONCLUSIONS: Left atrial chamber stiffness was increased in patients with hypertrophic cardiomyopathy and this affected the left atrial reservoir function. This may in turn have affected cardiac output. PMID- 8457392 TI - Balloon angioplasty of adult aortic coarctation. AB - OBJECTIVE: To examine the use of balloon angioplasty in the treatment of native adult aortic coarctation. DESIGN: Haemodynamic and angiographic studies to establish the diagnosis of aortic coarctation were established before carrying out the procedure in all patients. SETTING: All the studies and angiographic procedures were performed in a large district general hospital within the departments of cardiology and radiology. There was careful perioperative monitoring. The mean hospital stay was three days. PATIENTS: 15 adult patients (with clinical, haemodynamic, and angiographic evidence of native aortic coarctation) were considered for this treatment. 13 were offered balloon angioplasty. One was excluded, as there was no significant gradient across the lesion. One patient had complete atresia at the site of the coarctation. INTERVENTIONS: Percutaneous transluminal balloon angioplasty was carried out with balloon catheters diameter 2 mm less than the diameter of the aorta immediately below the left subclavian artery to minimise the possibility of tearing the aortic wall. MAIN OUTCOME MEASURES: Abolition or significant reduction of the preoperative gradient was achieved in all 13 patients treated. Reduction in blood pressure of the upper limb was also achieved in all of the patients. Only four patients required continued antihypertensive treatment. Two patients developed false aneurysms after the procedure and required surgery. No deaths occurred. These results compare favourably with conventional surgery and are much more economical. CONCLUSIONS: Balloon angioplasty could become the first line treatment for all patients with native adult aortic coarctation, but longer term follow up is required to validate this. PMID- 8457393 TI - Pulsed Doppler echocardiographic assessment of portal venous flow patterns in patients after the Fontan operation. AB - OBJECTIVE: To assess the effect of the condition of the right heart after the Fontan operation on portal venous flow, and to determine whether the characteristics of portal venous flow were different when there was an atriopulmonary connection with atrial septal closure rather than an atriopulmonary or total cavopulmonary connection with intra-atrial routing. PATIENTS AND METHODS: After the Fontan operation six patients with an atriopulmonary connection (group 1), three patients with an atriosubpulmonary connection (group 2), four patients with intra-atrial routing and an atriopulmonary connection (group 3), and five patients with a total cavopulmonary connection (group 4) were studied by pulsed Doppler echocardiography. The flow signals were recorded for the pulmonary artery, hepatic vein, and intrahepatic portal vein in each patient. Postoperative cardiac catheterisation was performed in 16 of the 18 patients. The Doppler findings were compared with those of 14 controls. RESULTS: The portal flow was pulsatile in 13 patients and constant in five patients. Reversed flow was shown at or just after the QRS wave after hepatic venous regurgitation in two group 1 patients. The flow signal was interrupted in two group 1 patients and two group 2 patients. Decrease in velocity of flow was recorded in two group 1 patients, one group 2 patients, three group 3 patients, and one group 4 patient. Portal flow was constant in one group 3 patient and four group 4 patients. The pulsatility ratio ranged from 0.46 to 0.49 (mean (SD), 0.03 (0.32)) in the patients from group 1 and 2, from 0.41 to 0.76 (0.54 (0.15)) in group 3, and from 0.70 to 0.80 (0.75 (0.04)) in group 4. The ratio in the controls ranged from 0.29 to 0.83 (0.61 (0.13)). The ratio was significantly lower in groups 1 and 2 than in group 3 (p < 0.01), group 4 (p < 0.01), or the controls (p < 0.005). There was no significant difference in the ratio between group 3 and group 4 and no correlation between the pulsatility ratio and the cardiac index (r = 0.26), mean right atrial pressure (r = 0.25), or pulmonary vascular resistance (r = 0.17). CONCLUSION: The larger hepatic venous regurgitation caused by atrial contraction in patients with an atriopulmonary connection correlated with the higher portal pulsatility and a total cavopulmonary connection reduced portal pulsatility. PMID- 8457394 TI - Novel uses of the Rashkind ductal umbrella in adults and children with congenital heart disease. AB - OBJECTIVE: To show possible alternative uses of the Rashkind ductal umbrella. DESIGN: Descriptive study of selected, non-randomised patients; with specific congenital heart lesions other than an arterial duct. SETTING: A tertiary referral centre. PATIENTS: Nine patients with congenital heart lesions; four with interatrial communications after a fenestrated Fontan procedure two with large aortopulmonary collaterals, three with an unoperated ventricular septal defect. INTERVENTIONS: Placement of a Rashkind umbrella occluder as treatment for a haemodynamically important lesion. RESULTS: Successful placement with symptomatic and haemodynamic improvement in all. CONCLUSIONS: The Rashkind ductal umbrella may be used successfully to treat some patients with aortopulmonary collateral vessels, ventricular septal defects, and interatrial communications after the fenestrated Fontan procedure. PMID- 8457395 TI - Morphological variations of fossa ovalis atrial septal defects (secundum): feasibility for transcutaneous closure with the clam-shell device. AB - OBJECTIVE--To assess the morphology of fossa ovalis atrial septal defects (FOASD; secundum atrial septal defect) to determine in what proportion percutaneous closure with the clam-shell device might be feasible. DESIGN--Review of the intraoperative description of the morphology and size of FOASD. PATIENTS--106 consecutive patients with FOASD. SETTING--A regional children's cardiac referral centre. MAIN OUTCOME MEASURES--Determination of morphology and size of FOASD. RESULTS--Morphological variations in the FOASD were found: (1) central FOASD, 70 (66%); (2) superior FOASD, 4 (3.7%); (3) inferior FOASD, 8 (7.6%); (4) posterior FOASD, 2 (1.9%); (5) subtotal absence of atrial septum, 3 (2.8%); (6) completely fenestrated FOASD, 10 (9.4%); (7) partially fenestrated FOASD, 9 (8.5%). Depending on its site, the edge of the FOASD may be close to important atrial structures such as the orifices of the superior and inferior caval veins, coronary sinus, and right pulmonary veins. The shape of the FOASD was usually oval with the major diameter ranging from 10 to 50 mm with a mean (SD) of 27.8 (0.93) mm. The minor diameter ranged from 4 to 30 mm with a mean (SD) of 15.3 (5.9) mm. The ratio of the major to minor diameter ranged from 1.0 to 5.0 with a mean of 2.01. Based on intraoperative measurement and description, it is postulated that it should be possible to close about 50% of these defects with the clam-shell device. PMID- 8457396 TI - Transcatheter closure of Blalock-Taussig shunts with a modified Rashkind umbrella delivery system. AB - Transcatheter occlusion of Blalock-Taussig shunts was successfully performed in three children with the Rashkind double umbrella occluding device. Complete occlusion was confirmed angiographically in two patients and echocardiographically in the third. The delivery system was adapted for use through smaller sheaths making it more suitable for small children or arterial access. PMID- 8457397 TI - Postoperative cardiac surgical care: an alternative approach . AB - Combined appropriate anaesthetic and surgical techniques have allowed increasing numbers of patients to be successfully managed in a general surgical recovery ward after cardiac surgery rather than in an intensive care unit. From 1983 to 1989, 933 of 1542 patients undergoing open heart surgery were transferred to the general surgical recovery ward in the immediate postoperative period. Of these, 718 (77%) had undergone coronary artery bypass grafts, sometimes combined with other procedures and 168 (18%) had had cardiac valve replacements with or without other procedures. The remaining 47 (5%) had had miscellaneous cardiac operations. Significant cardiac complications occurred in 29 (3%) patients. The 24 hour chest radiograph was reported as abnormal (mainly atelectasis and effusion) in 63% of patients. Most resolved spontaneously or with physiotherapy. Twenty nine (3%) patients were re-explored to achieve haemostasis. There were no deaths in the general surgical recovery ward. Thirty seven (4%) patients had to be transferred to the intensive care unit for various reasons. The remaining 896 patients were transferred to the general ward after one night (871 patients) or two nights (25 patients) in the general surgical recovery ward. The average duration of stay in hospital for these patients was 9.3 days. Because of the overall success of such management and the low rate of complications over 80% of patients are now managed in the general surgical recovery ward after open heart surgery. The resulting savings in capital expenditure of equipment, medical, nursing, and technical personnel are substantial, and there are major implications for the planning of new cardiothoracic units. PMID- 8457398 TI - Asymmetry of cardiac [123I] meta-iodobenzyl-guanidine scans in patients with ventricular tachycardia and a "clinically normal" heart. AB - OBJECTIVE: Patients with exercise induced ventricular tachycardia associated with a "clinically normal" heart may have an abnormality of the regional distribution of the cardiac sympathetic nerve supply. In this study the regional distribution of the myocardial nerve supply in patients with ventricular tachycardia (VT) and control subjects was examined by [123] meta-iodobenzylguanidine (MIBG) scanning. PATIENTS AND DESIGN: Eight patients with exercise induced VT and seven patients with VT unrelated to exercise with "clinically normal" hearts were studied and compared with a control group of six subjects with atrioventricular reentrant tachycardia not related to exercise and eight patients with angiographically normal left ventricular function and normal coronary anatomy who had thallium scans without evidence of ischaemia or fixed perfusion deficits. METHODS: Single photon emission computed tomography gamma scanning was performed in patients three hours after intravenous injection of MIBG. The left ventricular MIBG uptake data was processed into bull's-eye target plots. The inferior portion of the scan frequently showed artefact due to uptake of MIBG in the liver or spleen and was not used for statistical analysis. Asymmetry of uptake was defined as a ratio of uptake exceeding 1.25 in the upper quadrants (posterior (anterolateral free wall)/anterior (anteroseptal region)) of the MIBG scan. RESULTS: Patients with VT had a higher proportion of asymmetrical MIBG scans (47%) than subjects in the control groups (0%) and this was particularly obvious in the patients with exercise induced VT (62.5%). This suggests that patients with VT may have relative denervation in the septal portion of the left ventricle leading to an imbalance of the sympathetic supply to the myocardium and locally imbalanced sympathetic or parasympathetic interactions. Considerable evidence from animal experiments suggests that imbalance of the sympathetic supply to the myocardium is important in the genesis of ventricular arrhythmia. CONCLUSIONS: These results support the hypothesis that selective denervation of the human myocardium may be an important mechanism in the genesis of VT in "clinically normal" hearts. PMID- 8457399 TI - Coarctation of the aorta life and health 20-44 years after surgical repair. AB - OBJECTIVE: To examine the health and lifestyle of a group of patients who had repair of coarctation of the aorta 20-44 years ago (these were the first such operations in the United Kingdom) and to see how the results would influence current management strategies. DESIGN: Attempts were made to contact all patients by questionnaire. They were then requested to attend for a clinical examination. SETTING: Patients had their initial surgery at the Westminster Hospital (by Charles Drew) and the follow up examination at the same hospital. PATIENTS: 149 operations were performed. 70 of the 106 patients presumed to be alive were traced and 62 replied. 42 attended for examination. Only patients with the diagnosis of simple coarctation were included. Some patients had had coincidental ligation of a patent ductus arteriosus but none had any other cardiac abnormality requiring surgical or medical treatment. Those who died during the follow up period were described in paper by Bobby et al (Br Heart J 1991;65:271-6). MAIN OUTCOME MEASURES: Current symptoms and life situations, evidence of cardiac disease, further cardiac surgery, current and retrospective blood pressures, and Doppler echocardiographic examination. RESULTS: 29 (69%) had cardiovascular disorder. Doppler echocardiography did not show previously unrecognised major recoarctation. 19 (46%) had hypertension at follow up and there was evidence of enlargement of the aortic root or arch in seven (16%) patients, who tended to have had surgery at a later age. No evidence of cerebrovascular accident was found. CONCLUSIONS: In this group of patients with surgically repaired simple coarctation, late morbidity (particularly aortic aneurysm, aortic valve disease, and ischaemic heart disease) was common. The incidence of intracranial haemorrhage seemed to have been reduced by surgical repair. The integrity of the surgery remained good. Many patients did not have any regular cardiovascular review. Long-term anxiety related to early surgical experiences was evident. Even after apparently successful surgical repair of aortic coarctation. It would be prudent for all patients to have long-term review. PMID- 8457400 TI - Incidence and prognosis of congenital aortic valve stenosis in Liverpool (1960 1990). AB - OBJECTIVE: To determine the incidence and prognosis of congenital aortic valve stenosis in the five Health Districts of Liverpool that make up the Merseyside area. DESIGN: The records of the Liverpool Congenital Malformations Registry and the Royal Liverpool Children's Hospital identified 239 patients (155 male, 84 female) born with aortic valve stenosis between 1960 and 1990. Patients were traced to assess the severity of stenosis at follow up. Information on the severity at presentation and all subsequent events was obtained. RESULTS: Congenital aortic valve stenosis occurred in 5.7% of patients with congenital heart disease born in the Merseyside area. The median age at presentation was 16 months (range 0-20 years). Stenosis was mild at presentation in 145 patients, moderate in 33, severe in one and critical in 21 and 39 had a bicuspid valve without stenosis. Additional cardiac lesions were significantly more common in children presenting under one year of age and in those with critical stenosis. The median duration of follow up was 9.2 years (range 1-28 years) and seven patients were lost to follow up. 81 operations were performed in 60 patients. The reoperation rate was 28.3% after a median duration of 8.7 years (range 2.5-18 years). 15% of patients who presented with mild stenosis subsequently required operation compared with 67% of those with moderate stenosis. There were no sudden unexpected deaths and no deaths after aortic valvotomy, except in those presenting with critical stenosis. Mortality was 16.7% but patients presenting with critical aortic stenosis had a much worse prognosis. Actuarial and hazard analysis showed that the survival and absence of serious events (aortic valve surgery or balloon dilatation, endocarditis, or death) were significantly better in patients who presented with mild aortic stenosis than in those who presented with moderate aortic stenosis. 75% of patients presenting with mild stenosis had not progressed to moderate stenosis after 10 years of follow up. CONCLUSIONS: Congenital aortic valve stenosis may be progressive even when it is mild at presentation. Patients presenting with mild stenosis, however, have a significantly better prognosis than those presenting with moderate stenosis. An accurate clinical and echocardiographic assessment of the severity of aortic valve stenosis at presentation provides a good guide to prognosis into early adult life. PMID- 8457401 TI - Transcatheter stent implantation to treat aortic coarctation in infancy. AB - A ten week old girl who had previously undergone a palliative procedure for the hypoplastic left heart syndrome had unrelieved aortic coarctation that did not respond to standard balloon dilatation. Complete relief of coarctation with prompt clinical improvement was achieved with placement of an 8 mm self-expanding stent. Transcatheter stent implantation may have a role in selected patients with aortic coarctation. PMID- 8457402 TI - Implications for present and future applications of the implantable cardioverter defibrillator resulting from the use of a simple model of cost efficacy. AB - OBJECTIVE: To develop a model to assess the cost-efficacy of the implantable cardioverter defibrillator to prevent sudden death. The model must be sufficiently flexible to allow the use of cost and survival figures derived from different sources. SETTING: The study was conducted in a teaching hospital department of cardiology with experience of 40 implantable cardioverter defibrillator implants and a large database of over 500 survivors of myocardial infarction. PROCEDURE: The basic costs of screening tests, stay in hospital, and purchase of implantable cardioverter defibrillators were derived from St George's Hospital during 1991. To assess the cost-efficacy of various strategies for the use of implantable cardioverter defibrillators, survival data taken from published studies or from our own database. Implications of the national cost of the various strategies were calculated by estimating the number of patients a year requiring implantation of a defibrillator if the strategy was adopted. RESULTS: Use of implantable cardioverter defibrillators in survivors of cardiac arrest costs between 22,400 pounds and 57,000 pounds for each year of life saved. Most of the strategies proposed by the current generation of implantable cardioverter defibrillator trials have cost efficacies in the same range, and adoption of any one of these strategies in the United Kingdom could cost between 2 million pounds and 100 million pounds a year. Future technical and medical developments mean that cost-efficacy may be improved by up to 80%. Due to the limitations of screening tests currently available restriction on the use of implantable cardioverter defibrillators to those groups where it seems highly cost-effective will result in a small impact on overall mortality from sudden cardiac death. CONCLUSION: Present and possible future applications of the implantable cardioverter defibrillator seem expensive when compared with currently accepted treatments. Technical and medical developments are, however, likely to result in a dramatic improvement in cost efficacy over the next few years. PMID- 8457403 TI - B-endorphin release in patients after spontaneous and provoked acute myocardial ischemia. PMID- 8457404 TI - B-endorphin release in patients after spontaneous and provoked acute myocardial ischemia. PMID- 8457405 TI - A model to simulate the effects of right heart pulsatile flow after modified Fontain procedure. PMID- 8457406 TI - A posteroseptal accessory pathway located in a coronary sinus aneurysm: diagnosis and radiofrequency catheter ablation. PMID- 8457407 TI - Transepiphysial fixation of anterior cruciate avulsion in a child. Report of a complication and review of the literature. AB - An avulsion of the anterior cruciate of an 11 year old girl was internally fixed with a transepiphysial screw. Two years later, anterior epiphysiodesis was evident, causing hyperextension of the knee. To avoid this complication, we recommend early removal of transepiphysial metalwork in children. Arthroscopical intrafocal fixation is proposed as a safe alternative. PMID- 8457408 TI - Rupture of the pectoralis major muscle in body-builders. AB - Rupture of the pectoralis major muscle is rarely encountered. However, among body builders this lesion, commonly called the "pec-tear", is well known. The bench press exercise is a common cause. In the following report the typical history, symptomatology, and treatment are discussed. PMID- 8457409 TI - Osteochondroma of the femoral neck secondary to a slipped upper femoral epiphysis. AB - Traumatic osteochondromas may develop following damage to the growth plate, but these lesions are rare. Osteochondromas developing secondary to a slipped upper femoral epiphysis (SUFE) have not been previously described. We report such a case and discuss its pathogenesis in relation to the possible aetiologies of primary osteochondromas and SUFE. PMID- 8457410 TI - Cementation in the treatment of giant cell tumor of bone. AB - This study was designed to review the clinical experience of cementation in the treatment of giant cell tumor of bone and to clarify its biologic basis. Eleven patients treated by this technique had results rated excellent. No recurrences of the tumor were found. Serious complications, including infection, late fracture, or secondary osteoarthrosis, did not occur. The possibility of immediate fixation and stabilization of large defects is the most valuable point of this method. Local recurrence seems to be easily detectable by magnetic resonance imaging. A cell line of mononuclear cells from giant cell tumor of bone was examined for its response to hyperthermic exposure. Hyperthermic treatment was carried out at temperature of 60 degrees for 10 min and in other conditions. The numbers of cells surviving after heat treatment were counted, and flow cytometry was used to analyze the positive rate of surface antigens of the cells and the pattern of DNA distribution at the different temperatures. The heat treatment caused a fair number of the cells to fall into S-phase, and the tetraploid value was very low. The higher the temperature and the longer the time, the fewer cells survived and the less the expression of the monocytic phenotype. No cells survived after heating at 60 degrees for 10 min. Cementation seemed to have a hyperthermic effect to the cells of giant cell tumor of bone. PMID- 8457411 TI - Factors influencing survival of the socket after primary low-friction arthroplasty of the hip. AB - Two hundred and sixty-seven consecutive primary low-friction arthroplasties, followed for 5 to 18 years after surgery, were studied to assess the factors influencing survival of the socket, using the Kaplan-Meier method. The end point of survival was defined radiologically in two ways: incipient failure (migration of 3 mm or more or rotation of 4 degrees or more) and definite failure (progressive change of position). Twenty-four sockets (9.0%) developed incipient failure, and 14 of them progressed to definite failure. Preservation of the subchondral bone plate or eburnated bone in the acetabular roof, multiple 6-mm anchor holes, and two steps of evolution in socket design (the advent of a pressure-injection socket and than an ogee-flanged socket) benefited socket survival. Polyethylene wear was considered to be the most important factor limiting longevity of the socket. PMID- 8457412 TI - Degenerative change and rotator cuff tears. An anatomical study in 160 shoulders of 80 cadavers. AB - In order to determine the effects of friction and rubbing in the development of rotator cuff tear, we studied 160 shoulders of 80 cadavers (age at death 43-93 years, mean 69.3 years). Seventy-two cadavers were fixed with formalin and eight were fresh cadavers. The surface of the cuff and the undersurface of the acromion were observed macroscopically. Eight shoulders of fresh cadavers were examined by scanning electron microscopy. Ninety-eight specimens (61%) showed degenerative changes of the supraspinatus tendon. The number of tendons with degeneration and tear increased from the fifth to sixth decade of life, and the size of the tear increased with age. However, there was no sustained increase in the incidence with aging from the age of 60 to 90 years, and the percentage with degenerative changes of the cuff remained at approximately 60% in each decade. Ninety-six specimens (60%) showed degeneration of the subacromial surface. The percentage with degeneration of the undersurface of the acromion remained at approximately 60% from the sixth to ninth decade. There was a significant correlation between the severity of the changes in the rotator cuff and the subacromial surface. Scanning electron microscopy showed changes suggesting effects of friction and rubbing on the rotator cuff, such as regularly arranged wool-like spherical structures on the surface of the tendon and rounded ruptured ends of the tendon fibers. These results indicate that degenerative change of the rotator cuff is aggravated by a friction and rubbing mechanism with the undersurface of the acromion and leads to development of a complete tear. PMID- 8457413 TI - Stress transfer at the femoral bone/bone cement interface as a function of the cement thickness. AB - When a cement canal prosthesis is used as the femoral component in total hip replacement (THR), the penetration depth of the bone cement can be varied according to the cement implantation pressure. Using experimental data which give a relation between the pressure applied to the cement at implantation and the resulting shape of the cement layer, a three-dimensional finite element study was performed to calculate the stress distribution at the bone/bone cement interface. The calculations show that the interface stresses increase with increasing depth of penetration by the cement layer. The explanation of this effect is that as the bone cement penetrates further into the cancellous bone, the cancellous bone is stiffened and can no longer act as a soft interposition between cortical bone and bone cement. From these results and from the clinical requirement that as little bone as possible be destroyed in any kind of allo-arthroplasty, we conclude that the penetration depth of bone cement into cancellous bone in THR should be minimized to the depth necessary in order to achieve sufficient initial stability of the implant. The results show that a cement-canal prosthesis meets these requirements if a cement implantation pressure of 1.0 bar is used. PMID- 8457414 TI - Subcapital fracture of the hip after internal fixation of an intertrochanteric fracture. A case report. AB - We report a case of a subcapital fracture that occurred after reduction and fixation of an intertrochanteric fracture of the hip with a sliding screw. The subcapital fracture occurred 4 months after surgery for the intertrochanteric hip fracture. The subcapital fracture was undisplaced and occurred in an area supported by the screw without damaging the implant. This patient was treated conservatively with bedrest. PMID- 8457415 TI - The quantification of bone tissue regeneration after electromagnetic stimulation. AB - In this study a titanium implant, the bone harvest chamber (BHC), was used to evaluate the effect of electromagnetic stimulation on osteogenesis. The BHC was inserted with a minimum of surgical trauma in the proximal tibial metaphysis in six adult lop-eared rabbits. Bone anchorage occurred after 4 weeks. After implant incorporation bone tissue was harvested at 3-week intervals with the implant in situ without killing the animal. The regenerated bone tissue was analysed by means of microradiography and densitometry. A test group and a control group each comprised six rabbits. The test group was stimulated with a 72-Hz electromagnetic field. Bone tissue was harvested from each tibia six times during the stimulation time and twice after the stimulation had been turned off. The control group had the same harvest procedure performed from one leg. Results showed that electromagnetic stimulation can maintain constant high osteogenetic activity. After the electromagnetic stimulation was turned off the osteogenetic activity diminished rapidly and osteogenesis was significantly lower than during stimulation. PMID- 8457416 TI - Functional or conventional plate prebending in 90 degrees angled blade plate osteosynthesis of intertrochanteric osteotomies. AB - The principle of prebending plates is recommended for intertrochanteric osteotomies to reach satisfactory primary stability. This can be done by conventional or functional prebending. Because of the shape of an overbent plate in conventional prebending, when the tension device is used a sliding of the medial wedge of the proximal fragment medially on the distal osteotomy plane takes place. In functional prebending, the final shape of the plate results in almost no movement of the bone fragments. Therefore the measurable interfragmentary compression of functional prebending is better than in the conventional procedure. The functional prebending also causes no loss of primary installed medialisation and there is no need for an additional procedure for the prebending during the operation. PMID- 8457417 TI - Surgical treatment of Bertolotti's syndrome. Follow-up of 16 patients. AB - We surgically treated 16 patients with Bertolotti's syndrome (chronic, persistent low back pain and radiographically diagnosed transitional lumbar vertebra). Eight had posterolateral fusion and another eight resection of the transitional articulation. Thirteen patients had in addition to the chronic low back pain, suffered from repeated episodes or chronic sciatica. In six cases with resection treatment, local injections were administered at the transitional articulation before deciding for resection of the transitional joint; each patient reported transient relief of pain, while this preoperative test did not correlate with successful outcome of treatment. Six patients had to be treated with second operations. Ten of the 16 operatively treated patients showed improvement of the low back pain, and this result was similar in the group treated with fusion and in that treated with resection. Seven had no low back pain at follow-up, and the improvement according to the Oswestry pain scale was similar in the two groups, and statistically significant. Eleven patients still had persisting episodes of sciatica (versus 13 preoperatively). The average disability according to the Oswestry total disability scale was 30%, corresponding with moderate outcome, and both operatively treated groups did equally well. At follow-up the first disc above the fused segments was found to be degenerated in seven out of eight cases, and in the group treated with resection the first disc above the transitional vertebra was degenerated in five cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457418 TI - Completely remodeled dislocated sternal segment in a child. AB - We report a case of sternal segment dislocation in a child. Although the segment was rotated 90 degrees it was completely remodeled. We now believe that no surgical treatment is necessary for this condition. PMID- 8457419 TI - Charcot's joints: a case report. Osteonecrosis may be a predisposing condition for Charcot's joints. AB - In the case of a patient who had Charcot's joints in her left hip and right shoulders, multiple osteonecrosis in the joints were disclosed by MR imaging. This suggested that osteonecrosis may be a predisposing condition for Charcot's joints. PMID- 8457420 TI - Which investigations are required in stress fracture of the great toe sesamoids? AB - For the athlete a stress fracture of the great toe sesamoid is an injury of fundamental significance. As radiographic findings and bone scintigraphy are not specific, these fractures have the longest delay between first symptoms and definitive diagnosis. Apart from magnetic resonance imaging, the only accurate investigation for early diagnosis is the longitudinal bone scan. PMID- 8457421 TI - An unusual stress fracture of the lateral tibial plateau. AB - Stress fracture of the lateral tibial plateau is a rare occurrence. In this article we report a case of stress fracture of the lateral tibial plateau with a radiolucent fracture line in a 52-year-old man. To our knowledge, such a case has not yet been reported. PMID- 8457422 TI - Popliteal arteriovenous fistula after corrective upper tibial osteotomy. AB - Injuries to the popliteal artery or vein are rare complications of knee arthroscopy or osteosynthesis at the distal femur or the proximal tibia. We report a case of iatrogenic arteriovenous fistula after proximal tibial osteotomy for varus deformity. A 71-year-old woman complained of pain and swelling of the foot 9 weeks after a corrective barrel-vault osteotomy of the left tibia. Angiography demonstrated an arteriovenous fistula between the popliteal vessels due to osteotomy of the tibial head. The fistula was separated and popliteal vessels closed by continuous suture and a small saphenous vein patch. PMID- 8457423 TI - Effect of hypoglycemia on changes of brain lactic acid and intracellular pH produced by ischemia. AB - Previous investigators have attributed the fall of brain intracellular pH (pHi) produced by ischemia to accumulation of lactic acid. The goal of the present experiments was to examine the hypothesis that the acidosis produced by cerebral ischemia is due to accumulation of lactic acid. The present experiments inhibited lactic acid production by lowering glucose availability using insulin-induced hypoglycemia. The adverse effects of hypoglycemia were prevented by the prior elevation of beta-hydroxybutyric acid and acetoacetic acid induced by a high lipid diet. Brain pHi and lactic acid were measured by 31P and 1H NMR. The results showed that insulin-induced hypoglycemia markedly inhibits production of lactic acid, but has no effect on brain pHi during ischemia. These findings suggest that, at least under some conditions, the acidosis produced by cerebral ischemia is not due to accumulation of lactic acid. PMID- 8457424 TI - Energy cost of twitch and tetanic contractions of rat muscle estimated in situ by gated 31P NMR. AB - The phosphagen cost of maximal isometric twitch and tetanic contractions in rat gastrocnemius muscle was measured in situ by 31P NMR with acquisitions gated to precise time points after a brief (< 10 s) burst of contractions. Alteration of twitch stimulation frequency did not affect the energy cost per contraction. Pooled results of four twitch rates from 1 to 8 Hz produced an average cost of 0.257 +/- 0.012 mumol ATP/g/twitch. This value was compared with the initial twitch cost estimated from the time zero derivative of an exponential fit of averaged scan phosphocreatine (PCr) data from a previous study of 8 min of contraction in situ at 0.75 Hz. Agreement of the two estimates validates the use of the fitting/derivative method to assess energy cost and confirms the monoexponential character of the PCr time course. Evaluation of muscle pH changes demonstrated that all ATP use during the brief twitch contraction bouts could be accounted for by PCr hydrolysis. Results also showed a brief delay in onset of PCr recovery, consistent with the response time of oxidative systems. Tetanic contractions of 100 ms duration at 100 Hz required 2.17 +/- 0.07 mumol ATP/g muscle/contraction, in general agreement with estimates reported using a variety of other methods. PMID- 8457425 TI - Relaxation times and concentrations of 7Li in the brain of patients receiving lithium therapy. AB - The present study describes a protocol for the determination of in vivo absolute molar concentrations of Li+ in the human brain using a double tuned 1H/7Li surface coil. The protocol follows the method of Thulborn and Ackerman [J. Mag. Reson. 55, 357-371 (1983)] where the ratio of the signal intensities of 7Li and 1H in the brain is compared to the same ratio in a phantom containing known concentrations of Li+. The 7Li T1 values in the brains of five patients receiving lithium therapy were measured. The average result was T1 = 3.5 +/- 0.25 s. The phantom solution was adjusted to have this T1 value. The protocol was applied for eight bipolar patients receiving lithium therapy. The average ratio of brain to serum lithium molar concentration was found to be 0.59 +/- 0.12. PMID- 8457426 TI - An assessment of artefacts in localized and non-localized 31P MRS studies of phosphate metabolites and pH in rat tumours. AB - UA hepatomas, GH3 prolactinomas and N-methyl-N-nitrosourea-induced mammary tumours, which were subcutaneously grown in rats, have been studied by 31P MRS using non-localized pulse-acquire, image selected in vivo spectroscopy (ISIS) and one-dimensional chemical shift imaging (1-D CSI) techniques. Comparisons have been made with measurements from acid extracts of these tumour types and surrounding tissues (i.e., muscle and skin). Since muscle containing high concentrations of phosphocreatine (PCr) is often found adjacent to the tumour, we have compared the ratio of the PCr to gamma-NTP peaks in the spectra with the same ratio calculated from the acid extract data, and have used deviations between the two sets of data to assess the discrimination of the MRS localization technique to signals from the tissue surrounding the tumour. Extract data showed an average NTP content of 1.25 mumol/g wet wt for all three tumour types. PCr (at 0.42 mumol/g wet wt), was significant only in the GH3 prolactinoma whereas it was negligible in the other tumour types (< 0.1 mumol/g wet wt). There was good agreement between the ISIS PCr/gamma-NTP ratio and the extract data for all tumours. However, the 1-D CSI data showed an unexpectedly large contamination of the tumour spectrum with PCr signals from the skin which was shown by subsequent phantom experiments to be due to the curved geometry of tumour and skin rather than Fourier bleed. In pH measurements by MRS it was found that biological variability was greater than the effects of artefacts (due to either the chemical shift artefact in the ISIS technique or partial volume effects) in the localization technique. An average pH of 7.2 was observed for all tumours. By initially comparing data from different localization schemes with that from chemical extracts potential sources of error have been highlighted and show that phantom studies alone are not sufficient to fully assess the accuracy of localized MRS data. PMID- 8457427 TI - Quantitative 31P MRS of the normal adult human brain. Assessment of interindividual differences and ageing effects. AB - The characteristics of the 31P MR spectra from a large central volume in the brain of 47 healthy adults (aged 25-85 years) were assessed. Spectral parameters were estimated by means of a time-domain fitting technique. Statistical uncertainties of the estimates were determined by means of the Cramer-Rao theory and minimized by introducing a priori knowledge into the fitting procedure. Age dependency of the spectral parameters was assessed by means of linear regression. Significant differences between individuals were established for some parameters. A significant age-dependency (p < or = 0.001) of ca 20% over the age range considered was found for the intensity of the phosphocreatine resonance line. PMID- 8457428 TI - Control of phosphocreatine resynthesis during recovery from exercise in human skeletal muscle. AB - Information about the control of mitochondrial function in skeletal muscle in vivo can be obtained from the relationship between the rate of mitochondrial oxidation and the intracellular concentrations of phosphorus metabolites, although the analysis is complicated by the constraints imposed by the creatine kinase equilibrium. The rate of phosphocreatine (PCr) recovery after exercise measured by 31P MRS is an estimate of net oxidative ATP synthesis. Analysing such data from normal and abnormal human muscle, we show that the approximately exponential recovery kinetics of ADP and PCr imply that the rate of PCr resynthesis has a hyperbolic dependence on [ADP] but remains approximately linear with respect to the concentration of orthophosphate (Pi) and therefore also [PCr] and [creatine]. Both kinds of relationship are consistent with experimental data from exercising animal muscle and also with data from isolated mitochondria which suggest kinetic control of mitochondrial ATP synthesis of [ADP]. These relationships are altered in proven mitochondrial disease. This analysis offers a way to quantify mitochondrial function and its abnormalities in vivo. PMID- 8457429 TI - Aqueous shift reagents for high-resolution cation NMR. VI. Titration curves for in vivo 23Na and 1H2O MRS obtained from rat blood. AB - Frequency shift/concentration calibration curves applicable to the use of shift reagents (SRs) for in vivo 23Na MRS studies can be obtained from experiments with whole blood. Here, they are reported for titrations of rat blood with the SRs DyTTHA3- and TmDOTP5-. There are a number of considerations that must be made in order to derive accurate calibration curves from the experimental data. These include the effects of bulk magnetic susceptibility (BMS, since the SRs are paramagnetic), the effects of water flux (since addition of the SR stock solution to blood renders the plasma hyperosmotic), and the consequences of restricted distribution of the SR anion in the erythrocyte suspension. We give in some detail the BMS shift theory that obtains in this case and show also how it applies to excised perfused organ as well as in vivo studies. Also, we report significant effects of adjuvant Ca2+ additions in the TmDOTP5- titrations. These are very important to the successful use of this SR in vivo. Finally, our considerations of BMS lead naturally to an understanding of its manifestations in the shifts of the 1H2O resonance frequencies of cell suspensions and tissues induced by SRs. Since these are being increasingly reported, and often misinterpreted, we devote an experiment and some discussion to this subject. We show that this phenomenon cannot be used to quantitatively discriminate intra- and extracellular 1H2O signals. PMID- 8457430 TI - The production, buffering and efflux of protons in human skeletal muscle during exercise and recovery. AB - We show how quantitative information about proton handling in human skeletal muscle in exercise and recovery can be obtained by 31P MRS and illustrate this with data from metabolic disorders. Proton production, proton efflux and passive buffering can be distinguished by comparing changes in [phosphocreatine] and pH at the end of exercise and by calculating ATP turnover during ischaemic exercise and in the 'natural experiment' of myophosphorylase deficiency (McArdle's disease). We calculate the effective buffer capacity to be 20-30 mmol/L/pH unit (slykes), somewhat lower than published measurements made in vitro but similar to other values obtained in vivo. This analysis is applied to data from normal muscle and a variety of disease states to estimate proton efflux during recovery and ATP production during exercise: (i) proton efflux during recovery is pH dependent, reaching a 10 mmol/L/min at pH 6.2, and is increased in some cases of mitochondrial myopathy and in hypertension; (ii) glycogenolytic ATP production during exercise can reach 25 mmol/L/min in normal muscle and correlates approximately with [Pi] at the start of aerobic exercise and throughout ischaemic exercise; (iii) oxidative ATP production can reach 20-25 mmol/L/min and (as during recovery) correlates approximately with [Pi]. PMID- 8457431 TI - Absolute quantification and NMR visibility of glycogen in the isolated, perfused rat heart using 13C NMR spectroscopy. AB - NMR spectroscopy, possibly, does not detect 100% of large molecules such as glycogen (mol.wt = 10(7)-10(9)). Using both NMR and chemical quantification methods, we have, therefore, determined the NMR visibility of cardiac glycogen (defined as the ratio of the NMR value to the chemical value, expressed as a percentage) in the isolated, perfused heart. Rats (n = 7) were pretreated for 60 min with 0.2 mg/kg isoproterenol (s.c.) to deplete their endogenous myocardial glycogen stores (mainly 12C). The hearts were then aerobically perfused (65 cm H2O, at 37 degrees C) in a double-walled chamber (the annulus contained a standard), for 70 min with Krebs buffer plus 3.5 mM [13C]1-glucose and 5 mM sodium acetate (natural abundance). From 70 to 175 min the sole substrate was natural abundance acetate (5 mM). 13C NMR spectra for glycogen quantification were acquired in two different ways; by applying 896, 90 degree pulses at 0.33 s intervals with 1H decoupling ('fast', practical spectra) and by applying 896, 90 degree pulses at 5 s intervals ('slow', impractical spectra). Hearts were then removed from the magnet, freeze-clamped (-196 degrees C) and analysed chemically. Cardiac glycogen, quantified from the 'fast' spectra (using conversion factors) and the 'slow' spectra was 16.8 +/- 1.1 and 16.1 +/- 1.8 (mean +/- SEM) mumol glucosyl units/heart, respectively. After correction of the chemical value for the residual [12C]glycogen (determined from 1H NMR spectra of the extracted glycogen after hydrolysis), the NMR-visibilities were calculated to be 101 +/- 6 and 109 +/- 7%, for the 'fast' and 'slow' spectra, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457432 TI - Design and application of NMR-compatible bioreactor circuits for extended perfusion of high-density mammalian cell cultures. AB - MR spectroscopy of cultured cells allows non-invasive analyses of the metabolism of cells with specific phenotypes under defined conditions. This technique can be used to investigate the intracellular metabolism of cells or extended to critically evaluate phenomena observed by in vivo MRS. In this paper, a cell maintenance system is described which allows MR analyses with unparalleled spectral resolution, S/N and stability. This system consists of a 25 mm diameter hollow fiber bioreactor and a supporting circuit. The hollow fiber reactor was chosen because it yields a large filling factor which can be perfused through defined volumes. The fibers were 300 microns diameter microporous (0.2 micron) cellulose acetate/cellulose nitrate membranes with high porosity, which allow bulk convective flow throughout the extracapillary space. This flow (Starling flow) is necessary to disrupt steady-state gradients in substrates and waste products. In many respects, the design of the supporting circuit is more important than the bioreactor itself, since it provides the reactor with the proper chemical and physical environment. Hence, this circuit can be applied to a variety of bioreactor configurations. The circuit consists of a hollow fiber oxygenator and a bleed-and-feed system housed in a temperature-controlled cabinet. Culture of mammalian cells in this reactor yields 31P spectra which have excellent spectral and temporal resolution. At confluence, endogenous 31P line widths were typically < 10 Hz (at 162 MHz) and well resolved spectra were obtained in < 30 s. PMID- 8457433 TI - Outbreak of listeriosis in 1992. PMID- 8457434 TI - British Association for Cancer Research 34th annual meeting jointly with Association of Cancer Physicians 8th annual meeting and British Oncological Association 8th annual meeting. 28-31 March 1993. Abstracts. PMID- 8457435 TI - [Contact poliomyelitis in a patient]. PMID- 8457436 TI - [Nursing of a patient with contact poliomyelitis]. PMID- 8457437 TI - [Physical therapy for a child with poliomyelitis]. PMID- 8457438 TI - [Introduction to the continuing education course--"Home Pediatric Nursing"]. PMID- 8457439 TI - [Continuing education "Home Pediatric Nursing"--report on the new course in Mainz]. PMID- 8457440 TI - [New rules about nursing personnel]. PMID- 8457441 TI - [Position paper of pediatric nursing in general and continuing education]. PMID- 8457442 TI - [Friedrich Ludwig Meissner (1796-1860)]. PMID- 8457443 TI - Plantar malignant melanoma in a white Caucasian population. AB - Fifty-one white Caucasian patients from the west of Scotland, with stage I primary malignant melanoma arising on the plantar surface were studied. Subungual lesions were excluded from the study. Clinical and pathological features were related to survival, and compared with a group of 239 cases of clinical stage 1 melanoma of the lower limb, excluding the foot, collected in the same geographical area over the same period of time (1979-84). The average age of patients with plantar melanoma was 67 years and was significantly older than those with leg melanomas, in whom the mean age was 53 years. Twenty patients with plantar lesions had superficial spreading melanomas, 27 had acral lentiginous melanomas, and four had nodular lesions. The female:male ratio was 3:2 which was significantly different from the 7:1 female:male ratio for leg lesions. Plantar melanomas were more commonly ulcerated (57%) than were melanomas on the leg (29%) [P < 0.001]. There was no significant difference between the mean thickness of melanomas on the plantar surface and those on the leg. Nine (17%) of the patients with plantar melanomas gave a clinical history of pre-existing naevus and in 27% there was pathological evidence of a pre-existing naevus. Disease-free survival at 5 years for the population with plantar melanomas was 82, 51 and 0%, respectively, for melanomas 0-1.49, 1.5-3.49 and over 3.5 mm in thickness. This compares with 95, 71 and 46%, respectively, for leg lesions. In each thickness category patients with leg melanomas have a significantly better survival.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457444 TI - Soluble interleukin-2 receptor in Sezary syndrome: its origin and clinical application. AB - Soluble interleukin-2 receptor (sIL-2R) serum levels were evaluated in Sezary syndrome (SS), mycosis fungoides, non-epidermotropic T-cell lymphomas, inflammatory skin diseases (eczema, psoriasis and lichen planus) and benign erythroderma. All groups displayed mean values significantly higher than controls, and values in SS were also significantly higher than those in the other diseases investigated. Follow-up of 17 SS patients showed that serum sIL-2R correlated with the clinical course of the disease and with other haematological parameters (absolute number of circulating Sezary cells, lactic dehydrogenase). Culture experiments demonstrated that, in contrast with other haematological disorders, highly enriched resting Sezary cells were unable to release sIL-2R, and failed to release normal amounts even after mitogen stimulation. Nevertheless, the leukaemic burden, together with the activation and consequent CD25 expression of leukaemic lymphocytes infiltrating the skin, may justify the hypothesis of a neoplastic sIL-2R source. To further support this hypothesis, the highest sIL-2R values were found in patients with advanced disease, in which normal reactive lymphocytes were dramatically reduced. PMID- 8457445 TI - Skin barrier function in healthy volunteers as assessed by transepidermal water loss and vascular response to hexyl nicotinate: intra- and inter-individual variability. AB - This study assesses the variability of two non-invasive methods of measuring stratum corneum barrier function in vivo. Transepidermal water loss (TEWL), and the vascular response to hexyl nicotinate (HN) penetration as determined by laser Doppler flowmetry, were measured in a group of 21 healthy volunteers. Each time profile of the vascular response to HN penetration was analysed using the following parameters: the baseline cutaneous blood flow, the lag-time between application and initial response (t0), the time between application and maximum response (tmax), the maximum response, and the slope of the curve. TEWL measured on the left volar forearm showed a normal range of 3.9-7.6 g/m2h and a small inter-individual variability [coefficient of variation (CV) 19.4%]. TEWL values at three other forearm sites did not show differences of clinical importance compared with the left volar forearm. The parameters of the vascular response to HN penetration spanned a wider normal range than the TEWL values (CV between 33 and 52%). Repeat measurements after a 1-2 month interval showed highly reproducible individual TEWL values. The mean difference between first and second measurements was only 0.03 g/m2h; the relative difference 0.6%. The intra individual reproducibility of t0 and tmax. for HN penetration was also high (relative differences of 2.8 and 3.1%, respectively). The other vascular response parameters were less reproducible (relative differences of 6.9-18.6%). We conclude that TEWL and selected parameters of HN penetration, as non-invasive tests of the stratum corneum barrier function, yield reproducible results and are hence useful for investigations assessing the skin barrier function in various disorders. PMID- 8457446 TI - A corticosteroid, a non-steroidal anti-inflammatory drug and an antihistamine modulate in vivo vascular reactions before and during post-occlusive hyperaemia. AB - Post-occlusive reactive hyperaemia is the temporary increase of blood flow in a tissue following transient vascular obstruction, and has recently been proposed as an in vivo method for ranking topical corticosteroid potency. We investigated in vivo vascular reactions before and during post-occlusive hyperaemia using laser-Doppler flowmetry and reflectance spectroscopy (RS). RS enables resolution of in vivo erythema into deoxygenated (venous) [DOH] and oxygenated (arterial) haemoglobin (OH) components (expressed in arbitrary units, AU). Using a randomized 24-h occlusive exposure in 10 healthy volunteers the effects of a corticosteroid (betamethasone-17-valerate), a non-steroidal anti-inflammatory drug (NSAID) [indomethacin], an antihistamine (diphenhydramine), or vehicle, were studied before and during post-occlusive hyperaemia. The 24-h vehicle exposure decreased total haemoglobin (composed of a small increase in OH [P < 0.001] and a greater decrease in DOH [P < 0.005], [OH, 0.23 +/- 0.18 AU; DOH, 0.28 +/- 0.12 AU]). The blood flow increased 7.1% to 28 +/- 8 AU (P > 0.05). Betamethasone-17 valerate exposure decreased total haemoglobin further (OH, 0.10 +/- 0.09 AU [P < 0.005]; DOH, 0.18 +/- 0.08 AU [P < 0.05]), which corresponded to a 15% blood flow decrease (P < 0.05). Indomethacin reduced OH to 0.18 +/- 0.12 AU (P < 0.02) and increased DOH slightly, with a trend towards decreased blood flow (P > 0.05). Diphenhydramine caused no significant changes in RS or laser-Doppler flowmetry readings before post-occlusive hyperaemia. Post-occlusive hyperaemia increased total haemoglobin maximally at the first observation time (OH, 0.63 +/- 0.13 AU; DOH, 0.31 +/- 0.11 AU [P < 0.001]).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457447 TI - Antiproliferative effects on keratinocytes of a range of clinically used drugs with calmodulin antagonist activity. AB - Thirty-two drugs, including some in use for a variety of clinical disorders, were examined for their ability to inhibit calmodulin activity in vitro. From these, 10 drugs were selected for their inhibition of calmodulin activity and examined for their ability to inhibit proliferation of rapidly dividing human keratinocytes. A significant correlation between antiproliferative activity and calmodulin antagonist potency was found. Of these drugs there were several, including miconazole, dequalinium chloride, bromocriptine and tamoxifen, whose use is well established and well documented. The potential use of these drugs (and others identified in this way) as antipsoriatic agents is discussed. PMID- 8457448 TI - Immunoblotting of streptococcal antigens in guttate psoriasis. AB - Guttate psoriasis may be precipitated by acute streptococcal infection, usually of the upper respiratory tract. We have studied the immune response to streptococci in 26 patients presenting with a first or recurrent episode of acute guttate psoriasis (AGP), using immunoblotting. Eighteen of 26 patients studied had a demonstrable response to a wide range of streptococcal antigens using this approach, compared with 14 of 26 patients who demonstrated a response using more conventional antistreptococcal antibody tests. Patients with AGP had a significantly higher antibody detection score using immunoblotting than did control subjects (P < 0.005). We conclude that immunoblotting is a useful technique in studying this condition and may be of benefit in exploring the immunopathogenesis of AGP. PMID- 8457449 TI - Renal function and biopsy findings after 5 years' treatment with low-dose cyclosporin for psoriasis. AB - Renal biopsies were performed in eight patients with chronic plaque psoriasis who had been treated with low-dose cyclosporin (CyA) (range 1-6 mg/kg/day; average dose 3.3 mg/kg/day) for an average period of 5 years. In six of the eight patients biopsies showed features consistent with CyA nephrotoxicity. Tubular atrophy and arteriolar hyalinosis were present in all six, four had an increase in interstitium, and two showed an increased incidence of glomerular obsolescence. Two of the patients showed all of these features, two patients had three features, and the remaining patients had two features. Renal function was assessed by glomerular filtration rate (GFR) and serum creatinine. Both a fall in the GFR and a rise in the serum creatinine correlated with the severity of the features of CyA nephrotoxicity seen on biopsy. However, the best predictor of the biopsy findings was a failure of renal function to show significant improvement when CyA was discontinued for a month. CyA has been discontinued in two of the eight patients who had the most severe features of CyA nephrotoxicity on renal biopsy. In both patients there has been improvement of renal function after 1 year of follow-up. PMID- 8457450 TI - Response of psoriasis to twice weekly PUVA. AB - In the U.K., PUVA treatment for psoriasis is usually given three times weekly, with the starting dose of UVA chosen according to the skin type of the patient. Observations on the time-course and dose-response characteristics of PUVA erythema suggest that larger doses of UVA could be used safely, provided that the frequency of PUVA treatment is reduced. We have examined this by treating 100 patients with chronic plaque-type psoriasis with a PUVA protocol in which treatment using oral 8-methoxypsoralen was given twice weekly, with the starting dose of UVA based on each patient's minimal phototoxic dose, and with weekly UVA dose increments calculated as a percentage of the dose used in the previous treatment. Clearance of psoriasis was achieved in 92% of patients. The median number of treatments required for clearance was 12, and the median cumulative UVA dose for clearance was 52J/cm2. Although erythema occurred at some stage during the course of PUVA in 48% of patients, in only 16% of cases was the erythema of sufficient intensity to result in more than one treatment being missed. These results compare favourably with previous studies in which treatment was given three or four times weekly. Thus, twice weekly PUVA treatment for psoriasis is at least as effective as treatment given more frequently, and may be safer, as lower cumulative UVA doses are required for clearance. It also allows for more efficient operation of a PUVA unit and is more convenient for patients. PMID- 8457451 TI - Effect of heliotherapy on skin and joint symptoms in psoriasis: a 6-month follow up study. AB - The effect of heliotherapy on psoriasis skin lesions and arthritis was studied in a trial comprising 4 weeks of therapy in the Canary Islands and a 6-month follow up period. A total of 373 patients participated in the heliotherapy and 361 patients completed the follow-up period. The severity of skin lesions was evaluated using a psoriasis severity index (PSI), and that of the arthropathy by using an arthritis index (AI). During heliotherapy, the PSI decreased significantly from the initial median value of 4.5 to the final value of 0.2. A reduction in the PSI of at least 75% was achieved in 84% of the patients. Guttate psoriasis improved significantly better than plaque-type or erythrodermic psoriasis. There was no correlation between skin type and improvement. Initially, 129 patients had symptoms of arthritis. During heliotherapy, the AI decreased significantly from the initial median value of 6 to the final value of 2. The median time until starting another treatment after heliotherapy was 80 days, and the PSI had returned to its original value in 49% of the patients in 6 months. In patients with joint symptoms the AI returned to the pretreatment level within 6 months. A 4-week heliotherapy period effectively cleared psoriasis, alleviated joint symptoms, and reduced both morbidity and treatment requirement to a considerable extent in the ensuing 6-month period. PMID- 8457452 TI - Urokinase-type plasminogen activator in human eccrine sweat. AB - The presence of urokinase-type plasminogen activator (uPA) in human eccrine sweat has not been reported previously. Clean sweat was obtained from the upper trunk and arms of subjects which had been painted with white petrolatum to minimize epidermal contamination. Sweat was concentrated x 50 by ultrafiltration, and its PA activity determined by the two-step assay method (conversion of plasminogen to plasmin with the subsequent assay of plasmin activity using the substrate S 2251). PA activity was detectable in nine of 17 subjects by this method, which probably represents an underestimate of the true activity because of possible loss of the enzyme during concentration. Scraped (crude) sweat samples contained less PA activity. Sephacryl S-200 gel chromatography of the PA-positive pooled sweat showed a major peak of PA activity at M(r) 55,000. Gelatin-polyacrylamide enzymography revealed a major PA band at M(r) 55,000 and a minor band at 33,000. Sweat PA activity was 94% inhibited by epidermal PA inhibitor and anti-uPA IgG, but not by anti-tPA IgG. We conclude that the PA activity in sweat is derived from the sweat gland and is most likely of the urokinase type. The physiological significance of sweat uPA remains to be determined. PMID- 8457453 TI - Large increase of Langerhans cells in human skin lymph derived from irritant contact dermatitis. AB - In order to monitor the kinetics of Langerhans cells in the afferent lymph during contact dermatitis, a superficial peripheral lymph vessel draining the skin of the upper and medial part of the foot was cannulated by means of microsurgery on the lower leg of four healthy volunteers. After 2 days an irritant contact dermatitis was induced by application of 10% sodium lauryl sulphate to the area of skin drained by the cannulated lymph vessel. Three days later the spontaneously regressing skin reaction was treated with clobetasol propionate in two of the subjects. Lymph was collected twice daily for 8 days. Langerhans cells were identified by immunofluorescence microscopy of cytocentrifuge slide preparations from the lymph, using a monoclonal anti-CD1a antibody. In the late phase of the contact dermatitis the output, i.e. both the absolute number and the percentage of Langerhans cells in the lymph dramatically increased. At the end of the experiment, when there were no remaining clinical signs of contact dermatitis, the Langerhans cell output still markedly exceeded the initial values. These results are the first direct evidence in humans that migration of Langerhans cells from the skin to the regional lymph nodes is a major feature of irritant contact dermatitis. PMID- 8457454 TI - A sclerodermatous syndrome with unusual features following prolonged occupational exposure to organic solvents. AB - We describe a sclerodermatous syndrome in a middle-aged man who had worked with a wide variety of organic solvents over a prolonged period. Associated changes included cold sensitivity, a restrictive lung defect, peripheral neuropathy, oesophageal dysfunction, labile hypertension and a monoclonal paraproteinaemia. This unique syndrome is discussed in relation to other disorders associated with exposure to organic solvents. PMID- 8457455 TI - Mal de Meleda keratoderma with pseudoainhum. AB - Pseudoainhum is an infrequent complication in the autosomal-recessive keratodermas. We describe two related families in which the diagnosis of mal de Meleda keratoderma has been confirmed by mode of inheritance and ultrastructural findings. One family member, a 9-year-old girl, developed pseudoainhum which threatened the viability of her little fingers. This responded to treatment with etretinate. The treatment dilemma posed by keratoderma-induced pseudoainhum in children, i.e. the concern over the possible skeletal toxic effects of long-term etretinate treatment vs. the risks and outcome of surgery, is discussed. PMID- 8457456 TI - Can cyclosporin A induce permanent remission of atopic dermatitis? AB - Three adult patients, who had suffered from severe therapy-resistant atopic dermatitis since childhood, were treated with long-term (29, 44 and 22 months) low-dose (maintenance dose: 0.5-0.7 mg/kg) cyclosporin A (CyA). All responded rapidly within 3-5 weeks and exhibited only minor exacerbations during the first phases of therapy. No relapse occurred in any of the patients after drug withdrawal. All patients remained symptom-free, except for occasional very mild and easily manageable localized lesions, for follow-up periods of 34, 13 and 22 months. Side-effects were minimal or tolerable (mild hypertrichosis in two patients, a slight decrease of creatinine clearance in one). In contrast with the clinical improvement, all atopy-related parameters such as blood eosinophilia, elevated IgE levels and specific IgE (RAST) reactivity remained essentially unchanged, as were skin dryness and stigmata of atopy. It is concluded that long term low-dose CyA treatment may lead to permanent or long-term total or subtotal remission of atopic dermatitis. PMID- 8457457 TI - Scabies associated with a bullous pemphigoid-like eruption. AB - We report a patient who developed a bullous-pemphigoid-like eruption associated with scabies. A subsequent recrudescence of the scabies was associated with recurrence of the bullous eruption. PMID- 8457458 TI - Solitary nodular Langerhans cell histiocytosis. PMID- 8457459 TI - Soft-tissue chondroma as a cause of calcinosis in a patient with CREST syndrome. PMID- 8457460 TI - Direct and objective measurement of the area of leg ulcers. PMID- 8457461 TI - Interferon-gamma and interleukin-2 production by peripheral blood mononuclear cells from a patient with gold contact allergy. PMID- 8457462 TI - Tranexamic acid (Cyklokapron)-induced fixed-drug eruption. PMID- 8457463 TI - Pyoderma gangrenosum treated with low-dose cyclosporin. PMID- 8457464 TI - Reversible adult-onset cyclic haematopoiesis with a cycle length of 100 days. AB - Cyclic neutropenia is the most frequent of the cyclic haematopoietic disorders characterized by its regular 21 d cyclic fluctuations in the number of blood neutrophils, and in many cases simultaneous fluctuations in the other blood cell lines. In this paper we describe a 77-year-old woman with a cyclic pancytopenia including all the myeloid cell lines and to some extent the lymphocytes with a constant and predictable oscillation period of about 100 d. Serial bone marrow biopsies and plasma lactoferrin measurements indicated a similar fluctuating pattern in the bone marrow production of neutrophils. Serial measurements of plasma GM-CSF concentration pointed at a simple feed-back inhibitory system. The condition was present for at least 4 years, after which it gradually improved, although the thrombocyte count still showed a fluctuating tendency after a further 4 years of observation. The clinical consequences were mild symptoms of anaemia and a few episodes of respiratory infections occurring during pancytopenic periods. We think this is the first case described in the literature with this variant of a cyclic haematopoietic disorder. The precise pathophysiological mechanism behind this condition is obscure, but probably it is due to a regulatory disturbance at a very early step in the haematopoietic stem cell hierarchy. PMID- 8457465 TI - Abnormal neutrophil chemotaxis in Gaucher disease. AB - The tendency towards infection described in Gaucher disease patients has been attributed to their post-splenectomy state. We noticed that certain patients with intact spleen have also suffered from recurrent pyogenic infections, thus an attempt to study their neutrophil function has been made. Nine of 29 patients studied expressed significant decrease in neutrophil chemotaxis directed towards zymosan activated serum or N-formyl-methionyl-leucyl-phenylalanine. Random migration was significantly impaired in five of those nine patients. Adherence of neutrophils to nylon fibres and O2- production were intact. The patients with impaired chemotaxis were significantly afflicted by their disease (early onset of symptoms and severity score index > 10) and most of them had genotypes associated with severe disease (1448/1448 and 1226/84GG). No correlation was found with the spleen status. Three of the patients with impaired chemotaxis, and none of the patients with normal neutrophil function, suffered from recurrent pyogenic infections. It is suggested that the described neutrophil migration impairment may contribute to the tendency towards infection in certain patients with advanced Gaucher disease. PMID- 8457466 TI - Megakaryocyte and erythroid colony formation in essential thrombocythaemia and reactive thrombocytosis: diagnostic value and correlation to complications. AB - Megakaryocyte and erythroid colony formation in vitro by progenitors from the bone marrow and/or blood was studied in 61 patients with essential thrombocythaemia (ET) and 22 patients with reactive thrombocytosis (RT) using the methyl cellulose assay. 47 (77%) of the patients with ET showed megakaryocyte and/or erythroid spontaneous colony formation while 14 (23%) patients did not have any kind of spontaneous colonies. Spontaneous megakaryocyte colony formation was seen in 42 (69%) of the patients and 36 (59%) ET patients showed spontaneous erythroid growth. 31 patients had both types of spontaneous colonies. 11 patients showed only spontaneous megakaryocyte colony formation, and five patients only spontaneous erythroid growth. None of the patients with RT or of the normal controls showed either type of spontaneous growth. Neither the presence of spontaneous megakaryocyte colony formation nor the number of spontaneous colonies correlated with the platelet count. Patients with spontaneous megakaryocyte growth had significantly more often thromboembolic or haemorrhagic problems than those without spontaneous colony formation. In conclusion, it was found that a great majority of patients with ET but none of those with RT grow spontaneous megakaryocyte and/or erythroid colonies. Spontaneous colony formation is strong evidence for a myeloproliferative disorder. The presence of spontaneous colony growth is associated with an increased risk of thromboembolic or haemorrhagic complications regardless of the platelet count, particularly among young patients. PMID- 8457467 TI - Vascular complications of essential thrombocythaemia: a link to cardiovascular risk factors. AB - Essential thrombocythaemia (ET) is a myeloproliferative disorder characterized by absolute thrombocytosis and increased incidence of thrombosis and haemorrhage. We report higher morbidity in patients with ET due to arterial ischaemic complications when cardiovascular risk factors are present. In this retrospective analysis of 46 patients, arterial complications occurred in 20/46 patients (43.4%); patients with cardiovascular risk factors, especially cigarette smoking, had more than twice as many arterial complications than patients without risk factors (62.5% v 22.7%, P < 0.05). Neither age, gender nor degree of thrombocytosis were linked to the number of complications. In contrast, we observed no association between cardiovascular risk factors and venous thrombosis or haemorrhagic complications of ET. PMID- 8457468 TI - Transcriptional and post-transcriptional regulation of IL-1 beta, IL-6 and TNF alpha genes in chronic lymphocytic leukaemia. AB - The present study was designed to define the mechanisms of interleukin-1 beta (IL 1 beta), interleukin-6 (IL-6) and tumour necrosis factor (TNF-alpha) gene regulation in chronic lymphocytic leukaemia of B cell origin (B-CLL). By nuclear run-on analysis, all B-CLL cases displayed high levels of nuclear transcription of the IL-6 and TNF-alpha genes, whereas IL-1 beta gene transcription was only barely detectable. Upon in vitro culture for 1 h, B-CLL cells from different patients were substantially heterogeneous in terms of expression of steady state mRNA levels of IL-1 beta, IL-6 and TNF-alpha even though the pattern of nuclear transcription of these cytokines was only marginally affected by in vitro culture. mRNA stability was then examined and cytokine gene transcripts showed a half life of more than 2 h in cultured B-CLL cells and treatment with cycloheximide (CHX) did not affect cytokine transcript levels in B-CLL cells. These results indicate that: steady state levels of each mRNA do not reflect the rate of nuclear transcription of these cytokines in fresh or cultured B-CLL cells, that purification and in vitro culture of leukaemic cells may amplify cytokine gene expression in B-CLL, and that cytokine gene transcripts are relatively stable in B-CLL. PMID- 8457469 TI - CD3 down-regulating factor in sera and culture supernatants of leukaemic cells from patients with adult T cell leukaemia. AB - Immunological abnormality of T lymphocytes in patients with adult T cell leukemia (ATL) is characterized by abnormal expression of the 55 kD chain of the receptor for interleukin 2 (IL-2R/p55) (Tac), and the down-regulation of CD3 expression. Using serum and culture supernatants of leukaemic cells from ATL patients (Group A) whose CD3 expression was down-regulated and those (Group B) whose CD3 was not low, the possible mechanism of CD3 down-regulation on ATL cells was discussed. When PBMC from normal individuals were cultured with sera from ATL patients for 24 h, CD3 expression revealed by mean fluorescent intensity (MFI) was down regulated by sera from ATL patients in Group A (MFI: Pt 1 = 51.6 +/- 4.5, Pt 2 = 48.0 +/- 6.9, control = 96.5 +/- 6.6), not by sera from patients in Group B (MFI: Pt 3 = 105.5 +/- 7.9, Pt 4 = 102.5 +/- 8.3, control = 96.5 +/- 6.6). When normal PBMC were cultured with supernatants of leukaemic cells from ATL patients in Group A, this CD3 down-regulating activity was also detected (MFI: Pt 1 = 78.0 +/ 10.2, Pt 2 = 70.6 +/- 8.7, control = 94.0 +/- 6.6). By using gel-chromatography, the fractionated supernatants from ATL patients in Group A decreased CD3 expression of normal PBMC significantly (MFI: Pt = 22.9 +/- 5.8, Pt 2 = 28.8 +/- 7.4, control = 92.1 +/- 9.6). This CD3 down-regulating activity in fractionated supernatant was not inhibited by any lymphokine antibodies, anti-IL-1 alpha antibody (Ab), anti-IL-1B Ab, anti-IL-2 Ab, anti-IL-3 Ab, anti-IL-4 Ab, anti-IL-6 Ab, anti-TNF-alpha Ab and anti-IFN-gamma Ab. Any known cytokines (IL-1, IL-2, IL 3, IL-4, IL-6, TNF-alpha and IFN-gamma) could not modulate CD3 expression of normal PBMC. These findings suggested that there are novel factor(s) with CD3 down-regulating activity in the serum and culture supernatant of ATL patient and those factor(s) are involved in progression of ATL. PMID- 8457470 TI - Endogenous lymphokine activated killer cell activity and cytogenetic response in chronic myelogenous leukaemia treated with alpha-interferon. AB - The capacity of alpha-interferon (alpha-IFN) to induce lymphokine activated killer (LAK) cytotoxicity in the absence of interleukin-2 (IL2) has prompted us to test whether or not its ability to reduce dramatically the number of Ph1+ clones in chronic myelogenous leukaemia (CML) patients is in part mediated through the generation of natural killer (NK) or LAK activity. The latter were tested using NK-sensitive (K562) and NK-resistant (Raji) cell lines in a target cell colony-growth inhibition assay. Effector cells (E) were patient blood mononuclear cells (MC) without in vitro activation prior to their coculture with targets (T). Out of 16 patients tested so far, three failed to undergo cytogenetic remission under alpha-IFN therapy. No NK nor LAK cells could be detected in the MC from two of them while the other displayed NK activity within upper normal limits. 13 patients underwent complete (eight) or partial (five) cytogenetic remission together with significantly high NK and/or LAK activity as compared to normal controls. These observations could favour the hypothesis of an indirect effect of alpha-IFN on leukaemic cells, mediated by cells involved in immune surveillance. PMID- 8457471 TI - C-fms protein expression by B-cells, with particular reference to the hairy cells of hairy-cell leukaemia. AB - Although the hairy cells (HCs) of hairy cell leukaemia (HCL) are now thought to be a form of activated B cell, they have long been known to possess certain monocytoid characteristics. Since the proto-oncogene c-fms is a feature of cells of the monocyte/macrophage lineage, we examined HCs for c-fms expression. We found that approximately 80% of peripheral blood HCs expressed the c-fms protein (8/8 cases). Expression of the 150 kD protein by HCs was shown using three different techniques, APAAP, immunofluorescence and immunoprecipitation, using two different antibodies. Other mature B cell lymphoproliferative disorders examined (PLL, CLL and multiple myeloma) did not express c-fms. We also examined the c-fms expression of normal B-cells: both the in vivo activated (low density) fraction of tonsil B cells and tonsil B cells activated in vitro with SAC plus IL 2 expressed the c-fms protein. As in the case of monocytes c-fms expression by HCs was shown to be down regulated by its ligand M-CSF, and by TNF alpha, both caused a decrease in the receptor expression from 80% to 30% and in the intensity of staining from 6 to 3 x 10(4) molecules/cell. However, as for monocytes, GM-CSF treatment of HCs had no effect on the expression of c-fms; alpha IFN also had no effect. M-CSF treatment of HCs also induced phosphorylation of c-fms, and a number of other proteins, on tyrosine. However, M-CSF was unable to induce HC proliferation either alone or in combination with IL-2, IL-4 or IL-6; in addition it had no effect on HC proliferation induced by SAC, anti-mu or TNF alpha. In addition, M-CSF either alone, or in combination with the above cytokines, had no effect on the differentiated state of HCs as shown by both immunoglobulin secretion and surface antigen expression. M-CSF also had no effect on the morphology or long-term survival of HCs in culture. This study therefore demonstrates that both HCs and activated B-cells express c-fms, and that M-CSF binds to and activates its receptor on HCs. Although c-fms and several other proteins were shown to be phosphorylated in response to M-CSF, the functional consequences of this phosphorylation remain unclear. PMID- 8457472 TI - Immunophenotyping of low-grade B-cell lymphoma in blood and bone marrow: poor correlation between immunophenotype and cytological/histological classification. AB - Results of immunophenotypic examinations of peripheral blood and/or bone marrow (BM), involved in low-grade B-cell non-Hodgkin's lymphomas, were compared with the results of cytomorphological and histopathological examinations in 133 adult patients. 69 cases of chronic B-lymphocytic leukaemia (B-CLL), 16 centrocytic (CC) lymphomas, 14 centroblastic-centrocytic (CB/CC) lymphomas, 15 immunocytomas (IC), 10 cases of hairy cell leukaemia (HCL), four prolymphocytic leukaemias (PLL), two B-CLL in transformation, one splenic lymphoma with villous lymphocytes (SLVL), one hairy cell leukaemia variant (HCL-V), and one lymphocytic lymphoma (LC) were classified according to the Kiel and/or FAB classification. Leukaemic disease was found in 105 cases. The following markers were used for immunocytology (APAAP technique) of blood and/or BM smears: CD19, CD5, CD10, CD11c, CD14, CD21, CD22, CD23, CD25, CD38 and TdT. All cases tested showed CD19, but no TdT expression. Every case of HCL had a distinct phenotype with expression of CD11c, CD22 and CD25 and the lack of CD5 and CD23 antigens. In all other NHL cases a very heterogenous expression of CD-antigens with no significant correlations to the cytomorphological subtypes was found. The expression of CD5 is a frequent but inconstant finding in lymphoproliferative diseases other than B CLL, so 50% of CB/CC, 75% of CC and 80% of IC were CD5 positive. Our results indicate that, with the exception of HCL, the diagnostic relevance of immunophenotyping for the classification of cytomorphologically and histopathologically defined subtypes in blood and/or BM is of very limited value. PMID- 8457473 TI - Cyclophosphamide and etoposide therapy with GM-CSF for VAD-resistant multiple myeloma. AB - Few effective regimens are available for patients with advanced multiple myeloma resistant to or relapsing after both alkylating agents and VAD. We treated 52 patients with advanced and refractory multiple myeloma with the combination of cyclophosphamide (3.0 g/m2) and etoposide (900 mg/m2) followed by GM-CSF at a daily dose of 0.125 mg/m2 until recovery of granulocytes. 42% of patients responded with a median time of 19 d for recovery of granulocytes to 0.5 x 10(9)/l and a 4% mortality rate. Eight responding patients received a second myeloablative treatment supported by either autologous bone marrow (six patients) or blood stem cells (two patients). The median survival time for all patients was 11 months and the median remission time for responding patients was 8 months. The combination of cyclophosphamide and etoposide provided an effective rescue treatment for many patients with advanced multiple myeloma resistant to conventional therapies. This programme also allowed early marrow or blood stem cell collection in support of subsequent myeloablative therapy for selected patients. PMID- 8457474 TI - UVB radiation exposes fibrinogen binding sites on platelets by activating protein kinase C via reactive oxygen species. AB - Previous studies have shown that ultraviolet B (UVB) radiation causes platelet aggregation by exposing fibrinogen binding sites via activation of an intracellular mechanism. In the present study we have further investigated the routes of platelet activation following UVB exposure. Evidence is provided that UVB radiation does not activate the platelets via the classical Phospholipase A2 and Phospholipase C routes. Despite this observation, UVB-induced fibrinogen binding was found to be correlated with a 40% increase in phosphorylated 47 kD protein. Both findings could be completely inhibited in the presence of staurosporine, a potent inhibitor of protein kinase C (PK-C). In efforts to explain the mechanism of PK-C activation by UV radiation we found that both UV induced PK-C activation and platelet aggregation were significantly reduced in the presence of specific scavengers for reactive oxygen species including superoxide dismutase and catalase. We conclude that exposure of platelets to UVB radiation can activate PK-C via oxygen radicals, resulting in exposure of fibrinogen binding sites and subsequent platelet aggregation. PMID- 8457475 TI - Carrageenan-induced activation of human platelets is dependent on the phospholipase C pathway. AB - Stimulation of washed human platelets by the pro-inflammatory polysaccharide carrageenan is accompanied by shape change, aggregation and release of granule contents and unaccompanied by thromboxane A2 synthesis. Carrageenan triggers platelet activation through a prostaglandin synthetase-independent mechanism. The phospholipase A2 (PLA2) inhibitor, p-bromophenacyl bromide suppresses platelet responses to carrageenan (Vargaftig et al, 1980) probably by mechanism(s) other than those which involve PLA2 activity. Exposure of platelets to carrageenan (2 25 micrograms/ml) induced inositol phosphate formation in a time- and concentration-dependent manner, the level of inositol phosphate formation correlating with the intensity of aggregation. Neomycin, an aminoglycoside antibiotic which inhibits the phospholipase C-mediated phosphatidylinositol 4,5 bisphosphate breakdown, suppressed both platelet activation and inositol phosphate formation. Inhibition was concentration-dependent with an IC50 value of about 180 microM. Platelet-activating factor (PAF) is not responsible for carrageenan-induced platelet activation and inositol phosphate formation, since exposure of platelets to carrageenan (25 micrograms/ml) in the presence of compound WEB 2086 (100 microM), a PAF antagonist, failed to inhibit carrageenan responses. However, compound Ro 19-3704, a structurally related antagonist of PAF reported to be also an inhibitor of phospholipases A2 and C, inhibited concentration-dependently (0.1-10 microM) aggregation and ATP release induced by carrageenan (25 micrograms/ml). These findings indicate that carrageenan activates human platelets through a phospholipase C-dependent mechanism and show that neomycin, at low concentrations, can be a selective inhibitor of phospholipase C-mediated PIP2-breakdown. PMID- 8457476 TI - The fibrinolytic response to ancrod therapy: characterization of fibrinogen and fibrin degradation products. AB - Ancrod is a purified coagulant venom which renders blood incoagulable by cleaving fibrinopeptide A (FPA) from fibrinogen, but the mechanism involved in the clearance of fibrin from the circulation is unknown. To investigate the fibrinolytic response to ancrod, and to increase understanding of clearance mechanisms, six patients with peripheral vascular disease causing claudication were infused with ancrod at 2 u/kg over 6 h followed by 2 u/kg at 12 h intervals for 38 h. Venous blood samples were taken at time 0, 3, 6, 25 and 49 h for assay of fibrinogen (Fbg), fibrinopeptide A (FPA), total fibrin(ogen) degradation products (TDP), fibrin degradation products (FbDP), fibrinogen degradation products (FgDP), cross-linked fibrin degradation products (XL-FDP), tissue plasminogen activator (tPA), urinary type plasminogen activator (u-PA), plasminogen, alpha 2 antiplasmin (alpha 2 AP) and plasminogen activator inhibitor 1 (PAI-1). Fibrinogen (median and range) was 2.3 (1.4-3.90) g/l at time 0 and thereafter was undetectable. FPA rose from 2.5 (1.8-3.6) to 600 and 188 pmol/l at 3 h and 6 h and remained elevated. TDP, FbDP and FgDP increased greatly following ancrod while there was no evidence of XL-FDP. The surprising increase in FgDP during defibrination suggests either that fibrinogen is digested following its incorporation into circulating fibrin protofibrils or that some of the fibrin subunits in the photofibril retain one of the two fibrinopeptide A's. tPA and uPA remained unchanged. Plasminogen fell from 125 (100-155)% to 79 (40-118)% at 49 h and alpha 2 AP fell from 91 (75-107)% to 24 (10-35)% at 49 h. The level of PAI-1 was depressed during defibrination, with the exception of the 6 h data. The results demonstrate that ancrod removes FPA from fibrinogen to produce non-cross linked (soluble) fibrin. This is cleared from the circulation without evidence of an increase in the circulating activities of the plasminogen activators, tPA or UK, but with evidence of plasminogen activation and consumption. PMID- 8457477 TI - Heterogeneous abnormalities of platelet dense granule ultrastructure in 20 patients with congenital storage pool deficiency. AB - Studies on platelet dense granule structure were carried out in 20 patients with various types of congenital storage pool deficiency (SPD), including 15 with specific deficiencies of dense granules and dense granule substances (delta-SPD), and five with combined deficiencies of dense and alpha-granules (alpha delta SPD). Dense granules were identified by their high affinity for uranyl ions (uranaffin reaction), by their ability to accumulate the fluorescent dye mepacrine, and by their inherent electron opacity on unfixed, unstained whole mount preparations. By all these methods, dense granules were markedly decreased in seven albino patients with the Hermansky-Pudlak syndrome (HPS) variant of delta-SPD. These findings suggest that the basic defect in these patients is a specific abnormality in organelle development which prevents the formation of an intact granule structure, a quantitative abnormality which may differ from that in animals with related pigment disorders. In contrast, eight non-albino patients with delta-SPD had, on average, only a slightly reduced number of uranaffin positive and mepacrine-positive granules, but a shift in uranaffin-granule distribution towards those lacking a dense core ('empty granules'), suggesting a more qualitative type of dense granule defect. These results are consistent with previous evidence suggesting a decreased uptake of ATP across the granule membrane in delta-SPD. In addition, on whole mounts, these patients' platelets contained substantial numbers of electron dense chains and clusters which contained P and Ca, but with a P/Ca ratio less than that of typical dense granules, and which were retained, along with a larger amount of ATP, after thrombin treatment of the platelets. The various findings in these patients raise the possibility that these structures may represent microvesicles, derived from the Golgi apparatus, which provide a transport mechanism for concentrating adenine nucleotides and calcium in dense granules and which is impaired in some patients with SPD. Additional defects may account for the more extensive granule abnormalities observed in alpha delta-SPD. PMID- 8457478 TI - Immunological effects of intermediate purity clotting factor concentrates: failure to affect lymphocyte activation in vivo. AB - Concern has been expressed that intermediate purity clotting factor concentrates may cause immunological abnormalities in haemophilic patients, distinct from those related to HIV infection. Early reports of lymphocyte dysfunction in anti HIV seronegative haemophiliacs pointed to activation of their lymphocytes; a potential cause of CD4+ ve lymphocyte decline in anti-HIV seropositive patients. Recent reports have suggested that the use of high purity FVIII concentrates might retard the rate of decline in CD4+ ve lymphocytes in haemophiliacs infected with the HIV virus. Expression of markers of acute and chronic activation of T and B lymphocytes was measured in heavily treated anti-HIV seronegative haemophiliacs using two-colour flow cytometry. No T or B lymphocyte stimulation was observed. Cellular markers of activation were absent and CD4+ ve lymphocyte counts and serum IgG levels were normal. Anti-HIV seropositive haemophiliacs showed T and B cell activation consistent with HIV infection. The extent of lymphocyte activation in individual patients was unrelated to the type, amount or frequency of FVIII received. These findings do not support the hypothesis that lymphocytes of haemophiliacs are affected directly by the regular administration of intermediate purity concentrates so as to accelerate the progression of HIV disease. PMID- 8457479 TI - A new platelet alloantigen, Tua, on glycoprotein IIIa associated with neonatal alloimmune thrombocytopenia in two families. AB - We describe immunization of two mothers against a new platelet alloantigen, designated Tua, in association with thrombocytopenia in their first born children. The platelet-specific antibodies were identified by a glycoprotein specific platelet protein assay with husband's platelets. Monoclonal antibodies against glycoprotein complex IIb/IIIa (AP2) and against glycoprotein IIb (SZ22) could be used to immobilize the antigen bearing protein. When monoclonal antibodies against glycoprotein Ib/IX (FMC25) or Ia/IIa (Gi9) were used, no platelet-specific antibodies were detectable. The previously described alloantigens on the glycoprotein IIb/IIIa complex (HPA 1,3,4, Sra and Vaa) were not responsible for the reaction. Immunochemical analysis by an immunoblot assay showed that the Tua antigen resides on GPIIIa but the antigen was destroyed by reduction of the protein. Altogether 10 individuals belonging to three unrelated families were shown to carry the antigen. The family studies within three generations indicated autosomal codominant inheritance. Thus the Tua antigen is apparently different from all previously published platelet alloantigens. One Tua positive blood donor was identified in a population study of approximately 150 individuals. This indicates a low frequency in the Finnish population. Extended population studies will be required to determine a more exact frequency of Tua antigen. PMID- 8457480 TI - Demonstration of autoreactivity by a human monoclonal IgG anti-Rh D antibody. AB - Human IgG monoclonal antibodies (mabs) against the Rh D antigen have considerable potential for the prophylaxis of haemolytic disease of the newborn. We have carried out in vitro testing for cross-reactions with tissue components by screening two such mabs against animal tissues and a wide panel of human organs from nearly 50 individuals, most of whom were of known Rh D phenotype. Cryostat sections were studied by indirect immunohistochemical techniques. One of the mabs showed non-specific, dose-dependent binding to multiple tissue components whereas the other specifically and consistently reacted strongly with animal smooth muscle and human smooth muscle (vascular, in the walls of hollow viscera, in the respiratory tract) from both Rh D-positive and -negative donors. Immunoprecipitation experiments identified the probable smooth muscle antigen as actin or actin-associated. However, on the basis of inhibition experiments, and by direct estimation of the association constant, the affinity of this mab for smooth muscle was lower than that for Rh D. These results demonstrate autoreactivity by an IgG anti-D mab and show differences in the immunochemical characteristics of human anti-D mabs which may be clinically relevant. PMID- 8457481 TI - The diagnostic significance of serum ferritin indices in patients with malignant and reactive histiocytosis. AB - Iron metabolism was studied in 10 patients with malignant histiocytosis (MH), in 16 patients with histiocytosis-X (Langerhans cell histiocytosis) and in 34 patients with reactive proliferation of the mononuclear phagocytes (MPS). Eight MH patients had a considerably increased level of serum ferritin (SF). The average level of SF was 6070 +/- 957 mg/l for MH patients, which is significantly greater than the SF level for HX and RH patients. The study of the serum ferritin profiles suggests that the main pathogenetic mechanism of hyperferritinaemia in MH is the synthesis and secretion of ferritin by neoplastic mononuclear phagocytes. From this, hyperferritinaemia in MH may be considered as pathognomic of this disease and used as an additional diagnostic criterion. In addition, SF is the most informative parameter for the clinical practice among the indices of the functional state of MPS. PMID- 8457482 TI - Detection of BCR/ABL transcripts in chronic myeloid leukaemia by polymerase chain reaction and DNA enzyme immunoassay: a DNA probe assay without DNA labelling. AB - The detection of the t(9;22) translocation, typical of chronic myeloid leukaemia (CML), can be accomplished by cytogenetical detection of Philadelphia (Ph1) chromosome or by molecular analysis of the bcr/abl fusion gene with nucleic acid probes after amplification by polymerase chain reaction (PCR). PCR-based approaches are now widely used for follow up of CML patients during therapy or after bone marrow transplantation (BMT). We describe here a microtitre, colorimetric assay (DNA Enzyme Immunoassay, DEIA) for analysis of t(9;22) translocation after enzymatical amplification of RNA from CML patients. This assay is based on the use of a monoclonal antibody specifically reacting with double stranded DNA, i.e. with hybridized DNA. The assay represents a nonisotopic alternative to other current hybridization assays and requires no modifications of primers, probe or target DNA. PMID- 8457483 TI - Childhood acute lymphoblastic leukaemia presenting with relapsing hypoplastic anaemia: progression of the same abnormal clone. AB - A 13-year-old girl presented with two spontaneously reversible episodes of marrow hypoplasia. She subsequently developed acute lymphoblastic leukaemia (ALL) 8 months later. Southern analysis showed identical clonal immunoglobulin heavy chain gene rearrangement bands in the leukaemic cells as well as the marrow cells obtained at the two hypoplastic episodes. Hypoxanthine phosphoribosyl transferase polymorphism studies showed that the ALL blast cells, bone marrow and peripheral blood cells during the two hypoplastic episodes all exhibited clonal haematopoiesis with the same X-chromosome inactivated. This case provides strong evidence that aplastic anaemia and ALL may represent evolution of the same abnormal clone. PMID- 8457484 TI - Danazol in autoimmune haemolytic anaemia. AB - Ten adult patients with warm antibody haemolytic anaemia at initial presentation and seven other patients with either refractory AIHA (two patients) or who relapsed after an initial response to prednisone (five patients) were treated with both Danazol and prednisone. 80% of the first group, but also 60% of the second group displayed long-lasting responses (mean follow up 21 months). Minimal side-effects occurred. Finally, addition of Danazol at presentation in warm AIHA may decrease the duration of prednisone therapy and markedly reduce the necessity of second-line splenectomy which is usually required in many patients. PMID- 8457485 TI - Low-grade thrombotic thrombocytopenic purpura associated with HIV-1 infection. PMID- 8457486 TI - Fluconazole chemoprophylaxis in neutropenic patients. PMID- 8457487 TI - The care of the lead worker. 1949. PMID- 8457489 TI - Latency of the Achilles tendon reflex for detection of reduced functions of the peripheral nervous system in workers exposed to lead. AB - The latency of the soleus muscle potential, evoked by a tap of the Achilles tendon, was used in the mass assessment of healthy male workers exposed to lead. Three groups were studied: a control, a low exposure, and a high exposure group. Mean blood lead concentrations were 9.3, 19.2, and 53.1 micrograms/100 ml respectively. Latencies were adjusted for age and height and then compared among the three groups. The mean corrected latency of the high exposure group showed a 4% increase compared with the other two groups (p < 0.01). The latencies of the other two groups showed no between group differences. These results were consistent with previous neurophysiological studies done by many researchers on workers exposed to lead. They suggested that nerve conduction velocities decreased from 3 to 13% among workers whose mean blood lead concentrations were more than 30 micrograms/100 ml. The method was simple, time conserving, non invasive, and non-aversive, and provided a quantitative measure of the nerve conduction velocities of peripheral nerves. Thus it may be useful for early detection of occupationally related impairment of peripheral nerves. PMID- 8457488 TI - Occupational asthma and extrinsic alveolitis due to isocyanates: current status and perspectives. PMID- 8457491 TI - Relation between various chromium compounds and some other elements in fumes from manual metal arc stainless steel welding. AB - For the years 1987-1990 160 individual samples of manual metal arc stainless steel (MMA/SS) welding fumes from the breathing zone of welders in four industrial plants were collected. Concentrations of soluble and insoluble chromium (Cr) III and Cr VI compounds as well as of some other welding fume elements (Fe, Mn, Ni, F) were determined. Concentration of welding fumes in the breathing zone ranged from 0.2 to 23.4 mg/m3. Total Cr amounted to 0.005-0.991 mg/m3 (including 0.005-0.842 mg/m3 Cr VI). Total Cr content of fumes varied from 0.1 to 7.4%. The distribution of particular Cr compounds was: 52.6% soluble Cr (including 50.7% Cr VI), 65.5% total Cr VI, and 11.4% insoluble Cr VI. The results obtained indicate that MMA/SS welding is a process that could be highly hazardous to human health. Evaluation of occupational exposure has shown that MMA/SS welders may exceed the admissible concentrations of soluble and insoluble Cr VI forms as well as of Mn and Ni. In the plants investigated the sum of the ratios of concentrations of particular welding fumes in the breathing zone of welders exceeded corresponding maximum allowable concentration values by 24 times (including 17 times for total Cr VI). Due to the variety and changeability of particular parameters occurring in the working environment, the composition of MMA/SS welding fumes (in the welder's breathing zone) is so variable that it is not possible to assess the exposure by means of one universal exposure indicator (maximum additive hygienic limit value). The evaluation should be based on the results of measurements of concentrations of particular elements in welding fumes. PMID- 8457490 TI - A mortality study among mild steel and stainless steel welders. AB - A mortality study was carried out in conjunction with the European mortality study among welders coordinated by the International Agency for Research on Cancer (IARC). The study was aimed at assessing risks for lung cancer in relation to exposure to asbestos, welding fumes containing chromium and nickel, and tobacco smoke. The study included a cohort of 2721 welders and an internal comparison group of 6683 manual workers employed in 13 factories in France. The mortality of the two cohorts was studied from 1975 to 1988 by the historical prospective method. Job histories of welders were traced including welding processes used, metals welded, and proportion of worktime spent in welding. Data on smoking habits were collected from medical records. The observed number of deaths were compared with those expected (standardised mortality ratio (SMR)) based on national rates with adjustments for age, sex, and calendar time. The smoking habits of 87% of the whole study population were known. The distribution of welders and controls according to smoking was not statistically different. The overall mortality was slightly higher for welders (SMR = 1.02, 95% confidence interval (95% CI) 0.89-1.18) than for controls (SMR = 0.91, 95% CI 0.84-0.99). For lung cancer, the SMR was 1.24 (95% CI 0.75-1.94) for welders, whereas the corresponding value was lower for controls (SMR = 0.94, 95% CI 0.68-1.26). The SMR for lung cancer was 1.59 among non-shipyard mild steel welders (95% CI 0.73 3.02). This contrasted with the results for all stainless steel welders (SMR = 0.92, 95% CI 0.19-2.69), and for stainless steel welders predominantly exposed to chromium VI (SMR = 1.03, 95% CI 0.12-3.71). Moreover, SMRs for lung cancer for mild steel welders tended to increase with duration of exposure and time since first exposure, leading to significant excesses for duration > or = 20 years and latency > or = 20 years. Such a pattern was not found for stainless steel welders. PMID- 8457492 TI - Lung function in insulation workers. AB - To evaluate the effects of working with modern insulation materials (rock and glass wool), the members of the Copenhagen Union of Insulation Workers were invited to participate in a study based on a health examination that included lung function tests. Three hundred and forty men (74%) agreed to participate, and 166 bus drivers served as the control group. Age distribution, height, and smoking habits were similar in the two groups. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were used as tests for lung function. There were no differences in FVC between the study and control groups, but the insulation workers had significantly lower values of FEV1 (mean 2.51) compared with the controls (mean 3.4 1), independent of smoking habits. Six years before the present study, 114 of the insulation workers participated in a similar study, and eight years after the initial study, the lung function of 59 of the bus drivers was tested. The decline in FVC in insulation workers who smoked was significantly higher (7.7 cl/year) than in bus drivers who smoked (3.1 cl/year); the decline in FEV1 was significantly higher in insulation workers independent of smoking habits (17.0 cl/year v 2.9 cl/year). Self assessed former exposure to asbestos was not associated with lung function in insulation workers. The study concludes that working with modern insulation materials is associated with increased risk of developing obstructive lung disease. PMID- 8457493 TI - An epidemiological study of the health of Sri Lankan tea plantation workers associated with long term exposure to paraquat. AB - Pulmonary function tests (FVC, FEV1, FEV1/FVC%, TLCO, single breath CO diffusion), chest x ray film, renal function (serum creatinine and blood urea nitrogen), liver function (serum alanine aminotransferase, aspartate transferase, and alkaline phosphatase, bilirubin, total protein, and albumin), a haematological screen (haemoglobin and packed cell volume), and a general clinical examination were performed on 85 paraquat spraymen (mean spraying time 12 years) and on two control groups (76 factory workers and 79 general workers) frequency matched for age and years of occupational service. All the subjects were men. There were no clinically important differences in any of the measurements made between the study group and the two control groups. In particular the results of the lung function tests, appropriate for paraquat toxicity of the study group, were similar to those of the control groups. The same was true of blood tests for liver and kidney function. The incidence of skin damage, nose bleeds, and nail damage in the study group was slightly higher than in the control groups but lower than the incidence reported for paraquat workers in previous studies. The results of this study confirmed that long term spraying of paraquat, at the concentrations used, produced no adverse health effects, in particular no lung damage, attributable to the occupational use of the herbicide. PMID- 8457494 TI - Mortality and cancer morbidity among cement workers. AB - OBJECTIVE: To explore associations between exposure to cement dust and cause specific mortality and tumour morbidity, especially gastrointestinal tumours. DESIGN: A retrospective cohort study. SUBJECTS AND SETTING: 2400 men, employed for at least 12 months in two Swedish cement factories. MAIN OUTCOME MEASURES: Cause specific morality from death certificates (1952-86). Cancer morbidity from tumour registry information (1958-86). Standardised mortality rates (SMRs; national reference rates) and standardised morbidity incidence rates (SIRs; regional reference rates) were calculated. RESULTS: An increased risk of colorectal cancer was found > or = 15 years since the start of employment (SIR 1.6, 95% confidence interval (95% CI) 1.1-2.3), mainly due to an increased risk for tumours in the right part of the colon (SIR 2.7, 95% CI 1.4-4.8), but not in the left part (SIR 1.0, 95% CI 0.3-2.5). There was a numerical increase of rectal cancer (SIR 1.5, 95% CI 0.8-2.5). Exposure (duration of blue collar employment) response relations were found for right sided colon cancer. After > or = 25 years of cement work, the risk was fourfold (SIR 4.3, 95% CI 1.7-8.9). There was no excess of stomach cancer or respiratory cancer. Neither total mortality nor cause specific mortality were significantly increased. CONCLUSIONS: Diverging risk patterns for tumours with different localisations within the large bowel were found in the morbidity study. Long term exposure to cement dust was a risk factor for right sided colon cancer. The mortality study did not show this risk. PMID- 8457496 TI - Occupational exposure to organic solvents as a cause of sleep apnoea. AB - A high prevalence of sleep apnoea was found in a group of men occupationally exposed to organic solvents. Workers with long term exposure to organic solvents often report symptoms such as fatigue, forgetfulness, and concentration difficulties. These symptoms are strikingly similar to those reported by patients with obstructive sleep apnoea syndrome (OSAS). This is a frequently diagnosed disorder characterised by disturbed sleep causing psychic or somatic complications and daytime sleepiness. A study was undertaken to evaluate whether people with long term occupational exposure to organic solvents have a higher prevalence of sleep apnoea than the general population. Patients exposed to solvents (66 men) were invited to participate in a screening for sleep apnoea. A static charge sensitive bed was used for the monitoring of respiration movements and pulse oximetry during one night. A classical sleep apnoea was diagnosed if periodic respiration movement exceeded 45% of estimated sleep time and the oxygen desaturation index exceeded 6. The prevalence of sleep apnoea among the men exposed to solvents was compared with the prevalence in the general population (1.4%). The prevalence among the participating exposed men was 19.7% which gave a conservative relative risk estimate of 14.1 (95% confidence interval (95% CI) 7.5 24.2). The results indicate that exposure to organic solvents causes sleep apnoea. An alternative possibility is that people with sleep apnoea are misdiagnosed as cases of solvent induced toxic encephalopathy. The interpretation has importance for the caring of the patient. PMID- 8457495 TI - Use of chest radiographs in epidemiological investigations of pneumoconioses. AB - The International Labour Organisation (ILO) classification of radiographs of pneumoconioses was developed to limit variation in classification of parenchymal abnormalities. In this study the manner in which chest radiographs were interpreted in 134 investigations reported in four peer reviewed journals during the five year period 1985-90 was examined. The approach for applying the ILO system was poorly described in most studies. For example, of 86 investigations using more than one reader, 66.3% described the method of reconciliation, but methods were not consistent among investigations. Our results indicate a number of potential problems in application of the ILO system, and gaps in existing recommendations that should be considered. PMID- 8457497 TI - Circadian variations of acute toxicity and blood and brain concentrations of inhaled toluene in rats. AB - To investigate circadian variations in the acute toxicity of toluene, rats were exposed to it (2000 ppm or 4000 ppm) both in the dark (the animals' active phase) and the light (the inactive phase) for 4 hours. The performance decrements of rats were greater in the light phase than in the dark phase in all time zones of exposure to toluene. In the dark phase, the performance recovered almost to that pre-exposure, whereas a significant delay of recovery was noted in the light phase. The differences in the number of lever presses between exposure to 2000 ppm toluene and control (air) exposure were also greater in the light phase than in the dark phase. Significant differences according to the time of exposure were also found in toluene concentrations in blood and the brain. Both blood and brain concentrations in the light phase were higher than those in the dark phase at four hours after exposure to 2000 ppm toluene or at two hours after exposure to 4000 ppm toluene. These results suggest that there was a significant difference in circadian susceptibility after exposure to toluene, which might be caused by circadian differences in the pharmacokinetics of toluene in the light and dark phases. PMID- 8457498 TI - Inhalation fever: a proposed unifying term for febrile reactions to inhalation of noxious substances. PMID- 8457499 TI - A case-control study of malignant and non-malignant disease among employees of a fiberglass manufacturing facility. PMID- 8457500 TI - Intraocular metastasis. PMID- 8457501 TI - Molecular genetics as a 'probe' in ophthalmology. PMID- 8457502 TI - Prophylactic use of acetazolamide to prevent intraocular pressure elevation following Nd-YAG laser posterior capsulotomy. AB - Fifty four eyes of 54 patients undergoing Nd-YAG laser posterior capsulotomy were randomly assigned to pretreatment with either 125 mg of oral acetazolamide (group A) or placebo (group B). During the first 3 hours following capsulotomy, an intraocular pressure (IOP) rise of at least 10 mm Hg was recorded in eight of the 26 eyes of group B (30.8%) and in none of the 28 eyes of group A (p < 0.01). A rise of at least 5 mm Hg was recorded in 16/26 (61.5%) and 4/28 (14.3%) eyes respectively (p < 0.001). Three eyes of group B developed an IOP greater than 35 mm Hg. We found that pretreatment with a low dose of acetazolamide is highly effective in preventing IOP elevation following Nd-YAG laser posterior capsulotomy. PMID- 8457503 TI - Internal sclerostomy using laser ablation of dyed sclera in glaucoma patients: a pilot study. AB - Twelve eyes of 12 patients with refractory glaucoma were treated with internal sclerostomy using laser ablation of dyed sclera. The technique involves iontophoretic impregnation of the sclera at the limbal region with 1% methylene blue and subsequent delivery of a pulsed dye laser beam to the stained area through a goniolens. The red wavelength of 664 nm generated by the laser is maximally absorbed by the stained sclera and creates a through and through sclerostomy. Successful complete sclerostomy was achieved in seven eyes (58.3%) but there was some reduction of intraocular pressure (IOP) in all cases. Mean prelaser IOP (of all 12 eyes) was 36.6 mm Hg and 1 hour after therapy it was reduced to 20.0 mm Hg. At the end of the follow-up period (mean 16 months) the mean IOP was 23.7 mm Hg; five eyes (41%) maintained their IOP below 22 mm Hg, and the average number of medications per eye came down from 3.25 to 2.25 per eye. Transient corneal burns with Descemet's membrane folds adjacent to the laser impact zone were detected in eight eyes (67%). No major complications like IOP spike, hyphaema, iridodialysis, or retinal detachment have been detected. Clear cornea and dark blue scleral staining are essential for the mechanical success of this procedure. Gonioscopic laser internal sclerostomy of methylene blue dyed sclera is technically feasible and the preliminary results of IOP control in refractory glaucoma are promising. Modifications of the iontophoresis process and laser parameters are currently under investigation in order to improve these results. PMID- 8457504 TI - Transient hyperopia with lens swelling at initial therapy in diabetes. AB - The clinical courses of 10 eyes of five diabetic patients who exhibited bilateral transient hyperopia (maximum: 1:1-4.9 dioptres, spherical equivalent) after initiation of strict control of diabetes with or without insulin are reported. The hyperopia occurred within a few days after abrupt decrease in plasma glucose, progressed to maximum at days 7-14, and regressed gradually over 1 month thereafter. Transient cycloplegia had no effect on refractive error. During hyperopia, there were no significant changes in axial length or corneal curvature. However, thickened lens, decreased anterior chamber depth, and transient cataract were observed to significant degrees. It is suggested that the transient hyperopia, with lens swelling and opacity, was caused by decreased lens refractive index following water influx. PMID- 8457505 TI - Analysis of the incidence of intraocular metastasis. AB - The incidence of metastases to the uvea is compared with that in eight other (extraocular) target sites, in patients with metastatic primary carcinomas of the breast, colorectum, and lungs. The incidence of intraocular metastases from breast cancer is lower than in the eight other target organs surveyed; in the other primary cancers, the incidences were midway between those in the other sites, However, when the incidence of intraocular metastases is viewed in relation to the calculated numbers of cancer cells delivered via the arterial route, the uveal tract is the most highly favoured target site for the development of metastases per unit of delivered cancer cells. PMID- 8457506 TI - Continuous curvilinear (circular) capsulorhexis and planned extracapsular cataract extraction--are they compatible? AB - The successful use of continuous curvilinear (circular) capsulorhexis (CCC) in planned extracapsular cataract extraction (ECCE) is dependent on the feasibility of safe nuclear delivery through the smaller anterior capsular opening. Experimental evidence supports the proposition that the anterior capsular rim can stretch without tearing to dimensions which allow for safe nucleus delivery. Clinical reports of accidental intracapsular expression during nucleus delivery in CCC seemingly contradict the experimental evidence. This paper examines this apparent contradiction and presents clinical evidence in the form of a series of 210 cases of planned ECCE with CCC. The technique used and a detailed analysis of the operative complications are presented. The results indicate that using a modified technique for nucleus delivery, CCC and planned ECCE are fully compatible techniques. PMID- 8457507 TI - Permeability of the blood-ocular barrier in adolescent and adult diabetic patients. AB - The permeability of the blood-ocular barrier was examined by fluorophotometry in adolescent and adult diabetic patients before the onset of retinopathy. The adolescent group consisted of 52 eyes of 52 insulin dependent diabetic patients aged 11 to 19 years and a control group of 10 eyes of 10 normal adolescents. The adult group consisted of 74 eyes of 74 non-insulin dependent diabetics and a control group of 30 eyes of 30 normal adults. The increase in lens autofluorescence in the adolescent diabetic patients compared with the controls was striking and showed a significant positive correlation (r = 0.79, p < 0.0001) with the duration of diabetes. Anterior chamber (AQ) values, an index of the permeability of the blood-aqueous barrier (BAB), increased in the adolescent diabetic patients compared with the controls and showed a significant positive correlation with glycosylated haemoglobin levels. No significant differences from the controls were observed regarding the permeability of the blood-retinal barrier (BRB). In the adult group there was no significant difference in either the permeability of the BRB or the AQ values between the diabetic and the control groups. Our results suggest that adolescent diabetic patients differ from adults in that BAB permeability is increased before the onset of retinopathy, suggesting that this is the cause of the striking increase in lens autofluorescence. PMID- 8457508 TI - Ophthalmic findings in classical galactosaemia--prospective study. AB - Thirty three children with classical galactosaemia diagnosed through newborn screening are considered. It is concluded that cataract formation has a direct relationship with poor dietary control. Erythrocyte galactose-1-phosphate (Gal-1 P) levels do not correspond to cataract formation unless many times higher than normal. The value of crystalline lens biomicroscopy is confirmed as a useful method for monitoring the dietary and biochemical control in classical galactosaemia. PMID- 8457509 TI - X linked exudative vitreoretinopathy: clinical features and genetic linkage analysis. AB - A four generation family in which familial exudative vitreoretinopathy is inherited as an X linked condition is described. Essentially the condition is one of abnormal vascularisation and signs at birth are those of a retinopathy superficially resembling retinopathy of prematurity, retinal folds, or, in advanced cases, enophthalmos or even phthisis. Prognosis depends on the progression of the retinal changes. The family members, including seven affected males and five obligate carrier females, have been types for 20 DNA markers, and linkage analysis suggests a gene locus either at Xq21.3 or at Xp11. As the latter region includes the locus for the gene for Norrie disease, it is possible that this and X linked vitreoretinopathy are allelic. We can further speculate that the differences in severity of the clinical manifestations are dependent only upon the timing of the insult. PMID- 8457510 TI - Nasal administration of retinal antigens suppresses the inflammatory response in experimental allergic uveoretinitis. A preliminary report of intranasal induction of tolerance with retinal antigens. AB - Current immunotherapy of posterior uveitis is non-specific and limited by drug toxicity and unpredictable relapses on therapy. Alternative modes of therapy being investigated using the rat model of experimental autoimmune uveoretinitis (EAU) have included the induction of tolerance with oral administration of milligram quantities of retinal antigens. In this preliminary report we demonstrate that tolerance to retinal antigens can be induced via the upper respiratory tract with microgram doses of antigen, preventing subsequent induction of EAU. PMID- 8457511 TI - The rate of visual field loss in untreated primary open angle glaucoma. AB - The mean rate of visual field loss in untreated primary open angle glaucoma was estimated by comparing the mean age at presentation of patients with early relative visual field loss with the mean age of those who presented with absolute field loss within five degrees of fixation. Analysis of the records of 177 patients indicated that the rate of field loss was related to the level of untreated intraocular pressure. For pressures of 21 to 25 mm Hg, untreated disease is likely to progress from early field changes to end stage in an average of 14.4 years. The same interval for pressures of 25 to 30 mm Hg was 6.5 years and for pressures over 30 mm Hg, 2.9 years. For untreated disease at pressures over 25 mm Hg the interval is estimated at 3.6 years and this is much shorter than the estimated period of 10 years under imperfect treatment and 38 years under optimum treatment identified in a prospective clinical trial of early trabeculectomy in patients with similar intraocular pressures at diagnosis. PMID- 8457512 TI - Proptosis as a presenting sign of extradural haematoma. AB - A conscious 15-year-old boy presented with progressive proptosis and a severe headache 2 weeks after minor blunt trauma to the head. No neurological deficit was present. Computed tomography demonstrated intracranial and intraorbital cyst like masses. At craniotomy a subacute extradural haematoma was found which communicated with an orbital subperiosteal haematoma through a shelved orbital roof fracture. The haematomas were drained and the patient made an uneventful postoperative recovery. Although rare, an extradural haemorrhage should be considered in any patient presenting to an ophthalmologist with progressive proptosis and headache following a head injury. PMID- 8457513 TI - Iris crystals in chronic iridocyclitis. AB - Iris crystals in three patients with idiopathic iridocyclitis, Fuchs' heterochromic iridocyclitis, and iridocyclitis associated with systemic pseudolymphoma are described. Two patients had iris crystals in one eye, and the other patient had bilateral involvement. The number of iris crystals in each eye ranged from one to multiple crystals. Iris crystals were minute and refractile and glistened with light; they have previously been reported to be Russell bodies and to be associated with hypergammaglobulinaemia. However, two of the patients, who underwent serum protein electrophoresis, did not demonstrate hypergammaglobulinaemia. PMID- 8457514 TI - Anterior visual system involvement in non-Hodgkin's lymphoma. AB - Non-Hodgkin's lymphoma may have ocular involvement but optic nerve and chiasmal disease is unusual. Determining the cause of the neuropathy in this group of patients presents major difficulties despite modern neuroimaging and immunocytochemistry. Two patients with NHL are presented; one had an anterior chiasmal syndrome and the other bilateral optic nerve involvement. The first patient was thought to have lymphomatous infiltration and the second a concomitant infection (progressive multifocal leucoencephalopathy). Toxic effects of therapy were considered but finally rejected. The importance of modern neuroimaging and the role of optic nerve biopsy are discussed. PMID- 8457515 TI - Necrotic orbital melanoma arising de novo. AB - A 76-year-old man with compressive optic neuropathy secondary to a retrobulbar mass was managed by orbitotomy and removal of the mass. The lesion proved histopathologically to be an unusual orbital melanoma with massive central necrosis. There was no histopathological evidence of congenital melanocytosis. Dermatological and systemic evaluation before and after orbital surgery revealed no evidence of primary melanoma elsewhere. The patient developed hepatic metastasis 2 years after excision of the orbital tumour. It appears that the melanoma was a primary orbital tumour and not a metastatic melanoma from an occult primary lesion. PMID- 8457517 TI - Presumed corneal intraepithelial neoplasia associated with contact lens wear and intense ultraviolet light exposure. AB - Corneal intraepithelial neoplasia (CIN) is a rare dysplastic process affecting mostly elderly fair-skinned people. A variant of the disease associated with contact lens wear was recently described. The three cases reported here had a history of contact lens wear together with strong ultraviolet light exposure. These two conditions may represent a serious risk factor for the development of CIN. PMID- 8457516 TI - Late onset esotropia in monozygous twins. AB - Monozygous twins who developed typical acute late onset esotropia are described. Neither had evidence of other neurological disease and both responded well to bimedial rectus muscle recessions. This twin presentation suggests a hereditary basis for the development of late onset esotropia in at least some cases. It provides further support for a policy of avoiding invasive CNS investigations in those patients who have binocular potential and are otherwise normal. PMID- 8457518 TI - Intracranial hypertension and papilloedema in chronic inflammatory demyelinating polyneuropathy. PMID- 8457519 TI - Regression analysis of visual field progression in low tension glaucoma. PMID- 8457520 TI - The effects of abomasal infusions of casein or soya-bean-protein isolate on the milk production of dairy cows in mid-lactation. AB - The effects of abomasal infusion of casein or soya-bean-protein isolate (SPI) on milk production were investigated in four Friesian cows in mid-lactation receiving a basal diet of grass silage and barley which supplied energy and protein considerably in excess of requirements for milk production by conventional rationing standards. Three levels of infusion were used for each protein source, the corresponding doses being isonitrogenous for each of the proteins: 100, 220 and 330 g/d for casein and 115, 230 and 345 g/d for SPI. Casein produced much greater effects on the yield of milk and milk constituents than did SPI. On the highest dose of casein, milk yield was increased by 3.5 kg/d, fat output by 15% and protein output by 36%; corresponding values for the highest dose of SPI were 1.6 kg/d, 12% and 13% respectively. Increases in the yield of milk-protein were linear for casein but for SPI there was no increase beyond the first level of infusion. It was calculated that casein infusion had a marked effect on the utilization of energy: the increases in milk production could be explained either by a channelling of an extra 12 MJ metabolizable energy (ME)/d away from body tissue synthesis and into milk synthesis or by an increase in the efficiency of utilization of ME for lactation from 0.50 on the basal diet to 0.58; the measurements made did not allow the two mechanisms to be clearly differentiated. PMID- 8457521 TI - Temporal responses of protein synthesis in human skeletal muscle to feeding. AB - In attempting to evaluate alterations in metabolic responses to dietary nutrients that occur in pathological conditions in man, it is first necessary to understand normal metabolic responses. The present study set out to determine the temporal responses of protein synthesis in the skeletal muscle of healthy subjects to the consumption of food. Sequential measurements of protein synthesis in quadriceps muscle were made in eight subjects by injection of 0.05 g L-[1-13C]leucine/kg body-weight. The rate of protein synthesis after an overnight fast (i.e. in the post-absorptive state) was 2.2% muscle protein. After 1 h of eating, protein synthesis was unaltered (2.2%/d), but after 10 h of consuming small hourly meals the rate had risen to 2.9%/d, with a variation in response among individuals. The response of muscle to 10 h of feeding was also investigated in subjects who underwent only one measurement each, either after 10 h of eating small meals or after the same time-period when no food was given. Protein synthesis rates were only slightly elevated in the group of fed individuals (2.3%/d, n 6) compared with the fasted group (2.1%/d, n 6). Taken together the two studies suggest that in healthy adults muscle protein synthesis does not respond quickly to the influx of dietary nutrients and that even after 10 h of feeding any stimulation of protein synthesis is small. PMID- 8457522 TI - The effect of a cold environment on protein and energy metabolism in calves. AB - Eleven Holstein bull calves 35 d of age were assigned to one of three treatment groups: (1) W72, warm environment (20 degrees), 72 g feed/kg body weight (BW)0.75 per d, (2) C72, cold environment (-5 degrees), 72 g feed/kg BW0.75 per d, or (3) C90, cold environment (-5 degrees), 90 g feed/kg BW0.75 per d. Fractional synthesis rates (FSR) of protein in the rumen wall, rumen papillae, omasum, duodenum, kidney, liver, heart, longissimus dorsi, biceps femoris and skin were determined following a continuous infusion of [3H]phenylalanine. Phenylalanine flux was elevated in both groups of cold-adapted calves. FSR of protein in the two muscles and skin were reduced along with N retention in the calves in the C72 group compared with the other two groups. Muscle protein degradation, estimated from urinary N tau-methylhistidine excretion, tended to be elevated in both groups of cold-adapted calves. Reduced protein synthesis and increased protein degradation in the C72 group contributed to reduced muscle protein gain. It appears that when feed intake is limited in cold-adapted animals, muscle and skin have a lower priority for nutrients than other organs and tissues, resulting in reduced protein synthesis. It seems unlikely that thermogenesis due to enhanced protein synthesis contributed to the increased heat production in the cold. PMID- 8457523 TI - The effect of different dietary fats on gastrin levels in the pyloric antrum and plasma of weaner and adult Wistar rats. AB - The effect of dietary fats on gastrin in the pyloric antrum and plasma of Wistar rats was examined. Two different age-groups of rats were fed on three different diets in which fat was in the form of menhaden oil (MO), hydrogenated coconut oil (CO) and safflower oil (SO) respectively. Control groups were fed on normal laboratory diet. Each diet was isoenergetic and no group showed significant differences in either food intake or weight gain during the experiment. Weaner rats fed on the MO diet exhibited significant reductions in both antral (P = 0.047) and plasma (P = 0.002) gastrin concentrations when compared with age matched controls. Likewise, adult rats fed on the MO diet exhibited significant reductions in both antral (P = 0.008) and plasma (P = 0.002) gastrin concentrations. In addition, adult rats fed on the CO diet exhibited significant reductions in both antral (P = 0.047) and plasma gastrin (P = 0.002) concentrations. Rats from both age-groups fed on the SO diet exhibited no significant differences in gastrin concentrations when compared with their respective control groups. These findings indicate that the composition of dietary fat can have profound effects on both tissue and plasma concentrations of gastrin in rats. PMID- 8457524 TI - The effect of replacement of dietary fat by palm oil on in vitro cytokine release. AB - In the present study the effect of replacement of dietary fat by palm oil in the normal Western diet on the in vitro release of the inflammatory cytokines tumour necrosis factor (TNF), interleukin (IL)-6 and IL-8 was examined. A maximal replacement of 700 g/kg dietary fat was achieved for thirty-eight male volunteers who consumed either a palm-oil diet or a control diet in a double-blind, cross over study with 6-week experimental periods, and 3-week run-in and wash-out periods. At the end of both experimental periods, whole blood was stimulated in vitro with 0.02 (sub-optimal), or 10 ng lipopolysaccharide (LPS)/ml (maximal), whereafter TNF, IL-6, and IL-8 concentrations in the culture supernatant fraction were measured using specific enzyme-linked immunosorbent assays (ELISA). Mean cytokine production with sub-optimal, or maximal LPS stimulation of peripheral whole blood was similar for both the palm oil, and the control group. The relative TNF response, however, was reduced by replacement of dietary fat with palm oil. Separate analysis of the data from the first and second experimental periods strongly suggested that the residual effect of the palm-oil diet on the relative TNF response was longer than 9 weeks. Cytokine homeostasis determines the course of the inflammatory response and the progression of atherosclerosis. The effect of palm-oil consumption on the proneness of the peripheral blood cells to produce TNF may, therefore, alter the prevalence of these common diseases. PMID- 8457525 TI - Metabolism of erythritol in humans: comparison with glucose and lactitol. AB - The metabolism of erythritol was assessed in six normal volunteers by measuring the amount of 13CO2 excretion and H2 excretion in breath, and erythritol in urine after intake of 25 g 13C-labelled erythritol. The results were compared with the same variables obtained after intake of 25 g 13C-labelled glucose and 13C labelled lactitol. In addition, the H2 production by faecal flora supplemented with small amounts of erythritol, glucose and lactitol was measured in vitro, as an index of bacterial metabolism of non-absorbed substrate. In contrast to the results obtained after intake of glucose and lactitol, no increase in breath 13CO2 and H2 was observed after intake of erythritol, and erythritol was nearly completely recovered in urine. The in vitro experiments showed that no H2 was formed by faecal flora from erythritol as compared with glucose and lactitol. It is concluded that erythritol is a substrate that is readily absorbed, and undergoes no metabolism by the host. If part of it escapes absorption, it is not metabolized by faecal flora. PMID- 8457526 TI - Fermentation and subsequent disposition of 14C-labelled plant cell wall material in the rat. AB - A 14C-labelled plant cell wall preparation (14C-PCW) produced from spinach (Spinacia oleracea L.) cell culture exhibits uniform labelling of the major polysaccharide groups (%): pectins 53, hemicellulose 13, cellulose 21, starch 3. This 14C-PCW preparation has been used in rat studies as a marker for plant cell wall metabolism. Metabolism of the 14C-PCW occurred largely over the first 24 h. This was due to fermentation in the caecum. The pectic fraction of the plant cell walls was degraded completely in the rat gastrointestinal tract, but some [14C]cellulose was still detected after 24 h in the colon. Of the 14C, 22% was recovered in the host liver, adipose tissue and skin, 26% excreted as 14CO2 and up to 18% was excreted in the faeces. There was no urinary excretion of 14C. In vitro fermentation using a caecal inoculum showed reduced 14CO2 production, 12% compared with 26% in the intact rat. 14C-PCW is a useful marker to investigate the fate of plant cell wall materials in the gastrointestinal tract. These studies show both bacterial fermentation of the 14C-PCW and host metabolism of the 14C-labelled fermentation products. PMID- 8457527 TI - The effects of whole wheat, wheat bran and zinc in the diet on the absorption and accumulation of cadmium in rats. AB - The purpose of the present study was to determine if the inclusion of whole-grain wheat or wheat bran in the diet or the addition of Zn to the diet affects the absorption and accumulation of Cd. Five groups of six rats each were fed deionized water and one of five diets composed of one part basic diet and one part wheat crispbread for 6 weeks. The accumulation of Cd in the liver and kidneys was measured using atomic absorption spectrometry and estimated by measuring the absorption and retention of 109Cd from a single meal after 3 weeks on the diets. The fractional accumulation of Cd in the liver and kidneys was lower in rats fed on whole-wheat and bran diets than in those fed on wheat endosperm diets. As adding Zn or Cd to endosperm diets to approximate the bran and whole-wheat diet levels had no effect on the fractional Cd absorption, the reduced absorption from the whole-wheat and bran diets is probably not due to their higher Zn and Cd concentrations but may be due to their higher fibre or phytate concentrations. The amount of Cd accumulated in the liver and kidneys of the rats fed on whole-wheat and bran diets was higher than that in rats fed on the endosperm diet. Thus, the reduction in the fractional Cd accumulation from the whole-wheat and bran diets is not sufficient to compensate for their higher Cd concentrations. PMID- 8457528 TI - Energy balance in healthy elderly women. AB - There is a paucity of data on which to base estimates of the energy requirements of the elderly. In general, ageing appears to be associated with a reduction in energy requirement arising from a reduction in physical activity and loss of fat free mass. The aim of the present study was to measure the total energy expenditure (TEE), basal metabolic rate (BMR), and energy expended on physical activity (calculated as TEE-BMR) in a group of healthy elderly women living in the community in Southampton. Mean rates of TEE (9.21 (SD 1.48) MJ/d) and energy expended on physical activity (4.12 (SD 1.19) MJ/d) were higher than those observed in some studies of younger adults in the UK, and higher than the factors used to estimate the average energy requirement for the elderly. The results suggest that an age-related reduction in energy requirement is not inevitable and support the hypothesis that the effects of ageing on physical activity, body composition, and hence energy requirements, are variable. PMID- 8457529 TI - Effect of dietary calcium level on mineral and trace element utilization from a rapeseed (Brassica napus L.) diet fed to ileum-fistulated pigs. AB - The bioavailability of intrinsic minerals in rapeseed (Brassica napus L.) meal was studied in growing, fistulated pigs. Furthermore, the effect on mineral availability of an extrinsic Ca supply to this diet, high in phytate, was observed. Comparisons between small intestinal and total gastrointestinal absorption were accomplished for minerals and other dietary components. N retention increased as the dietary Ca intake increased, but dropped, in general significantly, throughout the experimental period, indicating that factors other than protein were limiting for growth. The highest dietary Ca level increased the absorption and retention of Ca and Mg. In contrast, addition of CaCO3 did not influence the apparent absorption and retention of P, Fe, Zn, Cu and Mn. The majority of observed blood variables was not affected by the Ca content of the diet. Zn status-related variables were, however, thoroughly depressed by duration of the experiment and it seems probable that the amount of absorbed Zn was a factor limiting growth. Total gastrointestinal balances showed a Zn retention of 4.7 mg/d, which accounted for 13.6% of that ingested. This low absorption of Zn may have been due to the high intrinsic content of phytate. Apparent absorption of organic matter, ash, N and S was significantly greater calculated from faecal contents than from ileal contents, indicating a disappearance of material in the caecum-colon section of the gastrointestinal tract. The minerals which were studied showed the opposite pattern:apparent small intestinal absorption was larger than total intestinal absorption, suggesting that the caecal-colon region takes part in mineral turnover. PMID- 8457530 TI - Plasma and tissue concentrations of alpha-tocopherol during vitamin E depletion in sheep. AB - To determine the relationship between plasma and tissue alpha-tocopherol concentrations during vitamin E depletion, weaned lambs were placed on a vitamin E-deficient diet for 0, 1, 2, 4, 8 and 12 weeks. alpha-Tocopherol was measured in plasma, erythrocytes, liver, adrenal, adipose tissue, three different skeletal muscles and heart muscle. The alpha-tocopherol concentration in plasma fell at the same rate as the alpha-tocopherol concentration in skeletal muscles, heart muscle, adrenal and adipose tissue. The alpha-tocopherol concentration in liver and erythrocytes fell at a faster rate than that of plasma and all muscle tissues. There were significant correlations between alpha-tocopherol concentration in plasma and alpha-tocopherol concentrations in all the tissues measured. Different skeletal muscles had significantly different concentrations of alpha-tocopherol which may relate to their differing susceptibility to nutritional myopathy. The increase in malondialdehyde in oxidatively-stressed muscle tissue and the correlation with alpha-tocopherol concentration in most muscle tissues indicated that the muscles had reduced antioxidant capacity in vitro as a result of vitamin E depletion. It was concluded that during vitamin E depletion in sheep alpha-tocopherol concentration in plasma was a good index of vitamin E status under the experimental conditions employed. PMID- 8457531 TI - A trial of zinc supplementation in young rural Gambian children. AB - The present study tested the hypothesis that inadequate Zn intake might be responsible for failure to thrive and impaired catch-up growth in young rural Gambian children, and that Zn supplements might be beneficial. Gambian children might be deprived of Zn because of its poor availability from their predominantly plant-based diet. Rural Gambian children (110; fifty boys, sixty girls) aged between 0.57 and 2.30 years were divided into two matched groups, one to receive 70 mg Zn twice weekly for 1.25 years, and the other a placebo. Growth and mid upper-arm circumference were measured at weekly intervals throughout the study and illnesses were monitored. Capillary blood and urine samples were collected at 0, 2 and 8 weeks. Body weights and arm circumferences showed a linear increase, plus a seasonal effect (rainy season faltering). For body weight there was no significant overall effect of the supplement. For arm circumference, a very small (2%) but significant (P < 0.01) difference favoured the supplemented group. Plasma thymulin was much lower at the first clinic than at the second and third clinics, and in vitro Zn stimulation was greater at the first clinic. There was, however, no effect of Zn in vivo. Likewise, Zn did not significantly benefit T cell numbers or ratios, secretory IgA in urine, circulating hormone levels or biochemical indices of Zn status. One index of intestinal permeability, i.e. lactulose: creatinine, was improved (P < 0.02) by the supplement, but the lactulose: mannitol value was not; this requires further investigation. Dietary Zn deficiency is, thus, unlikely to be of major overall importance for rural Gambian children's ability to thrive, and blanket Zn supplementation is not justified. There may, however, be vulnerable sub-groups who would benefit from Zn supplements. PMID- 8457532 TI - Goitre in Ethiopia. AB - A stratified goitre survey was conducted on 35,635 schoolchildren and 19,158 household members in all Regions of Ethiopia except Eritrea and Tigrai. The gross goitre prevalence (mean of male and female values) among schoolchildren and household members was 30.6 and 18.7% respectively, while that of visible goitre was 1.6 and 3.2% respectively. Prevalence was higher in females (27.3% in household members and 36.1% in schoolchildren) than in males (10.1% in household members and 25.1% in schoolchildren) and increased with age more in females than in males. The prevalence rates at higher altitudes were higher than those at lower altitudes in both schoolchildren and household members. Using an epidemiological model the consequences of iodine deficiency, including cretinism and maternal wastage, have been estimated. PMID- 8457533 TI - The effects of chronic cassava consumption, cyanide intoxication and protein malnutrition on glucose tolerance in growing rats. AB - Intraperitoneal glucose tolerance tests were performed at 4-week intervals in groups of weanling rats before and after feeding with maize- or cassava-based diets with and without adequate protein and sublethal cyanide supplementation. Weaning weights were doubled (increase of about 50 g) after 4 weeks on control (maize-based with adequate protein) and protein-replete diets. Weight gain on the protein-deficient diets was much less (22 g or 50%), a pattern maintained by the rats on these diets until the age of 12 weeks. Plasma thiocyanate levels were identical at weaning and after 8 weeks of the control diet but increased by 200 300% after 4 weeks intake of the cassava or cyanide-supplemented feeds. Levels returned to normal in all groups after a further 4 weeks feeding with the control diet. Glucose tolerance (as assessed by the area under the 2 h glucose v. time curve) was impaired to a varying extent in the rats after 4 weeks on the various diets: protein-replete cassava and protein-deficient maize diets by 50% protein deficient cassava diet by 300%, and cyanide-supplemented protein-deficient maize diet by 150%. The derangement in the rats on the protein-replete cassava diet was unaffected by a further 4 weeks intake of the control diet, unlike in the other groups where there was significant improvement in the glucose tolerance indices at the same time. It is concluded that in growing rats: (1) cassava intake and protein malnutrition may have independent and additive effects on the genesis of glucose intolerance, (2) cyanide supplementation of a cassava-free protein replete diet has no effect on glucose tolerance. PMID- 8457534 TI - The effect of an ethanol extract derived from fenugreek (Trigonella foenum graecum) on bile acid absorption and cholesterol levels in rats. AB - The hypocholesterolaemic properties of an ethanol extract from defatted fenugreek (Trigonella foenum-graecum) seeds were investigated. Purification of the crude extract by dialysis produced an isolated component with haemolytic properties. The dialysate was also found to contain saponins demonstrated by thin-layer chromatography. Experiments in vitro employing the everted-sac technique showed that the ethanol extract had the ability to inhibit taurocholate and deoxycholate absorption in a dose-dependent manner. In two separate feeding experiments, hypercholesterolaemic rats were fed on 30 or 50 g ethanol extract/kg for a 4-week period. Reductions in plasma cholesterol levels ranged from 18 to 26% and a tendency for lower concentrations of liver cholesterol was observed. These results indicate that the ethanol extract from fenugreek seeds contained hypocholesterolaemic components which appear to be saponins that interact with bile salts in the digestive tract. PMID- 8457535 TI - The effect of dietary L-carnitine on the growth performance in fingerlings of the African catfish (Clarias gariepinus) in relation to dietary lipid. AB - The effect of dietary L-carnitine on the growth and growth efficiency of African catfish (Clarias gariepinus, Burchell 1822) fingerlings was investigated. Six dietary levels of L-carnitine, varying from the control level (about 125 mg/kg) to 3920 mg/kg, were each tested at two dietary lipid levels (96 and 155 g/kg). The diets were isonitrogenous and were fed to thirty-six experimental groups of 100 fish weighing 5 g at a feeding level of 25.2 g/kg live weight (w)0.8 per d, during 18 d. The average final weight varied from 19.1 to 28.0 g. At a dietary lipid level of 96 g/kg the metabolic growth increased from 30.8 to 36.5 g/kg w0.8 per d. At the higher dietary lipid level the metabolic growth increased from 30.9 to 35.4 g/kg w0.8 per d. To assess the dose-response relationship between dietary L-carnitine and growth performance in the African catfish a linear-plateau model was fitted to the experimental data. According to this model, metabolic growth was at a maximum at L-carnitine levels of 500 mg/kg and above at a lipid level of 96 g/kg and at L-carnitine levels of 684 mg/kg and above at a lipid level of 155 g/kg. The fitted maximum metabolic growth was higher at a dietary lipid level of 96 g/kg (35.9 g/kg w0.8 per d) than at 155 g/kg (34.7 g/kg w0.8 per d). Feed conversion improved significantly with increasing dietary levels of L-carnitine, reaching a fitted plateau at L-carnitine levels of 448.8 and 236.7 mg/kg respectively for the high and low dietary fat levels. Other growth efficiency variables, e.g. protein efficiency ratio, protein retention and energy retention improved accordingly. Taking into consideration that all fish received the same amount of feed, the results of the present study demonstrate that the positive effect of increased levels of dietary L-carnitine is the result of an improved feed utilization, probably because of a stimulated protein-sparing action. PMID- 8457536 TI - Intra- and inter-individual variations in energy expenditure of 14-15-year-old schoolgirls as determined by indirect calorimetry. AB - Eleven 14-15-year-old schoolgirls were investigated four times within 1 year to determine variations in energy expenditure between individuals (inter-individual variability) and within subjects (intra-individual variability). Indirect calorimetry was used to determine metabolic rates in the fasting and resting state (RMR), and during physical activities which were grouped into standardized and non-standardized activities. Analyses of variance supplied information about intra- and inter-individual variabilities of rates of energy expenditure. The mean resting metabolic rate in adolescent girls was 4.41 (SD 0.40) kJ/min. The overall coefficient of variation (9.1%) was approximately twice as high as the mean coefficient within subjects (4.3%). The reproducibility of the RMR of the girls was high (significant F value of variance analysis), even over a prolonged investigation of 1 year. This seemed to depend primarily on the constant body weight during the period of investigation. A workload of 30 W on a bicycle ergometer and walking at an individually chosen speed did not reveal significant differences between inter- and intra-individual variabilities of energy metabolic rates. However, in most non-standardized activities, e.g. relaxation at home, washing dishes and vacuum cleaning, inter-individual variability was significantly higher than intra-individual variability. There are true differences in energy expenditure rates between subjects which may be demonstrated by duplicated measurements. Conclusions on future experimental design were drawn, where differences between groups rather than between individuals are to be studied. PMID- 8457537 TI - The energy and nutrient intakes of different types of vegetarian: a case for supplements? AB - Vegetarians of three types were studied in Greater London: thirty-four meat avoiders, fifty-two lacto-ovo-vegetarians, and thirty-eight vegans. Weighed dietary intake measures were made over 3 d. Cereals were the mainstay of the diet, supplemented by dairy products (demi-vegetarians and lacto-ovo vegetarians), vegetables and fruit, and soya-bean products (vegans). Many vegans progressed by stages to complete avoidance of animal foods; some had retreated, but most were highly committed. Demi-vegetarians were the least involved in a 'vegetarian lifestyle'. All groups had mean energy intakes close to the current dietary reference values (DRV), with adequate protein intakes. Only vegans had fat intakes close to current recommendations; all groups had high dietary polyunsaturated:saturated fatty acid ratios. Mean intakes of all micronutrients studied for demi- and lacto-ovo-vegetarians met the UK DRV. Intakes of iodine, riboflavin, and vitamin B12 for vegans were below DRV; more than half considered their diets supplied all necessary vitamins. About 25% took some type of dietary supplement during the survey. The impact of low I intakes should be further studied, and it is recommended that 'new' vegetarians and vegans should use appropriate dietary supplements. PMID- 8457538 TI - Effect of somatotropin administration and duodenal infusion of methionine and lysine on lactational performance and nutrient flow to the small intestine. AB - Lack of sufficient methionine and lysine delivered post-ruminally may limit milk production response to bovine somatotropin (bST). To test this hypothesis, four Holstein cows fitted with rumen and duodenal cannulas were used in a 4 x 4 Latin square design with 14 d periods. Treatments were: (1) control, (2) continuous duodenal infusion of 8 g methionine and 24 g lysine/d, (3) injection of 25 mg bST/d and (4) infusion of methionine and lysine plus injection of bST. Infusion of amino acids led to trends for small increases in milk (3%), fat (5.5%), and protein (3.7%) yield. Larger and significant increases (8.7, 14 and 6.9% for milk, fat and protein yield respectively) were achieved with bST administration which also increased milk fat content. Plasma levels of urea-N and essential amino acids were reduced with bST. Duodenal nutrient flow was generally unaffected by treatment. The production response to bST was not enhanced in cows producing an average of 34 kg milk when provided additional methionine and lysine post-ruminally in this short-term study. PMID- 8457539 TI - Interactions between major nutrients in the diet and the lactational performance of rats. AB - The effect on lactational performance of replacing feed carbohydrate with fat at two different protein levels was studied. Lactating Sprague-Dawley rats with a standardized litter size of thirteen pups were allocated one of eight feeds containing either 300 or 150 g protein/kg organic matter (OM) and ranging in fat content from 100 to 550 g/kg OM from day 2 until day 14 of lactation. Daily food intake, live-weight gains, and changes in body composition of both dams and litters were measured. Feeds of low protein content resulted in a significant decline (P < 0.001) in lactational performance despite a significant increase (P < 0.001) in maternal protein mobilization. Maternal lipid mobilization was not significantly affected by feed composition. Litter lipid gain was significantly increased (P < 0.05) as fat replaced carbohydrate in the high-protein feeds, due to an increase in maternal energy intake. In contrast, lactational performance was severely depressed (P < 0.001) as fat replaced carbohydrate in the low protein feeds. This interaction between feed components on lactational performance was in accordance with the hypothesis that the heat production of lactating rats is maximal and, hence, constraining intake. PMID- 8457540 TI - Effects of dietary protein and fat level on oxidative phosphorylation in rat heart mitochondria. AB - The effect of dietary protein and fat levels on cardiac mitochondrial oxidative phosphorylation was assessed polarographically. Weanling rats were fed on semi purified diets containing different protein levels (10, 30, 50 and 70%) on a gross energy basis (PGE) for 9, 23 and 58 d. Cardiac mitochondria isolated from rats fed on a 70% PGE diet for 23 d exhibited significantly reduced ADP:oxygen (ADP:O) values compared with mitochondria from rats fed on a low-protein diet. Feeding low-protein diets for 58 d increased the ADP: O value. When the dietary fat level was altered to provide (% PGE: % fat-energy): 30:14, 30:30, 70:14, 70:30, feeding 70% PGE diets reduced the ADP:O value compared with the 30% PGE level, but no difference was observed between low-fat and high-fat groups. These results indicate that the impaired ADP: O value for rats fed on very-high-protein diets was not due to the dietary fat level but that the level of dietary protein is an important determinant of oxidative phosphorylation in rat heart mitochondria. PMID- 8457541 TI - Creation of an NADP-dependent pyruvate dehydrogenase multienzyme complex by protein engineering. AB - Systematic replacement of a set of amino acids in the beta alpha beta-fold of the NAD-binding domain of Escherichia coli dihydrolipoamide dehydrogenase has been used to convert its coenzyme specificity from NAD to NADP. After comparison with the homologous enzyme glutathione reductase, Glu 203 was replaced with a valine residue, thereby eliminating the potential to form hydrogen bonds with the 2'- and 3'-OH groups of the adenine ribose in NAD. Similarly, Met 204, Pro 210, Phe 205, and Asp 206 were replaced by an arginine, an arginine, a lysine, and a histidine residue, respectively, to provide a nest of positive charge to accommodate the 2'-phosphate group of the incoming NADP. In addition, Gly 185 and Gly 189 in the beta alpha beta motif were replaced with alanine residues to facilitate the positioning of the newly introduced Val 203 by allowing a flip of the peptide bond between residues Gly 180 and Gly 181. Wild-type dihydrolipoamide dehydrogenase is inactive with NADP, but the mutant enzyme displayed high levels of activity with this coenzyme, the values of Km, kcat, and kcat/Km comparing favorably with those found for the wild-type enzyme operating with NAD. The mutant enzyme was also capable of assembly in vitro to form an active pyruvate dehydrogenase multienzyme complex, the coenzyme specificity of which reflected that of its dihydrolipoamide dehydrogenase component. These experiments should make it possible now to study the effects in vivo of requiring a crucial catabolic enzyme to function with the wrong coenzyme, an important extension of protein engineering into the living cell. PMID- 8457542 TI - Photoaffinity labeling of central cholecystokinin receptors with high efficiency. AB - A new photoreactive tritiated cholecystokinin (CCK) analogue was synthesized which contains the p-benzoylbenzoyl moiety linked to an ornithine residue at the N-terminus of the sulfated CCK octapeptide (CCK-8s). p-Benzoylbenzoyl Orn(propionyl)-CCK-8s bound specifically and with high affinity to CCK binding sites in membranes both from pig cerebral cortex and from rat pancreatic membranes. The apparent dissociation constants KD were 1.2 nM and 0.5 nM, respectively. [3H]-p-Benzoylbenzoyl-Orn(propionyl)-CCK-8s was incubated with CCKB receptor preparations enriched by lectin chromatography and subsequently photoactivated. A polypeptide migrating with an apparent molecular weight M(r) of 56,000 in sodium dodecyl sulfate-polyacrylamide gel electrophoresis was specifically labeled. The labeling was suppressed by the CCKB receptor agonist pentagastrin. The efficiency of incorporation of radioactivity was high, reaching up to 70% of specifically bound radioactivity. After treatment with trifluoromethanesulfonic acid, the molecular weight of the labeled protein decreased to 45,000, indicating that the receptor is glycosylated. Photoaffinity labeling of CCKA receptors from rat pancreas resulted in the specific labeling of a protein band with M(r) of 80,000-100,000. Our synthetic approach should be useful for the design of photoreactive analogues of a variety of peptides. The high efficiency photolabeling of the CCKB receptor will be valuable for further characterization and purification of this receptor. PMID- 8457543 TI - P05, a new leiurotoxin I-like scorpion toxin: synthesis and structure-activity relationships of the alpha-amidated analog, a ligand of Ca(2+)-activated K+ channels with increased affinity. AB - The venom of the scorpion Androctonus mauretanicus mauretanicus contains a toxin, P05, which is structurally and functionally similar to scorpion leiurotoxin I (87% sequence identity), a blocker of the apamin-sensitive Ca(2+)-activated K+ channels. It is a 31-residue polypeptide cross-linked by three disulfide bridges. A C-terminal carboxyl-amidated analog of P05 (sP05-NH2) was chemically synthesized by the solid-phase technique and fully characterized. Toxicity assays in vivo established that sP05-NH2, like native P05, is a potent and lethal neurotoxic agent in mice (LD50 of 20 ng per mouse). Pharmacological assays in vitro however showed that, unlike P05 which has a binding affinity of 2 x 10(-11) M, sP05-NH2 apparently binds irreversibly to the apamin receptor. Iodination at the C-terminal His gave diiodo-sP05-NH2, which had a binding affinity similar to that of native P05. The disulfide bridge pairings were chemically determined for sP05-NH2 and thereby deduced for P05 and leiurotoxin I: linkages were between Cys3 and Cys21, Cys8 and Cys26, and Cys12 and Cys28. Molecular dynamics refinement of P05 also using data from leiurotoxin I suggests that P05 is mainly composed of a double-stranded, antiparallel beta-sheet (from Leu18 to Val29) linked to an alpha-helix (from Arg6 to Gly16) by two disulfides (Cys8-Cys26 and Cys12-Cys28) and to an extended fragment (from Thr1 to Leu5) by the third disulfide (Cys3-Cys21). In agreement with the model, circular dichroism analysis of sP05-NH2 showed that the toxin structure is highly rigid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457544 TI - A common mechanism for influenza virus fusion activity and inactivation. AB - The fusion of influenza virus (A/PR/8/34 strain) with PC-12 cells was monitored by a fluorescence assay, and the results were analyzed with a mass-action model which could explain and predict the kinetics of fusion. The model accounted explicitly for the reduction in the fusion rate constant upon exposure of the virus to low pH, either for the virus alone in suspension or for the virus bound to the cells. When the pH was lowered without previous viral attachment to cells, an optimal fusion activity was detected at pH 5.2. When the virus was prebound to the cells, however, reduction of pH below 5.2 resulted in enhanced fusion activity at the initial stages. These results were explained by the fact that the rate constants of both fusion and inactivation increased severalfold at pH 4.5 or 4, compared to those at pH 5.2. At pH 5.2, lowering the temperature from 37 to 20 or 4 degrees C resulted in a decrease in the fusion rate constant by more than 30 or 1000-fold, respectively. Inactivation of the virus when preincubated in the absence of target membranes at pH 5 was found to be rapid and extensive at 37 degrees C, but was also detected at 0 degrees C. Our results indicate a strong correlation between fusion and inactivation rate constants, suggesting that the rate-limiting step in viral hemagglutinin (HA)-mediated fusion, that is, rearrangement of viral glycoproteins at the contact points with the target membrane, is similar to that involved in fusion inactivation. PMID- 8457545 TI - An extended X-ray absorption fine structure investigation of the structure of the active site of lactoperoxidase. AB - Native lactoperoxidase, compound III, and the reduced forms (at pH 6 and 9) were studied using X-ray absorption spectroscopy (XAS). Native lactoperoxidase has four pyrrole nitrogen ligands at an average distance of 2.04 +/- 0.01 A, a proximal ligand at 1.91 +/- 0.02 A, and a sixth (distal) ligand at 2.16 +/- 0.03 A. Lactoperoxidase native enzyme has a first coordination shell structure that is similar to that of native lignin peroxidase [Sinclair, R., Yamazaki, I., Bumpus, J., Brock, B., Chang, C.-S., Albo, A., & Powers, L. (1992) Biochemistry 31, 4892 4900] and different from that of horseradish peroxidase [Chance, B., Powers, L., Ching, Y., Poulos, T., Schonbaum, G., Yamazaki, I., & Paul, K. (1984) Arch. Biochem. Biophys. 235, 596-611]. Similarly, lactoperoxidase compound III resembles lignin peroxidase compound III. The five-coordinated ferrous form was stable at pH 9, but at pH 6 it was rapidly converted to the six-coordinated form with a distal ligand at 2.18 +/- 0.03 A. No evidence typical of changes in spin state was obtained at the different pH values. PMID- 8457546 TI - Structural changes in the protease domain of prothrombin upon activation as assessed by N-bromosuccinimide modification of tryptophan residues in prethrombin 2 and thrombin. AB - Increases in intrinsic fluorescence (delta I), reflecting changes in tryptophan environments, occur upon bond cleavages necessary for prothrombin (II) activation to thrombin (IIa) by prothrombinase. Cleavage at Arg274-Thr275 (numbering based on bovine prothrombin sequence, with chymotrypsinogen numbering in braces) between the amino-terminal fragment 1.2 and protease (Pre2) domains of prothrombin yields delta I = 5%, and cleavage within the Pre2 domain at Arg323 Ile324 to form IIa yields delta I = 35%, while cleavage at both yields delta I = 25%. Since the change in fluorescence upon activation of prothrombin can be largely attributed to a change within the Pre2 domain, the susceptibilities of each of the 9 Trp residues of IIa and its immediate precursor Pre2 to oxidation by N-bromosuccinimide (NBS) were compared. Pre2 and IIa were titrated with increasing amounts of NBS (0.5-5 equiv of NBS/TRP), aliquots were removed and fully digested with trypsin, and tryptophan-containing peptides were separated and quantitated by RP-HPLC with fluorescence detection. Tryptic digests yielded 9 tryptophan-containing peptides, which were identified by amino acid composition. Tryptophan residues in IIa and Pre2 displayed a 10-fold range of sensitivity to modification. Tryptophans 337 and 360 (W29, W51) were modified less readily in IIa than in Pre2, while residues 373, 542, and 550 (W60D, W207, W215) were modified more readily, and other residues were equally susceptible. Residues 360 and 373 (W29, W60D) flank the active site histidine. From the crystal structure, residues 373 and 550 (W60D, W215) are implicated in substrate binding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457547 TI - Sensitivity to nitrate and other oxyanions further distinguishes the vanadate sensitive osteoclast proton pump from other vacuolar H(+)-ATPases. AB - The osteoclast proton pump (OC H(+)-ATPase) differs from other vacuolar H(+) ATPases (V-ATPases) in its sensitivity to vanadate and in the subunit composition of its catalytic domain, where isoforms of subunits A and B are expressed [Chatterjee et al. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 6257-6261]. In the present study, the sensitivity of the osteoclast H(+)-ATPase to various oxyanions was tested. The results indicate that H+ transport by microsomal preparations isolated from chicken osteoclasts is 20-100-fold more sensitive to nitrate that any other animal and fungal V-ATPases and 10-20-fold more sensitive than plant V ATPases, as is the ATPase activity of the affinity-purified enzyme. This inhibition by nitrate is not due to a chaotropic effect of the oxyanion and is complete at 1 mM concentrations with an IC50 of 100 microM. In contrast, proton transport by the OC H(+)-ATPase was insensitive to other oxyanions (phosphate, sulfate, and acetate) which inhibit other V-ATPases. These results further demonstrate that the proton pump present in osteoclast membranes differs from other vacuolar ATPases. It is speculated that, since cells of the macrophage lineage can generate high intracellular concentrations of nitrate, it may be possible to physiologically or therapeutically regulate the activity of the OC H(+)-ATPase in the osteoclast without affecting the other V-ATPases in the same or in other cells. PMID- 8457548 TI - Intermediate partitioning in the tartrate dehydrogenase-catalyzed oxidative decarboxylation of D-malate. AB - The oxidative decarboxylation of D-malate catalyzed by tartrate dehydrogenase has been examined in detail. Enzyme-catalyzed partitioning of oxalacetate has been determined to proceed with formation of pyruvate and D-malate in a ratio of 3.7 to 1. These data, along with the deuterium and tritium kinetic isotope effects on hydride transfer, allow exact calculation of the intrinsic isotope effect and the forward and reverse commitments to catalysis, which have values of 5.1 +/- 0.8, 6.3 +/- 1.0, and 2.0 +/- 0.3, respectively. The viscosity dependence of the tritium isotope effect was measured, which allowed determination of the internal and external components of the commitment factors. The reverse commitment has no external portion, but the forward commitment can be divided into external and internal portions of 3.7 +/- 1.2 and 2.6 +/- 1.6, respectively. These data indicate that the reaction becomes committed to catalysis in the forward direction by formation of the Michaelis complex; reverse hydride transfer from NADH to OAA is twice as fast as decarboxylation of OAA, and recarboxylation of pyruvate occurs at a negligible rate. The rate constant for dissociation of OAA from the enzyme active site was estimated to be approximately 4 orders of magnitude slower than that for dissociation of oxaloglycolate, which is the product of the enzyme-catalyzed oxidation of (+)-tartrate. PMID- 8457549 TI - Binding of Ca2+ to calmodulin and its tryptic fragments: theory and experiment. AB - The Ca(2+)-binding constant of the protein calmodulin is determined experimentally at different pH and varying salt concentration. By comparison to statistical mechanical simulation results, it is shown that the shift in binding constant upon addition of salt is almost quantitatively due to electrostatic interactions. Specific interactions as well as effects due to structural rearrangements of the protein seem to be less important, indicating a structurally rather conserved protein upon addition of salt and changes in pH. The tryptic fragments of calmodulin also bind calcium with high affinity, and the electrostatic effects seem likewise to dominate the binding constant shifts in these systems. It is also shown that the chemical potential of free calcium ions, which is normally dominated by the salt, is strongly influenced by the highly charged calmodulin molecule. This complicates a detailed comparison at low salt concentration, since it requires very accurate information on the salt and protein concentrations, which normally are not available. PMID- 8457550 TI - Significance of hydrophobic S4-P4 interactions in subtilisin 309 from Bacillus lentus. AB - The subtilisins have an extended substrate binding cleft comprising at least 8 subsites. Two pockets at the S1 and S4 sites are particularly conspicuous, and the interactions between substrate and these two pockets are very important for the substrate specificity. Phe residues have mutationally been introduced at one of positions 102, 128, 130, and 132 of the subtilisin Savinase from Bacillus lentus to investigate the effects of introducing bulky groups along the rim of the S4 binding pocket. It is shown that the marked P4 preference of wild-type Savinase for aromatic groups is eliminated by the Gly102-->Phe and Ser128-->Phe mutations, indicating that bulky groups at positions 102 and 128 block the S4 binding site. In contrast, the activity toward hydrophilic P4 residues is not nearly as affected by these mutations, suggesting that the binding mode of the P4 side chain is dependent on its properties. Introduction of a bulky -CH2-S-CH2-CH2 pyridyl group at position 128, by mutational incorporation of Cys followed by chemical modification with 2-vinylpyridine, has essentially the same effect. The Ser130-->Phe mutation hardly affects the activity of the enzyme while the Ser- >Phe mutation at position 132 renders the preference for hydrophobic groups in P4 even more pronounced. This mutation furthermore affects the size of the S4 pocket. An analysis of double mutants at positions 132 and 104 suggests that the S4 region is flexible and is adjusted upon binding of substrates. PMID- 8457551 TI - Proton NMR of Escherichia coli sulfite reductase: the unligated hemeprotein subunit. AB - The isolated hemeprotein subunit of sulfite reductase (SiR-HP) from Escherichia coli consists of a high spin ferric isobacteriochlorin (siroheme) coupled to a diamagnetic [4Fe-4S]2+ cluster. When supplied with an artificial electron donor, such as methyl viologen cation radical, SiR-HP can catalyze the six electron reductions of sulfite to sulfide and nitrite to ammonia. Thus, the hemeprotein subunit appears to represent the minimal protein structure required for multielectron reductase activity. Proton magnetic resonance spectra are reported for the first time on unligated SiR-HP at 300 MHz in all three redox states. The NMR spectrum of high spin ferric siroheme at pH 6.0 was obtained for the purpose of comparing its spectrum with that of oxidized SiR-HP. On the basis of line widths, T1 measurements, and 1D NOE experiments, preliminary assignments have been made for the oxidized enzyme in solution. The pH profile of oxidized SiR-HP is unusual in that a single resonance shows a 9 ppm shift over a range of only 3 pH units with an apparent pK = 6.7 +/- 0.2. Resonances arising from the beta-CH2 protons of cluster cysteines have been assigned using deuterium substitution for all redox states. One beta-CH2 resonance has been tentatively assigned to the bridging cysteine on the basis of chemical shift, T1, line width, and the presence of NOEs to protons from the siroheme ring. The observed pattern of hyperfine shifts can be used as a probe to measure the degree of coupling between siroheme and cluster in solution. The cluster iron sites of the resting (oxidized) enzyme are found to possess both positive and negative spin density which is in good agreement with Mossbauer results on frozen enzyme. The NMR spectrum of the 1-electron reduced form of SiR-HP is consistent with an intermediate spin (S = 1) siroheme. Intermediate spin Fe(II) hemes have only been previously observed in 4-coordinate model compounds. However, the amount of electron density transferred to the cluster, as measured by the isotropic shift of beta-CH2 resonances, is comparable to that present in the fully oxidized enzyme despite diminution of the total amount of unpaired spin density available. Addition of a second electron to SiR-HP, besides generating a reduced S = 1/2 cluster with both upfield and downfield shifted cysteine resonances, converts siroheme to the high spin (S = 2) ferrous state.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8457552 TI - Solid-state NMR determination of intra- and intermolecular 31P-13C distances for shikimate 3-phosphate and [1-13C]glyphosate bound to enolpyruvylshikimate-3 phosphate synthase. AB - Rotational-echo, double-resonance (REDOR) 31P NMR was used to obtain internuclear distances for shikimate 3-phosphate (S3P) and N-(phosphonomethyl)-[1-13C]glycine (glyphosate) bound to 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase, a 46 kDa enzyme essential for the synthesis of aromatic amino acids in plants and microorganisms. An intermolecular 31P-13C distance of 7.2 A was measured between the phosphate of S3P and the labeled carbon of glyphosate. This means that S3P and glyphosate are in proximity in the binding site of the enzyme. An intramolecular 31P-13C distance of 5.6 A was measured between the phosphonate 31P and the labeled carbon of glyphosate. This distance can be achieved only if glyphosate is completely extended when bound to EPSP synthase. PMID- 8457553 TI - Formation and spectroscopic characterization of a novel monomeric cadmium- and phosphate-containing form of metallothionein. AB - The occurrence of a new monomeric cadmium and phosphate containing metallothionein (MT) form, i.e., Cd13-(Pi)2-MT, is reported. The preferential formation of this MT form from Cd7-MT has been shown to occur in the presence of phosphate and free cadmium at low protein concentration and elevated temperatures. This form displays in gel filtration an apparent molecular weight of 8,900 as opposed to 12,000 for Cd7-MT, suggesting the presence of a more globular structure. This new MT form was characterized by electronic absorption, by circular dichroism (CD), and by 1H, 31P, and 113Cd NMR spectroscopy. The Cd13 (Pi)2-MT form displays at least 24 113Cd signals between 240 and 520 ppm indicating (i) the absence of the original cluster structure of Cd7-MT, (ii) the participation of oxygen and/or nitrogen ligands besides thiolates in metal coordination, and (iii) the presence of more than one stable MT form in the sample. From homonuclear 113Cd COSY and CD studies, evidence for the existence of a cluster structure was obtained. It has been demonstrated that in the Cd13-(Pi)2 MT form two phosphate molecules are bound noncovalently and shown that a very slow exchange with [32P]phosphate in solution (half-life of approximately 56 h) takes place. In the 31P NMR studies, three 31P signals from protein-bound phosphate between 3.5 and 6 ppm have been observed. The 31P signal at 5.7 ppm displayed a heteronuclear 31P-113Cd coupling (J2 = 56 Hz) which provides evidence for direct metal-phosphate coordination. The structural and NMR features of this new MT form are discussed. PMID- 8457554 TI - Identification of cross-linked amino acids in the protein pair HmaL23-HmaL29 from the 50S ribosomal subunit of the archaebacterium Haloarcula marismortui. AB - 50S ribosomal subunits from the extreme halophilic archaebacterium Haloarcula marismortui were treated with the homobifunctional protein-protein cross-linking reagents diepoxybutane (4 A) and dithiobis(succinimidyl propionate) (12 A). The dominant product with both cross-linking reagents was identified on the protein level as HmaL23-HmaL29, which is homologous to the protein pair L23-L29 from Escherichia coli [Walleczek, J., Martin, T., Redl, B., Stoffler-Meilicke, M., & Stoffler, G. (1989) Biochemistry 28, 4099-4105] and from Bacillus stearothermophilus [Brockmoller, J., & Kamp, R. M. (1986) Biol. Chem. Hoppe Seyler 367, 925-935]. To reveal the exact cross-linking site in HmaL23-HmaL29, the cross-linked complex was purified on a preparative scale by conventional and high-performance liquid chromatography. After endoproteolytic fragmentation of the protein pair, the amino acids engaged in cross-link formation were unambiguously identified by N-terminal sequence analysis and mass spectrometry of the cross-linked peptides. The cross-link is formed between lysine-57 in the C terminal region of HmaL29 and the alpha-amino group of the N-terminal serine in protein HmaL23, irrespective of the cross-linking reagent. This result demonstrates that the N-terminal region of protein HmaL23 and the C-terminal domain of HmaL29 are highly flexible so that the distance between the two polypeptide chains can vary by at least 8 A. Comparison of our cross-linking results with those obtained with B. stearothermophilus revealed that the fine structure within this ribosomal domain is at least partially conserved. PMID- 8457555 TI - Oxygen binding by single crystals of hemoglobin. AB - Reversible oxygen binding curves for single crystals of hemoglobin in the T quaternary structure have been measured using microspectrophotometry. Saturations were determined from complete visible spectra measured with light linearly polarized parallel to the a and c crystal axes. Striking differences were observed between the binding properties of hemoglobin in the crystal and those of hemoglobin in solution. Oxygen binding to the crystal is effectively noncooperative, the Bohr effect is absent, and there is no effect of chloride ion. Also, the oxygen affinity is lower than that of the T quaternary structure in solution. The absence of the Bohr effect supports Perutz's hypothesis on the key role of the salt bridges, which are known from X-ray crystallography to remain intact upon oxygenation. The low affinity and absence of the Bohr effect can be explained by a generalization of the MWC-PSK model (Monod, Wyman, & Changeux, 1965; Perutz, 1970; Szabo & Karplus, 1972) in which both high- and low affinity tertiary conformations, with broken and unbroken salt bridges, respectively, are populated in the T quaternary structure. Because the alpha and beta hemes make different projections onto the two crystal axes, separate binding curves for the alpha and beta subunits could be calculated from the two measured binding curves. The approximately 5-fold difference between the oxygen affinities of the alpha and beta subunits is much smaller than that predicted from the crystallographic study of Dodson, Liddington, and co-workers, which suggested that oxygen binds only to the alpha hemes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457556 TI - Monitoring conformational change in the human erythrocyte glucose carrier: use of a fluorescent probe attached to an exofacial carrier sulfhydryl. AB - Several fluorescent sulfhydryl reagents were tested as probes for assessing substrate-induced conformational change of the human erythrocyte glucose carrier. Of these, 2-(4'-maleimidylanilino)-naphthalene-6-sulfonic acid (Mal-ANS) inhibited 3-O-methylglucose transport most strongly and specifically labeled a previously characterized exofacial sulfhydryl on the glucose carrier. Analysis of equilibrium cytochalasin B binding in cells treated with Mal-ANS suggested that the inhibition of transport was due to a partial channel-blocking effect, and not to competition for the substrate binding site or to hindrance of carrier conformational change. In purified glucose carrier prepared from cells labeled on the exofacial sulfhydryl with Mal-ANS, a blue shift in the peak of fluorescence indicated that the fluorophore was in a relatively hydrophobic environment. Mal ANS fluorescence in such preparations was quenched by ligands with affinity for the outward-facing carrier (ethylidene glucose, D-glucose, and maltose), but not by inhibitors considered to bind to the inward-facing carrier conformation (cytochalasin B or phenyl beta-D-glucoside). The effect of ethylidene glucose appeared to be related to an interaction with the glucose carrier, since the concentration dependence of ethylidene glucose-induced quench correlated well with the ability of the sugar analog to inhibit cytochalasin B binding to intact cells. The hydrophilic quenchers iodide and acrylamide decreased carrier-bound Mal-ANS fluorescence, resulting in downward-curving Stern-Volmer plots. Whereas ethylidene glucose enhanced iodide-induced quench, it had no effect on that of acrylamide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457557 TI - Polypyrimidine tracts and their binding proteins: regulatory sites for posttranscriptional modulation of gene expression. PMID- 8457558 TI - A point mutation at cysteine 189 blocks the water permeability of rat kidney water channel CHIP28k. AB - CHIP28k is an important water-transporting protein in the kidney proximal tubule and the thin descending limb of Henle [Zhang, Skach, Hasegawa, Van Hoek, & Verkman (1993) J. Cell Biol. 120, 359-369] that is homologous to human erythrocyte CHIP28 [Preston & Agre (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 11110 11114]. Oligonucleotide-directed mutagenesis was used to identify the cysteine(s) involved in inhibition of the water-transporting function of CHIP28k by the mercurial HgCl2. Each of the four cysteines (at positions 87, 102, 152, and 189) were mutated to serine individually, or in combinations. In vitro transcribed cRNA was expressed in Xenopus oocytes for measurement of osmotic water permeability (Pf) in the absence or presence of 0.3 mM HgCl2. Pf (in cm/s x 10( 4) measured at 10 degrees C) was 7 +/- 1 in water-injected oocytes. In wild-type CHIP28k, Pf was 58 +/- 7 (-HgCl2) and 12 +/- 1 (+HgCl2). Mutation of cysteine 87, 102, or 152, individually or in combinations, had little effect on oocyte Pf or on the inhibition by HgCl2. Mutation of cysteine 189 to serine or glycine gave similar Pf values of 49-56 (-HgCl2); however, Pf was not inhibited up to 1 mM HgCl2. Mutation of cysteine 189 to the larger amino acid tryptophan gave a low Pf of 9 +/- 1; coexpression with wild-type CHIP28k indicated that the tryptophan mutation was not dominant negative. Mutation of the asparagine 42 and 205 glycosylation sites to threonine had little effect on Pf.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457559 TI - Chemical compensation in macromolecular bridge-binding to thrombin. AB - The binding energetics of eight synthetic peptides capable of interfering with thrombin function have been studied by steady-state measurements and clotting assays. The synthetic peptides are bifunctional inhibitors consisting of three domains: (i) a fragment of the C-terminus of recombinant hirudin, hir55-65, which binds to the fibrinogen-recognition site of thrombin; (ii) a small active site inhibitor, Ac-(DF)PRP, binding to the catalytic pocket of the enzyme, and (iii) a linker spanning these two portions with variable length and chemical composition. All these synthetic peptides are competitive inhibitors of fibrinogen. On the other hand, a linker of at least 13 carbon atoms is required for full competitive inhibition of the hydrolysis by thrombin of small synthetic substrates, which only bind to the catalytic pocket of the enzyme. The best inhibitory effect is observed with a linker of 13 carbon atoms, with a value of KI in the nanomolar range. Studies conducted as a function of temperature, in the range 15-40 degrees C, have revealed the enthalpic and entropic components of inhibitor binding to thrombin. Chemical compensation is observed for all synthetic peptides that bridge-bind to the fibrinogen-recognition site and the catalytic pocket of the enzyme thereby inhibiting in a competitive fashion either fibrinogen binding or the hydrolysis of small synthetic substrates. The extrathermodynamic relationship between delta H and delta G also includes the enthalpy and free energy of binding for the natural substrate fibrinogen and the potent natural inhibitor hirudin, measured under identical solution conditions. Preferential binding of hirudin over fibrinogen is an entropy-driven process.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457560 TI - Conservation of a helix-stabilizing dipole moment in the PP-fold family of regulatory peptides. AB - Investigation of the charge distribution for all known members of the PP-fold family of peptides reveals a common pattern characterized by a cluster of negative charges in the beta-turn region and a cluster of positive charges in the receptor-binding region of the peptide. Detailed analysis of the electrostatic properties of five representative members of the PP-fold family of peptides (human neuropeptide Y, human peptide YY, human pancreatic polypeptide, avian PP, and lamprey peptide methionine tyrosine) shows that this characteristic charge clustering gives rise to a common dipole moment of 325-450 D directed from the beta-turn region toward the receptor-binding region. This overall dipole moment is antiparallel to the dipole moment of the alpha-helix caused by alignment of the peptide dipoles parallel to the helix. Calculations of the stabilization energy for this antiparallel dipole moment arrangement were performed in two ways: (1) by the use of a Poisson-Boltzmann approach which allows for an estimate of the screening effect, and (2) by the use of a uniform dielectric model (Coulomb's law). It is found that the alpha-helix is stabilized by approximately 5-10 kcal/mol due to electrostatic forces alone when the screening effect is considered. This energy is of the same order of magnitude as the enthalpy change for the unfolding of avian PP (approximately 30 kcal/mol), strongly indicating that the charge-dipole interactions are of significant importance for the stability of the three-dimensional structure of the PP-fold peptides. PMID- 8457561 TI - Inhibition of the fusion-inducing conformational change of influenza hemagglutinin by benzoquinones and hydroquinones. AB - Influenza hemagglutinin (HA) undergoes a conformational change that is required for viral entry. The rearrangement includes exposure of the fusion peptide, a hydrophobic segment buried in the trimer interface of the native protein. Since fusion peptide release triggers the membrane fusion event crucial for viral replication, inhibition of fusion peptide exposure should prevent infection. We reasoned that small molecules that bind to HA and stabilize its nonfusogenic conformation would block viral activity. A computer-assisted method was used to select putative HA ligands. One of the selected compounds, 4A,5,8,8A-tetrahydro 5,8-methano-1,4-naphthoquinone, prevented the conversion of X31 HA to a conformation recognized by alpha-fusion peptide antisera. Several derivatives of this compound, including both benzoquinones and hydroquinones, also showed inhibition. The most effective compounds tested have IC50S between 1 and 20 microM. Representative compounds also inhibited virus-induced syncytia formation, HA-mediated hemolysis, and viral infectivity in vitro. The inhibitors are attractive leads for the development of antiviral drugs and can serve as probes of the mechanism of the conformational change of HA. PMID- 8457562 TI - Binding of 4',6-diamidino-2-phenylindole (DAPI) to AT regions of DNA: evidence for an allosteric conformational change. AB - The interaction of 4',6-diamidino-2-phenylindole (DAPI) with several double helical poly- and oligonucleotides has been studied in solution using optical spectroscopic techniques: flow linear dichroism (LD), induced circular dichroism (CD), and fluorescence spectroscopy. In AT-rich sequences, where DAPI is preferentially bound, LD indicates that the molecule is edgewise inserted into the minor groove at an angle of approximately 45 degrees to the helix axis. This binding geometry is found for very low as well as quite high binding ratios. The concluded geometry is in agreement with that of the DAPI complex in a crystal with the Drew-Dickerson dodecamer, and the DAPI complex with this dodecamer in solution is verified to have an ICD spectrum similar to that of the complex with [poly(dA-dT)]2 at low binding ratios. The observation of two types of CD spectra characteristic for the binding of DAPI to DNA, and also for the interaction with [poly(dA-dT)]2, demonstrates that the first binding mode, despite its low apparent abundance (a few percent), is not due to a specific DNA site. The effect may be explained in terms of an allosteric binding such that when DAPI molecules bind contiguously to the AT sequence the conformation of the latter is changed. The new conformation, which according to LD appears to be stiffer than normal B form DNA, is responsible for the second type of induced CD spectrum in the DAPI chromophore. Although the spectroscopic results indicate a change of DNA conformation, consistent with an allosteric binding model, they do not explicitly require any cooperativity, but accidental neighbors could also explain the data. PMID- 8457563 TI - Triplex formation by oligodeoxyribonucleotides involving the formation of X.U.A triads. AB - The stabilities of oligodeoxyribonucleotide triplexes containing a single pyrimidine-purine base pair, which interrupts an otherwise purine-pyrimidine base pair motif, were studied by UV melting experiments. The oligomer systems consisted of an oligodeoxyribonucleotide target duplex d-GAAGAAAAAAYAAAA/d TTTTZTTTTTTCTTC, I.II(Y.Z), or d-GAAGAAAAAGUGAAA/d-TTTCACTTTTTCTTC, IV.V(U.A), where Y.Z is C.G, T.A, or U.A and U is deoxyuridine. The third strand oligodeoxyribopyrimidine was d-CTTCTTTTTTXTTTT, III(X), or d-CTTCTTTTTCXCTTT, VI(X), where C is 5-methyldeoxycytidine. Triplexes were observed in the system III.I.II(X.C.G) when X was T or U. This may involve formation of T. or U.C.G triads in which the 4-carbonyl of T or U serves as a hydrogen bond acceptor for the N4-amino group of C. Triplex formation between III(X) and I.II(T.A) was only observed when X was G. In contrast to T.A or C.G, it appears a U.A base pair in the duplex target is a much more versatile participant in triad formation. Thus, stable triplexes were observed in III.I.II(X.U.A) and in VI.IV.V(X.U.A) when X was C, C, T, or U. The formation of a T.U.A or U.U.A triad can occur if the T or U of III translates approximately 1.4 A into the major groove, thereby allowing the 3-NH of T or U to donate a hydrogen bond to the 4-carbonyl oxygen of U in the duplex. Formation of C. or C.U.A base triads could involve formation of a single hydrogen bond between the third strand N4-amino group of C or C and the 4 carbonyl group of U of the target.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457564 TI - Human factor VIIa and its complex with soluble tissue factor: evaluation of asymmetry and conformational dynamics by ultracentrifugation and fluorescence anisotropy decay methods. AB - Ultracentrifugation and fluorescence anisotropy decay measurements were used to evaluate the asymmetry and conformational dynamics of human blood clotting enzyme VIIa (VIIa) and the complex it forms with a soluble truncation mutant of human tissue factor (sTF) which acts as an essential cofactor for VIIa. Sedimentation velocity experiments showed that both VIIa and the sTF.VIIa complex are highly asymmetric. In each case, the friction ratio f/fsphere, is consistent with a family of general elliposids ranging from prolate to oblate. Fluorescence anisotropy decay experiments were used to limit the family of elliposids which can describe the hydrodynamic behavior of VIIa and sTF.VIIa. For both VIIa and the sTF.VIIa complex, the oblate ellipsoid of revolution was eliminated. In addition, the fluorescence anisotropy decay data clearly show that upon binding sTF.VIIa loses a segmental motion involving a domain containing the active site of the enzyme. This suggests that sTF causes a stabilization of a limited range of VIIa conformations. This stabilization may be important for proper recognition of the TF.VIIa substrate, factor X. PMID- 8457565 TI - Replication of the base pair 6-thioguanine/5-methyl-2-pyrimidine with the large Klenow fragment of Escherichia coli DNA polymerase I. AB - The kinetics and the fidelity of replication of the base pair 6-thioguanine (Gs)/5-methyl-2-pyrimidinone (Th) have been determined by using defined oligomers with the large Klenow fragment of Escherichia coli DNA polymerase I. The insertion efficiency, Vmax/Km (min-1 microM-1), of Th opposite Gs is 1.5 and the insertion efficiency of Gs opposite Th is 0.7. By comparison, the insertion efficiencies of C opposite G and G opposite C are 0.5 and 1.5. The insertion efficiency of the next base, A opposite T, is 2 times greater after the base pair Gs/Th than after G/C. The fidelity of replication with respect to thymine and adenine has misinsertion frequencies, or ratios of the insertion efficiency of the "wrong" base to the "right" base, of 7 x 10(-4) for T opposite Gs (T/Gs), 4 x 10(-6) for T/Th, and a maximum stable misinsertion frequency of 4 x 10(-4) for A/Th. No detectable elongation occurs after an A is inserted opposite a Gs. These values are similar to the misinsertion frequencies of G and C with T and A. The maximum stable misinsertion frequencies with G and C are 4 x 10(-2) for G/Th, 3 x 10(-2) -7 x 10(-3) for Gs/C, and 2.6 x 10(-1) for C/Gs, and the misinsertion frequency is < 1 x 10(-3) for Th/G. The kinetics results and molecular modeling suggest modifications to the Gs/Th base pair that may provide higher levels of fidelity of replication with respect to C and G. PMID- 8457566 TI - Thermodynamics of binding of the CO2-competitive inhibitor imidazole and related compounds to human carbonic anhydrase I: an isothermal titration calorimetry approach to studying weak binding by displacement with strong inhibitors. AB - The visible spectrum of Co(II)-substituted human carbonic anhydrase I (HCA I) complexed with the unique CO2-competitive inhibitor imidazole undergoes a marked alkaline intensification, with a midpoint near pH 8 [Bauer, R., Limkilde, P., & Johansen, J. T. (1977) Carlsberg Res. Commun. 42, 325-339]. This change was first attributed to the ionization of a nondisplaced water ligand of the active-site metal in a five-coordinate complex. Later proposals favored assigning it to the deprotonation of the bound imidazole itself to give a tetrahedrally coordinated imidazolate anion at high pH. We have determined by isothermal titration calorimetry the pH dependence of the enthalpy of binding of imidazole and its analogues to HCA I and Co(II)HCA I. We devised an indirect strategy whereby the enthalpy of binding of the strong sulfonamide inhibitor methazolamide was determined in the absence and presence of a constant high concentration of the competing imidazole or its analogues. The standard enthalpy of binding of deprotonated methazolamide to the "acid" form of HCA I and Co(II)HCA I was found to be pH independent over the pH range of 6.5-9.5, as expected. It was also identical for both the zinc (-13.5 +/- 1.1 kcal M-1) and the cobalt (-13.7 +/- 0.4 kcal M-1) forms. The standard enthalpy of binding of neutral imidazole (average value -6.1 +/- 0.8 kcal M-1) surprisingly did not show any marked pH dependence, varying by about 1.1 and 2.6 kcal M-1 for the zinc and cobalt enzymes, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457567 TI - Fluorescence quenching in a strongly helical peptide series: the role of noncovalent pathways in modulating electronic interactions. AB - The very strong helical propensity of peptides rich in alpha-aminoisobutyric acid (Aib) has enabled the design of a set of helices containing as guest amino acids one fluorescent chromophore, beta-(1'-naphthyl)-L-alanine, and one heavy atom perturber, p-bromo-L-phenylalanine. The fluorescence of the chromophoric residue was monitored in this set to explore heavy atom induced enhanced intersystem crossing as a potentially useful tool for exploring remote electronic interactions in biomolecules. The peptides in this set were sequence isomers of each other and were designed such that the chromophore and the perturber were separated by two, one, or zero Aib residues. The respective distances between the aromatic side chains are then modulated by the twist of the helix. All peptides showed steady-state fluorescence quenching, and on the basis of further time resolved triplet-triplet absorption experiments, two mechanisms for the heavy atom induced fluorescence quenching were established: (i) a weak and nominally spin-forbidden singlet-triplet energy transfer and (ii) the remote heavy atom effect (RHAE) on the intersystem crossing within the fluorophore. Both the rate of singlet-triplet energy-transfer and the RHAE are at their maxima in the peptide with the largest sequence separation but the smallest direct distance between the chromophore and the perturber. Thus neither quenching mechanism is controlled by the length of the intervening covalent pathway. Subtle factors arising from the structure of the intervening peptide backbone apparently contribute to the RHAE for the peptides with shorter sequence separation. Because the sensitivity to the remote heavy atom is a measure of electronic delocalization, this result may have significance for the understanding of the role of helices in biological electron-transfer interactions. PMID- 8457568 TI - Affinity labeling of lecithin retinol acyltransferase. AB - Lecithin retinol acyltransferase (LRAT) transfers acyl groups regiospecifically from the sn-1 position of lecithins to all-trans-retinol (vitamin A) and similar retinoids. LRAT is essential for the biosynthesis of 11-cis-retinal, the visual pigment chromophore. LRAT is also required for the general dietary mobilization of vitamin A. The enzyme is membrane-bound and has been solubilized and partially, but not completely, purified. It is demonstrated here that all-trans retinyl alpha-bromoacetate (RBA) is a potent irreversible affinity labeling agent of LRAT. The measured KI = 12.1 microM and the pseudo-first-order rate constant for inhibition is kinh = 8.2 x 10(-4) s-1. The specificity of the inhibition process is further evidenced by the observation that alpha-bromoacetate derivatives of hydrophobic alcohols which are not substrates for LRAT, such as cholesterol and beta-ionol, are not inhibitors of the enzyme. Labeling of the partially purified enzyme with 3H-RBA showed a single radiolabeled band of molecular weight approximately 25,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. PMID- 8457569 TI - Evidence for two pools of cholesterol in the Acholeplasma laidlawii strain B membrane: a deuterium NMR and DSC study. AB - Recent investigations have indicated that there exists a well-defined range of membrane hydrocarbon order compatible with good growth of the microorganism Acholeplasma laidlawii B [Monck, M., Bloom, M., Lafleur, M., Lewis, R. N. A. H., McElhaney, R. N., & Cullis, P. R. (1992) Biochemistry 31, 10037-10043]. Since cholesterol increases hydrocarbon order in membranes, it was of interest to examine the effect of cholesterol on the hydrocarbon order and growth characteristics of A. laidlawii B. Cholesterol is normally absent from A. laidlawii membranes since it is neither biosynthesized nor required for the growth or survival of the microorganism. However, cholesterol will be incorporated into the membrane if exogenously supplied to the A. laidlawii culture. For membranes prepared from cells grown in the presence of cholesterol, chemical determinations indicated cholesterol represented as much as 40 mol% of the total membrane lipid. However, 2H NMR order parameter measurements and DSC studies of the same membrane preparation suggested that cholesterol was present at significantly lower levels (approximately 10-15 mol%) in the membrane lipid bilayer. Further incorporation of cholesterol into the A. laidlawii lipid bilayer was found to occur with an increase in temperature or by lyophilization and rehydration at high temperatures, suggesting that sterol present in a separate pool in the membrane preparation could then gain access to the bilayer. 2H NMR spectra of A. laidlawii membrane preparations containing deuterium-labeled cholesterol indicate that the bulk of the cholesterol present in this separate pool is in a solid form. PMID- 8457570 TI - Roles of cysteines in human lecithin:cholesterol acyltransferase. AB - Human lecithin:cholesterol acyltransferase (LCAT, E.C.2.3.1.43) is a serine-type esterase that contains six cysteines, two of which, Cys31 and Cys184, are free. The remaining cysteines form disulfide links. One of these is between Cys50 and Cys74 and the other is between Cys313 and Cys356. The cDNA of LCAT and mutants in which one or two of the six cysteines were replaced by glycine was expressed in COS-6 cells. Polymerase chain reactions and Northern blot analysis indicated that LCAT mRNA was produced by all transfectants. Western blots of all transfected cells probed with a polyclonal antibody revealed intracellular LCAT. Substitution of glycine for either Cys50, Cys74, Cys313, or Cys356 was associated with a nearly total absence of activity in the medium. No protein was secreted when glycine replaced either of the amino acid residues that link Cys313 and Cys356. The small amounts of the Cys50-->Gly and Cys74-->Gly mutants found in the medium had specific activities that were much lower than that of the wild-type LCAT. All other transfectants secreted immunologically measurable amounts of active enzyme. Mutants in which one or both free cysteines, Cys31 and Cys184, were replaced with glycine were less active than the wild type and only partially inhibited by a sulfhydryl blocking reagent. The substrate specificities of the Cys31-->Gly and Cys184-->Gly mutants differed from that of the wild type.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457571 TI - Sensitive fluorescence-based thermodynamic and kinetic measurements of DNA hybridization in solution. AB - Kinetic and thermodynamic constants associated with DNA hybridization were determined in solution using fluorescence measurements and complementary fluorophore-labeled oligomers. One oligomer was labeled with a 5'-terminal fluorescein, and the other was labeled with a 3'-terminal rhodamine. The juxtaposition of the two labels in double-stranded complexes results in a strong quenching of the fluorescein emission, thereby providing the means for distinguishing single-stranded DNA from double-stranded DNA. Since measurements were based on fluorescence, DNA denaturation and association could be monitored routinely at strand concentrations 100-1000-fold lower than permitted by absorbance hypochromicity measurements. To determine if fluorescence quenching mirrored base pair formation, temperature profiles of DNA association and dissociation were constructed from both absorbance hypochromicity and fluorescence quenching measurements at a number of different DNA concentrations. Analyses of these profiles using the "all-or-none" model of hybridization provided thermodynamic data which were statistically indistinguishable between the two measurement methods, thus validating the use of fluorescence quenching in thermodynamic studies of oligomers. The effects of fluorophore attachment on the thermodynamic properties of the DNA strands were investigated by analyzing the melting curves of different combinations of unlabeled and labeled complementary oligomers. The presence of both labels was found to stabilize the double-stranded DNA by about -1.5 kcal in delta G degrees 298, primarily due to the fluorescein label. Association and dissociation rate constants were determined by fluorescence measurements at different temperatures, and linear Arrhenius plots were obtained. The fluorescence measurements provided a unique "label dilution" method for measuring dissociation rate constants of oligomers based upon the dynamic association and dissociation of complementary DNA strands at constant temperature. Association rate measurements were simplified since relatively low concentrations of complementary oligomers could be mixed, thereby reducing hybridization rates and eliminating the need for rapid mixing and measurement techniques. PMID- 8457572 TI - Interaction of peptide fragment 828-848 of the envelope glycoprotein of human immunodeficiency virus type I with lipid bilayers. AB - The interaction of the peptide fragment 828-848, called P828, from the carboxy terminal region of the envelope glycoprotein gp41 of HIV-I with model membranes composed of phosphatidylcholine (PC) and phosphatidylglycerol (PG) was investigated using microelectrophoretic mobility of liposomes, fluorescence polarization of labeled lipids, NMR, and differential scanning calorimetry. The peptide binds to negatively charged lipid surfaces. No interaction between P828 and neutral PC surfaces is observed. The interaction between the peptide and the lipid is exclusively electrostatic with the six positively charged arginines of P828 acting as binding sites for PG. Circular dichroism measurements of P828 indicate that the peptide undergoes a transition from a random coil to an ordered conformation upon binding to negatively charged PG bilayers or SDS micelles, but not in the presence of neutral PC bilayers. The ordered structure has an apparent helical content of 60%. IN DOPG/DOPC mixtures containing 20 mol % DOPG, the peptide causes the formation of lipid domains enriched in DOPG, as assessed by measurement of fluorescence energy transfer between labeled PG and PC. The formation of these domains requires energy and therefore reduces the strength of peptide binding to the lipid matrix. Our data support and quantitate the results from antibody binding studies [Haffar, O.K., Dowbenko, D. J., & Berman, P. W. (1988) J. Cell Biol. 107, 1677-1687] that the carboxy-terminal segment of the envelope glycoprotein gp41 interacts with microsomal membranes. PMID- 8457573 TI - Interaction of the 47-residue antibacterial peptide seminalplasmin and its 13 residue fragment which has antibacterial and hemolytic activities with model membranes. AB - The interaction of seminalplasmin (SPLN), a 47-residue antibacterial peptide, and its 13-residue fragment (SPF), which has antibacterial and hemolytic activities, with model membranes has been investigated. The fluorescence characteristics of the single Trp residue in these peptides indicate strong binding to lipid vesicles. SPLN binds more strongly to dioleoylphosphatidylglycerol vesicles compared to dioleoylphosphatidylcholine and phosphatidylserine vesicles. Localization studies using fluorescence quenchers like NO3-, I-, and acrylamide indicate that the Trp residues in both of the peptides are located away from the head group region and are associated with the hydrophobic core. Both peptides cause release of carboxyfluorescein from zwitterionic as well as anionic vesicles. The biological activities of SPLN and SPF have been rationalized in terms of lipid-peptide interactions. It is proposed that the specificity in biological activity arises due to differences in the manner in which the peptides associate with the bacterial and red blood cell surfaces. PMID- 8457574 TI - Role of the charge pair aspartic acid-237-lysine-358 in the lactose permease of Escherichia coli. AB - Using a lactose permease mutant devoid of Cys residues (C-less permease), Asp237 and Lys358 were replaced with Cys or other amino acids to pursue the proposal that the two residues form a charge pair [King, S. C., Hansen, C. L., & Wilson, T.H. (1991) Biochim. Biophys. Acta 1062, 177-186]. Individual replacement of Asp237 with Cys, Ala, or Lys or replacement of Lys358 with Cys, Ala, or Asp virtually abolishes active lactose transport. However, simultaneous replacement of both residues with Cys and/or Ala yields permease with high activity. Therefore, neutral amino acid substitutions at either position are detrimental only because they leave the opposing charge unpaired. Strikingly, moreover, when Asp237 is interchanged with Lys358, high activity is observed. The results indicate strongly that Asp237 and Lys358 interact to form a salt bridge and that neither residue nor the salt bridge per se is important for activity. Immunoblots reveal low membrane levels of the active mutants lacking the putative salt bridge, suggesting a role for the salt bridge in either permease folding or stability and raising the possibility that the salt bridge may exist in a folding intermediate but not in the mature protein. Remarkably, however, a mutant with Cys in place of Asp237 is restored to full activity by carboxymethylation which recreates a negative charge at position 237. Pulse-chase analysis and heat inactivation studies indicate that the stability of the double mutant with Cys at positions 237 and 358 is comparable to C-less. Therefore, the interaction between Asp237 and Lys358 is likely to be important for permease folding and is maintained in the mature protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457575 TI - ATP-dependent aminophospholipid translocation in erythrocyte vesicles: stoichiometry of transport. AB - Vesicles released from human red blood cells by incubation with a suspension of sonicated dimyristoylphosphatidylcholine were purified by gel filtration. Purified vesicles and intact red cells had a very similar composition with respect to phospholipids and integral membrane proteins, but spectrin, the major component of the membrane skeleton, was not found in vesicles. Comparison of red cell and vesicle ATP levels (expressed as micromolar ATP per millimolar hemoglobin) showed a marked difference with a reduced content of only about 30% in vesicles, whatever the initial concentration in the erythrocytes. Spin-labeled aminophospholipids (phosphatidylserine and phosphatidylethanolamine) were translocated to the inner vesicle membrane layer at a comparable rate as in intact red cells provided that vesicles contained enough ATP. The maximum fraction of spin-labeled phospholipids translocated to the inner membrane layer was 84% for phosphatidylserine, 65% for phosphatidylethanolamine, 20-40% for phosphatidylcholine, and below 20% for sphingomyelin. The apparent Km of translocation, expressed as percent of total membrane phospholipid, was 0.14% for spin-labeled phosphatidylserine and 1.19% for spin-labeled phosphatidylethanolamine. This compares well to values established earlier for intact red blood cells. The fact that no ATP was synthesized in vesicles allowed determination of ATP consumption by aminophospholipid transport. The basic ATP hydrolysis rate was increased upon the addition of labeled aminophospholipids but not of labeled phosphatidylcholine or sphingomyelin. The stoichiometry between lipid translocation and ATP consumption, calculated from the respective initial velocities, was 1.13 +/- 0.2 for phosphatidylserine and 1.11 +/- 0.16 for phosphatidylethanolamine. PMID- 8457576 TI - Secondary structure and temperature behavior of the acetylcholine receptor by Fourier transform infrared spectroscopy. AB - Fourier transform infrared spectroscopy (FT-IR) was used to test the secondary structure of purified acetylcholine receptor membranes from Torpedo californica. The secondary structure was estimated using the spectral features observed in the structure sensitive region of amide I and amide I' (between 1600 and 1700 cm-1), taking advantage of Fourier self-deconvolution and second-derivative techniques along with least-squares band fitting procedures. At least six different amide I' band components could be resolved in D2O and were tentatively assigned to beta structures (1680 and 1636 cm-1), alpha-helices (1657 cm-1), aperiodic structures and/or distorted helices (1646-1648 cm-1), and turns (1690 and 1668 cm-1), respectively. The beta-band around 1637 cm-1, in particular, turned out to be complex since it reproducibly exhibited weak features near 1630 and 1627 cm-1, thereby suggesting the presence of different chain interacting beta-structures. The band near 1657 cm-1 was assigned to alpha-helices which transverse the membrane bilayers, while 1646-1648-cm-1 component was tentatively attributed to aperiodic structures and alpha-helices localized within the "globular head" of the receptor protein protruding from the membrane surface into the surrounding water. Least-squares band fitting procedures were applied in order to estimate relative amounts of secondary structures. The results suggest 36-43%, 32-33%, 14 24%, and 18-19% for beta-, alpha-helical, turn, and "rest" structures, respectively. Additionally, the temperature- and time-dependent variations of the secondary structure was tested by evaluating the changes of amide I and amide II band components of receptor membranes dispersed in H2O and D2O.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457577 TI - Surface chemistry of binary mixtures of phospholipids in monolayers. Infrared studies of surface composition at varying surface pressures in a pulmonary surfactant model system. AB - Phospholipid monomolecular films at the air/water interface were studied using Langmuir-Blodgett (L-B) surface chemistry, 31P NMR spectroscopy, and infrared (IR) spectroscopy. These monolayers were composed of binary mixtures of acyl chain perdeuterated 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (i.e., DPPC-d62) with 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol (i.e., DPPG). This particular PC-PG binary mixture was chosen for study since this lipid system has been used as a model for pulmonary surfactant, especially in conjunction with the so-called "squeezing-out" hypothesis of pulmonary mechanics. This theory predicts that upon successive compression-expansion cycles, a surfactant surface film will reorganize to exclude all components except DPPC, thus resulting in a stable, low surface tension film. Several general results were obtained from these experiments. First, we have developed a combined spectroscopic assay using high resolution 31P NMR spectroscopy in combination with the C-H and C-D vibrational intensities obtained from the IR spectroscopy of binary mixtures in which one component is acyl chain perdeuterated. Using attenuated total reflectance IR spectroscopy of transferred L-B films, this combined spectroscopic approach allows us to quantitatively describe the fractional composition of each component in the binary monomolecular film. Second, when these methods are applied to transferred monolayer films of DPPC-d62 and DPPG (at an initial PC:PG mole ratio of 7:1), we find no evidence for a "squeezing-out" of the DPPG monolayer component at high surface pressure resulting in an enrichment of the DPPC component in the transferred monolayer film.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457578 TI - Disulfide bond contribution to protein stability: positional effects of substitution in the hydrophobic core of the two-stranded alpha-helical coiled coil. AB - To investigate the positional effect of the disulfide bond on the structure and stability of a two-stranded alpha-helical coiled-coil, an interchain disulfide bond was systematically introduced into the hydrophobic core of a de novo designed model coiled-coil at the N-terminus (position 2), C-terminus (position 33), and nonterminal positions a (positions 9, 16, 23, and 30) and d (positions 5, 12, 19, and 26). The rate of formation of a disulfide bond is faster at position d compared to at the corresponding position a under nondenaturing conditions, suggesting that position d is more suitable for engineering a disulfide bond. The structure and stability of the reduced and oxidized coiled coils were determined by circular dichroism studies in the absence and presence of guanidine hydrochloride. Our results demonstrate that the improvement of protein stability by introduction of a disulfide bond is very relevant to its location and the most effective disulfide bonds are those that can be introduced in the hydrophobic core without any disruption of the protein structure. The disulfide bond at position d with near-optimal geometry does not perturb the coiled-coil structure and makes the largest contribution to coiled-coil stability. In contrast, the inappropriate geometry of the disulfide bond at nonterminal position a introduces a high strain energy on the disulfide bond which disrupts the coiled-coil structure. At positions a, the closer the disulfide bridge is to the center of the coiled-coil, the larger the disruption on the coiled-coil structure and the smaller the contribution the disulfide bond makes to coiled-coil stability. The computer modeling results also suggest that an insertion of an interchain disulfide bond at position a in the GCN4 leucine zipper X-ray structure has a higher potential energy than insertion at position d. The energy-minimized coiled-coil structure with an interchain disulfide bond at position a has a larger root mean square difference from the X-ray structure of GCN4 than the coiled-coil with a disulfide bond at position d. Because interhelical interactions are common in globular proteins as well as coiled coils, the results obtained in this study will have general utility for selecting the sites for engineering disulfide bonds between alpha-helices. PMID- 8457579 TI - Parameters for evaluation and treatment of patients with cleft lip/palate or other craniofacial anomalies. American Cleft Palate-Craniofacial Association. March, 1993. PMID- 8457580 TI - The mechanisms by which mild respiratory chain inhibitors inhibit hepatic gluconeogenesis. AB - (1) Liver cells from starved rats were incubated with 10 mM L-lactate, 1 mM pyruvate and 0.3 microM glucagon in the presence and absence of the mild respiratory inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) at 0.5 mM. (2) The whole cell concentrations of phosphoenolpyruvate, 2-phosphoglycerate and 3-phosphoglycerate increased about 2-fold, whilst the triose and hexose phosphate concentrations all decreased significantly. Similar results were obtained with 0.15 microM oligomycin and 10 microM atractyloside. (3) These data can be explained by a substantial decrease in the cytosolic free concentration ratio of ATP/ADP acting on the equilibrium of glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate kinase. (4) The increase in cytosolic phosphoenolpyruvate concentration can account for the observed increase in pyruvate kinase flux that occurs under these conditions (Pryor et al. (1987) Biochem. J. 247, 449-457). (5) An inhibition of pyruvate carboxylase was also implied by a decrease in calculated tissue oxaloacetate concentrations, confirming a role for both enzymes in the inhibition of gluconeogenesis. (6) Whole cell concentrations of effectors of pyruvate carboxylase activity were measured; only the ATP/ADP ratio decreased significantly. (7) Subcellular fractionation studies showed a good correlation between the measured mitochondrial ATP/ADP ratio and rates of gluconeogenesis both in the presence and absence of oleate. (8) A similar correlation could be observed between rates of pyruvate carboxylation and the measured matrix ATP/ADP ratio in isolated liver mitochondria from starved rats. (9) Data are also presented suggesting an additional effect of DCMU on the rate pyruvate carboxylation in situ under some circumstances, mediated by decreases in mitochondrial acetyl-CoA and cytosolic pyruvate concentrations. (10) It is noted that the effects of phenylethylbiguanide (phenformin) on the rate of gluconeogenesis and metabolite profiles in the perfused liver (Cooke et al. (1973) J. Biol. Chem. 248, 5272-5277) are similar to those caused by DCMU, supporting a mitochondrial locus of action for this hypoglycaemic agent. PMID- 8457581 TI - Reaction mechanism of the reconstituted tricarboxylate carrier from rat liver mitochondria. AB - Transport of citrate and malate by the tricarboxylate carrier from rat liver mitochondria has been studied in a reconstituted system. Homologous citrate/citrate antiport and heterologous (electroneutral) citrate/malate antiport was kinetically analyzed. The maximal rates of the two exchange modes did not vary significantly within pH 7.0 to 7.8 which is the optimum pH-range for transport activity. On the other hand, the apparent transport affinity varied considerably within this range. Calculations on the basis of the different pK values for citrate and malate indicate that only H-citrate2- and malate2- are accepted as transport species by the tricarboxylate carrier. A complete set of half-saturation constants was established for citrate and malate on both the external and the internal side of the membrane. Both the Km and Vmax for citrate and malate were independent of the nature of the countersubstrate at the other side of the membrane. Bisubstrate initial velocity analyses of the exchange reaction resulted in a kinetic pattern which is consistent with a sequential antiport mechanism. This type of mechanism implies formation of a ternary complex of the carrier with two substrate molecules before the transport reaction occurs. Thus the tricarboxylate carrier falls into the functional family of mitochondrial carrier proteins showing sequential transport mechanisms. PMID- 8457582 TI - The function of ATP/ADP translocator in the regulation of mitochondrial respiration during development of heart ischemic injury. AB - Inhibitor titration studies were carried out in order to quantify the amount of control exerted by ATP/ADP translocator on the rate of succinate, palmitoylcarnitine + malate and pyruvate + malate oxidation in ischemia-damaged heart mitochondria. It was shown that after 30 min of total ischemia in vitro the maximal value of the control coefficient of the translocator was as high as in the control: 0.5-0.72 (succinate), 0.8-0.87 (palmitoylcarnitine + malate), 0.83 0.95 (pyruvate+malate). However, the translocator-controlled range of respiratory rates of ischemic mitochondria was narrower than that of normal mitochondria. The control coefficient of the translocator close to State 3 and State 4 was equal to 0-0.15. After 45 min ischemia the maximal value of the translocator control coefficient decreased by 25-30% in comparison with normal mitochondria with all substrates investigated. This value was preserved within a wide range of mitochondrial respiratory rates including the maximal rate in State 3. It was found that the amount of ATP/ADP translocator in mitochondria decreased by 20% after only 45 min ischemia. Our data show that the ATP/ADP translocator is one of the most important steps in regulation of oxidative phosphorylation in isolated mitochondria during development of heart ischemic injury. PMID- 8457583 TI - Linear dichroism and molecular orientation in Langmuir-Blodgett films of plastoquinones and alpha-tocopherol quinone. AB - The linear dichroism of monolayers of plastoquinone-9, plastoquinone-3 and alpha tocopherol quinone has been measured. The angle between the transition moments and the plane of the solid support was found to lie between 24 degrees and 28 degrees for the investigated prenylquinones. The possible orientation of quinone rings in a monolayer state has been discussed. PMID- 8457584 TI - Inactivation of phenobarbital-inducible rabbit-liver microsomal cytochrome P-450 by allylisopropylacetamide: impact on electron transfer. AB - Application of a single dose of allylisopropylacetamide (AIA) to phenobarbital pretreated rabbits resulted in partial destruction of the heme moiety of liver microsomal cytochrome P-450. A minor fraction of chromophore loss was accounted for by heme-derived product(s) covalently attached to microsomal proteins. Interestingly, cytochrome P-450 appeared to have undergone significant drug mediated alkylation of the apohemoprotein. The modified species was purified to apparent homogeneity and shown to arise from AIA-induced blockage of about 2 histidines in the cytochrome P-450LM2 molecule located close to the heme edge. AIA administration to the animals caused inhibition of hexobarbital-promoted electron flow from NADPH-cytochrome P-450 reductase to phenobarbital-inducible ferricytochrome P-450 both in microsomal particles and reconstituted systems. The impaired interaction between the proteins was shown not to originate from decreased capacity to bind each other but more likely to be due to some defect in a step subsequent to complex formation. In contrast, treatment with the porphyrogenic agent did not affect microsomal electron transmission from cytochrome b5 to the ferric monooxygenase. However, when the intermediate carrier was to donate reducing equivalents to the ferrous oxycytochrome in the presence of benzphetamine, there was a pronounced deceleration of the electron flux observable. These findings were interpreted to mean that there exist multiple reductase- and cytochrome-b5-binding domains in phenobarbital-inducible cytochrome P-450, some of which seem to be common to the two redox proteins. This sheds interesting light on the molecular organization of the catalytic electron transfer complexes. PMID- 8457585 TI - Inhibition of the plasma-membrane H(+)-ATPase from Dunaliella adidophila by omeprazole. AB - The acid-activated sulfhydryl reagent omeprazole inhibits light-induced H+ secretion at pH 1 in cells of the halotolerant alga Dunaliella acidophila. Plasma membrane vesicles, prepared from omeprazole-treated cells, have impaired vanadate sensitive ATPase and ATP-induced H+ uptake activities. Omeprazole inhibits ATPase activity also in isolated plasma-membrane vesicles. The inhibition is enhanced at acidic pH and can be prevented by protonophores indicating that it is promoted by internal acidification of the vesicles. Mercaptoethanol partially reverses omeprazole inhibition. ADP does not afford protection against omeprazole but it does protect against inhibition by N-ethylmaleimide, indicating that these reagents modify different sulfhydryl groups. It is suggested that omeprazole blocks SH groups of the D. acidophila plasma-membrane H(+)-ATPase, which face the outer side of the cell. PMID- 8457586 TI - Molecular modeling studies on the proposed NaCl-induced dimerization of Chromatium vinosum high-potential iron protein. AB - Previous work (Dunham, W.R., Hagen, W.R., Fee, J.A., Sands, R.H., Dunbar, J.B., Humblet, C. (1991) An investigation of Chromatium vinosum high-potential iron sulfur protein by EPR and Mossbauer spectroscopy; evidence for a freezing-induced dimerization in NaCl solutions, Biochimica Biophysica Acta 1079, 253-262) suggested that under specific solution conditions and slow freezing times, samples of oxidized Chromatium vinosum (Cv) high-potential, iron-sulfur protein (HiPIP) form dimeric structures that exhibit characteristic spin-spin interaction in the EPR spectrum. In that study, it was also shown that two HiPIP molecules could approach each other along their Fe1-S4 axes to a distance of approximately 13-14 A, as required by an analysis of the spin-spin physics. This is made possible because of a flattened surface on one side of the molecule within which S4 may, depending on side-chain motions, interact with solvent (Carter, C.W., Jr., Kraut, J., Freer, S.T., Alden, R.A., Sieker, L.C., Adman, E.T., Jensen, L.H. (1972) A comparison of Fe4S4 clusters in high potential iron protein and in ferredoxin, Proc. Natl. Acad. Sci. USA 69, 3527-3529). Here we describe a computer generated, hypothetical model of this proposed dimeric structure which suggests an energetically favorable interaction between two Cv HiPIP molecules and could account for the experimental observations. Two Cv HiPIP molecules brought together along their Fe1-S4 axes and maintained at a center-to-center distance of 14 A can be rotated with respect to each other so as to create complementary interactions between two glutamine residues, two phenylalanine residues, and two leucine residues, and an energetically unfavorable interaction between two arginine residues. Energy minimization calculations using the program XPLOR indicate that this arrangement may provide an overall energetically favorable interaction between the two HiPIP molecules that is strengthened by site-specific binding of Na and Cl ions. PMID- 8457587 TI - Role of oligomeric interactions in the cooperativity of crayfish hemocyanin. AB - To examine the effect of interactions between the hexameric units in the dodecameric hemocyanin, crayfish (Procambarus clarki) hemocyanin was partially dissociated. Gel-filtration yielded fractions containing the undissociated dodecamer and a mixture of the hexamer and heptamer (referred to as 'half dodecamer'). Their O2 equilibria were compared and were analyzed by curve fitting of cooperativity models. The partial dissociation of the dodecamer significantly lowered the cooperativity but little affected the O2 affinities. The O2 equilibrium of the half-dodecamer could be described by the two-state allosteric model of Monod-Wyman-Changeux on the assumption that the cooperative unit is composed of six subunits. We tested the applicability of allosteric models for the dodecamer that deal with the interactions between the hexamers. To reduce the arbitrariness of the fitting, we presumed that some parameters are equal to the two-state model parameters for the half-dodecamer. It was found that the 'nesting model', which assumes allosteric equilibria at two different hierarchical levels, could be applied successfully to the dodecamer. PMID- 8457588 TI - Mode of action of three endo-beta-1,4-xylanases of Streptomyces lividans. AB - The mode of action of three genetically distinct endo-beta-1,4-xylanases (EXs) of Streptomyces lividans, XlnA, XlnB and XlnC, belonging to two different xylanase families, was investigated on a variety of polysaccharide and oligosaccharide substrates. Viscosimetric measurements showed that all three enzymes have about the same endo-acting character. Occurrence of multiple pathways of substrate degradation at high concentration of beta-1,4-xylooligosaccharides suggested that all three enzymes were retaining glycanases. The enzymes differed considerably in their mode of action on various heteroxylans and on rhodymenan. XlnA hydrolyzed all tested polysaccharides to a higher degree than XlnB or XlnC, through liberation of smaller hydrolysis products, both linear or branched. XlnA performed much better than XlnB or XlnC, particularly on acetylxylan, liberating large amounts of short acetylated and non-acetylated fragments. XlnB and XlnC liberated from acetylxylan only limited amounts of larger acetylated fragments. XlnA exhibited also much higher catalytic efficiency than the other two EXs on short beta-1,4-xylooligosaccharides. The kinetic parameters and bond-cleavage frequencies determined for xylotriose, xylotetraose and xylopentaose using 1-3H reducing-end-labelled compounds suggested that the substrate binding site of XlnA is smaller and differently organized than those in XlnB or XlnC. In contrast to XlnB and XlnC, XlnA also exhibited significant aryl-beta-xylosidase activity. No distinctive catalytic properties of either XlnB or XlnC were found which were not inherent also to XlnA. High-molecular-mass EXs of the XlnA type show much greater catalytic versatility due than low-molecular-mass EXs of the XlnB or XlnC type. PMID- 8457589 TI - Expression of smooth muscle and nonmuscle tropomyosins in Escherichia coli and characterization of bacterially produced tropomyosins. AB - The cDNA encoding the beta-tropomyosin isoform of chicken smooth muscle (CSM beta) was constructed and expressed in Escherichia coli to produce recombinant, unacetylated beta-tropomyosin (rCSM beta) and a mutant (rCSM beta-7) with a 7 residue deletion at its amino-terminus. Furthermore, the cDNA coding for human fibroblast tropomyosin isoform 3 (hTM3) was also used to produce unacetylated hTM3 (called PEThTM3). All of bacterially-made tropomyosins were high alpha helical in structure as judged by CD analysis and resistant to heat denaturation. Both the rCSM beta and PEThTM3 exhibited saturable binding to F-actin with apparent binding constants of 1.14 x 10(6) and 2.78 x 10(6) M-1, respectively. The bacterially made, unacetylated smooth muscle tropomyosin (rCSM beta) appeared to have a comparable actin-binding affinity to that of gel-purified CSM beta homodimer (1.25 x 10(6) M-1) but significantly lower than that for native gizzard tropomyosin (CSM-TM) heterodimer (1.28 x 10(7) M-1). The amino-terminal deletion mutant rCSM beta-7 failed to bind to F-actin. Effects of gizzard caldesmon on the actin binding of these bacterially made tropomyosins were also examined. Under the binding condition containing 0.5 mM MgCl2 and 30 mM KCl, caldesmon greatly enhanced the binding of rCSM beta to F-actin. However, under the same condition, there was a slight enhancement in the actin-binding for gel-purified CSM beta or PEThTM3 (1.2-1.6-fold stimulation) and no enhancement for native gizzard tropomyosin. Neither the presence of caldesmon nor native gizzard tropomyosin induced detectable binding of the amino-terminal deletion mutant rCSM beta-7 to F actin. These results clearly imply the importance of the amino-terminal 7 amino acid residues of CSM beta in the actin binding and the caldesmon enhancement. PMID- 8457590 TI - Substrate specificity of 'elastomucoproteinase': an enzyme which can degrade cartilage aggrecan. AB - The substrate specificity of elastomucoproteinase (EMP), an enzyme which was first isolated from crude pancreatic elastase and described as a proteoglycan degrading enzyme, determined on tripeptide-p-nitroanilide substrates indicates the existence of a 'new' chymotrypsin-like enzyme. EMP, however, did not cleave any glycosaminoglycans, i.e., its 'mucolytic' effect has been excluded. Activity of EMP on synthetic or protein substrates (e.g., collagen type-II and aggrecan of cartilage) was completely inhibited by serine proteinase inhibitors, which was also found when using cartilage proteoglycan monomers. EMP cleaves the core protein of proteoglycan monomer (aggrecan) into small peptides, some containing glycosaminoglycan chains resulting in an unusual elution profile on Sepharose CL 6B chromatography when compared to the effects of pancreatic and granulocyte elastases, chymotrypsin, cathepsin G and stromelysin. EMP-like activity also was detected in neutrophil granules of bovine leukocytes and polyclonal antibodies were raised against purified bovine EMP to detect the enzyme in both crude elastase preparations and the granule fraction of bovine leukocytes. PMID- 8457591 TI - Activity modulation of the fast and slow isozymes of human cytosolic low molecular-weight acid phosphatase (ACP1) by purines. AB - The activity modulation of homogeneous isozymes of the human cytosolic M(r) 18,000 acid phosphatase (ACP1) by purines has been investigated. A pronounced difference in the response of fast and slow isozymes of the same genetic type was observed, while identical properties were found for fast isozymes encoded by different alleles (ACP1 X A, B and C), as well as for the corresponding slow isozymes. The catalytic rate constant (kc) of the fast isozymes was increased 5.1 fold by hypoxanthine and decreased 40% by adenine, while the kc of the slow isozymes was unaffected by hypoxanthine but increased 4.6-fold by adenine. This finding and the genetically-determined differences in the relative quantities of the fast and slow isozymes account for the well-known phenotypic differences in activity modulation. The kinetic results strongly indicate that the effector binds to the free enzyme, as well as to the enzyme-substrate complex. Activating effectors showed a higher affinity for the free enzyme than for the enzyme substrate complex, while the reverse was true with the inhibitor. The results exclude the possibility that effector and substrate bind to the same site of the enzyme; parasteric binding to adjacent sites is suggested. PMID- 8457592 TI - Differential regulation of S-adenosylmethionine synthetase isozymes by gibberellic acid in dwarf pea epicotyls. AB - Dwarf pea epicotyls contained a single activity peak of S-adenosylmethionine (AdoMet) synthetase (isozyme I). Gibberellic acid (GA3, 1 microM) induced two additional isozymes (II and III). Cycloheximide (20 microgram/ml) blocked the appearance of GA3-induced isozymes, suggesting that it is dependent on de novo protein synthesis. Conclusive proof was obtained by labelling the isozymes II and III with [35S]SO2-(4) in vivo. The purified 35S-labelled AdoMet synthetase isozymes (II, III) showed a single protein band that coincided with the single radioactive peak on SDS-PAGE. Molecular-sieve chromatography of the isozyme I from control dwarf pea epicotyls and three isozymes of GA3-treated epicotyls on Sepharose CL-6B showed a single activity peak with an identical molecular mass of 174 kDa for each isozyme. Analysis of purified AdoMet synthetase isozymes (I, II, III) on SDS-PAGE showed a single silver-stained protein band with a molecular mass of 87 kDa. This proved the dimeric nature of all the isozymes of AdoMet synthetase which could be physically separated by ion-exchange chromatography on DE-52. In vitro molecular hybridization of physically separated isozymes by NaCl freeze-thaw treatment method revealed that the three isozymes (I, II, III) in GA3 treated dwarf pea epicotyls are formed through the random dimerization of two different species of enzyme subunits that differ in their net charge. Thus, the two flanking activity peaks (isozymes I, III) represent homodimers, while the middle activity peak (isozyme II) is a heterodimer. Apparently, the single isozyme I in control epicotyls is a product of one gene of AdoMet synthetase (SAM 1), while three isozymes in GA3-treated epicotyls are the product of two genes of AdoMet synthetase. We speculate that the differential regulation of AdoMet synthetase in GA3-treated epicotyls is achieved by the expression of an alternate gene of AdoMet synthetase (SAM 2). PMID- 8457593 TI - A comparative study of the conformational properties of Escherichia coli-derived rat intestinal and liver fatty acid binding proteins. AB - Fourier transform infrared spectroscopy has been used to examine the conformation in aqueous solution of Escherichia coli-expressed rat intestinal and liver fatty acid binding proteins (I-FABP and L-FABP, respectively). While I-FABP is known from X-ray analysis to have a predominantly beta-structure with 10 antiparallel beta-strands forming two orthogonal sheets that surround the ligand binding pocket, no structural data are available for L-FABP. As expected for homologous proteins with related functions, the secondary structures of I-FABP and L-FABP are very similar. In both proteins, the conformation-sensitive amide-I band shows the maximum absorption at around 1630 cm-1, proving that beta-sheet is the major structural element. However, there are three critical differences between I-FABP and L-FABP; (i), a different solvent accessibility of the protein backbone; (ii), a different pH sensitivity and (iii), a different thermostability, with L-FABP being thermally more stable than I-FABP. These results suggest that, in spite of having a similar overall conformation, the architecture of these proteins is stabilized by slightly different interactions. Such dissimilarities, well paralleled by fatty-acid binding studies, may provide a structural basis for their functional diversification. PMID- 8457594 TI - Labeling of tyrosines in proteins with [15N]tetranitromethane, a new NMR reporter for nitrotyrosines. AB - Lysozyme and ribonuclease were used as model proteins to explore the feasibility of detecting protein-bound nitrotyrosines by 15N-NMR spectroscopy. The reporter group was introduced via synthesized [15N]tetranitromethane. Several experiments for detection of the 15N resonance in the model [3-15N]nitrotyrosine demonstrated a substantial pH-dependence of the chemical shift. When lysozyme was nitrated, either two or three 15N resonances were detected, depending on the extent of nitration. The pH-dependence of the detected resonances clearly described an apparent microscopic pK in accord with reported values, while addition of Gd(III) gave selective line broadening, indicating that the 15N reporter group could also monitor relative distances from paramagnetic sources. Nitration of ribonuclease showed five 15N resonances, of which three persisted in the purified monomer. The pH-dependence of these resonances also described apparent microscopic pK values. The [3-15N]nitrotyrosine model was reduced to the [3-15N]aminotyrosine and its 15N resonance was easily monitored by several methods, including selective population inversion. When the protein-bound nitrotyrosines were similarly reduced, much sample decomposition resulted, a possible result of photooxidation, and/or reduction of disulfide bond(s), thereby making interpretation difficult. PMID- 8457595 TI - Interaction of inositol hexakisphosphate with liganded ferrous human hemoglobin. Direct evidence for two functionally operative binding sites. AB - Inositol hexakisphosphate (InsP6) binding to the oxygenated, carbonylated and nitrosylated derivatives of ferrous human hemoglobin (HbO2, HbCO and HbNO, respectively) has been measured at pH 7.0 (0.1 M Bis-Tris buffer, 0.1 M NaCl) and 20 degrees C. The observations indicate the presence of two InsP6 binding sites per tetramer in all the heme liganded hemoglobin derivatives, with different affinities for the polyphosphate. For each binding site, InsP6 interacts with similar affinity constants to HbO2, HbCO and HbNO. Such a finding indicates that different heme ligands do not alter significantly the stereochemistry of the polyphosphate binding cleft. This behaviour seems to indicate that, even though different heme ligands are likely to affect the tertiary conformation of the subunit in a different fashion, the perturbation does not seem to be transmitted to the quaternary arrangement of the whole macromolecule, and, thus, to the InsP6 binding site. PMID- 8457596 TI - Nucleotide cofactor-binding-domain-specific antibodies show immunologic relatedness among unrelated proteins that bind phosphoryl compounds. AB - The immunologic relatedness of various cofactor-binding sites of enzymes requiring different nucleotide cofactors was examined. Chicken antibodies specific for NADPH- or CoA-binding domains were raised using an NADPH- or CoA requiring enzyme as an immunogen. Antibodies specific for either NADPH- or CoA binding domains were isolated by immunoaffinity chromatography of the respective antisera using unrelated NADPH- or CoA-requiring enzymes as affinity ligands. The reactivities of the NADPH- and CoA-binding-site-specific antibodies with a variety of enzymes that required different cofactors was shown on Western blots of SDS-PAGE of the enzymes. Variable cross-reactivities were observed among all nucleotide-cofactor requiring enzymes with each specific cofactor-domain-antibody population. Numerous proteins not physiologically associated with nucleotide cofactors, including acyl carrier protein, were completely unreactive. Proteins that bound phosphoryl compounds either as substrates or cofactors showed varying degrees of reactivity with each population of specific antibodies. These included aldolase, ribulose-1,5-bisphosphate carboxylase/oxygenase, ribonuclease A, carbonic anhydrase and triosephosphate isomerase. The immunologic cross reactivity suggested that these proteins share a common structural feature, probably a primary structure epitope, since the proteins had been subjected to denaturing polyacrylamide gel electrophoresis. A candidate for this common structural feature is a glycine-rich sequence comprising a phosphate binding loop. PMID- 8457597 TI - Some properties of restriction endonuclease ApaBI from Acetobacter pasteurianus. AB - A new site-specific endonuclease has been isolated from Acetobacter pasteurianus and has been named ApaBI. The enzyme recognizes 35 cleavage sites on bacteriophage lambda DNA, 20 sites on adenovirus-2 DNA and 2 sites on plasmid pBR322. The recognition sequence for this enzyme is 3'-CGT/NNNNNACG-5' 5' GCANNNNN/TGC-3'. PMID- 8457598 TI - Cooperativity in the antibody binding to surface-adsorbed antigen. AB - The binding to surface-adsorbed antigen of monoclonal mouse IgG-antibodies (mAbs), with two different affinities to dinitrophenyl (DNP), was measured by a calibrated ELISA. The concentration-dependence of antibody binding to surface bound antigen of different epitope densities was analysed using Scatchard plots. The dissociation of bound tritium-labelled antibodies was measured in the presence of unlabelled antibodies in the bulk. At low surface concentration of bound anti-DNP, both high-affinity mAb and low-affinity mAb show a positive cooperativity in the binding reaction to antigen of high epitope density. Using antigen of lower epitope densities, the positive cooperativity is more pronounced for low-affinity clones. At higher surface concentrations of bound anti-DNP, the Scatchard plots indicate a negative cooperativity of binding, which is also implied by the increased dissociation found in the presence of antibodies in solution. The study confirms previous findings that the binding of antibodies to surface-bound antigen not only depends on intrinsic antibody affinity measured in solution. Other factors, such as self-interaction, also affect the heterogeneous binding reaction. PMID- 8457599 TI - Subcellular fractionation of cultured normal human melanocytes: new insights into the relationship of melanosomes with lysosomes and peroxisomes. AB - In order to obtain information on the disputed nature of melanosomes a comparison was made between the localization of melanosomal markers with those of other well defined subcellular organelles such as lysosomes and peroxisomes. The distribution of marker enzymes was studied using two different density gradient systems, i.e., Percoll and Nycodenz. Furthermore, the subcellular localization of various types of antigens was analyzed using indirect immunofluorescence and immuno-electron microscopy. All methods revealed the existence of partial co localization of melanosomal and lysosomal proteins and different localization of peroxisomal markers. The results suggest that melanosomes may share a common origin with lysosomal structures. PMID- 8457600 TI - The effects of vitamin D deficiency on proteoglycan and hyaluronate constituents of chick bone. AB - The effect of vitamin D deficiency on proteoglycan and hyaluronate constituents of cortical diaphyseal chick bone was studied. Proteoglycans in rachitic bone showed no significant change with respect to their size, composition, or amount relative to other extractable macromolecular components. In contrast, bone hyaluronate levels were raised in chicks fed on diets that were either vitamin D deficient or depleted in calcium or phosphate, a 7-fold increase being seen in hypocalcaemic vitamin D-deficient chicks. This increase in hyaluronate was not directly related either to the absence of vitamin D or to abnormal levels of blood calcium or phosphate per se; hyaluronate levels are probably regulated by another factor, not yet identified, that is responsive to changes in vitamin D and mineral metabolism. PMID- 8457601 TI - Pleotrophic action of interferon gamma in human orbital fibroblasts. AB - Analysis of the two-dimensional electrophoretic patterns of total radiolabeled cellular proteins derived from human orbital fibroblast cultures revealed that interferon gamma (100 U/ml) elicited significant quantitative changes in 42% of 86 randomly-selected proteins relative to untreated cultures. The most substantial up-regulation involved a protein with pI/mw map coordinates of 5.9/54,000 and a heterogenous 5 isoform protein cluster (pIs = 6.1-5.6) of approximately 47- to 50-kDa. These proteins were identified as the previously described 54-kDa protein inducible in interferon gamma-sensitive cell types and type-1 plasminogen activator inhibitor (PAI-1), respectively. Definition of PAI-1 as an interferon gamma-responsive protein in orbital fibroblasts was confirmed by immunoprecipitation using PAI-1-specific antibodies. Induction of PAI-1 and the 54-kDa protein in orbital fibroblasts, moreover, was relatively specific for interferon gamma since interferon alpha failed to initiate a similar inductive response. The synthesis of a 170 kDa protein, tentatively identified as a collagen, was decreased by approximately 80%. Analysis of the labeled proteins secreted into the culture medium revealed that interferon gamma increased the medium content of fibronectin and decreased the secretion of collagen. It would appear from these data that the inflammatory cytokine can exert regulatory effects on the synthesis of many specific proteins in orbital fibroblasts. PMID- 8457602 TI - Interleukin-1 binding and prostaglandin E2 synthesis by amnion cells in culture: regulation by tumor necrosis factor-alpha, transforming growth factor-beta, and interleukin-1 receptor antagonist. AB - Proinflammatory cytokines may promote preterm labor in the setting of intrauterine infection. Tumor necrosis factor (TNF) and interleukin-1 (IL-1) synergistically stimulate the production of prostaglandin E2 (PGE2) by amnion cells. Transforming growth factor-beta (TGF-beta) inhibits the cytokine stimulated PGE2 production. In the present study, we investigated the binding of IL-1 beta on human amnion cells in culture. Untreated amnion cells possessed 540 +/- 60 IL-1 receptors per cell, with a dissociation constant of 1.4 +/- 0.4 nM. Cells treated with TGF-beta 1 (10 ng/ml) had 570 +/- 110 receptors per cell. TNF alpha (50 ng/ml) increased the number of IL-1 receptors to 2930 +/- 590. TGF-beta 1 inhibited the receptor upregulation by TNF-alpha. Cells treated with TGF-beta 1 and TNF-alpha expressed 1140 +/- 590 receptors per cell. The binding affinity was not changed by the cytokines. IL-1 receptor antagonist (IL-1ra) inhibited the stimulation of amnion cell PGE2 production by IL-1 beta, but not by TNF-alpha. Amnion cells secreted large amounts of IL-1ra (1.1 +/- 0.3 ng/10(5) cells). Treatment of the cells with TGF-beta 1 or TNF-alpha did not affect the release of IL-1ra. We conclude that IL-1 receptor expression is an important step in the regulation of the effects of cytokines on amnion cell PGE2 production. PMID- 8457603 TI - Characterization of Ca(2+)-dependent neutral protease (calpain) from human blood flukes, Schistosoma mansoni. AB - Calcium-dependent, neutral cysteine-proteases (calpain) were purified from human blood flukes, Schistosoma mansoni. The electrophoretic mobilities, Western blot analyses and high specificity to peptide inhibitors confirmed the presence of both calpain I and II in the purified preparation. The schistosome calpains were localized in the surface syncytial epithelium and underlying musculature. Using peptide inhibitors, calpain was shown to function as a mediator of the surface membrane synthetic process. Since there was also no immunological cross reactivity between vertebrate and schistosome calpains using antibodies affinity purified from native and recombinant schistosome calpains, this protease may be usefully investigated as forming the basis of a molecular vaccine against schistosomiasis. PMID- 8457604 TI - The effect of felodipine on the uptake and degradation of acetylated LDL in mouse peritoneal cells and on the distribution of acetylated LDL in macrophage-rich organs of the rat. AB - The effect of felodipine on lipoprotein metabolism ex vivo and in vivo was investigated. In the ex vivo studies mice were given felodipine (40-125 mumol/kg body weight) or vehicle for one week. Peritoneal macrophages from these animals and controls were isolated and used in binding and degradation studies with human iodinated acetylated LDL (Ac-LDL). Macrophages from felodipine-treated mice showed a significant decrease of binding and degradation of Ac-LDL compared to macrophages from control animals (P < 0.05). The in vivo studies were performed in rats pretreated with felodipine or vehicle. To determine the distribution and plasma turnover of LDL and Ac-LDL, 125I-tyramine cellobiose labelled LDL or Ac LDL were given i.v. No differences in the removal rate of Ac-LDL or LDL were observed between felodipine-treated or untreated rats. However, an increased uptake of Ac-LDL could be seen in the liver of the felodipine-treated rats. This increased uptake could be ascribed to the parenchymal cells because no differences in uptake could be seen in the liver endothelial cells. However, a significant decreased uptake was seen in the Kupffer cells and in the spleen, a macrophage-rich organ, of the felodipine-treated rats. The present study suggests a possible mechanism behind the antiatherogenic effects of calcium antagonists, a decreased uptake of atherogenic modified lipoproteins by peripheral macrophages and an increased uptake by the liver. PMID- 8457605 TI - Phagocytosis of P. falciparum malarial pigment hemozoin by human monocytes inactivates monocyte protein kinase C. AB - Hemozoin (malarial pigment) is a ferriprotoporphyrin IX-rich hemoglobin degradation product present in parasitized RBC. Avidly phagocytosed hemozoin abolishes phagocyte TPA-induced oxidative burst. Membrane-associated PKC increased transiently in hemozoin-fed monocytes by 50% after 30 min and decreased irreversibly to 20% of initial value within 5 h after phagocytosis. Control RBC fed monocytes showed transient decay of membrane-associated PKC followed by complete recovery 12 h after phagocytosis. Cytosolic PKC was not impaired within 12 h and diminished drastically 24 h after phagocytosis of hemozoin. Results are compatible with increased degradation of membrane-translocated PKC, possibly by iron/H2O2-mediated damage of cysteine-rich regulatory domains of PKC. PMID- 8457606 TI - Demonstration of the existence of a second, non-lysosomal glucocerebrosidase that is not deficient in Gaucher disease. AB - In addition to the lysosomal glucocerebrosidase, a distinct beta-glucosidase that is also active towards glucosylceramide could be demonstrated in various human tissues and cell types. Subcellular fractionation analysis revealed that the hitherto undescribed glucocerebrosidase is not located in lysosomes but in compartments with a considerably lower density. The non-lysosomal glucocerebrosidase differed in several respects from lysosomal glucocerebrosidase. The non-lysosomal isoenzyme proved to be tightly membrane bound, whereas lysosomal glucocerebrosidase is weakly membrane-associated. The pH optimum of the non-lysosomal isoenzyme is less acidic than that of lysosomal glucocerebrosidase. Non-lysosomal glucocerebrosidase, in contrast to the lysosomal isoenzyme, was not inhibited by low concentrations of conduritol B epoxide, was markedly inhibited by taurocholate, was not stimulated in activity by the lysosomal activator protein saposin C, and was not deficient in patients with Gaucher disease. Non-lysosomal glucocerebrosidase proved to be less sensitive to inhibition by castanospermine or deoxynojirimycin but more sensitive to inhibition by D-gluconolactone than the lysosomal glucocerebrosidase. The physiological function of this second, non-lysosomal, glucocerebrosidase is as yet unknown. PMID- 8457607 TI - S-adenosylmethionine synthetase in bloodstream Trypanosoma brucei. AB - S-adenosylmethionine synthetase was studied from bloodstream forms of Trypanosoma brucei brucei, the agent of African sleeping sickness. Two isoforms of the enzyme were evident from Eadie Hofstee and Hanes-Woolf plots of varying ATP or methionine concentrations. In the range 10-250 microM the Km for methionine was 20 microM, and this changed to 200 microM for the range 0.5-5.0 mM. In the range 10-250 microM the Km for ATP was 53 microM, and this changed to 1.75 mM for the range 0.5-5.0 mM. The trypanosome enzyme had a molecular weight of 145 kDa determined by agarose gel filtration. Methionine analogs including selenomethionine, L-2-amino-4-methoxy-cis but-3-enoic acid and ethionine acted as competitive inhibitors of methionine and as weak substrates when tested in the absence of methionine with [14C]ATP. The enzyme was not inducible in procyclic trypomastigotes in vitro, and the enzyme half-life was > 6 h. T. b. brucei AdoMet synthetase was inhibited by AdoMet (Ki 240 microM). The relative insensitivity of the trypanosome enzyme to control by product inhibition indicates it is markedly different from mammalian isoforms of the enzyme which are highly sensitive to AdoMet. Since trypanosomes treated with the ornithine decarboxylase antagonist DL alpha-difluoromethylornithine accumulate AdoMet and dcAdoMet (final concentration approximately 5 mM), this enzyme may be the critical drug target linking inhibition of polyamine synthesis to disruption of AdoMet metabolism. PMID- 8457608 TI - Response of normal and reperfused livers to glucagon stimulation: NMR detection of blood flow and high-energy phosphates. AB - The effects of glucagon on blood flow and high-energy phosphates in control and in rat livers damaged by ischemia were studied using in vivo nuclear magnetic resonance (NMR) spectroscopy. Normal livers and livers which had been made ischemic for 20, 40, and 60 min followed by 60 min of reperfusion were studied. Ischemia led to a loss in adenosine triphosphate (ATP) within 30 min. Reperfusion after 20 min of ischemia led to complete recovery of ATP. 60 min of reperfusion after 40 or 60 min of ischemia led to only a 76% and 48% recovery of ATP, respectively. Glucagon, at doses up to 2.5 mg/kg body weight, caused no changes in the inorganic phosphate (P(i)) to ATP ratio in normal livers as measured by 31P-NMR spectroscopy. In livers which had been made ischemic for 20, 40, or 60 min, glucagon caused an increase in the P(i)/ATP ratio of 18%, 40%, and 40%, respectively. 19F-NMR detection of the washout of trifluoromethane from liver was used to measure blood flow. Glucagon-stimulated flow in the normal liver in a dose-dependent manner, with 2.5 mg glucagon/kg body weight leading to a 95% increase in flow. Ischemia for 20, 40, and 60 min followed by 60 min of reperfusion led to hepatic blood flows which were 63%, 68%, and 58% lower than control liver. In reperfused livers, blood flow after glucagon-stimulation was reduced to 56%, 43%, and 48% of control glucagon-stimulated flow after 20, 40, and 60 min of ischemia. These results indicate that ischemia followed by reperfusion leads to decreases in hepatic blood flow prior to alterations in ATP and the response of the liver to glucagon is altered in the reperfused liver. PMID- 8457609 TI - PCR amplification using a single cell allows the detection of the mtDNA lesion associated with Leber's hereditary optic neuropathy. AB - The development of the polymerase chain reaction (PCR), which routinely can amplify specific target sequences more than one billion-fold, has made it possible to produce readily detectable amounts of DNA from a few copies of very rare sequences. We have begun a study of mitochondrial myopathies with the purpose of developing a diagnostic test using PCR to amplify appropriate mitochondrial DNA (mtDNA) target sequences from small amounts of sample. We have developed a 15-min procedure for recovering mtDNA which can be amplified by PCR to detectable levels, from as little as 30 microliters of blood or 5 microliters of amniotic fluid. We have microscopically selected HL60 cells, and have found that 28 cycles of PCR allows the detection of mitochondrial targets from a single cell. Using micromanipulation techniques, we utilized this approach to analyze mtDNA from a single cell isolated from an 8-cell stage mouse blastocyst. Finally, a single cell cultured from a patient with Leber's hereditary optic neuropathy, a mitochondrial myopathy, provided sufficient mtDNA for detection of the single base substitution that leads to loss of a restriction endonuclease recognition site for SfaNI and generation of a site for MaeIII. PMID- 8457610 TI - Structural organisation of band 3 in Melanesian ovalocytes. AB - The diffusional freedom of human erythrocyte band 3 (anion exchanger 1) has been measured in membranes from normocytic and ovalocytic erythrocytes. A dramatic reorganisation of band 3 in the ovalocyte membranes is indicated by a markedly restricted rotational mobility. Extraction of spectrin from erythrocyte membranes had no effect on normocyte band 3 mobility, but partially relieved the restrictions on ovalocyte band 3 mobility. Further removal of ankyrin and band 4.2 resulted in an increase in the rotational mobility of both ovalocyte and normocyte band 3 to similar levels. The results suggest that the molecular basis of the unusual shape and decreased deformability of ovalocytes resides in an altered interaction of band 3 with one or more of the peripheral proteins. We present a model which illustrates a possible role for band 3 aggregation in controlling erythrocyte deformability. PMID- 8457611 TI - Allogeneic bone marrow transplantation in acute myeloid and lymphocytic leukemia. AB - Allogeneic bone marrow transplantation is an accepted therapy for acute leukemia, with an increased rate of long-term survival and possible cure. Unfortunately, it can be given only when an HLA-identical donor is found. For this reason, large international registries containing normal HLA-typed volunteer marrow donors have been established. Although preliminary, results are encouraging. Approaches using stem cell purification and expansion, fetal and neonatal cells, and new immunosuppressive agents are currently under investigation. PMID- 8457612 TI - Therapy for chronic myelogenous leukemia with marrow transplantation. AB - Chronic myelogenous leukemia is a lethal disease of the hematopoietic stem cell. Marrow transplant from an HLA-matched sibling donor can cure some patients with chronic myelogenous leukemia. Best results are observed when patients receive transplants early in chronic phase. The advantages of delaying marrow transplantation for a trial of interferon-alpha are questionable if a suitable matched related donor is available. The high incidence of relapse following T lymphocyte-depleted marrow transplantation for chronic myelogenous leukemia emphasizes the existence of dormant, malignant clones that persist after ablative therapy. The presence of very small numbers of bcr-abl-positive hematopoietic cells after marrow transplantation can be detected by sensitive molecular genetic techniques and does not always predict hematologic relapse. Successful treatment of hematologic relapse after marrow transplantation can result from treatment with interferon-alpha, donor buffy coat cells, or second transplantation. HLA phenotypically matched and, in some cases, class I HLA antigen mismatched unrelated donors can be used successfully for marrow transplantation. Complications include an increased incidence of graft failure and graft-versus host disease. Younger patients undergoing transplantation early in the disease course fare best. Preliminary results suggest that autologous marrow transplantation can induce complete hematologic and cytogenetic remission and may prolong survival in some cases. Strategies are being developed to obtain benign primitive progenitors suitable for autologous marrow transplantation by positive selection and to develop further posttransplantation antileukemic cell therapy to be used as an adjunct to autologous marrow transplantation for chronic myelogenous leukemia. PMID- 8457613 TI - Autologous bone marrow transplantation. AB - Very high-dose cytotoxic therapy requiring bone marrow transplantation is the most active treatment for most hematologic malignancies and appears to be the treatment of choice for most patients with these diseases at relapse. Autologous bone marrow transplantation and allogeneic bone marrow transplantation can generally be expected to yield similar results in patients with lymphoma or acute leukemia; autologous bone marrow transplantation offers the advantage of greater availability and less toxicity but with a higher rate of tumor recurrence. Novel approaches that can increase the antitumor activity of autologous bone marrow transplantation without increasing the toxicity are being investigated. Dose intensification followed by autologous marrow rescue is also very active against responsive solid tumors, eg, breast cancer, ovarian cancer, testicular cancer, and pediatric solid tumors. However, it is difficult to demonstrate that autologous bone marrow transplantation has yet to lead to an improvement in disease-free survival for patients with solid tumors. Therefore, the exact role autologous bone marrow transplantation should play in the treatment of solid tumors remains to be established. PMID- 8457614 TI - Acute and chronic graft-versus-host disease. AB - Acute graft-versus-host disease is a two-step process. First, allorecognition of histocompatibility antigen activates T lymphocytes, which releases several cytokines, including interleukin-1 and tumor necrosis factor. Understanding of this activity resulted in new therapeutic approaches. Chronic graft-versus-host disease remains a very frequent and difficult problem to treat. Thalidomide was introduced as therapy for chronic graft-versus-host disease. Although basic research reported this year had no common theme, progress was made in many areas. PMID- 8457615 TI - Recent developments in experimental bone marrow transplantation. AB - Animal models have been a mainstay for the preclinical evaluation of the principles of bone marrow transplantation. In addition to evaluation of the therapeutic effectiveness of bone marrow transplantation in oncologic, hematologic, immunologic, and genetic diseases, experimental animal models provide insights into the immunobiology of bone marrow transplantation, including engraftment kinetics, tolerance, immune reconstitution, and graft-versus-host and graft-versus-tumor reactions. Many recent developments in experimental bone marrow transplantation resulted from not only the discovery of new spontaneously occurring models of human diseases but also the induction of neoplastic diseases, eg, chronic myelogenous leukemia, by transplantation of syngeneic marrow cells into which foreign genes were introduced and expressed. Murine bone marrow transplantation systems are an exemplary format for the study of clinically relevant basic aspects of hematopoiesis, including identification and elucidation of the biology of hematopoietic stem cells. Finally, the application of molecular biologic techniques in animal bone marrow transplantation models provides the preclinical foundations of gene-insertion therapy by transplantation of syngeneic or autologous marrow-derived stem cells into which functional genes were inserted. PMID- 8457616 TI - Biology of lung cancer. AB - New treatments of lung cancer are likely to develop from a greater understanding of the biology of lung tumors and the mechanisms of carcinogenesis and tumor progression. It is clear that numerous molecular genetic changes are present in lung cancer. Some of these changes, eg, mutated oncogenes, are found in other tumors. They provide clues about the carcinogenesis and pathogenesis of lung cancer. The relationship between these genetic changes and prognosis is becoming clearer. Study of membrane receptors for growth signaling and interaction of cells with their environment has identified factors relevant to prognosis and possible targets for therapy. Model systems to interfere with growth signaling have been developed. PMID- 8457617 TI - Epidemiology, prognostic factors, and prevention of lung cancer. AB - Lung cancer continues to be a leading cause of preventable death, with an estimated 123,000 of the 143,000 lung cancer deaths in the United States in 1991 directly attributable to tobacco smoking. Given that mortality from this disease has not changed appreciably in the past two decades and despite continuing advances in cancer treatment, a new emphasis is being placed on prevention and early detection research through the identification of high-risk individuals and the definition of useful biomarkers. This review summarizes the status of these efforts over the past year. PMID- 8457618 TI - Paraneoplastic syndromes associated with lung cancer. AB - Paraneoplastic syndromes are caused by systemic factors that are produced at a site distant from the primary tumor or its metastases. Although these syndromes can be observed in a variety of tumor types, they are commonly found in lung cancer, particularly small cell lung cancer. In this review, we focus on recent advances in the diagnosis and treatment of two of the more well-documented paraneoplastic syndromes--endocrinologic and neurologic systemic manifestations of cancer. PMID- 8457619 TI - Etiology, epidemiology, risk factors, and public health issues of melanoma. AB - Evidence for an increase in the incidence of melanoma and nonmelanoma skin cancers continues to accumulate. Survival after early melanoma is greater than 90%. Survival decreases as tumor thickness increases in a relationship that appears to be more smooth than stepwise. Further evidence that early intermittent sun exposure is a major determinant of risk for melanoma was derived from a case control study in a low-risk population and in a study on migrants to Australia. There is also additional evidence that clinically atypical nevi (dysplastic nevi) are strong predictors of melanoma risk. For public health efforts to be effective in reducing the mortality and morbidity from melanoma and nonmelanoma skin cancers, it is essential to understand the responses of the public and the professional to skin cancer detection efforts and educational programs. Results from several such programs are reviewed. An understanding of the genetics of melanoma continues to grow yet remains complex. PMID- 8457620 TI - Pathology and prognostic factors. AB - Cutaneous malignant melanoma and its precursors were the general subjects of the National Institutes of Health Consensus Conference held in January 1992. Particular emphasis was placed on the diagnosis of early melanoma, especially melanoma in situ, and the controversies surrounding dysplastic nevi. Recent studies of unusual nevi often confused with melanoma, eg, deep-penetrating (plexiform) nevus, combined nevus, desmoplastic melanocytic nevus, and Spitz nevus in childhood, provided detailed histologic criteria for their discrimination from melanoma. Rare or unusual forms of melanoma, including desmoplastic melanoma, neurotropic melanoma, a newly described variant angiotrophic melanoma, subungual melanoma, and balloon cell melanoma have been the subject of comprehensive histologic studies. Other histopathologic investigations have described the prevalence of histologic regression and intraepidermal pagetoid spread in melanomas and the histologic features of reexcision specimens of melanoma. New evidence suggests that the predominant cell type infiltrating melanoma is the monocyte-macrophage, and the expression of monocyte chemotactic protein-1 by melanoma may explain the recruitment of this cell type. Immunopathologic studies of melanocytic lesions were performed with various melanocyte-associated antigens (eg, HMB-45), proliferation antigens (eg, Ki-67), and progression markers (eg, epidermal growth factor receptor and HLA DR). HMB-45 binding has been localized ultrastructurally to early melanosome formation. Various prognostic factors, including gender, high-risk anatomic sites (particularly the scalp), race (black vs white patients), microscopic satellites, tumor volume, indices of proliferation and tumor cell motility, volume-weighted mean nuclear volume, DNA ploidy, and nucleolar organizer regions have been the subject of recent investigations. Analysis of many patients with long-term follow up has facilitated better prognostic modeling of melanoma. PMID- 8457621 TI - Management of precursors and primary lesions of melanoma. AB - A better understanding of the natural history of pigmented lesions has recently led to a more conservative surgical approach to the management of certain congenital, dysplastic, and other acquired melanocytic nevi. The treatment of primary melanoma is still based almost exclusively on the thickness of the primary lesion. Recent data showed that a surgical margin of 1 cm is appropriate treatment of most thin melanomas (1 mm or less in Breslow thickness), whereas thicker lesions may be removed with a surgical margin of 2 to 3 cm without adversely affecting the rate of local recurrence or patient survival. These recommendations are guidelines only and may be modified by the anatomic site and histologic subtype of tumor. The value of prophylactic lymph node dissection in the management of primary melanoma is still debated and awaits the results of randomized, prospective studies. PMID- 8457622 TI - Immunologic recognition of malignant melanoma by autologous T lymphocytes. AB - T lymphocytes specifically recognizing autologous tumor cells in vitro can be generated from melanoma patients. Recognition of tumor cells by both CD4 and CD8 lymphocytes is mediated through the T-cell receptor and is restricted by HLA antigens. Although HLA-A2 has been identified as a restricting allele for many melanoma-specific cytotoxic T lymphocytes, T cells directed against antigens unique to each patient's tumor as well as antigens common to melanomas from unrelated individuals can be restricted by several different HLA alleles. A common melanoma antigen recognized in association with HLA-A1 has now been identified. The antigen is a nonapeptide derived from the gene MAGE1, a normal cellular gene preferentially expressed in a variety of solid tumors. Melanoma cells have been found to produce a soluble form of the intracellular adhesion molecule-1. Soluble intercellular adhesion molecule-1 effectively inhibits cell mediated cytotoxicity in vitro, raising the possibility that its expression in vivo could promote escape of the tumor cells from immune effectors. PMID- 8457623 TI - Disseminated melanoma, preclinical therapeutic studies, clinical trials, and patient treatment. AB - Disseminated malignant melanoma is a very resistant tumor to therapy. Mechanisms of resistance to chemotherapy may be due to glutathione reductase and O6 alkyltransferase, two enzymes especially able to detoxify from alkylation. An interesting model is represented by dacarbazine in the treatment of melanoma with nitrosourea derivatives. Cytokines may come to play an increasing role in the combination with chemotherapy; interferon-alpha and interleukin-2, for example, seem to potentiate the action of chemotherapy in well-designed clinical protocols. Moreover, tumor necrosis factor-alpha was shown to be active in combination therapy with interferon-gamma and chemotherapy when administered by isolation perfusion. Targeting with monoclonal antibodies or melanocyte stimulating hormone-alpha conjugated to cytotoxic agents represents a promising area. The discovery of a gene, designated MAGE1, coding for a peptide presented by HLA-A1 and able to specifically activate cytotoxic T lymphocytes may represent a unique approach to specific active immunotherapy for melanoma. The interference with integrins and adhesion molecules may play a role in the prevention of metastases. Some preclinical models seem to validate this approach. Current treatment of disseminated malignant melanoma involves chemotherapy often associated with other cytotoxic agents or cytokines, which may potentiate the antitumor effect. Other therapeutic issues reviewed concern targeting and immunotherapy. This review ends with a survey of biologic factors that may constitute new approaches to melanoma therapy. PMID- 8457625 TI - Lung and mediastinum. PMID- 8457624 TI - Transplantation. PMID- 8457626 TI - Melanoma and other skin neoplasms. PMID- 8457627 TI - A tumor-elaborated supernatant factor chemotactic for IL-2 expanded tumor infiltrating T-lymphocytes. AB - Very little is known about factors influencing the migration of highly activated T-lymphocytes. One such lymphocyte population is the IL-2 expanded population of T cells infiltrating tumors. These tumor-infiltrating lymphocytes (TIL) can cause tumor regression in patients with metastatic cancer and in murine tumor models when given in adoptive transfer. In patients with melanoma, these TIL have been shown to migrate to sites of tumor and this may be a critical factor in their antitumor activity. In this study, a 48-well microchemotaxis chamber and a 5 microns pore nitrocellulose filter membrane system was utilized to study the motility of murine TIL. A chemotactic response was observed to supernatants from freshly explanted, autologous, and nonautologous tumor cultured for 24 h. Serially passaged autologous and nonautologous tumors also produced supernatants with chemotactic activity. Supernatants from single cell suspensions of normal tissues prepared and cultured identically did not elicit chemotaxis. Chemotactic activity for TIL was not removed by dialysis (2000 MW exclusion limit), its activity was undiminished by heat treatment at 60 degrees C for up to 60 min, and it was trypsin sensitive. Tumor supernatants were also chemotactic for two IL-2 dependent specifically alloreactive CTL lines (CTL-TIM and OE-4), but not two helper T cell lines (D-10 and D-1.5) or normal resting lymphocytes. This is the first demonstration of a chemotactic effect on IL-2-dependent, activated T cells. Characterization and purification of factors from tumor responsible for this directed migration are in progress. PMID- 8457628 TI - Presence of interferon-gamma and interleukin-6 in colostrum of normal women. AB - Colostrum and blood samples were obtained on postpartum day 2 and 3 from 17 lactating, healthy women. After delipidation and molecular sieving fractionation of colostrum, interferon-gamma (IFN-gamma) and interleukin-6 (IL-6) could be readily measured by using a sensitive immunoassay. Antiviral activity could be also measured in some colostrum samples suggesting that interferon was biologically active. On the contrary, corresponding plasma samples showed negligible activity. These results expand previous data showing the presence of IL-1, tumor necrosis factor (TNF-alpha), and IL-6 in normal colostrum and are in line with the concept of a basal cytokine production in physiological conditions. All of these cytokines probably act on the oropharyngeal and gut-associated lymphoid tissue of the newborn and favor the development and maturation of the immune system. PMID- 8457629 TI - Regulation of interleukin-2 and interleukin-4 receptor expression in human and ape lymphoid cell lines. AB - In this study, we have analyzed the expression and regulation of receptors for IL 2 (alpha and beta chains) and IL-4 in four lymphoid cell lines established from leukemic cells. The gibbon ape cell line MLA 144 was the only one to express constitutively the IL-2R beta chain and IL-4R, whereas the NK-like YT cells express only IL-2R beta. The two other cell lines in this study, PEER and HSB2, are derived from T lymphocytes, and express neither IL-4R, IL-2R beta, nor IL-2R alpha unless stimulated. We report here that those receptors that are constitutively expressed, i.e., IL-2R beta on YT cells and IL-2R beta or IL-4R on MLA cells, are down-regulated by stimulation with PHA + PMA. In contrast, RNase protection experiments showed that PHA + PMA stimulation of T cell lines induces mRNA for all three receptors in PEER cells, and only IL-2R alpha and IL-4R in HSB 2. Thus each of these three receptors is subjected to a different regulation, which in addition varies depending on the lineage (or differentiation stage) of the cells. This was further supported by the finding that IL-1 alpha or TNF-alpha regulates these receptors differently. These two cytokines have no effect on IL 2R beta and IL-4R in MLA and YT, but induce IL-2R alpha in YT. In contrast, they do not induce either chains of the IL-2R in the T cell lines PEER or HSB-2, but TNF induces IL-4R mRNA in HSB2 cells, and IL-1 does so in both cell lines.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457630 TI - Interleukin-4 production by the malignant cell line HUT78. AB - Interleukin-4 (IL-4) is a cytokine difficult to induce in large quantities in freshly isolated cells. No malignant cell line has been described to date to produce IL-4 either constitutively or following activation. Here we report that HUT78 cells can be induced to produce IL-4 either by CD3 stimulation under cross linking conditions or by soluble CD3 mAbs in the presence of PMA. IL-4-specific mRNA could be demonstrated readily under such conditions. Using this experimental model we investigated the role of IL-2 for IL-4 production. The addition of IL-2 strongly costimulated CD3-induced IL-4 production, whereas blockade of the IL 2/IL-2R pathway reduced IL-4 production by approximately 50%. IL-2 alone, however, could not induce IL-4 production. These results indicate that IL-2 is a helper of cytokine necessary, but not sufficient, for IL-4 production in HUT78 cells. PMID- 8457631 TI - Suppression of interleukin-6 production in endotoxin tolerance in a mouse glioma cell line: reversal by phorbol ester. AB - Tolerance to endotoxin (lipopolysaccharide, LPS) was shown to be mediated by an inhibition of cytokine production. We have studied the effect of 3-day pretreatment with LPS on production of IL-6 in response to a subsequent challenge with LPS in a mouse glioma. The results indicated that in this model, a complete blockage of IL-6 production is induced by LPS pretreatment. This is associated with a decrease of LPS-induced IL-6 mRNA levels. LPS-induced IL-6 production can be restored by PMA, as it was previously observed in vivo, suggesting that down regulation of IL-6 response in LPS tolerance occurs at the transcriptional level, probably by down-regulating protein kinase C or some other PMA-activable signaling system. IL-6 production is also down-regulated by 3-day preincubation with IL-6 and, to a lesser extent, with IL-1 or TNF, indicating that IL-6 can down-regulate its own production. PMID- 8457632 TI - Production and release of IL-1 beta by human peripheral blood monocytes in response to diverse stimuli: possible role of "microdamage" to account for unregulated release. AB - Three different stimuli [lipopolysaccharide (LPS), concanavalin A (Con A), and phorbol myristate acetate (PMA)] all induced production and release of interleukin-1 beta (IL-1 beta) from human monocytes in vitro. Of the three, LPS demonstrated the greatest potency for IL-1 beta production. LPS and Con A demonstrated similar efficacy with respect to IL-1 beta release. LPS was approximately 1000 times more potent than Con A in this regard. LPS- and Con A induced IL-1 beta release occurred within 3 h and 12-24 h, respectively. Challenge with PMA induced low levels of IL-1 beta production with a relatively large percentage released. IL-1 beta release by all three stimuli occurred at concentrations greater than or equal to those required for optimal IL-1 beta production. The amount of IL-1 beta released correlated with total IL-1 beta produced and was associated with release of lactate dehydrogenase (LDH), a cytosolic enzyme marker used to evaluate cell membrane integrity. IL-1 beta release preceded LDH release temporally. LPS and Con A had no effect on total cell protein synthesis, a measure of overt toxicity, while PMA inhibited protein synthesis in a dose-dependent fashion. LPS and Con A both induced expression of a 33- and 29-kDa precursor IL-1 beta, but only the 17-kDa form was released. These data suggest that IL-1 beta is released by a process different from regulated secretion. While PMA induces a more profound damage, LPS and Con A may stimulate release of IL-1 beta from human monocytes in vitro through induction of microdamage to the cell membrane. PMID- 8457633 TI - Induction of chromosomal rearrangement by tumor necrosis factors produced by primary B lymphoblastoid cells derived from cancer patients. AB - We have previously reported the isolation of the cytotoxic factors, tumor necrosis factor-alpha (TNF-alpha), from monocytes and lymphotoxin or TNF-beta, from an established human B lymphoblastoid cell line. In the current study, we examined the production of cytotoxic factors by primary lymphoid cells derived from patients with different malignancies and correlated it with the chromosomal abnormalities in producer cells. Lymphoid cell lines were established from 78 untreated patients with breast carcinoma, 2 with cervical carcinoma, 24 with colon carcinoma, 12 with prostate carcinoma, 3 with melanoma, and the remaining from asymptomatic family members. Lymphoid cells from all 119 patients and their asymptomatic family members constitutively produced as much as 240 units/ml of TNF-beta in vitro. In contrast, TNF-alpha was produced by lymphoid cells from only 6 patients; a related cytokine with similar biological properties to TNF beta. Sixty-five of these 119 samples were also analyzed for chromosomal abnormalities by standard cytogenetic technique. The production of TNFs was accompanied with varying degrees of chromosomal abnormalities in the cells from all patients. These included both structural and numerical abnormalities. We also examined the direct effect of TNF-beta on the induction of chromosomal abnormalities in growing cultures of both T and B lymphocytes. Our preliminary results indicate that treatment of lymphocytes with this cytokine induced chromosomal rearrangements in a dose-dependent manner. Thus, we provide for the first time both indirect and direct evidence that a soluble mediator such as TNF beta can induce chromosomal alterations commonly associated with different types of tumors. PMID- 8457634 TI - Growth in pinnipeds. AB - This review presents summary figures of, and fits growth curves to, data on body lengths (as standard length, SL, whenever possible) of pinnipeds at ages estimated to O.I y. (1) Generalized von Bertalanffy (vB) growth curves are fitted to most data: Lx = L infinity (I - ea(x-x0)b, Lx is length at age x, x0 is the origin of the curve (here chosen a priori as time of initiation of embryonic growth), L infinity is asymptotic length, a (which is negative) determines rate of approach to the asymptote, and b influences the 'shape' of the approach. (2) No single monotonic growth equation suffices for growth in length, which is linear before birth and remains so during early life. The vB equation is only suitable to describe mean lengths of newborns, and animals one or more years old. (3) Also, for males of polygynous species, two functions are needed to account for accelerated growth at puberty. Generally a Gompertz equation is adequate for adult males of these species. (4) The fitted growth equations permit statistical comparisons of sizes and growth rates, as well as of individual variability (as growth-curve residuals), among populations and species. (5) For the following species (including different populations when available), the reliability of data is assessed and parameters of growth curves are presented (with sexes separated where significantly different): walrus, California and Steller sea lions, Antarctic, subantarctic and northern fur seals, Hawaiian monk seal, crabeater, Weddell and Leopard seals, southern and northern elephant seals, bearded, hooded, ringed, Baikal, Caspian, spotted, harbour, harp, ribbon and grey seals. (6) Some novel findings pertain to individual species as follows. Although the Pacific walrus is generally stated to be the larger subspecies, females from Hudson Bay and males from Foxe Basin, in the eastern Canadian Arctic, may be as long as those from the Bering Sea. Although female Weddell seals have been assumed to grow larger than males, there is no significant difference in growth curves fitted to the most complete data. Uniquely among populations examined, the relative variability (absolute growth curve residuals/predicted lengths) of male southern elephant seals is amplified with age. Among ringed seals from Svalbard, the eastern, western and high Canadian Arctic, and the Bering, Chukchi, Okhotsk, Barents and Baltic Seas, asymptotic sizes are larger among those that breed on land-fast ice rather than floes, and size may be more variable in more extreme Arctic environments. The Baikal seal is confirmed as the smallest species of pinniped.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8457635 TI - Sensitive detection of the activation state of blood coagulation in porcine DIC models by a new fibrin immunoassay. AB - Elevated levels of soluble fibrin in plasma indicate that thrombin converts fibrinogen to fibrin without sufficient inhibitory control. Therefore, measurement of soluble fibrin (SF) in plasma may be considered as a laboratory test for intravascular coagulation. We have demonstrated that a new immunoassay for detection of SF in human plasma (Lill et al., Blood Coag Fibrinol 1993; 4: 97 102), based on a fibrin specific monoclonal antibody, also detects porcine SF with high sensitivity. Thrombin-dependent generation of SF in porcine plasma in vitro resulted in increased reactivity of the assay system, which was time and dose dependent. Dextran sulphate (DXS) and bacterial lipopolysaccharide (LPS) were used as stimuli in in vivo experiments in pigs. Plasma levels of SF increased steadily after intravenous administration of DXS (5 mg/kg for 1 h) to 38 +/- 7.8 micrograms/ml (mean +/- SEM) at 2 h, whereas LPS (2 micrograms/kg/h for 6 h) markedly increased plasma SF levels to over 120 micrograms/ml (at 6 h) after a lag phase of 2 h. In conclusion, this new immunoassay for human fibrin allows specific and sensitive detection of soluble fibrin in porcine plasma. PMID- 8457636 TI - The cleavage sequence of fibrinopeptide A from fibrinogen fragment E by thrombin, atroxin or batroxobin. AB - Calculations of data from fibrin polymerization and cross-linking experiments infer that thrombin-catalysed release of the second of the two fibrinopeptides A (FpA2) from fibrinogen is concerted, although other data suggest that FpA2 release is random. In the concerted pattern of FpA release, divalent monomer (des AA-fibrin) formation predominates throughout the enzymatic conversion of fibrinogen to fibrin, an effect leading to relatively rapid fibril assembly. Alternatively, random FpA2 release would result in a substantial population of monovalent monomer (des A-fibrin) intermediates during early and intermediate phases of the enzymatic conversion to fibrin. Their formation would cause a delay in fibrin fibril assembly. In order to address the question of the pattern of FpA release directly, we purified plasmic fibrinogen fragment E1 isoforms containing both FpA sequences and studied the sequence of FpA release by thrombin or batroxobin. Des A-fragment E1 intermediates formed by loss of one FpA (FpA1), and des AA-fragment E1 products (lacking both FpA1 and FpA2) were identified by analytical isoelectric focusing and quantified by densitometry. The catalytic rate of release of FpA1 (k1) and FpA2 (k2) by thrombin or batroxobin was similar. The ratio of these rates, k2:k1, was 1.10 +/- 0.42 for thrombin and 1.34 +/- 0.26 for batroxobin. These findings indicate that these enzymes cleave FpA2 randomly from fragment E1. PMID- 8457637 TI - Fibrin degradation products in growth stimulatory extracts of pathological lesions. AB - We have previously shown that similar patterns of fibrin degradation products (FbDP) by gel electrophoresis and immunoblotting are present in extracts of human atherosclerotic plaques, human and experimental wounds and breast cancers. Such extracts were also shown to stimulate cell proliferation including angiogenesis in the chick chorioallantoic membrane, now shown also for breast cancers. Removal of FbDP from plaque extracts by an anti-fibrinogen affinity column, or by an anti fragment E column, reduced activity. Human FbDP prepared in vitro were active, but not FgDP. Fibrin fragment E was active, and we also showed that admixture of FbDP with a polyclonal rabbit anti-fibrin E but not anti-fibrin D neutralized activity. However attempts to raise comparable monoclonal blocking antibodies were hindered by species similarities. The response of the Balb/c mouse was predominantly directed at minor D contaminants, in contrast to the Sprague-Dawley rat which responded to fibrin fragment E in our antigen preparation. PMID- 8457638 TI - Oxidized fibrin stimulates the activation of pro-urokinase and is the preferential substrate of human plasmin. AB - Activated phagocytes participate in physiological thrombolysis producing non radical excited oxidants and the important proteases elastase and urokinase. The interaction of oxidized fibrin with the proteases of the fibrinolytic system is therefore physiologically relevant. Here it is shown that human pro-urokinase is activated three- to four-fold faster in the presence of an oxidized solid fibrin matrix. In contrast, oxidized fibrin did not favour the fibrinolytic activity of urokinase or t-PA. Measurement of urokinase antigen showed that urokinase bound slightly to strongly oxidized denatured fibrin, whereas pro-urokinase did not. Plasmin degraded oxidized fibrin more rapidly than non-oxidized fibrin. Thus, singlet molecular oxygen (1O2) converts fibrin to a form that stimulates the activation of plasminogen (bound to oxidized fibrin) by pro-urokinase and that of pro-urokinase by plasmin. The oxidative modification of fibrin by 1O2 is specific. In contrast to oxygen radicals (H2O2 in high concentration) 1O2 does not directly destroy protein chains but favours subsequent fibrinolysis. Thus 1O2 prepares fibrin for its specific degradation. PMID- 8457639 TI - The susceptibility of plasma to activation of fibrinolysis. AB - The susceptibility of blood to fibrinolytic activation is an important parameter to predict the possible clinical outcome of thrombolysis in routine hospital practice. This paper describes a rapid method which is based on the integrated plasmin activity of a sample and which therefore does not require standardization of different fibrinolytic factors, such as plasminogen activator inhibitor type 1. Plasma is incubated with either streptokinase, urokinase (u-PA), tissue plasminogen activator (t-PA) or plasminogen streptokinase activator complex (PSAC) at room temperature. This is followed by addition of KCl, the chromogenic plasmin substrate S-2251 and chloramine T. As a blank, KCl is added before the enzyme. The incubation time is shortened three-fold at 37 degrees C. The highest fibrinolytic activity, with the smallest standard deviation, was obtained with streptokinase. When the lowest activity measured was defined as 100%, the highest activities were 273%, 297%, 344% and 961% for streptokinase, urokinase, t-PA and APSAC respectively. The susceptibility to urokinase correlated with that of t-PA. Patients reacted differently to the different plasminogen activators. Therefore, the method allows the appropriate agent and amount to be chosen before thrombolysis is started. PMID- 8457640 TI - Cellular fibronectin in plasma: its implications in fibrinogen-associated cryoprecipitation and other related reactions. AB - Elimination of cryoprecipitable plasma components (cryogels) by cryofiltration from the circulating blood of patients with drug-resistant rheumatoid arthritis (RA) alleviates clinical symptoms including morning stiffness and arthralgia. The cryogels thus isolated from the blood were found to consist mainly of fibrinogen (Fbg) and fibronectin (FN). Analysis by immunoblotting with an anti-cellular FN monoclonal antibody revealed that cellular FN (cFN) co-existed with plasma FN (pFN) in the cryogels derived from the patients. Using an ELISA, we assessed cFN together with the total FN (pFN+cFN) in plasmas and cryogels derived from the patients. The cFN/total FN ratio was distinctly higher in the cryogels than in the plasmas, suggesting that cFN was more readily precipitated than pFN in association with Fbg under cold conditions. PMID- 8457641 TI - The stimulatory capacity of soluble fibrin prepared from high and low molecular weight fibrinogen on plasminogen activation. AB - High molecular weight, low molecular weight and very low molecular weight fibrinogen were purified from human plasma, and converted partially or completely to fibrin by the action of thrombin or batroxobin. The stimulatory effects of these fibrin(ogen) preparations on plasminogen activation by tissue plasminogen activator were studied. When only 3-30% of the fibrinogen molecules were converted to fibrin, the high molecular weight fibrin had a greater stimulatory effect on plasminogen activation than equal amounts of low and very low molecular weight fibrin. In completely converted fibrin preparations, the plasminogen activating capacity of high molecular weight fibrin was either equal to (thrombin treated preparations) or greater than (batroxobin-treated preparations) that of very low molecular weight fibrin. These findings suggest that degradation of the A alpha-chain of fibrin does not per se increase its plasminogen activating capacity. PMID- 8457642 TI - Platelet adhesion to fibrin(ogen). AB - We have found that glycoprotein IIb:IIIa (GPIIb:IIIa) expressed on nonstimulated platelets is the primary receptor for platelet adhesion to immobilized fibrinogen or fibrin. At low shear rates of the blood the interaction between GPIIb:IIIa and fibrin(ogen) is strong enough to resist the shear forces exerted on the platelet as was shown with experiments with antibodies against platelet membrane glycoproteins and perfusion studies with blood from patients lacking platelet membrane receptors. Impaired platelet adhesion to fibrin(ogen) was found with blood from a patient with Glanzmann's thrombasthenia (lacking GPIIb:IIIa), blood from patients with the Bernard-Soulier syndrome (lacking GPIb) and blood from patients with severe von Willebrand's disease. This indicates that at higher shear rates additional interactions via GPIb on the platelet and von Willebrand factor originating from plasma or platelets are necessary to increase the affinity of the platelet for fibrin(ogen). PMID- 8457643 TI - Potent activity of peripheral blood lymphocytes in inducing hepatocyte stimulating factor and urokinase in monocytes. AB - As fibrinogen is an independent risk factor for arterial thrombosis we were interested in analysing the mechanism controlling fibrinogen biosynthesis. In this work, we showed that incubation of monocytes with lymphocytes increased hepatocyte stimulating factor (HSF) production. Different mechanisms are involved and our results demonstrated that this effect is in part mediated by an increase in interleukin 6 (IL-6) production. However, IL-6 cannot account for the whole effect and other cytokines could be implicated. In addition, we observed a stimulation of urokinase-type plasminogen activator (u-PA) associated with monocytes when these cells were incubated with lymphocytes for 18 h at 37 degrees C. By producing fragment D (fibrinogen degradation product) and D-dimer (fibrin degradation product) this fibrinolytic activity might also contribute to fibrinogen biosynthesis by hepatocytes. PMID- 8457644 TI - Incubation of monocytes with adriamycin increases secretion of hepatocyte stimulating factor for fibrinogen biosynthesis. AB - This work provides evidence that the production by monocytes of hepatocyte stimulating factor(s) for fibrinogen biosynthesis was dramatically increased when monocytes were exposed to Adriamycin. This effect was related to an increased production of leukaemia inhibiting factor (LIF), a cytokine known to stimulate fibrinogen biosynthesis by hepatic cells. Adriamycin also induces an increase in membrane-associated urokinase on monocytes. These results are consistent with the clinical observation in patients with ovarian cancer that when the CA-125 tumour marker decreases during chemotherapy, an increased level of D-dimer is a marker of good prognosis. PMID- 8457645 TI - Effects of glycosaminoglycans on factor XI activation by thrombin. AB - The recent observation that coagulation factor XI is activated by the serine protease thrombin indicates that factor XI may play a role in sustaining the haemostatic process by activating factor IX, after coagulation has been initiated by the factor VIIa/tissue factor catalytic complex. Since negatively charged substances, such as dextran sulphate or sulphatides, have been shown to enhance the activation of factor XI by thrombin, we investigated the effect of glycosaminoglycans on this reaction. A 60-fold enhancement in activation was observed in the presence of heparin and more modest increases were seen with dermatan sulphate and chondroitin sulphates A and C. The increase in activation was greater if Zn2+ was included in the reactions with glycosaminoglycans. The combination of heparin or chondroitin sulphate C and Zn2+ supported factor XI autoactivation in addition to factor XI activation by thrombin; an effect noted previously only with dextran sulphate. PMID- 8457646 TI - Automated determination of cross-linked fibrin derivatives in plasma. AB - Automated assays for the measurement of cross-linked fibrin derivatives in plasma (XL-FbDP) have been developed utilizing latex beads coated with anti-D dimer monoclonal antibody (DD-3B6/22) for both the Cobas Fara Chemistry Centrifugal and the Cobas Mira analysers (Roche, Basle, Switzerland). The analysers were programmed to mix plasma and latex reagent simultaneously and analyse absorbance changes over a 10-15 min period. Results were interpolated by the analyser from a standard curve derived from a polymer of D-dimer. Both assays had high precision (< 5% CV) for values between 100 and 1000 ng/ml and provided clear discrimination between normal samples and samples from patients suffering from the thrombotic diseases, DVT/PE and DIC. The results obtained for XL-FbDP determination with both methods compared well with established methods: a high correlation was obtained with a semi-quantitative manual latex method for both the Fara (r = 0.92) and Mira (r = 0.83) and correlations (r) of 0.81 (Fara) and 0.84 (Mira) were obtained with an enzyme immunoassay (EIA). Correlation between the two automated procedures was high (r = 0.96). The automated method will enable laboratories to provide a rapid and accurate quantitation of XL-FbDP. PMID- 8457647 TI - Elevated lipoprotein(a) is lowered by a cholesterol synthesis inhibitor in a normocholesterolaemic patient with premature myocardial infarction. AB - We have identified a 37-year-old patient suffering from two myocardial infarctions, with a markedly elevated lipoprotein(a) [Lp(a)] level and normal levels of cholesterol and triglycerides. Clinically this patient presented with xanthelasma and arcus lipoides corneae. After treatment with a cholesterol synthesis inhibitor (Pravastatin), the Lp(a) concentration in this patient was reduced significantly. This case report supports the hypothesis that elevated Lp(a) is an independent risk factor for coronary artery disease. The effect of the cholesterol synthesis inhibitor on Lp(a) may be due to the upregulation of the LDL-receptor, suggesting a role for LDL receptor in Lp(a) catabolism. PMID- 8457648 TI - First report of combined factor VII Padua defect and von Willebrand's disease due to casual association of the two defects. AB - We report a family with a combined factor VII Padua defect and von Willebrand's disease (vWd). The propositus is a 9-year-old child with a moderate bleeding tendency who appeared to be heterozygous for both factor VII Padua and type I vWd. The diagnosis of factor VII Padua was based on a normal factor VII antigen and factor VII activity which was low with rabbit brain thromboplastin but normal with ox brain thromboplastin. Type I vWd was diagnosed because of a concomitant decrease of von Willebrand factor antigen (vWf:Ag) and vWf ristocetin-cofactor activity (vWf:RCoF), associated with the presence of vWf multimers of all sizes in plasma and platelets. The parents were not consanguineous but came from the same isolated river Piave valley in North Eastern Italy where the factor VII Padua defect was first described. The father had the factor VII Padua defect but was clinically asymptomatic in accordance with the heterozygous state. The propositus's mother had type I vWd and was mildly symptomatic. The propositus' sisters, who were clinically asymptomatic, were both heterozygotes for factor VII Padua. The infusion of DDAVP normalized the factor VIII/vWf pattern in all patients. In the propositus, in contrast to the mother and normal subjects, showed a more rapid clearance both of vWf and factor VIII. The same pattern, albeit to a lesser degree, was also observed in the father. PMID- 8457649 TI - The effect of low dose nitroglycerin on plasma heparin concentrations and activated partial thromboplastin times. AB - We have investigated the effects of low dose nitroglycerin on the activated partial thromboplastin time (APTT), plasma heparin concentration, antithrombin III activity (AT-III) and platelet factor 4 (PF4) levels in a group of 42 patients receiving intravenous heparin and low dose nitroglycerin (GTN) following percutaneous transluminal coronary angioplasty (PTCA). Venous samples were taken before PTCA and at 2, 4 and 24 h after the start of the infusions. Despite the heparin infusion being constant, the median APTT ratio (interquartile range) was significantly lower at the 4 h sample time compared to the 2 h sample time (4.4 [3.8-4.5] vs 2.6 [1.8-4.0], P < 0.05). At this time there was also a significantly lower median plasma heparin concentration compared to the 2 h sample (0.35 [0.2-0.7] vs 0.17 [0.1-0.3] P < 0.05). There were no significant differences in AT-III activity or PF4 levels at 4 h compared to the 2 h sampling time. In another group of patients (n = 20) who received intravenous heparin alone following PTCA also at 1000 U/h there were no significant differences in median APTT ratios (4.4 [4.3-4.5] vs 4.2 [2.9-4.5]), or in median plasma heparin concentrations (0.26 [0.14-0.96] vs 0.22 [0.18-0.87]) at 4 h compared to 2 h. Our observations confirm that nitroglycerin can interfere with the anticoagulant effect of heparin even at low doses. Although the exact mechanism involved remains unknown, this study suggests it is likely to be a result of a reduction in plasma heparin levels, perhaps through acceleration of normal heparin elimination. PMID- 8457650 TI - Prolonged endurance exercise and blood coagulation: a 9 month prospective study. AB - To study the long-term overall effect of physical exercise on blood coagulation, 20 sedentary males and 15 sedentary females were trained three to four times a week with increasing intensity for 9 months. After 24 and 36 weeks all subjects ran a 15 km and a half-marathon (21 km) race, respectively. Blood samples were drawn before the training programme, 5 days before both races and 5 days after the half-marathon run. Plasma factor VIII coagulant activity and von Willebrand factor antigen concentration did not increase during the training programme. In both males and females plasma fibrinogen concentration was not enhanced after 24 weeks of training but increased in preparation for the 21 km race and was still raised significantly (P < 0.01) 5 days later. No significant changes in plasma thrombin-antithrombin III concentrations were observed in either group during the training programme. The results of this study demonstrate that an exercise programme of increasing intensity induces physical stress which has significant effects on plasma fibrinogen concentrations, even at rest. However, in contrast to acute post-exercise effects, a regular physical fitness programme does not induce a long-term activation of the haemostatic system. PMID- 8457651 TI - Bovine factor XIIa inhibitor. AB - Bovine factor XIIa inhibitor was purified by an improved method employing affinity for heparin. N-terminal amino acid sequencing revealed a unique sequence without homology to any other known protein sequences. Peptide sequencing, however, showed that a part of the bovine factor XIIa inhibitor was homologous to human C1-inhibitor with a fraction of identical amino acid residues around 70%. Deglycosylation studies and carbohydrate analysis showed the presence of N- and O linked carbohydrate. Bovine factor XIIa inhibitor did not inhibit plasma kallikrein and trypsin. The reactive site comprised an Arg-Asn bond, and represents the first example of asparagine as a P1' residue in Serpins with well documented inhibitory activity. PMID- 8457652 TI - Purification and characterization of recombinant human fibrinogen. AB - Our laboratory has been using protein engineering to study the relationship of primary structure to fibrinogen function. In order to examine genetically altered domains in the context of the intact, functional fibrinogen molecule, we have expressed recombinant human fibrinogen in Chinese Hamster Ovary (CHO) cells. The cDNA for each fibrinogen chain was individually cloned into the same expression vector. Each vector was cotransfected with the selection vector pRSVneo into CHO cells. In addition, the plasmids encoding A alpha and gamma were cotransfected with pRSVneo. Cells resistant to G418, a neomycin analogue, were isolated and clonal lines developed. Analysis of these lines demonstrated that CHO cells express and secrete free gamma chain, and an A alpha-gamma complex. To obtain recombinant fibrinogen, the A alpha-gamma G418-resistant clones were transfected with the B beta expression plasmid and a second selection vector, pMSVhis. Colonies resistant to neomycin and histidinol were selected and clonal lines obtained. These clones secreted biologically active recombinant human fibrinogen, which was purified from serum-free culture media by protamine-Sepharose chromatography. Analysis of the purified protein on SDS-polyacrylamide gels demonstrated a pattern indistinguishable from plasma fibrinogen. Removal of Asn linked carbohydrate with glycosidase F revealed the presence of carbohydrate on the B beta and gamma chains, as is seen for plasma fibrinogen. PMID- 8457653 TI - The polymerization of fibrinogen Dusart (A alpha 554 Arg-->Cys) after removal of carboxy terminal regions of the A alpha-chains. AB - The six polypeptide chains of normal fibrinogen are covalently linked by interchain disulphide bonds, and there are no free sulphydryl groups. Fibrinogen Dusart is a congenital fibrinogen variant in which A alpha 554 Arg is replaced by Cys; albumin is disulphide linked to these fibrinogen molecules, possibly at A alpha 554 Cys. Functionally, Dusart fibrinogen displays markedly abnormal fibrin polymerization, characterized by delayed lateral fibril association and matrix fibre bundles that are thinner than normal fibrin bundles. These observations are consistent with experiments suggesting that the carboxy terminal region of the A alpha-chain contains a polymerization domain that participates in lateral fibril associations. In order to investigate the location and the effect of albumin binding to Dusart fibrinogen, we examined the fibrinogen by electron microscopy, and compared the polymerization and ultrastructure of fibrin prepared from normal fibrinogen containing intact A alpha-chains (fraction I-2) or plasmin degraded fibrinogen molecules lacking carboxy terminal regions of A alpha-chains (fraction I-9D), with fibrin prepared from Dusart fraction I-2 and I-9D. Most bound albumin was released from Dusart fibrinogen by plasmin degradation involving the A alpha chains. Nevertheless, we were able to visualize albumin molecules remaining covalently bound to Dusart I-9D as well as to Dusart I-2 fibrinogen, as distinct globular domains situated near the fibrinogen D domain. The presence of albumin in these fractions was confirmed by Western blotting using anti-albumin. Dusart fibrin polymerized much more slowly than normal I-2, as previously reported, whereas polymerization of Dusart I-9D fibrin was faster than Dusart I-2 and nearly the same as normal I-9D fibrin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457654 TI - Unusual A alpha 16Arg-->Cys dysfibrinogenaemic family: absence of normal A alpha chains in fibrinogen from two of four heterozygous siblings. AB - We describe studies of fibrinogen from an asymptomatic family, Fibrinogen Frankfurt XIII, with the substitution A alpha 16Arg-->Cys. The mother's fibrinogen was normal as assessed by plasma fibrinogen assays but the father and four children were affected. Two affected siblings and their father had thrombin times approximately 20 s longer than controls, fibrinogen of 35-52 mg/dl by clotting assay and normal levels by immunoassay. Measured by HPLC their fibrinogen had decreased amounts of releasable fibrinopeptide A (FpA) relative to normal controls. In addition, their fibrinogen was partly coagulable with batroxobin and fully coagulable with thrombin; consistent with its incomplete FpA release. In contrast, plasma from the other two siblings had thrombin times > 2 min longer than controls, and their fibrinogen was < 10 mg/dl by clotting assay and normal by immunoassay. Their isolated fibrinogen did not release FpA (n = 5) and formed thrombin clots only at cold temperatures indicating formation of desBB fibrin. Assessed by SDS-PAGE, only monomeric fibrinogen was seen in isolated fibrinogen, washed and unreduced plasma immunoprecipitates, non-crosslinked plasma clots or 56 degrees C precipitates. DNA sequencing of PCR products using oligonucleotide primers which flanked sequences coding for A alpha 7Asp to 35Phe, disclosed mutant (C-->T, coding for A alpha 16Cys) and wild type alleles present in both severely affected siblings. It is concluded that circulating fibrinogen contained only mutant FpA. A possible second mutation, not apparent from plasma assays on the mother, is believed to account for the absence of releasable normal FpA in circulating fibrinogen. PMID- 8457655 TI - Inhibition of concomitant thrombin-mediated fibrin formation enhances clot lysis in whole blood. AB - To characterize potential mechanisms for enhanced thrombolysis in the presence of thrombin inhibitors, we measured lysis of 125I-fibrin-(ogen)- labelled clots after incubation in rotating tubes with whole blood containing tissue-type plasminogen activator (t-PA, 1500 ng/ml) and either saline or increasing concentrations of recombinant desulphatohirudin (hirudin), or heparin. Thrombin activity in washed clots was negligible, but incubation of clots with t-PA in non anticoagulated blood resulted in marked thrombin activity within 5 min as measured by fibrinopeptide A generation. Incubation with hirudin over a range of concentrations increased clot lysis compared with t-PA alone (control) from 132 +/- 18% of control with 0.5 microgram/ml (n = 4) to 216 +/- 48% of control with 10 micrograms/ml (n = 4). Incubation with less than 0.5 U/ml of heparin attenuated clot lysis (35 +/- 22% of control with 0.08 U/ml, n = 3) while concentrations > or = 0.5 U/ml increased lysis (178 +/- 13% of control with 1.7 U/ml, n = 4). Similar results were obtained for incubations in recalcified platelet-poor plasma indicating that platelets are not required for the enhancement of clot lysis induced by thrombin inhibitors. However, incubations in recalcified plasma from a patient with afibrinogenaemia abolished the increased lysis observed with 10 micrograms/ml of hirudin and addition of physiological concentrations of fibrin monomer (400-800 nM) or fibrinogen degradation products (500 nM) to the mixture of whole blood, t-PA and hirudin blunted the extent of clot lysis. Thus, inhibition of thrombin activity induced by exposure of clots to t-PA prevents concomitant formation of fibrin that attenuates fibrinolysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457656 TI - Kinetic and mechanical parameters of pure and cryoprecipitate fibrin. AB - The kinetics of formation (clot time; CT) as well as a mechanical parameter (breaking strength; BS) of fibrin were measured at various concentrations of fibrinogen. In a pure system and for a fixed level of thrombin, the CT-fibrinogen dependency was biphasic, reaching a minimum in the range 1-8 microM fibrinogen. A new parameter, [Fib]min, the minimal fibrinogen concentration required for phase change, was derived from this. The [Fib]min values of pure fibrinogen activated with thrombin, ranged between 0.15 and 0.25 microM fibrinogen. Single donor cryoprecipitate (cryo) had similar kinetics and [Fib]min value. A technique for measuring the innate breaking strength of fibrin, independently of its adhesive properties, is described. For pure fibrin activated with thrombin, the BS was a linear function of fibrinogen concentration, with numeric values for the slope of 0.84 g/microM and slopeCa (with 2.5 mM Ca) of 2.26 g/microM, which transformed into a general description of the BS of fibrin and the fibrinogen level according to the equation: BS = mu [Fib]. The constants mu = 18.9 dyne/microM-cm2 and microCa = 55.7 dyne/microM-cm2 reflect the innate strength of fibrin clot per cross-section area. Cryo fibrin exhibited a BS equivalent to its fibrinogen level in a pure system. Although scanning electron microscopy of pure and cryo fibrin formed at equivalent fibrinogen levels revealed significant ultrastructural disparity between the pure and cryo fibrin, the kinetics of formation and the mechanical parameters of both were comparable. PMID- 8457657 TI - Binding of a new monoclonal antibody against N-terminal heptapeptide of fibrin alpha-chain to fibrin polymerization site 'A': effects of fibrinogen and fibrinogen derivatives, and pretreatment of samples with NaSCN. AB - A novel murine monoclonal antibody against the fibrin alpha-chain N-terminus is presented, which reacts with desAA- and desAABB-fibrin. In immunoblot procedures, the antibody reacted with fibrin degradation products X and Y of non-crosslinked fibrin, and fragment E. No binding was observed to the fibrin fragment D-dimer, and fibrinogen fragments D and E. Minor binding to fibrinogen fragments X, and Y, and desBB-fibrin were presumably due to minor contamination with (desAA)-fibrin. A prerequisite for binding was release of fibrinopeptides A (FpA), the binding site being a fibrin-specific neo-epitope. No binding was observed to fibrinogen or to thrombin-treated dysfibrinogen MANNHEIM III (A alpha 16 Arg-->Cys) molecules, which do not release FpA. The antibody bound to abnormal fibrin molecules prepared from dysfibrinogen MANNHEIM I (A alpha 19 Arg-->Gly), albeit to a lesser extent than to normal fibrin. Binding of the antibody to the fibrin epitope was greatly enhanced by denaturation, e.g. by heat, or by treatment with chaotropic ions. Soluble fibrin in clinical samples is generally found as a complex with fibrinogen, since polymerization sites 'A' exposed by release of FpA react with complementary binding sites 'a' on the D-domains of other fibrin and fibrinogen molecules. Treatment of samples with NaSCN caused dissociation of fibrin monomer complexes. Reassociation was prevented by denaturation of both polymerization sites 'A' and 'a'. The antibody in combination with NaSCN treatment of samples was useful for specific detection of fibrin monomer in plasma samples. Measurement was not influenced by fibrinogen degradation products, whereas fibrin degradation products at very high concentration caused some underestimation of fibrin monomer concentration. PMID- 8457658 TI - GPR-phoresis, a novel approach to determining fibrin monomer and other macromolecular derivatives of fibrinogen and fibrin in blood. AB - An electrophoretic method for determining (i) cross-linked fibrin-complexes, (ii) fibrin-monomer, (iii) fibrinogen-dimers, (iv) normal fibrinogen and (v) degradation products in plasma, has been devised. The technique is based on differences in their migration characteristics in the presence and absence of Gly Pro-Arg (GPR), a specific inhibitor of fibrin aggregation. In buffer containing 2.5 mM GPR, fibrin monomer and fibrinogen co-migrate anodally, but, unlike fibrinogen which does not depend on GPR for solubility, the fibrin monomers precipitate when they traverse a boundary between buffer containing and buffer lacking GPR. By limiting the GPR to a 2 cm zone of buffer under the conditions employed, the precipitation of fibrin monomer occurs in a sharp band 4 mm anodally to the sample application point. Cross-linked fibrin complexes have slower mobility than fibrin monomer and precipitate in a broad band behind the monomer. Dimeric fibrinogen, like fibrinogen itself but unlike the fibrin complexes, is not constrained to migration within the GPR boundary and passes through it, but behind the band for normal fibrinogen due to sieving by the gel. Fibrinogen and all but low molecular weight degradation products can be specifically precipitated within electrophoregrams by heat denaturation at 47 degrees C. After washing unrelated protein away, the fibrin(ogen) derivatives can be measured by staining with Coomassie blue. Since the method does not depend on immunoprobing for specific staining, it provides an inexpensive and rapid means for differential assessment of the prevalence of the fibrinogen derivatives in disease states and in models of disease, regardless of animal species. PMID- 8457659 TI - Soluble fibrin as a molecular marker for a pre-thrombotic state: a mini-review. AB - Increased plasma levels of soluble fibrin are considered as molecular markers of an impending thrombotic event. Several methods to assess soluble fibrin have been in existence for many years. Most of those methods are nonspecific, semiquantitative or too laborious to be used in clinical practice. More recent methods are quantitative and relatively rapid. Some of those methods may, however, not be fully specific; in other cases clinical experience is lacking. PMID- 8457660 TI - A new immunoassay for soluble fibrin enables a more sensitive detection of the activation state of blood coagulation in vivo. AB - A novel sandwich immunoassay for measurement of soluble fibrin in plasma has been developed. For immunization we used the synthetic heptapeptide Gly-Pro-Arg-Val Val-Glu-Arg representing the amino terminus of the alpha-chain of human fibrin. A monoclonal IgG1 antibody was obtained by conventional hybridoma technology. To increase convenience, the sandwich immunoassay was developed for the Enzymun-Test systems which are based on streptavidin pre-coated tubes. The new assay was designed with the same fibrin specific antibody both in biotinylated and in peroxidase-labelled form. Fibrin in native plasma samples could only be detected after pre-incubation of the plasma with chaotropic ions. Test results were calculated using a standard curve comprising six fibrin standards (0-50 micrograms/ml). Precision of the method was satisfactory; intra-assay CVs using plasma samples ranged between 5.0% (23.7 micrograms/ml) and 12.4% (0.2 microgram/ml). CVs of interassay precision measurements using standards as samples range between 7.3% (25.0 micrograms/ml) and 11.4% (1.0 micrograms/ml). The lower detection limit was 0.12 microgram/ml. Investigations of normal range in 70 age-matched healthy individuals resulted in a mean of 1.12 micrograms/ml. Linearity was excellent; recovery of high fibrin plasma after dilution with normal plasma was always between 100 and 107%. Fibrin specificity was due to the monoclonal antibody 2B5 used and no cross reactivity with fibrinogen, fibrinogen split products or fibrin D-dimer was observed. Fibrin fragment E1 (studied by Dempfle CE, et al. Blood Coag Fibrinol 1993; 4: 79-86) and fragments X and Y showed moderate cross reactivity in the assay and caused some overestimation of fibrin at high fibrin split product concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457661 TI - Connectivity of membrane domains. PMID- 8457662 TI - A new computational method for cable theory problems. AB - We discuss a new computational procedure for solving the linear cable equation on a tree of arbitrary geometry. The method is based on a simple set of diagrammatic rules implemented using an efficient computer algorithm. Unlike most other methods, this technique is particularly useful for determining the short-time behavior of the membrane potential. Examples are presented and the convergence and accuracy of the method are discussed. PMID- 8457663 TI - Solution structure and dynamics of cyclic and acyclic cholinergic agonists. AB - Two classes of nicotinic cholinergic agonists, which vary in flexibility and electronegativity, have been synthesized, and their structural and dynamic properties have been studied with nuclear magnetic resonance (NMR) spectroscopy. Although the compounds are chemically identical except for the presence or absence of one cyclicizing C--C bond, single channel recording and radioligand binding studies have shown that the cyclic compounds are considerably more potent than the acyclic derivatives (McGroddy, K.A., A.A. Carter, M.M. Tubbert, and R.E. Oswald. 1993. Biophys. J. 64:325-338). Using one- and two-dimensional NMR spectroscopy, we have shown that these molecules exist in two distinct stable conformers, which differ in the orientation of the amide bond. The cyclic 1,1 dimethyl-4-trifluoroacetyl-piperazinium iodide and its trifluoromethyl derivative compounds are symmetric, and the two conformers are of equal energy. The acyclic N,N,N,N'-tetramethyl-N'-acetylethylene-diamine iodide (TED) and its trifluoromethyl derivative derivatives, however, populate two energetically unequal solution conformations. Using variable temperature NMR spectroscopy on these molecules and their uncharged precursors, we have characterized the energetics of amide bond isomerization and have distinguished steric and electrostatic contributions to the equilibrium between the two conformers. The more populated TED conformer has the amide methyl group trans to the carbonyl oxygen, and it is stabilized by an electrostatic attraction between the partially negative carbonyl oxygen and the positively charged quaternary amine nitrogen. As discussed in the accompanying paper (McGroddy, K.A., A.A. Carter, M.M. Tubbert, and R.E. Oswald. 1993. Biophys. J. 64:325-338), the differences in the stable solution structures of the TED derivatives and their interconversion kinetics may be of biological significance. PMID- 8457665 TI - Torsion angle analysis of glycolipid order at membrane surfaces. AB - A method is presented for determining the average glycosidic torsion angles and motion about those angles for a glycolipid headgroup at a model membrane surface. Dipolar and quadrupolar coupling constants were previously collected on the headgroup of beta-dodecyl glucoside embedded in phospholipid/detergent bilayers which orient in a magnetic field (Sanders, C.R., and J.H. Prestegard. 1991. J. Am. Chem. Soc. 113:1987-1996). These observables are expressed as averages of second order spherical harmonics, and Wigner rotation matrices are used here to transform the spherical harmonics from the laboratory frame to a set of frames which allow motional averaging to be described as the result of simple bond rotations. Euler angles corresponding to rotations about glycosidic torsion angles phi and psi are chosen to best reproduce experimental coupling constants, using models which have varying degrees of motional averaging. These models include a rigid headgroup, axially symmetric headgroup motion, and independent motion about each torsion angle in a square well potential. The square well model proves to be significantly better than the rigid model in reproducing experimental observations and it offers a more physically meaningful description of motion than the axially symmetric model. The structures obtained, assuming a square well potential, are compared to potential energy maps for the glycolipid torsional angles to illustrate the need for inclusion of the membrane interface in energetic modeling of glycolipid conformations. PMID- 8457664 TI - Analysis of cyclic and acyclic nicotinic cholinergic agonists using radioligand binding, single channel recording, and nuclear magnetic resonance spectroscopy. AB - The relationship between the structure and function of a series of nicotinic cholinergic agonists has been studied using radioligand binding, single channel recording, and nuclear magnetic resonance spectroscopy. The cyclic compound 1,1 dimethyl-4-acetylpiperazinium iodide and its trifluoromethyl analogue (F3-PIP) interact with nicotinic acetylcholine receptors (nAChRs) from both Torpedo electroplaque and BC3H-1 cells at lower concentrations than the acyclic derivatives, N,N,N,N'-tetramethyl-N'-acetylethylenediamine iodide and its fluorinated analogue (F3-TED). The magnitude of the difference in potencies depends on the type of measurement. In binding experiments, the differences between the two classes of compounds depends mainly on the conditions of the experiment. In measurements of the initial interaction with the nAChR, the PIP compounds have an affinity approximately one order of magnitude higher than that of the TED compounds. Longer incubations indicated that the PIP compounds were able to induce a time-dependent shift in receptor affinity consistent with desensitization, whereas the TED compounds were unable to induce such a shift. The activation of single channel currents by the cyclic compounds occurs at concentrations approximately two orders of magnitude lower than for the acyclic compounds, but the TED compounds exhibit a larger degree of channel blockade than the PIP compounds. Previous work (McGroddy, K.A., and R.E. Oswald. 1992. Biophys. J. 64:314-324) has shown that the TED compounds can exist in two energetically distinct conformational states related by an isomerization of the amide bond. 19F nuclear magnetic resonance experiments suggest that the higher energy population of the TED compounds may interact preferentially with the ACh binding sites on the nAChRs and that a significant fraction of the difference between the initial affinity of the PIP and TED compounds may be accounted for by the predominance in solution of a conformational state less able to interact with the ACh binding sites on nAChRs. PMID- 8457666 TI - Percolation and diffusion in three-component lipid bilayers: effect of cholesterol on an equimolar mixture of two phosphatidylcholines. AB - The lateral diffusion of a phospholipid probe is studied in bilayers of binary mixtures of dimyristoylphosphatidylcholine (DMPC)/cholesterol and distearoylphosphatidylcholine (DSPC)/cholesterol and in the ternary system DMPC/DSPC/cholesterol using fluorescence recovery after photobleaching. An approximate phase diagram for the ternary system, as a function of temperature and cholesterol concentration, was obtained using differential scanning calorimetry and the phase diagrams of the binary systems. This phase diagram is similar to those of the phospholipid/cholesterol binary mixtures. In bilayers where solid and liquid phases coexist, the diffusion results are interpreted in terms of phase percolation. The size of the liquid-phase domains is estimated using percolation theory. In the ternary system, addition of cholesterol up to approximately 20 mol% shifts the percolation threshold to lower area fractions of liquid, but the size of the liquid-phase domains does not change. Above approximately 20 mol% cholesterol, the liquid phase is always connected. The size of solid-phase domains clusters is estimated using a model recently developed (Almeida, P.F.F., W.L.C. Vaz, and T.E. Thompson. 1992. Biochemistry. 31:7198 7210). For cholesterol concentrations up to 20 mol%, the size of solid-phase domain units does not change. Beyond 20 mol%, cholesterol causes the size of the solid units to decrease. PMID- 8457667 TI - Nonideal mixing of phosphatidylserine and phosphatidylcholine in the fluid lamellar phase. AB - The mixing of phosphatidylserine (PS) and phosphatidylcholine (PC) in fluid bilayer model membranes was studied by measuring binding of aqueous Ca2+ ions. The measured [Ca2+]aq was used to derive the activity coefficient for PS, gamma PS, in the lipid mixture. For (16:0, 18:1) PS in binary mixtures with either (16:0, 18:1)PC, (14:1, 14:1)PC, or (18:1, 18:1)PC, gamma PS > 1; i.e., mixing is nonideal, with PS and PC clustered rather than randomly distributed, despite the electrostatic repulsion between PS headgroups. To understand better this mixing behavior, Monte Carlo simulations of the PS/PC distributions were performed, using Kawasaki relaxation. The excess energy was divided into an electrostatic term Uel and one adjustable term including all other nonideal energy contributions, delta Em. Uel was calculated using a discrete charge theory. Kirkwood's coupling parameter method was used to calculate the excess free energy of mixing, delta GEmix, hence In gamma PS,calc. The values of In gamma PS,calc were equalized by adjusting delta Em in order to find the simulated PS/PC distribution that corresponded to the experimental results. We were thus able to compare the smeared charge calculation of [Ca2+]surf with a calculation ("masked evaluation method") that recognized clustering of the negatively charged PS: clustering was found to have a modest effect on [Ca2+]surf, relative to the smeared charge model. Even though both PS and PC tend to cluster, the long-range nature of the electrostatic repulsion reduces the extent of PS clustering at low PS mole fraction compared to PC clustering at an equivalent low PC mole fraction. PMID- 8457668 TI - Mechanical properties of vesicles. I. Coordinated analysis of osmotic swelling and lysis. AB - To determine how transmembrane osmotic gradients perturb the structure and dynamics of biological membranes, we examined the effects of medium dilution on the structures of osmolyte-loaded lipid vesicles. Our preparations were characterized by dynamic light scattering (DLS) and nuclear magnetic resonance (NMR) spectroscopies. Populations of Escherichia coli phosphatidylethanolamine (PE) or dioleoylphosphatidylglycerol (DOPG) vesicles prepared by the pH jump technique were variable and polymodal in size distribution. Complex and variable structural changes occurred when PE vesicles were diluted with hypotonic buffer. Such vesicles could not be used as model systems for the analysis of membrane mechanical properties. NaCl-loaded, DOPG vesicles prepared by extrusion through 100 nm (diameter) pores were reproducible and monomodal in size distribution and unilamellar, whereas those prepared by extrusion through 200-, 400-, or 600-nm pores were variable and polymodal in size distribution and/or multilamellar. Time and pressure regimes associated with osmotic lysis of extruded vesicles were defined by monitoring release of carboxyfluorescein, a self-quenching fluorescent dye. Corresponding effects of medium dilution on vesicle structure were assessed by DLS spectroscopy. These experiments and the accompanying analysis (Hallett, F.R., J. Marsh, B.G. Nickel, and J.M. Wood. 1993. Biophys. J. 64:000-000) revealed conditions under which vesicles are expected to reside in a consistently strained state. PMID- 8457669 TI - Mechanical properties of vesicles. II. A model for osmotic swelling and lysis. AB - Vesicle polydispersity and leakage of solutes from the vesicle lumen influence the measurement and analysis of osmotically induced vesicle swelling and lysis, but their effects have not been considered in previous studies of these processes. In this study, a model is developed which expressly includes polydispersity and leakage effects. The companion paper demonstrated the preparation and characterization of large unilamellar lipid vesicles. A dye release technique was employed to indicate the leakage of solutes from the vesicles during osmotic swelling. Changes in vesicle size were monitored by dynamic light scattering (DLS). In explaining the results, the model identifies three stages. The first phase involves differential increases in membrane tension with strain increasing in larger vesicles before smaller ones. In the second phase, the yield point for lysis (leakage) is reached sequentially from large sizes to small sizes. In the final phase, the lumen contents and the external medium partially equilibrate under conditions of constant membrane tension. When fit to the data, the model yields information on polydispersity-corrected values for membrane area compressibility, Young's modulus, and yield point for lysis. PMID- 8457670 TI - Osmotic properties of large unilamellar vesicles prepared by extrusion. AB - We have examined the morphology and osmotic properties of large unilamellar vesicles (LUVs) prepared by extrusion. Contrary to expectations, we observe by cryo-electron microscopy that such vesicles, under isoosmotic conditions, are non spherical. This morphology appears to be a consequence of vesicle passage through the filter pores during preparation. As a result when such LUVs are placed in a hypoosmotic medium they are able to compensate, at least partially, for the resulting influx of water by "rounding up" and thereby increasing their volume with no change in surface area. The increase in vesicle trapped volume associated with these morphological changes was determined using the slowly membrane permeable solute [3H]-glucose. This allowed calculation of the actual osmotic gradient experienced by the vesicle membrane for a given applied differential. When LUVs were exposed to osmotic differentials of sufficient magnitude lysis occurred with the extent of solute release being dependent on the size of the osmotic gradient. Surprisingly, lysis was not an all-or-nothing event, but instead a residual osmotic differential remained after lysis. This differential value was comparable in magnitude to the minimum osmotic differential required to trigger lysis. Further, by comparing the release of solutes of differing molecular weights (glucose and dextran) a lower limit of about 12 nm diameter can be set for the bilayer defect created during lysis. Finally, the maximum residual osmotic differentials were compared for LUVs varying in mean diameter from 90 to 340 nm. This comparison confirmed that these systems obey Laplace's Law relating vesicle diameter and lysis pressure. This analysis also yielded a value for the membrane tension at lysis of 40 dyn cm-1 at 23 degrees C, which is in reasonable agreement with previously published values for giant unilamellar vesicles. PMID- 8457672 TI - A solid-state 31P-NMR investigation of the allosteric transition in glycogen phosphorylase b. AB - The catalytic role of the cofactor phosphate moiety at the active site of glycogen phosphorylase has been the subject of many investigations including solution-state high-resolution 31P-NMR studies. In this study the pyridoxal phosphate moiety in both the inactive and active forms of microcrystalline phosphorylase b has been investigated by high-resolution 31P magic-angle spinning NMR. The symmetry of the shielding tensor in model compounds at varying degrees of ionization is investigated and the results indicate a marked difference between the dianionic and monoanionic model compounds. Consequently the observed similarity in the principal tensor components describing the shielding tensor of the phosphorus nuclei present at the active site of both the R- and T-state conformations suggests that there is no change in ionization site upon activation in contrast to suggestions based upon isotropic shifts. Since previous relaxation measurements have pointed to the need to consider motional influences in such systems, several plausible models are considered. Subject to the assumption of congruency between the principal axis system describing the shielding interaction and molecular frame determined by the molecular symmetry axes, we conclude that the phosphate cofactor is dianionic in both forms. PMID- 8457671 TI - Direct visualization by electron microscopy of the weakly bound intermediates in the actomyosin adenosine triphosphatase cycle. AB - We used a novel stopped-flow/rapid-freezing machine to prepare the transient intermediates in the actin-myosin adenosine triphosphatase (ATPase) cycle for direct observation by electron microscopy. We focused on the low affinity complexes of myosin-adenosine triphosphate (ATP) and myosin-adenosine diphosphate (ADP)-Pi with actin filaments since the transition from these states to the high affinity actin-myosin-ADP and actin-myosin states is postulated to generate the molecular motion that drives muscle contraction and other types of cellular movements. After rapid freezing and metal replication of mixtures of myosin subfragment-1, actin filaments, and ATP, the structure of the weakly bound intermediates is indistinguishable from nucleotide-free rigor complexes. In particular, the average angle of attachment of the myosin head to the actin filament is approximately 40 degrees in both cases. At all stages in the ATPase cycle, the configuration of most of the myosin heads bound to actin filaments is similar, and the part of the myosin head preserved in freeze-fracture replicas does not tilt by more than a few degrees during the transition from the low affinity to high affinity states. In contrast, myosin heads chemically cross linked to actin filaments differ in their attachment angles from ordered at 40 degrees without ATP to nearly random in the presence of ATP when viewed by negative staining (Craig, R., L.E. Greene, and E. Eisenberg. 1985. Proc. Natl. Acad. Sci. USA. 82:3247-3251, and confirmed here), freezing in vitreous ice (Applegate, D., and P. Flicker. 1987. J. Biol. Chem. 262:6856-6863), and in replicas of rapidly frozen samples. This suggests that many of the cross-linked heads in these preparations are dissociated from but tethered to the actin filaments in the presence of ATP. These observations suggest that the molecular motion produced by myosin and actin takes place with the myosin head at a point some distance from the actin binding site or does not involve a large change in the shape of the myosin head. PMID- 8457673 TI - Solid state 31P cross-polarization/magic angle sample spinning nuclear magnetic resonance of crystalline glycogen phosphorylase b. AB - (31)P cross-polarization/magic angle sample spinning nuclear magnetic resonance spectra have been obtained for pyridoxal 5'-phosphate (PLP) bound to glycogen phosphorylase b (GPb) in two different crystalline forms, monoclinic and tetragonal. Analysis of the intensities of the spinning sidebands in the nuclear magnetic resonance spectra has enabled estimates of the principal values of the (31)P chemical shift tensors to be obtained. Differences between the two sets of values suggest differences in the environment of the phosphate moiety of the pyridoxal phosphate in the two crystalline forms. The tensor for the tetragonal crystalline form, T state GPb, is fully consistent with those found for dianionic phosphate groups in model compounds. The spectrum for the monoclinic crystalline form, R state GPb, although closer to that of dianionic than monoanionic model phosphate compounds, deviates significantly from that expected for a simple dianion or monoanion. This is likely to result from specific interactions between the PLP phosphate group and residues in its binding site in the protein. A possible explanation for the spectrum of the monoclinic crystals is that the shift tensor is averaged by a proton exchange process between different ionization states of the PLP associated with the presence of a sulfate ion bound in the vicinity of the PLP. PMID- 8457674 TI - Structure of beta-crystallite assemblies formed by Alzheimer beta-amyloid protein analogues: analysis by x-ray diffraction. AB - To elucidate the relation between amyloid fibril formation in Alzheimer disease and the primary structure of the beta/A4 protein, which is the major component of the amyloid, we have been investigating the ability of peptides sharing sequences with beta/A4 to form fibrils in vitro. In previous studies we focused on the macroscopic morphology of the assemblies formed by synthetic peptides corresponding in sequence to different regions of this protein. In the present study we analyze the x-ray diffraction patterns obtained from these assemblies. All specimens showed wide angle reflections that could be indexed by an orthogonal lattice of beta-crystallites having unit cell dimensions a = 9.4 A, b = 7 A, and c = 10 A, where a refers to hydrogen bonding direction, b to polypeptide chain direction, and c to intersheet direction. Given the amino acid sequence of beta/A4 as NH2-DAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIAT-COOH, we found that, based on their orientation and assembly, the analogues could be classified into three groups: Group A, residues 19-28, 13-28, 12-28, 11-28, 9-28, 1-28, 1-38, 1-40, 6-25, 11-25 and 34-42; Group B, residues 18-28, 17-28, and 15 28; and Group C, residues 22-35 and 26-33. For Groups A and C, the sharpest reflections were (h00), indicating that the assemblies were fibrillar, i.e., elongated in a single direction. Lateral alignment of the crystallites in Group A account for its cross-beta pattern, in which the hydrogen bonding (H-bonding) direction is the fiber (rotation) axis. By comparison, the beta-crystallites of Group C had no preferential orientation, thus giving circular scattering. For Group B, the sharpest reflections were (h0l) on the meridian, indicating that the assemblies were plate-like, i.e., extended in two directions. A series of equatorial Bragg reflections having a 40 A period indicated regular stacking of the plates, and the rotation axis was normal to the surface of the plates. Of the Group A peptides, the analogues 11-28 and 6-25 showed intensity maxima on the equator as well as on higher layer lines, indicating that the beta-crystallites are highly ordered relative to one another in the axial, H-bonding direction. This sampling of the layer lines by a larger period (60 A) suggests that the beta crystallites are arrayed either in cylindrical or small restricted crystalline lattices. Consistent with its electron microscopic images, we modeled the structure as a tube with five or six f,-crystallites constituting the wall and with the individual crystallite, which either rotates freely or is restricted, made of five or fewer beta-pleated sheets. For the Group B peptides, the electron density projection along the b-axis was calculated from the observed intensities using phase combinations from fl-keratin.Amino acid side-chain positions were apparent and, when refined as 4-A-diameter spheres, led to a substantial decrease in the R-factors.For peptide 18-28 the electron density peaks, which are thought to correspond to side chains, were centered 3.3 A from the peptide backbone, whereas for peptides 17-28 and 15-28, these peaks were centered 1 A or more further from the backbone. Peaks having high electron density faced peaks having lower density, suggesting a favorable stereochemical arrangement of the residues. Thus, our analysis of the fiber x-ray patterns from beta/A4 peptides shows the organization of the beta-crystallites that form the wall of the amyloid fibrils as well as possible side-chain interactions. PMID- 8457675 TI - X-ray small angle scattering of the human transferrin protein aggregates. A fractal study. AB - X-ray small angle scattering experiments, using a pin hole SAXS camera with Synchrotron radiation source, have been performed to study the conformational changes of lyophilized samples of Apo-, Mono-, and Diferric- human transferrin. We report the experimental evidence that the analysis of the scattered intensity through the fractal theory may give information on the particle size and its variation upon iron binding. PMID- 8457676 TI - Elemental composition of secretory granules in pancreatic islets of Langerhans. AB - We have characterized, by electron probe microanalysis, rapidly frozen cultured rat islets at the level of individual secretory granules. Elemental analysis of thin, dried cryosections showed that beta granules could be distinguished by high Zn, Ca, and S, whereas non-beta (mainly alpha) granules contained elevated P and Mg. Although a single granule type predominated in a particular cell, some rebel granules were found in A cells that had the compositional fingerprint of B cell granules. Zn, which was found in millimolar concentrations in B cell granules, was considered a marker for the insulin storage complex. The data indicate that non-B islet cells in the adult pancreas may produce insulin-containing organelles and that, when glucagon and insulin are coexpressed, these hormones are packaged in separate granules. PMID- 8457677 TI - Optical trapping for chromosome manipulation: a wavelength dependence of induced chromosome bridges. AB - Using a tunable titanium-sapphire laser, we have compared different wavelengths (from 700 to 840 nm) for their utility in optical trapping of chromosomes in mitotic rat kangaroo Potorous tridactylus (PtK2) cells. It was found that irradiation with a near-infrared light induces the sticking together of chromosome shoulders. The attached chromatids failed to separate, or separated with significant delay and formed a chromosome bridge during anaphase. Using this bridge (and induced c-mitosis) as a reference, we compared the action of different wavelengths (from 700 to 840 nm). Chromosomes were irradiated at metaphase and the cells were observed until the end of cytokinesis. Chromosomes were irradiated for different periods of time, using 130 mW of power at the objective focal plane. The biological responses observed after optical trapping were: (1) normal cell division, (2) formation of a temporary chromosome bridge, (3) formation of a permanent chromosome bridge, (4) complete blockage of chromosome separation (c-mitosis). The chromosomes were found to have a maximal sensitivity to 760-765 nm light and minimal sensitivity to 700 and 800-820 nm light. Cells with chromosomes irradiated for a long time, using wavelength 760 765 nm, generally were incapable of going through anaphase and remained in c mitosis. We conclude that the optimal wavelengths for optical trapping are 700 and 800-820 nm. PMID- 8457678 TI - Observation of living cells using the atomic force microscope. AB - We used an atomic force microscope (AFM) to image samples immersed in a fluid in order to study the dynamic behavior of the membranes of living cells. AFM images of cultured cells immersed in a buffer were obtained without any preliminary preparation. We observed surface changes and displacements which suggest that the cells were still alive during the measurements. Some membrane details imaged with the AFM have also been observed using a scanning electron microscope and their dynamic behavior has been confirmed by microcinematography. We believe that the AFM will offer new insights into the exploration of dynamic changes affecting cell membranes. PMID- 8457679 TI - Influence of chirality on the structure of phospholipid monolayers. PMID- 8457680 TI - SAXS study of crotapotin at low pH. AB - The structure of crotapotin, a protein extracted, from the venom of the Crotalus durissus terrificus, in solution at pH = 1.5, was studied by SAXS. The experimental results yield structural parameter values of the molecular radius of gyration Rg = 13.6 A, volume v = 16.2 x 10(3) A3 A3 and maximal dimension Dmax = 46 A. The distance distribution function deduced from the scattering measurements is consistent with an overall molecular shape of an oblate ellipsoid of revolution with asymmetry parameter v = 0.45. PMID- 8457681 TI - Movement of actin away from the center of reconstituted rabbit myosin filament is slower than in the opposite direction. AB - By decreasing ionic strength slowly, thick filaments of several micrometers in length were obtained from purified rabbit skeletal muscle myosin. Dark-field observation showed these filaments with their center scattering light extensively. Active movement of actin filaments complexed with tetramethyl rhodamine-phalloidin along the reconstituted myosin filaments was observed. Actin filaments moved towards the center of myosin filaments at a speed of 3.9 +/- 1.6 microns s-1 (mean +/- SD, n = 40) and often continued to move beyond the center towards the tip of the opposite side at a lower speed. The speed of the movement away from the center was 1.0 +/- 0.6 microns s-1 (n = 59). Thus, the functional bipolarity in terms of the movement speed which was first found in native thick filaments of molluscan smooth muscle is also seen in reconstituted filaments from purified rabbit skeletal muscle myosin. The difference of the speed between the two directions is considered to be due to properties of myosin molecules themselves. PMID- 8457682 TI - Quality assurance of medical research? PMID- 8457683 TI - Major differences in trauma care between hospitals in Sweden: a preliminary report. AB - The quality of trauma care has been studied at five different Swedish hospitals. The results suggest that improvements in the quality of medical care for patients with severe road traffic injuries can be achieved by reorganizing the highly decentralized trauma care system in Sweden. Above all there is a need for a better structure and organization of the on-call system and of the cooperation of physicians of different specialties within the hospital. The medical care of patients with severe injuries was delayed in 30% and was inappropriate in 7% of cases. Assessment of the quality showed great variation between the hospitals. The medical care was in fact not best at the university hospital but at one well functioning small hospital. It was an effect of an on-call system at the small hospital, which guarantees rapid participation of senior staff in both general surgery and orthopaedic surgery. The greatest problems arose in early diagnosis and treatment of bleeding in abdominal injuries. This was caused by inexperience in the first on-call team in combination with late assessment by second on-call consultants. Fractures of the femoral shaft in almost half of the cases did not get definitive surgery until several days after the accident. PMID- 8457684 TI - Patient satisfaction surveys subsequent to hospital care: problems of sampling, non-response and other losses. AB - Patient questionnaires are commonly used to assess patient satisfaction. This study reports on methodological experiences based on practical use of a Swedish questionnaire. The material consists of questionnaires from five different studies at some 60 wards in three hospitals. Four of the studies were performed by "routine procedure", while one was performed specially to study sampling, non response and other losses. The results showed that a large number of patients were not given a questionnaire despite the fact that they should have been included according to the sampling criteria. In the special study barely half of those discharged answered a questionnaire corresponding to only about one in four in some studies performed routinely. Many of the patients excluded were probably in a difficult situation and their needs ought to be particularly noticed. This was true of patients who were old or confused, had language difficulties, were seriously ill, or who died during the care episode. PMID- 8457685 TI - Do doctors need Deming? PMID- 8457686 TI - Quality comparisons between privately and publicly managed health care centres in a suburban area of Stockholm, Sweden. AB - As in many other countries, the health care system in Sweden is currently undergoing rapid changes. Within a framework of public financing, the delivery of health care is to an increasing extent being transferred to various entrepreneurs; private, public or cooperatives. A privately run, but publicly financed, health care centre was evaluated with regard to quality and costs. Quality was defined in terms of the central guidelines for Swedish primary health care: first level responsibility, accessibility, a holistic view of the patient, and continuity of care and safety. The services offered by the private health care centre were evaluated by different methods--questionnaires, health care utilization data and economic analyses--and found to be of similar quality but produced at a lower cost than by three publicly managed health care centres. PMID- 8457687 TI - What is important in psychiatric inpatient care? Quality of care from the patient's perspective. AB - The development of quality assurance programs for psychiatric care has increased the interest in quality of care and accountability from the patient's perspective. However, most investigations of patient satisfaction use instruments which rate aspects of care defined and held to be important by professionals and care givers. The aims of this study were 2-fold. To map descriptive characteristics of ideal inpatient psychiatric care through open patient interviews, using a sample of 78 hospitalized patients and, secondly, based on a content analysis of these interviews, to have another sample of 77 hospitalized patients rank the importance of 48 treatment characteristics extracted from the qualitative analysis. Results of the content analysis showed that characteristics of ideal inpatient treatment could be classified in six categories: staff-patient relationship, patient co-influence, treatment content, activities, ward atmosphere and staff competence. Results from the patients' rating of the importance of treatment characteristics showed that patients put the highest emphasis on staff empathic qualities: being caring, interested and understanding, respecting patients, devoting time to patients, and creating a safe treatment environment. The least importance was ascribed to characteristics of the physical environment and daily routines on the ward. It is concluded that in order to secure content validity of investigations of the quality of psychiatric inpatient care from the patient's perspective, effort should be put into including the areas of staff-patient relationships and patient information and co-influence. PMID- 8457688 TI - The appropriateness of human albumin use in the hospital of Padova, Italy. AB - The authors present the findings of a study in three stages (1989-1991) on the appropriateness of human albumin use at the hospital of Padova, Italy. In the first stage, guidelines for appropriate use were defined and a monitoring system was set up. In the second stage, compliance of the hospital departments with the new guidelines was assessed in a sample of human albumin prescription charts and related medical records. This revealed a reduction in consumption of 25%. Sixty eight per cent of all albumin was given for indications that are only occasionally appropriate. The information given in the prescription chart agreed with the diagnosis contained in the medical records in 78% of cases. At the end of this stage new regulating mechanisms were introduced. The third stage consisted of a medium-term assessment and produced basically the same results as the previous stage. Crucial steps in the implementation of effective actions in quality improvement processes have been discussed. PMID- 8457689 TI - Quality nursing care survey, 1988-1990. AB - In a quality nursing care survey conducted in Israel, 1988-1990, the four nursing process components were examined. The survey covered 13 hospitals with 119 medical and surgical wards, in which the nursing care quality for a sample of 2065 patients was assessed. Instruments used were (a) the Patient Classification Form, to assess patient dependency level, and (b) Monitor--an index of the quality of nursing care for acute medical and surgical wards [Goldstone et al., Polytechnic Products, Newcastle upon Tyne, 1982], a British adaptation of the Rush Medicus methodology [Jelinek et al., US Dept of Health, Education and Welfare, 1974]. The survey process involved orientation of the hospitals' senior staff, and training of participants in the administration of patient classification and of Monitor. The highest quality nursing care was found in "Meeting the patient's physical needs"; the lowest in "Assessment and planning of patient care". Factors chosen for possible influence on quality of nursing care were: patient dependency category, type of ward (medical, surgical), ward size and hospital size. The most influential factor was found to be the patient dependency category. PMID- 8457692 TI - The agreed indications and contra-indications for cholecystectomy. AB - Indications as to which patients should undergo cholecystectomy remain, at least in part, a matter of controversy. In 1987, a panel of nine Israeli physicians from different specialties established a list of indications for the performance of cholecystectomy based on the literature available at the time. The panel agreed that cholecystectomy was appropriate for 59 indications and that it was inappropriate for 58. The major indications for surgery were biliary colic and acute cholecystitis. Patients who were asymptomatic or had vague symptoms were not recommended to undergo surgery unless they had stones in the common bile duct and were less than 71 years of age. Patients with pancreatitis were recommended for surgery if they had stones in the common bile duct and did not have a history of alcohol abuse. Performing a cholecystectomy at the same time as abdominal surgery was being performed for other reasons was indicated only if the patient was symptomatic from his gall-stones. PMID- 8457691 TI - Indications for cholecystectomy: the results of a consensus panel approach. AB - A consensus panel approach was used in Israel to develop a list of clinical indications for which there was agreement that cholecystectomy should be performed. Nine physicians from different disciplines were asked to score a list of 266 clinical indications for cholecystectomy. Each indication was scored on a scale of 1 (inappropriate, i.e. health risks exceed health benefits) to 9 (appropriate, i.e. benefits exceed risks). Each indication also included one of four comorbidity levels (none to high). Agreement and disagreement were defined and panelists met to discuss, modify and rescore the list. The composition of the panel and definitions of agreement had a considerable impact on the preparation of a list of agreed, appropriate indications for cholecystectomy. Gastroenterologists in the panel were less likely to recommend surgery than either surgeons or general internists both before and after the panel discussion. Following the discussion the level of agreement (defined as after discarding the highest and lowest score all of the remaining seven panelists were in a 3-point range) increased from 39% to 46% (p < 0.08) and disagreement decreased from 27% to 18% (p < 0.01). Fifty-nine of the 266 indications were considered appropriate with agreement. PMID- 8457690 TI - An instrument to assess acute respiratory infection case management in Egypt. AB - To develop an instrument to measure the quality of acute respiratory infection (ARI) case management among Egyptian children. METHODS: A baseline survey of all health facilities in a single district, using a multi-data source instrument. Data sources included providers, caretakers, patient records and observation of patient care. MAIN RESULTS: Physicians did not count the respiratory rate and check for subcostal retraction. Eighty-seven per cent of children who did not require antibiotics received them. Of five children who required antibiotics, four (80%) were prescribed an oral regimen. Three of these should have been admitted to a hospital but were not. Antibiotics were available at the facilities an estimated 7.9 months per year. Oxygen for inpatient treatment was available in one of two hospitals. CONCLUSIONS: This instrument was useful for comprehensively evaluating facility capability to provide quality case management. Deficiencies were identified but were not unexpected in a baseline survey. The Egypt ARI program has the potential to have a substantial impact on how children with ARI are diagnosed and treated in health facilities. PMID- 8457693 TI - Effect of total hip replacement on quality of life. PMID- 8457694 TI - [Drug dependence]. PMID- 8457695 TI - [Challenges to nursing personnel and their education]. AB - Challenges for developing nurses as persons and personalities during their education are being described in the article. The major thesis is that thorough understanding of the mission of nursing is the ground from which all educational goals derive their origin. In nursing education a reformed relationship between the teacher and the student is needed which facilitates balanced development of ethical, empirical, esthetic and personal knowledge of the student. In this way the future nurse may grow a thinker and an active risk-taking actor who bases her solutions on good knowledge base and moral reasoning. Understanding of the meaning of history, culture and international collaboration are also necessary in the development of versatile personalities. PMID- 8457697 TI - Has your organization begun to shift the "quality paradigm"? PMID- 8457696 TI - [Nursing activities and addictive drugs--what nurses should know and understand]. AB - This article describes the identification of intoxicant addiction and help given to those clients having this kind of a problem. Nursing care of these clients demands expert knowledge everywhere in healthcare sector. Observation and communication skills are stressed being as important as knowledge. Basic nursing care skills are also needed. PMID- 8457698 TI - A new architecture for quality assurance: nurse-physician collaboration. PMID- 8457699 TI - From unit-based quality assurance to multidisciplinary continuous quality improvement in the coronary care unit. PMID- 8457700 TI - A continuous quality improvement approach to medication administration. PMID- 8457701 TI - Prenatal quality of life outcomes for a public health quality assurance system. PMID- 8457702 TI - Improving care for the patient with epilepsy. PMID- 8457703 TI - Defining quality services in a general pediatric unit. PMID- 8457704 TI - Improving outcomes for patients experiencing alcohol withdrawal. PMID- 8457705 TI - An outcome evaluation of a six-week childbirth education class. PMID- 8457706 TI - Quality assurance and quality improvement programs. PMID- 8457707 TI - In what ways can we reward employees as a part of our quality program? PMID- 8457708 TI - Operationalizing collaborative quality assurance: the 7 Gryzmish experience. PMID- 8457709 TI - In vitro evaluation of the antineoplastic activity of combretastatin A-4, a natural product from Combretum caffrum (arid shrub). AB - Combretastatin A-4 is a natural product which was isolated from the South African tree Combretum caffrum. In this study, the cytotoxic activity of combretastatin A 4 was tested in radiometric and human tumor cloning assays against eight different tumor cell lines and against 15 patient tumors in the human tumor cloning assay. To test the preferential cytotoxicity of combretastatin A-4 against tumor cells versus non-tumor cells, it was also tested in the radiometric assay against both normal human diploid fibroblasts and human bone marrow cells. Of the eight cell lines used, combretastatin A-4 showed preferential cytotoxicity for six of them. In addition, combretastatin A-4 showed a concentration-dependent cytotoxicity against a variety of human tumors. Based on the data generated in this study, combretastatin A-4 should be further tested in in vivo preclinical models. PMID- 8457711 TI - Flavone acetic acid--from laboratory to clinic and back. AB - Flavone acetic acid ester (NSC 293015, LM 985) emerged from a series of flavonoids from Lyonnaise Industrielle Pharmaceutique (Lipha) screened by the National Cancer Institute. LM 985 showed modest but sufficient activity in the P388 pre-screen to progress to secondary evaluation on the solid colon 38, where significant activity was seen. On the basis of this particular profile LM 985 was selected by the Cancer Research Campaign (CRC) UK for phase I clinical trial. It was not recommended for phase II trial because of drug associated hypotension and the fact that it appeared to act as a pro-drug for flavone acetic acid (NSC 347512, LM 975, FAA) which was shown to be responsible for the dramatic solid tumor activity in mice. This was manifested as dramatic hemorrhage necrosis and involves a complex mechanism of action. FAA proceeded to clinical trial but unfortunately no anti-tumor activity was seen. A large amount of effort has been channelled into identifying the mechanisms of action of FAA in mice and it is clear that activity relies on a number of factors. Subcutaneous tumors respond dramatically whereas ascites tumors and tumor deposits in other sites are usually less responsive. Establishment of a tumor blood vasculature system appears necessary for response and adequate drug concentrations within a therapeutic window are necessary. From the large body of information available at present the most likely explanation for discrepancies in activity between mouse and man seems to relate to differences in the ability of the immune system to respond to FAA, although variation in the composition of the vasculature cannot yet be ruled out. Analogs of this type of compound are worth pursuing but it is necessary to examine them in appropriate model systems in order to predict for possible clinical activity. PMID- 8457710 TI - Selective delivery of etoposide to intraperitoneal tissues using a new dosage format: etoposide microcrystals suspended in oil. AB - Rats received an intraperitoneal bolus injection of etoposide at 5 mg/kg of body weight in the form of an etoposide microcrystal suspension in oil (ETOP-OIL) or an aqueous etoposide solution. The tissue distribution was subsequently analyzed using high performance liquid chromatography. ETOP-OIL delivered significantly greater amounts of etoposide and for a longer duration to the intraperitoneal tissues such as the omentum and the spleen, whereas it delivered significantly less etoposide to the rest of the body such as the lung, the heart and the bone marrow, than the aqueous etoposide solution. PMID- 8457712 TI - Phase II study of 13-cis-retinoic acid and interferon-alpha 2a in patients with advanced squamous cell lung cancer. AB - The combination of interferon (IFN)-alpha 2a and 13-cis-retinoic acid (13-cRA) has demonstrated significant antitumor activity in patients with advanced squamous cell cancer of the skin and cervix. We performed a prospective phase II trial of this combination in patients with locally advanced or metastatic squamous cell lung cancer. Twenty-one patients were enrolled on the study. All patients were evaluable for toxicity and 17 were evaluable for response, four with locally advanced and 13 with metastatic disease. One partial response was obtained in a patient with locally advanced disease. Toxicity consisted mainly of constitutional side effects (fatigue, anorexia), which resulted in eight patients coming off-study. The combination of IFN-alpha 2a and 13-cRA is unlikely to exhibit significant clinical activity in patients with metastatic squamous cell lung cancer, but activity in patients with locally advanced disease has not been excluded. PMID- 8457713 TI - Removal of the basic center from doxorubicin partially overcomes multidrug resistance and decreases cardiotoxicity. AB - Hydroxyrubicin, a synthetic doxorubicin analog in which the basic amino group at C-3' is replaced by a hydroxyl group, was used as a prototype compound to study the effects of basicity of the sugar moiety on the toxicity and antitumor activity of anthracycline antibiotics. Compared with doxorubicin, hydroxyrubicin showed similar or superior in vitro cytotoxicity against P388, L1210, and M5076 cells, as determined by an MTT assay, and against 8226 and CEM cells, as determined by a growth inhibition assay. Hydroxyrubicin was 5 and 13 times more effective than doxorubicin in inhibiting the growth of multidrug-resistant CEM (CEMvbl) and 8226 (8226R) cells, respectively. Hydroxyrubicin was not cross resistant with doxorubicin in a cytotoxicity assay against KB 3-1 and KB V1 cells (resistance index 1.1 for hydroxyrubicin versus > 15.6 for doxorubicin). Cellular uptake and retention of hydroxyrubicin were studied by flow cytometry in parent and multidrug-resistant 8226 cells, and compared with those of doxorubicin. In 8226 sensitive cells, 2 h uptake and retention of doxorubicin were similar or higher than those of hydroxyrubicin. In 8226R cells, uptake and retention of hydroxyrubicin were about 3-fold higher than those of doxorubicin. In mice, the acute LD50 of hydroxyrubicin was about 3-fold higher than that of doxorubicin (79.1 versus 25.7 mg/kg). At equitoxic doses, hydroxyrubicin was as myelosuppressive as doxorubicin but less cardiotoxic, as assessed by the Bertazzoli test. In contrast to doxorubicin, hydroxyrubicin, due to the lack of basic amine function, showed no selective interaction with negatively-charged cardiolipin (CL). The observed decrease of affinity to CL might be responsible for the reduced cardiotoxicity of hydroxyrubicin. In in vivo antitumor activity studies, hydroxyrubicin at the optimal dose (37.5 mg/kg, i.p., on day 1) had significant activity against intraperitoneal P388 leukemia resistant to doxorubicin, whereas doxorubicin (10 mg/kg, i.p., on day 1) was inactive (%T/C 163-200 versus 118-120). These studies indicate that: (i) the amino group at position 3' is not essential for doxorubicin to exert its biological activity, (ii) removal of the basic center (deamination at the C-3') results in an increased cellular uptake and retention, (iii) the increased cellular uptake and retention of hydroxyrubicin in multidrug-resistant cells correlate with a partial or total lack of cross-resistance of this analog with the parent compound, doxorubicin, and (iv) deamination at position 3' confers a reduced cardiotoxicity and diminished affinity for CL. PMID- 8457714 TI - Phase II trial of amonafide in advanced colorectal cancer: a SouthWest Oncology Group study. AB - Amonafide is a substituted benzisoquinolinedione that exerts its cytotoxicity through effects on macromolecular synthesis and intercalation of DNA. In this trial, 44 patients with advanced colorectal cancer and without prior chemotherapy received amonafide at a starting dose of 300 mg/m2 intravenously over one hour, on a daily x 5 schedule every 3 weeks. Toxicities of grade 3 or above included granulocytopenia, thrombocytopenia, sepsis, anaphylaxis and transient aphasia. Forty-seven % of patients had grade 3 or higher toxicity of any type. There were no complete or partial responses for an overall response rate of 0%, with a 95% confidence interval of 0-9%. The level of toxicity observed on this trial suggests an appropriate dose intensity of amonafide, despite lack of knowledge of patients' acetylator phenotypes. PMID- 8457715 TI - A phase I study of lobaplatin (D-19466) administered by 72 h continuous infusion. AB - A phase I trial with continuous intravenous infusion of lobaplatin (D-19466; 1,2 diamminomethyl-cyclobutane-platinum (II)-lactate) for 72 h was performed to determine the maximum tolerated dose (MTD). Each patient received a single dose level, the total dose of lobaplatin ranged from 30 to 60 mg/m2/72 h every 4 weeks. Eleven patients enroled in this study and received a total of 30 courses of lobaplatin (median 2; range 1-6). Thrombocytopenia was the dose-limiting toxicity, it reached WHO grade III in three out of six patients at 45 mg/m2/72 h, and WHO grade IV in two out of two patients at 60 mg/m2/72 h. Leucocytopenia was mild, as was nausea and vomiting. Phlebitis at the infusion site was found in three patients. During this trial there were no signs of renal, neuro- or ototoxicity. One patient with ovarian cancer, pretreated with three different platinum complexes, achieved a partial response now lasting for longer than 6 months. In conclusion, thrombocytopenia is the dose-limiting toxicity of lobaplatin administered by 72 h continuous infusion. The recommended phase II dose for this regimen is 45 mg/m2/72 h every 4 weeks. PMID- 8457716 TI - Antineoplastic activity in vitro of free and liposomal alkylphosphocholines. AB - We investigated the liposome forming properties of three homologues of alkylphosphocholines: hexadecylphosphocholine (HPC), octadecylphosphocholine (OPC) and eicosanylphosphocholine (EPC). In the presence of cholesterol and dicetylphosphate, alkylphosphocholines form liposomes with slow permeability for entrapped carboxyfluorescein. We studied the direct cytotoxicity of alkylphosphocholine vesicles and their ability to attack MethA sarcoma cells, human skin and muscle fibroblasts (M22, GUS, Moscow), and human mouth epidermoid carcinoma cells (KB, ATCC, CCL 17). All alkylphosphocholines show cytotoxic activity against the investigated cells, the degree of which depends on the number of carbon atoms in the alkyl chain, concentration and incubation time. Whereas the etherlipid liposomes are less toxic to MethA cells than the free compounds, the liposomal alkylphosphocholines are more toxic toward KB and M22 cells than the corresponding free lipids. PMID- 8457717 TI - Targeting of GM2-bearing tumor cells with the cytolytic Clostridium perfringens delta toxin. AB - The cytolytic Clostridium perfringens delta toxin lyses selectively cells which express ganglioside GM2. In this study, we investigated whether delta toxin can be used to characterize GM2 on tumor cell membranes and as an antitumor agent. The sensitivity to lysis by delta toxin of various murine and human malignant cell lines and also normal tissues was quantified using a 51Cr-release assay. The cytotoxicity titers were correlated with the 125I-labeled toxin binding capacity of sensitive and insensitive cells. Seven of eight human melanomas tested were lysed by the toxin and, of these, four were very sensitive (cytotoxicity titers below 12 ng of toxin). All neuroblastomas, gliomas and the retinoblastoma tested were lysed with 3-18 ng of toxin. Three of six carcinomas and one of two sarcomas were also very sensitive (cytotoxicity titers 0.6-15 ng) whereas leukemias and lymphoma cells were insensitive. Normal human tissues were insensitive (erythrocytes, skin fibroblasts) or poorly sensitive (brain, lung, spleen). The in vivo antitumor activity of delta toxin was tested in tumor-bearing mice. Daily intra-tumor injections of 0.5-1 mg of toxin for 4-5 days in carcinoma Me180- and melanoma A375-bearing nude mice, and neuroblastoma C1300-bearing A/J mice significantly inhibited tumor growth for 12-36 days. Intravenous administration of 100 ng of toxin per day for 5 days in Me180-bearing nude mice and C1300 bearing A/J mice gave significant inhibition of tumor growth only during the treatment period, and 10 injections of the same dose of toxin had no significant effect on SK-MEL28, a tumor lacking GM2. PMID- 8457718 TI - Differential interaction of cisplatin with the HIV-1 long terminal repeat in a resistant ovarian carcinoma cell line. AB - We constructed a recombinant plasmid, pBHIV1, carrying the long terminal repeat (LTR) sequences of HIV-1 linked to the reporter chloramphenicol acetyl transferase (CAT) gene and to the aminoglycoside phosphotransferase (aph) gene as a selectable marker. We have introduced pBHIV1 in a human ovarian cancer cell line A2780 and in a cisplatin resistant variant 2780CP, and obtained stable geneticin resistant A27HIV1-1 and 27CPHIV1-1 cells, respectively. Both transfectant cells expressed CAT activity from the HIV LTR promoter. The response to the anti-neoplastic drug cisplatin was studied on the LTR regulated CAT activity in both cell lines. It was found that cisplatin at 2.5 x 10(-5) M concentration stimulates the expression of CAT by 26-fold from the HIV LTR in A27HIV1-1, but requires a concentration of 5 x 10(-5) M to enhance expression by 4.1-fold in the cisplatin resistant 27CPHIV1-1 cells. Carboplatin, over a range of concentrations (1 x 10(-6) to 1 x 10(-4) M), does not stimulate expression of CAT from the HIV-1 LTR in either of the transfected cells. PMID- 8457719 TI - Comparative nephrotoxicity of carboplatin and cisplatin in euvolemic and dehydrated rats. AB - The aim of this study was to compare the renal tolerance of cisplatin and carboplatin in euvolemic and dehydrated rats. A total of 79 euvolemic or dehydrated male rats were randomly assigned to receive cisplatin (5 mg/kg body weight, i.p.), carboplatin (40 mg/kg body weight, i.p.) or vehicle. Body weight, serum creatinine, creatinine clearance, fractional excretion of sodium and urinary NAG excretion were recorded on days 1 and 5. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and renal histology were determined on day 5. In the euvolemic and dehydrated control and carboplatin groups we observed no change in serum electrolytes, serum creatinine, creatinine clearance, GFR and ERPF. In the euvolemic and dehydrated control groups we observed no change in urinary NAG excretion. Carboplatin induced a slight but significant increase in urinary NAG excretion. In dehydrated rats carboplatin induced a significantly higher increase in urinary NAG excretion than in euvolemic rats. Cisplatin induced a marked and significant decrease in GFR and ERPF, and a significant increase in NAG. Dehydration markedly potentiated cisplatin nephrotoxicity. Euvolemic rats treated with cisplatin exhibited slight renal lesions with a mean score which was similar to the control group. The most extensive lesions were observed in euvolemic and dehydrated cisplatin treated rats with tubular necrosis in the outer stripe of the medulla.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457720 TI - Ascorbic acid-enhanced antiproliferative effect of flavonoids on squamous cell carcinoma in vitro. AB - We examined the effects of flavone and two polyhydroxylated plant flavonoids (quercetin and fisetin), either singly or in combination with ascorbic acid, on the growth of a human squamous cell carcinoma cell line (HTB 43) in vitro. Fisetin and quercetin significantly impaired cell growth in the presence of ascorbic acid. Exposure of cells to ascorbic acid (2 micrograms/ml) and 2 micrograms/ml of either fisetin or quercetin resulted in 61 and 45% inhibition of cell growth, respectively, in 72 h, while treatment with ascorbic acid alone had no effect on cellular proliferation. Flavone and ascorbic acid, either as single agents or in combination, exhibited no significant inhibition at any of the concentrations tested. The enhancement of the antiproliferative effect of the above flavonoids by ascorbic acid may be due to its ability to protect these compounds against oxidative degradation. PMID- 8457721 TI - Autologous cysteine peptidase inhibitors as potential anticancer drugs. PMID- 8457722 TI - Matrix-assisted laser desorption time-of-flight mass spectrometry of oligonucleotides using 3-hydroxypicolinic acid as an ultraviolet-sensitive matrix. AB - Matrix-assisted laser desorption time-of-flight mass spectrometry has been used to produce quasi-molecular ion signals from underivatized mixed-base single stranded DNA oligomers ranging from 10 to 67 nucleotides in length. These results were obtained with a new matrix material, 3-hydroxypicolinic acid (3 hydroxypyridine-2-carboxylic acid) which showed significant improvement over many previously reported matrices studied in terms of mass range available, signal-to noise ratio, and the ability to analyze mixed-base oligomers. The desorption and simultaneous ionization was by pulsed laser light at 10 to 50 mJ/cm2, studied at 266, 308, and 355 nm. Spectra taken at 266 nm provided the smallest amounts of doubly charged and dimer ions--characteristics desirable for DNA sequencing by this technology. Negative-ion spectra were uniformly superior to positive-ion spectra. This new matrix also is quite effective for molecular weight determinations of peptides and proteins in both positive- and negative-ion modes. PMID- 8457723 TI - Principles of specificity and redundancy underlying the organization of the olfactory system. PMID- 8457724 TI - Glial cells in the nerve fiber layer of the main olfactory bulb of embryonic and adult mammals. AB - This article provides a detailed description of the glial cell types in the nerve fiber layer of the main olfactory bulb during embryonic development, in adult mammals, and at the nerve entry zone of the first cranial nerve. In adult mammals, the glial cell types of the olfactory nerve fiber layer include intrafascicular ensheathing cells, which have the exclusive role of ensheathing the olfactory axons in both the PNS and CNS, and interfascicular astrocytes, which occupy the spaces between adjacent olfactory fascicles. The ensheathing cells are particularly interesting because they possess a mixture of Schwann cell and astrocytic phenotypic features, are more likely to be of placodal than of CNS origin, and have the exclusive role of forming the glia limitans at the PNS-CNS transitional zone. It is proposed that one important function of ensheathing cells is to modulate the growth of olfactory axons within the CNS; this modulation is probably mediated by selective cell adhesion molecules, extracellular matrix molecules, and chemotropic agents. PMID- 8457725 TI - Molecular and cellular properties of mammalian primary olfactory axons. AB - How are the axonal projections of olfactory and vomeronasal receptor neurons to the olfactory bulb formed during development? How are the primary olfactory axonal connections functionally organized? With progress in molecular biological techniques and histochemical methods, it became possible to study cellular strategies and molecular mechanisms which guide the primary olfactory axons of the main and accessory olfactory systems to the target glomeruli in the bulb. In addition, new methodologies have begun to elucidate various subsets of the primary olfactory axons with distinctive central connections. The aim of the present paper is to review (1) the characteristic organization of the projection of the primary olfactory axons, (2) projection patterns of histochemically defined subsets of primary olfactory axons, and (3) information on molecules expressed by the surface membrane of the primary olfactory axons. This knowledge gives insight into the functional organization of the primary olfactory axon projection, which is indispensable for understanding signal processing in the olfactory system. This knowledge also underscores the notion that the primary olfactory axon projection provides an excellent model system in which to study axonal guidance and the formation of specific synaptic connections. PMID- 8457726 TI - Functional organization of the main olfactory bulb. AB - Complete understanding of the role of the mammalian main olfactory bulb in sensory processing has remained elusive despite many detailed studies on its anatomy and physiology. Several lines of recent evidence viewed in the context of earlier knowledge have provided new insights into the bulbar mechanisms of olfactory coding. The output cells of the olfactory bulb receive a localized olfactory nerve input and interneuronal input via dendrodendritic synapses on distinct sets of dendrites. The spatial arrangement of granule cell contacts on output cell basal dendrites suggests that lateral inhibitory interactions may occur between neighboring output cells. The input from olfactory receptor cell axons to the bulb also has spatial order, but does not represent a precise map of the receptor surface. Recent studies with antibodies and lectins suggest that different groups of axons from chemically similar receptor cells collect into certain glomeruli, even if the axons originate from cells that are not contiguous in the mucosa. Electrophysiological studies have begun to explore the participation of spatially organized circuits in olfactory processing. The degree to which neighboring output cells respond similarly to odor stimulation, for example, depends on the distance between the cells, with those further apart showing complementary responses. Also, a single output cell can show 2 or more different temporal response patterns when different odors are presented. Intracellular recordings indicate that these responses are shaped by IPSPs. Electrical stimulation during such recordings shows that some mitral cells are excited by nerve inputs close to their glomerular tufts, while they are inhibited by nerve inputs to other parts of the bulb. Finally, recordings from granule and periglomerular cells indicate their potential in mediating components of output cell odor responses. These considerations suggest that the olfactory bulb performs a spatially based analysis on the information coming from the receptor cells. While the spatial organization of the olfactory bulb is probably not faithfully represented in the projections to the olfactory cortex, bulbocortical projections are not random. The fact that spatial factors exist at each of these levels in the olfactory system must be considered in developing models of central olfactory processing. PMID- 8457728 TI - The effect of aluminium coating on elemental signals in X-ray microanalysis. AB - It has been determined that, in the normal range of aluminium coating thicknesses used to remove charge from non-conducting specimens in the electron microscope, no detectable influence on the elemental signals obtained in X-ray microanalysis is observed. This is in contrast to a previous report (Hopkins et al., J. Electron Microsc. Tech., 18:176-182, 1991) of a reduction in elemental signal with increasing aluminium coating thickness. An explanation of errors in the previous interpretation is provided. PMID- 8457727 TI - Are there structural and functional modules in the vertebrate olfactory bulb? AB - A number of different recording methods have shown that odorants elicit patterns of neuronal activity widely distributed across cells of the olfactory receptor epithelium, olfactory bulb, and piriform cortex in the vertebrate olfactory system. These findings suggest that the physicochemical properties of odorant molecules are processed by distributed coding mechanisms activated in parallel in olfactory circuits in order to characterize a single, "monomolecular" odorant. These findings also suggest that the response patterns seen at higher levels are set up by differential responses in peripheral receptor cells of the olfactory epithelium. One requirement for understanding the details of this proposed encoding scheme is correlation of odor-generated patterns with the components of these circuits. In this paper, results from 2-deoxyglucose and voltage-sensitive dye studies suggest that certain components of these responses may relate to patterns established in reproducibly identifiable aggregates of bulbar cells. These findings are consistent with previous observations suggesting that columnar groups of periglomerular, mitral/tufted and granule cells, oriented perpendicular to the laminae of the bulb, are functionally related to one another. Such cell groups or modules, when activated in parallel, could serve as building block components of the complete ensemble response. According to this hypothesis, different sets of such modules would be activated with different odorant stimuli and modules could be shared to the degree to which the physicochemical properties of the different stimuli overlap. PMID- 8457729 TI - Programmable freeze-substitution and cryo-embedding device. AB - The construction and performance of a modular and fully controllable freeze substitution device are described. The core of the device consists of a heavy brass block providing a large, stable thermal mass. The block is composed of two perforated plates and a base plate forming nine deep wells, which enable the concomitant substitution of several samples in various substitution fluids, and in large volumes. The wells are surrounded by an isometric network of tunnels through which either liquid nitrogen or hot air can flow. The isometric network enables heat transfer across short uniform distances throughout the entire block's volume, thus minimizing temperature gradients and differences. The temperature of the substitution fluid, rather than that of the metal block, is monitored by a programmable controller, enabling the presetting of any freeze substitution regime. PMID- 8457730 TI - Improved TEM samples of semiconductors prepared by a small-angle cleavage technique. AB - A small-angle cleavage technique has been developed that produces superior transmission electron microscope (TEM) samples of semiconductors and related materials. The technique involves back-thinning the sample to approximately 100 microns, then scribing a groove on this back face at a specified small angle to a standard cleavage plane. The sample is cleaved along this scribe line followed by cleaving along the standard cleavage plane to produce a thin wedged sample. Samples prepared by this method are characterized and compared with conventional and low-angle ion milled samples. The technique is illustrated, and the characteristic geometry of the cleaved sample is explained in terms of a simplified cleavage model. PMID- 8457731 TI - Simulation of dislocations imaged by moire fringe contrast. AB - Transmission electron microscope (TEM) images of dislocations as produced via moire fringe contrast are simulated using many-beam diffraction theory. The effect of edge dislocations on both parallel and rotational moire fringe patterns is considered. For the parallel moire fringe pattern, images of dislocations both perpendicular to the film plane and those inclined to the film plane are produced. The effect of an inclined dislocation is shown to cause a distortion of the dislocation image. Finally, a comparison between predicted and experimentally observed images is made, with the results indicating that threading dislocations in the FeAl/GaAs system have line directions nearly perpendicular to the (001)FeAl/GaAs film plane. PMID- 8457732 TI - Application of Markov chains to linked genes with interference. II. Genotypic selection. AB - The case of a selfing population and three diallelic loci under genotypic selection is considered. Expressions are obtained for the mean number of times that a process passes through a transient state, for the mean number of generations needed to reach an absorbing state, and for other interesting parameters. The variates under analysis are the coefficient of coincidence, the probabilities of recombination, and the genotypic fitness. The expressions obtained allow the direct computation of the entries of the inverse matrices, avoiding the inverting routines that could present problems of ill-conditioning. Three types of inheritance for fitness are considered in a numerical application: no dominance, complete dominance, and overdominance. Finally, the possible existence of interaction between coincidence and dominance for fitness is analyzed. PMID- 8457733 TI - The effect of age-dependent host mortality on the dynamics of an endemic disease. AB - Using asymptotic expansions in the ratio between the duration of infection and host lifetime, equilibrium conditions are analyzed for an SIR-type epidemic model with age-dependent mortality and age-independent disease transmission. Disease incidence at equilibrium depends on the distribution of lifetimes. Incidence is maximal if host life span is fixed and, for vanishing higher moments, it decreases with increasing variance of the distribution. The spectrum of the linearization about the endemic equilibrium has two dominant components, one near 0 and one with a large imaginary part. All roots of the characteristic equation have a negative real part so the model is always stable. The roots with a large imaginary part dominate in most cases, indicating that the approach to equilibrium will be through slowly damped oscillations. PMID- 8457734 TI - Relationship between compartmental masses and transition rates in stochastic compartmental models. AB - A class of stochastic linear compartmental models are studied for which the mean (average) compartmental masses satisfy a linear system of ordinary differential equations. Solutions of the system for mean masses and solutions of the compartmental model with mean compartmental matrix are compared. Certain examples demonstrate the usefulness and applicability of the considered class of stochastic compartmental models. PMID- 8457735 TI - Better resuscitation training needed. PMID- 8457736 TI - Nurses face a fragmented health service in 1993. PMID- 8457737 TI - Hip replacement in the elderly. AB - Hip replacement is commonplace and generally successful except for the very elderly in whom repeated surgery may be necessary. The benefit for many of these patients is questioned in the context of predictability of outcome and consideration of quality of life and death. PMID- 8457738 TI - The effects of malnutrition in hospital. AB - Between 30 and 50% of inpatients suffer some degree of malnutrition and as a result have a higher risk of complications and higher mortality than well nourished patients. Nurses have a fundamental role in combating and preventing malnutrition, yet lack knowledge and understanding of the problem. This article describes the effects of malnutrition and discusses the nurse's role in the provision of nutritional care. PMID- 8457740 TI - Using reflection and experience in nurse education. AB - It has long been recognized that a gap exists between theory and practice in nursing and that the theory learned in the classroom is not seen by students to relate to their area of practice. How can nurse educators narrow this theory- practice gap? This article examines the use of reflection to facilitate cancer nurse education. PMID- 8457739 TI - Caring is the essence of nursing practice. AB - Few would doubt that caring is an integral part of the art and science of nursing. However, unless nurses recognize and promote the value of caring as a basis for rational, scientific practice, their future in healthcare provision may be limited. PMID- 8457741 TI - The shape of things to come. PMID- 8457742 TI - Withdrawing medical treatment: implications of the Bland case. AB - The question of whether it is possible to withdraw a feeding system from a patient who is in a persistent vegetative state raises serious legal and ethical issues which have recently been discussed in the High Court. This article discusses the issues and the Court's conclusions in this particular case. PMID- 8457743 TI - Cardiopulmonary resuscitation: basic life support skills: 1. AB - Basic life support (BLS) is potentially life-saving and unnecessary delays in starting BLS must be avoided. Sudden cardiac death occurs within 1 hour of symptoms in 40% of patients, and in 60% of young/middle-aged patients. BLS can support the casualty and save lives. Bystanders, including nurse aiders, should summon professional help before commencing BLS. Although technical expertise and equipment are necessary in specific situations, BLS 'buys time' while waiting for the equipment to arrive. Seventy per cent of cardiac arrests occur in the home and as BLS skills are often the only skills immediately available, their acquisition is essential. PMID- 8457744 TI - Finance and management. An induction programme for recovery ward nurses. AB - Recovery ward nurses have often been viewed as the poor relations of theatre nurses. However, these nurses need the skills to care for highly dependent patients who have undergone both surgical and anaesthetic procedures. This article describes training for recovery ward nurses at the author's hospital. PMID- 8457746 TI - Anger rises over fallen Prophit. PMID- 8457747 TI - The worm in the APEL (assessment of prior experiential learning) PMID- 8457745 TI - How to be successful when applying for a postregistration course: 2. AB - The process of applying for a postregistration course is complex and the competition for places is great. If a candidate is to be successful he/she must focus on creating a positive impression. This article considers the selection day, tests, group interviews, general performance and the common question that may be asked. PMID- 8457748 TI - Peritoneal dialysis: prescription for the 90s. AB - Over the past decade, continuous ambulatory peritoneal dialysis (CAPD) has been seen as the first-line treatment for patients requiring renal replacement therapy. This article reviews the types of peritoneal dialysis available and describes the advantages of CAPD over haemodialysis. PMID- 8457749 TI - Elder abuse: raising the awareness of nurses working in A & E units. AB - Despite a growing literature, many professionals have a limited knowledge of elder abuse. This article highlights some of the conceptual and practical problems surrounding the topic in order to raise awareness and provide some indication of the nurse's role. PMID- 8457750 TI - Use of humour and laughter in patient care. AB - Research into humour and laughter has indicated that these have psychological, social and physical effects which may have useful applications for patient care. Humour and laughter are potentially useful therapeutic tools but, as yet, little clinical research into their utilization or efficacy has been conducted in the UK. PMID- 8457751 TI - Practice nurses and chronic diseases of the gastrointestinal tract. AB - The potential value of nurse-based counselling of patients with chronic gastrointestinal disorders was investigated through a postal questionnaire survey of practice nurses in Leicestershire. The results suggest there is little prospect of developing practice-based counselling service in gastroenterology. PMID- 8457752 TI - Socialization of student nurses into the qualified nurse role. AB - The journey that a new student nurse makes is a long one during which the traveller undergoes many changes. This article considers the way the student is socialized into the role of qualified nurse. In so doing it explores the part played by the nurse teacher in that process of change. PMID- 8457754 TI - Violent attacks: nurses at risk. PMID- 8457753 TI - Role of ethics in modern health care: 2. AB - The first article in this two-part series examined the meaning of ethics, why nurses should bother with it, and what effect it has on the individual conscience controlled practitioner. This article looks more closely at why nurses need to be aware of the implications of ethics in practice. PMID- 8457755 TI - Nurse-aid management of hypovolaemic shock. AB - Shock is a potentially life-threatening situation and the nurse aider must therefore be able to recognize its development and take immediate action. This article describes the actions that a nurse aider must take at the scene of an accident. PMID- 8457757 TI - Winds of change. PMID- 8457756 TI - Purposeful activity as an indicator of quality in the care of elderly patients. AB - Standards of physical care on continuing care wards have improved but psychosocial care remains generally poor. Purposeful activity is central to the quality of care of patients on respite and continuing care wards and nurses must take greater responsibility for its provision. PMID- 8457758 TI - Overview of lung disease: screening and prevention. AB - The purpose of this article is to review respiratory assessment, common pulmonary diseases, and their risk factors and diagnosis. Prevention and screening are discussed as they relate to chronic obstructive pulmonary disease, asthma including occupational asthma, and interstitial lung disease. PMID- 8457759 TI - Outpatient management of common problems in patients with chronic obstructive pulmonary disease. AB - Dyspnea, ineffective secretion clearance, and the potential for exacerbation are three common problems of patients with chronic obstructive pulmonary disease. Assessment and management of these problems are important in the overall care of this population. Teaching patients breathing exercises and secretion clearance techniques and referring them to comprehensive pulmonary rehabilitation programs improves functional capacity and quality of life. PMID- 8457760 TI - Linda Ebright: pulmonary researcher. Interview by Karna Bramble. PMID- 8457761 TI - Assessment and management of adults with asthma: guidelines for nurse practitioners. AB - Asthma is a potentially life-threatening chronic disease requiring consistent and careful management. NPs play a prominent role in diagnosing, managing, and teaching people with asthma. Understanding current theories of pathogenesis, principals of therapeutic management, and patient education is critical to reduce rising asthma morbidity and mortality. When the patient, family members, and the clinician work together in partnership, an optimal individualized treatment plan can be established. PMID- 8457762 TI - Tuberculosis in the 1990s. AB - Tuberculosis is a disease of major public health significance in the United States. In spite of the existence of drugs for prevention and treatment, the incidence of tuberculosis is on the rise in the United States, particularly among certain high-risk groups. Primary care practitioners must be alerted to the increased incidence and changing epidemiology of tuberculosis and become skilled in methods of detection, prevention, and treatment. PMID- 8457764 TI - Legal liabilities in treating patients with breast cancer. PMID- 8457763 TI - Nicotine dependency treatment: a role for the nurse practitioner. AB - Most patients who continue to smoke are nicotine dependent. By developing a standard procedure for identifying patients who smoke, encouraging cessation on each visit, teaching relapse prevention skills, and following up, NPs can help ease the withdrawal symptoms that accompany the cessation process. Methods that combine the proper use of pharmacological therapy (in the form of nicotine replacement) and behavioral counseling are most effective. PMID- 8457765 TI - Managing prednisone in clients with chronic obstructive pulmonary disease. AB - Prednisone improves airflow in selected individuals with chronic obstructive pulmonary disease. Because of the nature of its adverse effects and because not all clients benefit, the first step in management is giving clients a steroid trial. The decision to continue therapy is based on subjective improvement and objective improvement shown by pulmonary function tests. If therapy is continued, caregivers must find a maintenance dose so that clients receive benefit with less risk of adverse effects. PMID- 8457766 TI - Prescribing supplemental oxygen. AB - Oxygen is a pharmacological agent and requires prescribing by appropriate indications. Indications differ between the patient in an unsteady medical state and one in a chronic hypoxic state. Reimbursement issues must always be a consideration when prescribing, as well as the method of delivery of oxygen. Alternative delivery systems are currently available. The NP must provide proper assessment, education, and follow up evaluations of the effectiveness of the medication. PMID- 8457767 TI - Optimizing the use of metered-dose inhalers in chronic obstructive pulmonary disease and asthma. AB - The metered-dose inhaler (MDI) is a miracle of modern technology, but its use can be burdened with problems. Although it is a small, multidose, portable, safe, efficient, and cost-effective way to deliver inhaled medications, a majority of patients do not use the MDI correctly. The inability to coordinate actuation with inhalation and poor compliance, with both over- and under-use, are the most common problems. Understanding and dealing with the barriers to effective MDI use are essential to optimal care of patients with obstructive airways disease. PMID- 8457768 TI - Primary pulmonary care of the patient with cystic fibrosis. AB - This article presents an overview of the pathophysiology, presentation, diagnosis, current therapy, and promising new research of cystic fibrosis. Focus is on the care of the cystic fibrosis patient by the community primary care provider and coordination of care between primary care providers and Cystic Fibrosis Foundation Centers. PMID- 8457769 TI - A closer look at therapy for chronic asthma. PMID- 8457770 TI - Posttranslational processing of proenkephalins and chromogranins/secretogranins. AB - Posttranslational processing of peptide-precursors is nowadays believed to play an important role in the functioning of neurons and endocrine cells. Both proenkephalins and chromogranins/secretogranins are considered as precursor molecules in these tissues, resulting in posttranslationally formed degradation products with potential biological activities. Among the proteins and peptides of neuronal and endocrine secretory granules, the enkephalins and enkephalin containing peptides have been most extensively studied. The characterization of the post-translationally formed degradation products of the proenkephalins have enabled the understanding of their processing pathway. Chromogranins/secretogranins represent a group of acidic glycoproteins, contained within hormone storage granules. The biochemistry, biogenesis and molecular properties of these proteins have already been studied for 25 years. The chromogranins/secretogranins have a widespread distribution throughout the neuroendocrine system, the adrenal medullary chromaffin granules being the major source of these storage components. Recent data provide evidence for a precursor role for all members of the chromogranins/secretogranins family although also several other functions have been proposed. In this review, some of the methods applied to study proteolytic processing are described. In addition, the posttranslational processing of chromogranins/secretogranins and proenkephalins, especially the biochemical aspects, will be discussed and compared. Recent exciting developments on the generation and identification of potential physiologically active fragments will be covered. PMID- 8457771 TI - Functional aspects of the adrenal medullary chromogranins. PMID- 8457772 TI - Processing of chromaffin granule proteins: a profusion of proteases? AB - Evidence suggests that proenkephalin and members of the chromogranin/secretogranin family of proteins are prohormone precursors, giving rise to a variety of peptides with biologic activity. However, the specific proteases responsible for cleaving these proteins in vivo have not been fully established. Several candidate proteases have been described, some of which have been shown to cleave these proteins in vitro. Proteolytic processing of the chromogranins may be particularly complex, occurring in specific tissue-dependent patterns. To account for this level of complexity several protease systems may be operative, either alone or in concert, both within the neurosecretory granule and in the extracellular space. Specific proteases which are available within neurosecretory cells or in the local extracellular environment, and which may cleave these prohormones include PC1 and PC2 (recently described members of the Kex2/furin family of endoproteases), as well as kallikrein, acetylcholinesterase, and, more recently, the plasminogen/plasmin protease system. The potential role of these specific proteases in the processing of proenkephalin and the chromogranins is discussed, in particular, in the context of possible processing clues available from recent analysis of cDNA and genomic intron/exon structure. PMID- 8457773 TI - Proto-oncogenes and signaling processes in neural tissues. AB - The study of ubiquitously expressed proto-oncogenes or tumor suppressor genes provided important insights into the second messenger signaling pathways common to neural and non-neural tissues. Therefore, it is expected that the analysis of proto-oncogenes expressed in neural tissues should probe into neurotrophic and neurotransmitter receptors, ion channels and other molecules involved in processes underlying basic physiological functions of the nervous system. This expectation is fulfilled by ample experimental evidence. Using the trk, abl and src families of tyrosine kinase encoded proto-oncogenes, we discuss here new insights into the structural and functional organization of neural tissues gained from the molecular and genetic analyses of these genes and their products. Special attention is given to the description of initial steps of signaling through the Trk receptors in response to neurotrophic factors of the Nerve Growth Factor family. The genetic analysis of the Drosophila abl gene product identified new gene products that interact with the Abl protein. This analysis illuminates the power of Drosophila genetics in dissecting components of a signal transduction pathway. The Src-family of non-receptor type protein-tyrosine kinases is discussed from the point of functional redundancy as revealed by targeted gene disruption and expression studies. The recent progress in the field of proto-oncogenes has been impressive and it is expected that proto-oncogenes will continue to provide valuable tools in the study of the complex signaling pathways that underlie the physiological functions of the central nervous system. PMID- 8457774 TI - Uridine uptake pattern in the cerebral cortex of grivet monkey. AB - Assuming that uridine uptake is correlated to RNA synthesis, and thereby to nerve cell function, the distribution of 5-[H3]-uridine-labelled nerve cell nuclei in the cerebral cortex of three hemispheres from two grivet monkeys was examined by microautoradiography. The labelling pattern for 50 cells in layers 2-6 of 10 cortical locations were different in many locations, but in each location they were generally similar. The precentral areas had relatively high labelling, while the motor cortex relatively low, paralleling the bloodflow in these regions. The labelling of layer 4 and 6 was lower than in the other layers of cortex. These measurements provide basic information about the pattern of uridine labelling on the cellular level in primate cortex from animals moving freely in the cage. PMID- 8457775 TI - Brain creatine kinase activity during ontogeny of the cichlid fish oreochromis mossambicus and the clawed toad Xenopus laevis, influence of gravity? AB - The development of creatine kinase (CK) activity was studied in the brain of cichlid fish and clawed toads. The activity of CK in the whole brain of the fish decreases immediately after hatching (stage 6) from values of about 135 nmol substrate cleaved/mg protein/min to a value of about 105 at stage 8 (5 days post hatch at 20 degrees C). With the exception of a significant peak (125 nmol) between stages 9 and 10 (7 and 9 days respectively, post hatch at 20 degrees C) and a small intermediate peak at stages 12 and 13 (about 10 days post hatch at 20 degrees C) a constant level of about 100 nmol cleaved substrate is maintained until maturity. In contrast, CK activity was determined to be 3-fold higher in the whole brain of the clawed toad. With the exception of two significant peaks at stages 47 and 49 (5 and 12 days respectively, post fertilization at 23 degrees C) a value of about 360 nmol was found during larval development and metamorphosis, as well as in the adult brain. In investigating the possible influence of gravity on CK activity during early ontogeny of the brain both animal species were exposed to hyper-gravity (3 +/- 1 g) for 7 days. A significant decrease of total CK activity of 20% was found in the fish brain and of about 5% in the toad.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457776 TI - GM-CSF as an adjunct to autologous bone marrow transplantation. AB - Patients with cancer can now benefit from intensive drug dosage. Intensive drug dosage has become more effective because of the availability of better anti emetics, hematopoietic growth factors such as granulocyte-macrophage colony stimulating factor (GM-CSF), granulocyte CSF (G-CSF), erythropoietin, etc. and improvements in hematopoietic stem cell transplantation. We have evaluated the clinical and cost effectiveness of GM-CSF in patients undergoing autologous bone marrow transplantation (AuBMT) for Hodgkin's disease. Administration of GM-CSF after AuBMT enhances myeloid and platelet recovery and is cost effective in the treatment of patients with relapsed Hodgkin's disease who received intensive chemotherapy and AuBMT. We also describe the use of various new therapeutic approaches with emphasis on clinical and cost benefit. Further work is needed to improve the route and duration of growth factor(s) infusion and the timing of the various treatments. PMID- 8457778 TI - The challenge of cancer research. AB - The challenge of cancer research can be summarized by simple statistics. In 1992, more than 1.1 million Americans are expected to develop cancer, and roughly 520,000 are expected to die from cancer. The National Cancer Institute's (NCI's) mission is to eradicate the death and suffering from cancer, to cure cancer once it starts and ultimately to prevent cancer. To this end, initiatives that promote continued development of sophisticated molecular technologies and clinical application of those technologies to the prevention, diagnosis and treatment of cancer are of surpassingly high priority. Epidemiological studies tell us that at least 30-50% of cancer is directly related to smoking, diet and environmental factors. Treatment studies indicate that significant gains in survival are possible and have already been achieved in some cancers, with promise from new drugs and other modalities (including genetic engineering) for still other cancers. Prevention strategies such as smoking reduction, diet, environmental measures, chemoprevention and vaccine development have the potential to achieve a substantial reduction in cancer mortality. This reduction, realized over two decades, would result in at least 100,000 lives saved per year in this country, and a large number can be saved just by applying what we already know. PMID- 8457777 TI - Interleukin-2: use in solid tumors. AB - Recombinant interleukin-2 (rIL-2) is a cytokine that has a central immunoregulatory role in controlling T cell function and growth. Clinical trials of rIL-2 regimens in various solid tumors have been initiated, and 337 patients at the Cleveland Clinic Foundation have been treated in a sequence of trials. The studies have involved rIL-2 or polyethylene-glycol conjugated rIL-2 (PEG-IL-2) as single agents, combinations of rIL-2 with recombinant interferon alpha, IL-4, or doxorubicin, and trials of rIL-2 with tumor infiltrating lymphocytes (TILs). These studies are summarized and involve Phase I or Phase II investigations in patients with renal cell carcinoma (191 patients), malignant melanoma (49 patients) or miscellaneous solid tumors (97 patients). Response rates in each category, respectively, were 12%, 20% and 2%. Toxicity varied depending on the regimen and generally reflected the dose and schedule of rIL-2 being employed. This series of clinical studies demonstrates the role of rIL-2 in various malignancies and documents the activity in patients with malignant melanoma and renal cell carcinoma. Additional studies to investigate potential mechanisms of antitumor activity and response determinants are underway. PMID- 8457779 TI - Population heterogeneity among cells of the megakaryocyte lineage. AB - Understanding the developmental steps in megakaryocyte differentiation requires information regarding the microenvironmental influences which direct or permit the growth and differentiation of these cells. The megakaryocyte microenvironment, like other lineages, is a complex structure comprised of the various megakaryocytic cells, the extracellular matrix (ECM) surrounding them, and the hematopoietic stromal cells which elaborate both growth factors and ECM. As a result, definition of the minimal essential requirements for megakaryocyte development is difficult. The intricacies of megakaryocyte development are further complicated by the cellular heterogeneity of both mature megakaryocytes and their precursors, as well as a differential responsiveness of these cells to hematopoietic growth factors. This review focuses on defining the various subpopulations of megakaryocytic cells and examining their functional distinctions and in vitro responsiveness to various stimuli. PMID- 8457780 TI - Role of cytokines and adhesion molecules in malaria immunopathology. AB - Cerebral malaria (CM) is the most common cause of death in severe malaria; more than two million children die of CM annually. Although the mechanisms of this neurologic complication remain poorly understood, studies in an experimental model of CM suggest that a natural body protein seems to be a major cause of this deadliest complication of malaria, a finding that could point towards new methods of treatment. We have explored the pathogenesis of CM with particular attention to the possible relationship between susceptibility or resistance to CM and cytokine expression and secretion patterns. We found that CM is associated with an increased expression of tumor necrosis factor (TNF) and interferon (IFN)-gamma and a reduced expression of interleukin-4 (IL-4) and transforming growth factor (TGF)-beta. The data obtained are consistent with a predominantly Th1 response in mice developing the cerebral complications of malaria. The overexpression of TNF in brain was also correlated with the augmented expression of adhesion molecules involved in the sequestration of leukocytes in brain vessels, a distinctive feature of CM. These observations were seen in relation to the immune status of man, in which, akin to the mouse model, a predominant Th1 response and upregulation of adhesion molecules in brain endothelium appear to be associated with susceptibility to the neurological complications of CM. PMID- 8457781 TI - Recombinant human erythropoietin (rHuEPO) for treatment of myelodysplastic syndrome. AB - Sixteen patients (ages 53 to 85) with myelodysplastic syndrome (MDS) were treated with recombinant human erythropoietin (rHuEPO) to observe its effects on hematopoiesis. All were transfusion dependent and had Hb levels less than 9.0 g/dl and less than 10% marrow blasts. Eight patients had refractory anemia (RA), one had refractory anemia with excess blasts (RAEB), and seven had refractory anemia with ringed sideroblasts (RARS). A response was defined as an increase in Hb by greater than 2 g/dl and/or a decrease in transfusion requirement by greater than 50%. Patients were considered to be evaluable if on study greater than two months. Three of thirteen evaluable patients had a response. One patient with RA had a sustained trilineage hematologic response with no evidence of disease progression. None of the patients had trouble with hypertension or with thrombotic events. This suggests than an occasional patient with MDS will respond to rHuEPO. In some patients, this may be beneficial clinically. PMID- 8457782 TI - Ability of the hemopoietic microenvironment in the induced bone to maintain the proliferative potential of early hemopoietic precursors. AB - A comparison of proliferative potential was made between spleen colony forming unit (CFU-S) from skeletal bones and those from ectopically induced ossicles. To this end, mice having two types of ectopic ossicles were used. Each animal was implanted s.c. with demineralized tooth matrix (which served as a source of bone inducing activity) and again beneath the renal capsule with a femoral bone marrow plug (which was a source of viable osteogenic cells). Those recipient mice that had developed ectopic ossicles were lethally irradiated and then reconstituted with syngeneic bone marrow cells. At various times post-reconstitution, the proliferative potential (PP) of CFU-S in skeletal bones and ectopic ossicles of mice was studied in a double spleen colony test. Hemopoietic cells from each source were injected into lethally irradiated mice; in 11 days, spleen colonies were cut out, and their cells were reinjected into secondary irradiated recipients. The PP of CFU-S was evaluated by examining the development of daughter CFU-S. It was found that, in the hemopoietic microenvironment of induced ossicles, skeletal bone and ectopic ossicles developed by viable osteogenic cells, the PP of CFU-S is maintained to the same extent. PMID- 8457783 TI - In vitro cytotoxicity of hepsulfam against human tumor cell lines and primary human tumor colony forming units. AB - Hepsulfam (sulfamic acid 1,7-heptanediyl ester, NSC 329680) is an alkylating agent currently in Phase I clinical trials. Hepsulfam was developed as an analog of busulfan, an alkylating agent that is used to treat patients with chronic myelogenous leukemia and for marrow ablation prior to bone marrow transplantation. The objective of this study was to identify the spectrum of human tumor cells that were sensitive to hepsulfam. The following three cytotoxicity assays were employed to evaluate the in vitro cytotoxic potential of hepsulfam: 1) primary human tumors were exposed to three levels of hepsulfam for a one hour or continuous exposure, and growth in soft agar was determined; 2) human non-tumor cells and tumor cell lines were compared in an assay that measured the conversion of 14C-glucose to 14CO2 as an index of viability; and 3) the toxicity of hepsulfam to hematopoietic progenitor cells was determined in a progenitor cell colony forming assay. Cytotoxicity was not observed for human tumor cells following one hour hepsulfam exposures; in contrast, marked dose dependent cytotoxicity was observed with continuous exposures. In human tumor cell lines, the cytotoxicity of hepsulfam was compared directly with busulfan at equimolar concentrations. Hepsulfam was more cytotoxic than busulfan in all cell lines tested. Cytotoxic activity was seen in lung, melanoma, kidney, breast, colon, ovary and brain tumor cells. These results, along with the information obtained from Phase I trials, will facilitate selection of patients who could receive this agent in Phase II efficacy trials. PMID- 8457784 TI - Chromosomal approaches to hematopoietic oncogenesis. AB - Cytogenetic studies have provided an important approach to the identification of genes involved in the development of human leukemias and lymphomas and the "mutational" mechanisms leading to the altered function of these genes. Molecular dissection of chromosome translocations, in both lymphoid and myeloid tumors, has been particularly productive. Involvement of the c-myc gene has been demonstrated in both B cell and T cell tumors through association with an immunoglobulin or T cell receptor locus, respectively, and more than a dozen previously unknown "oncogenes" have been identified in other lymphoid tumor subgroups and are "activated" by a similar mechanism or by formation of a "fusion" gene with a locus on a different chromosome. In myeloid tumors, dissection of the translocation in Philadelphia chromosome positive leukemias has demonstrated involvement of the abl oncogene; other genes, both known and previously unknown, are beginning to be identified in translocations that characterize other classes of myeloid leukemia. These kinds of studies are being extended to search for tumor suppressor genes in association with chromosomal deletions, and some of the new molecular data are already being usefully applied in clinical diagnosis and management. Ultimately, there may also be specific therapies developed from these recent findings, but the recognition of how many different genes are involved has also indicated that no single, simple answer will be forthcoming. PMID- 8457785 TI - To do tissue culture in two or three dimensions? That is the question. AB - Alexis Carrel introduced the in vitro culture of tissues in the beginning of the century utilizing a culture system that allowed the three-dimensional growth of tissues. Leighton improved upon this system by developing a substrate of sponge matrices. Other methods of three-dimensional culture include collagen gels and what are known as organ culture systems on filters or meshes. In addition, cell suspensions can be converted into multicellular spheroids, another form of three dimensional culture. Comparison of the three-dimensional culture methods with two dimensional culture methods has shown critical differences in the behavior of biological systems in culture. For example, in vivo-like drug responses are observed in three-dimensional but frequently not in two-dimensional cultures, indicating that drug response may be a function of tissue architecture. The in vivo mechanism of drug resistance may involve alterations in cell-cell interaction which may occur in three-dimensional culture as opposed to monolayer culture. Practical applications of three-dimensional culture include the development of a drug-response assay that correlates not only with drug resistance but also with drug sensitivity and survival of cancer patients. It has been shown that gene expression may be more in vivo-like in three-dimensional cultures than in two-dimensional monolayer cultures. For example, tumor antigens may be expressed in three-dimensional culture and not in monolayer culture. Thus, future studies utilizing three-dimensional cultures may significantly enhance our understanding of gene expression and resistance to drugs and enhance the efficacy of cancer chemotherapy by correctly predicting active drug regimens for individual patients. PMID- 8457786 TI - Phenotype and function of stromal cells cloned from the ileal Peyer's patch of sheep. AB - The ileal Peyer's patch (PP) is the major site of B cell production and immunoglobulin diversification in lambs, but the factors which regulate these processes are poorly understood. As a first step toward identifying possible regulatory mechanisms, stable long-term cultures of ileal PP stromal cells were established at the clonal level. Four distinct cell types were identified by their phenotype and growth requirements. Immunohistochemical staining confirmed that all clones were mesenchymal (vimentin+; cytokeratin-) in origin and were negative for T cell, B cell, and macrophage markers. Three cell lines were negative for major histocompatibility complex (MHC) I and II molecules, but one cell line, SCN, expressed MHC I, MHC II and CD44 molecules, and a subpopulation of SCN cells expressed BAQ44A, a B cell differentiation molecule. The four cell lines produced different types and amounts of extracellular matrix proteins, and their growth was not influenced by exogenous human interleukin 1 (IL-1), IL-2, transforming growth factor beta 1 (TGF beta 1), or bovine fibroblast growth factor (FGF) but was influenced by serum. When tested for their capacity to support lymphocyte growth, all clones produced a soluble factor(s) that was mitogenic for ileal and jejunal PP cells and thymocytes. Similar growth promoting activity was observed with culture supernatants of murine, human and bovine fibroblasts but could not be reproduced using recombinant human cytokines. Furthermore, coculture of stromal cells with ileal PP follicular B cells elicited a proliferative response unique to each stromal cell line. Coculture with increasing numbers of SCN cells inhibited B cell proliferative responses, whereas coculture with SCG2 and SCF32 cells enhanced B cell proliferative response at both low and high stromal cell densities. Ileal PP follicular B cells rapidly bound to the surface of all stromal cell clones, and this interaction was specific when compared with thymocytes or peripheral blood lymphocytes. These results suggest that ileal PP stromal cells are a phenotypically and functionally heterogeneous population that may enhance or inhibit B lymphopoiesis in the ileal PP. PMID- 8457787 TI - Recombinant human interleukin 3 in clinical oncology. AB - Interleukin 3 (IL-3) is a multipotent hematopoietic growth factor which became available as a recombinant (rh) growth factor for use in the clinic a few years ago. In dose-finding studies, this hematopoietic growth factor has been evaluated without and after standard chemotherapy. Stimulatory effects on leukocytes, neutrophils, eosinophils, monocytes, reticulocytes and platelets were observed in some studies. Chemotherapy postponement due to insufficient bone marrow recovery was less frequent when IL-3 was administered. There are some clinical studies available in which rhIL-3 is combined with rh granulocyte-macrophage colony stimulating factor (GM-CSF). The results do not clearly suggest superiority of these combinations over rhGM-CSF alone, but this may be partly due to the time scheduling of the growth factors. Administration s.c. is not inferior to i.v. Side effects mainly consist of flu-like symptoms and headache. The role of rhIL-3 after high-dose chemotherapy and autologous bone marrow reinfusion is still questionable. The addition of rhIL-3 to rhGM-CSF both administered after chemotherapy may allow a very high yield of peripheral stem cells suitable for bone marrow reconstitution after high-dose chemotherapy. rhIL-3 can stimulate leukemia tumor cell proliferation in vitro as well as proliferation of solid tumor cell lines. It is not yet clear in which way rhIL-3 combined with chemotherapy will effect tumor response and patient survival. It is too early to define the exact place of rhIL-3 in oncology. Additional studies with rhIL-3 alone and in combination with other growth factors are needed. PMID- 8457788 TI - Clinical implications of cytogenetic and molecular analyses of pediatric acute lymphoblastic leukemia. AB - The prognosis for children with acute lymphoblastic leukemia (ALL) has improved steadily over the past 20 years. Today, at least two-thirds of newly diagnosed cases are curable with intensified risk-based therapy. The challenge now is to identify, prior to or early in treatment, the one-third of patients who are destined to relapse, so that alternative therapy can be introduced sooner. Cytogenetic studies of lymphoblasts have identified recurring abnormalities of prognostic importance and pinpointed chromosomal regions for molecular analyses. Recently, molecular diagnostic techniques have been developed for the more common cytogenetic subgroups of ALL, defined by the t(1;19) and t(9;22) chromosomal translocations (approximately 10% of cases). Polymerase chain reaction (PCR) techniques can identify these clinically important subgroups in the absence of successful cytogenetic studies. PCR analysis also provides a sensitive and specific tool for the detection of minimal residual disease during apparent (clinically defined) remission. Additionally, molecular studies of cases with specific cytogenetic lesions have helped to clarify the events leading to leukemic transformation of normal lymphoid cells. It is reasonable to expect that improved therapeutic strategies will emerge from findings made with molecular diagnostic and treatment monitoring techniques. PMID- 8457789 TI - Recombinant human erythropoietin and the anemia of multiple myeloma. AB - The anemia of multiple myeloma (MM) is multifactorial, including physical replacement of normal hemopoiesis by tumor cells, renal failure and cytokines which contribute to the blunted erythropoietin (EPO) response observed in anemias of chronic disease. Recombinant EPO has been evaluated in anemic patients with stable multiple myeloma (< or = 10g% hemoglobin). Responses (> or = 2g% hemoglobin increase) were observed in 78% of 41 patients in two separate studies. Responses were associated with an increase in bone marrow erythropoietic cell compartment and reticulocytosis. Evaluation of potential parameters affecting response identified prolonged cytotoxic therapy for > 12 months, especially with alkylating agents and pre-treatment EPO levels > 100 U/L, both of which seemed to decrease the likelihood of EPO response. EPO is a safe and effective treatment for the anemia associated with MM. PMID- 8457790 TI - Qualitative content analysis: a guide to paths not taken. AB - Counting codes makes qualitative content analysis a controversial approach to analyzing textual data. Several decades ago, mainstream content analysis rejected qualitative content analysis on the grounds that it was not sufficiently quantitative; today, it is often charged with not being sufficiently qualitative. This article argues that qualitative content analysis is distinctively qualitative in both its approach to coding and its interpretations of counts from codes. Rather than argue over whether to do qualitative content analysis, researchers must make informed decisions about when to use it in analyzing qualitative data. PMID- 8457791 TI - An experiential model of learning diabetes self-management. AB - The literature on self-management in diabetes consists predominantly of investigations on compliance, behavioral modification techniques, assessment of health beliefs, and cognitive theories. Little systematic research has explored the actual experience of applying and adapting to a diabetes regimen. This qualitative study reports a diabetes self-management model (DSMM) based on interview data from 18 adults with Type I diabetes. As described and confirmed by the study participants, the DSMM is composed of sequential phases and stages that evolve over time and is influenced by four major factors: personal considerations, monitoring activities, specific cognitive skills for diabetes problem solving, and definition of control. This study provides a model that affirms the experience and effort of learning self-management and recognizes the importance of individualized regimens developed from personal experiences and perceptions of what "works for me." PMID- 8457792 TI - Apportioning illness management authority: how diabetic individuals evaluate and respond to spousal help. AB - This study explores spousal helping behavior related to diabetes management as seen from the perspective of the person with diabetes. Individuals with diabetes described spousal behaviors considered helpful in one context that were considered intrusive or unhelpful in other situations. When the helpful and unhelpful situations were compared, two factors emerged that were fundamental influences in subjects' acceptance or rejection of help and the manner in which it was accepted or refused. These factors were perceived need for help and subjects' perception of spousal motivation for action. Combinations of these factors gave rise to four distinct response patterns: grudging acceptance of help, grateful acceptance of help, respectful rejection of help, and punitive rejection of help. The impact of these response patterns on diabetes management is discussed. PMID- 8457793 TI - Managing life with a chronic condition: the story of normalization. AB - One way that families and individuals manage living with a chronic condition is to construct and live a story of "life as normal." The conceptualization of this process is based on constant comparative analysis of accounts of individuals and family members who are managing chronic conditions. The process begins with construction of the story of life as normal and continues as the story is lived over time. As the story is enacted, persons reauthor their lives. Thus the reciprocal nature of the process becomes evident. Specifically, how individuals and families construct and enact the story is discussed along with the role of health care professionals in the process and associated costs and benefits. PMID- 8457794 TI - Computer analysis of qualitative data: a comparison of three packages. AB - This article describes and compares three computer programs designed to assist in the analysis of narrative text. Ethnograph, GATOR, and Martin were compared in the context of a qualitative study of women and their husbands following mastectomy in order to (a) describe the fit between research purpose and program capabilities and (b) explore the influence, if any, of particular program features on research methods or analysis. The comparison suggests that methodological assistance provided by the programs involves differences in approach sufficient to make prior consideration of the fit between program capabilities and research purposes, methods, and style an important research decision. Descriptions of the programs and their application provide guidelines for comparison of these and other computer programs. PMID- 8457795 TI - Vance Tartar: a unique biologist. AB - Vance Tartar (1911-1991) has made major discoveries concerning morphogenesis, patterning, and nucleocytoplasmic relations in the giant ciliate Stentor coeruleus, mostly by means of hand-grafting using glass microneedles. This article provides a chronological account of the major events of Vance Tartar's life, a brief description of some of his major scientific achievements, and a discussion of his distinctive personality and multifaceted interests. It concludes with a consideration of how his unique style of life and work contributed to his equally unique scientific contributions. PMID- 8457796 TI - The Golgi apparatus of Tetrahymena thermophila. AB - Electron microscopic investigations reveal that the Golgi apparatus of Tetrahymena thermophila consists of numerous tiny dictyosomes, each consisting of one or two cisternae. The dictyosomes are localized predominantly in the cell cortex closely associated with the mitochondria, arranged in meridians alternating with the ciliary meridians. We estimated about 300-400 of these dictyosomes in the periphery of a cell, a value corresponding to the number of somatic cilia per cell. Cytochemical assays of thiamine pyrophosphatase and acid phosphatase, both marker enzymes of trans Golgi cisternae, resulted in deposits of lead or cerium phosphate in the outermost cisternae of the dictyosomes. In addition, cisternae located at the bases of the basal body/parasomal sac arrangements are stained. This indicates that these cisternae may belong to the Golgi apparatus of the cell. PMID- 8457797 TI - Septata intestinalis N. G., N. Sp., an intestinal microsporidian associated with chronic diarrhea and dissemination in AIDS patients. AB - Intestinal microsporidiosis in patients diagnosed with acquired immunodeficiency syndrome (AIDS) and having chronic diarrhea was first reported in 1985 and the associated microsporidian was named Enterocytozoon bieneusi. The intracellular developmental cycle of E. bieneusi in enterocytes has been demonstrated and many cases have been reported worldwide. This report presents the life cycle of a second intestinal microsporidian, associated with the same symptoms, in five AIDS patients. This new microsporidian also infects enterocytes but its pathology and morphology differ from that of E. bieneusi. It involves lamina propria macrophages, fibroblasts, and endothelial cells and can disseminate to infect other parts of the body, e.g. the kidney and gall bladder. The parasite cycle includes development of rounded uninucleate and elongated bi- or tetranucleate cells without the formation of plasmodial stages. Sporogony is similar to the more typical development of microsporidia with sporoblast morphogenesis occurring after the last cell division. The development of cells within chambers of a septate, honeycomb-like, parasite-secreted fibrillar network and surrounded by a parasitophorous vacuole, however, is unique to this microsporidian, justifying the establishment of a new genus and species, Septata intestinalis n. g., n. sp. PMID- 8457798 TI - In vitro susceptibility of Acanthamoeba culbertsoni to inhibitors of folate biosynthesis. AB - The effects of different sulphonamides, dihydrofolate reductase inhibitors and other inhibitors of folate metabolism on growth of Acanthamoeba culbertsoni in a chemically defined medium are reported. Among the sulphonamides, sulphamethoxazole and sulphadiazine were most effective followed by sulphanilamide and sulphaguanidine. Inhibition by each sulphonamide was reversed by p-aminobenzoic acid as well as folic acid. 7-Methylguanosine, a pteridine synthesis-inhibitor, did not inhibit multiplication of A. culbertsoni. Among the dihydrofolate reductase inhibitors, pyrimethamine blocked the amoebic growth at 100 micrograms/ml, while trimethoprim and cycloguanil palmoate failed to cause significant inhibition of growth even at 250 micrograms/ml. Metoprine inhibited amoebic growth completely at 50 micrograms/ml. Methotrexate and a thymidylate synthetase inhibitor 5-fluorouracil inhibited growth strongly, with IC50 values (the concentration of the drug which causes 50% inhibition of the growth at 72 h) of 1.97 and 2.45 micrograms/ml, respectively. Inhibition by methotrexate, metoprine or 5-fluorouracil could not be reversed by folic acid, folinic acid, thymidine, or folinic acid plus thymidine. The results indicate unusual features in A. culbertsoni folate metabolism. PMID- 8457799 TI - Immunological detection of cytoskeletal proteins in the exoerythrocytic stages of malaria by fluorescence and confocal laser scanning microscopy. AB - Using monospecific antibodies, the presence and distribution of tubulin, actin, myosin, intermediate filaments, and lamins were examined in the exoerythrocytic liver schizont of Plasmodium berghei by conventional indirect fluorescent antibody methods and confocal laser scanning microscopy. The binding reactivity of the antibodies to parasite proteins was determined by Western blot analysis. The localisation of all antibodies in control host hepatocytes followed expected distributions in both uninfected and infected hepatocytes; by contrast, reactivity to the exoerythrocytic schizont was variable. The parasite reacted positively with selected anti-tubulin, -actin, and -myosin antibodies in both fluorescence and Western blot analysis. Anti-lamin antibodies were positive by confocal indirect fluorescent antibody labelling, but no labelling was detected with anti-intermediate filament antibody. Within the technical limits of resolution of the methods as applied to asynchronous parasite infections, not one of the antibodies reacting positively with the parasite by the indirect fluorescent antibody technique could be shown to identify unequivocally the classic architectural features associated with their respective target organelles, i.e. microtubules, stress-fibres or the nuclear envelope. PMID- 8457800 TI - Pyrimidine salvage pathways in Toxoplasma gondii. AB - Pyrimidine salvage enzyme activities in cell-free extracts of Toxoplasma gondii were assayed in order to determine which of these enzyme activities are present in these parasites. Enzyme activities that were detected included phosphoribosyltransferase activity towards uracil (but not cytosine or thymine), nucleoside phosphorylase activity towards uridine, deoxyuridine and thymidine (but not cytidine or deoxycytidine), deaminase activity towards cytidine and deoxycytidine (but not cytosine, cytidine 5'-monophosphate or deoxycytidine 5' monophosphate), and nucleoside 5'-monophosphate phosphohydrolase activity towards all nucleotides tested. No nucleoside kinase or phosphotransferase activity was detected, indicating that T. gondii lack the ability to directly phosphorylate nucleosides. Toxoplasma gondii appear to have a single non-specific uridine phosphorylase enzyme which can catalyze the reversible phosphorolysis of uridine, deoxyuridine and thymidine, and a single cytidine deaminase activity which can deaminate both cytidine and deoxycytidine. These results indicate that pyrimidine salvage in T. gondii probably occurs via the following reactions: cytidine and deoxycytidine are deaminated by cytidine deaminase to uridine and deoxyuridine, respectively; uridine and deoxyuridine are cleaved to uracil by uridine phosphorylase; and uracil is metabolized to uridine 5'-monophosphate by uracil phosphoribosyltransferase. Thus, uridine 5'-monophosphate is the end-product of both de novo pyrimidine biosynthesis and pyrimidine salvage in T. gondii. PMID- 8457801 TI - Exoerythrocytic development of Plasmodium gallinaceum sporozoites in a chicken fibroblast cell line and inhibition of the cell invasion by specific anti sporozoite monoclonal antibodies. AB - Cultivation of the Plasmodium gallinaceum exoerythrocytic forms from sporozoites was attempted in three different cell lines: HEPG2-A16 (from a human hepatoma), VERO (monkey kidney epithelial cells) and SL-29 (chicken embryo fibroblast cells). The sporozoites invaded all three cells types but their development into exoerythrocytic forms occurred only in the SL-29 cells. In the presence of specific monoclonal antibodies against the major circumsporozoite protein, there were varying degrees of inhibition of parasite invasion of the SL-29 cells. Of seven monoclonal antibodies tested, two completely inhibited cell invasion at high concentrations and caused intense inhibition at concentrations as low as 2.5 micrograms/ml, four caused intense inhibition at these various concentrations, and one had no effect on sporozoite invasion. PMID- 8457802 TI - Fine structure observations of phagotrophic activity by plasmodia of Physarum polycephalum. AB - Scanning electron microscopic observations of feeding plasmodia show three characteristic features: 1) extension of multilobed pseudopodia protruding from the leading edge of the plasmodium as it advances onto the surface of a food particle, 2) confluence of the lobes to form a sheath-like pseudopodium attached to the surface of the food particle, and 3) protrusion of small nodules with thin lamellar projections from the leading edge of the plasmodium. Sections through freeze-dried preparations of the feeding plasmodium exhibit a highly convoluted under surface in contact with loosened starch grains that appear to be released by extracellular digestion. The cytoplasm, viewed by transmission electron microscopy, contains branched, internally penetrating canals (ca. 2 microns wide) enclosing engulfed starch grains. Starch grains in the deeper part of the canals are more electron dense and appear to be digested. Micropseudopodia (70-80 nm dia.), projecting from the surface of the canals, protrude toward and into the ingested starch grains. Digestive marker enzyme (acid phosphatase) activity was detected cytochemically in food particles penetrated by micropseudopodia indicating a digestive role for these structures not reported previously. PMID- 8457803 TI - Light and electron microscope observations on presporogonic and sporogonic stages of Sphaerospora epinepheli (Myxosporea) in grouper (Epinephelus malabaricus). AB - Presporogonic (blood) stages of Sphaerospora epinepheli Supamattaya, Fischer Scherl, Hoffmann, Boonyaratpalin, 1990 were observed in the circulating blood, sinus of kidney, glomerurar capillaries and liver arteries of grouper Epinephelus malabaricus. The earliest detectable stage was a primary cell with one secondary cell. After cell divisions, nine to 16 secondary cells were found in one primary cell. Ultrastructural examination revealed electron-dense bodies (118-145 nm) in the cytoplasm of primary cells. Sporogonic stages and spores were located in Bowman's space and in kidney tubule lumens. Electron micrographs revealed a similar pattern of spore development as described from other Sphaerospora spp. Kidneys infected with S. epinepheli showed highly vacuolated tubular epithelial cells and severely affected renal corpuscles. PMID- 8457804 TI - Immunological characterization of trichocyst proteins in the ciliate Pseudomicrothorax dubius. AB - Ejectable trichocysts were isolated from the ciliate Pseudomicrothorax dubius. Polyclonal antibodies were raised against three groups of trichocyst proteins: G1 (30-31 kDa), G2 (26-27 kDa) and G3 (15-20 kDa). By indirect immunofluorescence, the three antisera strongly label the shafts of ejected trichocysts and the proximal ends of condensed trichocysts within the cells. By immunogold labeling for electron microscopy, the three sera specifically recognize the shafts of both extended and condensed trichocysts and shaft precursors in pretrichocysts as well. On one-dimensional immunoblots of isolated trichocysts, anti-G1 serum recognizes the G1 proteins, anti-G2 serum detects G2 proteins and some G1 proteins, and anti-G3 serum reacts with 15 bands, mainly the G3 and (30-41)-kDa proteins. In cells with and without trichocysts, the sera recognize non-ejectable trichocyst proteins at 41-42 kDa and 47 kDa. On two-dimensional immunoblots of isolated trichocysts, anti-G1 serum labels proteins with a pI of 4.75-5.7, anti G2 serum labels proteins with a pI of 4.75-6.25 and anti-G3 serum labels proteins with a pI of 4.7-6.6. Analyses of cells with and without trichocysts allow identification of possible precursors between 41 and 47 kDa. Some are in the same pI range as their putative products, but others, labeled by anti-G3 serum, are less acidic than most of their mature products. PMID- 8457805 TI - Overuse injury and growing bones: the young athlete at risk. AB - Increasing numbers of children are becoming involved in competitive sport. International trends in pre-adolescent sports participation are mirrored in New Zealand, where promising young athletes are being exposed to high-intensity training from an earlier age. As a consequence, overuse injuries which were traditionally described in more mature athletes are now becoming recognized in pre-adolescents. The immature musculoskeletal system is less able to cope with repetitive biomechanical stress. Sites of overuse injury reflect the sites of rapid musculoskeletal development. It therefore behoves all medical practitioners, but particularly those in primary care, to be aware of the young athlete at risk. Inherent in the presentation of such musculoskeletal insult there often lurks an over-enthusiastic parent. We are all well reminded of the covert pressures adults may bring to bear upon children. Psychological, as well as physical injury often results. PMID- 8457806 TI - Abdominal muscle training in sport. AB - This paper evaluates several abdominal exercises, and highlights factors which are important for their safe prescription and effective use. The function of the abdominal muscles and hip flexors is considered, and the importance of the infra umbilical portion of the rectus abdominis is emphasized. The effects of flexion on the lumbar spine are outlined. The trunk curl, sit-up, and straight leg raise are analysed, together with modifications of these exercises. The effect of foot fixation and hip flexion during the performance of the sit-up is discussed. The sit-up performed with foot fixation, and the bilateral straight leg raise can compound hip muscle imbalance, and both hyperextend and hyperflex the lumbar spine and are therefore not recommended. The importance of muscular control of pelvic tilt is considered with reference to muscle imbalance around the pelvis. It is recommended that a musculoskeletal assessment should be performed before prescribing abdominal exercises. Exercise therapy to re-educate control of pelvic tilt is described. Intra-abdominal pressure, and the effects of abdominal exercise on this mechanism, and lumbar stabilization are examined. The importance of training specificity is stressed. PMID- 8457807 TI - The role of massage in the management of the athlete: a review. AB - Massage has been a therapeutic modality in all cultures since early civilization and has had a long tradition of use in the sporting context. However, there has been a paucity of scientific evidence of the physiological, psychological and therapeutic effects of commonly used massage techniques. This paper reviews the early and more recent studies on the effects of massage and also the more recent literature on its use on the sports person. Little agreement was found in English publications of the efficacy of massage and there were contradictory findings as to the optimum technique and length of time of application. It is clear that the role of massage - a time-consuming technique for a physiotherapist to perform - needs to be evaluated further in order to resolve some contentious issues arising about this mode of treatment and to justify its use. PMID- 8457808 TI - Sports medicine and national fitness. PMID- 8457809 TI - Fluid replacement in sport and exercise--a consensus statement. PMID- 8457810 TI - A complication of internal fixation rods in sport. PMID- 8457811 TI - Pneumomediastinum after rugby training. PMID- 8457812 TI - Response of unacclimatized males to repeated weekly bouts of exercise in the heat. AB - The purpose of the present study was to determine if there is an acclimation effect when unacclimatized males exercise in the heat at weekly intervals. Five subjects performed four exercise bouts, each lasting 1 h at 55% VO2max. The first trial was in moderate conditions (mean(s.d.) temperature (Ta) = 22.0(0.8)degrees C; mean(s.d.) relative humidity (rh) = 67(6)%) and the subsequent three trials were carried out at weekly intervals in the heat (mean(s.d.) Ta = 34.6(0.6)degrees C; mean(s.d.) rh = 60(7)%). There were no significant differences between trials in the heat for heart rate, rectal temperature, skin temperature or VO2 (repeated measures analysis of variance), and total sweat loss (one-way analysis of variance). As changes in these variables are seen with heat acclimation it was concluded that there was no heat acclimation effect and separating exercise bouts by 1 week was a valid method for comparing the effects of different treatments on unacclimatized males during exercise in the heat. PMID- 8457813 TI - Gender difference in anaerobic capacity: role of aerobic contribution. AB - The purpose of this study was to evaluate effects of gender on anaerobic and aerobic contributions to high-intensity exercise. A group of 38 subjects (22 women, 16 men) performed modified Wingate tests against resistances of 0.086 kg kg-1 body mass (0.844 N kg-1) for women and 0.095 kg kg-1 body mass (0.932 N kg 1) for men. The aerobic contribution to total work performed was determined from breath-by-breath analyses of expired gases during each test. Total work in 30 s was 30% lower (Student's t test; P < 0.01) in women than men (211 +/- 5 J kg-1 versus 299 +/- 14 J kg-1). Aerobic contribution was only 7% lower (P = 0.12) in women than men (53 +/- 1 J kg-1 versus 57 +/- 2 J kg-1). The anaerobic component of the work performed, determined by subtraction of the aerobic component from total work in 30 s, was 35% lower (P < 0.01) in women than men (158 +/- 5 J kg-1 versus 242 +/- 15 J kg-1). It is concluded that, because women provide a relatively higher (P < 0.01) portion of the energy for a 30-s test aerobically than men (25% versus 20%), total work during a Wingate test actually underestimates the gender difference in anaerobic capacity between women and men. PMID- 8457814 TI - The Johnson antishear device and standard shin pad in the isokinetic assessment of the knee. AB - Isokinetic training and assessment of the knee joint has been the mainstay of rehabilitation, especially in patients with anterior cruciate ligament deficiency. Besides the original shin pad used, the antishear device was introduced by Johnson in 1982. This device has been shown biomechanically to prevent excessive anterior translation of force on the tibia during training. However, there is a need to compare the antishear device and the standard shin pad in the isokinetic assessment. Hence, the major objective of this study is to define, if any, the difference in patient assessment between the new double pad device and the old single shin pad. Ten subjects with no previous history of injury on either knee were tested with the Cybex Isokinetic Dynamometer. There were four men and six women and the mean age was 25.2 years. They were randomized into different test sequences with different shin pads at different speeds. Correlation and paired t tests (P) were performed to find out the correlation and difference between the two devices. There was significant difference in performance assessment between the two devices in knee extension (P < 0.05) but no significant difference in knee flexion (P > 0.05). There was also a high correlation (r > 0.75) between the two devices. It is concluded that because of the significant difference of data generated between the two devices, it is important to select one single device with each patient during a series of testings. PMID- 8457815 TI - Heart rates during competitive orienteering. AB - This study investigated the heart rate profiles of 16 experienced, competitive orienteers (aged 15-62 years) during three competitive events. Each competitor was assessed over three different types of course which were classified as: fast run (FR), slow run (SR) and highly physical (HP). The results showed that all subjects recorded heart rates that were between 140 and 180 beats min-1 for the majority of each event (irrespective of age or course type). The heart rate data indicated that the activity was largely aerobic but varied in intensity, with phases of strenuous anaerobic work. The type of course was shown significantly (analysis of variance; P < 0.001) to affect the mean heart rate attained by each orienteer (FR = 160, HP = 158, SR = 150 beats min-1), with courses that required more technical skill and hence slower running producing lower mean heart rates; although the general physical demands were similar for all courses. The older orienteers (> 45 years) recorded heart rate profiles that were similar to those of the young orienteers with no correlation being found between age and mean heart rate while exercising. PMID- 8457816 TI - The sports hernia: a cause of chronic groin pain. AB - The management of chronic pain in sportsmen and women requires consideration of a wide differential diagnosis. A syndrome caused by a distension of the posterior inguinal wall is described, effectively an early direct inguinal hernia. The diagnosis can be made from certain aspects of the history and examination, which are described. The results of surgical repair to the posterior inguinal wall are excellent. The procedure was carried out on 14 sportsmen and one woman. There is an 87% return to full sporting activity, with a follow-up of 18 months to 5 years. The remaining 13% were improved by the repair. Many of the athletes had received other treatments without success. The sports hernia should be high on the list of differential diagnoses in chronic groin pain. PMID- 8457817 TI - An evaluation of a bioelectrical impedance analyser for the estimation of body fat content. AB - Measurement of body composition is an important part of any assessment of health or fitness. Hydrostatic weighing is generally accepted as the most reliable method for the measurement of body fat content, but is inconvenient. Electrical impedance analysers have recently been proposed as an alternative to the measurement of skinfold thickness. Both these latter methods are convenient, but give values based on estimates obtained from population studies. This study compared values of body fat content obtained by hydrostatic weighing, skinfold thickness measurement and electrical impedance on 50 (28 women, 22 men) healthy volunteers. Mean(s.e.m.) values obtained by the three methods were: hydrostatic weighing, 20.5(1.2)%; skinfold thickness, 21.8(1.0)%; impedance, 20.8(0.9)%. The results indicate that the correlation between the skinfold method and hydrostatic weighing (0.931) is somewhat higher than that between the impedance method and hydrostatic weighing (0.830). This is, perhaps, not surprising given the fact that the impedance method is based on an estimate of total body water which is then used to calculate body fat content. The skinfold method gives an estimate of body density, and the assumptions involved in the conversion from body density to body fat content are the same for both methods. PMID- 8457818 TI - Trauma on the Isle of Man. AB - The Isle of Man Tourist Trophy motorcycle races remain one of the most popular venues for motorcycle races. This is despite the reduced status of the event. The reason for the loss of world championship and formula one status is the nature of the road racing circuit itself. The twisting narrow roads are only closed to the public at certain times during the practice and race weeks. Motorcycling visitors to the event attempt to emulate their heroes on machines capable of high speeds. Casualties from both visitors and racers are dealt with efficiently by an expanded medical service. This includes the use of an aeromedical evacuation helicopter. Casualties from the visitors exceeded those from the racers themselves during the period reported. PMID- 8457820 TI - The role of radiography and computed tomography in the diagnosis of acute dislocation of the proximal tibiofibular joint. AB - A cadaveric study was undertaken to determine the best radiographic method of diagnosing dislocation of the proximal tibio-fibular (PTFJ) joint. Three pairs of cadaver knees were used, the right side serving as a control in each case. Plain radiographs, antero-posterior (AP) lateral and 45 degrees oblique films, and axial computed tomography (CT) scans were obtained with the joints in each of three positions: (1) anatomical, (2) dislocated anteriorly and (3) dislocated posteriorly. Similar views were obtained in the control joints with the PTFJ undisturbed. The radiographs were assessed by eight independent observers and the results were analysed. The diagnostic accuracy with plain AP and lateral radiographs was 72.5%. This was unchanged with the addition of oblique views, but improved to 82% with the control films and 86% with the axial CT scans. The authors conclude that in the diagnosis of suspected dislocation of the PTFJ, axial CT scanning is the investigation of choice. Plain AP, lateral and comparison views are useful but less accurate, while oblique views are unhelpful and unnecessary. PMID- 8457819 TI - Patients' perception of the hysterosalpingogram: the initial stages of the audit cycle. AB - A prospective study of 98 consecutive hysterosalpingogram examinations was undertaken to evaluate patients' understanding of the examination, to assess their anxiety levels and to identify any factors where improvements might alleviate this anxiety. This was achieved by employing three simple questionnaires, two being completed by the patient (before and after the examination), the third being completed by the radiologist who recorded clinical and technical details. In this study the majority of patients knew why the examination was being performed, although only 50% had received an explanation of the technique prior to their arrival in the department. Anxiety levels associated with the examination were high. The importance of a sympathetic approach by the radiologist prior to the examination was highlighted, and it was found that time delays contributed to the anxiety level. PMID- 8457821 TI - Metaphyseal abnormalities in fibrodysplasia ossificans progressiva. AB - Fibrodysplasia ossificans progressiva (FOP) is a rare, congenital disorder characterized by diffuse ossification of extraskeletal connective tissue. The classical features and progression of the disease are described and three cases are presented which fall into the general pattern of FOP clinically and radiologically. A constant feature seen was a slight metaphyseal flaring with spiking at the edges of the metaphyses, compatible with minor alteration in bone morphology during growth. These changes cannot be seen after epiphyseal fusion. The major abnormalities persist into adult life. PMID- 8457822 TI - The efficacy of a single posteroanterior radiograph in the assessment of metastatic pulmonary melanoma. AB - Posteroanterior (PA) and lateral chest radiographs are performed as part of the routine staging and follow-up investigation of patients with malignant melanoma. We have assessed the contribution of the lateral chest radiograph in the follow up of 227 consecutive patients with proven malignant melanoma. In only once case was an abnormality evident on the lateral radiograph which was not previously detected on the PA films. Our department, as a result of this study, has discontinued the routine use of lateral chest radiography in the follow-up of patients with malignant melanoma. PMID- 8457823 TI - Pyogenic sacroiliitis, the missed diagnosis? AB - Pyogenic sacroiliitis is considered to be an uncommon infection, which is often diagnosed late because of poor localization of symptoms and normal plain radiographs at presentation. Nine cases aged between 20 months and 14 years who presented with sacroiliitis over a 7 year period are reviewed retrospectively. Isotope bone scanning is a useful technique in establishing early diagnosis and its relationship to other diagnostic imaging modalities is discussed. By routinely obtaining views of the entire pelvis in children presenting with hip pain and a limp, pyogenic sacroiliitis may be detected more frequently. PMID- 8457824 TI - An audit of comparative views in elbow trauma in children. AB - A comparative radiograph of the contralateral elbow was obtained in only 30 (2.5%) of children examined after elbow trauma. Interpretation by junior clinical staff was changed in only three children (0.25%). Radiological review of the ipsilateral elbow alone altered diagnosis in six (20%) of the 30 children referred for comparative views and agreed with the final clinical diagnosis in 29 (97%). Comparative views were requested by inexperienced clinical staff in 28 (95%) of cases and were unnecessary in all patients. A senior radiological or clinical opinion would have resolved problems at interpretation. PMID- 8457825 TI - A blood pressure independent index of aortic distensibility. AB - A non-invasive Doppler ultrasound technique for the assessment of aortic compliance based on the in vivo measurement of pulse wave velocity along the thoraco-abdominal aortic pathway is described. An approach for correcting for the effect of blood pressure on aortic compliance is considered. The derivation of an index of distensibility, Cp, which is independent of blood pressure is provided and applied to data collected from 58 normal, healthy volunteers. Medical disorders such as atherosclerosis, diabetes mellitus and familial hypercholesterolaemia have all been shown to affect arterial distensibility. We suggest that the clinical measurement of Cp may be a useful, non-invasive tool for assessing such patients' susceptibility to atheromatous arterial disease as well as for monitoring their response to therapy. PMID- 8457826 TI - The development of equipment for the technical assessment of respiratory motion induced artefacts in MRI. AB - A device and technique to study the effects of respiratory motion on the quality of magnetic resonance images is proposed. The construction of the device enables a variety of test objects to be mounted and used in the evaluation of imaging parameters that may be affected by motion. The equipment is constructed of cast acrylic and the movement is actuated and controlled pneumatically thus ensuring that there are no interactions with the magnetic field and radiofrequency detection system to cause further image artefacts. Separate studies have been performed, using ultrasound, to assess the degree and rate of movement of organs owing to respiration in order to derive the motion parameters for the apparatus. Preliminary results indicate that the technique produces motion induced artefacts simulating those which are the result of the effects of respiration. PMID- 8457827 TI - The efficacy of lead shielding in megavoltage radiotherapy. AB - The dose received by anatomical structures which are apparently shielded by lead blocks during a course of megavoltage radiotherapy may not be negligible. The dose has three main components; there is that due to radiation transmitted through the shielding block, that due to radiation scattered within the patient and that due to radiation scattered prior to reaching the patient and so circumventing the shield. A calculation method which separates the three components has been investigated and the results have been compared with measurements in a wide range of test situations for both cobalt-60 and 6 MV photon beams. The method of calculation predicts the dose behind the shielding block with acceptable accuracy in all the conditions investigated. PMID- 8457828 TI - Modification of late dermal necrosis in the pig by treatment with multi wavelength light. AB - Low-level light from a multi-wavelength light source has been used to prevent late X-ray-induced dermal necrosis in the pig. Skin fields, measuring 4 cm x 4 cm on the flank, were irradiated with graded doses of X rays and the incidence of late dermal necrosis at 10-16 weeks after irradiation was scored. The control skin sites were irradiated only with 250 kV X rays but the test skin sites were subsequently exposed to low-level light. Local light exposure was from an array of gallium aluminium arsenide diodes, which produced wavelengths of 660, 820, 880 and 950 nm, pulsating at 5 kHz. Light treatment was given three times a week, from 6-16 weeks after X irradiation. Each treatment session was 1 min, which was equivalent to energy density of 1.08 Jcm-2. Light treatment increased the ED50, the dose which causes dermal necrosis in 50% of the irradiated skin fields, from 20.10 +/- 0.12 Gy to 21.94 +/- 0.30 Gy. This difference, although small, was highly significant (p < 0.001) and was equivalent to a dose modification factor (DMF) of 1.09. The effect of light treatment was minimal at incidence levels of less than the 50% but greater at higher levels of effect. These findings suggest that low-level light, when applied appropriately, may be useful in the prevention of late X-ray-induced damage to the dermis. PMID- 8457829 TI - Technical note: compensation for field non-uniformity on a mammographic X-ray unit. PMID- 8457830 TI - Technical note: assessment of X-ray field alignment in mammography. PMID- 8457831 TI - Case report: pseudoaneurysm of transplant hepatic artery: a late presentation. PMID- 8457832 TI - Case report: squamous cell carcinoma of the nail bed. PMID- 8457833 TI - Case report: cervical intervertebral foramen widening caused by vertebral artery tortuosity--diagnosis with MR and colour-coded Doppler sonography. PMID- 8457834 TI - Case report: clear cell adenocarcinoma of the vagina: MR features. AB - Clear cell adenocarcinoma (CCA) of the vagina and the cervix is a rare tumour. Since 1971 its increased incidence has been ascribed to intrauterine exposure to diethylstilboestrol (DES) and as a consequence the US Food and Drug Administration has banned the use of all DES-type medications during pregnancy. We report a case of CCA demonstrated by magnetic resonance imaging. PMID- 8457835 TI - Case report: impaired rectal emptying caused by perineal herniation of the rectum: defaecographic demonstration using oblique projections. AB - Defaecography is usually performed in the lateral projection alone. We present a case of perineal herniation of the rectum, previously unreported, demonstrated by defaecography in oblique projections. PMID- 8457836 TI - Case of the month: a multisystem malabsorption. PMID- 8457837 TI - Short communication: ultrasonographic placental grade and thickness: associations with early delivery and low birthweight. PMID- 8457838 TI - Use of ultrasound in osteomyelitis. PMID- 8457839 TI - Altered dopamine receptor mediated signal transmission in the striatum of aged rats. AB - Striatal membranes of very old (40 months) as against young (3 months) female Wistar rats were used. Binding saturation experiments with [3H]SCH 23390 at the dopamine (DA) D1 receptor (D1) and [3H]spiperone at the DA D2 receptor (D2) revealed no change in the affinity (Kd) but a significant decrease in the density (Bmax) of D1 (-31%, P < 0.005) and of D2 (-22%, P < 0.05), respectively, in the aged vs. young striata. Displacement of either [3H]SCH 23390 or [3H]spiperone binding by DA displayed biphasic curves. The Hill coefficient (nH) was significantly increased in the senescent compared with the young of D1 (0.72 +/- 0.04 vs. 0.61 +/- 0.03, P < 0.025) but unchanged of D2 (0.49 +/- 0.04 vs. 0.51 +/ 0.02). The proportion of the high-affinity agonist binding state (Rhigh) was significantly decreased (P < 0.025) in the older (20.9 +/- 3.2%) in comparison with the young (30.6 +/- 2.0%) in D1 but increased non-significantly in D2 (47.9 +/- 2.6 vs. 40.5 +/- 5.1%). Calculating the resulting Bmax from Scatchard and displacement analyses of each single aged and young animal revealed a highly significant reduction (P < 0.001) of the high-affinity agonist binding state of D1 (-53%) as well as a non-significant reduction of D2 (-8%) in the older. Simultaneously, a significant 57% decrease (P < 0.01) in the adenylate cyclase (AC) activity stimulated by 10 microM DA in the senescent compared with the young animals was monitored. The DA stimulation of AC was reversed in both cases by the addition of 200 nM of the D1 antagonist SCH 23390. PMID- 8457840 TI - Characteristic firing behavior of cell types in the cardiorespiratory region of the nucleus tractus solitarii of the rat. AB - The present in vitro study was performed to characterize neurons within dorsal regions of the nucleus tractus solitarii (NTS), principally at the level of area postrema, and known to receive inputs predominantly from cardiovascular and respiratory afferents (i.e. cardiorespiratory NTS). This report describes 4 classes of neurons (S1-S4) that were silent at their resting membrane potential and received relatively short (< 3.6 ms) and consistent latency synaptic inputs (+/- 0.4 ms) comprising either an EPSP or EPSP/IPSP sequence following low intensity electrical stimulation of the solitary tract (ts). Intracellular recording with sharp electrodes were used to characterize neuron types based on their different firing response patterns to injection of depolarizing current. S1 cells showed a single action potential; S2 fired repetitively; S3 produced a 2-5 spike burst coincident with the start of the current pulse and S4 neurons showed delayed excitation. Accommodation of firing frequency was seen in S2, S3 and some S4 cells. The voltage dependency of the different discharge patterns of the 4 cell groups was tested by current pulse stimulation at different holding potentials. However, in the majority of cells in any one cell class the firing pattern was qualitatively similar. Based on these findings it is suggested that the different firing characteristics reflect differences in intrinsic membrane properties between neuron classes. Representative examples from each of the defined cell classes were further studied in current and voltage clamp using the whole cell patch technique to define the presence and role of certain ionic currents in the firing response patterns of the 4 cell groups. In the current clamp configuration the firing behavior of S1 neurons (single spiking) was unaltered during exposure to 4-aminopyridine (4-AP; 2 mM), cobalt chloride (Co; 5 mM), norepinephrine (NE; 20 microM) and muscarine chloride (50 microM). It is suggested that the relatively low excitability of this neuron is due a persistent outward current which occurred at -40 mV during depolarizing voltage steps in the voltage clamp configuration. A common characteristic of S2 neurons (repetitively firing) was that they showed accommodation during current injection which was greatly attenuated in the presence of Co or NE. In addition, 4-AP slowed the firing frequency, reduced the afterhyperpolarization and broadened the spike width of S2 cells. Interestingly, the amount of accommodation observed in S2 cells was variable for cells of this class and was proportional to the magnitude of a Co-sensitive inward current present during depolarizing voltage steps between -45 to -5 mV.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8457841 TI - Computational modeling of neuronal dynamics for systems analysis: application to neurons of the cardiorespiratory NTS in the rat. AB - The study constructs computational models of neurons in order to examine the contribution that their response dynamics may make to functional properties at the system level. As described in the accompanying study, neurons in the cardiorespiratory nucleus tractus solitarii (NTS) of the rat were recorded in vitro. When these cells were intracellularly injected with a constant current pulse, spike discharge patterns and subthreshold voltage trajectories were observed that were time- and voltage-dependent. The accompanying manuscript describes these dynamic responses in 4 classes of putative second-order cells that appear to receive direct primary afferent input, and a previous paper described two populations of rhythmically firing interneurons, one of which is intrinsically auto-active. In the present manuscript experimental neuronal voltage response data was collected across a current injection series for the S3 neuron type described in the accompanying study and for the auto-active neuron described previously. Using this data, computational model neurons have been constructed for these two neurons by using membrane ion channels to produce and match the observed neuronal voltage behavior. The channels were those implicated in the dynamic responses observed in the companion study, and include gNafast, gKdr, gKA, gKCa, gKAHP, gKM, gCaT and gCaL. The description of channel kinetics follows the Hodgkin-Huxley form. Different neuronal sources from the literature of channel kinetics were investigated and assembled into a 'channel kinetics library' from which both neuron models were tuned, primarily by adjusting the maximum channel densities, g, and time-dependence of kinetics. Methods are described for tuning the channel kinetics library to match various physiological responses. This approach created neuron models that were able to closely replicate the observed complex voltage and spiking responses of the two very different cardiorespiratory NTS neurons. The interaction of voltage- and calcium dependent conductances were analyzed for their functional contributions by tuning their kinetics. Specific parameters are given that account for the behavior of each model. Sensitivity analyses by perturbing KCa and KA are shown for both neurons, and I/F curves are presented for the auto-active neuron's stimulated and recorded responses. The potential systems-level functional implications resulting from the different kinetics is demonstrated by driving the S3 model neuron in simulation with the pattern of input produced by model primary baroreceptor afferents. The limitations and significance of this approach are discussed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8457842 TI - The role of wet-dog shakes during amygdaloid electrical and methionine-enkephalin kindling in the rat. AB - The role of wet-dog shakes (WDS) in the kindling phenomenon was investigated in the rat using amygdala (AM) electrical kindling (E-K group), methionine enkephalin (ME) chemical kindling (ME-K group) and ME-chemical kindling after the completion of electrical kindling (E-M group). The AM electrical kindling was carried out with 200 microA stimulation. Repeated microinjections of 10 micrograms ME into the AM were given for ME chemical kindling. EEG and behavioral seizures were recorded from the beginning of the electrical stimulation or ME microinjection to 2 min after the end of the after-discharge (AD). The mean number of WDS in ME-K and E-M groups during the chemical kindling, in contrast to that in E-K group, was significantly decreased as the kindling stages progressed. In the ME-K group, WDS completely disappeared when the stage developed into stage 5. In all the three groups, the maximum incidence of WDS in each stage appeared near the termination of AD, which was accordant with the end of the convulsive seizures. These results suggest that WDS may be associated with the kindling stage and the end of the convulsive seizure or the AD. Furthermore, the disappearance of WDS could be a behavioral index of the fully kindled state in some kinds of kindling models. PMID- 8457843 TI - Cortical refractoriness to N-methyl-D,L-aspartic acid (NMA) stimulation in the lactating rat: recovery after pup removal and blockade of progesterone receptors. AB - We have previously reported that lactating rats, unlike cycling rats, are refractory to N-methyl-D,L-aspartic acid (NMA), but not kainate, in terms of behavioral responses and activation of cFos expression in the neocortex and hippocampus. To study the factors involved in the suppression of cortical activation in lactating rats in response to NMA, we examined the effects of removing either the suckling stimulus and/or progesterone. The degree of cFos expression was used as a marker for cortical activation. Whereas control suckled animals exhibited little or no cFos activation in the piriform cortex in response to NMA, cycling rats showed a high degree of activation. Blockade of the effects of progesterone or removal of the pups for 24 h, resulted in a moderate level of cFos intensity in response to NMA. Total recovery was observed only in animals who had their pups removed for 24 h and the effects of progesterone were blocked. In general, similar results were obtained in the hippocampus except that the total recovery of hippocampal activation took longer than the cortex. Thus, the deficits in cortical activation depend on the presence of both the suckling stimulus and progesterone. However, progesterone alone cannot induce these cortical deficits since pregnant rats showed no deficits in cortical activation in response to NMA when compared to cycling rats. Therefore, the suckling stimulus is required for the inhibition of NMDA-receptor mediated activation of the cortex and hippocampus. The effects of progesterone appear to act synergistically with the effects of suckling. PMID- 8457844 TI - Glucocorticoid prevention of neonatal hypoxic-ischemic damage: role of hyperglycemia and antioxidant enzymes. AB - Recently, we observed that pre-treatment of neonatal rats with dexamethasone prevents brain damage associated with cerebral hypoxia-ischemia (unilateral carotid occlusion + 3 h hypoxia). Presently, we investigate whether hyperglycemia or an induction of endogenous free radical scavengers explains dexamethasone's neuroprotective effect. Pathological damage was examined in rats maintained hyperglycemic during hypoxia-ischemia by the repeated administration of 10% glucose (10 ml/kg, i.p.) at 0, 1, 2 and 3 h of hypoxia (n = 14) and this damage was compared to that in control (n = 15) or dexamethasone (0.1 mg/kg, i.p., n = 15) treated animals. Despite similar elevations in blood glucose at the end of hypoxia, glucose treated animals had greater damage than dexamethasone treated animals and both of these groups had less damage than controls (volumes of damage of approx. 30.9 +/- 10, 3.4 +/- 2.3 and 60.4 +/- 7.1% of the hemisphere, respectively; P < 0.0001). Anti-oxidant enzyme activities were measured within brains of animals treated with dexamethasone or vehicle (n = 44). Activities of the enzymes catalase, glutathione peroxidase and CuZn- or Mn-superoxide dismutase were similar in both treatment groups, with or without exposure to hypoxia ischemia. Thus, an induction of antioxidant enzymes does not explain dexamethasone's effects whereas the relative hyperglycemia associated with glucocorticoid treatment may contribute partially. Neither account fully for dexamethasone's protective effect suggesting an additional glucocorticoid mediated mechanism must be involved. PMID- 8457845 TI - Induction of hippocampal long-term potentiation by alpha-tocopherol. AB - Long-term potentiation (LTP) of synaptic transmission in the hippocampus is thought to be one of the cellular mechanisms underlying learning and memory. Recent evidence in literature suggests the involvement of free radicals in impeding LTP maintenance. In the present study, the effects of alpha-tocopherol, a major lipid-soluble antioxidant which could prevent lipid peroxidation, were examined on the excitatory post-synaptic potentials (EPSPs) of CA1 neurons in guinea pig hippocampal slices. alpha-Tocopherol phosphate disodium salt (0.2 mM applied for 5 min) induced a slowly developing long-lasting increase of the EPSP, without significantly changing the membrane potential, the input resistance and the ability to generate action potentials. No significant changes in the fast and the slow inhibitory post-synaptic potentials (IPSPs) were observed during the alpha-tocopherol-induced LTP of the EPSP. 2-Amino-5-phosphonovalerate (APV) did not block the induction of this LTP. L-Ascorbic acid (Na salt, 3-10 mM), a water soluble antioxidant, failed to produce any significant enhancement in the EPSP. These results indicate that alpha-tocopherol can induce LTP of the EPSP in guinea pig hippocampal CA1 neurons. The activation of N-methyl-D-aspartate (NMDA) receptors does not appear to be necessary for this action of alpha-tocopherol. Whether the LTP-inducing action of this agent is related to its antioxidant property is unclear. PMID- 8457846 TI - Effect of glutamate and its analogs on diacylglycerol and monoacylglycerol lipase activities of neuron-enriched cultures. AB - Neuron-enriched cultures from fetal mouse spinal cord contain diacylglycerol and monoacylglycerol lipases. The treatment of neuron-enriched cultures with glutamate or NMDA resulted in a dose- and time-dependent stimulation in diacylglycerol and monoacylglycerol lipase activities. The elevation in the activities of lipases was blocked by the NMDA receptor antagonists, dextrorphan and MK-801, suggesting that lipase stimulation is a receptor-mediated process. The treatment of neuron-enriched cultures with kainate had no effect on diacylglycerol and monoacylglycerol lipase activities. The stimulation of diacylglycerol and monoacylglycerol lipase activities by glutamate and NMDA suggests that these enzymes may play an important role in processes mediated by the NMDA type of the glutamate receptors. PMID- 8457847 TI - Coupling of cellular energy state and ion homeostasis during recovery following brain ischemia. AB - The present experiments were undertaken to explore the relationship between recovery of cerebral energy state following transient ischemia, and resumption of Na+/K+ transport, as this is reflected in changes in extracellular K+ concentration ([K+]c). Cerebral energy state was evaluated by measurements of cerebral cortical concentrations of phosphocreatine (PCr), ATP, ADP, and AMP at the end of 15 min of severe, incomplete ischemia, as well as after 2 and 5 min of recirculation. Derivation of intracellular pH (pHi) allowed calculation of 'free' ADP (ADPf) and AMP (AMPf) concentrations. Changes in [K+]e were measured by an ion-sensitive microelectrode. The results showed that tissue ATP concentration, which was close to zero after 15 min of ischemia, rose to 30% of control after 2 min, and to 60% of control after 5 min of recirculation. However, since the adenine nucleotide pool was reduced by the ischemia the latter value represents extensive or complete phosphorylation of that pool, as reflected in a normalized ATP/ADPf ratio. During recirculation, the concentration of pyruvate rose, but the lactate content remained unchanged, suggesting that the substrate for oxidative metabolism was exogenous glucose. Resumption of Na+/K+ transport, as reflected in the [K+]e began after 2-3 min, and a normal [K+]e was attained within 5 min. The results demonstrate that transport of Na+ and K+ is resumed at tissue ATP concentrations which are only 30-40% of control. It is discussed whether this reflects relatively extensive rephosphorylation of the remaining adenine nucleotide pool, or if compartmentation of adenine nucleotides exists during recirculation. PMID- 8457848 TI - Effect of chronic ceruletide treatment on dopaminergic neurotransmitters, receptors and their mRNAs in the striatum of rats with dyskinesia induced by iminodipropionitrile. AB - To clarify the mechanism of long-lasting ceruletide action, an analogue of cholecystokinin, in relieving the dyskinesia induced by the iminodipropionitrile (IDPN), we investigated the changes in dopaminergic neuronal system in the striatum. In the control rats, ceruletide had no significant effect on the concentrations of dopamine (DA), DOPAC or HVA or on the turnover of DA in the striatum. The concentration of DA was decreased and the turnover of DA [(DOPAC + HVA)/DA] was increased in the striatum of IDPN-treated rats. Chronic administration of ceruletide (160 micrograms.kg-1.day-1 x 10 days) increased DA concentration and decreased DA turnover only transiently. Both D1 and D2 receptors and their mRNAs were decreased in the striatum of rats given IDPN. After chronic ceruletide treatment, D1 receptor rose to the control level for 3 days, while the D2 receptor rose to a level 1.5 times the control level for 3 days. Even at the 7 days after chronic ceruletide treatment, D2-R rose significantly as compared with the IDPN-treated rats. Both D1 and D2 receptor mRNAs were significantly increased for 3 days in the IDPN-treated rats. These observations indicate that the synthesis of DA receptors is increased by ceruletide treatment in the striatum of IDPN-treated rats. These changes in DA receptors and their mRNAs closely paralleled the changes in dyskinetic movement of the IDPN-treated rats after repeated daily administration of ceruletide, as previously reported. The parallel changes between the DA receptors and dyskinetic movement suggest that an up-regulation of DA receptors in the striatum corresponds with an improvement of dyskinesia in the IDPN-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457849 TI - Role of the vomeronasal system in vasopressinergic modulation of social recognition in rats. AB - To assess the role of the vomeronasal organ (VNO) in the dependence of social recognition on vasopressinergic transmission, vomerectomized rats were compared to intact and castrated male rats. Removal of the VNO significantly decreased the duration of social investigation and temporarily impaired social recognition. In contrast to sham-operated animals and non-operated animals, lesioned rats were no longer responsive to the blocking effect of the antagonist of the vasopressor receptors of vasopressin (dPTyr(Me)AVP, 30 micrograms/kg subcutaneously) on social recognition. Consequently, VNO-lesioned rats behave like castrates, in spite of the lack of effect of removal of the VNO on plasma testosterone levels. These results suggest that androgen-dependent vasopressinergic neurons are part of the VNO pathway and that the VNO system is important for processing and storage of socially relevant information in male rat. PMID- 8457850 TI - Rapid changes in extracellular glucose levels and blood flow in the striatum of the freely moving rat. AB - The dynamics of regional cerebral blood flow and brain extracellular glucose were studied in the freely moving rat. These two variables were measured in the striatum during and following both mild tail pinch and restraint stress. Blood flow was monitored using a refinement of the hydrogen clearance technique that allowed repeated measurements at 5-min intervals. A slow stream of hydrogen was directed at the rat's snout for 10-20 s through lightweight tubing attached to the animal's head and detected at a chronically implanted platinum electrode. Extracellular glucose was monitored with microdialysis in a separate group of animals using an on-line, enzyme-based assay that provided 2.5-min time resolution. Mean striatal blood flow 24 h following implantation was 89.9 +/- 2.5 ml.(100 g)-1.min-1. A 5-min tail pinch caused flow to increase immediately to 169.5 +/- 20 ml.(100 g)-1.min-1. In contrast, there was no change in blood flow during restraint stress, although there was a small increase following the end of the stress. Significant increases in blood flow were also observed in the striatum during periods of eating and grooming. Extracellular glucose levels increased following both forms of stress, to a maximum of 170 +/- 22% of baseline with restraint compared to 110 +/- 2% with tail pinch. In both cases, the increase occurred after the stress had ended and persisted while blood flow returned to basal levels. PMID- 8457851 TI - Effects of postnatal stress on dopamine mesolimbic system responses to aversive experiences in adult life. AB - The effects of postnatal stress on mesolimbic dopamine (DA) functioning in 90-day old mice were investigated. Postnatal stress consisted of 15 min daily exposure to clean bedding (CB) in the absence of the mother for the first two weeks of life. Controls were daily exposed to home cage bedding (HCB) in the absence of the mother. A single brief (5-10 min) exposure to restraint produced a clear-cut increase in DA metabolites (3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 3-methoxytyramine (3-MT)) in the nucleus accumbens septi (NAS) of adult HCB but not CB mice. Moreover, when tested in an elevated plus maze, CB mice showed more exploration and reduced fearfulness in comparison with HCB mice. Taken together, these results indicate reduced emotional reactivity in adult mice repeatedly stressed during postnatal development. Moreover, HCB mice but not CB mice showed altered behavioral responsiveness to apomorphine following repeated restraint stress (10 daily 120 min) in adult life, although no difference in the behavioral response to either a low or a high dose of apomorphine was observed in adult unstressed mice of the CB and HCB groups. These results indicate that the effects of early experiences on brain DA functioning may not be evident in basal conditions and be revealed only under environmental pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457852 TI - Caffeine response in pyramidal neurons freshly dissociated from rat hippocampus. AB - The effect of caffeine on the CA1 pyramidal neurons freshly dissociated from rat hippocampus was investigated with nystatin-perforated patch technique under voltage-clamp condition. Caffeine evoked a transient outward current (Icaffeine) in a concentration-dependent manner at a holding potential of -40 mV. The activation and inactivation of Icaffeine were accelerated with increasing caffeine concentration. The reversal potential for Icaffeine was close to K+ equilibrium potential. The Icaffeine was not blocked by apamin and 4 aminopyridine but suppressed by charybdotoxin, tetraethylammonium, quinine and Ba2+. Thus, the pharmacological characteristics of Icaffeine were similar to those of Ca(2+)-activated K+ current having a large conductance (IC), which generates a fast afterhyperpolarization (a.h.p.). Icaffeine was depressed by pretreatment with a membrane-permeant Ca2+ chelator (BAPTA-AM) and by depletion of the Ca(2+)-induced Ca2+ release (CICR) pool with ryanodine. A blocker of CICR sites, procaine, potently depressed the Icaffeine. In the absence of the extracellular Ca2+, an application of 10 mM caffeine depleted the caffeine sensitive Ca2+ pools. Icaffeine recovered in an exponential fashion in the presence of the extracellular Ca2+. It was concluded that rat hippocampal pyramidal neurons have a caffeine-sensitive Ca2+ pool. Furthermore, the Ca2+ released from the pool evokes K+ current similar to IC current and hyperpolarizes the neurons. PMID- 8457853 TI - The chronic infusion of nicotine into the developing chick embryo does not alter the density of (-)-[3H]nicotine-binding sites or vestibular function. AB - (-)-Nicotine (1.2 mg/day) or saline was infused into chick embryos (Gallus domesticus) for 10 days beginning 12 h beyond the eight day of incubation (E8 + 12 h). Twelve h beyond the eighteenth day of incubation (E18 + 12 h), the eggs were opened to access the embryos and subcutaneous skull electrodes placed. Short latency vestibular response thresholds and input/output functions were determined to assess neurophysiological consequences of chronic nicotine administration. Samples of serum and extraembryonic (amniotic and albumen) fluid were analyzed by gas chromatography-mass spectrometry to determine the levels of nicotine and its major metabolite, cotinine. The brains were removed and divided into diencephalon and mesencephalon and the density of (-)-[3H]nicotine binding sites in each brain area was measured. Nicotine and cotinine were found in the serum and extraembryonic fluid, but nicotinic receptors were not up-regulated in the brains of animals infused with nicotine in comparison to controls. Vestibular response thresholds also did not differ between nicotine-treated and control animals. PMID- 8457854 TI - Hippocampal choline acetyltransferase activity correlates with spatial learning in aged rats. AB - Age-related cognitive deficits in both humans and experimental animals appear to relate to dysfunction of basal forebrain cholinergic neuron systems. The present study assessed spatial learning performance in a water maze task as a function of choline acetyltransferase and high-affinity choline uptake specific activity (the two phenotypic markers for cholinergic neurons) in frontal cortex, hippocampus and striatum of aged male Fischer-344 rats. We observed that increased hippocampal choline acetyltransferase activity was related to better performance on the water maze task, and that, of the individual measures, hippocampal choline acetyltransferase activity was the best predictor of behavioral performance in the spatial learning task. PMID- 8457855 TI - NMDA receptors have a dominant role in population spike-paired pulse facilitation in the dentate gyrus of urethane-anesthetized rats. AB - Paired-pulse facilitation was studied at the perforant path-granule cell synapses in the dentate gyrus of urethane-anesthetized rats. Extracellular field potentials comprising excitatory postsynaptic potentials (EPSPs) and population spikes (PSs) were used to compare facilitation of both responses at interpulse intervals between 10 and 1000 ms. In this model system EPSPs, produced at stimulus intensities well below the PS threshold, exhibited paired-pulse facilitation (PPF) at intervals less than 40 ms. Between 40 and 100 ms both responses were of equal size and from 200 to 1000 ms the second response exhibited paired-pulse depression (PPD). With higher stimulus intensities, PSs exhibited early (10-30 ms) and late (400-1000 ms) PPD and intermediate interval (40-200 ms) PPF. The enhanced PS amplitude during facilitation was accompanied by a modest decrease in EPSP slope and increase in PS latencies to onset and to peak. If PS amplitude was increased to the same extent by simply increasing stimulus intensity, an increase in EPSP slope and decrease in PS latencies to onset and peak were observed. Current source-density analysis revealed that the current sink generated by synaptic activation of granule cell dendrites was indistinguishable between control and facilitated responses up to the onset of the PS. However, the facilitated response exhibited a marked increase in the duration and amplitude of current flowing into the dendrites during the late phase of the EPSP. PPF of the PS was attenuated or blocked by the administration of the known NMDA receptor-ion channel blockers, MK-801, dextromethorphan and ketamine. The depressant effects of these pharmacological agents on facilitation shared the same time course as facilitation itself, peaking at 60 ms and lasting approximately 200 ms. These data suggest that facilitation in this situation is due to postsynaptic rather than presynaptic modulations, and is based upon an increase in the NMDA-mediated component of the evoked response. No increase in transmitter release, per se, could be demonstrated. PMID- 8457856 TI - The central nucleus of the rat amygdala: in vitro intracellular recordings. AB - Membrane properties of neurons from the central nucleus of the rat amygdala (ACe) were analyzed using intracellular current-clamp recordings from in vitro coronal slices of adult rat amygdala. Two types of neurons were identified and classified according to their accommodation characteristics and the nature of their afterhyperpolarizations (AHP). Type A neurons represented 74% of the population and were identified by a lack of accommodation and a medium-AHP (m-AHP) in response to transient (100 ms) depolarizing current injection. The m-AHP was defined by a fast decay time constant with a mean tau AHP = 113.6 ms. In both Type A and Type B ACe cells the m-AHP can be reduced with cadmium and rubidium. Type B neurons represented 26% of the population and were identified by the presence of accommodation and a long duration slow-AHP (s-AHP) following the m AHP. The s-AHP was defined by a slow decay time constant with a mean tau AHP = 1.7 s. The s-AHP was similar to the AHP mediated by IAHP, a long duration calcium dependent, noradrenaline-sensitive current present in hippocampal neurons. In Type B cells, the s-AHP was reduced by cadmium and noradrenaline. There was no significant difference between Type A and B ACe neurons in passive electrical properties such as the membrane input resistance (RiA = 113 M omega, RiB = M omega), and the membrane time constant (tau A = 15 ms, tau B = 16 ms). However, there was a statistically significant difference in the resting membrane potentials of Type A and B ACe neurons (RMPA = -67 mV; RMPB = -63 mV). These data suggest that the characteristic active membrane properties displayed by Type A and Type B neurons will determine the ability of each type to integrate and encode neuronal information. PMID- 8457857 TI - Influence of ZnCl2 pretreatment on behavioral and histological responses to kainic acid in rats. AB - Kainic acid evokes behavioral convulsions and causes lesions in hippocampal pyramidal cell layers in rats. The effects of ZnCl2 pretreatments on these events were examined. Rats were given ZnCl2 (35 mg/kg, subcutaneously (s.c.)) 15 min prior to kainic acid administration (12 mg/kg, intraperitoneally (i.p.)). Another group of animals was given an additional dose of ZnCl2 (35 mg/kg, i.p.) 24 h prior to the s.c. ZnCl2 and i.p. kainic acid. All rats that received kainic acid, whether saline controls or ZnCl2 pretreated, experienced wet dog shakes (WDS) and convulsions. No significant differences were seen between groups in number or latency of WDS or convulsions. Two days after behavioral data were collected, the brains were perfused and the extent of lesioning among hippocampal CA1 and CA3 pyramidal cells was quantified. A single dose of ZnCl2 had either no effect or a slight protective effect on cell lesioning induced by kainic acid. However, lesioning was more pronounced in animals treated twice with zinc. It is concluded that zinc, co-administered with kainic acid, augments kainate cytotoxicity when the dose and timing of zinc exposure are within a critical period. PMID- 8457858 TI - The perifornical area: the major focus of (a) patchily distributed hypothalamic neuropeptide Y-sensitive feeding system(s). AB - Neuropeptide Y (NPY), a neurochemical found in high concentrations within hypothalamic neurons, is believed to participate in the control of eating behavior and body energy balance and elicits a powerful eating response when injected into the hypothalamus. To delineate precisely the locus of this effect, NPY (78 pmol) or its artificial cerebrospinal fluid vehicle was injected in the extremely small volume of 10 nl through chronic guide cannulae into an array of 47 different hypothalamic areas in satiated rats and the elicited food intake was measured. To determine the anatomical resolution of this technique, the spread and recovery of [125I]NPY injected in 10 nl was also assessed. Results indicate that as much as 95% of the injected label was recovered within the brain tissue and guide cannulae and that 100% of the tissue label was localized to within 0.8 mm of the injection site. Behavioral results show that the perifornical hypothalamus (PFH), at the level of the caudal paraventricular nucleus, is the most sensitive hypothalamic site for NPY-induced eating. NPY there elicited mean increases in food intake of 12.5 g over baseline at 1 h and 20.0 g at 4 h postinjection. Injections bracketing the PFH in all directions were substantially less effective. Additionally, significant effects were also observed in at least seven other sites that were distributed throughout the hypothalamus. These findings suggest both that the PFH may be the primary hypothalamic site containing feeding-related NPY-sensitive receptors and that other sites distributed within the hypothalamus also can mediate NPY's effects. PMID- 8457859 TI - Stimulation of the hypothalamic paraventricular nucleus causes systemic venoconstriction. AB - Venous capacitance plays an important role in cardiovascular homeostasis. The anatomical loci within the central nervous system involved in modulating venous function remain to be elucidated. Stimulation of the hypothalamic paraventricular nucleus is known to increase sympathoadrenal outflow and arterial blood pressure. The present study was undertaken to determine whether electrical stimulation of the paraventricular nucleus can also affect the venous circulation. Mean circulatory filling pressure (MCFP) was used as an index of venous tone. Male Long Evans rats were initially anesthetized with pentobarbital (i.p.; 60 mg/kg) and subsequently maintained with urethane (i.v.; 600 mg/kg). Blood pressure and systemic venous pressure were monitored via catheters in the femoral artery and vein and heart rate was derived from the pulsatile blood pressure signal. A latex tipped balloon was placed in the right atrium via the right jugular vein. Mean circulatory filling pressure was calculated from the arterial and venous plateau pressures recorded during five second balloon inflations. Arterial pressure, systemic venous pressure, heart rate and mean circulatory filling pressure were monitored before and during unilateral monopolar electrical stimulation (0.5 ms pulses at 50 Hz for a train duration of 10 s with constant current intensities of 100, 150, 200, and 300 microA) of the paraventricular nucleus. Increased graded stimulation of the paraventricular nucleus increased blood pressure by 6 +/- 2, 8 +/- 1, 13 +/- 2 and 26 +/- 5 mm Hg while heart rate changed by -22 +/- 6, -18 +/- 6 and -15 +/- 9 bpm and +10 +/- 10 bpm, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457860 TI - Two distinct unit activity responses to morphine in the rostral ventromedial medulla of awake rats. AB - Past research investigating the rostral ventromedial medulla (RVM) in anesthetized animals has found two distinct classes of cells, ON and OFF, noted for their distinct responses to noxious stimuli and to morphine. However, only one class (ON) has been found in the awake animal paradigm. We report in this paper that we have found both the ON and OFF cell responses to morphine in the awake rat. PMID- 8457861 TI - Effects of aging on NMDA and MK801 binding sites in mice. AB - [3H]MK801 binding was significantly reduced in three cortical and two subcortical regions in 30-month-old C57Bl mice, as compared to 3-month-olds. NMDA binding sites showed significant reductions with aging in sixteen of nineteen brain regions. These results suggest that, in a majority of cortical and hippocampal regions, decreases in binding to NMDA sites with aging may be due to factors other than cell loss. PMID- 8457862 TI - Cholecystokinin receptor density in the striatum of the spontaneously hypertensive rat. AB - The possibility that cholecystokinin in the striatum may be involved in hypertension was investigated using in vitro receptor autoradiography. The binding density of 125I-Bolton Hunter labeled cholecystokinin octapeptide (125I BH-CCK8) was determined using computer-assisted densitometry in the striatum of the spontaneously hypertensive rat (SHR) and its control the Wistar-Kyoto rat (WKY). A significant increase in 125I-BH-CCK8 binding density was found in the lateral part of the caudate-putamen of the SHR. In contrast, a significant decrease in 125I-BH-CCK8 binding density was found in the posteromedial nucleus accumbens of the SHR. These results indicate that CCK8 receptor density is altered in the striatum of the SHR and suggest a role for CCK8 receptors in the pathophysiology of hypertension. PMID- 8457863 TI - Quantitative electromyographic changes following modification of central dopaminergic transmission. AB - Muscle tone was assessed by measurement of quantitative electromyographic (EMG) activity recorded from electrodes chronically implanted in the gastrocnemius and anterior tibialis muscles of conscious, unrestrained rats. Following treatment with reserpine or denervation with 6-hydroxydopamine a significant increase in EMG activity of both muscles was observed, confirming the utility of the method for studying the effects of changes in central dopaminergic transmission on muscle tone. PMID- 8457864 TI - Comparison of the effects of voltage-sensitive calcium channel antagonism on the electrically stimulated release of dopamine and norepinephrine in vivo. AB - IN vivo electrochemistry was used to monitor the effects of several voltage sensitive calcium channel (VSCC) antagonists (e.g. divalent metal ions, diltiazem and omega-conotoxin GVIA (omega-CT) on the electrically evoked release of dopamine (DA) in the striatum and norepinephrine (NE) in the thalamus of the anesthetized rat. The results suggest that the N-type voltage-sensitive calcium channel is the primary VSCC involved in the electrically stimulated release of DA in the striatum, whereas stimulated release of NE in the thalamus was only partially dependent on N-type VSCC. In addition, DA release appears to be more sensitive to VSCC antagonism than does NE release with the in vivo application used in this study. PMID- 8457865 TI - Increase in number of LHRH neurones in septal-preoptic area of rats following chronic amitriptyline treatment: implication in antidepressant effect. AB - Recent studies have implicated the peptide LHRH in a variety of actions including a role in modulation of affective behavior. The present study has been undertaken to determine its involvement in the action of antidepressants, if any, using amitriptyline (AMT) as the model antidepressant drug. The repeated administration of AMT (10 mg/kg/day) in rats increased the number of LHRH neurones in the septal preoptic area. While 1 week of AMT treatment slightly augmented the number of LHRH neurones, the rise was not statistically significant, however, following 2 weeks of AMT treatment, a significant (P < 0.05) increase (41.05%) was observed. Three and four weeks of AMT treatment further increased the number of neurones by 60.84% and 72.96% respectively; a remarkable rise in the LHRH immunoreactivity around organum vasculosum of lamina terminalis (OVLT) was also noticed. Acute AMT treatment had no effect on the number of neurons; however, the intensity of immunoreaction in the OVLT was slightly decreased. In the behavior despair test, a single dose of AMT displayed an immobility reducing effect which was also shown by a single dose of LHRH (1 mg/kg). The combination of LHRH (1 mg/kg) and AMT also reduced the immobility; the effect was the same as one produced by each drug given separately. The results suggest that chronic AMT treatment may induce transcription and translation in LHRH cells and that the peptide LHRH may be involved in the mediation of the antidepressant effect, characteristic of AMT. PMID- 8457866 TI - Study of the stereoselectivity of L-glutamate receptors by synthetic 4(R)- and 4(S)-substituted L-glutamate analogues. AB - R- and S-stereoisomers of 4-substituted L-glutamate analogues are used to study the stereoselectivity of L-glutamate receptors. It is found that 4(R)-substituted analogues are more potent than their 4(S)-isomers in interacting with L-glutamate receptors both at porcine brain synaptic junctions and on drosophila muscles. This demonstrates that the ligand recognition site of L-glutamate receptors has chiral selectivity discriminating L-glutamate analogues with bulky 4(R)- and 4(S) substituent groups. PMID- 8457867 TI - Development, plasticity, and regeneration in the spinal cord: cellular and molecular interactions. Satellite symposium of the 3rd IBRO World Congress of Neuroscience. August 11-14, 1991, Quebec, Canada. PMID- 8457868 TI - Projection patterns of primary sensory neurons studied by transganglionic methods: somatotopy and target-related organization. AB - The anatomical organization of the centrally projecting branches of different peripheral sensory nerves was not possible to investigate efficiently until the development of the axonal tracing methods. Horseradish peroxidase applied peripherally could be visualized in central projection areas provided a sensitive histochemical method was used; this created the basis for transganglionic tracing from the periphery. This has permitted the investigation of large-scale projections from peripheral sensory nerves. The use of conjugates of horseradish peroxidase and lectins with affinities for different populations of primary sensory neurons, as well as the use of different postoperative survival times, has offered the possibility for selective visualization of projections from subsets of primary sensory neurons. For detailed studies of single afferent fiber projections, a combined physiological-anatomical approach using single-unit recording followed by intraaxonal application of horseradish peroxidase, has become the method of choice. This chapter will focus on results which have been achieved by transganglionic tracing methods, in regard to the organization of the central projections of peripheral sensory nerves. PMID- 8457869 TI - Tooth pulp primary neurons: cell size analysis, central connection, and carbonic anhydrase activity. AB - Cell bodies and central terminals of trigeminal primary afferent neurons innervating the mandibular molar and incisor tooth pulps were labeled by injecting various neuroanatomical tracers into these tooth pulps. The cell bodies of major constituents of primary neurons innervating the tooth pulp, cornea, and cutaneous branch of the mylohyoid nerve were large (> or = 500 microns2, 65%), medium (300-400 microns2, 35%), and small (100-200 microns2, 34%), respectively. Those innervating the tooth pulp (tooth pulp cells) had the Nissl pattern characteristic of large light cells of the A type, while those innervating the cornea were small dark cells of the B type. Thirty percent of the tooth pulp cells exhibited histochemically demonstrable carbonic anhydrase activity. The transganglionic transport of HRP-WGA indicated marked concentration of central terminals of the tooth pulp primaries in the rostral subdivisions of the brain stem sensory trigeminal nuclear complex. In contrast, central terminals of the corneal primaries were concentrated in the medullary dorsal horn. PMID- 8457870 TI - Expression of dopamine by chick primary sensory neurons and their related targets. AB - The expression of dopamine by primary sensory neurons and their peripheral projections was studied in the chick dorsal root ganglion by means of immunocytochemical procedures. Within the sensory neurons, dopamine immunoreactivity is first expressed by 0.8% of cells at E10 and reaches a percentage of 5.6% before hatching. After hatching, 8.6% of neurons, belonging to both the A and B classes of sensory neurons, exhibit a clear immunostaining. According to the immunostaining of nerve terminals located in various peripheral target tissues, these immunoreactive neurons are responsible, at least in part, for the sensory innervation of the skin and paravertebral ganglia. The results provide evidence that different classic neurotransmitters may be expressed by specific subpopulations of primary sensory neurons expressing various somatic and autonomic sensory functions in relation to specific targets. PMID- 8457871 TI - Plasticity of developing and adult dorsal root ganglion neurons as revealed in vitro. AB - We review recent data on the plasticity of dorsal root ganglion (DRG) neurons as revealed during cultivation in vitro. Some experiments on cultured developing DRG neurons and on adult DRG neurons in vivo are also mentioned. Cultured developing and adult DRG neurons can be switched from an apolar to a multipolar phenotype by fetal calf serum or fibronectin. The effect is concentration dependent and occurs through an early modification of cell-substratum interaction. Adult DRG neurons synthesize and release within hours after injury TGF beta-1, which is a mitogen and a differentiation factor for Schwann cells. Finally, adult DRG neurons express in vitro neurotransmitters that are not expressed in vivo. This neurotransmitter plasticity can be modulated in vitro by some growth factors and in vivo by distal or proximal axotomy. PMID- 8457872 TI - Regulation of myelinated nociceptor function by nerve growth factor in neonatal and adult rats. AB - The role of nerve growth factor (NGF) as a survival factor for sensory neurons during embryonic life has been well documented. Here we examine the actions of NGF or antisera against NGF (anti-NGF) on physiologically identified sensory neurons with myelinated axons later in life, after the dependence on NGF for survival ends. We find that the effects of NGF and anti-NGF are specific for sensory neurons which are nociceptors. Treatments were found to affect the biophysical properties, the development, or the physiological function of myelinated nociceptors. They also affect the animal's behavioral response to noxious stimulation, depending upon when the treatments were given: neonatally, from 2-5 weeks of age, or chronically, beginning at birth. Thus, we find that the actions of NGF are specific for nociceptors but that the function of this neurotrophic factor changes according to the developmental age of the animal. PMID- 8457873 TI - Migration of crest-derived cells from gut: gut influence on spinal cord development. AB - The technique of backtransplantation was used to investigate the developmental potential of neural crest cells that have migrated to and colonized the bowel. Segments of chimaeric gut in which only the crest-derived cells were of quail origin, were grafted between somites and neural tube of younger chick host either at truncal (somites 18-24) or at rhombencephalic level. Quail neural crest derived cells were identified in the spinal cord, spinal roots and ganglia, sympathetic ganglia and the adrenals, cranial sensory ganglia according to the level selected for the graft. These experiments demonstrate that crest-derived cells, having previously migrated to the gut, retained the ability to migrate to distant sites into a younger host. The chimaeric gut transplants induced a unilateral increase in the host's neural tube as it had been previously revealed after quail gut, skeletal, and cardiac muscle backtransplantation. Moreover, our experiments demonstrate that the number of the motor neuron progenitors is affected when spinal cord and gut experimentally developed in close contact. These observations support the hypothesis that gut smooth muscle as striated muscles releases a short range diffusible factor that induces proliferative effects on the neuroepithelial cells. The growth-promoting effect occurs during the time neurons are actively generated. It must still be determined whether such extrinsically derived factors participate in the regulation of cell proliferation in the central nervous system. PMID- 8457874 TI - Differentiation of neurogenic precursors within the neural crest cell lineage. AB - It has been suggested that many, if not all crest-derived neurons develop from a limited subpopulation of neurogenic precursors. To develop cell-type specific markers that identify these precursors directly we have used differential screening of crest-derived cell populations known to have, or not to have, neurogenic ability. We have determined that the neuron-specific human auto antibodies designated Anti-Hu bind to cytoplasmic and nuclear determinants not only in mature avian neurons and neuroendocrine cells but also in subpopulations of morphologically non-neuronal avian crest-derived cells. Significantly, these Anti-Hu+ non-neuronal crest-derived cells are present only in populations that have neurogenic ability and are absent from populations that lack neurogenic ability. Moreover, following additional development in vivo or in vitro, Anti-Hu+ non-neuronal crest-derived cells appear to express other neuronal traits. These results suggest that Anti-Hu-immunoreactivity is an early indicator of neurogenesis among crest-derived cells, and that Anti-Hu+ non-neuronal cells are either neurogenic precursors or immature neurons. Similarly, using the same differential screening paradigm, we have identified two monoclonal antibodies, designated 12E10 and 17F5, which also label both neurons and some apparently nonneuronal cells in neurogenic populations of neural crest cells. Anti-Hu-IR appears to precede expression of either of these two markers. PMID- 8457875 TI - The development of brain stem projections to the spinal cord in the chicken embryo. AB - Recent studies of the development of brain stem projections to the spinal cord in the chicken embryo, with an emphasis on axon pathway selection, are reviewed. Neurons from medullary to mesencephalic levels project to the spinal cord along specific fiber tracts. Coherent, segregated neuron groups can be defined on the basis of which tract and which side of the brain stem they project on. The choice of axon trajectory is, therefore, correlated with neuron position. During development, these trajectory-defined brain stem groups project to the spinal cord in a stereotyped sequence. Early stages of this sequence reveal a potential homology between the reticulospinal systems of avians and lower vertebrates. The possibility that neuron position may be involved in determining axon pathway choice of brain stem projections is supported by complementary studies on vestibuloocular projections. The boundaries between vestibuloocular, vestibulospinal, and reticulospinal neuron groups coincide with rhombomere boundaries and boundaries between longitudinal cell columns. Axon trajectory specific domains are, therefore, correlated with segmental and mediolateral patterns of differential gene expression. PMID- 8457876 TI - The disposition of early-generated neurons in the rat embryo predicts the pattern of major axonal tracts. AB - During embryogenesis, the fiber tracts grow in a highly stereotyped pattern. A very small number of predetermined paths, preceding the growth of fasciculi, are present in the young neural tube (10-12, 15). What is the origin of these substrate pathways defined by Katz et al. (16) as "... a set of similar guidance cues which are aligned in a continuous discrete pathway..."? Could the first neurons play a role in the guidance of early nerve fibers? Observations in the brain stem revealed the presence of two longitudinal columns of early-generated neurons. These longitudinal columns were associated with well-differentiated marginal zones, characterized by cell-free spaces and representing the prospective site of the medial longitudinal (mlf) and lateral longitudinal (llt) tracts. Nerve fibers were also traced in the brain stem of young embryos. Axons were seen to travel in the early mlf and llt, in close proximity to the regions of early-generated neuronal columns. The data suggest that the precocious neurons that are organized in a definite pattern could somehow be involved in the guidance of some longitudinal axonal tracts, either by directly promoting the formation of an adequate terrain in the marginal layer, or by inducing other cells to do so. PMID- 8457877 TI - Ontogenetic study of early brain stem projections to the spinal cord in the rat. AB - In an attempts to describe the early development of the brain stem-spinal projections, we implanted DiI crystals at the C3 level of the spinal cord of 13- and 14-day fixed embryos. After a diffusion period of 2 to 4 months, neurons of the rhombencephalic reticular formation were retrogradely labeled by the tracer. This group of neurons was situated ventromedially in the tegmentum. Their axons coursed into the ventral marginal layer at bulbar levels and entered the ventral funiculus when reaching the spinal cord. Neurons of the lateral vestibular nucleus were also labeled and gave rise to descending fibers that gradually moved medially and entered the spinal cord in the ventral funiculus. In the mesencephalon, labeled cell bodies of the interstitial nucleus of Cajal (InC) were found lying ventrally in the tegmentum, at the rostral end of the medial longitudinal fasciculus (mlf), in which their axons coursed. Also, in the midbrain, several cells lying dorsal to the InC, with axons descending in the lateral tegmentum, were tentatively identified as part of the mesencephalic reticular formation. PMID- 8457878 TI - The ontogenic development of sensorimotor reflexes and spontaneous locomotion in the Mongolian gerbil (Meriones unguiculatus). AB - Most behavioral studies on the ontogeny of sensorimotor reflexes and locomotion were done in quadrupedal species with equally developed forelimbs (FL) and hindlimbs (HL). In contrast, the Mongolian gerbil has long and strong HL but relatively small FL, indicating their differential use for locomotion. We have used the gerbil to study the ontogeny of a number of reflexes and locomotor acts to see if their sequence of appearance, their maturation, as well as their intensity of expression, differed from some other mammals. The following sequence was observed: forward FL hopping, FL grasp, forward HL hopping, surface body righting, chin tactile placing, lateral FL hopping, lateral HL hopping, medial FL hopping, medial HL hopping, visual placing, air body righting, and FL and HL tactile placing. When comparing FL and HL, a given reflex does not necessarily appear earlier in the limb that expresses it more strongly. The results are discussed in relation to the development of the central nervous system, the limb, and the locomotor behavior. PMID- 8457879 TI - The origins of descending projections to the lumbar spinal cord at different stages of development in the North American opossum. AB - We have employed the retrograde transport of fast blue (FB) to identify the origins of descending projections to the lumbar cord of the opossum from postnatal day (PD)1, 12-13 days after conception, to maturity. When FB injections were made into the lumbar cord at PD1, supraspinal labeling was sparse and limited to the hypothalamus, the reticular formation, the coeruleus complex, the caudal raphe, and, in one case, the interstitial nucleus of the medial longitudinal fasciculus and the lateral vestibular nucleus. Only a few propriospinal neurons were labeled at cervical and thoracic levels. By PD3, however, supraspinal and propriospinal labeling was abundant and present in most of the areas labeled in the adult animal. A notable exception was the red nucleus which was not labeled until approximately PD10. Our results have been compared with those described in other species and discussed in light of their relevance to the development of descending control over hindlimb movement and developmental plasticity of descending spinal pathways. PMID- 8457880 TI - Dorsal and ventral dopaminergic innervation of the spinal cord: functional implications. AB - Several studies have demonstrated that a descending dopaminergic pathway innervates the dorsal and the intermediate gray matter of the spinal cord and have suggested that this pathway is involved in pain modulation and in the control of autonomic functions. Other studies have also demonstrated the presence of dopamine (DA) and DA metabolites as well as of DA receptors in the ventral cord. There is also evidence for the implication of DA in the control of motor functions at the spinal level. The occurrence of a dopaminergic innervation in the ventral horn has been, however, disputed until recently. But recent work has demonstrated that the motoneural cell groups in the ventral horn (lamina IX) are a target for descending dopaminergic fibers. In addition, the possibility that DA is a mediator of primary afferent fibers has also been postulated. Finally, the occurrence of dopaminergic cell bodies has been suggested in the spinal cord. This indicates that DA is probably implicated in a complex manner in spinal functions. In the present paper the possible involvement of DA in sensory and in motor functions at spinal level will be discussed in view of neurochemical observations made in polyarthritic rats, in which pain-related behavior and reduction of locomotor activity associated with a marked decrease in mobility, are observed. PMID- 8457881 TI - Expression of gamma-aminobutyric acid and calcium binding protein-parvalbumin by chick motoneurons. AB - The expression of calcium binding protein parvalbumin (PV) and gamma-aminobutyric acid (GABA) was studied in the chick motoneurons by using pre- and postembedding immunocytochemistry. Our data reveal that PV and GABA are colocalized in the majority, but not all, of chick lumbo-sacral spinal motoneurons innervating the somatic muscles. It is suggested that, in this neuromuscular system, GABA does not act as a classical inhibitory neurotransmitter but, combined with calcium, could be involved, at least in part, in the maintenance of neurons and the prevention of cell death as in certain neurodegenerative disorders. PMID- 8457882 TI - Schwann cell induction in the ventral portion of the spinal cord. AB - Schwann cell development can be induced in a predictable manner in the dorsal aspect of the lumbosacral spinal cord of the immature rat by exposing that structure to ionizing radiation. This development occurs in essentially all animals and becomes evident between 2 and 3 weeks postirradiation (P-I). Occasionally, intraspinal Schwann cells were observed ventrally at later intervals following irradiation, usually more than 45 days P-I. The present study focused on the development of Schwann cells within the ventral portion of the lumbosacral spinal cord in 53 animals followed for periods up to 7 months P-I. Ventrally located intraspinal Schwann cells developed in approximately 40% of these animals, in contrast to the development dorsally in all animals. The ventrally located aggregates were generally smaller than those dorsally and occurred more frequently in gray matter than in white matter. An interesting feature of the ventrally located Schwann cells was that they were often associated with blood vessels, which raised the possibility that these cells developed from undifferentiated cells of the vascular walls or used the vessels as a pathway for migration. PMID- 8457883 TI - Potential regulation by trophic factors of low-affinity NGF receptors in spinal motor neurons. AB - Developing spinal motor neurons (SMN) express low-affinity nerve growth factor receptors (LNGFR) but not high-affinity transducing NGF receptors. Moreover, SMN are not supported by NGF in vitro. In the normal adult rat most SMN are not LNGFR immunoreactive (LNGFR-IR), but they transiently reexpress LNGFR (though not the high-affinity receptor) after peripheral nerve injury. With a cut lesion of the sciatic nerve (when only a neuroma forms), the number of LNGFR-IR SMN at L4-L6 rapidly increases to a maximum between day 1 and 7 and returns to baseline levels by day 30. After a crush lesion (accompanied by regeneration to the muscle), LNGFR-IR SMN appear in about the same numbers, but they start to disappear 1 week later. We speculate that the similar appearance and differential decline of LNGFR IR seen after the two types of lesions are regulated by the availability of a common signal such as ciliary neurotrophic factor. The adult SMN model provides a good opportunity to investigate the reexpression of LNGFR after peripheral nerve injury, and more generally, the unknown role and regulation of LNGFR. PMID- 8457884 TI - Clinicopathological features of primary lateral sclerosis are different from amyotrophic lateral sclerosis. AB - Primary lateral sclerosis (PLS) bears close resemblance to cases of amyotrophic lateral sclerosis (ALS) presenting with spasticity, but histopathological studies have shown significant difference between the two conditions. When the lower motor neurons in cases of ALS and PLS are compared with the equivalent cells of control subjects, morphometric studies indicate significantly decreased size and increased convexity (rounding) of the cell bodies only in ALS. In both disorders there is loss or shrinkage of the largest cortical motor neurons (Betz cells) in the primary motor cortex, though this change is not conspicuous in all cases of ALS. Morphometry reveals in both diseases a general reduction in the sizes of pyramidal cells in the precentral gyrus, indicating that smaller neurons are involved. The cortical motor neurons shrink more in PLS than in ALS. It is concluded that there is clear difference between ALS and PLS. In PLS, quantitative histopathological data show that the neuronal degeneration is confined to long descending pathways, notably the corticospinal system, with no concomitant involvement of lower motor neurons. In ALS, lower motor neuron degeneration occurs in all cases, whereas involvement of the motor cortex is variable. PMID- 8457885 TI - Selective vulnerability of alpha motor neurons in ALS: relation to autoantibodies toward acetylcholinesterase (AChE) in ALS patients. AB - The degenerative process in amyotrophic lateral sclerosis (ALS) concerns primarily alpha motor neurons in the spinal cord and brain stem, and neurons forming descending pathways to the cord, especially in the pyramidal tract. Some degeneration of large peripheral sensory nerve fibers often occurs too, but preganglionic autonomic neurons and gamma motor neurons are most often spared in the disease. The vulnerability of alpha motor neurons compared to other types of neurons in ALS is discussed in relation to retrograde axoplasmic transport from peripheral blood of foreign noxious macromolecules, interneuronal transport of such molecules, and neuronal surface structure properties relevant to uptake for retrograde axoplasmic transport. Certain differences in these aspects between alpha motor neurons and other neuronal types exist. Some differences concern the neuronal turnover of acetylcholinesterase (AChE), which could be of special interest in view of the recent demonstration of regular occurrence of autoantibodies towards this enzyme in ALS patients. PMID- 8457886 TI - Experimental immune-mediated motor neuron diseases: models for human ALS. AB - Amyotrophic lateral sclerosis is an idiopathic, ultimately fatal disease, clinically manifest as progressive weakness and spasticity, associated with the loss of motoneurons. Circumstantial evidence supports a role for autoimmune processes in the progression of this human disorder. Two immune-mediated animal models have been developed in our laboratory for motor neuron loss. Experimental autoimmune motor neuron disease is a lower motor syndrome induced in guinea pigs by the repeated injection of a purified bovine spinal motor neuron antigen. Affected animals demonstrate extremity weakness, associated with electromyographic and morphologic evidence of denervation, a loss of spinal cord motor neurons, high antibody titers against motor neurons, and localization of IgG immunoreactivity to the neuromuscular junction and motor neuron cytoplasm. Experimental autoimmune grey matter disease is a more acute and severe disorder involving both upper and lower motor neurons, induced in guinea pigs by inoculation of a bovine ventral spinal cord homogenate, in which scattered foci of denervation are observed in the motor cortex and ventral spinal cord. Similarities between these diseases and human ALS are reviewed. PMID- 8457887 TI - Altered metabolism of excitatory amino acids, N-acetyl-aspartate and N-acetyl aspartyl-glutamate in amyotrophic lateral sclerosis. AB - Since recent studies provided evidence for abnormal glutamate metabolism in amyotrophic lateral sclerosis, we measured amino acid levels in the fasting plasma of 52 ALS patients and an equal number of controls of a similar age. In addition, the content of amino acids, N-acetyl-aspartate (NAA) and N-acetyl aspartyl-glutamate (NAAG) were measured in spinal cord and brain tissue obtained at autopsy from patients dying of ALS. Results showed significant elevations (by about 70%) in the plasma levels of glutamate in the ALS patients as compared to controls. In contrast, glutamate levels were significantly decreased in all CNS regions studied of ALS patients (by 21-40%), with the greatest changes occurring in the spinal cord. The ratio of glutamine to glutamate was altered significantly in the spinal cord ALS tissue. In addition, reductions in the levels of aspartate (by 32-35%), NAA, and NAAG (by 40-48%) were found in the spinal cord of ALS patients. These results are consistent with a generalized defect in the metabolism of neuroexcitotoxic amino acids. An altered distribution of these compounds may occur between their intracellular and extracellular pools with resultant abnormal potentiation of excitatory transmission mediated by glutamate receptors and selective degeneration of motor neurons. PMID- 8457888 TI - Noradrenergic agonists and locomotor training affect locomotor recovery after cord transection in adult cats. AB - In one series of experiments, the effects of noradrenergic, serotonergic, and dopaminergic precursors and agonists on the initiation of locomotion were investigated within the first week after complete spinalization at +13 in five adult cats. In addition, the effects of clonidine and daily locomotor training were investigated during the first week after transection in another cat. The electromyographic (EMG) activity of vastus lateralis (VL) and semitendinosus (St) was recorded bilaterally through percutaneously implanted copper wires in all cats. The movement of the hindlimbs on the treadmill was also simultaneously videorecorded before and after the injection of drugs. Without drug injection, strong and sustained perineal or abdominal stimulation did not induce any prolonged episodes of coordinated stepping on the treadmill during the first week after spinalization. St often had sustained activity, in contrast to VL, in which minimal or no activity was present. Injection of apomorphine (0.3 to 0.5 mg/kg, n = 3), a dopaminergic agonist, or DL-5-HTP (50 mg/kg, n = 2), a serotonergic precursor, failed to induce locomotion at such an early stage after spinalization. In contrast, injection of either L-dopa (50-60 mg/kg, n = 2), a noradrenergic precursor, or clonidine (150 micrograms/kg, n = 2), a noradrenergic agonist, induced locomotion on the treadmill. The animal demonstrated bilateral foot placement on the soles and complete weight support of the hindquarters. The spinal cat could follow the treadmill speed up to 0.80 ms-1. However, these effects disappeared when the NA drugs were tapered off.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457889 TI - Diversity among reactive astrocytes: proximal reactive astrocytes in lacerated spinal cord preferentially react with monoclonal antibody J1-31. AB - An Astrocyte-specific antigen recognized by monoclonal antibody J1-31 is a more intense marker for proximal reactive astrocytes in lacerated rat spinal cord than is glial fibrillary acidic protein (GFAP). Thus, MAb J1-31 recognizes reactive astrocytes in the immediate vicinity of the lesion, whereas reactive astrocytes that are located at a distance from the lesion are not detected by immunofluorescent staining. These findings are relevant to the biochemical heterogeneity manifested respectively by reactive astrocytes located proximal and distal to a laceration-type injury of the spinal cord, and those that develop following axotomy with retrograde degeneration. Reactive astrocytes in the axotomy model are not stained with MAb J1-31, but are positive for GFAP. PMID- 8457890 TI - Regrowth of motor axons following spinal cord lesions: distribution of laminin and collagen in the CNS scar tissue. AB - In previous studies we have demonstrated that spinal motoneurons in the adult cat can regenerate CNS-type axons through CNS scar tissue into denervated ventral roots. This scar tissue, which appears to support and sustain the growth of injured CNS axons, has been shown to have a persistent defect in the blood-brain barrier (BBB). In the present study, the binding of antibodies to nerve growth factor receptor (NGFr), laminin, collagen, and a microtubule associated protein (MAP5) was assessed with indirect immunohistochemical methods 4 days-20 weeks after a lesion in the ventral funiculus of the spinal cord. An increase in content of collagen-, laminin-, and NGFr-like immunoreactivity was observed in the scar tissue during the first 3 weeks. Although type I collagen dominated in superficial areas of the scar, type IV collagen and laminin-like immunoreactivity was observed in expanded perivascular spaces all over the lesion zone. Type IV collagen- and laminin-immunoreactive structures sometimes appeared to form strands which interconnected the ventral horn and the ventral root. Regenerating axons, as revealed by staining with MAP5 or NGFr antibodies, were observed in close association to these paths. It has been suggested that a breakdown of the BBB may play a vital role in certain types of CNS regeneration by increasing the access of blood-borne trophic factors to the lesion area. The demonstration of extracellular matrix proteins like laminin provides further evidence for the notion that the observed regenerative growth takes place in an environment that is markedly different from the normal CNS. PMID- 8457891 TI - Evaluation of two cross-linked collagen gels implanted in the transected spinal cord. AB - In previous experiments, we have shown that spinal axons grow into a collagen matrix implanted between the stumps of a transected spinal cord. However, the matrix became denatured after 2 to 3 months. To improve the stability and the durability of the collagen gel implants, collagen was coprecipitated with chondroitin-6-sulfate (C-6-S) or chemically cross-linked with carbodiimide (CD). The spinal cords were taken out after 3 days, 1, 3, or 6 months and analyzed using different histological and tracing techniques. The cross-linked collagen matrices underwent major structural changes. Cross-linking treatments improved the stability of collagen implants which withstood at least 6 months. Axons revealed with DiI or silver staining crossed the proximal interface and grew into the bioimplants. Some axons were also followed across the distal bioimplant spinal interface in DiI treated tissues. This study suggests that cross-linking the collagen hydrogel has improved the mechanical properties of the matrix, modified the normal scarring process, and favored axonal regeneration. PMID- 8457892 TI - Synthetic polymer derivatives as substrata for neuronal adhesion and growth. AB - The adhesion and viability of dissociated neurons of rat cerebral hemispheres onto methacrylate and methacrylamide hydrogels, either unmodified or containing collagen, basement membrane proteins, and glucosamine, were measured in vitro. The degree of cell adhesion was affected by properties of the polymers such as hydrophilicity, hydrophobicity, presence of reactive chemical groups, and incorporation of biological molecules. Adhesion was promoted by attachment of glucosamine to the polymer backbone. Viability was enhanced by the presence of basement membrane proteins within the polymer network. Morphological studies of cells seeded, both onto and within the polymeric matrices, demonstrated the capacity of such substrates to support neuritic outgrowth. The potential of these in vitro assays in the design of polymeric matrices as neural tissue repair promoter substrate is discussed. PMID- 8457893 TI - Regeneration of lesioned cholinergic septal neurons of the adult rat can be promoted by peripheral nerve grafts and a fibrin-fibronectin-containing matrix of peripheral regeneration chambers. AB - Axonal regeneration of septal cholinergic neurons was examined after lesion of the septohippocampal pathway of the adult rat and implantation of tubes containing peripheral cellular or acellular substrates. After empty tube implantation, no regenerated structures were observed in the conduit. However, after implanting tubes filled with sections of predegenerated sciatic nerves or a fibrin-fibronectin-containing matrix provided by peripheral regeneration chambers, numerous regenerated axons were detected 6 weeks after the operation. At the electron microscopic level, regenerated axons were observed in the grafted sciatic nerves in contact with Schwann cells but also in contact with astrocytes which were able to migrate and send processes into the graft. After fibrin fibronectin-containing-matrix implantation, the regenerated structure between septum and hippocampus was composed mainly of fibroblasts, astrocytes, and regenerated axons associated to these central glial cells. PMID- 8457894 TI - Novel surgical strategies to correct neural deficits following experimental spinal nerve root lesions. AB - In attempts to correct neural deficits following avulsion trauma, novel experimental strategies were developed. In rats, spinal roots were replanted superficially in the dorsal horn following dorsal root avulsion and concomitant denervation by ganglionectomy. Outgrowth from cord neurons in the dorsal horn into the implanted dorsal root was demonstrated by means of retrograde HRP labeling. Double labeling experiments showed that some of these neurons had retained their central projections while extending new processes into the implanted root. After dorsal root avulsion, sensory pathways might be reconstructed by substituting the lost input from damaged primary sensory neurons with induced peripheral outgrowths from secondary neurons. In primates, intraspinal replantation of avulsed ventral nerve roots was investigated as a surgical treatment for motor deficits that develop after severe brachial plexus injury. Two to 3 months after surgery there were EMG signs of reinnervation in previously denervated muscles, which were shortly followed by evidence of clinical recovery. A gradual improvement in the function of the affected arm occurred and motor behavior became normalized, although the EMG activity in the reinnervated muscles at maximal contraction was still reduced. The outcome of these experimental studies indicates that reconstructive surgery applied to the brachial plexus might be of value to restore functional deficits induced by traumatic spinal nerve root avulsions also in man. PMID- 8457895 TI - Regenerative neurite growth modulation associated with astrocyte proteoglycans. AB - Adherent GFAP-positive cells of neocortical origin in vitro produce and release members of three families of sulphated proteoglycans and a sulphated protein that copurifies with heparan sulphate proteoglycan (HSPG). Conditioned medium (CM) and the proteoglycans contained in the CM have neurite growth-promoting activity when immobilized on defined substrates of growth but not when in the nonimmobilized compartment. On a poly-D-lysine substrate, the rank ordering of specific neurite growth activity based on protein concentration was 330 kDa HSPG >> 100 kDa HSPG/chondroitin sulphate (CS) PG mixture or hybrid > 330 kDa CSPG > 50 kDa CSPG/dermatan sulphate (DS) PG mixture or hybrid and the 31 kDa sulphoprotein. Astrocyte CM lost its growth facilitatory activity when prepared and released by astrocytes in the presence of soluble mediators of inflammation. Loss of activity could not be explained by qualitative or quantitative alterations of released proteoglycans but appeared to be associated with the presence of an inhibitor. The sulphoprotein that copurified with HSPG was a potent inhibitor of HSPG mediated neurite growth. PMID- 8457896 TI - Immature corticospinal neurons respond to axotomy with changes in tubulin gene expression. AB - We have examined the expression of two different tubulin mRNAs in hamster corticospinal neurons that were axotomized at three different developmental stages; postnatal day 8 (P8), P20, and adult. In situ hybridization of histological sections of the sensorimotor cortex was done with 35S-labeled cDNA probes specific to alpha 1-tubulin and beta III-tubulin mRNAs at 2-14 days following unilateral transection of the corticospinal tract in the caudal medulla. Both film and emulsion autoradiography were used to detect changes in tubulin mRNA levels. Qualitative assessment indicated substantial decreases in both alpha 1-tubulin and beta III-tubulin mRNA levels in layer V neurons of the sensorimotor cortex following axotomy. The changes were apparent as early as 2 days postinjury for P20 and adult operates, but not for P8 operates. However, by 14 days postinjury, decreases in alpha 1-tubulin and beta III-tubulin gene expression were apparent in animals operated at all three developmental stages. These findings indicate that both immature and adult corticospinal neurons respond to axonal injury in a manner that is distinctly different from the peripheral neuron response. PMID- 8457897 TI - Recovery potential of muscle after partial denervation: a comparison between rats and humans. AB - The response to partial denervation is compared for the tibialis anterior muscle in the rat and the thenar muscle group in the human. Partial denervation in the human was a result of spinal cord injury, while partial denervation in the rat was induced by sectioning of the L4 ventral root. In some animals, a spinal cord transection at the T12-13 level was also performed to determine whether spinal cord injury affected the sprouting capability of motoneurons caudal to the injury site. Motor units were isolated by intramuscular microstimulation in the human and by ventral root splitting in a terminal experiment in the rat. Motor unit numbers were estimated by dividing the amplitude of the electromyogram (EMG) and the peak twitch force in response to maximum stimulation of the muscle nerve by the average unit EMG and twitch force, respectively. In both the rat and the human, surviving motor units enlarged as a function of the degree of partial denervation. Moreover, all surviving motor units appeared to enlarge proportionately. The limit to sprouting was tested systematically in the rat. On average, single motor units enlarged up to about five times their original size, resulting in the ability to compensate for up to 80% of motoneuron loss. The reason for this limit remains unclear, but histological data suggest that sprouting may be confined to the more distal regions of the motor axon, such that reinnervation of denervated muscle fibers is confined to the territory of the original motor unit. PMID- 8457898 TI - Developmental regulation of regenerative specificity in the bullfrog. AB - The accuracy with which motor axons reinnervate the hindlimb following ventral rhizotomy was studied in the bullfrog (Rana catesbeiana) by mapping the locations within the lumbar lateral motor column of motoneurons retrogradely labeled with horseradish peroxidase. At early stages of development, axons regenerate to the correct hindlimb region. In older tadpoles and frogs, axons appear to regenerate to targets determined by basal lamina tubes, which persist in the distal nerve stump after the severed nerve fiber degenerates. Basal lamina tubes develop at the stages when regenerative specificity is no longer expressed. These results led to the hypothesis that guidance cues may be present in older animals, and axons may be capable of responding to these cues, but are prevented from doing so because they are confined in basal lamina tubes. Results obtained from crosstage hindlimb transplants are consistent with this hypothesis. PMID- 8457899 TI - Gonadal steroids as promoting factors in axonal regeneration. AB - In this article, some of the trophic actions of gonadal steroids on receptor concentrating neurons within the mammalian brain and spinal cord will be discussed. This will be followed by a summary of our recent data identifying a new role for gonadal steroids as therapeutic agents in neuronal injury and repair. PMID- 8457900 TI - The response of central glia to peripheral nerve injury. AB - Microglial and astroglial cells undergo prompt responses to peripheral motor and sensory axon injury. These responses include proliferation of microglial cells as well as hypertrophy and increased levels of glial fibrillary acidic protein around the axotomized motoneurons and in the central projection territories of peripherally axotomized sensory ganglion cells. Proliferating microglial cells migrate towards reacting motoneurons, however, without directly apposing their cell membrane. Astroglial cells, on the other hand, increase their structural interrelationship with reacting motoneurons, seemingly at the expense of some presynaptic terminals. In sensory projection areas, microglial cells phagocytose degenerating axons and terminals. Beyond these observations, the functional role of the central glial cell response to peripheral nerve injury is obscure. PMID- 8457901 TI - Syngeneic grafting of adult rat DRG-derived Schwann cells to the injured spinal cord. AB - A subdural inflatable micro-balloon was used to induce closed traumatic contusion to adult rat spinal cord. This spinal cord injury model was associated with reproducible and graded neurological deficits and histopathological alterations. At various delays after injury, transplantations of syngeneic adult cultured dorsal root ganglion-derived Schwann cells were performed into the spinal cord lesion. The transplants were well integrated and reduced the microcystic posttraumatic cavitation as well as the gliosis. Schwann cells transplants were invaded by numerous regenerating neurites most of which, based upon their neurotransmitter contents, seem to originate from the dorsal root ganglion. PMID- 8457902 TI - Lesion-induced re-expression of neonatal recognition molecules in adult rat cerebellum. AB - It has been previously shown that sectioning of parallel fibers in the cerebellar molecular layer of adult rats gave rise to rapid reinnervation of the target cells, i.e., Purkinje cells. This paper reports that such a reinnervation is accompanied by reexpression (partial and total) of two developmentally regulated complementary molecules. These are an endogenous mannose-binding lectin, called R1, which reappears at the surface of the dendrites of Purkinje cells, and an endogenous glycoprotein ligand of R1, the 31 kDa glycoprotein, which seems to be neosynthetized and transported to the surface of parallel fibers. In this system, embryonic N-CAM is not reexpressed in neurons but reappears in reactive astrocytes in the vicinity of the lesion. The reexpression of recognition molecules (lectin and glycoprotein ligand) involved in normal synaptogenesis, may constitute the molecular basis for repair of nervous circuits in the adult as well. PMID- 8457903 TI - Cerebellar stimulation modulates thalamic noxious-evoked responses. AB - Parafascicular (PF) neurons responding to noxious stimuli and focal electrical stimulation of midbrain, diencephalon, and hypothalamic nuclei, which send projections to PF, modulates the PF spontaneous and noxious-evoked responses. Some cerebellar efferents ascend to PF. This investigation attempted to study the effect of cerebellar stimulation on spontaneous and noxious-evoked PF neuronal activity in rats. It was observed that 26% (73/280) of PF neurons responded to a noxious stimulus. The PF neuronal population exhibits two cell types according to their response pattern following the noxious stimulus. One type of PF neurons were excited (n = 53) and were classified as nociceptive-on cells. The second type of PF neurons responded to noxious stimulus by a decrease in the ongoing firing rate (n = 20) and were classified as nociceptive-off cells. The responses of these two types of nociceptively identified cells were tested following cerebellar lateral nucleus stimulation (Lat.N.S.) utilizing several current intensities. Lat.N.S. with lower intensities (0.1-0.2 mA) elicited suppression of both spontaneous and nociceptive-evoked discharges of the nociceptive-on neurons, although higher intensities (0.4-0.6 mA) elicited excitation on both discharges of this type of neuron. In contrast, Lat.N.S. induced a monophasic intensity dependent suppression of both the spontaneous and the nociceptive-evoked discharges of the nociceptive-off neurons. The results indicate that Lat.N.S. modulates the nociceptive-evoked responses of PF neurons. The possible role and related pathways of cerebellum in modulating noxious input were discussed. PMID- 8457904 TI - Buspirone-induced carbohydrate feeding is not influenced by route of administration and nutritional status. AB - Rats were habituated to ad lib food intake from two isoenergetic diets that differed in carbohydrate and protein content. To examine the route of administration effect, buspirone (0.6, 1.0, and 1.4 mg/kg) was injected into satiated rats either subcutaneously or intraperitoneally. Overall, no route of administration effect was observed; however, when results of the lowest dose were analyzed separately, the subcutaneous route was more effective than the intraperitoneal route. Regardless of route of administration, buspirone increased food intake over the first 2 h of food presentation in a dose-dependent manner. Moreover, the increase was entirely attributed to increases in intake from the high carbohydrate diet. In the subsequent experiment, the effect of buspirone (0.6 mg/kg) was examined in both satiated (early light period) and nonsatiated rats (early dark period). Both groups responded to buspirone with an increase in carbohydrate intake. Despite differences in baseline intake, the absolute increase was similar between satiated and nonsatiated rats. These data suggest that both sensitivity and selectively of buspirone-induced feeding are neither influenced by route of administration nor nutritional status of rats. PMID- 8457905 TI - Differential expression of serotonin and [Met]enkephalin-Arg6-Gly7-Leu8 in neurons of the rat brain stem. AB - The hypothesis that serotonin (5-HT) and [Met]enkephalin-Arg6-Gly7-Leu8 (MEAGL) coexist in the rat brain stem raphe nuclei was tested by a technique combining histofluorescence with immunocytochemistry, after treatment with colchicine and nialamide. In midbrain and pons serotonergic cell groups (B5-B9), no coexistence of 5-HT and MEAGL was detected. In serotonergic cell groups of the medulla oblongata (B1-B3), only 0.3-1.5% of 5-HT-fluorescent cells were MEAGL immunoreactive. These findings suggest that putative 5-HT and MEAGL are mostly expressed in different populations of neurons in the rat raphe nuclei. PMID- 8457906 TI - Effect of diet-induced obesity and experimental hyperinsulinemia on insulin uptake into CSF of the rat. AB - We examined the hypothesis that the uptake of plasma insulin into cerebrospinal fluid (CSF) is saturable in two rat models. Dietary obese and control female Osborne Mendel rats received 24-h infusions of vehicle or insulin. CSF insulin levels in cafeteria- and chow-fed rats were comparable at all levels of plasma insulin (4.5 +/- 2.8, 7.6 +/- 2.4, and 23.9 +/- 6.4 microU/ml in cafeteria diet vs. 4.5 +/- 0.9, 6.8 +/- 1.1, and 17.0 +/- 4.0 microU/ml in chow rats). CSF insulin uptake as a percentage of plasma insulin decreased with increased plasma insulin in both groups. A similar relationship was observed in Wistar rats receiving 6-day infusions of vehicle or insulin (plasma insulin = 55 +/- 12 vs. 365 +/- 98 microU/ml; CSF/plasma insulin ratio = 0.022 +/- .007 vs. 0.013 +/- .006, respectively). Hyperinsulinemic Wistar rats did not demonstrate decreased brain capillary insulin binding vs. vehicle-infused controls. The results suggest that a saturable transport process contributes insulin transport into CSF in normal rats and that this process is not altered by moderate diet-induced obesity or hyperinsulinemia per se. PMID- 8457907 TI - Lesions of the lateral parabrachial nuclei disrupt aversion learning induced by electrical stimulation of the area postrema. AB - The research about the neural basis of taste aversion learning (TAL) has pointed out the area postrema (AP) as a fundamental structure implied in the processing of certain toxic stimuli. Likewise, recent studies demonstrated that electric stimulation of the AP is an efficient substitute of the aversive stimulus. The lateral parabrachial nucleus (PBN1), one of the subnuclei of the parabrachial complex, is the main anatomic rostral connection of the AP. In the experiment presented here, we demonstrate that TAL induced by electric stimulation of the AP is interrupted when the PBN1 is lesioned, thus giving support to the functional role of this anatomic system (AP-PBN1) in the codification of aversive stimuli processed by the AP. PMID- 8457908 TI - Calcium channel blockade attenuates angiotensin II-induced drinking in rats. AB - Lateral ventricular administration of angiotensin II (ANG II) produces potent dipsogenic effects in water-sated rats. ANG II seems to require functional voltage-gated calcium channels on neurons throughout circumventricular brain sites to exert its effects. Although there are at least three types of calcium channels, only L-type calcium channel-blocking drugs have been reported to decrease drinking. (4-(4-Benzofurazanyl)-1-4-dihydro-2,6-dimethyl-3,5-pyridine dic arb oxylic acid methyl 1-methyl-ethyl ester) [PN 200-110; isradipine (ISR)], a selective L-type calcium channel blocker, has been shown to attenuate significantly the intake of sweetened water in water-sated rats following either peripheral or ICV administration, but ISR does not affect plain-water intake in water-deprived rats. The present experiment was designed to determine whether ISR would attenuate ANG II-induced drinking that is not either motivated by palatability or dependent on deprivation. Rats, each fitted with chronic indwelling ventricular cannulae, were pretreated with ISR (0.3, 3.0, and 30 micrograms/rat; ICV). ANG II (40 ng/rat; ICV) was administered 10 min later and rats were allowed free access to water for 15 min. Injections of ANG II plus saline and ANG II plus the ISR vehicle (dimethyl sulfoxide) did not attenuate ANG II-induced polydipsia, whereas ANG II+ISR (0.3 and 3.0 micrograms) attenuated ANG II-induced drinking to 62 and 22% of control, respectively. Results with the 30 micrograms dose were not different from the 3.0 dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457910 TI - Effects of neonatal adrenalectomy on 5-HT and TRH-like immunoreactivity in the rat spinal cord. AB - This study investigated the effects of neonatal unilateral adrenalectomy on the serotonin- (5-HT) and thyrotropin-releasing hormone-like immunoreactivities (TRH LI) in the intermediolateral cell column (IML) of the rat spinal cord where the sympathetic preganglionic neurons innervating the adrenal medulla are located. The density of the innervation was measured by a computer-assisted image analysis. Two weeks after the lesion, only one rat (1/3) showed a 30% decrease of 5-HT-LI in the ipsilateral IML, although no modifications were observed for TRH LI. At 1 month, we observed a variable decrease of 19% to 30% for either 5-HT- or TRH-LI in the ipsilateral IML. However, one animal (1/3) showed nonsignificant modifications. At 3 months, we showed a 17% mean loss of 5-HT-LI and TRH-LI in the ipsilateral IML. However, the decreases of 5-HT-LI and TRH-LI did not always appear similar. These results appear different from those obtained after neonatal removal of the superior cervical ganglion. PMID- 8457909 TI - 5' Deiodinase activity in brain regions of adult rats: modifications in different situations of experimental hypothyroidism. AB - In the central nervous system, type II 5' deiodinase (5'D-II) is highly regulated, as judged by the dramatic changes in enzyme levels observed after abrupt alterations in thyroid status. In this work, the 5'-DII activity has been studied in different situations of experimental hypothyroidism (propylthiouracil, methimazole, thyroidectomy, and low iodine diet), in various brain regions (pituitary, cerebellum, brain stem, hypothalamus, cortex, and whole brain) in adult rats. Propylthiouracil and methimazole significantly increase the activity in all brain regions. These increases are higher in rats treated with methimazole. Thyroidectomy significantly increases the activity in cortex and pituitary. A low iodine diet significantly increases in all brain regions except in the hypothalamus. The concentration of triiodothyronine (T3) studied in the major brain regions remained unchanged. The results obtained show a compensatory mechanism in pituitary and other brain regions in order to maintain the T3 levels in brain tissue. PMID- 8457911 TI - Production of an affinity-purified antibody against an aldehyde-treated neurofilament protein for use in immunocytochemistry. AB - Fixation enhances cellular morphology and reduces loss of molecules during tissue processing. Antibodies against fixation-resistant epitopes are very useful, because they allow an immunocytochemical detection in tissue of better preserved morphology. However, fixatives can alter antigenicity and adversely affect the result of immunohistochemical procedures. To address this problem, this study examined the feasibility of generating antibodies to a paraformaldehyde-fixed antigen for use in immunohistochemical procedures. The large subunit of neurofilament proteins was selected for this study. Crude neurofilament proteins were isolated and separated by SDS-polyacrylamide gel electrophoresis. The large subunit of neurofilaments (NF-H) was electroeluted from the electrophoresis gel and exposed to paraformaldehyde, and used for immunization of a rabbit. The rabbit antiserum was affinity purified on CNBr-sepharose immobilized neurofilament proteins. On Western blots, the antibody reacted with the NF-H protein in a phosphorylation-dependent manner. In aldehyde-fixed cerebellum, the antibody strongly stained axons. In contrast, in alcohol-fixed cryostat sections the immunocytochemical detection was substantially reduced. The procedure presented in this study, involving a simple pretreatment of the immunogen, allows for the generation of an antibody that may be used in immunohistochemical studies where localization of the immunogen may be reduced or even lost by aldehyde fixation. PMID- 8457912 TI - Early postnatal estrogen organizes sex differences in the extinction of a CRF running response. AB - In the present study the organizational effects of sex steroids on the sexually dimorphic extinction of a continuously food-rewarded running response were investigated. Gonadally intact female rats neonatally treated from day 1 to day 8 of the postnatal life with estradiol benzoate (EB), dihydrotestosterone (DHT) or vehicle, and males treated in the same period with the antiandrogen ciproterone acetate (AC), the estrogen antagonist tamoxifen (TX) or vehicle were studied in adulthood during the acquisition and extinction phases of the response in a short and narrow runway. No difference in performance between groups was obtained in the response acquisition. However, during extinction control males extinguished faster than control females. DHT treatment to females and neonatal CA administration to males had no effect on the expression of sexual dimorphism. Conversely, TX administration to the males increased male's resistance to extinction at the levels shown by control or DHT females, whereas the females treated with EB exhibited similar extinction rates to those observed in nonhormonal treated or CA males. This finding suggests that the organizational effect of testosterone on the sexually dimorphic behavior studied in the present report are mediated by testosterone conversion to estradiol throughout the aromatization pathway in the brain. PMID- 8457913 TI - Effects of damage to SCN neurons and efferent pathways on circadian activity rhythms of hamsters. AB - This experiment was designed to determine if entrainment to a light:dark (LD) schedule and the free-running rhythm in constant light are altered by partial lesions of suprachiasmatic nuclei (SCN) cells or SCN output pathways. Twenty-four male golden hamsters were housed under 12L:12D. Hamsters received either lesions (n = 16), sham surgery (n = 4), or no surgery (n = 4), and were placed into individual cages with running wheels under 14L:10D. Each time after 4 weeks, the LD schedule was phase advanced by 6 h, phase delayed by 6 h, and then the animals were exposed to constant dim light. At the end of the experiment, brain sections were processed for peptide histidine isoleucine (PHI) and gastrin releasing peptide (GRP) immunohistochemistry. Alternate sections were stained for cells and fibers. Behavioral results indicate that (a) very few SCN cells and SCN efferent fibers, as labeled by PHI and GRP immunohistochemistry, are necessary for the expression of circadian rhythmicity in wheel running, and (b) damage to pathways rostral to the SCN may be more critical for entrainment and rhythmicity than damage to caudal pathways. Targets of PHI- and GRP-immunoreactive SCN efferent fibers were also identified. PMID- 8457914 TI - Intrastriatal injection of choline accelerates the acquisition of positively rewarded behaviors. AB - The prediction was made that by increasing the synthesis of striatal acetylcholine, through local injection of its precursor choline, the acquisition of a lever-pressing response in two different autoshaping situations would be accelerated. In the first experiment, choline was injected into the striatum or parietal cortex of rats immediately after dipper training; 24 h later and during 5 consecutive days the animals were submitted to an autoshaping procedure of the operant kind. In the second experiment, choline was administered to the same regions shortly after each of three classical-operant autoshaping sessions; during the next two sessions, autoshaping contingencies of the operant kind were in effect. In both experiments choline injection into the striatum induced a marked facilitation of acquisition of the conditioned responses, although cortical injection of choline produced a milder improvement only in the first experiment. These results indicate that striatal cholinergic activity is, indeed, involved in the early phases of positively reinforced learning. PMID- 8457915 TI - 5-HT-dependent myoclonus in guinea pigs: mediation through 5-HT1A-5-HT2 receptor interaction. AB - Investigations utilizing agonists for 5-HT receptor subtypes have been conducted to determine which 5-HT receptor subtype(s) subserve myoclonus in the guinea pig. Administration of a nonselective 5-HT agonist such as 5-MeODMT (5-HT1A/5-HT2 agonist) induces a dose-dependent behavior characterized by head jerking at low doses (1-2 mg/kg, SC) and full-blown myoclonus (continuous rhythmic whole-body jerking) at higher doses (2.5-5 mg/kg, SC). In contrast, the selective 5-HT1A receptor agonist 8-OH-DPAT and the selective 5-HT2 receptor agonist DOI do not induce myoclonus, and elicit only limited head jerking across an otherwise behaviorally active range of doses (1-5 mg/kg, SC). Importantly, the coadministration of both 8-OH-DPAT and DOI results in the emergence of dose dependent myoclonic behavior. These data suggest that coactivation of 5-HT1A and 5-HT2 receptors may be required for the induction of myoclonus in the guinea pig. PMID- 8457916 TI - Extinction of cocaine-induced place approach in rats: a validation of the "biased" conditioning procedure. AB - It has often been demonstrated that when a rat is conditioned in a cue-specific environment that has been repeatedly paired with cocaine injections, it will spend more time in that environment than it does in a saline-paired environment. This behavioral procedure is commonly known as the conditioned place preference (CPP)-test. At present, a firm theoretical understanding of the mechanisms underlying the production of a CPP are unknown. It is insufficient merely to know that a CPP can result after repeated drug pairings. Rather, it is necessary that the procedure is validated within a learning theory framework. The objective of the present study was, therefore, to establish that what is observed in place preference studies was, indeed, conditioning. This was accomplished by determining whether a cocaine-induced increase in time spent in a drug-paired environment was subject to attenuation following extinction trials. Rats were tested for their initial bias in spending more time in one of two stimulus specific chambers of a place-conditioning apparatus. On four occasions, rats were injected with 2.5 mg/kg cocaine and confined to their less-preferred chamber whereas, on four alternating sessions, they were conditioned with saline (vehicle) in their preferred chamber. Subsequent testing in the nondrugged state revealed that these rats displayed a significant increase in the time spent in their initially least-preferred environment compared to baseline measurements. Following establishment of this cocaine-induced CPP, the rats were injected only with saline and conditioned for an equal number of sessions (i.e., four).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457917 TI - Female sexual behaviors in male rats with dorsal raphe nucleus lesions: treatment with p-chlorophenylalanine. AB - The effects of the serotonin-synthesis inhibitor, p-chlorophenylalanine (PCPA) on female sexual behaviors were examined in male rats with or without lesions (DRL) of the dorsal raphe nucleus, which contains a large number of serotonergic cell bodies. Estrogen-primed castrated males without brain surgery (control) showed extremely low levels of lordosis compared with females. On the other hand, DRL males displayed lordosis response more frequently than control males, but the lordosis quotient (LQ) in this group was lower than that in females. As well as DRL males, all PCPA-treated males showed lordosis, the mean LQ being comparable to the DRL group. Thus, the destruction of the dorsal raphe nucleus or the deprivation of serotonin by PCPA treatment facilitates manifestation of lordosis behavior in male rats. However, synergistic effect of DRL and PCPA treatments on female sexual behaviors have not been observed. The mean LQ in PCPA-treated male rats with DRL was almost the same as in DRL males or PCPA-treated males. These results suggest that the possible site of action of PCPA in regulating female sexual behavior in male rats is the serotonergic neurons in the dorsal raphe nucleus. Furthermore, the lordosis-facilitating effect of DRL is due to destruction of the serotonergic cell bodies in the dorsal raphe nucleus. PMID- 8457918 TI - Auditory-responsive units in the midbrain vocal nuclei in the ring dove (Streptopelia risoria). AB - The avian midbrain vocal control nucleus, n. intercollicularis (ICo), receives inputs from midbrain auditory nucleus and from a subdivision of auditory thalamus, suggesting a possibility of auditory response units in the ICo. Using single-unit recordings, we explored auditory response units throughout the dorsomedial midbrain of female ring doves under deep general anesthesia (acute preparation). We found exclusively in the ICo, units that responded preferentially to taped courtship coos of conspecifics (male or female coos) and units that responded to specific frequencies present in coos. Units in the midbrain auditory nucleus also responded to these auditory stimulation in a tonotopic fashion, and were responsive to tone burst as well. The results, along with data from other experiments, suggest that species-specific sound responsive units within the ICo may mediate acoustically facilitated female coos and endocrine responses of the ring dove. PMID- 8457919 TI - Heritability and diagnosis of congenital abnormalities in food animals. AB - The heritability and diagnosis of congenital abnormalities in food animals have been reviewed from the viewpoint of practitioners, clinicians, and researchers. At least 632 putative mutant genes have been cataloged and listed according to the principal body system affected and mode of inheritance (see Tables 1 and 2). Implications of recent advances in genetic methodology are noted. PMID- 8457920 TI - Congenital skin abnormalities. AB - It must be remembered that viral infections and maternal nutritional deficiencies can and do cause congenital skin diseases and must be included in a complete differential diagnosis list. These disorders are covered adequately in most current texts on infectious and nutritional diseases and therefore are not described here. When an hereditary, congenital skin disease is suspected, biopsy specimens should be submitted for diagnosis. Many breed associations have control programs for these types of diseases and only with veterinary and producer cooperation will these programs be successful. PMID- 8457921 TI - Chromosome abnormalities. AB - Chromosome abnormalities have been described in food animals since 1964. Some are self-limiting because they cause sterility or other developmental defects incompatible with normal growth and development, making them unacceptable for production systems. Others, however, cause no discernible phenotypic abnormalities but, in breeding animals, result in increased levels of embryonic mortality and reduced litter size. Although the extent of loss of reproductive efficiency is not entirely understood at this time, care must be exercised in recommending animals carrying a chromosome abnormality to be used as breeding stock. This is of particular concern if animals are to be used extensively in artificial insemination programs. PMID- 8457922 TI - Congenital abnormalities of internal organs and body cavities. AB - Many of these malformations are reported sporadically, but a few are common, and several have important clinical implications. One example is schistosomus reflexus, which is always a challenge for veteran clinicians and often baffling to inexperienced obstetricians. The recent finding that early palpation of the amniotic vesicle can cause intestinal atresia in calves is extremely significant for dairy practitioners. Finally, there is the ethical question in breeding animals--repairing defects that are thought to be genetic, such as atresia ani, scrotal hernia, and umbilical hernia. PMID- 8457923 TI - Congenital abnormalities of the genitalia of cattle, sheep, goats, and pigs. AB - The essential steps in embryology of the genitalia and its sexual differentiation, are briefly reviewed. The major intersex states in domestic ruminants and pigs are briefly considered. Major attention is directed to anomalies of the reproductive organs of mature female and male animals that are likely to compromise fertility. Emphasis is placed on clinical and pathologic findings and on occurrence and pathogenesis of recorded defects. PMID- 8457924 TI - Congenital duplication. AB - Almost all types of congenital duplication described in humans have been observed in food animals, and a number are illustrated in this article. Congenital duplications, especially conjoined symmetric twins, are relatively common defects in cattle. The incidence is less in sheep and in hogs, and they appear to be rare in goats. In cattle, cranial duplication is predominant; this is in contrast to caudal duplication in sheep and hogs. These differences among species are interesting and may explain why congenital duplications appear more frequently in cattle than in other domestic animals. Based on the number of eyes and ears, classification criteria for cranial duplications are proposed. The cause of congenital duplications is not known. PMID- 8457925 TI - Congenital diseases and abnormalities of pigs. AB - Several congenital developmental anomalies are not listed in this review because they have no proposed cause. It is the author's hope that this article will serve practicing veterinarians and the swine industry by being an informative guide for stimulating independent thought toward diagnosing congenital diseases. Remember that the cause may have exerted its effects weeks or months before being observed. A detailed history of the dam as well as the rest of the herd is important. If possible, a history of neighboring herds should also be examined for similar problems. Either conduct a thorough necropsy with appropriate tissues submitted for diagnostic analysis, or send representative pigs to a diagnostic center for a complete evaluation. If chromosome evaluation is desired, contact the evaluating laboratory for submission procedures. Breeding records should be evaluated for intragenerational frequencies and intergenerational patterns typical of genetic transmission. When evaluating pedigrees, the frequent occurrence of an individual is not proof of its involvement. The frequency of occurrence in the diseased population must be significantly greater than it is in a random population of pigs. Dr. H.W. Leipold, in the pathology department at the Kansas State University College of Veterinary Medicine, maintains an extensive database of congenital anomalies in domestic animals. I recommend that he be contacted in all cases of undiagnosed or unusual cases of congenital disease. He possibly can help with a definitive diagnosis and your contact will help expand this important central database of congenital diseases. PMID- 8457926 TI - Congenital abnormalities of the goat. AB - Congenital abnormalities of genetic and environmental causes constitute a striking proportion of the afflictions seen in goats. These include a variety of malformations and metabolic diseases that could occur in all breeds but tend to exhibit predisposition in some breeds of goats. Genetic abnormalities for which the carrier state is detectable with the aid of enzymes and surface protein markers can be eliminated from goat populations, whereas common polygenic disorders including udder problems in does and gynecomastia in bucks are more difficult to eradicate because the mutant genes responsible for these traits generally do not declare themselves until inbreeding brings together a critical concentration of liability genes to create a crisis. A substantial reduction of common abnormalities in this species, such as intersexuality in dairy breeds, abortion in Angora breed, and arthritis in the Pygmy breed, will require a change in breeders' preference and selection practice. In making these changes, however, the beneficial traits will have to be balanced against the undesirable effects of the selected mutant genes (pleiotropy), which hold the key to success or failure of a breed under domestication. PMID- 8457927 TI - Congenital defects of sheep. AB - With increasing incrimination of viruses, plants, and drugs as causes of ovine congenital defects, concerted efforts are required to identify environmental teratogens. Expanding knowledge of congenital defects requires studying as many defective lambs as possible; recording and documenting; detailed diagnostic examinations; genetic analyses and chromosomal examinations, whenever possible; and field investigations. Adopting standardized classification, terminology, and diagnostic procedures should improve descriptions, diagnoses, and interdisciplinary exchange of information. That, in turn, should improve our knowledge of and diagnosis of congenital defects of sheep in the future. Finally, veterinary clinicians and diagnosticians are encouraged to take an interest in congenital defects and teratology. PMID- 8457928 TI - Quinolizidine and piperidine alkaloid teratogens from poisonous plants and their mechanism of action in animals. AB - Quinolizidine and piperidine alkaloid teratogens from Lupinus, Conium, and Nicotiana genera have been identified as causes of birth defects in livestock induced by poisonous plants. Many defects now known to be related to poisonous plant ingestion were once thought to have a genetic origin. This supposition delayed diagnosis, reporting, and understanding of such birth defects, because breeders and producers feared the news would make it difficult to sell breeding stock. Defects caused by quinolizidine and piperidine teratogens include cleft palate and contracture-type skeletal defects such as arthrogryposis, scoliosis, torticollis, and kyphosis. Teratogens have been identified, differences in susceptibility to teratogenic compounds among livestock species have been elucidated, periods of gestation when specific types of birth defects occur have been determined, and information about mechanism of action has been developed. PMID- 8457929 TI - Lysosomal storage diseases in livestock. AB - Lysosomal storage diseases may be inherited or acquired. The former are usually inherited as autosomal traits, and heterozygotes may be identified by having enzyme activity levels approximately midway between normal and diseased values. Founder effect, enhanced by widespread acceptance of artificial breeding technologies, has been important in the spread of these genetic diseases in cattle. Acquired storage diseases of importance to livestock most frequently are plant intoxications. PMID- 8457930 TI - Inherited enzyme deficiencies in livestock. AB - The biochemical basis of over 300 inherited diseases has been defined in humans, and the majority involve abnormalities in enzymes. The rate of discovery of new defects is accelerating as biochemical and molecular technologies improve. The majority of inherited defects are expressed before puberty and approximately 25% are apparent at birth. Genomes of other mammals are similar and have been subjected to similar mutation pressures; therefore, it is probable that a range of inherited defects exists in livestock similar to that in humans. Because modern livestock populations have emerged from small population bases, the range of genetic aberrations, within breeds, will be less than in the general human population. Even if there is a 10-fold difference, however, there will be a bewildering array of defects possible in each breed. Because the level of inbreeding within livestock populations is greater than in the general human population, on the other hand, the prevalence of specific defects will be higher. It is probable that a high prevalence of a lethal recessive defect could occur within a particular livestock population and escape recognition. First, livestock producers accept a relatively high neonatal mortality rate without seeking a diagnosis. Second, few if any veterinary diagnostic facilities possess either the instrumentation or the analytic skills essential for investigating the vast range of potential inborn errors of metabolism. Third, national selection programs- e.g., those employed within the dairy industry--tend to use production data from adult progeny in selection. Consequently, the programs would not detect differences in fetal or neonatal mortality rates among descendants of specific sires until a deleterious defect had been widely disseminated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457931 TI - Primary immunodeficiencies of food animals. AB - Although there are few, well-characterized PIDs of food animals, these diseases are important because they tend to be severe and with no cure. Most animals with PID do not receive the intensive and aggressive care required for survival: Veterinarians may be consulted only when the animals are in the terminal stages of illness; it is generally not economically practical for livestock producers or practitioners to pay for the exhaustive laboratory tests required to detect and characterize these anomalies. Another reason for the small numbers of characterized clinical cases of PID is that they are rare. It is possible, however, that intensive artificial insemination and embryo transfer could select for heterozygous carriers of these autosomal traits. As seen with bovine leukocyte adhesion deficiency, as the frequency of an allele increases in the population, the numbers of affected animals increase. Furthermore, other immunodeficient syndromes are likely to exist. Veterinarians therefore should be aware of these disorders and should seek laboratory assistance to arrive at a correct diagnosis. Because of the inheritable nature of PID, livestock producers need assistance from veterinarians to identify carriers and establish sound breeding and control programs. One positive outcome from studies of PID is that research scientists and veterinarians learn much about immune systems from these afflicted animals. In fact, these animals may become models for gene therapy or marrow reconstruction procedures. PMID- 8457932 TI - Congenital defects of the bovine central nervous system. AB - What should you do if you observe a defective calf in a herd? Our suggestion is to seek qualified help to examine and diagnose the condition. Parentage should be verified by blood typing. But, most important, you can keep cattle genetically clean by having your clients report all defects in calves to their breed association and artificial insemination centers. PMID- 8457933 TI - Congenital defects of the bovine musculoskeletal system and joints. AB - A variety of structural and functional congenital defects affecting the central nervous system of cattle have been identified. This article discusses specific defects of the central nervous system. Spastic and paralytic, metabolic, and storage diseases are reviewed. PMID- 8457934 TI - Beginning the search for a patient-care computer system for nursing. PMID- 8457935 TI - Mapping the future of hospital information systems: priorities for nursing applications. AB - The purpose of this study was to determine the value of computerized applications to nurse users in a large acute-care university-affiliated hospital. A hospital information system has been in place since 1983. A convenience sample of 77 staff nurses and 33 nurse managers from various clinical areas rated the benefits for decision making and patient care of approximately 19 existing automated applications, and prioritized for future acquisition, approximately 40 applications not currently available. Results of the study revealed that of the applications currently automated, respondents ranked the applications of results reporting, order entry, nursing station census, and message switching as most useful for decision making and patient care. Applications identified as high priorities for future acquisition were on-line charting, automated medication record, and enhanced results reporting. PMID- 8457936 TI - The nurse engineer: a way to better nursing information systems. AB - Currently, there are few significant nursing information systems that can meet the basic needs of nursing (Zielstorff, McHugh, & Clinton, 1988). Some factors that may relate to this problem include the amount of nurse input, the effectiveness of communications between nurses and engineers, and the state of nursing practice. One method that may address this problem is to involve nurse engineers, nurses with technical degrees, in the development process. As a key member of the development team, the nurse engineer can encourage intensive use of nurse input, function as a translator and clarifier, thereby reducing communication problems, and assist the development team to analyze the diversity in nursing practice. Using nurse engineers in the development process may result in better nursing information systems. PMID- 8457937 TI - Effectiveness of computer assisted instruction and small-group review in teaching clinical calculation. AB - This study compared the effectiveness of computer assisted instruction (CAI) and small-group review in teaching clinical calculation to associate degree nursing (ADN) students. Subjects were 123 ADN students randomly assigned to receive 50 minutes of supplemental instruction in clinical calculation by means of CAI or small-group review. Both CAI and small-group review were based on Gagne's events of instruction. An analysis of covariance of the scores on a 20-item exam, developed by five expert faculty members and having a Kuder-Richardson Formula 20 (KR-20) of 0.74, revealed no significant difference in performance between groups. The authors concluded that, when teaching strategies are comparable, CAI is as effective as small group review among ADN students for supplemental instruction in clinical calculation. PMID- 8457938 TI - Student nurses' conceptions of computer use in hospitals. AB - In this article, the author reports on a study that investigated the conceptions and attitudes of community college diploma nursing students toward the use of computers in hospitals. Data were collected during 35 audio-taped interviews, which were analyzed using the constant comparative method. Findings indicated that students had little understanding of how computers are used by nurses today and how they might be used in the future. Four categories of student conceptions of the use of computers by hospital-employed nurses emerged: workload, patient care, image, and professionalism. Conceptions within each category were grouped into subcategories that supported the notion that hospital employed nurse's work was enhanced or detracted from by computer use. Although the majority of students had a positive attitude toward computer use by nurses, their conceptions differed in quality or complexity in direct proportion to the year in the program and their amount of clinical experience. Nurse educators have a two-fold responsibility: 1) to foster positive attitudes toward computer use; and 2) to facilitate the learning process so that students' levels of conception increase throughout the nursing program. PMID- 8457939 TI - Bedside/point-of-care technology: the 'window' into the integrated clinical database. PMID- 8457940 TI - Prevention of occupational disease. PMID- 8457941 TI - Isoniazid toxicity with cerebellar ataxia in a child. PMID- 8457943 TI - Where should our new doctors come from? PMID- 8457942 TI - Legalization of all drugs. PMID- 8457944 TI - Where should our new doctors come from? PMID- 8457945 TI - Where should our new doctors come from? PMID- 8457946 TI - Where should our new doctors come from? PMID- 8457947 TI - Where should our new doctors come from? PMID- 8457949 TI - Recent changes in licensure regulations. PMID- 8457948 TI - Saving Medicare in Canada. PMID- 8457950 TI - Sexual harassment at medical schools. PMID- 8457951 TI - Drug nomenclature: special notice from the CMA. PMID- 8457952 TI - Paying physicians in teaching hospitals. PMID- 8457953 TI - Ethics and clinical practice guidelines. PMID- 8457954 TI - Alternative funding plans: is there a place in academic medicine? AB - Because of shrinking resources and the resulting threat to its academic vitality the Department of Paediatrics, Hospital for Sick Children, University of Toronto, entered into an agreement on alternative funding with the Ontario Ministry of Health in 1990. The department developed a set of principles that guided the negotiations, which ultimately led to a budget that formed the basis of the agreement. The contract with the ministry provides a global budget to the department; this budget funds faculty members, administrative staff and the educational and research programs formerly supported by fee-for-service billing to the Ontario Health Insurance Plan. The alternative funding plan has provided financial stability to the department and affords an opportunity to develop innovative and cost-effective models of pediatric care. PMID- 8457955 TI - The Emergency Drug Release Program: regulatory aspects of new drug access in Canada. PMID- 8457956 TI - Are worry-free transfusions just a whiff of ozone away? PMID- 8457957 TI - Comparison of cefoxitin and ceftizoxime in a hospital therapeutic interchange program. AB - OBJECTIVE: To determine whether (a) ceftizoxime can replace cefoxitin in the prevention and treatment of various infections in a major teaching hospital, (b) a previously applied two-stage intervention program is an effective method of instituting a therapeutic interchange of ceftizoxime for cefoxitin and (c) the replacement of cefoxitin with ceftizoxime results in a more cost-effective therapy. DESIGN: Two-phase, open, sequential study. SETTING: Tertiary care teaching hospital. PATIENTS: One hundred patients who received cefoxitin during the 6 months immediately before the start of the interchange program (phase 1) and 100 who received ceftizoxime during the 6 months immediately after the start of the program (phase 2) were randomly selected. RESULTS: The demographic characteristics of the two patient groups were similar except for sex (p < 0.05). The cefoxitin doses were usually given every 6 hours (in 33% of the cases) or every 8 hours (in 61%), whereas the ceftizoxime doses were usually given every 12 hours (in 98%). Prescriber distribution was stable throughout the study period, the Department of General Surgery being responsible for about 70% of the orders. Prophylactic indications accounted for over 60% of the treatment courses. The proportion of prophylactic treatment courses that resulted in a successful clinical outcome did not differ between the two groups (cefoxitin 92% and ceftizoxime 91%). Of the empiric or directed treatment courses clinical success or improvement was observed in 89% of the cefoxitin and 91% of the ceftizoxime recipients. Microbiologic eradication was seen in 65% of the cefoxitin and 90% of the ceftizoxime directed treatment courses. Pathogens isolated during therapy were similar in the two treatment groups. Diarrhea was the most common adverse effect, occurring in 8% of the cefoxitin and 10% of the ceftizoxime recipients; no Clostridium difficile or C.-difficile-producing toxin was identified in these patients. The ceftizoxime therapy was 36% less expensive than the cefoxitin therapy on average, and the annual savings was estimated to be $83,123. An estimated 5615 drug doses were avoided annually, for an additional savings of $24,875 in drug administration. Therefore, the total estimated annual cost savings resulting from this two-stage interchange program was $107,998. Given the cost of $4856 to implement and maintain the program, the estimated net savings for the first year was $103,142. CONCLUSION: Ceftizoxime can replace cefoxitin in the prevention and treatment of various infections. The form of evaluation described herein is valuable when any formulary modification is being considered in a hospital. PMID- 8457959 TI - Toxic effects from nitrogen dioxide in ice-skating arenas. PMID- 8457960 TI - On the patient. 1950. PMID- 8457958 TI - Clinical and epidemiologic characteristics of hepatitis C in a gastroenterology/hepatology practice in Ottawa. AB - OBJECTIVE: To examine the clinical and epidemiologic features of hepatitis C virus (HCV) infection in a gastroenterology/hepatology practice in Ottawa. DESIGN: Retrospective chart review. PATIENTS: Sixty-three consecutive patients found to be anti-HCV positive. Their charts were analysed with respect to risk factors, history of hepatitis, serum aspartate aminotransferase (AST) levels and the presence of hepatitis B markers. The long-term sexual partners of 29 patients agreed to undergo HCV antibody testing. RESULTS: Of the patients 48 (76%) had been exposed to HCV parenterally: 27 used intravenous drugs, and 21 had received blood or blood products. Eleven patients did not have any known risk factor (sporadic infection), but eight of them had lived in countries where hepatitis C may be more prevalent; the other three had locally acquired infection. The mean serum AST level at the first visit was 140 (normally less than 40) IU/L. At least one hepatitis B marker was identified in 33% of the patients. None of the sexual partners who were tested were anti-HCV positive. CONCLUSION: Most cases of hepatitis C in Ottawa are acquired through parenteral exposure; sexual transmission is rare. Sporadic infection in the Ottawa region is rare but may be more common in people from countries with a higher prevalence rate of hepatitis C. Most cases of hepatitis C are asymptomatic. PMID- 8457961 TI - It is ethically defensible to test potential immigrants for HIV, BC committee says. PMID- 8457962 TI - Illiteracy can have major impact on patients' understanding of health care information. PMID- 8457963 TI - National project to publicize link between literacy, health. PMID- 8457964 TI - Strategies outlined for balancing growth of MD, patient populations. PMID- 8457965 TI - Quebec, Ontario battle over cross-border health care charges. PMID- 8457966 TI - Aggressive recruiting of rural students may help end Newfoundland's shortage of rural MDs. PMID- 8457967 TI - The residency lottery. PMID- 8457968 TI - Quality, innovation and cost containment. AB - Quality, innovation, cost containment--these three criteria for change within the business world can be applied just as usefully within the realm of health care. Each of these criteria must be met by projects for change. By considering these aspects from the outset and by incorporating a means to measure all three, planners can ensure that change is beneficial. These three criteria also make it easier to monitor the change at regular intervals. Eventually, the project comes full circle, with the criteria used to establish the project's viability being used to report on its final results. PMID- 8457969 TI - Nurses' learning patterns. AB - Staff nurses are expected by nurse administrators and educators to incorporate nursing theory, diagnosis and researched-based interventions into highly technical patient care. However, there has been minimal systematic observation of how nurses learn in clinical practice and how that learning could be enhanced. Recently, an exploratory study was conducted to start filling that gap. PMID- 8457970 TI - Shaping health care policy. AB - At home and abroad, the Canadian health care system has long been regarded as one of the best in the world. However, it is facing internal and external pressures to change. There is a perception that the traditional system, with its emphasis on physician services and acute care hospital-based services, is being threatened. So, too, are the five principles--universality, accessibility, portability, comprehensiveness, and public administration--under which the system operates. PMID- 8457971 TI - Going home: easing the transition for the mentally ill. AB - Health care in the 90s dictates an increased pressure to discharge patients from the hospital into the community, placing much of the burden of care on families. With budget constraints in effect and bed shortages and closures a reality, the health care system is keenly aware of the need to prevent illness relapse and to promote safe functioning in the community, especially for people who suffer from persistent mental health problems. PMID- 8457972 TI - Laryngectomy: Grieving disfigurement and dysfunction. AB - When I (Weber) was three, my father had a total laryngectomy. His stoma did not bother me, and it was common to see him cough through his neck, though I never became used to the excessive secretions produced. My father mastered esophageal speech well, so communication was normal. No one in my family can remember what his voice was like before the operation. Knowing that people stared and whispered about my father, I warned new friends that my dad had a hole in his neck so he could breathe and that he might sound funny to them because he had no voice box. I did not want my friends to be frightened by a stoma that many people see as revolting. PMID- 8457973 TI - A place to call home. AB - When 54 year old Lisa was admitted to the Western Division of the Toronto Hospital in November 1987, it was for removal of a benign cranio-cerebral tumor. The pulmonary compromise she had lived with for many years--the result of a congenitally short spine--was accentuated during the months following surgery. With breathing difficulties and recurrent pneumonia, Lisa required assisted ventilation. And though she tolerated being off the ventilator for a total of five hours during the day, repeated attempts to wean her were unsuccessful. PMID- 8457974 TI - [Integration of a nursing model into a local community service center]. AB - Four years ago, maternal/child health nurses from the Metro CLSC in Montreal found themselves in a crisis situation. They were unable to evaluate their work- which consisted of varying tasks and the need for these nurses to be everywhere at the same time. A need to reflect on the situation prompted the team to meet for three hours twice monthly to analyze the problems and establish a plan of action. A nurse-counsellor guided the initial process. A post-natal home visit was chosen as an example for discussion. The group conceded that each member of the perinatal team had a different philosophy and nursing approach. The team consisted of nurses of various ages, experiences and educational backgrounds. Some nurses felt more comfortable expressing themselves in English while others preferred French. At times this group diversity hindered the communication of ideas as well as the ability to reach a consensus about required practice changes. The McGill Nursing model from McGill University was chosen and integrated into the team's practice. The author presents this model and outlines it's advantages and disadvantages. She illustrates this model with the use of an ecomap designed by Wright and Leahy (1984). This nursing model addresses the use of forces within each individual as well as the family. Since it takes into account the extended family, it allows a global approach to care. The article focuses on the essential elements of integrating the model, including it's development and how it was accepted by these nurses. According to the author, the process of changing to this model is dynamic and continuous.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457975 TI - [Motherhood at any price]. AB - What are the real benefits of in-vitro fertilization? (IVF) Does it offer a service to women and couples or does it present itself more as a type of controlled reproduction for which all the consequences are yet unknown? To uncover the answers to these questions, the authors explore the reasons that attract certain women to choose IVF. The authors question if it is appropriate in all infertility cases. They describe IVF including the various stages involved in the process. An overview of the inherent risks and problems with this type of reproductive therapy provide some food for thought. An account of a professional experience illustrates this point. Lucy's story is filled with trials and setbacks. It is the story of a woman exhausted from the IVF process, unhappy, powerless and misunderstood. The nurse is ultimately able to communicate with her. The authors suggest that a "woman's touch" is essential in helping women who are undergoing IVF treatment because of the special comfort and understanding that can be provided to the client. During the IVF process some of the nursing interventions suggested include: using a global approach; providing an empathetic attitude and a reassuring presence; being a good listener; and offering support and encouragement. The nurse must not only create an atmosphere of confidence but should also be able to differentiate between the client's true desire to have a baby and her fantasy of being pregnant. It is essential for the nurse to be able to help the "mother to be" examine and discuss her views and feelings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8457976 TI - Gender differences and bereavement. PMID- 8457978 TI - Antimicrobial susceptibility testing of Neisseria gonorrhoeae and implications for epidemiology and therapy. AB - Antimicrobial susceptibility testing (AST) of Neisseria gonorrhoeae has been under development since the early days of antimicrobial agents. However, it is rarely applied to clinical isolates today. The history of the various in vitro tests to determine the susceptibility of N. gonorrhoeae to antibiotics is rich with evidence that these results predict response to therapy for almost all agents tested. Further, AST is a useful and important aspect of strain characterization and disease epidemiology in conjunction with the more specific but laborious techniques of auxotyping, serotyping, and plasmid analysis. Current technology has overcome many of the objections to AST for N. gonorrhoeae with standardization of test media and the development of an accurate disk diffusion AST method that is suited to most clinical laboratories regardless of volume or level of technical expertise. Ironically, the very low level of resistance to the current primary treatment strategy in the United States, ceftriaxone or another potent cephalosporin, makes the use of AST somewhat superfluous. PMID- 8457979 TI - Unusual infections in humans. AB - Nine cases of unusual infections in humans are presented. In each case, we present the clinical history, histopathologic changes (if indicated), morphologic features of the causative organism, diagnosis, discussion, differential diagnosis, therapy, and current literature. All of the cases are illustrated with pertinent photographs. The nine cases are as follows: (i) acanthocephaliasis, the first acquired human infection by Moniliformis moniliformis in the United States; (ii) dipylidiasis, an uncommon infection caused by the dog tapeworm, Dipylidium caninum; (iii) granulomatous amebic encephalitis, caused by the recently identified leptomyxid group of amebae; (iv) schistosomiasis, a dual infection of the urinary bladder with the rare presentation of both adult worms and eggs of Schistosoma haematobium and Schistosoma mansoni in tissue sections; (v) syphilitic gastritis, an uncommon presentation of Treponema pallidum infection, in a patient with an additional incidental infection by Helicobacter pylori; (vi) microsporidiosis, the only infection caused by a Pleistophora sp. in humans; (vii) sporotrichosis, a rare disseminated infection caused by Sporothrix schenckii with numerous yeast cells in the scrotum; (viii) angiostrongyliasis, the first and only infection caused by Angiostrongylus costaricensis acquired in either Puerto Rico or the United States; and (ix) botryomycosis of the skin and subcutaneous tissue, caused by gram-positive cocci with an unusually large number of granules. PMID- 8457977 TI - Compounds active against cell walls of medically important fungi. AB - A number of substances that directly or indirectly affect the cell walls of fungi have been identified. Those that actively interfere with the synthesis or degradation of polysaccharide components share the property of being produced by soil microbes as secondary metabolites. Compounds specifically interfering with chitin or beta-glucan synthesis have proven effective in studies of preclinical models of mycoses, though they appear to have a restricted spectrum of coverage. Semisynthetic derivatives of some of the natural products have offered improvements in activity, toxicology, or pharmacokinetic behavior. Compounds which act on the cell wall indirectly or by a secondary mechanism of action, such as the azoles, act against diverse fungi but are usually fungistatic in nature. Overall, these compounds are attractive candidates for further development. PMID- 8457982 TI - Breast cancer in African-American women. Review of the literature. AB - Decreased survival rates from breast cancer in the poor and in many African American women are pressing public health problems. Health care providers are challenged to reduce breast cancer deaths in high-risk poor and African-American populations to achieve the National Cancer Institute's goal of reducing cancer deaths 50% by the year 2000. This article presents findings from a review of the literature concerning (a) the disproportionate distribution of cancer deaths in poor and African-American populations compared with non-poor white populations; (b) breast cancer detection initiatives and barriers to health services utilization; (c) primary prevention of breast cancer; and (d) broad strategies to empower poor and African-American women better to control their destiny through enhanced health practices and public policy initiatives. PMID- 8457980 TI - Gram-negative sepsis: a dilemma of modern medicine. AB - Gram-negative sepsis is an increasingly common problem, with up to 300,000 cases occurring each year in the United States alone. Despite the ongoing development of new antibiotics, mortality from gram-negative sepsis remains unacceptably high. To stimulate earlier therapeutic intervention by physicians, a new set of broad definitions has been proposed to define the systemic inflammatory response characteristic of sepsis. In this review, the signs and symptoms of this progressive, injurious process are reviewed and its management is discussed, as are the mechanisms by which bacterial endotoxin triggers the biochemical events that lead to such serious complications as shock, adult respiratory distress syndrome, and disseminated intravascular coagulation. These events often occur even when appropriate antimicrobial therapy has been instituted. An increased understanding of the structure of endotoxin and its role in the development of sepsis, together with advances in hybridoma technology, has led to the development of monoclonal antibodies that bind to endotoxin and significantly attenuate its adverse effects. These agents promise to substantially reduce the morbidity and mortality associated with gram-negative sepsis. PMID- 8457983 TI - Determinants of participation in state-of-the-art cancer prevention, early detection/screening, and treatment trials among African-Americans. AB - It has been suggested that the greatest potential for reducing cancer mortality in high-risk populations may be realized through aggressive implementation of prevention, diagnostic, and state-of-the-art treatment programs and increasing participation in cancer trials. However, the national data suggest that African Americans are most often underrepresented in such programs and/or trials. Multiple factors are assumed to contribute to this situation, but currently few studies have been conducted to validate their influence. A study focused on identifying factors that contribute to participation of African-Americans in investigational cancer programs and/or trials was therefore conducted. Two hundred twenty African-American men and women were recruited to participate in a regional survey. There was evidence to support the impact that perceptions, attitudes, and beliefs have on willingness to participate in investigational programs and/or trials. The factor having the greatest influence on willingness to participate in investigational programs and/or trials was perceived efficacy of the investigational programs and/or trials. Among this sample there was an apparent hesitancy of many to participate in research programs and/or trials. The prevailing belief that such programs and/or trials were only for those with the disease or condition under study appeared to influence their response. However, when provided information on the opportunities for participation in prevention, diagnostic, and treatment programs and/or projects for those within the general community (especially for those at higher risk) and on the benefits of participation, a much greater willingness to participate was expressed by participants. PMID- 8457984 TI - Humor as a nursing intervention. AB - This article describes the use of humor as a nursing intervention and asks if nurses can justify the integration of the use of humor into the repertoire of nursing interventions. Several uses for humor are illustrated, and humor is differentiated from laughter. The article quotes many nurse leaders' opinions about humor and identifies do's and do not's of appropriate humor; it discusses six research studies in which health care professionals used humor as a treatment protocol. The studies were in the areas of preoperative teaching, clinical evaluation, strategies to prevent hopelessness in adolescents with oncologic illness, and group cohesiveness. Results of these six studies give some evidence, although not robust, that humor is an effective intervention. Methods of determining and implementing humor as an appropriate nursing intervention are included. PMID- 8457985 TI - Relaxation training and psychoimmunological status of bereaved spouses. A pilot study. AB - The death of a family member is one of the most stressful and disruptive life events. Although the literature abounds with subjective pieces concerning bereavement, little is known about the complex biological processes that follow in its wake. However, there is a growing body of evidence that psychological distress may compromise immunocompetence and that support strategies may enhance immune function. Our exploratory study examined the influence of relaxation training on the immunological and psychological status (including anxiety and depression) of bereaved spouses. Nine female spouses, all survivors of patients who died from cancer, were recruited from two hospice programs to participate in this relaxation-training program. Standardized psychological instruments and immunological assays were completed at three data-collection points: before the initiation of the relaxation training (approximately 6 weeks after the death of the spouse); at the conclusion of the training; and 4 weeks after the relaxation training. The subjects received a 1-h relaxation-training program weekly for 4 weeks. It included progressive muscle relaxation training and guided imagery supervised by a psychiatric nurse clinical specialist. The results indicated that the relaxation-training program was well-received by the subjects, with promising psychoimmunological trends that merit more rigorous investigation. This exploratory study has demonstrated the feasibility of conducting a relaxation training intervention for bereaved spouses and has laid the foundation for continuing research to study the physiological and psychological responses of the bereaved. PMID- 8457981 TI - Ureaplasma urealyticum intrauterine infection: role in prematurity and disease in newborns. AB - Ureaplasma urealyticum, a common commensal of the urogenital tract of sexually mature humans, is gaining recognition as an important opportunistic pathogen during pregnancy. While its etiologic significance in many aspects of adverse pregnancy remains controversial, recent evidence indicates that U. urealyticum in the absence of other organisms is a cause of chorioamnionitis. Furthermore, ureaplasmal infection of the chorioamnion is significantly associated with premature spontaneous labor and delivery. In at least some cases, it appears to be causal. Present evidence indicates that U. urealyticum is a cause of septicemia, meningitis, and pneumonia in newborn infants, particularly those born prematurely. There is strong but not definitive evidence that ureaplasmal infection of the lower respiratory tract can lead to development of chronic lung disease in very low-birth-weight infants. Although risk factors for colonization of the lower genitourinary tract have been identified, little information is available concerning risk factors for intrauterine infection and host immune responses to invasive infection. Recent establishment of animal models of respiratory and central nervous system diseases should provide an opportunity to evaluate risk factors, pathogenic mechanisms, and operative immune mechanisms. However, the most critical need is additional information concerning indications for diagnosis and treatment as well as efficacy of treatment. PMID- 8457986 TI - Improving ambulatory oncology nursing practice. An innovative educational approach. AB - To meet the educational needs of ambulatory oncology nurses, an innovative and flexible program was created at a major cancer institute in Canada. Utilizing adult learning principles, standards of nursing practice, and departmental goals, the Clinical Nurse Specialists and Clinical Teachers creatively approached the need for extensive education. Five site specific educational workshops were provided to the nursing staff utilizing a self-directed learning style to capture the varied experiences, educational background, and motivations of the staff. This paper highlights the necessary program elements, implementation of, and evaluation of the educational program. PMID- 8457987 TI - Declarations concerning AIDS. PMID- 8457988 TI - Biblical perspectives on AIDS. PMID- 8457989 TI - Could you be a 'buddy'? PMID- 8457990 TI - Preparing for death--embracing life. PMID- 8457991 TI - Your judgmental attitudes. PMID- 8457992 TI - HIV and AIDS--a Christian response. PMID- 8457993 TI - Oligosaccharide microscale analysis by circular dichroic spectroscopy: reference spectra for chromophoric D-fructofuranoside derivatives. AB - The microscale analytical method that is being developed in this group for the structure determination of oligosaccharides yields monosaccharide derivatives bearing two types of chromophores suitable for exciton-coupling, namely, 4 bromobenzoate (lambda max 245 nm) and 4-methoxycinnamate (lambda max 311 nm). Comparison of the circular dichroic (CD) curves of these subunits to those in the reference library allows for the determination of the sugar identities, linkage positions, and the absolute configurations. The 32 possible derivatives of methyl alpha- and beta-D-fructofuranosides bearing four chromophores were prepared and their CD spectra recorded. These data serve to extend the CD library, which already encompasses pyranoside derivatives with the gluco-, galacto-, and manno configurations, and extend the utility of this methodology to the analysis of fructose-containing oligosaccharides. PMID- 8457994 TI - Rapid production of a panel of blood group A-active oligosaccharides using chemically synthesized di- and tri-saccharide primers and an easily prepared porcine (1-->3)-alpha-N-acetyl-D-galactosaminyltransferase. AB - A porcine (1-->3)-alpha-N-acetyl-D-galactosaminyltransferase was obtained in a state suitable for preparative-scale (mg-scale) synthesis using simple procedures requiring only three days of effort. The enzyme thus prepared transferred GalNAc efficiently from UDP-GalNAc to six different chemically synthesized di- and tri saccharide H-active structures to yield blood-group A-active oligosaccharides that were characterized by 1H NMR spectroscopy and mass spectrometry. This work further demonstrates the efficiency and attractiveness of using glycosyltransferases in a combined chemoenzymatic approach for the rapid production of biologically active oligosaccharides. PMID- 8457995 TI - An improved synthesis of 4-azido-4-deoxy- and 4-amino-4-deoxy-alpha,alpha trehalose and their epimers. AB - The order of esterification of the eight hydroxyl groups of alpha,alpha-trehalose is HO-6.6' > HO-2.2' > HO-3.3' > HO-4.4'. Under the appropriate conditions of benzoylation, the heptabenzoate with HO-4' free was obtained in good yield (58%), along with the octabenzoate and the hexabenzoate having HO-4.4' free. The readily isolated heptabenzoate was a convenient starting material for the synthesis of 4 azido-4-deoxy- (84%) and 4-amino-4-deoxy-alpha-D-galactopyranosyl alpha-D glucopyranoside, and the heptabenzoate of alpha-D-galactopyranosyl alpha-D glucopyranoside with HO-4' free, which was used as a synthetic precursor of 4 azido-4-deoxy-alpha-D-glucopyranosyl alpha-D-glucopyranoside and its amino analogue. PMID- 8457996 TI - Separation of hyaluronan oligosaccharides by the use of anion-exchange HPLC. PMID- 8457997 TI - Synthesis of an intermediate fragment of the capsular polysaccharides of Klebsiella type 8. PMID- 8457998 TI - Synthesis of beta-estradiol beta-D-xylopyranosides, primers of heparan sulfate in Chinese hamster ovary cells. PMID- 8457999 TI - Synthesis of methyl 3-O-(2-O-methyl-alpha-L-fucopyranosyl)-alpha-L rhamnopyranoside, methyl 3-O-alpha-L-rhamnopyranosyl-alpha-D-glucopyranoside, and methyl 3-O-[3-O-(2-O-methyl-alpha-L-fucopyranosyl)-alpha-L-rhamnopyranosyl]-al pha-L-rhamnopyranoside: di- and tri-saccharide segments of a lipo-oligosaccharide (LOS-1) of Mycobacterium szulgai. PMID- 8458000 TI - An enzyme-linked immunosorbent assay for blood-group A and B enzymes. PMID- 8458001 TI - Overlapping anomeric effects in a sucrose analogue. AB - Previous calculations with the molecular mechanics program MM3 gave unusually high energies (as much as 5.5 kcal/mol) for sucrosyl geometries found in single crystal diffraction studies of oligosaccharides. Comparable MM3 energies for observed interresidue linkage conformations of disaccharides such as maltose and cellobiose are all within 2.8 kcal/mol. These results suggest that some energies calculated by MM3 for the linkage between anomeric centers of a pyranose ring and a furanose ring are too high. In the present paper, ab initio calculations at the 4-21G level and MM3 were used to study the conformational energies and geometry of a sucrose analogue, tetrahydro-2-[(tetrahydro-2-furanyl)oxy]-2H-pyran. The range of energies of the observed structures was substantially reduced (to 2.4 kcal/mol) with the 4-21G calculations for the analogue despite an increase for the analogue (to 7.5 kcal/mol) based on new MM3 calculations. Besides the improved energy values, the 4-21G calculations also reproduced the observed variations in the endocyclic C-O bond lengths better than did MM3. PMID- 8458002 TI - Enhanced structural information on oligosaccharides by scan of linked magnetic and electrostatic fields (B/E) and neutral gas collision fast-atom-bombardment mass spectrometry (FABMS). AB - Homo- and hetero-oligosaccharides 1-27, composed of hexopyranose, deoxyhexopyranose, deoxyfluorohexopyranose, and 2-acetamido-2-deoxyhexopyranose units, have been examined by fast-atom-bombardment mass spectrometry. Scans by linked magnetic and electrostatic (B/E) fields of quasi-molecular [M+H] ions, or scans combined with helium collision, gave rise to structurally significant ions. The information thus obtained aids significantly in the sequence analysis of oligosaccharides without derivatization. PMID- 8458003 TI - Synthesis of the C'D' disaccharide of aureolic acid. AB - Arylbis(arylthio)sulfonium salts have been used to activate glycals towards nucleophilic addition to form principally 2-deoxy-beta-glycosides. This method was applied to the synthesis of the 2-(methylphenylthio)-2'-phenylthio derivative (22) of methyl O-(4-O-benzyl-2,6-dideoxy-beta-D-arabino- hexopyranosyl)-(1-->3) 3,4-di-O-benzyl-2,6-dideoxy-2,6-beta-D-arabino- hexopyranoside, the C'D' ring analog of an aureolic acid disaccharide. The condensation of 1,5-anhydro-2,6 dideoxy-D-arabino-hex-1-enitol with methanol in the presence of the phenylbis(phenylthio)sulfonium salt resulted in formation of the first beta glycoside linkage. The methyl 6-deoxyglucoside obtained was deprotected at HO-3 to give the 2-thiophenyl-substituted 2,6-dideoxy-beta-glucoside. This was coupled with 1,5-anhydro-3,4-di-O-benzyl-2-deoxy-D-arabino-hex-1-enitol in the presence of 4-methylphenyl[bis(4-methylphenyl)thio]sulfonium salt to give the (1-->3) linked disaccharide 22. Finally, desulfurization of 22 using WII Raney nickel generated the required 2,2'-dideoxydisaccharide. PMID- 8458004 TI - The structure of an antigenic glycolipid (SL-IV) from Mycobacterium tuberculosis. AB - The structure of an antigenic glycolipid isolated recently from cell walls of various strains of Mycobacterium tuberculosis and believed to be a sulfolipid consisting chiefly of 2,3-di-O-(hexadecanoyl/octadecanoyl)-alpha,alpha-trehalose 2'-sulfate (designated as SL-IV), was reinvestigated by mass spectrometry and nuclear magnetic resonance spectroscopy. The material proved to be a complex mixture of closely related components which are indeed 2,3-di-O-acyltrehaloses. However, no sulfate group was found in the antigen, and revision of its designation as a sulfolipid is therefore required. The lipid substituents comprise an estimated 20% of C14-C19 fatty acids, including tetradecanoic (myristic), 9-tetradecenoic (myristoleic), 9-hexadecenoic (palmitoleic), 9 octadecenoic (oleic), 10-methylhexadecanoic (tuberculopalmitic), and 10 methyloctadecanoic (tuberculostearic) acids in addition to hexadecanoic (palmitic) and octadecanoic (stearic) acids, and approximately 80% of higher, methyl-branched acids. Among the latter are, principally, 2,4-dimethyldocosanoic and 3-hydroxy-2,4,6- trimethyltetracosanoic acids, and a smaller proportion of 2,4,6-trimethyltetracos-2-enoic acid. Numerous further acids, related to those mentioned by methylene homology, are also present in small proportions. PMID- 8458005 TI - Synthesis, conformational analysis, and the glycosidic coupling reaction of substituted 2,7-dioxabicyclo[4.1.0]heptanes: 1,2-anhydro-3,4-di-O-benzyl-beta-L- and beta-D-rhamnopyranoses. AB - 1,2-Anhydro-3,4-di-O-benzyl-alpha-L-rhamnopyranose was synthesized from L rhamnose, while the D-enantiomer was synthesized from methyl 6-deoxy-2,3-O isopropylidene-alpha-D-mannopyranoside. For both of the syntheses, the key intermediates were 2-O-acetyl-3,4-di-O-benzyl-alpha-D- and -alpha-L rhamnopyranosyl chlorides that were quantitatively prepared from the corresponding diacetates by chlorination. Ring closure of the chlorides was carried out readily with potassium tert-butoxide in oxolane, and crystalline 1,2 anhydro-3,4-di-O-benzyl-beta-D- and beta-L-rhamnopyranose were obtained in high yields. Conformational calculations, which were carried out using vicinal proton proton coupling constants by the modified Karplus equation, suggested that the conformations of the pyranose rings of the title compounds were basically a half chair (4H5) with some flattening at C-4. Force-field calculations (MMP2) confirmed the experimental conformation with good agreement. The coupling reaction of the 1,2-anhydro-L-rhamnose ether with 1,2;3,4-di-O-isopropylidene alpha-D-galactopyranose was effected in oxolane by catalysis by a Lewis acid, and only the alpha-linked disaccharide was obtained. PMID- 8458006 TI - Syntheses and insulin-like activity of phosphorylated galactose derivatives. AB - The syntheses of the poly-phosphorylated galactosides 6, 8, 10, 13, 16, and 20, isolated as sodium salts, have been performed. The non-phosphorylated disaccharide 17 and trisaccharide 21 have been prepared via glycosylation of the 2-(trimethylsilyl)ethyl galactosides 3 and 2, respectively, and subsequent complete deprotection. Preliminary insulin-like activity of the phosphorylated derivatives is reported. PMID- 8458007 TI - Bile alcohol glucuronides: regioselective O-glucuronidation of 5 beta-cholestane 3 alpha,7 alpha,12 alpha,25-tetrol and 24-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol. AB - A facile and regiocontrolled procedure for the preparation of 5-beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol-3-O-beta-D-glucuronide and its corresponding C 26 analogue is described. The method involves direct coupling of bile alcohols, namely, 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol and 24-nor-5 beta cholestane-3 alpha,7 alpha,12 alpha,25-tetrol to methyl (tetra-O-acetyl-beta-D glucopyranuronate) in the presence of a Lewis acid, tin(IV) chloride, in dichloromethane. The resulting anomeric pairs of 1,2-trans- and 1,2-cis glucuronides of tetrols were resolved by analytical and preparative thin-layer chromatography, and their identities were established by high-resolution 1H NMR spectroscopy and by chemical-ionization and fast-atom-bombardment mass spectrometry. The method described has a practical advantage over the traditional two-step synthesis involving bromides as it is more efficient and uses inexpensive and less toxic materials. It is suggested that these compounds will be useful for studying permeability of the blood-brain barrier in cerebrotendinous xanthomatosis (CTX). PMID- 8458008 TI - Synthesis of 4-O- and 6-O-monoacryloyl derivatives of sucrose by selective hydrolysis of 4,6-O-(1-ethoxy-2-propenylidene) sucrose. Polymerization and copolymerization with styrene. AB - The synthesis of an ethylenic orthoester of sucrose by transorthoesterification of an acrylic reagent with sucrose is described. Mild hydrolysis of this orthoester gave sucrose selectively monosubstituted by an acryloyl group at either the 4-O- or the 6-O-position. These acrylates were homopolymerized and copolymerized with styrene, and the corresponding polymers were characterized. PMID- 8458009 TI - Biosynthesis of curdlan from culture media containing 13C-labeled glucose as the carbon source. AB - 13C-Labeled curdlans were biosynthesized by Agrobacterium sp. (ATCC 31749) from culture media containing D-(1-13C)glucose, D-(6-13C)glucose, or D-(2-13C)glucose as the carbon source, and their structures were analyzed by 13C NMR spectroscopy. The labeling was mainly found in the original position, that is, C-1, C-6, or C 2, indicating direct polymerization of introduced glucose. In addition, C-3 in curdlan obtained from D-(1-13C)glucose, C-1 in curdlan obtained from D-(6 13C)glucose, and C-1 and C-3 in curdlan obtained from D-(2-13)glucose were labeled. From analysis of this labeling, the biosynthesis of curdlan was interpreted as involving five routes: (1) direct synthesis from glucose; (2) rearrangement (1-13C-->3-13C); and (3) isomerization (6-13C-->1-13C) of cleaved trioses by the Embden-Meyerhof pathway, followed by neogenesis of glucose and formation of curdlan; (4) from fructose 6-phosphate formed in the pentose cycle (2-13C-->1-13C, 3-13C); and (5) neogenesis of glucose from fragments produced in various pathways of glycolysis. The 13C-labeling at C-6 and C-2 in the starting glucoses is well preserved in the C-6 carbon and the C-1 to C-3 carbons, respectively, in the curdlan produced. PMID- 8458010 TI - Synthesis and spectroscopic characterization of hydroxycinnamoylated methyl alpha L-arabinofuranosyl-(1-->2)- and (1-->3)-beta-D-xylopyranosides. AB - A reaction sequence for the preparation of methyl 5-O-feruloyl-alpha-L- arabinofuranosyl-(1-->3)-beta-D-xylopyranoside, the companion 5-O-p-coumaroyl disaccharide, and their (1-->2) analogs has been developed. The (1-->3) hydroxycinnamoylated disaccharides are available in 11 steps from L-arabinose and methyl beta-D-xylopyranoside in 17% overall yield (based on methyl beta-D xylopyranoside). The corresponding (1-->2) materials were prepared in 9 steps in > 37% overall yield. Complete spectral characterization provides unambiguous assignments for comparison with analogous materials isolated from plant cell walls. Conformational aspects of the prepared materials are discussed in relation to coupling-constant information. PMID- 8458011 TI - Standardized intermediates for oligosaccharide synthesis. A convenient preparation of partially protected derivatives of allyl O-beta-D-galactopyranosyl (1-->4)-beta-D-glucopyranoside suitable for chain extension at position O-4'. PMID- 8458012 TI - Synthesis of low-toxicity, 5-deoxy-5-fluoro and 5-deoxy-5,5-difluoro derivatives of arbekacin and its analogs, and study of structure-toxicity relationships. PMID- 8458013 TI - Synthesis of cyclophosphamide analogs from aminotrideoxy sugars. PMID- 8458014 TI - The crystal and molecular structure of the trisaccharide erlose as the monohydrate. AB - Erlose [O-beta-D-fructofuranosyl-(1-->2)-O-alpha-D-glucopyranosyl-(1-->4)- alpha D-glucopyranoside] monohydrate, C18H32O16.H2O, M(r) = 522.45, is orthorhombic, P2(1)2(1)2(1) with a = 30.748 (3), b = 8.757 (1), c = 8.270 (1) A, and Z = 4. The structure was solved by direct methods, and refined to R = 0.048 for 1909 observed reflections. The torsion angles about the (1-->2) and (1-->4) glycosidic bonds are similar to those observed in other sucrose- and maltose-like oligosaccharides. The maltose moiety has an O-3'-H...O-2 intramolecular hydrogen bond, but the sucrose moiety has no intramolecular hydrogen bonds. The hydrogen bonding in the crystal includes infinite and finite chains crosslinked by the water molecule. PMID- 8458015 TI - The application of NMR-pattern-recognition methods to the classification of reduced, peracetylated oligosaccharide residues. AB - In the present paper homo- and hetero-nuclear correlation spectroscopies have been used to assign proton and carbonyl carbon resonances of a number of reduced, peracetylated mono- and oligo-saccharide derivatives. Each of the native structures for which assignments were made represent residues or substructures typically found in N- or O-linked glycans. Using the assigned NMR parameters as a basis, residues contained in parent structures were classified according to their residue type and glycosidic substitution sites using a relatively simple K Nearest Neighbor pattern recognition approach. The method was able to correctly assign 99% of 77 "test residues" to their correct structural class using the full set of 19 assigned parameters as a basis. Similar correlations made between data and structure were less successful when reduced variable sets selected on the basis of SIMCA optimization were used. PMID- 8458016 TI - Structural characterization and rheological properties of an extracellular glucuronan produced by a Rhizobium meliloti M5N1 mutant strain. AB - The mutant strain M5N1 C.S. (NCIMB 40472) of Rhizobium meliloti M5N1 is able to produce during fermentation a partially acetylated extracellular (1-->4)-beta-D glucuronan. At low concentration (1 g.l-1), in the presence of monovalent cations, this new glucuronate behaves as a thickening agent, whereas at higher concentration a thermoreversible gel is obtained. With such divalent cations as Ca2+, a thermally stable gel can be formed. PMID- 8458017 TI - Fluorinated carbohydrates as potential plasma membrane modifiers. Synthesis of 3 deoxy-3-fluoro derivatives of 2-acetamido-2-deoxy-D-hexopyranoses. AB - Treatment of benzyl 2-acetamido-4,6-O-benzylidene-2-deoxy-alpha-D-allopyranoside with diethylaminosulfur trifluoride or of the 3-O-mesyl derivative with tetrabutylammonium fluoride gave the 2,3-unsaturated compound instead of the expected 3-deoxy-3-fluoro derivative. The latter was obtained when benzyl 2 acetamido-4,6-di-O-benzyl-2-deoxy-3-O-mesyl-alpha-D-allopyran oside was treated with potassium fluoride. Methyl 2-azido-4,6-O-benzylidene-2-deoxy-alpha-D altropyranoside was converted into the 2-acetamido- and 2-phthalimido-3-O-mesyl derivatives; when treated with fluoride nucleophile, these gave only the 2,3 aziridine derivative. However, treatment of the 2-azido-2-deoxy derivative with diethylaminosulfur trifluoride gave methyl 2-azido-2,3-dideoxy-3-fluoro-alpha-D mannopyranoside which, after reduction, deprotection, and acetylation, gave the acetylated derivative of methyl 2-acetamido-2,3-dideoxy-3-fluoro-alpha-D mannopyranoside in excellent yield. These acetylated 3-fluoro derivatives exhibited inhibition of cell growth of murine L1210 leukemia cells in culture at micromolar concentrations. PMID- 8458018 TI - The preparation and susceptibility to hydrolysis of novel O-galacturonoyl derivatives of carbohydrates. AB - D-Galacturonic acid or (1-->4)-alpha-D-galacturonan reacted in aqueous pyridine in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide with alcohols to yield esters. The alcohols that gave high yields of D-galacturonoyl derivatives were primary and included methanol, ethanol, 1-propanol, D-glucose, D-galactose, methyl beta-D-glucopyranoside, methyl beta-D-galactopyranoside, and cellulose. D Galacturonic acid itself readily gave an O-D-galacturonoyl-D-glacturonic acid. The proposed structure of one compound, methyl 6-O-D-galacturonoyl-beta-D glucopyranoside, was supported by 1H and 13C NMR data and the FAB mass-spectral data. Each ester was hydrolysed at pH 11 and 25 degrees C within 1 h. O-D Galacturonoyl-D-glucose was considerably more alkali labile than O polygalacturonoyl-D-glucose, and O-D-galacturonoylcellulose had an intermediate stability. The esters were relatively stable to cold acid, but could be hydrolysed by M trifluoroacetic acid at 100 degrees C for 1 h. The esters tested were resistant to digestion by 'Driselase', although the glycosidic bonds of O polygalacturonoyl-D-glucose were hydrolysed to yield O-oligogalacturonoyl-D glucoses of low molecular weight. The possible application of these analytical methods to the detection of O-uronoyl-type cross-links in cell-wall polysaccharides is discussed. PMID- 8458019 TI - Homologous sensitisation of embryonic chick atrial myocytes to adenosine: mediation by adenosine A1 receptor and guanine nucleotide binding protein. AB - OBJECTIVE: The aim was to characterise the process and the mechanisms of sensitisation of the atrial myocyte to adenosine receptor agonist. METHODS: The ability of adenosine A1 receptor to mediate inhibition of adenylyl cyclase activity and myocyte contractility was determined in atrial myocytes cultured from 14 d chick embryos. Under conditions in which the myocytes were sensitised to the effects of A1 agonist, changes in the levels of adenosine A1 receptor and pertussis toxin sensitive G proteins were determined and correlated with alterations in the adenylyl cyclase activity and contractile responses of the myocyte to the A1 agonist. RESULTS: Removal of adenosine from the culture medium with adenosine deaminase resulted in an enhanced ability of the adenosine A1 receptor agonist R-N6-(2-phenylisopropyl)-adenosine to exert a direct, negative inotropic effect and to inhibit isoprenaline stimulated adenylyl cyclase activity. The increase in the extent of maximum inhibition of adenylyl cyclase activity and of myocyte contractility was 215(30), n = 5, and 90(10)%, n = 14, respectively. Binding of the antagonist radioligand [3H]-8-cyclopentyl-1,3 dipropylxanthine in membranes from myocytes pre-exposed to adenosine deaminase showed a 70% increase in the adenosine A1 receptor density and a 54% increase in the proportion of the high affinity adenosine A1 receptor: control 33(5)%, n = 5, versus sensitised 49(3)%, n = 5, p < 0.01. The increase in the total number of adenosine receptors and the proportion of the high affinity form was associated with a similar increase in the level of pertussis toxin sensitive G protein(s), as determined by pertussis toxin mediated 32P-ADP ribosylation and by immunoblotting. Prior exposure of the culture to the adenosine receptor antagonist 8-(p-sulphophenyl)theophylline also led to similar results. CONCLUSIONS: The data indicate that the increased level of pertussis toxin sensitive G protein(s) results in an enhanced coupling to form the high affinity adenosine A1 receptor, that newly formed high affinity receptors are linked to an enhanced sensitivity of atrial myocytes to A1 adenosine agonist stimulation, and that upregulation of the G protein is a mechanism mediating the homologous sensitisation of cardiac adenosine A1 receptor pathway. PMID- 8458020 TI - Role of nucleoside transport inhibition and endogenous adenosine in prevention of catecholamine induced death in rabbits. AB - OBJECTIVE: R 75,231, a potent and specific nucleoside transport inhibitor, largely prevents cardiac damage and death in catecholamine challenged rabbits. The major biochemical effect of nucleoside transport inhibition in ischaemic and reperfused myocardium is a prolonged accumulation of adenosine. The cardioprotection by R 75,231 may be explained if it can be shown that endogenous adenosine plays a role in catecholamine cardiotoxicity and if nucleoside transport inhibition is required for the cardioprotective effect of R 75,231. METHODS: Several groups of rabbits were infused with catecholamines until death. Changes in survival with time of infusion by coinfusion of aminophylline and/or treatment with R 75,231 and its two stereoenantiomers were assessed. RESULTS: Treatment with R 75,231 postponed the time to reach 50% mortality threefold after challenge with adrenaline or noradrenaline. Draflazine, the (-)-enantiomer of R 75,231, was also effective, whereas the (+)-enantiomer, which is devoid of any effect on the transporter, was not cardioprotective. The cardioprotective effect of R 75,231 was dependent on the extent and duration of ex vivo inhibition of the transporter in blood. Co-infusion of aminophylline with adrenaline significantly accelerated the rate of mortality. CONCLUSIONS: Nucleoside transport inhibition is the major, if not the only, determinant for efficacy of R 75,231 and draflazine as cardioprotective agents. Taken together with the evidence for a role of endogenous adenosine, the benefit from nucleoside transport inhibition in this model may be the result of prolonged accumulation of endogenous adenosine. PMID- 8458021 TI - Acadesine lowers temporal threshold for the myocardial infarct size limiting effect of preconditioning. AB - OBJECTIVE: The aim was to test the hypothesis that adenosine A1 receptor activation triggers the cardioprotective effects of ischaemic preconditioning, by determining whether pretreatment with acadesine (5-amino-4-imidazolecarboxamide riboside), an agent which increases cardiac adenosine level during ischaemia, could alter the threshold for preconditioning. METHODS: A branch of the left coronary artery of rabbit hearts was occluded for 30 min and reperfused for 3 h. Infarct size and risk zone size were determined with tetrazolium and fluorescent particles, respectively. Four groups were studied: untreated controls, a group which was pretreated with acadesine (2.5 mg.kg-1.min-1 for 5 min followed by 0.5 mg.kg-1.min-1 for 30 min ending 10 min prior to ischaemia), a group which was preconditioned with 2 min coronary branch occlusion + 10 min reperfusion, and a group which received pretreatment with acadesine prior to 2 min ischaemic preconditioning. RESULTS: Percent infarction, normalised as a percentage of the ischaemic zone, in the 2 min preconditioning group was 43.2(SEM 5.1)% which was not different from control [40.2(3.5)%]. Two minutes of preconditioning was not long enough to confer the cardioprotective effect of preconditioning. Acadesine alone had no protective effect on infarct size [38.5(4.5)%], but acadesine + 2 min preconditioning significantly limited infarction [18.1(2.7)%; p < 0.01]. CONCLUSIONS: Acadesine lowered the threshold for preconditioning in the rabbit to below 2 min of ischaemia. This observation supports the theory that endogenous adenosine which accumulates during the preconditioning ischaemia mediates the protective effects, and that this response can be augmented by acadesine. PMID- 8458022 TI - Intravenous adenosine suppresses cardiac release of endothelin after myocardial ischaemia and reperfusion. AB - OBJECTIVE: Intravenous adenosine decreases infarct size in experimental models of myocardial ischaemia/reperfusion. Ischaemia/reperfusion is associated with a significant increase in cardiac release of endothelin. The effect of cardioprotective doses of adenosine on endothelin release was explored in dogs undergoing 90 min coronary occlusion and 210 min reperfusion. METHODS: Dogs were assigned to intravenous adenosine in a dose of 0.15 mg.kg-1.min-1 (n = 12) or control (n = 11) during the first 150 min reperfusion. Serial endothelin levels were obtained from the coronary sinus and aortic blood and measured by radioimmunoassay. RESULTS: Adenosine significantly reduced infarct size expressed as a percent of the risk region (28.8 6% v 14.4 2%; p = 0.03). A similar increase in aortic and coronary sinus blood endothelin was observed in both groups during temporary occlusion. A significant transcardiac increase in endothelin levels was present in the control group 60 min after reperfusion whereas no increase occurred in the adenosine treated group [control 5.6(SEM 1.9) v adenosine 0.2(1.4) pg.ml-1; p = 0.02]. Similarly, intravenous adenosine tended to prevent the increase in myocardial endothelin production seen in control animals during the early reperfusion period [control 280(146) v adenosine -57(55) pg.min-1; p = 0.05]. Endocardial blood flow in the ischaemic zone 210 min after reperfusion was significantly higher in the adenosine group, at 0.60(0.02) v 0.38(0.02) ml.min 1.g-1; p < 0.05. A significant correlation between endothelin levels, endocardial flow and infarct size was observed in the control group 3 h after reperfusion: r = 0.73, p = 0.02; r = 0.62, p = 0.03 respectively. This relationship was absent in animals treated with adenosine. CONCLUSIONS: Intravenous adenosine suppresses the release of endothelin from the previously ischaemic myocardium during the early reperfusion period. This effect may in part contribute to the improvement by adenosine in postischaemic microcirculatory flow resulting in attenuation of the "no reflow" phenomenon. PMID- 8458023 TI - Effect of selective A1 adenosine receptor antagonism of postdefibrillation cardiovascular depression: evidence for an antiadrenergic role of endogenous adenosine. AB - OBJECTIVE: The aim was to examine the effect of a selective A1 adenosine receptor antagonist (N-0861) on postdefibrillation cardiovascular depression to determine whether antagonist mediated enhanced postdefibrillation haemodynamic recovery is due to reversal of the antiadrenergic action of adenosine, an A1 receptor mediated effect. METHODS: Halothane-nitrous oxide anaesthetised Duroc pigs of either sex, weight 22-25 kg, were subjected to sequential episodes of induced ventricular fibrillation lasting either 15 s (terminated by a suprathreshold shock at 60-70 A) or 35 s (subjected to a subthreshold shock at 20 A followed by a suprathreshold shock at 60-70 A) during intravenous placebo infusion (n = 10), N-0861 infusion (0.1 mg.kg-1.min-1, n = 10), and N-0861 infusion plus propranolol (2 mg.kg-1, n = 6). RESULTS: N-0861 significantly enhanced immediate postdefibrillation electrophysiological and haemodynamic recovery compared to placebo for ventricular fibrillation episodes lasting 35 s. Over the first 15 s postdefibrillation, N-0861 significantly (p < 0.05) shortened mean cycle length by 55%, increased mean arterial pressure by 33%, and increased the first derivative of left ventricular pressure (an indirect measure of cardiac contractility) by 100% compared to placebo. At 60 s postdefibrillation, when other variables were equal, the first derivative of left ventricular pressure in the presence of N-0861 remained 26% greater than placebo. This effect was completely antagonised by propranolol. CONCLUSIONS: (1) Cardiac contractility in the immediate postdefibrillation period is suppressed by the antiadrenergic action of endogenous adenosine. (2) Selective A1 adenosine receptor antagonism can markedly enhance postdefibrillation contractility. (3) These results support an antiadrenergic role of endogenous adenosine under pathophysiological conditions. PMID- 8458024 TI - Endogenous adenosine, A1 adenosine receptor, and pertussis toxin sensitive guanine nucleotide binding protein mediate hypoxia induced AV nodal conduction block in guinea pig heart in vivo. AB - OBJECTIVE: The aim was to study the mechanism of global hypoxia induced atrioventricular (AV) nodal conduction block in vivo using a guinea pig model. METHODS: Animals subjected to 10 min periods of global hypoxia, induced by decremental changes in O2 content in the inhaled gas mixture, were randomly divided into three groups: group I = control; group II = animals treated with a new selective A1 adenosine receptor antagonist, N0861 (N6-endo-norbornan-2-yl-9 methyladenine); and group III-animals treated with pertussis toxin, an irreversible inhibitor of specific guanine nucleotide binding proteins (G protein). RESULTS: Progressive incremental hypoxia was associated with progressive AV nodal conduction delay culminating in a complete block. In addition, there was an inverse relationship between the severity of hypoxia and time to AV nodal block. Both N0861 and pertussis toxin treatment significantly reduced the degree of hypoxia induced AV nodal conduction block and delayed its appearance. CONCLUSIONS: (1) Endogenous adenosine released during acute global hypoxia causes AV nodal conduction block observed under these conditions in the guinea pig heart in vivo; and (2) this action of adenosine in the AV node is mediated by an A1 adenosine receptor and a pertussis toxin sensitive G protein. PMID- 8458025 TI - Oxygen free radicals, reperfusion injury, endothelial cells, and von Willebrand factor. PMID- 8458026 TI - Adenosine--a cardioprotective and therapeutic agent. PMID- 8458027 TI - Adenosine enhanced preservation of myocardial function and energetics. Possible involvement of the adenosine A1 receptor system. PMID- 8458028 TI - Adenosine and the anti-infarct effects of preconditioning. PMID- 8458029 TI - Infarct size limitation by preconditioning: its phenomenological features and the key role of adenosine. PMID- 8458030 TI - Acadesine: the prototype adenosine regulating agent for reducing myocardial ischaemic injury. AB - Acadesine is the prototype of a new class of therapeutic compounds termed adenosine regulating agents. Acadesine is pharmacologically silent in normal circumstances, but its activity becomes operative during situations of net ATP catabolism, when it increases local adenosine levels. Thus acadesine is able to harness the beneficial effects of this protective autacoid without the limiting side effects associated with using adenosine itself or an adenosine mimetic or transport inhibitor. The demonstrated efficacy of acadesine in various models of myocardial ischaemia and the preliminary clinical results 48 indicate that acadesine and other ARAs could represent important new additions to the cardiologist's armamentarium to combat myocardial ischaemia and its sequelae. PMID- 8458031 TI - Effect of adenosine on coronary blood flow and its use as a diagnostic test for coronary artery disease. AB - Myocardial perfusion imaging during adenosine induced coronary hyperaemia is a highly sensitive method for diagnosing coronary artery disease. Most perfusion defects reflect heterogeneity in coronary blood flow in the territories of normal and diseased coronary arteries. Myocardial ischaemia can occur, however, due to subendocardial hypoperfusion and coronary artery steal. Evidence for myocardial ischaemia is more difficult to document in clinical than in experimental studies, and includes abnormalities in the ST segment, wall motion, haemodynamic variables, metabolism, and coronary blood flow responses. Using these indices, myocardial ischaemia may occur in some patients with coronary artery disease but it is not a prerequisite for the development of perfusion abnormalities and for the diagnosis of coronary artery during adenosine stress testing. PMID- 8458032 TI - Cardiac electrophysiology and pharmacology of adenosine: basic and clinical aspects. PMID- 8458033 TI - Cloned receptors and cardiovascular responses to adenosine. AB - Four subtypes of adenosine receptors have recently been cloned from thyroid, brain and testis. In this review we have summarised properties of these purinergic receptors. The cloned A1 and A2 subtypes are probably similar or identical to receptors that exist on cardiac and vascular tissues, respectively. A comparison of the amino acid sequences of A1, A2a, and A2b receptors reveals several stretches of conserved amino acids that are unique to adenosine receptors, primarily in the membrane spanning regions. Species differences in A1 receptors indicate that minor changes in receptor structure can produce marked changes in ligand binding properties and may facilitate the identification of amino acids involved in ligand recognition. A confusing A1 receptor subclassification system of putative A1a, A1b, and A3 subtypes has emerged based on subtle rank order potency differences for various ligands among tissues. cDNAs corresponding to these A1 subtypes have not yet been isolated. Atrial A1 receptors activate K+ channels and inhibit adenylyl cyclase. These two pathways appear to be independently up and down regulated, suggesting the existence either of atrial A1 receptor subtypes or of differential regulation of the coupling of a single receptor to distinct GTP binding proteins. An adenosine receptor distinct from A1 and A2 receptors has been cloned from testis and designated TGPCR, or A3, although it differs from the pharmacologically defined A3 receptor. We suggest that the current A1/A3 receptor subtype nomenclature be abandoned and superseded by a nomenclature based solely on receptor cDNAs. In addition to the cloned adenosine receptors, a novel A4 subtype has been proposed based on pharmacological and electrophysiological criteria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458034 TI - Nucleoside transport inhibition: a therapeutic approach to cardioprotection via adenosine? PMID- 8458035 TI - Is adenosine an endogenous myocardial protective (antiarrhythmic) substance under conditions of ischaemia? PMID- 8458036 TI - Effects of R-PIA, a selective A1 adenosine agonist, on haemodynamics and ischaemic arrhythmias in pigs. AB - OBJECTIVES: Adenosine has previously been shown to protect against ischaemia induced ventricular arrhythmias. The aim of this study was to determine whether stimulation of A1 adenosine receptors with a selective agonist also protects against arrhythmias, and to attempt to elucidate the underlying mechanisms. METHODS: Large White/Welsh Landrace cross breed domestic pigs (25-40 kg) subjected to left anterior descending coronary artery occlusion were used. R-PIA [R(-)N6-(2-phenylisopropyl) adenosine; 5 micrograms.kg-1] was given prior to coronary artery occlusion and the effects on haemodynamic variables and early ischaemic arrhythmias in the absence and presence of right atrial pacing were studied. The three experimental groups were: solvent controls, n = 10; R-PIA without pacing, n = 10; R-PIA with atrial pacing, n = 10. Ex vivo assessment of platelet aggregation was also performed to determine any inhibitory effects of R PIA on platelets. RESULTS: Administration of R-PIA without atrial pacing reduced the total number of ventricular ectopic beats induced by coronary occlusion, from 326(SEM 71) in controls to 121(30) (p < 0.05) and the incidence of ventricular fibrillation from 70% to 20% (p < 0.05). At the dose used, R-PIA reduced heart rate from 102(7) to 74(3) beats.min-1, with a consequent reduction in mean arterial blood pressure from 95(4) to 81(3) mm Hg. Atrial pacing following drug administration, at a rate of 109(5) beats.min-1, restored blood pressure and abolished the antiarrhythmic effects of R-PIA. Drug intervention had no effect on either ex-vivo platelet aggregation or coronary sinus oxygen content, suggesting a lack of activity at A2 adenosine receptors. CONCLUSIONS: An A1 adenosine receptor agonist exerts a marked protection against ischaemia induced ventricular arrhythmias and fibrillation in pigs. The reversal of this effect by restoring heart rate suggests that the drug induced bradycardia may be important in the antiarrhythmic action of R-PIA, possibly via an anti-ischaemic effect. PMID- 8458037 TI - Adenosine attenuates reperfusion injury following regional myocardial ischaemia. PMID- 8458038 TI - Metabolic and functional effects of the nucleoside transport inhibitor R75231 in the ischaemic and blood reperfused rabbit heart. AB - OBJECTIVE: The ability of R75231, a nucleoside transport inhibitor, to influence adenine nucleotide metabolism and enhance postischaemic functional recovery was assessed in the blood perfused rabbit heart. METHODS: Hearts (n = 8 per group) from donor animals were excised and perfused with blood at 37 degrees C from a support rabbit. After 20 min of aerobic perfusion hearts were arrested with St Thomas' Hospital cardioplegic solution (2 min at 37 degrees C) and rendered globally ischaemic for 60 min. This was followed by 60 min of reperfusion. R75231 (0.1 mg.kg-1, intravenously) was given to donor and support rabbits 1 h before the experiment, control rabbits receiving the same volume of vehicle. RESULTS: Treatment with R75231 resulted in a 45% reduction in coronary vascular resistance in aerobically perfused control hearts, an effect that was absent during postischaemic reperfusion. Thus, before ischaemia, coronary flow was greater in R75231 treated hearts [6.6(SEM 0.8) ml.min-1] than in controls [4.3(0.6) ml.min 1; p < 0.05] but during reperfusion no significant difference was observed [4.0(0.6) v 3.6(0.3) ml.min-1]. The mean time to onset and extent of contracture during ischaemia was similar in R75231 treated and control groups, at 42(4) v 41(4) min and 27(3) v 26(6) mm Hg, respectively. Left ventricular developed pressure recovered to approximately 50% of its preischaemic value during the first 40 min of reperfusion in both groups; however, after longer durations of reperfusion, it tended to deteriorate in the R75231 treated group whereas it was maintained at a constant level in the controls [37(10) v 53(6) mm Hg, respectively; NS]. At the end of reperfusion, tissue adenosine content was 13 fold greater in the R75231 treated group, at 0.40(0.09) v 0.03(0.01) mumol.g-1 dry wt in controls; p < 0.05; the nucleotide pool, nicotinamide adenine dinucleotide phosphate content, and the energy charge potential were similar in groups. CONCLUSIONS: R75231 decreased coronary vascular resistance and increased coronary flow during aerobic perfusion in control hearts, an effect that was lost after ischaemia and reperfusion. R75231 also increased greatly the tissue content of adenosine but, despite this, failed to improve either the recovery of cardiac contractile function or the replenishment of the adenine nucleotide pool. PMID- 8458039 TI - Adenosine increases lactate release and delays onset of contracture during global low flow ischaemia. AB - OBJECTIVE: Adenosine reduces myocardial ischaemic injury and enhances postischaemic recovery of function following zero flow global and regional ischaemia. The purpose of this study was to determine the functional and metabolic effects of endogenous and exogenous adenosine during low flow ischaemia. METHODS: Isolated perfused rat hearts (n = 80), paced at 300 beats-min 1, were subjected to 45 min of low flow ischaemia (0.6 ml.min-1). The time to onset of ischaemic contracture (TOIC) was used as a marker of myocardial ischaemic injury. Coronary venous effluent samples were collected prior to and throughout ischaemia to measure lactate and purine release. Untreated hearts were compared to hearts treated with either adenosine (100 microM), adenosine plus EHNA (erythro-9-[2-hydroxy-3-nonyl]adenine HCl), an adenosine deaminase inhibitor (50 microM), or BW A1433U, an adenosine receptor blocker (5 microM). RESULTS: Adenosine and adenosine+EHNA prolonged TOIC from 11.6 (SEM 0.5) min to 13.6(0.5) and 13.5(0.3) min, respectively, and increased lactate release from 1.67(0.19) mumol.min-1.g-1 to 2.20(0.09) and 2.35(0.31) mumol.min-1.g-1, respectively, after 20 min ischaemia. Treatment with BW A1433U reduced TOIC [8.7(0.2)min] and markedly reduced lactate release. When glucose was omitted from the perfusate, adenosine+EHNA treatment had no effect on TOIC. Lactate release during glucose free perfusion was similar to that in hearts treated with the adenosine receptor blocker. CONCLUSIONS: Endogenous and exogenous adenosine may enhance myocardial tolerance to ischaemia in part via the modulation of glucose metabolism. PMID- 8458040 TI - In vitro activity of clarithromycin, cefprozil, and other common oral antimicrobial agents against gram-positive and gram-negative pathogens. AB - Macrolide and beta-lactam antimicrobial agents are frequently used for the treatment of upper and lower respiratory tract infections and skin or skin structure infections. To evaluate the relative in vitro activity of these antimicrobial drugs against organisms commonly involved in these infections, we tested clarithromycin, erythromycin, cefprozil, cefuroxime, cefaclor, cephalexin, amoxicillin, amoxicillin/clavulanate, and doxycycline against 174 gram-positive and gram-negative clinical isolates, including Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, group A beta-hemolytic streptococci, alpha-hemolytic streptococci, Escherichia coli, and Klebsiella pneumoniae. Manual broth microdilution susceptibility testing was used with a standard inoculum of 5 x 10(4) colony-forming units/well at pH of 7.2. Clarithromycin was the most active agent against streptococci. Methicillin susceptible S aureus exhibited resistance to both clarithromycin and erythromycin, but was susceptible to cefprozil, cefuroxime, amoxicillin/clavulanate, and doxycycline. Cefprozil was at least as active as cefuroxime, cefaclor, and cephalexin against all organisms tested, but was fourfold less active than doxycycline against E coli and 16-fold less active than clarithromycin versus S pneumoniae. The gram-negative isolates tested showed resistance to clarithromycin and erythromycin; however, cefprozil was as active as amoxicillin/clavulanate against K pneumoniae and E coli. These results demonstrate that clarithromycin provides superior in vitro activity against common streptococci, while cefprozil, cefuroxime, amoxicillin/clavulanate, and doxycycline provide greater activity against methicillin-susceptible S aureus, K pneumoniae, and E coli. Prospective clinical trials are needed to determine the clinical significance of these findings. PMID- 8458041 TI - Antidepressant efficacy and cardiac safety of trimipramine in patients with mild heart disease. AB - The antidepressant efficacy and cardiac safety of trimipramine were evaluated in 22 depressed patients with mild heart disease (New York Heart Association class I, II, or III) who received doses of 50 to 200 mg/day for 28 days. Efficacy was evidenced by a significant decrease from baseline in Hamilton Rating Scale for Depression scores. The only significant change from baseline in electrocardiographic, Holter monitor, myocardial function, or vital sign evaluations was a transient prolongation of the mean QRS interval. None of the adverse reactions involved the cardiovascular system. The results demonstrate that trimipramine is effective in the treatment of depression and is not likely to produce serious or harmful cardiovascular side effects in patients with mild heart disease. PMID- 8458042 TI - Multicenter, double-blind, controlled comparison of zolpidem and triazolam in elderly patients with insomnia. AB - The efficacy and safety of zolpidem, a hypnotic of a new chemical class (the imidazopyridines), was compared with a reference benzodiazepine in elderly insomniac patients in a randomized, double-blind, multicenter trial. Hospitalized patients aged 58 to 98 years were randomized to receive zolpidem 5 mg (70 patients), zolpidem 10 mg (74 patients), or triazolam 0.25 mg (77 patients) at bed-time. (Three patients were excluded and 13 patients did not complete the study.) The 3-week active treatment period was preceded by 3 and followed by 7 days of placebo administration. Sleep quality was assessed by the patient via a questionnaire and visual analog scale. A clinician's global impression was also recorded. All measures of sleep quality were improved by both doses of zolpidem and by triazolam. The improvements between the end of the placebo phase and the end of the active treatment phase were significant for all treatments and assessment instruments. Moreover, the significant improvements in all measures were maintained during the week following withdrawal of both doses of zolpidem. The improvement in most sleep assessment parameters was maintained after withdrawal of triazolam. Tolerability of all treatments was excellent. The majority of patients reported no adverse effects. The reported adverse effects in all groups included nightmares, daytime drowsiness, and day- or nighttime agitation. There was no evidence of rebound insomnia; the therapeutic effect of zolpidem outlasted drug treatment. There were no signs of agitation or anxiety following cessation of treatment, which might be indicative of withdrawal phenomena. Confusion was recorded only in the triazolam group. These results suggest that zolpidem is at least as effective as triazolam in geriatric insomniac patients. Zolpidem 5 mg and 10 mg demonstrated a good safety profile. On the basis of these data, zolpidem 5 mg should be given as a starting dose in elderly patients, with a possible increase up to 10 mg in more severe cases of insomnia. PMID- 8458043 TI - Antitumor and endocrine effects of an aromatase inhibitor (CGS 16949A) on DMBA induced rat mammary tumor. AB - The antitumor and endocrine effects of a new nonsteroidal aromatase inhibitor were studied using DMBA-induced rat mammary carcinomas. CGS 16949A (CGS) was administered orally once daily for 3 weeks. A marked antitumor effect was noted at doses of more than 1 mg/kg, and weight gain was dose dependent. Histologic examination showed atrophic changes of the tumors and decreased expression of estrogen receptor levels. To investigate the mechanism of the antitumor effect of CGS, we studied the changes in endocrine function in rats given this agent. In the groups receiving more than 1 mg/kg of CGS, the serum estradiol and prolactin levels were lower and the serum luteinizing hormone level was higher than in the control group. In rats treated with CGS, ovary weight was increased, while uterus and pituitary weights were decreased. These changes were dose dependent. In contrast, the serum corticosterone level and adrenal weight remained unchanged. We conclude that CGS inhibits the growth of hormone-dependent tumors by changing the hormonal environment. PMID- 8458044 TI - Double-blind comparison of etodolac and piroxicam in the treatment of rheumatoid arthritis. AB - Etodolac is the first of a new class of nonsteroidal anti-inflammatory drugs--the pyranocarboxylic acids--and has potent analgesic and anti-inflammatory properties. Etodolac and piroxicam were compared in the treatment of patients with active rheumatoid arthritis. A total of 118 patients entered this double blind parallel study and were randomly assigned to receive 200 mg of etodolac twice a day (60 patients) or 20 mg of piroxicam once a day (58 patients) for 12 weeks. After the baseline evaluation, efficacy and tolerability evaluations were made at 2, 4, 6, 8, and 12 weeks. Significant improvement from baseline was noted in both treatment groups in the patient's and physician's global evaluations, in the number of swollen and tender joints, and in the pain intensity scores. Improvement was noted at the first visit (week 2) and continued through week 12. Based on changes in the patient's global evaluation, 56% of the etodolac-treated patients and 47% of the piroxicam-treated patients showed improvement at the final evaluation. Based on changes in the physician's global evaluation, 47% of the etodolac-treated patients and 42% of the piroxicam-treated patients showed improvement at the final evaluation. Eight (13%) patients in the etodolac group and 7 (12%) patients in the piroxicam group withdrew from the study because of adverse events. Most adverse events were mild to moderate; gastrointestinal complaints were the most prevalent adverse events in both treatment groups. No clinically significant changes were seen in laboratory test results or vital signs. These results demonstrate that etodolac is well tolerated and effective in the treatment of the signs and symptoms of rheumatoid arthritis and compares favorably to piroxicam in safety and efficacy. PMID- 8458045 TI - Efficacy of transnasal butorphanol tartrate in postepisiotomy pain: a model to assess analgesia. AB - Butorphanol tartrate, a synthetically derived opioid agonist-antagonist analgesic, was tested in a large group of postpartum women (N = 76) to assess the safety and analgesic efficacy of a recently approved transnasal preparation of this drug in the relief of postepisiotomy pain. The safety and efficacy of intravenous and intramuscular administration of butorphanol tartrate has been established over 14 years of clinical use. The new nasal spray dosage form offers a similar degree of efficacy with a rapid onset of action. Compared with the injectables and other drugs in this class, transnasal butorphanol has a longer duration of action (4 to 5 hours). In this double-blind, parallel-group, dose response study, 76 female patients ages 17 to 37 years with moderate to severe postepisiotomy pain were randomly assigned to receive a single dose of transnasal butorphanol (0.25, 0.5, 1, or 2 mg) or placebo. The patients were evaluated for 6 hours. The results of the study indicate that the 1-mg and 2-mg doses were associated with greater efficacy compared with placebo using several markers for efficacy, including the pain relief score and time to remedication. The drug was well tolerated, dizziness and drowsiness being the most frequently reported adverse effects. Adverse effects appeared to be dose related. PMID- 8458046 TI - Safety, efficacy, and cost savings in an outpatient intravenous antibiotic program. AB - We analyzed the costs of an outpatient intravenous (IV) treatment program using a broad-spectrum, third-generation cephalosporin. Fifty-six patients were treated for various infections in a hospital-based outpatient IV antibiotic program. The mean length of outpatient treatment was 7.4 days (range, 2 to 24 days). Infections in 53 patients resolved successfully, with only 3 patients experiencing recurrence. Side effect were minimal, with no significant toxicities; one case of oral candidiasis and one case of rash occurred. Collectively, the 56 patients were treated for 286 days in the hospital and 414 days in an outpatient program. Costs were totaled on a weekly basis and divided by seven to arrive at a daily charge; the antibiotic most frequently prescribed was used as the representative regimen. The mean cost for each hospital day was $417 compared with $155 per outpatient day, a savings of $262 on a daily basis. We conclude that outpatient IV antibiotic therapy is safe and effective for a variety of infections in a wide range of patients and can contribute to substantial financial savings. PMID- 8458047 TI - Pharmacoeconomic issues in the use of granulocyte-macrophage colony-stimulating factor for bone marrow transplantation or chemotherapy-induced neutropenia. AB - As new treatment options become available for patients with cancer or primary bone marrow failure, the additional economic burden that these treatments may place on the already stressed health care system raises concerns. Neutropenia is a major complication of these conditions and can add substantially to patient care costs. Granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine that enhances neutrophil production and function, has recently been recommended as an effective treatment for neutropenia. Selected clinical studies suggest that GM-CSF can reduce the costs associated with the management of neutropenic patients by reducing the need for antibiotics and the duration of hospitalization. Treatment with GM-CSF also may be associated with an improved quality of life. Pharmacoeconomic and quality-of-life studies are required, however, to document these benefits. Based on currently available data, GM-CSF represents an economically and clinically appropriate treatment approach for neutropenia in patients who have undergone bone marrow transplantation or experience chemotherapy-induced neutropenia. PMID- 8458048 TI - Clinical properties of yeast-derived versus Escherichia coli-derived granulocyte macrophage colony-stimulating factor. AB - Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) can be expressed in yeast, bacteria, or mammalian cells. Expression in each system results in a protein that differs, to a varying extent, from native GM-CSF. Like the native protein, yeast-expressed GM-CSF is glycosylated and has 127 amino acids, but differs from native GM-CSF in molecular mass and in the substitution of leucine for proline at position 23. GM-CSF expressed in Escherichia coli bacteria is not glycosylated, has six fewer amino acids than the native protein, and an extra methionine at position 1. A review of laboratory studies shows that these differences in physiochemical properties result in variations in the pharmacokinetics, biologic activity, and immunogenicity of GM-CSF expressed in different host cells. These variations may lead to an increased clinical toxicity with GM-CSF expressed in E coli versus that produced in yeast. A total of 32 clinical trials were reviewed to determine the relative frequency of adverse events in patients treated with GM-CSF expressed in E coli versus that expressed in yeast. In general, the median reported frequency of adverse events was higher in patients treated with E coli-derived GM-CSF. The median frequencies of fluid retention, dyspnea, fever, myalgias/bone pain/joint pain, and rash were 8.3%, 13.4%, 21.7%, 16%, and 14.3%, respectively, in patients receiving GM-CSF expressed in yeast, versus 18.4%, 55.2%, 40.7%, 28.5%, and 12.5%, respectively, in patients treated with GM-CSF expressed in E coli. Thus data in the literature support the view that the GM-CSF expression system influences the pharmacokinetic properties, biologic activity, and clinical toxicity of GM-CSF. PMID- 8458049 TI - Anemia in women ages 20 to 89 years: rationale and tools for differential diagnosis. AB - Anemia is an underdiagnosed condition warranting intensified screening efforts. By conducting more systematic laboratory testing and by obtaining more interpretive test reports, physicians can greatly improve their recognition, diagnosis, and management of anemic patients. One way to improve the diagnosis and ultimate treatment of anemia is to categorize the condition using two parameters in the blood count--red blood cell size, measured as mean corpuscular volume (MCV), and variability of red blood cell size (anisocytosis), determined by red cell volume distribution width (RDW). Our study of anemic women aged 20 to 89 years examined the two parameters of RDW and MCV. Based on the anemia classification scheme devised by J.D. Bessman et al, the red cells of all of the patients studied were categorized as follows: heterogeneous microcytic (HTMI), homogeneous microcytic (HMMI), heterogeneous normocytic (HTN), homogeneous normocytic (HMN), heterogeneous macrocytic (HTMA), or homogeneous macrocytic (HMMA). HMN anemia, often linked with the anemia of chronic disease, was the most common type in all age groups, representing 60% to 76% of all cases of anemia. HTMI anemia occurred most frequently in women between the ages of 30 and 49 years, an expected finding. The HTN and HMMA anemias occurred somewhat more frequently in older patients. Through an initial classification of anemia based on MCV and RDW, the clinician has the groundwork for further testing that will lead to a diagnosis. PMID- 8458050 TI - Conscientious objection and abortifacient drugs. AB - The legal right to assert a conscientious objection is reviewed, using as an example the dispensing of abortifacient drugs by pharmacists. The three areas of law that most significantly concern the right to assert a conscientious refusal are employment law, conscience clauses, and religious discrimination law. Each of these is reviewed, with descriptions of recent cases. It is concluded that employment law protects refusals that are consistent with public policy, but does not permit an employee's personal policy to determine how a business will be run; that conscience clauses appear to provide protection for pharmacists who object to dispensing abortifacients, but that the precise meanings of critical words and phrases in some clauses need to be defined; and that even though laws of religious discrimination require that employers accommodate religious beliefs, they may not protect a pharmacist who objects to dispensing abortifacients if the accommodation becomes unreasonably burdensome. PMID- 8458051 TI - Renal effects of angiotensin converting enzyme inhibitors in heart failure: a clinician's guide to minimizing azotemia and diuretic-induced electrolyte imbalances. AB - Angiotensin converting enzyme (ACE) inhibitors have proved to be valuable, life saving medications in the management of heart failure. While reducing myocardial oxygen consumption, they increase cardiac output and thus renal plasma flow. Despite reports in the literature of adverse effects of these drugs on renal function, the risks of functional deterioration are predictable in patient populations and remediable. Patients at greatest risk of declining renal function during therapy with ACE inhibitors are those in whom maintenance of renal function is dependent on angiotensin II. Reducing the dose of the concomitant diuretic, liberalizing the dietary intake of sodium, and increasing the dose of the ACE inhibitor usually restores renal function to baseline. In patients with severe renal insufficiency, reducing the dose of the ACE inhibitor might be necessary to preserve the glomerular filtration rate. PMID- 8458052 TI - Protein removal from soft contact lens using disinfection/neutralization with hydrogen peroxide/catalytic disc. AB - The purpose of this study was to determine whether protein deposits on soft contact lens could be removed without digital or enzymatic cleaning. Group IV soft contact lenses were incubated in an artificial tear solution of lysozyme, albumin, mucin, calcium chloride, and sodium phosphate. The amount of protein on the lenses was determined using a total protein assay with ninhydrin derivation. Mean (+/- SD) protein levels were significantly higher on untreated lenses (598 +/- 184 micrograms) than on lenses treated with hydrogen peroxide and a catalytic disc (360 +/- 51 micrograms). These findings are discussed in light of the finding that one third of contact lens wearers do not digitally clean their lenses after each use and one half do not use an enzymatic cleaner at least once a week. It is concluded that hydrogen peroxide/catalytic disc-based soft contact lens disinfection can remove up to 40% of the protein deposited on soft contact lenses. PMID- 8458053 TI - Efficacy of famotidine in the healing of active benign gastric ulceration: comparison of nonsteroidal anti-inflammatory- or aspirin-induced gastric ulcer and idiopathic gastric ulceration. Long Island Jewish Medical Center Acid-Peptic Study Group. AB - Seventy-one of 85 consecutive patients with endoscopically confirmed active benign gastric ulcers completed an 8-week study to evaluate the effects on healing of famotidine 40 mg given as a single dose at night. The healing rate in the 48 patients in whom the ulcers were associated with nonsteroidal anti inflammatory drug (NSAID) or aspirin (ASA) use was compared with that in the 23 patients with idiopathic ulcers. Endoscopy, symptom assessments, antacid use, hematology, and serum chemistry were performed at weeks 4 and 8 of treatment. Famotidine 40 mg at bedtime healed 63 (89%) of the 71 ulcers at 8 weeks; the healing rate for NSAID/ASA-associated ulcers was 46 (96%) of 48, which was significantly greater than that for idiopathic ulcers (17 of 23; 74%) (P = 0.0119). Of the 54 patients who returned a questionnaire 1 to 2 years after completing the study, 20% were still taking an NSAID/ASA (mainly for cardiovascular prophylaxis). About half of the patients surveyed were taking anti ulcer medication. None of these patients had experienced any serious ulcer complication. The results of this study suggest that differentiating NSAID/ASA induced ulcers from idiopathic ulcers may be important with regard to healing rates and duration of therapy. PMID- 8458054 TI - Comparative evaluation of cefadroxil and cephalexin in children and adolescents with pyodermas. Cefadroxil Once Daily Pyoderma Study Group. AB - This randomized, multicenter study compared the safety and efficacy of cefadroxil with that of cephalexin for the treatment of pyodermas in children and adolescents (1-18 years of age). Cefadroxil was given as a single oral daily dose of 30 mg/kg, and cephalexin 30 mg/kg/day was given in two divided doses. The maximum daily dose for both drugs was 1 gm, and treatment was administered for 10 days. Clinical and bacteriologic evaluations were made on days 4 or 5 during therapy and 2 to 4 days after therapy was completed. Of the 462 patients enrolled in the study, 156 patients in the cefadroxil group and 133 patients in the cephalexin group were evaluable. Staphylococcus aureus (56% of isolates) and Streptococcus pyogenes (39% of isolates) were isolated most frequently. The bacteriologic response was statistically greater in the patients treated with cefadroxil than in those treated with cephalexin (96% versus 89%; P = 0.042). A satisfactory clinical response was reported in 147 (94%) cefadroxil-treated patients and 122 (92%) cephalexin-treated patients (P = 0.476). The overall effective response to treatment was significantly higher with cefadroxil than with cephalexin (94% versus 86%; P = 0.024). Compliance with 9 or 10 days of therapy was similar in both treatment groups, although there was a difference between the two treatment groups with respect to completion of medication regimen: 95% of patients taking cefadroxil once daily--versus 65% of patients taking cephalexin twice daily--took 100% of their medication (P < 0.0001). Adverse events were infrequent and mild. The results of this study demonstrate that once-daily cefadroxil offers greater bacteriologic eradication and a better overall effective response than twice-daily cephalexin for the treatment of pyodermas caused by gram-positive pathogens in children and adolescents. PMID- 8458055 TI - Long-term experience with pravastatin in clinical research trials. AB - Pravastatin is a new lipid-lowering drug belonging to the class of 3-hydroxy-3 methylglutaryl CoA (HMG-CoA) reductase inhibitors. Since 1986, more than 15,000 patients have received pravastatin in sponsored clinical research trials with more than 21,000 cumulative patient-years of exposure to the drug. Analysis of long-term follow-up data from 1142 patients participating between 1986 and 1990 in six core randomized clinical trials in the United States confirms the favorable safety profile of pravastatin. Rash, gastrointestinal complaints, musculoskeletal pain, and elevations in liver transaminase levels, whether or not attributed to treatment, were the most common reasons for patients withdrawing from these trials. Ophthalmologic monitoring revealed no adverse effects on the crystalline lens. Safety assessments continue for two core trials in more than 400 patients with up to 7 years of continuous follow-up. The effects of pravastatin on serum cholesterol levels are not influenced by the age, sex, weight, or initial cholesterol level of the patient. Vitamin E, A, and D metabolism remain normal during treatment. Combination therapy with pravastatin and bile-acid-binding resins or niacin is well tolerated, with additive effects on low-density lipoprotein cholesterol. There is limited experience with the combination of pravastatin and gemfibrozil or cyclosporine. An ongoing arteriosclerosis research program with more than 21,000 patients enrolled will further define the long-term safety of pravastatin and its effects on atherosclerosis progression, as well as its role in the primary and secondary prevention of coronary heart disease. PMID- 8458056 TI - Comparison of empiric aztreonam and aminoglycoside regimens in the treatment of serious gram-negative lower respiratory infections. AB - An open-label, controlled, randomized study was performed to assess the efficacy and safety of combination regimens using either aztreonam or an aminoglycoside control regimen as empiric therapy for suspected aerobic gram-negative bacillary pneumonia or purulent bronchitis. Eighty-four patients, 42 in each arm of the study, were randomly assigned to one of two treatment regimens. The combination aztreonam regimen included aztreonam, 2 gm every 8 hours (q8h), plus either clindamycin, 600 to 900 mg q8h, or nafcillin, 1.5 gm to 2 gm every 6 hours (q6h). The control regimen was one of the following depending on the combination therapy that was designated standard at each of the three study institutions: amikacin, 5 mg/kg q8h, plus cefazolin, 1 gm q8h; amikacin, 500 mg every 12 hours plus mezlocillin, 4 gm q6h; or kinetically dosed tobramycin plus ticarcillin, 3 gm to 4 gm q4h. The two groups were well matched in terms of demographics and clinical characteristics. Among the 84 patients, organisms from the Enterobacteriaceae family accounted for the largest proportion of isolates (44%) including Escherichia coli (13%), Klebsiella species (14%), and Serratia species (9%). Other commonly identified organisms were Pseudomonas aeruginosa (19%), Haemophilus influenzae (15%), Streptococcus pneumoniae (12%), and Staphylococcus aureus (8%). Results of this trial included clinical response rates of 83% in both groups (P = 0.951) and a microbiologic cure rate of 75% in the aztreonam group and 63% in the control group (P = 0.291). In the 59 patients with documented aerobic gram-negative pneumonia, microbiologic eradication rates were 72% in the aztreonam group versus 57% in the control group (P = 0.359). Duration of treatment tended to be shorter in the aztreonam group than in the control group, with a median 10 days of therapy versus 12 days of therapy (P = 0.095), respectively. In addition, the percentage of patients requiring nonstudy antimicrobial agents tended to be lower in the aztreonam group than the control group, involving 21% of patients in the aztreonam group compared with 36% of patients in the control group (P = 0.086). All regimens were well tolerated, and no patient was withdrawn because of adverse reactions to the study medications. Two patients, both in the control group, required dose reduction, which was necessitated by possible aminoglycoside-induced nephrotoxicity. This trial shows that aztreonam is an effective agent with an excellent safety profile when used in combination regimens for the empiric treatment of pneumonia. A well-controlled trial is needed to verify the trend toward shorter hospital stays and a reduced need for additional antimicrobial agents seen with the aztreonam regimen when compared with those receiving aminoglycoside-combination regimens. PMID- 8458057 TI - Double-blind, placebo-controlled study of ramipril in diabetics with mild to moderate hypertension. AB - Although hypertension and diabetes mellitus frequently appear as comorbidities, the pharmacotherapy of hypertension in patients with diabetes mellitus can aggravate underlying carbohydrate and lipid abnormalities. To evaluate the efficacy and safety of the long-acting angiotensin converting enzyme inhibitor ramipril in patients with insulin-dependent or non-insulin-dependent diabetes mellitus, the authors conducted a double-blind, placebo-controlled study. After a single-blind washout period, 58 patients were randomly assigned to receive 2.5 mg of ramipril or a 2.5-mg placebo, each once daily. Each patient underwent titration and maintenance phases for a total treatment period of 12 weeks. By the end of maintenance, 54% of patients maintained the target blood pressure 24 hours after receiving ramipril compared with 19% in the placebo group (P = 0.008). Between baseline and the end of maintenance, ramipril decreased mean supine systolic/diastolic blood pressure (SBP/DBP) measured 24 hours after the last dose by 9/8 mmHg (P < or = 0.001/P < or = 0.001); placebo decreased SBP/DBP by 2/4 mmHg (NS/P < or = 0.05). Between-group differences were significant (P < 0.05). During this time, blood glucose, hemoglobin Alc, lipoproteins, and biochemistry were unchanged in the ramipril group. There were no between-group differences in the number or types of adverse events. In our study of patients with diabetes mellitus, once-daily ramipril controlled blood pressure, was well tolerated, and had no effects on carbohydrate or lipid metabolism. PMID- 8458058 TI - Global surveillance of bacterial susceptibility to cefaclor: 1988-1990. AB - In vitro data on bacterial susceptibility to cefaclor were collected from clinical trials conducted in 15 European countries, South Africa, Canada, and the United States. Among the respiratory pathogens, 94% of Haemophilus influenzae, 98.6% of Streptococcus pneumoniae, 98.8% of Streptococcus pyogenes, and 98.1% of Moraxella catarrhalis were susceptible to cefaclor. Over 90% of the tested isolates of the most common urinary tract pathogen, Escherichia coli, were susceptible to cefaclor. Virtually all of the pathogens that may infect skin and soft tissues, S pyogenes and Staphylococcus aureus (methicillin-susceptible strains), were cefaclor susceptible. These data confirm that the major pathogens in bacterial infections of the upper and lower respiratory tract, of the skin and related structures, and of the urinary tract remain susceptible to cefaclor after more than 13 years of widespread clinical use. PMID- 8458059 TI - Acid-suppression profile of two continuously infused intravenous doses of cimetidine. AB - The effect of two doses (37.5 mg/hr and 50 mg/hr) of continuously infused cimetidine on gastric acid secretion and pH control over 24 hours was compared with that of placebo in 21 adult males with active duodenal ulcer or scarring from healed duodenal ulcer. This single-center, double-blind, three-way crossover trial consisted of three treatment periods separated by 5- to 7-day washout periods. Gastric contents were continuously aspirated through a nasogastric tube during the second half of each study hour. Volume, pH, and titratable acidity were measured from the aspirates collected during the last 20 minutes of each aspiration period. The median pH, volume (ml), and titratable acidity (mEq/hr) values for the 37.5-mg/hr infusion were 5, 16.0, and 0.24, respectively (P < 0.05 versus placebo). For the 50-mg/hr infusion, the respective values were 5.3, 15.8, and 0.14 (P < 0.05 versus placebo); and for placebo, the values were 1.4, 30.5, and 6.83. The median percent of time that the pH was > or = 4 was 65%, 65%, and 0% for the 37.5-mg/hr, 50-mg/hr, and placebo infusions, respectively (P < 0.05 versus placebo). The 37.5-mg/hr and 50-mg/hr intravenous doses of continuously infused cimetidine are commonly used in the hospital setting to treat intractable ulcers or prevent upper gastrointestinal bleeding in critically ill patients. The results of this study demonstrate that both doses are similarly effective in maintaining intragastric pH and acid secretion at levels generally recognized as being effective. PMID- 8458060 TI - Increased production of endothelins in the hippocampus of stroke-prone spontaneously hypertensive rats following transient forebrain ischemia: histochemical evidence. AB - 1. The effect of transient forebrain ischemia on endothelin-1 (ET-1) and endothelin-3 (ET-3) production in the hippocampus of stroke-prone spontaneously hypertensive rats (SHRSPs) was investigated using immunohistochemical techniques. 2. In SHRSPs subjected to 10-min bilateral carotid occlusion, neuronal degeneration in the CA1 pyramidal cell layer of the hippocampus was detectable at 4 days and remarkable at 7 days after reperfusion. 3. Coinciding with neuronal degeneration, ET-1- and ET-3-like immunoreactivities were intense in the CA1 pyramidal-cell layer, the stratum lacunosum moleculare, and the CA4 subfield of the hippocampus. Almost all of the immunostained cells had morphological characteristics of astrocytes. 4. The possibility that ET has a role in the development of neuronal cell death following transient forebrain ischemia warrants further attention. PMID- 8458061 TI - Expression and reconstitution of biologically active human acetylcholinesterase from Escherichia coli. AB - 1. Authentic human acetylcholinesterase (AChE) was expressed in Escherichia coli under regulation of the constitutive deo promoter or the thermo-inducible lambda PL promoter. 2. To facilitate expression in the prokaryotic system, recombinant human AChE (rhAChE) cDNA was modified at the N terminus by oligonucleotide substitutions in order to replace some of the GC-rich regions by AT. These modifications did not alter the amino acid sequence but resulted in ample production of the protein. 3. rhAChE accumulated in the cells and reached a level of 10% of total bacterial proteins. A partially purified inactive recombinant protein was recovered from inclusion bodies. 4. Active rhAChE was obtained after solubilization, folding, and oxidation, although the recovery of the active enzyme was low. A 20- to 40-fold increase in enzymatically active rhAChE was achieved by replacing Cys580 by serine. 5. The recombinant enzyme analogue was indistinguishable from native AChE isolated from erythrocytes in terms of substrate specificity and inhibitor selectivity. PMID- 8458062 TI - A 28-kDa cerebral neuropeptide from Manduca sexta: relationship to the insect prothoracicotropic hormone. AB - 1. A 28-kDa peptide from the brain of the tobacco hornworm, Manduca sexta, was purified via HPLC. The peptide copurified with the insect neurohormone, prothoracicotropic hormone (PTTH), through two HPLC columns. 2. Immunocytochemistry using polyclonal antibodies against the 28-kDa peptide revealed that the peptide was produced in the same protocerebral neurons that produce PTTH. Western blot analysis demonstrated that the 28-kDa peptide and big PTTH are different molecules. 3. A PTTH in vitro bioassay indicated that despite having chromatographic properties similar to those of big PTTH and being produced by the same neurons, the 28-kDa peptide did not have PTTH activity. 4. Amino acid sequence analysis yielded a 27 N-terminal amino acid sequence that had no similarity with known peptides. 5. Immunocytochemical studies revealed that the 28-kDa peptide is present as early as 30% embryonic development and is absent by adult eclosion. This is in contrast to big PTTH, which is expressed throughout the Manduca life cycle. 6. These data suggest that the 28-kDa peptide is another secretory phenotype of the lateral neurosecretory cell group III (L-NSC III) which may have functions distinct from those for big PTTH or may act synergistically with big PTTH. PMID- 8458063 TI - Dendrotoxin blocks a class of potassium channels that are opened by inhibitory presynaptic modulators in rat cortical synaptosomes and slices. AB - 1. Rat cortical synaptosomes were prelabeled with radioactive acetylcholine and the release induced by veratridine was determined in the absence and presence of the inhibitory presynaptic modulators, 2-chloroadenosine, carbamylcholine, clonidine, and morphine. All four agents inhibited the evoked release of acetylcholine and this inhibition was reversed by dendrotoxin. 2. Using perfused cortical slices and an extracellular K-sensitive electrode, all modulators again increased K efflux that was blocked by dendrotoxin. In contrast, glybenclamide and tetraethylammonium did not block the modulator-induced efflux. PMID- 8458065 TI - [The effect of weather and climate on the healthy and ill individual]. AB - It has been known for thousands of years that changes of the weather and climate influence in a significant way man in health but in particular in disease. In the submitted paper the author describes different mechanisms of action of the mentioned factors, risk situations and also possible ways how to prevent adverse influences or to reduce at least their effect. In the conclusion the author mentions problems of biometeorological forecasts and the importance to take into account also extra-terrestrial influences. It is remarkable that less attention is paid to detailed, in particular experimental research, than corresponds to the serious character of disorders and their impact on the health status of the population. PMID- 8458064 TI - Regulation of vasopressin gene expression: changes in the level, but not the size, of vasopressin mRNA following endocrine manipulations. AB - 1. Regulatory interactions between the hypothalamoneurohypophyseal vasopressin (VP) axis and the endocrine systems of the anterior pituitary have been investigated in the rat by observing changes in VP mRNA expression following endocrine manipulations. 2. An increase in the level, but not size, of VP mRNA was found in the supraoptic (SON) and paraventricular nuclei (PVN) of the hypothalamus and in the neurointermediate lobe (NIL) of the pituitary following hypothyroidism (induced by drinking 6-n-propyl-2-thiouracil; PTU) and adrenalectomy. Hypothyroidism induced by alternative procedures (surgical thyroidectomy or PTU injections) did not exert similar effects. 3. Treatment with the dopamine agonist bromocriptine to reduce prolactin secretion raised levels of VP mRNA in the NIL only. Castration did not up-regulate VP mRNA levels. 4. Since the observed effects on VP mRNA levels occur in the absence of changes in plasma osmolality, these results provide evidence of nonosmotic regulation of VP gene expression, an effect which is observed most clearly in the NIL pool of VP mRNA. Furthermore, the effects are distinct from changes in VP mRNA levels associated with raised plasma osmolality since the VP mRNA size was not increased. PMID- 8458066 TI - [Idiopathic hypercalciuria--the effect of physical stress on calciuria]. AB - The authors investigated calciuria (dU-Ca) in a group of 37 patients with confirmed idiopathic hypercalciuria. The group comprised 17 men, mean age 46.1 +/ 10.4 years, and 20 women, mean age 55.7 +/- 14.9 years (on statistical evaluation the group of women was significantly older, p > 0.01). After a load the calciuria declined in men by 27.3%, in women by 31.3%, in the total group by 27.85% (all reduced values are statistically significant as compared with controls, p < 0.001). In individual subjects calciuria declined by as much as 58%. Similar results were achieved during treatment with hydrochlorothiazide: the drop of calciuria during a physical load in men was 27.60%, in women 34.70%. The group of patients who participated in the whole programme, i.e. rest/load and rest/load after one month hydrochlorothiazide treatment, 25 mg/day, is too small for conclusive evaluation. CONCLUSION: physical load and hydrochlorothiazide reduce the amount of calcium excreted in urine by patients with idiopathic hypercalciuria. PMID- 8458067 TI - [The Prague Diabetes Registry--computer utilization. 2. Body mass index, family history, manifestation of diabetes mellitus]. AB - Eighty percent of all diabetic patients in Prague, incl. those with IGT, are overweight. There are 4.6 times as many obese female diabetics, as compared with normal weight type 2 diabetics. Among type 2 male diabetics there are 1.9 times more obese ones. A familial incidence of diabetes is reported by 42% type 1 diabetics and 36% type 2 diabetics. In 64.7% of type 2 diabetics diabetes was detected accidentally. In the group of type 1 diabetics in 92.1% diabetes was detected from clinical manifestations incl. coma. PMID- 8458068 TI - [Measurement of impedance in liver tissue]. AB - At the First Medical Clinic (First Medical Faculty, Charles University) a new method of assessment of impedance of hepatic tissue was developed. A special thin injection electrode was designed which makes it possible to take readings in deep tissue. The measurements are made and aimed throughout the procedure under ultrasonographic control. From the sites of assessment specimens were taken for cytological and histological examination. So far 44 operations were completed. In 33 patients according to ultrasonography focal changes were involved, in the remainder the liver parenchyma was homogeneous or there were slight diffuse changes. Based on the results of the histological examination, the group was divided into 11 subgroups some of which are very small and thus difficult to interpret. Therefore this is only a preliminary study. Its objective is to introduce the technique of a new method because even from the small hitherto assessed values of impedance by means of the injection electrode under ultrasonographic control the conclusion can be drawn that the assessed impedance values could provide more detailed information on the character of focal changes. PMID- 8458070 TI - [Hereditary pancreatitis]. AB - The authors describe a family with hereditary pancreatitis where in three generations in five subjects in the same line complete penetrance of the disease was found. It is the first report on this disease in Czech republic. PMID- 8458069 TI - [Parenteral, depot and repeatable forms of Parlodel LAR bromocriptine in the treatment of hyperprolactinemia syndrome. Comparison with oral Parlodel]. AB - Parenteral, depot, repeatable bromocriptine Parlodel LARR (PLO LAR) was used in the treatment of 10 women with hyperprolactinaemia. Two of them had previously an operation of a prolactinoma, eight did not have adenomas. Twenty eight days following administration of 50 mg PLO LAR, the PRL levels ere significantly lower than before treatment; in patients without adenomas they were quite normal. The action of the mentioned 50 mg PLO LAR corresponded roughly to a daily dose of 7.5 mg ParlodelR (PLO) by the oral route, i.e. in 28 days a total of 185 mg bromocriptine. After administration of five PLO LAR injections (50 and later 100 mg), the mean PRL levels in patients without adenomas were normal after 6 months. There were no significant nor pathological changes 28 days following i.m. PLO LAR 50 mg as regards T3, T4 levels, the blood sugar, cholesterol, FSH, LH, STH, TSH, testosterone cortisol, progesterone, 17 beta-estradiol, androstendione, 11 beta OH androstendione, DHEA-S, 17 alpha-OH progesterone, aldosterone, 17-ketosteroids and 17-ketogenic steroids (in urine). LHRH + TRH + insulin tolerance tests were made repeatedly. Significant changes were found only in PRL levels (decline). In three amenorrhoic patients the originally low progesterone level rose significantly to levels of postovulation progesterone. One of these three women became pregnant after 18 years of unsuccessful treatment of sterility, incl. various oral dopaminergic preparations. The patients tolerated the preparation well and various biochemical and haematological tests were normal. The effect on galactorrhoea was favourable, seven amenorrhoic women had normal menstruation. PMID- 8458072 TI - [Vietnamese medicine]. PMID- 8458071 TI - [Endoscopic ultrasonography of the upper part of the digestive tract. II]. AB - Endoscopic ultrasonography is a new method of visualization which makes it possible to visualize reliably and in detail the wall the digestive tract and its close surroundings. Indication is above all diagnosis of tumours and their staging. The authors submit their initial experience with the method in a group of 71 examinations in 65 subjects. The conclusions of endosonography were confirmed as correct in 96.7% and provide evidence of the asset and possibilities of the method in the differential diagnosis of diseases of the upper portion of the digestive tract. PMID- 8458073 TI - Current bibliography of cell calcium prepared by the University of Sheffield Biomedical Information Service. PMID- 8458074 TI - Calcium entry in Xenopus oocytes: effects of inositol trisphosphate, thapsigargin and DMSO. AB - Agonist- and inositol 1,4,5-trisphosphate (InsP3)-evoked responses in Xenopus oocytes utilize calcium mobilized from cellular stores as well as from the medium. We studied the effect of the status of Ca stores on InsP3-induced Ca entry. Thapsigargin (TG) caused a net increase of 45Ca2+ efflux from oocytes in a time and dose dependent manner (31 and 54% of total label, at 30 and 60 min, respectively). Incubation with TG (60 min) resulted in a complete loss of the response to InsP3 implying that InsP3-sensitive Ca stores were depleted. Challenge with 1.8 mM Ca2+ resulted in a large depolarizing chloride current (1231 +/- 101 nA) which was not further potentiated by InsP3. This suggested that extensive depletion of cellular Ca stores is sufficient to induce maximal entry of extracellular Ca (Cao). Following the injection of InsP3, a much more limited loss of cellular Ca was sufficient to produce large Ca entry. Dimethyl sulfoxide (DMSO) alone, the vehicle used to dissolve TG, did not cause increase in either efflux of 45Ca2+, nor in the Cao-evoked Cl- current. It did, however, markedly potentiate this current following the injection of InsP3. DMSO moderately inhibited InsP3-induced 45Ca2+ efflux from oocytes. Hence, apparent potentiation of Ca entry can be observed without additional depletion of cellular Ca. We conclude that Ca entry may be induced via either stimulation with InsP3 and limited Ca depletion or depletion of a specific and, possibly small, cellular Ca store alone. The mechanism of DMSO potentiation is unknown, but may be important in view of the universal use of this solvent as vehicle. PMID- 8458075 TI - The calcium concentration clamp: spikes and reversible pulses using the photolabile chelator DM-nitrophen. AB - New procedures are described for producing brief transients and reversible elevations in [Ca] that can be used to quantitatively control the concentration of cytoplasmic calcium. If the photolabile calcium chelator DM-nitrophen, partially bound to calcium, is exposed to steady illumination, [Ca] can be raised from a few nM to up to 10 microM for durations of 100 ms or longer, depending on light intensity and duration. An association rate of calcium with nitrophen of 1.5 x 10(6) M-1s-1 was estimated from measurements of [Ca] using the fluorescent indicator Fluo-3, and calcium was found to speed the photolysis of nitrophen 2.5 times. Partial photolysis of DM-nitrophen partly loaded with calcium elicits a [Ca] spike of over 100 microM lasting about 1 ms, depending on intensity and duration of the light flash. Simulations of the reactions involved predict changes in Fluo-3 fluorescence measured at high time resolution with a laser scanning confocal microscope. These procedures have been applied in physiological experiments to generate cytoplasmic [Ca] spikes and pulses and study the cellular responses to them. PMID- 8458076 TI - Planting alfalfa and cloning the Huntington's disease gene. PMID- 8458077 TI - Methanogenesis and the unity of biochemistry. PMID- 8458078 TI - Molecular mimicry and the generation of host defense protein diversity. PMID- 8458079 TI - Pigmentation phenotypes of variant extension locus alleles result from point mutations that alter MSH receptor function. AB - Coat colors in the chestnut horse, the yellow Labrador retriever, the red fox, and one type of yellow mouse are due to recessive alleles at the extension locus. Similarly, dominant alleles at this locus are often responsible for dark coat colors in mammals, such as the melanic form of the leopard, Panthera pardus. We show here that the murine extension locus encodes the melanocyte-stimulating hormone (MSH) receptor. In mice, the recessive yellow allele (e) results from a frameshift that produces a prematurely terminated, nonfunctioning receptor. The sombre (Eso and Eso-3J) and tobacco darkening (Etob) alleles, which both have dominant melanizing effects, results from point mutations that produce hyperactive MSH receptors. The Eso-3J receptor is constitutively activated, while the Etob receptor remains hormone responsive and produces a greater activation of its effector, adenylyl cyclase, than does the wild-type allele. PMID- 8458080 TI - A novel divalent cation-binding site in the A domain of the beta 2 integrin CR3 (CD11b/CD18) is essential for ligand binding. AB - A recombinant peptide encoding the CD11b A domain bound 54Mn2+ with a high affinity. Other divalent cations, including Mg2+, Zn2+, Ni2+, Co2+, and Cd2+, but not Ca2+ or Ba2+, competed effectively for Mn2+ binding. Amino acid substitutions within two conserved and noncontiguous regions in the recombinant peptide abolished 54Mn2+ binding. When these substitutions were introduced independently in complement receptor type 3 (CR3), each abolished the metal-dependent binding of the receptor to the major C3 opsonin iC3b, without impairing subunit association or surface expression of the receptor. These findings identify an unsuspected and novel metal-binding site within the A domain of CR3 that is required for metal-dependent ligand binding and also identify a good target for designing drugs aimed at countering the inflammatory potential of this key receptor. PMID- 8458081 TI - Segregation of storage protein mRNAs on the rough endoplasmic reticulum membranes of rice endosperm cells. AB - Developing rice endosperm cells display two distinct rough endoplasmic reticula (ER), cisternal ER (C-ER) and protein body ER (PB-ER), the latter delimiting the prolamine protein bodies. These ER membranes are utilized for the simultaneous synthesis of glutelin and prolamine storage proteins, which are subsequently routed into separate protein bodies. We demonstrate by blot hybridization, and by visualization of the spatial distributions and densities of these transcripts in endosperm cells via high resolution in situ hybridization analysis, that prolamine transcripts are associated primarily with the PB-ER, while glutelin mRNAs are enriched on the C-ER. The results suggest that the initial targeting process of these storage proteins into distinct protein bodies is the segregation of their transcripts on the ER membranes. PMID- 8458082 TI - The human U1 snRNP-specific U1A protein inhibits polyadenylation of its own pre mRNA. AB - Human, mouse, and Xenopus mRNAs encoding the U1 snRNP-specific U1A protein contain a conserved 47 nt region in their 3' untranslated regions (UTRs). In vitro studies show that human U1A protein binds to two sites within the conserved region that resemble, in part, the previously characterized U1A-binding site on U1 snRNA. Overexpression of human U1A protein in mouse cells results in down regulation of endogenous mouse U1A mRNA accumulation. In vitro and in vivo experiments demonstrate that excess U1A protein specifically inhibits polyadenylation of pre-mRNAs that contain the conserved 3' UTR from human U1A mRNA. Thus, U1A protein regulates the production of its own mRNA via a mechanism that involves pre-mRNA binding and inhibition of polyadenylation. PMID- 8458083 TI - Splice site choice and splicing efficiency are positively influenced by pre-mRNA intramolecular base pairing in yeast. AB - Many of the mechanisms that govern splice site selection and splice site partner assignment during pre-mRNA splicing are obscure. To address this problem, we analyzed the splicing of transcripts containing chimeric introns or splice site duplications derived from two natural yeast genes. Our experiments indicate that there are strong context effects that influence splicing efficiency and relative splice site strength. Cis-competition experiments showed that the context effects are not only local, as the source of the 3' splice site region influences 5' splice site selection and the source of the 5' splice site affects 3' splice site selection. A significant fraction of the long-range context effect appears to be due to base pairing between two intronic regions near the 5' splice site and branchpoint, an interaction that positively affects splicing efficiency as well as splice site selection. PMID- 8458084 TI - RNA-dependent replication, transcription, and persistence of brome mosaic virus RNA replicons in S. cerevisiae. AB - This paper shows that yeast can be a host for the replication of a higher eukaryotic viral genome. Brome mosaic virus (BMV) is a member of the alphavirus like superfamily of animal and plant positive strand RNA viruses. Yeast expressing BMV RNA replication genes 1a and 2a support RNA-dependent replication and transcription of BMV RNA3 derivatives. RNA3 derivatives with the coat gene replaced by a reporter gene expressed that gene in a fashion dependent on 1a and 2a expression in trans and on BMV RNA replication and transcription signals in cis. RNA3 derivatives carrying the yeast URA3 gene complemented ura3- yeast to prototrophy and were maintained as persistent RNA episomes. Thus, all cellular factors essential for BMV RNA replication and transcription must be present in yeast, and yeast genetics should facilitate their identification. PMID- 8458085 TI - A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group. AB - The Huntington's disease (HD) gene has been mapped in 4p16.3 but has eluded identification. We have used haplotype analysis of linkage disequilibrium to spotlight a small segment of 4p16.3 as the likely location of the defect. A new gene, IT15, isolated using cloned trapped exons from the target area contains a polymorphic trinucleotide repeat that is expanded and unstable on HD chromosomes. A (CAG)n repeat longer than the normal range was observed on HD chromosomes from all 75 disease families examined, comprising a variety of ethnic backgrounds and 4p16.3 haplotypes. The (CAG)n repeat appears to be located within the coding sequence of a predicted approximately 348 kd protein that is widely expressed but unrelated to any known gene. Thus, the HD mutation involves an unstable DNA segment, similar to those described in fragile X syndrome, spino-bulbar muscular atrophy, and myotonic dystrophy, acting in the context of a novel 4p16.3 gene to produce a dominant phenotype. PMID- 8458086 TI - [Hormonal changes in open-angle glaucoma. I. Levels of immunoreactive insulin in serum]. AB - This paper deals with the relation of disorders of carbohydrate metabolism to etiopathogenesis of glaucoma. 102 patients with primary glaucoma of an open angle were examined and it was discovered that 80 patients from this group (78%) had an abnormal immuno-reactive insulin curve, in particular of the hypersecretory type. Standard gauge test for abnormal glucose level was administered with 31 glaucomatous patients (30%). From this point of view screening for immuno reactive insulin is a more sensitive and reliable method than the glucose standard gauge test. It is recommended that testing for immuno-reactive insulin should be introduced for all glaucomatous patients because this can help both in the detection of early stages of diabetes and in the administration of primary prevention of atherosclerosis among the population. PMID- 8458087 TI - [Hormonal changes in open-angle glaucoma. II. Levels of cortisol and somatotropin in serum]. AB - Observing interrelation between carbohydrate metabolism disorders and contrainsular mechanisms in a group of 102 glaucomatous patients, a higher level of cortisol in plasma was detected in 40.2% of glaucomatous patients of whom 31% had increased levels of cortisol together with IRI. In isolation the increased level of cortisol occurred in 8.9%. The frequency of increased cortisol level in glaucomatous patients is substantially lower (40.2%) than the frequency of abnormal insulin curves (78%). Increased levels of growth hormone in the group of patients occurred in 9.3% of cases and these were almost always associated with an abnormal immuno-reactive insulin curve (IRI curve). Accordingly, it is evident that hormonal disorders are a major factor in the onset of both diabetes and glaucoma. PMID- 8458088 TI - [Dynamics of retinal changes in relation to treatment of Waldenstrom's macroglobulinemia]. AB - Authors document with the aid of fluorescent angiography of the retina pathological changes on the retina resulting from hyperviscous syndrome of Waldenstrom macroglobulinemia and their regulation after combined treatment with plasmapheresis and cytostatics. PMID- 8458089 TI - [Factors influencing the effectiveness of argon laser trabeculoplasty]. AB - The effectiveness of argon laser trabeculoplasty in managing the primary open angle glaucoma was observed in 103 patients (202 eyes) in period of 3 years. The authors are confirming its good effects, the maximum of it in three months after the trabeculoplasty. The best response was achieved in patients with the preoperative intraocular pressure lower than 25 mmHg and in the age group above 60 years. To obtain the good results after the operation in 87.12% of patients the local medical treatment was necessary, although in 51.98% the medication was reduced. The effectiveness of operation was decreasing with time, in 2 years was just 56.93% and in three years 23.27%. The significant improvement of outflow facility was observed in 85% of cases by electrotonography. PMID- 8458090 TI - [Correlation between various methods of examination in glaucoma]. AB - The authors investigated a group of 42 patients (84 eyes) with primary glaucoma of the open angle and with glaucoma of a low tension. In addition to the basic examination they applied in all patients fluorescent angiography focused on the papilla of the optic nerve, static computer threshold perimetry using a Humphrey Field Analyzer, strategy 30-2, examination of the colour sense (Farnsworth Munsell 100 HUE test and the desaturated HUE test with computer analysis) and examination of contrast sensitivity by means of the Cambridge low contrast test. They describe the results in the initial stage of an at least 5-year study. In patients aged 41-50 years (n = 10) they found small paracentral scotomas in the visual field in 90% and arcuate scotomas in 10%, minor absolute defects of filling of the papilla in 85%, in 15% only relative defects. In patients aged 51 60 years (n = 15) they revealed acute scotomas in 73% and marked quadrant losses in 27%. Changes in the fluoroangiogram were more marked than in the former groups. In patients aged 61-71 years (n = 15) the changes were analogous. Defects of colour sense of the blue-yellow area were recorded in 63 eyes. Changes of the colour sense and absolute defects of filling in fluorescent angiography correlated with the degree and site of affection of the visual field and the patient's age in primary open angle glaucoma. Conversely, in glaucoma with normal tension the values of colour sense remained normal even when the visual field was affected. PMID- 8458091 TI - [Glaucoma. Historical overview]. PMID- 8458092 TI - [Report of Th. Leber, an ophthalmologist, from the battlefield in Hradce Kralove in 1886]. PMID- 8458093 TI - [Abnormal vessels in the iris in angiographic imaging]. AB - During the examination of 210 eyes with blue irises by fluorescein angiography a few unusual vascular formations of the course, filling and caliber were revealed. Authors have divided them into four groups by similar angiographic pictures. Possible capillary haemangioma in connection with syndrome Sturge-Weber from the third group and angioma racemosum from the fourth group of examined irises are considered to be abnormal vessels. It is possible to state diagnosis by fluorescein angiography in many cases even without histological examination and to follow the dynamics of their possible development. PMID- 8458094 TI - Thyroid hormone resistance syndromes--are generalized and selective pituitary resistance part of the same disorder? PMID- 8458095 TI - Impaired thermoregulation in adults with growth hormone deficiency during heat exposure and exercise. AB - OBJECTIVE: It has recently been shown that patients with growth hormone deficiency have a reduced sweating capacity. We hypothesize that reduced sweating might affect thermoregulation in growth hormone deficiency patients. In the present study we have examined thermoregulation in growth hormone deficiency patients. DESIGN AND PATIENTS: Six adult growth hormone deficiency patients and six matched controls were exposed to a 90-minute heat period (40 degrees C). On a second day the subjects exercised for 30 minutes under standardized conditions. MEASUREMENTS: On both occasions changes in GH secretion, sweating and temperature were registered. Heat storage and evaporation were calculated from these data. RESULTS: We found that during the moderate heat exposure, evaporation was less (56.7 vs 115.6 W, P = 0.0037) and heat storage greater (60.7 vs 37.0 W, P = 0.025) in growth hormone deficiency patients compared to their matched controls. Two of the six patients reacted with severe clinical symptoms of heat exhaustion, whereas the controls were unaffected. After exercise the patients reached significantly higher core temperatures than their matched controls (38.1 vs 37.8 degrees C, P = 0.0097). CONCLUSIONS: Thus, our findings are indicative of a reduced thermoregulatory function in some patients with GH deficiency. PMID- 8458096 TI - Blood pressure and the renin-angiotensin-aldosterone system in children receiving recombinant human growth hormone. AB - OBJECTIVE: We investigated the effect of growth hormone (GH) treatment on salt and water metabolism and the renin-angiotensin-aldosterone system in children with short stature. DESIGN: Randomized, controlled study. PATIENTS: Twenty-nine short, pre-pubertal children referred to two specialist growth clinics for further assessment. MEASUREMENTS: Serial measurements of blood pressure, body weight, plasma renin activity (PRA), aldosterone, electrolytes, insulin and insulin-like growth factor I (IGF-I) have been made following the initiation of GH treatment. RESULTS: A small and transient increase in systolic blood pressure was observed during the first week of GH treatment. The increase in blood pressure over baseline was -1.1 mmHg in controls compared to +11.5 and +3.0 mmHg in children receiving standard (20 units/m2/week) and high dose (40 units/m2/week) GH respectively (P = 0.004). Over the same time interval body weight also tended to increase with GH compared with controls. These changes were greater in those children receiving the lower dose of GH and were not significantly related to age or prior GH status. PRA did not change with GH treatment. Although plasma aldosterone concentration tended to increase with GH, maximal values did not differ from controls and all remained within our normal range. Plasma IgF-I levels were increased by a similar amount in both treatment groups (1.5 and 1.12 U/ml compared to 0.44 U/ml in controls at 4 months). No difference in plasma insulin concentration was noted after 7 days of GH. CONCLUSIONS: In contrast to adult subjects, treatment with high dose GH in childhood is not associated with activation of the renin-angiotensin-aldosterone system. Clinical signs consistent with transient salt and water retention are observed with GH therapy, however, suggesting either a direct effect of GH or of IGF-I on renal tubular function. Blood pressure, plasma renin activity and plasma aldosterone levels were not increased after more prolonged GH therapy. These data suggest that high dose GH therapy in childhood is unlikely to be associated with the increased risk of hypertension seen in adults with GH hypersecretion. PMID- 8458097 TI - Influence of spontaneous or induced puberty on the growth promoting effect of treatment with growth hormone in girls with Turner's syndrome. AB - OBJECTIVE: The aim was to evaluate the effect of 3 years treatment with recombinant human growth hormone (rhGH) on height velocity and height in girls with Turner's syndrome (TS) and to study to influence of spontaneous or induced puberty on the growth promoting effect of rhGH. PATIENTS AND DESIGN: The investigation was performed in 36 girls with Turner's syndrome treated for 3 years with rhGH in a dose of 1 IU/kg week, administered as daily subcutaneous injections. Fifteen patients remained prepubertal throughout the observation period (Group 1). During the first 2 years of rhGH therapy, four girls developed puberty spontaneously (Group 2). During the 3rd year of rhGH treatment puberty was induced with 100 ng/kg day ethinyl oestradiol orally in 17 girls requesting pubertal development and with a bone age of at least 11 'years' (Group 3). RESULTS: During the first year of rhGH therapy height velocity increased significantly in all patients. Mean +/- SD height velocity was higher in the four patients with Turner's syndrome who developed spontaneous puberty than in 17 age matched girls with Turner's syndrome without puberty (8.9 +/- 1.2 vs 7.4 +/- 1.2 cm/year; P < 0.05). During the second and third year of rhGH treatment height velocity decreased in all patients but remained above baseline levels. The induction of puberty with 100 ng/kg day ethinyl oestradiol in the patients of Group 3 did not lead to an acceleration of height velocity, but seemed in contrast to decelerate height velocity. After 3 years of rhGH treatment, 21 out of 36 patients have obtained a height at or above the initially calculated projected adult height and five girls are already taller than 150 cm. CONCLUSIONS: The onset of spontaneous puberty during the first years of rhGH treatment seems to have an additive effect to rhGH on height velocity. Induction of puberty with oral administration of 100 ng/kg day ethinyl oestradiol did not have any beneficial effect on height velocity and seems therefore not to be the optimal way to induce puberty with an adequate pubertal growth spurt in girls with Turner's syndrome under rhGH therapy. Different doses and routes of oestrogen administration have to be evaluated in order to mimic the growth promoting effect of spontaneous puberty as well as possible. PMID- 8458098 TI - A role for life events in the pathogenesis of Cushing's disease. AB - OBJECTIVE: We have previously reported on 30 patients with Cushing's syndrome suggesting an aetiological role for stressful life events. The investigation about life events in the year before the first signs of disease onset was extended to a larger population of patients with Cushing's syndrome, allowing us to differentiate patients with pituitary-dependent and pituitary-independent forms. DESIGN: Case-control study. PATIENTS: Sixty-six consecutive patients with Cushing's syndrome of various aetiologies (46 with pituitary-dependent forms and 20 with primary adrenal hyperfunction or ectopic ACTH production) and a control group of 66 healthy subjects, matched for sociodemographic variables, were studied. MEASUREMENTS: Paykel's Interview for Recent Life Events (a semistructured research interview covering 64 life events) was administered after the acute phase of illness while in remission. RESULTS: Patients with Cushing's syndrome reported significantly more stressful life events (P < 0.001), both events that had an objective negative impact (P < 0.001) and independent events (P < 0.001), than controls, confirming previous findings. Patients with pituitary dependent Cushing's disease were compared with their matched controls and reported significantly more total events, events with an objective negative impact and independent events (all at P < 0.001). There were no significant differences between patients with pituitary-independent forms and their matched controls. CONCLUSIONS: These findings indicate a causal role for stressful life events exclusively in pituitary-dependent Cushing's disease, and suggest a limbic hypothalamic involvement in the pathogenesis of this condition. The results are similar to those obtained in major depression, and add to other analogies between the two disorders. PMID- 8458099 TI - Screening for thyroid diseases in an iodine sufficient area with sensitive thyrotrophin assays, and serum thyroid autoantibody and urinary iodide determinations. AB - OBJECTIVE: The present study was designed to investigate the prevalence of thyroid dysfunction and its relation to thyroid autoantibodies and urine iodide concentration in apparently healthy people residing in Sapporo, a city of northern Japan, where the iodine intake is high. DESIGN AND SUBJECTS: Serum TSH and thyroid autoantibodies, and urine iodide were measured in 4110 people (2931 men and 1179 women) (age 45.6 +/- 10.3 years (mean +/- SD)) who were recruited at the hospital for medical examinations. RESULTS: The thyroid autoantibodies were positive in 6.4% of males and 13.8% of females with an age-related increase. Of the people with positive antibodies, 87.2% had normal TSH values (0.15-5.0 mU/l) as measured by a sensitive assay. The prevalence of unsuspected hyperthyroidism as defined by suppressed TSH values was 0.61%, of which 64% was diagnosed as Graves' disease based on positive thyrotrophin receptor antibody results. The prevalence of unsuspected hypothyroidism, as evidenced by supranormal TSH, was 0.68% for males and 3.13% for females with an age-related increase. Of those with hypothyroidism, 45.5% were autoantibody positive. The overall prevalence of Hashimoto's thyroiditis was 13.11% for females and 6.15% for males. The urine iodide levels of hypothyroidism with a positive autoantibody of 38.5 (17.7-83.9) mumol/l and a negative autoantibody of 34.9 (17.9-67.9) mumol/l were both significantly higher than that of normal subjects (26.9 (14.6-49.6) mumol/l) (P < 0.01). When iodine intake was restricted for 6-8 weeks for hypothyroid subjects, the elevated TSH and thyroglobulin and low free T4 levels were reversed in the autoantibody negative but not in the positive group. CONCLUSIONS: This study provides further information on the prevalence of thyroid dysfunction and autoimmune thyroid diseases in an iodine sufficient area. In addition, it suggests that more than half of the patients with unsuspected hypothyroidism were negative for autoantibodies and that the excessive iodine intake may be involved in causing latent hypothyroidism. PMID- 8458100 TI - Molecular forms of parathyroid hormone-related protein in tumours and biological fluids. AB - OBJECTIVE: We investigated the content and compared the molecular forms of parathyroid hormone-related protein in tumour tissue, plasma and pleural fluid. DESIGN: Measurement of parathyroid hormone-related protein in tumour extracts and biological fluids and comparison of the elution profiles of parathyroid hormone related protein (PTHRP) immunoreactivity following gel filtration chromatography on Bio-gel P100. PATIENTS: Tumours and plasma from patients with humoral hypercalcaemia of malignancy were studied, together with tumours and pleural fluids from patients who were normocalcaemic. MEASUREMENTS: Immunoreactivity in column fractions, plasma and tumour extracts was measured by a highly sensitive immunoradiometric assay for PTHRP 1-86 with specificity directed at the 17-61 region of PTHRP. RESULTS: Similar levels of PTHRP immunoreactivity were measured in tumours from normocalcaemic and hyper-calcaemic patients. PTHRP 1-86 (28-4630 fmol/g) was detected in eight of the nine tumours studied. Immunoreactivity in tumour extracts eluted as major peaks in the range 22-33 kDa with an additional peak of 15 kDa in three out of six tumours studied. In contrast, immunoreactivity in plasma and pleural fluid eluted within the range 7-14 kDa. CONCLUSIONS: The major species of parathyroid hormone-related protein in plasma and pleural fluids was consistently smaller than that in tumour tissue (22-33 kDa) suggesting that tumour-derived parathyroid hormone-related protein is processed at the COOH terminus to form a species of approximately 10 kDa which circulates in patients with humoral hypercalcaemia of malignancy. PMID- 8458101 TI - The relation between clinical manifestations of polycystic ovary syndrome and beta-cell function. AB - OBJECTIVE: Hyperandrogenism in patients with polycystic ovary syndrome has been shown to correlate with hyperinsulinaemia of insulin resistance. We have investigated if basal levels of insulin and the response to the intravenous administration of glucagon can reveal insulin resistance in patients with polycystic ovary syndrome. PATIENTS: Nine obese (BMI > 25 kg/m2) and nine non obese (BMI 19-25 kg/m2) women with PCOS, chosen from a population of 91 women attending the infertility clinic, and 19 normally cycling women (seven obese, 12 non-obese) were studied. Oligo or amenorrhoea, hirsutism, and 12 or more follicles in a given ovary were selection criteria. MEASUREMENTS: Glucagon, 1 mg, was given intravenously to 18 of the 91 women and to the control subjects. Blood was taken at -5, 0, 5, 10 and 15 minutes for measurements of integrated areas under the response curve for insulin, C-peptide and glucose, respectively. Basal blood samples were drawn for fasting insulin, C-peptide, glucose, testosterone, sex hormone-binding globulin (SHBG), free fatty acids and IGF-I measurements. The free androgen index was calculated according to the formula FAI = testosterone x 100/SHBG. RESULTS: There were no significant differences in maximal increment and area under the response curve for glucose, C-peptide and insulin. FAI was significantly higher in all patients with features of polycystic ovary syndrome. However, fasting insulin levels were significantly higher only in obese patients when compared with obese control subjects and lean patients. CONCLUSIONS: The administration of 1 mg glucagon i.v. did not distinguish patients with polycystic ovary syndrome from control subjects. The mild insulin resistance of polycystic ovary syndrome is related only to obesity and is therefore unlikely to play an important role in the hyperandrogenism associated with the syndrome. PMID- 8458102 TI - Inhibin and follicle-stimulating hormone levels in gonadotroph adenomas: evidence of a positive correlation with tumour volume in men. AB - OBJECTIVE: Gonadotroph adenomas are generally revealed by symptoms of mass effect at the stage of macroadenoma. Most of them hypersecrete FSH and/or gonadotrophin subunits. Rarely they hypersecrete LH, which could induce endocrinological symptoms. As the glycoprotein inhibin is secreted by the gonads under FSH control, we have evaluated whether high immunoreactive inhibin (iINH) levels correlated with FSH hypersecretion and whether iINH and FSH levels were related to tumour volume in subjects with gonadotroph adenomas. PATIENTS: Forty-five patients (30 men, 15 women) were retrospectively selected on the basis of immunostaining technique using specific antibodies raised against FSH-beta, LH beta and glycoprotein alpha-subunit. MEASUREMENTS: Immunoreactive inhibin (iINH) was measured by radioimmunoassay using antiserum 1989 raised to bovine inhibin. Tumour volume index was the product in cm3 of length, width and height of the adenoma as assessed by computerized tomography. RESULTS: In men (age 21-61 years), iINH levels were positively correlated with FSH levels (Spearman's r = 0.67, P < 0.001), and both iINH and FSH levels were significantly correlated with tumour volume index (Spearman's r = 0.38, P < 0.05 and r = 0.39, P < 0.05 respectively). In the subgroup of men with normal FSH levels (n = 17), the correlation of FSH with tumour volume index was high: Spearman's r = 0.56, P < 0.05. In the post-menopausal women (n = 8, age > 55 years), iINH levels were undetectable or below the follicular phase range regardless of FSH values. In the premenopausal women (n = 7, age 22-49 years, follicular phase or amenorrhoea) iINH levels were above follicular phase range in three women including one who had very high FSH levels. CONCLUSIONS: These data show that in men with gonadotroph adenoma FSH levels are related to tumour mass and suggest that a significant part of circulating FSH in patients with normal FSH levels arises from the tumour. The significant correlation between iINH and FSH levels demonstrates that tumoral FSH is bioactive and that high iINH levels do not exert any feedback control on tumoral FSH secretion. Therefore the coexistence of high FSH levels with high iINH levels is strongly suggestive of a gonadotroph adenoma. Gonadotroph adenomas seem to represent a unique model of long-term FSH stimulation of inhibin-producing cells, in some way analogous to that created by repetitive administration of exogenous FSH. PMID- 8458103 TI - Serum FSH bioactivity and response to acute gonadotrophin releasing hormone (GnRH) agonist stimulation in patients with polycystic ovary syndrome (PCOS) as compared to control groups. AB - OBJECTIVE: We evaluated the biological activity of FSH in the serum of women with polycystic ovary syndrome before and after acute administration of a GnRH agonist as compared to control groups. DESIGN: FSH, oestradiol and androstenedione response to buserelin (100 micrograms s.c.) comparing seven polycystic ovary patients, six idiopathic hirsute women, 11 normal women in the follicular phase and nine normal men. MEASUREMENTS: Rat granulosa cell aromatase bioassay in the presence or absence of polyethyleneglycol (PEG) pretreated 2% serum. Serum biological FSH (B-FSH), immunological FSH (I-FSH) and B/I ratio at times 0, 1, 2, 3, 4, 8, 12 and 24 hours. Serum androstenedione and oestradiol at times 0 and 24 hours. RESULTS: Human gonadotrophin-free (oral contraceptive user and after FSH immunoabsorption) and PEG-pretreated serum increases the aromatase activity in response to increasing doses of purified FSH. The maximum enzymatic activity is however higher with 2% serum than with 4% serum. The amplitude of the B-FSH response to the GnRH agonist is markedly decreased in the polycystic group as compared to the group of normal women. There is also a small decrease in the I FSH response in the polycystic women. When compared to that of normal women, the area under the curve in the polycystic ovary patients is reduced by 71% for B-FSH (P < 0.01) and by 23% for I-FSH (P < 0.05). The B-FSH and I-FSH responses in men are very small. After an initial decrease the B/I ratio returns to baseline level in normal women but remains low in the other groups. At time 24 hours, there is no significant change in the serum concentration of androstenedione but serum oestradiol, the baseline of which is significantly higher in the polycystic patients than in normal women, is also significantly higher at 24 hours (P < 0.05) in response to the pharmacological release of FSH. CONCLUSION: The gonadotrophin-free and PEG-pretreated human serum has an inherent stimulatory effect on the rat granulosa aromatase bioassay with a higher activity at 2% serum. Acute GnRH agonist stimulation reveals a deficiency in the FSH response in polycystic ovary patients. The greater deficit in B-FSH than in I-FSH would indicate a possible modification in the FSH isoforms in this syndrome. The meaning of this observation for the understanding of the physiopathology of the polycystic ovary syndrome remains to be evaluated. PMID- 8458104 TI - Endothelin-1 receptors in the human myometrium: evidence for different binding properties in post-menopausal as compared to premenopausal and pregnant women. AB - OBJECTIVE: We investigated the binding properties of the endothelin receptors in the human myometrium in clinical situations associated with different ovarian steroid levels. SUBJECTS AND METHODS: Binding properties of the endothelin receptors were studied in myometrial membranes from post-menopausal women (n = 12), myomatous premenopausal women (n = 14) and pregnant women (n = 14), using 125I-labelled endothelin-1. RESULTS: The mean (+/- SD) maximal receptor density (Bmax) was significantly higher in samples from premenopausal and pregnant women than from post-menopausal women (983 +/- 196, 1116 +/- 201 and 490 +/- 145 pmol/g protein, respectively). Receptor affinity (Kd) did not differ significantly between these groups. Among the pregnant women, mean Bmax and Kd values were similar in those who electively underwent Caesarean section prior to the onset of labour and those operated on during the second stage of spontaneous labour. Binding properties of myometrial membranes of either pre or post-menopausal women were unaffected by the presence of high levels of beta-oestradiol or progesterone in the medium. Among samples of premenopausal women, no significant difference was found in binding properties between those operated on either during mid follicular phase or during mid-luteal phase. CONCLUSIONS: In clinical situations associated with relatively high levels of ovarian steroids, the density of endothelin receptors in the myometrium is higher than in situations associated with low ovarian steroid level. Ovarian steroids may exert their influence via the production of other mediators. Changes in density of the endothelin receptor, induced by change in ovarian steroids activity, might play a role in the regulation of myometrial contractility. PMID- 8458105 TI - Polycystic ovaries are a common finding in untreated female to male transsexuals. AB - OBJECTIVE: We studied the pretreatment hormone profile and ovarian ultrasound appearance of female-to-male transsexuals. DESIGN: Female-to-male transsexuals who were seen in the local Gender Identity Clinic were examined after psychiatric assessment. RESULTS: Sixteen patients were assessed. Approximately 50% had symptoms and signs of the polycystic ovary syndrome (PCOS) and 15 had a pelvic ultrasound diagnosis of polycystic ovaries. The endocrine profiles of the patients were not markedly abnormal and were compatible with the diagnosis of PCOS. CONCLUSIONS: Polycystic ovaries and the polycystic ovary syndrome are a common finding in female-to-male transsexuals who have had no previous exposure to exogenous androgen therapy. PMID- 8458106 TI - A case of papillary carcinoma of the thyroid with more than 30 years long-term asymptomatic pulmonary metastases. AB - This is a case report of a patient with thyroid cancer with asymptomatic pulmonary metastases, and without obvious progression over 34 years. The patient, a 47-year-old male, was shown to have miliary shadows on chest radiographs from the age of 13; indeed, he was temporarily treated for pulmonary tuberculosis without success. A tumour appeared in the right neck in December 1988 (at age 47). A diagnosis of lymph node metastasis of papillary carcinoma of the thyroid was made by biopsy; he then underwent total thyroidectomy with radical dissection of the neck (April 1989). However, the bilateral metastatic lymph nodes in the neck had invaded the vasculature, preventing complete dissection. Post-operative whole body 131I scintigraphy revealed diffuse intensive uptake in the bilateral lung fields, demonstrating for the first time that the pulmonary lesions were metastases of the thyroid cancer. He remains under periodic effective treatment with 131I. PMID- 8458107 TI - Re-operations for coronary artery disease. PMID- 8458108 TI - Intravenous thrombolytic therapy in myocardial infarction: an analytical review. AB - The properties and physiological effects of three currently FDA-approved thrombolytic agents, streptokinase (SK), tissue plasminogen activator (tPA), and anisoylated plasminogen activator complex (APSAC) are reviewed. All thrombolytic agents have been shown to reduce mortality postmyocardial infarction (MI). Comparative trials have failed to demonstrate a difference between the effects of tPA, SK, and APSAC on mortality. In addition, no consistent difference between the three agents on ejection fraction (EF) has been found despite a superior reperfusion rate with tPA at 90 min. Furthermore, reinfarction and interventional procedure rates were significantly higher after thrombolytic treatment, and the incidence of total strokes was higher with tPA than SK in some comparative studies. Based on analysis of the published megatrials, SK is a more cost effective thrombolytic agent for patients with acute MI than tPA or APSAC. PMID- 8458109 TI - Treatment of hypertension with felodipine in patients with concomitant diseases. AB - Coexisting medical conditions often complicate the selection of antihypertensive drugs. Felodipine, a new vascular-selective calcium antagonist with demonstrated antihypertensive efficacy, has not been found to alter lipid profiles in hypertensive patients. Studies in additional patient populations have yielded insights into the effects of the drug on other diseases that may coexist with hypertension. In individuals with stable angina pectoris or congestive heart failure, acute administration of felodipine reduces systemic vascular resistance and increases cardiac output and total coronary blood flow; myocardial contractility is not depressed at doses that produce a clinically significant reduction in vascular resistance. In patients with coronary stenoses, the drug increases vessel diameter in the vicinity of obstructive lesions. Single-dose and long-term studies in patients with exertional angina have found that felodipine reduces anginal frequency and improves exercise tolerance. In patients with congestive heart failure, chronic dosing with felodipine produces a persistent reduction in vascular resistance and an increase in cardiac output, both at rest and during exercise. Symptomatic improvement and increased exercise tolerance have been noted in some studies. In patients with Raynaud's phenomenon, felodipine has been associated with a dose-dependent improvement in symptomatology. Among individuals with exercise-induced bronchospasm, the drug has no effect on resting bronchial tone and may exert some positive effects during exercise. In hypertensive patients with Type II diabetes, felodipine has not been found to raise glucose levels significantly. The data obtained thus far suggest that felodipine is safe for use in hypertensive patients with a variety of concomitant diseases. PMID- 8458110 TI - Dose-ranging study with a new two-chain rt-PA in patients with acute myocardial infarction: a multicenter trial. AB - Tissue-type plasminogen activator (t-PA) derived from a melanoma cell line was first used in patients with acute myocardial infarction in the early 1980s. Recombinant DNA technology then allowed production of large amounts of t-PA. The TIMI-I trial used a two-chain recombinant (rt-PA) product. A predominantly single chain rt-PA (alteplase) was used in the majority of the TIMI II trial. The present study used a different form of two-chain rt-PA (duteplase) to determine the effective dose for thrombolysis at 60 min, and to evaluate time to reperfusion, reocclusion at 72-96 h, coagulation profiles, and bleeding events. Duteplase was given intravenously to 75 patients a mean of 3.8 +/- 1 h after the onset of myocardial infarction. Following angiography demonstrating coronary occlusion, 23 patients received a low dose of duteplase [0.16-0.29 million international units per kilogram (MIU/kg)] over 60 min followed by a 5-h infusion in conjunction with heparin, 25 patients received a middle dose (0.30-0.41 MIU/kg) and 23 patients received a high dose (0.43-0.74 MIU/kg). Angiography was then performed every 15 min x 4. Progressive recanalization occurred over 60 min (median 45 min) with an overall success rate of 59% (mean 60-min dose: 0.37 MIU/kg). No dose-response relationship was observed. The reocclusion rate was 9% at 72-96 h. Reductions in fibrinogen and plasminogen correlated with dose, but clinical events did not.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458111 TI - Single site experience with high-speed coronary rotational atherectomy. AB - This report describes a single site experience as part of a multicenter clinical trial with high-speed rotational atherectomy in human coronary arteries. A total of 108 patients with 143 lesions had interventions, were grouped by success or failure, and were analyzed by patient, lesion, and procedural variables. Satisfactory results were achieved in 131 of 143 lesions (92%) and 99 of 108 (92%) patients. Neither patient-related variables (age, gender, diabetes, hypertension, cigarette use, restenosis, previous myocardial infarction, and left ventricular function) nor lesion characteristics (length, ostial or bifurcation location, calcification, lesion classification, and coronary location) were predictive of poor outcome. Tears, acute closure, percentage stenosis after rotational atherectomy and after adjunctive balloon angioplasty were the procedural variables that were statistically associated with outcome by univariate methods. Multivariate analysis isolated postintervention residual stenosis as the only variable that was statistically different between groups. Serious complications included one death in the catheterization laboratory, one Q wave myocardial infarction, three non-Q myocardial infarctions, and three emergency coronary bypass operations for sustained vessel closure. One patient required emergency surgery for a pacing wire perforation not related to the use of the device. The potential benefits of high-speed rotational atherectomy include increased safety in complex lesions, the ability to address lesions not amenable to balloon techniques, and the possibility of reducing the incidence of restenosis. PMID- 8458112 TI - Simvastatin in severe primary hypercholesterolemia: efficacy, safety, and tolerability in 595 patients over 18 weeks. The Principal Investigators. AB - We report the results of an open multicenter study which evaluated the efficacy, safety, and tolerability of simvastatin in a large cohort of patients with primary hypercholesterolemia. Against a background of standard dietary advice, the study enrolled 595 patients with total cholesterol > or = 6.5 mmol/l and triglycerides < 6.0 mmol/l across 20 centers. After 4 weeks on placebo, treatment began with simvastatin 10 mg each night, titrating to 20 mg after 6 weeks, and then to 40 mg after 12 weeks if cholesterol levels still exceeded 5.5 mmol/l. By Week 18, 70% of patients were using 40 mg/day. After 18 weeks of treatment, the mean reductions (95% confidence interval) in total and low density lipoprotein (LDL) cholesterol were 30% (29-31%) and 38% (37-39%), respectively. There was a mean increase in high density lipoprotein (HDL) cholesterol of 12% (10-13%), while triglycerides were reduced by a median 19% (16-23%). From a mean entry total cholesterol of 9.31 +/- 2.15 mmol/l, 52% of patients achieved cholesterol levels < or = 6.2 mmol/l on treatment. The changes noted were essentially independent of gender, age, or lipid phenotype (IIa vs. IIb). Compliance with prescribed medication was very good and the drug was well tolerated; only 3% of patients manifested a clinical adverse experience requiring discontinuation or a clinical adverse experience described as serious (associated with hospitalization or serious disability). Isolated laboratory adverse experience required discontinuation in 0.2% of patients. One in 3 patients manifested a clinical adverse experience and 1 in 10 a laboratory adverse experience.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458113 TI - Fosinopril monotherapy: relationship between blood pressure reduction and time of administration. AB - The time to peak antihypertensive effect and the trough-to-peak ratio were determined in 64 Caucasian patients (19 men, 45 women) with mild to moderate hypertension [supine diastolic blood pressure (DBP) 95 to 115 mmHg]. They received placebo or fosinopril 10, 20, or 40 mg once daily for 4 weeks. The study consisted of a 4-week placebo lead-in, 4 weeks' double-blind treatment, and a 1 week placebo washout period. Vital signs were determined biweekly before dosing, and blood pressures were measured every 1 to 2 h during two 27-h periods at the beginning and end of treatment. After the first and last doses of all three regimens, the peak effect on blood pressure occurred 5 to 7 h after all three dosages. Neither peak nor trough blood pressure changes showed a clear dose response relationship. Trough to peak ratios for the first dose, corrected for placebo effects, were 79% for fosinopril 10 mg, 48% for fosinopril 20 mg, and 74% for fosinopril 40 mg, and the trough-to-peak ratios for the last dose were 41% for fosinopril 10 mg, 32% for fosinopril 20 mg, and 44% for fosinopril 40 mg. In the 38 responders among the 48 patients receiving fosinopril (supine DBP decrease of at least 5 mmHg at 24 h postdose), trough-to-peak ratios ranged from 50 to 81%, and the range indicates that fosinopril is efficacious when administered once daily. Adverse effects were mild to moderate, and no patient discontinued treatment. Changes in the laboratory test results, electrocardiograms, or the results of physical examinations were unremarkable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458114 TI - AAI pacing mode: when is it indicated and how should it be achieved? AB - AAI pacing offers better hemodynamic characteristics than dual-chamber pacing and is the optimal mode for patients with sick sinus syndrome without AV conduction disorders. AAI pacing may be achieved by single-chamber atrial pacing, by programming a dual-chamber pacemaker to the AAI mode, or by programming a dual chamber pacemaker to DDD mode with a long AV delay. The annual incidence of AV block development in patients with sick sinus syndrome is low, probably 1-5%, but there is no method of detecting patients immune or prone to future development of AV block. Chronotropic incompetence is often present in patients with sick sinus syndrome but the value of additional rate response is not yet firmly established. Our recommendations for the choice of the optimal method of pacing are discussed. PMID- 8458115 TI - Anatomy, histology, and pathology of the cardiac conduction system: Part II. AB - Normal anatomic and histologic features of the atrioventricular junction (transitional cell zone, atrioventricular node, penetrating portion of bundle) and the bifurcation of the penetrating portion into bundle branches are reviewed. Terminal ventricular Purkinje fibers are also discussed. PMID- 8458116 TI - The postcardiac injury syndrome following percutaneous transluminal coronary angioplasty. AB - A 57-year-old man, who had suffered an anterior Q-wave myocardial infarction complicated with typical post-cardiac injury syndrome (PCIS) 9 years earlier, underwent percutaneous transluminal coronary angioplasty (PTCA) without any immediate clinical, laboratory, or radiological signs of complications. After 4 days he recognized the recurrence of the earlier symptoms of PCIS. The diagnosis was supported by slight fever, elevated inflammatory parameters, and improvement when oral corticosteroids were given. The observations suggest that milder cardiac injury than previously considered, that is, without demonstrated structural damage to pericardium or myocardium, may precipitate PCIS in predisposed individuals. The case adds a differential diagnosis to chest pain and malaise following PTCA. PMID- 8458117 TI - Coronary artery rupture during transluminal coronary recanalization and angioplasty in a case of acute myocardial infarction and shock. AB - Percutaneous transluminal coronary angioplasty (PTCA) is a widely performed and effective therapy for coronary artery disease. Evolution of the dilatation instruments during the last decade has led to an increased success rate of PTCA and to the development of newer techniques such as recanalization of totally occluded coronary arteries. We report a case of coronary artery recanalization complicated by fatal coronary artery rupture. PMID- 8458118 TI - Giant dissecting aortic aneurysm with concealed perforation in an 81-year-old female. AB - This paper describes the history of an 81-year-old female suffering from a giant dissecting aortic aneurysm with concealed perforation within the thorax. The patient had suffered from arterial hypertension for about 10 years and had been treated with thiazide. Nine months prior to admission the patient was in a state of collapse, and ultrasound examination revealed an intra-abdominal aortic aneurysm. At this time thoracic x-ray showed aortic sclerosis and elongation of the aorta but no signs of aneurysm formation. After this episode the patient was symptom-free for the next 9 months. Following a further syncopal attack with severe thoracic pain, the patient was hospitalized at the intensive care unit. Both in thoracic x-ray and computed tomography of the thorax, a pronounced dissecting aortic aneurysm with perforation of the thoracic aorta into the mediastinum could be established. Because of the patient's poor general condition and advanced age, as well as far-reaching pathological findings, surgery was not advised by either the heart and vascular surgeon or the anesthetist. Following 1 week's intensive therapy, the patient's general condition improved greatly, with stabilization of thoracic pain, blood pressure, and respiratory action. On the other hand, thoracic x-ray, computed tomography, and magnetic resonance imaging produced a distinct progression of the aneurysm with consequent mild displacement of mediastinum and left lung. Laboratory examinations for syphilis showed no evidence of that disease. After further improvement the patient was discharged 4 weeks after admission and has been symptom-free for 6 months in spite of the extensive pathological findings described herein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458119 TI - Balloon dilatation of inferior vena cava obstruction in Budd-Chiari syndrome. AB - Budd-Chiari syndrome is a well described entity which can easily be confused with congestive hepatomegaly. The syndrome usually is caused by thrombosis of the hepatic veins, however it also can be caused by congenital fibrous webs that occlude hepatic vessels in the inferior vena cava. It leads to an enlarged liver with ascites, peripheral edema, and portal hypertension. PMID- 8458120 TI - Chuichi Kawai. PMID- 8458121 TI - Determinants of muscle function in the spastic lower extremity. AB - The upper motor neuron lesion that causes hemiplegia impairs the patient's selective control and exposes primitive modes of muscle activation. Significant inconsistency between the clinical findings and the patient's gait may result. Dynamic electromyography revealed the primitive mechanisms leading to these inconsistencies. The rate of stretch does not differentiate spasticity from contracture, since either a quick or slow stretch frequently causes a sustained muscle response. Using knee flexion to differentiate gastrocnemius and soleus spasticity is not reliable, since the change in neurologic input with flexion may inhibit the extensor muscle's response to stretch so that the soleus is also relaxed. The change in body position from lying supine to sitting can double the intensity of soleus spasticity, and standing further increases the tone. Primitive patterns of mass extension and flexion, while voluntary, inhibit normal progression during walking. Simultaneous activation of the soleus and gastrocnemius with the knee's quadriceps causes premature ankle plantar flexion as the limb is loaded in stance. The primitive flexion synergy between the hip, knee, and ankle (dorsiflexion) inhibits terminal swing knee extension while the hip remains flexed. Consequently, surgical planning for the hemiparetic limb must rely heavily on gait analysis findings (systematic observation or by instrumentation). PMID- 8458122 TI - Using dynamic electromyography to guide surgical treatment of the spastic upper extremity in the brain-injured patient. AB - Upper extremity deformity after brain injury is frequently complex and dominated by spasticity or contracture. Clinical examination of the limb is often difficult and inaccurate. Dynamic electromyography provides valuable information previously unobtainable. Analysis of this data can facilitate appropriate reconstruction of the deformed limb. PMID- 8458123 TI - Dynamic electromyography in functional surgery for upper limb spasticity. AB - Surgery to improve upper limb function after stroke, closed head injury, or other causes of acquired spasticity is generally accomplished by a combination of muscle transfer, lengthening, and/or release. Dynamic electromyography can be used to identify voluntary muscle action, delineate the deforming motor forces when spasticity is present, and provide guidance for surgical planning to improve prehensile hand function. PMID- 8458124 TI - Gait and posture changes in the Duchenne muscular dystrophy child. AB - As the child with Duchenne muscular dystrophy (DMD) grows older, gait and posture changes occur. This is attributable to the natural progress of muscle weakness secondary to muscle tissue destruction. Bracing improves body alignment and maintains limb stability passively. Surgical correction of contractures allows for bracing and maintenance function and is recommended as an adjunct to the overall care of the ambulatory DMD patient. PMID- 8458125 TI - Gait analysis. An essential tool in the treatment of cerebral palsy. AB - Gait analysis has radically changed the treatment of cerebral palsy. Preoperatively, it allows critical assessment of the specific pathologies of the patient. Postoperatively, it provides an accurate assessment of outcome. This assessment of outcome has in turn allowed the accurate critique of surgeries and has made it possible to discard treatments that are not useful or are perhaps even injurious. As a result of this continual reassessment of surgical techniques, several principles and insights regarding the treatment of cerebral palsy have been learned. These include (1) the importance of reestablishing normal gait prerequisites, (2) the methods of reducing the energy expenditure of the pathologic gait, (3) the importance of skeletal structures in providing the lever arm by which muscles produce moments around joints, (4) the role and importance of two joint muscles, and (5) the importance of separating abnormalities, which are emanating from the neurologic lesion, from secondary ("coping") responses. Through gait analysis, it has become apparent that diplegia and hemiplegia are noninclusive terms, each of which contain a variety of homogeneous patterns of gait. Eventually these patterns may be separated and identified and optimal treatment protocols for each pattern type developed. PMID- 8458126 TI - The use of the pathokinesiology laboratory to select muscles for tendon transfers in the cerebral palsy hand. AB - One hundred nine cerebral palsy hands referred for consideration for tendon transfers were examined clinically and by dynamic electromyography. Wire electromyography as used in gait analysis at the author's institution was employed in each of these cases. Most patients required transfers for release (opening) of the hand. The flexor carpi ulnaris and brachioradialis were the most common muscles active in release, yet even in those muscles, less than half were suitable for transfer. This suggests that the wire electromyogram is helpful in selecting the proper muscle for tendon transfer in the cerebral palsy hand. PMID- 8458127 TI - Common gait abnormalities of the knee in cerebral palsy. AB - Gait abnormalities in children with cerebral palsy are the consequence of contractures across joints, muscle spasticity, and phasically inappropriate muscle action. Though abnormalities involving one of the major joints of the lower extremity will usually have consequences on the function of the other joints, it is possible to recognize certain primary disorders at each joint. The most common gait abnormalities of the knee in patients with cerebral palsy occur in the sagittal plane. Based on the experience gained from performing gait analysis on more than 588 patients with cerebral palsy, four primary gait abnormalities of the knee have been identified: jump knee, crouch knee, stiff knee, and recurvatum knee. In this review, each abnormality is described by its motion analysis laboratory profile (physical examination, motion parameters, electromyography [EMG] data, and force plate data). The most common etiologies and the consequences for gait of each disorder are also considered. Appreciation of the most common pathologic patterns of gait should facilitate accurate and detailed analysis of the individual patient with gait abnormalities. PMID- 8458128 TI - Use of the pantaloon cast for the selection of fusion candidates in the treatment of chronic low back pain. AB - Forty-five patients with low back pain (LBP) of longer than six months' duration and for whom all conservative therapies failed were placed in a pantaloon cast for a two- to four-week trial period. Significant pain relief occurred in 31 (69%) of these patients. Of these 31, 23 patients were treated with spinal arthrodesis using lateral, intertransverse process fusions with iliac bone grafts. Before fusion, the painful lumbar segments were determined by facet analgesic blocks or the normal saline acceptance test. After an average follow-up period of 14 months, 17 (74%) had significant pain relief. The pantaloon cast may be an effective tool for identifying those chronic LBP patients who might benefit from spinal stabilization procedure. PMID- 8458129 TI - Analysis of Bankart lesion in the recurrent dislocation or subluxation of the shoulder. AB - The Bankart repair was used to restore anterior stability to 50 patients (51 shoulders) with recurrent dislocation or subluxation of the shoulder. The patients had preoperative diagnostic testing to determine the presence and extent of a Bankart lesion. At surgery, the Bankart lesion was carefully observed for its location, and extent of involvement of associated structures. The intraoperative findings of the severity of the Bankart lesion were compared with the preoperative data. The glenoidal fossa was considered like a clock, and the location and severity of the Bankart lesion was expressed by the hour of the clock. The Bankart lesion most frequently occurred from two o'clock to six o'clock in the right shoulder, and from six o'clock to ten o'clock in the left shoulder. The region of the glenohumeral joint at highest risk of exhibiting pathology after recurrent dislocation or subluxation of the shoulder was usually located from the central anterior edge of the glenohumeral joint to the inferior margin. Arthrogram with computed tomography was the most useful preoperative diagnostic test to demonstrate the Bankart lesion. The greatest number of inferior postoperative results were observed in patients with Bankart lesions of large size. PMID- 8458130 TI - The effect of surgical decompression on neurologic outcome after lumbar fractures. AB - From 1980 until 1989, 69 patients with lumbar fractures resulting in incomplete paraparesis were admitted to the authors' medical center for treatment. Thirty had anterior vertebrectomy, including 18 who had posterior instrumentation and four who had anterior instrumentation. Twenty-two patients were treated with a posterolateral decompression and fusion, including four who also required an anterior decompression. Nineteen of the remaining 21 patients required posterior spine instrumentation and fusion only. The American Spinal Injury Association (ASIA) motor index score was determined for each patient pre- and postoperatively and used to compare these three treatment groups. Average follow-up period for the patients was 19 months. The improvement in ASIA motor score for all patients treated with decompression averaged 10 and similar improvement was obtained in those who were treated with posterior decompression (10.2 points). The average improvement in those who had vertebrectomy was 9.9 points. For those who had fusion without decompression, average improvement was 4.2 points. Comparing those patients who were surgically decompressed, either anteriorly or posteriorly, with those patients who only underwent fusion, the difference in neurologic improvement was statistically significant. Neurologic outcome after lumbar fractures is improved by surgical decompression. The neurologic outcome results were similar after anterior and posterior decompression. PMID- 8458131 TI - Shoulder strength with rotator cuff tears. Pre- and postoperative analysis. AB - Twenty-five patients with rotator cuff tears had bilateral isokinetic shoulder strength evaluations after a pain-relieving subacromial lidocaine injection. Shoulder strength testing was repeated at six months and again at 12 months after rotator cuff surgery. Strength was recorded as a ratio of peak torques comparing the operative with the nonoperative shoulder. Preoperative strength averaged 37%, 36%, and 33% for abduction, external rotation, and forward flexion. Six-month postoperative strength increased to 68%, 76%, and 66% for abduction, external rotation, and forward flexion, respectively. Twelve-month postoperative strength increased to 104%, 142%, and 97% for abduction, external rotation, and forward flexion. Shoulders with rotator cuff tears demonstrate major objective signs of weakness. Shoulder pain obscures objective evaluation of weakness. Preoperative strength can be accurately measured after subacromial lidocaine injection. Shoulder strength is significantly improved by rotator cuff repair. PMID- 8458132 TI - A kinematic and electromyographic study of shoulder rehabilitation exercises. AB - The role of shoulder muscles during passive, active, and resistive phases of shoulder rehabilitation exercises was investigated in ten normal subjects with no history of shoulder pathology. Using the scapular plane as a reference, three dimensional motion of the shoulder was recorded with a computer-aided motion analysis system (VICON) to determine total shoulder elevation. Simultaneously, electromyographic data were acquired on nine shoulder muscles while performing the three phases of shoulder rehabilitation exercises as described by Neer. Fine wire intramuscular electrodes were placed in the following muscles: trapezius, serratus anterior, deltoid (anterior, middle, and posterior separately), supraspinatus, infraspinatus, biceps, and latissimus dorsi. Phase I (passive) exercises performed in the supine position showed the least electromyography (EMG) activity. There was a gradation of EMG activity as one progressed from Phase I (passive) to Phase II (active) to Phase III (resistive) shoulder exercises. Isometric exercises and Phase III resistive exercises showed high levels of activity in the rotator cuff and deltoid muscles. Supine Phase I exercises should be considered in the early postoperative period after shoulder surgery to achieve maximum motion while minimizing shoulder muscle activity. Progression to Phase II and Phase III exercises may proceed as soft tissue and bony healing permit. Phase III exercises performed with an elastic band should provide a satisfactory method to strengthen these muscles. PMID- 8458133 TI - Subacromial/subdeltoid bursa abscesses. An overlooked diagnosis. AB - Four subacromial/subdeltoid bursa abscesses were treated in four patients with systemic illnesses. The symptoms and signs of abscesses were minimal in all four patients. In three patients who were chronically ill and debilitated, diagnosis was established only after subacromial space abscesses were encountered during incision and drainage of the glenohumeral or acromioclavicular joint. In these three patients, the subacromial bursa abscesses coexisted with clinically diagnosed mild or resolving shoulder pyarthrosis. All had intact rotator cuffs. The subacromial/subdeltoid space should be evaluated in all cases of suspected glenohumeral pyarthrosis. Computed tomography or magnetic resonance imaging may help detect abscesses and indicate surgical therapy. PMID- 8458134 TI - Patellofemoral problems after intraarticular anterior cruciate ligament reconstruction. AB - A series of 226 anterior cruciate ligament (ACL) reconstructions were reviewed to determine the incidence of patellofemoral (PF) problems and the associated prognostic factors. Patients were divided into four groups according to the type of injury (acute or chronic) and operation (through an arthrotomy or arthroscopic assisted). The average follow-up period was 39 months. Overall there was a 5% incidence of PF crepitus with pain and/or swelling, and a further 20% of clear PF crepitus without pain. The change from open surgery and cast to arthroscopic surgery and early motion allowed a decrease of PF problems from 40% to 21% in acute injuries, but the difference was less marked in chronic knees. A deficit greater than 10% at the one-leg hop test was present in 75% of the knees with PF crepitus and pain. The height of the patella was increased in 5% and decreased in 17% of the knees. Patients with rehabilitation difficulties had the largest decrease in patella height, whereas a patella alta was more frequent after patellar tendon reconstruction. A significant correlation was found between PF problems and female gender, positive congruence angle, preoperative PF crepitation, rehabilitation difficulties, flexion loss greater than 10 degrees, extension loss greater than 5 degrees, and variation in the height of the patella. The importance of avoiding immobilization, rehabilitation difficulties, and permanent flexion or extension loss is emphasized. PMID- 8458135 TI - The relationship between proximal femoral anatomy and osteoarthrosis of the hip. AB - Proximal femoral anatomy in the anteroposterior plane was assessed by analysis of roentgenograms and the relationship between the anatomy and the pattern of osteoarthrosis of the hip was explored. The neck-shaft angle, the height of the femoral head, and the offset of the femoral head were analyzed and the type of osteoarthrosis classified according to Cameron and McNab. There was a significantly greater neck-shaft angle and a greater head height in the upward and outward migratory group. Patients being treated with total hip arthroplasty who exhibit certain types of proximal femoral anatomy might be expected to have increased acetabular loading and thus greater acetabular and femoral head wear. These data may have significance in the design of femoral components and the choice of implants in patients being treated with hip arthroplasty. PMID- 8458136 TI - Complications of trochanteric osteotomy. Long-term implications. AB - Cemented total hip arthroplasties (THAs) were performed through a Charnley transtrochanteric approach in 1162 patients from 1970 through 1986. Trochanteric separations numbered 58 (5%). Rate of nonunion was related to gender, preoperative diagnosis, and prior THA or endoprosthesis. Nonunion patients had lower mean Charnley pain and function mean scores than union patients at the 45- and 49-month examinations, respectively. A Trendelenberg gait was noted in 17% of nonunions compared with 6% of united patients. Revision rates were nearly three times higher in nonunion patients. These results indicate there is a quantifiable risk for a surgeon who chooses to use a trochanteric osteotomy. PMID- 8458137 TI - Low-frequency vibration emitted from unstable hip in human neonate. AB - Developmental dysplasia of the hip (DDH) continues to be an orthopedic enigma. Some authors still believe it is a purely birth phenomenon. Even with widespread birth screening, however, DDH continues to become evident later than three months of age, long after a satisfactory outcome can be guaranteed. In an effort to reduce the number of late manifestations, the authors have developed a noninvasive form of screening for DDH called vibration arthrometry. Five hundred neonates were examined in local maternity hospitals, according to the guidelines of Ortolani and Barlow. The new method involves the attachment of miniature accelerometers around the infant's pelvis. Using this method, it was possible to elicit vibration events from approximately one fourth (255 hips) of the hips tested; vibrations were recorded from normal hips (125), from "clicky" hips (128), and from unstable hips (two). Differences between "nil-felt" (clinically silent) and "click-felt" (palpable clicking on testing) were significant. Vibration testing can be seen as an aid in the manual palpation necessary to detect this crippling condition. PMID- 8458138 TI - Pulmonary embolism in total joint arthroplasty. AB - With a greater understanding of the prevention of thromboembolic complications, the incidence of fatal pulmonary embolism after total joint arthroplasty has declined. Although much of our knowledge is centered around deep vein thrombosis and its use as a marker for thromboembolic complications, little is known about the natural history of both symptomatic and asymptomatic pulmonary embolism. Although differing methods of prophylaxis have shown some success, the ideal agent has yet to be discovered. The use of serial lung scanning has shown great use in the diagnosis of pulmonary embolism. Additional studies using effective diagnostic tools are needed to evaluate the risk of recurrent embolism. Only then can the duration of treatment and prophylaxis be determined. Despite the many unanswered questions, the following conclusions can be drawn: (1) fatal pulmonary emboli are a preventable complication of total joint arthroplasty; (2) fatal emboli are often preceded by small and frequently asymptomatic emboli; (3) detection and appropriate therapeutic measures for asymptomatic emboli are possible with the use of serial lung scans and judicious use of pulmonary angiography; and (4) low-dose coumadin has proven to be the most effective agent in lowering the risk of asymptomatic, symptomatic, and fatal pulmonary emboli. PMID- 8458139 TI - Correction of ligament and bone defects in total arthroplasty of the severely valgus knee. AB - One hundred thirty-five knees with valgus deformity were treated with a minimally constrained, cementless total knee replacement using intramedullary alignment for the femur and tibia. Mean valgus angle before surgery was 16 degrees; mean valgus angle after surgery was 7 degrees. Neither alignment nor varus-valgus stability deteriorated during the six-year follow-up period, but the knees with greater than 25 degrees deformity had a tendency to increase posterior laxity. Severely deformed knees required bone grafting of the medial femoral and tibial surfaces. A technique was developed to resect the distal femur measured from the medial femoral condyle and to maintain joint line position. Patellar subluxation and dislocation occurred in fewer than 1% of the cases. Despite the absence of rotational constraint at the articular surface, there was no tendency for patellar stability to deteriorate over time. PMID- 8458140 TI - The electrical stimulation of tibial osteotomies. Double-blind study. AB - The effect of electromagnetic field stimulation was investigated in a group of 40 consecutive patients treated with valgus tibial osteotomy for degenerative arthrosis of the knee. All patients were operated on by the same author and followed the same postoperative program. After surgery, patients were randomly assigned to a control group (dummy stimulators) or to a stimulated one (active stimulators). Four orthopedic surgeons, unaware of the experimental conditions, were asked to evaluate the roentgenograms taken 60 days postoperatively and to rate the osteotomy healing according to four categories (the fourth category being the most advanced stage of healing). In the control group, 73.6% of the patients were included in the first and second category. In the stimulated group, 72.2% of the patients were included in the third and fourth category. On a homogeneous group of patients, electromagnetic field stimulation had positive effects on the healing of tibial osteotomies. PMID- 8458141 TI - Quadriceps force and myoelectric activity during flexed knee stance. AB - The purpose of this study was to determine the quadriceps demand during single limb stance with the knee in five positions of flexion (0 degree -60 degrees). Two variables were used to estimate the quadriceps demands: the integrated electromyogram (EMG) of three vasti and the torque about the knee joint. Ten normal subjects 23-29 years of age were tested. Myoelectric activity was recorded with intramuscular electrodes and knee joint angle with an electrogoniometer. The EMG data were integrated and normalized. A visible vector system was used to determine knee flexion torque. A significant linear correlation was found between values of patellar ligament force and knee angle (R2 = 0.86). The patellar ligament force increased 4.16% of body weight per degree of knee flexion between 0 degree and 60 degrees. Both vector-estimated quadriceps force and normalized EMG showed significant correlations with knee angle (R2 = 0.91 and R2 = 0.88, respectively). Both exhibited a slower rate of rise below 30 degrees flexion and a higher rate of rise above 30 degrees. The authors' findings suggest that the stabilizing effects of plantar flexors (except gastrocnemius) on the knee joint, changing muscle moment arm length, and force ratio between the patellar ligament and quadriceps muscle with respect to knee angle are primary reasons for the quadratic normalized integrated EMG (NIEMG)-force nonlineality during flexed stance. This might indicate the existence of a critical angle of knee flexion contracture beyond which patients cope poorly with standing and functional ambulation. PMID- 8458142 TI - Distal femoral varus osteotomy for painful genu valgum. A five-to-11-year follow up study. AB - From 1978 until 1984, 23 patients (24 knees) were treated with varus producing distal femoral osteotomy for painful, lateral compartment osteoarthrosis. Evaluation at five to 11 years (average, 8.3 years) included orthopedic examination, calculation of the Hospital for Special Surgery (HSS) knee score, and standing knee roentgenograms. Based on the objective knee scores, 71% of the patients had good or excellent results, with no difference in those followed for longer periods. Complications occurred in 63% of the cases, including nonunion (25%) and loss of correction (21%). Both complications were associated exclusively with staple fixation, which was performed during the period of this study and is now known to be inadequate to fix this osteotomy. Despite increasing morbidity rates, these complications did not appear to influence the ultimate result. A statistically significant prognostic factor was the severity of the disease as reflected by the pre- and postoperative knee scores. Further, the degree of correction was a function of the initial deformity. At follow-up evaluation 13% of the knees had been converted to a total knee replacement. PMID- 8458143 TI - Electromyographic analysis and its role in the athletic shoulder. AB - In 1944, Inman made some conclusions regarding shoulder function that have become the foundation of a classic model. Clinical observations of the athletic shoulder and its associated common injuries have demonstrated selective weakness of specific rotator cuff muscles rather than generalized muscle impairment. Shoulder mechanics during athletic activities have been evaluated dynamically with electromyography (EMG), which has helped to formulate a base for optimal rehabilitation. Dynamic EMG and high-speed film analysis have been used to evaluate the shoulder during throwing, swimming, tennis, and golf. Evaluation of shoulder function in these various sports revealed that although rotator cuff function is important in all, the emphasis and role of individual muscles varied. The importance of serratus anterior muscle activity to stabilization and protraction of the scapula has been consistently reported. The muscles about the shoulder act according to their mechanical qualities and are function- or sport specific. A thorough understanding of the mechanics of the normal and pathologic shoulder constitutes the foundation for training and rehabilitation strategies. PMID- 8458144 TI - Total knee arthroplasty using an uncemented, polyethylene tibial implant. A seven year follow-up study. AB - A seven-year postoperative evaluation of 54 patients with either osteoarthrosis or rheumatoid arthritis was conducted. Uncemented, posterior cruciate-retaining, pegged tibial implants produced clinical and roentgenographic results comparable to those seen with standard cemented total knee arthroplasty (TKA). Subsidence, however, seemed to be slightly increased in the uncemented group especially if there was incomplete coverage of the tibial plateau surface. The mere presence of subsidence was not correlated with any increase in pain, although the four implant failures in which the patients had painful loose prostheses all had some subsidence. The cumulative survival rate at seven years was 92.3%, with four arthroplasty failures. Roentgenographic appearance of condensation about the pegs was not statistically correlated with the presence or absence of pain or subsidence. The roentgenographic appearance of opacification in the declivities of the undersurface of the component, however, was associated with a statistically significant decrease in the incidence of subsidence. PMID- 8458145 TI - Salmonella typhi osteomyelitis in a nonsickle cell patient. A case report. AB - Few cases of osteomyelitis caused by Salmonella typhi in nonsickle cell patients have been reported. In a 33-year-old woman with a history of chronic, intermittent drainage of the right lower leg, roentgenographs indicated middiaphyseal osteomyelitis of the fibula. Bone cultures obtained at surgical debridement grew S. typhi. The patient responded adequately to four weeks of intravenous antibiotic therapy, and the infection has remained arrested after 18 months. The characteristics of S. typhi osteomyelitis are as follows: All reported cases have affected female patients with no apparent immunocompromise; all had a history of S. typhi infection with long bone involvement; and all had a tendency to recurrence. PMID- 8458146 TI - Nocardia septic arthritis of the hip with associated avascular necrosis. A case report. AB - Nocardiosis is a rare infection seen most commonly in immunocompromised patients. Most have pulmonary involvement, but some develop disseminated infection. There are few case reports of septic arthritis attributable to hematogenous nocardiosis. In this case, a heart transplant patient was ultimately proven to have a Nocardia septic hip but represented a diagnostic challenge because of preexisting avascular necrosis. With the increasing number of allograft recipients and concomitant immunosuppression, the possibility of an increase in Nocardia opportunistic infections exists. Avascular necrosis, attributable to corticosteroid use, may predispose patients to hip joint infection. PMID- 8458147 TI - Comparison of tissue reaction with chondroitinase ABC and chymopapain in rabbits as the basis of clinical application in chemonucleolysis. AB - Although chemonucleolysis with chymopapain is an approved treatment for lumbar intervertebral disk herniation, recent serious complications have raised doubt concerning its safety. It is therefore necessary to search for a safer and more selective agent than chymopapain for chemonucleolysis. Experimental chemonucleolysis with chondroitinase ABC was thus tested and compared with chymopapain. Acute tissue reactions to chondroitinase ABC were investigated and compared with chymopapain. The epidural space, yellow ligament, sciatic nerve, knee joint, and Achilles tendon were examined. Chymopapain damaged nervous and ligamentous tissues as well as cartilaginous tissue. Chondroitinase ABC did not damage nervous and ligamentous tissue. Chondroitinase ABC affected only cartilaginous tissue, and its action was chiefly limited to digestion of the matrix. Chondroitinase ABC has high enzymatic specificity for matrix in vivo. In addition, chondroitinase ABC is less toxic to noncartilaginous tissues than chymopapain. Chondroitinase ABC might be a more suitable and safer enzyme than chymopapain for chemonucleolysis. PMID- 8458148 TI - Human locomotion. 1966. PMID- 8458149 TI - The pathogenesis of femoral head deformity in congenital dislocation of the hip. Experimental study of the effects of articular interpositions in pigs. AB - An experimental study was conducted based on the hypothesis that articular interpositions such as inverted limbi are major factors influencing deformities of the femoral head and neck that complicate treatment of congenital dislocation of the hip. In 24 neonatal pigs, the hip was fixed in a cast for one to three hours in the frog-leg position after insertion of an allogeneic meniscus into the hip joint. No macroscopic changes were observed immediately and one day after the above procedure, but electron microscopy showed degeneration of the cells in the physis. After 29-39 days, varus deformity and flattening of the femoral head were observed in all animals. After five months, marked deformity of the femoral head and replacement of the physis by fibrous tissue were noted. Angiograms obtained during cast fixation and 30 minutes after removal of the cast showed no circulatory occlusion. A short period of immobilization in the frog-leg position combined with articular interposition plays a major role in degeneration of the physis and predisposes to deformities of the femoral head and neck. PMID- 8458150 TI - Comparison of patellar resurfacing versus nonresurfacing in bilateral total knee arthroplasty. PMID- 8458151 TI - Early diagnosis and treatment of developmental patella infera syndrome. PMID- 8458152 TI - Electromyographic analysis of the anterior cruciate ligament-deficient knee. AB - The protective relationship of the human anterior cruciate ligament (ACL) by active contraction of the hamstring musculature has been known and understood by sports orthopedists and physical therapists for many years. Rehabilitation programs for patients with torn ACLs as well as those treated with ligament reconstruction have always stressed hamstring strengthening. Research in this area during the past decade has begun to define the proprioceptive mechanism that governs this relationship as well as the actual recording of dynamic muscle firing patterns in pre- and postoperative subjects. Laboratory studies suggest that altered hamstring activity may help these subjects compensate for a knee that is lax because of ACL damage. PMID- 8458153 TI - Functional testing in the anterior cruciate ligament-deficient knee. AB - Functional testing of patients with anterior cruciate ligament (ACL) deficient knees and normal subjects during stressful activities such as running to a cut and running to a stop and during activities common to daily life, such as walking, stair climbing, and jogging, is presented. Analysis focused on the application of these tests to treatment planning and clinical evaluation. Functional testing during stressful activities indicates that some patients with ACL-deficient knees have higher than normal net hamstring moments during the early phase of these activities. These results suggest dynamic muscular substitution using the hamstrings in patients with chronic ACL-deficient knees. Patients tested during less stressful activities, such as walking and stair climbing, also demonstrated substantial differences from ACL-intact subjects. The majority of patients tended to reduce the net quadriceps moment when the knee was near full extension. Approximately 75% of the patients who were ACL-deficient developed this type of adaptation, which appears to be a subconscious method of avoiding the net anterior pull of the quadriceps mechanism when the knee is near full extension. Functional testing of the ACL-deficient knee provides meaningful information that cannot be obtained by simpler clinical tests. This information can be extremely useful in the selection and evaluation of patients with certain treatment modalities, since it seems to be directly related to some patients' ability to functionally adapt to the loss of the ACL. PMID- 8458154 TI - The normal shoulder during the butterfly swim stroke. An electromyographic and cinematographic analysis of twelve muscles. AB - This study describes shoulder muscle activity during the butterfly stroke. Upon hand entry, the deltoids and rotator cuff muscles demonstrated activity as the humerus was abducted, extended, and externally rotated. The rhomboids and upper trapezius were also active, retracting and upwardly rotating the scapula, which positioned the glenoid for the humerus. During propulsion, the pectoralis major and latissimus dorsi generated power. The subscapularis and teres minor were active to control humeral rotation. The serratus anterior helped to pull the body over the arm by reversing its origin and insertion. The posterior deltoid completed humeral extension at the end of propulsion and began to lift the arm out of the water. Then, the middle and anterior deltoids fired with the supraspinatus and infraspinatus to abduct and externally rotate the arm. The scapular muscles were also active, retracting the proximal portion of the scapula while protracting and upwardly rotating the distal tip. The glenoid then provided a platform for the humerus. Overall, the serratus anterior and the subscapularis maintained a high level of activation throughout the stroke; thus, these muscles were highly susceptible to fatigue and vulnerable to injury. PMID- 8458155 TI - The painful shoulder during the butterfly stroke. An electromyographic and cinematographic analysis of twelve muscles. AB - This paper compares the muscle firing patterns of 12 shoulder girdle muscles in competitive butterfly swimmers with painful and normal shoulders. Seven of the 12 muscles revealed statistically significant differences between the two populations. The posterior deltoid demonstrated more activity in the painful shoulders during hand entry while the upper trapezius and serratus anterior exhibited less activity. This alteration in muscle firing patterns allowed for the humerus to be positioned for a wider hand entry, which decreased the pain of impingement of the supraspinatus on the coracoacromial arch. Correspondingly, there was significantly less activity in the supraspinatus. The teres minor and serratus anterior revealed significantly less muscle action throughout pulling as they respectively failed to balance the humeral rotation and did not reverse their origins and insertions to pull the body over the arm. Also, the subscapularis and infraspinatus displayed increased activity in the painful shoulders as they depressed the humeral head to avoid impingement. There were no significant differences between the two groups in the rhomboids, pectoralis major, latissimus dorsi, or the anterior and middle deltoids. From this information, accurate preventative and rehabilitative exercise programs for the competitive butterfly swimmer can be developed. PMID- 8458156 TI - Functional recovery of noncemented total hip arthroplasty. AB - Eighteen patients with unilateral hip disease had noncemented total hip arthroplasty. Clinical follow-up data were complete to five years postsurgery. Gait analysis was done preoperatively, at three and six months, and at one and two years. Force plate data showed continued weakness of the operated hip in all patients at two years postsurgery. Preoperative dynamic electromyograms (EMGs) were abnormal in eight patients and showed two patterns. Stance loss seen in three patients was characterized by absence of activity of the gluteus medius and upper and lower gluteus maximus muscles. In five patients, continuous activity occurred in the tensor fascia lata, rectus femoris, and adductor longus muscles during the entire gait cycle. Postoperatively, all abnormal EMGs returned to normal. Four patients with a normal preoperative EMG developed abnormal EMG patterns postoperatively, demonstrating either a prolonged stance or stance loss pattern. All four of these hips have been revised. Although gait characteristics return to normal by two years postsurgery, weakness of the hip persists. This weakness jeopardizes the implant fixation interface. This study supports the prohibition of activities that cause high impact loading of total hip arthroplasties and suggests that a prolonged exercise program be employed postoperatively. PMID- 8458157 TI - Pathokinesiology and total joint arthroplasty. AB - Gait analysis data relating to total joint arthroplasty were reviewed to assess their impact on the evolution of prosthetic design. Although joint replacement designs have led to clinical improvement, they do not yet permit the restoration of normal gait. Normal function may be difficult to attain in patients with arthritic destruction, because of a proprioceptive defect. Arthroplasty improves gait by relieving pain, but other factors (previous gait patterns, prosthetic design, muscle weakness, balance, and proprioception) seem to prevent most patients from regaining normal gait. PMID- 8458158 TI - Gait performance after spinal cord injury. AB - Physiologic and mechanical gait parameters were measured in 36 spinal cord injury (SCI) patients to quantify gait impairment. Average age of the 30 males and six females was 29.0 +/- 10.1 years. Patients were tested at the time of discharge from initial rehabilitation (mean, 0.5 +/- 0.7 years postinjury). Compared with able-bodied subjects tested in the same laboratory, the SCI patients walked 52% slower (41.1 m/minute versus 79.8 m/minute, respectively), the rate of oxygen consumption was 23% higher (14.9 ml/kg.minute versus 12.1 ml/kg.minute), and the oxygen cost per meter was 240% higher (0.52 ml/kg.m versus 0.15 ml/kg.m). Peak axial load on upper extremity walking aids averaged 21.7% of body weight, and the ambulatory motor index (AMI), derived from lower limb strength grades, was 52% of normal strength. The AMI closely correlated with the peak axial load and the percent increase in the oxygen rate above normal. Differences in the AMI among patients accounted for changes in physiologic parameters; therefore, the AMI can be used as a clinical predictor of functional mobility. Annual follow-up studies were performed on ten of the 36 patients. Compared with the initial testing, these patients walked faster (59.9 m/minute versus 40.4 m/minute), more efficiently (0.26 ml/kg.m versus 0.40 ml/kg.m), with slower heart rates (115 beats/minute versus 133 beats/minute), and the peak axial load was less (18% of body weight versus 26% of body weight). PMID- 8458159 TI - Training for an academic career in neonatal medicine. AB - The rapid evolution of the subspecialty of neonatology, biologic sciences, and health care delivery provide a myriad of career opportunities. The expected complexity of a academic career in neonatal medicine in the 21st century will require training in patient care, basic and clinical sciences, and teaching and an understanding of local and national issues that have impact on care of newborns. The training of skilled neonatal health care workers and health of our infants will depend on the preparation of neonatologists who will provide clinical care and training and generate new knowledge related to the care of newborn infants and their families. PMID- 8458160 TI - A review of risk scoring for preterm birth. AB - Risk scoring is a quantitative method used to screen populations to identify persons at increased risk of developing a specific adverse health outcome. Risk scoring for preterm birth has taken the form of a simple additive score with risk factors based on clinical experience to sophisticated multivariable risk models using a large number of factors from several domains. It appears that our attempts at defining an effective risk scoring method for preterm birth have been unsuccessful. The positive predictive values (the percent of women defined as high risk that actually go on to have a preterm birth) have been relatively low (20% to 30%) and vary depending on the population studied. Several difficulties with risk scoring for preterm birth are identified. The biggest limitation of current efforts at screening for preterm birth is our ignorance of the causes of preterm birth. The role of recently defined risk factors, of the potential for synergistic relationship between risk factors, and of physician or hospital factors needs to be evaluated. Epidemiologic evidence is suggestive that preterm birth can be subclassified into preterm labor, preterm rupture of the membranes, and medically induced preterm births; however, substantial problems with misclassification, detection bias, and questionable biologic feasibility argue that these subgroups need to be validated before they can be used with confidence. Careful attention should also be paid to the statistical and methodologic limitations of risk scoring. Unless a single risk factor for a disease outcome has a relative risk over 5 and is very prevalent in the population (more than 25%), most of the disease cases will not have the risk factor. It may be unrealistic, however, to think that a single risk factor will adequately define women at high risk for preterm birth. Therefore in the future, if several lesser risk factors can be identified, multivariate modeling may prove useful in defining a valid high-risk group. In addition, attention should be paid to ensure that the risk factor assessment tools obtain accurate information and are easily reproducible among different health care providers. The reduction of preterm birth in France that occurred over a decade was accompanied by radical social changes in the ways in which the population and government perceived pregnancy and childbirth. In addition to universal access to prenatal care, population-based social changes to liberalize pregnancy leave policies and a commitment to supporting women during pregnancy were the focus of the government's commitment to reducing preterm birth.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8458161 TI - Persistent pulmonary hypertension of the newborn. The black box revisited. AB - Our understanding and therapy of PPHN, as in many other aspects of neonatology, have been clouded by our understandable fear for our patients and our wish to provide excellent care. We can no longer accept therapies that are well intentioned but unstudied. It is time that thoughtful, well-designed studies be conducted to lead us into the next century. The controversies surrounding treatment can be answered in multicentered trials. We must accept this challenge. PMID- 8458162 TI - Hypoplastic left-heart syndrome Norwood operation, transplantation, or compassionate care. AB - In our current practice, either the Norwood operation or heart transplantation must be considered reasonable options for neonates born with hypoplastic left heart syndrome. Clearly some children with this otherwise lethal defect have been helped by both approaches. Is it yet, in 1993, appropriate to delete compassionate care from our group of options? Despite all the advances of the past decade, we are not at the point where we can declare hypoplastic left-heart syndrome "cured" even for the survivors of the Norwood operation or heart transplantation. Compassionate care (including withdrawal of prostaglandin E1) is still appropriate for those families who feel that the chance of success and the quality of life are not great enough to justify the challenges the infants and their families must face. Clearly as technical modifications are made in the Norwood operation and as advances are made in transplantation biology, the number of families who choose compassionate care will decrease. PMID- 8458163 TI - Somatic gene therapy into hematopoietic cells. Current status and future implications. AB - Retroviral-mediated gene transfer is a powerful tool for introducing and expressing single genes into hematopoietic cells. There has clearly been a tremendous amount of progress in the development of retroviral gene transfer technology over the past 7 years. This is evidenced by improvements in transduction efficiency and expression in animals and its selected use currently in human trials. Critical experiments that must yet be performed relate to the in vitro identification, transduction, and expansion of pluripotent hematopoietic stem cells in vitro as well as the development of retroviral vectors that maximize in vivo expression in the desired target cells. PMID- 8458164 TI - Erythropoietin therapy for anemia of prematurity. AB - Recombinant human erythropoietin administration may prove to be a valuable adjunct in the treatment of the anemia of prematurity. This report provides an overview of fetal and neonatal erythropoiesis, the biology of erythropoietin, and the pathophysiology of the anemia of prematurity. The clinical trials using recombinant human erythropoietin in the treatment of anemia of prematurity are reviewed. Important considerations of this therapy are discussed. PMID- 8458165 TI - Feeding the low birth weight infant. AB - A true gold standard for assessing the nutritional outcome of preterm infants remains elusive. We are seeing an expansion beyond the traditional intrauterine based short-term growth and nutrient retention rates toward a broader, and possibly life-long, range of outcomes. As our nutritional end points shift, the suitability of the preterm infants' own mothers' milk may become more apparent. Whether the unique properties of human milk or the use of human milk components for fortification are sufficient to rekindle the use of donor milk from milk banks remains to be seen. Improved formulas designed specifically for preterm infants and the possibility of providing passive immunity in formula have added fuel to the debate over what constitutes an ideal nutrient source. The optimal time to begin to feed our smallest and sickest patients is being reevaluated. A policy of exclusive parenteral nutrition for prolonged periods of time may be replaced with one in which minimal amounts of feeding are used, in conjunction with parenteral support, to prepare and maintain intestinal function until advancements toward full enteral nutrition are possible. Although well-controlled trials are needed to add substance to our decisions on many feeding methods, such as intermittent bolus versus continuous gastric infusion, the use of transpyloric feeding should be discouraged. Finally, we need to determine if there are any tangible nutritional benefits from the use of nonnutritive sucking. It is hoped that resolution of some of the controversies of feeding preterm infants will broaden our clinical view of infant nutrition. The discussion on work rounds will then move away from the current "did the baby get 120 kcal/kg yesterday?" toward an informed discussion of how, what, when, and why to feed the infant. Over a century ago, Abraham Jacopi cautioned pediatricians that "You cannot feed a baby with mathematics; you must feed them with brains." PMID- 8458166 TI - Standard versus hyperimmune intravenous immunoglobulin in preventing or treating neonatal bacterial infections. AB - Although current studies suggest that IVIg is safe, larger controlled trials will soon be published and will be important to confirm this observation. In addition, the current studies do not establish the efficacy of IVIg for either treating or preventing neonatal bacterial infections. Some studies with small numbers of infants suggest benefit of IVIg therapy and prophylaxis; however, the studies reviewed do not, individually or combined, prove efficacy. Clinicians and investigators must not confuse studies that prevent infection with those that treat infection because different therapeutic regimens may be necessary. Many questions remain concerning IVIg therapy, such as is IVIg efficacious in preventing or treating neonatal sepsis, what is the appropriate immunoglobulin dosage, and how variable is the pathogen-specific antibody activity of standard IVIg products. To determine the appropriate use of IVIg in neonates effectively, well-designed and carefully controlled trials are needed to address these issues using sufficiently large numbers of infants to arrive at valid scientific conclusions. Although many questions will be answered with the trials currently in progress, we must continue to base further recommendations for immunoglobulin therapy on solid scientific data. PMID- 8458167 TI - Breastfeeding. AIDS and other infectious diseases. AB - Breastfeeding has recently been recognized as a mode of transmission of certain important pathogens. It is a major mode of transmission for CMV and HTLV-1. HIV can also be transmitted by breastfeeding, but the relative role of breastfeeding in the epidemiology of HIV is still uncertain. Breastfeeding should continue to be encouraged in the HIV-infected woman, unless safe and sufficient quantities of infant formula are available. Expressed breast milk can be contaminated with bacteria or can contain viruses shed by the donor mother. Use of expressed breast milk should be carefully controlled, with strict attention to infection control issues in obtaining, storing, and processing the milk. Physicians should be aware of the risks of transmission of viral pathogens with fresh breast milk. PMID- 8458169 TI - Has the prevalence of handicapped infants increased with improved survival of the very low birth weight infant? AB - Several methodologic issues affect the literature on the outcomes of very low birth weight children, making assessing trends difficult. A conservative estimate is that the proportion of handicapped survivors has remained stable, and with increasing survival, the absolute numbers will increase, but many studies suggest decreasing proportions with handicap. Suggestions for improving responses to the questions are proposed. PMID- 8458168 TI - Neurodevelopmental effects of cocaine. AB - How and to what extent fetal cocaine exposure produces specific, negative, long term effects on infant neurodevelopmental competence has not yet been determined. We have argued previously that results from animal studies, the findings of intrauterine growth retardation in human studies, and the markedly higher incidence of numerous associated risk factors in cocaine-exposed cohorts herald significant clinical risk to the developing infant. Recognition of infant risk status should not imply condemnation of a group of children but, as with preterm infants, lead to aggressive, national, social, and scientific efforts to delineate and intervene with potential sequelae of drug exposure. PMID- 8458170 TI - Treatment of cocaine addiction during pregnancy. AB - The treatment of cocaine abuse among pregnant women involves attention not only to the cocaine use, but also to the pregnancy and constellation of medical and social problems substance-abusing women experience. Writing about the needs of women who enter treatment for drug-dependence treatment, Reed has offered suggestions for women-oriented treatment services. Women-oriented services are those that "(1) address women's treatment needs; (2) reduce barriers to recovery, which are more likely to occur for women; (3) are delivered in a context that is compatible with women's styles and is safe from exploitation; and (4) take into account women's roles, socialization, and relative status in the larger culture." On behalf of pregnant drug-abusing women, Suffet et al argued that service delivery and treatment outcome could be enhanced by linking drug rehabilitation programs to obstetric and pediatric services. More recently, Finnegan have presented a multivariable systems approach, which includes medical and psychosocial services and Farkas et al have presented a comprehensive hospital based strategy to address perinatal addiction. Programs must address not only the drug treatment needs, but also recognize that cocaine-abusing pregnant women will soon be new mothers. It is imperative that women's programs include young children as part of the target group and integrate parent education and support to develop and strengthen women's abilities to nurture and protect children. Model programs, both residential and outpatient, that provide care and services for young children exist, but these programs are the exception rather than the rule. The intergenerational nature of substance abuse certainly argues for treatment not only for the mothers, but also for their children. PMID- 8458171 TI - Rationales for treating the human immunodeficiency virus-infected woman during pregnancy. AB - Human immunodeficiency virus (HIV) infection has become one of the leading causes of mortality among American women of childbearing age. Many women will experience a pregnancy after they have been infected. Several rationales exist for offering the pregnant infected woman anti-HIV therapy, including interruption of vertical transmission and improvement of her own health and the outcome of her pregnancy. The bases for these rationales are explored, the options (chemotherapy and immunotherapy) are described, and the potential toxicities are examined. PMID- 8458172 TI - Route of delivery of infants with congenital anomalies. AB - Obstetric delivery may be accomplished by only two methods, vaginally or abdominally. In the management of the pregnancy complicated by a fetal malformation, the choice of delivery method may be made on obstetrical grounds or in belief that one method offers the fetus benefit over the other. That choice must be based on knowledge of the nature of the individual malformation in question, the presence or absence of associated fetal malformations, the presence or absence of fetal karyotype abnormalities, fetal maturity, and fetal presentation. Clear evidence of benefit from cesarean delivery is not available in the case of many malformations that are often considered for abdominal delivery. The infrequency of many of these anomalies typically precludes the accumulation of sufficient experience in any one center or successful completion of randomized trials to evaluate treatment modalities. Most studies therefore are retrospective or flawed by small numbers of patients. Logic dictates that certain malformations that produce sufficient enlargement of fetal structures are at probable risk for dystocia of labor (e.g., severe hydrops, severe hydrocephalus, large sacrococcygeal teratoma) and may benefit from abdominal delivery. Other malformations may predispose the affected fetus to trauma or decompensation during labor and vaginal delivery. It is these anomalies that have the most controversy surrounding the "best" mode of delivery and of which we have attempted to address. Table 4 includes proposed criteria for choosing abdominal versus vaginal delivery in the gestation complicated by congenital anomaly. The birth method in the context of a fetal malformation is a choice optimally made after careful discussions with the patient, pediatrician, and pediatric surgeons. Such discussion should include a careful review of the nature of the anomaly, the optimal prognosis, and the evidence of benefit for a specific birth method. Once the pregnancy in question has been evaluated, appropriate consultations obtained, and the available data reviewed with the patient, the obstetrician again assumes a role of patient advocate. The obstetrician is the counselor, the educator, and the friend the patient needs during such a difficult time. The discussion of birth method in the case of a fetal malformation creates a conflict of interest for the patient, but typically a paradoxic result of this conflict occurs. The patient's welfare, which is usually best served by vaginal delivery, may be in conflict with the fetal concerns, which might benefit from abdominal delivery. The data might be clear but more often the data are less than convincing.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8458173 TI - Biologic basis of term and preterm labor. AB - Normal parturition in sheep and nonhuman primates appears to be initiated by signals from the fetus. These signals involve the fetal hypothalamo-hypophyseal adrenal axis and are closely integrated with the control of maturation of the fetal organs such as the lungs, gut, and kidneys that are indispensable for extrauterine life. The integrated set of changes in fetal and maternal myometrial, decidual, and cervical tissues are gradual and occur over several days. When the myometrium and cervix have been appropriately prepared, endocrine and paracrine factors in the fetal membranes, decidua, and the myometrium bring about a change in the pattern of myometrial activity from contractures to contractions. This switch occurs at night, and recurs and augments over several nights until eventually cervical dilation occurs to allow the fetus to be born. PMID- 8458175 TI - FDA issues regulations on accelerated drug-approval process. PMID- 8458174 TI - FDA clears 26 new drugs for marketing in 1992. PMID- 8458176 TI - Pharmacokinetics of oxaprozin. PMID- 8458177 TI - Relative safety and efficacy of pravastatin. PMID- 8458178 TI - Felodipine and isradipine: new calcium-channel-blocking agents for the treatment of hypertension. AB - The chemistry, pharmacology, pharmacokinetics, clinical uses, adverse effects, and dosage of felodipine and isradipine are reviewed. Felodipine and isradipine are new calcium-channel-blocking agents with FDA-approved labeling for use in the treatment of essential hypertension. Both agents are members of the dihydropyridine class of calcium antagonists, which also includes nifedipine and nicardipine. Like those agents, felodipine and isradipine affect blood pressure by producing peripheral vasodilation. Felodipine and isradipine undergo extensive first-pass metabolism; their bioavailabilities are approximately 15% and 17%, respectively. The drugs are highly protein bound but do not affect serum digoxin concentrations. Anticonvulsants may reduce the elimination half-life of felodipine. Felodipine and isradipine are effective antihypertensive agents when used alone or in combination with beta blockers or diuretics. Both agents have shown some benefit in the treatment of angina pectoris in limited studies. Clinical data do not support the use of either agent for the treatment of congestive heart failure or Raynaud's phenomenon. Felodipine and isradipine have similar adverse-effect profiles, and their adverse effects resemble those of other agents in the class. Common adverse effects are peripheral edema and increased heart rate. The initial dosage of isradipine for the treatment of hypertension is 2.5 mg twice daily. Felodipine should be started at a dosage of 5 mg once daily. Felodipine and isradipine are effective antihypertensive drugs but have not demonstrated clear advantages over other dihydropyridine calcium-channel blockers. PMID- 8458179 TI - Specialized nutritional support in respiratory disease. AB - Nutritional status in patients with respiratory disease is discussed and nutritional support and pharmacotherapy considerations in these patients are reviewed. Undernutrition is common among patients with respiratory disease and can lead to decreased respiratory muscle mass and ventilatory drive. Both overfeeding and underfeeding can adversely affect patient outcome. Specialized nutrition-support regimens for patients with respiratory disease should include carbohydrate doses below the maximal oxidative rates for glucose and fat emulsion as a daily continuous infusion. Early enteral feeding may be beneficial. Respiratory quotient, oxygen consumption, and carbon dioxide production are useful measurements in providing optimal nutrition support. Pharmacotherapeutic measures, such as gastrointestinal-tract decontamination and growth-hormone administration, are being investigated in these patients as adjunctive therapy. Nutrition-support regimens for patients with respiratory disease should be carefully designed and monitored to avoid further compromising respiratory function and to reduce the risk of infection. PMID- 8458180 TI - Bioequivalence of oral and injectable levoleucovorin and leucovorin. AB - The bioequivalence and bioavailability of oral and intravenous formulations of levoleucovorin and leucovorin were studied, and the absolute bioavailabilities of levoleucovorin and leucovorin tablet formulations were determined. Healthy male volunteers participated in two randomized, single-dose, four-way crossover studies. The treatment groups were as follows: A = five 2.5-mg levoleucovorin tablets, B = five 5-mg leucovorin tablets, C = one 12.5-mg levoleucovorin tablet, D = one 25-mg leucovorin tablet, in study 1; A = 15-mg levoleucovorin injection, B = two 7.5-mg levoleucovorin tablets, C = 30-mg leucovorin injection, D = two 15 mg leucovorin tablets, in study 2. Serum concentrations of N-5 methyltetrahydrofolate (the primary metabolite and circulating form of reduced folate after leucovorin administration) and total tetrahydrofolate were measured over 24 hours after dose administration. Pharmacokinetic values were calculated for N-5-methyltetrahydrofolate and total tetrahydrofolates; values were compared for A versus B, C versus D, A versus C, and B versus D in study 1 and A versus C and B versus D in study 2. Results from 35 men in study 1 and 33 in study 2 showed that 12.5-mg oral doses and 15-mg intravenous doses of levoleucovorin are bioequivalent to 25-mg oral doses and 30-mg intravenous doses of leucovorin, respectively. Equivalence was observed after oral and intravenous administration. The absolute bioavailability of levoleucovorin (74%) was not significantly different from that of leucovorin (65%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458181 TI - Effect of hydrochlorothiazide, enalapril, and propranolol on quality of life and cognitive and motor function in hypertensive patients. AB - The effect of hydrochlorothiazide, propranolol, and enalapril on cognitive and motor function and quality of life (QOL) in hypertensive patients was studied. Patients > or = 55 years of age with asymptomatic essential hypertension were included in a randomized, double-blind, placebo-controlled, crossover study. Subjects discontinued their previous antihypertensive agents and started hydrochlorothiazide 25 mg, extended-release propranolol hydrochloride 120 mg, enalapril maleate 10 mg, or placebo. One capsule was taken for three days and then the dosage was doubled for the remainder of a four-week period. Subsequent crossover treatments were begun without a washout period. In each treatment phase, a battery of psychometric tests was used to assess cognitive and motor function and quality of life; all tests but one were self-administered via computer terminal. Pulse rate and blood pressure were recorded, and compliance was monitored by capsule count. Sixteen of 30 patients interviewed completed the trials; one additional patient was evaluated after receiving all treatments except hydrochlorothiazide. Mean +/- S.D. age of the subjects was 66 +/- 6.1 years; 10 were black and 7 white; 9 were men. Except for the hydrochlorothiazide group, blood pressure in the active treatment groups did not differ significantly from placebo; hydrochlorothiazide significantly reduced systolic but not diastolic blood pressure compared with placebo. Compared with placebo, hydrochlorothiazide was associated with fewer incorrect responses in a test of complex reaction time and with greater discriminant reaction time response rates; otherwise, no difference between groups was noted in cognitive or motor performance. There were no significant differences between active treatments and placebo on individual QOL measures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458182 TI - Reviews of new drugs. PMID- 8458183 TI - Criteria for use of warfarin in adult inpatients and outpatients. PMID- 8458184 TI - Statistics in Diabetic Medicine: how confident can you be. PMID- 8458185 TI - Bioartificial pancreas. PMID- 8458186 TI - A prospective study of sensory function in patients with type 2 diabetes. AB - Sensory function was prospectively examined in 201 Type 2 diabetic patients over a 2-year period. Quantitative sensory testing for vibration, cool, warm, and pressure perception at the hallux was performed at baseline, 1-month, 1-year, and 2-year visits. There were statistically significant increments of thresholds for all sensory modalities from the baseline visit to the 1-year visit (p < 0.001) and from the 1-year visit to the 2-year visit (p < 0.001). Thirty percent of 77 subjects considered to be at low risk for foot ulceration at baseline progressed to a higher risk category at the 2-year visit. There were no significant differences in mean glycosylated haemoglobin, height, sex distribution, age, or diabetes duration when patients who had a faster progression of insensitivity were compared with patients who had a slower progression. There was a high degree of autocorrelation between baseline and 2-year visits for all sensory modalities (r = 0.83 to r = 0.88, p < 0.001 for all). Also, changes in sensory thresholds from the baseline to 2-year visits for one modality tended to correlate with other modalities (r = 0.36 to r = 0.70, p < 0.001 for all). These data indicate that an appreciable proportion of Type 2 diabetic patients are at risk for a marked rate of decline of sensory function, and suggest a need for at least yearly quantitative sensory testing. PMID- 8458187 TI - Overt diabetic neuropathy: repair of axo-glial dysjunction and axonal atrophy by aldose reductase inhibition and its correlation to improvement in nerve conduction velocity. AB - Clinically overt diabetic neuropathy is characterized by neuroanatomical changes of the node of Ranvier and myelinated axons, and by decreased nerve conduction velocity. Sural nerve biopsies were obtained from 16 neuropathic diabetic patients participating in a 12-month randomized, placebo-controlled, double-blind clinical trial of the aldose reductase inhibitor sorbinil. One sural nerve biopsy was obtained at baseline and a second biopsy at the termination of the trial. Ten sorbinil-treated patients showed significant improvement in axo-glial dysjunction, a characteristic lesion of the node of Ranvier. Axonal atrophy assessed by three independent morphometric techniques also exhibited significant recovery in the sorbinil-treated patients. No change was demonstrated in any of these structural parameters in six placebo-treated patients. The improvement in sural nerve conduction velocity in sorbinil-treated patients correlated with the product of the quantitative improvements in axo-glial dysjunction and axonal atrophy. We conclude that the activated polyol-pathway plays a sustaining role in nerve fibre damage in diabetic neuropathy, and that structural lesions such as axo-glial dysjunction and axonal atrophy which are reversible following intervention with an aldose reductase inhibitor, constitute the morphological basis for nerve conduction slowing in overt diabetic neuropathy. PMID- 8458188 TI - Prothrombotic and antithrombotic factors are elevated in patients with type 1 diabetes complicated by microalbuminuria. AB - Increased urinary albumin loss in patients with Type 1 diabetes is associated with accelerated atherosclerosis. Prothrombotic factors known to be associated with cerebrovascular and coronary artery disease in the general population, antithrombotic factors, were studied in 52 patients with Type 1 diabetes and varying urinary albumin loss and 24 non-diabetic control subjects. Fibrinogen increased from 2.5 g l-1 (95% confidence interval 2.3-2.8) in control subjects and 2.8 g l-1 (2.6-3.0) in diabetic patients without microalbuminuria to 3.1 g l 1 (2.7-3.5) with microalbuminuria (p < 0.005 vs control; p < 0.001 vs without microalbuminuria). Factor VIIc increased from 81% (75-86% in non-diabetic control subjects and 84% (78-90%) in diabetic patients without microalbuminuria to 103% (89-117%) with microalbuminuria (p < 0.005 vs control; p < 0.05 vs without microalbuminuria) and 118% (86-150%) with albuminuria (p < 0.005 vs control and p < 0.001 vs without microalbuminuria). Levels of the antithrombotic factors protein C, protein S, and antithrombin III also rose in the diabetic patients with evidence of renal damage. Elevation of prothrombotic factors has been associated with increased risk of microvascular disease, whereas elevation of antithrombotic factors has no known protective effect. Therefore, this pattern of alteration of haemostatic factors in diabetic renal disease may contribute to the increased risk of vascular disease associated with both microalbuminuria and albuminuria. PMID- 8458189 TI - Long-term effect of acarbose on glycaemic control in non-insulin-dependent diabetes mellitus: a placebo-controlled double-blind study. AB - The efficacy and safety of acarbose therapy (100 mg tds for 24 weeks) was investigated in a placebo-controlled double-blind study in patients with non insulin dependent diabetes mellitus who could not achieve satisfactory glycaemic control by diet alone. In the acarbose group, the 2 h postprandial blood glucose and haemoglobin A1 levels decreased significantly from 14.0 mmol l-1 to 11.3 mmol l-1 and from 11.1% to 9.7%, respectively. In the placebo group, the 2 h postprandial blood glucose (14.4 mmol l-1 to 14.2 mmol l-1) and the hemoglobin A1 level (10.3% to 9.9%) showed no significant changes. A 75 g oral glucose tolerance test was performed before and after the study, the difference not being significant in either the acarbose group or the placebo group. The incidence of side-effects (mainly gastrointestinal symptoms such as flatulence and abdominal distension) was high at 78.9% in the acarbose group and 61.1% in the placebo group. However, there was no significant difference between the groups, and side effects in the acarbose group tapered during the trial, suggesting that some at least were not related to the drug. From these findings, it was concluded that acarbose is an effective new treatment for diet treated non-insulin-dependent diabetic patients. PMID- 8458190 TI - Insulin insensitivity is associated with a decrease in postprandial thermogenesis in normal pregnancy. AB - Insulin sensitivity and postprandial thermogenesis were investigated at various stages of pregnancy to assess if changes in insulin sensitivity contribute to energy conservation during pregnancy. Cross-sectional and longitudinal studies were undertaken. Sixteen control non-pregnant women were compared with 10 women in the second trimester (2nd) and thirteen women in the third trimester (3rd) of uncomplicated pregnancy. Six women were studied at all three time points. The slope of plasma glucose decline following a bolus of intravenous insulin was used as an index of insulin sensitivity. Resting energy expenditure was measured with continuous indirect calorimetry. Postprandial thermogenesis was measured as the change in energy expenditure for the 2 h after a mixed meal. Results are expressed as mean +/- SEM or median (interquartile range). Insulin sensitivity was lower as pregnancy progressed (non-pregnant control 181 (177-205) vs 2nd 111 (100-112) vs 3rd 96 (80-109) mumol l-1 min-1, p < 0.001). Fasting insulin levels were significantly higher in the third trimester but not in the second trimester (non-pregnant control 1.9 (1.5-6.0) vs 2nd 3.1 (2.8-5.2) vs 3rd 8.6 (4.8-9.7) mU l-1, p < 0.05). Meal stimulated insulin levels were higher in the second and third trimesters compared to non-pregnant women (insulin area over 2 h, postmeal, non-pregnant control 78 +/- 10 vs 2nd 92 +/- 14 vs 3rd 145 +/- 14 mU l-1 h-1, p < 0.005). Postprandial thermogenesis was lowest in the third trimester (non pregnant control 103 +/- 5 vs 2nd 74 +/- 8 vs 3rd 48 +/- 8 kJ, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458191 TI - The relationship between obesity, plasma immunoreactive insulin concentration and blood pressure in newly diagnosed Indian type 2 diabetic patients. AB - The association of blood pressure with clinical and biochemical measures was studied in 185 newly diagnosed Type 2 diabetic patients, 74 impaired-glucose tolerant (IGT) and 128 non-diabetic control subjects. Hyperglycaemic subjects were older than control subjects (controls 40 (24-59) years, IGT 48 (29-64) years, diabetic 43 (29-60) years, median (5th-95th centile) both p < 0.05). They were also more obese (body mass index (BMI) controls 23.5 kg m-2 (17.2-29.9), IGT 26.0 kg m-2 (19.8-33.9), diabetic 24.2 kg m-2 (19.3-32.2)) and with a greater waist-hip ratio (controls 0.83 (0.70-0.98), IGT 0.88 (0.75-0.98), diabetic 0.89 (0.75-1.00)). Blood pressure was significantly higher in both IGT (systolic 127 mmHg (108-162), diastolic 84 mmHg (66-99)) and diabetic patients (systolic 130 mmHg (104-160), diastolic 84 mmHg (66-102)) compared to non-diabetic controls (systolic 120 mmHg (100-151), diastolic 80 mmHg (60-94)). Univariate analysis showed that in diabetic patients systolic blood pressure was related to age (r = 0.17, p < 0.05), BMI (r = 0.23, p < 0.01) and plasma immunoreactive insulin (fasting and post glucose, r = approximately 0.25, p < 0.01) but not to C-peptide concentrations; diastolic blood pressure to BMI (r = 0.35, p < 0.001), waist-hip ratio (r = 0.23, p < 0.01) and plasma immunoreactive insulin (fasting r = 0.30, p < 0.001, post glucose r = approximately 0.20, p < 0.05) but not to C-peptide concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458193 TI - Growth hormone levels in patients with type 1 diabetes are age related. AB - Possible effects of age on the growth hormone (GH) levels in Type 1 diabetes were examined. The study was performed in 71 patients with Type 1 diabetes (40 C peptide negative (CpN), without residual beta cell activity; 31 C-peptide positive (CpP), with preserved beta cell activity) and 11 healthy subjects. The patients and controls were divided into three age groups (A = 21-30; B = 31-40; C = 41-50 years). Blood glucose and growth hormone (GH) were measured at hourly intervals during 24 h in all subjects in hospital conditions. GH levels decreased significantly with age in patients with Type 1 diabetes (mean 24-h GH group A: 7.3 +/- 1.0, group B:5.3 +/- 0.6, group C: 3.7 +/- 0.4 mU 1(-1); A vs C: p = 0.0007; B vs C: p = 0.03). In all age groups GH levels were significantly higher in CpN than either in CpP diabetic patients or controls (group A CpN: 8.3 +/- 1.2, CpP: 4.7 +/- 1.0, controls: 2.2 +/- 0.3 mU 1(-1); p < 0.001; group B CpN: 7.3 +/- 0.8, CpP: 3.2 +/- 0.5, controls: 1.6 +/- 1.0 mU 1(-1); p < 0.0002; group C CpN: 5.2 +/- 0.5, CpP: 2.5 +/- 0.4, controls: 1.4 +/- 0.4 mU 1(-1); p < 0.001). Mean GH levels were significantly higher in C-peptide positive patients than in controls in all age groups (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458192 TI - The role of plasma non-esterified fatty acids during exercise in type 2 diabetes mellitus. AB - Elevated fasting plasma non-esterified fatty acid (NEFA) levels have been reported in Type 2 diabetes. We examined whether such changes persist during low grade exercise and influence carbohydrate metabolism. Eight Type 2 diabetic patients with moderate glycaemic control and eight healthy controls received the anti-lipolytic agent, acipimox, or placebo on separate occasions before exercising for 45 min at 35% pre-determined VO2max. Fasting plasma NEFA levels were similar (0.40 +/- 0.06 (SEM) and 0.45 +/- 0.05 mmol l-1; healthy and Type 2 diabetic subjects) following placebo, and increased to comparable levels with exercise (0.73 +/- 0.07 and 0.73 +/- 0.10 mmol l-1). Acipimox lowered basal NEFA levels (0.14 +/- 0.03 and 0.28 +/- 0.04 mmol l-1; both p < 0.05 vs placebo), and prevented the rise with exercise. Blood glucose (p < 0.001) and serum insulin (p < 0.01) levels were higher in the Type 2 diabetic patients (vs controls) for both treatments. Whole body lipid oxidation increased from baseline to a comparable degree with exercise following placebo (3.2 +/- 0.3 and 2.8 +/- 0.3 mg kg-1 min 1; healthy and Type 2 diabetic subjects, both p < 0.02). Although less marked, the same was also observed following acipimox (2.0 +/- 0.4 and 2.1 +/- 0.5 mg kg 1 min-1; both p < 0.05). Carbohydrate oxidation increased with exercise in both subject groups, but with no significant difference between the treatments. Thus, the metabolic response to low-grade exercise was normal in Type 2 diabetic patients with moderate glycaemic control, but occurred against a background of hyperinsulinaemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458194 TI - Use of fructosamine and glycated haemoglobin to verify self blood glucose monitoring data in diabetic pregnancy. AB - Relationships between fructosamine and HbA1, and mean blood glucose over the previous 1-8 weeks, determined from self blood glucose monitoring with memory meters, were studied prospectively throughout 16 pregnancies in Type 1 diabetic women. Fructosamine correlated best (Spearman rank) with mean blood glucose over the previous 2 weeks in the first and second trimesters (0.5) and over the previous 1 week in the third trimester (0.39). HbA1 correlated best with mean blood glucose over the previous 8 weeks in the first and second trimesters (0.56), but over the previous 2 weeks in the third trimester (0.524) probably because of increased erythropoiesis in late pregnancy. From Deming regression models, 95% prediction intervals for mean blood glucose for fructosamine and HbA1 values were calculated, showing that fructosamine predicted levels of mean blood glucose more precisely than HbA1. These intervals can be used to estimate an individual pregnant diabetic woman's mean blood glucose from her fructosamine or HbA1 results and to verify self blood glucose monitoring data. In well-controlled diabetic pregnancy, both fructosamine and HbA1 reliably indicated trends in blood glucose but fructosamine estimated blood glucose levels more precisely. PMID- 8458195 TI - A model for early diagnosis of type 2 diabetes mellitus in primary health care. AB - The aim of the study was to determine the feasibility of conducting a case finding programme for Type 2 diabetes mellitus in primary health care and to see whether random urinary glucose or random capillary blood glucose testing is the most suitable instrument for the early detection of Type 2 diabetes. Residents in the community of Laxa aged 35-64 years were subjected to testing during 1983 1987; those aged 65-79 were included from July 1985 and onwards. The urinary glucose testing was considered positive if a urinary dipstick was not unequivocally negative. The random blood glucose test was regarded as positive when > or = 8.0 mmol l-1. A diagnosis of Type 2 diabetes made within a follow-up period of 3 years from the initial examination was regarded as a positive outcome. Random blood glucose testing was performed on 3268 persons which was close to 85% of the eligible population. Urinary glucose tests were missing in 67 subjects. The random blood glucose test was positive in 220 persons and the urinalysis in 42 persons. A total of 234 individuals had a positive test, out of which 66 new diabetic cases were found. Sixty-four of these were detected by the random blood glucose testing and 20 by the urinalysis. The sensitivity for the random blood glucose and urinary glucose testing was 73 and 23%, the specificity was 95 and 99%, the positive predictive value 29 and 48%, and the negative predictive value 99 and 98%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458197 TI - Diabetes education: an Asian perspective. AB - Asian diabetic patients often lack knowledge about diabetes and self-management of the disease due to difficulties in communication. The introduction of a diabetes education programme specifically for Asian patients has resolved many of the communication problems, provided education which Asian patients could understand, and raised awareness of diabetes within the Asian community. Forty eight percent of Asian patients were unable to read, while only 26% spoke and 20% read English, emphasizing the need for education in Asian languages using oral and visual teaching methods. Cultural differences were identified such as the use of alternative therapy to supplement treatment (33%) and the large number of vegetarians (61%). Public awareness of diabetes in the Asian community was increased by providing health education at social venues. The provision of diabetes education designed for the needs of Asian patients is essential to improve the quality of life and life expectancy of these patients. PMID- 8458196 TI - Long-term use of intramuscular insulin therapy in a type I diabetic patient with subcutaneous insulin resistance. AB - We studied a 26-year-old Type 1 diabetic patient who experienced recurrent episodes of ketoacidosis and who was unresponsive to subcutaneous insulin, but normally responsive to intravenous insulin as demonstrated by insulin challenge test. Attempts at intravenous and intraperitoneal insulin administration were complicated by recurrent septicaemia. We therefore investigated the hypoglycaemic effect of intramuscular insulin administration in this patient. After intramuscular injection of NPH and Ultralente human insulin (0.1 U kg-1), the lowest plasma glucose levels occurred 1 and 7 h later, respectively; the hypoglycaemic effect lasted approximately 2 and 12 h, respectively. We based insulin therapy on intramuscular NPH as a fast-acting insulin and Ultralente as an intermediate-acting insulin using four injections a day. During the next 24 months, the patient was hospitalized for 4 weeks versus 56 weeks in the 20 months preceding intramuscular insulin administration, and was able to resume full-time work. HbAlC decreased from 11.7% to 8.7% (normal range: 4.2-5.9%). Thus, long term intramuscular insulin therapy is a feasible alternative to intravenous or intraperitoneal insulin in patients with well-demonstrated resistance to subcutaneous insulin. PMID- 8458198 TI - Hypoglycaemic admissions among diabetic patients in Soweto, South Africa. AB - An audit of hypoglycaemic admissions among diabetic patients to Baragwanath Hospital, Soweto, South Africa was carried out prospectively during a recent 5 month period. A total of 51 episodes of biochemically confirmed hypoglycaemia (blood glucose < 2.2 mmol l-1 with coma or pre-coma, and requiring intravenous glucose) were observed in 43 patients. There was a wide range of ages (22-88 years) and an excess of males (27 M:16 F). Fourteen (33%) cases were associated with sulphonylurea (gliclazide) treatment. Doses of insulin or sulphonylureas were not excessive. The major cause precipitating the event was a missed meal (36%), though alcohol (22%), gastrointestinal upset (20%), and inappropriate treatment (18%) were also important contributory factors. Following recovery from the event, doses of drugs or insulin were frequently reduced, and three patients were successfully taken off insulin, and six off gliclazide. There was no mortality in this series, and no obvious long-term morbidity. We conclude that severe hypoglycaemia is a frequent and important acute diabetic complication in Soweto. Patient education and care in prescribing for Type 2 diabetic patients may help reduce its occurrence and severity. PMID- 8458199 TI - Use of insulin for 50 years or more in North Canterbury, New Zealand. AB - Previous reviews of diabetic subjects using insulin for 50 years or more have been based on clinic populations or on individuals receiving medals to mark this achievement. We interviewed all 11 subjects who had been on insulin for 50 years or more, identified from a population-based register of insulin users in North Canterbury, New Zealand. Seven of the 11 subjects had required treatment for micro- or macrovascular disease, but the functional level of the majority of survivors was nevertheless high. Diabetes had a major social impact on only one of the subjects interviewed. PMID- 8458200 TI - IDDM in sub-Saharan Africa. PMID- 8458201 TI - Prevalence and sources of occupational contact sensitization to acrylates in Italy. AB - Acrylate-based products are widely utilized in the industrialized world and in the domestic environment. The aim of this study was to evaluate the prevalence and sources of occupational contact sensitization to acrylates in a selected population. Between January 1987 and April 1992, 82 patients suspected of occupational acrylic sensitization were patch tested with the GIRDCA standard series and an extensive acrylate series. Over this 5-year period, we detected sensitization to acrylates in 13.4% of cases. Dental materials and anaerobic sealants were the most important sources of acrylate sensitization. Among acrylic monomers, ethylene glycol dimethacrylate was the most frequent contact sensitizer in our study. Acrylate additives were also important sources of contact dermatitis in our patients. Although the clinical picture of airborne contact dermatitis due to acrylates has rarely been reported in the literature, it was commonly observed in our patients. PMID- 8458202 TI - Electrical impedance index in human skin: measurements after occlusion, in 5 anatomical regions and in mild irritant contact dermatitis. AB - The electrical impedance in 23 healthy volunteers at 2-6 different skin sites was measured with a new impedance device, which makes possible non-invasive local measurements to a controlled depth. In 11 subjects, the test sites were occluded for 24 h using empty Finn Chambers and chambers with water, physiological saline, a paper disc or 0.002% sodium lauryl sulfate (SLS). In the normal skin of 10 subjects, the electrical impedance was measured from 5 different body areas for 5 consecutive days. In 3 subjects, daily measurements for 1 month were done, both from normal skin and from skin following the application of 2% SLS. The results show that the irritation index based on electrical skin impedance gives little day-to-day variation at one and the same test site, in comparison to the variations between different test sites on the same subject and the interindividual variations observed. Significant differences in impedance values between different anatomical regions of normal skin were found. Occlusion does not affect readings taken 24 h or later after removal, but increases variance for readings taken 1 h after removal. Effects on the skin of mild irritation and its recovery phase are easily monitored with the new device. Technology based on electrical impedance, in its newly presented form, with the advantages of improved geometrical definition and depth control, can be used as an objective tool to measure skin irritation. For detection of subclinical irritant contact dermatitis, repeated readings taken over several days may be needed. PMID- 8458203 TI - Contact dermatitis from feprazone. PMID- 8458205 TI - Allergic contact dermatitis from benzydamine with probable cross-reaction to indomethacin. PMID- 8458204 TI - Systemic contact dermatitis from isoniazid. PMID- 8458206 TI - Further epidemiologic study of occupational contact dermatitis in the dental clinic. PMID- 8458208 TI - Occupational contact dermatitis from Kathon 930. PMID- 8458207 TI - Allergic contact dermatitis from budesonide. PMID- 8458209 TI - Allergic contact dermatitis from cetyl pyridinium chloride in latex gloves. PMID- 8458210 TI - Urticaria and angioedema during insemination with fluid containing bovine serum albumin. PMID- 8458211 TI - Hand dermatitis in a hand cleanser salesman. PMID- 8458212 TI - Allergic contact dermatitis from adhesive plaster due to colophony and epoxy resin. PMID- 8458213 TI - Generalized eczematous reaction to erythropoietin. PMID- 8458214 TI - Contact dermatitis from epsilon-aminocaproic acid. PMID- 8458215 TI - Contact sensitivity to sorbic acid. PMID- 8458216 TI - Allergic contact dermatitis of the genitals from rubber additives in condoms. PMID- 8458217 TI - Contact allergy to benzalkonium chloride and glutaraldehyde in a dental nurse. PMID- 8458218 TI - Contact dermatitis among decorators and enamellers in hand-made ceramic decorations. PMID- 8458219 TI - Contact dermatitis and contact sensitization among enamellers and decorators in the ceramics industry. AB - 126 enamellers and 64 decorators from 5 factories underwent dermatological and allergological examination using occupational test series in order to evaluate the prevalence of dermatitis and contact sensitization, and to identify the most important sensitizing substances. 48 workers (corresponding to 25.26% of the study population) were sensitized, with a total of 55 positive patch tests. Dermatitis was present in 22 workers, whereas 44 subjects claimed to have had skin lesions in the past. We found 17 positivities to specific substances: 7 to red iron oxide; 2 to antimony trioxide, manganese dioxide and maleic anhydride; and 1 to red copper oxide, cadmium chloride, vanadium pentoxide and sodium tripolyphosphate. PMID- 8458220 TI - Release of thiurams and carbamates from rubber gloves. AB - A method for quantitative determination of thiuram and carbamate derivatives released from rubber gloves into synthetic sweat is presented. The analysis was based upon determination of ester derivatives using gas-chromatography/mass spectrometry and isotope-dilution. The detection limit was 0.1 mg thiuram/carbamate in 200 ml synthetic sweat (0.5 ppm). The release of thiurams and carbamates from 5 household and 5 surgical types of gloves into synthetic sweat was determined. Each of the natural rubber gloves released varying amounts of thiurams (0-4.3 mg) as well as carbamates (0-8.1 mg). 22 thiuram-sensitized patients were patch tested with pieces of the gloves. Gloves releasing considerable amounts of thiurams and/or carbamates seemed to cause more positive patch test reactions in these patients than gloves releasing smaller amounts. Surgical gloves made from natural rubber caused a substantial larger number of positive patch test reactions than household gloves made from natural rubber. The amounts released per cm2 of the gloves were of the same order of magnitude as the content per cm2 patch test of thiuram mix, diluted 1:10. The accessibility of a quantitative, chemical analysis for thiurams and carbamates released from rubber gloves makes it reasonable to ask for declarations of rubber gloves. Proposals for threshold values for release of thiurams and carbamates from rubber gloves may be given in the future. PMID- 8458221 TI - An investigation of the allergenic constituents of Cladonia stellaris (Opiz) Pous & Vezda ('silver moss', 'reindeer moss' or 'reindeer lichen'). AB - The sensitizing potency of Cladonia stellaris ('reindeer lichen', 'silver moss') extracts was determined in guinea pigs by a modified FCA (Freund's complete adjuvant) test. The lichen showed a moderate sensitizing potency. Similar investigations with pure common lichen constituents revealed a moderate sensitizing potency for fumarprotocetraric acid and atranorin and a weak one for evernic acid, stictic acid and both forms of usnic acid. Although generally weak, (-)-usnic acid was at least 2 x stronger than (+)-usnic acid. After separation of the Cladonia ether extract into 'usnic-acid-free' and 'usnic-acid-containing' fractions, perlatolic acid was identified as the main allergenic constituent of the 'usnic-acid-free' fraction. Stictic, evernic, fumarprotocetraric acid and atranorin were not detectable. Lichens and lichen products generally possess a weak to moderate sensitizing capacity. Compared with common sensitizers of occupational and environmental importance, these products play only a minor role. PMID- 8458222 TI - Allergic contact reaction to dexpanthenol: lymphocyte transformation test and evidence for microsomal-dependent metabolism of the allergen. AB - In a patient with contact dermatitis, dexpanthenol was found to be the causative allergen. There was a positive reaction to dexpanthenol on patch testing. Controls did not show any positive reactions to dexpanthenol on patch testing. Additionally, an LTT was performed. After preincubation with dexpanthenol modified microsomes, we observed an increase in lymphocyte proliferation to dexpanthenol, in comparison to dexpanthenol without microsomes, suggesting that microsomal metabolism plays a role in the pathogenesis of dexpanthenol sensitization, because microsomes are known to possess drug metabolizing enzymes such as cytochrome P450. PMID- 8458223 TI - An arm immersion model of compromised skin (I). Influence on irritation reactions. AB - Patch testing and safety evaluation processes to assess the allergic or irritant potential of substances are usually performed on normal skin. However, the reactivity of compromised skin may be different. Consequently, it is important to have a test procedure which acts as a model for compromised skin and which reproduces on the target sites the cumulative insult which results from repeated exposure, working temperatures, hydration and the action of surfactants. The procedure described uses regular immersion of forearm skin in an aqueous solution of sodium dodecyl sulphate until an identifiable alteration of skin condition is produced. In this first report, the model system has been described in detail and the influence of skin compromise on the response to 3 irritants, citral, sodium dodecyl sulphate and nonanoic acid, has been assessed. The irritation potential of the materials varied, but each irritant produced a greater degree of reaction on skin compromised to be within the normal clinical range one might expect from housework. PMID- 8458224 TI - Allergic contact dermatitis due to a Chinese orthopaedic solution tieh ta yao gin. AB - 3 cases of contact dermatitis due to a Chinese herbal orthopaedic solution Tieh Ta Yao Gin and its putative ingredients are reported. Patch testing demonstrated allergy to mastic and myrrh, natural gum resins widely used in traditional Chinese medicine to relieve pain and swelling due to traumatic injury. PMID- 8458225 TI - Contact dermatitis and its relationship to atopy in workers on the Polish State Railways. AB - Clinical examinations, patch tests and prick tests were carried out in a group of railwaymen. Only 3 had both eczema and atopy. Prick tests were positive in a high proportion of subjects, including both those with eczema and controls. PMID- 8458226 TI - N-acetylglucose aminidase activity in corneoscleral ulceration after severe eye burns. AB - In some patients with severe burns, major problems were delayed regeneration of the surface epithelium, extensive ulceration of the sclera near the limbus, subsequent corneal ulceration, and subconjunctival scarring. Human tissues surrounding ulcerations in severe eye burns were obtained from surgical interventions in 12 such patients. High activities of the lysosomal marker enzyme N-acetyl-glucose aminidase were found. As is known from histological examinations, these tissues do not represent regeneration of conjunctiva, but rather inflammatory proliferation. The tissues adjacent to corneoscleral ulceration release large amounts of lysosomal destructive enzymes. The rather simple assay of the activity of the N-acetylglucose aminidase proved useful in clinical cases to assess the activity of the inflammation of eye burns and to estimate the efficacy of the therapy applied. PMID- 8458227 TI - Effect of Pseudomonas aeruginosa concentration in experimental contact lens related microbial keratitis. AB - Pseudomonas aeruginosa adherence in vitro to perfilcon A (ionic, 71% H2O) extended wear soft contact lenses--both new and after 7 days of continuous wear on closed rabbit eyes--was found to be related directly to the bacterial concentration in the contaminating solution. Thirty rabbits wore perfilcon A lenses for 7 days with complete lid closure to mimic contact lens overwear. After 7 days, conjunctival cultures showed no growth of pathogens, but all corneas had developed epithelial cell exfoliation and/or epithelial defects and stromal edema. The lenses were then incubated in various concentrations (10(7), 10(6), 10(5), 10(4), and 10(2) colony-forming units per milliliter or saline control; n = 5/group) of P. aeruginosa suspensions and replaced on their respective corneas with tarsorrhaphies for an additional 48 h. By day 9, corneal thickness had increased significantly, and P. aeruginosa keratitis had developed in 13 of 25 bacterially exposed eyes but not in 5 control eyes. Although with decreasing P. aeruginosa concentration the prevalence of ulcerative microbial keratitis also decreased, the initial concentration of bacteria or the initial extent of soft contact lens-induced corneal damage had no influence on the ultimate clinical severity of the disease. PMID- 8458228 TI - Intraocular pressure and corneal curvature changes on application of limbal scleral suction fixation ring in rabbits. AB - Suction rings are used to stabilize the globe during refractive surgery procedures. This study investigates the changes in ocular pressure and corneal curvature induced by a suction ring on rabbit corneas. A sharp rise in intraocular pressure, to as high as 80 mm Hg, followed by a time-dependent decline was found. The application of this ring also caused astigmatic changes in the cornea. Corneal thickening was also encountered. These findings have implications for possible artifactual changes during photorefractive keratoplasty and raise the possibility of intraocular pressure-induced damage in susceptible individuals. PMID- 8458229 TI - Intrastromal crystalline deposits following hydrogel keratophakia in monkeys. AB - Intrastromal corneal crystals developed in 11 of 49 monkey eyes with hydrogel intracorneal lenticules followed over a 4 year period. All of the eyes, except one, underwent synthetic keratophakia via a microkeratome incision. The diagnosis of crystal formation was initially made by slit-lamp examination and confirmed with specular microscopy (from 21 to 150 days post-hydrogel keratophakia). The crystals were noted to lie in a plane adjacent to the hydrogel lenticule and specular microscopy revealed polychromatic, hyperrefringent crystals with either a rectangular or linear morphology. Prior to intrastromal crystal formation, these corneas developed early postoperative stromal edema (< 3 weeks). We hypothesize that early stromal edema in combination with the hydrogel intracorneal lenticule induced the production of lipid crystals by stromal keratocytes. PMID- 8458231 TI - Regulation of mitogen-driven lymphoreticular cell activation by human corneal cells and interleukin-1. AB - Keratin-positive fibroblast-like epithelial cells (FLE), isolated from human corneo-scleral-conjunctival rims, were shown to inhibit mitogen-driven (concanavalin A) DNA synthesis by murine thymocytes and splenocytes [lymphoreticular cells (LRC)]. The effect exerted by live cells in culture and by their supernatants was caused by factors active across species barriers. Paraformaldehyde-fixed or irradiated cells also suppressed mitogen-induced thymocyte DNA synthesis, but their supernatants manifested no such activity. Interaction between FLE cells and LRC in the presence of the mitogen resulted in suppressed cellular activation as evidenced by significantly lowered tetrazolium salt (MTT) reduction in murine thymocytes and splenocytes, suggesting reduced mitochondrial activity. The suppressive effect was seen with live and paraformaldehyde-fixed FLE cells. There was a good correlation between MTT assays and [3H]thymidine uptake experiments. Suppression of MTT reduction in murine thymocytes and splenocytes by intact FLE cells could be reversed by the addition of interleukin-1 (IL-1). Indomethacin prevented FLE-conditioned medium-induced suppression but failed to relieve suppression by whole FLE cells. Thus, suppression of LRC function by FLE cells and their secretions appeared to operate by different mechanisms. One mechanism related to prostaglandins present in FLE cell-conditioned medium, whereas another mechanism appeared to involve cell membrane-associated factor(s). The findings not only provide additional information on the capability of corneal cells to regulate lymphoreticular cells but suggest an important role for IL-1 in the regulation of LRC function and corneal inflammation and immunity. PMID- 8458230 TI - Synthetic epikeratoplasty in rhesus monkeys with human type IV collagen. AB - Human type IV collagen discs were found to support proliferation and adhesion of rabbit corneal epithelial cells in tissue culture. To assess the biocompatibility of this synthetic collagen for epikeratoplasty, seven eyes of seven rhesus monkeys underwent epikeratoplasty with lenticules made of human type IV collagen. Eye rubbing by the animals expulsed two of the lenticules and caused failure of two to epithelialize completely. The remaining three lenticules epithelialized, remained clear, and caused no adverse effects on the eye. Two of these lenticules developed focal areas of subepithelial thinning 3 months postoperatively and the third lenticule has remained stable for 30 months. The presence of epithelial attachment components at the epithelial-lenticule interface was demonstrated by immunolocalization. Histopathologic and ultrastructural examination revealed focal areas of epithelial invasion and degradation of the lenticule. Neutral proteases were detected in the thinning region of one specimen. Human type IV collagen supports epithelialization in vivo and may have potential as a biomaterial for epikeratoplasty, but the stability of the material must be improved. PMID- 8458232 TI - Corneal abnormalities in Ehlers-Danlos syndrome type VI. AB - Eleven patients with blue sclera, limbus-to-limbus corneal thinning, hypermobile joints, and consanguineous parents were examined between January 1983 and September 1991. The clinical diagnosis was consistent with the Ehlers-Danlos syndrome type VI phenotype in all patients. A "halo" sign at the limbus was present in all patients. Corneal rupture occurred in seven patients (nine eyes) either spontaneously or following minimal trauma. Acute hydrops occurred in three patients. Bilateral microcornea was present in one patient and two patients had a unilateral increased corneal diameter as a result of secondary glaucoma after trauma. Peripheral sclerocornea was present bilaterally in five patients. Curvature abnormalities included cornea plana, keratoconus, and keratoglobus. PMID- 8458233 TI - Piggyback lenses in keratoconus. AB - Intolerance to rigid contact lenses in keratoconus may occur as a result of epithelial pathology or a suboptimal fitting. The application of a soft lens as a bandage makes it possible to tolerate a rigid lens over it. This study gives the results of 40 eyes in 26 patients who were consecutively fitted with a new aspheric combination lens. Thirty-five eyes (87.5%) showed no discomfort, acceptable wearing time, and visual acuity. Four of these eyes showed an improvement of the corneal condition, eliminating the need for a further piggyback wearing system. Failures were found in five eyes (12.5%), which were caused by giant papillary conjunctivitis (two eyes), severe keratoconus (one eye), difficulty in lens handling and lack of motivation (two eyes). The successful use of an aspheric piggyback combination lens in rigid lens-intolerant keratoconus may preclude early surgical therapy. PMID- 8458234 TI - Epithelial transformation of the corneal endothelium in forceps birth-injury associated keratopathy. AB - Using light and electron microscopy, we studied four keratectomy specimens obtained by penetrating keratoplasty from four patients (ages 33-54 years; mean age: 43 years old) who had clinical evidence of Descemet's folds and bullous keratopathy after ruptures in Descemet's membrane after forceps injury at birth. Histopathologically, three patients showed the typical features of forceps birth injury: Descemet's membrane at the margin of the rupture was folded and assumed a scroll-shape configuration. The fourth patient showed clusters of proliferated endothelial cells at the site of two ruptures, and from one site of the ruptures, these cells invaded into Descemet's membrane, forming a new basement membrane. Transmission electron microscopy revealed that these proliferated cells were epithelial-like cells characterized by desmosomal junctions, basal lamina, numerous microvilli, and 8-nm cytoplasmic filaments. The epithelial transformation of the corneal endothelium was identified in cases of posterior polymorphous dystrophy and assumed to be specific for this entity. The findings in our fourth patient represent the first documentation of epithelial-like cells on the posterior corneal surface in forceps birth-injury-associated keratopathy. Our results suggest that epithelial transformation may be a nonspecific reaction of the young cornea to various stimuli. PMID- 8458235 TI - Calcific band keratopathy on a keratoprosthesis. AB - We describe a case of calcific band keratopathy in a patient with a nut-and-bolt keratoprosthesis. To our knowledge, this is the first reported case of this condition involving a prosthesis. The patient had initially suffered lye burns to both eyes. The prosthesis was placed in the right eye; numerous procedures had to be undertaken to maintain it. The patient was also treated surgically and pharmacologically for glaucoma. Seventeen years after initial implantation, white flakes appeared on the prosthesis in the classical band pattern. Pathologic examination revealed them to be calcific. Theories concerning corneal and contact lens calcific deposition are evaluated to assess their applicability to this case. We conclude that multiple factors may be responsible for calcific deposition on the keratoprosthesis and that this may call into question previous explanations of this disorder. PMID- 8458236 TI - Pseudo-Kayser-Fleischer ring of the cornea associated with non-Wilsonian liver disease. A case report and literature review. AB - The Kayser-Fleischer ring of the cornea is usually considered a pathognomonic finding of Wilson's disease. A case of a Kayser-Fleischer ring associated with non-Wilsonian liver disease is presented. The pathophysiology of copper deposition in the cornea and the differential diagnosis of this rare finding are discussed. PMID- 8458237 TI - Unusual causes of giant papillary conjunctivitis. AB - We report two unusual causes of giant papillary conjunctivitis (GPC). One patient developed GPC secondary to and elevated filtering bleb. Another patient developed focal GPC secondary to elevated calcific plaques (band keratopathy). The first patient's symptoms improved after treatment with sodium cromolyn drops. GPC resolved in the second patient after superficial keratectomy was performed. These cases represent two unusual causes of GPC and emphasize the role of mechanical trauma as a causative factor. PMID- 8458238 TI - Treatment of an alkali burn-induced symblepharon with a Megasoft Bandage Lens. AB - Chemical burning of the external eye by a strong acid or alkali often results in symblepharon formation despite conventional therapy. We report a case with application of a Megasoft Bandage Lens to prevent symblepharon reformation after surgical correction. Complete epithelial healing was established after 3 months, when the lens could be removed. No complications were found with this lens. No symblepharon reformation occurred < or = 6 months after the surgical reconstruction. PMID- 8458239 TI - Human infectious corneal ulcer caused by Pythium insidiosum. AB - Pythium insidiosum is a fungus-like organism known to infect a variety of animals. In humans, the few known cases involving Pythium have included arterial infections and cellulitis. We present what we believe to be the first case of P. insidiosum recovered from a human corneal ulcer. The organism is difficult to isolate, causing delays in diagnosis. It is also resistant to the usual antifungal medications, making surgical excision the treatment of choice. PMID- 8458240 TI - Attribution of previous work. PMID- 8458241 TI - Crohn's disease. PMID- 8458242 TI - Effect of subinhibitory concentrations of Ciprofloxacin and gentamicin on the adherence of Pseudomonas aeruginosa to Vero cells and voided uroepithelial cells. AB - The effect of subinhibitory concentrations (1/8 x, 1/16 x, 1/32 x MIC) of ciprofloxacin or gentamicin on the adherence of Pseudomonas aeruginosa to Vero cells and voided uroepithelial cells was studied using two different assay methods. Strains studied included both reference strains and clinical strains, including mucoid and nonmucoid isolates. Sub-MICs of ciprofloxacin decreased adherence to Vero cells and voided uroepithelial cells in 3 of 4 ciprofloxacin susceptible nonmucoid isolates but not in ciprofloxacin-resistant or mucoid isolates. Sub-MICs of gentamicin significantly reduced adherence in 5 of 7 nonmucoid strains but not in mucoid strains. Gentamicin effect on adherence did not correlate with susceptibility to ciprofloxacin. We conclude that ciprofloxacin susceptibility determines the effect of sub-MICs of ciprofloxacin on P. aeruginosa adherence to Vero cells and voided uroepithelial cells. In addition, both the Vero cell assay and voided uroepithelial cell assay demonstrated similar results. PMID- 8458243 TI - In vitro activity of cefdinir (FK 482, PD 134393, CI-983): a new orally active cephalosporin. AB - Cefdinir is a new orally active cephalosporin which is undergoing in vitro and in vivo evaluations. Using the standard agar dilution method we compared the in vitro activity of this drug with other beta-lactam antibiotics against clinical isolates or Enterobacteriaceae (625 strains), Pseudomonas aeruginosa (68 strains), Xanthomonas maltophilia (36 strains), Acinetobacter (52 strains), Aeromonas hydrophilia (47 strains), staphylococci (364 strains) and enterococci (50 strains). Against most members of Enterobacteriaceae, Acinetobacter and A. hydrophilia, cefdinir showed excellent activity, inhibiting 94% of these isolates at < or = 32 micrograms/ml. Like other oral drugs of its class, it had little activity against P. aeruginosa and X. maltophilia. All the 120 isolates of methicillin-susceptible Staphylococcus aureus were inhibited by < 1.0 microgram/ml of cefdinir whereas 80% of methicillin-resistant S. aureus had a minimum inhibitory concentration of > 32 micrograms/ml. Of the 50 isolates of enterococci tested, 94% were inhibited by < or = 16.0 micrograms/ml of cefdinir. Against Enterobacteriaceae, its activity was superior to any oral drug tested. With the exception of vancomycin, the in vitro activity of cefdinir was superior or comparable to other antibiotics tested against methicillin-susceptible S. aureus, coagulase-negative staphylococci and enterococci. PMID- 8458244 TI - In vitro activity of levofloxacin, ofloxacin and other quinolones against coagulase-negative staphylococci. AB - The in vitro activity of levofloxacin against coagulase-negative staphylococci (CNS) was investigated. In vitro, on the basis of MIC90 values, levofloxacin was as active as ciprofloxacin, inhibiting both methicillin-sensitive and -resistant staphylococci at 0.5 microgram/ml. The frequency of one-step development of levofloxacin-resistant CNS was < 1 x 10(-9). After repeated transfer of CNS in the presence of increasing concentrations of levofloxacin or other quinolones, there were 4-fold increases in MIC50 values for both levofloxacin and ofloxacin, whereas there were 64- to 128-fold increases for ciprofloxacin, norfloxacin and enoxacin. Based on MIC50 values, the concentrations of 1 or 2 micrograms/ml are clinically relevant. The mutant strains induced by levofloxacin showed less virulence based on the LD50 value in acute systemic murine infection. PMID- 8458245 TI - In vitro activity of a new antibacterial drug, trospectomycin sulphate (U 63,366F), against Bacteroides strains isolated from the vagina. AB - The antibacterial activity of trospectomycin, clindamycin, metronidazole, imipenem, cefoxitin, and piperacillin was tested against 72 Bacteroides spp. strains isolated from the vagina of women with vaginitis by determining the minimal inhibitory concentration using the agar dilution method. Trospectomycin shows a good activity which is comparable to that of imipenem and metronidazole. Its expanded spectrum of activity makes trospectomycin suitable for the use in single-drug therapy of pelvic infections in women. PMID- 8458246 TI - Antitumor effect of chemically synthesized (+)-goniopypyrone. AB - Chemically synthesized (+)-goniopypyrone was found to suppress the growth of cultured Ehrlich ascites tumor cells as well as PU5-1.8 cells. The ED50 values were found to be 35 and 30 micrograms/ml for the two cell lines used. An LD50 of 193 micrograms/ml was observed in the brine shrimp bioassay. PMID- 8458247 TI - Amoxycillin and clavulanic acid versus cefotaxime and metronidazole as antibiotic prophylaxis in elective colorectal resectional surgery. AB - In a prospective randomised controlled trial, amoxycillin plus clavulanic acid was compared to a combination of cefotaxime and metronidazole as prophylactic antibiotics in 164 patients who underwent elective colorectal resectional surgery. Wound infection occurred in 15 patients (9.1%) and deep surgical infection in 4 (2.4%). Seven cases of wound infection and 2 cases of deep infection occurred in the amoxycillin plus clavulanic acid arm, while 8 cases of wound infection and 2 cases of deep infection occurred in the cefotaxime plus metronidazole arm. Eighty-eight percent of infections occurred in patients who had low anterior resection or abdominoperineal resection of the rectum. Both the amoxycillin plus clavulanic acid and the combination of cefotaxime and metronidazole offer the same degree of protection against post-operative infection. The use of amoxycillin plus clavulanic acid as antibiotic prophylaxis is recommended because of its easier use and cheaper cost. PMID- 8458248 TI - Ceftriaxone plus conventional or single-daily dose amikacin versus ceftazidime/amikacin as empiric therapy in febrile neutropenic patients. AB - Results of antibiotic treatment in 144 febrile episodes during drug-induced granulocytopenia are reported. 63 episodes were treated with ceftazidime plus amikacin and 81 with ceftriaxone (CFX) using single daily doses combined with amikacin either divided in three doses (CFX-1 group) or administered as single doses (CFX-2 group). The response rates were 51, 80, and 57% respectively. In this study CFX was more effective than ceftazidime and amikacin provided better results when administered using the standard 8-hour scheduling. PMID- 8458249 TI - Maternal and fetal serum and tissue levels of ceftriaxone following preoperative prophylaxis in emergency cesarean section. AB - The use of antibiotic prophylaxis in emergency cesarean section has become the standard of care. Concern over fetal exposure has been the reason that antibiotics are traditionally given post cord clamping, but this does not allow adequate antibiotic levels in maternal blood and tissue to be achieved at the stage of incision and during surgery. We evaluated by bioassay maternal and fetal serum and placental ceftriaxone concentrations following the intravenous administration of 1.0 g of ceftriaxone upon the decision to perform cesarean section. The preoperative prophylaxis with ceftriaxone resulted in adequate protective levels in the mother and very low fetal blood levels. PMID- 8458250 TI - Simple combined agar-strip test for detection of enterococcal susceptibility to ampicillin, moderate- or high-level gentamicin resistance and potential additive activity of ampicillin plus gentamicin. AB - A simple combined agar-strip test (CAST), involving filter paper strips charged with 20 micrograms of ampicillin or 40 micrograms of gentamicin, accurately detected high-level gentamicin resistance among 43 of 146 isolates of Enterococcus faecalis and additive activity of ampicillin plus gentamicin against 101 of 103 (98%) isolates of E. faecalis with moderate-level gentamicin resistance (MLGR). All 15 MLGR Enterococcus faecium isolates were moderately to highly resistant to ampicillin; 5 isolates with moderate resistance to ampicillin (minimal inhibitory concentrations = 16 micrograms/ml) were additively inhibited by ampicillin plus gentamicin, whereas the highly ampicillin-resistant E. faecium isolates yielded an indifferent effect with the CAST procedure. PMID- 8458251 TI - Characterization of BRO enzymes and beta-lactamase transfer of Moraxella (Branhamella) catarrhalis isolated in Japan. AB - Of the 68 strains of beta-lactamase-producing Moraxella (Branhamella) catarrhalis isolated in Japan that were studied, 62 (91%) produced the BRO-1-type beta lactamase and 6 (9%) produced the BRO-2 type. There were no strains containing the BRO-3-type beta-lactamase. We compared the susceptibility of BRO-1- and BRO-2 producing strains to various oral beta-lactam antibiotics. We found that the BRO 1-producing strains were less susceptible than the BRO-2-producing strains. Although the BRO-1 and BRO-2 types showed a similar hydrolysis pattern, the specific activity of BRO-1 was 3-fold that of BRO-2. We examined the transfer of the BRO-1 and BRO-2 genes to non-beta-lactamase-producing M. catarrhalis No. 4020 and found that of the 13 donor strains producing BRO-1, 11 (85%) were able to transfer the gene for BRO-1 production by conjugation. Of the 6 donor strains producing BRO-2, 2 (33%) were able to transfer the gene for BRO-2 production by conjugation. For 3 of the 13 (23%) BRO-1-producing strains and 1 of the 6 (17%) BRO-2-producing strains, about 13 Mdalton of plasmids were detected. These plasmid-containing strains were used as donors, and in beta-lactamase-producing transconjugants the same size of plasmids was detected. However, when the total DNA is extracted from strains with the ability to transfer by conjugation, the transformation of the beta-lactamase-producing gene can occur regardless of the presence or absence of plasmids. Furthermore, even if purified plasmids are transformed, beta-lactamase-producing transformants are not obtained.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458252 TI - Antibacterial activity of cefcanel. AB - The minimum inhibitory concentration of cefcanel, a new oral cephalosporin, has been determined for 182 clinical isolates, of which 84 were from the family Enterobacteriaceae, 45 were from the genus Streptococcus, 18 were nonfermentative rods, 25 were Haemophilus influenzae and 10 were Branhamella catarrhalis. In general, cefcanel was more active than the other cephalosporins against the species Escherichia coli, Klebsiella aerogenes and Proteus mirabilis. Among the genus Streptococcus only the enterococci were resistant to cefcanel. H. influenzae and B. catarrhalis showed also a reasonable susceptibility towards cefcanel. Oxidative rods were highly resistant to cefcanel. PMID- 8458253 TI - Mechanism of chromosome elimination in the hybridogenetic spermatogenesis of allotriploid males between Japanese and European water frogs. AB - Of 21 allotriploid males that possessed two genomes of Rana nigromaculata and one genome of Rana lessonae 10 produced a large number of spermatozoa in their testes. When 4 of these males were backcrossed with a female of R. nigromaculata, all of the resulting froglets were diploid in chromosome number and were completely R. nigromaculata type in appearance. These allotriploid males proved to have produced spermatozoa with one R. nigromaculata genome hybridogenetically. Therefore, their germ line cells were investigated for the mechanism of elimination of their R. lessonae chromosomes. In histological sections of testes, the great majority of spermatogonia (approximately 10(4) cells) between mitotic prometaphase and anaphase appeared normal in chromosome behavior, whereas 17 spermatogonia showed several chromosomes whose behavior deviated from the normal course during the same period. These deviant chromosomes concentrated together near the equatorial plate and remained stationary at anaphase. In metaphase chromosome preparations made from spermatogonia, 67 and 185 of the 477 chromosome spreads were diploid and triploid, respectively. The rest were aneuploid. Notably, 8 triploid spreads consisted of 26 or more normal chromosomes and 13 or fewer degenerate chromosomes. From these results it is concluded that a set of R. lessonae chromosomes is eliminated from some, but not all spermatogonia by becoming degenerate during the mitotic period. PMID- 8458254 TI - Germ line-restricted, highly repeated DNA sequences and their chromosomal localization in a Japanese hagfish (Eptatretus okinoseanus). AB - The various species of Japanese hagfish, namely, Eptatretus okinoseanus (types A and B), Eptatretus burgeri and Myxine garmani, are known to eliminate a fraction of their chromosomes during early embryogenesis. High molecular weight DNA from germ line cells and somatic cells of these hagfish species was isolated and digested with different restriction enzymes. The DNA fragments were separated by agarose gel electrophoresis. Digestion with BamHI and DraI generated two weak bands and one weak band, respectively, that were estimated to be about 90, and 180 bp and about 90 bp long and were limited to the germ line DNA in both types of E. okinoseanus. DNA filter hybridization experiments showed that the two BamHI fragments and the one DraI fragment were present almost exclusively in the germ line DNA of E. okinoseanus. Thus, these DNA fragments appear to be eliminated during embryogenesis. Moreover, evidence was obtained that these fragments are highly and tandemly repeated. Molecular cloning and sequence analysis revealed that the BamHI fragments are mainly composed of a family of closely related sequences that are 95 bp long (EEEo1, for Eliminated Element of E. okinoseanus 1), and the DraI fragment is composed of another family of closely related sequences that are 85 bp long (EEEo2). The two DNA families account for about 19% of the total eliminated DNA in E. okinoseanus type A. Fluorescence in situ hybridization experiments demonstrated that the two families of DNA are located on several C-band-positive, small chromosomes that are limited to germ cells in both types of E. okinoseanus. PMID- 8458255 TI - Saccharomyces cerevisiae linear chromosome stability (lcs) mutants increase the loss rate of artificial and natural linear chromosomes. AB - We isolated mutants of Saccharomyces cerevisiae that lose a 100 kb linear yeast artificial chromosome (YAC) at elevated rates. Mutations in two of these LCS (linear chromosome stability) genes had little or no effect on the loss rate of a circular YAC that had the same centromere and origin of replication as present on the linear YAC. Moreover, mutations in these LCS genes also increased the loss rate of an authentic linear yeast chromosome, chromosome III, but had only small effects on the loss rate of a circular derivative of chromosome III. As these mutants preferentially destabilize linear chromosomes, they may affect chromosome stability through interactions at telomeres. Telomeres are thought to be essential for the protection and complete replication of chromosome ends. The cytological properties of telomeres suggest that these structures may play additional roles in chromosome function. The lengths of the terminal C1-3A repeats at the ends of yeast chromosomes were unaltered in the linear preferential lcs mutants, suggesting that these mutants do not affect the replication or protection of telomeric DNA. Thus, the linear-preferential lcs mutants may identify a role for telomeres in chromosome stability that is distinct from their function in the replication and protection of chromosomal termini. PMID- 8458256 TI - Peritoneal carcinomatosis from appendiceal cancer: results in 69 patients treated by cytoreductive surgery and intraperitoneal chemotherapy. AB - Sixty-nine patients presenting over a 10-year period with peritoneal carcinomatosis from appendiceal cancer were treated with cytoreductive surgery combined with intraperitoneal chemotherapy. The three-year survival is 89.5 percent in patients (38/69) with pseudomyxoma peritonei, 34.5 percent in patients (25/69) with cystadenocarcinoma, and 38.1 percent in patients (6/69) with adenocarcinoma (P < 0.01). In this study, a classification of residual disease following the cytoreductive surgery was used. The prognosis of the patients with minimal residual disease was better than that of those with moderate or gross disease, showing a 91.6 percent three-year survival compared with 47.8 percent and 20 percent, respectively (P < 0.01). The patients without lymphatic or hematogenous metastases had a better three-year survival than those with metastases (75.1 percent vs. 28.6 percent; P < 0.01). These findings suggest that peritoneal carcinomatosis from appendiceal cancer can be treated with long-term disease-free survival. The patients with low malignant potential cancer, complete cytoreduction, and no metastases showed the most effective disease control. PMID- 8458257 TI - Effects of trimebutine on colonic function in patients with chronic idiopathic constipation: evidence for the need of a physiologic rather than clinical selection. AB - A double-blind crossover study on the effects of trimebutine on large bowel function was performed in 24 consecutive patients complaining of chronic idiopathic constipation. Their stool frequency, colonic transit time, and colonic electrical activity were measured. They were divided into a group of constipated patients with "normal" transit time (less than 40 hours) (n = 12) and another group of constipated patients with "delayed" transit time (more than 40 hours) (n = 12). The patients received trimebutine (200 mg/day per os) for one month and a placebo for another month, at random, with a washout period in between. Results show that stool frequency increased (P < 0.001) in all patients as soon as they entered the study; there was no difference between trimebutine and placebo. Colonic transit time was significantly reduced (P < 0.05) with trimebutine in patients with delayed transit time (from 105 +/- 19 hours to 60 +/- 11 hours; mean +/- SE), while it did not change with placebo (from 103 +/- 17 hours to 95 +/- 10 hours). It was slightly but not significantly increased in patients with normal transit time following trimebutine therapy. Electrical activity was not influenced by trimebutine or placebo in constipated patients with normal transit time, either before or after a meal. The number of propagating bursts during the postprandial period was significantly (P < 0.05) increased in patients with delayed transit (from 2.1 +/- 0.3 bursts/hour to 3.5 +/- 0.6 bursts/hour after trimebutine); it was decreased but not significantly with placebo (from 2.6 +/- 0.8 bursts/hour to 1.6 +/- 0.6 bursts/hour) in the same group of patients. Thus, stool frequency in patients with chronic idiopathic constipation was influenced mainly by a placebo effect. Colonic transit time was reduced by trimebutine, but this was found only in patients with delayed colonic transit; myoelectric propagating bursts were increased, and this probably explains the improvement. In conclusion, trimebutine may be of value in the treatment of patients with chronic idiopathic constipation, provided that a careful pathophysiologic evaluation reveals that they have a colonic transit time that exceeds the normal range. In addition, this study provides some argument for selecting patients with functional motor disorders of the large intestine to be entered into a research protocol or to be treated not on the basis of what they complain about--the symptom--but on the basis of some kind of measurement of dysfunction--a corresponding sign. PMID- 8458258 TI - Relationship between anal canal tone and rectal motor activity. AB - The anal sphincters facilitate fecal continence by maintaining a pressure barrier; whether proximal contractile events influence this barrier is unknown. The aim of this study was to determine whether a relationship exists between anal canal pressures and rectal motor activity. A fully ambulatory system for prolonged pressure recording was developed. In 12 healthy subjects (seven males and five females; mean age, 35 years; range, 22-43 years), a flexible transducer catheter (outside diameter, 4.5 mm) was introduced endoscopically such that sensors were 2, 3, 8, 12, 18, and 24 cm from the anal orifice. Twenty-four-hour spontaneous motor activity was stored in a 2.5-megabyte portable recorder for later transfer to a Microvax II for computerized analysis and display. Mean anal canal pressure was calculated, and rectal motor complexes (RMCs) were characterized. Mean and canal resting pressure was 75 +/- 12 mmHg. During sleep, anal pressures displayed cyclic decreases (mean periodicity, 1.6 hours; range, 1 4 hours), during which the mean +/- SD pressure trough was 15 +/- 4 mmHg (range, 8-21 mmHg). RMCs were identified in all subjects: mean frequency, 16 per 24 hours (range, 12-22 per 24 hours); duration, 15.3 minutes (range, 8-35 minutes); contractile frequency, two to three per minute; mean peak amplitudes, 58 +/- 18 mmHg; and periodicity, 78 +/- 24 minutes (range, 35-265 minutes). Importantly, an RMC was invariably accompanied by a rise in mean anal canal pressure and contractile activity such that pressure in the anal canal was always greater than pressure in the rectum. Anal canal relaxations never occurred during an RMC. Motor activities of the rectum and of the anal canal may be related; the onset of rectal contractions was accompanied by increased resting pressure and contractile activity of the anal canal. This temporal relationship represents an important mechanism preserving fecal continence. PMID- 8458259 TI - Previous subtotal colectomy with ileostomy and sigmoidostomy improves the morbidity and early functional results after ileal pouch-anal anastomosis in ulcerative colitis. AB - The aim of this work was to study the effects of previous subtotal colectomy (STC) with ileostomy and sigmoidostomy on the outcome of ileal J-pouch-anal anastomosis (IPAA) in patients with acute ulcerative colitis. Between 1983 and 1991, we conducted a prospective, nonrandomized study of 156 patients who underwent IPAA in our center. Fifty-five patients (34.3 percent) had undergone STC with ileostomy and sigmoidostomy for either severe acute colitis (36.5 percent of cases) or nonresolving acute colitis (63.5 percent) up to six months before IPAA with covering ileostomy. There were no perioperative deaths; six patients (11 percent) developed complications requiring reoperation (three cases of pelvic sepsis, two occlusions, and one stenosis of the ileostomy). IPAA was successfully carried out at a later stage in all cases. The results of IPAA in these patients were compared with those in 78 patients who underwent the classical two-stage IPAA procedure. The rates of pelvic sepsis and postoperative occlusion were lower in the subgroup of patients who underwent the three-step procedure. Three months after closure of the ileostomy, the mean number of daily stools was significantly lower in the patients who had undergone prior STC (5.09 vs. 5.9), but there was no significant difference between the two groups with regard to diurnal and nocturnal continence, the need to wear a pad, discrimination between gas and stools, or the use of antidiarrheal medication. In addition, there was no significant difference at one year in terms of functional parameters. We conclude that STC is a simple and safe procedure for the treatment of a severe attack of colitis and that it does not compromise the results of later IPAA. Because it does not increase the morbidity of subsequent IPAA and is associated with more rapid functional recovery, STC appears to be suitable for the treatment of patients with nonresolving acute colitis before the onset of malnutrition or steroid dependency. PMID- 8458260 TI - Loop ileostomy is a safe option for fecal diversion. AB - This study was undertaken to prospectively assess all morbidity and mortality associated with temporary loop ileostomy. Eighty-three consecutive patients of a median age of 45 years required temporary fecal diversion after either ileoanal or low colorectal anastomosis (n = 72), for perianal Crohn's disease (n = 5), or for other reasons (n = 6). All loop ileostomies were supported with a rod, and fecal diversion was maintained for a mean of 10 weeks. To date, 67 patients have had re-establishment of intestinal continuity. Stoma closure was affected through a parastomal incision in 64 patients; in three, a laparotomy was required. The closure was stapled side to side in 49 patients, while a hand-sewn anastomosis was done in the other 18 patients; all skin wounds were left open. The mean length of surgery for ileostomy closure was 56 minutes, and the mean hospital stay was five days. Nine patients (10.8 percent) developed 10 complications, nine of which required hospitalization. Specifically, four patients developed dehydration and electrolyte abnormalities secondary to high stoma output, and two had anastomotic leaks that spontaneously healed following conservative management. One patient developed a superficial wound infection that spontaneously drained itself. One patient developed a partial small bowel obstruction that resolved without surgery after a four-day hospitalization. One stoma retracted after supporting rod removal and prompted premature closure. There was no stomal ischemia, hemorrhage, prolapse, or mortality in this series. Thus, loop ileostomy is a safe way to achieve fecal diversion. PMID- 8458261 TI - Long-term follow-up of strictureplasty in Crohn's disease. AB - Because Crohn's disease of the small bowel is often diffuse, strictureplasty has been advocated as an alternative or adjunct to resection(s) of strictured segments. We reviewed 116 patients with obstructive Crohn's disease undergoing 452 primary strictureplasties (Heineke-Mikulicz, 405; Finney, 47). The median age was 34 years (range, 13-72 years); the male-to-female ratio 1.4:1; and the median follow-up was three years (range, six months to seven years). Seventy-six patients (66 percent) had at least one previous small bowel resection. Perforative disease was present in 18 patients (15 percent), and synchronous resections were performed in 71 patients (61 percent). The median number of strictureplasties was three (range, 1-15). There was no mortality. Septic complications (intra-abdominal abscess/fistula) occurred in seven patients (6 percent), and reoperation for sepsis was needed in two patients. Relief of obstructive symptoms was achieved in 99 percent of the patients. After surgery, the median weight gain was 4 kg, and two-thirds of the patients were weaned off steroids. Symptomatic recurrence occurred in 28 patients (24 percent), and 17 patients (15 percent) needed reoperation. Rates of restricture and new stricture/perforative disease were 2.8 percent and 24 percent, respectively. PMID- 8458262 TI - What happens to the Valtrac anastomosis of the colon? A follow-up study. AB - Late results after colonic anastomoses performed with the biofragmentable anastomosis ring (BAR; Valtrac; Davis & Geck, Wayne, NJ) were evaluated in 30 patients who had undergone a left-sided colonic or rectosigmoid anastomosis a mean of 24.5 (range, 12-38) months earlier. Patients were asked about their late postoperative recovery and their bowel habits. A barium enema was performed, and then a flexible endoscopy was done, during which the anastomotic area was evaluated both in macroscopic terms and histologically. One of the patients had died, and three refused to participate in the investigation. Of the remaining 26 patients, one had been reoperated on 22 months after the primary sigmoid resection. The reason for reoperation was an anastomotic stricture. One of the patients was admitted to the hospital during the study and was operated on for reasons not related to the anastomosis. Twenty-four patients underwent the study scheme. All had recovered uneventfully. Sixteen anastomoses could not be identified radiologically and seven not even during endoscopy. Histologically, there was mild-to-moderate fibrosis and scarring in 17 anastomoses, and, in the seven that could not be identified, only normal colonic mucosa was found. The late results of BAR anastomoses are satisfying, and the rate of complications is acceptable. PMID- 8458263 TI - Diversion colitis in patients scheduled for colostomy closure. AB - Despite recent work, diversion colitis remains poorly defined. Thirty-four patients, scheduled for colostomy closure, were prospectively evaluated with flexible sigmoidoscopy for diversion colitis. Biopsies and cultures were obtained if colitis was identified at endoscopy. All biopsy materials and cultures were consistent with inflammation only. The vast majority of patients were in good general health, and their colostomies were constructed as the result of trauma. Eight patients (24 percent) had normal-appearing colons at an average of 16.6 weeks following diversion. Twenty-six patients (76 percent) demonstrated mild to severe colitis at an average of 29.9 weeks following diversion. Three complications occurred in 22 patients after colostomy closure: two wound infections in patients with colitis and one in a patient with a normal colon. We conclude that diversion colitis in an otherwise individual constitutes no increased risk of infection following colostomy closure. PMID- 8458264 TI - Colonoscopy in patients with benign anorectal disease. AB - A prospective study was performed to determine the incidence of colorectal neoplasia and inflammatory bowel disease in patients with benign anorectal disease. Over a three-year period, 102 consecutive patients who presented with hemorrhoids, fissure, fistula-in-ano, anorectal abscess, and anal condylomata and who did not have gastrointestinal symptoms underwent colonoscopy. The mean age of all patients was 53.5 years; males out-numbered females 1.6:1. No patient was found to have inflammatory bowel disease. Ten of 102 (9.8 percent) were found to have a neoplastic lesion (nine adenomas and one adenocarcinoma). Patients found to have a neoplastic lesion tended to be older (61 years vs. 52.7 years; P = 0.06). Neoplasia was found in 4 of 21 (19 percent) with a family history of colorectal cancer and in 6 of 81 (7.4 percent) without a family history (P = 0.24). Patients presenting with outlet-type bleeding were not found to have a higher detection of neoplasia. The specific type of anorectal disease present was not associated with an increased risk for colorectal neoplasia. Our study suggests that benign anorectal disease and colorectal neoplasia may coexist. Anorectal disease is not predictive of neoplasia. The decision to perform colonoscopy should be based on age, gastrointestinal symptoms, and other risk factors. PMID- 8458265 TI - Action of in situ nitroglycerin on upper anal canal pressure of patients with terminal constipation. A pilot study. AB - Nitroglycerin (NTG) in situ reduces the pressure of the upper anal sphincter (UAS). We have tested the effects of NTG on the UAS of patients with terminal constipation. We studied two groups of constipated patients. Group 1 consisted of 11 patients (nine females and two males) with hypertonicity of the UAS (> 70 mm Hg); age was 49.5 +/- 15.6 years. Group 2 consisted of 10 patients (nine females and one male) without hypertonicity; age was 40.1 +/- 14.1 years. Group 3 consisted of eight asymptomatic controls (four females and four males); age was 51.7 +/- 6.9 years. After a 10-minute resting pressure recording of the UAS with a water-filled balloon, the probe was pulled through the outside and the UAS was assessed after spreading 5 mg of placebo and then 5 mg of NTG on the balloon. Resting pressure (RP), delay of the pressure decrease (DP), pressure after five minutes either during the NTG (PN5) or placebo (PP5) period, and mean duration of the pressure decrease (MD) were measured. None of the subjects experienced a decrease of PP5 vs. RP. All patients in Group 1 (106.2 vs. 38.4 mm Hg), Group 2 (57.9 vs. 31.4 mm Hg), and controls (62.2 vs. 33.7 mm Hg) experienced a significant decrease of pressure of the UAS (P < 0.005). Delay of the pressure decrease was less than two minutes, with wide interindividual variability of duration of the pressure decrease. Mild side effects--anal pain and transient headache--were reported in five patients. In situ NTG significantly reduced UAS Pressure in all groups. NTG has to be evaluated in anal pathology, especially in patients with hypertonic sphincter terminal constipation or acute hypertonicity of the sphincter due to a fissure. PMID- 8458266 TI - Adenocarcinoma of the anal glands. Results of a survey. AB - Anal gland adenocarcinoma is rare, with information concerning this lesion communicated mostly as case reports. Cases seen by authors, combined with a survey of the membership of The American Society of Colon and Rectal Surgeons, allowed 52 cases with sufficient data for analysis. It became clear from the survey that most colorectal surgeons have not treated this malignancy. Predominant symptoms are anal pain (58 percent), rectal bleeding (40 percent), and the presence of perianal mass (37 percent). Fifty-four percent of patients present with a fistula, the incidence of fistula being significantly higher in males. Metastases, which may be inguinal, pelvic, or hepatic, are present at diagnosis in 13.5 percent of patients. Three-fourths of patients are eventually treated by abdomino-perineal resection (APR). Twelve percent of the patients in this series had an APR after a failed local excision. The conclusions from this study are: 1) if local excision is attempted, it must be complete, and the patient must be followed closely for many years, and 2) APR is needed in most patients for local control, with the role of subsequent radiation therapy and/or chemotherapy not yet defined. PMID- 8458267 TI - Cumulative incidence of metachronous colorectal cancer. AB - The incidence of metachronous colorectal cancer has most often been reported as a crude rate: second cancers/index cancers. The reported incidence varies between 0.5 percent and 3.6 percent. However, these calculations do not take into account factors such as length of survival and length of follow-up. The cumulative incidence more accurately reflects the risk for developing a metachronous cancer and was determined in a retrospective analysis of 5,476 patients who were diagnosed with colon or rectal cancer between 1965 and 1985. The cumulative probability was calculated by determining the number of patients developing a metachronous colon cancer vs. the number remaining at risk at that point in time. The calculated annual incidence for metachronous tumors was 0.35 percent per year. The cumulative incidence at 18 years was 6.3 percent. Analysis also demonstrated that metachronous cancers were diagnosed at earlier stages than were index cancers (P = 0.03). Subgroup analysis was performed on patients diagnosed with metachronous cancer before and after 1980. There was a difference in the incidence of metachronous cancers between these two groups (P = 0.04). PMID- 8458268 TI - Tauromustine is more effective than conventional chemotherapy in the treatment of colonic tumors. AB - Despite recent advances in chemotherapy, the prognosis of advanced colorectal cancer remains poor. Although the taurine-based nitrosourea tauromustine (TCNU) has demonstrated schedule-dependent synergism with 5-fluorouracil (5-FU) and leucovorin (LV) against a variety of tumors in vitro, its efficacy relative to and in combination with these drugs in vivo remains unknown. To study this, BALB/C mice had C26 tumor implanted subcutaneously five days prior to the following treatment (doses and route of administration being the same in all groups): Group 1--no treatment; Group 2--TCNU (30 mg/kg by gavage); Group 3--LV (100 mg/kg intraperitoneally [IP]) and, one hour later, LV plus 5-FU (100 mg/kg IP); Group 4--LV and, one hour later, LV plus 5-FU and TCNU; and Group 5--TCNU and, on the following day, LV and, one hour later, LV plus 5-FU. All treatments were repeated seven days later. Body weight and tumor weight were measured twice weekly, and survival was noted. Postmortems were performed in all animals, and evidence of primary or secondary tumor was recorded. All surviving animals were sacrificed at 60 days. We found that 1) 87 percent of animals receiving TCNU and 60 percent of animals receiving LV, 5-FU, and TCNU survived to day 60; none of these animals had evidence of tumor when sacrificed; 2) animals in all other groups died by day 34; 3) evidence of metastases was found in five animals in Group 1 and one each in Groups 2 and 5; and 4) administering TCNU 24 hours prior to 5-FU plus LV resulted in death from toxicity in all animals. Thus, while synergism between TCNU and 5-FU plus LV was not seen, the antitumor properties of TCNU are significantly greater than those of conventional chemotherapy. PMID- 8458269 TI - The Colo-Shower: a new irrigator for intraoperative rectal washout. AB - Intraoperative rectal washout reduces rectal bacterial flora concentration and exfoliated tumor cells but compromises operating theater sterility. I present the Colo-Shower (Sapi-Med, Alessandria, Italy), a modified, disposable proctoscope for intraoperative rectal irrigation that, by collecting liquid flowing out of the anus during rectal washout, minimizes operating theater pollution. The Colo Shower, which has now been used on 100 patients who underwent ileorectal or colorectal anastomosis, is effective and easy to use. PMID- 8458270 TI - The two-chamber ileal pelvic reservoir--an alternative design. AB - A new ileal pouch design, combining an upper triplicate ileum with a lower duplicate ileum, is described. The physical characteristics of this two-chamber reservoir would lead to better functional results by delaying the filling time of the reservoir. PMID- 8458271 TI - Clinical experience with local excision and postoperative radiation therapy for rectal cancer. AB - The standard surgical treatment for patients with potentially curable transmural and/or node-positive rectal cancer is a low anterior resection or abdominoperineal resection. There is increasing interest in the use of local excision and postoperative radiation therapy as primary therapy for selected rectal cancers. The limited data suggest that the approach of local excision and postoperative radiation therapy should be limited to patients with either T1 tumors with adverse pathologic factors or T2 tumors. Transmural tumors have a 24 percent local failure rate and are treated more effectively with standard surgery and preoperative or postoperative therapy. The results of local excision and postoperative radiation therapy are encouraging; however, more experience is needed to determine whether this approach ultimately has local control and survival rates similar to standard surgery. PMID- 8458272 TI - Early detection of unsuspected colon cancers in asymptomatic people. PMID- 8458273 TI - Cytopathology in Di-Cy's lifetime. PMID- 8458274 TI - Fine-needle aspiration of the breast: a review of 1,995 cases with emphasis on diagnostic pitfalls. AB - Between 1985 to 1989, 1,995 fine-needle aspirations of palpable breast lesions were performed at our institution. In all cases, the aspirates were procured by cytopathologists using 22- or 23-gauge needles. Direct smears were immediately stained with Diff-Quik and Papanicolaou and assessed for specimen adequacy (criteria as followed in this institution). Tissue follow-up was available in 1,117 cases. The cytologic diagnoses rendered in these cases were: malignant, 690 cases (60.2%); suspicious for carcinoma, 49 cases (4.3%); benign, 343 cases (29.9%), and insufficient specimen, 35 cases (3.1%). There were 28 false-negative and 2 false-positive results. Considering only cases definitively diagnosed as benign or malignant, the sensitivity was 96%, specificity 99%, positive predictive value 99%, negative predictive value 94%, and overall efficiency 97%. Of these specimens considered suspicious, only 11 cases (22%) were proved not to be malignant after excisional biopsy. These were three fibroadenomas, three ductal hyperplasias, two adenosis tumors, two mucocele-like lesions, and one nipple adenoma. The two lesions that resulted in true false-positive diagnoses were an apocrine cyst with atypia and sclerosing adenosis with radial scar. The clinical and cytologic features of the benign conditions that resulted in false suspicious and positive diagnoses and those features that distinguish them from carcinoma are presented. PMID- 8458275 TI - Cytobrush sampling in conjunctival cytology. AB - The cervical cytobrush was used to obtain samples from the temporal bulbar conjunctiva of normal and nonnormal eyes in 54 cases after application of local anesthesia. The cotton swab was also used. All samples were smeared on glass slides, fixed immediately and then stained by a routine Papanicolaou method. On microscopic examination plenty of well preserved cells were present in all smears sampled by the cervical cytobrush. On the contrary, all samples obtained by the cotton swab contained few cells, most of which showed degeneration. The cervical cytobrush is very useful to conjunctival cytology because it provides abundant cellular material and good cell preservation, using standard and simple preparatory methods. PMID- 8458276 TI - Fine-needle aspiration biopsies of metastatic neuroendocrine tumors in liver: use of transmission electron microscopy and protein A gold technique in diagnosis. AB - Five fine-needle aspiration biopsies of liver were studied to evaluate the use of electron microscopy and protein A gold technique in the diagnosis of metastatic neuroendocrine tumors. All five cases had cytologic features suggestive of neuroendocrine tumors and neurosecretory granules on ultrastructural examination. The aspirates were stained by the immunoperoxidase technique and the postembedding protein A gold technique using the antibody to chromogranin A. Three cases were positive for chromogranin A by both immunoperoxidase and protein A gold techniques. Two cases were positive by protein A gold technique and negative by immunoperoxidase technique. Confirmation of neurosecretory granules by immunochemistry is ideal, since ultrastructurally they can be mimicked by other electron-dense inclusions. Advantage of the protein A gold technique is the use of the same material for both ultrastructural evaluation and the protein A gold technique. PMID- 8458277 TI - Cytopathology of malignant mesothelioma: a study of its patterns and histological bases. AB - We have reviewed the effusion cytology of 51 cases of histologically proven malignant mesothelioma of the pleura (49 cases) and the peritoneum (2 cases). The patient group included 45 males and 6 females, aged 45-83 yr. A cytological diagnosis of malignancy had been rendered on 43 cases, and in 30 of them it was consistent with, or at least suggestive of, a mesothelioma. Diagnostic clues, especially evident in epithelial and biphasic tumors were hypercellularity and/or morular aggregates of malignant cells showing scalloped borders and nuclei with dense chromatin and evident nucleoli. Cytomegaly with multinucleation was also frequently observed. Reactive mesothelial cells were often present along with other non specific features such as red blood cells, fibrin, necrotic debris. In 13 cases, a diagnosis of malignancy was entertained but mesothelioma, although considered, was not reported out because of scantiness of material. In four cases, adenocarcinoma was erroneously diagnosed for the presence of deceptive cell vacuoles. In eight cases, no diagnostic cells were recovered in repeated effusions. The first diagnosis was a cytologic one in 37 patients, Tissue study was performed on autopsy (35 patients) and surgical material. The latter was the only source of histology in six cases. Immunocytochemical investigation was negative for carcinoembryonic antigen in all but one tested cases (1/21) and positive for human milk fat globulin in about one-half of the epithelial and biphasic tumors. In 18 of 21 cases, positivity for combined high- and low molecular-weight keratins was detected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458278 TI - Diagnosis of eosinophilic granuloma of bone by fine-needle aspiration with concurrent institution of therapy: a cytologic, histologic, clinical, and radiologic study of 27 cases. AB - Twenty-seven patients with eosinophilic granuloma (EG) of bone seen at our institution between 1979 and 1991 underwent fine-needle aspiration (FNA) with or without concurrent Tru-Cut biopsy. The 16 males and 11 females ranged in age from 2 1/2 to 61 years (median, 10 yr). Twenty-four patients had monostotic lesions. The clinicoradiologic differential diagnosis included osteomyelitis and Ewing's sarcoma (young patients) and primary and metastatic malignancies (older patients). Twenty-four of 28 FNAs (one patient had two FNAs) were diagnostic of EG, and 10 cases were diagnosed by FNA alone. Smears in these cases showed histiocytes, often with grooved or infolded nuclei, and abundant eosinophils. Multinucleated giant cells, foamy histiocytes, neutrophils, lymphocytes, and plasma cells were present in variable numbers. Four FNAs were misdiagnosed: two as osteomyelitis where smears contained abundant neutrophils, sparse eosinophils, and histiocytes misinterpreted as foamy histiocytes, and two as metastatic carcinoma (in adults) where histiocytes in a scant specimen (one case) and skin appendiceal structures without lesional tissue (one case) were misinterpreted. These cases were correctly diagnosed on repeat FNA (one case), Tru-Cut (two cases), or excisional biopsy (one case); however, three cases diagnosed by FNA had nondiagnostic concurrent Tru-Cut biopsies. Treatment consisted of intralesional injection of 125 mg of methylprednisolone (22 cases). Progressive or complete healing of all lesions occurred. FNA is a rapid and useful technique for the immediate diagnosis of EG that allows concurrent institution of therapy. PMID- 8458279 TI - Eight cases of Sister Mary Joseph's nodule diagnosed by fine-needle aspiration. AB - We report eight cases of umbilical metastases (Sister Mary Joseph's nodules) diagnosed by fine-needle aspiration. The primary carcinoma was below the diaphragm in seven patients. There was one false-negative diagnosis. We advocate the use of fine needle aspiration as the initial diagnostic test. It is a simple, fast, accurate, and relatively inexpensive means of making the definitive diagnosis. It can spare patients invasive procedures that are not clearly of benefit. PMID- 8458280 TI - Testicular cytology in azoospermia. AB - Two hundred-seventy-five azoospermic males were subjected to fine-needle aspiration (FNA) cytologic study of testis with the aim of determining the cause of azoospermia; 534 aspirates from these patients were classified as follows: normal spermatogenesis (162), hypospermatogenesis (mild, moderate, or severe, 226), absence of spermatogenesis (130), maturation arrest (36), Sertoli-cell-only syndrome (14), and Leydig-cell hyperplasia (3). The morphology of cells was excellent in the cytologic preparations and various spermatogenic cells and Sertoli cells were easily recognized. Leydig cells were uncommonly seen, except in cases of Leydig-cell hyperplasia. Degenerative changes, possibly due to obstruction, were seen in 104 cases. The procedure was well tolerated by the patients. We conclude that FNA cytology is a useful investigative modality in the evaluation of azoospermic males. PMID- 8458281 TI - Objective comparison of cellular yield in fine-needle biopsy of lymph nodes with and without aspiration. AB - Recent reports have indicated that needle biopsy without aspiration obtained adequate material for diagnosis. To determine objectively the adequacy of cell yield both for diagnosis and for special studies (e.g., flow cytometry, markers), we prospectively studied 20 superficial lymph nodes in 20 patients with a history of lymphoma. In each case, the cytology materials were obtained by fine-needle biopsy techniques with (FNAB) and without (FNB) aspiration. Two needle passes for each method were placed in separate tubes of RPMI medium. With FNAB, the cell counts (determined by a Coulter counter) ranged from 1.55 to 70 million (M) per tube, mean = 19.12 M, whereas with FNB, the cell counts ranged from 1.58 M to 40 M, mean = 15.48 M (P = 0.4555). Although FNAB provided more cells in 12 cases (60%), FNB provided more cells in the remaining 8 cases (40%) (P = 0.9392). Both techniques provided adequate numbers of cells for special studies in all cases. We conclude that FNB can provide an adequate number of cells both for diagnosis and for special studies. PMID- 8458282 TI - Fine-needle aspiration cytology of sarcomatoid renal cell carcinoma: a morphologic and immunocytochemical study of 15 cases. AB - Sarcomatoid renal cell carcinoma (SRCC), which accounts for 5% of all renal cell carcinomas (RCC), has a worse prognosis than conventional nonsarcomatoid RCC, making accurate diagnosis important. This study reports on the morphologic and immunocytochemical features of 15 cases of SRCC (9 primary tumors and 6 metastases) diagnosed by fine-needle aspiration (FNA) biopsy. All but three cases showed a dimorphic cell population consisting of varying proportions of a high grade epithelial component, either clear or granular-cell type and a spindle cell (sarcomatoid) component, of either fibrosarcomatous, malignant fibrous histiocytoma (MFH), or unclassified types. The sarcomatoid component in the biphasic and monophasic tumors stained positively for cytokeratin in 12 of 14 (85%) cases, for vimentin in 10 of 11 (91%) cases, and for muscle-specific action in 4 of 11 (36%) cases. Of note, the three cases that demonstrated a purely sarcomatoid morphology stained positively for cytokeratin. Unlike in studies performed on surgically resected specimens, neither the proportion of the sarcomatoid component nor the presence of necrosis had prognostic significance, the discrepancy most likely being related to the sampling. We conclude that SRCC, both primary and metastatic, can be accurately diagnosed by FNA when cytologic features are evaluated in conjunction with immunocytochemical findings. PMID- 8458283 TI - Detection of growth fraction in tumors by Ki67 monoclonal antibody in cytologic smears: a prospective study of 40 cases. AB - The monoclonal antibody (MAb) Ki67 detects a nuclear antigen in cycling tumor cells. Quantitation of proliferating cells is helpful in predicting the recurrence and metastatic potential of tumors as previously reported. We conducted a prospective study on 40 benign and malignant tumors by performing Ki67 immunocytochemical stains on cytologic smears and their corresponding frozen tissues. Quantitation of Ki67 positive cells was done by counting 300 cells in 5 7 high-power fields in cytologic smears and tissues. Only nuclear or nucleolar immunostaining was considered positive for MAb Ki67. The number of Ki67 positive tumor cells in cytologic smears correlated well with Ki67 positive cells from corresponding tissues. On the average, cytologic smears showed 1.9% higher Ki67 positivity in malignant tumors as compared to their corresponding frozen tissues (P < 0.001). The Ki67 positivity in malignant tumors was found to be significantly higher when compared with benign tumors (P < 0.001). We conclude that cytologic smears can be used for the determination of growth potential in tumors by MAb Ki67. Additionally, cytologic preparations can be used during intraoperative consultations when adequate tissue is not available for the above mentioned study. PMID- 8458284 TI - Fine-needle aspiration diagnosis of ectopic thyroid: report of one case. AB - Fine-needle aspiration (FNA) of a mass of the floor of the mouth in a teenage woman showed many foamy and pigmented histiocytes, cholesterol crystals, and few sheets of follicular cells with paravacuolar granules and cytoplasmic flares. The cytologic findings were consistent with adenomatous thyroid tissue. This was confirmed by subsequent surgical excision and histologic diagnosis of the surgical specimen. The differential diagnosis and value of preoperative diagnosis by FNA of lesions of the floor of the mouth in general and ectopic thyroid in particular, are briefly discussed. PMID- 8458285 TI - Chondromyxoid fibroma: a fine-needle aspiration diagnosis. AB - A 25-yr-old female presented with a slowly progressive swelling, occurring over an 8-yr period, in the right lower leg. The swelling was tender and fixed to the underlying bone. Clinical and radiological diagnosis was giant cell tumor (GCT) of the bone. Aspiration cytology smears were cellular showing an admixture of chondroid, stellate, and fibrocytic cells against a chondroid background. On cytomorphology, a diagnosis of chondromyxoid fibroma (CMF) was made. It was confirmed on histologic examination. PMID- 8458286 TI - Fine-needle aspiration of dermoid cyst of the pancreas: a case report. AB - A 53-yr-old woman presented with a left upper quadrant abdominal mass attached to the body of the pancreas. Fine-needle aspiration (FNA) yielded cyst fluid containing numerous benign, mature squamous cells, keratin debris, and inflammatory cells. The diagnosis of dermoid cyst was subsequently rendered on the resected specimen. The cytologic and histologic features are presented. FNA cytology proves to be a valuable diagnostic adjunct in the preoperative evaluation of a patient with dermoid cyst of the pancreas. PMID- 8458287 TI - Crystalloids in a cystic lesion of parotid salivary gland: diagnosis by fine needle aspiration. AB - Crystalline structures measuring < 800 microns in length, were found in smears of a fine-needle aspirate of a cystic lesion in a parotid salivary gland. Numerous neutrophil leukocytes were also present, intimately mixed with the crystalloids. The lesion was re-aspirated and the cyst completely evacuated, with no recurrence after a 6-month follow up. PMID- 8458288 TI - Microglandular adenosis of the breast: fine-needle aspiration biopsy of two cases. AB - Microglandular adenosis (MGA) recognizes a benign proliferative lesion of the breast that can mimic adenocarcinoma histologically. We describe the fine-needle aspiration (FNA) biopsy cytology of MGA in two female patients. Smears were characterized by sparse cellularity, and the harvest consisted of a monotonous population of medium-sized cells, with vacuolated clear cytoplasm and round and uniform nuclei with small nucleoli. Clear cells appeared isolated or clustered with spindly fibroblasts. No naked nuclei of myoepithelial origin were present in the background. The differential diagnostic considerations included several breast lesions composed of clear cells. Subsequent surgical histology of lumpectomy revealed MGA. Further studies are needed to determine whether these cytologic features permit the specific identification of MGA, but our observations show that FNA is a sensitive method in recognizing the benign nature of the lesion. PMID- 8458289 TI - Fine-needle aspiration cytology of a pancreatic lymphoepithelial cyst. AB - Lymphoepithelial cyst of the pancreas (LECP) is an exceedingly rare nonneoplastic entity of uncertain histogenesis. A case of LECP clinically and radiographically mimicking a pseudocyst in a 44-yr-old man is described. Preoperative fine-needle aspiration cytology was instrumental in correctly identifying the lesion as a benign true cyst, thus permitting appropriate surgical management by local resection. The clinical and pathologic features of all ten previously reported cases of lymphoepithelial cyst of the pancreas are reviewed and current theories regarding its histogenesis are discussed. PMID- 8458290 TI - Cytology of allergic bronchopulmonary aspergillosis. AB - The cytologic features of a case of allergic bronchopulmonary aspergillosis (ABPA) are reported and the literature reviewed. The bronchial brushing smears in this case showed mucus that contained laminated aggregates of eosinophils with scattered Charcot-Leyden crystals and fungal hyphae. These cytologic findings, overlooked by the initial examining pathologist, reflected the "mucoid impaction of bronchi" component of ABPA and are therefore diagnostic of ABPA. A cytologic diagnosis of a clinically unsuspected ABPA would lead to the correct treatment and prevent unnecessary surgery. PMID- 8458291 TI - Skeletal structures that clinically simulate lymph nodes: encounters during fine needle aspiration. AB - We report eight patients in whom bones of the cervical spine or cervical ribs were clinically mistaken for jugular chain or supraclavicular lymphadenopathy, respectively. Each was referred for fine-needle aspiration by an experienced surgeon, oncologist, rheumatologist, or otolaryngologist. In the neck, the bony nature of the pseudo-lymph nodes was apparent when the needle contacted bone. Bone was not contacted by the needle in the supraclavicular fossa. Aspiration smears showed normal soft tissues in all cases. Radiographs showed cervical ribs in both of the patients with supraclavicular pseudo-lymphadenopathy. One of these was surgically explored and no adenopathy was detected. Radiographically, one patient with jugular chain findings had unilateral enlargement of a transverse vertebral bone process, another showed scoliosis, and a third had a normal cervical spine study. During follow-up of 1-33 mo (median = 14 mo), no patient developed adenopathy at any additional site. All are alive and well. PMID- 8458292 TI - Tubal metaplasia: a cytologic study with comparison to other neoplastic and non neoplastic conditions of the endocervix. AB - Tubal metaplasia of the endocervix (TME), a condition that may be confused morphologically with glandular neoplasia, is frequently found in cone or hysterectomy specimens. To determine the frequency of detecting TME in cytologic smears, we retrospectively reviewed 28 Papanicolaou (Pap) smears from 22 women (mean age 39.1 yr; range 25-60 yr) with histologically proven TME. Our criteria for TME were the presence of two cell types in addition to endocervical secretory cells, i.e., peg cells (cells with dark and granular cytoplasm and elongate nuclei) and ciliated cells. All women had cervical cytology specimens obtained with an endocervical brush shortly before the procedures in which TME was diagnosed, and five also had at least one post-procedure smear. Of 20 smears with an adequate, non-neoplastic endocervical component, TME was found in 2 (10%). In these two, TME cells constituted 10% and < 5% of all the glandular cells, respectively, and the percentage of ciliated cells in the TME was approximately 25% and 75%. In conclusion, TME was noted infrequently (10%) on the cervical cytosmears of women with histologically-proven TME. This result corresponds to the histologic finding that TME typically involves the upper endocervix and glandular epithelium, with only 13% of the women having TME on the surface of the lower endocervix. Atypical glandular cells on cervical cytology are a problem for clinicians and pathologists alike. The differential diagnosis of such atypia, including TME, cells of the lower uterine segment, squamous intraepithelial lesion in glands and glandular neoplasia, is discussed. PMID- 8458293 TI - "Educational guidelines for pre-existing diabetes complicated by pregnancy". AADE Task Force on Diabetes and Pregnancy. PMID- 8458294 TI - Using nontraditional methods to teach pediatric residents about insulin-dependent diabetes mellitus. AB - The purpose of this study was to examine the effect of a training experience on the attitudes and beliefs of pediatric residents concerning insulin-dependent diabetes mellitus (IDDM), persons with diabetes, and the use of a multidisciplinary team to empower patients/families. The resident training experience consisted of three days of diabetes lifestyle simulation including attending an educational program designed for newly-diagnosed patients and their families. Residents' attitudes, beliefs, and team function attitudes were measured at preinstruction, postinstruction, and 6 months following instruction. There was no significant change in beliefs about diabetes. Attitudes about persons with diabetes became more positive after the training experience, but did not continue after six months. Residents also expressed a change in team attitudes, specifically, in their acceptance of having the certified diabetes educator (CDE) nurse and the patient/family adjust insulin and manage insulin during illness. PMID- 8458295 TI - Diabetes self-care knowledge, behaviors, and metabolic control of older adults- the effect of a posteducational follow-up program. AB - Older adults with diabetes experience greater barriers to practicing self-care activities necessary for disease control than their younger counterparts. It was hypothesized that posteducational follow-up intervention would increase self-care knowledge scores, improve metabolic control, and reduce self-care behavioral deficits. Twenty-seven hospitalized elderly patients with diabetes who had completed an inpatient education program were recruited and randomized into experimental (n = 15) and control (n = 12) groups. A posttest on HbA1c and diabetes self-care knowledge (DKN) was administered to all subjects, and self care behavioral deficits were measured. A four-week follow-up intervention via telephone contact also was administered to the experimental subjects. No significant difference was observed in DKN and HbA1c values. A significant difference was achieved in reduction of self-care behavioral deficits (P < 0.05 0.01). It was concluded that posteducational follow-up is necessary for enhancing self-care adherence and ensuring safe practice of home care for elderly patients with diabetes. PMID- 8458296 TI - Assessing and implementing diabetes patient education programs for American Indian communities. AB - In many American Indian communities, the rate of diabetes has increased dramatically over the past 20 years. This health problem has become a major challenge for the Indian Health Service (IHS). The Diabetes Education Program of the IHS wanted to use the National Standards to promote the best quality diabetes education programs in all IHS and tribal facilities. However, the review criteria for the National Standards had to be adapted to fit the unique needs of the Indian communities. This paper describes the process used to evaluate and modify the review criteria to implement the National Standards within IHS health care facilities. PMID- 8458297 TI - Diabetic mothers and pregnancy loss: implications for diabetes educators. AB - Perinatal deaths among diabetic women are sufficiently common that nearly all diabetes educators eventually care for someone who loses a baby. This case report and discussion identifies ways in which diabetes educators can promote patients' health and provide emotional first aid in the immediate aftermath of perinatal loss. Psychological reactions of both the mother and the health care providers are considered. Practical ways to assist patients, and pitfalls to avoid, also are presented. PMID- 8458298 TI - Factors influencing diabetic clients' ability to read and comprehend printed diabetic diet material. AB - Factors related to diabetic clients' abilities to read and comprehend printed diabetic diet material were explored by collecting data on social and demographic variables, prior knowledge, reading ability (using the Nelson-Denny Test), and comprehension of the diet (using the cloze technique) from 58 outpatient diabetic clients. A mean estimated reading grade level of 8.9 was obtained for the printed material, based on the use of three readability formulas. Analysis of cloze scores revealed that 62% of the clients scored less than 40%, indicating that the material was too difficult for them to comprehend; 21% scored between 40% and 59%, suggesting the need for supplemental instruction; and 17% scored 60% or above, indicating ability to fully comprehend. Clients scoring less than 40% tended to be older and obtained lower scores on the Nelson-Denny, as compared with those in the highest cloze category. Results of a stepwise regression analysis indicated that the Nelson-Denny vocabulary score, client age, and duration of diabetes were the strongest predictor variables for comprehension of the diet material. PMID- 8458299 TI - Diabetes educators international: third time lucky? AB - Three attempts have been made to establish an international diabetes educators network (1984, 1988, 1991). This paper outlines the early meetings, and reports on the most recent 1991 initiative and the recommendations of three education workshops held during the International Diabetes Federation Congress (IDF) in Washington, DC, 1991. As a result of the workshops, a Steering Committee was formed to determine a structure and funding for an international diabetes educators network, to foster international networking, to establish communication with the IDF, and to plan another workshop during the 15th IDF Congress in Kobe, Japan. PMID- 8458300 TI - Report on the AADE survey for third-party reimbursement. PMID- 8458301 TI - Self-monitoring of blood glucose: an essential tool for the RD/CDE. PMID- 8458302 TI - Diabetes resource nurse: creating expertise in the primary nurse. PMID- 8458303 TI - Implications of clinical advancement systems and nurse case managers on the diabetes educator. PMID- 8458304 TI - Speaking out in gratitude. A message from your patients. PMID- 8458305 TI - Designing and implementing a comprehensive quality assurance program for bedside glucose testing. AB - A program for bedside glucose testing has been successfully implemented and in operation at Sharp Memorial Hospital since October 1990. The nursing staff training and certification process focuses on gaining an understanding of the issues and skills needed to routinely perform the tests to laboratory quality standards. Routine quality control checks are performed to ensure the accuracy and precision of the glucose values obtained on patients, thus maintaining quality in the process. Instituting this comprehensive QA program for bedside glucose testing has enabled us to improve the accuracy of our measurements and increase the quality of our patient care. PMID- 8458306 TI - Diabetes educators as cultural translators. PMID- 8458307 TI - Parental versus professional perceptions of obstacles to pediatric diabetes care. AB - Parents of children with insulin-dependent diabetes mellitus (IDDM) (n = 38) were surveyed to identify common and difficult obstacles to diabetes care. A list of these obstacles was cross-validated by a second parent sample (n = 47) who rated each item according to how common and difficult each item was for them. The list then was rated by a sample of diabetes professionals (n = 15) to evaluate the extent of agreement between parents and health care professionals regarding the frequency with which these obstacles occur and the difficulty they pose to everyday diabetes care. Professionals disagreed with parents regarding which obstacles were most common and difficult, generally rating problems as significantly more common and difficult (t = 5.20, P = < .001) than did the parents who experienced them. The results of the survey underscore the importance of health care providers evaluating the concerns of the local patient community when developing educational and treatment services for these patients. PMID- 8458308 TI - Reliability and validity of the Diabetes Family Behavior Scale (DFBS). AB - The Diabetes Family Behavior Scale (DFBS) was designed to measure diabetes specific family support. The purposes of this study were to refine the scale and to assess reliability and criterion validity in terms of relationship to metabolic control. The DFBS was administered to 321 children and adolescents with insulin-dependent diabetes mellitus (IDDM). Blood was drawn for determination of glycosylated hemoglobin (HbA1c). Based on an item-analysis procedure, the DFBS was revised to include 47 items with two subscales, one to reflect guidance control and one to reflect warmth-caring. Acceptable internal consistency was found for the DFBS total score (.86), and for the guidance-control (.81) and warmth-caring (.79) subscales. There was a statistically significant relationship in the expected direction between DFBS total score and HbA1c (r = -.12, P < .03), and between the guidance-control subscale and HbA1c (r = -.17, P < .002). PMID- 8458309 TI - The relationship between self-care and metabolic control in children with insulin dependent diabetes mellitus. AB - To assess the relationship between insulin-dependent diabetes mellitus (IDDM) self-care management and metabolic control in school-aged children, 21 children ages 10 to 14 years with a duration of IDDM of 5.5 years (range 1 to 13 years) were studied. Self-care was defined as the activities that children with IDDM initiate and perform on their own in the management of their disease. Self-care activity was assessed by a revised Self-Care Questionnaire (SCQ), and metabolic control was determined by HbA1c levels obtained at the same time the SCQ was completed. A higher level of self-care management (higher SCQ) was hypothesized to correlate with better metabolic control (lower HbA1c). Regression analysis of SCQ and HbA1c supported the expected inverse relationship but not at a significant level. The only significant predictors of self-care activity and metabolic control were experience at a specialized camp for children with diabetes and race, with Caucasian children scoring higher in self-care and having lower HbA1c values than African American children. PMID- 8458310 TI - Teaching assertive communication skills to adolescents with diabetes: evaluation of a camp curriculum. AB - Diabetes management requires consistently implementing adherence behaviors in a variety of settings. For some adolescents, consistency may be difficult due to problems in communication and assertiveness. The purpose of the present study was to evaluate the impact of a camp curriculum to teach assertive communication skills to adolescents with diabetes. The curriculum included didactic information, sharing of personal experiences, and role playing. Results showed a significant increase in adolescents' perceptions of their assertiveness from before to after the camp experience, an increase that was still apparent at a 3 month follow-up. No changes were reported in parental perceptions of their adolescents' degree of openness in communicating or in communication problems. In contrast, adolescents reported a significant decrease in their degree of openness in communicating with fathers, with a similar trend for mothers. These results suggest that the curriculum was successful in meeting the primary goal of enhancing the adolescents' assertive communication skills but had a questionable impact on their general communications with parents. PMID- 8458311 TI - Avoiding sugar: does research support traditional beliefs? PMID- 8458312 TI - Health care reform. PMID- 8458313 TI - Sterol balance studies in man. A critical review. PMID- 8458314 TI - The Kingston Project. II. The effects of high energy supplement and metronidazole on malnourished children rehabilitated in the community: anthropometry. AB - Malnourished children (mean age 1.2 years) referred from public health clinics to a paediatric metabolic ward in Kingston, Jamaica, were enrolled for treatment in a community-based health care project and were randomly allocated to one of two groups. The first group was treated at home with metronidazole and then for 6 months using the standard health care provided from local clinics by community health aides. The second group was given the same drug and home treatment, but in addition received a high energy supplement of 3.31 MJ daily for 3 months. We have previously shown a significant advantage in both weight and height gain for a group given the same supplement in contrast with standard health care controls (Heikens et al., 1989, Eur. J. Clin. Nutr. 43, 145-160), and in this study test the addition of a drug treatment aimed at reducing malabsorbtion due to a possible microbial overgrowth of the small bowel in malnourished children. This paper reports anthropometric findings showing significant benefits from both the drug and nutritional treatments. Greatest gains were by the group given both treatments, but the group given the antibiotic treatment, without energy supplementation, also made better growth recovery than did controls. Only 8% of the children treated with metronidazole failed to respond to community-based intervention and were admitted to hospital, compared with 19% for the other groups (P < 0.05). These findings support targetted high-energy supplementation for the rehabilitation of moderately malnourished children receiving health clinic care, and suggest further that such programs should include antibiotic treatment directed at SBBO. PMID- 8458316 TI - Serum cholesteryl ester fatty acids and their relation with serum lipids in elderly men in Crete and The Netherlands. AB - This study describes dietary fatty acid intake, as assessed from serum cholesteryl ester composition, and its relation to serum lipoprotein levels in 100 age-matched elderly men from Crete and Zutphen. All were survivors of the respective cohorts of the Seven Countries Study [Keys A (1980) Seven countries: a multivariate analysis of death and coronary heart disease. Cambridge, MA: Harvard University Press]. A significantly higher percentage of oleic acid and a significantly lower percentage of linoleic acid in the cholesteryl esters was observed in the Cretan compared with the Zutphen men. The mean serum total cholesterol levels of the elderly men in Crete and Zutphen were similar (5.98 and 5.92 mmol/l, respectively), but in the Cretans the HDL cholesterol level was significantly higher (1.28 vs 1.09 mmol/l). The percentage of smokers and the average body mass index did not differ between the Cretan and Zutphen men, but the percentage of severely overweight men was three times higher in the Cretan cohort. Among men in Zutphen the oleic acid content of the cholesteryl esters was positively associated with the HDL cholesterol level, independent of the effects of age, body mass index, cigarette smoking and alcohol intake. However, the difference in HDL cholesterol level between Zutphen and Crete could be explained to only a minor extent by differences in serum cholesteryl oleic acid, smoking, or obesity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458315 TI - The Kingston Project. III. The effects of high energy supplement and metronidazole on malnourished children rehabilitated in the community: morbidity and growth. AB - In the Kingston Project malnourished children referred from public health clinics to a metabolic ward were treated at home using community health aides within the existing health service. We have previously provided anthropometric results showing significantly greater gains in weight and length for groups given a high energy supplement (3.31 MJ daily) for 3 months during treatment, and greatest gains for a group treated with metronidazole at the beginning of supplementation [Heikens et al., Eur. J. Clin. Nutr. 43, 145-160 (1989); 47, 160-173 (1993)]. We now present findings on morbidity and relate these to the separate interventions and to growth velocities. Although referral was solely on nutritional criteria, 65% of the sample were found to have additional illnesses at enrollment. During the study period (6 months) upper respiratory tract infections (URTI) were the commonest illness in all groups; there were significantly more gastroenteric infections in the group given the supplement, but not the antibiotic, treatment; the children who received only the standard health service care were ill more often and for longer periods than children in the other groups. Diarrhoea, fever and dysentery prevalences were all found to relate significantly to weight velocity, and although prevalences differed between treatment groups, the detrimental effect on velocity was similar whichever the group. PMID- 8458317 TI - Vitamin K in breast milk: no influence of maternal dietary intake. AB - There is limited information available on the vitamin K intake of lactating mothers, concentration of vitamin K1 in breast milk, and the effect of long-term vitamin K1 supplementation of lactating mothers on the vitamin K1 concentration in breast milk. In a randomized study, we followed 20 mothers who received a daily oral vitamin K1 supplement (average 88 micrograms, supplemented group) and 16 mothers receiving no supplement (control group) from 4 throughout 91 days postpartum. Maternal vitamin K intakes (weighed dietary intake) at 4-6, 25-29 and 87-91 days postpartum ranged between 73 and 1735 micrograms/day. Differences between the groups were statistically not significant. Average intake exceeded the recommended dietary intake for lactating women of 55 micrograms/day by 670%. In the supplemented group, mean breast-milk vitamin K1 concentrations (HPLC) at 5, 26 and 88 days postpartum were 1.73 (SD 0.74), 1.36 (SD 0.81) and 1.67 (SD 2.01) ng/ml, respectively. Corresponding values in the control group were 1.44 (SD 0.57), 1.68 (SD 0.70) and 1.78 (SD 1.05) ng/ml. The latter were not statistically different from values in the supplemented group. Mean daily vitamin K1 intakes of infants breast-fed by supplemented mothers were 0.69 (SD 0.42), 0.93 (SD 0.51) and 1.25 (1.53) micrograms, respectively on days 5, 26 and 88. Corresponding values in the control group were 0.69 (SD 0.30), 1.07 (SD 0.58) and 1.31 (SD 0.95) micrograms and were statistically not different from values in the supplemented group. Average vitamin K1 intakes corresponded to 7-13% of the recommended dietary intake of 10 micrograms/d for infants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458318 TI - Evaluation of dual energy X-ray absorptiometry as a method of measurement of body fat. AB - Two densitometers, the Hologic QDR 1000W densitometer (QDR) and the Lunar DPX densitometer (DPX), were compared with four traditional methods for the measurement of body fat: underwater weighing (UWW), skinfold thickness measurements (SKM), bioelectrical impedance analysis (BIA) and deuterium oxide dilution (D2O). Precision was assessed by conducting 10 repeated observations on one subject using QDR: the coefficient of variability (CV) was 1.8% for percentage fat, 0.6% for lean mass and 2.1% for fat mass. In 10 repeated observations on three subjects, QDR CV was greater than UWW (CV percentage fat QDR 1.3% (range 0.9-1.6%) compared with 4.8% (range 3.8-6.6%) for percentage fat UWW). Based on observations of 12 subjects, correlations of QDR and DPX with UWW for percentage fat were high: Pearson's r = 0.916, P < 0.0001 for QDR and r = 0.913, P < 0.00001 for DPX. A limits of agreement estimate showed a between method difference of +1.3% (range -4% to +7%) for QDR compared with UWW. The DPX showed a between-method difference of +4.8% (range +2% to +9%) compared with UWW. The correlation of the two DEXAs was high (r = 0.986, P < 0.0001). Correlations between both DEXA instruments and other methods were high (for QDR: r = 0.824, P < 0.001 for SKM; r = 0.972, P < 0.0001 for BIA; r = 0.787, P < 0.002 for D2O; for DPX: r = 0.923, P < 0.00001 for SKM; r = 0.910, P < 0.00001 for BIA; r = 0.812, P < 0.001 for D2O). It was concluded that QDR and DPX measured percentage fat with greater precision than UWW as reflected by the CV and correlated with other methods. Predicted percentage fat measurements using QDR would be 3% lower than DPX, but both DEXAs predict percentage fat 1.3-4.8% higher than UWW. In addition, the DEXA technique has the unique ability to produce precise regional measurements (for each arm, each leg, the head and the trunk) of bone mineral content (BMC), fat mass (FAT), lean mass (LEAN) and percentage fat. PMID- 8458319 TI - Interactions of the p107 and Rb proteins with E2F during the cell proliferation response. AB - The E2F transcription factor is found in complexes with a variety of cellular proteins including the retinoblastoma tumor suppressor protein. Various assays have demonstrated a tight correlation between the functional capacity of Rb as a growth suppressor and its ability to bind to E2F. Moreover, only the underphosphorylated form of Rb, which appears to be the active species, interacts with E2F. Despite the fact that the majority of Rb becomes hyperphosphorylated at the end of G1, we now show that the E2F-Rb interaction persists through the G1/S transition and into S phase. A distinct E2F complex does appear to be regulated in relation to the transition from G1 to S phase. We now demonstrate that this complex contains the Rb-related p107 protein. Moreover, like the Rb protein, p107 inhibits E2F-dependent transcription in a co-transfection assay. This result, together with the observation that free, uncomplexed E2F accumulates as cells leave G1 and enter S phase, suggests that the p107 protein may regulate E2F dependent transcription during G1. In contrast, although Rb does regulate the transcriptional activity of E2F, this association does not coincide with the G1 to S phase transition. PMID- 8458320 TI - Wild-type p53 adopts a 'mutant'-like conformation when bound to DNA. AB - p53 is a negative regulator of cell growth. The majority of human tumors express mutant p53 proteins, which can be distinguished from wild-type by their immuno reactivity to a panel of conformation-specific monoclonal antibodies, such as PAb421, PAb1620 and PAb246. Wild-type p53 has sequence-specific DNA binding activity. We demonstrate that upon binding DNA wild-type p53 changes conformation at both its N- and C-termini, such that it adopts a 'mutant'-like conformation. Very few of the known DNA binding proteins exhibit long-range conformational changes upon binding to DNA. Such proteins, like the Drosophila heat shock transcription factor, have DNA binding domains whose activity is regulated by conformation. The DNA binding activity, and therefore the function, of wild-type p53 may be regulated via its ability to adopt distinct conformations. PMID- 8458321 TI - The transforming and suppressor functions of p53 alleles: effects of mutations that disrupt phosphorylation, oligomerization and nuclear translocation. AB - Mutant p53 alleles that have a recessive phenotype in human tumors can, in cooperation with an activated H-ras gene, transform rat embryo fibroblasts (REFs). Mutant p53 proteins differ from wild type, and from each other in conformation, localization and transforming potential. Missense mutations in codons 143, 175 and 275 confer strong transforming potential. A serine 135 p53 mutant has an intermediate transforming potential, while the histidine codon 273 allele transforms weakly, if at all. In contrast to the wild type p53 gene, mutant p53 alleles with strong transforming ability cannot suppress the transformation of REFs by other oncogenes. The His273 allele retains partial suppressor function in this assay. The relevance of p53 oligomerization, phosphorylation and nuclear translocation to the transforming potential of mutant p53 and to wild type p53 suppressor function were examined. The inability of mutant p53 polypeptides to form homodimers correlates with loss of transforming function. Monomeric variants of wild type p53 protein, however, retain the ability to suppress focus formation. Phosphorylation of serine residues 315 and 392 is not required for the transforming function of mutant p53, nor is serine 315 required for suppressor function when these alleles are constitutively expressed in REF assays. Nuclear translocation-defective mutant and wild type p53 proteins retain transforming and suppressor function in REF assays. PMID- 8458322 TI - The Escherichia coli nucleoid protein H-NS functions directly as a transcriptional repressor. AB - The H-NS protein is a major constituent of the Escherichia coli nucleoid structure and is implicated in the compact organization of the chromosome. Based on recent genetic evidence, this protein appears to influence the transcription of a variety of apparently unlinked genes on the chromosome, although the underlying molecular mechanism is not fully understood. In this study, we carried out a series of in vitro transcription assays including purified H-NS with special reference to the osmotically inducible proV promoter of the proVWX operon (or proU), whose expression is known to be derepressed by lesions of the hns (osmZ) gene. Here, H-NS was revealed to selectively inhibit an early step(s) of proV transcription initiation through its direct binding to the promoter region. It was thus demonstrated that H-NS functions directly as a transcriptional repressor. Under the in vitro conditions used, this in vitro inhibitory effect of H-NS was affected by changes in the superhelical density of template DNAs and more significantly by the concentration of potassium (K+) ions. These results are also discussed with regard to the mechanism underlying regulation of the proV promoter in response to the medium osmolarity. PMID- 8458323 TI - Visualization of focal sites of transcription within human nuclei. AB - HeLa cells were encapsulated in agarose microbeads, permeabilized and incubated with Br-UTP in a 'physiological' buffer; then sites of RNA synthesis were immunolabelled using an antibody that reacts with Br-RNA. After extending nascent RNA chains by < 400 nucleotides in vitro, approximately 300-500 focal synthetic sites can be seen in each nucleus by fluorescence microscopy. Most foci also contain a component of the splicing apparatus detected by an anti-Sm antibody. alpha-amanitin, an inhibitor of RNA polymerase II, prevents incorporation into these foci; then, using a slightly higher salt concentration, approximately 25 nucleolar foci became clearly visible. Both nucleolar and extra-nucleolar foci remain after nucleolytic removal of approximately 90% chromatin. An underlying structure probably organizes groups of transcription units into 'factories' where transcripts are both synthesized and processed. PMID- 8458324 TI - Stably maintained microdomain of localized unrestrained supercoiling at a Drosophila heat shock gene locus. AB - A psoralen crosslinking assay was utilized to detect localized, unrestrained DNA supercoiling (torsional tension) in vivo in Drosophila chromosomal regions subject to differential transcriptional activity. By comparing rates of crosslinking in intact cells with those in cells where potential tension in chromosomal domains was relaxed by DNA strand nicking, the contribution to psoralen accessibility caused by altered DNA-protein interactions (e.g. nucleosomal perturbations) was distinguished from that due to the presence of unrestrained supercoiling in a region of interest. The heat shock protein 70 (hsp70) genes were wound with a significant level of superhelical tension that remained virtually unaltered whether or not the genes were transcriptionally activated by thermal elevation. Constitutively expressed 18S ribosomal RNA genes also exhibited unrestrained superhelical tension at a level comparable with that across hsp70. In contrast, flanking regions downstream of each of the divergent hsp70 genes at locus 87A7 exhibited substantially less tension. Thus the results point to the existence of stable, torsionally stressed topological domains within eukaryotic chromosomal DNA, suggesting that the relaxing action of topoisomerases is not ubiquitous throughout the nucleus but, in fact, is likely to be tightly regulated. PMID- 8458325 TI - The minimal requirements for activity in transgenic mice of hypersensitive site 3 of the beta globin locus control region. AB - Proper expression of the human beta-like globin genes is completely dependent on the presence of the locus control region or LCR, a region containing four DNase hypersensitive sites (HS1-4) situated 5' to the structural genes. Linkage of the LCR to a transgene results in copy number-dependent transcription, independent of the site of integration in the host genome. We have analysed a small region of the LCR (HS3) in transgenic animals to determine the minimal interactions that are required for this property. The results show that a specific combination of a G-rich sequence flanked on each side by one binding site for the transcription factor GATA1 is essential to obtain position-independent expression of a linked beta globin gene in erythroid cells. The overall transcriptional activity of HS3 is achieved through synergy with other combinations of similar binding sites. PMID- 8458326 TI - The expression and role of a proneural gene, achaete, in the development of the larval nervous system of Drosophila. AB - The proneural genes of Drosophila are required for the segregation of neural precursors from the ectoderm. One of the proneural genes, achaete (ac), is responsible for the formation of a subset of larval and adult sense organs. We have examined the pattern of expression of ac and its regulation during embryogenesis. ac is expressed at particular locations of the ectoderm according to a highly dynamic and complex pattern. At each location the expression of ac occurs in two stages. First, ac is expressed in a cluster of cells ('competent' stage). This pattern of expression depends on an array of cis-regulatory sites which promote the expression of ac in clusters of cells at particular locations. Second, one cell of each cluster accumulates ac transcripts at a high level ('determined' stage) and becomes the neural progenitor cell. The restriction of the determined stage to one cell of the cluster requires the gene Notch. The transactivation of ac by sc (scute) or by other genes of the achaete-scute complex (AS-C) plays no role in defining the initial pattern of expression of ac, but might play a role in the shift from the competent to the determined level. We propose that the requirements of particular sense organs for different AS-C genes reflect the organization of this gene complex, rather than functional differences between the genes. PMID- 8458327 TI - Analysis of gene expression in mouse preimplantation embryos demonstrates that the primary role of enhancers is to relieve repression of promoters. AB - Enhancers are generally viewed simply as extensions of promoters, lacking a function of their own. However, previous studies of mouse preimplantation embryos revealed that 1-cell embryos can utilize enhancer-responsive promoters efficiently without an enhancer, whereas 2-cell embryos require an enhancer to achieve the same levels of expression. This suggested that enhancers relieved a repression in 2-cell embryos that is absent in 1-cell embryos. Results presented here demonstrate first that the ability of 1-cell embryos to dispense with enhancers does not result from the absence of specific activation proteins. Under conditions where GAL4-VP16 activated a GAL4-dependent promoter in both embryos, GAL4-VP16 activated a GAL4-dependent enhancer only in 2-cell embryos. Moreover, the role of an enhancer is not to compensate for either changes in promoter requirements, or for reduced levels of promoter-specific transcription factors. Linker-scanning mutations in a natural promoter revealed that both embryos utilized the same promoter elements, and comparison of different promoters revealed that these embryos have equivalent transcriptional capacities. In addition, titration experiments revealed less Sp1 activity in 1-cell embryos where enhancers are dispensable than in 2-cell embryos where enhancers are required. Therefore, we propose that the primary function of enhancers, first evident with formation of a mouse 2-cell embryo, is to prevent repression of weak promoters, probably by altering chromatin structure. Consistent with this hypothesis is the fact that butyrate, an agent that alters chromatin structure, stimulated promoters in 2-cell embryos, but not in 1-cell embryos. PMID- 8458328 TI - Modulation of transcriptional activation by ligand-dependent phosphorylation of the human oestrogen receptor A/B region. AB - Using a transient co-transfection system, we show that the human oestrogen receptor (hER) becomes phosphorylated in the presence of oestradiol (E2) as well as in the presence of the anti-oestrogens 4-hydroxy-tamoxifen (OHT) and ICI 164, 384 (ICI), although at lower efficiencies than with E2. There are multiple sites of phosphorylation in hER; using deletion and point mutants one of these sites has been mapped in the N-terminal A/B region at serine 118. Mutation of this serine to alanine caused, in a number of cell types, a significant reduction in transcriptional activation by hER from reporter genes containing an oestrogen response element (ERE), but did not affect the DNA binding properties or nuclear localization of hER. Thus phosphorylation of serine 118 is important for the action of the transcription activation function 1 (AF-1) located in the A/B region of the oestrogen receptor. PMID- 8458329 TI - Synergistic activation of the HTLV1 LTR Ets-responsive region by transcription factors Ets1 and Sp1. AB - Ets1 is the prototype of a family of transcriptional activators whose activity depends on the binding to specific DNA sequences characterized by an invariant GGA core sequence. We have previously demonstrated that transcriptional activation by Ets1 of the long terminal repeat (LTR) of human T cell lymphotropic virus type 1 is strictly dependent on the binding of Ets1 to two sites, ERE-A and ERE-B, localized in a 44 bp long Ets-responsive region (ERR1). We report here that the activity of ERR1 as an efficient Ets1 response element in HeLa cells also depends on the integrity of an Sp1 binding site localized immediately upstream of ERE-A. The response to Ets1 of an element restricted to the SP1/ERE-A binding sites is also strictly dependent on both the Ets1 and Sp1 binding sites. In vitro, Sp1 and Ets1 are shown to cooperate to form a ternary complex with the SP1/ERE-A element. Reconstitution experiments in Drosophila melanogaster Schneider cells show that Ets1 and Sp1 act synergistically to activate transcription from either the ERR1 or the SP1/ERE-A elements and that synergy requires the binding of both Sp1 and Ets1 to their cognate sites. SP1/ERE-A elements are found in the enhancer/promoter region of several cellular genes, suggesting that synergy between Ets1 and Sp1 is not restricted to the ERR1 region of the HTLV1 LTR. These results strengthen the notion that Ets1 as well as other members of the Ets family usually function as components of larger transcription complexes to regulate the activity of a variety of viral and cellular genes. PMID- 8458330 TI - The functional versatility of CREM is determined by its modular structure. AB - The CREM gene (cAMP-responsive element modulator) generates both activators and repressors of cAMP-induced transcription by alternative splicing. We determined the exon structure of the CREM gene and have identified new isoforms. We show that CREM isoforms with different structural characteristics are generated by the shuffling of exons to produce proteins with various combinations of functional domains. CREM proteins bind efficiently to CREs and here we demonstrate that the various isoforms heterodimerize in vivo with each other and with CREB. The two alternative DNA binding domains of CREM, which are differentially spliced in the various isoforms, show distinct binding efficiencies, while CREM alpha/CREB heterodimers exhibit stronger binding than CREM beta/CREB heterodimers to a consensus CRE in vitro. We identify the protein domains involved in activation function and find that the phosphorylation domain and a single glutamine-rich domain are sufficient for activation. A minimal CREM repressor, containing only the b-Zip motif, efficiently antagonizes cAMP-induced transcription. In addition, phosphorylation may reduce repressor function, as a CREM beta mutant carrying a mutation of the serine phosphoacceptor site (CREM beta 68) represses more efficiently than the wild-type CREM beta. PMID- 8458331 TI - Identification of three residues in the basic regions of the bZIP proteins GCN4, C/EBP and TAF-1 that are involved in specific DNA binding. AB - The bZIP regions of the eukaryotic transcription factors GCN4 and C/EBP have similar protein sequences but they recognize different DNA sequences. In order to understand their specificity, a vector was constructed which permits overexpression in Escherichia coli of those domains of GCN4 that are necessary and sufficient for specific DNA binding i.e. the basic region and the leucine zipper. Specific DNA binding was monitored with gel shift experiments. The residues of the basic region of GCN4 were systematically replaced by those of C/EBP to transform GCN4 into C/EBP with respect to DNA binding. Residues -17, -16 and -14 were found to be responsible for switching GCN4 to C/EBP binding specificity (we define as residue +1 the first leucine of the first leucine heptad repeat of GCN4). We broadened the specificity of GCN4 to TAF-1 by replacing residues -15 and -17 and we changed the specificity of C/EBP to TAF-1 by swapping residue -17 of a particular hybrid. Thus residues positioned from -14 to -17 of the basic region play a key role in recognizing specific DNA sequences. PMID- 8458332 TI - The CAGTCACA box in the fission yeast Schizosaccharomyces pombe functions like a TATA element and binds a novel factor. AB - Fourteen ribosomal protein genes from the fission yeast Schizosaccharomyces pombe contain a highly conserved sequence, CAGTCACA, in the proximal promoter. This sequence, which was also conserved in its location, was found where the TATA element usually resides. Deletion and point mutations in the CAGTCACA box reduced the expression of these genes to almost zero and caused aberrant transcriptional start sites. Insertions between this box and the original transcriptional start sites led to new start sites which were the same distance from the CAGTCACA box as the original start sites. The results presented provide evidence that this box, like a TATA sequence, is involved in basal expression and fixing the transcriptional start sites of these genes. Furthermore, the CAGTCACA sequence is the target of a binding protein which appears to be different from the TATA binding protein. PMID- 8458333 TI - Evidence for an interaction between the CYP1(HAP1) activator and a cellular factor during heme-dependent transcriptional regulation in the yeast Saccharomyces cerevisiae. AB - Previously, it was shown that the CYP1(HAP1) gene product mediates the transcription of several oxygen-regulated genes through a metabolic co-effector, heme, in the yeast Saccharomyces cerevisiae. This study investigates the overproduction of the CYP1 protein when the CYP1(HAP1) gene is placed under the control of the GAL10-CYC1 hybrid promoter (either at the locus of the CYP1(HAP1) gene or cloned in a high-copy-number plasmid). In these conditions, the CYP1 protein is detected by Western blot analysis and has a molecular mass in agreement with the open reading frame sequence. Band-shift experiments show that the CYP1(HAP1) protein is able to interact specifically with its target sequences in vitro without addition of hemin, and forms a large complex with one or several unidentified factors denoted as X. Addition of hemin allows the formation of a new complex which has a lower molecular mass. The internal deletion of the seven repeated amino acid sequences containing the KCPVDH motif in the CYP1(HAP1) protein modifies the heme responsiveness phenomenon observed in vitro in the band shift experiments and in vivo in the transcription of the CYB2, CYC1, CYP3(CYC7) and ERG11 genes. On the basis of these data, we propose a new model for heme induced activation of the CYP1 protein. PMID- 8458334 TI - Discrete sequence elements control posterior pole accumulation and translational repression of maternal cyclin B RNA in Drosophila. AB - The concentration of cyclin B transcripts at the posterior pole of the Drosophila oocyte occurs at a late stage of oogenesis and is dependent on the sequence in the 3' untranslated part of the RNA. These transcripts become incorporated into the pole cells of the developing embryo and persist through a subsequent period of embryogenesis in which these cells are not dividing. We show that RNA injected into the posterior cytoplasm of syncytial embryos accumulates in the pole cells if it contains sequences present in the 3' untranslated region of maternal cyclin B transcripts. The injected RNA is not translated until a point prior to the resumption of mitosis by these cells, once they have become incorporated into the gonads. Zygotic transcription directed from the cyclin B promoter does not begin in the pole cells until the first instar larva has hatched. Deletion of a small sequence element from the 3' untranslated region of an epitope tagged cyclin B RNA does not affect its posterior accumulation but results in its premature translation. PMID- 8458335 TI - The low abundance of U7 snRNA is partly determined by its Sm binding site. AB - In transient expression studies after DNA transfection of HeLa cells, the mouse U7 gene produces only approximately 30% of the RNA produced by a mouse U1b gene. This difference persists even when the transfected genes have all their 5' and 3' flanking sequences exchanged suggesting a post-transcriptional effect. When the special U7 Sm binding site is mutated to a consensus derived from the major snRNAs (Sm-opt), the U7 RNA level increases 4- to 5-fold, whereas no RNA is detected from a U7 gene with a non-functional Sm binding site (Sm-mut). Moreover, U1b genes with the U7 Sm binding site yield reduced RNA levels. The Sm-opt site also alters the cellular behaviour of the corresponding U7 snRNA. It accumulates to a higher level in the nucleus than wild type U7 RNA, and is better immunoprecipitable with anti-Sm antibodies. Injection experiments in Xenopus oocytes indicate that the U7 genes with either Sm-opt or Sm-mut sites produce similar amounts of RNA as wild type U7, but that they differ in opposing ways in the processing of precursors to mature size U7 snRNA and in nuclear accumulation. However, in reconstitution experiments using Xenopus oocytes, we show that U7 Sm opt RNA, despite its efficient nuclear accumulation, is not active in 3' processing of histone pre-mRNA, whereas wild type U7 RNA is assembled into functional snRNPs, which correctly process histone pre-mRNA substrate. This suggests a functional importance of the special U7 Sm sequence. PMID- 8458336 TI - The trans-spliceosomal U2 snRNP protein 40K of Trypanosoma brucei: cloning and analysis of functional domains reveals homology to a mammalian snRNP protein. AB - Through immunoscreening we have isolated a cDNA encoding the trans-spliceosomal U2 snRNP-specific 40 kDa protein of Trypanosoma brucei. The protein has a predicted molecular weight of 36.6 kDa and shows 31% amino acid identity with the human U2 snRNP A' protein of 28.4 kDa. The homology between the trypanosome and human protein sequences is restricted to the N-terminal half where they share a series of six leucine repeat motifs. Sequence alignment revealed three 40K specific regions: a C-terminal extension and two insertions, one of which makes up a seventh leucine repeat. Bacterially expressed 40K protein efficiently bound RNA by itself in a nonspecific manner; this general RNA binding activity was located to a region in the C-terminal half overlapping with the leucine repeat domain. U2 RNA-specific interaction required the presence of other trypanosome proteins and depended upon the loop IV sequence of U2 RNA. Deletion analysis of the 40K protein demonstrated the leucine repeats, including the 40K-specific, seventh repeat, to be essential for specific U2 RNP assembly, most likely through their role as an interface for protein-protein interaction. PMID- 8458337 TI - Conversion of a trans-spliced C. elegans gene into a conventional gene by introduction of a splice donor site. AB - In Caenorhabditis elegans, pre-mRNAs that are trans-spliced are distinguished by the presence of an 'outron', intron-like RNA at the 5' end followed by a splice acceptor. We report that trans-splicing of the rol-6 gene can be completely suppressed simply by introducing a donor site into its 173 nt outron, at a site 50 nt upstream of the trans-splice site, thereby converting rol-6 into a conventional gene with a spliced intron near its 5' end. When the consensus donor site was inserted at sites further upstream it was less effective in replacing transplicing with cis-splicing. Surprisingly, the length of the intron was not the important variable, since lengthening of the 50 nt intron to 250 nt did not restore trans-splicing. Apparently the context into which the splice site was introduced determined the efficiency of its use. These results support the conclusion that the sole signal for trans-splicing is the presence of an outron. Clearly, cis- and trans-splice acceptor sites are interchangeable, allowing the possibility of competition between the two types of splicing. PMID- 8458338 TI - In vivo inhibition of duck hepatitis B virus replication and gene expression by phosphorothioate modified antisense oligodeoxynucleotides. AB - Antisense oligodeoxynucleotide strategies have been employed in a variety of eukaryotic systems both to understand normal gene function and to block gene expression. Pharmacologically, 'code blockers' are ideal agents for antitumour and antimicrobial treatments because of their specific mode of action. Here we report the inhibition of duck hepatitis B virus (DHBV) by antisense oligodeoxynucleotides in primary duck hepatocyte cultures in vitro as well as in DHBV-infected Pekin ducks in vivo. The most effective antisense oligodeoxynucleotide was directed against the 5' region of the pre-S gene and resulted in a complete inhibition of viral replication and gene expression in vitro and in vivo. These results demonstrate the application of antisense oligodeoxynucleotides in vivo and exemplify their potential as human antiviral therapeutics. PMID- 8458339 TI - Gene targeting in the Ig kappa locus: efficient generation of lambda chain expressing B cells, independent of gene rearrangements in Ig kappa. AB - The production of lambda chain-expressing B cells was studied in mice in which either the gene encoding the constant region of the kappa chain (C kappa) or the intron enhancer in the Ig kappa locus was inactivated by insertion of a neomycin resistance gene. The two mutants have similar phenotypes: in heterozygous mutant mice the fraction of lambda chain-bearing B cells is twice that in the wildtype. Homozygous mutants produce approximately 7 times more lambda-expressing B cells (and about 2.3 times fewer total B cells) in the bone marrow than their normal counterparts, suggesting that B cell progenitors can differentiate into either kappa- or lambda-producing cells and do the latter in the mutants. Whereas gene rearrangements in the Ig kappa locus are blocked in the case of enhancer inactivation, they still occur in that of the C kappa mutant, although in this mutant RS rearrangement is lower than in the wildtype. This indicates that gene rearrangements in the Ig lambda locus can occur in the absence of a putative positive signal resulting from gene rearrangements in Ig kappa, including RS recombination. Complementing these results, we also present data indicating that in normal B cell development kappa chain rearrangement can be preceded by lambda chain rearrangement and that the frequency of kappa/lambda double producers is small and insufficient to explain the massive production of lambda chain expressing B cells in the mutants. PMID- 8458340 TI - B cell development in mice that lack one or both immunoglobulin kappa light chain genes. AB - We have generated mice that lack the ability to produce immunoglobulin (Ig) kappa light chains by targeted deletion of J kappa and C kappa gene segments and the intervening sequences in mouse embryonic stem cells. In wild type mice, approximately 95% of B cells express kappa light chains and only approximately 5% express lambda light chains. Mice heterozygous for the J kappa C kappa deletion have approximately 2-fold more lambda+ B cells than wild-type littermates. Compared with normal mice, homozygous mutants for the J kappa C kappa deletion have about half the number of B cells in both the newly generated and the peripheral B cell compartments, and all of these B cells express lambda light chains in their Ig. Therefore, homozygous mutant mice appear to produce lambda expressing cells at nearly 10 times the rate observed in normal mice. These findings demonstrate that kappa gene assembly and/or expression is not a prerequisite for lambda gene assembly and expression. Furthermore, there is no detectable rearrangement of 3' kappa RS sequences in lambda+ B cells of the homozygous mutant mice, thus rearrangements of these sequences, per se, is not required for lambda light chain gene assembly. We discuss these findings in the context of their implications for the control of Ig light chain gene rearrangement and potential applications of the mutant animals. PMID- 8458341 TI - How a sex pheromone might act at a concentration below 10(-16) M. AB - The sex-inducing pheromone of Volvox carteri is a glycoprotein that triggers development of males and females at a concentration below 10(-16) M. Evidence is presented for the existence of a novel mechanism of signal amplification operating within the extracellular matrix of this multicellular organism. A family of 70 kDa matrix glycoproteins denoted pherophorins bear a C-terminal domain being homologous to the sex-inducing pheromone. Under the influence of the pheromone, this domain is liberated by highly specific proteolysis. PMID- 8458342 TI - OB(oligonucleotide/oligosaccharide binding)-fold: common structural and functional solution for non-homologous sequences. AB - A novel folding motif has been observed in four different proteins which bind oligonucleotides or oligosaccharides: staphylococcal nuclease, anticodon binding domain of asp-tRNA synthetase and B-subunits of heat-labile enterotoxin and verotoxin-1. The common fold of the four proteins, which we call the OB-fold, has a five-stranded beta-sheet coiled to form a closed beta-barrel. This barrel is capped by an alpha-helix located between the third and fourth strands. The barrel helix frameworks can be superimposed with r.m.s. deviations of 1.4-2.2 A, but no similarities can be observed in the corresponding alignment of the four sequences. The nucleotide or sugar binding sites, known for three of the four proteins, are located in nearly the same position in each protein: on the side surface of the beta-barrel, where three loops come together. Here we describe the determinants of the OB-fold, based on an analysis of all four structures. These proposed determinants explain how very different sequences adopt the OB-fold. They also suggest a reinterpretation of the controversial structure of gene 5 ssDNA binding protein, which exhibits some topological and functional similarities with the OB-fold proteins. PMID- 8458343 TI - Brefeldin A reversibly blocks early but not late protein transport steps in the yeast secretory pathway. AB - We have found that brefeldin A (BFA) inhibited the growth of an ise1 mutant of Saccharomyces cerevisiae. Genetic complementation and mapping studies demonstrated that ise1 was allelic to erg6, a gene required for the biosynthesis of the principal membrane sterol of yeast, ergosterol. Treatment of ise1 cells with BFA resulted in an immediate block in protein transport through the secretory pathway. Vacuolar carboxypeptidase Y (CPY) and the secreted pheromone alpha-factor accumulated as both the core glycosylated (ER) and alpha 1,6 mannosylated (early Golgi) forms in drug-treated cells. The modification of alpha factor with alpha 1,6 mannose in BFA-treated cells did not appear to result from retrograde transport of the alpha 1,6 mannosyl-transferase into the ER. We found that transport of CPY from medial and late Golgi compartments to the vacuole was unaffected by BFA, nor was secretion of alpha 1,3 mannosylated alpha-factor or invertase blocked by BFA. The effects of BFA on the secretory pathway were also reversible after brief exposure (< 40 min) to the drug. We suggest that the primary effect of BFA in S. cerevisiae is restricted to the ER and the alpha 1,6 mannosyltransferase compartment of the Golgi complex. PMID- 8458344 TI - A signal sequence is not required for protein export in prlA mutants of Escherichia coli. AB - The prlA/secY gene, which codes for an integral membrane protein component of the Escherichia coli protein export machinery, is the locus of the strongest suppressors of signal sequence mutations. We demonstrate that two exported proteins of E.coli, maltose-binding protein and alkaline phosphatase, each lacking its entire signal sequence, are exported to the periplasm in several prlA mutants. The export efficiency can be substantial; in a strain carrying the prlA4 allele, 30% of signal-sequenceless alkaline phosphatase is exported to the periplasm. Other components of the E.coli export machinery, including SecA, are required for this export. SecB is required for the export of signal-sequenceless alkaline phosphatase even though the normal export of alkaline phosphatase does not require this chaperonin. Our findings indicate that signal sequences confer speed and efficiency upon the export process, but that they are not always essential for export. Entry into the export pathway may involve components that so overlap in function that the absence of a signal sequence can be compensated for, or there may exist one or more means of entry that do not require signal sequences at all. PMID- 8458345 TI - A chimeric toxin to study the role of the 21 kDa GTP binding protein rho in the control of actin microfilament assembly. AB - We have developed a new tool for studying the role of rho in actin stress fibre formation. Clostridium botulinum exoenzyme C3 which affects actin microfilament assembly by ADP-ribosylation of p21 rho was genetically fused in various ways to diphtheria toxin (DT). The resulting chimeric toxins were tested on Vero cells. Chimeras of C3 and both the A and B fragments of diphtheria toxin had reduced cell binding activities but were apparently able to penetrate into Vero cells by the same mechanism as DT. Upon exposure to low pH, DC3B, a fusion protein of C3 and DT B fragment, had a high affinity for the DT receptor, but was apparently not able to translocate to the cytosol upon acidification. In spite of this, addition of picomolar concentrations of DC3B to the growth medium caused disruption of the cell microfilament system associated with vinculin and blocked cell growth efficiently, indicating that the C3 part of DC3B reached the cytosol, albeit by a different mechanism than that of whole diphtheria toxin. The chimeric DC3B toxin was also applied to Vero cells infected by Listeria monocytogenes, a pathogenic bacterium that uses an unknown mechanism of actin polymerization to move rapidly in the cytosol. DC3B inhibited the bacterially induced microfilament assembly indicating that L. monocytogenes utilizes a cellular rho dependent mechanism in this process. PMID- 8458346 TI - The estrogen receptor cooperates with the TGF alpha receptor (c-erbB) in regulation of chicken erythroid progenitor self-renewal. AB - A unique combination of growth promoting factors is described that allows growth of large amounts (10(10)-10(11)) of normal erythroid progenitors from chick bone marrow. These erythroid progenitors express the estrogen receptor (ER) as well as the receptor tyrosine kinase TGF alpha R/c-erbB. They require both TGF alpha and estradiol for sustained self-renewal in vitro, but terminally differentiate upon withdrawal of TGF alpha and inactivation of the ER by an antagonist (ICI 164.384). Overexpression of the human ER in erythroblasts devoid of endogenous ER revealed that the hormone-activated ER alone arrested erythroid differentiation and repressed a large group of erythrocyte genes. When similarly overexpressed, TGF alpha R/c-erbB inhibited the expression of a distinct, but overlapping, set of genes. The endogenous ER and TGF alpha R/c-erbB affect erythrocyte gene expression in a similar, but less pronounced fashion. Surprisingly, suppression of ER function by antagonist efficiently inhibited erythroblast transformation by tyrosine kinase oncogenes, suggesting a role of the endogenous ER in leukemogenesis. We speculate that the oncogenes v-erbB and v-erbA cooperate in erythroleukemia induction by a mechanism that is employed by TGF alpha R/c-erbB and ER to regulate normal progenitor self-renewal in response to external signals. PMID- 8458347 TI - Transduction of the light signal during complementary chromatic adaptation in the cyanobacterium Calothrix sp. PCC 7601: DNA-binding proteins and modulation by phosphorylation. AB - The cyanobacterium Calothrix sp. PCC 7601 can adapt its pigment content in response to changes in the incident light wavelength. It synthesizes, as major light-harvesting pigments, either phycocyanin 2 (PC2, encoded by the cpc2 operon) under red light or phycoerythrin (PE, encoded by the cpeBA operon) under green light conditions. The last step of the signal transduction pathway is characterized by a transcriptional control of the expression of these operons. Partially purified protein extracts were used in gel retardation assays and DNase I footprinting experiments to identify the factors that interact with the promoter region of the cpeBA operon. We found that two proteins, RcaA and RcaB, only detected in extracts of cells grown under green light, behave as positive transcriptional factors for the expression of the cpeBA operon. Treatment of the fractions containing RcaA and RcaB with alkaline phosphatase prevents the binding of RcaA but not of RcaB to the cpeBA promoter region. A post-translational modification of RcaA thus modulates its affinity for DNA. PMID- 8458348 TI - A simplified procedure for intra-arterial thrombolysis with tissue-type plasminogen activator in peripheral arterial occlusive disease: primary and long term results. AB - One-hundred and fifty patients with thrombotic and 60 patients with embolic occlusions of the superficial femoral and/or popliteal artery underwent a simplified IAT (intra-arterial thrombolysis) procedure. Ten mg rt-PA combined with 3000 IU Heparin were infused over 6 h, thereafter the extent of thrombolysis was checked fluoroscopically and the above mentioned treatment course repeated up to four times if necessary. The IAT regimen employed did not involve mechanical recanalization attempts; if complete thrombolysis revealed an underlying stenosis, a PTA (percutaneous transluminal angioplasty) was subsequently performed. IAT resulted in complete recanalization of 88 thrombotic occlusions (59%; 95% confidence interval: 50.8%-66.8%) and of 53 embolic occlusions (88%; 95% confidence interval: 77.1%-94.8% P < 0.001). In a further 33 (22%) thrombotic and four (7%) embolic occlusions IAT reduced the length of the occluded segment. At discharge, 102 (67%) patients with thrombotic and 55 (92%) patients with embolic occlusions were clinically improved. Overall, untoward effects occurred in 60 patients (29%): 47 (22%) were minor. Four patients (2%) suffered a systemic haemorrhage (three gastrointestinal, one macrohaematuria). The cumulative potency rate was significantly higher in patients with embolic occlusions throughout follow-up (82% vs 49% for thrombotic occlusions at 2 years, P < 0.001). Although all amputations were carried out in patients with thrombotic occlusions, follow up mortality did not differ significantly between patients with embolic and thrombotic occlusions. PMID- 8458349 TI - Prediction of mortality following hospital discharge after thrombolysis for acute myocardial infarction: is there a need for coronary angiography? European Cooperative Study Group. AB - The role of coronary angiography before hospital discharge after myocardial infarction was assessed in 1043 hospital survivors of the alteplase/placebo and the alteplase/PTCA trial of the European Cooperative Study Group. Forty-two of 1043 patients (4.0%) died after 1 to 489 days after predischarge coronary angiography. In survivors, follow-up ranged from 34 to 1106 days. In a stepwise multivariate regression model (Cox), use of diuretics and/or digitalis, a history of previous infarction and age exceeding 60 years were retained in the model with clinical data only. In addition, inability to perform exercise testing and less than 30 mmHg exercise-induced systolic blood pressure increase were selected by multivariate analysis. Large enzymatic infarct size, radionuclide left ventricular ejection fraction below 40%, and multivessel disease were also determinants of mortality after hospital discharge. The risk function, including coronary angiography, performed no better in late mortality prediction than functions based on clinical data and non-invasive testing. Patients without a history of previous infarction, not treated with diuretics and/or digitalis and with a systolic blood pressure increase of 30 mmHg or more during exercise had an excellent survival (98.6%) in the first year after hospital discharge, irrespective of whether symptoms of recurrent ischaemia occurred. This low risk group formed 47% of the total patient population and does not benefit from coronary angiography. PMID- 8458350 TI - 123I-metaiodobenzylguanidine scintigraphy in the detection of irregular regional sympathetic innervation in long QT syndrome. AB - Twelve patients with the long QT syndrome were studied to determine the usefulness of 123I-metaiodobenzylguanidine (MIBG) single-photon emission tomography (SPECT) at 2 h and 6 h after injection; the results were compared to 10 healthy volunteers (controls). Uptake of MIBG in the left ventricle at 2 h after injection was significantly reduced in patients with the long QT syndrome (1.43 +/- 0.13 vs 1.66 +/- 0.15 in controls, heart-to-mediastinum ratio, P < 0.002) and washout after 6 h was faster on a planar view image. Decreased MIBG uptake could be observed preferentially in the anterior and lateral walls near the apex. The half-time values of MIBG washout from the left ventricle were significantly reduced in the long QT syndrome (6.4 +/- 1.5 h) compared to controls (16.7 +/- 15.3 h, P < 0.002). In three cases, the same pattern of disturbed activity distribution was maintained even after surgical left cardiac sympathetic denervation. The present results strongly support the hypothesis that an inhomogenous regional distribution of sympathetic nerve terminals accompanied by an overall reduction in their absolute number may play an important role in the pathogenesis of the long QT syndrome. Additional functional disturbances, possibly related to the uptake of catecholamines in the left ventricle may coexist with regional inhomogeneity of nerve terminals. The differences observed from one case to the other may be related to the variation in severity of the disease. MIBG SPECT imaging seems an interesting new tool for the quantitative assessment of presynaptic sympathetic nerve terminal disturbances in the left ventricle of patients with the long QT syndrome. PMID- 8458351 TI - Left atrial spontaneous contrast echoes--markers of thromboembolic risk in patients with atrial fibrillation. AB - A consecutive series of 80 patients with atrial fibrillation were studied with both precordial and transoesophageal echocardiography. Left atrial spontaneous contrast echoes were observed in one patient with precordial echocardiography and in 26 patients (33%) with transoesophageal echocardiography. They were found most commonly in patients with rheumatic mitral valve disease (67%) but were observed in 28% of patients with lone atrial fibrillation. Their presence was unrelated to the age, gender and therapy of the patient. Although they were more common in patients with a large left atrium, they were sometimes observed in a normal sized atrial chamber. They were more common in chronic (40%) than in paroxysmal atrial fibrillation (5.6%). No patient had severe mitral regurgitation, but contrast echoes were observed in some patients with mild or moderate mitral regurgitation. Of the 26 patients with spontaneous contrast echoes, six (23%) had echoes consistent with left atrial thrombus compared to one of the 54 patients without these echoes (1.9%) (P = 0.006); 17 (65%) had suffered a previous thromboembolic event compared to 17 of the 54 without these echoes (32%) (P = 0.009). These data support the concept that spontaneous contrast echoes in the left atrium are associated with sluggish blood flow and a thrombogenic environment. Transoesophageal echocardiography may thus be useful in assessing which patients with atrial fibrillation might most benefit from anticoagulation. This hypothesis needs to be evaluated further in a prospective study. PMID- 8458352 TI - Vasodilator reserve in collateral-dependent myocardium as measured by positron emission tomography. AB - Myocardial blood flow can be accurately quantitated in patients using positron emission tomography and oxygen-15 labelled water. The purpose of this study was to determine the vasodilator reserve in myocardium completely perfused by intramyocardial collateral blood flow. We hypothesized that altered relative flow reserve in such regions would correlate with the degree of ischaemia observed in these patients during exercise. The technique involves the inhalation of the positron emitting tracer C15O2 which is converted to freely diffusible H2(15)O by the lung. With rapid dynamic scanning, arterial and regional myocardial tissue concentrations can be obtained and time activity curves generated. With a two compartment kinetic model, myocardial blood flow can be accurately quantitated over a wide range of blood flows. Five patients with stable exertional angina and normal ventricular function studies and who had an occluded major epicardial artery which completely opacified via intramyocardial collateral blood flow were studied. Myocardial blood flow (MBF) was measured both at rest and following an infusion of intravenous dipyridamole (0.56 mg.kg-1) and the results were compared with measurements obtained from a group of eight normal volunteers. During resting conditions, MBF in the control group was 0.86 +/- 0.10 ml.g-1.min-1 and in the patient group was 0.99 +/- 0.10 ml.g-1.min-1 in normally perfused myocardium (ns) and 0.86 +/- 0.14 ml.g-1.min-1 in collateral-dependent myocardium (ns). Following dipyridamole, MBF increased to 3.58 +/- 0.89 ml.g-1.min-1 in the control group and to 2.97 +/- 0.94 ml.g-1.min-1 in the normal regions of the patients (ns).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458353 TI - Relationship between myocardial collagen and echo amplitude in non-fibrotic hearts. AB - The aim of the study was to investigate the relationship between myocardial collagen and regional echo amplitude in humans with non-fibrotic myocardium. The ratio of myocardial collagen to total myocardial protein was determined as the hydroxyproline/leucine ratio in endomyocardial biopsies obtained from the right ventricular side of the interventricular septum in orthotopically transplanted hearts. Regional echo amplitude was measured in the interventricular septum. Patients were studied prospectively. Twenty-five patients (five female, 20 male) who had undergone orthotopic cardiac transplantation were studied 355 to 2939 days (1009 +/- 718, mean +/- SD) post-transplantation at the time of annual cardiac catheterization and endomyocardial biopsy. Patient ages varied from 22 to 62 years (46 +/- 11). Donor ages were 14 to 47 years (25 +/- 8) and the ischaemic time, 90 to 245 min (151 +/- 42). Cardiac transplantation was performed for end stage cardiac failure in all patients. The aetiology of cardiac failure was valvular heart disease in three, dilated cardiomyopathy in eight and ischaemic heart disease in the remainder. Echo amplitude studies were performed within 24 h of endomyocardial biopsy. All but one patient were on an immunosuppressive regime consisting of cyclosporine A and azathioprine with additional steroids in three. The remaining patient, who was the longest surviving patient in the study group, had never been treated with cyclosporine. This patient was maintained on steroids and azathioprine alone. No patient had clinical or histological evidence for acute cardiac rejection and all were clinically well. Five patients had angiographic evidence of coronary artery disease. All subject studies were performed at Harefield Hospital.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458354 TI - Left ventricular filling pattern in beta-thalassaemia major--a Doppler echocardiographic study. AB - The pattern of left ventricular filling was assessed by Doppler echocardiography in 38 adult beta-thalassaemia major patients; 28 with normal (age 25.2 +/- 5.3 years) and 10 with abnormal (age 24.5 +/- 8.8 years) left ventricular systolic function. The findings were compared with those obtained from 38 age and sex matched normal individuals. In patients with normal left ventricular systolic function, peak flow velocity in early diastole was higher than in the controls (94 +/- 16 vs 79 +/- 12 cm.s-1, P < 0.001). The peak flow velocity in late diastole was also greater (60 +/- 18 vs 46 +/- 9 cm.s-1, P < 0.001), but the ratio between the early and late (atrial) peaks was approximately the same in both groups (1.74 +/- 0.72 vs 1.70 +/- 0.30). There was no difference in deceleration time and rate between the two groups (152 +/- 32 vs 151 +/- 21 ms and 504 +/- 93 vs 508 +/- 115 cm.s-2 respectively). None of the patients had atrial predominant left ventricular inflow pattern. In patients with congestive heart failure the peak flow velocity in early diastole was greater than in the controls (96 +/- 10 vs 79 +/- 2 cm.s-1 P < 0.001) while in late diastole it was smaller (39 +/- 6 vs 44 +/- 2 cm.s-1, P < 0.05). The ratio between the early and late peaks was greater in the patients than in the controls (2.5 +/- 0.35 vs 1.8 +/- 0.08, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458355 TI - Left ventricular performance and ultrasonic myocardial quantitative reflectivity in endurance senior athletes: an echocardiographic study. AB - Young elite athletes often show left ventricular hypertrophy, but normal values of quantitatively evaluated myocardial wall reflectivity. The aim of this study is to assess the acoustic pattern of ventricular wall reflectivity, as well as of systolic and diastolic function, in older endurance runners with increased left ventricular mass. For this purpose, 12 elite, senior isotonic athletes in full training and 11 normal, age-matched controls with sedentary life styles were studied. The following parameters were measured with a commercially available 2D echo-Doppler machine: end-diastolic diameter, diastolic septum thickness, left ventricular mass index, ejection fraction (by Teicholtz rule); peak E, peak A, E/A ratio, acceleration and deceleration time of mitral inflow velocity and isovolumic relaxation time. On-line radio frequency analysis was also performed to obtain quantitative operator-independent measurements of the integrated backscatter signal of the ventricular septum and the posterior wall. The integrated values of the radiofrequency signals were normalized for the pericardial interface and expressed in percent (% 2D-IB). In spite of the greater left ventricular mass in athletes versus normal controls (319 +/- 81 vs 225 +/- 63 g.m-2, P < 0.0005), there were no significant intergroup differences as regards end-diastolic diameter (50.7 +/- 5.1 vs 48.1 +/- 5.2 mm, P = ns), ejection fraction (75.5 +/- 9.3 vs 71.8 +/- 9.1%, P = ns), and 2D-IB of septum (22.2 +/- 6.9 vs 22.4 +/- 7.0, P = ns) and posterior wall (12.5 +/- 5.6 vs 13.1 +/- 2.8, P = ns).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458356 TI - Early ventricular fibrillation in patients with acute myocardial infarction: correlation with coronary angiographic findings. AB - To define coronary angiographic characteristics of patients experiencing early primary ventricular fibrillation (VF) in the acute phase of myocardial infarction we studied 266 consecutive patients without clinical evidence of heart failure. Twenty-six patients (group 1) experienced early (< 12 h from the onset of symptoms of myocardial infarction) primary VF whereas 240 patients (group 2) with the same clinical characteristics served as an appropriately matched cohort. All patients were catheterized before or soon after hospital discharge (1 to 8 weeks after the acute event). There was no significant difference in left ventricular ejection fraction between the two groups of patients (39.6 +/- 6% vs 36.9 +/- 8%, P = ns). Patients with early VF had a significantly greater number of diseased vessels than those without VF (3.38 +/- 1.05 vs 2.03 +/- 1.25, P < 0.001) and a higher coronary arteriographic Gensini score (29.31 +/- 4.80 vs 20.16 +/- 4.14, P < 0.001). The left anterior descending coronary artery was identified as the infarct-related vessel in 53.6% of group 1 vs 44.5% of group 2 patients (P < 0.05). The mean maximal serum creatine kinase values were not significantly different (1897 +/- 1062 vs 1426 +/- 839 IU.l-1, P = ns) between the two groups. These data indicate that patients with early primary VF in the setting of acute myocardial infarction may have more extensive coronary artery disease than similar patients without VF. A worse prognosis could be anticipated for these patients on the basis of worse coronary anatomy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458357 TI - Left ventricular diastolic filling alterations in subjects with mitral valve prolapse: a Doppler echocardiographic study. AB - To assess left ventricular diastolic filling in mitral valve prolapse (MVP), we studied 22 patients with idiopathic MVP and 22 healthy controls matched for sex, age, body surface area and heart rate. A two-dimensional, M-mode and Doppler echocardiographic examination was performed to exclude any cardiac abnormalities. The two groups had similar diastolic and systolic left ventricular volumes, left ventricle mass and ejection fraction. Doppler measurements of mitral inflow were: E and A areas (the components of the total flow velocity-time integral in the early passive period of ventricular filling, E; and the late active period of atrial emptying, A), the peak E and A velocities (cm.s-1), acceleration and deceleration half-times (ms) of early diastolic rapid inflow, acceleration time of early diastolic flow (AT), total diastolic filling time (DFT) (ms), and the deceleration of early diastolic flow (cm.s-2). From these measurements were calculate: peak A/E ratio (A/E), E area/A area, the early filling fraction, the atrial filling fraction, AT/DFT ratio. All the Doppler measurements reported are the average of three cardiac cycles selected at end expiration. The mean peak A velocity, A/E velocity ratio, deceleration half time and atrial filling fraction were each significantly higher for subjects presenting a MVP (60 +/- 12 cm.s-1 vs 49 +/- 14, P < 0.008; 98 +/- 13% vs 64 +/- 12%, P < 0.0001; 120 +/- 36 ms vs 92 +/- 11, P < 0.002; 0.45 +/- 0.14 vs 0.36 +/- 0.08, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458358 TI - Usefulness of exercise testing performed with vasodilators for predicting the severity of myocardial ischaemia during daily activities and treatment. AB - Fifty patients (aged 53 +/- 7 years) with confirmed coronary disease performed two stress tests (baseline and following treatment with vasodilators) and were divided into two groups: (A) fixed ischaemic threshold (n = 27), and (B) variable ischaemic threshold (n = 23). All patients underwent 24-h baseline Holter monitoring and monitoring following treatment with nifedipine, placebo, propranolol and nifedipine + propranolol. In Group A, 92% of ischaemic episodes occurred at heart rates similar to those found during exercise testing. In Group B, the heart rate was lower in 66%. In Group A, positive stress testing before the first 3 min of exercise, or at < 140 beat,min-1 with ST segment depressions > or = 0.02 mV, correlated with higher Holter indexes. In Group A, propranolol reduced both the number of episodes and total ischaemia time. In Group B, the best effects were achieved with nifedipine and combined treatment. Our results further emphasize the contrasts between patients with angina and fixed and variable ischaemic thresholds and suggest that therapy tailored to the physiopathology may be most efficacious. PMID- 8458359 TI - Inter- and intra-observer variability in detection of patent foramen ovale with contrast echocardiography. AB - Patent foramen ovale is detected in-vivo using the technique of contrast echocardiography. A positive test depends on the ability of an observer to recognise micro-bubbles passing from the right to the left heart, and to differentiate them from background noise and/or chordae tendinae. To assess the inter- and intra-observer variability of this technique four observers reviewed independently, and on two separate occasions, 100 consecutive contrast studies stored on video tape. The proportions of agreement (95% CI) for each separate observer on the two occasions for the presence of patent foramen ovale were 0.91 (0.76-0.98), 0.88 (0.73-0.92), 0.80 (0.63-0.92) and 0.78 (0.60-0.91), and for its absence were 0.96 (0.88-0.99), 0.95 (0.87-0.99), 0.90 (0.81-0.96) and 0.91 (0.82 0.96), respectively. The proportions of agreement (95% CI) between all observers on the first viewing were 0.78 (0.72-0.84) for the presence and 0.91 (0.87-0.93) for the absence of patent foramen ovale. For the second viewing these were 0.81 (0.75-0.86) and 0.91 (0.88-0.94), respectively (P = NS, Chi-squared test). These results indicate that contrast echocardiography is subject to clinically acceptable inter- and intra-observer variability. PMID- 8458360 TI - Utilization of coronary angioplasty and cost of angioplasty disposables in 14 western European countries. European Angioplasty Survey Group. AB - An inventory has been made of the practice of angioplasty in 14 European countries from 1985 onwards. The numbers of procedures performed varied in 1985 from 3 to 186 per million inhabitants, in 1991 from 52 to 716. All countries showed a steady increase, but the highest performer. Belgium, achieved only 55% of the number of angioplasties performed in 1991 in the U.S.A. No relation was found between the number of angioplasties and death rate for ischaemic heart disease, national income, number of cardiologists or spending on health care. The number of catheterization laboratories was related to the number of procedures. Prices of angioplasty disposables varied widely between countries. In 1989 Italy and Spain had very high costs, averaging almost 2500 ECU and 2000 ECU for ACS and Schneider balloon catheters respectively, while Switzerland and the U.K. were cheap with costs between 700 ECU and 500 ECU for the same products. In 1991 average prices for balloon catheters fell by 25% in Spain, while in Switzerland average prices increased by 10%, bringing the almost four-fold price difference in 1989, down to a difference of 2.5 in 1991. If the U.S.A. is taken as a standard and set against the death rate from ischaemic heart disease in Western Europe in 1991 the number of 'missing' angioplasties was 215,500, the U.K. accounting for 42% of this deficit. PMID- 8458361 TI - Immediate and long-term results of percutaneous coronary angioplasty in patients aged 70 years or older. AB - Percutaneous coronary angioplasty (PTCA) nowadays appears as an attractive alternative to coronary artery by-pass grafting not only in young adults, but also in elderly patients. The aim of this study was to investigate the primary success, complications and long-term efficacy of PTCA in a consecutive series of 63 patients aged 70 years or over. Results are analysed in comparison to a younger group of 423 subjects who were submitted to PTCA during the same period of time. In the older group, PTCA was applied to 108 lesions. The angiographic success rate was 88%. Primary success was 87%, with a majority (91%) of complete revascularization. Failure of the procedure was recorded in eight patients (13%). Complications of PTCA were observed in three patients, (among these: one death). The outcome was excellent: out of 55 patients with successful angioplasty, 52 (94.6%) were asymptomatic at the time of hospital discharge. At follow-up (close to one year), 84.6% of the patients remained asymptomatic. The comparison with the younger group of patients showed no difference in terms of primary success, failure rate or incidence of complications. We therefore conclude that PTCA can be performed with safety and efficiency in patients aged 70 years or over. PMID- 8458362 TI - A multicentre, double-blind, placebo-controlled trial of quinapril in mild, chronic heart failure. AB - Angiotensin converting enzyme (ACE) inhibitors are of proven value in patients with severe chronic heart failure (CHF). Studies of the effects of ACE inhibitors on exercise capacity and quality of life in mild CHF have produced conflicting results. We have studied the effects of quinapril, a new ACE inhibitor with a relatively short plasma half-life, in mild CHF. Once daily (o.d.) dosing was compared with twice daily (b.i.d.) dosing in a three-way cross-over, double blind, placebo-controlled trial. Thirty-two patients (two female), mean age 59 (range 32-76) years were enrolled in three cardiology centres in the U.K. in 29 patients, and non-ischaemic in three. The mean (range) radionuclide ejection fraction was 20.4% (8%-47%). Following full familiarization with the protocol, the treadmill exercise time (modified Bruce protocol) was determined for each patient during a placebo run-in phase, and at the end of each of three 8-week double-blind treatment phases with quinapril o.d., quinapril b.i.d. (maximal total daily dose 20 mg) and placebo. Three patients were withdrawn due to adverse events while receiving quinapril (unstable angina, exacerbation of CHF and arrhythmia); there were no deaths and no patient was withdrawn due to hypotension. Mean exercise time (the primary end-point) was 65 s and 53 s longer in patients receiving quinapril o.d. and b.i.d. respectively compared to placebo (both P < 0.01, ANOVA). There was no significant period effect during the trial and no significant difference between the two quinapril dosing regimens. Quinapril had no significant effect on secondary end-points including ejection fraction, functional class and quality of life.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458363 TI - The acute response of left ventricular filling dynamics to intravenous verapamil predicts the changes in exercise tolerance after oral verapamil therapy in patients with hypertrophic cardiomyopathy. AB - We studied the correlation between changes in left ventricular filling dynamics induced by acute intravenous administration of verapamil and the changes in exercise tolerance induced by oral administration of the agent in 30 patients with hypertrophic cardiomyopathy. Diastolic cardiac function was measured by means of a nuclear stethoscope before and 10 min after intravenous administration of verapamil, 0.15 mg.kg-1 over 2 min. Treadmill exercise tests using a modified Bruce protocol were performed before the initiation of oral verapamil treatment and after 4 weeks of oral therapy at a dose of 320-360 mg.day-1 (mean +/- SD 332 +/- 17 mg.day-1). Peak filling rate (PFR) increased in 21 patients, 18 of whom (86%) also had an increase in exercise duration, PFR showed no increase in nine patients, eight of whom (89%) had no change in exercise duration (sensitivity 95%, specificity 73%, predictive value of the positive result 86%, predictive value of the negative result 89%). Acute changes in time from the beginning of rapid filling to PFR (t-PFR) and in left ventricular end-diastolic volume (EDV) were less useful in predicting improvement in exercise tolerance. In 19 patients the changes in PFR and EDV paralleled. Twelve of the 13 patients (92%) with an increase in both parameters also had an increase in exercise duration, whereas all six in whom these parameters were reduced showed no increase in exercise duration (sensitivity 100%, specificity 86%, predictive value of positive results 92%, and predictive value of negative results 100%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458364 TI - Acute effects of nifedipine, diltiazem and their combination in patients with chronic stable angina: a double-blind, randomized, cross-over, placebo-controlled study. AB - We evaluated the acute therapeutic effects of the oral administration of nifedipine (10 mg) and diltiazem (120 mg) alone and in combination in 16 patients with effort angina. The 16 patients (13 men and three women; mean age 59 +/- 7 years) performed a symptom-limited bicycle exercise stress test 3 h after placebo or active substance administration. Maximal work load, exercise duration and time to 1 mm ST segment depression were significantly increased and ST depression at peak exercise was significantly decreased by the combination of drugs. Nifedipine and diltiazem alone similarly improved exercise duration as markedly as their combination. One patient stopped the test after all three treatments for angina associated with ST depression > 2 mm. The combination of drugs yielded the best symptomatic effect: only four patients complained of angina in comparison to eight and seven patients after diltiazem and nifedipine, respectively. Nifedipine and diltiazem are effective and safe antianginal drugs. Some patients respond better to one drug than to the other. Patients who remain symptomatic in spite of maximal doses of a single drug may derive some benefit from combination therapy. PMID- 8458365 TI - Effects of flecainide on termination of atrial flutter by rapid atrial pacing. AB - Rapid atrial pacing is effective in terminating atrial flutter, but often results in transient or permanent atrial fibrillation rather than sinus rhythm. Class Ia antiarrhythmic drugs have earlier been shown to facilitate the direct conversion of atrial flutter to sinus rhythm. The present study was performed to test the hypothesis that flecainide, a group 1c antiarrhythmic drug, increases the direct conversion to sinus rhythm. In a series of 30 consecutive clinical episodes of atrial flutter treated with rapid atrial pacing, 12 episodes were in patients on flecainide treatment (group A), while in 13 episodes no patients were on group I antiarrhythmic drugs (group B). Direct conversion to sinus rhythm was achieved more often in group A (75%) than in group B (31%) P = 0.034. Both the flutter rates and the pacing rates used were lower in group A, 240 vs 280 beat.min-1 and 375 vs 430 b.min-1, respectively. Patients with atrial flutter in whom rapid atrial pacing is to be performed should be considered for pretreatment with flecainide. PMID- 8458366 TI - Diastolic intraventricular gradient in hypertrophic cardiomyopathy with apical hypertrophy. AB - Patients with hypertrophic cardiomyopathy and additional diastolic flow abnormalities are relatively rare. This report describes a case of apical ventricular hypertrophy with complete systolic obstruction and holodiastolic intraventricular pressure gradient. PMID- 8458367 TI - An unusual cause of myocardial infarction? AB - A young woman is described with acute inferior myocardial infarction due to a thrombus in the ascending aorta. The aetiology, the role of risk factors, the diagnostic value of transoesophageal echocardiography and angiography, and therapy, are discussed. PMID- 8458368 TI - A case of recurrent benign pericarditis treated by colchicine. AB - After five recurrences of idiopathic pericarditis over a period of 8 months on steroidal anti-inflammatory therapy, a splenectomized patient aged 31 years benefited from treatment with colchicine. He was treated for one year without any recurrence. A relapse occurred 6, 7 and 17 months after having stopped the drug. This observation raises the question whether colchicine might be beneficial in recurrent benign pericarditis with or without corticodependence and have a prophylactic action against recurrences. PMID- 8458369 TI - Expression and control of the natural autoreactive IgG repertoire in normal human serum. AB - We have investigated the autoreactive repertoire expressed by serum IgG of healthy individuals of various age groups using a large panel of self antigens. Natural IgG autoantibodies against all self antigens of the panel were found in the purified IgG fraction of the serum of all donors that were tested. The mean binding activity to self antigens of IgG of pregnant women was higher than that of IgG purified from the serum of infants, young adults and aged individuals. No increase in IgG autoreactivity was observed with aging neither in the purified IgG fraction of serum nor in whole serum. Whereas autoantibody activity was easily detectable in purified IgG, it was low in serum. No difference was observed, however, between the binding activity of purified IgG and of IgG in serum in the case of foreign antigens nor in the case of anti-thyroglobulin autoantibodies of patients with hashimoto's thyroiditis. Purified IgM from normal serum bound to F(ab')2 fragments of autologous IgG in a dose-dependent fashion and inhibited the binding of autologous IgG to self antigens. Our results thus indicate that autologous IgM contributes to regulate expression of the natural IgG autoreactive repertoire through V region-dependent interactions, resulting in low levels of IgG autoreactivity in serum under physiological conditions. PMID- 8458370 TI - T and B cell immune response to a 55-kDa endothelial cell-derived antigen in severe asthma. AB - Current concepts on the pathogenesis of chronic asthma emphasize the role of several inflammatory cell populations and their respective mediators that interact in a complex network. However, beside inflammatory cells, lymphocytes are also present in asthmatic airways. Although little is known about their involvement in asthma, it has been suggested that lymphocytes may participate in the development of chronic inflammation either through lymphokine secretion or through antibody production. In this study, we describe circulating IgG autoantibodies, directed against a common 55-kDa antigen shared by platelets and cultured endothelial cells, and found in 34 out of 97 asthmatic patients. Among epidemiological, clinical and biological characteristics of these asthmatic patients, the anti-55-kDa antigen antibodies are mainly restricted to patients with negative cutaneous prick tests (p = 0.0014), and corticosteroid-dependent asthma (p = 0.0036). These antibodies were also detected in a few patients with autoimmune disorders like systemic lupus erythematosus (3/30) or rheumatoid arthritis (2/36). Both platelet and endothelial cell antigens were cross reactive, had an isoelectric point between 8.0 and 9.0, were insensitive to reducing agents such as 2-mercaptoethanol, and were not present on either platelet or endothelial cell surface, as determined by immunostaining assay. [3H]Thymidine incorporation assay with peripheral blood mononuclear cells from patients in the presence or in the absence of 55-kDa antigen, purified from nitrocellulose sheets demonstrated a specific incorporation in 6 out of 13 patients with circulating anti-55-kDa antigen antibodies, with index values ranging from 12 to 3. Such a T cell reactivity has also been observed in 3 out to 17 patients without detectable serum anti-55-kDa antigen antibodies. Moreover, a significant correlation was found between index values of antigen-specific T cell reactivity and the forced expiratory volume in one second (r = 0.544, p = 0.003). Our data indicate that the detection of such antibodies allows to distinguish a subgroup of asthmatics in terms of severity and to suggest a relationship between clinical severity and T and B cell autoreactivity to the 55-kDa platelet/endothelial cell antigen. PMID- 8458371 TI - Effects of intrathymic injection of organ-specific autoantigens, parietal cells, at the neonatal stage on autoreactive effector and suppressor T cell precursors. AB - Thymectomy on day 3 after birth (3d-Tx) induces autoimmune gastritis (AIG) in 81%, and oophoritis (AIO) in 25% of BALB/c mice at the age of 2 to 3 months. Intrathymic, but not intraperitoneal injection of syngeneic parietal cells into sex-matched BALB/c mice within 24 h of birth resulted in almost complete prevention of the development of AIG in these mice in which 3d-Tx was performed. The prevention induced was parietal cell specific, since the development of AIO was not inhibited in female mice. Moreover, the injection of BALB/c liver cells, Mls-matched (BALB/c) and -disparate (DBA/2) B blasts which resulted in V beta 6 T cell deletion, as well as the injection of staphylococcal enterotoxin B failed to prevent the diseases. These findings suggested that recognition of an autoantigen in the thymus is necessary for the induction of tolerance, and that involvement of Mls-1 antigens in the pathogenesis of AIG, as has been suggested previously (Schwartz, R. H., Cell 1989. 57: 1073), was unlikely. T cells that suppress the development of organ-specific autoimmune diseases in 3d-Tx mice seem to maintain the unresponsiveness of autoreactive T cells at the periphery in normal mice. In agreement with our previous observations, we found that intraperitoneal (i.p.) injection of spleen cells from 3-month-old normal mice into 3d-Tx mice on day 10 after birth prevented the development of AIG, whereas spleen cells from age matched AIG+ (mice with AIG) or AIG- (mice without AIG) 3d-Tx mice failed to do this. This implies that the suppressor cells probably affect the differentiation of effector-precursor to effector. In fact, these suppressor cells did not inhibit the adoptive transfer of AIG to nu/nu BALB/c mice by spleen cells from 3d Tx mice manifesting AIG. By negative selection using monoclonal antibody and complement, it was confirmed that the phenotype of the suppressor cell was CD4. In contrast to 3d-Tx, 10d-Tx did not induce AIG, indicating the peripheralization of the suppressor cell by that time. On the other hand, intrathymic injection of parietal cells immediately after birth did not affect suppressor cell generation, implying that some T cells, including suppressor cells, escape thymus selection. We postulate that these cells correspond to the precursors of the autoreactive effector T cells and suppressor T cells that are present in normal mice. PMID- 8458372 TI - Clonal deletion of thymic mature T cells induced by staphylococcal enterotoxin B in murine fetal thymus organ culture. AB - The present study aims at investigating the intrathymic maturational stage of T cells at which clonal deletion can be induced. Staphylococcal enterotoxin B (SEB) was added to organ cultures of murine fetal thymus lobes at various time points of culture, and V beta 8-expressing cells were assayed on day 14. V beta 8 low expressing (V beta 8lo) cells were reduced to 40-60% of the control receiving no SEB, though the reduction was ambiguous when SEB was given on day 13. In marked contrast, V beta 8 high-expressing (V beta 8hi) cells were virtually completely deleted in all groups including the group given SEB on day 13. Most of the V beta 8hi cells that were deleted by 24 h of treatment with SEB were shown to be of the CD4+8- mature phenotype, though CD4-8+V beta 8hi cells were also deleted. It was further shown that the thymic V beta 8hi CD4+8- cells recovered from organs cultured for 14 days without SEB responded to immobilized anti-V beta 8 monoclonal antibody, indicating that V beta 8hi cells, which were highly sensitive to clonal deletion, were functionally competent mature T cells. These results strongly suggest that the thymus is capable of eliminating all T cells recognizing antigen present in the thymus regardless of the maturational stage of T cells. PMID- 8458373 TI - Increased and highly stable levels of functional soluble interleukin-6 receptor in sera of patients with monoclonal gammopathy. AB - Soluble human interleukin-6 receptor (sIL-6R) was measured in the serum of 30 healthy individuals, 32 individuals with monoclonal gammopathy of undetermined significance (MGUS), 20 patients with early multiple myeloma (MM) and 54 patients with overt MM. The serum activity recognized by an immunoradiometric assay was determined to be sIL-6R, because of its binding capacity to IL-6 and its molecular mass of 55 kDa. All sera of healthy individuals contained sIL-6R (mean value: 89 ng/ml, range 17-300 ng/ml). Serum sIL-6R levels were increased by 51% in patients with MGUS (mean value: 135 ng/ml, p < 0.005), by 44% in patients with early myeloma (mean value: 128 ng/ml, p < 0.001) and by 116% in patients with overt MM (mean value: 193 ng/ml, p < 0.001). In patients with MM, a complete lack of correlation (p > 0.7) was found between serum sIL-6R levels and other previously recognized prognostic factors in this disease, particularly serum IL-6 levels and those factors related to tumor cell mass. The independence of serum sIL-6R levels on tumor cell mass was directly demonstrated by studying four patients with MM treated with autologous bone marrow transplantation for periods of between 320 and 760 days. These levels were found to be remarkably stable and constant, independent of whether patients relapsed or achieved complete remission. Finally, physiological concentrations of sIL-6R were found to increase by tenfold the sensitivity of human myeloma cell lines to IL-6. These observations suggest a high control of the sIL-6R level in vivo, and, possibly, an important functional role of this circulating protein in patients with monoclonal gammopathies. PMID- 8458374 TI - The human immunoglobulin VH7 gene family consists of a small, polymorphic group of six to eight gene segments dispersed throughout the VH locus. AB - In this report we describe the analysis and mapping of members of the human immunoglobulin VH7 gene family. VH7 and VH1 gene segments are closely related, with individual gene segments sharing between 78% and 82% sequence identity. Divergence from VH1 gene sequence occurs as an abrupt event at the boundary between framework region (FR) 2 and complementarity-determining region (CDR) 2 and continues through a major portion of FR 3. We used polymerase chain reaction amplification to create a 162-base pair probe spanning the family-specific region of CDR 2 and FR 3 that proved suitable for standard Southern analysis of genomic DNA. The VH7 gene family was found to be a small but discrete VH gene family consisting of five to eight germ-line elements, of which at least three are polymorphic. Four different VH7 gene segments were cloned from the germ line of a single individual, and assigned to specific restriction fragments by sequence specific hybridization. Two of the four VH7 elements were pseudogenes. The pattern of sequence variation in these and other known pseudogenes suggests that these nonfunctional elements may play a role in the evolution of novel VH families. A combination of one and two-dimensional pulsed field gel electrophoresis was employed to map the chromosomal location of all of these VH7 elements. Individual VH7 gene segments were found to be dispersed over a region of at least 940 kb of DNA, and interspersed with members from other VH gene families. The polymorphism of the VH7 gene segments and their scattered location throughout the VH locus makes them potentially useful markers for mapping and linkage studies. PMID- 8458375 TI - The major histocompatibility complex-encoded proteasome component LMP7: alternative first exons and post-translational processing. AB - The LMP7 gene maps to the major histocompatibility complex class II region. The derived protein sequence shares homology with N-terminal amino acid sequence from proteasome subunits (Glynne, R., Powis, S. H., Beck, S., Kelly, A., Kerr, L.-A. and Trowsdale, J., Nature 1991. 353: 357) and it has been suggested that LMP7 is involved in the degradation of endogenous antigens prior to their presentation through class I (Robertson, M., Nature 1991. 353: 300). We have isolated a second LMP7 transcript which has a different first exon to the published sequence. Both transcripts were expressed in cell lines from a number of tissues and both responded to interferon-gamma. An anti-LMP7 antiserum precipitated proteins similar in their migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis to those precipitated by an anti-proteasome serum. Western blot analysis of anti-proteasome precipitates demonstrated that the LMP7 protein is incorporated into the proteasome but has a molecular mass of 23 kDa, 7 kDa smaller than expected fro the derived protein sequence of either of the cDNA. A pulse-chase experiment indicated that post-translational cleavage of the LMP7 N terminus precedes the formation of the 23-kDa proteasome subunit. To our knowledge, LMP7 provides the first biochemical evidence for such processing of proteasome components. PMID- 8458376 TI - In vivo induction of the nitric oxide pathway in hepatocytes after injection with irradiated malaria sporozoites, malaria blood parasites or adjuvants. AB - The mechanisms responsible for malarial immunity induced by repetitive injections of X-irradiated sporozoites have not been fully established. We demonstrate here that a single injection of irradiated sporozoites induced, as soon as 24 h after, a non-permissive state to hepatocyte reinfection with sporozoites in vitro. The same effect was observed when malarial blood forms, irradiated promastigotes of Leishmania infantum, adjuvants (muramyl dipeptide, poly acidylic uridylic) or interferon-gamma was injected. Activation of the nitric oxide (NO) pathway in the hepatocyte by these factors was found to be responsible for hepatocyte refractory status. Additionally, this metabolic pathway is involved in protection given by repeated injections of irradiated sporozoites since protection could be reversed by treating mice at the time of sporozoite challenge with a competitive inhibitor (NG-monomethyl-L-arginine) of the NO pathway. These results suggest that, in view of an antisporozoite vaccine, further studies are needed to find out how to activate specifically a long-lasting nonspecific immune response. PMID- 8458377 TI - Mutation of Asp20 of human interleukin-2 reveals a dual role of the p55 alpha chain of the interleukin-2 receptor. AB - Mutation of Asp20 in human interleukin-2 (IL-2) to Lys is known to result in an IL-2 molecule with unchanged binding to the p55 subunit of the IL-2 receptor, but with greatly decreased affinity for the p75 subunit (Collins, L., Tsien, W.-H., Seals, C. et al. Proc. Natl. Acad. Sci USA 1988. 85: 7709). Here we demonstrate that Lys20 IL-2 competed with a reduced (10-fold) affinity for high-affinity IL-2 receptors on two murine cell lines HT2 and CTLL. In parallel with this difference in receptor interaction, Lys20 IL-2 stimulated half-maximal HT2 cell proliferation at a 10-fold higher concentration than wild-type IL-2. However, half-maximal stimulation of CTLL cells required a 100-fold higher concentration of Lys20 IL-2. A similar 100-fold reduction in bioactivity of Lys20 IL-2 was observed for primary, activated, human or murine lymphocytes. Anti-p55 antibodies increased the concentration of Lys20 IL-2 required to stimulate HT2 cells to that required for CTLL cells. These data suggest that CTLL cells, while able to bind Lys20 IL-2 with high affinity, are lacking a p55-dependent function necessary for optimal stimulation. Therefore, p55 has a dual role, being important both for high-affinity IL-2 binding and for optimal cell triggering. PMID- 8458378 TI - Analysis of cytokine gene expression in subpopulations of freshly isolated thymocytes and thymic stromal cells using semiquantitative polymerase chain reaction. AB - Using a semi-quantitative polymerase chain reaction (PCR) technique we have examined the expression of a panel of cytokines during thymus development, localizing the expression to individual components of the thymic stroma and thymocytes at different maturational stages. The expression of interleukin (IL) 7, stem cell factor (SCF), IL-1 alpha and granulocyte-monocyte-colony-stimulating factor (GM-CSF) mRNA was mapped to individual stromal cell types, while the expression of IL-1 alpha and GM-CSF, along with interferon (IFN)-gamma and IL-4 was detected in the lymphoid compartment of fetal day (Fd) 14 thymus. The expression of lymphoid-specific cytokines genes was selectively down-regulated in thymocytes undergoing maturation. CD3-/lo4+8+ cells, representing an intermediate stage of thymocyte maturation, were devoid of cytokine gene expression. Their CD3+ progeny, on the other hand, expressed IFN-gamma mRNA, supporting the notion that positive selection of cells for further maturation induces the reexpression of some cytokine genes. The cytokine profiles of the various stromal components differed. Purified major histocompatibility complex class II+ cortical epithelial cells strongly expressed IL-7 and SCF, but only limited expression of IL-1 alpha and GM-CSF could be detected. Fetal mesenchyme, on the other hand, expressed SCF, IL-1 alpha and GM-CSF but not IL-7. The importance of these cytokine profiles in relation to T cell development is discussed. PMID- 8458379 TI - Direct evidence for anergy in T lymphocytes tolerized by oral administration of ovalbumin. AB - The present study investigated bystander suppression, specific suppression and anergy as mechanisms for oral tolerance. Oral tolerance was induced in mice by a single gastric intubation of 20 mg ovalbumin (OVA) and was evaluated in vitro by the absence of T lymphocyte proliferative responses to OVA after priming by OVA complete Freund's adjuvant (CFA). T lymphocyte unresponsiveness was antigen specific, systemic and was not affected by the vehicle used for immunization. T lymphocytes derived from tolerant popliteal lymph nodes (PLN) responded to an acetone precipitate (AP) of mycobacteria present in CFA; this response was not suppressed by co-culture with OVA, thereby arguing against a mechanism of bystander suppression in our system. Responses of PLN T lymphocytes derived from OVA-CFA primed, non-tolerant mice, or those of an OVA-specific T lymphocyte line, were not suppressed by PLN or spleen cells derived from OVA tolerant mice. These results excluded the possibility that oral tolerance was induced and maintained by a mechanism of specific suppression. At the cellular level, we found that OVA tolerant T lymphocytes did not produce interleukin-2 (IL-2) nor express IL-2 receptor in response to OVA stimulation in vitro; both observations are indicative of a state of anergy. Incubation of OVA-tolerant PLN T lymphocytes together with murine recombinant IL-2 for 5 days, released anergic T lymphocytes and a concomitant OVA-specific proliferative response of CD4+ T cells was detected. Taken together, our experimental system excludes the involvement of bystander or specific suppression in the induction of oral tolerance to OVA, and provides direct evidence to show that oral tolerance results from specific T lymphocyte anergy. PMID- 8458380 TI - The transcription factor Pit-1/GHF-1 is expressed in hemopoietic and lymphoid tissues. AB - The expression of the Pit-1/GHF-1 transcription factor (hereafter Pit-1), which controls the expression of growth hormone (GH) and prolactin (PRL) in the pituitary gland, has been documented in human and rat hemopoietic and lymphoid tissues and cell lines. Pit-1 mRNA was detected by in situ hybridization in about 1% of rat bone marrow cells and in the spleen red pulp and marginal zone. Pit-1 was also expressed in human tonsils (mantle zone), in the thymus (rat and human, non-lymphoid cells), in lipopolysaccharide-stimulated rat peritoneal cells and in non-hepatocyte cells in the liver (rat and human). A detailed investigation of the rat spleen showed a very similar distribution for Pit-1, GH and PRL mRNA and Pit-1, GH and PRL proteins (detected by immunocytochemistry). Using polymerase chain reaction followed by Southern hybridization, the expression of Pit-1 could be confirmed in human and rat spleen, bone marrow and thymus. HL60 and RAJI leukemic cells were also positive. The sequence of fragments amplified from rat spleen and from human bone marrow completely matched published sequences of rat and human pituitary Pit-1, respectively. Expression of GH and PRL in lymphoid tissues has been documented. The straightforward hypothesis would therefore be that Pit-1's main function in lymphoid tissues is controlling GH and PRL expression, as in the pituitary gland. GH and PRL may be hemopoietic and lymphoid growth and differentiation factors. PMID- 8458381 TI - Human peripheral blood eosinophils produce and release interleukin-8 on stimulation with calcium ionophore. AB - We present evidence that human blood eosinophils produce interleukin (IL)-8 when stimulated with calcium ionophore. Following in vitro culture of 99% pure eosinophils with calcium ionophore, released IL-8 was detectable by enzyme-linked immunosorbent assay in supernatants. Eosinophil IL-8 production was considerably greater than that of IL-3 or granulocyte macrophage colony-stimulating factor. Furthermore, eosinophil production of IL-8 in the presence of calcium ionophore could be inhibited with the immunomodulating agent cyclosporin A and the protein synthesis inhibitor cycloheximide. In addition, following stimulation of highly purified blood eosinophils with calcium ionophore, IL-8 mRNA was detectable after polymerase chain reaction amplification. In comparison with other cells on stimulation with calcium ionophore, eosinophils produce about half as much IL-8 as neutrophils but significantly more than purified T cells. In contrast to monocytes and neutrophils, IL-8 production was not inducible with IL-1 or tumor necrosis factor. Finally, following calcium ionophore stimulation blood eosinophils were shown to contain cytoplasmic IL-8 by employing a monoclonal antibody against IL-8 in conjunction with immunohistochemistry. These observations demonstrate that eosinophils are capable of IL-8 production and release, which may contribute to defense against parasites and to the pathophysiology of allergic and asthmatic disease. PMID- 8458382 TI - A subset of anti-CD21 antibodies promote the rescue of germinal center B cells from apoptosis. AB - Germinal center cells (GCC) are programmed to die by apoptosis unless they receive a positive signal for rescue. The primary signal in vivo is believed to be dependent on interaction with antigen held as immune complexes on follicular dendritic cells (FDC), a subset of which express large amounts of CD23, a low affinity receptor for IgE. Recombinant soluble CD23 (sCD23) and interleukin-1 have been found to potentiate the survival of GCC in vitro. Recently, CD23 was shown to interact specifically with a ligand other than IgE, namely CD21 (CR2/Epstein-Barr virus receptor). In the present study, we show that a subset of anti-CD21 monoclonal antibodies behave similarly to soluble CD23 in their effect on GCC inasmuch as they: (i) diminish the occurrence of apoptosis; (ii) promote a plasmacytoid appearance in rescued cells; (iii) up-regulate expression of the Bcl 2 proto-oncogene. These findings indicate that FDC-derived CD23 exerts its effects on GCC via CD21. PMID- 8458383 TI - Pathogenic autoimmunity to affinity-purified mouse acetylcholine receptor induced without adjuvant in BALB/c mice. AB - Myasthenia gravis (MG) and experimental autoimmune myasthenia gravis (EAMG) are antibody-mediated disorders in which anti-acetylcholine receptor (anti-AChR) antibodies cause loss of muscle AChR and subsequent weakness. Many species are susceptible to induction of EAMG with purified xenogeneic AChR in adjuvant, but injection of Torpedo AChR without adjuvants can also induce evidence of EAMG. To see whether pathogenic autoimmunity could be induced in mice by isolated mouse AChR we injected BALB/c mice with several doses (1 pmole; about 0.1 microgram) of affinity-purified AChR (from the BC3H1 cell line but thought to be identical with denervated mouse muscle) intraperitoneally, without adjuvant, over a period of 10 22 weeks. Some of the mice became ill and died. High levels of serum anti-mouse AChR, directed mainly towards the main immunogenic region, were found and, in the survivors, correlated with loss of muscle AChR. Thus BALB/c mice can mount an autoimmune response to minute amounts of mouse AChR, without the use of adjuvants, and this response is very similar to that found in MG. This novel finding has implications regarding the etiology of the human disease. PMID- 8458384 TI - Reactive oxygen product formation after Fc gamma receptor-mediated neutrophil activation by monomeric mouse IgG2a: implications for the generation of first dose effects after OKT3 treatment. AB - In the present study, we provide evidence that IgG2a monoclonal antibody (mAb) OKT3 is able to induce reactive oxygen intermediate (ROI) formation in polymorphonuclear leukocytes (PMN) when Fc gamma RIIIB as well as Fc gamma RII are bound concomitantly. Inhibition of binding to either Fc gamma R by specific mAb (3G8 or IV.3, respectively) resulted in complete abrogation of the OKT3 induced respiratory burst. The effect of OKT3 was independent from its specificity and thus also from its T cell-activating property, since nonbinding IgG2a isotype controls induced similar amounts of ROI. The IgG2b mAb BMA031 as well as the respective nonbinding isotype control were only minimally effective. With regard to the potential role of PMN activation in inflammation and tissue damage, our findings offer an extended explanation for the generation of initial adverse reactions to OKT3. Thus, one might speculate that the concerted action of cytokines liberated after its administration, what may lead to margination of leukocytes, and activation of PMN via Fc gamma R might produce first-dose reactions to OKT3 by directing radical-mediated damage against the endothelium. PMID- 8458385 TI - Rat intestinal epithelial cell line IEC-6 is activated by recombinant interferon gamma to inhibit replication of the coccidian Toxoplasma gondii. AB - Toxoplasma gondii tachyzoites invaded and replicated in cultured rat small intestine cells of the line IEC-6. Treatment of rat small intestine cells with murine recombinant interferon-gamma resulted in a dose-dependent inhibition of intracellular T. gondii replication. This could be of relevance as a first line defense against Toxoplasma infection. PMID- 8458386 TI - Interleukin 6 is not required for antigen-specific antibody responses by human B cells. AB - Interleukin-6 (IL-6) is a late-acting differentiation factor for human B cells activated by polyclonal mitogens such as pokeweed mitogen (PWM) and Staphylococcus aureus Cowan strain I, but its role in specific antibody responses has not been established. We show here that IL-6 has no consistent effect on specific antibody responses by tonsillar mononuclear cells (TMC) stimulated with influenza virus. A blocking IL-6 antibody also had no effect on antibody production, suggesting that endogenous IL-6 production was not required. In control experiments, this antibody inhibited PWM-stimulated immunoglobulin secretion and proliferation of the IL-6-dependent B cell line B9. A requirement for IL-6 in responses of unfractionated TMC may have been disguised by the presence of T cells. To overcome this problem, we investigated the effect of IL-6 on specific antibody production by T-depleted B cells stimulated with antigen in the presence of IL-2, which is a T cell replacing factor (TRF) for human B cells. Specific antibody production was restored by IL-2, but not IL-6. Neither IL-6 nor anti-IL-6 antibody had any consistent effect on specific antibody production by purified B cells stimulated with antigen and TRF. These experiments show that IL 6 does not have a significant role in antigen (influenza virus)-specific antibody responses by human B lymphocytes. PMID- 8458387 TI - Human interleukin-4 receptor signaling requires sequences contained within two cytoplasmic regions. AB - The signaling pathway used by the murine or human interleukin-4 receptor (hIL-4R) has not been elucidated so far. As an approach to mapping the cytoplasmic regions of the hIL-4R that are essential for mediating the biological response upon IL-4 binding we have cloned and expressed the wild-type hIL-4R and several cytoplasmic deletion mutants in the murine IL-3-dependent pro-B cell line BA/F3. Transfection of the wild-type hIL-4R conferred the ability on BA/F3 cells to proliferate in a dose-dependent way when treated with human IL-4. The analysis of six deletion mutants indicated that the signaling function of the hIL-4R depends on sequences within two discontinuous regions that are located between amino acid IIe233 and Ser365 and Thr462 and Ala580 of the intracytoplasmic domain. The deletion of either of these regions totally abrogated IL-4-inducible growth. The relevance of our data is discussed in relation to the results obtained from similar studies with other members of the hematopoietin receptor superfamily. PMID- 8458388 TI - Eosinophils infiltrating interleukin-5 gene-transfected tumors do not suppress tumor growth. AB - Tumor-associated eosinophils have been observed in human tumors and in experimental tumor models, but their function is poorly understood. To study the role of eosinophils during tumor growth, the plasmacytoma J558L and the mammary adenocarcinoma TS/A were transfected with an expression vector encoding the murine gene for interleukin-5 (IL-5), a cytokine inducing proliferation and activation of eosinophils. Injection of parental cells, mock-transfectants and IL 5-producing cells into syngeneic mice showed that local IL-5 secretion induced rapid tumor infiltration by eosinophils, as evidenced by immunohistochemical staining, but nevertheless did not alter the tumor growth kinetics of IL-5 transfectants. Therefore, the mere presence of IL-5 and eosinophils was not sufficient to induce a protective host immune response. PMID- 8458389 TI - Chronic treatment with haloperidol modifies the sensitivity of autoreceptors that modulate dopamine release in rat striatum. AB - The effects of apomorphine or sulpiride on electrically evoked dopamine release from striatal slices of rats pretreated with haloperidol were investigated. Chronic haloperidol treatment (1 mg/kg per day for 21 days) significantly reduced electrically evoked dopamine release from striatal slices until 72 h after the last injection. The apomorphine-induced reduction and the sulpiride-induced increase in evoked dopamine release were significantly enhanced by the chronic treatment with haloperidol at 72 h after the last injection. The enhancement of the sulpiride-induced increase in evoked dopamine release was inversely correlated with the dopamine release evoked by the first stimulation in striatal slices from haloperidol-treated (r = -0.85, n = 12, P < 0.01) but not from saline treated rats. These results suggest that an increase in the sensitivity of dopamine autoreceptors due to chronic treatment with haloperidol could partially account for the reduction in dopamine release from striatal slices of rats. PMID- 8458390 TI - Effects of (S)-nafenodone on 45Ca2+ fluxes and contractions in rat isolated vascular smooth muscle. AB - The effects of (S)-nafenodone, a new antidepressant, were studied on contraction and 45Ca2+ fluxes in rat vascular smooth muscle. In isolated rat aorta (S) nafenodone, 10(-7) - 10(-4) M, inhibited the contractions induced by 80 mM KCl (IC50 = 1.4 +/- 0.4 x 10(-5) M) and 10(-5) M noradrenaline (IC50 = 1.2 +/- 0.2 x 10(-5) M). (S)-Nafenodone relaxed the contractions induced by both high K+ and noradrenaline, this effect being independent of the presence of functional endothelium. It also inhibited the contractions induced by addition of CaCl2 to Ca(2+)-free high-K+ solution IC50 = 2.5 +/- 0.9 x 10(-6) M) and the phasic contractions induced by noradrenaline in Ca(2+)-free medium, but was a very weak relaxant of the contractions induced by phorbol 12-myristate-13-acetate in Ca2+ free medium. In addition, (S)-nafenodone inhibited the spontaneous mechanical activity in portal vein segments (IC50 = 1.4 +/- 0.8 x 10(-6) M). (S)-Nafenodone inhibited the 45Ca2+ uptake stimulated by high KCl or noradrenaline without altering 45Ca2+ uptake in resting strips and decreased the net 45Ca2+ content in aortic strips non-stimulated as well as stimulated by noradrenaline. In conclusions, (S)-nafenodone inhibited voltage- and agonist-stimulated Ca2+ entry in isolated rat aortas. In addition, it decreased Ca2+ content in both resting and noradrenaline-stimulated muscles, suggesting that it may deplete noradrenaline-sensitive intracellular Ca2+ stores. As a consequence, (S) nafenodone would reduce the concentration of intracellular free Ca2+ available at the contractile apparatus for vascular smooth muscle contraction. PMID- 8458391 TI - In vitro extracellular recording from nigral dopamine neurons following continuous d-amphetamine infusion. AB - Single nigral dopamine neurons were extracellularly recorded in vitro after withdrawal from continuous d-amphetamine sulfate infusion (5.0 mg/kg per day for 7 days via subcutaneous osmotic minipumps). Seven days after withdrawal, the dopamine neurons were supersensitive to impulse-inhibition by dopamine. This increased sensitivity suggests a supersensitivity of soma/dendritic autoreceptors on these neurons, as we previously hypothesized based on a supersensitivity to intravenous apomorphine. In contrast to the day 7, the withdrawal day 1 was associated with a normosensitivity to dopamine, suggesting that the apomorphine subsensitivity observed in vivo on this day may be secondary to non-autoreceptor changes. PMID- 8458392 TI - Chronic sabeluzole treatment of cultured rat cerebellar granule cells reduces N methyl-D-aspartate-induced inward current. AB - The effects of sabeluzole, a drug that protects rat hippocampal neurones from glutamate- and N-methyl-D-aspartate (NMDA)-induced toxicity, were investigated in rat cerebellar granule cells in vitro with the whole-cell voltage clamp technique. Acute exposure of 0.1 microM sabeluzole for 20 min prior to experiments did not significantly affect glutamate receptor-mediated inward currents. Conversely, exposure of cultured granule cells to sabeluzole for 7 days reduced the NMDA-induced inward current and did not affect the non-NMDA responses evoked by kainic acid. The results suggest that chronic treatment with sabeluzole selectively reduces the functional NMDA response. PMID- 8458393 TI - Effects of eseroline on the ventilatory response to CO2. AB - The effect of eseroline on the normoxic hypercapnic ventilatory response was assessed in nine alpha-chloralose-urethane-anaesthetized cats. The ventilatory responses to step changes in end-tidal PCO2 were determined before (control), during i.v. infusion of eseroline (bolus of 1.2 mg.kg-1 followed by 0.65 mg.kg-1 x h-1) and 1 h after the end of the infusion. Each response was separated into central and peripheral chemoreflexes, characterized by CO2 sensitivity, time constant, time delay and apnoeic threshold. We found that eseroline depressed ventilation by affecting both tidal volume and breathing frequency. The ventilatory response to CO2 was depressed due to a decrease in the CO2 sensitivity of peripheral chemoreceptors from 0.20 to 0.12 l.min-1 x kPa-1 and in the CO2 sensitivity of central chemoreceptors from 1.04 to 0.50 l.min-1 x kPa-1 (P < 0.01). However, the ratio of these sensitivities was not changed, like the apnoeic threshold. The depressant effect was reversed by naloxone. We conclude that the depressant effect of eseroline on ventilatory response to CO2 is mainly due to an action on the respiratory integrating centres in the brainstem rather than on the CO2 sensitivity of peripheral and central chemoreceptors. PMID- 8458394 TI - Endothelium-dependent vasodilator responses of the isolated mesenteric bed are preserved in long-term streptozotocin diabetic rats. AB - Endothelium-dependent and endothelium-independent responses to exogenous vasoactive substances were compared in isolated, perfused mesenteric beds from control rats and in rats subjected to prolonged (15-17 weeks) streptozotocin induced diabetes. The main aim of the study was to determine whether the prolonged period of diabetes altered vascular endothelial function, and thereby modified vascular responsiveness to vasoconstrictors or vasodilators. Noradrenaline induced vasoconstriction was not significantly altered in preparations from diabetic rats compared to control. Vasodilator responses to acetylcholine (ACh) and ATP were endothelium-dependent, since they were greatly reduced or abolished after endothelium removal by perfusion with 0.1% Triton-X 100. The vasodilator action of these agents was fully preserved in the diabetic animals. Sodium nitroprusside produced a vasodilation which was endothelium independent, this vasodilation was also preserved in the diabetic animal. We conclude that prolonged streptozotocin-induced diabetes does not reduce the ability of the mesenteric vascular endothelium to release vasodilator substances, nor does it alter the responsiveness of the bed to exogenous endothelium independent vasodilator sodium nitroprusside or vasoconstrictor noradrenaline. PMID- 8458395 TI - Muscarinic M1 receptor agonist actions of muscarinic receptor agonists in rabbit vas deferens. AB - In the electrically field-stimulated rabbit vas deferens, muscarinic receptor agonists increase twitch-height by actions at postjunctional M2 receptors and decrease twitch-height by actions at prejunctional M1 receptors. In the present studies, in contrast to previous reports, muscarinic receptor agonists primarily decreased twitch-height, produced minimal increases in twitch-height, and, produced identical responses in both epididymal and prostatic tissue segments, thus permitting a more detailed investigation of the M1 receptor component of action of muscarinic receptor agonists in the rabbit vas deferens. The nonselective muscarinic receptor agonist carbachol produced biphasic effects on twitch-height in the vas deferens: lower concentrations increased twitch-height to only approximately 25-30% over control, whereas higher concentrations inhibited the twitch. The selective M1 receptor antagonist pirenzepine blocked the inhibitory effects of carbachol, and unmasked carbachol-induced increases in twitch-height. Atropine, 4-DAMP (4-diphenylacetoxy-N-methylpiperidine methiodide) and AF-DX 116 (11-2[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro- 6H-pyrido[2,3-b][1,4]benzodiazepin-6-one) blocked both the inhibitory and stimulatory effects of carbachol, but atropine and 4-DAMP were more potent in blocking the inhibitory than the stimulatory effects of carbachol, whereas the reverse was true for AF-DX 116. McN-A-343 (4-hydroxy-2-butynyl)trimethylammonium chloride, m-chlorocarbanilate) and 12 other muscarinic receptor agonists from a variety of chemical classes also produced concentration-dependent decreases in twitch-height. The log IC50s of the muscarinic receptor agonists for decreasing twitch-height were highly correlated with their log Kis for inhibiting [3H]pirenzepine (r = 0.96) and [3H]oxotremorine-M (r = 0.85) binding in rat hippocampal membranes. The present results demonstrate that the muscarinic M1 receptor mediating inhibition of twitch-height in the rabbit vas deferens has pharmacologic properties similar to the muscarinic M1 receptor in rat hippocampus. PMID- 8458396 TI - CCKA receptors mediate slow depolarizations in cultured mammalian sympathetic neurons. AB - The effect of cholecystokinin octapeptide (CCK-8) was examined in guinea-pig celiac ganglion (CG) neurons in primary culture using standard intracellular recording techniques. Sulfated CCK-8 (CCK-8S; 1 microM) evoked slow depolarizing responses in 94% of CG neurons tested. In contrast, membrane potential was not affected by nonsulfated CCK-8 (CCK-8NS; 1 microM), CCK tetrapeptide (CCK-4; 1 microM), or gastrin (1 microM). The selective CCKA receptor antagonist L 364,718 potently inhibited CCK-8S-induced slow depolarizations (IC50 2.9 pM). In contrast, the selective CCKB receptor antagonist L 365,260 was a weak inhibitor of CCK-8S-induced slow depolarizations (IC50 1.3 microM). The depolarizing responses to CCK-8S were associated with an average increase in cell input resistance of 61%. Single electrode voltage clamp experiments indicated that CCK 8S-induced depolarizations were associated with a slow inward shift in holding current. Thus, the present findings indicate that guinea-pig cultured CG neurons are endowed with excitatory CCKA receptors the activation of which elicits a decrease in membrane conductance, thereby resulting in slow depolarizations. PMID- 8458397 TI - The effect of neonatal capsaicin on the development of bronchial hyperresponsiveness in allergic rabbits. AB - We have investigated the effects of neonatal capsaicin treatment of rabbits on the development of bronchial hyperresponsiveness following allergen exposure from birth. In vivo airways responsiveness was assessed as the concentrations of histamine to cause a 35% decrease in compliance (PC35) and a 50% increase in resistance (PC50). Rabbits treated with vehicle capsaicin (10% ethanol, 10% tween 80 and 80% saline) and then immunised with Altenaria tenius (40,000 protein nitrogen units (PNU)/ml + AL(OH)3 + saline in a ratio 2:1:1) were more responsive to aerosol histamine in vivo at three months of age when compared to sham immunised (AL(OH)3 + saline 1:3) or saline-treated rabbits for compliance measurements (P < 0.05). However, immunised rabbits although not significantly different to sham-immunised (P > 0.05) were significantly more responsive than saline-treated rabbits for resistance measurements (P < 0.05). Neonatal capsaicin treatment significantly attenuated the increased responsiveness seen in immunised rabbits for both compliance and resistance measurements (P < 0.05). The bronchial hyperresponsiveness is unlikely to be due to cellular infiltration per se as cell numbers assessed by bronchoalveolar lavage were not significantly different between groups (P > 0.05). Exogenous in vitro functional bronchial responses to capsaicin were increased in vehicle-immunised rabbits, an effect attenuated by neonatal capsaicin treatment (P < 0.05) whereas responses to methacholine, histamine or electrical field stimulation remained similar between groups (P > 0.05). Bronchial levels of calcitonin gene-related peptide- and substance P-like immunoreactivity were unaffected by any treatment (P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458398 TI - In situ hybridization reveals specific increases in G alpha s and G alpha o mRNA in discrete brain regions of morphine-tolerant rats. AB - In situ hybridization histochemistry has been used to detect the basal distribution of mRNA encoding the alpha subunit of Gs, Go and Gi2 proteins throughout the rat brain. Based on these data we investigated the effect of chronic morphine on the content of these G protein alpha subunits mRNA. We observed an increase in the expression of alpha s and alpha o messages of chronically morphine-treated animals, while no changes were seen in alpha i2 mRNA. Specifically a 30% increase in expression for alpha s was seen only in the paraventricular nucleus of hypothalamus and a 20% elevation for alpha o was detected in the claustrum and endopiriform nucleus. Immunoblotting analysis was used to correlate the changes in alpha s and alpha o messages with equivalent changes in protein levels. Chronic morphine significantly increased alpha s amounts in the hypothalamus (70%), and produced a minor elevation (30%) in G alpha o levels in the olfactory area. Our results indicate that in discrete brain regions altered G protein expression is part of the adaptive changes underlying opiate tolerance. PMID- 8458399 TI - Affinity of central adenosine A1 receptors is decreased in spontaneously hypertensive rats. AB - Functional defects in purinergic neurotransmission have been related to the development of arterial hypertension in spontaneously hypertensive rats. In order to elucidate the molecular basis of this perturbation, we have directly characterized adenosine A1 receptors using radioligand binding to rat brain membranes of Wistar Kyoto (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). Saturation studies with [3H]1,3-dipropylcyclopentylxanthine ([3H]DPCPX) showed a lower affinity in both 5- and 48-week-old SHRSP in comparison with age matched WKY. Similarly, competition experiments with [3H]DPCPX showed lower affinity of R-N6-phenylisopropyladenosine for the low-affinity binding site in 5- and 48-week-old SHRSP in comparison with WKY. In both studies, the difference in KD values was abolished by guanosine-5'-triphosphate in 5-week-old rats and mitigated in 48-week-old animals. No differences in Bmax values were observed in 5-week-old rats, whereas in 48-week-old SHRSP the number of receptors was significantly higher in comparison with age-matched WKY. Saturation experiments with the A1-selective agonist [3H]2-chloro-N6-cyclopentyladenosine ([3H]CCPA) demonstrated a higher affinity in 5-week-old SHRSP, whereas in 48-week-old hypertensive animals it was lower than in control WKY rats. No difference in receptor number was detected in comparison with age-matched WKY. In conclusion, our data demonstrated a diminished affinity of central adenosine A1 receptors for antagonists and for the low affinity state of the agonist binding site in genetically hypertensive rats. This might be due to structural changes of the receptor protein, to an altered G protein or defective receptor-G protein coupling in arterial hypertension. PMID- 8458400 TI - Neomycin blocks dihydropyridine-insensitive Ca2+ influx in bovine adrenal chromaffin cells. AB - There is evidence that bovine adrenal chromaffin cells are provided with both dihydropyridine-sensitive and -resistant voltage-sensitive Ca2+ influx pathways. Although recent electrophysiological work indicates that the dihydropyridine resistant pathway is partially mediated by omega-conotoxin-sensitive and insensitive Ca2+ channels, the pharmacological sensitivity of the latter channels remains elusive. We have now found that combined incubations with nitrendipine (1 microM) and neomycin (0.5 mM) reduced high K+ (50 mM)-evoked intracellular Ca2+ concentration ([Ca2+]i) transients to a larger extent than each drug separately. [Ca2+]i was measured using the fluorescent intracellular Ca2+ indicator fura-2. Neomycin (0.05-2 mM) reduced high K(+)-evoked 45Ca2+ uptake in a dose-dependent manner (IC50 = 0.09 mM). In the presence of nitrendipine (1 microM), the minimal neomycin concentration necessary for total blockade of 45Ca2+ uptake was reduced to 0.3 mM. Moreover, in the absence of nitrendipine the 45Ca2+ uptake remaining in 0.3 mM neomycin (26% of maximum) was similar to the fractional inhibition by nitrendipine alone (29%). Neomycin (0.05-2 mM) inhibited the [Ca2+]i transient induced by the L-type Ca2+ channel agonist Bay K 8644 (1 microM) much more extensively at 2 mM than at 0.3 mM (percent inhibition = 59% and 15%, respectively). Neomycin (0.05-2 mM) blocked high K(+)-evoked noradrenaline and adrenaline release in a dose-dependent fashion (IC50 = 0.8-1.1 mM), the blockade efficiency being enhanced in the presence of 1 microM nitrendipine (IC50 = 0.17 0.19 mM). It is concluded that neomycin (< or = 0.3 mM) blocks preferentially the dihydropyridine-insensitive Ca2+ influx pathway of the chromaffin cell. Moreover, both the dihydropyridine-sensitive and the dihydropyridine-resistant, neomycin sensitive Ca2+ influx pathways contribute strongly to depolarization-evoked catecholamine secretion. PMID- 8458401 TI - Dihydropyridine Ca2+ channel antagonists inhibit the salvage pathway for DNA synthesis in human vascular smooth muscle cells. AB - We examined the mechanisms by which Ca2+ channel antagonists inhibit the growth of smooth muscle cells by determining their effect on epidermal growth factor (EGF)-stimulated (i) induction of the early signalling gene, c-fos, (ii) incorporation of [3H]thymidine into cells as a measure of DNA synthesis, and (iii) increase in cell number. Verapamil, diltiazem, and the dihydropyridines felodipine, MDL 72892 A-15 (MDL) and nisoldipine had no effect on EGF-stimulated c-fos mRNA induction. Furthermore, only small inhibitory effects were observed on EGF-stimulated increases in cell number; felodipine, MDL, and nisoldipine at 0.3 microM inhibited EGF-stimulated cell proliferation by 9, 11, and 15%, respectively. In contrast, the dihydropyridine Ca2+ channel antagonists were found to be potent inhibitors of [3H]thymidine incorporation suggesting that they inhibit DNA synthesis. However, further examination revealed that the potent effects of dihydropyridine Ca2+ channel antagonists on [3H]thymidine incorporation were due not to an effect on incorporation of [3H]thymidine into DNA, but to a marked inhibitory effect on the cellular uptake of [3H]thymidine. Thus, we conclude that the small antiproliferative effects of the dihydropyridine antagonists are predominantly due to their ability to inhibit the activity of the salvage pathway for thymidylate synthesis in human vascular smooth muscle cells. PMID- 8458402 TI - Activation by KRN2391 and nicorandil of glibenclamide-sensitive K+ channels in Xenopus oocytes. AB - KRN2391 (N-cyano-N'-(2-nitroxyethyl)-3-pyridine-carboximidamide methanesulfonate) and nicorandil, a new class of K+ channel openers, each with an NO2 moiety, induced outward K+ currents in follicle-enclosed Xenopus oocytes. These K+ currents were suppressed concentration-dependently and reversibly by glibenclamide, phentolamine and trifluoperazine, all known to inhibit ATP sensitive K+ channels. The nicorandil-induced K+ current was virtually abolished by defolliculation of oocytes, while the KRN2391 response was little affected by defolliculation. These results suggest that Xenopus oocyte has at least two types of glibenclamide-sensitive K+ channels, one is selectively sensitive to KRN2391 and is probably localized in the oocyte, and the other is sensitive to nicorandil and distributed in the follicle cells surrounding an oocyte. PMID- 8458403 TI - Opposing actions of an adenosine A2 receptor agonist and a GTP analogue on the regulation of dopamine D2 receptors in rat neostriatal membranes. AB - We have previously found, in rat striatal membrane preparations, that stimulation of adenosine A2 receptors (with the selective adenosine A2 receptor agonist CGS 21680) increases the high- and low-affinity dissociation constants and increases the proportion of high-affinity dopamine D2 receptor binding sites labelled with the selective dopamine D2 receptor antagonist [3H]raclopride. As guanine nucleotides and divalent cations (such as Mg2+) are known to regulate the proportion of high-affinity D2 receptor binding sites in opposing ways, interaction experiments with CGS 21680, the GTP analogue Gpp(NH)p and MgCl2 were performed. Our results suggest that these three factors exert significant, though independent, effects on the proportion of high affinity D2 receptors, and that A2 receptors regulate both the affinity of D2 receptors and the transduction of the signal from the D2 receptor to the G-protein. PMID- 8458404 TI - Upregulation of forebrain proenkephalin mRNA subsequent to NMDA receptor blockade. AB - Blockade of NMDA (N-methyl-D-aspartate) receptors for 5 h with MK 801 resulted in elevated levels of proenkephalin mRNA (up to 40% above vehicle-injected controls) in medial and anterior aspects of the caudate-putamen (mCPU and aCPU) and the nucleus accumbens (NAc). Increases were dose-dependent, with maximal effect at 0.1 mg/kg (body weight). These results suggest that NMDA receptor activity exerts tonic inhibition on proenkephalin mRNA expression in the striatum and accumbens of the rat brain. PMID- 8458405 TI - Nature in the laboratory--nature as a laboratory. Considerations about the ethics of release experiments. AB - Field tests with genetically modified organisms go beyond the boundaries of the politically and morally neutralized space that normally surrounds scientific experiments. They enter public areas. As a social process of shaping nature they are political in a fundamental sense. Consequences of this observation concern the legitimacy of decisions and the legitimacy of deciding procedures. The political rights of citizens and their human rights can only be respected if these procedures are democratic. Without a more serious exploration of the specific circumstances of release tests--for example, the precise ecological context, the consequences for the future development of the affected ecosystem, the social consequences, and the possible institutional ways of establishing gene technology in agriculture--we do not really know what we are doing when we release transgenic organisms. Moral judgements today can therefore only be prima facie, not free from shortcomings. As responsible judges we must confess that we are still morally blind. PMID- 8458406 TI - Evaluating the fate of genetically modified microorganisms in the environment: are they inherently less fit? AB - Genetically modified microorganisms hold great promise for environmental applications. Nonetheless, some may have unintended adverse effects. Of particular concern for risk assessment is the simple fact that microorganisms are self-replicating entities, so that it may be impossible to control an adverse effect simply by discontinuing further releases of the organism. It has been suggested, however, that genetically modified microorganisms will be poor competitors and therefore unable to persist in the wild due to energetic inefficiency, disruption of genomic coadaptation, or domestication. Many studies support the hypothesis that genetically modified microorganisms are less fit than their progenitors, but there are a few noteworthy counter-examples in which genetic modifications unexpectedly enhance competitive fitness. Furthermore, subsequent evolution may eliminate the maladaptive effects of some genes, increasing the likelihood that a modified organism or its engineered genes will persist. Evaluating the likelihood that a genetically modified microorganism or its engineered genes will persist is a complex ecological and evolutionary problem. Therefore, an efficient regulatory framework would require such evaluations only when there are plausible scenarios for significant adverse environmental effects. PMID- 8458407 TI - The true meaning of 'exotic species' as a model for genetically engineered organisms. AB - The exotic or non-indigenous species model for deliberately introduced genetically engineered organisms (GEOs) has often been misunderstood or misrepresented. Yet proper comparisons of of ecologically competent GEOs to the patterns of adaptation of introduced species have been highly useful among scientists in attempting to determine how to apply biological theory to specific GEO risk issues, and in attempting to define the probabilities and scale of ecological risks with GEOs. In truth, the model predicts that most projects may be environmentally safe, but a significant minority may be very risky. The model includes a history of institutional follies that also should remind workers of the danger of oversimplifying biological issues, and warn against repeating the sorts of professional misjudgements that have too often been made in introducing organisms to new settings. We once expected that the non-indigenous species model would be refined by more analysis of species eruptions, ecological genetics, and the biology of select GEOs themselves, as outlined. But there has been political resistance to the effective regulation of GEOs, and a bureaucratic tendency to focus research agendas on narrow data collection. Thus there has been too little promotion by responsible agencies of studies to provide the broad conceptual base for truly science-based regulation. In its presently unrefined state, the non indigenous species comparison would overestimate the risks of GEOs if it were (mis)applied to genetically disrupted, ecologically crippled GEOs, but in some cases of wild-type organisms with novel engineered traits, it could greatly underestimate the risks. Further analysis is urgently needed. PMID- 8458408 TI - Lack of effect of antioxidant therapy during renal ischemia and reperfusion in dogs. AB - Acute ischemic renal failure is of great clinical importance because of its frequent occurrence and the high mortality it causes. Recent observations indicate that reperfusion has its own dangers because of oxygen-derived free radicals. To study this problem, ischemia was evoked in dogs in one kidney, by clamping the left renal artery for 45 min. This was followed by a 90-min period of reperfusion when diuresis, GFR, PAH clearance and sodium and potassium excretion were studied. Besides a control group (n = 6), the following treatment groups were investigated. Allopurinol (n = 7): 50 mg/kg for two days p.o. and 50 mg/kg in physiological saline infusion during the experiment; a small dose of SOD (n = 6): 0.5 mg/kg in infusion, started 1 min before reperfusion and given continuously for 10 min; and a high dose of SOD (n = 7): 5 mg/kg as above. In the first 15 min following reperfusion, the renal functions significantly worsened in all groups. Later on, the renal functions gradually improved and in the last period after reperfusion, GFR in the ischemic kidney was 64%, cPAH 59%, diuresis 60% and sodium and potassium excretion were 65% and 76%, respectively, of the basal values in the control group. Treatment with free radical scavengers did not cause any considerable changes in the renal functions. In some respects, the worst results were observed with low-level SOD treatment (cPAH, diuresis, as well as sodium and potassium excretion). At the end of reperfusion, there was a significant drop in sodium excretion by the right (intact circulation) kidney of the treated animals. PMID- 8458409 TI - Lack of effects of 5-HT3 antagonists on normal and morphine-attenuated sexual behaviours in female and male rats. AB - Although 5-HT1 and 5-HT2 receptor activity is known to influence copulation, the effects of 5-HT3 receptor-selective drugs on sexual activity have yet to be systematically studied. The following experiments investigated the effects of the 5-HT3-selective antagonists MDL 72222, ondansetron and ICS 205-930 on female sexual behaviour; male rats were studied using ondansetron and granisetron. These compounds influenced neither male nor female copulatory behaviours, suggesting that 5-HT3 receptors contribute little to the modulation of sexual activity. 5 HT3 receptor antagonists block certain opioid-induced behaviours and opioids selectively inhibit sexual behaviours; therefore, the ability of ondansetron and ICS 205-930 to modify morphine-attenuated copulatory activity was also tested. While morphine inhibited copulation, 5-HT3 antagonists failed to reverse the effects. PMID- 8458410 TI - Systems analysis in cell biology: from the phenomenological description towards a computer model of the intracellular signal transduction network. AB - In this paper we introduce a systematic approach for the modelling of complex biological systems which is especially useful for the analysis of signal transduction mechanisms in cell biology. It is shown that systems analysis in form of top-down levelled dataflow diagrams provides a powerful tool for the mathematical modelling of the system in terms of a stochastic formulation. Due to the exact formulation, the consistency of the model with the experimental results can be tested by means of a computer simulation. The method termed Structured Biological Modelling (SBM) is illustrated by modelling some aspects of the second messenger network which regulates cell proliferation. As an example for the straightforward development of a mathematical description a stochastic computer model for intracellular Ca2+ oscillations is presented. PMID- 8458411 TI - Chromosomal abnormalities in starved and marginally malnourished rats and in utero upon rehabilitation. AB - The effects of starvation and marginal malnutrition (MN) on the lymphocytes of rats were evaluated by chromosomal analysis before and after rehabilitation. The effect of parental starvation or malnutrition on chromosomal aberrations in the foetus was also studied. Wistar rats, 30-35 days old, were starved for 5 days or fed a minimally restricted or a severely restricted diet for three weeks. At the end of the period of starvation or malnutrition, lymphocytes were isolated and chromosomal analysis was performed. Starved and severely restricted rats showed significantly higher mean chromosomal aberrations than the controls. These aberrations returned to a normal level when the experimental groups were rehabilitated for a month, indicating that the damage was transient. A chromosomal aberration study done on foetal cells from rehabilitated rats which had previously been starved or fed a severely restricted diet showed significantly increased values, indicating that some damage was permanent. A low number of implantations was also recorded in these experimental groups. These observations clearly indicate that young animals exposed to conditions like starvation or chronic malnutrition are prone to permanent damage of the genetic system. PMID- 8458412 TI - Expression of alpha, beta A and beta B subunits of inhibin or activin and follistatin in rat pancreatic islets. AB - We first detected the mRNA expression of follistatin and three subunits of inhibin/activin in rat pancreatic islets by reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemistry using anti-follistatin serum (against residues 123-134) revealed that follistatin was localized only in insulin-producing B cells. Although the beta A subunit was detectable in the islets, the immunostainable cell types were completely different with two beta A antisera, i.e. anti-beta A (1-10)-Tyr stained B cells, while anti-beta A (87-99) stained glucagon-producing A cells. This inconsistent immunoreactivity was probably related to follistatin binding to beta subunits of inhibin/activin. This study indicates that follistatin and inhibin/activin in the islet serve as paracrine or autocrine modulators in the endocrine pancreas. PMID- 8458413 TI - Inhibition of passive sensitization of human peripheral basophils by synthetic human immunoglobulin E peptide fragments. AB - To delineate the binding site in the human immunoglobulin E (IgE) molecule to the Fc epsilon receptor on basophils and mast cells, we chemically synthesized a total of 71 peptide fragments within the sequence Ser300-Lys547 in the human IgE molecule. The synthetic peptides were tested for their capacity to inhibit passive sensitization of human peripheral basophils with atopic patient's serum containing the specific IgE against dust mites in vitro. It was found that a peptide fragment, Pro345-Ile356, potently inhibited the passive sensitization. To clarify the minimal active core, various analogues, such as shortened, substituted (by Gly or Ala residue), omission and retro-sequence peptides, were synthesized and assayed. The results suggested that the sequence Pro345-Lys352 in the human IgE molecule would be an IgE binding site, and that a synthetic octapeptide, Pro345-Phe-Asp-Leu-Phe-Ile-Arg-Lys352, inhibited the passive sensitization, probably by occupying the Fc epsilon receptor sites on the cells. PMID- 8458414 TI - External pH regulates the slowly activating potassium current IsK expressed in Xenopus oocytes. AB - A slowly activating, delayed rectifier potassium current, IsK, was expressed in Xenopus laevis oocytes by injection of cRNA transcribed from a rat kidney cDNA clone. External acidification reversibly decreased the current amplitude. The effects were concentration dependent on protons with Kd at pH approximately 5.5 and a Hill coefficient of 1.0. External acidification reduced the maximal conductance (Gmax) without affecting the activation kinetics; this effect was not dependent on membrane voltages. These data suggest that H+ ions bind to the channel with a one-to-one stoichiometry, and this binding site may be located outside of the membrane electric field. PMID- 8458415 TI - Purification of macrophage migration inhibitory factor (MIF) from bovine brain cytosol. AB - Two isoforms of the macrophage migration inhibitory factor (MIF) have been isolated to homogeneity from bovine brain cytosol. In agreement with the cDNA sequence of their human counterpart, they both have an apparent molecular weight of 12 kDa and are characterized by the following N-terminal amino acid sequence NH2-PMFVVNTNVPRASVPDGLLSELTQQLAQATGKPPQYIAV-. CD spectra revealed that bovine MIF contains 42% (+/- 3%) alpha-helix and 21% (+/- 3%) beta-structure. CD-constrained prediction of the secondary structure assigned MIF to the alpha/beta-class of proteins. PMID- 8458416 TI - Activation of adenylate cyclase in cdc25 mutants of Saccharomyces cerevisiae. AB - The activation of adenylate cyclase by guanine nucleotides and 6-deoxyglucose was studied in membrane preparations from S. cerevisiae mutants lacking the CDC25 gene product. Adenylate cyclase from cdc25 ts membranes was activated by GTP and GppNHp in membranes from cells collected after glucose was exhausted from the medium. The activation was also observed in membranes from repressed cells at 2.5 mM Mg2+. It is also shown that 6-deoxyglucose can activate adenylate cyclase in the absence of CDC25 gene product. The relative amount of membrane-bound adenylate cyclase was drastically reduced in cdc25 ts membranes when subjected to the restrictive temperature, while no significant change was observed in the wild type. These data suggest that Cdc25 might not be required in certain conditions for the guanine nucleotide exchange reaction in Ras and that it might be implicated in anchoring the Ras/adenylate cyclase system to the plasma membrane. PMID- 8458417 TI - Decorin is specifically solubilized by heparin from the extracellular matrix of rat skeletal muscles. AB - We have previously communicated that heparin co-solubilizes the asymmetric form of acetylcholinesterase (AChE) and a dermatan sulfate proteoglycan from the extracellular matrix (ECM) of rat skeletal muscles. In this report we unequivocally demonstrate by biochemical and immunological analyses that the proteoglycan that is solubilized by heparin from rat skeletal muscle ECM corresponds to decorin. These results support the concept for the role of decorin in the ECM organization. PMID- 8458418 TI - Peptide aldehydes as inhibitors of HIV protease. AB - We have recently shown that alpha-MAPI, a peptidic aldehyde of microbial origin, inhibits the HIV protease with a potency comparable to pepstatin, having, differently from pepstatin, no activity on other aspartic proteases. In this study different peptide derivatives containing a C-terminal aldehyde have been tested to assess the potential of this function for the inhibition of HIV protease. The results of our analysis correspond with the recently published subsite preferences of the viral enzyme, indicating that aldehydes bind to the active site of the HIV protease. Our data suggest that peptide aldehydes can act in their hydrated forms as transition state analogues with the most potent inhibitor having an IC50 of 0.9 microM. PMID- 8458419 TI - Synechocystis 6803 plastocyanin isolated from both the cyanobacterium and E. coli transformed cells are identical. AB - Native plastocyanin from Synechocystis 6803 has been isolated and purified to electrophoretic homogeneity. The corresponding gene (petE) has been cloned and expressed in E. coli, thus leading to a protein completely identical to plastocyanin purified from the cyanobacterial cells. The petE gene product is correctly processed in E. coli as deduced from the N-terminal amino acid sequences. These results, along with the identical physicochemical and kinetic properties of the two protein preparations, confirm that expression of petE in E. coli is an adequate tool to address the study of Synechocystis plastocyanin by site-directed mutagenesis. PMID- 8458420 TI - Unusual kinetic behavior predicted for alpha-keto acid dehydrogenase complexes. AB - A novel regulation type, which may be observed as an unusual kinetic 'cooperativity', is predicted for the alpha-keto acid dehydrogenase complexes. The inter-relationship of this regulation with the well-known regulatory effect of enzyme phosphorylation is discussed. PMID- 8458421 TI - Expression of c-jun/AP-1 during myogenic differentiation in mouse C2C12 myoblasts. AB - Mitogen withdrawal triggers myogenic differentiation in skeletal myoblasts in culture. We have examined the expression of the proto-oncogene c-jun during this process in mouse C2C12 myoblasts. c-jun belongs to a family of immediate early genes whose expression is activated in cultured cells in response to the addition of serum growth factors. Interestingly, expression of c-jun was maintained in mouse C2C12 and rat L6 myoblasts undergoing myogenic differentiation under low serum conditions. Previously it has been reported that expression of c-jun is downregulated during differentiation of C2 cells. However, our results using C2C12 cells, a subclone of the C2 line, show that c-jun mRNA, protein and the activator-protein 1 (AP-1) DNA-binding activity were easily detected in proliferating myoblasts and differentiated myotubes. Although overexpression of c jun has been shown to block myogenic differentiation in C2 cells, results presented here suggest that expression of c-jun at physiological levels may not interfere with skeletal myogenesis. PMID- 8458422 TI - Interaction of lactogenic hormones with purified recombinant extracellular domain of rabbit prolactin receptor expressed in insect cells. AB - The extracellular domain of rabbit prolactin receptor (rbPRLR-ECD) expressed in an insect/baculovirus expression system was purified by affinity chromatography on immobilized PRL followed by gel filtration. The purified protein was over 90% homogeneous as indicated by SDS-PAGE in the presence or absence of reducing agent, and by chromatography on a Superdex column. Its molecular mass determined by SDS-PAGE was 32 kDa, and by gel filtration, 27 kDa. Both values are higher than the 22.8 kDa deduced from the cDNA sequence, indicating extensive glycosylation. The Ka value for interaction with ovine (o) PRL was 25.4 nM-1, but even at high rbPRLR-ECD:hormone molar ratios, the stoichiometry of interaction with oPRL or human growth hormone indicated formation of only 1:1 complexes, in contrast to human growth hormone (hGH)-ECD which forms 2:1 complexes with hGH. PMID- 8458423 TI - Primary structure determination of mono- and diacylglycerol lipase from Penicillium camembertii. AB - The complete amino acid sequence of mono- and diacylglycerol lipase from Penicillium camembertii was determined. This lipase has a single polypeptide chain consisting of 276 amino acid residues with two disulfide linkages. The primary structure was revealed by sequencing the digests of the intact and S pyridylethylated proteins by trypsin, endoproteinase Lys-C and V8 protease. The two-dimensional electrophoresis was also carried out to confirm the internal sequence. The catalytic triad of this lipase was Ser, Asp and His, and one potential N-glycosylation site was also revealed. PMID- 8458424 TI - Kinetic mechanism of ketoreductase activity of prostaglandin F synthase from bovine lung. AB - The kinetic mechanism of ketoreductase activity of bovine lung prostaglandin F synthase, expressed in E. coli, was investigated. Data on initial velocity and radioisotope exchange between [3H]prostaglandin D2 and 9 alpha,11 beta prostaglandin F2 suggest that the enzyme obeys the ping-pong mechanism. Using a fluorescence technique we obtained a binding constant of 3 microM for NADPH. This is in close correlation with the kinetically determined intrinsic Michaelis constant for NADPH. Activation energy of the redox process was determined from the temperature dependence of maximal velocities for nitrobenzaldehyde and menadione and was found to be 119 and 96 kJ/mol, respectively. PMID- 8458425 TI - Three-dimensional structure of neurotoxin-1 from Naja naja oxiana venom at 1.9 A resolution. AB - Neurotoxin-1 from Naja naja oxiana venom (NTX-1) has been crystallized by vapor diffusion in sitting drops. The crystals have cell dimensions of a = 25.2 A, b = 75.6 A, c = 35.9 A, and are in space group P2(1)2(1)2(1). Three-dimensional data to 1.9 A have been recorded by a Syntex P2(1) automatic diffractometer. The atomic structure of the toxin has been determined by molecular replacement using the alpha-cobratoxin (alpha-CTX) as the search model. The position of 534 non hydrogen protein atoms have been determined. The model contains 65 water molecules. Refinement has led to an R-factor of 19.3% at 1.9 A resolution. The secondary and tertiary structures of NTX-1 have been analyzed and a comparison with structure of the alpha-CTX has been made. PMID- 8458426 TI - Interaction of carbonyl cyanide m-chlorophenylhydrazone with the photosystem II acceptor side. AB - We show that CCCP, known as an uncoupler of photophosphorylation and an ADRY agent, inhibits FeCy photoreduction and coupled O2 evolution by isolated chloroplasts equally (I50 approximately 2 microM), but is practically without effect on the O2 evolution coupled with SiMo reduction within the 0.2-10 microM concentration range. CCCP has no effect on the nanosecond chlorophyll fluorescence in chloroplasts incubated at low light intensity, but decreases it at high light intensity. The electron transfer from reduced TMPD or duroquinol to methylviologen is resistant to CCCP. The efficiency of the CCCP inhibitory action on the FeCy photoreduction depends on the rate of electron flow, which is controlled by the light intensity. The data obtained show that CCCP is oxidized by the photosystem II donor side and is reduced by QP, competing for electrons with FeCy and the cytochrome blf complex. PMID- 8458428 TI - Precise mapping and molecular characterization of the MFT1 gene involved in import of a fusion protein into mitochondria in Saccharomyces cerevisiae. AB - Garrett et al. [Mol. Gen. Genet. 225 (1991) 483-491] recently reported that an Atp2-lacZ fusion protein was transported into mitochondria in yeast, thus identifying the MFT1 (mitochondrial fusion targeting) gene as a genomic fragment which complements a mutation (mft1) that failed in targeting a fusion protein into mitochondria. They mapped this gene to the ORF, which we have independently identified as a gene homologous to the cyc07 gene, which is expressed specifically in the S phase during the plant cell cycle. We have mapped the MFT1 gene precisely and found that this gene should correspond to the neighboring ORF, rather than the ORF they identified. PMID- 8458427 TI - Molecular cloning of a mouse myosin I expressed in brain. AB - We have isolated two cDNAs that encode putative myosin I heavy chains by polymerase chain reaction amplification of brain cDNA with degenerate oligodeoxynucleotide primers representing myosin I-specific conserved amino acid sequences. We report the complete deduced amino acid sequence of one of these cDNAs. The sequences is most similar to those of the avian and bovine brush border myosin Is, with five putative calmodulin-binding repeats at the head-tail junction. Northern analysis demonstrates that this myosin heavy chain, unlike the brush border myosins, is expressed in many tissues. PMID- 8458429 TI - Expression and characterization of human D4 dopamine receptors in baculovirus infected insect cells. AB - The human D4 dopamine receptor has been genetically engineered for expression in insect cells using the baculovirus system. A D4 cDNA gene fusion construct [(1991) Nature 350, 610-614] was synthetically modified to remove two introns from the coding region, and expressed in S. frugiperda (Sf9) cells as a fusion with a short sequence from the polyhedrin protein. Binding assays with [3H]spiperone indicated high levels of D4 receptor binding 90 h after infection and a pharmacological profile identical to that reported for D4 receptors expressed in COS-7 cells using the cDNA gene hybrid. We also show that the agonist binding affinity of D4 receptors expressed in Sf9 cells can be shifted by GTP-gamma-S, indicating coupling to G-proteins. PMID- 8458430 TI - Ca2+ binding of latent transforming growth factor-beta 1 binding protein. AB - Latent transforming growth factor-beta 1 binding protein (LTBP) is a constituent of the latent high molecular weight complex of TGF-beta 1 in human platelets. In the present communication, we show that LTBP binds Ca2+ in its free form as well as in the latent TGF-beta 1 complex. The binding of Ca2+ induces a structural change which protects the molecule against proteolysis and changes its elution position when analyzed by anion exchange chromatography. The in vitro activation of TGF-beta 1 is not influenced by the presence of Ca2+. The possible significance of Ca2+ binding of LTBP is discussed. PMID- 8458431 TI - Sequence similarity of a hornet (D. maculata) venom allergen phospholipase A1 with mammalian lipases. AB - We have determined the sequence of a venom allergen phospholipase A1 from white faced hornet (Dolichovespula maculata) by cDNA and protein sequencings. This protein of 300 amino acid residues (Dol m I) has no sequence similarity with other known phospholipases. But it has sequence similarity with mammalian lipases; about 40% identity in overlaps of 123 residues. Tests suggest that hornet phospholipase has weak lipase activity. Hornet venom has 3 major allergens, and another hornet allergen antigen 5 (Dol m V) was previously found to have sequence similarity with a mammalian testis protein and a plant leaf protein. PMID- 8458432 TI - Trans-activation of the murine dystrophin gene in human-mouse hybrid myotubes. AB - Myotube cultures of the myogenic cell line, C2, produce significantly lower levels of dystrophin than primary mouse cultures. We demonstrate that expression of the C2 dystrophin gene increases 10-fold in hybrid myotubes formed by fusion of C2 and dystrophin-deficient human myoblasts from a Duchenne muscular dystrophy patient. These results indicate that C2 cells are deficient in endogenous gene regulatory factors which enhance dystrophin expression, and that the C2 cell line may therefore be used to identify putative trans-acting factors involved in the regulation of dystrophin gene expression. PMID- 8458433 TI - Endothelin-converting enzyme activity in human serum lipoprotein fraction. AB - Endothelin-1 (ET-1)-converting enzyme (ECE) activity in the human serum lipoprotein fraction was studied using a sensitive enzyme immunoassay and reverse phase high performance liquid chromatography. The ECE activity of cleaving synthetic human big ET-1 into ET-1 by the serum lipoprotein fraction was about 14 times greater than that by whole serum, and the activity was closely associated with lipoprotein itself. The lipoprotein ECE activity, which was optimal at pH 7.0, was inhibited by EDTA, o-phenanthroline, phosphoramidon, thiorphan, phenylmethanesulfonyl fluoride and chymostatin, but not by cysteine or aspartic proteinase inhibitors, suggesting metalloproteinase- and chymotrypsin-like properties. These results suggest that the serum lipoprotein ECE may be involved in the processing of big ET-1 to ET-1 in the circulatory system. PMID- 8458435 TI - Sucrose synthase genes in barley. cDNA cloning of the Ss2 type and tissue specific expression of Ss1 and Ss2. AB - A cDNA of 2,708 bp encoding type 2 sucrose synthase (Ss2) from barley has been sequenced. Similarity of this cDNA with respect to that of type 1 (Ss1) is high in the coding region (75% identical positions), but low (41% identical residues) in the 3' non-coding region. Type-specific non cross-hybridizing probes for Northern blot analysis have been obtained from the 3' ends. The Ss1 type is highly expressed in developing endosperm and in roots and, at lower levels, in coleoptiles and aleurone. The Ss2 mRNA is abundant in endosperm, low in aleurone, and undetected in coleoptiles and roots. PMID- 8458434 TI - Isolation of a novel substrate-competitive tyrosine kinase inhibitor, desmal, from the plant Desmos chinensis. AB - In the course of a screening program for tyrosine kinase inhibitors, the chloroform extract of a tropical plant, Desmos chinensis, strongly inhibited the enzyme activity. The active substance was purified by silica gel, gel filtration, and finally crystallized. The structure was elucidated by mass spectrometry and X ray crystallography to be 8-formyl-2,5,7-trihydroxy-6- methylflavanone, and we named it desmal. Desmal competed with peptide substrate and non-competed with ATP. It inhibited tyrosine kinase in situ in epidermal growth factor (EGF) receptor-overexpressing NIH3T3 (ER12) cells. It also inhibited EGF-induced inositol phosphate formation and morphological changes. PMID- 8458436 TI - Reduced influx is a factor in accounting for reduced vincristine accumulation in certain verapamil-hypersensitive multidrug-resistant CHO cell lines. AB - The rates of accumulation, influx and efflux of vincristine have been examined in a series of multidrug-resistant Chinese hamster ovary cell lines which show exceptionally high levels of hypersensitivity (collateral sensitivity) to several resistance modifiers. The more highly resistant members of the series show significantly reduced levels of vincristine influx compared to the control cell line from which they were derived. It is possible that resistance modifier hypersensitivity and reduced vincristine influx may be due to a common change in membrane composition which has arisen during prolonged selection for vincristine resistance in these cell lines. PMID- 8458437 TI - Assignment of the ligand binding site of the porcine estradiol receptor to the N terminal 17 kDa part of domain E. AB - Ligand-filled porcine estradiol receptor was adsorbed to heparin-Sepharose, from which a 26 kDa fragment was released by papain. Its mass was reduced to a 17 kDa fragment by trypsin. The sedimentation velocities of both estradiol binding fragments increased after reaction with the MAB 13H2. The same antibody identified the denatured fragments on Western blots. The N-terminal 21 amino acid sequence was obtained from the 17 kDa peptide which corresponds to amino acids 303-323 of the human receptor with four amino acids exchanged. This indicates that the ligand binding site resides in the N-terminal 17 kDa portion of domain E. PMID- 8458438 TI - Characterization of the linker peptide of the single-chain Fv fragment of an antibody by NMR spectroscopy. AB - A comparison of the single-chain Fv fragment of the antibody McPC603 (scFv) with its corresponding unlinked Fv fragment has been carried out with 15N-edited NMR spectroscopy. The two Fv fragments adopt the same structure, indicating that the linker does not perturb the folding of the domains. This also directly demonstrates that folding in vivo (Fv fragment) and in vitro (scFv fragment) leads to the same structure. The main differences in the spectra of the uniformly 15N-labeled scFv and Fv fragments are due to signals of Gly and Ser from the linker peptide of the scFv fragment. The linker peptide has been mapped with NMR spectra of 15N-glycine- and 15N-glycine/15N-serine-labeled scFv fragments. The 15N T2 relaxation data indicate that the linker peptide is more flexible than the rest of the molecule. PMID- 8458439 TI - Prediction of cerebral ischaemia using loco-regional anaesthesia. AB - The authors present their experience in cerebral monitoring during carotid surgery by surveillance of the clinical status of the patients. The operation was performed using loco-regional anaesthesia and employing a temporary shunt in those cases with cerebral ischaemic symptoms at clamping. In the 212 operations performed, no complication due to inadequate monitoring or complications related to coronary disease or respiratory insufficiency were observed. PMID- 8458440 TI - Intraoperative cerebral monitoring in carotid surgery. AB - We have used and studied intraoperative cerebral monitoring in order to prevent intraoperative and early postoperative cerebral ischaemia. The techniques examined have included stump pressure measurement, the evaluation of somatosensory evoked potentials (SEPs) and completion intraoperative angiography. Stump pressure was measured in 920 patients and a safety level of 50 mmHg confirmed. Below this value, non-shunted patients were three times more likely to have cerebrovascular accident (CVA). SEPs were prospectively monitored in 72 patients and a mean decrease of N20-P25 in complex amplitude was seen in patients with a positive CT scan. In particular, pathological SEPs were found in 53% of patients with a positive CT scan, and in 54% of those with a contralateral carotid occlusion. In these patients, the N20-P25 amplitude fell progressively in the first 4 min. Using SEPs, the indication for shunting was 42% lower than with the measurement of back pressure and no patient with normal SEPs had a postoperative neurological deficit. The data obtained under local anaesthesia in 25 patients monitored by stump pressure and SEPs did not give better results. Intraoperative completion angiography performed routinely since 1978 has made it possible to reduce the need for immediate reoperation from 10-2%. PMID- 8458441 TI - Preoperative prediction of cerebral ischaemia due to carotid occlusion. PMID- 8458442 TI - Urgent carotid surgery for high risk patients. AB - Carotid surgery was performed urgently on 22 occasions out of 300 (7%). Of 15 patients with progressing stroke, in all, progression of stroke was arrested. Six patients recovered virtually completely and eight had improving neurological deficit after surgery, i.e. 14 of 15 (93%) benefitted. The other patient had arrest of stroke for a week and then suffered ipsilateral stroke. Of the seven patients operated upon for crescendo transient ischaemic attacks, five had no deficit after surgery or further attacks. The sixth patient had no further attacks but was found to have a tiny, neurological deficit. In these six patients (87%), surgery was greatly beneficial. The remaining patient had a fatal stroke following operation. PMID- 8458443 TI - The selection for shunting in patients with severe bilateral carotid lesions. AB - Patients with severe bilateral carotid lesions (stenosis and contralateral internal carotid occlusion) are at high risk of having a stroke, and carotid endarterectomy has been proposed as the best treatment. In spite of improvements in surgical technique, this operation is still associated with significant perioperative complications (5-13%) which are frequently (up to 40%) correlated with intolerance to internal carotid artery clamping. For this reason, intraoperative cerebral monitoring able to accurately detect ischaemia during surgery would be useful. Reviewing our experience from the last 7 years in 74 patients operated on for stenosis and contralateral occlusion of the internal carotid artery, we found a 1.3% neurological morbidity and 1.3% mortality rate. Presenting symptoms included focal transient ischaemia attacks (TIAs) in 57 patients, stroke in 16 patients and two patients were asymptomatic. Half of these patients (37) were operated on under general anaesthesia with electroencephalogram (EEG) monitoring, stump pressure measurement and selective shunting. In this group, two patients (5.4%) sustained a postoperative stroke, one of which was fatal. The remaining 37 patients were operated on under local regional anaesthesia with selective shunting on the basis of neurological deficit onset or loss of consciousness during the test clamp. There were no postoperative neurological complications in this group but one patient died of acute myocardial infarction on the 6th postoperative day. This experience suggests that it is possible to perform carotid endarterectomy in patients with severe bilateral lesions with a postoperative complication rate similar to that in patients with less complicated obstructive lesions if accurate intraoperative cerebral monitoring is used. PMID- 8458444 TI - Cerebral haemodynamics during carotid cross-clamping. AB - Carotid artery cross-clamping ischaemia during carotid endarterectomy (CEA) causes 5-30% of perioperative neurological deficits. This study was performed to identify possible clinical situations at higher risk for carotid cross-clamping ischaemia. 606 consecutive patients underwent CEA and were retrospectively studied; they were grouped according to risk factors, presence of associated vascular diseases, clinical pattern, angiographic and CT scan findings. Stump pressure measurement was provided in all patients, perioperative monitoring during CEA was performed by electroencephalogram (EEG) in 469 (77%) and somatosensorial evoked potentials (SEP) in 137 (23%). Local anaesthesia was used in 88 (14.5%) patients. Ischaemic changes during carotid cross-clamping were registered in 118 patients (19.5%). The incidence of cross-clamping ischaemia was then related to different factors; it affected 5.6% of asymptomatics, 25.4% of patients with fixed stroke and 38.5% of those with stenosis and contralateral occlusion. Angiographic and clinical correlation showed that patients with more severe lesions are mostly affected by clamping ischaemia (up to 55% in those with stroke and stenosis with contralateral occlusion). Age, hypertension and diabetes do not significantly affect incidence of ischaemic changes. Positive CT scan increased this risk; statistical relevance was found in regard to patients with unilateral or bilateral stenosis and in those with transient ischaemic attacks. A higher risk can be expected for subjects with more severe clinical and instrumental findings, even if no patients can be considered completely at risk or risk free. Perioperative monitoring is always mandatory and is of great importance in detecting ischaemic changes and preventing cerebral damage using a temporary intraluminal shunt. PMID- 8458445 TI - Cerebral monitoring during carotid surgery. PMID- 8458446 TI - Laparoscopic surgery for ectopic pregnancies: technology assessment and public health implications. AB - OBJECTIVES: To review the process by which technology is assessed in the United States and to use the principles elicited to compare laparotomy versus laparoscopy for the treatment of ectopic pregnancies (EPs). PARTICIPANTS: Patients with an EP documented in 1987 in the United States. METHODS: Determining and reviewing the applicability, safety, efficacy, cost-effectiveness, cost benefit, and availability of laparoscopic surgery for an EP. RESULTS: Laparoscopic surgery is applicable to at least 80% of patients, representing some 70,400 women in 1987. Safety and efficacy of laparoscopy are comparable with laparotomy, with the exception of a possible increase in the frequency of persistent EPs, if a conservative procedure is performed endoscopically. Dollar for dollar laparoscopy is more cost-effective than laparotomy for the treatment of EPs, with reduced hospitalization and recovery time, and improved cosmesis. Cost-benefit analysis indicates a savings of $105,600,000.00 in direct hospitalization costs and $65,000,000.00 in increased employer or patient income, because of a more rapid return to work time. Furthermore, savings in decreased home care requirements could not be calculated. The use of laparoscopic surgery in all potential candidates with an EP in 1987 would have resulted in an increased expenditure of $28,160,000.00 annually for additional equipment and $3,520,000.00 for the repeat laparotomies required to treat the excess number of persistent EPs. The expense of training physicians and operating room staffs in this technique could not be quantified. Overall, availability of this procedure was felt to be considerably less than 30% of affected patients. CONCLUSIONS: Overall, the use of laparoscopic surgery in all eligible (> or = 80%) patients with an EP in 1987 in the United States would have resulted in a savings of approximately $138,920,000.00 for that year alone. Currently, there is a tremendous deficiency in the availability of this cost-effective procedure, contributing to the escalating costs of medical care. PMID- 8458447 TI - Hysteroscopic metroplasty in the diethylstilbestrol-exposed uterus and similar nonfusion anomalies: effects on subsequent reproductive performance; a preliminary report. AB - OBJECTIVE: To determine the feasibility of correcting the uterine abnormalities seen in diethylstilbestrol (DES)-exposed women and similar anomalies. DESIGN: Patients served as their own controls. SETTING: University based and private practice tertiary referral practice. PATIENTS: Eight patients referred for infertility, recurrent pregnancy loss, or both with an abnormal uterine contour as seen by hysterosalpingogram. INTERVENTION: Hysteroscopic metroplasty. OUTCOME MEASURES: Ability to conceive and carry pregnancy to livebirth. RESULTS: Three of five patients with secondary infertility and recurrent pregnancy losses had livebirths as did a patient with secondary infertility. Two patients with primary infertility failed to conceive. CONCLUSION: Metroplasty may decrease pregnancy loss in these patients but may not enhance fertility. PMID- 8458448 TI - Role of leuprolide acetate depot in hysteroscopic surgery: a controlled study. AB - OBJECTIVE: To evaluate leuprolide acetate (LA) depot (Enantone Depot, Takeda, Italy) when administered preoperatively in hysteroscopic surgery. DESIGN: Prospective, comparative study. SETTING: University Clinic of Obstetrics and Gynecology. PATIENTS: One hundred ninety-three patients (114 pretreated with LA depot and 79 controls) who underwent hysteroscopic surgery for uterine septa (group A), submucous fibroids (group B), and abnormal uterine bleeding (group C). RESULTS: In groups B and C there was a significant reduction in the operating time, bleeding during the operation, and the amount of distention medium required after LA depot administration, but no significant differences in surgical feasibility or efficacy were found in group A patients after treatment. CONCLUSION: Preoperative treatment with LA depot is effective in making hysteroscopic surgery easier. PMID- 8458449 TI - Gonadotropin-releasing hormone analogues for the treatment of endometriosis: long term follow-up. AB - OBJECTIVE: To determine the long-term recurrence rate of endometriosis after treatment with gonadotropin-releasing hormone analogues (GnRH-a). DESIGN: A historical prospective study. SETTING: Royal Free Hospital, London, a tertiary referral center for the treatment of endometriosis. PATIENTS: One hundred thirty patients with endometriosis had treatment with GnRH-a buserelin acetate, goserelin, and nafarelin acetate between the years 1985 and 1987. Patients no longer being followed in the gynecology clinic were sent a questionnaire to determine their state of health. Information was also requested from the patient's general practitioner. MAIN OUTCOME MEASURES: The cumulative recurrence rate for the fifth year after treatment ended was 53.4%. RESULTS: Patients with a higher disease stage at the outset were more likely to experience recurrence and experience it earlier than patients with minimal disease. Fifth-year recurrence rates were 36.9% for minimal disease and 74.4% for severe disease. The change in endometriosis stage classification scores at second-look laparoscopy for those patients whose disease recurred after treatment was not significantly different from those whose disease did not recur during the study period. CONCLUSIONS: Patients with endometriosis treated with GnRH-a are highly likely to suffer a recurrence of their disease, particularly if their disease is severe at the outset. PMID- 8458450 TI - Buserelin acetate in the treatment of pelvic pain associated with minimal and mild endometriosis: a controlled study. AB - OBJECTIVE: To evaluate the changes of pain symptoms induced by buserelin acetate, a gonadotropin-releasing hormone agonist, in a group of patients with endometriosis. DESIGN: Thirty-five infertile patients with one or more of the following symptoms (dysmenorrhea, pelvic pain, deep dyspareunia, and endometriosis stage I or II) were allocated randomly to treatment with buserelin acetate 1,200 micrograms/d IN for 6 months (n = 19) or expectant management (n = 16). Pain symptoms were recorded by the women themselves using a questionnaire that included two scales for pain evaluation: one analogue and one multidimensional. The treated and untreated patients were followed for a minimum of 18 and 12 months from the time of randomization, respectively. RESULTS: Buserelin acetate markedly reduced dysmenorrhea, pelvic pain, and dyspareunia during the treatment and also for the 12 subsequent months. During follow-up of the expectant management group, dysmenorrhea resolved in 19% (3/16) of the cases, and pelvic pain did not recur after diagnostic laparoscopy in one of the three women affected nor did deep dyspareunia in two of the five who reported the symptom before laparoscopy. CONCLUSION: Buserelin acetate induced a significant improvement of pain symptoms that persisted in approximately half of the patients even after withdrawal of the drug. However, symptoms associated with endometriosis showed a spontaneous remission in approximately one fifth of the untreated patients. PMID- 8458451 TI - A randomized comparative study of the metabolic effects of two regimens of gestrinone in the treatment of endometriosis. AB - OBJECTIVE: To study some of the metabolic effects of oral gestrinone on plasma lipoprotein risk markers for cardiovascular disease and on bone density, a risk marker for osteoporosis. DESIGN: Randomized double-blind study. SETTING: All patients were referred to Gynaecology Clinic of Royal Free Hospital Medical School. PATIENTS: Twenty premenopausal women with laparoscopically confirmed endometriosis. INTERVENTIONS: Subjects were randomized in a double-blind fashion to receive either 1.25 mg or 2.5 mg gestrinone two times per week for 6 months. MAIN OUTCOME MEASURE: Laparoscopy was performed before treatment, and clinical responses were determined by second laparoscopy after 6 months. Plasma lipid and bone density measurements during and after therapy were compared with baseline. RESULT: Median total endometriosis scores decreased from 7.5 to 1.0 in the 1.25 mg group and from 7.0 to 0 in the 2.5-mg group. There were no significant between group differences in endometriosis scores. At both doses, bone density in the spine and the proximal femur was conserved, but plasma concentrations of low density lipoproteins rose by 13% and those of high-density lipoproteins fell by 40%. CONCLUSIONS: Reducing the dose of gestrinone to 1.25 mg appeared to maintain the therapeutic effectiveness of this treatment but was still associated with potentially unfavorable effects on lipids and lipoproteins. PMID- 8458452 TI - Gonadotropin-releasing hormone agonist reduces the miscarriage rate for pregnancies achieved in women with polycystic ovarian syndrome. AB - OBJECTIVE: To compare the effect of treatment with gonadotropin-releasing hormone agonist (GnRH-a) and human menopausal gonadotropins (hMG) with that of gonadotropins only, on the cumulative livebirth rate and miscarriage rate of pregnancies achieved in women with polycystic ovarian syndrome (PCOS). DESIGN: Retrospective analysis of the outcome of 97 pregnancies according to the treatment protocol, with or without GnRH-a. Calculation of miscarriage rate and cumulative livebirth rate by life-table analysis. SETTING: Infertility clinic and in vitro fertilization (IVF) unit. PATIENTS: Women with polycystic ovaries (n = 239) who were clomiphene citrate failures and received either GnRH-a/hMG (n = 110) or gonadotropins only (n = 129) for ovulation induction (n = 138) or superovulation for IVF (n = 101). INTERVENTIONS: For ovulation induction, hMG was given in a step-up, individually adjusted dose scheme. For IVF, three ampules of pure follicle-stimulating hormone were given for 3 days followed by three ampules per day hMG and then individual dose adjustment. Gonadotropin-releasing hormone agonist (Decapeptyl, D-Trp6, microcapsules, 3.75 mg) was given in a single dose 2 weeks before gonadotropin treatment. MAIN OUTCOME MEASURES: The rate of early miscarriages (< 12 weeks) per pregnancies achieved was analyzed, and the cumulative livebirth rate for each treatment group was calculated by life-table analysis. RESULTS: Miscarriage rates after treatment in ovulation induction with (16.7%) and without GnRH-a (39.4%) and in IVF with (18.2%) and without GnRH-a (38.5%) were almost identical and were therefore analyzed together. Of pregnancies achieved with GnRH-a, 17.6% miscarried compared with 39.1% of those achieved with gonadotropins alone. Cumulative livebirth rate after four cycles for GnRH-a was 64% compared with 26% for gonadotropins only. CONCLUSIONS: Cotreatment with GnRH-a/hMG for anovulatory women with PCOS reduces the miscarriage rate and improves the livebirth rate compared with treatment with gonadotropins alone. PMID- 8458454 TI - The effect of clomiphene citrate treatment on cervical mucus and plasma estradiol and progesterone levels. AB - OBJECTIVES: To study the relationship between cervical mucus (CM) quality, postcoital test (PCT) results and plasma estradiol (E2) in clomiphene citrate (CC)-treated women. A subsidiary aim was to study the relationship between CM quality and plasma progesterone (P). DESIGN: Untreated women were compared with oligo-ovulatory patients given CC. SETTING: Infertility Clinic, Fazakerley Hospital, United Kingdom. PATIENTS, PARTICIPANTS: Fifty-one untreated patients and 31 women given CC. INTERVENTIONS: The treated women were given 50 mg/d CC from days 2 to 6 of their cycle. MAIN OUTCOME MEASURES: A CM assessment, a PCT, plasma E2, and P were performed at the anticipated time of ovulation based on at least two previous basal body temperature charts and menstrual patterns. RESULTS: In untreated women there was a very strong tendency for CM quality to improve with rising plasma E2 levels and to worsen with rising plasma P levels. There was a significant association between CM quality and PCT results. Similar results were found in CC-treated women, except that plasma E2 was very significantly higher and there was a significant inverse relationship between plasma E2 and CM quality. CONCLUSION: High plasma E2 in the periovulatory phase in CC-treated women is a marker for increased sensitivity to and continuing action of the antiestrogen. This impairs the quality of the CM. PMID- 8458453 TI - Hypothalamic-pituitary-ovarian response to clomiphene citrate in women with polycystic ovary syndrome. AB - OBJECTIVE: To examine the hypothalamic-pituitary sites of clomiphene citrate (CC) action in women with polycystic ovarian syndrome (PCOS). DESIGN: Prospective controlled trial. PATIENTS, PARTICIPANTS: Seventeen women with PCOS and 9 normal cycling women. INTERVENTIONS: Subjects with PCOS received CC, 150 mg/d for 5 days. MAIN OUTCOME MEASURES: Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels and LH pulse characteristics and their response to gonadotropin-releasing hormone (GnRH, 10 micrograms) were examined before and after 3 days of CC in PCOS subjects during a 12-hour frequent sampling study (n = 8). Daily urinary estrone glucuronide and pregnanediol glucuronide levels after CC were compared with concentrations in normal-cycling women through one menstrual cycle. In another nine PCOS subjects, pituitary and ovarian hormonal cyclicity was monitored by daily blood sampling. RESULTS: Thirteen of 17 treated cycles were ovulatory with normal luteal phases. In the ovulatory cycles, serum LH, FSH, estradiol (E2), and estrone levels increased after CC. Luteinizing hormone pulse frequency was unchanged, but LH pulse amplitude increased significantly after CC. Both LH and FSH response to exogenous GnRH was significantly attenuated after CC treatment. In anovulatory cycles, serum LH, FSH, and E2 increased initially and then returned to baseline and remained unchanged for the ensuring 40 days. CONCLUSIONS: Clomiphene citrate-induced ovulation in women with PCOS is accompanied by increased secretion of LH and FSH with enhanced estrogen secretion. The increased LH pulse amplitude after CC, together with decreased pituitary sensitivity to GnRH, suggests a hypothalamic effect. PMID- 8458455 TI - Association between ovarian changes assessed by transvaginal sonography and clinical and endocrine signs of the polycystic ovary syndrome. AB - OBJECTIVE: To determine whether ovarian polycystic changes estimated by transvaginal sonography correlate with clinical and endocrine findings associated with the polycystic ovarian syndrome. DESIGN: Prospective study. SETTING: Reproductive Endocrinology Unit in the Department of Obstetrics and Gynecology at a teaching hospital. PARTICIPANTS: Ninety-five consecutive patients suffering from oligoamenorrhea entering an infertility treatment program. INTERVENTIONS: All women were examined by transvaginal sonography, assessed for body mass index and hirsutism. Blood withdrawal was performed for hormone estimates. MAIN OUTCOME MEASURES: Ovarian follicle number, volume, and stroma echogenicity. Estimates of immunoreactive and bioactive luteinizing hormone (LH), testosterone (T), free T, insulin levels, and insulin resistance index were performed. RESULTS: Hirsutism was present in 63% of the patients and correlated with the number of follicles, ovarian volume, and stroma echogenicity. Follicle number, ovarian volume, and stroma echogenicity values were significantly correlated with immunoreactive LH, bioactive LH, and T levels. Both T and immunoreactive LH were independently correlated with ovarian structure sonography parameters. Insulin and insulin resistance correlated with ovarian volume and stroma echogenicity. Insulin resistance was of significant additional predictive value of ovarian volume and amount of stroma. Evaluating the predictive value of immunoreactive LH and T together in regard to all sonography parameters, only T levels were statistically significant predictors of increase in follicle number, ovarian volume, and stroma amount. CONCLUSIONS: Although immunoreactive LH and bioactive LH correlated with all ovarian parameters, the effect of androgens on ovarian changes appeared to be independent from LH. This further substantiates the apparent cardinal role of androgens in the genesis of polycystic ovaries. Besides, transvaginal sonography assessment of ovaries is a valuable additional tool for the diagnosis of PCOS. In this regard, insulin resistance is of additional predictive value for ovarian volume and stroma echogenicity. PMID- 8458456 TI - Computer-assisted observations of the normal menstrual cycle: predicting the day of ovulation. AB - OBJECTIVE: To develop a probabilistic computer model to predict the preovulatory days of the menstrual cycle by given hormonal parameters such as follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone (P). DESIGN: A computerized analysis program is specifically designed for the normal human menstrual cycle. The algorithm of this model incorporates the statistical aspects and the daily variations of FSH, LH, E2, and P. PATIENTS: This study includes 16 healthy fertile women with ovulatory cycles. INTERVENTIONS: Daily venous blood samples were collected from each subject from the first to the last day of the menstrual cycle. Radioimmunoassays were used to measure the four hormones in each blood sample. RESULTS: The computer implementation of this menu driven code that is flexible to accommodate differences in the hormone measurement procedures was accomplished. The distribution of measured hormone concentrations was validated to be normal. The best estimation of the ovulation day was highly dependent on the use of the band width (acceptable range) of the daily SD, which was +/- 1.45 in our laboratory. CONCLUSION: This computer model, heretofore named the CESME (Computer Enhanced Systems in Medicine and Engineering) developed by two of the authors, Ger and Karamete, with its reconfigurability enables the user to adopt the program to the normal values in their laboratory and use its clinically for predicting the probable periovulatory day(s) of the menstrual cycle. PMID- 8458457 TI - A prospective randomized trial of artificial insemination versus intercourse in cycles stimulated with human menopausal gonadotropin or clomiphene citrate. AB - OBJECTIVE: To determine the relative efficacy of intrauterine insemination (IUI), direct intraperitoneal insemination, and intercourse in cycles stimulated with clomiphene citrate (CC) or human menopausal gonadotropins (hMG). DESIGN: A prospective randomized trial with a 2(3) factorial design with eight different treatment alternatives. Only one cycle per couple was performed. SETTINGS: The Departments of Obstetrics and Gynecology, Central Hospital, Vasteras and Akademiska Hospital, Uppsala University, Uppsala, Sweden. PATIENTS: Of 157 randomized couples with unexplained infertility including 51 cases with minimal or mild endometriosis, 148 were selected for comparison. MAIN OUTCOME MEASURE: Pregnancy rate (PR). RESULTS: Follicular stimulation with hMG gave a higher PR than with CC in the insemination cycles, 19% (10/52) and 4% (2/49), respectively, but the PRs in intercourse cycles were not significantly different for hMG and CC, 13% (3/24) and 17% (4/23), respectively. Insemination cycles and intercourse cycles had a similar overall PR, 12% (12/101) and 13% (7/47), respectively. Furthermore, IUI and direct intraperitoneal insemination did not differ in efficacy. CONCLUSION: Follicular stimulation with hMG is more effective than CC in insemination cycles, but insemination as such seems to have no beneficial effect on the PR in stimulated cycles for treatment of unexplained infertility. PMID- 8458458 TI - Morphometric characteristics of endometrial biopsies after different types of ovarian stimulation for infertility treatment. AB - OBJECTIVE: To investigate whether various types of ovarian stimulation induce differences in endometrial development at the midluteal phase in infertile women. DESIGN: Assessment of stromal and glandular compartments in endometrial biopsies using morphometric criteria. SETTING: Institute for Hormone and Fertility Research, Hamburg, Germany. PATIENTS: The study included 18 women after treatment with human menopausal gonadotropin (hMG)/human chorionic gonadotropin (hCG) (group I), 23 women after clomiphene citrate (CC)/hMG/hCG treatment (group II), and 12 women after CC stimulation (group III). INTERVENTIONS: Endometrial biopsies and blood samples were taken simultaneously in the early to midluteal phase. To assess the time of ovulation, hormone analysis and regular checks by ultrasonography were performed. MAIN OUTCOME MEASURES: Morphometric evaluation of glandular and stromal structures revealed an impaired endometrial development after various treatment protocols. CONCLUSION: Ovarian stimulation in infertile women results in most cases in an elevation of steroid levels; however, the occurrence of an inadequate endometrial development might have an unfavorable influence on the outcome of implantation. Therefore, these findings may be of importance to the choice of treatment for infertility. PMID- 8458459 TI - The difference in miscarriage rates between menotropin-induced and natural cycle pregnancies is not surveillance related. AB - OBJECTIVE: To assess the reportedly higher miscarriage rate during menotropin induced cycle pregnancies as compared with natural cycle. DESIGN: Prospective cohort groups were selected, and pregnancies were identified 16 to 18 days after insemination and followed through to outcome. PATIENTS: Three hundred twelve patients were studied: 251 women receiving human menopausal gonadotropin and 61 requiring donor insemination without medication. RESULTS: A significant difference between the spontaneous abortion rate of gonadotropin-treated women (28.5%) and women conceiving during natural cycles (11.7%) was demonstrated. CONCLUSION: The opinion that higher miscarriage rates in menotropin-treated women are related to a surveillance bias compared with natural cycle conceptions should be reconsidered. PMID- 8458460 TI - Placental protein 14 levels in uterine flushing and plasma of women with unexplained infertility. AB - OBJECTIVES: To measure concentrations of placental protein 14 (PP14) in uterine flushings and plasma samples obtained from patients with unexplained infertility and to compare the results of those of normal fertile women. DESIGN: Prospective study. SETTING: Infertility and gynaecology outpatient clinics at the Jessop Hospital for Women, Sheffield, United Kingdom. PATIENTS: Sixteen patients with unexplained infertility and 12 normal fertile women who had been previously sterilized. INTERVENTIONS: Daily monitoring of luteinizing hormone (LH) to detect the LH surge; uterine flushings and blood samples were obtained on days 7, 10, and 12 after the LH surge. MAIN OUTCOME MEASURES: The measurement of PP14 concentration in uterine flushings and plasma samples throughout the luteal phase. RESULTS: Levels of PP14 in uterine flushings of patients with unexplained infertility were significantly lower than those of normal fertile women on days LH +10 and LH +12. No significant differences were observed between the two groups in PP14 levels in uterine flushings on day LH +7 and plasma samples on days LH +7, LH +10, and LH +12. CONCLUSIONS: Patients with unexplained infertility have reduced concentrations of PP14 in uterine flushings but not in plasma samples as compared with normal fertile women. Placental protein 14 measurement in uterine flushings may be a more valuable method of assessing endometrial function in infertile patients than plasma levels of the protein. PMID- 8458461 TI - Vulvar acanthosis nigricans: a marker for insulin resistance in hirsute women. AB - OBJECTIVE: To determine the frequency of acanthosis nigricans (AN) in a group of hirsute, hyperandrogenic women and to determine the body site most frequently affected. DESIGN: Cross-sectional observational study. SETTING: University teaching hospital. PATIENTS, PARTICIPANTS: Reproductive age, nonhypertensive, nondiabetic women referred for evaluation of hirsutism, documented to have hyperandrogenism, without medications known to influence lipid, carbohydrate, or hormonal metabolism. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Presence of AN. Insulin resistance was assessed by measuring fasting glucose, fasting insulin, and nadir glucose after a 0.1 U/kg i.v. insulin bolus in both obese and nonobese, hirsute, hyperandrogenic women. RESULTS: Twenty-four of 43 women were found to have AN. Although AN was identified at several body sites including the axilla (n = 14), on the nape of the neck (n = 13), below the breasts (n = 7), and on the inner thigh (n = 7), it was always present on the vulva in women who displayed one or more lesions. Acanthosis nigricans was found only in the obese, hirsute, hyperandrogenic women. These women were the most insulin resistant. CONCLUSIONS: Acanthosis nigricans and insulin resistance are found frequently in obese, hirsute, hyperandrogenic women. The vulva is the most likely place to find this marker. PMID- 8458462 TI - French National IVF Registry: analysis of 1986 to 1990 data. FIVNAT (French In Vitro National). AB - OBJECTIVE: To obtain a broad knowledge of IVF practice in France and to analyze the main success factors. DESIGN: Prospective study. SETTING: A national IVF registry was established in France in January 1986 and has been in operation since that time. PATIENTS: Data on more than 77,000 assisted reproductive technology (ART) cycles were collected from 97 centers, representing 80% of all French ART activity. INTERVENTIONS: In this registry, a form is completed for every oocyte recovery attempt, containing information about the infertility diagnosis, the attempt itself, and its results. MAIN OUTCOME MEASURE: The main outcome is the clinical pregnancy rate (PR) per ovum pick-up. RESULTS: This report provides data for the period 1986 to 1990 and studies the relationships between pregnancy occurrence and a number of characteristics relating to the couple or the cycle. The mean PR increased from 15.0% in 1986 to 18.7% in 1990. The methodological aspects are discussed, focusing on possible sources of bias and analysis of results. The results obtained in this registry are compared with those from other similar registries worldwide. PMID- 8458463 TI - Comparison of short 7-day and prolonged treatment with gonadotropin-releasing hormone agonist desensitization for controlled ovarian hyperstimulation. AB - OBJECTIVE: To compare two treatment regimens associating a gonadotropin-releasing hormone agonist (GnRH-a) and human menopausal gonadotropin (hMG) for controlled ovarian hyperstimulation (COH). DESIGN: A prospective randomized trial. SETTING: The outpatient fertility clinic of a university tertiary care center, the Hopital A. Beclere, Clamart, France. PARTICIPANTS: One hundred eighty-two in vitro fertilization (IVF) candidates undergoing new or repeat IVF cycles at Hopital A. Beclere over a 4-month period. TREATMENT: Group 1 (7-day protocol): A short acting preparation of GnRH-a (Tripteriline 0.1) was administered daily for 7 days, starting on cycle day 2. Ovarian stimulation with hMG was started on cycle day 4. Group 2 (long protocol): A timed release preparation of GnRH-a (Tripteriline 3.75 mg) was administered on cycle day 2. Ovarian stimulation with hMG was started after documented ovarian suppression. MAIN OUTCOME MEASURES: Response to COH, pregnancy rate (PR), tolerance. RESULTS: In the 7-day protocol, the amount of hMG required was markedly lower at 24 +/- 7 than in the long protocol group requiring 42.5 +/- 9.75 vials (75 IU) (mean +/- SD). No elevation of plasma LH occurred in either group. The number of oocytes retrieved was 7.3 +/ 1 and 10.7 +/- 1.2 (mean +/- SD) in the 7-day and long protocols, respectively. Yet, the number of embryos obtained and the PRs were similar in the two treatment groups. CONCLUSIONS: We observed that in COH, GnRH-a treatment could be interrupted safely several days before human chorionic gonadotropin administration without risking a premature increase of plasma luteinizing hormone. Moreover, the number of embryos available for fresh transfer and the ongoing PRs were similar in the new 7-day and in the classic long GnRH-a/hMG protocols, despite the smaller number of oocytes suggesting a greater efficiency of the 7-day protocol. The peak estradiol level and the hMG requirement were also lower in the 7-day GnRH-a/hMG protocol. PMID- 8458464 TI - Different morphology and proliferative ability of cumulus and granulosa cells originating from cystic follicles aspirated from stimulated in vitro fertilization patients. AB - OBJECTIVE: To investigate the morphology and proliferative ability of cumulus and granulosa cells (GCs) originating from cystic follicles and normal-sized follicles after ovarian stimulation. DESIGN: Granulosa cells, cumulus cells, and follicular fluid (FF) were aspirated from cystic follicles and normal-sized follicles from the same ovary. Morphology and proliferative ability of cumulus and GCs were assessed by Giemsa stain and thymidine incorporation, respectively. Cell proliferation was assessed in medium or FF originating from cystic follicles or normal-sized follicles. RESULTS: An oocyte was found in 40% of the cystic follicles versus 68% in the normal-sized follicles. Changes in dispersion and adhesion properties were observed in cystic versus normal aspirated corona cumuli complex. Proliferative ability was consistently lower in GCs originating from cystic follicles versus normal-sized follicles. Proliferation of GCs originating from normal-sized follicles or cystic follicles was inhibited or increased when grown in FF from cystic follicles or FF from normal-sized follicles, respectively. Differences in embryo quality were significantly in favor of oocytes originating from normal-sized follicles. Although the fertilization rate of those oocytes appeared to be higher, the difference was not of statistical significance. CONCLUSIONS: Inhibition of GC proliferation in FF from cystic follicles can be reversed by incubating cells in FF from normal-sized follicles. We conclude that factors in the FF may affect cell proliferation. PMID- 8458465 TI - Localization of antibodies on spermatozoa and sperm movement characteristics are good predictors of in vitro fertilization success in cases of male autoimmune infertility. AB - OBJECTIVE: To define sperm factors related to in vitro fertilization (IVF) failure in cases of antisperm autoimmunity. DESIGN: A detailed analysis of sperm morphology, movement characteristics, acrosomal function, and antibody binding was performed on the sperm population selected on a discontinuous two-layer Percoll gradient and used for IVF. The results were compared retrospectively between fertilizing (n = 13) and nonfertilizing (n = 11) sperm populations. PATIENTS: Twenty-one infertile couples undergoing 24 cycles of IVF treatment because of antisperm autoimmunity were included in this study. RESULTS: Fertilizing and nonfertilizing sperm populations were not different with respect to the percentage of motility, the normal morphology, the multiple anomalies index, the acrosome abnormalities, and the spontaneous or induced acrosome reaction. If the proportion of spermatozoa coated with either immunoglobulin (Ig)A or IgG antibodies was similar in the two groups, their localization was often different: antibodies were mainly on the sperm heads in the cases of fertilization failure. There were significant differences between fertilizing and nonfertilizing sperm samples in several movement parameters. Among them, the amplitude of lateral head displacement (ALH) was the most significantly correlated with fertilization success. Finally, spermatozoa were poorly bound to the zona pellucida (ZP) when fertilization failed, whereas high numbers of spermatozoa were attached to the ZP when fertilization occurred. CONCLUSION: Fertilization failure in patients with antisperm antibodies may be the result of several factors in which the impact of the antibodies on the membrane function play a critical role. Movement parameters, particularly the ALH and the localization of antibodies on migrated spermatozoa could predict the IVF failure or success more accurately than the proportion of antibody-coated spermatozoa in the inseminated populations. The fertilization failure was associated with an incapacity of spermatozoa to bind to ZP. PMID- 8458466 TI - Loss of fertility in men with varicocele. AB - OBJECTIVE: To test the hypothesis that men with varicocele who have already fathered children are immune to the detrimental effect of varicocele on their fertility and will continue to be fertile. If this were the case, one would expect a very low incidence of varicocele in currently infertile men who were able to father a child in the past (secondary infertility) compared with men who have never been fertile (primary infertility). DESIGN: Survey of men with male factor infertility. SETTING: Tertiary care university medical center. PATIENTS: One thousand ninety-nine infertile men of whom 98 (9%) met our criteria for secondary infertility. Men with prior vasectomy and men whose partners were over age 40 were excluded. MAIN OUTCOME MEASURE: Difference in the incidence of varicocele in men with secondary infertility versus primary infertility. RESULTS: A varicocele was palpable in 35% (352/1,001) of men with primary infertility and 81% (79/98) of men with secondary infertility. This difference in the incidence of varicocele was highly significant. Men with secondary infertility and varicocele were slightly older (37.9 versus 33.5 years), had a lower mean sperm concentration (30.2 versus 46.1 x 10(6)/mL), more abnormally shaped sperm (72% versus 40%), and higher mean serum follicle-stimulating hormone levels (17.6 versus 7.9 mIU/mL,) compared with men with primary infertility and varicocele. CONCLUSIONS: The incidence of varicocele is much higher in male factor secondary infertility compared with primary infertility. These findings suggest that varicocele causes a progressive decline in fertility and that prior fertility in men with varicocele does not predict resistance to varicocele induced impairment of spermatogenesis. Men with a varicocele may benefit from early evaluation and prophylactic varicocelectomy to prevent future infertility. PMID- 8458467 TI - The pH as an important determinant of sperm-mucus interaction. AB - OBJECTIVE: To determine the clinical significance of endocervical mucus pH on sperm-mucus interaction during infertility investigation. PATIENTS AND MATERIAL: Two hundred sixteen couples with a median duration of infertility of 4 years (range, 1 to 19 years) presenting at the infertility unit of the Women's University Hospital of Heidelberg, Germany. MAIN OUTCOME MEASURES: Determination of endocervical pH by colorimetric and electrometric measurement and correlation of results with the outcome of postcoital testing (PCT) and other parameters of infertility investigation (semen and cervical mucus [CM] quality, microbial colonization of cervix and ejaculates, medical history, hormonal status, and specific medication) and the subsequent fertility in a prospective study. In vitro experiments with the sperm-cervical mucus penetration test (SCMPT) used as biological model. RESULTS: The colorimetric determination of endocervical mucus pH is an easy method, suitable for routine clinical use, correlating significantly with electrometric measurement of pH. Median pH was 7.0 (range, 5.4 to 8.2). The mucus pH was significantly related with the results of PCT, even when mucus and semen variables were taken into account. No significant relationship was seen between the cervical index and mucus pH and the microbial colonization of cervix and ejaculates. The pH of endocervical secretions correlated with the peripheral hormonal status: low pH levels were significantly more frequent in patients with hyperandrogenemia, indicated by high testosterone and/or dehydroepiandrosterone sulfate levels before medication was started, and in hyperandrogenemic patients treated with dexamethasone than in the other women. Oral administration of estrogens led to a subtle alkalinization of the CM. With regard to subsequent fertility 6 months after pH testing, the pregnancy rate was significantly lower in women offering reduced mucus pH on occasion of the PCT in the group of couples with primary infertility and in couples with oligozoospermia of the male partner. The significant influence of pH on sperm-mucus interaction was confirmed in vitro with the SCMPT. CONCLUSIONS: The results indicate that the pH of the CM, easily determined with pH indicator paper, is an important parameter of mucus quality with significant influence on spermatozoal viability in CM, which correlates with peripheral hormonal status and can be affected by oral medication with estrogens. Therefore the routine determination of pH on occasion of the PCT is recommended during infertility investigation. PMID- 8458468 TI - A novel view of albumin-supported sperm capacitation: role of lipid transfer protein-I. AB - OBJECTIVE: To determine if one mechanism of albumin-mediated support of human sperm capacitation is lipid (cholesterol) transfer activity and contamination of albumin with Lipid Transfer Protein-I (LTP-I). DESIGN AND MAIN OUTCOME MEASURES: Measure lipid transfer activity in various bovine and human albumin preparations, relate this activity to albumin-supported capacitation (measured by zona-free hamster oocyte sperm penetration assay) and acrosome reactions; and attempt to detect LTP-I in active albumins. Remove LTP-I from albumin which supports capacitation and reassess this support. Reconstitute capacitation support by addition of purified LTP-I. SETTING AND SUBJECTS: Healthy sperm donors with normal semen analyses were recruited by the Reproductive Biology-Andrology Laboratory in a university medical center. RESULTS: Albumin preparations that effectively support capacitation have high levels of lipid transfer activity and of LTP-I, a protein responsible for lipid transfer activity. Preparations with lower levels of capacitation support have less lipid transfer activity. Removal of LTP-I from supportive albumin significantly reduces the capacitation support, and this is restored by purified LTP-I. Progesterone concentrations in these preparations are negligible. CONCLUSIONS: The variable abilities of albumin preparations to support in vitro sperm capacitation are largely dependent on the presence of contaminating LTP-I. The cholesterol transfer activity of this protein, which is present in human serum and follicular fluid, may be one mechanism in the process of capacitation. PMID- 8458469 TI - Detection of antisperm antibodies on the surface of living spermatozoa using flow cytometry: preliminary study. AB - OBJECTIVE: To assess the use of flow cytometry (FCM) analysis of living spermatozoa subjected to indirect immunofluorescence staining with the mouse anti human immunoglobulin (Ig)G monoclonal antibodies (FCM test) as an objective method for the detection of antisperm antibodies in semen and serum. DESIGN: The comparative studies were conducted with the direct and indirect mixed antiglobulin reaction (MAR) and FCM test performed by FCM analyzer FACSCAN (Becton Dickinson Immunocytometry Systems, Mountain View, CA). SETTING: Clinical infertile service. PATIENTS: Seventy-six semen and 20 sera samples of infertile patients were analyzed. RESULTS: For IgG in semen there was a highly significant correlation between the direct MAR and FCM test. Six of 12 IgG-positive samples revealed also IgA, and just one sample, which showed negative MAR, was positive for IgM in FCM test. Flow cytometry test and indirect MAR showed also a highly significant correlation of the results of IgG detection in sera. CONCLUSIONS: Flow cytometry test may be used to verify that IgG antisperm antibodies are on the surface of living spermatozoa either retrieved directly from an ejaculate or after exposure to serum and to determine proportion of antisperm antibodies positive spermatozoa, titer, and quantity of antibodies bound to the cell surface. PMID- 8458470 TI - First pregnancies and livebirths from transfer of sodium alginate encapsulated embryos in a rodent model. AB - OBJECTIVE: To determine the effect of sodium alginate encapsulation of rodent embryos on in vitro embryonic cleavage rates, implantation rates, and livebirth rates, and to find the in vivo degradation time for the capsules. DESIGN: Studies were conducted using both CB6F1 mice and Golden Syrian hamsters. RESULTS: Capsules made with 3.0% sodium alginate degraded in vivo within 24 to 48 hours after transfer. In vitro embryonic cleavage of encapsulated embryos was not impaired, nor were implantation rates in CB6F1 mice. Finally, 8.6% of transferred encapsulated embryos resulted in livebirths. CONCLUSIONS: Encapsulation of rodent embryos in 3.0% sodium alginate is not detrimental to embryonic development, implantation rates, or fetal development. Because the capsule degrades within 48 hours after transfer, encapsulating embryos may be beneficial for human in vitro fertilization and embryo transfer. PMID- 8458471 TI - The ascites in the ovarian hyperstimulation syndrome does not originate from the ovary. AB - OBJECTIVE: To evaluate the direct ovarian contribution to ascites formation in the ovarian hyperstimulation syndrome (OHSS) in a rabbit model. DESIGN: Prospective experimental study. SETTING: Research center of a university teaching hospital. PARTICIPANTS: New Zealand White rabbits. INTERVENTIONS: Both ovaries of the rabbits in the experimental group were enclosed within a pouch developed from the surrounding peritoneum and mesosalpinx by microsurgery. Animals in the control group did not undergo any surgical intervention. Ovarian hyperstimulation was induced by alternate day equine chorionic gonadotropin and intermittent human chorionic gonadotropin (hCG). MAIN OUTCOME MEASURES: Degree of ascites formation and the morphological and endocrinologic signs of ovarian hyperstimulation. RESULTS: The serial plasma estradiol and progesterone levels, ovarian weights, and ascites response were not statistically different between the two groups. CONCLUSIONS: Isolation of both ovaries from the peritoneal cavity does not prevent ascites formation in the OHSS. Increased transudation across extraovarian serosal surfaces contributes to ascites formation in OHSS. PMID- 8458472 TI - Successful twin pregnancy and delivery after microinseminated oocyte fallopian transfer for male factor infertility. AB - The case described indicate that microinseminated oocyte fallopian transfer may be a potentially useful option of management of male factor infertility. The question of the effect of a breach in the oocyte/embryo zona during micromanipulation procedure on the outcome of their in vitro culture remains to be addressed. PMID- 8458473 TI - Basal follicle-stimulating hormone level and age affect the chance for and outcome of pre-embryo cryopreservation. AB - All IVF cycles in which subsequent transfers of thawed pre-embryos occurred were studied. Both age and basal (cycle day 3) FSH level are important determinants of the chance for cryopreservation and the performance of cryopreserved pre-embryos. Although there was no age or FSH level above which pregnancy with frozen pre embryos was not possible, the chances clearly decline. Thus, consideration to transferring larger numbers of pre-embryos fresh should be given to women in the fifth decade and those with basal FSH > 15 IU/L. PMID- 8458474 TI - Serum progesterone and estradiol concentrations in the early diagnosis of ectopic pregnancy after in vitro fertilization-embryo transfer. AB - To determine if discriminatory P or E2 concentrations can be established for early diagnosis of EP after IVF, 282 pregnancies were studied 11, 13, 15, and 17 days after ET. Receiver-operator characteristic analysis of P and E2 indicated no clinically useful threshold value for EP. No significant differences in P or E2 was seen when intrauterine and extrauterine pregnancies or viable and nonviable pregnancies were compared. All EPs had P < 50 ng/mL and E2 < 500 pg/mL at 11 days after ET. Serum P and E2 cannot differentiate EPs from intrauterine pregnancies nor viable from nonviable pregnancies resulting from IVF. PMID- 8458475 TI - The safety of physiological estrogen plus progestin replacement therapy and with oral contraceptive therapy in women with pathological hyperprolactinemia. AB - In summary, E- replacement therapy may be administered to women with E deficiency, despite the presence of pathological hyperprolactinemia, with apparently no adverse effect on the underlying disease process. The concern of induction of rapid growth of an underlying pituitary adenoma was not substantiated. PMID- 8458476 TI - Leuprolide acetate and bone mineral density measured by quantitative digitized radiography. AB - Quantitative digitized radiography uses low-energy photons to measure bone density with precision not available in older techniques. Using this method, lumbar spine density was evaluated in 12 women before and after 6 months of therapy with LA. A 2.9% decrement in mean bone density was documented. The reproducibility of quantitative digitized radiography suggests that this small degree of bone mineral loss is a real phenomenon and not an artifact of measurement. The clinical significance of this degree of bone mineral loss has yet to be established. PMID- 8458477 TI - Acute urinary retention after gonadotropin-releasing hormone agonist treatment for leiomyomata uteri. AB - A case of rapid uterine enlargement and subsequent urinary retention occurring 7 days after GnRH-a administration in a 53-year-old premenopausal woman with myomas is presented. Rapid uterine enlargement was presumed to be caused by hyperestrogenism shortly after GnRH-a administration. The patient was treated with an indwelling Foley catheter for 2 weeks until the uterus decreased to near baseline dimensions. The patient's uterus continued to decrease in size during the 12 weeks she received GnRH-a, and she underwent an uneventful total abdominal hysterectomy and bilateral salpingectomy/oophorectomy after donating 2 units of autologous blood. This case illustrates that adverse effects from GnRH-a treatment may be caused by the transient increase in ovarian steroid secretion shortly after drug administration. PMID- 8458478 TI - Ruptured pelvic abscess after intrauterine insemination: a case report. AB - This case reports a serious but previously unreported complication of IUI. Further reports of serious infection would warrant consideration of antibiotic prophylaxis in some cases. PMID- 8458479 TI - Morphometric study of the stromal vascularization in peritoneal endometriosis. AB - To evaluate the stromal vascularization of different appearances of peritoneal endometriosis, biopsies were taken from peritoneal areas with endometriosis in a series of 135 infertile women and classified as typical (black), red, or white lesions. The number of capillaries per mm2 of stroma, their mean surface area, and the ratio of capillaries/stroma surface area, and the mitotic activity were analyzed in typical, red, and white lesions. Significant differences were found between the different subgroups. The higher vascularization and mitotic activity observed in red lesions suggested the hypothesis that such lesions are very active and probably the first stage of early implantation of endometrial glands and stroma. The poor vascularization and the absence of mitosis observed in white lesions suggested that these lesions are much less active than red lesions and are a quiescent stage of the disease. Our study proves that the "activity" of peritoneal endometriosis is related to the vascularity. This concept must be considered in the further discussion of American Fertility Society Endometriosis Classification. Typical, red and white lesions are three different stages of the peritoneal disease and their relative relation to infertility is also probably different. PMID- 8458480 TI - Psychosocial stress as a cause of infertility. AB - An adaptive model for the evolution of reproductive failure predicted psychosocial stress to increase as anatomic causes of infertility decrease. The nonanatomic infertility group in our study reported greater psychosocial stress than intermediate (P < 0.008) or anatomic groups (P < 0.0005). Controls, women with nonanatomic etiologies who were not attempting pregnancy, also reported higher psychosocial stress than the anatomic group (P < 0.007). Results are consistent with the hypothesis that psychosocial distress contributes significantly to the etiology of some forms of infertility. PMID- 8458481 TI - Selection of single-stranded deoxyribonucleic acid spermatozoa via the SpermPrep filtration column. AB - Eighteen semen samples were collected from 18 normospermic men. Two aliquots (1 mL) were prepared from each ejaculate, washed with Ham's F-10, and each washed sperm pellet was reconstituted in 2 mL volume of Ham's F-10 medium. Each aliquot one was stained using the AO-staining method. Each aliquot two was filtered via the SpermPrep II method, and the recovered spermatozoa were stained similarly. The proportion of single-stranded DNA (red) spermatozoa to double-stranded (green) spermatozoa was significantly higher in aliquot one than in the postfiltered sample (aliquot two), suggesting that the SpermPrep filtration procedure selectively entrapped the spermatozoa with abnormal DNA. PMID- 8458482 TI - Pubertal varicocele: correlation between clinical, Doppler, and hormonal findings. AB - Clinical, Doppler, and hormonal findings in puberal patients with unilateral and bilateral varicocele were evaluated. No correlation was found between clinical and hormonal findings. A significant increase was found in LH response to LH-RH in patients with bilateral varicocele as well as an increase in T to hCG in those with unilateral varicocele with prolonged reflux. Further longitudinal, hormonal, and Doppler studies in puberal patients might provide information about the most useful parameters to define those individuals at higher risk of having future problems. PMID- 8458483 TI - Proteins of movement. PMID- 8458484 TI - Tests of sperm function. PMID- 8458485 TI - Osteoporosis: screening, prevention, and management. AB - OBJECTIVE: To present clinical recommendations for osteoporosis prevention that include new support for routine bone mass screening of asymptomatic perimenopausal high-risk women. Technological advances make it conceivable that osteoporosis, a metabolic bone disorder rather than a true disease, can be prevented on a wide scale and eventually eliminated. Effective prevention requires that advanced screening procedures be easily accessible and reimbursable as a wise healthcare investment. STUDY SELECTION: This article reviews research bearing on clinical management of women potentially at risk for osteopenia and osteoporosis. Background includes the pathogenesis of osteoporosis and known risk factors such as heredity, life-style, gynecological history, eating disorders, endocrinopathies, and scoliosis. Studies of bone mass measurement favor dual energy roentgenographic absorptiometry as the bone densitometry method of choice for screening women at risk and for use with roentgenograms in evaluating bone health. The balance between bone formation and resorption can be assessed by a number of biochemical markers, which are reviewed. Other factors known to affect bone mass are discussed. CONCLUSIONS: Primary care physicians, especially gynecologists, can play a pivotal role by [1] identifying women with higher risks for osteoporosis at earlier ages; [2] stressing the importance of developing maximal bone mass before menopause; and [3] developing individualized patient prescriptions for bone mass determinants under personal control: exercise, nutrition (e.g., calcium and vitamin D), life-style, and hormone replacement therapy. PMID- 8458486 TI - Controversies in the development and validation of new sperm assays. PMID- 8458487 TI - Age and follicular phase estradiol are better predictors of pregnancy outcome than luteinizing hormone in menotropin ovulation induction for anovulatory polycystic ovarian syndrome. AB - OBJECTIVE: To examine the relationship of baseline and preovulatory serum E2, P, and LH levels and age with pregnancy outcome in polycystic ovarian syndrome (PCOS) patients undergoing hMG ovulation induction. DESIGN: Retrospective analysis of all available data over 2 years. SETTING: Tertiary referral ovulation induction clinic. SUBJECTS: Forty-four anovulatory PCOS patients with 25 ovulatory nonconception and 50 conception cycles after hMG ovulation induction. MAIN OUTCOME MEASURES: Ovulation (midluteal serum P > 25 nmol/L [7.86 ng/mL]); pregnancy (serum beta-hCG > 30 mIU/mL 16 days after ovulating injection); pregnancy outcome: pregnancy termination < 20 weeks' or > or = 20 weeks' amenorrhea. RESULTS: Of the endocrine parameters considered, none was significantly different in nonconceptive and conceptive ovulatory cycles. Miscarriage was associated with low basal serum E2: median value for pregnancies ending < 20 weeks, 105 pmol/L (28.6 pg/mL) and for > or = 20 weeks 150 pmol/L (40.9 pg/mL). It was also significantly associated with age. For patients > 29.5 years of age, (29.5 years, population mean age) a baseline E2 < or = 140 pmol/L (38.2 pg/mL) had sensitivity 92%, specificity 54%, positive predictive value 65%, and negative predictive value 87% for the prediction of miscarriage. The nature of the previous cycle, the day of the cycle on which therapy commenced, and a past history of miscarriage were not related either to pregnancy outcome or to basal serum E2. PMID- 8458488 TI - Long-term naltrexone treatment normalizes the pituitary response to gonadotropin releasing hormone in polycystic ovarian syndrome. AB - OBJECTIVE: To investigate the influence of opioid system on the exaggerated LH response to GnRH test in the polycystic ovarian syndrome (PCOS). DESIGN: Pituitary stimulation (GnRH 100 micrograms) in a group of PCOS patients under basal condition and after 4 weeks of treatment with naltrexone. RESULTS: In the PCOS group, the naltrexone treatment determines a significant reduction of the LH response (calculated as the area under curve) to GnRH test, with a similar significant decrease of the LH:FSH. CONCLUSION: Naltrexone normalizes in the PCOS group the pituitary response to GnRH test, abolishing every statistical differences with the control group. PMID- 8458489 TI - Induction of follicular growth using recombinant human follicle-stimulating hormone in two volunteer women with hypogonadotropic hypogonadism. AB - OBJECTIVE: To examine the safety, tolerance, pharmacokinetics, follicular growth, and steroidogenesis after the administration of recombinant human FSH (Org 32489; Organon International, Oss, The Netherlands) in women with isolated hypogonadotropic hypogonadism. DESIGN: An open phase I multiple rising dose study with recombinant FSH in two hypogonadotropic but otherwise healthy women. The drug was administered intramuscularly one time per day for a maximum of 21 days, i.e., 75 IU for the first 7 days, 150 IU for the next 7 days, and 225 IU during the last 7 days. Treatment was discontinued if serum E2 was > or = 1,100 pmol/L and/or one or more growing follicle > 14 mm in diameter was observed. After the last recombinant FSH injection, subjects were monitored for another 3 weeks. SETTING: Specialist Reproductive Endocrinology and Infertility Unit. VOLUNTEERS: Two women with isolated hypogonadotropic hypogonadism who did not want to get pregnant anymore. MAIN OUTCOME MEASURES: Serum FSH, androstenedione (A), T, P, LH, follicular growth, and endometrial thickness. Safety parameters: blood pressure, heart rate, urinalysis, hematology, blood biochemistry, and antirecombinant FSH antibodies. RESULTS: Treatment with recombinant FSH resulted in dose-related increases of serum FSH. Both women showed follicular growth (diameter, 17 mm), whereas serum A concentrations were very low, and serum E2 concentrations rose to only 76.7 and 139.5 pmol/L, respectively. No antirecombinant FSH antibody formation or changes of safety variables were noted. CONCLUSION: This study in two women with hypogonadotropic hypogonadism is consistent with the two-cell theory that FSH alone can induce follicular growth. The low concentrations of A and E2 indicate the need for LH to induce appropriate steroidogenesis. It was also found that recombinant FSH is well absorbed, safe, and well tolerated after daily treatment for up to 21 days. PMID- 8458490 TI - Assessment of ovarian and uterine blood flow by transvaginal color Doppler in ovarian-stimulated women: correlation with the number of follicles and steroid hormone levels. AB - OBJECTIVE: To study the changes that occur in vascular resistance to flow in the utero-ovarian circulation and their correlation with the number of follicles and steroid hormone levels in patients undergoing ovarian stimulation with gonadotropin. DESIGN: In a prospective study, the impedance to flow in the intraovarian and uterine vessels was measured by means of transvaginal color flow Doppler imaging throughout the cycle. SETTING: University-based IVF program. PATIENTS: Eleven infertile patients undergoing ovarian stimulation with gonadotropin in preparation for IVF and ET. MAIN OUTCOME MEASURES: Intraovarian, uterine, and arcuate artery blood flow velocity waveforms, follicular growth, and serum E2 and P concentrations throughout the cycle. RESULTS: Pulsatility index (PI) of the intraovarian blood vessels and uterine artery decreased gradually during the follicular and luteal phase. The PI of the arcuate artery did not change significantly. The PI of the intraovarian blood vessels correlated with the number of follicles (> 15 mm; day of hCG). Serum E2 concentrations but not P demonstrated negative linear correlation with the PI of the intraovarian vessels and uterine artery. CONCLUSIONS: Induced cycles are associated with decreased impedance to blood flow in the utero-ovarian circulation. Intraovarian PI correlates negatively at each stage of the cycle with the eventual number of preovulatory follicles. Little or no changes are observed when the response to ovarian stimulation is poor. PMID- 8458491 TI - Premature ovarian failure--the prognostic application of autoimmunity on conception after ovulation induction. AB - OBJECTIVE: To assess whether the presence of autoimmune activity in patients with premature ovarian failure (POF) can predict the response to ovulation induction and conception. DESIGN: Assessment of autoimmune activity in patients with POF, correlating the response to ovulation induction with this autoreactivity. SETTING: Tertiary care academic center. PATIENTS: Forty women with POF, 15 of them treated by ovulation induction because of infertility. INTERVENTIONS: All patients were tested for the presence of autoimmune activity, antibodies against various tissues, and 15 of them were treated with combinations of hMG/hCG, glucocorticosteroids as immunosuppressant, and some of them also with a long acting GnRH agonist. Those patients not interested in infertility were put on hormone replacement therapy (HRT). MAIN OUTCOME MEASURES: Serum E2 and P were measured during ovulation induction as well as follicular diameter monitoring by transvaginal sonography. Achievement of gestations and their outcome were monitored in the group in which ovulation induction was accomplished. RESULTS: Antibodies against thyroglobulin, nuclear antigens, heart, tissue gluten, or increased levels of immunoglobulin (Ig)M, or decreased levels of complement C3 and C4 were significantly different in the patients with POF than in the control population. Autoreactivity of at least one class of the tested antibodies was found in 31 of 40 patients (77%). In 15 patients with autoimmune activity who have undergone ovulation induction using hMG/hCG, 14 pregnancies were achieved in 8 patients. Two of the pregnancies were spontaneous, and 12 were generated by hMG/hCG and fluocortolone, with or without pretreatment with GnRH-a. Twelve healthy babies were generated by 10 gestations, 3 ended in spontaneous abortions (23%), and 1 is ongoing. All the nonspontaneous pregnancies were achieved in the first three cycles of ovulation induction. CONCLUSIONS: Patients with POF and autoimmune activity, suggesting an autoimmune etiology to the ovarian failure, may respond to ovulation induction and have a conception rate of approximately 40% in three cycles. Those who do not conceive in three treatment cycles have a very low probability to conceive; therefore, further attempts of ovulation induction should be discouraged. However, some patients may spontaneously conceive in association with HRT. PMID- 8458492 TI - Relationship of endometrial thickness and pattern to fecundity in ovulation induction cycles: effect of clomiphene citrate alone and with human menopausal gonadotropin. AB - OBJECTIVE: To determine if preovulation endometrial thickness or pattern are related to fecundity and to use of clomiphene citrate (CC) or hMG in IUI. DESIGN: Prospective ultrasound evaluation the day of hCG after CC alone (n = 197), hMG alone (n = 49), concurrent hMG or sequential CC and hMG (n = 205), and no medications (n = 23). SETTING: Private fertility clinic. PATIENTS: Two hundred seventy-one patients undergoing 474 cycles of IUI. MAIN OUTCOME MEASURES: Endometrial thickness, pattern, per cycle fecundity, and continuing pregnancy. RESULTS: Endometrial thickness was related to fecundity and continuing pregnancy. No pregnancies occurred when thickness was < 6 mm. The continuing pregnancy rate was 12.6% when thickness was > or = 9 mm, compared with 6.9% when thickness was 6 mm to 8 mm. Endometrial pattern was unrelated to pregnancy. Average endometrial thickness was decreased when hMG and CC were used in combination (7.9 mm) compared with hMG alone (9.4 mm). Endometrial thickness was negatively related to CC dose and positively related to the day of hCG administration by ANOVA. CONCLUSIONS: Endometrial thickness the day of hCG administration is prognostic of fecundity and continuing pregnancy in cycles of ovulation induction. PMID- 8458493 TI - Pulsatile luteinizing hormone secretion pattern in hyperandrogenemic women. AB - OBJECTIVE: To elucidate changes in gonadotropin secretion pattern in patients with hyperandrogenemic chronic anovulation of various origins. DESIGN AND PARTICIPANTS: Hyperandrogenemic patients (n = 32), divided into subgroups according to certain clinical and biochemical criteria, and a control group (n = 9) of regularly cycling women with normal androgen and PRL levels were prospectively investigated. SETTING: Infertility and Biochemical Endocrinology Unit, Department of Obstetrics and Gynecology, University of Dusseldorf, Dusseldorf, Germany. MAIN OUTCOME MEASURES: Blood samples for radioimmunological analyses of gonadotropins and steroids were taken at 10-minute intervals for 12 hour sampling periods. In nonamenorrheic patients, investigations were performed on the 5th day of a cycle. Pulsatile LH and FSH data were analyzed by computerized peak identification programs. RESULTS: In hyperandrogenemic women, mean LH levels were higher than controls, the most elevated concentrations being observed in women with secondary amenorrhea (subgroup 5), in those selected for elevated mean LH levels (subgroup 3), and in those with elevated T and/or androstenedione (A) but normal DHEAS levels (subgroup 1). With the exception of patients with DHEAS elevations but normal T and A levels (subgroup 2), LH pulse frequency and amplitude were increased with most distinct effects occurring in subgroups 3 and 5. Highly elevated T and free T levels were observed in subgroup 5 and in overweight patients (subgroup 6). Estrone (E1) serum concentrations were highest in those subgroups (3 and 5) in which acceleration of LH pulse frequency and increments in LH pulse amplitude were most pronounced; these parameters correlated significantly with E1 levels. CONCLUSIONS: Changes in pulsatile LH release in patients with hyperandrogenemic chronic anovulation correlate primarily with elevated E1 levels, rather than with T or A serum concentrations. PMID- 8458494 TI - Reproductive prognosis after hysteroscopic metroplasty in 102 women: life-table analysis. AB - OBJECTIVE: To evaluate reproductive prognosis after hysteroscopic metroplasty. DESIGN: The cumulative proportions of women who became pregnant and gave birth, subdivided according to previous obstetric history, were calculated by the product limit method and compared using the log rank test. SETTING: Outpatient infertility clinic of Milan University. PATIENTS: One hundred two consecutive patients with complete (n = 23) or partial septate uterus (n = 79) referred because of infertility or repeated abortion. INTERVENTION: Hysteroscopic metroplasty performed by microscissors (n = 80), argon laser (n = 10), or electroresectoscope (n = 12). MAIN OUTCOME MEASURES: Postoperative cumulative pregnancy and birth rates. RESULTS: At 36 months the cumulative pregnancy and birth rates were 89% and 75%, respectively, in the septate uterus group and 80% and 67% in the subseptate uterus group. CONCLUSIONS: Reproductive prognosis after hysteroscopic metroplasty was favorable and not influenced by the malformation subclass. PMID- 8458495 TI - Methotrexate treatment of ectopic pregnancy: 100 cases treated by primary transvaginal injection under sonographic control. AB - OBJECTIVE: To evaluate safety and efficacy of intrasaccular methotrexate (MTX) for treatment of ectopic pregnancy (EP). DESIGN: Longitudinal nonrandomized trial of MTX treatment of EP. SETTING: Department of Obstetrics and Gynecology (A. Beclere Public Hospital, Clamart, France Paris-Sud University). PATIENTS: One hundred patients with an EP visualized by sonography. Patients were 31.4 +/- 4.8 years old, para 0 to 4, and gravida 0 to 7. Twelve patients had a past history of EP, and 18 had previously undergone tubal surgery. Inclusion score for proposed medical treatment used six criteria graded from 1 to 3: gestational age, initial hCG level, P level, existence of abdominal pain, size of hemoperitoneum, and diameter of hematosalpinx. Eleven patients had an EP with cardiac activity. Treatment consisted of MTX, 1 mg/kg, given locally under transvaginal sonographic control. RESULTS: Eighty-three of 100 patients were considered to be completely cured (return of hCG to < 10 mIU/mL). The success rate was 92.8% with an initial hCG level < 5,000 mIU/mL and 87% when the score was < or = 12. Seven of the 11 patients with an EP with cardiac activity were treated successfully, including 5 of 7 when the initial score was < or = 12, and all failures concerned cases with an initial score > 12. Twenty-eight of 83 patients treated successfully required more than one injection of MTX (additional doses being given intramuscularly) because of nonresolution of hCG levels. Follow-up hysterosalpingography was performed in 80 patients showing 90% tubal patency on the side of the treated EP. Of 58 patients wishing pregnancy, 34 pregnancies occurred, including 25 ongoing or delivered. We observed a low recurrence rate of EP (3 with 1 on the same side). CONCLUSION: Treatment by initial transvaginal injection of MTX under sonographic control appears to be simple and effective, with no demonstrable untoward effects. The tubal patency and subsequent fertility obtained appear satisfactory. The highest success rate is observed when hCG level is under 5,000 mIU/mL and/or a pretherapeutic score < or = 12 when EP is visualized by sonography. PMID- 8458496 TI - Angiogenic activity of peritoneal fluid from women with endometriosis. AB - OBJECTIVE: To investigate the presence of angiogenic factors in peritoneal fluid (PF) and follicular fluid (FF). DESIGN: The PF samples of 48 women with (n = 24) or without (n = 24) endometriosis were investigated. Angiogenesis was assayed using the chorioallantoic membrane of 11-day-old fertilized chicken embryos. Glass fiber prefilters impregnated with the fluids were placed on the chorioallantoic membrane. MAIN OUTCOME MEASURE: The vascular reaction was analyzed by an independent observer after 72 hours. RESULTS: There was a positive reaction in 58.3% of the PF from women with endometriosis and in 12.5% of the women without endometriosis. No correlation was found between the angiogenic response and the severity of endometriosis. The reaction remained after charcoal treatment of the PF. Positive reaction was found in three of six FF samples. CONCLUSION: The PF of women with endometriosis contain more angiogenic factors than PF from women without endometriosis. This angiogenic activity could be important for the further outgrowth and progression of the lesions. PMID- 8458497 TI - Isolation and long-term culture of human preantral follicles. AB - OBJECTIVE: To isolate intact preantral follicles from the human ovary for in vitro studies. PROCEDURE: Premenopausal human ovary was digested by a mixture of collagenase and deoxyribonuclease (DNase) for 1 hour at 37 degrees C and for 36 hour at 4 degrees C. Intact preantral follicles at classes 1 and 2 were isolated and cultured for up to 120 hours in a serum-free Dulbecco's modified Eagle's medium (GIBCO, Grand Island, NY) with ITS+ (insulin, transferrin, selenium, linoleic acid, and bovine serum albumin; Collaborative Research, Bedford, MA) with or without FSH. Follicular DNA synthesis was measured by [3H]thymidine incorporation, whereas steroidogenic capacity was assessed by P, androstenedione (A), and 17 beta-E2 RIA. The morphology of long-term cultured follicles was studied by routine histologic procedure. RESULTS: A large number of intact, preantral follicles was efficiently dissociated from a portion of ovary. Morphologically, follicles were healthy and did not have any thecal layer. Follicle-stimulating hormone, in vitro, induced follicular DNA synthesis by 24 hours and antrum formation in class 2 follicles after 120 hours. Both class 1 and 2 follicles were able to produce a small basal amount of P and A, but they did not produce any measurable E2. However, both classes synthesized increasing amounts of P, A, and E2 after FSH exposure. CONCLUSION: This is a first report of a successful enzymatic isolation of human preantral follicles and their long-term culture in vitro. The growth and differentiation of preantral follicles by FSH clearly indicate the importance of FSH in human follicular development. These results provide an opportunity for quantitative studies on factors regulating folliculogenesis in the human and a novel future direction for human IVF. PMID- 8458498 TI - Interleukin-1 type I receptor messenger ribonucleic acid expression in human endometrium throughout the menstrual cycle. AB - OBJECTIVE: To investigate the messenger ribonucleic acid (mRNA) expression of interleukin-1 (IL-1) type I receptor in the endometrial tissue of normal patients during the menstrual cycle. DESIGN: Prospective longitudinal study. SETTING: Department of Obstetrics and Gynecology, Stanford University Medical Center, Stanford, California. PATIENTS: Twenty fertile women between 19 and 41 years of age underwent hysterectomy for benign reasons (n = 9) and laparoscopy for tubal ligation (n = 11). In all cases, endometriosis was not visualized. INTERVENTIONS: Endometrial biopsy using the Novak curette was obtained at the time of surgery. MAIN OUTCOME MEASURE: Total RNA extracted from unfractioned endometrial tissue was analyzed on Northern blots by using specific complementary deoxyribonucleic acid probes. RESULTS: We found IL-1 type I receptor mRNA expression in endometrial tissue throughout the entire menstrual cycle. However, IL-1 type I receptor mRNA levels were significantly higher during both early and late luteal phases than follicular and midluteal phases. CONCLUSIONS: Our results demonstrate the presence of the IL-1 system in the human endometrium and that the receptor is regulated throughout the menstrual cycle with a 4.1-fold increased expression of the IL-1 receptor gene in the early luteal phase compared with preovulatory endometrium. PMID- 8458499 TI - Effects of a 1-year treatment with a low-dose combined oral contraceptive containing ethinyl estradiol and cyproterone acetate on glucose and insulin metabolism. AB - OBJECTIVE: To study the effects of the slightly estrogen-dominant monophasic low dose oral contraceptive (OC) Diane-35 (Schering AG, Berlin, Germany) (35 micrograms ethinyl estradiol [EE2] + 2 mg cyproterone acetate, a 17 alpha hydroxyprogesterone derivative [17-OHP]) on glucose and insulin metabolism. DESIGN: Seven healthy young women were investigated by using the euglycemic hyperinsulinemic glucose clamp technique (insulin delivery rate = 100 mU/kg per hour for 120 minutes). This test was performed, after an overnight fast, during the last 7 days of a spontaneous cycle and within the last 5 days of pill intake during the sixth and twelfth cycle of a continuous treatment with Diane-35 in each subject. RESULTS: The three indexes measuring the insulin-induced glucose disposal during the clamp (glucose infusion rate, glucose metabolic clearance rate, and glucose infusion rate divided by plasma insulin plateau levels) were not significantly affected by Diane-35. In contrast, the metabolic clearance rate of the exogenous insulin infused during the clamp tended to be slightly increased with Diane-35 (significant after 6 but not after 12 cycles). CONCLUSION: These results suggest that a 1-year treatment with the OC Diane-35, which contains EE2 + a 17-OHP rather than a 19-nortestosterone derivative as the progestogen compound, does not significantly alter peripheral (presumably muscular) insulin sensitivity but slightly increases insulin (presumably hepatic) clearance. PMID- 8458500 TI - Effect of a gonadotropin-releasing hormone agonist on luteinizing hormone receptors and steroidogenesis in ovarian cells. AB - OBJECTIVE: To examine the effect of a gonadotropin-releasing hormone agonist (GnRH-a), leuprolide acetate (LA), on human chorionic gonadotropin/luteinizing hormone (LH) receptors content and progesterone (P) and estradiol (E2) production in cultured granulosa or luteal cells. DESIGN: Prospective. SETTING: Private Fertility Clinic and National Research Institute. PATIENTS: Twenty patients undergoing in vitro fertilization or gamete intrafallopian transfer programs. RESULTS: Human chorionic gonadotropin/LH receptors in human granulosa cells increased after 48 hours of culture, and LA inhibited such effect. Leuprolide acetate, 1 ng/mL, in the cultures produced an increase in P production. On the contrary, LA inhibited E2 production. Additionally, the in vivo effect of LA (2 micrograms/rat per 7 days) was studied in corpus luteum of superovulated rats. Luteal cells from LA-treated rats in culture produced lower P than the controls but showed an increase in aromatase activity. Luteal LH receptors declined after 48 hours of culture with LA. CONCLUSION: The high doses of gonadotropin necessary to induce ovarian hyperstimulation when GnRH-a is administered could be related with an inhibitory effect of these agonists on LH receptors and aromatase activity. PMID- 8458501 TI - Hormonal profiles of early gestations with abnormal karyotype. AB - OBJECTIVE: To describe the hormonal profiles of chromosomally abnormal pregnancies during the first trimester. DESIGN: A prospective study from 1984 through 1990 in which infertility patients who conceived were monitored weekly with serum E2, P, and beta-hCG levels. SETTING: The infertility practice at Rush Presbyterian-St. Luke's Medical Center in Chicago, Illinois. PATIENTS: Study included 15 women who had dilatation and curettage for first trimester fetal losses with confirmed abnormal karyotype, 6 women with chromosomally normal male abortuses, and 60 consecutive women whose pregnancies yielded normal term infants. RESULTS: After natural conception, E2 demonstrated a moderate rise in both normal and chromosomally abnormal pregnancies to approximately 300 pg/mL by day 29 (6 weeks of gestation). In normal gestations, E2 continued a steady increase to exceed the level of 1,000 pg/mL by day 64 (11 weeks of gestation). In chromosomally abnormal pregnancies, the mean E2 plateaued and remained at approximately 200 pg/mL until fetal demise was noted. In stimulated conceptions, the rise of E2 was sharp and early (1,200 pg/mL by day 29); in normal pregnancies, E2 steadily increased to an average of 1,400 pg/mL by the end of the first trimester, whereas in karyotypically abnormal gestations, E2 declined to approximately 200 pg/mL by day 64. In pregnancies yielding a male abortus, a sharp decline and plateau at 800 pg/mL by day 56 (10 weeks of gestation) was observed. In both natural and stimulated normal pregnancies, hCG levels first demonstrated a linear rise, followed by a curvilinear increase from day 29 until day 56, with a peak of approximately 110,000 mIU/mL. The beta-hCG in chromosomally abnormal pregnancies, as well as in pregnancies yielding a male abortus, was characterized by a slow and gradual rise to a maximum of 40,000 mIU/mL, which remained relatively linear until day 64 when fetal demise was detected in all cases. Progesterone level data were excluded from analysis because of frequent P supplementation. CONCLUSIONS: There were significant differences in the hormonal profiles of chromosomally normal and abnormal pregnancies. Serial measurements of serum E2 and beta-hCG from the 6th week of gestation may be useful in predicting an abnormal karyotype sooner than other current diagnostic tests. PMID- 8458502 TI - Efficiency of polymerase chain reaction assay for cystic fibrosis in single human blastomeres according to the presence or absence of nuclei. AB - OBJECTIVE: To amplify by polymerase chain reaction (PCR) assay the region of the most common mutation of cystic fibrosis (CF) in human blastomeres. DESIGN: Blastomeres were isolated from two- to eight-cell tripronucleate embryos. The nuclear status of blastomeres was recorded by light microscopy (LM) and by fluorescence microscopy after vital labeling with the fluorochrome Hoechst 33342 (H-33342; Sigma, Brussels, Belgium). In each blastomere the region around the delta F508 mutation site was amplified by two PCRs with nested primers. SETTING: Research units of the Centres for Reproductive Medicine and Medical Genetics of the Dutch-speaking Free University of Brussels, Belgium. RESULTS: The presence of a nucleus by LM in 118 of 160 blastomeres was always confirmed by fluorescence microscopy, and in 10 additional blastomeres the nucleus was only visible by fluorescence microscopy. In the PCR assay all blanks were negative and in nucleate blastomeres (assessed by LM) the amplification rate was 96%. After staining with Hoechst dye the percentage of amplification was 71% or 91% if PCR was performed 2 hours or 20 hours after coloration. CONCLUSION: Efficient preimplantation diagnosis for CF on blastomeres requires assessment of nuclear status by LM and vital staining on blastomeres that are anucleate by LM. PMID- 8458503 TI - Presence of sperm in the perivitelline space predicts fertilization rate after partial zona dissection. AB - OBJECTIVE: To examine the association of the number of spermatozoa present in the perivitelline space and sperm parameters with fertilization after partial zona dissection in male factor patients. DESIGN: Partial zona dissection was applied in 62 couples (84 cycles). A total of 524 oocytes underwent partial zona dissection (1/8 of the zona circumference) (partial zona dissection group) and 171 sibling oocytes were not manipulated (control group). A total of 326 manipulated oocytes were examined for the presence of spermatozoa in the perivitelline space. SETTING: University-based in vitro fertilization (IVF) program. PATIENTS: Fifty-four (87%) couples had at least one complete failure of fertilization, and 8 (13%) couples had low fertilization rate (< 10%) in previous routine IVF attempts. MAIN OUTCOME MEASURES: Fertilization rate, cleavage rate, and the number of spermatozoa present in the perivitelline space after partial zona dissection. RESULTS: Monospermic and polyspermic fertilization rates were 22.3% and 6.7% in the partial zona dissection oocytes and 8.8% and 0.6% in the nonmanipulated oocytes, respectively. The cleavage rate was similar in the partial zona dissection and control group (69.2% and 66.6%, respectively). A total of 81 partial zona dissection embryos and 10 nonmanipulated embryos were transferred to the uterus of 34 women (39 cycles), resulting in four pregnancies. In 46% (18 of 39) of the patients who had both partial zona dissection and control oocytes, only the manipulated oocytes fertilized. In only 48.8% of partial zona dissection oocytes, spermatozoa were detected in the perivitelline space; in this group of oocytes the fertilization rate was 56.6%. Sperm count and morphology were not clearly correlated with the outcome of partial zona dissection. CONCLUSIONS: The partial zona dissection technique enhances fertilization of subfertile sperm. However, the low efficiency of the procedure, apart from being associated with a high polyspermic rate, is related to the failure of sperm to traverse the slit in the zona pellucida in approximately one half of the manipulated oocytes. PMID- 8458504 TI - Sperm characteristics and outcome of human assisted fertilization by subzonal insemination and intracytoplasmic sperm injection. AB - OBJECTIVE: To investigate the influence of sperm characteristics on the treatment by subzonal insemination (SUZI) and intracytoplasmic sperm injection of couples with severe male infertility. DESIGN: A retrospective analysis of 300 consecutive cycles of assisted fertilization concerning 202 infertile couples was performed. One hundred fifty-three couples underwent 362 unsuccessful IVF cycles, whereas on 49 couples IVF was not performed because of poor sperm characteristics. SETTING: Procedures were performed in an institutional research environment. PATIENTS, PARTICIPANTS: Couples in which the male partner was the presumed cause of repeated failure to achieve conception by IVF or in which seminal parameters were unacceptable for IVF. INTERVENTIONS: Three hundred transvaginal oocyte retrievals were performed after superovulation by GnRH agonist and gonadotropins. MAIN OUTCOME MEASURES: After SUZI and intracytoplasmic sperm injection the following parameters were evaluated: fertilization, cleavage, pregnancy, and implantation rates in relation to the sperm parameters and the proportion of acrosome-free spermatozoa after different treatments. RESULTS: Normal fertilization occurred in 18% of the oocytes treated by SUZI and in 44% after intracytoplasmic sperm injection. Only the treatment by electroporation showed a positive correlation with the fertilization rate. Fourteen pregnancies were obtained after SUZI, 8 pregnancies after intracytoplasmic sperm injection, and 8 pregnancies after a combination of the two procedures. A score calculated from the sperm parameters after selection correlated with the fertilization obtained after SUZI, whereas a score calculated from the parameters before sperm selection correlated with the pregnancy rate. Sperm morphology influenced the implantation rate of the embryos obtained with these two procedures. CONCLUSIONS: Intracytoplasmic sperm injection and SUZI can successfully treat couples who fail IVF or who cannot benefit from IVF. Different treatments can be applied to semen samples to increase the number of acrosome-reacted spermatozoa. The few significant relations found between sperm characteristics and the outcome of assisted fertilization cannot predict the outcome. PMID- 8458505 TI - Transvaginal versus laparoscopic gamete intrafallopian transfer: a case controlled retrospective comparison. AB - OBJECTIVE: To compare pregnancy rates (PRs) obtained by transvaginal ultrasound (US)-guided GIFT with PRs from conventional laparoscopy-based GIFT. DESIGN: Retrospective case-controlled study. SETTING: Large, private assisted conception service. PATIENTS: Twenty consecutive cycles of transvaginal GIFT, each matched with three cycles of laparoscopic GIFT on the basis of patient age, number of previous unsuccessful attempts at GIFT, number of eggs transferred, and total number of eggs obtained. MAIN OUTCOME MEASURE: Probability of clinical pregnancy. RESULTS: The PR from transvaginal GIFT was 20.0% (95% confidence limits 13% to 27%), compared with a PR from laparoscopic GIFT of 35.0% (23% to 50%). CONCLUSION: Transvaginal GIFT with present techniques seems to be less effective than laparoscopic GIFT, but it can be considered as a practical alternative to ovarian stimulation and intrauterine insemination and to peritoneal ovum-sperm transfer. PMID- 8458506 TI - Gamete intrafallopian transfer with spinal anesthesia. AB - OBJECTIVE: To investigate the feasibility of performing GIFT under spinal anesthesia administered through a thin (27-gauge) needle. DESIGN: Prospectively studied case series. SETTING: A tertiary care center staffed by a 260 physician multispecialty group. PATIENTS: Twenty-seven consecutive fertility patients underwent 28 laparoscopic GIFT procedures, electing to receive spinal anesthesia administered through a thin (27-gauge) needle. INTERVENTIONS: Laparoscopic GIFT and thin-needle spinal anesthesia. MAIN OUTCOME MEASURES: Assessment of anesthetic complications and reproductive outcome. RESULTS: Satisfactory anesthesia was obtained in 27 of the 28 cases (96%). One patient required additional general anesthesia because of failed spinal anesthesia. All patients were discharged from the hospital on the day of surgery and no postdural headache, persistent back pain, meningitis, or neurological deficit was reported on a 7-day follow-up. Of the 12 clinical pregnancies (43%), 9 ongoing/delivered pregnancies occurred (32%). Six patients had livebirths, and three patients have ongoing second or third trimester pregnancies; there were three spontaneous abortions. CONCLUSIONS: Spinal anesthesia administered through a 27-gauge needle is an attractive option for laparoscopic GIFT. The risk of serious morbidity because of an anesthetic-related complications may be reduced, and the oocytes are not exposed to the potentially deleterious effects of the drugs associated with general anesthesia. PMID- 8458507 TI - Human menopausal gonadotropin during in vitro maturation of human oocytes retrieved from small follicles enhances in vitro fertilization and cleavage rates. AB - OBJECTIVES: To compare the IVF rates of oocytes retrieved from small follicles (< 2 mL in volume) with those of oocytes retrieved from large follicles and to test the effect of adding gonadotropins to the IVF medium on the fertilization rates of oocytes from small follicles. DESIGN: Oocytes were retrieved with endovaginal ultrasound (US) guidance from patients undergoing infertility treatment in our IVF program. Oocytes were grouped according to the volume of the originating follicle and subjected to our routine procedure for IVF. HMG was added to the IVF medium for some of the oocytes from small follicles. SETTING: Toronto Fertility and Sterility Institute is affiliated with the University of Western Ontario and University of Toronto and is equipped for RIA, endovaginal US monitoring and oocyte retrieval, and for processing and culturing gametes and embryos. PATIENTS: Infertile patients admitted to our IVF program. INTERVENTIONS: Patients underwent ovarian stimulation with hMG before oocyte retrieval. No other interventions were introduced to the processing and culturing the gametes and embryos except the addition of hMG to the medium of some of the small follicle-originated oocytes with the informed consent from the patients. MAIN OUTCOME MEASURES: Rates of fertilization, cleavage of the fertilized embryos before replacement, and meiotic status of some of the oocytes from small follicles. RESULTS: Most of the oocytes from small follicles did not complete the first meiotic division; they had low rates of fertilization and cleavage compared with oocytes from large follicles, and these rates were improved by the addition of hMG to the IVF medium. CONCLUSIONS: Oocytes from small follicles are probably less mature and require a more physiological environment to achieve normal rates of fertilization and cleavage. PMID- 8458508 TI - Human sperm fertilizing potential in vitro is correlated with differential expression of a head-specific mannose-ligand receptor. AB - OBJECTIVE: To determine whether different patterns of surface expression of mannose-ligand binding sites are correlated with capacitation and predictive of the ability of human sperm to recognize and fertilize eggs in vitro. DESIGN: Analysis of motile sperm populations (from fertile donors, males presenting for routine semen analysis, and men undergoing IVF) before and after incubation in capacitating media. SETTING: Patients from an infertility practice at a major university hospital. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The mannose ligand-binding capacity of sperm populations were initially assayed by solid phase mannosylated polyacrylamide bead binding studies. Sperm surface D-mannose binding sites thus detected were localized and visualized by fluorescence microscopy after reaction with a mannosylated fluorescein isothiocyanate-labeled neoglycoprotein probe. Results were correlated with acrosomal status, reproductive histories, and IVF outcomes. RESULTS: The percent of sperm with head directed surface expression of a mannose-specific receptor was increased in fertile donors and males exhibiting normal fertilization in IVF after incubation in albumin-supplemented Ham's F-10 medium (GIBCO Laboratories, Grand Island, NY). In normospermic males exhibiting zona binding failure in IVF, mannose-specific receptor was observed over the head surface of few incubated sperm. CONCLUSIONS: The appearance of D-mannose-ligand binding sites on the surface of heads of human spermatozoa is associated with zona binding ability in IVF and is a putative determinant in human gamete recognition and fertilization. PMID- 8458509 TI - Effect of lysoplatelet-activating factor on human sperm fertilizing ability. AB - OBJECTIVE: To evaluate the penetration rates in the hamster zona-free oocyte sperm penetration assay (SPA) after exposure of spermatozoa to lysoplatelet activating factor (LPAF) and lysophosphatidyl choline (LPC). DESIGN: Washed human spermatozoa were exposed to 100 microM of LPAF or LPC, followed by the assessment of their fertilizing ability using the SPA. The percentage of penetration, the sperm binding in the SPA, the percentage of motile spermatozoa, and the acrosome reaction rates were quantified. SETTING: Private research and university laboratories. PATIENTS, PARTICIPANTS: Fresh and frozen semen samples from fertile donors with proven fertility were used as well as fresh semen from infertile patients attending a fertility clinic. All the infertile patients had abnormal semen analysis. INTERVENTIONS: Human spermatozoa were incubated for 90 minutes in the presence or absence of LPAF or LPC at 100 microM with 0.3% albumin in Ham's F 10 (GIBCO, Dorval, Quebec, Canada), and their fertilizing ability was evaluated using the SPA. The effect of these lysophospholipids on the percentage of acrosome reaction was evaluated with a fluorescent microscopy technique. RESULTS: The penetration rates of the SPA in male factor increased significantly from 3% +/- 6% with controls to 19% +/- 9% and 34% +/- 22% after incubation with LPC and LPAF, respectively. Sperm-oocyte binding was not significantly increased in this group. Sperm penetration assay penetration rates were also increased in fertile cryopreserved spermatozoa with LPC and LPAF. In this group, the acrosome reaction was significantly increased from 2% +/- 1% in controls to 10% +/- 6% and 8% +/- 3% after incubation with LPC and LPAF, respectively. CONCLUSION: Lysoplatelet activating factor and LPC independently increased the penetration rate of spermatozoa and the percentage of acrosome reaction. Lysophosphatidylcholine and LPAF may be beneficial in the treatment of spermatozoa with male factor infertility and may increase fertilization rates in IVF. PMID- 8458510 TI - Chemoattractant agents and nerve growth factor stimulate human spermatozoal reactive oxygen species generation. AB - OBJECTIVE: To investigate the ability of N-formyl-methionyl-leucyl-phenylalanine (f-MLP), complement 5a (C5a), and nerve growth factor (NGF) to stimulate human spermatozoal reactive oxygen species generation in fertile and infertile patients. DESIGN: Prospective, controlled study measuring human spermatozoal reactive oxygen species generation after addition of f-MLP, C5a, or NGF. SETTING: A large health maintenance organization. PATIENTS, PARTICIPANTS: The fertile group consisted of 14 men with established fertility and normal bulk semen parameters. The infertile group was comprised of 8 men who were infertile after > 18 months of unprotected sexual intercourse. INTERVENTIONS: The sperm samples were subjected to four test conditions: f-MLP stimulation, C5a stimulation, NGF stimulation, and no stimulation (control). MAIN OUTCOME MEASURE: Reactive oxygen generation was measured over a 15-minute period using the method of chemiluminescence. RESULTS: In both the fertile and infertile groups, reactive oxygen species generation was significantly enhanced by f-MLP, C5a, and NGF compared with controls. No significant difference in f-MLP- and C5a-stimulated reactive oxygen production was demonstrated between the infertile and fertile groups; however, there was a significant difference in reactive oxygen generation between infertile and fertile subjects when stimulated with NGF. CONCLUSIONS: The current study represents the first report of f-MLP-, C5a-, and NGF-stimulated reactive oxygen species generation by human spermatozoa. Nerve growth factor enhanced reactive oxygen species production to a greater extent in infertile subjects compared with fertile subjects. This points to a possible NGF-mediated biochemical defect in the sperm of infertile patients. PMID- 8458511 TI - Detection of interleukin-8 (IL-8) in seminal plasma and elevated IL-8 in seminal plasma of infertile patients with leukospermia. AB - OBJECTIVE: To determine if interleukin-8 (IL-8) is a normal constituent of seminal plasma and if leukospermia is a factor determining its elevation. DESIGN: Seminal plasma from 58 men obtained by masturbation was examined for the presence of IL-8 using an IL-8 specific sandwich ELISA. Semen samples were obtained from 34 infertile men without leukospermia, 10 infertile men with leukospermia, and 14 proven fertile men. The correlation of amount of IL-8 in seminal plasma with some spermiogram parameters and the amount of polymorphonuclear (PMN) elastase was statistically evaluated. RESULTS: Immunoreactive IL-8 was observed in the seminal plasma of all 58 subjects. The IL-8 titer in seminal plasma of patients with leukospermia (6.16 +/- 0.82 micrograms/L) was significantly higher than that in seminal plasma of patients without leukospermia (2.35 +/- 0.34 micrograms/L) and fertile men (1.64 +/- 0.29 micrograms/L). There was a high degree of correlation between PMN elastase and IL-8 levels in seminal plasma. CONCLUSIONS: These findings demonstrate IL-8 to be in seminal plasma and elevated IL-8 levels in infertile patients with leukospermia. PMID- 8458512 TI - The efficacy and safety of zona pellucida drilling by a 193-nm excimer laser. AB - OBJECTIVE: To examine the efficiency of argon fluoride excimer laser drilling of the zona pellucida of mouse oocytes in improving in vitro fertilization (IVF) at low sperm concentrations and to assess its safety. DESIGN: Oocytes obtained from (Balb/c x C57BL6)CB6F1 female mice were drilled by laser and divided into two groups: group I (89 oocytes) were inseminated with 10(5) sperm cells/mL, and group II (94 oocytes) were inseminated with 10(6) sperm cells/mL. Both groups' fertilization rate and development in vitro was compared with control oocytes that underwent the same preparation steps but no drilling (94 and 88 oocytes for group I and group II, respectively). MAIN OUTCOME MEASURES: The fertilization rate and the development in vitro of the laser-drilled groups is compared with that of the control. In addition, in vivo development of embryos generated from laser-drilled oocytes after transfer to pseudopregnant recipients is assessed. RESULTS: For both sperm concentrations, laser drilling significantly enhanced fertilization over control (67% versus 31% at 10(5) sperm cells/mL and 90% versus 54% at 10(6) sperm cells/mL). The development into the blastocyst stage after 96 hours of incubation was similar for both the laser-drilled and control groups at any sperm cell concentration. However, complete hatching at this point was significantly enhanced by the drilling procedure. Normal litters were obtained from the transfer of embryos developed from zona-drilled oocytes into pseudopregnant recipients. CONCLUSIONS: Excimer laser drilling enhanced IVF at low sperm cell concentration. The procedure is safe and did not interfere with embryo development in vitro or in vivo. PMID- 8458513 TI - Baboon corpus luteum: the effect of melatonin on in vitro progesterone production. AB - OBJECTIVE: To determine the effect of melatonin on baboon corpus luteum (CL) cell progesterone (P) production. DESIGN: Five baboon CL obtained during the midluteal phase by luteectomy were dissociated using collagenase, and incubations were performed (50,000 cells per plate) in quadruplicate for 3 hours at 37 degrees C with melatonin (0.001 to 1.0 ng/mL) (basal) or with melatonin and 10 IU of human chorionic gonadotropin (hCG) (hCG-stimulated). Total P was measured by a specific radioimmunoassay. MAIN OUTCOME MEASURES: Progesterone concentrations measured in the presence and absence of melatonin and hCG. RESULTS: Melatonin (0.01 to 1.0 ng/mL) inhibited basal P production in all the CL (41.8 +/- 9.9 ng P without melatonin compared with 32.2 +/- 2.0 ng P, 28.4 +/- 2.1 ng with 0.01 and 1.0 ng/mL melatonin, respectively). Human chorionic gonadotropin-stimulated P production was significantly inhibited with as little as 0.01 ng of melatonin (150.8 +/- 11.4 ng with 10 IU hCG versus 120.3 +/- 6.4 ng with 10 IU hCG and 1.0 ng melatonin). The degree of inhibition in the hCG-stimulated cells was greater than in the nonstimulated cells. Melatonin at a concentration of 0.001 ng/mL did not affect P production in both stimulated and nonstimulated cells. Serotonin in similar concentrations had no effect on luteal cell P production. CONCLUSION: These findings indicate that melatonin exerts a suppressive effect on baboon dispersed luteal cell P production and thus may play a role in luteal function. PMID- 8458514 TI - A comparative evaluation of Poloxamer 407 and oxidized regenerated cellulose (Interceed [TC7]) to reduce postoperative adhesion formation in the rat uterine horn model. AB - OBJECTIVES: To determine if Poloxamer 407 (poloxamer, Pluronic F-127; BASF Wyandotte Corp., Parsippany, NJ) is as effective as Interceed(TC7) (Ethicon, a Johnson and Johnson company, Sommerville, NJ) in preventing postoperative adhesion formation using the rat uterine horn model and to determine if the presence of blood or lactated Ringer's solution affects the effectiveness of Poloxamer 407. DESIGN, SETTING, PARTICIPANTS: Sprague-Dawley white rats, weighing 225 to 250 g in a conventional laboratory setting. The left or right sidewall was randomly assigned to receive no treatment (control), Interceed(TC7), or poloxamer. INTERVENTIONS: Each uterine horn and ipsilateral sidewall was subjected to a standardized lesion of denudation. To evaluate the barrier agents in the presence of blood, a sidewall vessel was ligated and a thrombus allowed to form. To evaluate the effectiveness of lactated Ringer's solution, 10 mL was injected intraperitoneally after abdominal closure. MAIN OUTCOME MEASURES: Degree of adhesion formation was evaluated 14 days after surgery. RESULTS: The adhesion score for the poloxamer-treated animals was significantly lower than its control. Interceed(TC7) did not reduce adhesion formation as compared with its control. In animals that received both poloxamer and Interceed(TC7) on either side, the poloxamer-treated sides had a significantly lower adhesion score than Interceed(TC7)-treated sides. The presence of blood and lactated Ringer's reduced the adhesion-reducing properties of poloxamer. CONCLUSION: In this model, poloxamer is more effective than Interceed(TC7) in the prevention of postoperative adhesion formation. These findings also suggest that the presence of blood compromises the effectiveness of poloxamer to prevent postoperative adhesion formation, therefore requiring complete hemostasis before poloxamer's application. Lactated Ringer's instillation was ineffective in reducing adhesion formation on the control or poloxamer-treated sidewall. PMID- 8458515 TI - Interleukin-6 in experimental endometriosis. AB - OBJECTIVE: To measure the concentration of interleukin-6 (IL-6) in peripheral serum and conditioned media (CM) of macrophages collected from the peritoneal cavity in rats before and after surgically inducing endometriosis. DESIGN: Adult female rats (n = 50) underwent autotransplantation of adipose tissue or uterine squares. Peritoneal cavity macrophages were collected at the initial laparotomy. Rats were killed 4 or 8 weeks later, and peripheral serum and peritoneal cavity macrophages were collected. Macrophages were cultured for 48 hours, and the IL-6 concentrations in CM and serum were measured using the B9 hybridoma cell line bioassay. RESULTS: Serum IL-6 levels were significantly increased at 4 weeks but not at 8 weeks in rats receiving endometrial implants. Interleukin-6 production by macrophages from rats with endometrial implants at 4 or 8 weeks was not significantly different from baseline or from rats receiving adipose tissue implants. CONCLUSION: The increased serum IL-6 levels at 4 but not 8 weeks after surgical induction of endometriosis suggest that IL-6 may be involved in the initial development of endometriosis in this experimental model. PMID- 8458516 TI - Effects of growth hormone on follicle growth, oocyte maturation, and ovarian steroidogenesis. AB - OBJECTIVES: To assess the effects of GH on follicle growth, oocyte maturation, ovulation, and ovarian steroidogenesis. DESIGN: In vitro perfused rabbit ovary. INTERVENTIONS: The rabbit ovaries were perfused with medium alone, with GH at 1, 10, 100, or 200 ng/mL, or with 50 IU hCG for 12 hours. MAIN OUTCOME MEASURES: The follicle diameter, the percent change in follicle diameter, the percentage of oocytes achieving germinal vesicle breakdown, and the production of P and E2 by the perfused rabbit ovaries. RESULTS: The addition of GH to the perfusate increased the follicle diameter at 12 hours after perfusion in a dose-dependent manner. The percent change in follicle diameter in GH-treated ovaries did not differ significantly from that in hCG-treated ovaries at each time point of perfusion. However, ovulation did not occur in either the control ovaries or the experimental ovaries treated with GH. Exposure to GH at a concentration of > 10 ng/mL significantly stimulated the resumption of meiosis, as compared with the contralateral control ovaries. Although the concentration of P in the perfusate did not differ significantly between GH-treated and control ovaries, GH stimulated E2 production by the perfused rabbit ovaries in a dose-dependent manner. CONCLUSIONS: Growth hormone acts on the rabbit ovary to stimulate follicle growth, oocyte maturation, and ovarian E2 production. PMID- 8458517 TI - Tubal damage after intratubal methotrexate treatment. AB - We report on a case of seriously hampered tubal repair 6 months after local MTX treatment. Histopathological examination showed destruction of tubal mucosa and remnants of the EP. PMID- 8458518 TI - Circulating CA-125 levels in superovulated women are mainly derived from the ovaries. AB - A prospective study was designed to determine the individual contribution of the ovaries and the endometrium to total circulating levels of CA-125. Luteal phase CA-125 levels were measured in five women superovulated before and after vaginal hysterectomy performed for pelvic relaxation. The difference in the preoperative and postoperative luteal CA-125 levels of superovulated cycles were similar, suggesting a mainly ovarian source for the antigen although endometrial and other sites of contribution cannot be excluded in view of the small number of patients studied. PMID- 8458519 TI - Urinary follicle-stimulating hormone as a biological marker of ovarian toxicity. AB - Reproductive senescence has not been adequately explored as a possible end point for assessing toxicity to the reproductive system. We propose that urinary FSH be used as a biologic marker of ovarian function in women. A urinary marker would facilitate the incorporation of this measure into epidemiologic studies of reproductive toxicity. Although there is some evidence that FSH in serum is a good biologic marker of ovarian reserve, the relationship between serum FSH and urinary FSH has not been adequately explored. We found that urinary FSH and serum FSH were closely correlated in 50 consecutive women seen in clinical practice. PMID- 8458520 TI - Adhesions after resection of ovarian endometriomas. PMID- 8458521 TI - Management of the transfer cycle--after freeze/thaw. PMID- 8458522 TI - Flutamide--effects and side effects. PMID- 8458523 TI - Contribution of glucose/glucose 6-phosphate cycle activity to insulin resistance in type 2 (non-insulin-dependent) diabetes mellitus. AB - It has been suggested that increased glucose/glucose 6-phosphate substrate cycling impairs net hepatic glucose uptake in Type 2 (non-insulin-dependent) diabetes mellitus and contributes to hyperglycaemia. To investigate glucose/glucose 6-phosphate cycle activity and insulin action in Type 2 diabetes we studied eight patients and eight healthy control subjects, using the euglycaemic glucose clamp and isotope dilution techniques with purified [2-3H]- and [6-3H] glucose tracers, in the post-absorptive state and eight patients and five healthy control subjects during consecutive insulin infusions at rates of 0.4 and 2.0 mU.kg-1 x min-1. [2-3H]glucose and [6-3H]glucose radioactivity in plasma samples were determined using selective enzymatic detritiation, allowing calculation of glucose turnover rates for each isotope, the difference being glucose/glucose 6-phosphate cycling. Endogenous glucose production ([6 3H]glucose) was greater in diabetic than control subjects in the post-absorptive state (15.6 +/- 1.5 vs 11.3 +/- 0.4 mumol.kg-1 x min-1, p < 0.05) and during the 0.4 mU insulin infusion (10.1 +/- 1.3 vs 5.2 +/- 0.3 mumol.kg-1 x min-1, p < 0.01) indicating hepatic insulin resistance. Glucose/glucose 6-phosphate cycling was significantly greater in diabetic than in control subjects in the post absorptive state (2.6 +/- 0.4 vs 1.6 +/- 0.2 mumol.kg-1 x min-1, p < 0.05) but not during the 0.4 mU insulin infusion (2.0 +/- 0.4 vs 2.0 +/- 0.3 mumol.kg-1 x min-1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458524 TI - Peroxovanadate but not vanadate exerts insulin-like effects in human adipocytes. AB - Vanadate and peroxovanadate were recently reported to exert maximal or even supramaximal (peroxovanadate) insulin-like effects in rat adipocytes. To evaluate the response in human cells, isolated human adipocytes were exposed to insulin or various concentrations of vanadate (0-10 mmol/l) or peroxovanadate (0-5 mmol/l). Neither vanadate nor peroxovanadate affected 125I-insulin binding and insulin sensitivity. Vanadate exerted no apparent effect on 14C-U-glucose uptake, whereas 0.1 mmol/l peroxovanadate exerted a full insulin-like response (p < 0.001). No additive response was observed by combining either vanadate or peroxovanadate with insulin. Peroxovanadate at 0.1 mmol/l was as effective as insulin in inhibiting isoproterenol-stimulated lipolysis. Neither peroxovanadate nor insulin inhibited lipolysis stimulated by N6-monobutyryl-cAMP, an analogue which is not hydrolysed by the cAMP-phosphodiesterase. It is concluded that peroxovanadate, but not vanadate, elicits a full insulin-like response in human adipocytes. PMID- 8458525 TI - Can the birth of a large infant predict risk for atherosclerotic vascular disease in the mother? AB - We have previously demonstrated that women who had given birth to large infants had a six-fold increased risk of developing Type 2 (non-insulin-dependent) diabetes mellitus compared with a control group matched for age and parity. However, the patients were extremely obese which explained, in part, the increased risk. In the present investigation we studied whether the delivery of large infants correlated with risk factors for atherosclerotic vascular disease other than obesity and diabetes, and therefore could serve as early markers for syndrome X. The study consisted of 73 women who 20-27 years earlier had given birth to large infants weighing 4,500 g or more. Another group of 73 women matched for age, parity and BMI who had delivered infants weighing less than 4,500 g within a 3-month period served as a control group. Of these 73 patient/control pairs, 48 (66%) were able to participate in the investigation. Mean age was 52.2 years (range 40-66 years). No differences were noted for family history of diabetes and medication prescribed for vascular disease between the groups. An oral glucose tolerance test was performed and glucose, insulin and C peptide at 0 and 2 h were estimated. Triglycerides, cholesterol, LDL and HDL cholesterol were analysed at baseline. We found no tendency towards hyperinsulinaemia and hyperglycaemia in the patients and both groups had the same relative increase in levels of insulin and C-peptide. No difference between the groups regarding manifest symptoms of vascular disease, either in blood pressure or in proteinuria were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458526 TI - Insulin sensitivity, insulin secretion and glucose effectiveness in diabetic and non-diabetic cirrhotic patients. AB - In cirrhotic patients with normal fasting glucose levels both insulin insensitivity and a blunted early insulin response to oral glucose are important determinants of the degree of intolerance to oral glucose. It is not known whether the ability of hyperglycaemia per se to enhance glucose disposal (glucose effectiveness) is also impaired. It is also unclear whether overt diabetes is due to: (1) more marked insulin insensitivity; (2) impaired insulin secretion; (3) reduced glucose effectiveness; or (4) a combination of these mechanisms. We used the "minimal model" to analyse the results of a 3-h intravenous glucose tolerance test to assess glucose effectiveness, insulin sensitivity and insulin responses in 12 non-diabetic cirrhotic patients, 8 diabetic cirrhotic patients and 10 normal control subjects. Fasting blood glucose levels were 4.8 +/- 0.2, 7.5 +/- 0.6 and 4.7 +/- 0.1 mmol/l, respectively. Fasting insulin and C-peptide levels were higher in both cirrhotic patient groups compared with control subjects. The glucose clearance between 6 and 19 min after i.v. glucose was lower in both cirrhotic groups (non-diabetic, 1.56 +/- 0.14, diabetic, 0.76 +/- 0.06, control subjects, 2.49 +/- 0.16 min-1%, both p < 0.001 vs control subjects). Serum insulin peaked at 3 and 23 min in the non-diabetic cirrhotic patients and control subjects; both peaks were higher in the non-diabetic cirrhotic patients and showed a delayed return to basal levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458527 TI - Linkage analysis of the glucokinase locus in familial type 2 (non-insulin dependent) diabetic pedigrees. AB - Glucokinase is among the few genes which may play a key role in both insulin secretion and insulin action. Glucokinase is present in pancreatic beta cells where it may have a key role in the glucose sensing mechanism, and it is present in hepatocytes, where it may participate in glucose flux. Glucokinase defects have recently been implicated in maturity-onset diabetes of the young. To examine the hypothesis that glucokinase plays a key role in the predisposition to common familial Type 2 (non-insulin-dependent) diabetes mellitus, we typed 399 members of 18 Utah pedigrees with multiple Type 2 diabetic individuals for two markers in the 5' and 3' flanking regions of the glucokinase gene. Linkage analysis was performed under both dominant and recessive models. We also repeated these analyses with individuals with impaired glucose tolerance who were considered affected if their stimulated (2-h) glucose exceeded age-specific normal levels for 95% of the population. Under several dominant models, linkage was significantly excluded, and under recessive models log of the odds (LOD) score was less than -1. We were also unable to demonstrate statistical support for the hypothesis that a small subgroup of pedigrees had glucokinase defects, but the most suggestive pedigree (individual pedigree LOD 1.8-1.9) ranked among the youngest and leanest in our cohort. We can exclude a major role for glucokinase in familial Type 2 diabetes, but our data cannot exclude a role for this locus in a minority of pedigrees.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458528 TI - Cellular ionic effects of insulin in normal human erythrocytes: a nuclear magnetic resonance study. AB - Elevated erythrocyte cytosolic free calcium, and suppressed free magnesium and pH values are associated with the hyperinsulinaemia and insulin resistance of hypertension, obesity, and Type 2 (non-insulin-dependent) diabetes mellitus. To determine the role of insulin in this process, we utilized 19F- and 31P-nuclear magnetic resonance spectroscopy to study the cellular ionic effects of insulin in vitro on normal human erythrocytes. Insulin elevated cytosolic free calcium levels in a dose- and time-dependent manner. The effect began at 10 microU/ml, peaked at 200 microU/ml, and continued at both the 500 microU/ml and 1000 microU/ml doses. At 200 microU/ml, free calcium levels rose from 24.6 +/- 2.5 nmol/l to a peak value at 120 min of 66.4 +/- 11 nmol/l (p < 0.05 vs basal), levels remaining elevated throughout the incubation (45.7 +/- 5.6 nmol/l at 60 min, and 47.9 +/- 9.1 nmol/l at 180 min, p < 0.05 vs basal, respectively). Similarly, insulin also increased intracellular free magnesium at all time points (basal: 177 +/- 11 mumol/l; 60 min: 209 +/- 19 mumol/l; 120 min: 206 +/- 22 mumol/l; and 180 min: 202 +/- 12 mumol/l; p < 0.05 vs basal at all times). No insulin-induced changes in pH were observed. We conclude: (i) that insulin in physiological concentrations may participate in regulating divalent cations in the mature human erythrocyte, (ii) that insulin per se cannot account for the previously described cellular ionic lesions of hypertension and diabetes, and (iii) that future clinical studies of cell ion metabolism should be conducted in the fasting state, be controlled for ambient circulating insulin levels, or both. PMID- 8458529 TI - A multicentre study of the prevalence of diabetic peripheral neuropathy in the United Kingdom hospital clinic population. AB - A cross-sectional multicentre study of randomly selected diabetic patients was performed using a standardised questionnaire and examination, to establish the prevalence of peripheral neuropathy in patients attending 118 hospital diabetes clinics in the UK. Vibration perception threshold was performed in two centres to compare with the clinical scoring systems. A total of 6487 diabetic patients were studied. 53.9% male, median age 59 years (range 18-90 years). 37.4% Type 1 (insulin-dependent) diabetes mellitus, with a median duration of diabetes 8 years (0-62 years). The overall prevalence of neuropathy was 28.5% (27.4-29.6%) (95% confidence interval) in this population. The prevalence in Type 1 diabetic patients was 22.7% (21.0-24.4%) and in Type 2 (non-insulin-dependent) diabetic patients it was 32.1% (30.6-33.6%). The prevalence of diabetic peripheral neuropathy increased with age, from 5% (3.1-6.9%) in the 20-29 year age group to 44.2% (41.1-47.3%) in the 70-79 year age group. Neuropathy was associated with duration of diabetes, and was present in 20.8% (19.1-22.5%) of patients with diabetes duration less than 5 years and in 36.8% (34.9-38.7%) of those with diabetes duration greater than 10 years. Mean vibration perception threshold measured at the great toe was 21.1 +/- 13.5 SD volts and correlated with the neuropathy disability score, r = 0.8 p < 0.001. In conclusion, diabetic peripheral neuropathy is a common complication associated with diabetes. It increases with both age and duration of diabetes, until it is present in more than 50% of Type 2 diabetic patients aged over 60 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458530 TI - Abnormal distribution of VLDL subfractions in type 1 (insulin-dependent) diabetic patients: could plasma lipase activities play a role? AB - Very low density lipoproteins (VLDL) have an abnormal lipid composition in Type 1 (insulin-dependent) diabetic patients. Since VLDL represent a heterogeneous lipoprotein class, this might be due either to a shift in the distribution or to an abnormal composition of VLDL subclasses or both. In order to investigate these possibilities and to evaluate possible pathogenetic mechanisms, lipid composition (non-esterified and esterified cholesterol, triglycerides, phospholipids) of four VLDL subfractions of decreasing size (A: Svedberg flotation unit [Sf] > 400, B: Sf > 400, B: Sf 175-400, C: Sf 100-175, D: Sf 20-100), isolated by density gradient preparative ultracentrifugation, and plasma post-heparin lipolytic activity (lipoprotein lipase and hepatic lipase) were evaluated in 13 male normolipidaemic insulin-dependent diabetic patients in good glycaemic control (HbAlc 6.9 +/- 0.5%) (mean +/- SEM) and 9 male control subjects matched for age, body mass index and plasma lipid values. Compared to control subjects, diabetic patients showed a reduced total lipid concentration of VLDL of intermediate size (B and C) reaching statistical significance only for VLDL C (0.16 +/- 0.02 vs 0.24 +/- 0.03 mmol/l; p < 0.05). Expressing each VLDL subfraction as percent of the total VLDL lipid concentration, a significant decrease in particles of intermediate size (C) (20.5 +/- 1.6 vs 27.9 +/- 1.5%; p < 0.005) was present, which was compensated by an increase in the smallest ones (D) (50.5 +/- 2.7 vs 37.4 +/- 3.1%; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458531 TI - Lowering of triglycerides by gemfibrozil affects neither the glucoregulatory nor antilipolytic effect of insulin in type 2 (non-insulin-dependent) diabetic patients. AB - Hypertriglyceridaemia and insulin resistance are closely associated but it is unknown whether hypertriglyceridaemia per se contributes to insulin resistance. In the present study we examined whether gemfibrozil, by lowering triglyceride levels, improves the glucoregulatory and antilipolytic action of insulin in Type 2 (non-insulin-dependent) diabetes mellitus. Twenty patients were randomly allocated to receive either placebo or gemfibrozil 1200 mg daily for 12 weeks in a double-blind study. Very low density lipoprotein triglyceride levels decreased in the gemfibrozil group by 42 +/- 12% (p < 0.01). Gemfibrozil had no effect on the diurnal concentration of non-esterified fatty acids (NEFA). At the randomization HbA1c levels were comparable (7.6 +/- 0.3 vs 7.8 +/- 0.2%, NS) and increased slightly both in the gemfibrozil (8.2 +/- 0.4%, p < 0.05) and placebo groups (8.0 +/- 0.3%, NS). Pre- and post-treatment diurnal glucose and insulin concentrations remained unchanged. Basal pre- and post-treatment hepatic glucose production rates were comparable in both groups and similarly suppressed by insulin. Rate of whole body glucose disposal during a low-dose insulin infusion (serum insulin -90 pmol/l) (pre- vs post-gemfibrozil 11.9 +/- 1.1 vs 11.1 +/- 0.7, pre- vs post-placebo 9.9 +/- 1.1 vs 10.8 +/- 0.8 mumol.kg-1.min-1, NS for both) and a high-dose insulin infusion (serum insulin approximately 500 pmol/l) (16.2 +/- 1.7 vs 17.7 +/- 2.7, 17.1 +/- 4.2 vs 17.4 +/- 2.9 mumol.kg-1 x min-1, respectively, NS for both) remained unchanged. Basal pre- and post-treatment NEFA turnover rates were comparable in both groups and similarly suppressed by insulin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458532 TI - Characterization of a third simple tandem repeat polymorphism in the human glucokinase gene. AB - Recent studies have implicated mutations in the glucokinase gene as a cause of early-onset Type 2 (non-insulin-dependent) diabetes mellitus. Two simple tandem repeat DNA polymorphisms have been identified in this gene and used for genetic studies. However, their heterozygosity is relatively low and not all families are informative for linkage with these markers. Here we report the characterization of a third simple tandem repeat polymorphism that can be used for genetic studies. PMID- 8458533 TI - Patients with lipodystrophic diabetes mellitus of the Seip-Berardinelli type, express normal insulin receptors. AB - Lipodystrophic diabetes mellitus of the Seip-Berardinelli type is a syndrome associated with insulin resistance and recessive inheritance. We have examined whether mutations in the insulin receptor are pathogenetic factors in this syndrome. Fibroblasts from three different patients with Seip-Berardinelli's lipodystrophy were tested for insulin binding, and insulin-stimulated receptor autophosphorylation. In addition, the coding region of both alleles of the iinsulin receptor gene was sequenced. No abnormalities in the number of high affinity insulin binding sites, and insulin-stimulated receptor autophosphorylation were detected. The insulin receptor related insulin-like growth factor I receptor also showed no functional changes. DNA sequence analysis of the amplified exons of the insulin receptor gene showed a silent mutation in patient 1 at codon Ser339, changing AGT to AGC. In patient 2 a heterozygous Met for Val substitution at position 985 was detected, which is a rare polymorphism. In patient 3 no mutations, other than described polymorphisms, were observed. These findings demonstrate that the primary genetic lesion in Seip-Berardinelli's lipodystrophy is outside the insulin receptor gene and that an involvement of the insulin-like growth factor I receptor is also unlikely. PMID- 8458534 TI - Increased rat myocardial type VI collagen in diabetes mellitus and hypertension. AB - Diabetic cardiomyopathy, a condition characterized by the accumulation of carbohydrate-containing material surrounding the myocardial small blood vessels, has been studied in alloxan-diabetic normotensive and hypertensive rats. Immunochemical techniques were used to monitor several extracellular matrix constituents present in extracts of cardiac tissue, namely types I, IV and VI collagen, laminin and fibronectin, as well as myosin. These studies have indicated that after induction of diabetes, type VI collagen but none of the other matrix components studied, was significantly increased (from 2.29 +/- 0.04 mg/g in normal to 2.85 +/- 0.18 mg/g in diabetic ventricles, p < 0.01). Hypertension, whether induced by the clipping of one renal artery or genetically determined (spontaneously hypertensive rats), resulted in a similar elevation in type VI collagen (2.71 +/- 0.12 mg/g, p < 0.005 compared to normal rats). In the presence of diabetes plus hypertension the effect was not additive, the type VI collagen level being 2.93 +/- 0.15 (p < 0.001 compared to normal rats). Basement membrane collagen (type IV) in the myocardium appeared to be unaffected by diabetes or hypertension and the myosin contents of the hearts of the four experimental groups were similar. Quantitative determinations indicate that compared to type IV collagen, laminin or fibronectin, type VI collagen represents the major periodic acid-Schiff-reactive extracellular constituent of the rat ventricle. Its preferential increase in the heart in diabetes may provide insight into the molecular mechanisms of the diabetic microvascular disease. PMID- 8458535 TI - Effective and safe translation of intensified insulin therapy to general internal medicine departments. AB - Up to now all published experience with intensified insulin therapy has originated from specialized diabetes centres. However, even in diabetes centres and under research conditions intensification of insulin therapy may substantially increase the risk of severe hypoglycaemia. The aim of the present study was to demonstrate the feasibility of effectively and safely transferring intensified insulin therapy based upon a 5-day in-patient treatment and teaching programme from a University diabetes centre to non-specialized general hospitals. A total of nine general hospitals were recruited; the University diabetes centre served as a reference centre. From each general hospital a nurse and a dietitian were trained as diabetes educators, and a diabetes unit with about 10 beds was organized within each department of internal medicine. A total of 697 consecutively admitted Type 1 (insulin-dependent) diabetic patients (age 26 +/- 7 years, duration of diabetes 8 +/- 7 years) who participated in the programme either in one of the general hospitals (n = 579) or in the reference centre (n = 118) were re-examined after 1, 2 and 3 years. Insulin therapy was intensified to a similar extent in the reference centre and the general hospitals; at the 3-year follow-up about 80% of the patients injected insulin at least three times daily or used continuous subcutaneous insulin infusion (10%), and about 70% reported measuring blood glucose levels more than twice per day. HbA1 levels were lowered (p < 0.0001) to comparable levels, i.e. from 10.6% (reference centre) and 9.9% (general hospital), respectively, at baseline to 9.4% and 9.3%, respectively, at the 3-year follow-up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458536 TI - The Executive Skills Profile: a method for assessing development needs among family medicine faculty. AB - BACKGROUND AND OBJECTIVES: The purpose of this paper is to report on how the Executive Skills Profile, a measure of job demands and employee skills, can be used as a faculty development tool in academic family medicine departments. METHODS: The Executive Skills Profile (ESP) identifies 72 work activities and groups them into 12 scales, each of which is displayed graphically. Faculty identify the work activities that are relevant to their jobs and then identify the personal skills they must have to carry out those work activities. RESULTS: The ESP successfully characterized the job demands and personal skills of one family medicine department. The evaluation showed that overall perceived job demands were greater than the faculty's perceived personal skills, particularly in the areas of interpersonal and behavioral skills. CONCLUSIONS: The ESP can be used to characterize the job demands and personal skills of faculty. PMID- 8458537 TI - Prescription-writing errors and markers: the value of knowing the diagnosis. AB - BACKGROUND AND OBJECTIVES: Duplicate prescription pads are used in many family practice residency programs to monitor prescribing patterns and detect errors in the actual prescription-writing process. This study looked at whether the review of duplicate prescriptions could be enhanced by adding the patient's diagnosis to the prescription. METHODS: The prescription-writing errors of Shaughnessy and Nickel were revised to include prescription-writing markers. These markers were defined as either an indication of use or a duration of therapy that differed from current medical literature or manufacturers' recommendations. Duplicate prescriptions of first-year family practice residents were reviewed for prescription-writing errors and markers before and after an in-service training regarding prescription writing. RESULTS: Following the in-service training, the number of prescriptions containing the patient's diagnosis increased significantly (20% to 61%). Nineteen percent of all prescriptions contained prescription-writing errors. Eight percent of the prescriptions with the patient's diagnosis contained prescription-writing markers. CONCLUSIONS: The addition of the patient's diagnosis to the prescription enhanced the review of duplicate prescriptions. It permitted the evaluation of not only the prescription writing process but also the decision-making process that led to writing the prescription. It also permitted a more thorough evaluation of appropriate drug use. PMID- 8458538 TI - The University of Kentucky's Accelerated Family Practice Residency Program. AB - The University of Kentucky's Department of Family Medicine and the American Board of Family Practice experimented during 1989 and 1990 with the implementation of an accelerated family practice residency program. This pilot program, called the Accelerated Residency Program (ARP), allowed three fourth-year medical students to serve as first-year residents in family practice while simultaneously fulfilling their fourth-year medical school requirements. This allowed the students to complete medical school and residency training in six years instead of seven. Advantages of the program included maintaining clinical skills that might otherwise have been lost during the elective fourth year of medical school, stimulating interest in active learning, earlier entry into a wage-earning position, and an ultimate decrease in the length of the educational process. Disadvantages of the program included having to make important clinical decisions with less training, loss of elective and other training opportunities during the fourth year of medical school, the need for students to make an earlier career/specialty choice, and the possibility that other physicians might perceive graduates of the program as being less well trained. PMID- 8458539 TI - Attitudes of graduating seniors at one medical school toward family practice. AB - BACKGROUND AND OBJECTIVES: Senior medical students' interest in family practice as a career choice has declined in recent years. METHODS: A questionnaire about attitudes toward family practice was mailed to the 1990 graduating class at the University of Maryland (N = 143), and 84 completed questionnaires were returned (59% response rate). RESULTS: Seniors believed that family practice was challenging (89%) and had intellectual content (integrity) comparable to other specialties (81%). Furthermore, students believed that family physicians provided comprehensive care (88%), were not replaceable by other health professionals (86%), and were able to keep abreast with technological medical advances (52%). However, only 4% of the graduating seniors selected family practice as a career. Most students believed that family practice lacked prestige (82%), and about one half (55%) believed that it was too broad in scope. CONCLUSIONS: Lack of prestige, stressful life-style, difficulty in mastering medical knowledge, and poor potential income were the main reasons given by students for not selecting family practice. PMID- 8458540 TI - Collecting data to evaluate the effect of health policies on vulnerable populations. AB - Public health policies often have disproportionate effects on the poor and other vulnerable groups. Standard survey techniques are often difficult to apply to these vulnerable populations, and many data bases systematically omit such individuals. The purpose of this paper is to review our experience in collecting primary survey data from public hospital, mentally ill, HIV-infected, and non English-speaking patients. Important issues in conducting research on these populations include proper selection of subjects and comparison groups and difficulties involved in recruitment and enrollment of subjects. Maintaining longitudinal data on these populations is difficult and often requires tracking, secondary contacts, home visits and community outreach, and the use of organizations, institutions, and networks. Investigators must also pay careful attention to ethical issues involved in conducting research on vulnerable populations. PMID- 8458541 TI - The effect on retirees of losing retirement and health insurance benefits. AB - BACKGROUND AND OBJECTIVES: The recent economic downturn has led to instability in the private health insurance industry. Although loss of medical benefits is assumed to have a negative effect on health, documentation is lacking. LTV Corporation (Ling-Temco-Vought) filed for bankruptcy and interrupted medical insurance for its retirees for six months. METHODS: Using a structured interview format, we surveyed community-living LTV retirees whose medical insurance had been interrupted. We sought to predict health status using a variety of measures. RESULTS: The vast majority of retirees were generally unaffected by the loss of medical benefits. Of the 191 LTV retirees from Youngstown, Ohio, who were interviewed shortly after health benefit loss, 13.8% reported longer-term health effects (continued decline in subjective health status), whereas 8.5% had short term effects (decline followed by return to good or excellent health status). Although 10.5% of workers experienced serious health problems during the crisis, only one worker was unable to pay for health care as a result of the benefits loss. A discriminant analysis yielded excellent results in predicting longer-term deteriorating health status. CONCLUSIONS: Implications for community-oriented primary care service models are discussed, as well as the utility of demographic targeting for retirees losing health benefits. PMID- 8458542 TI - Morbidity in early childhood: family patterns in relation to sex, birth order, and social class. AB - BACKGROUND AND OBJECTIVES: This study investigated family patterns of morbidity in early childhood related to different degrees of severity of morbidity, sex, birth-order position, and social class. METHODS: The study was performed using data collected by the Continuous Morbidity Registration Project of the Department of Family Practice of the Nymegen University in the Netherlands. All recorded morbidity and a number of sociodemographic data (sex, birth order, and social class) were available. The study population included children (783 boys, 730 girls) born in the four practices from 1971 to 1985 and their parents. The children were followed until age five. Morbidity of children during the first five years of life and their parents during the same five years was categorized into three levels of seriousness and 10 morbidity groups. RESULTS: Correlations between morbidity of children and their mothers were high, particularly for nonserious morbidity (0.45-0.49). Correlations between morbidity of fathers and their children were similar for moderate and nonserious morbidity (0.30). Logistic regression analysis showed that the morbidity of the mother was the most important factor in predicting childhood morbidity. CONCLUSIONS: Although morbidity in early childhood was associated with sex, birth order, and social class, the morbidity of the parents, in particular the mother, was by far the most important factor. PMID- 8458543 TI - Incorporating the family into a computerized office registration system. AB - BACKGROUND AND OBJECTIVES: New office computer systems provide physicians with the opportunity to link together the medical records of all members of a family. The purpose of this report is to describe our experience with a computerized family grouping system in a practice of 12,000 patients. METHODS: Using a computerized patient registration system, we developed a six-digit numbering scheme that signified how various members of a household were related to one another. When first instituting the system, we initially linked individuals who shared the same phone number. Subsequently, information was updated and corrected by patients when they came to the office. RESULTS: Costs for the system included the cost of an 80386 computer with a 200 megabyte hard disk and software. In addition, initial entry of patient data cost approximately $0.36 per patient. Costs were lower ($.08 per patient) once the system was established. Several problems were noted in instituting the system, including staff difficulty in adjusting to new routines and errors in data entry and reports. CONCLUSIONS: Computerized patient registration systems permit linkage of medical records and registration information of all individuals in a family or household. Integrating such systems into medical offices requires acceptance of new routines by staff. PMID- 8458544 TI - Development of a Pap smear quality-assurance system in family practice. AB - BACKGROUND AND OBJECTIVES: To improve the effectiveness of cervical cancer screening, quality assurance programs can be designed to ensure that normal Pap smear results are dealt with appropriately and that Pap smears yielding inadequate specimen material are brought to a physician's attention. The objective of this study was to use a new Pap Smear Quality Assurance (PAPQA) system to determine and monitor the performance of physicians in a family practice over a two-year period. METHODS: We developed a PAPQA system designed to gather data and report on: 1) Pap smear adequacy, 2) reporting of abnormal results to physicians, and 3) follow-up of patients who had abnormal Pap smear results. We followed these parameters for two years. RESULTS: Over a two-year period, 2,771 cervical Pap smears were performed, of which 64% were normal. The percentage of Pap smears that yielded adequate specimen material improved from 82% to 91%, an improvement we attributed to feedback the system provided to physicians. Overall, Pap smear results and follow-up appeared in the medical record of 94% of patients who had abnormal findings. However, during the second year, the quality assurance system detected a deterioration in documentation of results and follow-up plans that coincided with moving the practice to a new facility. The operating cost for this program was approximately $950 per year. CONCLUSIONS: Quality assurance programs can effectively monitor physicians' performance in dealing with abnormal Pap smears, can detect deteriorations in performance, and can improve some aspects of performance through feedback reporting to physicians. PMID- 8458545 TI - Is experience lacking in family practice faculty? PMID- 8458546 TI - More on the match. PMID- 8458547 TI - Teaching dermatology: too dependent on dermatologists? AB - BACKGROUND AND OBJECTIVES: Training in dermatology is important for family physicians because skin diseases are common in family practice. METHODS: We performed a national survey of 384 program directors to ascertain the dermatology teaching methods used by family practice residencies. RESULTS: Based on an 83% response rate, most programs used dermatology lectures (84%), preceptorship rotations in a dermatologist's office (79%), and dermatology specialty clinics (51%) to teach residents dermatological skills. More than half of the programs using these teaching methods relied exclusively on dermatologists to be primary instructors. Despite the substantial dependence on dermatologists, one third of responding programs reported difficulty obtaining teaching support from dermatologists. CONCLUSIONS: A substantial proportion (33%) of family practice residency programs have difficulty in obtaining support from dermatologists to teach their residents. Further research should be conducted to determine the effect of this finding on dermatologic instruction in family practice residency programs. PMID- 8458549 TI - On the importance of religious variables. PMID- 8458550 TI - Sharing solutions in international family medicine. PMID- 8458548 TI - A community-oriented primary care experience for medical students and family practice residents. AB - BACKGROUND AND OBJECTIVES: Medical students and residents are more likely to understand the health needs of a community if they have community-based practical experience during their training. This report describes a community-oriented educational experience for medical students and family practice residents in rural North Carolina. METHODS: Medical students and residents from the University of North Carolina at Chapel Hill and residents from Asheville spend one month in a small community in western North Carolina. During the month-long experience, these trainees live in the community and provide clinical care to patients. They also meet with local health officials, service agencies, and community organizations to learn about the community's health system. The trainees then prepare a written report about the community's health system, a community health problem identified by the trainee, and a proposal to solve the problem. RESULTS: Trainees report that the rotation provides a unique opportunity to understand the health system of a community. Some of the trainee-proposed solutions to problems have been implemented by community leaders. CONCLUSION: A community-oriented primary care rotation can provide students and residents with an important understanding of the health system and health problems of a community. PMID- 8458551 TI - Exercise and the elderly. PMID- 8458552 TI - An international perspective on academic development in family medicine. PMID- 8458553 TI - Not what I say, but what I do: limitations of introspective causal reports. PMID- 8458554 TI - Community advocacy, physician roles, and medical education. PMID- 8458555 TI - Doing well by doing good: family medicine teaching in the preclinical years. PMID- 8458556 TI - Does teaching by family physicians in the second year of medical school increase student selection of family practice residencies? AB - BACKGROUND AND OBJECTIVES: Most educators feel that early instruction by family physician teachers increases the probability of students selecting family practice residencies. METHODS: To examine this hypothesis, a retrospective cohort study was performed to evaluate residency selection of students who received their second-year Introduction to Clinical Medicine (ICM) teaching either from family physicians or other specialists (most commonly, internists). RESULTS: For the 971 students who could be followed to residency, 13.6% of those having family physicians as instructors and 15.7% of those having other specialists as instructors chose family practice residencies. The difference is not significant. CONCLUSION: It is probable that the effect of having a family physician as a second-year ICM instructor is not significant enough to be detected by a study of this size and is simply "washed out" by other factors. It is also possible that no positive effect of second-year teaching by family physicians on residency selection exists. PMID- 8458557 TI - The effect of a student summer assistantship program in family medicine on specialty selection. AB - BACKGROUND AND OBJECTIVES: Stimulating medical students' interest in family practice is a goal of family medicine education. Summer assistantship programs have been instituted to help address this issue. METHODS: This study evaluated the results of residency program selection for participants in a family medicine summer assistantship program during a five-year period. Students who applied for the assistantship but were not accepted were used as a comparison group to measure student interest in family medicine. Additional comparisons were made with students who neither applied to nor participated in the program. All students were followed until residency program selection had occurred, after which each participant in the assistantship program completed a questionnaire regarding the effect of the assistantship on residency selection. RESULTS: The difference in rate of family practice residency selection between the participants (n = 31) and those who applied but were not accepted (n = 57) was not significant (X2 = .3, df = 1, P = NS). However, the difference in family practice residency selection between the participants and those not applying (n = 403) was significant (X2 = 6.46, df = 1, P < .05). Participants selecting a family practice residency program were more likely to feel that the summer assistantship experience was their basis for selecting their residencies (mean 7.6 versus 4.7, P < .05 for t test). CONCLUSION: The difference in the rate of entry into family practice residency programs between the assistantship participants and those who applied but were not accepted was not significant. PMID- 8458558 TI - Leadership development for medical students--beyond the prescription pad. AB - BACKGROUND: Physicians are often perceived as leaders in their communities and are expected to participate in politics, business, and volunteer activities. Medical students receive little guidance about becoming effective community leaders. PROGRAM DESCRIPTION: We developed a leadership training program for medical students. Participation in the program was voluntary. The principal forum for this program was a dinner seminar series, which emphasized presentations by current community leaders and identification of leadership opportunities in which medical students could participate. PROGRAM EVALUATION: Information collected at the onset of the program identified the students' concern and priorities regarding leadership activities. Seventy-seven percent of participating students identified good communication skills as the most important quality of a leader. In identifying an issue in which physicians might become involved, students noted only medically related issues, such as access to health care. No long term evaluation data are available to assess the effect of this program. CONCLUSION: Medical school curricula should teach students the leadership skills they will need to participate in community activities. PMID- 8458559 TI - Increasing inter-rater agreement on a family medicine clerkship oral examination- a pilot study. AB - BACKGROUND AND OBJECTIVES: Although oral examinations are a traditional measure of student performance during clinical clerkships, concerns have been expressed about poor inter-rater reliability on these examinations. This study examines inter-rater agreement in a family medicine clerkship oral examination. METHODS: Our study analyzed oral examination scores awarded to a class of 98 junior medical students by three categories of examiner (the clerkship director, full time faculty, and third-year residents). For each student, the difference among the three examiners' raw scores was compared using a Cronbach statistic. Mean scores for the year awarded by each of the three groups of examiners were compared using a correlation coefficient and paired t tests. For students with high inter-rater disagreement, examiner narrative comments and types of questions on which raters disagreed were analyzed. RESULTS: Overall inter-rater agreement was high (Cronbach's alpha = .875). Paired t tests were nonsignificant between residents and faculty but were significant between residents and the clerkship director and between faculty and the clerkship director. In the small subset of students with little inter-rater agreement, no clear trends were identified to explain reasons for evaluator disagreement. CONCLUSION: High levels of inter rater agreement on a clerkship oral examination can occur when several measures to increase inter-rater agreement are used. PMID- 8458560 TI - A comparative view of the Myers-Briggs type indicator. AB - BACKGROUND AND OBJECTIVES: Many family practice residency programs use the Myers Briggs Type Indicator (MBTI) in the process of resident advising. The purpose of this study was to validate the MBTI with an alternative personality evaluation instrument. METHODS: We evaluated 44 residents with both the MBTI and the Sixteen Personality Factor Questionnaire (16PF) and computed correlation coefficients. RESULTS: The highest correlations between the two tests were for the Extraversion/Introversion dimension of personality (r = -.71). The 16PF factors of Tough Poise, Independence, and Superego/Control were also significantly correlated with items on the MBTI. The Anxiety dimension of the 16PF yielded no significant correlations with the MBTI. CONCLUSIONS: The Extraversion/Introversion variables of the MBTI and 16PF are highly correlated. Other variables on the 16PF and MBTI are also correlated. PMID- 8458561 TI - The effect of the APACHE II score and selected clinical variables on survival following cardiopulmonary resuscitation. AB - BACKGROUND AND OBJECTIVES: The purpose of this analysis is to determine the effect of the Acute Physiology and Chronic Health Evaluation (APACHE) II score and other clinical variables on survival following cardiopulmonary resuscitation (CPR) and to identify patient subpopulations with extremely poor survival. METHODS: A retrospective chart review was performed on 218 consecutive adult inpatients undergoing CPR on the general wards and in the intensive care units of a community hospital between January 1, 1989, and July 1, 1991. The patient's age, sex, prior residence, reason for admission, discharge diagnoses, discharge disposition, APACHE II score, and cardiac ejection fraction by echocardiography were recorded. RESULTS: The age, sex, and reason for admission were not significant predictors of survival following CPR. Multiple variable analysis revealed that an increasing APACHE II score (P = .05), a serum creatinine greater than 311 mumol per L (3.5 mg per dL, P = .02), and metastatic cancer (P = .04) were each related to a decreased rate of survival to discharge following CPR. Patient subpopulations with a 0% rate of survival to discharge included those with metastatic cancer (n = 26, P = .02), a serum creatinine greater than 311 mumol per L (3.5 mg per dL) on admission (n = 22, P = .03), and a diagnosis of cardiovascular disease with an APACHE II score greater than 15 on admission (n = 18, P = .007). CONCLUSIONS: The APACHE II score is a useful predictor of failure to survive to discharge following CPR. Several groups of patients were identified with negligible rates of survival to discharge. Physicians should use such prediagnostic information to provide patients with informed consent when discussing do-not-resuscitate (DNR) orders. We suggest that physicians make a special effort to address the DNR status of patients falling to one of the negligible-survival groups identified by this study. PMID- 8458562 TI - Prenatal behavioral risk screening by computer among Native Americans. AB - BACKGROUND AND OBJECTIVES: Computer interviews have potential value in screening pregnant patients for substance abuse and other behavioral risk factors linked to adverse pregnancy outcomes. The focus of this study was to determine whether a patient-interactive computerized assessment and education program was an acceptable and valid means of obtaining behavioral risk data. METHODS: Study participants completed a computer interview, and computer-generated reports of substance use and physical abuse within the past year were compared with information in the participants' prenatal records. The accuracy of computer interview reports of substance use was evaluated by performing urine drug screens. RESULTS: More than 95% of the 265 women who completed the computer interview rated it favorably. Drug use and physical abuse were reported significantly more often during the computer interview, compared with information obtained from the patients' medical records. Results of urine drug screens demonstrated a high concurrence rate between self-reports of drug use and the results of urine analyses. CONCLUSIONS: Results indicated that the computerized assessment was well received by patients and yielded valid information regarding risk factors for adverse pregnancy outcomes. PMID- 8458563 TI - Querying physicians' beliefs in career choice studies: the limitations of introspective causal reports. AB - Numerous studies in family medicine literature explore the determinants of physicians' specialty and practice location choices. A research approach frequently used in these studies has been to ask study physicians what led them to make specific career choices, labeled here as the introspective causal reports study design. This paper explores the validity of introspective causal reports and their usefulness in making health manpower policy recommendations. The accuracy of people's beliefs about the causes of their own behaviors is examined, and social psychology literature is drawn upon in this examination. Data are presented characterizing the use of introspective causal reports in recent family medicine literature. Recommendations are made for stronger research designs in future physician career choice determinant studies. PMID- 8458564 TI - Digestive Disease Week and the 94th annual meeting of the American Gastroenterological Association. Boston, Massachusetts, May 15-21, 1993. Abstracts. PMID- 8458565 TI - Isolation of Lhcb3 sequences from Brassica napus: evidence for conserved genes encoding LHCII type III chlorophyll a/b binding proteins. AB - Three closely related sequences were isolated from Brassica napus genomic DNA and were identified as Lhcb3 (genes encoding type III chlorophyll a/b binding proteins of LHCII, the major light-harvesting complex of photosystem II). These genes, as was observed for a tomato Lhcb3, contain two introns and yield both divergent and conserved predicted amino acid segments as compared with type I and type II polypeptides. One of the B. napus genes, designated Lhcb3*1, is transcribed in vivo, since it is identical to corresponding sequences in a cDNA clone. The protein deduced from another sequence, Lhcb3*2, appears as the most divergent type III so far characterized. The partial sequence of a third gene, Lhcb3*3, was also recovered. The 5' noncoding sequences of Lhcb3*1 and Lhcb3*2, in the far upstream region, are characterized by an extremely high AT content and extensive direct repeats. In the near upstream region, two long Lhcb3*2 segments are very similar to a segment proposed as containing regulatory signals in Lhcb3*1. Specific binding of nuclear proteins to Lhcb3*1 promoter fragments was detected by electrophoretic mobility-shift assays. The evolutionary relationship between genes for type III polypeptides and the other types present in LHCII is discussed. PMID- 8458566 TI - Paraquat selection identifies X-linked oxygen defense genes in Drosophila melanogaster. AB - We have previously shown that homozygous mutants of Drosophila melanogaster deficient in the oxygen radical scavengers, CuZn superoxide dismutase or urate, are adult viable and yet hypersensitive to the oxygen radical-generating agent, paraquat. Thus, paraquat could be used as a selective agent to identify adult viable mutants potentially defective in other, perhaps unknown, oxygen defense functions. Here we report the successful use of paraquat hypersensitivity in the isolation of X-linked, ethylmethanesulfonate-induced mutations affecting oxygen defense in Drosophila melanogaster. Two paraquat hypersensitive mutants were identified that, by complementation analysis, were shown to be new alleles of the maroon-like gene. In addition to paraquat hypersensitivity, both alleles confer a maternally affected dark brown eye color and a complete lack of enzymatically active xanthine dehydrogenase, both of which are characteristic phenotypes of known maroon-like alleles. We conclude that the lack of xanthine dehydrogenase in these mutants leads to the absence of urate, which is the proximate cause of paraquat sensitivity. Because our search for such mutants on the X chromosome revealed two alleles of only a single selectable gene, we anticipate that the total number of major oxygen defense genes in the complete Drosophila genome may not be large. PMID- 8458567 TI - Conservation of a satellite DNA sequence (SATB) in the tilapiine and haplochromine genome (Pisces: Cichlidae). AB - We have cloned and sequenced a 1900-bp EcoRI fragment (SATB) from the tilapiine fish Oreochromis niloticus. The SATB sequence is highly reiterated in the tilapiine genome and organized in long tandem arrays. A 760-bp HindIII fragment, an internal component of SATB, has also been cloned and sequenced from the related tilapiine species Oreochromis hornorum. Hybridization of the radiolabelled 760-bp HindIII repeat detected the presence of the SATB repeat in the genomes of several tilapiine species as well as the haplochromine species Haplochromis (Protomelas) similis. The 760-bp HindIII fragment did not hybridize to genomic DNA of Etroplus maculatus (an Asian cichlid) or to that of Cichlasoma meeki (a South American cichlid). The SATB repeat sequence is 56% AT and constitutes 0.2-5% of the tilapiine genome depending on the species examined. Four imperfect 21-bp direct repeat sequences are present within the cloned 1900 bp EcoRI repeat. Alignment of the four direct repeats from the O. niloticus cloned 1900-bp DNA and the two homologous direct repeats from the O. hornorum 760 bp HindIII repeat revealed a core motif of 11 bp that exhibits 100% sequence identity between all of the direct repeats. The conservation of this motif in the SATB repeat suggests that this sequence may be under selective constraint. PMID- 8458568 TI - Mammalian sex chromosomes. VI. Synapsis in the heterochromatin-rich X chromosomes of four rodent species, Mus dunni, Bandicota bengalensis, Mesocricetus auratus, and Nesokia indica. AB - This study analyzes the progression of chromosomal synapsis in female meiosis of four rodent species, Mus dunni, Bandicota bengalensis, Mesocricetus auratus, and Nesokia indica. Special attention has been paid to understand the mode of pairing between heterochromatin-rich X chromosomes. The ovaries were obtained from newborn individuals instead of fetuses. In all but M. auratus, day 0 ovaries provided almost all the prophase stages at varying frequencies. In B. bengalensis and M. dunni the entire X chromosomes were paired including the heterochromatin. In M. auratus and N. indica, the heterochromatic arms in a proportion of X bivalents, however, were only partially synapsed. It appears that in these two species heterochromatin association is either delayed or short lived. PMID- 8458569 TI - Distribution of TaqI sites along human chromosomes revealed by in situ enzyme nick translation. AB - We have studied the relative richness of TaqI sites along human chromosomes by means of a nonradioactive in situ enzyme-nick translation procedure. Regions with a higher content of these sequences are shown to be the noncentromeric heterochromatin blocks, whereas within euchromatin, terminal R-bands are the domains more enriched in these sites. Results obtained suggest that the method of performing enzyme digestions using time as a variable, and then in situ nick translation, provides much more complete information about the distribution of enzyme sequences along chromosomes than standard enzyme digestions. PMID- 8458570 TI - Sequencing of chromosome I from Saccharomyces cerevisiae: analysis of a 32 kb region between the LTE1 and SPO7 genes. AB - The DNA sequencing and preliminary functional analysis of a 32 kb section of yeast chromosome I has been completed. This region lies on the left arm of the chromosome between the LTE1 and SPO7 genes and contains 14 open reading frames (ORFs) positioned closely together, with an average spacing of approximately 350 nucleotides between coding regions. Three of these ORFs correspond to previously identified genes, a further three show significant homology with other proteins, while the remaining eight ORFs share no significant homology to genes in the databases. PMID- 8458571 TI - Genetic relationships and variation in the Stylosanthes guianensis species complex assessed by random amplified polymorphic DNA. AB - Genetic variation in the five taxonomic groups of the Stylosanthes guianensis (Aubl.) Sw. complex was investigated using random amplified polymorphic DNA markers (RAPDs). DNA samples from four plants of each of 45 accessions within the S. guianensis species complex were analyzed using 20 oligonucleotides of random sequence. Little variation was found within each of the 18 accessions (1-7% of total RAPD bands in pairwise comparisons) and none within each of the other 27 accessions. However, higher levels of polymorphisms were observed both within (index of genetic distance = 1 - F = 0.16-0.248) and between (1 - F = 0.254 0.408) the five taxa. This level of differentiation at the DNA level supported an earlier classification of the taxa as distinct species. A phenogram based on band sharing was constructed to show genetic relationships among the taxa studied. This phenogram corroborated the description of relationships based on morphological-agronomic characteristics, seed protein patterns, rhizobial affinities, crossability, and pollen stainability of the hybrids. In this phenogram, the most similar species were S. grandiflora and S. hippocampoides (1 F = 0.264), with S. acuminata also showing closest similarity to these two species (1 - F = 0.277 and 0.283, respectively). Stylosanthes gracilis accessions showed the closest similarity (1 - F = 0.296) to S. guianensis ssp. guianensis accessions. Lowest similarity values (1 - F = 0.335-0.411) were found between these two species and S. grandiflora, S. acuminata, and S. hippocampoides. PMID- 8458572 TI - Inheritance of random amplified polymorphic DNA markers in an interspecific cross in the genus Stylosanthes. AB - The inheritance of random amplified polymorphic DNA (RAPD) markers generated via the polymerase chain reaction amplification of genomic DNA sequences in an F2 family of an interspecific cross between Stylosanthes hamata and S. scabra was investigated. An initial comparison between the parental species, S. hamata cv. Verano and S. scabra cv. Fitzroy, demonstrated that 34% of detected RAPD bands were polymorphic. Of 90 primers tested, 35 showed relatively simple and reliably scorable polymorphisms and were used for segregation analysis. Sixty F2 individuals were scored for the segregation of 73 RAPD markers and 55 of these markers fit a 3:1 ratio. Segregation of eight other RAPD markers deviated significantly from a 3:1 ratio. There was no bias in the inheritance of RAPD markers regarding parental origin of the segregating RAPD markers. Linkage analysis revealed 10 linkage groups containing a total of 44 RAPD loci. Another 10 RAPD markers (7 of maternal origin) that were polymorphic between the parents did not segregate in the F2 population. One of the maternally inherited RAPD bands hybridized to chloroplast DNA. Analysis of RAPD loci by DNA hybridization indicated that mainly repeated sequences were amplified. These data indicate that RAPDs are useful genetic markers in Stylosanthes spp. and they may be suitable for genetic mapping. PMID- 8458573 TI - Molecular characterization in the dpy-14 region identifies the adenosylhomocysteine hydrolase gene in Caenorhabditis elegans. AB - The region around dpy-14 on chromosome 1 of Caenorhabditis elegans has been extensively studied genetically, with regard to essential gene organization. This region was one of the first for which cloned DNA was available as a result of restriction fragment length polymorphism mapping. To examine the information content of the cloned DNA in this region, evolutionarily conserved sequences were identified by cross-species hybridization. Ten regions of conservation have been identified and characterized with regard to mRNA abundance and DNA sequence. cDNAs were obtained for seven of these conserved regions and sequence from the cDNAs were used to search the SWISS protein and EMBL nucleotide data banks. Two coding regions shared DNA identifies with existing sequences, the opa repeat family of Drosophila and the S-adenosylhomocysteine hydrolase gene. Of the three for which no corresponding cDNA were found, one corresponds to the snRNA U1-1. The other two did not detect transcripts on Northern analysis and are either conserved, but not coding, or code for low abundance transcripts. The density of conserved coding regions in this study was one per 15 kbp of genomic DNA, three times lower than that reported on chromosome 3 by the genome sequencing project. PMID- 8458574 TI - Genetic analysis of the foraging microregion of Drosophila melanogaster. AB - The rover/sitter polymorphism in Drosophila melanogaster larval behaviour is a unique example of a genetically determined, naturally occurring behavioural polymorphism. Allelic variation at the foraging locus (for) accounts for the rover (long foraging paths) and sitter (short foraging paths) phenotypes. We previously developed lethal tagging and used deficiency mapping to place for in the 24A3-C5 interval on the polytene chromosome map, thereby defining the for microregion. Here, we subjected this microregion to mutational analysis to (i) isolate putative lethal foraging mutations and characterize their behavioural phenotypes to assess whether or not for is a vital locus, (ii) generate cytologically detectable chromosome rearrangements with breakpoints in or near for for more precise localization and for future molecular analysis of the for gene, and (iii) identify other gene loci in the immediate vicinity of the for locus. We recovered 10 gamma-induced and 33 ethyl methanesulfonate (EMS) induced new mutations that define seven complementation groups in 24A3-D4. Two new EMS induced lethal for alleles and four gamma-induced rearrangements with breakpoints in for were identified, which allowed us to further localize for to 24A3-5. All lethal mutations in for resulted in an altered behavioural phenotype providing evidence that both vital and behavioural functions are encoded by for. PMID- 8458575 TI - The yeast SNF2/SWI2 protein has DNA-stimulated ATPase activity required for transcriptional activation. AB - The yeast SNF2 (SWI2) protein functions with SNF5, SNF6, SWI1, and SWI3 in the transcriptional activation of many differently regulated genes. These proteins appear to facilitate activation by gene-specific regulatory proteins. SNF2 is highly conserved among eukaryotes and defines a family of proteins with similarity to helicases and nucleic acid-dependent NTPases. Here, we present genetic and biochemical evidence that SNF2 has DNA-stimulated ATPase activity. Mutations in the nucleoside triphosphate (NTP)-binding motif and other conserved motifs impair SNF2 function. Swapping experiments with another member of this family indicate that the helicase-related domains are functionally interchangeable. Finally, bacterially expressed SNF2 protein has ATPase activity that is stimulated by double-stranded DNA, and mutation of the NTP-binding site abolishes this activity. Deletion analysis shows that the helicase-like region of SNF2 is necessary, but not sufficient, for transcriptional activation. PMID- 8458576 TI - Transcriptional silencing in yeast is associated with reduced nucleosome acetylation. AB - Two classes of sequences in the yeast Saccharomyces cerevisiae are subject to transcriptional silencing: the silent mating-type cassettes and telomeres. In this report we demonstrate that the silencing of these regions is strictly associated with acetylation of the epsilon-amino groups of lysines in the amino terminal domains of three of the four core histones. Both the silent mating-type cassettes and the Y domains of telomeres are packaged in nucleosomes in vivo that are hypoacetylated relative to those packaging active genes. This difference in acetylation is eliminated by genetic inactivation of silencing: The silent cassettes from sir2, sir3, or sir4 cells show the same level of acetylation as other active genes. The correspondence of silencing and hypoacetylation of the mating-type cassettes is observed even for an allele lacking a promoter, indicating that silencing per se, rather than the absence of transcription, is correlated with hypoacetylation. Finally, overexpression of Sir2p, a protein required for transcriptional silencing in yeast, yields substantial histone deacetylation in vivo. These studies fortify the hypothesis that silencing in yeast results from heterochromatin formation and argue that the silencing proteins participate in this formation. PMID- 8458577 TI - Sister chromatid fusion initiates amplification of the dihydrofolate reductase gene in Chinese hamster cells. AB - We have utilized a dihydrofolate reductase (DHFR) probe in combination with selected probes from other positions along the 2q chromosome arm in a two-color fluorescence in situ hybridization analysis of early DHFR gene amplification events in CHO cells. These studies show clearly that the most frequent initiating event is the formation of a giant inverted duplication, resulting from chromosome breakage and terminal fusion or a reverse unequal sister chromatid exchange. The dicentric chromosomes thus formed initiate bridge/breakage/fusion cycles that appear to mediate subsequent amplification steps to higher copy number. PMID- 8458578 TI - Control of cell fate determination by p21ras/Ras1, an essential component of torso signaling in Drosophila. AB - Determination of cell fate at the posterior termini of the Drosophila embryo is specified by the activation of the torso (tor) receptor tyrosine kinase. This signaling pathway is mediated by the serine/threonine kinase D-raf and a protein tyrosine phosphatase corkscrew (csw). We found that expression of an activated form of Ras1 during oogenesis resulted in embryos with tor gain-of-function phenotypes. To demonstrate that p21ras/Ras1 mediates tor signaling, we injected mammalian p21ras variants into early Drosophila embryos. We found that the injection of activated p21v-ras rescued the maternal-effect phenotypes of both tor and csw null mutations. These rescuing effects of p21v-ras are dependent on the presence of maternally derived D-raf activity. In addition, wild-type embryos show a terminal-class phenotype resembling csw when injected with p21rasN17, a dominant-negative form of p21ras. Furthermore, we have analyzed the maternal effect phenotype of Son of sevenless (Sos), a positive regulator of Ras1, and showed that embryos derived from germ cells lacking Sos+ activity exhibit a terminal-class phenotype. Our study demonstrates that the Drosophila p21ras, encoded by Ras1, is an intrinsic component of the tor signaling pathway, where it is both necessary and sufficient in specifying posterior terminal cell fates. p21ras/Ras1 operates upstream of the D-raf kinase in this signaling pathway. PMID- 8458579 TI - A null c-myc mutation causes lethality before 10.5 days of gestation in homozygotes and reduced fertility in heterozygous female mice. AB - To directly assess c-myc function in cellular proliferation, differentiation, and embryogenesis, we have used homologous recombination in embryonic stem cells to generate both heterozygous and homozygous c-myc mutant ES cell lines. The mutation is a null allele at the protein level. Mouse chimeras from seven heterozygous cell lines transmitted the mutant allele to their offspring. The analysis of embryos from two clones has shown that the mutation is lethal in homozygotes between 9.5 and 10.5 days of gestation. The embryos are generally smaller and retarded in development compared with their littermates. Pathologic abnormalities include the heart, pericardium, neural tube, and delay or failure in turning of the embryo. Heterozygous females have reduced fertility owing to embryonic resorption before 9.5 days of gestation in 14% of implanted embryos. c Myc protein is necessary for embryonic survival beyond 10.5 days of gestation; however, it appears to be dispensable for cell division both in ES cell lines and in the embryo before that time. PMID- 8458580 TI - The interplay between multiple enhancer and silencer elements defines the pattern of decapentaplegic expression. AB - The product of the zygotically active decapentaplegic (dpp) gene appears to function as a morphogen that specifies positional information in the dorsal half of the Drosophila embryo. The dorsal-specific transcription of dpp is the key step in establishing a morphogen gradient. We demonstrate here that multiple regions within the second intron of the gene cooperate with one another to generate the wild-type level and pattern of dpp transcription. These regions contain both generalized enhancer elements as well as ventral-specific repressor elements. Placed within the context of heterologous promoters, the intron retains its ability to direct general activation and ventral repression. The ventral specific repression of dpp transcription is directly mediated by binding sites for the dorsal (dl) morphogen in the repressor elements. In contrast with the zerknullt (zen) ventral repressor element, which contains a few high-affinity dl binding sites, dpp contains multiple relatively low-affinity sites that function together to bring about complete ventral repression. Because dpp and zen have nearly coincident early expression domains, these results indicate that the same boundary of repression can be specified by dl-binding sites of different affinity. We discuss the possibility that unknown factors interact with dl protein to determine the domain of dl-mediated repression. PMID- 8458581 TI - p105 and p98 precursor proteins play an active role in NF-kappa B-mediated signal transduction. AB - The Rel/NF-kappa B family of transcription factors is composed of two distinct subgroups, proteins that undergo proteolytic processing and contain SWI6/ankyrin repeats in their carboxyl termini (p105, p98), and those without such repeats that do not require processing (p65, c-Rel, RelB, and Dorsal). We demonstrate that the p105 and p98 precursors share functional properties with the I kappa B proteins, which also contain SWI6/ankyrin repeats. Both p105 and p98 were found to form stable complexes with other Rel/NF-kappa B family members, including p65 and c-Rel. Association with the precursors is sufficient for cytoplasmic retention of either p65 or c-Rel, both of which are otherwise nuclear. These complexes undergo stimulus-responsive processing to produce active p50/c-Rel and p55/c-Rel complexes. These observations suggest a second pathway leading to NF kappa B induction, in which processing of the precursors rather than phosphorylation of I kappa B plays a major role. PMID- 8458582 TI - Distribution of spin-trapping compounds in rat blood and brain: in vivo microdialysis determination. AB - Microdialysis was utilized to determine blood and brain distribution of spin trapping nitrone compounds in the rat following intraperitoneal administration. In vivo quantitation by high-pressure liquid chromatography (HPLC) analysis, in vitro calibration of microdialysis probes, optimum perfusion rate, and the relationship of microdialysis sample recovery to tissue levels were evaluated in detail. The microdialysis sampling and HPLC analysis provided on-line, within animal pharmacokinetic time-course determinations. At equimolar concentrations, 150 mg/kg alpha-phenyl-N-tert-butyl nitrone (PBN) or 165 mg/kg alpha-4-pyridyl-N oxide N-tert-butyl nitrone (POBN) reached a similar, steady-state venous blood concentration of 224 +/- 21 microM and 210 +/- 10 microM, respectively. The POBN steady-state brain concentration was 149 +/- 9 microM, a significantly (p < .05) lower concentration than in the blood. In contrast, the brain concentration of PBN was 331 +/- 25 microM, significantly (p < .05) higher than its concentration in the blood. The increased brain distribution/penetration of PBN was attributed to its greater lipophilicity as measured by its octanol/water partition coefficient. All microdialysis results were validated by direct measurement of blood and brain levels at steady-state using conventional extraction procedures and assays. Also, the amount of tissue/cell bound versus unbound nitrones was determined by comparing the microdialysis "dialyzable" fraction with the total amount from whole tissue extracts. These data demonstrate that on-line determinations of nitrone spin-trap brain penetration/levels can be carried out accurately using in vivo microdialysis. The implication of these results for potential use of the microdialysis technique for detection of free radical products in in vivo animal models is discussed. PMID- 8458583 TI - Selenoperoxidase-mediated cytoprotection against the damaging effects of tert butyl hydroperoxide on leukemia cells. AB - Murine leukemia L1210 cells grown for 5-7 d in the presence of 1% serum without added selenium [Se(-) cells] expressed < 5% of the glutathione peroxidase (GPX) activity of selenium-supplemented controls [Se(+) cells]. Clonogenic survival assays indicated that t-butyl hydroperoxide (t-BuOOH) is much more toxic to Se(-) cells (LC50 approximately 10 microM) than to Se(+) or selenium-repleted [Se(-/+)] cells (LC50 approximately 250 microM). Hypersensitivity of Se(-) cells to t-BuOOH was partially reversed by treating them with Ebselen, a selenoperoxidase mimetic; thus, selenoperoxidase insufficiency was probably the most serious defect of Se deprivation. Cytotoxicity of t-BuOOH was inhibited by desferrioxamine and by alpha-tocopherol, indicating that redox iron and free radical intermediates are involved. Elevated sensitivity of Se(-) cells to t-BuOOH was accompanied by an increased susceptibility to free radical lipid peroxidation, which became even more pronounced in cells that had been grown in arachidonate (20:4, n-6) supplemented media. That glutathione (GSH) is required for cytoprotection was established by showing that Se(+) cells are less resistant to t-BuOOH after exposure to buthionine sulfoximine (BSO), an inhibitor of GSH synthesis, or 1,3 bis(2-chloroethyl)-1-nitrosourea (BCNU), an inhibitor of glutathione reductase. Coupled enzymatic assays indicated that Se(+) or Se(-/+) cells metabolize t-BuOOH 20-25 times more rapidly than Se(-), consistent with the measured difference in GPX activities of these cells. Correspondingly, when challenged with t-BuOOH, Se(+) cells showed an initial loss of GSH and elevation of GSSG that exceeded that of Se(-) cells. It was further shown that like Se(-) cells, BSO- or BCNU treated Se(+) cells metabolize t-BuOOH more slowly than nontreated controls. These results clearly indicate that selenoperoxidase action in the glutathione cycle is a vital element in cellular defense against toxic hydroperoxides. PMID- 8458584 TI - Hyperoxia induces DNA damage in mammalian cells. AB - There is mounting evidence on the role of oxygen-derived free radicals in causing damage to various cellular components. However, most studies reported in the literature have been conducted under conditions where cells were challenged with chemical free radical generating systems. In contrast, we measured DNA strand breaks, through a relatively simple and sensitive technique, as a function of the dissolved oxygen tension in a bioreactor. Cells were exposed to a step change in oxygen tension at mid-exponential growth phase. Several levels of oxygen were tested (200, 300, and 476% dissolved oxygen with respect to air saturation at 1 atmosphere) and compared against a control (10% dissolved oxygen). Hyperoxia was found to cause monotonically increasing DNA strand breakage at all the oxygen levels. In addition, hyperoxia was found to affect other metabolic functions such as the glucose consumption rate, lactate production rate, and cell growth. When hyperoxia-induced DNA strand breakage was compared to that induced by exposure to hydrogen peroxide, a similar response was observed. Exposure to a dissolved oxygen level of 200% induced DNA strand breakage comparable to a bolus of 4.2 microM hydrogen peroxide. Our results show that there is an association between hyperoxia and DNA damage. PMID- 8458585 TI - Effects of the spin trap alpha-phenyl N-tert-butyl nitrone on myocardial function and flow: a dose-response study in the open-chest dog and in the isolated rat heart. AB - Alpha-phenyl N-tert-butyl nitrone (PBN) is widely used in spin-trapping experiments, but its possible toxicity has not been systematically evaluated. The purpose of this study was to investigate the effects of different doses of PBN on cardiac function in vivo (open-chest dogs) and in vitro (isolated rat hearts). In open-chest dogs, PBN was infused intracoronarily to achieve coronary arterial concentrations ranging from 1.6 mM to 10.0 mM. At coronary arterial concentrations of 1.6 mM and 2.5 mM, PBN had no appreciable effect on regional myocardial function (assessed as systolic wall thickening). However, coronary arterial concentrations of PBN of 5.0 mM and 10.0 mM produced a marked reduction and, eventually, a complete loss of systolic wall thickening (53% of baseline values after 30 min at 5.0 mM and 14% after 30 min at 10.0 mM). Furthermore, PBN increased coronary blood flow by approximately 25% at 2.5 mM and by > 100% at 10.0 mM. In isolated rat hearts, perfusion with 2.5 and 5.0 mM PBN for 60 min did not significantly affect global myocardial function, assessed as developed pressure, rate-pressure product, and positive and negative dP/dt. At the 10.0 mM concentration, however, these variables were significantly decreased after 30 min (developed pressure: -77% vs. controls; rate-pressure product: -84%; +dP/dt: 60%; -dP/dt: -70%); two out of five hearts stopped beating within 30 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458586 TI - Reactive oxygen species associated with cell differentiation in Neurospora crassa. AB - The conidiation process of Neurospora crassa is characterized by three morphogenetic events: adhesion of hyphae, development of aerial hyphae, and conidia formation. At the onset of all three events a spontaneous, low-level chemiluminescence was detected, indicating the formation of reactive oxygen species. Hyperoxic conditions increased chemiluminescence and accelerated differentiation. Hypoxic conditions abolished both chemiluminescence and differentiation. Chemiluminescence was enhanced by lucigenin and/or luminol. Butylated hydroxytoluene and antioxidants that do not readily enter the cells, like superoxide dismutase and catalase, did not lower the chemiluminescence nor had they an inhibitory effect on the differentiation process. In contrast, N,N'diphenyl-1,4-phenylene diamide, 1,3-dimethyl-2-thiourea, ammonium pyrrolinedimethyl-dithiocarbamate, and N-acetyl-L-cysteine retarded the onset or abolished both the chemiluminescence and the differentiation process. These results further support our hypothesis (Hansberg, W.; Aguirre, J. J. Theor. Biol. 142:201-221; 1990) that a hyperoxidant state triggers cell differentiation events. PMID- 8458587 TI - Decreased endothelium-dependent vascular relaxation following subtotal coronary artery occlusion in dogs. AB - Total coronary artery occlusion followed by reperfusion leads to neutrophil accumulation in the reperfused myocardium and a reduction in endothelium dependent coronary artery relaxation. Attenuated coronary artery relaxation in the affected regions is thought to be related to breakdown of endothelium-derived relaxing factor (EDRF) by free oxygen radicals released during reperfusion. To determine if temporary subtotal coronary artery narrowing leads to similar alteration in vascular reactivity, eight open-chest dogs were subjected to 1 h of left anterior descending (LAD) coronary artery narrowing (70% reduction in basal flow) and pacing-induced increase in heart rate (30% above baseline) followed by reperfusion for 1 h. Thereafter reactivity of ischemic-reperfused LAD and nonischemic circumflex (Cx) coronary artery rings to the thromboxane A2 analog U46,619 and EDRF-dependent vasorelaxants acetylcholine (ACh), thrombin, and adenosine diphosphate (ADP), as well as to EDRF-independent vasorelaxant nitroglycerin (NTG), was examined. Unlike in the setting of total coronary artery occlusion, reperfused myocardium or LAD did not reveal neutrophil infiltration. However, contraction in response to U46,619 was markedly (P < .001) increased in the LAD rings compared to that in the Cx rings. ACh-induced relaxation was only modestly decreased (P < .05) in the LAD coronary artery rings, but the relaxation in response to both thrombin and ADP was markedly diminished (P < .01) as compared to that in the Cx rings. Coronary artery ring relaxation in response to NTG was preserved in the LAD rings. Pretreatment of coronary artery rings with indomethacin did not alter the enhanced contraction or diminished endothelium dependent relaxation of LAD coronary artery rings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458588 TI - Oxygen-radical absorbance capacity assay for antioxidants. AB - A relatively simple but sensitive and reliable method of quantitating the oxygen radical absorbing capacity (ORAC) of antioxidants in serum using a few microliter is described. In this assay system, beta-phycoerythrin (beta-PE) is used as an indicator protein, 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) as a peroxyl radical generator, and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox, a water-soluble vitamin E analogue) as a control standard. Results are expressed as ORAC units, where 1 ORAC unit equals the net protection produced by 1 microM Trolox. The uniqueness of this assay is that total antioxidant capacity of a sample is estimated by taking the oxidation reaction to completion. At this point all of the nonprotein antioxidants (which include alpha-tocopherol, vitamin C, beta-carotene, uric acid, and bilirubin) and most of the albumin in the sample are oxidized by the peroxyl radical. Results are quantified by measuring the protection produced by antioxidants. This solves many problems associated with kinetics or lag-time measurements. A linear correlation of ORAC value with concentration of serum. Trolox, vitamin C, uric acid, and bovine albumin is demonstrated. The coefficient of variation within a run is found to be about 2% and from run to run about 5%. Trolox, alpha-tocopherol, vitamin C, beta carotene, uric acid, and bilirubin completely protect beta-PE from oxidation, while bovine albumin protects beta-PE only partially. On a molar basis, the relative peroxyl radical absorbance capacity of Trolox, alpha-tocopherol acid succinate, uric acid, bilirubin, and vitamin C is 1:1:0.92:0.84:0.52. Bovine albumin per unit weight has a lower peroxyl absorbing capacity than these antioxidants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458589 TI - Ebselen, a selenoorganic compound as glutathione peroxidase mimic. AB - The selenoorganic compound ebselen, 2-phenyl-1,2-benzisoselenazol-3(2H)-one, exhibits activity as an enzyme mimic. The reaction catalyzed is that of a glutathione (GSH) peroxidase (i.e., the reduction of a hydroperoxide at the expense of thiol). The specificity for substrates ranges from hydrogen peroxide and smaller organic hydroperoxides to membrane-bound phospholipid and cholesterol hydroperoxides. In addition to glutathione, the thiol reductant cosubstrate can be dithioerythritol, N-acetylcysteine or dihydrolipoate, or other suitable thiol compounds. Ebselen also has properties such as free radical and singlet oxygen quenching. Model experiments in vitro with liposomes, microsomes, isolated cells, and organs show that the protection against oxidative challenge afforded by ebselen can be explained largely by the activity as GSH peroxidase mimic. Whether this also explains the known preliminary results in clinical settings is yet open. The metabolism and disposition of ebselen is presented in this review. The main point is that the selenium is not bioavailable, explaining the extremely low toxicity observed in animal studies. The occurrence of natural GPx mimics, ovothiol and related compounds, is briefly mentioned. PMID- 8458590 TI - Oxygen free radicals and metallothionein. AB - It is generally accepted that the principal roles of metallothionein lie in the detoxification of heavy metals and regulation of the metabolism of essential trace metals. However, there is increasing evidence that it can act as a free radical scavenger. This article reviews the evidence supporting such a physiological role and describes induction of metallothionein synthesis by oxidative stress, possible mediators for this induction, and the radical scavenging capability of metallothionein in tissues and cells. The relationship between metallothionein and other antioxidant defense systems and the medical implications of the free radical scavenging properties of metallothionein are also discussed. PMID- 8458591 TI - Inability of dimethylthiourea to limit tissue necrosis during acute myocardial infarction. PMID- 8458593 TI - My experience as a courier. PMID- 8458592 TI - An FNS fantasy. PMID- 8458594 TI - [MRSA infection]. PMID- 8458595 TI - [Analysis of molecular mechanism in colorectal tumorigenesis]. AB - Genetic alterations of Ki-ras gene, p53 gene, and DCC gene were analyzed in human colon cancer cell lines (HCCLs). On the basis of these analyses, a HCCL (HCT116) human chromosome 18 hybrids, and targeted cell lines that were disrupted at the activated Ki-ras gene in HCCLs (HCT116 and DLD-1), were established. Tumorigenicity and expression of c-myc gene were investigated in these cell lines, respectively. 1. Point mutations of Ki-ras gene, p53 gene, and insertion mutations of DCC gene were detected in 10 out of 18 HCCLs, 8 out of 15 HCCLs, and 3 out of 16 HCCLs, respectively. 2. HCT116-chromosome 18 hybrids were morphologically similar to the parental line, and were not suppressed for tumorigenicity in vitro, but they produced slowly growing tumors in nude mice compared with the growth of the parental line. 3. The targeted cell lines that were disrupted at the activated Ki-ras gene were morphologically altered and lost neoplastic phenotypes, including tumorigenicity in nude mice and anchorage independent growth. Furthermore, expression of c-myc gene in these clones was much reduced compared with findings in the parental line, regardless of their growth rates. PMID- 8458596 TI - Clinical application of phosphoenolpyruvate (PEP) to autologous transfusion of patients with open heart surgery. AB - Patients undergoing surgery for cardiac valve replacement were autologously transfused after their cryopreserved blood was treated with phosphoenolpyruvate. Five patients received red cells treated on the day of operation with a solution containing phosphoenolpyruvate, the other 6 serving as a control group. None of the patients received homologous blood. The treated red cells had a normal adenosine triphosphate concentration; in the control group a 10% decrease was noted. The 2,3-bisphosphoglycerate concentration was 211% of normal in red cells of the treated group and 69% of normal in the control group. The P50 values (mmHg) were 31.1 +/- 3.5 (treated), 20.3 +/- 1.7 (untreated), and 26.1 +/- 0.6 (fresh, not cryopreserved), respectively. Both the 2,3-bisphosphoglycerate and P50 values of the circulating blood were significantly (p < 0.02) increased in the patients receiving treated red cells. The increase in the 2,3 bisphosphoglycerate and P50 remained for 6 hours after transfusion at which time the levels of the 2,3-bisphosphoglycerate were 14.5 +/- 2.2 mumol/gHb (treated group) and 10.5 +/- 0.8 mumol/gHb (control group). Those of P50 were 28.1 +/- 1.5 mmHg (treated group) and 25.9 +/- 0.9 mmHg (control group). The adenosine triphosphate levels were not significantly different. The postoperative values of pH and hematocrit did not differ between the two groups. It was estimated that the oxygen delivery capacity in the circulating blood was about 30% higher in the patients receiving phosphoenolpyruvate treated blood than in those receiving untreated blood. PMID- 8458597 TI - Pharmacokinetics and pharmacodynamics of zolpidem following repeated doses in hemodialyzed uraemic patients. AB - Zolpidem, an imidazopyridine derivative, is a chemically novel, non benzodiazepine hypnotic agent. Many uraemic patients complain of sleep disorders and ask for hypnotic medication which is well tolerated both clinically and biologically in such patients. We studied the pharmacokinetics and pharmacodynamics of zolpidem in 12 end-stage renal patients regularly treated by hemodialysis three times a week. Zolpidem (10 mg) was given orally for 14 or 21 days. Pharmacokinetic and pharmacodynamic evaluations were repeated at the end of the study on day 14 or day 21. Cmax, Tmax, t1/2 and the area under the curve were not modified in hemodialyzed patients. After daytime dosing, zolpidem induced the same level of sleepiness after the first and last dose and was well tolerated as a hypnotic agent after the night-time dosing. From these results, it can be said that zolpidem may be administered safely to patients with severe renal impairment without any modification of the dosage regimen. PMID- 8458598 TI - Renal dopamine excretion in healthy volunteers after oral ingestion of L-dopa. AB - L-Dopa is converted to dopamine by aromatic-L-amino acid decarboxylase (AADC). In the kidney, proximal tubular epithelial cells are rich in AADC and urinary free dopamine excretion is a marker for endorenal extraneuronal dopamine synthesis. The urinary free dopamine excretion was analysed in a double-blind cross-over study after oral ingestion of L-Dopa or a placebo in five healthy volunteers. The drug ingestions were separated by one week's wash-out. Since in a preliminary study, two volunteers ingesting a single L-Dopa dose of 500 mg with breakfast experienced nausea, the five volunteers of the present study were given 300 mg L Dopa (50 mg at 9 am with breakfast, 100 mg before lunch and 150 mg before dinner) without any adverse effects. L-Dopa induced an increase in 24-h urinary dopamine excretion (HPLC with electrochemical detection). Free urinary dopamine (1900 micrograms/24 h) accounted for 0.8% of the daily oral L-Dopa dose and represented 10% of total urinary dopamine excretion. L-Dopa treatment had no significant effect on mean ambulatory arterial blood pressure and heart rate measured from 9 am to 6 pm (Spacelabs) or on 24 h urinary water and sodium excretion. PMID- 8458599 TI - K+ channels and control of ventricular repolarization in the heart. AB - K+ channels form a large family, in which voltage-operated and ligand-operated channels can be distinguished. Under physiological conditions, four K+ currents contribute to the repolarization process and their role is discussed: i) the transient outward current (ito) is responsible for the rapid initial repolarization process from the crest of the action potential to the plateau level; ii) the delayed K+ current (iK) is involved in the overall repolarization process during the plateau; iii) the inward rectifier (iK1) is responsible for the final rapid repolarization and the maintenance of the resting potential; iv) a ligand-operated channel activated by acetylcholine and adenosine participates in the repolarization process and the maintenance of the resting potential in nodal, atrial and Purkinje cells. In the context of antiarrhythmic interventions, block of outward K+ current and prolongation of refractoriness is currently considered as an alternative to block of the Na+ current and reduction of conduction velocity. Although some of these drugs show use-dependent block, the frequency-dependent changes in current and action potential duration are not ideal. PMID- 8458600 TI - Experimental models of torsades de pointes. AB - Torsades de pointes is the most typical ventricular tachycardia involving QT interval prolongation. It is a rather unusual but potentially lethal ventricular tachycardia with a distinctive morphology favored by bradycardia, antiarrhythmic drugs and hypokalemia and requires specific treatment. Torsades de pointes has been shown to be related to bradycardia-dependent early afterdepolarizations (EAD) and/or increased dispersion of repolarization. However, although EAD can be obtained relatively easily in vitro with quinidine or sotalol, torsades de pointes are very difficult to reproduce in animal models. The models of torsades de pointes which have been proposed can be categorized as morphological, EAD related or pharmacological models. The purpose of the 'morphological' models was to reproduce the twisting of QRS axis typical of torsades de pointes, with no consideration of other aspects such as long QT or bradycardia. These models were produced by epicardial electrical or chemical (aconitine) stimulation at two distant ventricular sites or by overdosing of quinidine in dogs with acute myocardial infarction. The second type of model focused on the conditions producing EAD in vitro. Ventricular tachycardias were obtained in anesthetized dogs using toxics such as cesium or anthopleurine, both producing EAD in vitro. These ventricular tachycardias were shown to be sensitive to magnesium, heart rate and autonomic tone, but torsades de pointes remained rare, at least after cesium injections. The pharmacological models that could be used to study the QT dependent proarrhythmic effects of drugs are the anesthetized rabbit with alpha adrenergic stimulation, and the conscious dog model with chronic AV-block and diuretic-induced hypokalemia. Methoxamine-treated anesthetized rabbits develop ventricular tachycardias during clofilium infusions. These ventricular tachycardias, although appearing at very high heart rates, have typical torsades de pointes aspects and are often associated with giant QT waves. The specificity of the model remains to be tested. In our conscious bradycardic and hypokalemic dogs, quinidine and sotalol but not flecainide, propranolol or lidocaine induced QT-dependent arrhythmogenic effects and torsades de pointes. Efficacy of high rate stimulations and magnesium were repeatedly observed. This demanding model, especially designed for qualitative drug comparisons, is also well suited to studies on the mechanisms of initiation of torsades de pointes. The pertinence of these models for estimating the risk of QT-dependent proarrhythmias associated with non-antiarrhythmic agents remains to be tested. PMID- 8458601 TI - Early after/depolarizations and triggered activity: mechanisms and autonomic regulation. AB - An early after/depolarization (EAD) is an abnormality of the repolarization process of an action potential which causes an interruption or a retardation of normal repolarization. Two types were described: phase 3 EADs occur at a takeoff potential of approximately-60 mV and phase 2 EADs occur at the end of a prolonged plateau at a takeoff potential of between-10 and-30 mV. EADs can result from an increase in inward current, a reduction of outward current or both. EADs show cycle-length dependence: as cycle length increases and repolarization lengthens, EADs occur, and their magnitude increases, at a critical cycle length, can trigger the action potential of these EADs. The autonomic nervous system can also modulate EADs and trigger activity. In cesium-intoxicated Purkinje fibers, beta adrenergic stimulation increases EAD magnitude and the occurrence of triggered activity. Cholinergic stimulation decreases EAD magnitude and suppresses triggered activity occurring after beta-adrenergic stimulation. Alpha 1 adrenergic stimulation has no effect on phase 3 EADs but induces phase 2 EADs. In normal Tyrode's solution (0 cesium), phenylephrine prolongs action potential and induces EADs. This effect seems to depend on alpha 1 A stimulation. These electrogenic abnormalities are supposed to be responsible for long QT and torsades de pointes. As our experimental data have shown that both the rate of stimulation and the autonomic nervous system could modulate EADs and trigger activity, we can speculate on the therapeutic implications of such modulations and the role of pacing as well as alpha- and beta-adrenergic antagonists. PMID- 8458602 TI - Rate-dependence of class III actions in the heart. AB - The pharmacodynamics of many antiarrhythmic drugs are altered by heart rate. The ability of sodium channel blockers to decrease conduction velocity (class I action) is more pronounced with rapid heart rates. Drugs with class III action increase action potential duration and refractoriness in the heart. Most drugs with class III actions, currently being developed, produce their action by blocking one or several of the potassium channels responsible for repolarization. In vitro and in vivo studies have shown that their ability to increase repolarization time is less pronounced, or even disappears, at rapid pacing or heart rates. This so called 'inverse' rate-dependence of class III action is a characteristic of all drugs currently used in man except amiodarone, for which prolongation of repolarization time persists to a limited extent with rapid heart rates. It has been suggested that one possible mechanism of the inverse rate dependence of class III action is related to the preferential binding of drugs to the potassium channels in the closed, polarized state. An inverse rate-dependence of class III action has also been found on prolongation of refractoriness. However, preliminary studies suggest that the positive inotropism of class III drugs not only persists but may increase with rapid heart rates. The clinical consequences of this phenomenon remain unclear, especially in view of the fact that the rate-dependence of class III action on dispersion of repolarization has not been specifically studied and that class III actions tend to decrease in ischemic tissues. However, the increase of action prolongation at slow heart rates may contribute to the bradycardia-dependent development of torsades de pointes arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458603 TI - Evaluation of drug-induced QT interval modifications in dynamic electrocardiography: the case of bepridil. AB - Drug-induced modifications of QT interval are usually assessed through formulae defining the corrected QT interval "QTc". They are all based on the assumption that the correction is adequate, and that drug-induced heart rate variations and rate-dependent QT changes are proportional. Holter ECG allows to study the repolarization in selected RR cycles while controlling environmental rate-related and circadian influences. Repolarization duration was evaluated in 15 normal individuals and 13 patients with stable coronary artery disease and no heart failure who did not differ in terms of 24-hour heart rate, age and sex. The effects of a 3-month treatment with bepridil were assessed in the latter. Using the conventional evaluation through the corrected QT (Bazett formula), no difference was found between the two groups at baseline, and bepridil induced a non-significant 5% prolongation of QTc. At Holter recordings, the QTa (Q-T apex) duration was linearly correlated with the heart rate over 24 hours. To specifically study day-to-night variations and to exclude the rate-dependent and short-term autonomic influences. QTa was studied in populations of averaged QRS-T selected according to i) the last RR cycle length and ii) an identical mean RR interval during the preceding minute. Both RR values were fixed at 800 ms to obtain the "QTa-800" measured directly or extrapolated from linearly correlated, other RR values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458604 TI - The effect of glycemic control on plasma prealbumin levels in type-1 diabetic children. AB - Plasma prealbumin levels have been used as a sensitive biochemical index in the assessment of nutritional status. The present study was undertaken to determine if diabetic children with uncontrolled diabetes are at greater nutritional risk than those with controlled glycemia. Plasma prealbumin was determined using a radial immunoassay in 42 diabetics and 20 age-matched normal volunteers. Results (mean +/- SE) show that prealbumin levels are significantly (p < 0.02) lower in diabetics (21.5 +/- 1.0) than in normals (25.8 +/- 1.3). Compared with normals, prealbumin levels in controlled diabetics are similar; whereas uncontrolled diabetics have significantly lower (p < 0.05) prealbumin levels. Prealbumin levels were 20.4 +/- 1.7 in uncontrolled diabetics (GHb > 9.00), 21.8 +/- 2.3 in intermediately controlled diabetics (GHb 7.0-9.0), and 22.2 +/- 1.5 in controlled diabetics (GHb < 7.0). The data suggest that diabetics in good control are nutritionally similar to the normal population and that patients in poor control have significantly lower prealbumin than the normal population indicating that metabolic derangement may result in malnutrition. PMID- 8458605 TI - Long-term treatment of central precocious puberty with a long-acting analogue of luteinizing hormone release hormone (D-Tryp6-GnRH) in monthly injections. Its possible use in normal puberty. AB - The gonadotropin-releasing-hormone-like agonist D-Tryp6-GnRH (GnRHa) has been shown to induce reversible suppression of gonadotropins and gonadal steroids in patients with central precocious puberty. We examined the effect of a long-acting preparation of GnRHa in biodegradable microcapsules. D-Tryptophane6-GnRH, administered intramuscularly at 1 month intervals, for 12 consecutive months, on growth and skeletal maturation in 3 girls and 4 boys with neurogenic or idiopathic precocious puberty. Suppression of gonadotropin release after GnRH stimulation and gonadal steroids was maintained in all subjects. Growth velocity fell from a mean rate (+/- SEM) or 8.60 +/- 0.75 cm/year before treatment to 5.81 +/- 0.60 cm/year (p < 0.005) after 1 year. Bone age advanced a mean of 8.0 +/- 0.45 months during treatment, suggesting an increase in predicted height from the ratio delta bone age/delta chronological age. Two subjects, one of them with compensated Bartter's syndrome with normal hypothalamic pituitary-gonadal-axis, received the analogue to delay pubertal growth with the hope to improve final height. In the first one, the growth velocity fell from 9.9 cm/year to 8 cm/year and delta bone age/delta chronological age decreased from 1.28 to 1.0 and in the other subject, the growth velocity fell from 12 cm/year to 6.0 cm/year in the last year of treatment and delta bone age/delta chronological age fell from 3.2 to 0.75, indicating an improvement in predicted height. PMID- 8458606 TI - Acute effects of oral glucose loading on the renin-angiotensin-aldosterone system in patients with chronic renal disease. AB - To determine the changes of the glucose-induced renin-angiotensin-aldosterone system in chronic renal disease, a standard oral glucose loading test (75g) was performed in patients with chronic glomerulonephritis (CGN) (n = 12) and compared with control subjects (10). Glucose loading resulted in a significant decrease of serum aldosterone as well as increases of blood glucose and insulin similarly in both CGN and C. However, the suppression of aldosterone was statistically milder in CGN than in C (p < 0.05). In contrast, significant elevations of plasma renin activity were observed in CGN at 60 and 120 min, but not in C after glucose loading. Urinary sodium excretion after glucose ingestion was lower in CGN than in C. These data demonstrated that the glucose-induced renin-angiotensin aldosterone system in patients with chronic renal disease differed from that in healthy subjects. PMID- 8458607 TI - Urinary free cortisol in the assessment of hydrocortisone replacement therapy. AB - Glucocorticoid replacement therapy should be tailored to individual patients' requirements to avoid the risks of over and under treatment. Serum and urinary free cortisol profiles over 24 hours were compared as a means of assessing replacement therapy in nine patients on long-term twice daily hydrocortisone. Both indices varied in relationship to the timing and dose of hydrocortisone and there was a close correlation between individual measurements of serum and urinary free cortisol (r = 0.885, p < 0.0001). Collection of urine samples offers certain advantages over repeated serum sampling and urinary free cortisol measurement may have a role in the assessment of hydrocortisone replacement therapy. PMID- 8458608 TI - On line continuous monitoring of subcutaneous tissue glucose is feasible by combining portable glucosensor with microdialysis. AB - A new method for continuous measurement of subcutaneous tissue glucose content is introduced: by combining the microdialysis technique with a wearable amperometric glucose sensor, a device for continuous glucose measurement in the subcutaneous tissue was obtained. This device was applied to healthy volunteers (n = 10) over the period of an oral glucose load and to type I diabetic patients (n = 10) under the conditions of daily life. Glucose profiles in both healthy and diabetic persons were followed in the subcutaneous tissue up to 27 hours. This technique will certainly open new perspectives of monitoring and treating diabetic patients. PMID- 8458609 TI - Potentiating effects of combined usage of three sulfonylurea drugs on the occurrence of alloxan diabetes in rats. PMID- 8458610 TI - Eicosapentaenoic acid prevents the inhibition of myo-inositol uptake induced by high glucose concentration in cultured human endothelial cells. PMID- 8458611 TI - Biphasic alteration of glucose transport in 3T3-L1 cells during differentiation to the adipocyte-like phenotype. AB - Glucose transport activity and subcellular distribution of glucose transporters, GLUT1 and GLUT4 were studied in non-confluent (NCF), confluent (CF), and differentiated 3T3-L1 cells (A). During growth of the fibroblasts to confluence, basal transport activity decreased to 20% of that in non-confluent cells. Corresponding with the reduction in transport activity, the abundance of GLUT1 in plasma membranes as normalized per cell decreased by 75% during growth of the cells to confluence. This effect was mainly due to a reduction of total cellular GLUT1. In addition, the portion of GLUT1 located in intracellular vesicles (low density microsomes) was moderately increased in confluent cells, and was further increased in cells differentiated to the adipocyte-like phenotype (in NCF 11%, in CF 24.5%, and in A 60% of the total GLUT1). GLUT4, in contrast, was approximately 10-times more abundant in low-density microsomes than in the plasma membranes of the differentiated cells. Insulin failed to stimulate glucose transport activity in non-confluent cells but produced an approximately 2-fold stimulation in confluent cells, probably through translocation of the GLUT1 from the intracellular compartment to the plasma membrane. In the differentiated adipocytes, insulin stimulated a 10-fold increase in glucose transport activity, the maximum levels approaching basal transport rates of non-confluent cells; both GLUT1 and GLUT4 were translocated in response to insulin. These data indicate that insulin sensitivity in 3T3-L1 cells develops in a biphasic pattern. In confluent fibroblasts, a moderate effect of insulin conferred exclusively by GLUT1 is detectable, probably reflecting the small intracellular compartment of GLUT1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458612 TI - Bone loss in experimental diabetes. Comparison with the model of inflammation mediated osteopenia. AB - Osteopenia occurs in diabetes mellitus. Since bone status is altered in Inflammation Mediated Osteopenia (IMO), it was appropriate to study its course in diabetic animals in order to investigate the mechanism of diabetic osteopenia. To this end, we compared the bone loss in streptozotocin (STZ) diabetes with that of IMO. Female rats were studied in total of 8 groups: Control, IMO, Diabetes, IMO with Diabetes (IMO-DIA) on the 3rd and similar groups on the 6th week after induction of IMO with 8 s.c. injections of talcum suspension. Femoral mineral content as reflected by ash weight per femoral volume after 3 weeks was lower in IMO compared to control rats (p < 0.05) while after 6 weeks this difference was not significant. The femur ash weight per volume of diabetic rats was lower than the one of intact rats with and without IMO both after 3 and 6 weeks. Diabetic rats with and without IMO exhibited no difference in this respect. Spleen weight as a measure of the extent of inflammation per body weight was increased only in the IMO group. The diabetic rats with and without IMO did not differ significantly with regard to spleen weight. Similar changes were observed 6 weeks after the induction of IMO. However the difference between IMO and diabetes rats was of borderline significance and no difference existed between the IMO and IMO diabetic group. The serum calcium levels of intact, IMO and diabetic rats showed no change during both experimental periods. Those of diabetic rats with IMO were higher than those of the diabetic and IMO animals after 6 weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458613 TI - Apolipoprotein E metabolism in sciatic nerves of diabetic rats. Implication for diabetic neuropathy. AB - Apolipoprotein (apo) E secreted by macrophages plays an important role in nerve injury and repair. We investigated the disturbance of neural apo E metabolism in diabetic rats and its relation to diabetic neuropathy. In BB/W rats, genetically diabetes prone rats, the secretion of apo E from sciatic nerves was 3-fold greater than that in control rats. Furthermore, a similar enhancement of apo E secretion was observed in injured nerves of STZ-induced diabetic rats (2-fold) as compared with those of nondiabetic rats, and this was reversible with insulin treatment. Histological examination of the nerves revealed more extensive infiltration of mononuclear cells in the injured nerves of STZ-induced diabetic rats than in those of non-diabetic rats. This is consistent with the findings that chemotactic activities for mononuclear cells, which were released from injured nerves, were greater in the STZ-induced diabetic rats than in the non diabetic rats. From these results we conclude that the recruitment of monocyte/macrophages into injured nerves is enhanced in diabetes, thereby causing derangement of neural apo E metabolism. These abnormalities might contribute to the development of diabetic neuropathy. PMID- 8458614 TI - Corticosteroid-binding globulin levels in the rat serum under conditions of starvation and restriction of motions. AB - Serum corticosteroid-binding globulin (CBG) concentrations were measured by a radioligand method in rats under the action of some factors influencing activity of pituitary-adrenal system. Basal CBG levels were about 2-fold higher in females than in males. In females only starvation resulted in a significant lowering of CBG activity, while in males CBG was affected only by restriction of motions for 5h Ether treatment in both sexes, pregnancy in females and adrenalectomy in males did not influence CBG levels. PMID- 8458615 TI - Acute metabolic effects of clonidine and adenosine in man. AB - Insulin resistance may contribute to non-insulin-dependent diabetes mellitus, hypertension, and dyslipidemia; increased free fatty acid concentrations could both promote and maintain this state of insulin resistance. Therefore, agents that inhibit lipolysis and decrease plasma concentrations of free fatty acids could be of therapeutic interest. We have measured metabolic effects of clonidine, an alpha 2 adrenergic agonist, and adenosine in healthy human subjects since human fat cells have alpha 2 and adenosine A1 receptors, which inhibit lipolysis in vitro. Clonidine, as expected, significantly lowered systolic and diastolic blood pressure; clonidine also decreased the plasma concentration of free fatty acids. Although clonidine caused a transient mild increase in plasma glucose, insulin and triglyceride concentrations were unchanged. The metabolic effects of adenosine were examined with two protocols. In the first study, volunteers received a graded infusion of adenosine (at 0, 10, 20, 50 and 100 micrograms/kg.min for 30 min/dose), and glucose, insulin, free fatty acids, as well as respiratory rate, systolic and diastolic blood pressures, and heart rate were measured. There was no change in glucose, insulin, or free fatty acid concentrations. In the second study a graded infusion was used and was maintained at 100 micrograms/kg/min for 120 minutes. Heart rate and respiratory rate significantly increased. Glucose and free fatty acid concentrations were unchanged, while insulin concentrations were significantly increased. All subjects had significant symptomatic complaints (dyspnea, chest pressure) during the adenosine infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458616 TI - The effects of glibenclamide on glucose homeostasis and lipoprotein metabolism in poorly controlled type 2 diabetes. AB - Six patients with type 2 diabetes underwent detailed metabolic studies before and after a minimum of 3 months' glibenclamide therapy. Treatment was associated with a small but significant increase in body weight. Despite improvements in almost all the measured parameters of glucose homeostasis (plasma glucose, glycosylated haemoglobin (HbA1), hepatic glucose production and insulin-mediated glucose disposal) neither fasting serum triglycerides nor HDL cholesterol changed and apoprotein A1 concentrations actually decreased significantly. NEFA and glycerol in fasting plasma and during the clamp studies did not change significantly with treatment. Post-heparin lipoprotein lipase and hepatic lipase activity did not change significantly. Thus, despite substantial improvements in glycaemic control and insulin sensitivity with sulphonylurea therapy, several aspects of lipid and lipoprotein metabolism remain largely unaffected. This small study suggests either that lipoprotein concentrations in type 2 diabetes are not influenced by insulin sensitivity or that the improvement is offset by another change that occurs during this form of therapy. It also suggests that other forms of therapy will be required to improve these cardiovascular risk factors in type 2 diabetes. PMID- 8458617 TI - Appeals court: HIV-infected surgeons can be liable for not informing patients ... Rossi v. Almarez. PMID- 8458618 TI - Managed care: where will your hospital fit in? AB - Despite unfulfilled predictions in the past, managed care has in recent years become a major form of health care delivery and financing, and could become the dominant form within a relatively short time. How will hospitals fit into a rapidly changing, managed care-driven delivery scenario? Beginning on page 18, Hospitals Contributing Editor Emily Friedman analyzes the current--and future- implications for the hospital field. PMID- 8458619 TI - Capitation and reform. Challenges and choices for hospital leadership. PMID- 8458620 TI - Strategic shakeup. CFOs prepare for a new age of hospital planning. AB - The reform-driven changes in health care delivery will also transform the strategic and financial planning process in hospitals. With that in mind, CFOs are working to best position their institutions for the anticipated changes. PMID- 8458621 TI - Living with capitation. Experts look at challenges of setting a prepaid rate. AB - A major goal of managed competition--changing incentives to encourage better delivery--will rely heavily on capitated payment, experts agree. But can capitation be applied correctly under managed competition? Achieving savings without suffocating healthy competition will be a challenge, say observers. PMID- 8458622 TI - Learning from experience. In AIDS treatment, knowledge means quality. AB - Recent clinical studies have revealed startling differences in mortality for AIDS patients in low- versus high-experience hospitals. But how can low-experience hospitals learn from high-experience ones? PMID- 8458623 TI - Factoring in the financials. Court gives nod to economic credentialing ... Rosenblum v. Tallahassee Memorial Regional Medical Center. PMID- 8458624 TI - Smart move: CEOs say succession planning up. PMID- 8458625 TI - Computerized patient records gain converts. PMID- 8458626 TI - Execs see shift in today's relocation package. PMID- 8458627 TI - Workers cite senior managers' low visibility. PMID- 8458628 TI - OTA takes closer look at cost of drugs. PMID- 8458629 TI - Data watch. Further growth projected in medical specialties. PMID- 8458630 TI - Ready, set, go: positioning for coming changes. PMID- 8458631 TI - Managed care or managed cost? PMID- 8458632 TI - The fate of protein antigen in earthworms: study in vitro. AB - Earthworm coelomocytes digest protein antigen in vitro. Proteolytic activity was detected both in cell-free coelomic fluid and in cell cultures of free coelomocytes which are effectors of earthworm immunodefense mechanisms. Antigen is cleaved either intracellularly or by proteolytic enzymes released by coelomocytes into the medium. Proteolysis was observed both in non-stimulated and antigen-stimulated cultures. Since significantly higher proteolysis was shown in supernatants from cultures of antigen-stimulated coelomocytes, we can assume that the release of proteolytic enzymes was inducible. PMID- 8458633 TI - Kinetics of development of spontaneous apoptosis in B cell hybridoma cultures. AB - The kinetics of the development of apoptosis was studied in mouse B cell hybridoma batch cultures carried out in the iron-rich protein-free medium. One of the markers of apoptosis, the apoptotic index reflecting the relative number of bodies insoluble in 6 M guanidinium hydrochloride, was found to rise significantly at 144 h, i.e., in the late stationary phase. At the decline of the culture (216 h) the value of the apoptotic index reached 29.1%. Analysis of another marker, the degree of DNA fragmentation determined on the basis of chromatographic resolution of isolated cellular DNA, revealed a significant increase as early as 96 h, i.e., at the end of the exponential phase. At 216 h the net value of the fragmented DNA fraction was about 30% of cellular DNA. The values of both markers were found to be very similar when the iron-rich protein free supplement was replaced with conventional 10% foetal calf serum. This finding suggested that the growth factors present in the serum were not able to abolish the tendency of the hybridoma culture to undergo spontaneous apoptosis. The timing of the spontaneous onset of apoptosis in the exponential phase indicated that B cell hybridoma apoptosis was a process associated with cell proliferation and full metabolic activity rather than with the decline of cell vitality. PMID- 8458634 TI - Activation of calcium (Ca)-dependent protein kinase C in aged mesenteric lymph node T and B cells. AB - We studied the effects of aging on the activities and translocation of Ca dependent protein kinase C (PKC) in resting mesenteric lymph node (MLN) T and B cells during the activation process induced by T and B cell mitogens and B cell stimulatory interleukins, including IL-4, IL-5 and IL-6. The activation process in senescent, resting (high density (HD)) MLN T cells is impaired, when these cells are stimulated with T cell mitogen, Con A. The defect in activation is associated with a reduction in both the new production of inositol-1,4,5 triphosphate (IP3) (an indicator for the production of intracellular free Ca) and the induction of Ca-dependent PKC. In contrast, the activation of the aged B cells with LPS plus/minus interleukins (IL-4, IL-5 and IL-6) is not impaired, being at least associated with a Ca-independent pathway of PKC activation. The elevated IP3 content and total (cytosol plus membrane) PKC activity in both resting T and B cells from aged MLN along with the greater difference in T cells than in B cells suggest that the in vivo Go cell cycle status of these cells may differ from that of the young, involving more in T cells. Finally, the MLN and splenic T cell Ca-dependent and B cell Ca-independent PKC activation do not differ between both age groups. PMID- 8458635 TI - Appearance of gamma delta T cell receptor-positive cells following alpha beta T cell receptor-positive cells in the lepromin reaction of human skin. AB - To elucidate the involvement of human gamma delta T cell receptor (TcR)+ cells in mycobacterial infection, we examined the kinetics of these cells in skin lesions of human lepromin reaction. The majority of CD3+ cells two days after induction of the lepromin reaction were alpha beta TcR+, while gamma delta TcR+ cells accounted for only 4.4 +/- 1.4% of the CD3+ cells. On day 21, the incidence of gamma delta TcR+ cells was greater (16.0 +/- 2.1%), although alpha beta TcR+ cells remained the predominant population. These kinetics of alpha beta TcR+ cells and gamma delta TcR+ cells contradict the 'early response, self surveillance' hypothesis for gamma delta TcR+ cells in mice. Most of the gamma delta TcR+ cells in this study of the lepromin reaction were V delta 1- V delta 2+ V delta 9+, and some of them proliferated in the skin lesions, suggesting that gamma delta TcR+ cells in the lesions may respond to mycobacterial antigens and may play an active part in the lepromin reaction. However, these gamma delta TcR+ cells were not correlated with granuloma formation, the size of necrotic areas, mycobacterial content, or the incidence of CD4+ cells and CD8+ cells. PMID- 8458636 TI - Analysis of cytolytic effector cell response in vitro against autologous human tumor cells genetically altered to synthesize interleukin-2. AB - Recently, there has been a surge of interest in gene therapy in cancer particularly with cytokine transduced tumor cells as a novel form of tumor vaccine. In two autologous human tumor systems, using the tumor cells engineered to produce interleukin-2 by gene transduction techniques, we have examined whether or not such genetically altered cells are capable of inducing a tumor specific cytolytic T cell (CTL) response, in vitro, in co-culture with the respective autologous peripheral blood lymphocytes (PBL). We found that in neither system did co-cultures of the IL-2 producing tumor cells and the autologous PBL generate much cytolytic effector cell activity directed against the respective tumor cells, although these co-cultures did lead to the generation of substantial levels of natural killer (NK) cell activity when measured against the prototype NK sensitive target K562 line. More surprisingly, the levels of lymphokine activated killer cell responses against the respective autologous targets that could be generated in the PBL with exogenous IL-2 alone were compromised by the presence of the autologous tumor cells in the co-culture. PMID- 8458637 TI - Identity of the major cysteine proteinase (cruzipain) from Trypanosoma cruzi and an antigen (Ag163B6) isolated with a monoclonal antibody. AB - Cruzipain, purified by conventional methods, and Ag163B6, isolated by affinity chromatography with a monoclonal antibody raised against a T. cruzi extract, are glycoproteins with a similar electrophoretic mobility, which reacted with sera from most chronic chagasic patients. Their behaviour in SDS-PAGE, Western blotting, isoelectric focusing, two-dimensional electrophoresis (IEF and SDS PAGE), Ouchterlony's double diffusion, and enzyme activity in SDS-PAGE gels containing 0.1% gelatin suggests that they are identical. PMID- 8458638 TI - Expression of major histocompatibility complex (MHC) class II antigens in the murine mammary gland. AB - Major histocompatibility complex (MHC) class II antigens were identified on cells within mammary gland connective tissue of lactating mice using a paraformaldehyde lysine-periodate-gluteraldehyde fixative and an immunoperoxidase staining method. The distribution of class II expressing cells within interalveolar and interlobular connective tissue was similar both throughout lactation and in successive lactations. Epithelial cells within secretory alveoli and mammary ducts did not express class II antigens. PMID- 8458639 TI - Effect of anti-gamma-interferon and anti-interleukin-4 administration on the resistance of mice against infection with reticulotropic and myotropic strains of Trypanosoma cruzi. AB - We studied the effect of in vivo administration of anti-gamma-IFN and anti-IL-4 monoclonal antibodies on the resistance of mice against myotropic and reticulotropic strains of Trypanosoma cruzi. Anti-gamma-IFN treatment augmented the susceptibility of mice when infected with the reticulotropic RA and Tulahuen strains of T. cruzi but did not alter the course of infection with the myotropic CA-I strain of the parasite. In vivo administration of anti-IL-4 enhanced the resistance of mice when infected with either Tulahuen or RA strains but did not affect the course of parasitemia when infected with CA-I. The possible biological relevance of these observations is discussed. PMID- 8458640 TI - Small artery structure in hypertension. Dual processes of remodeling and growth. PMID- 8458641 TI - Circadian rhythms of blood pressure after liver transplantation. AB - Twenty-four-hour systolic blood pressure, diastolic blood pressure, and heart rate profiles were recorded in 17 liver-transplanted patients by noninvasive ambulatory monitoring and were analyzed with the periodogram method. These recordings were compared with those of control subjects matched for age, sex, and daytime ambulatory blood pressure. Abnormal blood pressure patterns were found in seven of the 17 patients, whereas the other 10 patients had circadian blood pressure profiles that were not different from those of control subjects. These two groups of liver-transplanted patients did not differ in age, sex, oral dose of cyclosporine, specific serum cyclosporine level, and proportion of patients receiving azathioprine and antihypertensive medications. In contrast, the daily oral dose of prednisolone was significantly higher (p < 0.001) in the seven patients with abnormal circadian blood pressure patterns. Moreover, only the daily oral dose of prednisolone was inversely correlated with the magnitude of the nighttime systolic and diastolic blood pressure decrease (r = -0.64 and r = 0.66, p < 0.01). In contrast to blood pressure, patients and control subjects had similar circadian heart rate variations. We conclude that exogenous glucocorticoid administration may have a dose-dependent effect on the nighttime blood pressure fall and may play an important role in the pathogenesis of the abnormal circadian blood pressure profiles observed in liver-transplanted patients. PMID- 8458642 TI - Effects of hypertension and aging on coronary arteriolar density. AB - Coronary reserve has been shown repeatedly to be depressed in hypertension and aging. The underlying mechanisms remain elusive, but structural alterations of the coronary vasculature have been implicated. In this study, we measured maximal coronary dilator capacity and structural characteristics relevant to coronary resistance in aging normotensive (Wistar-Kyoto, n = 22) and spontaneously hypertensive rat (SHR) strains (n = 25) at 1.5, 4, 11, 16, and 22 months of age. Coronary flow measurements, using radiolabeled microspheres, demonstrated a significant (p < 0.01) hypertension- and age-related decline in maximal coronary dilator capacity. After flow measurements, vascular dimensions and arteriolar density were obtained from 1-micron sections prepared from perfusion-fixed hearts. A total of 10,012 arterioles were analyzed, 4,820 in hypertensive and 5,192 in normotensive rats. There was an 18-28% reduction in arteriolar density in hypertensive rats that specifically affected the terminal arteriolar bed at 1.5-11 months. However, the decrement in arteriolar density stabilized at 10% and 6% in 16- and 22-month-old hypertensive rats, respectively. Arteriolar density was not affected by aging. In both strains, there was a significant (p < 0.01) age-related decrease in the ratio of lumen diameter to wall thickness in arterioles > 50 microns. In addition, there was an overall 30% decrease (p < 0.01) in the ratio of lumen diameter to wall thickness in hypertensive compared with normotensive rats. These data indicate that both hypertension and aging are accompanied by structural alterations of the coronary resistance vasculature. These structural alterations may contribute to the depression in coronary reserve that complicates hypertension and aging. PMID- 8458643 TI - Glucocorticoid hypertension and nonadrenal phenylethanolamine N methyltransferase. AB - Several drugs that block epinephrine synthesis by inhibiting phenylethanolamine N methyltransferase (PNMT) lower blood pressure in hypertensive rats. We investigated the mechanism by which these drugs lower blood pressure in rats made hypertensive with the glucocorticoid dexamethasone. We performed adrenalectomy or sham operation on several rats and then gave them either dexamethasone chronically or vehicle. The dexamethasone-treated adrenalectomized rats also received either the centrally acting PNMT inhibitor SKF 64139 chronically or an equal dose of the primarily peripherally acting PNMT inhibitor SKF 29661. Both SKF 64139 and SKF 29661 reduced blood pressure by more than 25 mm Hg. SKF 64139 also reduced PNMT activity in hypothalamus, medulla oblongata, skeletal muscle, and cardiac atria and ventricles; SKF 29661 inhibited PNMT in muscle and heart tissue by 40-75%, did not inhibit PNMT in hypothalamus, and inhibited PNMT by only 29% in medulla oblongata. PNMT activity in peripheral tissues was also more highly correlated with blood pressure than was PNMT activity in the brain areas studied. Neither drug reduced tissue epinephrine levels, but SKF 64139 elevated dopamine or norepinephrine levels or both in several tissues. We conclude that the blood pressure-lowering action of PNMT-inhibiting drugs in glucocorticoid hypertensive rats may be due to inhibition of peripheral nonadrenal PNMT. We speculate that elevations in nonadrenal PNMT may mediate glucocorticoid hypertension. PMID- 8458644 TI - Enhanced renal angiotensin II subtype 1 receptor responses in the spontaneously hypertensive rat. AB - Results from renal transplantation experiments demonstrate that a renal defect is responsible for the development of hypertension in the spontaneously hypertensive rat (SHR). In addition, studies with inhibitors of the renin-angiotensin system have shown that angiotensin II (Ang II) is required for the development and maintenance of hypertension in the SHR. These observations prompted us to propose the hypothesis that hypertension in these rats is due to an enhanced renal responsiveness to Ang II. The purpose of the present study was to determine whether an enhanced renal responsiveness to Ang II exists in adult (12- to 14 week-old) SHR relative to Wistar-Kyoto control rats. To prevent hypertension induced changes in renal function in SHR, we maintained both strains in the normotensive state from 4 weeks of age with long-term captopril treatment (100 mg/kg per day). Intrarenal Ang II infusions induced a significantly greater decrease in renal blood flow and glomerular filtration rate and a significantly greater increase in renal vascular resistance in SHR compared with Wistar-Kyoto rats. DuP 753 (Ang II subtype 1 [AT1] receptor antagonist), but not PD 123177 (Ang II subtype 2 receptor antagonist), blocked the renal responses to Ang II in SHR, suggesting that the enhanced renal responsiveness to Ang II was mediated solely by the AT1 receptor subtype. Unlike renal responses to Ang II, renal responses to periarterial renal nerve stimulation were similar in both strains, suggesting a selective renal hyperresponsiveness to Ang II in the SHR rather than a general hyperresponsiveness toward all vasoconstrictors. From these studies in chronically captopril-treated rats, we conclude that 1) SHR have a genetically determined, enhanced renal responsiveness to Ang II; 2) the enhanced renal responsiveness to Ang II is mediated by the AT1 receptor; and 3) renal responses to periarterial nerve stimulation are not significantly enhanced, suggesting a selective hyperresponsiveness to Ang II in the kidneys of SHR. PMID- 8458645 TI - Estrogen receptor variant and hypertension in women. AB - Eighty-eight women visiting a gynecologist were tested for an estrogen receptor B variant allele. The women were ethnically and racially homogeneous to a large degree. They were from a suburb of Long Island, and most were white. The 12% incidence of hypertension in women with the estrogen receptor wild-type allele is comparable to the 13-32% incidence in the general population of women aged 55-64 years. However, the 48% incidence of hypertension in women with the estrogen receptor B-variant allele is considerably higher than in the general population of women in this age group. We conclude that the presence of the estrogen receptor B-variant allele might have increased the prevalence of hypertension in the women in this study. PMID- 8458647 TI - Reflex vasopressin and renin modulation by cardiac receptors in humans. AB - Animal studies have shown that vasopressin secretion is modulated by arterial baroreceptors and cardiopulmonary volume receptors. Whether this is the case also in humans is controversial, however. To determine whether vasopressin is reflexly modulated by cardiac volume receptors, we studied the effect on plasma vasopressin (venous blood, radioimmunoassay) of reducing venous return and left ventricular end-diastolic diameter (echocardiography) by producing a 20-minute lower body negative pressure in 14 healthy subjects (aged 49.3 +/- 3.8 years, mean +/- SEM). The data were compared with those of 14 age-matched heart transplant recipients, i.e., subjects with cardiac denervation. In healthy subjects, lower body negative pressure at -15 mm Hg caused a modest reduction in left ventricular end-diastolic diameter (-5 +/- 3.4%) and no change in vasopressin, whereas lower body negative pressure at -37.5 mm Hg caused a more marked reduction in left ventricular end-diastolic diameter (-12 +/- 2.5%) and a small, variable, but overall statistically significant (p < 0.05) increase in vasopressin (+145 +/- 46%, p < 0.01). The left ventricular end-diastolic diameter changes induced by the two lower body negative pressure stimuli were similar in heart-transplant recipients, but the vasopressin increase seen with the lower body negative pressure at -37.5 mm Hg was abolished. The marked increase in plasma renin activity and forearm vascular resistance induced by lower body negative pressure in healthy subjects was also abolished or drastically attenuated in heart-transplant recipients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458646 TI - Regulation of vascular angiotensin release. AB - To investigate the regulatory mechanism of the vascular renin-angiotensin system, we perfused isolated rat hind legs with plasma-free buffer and quantified angiotensin peptides in the perfusate. Angiotensin release from hind legs was increased in rats pretreated with losartan (DuP 753) and rats fed a low sodium diet with subsequent furosemide and was decreased in nephrectomized rats and rats given dexamethasone, ethynylestradiol, and triiodothyronine. Using these models, we have attempted to identify which step or component of angiotensin metabolism determines angiotensin release level. Changes caused by these manipulations in plasma renin concentration and basal angiotensin release from hind legs were almost parallel, whereas plasma angiotensinogen concentration and the angiotensin release changed in opposite directions. Infusion of renin in hind legs caused a marked increase in angiotensin release and continued even 1 hour after cessation of renin infusion. Infusion of angiotensinogen did not alter the angiotensin release. Angiotensin clearance and angiotensin I conversion were not affected by either nephrectomy or losartan pretreatment. Aortic renin messenger RNA level was extremely low and not increased by nephrectomy or losartan pretreatment, although kidney renin messenger RNA level was increased by losartan pretreatment. These results provide evidence that plasma renin of kidney origin is the major source of vascular functional renin and plays the determining role in the regulation of vascular angiotensin release. Plasma-derived or locally produced angiotensinogen, locally produced renin, converting enzyme, and angiotensin clearance are not considered to be the primary determinant in the regulation of vascular angiotensin release in these acute and subacute experimental models. PMID- 8458648 TI - Age and gender influence muscle sympathetic nerve activity at rest in healthy humans. AB - Muscle sympathetic nerve activity at rest increases with age in humans. The respective influences of the aging process per se and gender on this increase and whether age and gender effects on muscle sympathetic nerve activity can be identified with plasma norepinephrine concentrations, however, have not been established. To examine these issues, nine young women (aged 24 +/- 1 years; mean +/- SEM), eight young men (aged 26 +/- 1 years), seven older women (aged 63 +/- 1 years), and eight older men (aged 66 +/- 1 years) were studied. All were healthy, normotensive (blood pressure < 140/90 mm Hg), nonobese (< 20% above ideal weight), unmedicated, nonsmokers engaged in minimal to recreational levels of chronic physical activity. Arterial blood pressure (manual sphygmomanometry, brachial artery), heart rate, muscle sympathetic nerve activity (peroneal microneurography), and antecubital venous plasma norepinephrine concentrations (radioenzymatic assay) were determined during quiet supine resting conditions. Body weight was higher in men, but there were no age-related differences, whereas estimated body fat (sum of skinfolds) was higher in women and in the older groups (p < 0.05). Estimated daily energy expenditure, arterial blood pressure, and heart rate were not different among the groups. Both muscle sympathetic nerve activity burst frequency and burst incidence at rest were progressively higher in the young women, young men, older women, and older men (10 +/- 1 versus 18 +/- 2 versus 25 +/- 3 versus 39 +/- 5 bursts/min and 16 +/- 1 versus 30 +/- 4 versus 40 +/- 3 versus 61 +/- 6 bursts/100 heartbeats, respectively; all p < 0.05 versus each other).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458649 TI - National standard for measurement of resting and ambulatory blood pressures with automated sphygmomanometers. AB - The Association for the Advancement of Medical Instrumentation develops voluntary standards for medical devices so that manufacturers might provide information on their product and basic safety and performance criteria that should be considered in qualifying the instrument for clinical use. American national standards are generated through a consensus process by committees consisting of experts in research, development, and design from user, industry, and government communities. Draft standards are made available for public review and may become American national standards after review by the American National Standards Institute. The first American national standard for electronic and automated sphygmomanometers was published in monograph form in 1987. The objective of the revised 1992 standard for electronic and automated sphygmomanometers is to provide updated labeling, safety, and performance requirements that help ensure that consumers and health care professionals are supplied with safe, accurate devices for the indirect measurement of blood pressure, including ambulatory blood pressure recorders. This standard permits validation of the automatic or electronic device by comparison with either direct, intra-arterial blood pressure measurements or the noninvasive cuff/stethoscope technique, based on Korotkoff sounds identified by individuals trained in auscultation. This summary report of the 1992 American national standard for automatic sphygmomanometers provides recommendations for the methods of comparison, statistical analysis of the data, presentation of the results, and criteria for acceptability. Users, researchers, and instrument designers should refer to the American national standard monograph for detailed requirements. PMID- 8458650 TI - Ambulatory blood pressure monitoring use in hypertension research and clinical practice. PMID- 8458651 TI - Pulse pressure and microvessels. PMID- 8458652 TI - 10th Scientific Meeting of the Inter-American Society of Hypertension. La Jolla, California, April 25-29, 1993. Abstracts. PMID- 8458653 TI - Neurotoxicity induced by exposure to toluene. An electrophysiologic study. AB - The object of the present study was to evaluate, with the aid of electrophysiologic techniques, the alterations induced in the auditory nervous system by exposure to toluene in a group of rotogravure workers. From 300 workers who were apparently in good health but were professionally exposed to toluene, we selected a sample of 40 workers of normal hearing ability. They were examined with an adaptation test studied by the brainstem auditory evoked potential technique with 11 and 90 stimulus repetitions a second. The results were compared with those in a group of workers of the same age but not professionally exposed to solvents. Our study demonstrates that exposure to toluene is able to induce a statistically significant alteration in the electric responses with both 11 and 90 stimuli repetitions. This alteration can be explained as a toluene exposure induced modification, of physiologic stimulus conduction mechanisms, even in the absence of any clinical sign of neuropathy. Furthermore, such a modification could be observed in the electric responses of the entire auditory system, from peripheral receptors to brainstem nuclei. PMID- 8458654 TI - Short-term respiratory function changes in relation to workshift welding fume exposures. AB - The forced vital capacity (FVC), the forced expiratory volume in one second (FEV1) and the transfer factor for the lung (TL) were measured before and after the 8-h work shift in groups of welders and non-welder controls in a shipyard. For each subject, full-shift average concentrations of welding fume constituents were evaluated. On the average, the lung function indices in both groups of welders and controls decreased from morning through afternoon. The welders demonstrated more reduction in the indices than the control group. In general, there was no significant association between the acute changes in the lung function and the daily amount of exposure to welding fume constituents or the welding environmental factors. However, the overall difference of mean diurnal variations in TL between the groups working under different ventilation condition was significant (P < 0.01). On the average, welders who did not use any ventilation system showed maximum reduction in TL value. Acute reduction of FEV1 was positively correlated (P < 0.05) with the levels of iron oxide produced during welding. PMID- 8458655 TI - Analysis and stability of phenylglyoxylic and mandelic acids in the urine of styrene-exposed people. AB - In this work a high-performance liquid chromatographic method is described that is reliable and practical for use in routine biological monitoring of exposure to styrene. The method uses a modern diode array detection technique by which mandelic and phenylglyoxylic acids can be measured simultaneously using different wavelengths. The liquid chromatographic method was compared to a gas chromatographic method developed for the analysis of mandelic, phenylglyoxylic and para-hydroxymandelic acids. The methods gave results consistent with each other. These two methods were then used to check the stability of the main metabolites of styrene, especially of phenylglyoxylic acid, in urine samples stored at +6 degrees C or at -18 degrees C for periods up to 70 days. None of the frozen samples showed any significant decrease in the phenylglyoxylic acid concentration, whereas at 6 degrees C one of the samples showed a reduction of 46% after 1 month. PMID- 8458656 TI - Individual and work-related risk factors associated with symptoms of musculoskeletal complaints. AB - Individual and work-related risk factors in the development of occupational musculoskeletal complaints were investigated in a cross-sectional study of 52 female production workers and 34 female office workers. The work tasks of the production workers were considered to generate shoulder muscle loads of low amplitude and high repetitiveness, and the work tasks of the office workers, muscle loads of low amplitude and low repetitiveness. The symptom scores were similar in the two groups, with the highest score for both groups in the shoulder neck region. Previous pain symptoms were an important risk factor for musculoskeletal pain in all body regions, whereas psychosocial problems at work were a risk factor for complaints in the shoulder-neck region. For the office workers, 27% of the variance in shoulder-neck symptoms was explained by the variance in the parameters "previous pain symptoms" and "psychosocial problems" in a multilinear regression model. In three groups of workers with different physical loads on the shoulder muscles the symptom scores for workers without previous pain symptoms and psychosocial problems were related to the physical load. For workers with previous pain symptoms and psychosocial problems, the symptom scores were high and similar for all three groups. PMID- 8458657 TI - Trapezius muscle load as a risk indicator for occupational shoulder-neck complaints. AB - Upper trapezius muscle activity was quantified by electromyographic (EMG) recordings using surface electrodes to study occupational muscle load as a risk indicator for the development of shoulder-neck complaints. Thirty-nine female production workers and thirty-two female office workers showed much larger interindividual differences than the mean difference in muscle activity between the two groups. By comparison with the production workers, the muscle activity patterns of the office workers were characterized by more short pauses and a lower static load. The median load level was similar for the two groups. For the office workers, but not for the production workers, weak correlations were found between symptoms of pain in the shoulder-neck region and some of the EMG parameters (static level and frequency of micropauses > 0.6 s. Current techniques for measuring shoulder muscle load by EMG recordings seem inadequate as screening methods to predict future risk of development of muscle pain symptoms. PMID- 8458658 TI - Effects of smoking and drinking on excretion of hippuric acid among toluene exposed workers. AB - In order to investigate possible effects of smoking and drinking on the metabolism of toluene in occupational settings, 206 toluene-exposed men (mean age: 31.4 years) in shoemaking, painting, or surface-coating workshops together with 246 nonexposed control men (36.8 years) were studied for the time-weighted average intensities of exposure to toluene, hippuric acid concentration in shift end urine samples, and the two social habits of smoking and drinking. The mean daily consumptions of cigarettes and ethanol were about 20 pieces and 10 g among smokers and drinkers, respectively. The geometric mean toluene concentration among the exposed subjects was about 20 ppm, with a maximum of 521 ppm. Regression analysis after classification of the subjects by smoking and drinking clearly demonstrated that the two social habits, when combined, markedly reduce the hippuric acid level in the urine of workers exposed to toluene. There was a significant association between smoking and drinking habits, which hindered separate evaluation of the effects of the two habits on toluene metabolism. Comparison of the present results with the findings reported in the literature, however, suggested that the observed effects may be attributable to smoking rather than to drinking habits. PMID- 8458659 TI - Danish external quality assessment scheme: an interlaboratory comparison study on lead, cadmium and chromium in lyophilized human blood concentrate. AB - A Danish External Quality Assessment Scheme (EQAS) was carried out by the Danish National Institute of Occupational Health during the period 1988-1992. The scheme was implemented for 29 international laboratories from 15 countries assaying lead, cadmium, and chromium in human blood to ascertain the systematic error and uncertainty of the analytical methods. In the survey the quality control material AMI B701-B705, based on lyophilized human whole-blood concentrate, were used. As an estimate of the true values the reference values used in this evaluation were (a) the computed values, i.e., sum of the basal and spiked trace element concentration, and (b) the consensus values normally used in the Danish EQAS. This international evaluation of lead, cadmium, and chromium in human blood demonstrated that the use of lyophilized human blood concentrate quality control materials combined with this scheme is valuable in estimating the systematic error and the uncertainty of the analytical methods. For evaluating analytical performance, the computed values were preferable to the consensus values for lead and cadmium in human blood. Due to analytical difficulties suitable reference values were not established for chromium in blood. The study revealed analytical difficulties for cadmium and chromium in human blood. The assessment of laboratories according to established performance indexes indicates that few laboratories can maintain these performance indexes. PMID- 8458660 TI - An evaluation of the significance of mouth and hand contamination for lead absorption in lead-acid battery workers. AB - The present study was conducted to evaluate the role of ingestion through hand and mouth contamination in the absorption of lead in 25 lead-acid battery workers. Levels of personal exposure to airborne lead ranged from 0.004 to 2.58 mg/m3 [geometric mean 0.098, with 25% of samples exceeding threshold limit values (ACGIH) of 0.15 mg/m3]; the mean (SD) blood lead level was 48.9 (10.8) micrograms/dl. Mean hand lead contents increased 33-fold from preshift levels on Monday mornings (33.5 micrograms/500 ml) to midshift levels on Thursday afternoons (1121 micrograms/500 ml). Mouth lead contents increased 16-fold from 0.021 micrograms/50 ml on Mondays to 0.345 micrograms/50 ml on Thursdays. The typical Malay racial habit of feeding with bare hands and fingers without utensils (closely associated with mouth and hand lead levels on Mondays) explained the bulk of the variance in blood lead levels (40%), with mouth lead on Thursdays (closely associated with poor personal hygiene) explaining a further 10%. Air lead was not a significant explanatory variable. The implementation of a programme of reinforcing hand-washing and mouth-rinsing practices resulted in a reduction of the blood lead level by 11.5% 6 months later. These results indicate that parenteral intake from hand and mouth contamination is an important cause of lead absorption in lead-exposed workers. PMID- 8458661 TI - Subclinical affection of liver and kidney function and solvent exposure. AB - The role of solvents as hepato- and nephrotoxic agents under present-day exposure levels is still unclear. The purpose of this study involving 99 metal degreasers was to examine dose-response relationships between long-term exposure of mainly trichloroethylene and a battery of liver function tests and one nephrotubular enzyme test. Serum gamma-glutamyltransferase and urinary N-acetyl-beta glucosaminidase were elevated by increasing solvent exposure at bivariate level. The significance of this relationship, however, was not able to withstand a multiple regression analysis, with age and alcohol abuse as confounding variables. The conclusion is that of a nonsignificant association between solvent exposure and tests screening for early liver and kidney dysfunction. PMID- 8458662 TI - A nested case control study of lung cancer among New York talc workers. AB - This nested case control study assessed the relationship of lung cancer and time exposed to talc, while controlling for smoking, other talc exposures, and nontalc exposures. There were 22 lung cancer cases (91% smokers and 9% former smokers) and 66 controls (27% nonsmokers, 9% former smokers, and 64% smokers). Smokers were at sixfold increased risk compared to nonsmokers and ex-smokers. When stratified by smoking status, risk of lung cancer decreased with talc tenure and remained negative when excluding cases with < 20 years' latency and short-term workers. These data suggest that nontalc exposures are not confounding risk factors while smoking is, and that temporal and exposure-response relationships are consistent with a smoking etiology but not an occupational etiology for lung cancer. PMID- 8458663 TI - Respiratory symptoms and ventilatory capacity in workers in a vegetable pickling and mustard production facility. AB - A group of 117 women occupationally exposed in a pickling factory were studied for the prevalence of acute and chronic respiratory symptoms and lung function changes. Workers were studied by task which included (1) pickling, (2) mustard making, and (3) packing. Similar prevalences for all respiratory symptoms were seen for the three workers groups, with all groups having significantly higher prevalences of chronic cough (P < 0.05), chest tightness, nasal catarrh, and sinusitis (P < 0.01) than a nonexposed control group from a bottling plant. Prevalences of acute symptoms were greater for pickling than for mustard or packing workers. Measured forced expiratory volume in 1 s and maximum flow rates at 50% and the last 25% of the control vital capacity were in general significantly lower than predicted values for the worker subgroups. Pickling workers exposed for more than 1 year in the industry had greater across-shift reductions for all spirometric parameters tested than those workers exposed for 1 year or less. Our data suggest that extended occupational exposure in the pickling industry results in acute exposure-related respiratory effects and ultimately may lead to the development of chronic respiratory symptoms and changes in baseline lung function. PMID- 8458664 TI - Effects of grip and push forces on the acute response of the hand-arm system under vibrating conditions. AB - The purpose of the occupational medicine component of a joint research project was to study the effects of grip and push forces on the acute reaction of the hand-arm system under vibrating conditions. Several series of experiments were carried out by means of a vibration simulator in a laboratory environment in order to study biodynamic vibration behaviour, muscle response, skin temperature, shifts of the vibration perception threshold and the intensity of subjective vibration perception; in addition, field tests with hammer drills were conducted. On the whole, the findings obtained suggest that the coupling of the hand with the handle involved in using vibrating tools has a considerable impact on the stresses to which the hand-arm system is exposed. For this reason, future national and international rules and regulations on vibration assessment should take into consideration the effects of variations in coupling intensity. PMID- 8458665 TI - The subcutaneous administration route of epoetin: advantages, pain at the injection site and patient acceptance. PMID- 8458667 TI - Spectrum of poisoning requiring haemodialysis in a tertiary care hospital in India. AB - We report our experience in 66 cases of acute poisoning requiring haemodialysis (HD) in the last 17 years. Barbiturate poisoning was the commonest poisoning (30 cases). Mean blood barbiturate level was 8.9 mg%. Twenty four were in grade IV coma at the time of presentation. Twenty five required one HD and 5 cases needed 2 HD. Four died due to respiratory infection or hypotension. Copper sulphate poisoning was encountered in 19 cases. Common features in this group were: acute renal failure (ARF) (19), haematuria (3), gastrointestinal bleeding (7), intravascular haemolysis (9), jaundice (11), hepatocellular toxicity (8), methaemoglobinuria (8) and circulatory collapse (5). The indication for HD in all these cases was ARF. Seven patients died. There were 9 cases of mercuric chloride poisoning requiring 2-5 HD. Common features in this group were; ARF (9), gastrointestinal bleeding (9), anaemia (8), jaundice (2). Two patients died. Other patients had Mandrax, Naphthalene, Tincture Iodine, Ethylene Bromide and Lithium poisoning. Overall mortality in our study was 24.2%. It is concluded that HD is not the primary mode of therapy for drug intoxication. Adequate supportive management is most important in determining final outcome of these patients. PMID- 8458666 TI - Combined treatment in Wegener's granulomatosis with crescentic glomerulonephritis -clinical course and long-term outcome. AB - This study reports on 9 patients suffering from Wegener's granulomatosis (WG) with crescentic GN and severe systemic manifestations. On admission the mean serum creatinine was 10.9 +/- 5.1 mg/dl (4-20 mg/dl); 8 patients were oliguric and required dialysis treatment. Renal biopsy showed crescents in all cases, involving 66 to 100% of glomeruli. Patients were treated with a protocol including: a plasma exchange (PE) course; methylprednisolone; cyclophosphamide; and an antithrombotic agent (defibrotide). Clinical picture and renal function progressively improved in all patients within the first 4 weeks of treatment. After 1 month serum creatinine was 2.7 +/- 0.8 mg/dl and dialysis was no longer needed in any patient. Five relapses occurred in 3 patients 12-26 months after the onset of the disease, while they were still receiving immunosuppressive treatment. At follow-up (22 to 112 months: mean 71) all patients were alive with no clinical signs of disease activity. One patient was on regular dialysis while the others had a serum creatinine of 1.2-2.8 mg/dl (mean 1.9). Our results confirm that crescentic GN associated with WG can be successfully treated even when associated with severe clinical picture and suggest that PE can contribute to control the disease without increasing immunosuppression. PMID- 8458668 TI - Cardiac pathology in patients with end-stage renal disease maintained on hemodialysis. AB - We report the spectrum of cardiovascular pathology found on autopsy examination in 106 consecutive patients with end-stage renal disease. Cardiovascular pathology was present in nearly all patients, and was the most frequent cause of death (36%), with acute myocardial infarction accounting for 15%. Particularly frequent pathologic findings were left ventricular hypertrophy, coronary and aortic atherosclerosis, pericarditis with effusion, myocardial fibrosis, and valvular dilatation. Cardiovascular death rate was higher during the first year than after the fifth year of dialysis. Nearly all patients had a history of hypertension. The nature of the underlying cause of renal failure and pre existing cardiovascular disease, specifically diabetes mellitus and hypertension, were the principal predictors of cardiovascular mortality rather than maintenance hemodialysis therapy per se. PMID- 8458669 TI - Maintaining the patency of double-lumen silastic jugular catheters for haemodialysis. AB - A system has been developed for maintaining the patency of double lumen silastic jugular catheters in patients with refractory vascular access problems. Most patients receive a small daily dose of aspirin. Selected patients also receive warfarin to maintain a prothrombin time (PT) of 15, 20, or 30 seconds. Inadequate blood flow due to thrombus obstruction can be overcome by the intravenous administration of urokinase, 250.000 units. This can be administered safely to outpatients provided that heparin is not given simultaneously. Occasionally a second dose may be required. By adopting this policy all catheter obstructions have been overcome. The danger of iatrogenic bleeding cannot be discounted. Warfarin therapy must be very closely monitored. PMID- 8458670 TI - Protein C, protein S and antithrombin III metabolism in dialysis patients. PMID- 8458671 TI - Emphysematous pyelonephritis and cystitis in a renal transplant recipient- computed tomographic appearance. AB - A 35-year-old nondiabetic renal allograft recipient developed emphysematous pyelonephritis and cystitis emphysematosa necessitating graft nephrectomy. The patient received cyclosporin and prednisolone as immunosuppressive therapy. He developed the first episode of urinary tract infection one week after transplantation and another episode 3 months later. Abdominal CT scan revealed presence of gas in the graft kidney, urinary bladder, and surrounding tissues. Despite appropriate antibiotic therapy, his renal function deteriorated rapidly and he died on the first postoperative day. PMID- 8458672 TI - Different stroke volumes for the left and right ventricles in the moving-actuator type total artificial heart. AB - A new electromechanical moving-actuator type total artificial heart (TAH) has been developed to solve the imbalance problem without an extra compliance chamber. A different stroke volume was achieved by the large left sac size and the asymmetry of the actuator motion referred to the center position. The left ventricle consists of a double sac with the outer sac attached to the actuator providing active diastolic filling, while the double sac of the right ventricle being free from the actuator, and having sufficient suction produced due to the rigid pump housing. The stroke volume difference between the left and right sac is compensated through the air in the interventricular space of the variable volume (VV) space. Computer simulation based on the geometrical relationships between the blood sacs and the actuator was performed to simulate the physical mechanisms of the moving-actuator type TAH. Results were then compared with the measured pressure changes in various chambers of the pump and the stroke volume differences in mock circulation test. In two acute calf experiments, the balanced left and right atrial pressures were achieved in the moving-actuator type TAH without an extra compliance chamber. PMID- 8458674 TI - Parathyroidectomy in secondary (renal) hyperparathyroidism--whom, when, how? PMID- 8458673 TI - A simulation study on a self-tuning portable controller of blood glucose. AB - A self-tuning, nonlinear controller was developed to drive portable or implantable micro-pumps for blood glucose control in diabetic subjects. The parameter estimation is based on a recursive least-square algorithm applied to a discrete time simplified mathematical model of the glucose system; the controller, which is integrated with the estimator, uses an extended minimum variance method. The software was designed to drive a micro-controller wearable unit, operating with different kinds of glucose sensors, in order to perform chemical and biological experimentations. Some strategies were introduced to avoid hypoglycaemia, even tolerating a reduction in control speed and accuracy. The whole system was tested in a simulation study, performed on a mathematical model implemented on a personal computer. The tests were performed while simulating different controller structures and settings, and patient responses. They showed a satisfactory control behaviour, mostly as far as stability and robustness are concerned, in all simulated conditions. PMID- 8458675 TI - Comparison of intranasal versus intravenous verapamil bioavailability. AB - Intranasal verapamil administration may limit intrasubject variability encountered due to the metabolism differences of the d and l-isomers. We simultaneously measured verapamil/norverapamil concentrations, PR interval, heart rate (HR), and mean arterial pressure (MAP) in six healthy volunteers receiving verapamil 5 mg intranasally and intravenously on two separate occasions. Two subjects achieved measurable verapamil concentrations after intranasal administration with a mean bioavailability of 16.1%. Intranasal bioavailability was limited secondary to instillation volume. No relationship between HR, MAP and verapamil concentration was noted. A relationship between mean intravenous verapamil concentration and mean PR interval was observed; however, extensive interpatient variability existed: two subjects demonstrated enough counterclockwise hysteresis to skew mean data. Mean data may falsely represent the verapamil concentration-effect relationship. Intranasal verapamil administration is limited by instillation volume. Development of a concentrated dosage form is necessary to assess bioavailability. Concentration-effect relationships are more accurately described using individual, rather than mean data. PMID- 8458676 TI - Iron protein succinylate: preclinical safety assessment. AB - In this brief review the preclinical safety studies on iron protein succinylate (synonym: ITF 282) are presented. Iron protein succinylate is an iron-protein complex, in which iron is present in ferric form. It has been developed for oral iron-supplementation therapy and is characterized by a very favorable tolerability profile. The acute toxicity of iron protein succinylate to rodents is very low, indicating a substantial margin of safety with respect to accidental child poisonings. In chronic toxicity studies of 52-week duration in rats and dogs, there were no findings of toxicological significance. In particular, there were no alterations in hematological parameters and no histopathological findings consistent with iron overload damage. Some deposition of iron was noted in the spleen and liver of the treated dogs. A series of reproductive toxicology studies were performed to assess the effects on fertility (in the rat), peri- and postnatal reproductive function (in the rat) and fetal toxicity (in the rat and the rabbit). Treatment with iron protein succinylate did not result in any adverse effect on reproductive performance nor did it affect the incidences of malformations, visceral and skeletal anomalies or skeletal variants. There was no evidence of mutagenic activity in a comprehensive series of in vitro and in vivo mutagenicity studies. No secondary pharmacological effects of the product were noted in a wide range of single and repeated administration studies. Overall, the available toxicology and safety profile of this product offers ample assurances of the safety of iron protein succinylate in clinical use. PMID- 8458677 TI - Effect of anti-epileptic drugs on serum zinc and copper concentrations in epileptic patients. AB - Serum concentrations for zinc and copper were determined in epileptic patients who had undergone one month of therapy with a mono-antiepileptic drug (mono-AED) (carbamazepine, CBZ; phenobarbital, PB; phenytoin, PHT; valproic acid, VPA). There were 114 epileptic patients and 30 healthy volunteers who participated in this study. Although zinc concentrations tended to decrease, there were significant increases in copper concentrations in patients who were treated with mono-AED (CBZ, 32.9%; PB, 36.4%; PHT, 39.0%; VPA, 25.4%) when compared with healthy volunteers. There was no significant change in either zinc or copper concentrations among the four mono-AED groups. No dose-related changes could be observed either for zinc or copper concentrations. In conclusion, this study demonstrated that both zinc and copper concentrations in epileptic patients under chronic AED therapy differed somewhat from the control level, but remained within the normal range, indicating that there is no need to adjust serum concentrations of either of these trace elements in order to treat diseases related to them. PMID- 8458678 TI - A survey on drug-related hospitalization in a community teaching hospital. AB - We retrospectively studied 2,695 patients admitted to the Department of Medicine over a 10-month period in 1990 to determine the incidence of drug-related hospitalization. A drug-related problem was identified as the primary cause of hospitalization in 109 (4.0%) admissions. The incidence was significantly greater in the elderly group as compared with the non-elderly group (5.2% vs 3.2%). Non steroidal anti-inflammatory drugs, hypoglycemic agents, herbal medicine, adrenocorticosteroids and antihypertensive drugs were most often involved. The five most common adverse events were upper gastrointestinal tract bleeding, skin rashes, hypoglycemia, hypercorticism and hepatitis. Iatrogenic disease was fatal in 2 cases. Patients used drugs without medical supervision in 45 cases. In view of the increasing complexity of modern pharmacotherapy and the popularity of self medication in our society, educational efforts should be enhanced for medical professionals and the general population to reduce the risk of drug-related hospitalization. PMID- 8458679 TI - Phase 1 study of L-627, biapenem, a new parenteral carbapenem antibiotic. AB - The safety and pharmacokinetics of L-627, a new injectable carbapenem antibiotic, were evaluated in healthy volunteers. In single-dose studies, 20, 40, 80, 150, 300 and 600 mg of L-627 were administered by i.v. infusions over 1 hour. Plasma concentration-time profiles were well described with a two-compartment open model. The half-life of elimination from plasma was 1.3 +/- 0.8 (mean +/- SD) hour, and the Cmax and AUC paralleled the doses given. The mean urinary recovery of unchanged L-627 within the first 12 hours was 63.1 +/- 2.7% of the dose. In the multiple-dose studies, 300 mg of L-627 (i.v. over 1 hour) was administered every 12 hours, 11 times in total and 600 mg of L-627 was administered every 12 hours, 9 times in total. No discernible accumulation of the drug in plasma was observed. There were no subjective or objective abnormal findings definitely attributable to the drug except that one subject in one of the multiple-dose regimens (300 mg b.i.d.) showed only a slight elevation of transaminase value, although the elevated value promptly recovered after completion of dosing. No abnormality was observed in the other multiple-dose regimen (600 mg b.i.d.). From these results, L-627 was concluded to be safe and well tolerated. PMID- 8458680 TI - Analysis of oral fosfomycin calcium (Fosmicin) side-effects after marketing. AB - For about 6 years after the marketing of oral formulations of fosfomycin calcium (FOM-Ca) in December, 1980, we collected the data on 35,481 cases and analyzed it regarding safety. Primary side-effects consisted mainly in gastrointestinal disturbances, damage to skin and adnexa, liver and bile duct disorders. Specifically, diarrhea, nausea, abdominal pain, anorexia, eruption and increased serum transaminase were frequent. Serious and newly detected side-effects after marketing were pseudomembranous colitis and melena, one case each. As for the oral administration of FOM-Ca to 83 patients hypertensive to beta-lactams, gastrointestinal side-effects were seen but none of them developed hypersensitivity, an allergic reaction. PMID- 8458681 TI - Hypotensive effects and influence on serum lipids of SQ29,852, a new angiotensin converting enzyme inhibitor, in patients with essential hypertension: a comparison with atenolol. AB - The effects of SQ29,852 (n = 24), a new angiotensin converting enzyme inhibitor, and atenolol (n = 22), monotherapies were compared in 46 patients with mild to moderate essential hypertension. Both SQ29,852 (mean dose 15.0 +/- 5.1 mg/day) and atenolol (mean dose 37.5 +/- 18.5 mg/day) significantly decreased both systolic and diastolic blood pressures. There were no significant changes in serum lipids, apolipoproteins, lipoproteins or atherosclerotic indices after both SQ29,852 and atenolol. There were also no significant inter-group differences. There were no serious side effects or abnormal laboratory tests in both treatment groups. It is concluded that SQ29,852 is an effective antihypertensive drug without adverse effect on lipid metabolism. PMID- 8458683 TI - Comparative bioavailability of two enteric-coated capsules of omeprazole in healthy volunteers. AB - A comparative bioavailability study was carried out on two enteric-coated capsules (20 mg each) of omeprazole (omeprazole, Alembic: "A" and Losec, Astra, England: "B"). The in-vitro dissolution of both products "A" and "B" met the prescribed USP standard. The bioavailability of single dose (20 mg) and multiple doses (20 mg once daily for 7 days) of both products "A" and "B" were carried out in eight healthy male volunteers in a crossover design. The rate and extent of bioavailability of omeprazole was higher in product "A" following a single oral dose, suggesting its therapeutic advantage over the product "B" in the prevention of acid aspiration during surgery. In multiple dose study, the two products were found bioequivalent as assessed by AUC0-infinity, Cmax, tmax and t1/2 elimination. PMID- 8458682 TI - Prescription drug use in lactating mothers: an experience at a referral hospital and in a community in India. AB - The aim of the study was to investigate the extent of prescription drugs administered for common disorders during the post partum period. This is a prospective survey of disorders and drug use in 1) immediate postpartum mothers (n = 200) admitted to the maternity wards, 2) in post-natal hospital follow-up clinic (n = 200) and in 3) the rural home based community (n = 100). A pretested questionnaire was filled in by medical officers after interviewing the mothers. The mean age of the mothers was 25 years and a literacy rate of 50% above the 10th grade. Over 80% of the women were multigravida in the entire sample; 45% underwent Caesarean Section in a hospital; 97.6% had a normal delivery in the community. In the hospital settings 4.1% infants had jaundice and 1% had congenital anomalies. In the community setting, diarrhoea and pneumonia was seen in 2.6% of the infants. Apart from the use of nutritional supplements, such as iron, calcium, multivitamins etc., most commonly prescribed drugs were analgesics (in 70% of patients in the hospital settings, 56% of the patients in the postnatal clinic and 37.6% patients in the community), and antibiotics (90% of the patients in the hospital settings, 86% of the patients in the postnatal clinic and 13% of the community based patients). Antihypertensives agents (2.5% of the patients), digoxin (1.5% of the patients), bronchodilators (1% of the patients) and sedatives (3.5% of the patients) were prescribed to admitted patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458684 TI - Partial synthesis of five new analogues of the peptido-lactone Virginiamycine S1, modified in the fifth and/or sixth position ([Xxx5]-VS1 with Xxx = Ala, Asp, Asn and Lys and [Ala5,Gly6]-VS1). AB - We achieved the reconstruction of VS1-analogues containing a substitute for the fifth residue, gamma-oxo-Pip (Pip = pipecolic acid), starting from VS1 pentapeptide (VS5P;3) the latter being prepared by a two-step degradation process of the native antibiotic VS1 (1a). Protecting groups during the procedure were chosen in order to realize a minimal number of steps. Most of these gave excellent yields, including final cyclization between the fourth and fifth residue. In total, four analogues were synthesized with Ala, Asp, Asn and Lys (1b) replacing gamma-oxo-Pip. Among these, [Lys5(Tfa salt)]-VS1 is water-soluble, which is an important characteristic for eventual application of VS1 as a pharmaceutical agent. In the proposed reaction sequence, we made sure that residues 4 (MePhe) and 6 (Phg) became partially epimerised. We therefore obtained each time after cyclization a total of four epimers that have been separated by preparative TLC. The chiral identity of the final residues was realized by GC (Chirasil Val-III) on the total hydrolysates. PMID- 8458685 TI - Comparative study of the stability of the folding intermediates of the calcium binding lysozymes. AB - Unfolding profiles of two calcium-binding lysozymes, equine milk lysozyme and pigeon egg-white lysozyme, were obtained by circular dichroism and proton NMR measurements. Equine lysozyme unfolds through a stable molten globule intermediate. The molten globule of equine lysozyme was characterized as more ordered than that of bovine alpha-lactalbumin. On the other hand, pigeon lysozyme unfolds by a two-state mechanism and the intermediate could not be observed in guanidine or thermal unfolding, the same as with conventional non-calcium-binding lysozymes. Thus, from the point of view of the unfolding profile, equine lysozyme belongs to the group of alpha-lactalbumin, but pigeon lysozyme belongs to the conventional lysozyme group. PMID- 8458686 TI - Linear tripeptide conformation. Crystal structures of Cbz-glycylglycyltyrosine methyl ester and Cbz-glycyl(D,L)tyrosylglycine ethyl ester. AB - The structures of two tripeptides, Cbz-glycylglycyltyrosine methyl ester (ZGGYOMe) and Cbz-glycyl(D,L)tyrosylglycine ethyl ester (ZGYGOEt) have been determined from single-crystal X-ray diffraction data. Crystals of ZGGYOMe are monoclinic, space group P2(1), with a = 12.427(3), b = 4.999(3), c = 17.401(6) A, beta = 99.98(2) degree and Z = 2. The final R-index is 0.049 for 1698 reflections with I > or = to 2 sigma (I). Crystals of ZGYGOEt are monoclinic, space group P2(1)/n with a = 12.134(8), b = 14.614(3), c = 26.154(9) A, beta = 98.78(4) degrees, Z = 8. The final R-index is 0.067 for 4457 reflections with I > or = to 2 sigma (I). Both peptides adopt highly extended structures; principal torsion angles are omega 0 = 175.0(4) degrees, phi 1 = 69.2(5) degrees, psi 1 = -154.9(4) degrees, omega 1 = -175.8(4) degrees, phi 2 = 165.4(4) degrees, psi 2 = 154.2(3) degrees, omega 2 = 169.6(3) degrees, phi 3 = -94.8(5) degrees, psi 3 = -47.6(5) degrees for ZGGYOMe and, for the two independent molecules of ZGYGOEt, omega 0 = 177.9(4) degrees, 178.9(4) degrees, phi 1 = -172.0(4) degrees, 169.7(4) degrees; psi 1 = 174.4(4) degrees, -162.5(4) degrees; omega 1 = -170.1(4) degrees, 176.7(4) degrees; phi 2 = -130.8(4) degrees, 130.3(5) degrees; psi 2 = 162.8(4) degrees, -163.3(4) degrees; omega 2 = -177.6(4) degrees, 176.2(4) degrees; phi 3 = -169.9(4) degrees, 172.9(4) degrees; psi 3 = -168.2(4) degrees, 160.9(4) degrees. The structures are of interest since the first one adopts a conformation unlike those of related GGX sequences and the latter shows an antiparallel hydrogen-bonding pattern. PMID- 8458687 TI - Synthesis of substrate analogues for trypanothione reductase. AB - The synthesis and chemical characterisation of a range of substrate analogues for trypanothione reductase are described, with the spermidine portion of trypanothione replaced by the 3-dimethylaminopropylamide moiety. Using 1 hydroxybenzotriazole/N-hydroxysuccinimide coupling, products were obtained which had a range of replacements of the gamma-glutamyl groups of the enzyme substrate. The materials were characterised by FPLC, 1H/13C NMR spectroscopy and FAB mass spectroscopy. PMID- 8458688 TI - Unusual cleavage of peptidic hormones generated by trypanosome enzymes released in infested rat serum. AB - Gonad and thyroid dysfunctions are often observed in human and experimental models during african trypanosomiasis. The enzymatic activity of components released by the trypanosomes towards peptide hormones (e.g. GnRH, TRH) have consequently been studied. The incubation products of GnRH by (i) healthy or infested rat serum: (ii) trypanosomal components released by using a specific procedure; (iii) infested and normal rat brain extracts have been analysed by RP HPLC fractionation. The peptide cleavage has been assessed by determination of either the amino acid compositions or relative molecular weight (by FAB mass spectrometry) of the different resolved HPLC fractions. Different protease inhibitors and a reducing agent have also been tested and a serine, cation sensitive, thiol-dependent endopeptidase activity has been predominantly identified to be released by the trypanosomes in host circulation. It has been shown that the peptidase activity(ies) is(are) able to: (i) degrade the peptide hormones (GnRH, TRH) considered as important neuromodulators and neurotransmitters; (ii) generate an unusual N-terminal tetrapeptide (GnRH1-4) appearing to be still active towards the gonadal hypothalamo-pituitary axis. PMID- 8458689 TI - Novel class of silicon-based protective groups for the side chain of tyrosine. AB - A novel class of silyl-based protective groups compatible with the Bpoc/t-Bu strategy has been developed for the side chain of tyrosine. Carbobenzyloxy (CBZ) and biphenylisopropyloxy (Bpoc)-O-beta-trimethylsilylethyl-tyrosine (10 and 12) and CBZ-O-beta-dimethylphenylsilylethyl-tyrosine 14 were prepared in reasonable yields and in very high purity. The trimethylsilylethyl (TMSE) group proved to be 3-4 times more stable than the tert-butyl ether group towards 0.5% TFA. The latter is removed up to 4% during the acidolysis of the Bpoc group. As expected, the dimethylphenylsilylethyl (DMPSE) group was even more resistant towards 0.5% TFA (five time greater than the TMSE analog). Both silyl protective groups were found to be resistant towards a variety of reagents used in peptide synthesis, such as trialkylamines, hydroxybenzotriazole, trialkylphosphine and nucleophiles. They are readily removed in neat TFA in 5-20 min in the absence of cation scavengers, without any detectable alkylation of the phenolic ring. The application of the new silyl-based protective group was demonstrated by the synthesis of the C-terminal 29 amino acid peptide of the basic pancreatic trypsin inhibitor by the prior thiol capture methodology. The protected octapeptide BocC(Acm)QT)(tBu)FVY(TMSE)GG-PO-dibenzofuranthiol++ + was synthesized by solid phase peptide synthesis using Bpoc-(O-TMSE)-Tyr-OH in greater than 90% yield and coupled to an unprotected 21-mer. The partially blocked, purified peptide was deprotected quantitatively in neat TFA in 1 h. PMID- 8458690 TI - Development of a radioimmunoassay for some agonists of growth hormone-releasing hormone. AB - A radioimmunoassay (RIA) method was developed for determination of superactive GH RH agonist Dat1,Ala15,Nle27 GH-RH(1-28)Agm29 (MZ-2-51) and some of the related analogs in biological fluids. The analogs were radioiodinated using the Bolton Hunter method. For the generation of antibodies, rabbits were immunized with MZ-2 51 and its C-terminal derivative Nle27 GH-RH(17-28)Agm29, conjugated to bovine serum albumin with glutaraldehyde. The resulting antibodies exhibited high affinity and very low cross-reactivity with related, naturally occurring peptides, enabling us to set up a sensitive and specific RIA. High cross reactions with some of the MZ-2-51 derivatives like MZ-3-149 (40%) and related compounds made it possible for us to also assay these analogs with the same antibody. At B/Bo of 23-37%, the final dilutions of the antibodies ranged from 1:35000 to 1:120000. The minimal detectable concentration of MZ-2-51 was 1.4 fmol (4.6 pg)/tube. The intra- and inter-assay variations were 2.2-4.1% and 9.3-13.9%, respectively. The antibody permitted direct determination of the analogs, without extraction, from biological fluids and tissue extracts. The analogs proved to be stable in serum, and no special treatment of sample was required. Pharmacodynamic studies were performed in rats. Serum levels of GH-RH(1-29) and two of its analogs were monitored following subcutaneous injection. Serum concentration of the analogs and GH-RH(1-29) reached a peak 15 min after injection and returned to basal levels within 90-120 min. Serum GH levels also reached a peak in 15 min, but declined more slowly in the case of analogs than GH-RH(1-29). The biological half-life of both analogs was significantly longer than that of GH-RH(1-29), probably due to their reduced enzymatic degradation. PMID- 8458691 TI - Peptide amidation by enzymatic transacylation and photolysis. AB - A series of model peptides with a C-terminal protected amide group were prepared by enzymatic transacylation. The protection groups were removed by photolysis to give the warranted peptide amides in high yields. Furthermore, fragments of human calcitonin were prepared. Various protective groups were employed, and the pH, solvent and concentration dependency of the enzymatic transcylation were examined. The photo-cleavage reaction was examined for wavelength, concentration and pH dependency. It was shown that the optimal yields required addition of a chemical scavenger for the photolysis byproducts. PMID- 8458692 TI - Synthesis and biological activities of psi (CH2NH) pseudopeptide analogues of the C-terminal hexapeptide of neurotensin. AB - Each peptide CO-NH function in the biologically important C-terminal 8-13 sequence of neurotensin was replaced by the reduced CH2-NH isostere using the rapid in situ solid phase procedure developed by Sasaki & Coy. In general this modification resulted in a drop in receptor affinity except for the [Arg psi(CH2NH) Arg]-NT8-13 analogue (PIC50 9.23 vs. NT8-13 pIC50 8.03). This analogue also showed enhanced enzymatic stability, but acted as a full agonist as shown by the observation of relaxations of guinea-pig colon ascendens. PMID- 8458693 TI - Multiple release of equimolar amounts of peptides from a polymeric carrier using orthogonal linkage-cleavage chemistry. PMID- 8458694 TI - Conformations of psi [CH2NH] pseudopeptides. Cyclo[Gly-Pro psi [CH2NH]Gly-D-Phe Pro]-TFA and cyclo[Gly-Pro psi [CH2NH]Gly-D-Phe-Pro]. AB - The cyclic pseudopentapeptide cyclo[Gly-Pro psi [CH2NH]Gly-D-Phe-Pro] and its TFA salt were synthesized by solution methods, and their conformations were studied by NMR spectroscopy in both DMSO-d6 and CDCl3. While intramolecular hydrogen bonding is observed with some conformers, the nature of the solvent and the presence of TFA affects the relative structural rigidities of the compounds. No evidence was found for the psi [CH2NH] or psi [CH2NH2+] units acting as H donors in this series. PMID- 8458695 TI - Synthesis of tetrapeptide p-nitroanilides catalyzed by pepsin. AB - Swine pepsin at pH 5 efficiently catalyzes a condensation between Z-Ala-Ala-Phe OH and p-nitroanilides of Leu, Phe, Val, Ala and Arg that leads to formation of corresponding benzyloxycarbonyl-tetrapeptide p-nitroanilides with yields of 70 90%. These reactions are complicated by co-precipitation of pepsin and the reaction products that necessitates the use of a relatively high concentration of pepsin. PMID- 8458696 TI - Managing the integration of technologies. Development of the immunoassay. AB - Many factors, including cultural, economic, technical, and regulatory influences, affect how different technologies come together for today's medical diagnostic products. An analysis of the development of automated immunoassay systems reveals that companies used a variety of approaches to access needed technologies, that mature technologies play an important role in the development of new products, and that implementation seemed more important in these companies than strategy. PMID- 8458697 TI - Pharmaceutical innovation in the United States. Factors affecting future performance. AB - Fueled by high returns on its investments, the pharmaceutical industry in the United States has flourished for the past 50 years. The regulatory strategy of demanding stringent testing then allowing market-based pricing has allowed private companies to fund ambitious research and development activities with the assurance that these investments will be recovered. However, aggressive managed care cost-containment strategies threaten the companies' ability to recoup research and development expenses and may affect their willingness to invest in future innovative research. PMID- 8458698 TI - Demand as a driving force in medical innovation. AB - On the basis of two case histories of medical device innovation, two aspects of demand are identified: (a) the prospect of new markets and (b) information about user needs. Conditions for direct interaction between the user and producer in the innovation process are identified. The article concludes with some normative implications for the publicly designed generation of new medical technology. PMID- 8458699 TI - Problems with toxicity studies in the assessment of new drugs. AB - The development of new medicines requires a lot of time and the efforts of many researchers. One of the most taxing parts of this endeavor is the need for long term toxicity studies in different animals. This paper describes the development of two different medicines: zimeldine, an antidepressant, and omeprazole, a compound that acts against a specific enzyme in the gastric mucosa that is necessary for the production of gastric acid. Zimeldine was launched in the international market but had to be withdrawn when it caused severe unexpected adverse reactions. Omeprazole has been marketed successfully after a prolonged development phase characterized by difficult problems with the toxicity studies. Against the background of these two descriptions, this article questions the rationale for the present rules for long-term toxicity studies and emphasizes the need for leaders in the pharmaceutical industry to have a solid scientific background in order to be able to decide whether to abandon a project. PMID- 8458700 TI - The pulmonary artery (Swan-Ganz) catheter. Evaluation of a hemodynamic monitoring device in critical care medicine. AB - The pulmonary artery catheter (PAC) is an invasive hemodynamic monitoring device that is used extensively in critical care units. This technological advance allows the critical care physician and nurse to closely monitor physiological functions at the bedside. There have been no formal evaluations of the impact of this device on patient care. Reviews and observational studies have yielded different conclusions regarding risks and benefits to patients. This has resulted in much editorial comment expressing divergent opinions on the value of the PAC, but there has been no scientific evidence to guide practice and no apparent effect on the use of these devices. The PAC and other medical monitoring devices must be evaluated with respect to their impact on patient care. PMID- 8458701 TI - The development of contraceptive technology. Case studies of incentives and disincentives to innovation. AB - This paper examines the characteristics of the process of innovation as applied to a range of contraceptive technologies. Whereas the understanding of how and why innovation works or does not work has grown in the past few decades in such professional fields as electronics, aviation, and optics, only the first attempts are currently under way in medicine. Borrowing from other fields, this paper proposes a theoretical underpinning to the process of innovation as it would apply to the development of medical technology. Subsequently, it documents this process with regard to contraceptive technology (oral contraceptives, injectables, intrauterine devices, implants, and surgical contraception), providing a framework of first-, second-, and third-generation definitions of development. A number of observations about the importance of certain supply- and demand-side determinants of the direction and rate of medical innovation conclude the essay. PMID- 8458702 TI - Technology transfer to developing countries. Lessons from Colombia. AB - Medical technology will contribute to improving the health status of people in developing countries only when it is carefully implemented after proper planning. Providers, users, health ministry employees, and industry all share responsibility for proper planning and careful implementation. PMID- 8458703 TI - Methodology of OTA's report on drug labeling in developing countries. AB - This article discusses the methodology of the OTA Project on Drug Labeling in Developing Countries. This report describes (a) the process of the project; (b) observations from a field visit to Thailand; (c) the development of the multinational pharmaceutical industry; and (d) influences on multinational pharmaceutical companies from their home countries, host countries, international organizations, self-regulation, and public interest groups. The results of the assessment will appear in the final report to Congress. PMID- 8458704 TI - How important is the scientific literature in guiding clinical decisions? The case of magnetic resonance imaging. AB - Little is known about how information diffuses to clinicians and influences their purchase and use of new technology. This is especially true about the role of the scientific literature. As a case study, we examined the literature for magnetic resonance imaging (MRI) during the years preceding and the first five years following its clinical introduction. Using a computerized retrieval system, we identified approximately 1,700 citations in which MRI was the major topic. The clinical literature on MRI was heavily concentrated in radiology journals. Less than 28% of articles compared MRI with alternative diagnostic technologies. During the first five years of clinical availability, the diffusion patterns of scientific articles and operational units mirrored the example set by computerized tomography (CT), in that a substantial number of units were purchased in both research and nonresearch settings before studies were available comparing them to alternative diagnostic technologies. These patterns of diffusion, combined with other studies of the MRI literature's content and methodology, suggest that less comprehensive and objective sources of information were important in early purchasing decisions. This study also suggests that the present readership and publication patterns of professional journals may not facilitate effective, rapid information dissemination about innovations to a broad spectrum of clinicians. PMID- 8458705 TI - Economic assessment of magnetic resonance imaging for inpatients: is it still too early? AB - This economic assessment of the implementation of magnetic resonance imaging (MRI) in a French hospital examines data on the diagnostic resources used in neurology and neurosurgery before and after MRI was available. Given a similar patient population and case mix, there was no change in the resources used other than the addition of MRI. So far, MRI appears to be a complement to, and not a substitute for, other imaging techniques used in neuroradiology. The focus of this work is purely economic; its conclusions do not challenge the major scientific contributions of MRI. PMID- 8458706 TI - Quality assurance procedures in radiotherapy. Economic criteria to support decision making. AB - This paper details the costs of two types of quality assurance activities in radiotherapy: in vivo dosimetry, intended to check the delivered dose, and portal imaging to check the treated volume. For both activities, either on-line or off line techniques may be used. Describing the costs allows the calculation of which techniques are most cost-efficient for different radiotherapy departments. PMID- 8458707 TI - Carotid endarterectomy for asymptomatic patients. Assessing results of a quantitative synthesis. AB - Carotid endarterectomy (CE) surgery for asymptomatic patients remains controversial despite hundreds of published studies and recent randomized trials. Safety and efficacy are assessed using a quantitative synthesis method derived from meta-analysis and a "critical multiplist" inference approach. In addition, multivariate analyses reveal that use of a surgical shunt could further improve CE outcomes. Methods are examined for both their "confirmatory" and "exploratory" value. PMID- 8458708 TI - Geographic variation in the treatment of prostate cancer in Connecticut. AB - In Connecticut there was considerable variation by town of residence in the proportions of patients diagnosed in 1985-1988 receiving transurethral resection only, prostatectomy, and irradiation (without surgery) for local-stage prostate cancer and receiving endocrine surgery for late-stage prostate cancer. Age and socioeconomic variables were examined as predictors of this variation. PMID- 8458709 TI - Report from the Canadian Coordinating Office of Health Technology Assessment (CCOHTA). Satellite symposium to the eighth annual meeting of the International Society of Technology Assessment in Health Care (ISTAHC). PMID- 8458710 TI - Immunomodulation with soluble IFN-gamma receptor: preliminary study. AB - Several in vivo experiments support the hypothesis that an IFN-gamma antagonist may have therapeutic applications in autoimmune diseases, hypersensitivities, and alloreactions. IFN-gamma exerts its biological activity through the binding to a single-chain cell surface receptor. The protein that corresponds to the external domain of mouse IFN-gamma receptor was expressed in insect cells infected with recombinant baculovirus; this protein was characterized and used in vivo as a prototype of the IFN-gamma antagonist. This protein does not show any strong antigenicity after in vivo injection in mice. Despite a blood half-life of only 1 3 hr as demonstrated in pharmacokinetic experiments, the mouse soluble IFN-gamma R was able to modify the onset of acute GVHD (alloreaction) and chronic GVHD (lupuslike disease). PMID- 8458711 TI - Tumor necrosis factor/cachectin as an effector of T cell-dependent immunopathology. PMID- 8458712 TI - Immune-mediated injury in bacterial meningitis. AB - Cytokines are involved in the host response to bacterial infections. In bacterial meningitis, intrathecal synthesis of TNF-alpha and IL-1 is likely to contribute to CNS injury by recruitment and activation of inflammatory cells with subsequent release of toxic factors, such as reactive oxygen intermediates and excitatory amino acids (glutamate), leading to neuronal cell death with neurologic sequelae. In rats with experimental meningitis, pretreatment with TGF-beta inhibits cerebrovascular changes and brain edema formation in the early, TNF-alpha independent phase. Provided its local production in bacterial infection, TGF-beta may comprise a host factor interfering with immune pathologic events altering the integrity of the endothelial barrier. PMID- 8458713 TI - Clinical experiences with interferon-alpha and interferon-gamma. PMID- 8458714 TI - Clinical experience with Escherichia coli rHuGM-CSF. AB - The use of rHuGM-CSF has resulted in patient benefit as shown by reduced infections (MDS and AA), reduced days in intensive care (ABM transplant), better adherence to cancer chemotherapy protocols, and the ability to use full doses of antiviral drugs in AIDS and cytomegalovirus retinitis. The adverse reactions are significant when high doses are used, therefore high doses should be avoided (there is a plateau in the dose-effective biological responses). At recommended doses, GM-CSF is well tolerated and is a valuable adjunctive therapy in the management of patients with conditions of dysmyelopoiesis and myeloid hypoplasia associated with myelotoxic therapy, or after bone marrow transplantation. PMID- 8458715 TI - In vitro and in vivo activity and pathophysiology of human interleukin-8 and related peptides. AB - Interleukin-8 is a member of a novel cytokine family and has been found to be an activator and attractant for human neutrophils in vitro. The in vivo activity was tested in experimental animal models by intradermal and intravenous administration of IL-8. Intradermal administration of human IL-8 in rats induces a rapid and concentration-dependent neutrophil infiltration, which peaks 4 hr after IL-8 application. Injection of GRO-alpha induces a similar chemotactic response, whereas neutrophil-activating peptide-2 was significantly less active. When injected intravenously into rabbits, IL-8 induced neutrophil sequestration in the lungs and, following repeated injections, caused septal and intraalveolar edema and lung damage resembling that seen in adult respiratory distress syndrome. The fact that IL-8 is induced and secreted from many different cell types suggests its involvement in a variety of physiologic and pathologic conditions as a neutrophil chemoattractant and, possibly, as an activator of other neutrophil responses. PMID- 8458716 TI - Pathology induced by inflammatory cytokines. Introduction. PMID- 8458717 TI - Pathology of recombinant human transforming growth factor-beta 1 in rats and rabbits. AB - The systemic administration of high doses of rHuTGF-beta 1 to rats produced a spectrum of lesions in multiple target tissues, including liver, bone, kidney, heart, thymus, pancreas, stomach, cecum, at the injection vein, and in skeletal muscle at the site of anesthetic injection. The majority of these lesions can be attributed to known biological activities of TGF-beta 1. High-dose dermal application resulted in local effects at the wound sites without systemic toxicity. PMID- 8458718 TI - Pathology induced by leukemia inhibitory factor. AB - Leukemia inhibitory factor is a glycoprotein growth and differentiation factor with pleiotropic activity. LIF has potent effects on the hematopoietic system, including megakaryocyte progenitor cells. In addition, LIF has bone regeneration activity, induces cachexia and acute-phase response in hepatocytes, and inhibits adipogenesis, to mention the more important activities. In vivo LIF treatment in monkeys and rodents was followed by signs of general toxicity, cachexia, acute phase reaction, and stimulation of hematopoiesis. The safety margin for possible therapeutic effects on hematopoiesis seems to be very narrow. PMID- 8458719 TI - Pathophysiologic alterations induced by tumor necrosis factor. AB - Work from several laboratories has documented that TNF is toxic in vivo. The data are sufficiently compelling that there is little doubt that this small peptide mediator can induce altered pathophysiology and tissue damage if injected in large quantities. Whereas injection of high-dose, exogenous rHu-TNF results in toxicity, and the production of very high levels in lethal septic shock is detrimental, the exact role of this molecule in inflammation is yet to be defined completely. At low, physiologic levels, TNF may be a necessary component required to orchestrate an effective immune response to a successful resolution. Several works have shown that inhibition of TNF with specific antibodies in models of bacterial infection can decrease survival (Havell, 1987; Echtenacher et al., 1990). Clearly, further work must be done to resolve the issue of the exact role of TNF in organ injury during septic shock. PMID- 8458720 TI - Comparative pathology of recombinant murine interferon-gamma in mice and recombinant human interferon-gamma in cynomolgus monkeys. AB - Interferon-gamma is a highly species-specific cytokine and has the most restricted host range of activity of the interferons. Recombinant human IFN-gamma was one of the first species-specific recombinant proteins to be thoroughly assessed in conventional safety models used for xenobiotics. Acute single-dose intravenous toxicity studies with rHuIFN-gamma were performed in rats, marmosets, and squirrel monkeys with no indications of toxicity. A complete series of subchronic toxicity studies and segment I and II reproductive studies in the rat revealed no evidence of toxicity at any of the doses tested. These results suggested that studies conducted in pharmacologically nonresponsive species may not be predictive of clinical toxicity. Human IFN-gamma is active on nonhuman primate cells, though not at the same level as on human cells. Multidose studies in cynomolgus monkeys with rHuIFN-gamma for 28 or 90 days were predictive of many of the dose-limiting clinical toxicities. Qualitative similarity was observed between toxicity studies employing rHuIFN-gamma in the cynomolgus monkey and rMuIFN-gamma in the mouse. The adverse effects seen in toxicity studies with cytokines and growth factors are often exaggerated pharmacological effects of the molecules, and therefore can only be studied in a responsive species. In situations in which a high degree of species specificity is encountered, studies employing a recombinant protein in a homologous species may provide a useful test system for preclinical safety assessment. PMID- 8458721 TI - CT or not CT?--that is the question. PMID- 8458722 TI - Comprehensive inpatient treatment for intractable migraine: a prospective long term outcome study. AB - This paper describes outcome data for 100 patients with severe, intractable, persistent migraine (chronic daily headache), who were admitted to a comprehensive inpatient Head-Pain Treatment Unit for a mean of 8.5 days. Headache, pain-related behavior, depression, sleep disturbance, functional performance, work status, and medication use were assessed at admission, post discharge (mean = 2.3 weeks) and long-term follow-up (mean = 8.3 months). Significant improvement noted two weeks after discharge was maintained over time. Long-term results revealed a 64% reduction in the mean number of days in a 2-week period with severe to incapacitating headache (6.29 to 2.26), with a corresponding increase in pain-free days (1.03 to 5.40). At follow-up, the frequency of severe headaches was reduced by at least 50% for 75% of the patients. The mean rating of overall improvement was 74%. Patients on work-leave due to pain dropped from 24% to 4%, while the number of working patients rose from 31% to 53%. The data showed statistically significant reductions in days lost to pain, depression, sleep disturbance, and use of symptomatic medication. All the above analyses were significant at P = .000. These results demonstrate the efficacy of the inpatient headache program intervention for this group of patients. PMID- 8458723 TI - Autonomic function testing in patients with tension-type headache. AB - Autonomic nervous system function was studied in 51 patients with tension-type headache. The Valsalva manoeuvre, deep breathing test, sustained handgrip test, orthostatic test and spectral analysis of heart rate variability in the supine and standing positions were performed in a group of 51 patients of both sexes aged 21 to 50 years and in an age-matched control group of 45 healthy volunteers. Diastolic blood pressure increase and particularly heart rate increase during sustained handgrip were significantly reduced in the headache group, when compared to the control group, while the results of the remaining tests did not significantly differ between the control and headache groups. No significant differences were found between the episodic (19 patients) and chronic (32 patients) tension-type headache subgroups. It is concluded that sympathetic function is impaired in tension-type headache patients. PMID- 8458724 TI - Failure to mourn as a possible contributory factor to headache onset in adolescence. AB - Patients who have suffered from chronic headaches frequently are unable to identify a triggering physical or emotional event that precipitated the headache process. This study examined the headache histories of teenage headache patients, the majority of whom were found to be depressed, and found that personal loss occurred within 12 months of headache onset in 11 of 15 cases. Among the losses that were identified were those involving terminal illness and death of family members, separation and/or divorce in the family, or change of residence from a familiar area. It is recommended that opportunities for dealing with feelings about their losses should be presented to patients, whether or not the patients express a need for this. Furthermore, it is recommended that patients of any age who cannot identify a triggering event prior to the onset of their headache histories should be questioned in detail about the possible correlation with personal loss. PMID- 8458725 TI - Suggestibility and headache reports in schoolchildren: a problem in epidemiology. AB - In a sample from the general population of school children of 15 years of age, we studied whether receiving information about the prevalence of headaches had any effect on their subsequent headache report. Sixty children in the fourth year at four secondary schools were allocated at random to two conditions: a biased condition emphasizing the high prevalence of headaches and a neutral condition. Subjects in the biased condition reported more headaches but they did not report more other physical symptoms than the subjects in the neutral condition. The results are discussed in terms of Pennebaker's theory on reporting symptoms. It is concluded that epidemiological research using the general population should deal more explicitly with the way in which subjects are motivated to participate. PMID- 8458726 TI - Sometimes Jello helps: perceptions of headache etiology, triggers and treatment in literature. AB - Throughout history writers have attempted to describe the symptoms and evoke the misery of "a dismal headache." Writers from Plato to Stephen King have used the phenomenology of headache to illustrate their work. Lewis Carroll, for example, vividly describes the central scotoma, tunnel vision, phono-phobia, vertigo, distortions in body image, dementia and visual hallucinations that often accompany migraine. Although many authors have discussed the topic seriously, others have addressed the issue in a dismissive and even contemptuous manner, relegating this very real disorder to the status of a medical stepchild. We will examine headache etiology, triggers and treatment and explore the attitudes toward headache and headache sufferers found in literature. We have recently seen a growing understanding of the physiological basis of headaches. However, this knowledge has not yet reached the level of literature or popular culture. In an age when it seems every Sunday night brings a new "disease of the week" movie, and every human ill is subjected to often intense and numbing scrutiny by the media, the anguish of a chronic migraine sufferer will probably remain unexplored -unless she kills her husband and children during an attack. PMID- 8458727 TI - Computed tomography in the headache patient: is routine evaluation really necessary? AB - OBJECTIVE: To determine the likelihood ratio of a positive computed tomogram of the brain in the routine evaluation of headache patients. DESIGN: Consecutive patients with a chief complaint of headache were prospectively evaluated with computed tomography of the brain. Patients with headaches complicating other clinical disorders such as trauma, postictal state or known intracranial neoplasm were excluded. SETTING: Military tertiary care center. PATIENTS: Consecutive sample of 350 patients with a chief complaint of headache, regardless of the presence or absence of physical or neurologic signs, were referred for computed tomography of the brain. The patients were referred from a variety of inpatient and outpatient settings. RESULTS: Seven (2%) of the 350 patients had computed tomographic findings that were clinically significant. An additional 25 (7%) had positive computed tomographic findings, which were clinically insignificant for findings. All of the patients with significant computed tomographic findings had an abnormal physical or neurologic exam or unusual clinical symptoms. CONCLUSION: Routine computed tomography of the brain in headache patients with normal physical and neurologic exams and no unusual clinical symptoms has a low likelihood ratio for discovering significant intracranial disease. PMID- 8458728 TI - Focal headache during balloon inflation in the vertebral and basilar arteries. AB - BACKGROUND AND PURPOSE: Headache may be seen in acute cerebrovascular disease. The significance of localized headache in association with vertebrobasilar disease has not been recognized. SUMMARY OF REPORT: We describe a patient with a cerebellar arteriovenous malformation who underwent intravascular balloon occlusion of the vertebral and basilar artery. He developed reproducible patterns of referred pain with balloon inflation at specific sites. CONCLUSIONS: Well localized head pain in the setting of acute stroke should alert physicians to the possibility of localized arterial injury. The pattern seen in this patient has been documented in experimental situations, and should be of use in the setting of acute stroke. PMID- 8458729 TI - Roentgenographic findings of the cervical spine in tension-type headache. AB - Roentgenographic studies were carried out on 372 patients with tension-type headache and 225 normal control subjects to determine relationships between straightened cervical spines, low-set shoulders, and cervical spine instability. A great majority of the patients with tension-type headache were found also to have straightened cervical spine. Patients with tension-type headache may have a restricted progression of the cervical spinal lordosis, which results in a straightened cervical spine. The flexor muscles of the head and neck prevent physiological lordosis of the cervical spine, and their sustained chronic contraction may be a principal cause of a straightened neck. The low-set shoulder was frequently seen in patients with tension-type headache, and it may result in traction of the brachial plexus, which gives rise to pain in the neck and shoulders. Cervical spine instability, on the other hand, was rather infrequent in patients with tension-type headache. Its relationship to tension-type headache is unclear and warrants further study. Our results suggest that both a straightened cervical spine and low-set shoulders may play an important role in the pathogenesis of tension-type headache and its accessory symptoms. PMID- 8458730 TI - Respiratory sinus arrhythmia in cluster headache syndrome. AB - Respiratory sinus arrhythmia is regarded as indicative of cardiac vagal integrity. A ratio of the longest R-R interval to the shortest R-R interval during deep breathing test (E:I ratio) was calculated in controls (n = 49), cluster headache (n = 33) and CPH (n = 4) patients. E:I ratio decreased with age but was not dependent upon sex or upon smoking habits. Furthermore, there were no significant differences as regards E:I ratio between cluster headache patients in and outside a bout, or between patients with right-sided and left-sided headaches. However, the E:I ratio was found to be significantly lower in the cluster headache group as such, when compared with controls, but the number of patients disclosing pathological or borderline results was small, 2 and 2, respectively. This may indicate that a putative vagal dysfunction in cluster headache is usually less marked than in patients with e.g. diabetic autonomic neuropathy. Significant attack-related changes in the E:I ratio were detected in all individual patients though these changes were not of a uniform nature from individual to individual. E:I ratios were rather high in 3 out of 4 CPH patients examined. However, the number of patients in this group is too small to allow definite statements about the difference between CPH and cluster headache with regard to E:I ratios. There was no significant difference between E:I ratios outside and during a mild, short, mechanically precipitated attack in a single CPH patient. PMID- 8458731 TI - Variation in genetic identity within kinships. AB - Genetic identity, which may be important for kin recognition, is the fraction of the genome that is identical by descent. It is, except for the parent-offspring relation, governed by probability and its variance depends on the number of segregating units during meiosis. Using the recombination index as an approximation of this number the variance for genetic identity has been estimated for different kinds of kinship. PMID- 8458732 TI - A diallel analysis of gregarious oviposition in Drosophila melanogaster. AB - Drosophila females exhibit gregarious oviposition. This behaviour was analysed by a diallel cross. The trait shows considerable additive genetic variation and a significant dominant effect. A variance and covariance analysis suggests that ebony and taxi strains contain the most dominant alleles. Some maternal effect may also be present. This genetical architecture is in line with previous studies of selection and hybridization of the lines selected for high and low gregarious oviposition in Drosophila melanogaster females. PMID- 8458733 TI - MHC class II haplotypes and linkage disequilibrium in primates. AB - The loci encoding the major histocompatibility class II cell surface antigens DR, DQ, and DP exhibit a remarkable degree of allelic polymorphism. Strong linkage disequilibrium is also found between these loci in the human population. To study the evolutionary conservation of this disequilibrium the DQA1, DQB1, and DRB1-6 loci were analyzed in chimpanzee and gorilla by sequencing or/and oligonucleotide hybridization of PCR-amplified DNA. This analysis revealed several new DRB sequences. The distribution of DRB loci differs between human and nonhuman primate haplotypes, and the strong disequilibrium found on human haplotypes between alleles at DQA1 and DQB1 as well as between the DQ loci and the DRB1 locus was not detected in the nonhuman hominoids. Extensive recombination within and between the DR and DQ region appears to have occurred during the 3-7 million years since the divergence of the three species, resulting in little similarity of haplotypes between species. The strong disequilibrium found in the human species between these loci may either reflect haplotype-specific barriers to recombination, recent founder effects in the evolution of humans, or selection for specific haplotypes. PMID- 8458734 TI - Characterization of T cells expressing the gamma/delta antigen receptor in human renal allografts. AB - To investigate the role of gamma/delta+ T cells in allograft rejection, we have studied the TCR phenotype and function of lymphocytes infiltrating rejecting, rejected, and nonrejecting human renal allografts. Two-color immunohistologic staining showed that 19% of rejecting biopsies and 40% of rejected nephrectomies had significant infiltration (> 10% of the total T-cell population) with gamma/delta+ T cells. No biopsies from nonrejecting kidneys showed > 10% gamma/delta+ T cells. Flow-cytometry analysis of T-cell populations expanded from rejecting and rejected allografts demonstrated that 33% of biopsy- and 40% of nephrectomy-derived populations had significant percentages (> 10%) of gamma/delta+ T cells. Six cell lines with increased numbers of gamma/delta+ T cells were tested for cytolytic activity against the NK target cell line K562 and compared with cytotoxic activity of exclusively alpha/beta T-cell populations. Lysis was noted by all gamma/delta+, but no gamma/delta-, populations. To confirm that the cytotoxicity of these gamma/delta+ T-cell populations was not MHC directed, one nephrectomy-derived population with 69% gamma/delta+ T cells by cytometry and > 50% by immunohistology was studied extensively. High levels of killing were seen against the NK targets K562 and Daudi as well as other malignant, benign, and third-party renal cell lines, but relevant alloantigen expressing targets were not killed. Sterile cell sorting was used to isolate the gamma/delta+ T cells. The gamma/delta+ cells displayed enhanced killing of K562 while the gamma/delta- cells showed no cytolytic activity. Cytotoxicity mediated by gamma/delta+ T cells was also demonstrated against donor-derived, untransformed renal cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458735 TI - Selection of an unrelated donor for marrow transplantation facilitated by the molecular characterization of a novel HLA-A allele. AB - Precise HLA typing is crucial in the selection of marrow donors for the treatment of patients with hematologic malignancy. This study was undertaken to characterize an unusual variant of HLA-A30, designated HLA-A30JS, identified in a patient with leukemia who was a candidate for unrelated donor marrow transplantation. IEF and cDNA-sequencing analyses revealed that A30JS is a novel variant differing from the IEF-defined subtype A30.1 (encoded by the A*3002 allele) by a single amino acid substitution. An unrelated marrow donor was identified who was matched with the patient for HLA-A3, B7, B18, DR2, and DR3, but mismatched within the A30 antigen family for the two distinct alleles A*3002 versus A30JS. These two alleles encode a single amino acid substitution, Arg versus Gly, at position 56 in the alpha 1 domain. Position 56 is located outside the antigen-binding cleft of the class I molecule, suggesting that this substitution may not be functionally significant. Transplantation from this donor was performed and the patient is surviving free of leukemia for more than 700 days after transplant. The maximum acute GVHD observed was scored as grade II, but immunosuppressive therapy is still required for control of chronic GVHD. This study demonstrates how the molecular characterization of a novel HLA-A allele in a patient could facilitate the selection of an unrelated donor. Lacking this information, it would not have been possible to select a donor for this patient, and thus apparently successful marrow transplant could not have occurred. PMID- 8458736 TI - Polymorphism in the promoter region of HLA-DRB genes. AB - Polymorphism is a hallmark of the molecules encoded within the MHC of humans and other mammals. Recently, evidence of polymorphism has also been shown to exist in the transcriptional regulatory regions of HLA-DQB genes. In this article, we report that polymorphism exists also in the promoter region of HLA-DRB genes. The sequence of the regulatory region of DRB genes from five homozygous DR B-cell lines, each of a distinct DR haplotype, revealed a number of differences, some of which are in the critical class II boxes that are generally conserved in class II promoters. The major differences occurred in a comparison of DR4 to the other DR haplotypes. These data suggest the existence of another important source of HLA class II polymorphism that may play a role in susceptibility to HLA-associated autoimmune disease. PMID- 8458737 TI - Characterization of a novel gene (NKG7) on human chromosome 19 that is expressed in natural killer cells and T cells. AB - NKG7 is a cDNA clone generated from a human NK-cell clone. The DNA and predicted aa sequence of NKG7 is not homologous with any previously reported genes or peptides. NKG7 mRNA is expressed in activated T cells and in A-LAK cells isolated from the peripheral blood of normal individuals, and in normal human kidney, liver, lung and pancreas. Furthermore, NKG7 mRNA is expressed at high levels in TCR gamma delta-expressing CTL clones, and in some TCR alpha beta-expressing CTL clones (both CD4+ and CD8+), but is not expressed in other TCR alpha beta expressing CTL clones and in cell lines representing B cells, monocytes, and myeloid cells. NKG7 mRNA is not expressed in normal human brain, heart, or skeletal muscle. Southern hybridization of NKG7 suggests that NKG7 is a single copy gene localized to chromosome 19. A hydropathicity profile of the predicted 148 aa polypeptide indicates that NKG7 is a type-I integral membrane protein with a 38-aa extracellular domain and a 61-aa cytoplasmic domain. These results indicate that the NKG7 gene encodes a novel cell surface protein expressed in several cell types, including NK cells and T cells. PMID- 8458738 TI - [International Breast Feeding week, 1-7 August]. PMID- 8458739 TI - [Planning of Midwives' Day 1992]. PMID- 8458740 TI - [Variations in obstetric interventions among various midwives]. PMID- 8458741 TI - [Description of alternative birthing centers--Sahlgren Hospital in Goteborg]. PMID- 8458742 TI - [Continuity in infant nutrition]. PMID- 8458743 TI - The intensitive DL of tones: dependence of signal/masker ratio on tone level and on spectrum of added noise. AB - In Greenwood [J. Acoust. Soc. Am. 33, 484-502 (1961a)] the ratio of masked signal threshold to masker level (S/M) decreased about 4 dB at a masker level of about 50 dB SL, the 'transition' level, when noise bands were subcritical but not when supercritical. Schlauch et al. [J. Acoust. Soc. Am. 71, S73 (1982)] report a related result. A pilot study [Greenwood, Harvard Psychoacoustic Lab. Status Report 37, 8-9 (1961)] in which pure tones masked identical tones in-phase showed a larger change in S/M. Detailed tone-tone growth-of-masking curves from over a dozen subjects in 1967-69, and in 1960, are reported here. A transition in slope, of variable abruptness, often begins to occur at about 50 dB SL, dropping S/M ratio by 6 to 8 dB or more [Rabinowitz et al., J. Acoust. Soc. Am. 35, 1053 (1976)]; the curves sometimes possess two segments, sometimes are simply convex. All have overall slopes less than 1.0, known also as the 'near miss'. Consistent with other results [Zwicker, Acustica 6, 365-396 (1956); Viemeister, J. Acoust. Soc. Am. 51, 1265-1296 (1972); Moore and Raab, J. Acoust. Soc. Am. 55, 1049-1060 (1974)], addition of low-level wide-band and high-pass noise was found to counteract the change in S/M, i.e., to raise the high-level section of the growth of-masking curve. However, the ability of narrow 'band-pass' noise to exert this effect was greatest when added at a frequency ratio (band/masking-tone) of 1.3 to 1.5, which seems more closely to link the effects of added noise to the effects of increasing a masking band from sub- to supercritical width (above). Interpretation of the decrease in DL with level begins by noting that the 'transition' level correlates approximately with the level at which a primary unit population excited by a given pure tone begins rapidly to expand basally. Underlying this, the basalward shift of a tone's displacement envelope peak accelerates at about the same level [Rhode, J. Acoust. Soc. Am. 49, 1218-1231 (1971); Sellick et al., J. Acoust. Soc. Am. 72, 131-141 (1982)].(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8458744 TI - The mismatch negativity cortical evoked potential elicited by speech in cochlear implant users. AB - The mismatch negativity (MMN) event-related potential is a non-task related neurophysiologic index of auditory discrimination. The MMN was elicited in eight cochlear implant recipients by the synthesized speech stimulus pair /da/ and /ta/. The response was remarkably similar to the MMN measured in normal-hearing individuals to the same stimuli. The results suggest that the central auditory system can process certain aspects of speech consistently, independent of whether the stimuli are processed through a normal cochlea or mediated by a cochlear prosthesis. The MMN shows promise as a measure for the objective evaluation of cochlear-implant function, and for the study of central neurophysiological processes underlying speech perception. PMID- 8458745 TI - Genetics of age-related hearing loss in mice: I. Inbred and F1 hybrid strains. AB - The auditory-evoked brainstem response (ABR) was used to assess hearing loss in five inbred strains of mice and all ten combinations of F1 hybrids. The inbred strains are CBA/H-T6J (CH), DBA/2J (D2), C57BL/6J (B6), BALB/cByJ (BY) and WB/ReJ (WB). The F1 hybrids are CHD2, CHB6, CHBY, CHWB, D2B6, D2BY, D2WB, B6BY, B6WB, and BYWB. At middle age (12, 16 months), mice were tested with click stimuli. At a relatively old age (23 months, near inbreds' median life span), they were tested with both click and tone-pip stimuli. The CH mice and their four F1 hybrid strains exhibit lower thresholds than the other strains, with the F1 strains being most sensitive (i.e., hybrid vigor). The D2 inbred and the three D2 F1 hybrids (excluding CHD2) exhibit the earliest and most severe hearing losses. The B6, BY and WB inbred strains exhibit severe hearing losses between 16 and 23 months of age; however, the B6BY, B6WB and BYWB F1 hybrids have significantly lower thresholds than their parental strains (genetic complementation). These data support a genetic model for recessive alleles at three different loci which contribute to age-related hearing loss. The CH mice have none of the recessive alleles, and the D2 mice are homozygous recessive for all three; the B6, BY and WB inbred strains are homozygous recessive respectively for one of the three loci. PMID- 8458746 TI - Zebrafish inner ear sensory surfaces are similar to those in goldfish. AB - The inner ear of the zebrafish (Brachydanio rerio) is very similar to that of the goldfish in its structural details, including the distribution and orientation of mechanosensory hair cell populations. Both species have been used in studying different aspects of the acoustic startle response. These structural similarities suggest that the zebrafish is a valid representative model for understanding peripheral hearing specializations in otophysan fishes. PMID- 8458747 TI - Turn-specific differences in the endocochlear potential between albino and pigmented guinea pigs. AB - Recent findings indicate that structural differences exist in the stria vascularis (SV) between albino and pigmented guinea pigs. In the higher cochlear turns, volume density for marginal cells in the albino SV is abnormally large, while that for intermediate cells (melanocytes) is abnormally small. These anatomical variations suggest that functional differences between albino and pigmented inner ears also may be found. To examine this possibility, four strains of guinea pigs were studied, consisting of Hartley albino (N = 9) and NIH outbred pigmented (N = 15) guinea pigs, as well as albino (N = 11) and pigmented (N = 15) guinea pig siblings born to mixed litters. Tracheotomy and carotid artery cannulation were performed. Animals were mechanically ventilated, with periodic samples drawn for arterial blood gas analysis. Blood pressure, heart rate and rectal temperature were monitored. Compound action potentials were measured first to assess cochlear viability. Positive endocochlear potentials (+EP) then were recorded, beginning with the fourth turn, followed by the first, second and third turns. Results showed that the +EP in albinos remained relatively constant across cochlear turns, but decreased significantly from base to apex in the pigmented inner ears. Across all animals, mean +EPs (mV +/- S.E.M.) for turns 1-4 in albinos were: 72.5 (2.5), 68.7 (2.3), 59.2 (2.7), 68.1 (3.3); pigmented values were: 72.9 (2.9), 66.9 (2.6), 53.8 (3.0), 57.0 (2.7). One-way ANOVAs did not show a significant difference in albino +EPs between any of the cochlear turns, but did indicate a highly significant difference between turns in the pigmented inner ears (P < 0.000004). Post hoc comparisons demonstrated +EPs in turns 3 and 4 were smaller than in turn 1. Since turn 3 was recorded last in these experiments, and was reduced in value relative to turn 4 in both groups, it is likely that cochlear deterioration contributed to this result more than any other factor. These results, combined with previous anatomical data, indicate that a diminution of melanocyte cell volume in the albino SV is accompanied by an increase in marginal cell volume density and larger +EPs in the higher cochlear turns, at least at resting levels. PMID- 8458748 TI - Regional differences in lectin binding patterns of vestibular hair cells. AB - Surface glycoconjugates of hair cells and supporting cells in the vestibular endorgans of the bullfrog were identified using biotinylated lectins with different carbohydrate specificities. Lectin binding in hair cells was consistent with the presence of glucose and mannose (CON A), galactose (RCA-I), N acetylglucosamine (WGA), N-acetylgalactosamine (VVA), but not fucose (UEA-I) residues. Hair cells in the bullfrog sacculus, unlike those in the utriculus and semicircular canals, did not strain for N-acetylglucosamine (WGA) or N acetylgalactosamine (VVA). By contrast, WGA and, to a lesser extent, VVA, differentially stained utricular and semicircular canal hair cells, labeling hair cells located in peripheral, but not central, regions. In mammals, WGA uniformly labeled Type I hair cells while labeling, as in the bullfrog, Type II hair cells only in peripheral regions. These regional variations were retained after enzymatic digestion. We conclude that vestibular hair cells differ in their surface glycoconjugates and that differences in lectin binding patterns can be used to identify hair cell types and to infer the epithelial origin of isolated vestibular hair cells. PMID- 8458749 TI - Hair cell regeneration in the bullfrog vestibular otolith organs following aminoglycoside toxicity. AB - Adult bullfrog were given single intraotic injections of the aminoglycoside antibiotic gentamicin sulfate and sacrificed at postinjection times ranging from 0.5 to 9 days. The saccular and utricular maculae of normal and injected animals were examined in wholemount and cross-section. Intraotic 200 microM gentamicin concentrations resulted in the uniform destruction of the hair bundles and, at later times, the cell bodies of saccular hair cells. In the utriculus, striolar hair cells were selectively damaged while extrastriolar hair cells were relatively unaffected. Regenerating hair cells, identified in sectioned material by their small cell bodies and short, well-formed hair bundles, were seen in the saccular and utricular maculae as early as 24-48 h postinjection. Immature versions of mature hair cell types in both otolith organs were recognized by the presence or absence of a bulbed kinocilia and the relative lengths of their kinocilia and longest stereocilia. Utricular hair cell types with kinocilia longer than their longest stereocilia were observed at earlier than hair cell types with shorter kinocilia. In the sacculus, the hair bundles of gentamicin treated animals, even at 9 days postinjection, were significantly smaller than those of normal animals. The hair bundles of utricular hair cells, on the other hand, reached full maturity within the same time period. PMID- 8458750 TI - Differential effects of age on click-rate and amplitude modulation-frequency coding in primary auditory cortex of the cat. AB - Recordings were made from 185 neurons in the primary auditory cortex of cats in the age range of 15 to 297 days. A comparison was made between the tuning for click repetition-rate and for amplitude modulation-frequency of a noise burst on the basis of temporal Modulation Transfer Functions (tMTF). 90 of the 185 units had a clear band-pass type tMTF for both repetition rate and modulation frequency, there was, however, no correlation between the respective Best Modulation Frequencies (BMF). Amplitude modulated noise (AMnoise) was the more effective stimulus in young kittens while click-train stimulation was more effective in adult cats. For all neurons with significant synchronization, BMFs for both click-train and AMnoise increased with age from about 4 Hz in kittens younger than 30 days to about 10 Hz in adult cats. In the approximately 50% of the neurons that were tuned both to click rate and modulation frequency, however, the BMF to AMnoise was consistently and significantly higher than that for clicks. In this group the mean BMF for kittens younger than 30 days were 7.94 Hz for AMnoise and 3.29 Hz for clicks and in the adults 10.91 Hz for AMnoise and 7.71 Hz for clicks. PMID- 8458751 TI - Contralateral auditory stimulation alters acoustic distortion products in humans. AB - It is now generally accepted that otoacoustic emissions (OAE) represent the only objective and non-intrusive means of functional exploration of the active micromechanical characteristics of the outer hair cells of the organ of Corti. Previous studies showed a decrease of the transiently evoked otoacoustic emissions and spontaneous otoacoustic emissions in humans, during acoustic stimulation of the contralateral ear, and attributed this effect to the medial efferent system. Such an effect has been shown on acoustic distortion product otoacoustic distortion emissions (DPOAE) in guinea pigs, but has not been investigated for DPOAEs recorded in humans, although DPOAEs represent the easiest means of exploring active micromechanical cochlear properties both in humans and in laboratory animals. The present study sought to investigate the existence and characteristics of a contralateral auditory stimulation effect on DPOAEs recorded in humans. This study shows that contralateral broad-band noise (BBN) has a suppressive effect on DPOAEs recorded from 0.5 kHz to 5 kHz. This effect is not due to air conduction, as no change in the noise floor occurred under increasing contralateral stimulation, and as no reduction in DPOAE amplitude was obtained in subjects whose contralateral ear was sealed with a plastic ear plug. Moreover, cross-over attenuation by bone transmission has been ruled out, as no change in DPOAE amplitude was recorded in the healthy ear of total unilaterally deaf patients during acoustic stimulation of the deaf ear. The effect seen was not entirely due to the acoustic reflex, as it was found and could indeed be even greater in subjects with no acoustic reflex. Results presented here show that the contralateral BBN effect is greater at low levels of ipsilateral stimulation, which leads us to discuss the involvement of both passive and active mechanisms in DPOAE generation at high stimulation levels. The contralateral BBN effect seems to be greater in mid frequency cochlear regions. There is strong evidence that the medial efferent system is involved and that afferent and efferent inputs are, at least partly, integrated at a brainstem level in order to ensure cochlear interaction. DPOAEs provide an interesting model for functional exploration of the efferent system, since they seem to be the only type of otoacoustic emission that can be recorded in both humans and in the majority of animals, and since results are obtained in the same way from both animals and humans, which allows experimental animal models very close to the human model. PMID- 8458752 TI - Cellular localisation of taurine in the organ of Corti. AB - The cellular localisation of taurine in the organ of Corti has been established using a monoclonal antibody and confocal fluorescence microscopy. The bulk of the taurine was found in the outer hair cells with very little present in the inner hair cells and supporting structures. The outer hair cells which probably function as an amplification/attenuation gain system, control inner hair cell output to the brain. Taurine is tentatively postulated as being related to calcium fluxes involved in outer hair cell response to sound or olivocochlear bundle stimulation. Other possibilities are also discussed. PMID- 8458753 TI - Interrelations between transiently evoked otoacoustic emissions, spontaneous otoacoustic emissions and acoustic distortion products in normally hearing subjects. AB - Active cochlear mechanisms and especially outer hair cells seem to be involved in oto-acoustic emissions (OAEs) genesis. This study sought to investigate basic characteristics of spontaneous otoacoustic emissions (SOAEs), click-evoked otoacoustic emissions (TOAEs) and interrelations between SOAEs, TOAEs and 2f1-f2 and 2f2-f1 distortion product OAEs (DPOAEs) in 135 normally hearing subjects. A gender effect was shown on TOAEs and DPOAEs amplitude, and is attributed to the higher incidence of SOAEs in women (58%) than in men (22%). Moreover, SOAEs presence seems to mask the age effect found, especially at high frequency components, on TOAEs amplitude. A general influence of SOAEs on TOAEs and DPOAEs is shown, especially at frequencies ranging from 1 kHz to 3 kHz, collecting more than 66% of the SOAEs peaks recorded. Lastly, correlations between TOAEs frequency band amplitude and 2f1-f2 DPOAEs amplitude, shows frequency specificity, at least at low frequencies (i.e., from 0.5 to 2 kHz) in agreement with previous works suggesting that the 2f1-f2 DPOAEs generation site is at the geometric mean of the primaries. The same correlations calculated with 2f2-f1 DPOAEs amplitude show frequency specificity at low frequencies i.e., at 800 Hz and 1600 Hz. 2f2-f1 DPOAEs in humans are shown to be generated near the 2f2-f1 frequency region on the cochlear partition. PMID- 8458754 TI - Protection from noise induced hearing loss: is prolonged 'conditioning' necessary? AB - The effect of prior 'conditioning' noise exposures on the protection from subsequent higher level exposures was studied using four groups of chinchillas. The three experimental groups were 'conditioned' using a 0.5 kHz octave band noise at 95 dB SPL for 6 h a day. The first group was exposed to the noise once and allowed to recover for nine days prior to the second exposure. The second and third groups were exposed for ten and twenty days respectively. The first group showed only small reductions in threshold shift (TS) following the second exposure. The other two groups showed significant reductions in TS with repeated exposures. Following the last 'conditioning' exposure, all three experimental groups were allowed to recover for five days before exposing them to the same noise at 106 dB SPL for 48 h. Threshold shifts recorded following the 106 dB exposure were compared against those recorded in a control group exposed only to the higher level. Each of the three experimental groups developed significantly less permanent threshold shifts than the control group. However, there were no significant differences among the three experimental groups and the differences in hair cell losses were insignificant. PMID- 8458755 TI - Development of GAD-immunoreactivity in the dorsal cochlear nucleus of the hamster and cat: light and electron microscopic observations. AB - Physiologic and pharmacologic evidence suggests that inhibitory influences are active in the mammalian dorsal cochlear nucleus (DCN) by the onset of hearing, while anatomical evidence suggests that inhibitory synapses are not present until days or weeks later. One inhibitory neurotransmitter in the DCN is gamma aminobutyric acid (GABA) and its presence can be indexed by immunohistochemical localization of its synthetic enzyme glutamic acid decarboxylase (GAD). The present study investigated the ingrowth and synapse formation of GAD immunoreactive inputs in the DCN of cat and hamster. GAD-immunoreactive puncta are present in the DCN of the cat at birth and of the hamster on postnatal day (PND) 3. Thus, the present data correlate well with the physiologic and pharmacologic evidence. In both species the first labelled puncta are near the dorsal acoustic stria and may originate from efferent axons in the stria. Several days later a band of labelled puncta is found in the fusiform cell layer. This location is equivalent to the termination zone of cartwheel cells, GAD immunoreactive interneurons in the DCN. Based on this spatiotemporal sequence in the appearance of GAD-immunoreactive puncta, we suggest that sources of GABA extrinsic to the DCN mature first, followed by intrinsic sources. PMID- 8458756 TI - Optimal modulation frequency for amplitude-modulation following response in young children during sleep. AB - In young children, there appears to be no advantage to recording steady-state response (SSR) at a stimulus rate of 40 Hz. To determine the optimal modulation frequency in auditory SSR evoked by sinusoidally amplitude-modulated (SAM) tones (amplitude-modulation following response: AMFR) in children during sleep and compare response patterns of AMFR at different modulation frequencies while awake with those during sleep, AMFR was examined in 10 adults with normal hearing while awake and during sleep and in 10 young children with normal hearing during sleep. The stimulus was a 1000 Hz, 50 dBnHL SAM tone with a modulation depth of 95%. Modulation frequency was varied from 20 to 200 Hz in 20 Hz steps. Response was determined by phase spectral analysis and the S/N ratio calculated by spectral amplitude at the modulation frequency and noise level around the modulation frequency using fast Fourier transform. Although AMFR was clearly evoked only by a modulation frequency of 40 Hz in adults while awake, AMFRs at modulation frequencies of 80 and 100 Hz were detected during sleep, in addition to 40 Hz AMFR. In children, 40 Hz AMFR was difficult to detect, but response could be clearly detected at higher modulation rates, especially at modulation frequencies of 80 and 100 Hz, compared with response in adults during sleep. Modulation frequencies from 80 to 100 Hz would thus appear optimal for detecting AMFR during sleep in children. PMID- 8458757 TI - Fodrin is a constituent of the cortical lattice in outer hair cells of the guinea pig cochlea: immunocytochemical evidence. AB - Localization of fodrin, a membrane skeletal protein, in the outer hair cell of the guinea pig cochlea was examined by immunocytochemical techniques. By immunofluorescence microscopy, fodrin was observed in the cuticular plate, in the infracuticular network and along the lateral wall. By immunoelectron microscopy of ultrathin cryosections, labeling for fodrin along the lateral wall was localized between the cell membrane and the outermost layer of the subsurface cisternae. Furthermore, pre-embedding immunoelectron microscopy of permeabilized specimens showed that most immunogolds for fodrin were on the thin cross-linking component of the cortical lattice. The results indicate that fodrin is a constituent of the cortical lattice which is thought to play an important role in outer hair cell motility. PMID- 8458758 TI - Does type I afferent neuron dysfunction reveal itself through lack of efferent suppression? AB - We present here two patients and three control subjects to demonstrate the clinical utility of studying evoked otoacoustic emissions and their contralateral suppression, as an aid to the delineation of afferent neuron dysfunction and possible lack of efferent suppression. The key patients here who fail to show contralateral suppression of their very robust otoacoustic emissions, concomitantly show paradoxically absent auditory brainstem responses (ABRs) and absence of middle ear muscle reflexes despite normal audiograms in the 2 kHz region and normal tympanograms. One of these patients has nearly normal pure tone sensitivity up to 3 kHz. The other has normal sensitivity in the 2 kHz region, but poor sensitivity on either side of that frequency. In addition, the two patients of interest show absent masking level differences and inordinately poor speech discrimination. Three 'foils' are presented: one patient with poor hearing on either side of 2 kHz, one with Bell's Palsy, and the third with bilateral temporal lobe disease. These patients show respectively that (1) isolated normal hearing at 2 kHz, (2) absence of middle ear muscle reflexes and (3) conscious cortical awareness of sound do not contribute directly to this intriguing clinical state. We propose that these patients with absent ABRs suffer from an auditory nervous system dysfunction which disrupts access to the efferent system. This condition also disables whatever systems contribute to the neural synchrony inherent in recording compound far-field action potentials such as the ABR. There are a number of hypotheses to be considered here. One suggests that the key patients are deficient in synchronous activation of Type I afferent fibers to the degree that they cannot activate efferent feedback, or they may be able to use only so-called Type II afferent neurons to support their normal zones of pure tone sensitivity. A less likely consideration focuses on the notion that discharge of primary neurons might be in some way synchronized by an efferent system which in these patients is the primary source of deficit. PMID- 8458759 TI - DiI reveals a prenatal arrival of efferents at the differentiating otocyst of mice. AB - We have reinvestigated the time of arrival of efferent fibers at the developing otocyst of mice employing diffusion of the lipophilic dye DiI in fixed tissue. In contrast to almost all previous reports, our data indicate a prenatal arrival of efferent fibers. A few efferent fibers were found to enter the eighth nerve root at embryonic day (ED) 10 1/2. Retrogradely labelled efferent cell bodies were at this stage coextensive with those of the facial motor nucleus, but started to segregate by ED 12. In contrast to retrogradely labelled facial motor neurons, labelled efferent neurons were bilaterally distributed in the hindbrain with a few projecting to both otocysts as early as ED 12. Anterograde labelling from the brain showed efferent fibers in the vestibular ganglion by ED 11. Invasion of the future vestibular sensory epithelia started by ED 12. Growth cones of efferent fibers had also reached the future cochlear sensory epithelium but invasion was only achieved by a few filopodia at this stage. The early arrival of efferents at the future sensory epithelia demonstrated here may allow an as yet unexplored interaction of efferent fibers with the proliferating and/or differentiating hair cells. PMID- 8458760 TI - Pure-tone masking profiles for human auditory brainstem and middle latency responses. AB - Several studies have compared the frequency selectivity of waves I and V of the auditory brainstem response (ABR) in humans, however little is known about the frequency selectivity of the middle latency response (MLR). Simultaneous recordings of ABRs and MLRs to 60 dB peSPL 2000-Hz probe tones were obtained in the presence of 0.5, 1.0, 1.41, 2.0, 2.83 and 4.0 kHz maskers presented at 40, 60, and 80 dB SPL. ABR/MLR iso-intensity masking profiles showing the percentage of the unmasked amplitudes as a function of frequency were constructed for ABR peak V-Vn and MLR peaks Na-Pa and Nb-Pb at each masker intensity. No significant differences were found between the frequency selectivity of the ABR and MLR, and the effects of masking on the amplitudes of these responses were similar. These results are consistent with the suggestion that frequency tuning is similar up to the level of the primary auditory cortex. PMID- 8458761 TI - A model of stereociliary tip-link stretches. AB - A model of the tip-link stretches produced by angular deflections of the stereocilia of vertebrate acoustico-lateralis hair cells is presented. It is shown that tip-link stretch in the model is proportional to the angle of stereociliary deflection. By contrast, the stretch of a horizontal (e.g., row-to row) link is proportional to the square of the angle of stereociliary deflection. Possible roles of these stretches in sensory transduction are discussed. PMID- 8458762 TI - Effect of lymph composition on an in vitro preparation of the alligator lizard cochlea. AB - The effects of different artificial lymphs on the cochlear duct of the alligator lizard were studied in an in vitro preparation. The duct was dissected and cemented to the glass floor of a chamber that had been filled with an artificial lymph. The vestibular membrane was removed and latex beads (1-5 microns in diameter) were allowed to settle on the endolymphatic surface of the duct. During perfusion with an artificial lymph solution, the positions of beads were measured and video images of the duct were obtained. Artificial lymphs were isosmotic and included artificial endolymph (AE), artificial perilymph (AP), Leibovitz's L-15 culture medium, an AE solution whose calcium concentration was the same as that of AP, and AE and AP solutions in which gluconate was substituted for chloride ions. Results obtained in AE were consistently different from those in other lymphs. The displacements of beads, the projected area of the papilla, the occurrence of blebs, and direct observation of cells in the duct all indicated that the tissue swelled in AE (with or without 2 mmol/l Ca) but showed no consistent shrinking or swelling in any of the other artificial lymphs. Thus for the solutions we used, the presence of both potassium and chloride was required to elicit the swelling response to isosmotic artificial lymphs. There were some regional differences in the swelling response: the swelling of the endolymphatic surface of the tissue in a direction orthogonal to the basilar membrane surface was smaller on the free-standing region of the basilar papilla than either on the tectorial membrane or on the hyaline epithelial cells. The preparation was osmotically stable in AP and in both AE and AP solutions in which gluconate was substituted for chloride ions. After exposure to these solutions for as much as 300 min, the preparation showed no gross signs of deterioration visible with the light microscope, and continued to exhibit a highly specific osmotic response to the composition of the bathing medium. PMID- 8458763 TI - Mean circulatory filling pressure: its meaning and measurement. AB - The volume-pressure relationship of the vasculature of the body as a whole, its vascular capacitance, requires a measurement of the mean circulatory filling pressure (Pmcf). A change in vascular capacitance induced by reflexes, hormones, or drugs has physiological consequences similar to a rapid change in blood volume and thus strongly influences cardiac output. The Pmcf is defined as the mean vascular pressure that exists after a stop in cardiac output and redistribution of blood, so that all pressures are the same throughout the system. The Pmcf is thus related to the fullness of the circulatory system. A change in Pmcf provides a uniquely useful index of a change in overall venous smooth muscle tone if the blood volume is not concomitantly changed. The Pmcf also provides an estimate of the distending pressure in the small veins and venules, which contain most of the blood in the body and comprise most of the vascular compliance. Thus the Pmcf, which is normally independent of the magnitude of the cardiac output, provides an estimate of the upstream pressure that determines the rate of flow returning to the heart. PMID- 8458764 TI - Acute hemorrhage in dogs: construction and validation of models to quantify blood loss. AB - We examined the ability of commonly used clinical parameters to quantify acute hemorrhage in dogs. Eight animals were bled 40 ml/kg body wt over 100 min. Ten hemodynamic and 20 blood laboratory parameters were obtained every 10 min to construct, with use of linear regression analysis, models that quantify blood loss. During model construction, the best indicator of quantity of hemorrhage was arterial base deficit [ABD; coefficient of variation (CV) 35%]. This model was more accurate (P < 0.05) than 27 others (CV range 43 to 63%) and similar to systolic (CV 40%) and mean (CV 40%) arterial pressures. In validation studies in 10 additional animals, our best models based on ABD and systolic and mean arterial pressures each unexpectedly showed a significant (P < 0.05) decrease in accuracy (CV 86, 57, and 60%, respectively) attributable to large baseline (before hemorrhage) variability among animals. To eliminate this variability, models based on changes from baseline measurements were investigated. The best predictor of change in blood volume was change in ABD (CV 27%). This model was significantly (P < 0.05) more accurate than any of 27 others (CV range 36 to 65%) and similar to change in venous base deficit and venous pH (each CV 31%). When validated, acid-base models such as ABD, venous pH, and arterial bicarbonate were the best predictors of volume change (CV range 28 to 40%). With the use of multivariate analysis, pairwise combinations of single parameter models (n = 465) improved prediction errors only minimally. In summary, most commonly used hemodynamic and blood indexes could not be validated as accurate measurements in quantifying hemorrhage. In contrast, changes in acid-base parameters were validated as moderately accurate predictors of blood volume changes and therefore may have utility in the assessment of patients with ongoing hemorrhage. PMID- 8458765 TI - Muscle damage is not a function of muscle force but active muscle strain. AB - Contractile properties of rabbit tibialis anterior muscles were measured after eccentric contraction to investigate the mechanism of muscle injury. In the first experiment, two groups of muscles were strained 25% of the muscle fiber length at identical rates. However, because the timing of the imposed length change relative to muscle activation was different, the groups experienced dramatically different muscle forces. Because muscle maximum tetanic tension and other contractile parameters measured after 30 min of cyclic activity with either strain timing pattern were identical (P > 0.4), we concluded that muscle damage was equivalent despite very different imposed forces. This result was supported by a second experiment in which the same protocol was performed at one-half the strain (12.5% muscle fiber length). Again, there was no difference in maximum tetanic tension after cyclic 12.5% strain with either strain timing. Data from both experiments were analyzed by two-way analysis of variance, which revealed a highly significant effect of strain magnitude (P < 0.001) but no significant effect of stretch timing (P > 0.7). We interpret these data to signify that it is not high force per se that causes muscle damage after eccentric contraction but the magnitude of the active strain (i.e., strain during active lengthening). This conclusion was supported by morphometric analysis showing equivalent area fractions of damaged muscle fibers that were observed throughout the muscle cross section. The active strain hypothesis is described in terms of the interaction between the myofibrillar cytoskeleton, the sarcomere, and the sarcolemma. PMID- 8458766 TI - Absence of a growth hormone effect on rat soleus atrophy during a 4-day spaceflight. AB - The objectives of the present study were to determine the size and enzyme properties of soleus fibers of rats subjected to a 4-day spaceflight (National Aeronautics and Space Administration, STS-41) and the effects of exogenous growth hormone (GH) on the atrophic response of the muscle. Four groups of rats were studied: 1) control (Con), 2) Con plus GH treated (Con + GH), 3) flight (Fl), and 4) F1 plus GH treated (Fl + GH). Cross-sectional area and the activities of succinate dehydrogenase and myofibrillar adenosinetriphosphatase (ATPase) were determined in fibers identified in frozen serial cross sections. Fibers were categorized immunohistochemically as slow, fast, or slow-fast on the basis of their reaction with slow and fast myosin heavy-chain (MHC) monoclonal antibodies. Fibers also were categorized as light or dark on the basis of their staining for ATPase at pH 8.6. After the 4-day flight, mean body weight was significantly decreased compared with control. The absolute and relative (muscle wt/body wt) soleus weights were significantly smaller in the Fl and Fl + GH rats compared with their respective ground-based controls. In both flight groups, the cross sectional area of the light ATPase fibers was significantly smaller (approximately 30%) than control. Three of 11 flight rats had a higher proportion of fibers expressing both slow and fast MHCs than expected on the basis of the fiber type distribution in the 11 control rats. Mean fiber succinate dehydrogenase and ATPase activities were similar among the four groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458767 TI - Mapping of electrical muscle stimulation using MRI. AB - The purpose of this study was to map the pattern of muscle contractile activity elicited by electromyostimulation (EMS). A secondary interest was to determine whether EMS evoked a different pattern of contractile activity than voluntary (VOL) efforts. These objectives were addressed by examining the pattern and extent of contrast shift in magnetic resonance (MR) images after isometric actions of the left m. quadriceps of seven subjects had been elicited by EMS (1-s train of 500-microseconds sine wave pulses at 50 Hz) or by VOL means. For both conditions, five sets of 10 muscle actions were executed at each of the three force levels equal to 25, 50, and 75% of maximal VOL isometric torque. There were 1-s, 1.5-min, and 30-min rests between muscle actions, sets, and torque levels, respectively. Transaxial proton MR images (TR/TE = 2,000/30, 60) of m. quadriceps femoris were obtained with a 1.5-T imager at rest and after completion of the five sets of isometric actions at each force level. MR image contrast shift, as indicated by T2 values > 1 SD above the mean resting muscle T2, was calculated per pixel. Torque declined approximately 18% (P < 0.05) during each EMS set independent of the preset relative force level but recovered between sets. EMS increased T2 values above rest (29 +/- 0.2 to 36 +/- 0.5, P < 0.05) in regions of muscle dispersed throughout a given cross section. The pattern of muscle stimulation, as reflected by increased T2 values, varied markedly among subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458769 TI - Centrally administered ouabain aggravates central sleep apneas. AB - The presence of endogenous digitalis-like factors in the central nervous system suggests their functional significance in the central nervous system. Three-day infusions of three-stepped doses of the digitalis agent ouabain (1-100 ng.kg body wt-1.h-1) into the lateral cerebral ventricle of freely moving rats caused a dose dependent increase in the number of central-apneic episodes during rapid-eye movement sleep without affecting the time spent in rapid-eye-movement sleep or basic respiratory rate. These results suggest that endogenous digitalis-like factors may be involved in the genesis of central sleep apneas. PMID- 8458768 TI - Airway-parenchymal interdependence and bronchial responsiveness in two highly inbred rat strains. AB - To investigate if airway-parenchymal interdependence may account for differing bronchial responsiveness between inbred rat strains, Fisher and Lewis 12-wk-old male rats were anesthetized, tracheostomized, and placed in a pressure plethysmograph. Functional residual capacity, total lung capacity [lung volume at transpulmonary pressure (PL) of 30 cmH2O], and specific compliance were determined and were found to be similar. Rats were paralyzed and mechanically ventilated. Concentration-response curves were constructed by calculating lung resistance (RL) and lung elastance (EL) after nebulization of saline and then doubling doses of methacholine (0.0625-512 mg/ml). In Fisher (n = 8) and Lewis (n = 7) rats RL and EL were again determined at a lung volume corresponding to 2 cmH2O PL above FRC. The doubling, maximal, and half-maximal effective concentrations were determined for RL and EL. The doubling of effective concentrations of RL and EL were significantly less for Fisher rats. Other groups of Fisher (n = 5) and Lewis (n = 5) rats were similarly exposed to three concentrations of methacholine (64, 128, and 256 mg/ml), and determinations of RL and EL were made at lung volume corresponding to PL of 0, 2, 4, and 8 cmH2O. In both groups, Lewis rats exhibited a significant effect of volume on maximal RL and EL, whereas Fisher rats did not. The absence of volume effect on bronchoconstriction in the hyperresponsive Fisher strain is consistent with the hypothesis that altered airway-parenchymal interdependence contributes to bronchial hyperresponsiveness. PMID- 8458770 TI - NG-monomethyl-L-arginine paradoxically relaxes preconstricted canine intrapulmonary arteries. AB - We studied the effects of NG-monomethyl-L-arginine (LMMA), a nitric oxide (NO) synthesis inhibitor, in canine intrapulmonary arteries constricted with phenylephrine. Isolated vessels were suspended in organ chambers containing modified Krebs solution, and isometric tensions were recorded. In contrast to the expected constriction predicted from other studies, LMMA instead caused dose dependent vasorelaxation in phenylephrine-constricted canine pulmonary arteries. LMMA (1 and 10 microM) reduced the phenylephrine contraction by 5 and 23%, respectively. Similar dose-dependent relaxations were observed with NG-monomethyl D-arginine (DMMA) but not with L-arginine (L-Arg), N epsilon-methyl-L-lysine, and another NO synthesis inhibitor, N omega-nitro-L-arginine (LNA), suggesting that a methyl group positioned at the guanidino-nitrogen is important in these responses. Vasorelaxation induced by LMMA and DMMA was not affected by pretreatment with the NO precursor L-Arg; however, responses were abolished by dissimilar cyclooxygenase inhibitors indomethacin (10 microM) and meclofenamate (2 microM). Pretreatment of vessels with LNA (100 microM) augmented LMMA-induced relaxations but attenuated DMMA-induced responses. LMMA- and DMMA-induced vasorelaxations were also observed in endothelium-rubbed vessels; DMMA-induced vasorelaxations were similar in vessels with and without endothelium, whereas LMMA-induced relaxations were increased in endothelium-rubbed vessels. These data suggest that LMMA and DMMA induced vasorelaxation by causing synthesis of dilator prostaglandins, which was independent of the presence of endothelial cells and the L-Arg-NO pathway. In addition, both endothelium removal and LNA pretreatment augmented LMMA-induced but not DMMA-induced relaxations, suggesting that inhibition of NO synthesis by LMMA opposes its cyclooxygenase-dependent vasorelaxant effects. PMID- 8458771 TI - Vascular conductance and aerobic power in sedentary and active subjects and heart failure patients. AB - The relationship between peak aerobic power and a strain-gauge determination of local skeletal muscle vascular conductance 10-13 s after calf exercise to fatigue was examined in 21 middle-aged adults (age 38.1 +/- 2.5 yr): seven physically active men (A), seven sedentary men (S), and six men and one woman with compensated idiopathic heart failure (HF). The three subgroups were chosen as differing widely in peak O2 intake [48.2 +/- 1.2, 32.9 +/- 1.6, and 16.1 +/- 1.3 (SE) ml.kg-1 x min-1, respectively]. Calf vascular conductance showed a gradation with aerobic power: 64.8 +/- 3.8, 40.7 +/- 4.3, and 30.7 +/- 6.1 (SE) ml/min local flow per 10 liters of tissue per unit of blood pressure. There was a strong positive correlation between O2 intake and vascular conductance for the overall group (VO2 = 0.614 G + 3.5; r = 0.75, P < 0.001) and for the 14 normal subjects (VO2 = 0.377 G + 20.6; r = 0.74, P < 0.002). The mean conductance was smaller in HF (P < 0.001), with no significant slope in relation to O2 intake. There was no relationship between the resting cardiac ejection fraction [74.4 +/- 4.1% (SE) for A, 74.3 +/- 4.2% for S, and 25.8 +/- 5.2% for HF] and either peak aerobic power or calf vascular conductance. We conclude that peak aerobic power is strongly associated with local vascular conductance during peripherally limited exercise involving the calf muscles of one leg and that vascular conductance is particularly low in subjects with compensated idiopathic heart failure. PMID- 8458772 TI - Central and spinal effects of sodium cyanide on respiratory activity. AB - The pharmacological actions of cyanide on respiratory activity have been known for some time and are attributed mainly to effects on peripheral chemoreceptors. In the studies reported here, we have examined the acute central effects of cyanide when applied topically to the ventral surface of the medulla (VMS) and when administered into the spinal intrathecal space at the C5-T3 level on activities of the phrenic nerve, diaphragm, parasternal intercostal, triangularis sterni, and transversus abdominis muscles. Topical application of 10-100 micrograms (10 microliters of 1-10 mg/ml) cyanide to the intermediate area of the VMS decreased respiratory activity by > 50%, and expiratory muscles were more sensitive to inhibition than inspiratory muscles. The onset of depression of phrenic nerve or respiratory muscle activity occurred within 20 s of administration, and the effects reversed after washout. In contrast, intrathecal administration of cyanide in doses of 10-100 micrograms (100 microliters of 0.1-1 mg/ml) increased electrical activity of the respiratory muscles. Diaphragm activity changed from 17 +/- 2 to 42 +/- 8 (SE) units (P < 0.01), parasternal intercostal activity increased from 18 +/- 3 to 46 +/- 9 units (P < 0.01), and expiratory activity of the chest wall and abdominal muscles increased from 9 +/- 2 to 39 +/- 10 units (P < 0.05). Both topical application on the VMS and intrathecal administration of cyanide caused an increase in arterial blood pressure and a slight insignificant acceleration of heart rate. These data suggest that cyanide acting on the VMS causes respiratory depression and enhancement of sympathetic outflow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458773 TI - Microvascular damage in the cortex of cat brain from middle cerebral artery occlusion and reperfusion. AB - Oxygen-dependent quenching of phosphorescence provides an extraordinarily powerful method for examining the effects of ischemia/hypoxia on the cortex of the brain. Video camera technology has permitted imaging, through a window in the skull, of the phosphorescence of an oxygen probe, Pd meso-tetra-(4-carboxyphenyl) porphine, bound to albumin in the blood of anesthetized animals. Images of the phosphorescence taken at different times after the flash of excitation light were used to generate high-resolution two-dimensional maps of the oxygen pressure. These maps show that cortical oxygenation is spatially heterogeneous and that there is dynamic time-dependent modulation of regional oxygen pressures. When the middle cerebral artery was occluded, the region for which it supplied blood became hypoxic, the severity of the hypoxia varying among animals. Release after 60 min of occlusion resulted in a rapid rise of the oxygen pressure to above normal levels followed by onset of a delayed period of hypoxia. This period is characterized by generally low tissue oxygen pressures with local regions of more severe hypoxia. The delayed period of hypoxia appears to result from damage to the microvasculature, and this microvascular damage is proposed to be an important determinant of the extent of irreversible brain damage. PMID- 8458774 TI - Effects of naloxone on the sensation of dyspnea during acute respiratory stress in normal adults. AB - To clarify whether endogenous opioids modulate the dyspnea intensity and, if so, by what mechanism they act on it, we examined 12 healthy male volunteers aged 19 27 yr for ventilatory and peak mouth pressure (Pm) responses to hypoxic progressive hypercapnia with inspiratory flow-resistive loading after the intravenous infusion of 3 mg of naloxone or saline. The intensity of dyspnea was simultaneously assessed by visual analogue scaling every 15 s. Naloxone administration increased both ventilatory and Pm responses to hypoxic progressive hypercapnia (P < 0.05 for both). The increase in dyspnea intensity for a given increase in end-tidal PCO2 was significantly greater after naloxone infusion than after saline (P < 0.05). However, there were no differences in the increase in dyspnea intensity for a given increase in minute ventilation or Pm. These results suggest that the endogenous opioid system suppresses the respiratory output under a strong, acute respiratory stress in normal adults and that this system may relieve the dyspnea sensation secondary to the suppression of the brain stem respiratory center without specific effects on the processing of respiratory sensations in the higher brain. PMID- 8458775 TI - Food restriction-induced transformations in cardiac functional and biochemical properties in rats. AB - The primary objective of this study was to ascertain if various degrees of marked chronic food restriction (FR) as well as the combination of FR and exercise training of moderate intensity induce changes in the functional properties of the heart that are consistent with previously reported findings indicative of downregulation of high-adenosinetriphosphatase V1 isomyosin expression. Adult female rodents were randomly assigned to one of four experimental groups: 1) free eating, 2) 50% food restricted, 3) 75% food restricted, or 4) 50% food restricted plus treadmill trained. Results show that FR induced significant depression in the functional properties (heart rate, left ventricular pressure, rate of pressure development, and double product) of the heart in all FR groups and that this depression in functional capacity corresponded to the degree of FR. These functional changes were accompanied by significant downregulation of the alpha- and upregulation of the beta-myosin heavy chain gene expressions, as studied at both the mRNA and protein levels. The exercise training induced further alterations in cardiac function; however, these alterations occurred independently of any shifts in isomyosin composition. These results suggest that although severe FR is a potent stimulus to transform both the biochemical and functional properties of the rodent heart, the underlying mechanism(s) concerning these adaptations remains unresolved. PMID- 8458776 TI - Peripheral pulmonary vascular resistance. AB - The pressure-flow relationship has been studied in a peripheral portion of the lung vasculature in anesthetized dogs with use of a double-lumen catheter wedged in a distal pulmonary artery. One lumen was used to infuse mixed venous blood in the wedged area and the other to measure the corresponding perfusion pressure. Flow ranged from 0 to 9.2 ml/min, and the mean volume of the wedged area (n = 59) was 0.75 +/- 0.05 (SE) ml. In the areas where the distal pulmonary artery was in the same direction as the catheter ("coaxial"), the mean pressure-flow curve showed a negligible gamma-intercept and no significant difference between ascending and descending flow. The slope of the initial part of the ascending limb (peripheral pulmonary vascular resistance) varied from site to site and did not show a significant correlation with the overall pulmonary vascular resistance; it was inversely correlated with the volume of the wedged area (r = 0.35, P < 0.05) and directly, as expected, correlated with the y-intercept (r = 0.78, P < 0.001) and hysteresis (r = 0.48, P < 0.001). The results of two consecutive pressure-flow runs in the same site showed similar results, with no difference exceeding the error of measurement. In contrast, the slope increased by 71% during hypoxia (fraction of inspired O2 was 0.10, n = 5). This procedure seems suitable to determine the effects of physiological or pharmacological interventions on the pulmonary vessels, without interference of the systemic circulation. PMID- 8458777 TI - Influence of respiration on heart rate and blood pressure fluctuations. AB - The dynamics of the respiratory and cardiovascular systems were studied by continuously slowing respiration from 0.46 to 0.05 Hz. The time-frequency distribution and global spectral analysis were used to assess the R-R interval (R R) and the systolic and diastolic blood pressure fluctuations in 16 healthy subjects. During rest, the nonrespiratory-to-respiratory frequency ratios were not affected by occasional slow breathing, whereas the low- (0.01-0.15 Hz) to high- (0.15-0.3 Hz) frequency indexes for blood pressure were increased (P < 0.05). The respiratory fluctuations in R-R and the systolic and diastolic pressures were paced over the 0.46- to 0.05-Hz range. As respiration slowed to 0.07-0.09 Hz, the frequency content of the respiration and cardiovascular variables increased sharply and nonlinearly to a maximum that exceeded values at higher frequencies (P < 0.001). The nonrespiratory frequency content remained stable in the 0.01- to 0.05-Hz range and did not significantly differ from that at rest. In contrast, the nonstable 0.05- to 0.1-Hz component was suppressed. A slow 0.012- to 0.017-Hz rhythm modulated respiration and hemodynamic fluctuations at both respiratory and nonrespiratory frequencies. The study indicated that respiration input should be considered in the interpretation of global spectra. Furthermore the time-frequency distributions demonstrated that a close nonlinear coupling exists between the respiratory and cardiovascular systems. PMID- 8458778 TI - Oxygen radicals in bronchoconstriction of guinea pigs elicited by isocapnic hyperpnea. AB - The role of oxygen radicals in isocapnic hyperpnea-induced bronchoconstriction (HIB) of guinea pigs was investigated using scavengers of the radicals. In series 1, 50 young guinea pigs were randomly divided into seven groups: control 1, control 2, chlorisondamine, tetrodotoxin (TTX), acute dimethylthiourea (DMTU), tachykinin depletion, and 5% CO2 in air. Animals of the control 2 group received vehicle (saline) infusion while those of the control 1 group did not. Chlorisondamine was used to block ganglionic transmission, TTX to interrupt nerve conduction, DMTU to scavenge hydroxyl radicals, and chronic capsaicin pretreatment to deplete tachykinins. The animals in the last group were ventilated with dry 5% CO2 in air during hyperpnea. In series 2, 13 additional animals were used to test the effects of intratracheal administration of superoxide dismutase and catalase (SOD + CAT) on HIB. Each animal was anesthetized with pentobarbital sodium, cannulated with a tracheal cannula and venous catheter, paralyzed with gallamine triethiodide, and mechanically ventilated. During the baseline period, each animal was ventilated normally with humidified air. Then it was hyperventilated 15 min with a dry gas mixture of 95% O2-5% CO2, except animals in the last group of series 1. Subsequently, all animals returned to normal ventilation with humidified air for 45 min (recovery period). The maximal expiratory flow and dynamic compliance were obtained periodically during the recovery period. The isocapnic hyperpnea using 95% O2-5% CO2, but not 5% CO2 in air, caused bronchoconstriction that was significantly blocked by acute DMTU, acute SOD + CAT, and tachykinin depletion. In an additional group of six animals, acute DMTU did not significantly alter acetylcholine-induced airway constriction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458779 TI - Effects of pH and SO2 on solubility coefficients of inert gases in human whole blood. AB - We systematically investigated the quantitative importance of pH and O2 saturation (SO2) of hemoglobin on the solubility coefficients (alpha) for six inert gases: sulfur hexafluoride, N2, ethane, cyclopropane, halothane, and diethyl ether. Measurements of alpha were made at 37 degrees C with SO2 of 0-1.0 and pH of 7.2-7.7 by use of whole blood obtained from three healthy subjects. No significant dependence of alpha on pH was demonstrated for sulfur hexafluoride, N2, halothane, or diethyl ether, but an appreciable augmentation of alpha with increasing pH was found for ethane and cyclopropane. No alpha value obtained for oxygenated blood differed statistically from that for deoxygenated blood. In addition to the basic findings on the effects of pH on alpha values of ethane and cyclopropane with the multiple inert gas elimination technique (data obtained from 22 patients with either interstitial pneumonia or chronic obstructive pulmonary disease), we also found that dependence of alpha on blood pH exerted no significant influence on the recovery of ventilation-perfusion distribution in the lung. We concluded that: 1) pH plays an appreciable role in determining gas solubilities in blood, 2) SO2 is not a decisive factor for gas solubilities in blood, and 3) the influence of various pH values in pulmonary capillaries on inert gas exchange is negligible. PMID- 8458780 TI - Diaphragmatic activity induced by cortical stimulation: surface versus esophageal electrodes. AB - Evoked responses of the diaphragm can be induced by magnetic cortical stimulation and recorded by either surface or esophageal electrodes. The former recording system is tolerated better by the patient but has potential problems with the specificity of the diaphragmatic signal. This study compares the responses of the diaphragm to cortical stimulation that were recorded simultaneously with surface and esophageal electrodes on seven patients (61 +/- 4 yr) with chronic obstructive pulmonary diseases. Stimuli were delivered in three ventilatory conditions: at baseline, during deep breathing, and during voluntary panting. No differences were observed between results recorded by surface and esophageal electrodes [amplitude of the compound motor of the action potential (CMAP), 0.8 +/- 0.1 vs. 0.8 +/- 0.1 mV, NS; latency, 13.1 +/- 0.4 vs. 12.6 +/- 0.5 ms, NS]. In addition, significant correlations were found (CMAP, r = 0.77, P < 0.001; latency, r = 0.71, P = 0.002). The concordance analysis, however, indicated some dissimilarity between the recordings of the electrodes (CMAP, R1 = 0.31; latency, R1 = 0.26). These differences may be due to the area of the muscle mainly recorded by each electrode and/or to the additional activity from other muscles recorded by surface electrodes. On the other hand, the diaphragmatic responses observed in these patients with chronic obstructive pulmonary diseases were similar to those previously reported in healthy subjects. PMID- 8458781 TI - Toward a kinetic theory of connective tissue micromechanics. AB - The aim of this study is to develop unifying concepts at the microstructural level to account for macroscopic connective tissue dynamics. We establish the hypothesis that rate-dependent and rate-independent dissipative stresses arise in the interaction among fibers in the connective tissue matrix. A quantitative theoretical analysis is specified in terms of geometry and material properties of connective tissue fibers and surrounding constituents. The analysis leads to the notion of slip and diffusion boundary layers, which become unifying concepts in understanding mechanisms that underlie connective tissue elasticity and energy dissipation during various types of loading. The complex three-dimensional fiber network is simplified to the interaction of two ideally elastic fibers that dissipate energy on slipping interface surfaces. The effects of such interactions are assumed to be expressed in the aggregate matrix. Special solutions of the field equations are obtained analytically, whereas the general solution of the model field equations is obtained numerically. The solutions lead to predictions of tissue behavior that are qualitatively, if not quantitatively, consistent with reports of a variety of dynamic moduli, their dependencies on the rate and amplitude of load application, and some features associated with preconditioning. PMID- 8458782 TI - Developmental differences in vascular smooth muscle mechanics in pulmonary and systemic circulations. AB - To evaluate the maturational changes in vascular muscle mechanics we studied and compared the isotonic half-time relaxation (t1/2P,CE) and maximal load-bearing capacity normalized to stress of pulmonary and systemic arterial muscle from perinatal and adult sheep. For the pulmonary and systemic vessels t1/2P,CE was significantly shorter in adult than in perinatal sheep (P < 0.01). In newborns t1/2P,CE of the pulmonary vessels was 185 +/- 31 (SE) s, longer than that of the systemic vessels (64 +/- 10 s; P < 0.01). In adults t1/2P,CE of the pulmonary vessels (101 +/- 14 s) was longer than that of the systemic vessels (37 +/- 5 s; P < 0.01). Maximal load-bearing capacities normalized to stress of pulmonary vessels of fetal and newborn sheep were twofold greater than those of adult sheep and of the systemic vessels of newborns and adults (P < 0.01). In conclusion, significant maturational changes in the isotonic and isometric mechanical properties of vascular pulmonary and systemic smooth muscle were observed in sheep. PMID- 8458783 TI - Lung volume and effectiveness of inspiratory muscles. AB - We related inspiratory muscle activity to inspiratory pressure generation (Pmus) at different lung volumes in five seated normal subjects. Integrated electromyograms were recorded from diaphragmatic crura (Edi), parasternals (PS), and lateral external intercostals (EI). At 20% increments in the vital capacity (VC) subjects relaxed and then made graded and maximal inspiratory efforts against an occluded airway. At any given level of pressure generation, Edi, PS, and EI increased with increasing lung volume. The Pmus generated at total lung capacity as a fraction of that at a low lung volume (between residual volume and 40% VC) was 0.39 +/- 0.15 (SD) for the diaphragm, 0.20 +/- 0.06 for PS, and 0.22 +/- 0.04 for the lateral EI muscles. Our results indicate a lesser volume dependence of the Pmus-EMG relationship for the diaphragm than for PS and EI muscles. This difference in muscle effectiveness with lung volume may reflect differences in length-tension and/or geometric mechanical advantage between the rib cage muscles and the diaphragm. PMID- 8458784 TI - Regional diaphragmatic length and EMG activity during inspiratory pressure support and CPAP in awake sheep. AB - We examined diaphragmatic mechanics in awake sheep during quiet breathing (QB) and the randomized application of 5, 10, and 15 cmH2O continuous positive airway pressure (CPAP), inspiratory pressure support (IPS), and equal combinations of IPS and CPAP (IPS/CPAP). We measured esophageal, gastric, and transdiaphragmatic (Pdi) pressures and regional length, shortening, and electromyogram (EMG) activity of both costal and crural diaphragmatic segments. Segmental resting length normalized to QB decreased during 15 cmH2O CPAP (costal, 19.2 +/- 3.3%; crural, 7.5 +/- 2.1%; P < 0.05) and during 15/15 cmH2O IPS/CPAP (costal 25.3 +/- 4.8%, crural 9.9 +/- 2.6%; P < 0.05). Only during 15 cmH2O IPS did costal shortening fraction increase (67% QB; P < 0.05). Compared with QB, during 15 cmH2O CPAP, end-tidal CO2 increased 6 Torr, regional EMG activity increased threefold, and Pdi increased 58%. During 15 cmH2O IPS these values decreased 3 Torr, threefold, and 44% respectively, but during IPS/CPAP they remained unchanged. Expiratory gastric pressure (Exp-Pga) reached 4.3 +/- 0.4 cmH2O at 15 cmH2O CPAP, but during IPS/CPAP Exp-Pga was less (maximum of 1.7 +/- 0.4 cmH2O) than at comparable CPAP (P < 0.05), despite the shorter diaphragmatic length. We conclude that: 1) IPS alters the actions of the diaphragm during CPAP, 2) Exp-Pga is poorly coupled to diaphragmatic end-expiratory length, and 3) both IPS and the release of Exp-Pga assist active diaphragmatic shortening. PMID- 8458785 TI - Thyroarytenoid muscle activity in sleep apneas. AB - In normal subjects the thyroarytenoid muscle (TA), a vocal cord adductor, has phasic expiratory activity during wakefulness that disappears during non-rapid eye-movement (NREM) sleep. Fiber-optic studies have reported absent or irregular vocal cord movements during obstructive apneas and vocal cord adduction during central apneas. This study was designed to investigate TA activity during NREM sleep in 14 subjects with sleep apnea by means of intramuscular wire electrodes. During central apneas, which were recorded in three subjects, continuous TA activity was observed. During obstructive apneas, which were recorded in all subjects, two different patterns of TA activity were observed: 1) absence of any activity until arousal and 2) phasic activity throughout the apnea. The first pattern was detected in six subjects, whereas both patterns were observed in the remaining eight subjects. No correlation was found between obstructive apnea characteristics and presence or absence of TA activity. In all subjects TA underwent a marked activation during arousal. While nasal continuous positive airway pressure was applied during NREM sleep TA activity was always absent. The persistence of TA activity during central apneas suggests that they may represent an extreme prolongation of neural expiratory discharge. We speculate that a variable interaction of different stimuli acting during obstructive apnea may activate TA, which, in turn, may contribute to glottic narrowing. PMID- 8458786 TI - Reduction of oxylabile CO2 in human blood by lactate. AB - The influence of lactic acid, hydrochloric acid, and sodium lactate addition (10 mmol/l each) on oxylabile CO2 was investigated in blood of male subjects after equilibration at 37 degrees C with 3, 6, and 10% CO2 in N2 and O2, respectively. The total CO2, pH in whole blood and erythrocytes, oxygen saturation, hemoglobin concentration, and hematocrit value were measured. With these data we calculated bicarbonate and carbamate concentrations and the corresponding differences between oxygenated and deoxygenated blood. The amount of oxylabile bicarbonate was not systematically influenced by the various experimental conditions. The carbamate content, however, was larger in deoxygenated than in oxygenated blood (up to 0.08 mol/mol hemoglobin) only in the absence of lactate. In the presence of lactic acid as well as sodium lactate, the carbamate content in oxygenated blood was higher by 0.06-0.13 mol/mol hemoglobin than in deoxygenated blood. The lactate effect even increased after 2,3-diphosphoglycerate depletion. We suggest, therefore, a competition between CO2 and the lactate ion at the NH2-terminal valine of the beta-globin chain in deoxygenated hemoglobin. PMID- 8458787 TI - Influence of carbon dioxide kinetics on pulmonary carbon dioxide exchange. AB - In the absence of erythrocytes, carbonic anhydrase (CA) localized to the pulmonary capillary endothelium catalyzes the dehydration of bicarbonate to CO2. We studied the effects of lung CA and the reactions of CO2 on CO2 excretion in isolated lungs perfused with buffer. In indicator-dilution experiments, recoveries of dissolved CO2 and acetylene (C2H2) in the venous effluent were delayed significantly compared with a vascular indicator because the gases were distributed in both the vascular and alveolar volumes. In a second group of experiments, the kinetics of CO2 excretion were monitored with a plethysmographic method after injection of a bolus containing dissolved CO2 or bicarbonate. Exchange was compared with excretion of dissolved C2H2. The rate of excretion of dissolved CO2 and C2H2 was identical, indicating that CO2 is exchanged in the same manner as an inert gas. When bicarbonate was injected, CO2 excretion lagged behind C2H2 excretion by approximately 0.3 s. Inhibition of lung CA with acetazolamide reduced the quantity of CO2 exchanged to one-fourth of control and decreased the delay in exchange by one-half. PMID- 8458788 TI - Endurance training increases arterial wall thickness in rats. AB - We tested whether endurance training altered the morphology of systemic arteries. Female Sprague-Dawley rats (8 wk, 120 g) were either treadmill run for 16 wk (up to 3 h/day, 5-10% grade, 35 m/min) or used as caged controls (n = 7/group). At 24 h post-running bout, rats were anesthetized (ether) and decapitated. Soleus muscles were excised for determination of citrate synthase activity [control, 38.4 +/- 5.6 (SE); trained, 56.3 +/- 5.3 mumol.min-1 x g-1; P < 0.05]. The cervical stump was ligated, and the vascular system was perfused via the left ventricle at systemic pressure of 80 mmHg: first with papaverine (0.3 mM in phosphate-buffered saline, pH 7.4, 37 degrees C) to relax smooth muscle cells (SMC) and then with aldehyde fixative solution. The abdominal aorta and femoral, axillary, superior mesenteric, and coeliac arteries were excised, postfixed in OsO4, and embedded in Spurr resin. Vessel cross sections were stained for histological analysis using light microscopy and videomicroscopy. In trained rats, all vessels (except coeliac) had 12-18% greater (P < 0.05) medial wall thickness; total wall area was elevated (P < 0.05) in the femoral and axillary arteries and the abdominal aorta. Neither lumen diameter nor the number of SMC nuclei per vessel cross section was different between groups for any vessel. These findings indicate growth of the arterial media without an increase of SMC number in response to endurance training. This adaptation will decrease tangential wall stress of arteries at rest and during exercise. PMID- 8458789 TI - Skin vascular reactivity in healthy subjects: influence of hormonal status. AB - To investigate the influence of the hormonal status on skin vascular reactivity, 18 males, 18 women using oral contraceptives (oc), 17 premenopausal, and 18 postmenopausal women were studied. Finger skin temperature (FST, in degrees C) and laser Doppler flux (LDF, in perfusion units) were measured during heating (45 degrees C water bath) and cooling (15 degrees C) followed by a subsequent recovery period. Maximal heat-induced vasodilation was significantly higher in women using oc and in premenopausal women when compared with males. During cooling, FST and LDF were significantly higher in males compared with women using oc and premenopausal women, respectively. FST was also higher in postmenopausal women than in women using oc. During recovery, FST and LDF were significantly higher in males than in women using oc, and LDF was also higher in males than in premenopausal women. These findings are consistent with a less pronounced and less prolonged cold-induced vasoconstriction in males. Other hemodynamic (blood pressure or heart rate) or biological factors (age, amount of subcutaneous fat, hand volume, or body mass index) that possibly influence peripheral blood flow were found not to influence the results. The observed differences in vascular reactivity toward temperature changes between subjects with a different hormonal status suggest that sex hormones influence finger skin perfusion. PMID- 8458790 TI - Effects of starvation and refeeding on adult male rat diaphragm contractility, fatigue, and fiber types. AB - The effects of 4.5 days of acute starvation, either alone or followed by refeeding (ad libitum), on diaphragm contractility, fatigue, and fiber types were studied in male rats. Contractility and fatigue resistance indexes were measured in an in vitro costal diaphragm strip preparation with direct stimulation at 37 degrees C. Compared with controls, starvation produced a 28 +/- 1% (P < 0.001) reduction in body weight and an 18 +/- 4% (P < 0.001) reduction in costal diaphragm weight. Twitch and tetanic tensions (normalized for weight or cross sectional area) were not reduced by starvation. Starvation produced significant increases in fatigue resistance indexes after a 5-Hz stimulation paradigm but not after a 100-Hz paradigm, supporting the hypothesis that fatigue resistance is dependent on the energy demand of a given paradigm. The proportions of type I and type II fibers were similar between diaphragms of starved and control rats, but the cross-sectional area of type II fibers decreased significantly by 18 +/- 7% (P < 0.01). Thus, despite the significant decrease in diaphragm weight after starvation, contractility was preserved and fatigue resistance was increased (low output paradigm). This is consistent with the decrease in type II fiber area. Refeeding restored all parameters so that there were no longer significant differences in body or diaphragm weight, contractility, fatigue, or fiber types. PMID- 8458791 TI - Adaptations in the elbow flexors of elderly males after heavy-resistance training. AB - The structural and functional characteristics of the elbow flexors in five elderly males were studied before and after 12 wk of heavy-resistance training. Muscle volume and cross-sectional area of two of the elbow flexor (biceps brachii and brachialis) muscles were determined by magnetic resonance imaging. Mean muscle fiber area, percent fiber distribution, and collagen and noncontractile tissue densities were determined on histological sections from needle biopsies. Isokinetic strength of the elbow flexors was measured at velocities between 60 and 300 degrees/s. Muscle volume and cross-sectional area of the biceps brachii and brachialis significantly increased by 13.9 and 22.6%, respectively, after the training program. A preferential hypertrophy of type II fibers (37.2%) was observed. Significant increases in peak torque were observed at all the tested velocities. The amount of work a subject could perform during a 25-repetition test at 240 degrees/s increased by 41% after training. These results demonstrate that the skeletal muscles of elderly individuals can adapt to heavy-resistance exercise and do so by increases in both muscle size and strength. PMID- 8458792 TI - Cardiovascular responses in black and white males during exercise. AB - Previous investigations have shown blacks to have a significantly lower resting heart rate (HR) compared with whites. Our purpose was to determine if this difference exists during submaximal exercise and to compare other cardiovascular responses during submaximal exercise in black and white males. Sixteen black and 16 white males matched on age, body surface area, and maximal O2 consumption exercised at 0, 50, and 100 W on a cycle ergometer. HR, O2 consumption, and cardiac output via CO2 rebreathing were measured at rest and at each work rate. Stroke volume was then calculated. O2 consumption was not significantly different between blacks and whites at rest or at work rates of 0, 50, or 100 W. Cardiac output increased from rest with 0, 50, and 100 W work for both blacks and whites (6.1 to 13.0, 14.4, and 16.9 l/min and 5.7 to 12.2, 14.3, and 16.3 l/min, respectively). The differences in cardiac output between blacks and whites at rest and all work rates were not statistically significant. At rest and work rates of 0, 50, and 100 W, HR was significantly lower in blacks compared with whites (71, 99, 108, and 119 beats/min vs. 80, 107, 114, and 127 beats/min, respectively). The lower HR in blacks compared with whites was accompanied by a trend toward a higher stroke volume at rest and work rates of 0, 50, and 100 W (85.2, 130.3, 134.7, and 142.9 ml vs. 72.5, 114.9, 126.4, and 127.4 ml, respectively). No differences in resting blood pressures were found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458793 TI - Medullary respiratory neuronal activity during augmented breaths in intact unanesthetized cats. AB - In intact unanesthetized cats, we studied the behavior of five medullary respiratory cell types during augmented breaths: 1) decrementing, 2) augmenting, and 3) late-onset inspiratory cells and 4) decrementing and 5) augmenting expiratory cells. Certain features of their behavior were inconsistent with either their proposed role in rhythmogenesis or the proposed nature of augmented breaths. For example, decrementing inspiratory cells switched to an augmenting pattern during the second part of the augmented breath. This behavior is inconsistent with mechanisms proposed to account for their decrementing pattern and with their postulated inhibitory actions on augmenting inspiratory cells, which are intensely active at the same time. In addition, augmenting expiratory cells discharged intensely at the end of inspiration and then throughout expiration, indicating that their discharge profiles (and, therefore, their inhibitory actions) are more labile than previously assumed. The behavior of inspiratory cells gave mixed evidence of the idea that the augmented breath comprises two inspiratory phases: decrementing and late-onset inspiratory cells discharged in two bursts during the inspiratory phase, but other inspiratory cells discharged without interruption throughout it. These results reveal that current theories do not account for the behavior of medullary respiratory cells during augmented breaths. PMID- 8458794 TI - Age-related differences in body composition by hydrodensitometry and dual-energy X-ray absorptiometry. AB - To determine whether percent body fat (%BF) is overestimated in older people by hydrodensitometry (HD) because of an age-related decrease in bone mineral content (BMC), body composition of 113 women and 72 men (21-81 yr) was assessed by HD and dual-energy X-ray absorptiometry (DEXA). DEXA provides an estimate of %BF adjusted for differences in BMC. HD %BF and DEXA %BF were not different in young people [21-39 yr; 17.6 +/- 6.4 (SD) vs. 17.6 +/- 7.2%, NS], were slightly, but significantly, different in middle-aged people (40-59 yr; 25.5 +/- 6.4 vs. 24.1 +/- 6.7%, P < 0.05), and showed the largest disparity in older people (> or = 60 yr; 34.9 +/- 7.9 vs. 30.8 +/- 8.7%, P < 0.05). The discrepancy in older people was apparently not due to mineral loss, however, inasmuch as correction of HD %BF for variance in BMC as a fraction of fat-free mass resulted in only small adjustments (approximately 1%) of %BF. Assessment of DEXA %BF was further evaluated in nine subjects with packets of lard (2-3 kg) overlying either the thigh or the trunk region. Only 55% of the exogenous fat was identified as fat when it was in the trunk region compared with 96% when it was positioned over the legs. These data suggest that the age-related increase in upper body adipose tissue is underestimated by DEXA. PMID- 8458795 TI - Training cessation does not alter GLUT-4 protein levels in human skeletal muscle. AB - The purpose of this study was to determine whether short-term training cessation resulted in reduced GLUT-4 protein levels. Endurance- (n = 12, ET) and strength trained (n = 12) individuals (ST) were examined before and after 14 days of training withdrawal. GLUT-4 content was determined from muscle biopsy samples of the gastrocnemius in ET and the vastus lateralis in ST. Insulin sensitivity (oral glucose tolerance test) was significantly (P < 0.05) reduced in ET and ST with training cessation. GLUT-4 content was unaltered (P > 0.05) in both groups (92 and 100% of trained values for ET and ST, respectively). In ET, citrate synthase activity decreased significantly (P < 0.05) with training withdrawal (41.0 +/- 3.6 vs. 30.6 +/- 2.8 mumol.g-1.min-1); in ST no change was evident. The decrement in insulin sensitivity with the cessation of endurance- or resistance-oriented activity is therefore not associated with a reduction in GLUT-4 protein content. Muscle oxidative capacity and GLUT-4 content do not coincide with the removal of endurance training. PMID- 8458796 TI - Enhanced gluconeogenesis from lactate in perfused livers after endurance training. AB - The effects of endurance training (running 90 min/day at 30 m/min, 10% grade) on hepatic gluconeogenesis were studied in 24-h-fasted rats with use of the isolated liver perfusion technique. After isolation, the liver was perfused (single pass) for 30 min with Krebs-Henseleit bicarbonate buffer and fresh bovine erythrocytes (hematocrit 22-24%) with no added substrate. Subsequent to the "washout" period, the reservoir was elevated with various concentrations of lactate and [U 14C]lactate (10,000 dpm/ml) to assess hepatic glucose production. Relative flow rates were not significantly different between trained (1.94 +/- 0.05 ml/g liver) and control livers (1.91 +/- 0.05 ml/g liver). Furthermore, no significant differences were observed in perfusate pH, hematocrit, bile production, or serum alanine aminotransferase effluxing from trained or control livers. At saturating arterial lactate concentrations (> 2 mM), the maximal rate (Vmax) for hepatic glucose production was significantly higher for trained (0.91 +/- 0.04 mumol.min 1 x g liver-1) than for control livers (0.73 +/- 0.02 mumol.min-1 x g liver-1). That this reflected increased gluconeogenesis is supported by a significant elevation in the Vmax for [14C]glucose production from trained (13,150 +/- 578 dpm.min-1 x g liver-1) compared with control livers (10,712 +/- 505 dpm.min-1 x g liver-1). Significant increases were also observed in the Vmax for lactate uptake (25%), O2 consumption (19%), and 14CO2 production (23%) from endurance-trained livers. The Km for hepatic glucose output, approximately 1.05 mM lactate, was unchanged after endurance training. These findings demonstrate that chronic physical activity results in an elevated capacity for hepatic gluconeogenesis, as assessed in situ at saturating lactate concentrations. PMID- 8458797 TI - Ventilatory work and oxygen consumption during exercise and hyperventilation. AB - The work of breathing (WB), and thus the energy requirement of the respiratory muscles, is increased any time minute ventilation (VE) is elevated, by either exercise or voluntary hyperventilation. Respiratory muscle O2 consumption (VRMO2) in humans has generally been estimated by having subjects breathe at a level comparable to that during exercise while the change in O2 consumption (VO2) is measured. The difference between VO2 at rest and during hyperventilation is attributed to the respiratory muscles and is assumed to be similar to VRMO2 during exercise at the same VE. However, it has been suggested that WB differs between exercise and hyperventilation and that WB during exercise is lower than during hyperventilation at the same VE. In this study we measured WB during exercise and hyperventilation and from these measurements estimated VRMO2. WB, VE, and VO2 were measured in five male subjects during rest and during exercise or hyperventilation at levels of VE ranging from 30 to 130 l/min. VE/WB relationship was determined for both hyperventilation and exercise. Multiple regression analysis showed that the shape of the two curves was different (P < 0.0001), with WB at high levels of VE being < or = 25% higher in hyperventilation than in exercise. In a second study in which frequency, tidal volume, and duty cycle were controlled as well as VE, there was no difference in WB between exercise and hyperventilation. VO2 was significantly correlated with WB, and the estimated VRMO2 did not increase as a fraction of total VO2 as exercise intensity rose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458798 TI - Cerebral cortical evoked potentials elicited by cat intercostal muscle mechanoreceptors. AB - Intercostal muscle afferents discharge in response to changes in intercostal muscle mechanics and have spinal and brain stem projections. It was hypothesized that intercostal muscle mechanoreceptors also project to the sensorimotor cortex. In cats, the proximal muscle branch of an intercostal nerve was used for electrical stimulation. The mechanical stimulation was stretch of an isolated intercostal space. The sensorimotor cortex was mapped with a surface ball electrode. Primary cortical evoked potentials (CEP) were found in area 3a of the sensorimotor cortex with mechanical and electrical stimulation. The CEP was elicited with the smallest stretch amplitude used, 50 microns. The CEP response showed little increase beyond 300-microns stretch. The CEP elicited by 50-microns stretch suggests an initial cortical activation by intercostal muscle spindles. The minimal increase in CEP amplitude with stretch > 300 microns suggests that the CEP response is primarily due to muscle spindle recruitment. The increase in amplitude beyond this stretch may be due to recruitment of tendon organs. These results demonstrate a short-latency projection of intercostal muscle mechanoreceptors to the sensorimotor region of the cerebral cortex. This cortical activation may be involved in respiratory sensations and/or transcortical reflex responses to changes in respiratory muscle mechanics. PMID- 8458799 TI - Ventilatory response to moderate hypoxia in awake chemodenervated cats. AB - In humans and cats the ventilatory response to 30 min of moderate hypoxia (arterial PO2 40-55 Torr) is biphasic: ventilation increases sharply for the first 5 min and then declines. In humans there is evidence that the decline is dependent on the initial increase. We therefore examined ventilatory responses to moderate isocapnic hypoxia in awake cats with and without carotid body denervation. Cats underwent denervation or a sham operation. Then they were studied in a Drorbaugh-Fenn plethysmograph while ventilation, arterial PO2, and end-tidal PO2 and PCO2 were measured. Three sham-operated and four denervated cats were studied with room air as the control. Sham animals demonstrated a biphasic response: ventilation rose to 211% of control at 5 min and fell to 114% of control at 25 min. Denervated animals showed neither the initial increase nor the subsequent decrease in ventilation. Three sham-operated and three denervated cats were studied with 2% CO2 added to the inspirate. Results were similar: intact cats showed a biphasic response to hypoxia, whereas denervated cats showed neither an increase nor a decrease in ventilation. Preliminary experiments showed that hypoxia was not associated with changes in CO2 output or systemic blood pressure in either denervated or intact animals. We conclude that depression of ventilation does not occur in awake denervated cats in response to moderate hypoxia and that the decline in ventilation that occurs in intact cats is in some way dependent on peripheral chemoreceptor output. PMID- 8458800 TI - Reflex bronchodilation produced by phasic ventilation of the lungs. AB - The primary purpose of this work was to demonstrate whether oscillation of tracheal pressure in the range of normal breathing frequencies is more effective than static lung inflation in producing reflex bronchodilation. Secondarily, studies were conducted to determine a single factor that would integrate the reflex bronchodilator effects of frequency and tidal volume. Dogs were anesthetized and placed on cardiopulmonary bypass. After tracheal tone had been reflexly enhanced by chemoreceptor stimulation, oscillatory patterns of ventilation were produced around static pressure lung inflations of approximately 5.0 mmHg. The reflex bronchodilation produced by oscillation of lung volume was compared with that produced by static pressure lung inflation. Reflex bronchodilation produced by oscillation of lung volume was greater than that produced by static pressure inflation of the lungs and was strongly related to the maximum first time derivative of pressure (dP/dt, mmHg/s) observed, irrespective of whether the changes in the maximum dP/dt were produced by changes in the frequency or amplitude of the oscillations of tracheal pressure. PMID- 8458801 TI - Appearance of airway absorption and exudation tracers in guinea pig tracheobronchial lymph nodes. AB - This study examines the fate of extravasated plasma in inflammatory stimulus challenged large tracheobronchial airways of ketamine-xylazine-anesthetized guinea pigs. Entry of plasma tracers into the airway lumen was determined by a validated noninjurious airway lavage technique. Removal by airway lymphatics was assessed by tracheobronchial lymph node levels of plasma tracers. Mucosal challenges with histamine (5 nmol), bradykinin (5 nmol), capsaicin (0.4 nmol), or allergen (ovalbumin, 3 pmol) increased the appearance of a plasma tracer (131I labeled albumin previously injected intravenously) in the airway lumen within 10 min (10-20 times control; P < 0.001), whereas the contractile agent carbachol (8 nmol) was without exudative effect. The mediators were without effect, and capsaicin and allergen only slightly increased the lymph node level of plasma exudation tracer (1.5 times control; P < 0.05). Hence, removal via the lymphatic route of plasma macromolecules may be negligible in the acute and postacute phases of an airway exudation response. Experiments were also carried out with luminally applied macromolecular tracers. These were absorbed from the mucosal surface into the circulation, but a small portion was also transported to the lymph nodes, demonstrating the interconnections between the mucosa and the sampled nodes. Only capsaicin produced an increased node level of absorption tracer. Immunohistochemistry showed that the tracheobronchial tissue and lymph nodes are endowed with nerve fibers containing substance P, the release of which may have mediated lymph transport, vascular, and exudative effects of capsaicin in the present studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458802 TI - Does body temperature mediate anxiolytic effects of acute exercise? AB - We tested the thermogenic hypothesis that reductions in blood pressure and self reported state anxiety and altered brain electrocortical (electroencephalographic, EEG) activity after acute exercise are due to increased body temperature. Eleven fit [cycle peak O2 consumption (VO2peak) = 57 +/- 5.8 ml.kg-1 x min-1] males (26 +/- 5.8 yr) were randomly assigned to four 20-min conditions in a within-subjects counterbalanced design: 1) thermoneutral (32-35 degrees C) or 2) cold (18-23 degrees C) cycling at 70% VO2peak, 3) passive warm water exposure (39-41 degrees C), and 4) quiet rest (60 dB below ambient; 22 +/- 1 degrees C). All exercise testing was conducted in shoulder-deep water. Esophageal temperature increased equally during thermoneutral cycling (+1.45 +/- 0.05 degrees C) and passive heating (+1.51 +/- 0.06 degrees C), was blunted during cold cycling (+0.40 +/- 0.12 degrees C), and was unchanged at rest. Mean radial arterial pressure (MAP), self-reported state anxiety (State-Trait Anxiety Inventory, STAI), and spontaneous occipital (O1 + O2) and photostimulated temporal (T5 + T6) surface EEG activity (10-20 system) in theta (4-8 Hz), alpha (9-13 Hz), and beta (14-40 Hz) frequency bands were assessed 5 min pre- and 10-15 and 20-25 min postcondition and analyzed in 4- (condition) by-3 (time) repeated measures analysis of variance (P < 0.05). Results showed a condition-by-time interaction for MAP, which decreased from pre- to 15 min postcondition for thermoneutral cycling (81 +/- 2 to 73 +/- 2.7 mmHg) and passive heating (86 +/- 2.5 to 74 +/- 1.4 mmHg) and persisted at 25 min postcondition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458803 TI - Effect of anabolic steroids on new fiber formation and fiber area during stretch overload. AB - The efficacy of anabolic steroid treatment to increase the extent of overload induced new fiber formation and fiber hypertrophy was examined in anterior latissimus dorsi (ALD) muscles of Japanese quails. Adult quails were assigned to a control group (n = 20), which received stretch but no steroid (NS), or a stretch+steroid group (S), which received either nandrolone decanoate (n = 20) or testosterone enanthate (n = 12). Steroids were administered at 4.0 mg.kg body wt 1 x day-1. A weight corresponding to 10% of each bird's body weight was added to the right wing to effect a stretch of the right ALD. Thirty days of stretch overload resulted in a 145.3 and 143.1% increase in total muscle weight of NS and S groups, respectively. Stretch-induced increases in nonmuscle tissue, fiber length, and new fiber formation were not altered by steroid administration. These results indicate that anabolic steroids did not act synergistically to enhance the extent of fiber hypertrophy or new fiber formation after 30 days of stretch overload. PMID- 8458804 TI - In vivo quantitation of carbonic anhydrase and band 3 protein contributions to pulmonary gas exchange. AB - The contributions to pulmonary gas exchange of red blood cell (RBC) membrane band 3 protein HCO3(-)-Cl- exchange and carbonic anhydrase- (CA) catalyzed HCO3- dehydration have never been determined directly in the whole animal. We utilized an experimental and model approach to measure these by analysis of phase III exhaled CO2 and O2 profiles in anesthetized dogs. In this method, we inhibit RBC membrane band 3 protein and cytoplasmic CA in RBCs passing the pulmonary capillaries and lung vascular luminal membrane-bound CA during a single ventilatory cycle. This is achieved with appropriately timed right atrial infusions of 4,4'-dinitrostilbene-2,2'-disulfonate (DNDS) to inhibit band 3 protein, ethoxzolamide (a lipophilic CA inhibitor with rapid membrane penetrance) to inhibit RBC and lung tissue CA, and benzolamide (an extremely hydrophilic CA inhibitor with virtually no penetrance into RBC cytoplasm) to inhibit only lung vascular luminal membrane CA. DNDS caused a 15% reduction in CO2 production (VCO2) without any change in O2 consumption (VO2). The addition of benzolamide to DNDS did not cause any further decrease in VCO2. Inhibition of RBC CA by ethoxzolamide caused a 67% reduction in VCO2 and a 11.5% reduction in VO2. Inhibition of lung vascular CA by benzolamide alone caused no statistically significant changes in either VCO2 or VO2. These results are in general agreement with in vitro data and model calculations. The only exceptions are the higher than predicted effect of RBC CA inhibition on VO2 (Bohr effect) and the lack of any contribution to CO2 transfer in the dog by lung vascular CA with access to plasma as a possible consequence of an endogenous plasma CA inhibitor. PMID- 8458805 TI - Chronically instrumented rat model for hemodynamic studies of both pulmonary and systemic circulations. AB - We developed a chronic rat preparation in which a flow probe is placed around the ascending aorta and arterial catheters are implanted in the systemic and pulmonary circulations. This preparation was used to continuously monitor cardiac output (CO), systemic arterial pressure (Psa), and pulmonary arterial pressure (Ppa). More than 80% of the instrumented animals appeared healthy and continued to gain weight for longer than 2 wk. Stable CO, Psa, and Ppa were observed throughout this period. The effects of angiotensin II and hypoxia on the systemic and pulmonary circulations were studied, and possible adverse effects on the heart of long-term implantation of the flow probe were examined. This rat model provides a physiological small-animal preparation for short- and long-term hemodynamic and therapeutic studies on both the systemic and pulmonary circulations. PMID- 8458806 TI - Respiratory load compensation. I. Role of the cerebrum. AB - This study examines the extent to which the cerebrum and other suprapontine structures modulate the respiratory response to added mechanical resistive loads to breathing. Nine adult cats were anesthetized with thiopental sodium, tracheotomized, and instrumented with diaphragm electromyographic (EMGdi) recording electrodes. Two levels of resistive loads and tracheal occlusion were applied at the onset of inspiration in random order before and after decerebration. The integrated signal of the EMGdi (integral of EMGdi) was used to detect changes in respiratory timing and as an index of respiratory motor drive. The results showed that, compared with intact cats, decerebration did not significantly change baseline values for peak integral of EMGdi, respiratory timing, systemic blood pressure, or arterial blood gases. Although the percent changes in the peak integral of EMGdi elicited by the added loads were still significantly greater than those elicited by unloaded control breaths after decerebration, the magnitude of the responses was significantly attenuated at all load levels compared with the intact preparation. It is concluded that the cerebrum and/or other suprapontine structures provide information that is facilitatory to the respiratory pattern generator with little effect on timing. PMID- 8458807 TI - Lymphatic drainage of hypertonic solution from peritoneal cavity of anesthetized and conscious sheep. AB - Lymphatic drainage of the peritoneal cavity may reduce ultrafiltration in continuous ambulatory peritoneal dialysis. We assessed lymphatic drainage of the peritoneal cavity in sheep under dialysis conditions by cannulation of the relevant lymphatic vessels and compared lymphatic drainage in anesthetized and conscious animals. Lymph was collected from the caudal mediastinal lymph node and the thoracic duct, both of which are involved in the lymphatic drainage of the ovine peritoneal cavity. Volumes of a hypertonic dialysis solution (50 ml/kg 4.25% Dianeal) containing 25 microCi 125I-human serum albumin were instilled into the peritoneal cavity, and lymph flows and the appearance of labeled protein in the lymphatic and vascular compartments were monitored for 6 h. Intraperitoneal pressures increased 4-5 cmH2O above resting levels after infusion of dialysate. On the basis of the appearance of tracer in the lymph, drainage of peritoneal fluid into the caudal lymphatic was calculated to be 3.09 +/- 0.69 and 14.14 +/- 2.86 ml/h in anesthetized and conscious sheep, respectively. Drainage of peritoneal fluid into the thoracic duct preparations was calculated to be 1.32 +/ 0.33 and 14.69 +/- 5.73 ml/h in anesthetized and conscious sheep, respectively. Significant radioactivity was found in the bloodstream, and at least a portion of this was likely contributed by the right lymph duct, which was not cannulated in our experiments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458808 TI - Effects of motor unit losses on strength in older men and women. AB - The influence of age-associated motor unit loss on contractile strength was investigated in a representative sample of healthy, active young and older men and women. In 24 younger subjects (22-38 yr) and 20 older subjects (60-81 yr) spike-triggered averaging was employed to extract a sample of surface-recorded single motor unit action potentials (S-MUAPs) from the biceps brachii and brachialis muscles. The amplitude of the maximum compound muscle action potential of the biceps brachii and brachialis muscles was divided by the mean S-MUAP amplitude to estimate the numbers of motor units present. The maximum isometric twitch contraction (MTC) and maximum voluntary contraction (MVC) of the elbow flexors were also recorded in 18 of the younger subjects and in all older subjects. The estimated numbers of motor units were significantly reduced (47%, P < 0.001) in older subjects with a mean value of 189 +/- 77 compared with a mean of 357 +/- 97 in younger subjects. The sizes of the S-MUAPs, however, were significantly larger in older subjects (23%, P < 0.01). Significant but less marked age-associated reductions in the MTC (33%, P < 0.05) and MVC (33%, P < 0.001) were also found and were similar for both men and women. These results suggest that motor unit losses, even in healthy active individuals, are a primary factor in the age-associated reductions in contractile strength. PMID- 8458809 TI - Autonomic control of heart rate during physical exercise and fractal dimension of heart rate variability. AB - The objectives of the present study were to investigate autonomic nervous system influence on heart rate during physical exercise and to examine the relationship between the fractal component in heart rate variability (HRV) and the system's response. Ten subjects performed incremental exercise on a cycle ergometer, consisting of a 5-min warm-up period followed by a ramp protocol, with work rate increasing at a rate of 2.0 W/min until exhaustion. During exercise, alveolar gas exchange, plasma norepinephrine (NE) and epinephrine (E) responses, and beat-to beat HRV were monitored. HRV data were analyzed by "coarse-graining spectral analysis" (Y. Yamamoto and R. L. Hughson. J. Appl. Physiol. 71: 1143-1150, 1991) to break down their total power (Pt) into harmonic and nonharmonic (fractal) components. The harmonic component was further divided into low-frequency (0.0 0.15 Hz) and high-frequency (0.15-0.8 Hz) components, from which low-frequency and high-frequency power (Pl and Ph, respectively) were calculated. Parasympathetic (PNS) and sympathetic (SNS) nervous system activity indicators were evaluated by Ph/Pt and Pl/Ph, respectively. From the fractal component, the fractal dimension (DF) and the spectral exponent (beta) were calculated. The PNS indicator decreased significantly (P < 0.05) when exercise intensity exceeded 50% of peak oxygen uptake (VO2 peak). Conversely, the SNS indicator initially increased at 50-60% VO2peak (P < 0.05) and further increased significantly (P < 0.05) at > 60% VO2peak when there were also more pronounced increases in NE and E.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458810 TI - Acute hormonal responses to two different fatiguing heavy-resistance protocols in male athletes. AB - To examine endogenous hormonal responses to heavy-resistance exercise, ten male strength athletes performed two fatiguing but different types of sessions on separate days. In session A the loads for the leg extensor muscles in the squat lift exercise were maximal so that the subjects performed 20 sets at 1 repetition maximum (RM) (20 x 1 RM x 100%), whereas during session B the loads were submaximal (70%) but the subjects performed each of the 10 sets until the RM (i.e., 10 repetitions/set or 10 x 10 x 70%). The recovery time between the sets was always 3 min. A decrease of 10.3 +/- 4.7% (P < 0.001) occurred in the squat lift in 1 RM during session A, whereas session B led to a decrease of 24.6 +/- 18.9% (P < 0.001) in 10 RM. Increases in the concentrations of serum total and free testosterone (P < 0.05 and 0.05, respectively), cortisol (P < 0.001), and growth hormone (GH, P < 0.001) were observed during session B, whereas the corresponding changes during session A were statistically insignificant except for the relatively slight increase (P < 0.01) in serum GH level. The significant (P < 0.001) increase in blood lactate concentration during the two sessions correlated significantly (P < 0.01) with the increase in serum GH concentration. The morning values of serum testosterone and free testosterone were significantly (P < 0.05-0.001) lowered on the 1st and 2nd rest days after the sessions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458811 TI - Effect of chronic hypoxia and socioeconomic status on VO2max and anaerobic power of Bolivian boys. AB - The aim of this work was to analyze the effects of altitude and socioeconomic and nutritional status on maximal oxygen uptake (VO2max) and anaerobic power (P) in 11-yr-old Bolivian boys. At both high (HA) (3,600 m) and low (LA) (420 m) altitudes, the boys were divided into high (HA1, n = 23, LA1, n = 48) and low (HA2, n = 44, LA2, n = 30) socioeconomic levels. Anthropometric characteristics, VO2max, and P [maximal P (Pmax) during a force-velocity test and mean P (P) during a 30-s Wingate test] were measured. Results showed that 1) anthropometric parameters were not different between HA1 and LA1 and HA2 and LA2 boys, but HA2 and LA2 boys were two years behind HA1 and LA1 boys in development; 2) VO2max was not different in boys from the same altitude, but at HA VO2max was 10% lower than at LA (HA1 = 37.2 +/- 5.6, HA2 = 38.9 +/- 6.4, LA1 = 42.5 +/- 5.8, LA2 = 42.5 +/- 5.3 ml.min-1 x kg-1 body wt); and 3) Pmax and P were higher in well-nourished than in undernourished boys, but there was no difference in Pmax and P between HA1 and LA1 and HA2 and LA2 boys (HA1 = 6.8 +/- 1.0, HA2 = 5.5 +/- 0.8, LA1 = 7.1 +/- 1.0, LA2 = 5.3 +/- 0.9 W/kg for Pmax; HA1 = 5.2 +/- 0.8, HA2 = 4.5 +/- 0.9, LA1 = 5.2 +/- 0.7, LA2 = 4.0 +/- 0.6 W/kg for P).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458812 TI - Role of vasoconstriction in gravity-nondependent central-peripheral gradient in pulmonary blood flow. AB - To examine the effect of vasoconstriction on the gravity-nondependent distribution of pulmonary blood flow, albumin macroaggregates labeled with either 99mTc or 111In were injected at end expiration into dogs (anesthetized, supine, and breathing room air spontaneously). The first dose of macroaggregates was injected during baseline conditions and the second during infusion of serotonin or histamine. Five minutes after the second injection, the chest was opened and the lungs were removed, drained of blood, and dried while fully inflated. Single photon emission computed tomography was performed on the dry lungs to map the three-dimensional distribution of activity of the two isotopes. Images of coronal and sagittal slices were displayed. The results showed that changes in vascular muscle tone did not alter pulmonary blood flow distribution. The absolute flow in a central and peripheral region changed in proportion to cardiac output changes, indicating that during vasoconstriction, as during baseline conditions, there was a preferential perfusion to the interior of the lung. Examination of the average flow in the individual coronal slices showed that during serotonin or histamine infusion, the average flow in each slice changed in proportion to change in cardiac output but that the vertical average flow was not affected significantly. These findings are consistent with the notion that resistive properties (length, diameter, branching pattern) of the pulmonary vascular tree are responsible for the central-peripheral gradient. PMID- 8458813 TI - Interaction between CO2 production and ventilation in the hypoxic kitten. AB - We hypothesized that in the hypoxic newborn the drop in metabolic rate, and particularly in CO2 production (VCO2), contributes to the magnitude of the ventilatory response. Experiments were performed on unanesthetized newborn kittens in a warm [28-30 degrees C ambient temperature (Ta)] or cold (20 degrees C) environment. Breathing pattern and gaseous metabolism were measured by the barometric technique and the inflow-outflow O2 and CO2 difference, respectively. At 30 degrees C, hypoxia (10% O2) decreased VCO2 and induced rapid and shallow breathing, with little effect on minute ventilation (VE). Normoxic exposure to 20 degrees C determined a parallel increase in VE and metabolism; at this Ta, hypoxia decreased VCO2 more than at the higher Ta, and the drop in tidal volume (VT) was also proportionally larger; hence, at 20 degrees C, hypoxic VE was markedly below the normoxic values. Despite these changes in breathing pattern, at neither Ta during hypoxia did arterial PCO2 increase above the normoxic value; in fact, arterial PCO2 at 20 degrees C was slightly decreased because of the important drop in VCO2. Exposure to hypoxia with a CO2 load (inspired CO2 = 1, 3, or 5%) did not abolish the hypometabolic response; the hypoxic depressant effect on VT was either unchanged (by 1% CO2), completely offset (by 3% CO2), or reversed (by 5% CO2), with parallel effects on VE. The results are consistent with the hypothesis that in the newborn the level of CO2, by controlling VT, could represent a link between the metabolic and ventilatory responses to acute hypoxia. PMID- 8458814 TI - Skeletal muscle myosin heavy chain composition and resistance training. AB - We recently reported that 19 wk of heavy resistance training caused a decrease in the percentage of type IIb and an increase in the percentage of type IIa fibers as determined by qualitative histochemical analyses of myofibrillar adenosinetriphosphatase activity of biopsies of musculus vastus lateralis (Hather et al. Acta Physiol. Scand. 143: 177-185, 1991). These data were interpreted to suggest that resistance training had caused transformation among the fast-twitch fiber subtypes. To more clearly establish the influence of resistance training on muscle fiber composition, biopsies from the original study were analyzed biochemically for myosin heavy chain (MHC) composition by use of sodium dodecyl sulfate-polyacrylamide gel electrophoresis and histochemically for fiber types by use of myofibrillar adenosinetriphosphatase activity. The results show that after training (n = 13), IIb MHC composition decreased (P < 0.05) from 19 +/- 4 to 7 +/ 1%. IIa MHC, in contrast, increased (P < 0.05) from 48 +/- 3 to 60 +/- 2%. These responses were essentially mirrored by alterations in fiber type distribution. The percentage of type IIb fibers decreased (P < 0.05) from 18 +/- 3 to 1 +/- 1%, whereas the percentage of type IIa fibers increased from 46 +/- 4 to 60 +/- 3% (P < 0.05). Neither I MHC composition nor type I fiber percentage changed with training. The control group (n = 4) showed no changes in MHC composition or fiber type distribution. These results suggest that heavy resistance training alters MHC composition in human skeletal muscle, presumably reflecting a change in genetic expression. PMID- 8458815 TI - Chronic hypoxic pulmonary hypertension in the guinea pig: effect of three levels of hypoxia. AB - Chronic hypoxia [inspiratory PO2 (PIO2) = 76 Torr for 10 days] produces pulmonary hypertension and vascular remodeling in the guinea pig. Increasing the duration of hypoxia from 10 to 21 days does not increase further pulmonary arterial pressure or medial thickening. To see if increasing severity of hypoxia affects the magnitude of pulmonary hypertension and remodeling, we exposed three groups of male Hartley guinea pigs to three levels of normobaric hypoxia for 10 days: PIO2 = 90 (n = 6), 78 (n = 6), and 65 Torr (n = 5). Pulmonary arterial pressure increased from 14 +/- 1 (+/- SE, n = 7) in room air to 23 +/- 3 mmHg when PIO2 = 90 Torr (P < 0.05). Pulmonary arterial pressure was slightly higher when PIO2 = 78 or 65 Torr (25 +/- 1 and 26 +/- 1 mmHg, respectively) but did not reach statistical significance vs. PIO2 = 90 Torr. Total pulmonary vascular resistance increased from 0.049 +/- 0.004 in room air to between 0.084 +/- 0.006 and 0.101 +/- 0.003 mmHg.min.kg.ml-1 (P < 0.05) in the three hypoxic groups; again there was no difference in total pulmonary vascular resistance among hypoxic groups. Medial thickness of alveolar duct and terminal bronchiole arteries increased with hypoxia, but there was no significant difference among the hypoxic groups. The percentage of intra-acinar vessels with thick walls (a measure of muscular extension) increased when PIO2 = 78 Torr and nearly doubled when PIO2 = 65 Torr in comparison to control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458816 TI - Comparison of mathematical and mechanical models of pressure-controlled ventilation. AB - Recent evidence that volume-cycled mechanical ventilation may itself produce lung injury has focused clinical attention on the pressure waveform applied to the respiratory system. There has been an increasing use of pressure-controlled ventilation (PCV), because it limits peak cycling pressure and provides a decelerating flow profile that may improve gas exchange. In this mode, however, the relationships are of machine adjustments to ventilation and alveolar pressure are not straightforward. Consequently, setting selection remains largely an empirical process. In previous work, we developed a biexponential model of PCV that provides a conceptual framework for understanding these interactions (J. Appl. Physiol. 67: 1081-1092, 1989). We tested the validity of this mathematical model in a single-compartment analogue of the respiratory system across wide ranges of clinician-set variables (frequency, duty cycle, applied pressure) and impedance conditions (inspiratory and expiratory resistance and system compliance). Our data confirm the quantitative validity of the proposed model when approximately rectilinear waves of pressure are applied and appropriate values for impedance are utilized. Despite a fixed-circuit configuration, however, resistance proved to be a function of each clinician-set variable, requiring remeasurement of system impedance as adjustments in these variables were made. With further modification, this model may provide a practical as well as a conceptual basis for understanding minute ventilation and alveolar pressure fluctuations during PCV in the clinical setting. PMID- 8458817 TI - Chronic stimulation-induced changes in mitochondria and performance in rat skeletal muscle. AB - Chronic low-frequency (10-Hz) electrical stimulation was used to investigate mitochondrial biogenesis in rat tibialis anterior muscle. Succinate dehydrogenase and citrate synthase were used as mitochondrial enzymes, and cardiolipin (CL) was used as a phospholipid index of the inner membrane. Stimulation was via the peroneal nerve (24 h/day) for 1, 2, 3, 5, 7, 10, 14, 21, and 28 days (n = 3-9 rats/day). After each period, endurance performance was evaluated in situ. The contralateral side (CON) served as control nonstimulated muscle. Endurance performance gradually improved after 5 days of stimulation to approximately twofold higher than CON muscle beyond 10 days. Succinate dehydrogenase activity rose to 2.4-fold above CON muscle (4.8 +/- 0.2 U/g; n = 54) by 10 days (half time = 6.1 days) and then remained constant. Citrate synthase demonstrated a similar change. The improved performance with stimulation was correlated (r = 0.61, P < 0.05) to these increases in enzyme activities. CL concentration increased from CON (0.35 +/- 0.02 mumol/g; n = 30) to 3.6- and 3.8-fold above CON at 10 and 14 days (half time = 4.2 days). This increase in CL was greater (P < 0.05) than for either enzyme during the same period. These data are consistent with a model of mitochondrial membrane biogenesis in which enzyme proteins are inserted into a presynthesized lipid bilayer. PMID- 8458818 TI - Direct measurement of capillary blood pressure in the human lip. AB - In this study, we developed and tested a new procedure for measuring microcirculatory blood pressures above heart level in humans. Capillary and postcapillary venule blood pressures were measured directly in 13 human subjects by use of the servo-nulling micropressure technique adapted for micropuncture of lip capillaries. Pressure waveforms were recorded in 40 separate capillary vessels and 14 separate postcapillary venules over periods ranging from 5 to 64 s. Localization and determination of capillary and postcapillary vessels were ascertained anatomically before pressure measurements. Capillary pressure was 33.2 +/- 1.5 (SE) mmHg in lips of subjects seated upright. Repeated micropunctures of the same vessel gave an average coefficient of variation of 0.072. Postcapillary venule pressure was 18.9 +/- 1.6 mmHg. This procedure produces a direct and reproducible means of measuring microvascular blood pressures in a vascular bed above heart level in humans. PMID- 8458819 TI - Intrapulmonary shunt in excised dog lobes: comparison of oxygen and inert gas methods. AB - We evaluated the contribution of measurement errors in PO2 to the discrepancy between the intrapulmonary shunt values simultaneously obtained by the conventional O2 method (O2-shunt) and the multiple inert gas elimination technique (IG-shunt). Excised left lower lobes of dogs were perfused at a constant flow and ventilated at constant volume. Variable degrees of intrapulmonary shunt were created by O2 absorption while the lobes were collapsed. IG-shunt ranged from 0 to 66%. Although the O2-shunt and IG-shunt values correlated well (r = 0.97), the slope was only 0.74 and the regression line crossed the line of identity at 12% IG-shunt. The gas-to-blood ratio of the oxygen electrode was constant over the range 80-687 Torr and therefore did not seem to be an important factor in the shunt discrepancy. Errors due to nonlinearity of the O2 electrode also had only a minor effect. However, PO2 history of the electrode just before injection of blood samples into the cuvette had a profound and complex effect on the measured PO2. We conclude that PO2 electrode hysteresis can be a major factor in the wide variability of PO2 measurements and could account for most of the differences between our O2-shunt and IG-shunt data. PMID- 8458820 TI - Calculation of venoarterial CO2 concentration difference. AB - Quantitative relationships in CO2 transport and exchange processes were combined for use as the basic components of an original mathematical model for the calculation of venoarterial blood CO2 concentration difference (v-aDCO2). This is calculated as the sum of the increment in CO2 concentration (CCO2) related to the increase in CO2 tension (delta P) from arterial to venous value at constant O2 saturation (delta CCO2/delta P) and of the increment in CO2 concentration related to the decrease in O2 saturation (delta S) from arterial to venous value at constant CO2 tension (delta CCO2/delta S). The newly developed relationships correlated well with the experimental data from which they were derived (r2 = 0.94-0.99). The results provided by the model compared remarkably well with the results of previously published measurements (r2 = 0.96-0.99). This new model allows one to overcome some of the limitations implicit in previously available methods and provides a useful tool for the assessment and monitoring of hemodynamic, metabolic, and O2-CO2 exchange patterns in whole body and regional vascular beds. PMID- 8458821 TI - Effects of an antioxidant vitamin mixture on lipid peroxidation at rest and postexercise. AB - We studied the effects of ingesting an antioxidant vitamin mixture for 6 wk on breath pentane and serum malondialdehyde (MDA) levels before and after exercise. Twenty young (mean age 25.0 +/- 2.9 yr) healthy males were randomly assigned to either an antioxidant vitamin group (daily doses of 592 mg of alpha-tocopherol equivalents, 1,000 mg of ascorbic acid, and 30 mg of beta-carotene) or a placebo group. Exercise consisted of 30 min of treadmill running at 60% of maximal O2 consumption (VO2max) followed by 5 min of running at a pace that elicited approximately 90% of VO2max. Blood and breath samples were collected immediately after the two exercise bouts. The antioxidant supplement did not prevent the exercise-induced increase in lipid peroxidation, as reflected by the rate of pentane production and the increase in serum MDA concentration. However, ingestion of the antioxidant vitamins did result in significantly lower resting and postexercise levels of expired pentane and serum MDA. We conclude that taking ascorbate, alpha-tocopherol, and beta-carotene in the amounts used in this study serves to lower markers of lipid peroxidation at rest and after exercise but does not prevent the exercise-induced increase in oxidative stress. PMID- 8458822 TI - Investigating changes in muscle occurring in association with high-intensity exercise. PMID- 8458823 TI - Nebulized salbutamol (albuterol): systemic absorption could be important in achieving bronchodilatation. PMID- 8458824 TI - Are current pediatric dose recommendations for intravenous theophylline appropriate? AB - Theophylline, a first-line antiasthma drug, is often associated with severe toxicity even when taken in the recommended schedule. Theophylline toxicity has been associated with upper respiratory tract infections (URTI) due to reduced total-body clearance of theophylline. Some researchers believe this inhibition stems from a direct effect of viruses, but others postulate it is a result of the fever. We examined whether current theophylline dose recommendations are appropriate for children with acute asthma with a concurrent URTI. We also wished to elucidate whether the viral infection or the fever inhibits theophylline clearance. A total of 2254 medical records of asthmatic children admitted to The Hospital for Sick Children in Toronto were reviewed between 1987 and 1990. Clearance rate was calculated as the ratio between the infused dose rate and measured steady-state concentrations. Subsequently, these clearance rates were used to calculate steady-state concentrations that would be achieved by the recommended dose rates of theophylline. Reduced theophylline clearance was associated with the presence of URTI (p = 0.029) but not fever. Age correlated significantly with theophylline clearance (p = 0.027). If these children were to receive the recommended intravenous dose rate of theophylline, two-thirds of them would achieve steady-state serum concentrations above 15 mg/L, and one-third would achieve concentrations above 20 mg/L. Reevaluation of the present recommended theophylline dose rate is needed, as the majority of children requiring intravenous theophylline have a concurrent URTI with compromised total body clearance. A correction factor of 60% is recommended to adjust the dose rate during an URTI. If utilized by prescribing physicians, it may reduce theophylline toxicity during an URTI episode. PMID- 8458825 TI - A case report of a seizure disorder presenting as respiratory distress. PMID- 8458826 TI - Three cases of adolescent near-fatal asthma: what do they have in common? PMID- 8458827 TI - Allergy diagnosis: La Jolla Village, California, February 6-9, 1992, sponsored by UC&D. PMID- 8458828 TI - Is asthma really different in the elderly patient? PMID- 8458829 TI - Asthma in the elderly. PMID- 8458830 TI - Eubacterial components similar to small nuclear ribonucleoproteins: identification of immunoprecipitable proteins and capped RNAs in a cyanobacterium and a gram-positive eubacterium. AB - Small nuclear ribonucleoprotein (snRNP) particles play an important role in the processing of pre-mRNA. snRNPs have been identified immunologically in a variety of cells, but none have ever been observed in prokaryotic systems. This report provides the first evidence for the presence of snRNP-like components in two types of prokaryotic cells: those of the cyanobacterium Synechococcus leopoliensis and those of the gram-positive eubacterium Bacillus subtilis. These components consist of snRNP-immunoreactive proteins and RNAs, including some with the snRNP-unique 5' m2,2,7G (m3G) cap. Immunoreactivity was determined by immunoprecipitation procedures, with either antinuclear-antibody-positive (RNP- and Sm-monospecific) patient sera or a m3G monoclonal antibody, with radiolabelled cell extracts that were preadsorbed with antinuclear-antibody negative sera. S. leopoliensis immunoprecipitates showed the presence of high molecular-mass proteins (14 to 70 kDa) and RNAs (138 to 243 nucleotides) that are analogous in size to proteins and RNAs found in human (HEp-2) cell immunoprecipitates but absent in Escherichia coli immunoprecipitates. Thin-layer chromatography of S. leopoliensis immunoprecipitates confirmed the presence of a capped nucleotide similar to a capped nucleotide in HEp-2 immunoprecipitates; no such nucleotide was observed in E. coli immunoprecipitates. Immunoreactive RNAs (117-170 nucleotides) were identified in a second eubacterium, B. subtilis, as well. This work suggests that snRNPs or their evolutionary predecessors predate the emergence of eukaryotic cells. PMID- 8458831 TI - Physiological analysis of mutants indicates involvement of the Saccharomyces cerevisiae GPI-anchored protein gp115 in morphogenesis and cell separation. AB - This paper reports a phenotypic characterization of ggp1 mutants. The cloned GGP1 (GAS1) gene, which encodes a major GPI-anchored glycoprotein (gp115) of Saccharomyces cerevisiae of unknown function, was used to direct the inactivation of the chromosomal gene in haploid and diploid strains by gene replacement. The analysis of the null mutants reveals a reduction in the growth rate of 15 to 40%. Cells are round, with more than one bud, and extensively vacuolized. In the stationary phase, mutant cells are very large, arrest with a high percentage of budded cells (about 54 and 70% for haploid and diploid null mutants, respectively, in comparison with about 10 to 13% for control cells), and have reduced viability. The observed phenotype suggests defects in cell separation. Flow cytometric analysis of DNA reveals an increase in the fraction of cells in the G2+M+G1* compartment during exponential growth. Conjugation and sporulation are not affected. The exocellular location of gp115 led us to examine cell wall properties. Cell wall and septum ultrastructure of abnormally budded cells was analyzed by electron microscopy analysis, and no appreciable differences from wild-type cells were found. Microscopic analysis revealed an increase in chitin content and delocalization. In comparison with control cells, ggp1 null mutants are shown to be resistant to Zymolyase during the exponential growth phase. A fivefold overexpression of gp115 does not bring about any effects on cell growth parameters and cell wall properties. PMID- 8458832 TI - Organization of a Clostridium thermocellum gene cluster encoding the cellulosomal scaffolding protein CipA and a protein possibly involved in attachment of the cellulosome to the cell surface. AB - The nucleotide sequence was determined for a 9.4-kb region of Clostridium thermocellum DNA extending from the 3' end of the gene (now termed cipA), encoding the S1/SL component of the cellulosome. Three open reading frames (ORFs) belonging to two operons were detected. They encoded polypeptides of 1,664, 688, and 447 residues, termed ORF1p, ORF2p, and ORF3p, respectively. The COOH-terminal regions of the three polypeptides were highly similar and contained three reiterated segments of 60 to 70 residues each. Similar segments have been found at the NH2 terminus of the S-layer proteins of Bacillus brevis and Acetogenium kivui, suggesting that ORF1p, ORF2p, and ORF3p might also be located on the cell surface. Otherwise, the sequence of ORF1p and ORF2p gave little clue concerning their potential function. However, the NH2-terminal region of ORF3p was similar to the reiterated domains previously identified in CipA as receptors involved in binding the duplicated segment of 22 amino acids present in catalytic subunits of the cellulosome. Indeed, it was found previously that ORF3p binds 125I-labeled endoglucanase CelD containing the duplicated segment (T. Fujino, P. Beguin, and J.-P. Aubert, FEMS Microbiol. Lett. 94:165-170, 1992). These findings suggest that ORF3p might serve as an anchoring factor for the cellulosome on the cell surface by binding the duplicated segment that is present at the COOH end of CipA. PMID- 8458833 TI - Cellulose-binding polypeptides from Cellulomonas fimi: endoglucanase D (CenD), a family A beta-1,4-glucanase. AB - Five cellulose-binding polypeptides were detected in Cellulomonas fimi culture supernatants. Two of them are CenA and CenB, endo-beta-1,4-glucanases which have been characterized previously; the other three were previously uncharacterized polypeptides with apparent molecular masses of 120, 95, and 75 kDa. The 75-kDa cellulose-binding protein was designated endoglucanase D (CenD). The cenD gene was cloned and sequenced. It encodes a polypeptide of 747 amino acids. Mature CenD is 708 amino acids long and has a predicted molecular mass of 74,982 Da. Analysis of the predicted amino acid sequence of CenD shows that the enzyme comprises four domains which are separated by short linker polypeptides: an N terminal catalytic domain of 405 amino acids, two repeated sequences of 95 amino acids each, and a C-terminal domain of 105 amino acids which is > 50% identical to the sequences of cellulose-binding domains in Cex, CenA, and CenB from C. fimi. Amino acid sequence comparison placed the catalytic domain of CenD in family A, subtype 1, of beta-1,4-glycanases. The repeated sequences are more than 40% identical to the sequences of three repeats in CenB and are related to the repeats of fibronectin type III. CenD hydrolyzed the beta-1,4-glucosidic bond with retention of anomeric configuration. The activities of CenD towards various cellulosic substrates were quite different from those of CenA and CenB. PMID- 8458834 TI - The sigma B-dependent promoter of the Bacillus subtilis sigB operon is induced by heat shock. AB - sigma B, a secondary sigma factor of Bacillus subtilis, was found to increase 5- to 10-fold when cultures were shifted from 37 to 48 degrees C. Western blot (immunoblot) analyses, in which monoclonal antibodies specific for the sigB operon products RsbV, RsbW, and sigma B were used to probe extracts from wild type and mutant B. subtilis strains, revealed that all three proteins increased coordinately after heat shock and that this increase was dependent on sigma B but not RsbV, a positive regulator normally essential for sigma B-dependent sigB expression. Nuclease protection experiments of RNA synthesized after heat shock supported the notion that the shift to 48 degrees C enhanced transcription from the sigB operon's sigma B-dependent promoter. The level of mRNA initiating at the sigma B-dependent ctc promoter was also seen to increase approximately 5- to 10 fold after heat shock. Pulse-labeling of the proteins synthesized after a shift to 48 degrees C demonstrated that sigB wild-type and mutant strains produced the major heat-inducible proteins in similar amounts; however, at least seven additional proteins were present after the temperature shift in the wild-type strain but absent in the sigB null mutant. Thus, although sigma B is not required for the expression of essential heat shock genes, it is activated by heat shock to elevate its own synthesis and possibly the synthesis of several other heat inducible proteins. PMID- 8458835 TI - Mechanism of silicate binding to the bacterial cell wall in Bacillus subtilis. AB - To investigate the chemical mechanism of silicate binding to the surface of Bacillus subtilis, we chemically modified cell wall carboxylates to reverse their charge by the addition of an ethylenediamine ligand. For up to 9 weeks, mixtures of Si, Al-Fe-Si, and Al-Fe-Si plus toxic heavy metals were reacted with these cells for comparison with control cells and abiotic solutions. In general, more Si and less metal were bound to the chemically modified surfaces, thereby showing the importance of an electropositive charge in cell walls for fine-grain silicate mineral development. The predominant reaction for this development was the initial silicate-to-amine complexation in the peptidoglycan of ethylenediamine modified and control cell walls, although metal ion bridging between electronegative sites and silicate had an additive effect. The binding of silicate to these bacterial surfaces can thus be described as outer sphere complex formation because it occurs through electrostatic interaction. PMID- 8458836 TI - Transmission electron microscopy, scanning tunneling microscopy, and atomic force microscopy of the cell envelope layers of the archaeobacterium Methanospirillum hungatei GP1. AB - Methanospirillum hungatei GP1 possesses paracrystalline cell envelope components including end plugs and a sheath formed from stacked hoops. Both negative-stain transmission electron microscopy (TEM) and scanning tunneling microscopy (STM) distinguished the 2.8-nm repeat on the outer surface of the sheath, while negative-stain TEM alone demonstrated this repeat around the outer circumference of individual hoops. Thin sections revealed a wave-like outer sheath surface, while STM showed the presence of deep grooves that precisely defined the hoop-to hoop boundaries at the waveform nodes. Atomic force microscopy of sheath tubes containing entrapped end plugs emphasized the end plug structure, suggesting that the sheath was malleable enough to collapse over the end plugs and deform to mimic the shape of the underlying structure. High-resolution atomic force microscopy has revised the former idea of end plug structure so that we believe each plug consists of at least four discs, each of which is approximately 3.5 nm thick. PT shadow TEM and STM both demonstrated the 14-nm hexagonal, particulate surface of an end plug, and STM showed the constituent particles to be lobed structures with numerous smaller projections, presumably corresponding to the molecular folding of the particle. PMID- 8458837 TI - Phenotypic revertant mutations of a new OmpR2 mutant (V203Q) of Escherichia coli lie in the envZ gene, which encodes the OmpR kinase. AB - The Escherichia coli ompR2 allele ompR472 contains a valine-to-methionine point mutation at position 203, resulting in an OmpF-constitutive OmpC- outer membrane phenotype. In the present study, OmpR residue V-203 was replaced with glutamine (V203Q mutation), resulting in the same outer membrane phenotype. However, unlike the OmpFc OmpC- phenotype conferred by the OmpR(V203M) mutant protein, the OmpFc OmpC- phenotype produced by the OmpR(V203Q) mutation was suppressed by the envZ11(T247R) allele. Additional suppressors of OmpR(V203Q) were isolated by random mutagenesis. All suppressor mutations were found in the envZ gene and conferred an OmpC+ OmpF- phenotype in the presence of the wild-type ompR. These envZ11-like mutations mapped to a region different from those previously reported and were incapable of suppressing the ompR(V203M) allele. Our results indicate that while methionine or glutamine replacements could cause similar effects on OmpF and OmpC expression, they conferred different abilities on the mutant proteins to be suppressed by envZ. PMID- 8458838 TI - Modulation of the heat shock response by one-carbon metabolism in Escherichia coli. AB - A genetic screen designed to isolate mutants of Escherichia coli W3110 altered in the ability to induce the heat shock response identified a strain unable to induce the heat shock proteins in a rich, defined medium lacking methionine after exposure to 2,4-dinitrophenol. This strain also grew slowly at 28 degrees C and linearly at 42 degrees C in this medium. The abnormal induction of the heat shock proteins and abnormal growth at both high and low temperatures were reversed when methionine was included in the growth medium. The mutation responsible for these phenotypes mapped to the glyA gene, a biosynthetic gene encoding the enzyme that converts serine and tetrahydrofolate to glycine and 5,10 methylenetetrahydrofolate. This reaction is the major source of glycine and one carbon units in the cell. Because fixed one-carbon units, in the form of methionine, allowed mutant cells to induce the heat shock response after exposure to 2,4-dinitrophenol, a one-carbon restriction may be responsible for the phenotypes described above. PMID- 8458839 TI - In vitro activation of ammonia monooxygenase from Nitrosomonas europaea by copper. AB - The effect of copper on the in vivo and in vitro activity of ammonia monooxygenase (AMO) from the nitrifying bacterium Nitrosomonas europaea was investigated. The addition of CuCl2 to cell extracts resulted in 5- to 15-fold stimulation of ammonia-dependent O2 consumption, ammonia-dependent nitrite production, and hydrazine-dependent ethane oxidation. AMO activity was further stimulated in vitro by the presence of stabilizing agents, including serum albumins, spermine, or MgCl2. In contrast, the addition of CuCl2 and stabilizing agents to whole-cell suspensions did not result in any stimulation of AMO activity. The use of the AMO-specific suicide substrate acetylene revealed two populations of AMO in cell extracts. The low, copper-independent (residual) AMO activity was completely inactivated by acetylene in the absence of exogenously added copper. In contrast, the copper-dependent (activable) AMO activity was protected against acetylene inactivation in the absence of copper. However, in the presence of copper both populations of AMO were inactivated by acetylene. [14C]acetylene labelling of the 27-kDa polypeptide of AMO revealed the same extent of label incorporation in both whole cells and optimally copper-stimulated cell extracts. In the absence of copper, the label incorporation in cell extracts was proportional to the level of residual AMO activity. Other metal ions tested, including Zn2+, Co2+, Ni2+, Fe2+, Fe3+, Ca2+, Mg2+, Mn2+, Cr3+, and Ag+, were ineffective at stimulating AMO activity or facilitating the incorporation of 14C label from [14C]acetylene into the 27-kDa polypeptide. On the basis of these results, we propose that loss of AMO activity upon lysis of N. europaea results from the loss of copper from AMO, generating a catalytically inactive, yet stable and activable, form of the enzyme. PMID- 8458840 TI - The acid tolerance response of Salmonella typhimurium involves transient synthesis of key acid shock proteins. AB - Although Salmonella typhimurium prefers neutral-pH environments, it can adapt to survive conditions of severe low-pH stress (pH 3.3). The process, termed the acid tolerance response (ATR), includes two distinct stages. The first stage, called pre-acid shock, is induced at pH 5.8 and involves the production of an inducible pH homeostasis system functional at external pH values below 4.0. The second stage occurs following an acid shock shift to pH 4.5 or below and is called the post-acid shock stage. During this stage of the ATR, 43 acid shock proteins (ASPs) are synthesized. The present data reveal that several ASPs important for pH 3.3 acid tolerance are only transiently produced. Their disappearance after 30 to 40 min of pH 4.4 acid shock coincides with an inability to survive subsequent pH 3.3 acid challenge. Clearly, an essential feature of inducible acid tolerance is an ability to synthesize these key ASPs. The pre-acid shock stage, with its inducible pH homeostasis system, offers the cell an enhanced ability to synthesize ASPs following rapid shifts to conditions below pH 4.0, an external pH that normally prevents ASP synthesis. The data also address possible signals for ASP synthesis. The inducing signal for 22 ASPs appears to be internal acidification, while external pH serves to induce 13 others. Of the 14 transient ASPs, 10 are induced in response to changes in internal pH. Mutations in the fur (ferric uptake regulator) locus that produce an Atr- acid-sensitive phenotype also eliminate induction of six transiently induced ASPs. PMID- 8458841 TI - Analysis of features contributing to activity of the single-stranded origin of Bacillus plasmid pBAA1. AB - The features which contribute to the activity of the single-stranded origin of the Bacillus plasmid pBAA1 were investigated. This origin is contained on a DNA fragment greater than 116 but less than 191 bases in size. There is the potential to form three stem-loop structures within this fragment. Comparison of the sequence of this origin from pBAA1 with the sequence of a homologous fragment from the Bacillus thuringiensis plasmid pGI2 indicates that both the structure and the relative positioning of the predicted stem-loops are important for origin activity. Deletion analysis suggests that it is the structure of stem-loop III which is important, because it can be replaced by a nonrelated dyad element without significant loss of origin activity. Three sequence motifs are conserved between the origins from pBAA1 and pGI2. Mutation of motif 1 leads to attenuation of single-stranded origin activity. A second motif (motif 3) shares significant homology with a group of single-strand initiation (ssi) sites found on plasmids isolated from Escherichia coli, suggesting that it also contributes to single stranded origin activity. Our results also indicate that RNA polymerase is utilized to synthesize the RNA primer at the pBAA1 single-stranded origin and that this origin can function in both Bacillus subtilis and Staphylococcus aureus. PMID- 8458842 TI - Accumulation of bldA-specified tRNA is temporally regulated in Streptomyces coelicolor A3(2). AB - Deletion of the bldA gene of Streptomyces coelicolor A3(2), which encodes the only tRNA for the rare UUA codon, had no obvious effects on primary growth but interfered with aerial mycelium formation and antibiotic production. To investigate the possible regulatory role of bldA, its transcription start point was identified, and time courses were determined for the appearance of its primary transcript, the processing of the primary transcript to give a mature 5' end, and the apparent efficiency of translation of ampC mRNA, which contains multiple UUA codons. The bldA promoter was active at all times, but processing of the 5' end of the primary transcript was comparatively inefficient in young cultures. This may perhaps involve an antisense RNA, evidence of which was provided by promoter probing and in vitro transcription. The presence of low levels of the processed form of the tRNA in young cultures followed by increased abundance in older cultures contrasted with the pattern observed for accumulation of a different, presumably typical tRNA which was approximately equally abundant throughout growth. The increased accumulation of the 5' processed form of bldA tRNA coincided with more-efficient translation of ampC mRNA in older cultures, supporting the hypothesis that in at least some physiological conditions, bldA may have a regulatory influence on events late in growth, such as morphological differentiation and antibiotic production. PMID- 8458843 TI - A gene cluster involved in aerial mycelium formation in Streptomyces griseus encodes proteins similar to the response regulators of two-component regulatory systems and membrane translocators. AB - Mutants of Streptomyces griseus deficient in A-factor production are sporulation negative, since A-factor is an essential hormonal regulator for the induction of morphological and physiological differentiation in this bacterium. A DNA fragment which induced aerial mycelium formation and sporulation in an A-factor-deficient mutant strain, S. griseus HH1, was cloned from this mutant strain. Subcloning experiments and nucleotide sequencing showed that two open reading frames, ORF1 with 656 amino acids and ORF2 with 201 amino acids, were required in order to induce sporulation. The amino acid sequence of ORF1 significantly resembled that of the Escherichia coli HlyB protein, a member of a family of bacterial membrane proteins engaged in ATP-dependent secretion mechanisms. Conserved features of this surface translocator family, such as the transmembrane structure predicted by their hydropathy profiles and the amino acid sequence forming an ATP-binding fold, were also conserved in ORF1. The ORF1 gene appeared to constitute a transcriptional unit with an additional upstream gene encoding ORF3, which was greatly similar to ORF1 in size and amino acid sequence. The other protein, ORF2, showed significant end-to-end homology with the E. coli uhpA product, a regulatory protein for the uptake of sugar phosphates. Like UhpA as a response regulator of a bacterial two-component regulatory system, ORF2 contained a helix turn-helix DNA-binding domain at its COOH-terminal portion and an Asp residue (Asp-54) probably to be phosphorylated at its NH2-terminal portion. An amino acid replacement from Asp-54 to Asn resulted in the loss of the ability of ORF2 to induce sporulation in strain HH1. PMID- 8458844 TI - Restoration of pathogenicity of avirulent Xanthomonas oryzae pv. oryzae and X. campestris pathovars by reciprocal complementation with the hrpXo and hrpXc genes and identification of HrpX function by sequence analyses. AB - The molecular basis of pathogenesis by Xanthomonas oryzae pv. oryzae has been partly elucidated by the identification of a gene, hrpXo, required for bacterial blight on rice. A mutation in hrpXo results in the loss of pathogenicity on rice and the loss of hypersensitivity on nonhosts such as Datura stramonium and radishes. Pathogenicity and its ability to cause the hypersensitive reaction is restored by complementing the mutant with the heterologous hrpXc gene derived from X. campestris pv. campestris. Conversely, hrpXo complements nonpathogenic mutants of X. campestris pv. campestris and X. campetstris pv, armoraciae. Mutants bearing the heterologous hrpX gene are restored in their abilities to cause diseases typical of their chromosomal background and not the hypersensitive reaction on their respective hosts. The hrpXo and hrpXc genes are therefore functionally equivalent, and this functional equivalence extends into X. campestris pv. armoraciae and possibly into other X. campestris pathovars, since this gene is highly conserved among eight other pathovars tested. Sequence analyses of hrpXo revealed an open reading frame of 1,452 bp with a coding capacity for a protein of 52.3 kDa. The protein contains a consensus domain for possible protein myristoylation whose consequence may result in a loss of recognition by host defense and surveillance systems. PMID- 8458845 TI - Global regulation of gene expression in Escherichia coli. AB - Global transcription responses of Escherichia coli to various stimuli or genetic defects were studied by measuring mRNA levels in about 400 segments of the genome. Measuring mRNA levels was done by analyzing hybridization to DNA dot blots made with overlapping lambda clones spanning the genome of E. coli K-12. Conditions examined included isopropyl-beta-D-thiogalactopyranoside (IPTG) induction, heat shock, osmotic shock, starvation for various nutrients, entrance of cells into the stationary phase of growth, anaerobic growth in a tube, growth in the gnotobiotic mouse gut, and effects of pleiotropic mutations rpoH, himA, topA, and crp. Most mapped genes known to be regulated by a particular situation were successfully detected. In addition, many chromosomal regions containing no previously known regulated genes were discovered that responded to various stimuli. This new method for studying globally regulated genetic systems in E. coli combines detection, cloning, and physical mapping of a battery of coregulated genes in one step. PMID- 8458847 TI - Identification of a genetic element (psr) which negatively controls expression of Enterococcus hirae penicillin-binding protein 5. AB - Enterococcus hirae ATCC 9790 produces a penicillin-binding protein (PBP5) of low penicillin affinity which under certain conditions can take over the functions of all the other PBPs. The 7.1-kb EcoRI fragment containing the pbp5 gene of this strain and of two mutants, of which one (E. hirae R40) overproduces PBP5 and the other (E. hirae Rev14) does not produce PBP5, was cloned in pUC18 and sequenced. In the 7.1-kb EcoRI fragment cloned from strain ATCC 9790, an open reading frame (psr) potentially encoding a 19-kDa protein was identified 1 kb upstream of the pbp5 gene. An 87-bp deletion in this element was found in the 7.1-kb EcoRI fragment cloned from strains R40 and Rev14. In addition, several base substitutions were found in the pbp5 genes of strains R40 and Rev14. One of these converted the 42nd codon, TCA, to the stop codon, TAA, in the pbp5 gene of Rev14. Escherichia coli strains were transformed with plasmids carrying the 7.1-kb EcoRI insert or a 2.6-kb HincII insert containing only the pbp5 gene of the three strains. Immunoblotting analysis of proteins expressed by these transformants showed that the 87-bp deletion in psr was associated with the PBP5 overproducer phenotype of strain R40 and the conversion of the TCA codon to the stop codon was associated with the PBP5 nonproducer phenotype of strain Rev14. None of the other nucleotide substitutions had any apparent effect on the level of PBP5 synthesized. PMID- 8458846 TI - Analysis of the promoter and regulatory sequences of an oxygen-regulated bch operon in Rhodobacter capsulatus by site-directed mutagenesis. AB - The biosynthesis of pigments (carotenoids and bacteriochlorophylls) in the photosynthetic bacterium Rhodobacter capsulatus is regulated by the oxygen concentration in the environment. However, the mechanism of this regulation has remained obscure. In this study, transcriptional fusions of the bchCXYZ promoter region to lacZ were used to identify the promoter and regulatory sequences governing transcription of these bacteriochlorophyll biosynthesis genes. The promoter region was identified in vivo by making deletions and site-directed mutations. The 50 bp upstream of the promoter region was shown to be required for the oxygen-dependent transcriptional regulation of bchCXYZ. A previously described palindrome sequence is also likely involved in the regulation. A gel mobility shift assay further defined the interaction of transcription regulators with these DNA sequence elements in vitro and demonstrated that a DNA-protein complex is formed at this promoter region. Since the suggested promoter sequence and the palindrome sequence are found upstream of several other bch and crt operons, these sequences may be responsible for regulating oxygen-dependent pigment biosynthesis at the level of transcription in R. capsulatus. In addition, these cis-acting DNA elements are not found upstream of puh and puf operons, which encode the structural polypeptides of the reaction center and light harvesting I complexes. This observation supports the model of different regulatory mechanism for the pigment biosynthesis enzymes and structural polypeptides required for the production of the photosynthetic apparatus. PMID- 8458848 TI - Di-tripeptides and oligopeptides are taken up via distinct transport mechanisms in Lactococcus lactis. AB - Lactococcus lactis ML3 possesses two different peptide transport systems of which the substrate size restriction and specificity have been determined. The first system is the earlier-described proton motive force-dependent di-tripeptide carrier (E. J. Smid, A. J. M. Driessen, and W. N. Konings, J. Bacteriol. 171:292 298, 1989). The second system is a metabolic energy-dependent oligopeptide transport system which transports peptides of four to at least six amino acid residues. The involvement of a specific oligopeptide transport system in the utilization of tetra-alanine and penta-alanine was established in a mutant of L. lactis MG1363 that was selected on the basis of resistance to toxic analogs of alanine and alanine-containing di- and tripeptides. This mutant is unable to transport alanine, dialanine, and trialanine but still shows uptake of tetra alanine and penta-alanine. The oligopeptide transport system has a lower activity than the di-tripeptide transport system. Uptake of oligopeptides occurs in the absence of a proton motive force and is specifically inhibited by vanadate. The oligopeptide transport system is most likely driven by ATP or a related energy rich, phosphorylated intermediate. PMID- 8458849 TI - A sigma 54 promoter and downstream sequence elements ftr2 and ftr3 are required for regulated expression of divergent transcription units flaN and flbG in Caulobacter crescentus. AB - In this study, we investigated the cis-acting sequences required for transcription of the divergent, cell cycle-regulated flaN and flbG operons of Caulobacter crescentus. Previous work showed that transcription of flbG in vivo depends on a sigma 54 promoter and a sequence element called ftr1 that is located about 100 bp upstream from the transcription start site (D. A. Mullin and A. Newton, J. Bacteriol. 171:3218-3227, 1989). We now show that regulation of flaN transcription in vivo depends on a sigma 54 promoter and two ftr elements located downstream of the transcription start site at +86 (ftr2) and +120 (ftr3). Mutations in or between the conserved elements at -24 and -12 in this sigma 54 promoter reduced or abolished flaN transcription, and one mutation that eliminated flaN expression led to an increased level of flbG transcript. Mutations in ftr2 resulted in greatly reduced levels of flaN transcript but had no noticeable effect on flbG transcript levels. All three mutations constructed in ftr3 resulted in elevated flaN and flbG transcript levels. We conclude that ftr2 is required for positive regulation of flaN, whereas ftr3 appears to play a negative regulatory role in flaN and flbG expression. To explain the coordinated positive activation and negative autoregulation of these two transcription units and the effect of mutations on gene expression, we propose a model in which the flaN and flbG promoters interact through alternative DNA looping to form structures that are transcriptionally active or inactive. PMID- 8458850 TI - Alcaligenes eutrophus JMP134 "2,4-dichlorophenoxyacetate monooxygenase" is an alpha-ketoglutarate-dependent dioxygenase. AB - The Alcaligenes eutrophus JMP134 tfdA gene, encoding the enzyme responsible for the first step in 2,4-dichlorophenoxyacetic acid (2,4-D) biodegradation, was overexpressed in Escherichia coli, and several enzymatic properties of the partially purified gene product were examined. Although the tfdA-encoded enzyme is typically referred to as 2,4-D monooxygenase, we were unable to observe any reductant-dependent activity. Rather, we demonstrate that this enzyme is a ferrous ion-dependent dioxygenase that uses alpha-ketoglutarate as a cosubstrate. The alpha-ketoglutarate is converted to succinate concomitant with 2,4-D conversion to 2,4-dichlorophenol. By using [1-14C]alpha-ketoglutarate, we established that carbon dioxide is the second product derived from alpha ketoglutarate. Finally, we verified the proposal that glyoxylate is the second product derived from 2,4-D. PMID- 8458852 TI - Purification and characterization of the Saccharomyces cerevisiae BGL2 gene product, a cell wall endo-beta-1,3-glucanase. AB - One of the major proteins of the Saccharomyces cerevisiae cell wall, a beta glucanase (BGL2 gene product), has been isolated and purified to homogeneity under conditions for preserving enzyme activity. The study of enzyme properties of the protein revealed that it is an endo-beta-1,3-glucanase and not an exoglucanase as reported previously (F. Klebl and W. Tanner, J. Bacteriol. 171:6259-6264, 1989). The examination of the glucanase structure showed that the lower apparent molecular mass of the protein (29 kDa) compared with what was calculated from the amino acid sequence of the enzyme (33.5 kDa) is due to anomalous migration in sodium dodecyl sulfate gels and not to posttranslational processing of the polypeptide chain. Of two potential N glycosylation sites at Asn-202 and Asn-284, only the latter site is glycosylated. The overproduction of the beta-glucanase from the high-copy-number plasmid brought about a significant decrease in the growth rate of transformed yeast cells. PMID- 8458851 TI - Cloning and sequencing of the gene for a lactococcal endopeptidase, an enzyme with sequence similarity to mammalian enkephalinase. AB - The gene specifying an endopeptidase of Lactococcus lactis, named pepO, was cloned from a genomic library of L. lactis subsp. cremoris P8-2-47 in lambda EMBL3 and was subsequently sequenced. pepO is probably the last gene of an operon encoding the binding-protein-dependent oligopeptide transport system of L. lactis. The inferred amino acid sequence of PepO showed that the lactococcal endopeptidase has a marked similarity to the mammalian neutral endopeptidase EC 3.4.24.11 (enkephalinase), whereas no obvious sequence similarity with any bacterial enzyme was found. By means of gene disruption, a pepO-negative mutant was constructed. Growth and acid production of the mutant strain in milk were not affected, indicating that the endopeptidase is not essential for growth of L. lactis in milk. PMID- 8458853 TI - The nac (nitrogen assimilation control) gene from Klebsiella aerogenes. AB - The Klebsiella aerogenes nac gene, whose product is necessary for nitrogen regulation of a number of operons, was identified and its DNA sequence determined. The nac sequence predicted a protein a 305 amino acids with a strong similarity to members of the LysR family of regulatory proteins, especially OxyR from Escherichia coli. Analysis of proteins expressed in minicells showed that nac is a single-gene operon whose product has an apparent molecular weight of about 32 kDa as measured in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Immediately downstream from nac is a two-gene operon, the first gene of which encodes another member of the LysR family. Upstream from nac is a tRNAAsn gene transcribed divergently from nac. About 60 bp upstream from the nac open reading frame lies a sequence nearly identical to the consensus for sigma 54 dependent promoters, with the conserved GG and GC nucleotides at -26 and -14 relative to the start of transcription. About 130 bp farther upstream (at -153 relative to the start of transcription) is a sequence nearly identical to the transcriptional activator NTRC-responsive enhancer consensus. Another weaker NTRC binding site is located adjacent to this site (at -133 relative to the start of transcription). Thus, we propose that nac is transcribed by RNA polymerase carrying sigma 54 in response to the nitrogen regulatory (NTR) system. A transposon located between the promoter and the nac ORF prevented NTR-mediated expression of nac, supporting this identification of the promoter sequence. The insertion of over 5 kb of transposon DNA between the enhancer and its target promoter had only a weak effect on enhancer-mediated regulation, suggesting that enhancers may be able to act at a considerable distance on the bacterial chromosome. PMID- 8458855 TI - Evidence for plasmid-encoded virulence factors in the phytopathogenic bacterium Clavibacter michiganensis subsp. michiganensis NCPPB382. AB - The tomato pathogen Clavibacter michiganensis subsp. michiganensis NCPPB382, which causes bacterial wilt, harbors two plasmids pCM1 (27.5 kb) and pCM2 (72 kb). After curing of the plasmids, bacterial derivatives were still proficient in the ability to colonize the host plant and in the production of exopolysaccharides but exhibited a reduced virulence. When one of the two plasmids is lost, there is a significant delay in the development of wilting symptoms after infection and a plasmid-free derivative is not able to induce disease symptoms. By cloning of restriction fragments of both plasmids in the plasmid-free strain CMM100, two DNA fragments which restored the virulent phenotype were identified. Further analysis suggested that a fragment of plasmid pCM1 encodes an endocellulase which is involved in the expression of the pathogenic phenotype. PMID- 8458854 TI - The product of the Klebsiella aerogenes nac (nitrogen assimilation control) gene is sufficient for activation of the hut operons and repression of the gdh operon. AB - In Klebsiella aerogenes, the formation of a large number of enzymes responds to the quality and quantity of the nitrogen source provided in the growth medium, and this regulation requires the action of the nitrogen regulatory (NTR) system in every case known. Nitrogen regulation of several operons requires not only the NTR system, but also NAC, the product of the nac gene, raising the question of whether the role of NAC is to activate operons directly or by modifying the specificity of the NTR system. We isolated an insertion of the transposon Tn5tac1 which puts nac gene expression under the control of the IPTG-inducible tac promoter rather than the nitrogen-responsive nac promoter. When IPTG was present, cells carrying the tac-nac fusion activated NAC-dependent operons and repressed NAC-repressible operons independent of the nitrogen supply and even in the absence of an active NTR system. Thus, NAC is sufficient to regulate operons like hut (encoding histidase) and gdh (encoding glutamate dehydrogenase), confirming the model that the NTR system activates nac expression and NAC activates hut and represses gdh. Activation of urease formation occurred at a lower level of NAC than that required for glutamate dehydrogenase repression, and activation of histidase formation required still more NAC. PMID- 8458856 TI - The putative sigma factor KatF is regulated posttranscriptionally during carbon starvation. AB - Transcriptional and translational 'lacZ reporter fusions were constructed to the katF gene, which encodes a putative sigma factor centrally involved in starvation mediated general resistance in Escherichia coli. Transcription of katF was found to increase ca. twofold after carbon starvation in minimal medium. The protein fusion containing the longest fragment of katF induced ca. eightfold under the same conditions, whereas fusions to shorter segments showed only a twofold increase in expression. The protein fusion was expressed at higher levels in a strain containing a katF::Tn10 mutation, indicating katF autoregulation. The posttranscriptional regulation of katF by starvation did not require a component of the spent minimal medium. katF was also posttranscriptionally regulated during entry into late log phase in complex medium. This induction was coincident with an increase in katE transcription, suggesting that the cellular concentration of KatF directly followed the induction of the katF protein fusion. PMID- 8458857 TI - KatF (sigma S) synthesis in Escherichia coli is subject to posttranscriptional regulation. AB - A transcriptional fusion of katF to the lacZ gene was expressed at increasingly higher levels throughout the exponential phase, but a translational fusion was expressed at low levels during exponential-phase growth and was induced 160-fold during the transition to stationary phase, implicating a posttranscriptional mechanism in the regulation of KatF synthesis. Mutational analyses suggested that the initiation codon of katF is the second ATG in the previously identified open reading frame. PMID- 8458858 TI - The Escherichia coli visA gene encodes ferrochelatase, the final enzyme of the heme biosynthetic pathway. AB - An Escherichia coli mutant with a disrupted visA gene was defective in ferrochelatase activity but expressed wild-type levels of protoporphyrinogen oxidase activity. The visA coding region was placed under the transcriptional control of T7 RNA polymerase in an E. coli expression system, and the product was expressed as a 38-kDa protein. The overexpressed protein was purified to near homogeneity and was found to contain ferrochelatase activity. The data show that the visA gene encodes ferrochelatase, and we propose that it be renamed hemH to reflect that conclusion. PMID- 8458859 TI - Heat shock-induced axenic growth of Bdellovibrio bacteriovorus. AB - The bdellovibrios are obligately predatory bacteria that attack other gram negative bacteria. They grow only in the periplasmic space of prey unless they mutate to forms that can grow axenically. A culture medium that promoted enhanced growth of prey-independent bdellovibrios was developed. The ability of this medium to support the growth of prey-dependent bdellovibrios was tested under transcription-altering conditions. This approach tested the hypothesis that the inability to grow prey-dependent bdellovibrios in artificial media was rooted in both nutritional and transcriptional signal deficiencies. It was assumed that nutritional deficiencies had been resolved and that empirically applied artificial signals may evoke the expression of genes required for axenic growth of bdellovibrios. Prey-dependent bdellovibrios could be grown in PPYE medium (0.1% proteose peptone 3 and 0.03% Bacto yeast extract adjusted to pH 7.0 and supplemented with 3 mM MgCl2 and 2 mM CaCl2 after autoclaving) after heat shock, and subsequent rounds of growth occurred after additional heat shocks. Heat shock may have generated or simulated signals normally derived from prey. PMID- 8458860 TI - Characterization of an Escherichia coli aromatic hydroxylase with a broad substrate range. AB - The hpaB gene encoding an aromatic hydroxylase of Escherichia coli ATCC 11105, a penicillin G acylase-producing strain, has been cloned and expressed in E. coli K 12. This gene was located near the pacA gene coding for penicillin G acylase. The hydroxylase has a molecular mass of 59,000 Da, uses NADH as a cosubstrate, and was tentatively classified as a 4-hydroxyphenylacetic acid hydroxylase, albeit it exhibited a rather broad substrate specificity acting on different monohydric and dihydric phenols. E. coli W, C, and B as well as Klebsiella pneumoniae M5a1 and Kluyvera citrophila ATCC 21285 (a penicillin G acylase-producing strain) but not E. coli K-12 contained sequences homologous to hpaB. Our results support the hypothesis that hpaB is a component of the 4-hydroxyphenylacetic acid degradative pathway of E. coli W. PMID- 8458861 TI - Nup155 is a novel nuclear pore complex protein that contains neither repetitive sequence motifs nor reacts with WGA. AB - We have molecularly cloned and sequenced a rat liver nuclear pore complex (NPC) protein of calculated molecular mass of 155 kD. Consistent with recently proposed nomenclature this protein is termed nucleoporin 155, or nup155. Unlike other nups that have so far been molecularly cloned and sequenced, nup155 does not contain repetitive sequence domains. It does not show similarity to the sequences of other proteins, including any nups, so far compiled in the data bases. Like other vertebrate nups which have been characterized nup155 possesses abundant (46 in total) consensus sites for various kinases. By immunoelectron microscopy, nup155 is associated with both the nucleoplasmic and the cytoplasmic aspect of the NPC and is therefore possibly a component of the symmetrically arranged NPC substructures. In mitotic cells, nup155 assumes a diffuse cytoplasmic distribution. Nup155 is among the integral of 30 proteins that were extracted from rat liver nuclear envelopes by 2.0 M urea/1.0 mM EDTA, separated from WGA reactive proteins by WGA-Sepharose and further subfractionated by SDS hydroxylapatite. These proteins are potential candidates for being nups. PMID- 8458862 TI - Regulation of the cell cycle by the cdk2 protein kinase in cultured human fibroblasts. AB - In mammalian cells inhibition of the cdc2 function results in arrest in the G2 phase of the cell cycle. Several cdc2-related gene products have been identified recently and it has been hypothesized that they control earlier cell cycle events. Here we have studied the relationship between activation of one of these cdc2 homologs, the cdk2 protein kinase, and the progression through the cell cycle in cultured human fibroblasts. We found that cdk2 was activated and specifically localized to the nucleus during S phase and G2. Microinjection of affinity-purified anti-cdk2 antibodies but not of affinity-purified anti-cdc2 antibodies, during G1, inhibited entry into S phase. The specificity of these effects was demonstrated by the fact that a plasmid-driven cdk2 overexpression counteracted the inhibition. These results demonstrate that the cdk2 protein kinase is involved in the activation of DNA synthesis. PMID- 8458863 TI - Expression of mutant ELH prohormones in AtT-20 cells: the relationship between prohormone processing and sorting. AB - Posttranslational processing of many proteins is essential to the synthesis of fully functional molecules. The ELH (egg-laying hormone) prohormone is cleaved by endoproteases in a specific order at a variety of basic residue processing sites to produce mature peptides. The prohormone is first cleaved at a unique tetrabasic site liberating two intermediates (amino and carboxy) which are sorted to different classes of dense core vesicles in the bag cell neurons of Aplysia. When expressed in AtT-20 cells, the ELH prohormone is also first cleaved at the tetrabasic site. The amino-terminal intermediate is then sorted to the constitutive pathway, and a portion of the carboxy-terminal intermediate is sorted to the regulated pathway. Here, we use mutant constructs of the ELH prohormone expressed in AtT-20 cells to examine the relationship between prohormone processing and consequent sorting. Prohormone which has a dibasic site in place of the tetrabasic site is processed and sorted similarly to wild type. Furthermore, mutant prohormone which lacks the tetrabasic site is processed at an alternative site comprising three basic residues. In these mutant prohormones, mature ELH is still produced and stored in dense core vesicles while amino terminal products are constitutively secreted. However, deletion of the tetrabasic and tribasic sites results in the rerouting of the amino-terminal intermediate products from the constitutive pathway to the regulated secretory pathway. Thus, in the ELH prohormone, the location of the proteolytic processing events within the secretory pathway and the order of cleavages regulate the sorting of peptide products. PMID- 8458864 TI - Interference with endogenous ras function inhibits cellular responses to wounding. AB - Wounding of tissue induces cellular responses that ultimately result in wound repair. Studies in tissue culture model systems indicate that these responses include induction of AP-1 regulated genes, cell migration and mitogenesis which are also characteristic of cellular responses to growth factors. Investigations have identified cellular ras proteins as critical components of growth factor stimulated signal transduction pathways, however their role in the wounding response is less clear. Investigation of the potential involvement of c-Ras in this process utilized quiescent living bovine corneal endothelium cells (BCE) which were microinjected with ras dominant interfering mutant protein (N17) and subsequently stimulated by mechanical wounding. Analysis of these cells demonstrated that microinjection of dominant-interfering ras protein, but not control proteins, inhibited the wounding response as evidenced by diminished Fos expression, lack of cell migration and a block in DNA synthesis. PMID- 8458865 TI - Ankyrin-binding proteins related to nervous system cell adhesion molecules: candidates to provide transmembrane and intercellular connections in adult brain. AB - A major class of ankyrin-binding glycoproteins have been identified in adult rat brain of 186, 155, and 140 kD that are alternatively spliced products of the same pre-mRNA. Characterization of cDNAs demonstrated that ankyrin-binding glycoproteins (ABGPs) share 72% amino acid sequence identity with chicken neurofascin, a membrane-spanning neural cell adhesion molecule in the Ig super family expressed in embryonic brain. ABGP polypeptides have the following features consistent with a role as ankyrin-binding proteins in vitro and in vivo: (a) ABGPs and ankyrin associate as pure proteins in a 1:1 molar stoichiometry; (b) the ankyrin-binding site is located in the COOH-terminal 21 kD of ABGP186 which contains the predicted cytoplasmic domain; (c) ABGP186 is expressed at approximately the same levels as ankyrin (15 pmoles/milligram of membrane protein); and (d) ABGP polypeptides are co-expressed with the adult form of ankyrinB late in postnatal development and are colocalized with ankyrinB by immunofluorescence. Similarity in amino acid sequence and conservation of sites of alternative splicing indicate that genes encoding ABGPs and neurofascin share a common ancestor. However, the major differences in developmental expression reported for neurofascin in embryos versus the late postnatal expression of ABGPs suggest that ABGPs and neurofascin represent products of gene duplication events that have subsequently evolved in parallel with distinct roles. The predicted cytoplasmic domains of rat ABGPs and chicken neurofascin are nearly identical to each other and closely related to a group of nervous system cell adhesion molecules with variable extracellular domains, which includes L1, Nr-CAM, and Ng CAM of vertebrates, and neuroglian of Drosophila. The ankyrin-binding site of rat ABGPs is localized to the C-terminal 200 residues which encompass the cytoplasmic domain, suggesting the hypothesis that ability to associate with ankyrin may be a shared feature of neurofascin and related nervous system cell adhesion molecules. PMID- 8458866 TI - Astrocytes and neurosteroids: metabolism of pregnenolone and dehydroepiandrosterone. Regulation by cell density. AB - The rat central nervous system (CNS) has previously been shown to synthesize pregnenolone (PREG) and convert it to progesterone (PROG) and 7 alpha-hydroxy PREG (7 alpha-OH PREG). Astrocytes, which participate to the regulation of the CNS function, might be involved in the metabolism of neurosteroids. Purified type 1 astrocytes were obtained from fetal rat forebrain with the use of selective culture conditions and were identified by immunostaining with specific antibodies (GFAP+, A2B5-). They were plated at low, intermediate, or high densities (2.5-5 x 10(5), 1-2 x 10(6), or 4-8 x 10(6) cells/dish, respectively) and maintained for 21 d. They were then incubated with 14C-PREG and 14C-DHEA for 24 h and the steroids extracted from cells and media were analyzed. Most radioactive derivatives were released into incubation media. Two metabolic pathways were mainly observed. PREG and DHEA were oxidized to PROG and androstenedione (ADIONE), respectively, [3 beta-hydroxysteroid-dehydrogenase, delta 5-->4 3 ketosteroid-isomerase (3 beta-HSD) activity], and converted to 7 alpha-OH PREG and 7 alpha-OH DHEA, respectively (7 alpha-hydroxylase activity). After low density plating, the formation of PROG and ADIONE was approximately 10% of incubated radioactivity, tenfold larger than that of 7 alpha-hydroxylated metabolites. In contrast, after high density plating, low levels of PROG and ADIONE were formed, whereas the conversion to either 7 alpha-OH PREG or 7 alpha OH DHEA was > or = 50%. The results expressed per cell indicated that the 3 beta HSD activity was almost completely inhibited at high cell density, in contrast to the 7 alpha-hydroxylation which was maintained or increased. The pattern of steroid metabolism was related to cell density at the time of measurement and not to an early commitment of cells: when primary cultures were plated at high density (8 x 10(6) cells/dish), then subcultured after several dilutions (3-, 9-, or 27-fold), the 3 beta-HSD activity was recovered only at low density. Furthermore, when 5 x 10(5) cells were centrifuged and the resulting clusters were plated, 3 beta-HSD activity was decreased, whereas steroid 7 alpha hydroxylation was enhanced. This implies that cell density per se, but neither cell number nor a diffusible factor(s) is involved in the regulation of steroid metabolism. We conclude that astrocytes in culture metabolize PREG and DHEA, and that the metabolic conversions and, therefore, the related enzymatic activities depend on cell-to-cell contacts.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8458867 TI - Affinity modulation of integrin alpha 5 beta 1: regulation of the functional response by soluble fibronectin. AB - We report that a beta 1 integrin (alpha 5 beta 1) can exist in different affinity states for its soluble ligand, fibronectin. The alpha 5 beta 1 expressed by the erythroleukemic cell line K562 binds soluble fibronectin with low affinity (Kd > 1 microM), but is induced to bind it with 20-fold higher affinity (Kd-54 nM) in the presence of the anti-beta 1 mAb 8A2. This activation seems to be due to direct antibody-induced change in the receptor that does not require intracellular signaling, and is a plausible basis for the 8A2-induced enhancement of beta 1-dependent adhesion to fibronectin and other immobilized ligands (Kovach, N. L., T. M. Carlos, E. Yee, and J. M. Harlan. 1992. J. Cell Biol. 116: 499-509). Fab fragments of 8A2 bind with higher affinity to alpha 5 beta 1 receptor that is occupied by the GRG-DSP peptide ligand suggesting that the antibody functions by stabilizing a high affinity (occupied) conformer of the receptor. A functional consequence of the affinity modulation is that soluble fibronectin (at physiological concentrations) occupies the high affinity receptors, and so becomes an effective inhibitor of adhesion to immobilized fibronectin. In contrast, the majority of low affinity receptors remain unoccupied and are still to mediate cellular adhesion. PMID- 8458868 TI - Parallel regulation of procollagen I and colligin, a collagen-binding protein and a member of the serine protease inhibitor family. AB - A potential regulatory linkage between the biosynthesis of colligin, a collagen binding protein of the ER, and procollagen I was examined under a variety of experimental conditions. Cell lines which did not produce a significant amount of procollagen I mRNA also lacked the capacity to produce colligin mRNA. Anchorage dependent cell lines like L6 myoblasts and normal rat kidney fibroblasts produced both colligin and procollagen I mRNA, but the level of both was concurrently reduced considerably in their ras-transformed counterparts. Similarly, during the differentiation of L6 myoblasts, levels of both colligin and procollagen declined together. Treatment of myoblasts by dexamethasone or EGF led to a decrease in the steady-state levels of procollagen I mRNA, and this was, again, accompanied by a decrease in colligin mRNA synthesis. On the other hand, when the rate of procollagen I synthesis was stimulated by treatment of myoblasts with TGF beta, it led to the concurrent augmentation of both the mRNA and protein levels of colligin. A linkage between the regulation of synthesis of procollagen I and colligin thus seems to exist. The only exception to this generalization is provided by the heat induction behavior of the two proteins. Treatment of myoblasts for a very short period leads to an increase in the synthesis of both the mRNA and protein levels of colligin. This, however, is not accompanied by a change in the mRNA levels of procollagen I. These studies establish that colligin and procollagen are generally tightly co-regulated except after heat shock, suggesting an important functional linkage. PMID- 8458869 TI - Emilin, a component of elastic fibers preferentially located at the elastin microfibrils interface. AB - The fine distribution of the extracellular matrix glycoprotein emilin (previously known as glycoprotein gp115) (Bressan, G. M., I. Castellani, A. Colombatti, and D. Volpin. 1983. J. Biol. Chem. 258: 13262-13267) has been studied at the ultrastructural level with specific antibodies. In newborn chick aorta the protein was exclusively found within elastic fibers. In both post- and pre embedding immunolabeling emilin was mainly associated with regions where elastin and microfibrils are in close contact, such as the periphery of the fibers. This localization of emilin in aorta has been confirmed by quantitative evaluation of the distribution of gold particles within elastic fibers. In other tissues, besides being associated with typical elastic fibers, staining for emilin was found in structures lacking amorphous elastin, but where the presence of tropoelastin has been demonstrated by immunoelectron microscopy. This was particularly evident in the oxitalan fibers of the corneal stroma, in the Descemet's membrane, and in the ciliary zonule. Analysis of embryonic aorta revealed the presence of emilin at early stages of elastogenesis, before the appearance of amorphous elastin. Immunofluorescence studies have shown that emilin produced by chick embryo aorta cells in culture is strictly associated with elastin and that the process of elastin deposition is severely altered by the presence of antiemilin antibodies in the culture medium. The name of the protein was derived from its localization at sites where elastin and microfibrils are in proximity (emilin, elastin microfibril interface located protein). PMID- 8458870 TI - COOH-terminal signals mediate the trafficking of a peptide processing enzyme in endocrine cells. AB - Peptidylglycine alpha-amidating monooxygenase (PAM) catalyzes the COOH-terminal amidation of bioactive peptides through a two step reaction catalyzed by separate enzymes contained within the PAM precursor. To characterize the trafficking of integral membrane PAM proteins in neuroendocrine cells, we have generated stable AtT-20 cell lines expressing full length and COOH-terminally truncated integral membrane PAM proteins. Full length integral membrane PAM was present on the cell surface in low but detectable amounts and PAM proteins which reached the cell surface were rapidly internalized but not immediately degraded in lysosomes. Internalized PAM complexed with PAM antibody was found in a subcellular compartment which overlapped with internalized transferrin and with structures binding WGA. Thus the punctate juxtanuclear staining of full length PAM represents PAM in endosomes. Endoproteolytic processing of full length PAM-1 and PAM-2 resulted in the secretion of soluble PAM proteins; the secretion of these soluble PAM proteins was stimulus dependent. Although some of the truncated PAM protein was also processed and stored in AtT-20 cells, much of the expressed protein was redistributed to the plasma membrane. Soluble proteins not observed in large amounts in cells expressing full length PAM were released from the surface of cells expressing truncated PAM and little internalization of truncated integral membrane PAM was observed. Thus, the COOH-terminal domain of PAM contains information important for its trafficking within the regulated secretory pathway as well as information necessary for its retrieval from the cell surface. PMID- 8458871 TI - Functional activation of plasma membrane anion exchangers occurs in a pre-Golgi compartment. AB - Folding and oligomerization of most plasma membrane glycoproteins, including those involved in ion transport, occur in the ER and are frequently required for their exit from this organelle. It is currently unknown, however, where or when in the biosynthetic pathway these proteins become functionally active. AE1 and AE2 are tissue-specific, plasma membrane anion transport proteins. Transient expression of AE2 in a eukaryotic cell line leads to an increase in stilbene inhibitable whole cell 35SO4(2-)-efflux consistent with its function as a plasma membrane anion exchanger. No such increased transport activity was observed in AE1 transfectants, despite the fact that the two proteins were synthesized in roughly equal portions. In contrast, both AE1 and AE2 expression resulted in significant increase in Cl-/SO4(2-)-exchange in crude microsomes demonstrating that both AE1 and AE2 cDNAs encode functional proteins. Immunofluorescence staining and pulse-chase labeling experiments revealed that while 60% of AE2 is processed to the cell surface of transfectants, AE1 is restricted to an intracellular compartment and never acquires mature oligosaccharides. Crude microsomes from transfected cells were fractionated into plasma membrane and ER derived vesicles by con A affinity chromatography. All of the AE1 and approximately half of the cellular AE2 was eluted with the ER vesicles, confirming their intracellular localization. Anion transport measurements on these fractions confirmed that the ER-restricted anion exchangers were functional. We conclude that AE1 and AE2 acquire the ability to mediate anion exchange at an early stage of their biosynthesis, before their exit from the ER. PMID- 8458872 TI - Beta-COP localizes mainly to the cis-Golgi side in exocrine pancreas. AB - We examined the distribution of the non-clathrin-coated vesicle-associated coat protein beta-COP in rat exocrine pancreatic cells by immunogold cytochemistry. Labeling for beta-COP was found in the Golgi region (48%) where it was associated with vesicles and buds of approximately 50 nm, showing a characteristic approximately 10-nm-thick coat. The other half of the label was present in the cytoplasm, not associated with visible coats or membranes, with a minor fraction present on small clusters of tubules and vesicles. Clathrin-coated vesicles were typically located at the trans-side of the Golgi complex, and showed a thicker coat of approximately 18 nm. Of the total beta-COP labeling over the Golgi region, 68% occurred on the cis-side, 6% on the cisternae, 17% on the rims of the cisternae, and only 9% on the trans-side. For clathrin these figures were 16, 2, 4, and 78%, respectively. At the cis-Golgi side beta-COP was present in transitional areas (TA), on so-called peripheral elements (PE), consisting of tubules and vesicles located between the cup-shaped transitional elements (TE) of the RER and the cis-most Golgi cisternae. Label for Sec23p was also present in TA but was located closer to the TE, while beta-COP labeled PE were located near the cis-Golgi cisternae. Upon energy depletion, Golgi associated beta-COP was almost exclusively (86%) in spherical aggregates of 200-500 nm in diameter, whereas the cis-side (6%), the cisternae (1%), the rims (4%) and trans-side (3%) of the Golgi complex, were barely labeled; 50% of the total label remained in the cytoplasm. The aggregates were predominantly located at the cis-side of the Golgi stack, next to, but distinct from the Sec23p positive TA, that were devoid of beta-COP and had only a few recognizable vesicles left. Incubation with aluminum fluoride resulted in fragmentation of the Golgi complex into large clusters of beta-COP positive vesicles, while 50% of the label remained in the cytoplasm, as in control cells. After 10 min of Brefeldin A treatment 91% of beta-COP was cytoplasmic and only 7% associated with membranes of the Golgi complex. The total label for beta-COP over exocrine cells remained unchanged during the incubation with either of the drugs, indicating that the drugs induce reallocation of beta COP. Our data suggest that beta-COP plays a role in membrane transport at the cis side of the Golgi complex. PMID- 8458873 TI - Clathrin and HA2 adaptors: effects of potassium depletion, hypertonic medium, and cytosol acidification. AB - The effects of methods known to perturb endocytosis from clathrin-coated pits on the localization of clathrin and HA2 adaptors in HEp-2 carcinoma cells have been studied by immunofluorescence and ultrastructural immunogold microscopy, using internalization of transferrin as a functional assay. Potassium depletion, as well as incubation in hypertonic medium, remove membrane-associated clathrin lattices: flat clathrin lattices and coated pits from the plasma membrane, and clathrin-coated vesicles from the cytoplasm, as well as those budding from the TGN. In contrast, immunofluorescence microscopy using antibodies specific for the alpha- and beta-adaptins, respectively, and immunogold labeling of cryosections with anti-alpha-adaptin antibodies shows that under these conditions HA2 adaptors are aggregated at the plasma membrane to the same extent as in control cells. After reconstitution with isotonic K(+)-containing medium, adaptor aggregates and clathrin lattices colocalize at the plasma membrane as normally and internalization of transferrin resumes. Acidification of the cytosol affects neither clathrin nor HA2 adaptors as studied by immunofluorescence microscopy. However, quantitative ultrastructural observations reveal that acidification of the cytosol results in formation of heterogeneously sized and in average smaller clathrin-coated pits at the plasma membrane and buds on the TGN. Collectively, our observations indicate that the methods to perturb formation of clathrin coated vesicles act by different mechanisms: acidification of the cytosol by affecting clathrin-coated membrane domains in a way that interferes with budding of clathrin-coated vesicles from the plasma membrane as well as from the TGN; potassium depletion and incubation in hypertonic medium by preventing clathrin and adaptors from interacting. Furthermore our observations show that adaptor aggregates can exist at the plasma membrane independent of clathrin lattices and raise the possibility that adaptor aggregates can form nucleation sites for clathrin lattices. PMID- 8458874 TI - Noncoding regions of the gamma-actin gene influence the impact of the gene on myoblast morphology. AB - We have addressed the question of whether two highly conserved noncoding regions of the gamma-actin gene are of functional importance. Human gamma-actin gene constructs deleted for either the entire 3' untranslated region (UTR) and 3' flank or intron III sequences were transfected into mouse myoblasts and the resulting clones were analyzed for cell morphology and actin protein expression. Transfectants carrying the gamma-actin gene deleted for the 3' end (gamma 22) exhibited numerous long pseudopods and increased surface area. In contrast, transfectants expressing the gamma-actin gene deleted for intron III (gamma 156) were rounded with blebs over the cell surface and showed decreased surface area. The relative expression of beta- to gamma-actin protein decreased for both transfectant types. The total actin protein levels remained constant for the gamma 22 cells but decreased for the gamma 156 cells. The results indicate that alterations to transfectant cell morphology can be influenced by the presence or absence of different noncoding regions in the transfected gamma-actin gene. The mechanisms by which noncoding regions of the gamma-actin gene influence the impact of the gene are unknown. Nevertheless, these noncoding regions are isoform specific and highly conserved in evolution. We propose that the functional significance of the different actin isoforms may involve the properties of these noncoding regions in addition to the differences in protein sequence. PMID- 8458875 TI - Imaging calcium dynamics in living plants using semi-synthetic recombinant aequorins. AB - The genetic transformation of the higher plant Nicotiana plumbaginifolia to express the protein apoaequorin has recently been used as a method to measure cytosolic free calcium ([Ca2+]i) changes within intact living plants (Knight, M. R., A. K. Campbell, S. M. Smith, and A. J. Trewavas. 1991. Nature (Lond.). 352:524-526; Knight, M. R., S. M. Smith, and A. J. Trewavas. 1992. Proc. Natl. Acad. Sci. USA. 89:4967-4971). After treatment with the luminophore coelenterazine the calcium-activated photoprotein aequorin is formed within the cytosol of the cells of the transformed plants. Aequorin emits blue light in a dose-dependent manner upon binding free calcium (Ca2+). Thus the quantification of light emission from coelenterazine-treated transgenic plant cells provides a direct measurement of [Ca2+]i. In this paper, by using a highly sensitive photon counting camera connected to a light microscope, we have for the first time imaged changes in [Ca2+]i in response to cold-shock, touch and wounding in different tissues of transgenic Nicotiana plants. Using this approach we have been able to observe tissue-specific [Ca2+]i responses. We also demonstrate how this method can be tailored by the use of different coelenterazine analogues which endow the resultant aequorin (termed semi-synthetic recombinant aeqorin) with different properties. By using h-coelenterazine, which renders the recombinant aequorin reporter more sensitive to Ca2+, we have been able to image relatively small changes in [Ca2+]i in response to touch and wounding: changes not detectable when standard coelenterazine is used. Reconstitution of recombinant aequorin with another coelenterazine analogue (e-coelenterazine) produces a semi-synthetic recombinant aequorin with a bimodal spectrum of luminescence emission. The ratio of luminescence at two wavelengths (421 and 477 nm) provides a simpler method for quantification of [Ca2+]i in vivo than was previously available. This approach has the benefit that no information is needed on the amount of expression, reconstitution or consumption of aequorin which is normally required for calibration with aequorin. PMID- 8458876 TI - Mediation of growth factor induced DNA synthesis and calcium mobilization by Gq and Gi2. AB - A newly identified subclass of the heterotrimeric GTP binding regulatory protein family, Gq, has been found to be expressed in a diverse range of cell types. We investigated the potential role of this protein in growth factor signal transduction pathways and its potential relationship to the function of other G alpha subclasses. Recent biochemical studies have suggested that Gq regulates the beta 1 isozyme of phospholipase C (PLC beta 1), an effector for some growth factors. By microinjection of inhibitory antibodies specific to distinct G alpha subunits into living cells, we have determined that G alpha q transduces bradykinin- and thrombin-stimulated intracellular calcium transients which are likely to be mediated by PLC beta 1. Moreover, we found that G alpha q function is required for the mitogenic action of both of these growth factors. These results indicate that both thrombin and bradykinin utilize Gq to couple to increases in intracellular calcium, and that Gq is a necessary component of the mitogenic action of these factors. While microinjection of antibodies against G alpha i2 did not abolish calcium transients stimulated by either of these factors, such microinjection prevented DNA synthesis in response to thrombin but not to bradykinin. These data suggest that thrombin-induced mitogenesis requires both Gq and Gi2, whereas bradykinin needs only the former. Thus, different growth factors operating upon the same cell type use overlapping yet distinct sets of G alpha subtypes in mitogenic signal transduction pathways. The direct identification of the coupling of both a pertussis toxin sensitive and insensitive G protein subtype in the mitogenic pathways utilized by thrombin offers an in vivo biochemical clarification of previous results obtained by pharmacologic studies. PMID- 8458877 TI - Serum concentration and cardiovascular effects of salbutamol after oral and rectal administration in healthy volunteers. AB - In order to evaluate rectal administration of salbutamol (SB), five healthy volunteers were dosed orally and rectally with racemic SB (0.1 mg/kg) solution. Compared with the oral SB, the rectal SB gave significantly higher serum SB concentration immediately after dosing but slightly lower levels in the elimination phase. The Cmax following rectal administration was 17.9 ng/ml (17.0 ng/ml for oral administration), the tmax 0.67 h (1.5 h for oral administration) and the AUC 98.2 ng/ml/h (100 ng/ml/h for oral administration). Heart rate also rose more rapidly to a maximum of 70% above baseline values after rectal dosing. The rate continued to be twice larger than after oral dosing for up to 5 h. The concentration versus response curves indicated that rectal SB was more effective than oral SB at increasing heart rate at the same SB concentration in serum. A plausible explanation for this phenomenon might be a difference in the stereo selective first-pass metabolism of the two enantiomers. Therefore, the rectal dose of SB administered as a suppository for prophylactic treatment of asthma should be lower than that used orally. PMID- 8458878 TI - Analysis and bioequivalency study on two tablet formulations of co-trimoxazole. AB - This paper describes an analytical procedure for simultaneous quantification of trimethoprim (TMP) and sulphamethoxazole (SMZ) in serum. Serum samples were rendered alkaline with glycine-sodium hydroxide buffer (pH 9.1) and extracted with ethyl acetate. The reconstituted sample was analysed using reversed-phase C 18 column high-performance chromatography. The mobile phase consisted of 75% triethyl ammonium acetate buffer, 20% methanol and 5% acetonitrile. The analytes were monitored at 289 nm and tetroxoprim was used as an internal standard. The maximum values for intra-day coefficients of variation (CV) for TMP-and SMZ were 5.7 and 2.1%, respectively. Interday CV values were 6.4 and 2.2%, respectively. The method was used to compare the bioavailability of two tablet formulations in terms of their pharmacokinetic parameters following oral administration of the tablets to 18 volunteers. PMID- 8458879 TI - Arterial and venous blood samplings in pharmacokinetic studies: vancomycin in rabbits. AB - The pharmacokinetics of vancomycin were evaluated simultaneously using both arterial and venous plasma data in five rabbits after a rapid bolus intravenous (i.v.) dosing. Initial arterial to venous concentration ratios at 5 s after i.v. injection were the highest, with values of 27.1, 36.2, 36.6, 43.7 and 29.7 for rabbits 1-5, respectively. This could be the result of diffusion of vancomycin from the arterial plasma into the extravascular tissues. Both curves decayed in parallel at the terminal phase with the venous levels higher than the arterial levels by 23, 37, 34, 13 and 14% for rabbits 1-5, respectively. This difference could be the result of continuous release of vancomycin from the extravascular tissues to the venous blood. Detailed analysis showed differences in various pharmacokinetic parameters based on arterial and venous data. For example, values for venous Vc were 9.2, 11, 1.9, 7.2 and 8.8 times greater than the arterial values for rabbits 1-5, respectively. The values for both venous Vss and MRT were higher than those of the arterial values in all five rabbits studied. This could be due to more extensive distribution of vancomycin in the extravascular tissues. A plot of 1/Q (urine flow rate) versus 1/ClR of vancomycin yielded a straight line in rabbits 6-10, indicating that the renal clearance of vancomycin in rabbits is dependent upon urine flow. PMID- 8458880 TI - Physicochemical properties of parenteral fat emulsions containing 20% triglyceride; Intralipid and Ivelip. AB - The paper describes an in-depth study of the parenteral fat emulsions, Intralipid 20% and Ivelip 20%. A large number of emulsion samples from separate containers and batches was sampled. The parameters measured were droplet size (both by photon correlation and laser diffraction), pH and zeta potential. These parameters were re-measured after the emulsions were subjected to a number of accelerated stability tests (freeze-thaw cycling, autoclaving and shaking). The results demonstrate that although the Intralipid is stable, it can show some variability between separate batches. The stability of Ivelip is high, and the variability between separate batches is extremely low. PMID- 8458881 TI - Decontamination methods for cytotoxic drugs. 1. Use of a bioluminescent technique to monitor the inactivation of methotrexate with chlorine-based agents. AB - A new microbial bioluminescence assay has been used to monitor the loss of mutagenicity on inactivation of methotrexate by active chlorine-based agents. The drug was degraded to products that were non-active in this mutagen detection system, in agreement with previously described work. Presept granules appear to be a suitable alternative to sodium hypochlorite for inactivating solutions and surface spills of methotrexate. The bioluminescence assay appears to have potential for monitoring clean-up and decontamination procedures in areas where cytotoxic agents are used. PMID- 8458882 TI - Pethidine pharmacokinetics in a heroin addict: a case report. AB - Tolerance to some of the pharmacological actions of the opiates in drug addicts is well known. This report illustrates the effect on the pharmacokinetics of pethidine of heroin addiction compared with a well-matched control population. PMID- 8458883 TI - Tensions in American health care. PMID- 8458884 TI - The current therapy of multiple sclerosis. AB - The mainstay of treatment for multiple sclerosis in the U.K., and worldwide, remains corticosteroid therapy. High-dose pulses of intravenous methylprednisolone is currently the most favoured agent for acute exacerbations or a sudden acceleration in clinical course. Many patients who follow a more insidious decline rely on symptomatic treatments designed to ameliorate the chronic symptoms associated with their condition. Attempts to influence disease progression using a wide range of immune-modulating agents have not to date been of sufficient clinical benefit to justify their routine usage. With increasing understanding of the underlying disease mechanisms future treatments are being more specifically directed toward disease prevention. PMID- 8458885 TI - Can anti-oxidants prevent ischaemic heart disease? AB - Ischaemic heart disease remains a major cause of mortality in developed countries. A number of important risk factors for the development of coronary atherosclerosis have been identified including hypertension, hypercholesterolaemia, insulin resistance and smoking. However, these factors can only partly explain variations in the incidence of ischaemic heart disease either between populations or within populations over time. In addition, population interventions based upon these factors have had little impact in the primary prevention of heart disease. Recent evidence suggests that one of the important mechanisms predisposing to the development of atherosclerosis is oxidation of the cholesterol-rich low-density lipoprotein particle. This modification accelerates its uptake into macrophages, thereby leading to the formation of the cholesterol laden 'foam cell'. In vitro, low-density lipoprotein oxidation can be prevented by naturally occurring anti-oxidants such as vitamin C, vitamin E and beta carotene. This article explores the evidence that these dietary anti-oxidants may influence the rate of progression of coronary atherosclerosis in vivo and discusses the need for formal clinical trials of anti-oxidant therapy. PMID- 8458886 TI - A stability-indicating first-derivative spectrophotometric assay of acetazolamide and its use in dissolution and kinetic studies. AB - A simple, rapid, stability-indicating first-derivative spectrophotometric assay procedure for the determination of the degradation products of acetazolamide is described. The dissolution and kinetics of drug degradation in aqueous buffered solutions were studied using the proposed method. Acetazolamide solution exhibited optimum stability at pH 4. The influences of temperature and sonic energy on the degradation of acetazolamide in 0.01 M NaOH solution were also studied. The results showed first-order reaction kinetics, with a degradation rate constant and degradation half-life of 3.51 x 10(-3) day-1 and 8.23 days, respectively. PMID- 8458887 TI - Presence of N-methyldopamine in parkinsonian and normal human brains. AB - N-Methyldopamine (epinine) has been identified for the first time in parkinsonian and normal human brains by gas chromatography-mass spectrometry. N Methylsalsolinol and N-methylnorsalsolinol, which are analogues of 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine, which produces parkinsonism in humans, may be synthesized from N-methyldopamine by the Pictet-Spengler condensation reaction as an alternative metabolic pathway. PMID- 8458889 TI - Sensitive high-performance liquid chromatographic determination of chlorzoxazone and 6-hydroxychlorzoxazone in plasma. AB - A rapid and sensitive high-performance liquid chromatographic assay was developed for the quantitation of chlorzoxazone and its major metabolite 6 hydroxychlorozoxazone in plasma. These compounds, as well as the internal standard 5-fluorobenzoxazolone, were extracted from plasma (0.5 ml) using C18 solid-phase extraction columns. The extracts were analyzed on a 10-microns Waters C18 muBond-apak column with a mobile phase of acetonitrile-tetrahydrofuran-0.1 M ammonium acetate (22.5:5.5:72). The assay utilized ultraviolet detection (283 nm) which provided sensitivity and specificity sufficient to simultaneously quantify > or = 100 ng/ml chlorozoxazone and 6-hydroxychlorzoxazone in plasma. The mean correlation coefficient of the multi-level standard curves for each compound was 0.996 or greater over a concentration range of 100-3000 ng/ml. The inter-day and intra-day coefficients of variation were < 6%. This method has been used by our laboratory to provide the unattended overnight analysis of chlorozoxazone and 6 hydroxychlorzoxazone in plasma samples obtained from human study subjects. PMID- 8458888 TI - Determination of propranolol, labetalol and clenbuterol in rat brain by high performance liquid chromatography. AB - A rapid and simple HPLC method for the measurement of adrenergic drugs (propranolol, labetalol and clenbuterol) in rat brain is described. This method was applied to establish if these drugs can pass the blood-brain barrier in prenatal or early post-natal life. The chromatography was performed using a C18 column and a phosphate buffer (pH 3)-acetonitrile (65:35, v/v) mixture. After homogenization of the brain tissue in perchloric acid, the supernatant was buffered at pH 9 and extracted with diethyl ether, followed by back-extraction in sulphuric acid. Recoveries of between 80 and 100% were achieved. The method was found to be accurate (100%) and precise (coefficient of variation around 10%). All three drugs were readily detected in the brain of neonatal rats after peripheral administration. In addition, we demonstrated the presence of propranolol in the fetal brain after maternal administration. PMID- 8458890 TI - Determination of urinary 18-hydroxycortisol by isocratic normal-phase high performance liquid chromatography. AB - A method for the determination of urinary 18-hydroxycortisol by high-performance liquid chromatography is described. Urinary samples were first mixed with an internal standard, 18-hydroxyprednisolone. 18-Hydroxycortisol and 18 hydroxyprednisolone, extracted by a Bond Elut column, were dehydrated by 1% (w/v) p-toluenesulphonic acid to the 11,18-epoxides. The epoxides were separated into two distinct peaks on a Resolve Silica column with a mobile phase of chloroform methanol (100:2.5, v/v). The detection wavelength was 248 nm. The urinary 18 hydroxycortisol concentration was calculated from peak-height ratio of 11,18 epoxycortisol to 11,18-epoxyprednisolone. The linearity of the ratio was satisfactory in the range 12.5-300 ng per injection of 11,18-epoxycortisol. A specific increase of urinary 18-hydroxycortisol in patients with primary aldosteronism was demonstrated. PMID- 8458891 TI - Analysis of physiological amino acids using dabsyl derivatization and reversed phase liquid chromatography. AB - A method is described for the measurement of the specific radioactivity of primary amino acids in physiological samples. The amino acids were dabsylated followed by separation using high-performance liquid chromatography. We measured the concentration of amino acids from rat plasma or liver samples. Chromatographic analyses resolved phenylalanine from a mixture of amino acids in plasma within 30 min. An extended chromatographic gradient program completely separated all physiological amino acids within 75 min. This method is as sensitive as any current method of amino acid analysis and offers several advantages including (1) simple pre-column derivatization and (2) stability of derivatized samples. PMID- 8458892 TI - High-performance liquid chromatographic separation of biogenic polyamines using 2 (1-pyrenyl)ethyl chloroformate as a new fluorogenic derivatizing reagent. AB - The application of a new fluorogenic pre-column derivatizing reagent, 2-(1 pyrenyl)ethyl chloroformate (PEOC), is reported for the separation and detection of biogenic polyamines using column liquid chromatography. The development of the method included the optimization of excitation and emission wavelengths, efficient gradient programming, derivatization temperature, time, and pH. Minimum detection limits, linear ranges, reproducibility, and recovery from analyzed samples were determined. The procedure was applied to hydrolyzed serum samples taken from healthy individuals and cancer patients. Separation of PEOC derivatized polyamines from the serum hydrolysis by-products was successful and detection limits were more favorable than those previously reported for 9 fluorenyl-methyl chloroformate-derivatized polyamines. PMID- 8458893 TI - Gas chromatographic-mass spectrometric method for the determination of bifemelane in human plasma at therapeutic doses. AB - A gas chromatographic method with mass-selective detection for the determination of bifemelane in human plasma has been developed. The assay is based on a single hexane extraction and an efficient gas chromatographic separation on a capillary column. The assay has been validated and used to support clinical pharmacokinetic studies. The lowest limit of quantitation was found to be 1 ng/ml and allowed pharmacokinetic evaluation of the drug at doses down to 50 mg. PMID- 8458894 TI - High-performance liquid chromatography of ergometrine and preliminary pharmacokinetics in plasma of men. AB - An isocratic high-performance liquid chromatographic (HPLC) method with fluorescence detection has been developed for the measurement of ergometrine in human plasma. The quantitation limit in plasma was 75 pg/ml. An example of the plasma concentration-time curves obtained after both oral and intravenous administration of ergometrine in one volunteer is shown. This HPLC method makes it possible to describe the pharmacokinetic parameters of oral ergometrine. PMID- 8458895 TI - Identification and quantitation of intact diastereoisomeric benzodiazepine glucuronides in biological samples by high-performance liquid chromatography. AB - A rapid and simple high-performance liquid chromatographic method for the simultaneous detection of intact glucuronides of different benzodiazepines is described. Separation of the diastereomers of the following benzodiazepine glucuronides can be achieved on a reversed-phase column (octadecyl or select B): oxazepam, nordiazepam, temazepam, lorazepam and 3-hydroxyprazepam. If the sample contains both S-lorazepam and R-temazepam glucuronides, or both S-temazepam and nordiazepam glucuronides, further separation on a beta-cyclodextrin column is required. The detection limit ranges between 5 and 10 ng of glucuronides per ml of plasma or urine, respectively. PMID- 8458896 TI - Determination of clozapine and desmethylclozapine in human plasma by high performance liquid chromatography with ultraviolet detection. AB - A method using reversed-phase high-performance liquid chromatography for the simultaneous determination of clozapine and its desmethyl metabolite in human plasma has been established. Clozapine and N-desmethylclozapine were extracted with n-hexane-isoamyl alcohol (98.5:1.5, v/v). Protriptyline served as the internal standard. The limits of detection for clozapine and desmethylclozapine are 2 and 1 ng/ml, respectively. The sensitivity and precision of this method can be utilized for pharmacokinetic studies and therapeutic drug monitoring regimens. PMID- 8458897 TI - Sensitive high-performance liquid chromatographic assay for praziquantel in plasma, urine and liver homogenates. AB - A high-performance liquid chromatographic method for the determination of praziquantel in plasma, urine and rat liver homogenates has been developed. It requires 2 ml of biological fluid, an extraction using Sep-Pak cartridges, a 0.05 M phosphate buffer solution (pH 5.0) for equilibrating and washing and ethyl acetate-diisopropyl ether for drug elution. The analysis was performed on an Ultrasphere ODS C18 column with a mobile phase of acetonitrile-water with ultraviolet detection at 217 nm. The results showed that the assay is sensitive (31.2 ng/ml), linear between 0.125 and 4.0 micrograms/ml, precise (coefficient of variation = 10%) and selective with other drugs currently administered with praziquantel. PMID- 8458898 TI - Simultaneous determination of a new inhibitor of acyl CoA:cholesterol acyltransferase, YM17E, and five metabolites using high-performance liquid chromatography with electrochemical detection. AB - We describe a reversed-phase high-performance liquid chromatographic method for the determination in plasma of YM17E (I), an inhibitor of acyl CoA:cholesterol acyltransferase, and its five metabolites using electrochemical detection. This method enables simultaneous quantification of I and five active metabolites. The plasma sample is extracted by a one-step solid-phase extraction using a SepPak C18 cartridge, with high recovery and reproducibility of the analytes. The method is sensitive and the limits of determination are 0.5 ng/ml for I and 1 ng/ml for metabolites M1, M2-a, M2-b, M3 and M4. This method is applicable to rat, dog and human plasma, and is useful for pharmacokinetic studies. PMID- 8458899 TI - High-performance liquid chromatographic measurement of leucine and alpha ketoisocaproate in whole blood: application to fetal protein metabolism. AB - Evaluation of fetal protein metabolism requires measurement of a number of variables including umbilical blood flow, CO2 radioactivity, as well as plasma specific activities, whole blood concentration, and radioactivity of leucine and alpha-ketoisocaproate. This report details methods of analysis for whole blood concentration and radioactivity of leucine and alpha-ketoisocaproate using high performance liquid chromatography that can be done on minimal blood volumes and are sufficiently accurate to detect the small arteriovenous differences important in measurements of fetal metabolism. Using these methods, the important components of fetal protein metabolism such as protein synthesis can be calculated with sufficient accuracy to detect differences as small as 10% provided appropriate experimental designs are used. PMID- 8458900 TI - High-performance liquid chromatographic determination of amino acids in protein hydrolysates and in plasma using automated pre-column derivatization with o phthaldialdehyde/2-mercaptoethanol. AB - A sensitive and reproducible method for the routine determination of amino acids in plasma and in protein hydrolysates based on reversed-phase high-performance liquid chromatography and o-phthaldialdehyde pre-column derivatization is described. The resolution of all amino acids was found to be good. The total time for analysis, including separation and reconditioning, ranged from 38 min for protein hydrolysates to 62 min for 29 physiological amino acids. The precision of hydrolysate analysis was within a relative standard deviation of 0.8-7.3% depending on the use of internal or external standards. The relative standard deviations of peak areas for physiological amino acids (standard) ranged between 1.8 and 5.6%. The relative standard deviations of retention times were less than 0.5% for all amino acids. This method can be used for routine analysis. One single column with 4-microns end-capped C18 material was found to be sufficient for 400-500 successive runs. PMID- 8458901 TI - Automated high-performance liquid chromatographic determination of hydroxylysylpyridinoline and lysylpyridinoline in urine using a column-switching method. AB - An on-line urine clean-up system was developed for the simultaneous determination of free and total pyridinoline, hydroxylysyl-pyridinoline (HP) and lysylpyridinoline (LP) by high-performance liquid chromatography (HPLC) using a column-switching technique. The method is based on a combination of gel permeation chromatography (GPC) and ion-pair reversed-phase HPLC. In the GPC column, pyridinoline is preseparated from endogenous urinary substances with 0.03 M heptafluorobutyric acid (HFBA) as the mobile phase. After column switching, the eluate fraction containing pyridinoline is further separated by ion-pair chromatography using an octadecylsilica (ODS) column with 0.03 M HFBA acetonitrile (81:19) as the mobile phase. The detection limits were 36 and 44 pmol/ml for free and total HP, respectively, and 44 pmol/ml for both free and total LP at a signal-to-noise ratio of 3. The coefficients of variation for free and total pyridinoline were 1.5 and 3.5%, respectively. The determination of one sample including the clean-up is completed within 25 min. This system is precise and is useful for the determination of pyridinoline in large amounts of urine. The usefulness of pyridinoline as a biomedical marker for bone resorption was also examined. PMID- 8458902 TI - Assay of phenylethanolamine N-methyltransferase activity using high-performance liquid chromatography with ultraviolet absorbance detection. AB - A simple and rapid method for measuring phenylethanolamine N-methyltransferase (PNMT) activity by high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection is described. This assay requires a partially purified PNMT preparation derived from bovine adrenals, with noradrenaline and S-adenosyl-L methionine (SAM) as co-substrates. After incubation, the reaction is stopped by addition of acid and the reaction mixture is analysed directly by HPLC. The enzymatically formed S-adenosyl-L-homocysteine (SAH) is detected at 258 nm and determined. Under optimum conditions, the stability of SAH allowed automation of the HPLC detection. This assay was validated by the determination of the kinetic properties of PNMT. Km values for noradrenaline and SAM defined in this assay (16 and 5.7 microM, respectively) are consistent with previously published values. This assay is simple enough to be used for large series of measurements of PNMT activity testing new methyl acceptors, potential inhibitors or PNMT activity in adrenal medulla. PMID- 8458903 TI - Simultaneous determination of trimipramine and desmethyl- and hydroxytrimipramine in plasma and red blood cells by capillary gas chromatography with nitrogen selective detection. AB - A simple procedure is described that permits the simultaneous determination of trimipramine and its two major metabolites, desmethyl- and hydroxytrimipramine, in human plasma or red blood cells (RBCs) at therapeutic concentrations. The extracted biological fluids are injected into a capillary gas chromatograph with an OV-1 fused-silica column coupled to a nitrogen-phosphorus-selective detector. The limit of determination for trimipramine is 3 ng/ml and for that desmethyl- and hydroxytrimipramine is 4 ng/ml. The method permits the RBC/plasma ratios to be determined and to be correlated with the clinical response. PMID- 8458904 TI - Stereoselective determination of the active metabolites of a new anti inflammatory agent (CS-670) in human and rat plasma using antibody-mediated extraction and high-performance liquid chromatography. AB - The main metabolites of (+-)-2-[4-(2-oxocyclohexylidenemethyl)phenyl]propionic acid (CS-670), a new pro-drug anti-inflammatory agent of the 2-arylpropionic acid type, have one or two chiral centres arising from reduction of the oxocyclohexylidene moiety in addition to an original chiral centre in the propionic acid moiety. To determine these metabolites stereoselectively, antibody mediated extraction was investigated as a stereoselective clean-up method prior to chiral HPLC. Immunoglobulin G, which recognizes each stereoisomeric cyclohexanol moiety, was coupled to cyanogen bromide-activated Sepharose 4B to prepare re-usable immobilized antibody, and its specificity was improved by examination of a washing process after charging of samples. Plasma extracted with the immobilized antibody column was derivatized with a chiral reagent to separate the enantiomers of the propionic acid moiety by HPLC. This newly developed analytical method clarified the stereoselective biotransformation of the pro-drug to pharmacologically active forms in humans and rats related to reduction of the oxocyclohexylidene moiety and chiral inversion in the propionic acid moiety. PMID- 8458905 TI - Determination of p-chloronitrobenzene and its metabolites in urine by reversed phase high-performance liquid chromatography. AB - A simple, accurate and precise isocratic reversed-phase high-performance liquid chromatographic method (HPLC) using ultraviolet detection was developed for the determination of p-chloronitrobenzene (p-CNB) and seven of its metabolites in rat urine. Analysis was performed before and after hydrolysis of the urine samples with acid to determine both free and conjugate forms of the metabolites. An equal volume of methanol was added to the urine sample and after centrifugation the mixed solution was injected into a high-performance liquid chromatograph. A column packed with 5-microns octadecylsilane (ODS) spherical particles was used at 30 degrees C. The metabolites were divided into three groups, and each group was subjected to three different mobile phase and detection wavelength conditions as follows: water-methanol (60:40, v/v) and 250 nm for p-CNB and 2,4 dichloroaniline; 0.005 M phosphate buffer (pH 3.6)-methanol (76:24, v/v) containing 1.2 mM sodium 1-octanesulphonate and 240 nm for p-chloroaniline, 2 chloro-5-nitrophenol, 2-amino-5-chlorophenol, p-chloroacetanilide and 4-chloro-2 hydroxyacetanilide; and 0.005 M phosphate buffer (pH 6.0)-methanol (80:20, v/v) and 340 nm for N-acetyl-S-(4-nitrophenyl)-L-cysteine. The response was linear at concentrations less than 200.0 micrograms/ml (r = 0.9998) for all metabolites, and the detection limits of each metabolite were between 0.05 and 0.2 micrograms/ml in non-hydrolysed urine. Analysis of the spiked samples demonstrated good accuracy and precision of the method in both intra- and inter day assays. Storage stabilities of p-CNB and its metabolites at -20 degrees C, 4 degrees C and room temperature were examined for both neutral and acidic urine samples. This method was also shown to be applicable to toxicokinetic study of p CNB following administration to rats. PMID- 8458906 TI - Determination of methyl 5-hydroxy-2-benzimidazole carbamate in urine by high performance liquid chromatography with electrochemical detection. AB - A high-performance liquid chromatographic (HPLC) assay for methyl 5-hydroxy-2 benzimidazole carbamate (5-HBC) in urine was developed in order to assess the exposure of workers to the pesticide carbendazim. 5-HBC is measured in urine after hydrolysis, sample clean-up through a strong cation-exchange (SCX) column and extraction with ethyl acetate. HPLC with electrochemical detection provides selective and sensitive determination of 5-HBC with a detection limit of 5 micrograms/l. A C18 reversed-phase column was used with 0.06 M ammonium acetate solution (pH 8)-methanol (73:27) as mobile phase. The method was validated with respect to hydrolysis of urine samples, analytical recovery of spiked 5-HBC, stability of 5-HBC conjugates, limit of detection, background and precision. The overall analytical recovery from urine was better than 60%. 5-HBC, excreted in urine as a conjugate, was stable for at least one year when stored at -20 degrees C. A background of ca. 5 micrograms/l was detected in urine from some non occupationally exposed persons. Between-day coefficients of variation as calculated from the results of the stability test were 7, 4 and 4% for concentrations of 61, 244 and 295 micrograms/l 5-HBC, respectively (n = 16). PMID- 8458907 TI - Analysis of polyols in uremic serum by liquid chromatography combined with atmospheric pressure chemical ionization mass spectrometry. AB - Liquid chromatography with atmospheric pressure chemical ionization mass spectrometry in the negative-ion mode was used to analyse polyols in uremic serum obtained from haemodialysis patients. With post-column addition of 1% chloroform methanol as an ionization accelerating solvent, the chloride addition ions, [M+Cl]-, were detected as base peaks, and the molecular masses of the polyols were easily determined by comparing [M+Cl]- and [M - H]- ions. Concentrations of erythritol, myoinositol, mannitol and sorbitol were markedly increased, and that of 1,5-anhydroglucitol was markedly decreased in the uremic serum compared with normal serum. After haemodialysis, the serum concentration of these polyols decreased significantly. This method was found to be useful in analysing the profile of polyols. PMID- 8458908 TI - High-performance liquid chromatographic determination of nicotine and its urinary metabolites via their 1,3-diethyl-2-thiobarbituric acid derivatives. AB - The 1,3-diethyl-2-thiobarbituric acid (DETBA) assay for nicotine metabolites has been improved so that it can be used to determine the concentrations of nicotine and up to 12 metabolites in the urine of humans and laboratory animals, including phase 2 metabolites. The products of beta-glucuronidase cleavage found in human urine were mainly trans-3'-hydroxycotinine, cotinine, and a small amount of nicotine. Following isolation, spectroscopic analyses showed the structure of the nicotine DETBA derivative to be the one-to-one ring-opening product of DEBTA and the cyanopyridinium salt of nicotine. PMID- 8458909 TI - Effect of xenobiotics on quinone reductase activity in first trimester explants. AB - The placental protective enzyme quinone reductase (QR) has recently been reported to be induced by exposure to mercury, which is a toxic metal in vitro at term. In the present study we have examined the effect of three groups of xenobiotics carcinogens, chemoprotectors and a natural antioxidant, ascorbic acid (vitamin C) on this enzyme activity in the first trimester placenta in vitro. Incubations with the carcinogen benzo[a]pyrene (BP) at 10-50 microM doses increased the enzyme activity at 6 h. At 24 h the effect of 10 microM BP was significant while that of 50 microM BP was not consistent. On the other hand the effect of 50 microM 3-methylcholanthrene at both time points was not significant. Ascorbic acid (5-25 microM) added for 24 h caused a 2- and 4-fold increase in the enzyme activity, respectively (P < 0.005). Exposure to a 25 microM concentration of different classes of chemoprotectors 2(3)-tert-butyl-4-hydroxyl-anisole (BHA), dicoumarol and Sudan I caused a 2.5- to 3.6-fold significant increase in the enzyme activity after 24 h (P < 0.01). Present data suggest that QR activity in the early placenta is responsive to a wide variety of xenobiotics in vitro. Vitamin C in concentrations usually consumed, exerted a potent effect on local QR activity in vitro which may protect pregnant women and their conceptus in an adverse environment. PMID- 8458910 TI - Effect of 1-34 human parathyroid hormone upon first trimester placental human chorionic gonadotrophin secretion in vitro: potentiation by epidermal growth factor. AB - Human chorionic gonadotrophin (HCG) secretion by the early placenta is under multifactorial control. Epidermal growth factor (EGF) has been reported to be involved in regulating the formation and secretion of HCG by first trimester placental explants in culture. The effect of the amino-terminal fragment of parathyroid hormone (1-34 PTH), a calciotrophic factor upon HCG secretion, and its possible interaction with EGF were examined in this study, both in static cultures and in superfusion, where it has previously been demonstrated that HCG secretion is spontaneously pulsatile. Gestational age-dependent effects of 1-34 PTH were noted in both models. In static cultures, 1-34 PTH stimulated HCG secretion in 7-9 week placenta, in a biphasic fashion, the maximal effect being noted at 10-25 ng/ml concentrations (250-270%), while at 1 and 100 ng/ml, the effect was mild. In superfusion, the effect of 1-34 PTH added overnight was also stimulatory, as shown by the significantly increased pulse amplitude and area under the curve. Effects of 1-34 PTH at 11-14 weeks were inhibitory. In static cultures at 7-9 weeks, the stimulatory effect of 25 ng 1-34 PTH was increased by 70% when EGF (100 ng/ml) was added. However at 11-14 weeks, this combined effect was inhibitory. We conclude that 1-34 PTH has an endocrine effect on secretion of HCG by the first trimester placental tissue, and this effect is potentiated by the addition of EGF. PMID- 8458911 TI - Placental and ovarian hormones in anembryonic pregnancy. AB - The circulating levels of human chorionic gonadotrophin (HCG), pregnancy associated plasma protein-A (PAPP-A), Schwangerschaft protein 1 (SP-1), oestradiol and progesterone were measured in 81 pregnant patients between 4 and 11 weeks gestation, following in-vitro fertilization and embryo transfer. The patients were divided as follows: singleton anembryonic pregnancies, n = 22; singleton pregnancies which spontaneously aborted following the demonstration of fetal heart activity, n = 7; and normal singleton pregnancies, n = 52. The levels of all substances measured were significantly reduced in women with anembryonic compared to those with singleton pregnancies which proceeded to term. The serum levels of SP-1, weeks 6-8 (P < 0.01); HCG, weeks 6-8 (P < 0.05); oestradiol, weeks 5-8 (P < 0.05) and progesterone, weeks 6-8 (P < 0.05), were lower in anembryonic pregnancies than in those of pregnancies which spontaneously aborted. These differences may be a reflection of the fact that miscarriage, after the demonstration of fetal heart activity, represents fetal demise at a later stage in pregnancy. In anembryonic pregnancies, significant associations were found between HCG and both oestradiol and progesterone levels from weeks 6 and 8, suggesting that in the absence of an embryo, HCG is the prime determinant of steroid synthesis by the corpus luteum. PMID- 8458912 TI - Heterotopic pregnancies after in-vitro fertilization and embryo transfer--a Danish survey. AB - Thirteen cases of heterotopic pregnancy were diagnosed among 1171 pregnancies established in Denmark after in-vitro fertilization and embryo transfer (IVF-ET). Thus the frequency of heterotopic pregnancy was 13/1171 or 1.1%. In five cases the diagnosis of heterotopic pregnancy was made by ultrasound at 6-9 weeks of gestation; three of these patients were asymptomatic, while two patients presented with abdominal pain and vaginal bleeding. All these patients had an unruptured ectopic pregnancy. Eight cases were diagnosed at the time of surgery; all these patients presented with abdominal pain. Only two of the 13 patients had vaginal bleeding. In nine of the 13 cases the intra-uterine pregnancy resulted in term delivery, while one pregnancy is ongoing. In pregnancies following IVF-ET, this diagnosis should particularly be considered in cases with abdominal pain; vaginal bleeding may be absent. Ultrasound examination may lead to early diagnosis even in asymptomatic cases. In most cases, removal of the ectopic gestation will allow the intrauterine pregnancy to proceed to term. PMID- 8458913 TI - Changes in adrenergic receptors in the pregnant human uterine cervix following mifepristone or placebo treatment in the first trimester. AB - There is increasing evidence that the antiprogesterone mifepristone (RU-486) can dilate the cervix of pregnant women. The uterine and cervical smooth muscle contractile response to adrenergic agonists is regulated by the steroidal environment. This study was undertaken to assess the effects of treatment with RU 486 on the concentrations of alpha- and beta-adrenoceptors in cervical crude membranes from pregnant women using a radioligand binding assay. A special needle biopsy technique was used for human cervical specimens. The probable relative oestrogen dominance due to the antiprogesterone treatment selectively decreased the alpha-2 adrenoceptor in human cervix at an early stage of gestation. This finding was similar to that reported earlier in pregnant rabbits. The existence of a functionally distinct alpha-2 adrenergic receptor subtype will have important implications for our understanding of the contractile activity of the cervix. PMID- 8458914 TI - Reproductive performance of women with uterine malformations. AB - The fertility problems of 176 patients with uterine malformations [arcuate (n = 40), bicornuate (n = 49), bicornis-bicollis (n = 17), didelphys (n = 15), unicornuate (n = 24), subseptus (n = 14) and septate uterus (n = 17)] and of 28 women with other genital and/or urinary anomalies but with a normal uterus were studied. Ten patients with a uterine anomaly experienced infertility without other causes (6%). 142 women with uterine malformations and 26 with a normal uterus achieved pregnancy, the total number of pregnancies to date being 383 and 47 in these groups respectively. The outcome of the first pregnancy from women with uterine malformations was similar to that of all pregnancies though less significant. Only 53% of pregnancies in women with uterine malformations ended with a child surviving > 7 days, compared to 89% in women with a normal uterus. The poorest viability results were found in the bicornuate (40%) (47% of pregnancies in this group ended in early abortions), arcuate (45%) and septate uterus groups (59%). The rates of children surviving > 7 days were around 70% in the bicornis-bicollis, didelphys, unicornuate and subseptus uterus groups. Metroplasty in four cases corrected the infertility or repeated abortions in three patients. Cerclages (21) in 14 women increased the live birth rate from 21 to 62%. These results confirm earlier reports that patients with uterine malformations have higher rates of reproductive loss, pre-term delivery, breech presentation and complications that increase obstetric intervention and perinatal mortality. Moreover in our study, pregnancy outcome was poorer in the bicornuate and arcuate uterus groups than in the septate group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458915 TI - A monozygotic twin pregnancy after application of zona rubbing on a frozen-thawed blastocyst. AB - Assisted hatching techniques enhance the success rate of implantation of in-vitro fertilized human embryos. We report here the successful transfer of a frozen thawed human blastocyst on which we applied a non-invasive zona rubbing technique (reduction of the thickness of the zona pellucida by gentle rubbing with a microneedle). The implantation in the uterus led to the delivery of healthy monozygotic twins. PMID- 8458916 TI - Lasers in infertility. AB - Lasers have been used in fertility surgery for the past two decades. This article reviews the development of different wavelength lasers, the different tissue effects and their applications in infertility surgery. The CO2 laser remains the most precise laser, especially in the ultrapulse mode, for the division of adhesions and the accurate and safe vaporization of deposits of endometriosis. The neodymium:YAG laser, because of its greater depth of penetration, is more suited to hysteroscopic surgery, and attempts to focus the energy by sapphire tips and sculpted quartz fibres merely enable tissue to be incised by a thermal effect. Carbon dioxide laser energy is strongly absorbed by the water molecule and is rendered ineffective in the presence of blood so the visible light lasers, argon and potassium titanyl phosphate (KTP/532) lasers, are more suitable for the treatment of ovarian endometriomas and ectopic pregnancies. Techniques and results of laser surgery in endometriosis, tubal surgery, ectopic pregnancy and polycystic ovarian syndrome are reviewed. The main advantage of the various lasers is that they allow fertility surgeons to perform operative surgery by the minimally invasive approach of laparoscopy rather than laparotomy. PMID- 8458917 TI - Embryo transfer and related techniques in domestic animals, and their implications for human medicine. AB - This report was commissioned by the Canadian government on the relevance of new techniques in animal embryology to the social, ethical and clinical applications of assisted human reproduction. It briefly describes the history of animal breeding, and the regulation of the female reproductive tract, ovulation and fertilization in laboratory and veterinary species. Embryo transfer is described in detail, including the synchronization of reproductive cycles, superovulation and embryo growth in vitro. Methods of experimental embryology, including bisection, sexing of spermatozoa and embryos, cloning and gene therapy are described. The relevance of these studies to human IVF are considered briefly. PMID- 8458918 TI - A critical appraisal of assisted reproduction techniques. AB - Several treatments for infertility have been promoted with only little supporting objective data demonstrating their therapeutic value. The choice of an assisted reproductive technique depends on a balance between numerous factors. Seldom is the choice absolute as in patients with tubal block. There is conflicting evidence on the efficacy of simpler methods such as ovarian stimulation with or without artificial insemination and the available data suggest that the more invasive methods such as gamete intra-Fallopian transfer or in-vitro fertilization are more effective in the treatment of couples with unexplained infertility. Equally, there is no conclusive evidence that pregnancy rates with any of the invasive techniques are superior to any others. However, a higher implantation rate following tubal embryo transfers is observed in many studies. This review presents a critical assessment of the effectiveness of assisted reproductive techniques. PMID- 8458919 TI - Immunohistochemical staining of von Willebrand factor in human endometrium during normal menstrual cycle. AB - Endometrial biopsies were obtained from 73 normal women throughout the menstrual cycle. Using a polyclonal antibody and a streptavidin-biotin-peroxidase method, formalin-fixed paraffin sections of the tissue were stained for von Willebrand factor (vWF). Both subjective scoring and objective quantitative colour image analysis were used to assess the staining intensity, and the results obtained by the two methods were in concordance with each other. Positive staining was observed at all stages of the menstrual cycle. Specific staining was confined to the vascular endothelium and showed cyclical changes. The staining intensity was the weakest during the menstrual phase and was significantly (P < 0.02) reduced from all other stages of the cycle, except late secretory phase. This was followed by a rapid increase in the early proliferative phase to reach a peak in the mid cycle before gradually falling off towards the end of the cycle. The staining intensity in the late secretory phase was significantly reduced (P < 0.05) from other stages except menstrual, early proliferative and mid secretory phase. Vascular staining for vWF was heterogeneous with some vessels devoid of any positive staining. PMID- 8458920 TI - Biometrical evaluation in fertility studies. PMID- 8458922 TI - Overstimulated cycles under low-dose gonadotrophins in patients with polycystic ovary syndrome: characterization and management. AB - Among 30 patients with polycystic ovary syndrome, treated with low-dose gonadotrophins, 75 cycles were analysed in order to characterize overstimulated cycles that were at increased risk of developing ovarian hyperstimulation. Optimal response (one or two follicles > or = 14 mm diameter) was observed in 59 cycles (79%). The remaining 16 cycles (21%) exhibited an overstimulated response characterized either by growing more than two follicles or having an oestradiol level > 850 pg/ml (2 SD above the mean observed in optimal cycles). Six of the latter were handled prospectively when oestradiol levels were found to be too high according to the size of the leading follicle. This stage was termed as developing overstimulation and its identification was based on objective criteria obtained from the optimal group. Following the withholding of gonadotrophin, the follicles continued to grow; however, the final oestradiol level was lower compared with six other matched overstimulated cycles. Overall, 14 patients conceived (47%) of whom three (21%) had multiple pregnancies. Mild or moderate ovarian hyperstimulation syndrome occurred in three cases; all of which involved overstimulated cycles. Low-dose gonadotrophin treatment is associated with a substantial degree of overstimulated response. All cycles should be monitored carefully in order to recognize the overstimulated response, which deserves cautious management. PMID- 8458921 TI - The expression of cytoskeletal proteins during the differentiation of rat granulosa cells. AB - This report examines the relationship between aromatase activity and progesterone production and the expression of actin and vinculin in rat granulosa cells, exposed to insulin, follicle stimulating hormone (FSH) and human chorionic gonadotrophin (HCG). Granulosa cells of pre-antral follicles from juvenile rats treated with diethylstilbestrol (DES) were cultured on collagen A-coated plastic coverslips in serum-free medium. At a moderate or low level of steroidogenesis (FSH alone), the expression of vinculin was diminished while vinculin plaques disappeared completely. At a high level of steroidogenesis (both FSH and insulin), actin in stress fibre form was also decreased considerably. Under conditions of progesterone production (pretreatment with FSH and subsequent incubation with HCG), a concomitant increase of actin in soluble form was found. It is concluded from these studies that the higher the steroidogenesis level of the granulosa cells, the lower the organization of the microfilaments vinculin and actin, which are regulated independently of each other. PMID- 8458923 TI - Indomethacin in vivo inhibits the enhancement of the progesterone secretion in response to gonadotrophin-releasing hormone by human corpus luteum. AB - Different prostaglandins (PG) seem to have luteolytic or luteotrophic function in relation to the phases of life of the human corpus luteum and in-vitro studies demonstrate a luteotrophic function of PGE2, PGI2, PGD2. The present study evaluated the effect of an inhibitor of prostaglandin synthesis on the hypophyseal and luteal responses to gonadotrophin-releasing hormone (GnRH) in women during the mid-luteal phase. Twenty normal menstruating women participated in the study. Two different protocols were applied. After monitored ovulation (day 0), eight patients were treated with indomethacin for 7 days and 12 untreated patients served as controls. To evaluate luteal progesterone production, blood samples were taken every 15 min for 2 h basally and after a bolus of GnRH (25 micrograms i.v.); eight control patients were also treated with indomethacin for one day, and the endocrine study was repeated. The long-term administration of indomethacin significantly reduced basal as well as luteinizing hormone (LH)-stimulated progesterone production by the corpus luteum in respect to controls. Short-term administration failed to influence basal progesterone production, but abolished its secretory response to LH. A luteotrophic role for prostaglandins in human luteal function is suggested. PMID- 8458924 TI - A prospective randomized study on oestradiol valerate supplementation in addition to intravaginal micronized progesterone in buserelin and HMG induced superovulation. AB - A prospective randomized study was conducted to evaluate the use of adding oestradiol valerate 6 mg per os daily to intravaginal micronized progesterone (600 mg daily) as luteal supplements. The study comprised 378 infertile women superovulated with a gonadotrophin releasing-hormone agonist (GnRHa) and human menopausal gonadotrophins (HMG) for in-vitro fertilization (IVF) or zygote intra Fallopian transfer (ZIFT). The clinical pregnancy rate was similar (29%) whether or not oestradiol valerate was added to intravaginal progesterone. Eighteen out of twenty-two endometrial biopsies were in phase, and morphological evaluations of the two luteal supplementation groups were not different. Serum hormone profiles in singleton pregnancies showed a similar day of appearance of human chorionic gonadotrophin (HCG) in both protocols but significantly lower oestradiol concentrations arose in the group without oestradiol valerate. In 32% of the singleton pregnancies, the first appearance of HCG occurred later than day 12 after HCG injection; in those ongoing pregnancies, corpus luteum rescue--as measured by significantly lower serum oestradiol and progesterone concentrations- was compromised. This study provided no evidence of any benefit of routinely supplementing GnRHa/HMG cycles with oestradiol valerate in addition to intravaginal micronized progesterone. PMID- 8458925 TI - Increasing progesterone secretion in human granulosa-luteal cells induced by human follicular fluid. AB - Increasing evidence suggests that local ovarian agents play a central role in the regulation of follicular maturation and corpus luteum formation. In previous studies, we have shown that porcine follicular fluid induces granulosa cell luteinization in sow, human and rat. In the present study, the effect was investigated of either human follicular fluid (FF) alone, human follicle stimulating hormone (FSH) alone, or both upon progesterone secretion of human granulosa-luteal cells. Granulosa-luteal cells were cultured in the presence of either FSH (5, 50 and 250 ng/ml), lyophilized FF (50 and 250 micrograms/ml) or both. Secretion of progesterone increased from a minimum of 2.5-fold to a maximum of 23-fold in the presence of FSH alone and, significantly less (approximately 2 fold) in the presence of FF alone, compared to cells cultured in medium alone. The co-administration of FSH and FF was significantly more effective than either alone, while addition of both FSH (250 ng/ml) and FF (250 micrograms/ml) gave maximal progesterone secretion. In granulosa-luteal cells pre-cultured with both FSH and FF, subsequent exposure to human chorionic gonadotrophin (HCG) alone increased progesterone secretion 1.6-fold to 11-fold, compared to cells pre cultured with FSH alone. The effect of FF from individual follicles was also studied. FF from follicles yielding mature cumulus-oocyte complexes was 4.2-fold more effective, than FF obtained from follicles yielding immature cumulus-oocyte complexes in enhancing the FSH stimulation of progesterone secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8458926 TI - Patient history as a simple predictor of pelvic pathology in subfertile women. AB - The objective of this study is to determine in a group of subfertile women whether patient history can differentiate women with a healthy pelvis from those with endometriosis or adnexal adhesions. In this prospective study, consecutive subfertile women undergoing laparoscopy and tubal hydrotubation for the sole indication of subfertility were evaluated at the teaching hospital fertility unit. They had a minimum of 2 years subfertility. The main outcome measures were: patients' response to a 7-point physical symptom and medical history questionnaire, laparoscopic findings of endometriosis and adnexal adhesions quantified according to the American Fertility Society classification. Of 104 patients, 99 patients were retained in the analysis. Forty per-cent had endometriosis, 19% pelvic adhesions and 40% a normal pelvis. Severe dysmenorrhoea was the only symptom predictive for endometriosis (relative risk 1.7). Severe dysmenorrhoea, a vaginal discharge, past use of a coil and previous laparotomies were all predictive for pelvic adhesions (relative risks 2.1, 3.3, 2.1, 1.9, respectively). The relative risk increased with severity of the disease. Patients with moderate and severe adhesions were 4.2 and 5.3 times more likely to have severe dysmenorrhoea and a vaginal discharge than patients with a normal pelvis. Subfertile women giving a positive response to selected questions about their medical history are at increased risk of endometriosis and pelvic adhesions. Where resources are limited, such a system could be used to plan effective use of available diagnostic facilities. PMID- 8458927 TI - Sequential clomiphene citrate and human menopausal gonadotrophin for ovulation induction: comparison to clomiphene citrate alone and human menopausal gonadotrophin alone. AB - The need for frequent injections and monitoring, the possibility of multiple gestations, and the higher cost compared to clomiphene citrate, prevents many clinicians from using human menopausal gonadotrophin (HMG) for ovulation induction. A sequential medication regimen, in which HMG is taken after clomiphene, overcomes these problems. We retrospectively compared per cycle fecundity and birth rates in 119 cycles of clomiphene-HMG, 524 cycles of clomiphene alone, 57 cycles of HMG alone, and 79 cycles of concurrent HMG and clomiphene in patients receiving intra-uterine insemination (IUI), who were free of endometriosis or tubal disease. Per cycle fecundity for clomiphene-HMG was 22% [95% confidence interval (CI) 12-34%], double that of clomiphene alone (11%) (95% CI 8-14%) (P < 0.01), and equal to HMG alone (18%) (95% CI 7-29%) or HMG and clomiphene together (19%) (95% CI 10-28%). The multiple birth rate for clomiphene HMG (7/21) equalled that for HMG alone (3/12) and HMG and clomiphene together (3/8). The average number of ampoules of HMG required [follicle stimulating hormone (FSH) 75 mIU, luteinizing hormone (LH) 75 mIU] was decreased by 65% from 24.5 +/- 1.0 for HMG or HMG and clomiphene together to 8.6 +/- 0.3 for clomiphene HMG (P < 0.001). Per cycle fecundity was identical when one, two or three ampoules of HMG per day were administered after clomiphene. We conclude that ovulation induction with sequential clomiphene-HMG results in fecundity double that of clomiphene alone and equal to HMG alone or concurrent with clomiphene, thereby reducing the requirement for HMG. PMID- 8458928 TI - Effects of age, gravidity and male infertility status on cumulative conception rates following artificial insemination with cryopreserved donor semen: analysis of 2998 cycles of treatment in one centre over 10 years. AB - The effects of age, gravidity and male infertility status on cumulative conception rates after donor insemination were investigated in an analysis of 2998 treatment cycles undertaken on 443 patients. It was found that the cumulative conception rates after 3, 6 and 12 cycles of treatment were 21, 40 and 62% respectively for patients < 30 years of age compared with 17, 26 and 44% for those aged > or = 30 years (P = 0.008). There was also a significant difference (P < 0.001) in results depending on course of treatment and the cumulative conception rates were 19% after 3 cycles, 33% after 6 cycles and 54% after 12 cycles of treatment in the first course of treatment compared with 40, 67 and 79% respectively in those who returned for subsequent courses of treatment after having achieved a donor insemination pregnancy in the first treatment course. Gravidity and male infertility status (azoospermia or oligozoospermia/asthenozoospermia) did not significantly affect the cumulative conception rates. PMID- 8458929 TI - Estimating fertility potential via semen analysis data. AB - The aim of this study was to evaluate diagnostic profiles for the assessment of semen analysis data with respect to male fertility potential. Semen samples taken from 208 patients of known fertility and suspected infertility were studied by conventional semen analysis methods. The data throw doubt upon the validity of an approach based on the number of deviations from the normal standard values defined by the World Health Organization. The alternative approach of a specific semen characteristic (particularly morphology) as the major predictor of fertility produced no beneficial results. However, the semen analysis index based on semen volume, sperm count, percentage motility and normal forms resulted in a high accuracy of classification but for only 44% of the cases, with 3% false negatives and 10% false positives using cut-off indices of > or = 0.6 and < or = 1.0 for defining 'fertile' and 'infertile' zones, respectively. In conclusion, it is emphasized that there are a number of specific semen analysis variables, each expressing a different aspect of male fertility potential which, when combined in correct proportion, do provide the optimal evaluation of the male fertility status. However, in order to increase the prognostic potential of the semen sample, new and meaningful parameters must be discovered. PMID- 8458930 TI - The effect of ejaculatory frequency on semen characteristics of normozoospermic and oligozoospermic men from an infertile population. AB - The characteristics were examined of 87 consecutive semen samples obtained from participants of an intra-uterine insemination (IUI) programme. The population investigated comprised 65 normozoospermic, 13 moderately oligozoospermic and nine severely oligozoospermic individuals. The samples were produced after 4 days abstinence for the first IUI and after a further day of abstinence for the second IUI. Semen volume, sperm concentration, total sperm count and total motile sperm count for the whole population decreased significantly between the first and second samples. The characteristics of the second sample were significantly decreased only for the normozoospermic group. PMID- 8458931 TI - Increased oestradiol level in seminal plasma in infertile men. AB - Seminal hormonal patterns in fertile and infertile men were investigated. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, testosterone and oestradiol were assessed by radioimmunoassay, and dehydroepiandrosterone sulphate (DHAS) by bioluminescence assay, on blood and seminal plasma of 23 fertile men and 83 infertile men. For fertile men, mean FSH, LH, testosterone and DHAS concentrations were lower and mean oestradiol was higher in seminal than in blood plasma; prolactin did not differ. For infertile men, mean seminal FSH and LH showed a moderate but significant increase compared with fertile men; testosterone, DHAS and prolactin did not differ but mean seminal oestradiol was significantly increased. Of the infertile men, 53% had seminal oestradiol concentration above the 90th percentile value for fertile men. The meaning of this seminal oestradiol increase is unclear since it is not known whether it is the cause or the consequence of the alteration of spermatogenesis in infertile men. Further studies are required to explore the possible therapeutic implications. PMID- 8458932 TI - Human cervical mucus: relationship between biochemical characteristics and ability to allow migration of spermatozoa. AB - Cervical mucus is produced throughout the menstrual cycle. Sperm migration, however, is possible only during the periovulatory period of the cycle. Cervical mucus is also produced during the amenorrhoeic post-partum period. Post-partum mucus is very similar to luteal phase mucus except that it can allow sperm migration. In this study, mucus samples obtained from all these periods were classified according to their capacity to allow sperm migration. The biochemical characteristics of mucus samples that did (peri-ovulatory and 40% of post-partum samples) and did not (luteal and 60% of post-partum samples) allow sperm migration were then compared. Mucus samples with positive sperm migration showed the highest percentage of water and lowest protein and glycoprotein concentration (per ml of mucus). In addition, post-partum mucus samples with positive sperm migration showed lower concentrations of proteins and glycoproteins than post partum mucus samples that did not allow sperm migration. However, the amount of glycoproteins per mg of protein was similar between post-partum samples that were positive and negative for sperm migration. These data suggest that the carbohydrate composition of the glycoproteins is playing a key role in the ability of cervical mucus to accept spermatozoa. PMID- 8458933 TI - Potential genetic risks of using semen collected during chemotherapy. AB - The results of many studies on the effects of mutagens on germ cells of the testes indicate that the recommendation of Carson et al. (Hum. Reprod., 6, 992 994, 1989) that semen samples collected during chemotherapy and cryopreserved may be safely used for insemination is incorrect because of the large potential for genetic risk to the offspring. Data from experimental animals, which indicate high levels of mutagenic effects in offspring from matings during or soon after treatment of the male with chemotherapy or radiation, are reviewed. The relevance of these data to the human situation is discussed. Based on these results, I recommend that patients not only complete their semen cryopreservation prior to the initiation of chemotherapy, but that they practice reliable contraception from the time of initiation of treatment until 6 months after completion of treatment. PMID- 8458934 TI - In-vitro fertilization in the presence of antisperm antibodies detected by the mixed antiglobulin reaction (MAR) and the tray agglutination test (TAT). AB - Data from 33 couples suffering from male immune infertility, who underwent 47 in vitro fertilization (IVF) cycles between January 1989 and August 1991, were retrospectively analysed. The serum of all the 33 male partners had elevated tray agglutination test (TAT) titres (> or = 1:16) and positive mixed antiglobulin reaction (IgG MAR) test results in their semen. There was a slight correlation between these tests in semen and serum. Fertilization rates were analysed in three sperm MAR subcategories. Only the strongly positive MAR group (values > or = 90%) revealed a significant reduction in fertilization rate compared to the other MAR groups. However, this was not observed with increasing serum TAT titres. Fertilization rates were decreased in asthenozoospermic (20.1%) compared to normozoospermic (34.0%) male partners. This occurred also with couples not affected by immunological factors, but when antisperm antibodies were present, the fertilization rates were significantly poorer irrespective of whether the sperm motility was normal or decreased. Once fertilization occurred, the pregnancy rate was not affected by the severity of immunological factors. In assisted reproduction the sperm preparation techniques may reduce the inhibiting effects of antibodies bound to the spermatozoa, and when there are several oocytes to be inseminated, the chance of fertilization rises. PMID- 8458935 TI - Pregnancy using spermatozoa aspirated from the vas deferens in a patient with ejaculatory failure due to spinal injury. AB - Aspiration of the vas deferens under local anaesthesia was carried out in a man with ejaculatory failure due to tetraplegia after rectal electrostimulation had failed to provide an ejaculate satisfactory for use in in-vitro fertilization. After passage through a discontinuous Percoll gradient and exposure to 3 mmol pentoxifylline and 3 mmol 2-deoxyadenosine, the final preparation consisted of 50,000 spermatozoa with 4% progressive motility. This was sufficient for the insemination of seven of the 23 oocytes that were collected from the patient's wife by transvaginal ultrasound-guided follicular aspiration. Three high-grade embryos were produced which were transferred transcervically into the uterus 2 days later. A singleton pregnancy resulted which is currently ongoing at 30 weeks gestation. Aspiration of the vas deferens is a relatively simple technique which provides an acceptable alternative to rectal electrostimulation, artificial sperm reservoirs and donor insemination in patients with ejaculatory failure. PMID- 8458936 TI - Mammalian fertilization as a biological machine: a working model for adhesion and fusion of sperm and oocyte. AB - This review argues that the phenomena of sperm adhesion to the mammalian oocyte and their subsequent fusion can be better understood in the light of recent developments in cell biology. Cell-cell adhesion is mediated, in general terms, by adhesion molecules and their counter-receptors on adhering membranes, and membrane fusion by fusion molecules. The application of these ideas to mammalian fertilization is examined in detail. It is argued that the adhesion of sperm and oocyte is a complex problem which involves not only mutual recognition, but possibly early reorganization of the oocyte cytoskeleton. Mechanisms for activating cytoskeletal reorganization in the oocyte are identified. The site of fusion on the sperm head is discussed, together with the evidence that PH-30 is the fusion protein. It is suggested that current evidence supports the view that PH-30 is an adhesion molecule which is potentially capable of contributing to the reorganization of the oocyte cytoskeleton at the site of sperm attachment, but that PH-30 may not be the fusion molecule. It is argued that an appropriate conceptual framework in which to view sperm-oocyte adhesion and fusion is that of a biological machine into which the role of individual molecular components can be fitted as they become identified. It is hoped that this framework, together with verifiable ideas taken from other areas of cell biology, may facilitate an understanding of this key area of fertilization. PMID- 8458937 TI - Embryonic morphology and rate of implantation of human embryos following co culture on bovine oviductal epithelial cells. AB - A study was undertaken to evaluate embryonic development and establish pregnancies with human embryos after in-vitro culture in two different systems. Treatment A consisted of culturing zygotes in serum-supplemented human tubal fluid culture medium (HTF). Treatment B consisted of culturing zygotes on a monolayer of bovine oviductal epithelial cells with HTF. At the time of embryo replacement, embryos in treatment B had 4.11 blastomeres present, which was greater (P < 0.05) than the 3.81 present for embryos in treatment A. In addition, the cellular fragmentation rate for treatment A embryos was 1.10, which was greater (P < 0.05) than the fragmentation rate of 0.38 for embryos within treatment B. The incidence of ongoing pregnancy was higher after replacement of co-cultured embryos (treatment B) (43%) than replacement of conventionally cultured embryos (treatment A) (29%). The implantation rate per embryo increased (P < 0.05) from 11.5 to 18.4% after co-culture. In treatment B the proportion of 'spare' embryos developing to expanded blastocysts was 58.5%, which was greater (P < 0.05) than the blastocyst development rate of 29.3% observed for embryos within treatment A. PMID- 8458938 TI - Use of disinfectants to reduce microbial contamination of hubs of vascular catheters. AB - The vascular catheter hub is a potential portal of entry for microorganisms that cause catheter-related sepsis. Thus, a reduction in catheter hub contamination might reduce the incidence of catheter-related sepsis. To develop a regimen suitable for reducing microbial contamination of the catheter hub, we experimentally contaminated catheter hubs and assessed the efficacies of disinfectant solutions. Catheter hubs were incubated overnight with suspensions of Staphylococcus epidermidis, Pseudomonas aeruginosa, or Candida parapsilosis. After removal of unattached microorganisms, the catheter hubs were swabbed by rotating cotton swabs dipped in 1% chlorhexidine, 1% chlorhexidine in 70% ethanol, 70% ethanol, 97% ethanol, or normal saline. Posttreatment swabs of the catheter hub were obtained and cultured quantitatively. The cleaning regimens containing ethanol were the most effective. Seventy percent ethanol was more effective than chlorhexidine and is likely to be the safest treatment. We conclude that cleaning of the catheter hub with disinfectant can dramatically reduce microbial contamination. PMID- 8458939 TI - Pseudomonas aeruginosa folliculitis acquired through use of a contaminated loofah sponge: an unrecognized potential public health problem. AB - Pseudomonas aeruginosa folliculitis is a well-known entity that occurs among users of closed-cycle recreational water sources such as whirlpools, swimming pools, and hot tubs. In the absence of this epidemiologic link, isolated cases are difficult to diagnose. We encountered a patient who developed P. aeruginosa folliculitis subsequent to the use of a loofah sponge grossly contaminated with the same P. aeruginosa strain (serotype 10; pyocin type 1/a 4,b) that was recovered from her skin lesions. Furthermore, we demonstrated that sterile unused loofah sponges can serve as the sole growth-promoting substrate for P. aeruginosa. To obviate the potential public health problem of contaminated loofah sponges, it is strongly recommended that manufacturers append, and consumers adhere to, instructions as to the care of loofah sponges, which includes allowing the sponge to dry after use. PMID- 8458940 TI - Enteric adenovirus infection among infants with diarrhea in rural Bangladesh. AB - A total of 4,409 stool specimens from infants less than 5 years of age seeking treatment for diarrhea in Matlab, Bangladesh, were tested for the presence of adenoviruses by using an enzyme immunoassay (EIA). EIA-positive stool samples were serotyped with monoclonal antibodies specific for adenovirus type 40 (Ad40) and Ad41 and group antigen, inoculated into Graham G293 cells, and retested by EIA. Of adenovirus-positive cultures, 125 (2.8%) specimens were confirmed as enteric adenoviruses (EAds), of which 51 (40.8%) were typed as Ad40 and 74 (59.2%) were typed as Ad41, and 12 of 4,409 (0.3%) were identified as nonenteric adenoviruses. A slight peak of incidence of EAd infection was observed in the cool, dry months, and an outbreak of Ad40 infections occurred in March 1988, when the detection rate of EAd reached 12.3%. Information on age, gender, and symptoms was available for 80 infants infected with adenovirus only. Age distribution was similar for types 40 and 41 and nonenteric adenovirus; the median ages were 11, 12, and 12 months, respectively. The ratio of males to females for the 80 infants varied according to serotype; Ad40 had the highest male/female ratio, 2.17. The symptoms experienced by the 80 children were similar for each adenovirus type. The most common clinical features of EAd infection were watery diarrhea (87.5%), more than eight loose bowel movements per day in the 24-h period prior to presentation (68.8%), with vomiting (80.0%), abdominal pain (76.3%), and low grade fever (95.0%); these symptoms are significantly similar to symptoms of infants infected with group A rotavirus. EAd infection generally gave rise to mild to moderate dehydration, which is significantly similar to dehydration produced by infection with rotavirus. PMID- 8458941 TI - Numerical approach to reference identification of Staphylococcus, Stomatococcus, and Micrococcus spp. AB - A numerical-code system for the reference identification of Staphylococcus species, Stomatococcus mucilaginosus, and Micrococcus species was established by using a selected panel of conventional biochemicals. Results from 824 cultures (289 eye isolate cultures, 147 reference strains, and 388 known control strains) were used to generate a list of 354 identification code numbers. Each six-digit code number was based on results from 18 conventional biochemical reactions. Seven milliliters of purple agar base with 1% sterile carbohydrate solution added was poured into 60-mm-diameter agar plates. All biochemical tests were inoculated with 1 drop of a heavy broth suspension, incubated at 35 degrees C, and read daily for 3 days. All reactions were read and interpreted by the method of Kloos et al. (G. A. Hebert, C. G. Crowder, G. A. Hancock, W. R. Jarvis, and C. Thornsberry, J. Clin. Microbiol. 26:1939-1949, 1988; W. E. Kloos and D. W. Lambe, Jr., P. 222-237, in A. Balows, W. J. Hansler, Jr., K. L. Herrmann, H. D. Isenberg, and H. J. Shadomy, ed., Manual of Clinical Microbiology, 5th ed., 1991). This modified reference identification method was 96 to 98% accurate and could have value in reference and public health laboratory settings. PMID- 8458942 TI - Polymerase chain reaction for detection of Mycobacterium leprae in nasal swab specimens. AB - The polymerase chain reaction based on the selective amplification of a 531-bp fragment of the gene encoding the proline-rich antigen of Mycobacterium leprae was applied to nasal swab specimens from leprosy patients, occupational contacts, and endemic and nonendemic controls. To prevent false-positive amplification, we used dUTP and uracil-DNA-glycosylase in all polymerase chain reactions. False negative reactions were detected by using a 531-bp modified template as an internal control. Amplification products were found in 55% of untreated patients, in 19% of the occupational contacts, in 12% of endemic controls, and in none of the nonendemic controls. This study strongly suggests that not only leprosy patients but also healthy persons may carry M. leprae. We concluded that polymerase chain reaction is a reliable method to detect M. leprae in nasal specimens. The method holds promise for studying the spread and transmission of M. leprae within a population. PMID- 8458943 TI - Specific detection of toxigenic strains of Clostridium difficile in stool specimens. AB - Clostridium difficile is the infectious agent responsible for antibiotic associated colitis. We report the use of the polymerase chain reaction technique to identify toxigenic strains of C. difficile in human stool specimens. A set of primers based on the nucleotide sequence of the toxin B gene, which amplified a 399-bp fragment from isolates producing toxin B, was designed. We examined 28 known toxigenic strains, which were all positive by this assay. DNAs from the nontoxigenic strains examined and from strains of Clostridium sordellii and C. bifermentans were not amplified with these primers. The sensitivity of this assay allowed us to identify as little as 10% toxigenic C. difficile cells in the presence of 90% nontoxigenic cells and to detect the toxin B gene in 1 pg of DNA from a toxigenic strain. DNAs extracted from 18 clinical stool specimens that were positive for toxin B by the tissue culture cytotoxicity assay were also positive by this assay. In addition, we detected toxin B sequences in DNA from 2 of 18 stool specimens that were negative for toxin B by the cytotoxicity assay. These two stool specimens were from patients who had a clinical pattern of colitis that was compatible with C. difficile causation. This rapid, sensitive assay will be useful for specific identification of toxigenic C. difficile and for revealing cases that are undetected by analysis of fecal samples for toxin B alone. PMID- 8458944 TI - Genomic fingerprinting of "Haemophilus somnus" isolates by using a random amplified polymorphic DNA assay. AB - The random-amplified polymorphic DNA (RAPD) assay was used to generate DNA fingerprints for 16 isolates of "Haemophilus somnus," and one isolate each of "Haemophilus agni," "Histophilus ovis," "Actinobacillus seminis," Pasteurella haemolytica, and Escherichia coli. The RAPD assay differentiated among "H. somnus" isolates, which shared similarity coefficients of 0.46 to 1.00 on the basis of pairwise comparisons of RAPD markers produced with nine random decamer primers. Three virulent encephalitic "H. somnus" isolates exhibited identical banding patterns, suggesting a common clonal ancestry. The RAPD assay clearly distinguished between the "H. somnus"-"H. agni"-"H. ovis" group and the other bacterial species tested. The results of the present study suggest that DNA fingerprinting of "H. somnus" isolates by the RAPD assay could be valuable in revealing subspecific divisions within this largely unexplored species. PMID- 8458945 TI - Diagnosis of invasive candidiasis by a dot immunobinding assay for Candida antigen detection. AB - A dot immunobinding assay which uses a polyclonal rabbit anti-Candida immunoglobulin G as the primary antibody and colloidal gold coated with goat anti rabbit immunoglobulin G as the secondary antibody for the detection of Candida cytoplasmic antigens is described. It was able to detect as little as 1 ng of total Candida protein per ml when a cytoplasmic extract of Candida albicans was seeded into buffer and 10 ng/ml when the same extract was seeded into pooled human serum. Serial serum samples from four groups of patients were assayed for Candida antigen: (i) 22 patients with candidemia, (ii) 16 patients at high risk for invasive candidiasis, (iii) 3 patients with other deep mycoses, and (iv) 50 hospitalized patients at low risk for serious Candida infection. Of the 22 candidemic patients, 19 had invasive candidiasis and 3 had transient candidemia. Antigenemia was detected in 16 of the 19 patients with invasive candidiasis (including patients with C. albicans, Candida tropicalis, Candida glabrata, Candida krusei, and Candida parapsilosis) and in 4 of 16 patients at high risk for invasive candidiasis. There was no detectable antigen in 12 high-risk control patients, 3 patients with transient candidemia, 3 patients with other deep mycoses, and 50 relatively low-risk patients. The sensitivity for detecting invasive disease in candidemic patients and specificity for all patients studied were 84.2 and 94.4%, respectively. The positive predictive value was 80%; the negative predictive value was 95.7%. The sensitivity for neutropenic patients with invasive disease was 85.7%. This assay is rapid and accurate and appears to be useful in identifying candidemic patients with invasive candidiasis. PMID- 8458946 TI - Detection of Mycoplasma pulmonis in experimentally infected laboratory rats by 16S rRNA amplification. AB - Recently, an rRNA-based polymerase chain reaction (PCR) has been developed for the detection of murine mycoplasmas at both the genus and species level (F. J. M. van Kuppeveld, J. T. M. van der Logt, A. F. Angulo, M. J. van Zoest, W. G. V. Quint, H. G. Niesters, J. M. D. Galama, and W. J. G. Melchers, Appl. Environ. Microbiol. 58:2606-2615, 1992). In this study, the diagnostic value of this PCR assay for the detection of Mycoplasma pulmonis in infected rats was studied. For this purpose, 25 Wistar rats were infected intranasally with M. pulmonis strain M72-138 and investigated for the presence of this pathogen by both in vitro isolation and PCR. Five rats were monitored longitudinally by screening of throat swabs at several time points for up to 248 days postinfection. The remaining 20 rats were killed between 3 and 87 days postinfection, and organism recovery from both throat and urogenital tract specimens was attempted. M. pulmonis could be detected in the throat for up to 248 days postinfection but not in the urogenital tract, either by culture or by PCR. PCR proved to be the optimal method for testing throat samples. All samples in which M. pulmonis was detected by culture were also positive by PCR. By PCR, M. pulmonis was also detected in 3.7% of the samples which were culture negative and in 9.9% of the samples from which cultures were overgrown with bacteria. The results of this study demonstrate the suitability of PCR for the detection of mycoplasmal infection in rodents. PMID- 8458947 TI - Polymerase chain reaction-amplified nonradioactive probes for identification of Fusobacterium nucleatum. AB - A polymerase chain reaction probe with 100% sequence identity to 120 deoxyribonucleotides of Fusobacterium nucleatum Fev1, coding for a part of the 40 kDa major outer membrane protein, was labeled with the steroid hapten digoxigenin. The probe was compared with various degenerate oligonucleotide probes and found to tolerate much more stringent washing conditions. It was therefore superior in distinguishing, by means of Southern blots and slot blots, F. nucleatum from other oral gram-negative bacteria in the periodontal pocket and from other fusobacterial species and in distinguishing among different strains of F. nucleatum. F. periodonticum was found to be more similar to F. nucleatum than the other fusobacterial species tested. PMID- 8458948 TI - Characterization of a nested polymerase chain reaction assay for detection of parvovirus B19. AB - The characterization and application of a nested polymerase chain reaction (PCR) assay for the detection of human parvovirus B19 DNA is described. The assay was evaluated with 149 diagnostic serum samples (collected up to 150 days after the onset of symptoms) previously tested by dot blot hybridization for B19 DNA and by class-specific capture radioimmunoassays for the detection of B19 immunoglobulin M (IgM) and IgG. B19 DNA was detectable by the PCR in 70% of the sera. There was a statistically significant association between the detection of B19 DNA by PCR and high B19 IgM values (P < 0.005), low B19 IgG values (P < 0.05), and a short interval between onset of symptoms and serum collection (P < 0.005). Serial serum samples, throat swabs, and peripheral blood mononuclear cells collected from 10 individuals during an outbreak of parvovirus B19 were also tested by the nested PCR. B19 DNA was detectable in the throat swabs at the time of the clinical illness and in the peripheral blood mononuclear cell fraction up to the end point of the study 6 months after infection. The location of the B19 DNA could not be determined in cytocentrifuge preparations of peripheral blood mononuclear cells with nonisotopic in situ hybridization and immunolabelling. PMID- 8458949 TI - Direct detection of Bacillus anthracis DNA in animals by polymerase chain reaction. AB - Bacillus anthracis is a soil pathogen capable of causing anthrax. To establish a method for specifically detecting B. anthracis for practical applications, such as for the inspection of slaughterhouses, the cap region, which is essential for encapsulation in B. anthracis, was used in a DNA hybridization study by polymerase chain reaction (PCR). Oligonucleotide primers were designed to amplify a 288-bp DNA fragment within the capA gene by PCR. The amplified DNA sequence specifically hybridized to the DNA of B. anthracis but not to that of other bacterial strains tested. Since this PCR-based method efficiently and specifically detected the capA sequence of bacteria in blood and spleen samples of mice within 8 h after the administration of live B. anthracis, this PCR system could be used for practical applications. By using lysis methods in preparing the samples for PCR, it was possible to amplify the 288-bp DNA segment from samples containing very few bacteria, as few as only 1 sporeforming unit, indicating that the PCR detection method developed in this study will permit the monitoring of B. anthracis contamination in the environment. PMID- 8458950 TI - Multicenter clinical evaluation of a continuous monitoring blood culture system using fluorescent-sensor technology (BACTEC 9240). AB - The BACTEC 9240 (Becton Dickinson Diagnostic Instrument Systems, Sparks, Md.) is a new continuous-monitoring blood culture system that uses internal, fluorescent CO2 sensors. In a multicenter clinical trial, organism yield and times to detection with the prototype BACTEC 9240 system were compared with those of the BACTEC NR 660 system. Equal volumes of blood were inoculated into the bottles included in the study blood culture sets (aerobic and anaerobic 9240 and NR6A and NR7A bottles). A total of 9,391 aerobic and 8,951 anaerobic bottle pairs were inoculated with 9,801 blood specimens. A total of 587 clinically significant positive blood cultures and 415 cases of sepsis were studied. The standard 9240 aerobic bottle detected significantly more Staphylococcus aureus (P < 0.05), coagulase-negative staphylococci (P < 0.01), and total microorganisms (P < 0.001) than the NR6A bottle. The standard 9240 anaerobic bottle detected significantly more coagulase-negative staphylococci (P < 0.001), members of the family Enterobacteriaceae (P < 0.01), and total microorganisms (P < 0.001) than the NR7A bottle. A total of 420 positive cultures were detected in both systems; for 284, the time to detection was equivalent with both systems (within 12 h); for 123, the 9240 system was faster; and for 13, the NR 660 system was faster (P < 0.001). The average times to detection for the 9240 and the NR 660 systems were 20.2 and 27.5 h, respectively. Ninety-nine cultures were positive only in the 9240 system, and 68 cultures were positive only in the NR 660 system (P < 0.02). The 9240 system also detected significantly more episodes of bacteremia (P < 0.001). The false-positive rates for the 9240 and NR 660 systems were 2.2 and 2.3%, respectively. The false-negative rates for the two systems after 5 days of incubation did not differ significantly. The contamination rates for the 9240 and NR 660 systems were 1.9 and 1.5%, respectively (P < 0.05). In conclusion, the prototype 9240 system detected more clinically significant positive blood cultures and did so sooner than the NR 660 system, with the additional advantages of full automation, continuous monitoring, and noninvasive sampling. PMID- 8458951 TI - Septicemia and meningitis caused by Helicobacter cinaedi in a neonate. AB - Helicobacter cinaedi has been most frequently isolated from rectal swabs of homosexual men with proctocolitis. The microorganism is a normal intestinal inhabitant of hamsters. We report a case of septicemia and meningitis by H. cinaedi in a neonate whose mother cared for pet hamsters during the first two trimesters of her pregnancy. The isolate was detected after 3 days of incubation in a Bact/Alert pediatric blood culture vial and an enrichment broth culture of the cerebrospinal fluid. H. cinaedi should be added to the list of unusual fastidious organisms that cause sepsis and meningitis in the newborn. PMID- 8458952 TI - The benomyl test as a fundamental diagnostic method for medical mycology. AB - The fungicide benomyl has long been known to differentially affect major taxonomic groups of fungi. In the present study 163 species or aggregates of closely similar species of medically important fungi and actinomycetes, as well as species commonly isolated as clinical contaminants, were tested to determine their reactions to three concentrations of benomyl. Fungi of basidiomycetous, endomycetous, and microascaceous affinities were highly resistant, including all common yeasts and Geotrichum, Pseudallescheria, Scedosporium, and Scopulariopsis species. Also resistant were fungi of pleosporalean affinities with poroconidial anamorphs, such as Alternaria, Bipolaris, Curvularia, and Exserohilum species. Most other fungi of ascomycetous affinity were moderately to strongly susceptible. Such fungi included dermatophytes; Coccidioides, Blastomyces, and Histoplasma species; Sporothrix schenckii; medically important aspergilli; and "black yeasts." Benomyl testing aided in the provisional identification of nonsporulating mycelia, including common basidiomycetous isolates obtained as contaminants as well as nonsporulating Aspergillus fumigatus from pulmonary sources. PMID- 8458953 TI - High-level expression of a 56-kilodalton protein gene (bor56) of Rickettsia tsutsugamushi Boryong and its application to enzyme-linked immunosorbent assays. AB - The 56-kDa protein of Rickettsia tsutsugamushi, which is located on the rickettsial surface, has been shown to be an immunodominant antigen. The gene that encodes the 56-kDa protein of R. tsutsugamushi Boryong (bor56) was cloned. Sequencing revealed an open reading frame of 1,602 bp encoding 534 amino acids with a molecular weight of 56,803. The 56-kDa protein of R. tsutsugamushi Boryong (Bor56) was expressed as a fusion protein with the maltose-binding protein of Escherichia coli by deleting 252 bp from the 5' end of the open reading frame and subcloning it into the StuI site of pIH821. The recombinant fusion protein was purified by amylose column chromatography for application in an enzyme-linked immunosorbent assay to evaluate the ability of the method to detect the antibody to R. tsutsugamushi in human patient sera. By using sera from 100 patients with scrub typhus and 70 patients with other febrile diseases, a high diagnostic sensitivity (95%) and a high diagnostic specificity (100%) were demonstrated, suggesting the suitability of the recombinant antigen for use as an immunodiagnostic tool. PMID- 8458954 TI - Differentiation of mycobacteria on the basis of chemotype profiles by using matrix solid-phase dispersion and thin-layer chromatography. AB - Because of the rising incidence of clinical mycobacterial infections and the difficulty in identification and characterization of mycobacteria at the subspecies and serovar levels, a technique for differentiation that could be performed quickly and with relatively little equipment and expense was developed. Lysis and fractionation of mycobacteria by matrix solid-phase dispersion followed by thin-layer chromatography were used to produce chemotype profiles of the lipid and glycolipid components of each isolate. Organisms tested included Mycobacterium scrofulaceum, Mycobacterium phlei, Mycobacterium smegmatis, Mycobacterium flavescens, Mycobacterium kansasii, Mycobacterium bovis, 11 isolates of Mycobacterium gordonae, 10 serovars of Mycobacterium avium, and four strains of Mycobacterium paratuberculosis. A relative retention (Rx) value was established for each visible band on the chromatographs by comparison with a band common to all organisms tested. The chemotype profiles produced were different for every separate species and serovar sampled. These findings suggest that matrix solid-phase dispersion and subsequent thin-layer chromatography may have the sensitivity and flexibility to characterize and identify mycobacteria at the species and subspecies levels and potentially to identify clinical isolates of mycobacteria that have been difficult to identify by standard means. The technique has certain advantages over current biochemical, immunologic, and genetic methods because it is relatively simple to perform, is inexpensive, and requires a small amount of bacterial sample. PMID- 8458955 TI - Detection of Aspergillus fumigatus by polymerase chain reaction. AB - Aspergillus fumigatus is an opportunistic nosocomial pathogen causing an often fatal pneumonia, invasive aspergillosis (IA), in immunosuppressed patients. Oligonucleotide primers were used to amplify a 401-bp fragment spanning the 26S/intergenic spacer region of the rDNA complex of A. fumigatus by the polymerase chain reaction (PCR). The primers were highly sensitive and specific: as little as 1 pg of A. fumigatus genomic DNA could be detected, and the primers only amplified DNA from A. fumigatus and not any other fungal, bacterial, viral, or human DNA tested. Using the PCR, we were able to detect A. fumigatus DNA in lung homogenates from immunosuppressed mice experimentally infected with A. fumigatus but not from immunosuppressed uninfected controls. There was 93% correlation between the culture results and the PCR results. In a retrospective clinical study, the sensitivity of the PCR for the detection of A. fumigatus in clinical samples was confirmed by positive amplification in three of three culture-positive respiratory samples from confirmed cases of IA. Because isolation of Aspergillus spp. may reflect contamination and colonization without infection, the feasibility of using the PCR was evaluated by analyzing culture negative samples from both immunosuppressed patients at high risk for IA and immunocompetent patients with other lung infections. Only 2 of 10 patients were culture negative and PCR positive in the high-risk group, and 2 of 7 patients were culture negative and PCR positive in the immunocompetent group. The results indicate that PCR detection might be a valuable adjunct to current laboratory methods to diagnose IA. PMID- 8458956 TI - Possible role of specific immunoglobulin M antibodies to Plasmodium falciparum antigens in immunoprotection of humans living in a hyperendemic area, Burkina Faso. AB - Two seroepidemiological studies were performed in an area of Burkina Faso hyperendemic for malaria to estimate the protective role of immunoglobulin M (IgM) antibodies. Six cross-sectional surveys were carried out on children (ages, < 16 years) in the village of Karankasso. The evolution of antibodies to crude extracts of Plasmodium falciparum (IgG or IgM antisomatic and IgG antiexoantigens) were tested by IFI or enzyme-linked immunosorbent assay and were followed up according to the fluctuations of the parasite densities. Specific IgG antibodies had the same evolution as parasite densities. By contrast, specific IgM antibodies increased when IgG and parasite densities began to decrease (despite a high inoculation rate). A longitudinal survey of 77 children and adults was conducted in another village (Dafinso). In that study, clinical follow up of the selected individuals allowed us to define three groups in the population. Children in group 1 were considered nonimmune (children with one or more malaria attacks). Group 2 was composed of semiimmune children who did not present with any malarial attack during the survey but who had high levels of parasitemia during the transmission period. Group 3 was composed of immunoprotected adults. Specific IgM and IgG antibodies to crude extracts or a recombinant antigen (glutamate-rich protein) of P. falciparum were tested. Specific IgM antibodies were lower in group 1 (nonimmune) than in groups 2 (semiimmune) and 3 (immunoprotected). Furthermore, there was a negative correlation between parasite densities and the levels of specific IgM antibodies. We discuss the possible role of IgM antibodies in the acquisition of immunity to malaria. PMID- 8458957 TI - Comparison of polymerase chain reaction with culture and enzyme immunoassay for diagnosis of pertussis. AB - A polymerase chain reaction (PCR) assay amplifying a segment of a repeated gene element of Bordetella pertussis was compared with culture and enzyme immunoassay (EIA) for the diagnosis of pertussis. The PCR assay was specific for B. pertussis in tests with a panel of other bacteria and with an extensive collection of specimen material from healthy persons and children with respiratory infections other than pertussis. The PCR assay was used in the analysis of 117 nasopharyngeal swabs collected from children at an elementary school at which a pertussis outbreak occurred. Fifty-six (48%) of the 117 swabs were positive, including those for all six culture-positive cases. The PCR method was then applied to analyze another pertussis outbreak. Of 40 nasopharyngeal aspirates taken from 37 clinically susceptible pertussis patients and from three asymptomatic contacts, the PCR identified 18 (45%), including all 3 culture positive and 5 (35%) of the 14 seropositive patients. The most consistent and reliable diagnosis by positive PCR result was observed with those patients experiencing symptoms within 1 to 6 weeks of sample collection. We conclude that PCR is a rapid, sensitive, and specific means of diagnosing pertussis, especially during the first weeks of disease. The assay can be performed with both nasopharyngeal swabs and aspirates. PMID- 8458958 TI - Elimination of contaminating DNA within polymerase chain reaction reagents: implications for a general approach to detection of uncultured pathogens. AB - Analysis based on comparisons of 16S rRNA sequences provides a rapid and reliable approach to identifying human pathogens. By directing oligonucleotide primers at sequences conserved throughout the eubacterial kingdom, bacterial 16S ribosomal DNA sequences of virtually any member of the eubacterial kingdom can be amplified by polymerase chain reaction and subsequently analyzed by sequence determination. Indeed, automated systems for broad-range amplification, sequencing, and data analysis are now feasible and may form the basis of the next generation of automated microbial identification systems. However, identification of pathogens by this strategy is hampered by the frequent contamination of reagents used for the amplification reaction, in particular Taq polymerase, with exogenous bacterial DNA. Here, we describe detailed investigations on the use of 8 methoxypsoralen and long-wave UV light to eliminate contaminating DNA in polymerase chain reaction reagents. The clinical utility of the developed procedure was demonstrated in a case of paucibacillary osteomyelitis, for which no specific bacterial agent had been cultured. PMID- 8458959 TI - Development of the polymerase chain reaction for diagnosis of chancroid. AB - The published nucleotide sequences of the 16S rRNA gene of Haemophilus ducreyi were used to develop primer sets and probes for the diagnosis of chancroid by polymerase chain reaction (PCR) DNA amplification. One set of broad specificity primers yielded a 303-bp PCR product from all bacteria tested. Two 16-base probes internal to this sequence were species specific for H. ducreyi when tested with 12 species of the families Pasteurellaceae and Enterobacteriaceae. The two probes in combination with the broad specificity primers were 100% sensitive with 51 strains of H. ducreyi isolated from six continents over a 15-year period. The direct detection of H. ducreyi from 100 clinical specimens by PCR showed a sensitivity of 83 to 98% and a specificity of 51 to 67%, depending on the number of amplification cycles. PMID- 8458960 TI - Simple colorimetric microtiter plate hybridization assay for detection of amplified Mycobacterium leprae DNA. AB - The detection of amplified products resulting from polymerase chain reactions (PCRs) remains a complicated process. To simplify the detection procedures, we developed a colorimetric microtiter plate hybridization assay for the specific detection of 5'-biotinylated PCR fragments of Mycobacterium leprae DNA. For this assay, an M. leprae DNA capture probe was made and immobilized on the wells of a microtiter plate. Hybridization of the biotin-labeled PCR fragments was detected through enzymatic color development. The resulting optical densities showed a logarithm-linear relationship with the amount of template DNA and corresponded to the intensity of the bands obtained through gel analysis and Southern blotting of the PCR products. The sensitivity of the assay was found to be 125 fg of genomic M. leprae DNA, or 20 lysed bacilli, revealing a detection limit similar to that of agarose gel analysis. The efficient coamplification of human DNA was used as a positive control for the presence of inhibitory substances in clinical material. For detection of human PCR products, a human DNA capture probe was also constructed for the colorimetric assay. This dual setup for hybridization, which thus detected both M. leprae and human DNA PCR products, was useful for ascertaining the presence of inhibiting substances in clinical specimens. All biopsy specimens (n = 10) from untreated patients with leprosy were positive. Apparently, this assay is more sensitive than microscopy, because biopsy specimens from half of the patients were negative upon histopathological examination. Biopsy specimens from three treated patients were negative, as were those from the three patients who did not have leprosy. We conclude that this colorimetric assay can replace agarose gel analysis and Southern hybridization, because it is as sensitive as those methods. Its advantages over conventional gel analysis and Southern hybridization are that it is less cumbersome and more rapid. PMID- 8458961 TI - Immunological response to cell-free antigens of Paracoccidioides brasiliensis: relationship with clinical forms of paracoccidioidomycosis. AB - Sera from patients with the acute (AF) and chronic (CF) forms of paracoccidioidomycosis (PCM) were tested against Paracoccidioides brasiliensis cell-free antigens by Western blot (immunoblot). The CFA preparation contained components ranging in molecular mass from 18 to 102 kDa. The immunoglobulin G (IgG) reactivity profiles were similar for patients with both forms of the disease, and the 43-kDa component was recognized by 100% of the sera. IgM antibodies from the AF- and the CF-PCM sera recognized 21 and 20 components, respectively, the AF-PCM sera reacting preferentially with components with molecular masses above 50 kDa. None of the AF-PCM sera (IgM) reacted with the 43 kDa component, and only 10% of the CF-PCM sera recognized this molecule. The IgA response was more significant in the CF-PCM group than in the AF-PCM group, and the 43- and 74-kDa components were the most reactive ones (about 40% each). Our results showed that the cell-free antigen preparation is very appropriate for the immunoblotting analysis of PCM sera, and they also showed that the detection of IgG anti-gp43 is the best marker for the diagnosis and the following up of patients with the acute or the chronic form of the disease. PMID- 8458963 TI - Five cases of primary amebic meningoencephalitis in Mexicali, Mexico: study of the isolates. AB - Five Naegleria strains isolated from patients with primary amebic meningoencephalitis and one strain isolated from the water of an artificial canal were investigated. All strains were pathogenic for mice when instilled intranasally and showed cytopathic effects in Vero cell cultures. Their growth characteristics (isolation and subculture at 45 degrees C), serological results, and isoenzyme patterns permitted us to identify the six strains as Naegleria fowleri. This is the first time that Naegleria fowleri has been isolated from patients with primary amebic meningoencephalitis in Mexico. PMID- 8458962 TI - Enzyme immunoassay for detection of human immunodeficiency virus-specific immunoglobulin A antibodies. AB - Early diagnosis of human immunodeficiency virus (HIV) infection may be difficult in adults with acute or recent HIV infection and in infants with perinatally acquired HIV. Detection of HIV-specific immunoglobulin A (IgA) antibodies in infant serum by Western blot (immunoblot) has been suggested as a reliable method to identify HIV-infected infants, especially those over the age of 6 months, and as an adjunct to diagnosis of acute HIV infection in adults. We developed a simple enzyme immunoassay for detection of HIV-specific IgA, using standard commercially available reagents. Enzyme immunoassay was comparable to Western blot for detection of HIV-specific IgA in sera from adults (n = 216), older children (n = 49), and infants born to HIV-infected mothers (n = 65). Specificity was 100% and sensitivity ranged from 80 to 92%. IgA-enzyme immunoassay is a simple, highly sensitive method for detection of HIV-specific IgA antibodies and is easily adapted to the standard clinical laboratory. PMID- 8458964 TI - Endocarditis caused by Rochalimaea quintana in a patient infected with human immunodeficiency virus. AB - Rochalimaea quintana and Rochalimaea henselae are closely related, fastidious, gram-negative rickettsiae. Thus far, the spectrum of human Rochalimaea sp. infections has not included endocarditis. We describe a 50-year-old human immunodeficiency virus-positive man who developed endocarditis caused by R. quintana. DNA relatedness studies, which compared our patient's blood culture isolate with known Rochalimaea species, identified the organism as R. quintana. Our report expands the spectrum of Rochalimaea sp. infections and identifies a new infectious cause of endocarditis. PMID- 8458965 TI - Comparison of different methods and cell lines for isolating measles virus. AB - Infectivity titers were determined for seven strains of measles virus by using various methods and cell lines. The use of B95-8 cells in a shell vial assay resulted in the highest infectivity titers. Our data suggest that B95-8 is the cell line of choice for the isolation of measles virus. PMID- 8458967 TI - Correlation of typing methods for Acinetobacter isolates from hospital outbreaks. AB - Four methods, namely, biotyping, cell envelope protein electrophoresis, ribotyping, and comparison of antibiograms, were used for strain identification of Acinetobacter isolates from five outbreaks in hospitals. There was good agreement among the methods for the identification of an index strain, but biotyping and the comparison of antibiograms were the least discriminatory. PMID- 8458966 TI - Culture confirmation of the carrier status of Babesia caballi-infected horses. AB - Culture of horse blood for Babesia caballi identified four carrier horses among nine previously infected horses. Three of the carriers had no detectable parasitemias on stained blood smears, and sera from two carrier horses were complement fixation test negative. Three cultures were continuously cultivated. Cryopreserved fourth-passage B. caballi was successfully reestablished in vitro. Blood from a 10th horse previously subinoculated with blood from a suspected carrier was cultured, with negative results. PMID- 8458968 TI - Production of enterotoxins and toxic shock syndrome toxin by bovine mammary isolates of Staphylococcus aureus. AB - The production of staphylococcal enterotoxin A (SEA), SEB, SEC, SED, and SEE and toxic shock syndrome toxin 1 by bovine mammary isolates of Staphylococcus aureus was evaluated. Enterotoxin secretion was detected by immunodiffusion using specific polyclonal antisera. Of 262 isolates examined, 75 (28.6%) produced one or more toxins. The most common pattern was secretion of both SEC and SED and toxic shock syndrome toxin 1. No isolates secreted SEE, one produced SEA, and seven secreted SEB. PMID- 8458969 TI - Three supplementary diagnostic tests for Campylobacter species and related organisms. AB - We analyzed 307 recent clinical isolates and reference strains of Campylobacter spp., Helicobacter spp., and Arcobacter spp. for arylsulfatase and pyrazinamidase activities and susceptibility to polymyxin B. All isolates studied were identified by DNA dot hybridization prior to testing. Campylobacter concisus, C. sputorum, and Helicobacter fennelliae were positive for arylsulfatase. C. jejuni, C. coli, C. lari, C. upsaliensis, and C. concisus were positive for pyrazinamidase. Only Helicobacter spp. were resistant to polymyxin B. C. fetus subsp. fetus, C. hyointestinalis, C. mucosalis, and Arcobacter spp. were negative in all three tests. The tests were simple to perform and read, and with the exception of C. sputorum biovars, all isolates within a species gave consistently positive or negative results in all the assays. These three phenotypic tests may help refine current methods for phenotypic identification of Campylobacter spp. and related organisms in a reference laboratory setting. PMID- 8458970 TI - Dot immunobinding assay for simultaneous detection of specific immunoglobulin G antibodies to measles virus, mumps virus, and rubella virus. AB - A dot immunobinding assay was used to detect antibodies to measles virus, mumps virus, and rubella virus antigens. Filter paper soaked with serum or whole blood was directly applied to the antigen-coated nitrocellulose sheets. The test was easy to perform, and its results agreed very well with those obtained by standard enzyme immunoassay. PMID- 8458971 TI - Use of the UV ParaLens adapter as an alternative to conventional fluorescence microscopy for detection of Pneumocystis carinii in direct immunofluorescent monoclonal antibody-stained pulmonary specimens. AB - The UV ParaLens light microscope adapter offers a useful and cost-effective alternative to conventional fluorescence microscopy for Pneumocystis carinii identification, particularly in AIDS patients. In a blinded study, in which 153 pulmonary specimens were examined for P. carinii by direct immunofluorescence, 40 of 42 specimens positive by fluorescence microscopy were also positive by ParaLens. No false positives were observed. PMID- 8458972 TI - Prevalence of antibodies to Coxiella burnetii in Japan. AB - We evaluated the prevalence of Coxiella burnetii antibodies in 626 human serum samples (275 from veterinarians, 107 from meat-processing workers, 184 from respiratory-disorder patients, and 60 from healthy humans) by the indirect immunofluorescence test. Of the serum samples examined, 54 (8.6%) and 103 (16.5%) reacted positively to phase I and II antigens, respectively, of C. burnetii. The rates differed for healthy humans and respiratory-disorder patients. Antibody prevalence was high for healthy humans living in close contact with animals (e.g., veterinarians and meat-processing workers). PMID- 8458973 TI - Two cases of Campylobacter mucosalis enteritis in children. AB - Two cases of Campylobacter mucosalis enteritis in children are reported. The patients recovered without antimicrobial therapy. Strains were isolated only by the feces filtration technique. In one child, bactericidal antibodies to the homologous strain were detected in a convalescent-phase serum sample. C. mucosalis should be considered a primary intestinal pathogen. PMID- 8458974 TI - Amplification of Chlamydia trachomatis DNA by ligase chain reaction. AB - Amplification of Chlamydia trachomatis DNA by polymerase chain reaction was compared with amplification by ligase chain reaction (LCR). Both amplification procedures were able to consistently amplify amounts of DNA equivalent to three C. trachomatis elementary bodies. All 15 C. trachomatis serovars were amplified to detectable levels by LCR, and no DNA from 16 organisms potentially found in clinical specimens or from Chlamydia psittaci and Chlamydia pneumoniae was amplified by LCR. PMID- 8458975 TI - Gene encoding zonula occludens toxin (zot) does not occur independently from cholera enterotoxin genes (ctx) in Vibrio cholerae. AB - Of 167 Vibrio cholerae isolates screened for sequences homologous with zonula occludens toxin (zot) or cholera toxin (ctx) genes, 3.0% of non-O1, 100.0% of clinical O1, and 0.0% of environmental O1 strains contained both zot and ctx. zot was present only in strains that were ctx positive; all ctx-positive strains carried zot. The absence of zot-positive, ctx-negative strains suggests ZOT is not an independent virulence factor for V. cholerae, although ZOT may play a role in the pathogenesis of toxigenic strains. PMID- 8458976 TI - Effectiveness of resins in removing antibiotics from blood cultures. AB - The present study evaluates the effectiveness of BACTEC NR-26A resin-containing medium in removing eight antibiotics from blood cultures. Peak concentrations achievable clinically were chosen. All antibiotics were prepared in fresh human blood samples. Blood samples were obtained prior to and at 15 min and 2, 24, 48, and 72 h after inoculation. Aztreonam, ceftriaxone, imipenem, teicoplanin, and ticarcillin were partially removed from blood cultures. PMID- 8458977 TI - Comparison of enterotoxin production, cytotoxin production, serogrouping, and antimicrobial susceptibilities of Clostridium difficile strains isolated from AIDS and human immunodeficiency virus-negative patients. AB - We analyzed and compared Clostridium difficile strains isolated from diarrheic stools of 49 human immunodeficiency virus (HIV)-negative and 50 AIDS patients. Our results suggest that distribution patterns of serogroups are different in these two populations. Serogroup C (which has been previously reported to be very resistant to antimicrobial agents) represents 66.0 and 18.4% of the isolates from AIDS and HIV-negative patients, respectively (P < 0.001); the selection of serogroup C could be explained by multiple antibiotic pressure to which AIDS patients have been subjected. PMID- 8458978 TI - Biotypes and serotypes of Haemophilus influenzae from patients with meningitis in the city of Sao Paulo, Brazil. AB - A total of 1,094 Haemophilus influenzae isolates from cerebrospinal fluid were examined by biochemical and serological means. Most of them belonged to biotype I (70.9%) and to serotype b (99.4%). The relationship of biotypes I and II to the ages of the patients was shown to be significant (P < 0.001). PMID- 8458979 TI - Evaluation of the API Coryne system for identification of Listeria species. AB - The API Coryne system, a commercially available system for the identification of coryneform bacteria, was used to identify 103 strains of Listeria spp. from clinical and environmental sources. All isolates were identified correctly to the genus or species level, although complete characterization also required tests for beta-hemolysis and CAMP reaction. PMID- 8458980 TI - Rapid and specific identification of Yersinia pestis by using a nested polymerase chain reaction procedure. AB - We developed a 4-h nested polymerase chain reaction assay that detected a region of the plasminogen activator gene of Yersinia pestis in 100% of 43 Y. pestis strains isolated from humans, rats, and fleas yet was unreactive with the closely related species Yersinia enterocolitica and Yersinia pseudotuberculosis. PMID- 8458982 TI - Stability of human immunodeficiency virus type 1 antibodies in whole blood impregnated filter papers under various tropical conditions. PMID- 8458981 TI - Properties and type antigen patterns of group B streptococcal isolates from pigs and nutrias. AB - All 59 group B streptococcal cultures isolated from pigs and nutrias reacted with group B-specific antiserum and gave a positive CAMP reaction in the zone of staphylococcal beta-lysin. Most of the cultures were pigmented; all cultures hydrolyzed Na hippurate and utilized salicin, maltose, and saccharose but not esculin, mannitol, or inulin. Fifty-three percent of the group B streptococci from pigs and none of those from nutrias were lactose positive. Serotyping revealed that most of the group B streptococci from pigs were of serotype III and most of those from nutrias were of type Ia/c. Protein c was present as c beta antigen. All group B streptococci were susceptible to penicillin and bacitracin (10 U), and most of the porcine cultures were resistant to tetracycline. According to these results, group B streptococci from pigs and nutrias differ from bovine and human group B streptococci and seem to play no role in cross infections between animals or between animals and humans. PMID- 8458983 TI - VH gene family utilization of anti-acetylcholine receptor antibodies in experimental autoimmune myasthenia gravis. AB - The immunoglobulin heavy chain (VH) gene family usage in experimental autoimmune myasthenia gravis (EAMG) model was investigated by RNA slot blot hybridization using VH gene family specific probes. Anti-acetylcholine receptor (AChR) monoclonal antibodies (mAbs) isolated from susceptible C57BL/6 and resistant BALB/c mice were found to be encoded by VH genes from at least six different families. The Vgam3.8 family was overrepresented in alpha-bungarotoxin blocking mAbs. Expression of cross-reactive idiotypes by anti-AChR mAbs was irrespective of the VH gene family usage. Strain dependent differences in susceptibility for EAMG were not reflected in an aberrant VH gene family usage of anti-AChR mAbs. PMID- 8458984 TI - Monoclonal antibodies against neuroblastoma. Production and preliminary characterization of their specificity. AB - Neuroblastoma (NB) is a common childhood tumor that originates from neuroblasts of the neural crest. In this paper we will describe the production of murine monoclonal antibodies (mAbs) to human NB cell lines. The hybridomas were selected by ELISA and immunofluorescence for antibody binding to multiple human neuroblastoma cultured cell lines, but not to hematopoietic cells and leukemic cells. The mAbs were characterized in terms of their ability to bind to human cell lines and tissues. The IgG2a and IgG2b mAbs may prove useful in the diagnosis of therapy of neuroblastoma. PMID- 8458985 TI - Phagocytosis of myelin by astrocytes in explants of adult rabbit cerebral white matter maintained on Gelfoam matrix. AB - The role of astrocytes in the process of demyelination has been controversial. A culture system in which explants of adult cerebral rabbit white matter were maintained on a Gelfoam matrix was used for evaluating the phagocytosis of myelin by astrocytes without an influx of phagocytic cells derived from actively circulating blood-borne cells. Adult neurons were not viable for more than a few days in these explant cultures, thus resulting in empty myelin sheaths following loss of their axons. After 7 days in vitro, astrocytes, recognized by positivity for glial fibrillary acidic protein by electron microscopic immunocytochemistry, contained numerous membrane-bound vesicles filled with myelin in various stages of degradation. Although the majority of macrophage-like cells were negative for glial fibrillary acidic protein, a minority were positive, in spite of the lack of bundles of intermediate filaments, and were interpreted as astrocytic. Astrocytes were also often positive for glutamine synthetase. This study presents evidence suggesting that astrocytes may actively participate in the phagocytosis and degradation of myelin, a function generally attributed to reactive macrophages. PMID- 8458986 TI - HIV gp120 alteration of DAMA and IL-1 alpha induced chemotaxic responses in human and invertebrate immunocytes. AB - The effects of a synthetic peptide fragment of human immunodeficiency virus gp120 (HIV gp120) on opioid (D-ala2-D-met5 enkephalinamide; DAMA) and interleukin-1 (IL 1) induced chemotactic responses in human granulocytes and monocytes and invertebrate (Mytilus edulis) immunocytes were studied. Both DAMA and IL-1 increased the velocity of cell migration from both species and the response is chemotactic (e.g. directed). Non-treated control cells move randomly or not at all. The addition of gp120 to DAMA or IL-1 treated human granulocytes or monocytes results in a slower movement which is chemokinetic (loss of directionality or random) in nature. A similar phenomenon occurs in the invertebrate immunocytes. If gp120 alone is added, it inhibits the movement of spontaneously active human granulocytes and Mytilus edulis immunocytes. In contrast, it stimulates chemokinesis of spontaneously active human monocytes. These responses occur immediately after addition of the peptide. Based on experiments with the selective calcium channel antagonist nimodipine, it appears that the gp120 causes its effects by irreversible binding to a calcium channel. Our results suggest a universal inhibitory mechanism is occurring since the invertebrate immunocytes must recognize HIV gp120 peptide to result in this effect, possibly through a CD4 or other type of surface determinant. PMID- 8458987 TI - Induction of class I major histocompatibility complex antigens on adult primate retinal neurons. AB - The expression of class I major histocompatibility complex (MHC) antigens was examined on adult monkey and human retinal cells following injury caused by dissociation. In a panning assay, neurons and glia demonstrated a rapid induction of class I MHC antigens following enzymatic dissociation, and expression was sustained on regenerating neurons as well as on glia in culture. Class I MHC antigen expression was also enhanced following optic nerve crush of monkey eyes in vivo. These results suggest that the functions of class I MHC antigens may be relevant to primate CNS neurons and glia following injury. PMID- 8458988 TI - Neonatal pinealectomy impairs murine antibody-dependent cellular cytotoxicity. AB - The pineal gland, through its principal hormone melatonin, is able to modulate different immune functions. We have previously demonstrated that exogenous melatonin induces a significant enhancement of murine antibody-dependent cellular cytotoxicity (ADCC). In order to determine whether the pineal gland plays a physiological role in ADCC regulation, we studied the influence of neonatal pinealectomy on this activity. The results presented here indicate that ablation of the pineal gland during the first week of life significantly reduces ADCC levels in adult mice. This impairment appears around 60 days of age, suggesting that sexual hormones may be involved in the pineal effect. Moreover, the administration of melatonin to pinealectomized mice restores ADCC levels regardless of the hour and seasonal time of injection. On the basis of the data reported here, a physiological regulation of ADCC by the pineal gland can be assumed. PMID- 8458989 TI - Vapors from collodion and acetone in an EEG laboratory. AB - In the many EEG laboratories, the collodion-acetone technique has lost favor because of offensive vapors. We measured vapor concentrations of diethyl ether and acetone, the two principal vapors from this technique, to determine whether they reached toxic levels. We found that diethyl ether vapors usually reached the olfactory threshold, but acetone concentration did not. Neither reached concentrations that were systemically toxic. We then developed an inexpensive, effective method of reducing concentrated vapors during electrode application and removal and documented a significant reduction in vapor concentrations. With this information and with an inexpensive, "in house" vapor extraction system, technologist and patient satisfaction with the collodion method should greatly improve. PMID- 8458990 TI - Hyperventilation and transcranial magnetic stimulation: two methods of activation of epileptiform EEG activity in comparison. AB - In a prospective study, we compared the established method for an activation of epileptiform activity in EEG, hyperventilation (HV), with the recently presented new activational technique of transcranial magnetic stimulation (TMS) in 10 patients with drug-resistant partial epilepsies. Long-term EEG recordings included subdural electrodes in the course of presurgical evaluation. Epileptiform activity was evaluated visually 500 s before, during, and 500 s after stimulation, and the results were compared statistically. TMS was not better than HV: HV caused an activation of the epileptogenic foci in 6 of 10 cases, TMS only in 3 of 10. Seizures could be induced by HV in 2 of 10, by TMS in no cases. In 2 of 10 cases, TMS even caused a significant reduction of epileptiform activity. PMID- 8458991 TI - Regarding the American Electroencephalographic Society guidelines for standard electrode position nomenclature: a commentary on the proposal to change the 10-20 electrode designators. PMID- 8458992 TI - Autonomic nervous system function. AB - Tests of autonomic function for the clinical autonomic neurophysiology laboratory should be noninvasive, sensitive, specific, reproducible, physiologically and clinically relevant, and not be excessively time-consuming. Laboratory evaluation is strongly indicated when the following are suspected: (1) generalized autonomic failure, (2) benign autonomic disorders that mimic life-threatening disorders, (3) distal small-fiber neuropathy, (4) the autonomic neuropathies, (5) sympathetically maintained pain, and (6) the postural orthostatic tachycardia syndrome. The preparation of the subject is important. Recommended tests should evaluate an adequate number of relevant autonomic systems. The Mayo laboratory utilizes two test batteries, the autonomic reflex screen and the reflex sympathetic dystrophy (RSD) screen. The former comprises the quantitative sudomotor axon reflex test (QSART), orthostatic blood pressure (BP) and heart rate (HR) responses to tilt, HR response to deep breathing, the Valsalva ratio, and beat-to-beat BP responses to the Valsalva maneuver, tilt, and deep breathing. The RSD screen comprises the recording of skin temperature, resting sweat output, and QSART distributions bilaterally. PMID- 8458993 TI - Functional anatomy of the autonomic nervous system. AB - The autonomic nervous system (ANS) via its sympathetic and parasympathetic divisions influences the function of nearly all organ systems. Via autonomic reflexes, the ANS is responsible for maintaining homeostasis of the internal environment. This is achieved by a rather complex integration of autonomic sensory information, somatic sensory information, and descending influences from higher central nervous system centers. PMID- 8458994 TI - New investigations of autonomic nervous system function. AB - Sensitive noninvasive techniques are available for beat-to-beat measurement of heart rate, blood pressure, and stroke volume. These allow for the assessment of the dynamic response capacity of the autonomic nervous system to stimuli that perturb baseline activity. In this review, the accuracy of volume clamp photoplethysmography for the measurement of finger arterial pressure and impedance cardiography for the measurement of cardiac output is critically evaluated. The utility of spectral analysis of blood pressure and heart rate for the routine assessment of autonomic function is discussed. It is suggested that these techniques will afford valuable information concerning central autonomic regulatory mechanisms and their dysfunction. PMID- 8458995 TI - Central autonomic disorders. AB - Central autonomic dysfunctions can be due to primary (degenerative) or secondary disorders. Autonomic failure (AF) may be a major manifestation of multiple system atrophy (MSA) and idiopathic Parkinson's disease (IPD). In both MSA and IPD, AF is almost invariably associated with neuronal loss in the intermediolateral cell columns. Dysautonomia in MSA is early, severe, and progressive, including marked orthostatic hypotension and urinary incontinence and is complicated by respiratory disturbances, such as laryngeal stridor and sleep apnea. MSA/AF can be differentiated from primary (or pure) autonomic failure (PAF) without central nervous system involvement. PAF is mainly a disorder of the postganglionic neurons. In contrast to PAF, MSA/AF has preserved basal sympathetic activity, decreased cerebrospinal fluid (CSF) neurotransmitter markers, impaired vasopressin response to hypotension, and impaired adrenocorticotrophic hormone/beta endorphin response to hypoglycemia. AF in IPD is generally less severe than in MSA. Poor response to L-Dopa, abnormal urethral sphincter electromyography, and CSF markers may distinguish MSA from IPD. Secondary autonomic disorders may result from traumatic, vascular, inflammatory, demyelinating, or neoplastic lesions involving corticolimbic, hypothalamic, brainstem, or spinal autonomic network. These disorders can cause AF or autonomic hyperactivity, such as arrhythmia, hypertension, and hyperthermia. However, many disorders may only produce subclinical abnormalities. PMID- 8458996 TI - The treatment of autonomic dysfunction. AB - Autonomic dysfunction is responsible for much of the morbidity associated with frequently encountered neurological disorders, such as Parkinson's disease, multiple sclerosis, cerebrovascular disease, and peripheral neuropathies, as well as with the rarer primary autonomic nervous system degenerations. We review the treatment of those aspects of autonomic dysfunction that often present to the neurologist, including orthostatic hypotension, urinary incontinence and retention, and bowel dysmotility syndromes. Pathophysiology is discussed in each instance as it relates to a rational approach to therapy. For management of orthostatic hypotension, we review the use of mineralocorticoids, direct and indirect sympathomimetic agents, other pressors, dopamine-blocking agents, vasopressin receptor agonists, and others. Treatment of urinary incontinence and retention is addressed, with attention to drugs that modulate bladder contractility and bladder outlet resistance. Therapies for bowel dysmotility syndromes (such as gastroparesis, diarrhea, and fecal incontinence) are described, including bulk agents, laxatives, prokinetic agents, and antidiarrheal drugs. PMID- 8458997 TI - EEG and clinical neurophysiology at Johns Hopkins medical institutions: roots and development. PMID- 8458998 TI - Intracerebral recordings: organization of the human epileptogenic region. AB - Intracranial recordings from patients with medically refractory partial epilepsy have demonstrated that the concept of a discrete epileptic focus, as derived from experiments with animals, does not exist in this human condition. Furthermore, an EEG spike focus, as defined by electroencephalographers, does not faithfully identify the site of ictal onset. Rather, the boundaries of an epileptogenic region, which is necessary and sufficient for generation of habitual spontaneous seizures, must be approximated by knowledge of the spatial distribution of interictal spike discharges, and ictal onset, as well as the location of an epileptogenic lesion demonstrated by structural imaging, and the location and extent of nonepileptic focal functional deficits. Delineation of an epileptogenic region is confounded by the fact that epileptically and nonepileptically abnormal brain tissue also exists beyond this area and may even involve the contralateral hemisphere. Investigations of epileptic patients during the course of surgical treatment have led to an improved understanding of the persistent neuronal disturbances that predispose to the generation of spontaneous seizures, as well as disturbances in adjacent and distant tissues that receive ictal propagation and demonstrate interictal epileptiform and nonepileptiform abnormalities. The results of such studies will greatly enhance our ability to interpret scalp recorded EEG transients and to devise better, noninvasive, diagnostic tools to accurately define the epileptogenic region. PMID- 8458999 TI - The neurophysiological basis of epileptiform magnetic fields and localization of neocortical sources. AB - In this review, we present animal studies that evaluate the appropriateness of the dipole model as a physical representation of neocortical sources produced by evoked and spontaneous epileptiform activity in neocortex. Three-dimensional electrical measurements of cellular currents in rat sensory neocortex are compared to associated extracranial magnetic fields. Comparisons are performed for the direct cortical response evoked by electrical stimulation of the cortical surface, and for evoked and spontaneous interictal and ictal discharge of the penicillin focus in the same animal preparation. These data support the hypothesis that evoked and epileptiform magnetic fields result from intradendritic currents oriented perpendicular to the cortical surface. Furthermore, magnetic fields can be detected from epileptic foci smaller than 3 x 3 mm2. Results from animal studies are then used as an empirical foundation for physical models with which to interpret noninvasive neuromagnetic recordings of epileptic discharge in human focal seizure disorders. Examples are presented in which the spatial and temporal distribution of extracranial magnetic fields produced by interictal events in humans may be adequately represented by multiple dipolar sources. PMID- 8459000 TI - Congenital muscular torticollis: sequela of intrauterine or perinatal compartment syndrome. AB - The etiology of congenital muscular torticollis remains a mystery despite intensive investigation. Magnetic resonance imaging (MRI) scans of 10 infants with this condition showed signals in the sternocleidomastoid muscle similar to those observed in the forearm and leg after compartment syndrome. Cadaver dissections and injection studies defined the sternocleidomastoid muscle compartment. Injection studies and pressure measurements performed at the time of bipolar release in three patients with congenital muscular torticollis confirmed the existence of this compartment in vivo. Clinical review of 48 children with congenital muscular torticollis showed a relation between birth position and the side affected by the contracture. Because of the association of congenital muscular torticollis with other intrauterine positioning disorders, we postulate that head positioning in utero can selectively injure the sternocleidomastoid muscle, leading to development of a compartment syndrome. Congenital muscular torticollis may represent the sequela of an intrauterine or perinatal compartment syndrome. PMID- 8459001 TI - Metastatic vertebral disease in children. AB - We retrospectively reviewed 19 children with osseous vertebral metastases. The average age was 10.9 years at diagnosis of the primary tumor and 11.2 years at diagnosis of metastasis. The location of the multiple metastases was cervical (three), thoracic (14), and lumbar (10). Treatment consisted of chemotherapy (19), radiation therapy (12), and operation (seven). Ten children died at an average of 13 months after diagnosis of the primary tumor; nine are alive at an average of 72 months after diagnosis. All four children treated with chemotherapy, spinal radiation, and laminectomy, and who survived > 2 months, developed deformity. In this particular situation, we encourage consideration of spinal stabilization when it is appropriately coordinated with radiation and chemotherapy. PMID- 8459002 TI - Long-term follow-up of patients with avascular necrosis after treatment of slipped capital femoral epiphysis. AB - A retrospective review of 264 patients treated for slipped capital femoral epiphysis (SCFE) identified 36 who developed avascular necrosis (AVN). Twenty-two patients (24 hips) were evaluated at an average follow-up of 31 years. Nine have undergone reconstructive surgery: four during adolescence and five during adulthood. The remaining 13 patients (15 hips) have had no further operations, but all show degenerative changes on current roentgenograms. The natural history appears to be that of gradual degenerative changes for which reconstructive surgery most often can be delayed until adulthood. PMID- 8459003 TI - Bone endoscopy: direct visual confirmation of cannulated screw placement in slipped capital femoral epiphysis. AB - Intraosseous endoscopic examination of the femoral neck and head was performed during the course of percutaneous screw fixation in 12 patients with slipped capital femoral epiphysis (SCFE). Visualization was satisfactory in 13 hips of these patients. We were able to distinguish trabecular bone and physeal cartilage endoscopically. Evidence of articular penetration was documented endoscopically in two patients. One patient had been referred for persistent hip pain and chondrolysis 6 months after screw insertion. Chronic joint penetration was observed endoscopically at the time of revision operation. In the second patient, transient pin penetration was visualized during cannulated screw fixation of a severe slip. PMID- 8459004 TI - Observations on symptomatic medial malleolar ossification centers. AB - We report 11 cases of symptomatic medial malleolar ossification centers (MMOC). Symptoms in six of the 10 patients responded to diminished athletic activity. Four patients required short-leg walking casts, and two of these patients required repeat casting for symptom recurrence. Two groups of bilateral, three view ankle roentgenograms of asymptomatic patients were reviewed to determine the incidence of MMOC. Group 1 (age 6 years 1 month to 12 years 11 months) had a 20% incidence, and group 2 (age 13 years 1 month to 17 years 11 months) had a 4% incidence. Symptoms may occur at these roentgenographic variants, and diminished activity, either volition or enforced by walking casts, produced resolution of symptoms in all patients. PMID- 8459005 TI - Normative ground reaction force data for able-bodied and below-knee-amputee children during walking. AB - We determined normative ground reaction force data for able-bodied (AB) and below knee-amputee (BKA) children during walking. Twenty-two BKA and 225 able-bodied children walked over two adjacent force platforms. Average normalized force-time curves were determined for legs of the children for subjective comparisons, and discrete variables were determined for statistical comparisons. No significant differences existed between (a) right and left legs, (b) gender, and (c) age for the AB children. BKA children had an asymmetrical gait pattern with a dominant role of the nonprosthetic limb. This dominant role was related to a greater rate of loading, magnitude of loading, impulse, and time of loading as compared with prosthetic limbs and with the limbs of AB children. PMID- 8459006 TI - Effects of selective dorsal rhizotomy on gait in children with cerebral palsy. AB - We wished to examine the effects of selective dorsal rhizotomy (SDR) on the gait patterns of children with cerebral palsy (CP). Nineteen ambulatory children underwent preoperative and 1-year postoperative gait analyses that included clinical assessment of joint range of motion (ROM) and muscle tone, three dimensional motion analysis, and dynamic electromyography (EMG). The children were divided into two groups: independent ambulators (n = 11) and dependent ambulators (requiring a walking aid) (n = 8). Improvements in joint passive ROM and a reduction in lower extremity spasticity were noted. In both groups, positive pre- to postoperative improvements were noted in sagittal plane hip, knee, and ankle motion and there was a greater incidence of a plantar-grade foot position in stance. There was no change in the coronal plane motion of the pelvis and hip. A mean increase in anterior pelvic tilt for the independent ambulators was the only major negative change observed in this study. We conclude that SDR improves specific gait parameters in children with CP. PMID- 8459007 TI - Management of valgus hindfoot deformity in pediatric cerebral palsy patients by medial displacement osteotomy. AB - To determine the clinical indications and efficacy of medial displacement osteotomy of the calcaneus in management of hindfoot valgus, we evaluated 18 feet (ten patients) prospectively. Average follow-up was 42 months; minimum follow-up was 24 months. The osteotomy was performed parallel to the subtalar joint through a lateral incision; the distal fragment was displaced > or = 50% and transfixed with two parallel pins for approximately 4 weeks. Analysis of hindfoot stability, foot position, and extremity function yielded excellent (n = 17) or fair (n = 1) results. Varus overcorrection in the "fair" foot required a closing wedge osteotomy. PMID- 8459008 TI - Recurrence after Achilles tendon lengthening in cerebral palsy. AB - We performed a retrospective review of all hemiplegic and diplegic cerebral palsy (CP) patients who had tendo-Achillis lengthening by open Z-plasty between 1974 and 1985. Fifty-seven patients with 77 heelcord lengthening were followed approximately 10 years. Our postoperative regimen did not routinely include bracing and physiotherapy, but our recurrence rates of 18 and 41% for diplegic and hemiplegic patients, respectively, are comparable to those reported in the literature. Children aged > or = 6 years at initial operation did not have recurrence. Diplegic patients who were operated on before age 4 years or patients who had longitudinal incisions had statistically significantly higher recurrence rates. PMID- 8459009 TI - Diminished knee flexion after hamstring surgery in cerebral palsy patients: prevalence and severity. AB - A review of pre- and postoperative prone knee flexion (PKF) data after isolated hamstring tenotomy for 52 patients with cerebral palsy (CP) at an average follow up of 3 years 4 months showed the frequency of diminished knee flexion to be 71%. Twenty-three percent of the knees actually had improved flexion, whereas 6% were unchanged. On the average, patients' flexion decreased 14.4 degrees from a preoperative PKF of 131.5 degrees to 117.1 degrees postoperatively (p < 0.0001). Only 11.5% of patients had PKF < 90 degrees at most recent follow-up, however; only 1.9% had PKF < 60 degrees. Thirteen percent of ambulators eventually required a rectus femoris transfer to correct "stiff-legged gait." PMID- 8459010 TI - Femoral torsion and neck-shaft angles in cerebral palsy. AB - Excessive femoral and coxa valga have been reported to be major contributors leading to hip dislocation in patients with cerebral palsy (CP). Femoral torsion angle (FT) and neck-shaft angle (NSA) were measured by the radiographic technique described by Rippstein and Muller in 157 patients with CP (289 hips). Factors associated with the degree of FT and NSA were evaluated. The researchers explored the correlation between the two angles and hip pathology. A large database of measurements was constructed. Our findings suggest that age and ambulatory status are the main factors correlated with FT and NSA. PMID- 8459011 TI - Comparison of lateral pillar classification and Catterall classification of Legg Calve-Perthes' disease. AB - To compare the predictive value of the Herring lateral pillar and the Catterall classifications of Legg-Calve-Perthes' disease, 71 hips with radiographic follow up to maturity were reviewed. The Herring classification was a significantly better predictor of Stulberg outcome than the Catterall classification. Three independent observers classified early fragmentation stage films by both Herring and Catterall classifications. The interobserver reliability of the Herring classification was significantly better than the reliability of the Catterall measure. PMID- 8459013 TI - Six generations of a family with multiple limb deficiencies. AB - Ectrodactyly, with or without other limb reduction defects, is a rare congenital anomaly. The pattern of inheritance is usually autosomal dominant, but with variable morphology. We report six generations of a family with this anomaly, with a progressive increase in severity and extent of involvement. Implications of genetic counseling are discussed. PMID- 8459012 TI - Fibular dimelia with deficiency of the tibia. AB - Longitudinal deficiency of the tibia associated with fibular dimelia is a very rare condition. We report our experience with six patients and outline management of this anomaly. Knee disarticulation is advised in cases with an associated normal femur, and femorofibular fusion is advised in cases of associated ipsilateral proximal focal femoral deficiency (PFFD) or congenital short femur. Fibulocalcaneal fusion and Boyd type amputation provide good end-bearing stumps. PMID- 8459014 TI - Pelvic osteotomy for bladder exstrophy. AB - Twenty-five patients with bladder exstrophy underwent pelvic osteotomy at or before initial bladder closure and anterior abdominal repair. Ten patients underwent bilateral iliac osteotomies before 1977. An alternative procedure consisting of bilateral superior pubic ramotomies has been used in 15 patients since 1977. In all patients, successful tension-free closure of the abdomen was achieved. Long-term follow-up of these two groups of patients shows no difference in the degree of pubic diastasis, which was asymptomatic. Posterior iliac osteotomy requires two additional incisions, longer operative time, and postoperative immobilization. We therefore recommend bilateral superior pubic ramotomy as an alternative procedure in initial reconstruction of the anterior abdomen in patients with bladder exstrophy. PMID- 8459015 TI - Effect of chemotherapy on human growth plate. AB - Histologic specimens of the distal femoral growth plates of 10 patients treated surgically for osteosarcoma were examined retrospectively. Eight of the patients received preoperative chemotherapy. None of the specimens showed complete growth arrest. The gross thickness of the plates was preserved. Columnar arrangement of the cells was minimally disrupted. The number of proliferative cells in each column was decreased, and the number of hypertrophic cells, was increased slightly. The metaphysis showed longitudinal trabeculations with a high chondroid content. Growth arrest lines were evidenced by transverse trabeculations with a high osteoid content. Our findings provide histologic support for previous clinical studies. Absence of complete growth arrest and evidence of a resumption of growth are relevant in planning limb salvage procedures in patients receiving pre- and postoperative chemotherapy for skeletal malignancy. PMID- 8459016 TI - Osteomyelitis in sickle cell disease. AB - Records of the Sickle Cell Clinics of the South Carolina Children's Rehabilitative Services from 1977 to 1990 were analyzed for cases of osteomyelitis. Cases included in the study demonstrated either positive bone cultures or blood cultures with correlating radiographs. Seven hundred seventeen charts were reviewed, and 16 cases of osteomyelitis were identified in 15 patients. Thirteen cases were due to Salmonella sp., one was due to Proteus mirabilis, one to Escherichia coli, and one to Staphylococcus aureus. The annual incidence of osteomyelitis in our series was 0.36%. PMID- 8459017 TI - Fractures of the triquetrum in children. AB - Fractures of the triquetrum are a more common cause of posttraumatic wrist pain in children than is usually appreciated. These fractures are often very subtle "flake" avulsion or impingement fractures requiring good oblique radiographs for recognition. The incidence is probably much higher because many fractures go undiagnosed as a wrist "sprain" or type I epiphyseal injury of the distal radius and ulna. An outcome study of carpal injuries at the Children's Hospital of Eastern Ontario, a regional pediatric trauma center, disclosed 15 children who had sustained a triquetral fracture. Three were initially missed, and most were flake fractures. An average follow-up of 4 years showed only two patients with complaints of wrist stiffness and discomfort with hyperextension of the wrist. The increased ligamentous laxity of the wrist in children may actually predispose to triquetral injury by causing ulnar impingement of the triquetrum with ulnar deviation and extension of the wrist. Pain in a child's wrist just distal to the ulna, the "triquetral point," should arouse suspicion of a fracture of the triquetrum. PMID- 8459018 TI - Management of radial neck fractures in children: a retrospective analysis of one hundred patients. AB - One hundred patients with radial neck fractures treated at the Royal Liverpool Children's Hospital, Alder Hey, were analyzed. Excellent and good results were obtained consistently after closed manipulation. Open reduction was often followed by a fair or poor result. Operative correction should not be attempted unless the radial head is displaced > 5 mm or unless residual angulation is > 45 degrees. Transcapitellar K-wire fixation has serious complications. Avascular necrosis (AVN), radial head enlargement, and notching of the radial neck were the most common complications. PMID- 8459019 TI - Fractures of the olecranon in children: long-term follow-up. AB - Olecranon fractures are relatively uncommon in children, and most are nondisplaced or minimally displaced fractures that can be treated by closed methods. During a 30-year period, 44 olecranon fractures were treated. Of 41 fractures with adequate follow-up, 37 (90%) had satisfactory results. Of 30 undisplaced or minimally displaced (< 5 mm) fractures, 28 (93%) had satisfactory results. Seven of 9 (78%) displaced fractures had satisfactory results. The most common cause of unsatisfactory results was loss of motion, although this usually did not prevent good function. PMID- 8459020 TI - Femur fractures in institutionalized patients after hip spica immobilization. AB - The charts of 77 severely handicapped institutionalized children and young adults were retrospectively reviewed to assess the incidence of femur fractures. No fractures occurred in ambulatory patients. Four of 37 nonambulatory patients who did not have hip surgery (10.9%) had sustained a fracture at some time during their life. Six of 21 (29%) nonambulatory patients who were operated on for subluxed or dislocated hips sustained a femur fracture within 3 months after discontinuation of their spica casts. This risk factor should be taken into account when one considers operation in severely affected nonambulant spastic quadriplegic patients. PMID- 8459021 TI - Metaphyseal extensions of hypertrophied chondrocytes in abused infants indicate healing fractures. AB - We examined histologically 40 bones from 11 infants aged < 1 year who died with evidence of infant abuse. Twenty-three bones had fractures, and 15 of these contained conspicuous metaphyseal extensions of hypertrophied chondrocytes (EHC) which were highly associated with healing fracture sites. These data indicate that such lesions are common in fractures related to child abuse, are easily identified, and are indicative of healing fractures. The presence of this lesion has significant implications for those who assess skeletal injury in abused infants because the determination of infant abuse often relies on establishing a pattern of skeletal trauma. Quantitation of the growth rate of individual physes in this age group may eventually permit assessment of the minimum age of these skeletal injuries. PMID- 8459022 TI - Prevalence of late-onset tibia vara. AB - We wished to determine the prevalence of late-onset tibia vara in an at-risk population. From a group of 1,117 boys aged 13-19 years, we selected all those who weighed at least 210 pounds. The 140 boys (80 black, 60 white) who met this inclusion criterion were examined for varus alignment. Radiographs of the seven boys who screened positive showed that two boys had late-onset tibia vara. Both boys were black and weighed > 280 pounds. The prevalence of late-onset tibia vara in this obese adolescent black male population was 2.5% (two of 80 boys). Recently, the number of reported cases of late-onset tibia vara has increased dramatically probably owing to an increase in the prevalence of morbid obesity. PMID- 8459023 TI - Normal limits of knee angle in white children--genu varum and genu valgum. AB - Knee angle and intermalleolar (IM) or intercondylar (IC) distance were measured in 196 white children aged 6 months to 11 years to establish normal limits of tibiofemoral angle. Children were maximally bowlegged at age 6 months and progressed toward approximately neutral knee angles (0 degree) by age 18 months. Greatest mean knock knee of 8 degrees was observed at age 4 years, followed by a gradual decrease to a mean of < 6 degrees at 11 years. Normal children aged 2-11 years had knock knee up to 12 degrees and intermalleolar distance up to 8 cm; the existence of bowlegs after age 2 years was abnormal. PMID- 8459024 TI - Range of knee motion in normal neonates. AB - Fifty-seven normal neonates were examined at birth and at 3 and 6 months (to within 7 days). Range of knee motion and of hip flexion contracture were measured. Mean knee flexion contracture was 21.4 degrees at birth, reducing to 10.7 degrees at 3 months and 3.3 degrees at 6 months. Decreasing range of knee flexion was noted in the same period. The natural history of normal knee motion is important in interpreting findings in patients with neuromuscular disorders. PMID- 8459025 TI - Recurrent dislocation of the patella in Kabuki make-up syndrome. AB - Three patients with Kabuki make-up syndrome (KMS) who had recurrent dislocation of the patella are reported. In all, dislocation of the patella developed in adolescence, and they had generalized ligamentous laxity and dysplasia of the patellofemoral joints. In two of the three patients, surgical intervention was required; the operation was successful in one, but yielded poor results in the other. In the third patient, cardiac complications precluded operation. Orthopedists should be aware of this possible complication when treating patients with KMS. PMID- 8459026 TI - Children at high risk for congenital dislocation of the hip: late presentation. AB - Several studies of risk factors and screening for congenital dislocation of the hip (CDH) have been reported, but some children are diagnosed too late and poor prognosis can be expected even with selective screening programs. The frequency of risk factors in late CDH presentation is not known. PMID- 8459027 TI - Supracondylar elbow fractures. PMID- 8459028 TI - ACP Broadsheet no 136: February 1993. Detection and importance of anticardiolipin antibodies. PMID- 8459029 TI - Immunohistochemical characterisation of the costochondral junction in SIDS. AB - AIM: To characterise the distribution of major growth plate proteoglycans in a group of infants who died of SIDS. METHODS: Nine such infants and eight age matched controls were selected from the necropsy files at the Adelaide Children's Hospital. Sections of rib and adjacent costal cartilage were stained for chondroitin-4-sulphate, chondroitin-6-sulphate, and keratan sulphate with antibodies 2-B-6, 3-B-3, and 5-D-4, respectively, using standard techniques. RESULTS: The distribution of proteoglycans within the extracellular matrix of the costochondral junction in the group of SIDS infants was identical with that found in control infants. CONCLUSION: Any changes present in the growth plate in cases of SIDS are most likely caused by secondary phenomena. PMID- 8459030 TI - Medullary carcinoma of the thyroid with carcinoid-like features. AB - AIMS: To show that medullary carcinomas of the thyroid are morphologically indistinguishable from gut carcinoids: the value of histochemistry in their identification and differential diagnosis from metastatic carcinoid tumours to the thyroid and some follicular cell neoplasms. METHODS: 15 thyroid medullary carcinomas with features of gut carcinoids were histochemically studied for the presence of argyrophil and argentaffin granules, and calcitonin, thyroglobulin, and serotonin immunoreaction. RESULTS: Histological features of midgut (classic) carcinoids were observed in two tumours, foregut carcinoids in 12, and hindgut carcinoids in one. All tumours showed, to a greater or lesser extent, a calcitonin immunoreaction and argyrophilia. These markers were present only in a small area showing a classic pattern of thyroid medullary carcinoma in the hindgut carcinoid-like neoplasm. Argentaffin granules and serotonin immunostaining occurred in occasional cells from four foregut carcinoid-like tumours. Thyroglobulin was not expressed in all cases and amyloid stroma was expressed in three. CONCLUSIONS: In some cases a diagnosis of metastatic carcinoid tumour to the thyroid can be considered only after ruling out clinically and histochemically medullary carcinoma of the thyroid. Immunolocalisation techniques are also essential for the differentiation between medullary carcinoma and thyroid follicular cell neoplasms that resemble carcinoid tumours. It is proposed that this tumour variant to be incorporated into current classifications as another histological subtype of C cell carcinoma. PMID- 8459031 TI - Importance of apoptosis in the histopathology of drug related lesions in the large intestine. AB - AIM: To investigate the possibility that the incidence of apoptotic bodies in the cryptal epithelium might help to identify colonic lesions due to drugs, especially non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: The apoptotic count (AC) the number of apoptotic bodies per 100 crypts was calculated in a series of colorectal biopsy specimens, stained with haematoxylin and eosin from patients with (a) known or suspected drug induced colitis and (b) inflammatory bowel disease before or after treatment with salazopyrine or corticosteroids. These specimens were compared with normal biopsy specimens from a control group of comparable age and sex distribution. RESULTS: Under normal conditions apoptotic bodies were seldom seen at all and the mean apoptotic count was less than 1.0. In untreated inflammatory bowel disease the mean apoptotic count was marginally increased (2.4), but when there was a partial response to drug treatment the apoptotic count rose to 13.1 (p 0.003). In colonic lesions directly attributable to drugs the apoptotic count was always increased, reaching its highest level (106) with 5-fluorouracil. In colitis related to NSAIDs apoptoses were associated with inflammation, most notably an increase in lymphocytes in both lamina propria and epithelium. CONCLUSION: The presence of crypt apoptoses in substantial numbers (with an apoptotic count in excess of 5) should always raise the possibility of drug effect. The mechanisms involved are not clear but with NSAIDs the changes might well be immunologically mediated. PMID- 8459032 TI - Monotypic plasma cells in labial salivary glands of patients with Sjogren's syndrome: prognosticator for systemic lymphoproliferative disease. AB - AIMS: To determine the prevalence of plasma cell monotypia in labial salivary gland tissue of patients with and without Sjogren's syndrome, and to evaluate its relation to the development of systemic monoclonal lymphoproliferative disorders. METHODS: A quantitative immunohistological study was performed on labial salivary gland tissue of 45 patients with Sjogren's syndrome, 18 with rheumatoid arthritis without Sjogren's syndrome, and 80 healthy controls. In none of the patients with Sjogren's syndrome was there evidence of systemic monoclonal lymphoproliferative disease at the time of biopsy. RESULTS: Monotypic plasma cell populations, defined by a kappa:lambda ratio of > or = 3, were only observed in older patients (above 43 years) with Sjogren's syndrome. In almost all these patients monotypic plasma cell populations were present in multiple labial salivary gland tissues and the IgM/kappa monotypia was observed most frequently. The prevalence of monotypic plasma cell populations in the group with Sjogren's syndrome was 22% (10/45) and there was no significant predilection for primary Sjogren's syndrome. Of special clinical interest was the observation that progression to systemic monoclonal lymphoproliferative disease had occurred exclusively in this subgroup of patients with Sjogren's syndrome, with a prevalence of 30% (3/10). CONCLUSION: Quantitative immunohistological examination of labial salivary gland tissues provides pathologists with a simple method to select those patients with Sjogren's syndrome who have an increased relative risk at the time of biopsy to develop benign or malignant lymphoproliferative disorders. PMID- 8459033 TI - Comparison of flow and static image cytometry in the determination of ploidy. AB - AIMS: To compare the efficiency of flow cytometry and computed image cytometry; and to see if a reliable set of guidelines regarding interpretation of histograms could be drawn up. METHODS: The two methods were applied to a series of 111 formalin fixed renal cell carcinomas. Data generated by both methods were compared. RESULTS: The methods agreed in 85 cases. Hypodiploidy was detected by computed image cytometry in seven cases in which flow cytometry had shown only an aneuploid peak. Aneuploidy in seven in which the corresponding flow cytometry histogram was diploid. There was an overlap in the second peak proportions on flow cytometry histograms between those classed as diploid or tetraploid by computed image cytometry. In six cases the flow cytometry histograms had unacceptably high coefficients of variation and in all of these cases computed image cytometry demonstrated aneuploidy. CONCLUSIONS: Computed image cytometry is particularly useful for clarifying difficult areas in flow histograms- specifically, high coefficients of variation, high G2M phase, as well as possible near diploid aneuploidy and hypodiploidy. PMID- 8459034 TI - Quantitative and qualitative comparison of DNA amplification by PCR with immunofluorescence staining for diagnosis of Pneumocystis carinii pneumonia. AB - AIM: To compare the results of DNA amplification by the polymerase chain reaction (PCR) with immunofluorescence staining for detecting Pneumocystis carinii in bronchoalveolar lavage specimens taken from symptomatic HIV seropositive patients with suspected P carinii pneumonia (PCP). METHODS: Bronchoalveolar lavage specimens were obtained from 28 symptomatic HIV seropositive patients. Specimens were examined for P carinii using immunofluorescence, and by DNA amplification with PCR to obtain results on gel electrophoresis (gel) and a more sensitive Southern hybridisation (blot) technique. Specimens positive by immunofluorescence and gel electrophoresis were serially diluted to a 10(-6) concentration and each dilution strength tested for P carinii using PCR to compare quantitatively immunofluorescence with PCR. RESULTS: Of the 28 specimens analysed, 18 were negative for P carinii by both immunofluorescence and PCR, two were positive only by the blot technique of PCR, four were equivocally positive and four unequivocally positive by immunofluorescence. Three of the four equivocally positive patients tested by immunofluorescence were negative for P carinii by PCR, although one was positive by PCR (blot) technique. This patient had clinically confirmed PCP. Of the four unequivocally positive patients tested by immunofluorescence, three were gel and blot positive by PCR and had PCP clinically, but one was negative by both gel and blot techniques, although the patient certainly had PCP on clinical grounds. This patient had received nine days of treatment with high dose co-trimoxazole before bronchoalveolar lavage specimens were obtained. The three specimens positive by gel and blot techniques remained gel positive down to dilutions of between 10(-4) and 10(-6). CONCLUSIONS: PCR results may become negative soon after starting treatment for PCP. Specimens should therefore be taken before, or soon after, starting treatment. PCR seems to be between 10(4) and 10(6) times more sensitive than immunofluorescence. PMID- 8459035 TI - New phenotypic typing scheme for group B streptococci. AB - AIMS: To develop a new typing system for group B streptococci based on 35S methionine-labelled protein profiles of bacterial proteins. METHODS: 377 clinical isolates of group B streptococci were examined by incorporation of 35S-methionine into bacterial proteins under strict anaerobic conditions. After sodium dodecylsulphate-polyacrylamide gel electrophoresis, autoradiography was performed. The patterns produced were visually analysed and categorised into clusters of organisms based on the pattern of band production between 32-46 kilodaltons. RESULTS: 294 of the typed strains classified into seven different groups designated a-g. 32 strains failed to incorporate 35S-methionine sufficiently to be grouped and 11 strains did not fall into one of the seven identified groups. Typability, reproducibility, and discrimination of the system was evident. CONCLUSIONS: This typing system may help to distinguish between colonising and invasive strains of the organism. PMID- 8459036 TI - Prognostic value of epidermal growth factor receptor expression in cervical carcinoma. AB - AIMS: To investigate the pattern of epidermal growth factor receptor expression and its prognostic value in the three main types of cervical carcinoma. METHODS: 62 cases of stage IB/IIA cervical carcinoma, all with a minimum of five years of follow up, were studied. Representative sections were stained for mucin to permit accurate tumour typing and a standard avidin-biotin immunoperoxidase technique using the polyclonal antibody 12E was used to demonstrate the presence of epidermal growth factor receptor. RESULTS: A proportion of all three tumour types expressed epidermal growth factor receptor, it being most common in squamous cell carcinomas (50%). Overall, there was a correlation between epidermal growth factor expression and mortality. This was particularly obvious in the absence of lymph node metastases. When the individual tumour types were considered this association with prognosis was not demonstrable for squamous cell carcinomas or adenocarcinomas but was a very prominent feature of adenosquamous carcinomas. CONCLUSIONS: Immunohistochemical demonstration of epidermal growth factor receptor expression may be useful in identifying those patients with a poor prognosis, particularly those with adenosquamous carcinomas which have not metastasised to the regional lymph nodes. PMID- 8459037 TI - Proliferative activity of urothelial neoplasms: comparison of BrdU incorporation, Ki67 expression, and nucleolar organiser regions. AB - AIMS: To evaluate the proliferative activity of urothelial neoplasms, compare it with that of the normal urinary tract epithelium, and determine its relation to morphological grade and presence of invasion. METHODS: Multiple biopsy specimens from 53 individuals--eight normal controls, five patients with severe urothelial atypia, and 40 with transitional cell carcinomas (TCCs)--were studied using in vitro bromodeoxyuridine (BrdU) incorporation, Ki67 antigen expression, and quantitation of the nucleolar organiser regions (NORs). RESULTS: The percentage of nuclei labelled by BrdU (BrdU index) correlated well with the percentage of nuclei expressing the Ki67 antigen (Ki67 index). These proliferation indices were very low (less than 0.1% in 60% of samples) in the urothelium of normal controls and the morphologically unremarkable epithelium of patients with TCCs. Non invasive TCCs had increased proliferation (BrdU index 6.32 (SD 0.8)%, Ki67 index 5.04 (0.6)% but lagged behind the invasive tumours (BrdU 20.9 (3.2)%, Ki67 18.6 (2.8)%). The average NOR count was 1.57 (0.03) in morphological normal epithelium, which increased progressively with grade in non-invasive TCCs, but varied greatly in invasive tumours and did not correlate with the proliferation indices. The spectrum of values for both proliferation indices and NORs was particularly wide in grade 2 TCCs. Severe atypias without exophytic growth had an increase in BrdU and Ki67 indices comparable with that found in grade 3-4 invasive TCCs; these also had the highest NORs per nucleus. CONCLUSIONS: The growth potential of urothelial neoplasms is an important indicator of their aggressive course. In particular, growth indices over 10% are strongly associated with the presence of invasion. Papillary grade 2 TCCs show heterogeneity in their growth characteristics which may relate to their diverse clinical course. The mitotic count underestimates the growth potential of papillary TCCs and the addition of proliferation indices such as BrdU incorporation or the Ki67 index may enhance the prognostic accuracy of conventional morphological grading. PMID- 8459038 TI - p53 expression in dyskeratosis congenita: a marker for oral premalignancy? AB - As p53 expression has been associated with malignant disease its presence was assessed in biopsy specimens from dorsal lingual hyperkeratosis, taken over a five year period. p53 expression, using CM1, was assessed using a standard immunoperoxidase technique. p53 was not identified in the first biopsy specimen in 1986 but was identified in all subsequent ones. Only in the latest biopsy specimen was there evidence for dysplasia in haematoxylin and eosin stained sections. It is suggested that p53 expression may be a reliable marker for predicting premalignant change in keratoses occurring in dyskeratosis congenita. PMID- 8459039 TI - Demonstration of mRNA using digoxigenin labelled oligonucleotide probes for in situ hybridisation in formamide free conditions. AB - The value of formamide for use in in situ hybridisation (ISH) for the detection of mRNA, using either single or multi probe cocktails of digoxigenin labelled oligoprobes, was investigated. Three peptides with cell specific localisation in three separate tissues--calcitonin in the thyroid, epidermal growth factor (EGF) in the submaxillary gland, and insulin in the pancreas were studied. In each case localisation was confined to the appropriate cell type, but in the presence of formamide higher concentrations of probe and a longer development time were required. The abolition of formamide from the protocol for ISH makes the technique safer, cheaper, faster and more suitable for routine diagnostic use. PMID- 8459040 TI - Lymph node disease with lymphocytic abnormal chromatin clumping in a myelodysplastic/myeloproliferative syndrome. AB - A case of abnormal chromatin clumping (ACC) which arose during the course of a myelodysplastic/myeloproliferative syndrome is described in a 61 year old woman who died of haemorrhage 43 months after diagnosis. Mature granulocytes exhibited the same nuclear abnormality described in other patients reported. Unusually, she presented with advanced splenomegaly and lymphadenopathy. This case was the third example of ACC in lymphocytes, the first with clinically confirmed lymphadenopathy. Diagnosis of this subset can be based on: older age; short duration of symptoms; no specific karyotypic damage; non-rearranged bcr; proliferative growth pattern in vitro; numerous circulating myelocytes; profound thrombocytopenia. PMID- 8459041 TI - Neutropenic enterocolitis associated with Clostridium tertium. AB - A 15 year old boy being treated for relapsed acute lymphoblastic leukaemia developed severe diarrhoea and abdominal pain which worsened despite empirical antibiotic treatment. A right hemicolectomy was performed. The caecum and ascending colon showed changes typical of neutropenic enterocolitis. Clostridium tertium was isolated from faeces, blood cultures, and from the resected gut wall, with no evidence of other organisms capable of causing such a condition. As far as is known, this is the first reported case in which neutropenic enterocolitis has been associated with well documented C tertium infection, an organism previously described as a cause of bacteraemia in neutropenic patients. PMID- 8459042 TI - Mixed adenocarcinoma/carcinoid tumour of large bowel in a patient with Crohn's disease. AB - A 50 year old woman with a 20 year history of Crohn's disease underwent laparotomy which revealed extensive disease in the small and large bowel, and this was resected. Gross examination of the resected bowel showed features of Crohn's disease as well as a polypoid tumour in the caecum. Histopathological examination of the tumour showed it to be an infiltrating mixed adenocarcinoma/carcinoid tumour arising in a tubulovillous adenoma. Random sampling of the rest of the bowel affected by Crohn's disease also showed a focus of dysplasia and adenomatous change. It is suggested that Crohn's disease may have played a part in the pathogenesis of the tumour. PMID- 8459043 TI - Modification of simple and specific test for measuring lipid peroxides in plasma. PMID- 8459044 TI - Parathyroid hormone related protein (PTHrP) in hypercalcaemia of lymphoproliferative disease. PMID- 8459045 TI - AgNOR quantification in tumour pathology: what is actually evaluated? PMID- 8459046 TI - Method for grading breast cancer. PMID- 8459047 TI - Immunophenotype of multinucleated cells in giant cell lesions. PMID- 8459048 TI - The British Society for Haematology Guidelines on the use and monitoring of heparin 1992: second revision. BCSH Haemostasis and Thrombosis Task Force. PMID- 8459049 TI - Neurofilament mRNA is reduced in Parkinson's disease substantia nigra pars compacta neurons. AB - Lewy bodies are filamentous neuronal inclusions characteristic of Parkinson's disease, and neurofilament triplet proteins are the major components of the filaments in Lewy bodies. Since the neurofilament proteins found in Lewy bodies are abnormally phosphorylated and partially degraded, the formation of Lewy bodies may be due to the defective metabolism of these proteins, and this could lead to impairments in the structure and function of neurofilament rich neuronal processes (i.e., large caliber axons). To gain further insights into the metabolism of neurofilaments in Parkinson's disease, we evaluated neurofilament mRNA levels by semi-quantitative in situ hybridization histochemistry in postmortem tissues from Parkinson's disease and control subjects. Substantia nigra pars compacta neurons were examined with digoxigenin-UTP labeled cRNA probes to the heavy and light neurofilament mRNAs. The relative abundance of these mRNAs was measured by videodensitometric image analysis of chromogenic reaction product. Using this approach, we demonstrated that the levels of both heavy and light neurofilament mRNAs were reduced in Parkinson's disease substantia nigra pars compacta neurons. Additionally, the levels of heavy neurofilament mRNA were lowest in Lewy body containing neurons in the Parkinson's disease cases. These results suggest that the formation of neurofilament-rich Lewy bodies in substantia nigra pars compacta neurons is associated with reduced levels of the heavy and light neurofilament mRNAs in Parkinson's disease. Thus, it is possible that the accumulation of abnormal neurofilament proteins in Lewy bodies and diminished neurofilament mRNAs contribute to the degeneration of substantia nigra pars compacta neurons in Parkinson's disease. PMID- 8459050 TI - Morphology of the vasopressin-like immunoreactive (VPLI) neurons in many species of grasshopper. AB - It has previously been shown that the pair of vasopressin-like immunoreactive (VPLI) neurons of the locust, Locusta migratoria, have cell bodies on the ventral midline of the suboesophageal ganglion and extensive arborisations in all ganglia of the central nervous system. In the present study, we have stained vasopressin like immunoreactive neurons in 16 additional species of grasshopper, and consistently find this pair of extensive neurons: we assume these to be interspecies homologues. However, the anatomy of these neurons falls into two morphological types: the first, typified by Schistocerca gregaria, has most of its processes distributed in dorsal and lateral neuropil of all ganglia; the second, typified by Locusta migratoria, is equally extensive in its arborisation, but the distribution of branches is shifted peripherally into the optic lobes and the proximal portions of peripheral nerves. It has been suggested that the peripheral fibres in Locusta migratoria are neurohaemal organs for the release of a vasopressin-like diuretic peptide. Our sample of 17 Acridoid species has deliberately selected animals from very different habitats, but our extensive survey of VPLI anatomy shows that peripheral fibres are only present in species from the subfamily Oedipodinae (of which Locusta migratoria is a member) and that no peripheral fibres are present in any of the species from the 4 other subfamilies of the Acridoidea that we have examined. The presence of peripheral fibres is therefore determined by phylogeny and not by habitat. The absence of peripheral VPLI fibres in most grasshopper species examined in this study probably means that the release of putative diuretic hormone from VPLI to control water homeostasis cannot be a conserved function of this ubiquitous neuron. In contrast, the extensive central arborisations and rare antigenicity, which are highly conserved features of the VPLI neuron in all those grasshoppers we have examined, suggests that any conserved role is more likely to be central. A central role for the VPLI neuron has yet to be determined. PMID- 8459051 TI - Plasticity of auditory cortex associated with sensorineural hearing loss in adult C57BL/6J mice. AB - The representation of frequency was mapped in the primary auditory cortex (AI) of C57BL/6J (C57) mice during young adulthood (1.5-2 months) when hearing is optimal, and at 3, 6, and 12 months of age, a period during which progressive, high frequency, sensorineural hearing loss occurs in this strain. Maps were also obtained from CBA/CaJ mice which retain good hearing as they age. In AI of young adult C57 mice and CBA mice, characteristic frequencies (CFs) of multiple-unit clusters were easily identified with extracellular recordings, and a general tonotopic organization was observed from dorsal (high frequency) to ventral and caudal (low frequency). In individual cases there appeared to be deviations from the above tonotopic organization, despite the fact that inbred mice are genetically invariant. As progressive loss of high frequency sensitivity ensued peripherally, a substantially increased representation of middle frequencies was observed in AI. There was no apparent change in the surface area of the auditory cortex despite the elimination of high frequencies, and virtually the entire auditory cortex became devoted to the middle frequencies (especially 10-13 kHz) for which sensitivity remained high. Similar age-related changes were not observed in normal-hearing CBA mice. These findings indicate that plasticity in the representation of frequency in AI is associated with high frequency hearing loss in C57 mice. PMID- 8459052 TI - Correlation between the receptive fields of locust interneurons, their dendritic morphology, and the central projections of mechanosensory neurons. AB - The relationships between the morphology and receptive fields of local and intersegmental interneurons that process mechanosensory information from a hindleg of the locust have been analysed. Sensory neurons from tactile hairs project to ventral areas of neuropil in the metathoracic ganglion where they form a 3-dimensional somatotopic map of a hindleg. By contrast, sensory neurons from a proprioceptor at the femoro-tibial joint (the femoral chordotonal organ) project to lateral and more intermediate areas of neuropil and have no branches in the most ventral regions of neuropil. Particular local and intersegmental interneurons respond to stimulation of specific arrays of hairs on a hindleg, or to movements of particular joints. Their receptive fields are defined, in part, by the patterns of excitatory, monosynaptic connections made by these afferents. Each interneuron has a characteristic receptive field and a characteristic morphology defined by its array of branches in the regions of neuropil containing the projections of the afferents that provide its monosynaptic inputs. Interneurons with inputs exclusively from tactile hairs have branches in the most ventral regions of neuropil, while those with exclusively proprioceptive inputs have branches only in more intermediate levels of neuropil. Interneurons with extensive receptive fields from tactile hairs also have extensive areas of branching within the ventral neuropil. Interneurons with receptive fields restricted to particular regions of the leg have branches restricted to the ventral region of neuropil containing the projections of afferents from that part of the leg. Thus, interneurons with inputs only from hairs on the tarsus have branches in the posterior region of neuropil corresponding to the projections of the tarsal afferents, while interneurons with receptive fields on the femur have branches in more anterior regions of neuropil corresponding to the projections of the femoral hair afferents. Interneurons with receptive fields on the tibia have branches in neuropil between the tarsal and femoral projections. PMID- 8459053 TI - Diminished hyperaemic response of the hepatic artery to portal venous occlusion (the buffer response) in Asian hybrid minipigs: a comparison of the response to that observed in dogs. AB - The hyperaemic response of the hepatic artery to portal vein occlusion (the buffer response) and the action of exogenous adenosine upon hepatic artery blood flow was studied in Asian hybrid minipigs as a potential alternative experimental model to that previously developed in dogs. Adenosine produced a dose-dependent hepatic artery vasodilatation, but of lesser extent than that observed in dogs. A greatly diminished buffer response was observed in the pigs compared to that seen in dogs, and could not be replicated consistently. The adenosine uptake inhibitor dipyridamole did not potentiate responses to adenosine or the buffer response. It is concluded that the minipig is an unsuitable alternative model for the study of the hepatic artery buffer response. PMID- 8459054 TI - High altitude tissue adaptation in Andean coots: capillarity, fibre area, fibre type and enzymatic activities of skeletal muscle. AB - Capillarity, fibre types, fibre area and enzyme activities of different skeletal muscles (pectoralis, extensor digitorum longus), tibialis anterior, plantaris and the myocardium) were compared in Andean coot (Fulica americana peruviana) native to high altitude (Junin, Peru, 4200 m) and the same species nesting at sea level. Numbers of capillaries per square millimeter were higher in all high-altitude muscles when compared with sea-level muscles (P < 0.0001). Moreover, values for capillaries per fibre and capillaries in contact with each fibre were higher in digitorum and tibialis high-altitude muscles. Muscle fibres were classified as Type I, Type IIA or Type IIB on the basis of their myofibrillar ATPase pH lability. Pectoralis muscle of high-altitude and sea-level coots presented only fibres of Type IIA. In contrast, all the leg muscles studied showed a mosaic pattern of the three fibre types. Fibre areas were determined using a Leitz Texture Analysis System. Significant differences in fibre area were observed (P < 0.01) between high-altitude and sea-level muscles. Mean muscle fibre diameters were also lower in the high-altitude group than in the sea-level group. The enzyme activities studied were hexokinase, lactate dehydrogenase, citrate synthase and 3-hydroxyacyl-CoA-dehydrogenase. The oxidative capacity, as reflected by citrate synthetase and hydroxyacyl-CoA-dehydrogenase activities, was greater for myocardial and pectoralis than for leg muscles. However, analysis of maximal enzyme activities showed that there were no significant differences between the glycolytic and oxidative enzyme activities of high-altitude and sea level coots.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8459055 TI - Evidence for a rebound coagulation phenomenon after cessation of a 4-hour infusion of a specific thrombin inhibitor in patients with unstable angina pectoris. AB - OBJECTIVES: In a Phase I clinical trial, we studied the antithrombotic and clinical effects of the synthetic competitive thrombin inhibitor, argatroban, in 43 patients with unstable angina pectoris. BACKGROUND: Thrombin has a pivotal role in platelet-mediated thrombosis associated with atheromatous plaque rupture in patients with an acute ischemic coronary syndrome. However, the efficacy of conventional heparin therapy to prevent ischemic events is limited and has been surpassed by that of specific thrombin inhibitors in experimental models of arterial thrombosis. METHODS: Intravenous infusion of the drug (0.5 to 5.0 micrograms/kg per min) for 4 h was monitored by sequential measurements of coagulation times and of indexes of thrombin activity in vivo followed by a 24-h clinical observation period. RESULTS: Significant dose-related increases in plasma drug concentrations and activated partial thromboplastin times (aPTT), but no bleeding time prolongation or spontaneous bleeding, was observed. Myocardial ischemia did not occur during therapy but, surprisingly, 9 of the 43 patients experienced an episode of unstable angina 5.8 +/- 2.6 h (mean +/- SD) after infusion. This early recurrent angina was correlated significantly with a higher argatroban dose and with greater prolongation of aPTT but not with other demographic, clinical, laboratory and angiographic characteristics. Pretreatment plasma concentrations of thrombin-antithrombin III complex and fibrinopeptide A were elevated two to three times above normal values. During infusion, thrombin antithrombin III complex levels remained unchanged, whereas a significant 2.3 fold decrease in fibrinopeptide A concentrations was observed. By contrast, 2 h after infusion, thrombin-antithrombin III complex concentrations increased 3.9 fold over baseline measurements together with return of fibrinopeptide A levels to values before treatment with argatroban. CONCLUSIONS: In patients with unstable angina, argatroban inhibits clotting (aPTT prolongation) and thrombin activity toward fibrinogen (fibrinopeptide A decrease), but in vivo thrombin (thrombin-antithrombin III complex) formation is not suppressed. However, cessation of infusion is associated with rebound thrombin (thrombin-antithrombin III complex) generation and with an early dose-related recurrence of unstable angina. Although the mechanism of this clinical and biochemical rebound phenomenon remains to be determined, its implication for the clinical use of specific thrombin inhibitors in the management of ischemic coronary syndromes may be significant. PMID- 8459056 TI - Thrombin inhibitors in unstable angina: rebound or continuation of angina after argatroban withdrawal? PMID- 8459057 TI - Effect of a standardized meal on the threshold of exercise-induced myocardial ischemia in patients with stable angina. AB - OBJECTIVES: This study was undertaken to determine the effect of a standardized meal on the ischemic threshold and exercise capacity in a series of 20 patients with stable angina, exercise-induced ischemia and reversible exercise-induced perfusion defects. BACKGROUND: It is generally accepted that exercise tolerance in patients with angina is reduced after a meal. However, studies that have addressed this phenomenon have yielded results that are contradictory and inconclusive. METHODS: Two exercise tests using the Bruce protocol with technetium-99m (99mTc)-sestamibi were performed on consecutive days in a randomized order. One test was performed in the fasting state and the other 30 min after a 1,000-calorie meal. RESULTS: In the postprandial state, exercise time to ischemia was reduced by 20% from 248 +/- 93 s to 197 +/- 87 s (p = 0.0007), time to angina by 15% from 340 +/- 82 s to 287 +/- 94 s (p = 0.002) and exercise tolerance by 9% from 376 +/- 65 s to 344 +/- 86 s (p = 0.002). Rate-pressure products at these exercise test end points were not significantly different in the fasting and postprandial tests, and the quantitative 99mTc-sestamibi ischemia score was unchanged. CONCLUSIONS: In patients with stable angina, a 1,000-calorie meal significantly reduced time to ischemia, time to angina and exercise tolerance because of a more rapid increase in myocardial oxygen demand with exercise. The extent and severity of exercise-induced ischemia were unchanged. PMID- 8459058 TI - Do false positive thallium-201 scans lead to unnecessary catheterization? Outcome of patients with perfusion defects on quantitative planar thallium-201 scintigraphy. AB - OBJECTIVES: We postulated that artifactually abnormal thallium-201 scans are well identified at the time of initial clinical interpretation by experienced readers and do not lead to unnecessary coronary angiography. BACKGROUND: Exercise thallium-201 scintigraphy employing quantitative imaging techniques has yielded sensitivity and specificity values of 80% to 90%. There are image artifacts, such as breast shadows, and variants of normal that, if not correctly identified, can lead to a high false positive rate for detection of coronary artery disease. METHODS: Data from 338 consecutive patients with one or more focal thallium-201 defects on quantitative planar images were reviewed. All patients had undergone symptom-limited exercise scintigraphy and were classified as having either artifactual or nonartifactual thallium-201 defects after review of clinical reports. RESULTS: Of the 265 patients with defects judged to be nonartifactual on clinical readings, 167 underwent coronary angiography, which demonstrated significant coronary artery disease (> or = 50% stenosis) in 161 (96%) and normal findings in 6. Four of the latter six had documented prior myocardial infarction. The remaining 73 patients (85% female) had thallium-201 defects deemed to be artifactual on clinical readings, chiefly as a result of breast (66%) and diaphragmatic (8%) attenuation or variants of normal (26%). Only 4 (5%) of the 73 patients underwent subsequent coronary angiography; none had coronary artery disease. One had aortic stenosis and two had variant angina. Follow-up (mean 20 +/- 2 months) of the 69 patients in this group who did not undergo coronary angiography revealed no deaths and one nonfatal non-Q wave myocardial infarction. CONCLUSIONS: Artifactual defects on quantitative planar thallium-201 scintigraphy are well recognized by experienced interpreters and do not result in a high false positive rate leading to unnecessary cardiac catheterization. The incidence of coronary artery disease is high in patients with thallium-201 defects judged to be nonartifactual, and many patients with perfusion defects and angiographically normal coronary arteries have organic heart disease. PMID- 8459059 TI - Factors affecting uniformity in interpretation of planar thallium-201 imaging in a multicenter trial. The Multicenter Study on Silent Myocardial Ischemia (MSSMI) Thallium-201 Investigators. AB - OBJECTIVES: This study was designed to assess factors affecting interobserver agreement in interpretation of planar thallium-201 stress imaging in the Multicenter Study on Silent Myocardial Ischemia (MSSMI). BACKGROUND: Five hundred fifty-six planar thallium-201 images were interpreted in 24 clinical centers and in a Radionuclide Core Laboratory. The trial's Coordinating and Data Center observed that the participating clinical centers interpreted a significantly greater number of thallium-201 stress studies as abnormal (i.e., myocardial ischemia or scar) than the Core Laboratory, and overall agreement was poor (kappa 0.27). METHODS: Agreement in image interpretation between clinical centers and the Radionuclide Core Laboratory was analyzed by kappa statistics. The reproducibility of the Core Laboratory results on 41 randomly selected test studies was excellent (kappa 0.77). In contrast, the reproducibility of interpretation in the clinical centers on their own studies was at best fair (kappa 0.45). It was hypothesized that the poor agreement and reproducibility in the clinical centers were caused by lack of standardization of image display and lack of objective criteria for image interpretation. To test the effect of standardization, 13 clinical investigators interpreted the same 41 test studies using 1) uniform image display, and 2) uniform quantification of images. RESULTS: The agreement in interpretation between clinical investigators and the Radionuclide Core Laboratory improved modestly with uniformity of image display (kappa 0.57) but improved markedly (kappa 0.66) with quantitative circumferential profile analysis. CONCLUSIONS: Lack of standardization in image display and lack of objective criteria for interpretation of thallium-201 images are responsible for suboptimal reproducibility and poor interlaboratory agreement in the interpretation of thallium-201 stress imaging. The adoption of a uniformly accepted method for computer quantification of myocardial perfusion images is crucial to improve agreement in interpretation. PMID- 8459060 TI - Effects of intravenous theophylline on exercise-induced myocardial ischemia. I. Impact on the ischemic threshold. AB - OBJECTIVES: Theophylline has been shown to delay the onset of myocardial ischemia and to prolong exercise duration. The present study was done to evaluate the mechanisms and actions of intravenous theophylline on the onset of ischemia and exercise duration. BACKGROUND: The ischemic threshold may be altered by the differential coronary vasodilation induced by endogenous adenosine. Theophylline is a competitive receptor antagonist of adenosine and may have a potential as an anti-ischemic medication. METHODS: A double-blind, placebo-controlled crossover trial using an infusion of intravenous theophylline (8.0 +/- 2.0 mg/liter) or placebo before exercise in 12 patients was done. Oxygen uptake, heart rate, blood pressure and heart rate-blood pressure product were determined at the onset of > or = 0.1-mV ST segment depression and angina pectoris, as well as at peak exercise. The extent of myocardial ischemia was evaluated by electrocardiographic criteria and quantitation of thallium-201 images at peak exercise. RESULTS: When compared with placebo, theophylline significantly delayed time to the onset of exercise-induced ischemia. Ischemia occurred at a higher heart rate-blood pressure product and oxygen uptake. Exercise duration was prolonged but was not associated with greater ischemia, as determined by oxygen uptake, ST segment depression, angina pectoris and size of thallium-201 defect. CONCLUSIONS: It is concluded that theophylline favorably alters myocardial ischemia not only by delaying its onset but also by enabling it to occur at a higher threshold without causing deleterious effects during exercise. The mechanism for the increased ischemic threshold may be through the inhibition of adenosine and the coronary steal phenomenon. PMID- 8459061 TI - Paradoxic hypotension during dobutamine stress echocardiography: clinical and diagnostic implications. AB - OBJECTIVES: The purpose of this study was to elucidate the prevalence, magnitude and clinical implications of a hypotensive response during dobutamine stress echocardiography. BACKGROUND: Dobutamine stress echocardiography is an accurate noninvasive method for detecting coronary artery disease. It has been associated with unexpected hypotension in a proportion of patients. Hypotension occurring during exercise testing has been associated with an increased prevalence of multivessel coronary artery disease and a poor prognosis. The clinical significance of hypotension when seen during dobutamine infusion for diagnostic testing is unknown. METHODS: Clinical characteristics, coronary artery anatomy (n = 41), ventricular function at rest and during dobutamine infusion and prognosis were evaluated in 115 patients experiencing hypotension during dobutamine stress echocardiography and compared with data in 59 nonhypotensive catheterized patients for comparison of coronary anatomy and in 239 nonhypotensive patients for prognostic purposes. RESULTS: Hypotension occurred in 115 (20%) of 568 consecutive patients studied with dobutamine stress echocardiography. It was gradual in 73 and precipitous in 42 patients. There were no statistical differences among the hypotensive groups and the index group in prevalence or severity of coronary disease or in prognosis during 15 months compared with findings in nonhypotensive patients. CONCLUSIONS: Hypotension occurs commonly during dobutamine stress echocardiography, and patients with dobutamine-induced hypotension constitute a heterogeneous group. Unlike hypotension occurring with exercise testing, dopamine-induced hypotension is not invariably associated with advanced coronary disease or an adverse prognosis. PMID- 8459062 TI - Exercise echocardiography for the evaluation of patients after nonsurgical coronary artery revascularization. AB - OBJECTIVES: The purpose of this study was to demonstrate the accuracy of stress echocardiography for detecting the progression of coronary artery disease after nonsurgical revascularization. BACKGROUND: The expanding role of nonsurgical coronary revascularization procedures mandates the development of sensitive noninvasive techniques for the detection of recurrent ischemia. METHODS: Bicycle stress echocardiography was performed in a series of 86 patients 6.5 +/- 1.3 months after a revascularization procedure. Seven patients were excluded from analysis because of poor echocardiographic image quality. RESULTS: Digital analysis achieved a sensitivity of 83% for the entire group and a specificity of 85% for stress echocardiographic detection of significant coronary artery disease. Sensitivity was greater in patients with (88%) than in those without (75%) prior myocardial infarction, but this difference did not reach statistical significance. Additional analysis using an increase in end-systolic volume index or a decrease in ejection fraction during stress as an additional marker for ischemia tended to enhance sensitivity (90% for the entire group and 93% for the subgroup with prior myocardial infarction). CONCLUSIONS: Stress echocardiography is a useful and sensitive method for the follow-up of patients undergoing nonsurgical revascularization procedures. The addition of volume determination to routine wall motion analysis may be helpful in patients with prior infarction who have scar tissue that may be difficult to distinguish from an adjacent exercise induced wall motion abnormality. PMID- 8459063 TI - Physical training improves skeletal muscle metabolism in patients with chronic heart failure. AB - OBJECTIVES: This study investigated the effects of physical training on skeletal muscle metabolism in patients with chronic heart failure. BACKGROUND: Skeletal muscle metabolic abnormalities in patients with chronic heart failure have been associated with exercise intolerance. Muscle deconditioning is a possible mechanism for the intrinsic skeletal muscle metabolic changes seen in chronic heart failure. METHODS: We used phosphorus-31 nuclear magnetic resonance spectroscopy to study muscle metabolism during exercise in 12 patients with stable ischemic chronic heart failure undergoing 8 weeks of home-based bicycle exercise training in a randomized crossover controlled trial. Changes in muscle pH and concentrations of phosphocreatine and adenosine diphosphate (ADP) were measured in phosphorus-31 spectra of calf muscle obtained at rest, throughout incremental work load plantar flexion until exhaustion and during recovery from exercise. Results were compared with those in 15 age-matched control subjects who performed a single study only. RESULTS: Before training, phosphocreatine depletion, muscle acidification and the increase in ADP during the 1st 4 min of plantar flexion exercise were all increased (p < 0.04) compared with values in control subjects. Training produced an increase (p < 0.002) in incremental plantar flexion exercise tolerance. After training, phosphocreatine depletion and the increase in ADP during exercise were reduced significantly (p < 0.003) at all matched submaximal work loads and at peak exercise, although there was no significant change in the response of muscle pH to exercise. After training, changes in ADP were not significantly different from those in control subjects, although phosphocreatine depletion was still greater (p < 0.05) in trained patients than in control subjects. The phosphocreatine recovery half-time was significantly (p < 0.05) shorter after training, although there was no significant change in the half-time of adenosine diphosphate recovery. In untrained subjects, the initial rate of phosphocreatine resynthesis after exercise (a measure of the rate of oxidative adenosine triphosphate [ATP] synthesis) and the inferred maximal rate of mitochondrial ATP synthesis were reduced compared with rates in control subjects (p < 0.003) and both were significantly increased (p < 0.05) by training, so that they were not significantly different from values in control subjects. CONCLUSIONS: The reduction in phosphocreatine depletion and in the increase in ADP during exercise, and the enhanced rate of phosphocreatine resynthesis in recovery (which is independent of muscle mass) indicate that a substantial correction of the impaired oxidative capacity of skeletal muscle in chronic heart failure can be achieved by exercise training. PMID- 8459064 TI - Reversed closure sequence of the mitral and tricuspid valves in congestive heart failure. AB - OBJECTIVES: The purpose of this study was to evaluate functional and hemodynamic factors that determine the mitral-tricuspid and aortic-pulmonary valve closure sequence in patients with dilated cardiomyopathy. BACKGROUND: The physiologic factors determining closure sequence of cardiac valves in various forms of heart disease have been found to be complex. Few data exist for dilated cardiomyopathy, particularly for differentiating the effects of a conduction delay versus changes in ventricular performance. METHODS: A group of 64 patients were compared with 36 control subjects. Timing of valve closure and electromechanical intervals were determined by combined M-mode echocardiography, phonocardiography and apexcardiography. Hemodynamic data from right heart catheterization were available in 46 patients. RESULTS: In all control subjects, the aortic valve closed before the pulmonary valve and the mitral valve closed before the tricuspid valve. In the study group, 30 patients (49%) had reversed aortic pulmonary valve closure and 27 (90%) of these had a left-sided conduction delay. There were 38 patients (60%) who had reversed mitral-tricuspid valve closure, but this was unrelated to the presence of a left-sided conduction delay. The presence of high ventricular filling pressures and poor systolic function was associated with delayed closure of both the mitral and the tricuspid valve. This caused the closure sequence to be related to the size of the difference between mean pulmonary artery wedge pressure and mean central venous pressure and also the magnitude of right ventricular dysfunction. Patients with a low wedge pressure (< 16 mm Hg) and a low central venous pressure (< 10 mm Hg) had a low prevalence of mitral-tricuspid valve closure reversal (30%). Those with a high wedge pressure (> 16 mm Hg) but a low central venous pressure had a high prevalence (86%) of reversal of mitral-tricuspid valve closure. Patients with high wedge and central venous pressures had a moderate prevalence (47%) of mitral-tricuspid valve closure reversal. Similar findings were observed for right ventricular dysfunction. If the right ventricle was normal or severely dysfunctional, a reversed closure sequence was less common (52% and 41%, respectively) than if moderate dysfunction was present (78%). CONCLUSIONS: Aortic-pulmonary valve closure sequence is strongly related to the presence of a left-sided conduction delay. The mitral-tricuspid valve closure sequence is unrelated to a conduction delay but can be reversed by relative differences in the severity of systolic dysfunction and filling pressures between the two ventricles. PMID- 8459065 TI - Effects of induced asynchrony on left ventricular diastolic function in patients with coronary artery disease. AB - OBJECTIVES: This study was designed to increase asynchrony with sequential atrioventricular (AV) pacing and to study its effects on left ventricular isovolumetric relaxation, rapid filling and stiffness. BACKGROUND: Left ventricular nonuniformity is a major determinant of diastolic function. METHODS: Thirteen patients with coronary artery disease were studied by simultaneous equilibrium radionuclide angiography and cardiac catheterization during atrial and AV pacing. Ejection fraction and peak filling rate were measured by radionuclide angiography. Regional analysis was obtained by analyzing time activity curves of four left ventricular sectors; systolic and diastolic asynchrony were evaluated as the coefficient of variation of time to end-systole and, respectively, time to peak filling rate in the four sectors. Cardiac index and left ventricular pressure were measured with high fidelity catheters at cardiac catheterization. The time constant of isovolumetric relaxation was derived from left ventricular pressure. Pressure-volume loops were assembled and constants of chamber stiffness were computed. RESULTS: Atrioventricular pacing led to a decrease in cardiac index (3.7 +/- 0.9 to 3.3 +/- 0.8 liters/min per m2, p = 0.01) and peak filling rate (352 +/- 125 to 287 +/- 141 ml/s, p = 0.03; 2.4 +/- 0.8 to 2.0 +/- 0.8 end-diastolic counts/s, p = 0.02; 4 +/- 1.3 to 3.2 +/- 1.0 stroke counts/s, p = 0.008). The time constant of isovolumetric relaxation increased (57 +/- 10 to 64 +/- 12 ms, p = 0.04) and the global diastolic pressure volume relation shifted upward. CONCLUSIONS: Atrioventricular pacing induces left ventricular asynchrony, which is associated with a slower rate of isovolumetric relaxation. The isovolumetric relaxation lasts after the filling phase has begun, thereby reducing the rate of rapid filling. PMID- 8459066 TI - Vasovagal reactions may occur after orthotopic heart transplantation. AB - OBJECTIVES: This study evaluated the ability of patients to manifest vasovagal reactions after orthotopic heart transplantation. BACKGROUND: Paradoxic stimulation of left ventricular baroreceptors may be the afferent limb of the vasovagal reflex in humans. Orthotopic heart transplantation causes surgical denervation of these receptors and would therefore be expected to abolish the vasovagal reflex. METHODS: To attempt to confirm this hypothesis, 10 patients with orthotopic heart transplantation underwent both head-up tilt testing while resting on a saddle support and testing for parasympathetic innervation of the donor heart before and after atropine infusion. Native and donor heart sinus rates were monitored by using an esophageal pill electrode throughout tilting and during parasympathetic testing. RESULTS: Unexpectedly, seven patients had vasovagal responses at saddle support tilt testing, during which native heart rate decreased by 25 +/- 7 beats/min and mean arterial blood pressure decreased by 55 +/- 9 mm Hg. In three of these patients, there was also a decrease in donor heart rate of 23 +/- 26 beats/min. Parasympathetic testing showed possible evidence of donor heart vagal reinnervation in these patients with donor heart bradycardia during tilt but not in those with vasovagal reactions to tilt without slowing of the donor heart rate. CONCLUSIONS: Vagal efferent reinnervation can occur after orthotopic heart transplantation in humans. However, the absence of such reinnervation in some patients with vasovagal responses to tilt calls into question the role of left ventricular receptors in inducing the vasovagal reaction. PMID- 8459067 TI - Role of ventricular vagal afferents in the vasovagal reaction. PMID- 8459068 TI - Is intravenous glucocorticoid therapy better than an oral regimen for asymptomatic cardiac rejection? A randomized trial. AB - OBJECTIVES: This study assessed whether treatment with oral prednisone (bolus plus tapered doses) is comparable to intravenous methylprednisolone sodium succinate (Solu-Medrol) therapy in patients with asymptomatic moderate cardiac allograft rejection episodes without hemodynamic compromise. BACKGROUND: Intravenous Solu-Medrol therapy is frequently administered for moderate rejection episodes after heart transplantation but has not previously been compared with an oral prednisone therapy for asymptomatic cardiac rejection in a randomized trial. Compared with oral prednisone therapy, the administration of intravenous Solu Medrol is more costly and resource intensive, and it can require loss of work time for patients and the family members who accompany them to treatment. METHODS: Forty-one heart transplant patients with 43 episodes of asymptomatic moderate cardiac rejection were randomized to receive 3 days of 1,000 mg of intravenous Solu-Medrol (20 episodes) or prednisone as a bolus dose of 100 mg orally for 3 days, tapering to the previous maintenance dosage over 14 days (23 episodes). Follow-up endomyocardial biopsies were performed at 2 and 4 weeks. Infectious complications were monitored and the cost of the two forms of therapy was assessed. RESULTS: Resolution of moderate rejection occurred within 4 weeks in 19 (95%) of 20 patients treated with intravenous steroids and in 21 (91%) of 23 patients treated with oral prednisone. No significant difference in infectious complications occurred between the two groups in the ensuing 3 months after therapy. The cost of the oral prednisone therapy was $6.30 compared with the cost of $180 to $966 for administration of intravenous Solu-Medrol. CONCLUSIONS: Oral prednisone (bolus plus tapered doses) appears to be as effective and to have similar infectious complication rates as intravenous Solu-Medrol for the treatment of asymptomatic cardiac rejection. The convenience and lower cost of oral prednisone therapy may warrant its routine use for this type of cardiac rejection. PMID- 8459069 TI - Effect of antihypertensive treatment on endothelium-dependent vascular relaxation in patients with essential hypertension. AB - OBJECTIVES: This study was designed to determine whether antihypertensive treatment can restore the impaired endothelium-dependent vasodilation of patients with essential hypertension. BACKGROUND: The endothelium regulates vascular tone through the release of vasoactive agents that act on the underlying vascular smooth muscle. This endothelial function is impaired in certain cardiovascular conditions, including essential hypertension. METHODS: The vascular responses to acetylcholine (endothelium-dependent vasodilator, 7.5, 15 and 30 micrograms/min) and sodium nitroprusside (direct dilator of smooth muscle, 0.8, 1.6, 3.2 micrograms/min) were studied in 15 patients (11 men and 4 women with a mean age of 54.1 +/- 12 years) on two occasions: after withdrawal of medications, when the patients were hypertensive, and during the medical treatment that reduced blood pressure to within normal limits in each patient. The results were compared with those obtained in 15 normal control subjects (10 men and 5 women with a mean age of 52.3 +/- 7 years). Drugs were infused into the brachial artery, and forearm blood flow response was measured by strain gauge plethysmography. RESULTS: The blood flow and vascular resistance responses to acetylcholine were significantly reduced in the hypertensive patients (p < 0.0001); maximal forearm flow (ml/min per 100 ml) was 7.0 +/- 4 ml in the patients and 16.7 +/- 5 in the control subjects (p < 0.005). However, no significant differences between groups were observed in the responses to sodium nitroprusside. In patients with essential hypertension, the vascular responses to acetylcholine and sodium nitroprusside were not modified by medical therapy. Maximal forearm flow with acetylcholine (ml/min per 100 ml) was 7.2 +/- 2 during antihypertensive therapy and 7.0 +/- 4 after medication withdrawal. CONCLUSIONS: Clinically effective antihypertensive therapy does not restore the impaired endothelium-dependent vascular relaxation of patients with essential hypertension. This indicates that such endothelial dysfunction is either primary or becomes irreversible once the hypertensive process has become established. PMID- 8459070 TI - Response of human coronary arteries to acetylcholine after injury by coronary angioplasty. AB - OBJECTIVES: The aim of this study was to investigate the effect of intracoronary administration of acetylcholine on large epicardial vessels 8 days after successful coronary angioplasty. BACKGROUND: Intracoronary infusion of acetylcholine causes vessel dilation in patients without angiographic evidence of coronary atherosclerosis, whereas it causes constriction of stenotic coronary branches. These findings were interpreted as evidence of endothelial dysfunction in patients with coronary atherosclerosis. METHODS: Eight patients who underwent successful single-vessel coronary angioplasty of the proximal left anterior descending artery were studied. Eight days after coronary angioplasty at the time of follow-up coronary angiography, intracoronary acetylcholine was infused (1 ml/min for 2 min) at concentrations ranging from 10(-7) to 10(-4) mol/liter. The diameter of the angioplasty and distal segments of the left anterior descending artery and that of the proximal and distal segments of the circumflex artery (control artery) were measured using computerized edge detection angiography. RESULTS: All patients showed a dose-dependent constriction in response to acetylcholine and experienced chest pain and ST segment changes. Intracoronary nitroglycerin (300 micrograms) relieved the effects of acetylcholine. The maximal tolerated dose of acetylcholine (10(-6) mol/liter in three patients, 10(-5) mol/liter in three patients and 10(-4) mol/liter in two patients) induced a mild constriction of the angioplasty segment from 1.84 +/- 0.11 mm to 1.52 +/- 0.13 mm (p < 0.02) similar to that of the proximal segment of the control artery (from 2.42 +/- 0.23 to 2.07 +/- 0.19 mm, p < 0.02). However, the degree of constriction of the vascular segments distal to the angioplasty site (from 1.24 +/- 0.09 to 0.62 +/- 0.13 mm, p < 0.01) was significantly greater (p < 0.05) than that observed in the distal segments of the control artery (from 1.23 +/- 0.03 to 0.71 +/- 0.01 mm, p < 0.01) and resulted in transient total occlusion in two patients. CONCLUSIONS: Eight days after coronary angioplasty, coronary segments distal to the dilated site but not at the dilated site are hyperreactive to acetylcholine. The response of epicardial coronary arteries to acetylcholine is influenced not only by the dose of acetylcholine and the endothelial function (as currently believed) but also by the location of the coronary segment considered, confirming the presence of a profound alteration of distal coronary vessels. PMID- 8459071 TI - Coronary artery perforation during excimer laser coronary angioplasty. The percutaneous Excimer Laser Coronary Angioplasty Registry. AB - OBJECTIVES: The aim of this study was to analyze the risk of vessel perforation during excimer laser angioplasty. BACKGROUND: Vessel perforation is a serious complication of angioplasty. METHODS: A total of 764 patients had 858 stenoses treated with excimer laser angioplasty. Laser catheters had a diameter of 1.4, 1.7 or 2 mm. Laser energy was delivered in pulses of 135 ns, at a frequency of 25 s-1 and at a fluence of 30 to 60 mJ/mm2. Follow-up angiography was requested for all patients who did not require emergency bypass surgery. RESULTS: In the 764 consecutive patients treated with excimer laser coronary angioplasty, vessel perforation occurred in 23 patients (3%). Nine patients had a major complication resulting directly from vessel perforation (cardiac tamponade, myocardial infarction or need for bypass surgery) and 14 had no clinical complications after successful sealing of the puncture site. No patient with a perforation died. Multivariate analysis showed that bifurcation lesions (odds ratio [OR] = 3.5; p = 0.049), diabetes mellitus (OR = 3.15; p = 0.029) and female gender (OR = 2.86; p = 0.013) were associated with an increased risk of vessel perforation. Lesions > 10 mm in length (OR = 0.45; p = 0.206), calcified stenoses (OR = 0.26; p = 0.088) and saphenous vein graft lesions (OR = 0.50; p = 0.295) were not at increased risk. Vessel perforation was seen in 10 (8.3%) of 120 lesions in which the laser catheter was equivalent in diameter to the target vessel (< or = 0.5 mm smaller in size) but in only 8 (1.5%) of 525 lesions in which the laser catheter was > 1 mm smaller than the target vessel (p = 0.001). CONCLUSIONS: Most lesions thought to be suitable for excimer laser treatment are not at increased risk of perforation. The complication may be avoided by improved patient and laser catheter size selection. PMID- 8459072 TI - Mechanisms of restenosis and redilation within coronary stents--quantitative angiographic assessment. AB - OBJECTIVES: This study was designed to assess the relative contributions of intimal hyperplasia and stent compression to the lumen narrowing seen after intracoronary stenting and to determine whether the lumen enlargement produced by angioplasty of in-stent restenosis results primarily from compression or extrusion of intimal hyperplasia through the stent or from additional stent expansion. BACKGROUND: Palmaz-Schatz stent placement outwardly displaces plaque and eliminates elastic vessel recoil to provide a large and smooth lumen. Some degree of late lumen narrowing occurs within each stent and causes significant restenosis (> or = 50% stenosis) in 25% to 30% of treated lesions. It has not been clear, however, whether this narrowing results from stent compression (crush) or from in-stent intimal hyperplasia. Because the Palmaz-Schatz stent has a distinct radiographic shadow, it is possible to determine the late diameter of both the stent and the enclosed vessel lumen to assess the relative contributions of these two processes. METHODS: From cineangiograms, initial (after stenting) and late (follow-up) lumen and stent diameters were examined in 55 patients (59 stents, group I) who had both immediate and 6-month (192 +/- 117 days) angiography. Lumen and stent diameter were also examined before and after dilation in 30 patients (30 stents, group II) who underwent angioplasty of severe in-stent restenosis. RESULTS: Late loss in minimal lumen diameter was 0.99 +/- 0.87 mm for group I despite only a slight (0.03 +/- 0.23-mm) reduction in the corresponding stent diameter. After redilation for in-stent restenosis, the acute gain in minimal lumen diameter was 1.51 +/- 0.82 mm for group II, again without appreciable increase (0.06 +/- 0.20 mm) in stent diameter. CONCLUSIONS: Restenosis after intracoronary Palmaz-Schatz stenting appears to be due predominantly to lumen encroachment by intimal hyperplasia within the stent, with minimal contribution of stent compression. Lumen enlargement after coronary angioplasty of in-stent restenosis appears to be due primarily to compression or extrusion of intimal hyperplasia through the stent, or both, rather than to further stent expansion. PMID- 8459073 TI - Long-term angiographic follow-up of normal and minimally diseased saphenous vein grafts. AB - OBJECTIVES: We sought to ascertain the long-term fate of saphenous vein grafts known to be angiographically normal or minimally diseased 5 years after operation. This information may prove helpful in the management of such grafts at reoperation. BACKGROUND: Patients undergoing a second coronary bypass operation frequently have one or more saphenous vein grafts that remain widely patent. It is common practice during such reoperations to replace all vein grafts that are older than 5 years, including those with little or no angiographic stenosis, because of the risk of late vein graft closure. However, the long-term behavior of these angiographically normal or minimally diseased vein grafts has not been well elucidated. METHODS: Sixty-two patients with a total of 131 angiographically normal or minimally diseased (< 35% diameter narrowing) vein graft segments studied 6.1 +/- 2.1 years (mean +/- SD) after coronary bypass operation were identified by reviewing the cardiac catheterization records of the Veterans Affairs Medical Center, Buffalo, New York. Repeat angiography was performed on these patients 5.1 +/- 1.4 years after the initial postoperative angiogram (11.0 +/- 2.0 years after operation). RESULTS: On restudy, 53% of the vein grafts remained normal or only minimally diseased, 18% showed moderate stenosis (35% to 69%), 8% were patent but with severe disease (70% to 99%) and 21% were totally occluded. Disease progression was similar in grafts that were previously normal compared with those that had minimal disease. CONCLUSIONS: The long-term patency of angiographically normal or minimally diseased vein grafts is good (79% 5-year patency rate, 71% free of severe disease). The presence of minimal disease does not adversely affect long-term patency. The recommendation to replace normal or minimally diseased vein grafts during late reoperation should be reevaluated. PMID- 8459074 TI - Percutaneous angioscopy of saphenous vein coronary bypass grafts. AB - OBJECTIVES: We compared the results of percutaneous angioscopy and angiography for detecting critical elements of surface lesion morphology in 21 patients undergoing balloon angioplasty of saphenous vein coronary bypass grafts. BACKGROUND: Angiography remains the standard for diagnosing and treating intravascular pathology associated with atherosclerotic coronary artery disease. It has been demonstrated that coronary angioscopy is more sensitive for identifying more complex atherosclerotic plaques and intracoronary thrombi in native coronary arteries. METHODS: Angioscopy and angiography were performed before and after angioplasty of "culprit lesions" in bypass grafts. All but one of the patients had unstable angina. The mean age of the saphenous vein coronary bypass grafts was 10.1 +/- 2.4 years (range 5 to 15). RESULTS: Restenosis at a prior angioplasty site was present in seven patients. Intravascular thrombi were seen by angioscopy in 15 (71%) of 21 versus 4 (19%) of 21 grafts by angiography (p < 0.001). Dissection was identified by angioscopy in 14 (66%) of 21 versus 2 (9.5%) of 21 grafts by angiography (p < 0.01). The presence of friable plaque lining the lumen surface of the vein graft was detected by angioscopy in 11 (52%) of 21 versus 4 (19%) of 21 grafts by angiography (p < 0.05). There was no correlation between age of the bypass graft and the finding of friable plaque. CONCLUSIONS: We conclude that angioscopy is superior to angiography for detecting complex lesion morphology in bypass grafts and that the presence of friable plaque does not preclude an uncomplicated angioplasty procedure. PMID- 8459076 TI - Assessment of autonomic function in patients with neurally mediated syncope: augmented cardiopulmonary baroreceptor responses to graded orthostatic stress. AB - OBJECTIVES: The purpose of this study was to assess vagal tone and cardiopulmonary baroreceptor activity in patients with tilt-induced neurally mediated syncope. BACKGROUND: The causes of individual susceptibility to orthostatic stress leading to recurrent neurally mediated syncope remain obscure. The trigger for sympathetic withdrawal and increased vagal activity is believed to be stimulation of ventricular mechanoreceptors. METHODS: Seventeen patients (mean age 50.6 years) with recurrent syncope and a positive response on a 45-min 60 degrees head-up tilt test were compared with a control group of 17 patients (mean age 47.5 years) with unexplained syncope and negative tilt test findings. Vagal activity was assessed by high pressure baroreceptor testing and by temporal and spectral analysis of heart rate variability during Holter ambulatory electrocardiographic monitoring. Cardiopulmonary baroreceptor sensitivity was assessed by measurement of forearm vascular responses to lower body negative pressure. RESULTS: Mean high pressure baroreceptor sensitivity was 16.4 +/- 12.2 ms/mm Hg in the group with a positive tilt test response compared with 15.1 +/- 13.0 ms/mm Hg in the control group (p = NS). There were no significant differences between the groups in any of the temporal or spectral measures of heart rate variability. The increase in forearm vascular resistance in response to lower body negative pressure was 11.5 +/- 14.2 U in patients with tilt-induced syncope and 3.5 +/- 3.2 U in the control group at -5 mm Hg, 16.8 +/- 18.6 U and 4.8 +/- 5.3 U, respectively, at -10 mm Hg and 26.4 +/- 24.3 U and 10.2 +/- 7.8 U, respectively, at -20 mm Hg (p < 0.001). CONCLUSIONS: Patients with tilt-induced neurally mediated syncope have augmented cardiopulmonary baroreceptor responses to orthostatic stress. This finding sheds new light on the etiology of neurally mediated syncope. PMID- 8459075 TI - Implantable cardioverter-defibrillator therapy in survivors of out-of-hospital sudden cardiac death without inducible arrhythmias. AB - OBJECTIVES: The aim of this study was to determine the efficacy of implantable cardioverter-defibrillator (ICD) therapy in survivors of sudden cardiac death in whom no ventricular arrhythmias can be induced with programmed electrical stimulation. BACKGROUND: Survivors of sudden cardiac death in whom ventricular arrhythmias cannot be induced with programmed electrical stimulation remain at risk for recurrence of serious arrhythmias. Optimal protection to prevent sudden death in these patients is uncertain. This study compares survival in the subset of survivors of sudden cardiac death with that of patients treated with or without an ICD. METHODS: A retrospective study was performed on 194 consecutive survivors of primary sudden death who had < or = 6 beats of ventricular tachycardia induced with programmed electrical stimulation with at least three extrastimuli. Ninety-nine patients received an ICD and 95 did not. RESULTS: There were no significant differences between the two groups in presenting rhythm, number of prior myocardial infarctions or use of antiarrhythmic agents. Patients treated with an ICD were younger (55 +/- 16 vs. 59 +/- 11 years, p = 0.03) and had a lesser incidence of coronary artery disease (48% vs. 63%, p = 0.04) and a lower ejection fraction (0.43 +/- 0.16 vs. 0.48 +/- 0.18, p = 0.04). There were no significant differences between the groups in the use of revascularization procedures or antiarrhythmic agents after the sudden cardiac death. Patients treated with an ICD had an improvement in sudden cardiac death-free survival (p = 0.04) but the overall survival rate did not differ from that of the patients not so treated (p = 0.91). A multivariate regression analysis that adjusted for the observed differences between the groups did not alter these results. CONCLUSIONS: Survivors of sudden cardiac death in whom no arrhythmias could be induced with programmed electrical stimulation remained at risk for arrhythmia recurrence. Although the proportion of deaths attributed to arrhythmias was lower in the patients treated with an ICD, this therapy did not significantly improve overall survival. PMID- 8459077 TI - Effects of oral theophylline on sick sinus syndrome. AB - OBJECTIVES: We sought to determine the effect of theophylline on cardiac pauses in sick sinus syndrome. BACKGROUND: Sick sinus syndrome, a relatively benign condition, is usually treated with pacemaker implantation without any proved effectiveness. Thus, an appropriate pharmacologic therapy would be useful. METHODS: Theophylline (200 to 400 mg/day for 1 month) was initially administered orally to 17 patients with sick sinus syndrome, which is manifested by sinus pauses of > 2.5 s. Eleven of the 17 patients subsequently received theophylline for an additional 8 to 37 months. Twenty-four-hour Holter recordings were obtained before treatment, at the end of 1 month of treatment and then at 6-month intervals. RESULTS: Theophylline decreased the frequency of sinus pauses from 256 +/- 230 to 23 +/- 62 pauses per 24 h and decreased the duration of the longest pauses from 4.7 +/- 1.8 to 2.2 +/- 0.97 s after 1 month of treatment. Subjective symptoms associated with cardiac pauses disappeared in 16 of 17 patients. Ventricular premature beats increased in frequency but did not last longer than two beats. Three patients experienced adverse effects. Nine of the 11 patients receiving long-term treatment had a good outcome, but 2 patients required a pacemaker because of the reappearance of long sinus pauses. CONCLUSIONS: The results suggest that oral theophylline may be beneficial for the treatment of patients with sick sinus syndrome. PMID- 8459078 TI - Computer-guided surgery for tachyarrhythmias in children: current results and expectations. AB - OBJECTIVES: The purpose of this report is to summarize our entire surgical experience in the treatment of tachyarrhythmias in children. We emphasize our application of a newer computerized mapping system for use in both the electrophysiology laboratory and the operating room to localize points of activation of the tachyarrhythmias. BACKGROUND: A retrospective review was undertaken to examine the results of operative procedures in 290 children undergoing surgical treatment for tachyarrhythmias from 1977 to the present. METHODS: Operative procedures were performed in 290 children and consisted of the following: surgical ablation of accessory pathways of the Kent bundle type (210 children); surgery with cryoablation for atrial ectopic tachycardia (35 children); surgical excision or cryoablation, or both, for ventricular tachycardia (26 children); cryoablation for the permanent form of junctional reciprocating tachycardia (15 children) and atrioventricular (AV) node reentrant tachycardia (4 children). RESULTS: The surgical cure rate for accessory pathway tachycardia in the era before computerized mapping was 80% (41 patients) in the period from 1977 to 1982 and 95% (86 patients) in the period from 1982 to 1988. This rate improved to 100% (83 patients) after the advent of the computerized mapping technique. These improved results are probably due to a combination of factors, including increasing experience in electrophysiologic mapping and surgery, and cannot be attributed to the computerized mapping system alone. Surgical cure or major improvement in symptoms was documented in 33 (94%) of 35 patients with atrial ectopic tachycardia. Surgical cure was accomplished in 25 (96%) of 26 patients with the complex form of ventricular tachycardia. In 19 patients with the permanent form of junctional reciprocating tachycardia and the more typical AV node reentrant tachycardia, the surgical cure rate was 100%. CONCLUSIONS: In all forms of supraventricular reentrant tachycardia that occur in children, preoperative computerized mapping techniques combined with intraoperative computerized mapping and surgical ablation can eliminate tachycardia at a success rate of close to 100%. Computerized mapping techniques are less accurate in patients with atrial ectopic tachycardia because of multiple foci and a broader surface area to be mapped. This experience demonstrates that excellent results can be achieved in the surgical treatment of tachyarrhythmias in children. PMID- 8459079 TI - Color flow imaging compared with quantitative Doppler assessment of severity of mitral regurgitation: influence of eccentricity of jet and mechanism of regurgitation. AB - OBJECTIVES: To determine the influence of jet eccentricity and mechanism of mitral regurgitation, we examined 1) the relation between jet extent and severity of mitral regurgitation, and 2) the use of Doppler color flow imaging for quantitation of mitral regurgitation. BACKGROUND: Doppler color flow imaging is widely used to assess mitral regurgitation. However, whether, how and in which subgroups it can quantify regurgitation remain controversial. METHODS: In 80 patients with mitral regurgitation, results of color flow Doppler studies obtained in two orthogonal apical views were prospectively compared with quantitative Doppler measurement of the regurgitant volume and the regurgitant fraction. Comparisons were made according to the eccentricity of the jet (group 1 eccentric jets, n = 29; group 2 central jets, n = 51); group 2 was subdivided according to the mechanism of mitral regurgitation (group 2a organic, n = 27; group 2b ischemic or functional, n = 24). RESULTS: Globally, weak correlations were found between regurgitant volume and jet area (r = 0.57) and regurgitant fraction and jet area/left atrial area ratio (r = 0.65). Groups 1 and 2 showed a correlation between regurgitant volume and jet area (r = 0.68 and r = 0.65, respectively, p < 0.0001), but the slope was steeper in group 2 than in group 1 (0.22 vs. 0.06, p < 0.0001). The same jet area corresponded to more severe regurgitation in group 1 than in group 2 (jet > or = 8 cm2, regurgitant volume 113 +/- 55 vs. 43 +/- 21 ml, p < 0.0001). Similarly, for comparable regurgitant volumes (24 +/- 22 vs. 29 +/- 11 ml, p = NS), group 2a had a smaller jet area than did group 2b (5.3 +/- 6 vs. 9.6 +/- 6 cm2, p < 0.02). Quantitation of regurgitation by Doppler color flow imaging was unreliable in group 1; in group 2b, the regression line between regurgitant fraction and jet area/left atrial area ratio was close to the identity line. CONCLUSIONS: Mitral regurgitant jet eccentricity and mechanism influence jet extent. The same regurgitant volume produces smaller jet areas for eccentric compared with central jets and for central organic compared with ischemic or functional regurgitation. Quantitation of regurgitation using Doppler color flow imaging is possible in ischemic or functional regurgitation but inappropriate in eccentric jets, where quantitative Doppler study should be recommended. PMID- 8459080 TI - Prevalence of aortic valve abnormalities in the elderly: an echocardiographic study of a random population sample. AB - OBJECTIVES: This study was undertaken to elucidate the prevalence of aortic valve abnormalities in the elderly. BACKGROUND: The age of persons treated actively for valve disorders is increasing. More information is needed about the prevalence of aortic valve disease in old age. METHODS: Randomly selected men and women in the age groups 75 to 76, 80 to 81 and 85 to 86 years (n = 501) participating in the Helsinki Ageing Study were studied with imaging and Doppler echocardiography. Additionally, 76 persons 55 to 71 years of age were included. The systolic aortic valve area was calculated by the continuity equation. The velocity ratio (peak velocity in the left ventricular outflow tract/peak velocity across the aortic valve) was a supplementary criterion for aortic stenosis. Valve regurgitation and cusp calcification were assessed visually. RESULTS: Evaluation of the aortic valve was possible in 552 persons (96%). Mild calcification was found in 222 (40%) and severe calcification in 72 (13%). Two persons (0.4%) had an aortic valve prosthesis. Critical native valve stenosis (calculated aortic valve area < or = 0.8 cm2 and velocity ratio < or = 0.35) was found in 12 persons (2.2%). Six of these were symptomatic and potentially eligible for valvular surgery. All persons with aortic valve stenosis were in the three oldest age groups. The prevalence of critical aortic valve stenosis was 2.9% (95% confidence interval 1.4% to 5.1%) in the group 75 to 86 years of age. Aortic regurgitation, mostly mild, was found in 29% of the entire study cohort. CONCLUSIONS: Calcific aortic valve stenosis constitutes a significant health problem in the elderly. Only a minority of those with potentially operable aortic valve stenosis undergo surgery. PMID- 8459081 TI - Transesophageal echocardiography in right-sided endocarditis. AB - OBJECTIVES: Our aim was to determine the diagnostic value of transesophageal echocardiography in right-sided endocarditis. BACKGROUND: Recent studies have demonstrated that transesophageal echocardiography is superior to transthoracic echocardiography in the detection of vegetations associated with left-sided endocarditis. Its diagnostic value in right-sided endocarditis has not been established. METHODS: Transthoracic and transesophageal echocardiography were prospectively performed in 48 patients who met specific criteria for the suspicion of right-sided endocarditis. All were intravenous drug abusers. RESULTS: Vegetations were found in 22 of 48 patients by both transthoracic and transesophageal echocardiography. The vegetations were more precisely characterized by transesophageal echocardiography in 14 (63%) of 22 patients. In the remaining 26 patients, no vegetations were found by either transthoracic or transesophageal echocardiography. No statistically significant differences were found between the two techniques in the assessment of tricuspid regurgitation, which was detected in 21 (44%) of 48 patients. CONCLUSIONS: We conclude that transesophageal echocardiography does not improve the diagnostic accuracy of transthoracic echocardiography in the detection of vegetations associated with right-sided endocarditis in intravenous drug abusers. Transesophageal echocardiography may not be indicated as a routine procedure in patients suspected of having right-sided endocarditis. PMID- 8459082 TI - Transesophageal echocardiographic diagnosis of right to left shunting across the foramen ovale in adults without prior stroke. AB - OBJECTIVES: The purpose of this study was to estimate the prevalence of potential right to left interatrial shunting and to quantify the morphologic characteristics of the fossa ovalis in adults without a prior history of stroke or systemic embolism. BACKGROUND: Paradoxic embolization through a patent foramen ovale is an important cardiac mechanism for embolic stroke. Although anatomic and physiologic data obtained by transesophageal echocardiography increase the frequency of demonstration of potential cardiac sources of systemic embolism and occasionally can conclusively demonstrate the mechanism for embolic stroke, the prevalence and prognostic implications of these findings in neurologically healthy persons are still being actively investigated. METHODS: Intraoperative transesophageal saline contrast echocardiography was performed on 50 adult patients without prior history of stroke or systemic embolism who were undergoing elective cardiovascular surgery. RESULTS: No patient had a manifest atrial septal defect by right heart oximetric measurements or transesophageal Doppler echocardiographic examination. Eleven of the 50 patients demonstrated right to left atrial passage of saline contrast medium during apnea or after release of 20 cm H2O positive airway pressure, signifying patency of the foramen ovale. These 11 patients with a patent foramen ovale had increased total excursion of the flap valve (septum primum) of the fossa ovalis (1.3 +/- 0.7 cm) compared with findings in the 39 patients without a patent foramen ovale (0.3 +/- 0.5 cm, p < 0.001). All patients with a patent foramen ovale exhibited some mobility of the septum primum and 73% of these patients had > or = 1 cm total excursion of the septum primum. In contrast, 56% of patients without a patent foramen ovale exhibited no motion of the septum primum out of the plane of the atrial septum. The maximal diameter of the fossa ovalis was greater in patients with (1.4 +/- 0.4 cm) than in patients without (1.0 +/- 0.3 cm, p < 0.003) a patent foramen ovale. CONCLUSIONS: Hypermobility of the septum primum and enlargement of the fossa ovalis are morphologic findings that occur in the presence of a patent foramen ovale. PMID- 8459083 TI - Eighteen-hour preservation of rat hearts with hexanol and pyruvate cardioplegia. AB - OBJECTIVES: The aim of this study was to evaluate the effectiveness of 1-hexanol as an arresting agent and pyruvate as a substrate in a cardioplegic solution. BACKGROUND: Heart transplantation is limited in part by the short preservation time of donor hearts. Better preservation techniques would improve patient survival and the time and geographic area for using donor hearts. We previously showed that a cardioplegic solution containing ethanol and pyruvate was superior to a conventional high potassium cardioplegic solution in 24-h cold storage of hamster hearts. Hexanol, a more potent arresting agent than ethanol, might be a more suitable alcohol. METHODS: Rat hearts were arrested and stored for 18 h at 4 degrees C with an ethanol (3 vol% = 510 mmol/liter) or 1-hexanol (4 mmol/liter) and pyruvate (10 mmol/liter) cardioplegic solution, St. Thomas' Hospital solution and Stanford solution and subsequently reperfused for 1 h at 35 degrees C. In other groups of hearts, basal oxygen consumption and rest intracellular calcium (Indo 1 technique) were evaluated during ethanol-, hexanol- and potassium-induced cardiac arrest. RESULTS: The percent recovery of left ventricular developed pressure and rate-pressure product were significantly better with the hexanol cardioplegic solution (67 +/- 21% and 58 +/- 19%, respectively; p < 0.05 for all comparisons) compared with the ethanol (10 +/- 7% and 5 +/- 4%), St. Thomas' Hospital (14 +/- 6% and 10 +/- 5%) and Stanford solutions (2 +/- 2% and 2 +/- 1%, respectively). Exclusion of ethanol and hexanol from storage solutions did not influence functional recovery. Values for oxygen consumption after 15- and 30-min ethanol- and hexanol-induced arrest were significantly lower than those after potassium-induced cardiac arrest. There was no difference in the rest intracellular calcium during cardiac arrest induced by the three arresting agents. CONCLUSIONS: A hexanol and pyruvate cardioplegic solution was more favorable than ethanol or conventional solutions for long-term cold storage of rat hearts. The beneficial effects of hexanol may have been provided in part by lower energy consumption during hexanol-induced cardiac arrest. These results may have implications for preservation of hearts for heart transplantation. PMID- 8459085 TI - Effects of cyclosporine, prednisolone and aspirin on rat autoimmune giant cell myocarditis. AB - OBJECTIVES: Preventive effects of cyclosporine, prednisolone and aspirin on autoimmune giant cell myocarditis in rats were investigated. BACKGROUND: The therapeutic efficacy of immunosuppressants for human myocarditis is controversial. Although harmful effects of immunosuppressive therapy on experimental viral myocarditis have been reported, the effects on autoimmune myocarditis have not been investigated. Recently, a novel experimental autoimmune myocarditis model characterized by congestive heart failure and multinucleated giant cell has been established. Using this model, the preventive effects of cyclosporine, prednisolone and aspirin on autoimmune myocarditis were investigated. METHODS: Lewis rats were immunized with cardiac myosin in complete Freund's adjuvant on days 0 and 7. In experiment 1, four groups of seven rats each were established. Rats in each group received for 21 days intraperitoneal injections of either 1) phosphate-buffered saline solution, 1 ml/day (control); 2) cyclosporine, 20 mg/kg body weight per day (cyclosporine 20); 3) prednisolone, 4 mg/kg per day; or 4) aspirin, 15 mg/kg per day. In experiment 2, two additional groups (five rats each) received for 21 days an injection of cyclosporine, 1 or 5 mg/kg per day (cyclosporine 1 and cyclosporine 5, respectively). All rats were killed on day 21, when histopathologic studies were performed and the titers of antimyosin antibodies were measured. RESULTS: The rats in the control, prednisolone and aspirin groups became ill and immobile in week 3. In comparison, rats in the cyclosporine 5 and 20 groups were still active until death was induced. Heart weight/body weight, lung weight/body weight and liver weight/body weight ratios in the rats in the cyclosporine 5 and cyclosporine 20 groups were significantly lower than those in the control group, and no differences were detectable among rats in the control, prednisolone and aspirin groups. The rats in the latter three groups and the cyclosporine 1 groups showed severe myocarditis with multinucleated giant cells. However, myocarditis was effectively prevented in the rats in the cyclosporine 5 and 20 groups. The histologic scores in each group were 2.91 in the control group, 2.14 in the prednisolone group, 2.91 in the aspirin group and 0.02, 2.58 and 0.07, respectively, in the cyclosporine 20, 1 and 5 groups. Production of antimyosin antibodies was remarkably suppressed in rats in the cyclosporine 5 and 20 groups in comparison with values in all other groups. CONCLUSIONS: Autoimmune myocarditis is preventable by cyclosporine but not by prednisolone or aspirin in usual dosages. PMID- 8459084 TI - Myocardial infarct extension during reperfusion after coronary artery occlusion: pathologic evidence. AB - OBJECTIVES: The goal of this study was to demonstrate myocardial infarct extension during reperfusion within the same animal. BACKGROUND: Whether myocardial reperfusion can result in the extension of myocardial necrosis remains controversial. The transformation of reversibly injured myocytes into irreversibly damaged cells after reperfusion has been difficult to demonstrate pathologically. METHODS: New Zealand White rabbits (Group I, n = 10) were subjected to 30 min of coronary artery occlusion and 180 min of reperfusion. Horseradish peroxidase, a tracer protein that permeates the sarcolemma of irreversibly injured myocytes, was used to quantitate myocyte necrosis at the beginning of reperfusion. Within the same heart, infarct size was measured after 180 min of reperfusion by triphenyltetrazolium chloride (TTC) staining. In separate experiments to demonstrate the validity of the model, rabbits were subjected to 30 min of coronary occlusion, followed by intravenous infusion of horseradish peroxidase and rapid induction of death (Group II) or 30 min of occlusion, 180 min of reperfusion with horseradish peroxidase administered after 180 min of reperfusion and TTC staining after induced death (Group III). RESULTS: In Group I, infarct size at the onset of reperfusion, delineated by horseradish peroxidase, measured 45.3 +/- 2.8% of the area of risk and was significantly less than TTC-delineated infarct size after 180 min of reperfusion (59.8 +/- 3.3%, p = 0.0002). By electron microscopy, border areas within the ischemic bed demonstrated irreversibly injured horseradish peroxidase-positive myocytes adjacent to irreversibly injured horseradish peroxidase-negative myocytes, suggesting that further cell death occurred during reperfusion. In Group II, infarcts delineated by horseradish peroxidase after 30 min of coronary occlusion were similar in size to infarcts measured by this tracer in Group I. In Group III, infarcts delineated by horseradish peroxidase at 180 min of reperfusion were similar in size to infarcts measured by TTC and similar to TTC-delineated infarcts measured at 180 min of reperfusion in Group I. CONCLUSIONS: These results provide evidence that there is a subset of myocytes in border areas within the ischemic region that are viable at the beginning of reperfusion but subsequently progress to irreversible injury during the reperfusion period. PMID- 8459086 TI - Assessment of coronary conductance and resistance vessel reactivity in response to nitroglycerin, ergonovine and adenosine: in vivo studies with simultaneous intravascular two-dimensional and Doppler ultrasound. AB - OBJECTIVES: The aim of this study was to determine the differential effects of nitroglycerin, ergonovine and adenosine on the resistance vessels in vivo by using a Doppler-tipped guide wire in combination with an ultrasound imaging catheter. BACKGROUND: Catheter-based two-dimensional intravascular ultrasound yields images of the coronary arteries from which cross-sectional areas can be measured. Intravascular Doppler ultrasound techniques allow measurement of coronary blood flow velocity. The simultaneous use of the two techniques can yield anatomic and physiologic information on conductance and resistance vessels but has not been tried in the coronary arteries. METHODS: In 15 dogs, we studied coronary flow and vascular reactivity in response to pharmacologic agents using two approaches: 1) a 30-MHz, 4.3F imaging catheter placed alongside a 0.018-in. (0.046 cm) Doppler wire in the circumflex or left anterior descending coronary artery (n = 5); 2) the ultrasound imaging catheter introduced directly over a 0.014-in. (0.036 cm) Doppler wire (n = 10). Vasodilator and vasoconstrictor responses were studied by using intracoronary nitroglycerin (50, 100 and 200 micrograms), ergonovine (200 micrograms) and adenosine (6 mg). RESULTS: Nitroglycerin caused a dose-dependent increase in epicardial coronary artery cross-sectional area and, to a lesser extent, in average peak flow velocity, resulting in an increase in volumetric coronary blood flow of 39% and 50% at the doses of 100 and 200 micrograms, respectively. With these doses of nitroglycerin, the decrease in diastolic to systolic velocity ratio and the increased change in cross-sectional area from end-diastole to end-systole suggested an enhanced epicardial coronary artery compliance. With ergonovine, a 12% reduction in epicardial coronary artery cross-sectional area was seen, without a significant change in average peak velocity, resulting in a 15% decrease in volumetric coronary blood flow. Adenosine caused a 270% increase in average peak velocity but no change in epicardial coronary artery cross-sectional area, resulting in a 270% increase in volumetric blood flow. CONCLUSIONS: This study demonstrates that nitroglycerin and ergonovine predominantly influence coronary conductance arteries whereas adenosine mainly dilates coronary resistance vessels. These findings also demonstrate that the combined use of a two-dimensional and a Doppler ultrasound transducer within one catheter assembly can provide information on the differential effects of vasoactive agents on the epicardial and microvascular coronary circulation. PMID- 8459087 TI - Combined thromboxane A2 synthase inhibition and prostaglandin endoperoxide receptor antagonism limits myocardial infarct size after mechanical coronary occlusion and reperfusion at doses enhancing coronary thrombolysis by streptokinase. AB - OBJECTIVES: We sought to examine to what extent a combination of strong thromboxane A2 synthase inhibition and moderate endoperoxide receptor blockade enhances streptokinase-induced coronary thrombolysis and provides anti-ischemic activity independent from its thrombolytic activity. METHODS: Coronary thrombi, induced by crush injury and stenosis of the coronary artery, were lysed with streptokinase, 10,000 IU/kg body weight over 90 min, in anesthetized dogs receiving solvent (n = 11), ridogrel, 0.31 mg/kg intravenously, for thromboxane A2 synthase inhibition (n = 7) or ridogrel, 5 mg/kg, for additional prostaglandin endoperoxide receptor antagonism in addition to thromboxane A2 synthase inhibition (n = 7) 10 min before the administration of streptokinase. RESULTS: Thrombolytic efficacy was greatest in animals receiving both dual-acting ridogrel, 5 mg/kg intravenously, and streptokinase as evidenced by the highest incidence of high grade coronary reperfusion (solvent 3 of 11; ridogrel, 0.31 mg/kg, 5 of 7; ridogrel, 5 mg/kg, 7 of 7; p < 0.05 vs. solvent) within the shortest delay (solvent 210 min; ridogrel, 0.31 mg/kg, 85 min; ridogrel, 5 mg/kg, 37 min; p < 0.05 vs. solvent and ridogrel, 0.31 mg/kg) and the lowest incidence of reocclusion (solvent 5 of 7; ridogrel, 0.31 mg/kg, 2 of 7; ridogrel, 5 mg/kg, 1 of 7; p < 0.05 versus solvent). Myocardial infarct size after coronary artery ligation (90 min) and subsequent reperfusion (150 min) in anesthetized dogs was 49.3 +/- 4.3% versus 29 +/- 3.9% (p < 0.05 vs. solvent) of the area of the left ventricle at risk in dogs receiving solvent (n = 9) or ridogrel, 5 mg/kg intravenously (n = 10), respectively, despite similar hemodynamic characteristics, collateral blood flow and area at risk in both groups. CONCLUSIONS: Combined thromboxane A2 synthase inhibition and endoperoxide receptor antagonism 1) upgrades thrombolysis with streptokinase in canine coronary arteries, 2) limits myocardial infarct size after nonthrombotic coronary occlusion and reperfusion, and 3) may preserve ventricular function compromised by coronary occlusion through dual manipulation of the arachidonic acid cascade in blood and myocardial tissue, respectively. PMID- 8459088 TI - Dietary fish oil supplementation reduces myocardial infarct size in a canine model of ischemia and reperfusion. AB - OBJECTIVES: This study was conducted to determine whether the long-term administration of fish oil attenuates myocardial necrosis in an occlusion reperfusion model of myocardial ischemia. BACKGROUND: Omega-3 fatty acids found in fish oil have various biologic properties that may modify myocardial injury caused by severe ischemia and reperfusion. METHODS: Of 21 dogs fed an identical diet, 10 were given supplemental fish oil containing 0.06 g/kg per day of eicosapentaenoic acid for 6 weeks. Under anesthesia and open chest conditions, the left circumflex coronary artery was occluded for 90 min, followed by 6 h of reperfusion. Regional myocardial blood flow was measured with 15-microns spheres before and during occlusion and during reperfusion. The area at risk and infarct size were measured using standard staining techniques. RESULTS: In the dogs receiving supplemental fish oil, the platelet cell membrane content of eicosapentaenoic acid increased from 0.9 +/- 0.56% to 7.1 +/- 4.0% (p < 0.001). Infarct size was 29 +/- 7% in the control group and 13 +/- 3% in the fish oil group (p < 0.05). There was no significant difference in the myocardial area at risk or rate-pressure product between the control and fish oil groups. There was no difference in regional myocardial blood flow between the groups at baseline study or during coronary occlusion and reperfusion. CONCLUSIONS: Dietary fish oil supplementation significantly reduced myocardial infarct size in this model. The difference in infarct size did not appear to be related to dissimilarities in regional myocardial blood flow or determinants of oxygen consumption. Further investigation is needed to determine the nature of the protective mechanisms of omega-3 fatty acids on myocardial infarct size. PMID- 8459089 TI - Left ventricular pseudohypertrophy in cardiac tamponade: an echocardiographic study in a canine model. AB - OBJECTIVES: This study was designed to establish whether left ventricular pseudohypertrophy in cardiac tamponade can be reproducibly induced in an experimental canine model and to investigate the mechanism of its production. BACKGROUND: Past experimental and clinical studies have shown reduction of ventricular volumes resulting from cardiac tamponade. Left ventricular pseudohypertrophy, a transient thickening of myocardial walls, was recently described as a new echocardiographic sign of cardiac tamponade. METHODS: Cardiac tamponade was induced in seven anesthetized open chest dogs with serial bolus injections of 50 ml each of 0.9% saline solution into the pericardial sac. Under hemodynamic monitoring, M-mode and two-dimensional echocardiographic measurements were performed from a right parasternal window at each stage of graded cardiac tamponade. RESULTS: There was a progressive increase of interventricular septal and posterior wall diastolic thickness. Mean wall thickness (interventricular septal thickness + posterior wall thickness divided by 2) was 9.8 +/- 1.3 mm at baseline, 14.3 +/- 0.9 mm at peak tamponade and 9.0 +/- 1.5 mm after fluid withdrawal (p < 0.0001). Mean wall thickness correlated directly with the severity of cardiac tamponade, as estimated from the level of right arterial pressures (r = 0.75 and p < 0.0001), and with the decrease of left ventricular cavity volume (r = -0.67 and p < 0.0001). Left ventricular mass did not change significantly. CONCLUSIONS: Left ventricular pseudohypertrophy is a constant manifestation of cardiac tamponade in a canine model. The degree of myocardial thickening correlates with the reduction of ventricular dimensions and with the severity of hemodynamic compromise, representing a constant facet of heart remodeling in cardiac tamponade. PMID- 8459090 TI - When is bigger too big? PMID- 8459091 TI - American College of Cardiology 1993-1994 Board of Directors. PMID- 8459092 TI - Myocarditis mimicking myocardial infarction. PMID- 8459093 TI - Strategies for the treatment of thin discrete subaortic stenosis. PMID- 8459094 TI - Absence of respiration modulation of carotid sinus nerve inputs to nucleus tractus solitarius neurons receiving arterial chemoreceptor inputs. AB - The reflex responses to activation of the arterial chemoreceptors are dependent upon when in the respiratory cycle the chemoreceptor stimulus is given. To determine if the respiratory modulation of the chemoreflex occurs within the nucleus tractus solitarius (NTS), intracellular recordings were obtained in pentobarbital-anesthetized, paralyzed and mechanically ventilated cats, from 22 non-respiratory NTS cells which were depolarized following activation of the ipsilateral carotid body chemoreceptors (by close arterial injection of < 100 microliters CO2 saturated bicarbonate). Activation of the ipsilateral carotid body chemoreceptors evoked depolarizations with amplitudes of 2.9-4.6 mV and durations of 2.1-5.9 s. Three of these cells also received a convergent excitatory input from the carotid sinus baroreceptors. Carotid sinus nerve (CSN) stimulation evoked either an excitatory post-synaptic potential (EPSPs) (n = 14, 8 monosynaptic) or an excitatory/inhibitory sequence (EPSP/IPSPs) (n = 8, 1 monosynaptic). CSN evoked PSPs were separately averaged (25-50 sweeps) during periods of phrenic nerve activity and phrenic nerve silence and during periods when the lungs were inflated and when the lungs were deflated. No parameter of the CSN evoked PSPs (latency, peak amplitude, duration) was altered during periods of phrenic nerve activity or lung inflation (all P values > 0.12, Wilcoxon signed-rank test). The results suggest that there is no respiratory modulation of arterial chemoreceptor inputs by either central respiratory drive or lung stretch receptor afferent inputs at this early stage of the reflex arc. PMID- 8459095 TI - Reflex vasodilatation in the cat lip evoked by stimulation of vagal afferents. AB - In 36 cats under nembutal anaesthesia, stimulation of the central end of the cut vagus nerve caused blood flow to increase in only the ipsilateral side in six cats (17%) and in the bilateral sides in 30 cats (83%) in the lower lips. Pretreatment with hexamethonium to block nicotinic synapses in autonomic ganglia resulted in a time-dependent reduction of the reflex vasodilator response, while phentolamine, propranolol (alpha-, beta-adrenoreceptor antagonists) and tripelennamine (histamine receptor antagonist) had no effect. Pretreatment with atropine (muscarinic receptor antagonist) showed a slight, but not statistically insignificant attenuation of the reflex vasodilatation. Ipsilateral section of either the glossopharyngeal nerve root or the inferior alveolar nerve completely abolished the reflex vasodilator response elicited by central vagal stimulation. The reflex vasodilator response induced by stimulation of the central end of the cut vagus nerve was abolished by topical capsaicin application on the central cut ends of the vagus nerve but not by capsaicin on the inferior alveolar nerve. These results suggest that there is a cutaneous reflex vasodilator system that can be activated via capsaicin-sensitive afferent fibres in the vagus nerve. Parasympathetic vasodilator fibres of this system emerge from the brain stem with the glossopharyngeal nerve and reach the blood vessels in the cat mandibular lip via the inferior alveolar nerve. PMID- 8459096 TI - Hepatic vagal amino acid sensors modulate amino acid induced insulin and glucagon secretion in the rat. AB - To clarify the physiological role of vagal amino acid sensors in the liver, the effect of hepatic vagotomy and/or celiac vagotomy (sectioning of the hepatic branch and/or the celiac branches of the vagus nerve) on the secretion of insulin and glucagon after intraperitoneal injection of neutral (L-alanine, L-leucine, and L-phenylalanine), acidic (L-glutamate), or nonmetabolized (cycloleucine) acids, was examined in rats. Hepatic vagotomy enhanced both plasma glucose and glucagon concentrations after intraperitoneal injection of alanine more than those in sham-vagotomized (control) rats, while after intraperitoneal injection of leucine, hepatic vagotomy decreased plasma glucose concentrations and enhanced plasma insulin concentrations more than in control animals. These effects, following both alanine and leucine administration, were blocked by celiac vagotomy. Glutamate, phenylalanine, and cycloleucine stimulation in hepatic vagotomized rats caused no significant differences in plasma glucose, insulin, or glucagon levels as compared to those in sham-vagotomized rats. Celiac vagotomy alone did not affect plasma glucose, insulin, or glucagon concentrations after stimulation by these five amino acids. The physiological role of alanine and leucine sensors may be to prevent amino acid-induced exaggerated pancreatic hormone secretion and to maintain blood glucose homeostasis, while glutamate, phenylalanine, and cycloleucine have no effect on this pancreatic neuroendocrine system. PMID- 8459097 TI - Development of vagal innervation to the muscle of the avian gizzard. AB - The development of the vagal innervation to the gizzard has been investigated in chick embryos and young chicks. The membrane potential, first measurable on the 15th day of incubation, was -54 +/- 0.5 mV and increased with development to -67 +/- 0.4 mV. The latter value was attained 5 days after hatching and persisted thereafter. Stimulation of intramural nerves elicited a cholinergic, excitatory junction potential (EJP) for the first time, only in a small fraction of cells, on the 20th day of incubation. Within 3 days after hatching, cholinergic transmission showed the same features as in older chicks. Stimulation of the vagus nerve elicited no membrane potential responses before hatching but as early as 4 days after hatching, non-adrenergic, inhibitory junction potentials (IJPs) were evoked. In the next 10 days or so, the IJP was replaced with a cholinergic EJP as seen in mature tissues. After atropine (0.1-1 microM) treatment, both vagal and intramural nerve stimulation evoked a non-adrenergic IJP in a small fraction of cells immediately after hatching. The fraction of cells exhibiting the IJP increased with growth and reached 100% 5 days after hatching. Hexamethonium (50 or 100 microM) abolished the vagally-evoked EJPs. The vagally evoked IJPs remained unchanged after application of hexamethonium in the early days after hatching, but later they were abolished in about half of the cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8459098 TI - Responses of lumbar vasoconstrictor neurons supplying different vascular beds to graded baroreceptor stimuli in the cat. AB - Lumbar sympathetic vasoconstrictor neurons supplying skeletal muscle, hairy skin and pelvic organs were tested for their responses to carotid baroreceptor stimulation in chloralose-anaesthetized cats. Using single- and few-fibre recordings, the responses of the different types of vasoconstrictor neuron to graded steps of non-pulsatile pressure ranging from 110 to 260 mmHg in a vascularly isolated carotid sinus were analyzed quantitatively during the first 10 s of stimulation. The activity in all postganglionic muscle vasoconstrictor (MVC) neurons, preganglionic visceral vasoconstrictor (VVC) neurons and one third of the postganglionic cutaneous vasoconstrictor (CVC1) neurons was strongly depressed by maximal baroreceptor stimulation. Moreover, quantitative analysis revealed no significant differences of the baroreceptor sensitivity of MVC and CVC1 neurons as compared with VVC neurons at all levels of carotid sinus pressure. In contrast, two-thirds of the postganglionic cutaneous vasoconstrictor (CVC2) neurons exhibited a significantly weaker barosensitivity. The functional implications are discussed. PMID- 8459099 TI - Calcium induced calcium release is involved in the afterhyperpolarization in one class of guinea pig sympathetic neurone. AB - The mechanisms underlying two potassium conductances which are activated by Ca2+ influx during the action potential in sympathetic prevertebral neurones of guinea pigs have been investigated pharmacologically. One Ca-activated K+ conductance, which is present in all mammalian sympathetic postganglionic neurones, is maximal after the action potential and decays exponentially with a time constant of about 130 ms; this conductance was inhibited by apamin (50-100 nM) consistent with the involvement of SK channels. A second Ca-activated K+ conductance with much slower kinetics is present in a large subpopulation of coeliac neurones. This conductance was resistant to apamin but markedly inhibited by application of ryanodine (5-20 microM), suggesting that Ca2+ influx during the action potential triggers release of Ca2+ from intracellular stores which in turn activates a different class of K+ channel. Noradrenaline (100 microM) depressed the second K+ conductance selectively. PMID- 8459100 TI - Locus coeruleus effects on baroreceptor responsiveness and activity of neurosecretory vasopressin cells. AB - The locus coeruleus (LC) has previously been implicated in the regulation of vasopressin secretion. To further investigate this issue experiments were done in which extracellular recordings were obtained from functionally identified neurosecretory vasopressin (VP) cells of the rat supraoptic nucleus. Electrolytic lesions of the ipsilateral LC reduced the proportion of VP cells inhibited by carotid baroreceptor activation from 93% to 35%; the inhibitory effect of aortic depressor nerve stimulation was unchanged. Electrical stimulation of the LC altered the discharge probability of 20% of VP cells tested, the predominant effect being excitation. In contrast to the effects of electrolytic lesions and electrical stimulation, neither chemical inhibition nor stimulation of the LC, by local injection of neuroactive amino acids, altered VP cell baroreceptor responsiveness or spontaneous discharge. These data indicate that while fibres of passage in the LC region can influence VP cell excitability, particularly responses to carotid baroreceptor activation, LC cells do not regulate VP cell function or, by implication, the secretion of this vasoactive and antidiuretic hormone. PMID- 8459101 TI - Joint meeting of the American Association of Immunologists and the Clinical Immunology Society. Denver, Colorado, 21-25 May 1993. Abstracts. Part II. PMID- 8459102 TI - The international standard for interleukin-6. Evaluation in an international collaborative study. AB - Three ampouled preparations of interleukin-6 (IL-6) were evaluated by 12 laboratories in seven countries for their suitability to serve as the international standard of IL-6. The preparations were assayed using in vitro bioassays and immunoassays. On the basis of the results reported here, with the agreement of the participants in the study and with the authorization of the Expert Committee on Biological Standardization (ECBS) of the World Health Organization (WHO) one of the preparations (coded 89/548) was established as the international standard of IL-6. PMID- 8459103 TI - Improvement of antisera raised against complex antigen mixtures by the use of heterologous sources of antigen for immunization. AB - Polyspecific antisera against antigen mixtures are important tools for many experimental purposes. However, following immunization with extracts containing a great number of different proteins, many antigens remain non-immunogenic. Therefore, the improvement of the antibody spectrum of antisera is an essential goal in maximising the power and applicability of many serological analyses. In the present report we demonstrate that the additional use of heterologous (i.e., antigenically related, but not identical) antigen mixtures for immunization increases the variety of antibodies in polyspecific antisera as well as the antibody titer against weak immunogens. PMID- 8459104 TI - The use of monoclonal antibodies specific for seal immunoglobulins in an enzyme linked immunosorbent assay to detect canine distemper virus-specific immunoglobulin in seal plasma samples. AB - A method is described for the measurement of antigen-specific immunoglobulin in seal pup plasmas. Four monoclonal antibodies (H1a, H13a, H24b and H49a) raised against grey seal (Halichoerus grypus) immunoglobulin were used in an ELISA procedure. Levels of canine distemper virus (CDV) specific macroglobulin (IgM like protein) were found to peak approximately 10 days after the first vaccination. Levels of other smaller CDV-specific immunoglobulins (IgG like protein) also increased after vaccination. Using immunoblotting the CDV specific IgG-like protein reacted with a CDV protein, having a molecular weight of approximately 75 kDa. PMID- 8459105 TI - Cytokine-specific ELISPOT assay. Single cell analysis of IL-2, IL-4 and IL-6 producing cells. AB - In order to assess cytokine-producing cells at the single cell level, the cytokine-specific ELISPOT assay has proven to be an important and sensitive method. The purpose of this study was to adapt this method to elucidate individual cells producing murine IL-2, IL-4 or IL-6. In order to establish these cytokine-specific ELISPOT assays, IL-2-, IL-4- and IL-6-specific cDNA transfected myeloma cell lines, e.g., X63-Ag8-653 X2, X63-Ag8-653 X4 and X63-Ag8-653 X6, respectively, were used as specific cytokine-producing cells. In the IL-2 ELISPOT assay, the coating reagent, monoclonal antibody (mAb) rat IgG2a anti-mouse IL-2 (CR #40014) was used while rabbit IgG polyclonal anti-mouse IL-2 was employed for detection of IL-2 spot forming cells (SFC). The mAbs anti-mouse IL-4, BVD4-1D11 and BVD6-24G2 were selected as capture and detection antibodies for enumeration of IL-4 SFC. For the IL-6 ELISPOT assay, anti-mouse IL-6 (MP5-20F3) mAb was used for coating and MP5-32C11 mAb was used for detection of IL-6 SFC. When IL-2 producing X63-Ag8-653 X2 cells were subjected to these three different ELISPOT assays, IL-2-specific SFC were only noted with the IL-2 ELISPOT system. In the case of IL-4 SFC, only X63-Ag8-653 X4 cells formed specific spots using the tandem of BVD4-1D11 and BVD6-24G2 mAbs. IL-6-specific spots developed in MP5-20F3 mAb pre-coated wells containing X63-Ag8-653 X6 cells, when developed with mAb anti-IL-6 (MP5-32C11). Addition of cycloheximide (50 micrograms/ml) inhibited formation of IL-2, IL-4 and IL-6 SFC by approximately 90%. When an unrelated mAb was used as detection antibody in these three different cytokine-specific ELISPOT assays, IL-2-, IL-4- and IL-6-specific SFC were not detected. Further, when concanavalin A stimulated T cells from Peyer's patch of normal mice were subjected to the respective cytokine-specific ELISPOT assay, IL-2, IL-4 and IL-6 SFC were enumerated. These results have shown that cytokine-specific IL-2, IL-4 and IL-6 ELISPOT assays have now been established and will allow analysis of the frequency of cytokine-secreting cells at the single cell level. PMID- 8459106 TI - Preparation of an anti-acid sphingomyelinase monoclonal antibody for the quantitative determination and polypeptide analysis of lysosomal sphingomyelinase in fibroblasts from normal and Niemann-Pick type A patients. AB - An anti-acid sphingomyelinase monoclonal antibody has been prepared using an in vitro booster technique. The antigen, acid sphingomyelinase, was purified from human placentas by sequential chromatographic steps in the presence of the non ionic detergent Nonidet P40. This monoclonal antibody (MAB 236) precipitates specifically the enzyme activity by immunoadsorption techniques and presents the same specificity to normal and mutated sphingomyelinase in Niemann-Pick type A patients. MAB 236 is the first antibody able to precipitate the protein in the presence of detergent thereby permitting the quantitative determination of normal and mutated sphingomyelinase in tissue and cell extracts. Polypeptide analysis and quantitative determination experiments using this monoclonal antibody showed no difference between patients and normal controls. PMID- 8459107 TI - Comparison of four purification methods for the production of immunoglobulins from eggs laid by hens immunized with an enterotoxigenic E. coli strain. AB - The importance of eggs as a source of specific antibodies is well recognized. Egg yolk contains 8-20 mg of immunoglobulins (IgY) per ml. However, the major problem in isolation is removal of lipids which are present in high concentrations. A method had been developed by employing water dilution to separate the yolk plasma proteins from the granules and lipids. Further purification of IgY from plasma proteins was achieved by a protocol involving salt precipitation and ultrafiltration. The water dilution method (WD) was compared with three other methods, namely, polyethylene glycol (PEG), dextran sulphate (DS) and xanthan gum (Xan) in terms of yield, purity, ease of use, potential scaling up and immunoactivity of IgY. The WD method gave the highest yield, followed by DS, Xan and PEG methods in that order. 9.8 mg IgY/ml egg yolk was routinely obtained from the WD method compared to 4.9 mg IgY/ml egg yolk with the popular PEG method with purities of 94% and 89% respectively. Purification methods had no adverse effect on the immunoactivities of IgY. WD was also found superior in terms of ease of use and large scale production of IgY. WD method therefore provides a simple, rapid and efficient means of purifying IgY with high activity. PMID- 8459108 TI - Inactivation of HIV-infected H9 cells in whole blood preparations by lysing/fixing reagents used in flow cytometry. AB - Reagents that lyse red blood cells and fix white blood cells were tested for their ability to inactivate cell-associated human immunodeficiency virus (HIV). Whole blood was spiked with cells from an HIV-positive cell line (H9), lysed, and fixed. The cell preparations were then cocultured with T cell blasts in serial ten-fold dilutions to rescue infectious virus and measure viral titer. All commercial lysing and fixing reagents tested inactivated cell-associated HIV by 3 5 logs, while ammonium chloride had little effect. Although an additional incubation with 1% formaldehyde for 30 min did not increase the effectiveness of the commercial lysing/fixing reagents, it did inactivate cell-associated HIV in blood treated with ammonium chloride. PMID- 8459109 TI - Phenotypic and functional analysis of mucosal T cells isolated from tissue explants of rat upper respiratory tract. AB - It has been hypothesised that T cells play a central role in the pathogenesis of asthma which is characterised by chronic inflammation of the airways. In order to further study the T cells identified in situ in the airways we have developed, in the rat, a novel method for the extraction of T cells directly from the airway mucosa. The T cells actively migrate from explant tissue under the influence of exogenous IL-2 yielding sufficient cells for phenotypic and functional analysis. The T cells obtained represent a random selection of cells present at the start of culture as determined by dot blot analysis of the T cell receptor. The majority of cells were CD8+ and did not express the alpha/beta T cell receptor. In addition, the cloning efficiency of the explant T cells was extremely low (1:28) compared to that of splenic T cells (1:2) in agreement with our earlier studies on peripheral lung T cells which also demonstrated a reduced proliferative capacity. This data suggests a generalised 'immunosuppressive' milieu throughout the respiratory tract. PMID- 8459110 TI - Fractionation of schistosome antigens by high performance electrophoretic chromatography and their screening for the ability to induce Th1 lymphocyte activity. AB - The technique of high performance electrophoretic chromatography (HPEC) has been used to fractionate soluble antigens from adult Schistosoma mansoni worms on the basis of molecular weight (MW), prior to screening for their ability to stimulate T lymphocyte activity. Approximately 250 micrograms of protein were separated by continuous electrophoresis through an SDS polyacrylamide gel into 30-50 aqueous samples of minimal volume (80 microliters). Each consecutive sample contained a limited number of proteins of progressively greater MW, although the resolution of the fractionation was affected by a number of factors including acrylamide concentration, gel length, gel diameter and electrophoretic current. Following the extraction of SDS using Calbiosorb resin, the aqueous fractions were used directly to stimulate cultures of lymphocytes taken from the lymph nodes of infected or vaccinated mice. The most promising fractions were those containing proteins which induced the release of high levels of interferon-gamma relative to the extent of proliferation. This suggests that these proteins are good inducers of Th1 lymphocyte activity. PMID- 8459111 TI - Complete saturation of protamine sulphate by dsDNA is necessary in order to obtain a highly sensitive and specific anti-dsDNA ELISA. AB - A protamine sulphate (PS) pretreated solid phase coated with different amounts of dsDNA has been used to develop a sensitive, specific and reproducible anti-dsDNA ELISA. Using low concentrations of a dsDNA coat 50% of SLE sera were found to be positive and false positive reactivity due to anti-PS reactivity was found in 3/40 patients with other auto-immune diseases (OAID). In contrast, when PS was saturated with higher concentrations of dsDNA 80% of SLE sera were detected, the reproducibility of the results was better and anti-PS reactivity of OAID patients with an anti-PS reactivity disappeared. The sera of three other OAID patients contained low avidity anti-dsDNA, measured after a salt elution step in the ELISA procedure, and 2/60 patients with non-auto-immune disease exhibited a false positive anti-dsDNA reactivity since they reacted with the solid phase even in the absence of PS and dsDNA. Thus an ELISA procedure using a PS pretreated solid phase permits the sensitive, specific and reproducible measurement of anti-dsDNA antibodies only if a high concentration of dsDNA is coated on the PS and appropriate controls are performed. PMID- 8459112 TI - An immunoblotting procedure for screening glycophorins and band 3 protein in the same blots. Identification of glycophorin and band 3 variant forms. AB - An immunoblotting procedure is described which makes it possible to screen multiple blood samples for the presence of glycophorin and band 3 variant forms with altered electrophoretic mobility. The procedure can be simplified by using whole red blood cell hemolysates instead of membranes for SDS-polyacrylamide gel electrophoresis. The use of hemolysates also has the advantage that antigens sensitive to proteolysis are not degraded in vitro. The same nitrocellulose blots were used for immunoenzymatic detection of glycophorins with a set of anti glycophorin monoclonal antibodies, and for autoradiographic detection of band 3 derived bands with 125I-labeled anti-band 3 monoclonal antibody. The screening of 157 Caucasian blood samples revealed the presence of a slower-migrating form of band 3 in seven cases and variant glycophorin in one case. The variant glycophorin exhibited the features of hybrid glycophorin of B-A type. PMID- 8459113 TI - An ELISA for blood group specific exoglycosidases. AB - An enzyme-linked immunosorbent assay (ELISA) for studying erythrocyte A, B and H epitope specific exoglycosidases is described. Human blood type B erythrocyte membranes and Coffea canephora alpha-D-galactosidase were used as a model. Membrane coated microtiter wells were incubated with exoglycosidase, probed with IgM monoclonal antibody, and then with anti-murine mu chain specific alkaline phosphatase conjugate. The assay is useful for studying exoglycosidase modification of the A, B and H epitopes on human erythrocyte membranes as well as in screening prokaryotic and eukaryotic extracts for blood group active enzymes. Furthermore, this technique has the advantage of simplicity, sensitivity, and objectivity of data interpretation. PMID- 8459114 TI - Improved bioassay for the detection of porcine tumor necrosis factor using a homologous cell line: PK(15). AB - Close similarities of various physiological parameters makes the pig one of the preferred animal models for the study of human diseases, especially those involving the cardiovascular system. Unfortunately, the use of pig models to study diseases such as viral hemorrhagic fevers and endotoxic shock syndrome have been hampered by the lack of the necessary immunological tools to measure important immunoregulatory cytokines such as tumor necrosis factor (TNF). Here we describe a TNF-bioassay which is based on the porcine kidney cell line PK(15). Compared to the widely used murine fibroblastoid cell line L929, the PK(15) cell line displays a 100-1000-fold higher sensitivity for porcine TNF-alpha, a higher sensitivity for human TNF-alpha, and a slightly lower sensitivity for murine TNF alpha. Using a PK(15) bioassay we can detect recombinant TNF-alpha as well as cytotoxic activity in the supernatants of lipopolysaccharide (LPS)-activated porcine monocytes at high dilutions. This suggests that the sensitivity of the test should permit the detection of TNF in biological specimens such as pig serum. PMID- 8459115 TI - Long-term retrospective analysis of twenty-three Proplast-Teflon temporomandibular joint interpositional implants. AB - This retrospective analysis reviews 15 patients with a total of 23 Proplast Teflon interpositional implants. Most of the implants have been removed because of implant fragmentation and giant-cell inflammatory reaction. Recommendations for continued long-term care of patients with such implants are offered. PMID- 8459116 TI - Secretomotor rhinopathy after Le Fort I maxillary osteotomy. Case report. AB - Severe secretomotor (vasomotor) rhinopathy is a very uncommon nasal condition which is believed to result from marked autonomic neural imbalance to the nasal and lacrimal glands. It has not, to our knowledge, been reported after trauma or elective surgery. A patient is described who developed this condition after a Le Fort maxillary osteotomy. The clinical difficulties of establishing this diagnosis are highlighted, and contemporary management options are discussed. PMID- 8459118 TI - Ultrastructural findings in soft tissues adjacent to titanium plates used in jaw fracture treatment. AB - The present study was conducted on biopsies from soft tissues overlying titanium miniplates that were used for the treatment of jaw fractures. The aim was to investigate the morphology of liberated titanium particles and cellular or ultrastructural changes in tissues adjacent to the miniplates. Conventional transmission electron microscope (TEM) images were used for ultrastructural investigation and identification of metal-dense particles. The presence of titanium was proved by an increase in the intensity of element-specific, inelastically scattered electrons from the primary beam. The results showed that 5-8 months after insertion of the plates and screws, there was weak cellular activity within the scar tissue overlying the plates without inflammatory cells. Most of the titanium particles were located extracellularly. The ultrastructural appearance of most of these particles suggested that titanium may be shaved off the plates or screws and may undergo cellular uptake and lysosomal degradation. The partially degraded titanium particles are then left in place after the phagocytic cells have been isolated by collagenous fibers and have finally perished. PMID- 8459117 TI - The buccal fat pad in oral reconstruction. AB - The use of the buccal fat pad (BFP) as an uncovered pedicled graft to close oral defects is relatively recent. A series of 29 consecutive cases of reconstruction utilizing the BFP is presented, showing excellent results and without added surgical morbidity. Indications include defects after benign or malignant tumour resection, and the combined BFP/temporalis myofascial pedicled flap is reported as an additional option in reconstruction. Histologic findings in healed reconstruction sites indicate fibrous replacement of the fat tissue, and epithelialization of its oral surface. From the results of this series, we conclude that the use of the BFP for the reconstruction of appropriate surgical defects in the mouth is worthy of consideration. PMID- 8459119 TI - Bradycardia after orbital injury. Case report. AB - A case of severe bradycardia following orbital trauma is described. This complication caused by the oculocardiac reflex deserves attention when patients are referred for orbital trauma. PMID- 8459120 TI - A functional evaluation of patients treated for oral cancer. A prospective study. AB - The oral function of 81 consecutive patients with intraoral squamous cell carcinoma was assessed at diagnosis and during the follow-up 1-2 years after diagnosis. Patients received either radiotherapy, surgery, or radiotherapy and surgery. Speech function and tongue mobility were better among patients who received radiotherapy alone than among patients treated with surgery or combined therapy. Subjective complaints about mucositis, poor dental status, and loss of teeth were most pronounced among patients who received radiotherapy. Patients with tumor recurrence reported a poorer quality of life and found it more difficult to accept their treatment than patients with successful primary therapy. Patients with stage I tumors, notably patients treated with surgery, felt that their quality of life was good after treatment. PMID- 8459121 TI - Median cleft lip without holoprosencephaly. Case report. AB - A patient with median cleft lip is reported, but the patient showed no evidence of holoprosencephaly, which was ruled out by MRI. When the neonate's head circumference is within two standard deviations of the mean and normotelorism occurs with median cleft lip, it can be assumed that the brain is not holoprosencephalic. The importance of this cannot be overemphasized because median cleft lip is commonly associated with holoprosencephaly and severe microcephaly. The mother developed overt diabetes mellitus after the patient was born. However, infants of diabetic mothers are known to be at increased risk of giving birth to infants with holoprosencephaly. Since a prediabetic woman may sometimes give birth to large and/or malformed infants before developing overt diabetes mellitus, it is intriguing to speculate that the prediabetic state might have resulted in a forme fruste of holoprosencephaly, affecting, in this case, only the face and not the brain. PMID- 8459122 TI - Leiomyoma of the cheek. Case report. PMID- 8459123 TI - Congenital sublingual teratoid cyst. Case report. AB - A sublingual teratoid cyst was excised without complication from a 4-month-old infant. Teratoid cysts of the mouth are rare, and generally diagnosed in adults. The differential diagnosis and approach to sublingual lesions in the infant are reviewed. PMID- 8459124 TI - Collagenase and stromelysin in recurrent aphthous ulcers (RAU). AB - Six patients with recurrent aphthous ulcers were studied for the presence of matrix metalloproteinases (MMP) 1, 3, and 8 in the lesions and in the clinically unaffected control mucosa obtained from the opposite side. MMP-type specific antisera were applied in the avidin-biotin-peroxidase complex staining method. Neutrophil-type collagenase (MMP-8) was found intracellularly in the connective tissue under the necrotized epithelium, and also laterally to the ulcer in association with the basement membrane. Fibroblast-type collagenase (MMP-1) and stromelysin (MMP-3) were found in the epithelial cells adjacent to the ulcerous lesion. They were found also in the endothelium of capillary blood vessels and postcapillary venules and also in some macrophage- and fibroblast-like mononuclear cells in the lamina propria laterally to the ulcer. A small number of MMP-1 and MMP-3 positive cells were noted in the control biopsies obtained from the clinically uninvolved control mucosa. These findings suggest regional differences in the distribution of the two main collagenases, implying distinct roles in tissue destruction and remodeling. PMID- 8459125 TI - Cephalometric interpretation and assessment of facial asymmetry secondary to congenital torticollis. The significance of cranial base reference lines. AB - The anatomic basis of the facial asymmetry resulting from untreated congenital muscular torticollis is discussed, and an objective system for both clinical and cephalometric assessment and measurement is described. Symmetry is assessed by first defining a true midfacial line, which allows both measurement of existing asymmetry and planning for subsequent surgical correction, and which can be applied to clinical as well as radiologic analysis. PMID- 8459126 TI - [Study of coronary bypass using right gastroepiploic artery in diabetes complicated cases]. AB - We have conducted coronary bypass (CABG) using right gastroepiploic artery (RGEA) in 65 patients for a period of 2 years, from December 1989 to December 1991. The patients were divided into two groups; non-diabetics (group 1 or non-DM group, 42 cases including 2 borderline cases) and diabetics (group II or DM group, 23 cases comprised of 6 cases with alimentary therapy, 10 cases with oral diabetic drug therapy, and 7 cases with insulin therapy). The clinical results of both groups at a time closely proceeding surgery were studied. No apparent difference was recognized between DM and non-DM groups, which indicated that both groups were indications for CABG. Taking precautions for the prevention of postoperative infection at the surgical wound was necessary in the DM group. The 2 cases of group II which showed beads-like constrictions on angiography at weeks 4 to 8 after surgery were assumed to remain significantly problematical in terms of the degenerative degree and patency rate of the graft after a long postoperative period. Moreover, it was possible to anastomose the graft at the site proximal to the constricted site in 1 case of group II which presented a 50% constriction at the middle region of the great curvatura ventriculi by preoperative angiography. These results suggest that in selecting the use of a RGEA graft, preoperative RGEA-angiography is necessary, particularly, in the DM group. PMID- 8459127 TI - [Three cases of aortic root replacement by cryopreserved homograft with effective usage of its anterior mitral leaflet]. AB - Homograft aortic root replacement was done to three patients and the anterior mitral leaflet of the homograft was used with success in all cases. Case 1. A 37 year-old man had late-onset active prosthetic valve endocarditis with a fistula from the aortic annulus to the left atrium. The fistula was closed by using a homograft anterior mitral leaflet and the aortic root was replaced by a homograft with reimplantation of the coronary arteries. He is very well without evidence of recurrent endocarditis 29 months after the operation. Case 2. A 37-year-old man had early-onset active prosthetic valve endocarditis and developed the same fistula as case 1. He was treated successfully as in case 1. He is very well 4 months after the operation. Case 3. A 50-year-old woman, who had undergone aortic commissurotomy due to aortic valvular stenosis fifteen years before, deteriorated again. She had subvalvular membranous stenosis and a small aortic annulus. Konno Soma procedure was applied to enlarge the annulus and the aortic root was replaced by a homograft. The interventricular septal incision was closed successfully with use of the anterior mitral leaflet of the homograft. Homograft aortic root replacement was an attractive procedure for prosthetic valve endocarditis or a small aortic annulus, and the homograft anterior mitral leaflet was useful for closing the fistula due to the infection and for closing the interventricular septal incision of Konno-Soma procedure. PMID- 8459128 TI - [2 cases report of open heart surgery with non-blood transfusion in severe valvular heart disease with cardiac cachexia--the efficacy of recombinant human erythropoietin]. AB - Open heart surgery with non-blood transfusion was performed in 2 cases of severe mitral valve disease with cardiac cachexia by administering recombinant human erythropoietin (EPO). Case 1 was a 72-year-old and case 2 was a 66-year-old woman whose % usual body weight was 71-79% and Ht value on admission was 28.5-30%. Both patients were administered 9000-18000 U/week of EPO and ferrous sulfate pre- and postoperatively. In each case 800-1200 ml of autologous blood was drawn within 3 weeks preoperatively without hemodynamic change or decrease of Ht value. Both patients were received mitral valve replacement with non-blood transfusion. Preoperative administration of EPO and autologous blood preservation allowed open heart surgery with non-blood transfusion even in such a serious case as cardiac cachexia. PMID- 8459129 TI - [Case report of congenital bronchial cyst in the subsuperior segment of the right lung]. AB - A fifty-five-year-old man revealed abnormal shadow on chest X-P. Congenital Bronchial Cyst (CBC) is believed to be caused by the abnormal budding process during the early development of the foregut and after born result in formation of noninfected cysts in the lung. In this case, CBC was lined by columnarciliated epithelium and contained cartilages and bronchial mucous glands in their wall. They were located along the tracheobronchial tree and cystgraphy presented dumbbell-like change of cysts that were seen during the development stage. These findings support the past reports radiographically that CBC may result from occlusion of the proximal side of bronchus during the early development by unknown mechanism. PMID- 8459130 TI - [Successful two-staged Jatene operation for severe right ventricular dysfunction and tricuspid regurgitation after Senning operation--a case report]. AB - We report a seven-year-old boy who underwent a successful Jatene procedure seven years after Senning procedure. The modified Senning operation was performed for the treatment of transposition of the great arteries with intact ventricular septum at three years of age. However, he gradually showed the progressive right ventricular failure with tricuspid regurgitation after operation. When he was referred to our hospital, he was in severe right ventricular failure and showed massive tricuspid regurgitation simultaneously with the moderate degree of left ventricular failure. Staged pulmonary artery banding was applied to prepare the left ventricle for Jatene procedure in spite of the presence of left ventricular failure. The systolic pressure ratio of left ventricle to right ventricle was elevated to 0.91 by this banding although the left ventricular ejection fraction decreased from 43% to 30%. And Jatene procedure was successfully performed after three months of preparation period. Catheterization study after Jatene procedure revealed improved right and left ventricular functions with decrease of tricuspid regurgitation. We conclude that the Jatene procedure should be an ideal alternative in patient with right ventricular failure and/or tricuspid regurgitation after an atrial switch operation; the left ventricle could be prepared by an effective pulmonary banding in most instances. PMID- 8459131 TI - [Blunt cardiac trauma resulting in ventricular septal perforation and mitral regurgitation due to papillary muscle rupture--a case report]. AB - A 13-year-old girl was hit by a car and referred to our hospital because of progressive chest discomfort, cough, ECG abnormalities and sustained hypotension. 2-D/Doppler echocardiography recorded on admission demonstrated ventricular septal perforation with L-R shunt and mitral regurgitation due to rupture of the posterior papillary muscle and its adjacent myocardium. Patch closure of the ventricular septal perforation and fixation of the papillary muscle were performed. In five years after surgery, the patient is doing well with no echocardiographic evidence of mitral regurgitation. PMID- 8459132 TI - [A case report of left ventricular-right atrial communication due to infective endocarditis]. AB - Left ventricular-right atrial communication is a rare lesion and its etiology is almost exclusively congenital. A case of a 48-year-old woman with left ventricular right atrial communication due to infective endocarditis was presented. The communication was located at the atrioventricular portion of the membranous septum, i.e., supravalvular type, and was closed directly with mattress suture. Aortic valve replacement with 21 mm St. Jude Medical prosthesis was performed simultaneously. The postoperative course was uneventful. This complicated lesion should be surgically managed as soon as the diagnosis is confirmed. PMID- 8459133 TI - [Two successful surgical cases of total left anomalous pulmonary venous connection with intact atrial septum--a report on their operative procedures and approaches]. AB - Partial anomalous pulmonary venous connection (PAPVC) is often associated with other congenital heart diseases. Atrial septal defect, particularly, appears in about ninety percent of patients with PAPVC. Successful repairs were made in two patients of total left PAPVC with intact atrial septum. In one patient, left thoracotomy was made, and the vertical vein was anastomosed to the left atrial appendage. Cardiopulmonary bypass was not used in this case. In the other patient, median sternotomy was made, and the vertical vein was anastomosed to the posterior wall of the left atrium under cardiopulmonary bypass. Although postoperative prognosis are excellent sofar in both cases. We consider that the latter operative procedures are preferable for PAPVC not associated with atrial septal defect. In the present paper, the detailed operative procedures and approaches for these two cases are reported, and the concerning literatures are discussed. PMID- 8459134 TI - [A resected case of leiomyosarcoma of the esophagus--the diagnosis was supported with DNA content analysis]. AB - A case of leiomyosarcoma of the esophagus was reported. The tumor was located in the lower esophagus. The esophagus was very stenotic, but the mucosa was clear. We thought the tumor had not invaded the mucosa. Enucleation was performed on the tumor. The tumor was encapsulated, so at the time of operation, the microscopic diagnosis was leiomyoma. However, after the operation, the diagnosis was changed to the leiomyosarcoma, because there are many spindle-shaped atypical cells, and many mitoses. We also analyzed the DNA content of the tumor. The DNA index of this tumor was 0.9 and 1.48, therefore, this tumor was DNA aneuploidy. The result of DNA content analysis showed that the tumor is malignant. DNA content analysis is helpful for diagnosis of this kind of sarcoma, because microscopic examination can not readily distinguish benign leiomyoma from malignant leiomyosarcoma. This patient was still alive one year after the operation. Thus, we thought that enucleation of the tumor is a good operational procedure to the leiomyosarcoma of the esophagus, if the tumor is polypoid type and encapsulated. PMID- 8459135 TI - [Minitracheotomy]. AB - Twenty-four consecutive patients undergoing minitracheotomy were reviewed. Postoperative sputum retention was the major indication. In one case the procedure was not possible. Nineteen patients made an uneventful recovery, and decanulation was done in 17. In four patients minitracheotomy treatment was discontinued because formal tracheotomy was performed subsequently. This method is much simpler, less invasive, and more advantageous than formal tracheotomy. It can also be used for the patients after median sternotomy. On the other hand, in the patients with misswallowing because of recurrent nerve palsy etc., conventional tracheotomy should be performed. PMID- 8459136 TI - [Surgical treatment of aberrant right subclavian artery aneurysm]. AB - A 77-year-old female was admitted with dysphagia and back pain. Angiography revealed an aberrant origin of the right subclavian artery from the posterior aspect of the proximal descending thoracic aorta just distal to the origin of the left subclavian artery. The origin of the right subclavian artery was aneurysmal (maximum transverse diameter was 8 cm), and this aneurysm was causing compression of the esophagus. The patient was treated by Teflon patch graft aortoplasty and right subclavian artery reconstruction with the aid of cardiopulmonary bypass and hypothermic selective cerebral perfusion. Postoperative course was uneventful and there were no major complications. PMID- 8459137 TI - [Acute massive pulmonary embolism--report of a case]. AB - A 72-year-old female, who had received medication for hypertension and angina pectoris was hospitalized with complaining of an abrupt dyspnea. Roentgenogram of the chest revealed no abnormal findings except cardiac enlargement. An electrocardiogram showed overloading of the right ventricle. Arterial blood gas analysis of room air showed 55.4 mmHg of PaO2, 25.5 mmHg of PaCO2 and 7.30 of PH, respectively. Acute and massive pulmonary embolism was diagnosed by an emergent pulmonary arteriography. Despite intensive treatment such as infusion of urokinase and heparin for four days, thrombus was still detected in the left main pulmonary artery by a transesophageal echocardiography. By the result of ineffective conservative therapy, embolectomy was performed under cardiopulmonary bypass. However mechanical respiratory support was required for a long time due to the right heart failure, she is doing well for a year after the operation. PMID- 8459138 TI - [An arch and ascending replacement for aortic arch dissection by "separate hypothermia" retrograde cerebral perfusion]. AB - We have developed a new technique of cerebral perfusion during operations on the aortic arch. The concept of this technique is as follows. A retrograde cerebral perfusion provides a relative long time to perform the distal aortic repair, and simplifies the operation. To avoid the disadvantages by deep hypothermia, we perfused from SVC cannula with blood cooled at 10-15 degrees C, from femoral artery with blood cooled at 20-26 degrees C. A successful case using this method is as follows. A 68-year-old man was referred to our hospital for aortic arch dissection. He underwent an operation 4 weeks after onset. Graft replacement of ascending aorta and aortic arch was performed under this method. We perfused blood from SVC cannula at an internal jugular vein pressure of 30 cmH2O, and SVC perfusion flow was 600 cc/min. By this separate hypothermia perfusion, the nasopharyngeal temperature is maintained about 15 degrees C, the rectal temperature is maintained 22-24 degrees C. The duration of cerebral perfusion from SVC cannula was 125 min, but prolonged emergence from anesthesia and neurological deficit were not seen. PMID- 8459139 TI - [Clinical studies on the intercostal minithoracotomy method in spontaneous pneumothorax]. AB - The thirty patients with spontaneous pneumothorax were selected and treated with intercostal minithoracotomy (MT). To study the extent of surgical damage and recurrence rate and total hospital cost in this approach, we compared MT to axillary thoracotomy (AT) with respect to nine variables: (1) operative time (2) feverish period (more than 37 degrees C) (3) total drainage volume for two days after operation (4) white blood cell counts in the 1st postoperative day (POD) (5) CRP in the 3rd POD (6) PSTI (pancreatic secretory trypsin inhibitor) in the 3rd POD (7) period of hospital stay after operation (8) total hospital cost (9) postoperative recurrence rate. A control group of twenty patients undergoing AT over the same period was selected. The average length of operation (recorded in minutes) in the MT group was 25 (SD +/- 10) as compared to 41 (SD +/- 12) in the AT group. The difference between two groups proved to be statistically significant (p < 0.005). The average volume of drainage after operation (recorded in ml) in the MT group was 51 (SD +/- 45) versus 114 (SD +/- 93) in the AT group (p < 0.025). The average period of postoperative fever (recorded in days) in the MT group was 2.6 (SD +/- 1.2) versus 3.6 (SD +/- 1.6) in the AT group (p < 0.01). The average value of WBC (recorded in counts/mm2) in the MT group was 10,955 (SD +/- 2,564) versus 9,966 (SD +/- 3,034) in the AT group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8459140 TI - [A case of mitral regurgitation treated by combined superior transseptal approach and electrophysiological examination of the sinus node function]. AB - A 67-year-old man with mitral regurgitation underwent mitral valvoplasty and annuloplasty successfully. Combined superior transseptal approach was adopted to expose the mitral valve, because the left atrium was small. The exposure of the mitral valve was excellent. But this approach cannot avoid damaging the sinus node artery, so that why the sinus node function was examined electrophysiologically before and after the operation. Sino-atrial conduction time (SACT) and corrected sinus node recovery time (CSRT) were measured as the indices of the sinus node function. Both SNCT and CSRT after the operation was within normal range. As far as this case, combined superior transseptal approach, which gave good exposure of the mitral valve but needed to cut the sinus node artery, did not deteriorate the sinus node function. PMID- 8459141 TI - [The effect of Ryanodine for the myocardial protection in the working heart model of rabbit]. AB - The purpose of this paper is to evaluate the effects of Ryanodine for myocardial protection. Twenty-four rabbits were studied using the working heart model divided four groups. The first is control group with no Ryanodine, the second is 10(-9) M, the third is 10(-8) M and the last one is 10(-7) M Ryanodine with GIK cardioplegic solution respectively. The hemodynamics was studied and the elemental concentrations (Ca, Mg, K, Na, Cl) of myocardial cell was measured using X-ray microanalysis. The results showed that intracellular Ca accumulation was dose-dependently suppressed with Ryanodine during reperfusion and also Ryanodine was significantly effective to maintain the hemodynamics during same one. PMID- 8459142 TI - [Late surgical results of operation in partial atrioventricular canal defect]. AB - Twenty-three patients underwent repair of a partial atrioventricular canal defect and have been followed for a mean of 9.4 years. The patients were divided into two groups according to the management of mitral cleft. Mitral cleft was not repaired in seven patients and directly sutured or repaired by valvuloplasty using pericardium in sixteen patients. In seven patients untreated mitral cleft left, two patients have required mitral valve replacement because of progressive severe mitral regurgitation. In sixteen patients mitral cleft repaired, no patients have required re-operation. However, one patient using pericardium in valvuloplasty, mitral regurgitation was in progress recently due to calcification and degeneration of the pericardium. The peak flow velocity, pressure gradient, pressure half time, and valve area in the mitral valve were measured by echo doppler study. We recognized no statistical difference among two groups about hemodynamic performance in the mitral valve. IN CONCLUSION: 1) As concerns post operative mitral regurgitation, the mitral cleft should be repaired. 2) After mitral cleft closure, the mitral flow pattern was not disturbed. 3) Autologous pericardium should not be adapted for valvuloplasty, because calcification and degeneration of the pericardium may cause progressive incompetency of the mitral valve. PMID- 8459143 TI - [Clinical evaluation of cervical and superior mediastinal lymph node dissection for intrathoracic esophageal carcinoma]. AB - From 1985 to 1989, 257 cases of carcinoma of the thoracic esophagus underwent esophagectomy and lymph node dissection with right thoracotomy based on preoperative staging. Bilateral cervical lymph node dissection was selected in cases in which preoperative examinations (CT, US, EUS, etc) revealed metastasis to cervical or superior mediastinal lymph nodes and cervical or superior mediastinal lymph nodes and in cases of tumors of the upper intrathoracic esophagus. All cases were classified into 3 groups according to region of lymph node dissection. In addition to dissection of the lymph node in the mediastinum and abdomen, group A (102 cases) underwent bilateral cervical and extensive superior mediastinal lymph node dissection (en bloc removal of tissue from the upper mediastinum), group B (61 cases) underwent extensive superior mediastinal lymph node dissection with or without left side cervical dissection and group C (94 cases) underwent standard dissection. Group A contained more advanced cases and cases with metastasis to the upper mediastinal lymph nodes compared to groups B and C. Postoperative complications were also more frequent in group A than groups B or C and were slightly more frequent in group C than group B. Recurrent nerve palsy was recognized in 21% of group A cases. Operative death (within 30 days) was highest in the group A (5.8%) particularly in the elderly group aged over 70 y or absolutely non-curatively resected cases, while in group C the operative mortality was 2.2%. Apart from absolutely non-curatively resected cases, there was no significant difference in the survival curves of the 3 groups, and there was no difference between group A and B cases with no cervical metastasis and group C cases. Also, this selection showed a favorable survival curve following esophagectomy in the period since 1985 compared to the earlier period (1980-1984), excluding absolutely non-curative cases and early stage cases (ep, mm cancer). The results suggest our evaluation methods and selection criteria were appropriate. All absolutely non-curatively resected cases had poor survival rates without significant difference among the 3 groups. In this category of cases, bilateral cervical lymph node dissection of absolutely non curative cases was not effective. In cases with 1-3 metastatic lymph nodes of all, there was a significant difference in prognosis between group A and groups B and C, but there was no significant difference in cases with more than 4 metastatic lymph nodes. Those results suggest that when 1-3 lymph nodes are metastatic, it is necessary to dissect bilateral cervical lymph nodes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8459144 TI - [Postoperative arrhythmia after operation of esophageal cancer]. AB - The postoperative arrhythmias (exclusive of sinus tachycardia) was reviewed in 77 patients (male: 69, female: 8, mean age: 63.9 years) who underwent esophagectomy for esophageal carcinoma. The results were as follows: 1. The incidence of postoperative arrhythmias in all patients but seven who had preoperative chronic atrial fibrillation (af) or pacemaker rhythm was 47.1%, and af was observed most frequently (45.5%). Postoperative arrhythmias occurred in patients with abnormal preoperative electrocardiographic findings more often than in those with normal preoperative electrocardiographic findings (53% vs 41%). The incidence of postoperative arrhythmias in aged patients (> or = 66 years old) was significantly higher than that in younger patients (< or = 65 years old) (64% vs 35%, p < 0.05). Other risk factors for postoperative arrhythmias were sex and history of hypertension. 2. Postoperative arrhythmias occurred more often in patients who underwent blunt dissection of the thoracic esophagus and reconstruction using the whole stomach via the posterior mediastinal route than in those who underwent esophagectomy with right thoracotomy and reconstruction using the gastric tube via the poststernal route (60.0% vs 45.0%). 3. Most supraventricular premature contractions and ventricular premature contractions occurred immediately after surgery or on the first postoperative day, and af often occurred during the first postoperative night or the second postoperative day. 4. For treatment, various antiarrhythmic agents were administered according to the patient's condition. Glucose-insulin-kalium therapy was especially effective (63%). None of the arrhythmias was fatal. PMID- 8459145 TI - [The study of neuropsychological alterations following coronary artery bypass operation as predicted by computed tomography scan of the brain]. AB - The objective of this clinical study is to provide information regarding the association between coexistent cerebrovascular disease and neuropsychological abnormalities after coronary artery bypass operations. Computed tomography scan of the brain was performed in 104 patients pre-operatively, and their post operative neuropsychological functions were evaluated. The patients were categorized as follows according to the CT findings: Seventy-three patients showed normal or slight cerebral cortical atrophy which usually seen in patients over fifty of age (group A). Sixteen showed moderate or severe cortical atrophy (group B). Fifteen patients demonstrated the characteristic findings of Binswanger type; severe white matter hypodensity especially in frontal horns and dilated ventricles (group C). Overt neuropsychological dysfunction was not observed in patient in groups A and B. Six patients in group C showed a combination of dementia, bizarre behavior, disorientation and gait dyspraxia following bypass operations. The pseudobulbar signs were also found in 3 patients. These clinical abnormalities persisted for six days to three weeks, and were most often reversible. Although the underlying mechanism of these deleterious alterations is not elucidated, the ischemic nature of the characteristic white matter lesions was highly suspected. The arteriosclerotic changes of the arteriole of the cerebral cortex and hypoperfusion during cardio pulmonary bypass were supposed to be responsible. Therefore it was concluded that special attention should be focused on neurological evaluation for bypass surgery in group C patients. PMID- 8459146 TI - [Surgical management of tetralogy of Fallot with absent pulmonary valve in infancy]. AB - Between November, 1987 and May, 1990, definitive operation was performed in 7 infants for tetralogy of Fallot with absent pulmonary valve. Preoperative respiratory failure was serious in 5 patients and semi-emergency operation was done. Surgical procedure consisted of closure of ventricular septal defect, reconstruction of right ventricular outflow tract using heterograft valved pericardial roll and plication of aneurysmally dilated pulmonary artery with or without pulmonary artery suspension in 5 infants with severe respiratory distress and heart failure, operated on 26 days to 5 months of age. In the other two less symptomatic infants, operated on at 13 months of age, reconstruction of right ventricular outflow tract was performed by transannular bovine pericardial patch with monocusp. There were no operative death and six infants are doing well 6 months to 3 years postoperatively, but one patient died of prolonged respiratory infection and respiratory failure one year after operation. Postoperative pulmonary arteriogram revealed a 42 to 61 (mean 54) percent reduction in right and left pulmonary artery size in 3 patients who underwent extensive plication of pulmonary artery. We suggest that definitive plication with or without suspension of pulmonary artery, together with closure of ventricular septal defect and reconstruction of right ventricular outflow tract is supposed to eliminate air way obstruction. PMID- 8459147 TI - [Experimental procedure for evaluation of myocardial protection using cultured cardiac myocyte--functional and biochemical effects of hypothermic preservation]. AB - The purpose of the present study was to evaluate the functional and biochemical effects on cardiac myocytes cultured under hypothermic conditions. Cardiac myocytes were isolated from neonatal rat ventricles by collagenase dispersion and cultured for 4 days with MCDB 107 medium containing 2% FCS. Thereafter, the myocytes (12.5 x 10(5) myocytes/culture flask) were incubated at 4 degrees C for 6, 12, 18, 24, 36 or 48 hours. After each incubation, CPK and LDH were measured. The myocytes were then cultured for additional 24 hours at 37 degrees C to evaluate the recovery of myocyte beating rate. The recovery ratio of myocyte beating rate was well maintained at 6 and 12 hours (94.5, 103.4 percent of control: ie, beating rate prior to hypothermic incubation, respectively). Thereafter, the recovery ratio significantly decreased at 18 hours (58.4 percent, p < 0.05), and reached null levels at 48 hours. Release of CPK and LDH increased significantly at 18 hours (CPK: 131.8 mIU/flask, p < 0.05; LDH: 356.0 mIU/flask, p < 0.05), and showed a marked increase at 48 hours (CPK: 961.3, LDH: 1729.5). In addition, the CPK and LDH levels did not significantly increased at 37 degrees C for 48 hours compared to those for 6 hours (6 hours: 7.95, 193.7; 48 hours: 13.5, 199.4, respectively). In summery, 4 degrees C hypothermia induced the myocyte injury both functionally and biochemically, which increased with an increasing incubation time. In addition, it was suggested that an optimal temperature in hypothermic preservation might be 10 degrees C. Thus, this cell-culture system may provide a useful and simple method for in vitro evaluation of hypothermic preservation. PMID- 8459148 TI - [Effects of superoxide dismutase administered by coronary sinus retroperfusion on ischemic reperfused canine heart]. AB - The efficacy of superoxide dismutase administered using synchronized coronary venous retroperfusion (SRP) on the extent of myocardial reperfusion injury was studied. Eighteen mongrel dogs were divided into three groups. A control group (group A) consisting of six dogs was subjected to 90 minutes of acute myocardial ischemia via balloon occlusion of the left anterior descending coronary artery (LAD) followed by 6 hours of reperfusion following abrupt deflation of the balloon. In the second group (group B) consisting of six dogs, the LAD was occluded for 2 hours followed by 5.5 hours of reperfusion. In this group, SRP was applied for 30 minutes prior to full reperfusion. In the third group (group C) consisting of six dogs, balloon inflation and deflation was performed in the same manner as group B except the administration of 10 mg/kg of superoxide dismutase (SOD) using SRP. During the occlusion of LAD, severe ischemia was detected by blood flow measurement using color microsphere in all groups. After reperfusion regional blood flow expressed as the percent of preocclusion value in the subendocardial area in three groups were 25% (group A), 38% (group B) and 76% (group C), respectively. There were significant differences between the groups (p < 0.05). Left ventricular function was assessed as global ejection fraction. Although occlusion of the LAD resulted in a reduction of the left ventricular ejection fraction with a similar magnitude in all groups (A; 37 +/- 5%, B; 32 +/- 7%, C; 58 +/- 10%), there was an improvement in groups B and C during reperfusion (p < 0.05). Infarct size was assessed by triphenyl tetrazolium chloride staining.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8459149 TI - [Esophageal carcinoma with right aortic arch associated with a vascular ring--a case report]. AB - A 56-year-old man with cancer of the mid-thoracic portion of the esophagus and who had a right aortic arch associated with a vascular ring, underwent esophagectomy and mediastinal lymphadenectomy successfully. A routine chest roentgenogram had revealed the right aortic arch. The entire thoracic esophagus was excised via a left thoracotomy, and the left subclavian artery, which originated from a diverticulum of the right descending aorta was located on the left side of the esophagus, ascending from its posterior aspect. The left subclavian artery and the left arterial duct formed a vascular ring which was interrupted by dividing the arterial duct. Histologically, the resected specimen showed poorly differentiated squamous cell carcinoma of the protruding type, and was classified as stage IV, a2, ly(+), V(-) and na(+). Successful mediastinal lymphadenectomy requires that the surgeon pay careful attention to vascular abnormalities, as well as the pathways of the vagal and recurrent nerves. PMID- 8459150 TI - [A case of superior vena cava syndrome caused by adenocarcinoma of the mediastinum--the significance of pulsed Doppler echocardiography in the SVC reconstruction]. AB - We report a case of SVC syndrome caused by adenocarcinoma of the mediastinum, in which brachiocephalic vein flow was recorded by pulsed Doppler echocardiography before and after the SVC reconstruction. A 46-year-old man was admitted to the hospital with the chief complaints of edema of the face and the upper extremities. Although chest X-ray film showed no abnormalities, chest CT and SVC graph demonstrated the obstruction of SVC and bilateral brachiocephalic veins. It was found that bilateral brachiocephalic vein flow displayed characteristic one peak shaped pattern and the peak flow velocity was decreased. We removed SVC and bilateral brachiocephalic veins with the surrounding tissue, and SVC and tributaries were reconstructed with 10 mm ringed ePTFE grafts. Histological examination revealed carcinoma cell infiltration in the wall of SVC. Postoperative phlebography showed well patent grafts, and bilateral brachiocephalic vein flow pattern normalized and the peak flow velocity remarkably increased. PMID- 8459151 TI - [A case of acute hemorrhagic gangrenous acalculous cholecystitis with bile peritonitis during anti-coagulant therapy after coronary-artery bypass grafting]. AB - Acute acalculous cholecystitis is a relatively rare complication occurring after surgery on organs other than the bile duct system. It is often misinterpreted to be a post-operative symptom, and can progress into a very serious condition with high risk of mortality if gangrene and perforation develop. Its occurrence after open heart surgery is relatively rare. We experienced a case of acute hemorrhagic, gangrenous acalculous cholecystitis that developed after coronary artery bypass grafting. The patient, a 78-year-old man, complained post operatively of a right upper abdominal pain. The diagnosis of acute gangrenous acalculous cholecystitis was established on the basis of abdominal sonography and CT, and emergency operation performed was successful. Etiological factors in this case may have included post-operative stasis of bile, swelling of the gallbladder, hypotension during cardiopulmonary bypass, and post-operative anti coagulant therapy administered after open heart surgery. These factors induced intracystic hemorrhage followed by sudden exacerbation, which resulted in gangrenous cholecystitis followed by perforative biliary peritonitis. PMID- 8459152 TI - [A successful case report of coronary artery bypass grafting with aortic no touch technique for the severely calcified ascending aorta]. AB - Calcification of the ascending aorta may render aortic cross-clamping dangerous and aorta-coronary artery bypass grafting impossible. Coronary artery bypass grafting in a 72-year-old woman with drug resistant unstable angina and severely calcified ascending aorta owing to aortitis was successfully performed with aortic no touch technique which consisted of utilization of the left internal thoracic artery, fibrillatory arrest without aortic cross-clamping, left ventricular venting, and femoral artery perfusion. Her postoperative course was uneventful, and she is relieved of angina. PMID- 8459153 TI - [Extensive bowel infarction caused by intraaortic balloon pumping]. AB - Two cases of an extensive bowel infarction occurred during Intraaortic Balloon Pumping (IABP) are reported. In the first, an acute myocardial infarction was seen suddenly on the seventh postoperative day following arterial reconstruction of the right lower leg and his condition required IABP support. Five day after beginning of IABP, severe symptoms suggesting peritonitis appeared, and laparotomy revealed an extensive infarction of small bowel and sigmoid colon. In the second, the patient required IABP support for weaning from cardiopulmonary bypass after completion of coronary artery bypass grafting. A severe peritonitis was caused by an extensive infarction of small and large intestine during two days of IABP support. Cholesterol emboli were found in the small bowel arteries of the case 1 at microscopic examinations of the autopsy specimen. Both patients died of cardiopulmonary failure and renal failure respectively, though necrotic intestine were resected. Circulatory support using IABP should not be selected, when a patient has severe arteriosclerotic lesions of the aorta. PMID- 8459154 TI - [Thoracoscopic resection of pleural tumor]. AB - A thoracoscopic operation was safely performed for a case of a intrathoracic tumor. The patient was a 68-year-old male who had been treated for bronchial asthma and recurrent pneumonia. The reason for a successful operation were one lung-ventilation under general anesthesia, the thoracoscopic electrocautery, the thoracoscopic ultrasonic surgical aspiration system, and thoracoscopic hemoclips. Pathologically the tumor was a benign mesothelioma. The patient was discharged without complications. In the treatment of intrathoracic benign diseases, thoracoscopic surgery is thought to be particularly useful to patients who are at high-risk in conventional thoracic operations due to accompanying respiratory diseases, as well as to patients requiring incisions as small as possible. PMID- 8459155 TI - [A case of malignant duodenal lymphoma following aplastic anemia]. PMID- 8459156 TI - [A case of idiopathic pneumoperitoneum]. PMID- 8459157 TI - [A case of adult rheumatic fever with acute progressive mitral valve diseases]. PMID- 8459158 TI - [A case of repeated pyoderma gangrenosum with myelodysplastic syndrome]. PMID- 8459159 TI - [A case of peripheral facial nerve paralysis with varicella]. PMID- 8459160 TI - [Clinical application of artificial pulmonary surfactants]. PMID- 8459161 TI - [Etiological mechanism of headache]. PMID- 8459162 TI - [Physiopathology of migraine]. PMID- 8459163 TI - [Physiopathology of headache due to muscle contraction]. PMID- 8459164 TI - [Pharmacology of anti-migraine drugs]. PMID- 8459165 TI - [Classification of headache]. PMID- 8459166 TI - [Differential diagnosis of patients with headache]. PMID- 8459167 TI - [Diagnosis and therapy of headache due to subarachnoid hemorrhage]. PMID- 8459168 TI - [Diagnosis and therapy of headache due to chronic subdural hematoma]. PMID- 8459169 TI - [Diagnosis and therapy of headache due to meningitis]. PMID- 8459170 TI - [Diagnosis and therapy in patients with headache due to brain tumor]. PMID- 8459171 TI - [Diagnosis and therapy of trigeminal neuralgia]. PMID- 8459172 TI - [Epidemiology of headache]. PMID- 8459173 TI - [Diagnosis and therapy in patients with headache (discussion)]. PMID- 8459174 TI - Metastatic pigmented neuroectodermal tumor with cranial CT-pathology correlation. AB - Pigmented neuroectodermal tumors are a relatively rare clinicopathologic entity, presenting in a variety of locations. Their histogenesis suggests a transformation from common pleuripotential neural crest cells with varying degrees of differentiation to neural elements and melanocytes. We present a case of just such a tumor, which presented initially in the mandible of a leukemic patient who received irradiation to the skull base, as well as systemic chemotherapy, for suspected cranial leukemic involvement. Subsequent development of intracranial spread was documented both by imaging and pathology. Extracranial spread was also found at autopsy. This unusual presentation and widespread dissemination of the neuroectodermal tumor in our case confirms its aggressiveness and potential for multifocality. PMID- 8459175 TI - ECG of the month. Friend or foe? Non-sinus atrial rhythm. PMID- 8459176 TI - Evaluation and management of chronic aspiration. AB - In managing the patient with chronic aspiration, physicians must have an understanding of normal swallowing physiology as well as swallowing pathology and laryngeal incompetence induced by neurologic, anatomic, and postsurgical insults. We herein review these concepts, and elaborate upon techniques used in evaluation and surgical management of patients exhibiting significant and potentially life threatening aspiration events. PMID- 8459177 TI - Leiomyosarcoma of the spermatic cord. AB - A case of leiomyosarcoma of the spermatic cord occurring in a 62-year-old man is reported. The English literature on the topic is briefly reviewed. PMID- 8459178 TI - Clinical implications of HIV seroprevalence in childbearing women: the Louisiana experience. AB - An epidemiologic analysis of the HIV Seroprevalence Survey of Childbearing Women in Louisiana and the Louisiana AIDS Surveillance Report was conducted to inform health care practitioners of the trends in HIV infection and AIDS cases in women and children. HIV seropositivity in childbearing women has increased by 64% from 1988 to 1991 with an overall rate of 0.15% (202,178 tested). The rate in Orleans Parish is 0.53% (22,833 tested). Louisiana pediatric AIDS cases have increased yearly with 85% due to perinatal transmission. Assuming a 30% perinatal transmission rate, approximately 93 children are expected to develop AIDS in Louisiana within the next few years. Because of anticipated larger numbers of pediatric AIDS cases, health care providers for women and children need to identify their HIV infected patients so that early intervention can begin. PMID- 8459179 TI - Fraud and abuse--could this be you? PMID- 8459180 TI - Managed care, managed competition ... managed concern. PMID- 8459181 TI - Hospital risk management: when bad things happen. PMID- 8459182 TI - Could your practice use a physician extender? PMID- 8459183 TI - Consent to treatment--questions frequently asked. PMID- 8459185 TI - Revisions in the 1993 Medicare RBRVS fee schedule. PMID- 8459184 TI - Managed care in Georgia: a market assessment. PMID- 8459186 TI - Endothelin stimulates testosterone secretion by rat Leydig cells. AB - The present study was designed to evaluate the effects of endothelin (ET) on rat testicular steroidogenesis in vitro and the involvement of prostaglandins (PG) and extracellular calcium in its mechanism of action. To this purpose we examined the effects of ET-1 and ET-3 on basal testosterone secretion, the influence of ET 1 on PGE2 release, the interaction of ET-1 and ET-3 with human chorionic gonadotrophin (hCG) and the interference of indomethacin (an inhibitor of cyclooxygenase) and nifedipine (a calcium-channel blocker) in purified rat Leydig cells. The data indicate that ET-1 and ET-3 stimulate basal and hCG-induced testosterone production although the effects of ET-3 were less marked. In addition, a concomitant release of PGE2 was observed after exposure to ET-1. A synergistic interaction between ET-1 and hCG in stimulating testicular steroidogenesis was revealed. Indomethacin was ineffective in modifying ET-1 evoked testosterone output, while in the presence of nifedipine the stimulatory effect of ET-1 was completely abolished. Since it has been shown by others that ET-1 is produced by rat Sertoli cells and specific binding sites are present in Leydig cells, the results of our study indicate that such a peptide may be regarded as a new paracrine factor able to influence steroidogenesis in Leydig cells. The action of ET-1 requires the activity of voltage-operated Ca2+ channels, while PGE2 activation is not essential for its steroidogenic effect. PMID- 8459187 TI - Beta-endorphin in sows during late pregnancy: effects of cloprostenol and oxytocin on plasma concentrations of beta-endorphin in the jugular and uterine veins. AB - Beta-endorphin was measured in the plasma of pigs during late pregnancy and at different stages of the oestrous cycle. In pregnant animals, beta-endorphin secretion from uteroplacental tissues into the maternal circulation and the possible effects of oxytocin and the prostaglandin F2 alpha (PGF2 alpha) analogue cloprostenol on beta-endorphin release were determined. Plasma beta-endorphin concentrations in pregnant sows were significantly higher than in non-pregnant pigs. However, there were no significant changes in beta-endorphin values throughout the oestrous cycle. Because the increase in plasma beta-endorphin concentrations had occurred before luteolysis and onset of labour it could not be attributed to the stress of parturition. The surgical intervention of a laparotomy increased beta-endorphin release into peripheral plasma. Cloprostenol but not oxytocin caused an immediate increase in plasma beta-endorphin concentrations. At parturition, endogenous PGF2 alpha may be involved in the regulation of beta-endorphin secretion. Concentrations of beta-endorphin in the jugular and uterine vein plasma were not significantly different, and so it would appear that beta-endorphin in the plasma of pregnant sows is not of uteroplacental origin. In conclusion, changes in the concentration of beta endorphin in peripheral plasma, associated with pregnancy but not the oestrous cycle, exist in pigs. Hence a physiological function of peripheral opioid peptides in the periparturient sow is feasible. PMID- 8459188 TI - Follicular development and ovarian hormone secretion following passive immunization of ewes against inhibin or oestradiol. AB - Immunization against inhibin or oestradiol causes an increase in the peripheral plasma concentration of FSH. In this study we have investigated the effect of this post-immunization rise in FSH concentration on follicular development by means of real-time ultrasonography, in ewes in which an ovary and its vascular pedicle had been autotransplanted to a site in the neck. Groups of ewes on day 10 of the luteal phase of the oestrous cycle were injected with a single 10 ml i.v. bolus of plasma from normal ewes (control; n = 4), antiserum to the 1-26 peptide fragment of the N-terminus of the alpha chain of porcine inhibin (n = 5) or antiserum to oestradiol-17 beta (n = 4). The plasma concentration of FSH was unaffected by treatment in the control group but showed a significant (P < 0.001) rise following treatment in both immunized groups (inhibin-immunized 175% over 19h; oestradiol-immunized 138% over 22 h as a per cent of the original value). This rise in FSH concentration was accompanied by a significant (P < 0.001) rise in the total number of follicles > 2.0 mm per ovary in both immunized groups (inhibin-immunized 5.5 +/- 1.0 to 13.6 +/- 1.4; oestradiol-immunized 4.6 +/- 0.5 to 11.5 +/- 1.0).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8459189 TI - FSH and testosterone, alone or in combination, initiate testicular growth and increase the number of spermatogonia and Sertoli cells in a juvenile non-human primate (Macaca mulatta). AB - The present study was designed to investigate the relative contributions of FSH and testosterone in the initiation of testicular growth and function in primates. Four groups (n = 4/group) of juvenile rhesus monkeys (Macaca mulatta), 12-18 months old, were treated with vehicle, a highly purified human FSH preparation (hFSH; Fertinorm, 3 IU/kg per day), testosterone (testosterone enanthate, 125 mg/week) or FSH plus testosterone, for a period of 12 weeks. Compared with vehicle treatment, the administration of hormones significantly (P < 0.05) increased testicular weight and volume, and the diameter of seminiferous tubules. The number of Sertoli cells per tubule cross-section also increased significantly (P < 0.05). Numbers of Ad (dark) spermatogonia (reserve stem cells) were not significantly influenced by any treatment. In contrast, the numbers of Ap (pale) spermatogonia (renewing stem cells) were significantly (P < 0.05) stimulated with hFSH and testosterone alone. Following the combined treatment, numbers of Ap spermatogonia were also higher compared with control but this effect did not attain statistical significance. In half of the animals in both testosterone treated groups, a few prophase I spermatocytes were present. Inhibin concentrations reached adult levels in hFSH-treated groups but remained unaffected by testosterone. Conversely, testosterone failed to influence inhibin levels and, unlike hFSH, increased testicular androgen concentration and epididymal weights. Our observations suggest that hFSH and testosterone alone are capable of initiating testicular growth and gametogenesis in an immature primate. Both hormones probably act via activation of the proliferation of Ap spermatogonia, which are considered to be renewing stem cells within the testis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8459190 TI - Growth hormone (GH) suppression of catecholamine turnover in the chicken hypothalamus: implications for GH autoregulation. AB - GH administered centrally or peripherally inhibits basal or secretagogue-induced GH secretion in domestic fowl. Since the release of pituitary GH is neurally regulated by the hypothalamus, GH autoregulation may be mediated by changes in the content or metabolism of hypothalamic monoamines. When chicken GH (500 micrograms/kg body weight) was injected i.v. into laying hens, tissue catecholamine (adrenaline, noradrenaline and dopamine) concentrations in the preoptic area (POA) and medial basal hypothalamus (MBH) were depleted for 2-24 h, as were concentrations of dihydroxyphenylacetic acid, a dopamine metabolite. The serotonin (5-HT) content of the POA and MBH was unaffected by i.v. GH administration, although a reduction in MBH 5-hydroxyindoleacetic acid suggested a tissue-specific inhibition of 5-HT turnover. Qualitatively similar results were observed in laying hens 24 h after the intracerebroventricular injection of chicken GH (10 micrograms/bird). These results therefore demonstrate aminergic actions of GH within the chicken hypothalamus which may mediate GH autoregulation. However, as amine metabolism is not only suppressed when endogenous GH secretion is reduced, but also at times when normal GH secretion is restored, these aminergic effects may also reflect other actions of GH on central function. PMID- 8459191 TI - Transcription of prolactin gene in milk secretory cells of the rat mammary gland. AB - In-situ hybridization and Northern blot hybridization were used to identify mRNA for pituitary prolactin in mammary tissue obtained from female rats 1 day before expected parturition, 1 day after parturition and on day 7 of lactation. Prolactin cDNA was labelled with 32P for Northern analysis and with digoxigenin for in-situ hybridization. Total and poly(A)+ RNA from pituitary, mammary and control (fat and kidney) tissues were analysed by agarose gel electrophoresis with transfer to nitrocellulose and hybridization to a cDNA for rat prolactin. Although present in much smaller amounts than the 1.0 kb transcript in pituitary RNA homogenates, mammary RNA homogenates from all three stages contained mRNA of approximately 1.0 kb which hybridized with the prolactin probe. Similar analyses of fat and kidney failed to reveal any hybridization at the 1.0 kb size. When tissue sections were hybridized to the cDNA probe, specific hybridization was observed in the milk secretory cells of the mammary alveoli and the lactotroph cells of the anterior pituitary, but not in liver cells or in RNAase-treated sections of mammary tissue. In summary, these results demonstrate that milk secretory cells of the rat mammary gland transcribe the gene for prolactin, and they raise the possibility that a primary target tissue for blood-borne prolactin may also synthesize prolactin. PMID- 8459192 TI - Thyroidal regulation of nuclear tri-iodothyronine receptors in the developing rat testis. AB - Previous work has demonstrated that thyroid hormones influence testis development. Specific receptors for tri-iodothyronine (T3) have been demonstrated in Sertoli cells. The aim of the present study was to examine the possible effect of thyroid hormone on its own receptor during pubertal development by evaluating the influence of thyroid status on T3-binding capacity, -binding affinity and receptor occupancy in nuclei isolated from immature rat testes. The binding capacity for T3 of nuclei from rat testis significantly decreased during pubertal development, being 375 +/- 32, 117 +/- 15 and 44 +/- 7 fmol/mg DNA in 7-, 21- and 35-day-old rats respectively, whereas the affinity of binding, as evaluated by the dissociation constant (Kd), did not change. Early induced hypothyroidism significantly affected the time-course of the postnatal decline of nuclear T3 receptors in the testis. At 21 days of age, the binding capacity for T3 in the testis of methimazole-treated rats was significantly higher with respect to euthyroid controls, being 173 +/- 21 and 117 +/- 15 mol/mg DNA respectively, while the Kd was unaffected. T3 replacement therapy completely prevented changes in T3 receptor number induced by hypothyroidism without modifying the Kd. Our results indicate that nuclear T3 receptors in the developing rat testis are modulated by thyroid hormone. PMID- 8459193 TI - Arginine vasopressin-induced natriuresis in the anaesthetized rat: involvement of V1 and V2 receptors. AB - The present study was undertaken to determine the involvement of the two established vasopressin receptor subtypes (V1 and V2) in arginine vasopressin (AVP)-induced natriuresis and also to determine whether changes in mean arterial pressure (MAP) and/or the renally active hormones atrial natriuretic peptide (ANP), angiotensin II (AII) and aldosterone are a prerequisite for the expression of AVP-induced natriuresis. In Sprague-Dawley rats which were anaesthetized with Inactin (5-ethyl-5-(1'-methylpropyl)-2-thiobarbiturate) and infused with 0.077 mol NaCl/l, infusion of 63 fmol AVP/min was found to be natriuretic whereas an approximately equipotent dose of the specific V2 agonist [deamino-cis1,D-Arg8] vasopressin (dDAVP) did not induce natriuresis. The specific V1 antagonist [beta mercapto-beta,beta-cyclopenta-methylene-propionyl1,O-Me- Tyr2,Arg8]-vasopressin when administered prior to infusion of 63 fmol AVP/min did not inhibit AVP induced natriuresis. AVP-induced natriuresis was not accompanied by changes in MAP or in the plasma concentrations of the renally active hormones ANP, AII or aldosterone. These results suggest that neither the V1 nor the V2 receptors subtypes are involved in AVP-induced natriuresis. In addition, it was found that changes in MAP, plasma ANP, AII or aldosterone concentrations were not a prerequisite for AVP-induced natriuresis. PMID- 8459194 TI - Lack of long-term beta-cell glucotoxicity in vitro in pancreatic islets isolated from two mouse strains (C57BL/6J; C57BL/KsJ) with different sensitivities of the beta-cells to hyperglycaemia in vivo. AB - Previous studies have shown that 4 weeks after syngeneic transplantation of a suboptimal number of islets into either C57BL/6J (BL/6J) or C57BL/KsJ (BL/KsJ) diabetic mice there is an impaired insulin secretion by the perfused grafts. After normalization of the blood glucose level with a second islet graft, the BL/6J strain showed restored insulin secretion whilst that of the BL/KsJ strain remained impaired. The aim of the present work was to study the effects of glucose on the in-vitro function of islet beta-cells from these two mouse strains, with different sensitivities of their beta-cells to glucose in vivo. Isolated pancreatic islets from each strain were kept for 1 week in tissue culture at 5.6, 11, 28 or 56 mmol glucose/l and were subsequently analysed with regard to insulin release, (pro)-insulin and total protein biosynthesis, insulin, DNA and insulin mRNA contents and glucose metabolism. Islets from both strains cultured at 28 or 56 mmol glucose/l showed an increased accumulation of insulin in the culture medium and an enhanced glucose-stimulated insulin release compared with corresponding control islets cultured at 11 mmol glucose/l. After culture at either 5.6 or 56 mmol/l, rates of (pro)insulin biosynthesis were decreased in BL/KsJ islets in short-term incubations at 17 mmol glucose/l, whereas islets cultured at 56 mmol glucose/l showed a marked increase at 1.7 mmol glucose/l. In BL/6J islets, the (pro)insulin biosynthesis rates were similar to those of the BL/KsJ islets with one exception, namely that no decrease was observed at 56 mmol glucose/l. Islets of both strains showed a decreased insulin content after culture with 56 mmol glucose/l.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8459195 TI - Receptor binding of insulin-like growth factor-I to mammary microsomes from non pregnant, pregnant and lactating sheep. AB - Sucrose density centrifugation was used to prepare a partially purified membrane fraction from the mammary glands of non-pregnant, pregnant and lactating sheep. The binding of 125I-labelled insulin-like growth factor-I (IGF-I) was dependent on membrane protein concentration, pH, time and temperature. The binding showed the characteristics of a type-1 IGF receptor, being displaced by IGF-I (median effective dose (ED50) 0.55 nmol/l), less effectively by IGF-II (ED50 8.8 nmol/l) and least effectively by insulin. Glucagon, ovine prolactin and ovine placental lactogen could not displace binding. A molecular weight of 135,000 was determined by affinity cross-linking using disuccinimidyl suberate; this was consistent with the reported size of the type-1 receptor alpha-subunit. Scatchard analysis was used to determine binding affinity and numbers of IGF-I-binding sites. A single class of high-affinity binding sites was found in all physiological states. In non-pregnant sheep and sheep at days 40, 75 and 110-120 of pregnancy and at term, the binding affinity was similar (apparent dissociation constant (Kd) 2.73 +/- 0.31 nmol/l, n = 22). In lactating sheep (weeks 1, 4 and 10), the binding affinity was significantly (P = 0.02) higher (Kd 0.77 +/- 0.06 nmol/l n = 9). Binding capacity was similar in non-pregnant and pregnant sheep (1005 +/- 113 fmol/mg, n = 19), but fell by parturition and remained low in lactation (570 +/- 52 fmol/mg membrane protein, n = 12). The results suggest that the mammary growth of pregnancy is not regulated at the level of the type-1 IGF receptor. PMID- 8459196 TI - Variations in oxytocin secretion during the 4-day oestrous cycle of the rat. AB - Oxytocin concentrations in the plasma, pituitary and hypothalamus of female rats were determined in the morning and evening over the 4-day oestrous cycle. Vasopressin concentrations were also determined to allow calculation of the ratios of the two hormones. The results were compared with those from male rats. Plasma oxytocin concentrations were significantly higher in the evening than in the morning on the day of oestrus. Although the evening concentration achieved was similar on each day of the cycle, morning plasma oxytocin concentrations showed a progressive rise from oestrus to pro-oestrus so that no significant diurnal increases were observed on the other days of the cycle. Vasopressin concentrations in the plasma were also seen to increase over the days of oestrus, dioestrus day 1 and dioestrus day 2. On pro-oestrus the plasma concentrations of vasopressin remained unchanged. The ratio of oxytocin:vasopressin fell during the light hours of the cycle. The hypothalamic content of both hormones showed a rise during the hours of daylight parallel to that seen in the plasma, whereas the pituitary content fell over the same period. The diurnal pattern of hormone release observed in male rats was similar to that in females at oestrus. However, the plasma oxytocin concentrations were significantly higher in the male. The plasma clearance rate of vasopressin did not vary significantly during the oestrous cycle. However, the plasma clearance rate for oxytocin did show significant variation, being highest on dioestrus day 1 and lowest on dioestrus day 2. PMID- 8459197 TI - The regulation of oxidative drug metabolism by growth hormone in the dwarf goat: differences from and similarities to the mechanisms in rats. AB - The effects of bovine GH (BST), administered in different dose patterns, on in vivo oxidative drug metabolism, were studied in female dwarf goats. Animals received recombinantly derived methionyl BST at a dose of 500 micrograms/kg body weight per 24 h for 6 days. It was administered to one group of goats as one s.c. injection per day, another group received a similar 24-h dose divided into three s.c. injections given at 8-h intervals, and the third group received 50 micrograms BST/kg body weight every 2.5 h by a pulsative i.v. infusion. Oxidative metabolic capacity was assessed by determining plasma sulphadimidine (SDD) elimination and urinary metabolite excretion. SDD shows a marked sex-dependent plasma elimination in dwarf goats, with male goats having a lower plasma clearance than female goats. When BST was given by daily injection, no clear effects on SDD plasma clearance or urinary metabolite excretion were observed. However, when the total dose was divided into three injections given at 8-h intervals, the plasma SDD elimination rate decreased. This was associated with a decrease in urinary excretion of the two main hydroxy SDD metabolites. When BST was given by discontinuous i.v. infusion, simulating the male endogenous plasma GH pattern, a marked decrease in SDD plasma clearance was observed. In addition, the excretion of the two urinary hydroxy metabolites was considerably reduced. These results suggest that GH can affect drug oxidation in dwarf goats via mechanisms similar to those suggested for rats. However, in the dwarf goat, the sex differences in drug metabolism are opposite to those in rats. PMID- 8459198 TI - The effect of free fatty acids on the in-vitro binding of testosterone in human plasma. AB - The effect of supraphysiological levels of free fatty acids (FFA) on the binding of testosterone to sex-hormone binding globulin (SHBG) and on non-SHBG binding in both male plasma and plasma from pregnant women was studied. Six FFAs were added to plasma as individual acids. No alteration in testosterone binding to SHBG could be demonstrated with any of the FFAs in either male plasma or plasma from pregnant women. When the same plasma was heated to destroy SHBG binding, a highly significant (P < 0.01) increase in non-SHBG binding was seen in both male plasma and plasma from pregnant women when the unsaturated FFAs oleic, linoleic and linolenic acids were added. No significant difference was demonstrated with the saturated FFAs, palmitic, stearic and arachidic acids. PMID- 8459199 TI - Short-term endocrine consequences of total body irradiation and bone marrow transplantation in children treated for leukemia. AB - We studied 24-h hormone profiles and hormonal responses to insulin-induced hypoglycaemia prospectively in 23 children of similar age and pubertal stage, nine of whom had received prior cranial irradiation (group 1) and fourteen of whom had not (group 2), before and 6-12 months after total body irradiation (TBI) for bone marrow transplantation in leukaemia. Fourier transformation demonstrated that group 1 children had a faster periodicity of GH secretion before TBI than group 2 children (160 vs 200 min) but the amplitude of their GH peaks was similar. There were no differences between the groups in circadian cortisol rhythm, serum concentrations of insulin-like growth factor-I (IGF-I), sex steroids and basal thyroxine (T4). The peak serum GH concentrations observed after insulin-induced hypoglycaemia were similar between the two groups but the majority of patients had blunted responses. TBI increased the periodicity of GH secretion in both groups (group 1 vs group 2; 140 vs 180 min), but the tendency to attenuation of amplitude was not significant. There were no significant changes in the peak serum GH concentration response to insulin-induced hypoglycaemia which remained blunted. Serum IGF-I, sex steroid, cortisol or T4 concentrations were unchanged. Low-dose cranial irradiation has an effect on GH secretion affecting predominantly frequency modulation leading to fast frequency, normal amplitude GH pulsatility. This change is accentuated by TBI. In patients with leukemia, there is a marked discordance between the peak serum GH response to insulin-induced hypoglycaemia compared with the release of GH during 24-h studies, irrespective of the therapeutic regimen used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8459200 TI - The effect of basic fibroblast growth factor on the growth and function of human thyrocytes. AB - Basic fibroblast growth factor (bFGF) was quantitated in human primary thyrocyte cultures and thyroid cell lines produced by transfection with pSV3neo. Immunoreactive-bFGF (ir-bFGF) bound to heparin-Sepharose affinity columns eluted with 1.8-2.0 mol NaCl/l and had a molecular weight of approximately 17,000. Recombinant human bFGF in the presence of 5% serum increased the growth of transfected human thyrocytes but not the growth of primary human thyrocytes. Preincubation of cells with up to 100 micrograms bFGF/l potentiated TSH stimulated cAMP release from the transfected cells but inhibited release from primary human thyroid cultures. bFGF may be an important modulator of thyroid cell function and growth. PMID- 8459201 TI - Receptor editing in self-reactive bone marrow B cells. AB - A central paradigm of immunology is clonal selection: lymphocytes displaying clonally distributed antigen receptors are generated and subsequently selected by antigen for growth or elimination. Here we show that in mice transgenic for anti H-2Kk,b antibody genes, in which a homogeneous clone of developing B cells can be analyzed for the outcome of autoantigen encounter, surface immunoglobulin M+/idiotype+ immature B cells binding to self-antigens in the bone marrow are induced to alter the specificity of their antigen receptors. Transgenic bone marrow B cells encountering membrane-bound Kb or Kk proteins modify their receptors by expressing the V(D)J recombinase activator genes and assembling endogenously encoded immunoglobulin light chain variable genes. This (auto)antigen-directed change in the specificity of newly generated lymphocytes is termed receptor editing. PMID- 8459202 TI - Transforming growth factor beta 1 selectivity stimulates immunoglobulin G2b secretion by lipopolysaccharide-activated murine B cells. AB - Bacterial lipopolysaccharide (LPS) has been reported to induce immunoglobulin (Ig)G2b class switching, yet we observed strain differences in IgG2b secretion in response to this mitogen. Specifically, BALB/c B cells, unlike those from DBA/2, synthesized relatively low amounts of IgG2b relative to IgG3, IgG1, or IgM. This report demonstrates that transforming growth factor (TGF) beta 1, previously shown to induce IgA class switching, selectively stimulates IgG2b secretion by BALB/c resting B cells activated with LPS. This activity was specifically reversed with a neutralizing anti-TGF-beta 1 antibody. The ability of TGF-beta 1 to act directly on highly purified membrane (m)IgM+ mIgG2b- cells to stimulate IgG2b production, stimulate an increase in IgG2b-secreting cells, and selectively increase the steady-state levels of germline gamma 2b RNA, suggests that it promotes IgG2b class switching. In this regard, addition of anti-TGF-beta antibody to cultures of DBA/2-derived resting B cells activated by LPS, alone, led to selective reduction in IgG2b secretion, indicating that endogenous TGF beta 1 accounts for the high IgG2b secretory response observed in that strain. Finally, TGF-beta 1 failed to stimulate IgG2b secretion by B cells activated with dextran-conjugated anti-IgD antibody. We propose that TGF-beta 1 is a switch factor for the murine IgG2b subclass for appropriately activated B cells. In combination with other data, this would show that all six non-IgM, non-IgD isotypes in the mouse can be selectively induced by specific cytokines. PMID- 8459203 TI - Phenotypic and functional analysis of positive selection in the gamma/delta T cell lineage. AB - Recent evidence suggests that T cells expressing gamma/delta antigen receptors (T cell receptor [TCR]) are subject to positive selection during development. We have shown that T cells expressing a class I major histocompatibility complex (MHC)-specific gamma/delta TCR transgene (tg) are not positively selected in class I MHC-deficient, beta 2-microglobulin (beta 2m) gene knockout mice (tg+ beta 2m-). In this report, we examine phenotypic and functional parameters of gamma/delta positive selection in this transgenic model system. TCR-gamma/delta tg+ thymocytes of mature surface phenotype (heat stable antigen-, CD5hi) were found in beta 2m+ but not in beta 2m- mice. Moreover, subsets of tg+ thymocytes with the phenotype of activated T cells (interleukin [IL]2R+, CD44hi, or Mel 14lo) were also present only in the beta 2m+ mice. Cyclosporine A, which blocks positive selection of TCR-alpha/beta T cells, also inhibited gamma/delta tg+ T cell development. These results support the idea that positive selection of TCR gamma/delta requires active TCR-mediated signal transduction. Whereas tg+ beta 2m+ thymocytes produced IL-2 and proliferated when stimulated by alloantigen, TCR engagement of tg+ beta 2m- thymocytes by antigen induced IL-2R expression but was uncoupled from the signal transduction pathway leading to IL-2 production and autocrine proliferation. Overall, these results demonstrate significant parallels between gamma/delta and alpha/beta lineage development, and suggest a general role for TCR signaling in thymic maturation. PMID- 8459204 TI - Functional characterization of a signal transducing motif present in the T cell antigen receptor zeta chain. AB - A conserved sequence motif has been identified in a number of signaling subunits associated with hematopoietic cell antigen receptors. Here, we characterize signaling by a 17 amino acid motif that is triplicated in the T cell antigen receptor zeta chain. Analysis of zeta truncations and constructs containing the isolated motif demonstrates that this motif is sufficient for the induction of both proximal and distal events associated with T cell activation. Stimulation of truncations that contain either one, two, or three copies of the motif results in induction of an identical pattern of tyrosine phosphoproteins. Moreover, triplication of the NH2-terminal zeta motif results in enhanced signaling, suggesting a redundant role in signal amplification for the three motifs in zeta. Finally, we demonstrate the association of a recently identified protein tyrosine kinase ZAP-70 with this motif, and provide evidence for its involvement in zeta function. PMID- 8459206 TI - Regulation of hematopoiesis in vitro by alloreactive natural killer cell clones. AB - Natural killer (NK) cells lyse autologous and allogeneic target cells even in the absence of major histocompatibility complex (MHC) class I antigens on the target cells. Recently, however, human allospecific NK cell clones have been generated that recognize at least five distinct specificities inherited recessively and controlled by genes linked to the MHC. Because the genetic specificity of these alloreactive NK cells in vitro appears analogous to that of in vivo NK cell mediated murine hybrid resistance, i.e., the rejection of parental bone marrow in irradiated F1 animals, we tested the ability of human alloreactive NK clones to recognize allogeneic hematopoietic progenitor cells. NK cells from two specificity 1 alloreactive NK clones, ES9 and ES10, significantly and often completely suppressed colony formation by purified peripheral blood hematopoietic progenitor cells from specificity 1-susceptible donors, but had no significant effect on the cells of specificity 1-resistant donors. Activated polyclonal NK cells were less efficient than the NK clones in inhibiting colony formation and had a similar effect on cells from both specificity 1-susceptible and -resistant donors. The alloreactive NK clones produced cytokines with a suppressive effect on in vitro hematopoiesis, such as interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha), when exposed to phytohemagglutinin blasts from specificity 1-susceptible, but not -resistant donors. However, the mechanism by which alloreactive NK cells inhibit colony formation is more consistent with a direct cytotoxic effect than with the production of inhibitory cytokines because antibodies (anti-IFN-gamma, alpha-TNF-alpha, and -lymphotoxin) that completely blocked the inhibition by polyclonal NK cells had only a minimal effect on the inhibition by the alloreactive clones. Moreover, the alloreactive clones were directly cytolytic in a 51Cr release assay against enriched preparations of peripheral blood progenitor cells from specificity 1-susceptible donors. These data indicate that the alloreactive NK cells are likely the human counterpart of the cells mediating murine hybrid resistance and that these cells might play clinically important roles in rejection or in graft-versus-leukemia reactions after allogeneic bone marrow transplantation. PMID- 8459205 TI - Molecular characterization of the humoral responses to Cryptococcus neoformans infection and glucuronoxylomannan-tetanus toxoid conjugate immunization. AB - The molecular characteristics of the humoral immune response to a serotype A Cryptococcus neoformans infection were compared with the response elicited by a cryptococcal glucuronoxylomannan-tetanus toxoid (GXM-TT) conjugate. Anticryptococcal monoclonal antibodies (mAbs) isolated from both responses have previously been shown to recognize the same antigenic determinant of cryptococcal GXM. Southern blot and sequence analyses indicate that the hybridomas isolated from each response arose from only a few precursor B cells. All the mAbs generated from the infected and GXM-TT conjugate-immunized mice utilize the same VH7183 family member: JH2/JH4, v kappa 5.1, and J kappa 1; mAbs generated by different B cells had complementarity-determining region 3's (CDR3s) composed of seven amino acids with a common sequence motif. Thus, the molecular analysis of these anticryptococcal mAb-producing hybridomas indicated that the response to both cryptococcal infection and conjugate immunization was oligoclonal and highly restricted with regard to immunoglobulin gene utilization. The GXM-TT conjugate primarily stimulated isotype switching and clonal proliferation, and did not result in hybridomas expressing additional immunoglobulin repertoires. The mAbs from both responses had a number of replacement mutations at the 5' end of CDR2 that appear to be the result of antigen-driven selection. Somatic mutation also resulted in altered epitope specificity for one mAb, 13F1. Passive administration of representative mAbs from different clones generated in response to the GXM-TT conjugate prolonged survival of lethally infected mice. PMID- 8459207 TI - Regression of bladder tumors in mice treated with interleukin 2 gene-modified tumor cells. AB - This study explored the use of interleukin 2 (IL-2) and interferon gamma (IFN gamma) gene-modified tumor cells as cellular vaccines for the treatment of bladder cancer. The mouse MBT-2 tumor used is an excellent model for human bladder cancer. This carcinogen-induced tumor of bladder origin resembles human bladder cancer in its etiology and histology, and responds to treatment in a manner similar to its human counterpart. Using retroviral vectors, the human IL-2 and mouse IFN-gamma genes were introduced and expressed in MBT-2 cells. The tumor forming capacity of the cytokine gene-modified MBT-2 cells was significantly impaired, since no tumors formed in mice injected intradermally with either IL-2- or IFN-gamma-secreting cells, using cell doses far exceeding the minimal tumorigenic dose of parental MBT-2 cells. Furthermore, mice that rejected the IL 2- or IFN-gamma-secreting tumor cells became highly resistant to a subsequent challenge with parental MBT-2 cells, but not to 38C13 cells, a B cell lymphoma of the same genetic background. To approximate the conditions as closely as possible to the conditions prevailing in the cancer patient, inactivated cytokine secreting cells were used to treat animals bearing tumors established by orthotopic implantation of MBT-2 cells into the bladder wall of the animal. Treatment of mice carrying a significant tumor burden with IL-2-secreting MBT-2 cells had a significant inhibitory effect on tumor progression with extended survival. Moreover, in 60% of the mice the tumor regressed completely and the animals remained alive and free of detectable tumor for the duration of the observation period. Treatment of tumor-bearing animals with IL-2-secreting MBT-2 cells was superior to the use of cisplatin, a chemotherapeutic agent used in the treatment of bladder cancer. The therapeutic effect of IFN-gamma-secreting cells was minimal and treatment with unmodified MBT-2 cells had no effect on tumor growth or survival, showing that the parental MBT-2 cells were nonimmunogenic in this experimental setting. Most importantly, mice that exhibited complete tumor regression after treatment with IL-2-secreting MBT-2 cells became resistant to a subsequent challenge with a highly tumorigenic dose of parental MBT-2 cells, indicating that long-term immunological memory was established in the "cured" mice. PMID- 8459208 TI - Resident macrophages (ramified microglia) of the adult brown Norway rat central nervous system are constitutively major histocompatibility complex class II positive. AB - A flow cytometric phenotype for isolated adult central nervous system (CNS) ramified microglia was previously defined (CD45low CD11b/c+) in the Lewis strain rat, that clearly distinguished these cells from all blood-derived leucocytes, the latter being CD45high. Consistent with the reported lack of major histocompatibility complex (MHC) expression in the CNS, isolated microglia were mostly MHC class II-. Employing these phenotypic criteria, we now show that a proportion of microglia in Brown Norway (BN) strain rats are constitutively MHC class II+. In spinal cord, up to 25% of microglia are distinctly positive and most have some level of expression. In situ staining of MHC class II+ microglial cells in BN rats indicates that positive cells are typical of ramified microglia on the grounds of both morphological appearance and anatomical location. In Lewis (LEW) rats, the few MHC class II-expressing cells isolated from the normal CNS are CD45high blood-derived cells and not resident microglia. After infection of both LEW and BN rats with a neurotropic murine hepatitis virus (MHV-JHM), MHC class II was rapidly upregulated on microglia in the BN but not in the LEW strain. In the latter, inflammatory cells were the predominant MHC class II expressing population. Nevertheless, most microglia in the LEW strain could, after some delay, be induced to express MHC class II after transfer of an experimental autoimmune encephalomyelitis (EAE)-inducing encephalitogenic T cell line. Paradoxically, strains resistant to EAE (exemplified by the BN) contained more constitutive MHC class II-expressing microglia than susceptible ones, when a variety of strains were examined. The results clearly establish that the normal CNS may contain MHC class II-expressing cells that are a resident rather than a transient blood-derived population. It is significant that this expression is strain related, but there is no evidence that microglial cell constitutive MHC class II expression predisposes to EAE susceptibility. PMID- 8459209 TI - Thymus epithelium induces tissue-specific tolerance. AB - Most current models of T cell development include a positive selection step in the thymus that occurs when T cells interact with thymic epithelium and a negative selection step after encounters with bone marrow-derived cells. We show here that developing T cells are tolerized when they recognize antigens expressed by thymic epithelium, that the tolerance is tissue specific, and that it can occur by deletion of the reactive T cells. PMID- 8459210 TI - B lymphocytes may escape tolerance by revising their antigen receptors. AB - To explore mechanisms that prevent autoreactivity in nonautoimmune mice, endogenous immunoglobulin (Ig) light (L) chains that associate with a transgenic anti-DNA heavy chain were analyzed. The antibodies from splenic B cell hybridomas of such mice did not bind double-stranded DNA (dsDNA) and their L chain sequences showed a biased use of V kappa and J kappa gene segments. The 44 L chains in this survey were coded for by just 18 germline genes. Six of the genes, each belonging to a different V kappa group, were used more than once and accounted for three fourths of all sequences. Based on the distribution of V kappa genes, the L chain repertoire in this line of transgenic mice was estimated at 37 V kappa genes. The most frequently observed gene, a member of the V kappa 12/13 group, was identified in 16 hybrids. In addition, the majority of V kappa genes used J kappa 5. We interpret the skewed representation of V kappa and J kappa gene segments to result from negative selection. Based on the data, we suggest that V kappa rearrangements giving rise to anti-dsDNA reactivity are removed from the repertoire by a corrective mechanism capable of editing self-reactive Ig. PMID- 8459211 TI - T cells expressing specific V beta elements regulate immunoglobulin E production and airways responsiveness in vivo. AB - The role of T cells expressing specific V beta elements was examined in the regulation of allergen-specific immunoglobulin (Ig)E production and airways responsiveness (AR). In BALB/c mice, inhalation of the allergen ovalbumin (OVA) induced an IgE anti-OVA response, immediate cutaneous reactivity, and increased AR. These results were associated with an expansion of V beta 8.1/8.2 T cells in local draining lymph nodes of the airways and the lung. Transfer of V beta 8.1/8.2 T cells from sensitized mice stimulated an IgE anti-OVA response, immediate cutaneous hypersensitivity, and increased AR in naive syngeneic recipients. In contrast, OVA-reactive V beta 2 T cells inhibited these effects. These data demonstrate for the first time that T cells with different V beta specificities play a critical role in the in vivo regulation of allergen-specific IgE production and AR. PMID- 8459212 TI - Human antibodies reactive with beta-amyloid protein in Alzheimer's disease. AB - Four human B cell lines established by Epstein-Barr viral transformation of B cells from a patient with a clinical diagnosis of Alzheimer's disease (AD) were found to secrete antibodies that react with plaques and cerebrovascular blood vessels in AD brain in a staining profile characteristic of beta-amyloid protein (beta-AP) in AD brain. Two of these antibodies were shown to be reactive with a rare plaque in a normal brain. In these studies, immunofluorescence and avidin biotin complex immunoperoxidase methodology were used to determine antibody reaction, and thioflavine S was used to double label amyloid and neurofibrillary tangles. The four antibodies also reacted with neurons in normal and AD brain. Absorption studies, dot immunoblots, and enzyme-linked immunosorbent assays with beta-amyloid peptides 1-28 (beta-A1-28) and 1-40 (beta-A1-40) indicate the major determinant of the reactive epitope is located in the region of amino acids 1-28 of beta-AP. However, inhibition studies demonstrate a significant contribution to the antigenic determinant by the 29-40 region of the beta-A1-40. These antibodies represent the first human autoantibodies against beta-AP. The pathological significance of these autoantibodies is discussed. PMID- 8459213 TI - Cloning and expression of intercellular adhesion molecule 3 reveals strong homology to other immunoglobulin family counter-receptors for lymphocyte function associated antigen 1. AB - Based on protein sequence, we have isolated a cDNA for intercellular adhesion molecule 3 (ICAM-3), the most recently defined counter-receptor for lymphocyte function-associated antigen 1 (LFA-1). Expression of the cDNA yields a product that reacts with monoclonal antibody to ICAM-3 and functions as a ligand for LFA 1. The deduced 518-amino acid sequence of the predicted mature protein defines a highly glycosylated type I integral membrane protein with five immunoglobulin (Ig)-like domains. The five Ig-like domains of ICAM-3 are highly homologous with those of human ICAM-1 (52% identity) and human ICAM-2 (37% identity). PMID- 8459214 TI - Lethal exacerbation of Pneumocystis carinii pneumonia in severe combined immunodeficiency mice after infection by pneumonia virus of mice. AB - Mice homozygous for the mutant allele scid (severe combined immunodeficiency) have been described as excellent models for Pneumocystis carinii (Pc) pneumonia (PCP), a major health problem in patients with acquired immune deficiency syndrome (AIDS) and other immunodeficiency states. Other microorganisms have been shown to infect AIDS patients simultaneously with Pc, but whether one opportunist is able to directly influence the pathogenicity of another has not been determined previously. We have deliberately coinfected scid mice (with extent Pc infection) with a variety of primarily pneumotropic viruses and bacteria and have identified pneumonia virus of mice as causing a dramatic increase in the density of Pc organisms and the morbidity due to PCP in immunodeficient scid mice. This finding has clinical significance in the management of PCP, in that the identification and treatment of coinfecting pneumotropic pathogens may be as important as treatment targeted at Pc. A search for other synergistic (or antagonistic) microorganisms and determination of their mechanism(s) of action in altering the progression of PCP is indicated. PMID- 8459215 TI - Interleukin 10 protects mice from lethal endotoxemia. AB - Interleukin 10 (IL-10) decreases production of IL-1, IL-6, and tumor necrosis factor alpha (TNF-alpha) in vitro, and neutralization of IL-10 in mice leads to elevation of the same monokines. We test here whether this monokine-suppressing property of IL-10 confers on it the capacity to protect mice from lipopolysaccharide-induced shock, a monokine-mediated inflammatory reaction. A single injection of 0.5-1 microgram of recombinant murine IL-10 reproducibly protected BALB/c mice from a lethal intraperitoneal injection of endotoxin. This result was obtained whether the IL-10 was administered concurrently with, or 30 min after the injection of endotoxin. The protective effect of IL-10 was reversed by prior injection of neutralizing anti-IL-10 antibodies, and correlated with a substantial decrease in endotoxin-induced TNF-alpha release. These data implicate IL-10 as a candidate for treatment of bacterial sepsis, and more generally as an effective antiinflammatory reagent. PMID- 8459216 TI - T cell-dependent induction of NF-kappa B in B cells. AB - In comparison to B cell stimulation mediated by surface immunoglobulin (Ig) antigen receptor ligation, little is known about the intracellular events associated with T cell-dependent B cell responses. A model for the efferent phase of T cell-B cell interaction was used to examine the capacity of activated T cells to trigger nuclear expression of the trans-acting transcription factor, NF kappa B, in B cells. Fixed, activated, but not fixed, resting Th2 cells were found to induce increased binding activity for a kappa B site-containing oligonucleotide in a time-dependent manner. This induction of NF-kappa B was eliminated by an antibody directed against a 39-kD cell interaction protein on activated T cells as well as by a soluble form of B cell CD40. Of particular relevance to intracellular signaling, NF-kappa B induction was not diminished by prior depletion of B cell protein kinase C (PKC) with phorbol myristate acetate. These results strongly suggest that T cell-dependent B cell stimulation is associated with NF-kappa B induction via p39-CD40 interaction and that this is brought about by non-PKC dependent signaling, in marked contrast to the previously documented requirement for PKC in sIg receptor-mediated stimulation. This suggest that NF-kappa B responds to more than one receptor-mediated intracellular signaling pathway in B cells and may be part of a "final common pathway" for B cell stimulation. PMID- 8459217 TI - Thymic T cell anergy in autoimmune nonobese diabetic mice is mediated by deficient T cell receptor regulation of the pathway of p21ras activation. AB - Thymic T cell anergy, as manifested by thymocyte proliferative unresponsiveness to antigens expressed in the thymic environment, is commonly believed to mediate the acquisition of immunological self-tolerance. However, we previously found that thymic T cell anergy may lead to the breakdown of tolerance and predispose to autoimmunity in nonobese diabetic (NOD) mice. Here, we show that NOD thymic T cell anergy, as revealed by proliferative unresponsiveness in vitro after stimulation through the T cell receptor (TCR), is associated with defective TCR mediated signal transduction along the PKC/p21ras/p42mapk pathway of T cell activation. PKC activity is reduced in NOD thymocytes. Activation of p21ras is deficient in quiescent and stimulated NOD T cells, and this is correlated with a significant reduction in the tyrosine phosphorylation of p42mapk, a serine/threonine kinase active downstream of p21ras. Treatment of NOD T cells with a phorbol ester not only enhances their p21ras activity and p42mapk tyrosine phosphorylation but also restores their proliferative responsiveness. Since p42mapk activity is required for progression through to S phase of the cell cycle, our data suggest that reduced tyrosine phosphorylation of p42mapk in stimulated NOD T cells may abrogate its activity and elicit the proliferative unresponsiveness of these cells. PMID- 8459218 TI - High-frequency representation of a single VH gene in the expressed human B cell repertoire. PMID- 8459219 TI - The life span of naive alpha/beta T cells in secondary lymphoid organs. AB - We have determined the life span of naive CD4-8+ T cells in T cell receptor transgenic mice. We find that such cells do not divide in secondary lymphoid organs in both normal euthymic mice and T cell-deficient mice. By both continuous labeling and by chasing pulse-labeled cells, we find that the minimum life span of the naive T cells is in the order of 8 wk. PMID- 8459220 TI - Activated human lymphocytes and aggressive non-Hodgkin's lymphomas express a homologue of the rat metastasis-associated variant of CD44. AB - A recently described splice variant of CD44 expressed in metastasizing cell lines of rat tumors, has been shown to confer metastatic potential to nonmetastasizing rat pancreatic carcinoma and sarcoma cell lines. Using antibodies raised against a bacterial fusion protein encoded by variant CD44 sequences, we have explored the expression of variant CD44 glycoproteins on human lymphoid cells and tissues and on non-Hodgkin's lymphomas. Normal lymphohematopoietic cells express barely detectable low levels of variant CD44 glycoproteins, whereas T lymphocytes, upon activation by mitogen or antigen, transiently upregulate expression of specific CD44 variant glycoproteins. The reaction pattern of various antibodies indicates that these CD44 variants contain the domain encoded by exon v6, which is part of the variant that in the rat confers metastatic capability. It is interesting that overexpression of v6 was also found in several aggressive, but not low-grade, non Hodgkin's lymphomas. PMID- 8459222 TI - A rat CD4 mutant containing the gp120-binding site mediates human immunodeficiency virus type 1 infection. AB - CD4 is the primary receptor for the human immunodeficiency virus type 1 (HIV-1). Early mutational studies implicated a number of residues of CD4, centered in the region 41-59, in binding to gp120. However, further mutational analyses, together with studies using inhibitory antibodies or CD4-derived peptides, have suggested that other regions of CD4 are also involved in binding or postbinding events during infection. To resolve these ambiguities, we used rat CD4 mutants in which particular regions were replaced with the corresponding sequence of human CD4. We have previously shown that some of these are able to bind HIV-1 gp120, and here we test their ability to act as functional receptors. We find that the presence of human CD4 residues 33-62 is enough to confer efficient receptor function to rat CD4, and we conclude that it is unlikely that regions of CD4 outside this sequence are involved in specific interactions with HIV-1 during either infection or syncytium formation. PMID- 8459221 TI - A requirement for membrane-associated phospholipase A2 in platelet cytotoxicity activated by receptors for immunoglobulin G and complement. AB - Platelets are potent antibody- and complement-dependent cytotoxic effector cells. We showed previously that a single platelet can lyse a target cell sensitized with immunoglobulin G (IgG) and complement components up to C3 (C integral of 3b denotes the target cell-bound fragment of complement up to C3; the precise nature of the bound C3 fragment has not been established), and that the complete cytotoxic system capable of specific recognition and lysis resides in platelet membranes. To define the components of platelet membranes required for cytotoxicity, a set of inhibitors of phospholipase A2 (PLA2) that act by different chemical mechanisms was tested. The lytic reaction is blocked at appropriate concentrations of bromophenacylbromide, mepacrine, and manoalide. When platelets are treated with bromophenacylbromide, inhibition of cytolytic activity and that of PLA2 enzymatic activity occur in parallel. Platelets release arachidonate when incubated with target cells bearing IgG and C integral of 3b, confirming that Fc gamma R and complement receptor trigger both PLA2 action and efficient lysis. Inhibition by thimerosal of a reverse reaction, i.e., reacylation catalyzed by acyltransferase, causes increased target cell lysis, presumably by increasing the products of PLA2 action. Platelet cytotoxicity is increased when platelets are pretreated with some products of PLA2: exogenous lysophospholipids and not free arachidonic acid increase cytotoxicity. Electron microscopy suggests that platelets and target cells may fuse, possibly as a result of the formation of lysophospholipids which are well-known membrane fusogens. Fixation with paraformaldehyde does not affect platelet cytotoxicity, suggesting that the complete cytotoxic system resides as a preformed complex in platelet membranes. The results indicate that platelet membrane-associated PLA2, together with receptors for Fc and complement, are required for platelet cytotoxicity. PMID- 8459223 TI - Genes for interleukin 7 are transcribed in leukemic cell subsets of individuals with chronic lymphocytic leukemia. AB - Regulation of expression of interleukin 7 (IL-7) mRNA is aberrant in the leukemic subset of cells of chronic lymphocytic leukemia (CLL) patients. The entire coding sequence for IL-7 as well as an alternatively spliced IL-7 mRNA are transcribed in these leukemic cells. No IL-7 mRNA expression is detected in fresh peripheral blood mononuclear cells from normal individuals. Furthermore, the "normal" nonleukemic subsets of cells isolated from the same CLL patients also do not express IL-7 mRNA. The only subset of cells in which IL-7 mRNA is detected is the one that contains the leukemic cells themselves. The polymerase chain reaction was used to examine cytokine expression, and flow cytometry was used to purify the various subsets of peripheral blood mononuclear cells examined in these studies, as well as to examine IL-7 receptor expression. A proportion of the cells from the CLL patients express receptors that are capable of binding IL-7, whereas T cell-depleted normal cell preparations do not express receptors for IL 7 that are detectable with IL-7 fluorokines. The IL-7 receptor-bearing cells in CLL patients include a portion of leukemic cells and a fraction of the T cells, as well as some non-T, non-B cells. These findings suggest that IL-7 and IL-7 receptor expression in CLL may be relevant not only to growth regulation of the leukemic cells but to the immunological abnormalities that occur in the disease as well, possibly via the induction of inappropriate immune activity of IL-7 receptor-bearing cells. PMID- 8459224 TI - Site-specific deletions involving the tal-1 and sil genes are restricted to cells of the T cell receptor alpha/beta lineage: T cell receptor delta gene deletion mechanism affects multiple genes. AB - Site-specific deletions in the tal-1 gene are reported to occur in 12-26% of T cell acute lymphoblastic leukemias (T-ALL). So far two main types of tal-1 deletions have been described. Upon analysis of 134 T-ALL we have found two new types of tal-1 deletions. These four types of deletions juxtapose the 5' part of the tal-1 gene to the sil gene promoter, thereby deleting all coding sil exons but leaving the coding tal-1 exons undamaged. The recombination signal sequences (RSS) and fusion regions of the tal-1 deletion breakpoints strongly resemble the RSS and junctional regions of immunoglobulin/T cell receptor (TCR) gene rearrangements, which implies that they are probably caused by the same V(D)J recombinase complex. Analysis of the 134 T-ALL suggested that the occurrence of tal-1 deletions is associated with the CD3 phenotype, because no tal-1 deletions were found in 25 TCR-gamma/delta + T-ALL, whereas 8 of the 69 CD3- T-ALL and 11 of the 40 TCR-alpha/beta + T-ALL contained such a deletion. Careful examination of all TCR genes revealed that tal-1 deletions exclusively occurred in CD3- or CD3+ T-ALL of the alpha/beta lineage with a frequency of 18% in T-ALL with one deleted TCR-delta allele, and a frequency of 34% in T-ALL with TCR-delta gene deletions on both alleles. Therefore, we conclude that alpha/beta lineage commitment of the T-ALL and especially the extent of TCR-delta gene deletions determines the chance of a tal-1 deletion. This suggests that tal-1 deletions are mediated via the same deletion mechanism as TCR-delta gene deletions. PMID- 8459225 TI - Evolutionary conservation of major histocompatibility complex-DR/peptide/T cell interactions in primates. AB - Many major histocompatibility complex (MHC) polymorphisms originate from ancient structures that predate speciation. As a consequence, members of the Mhc-DRB1*03 allelic lineage are not only present in humans but in chimpanzees and rhesus macaques as well. This emphasizes that Mhc-DRB1*03 members must have been present in a common ancestor of these primate species that lived about 30 million years ago. Due to the accumulation of genetic variation, however, alleles of the Mhc DRB1*03 lineage exhibit species-unique sequences. To investigate the biological importance of such conservation and variation, we have studied both the binding and antigen presentation capacity of various trans-species Mhc-DRB1*03 lineage members. Here we show that p3-13 of the 65-kD heat-shock protein (hsp65) of Mycobacterium leprae and M. tuberculosis binds not only to HLA-DR17(3) but also to some chimpanzee and rhesus macaque class II-positive cells. Comparison of the corresponding human, chimpanzee, and rhesus macaque Mhc-DRB1*03 lineage members revealed the presence of uniquely shared amino acid residues, at positions 9-13 and 26-31, of the antigen-binding site that are critical for p3-13 binding. In addition it is shown that several nonhuman primate antigen-presenting cells that bind p3-13 can activate HLA-DR17-restricted T cells. Certain amino acid replacements, however, in Mhc-DRB1*03 lineage members did not influence peptide binding or T cell recognition. Therefore, these studies demonstrate that some polymorphic amino acid residues (motifs) within the antigen-binding site of MHC class II molecules that are crucial for peptide binding and recognition by the T cell receptor have been conserved for over 30 million years. PMID- 8459226 TI - Melanoma cells and normal melanocytes share antigens recognized by HLA-A2 restricted cytotoxic T cell clones from melanoma patients. AB - HLA-A2-restricted, CD3+, CD8+, alpha/beta+ cytotoxic T cell (CTL) clones were isolated from peripheral blood (PBL) or tumor infiltrating lymphocytes (TIL) of two HLA-A2+ melanoma patients (9742 and 5810), to evaluate the possible recognition of autologous melanoma and of allogeneic HLA-A2-matched normal melanocytes. These CTL clones lysed not only fresh and cultured autologous melanoma cells, but also allogeneic HLA-A2+, but not HLA-A2-, normal melanocytes. The lysis of autologous neoplastic cells and of melanocytes could be inhibited by an anti-HLA-A2 monoclonal antibody (mAb). Lysis of the normal melanocytes was not dependent on the presence of human or fetal calf serum in the culture medium. HLA A2-restricted CTL clones recognized not only proliferating melanocytes cultured in complete melanocyte medium, but also melanocytes made quiescent by culture for up to 6 d in a basal medium devoid of exogenous factors such as phorbol ester (O tetradecanoyl phorbol 13-acetate [TPA]), epidermal growth factor, insulin, and pituitary extracts. Analysis of specificity of four CTL clones (A75, A83, A94, and 119) from patient 9742, performed on a panel of 39 targets, indicated that the three HLA-A2-restricted CTL (A75, A83, and A94) lysed all but one of nine allogeneic melanomas expressing the HLA-A2 molecule with no reactivity on nine HLA-A2- allogeneic melanomas. Only a few instances of borderline reactivity were seen by the same effectors on 21 targets of nonmelanocyte lineage, including 12 carcinomas of different histology, four Epstein-Barr virus-transformed B cells (lymphoblastoid cell lines [LCL]), including the autologous LCL, four lines of normal fibroblasts, and normal kidney cells. Lack of reactivity on allogeneic targets of nonmelanocyte lineage occurred in spite of expression of HLA-A2 on 14 of these targets as determined by conventional tissue typing and cytofluorimetric analysis with four different anti-HLA-A2 mAb. These data indicate that tissue related antigens can be expressed on normal and neoplastic cells of the melanocyte lineage and can be recognized in association with HLA-A2 by CTL clones from melanoma patients. PMID- 8459228 TI - Heat flux, oxygen flux, and mitochondrial redox state as a function of oxygen availability and ciliary activity in excised gills of Mytilus edulis. AB - The ciliated gill of bivalve molluscs is situated at an interface between animal and environment. Cilia propel water past the gills to deliver oxygen and nutrition to the animal. Ciliary activity is driven by dynein ATPases and requires a continual supply of ATP at a rate sufficient to match the rate of ATP hydrolysis. Control of the balance between ATP supply and demand in the ciliated gill, and how this balance may be altered by environmental stresses, is unknown. In this pilot study, metabolic flux of excised gills from the marine mussel Mytilus edulis was examined in response to oxygen availability and to serotonin stimulated ciliary activity. Heat flux and oxygen flux were measured simultaneously with calorespirometry. In parallel experiments, the redox state of mitochondrial cytochromes was determined with in vivo spectrophotometry. Above 4 kPa pO2, heat flux was supported by aerobic metabolism. Anoxic heat flux was less than 5% of aerobic heat flux. Heat and oxygen fluxes nearly doubled in gills in the presence of 10 microM serotonin; however, half-maximal pO2 for heat and oxygen fluxes and for reduction of mitochondrial cytochromes remained unchanged from control levels. In gills having inactive cilia in half-strength seawater, half-maximal pO2 for heat and oxygen fluxes and for cytochrome reduction nearly doubled compared with valves in full-strength seawater. These data indicate that limitation to oxygen delivery imposed by boundary layers may be reduced when ciliary beat frequency is elevated, leading to enhanced oxygen flux to intracellular mitochondrial which matches the increased energy demand by the cilia. PMID- 8459227 TI - Receptor editing: an approach by autoreactive B cells to escape tolerance. AB - To determine the fate of anti-DNA antibody-bearing B cells in normal mice, we generated transgenic mice bearing the heavy (H) and light (L) chain genes of a well-characterized anti-double-stranded DNA antibody. This antibody was originally isolated from a diseased MRL/lpr mouse and has characteristics common to spontaneously arising anti-DNA antibodies. Results show that the H/L transgene (tg) immunoglobulin receptor is not expressed by animals bearing both tgs, although single tg animals (H or L) express their transgenes. Young H/L tg animals express few B cells, whereas adult H/L tg animals maintain almost normal B cell numbers. Analysis of the immunoglobulin receptors used by adult B cells shows that all contain the tg H chain in association with endogenous L chains. These B cells transcribe the L tg as well as the rearranged endogenous L chain gene, and loss of endogenous L chain gene transcription results in resurrection of the 3H9 H/L tg product. Examination of the endogenous L chains used by these cells shows that they represent a highly restricted subset of V genes. Taken together, these data suggest that autoreactive transgenic B cells can rearrange endogenous L chain genes to alter surface receptors. Those L chains that compete successfully with the L tg for H chain binding, and that create a nonautoreactive receptor, allow the B cell to escape deletion. We suggest that this receptor editing is a mechanism used by immature autoreactive B cells to escape tolerance. PMID- 8459229 TI - Mesodermal cell adhesion to fibronectin-rich fibrillar extracellular matrix is required for normal Rana pipiens gastrulation. AB - New observations on thin strips of cells from the leading edge of the involuting presumptive mesoderm explanted onto FN-coated substrate show a striking preferential cellular emigration from the leading edge of explants. Microinjected probes (Fab' anti-FN, Fab' anti-integrin and RGD-peptides) that disrupt cell adhesion to the FN-matrix on basal surface of the blastocoel roof also disrupt normal anuran gastrulation, producing blocked embryos with no adhesion of leading edge mesodermal cells to the blastocoel roof, abnormal epiboly, and defects of mesodermal cell spreading across the basal surface of the blastocoel roof toward the animal pole. These results show that the FN-rich fibrillar extracellular matrix on the basal surface of the blastocoel roof is required for normal gastrulation in Rana pipiens embryos. PMID- 8459230 TI - Lack of coupling between onset of giant transformation and genome endoreduplication in the mural trophectoderm of the mouse blastocyst. AB - Prominent among the various types of cell that differentiate from the trophectoderm of the mouse blastocyst are trophoblastic giant cells. Repeated endoreduplication of the genome accompanies the growth of these cells, which have been shown to be polytene rather than polyploid. Early stages in giant transformation have been examined, mainly in the mural trophectoderm of the implanting blastocyst which gives rise to the primary trophoblastic giant cells. One confusing issue is whether these early stages include the onset of endoreduplication of the genome. This issue has been addressed in the present study by comparing the DNA content of nuclei in isolated trophectoderm and ICM tissue rather than, as previously, by relating measurements on air-dry preparations of entire blastocysts to those of adult liver. The results, particularly those from delayed and reactivated blastocysts, show that genome endoreduplication is not an obligatory early event in the transformation of mural trophectoderm cells. PMID- 8459231 TI - Structure of the vaginal plugs generated by normal rats and by rats with partially removed seminal vesicles. AB - Normal male rats generate vaginal plugs that appear to be firmly apposed to the vagino-cervical junction and permit a large number of spermatozoa to reach the uterus. A few spermatozoa form entangled masses inside these plugs, as revealed by light microscopy. Males in which the seminal vesicles have been partially removed produce plugs that are smaller and softer than those generated by normal males, and the plugs display a cup-like structure at the proximal end. The cup like structure is completely filled with spermatozoa that exhibit a characteristic arrangement in relation to the plug material. In this situation, the number of spermatozoa that reach the uterus is very much reduced. Experiments were also carried out to explore the restoration of sperm transport by addition of a vaginal plug. Such experiments involved successive matings of individual females with a seminal vesicle-deprived male and with a vasectomized male (which generated the plug) and also the intravaginal injection of seminal vesicle secretions after mating with a seminal vesicle-deprived male. In none of the experimental situations was transport of spermatozoa to the uterus restored, and the plug consisted of a large quantity of trapped spermatozoa inside a mass of coagulated proteins. The results suggest that the structure of the plug depends on the amount of seminal vesicle secretion present in the ejaculate and that the vaginal plug must be formed immediately after deposition of the sperm if spermatozoa are to reach the uterus. PMID- 8459232 TI - Production and characterization of monoclonal antibodies specific for bovine oviductal glycoproteins. AB - Four monoclonal antibodies (MAbs) were produced in rat cells against materials obtained from the bovine oviduct. The MAbs (1H10, 2A4, 2C5, and 1B12) reacted strongly with the oviductal epithelium of cows in the follicular phase. An immunohistochemical study demonstrated that each of the MAbs bound strongly to the supranuclear cytoplasm of epithelial cells of the oviduct, but not of the stromal cells. Antigens that reacted with the MAbs were characterized by immunoblotting analysis of proteins after fractionation by SDS-PAGE under reducing conditions of oviductal flushings obtained from cows at estrus. All MAbs strongly stained a band of protein with a molecular weight (MW) of 85-97 kD. MAb 1H10 also reacted with the minor band of a 55-kD protein. Similar antigens were not detected in uterine flushings, follicular fluid, and serum. No specific immunohistochemical reactivity with the MAbs was observed with other tissues from the reproductive tract and with nonreproductive tissues. The immunohistochemical reactions were completely eliminated by pretreatment of tissues with trypsin, but not with periodic acid, results that suggest that the antigenic determinants that react with the MAbs were proteinaceous rather than carbohydrate. We have thus established clones that produce 4 MAbs that are specific for oviduct-specific glycoproteins of the cow. PMID- 8459233 TI - C-type natriuretic peptides are potent dilators of shark vascular smooth muscle. AB - Previous studies of the effects of C-type natriuretic peptides (CNP) in intact mammals have demonstrated limited hypotensive responses, in contrast to other natriuretic peptides. Our previous studies, on isolated vascular smooth muscle (VSM) from various fish species, utilizing either mammalian or non-homologous fish atrial natriuretic peptides (ANP), have demonstrated vasodilation with a relatively high sensitivity (EC50 approximately 5 nM). The recent sequencing of a C-type natriuretic peptide from the heart of the dogfish shark, Squalus acanthias, has enabled us to compare the efficacy of this peptide on aortic VSM from that species with two other CNPs (from killifish and pig), as well as rat ANP. The EC50 of dilation for sCNP, as well as kCNP and pCNP, was 0.5 nM, over 15 times lower than the EC50 of the response to rANP. These data suggest that CNP is released from the dogfish shark heart and is a circulating hormone with potent vasodilatory effects, in sharp contrast to the apparent role of CNP predominantly as a brain neuropeptide in mammals. PMID- 8459234 TI - A diel rhythm of the short-circuit current expressed by the opercular epithelium of the killifish, Fundulus heteroclitus. AB - The inner opercular epithelium of the killifish, Fundulus heteroclitus, may be separated as a single epithelial sheet and mounted in an Ussing-style chamber with the short-circuit current (Isc) approximating chloride secretion. Steady state opercular Isc values in seawater-adapted killifish were higher in tissues removed from fish in the afternoon than those observed in the morning. Opercular conductance was also higher in the afternoon than the morning. The opercular steady state Isc from killifish on a 13:11 light:dark cycle exhibited a diel variation with the peak in the middle of the light cycle and a nadir near the end of the dark phase. Temperature and salinity remained constant during the experimental period. Daily variation cued by the photoperiod should be considered when using this preparation as an experimental model for ion transport in the gill of a seawater-adapted fish. PMID- 8459235 TI - The DNA laboratory and neurological practice. PMID- 8459236 TI - Carolus Linnaeus (Carl Linne) 1707-78. PMID- 8459238 TI - A controlled trial of the retraining of the sensory function of the hand in stroke patients. AB - A controlled trial of retraining of the sensory function of the hand was undertaken in hemiplegic patients after the period of spontaneous recovery. Twenty hemiplegic patients with sensory deficit in the hand, two or more years after stroke, received systematic retraining three times a week for six weeks. Sensation in the plegic hand was tested before and after this period in these patients and in 19 untreated control patients. The treated group showed large and significant gains on all sensory tests (P < 0.001), while no change occurred in the control group. It is concluded that somatosensory deficit can be alleviated even years after stroke and that rehabilitation for stroke patients should include sensory retraining for those with sensory deficit. PMID- 8459237 TI - The management of acute visual failure. AB - This review of acute visual failure covers the clinical manifestations and management of ocular strokes CRA occlusion, BRA occlusion and AION. The diagnostic process for each patient requires meticulous attention to: 1. Blood pressure, heart rate and rhythm, palpation of the temporal arteries, and auscultation of the heart, neck, eyes and head. 2. Dilated funduscopic examination. 3. Immediate blood tests: complete blood count, PT, PTT, platelet count, ESR, fibrinogen level, fasting blood sugar, cholesterol, triglyceride and blood lipids. A test for antiphospholipid antibodies (ACLA and LA) is recommended in unexplained cases of CRA occlusion. Non-invasive investigations should utilise a battery of tests: 1. Carotid non-invasive studies; the useful tests give information about the presence of a haemodynamic lesion (Dopper ultrasonography and oculoplethysmography), analyse the bruit to determine the residual lumen diameter (phonoangiography), or image the artery with ultrasound (B-Scan ultrasonography). 2. Two-dimensional echocardiogram Invasive investigations are required in selected patients: 1. A temporal artery biopsy 2. A carotid arteriogram if the patient is a candidate for endarterectomy. The patient can be screened first with a non-invasive MRA of the neck and brain. 3. A timed FFA, particularly in cases of CRA occlusion when occlusion of the ophthalmic artery is suspected, in cases of AION of possible embolic origin or in AION to document the position of the watershed zone of the choroidal circulation and its relation to the optic nerve head. Emergency treatment in CRA occlusion is designed to lower intra-ocular pressure and dislodge the embolus. In impending CRA occlusion heparin is useful. Urgent systemic corticosteroids are needed when CRA occlusion, or AION are due to arteritis. In other situations treatment is directed towards preventing recurrence or involvement of the other eye by reducing or eliminating identified risk factors. PMID- 8459239 TI - Urinary symptoms and the neurological features of bladder dysfunction in multiple sclerosis. AB - One hundred and seventy patients with multiple sclerosis and bladder dysfunction were evaluated. Emphasis was placed on the relationship between their neurological features and urinary symptoms. The severity of the urinary symptoms was related to the degree of pyramidal impairment in the lower limbs so that both problems are thought to reflect the extent of spinal involvement. No other neurological features correlated with bladder dysfunction. Detrusor hyperreflexia was the commonest finding on cystometry and no patient had areflexia. More than half of the patients had a significantly raised post-micturition residual volume but symptoms were largely unreliable in predicting poor bladder emptying. In this series only two patients had evidence of upper tract disease: both men with severe, longstanding neurological disease who had indwelling catheters. Detrusor hyperreflexia can be anticipated in patients with MS who have irritative urinary symptoms and pyramidal signs in their lower limbs. After measurement of the residual volume appropriate treatment can be instituted. PMID- 8459240 TI - Shunting normal pressure hydrocephalus: the predictive value of combined clinical and CT data. AB - The value of an ordinal global scale derived from combined clinical and CT data (clin/CT scale) to predict the clinical outcome in 112 patients shunted for presumed normal pressure hydrocephalus (NPH) was analysed. The clinical data were retrospectively collected, all CT scans were re-evaluated, and the clin/CT scale was determined blind to the results of further ancillary tests and to the post surgical outcome. The scale ranked three classes of prediction: on the basis of clinical and CT characteristics, improvement after shunting was probable, possible, or improbable. The predictive value of the clin/CT scale for the subgroup of communicating NPH was established for two different strategies, depending on the strictness of selection criteria for shunting. In the subgroup of patients with presumed communicating NPH, the prevalence of shunt responsiveness was 29%; the best strategy was to shunt only patients with probable shunt-responsive NPH: the sensitivity was 0.54, the specificity 0.84, and the predictive accuracy 0.75, with a limited number of ineffective shunts (11%) and missed improvements (13%). The study illustrates its need to assess the pre-test probability of NPH based on combined clinical and CT data, before establishing the clinical usefulness of an ancillary test. PMID- 8459241 TI - Calbindin D-28k and parvalbumin immunoreactivity in the frontal cortex in patients with frontal lobe dementia of non-Alzheimer type associated with amyotrophic lateral sclerosis. AB - The morphology and distribution of local-circuit neurons (interneurons) were examined, by calbindin D-28k and parvalbumin immunocytochemistry, in the frontal cortex (area 8) in two patients with frontal lobe dementia of non-Alzheimer type associated with classical amyotrophic lateral sclerosis (ALS), and in seven normal cases. The density of calbindin D-28k immunoreactive cells was dramatically reduced in ALS patients, but the density of parvalbumin immunoreactive neurons was preserved. Decreased density of calbindin D-28k immunoreactive neurons, which are mainly located in the upper cortical layers, may interfere with the normal processing of cortico-cortical connections, whereas integrity of parvalbumin-immunoreactive cells may be associated with the preservation of the major inhibitory intracortical circuits in patients with frontal lobe dementia. PMID- 8459242 TI - Acquired pendular nystagmus in multiple sclerosis: clinical observations and the role of optic neuropathy. AB - Thirty seven patients with pendular nystagmus due to multiple sclerosis were reviewed. Most developed nystagmus later in a progressive phase of the disease. All had cerebellar signs on examination and evidence of optic neuropathy. MRI in eight patients showed cerebellar or brainstem lesions in seven; the most consistent finding was a lesion in the dorsal pontine tegmentum. Dissociated nystagmus was seen in 18 patients: in these the signs of optic neuropathy were often asymmetric and the severity correlated closely with the side with larger oscillations. This suggests that dissociations in acquired pendular nystagmus may be due to asymmetries in optic neuropathy rather than asymmetries in cerebellar or brainstem disease. PMID- 8459243 TI - Chronic thalamic stimulation improves tremor and levodopa induced dyskinesias in Parkinson's disease. AB - Chronic thalamic stimulation was performed in 10 Parkinsonian patients with disabling tremor and poor response to drug therapy. During the stereotactic procedure, an electrode was introduced in the ventralis intermediate nucleus of the thalamus. Test stimulation was performed during the intra-operative procedure and a few days after surgery using an external stimulator. When tremor was obviously reduced by thalamic stimulation, an internal stimulator was implanted under the clavicle. Tremor was initially suppressed in all cases and reappeared whenever stimulation was stopped. Patients were followed for 22 to 34 months. Tremor was controlled in eight cases but reappeared after three months in two cases. Levodopa induced dyskinesias were observed before electrode implantation in 5 cases. They consisted of peak-dose choreic or ballistic dyskinesias in 4 cases and biphasic dystonic dyskinesias in 3 cases. Peak-dose dyskinesias were greatly improved or suppressed in all cases. Biphasic dyskinesias were improved in 2 cases. Thalamic stimulation was well tolerated. Mild dystonic hand posture related to the deep brain stimulation was observed in one case. No neuropsychological side-effects were noted. Thalamic stimulation could prove to be an adequate treatment for resistant tremor and levodopa induced dyskinesias. PMID- 8459244 TI - Unilateral frontal lobectomy can produce strategy application disorder. AB - Following a 5 cm left frontal lobectomy for the removal of a mixed astrocytoma oligodendroglioma, a 51 year old right handed man showed a marked dissociation between his performance on standard neuropsychological tests and his everyday behaviour. In contrast to his intact neuropsychological test performance, he was impaired on a test of "strategy application" which requires goal articulation, plan specification, self-monitoring, and evaluation of outcomes, as well as the establishment of mental "markers" to trigger specific behaviour. Strategy application disorder can therefore be produced by a unilateral circumscribed frontal lobe lesions. PMID- 8459245 TI - Post-ictal psychosis after right temporal lobectomy. AB - Of 298 patients who had temporal lobectomies for intractable epilepsy, 4 (1.3%) developed post-ictal psychosis for the first time after surgery. All were males of normal intelligence with no pre-operative psychiatric disorder. Psychosis followed both complex partial and generalised seizures. The psychotic symptoms showed polymorphic features. Right temporal lobectomy may increase the susceptibility to post-ictal psychosis in patients who are not seizure free after surgery, particularly in the first post-operative year. PMID- 8459246 TI - Magnetic resonance imaging assessment of brainstem distortion associated with a supratentorial mass. AB - Quantitative measurements of brainstem distortion and neural dysfunction were obtained in 25 cases of chronic subdural haematoma. The horizontal and rotational brainstem displacements were measured on axial and coronal MRI in all patients pre-operatively, and brainstem auditory evoked responses (BAERs) were obtained in 11 cases. Logarithmic relationships were noted on both horizontal and rotational displacements of the brainstem and cerebrum. The type of shift changed in the rostro-caudal direction. In the axial plane, the cerebral hemisphere shifts and rotates, the midbrain shifts laterally with no rotation, and the pons shifts minimally but rotates moderately. In the coronal plane, the marked rotation of the cerebral hemisphere and moderate rotation of the brainstem result in midbrain kinking, suggesting a downward displacement of the midbrain. The prolongation of BAER latencies and central conduction times correlated with septum shift. The results of peak-V latency indicated that brainstem rotation in the coronal plane reflects upper brainstem dysfunction most closely. This study presents objective measurements of brainstem displacement shown on MRI, and clarifies the relationships between anatomical and physiological changes in the brainstem that are associated with supratentorial lesions. PMID- 8459247 TI - The execution of bimanual movements in patients with Parkinson's, Huntington's and cerebellar disease. AB - Patients with Parkinson's disease have difficulty in performing two different tasks simultaneously. The present study tested whether this deficit was specific to the disease or was found in other patient groups. An identical pattern of performance was shown by a group of patients with cerebellar disease and, to a lesser extent, by a group of patients with Huntington's disease. Further research should focus on clarifying the nature of the deficits and the reasons for the similar performances in the various patient groups. PMID- 8459248 TI - An epidemiological study of Wilson's disease in the Republic of Ireland. AB - In a population based study of the prevalence of Wilson's disease in the Republic of Ireland from 1970-89, 26 definite and probable cases were ascertained. The adjusted birth incidence rate was 17.0 per million live births (95% (confidence interval 9.9 to 27.2)) for the 20 year period 1950-69. The gene frequency was 0.41% (95% (confidence interval 0.31% to 0.52%) indicating that one in 122 of the population was a gene carrier. Allowing for a maximal degree of consanguinity, the gene frequency is reduced to 0.36% and the proportion of heterozygotes to one in 139 of the population. The consistency of the adjusted birth incidence rates over the decades 1950-59 and 1960-69 suggests a high degree of ascertainment of diagnosed cases of Wilson's disease. PMID- 8459249 TI - Hemianopia, hemianaesthesia, and hemiplegia after right and left hemisphere damage. A hemispheric difference. AB - The incidence of somatosensory, visual half-field and motor deficits contralateral to a hemispheric lesion in a continuous series of 154 left brain damaged and 144 right brain damaged stroke patients were investigated. These contralateral disorders were more frequent after lesions of the right hemisphere. This difference cannot be attributed to a bias in patients' selection. It is suggested that left spatial neglect is the factor underlying this hemispheric difference. PMID- 8459250 TI - Post-ictal Kluver-Bucy syndrome after temporal lobectomy. AB - In both animals and humans, Kluver-Bucy syndrome is produced by bilateral temporal lobectomy. It is characterised by hypersexuality, visual agnosia, strong oral tendencies, dietary changes, and hypermetamorphosis. Recurrent, postictal Kluver-Bucy syndrome occurred transiently after seizures in a female who had undergone unilateral temporal lobectomy. The pathophysiological mechanism may have been postictal dysfunction of the remaining temporal lobe, producing a transient functional bilateral temporal lobectomy. PMID- 8459251 TI - Localised neuronal migration disorder and intractable epilepsy: a prenatal vascular aetiology. AB - Localised neuronal heterotopias are an increasingly recognised cause of intractable focal epilepsies. The aetiology of these circumscribed disorders of neuronal migration is often unknown although in some instances proximity to areas of prenatal infarction suggests that severe ischaemia was responsible. A patient is described with intractable complex partial seizures associated with heterotopic grey matter and cerebral hypoplasia confined to the territory of the left posterior cerebral artery; the left hippocampus was spared. Angiography showed a normal left anterior choroidal artery but a hypoplastic left posterior cerebral artery, implicating prenatal ischaemia without frank infarction as the aetiology of the malformation. PMID- 8459252 TI - Polymyositis with plasma cell infiltrate in essential mixed cryoglobulinaemia. AB - A patient with essential cryoglobulinaemia who presented with polymyositis is described. Muscle biopsy showed intense plasma cell infiltration of muscle. Plasmapheresis produced a rapid resolution of the cutaneous manifestations of the disease, but little improvement in muscle strength. Oral steroids resulted in moderate improvement in muscle strength. There have been no previously reported cases of polymyositis in association with essential cryoglobulinaemia. PMID- 8459253 TI - Confirmation of clinical diagnosis in requests for prenatal prediction of SMA type I. AB - The recent discovery of a major SMA-locus in the chromosomal region 5q makes it possible to carry out prenatal DNA studies in families in which a child with SMA type I has been born. Since direct mutation analysis is not yet possible, the reliability of prenatal prediction of SMA type I usually depends on the certainty of the clinical diagnosis in the index patient. Sixteen requests were received for DNA studies in couples who had had a previous child with SMA type I. After re evaluation, the performance of prenatal diagnosis was rejected in four cases. Among the other twelve families prenatal DNA analysis of chorion villus biopsies has been carried out in three families. In all three cases the fetus had inherited the high-risk haplotypes from both parents, and the parents chose to terminate the pregnancy. An illustration of the prenatal DNA studies in one family is given. The importance of confirmation of the diagnosis SMA type I before performing DNA studies is emphasised. PMID- 8459254 TI - A case of music imperception. PMID- 8459255 TI - Fregoli delusion and erotomania. PMID- 8459256 TI - Bilateral crossed optic ataxia in a corpus callosum lesion. PMID- 8459257 TI - Cost-effective investigations of patients with suspected TIAs. PMID- 8459258 TI - Comparison of the antibacterial activity and synergistic activity towards antibiotics of different mammalian sera. AB - The antibacterial activity against Escherichia coli ATCC 10798 and Staphylococcus aureus Mag 90 of normal sera from nine species of mammals was investigated by Avantage (Abbott). Human and rat sera showed the highest antibacterial activity against E. coli ATCC 10798, while all investigated sera did not exhibit, till the maximum concentration tested (20%), spontaneous antibacterial activity against S. aureus Mag 90. Heat inactivated sera (56 degrees C for 30 min) of all investigated species lost their antibacterial activity, but maintained their synergistic effect with sub-MICs of some antibacterial drugs, principally against E. coli ATCC 10798. PMID- 8459259 TI - Transferable resistance to imipenem in hospital isolates of Pseudomonas aeruginosa. AB - We monitored systematically, for more than five years, the eventual transferability of resistance to imipenem in strains of Pseudomonas aeruginosa isolated from patients in Frankfurt University Clinics. Quite recently, four strains have been found which transfer resistance to imipenem to recipient strains of P. aeruginosa. Although in three strains imipenem was the only antibiotic where resistance was transferred directly, the indirect selection analysis showed that, in each instance, determinants of resistance to carbenicillin and kanamycin were co-transferred. The situation in the fourth strain was more complicated. It was resistant to at least ten antipseudomonad antibiotics, and transferred directly not only determinants of resistance to imipenem, but also to carbenicillin and kanamycin, as did the other strains, plus determinants of resistance to ceftazidime and cefotaxime. The origin and mode of spread of resistance determinants in studied strains is briefly discussed. PMID- 8459260 TI - Trends in gram-positive bloodstream organism resistance: a seven-year audit of five glycopeptides and other drugs at a large university hospital. AB - Gram-positive pathogens (n = 525) isolated from bloodstream infections were tested by a reference broth microdilution method to establish antibiotic susceptibility trends (1985 to 1991). Cefazolin, ciprofloxacin, gentamicin, novobiocin, oxacillin, rifampin, teicoplanin, vancomycin, trimethoprim/sulfamethoxazole, daptomycin and two investigational glycopeptides (LY264826 and MDL62873) were investigated. Strains were selected without bias (first two isolates each month/species; no patient duplicates) as follows: 132 Staphylococcus aureus, 129 Staphylococcus epidermidis, 72 Staphylococcus haemolyticus, 130 Enterococcus faecalis and 62 other enterococci. All isolates were susceptible to vancomycin and teicoplanin except for Staphylococcus haemolyticus which had a resistant teicoplanin MIC90 of 64 micrograms/mL. The susceptibilities to vancomycin and teicoplanin were unchanged over the monitored period. Daptomycin, LY264826 and MDL62873 also demonstrated consistent activity; MDL62873 being superior with a MIC90 of 0.12 micrograms/mL. In 1990-1991 a significantly increased resistance to ciprofloxacin was observed among oxacillin resistant strains of staphylococci. Our data suggest that the emergence of invasive vancomycin-resistant strains in Gram-positive isolates remains a rare phenomenon. However, we have experienced an emergence of numerous ciprofloxacin resistant strains among staphylococci that precludes its empirical use at our institution. PMID- 8459261 TI - Teicoplanin with other drugs: possible pharmacological interactions. AB - The contemporaneous employment of two or more drugs may present the risk of modifying the required therapeutic effect or producing adverse reactions. These interactions are of a pharmacokinetic and pharmacodynamic type. Teicoplanin is an antibiotic with a glycopeptide structure, produced by Actinoplanes teichomyceticus, active against both anaerobic and aerobic Gram-positive bacteria that are resistant to various chemotherapeutic drugs (beta-lactam and macrolide antibiotics, tetracyclines, co-trimoxazole). Then the aim of this work was to verify experimentally the possible pharmacological interactions between teicoplanin and oral hypoglycemic (phenformin and glibenclamide), or oral anticoagulant (warfarin) or bronchodilator (theophylline) drugs. Teicoplanin (3 15 mg/kg/die i.p. for 4 days) administration to the rat did not significantly (p > 0.05) modify the glycemia, prothrombin and partial thromboplastin times, the hypoglycemic effect of phenformin (2.5 mg/kg/die os for 4 days) and glibenclamide (0.5 mg/kg/die os for 4 days) or the anticoagulant effect of warfarin (0.5 mg/kg/die os for 4 days); moreover it did not significantly (p > 0.05) modify the pharmacokinetics of aminophylline (5 mg/kg i.v.) on the rabbit. In conclusion our results documented that teicoplanin does not interfere with phenformin, glibenclamide, or sodium warfarin activities nor with aminophylline pharmacokinetics. PMID- 8459262 TI - Possible influence of assay methods in studies of the pharmacokinetics of antibiotics. AB - In the present research, levels of gentamicin (GM) in serum and carrageenan pleural exudate from the rat have been compared, using three evaluation methods: microbiological assay (MA), enzyme-immunoassay (EMIT) and fluorescence immunoassay (TDX). In a first study, the evaluations carried out by MA and EMIT have furnished comparable data in serum, while statistically significant differences were verified at all times in pleural exudate. On the contrary, in a second study, while the evaluations carried out by MA and EMIT, at all times and in both biological fluids, have produced similar data, the evaluation carried out by TDX consistently supplied higher results, with statistically significant differences at some times (5 min and 60 min for serum, 30 min and 60 min for exudate). Some possible interpretations of these results are discussed. PMID- 8459263 TI - Antimicrobial chemoimmunoprophylaxis in colorectal surgery with cefotetan and thymostimulin: prospective, controlled multicenter study. Italian Study Group on Antimicrobial Prophylaxis in Abdominal Surgery. AB - Surgical antimicrobial prophylaxis was performed with a controlled study on 859 evaluable patients randomized into two groups treated with chemoprophylaxis only or chemo- and immunoprophylaxis in colorectal surgery. Immuno and chemoprophylactic treatment (425 patients) consisted of 70 mg i.m. thymostimulin per day for 7 days beginning 48 h before surgery plus 2 g cefotetan at the moment of induction of anesthesia; the other group (434 patients) received only the single dose of antibiotic. Results in the two different groups were significantly different regarding abdominal abscess and the total infectious episodes in the surgical site with lower frequency in patients receiving both thymostimulin and the antibiotic (cefotetan). Moreover the respiratory tract infections were more than double in those patients not treated with perioperative immunotherapy. Stratifying patients on the basis of grade of skin test reaction, we observed a significantly lower percentage of surgical site infection in hypoergic patients receiving chemo- and immunoprophylaxis. PMID- 8459264 TI - Second-line chemotherapy with mitoxantrone as a single agent in metastatic breast cancer. AB - Ninety-three evaluable patients with metastatic breast cancer previously treated with chemotherapy, received mitoxantrone as a single agent (14 mg/m2, by rapid intravenous infusion, once every 3 weeks). Patients received a median of 7 courses (range 2 to 18), with a mean cumulative total dose of 133 mg (range 36 to 342). A complete response (CR) was achieved in 2 patients (2%). Partial response (PR) was observed in 23 patients (25%). The overall response rate (CR+PR) was thus 27%, with a median duration of 9 months (range 3 to 18). Responses were observed in all metastatic sites, except for brain and peritoneum. Stabilization (S) occurred in 26 patients (28%). The remaining 42 patients (45%) showed clear progression of their metastatic disease while on therapy. The actuarial 24-month survival for the whole group was 13%, increasing to 29% in responders (CR+PR), as compared with only 10% for non-responders (S+P; P < 0.0001). Mitoxantrone was generally well tolerated; nausea, vomiting and hair loss were mild. Nine out of 625 treatment cycles resulted in leukopenic fever with uneventful recovery. All patients had serial MUGA scans; 3 patients (cumulative total doses of 200, 250 and 342 mg, respectively) developed a significant drop in the left ventricular ejection fraction. Clinical evidence of congestive heart failure was observed in one patient who had received prior doxorubicin-based adjuvant chemotherapy. Mitoxantrone seems to be as effective as other drugs given singly or in combination as second-line chemotherapy in patients with metastatic breast cancer. Its low morbidity makes its use attractive in this setting. PMID- 8459265 TI - A phase II study of carboplatin and cyclophosphamide in advanced ovarian carcinoma. AB - Forty-two patients affected by either stage III and IV ovarian cancer with residual tumor after surgery or recurrent ovarian cancer entered a phase II study of the combination carboplatin 300 mg/m2 and cyclophosphamide 600 mg/m2 every 28 days. Thirty-eight patients were evaluable for response and of these 27 obtained complete or partial remission with a 71% overall remission (clinical complete remission 45%; partial remission 26%). Treatment tolerability was on the whole good. The most frequent side effects were leukopenia (76%), anemia (67%) and nausea/vomiting (60%). Thrombocytopenia was present in 31% of the patients, but nearly always to a mild degree except for one grade 4 case. No other grade 4 side effect was observed. We did not observe any cases of nephrotoxicity and only two patients complained of paresthesia. This carboplatin-cyclophosphamide combination in advanced ovarian carcinoma produces comparable results, in terms of objective responses, to those obtained with standard cisplatin-based regimens, with suggestion of a better toxicological profile. PMID- 8459266 TI - Folinic acid does improve 5-fluorouracil activity in vivo. Results of a phase III study comparing 5-fluorouracil to 5-fluorouracil and folinic acid in advanced colon cancer patients. AB - We report the results of a phase III trial in which we compared 5-fluorouracil (5 FU) to 5-FU and folinic acid (FA) in 150 previously untreated metastatic colon cancer patients. Patients were randomized in the ratio of 1:2 to receive 5-FU (370 mg/m2, i.v., for 5 days) in arm A or equidose 5-FU plus FA (200 mg/m2, i.v., for 5 days) for arm B, each cycle being repeated every 4 weeks. Five of 49 evaluable arm A patients (10.2%) and 31 of 97 arm B (31.9%) achieved a complete or partial response (p < or = 0.01). Median survival time of arm A patients was 6 months (mean: 6.18), while it was 8 months (mean: 9.01) for arm B cases (p < or = 0.05). In conclusion, our data indicate that FA can enhance 5-FU activity and that this combination is an effective palliative treatment for metastatic colon cancer patients. PMID- 8459267 TI - Ondansetron plus dexamethasone in the control of high dose cisplatin-induced emesis. AB - Twenty-two patients who underwent chemotherapy with cisplatin (CDDP) at doses > 100 mg/m2 also received antiemetic treatment comprised of the combination of ondansetron plus dexamethasone. The results obtained have shown a good activity from this combination with these high doses of CDDP, with a response of 81.8% (complete+major protection). There were also three therapeutic failures in patients with a few negative prognostic characteristics. It is our intention to use a benzodiazepine and adequate psychological support in an attempt to increase the response percentages in these kinds of patients. PMID- 8459268 TI - Three-dimensional organization of optokinetic responses in the rabbit. AB - 1. Three-dimensional rotations of both eyes were measured in alert rabbits during optokinetic stimulation about axes lying in the horizontal plane or about an earth-vertical axis, with either one or both eyes viewing the stimulus. Optokinetic stimulus speed was 2 degrees /s, either continuous or alternating in polarity (triangular stimulus). In addition to the gains of the responses, the orientations of the response axes relative to the stimulus axes were determined. 2. In comparison to the response to constant-speed optokinetic stimulation about the vertical axis, the response to constant-speed optokinetic stimulation about horizontal axes was characterized by the lack of a speed buildup. In many cases, slow phase tracking was good as long as the eye was within the central oculomotor range but deteriorated when eye deviation became more eccentric and fast phases failed to be generated. These features suggest that the optokinetic reflex about horizontal axes functions as a position-control system, rather than as a velocity control system. 3. Binocular optokinetic stimulation at constant speed (2 degrees/s) about the roll axis (0 degrees azimuth horizontal axis) elicited disconjugate responses. Although the gain of the response was not significantly different in the two eyes (0.38 for downward and 0.44 for upward stimulation), the response axes of the two eyes differed by as much as 51 degrees. 4. Monocular, horizontal axis optokinetic stimulation at constant speed elicited responses that were grossly dissociated between the two eyes. The magnitude of the responses was anisotropic in that it varied with the azimuthal orientation of the stimulus axis; the maximum gain for each eye (0.41 for the seeing and 0.33 for the covered eye) was at 135 degrees azimuth for each eye. The axis orientation and direction (sense of rotation) of the optokinetic stimulus eliciting the maximal response for each eye coincided with the optic flow normally associated with the maximal excitation of the corresponding ipsilateral anterior canal. 5. Binocular, triangular optokinetic stimulation with small excursions (+/- 10 degrees), which avoided the saturation problems of constant speed stimulation, elicited adequate responses without systematic directional asymmetries. Gain was approximately 0.9 for all stimulus axis orientations in the horizontal plane. 6. During monocular stimulation with triangular stimuli, the response of the seeing eye showed a gain of approximately 0.5 for all orientations of the stimulus axis. In contrast, the covered eye showed anisotropic responses, with a maximum gain of approximately 0.5 during stimulation of the seeing eye about its 45 degree axis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8459269 TI - Nociceptive neurons of the raccoon lateral thalamus. AB - 1. Responses to noxious mechanical and thermal stimuli were examined in 48 thalamic neurons in barbiturate or chloralose-anesthetized raccoons, with special attention to neurons whose peripheral receptive fields (RFs) included glabrous skin of the forepaw. Recording loci were in the core of the ventrobasal complex (VB; n = 32), its ventral or dorsal border (n = 5), or the medial division of the posterior nuclear group (POm; n = 11). 2. Twenty-one VB neurons and 7 POm neurons were classed as wide dynamic range (WDR), whereas 2 VB neurons and 4 POm neurons were classed as nociceptive specific (NS). Response properties of 14 light touch (LT) neurons located in VB were also examined. 3. WDR and NS neurons were not segregated, but rather were intermixed along the ventral and dorsal borders of VB, as well as in POm, and WDR and LT neurons were intermixed in the core of VB. Within the VB core, both LT and WDR neurons were somatotopically organized. 4. All WDR neurons had larger high-threshold than low-threshold RFs, and this difference was greater for POm neurons than for VB neurons. RF areas of LT neurons and low-threshold RF areas of WDR neurons were comparable to those previously reported for raccoon VB units. 5. Out of 25 WDR cells tested, 20 had heat thresholds > 53 degrees C; the range of thresholds in the remaining 5 was 49 53 degrees C. Four out of five NS neurons tested had heat thresholds > 53 degrees C; the threshold of the fifth was 51 degrees C. Of the six neurons with heat thresholds < or = 53 degrees C, two each were in the core of VB, along the border of VB, and in POm. 6. Sensitization to heat after a mild heat injury to the glabrous RF (53 degrees C for 90 s, or 55 degrees C for 30 s) occurred in 8 out of 16 neurons tested, and persisted for up to 2 h. Median thresholds decreased from > 53 degrees C before injury to 47 degrees C after injury, and responses to suprathreshold stimuli were enhanced. There was a significantly greater likelihood (P = 0.02) for sensitization to occur in POm neurons (6/7) than in VB neurons (2/9). 7. It is suggested that a small proportion of neurons located in VB and POm contribute to the sensation of heat pain. Furthermore, sensitization of these neurons may contribute to heat hyperalgesia after an injury to glabrous skin. PMID- 8459270 TI - Neural circuit tuning fly visual interneurons to motion of small objects. I. Dissection of the circuit by pharmacological and photoinactivation techniques. AB - 1. Visual interneurons tuned to the motion of small objects are found in many animal species and are assumed to be the neuronal basis of figure-ground discrimination by relative motion. A well-examined example is the FD1-cell in the third visual neuropil of blowflies. This cell type responds best to motion of small objects. Motion of extended patterns elicits only small responses. As a neuronal mechanism that leads to such a response characteristic, it was proposed that the FD1-cell is inhibited by the two presumably GABAergic and, thus, inhibitory CH-cells, the VCH- and the DCH-cell. The CH-cells respond best to exactly that type of motion by which the activity of the FD1-cell is reduced. The hypothesis that the CH-cells inhibit the FD1-cell and, thus, mediate its selectivity to small moving objects was tested by ablating the CH-cells either pharmacologically or by photoinactivation. 2. After application of the gamma aminobutyric acid (GABA) antagonist picrotoxinin, the FD1-cell responds more strongly to large-field than to small-field motion, i.e., it has lost its small field selectivity. This suggests that the tuning of the FD1-cell to small moving objects relies on a GABAergic mechanism and, thus, most likely on the CH-cells. 3. The role of each CH-cell for small-field tuning was determined by inactivating them individually. They were injected with a fluorescent dye and then ablated by laser illumination. Only photoinactivation of the VCH-cell eliminated the specific selectivity of the FD1-cell for small-field motion. Ablation of the DCH cell did not significantly change the response characteristic of the FD1-cell. This reveals the important role of the VCH-cells in mediating the characteristic sensitivity of the FD1-cell to motion of small objects. 4. The FD1-cell is most sensitive to motion of small objects in the ventral part of the ipsilateral visual field, whereas motion in the dorsal part influences the cell only weakly. This specific feature fits well to the sensitivity of the VCH-cell to ipsilateral motion that is most pronounced in the ventral part of the visual field. The spatial sensitivity distribution of the FD1-cell matches also the characteristics of figure-ground discrimination and fixation behavior. PMID- 8459271 TI - Neural circuit tuning fly visual neurons to motion of small objects. II. Input organization of inhibitory circuit elements revealed by electrophysiological and optical recording techniques. AB - 1. The FD1-cell in the visual system of the fly is an identified visual interneuron that is specifically tuned to motion of small objects. In the companion paper it was shown that this response property is mediated by one of the two CH-cells, the VCH-cell, that inhibits the FD1-cell by GABAergic synapses. Here the input organization of the two CH-cells is analyzed by both electrophysiological and optical recording techniques. 2. Both CH-cells are excited by front-to-back motion in the ipsilateral and by back-to-front motion in the contralateral visual field. They respond maximally to binocular rotatory motion about the vertical axis of the animal. The latter response is only slightly less than the sum of the corresponding monocular response components. The relative contribution of the ipsi-and contralateral eye to the binocular response varies considerably between flies. In extreme cases it is dominated by either the ipsi- or the contralateral eye. The two CH-cells are not equally sensitive along the vertical axis of the eye. The DCH-cell has its sensitivity maximum in the dorsal part, the VCH-cell in the ventral part of the visual field. 3. The CH-cells have two arborizations, a large one in the posterior part of the third visual neuropil, the lobula plate, and a smaller one in the ipsilateral ventrolateral brain. With the calcium-sensitive dye fura-2 as an activity marker, it is analyzed which of these branches of the CH-cells receive the ipsi- and contralateral motion input, respectively. During motion in the preferred direction within the ipsilateral visual field, calcium accumulates only in the CH cells' main arborization in the lobula plate but not in their branches in the ventrolateral brain, indicating that the arborization in the lobula plate is postsynaptic to the ipsilateral input. In contrast, contralateral motion in the preferred direction leads to calcium accumulation in both arborizations, suggesting that both are postsynaptic to contralateral input elements. During preferred direction motion in the upper or lower part of the ipsilateral visual field, calcium accumulates in only dorsal or ventral branches of the CH-cells' arborization in the lobula plate, respectively, revealing that their ipsilateral motion input is organized retinotopically. Because this arborization, most likely, is also the main output terminal of the CH-cells, it is both pre- and postsynaptic. This specific neuronal design is discussed with respect to its consequences for the mechanism of tuning the FD1-cell to motion of small objects. PMID- 8459272 TI - Kinetic properties of a slow apamin-insensitive Ca(2+)-activated K+ current in guinea pig vagal neurons. AB - 1. The calcium-activated outward current (gKCa,2) following an action potential was recorded from neurons in the guinea pig dorsal motor nucleus of the vagus (DMV). gKCa,2 was activated after a delay after the action current and had a distinct rising phase in contrast to the apamin sensitive calcium-activated current in rat DMV neurons (gKCa,1). 2. The time course of gKCa,2 was well described by function of the form A*[exp(t/tau 1)-exp(t/tau 2)], where tau 1 = 1.42 +/- 0.05 (SE) s and tau 2 = 555 +/- 24 ms. 3. Increasing calcium influx by firing multiple action currents lead to an increase in the peak amplitude of gKCa,2 with no change in its kinetics. In cells loaded with low concentrations of ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), gKCa,2 was smaller in amplitude but its time course was similar to that in cells not loaded with EGTA. 4. When preceded by a conditioning influx of calcium, the amplitude and time course of gKCa,2 was identical to one with no conditioning influx. These results show that, after influx of calcium, a potassium current with stereotyped amplitude and kinetics is generated. 5. These data are consistent with the idea that the source of calcium for activation of gKCa,2 is not the extracellular space. PMID- 8459273 TI - Organization of response areas in ferret primary auditory cortex. AB - 1. We studied the topographic organization of the response areas obtained from single- and multiunit recordings along the isofrequency planes of the primary auditory cortex in the barbiturate-anesthetized ferret. 2. Using a two-tone stimulus, we determined the excitatory and inhibitory portions of the response areas and then parameterized them in terms of an asymmetry index. The index measures the balance of excitatory and inhibitory influences around the best frequency (BF). 3. The sensitivity of responses to the direction of a frequency modulated (FM) tone was tested and found to correlate strongly with the asymmetry index of the response areas. Specifically, cells with strong inhibition from frequencies above the BF preferred upward sweeps, and those from frequencies below the BF preferred downward sweeps. 4. Responses to spectrally shaped noise were also consistent with the asymmetry of the response areas. For instance, cells that were strongly inhibited by frequencies higher than the BF responded best to stimuli that contained least spectral energy above the BF, i.e., stimuli with the opposite asymmetry. 5. Columnar organization of the response area types was demonstrated in 66 single units from 16 penetrations. Consistent with this finding, it was also shown that response area asymmetry measured from recordings of a cluster of cells corresponded closely with those measured from its single unit constituents. Thus, in a local region, most cells exhibited similar response area types and other response features, e.g., FM directional sensitivity. 6. The distribution of the asymmetry index values along the isofrequency planes revealed systematic changes in the symmetry of the response areas. At the center, response areas with narrow and symmetric inhibitory sidebands predominated. These gave way to asymmetric inhibition, with high-frequency inhibition (relative to the BF) becoming more effective caudally and low-frequency inhibition more effective rostrally. These response types tended to cluster along repeated bands that paralleled the tonotopic axis. 7. Response features that correlated with the response area types were also mapped along the isofrequency planes. Thus, in four animals, a map of FM directional sensitivity was shown to be superimposed on the response area map. Similarly, it was demonstrated in six animals that the spectral gradient of the most effective noise stimulus varied systematically along the isofrequency planes. 8. One functional implication of the response area organization is that cortical responses encode the locally averaged gradient of the acoustic spectrum by their differential distribution along the isofrequency planes. This enhances the representation of such features as the symmetry of spectral peaks and edges and the spectral envelope.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8459274 TI - Receptive properties of myelinated primary afferents innervating the inflamed urinary bladder of the cat. AB - 1. The present study has investigated the receptive properties of myelinated mechanoreceptive primary afferents innervating the inflamed urinary bladder of the cat. In 15 experiments, 20 units were recorded from the dorsal and 3 from the ventral root S2. Before inflammation the afferents had no resting activity and responded consistently to increases of intravesical pressure evoked by isotonic distension or isovolumetric contractions. All units were studied before and after the onset of an acute inflammation induced by intraluminal injection of mustard (1-2.5%) or turpentine oil (50%), which are known to induce an acute cystitis. 2. Eleven out of 14 units tested with mustard oil and 5/9 units tested with turpentine oil were activated at short latency. The response could not be explained by a concomitant increase of intraluminal pressure resulting from the intravesical injection of the irritant. This suggests that a large proportion of mechanosensitive afferents has an additional chemosensitivity. 3. After removal of the irritants and with empty bladder, all afferent units exhibited irregular ongoing activity with intermittent high-frequency bursts. Such ongoing activity was entirely absent in myelinated afferents supplying the noninflamed bladder. The median rate of ongoing activity was significantly higher after mustard oil (1.65 imp/s) than after turpentine oil treatment (0.05 imp/s) 1 h after chemical stimulation. Post-hoc analysis revealed that afferents that developed high levels of ongoing activity had steeper stimulus response functions to changes of intravesical pressure before inflammation. 4. The stimulus-response function of vesical afferents changed characteristically in the inflamed bladder. Within 30 min of mustard oil treatment, the responses of some units to bladder filling was transiently enhanced, but later the units desensitized to this stimulus. However, there was no significant change of the stimulus-response function of six afferents studied before and for 2 h after induction of the inflammation. By contrast, the afferents exhibited significant increases of their mechanosensitivity after turpentine treatment. 5. In conclusion, sacral myelinated mechanoreceptive afferents supplying the urinary bladder are chemosensitive. Their receptive properties change rather uniformly when the tissue becomes inflamed, and, on the basis of these changes, it is not possible to differentiate subpopulations of primary afferents. The induction of ongoing activity and the increased responses to intravesical pressure stimuli in the inflamed organ, together with central changes that may occur under these conditions, are probably responsible for changes of bladder motility and sensations that arise during cystitis. PMID- 8459275 TI - Groupings of nonpyramidal and pyramidal cells with specific physiological and morphological characteristics in rat frontal cortex. AB - 1. Physiological and morphological properties of layer V non-pyramidal and pyramidal cells in isolated slices of frontal cortex from young rats (16-22 days postnatal) were studied by whole-cell, current-clamp recording of visualized cell bodies coupled with intracellular staining by biocytin at 26-27 degrees C. 2. Plotting of spike width at half amplitude against input resistance revealed two physiological categories of nonpyramidal cells. One class (n = 29) had input resistances lower than 400 M omega and spike widths at half amplitude shorter than 0.8 ms; the other (n = 22) had input resistances higher than 400 M omega and spike widths longer than 0.8 ms. According to their spike firing characteristics, the former are called fast-spiking (FS) cells, and the latter low-threshold spike (LTS) cells. 3. Resting potentials were more negative in FS cells than in LTS cells. Membrane time constants in LTS cells were four times larger than those of FS cells. Afterhyperpolarizations (AHPs) following action potentials consisted of a single component in FS cells, but two components with early and late peaks were observed in LTS cells. AHPs of FS cells had faster time-to-peak and larger amplitude than the early component of the AHPs of LTS cells. 4. Low-threshold spikes induced by depolarizing current pulses were observed at hyperpolarized potentials in LTS cells, but not in FS cells. The low-threshold spikes in LTS cells could be activated at hyperpolarized potentials by synaptic potentials. 5. Spike trains elicited by depolarizing current pulses in FS cells showed almost no spike-frequency adaptation, whereas those in LTS cells showed adaptation. 6. Excitatory postsynaptic potentials (EPSPs) of both groups of nonpyramidal cells contained N-methyl-D-aspartate (NMDA) receptor-mediated components. A combination of stimulation-induced EPSPs with depolarization caused repetitive firing in FS cells that was abolished by NMDA receptor blockers. Repetitive firing was not observed in LTS cells under these conditions. 7. The somal size of the two classes of nonpyramidal cells was similar. FS cells were all multipolar in shape, whereas LTS cells included both multipolar and bitufted types. The dendrites of some FS cells extended up into layers II/III, but there were also other FS cells with their dendrites restricted in layer V. Dendrites of LTS cells were mostly restricted to layer V. Dendrites of FS cells were mostly smooth, but those of LTS cells possessed a modest but consistent population of spines.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8459276 TI - Maximum shortening speed of motor units of various types in cat lumbrical muscles. AB - 1. Isotonic shortening of cat superficial lumbrical muscles was studied during maximal tetanic contractions of single motor units of identified types. For each motor unit, the maximal speed of contraction, Vmax, was determined by extrapolating to zero the hyperbolic relation between applied tension and speed of shortening. 2. The maximal speeds of shortening of motor units formed a continuum with the highest velocities observed for the fast fatigable motor units and the lowest for the slow motor units. 3. On average, the maximum speed of shortening increased with the tetanic tension developed by the motor units. 4. In motor units with isometric twitch contraction times less than 35 ms, these times showed a significant inverse correlation with Vmax. Progressively longer contraction times were associated with rather small changes in Vmax. 5. The implications of these findings on the speed of muscle shortening during motor unit recruitment are discussed. PMID- 8459277 TI - Binaural processing of sound pressure level in cat primary auditory cortex: evidence for a representation based on absolute levels rather than interaural level differences. AB - 1. Single-neuron responses were recorded in high-frequency regions of primary auditory cortex (AI) of anesthetized cats. Best-frequency tone pips were presented to each ear independently via sealed stimulus delivery systems, and the sound pressure level (SPL) at each ear was independently manipulated. Each neuron was studied with many dichotic combinations of SPL, chosen to incorporate a broad range of the two synthetic interaural level variables, interaural level difference (ILD) and average binaural level (ABL). This paper illustrates the common forms of binaural SPL selectivity observed in a sample of 204 single neurons located in AI. 2. Most neurons (> 90%) were jointly influenced by ILD and ABL. A small proportion of bilaterally excitable (EE) neurons responded to ABL rather independently of ILD. Only one neuron was determined to respond to ILD independently of ABL. 3. Nonmonotonic selectivity for one or both of the binaural level cues was evident in > 60% of our sample. Within the most effective range of ILD values, response strength was usually related nonmonotonically to related both to ILD and ABL. We have described units exhibiting this kind of dual nonmonotonic selectivity for the two binaural variables as being influenced by a Two-Way Intensity Network (TWIN). 4. Each of the response forms identified in an earlier study of the gerbil inferior colliculus were found in this study of cat auditory cortex. However the classes were evident in markedly different proportions. In particular, TWIN responses alone accounted for 36.2% of the sample, nearly four times the proportion found in the inferior colliculus in a previous study. 5. Units with similar binaural responses do not necessarily have similar monaural properties. For example, the typically nonmonotonic relation between response strength and ABL was often observed in the absence of a monaurally demonstrable nonmonotonicity. There is no simple relation between a neuron's classification according to the sign of monaural influence and its response to ILD and ABL. In particular, EE neurons exhibited remarkably diverse binaural properties. 6. Since responses of nearly all AI neurons are influenced jointly by ABL and ILD, we contend that single neurons in primary auditory cortex are not specifically tuned to either cue. ILD and ABL are mathematical expressions relating the SPLs at the two ears to each other (as the difference and average, respectively) and any such combination is expressed most simply as a particular combination of SPL at each ear.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8459278 TI - Focal selectivity for binaural sound pressure level in cat primary auditory cortex: two-way intensity network tuning. AB - 1. The influence of sound pressure level (SPL) at the two ears was studied in single-neuron responses recorded in high-frequency regions of primary auditory cortex (AI) of anesthetized cats. For each unit, many binaural combinations of SPL were tested by using best-frequency tone pips presented to each ear independently via sealed stimulus delivery systems. In the preceding paper, we illustrated the different forms of response observed in our sample of units. Here we explore in more detail the mechanisms underlying the properties of the largest single class of binaural response, characterized by joint nonmonotonic tuning to the SPLs at the two ears. We have described such units as being influenced by a Two-Way Intensity Network (TWIN). 2. Under binaural conditions, 62% of our sample of well documented neurons (81/130) exhibited a nonmonotonic relation between response magnitude and the SPL at one or the other ear. Of these units, 47 displayed clear bilateral nonmonotonicity (TWIN tuning), 17 units displayed only unilateral nonmonotonicity, and an additional 17 units showed intermediate (or transitional) characteristics between unilateral and bilateral nonmonotonicity. These characteristics can also be described in terms of average binaural level (ABL) and interaural level difference (ILD). Thus there is commonly a nonmonotonic relation between response magnitude and ABL and sometimes a TWIN tuning to ABL and ILD. The distribution of best frequencies for TWIN neurons is broad. 3. Under monaural conditions, TWIN neurons exhibit diverse properties. Some are responsive only under binaural conditions [i.e., predominantly binaural (PB)]. Some monaurally responsive TWINs are contralaterally excitable and ipsilaterally unresponsive (EO), some are ipsilaterally excitable and contralaterally unresponsive (OE), and a few are bilaterally excitable (EE). Monaural rate/level functions are monotonic for some of these neurons and nonmonotonic for others. Neurons of the PB class have previously been found to have nonmonotonic selectivity for ILDs near zero. In this study we have found that virtually all PB neurons are also nonmonotonically selective for ABL with different PB neurons having different best ABLs. 4. For TWIN neurons that respond monaurally, it is possible to demonstrate a mixed binaural influence. The optimal stimulus (or best binaural combination) for a TWIN neuron is associated with binaural facilitation. Flanking the most effective combination of ABL and ILD are less effective combinations that generate lower response magnitudes, either through threshold effects (at low SPLs) or through binaural suppression (at higher SPLs).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8459279 TI - Multiple-tooth receptive fields of single human periodontal mechanoreceptive afferents. AB - 1. Single-unit impulse activity from 25 mechanoreceptive afferents was recorded in the human inferior alveolar nerve using tungsten microelectrodes. All of these afferents were considered to originate in periodontal receptors because they showed responses to mechanical stimulation of one or more teeth but not to stimulation of the gingiva. 2. For each afferent isolated, forces with "ramp-and hold"-shaped profiles of similar magnitudes (261 +/- 21 mN, mean +/- SD) were applied to the incisors, the canine, and the first premolar on the recording side, and the contralateral central incisor in four horizontal directions: lingual, labial, mesial, and distal. For a few of the afferents, forces were also applied in the axial directions (up and down). Both static and dynamic response components were analyzed. 3. For about one half of the tested afferents, the receptive fields were restricted to a single tooth. The remainder (52%) responded to stimulation of a group of teeth (on average 3.1 teeth), which typically showed contact between their crowns. 4. Afferents responding to loading of multiple teeth showed their strongest responses to forces applied to a particular tooth, with a gradual decline in the responsiveness to the adjacent teeth. 5. The stimulation directions eliciting the strongest afferent responses for the most sensitive tooth were approximately evenly distributed over the four stimulation directions, except for some bias toward the lingual direction. In contrast, loading of the adjacent teeth most often showed the strongest responses in the mesial or distal directions, in most cases toward the most sensitive tooth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8459280 TI - Gustatory neural coding in the monkey cortex: the quality of sweetness. AB - 1. We analyzed the activity of single neurons in gustatory cortex of alert cynomolgus monkeys in response to the four basic taste stimuli and to a range of chemicals, all of which are predominantly sweet to humans. 2. We recorded taste evoked responses from a cortical area that measured 4.0 mm in its anteroposterior extent, 5.6 mm dorsoventrally and 2.2 mm mediolaterally. Taste-responsive neurons constituted 4.7% of the 3,066 neurons tested in the course of 66 recording tracks. Nongustatory cells included those responsive to mouth movement (34.1%), tongue touch (1.9%), stimulus approach (0.7%), and tongue extension (0.5%). The functions of 58.2% of the cells we isolated could not be determined. 3. The mean breadth of tuning of these cortical taste neurons was a moderate 0.59 (range 0.00 0.93). 4. There was no evidence that taste cells with similar functional attributes were clustered in the cortex, i.e., there was no apparent topographic organization of taste qualities. 5. A taste space was generated from the correlations among patterns of neural activity evoked by the stimulus array. Within the space, NaCl was most isolated from other stimuli; the profiles elicited by HCl, quinine HCl, and water were all moderately intercorrelated and were clearly distinct from the cluster of sweet stimuli. 6. The 19 sweet chemicals formed a coherent cluster centered on the simple carbohydrates (glucose, fructose, sucrose, maltose) and sorbitol. Nearest this core were calcium cyclamate, aspartame, and cran-raspberry juice. In the next concentric ring were acesulfame potassium, xylose, xylitol, sorbose, polycose, and myoinositol. Increasingly distant from the sugars were sodium saccharin, stevioside, neohesperidin DHC, L-tryptophan and monellin. 7. We compared these results with those of a human psychophysical study of sweet stimuli. Using the position of glucose as a reference, we measured the distances to all other stimuli that were common to the two studies (n = 15). The correlation between the human psychophysical data and those derived from evoked activity in the macaque cortex was +0.82. 8. The high correlation between human psychophysical and macaque electrophysiological data implies that the subtle distinctions among stimuli that are predominantly sweet are quite similar for these two species and reinforces the value of this neural model for human taste perception. PMID- 8459281 TI - Gravitoinertial force level influences arm movement control. AB - 1. The ability to move the forearm between remembered elbow joint angles immediately after rapid increases or decreases of the background gravitoinertial force (G) level was measured. The movements had been well-practiced in a normal 1G environment before the measurements in high-(1.8G) and low-force (0G) environments. The forearm and upper arm were always unsupported to maximize the influence of altered G-loading and to minimize extraneous cues about arm position. 2. Horizontal and vertical movement planes were studied to measure the effects of varying the G load in the movement plane within a given G background. Rapid and slow movements were studied to assess the role of proprioceptive feedback. 3. G level did not affect the amplitude of rapid movements, indicating that subjects were able to plan and to generate appropriate motor commands for the new G loading of the arm. The amplitude of slow movements was affected by G level, indicating that proprioceptive feedback is influenced by G level. 4. The effects of G level were similar for horizontal and vertical movements, indicating that proprioceptive information from supporting structures, such as the shoulder joint and muscles, had a role in allowing generation of the appropriate motor commands. 5. The incidence and size of dynamic overshoots were greater in 0G and for rapid movements. This G-related change in damping suggests a decrease in muscle spindle activity in 0G. A decrease in muscle spindle activity in 0G and an increase in 1.8G are consistent with the results of our prior studies on the tonic vibration reflex, locomotion, and perception of head movement trajectory in varying force backgrounds. PMID- 8459282 TI - Pharmacologically induced elements of the hunting and feeding behavior in the pteropod mollusk Clione limacina. I. Effects of GABA. AB - 1. The pteropod mollusk Clione limacina is a predator, feeding on the small pteropod mollusk Limacina helicina. Injection of gamma-aminobutyric acid (GABA) into the hemocoel of the intact Clione evoked some essential elements of the hunting and feeding behavior, i.e., protracting the tentacles, opening the mouth, and triggering the rhythmic movements of the buccal mass. This pattern resembled that evoked by presentation of the prey: Clione grasped the Limacina by its tentacles, extracted the prey's body from the shell and then swallowed it. 2. In electrophysiological experiments, several targets of GABA action have been found: 1) direct application of GABA to isolated cerebral motor neurons projecting to the protractor muscles of tentacles resulted in their excitation; 2) GABA activated the feeding rhythm generator located in the buccal ganglia; 3) GABA exerted excitatory or inhibitory effects on the receptor cells of statocysts, the effects being mediated by the efferent input to these cells; 4) GABA suppressed the defense reaction, which is an inhibition of the locomotor activity and of tentacle motor neurons, arising in response to stimulation of the head afferents; and 5) GABA potentiated an excitatory action of the serotoninergic metacerebral cells on the feeding rhythm generator. 3. Effects of GABA on the tentacle motor neurons and the feeding rhythm generator are pharmacologically distinguishable. The action of GABA on the feeding rhythm generator was mimicked by baclofen (which activates the GABAB receptors in mammalian neurons) and was not sensitive to bicuculline (the GABAA receptor antagonist in mammals). On the other hand, bicuculline competitively inhibited the GABA-induced excitation of the tentacle motor neurons. 4. GABAergic neurons have been located in the cerebral, pedal, and buccal ganglia by means of immunohistochemical methods. PMID- 8459284 TI - Functional differences between afferent fibers in the hypogastric and pelvic nerves innervating female reproductive organs in the rat. AB - 1. The uterus, cervix, and vaginal canal are innervated by afferent fibers in the hypogastric and pelvic nerves. Four studies compared the innervation territory and sensitivity to peripheral stimuli of the two sets of fibers in adult virgin rats. 2. Innervation territory was studied anatomically by injecting different fluorescent dyes into different parts of the reproductive, lower urinary, and lower digestive tracts and examining retrogradely labeled neurons in dorsal root ganglia. It was also studied electrophysiologically in anesthetized rats by summing potentials evoked in branches of the two nerves by electrical stimulation of different parts of the reproductive tract. 3. In both studies sensory innervation of the reproductive tract shifted from the pelvic to the hypogastric nerve (i.e., shifted entry into the spinal cord from the L6-S1 to the T13-L3 dorsal root ganglia, respectively) as the dye or stimulating electrode shifted from the vaginal entrance to the uterine horns, with fibers from both nerves densely innervating the cervix region (i.e., entering the spinal cord through both sets of ganglia). The anatomic results suggested that the regions innervated by fibers in one nerve might also be innervated by a small component of normally quiescent fibers in the other nerve. 4. Response sensitivity was studied electrophysiologically by simultaneously recording multiunit activity in branches of the hypogastric and pelvic nerves in two ways. First, in intact, anesthetized rats, activity was recorded during mechanical stimulation of the reproductive tract (distension of the vagina and uterus, probing the cervix). Second, in an in vitro organ preparation of the uterus and vagina, activity was recorded during chemical stimulation through the uterine artery with bradykinin, serotonin, NaCN, CO2, and KCl. 5. Pelvic nerve fibers were markedly more sensitive than hypogastric nerve fibers to uterine and cervical mechanostimulation. Similarly, pelvic nerve fibers were more likely to respond or responded more vigorously than hypogastric nerve fibers to all chemical stimuli (except KCl). 6. These results provide strong evidence that afferent fibers in the pelvic and hypogastric nerves of nulliparous adult rats subserve different functions in reproduction and sensation. Pelvic nerve fibers seem closely tied to sensory and behavioral processes associated with mating and conception, whereas hypogastric fibers seem closely tied to pregnancy and nociception, with fibers in both nerves serving functions during parturition. PMID- 8459283 TI - Pharmacologically induced elements of the hunting and feeding behavior in the pteropod mollusk Clione limacina. II. Effects of physostigmine. AB - 1. A contact of the pteropod mollusk Clione limacina with its prey (small pteropod mollusk Limacina helicina) evokes a complex pattern of hunting and feeding behavior: protraction of tentacles to seize the prey, activation of buccal apparatus to swallow the prey, activation of locomotor system (speeding up of wing beating), reversal of reaction to tactile stimulation of the head, loss of normal (vertical) orientation in space, and swimming in circles. After injection of physostigmine (PhS), the acetylcholinesterase inhibitor, into the hemocoel of intact Clione, all these manifestations of the hunting and feeding behavior could be evoked by tactile stimulation of the head, or they arose spontaneously. 2. In the preparation of the isolated CNS, the effect of PhS on the neural networks controlling different aspects of the hunting and feeding behavior was studied by recording from neurons monitoring activity of different networks (< or = 4 neurons simultaneously). Tactile stimulation of the head was mimicked by a short-term electrical stimulation of the corresponding nerve. Before PhS application, the nerve stimulation evoked elements of the defense reaction, i.e., long-lasting inhibition of all main motor control systems: the locomotor network in the pedal ganglia, the tentacle control network in the cerebral ganglia, and the network controlling radula and hook movements in the buccal ganglia. However, after PhS application, the same stimulus evoked a long lasting bout of excitation in all the three networks accompanied by activation of the heart-exciting neuron as well as by a modification of the activity of statocyst receptor cells controlling Clione's spatial orientation (the "fictive hunting bout"). Similar hunting bouts could arise spontaneously. 3. Injection of acetylcholine (ACh) into the hemocoel of intact Clione was less effective than injection of PhS. After ACh injection, reversal of reaction to head stimulation was observed in < or = 20% of the experiments (the percentage of positive results was higher if ACh was injected into the head just over the CNS). Bath application of ACh to the isolated CNS did not produce the hunting bouts. However, a short term local application of ACh to the cerebral ganglia in the isolated CNS resulted in activation of the main motor systems controlling locomotion, protraction of tentacles, and movements of buccal mass. 4. During spontaneous PhS induced bouts, excitation of different networks involved in hunting behavior was sometimes not quite synchronous. Different networks could be excited in variable order over a period of up to several seconds.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8459285 TI - Neuronal responses to stimulation of the cervix, uterus, colon, and skin in the rat spinal cord. AB - 1. Previous studies in the rat have shown that the hypogastric nerve conveys input from the cervix and uterus mainly to the T13-L3 segments of the spinal cord, whereas the pelvic nerve conveys input from the cervix and vaginal canal mainly to the L6-S2 segments. 2. To study the effects of this input, the dorsal horns of the T13-L1, L6-S2, and L4-L5 segments in 13 decerebrate, T10-spinalized, unanesthetized, and paralyzed adult female rats in estrus were searched for neurons responsive to gentle mechanical stimulation of the cervix. The 87 neurons found were then further tested for their responses to gentle mechanical stimulation of the skin and to distension of both uterine horns, distension of the colon, and shearing stimulation of the colon and vaginal canal. 3. Neurons responsive to cervix stimulation, primarily by excitation, were readily found in the ventral part of the dorsal horn in T13-L1 and throughout the dorsal horn in L6-S2. Cervix-responsive neurons were less readily found throughout the dorsal horn in L4-L5, where 25% were inhibited by the stimulation. All but one neuron had cutaneous receptive fields. 4. The 30 cervix-responsive neurons in T13-L1 had large bilateral cutaneous receptive fields covering the perineum and hind-limbs. Most (76%) also responded, primarily by excitation, to uterine distension, as well as to colonic stimulation (59%). More than half were activated by both types of stimulation. 5. The 33 cervix-responsive neurons in L6-S2 had cutaneous receptive fields in the same regions as those in T13-L1, but generally smaller, particularly for neurons in the dorsal part of the dorsal horn, many of whose receptive fields were confined to the perineum. The L6-S2 neurons also exhibited less convergent input from other visceral structures, particularly the uterus. Fewer neurons (42%) responded to uterine distension, mostly by being inhibited, whereas about the same proportion (51%) responded with excitation to colonic stimulation. Only 24% responded to both uterus and colon. 6. All 24 cervix responsive neurons in medial L4-L5 had small cutaneous receptive fields on the toes, and the neurons received less convergent input from other visceral structures (25% from the uterus, 33% from the colon, 13% from both). 7. These results indicate the presence of an extensive system of neurons throughout the caudal spinal cord of the rat, concentrated in separated thoracolumbar and lumbosacral segments, that is concerned with input from the reproductive tract.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8459286 TI - Responses of neurons in and near the thalamic ventrobasal complex of the rat to stimulation of uterus, cervix, vagina, colon, and skin. AB - 1. Previous studies in the rat and other species have shown that neurons in and near the ventrobasal complex (VB) can be activated by various visceral as well as somatic stimuli. 2. This study examined the responses of 84 single neurons in and near the rostral 2/3 of VB in 19 adult female rats in estrus to mechanical stimulation of the skin (brush, pressure, noxious pinch) and 4 different visceral stimuli, as follows: distension of both uterine horns, mechanical probing of the vagina, gentle pressure against the cervix, and distension of the colon. The rats were studied while under moderate gaseous anesthesia (33% O2-67% N2O + 0.5% halothane) and paralyzed (pancuronium bromide). 3. Of 77 neurons tested with both somatic and visceral stimuli, 70 were responsive to one type and/or the other. Responses to somatic stimuli were immediate with brief afterdischarges to the pinch stimuli. In contrast, responses to visceral stimuli were delayed an average of 9 s with long afterdischarges averaging 2 min. Most viscerally responsive neurons (74%) had somatic receptive fields, often (44%) to noxious pinch. 4. Of the 70 responsive neurons, 43 (61%) responded to 1 or more of the 4 visceral stimuli, primarily with excitation. Most of these 43 neurons (71%) were responsive to uterine distension, whereas fewer responded to stimulation of the cervix (45%), vagina (29%), or colon (34%). 5. Viscerally responsive neurons were preferentially located in regions bordering or near VB. Only 6 of 22 neurons within the core of VB (27%) responded to visceral stimuli, in contrast with 37 of 48 neurons bordering or near VB (77%). 6. The six viscerally responsive neurons within VB all had somatic receptive fields located primarily on the caudal part of the body and were responsive to only one or two of the four visceral stimuli, usually the uterus. The 37 viscerally responsive neurons bordering or near VB were of 3 types. Neurons of the first type (n = 15) were scattered throughout the areas bordering VB and responded to both somatic and visceral stimuli much like VB neurons, except that they showed more visceral convergence. Neurons of the second type (n = 11) were concentrated at the rostral and dorsal borders of VB and responded only to visceral stimuli, mainly the uterus. Neurons of the third type (n = 11) were concentrated ventrally and had very complex, long-lasting and history-dependent response characteristics to both visceral and somatic stimuli.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8459287 TI - Coordination of cortically induced rhythmic jaw and tongue movements in the rabbit. AB - 1. Rhythmic movements of the jaw, tongue, and hyoid that were induced by stimulation of the cortical masticatory area (CMA) were recorded cineradiographically in the anesthetized rabbit. Jaw movements were also recorded by a laser position detector. 2. The evoked jaw movements were classified into four types: small circular (type A), large circular (type B), large vertical (type C), and crescent-shaped (type D). Among these, types B and D resembled the jaw movements of the food transport cycle and those of the chewing cycle in a masticatory sequence. 3. Each type of jaw movement was associated with a particular pattern of tongue and hyoid movements. In general, the tongue protruded during jaw opening and retracted during jaw closure. The hyoid generally moved upward and forward during jaw opening but downward and backward during jaw closure. 4. Electromyograms (EMGs) were recorded from jaw muscles [masseter (Ma) and digastric (Di) muscles], extrinsic tongue muscles [styloglossus (Sg) and genioglossus (Gg) muscles], and hyoid muscles [sternohyoid (Sh) and geniohyoid (Gh) muscles] during cortically induced rhythmic jaw and tongue movements (CRJTMs). These muscles were classified into two groups: group 1 was activated mainly in the jaw opening phase, and group 2 was activated mainly in the jaw closing and power phases. The Di, Gg, and Gh were included in the former, and the Ma, Sg, and Sh were included in the latter. 5. The timings of EMG activation to a jaw movement cycle were relatively constant for the muscles of group 1, irrespective of the types of CRJTMs, whereas those for the muscles of group 2 altered considerably with the different types of CRJTMs. 6. Relationships of the integrated muscle activity between the Di and Gg and between the Di and Gh were significant, whereas those between the Ma and Sg and between the Ma and Sh were not. 7. When a small strip of polyurethane form of various degrees of hardness was inserted between the opposing molars during CRJTMs, EMG activity of the muscles of group 2 increased with the hardness of the strip. On the other hand, EMG activities of the muscles of group 1 were less affected by the same intraoral stimuli. 8. Two conclusions were reached: first, physiological properties of the CRJTMs and cortically induced rhythmic movements of the hyoid were essentially similar to those observed in natural mastication. This fictive mastication might thus be regarded as a suitable model for simulating natural mastication.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8459288 TI - Trigeminal premotor neurons in the bulbar parvocellular reticular formation participating in induction of rhythmical activity of trigeminal motoneurons by repetitive stimulation of the cerebral cortex in the guinea pig. AB - 1. Single-unit activity was recorded from neurons in the bulbar parvocellular reticular formation (PCRF) dorsal and dorsolateral to the gigantocellular reticular nucleus near its caudal boundary, and the roles of these reticular neurons in induction of rhythmical activity of trigeminal motoneurons by repetitive stimulation of the cerebral cortex (the cortical masticatory area, CMA) were studied in the paralyzed guinea pig anesthetized with urethan or with ketamine and chlorpromazine. 2. One hundred nine PCRF neurons were activated antidromically by microstimulation in either the masseter (MA) or anterior digastric (AD) motoneuron pool in the ipsilateral trigeminal motor nucleus, and orthodromically by stimulation in the contralateral CMA. Repetitive CMA stimulation induced rhythmical burst activity in these PCRF neurons in association with the rhythmical field potential in the contralateral AD motoneuron pool induced by the same CMA stimulation. The burst was synchronous with the rhythmical AD field potential in 81 neurons, 44 and 37 of which responded antidromically to stimulation in the MA and AD motoneuron pools, respectively. The remaining 28 neurons antidromically responded to stimulation in the MA motoneuron pool, and their burst corresponded in time with the period between successive AD field potentials. 3. Spike-triggered averaging of the intracellular potentials of MA and AD motoneurons (MNs) by simultaneously recorded spontaneous spikes of the PCRF neurons, which showed rhythmical burst responses during the jaw-opening phase to repetitive CMA stimulation, revealed a monosynaptic inhibitory postsynaptic potential in MA.MNs in 12 of 34 tested pairs and a monosynaptic excitatory postsynaptic potential (EPSP) in AD.MNs in 14 of 26 tested pairs. An EPSP was also found in MA.MNs after a monosynaptic latency from triggering spikes in 11 of 37 tested PCRF neurons that showed burst activity during the jaw-closing phase. 4. We conclude that both excitatory and inhibitory premotor neurons projecting to MA.MNs as well as excitatory premotor neurons projecting to AD.MNs are located in the PCRF, and that these premotor neurons relay the output of the central rhythm generator for rhythmical jaw movements in the medial bulbar reticular formation to trigeminal motoneurons, and thus participate in induction of rhythmical activities of trigeminal motoneurons by repetitive CMA stimulation. PMID- 8459289 TI - Neural correlates of olfactory learning paradigms in an identified neuron in the honeybee brain. AB - 1. Sensitization and classical odor conditioning of the proboscis extension reflex were functionally analyzed by repeated intracellular recordings from a single identified neuron (PE1-neuron) in the central bee brain. This neuron belongs to the class of "extrinsic cells" arising from the pedunculus of the mushroom bodies and has extensive arborizations in the median and lateral protocerebrum. The recordings were performed on isolated bee heads. 2. Two different series of physiological experiments were carried out with the use of a similar temporal succession of stimuli as in previous behavioral experiments. In the first series, one group of animals was used for a single conditioning trial [conditioned stimulus (CS), carnation; unconditioned stimulus (US), sucrose solution to the antennae and proboscis), a second group was used for sensitization (sensitizing stimulus, sucrose solution to the antennae and/or proboscis), and the third group served as control (no sucrose stimulation). In the second series, a differential conditioning paradigm (paired odor CS+, carnation; unpaired odor CS-, orange blossom) was applied to test the associative nature of the conditioning effect. 3. The PE1-neuron showed a characteristic burstlike odor response before the training procedures. The treatments resulted in different spike-frequency modulations of this response, which were specific for the nonassociative and associative stimulus paradigms applied. During differential conditioning, there are dynamic up and down modulations of spike frequencies and of the DC potentials underlying the responses to the CS+. Overall, only transient changes in the minute range were observed. 4. The results of the sensitization procedures suggest two qualitatively different US pathways. The comparison between sensitization and one-trial conditioning shows differential effects of nonassociative and associative stimulus paradigms on the response behavior of the PE1-neuron. The results of the differential conditioning procedure reveal that the effect observed for the one-trial conditioning paradigm is of an associative nature and that there might be modulations, which are specific for single and multiple trial conditioning procedures. It is hypothesized that the PE1-neuron is a possible element involved in the short-term acquisition, rather than in the long-term storage, of an associative olfactory memory in the honeybee. PMID- 8459291 TI - Down-regulation of protein kinase C and kinase inhibitors dissociate short- and long-term enhancement produced by one-trial conditioning of Hermissenda. AB - 1. The visual system of Hermissenda has been studied extensively as a site of cellular plasticity produced by classical conditioning. Previous research has shown that one-trial conditioning, consisting of light paired with serotonin (5 HT) results in short- and long-term enhancement of light-elicited generator potentials in identified type B-photoreceptors. Recent evidence suggests that 5 HT exerts its effects on the induction of short-term enhancement by activation of protein kinase C (PKC), a Ca(2+)-activated and phospholipid-dependent protein kinase. However, the contribution of protein kinases in general, and specifically PKC in long-term enhancement has not been established. 2. The protein kinase inhibitors H-7 and sphingosine blocked the induction of short-term enhancement when applied before one-trial conditioning. However, the conditions that are sufficient to block the induction of short-term enhancement do not block long term enhancement. Sphingosine and H-7 do not block the induction and expression of long-term enhancement when applied before one-trial conditioning. 3. Pretreatment before conditioning with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), which leads to down-regulation of PKC, also did not block long-term enhancement. Down-regulation by itself did not produce enhancement, although the transient peak of light-elicited generator potentials was reduced by pretreatment with TPA. 4. The results suggest that the induction of short- and long-term enhancement involve parallel processes, and thus the expression of long-term cellular plasticity produced by one-trial conditioning does not depend on the induction or expression of short-term enhancement. PMID- 8459290 TI - Cholinergic modulation of synaptic inhibition in the guinea pig hippocampus in vitro: excitation of GABAergic interneurons and inhibition of GABA-release. AB - 1. The effect of cholinergic receptor activation on gamma-aminobutyric acid (GABA)-mediated inhibitory synaptic transmission was investigated in voltage clamped CA1 pyramidal neurons (HPNs) in the guinea pig hippocampal slice preparation. 2. The cholinergic agonist carbachol (1-10 microM) induced a prominent and sustained increase in the frequency and amplitudes of spontaneous inhibitory postsynaptic currents (IPSCs) in Cl(-)-loaded HPNs. The potentiation of spontaneous IPSCs was not dependent on excitatory synaptic transmission but was blocked by atropine (1 microM). 3. Monosynaptically evoked IPSCs were reversibly depressed by carbachol (10 microM). 4. The frequency of miniature IPSCs recorded in the presence of tetrodotoxin (0.6 or 1.2 microM) was reduced by carbachol (10 or 20 microM) in an atropine-sensitive manner. 5. We conclude that, while cholinergic receptor activation directly excites hippocampal GABAergic interneurons, it has, in addition, a suppressant effect on the synaptic release mechanism at GABAergic terminals. This dual modulatory pattern could explain the suppression of evoked IPSCs despite enhanced spontaneous transmission. PMID- 8459292 TI - Properties of superior vestibular nucleus neurons projecting to the cerebellar flocculus in the squirrel monkey. AB - 1. Properties of superior vestibular nucleus (SVN) neurons and their projection to the cerebellar flocculus were studied in alert squirrel monkeys by using chronic unit and eye movement recording and microstimulation techniques. Twenty three cells were antidromically activated from the ipsilateral flocculus, and seventeen of these were also orthodromically activated from the ipsilateral VIIth nerve at monosynaptic latencies. Only 1 of these 23 units was also inhibited by flocculus stimulation. According to their response properties, 9 of the cells were pure vestibular, 2 were vestibular-pause, and 12 were position-vestibular cells. The mean eye position sensitivity of these position-vestibular cells was significantly lower than that of cells projecting to the oculomotor nucleus (OMN). No eye movement-only neurons were antidromically activated from the flocculus. No cells could be antidromically activated from both the oculomotor nucleus and the flocculus. PMID- 8459293 TI - How surrounds affect chromaticity discrimination. AB - Chromatic discrimination thresholds were measured with and without surrounds along two cardinal axes of chromaticity space. On one axis the level of short wavelength-sensitive (SWS)-cone excitation was varied for constant long wavelength-sensitive (LWS)-cone and medium-wavelength-sensitive (MWS)-cone excitations, and on the other axis there were equal and opposite changes in LWS cone and MWS-cone excitations for constant levels of SWS-cone excitation. Results for two of three observers showed that with a dark surround, discrimination mediated by SWS cones was regulated by the level of SWS-cone excitation of the starting chromaticity, showing a function with the form of a threshold-versus radiance function. For an equiluminant white or yellow surround, the discrimination for all three observers showed a minimum at the level of SWS-cone excitation of the surround, giving a V-shaped function for the white surround. An additional experiment with dimmer white surrounds indicated that while the minimum remained at the white point, the function gradually changed toward the shape with a dark surround. Discrimination thresholds mediated by LWS and MWS cones with a dark surround showed a minimum near the LWS-cone excitation of equal energy white, giving a V-shaped function. The effect of yellow and white surrounds was to deepen the V. The data can be described by a model of chromatic discrimination incorporating a threshold term, a cone gain control, and an opponent gain control into two equations, one for SWS-cone discrimination and one for LWS-cone and MWS-cone discrimination. PMID- 8459294 TI - Fixation of transforaminal sacrum fractures: a biomechanical study. AB - A transforaminal fracture of the sacrum usually represents the posterior part of an unstable pelvic ring fracture and is associated with a high rate of neurological complications. Nerve root decompression combined with open reduction and internal fixation (ORIF) can be beneficial. Present fixation methods have the disadvantage of extensive bilateral posterior approaches and fixation across the sacroiliac joint. Three methods of internal fixation of the sacrum were compared in a biomechanical study using six fresh pelvic specimens. A fracture model consisting of a transforaminal osteotomy combined with a symphysis disruption in a single-leg stance was used. Standard Harrington sacral bars, an internal fixator, and a newly developed stabilization technique using adapted standard AO/ASIF small-fragment implants ("local osteosynthesis") were compared. Three dimensional measurement of the fragment movement (goniometer system) showed a maximum displacement of 4.0-4.5 mm after maximal loading (990-1,181 N) and no differences among the implants. The failure load related to body weight was 85% for sacral bars, 74% for the local osteosynthesis, and 58% for the internal fixator. Major displacement under loading was observed in the direction of the foramen axis. The new osteosynthesis technique showed strength comparable to the clinically successfully applied method of stabilization with sacral bars. It adds the theoretical advantage of a minimized approach, without fixation and thus without involvement of the SI joints. PMID- 8459295 TI - Closed interlocking nailing of femoral shaft fractures: assessment of technical complications and functional outcomes by comparison of a prospective database with retrospective review. AB - Although closed interlocking femoral nailing is generally considered to be a difficult but effective procedure, the true incidence of technical complications has not been well documented. Similarly, long-term and functional patient oriented data are limited. We reviewed our experience with an interlocking nail system that was introduced in our institution in October 1987. One hundred and twenty-three patients were retrospectively reviewed with particular attention to technical complications (Group I). A second group of 144 patients with femoral shaft fractures were reviewed prospectively as a part of our Orthopaedic Trauma Outcome Database (Group IIA). In the earlier retrospective group, the technical complications in 123 cases included one distal screw fracture, one broken drill bit left (in situ), one "missed" locking distal screw, and three cases where comminution at the fracture site was increased. In the prospective group of 144 fractures, the technical complications included two "missed" distal locking screws, two broken screws, and one bent nail due to additional secondary trauma. In a third group of 56 patients (Group IIB) selected from Group IIA, an abbreviated functional assessment was performed at a minimum of 12 months postinjury. Of this group, 37% of the patients had pain that was described as related to barometric changes and was either constant or activity related; 39% had some limitation in ability to ambulate or stand. Nine percent had to obtain new employment or seek job modifications. Based on our data we conclude that closed intramedullary nailing can be done at a Level I Trauma Center with relatively few technical complications, but the functional outcomes are not as good as had been previously believed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8459296 TI - Late functional outcome in patients with tibia fractures covered with free muscle flaps. AB - The functional outcome and work capacity of patients treated with a free muscle flap to cover open grade III tibial fractures was assessed. The conditions of patients, eight with grade IIIB and six with grade IIIC isolated open tibia fractures, treated with a free muscle flap transfer less than 3 months after their injury, were retrospectively reviewed. Flap survival was 86%. Twelve of the 14 were contacted, with follow-up time averaging 7 years. Four of the 14 eventually had below-knee amputations and one of the 10 patients with a successful limb salvage died of unrelated causes. All nine surviving patients with salvaged limbs had healed fractures in an average of 15 months (range, 8 23). Six were initially infected, but drainage had stopped an average of 13.5 months after flap coverage. No wounds were draining at last follow-up observation. Those tibias that were initially infected have been drainage free for an average of 78 months. The average total hospital cost of reconstruction was $48,996.40. The functional outcome in 12 patients was assessed. Eight of the nine patients whose limbs were salvaged returned to work, six to jobs with demands similar to their preinjury occupation. Three of the four patients with limb amputations were also able to return to jobs similar to their preinjury occupation. Patients must be made aware of the expected course of reconstruction and anticipated final outcome. Despite rarely achieving normal function, returning to work is a reasonable goal. PMID- 8459297 TI - Ipsilateral tibia and ankle fractures. AB - This study reports on 18 cases of diaphyseal fractures of the tibia associated with ipsilateral but not contiguous ankle fractures. Thirteen of these complex fractures resulted from low-energy torsional forces, while five were caused by high-energy impact. Definitive treatment consisted solely of cast immobilization in four; 14 had operative stabilization of each fracture component. Of these 14, four patients were treated initially in long leg casts and one in a plaster splint, but each required surgical intervention to control fracture alignment. The average follow-up time was 21.2 months. In the nonoperative group of four patients, clinically significant shortening and/or rotational deformity were noted in three limbs, with ankle mobility decreased by > 50% and advanced posttraumatic arthritis evident in two ankles. Of the cases managed operatively, 10 (71%) had full structural and functional recovery, three patients regained only 75% of ankle mobility, and two patients developed slight valgus deformities, one with a concomitant rotational deformity of less than 10 degrees. These findings demonstrate the unstable nature of this complex fracture pattern and the advantages of operative management. PMID- 8459298 TI - Extraction strength of cannulated cancellous bone screws. AB - The purpose of this study was to determine whether the alterations in the relative dimensions of thread and core diameter that accompany cannulation of cancellous bone screws affect their holding strength. The screws were inserted in bovine femoral cancellous bone and mounted in the load train of a materials testing system. They were then extracted under servo-hydraulic displacement control. The tests were repeated in synthetic cancellous material. From the corresponding load-displacement histories, the maximum force values attained were determined as the screws' holding strengths. The results of tests from 17 matched pairs of bovine femora, and of 15 tests of each screw in synthetic material, were recorded. No significant differences in extraction strength between 7.0-mm cannulated and 6.5-mm standard cancellous bone screws were found. Based on tests in the bovine femur and synthetic cancellous material, this study showed that the extraction strength of cancellous bone screws is not altered by the changes in thread-to-core ratio accommodating cannulation. PMID- 8459299 TI - Mycobacterium fortuitum osteomyelitis following trauma. AB - Consequent to a high-speed motor-vehicle accident, a patient developed Mycobacterium fortuitum osteomyelitis of an open fracture of his proximal humerus. The patient was treated with a single debridement, oral ciprofloxacin, and hyperbaric oxygen and is free of disease at 2 years. PMID- 8459300 TI - Concomitant ipsilateral intertrochanteric and subcapital fracture of the hip. AB - A unique case of coexistent intertrochanteric and subcapital fractures of the hip is presented. A review of the literature found only one previous report of the simultaneous occurrence of these fractures. Closed reduction with in situ pinning was performed. Other treatment alternatives are reviewed and discussed. PMID- 8459301 TI - Double disruptions of the superior shoulder suspensory complex. AB - The superior shoulder suspensory complex (S.S.S.C.), a bony/soft tissue structure, is important both for its role as an intact unit and for the individual components that make up this unit. Traumatic "double disruptions" of the S.S.S.C. frequently create an unstable anatomic situation with adverse long term healing and functional consequences. This "double disruption" principle underlies, unites, and allows one to understand several well-described but difficult-to-treat shoulder injuries that have previously been described in isolation. Injuries to the S.S.S.C. require careful radiologic evaluation for the possible presence of a "double disruption." If displacement is unacceptable, surgical reduction and stabilization of one or more of the injury sites is necessary. PMID- 8459302 TI - [Birch pollen nasal allergy in Sapporo and its cross reactivity with alder pollen]. AB - We reported here 53 cases of birch pollen nasal allergy treated in our department from 1990 to 1991. The 53 patients constituted 16% of 335 total nasal allergy patients. In recent years, the number of birch pollen nasal allergy patients has apparently been gradually increasing in Sapporo. Skin tests, radioallergosorbent test (RAST) determinations and nasal provocation tests were performed for the diagnosis of birch pollen nasal allergy, and high degrees of correlation were observed among these tests. Therefore, it seems to be reasonable to determine the birch pollen allergy with only a positive case history of early springtime hay fever and RAST determination. A high correlation coefficient (Rho) value was found with RAST determinations between birch pollen and alder pollen. Furthermore, RAST of alder pollen was significantly inhibited by birch pollen extracts. These results indicate cross reactivity, presumably due to partial immunologic identity between these two pollen allergens. PMID- 8459303 TI - [The effect of calcium ion on ampullary nerve potential]. AB - The effect of calcium ion (Ca2+) in the endolymphatic and/or perilymphatic space of the posterior semicircular canal (p.s.c.) nerve response was studied. When both endolymph and perilymph contained no Ca2+, no p.s.c. nerve response was observed. When only the endolymph contained Ca2+ and the perilymph was Ca2+ free, again no nerve response was observed. On the other hand, when only the perilymph contained Ca2+, p.s.c. nerve response was evoked. Therefore, Ca2+ in the perilymph was considered to be essential for maintaining the function of the p.s.c. as a mechanoreceptor. PMID- 8459304 TI - [Fine needle aspiration cytology under ultrasonographic imaging]. AB - Although fine needle aspiration cytology (FNA) is widely used in the otolaryngology, few hospitals perform it in conjunction with ultrasonographic imaging. Despite the benefits of ultrasonographic imaging-assisted FNA, it is not widely utilized due to the prevalent misperception that the procedure is exceedingly complicated. In an effort to refine FNA procedures under ultrasonographic imaging (focusing on safety and simplification), we conducted a study on outpatients with neck tumors. We developed the following guidelines. 1. The aspiration was conducted free-hand without the use of mechanical devices such as special probes and/or aspiration adaptors. 2. Positioning of the probe was adjusted so that the puncture site was centered in the image. 3. When the tumor was located near the carotid artery or jugular vein, the probe was adjusted so that both the tumor and the blood vessel could be observed in the same image. 4. The needle was introduced at the center of the probe from the sliced direction. The needle injection route was then adjusted in line with phase crossing at right angles with the scanning field of the probe. 5. The depth of the puncture was adjusted in accordance with the angles between the probe and the needle. From June 1985 to December 1990, FNA under ultrasonographic imaging was conducted on 149 patients. It was possible to compare both cytological and histological studies. According to site, lymph nodes ranked highest in 52 cases, followed by parotid glands (45) and thyroid glands (27). A 5 or 7.5 MHz probe was used with 21- or 22-gauge injection needles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8459305 TI - [Hearing distribution of idiopathic bilateral sensorineural hearing loss]. AB - We investigated the mode of progression of idiopathic bilateral sensorineural hearing loss diagnosed in patients seen in the Hearing Loss Clinic at the Department of Otolaryngology of Kitasato University Hospital. Entered into the study were 105 patients whose courses could be observed for more than 3 years. Audiograms were taken 1069 times in these 105 patients and were examined with regard to the distribution of hearing levels by frequency. Idiopathic bilateral sensorineural hearing loss was divided into three stages from the aspect of the time of hearing change stages I, II and III. Hearing clustering points of the respective stages were compared with each other. Proceeding from the peak of stage I to that of stage II was found to take place at the same peak as that of stage III. Another peak hearing clustering point was noted at s.o.. PMID- 8459306 TI - [Cochlear nerve conduction block restoration of hearing after removal of cerebellopontine tumors]. AB - Hearing restoration after removal of cerebellopontine tumors has only infrequently been observed. We present 5 cases with dramatic improvement of both pure tone threshold and speech threshold after excision of tumors. Two patients had acoustic neuroma, 2 meningioma and one cerebellar hemangioblastoma. Preoperatively, the patients suffered severe sensorineural hearing loss and had no measurable speech discrimination score. Recordings of the auditory brain stem response were absent or showed only wave I. However, results of the electrocochleogram were within normal limits. After removal of the tumors, their hearing returned to normal and remained stable thereafter. The data are consistent with the hypothesis that pressure from the tumor causes cochlear nerve conduction block and hearing impairment. PMID- 8459307 TI - [Association of Chlamydia pneumoniae infection with otitis media with effusion]. AB - Chlamydia pneumoniae has recently been recognized to cause various human respiratory tract diseases, including pharyngitis, bronchitis and pneumonia. The most common pathogens of respiratory tract infections such as Streptococcus pneumoniae and Haemophilus influenzae are frequently present in middle ear effusions. Therefore, it is possible that C. pneumoniae play a role in otitis media with effusion (OME). Isolation of C. pneumoniae from middle ear aspirates of OME was performed by the culture method using the HeLa 229 or HL cell line. Identification as C. pneumoniae was based on positive staining for inclusions by a species-specific fluorescein-conjugated monoclonal antibody. C. pneumoniae was recovered from 17.8% (13 of 73) of the patients with acute OME, and 7.1% (3 of 42) of those with chronic OME, Moreover, antibodies to C. pneumoniae were measured by the microimmunofluorescence method in 14 patients who yielded the agent, and all of them had detectable antibodies to C. pneumoniae. Evidence of recent or current infection by the organism was found in nine patients on the basis of either on IgM antibody titer of 1:16 or higher, or a four-fold rise in the titer of IgG antibody. The study findings indicate that C. pneumoniae can cause OME and that the organism is a new candidate as an etiological agent of middle ear diseases. PMID- 8459308 TI - [Study on human diseased thyroid cells in collagen gel culture--morphology and their malignancy of cultured colonies]. AB - Thyroid cells from 14 normal subjects, two patients with Grave's disease, four patients with follicular adenoma and eight patients with papillary carcinoma were cultured in collagen gel. The colonies of these cells were stereoscopically observed and their morphological characteristics were studied with regard to relation with pathological findings of mother tumor, extra-capsular invasion and metastatic potential. For normal thyroid, Grave's disease and follicular adenoma (except for one case), their own characteristic branching type colonies were found. For papillary carcinoma, both branching type and spheroid type of colonies were observed. The ratio of branching type/spheroid type varied individually in the patients with papillary carcinoma. However, the spheroid type was found to trend to be predominant in patients with extra-capsular invasion and/or lymph node metastasis. This means that the observation of spheroid type colonies in collagen gel is suggestive of risk of extra-capsular invasion or lymph node metastasis. From the obtained results, it seemed possible to diagnose poorly differentiated cells in vitro by morphologically observing colonies of human thyroid papillary carcinoma cells developing in collagen gel. PMID- 8459309 TI - [Tissue culture of guinea pig middle ear epithelium--morphological characterization and proliferative activities of cultured cells on fibroblast reorganized collagen gels]. AB - Long-term culture of the middle ear epithelium of guinea pigs was carried out on reconstituted floating collagen matrix. Fibroblasts established from the abdominal skin dermis of allogenic animals were used to reorganize hydrated collagen gels into a dermal-like matrix. The explants placed on the surface of these matrices were composed of pseudostratified columnar cells with polygonal flat outgrowth sheets, which could be maintained for up to one month. In contrast, with simple hydrated collagen gel, no lysis of the substrate was observed regarding this reorganized collagen gel. In order to examine the growth pattern of these culture cells, 5-bromodeoxyuridine (BrdU) was added to the medium during the entire culture period. The specimens were immunohistologically stained using monoclonal antibodies. Noticeable changes were observed in the marginal portion of the explant where the cell shape changed from cuboidal to squamous. In this transitional area, most cells showed positive staining and consequently high proliferative activity. In the central area of the explants, however, the number of positive cells decreased and the main observation was a few labeled basal cell nuclei. It was suggested that the same regenerative process which usually occurs in normal respiratory epithelia after mechanical injury or other insults, was replayed in this culture system. PMID- 8459310 TI - [Disorder of swallowing muscles in iron deficient rabbits]. AB - Plummer-Vinson syndrome is a clinical entity associated with dysphagia, sideropenic anemia and atrophic glossitis. Using rabbits with iron deficiency anemia, the author investigated the cause of dysphagia in this syndrome. Iron deficient animals were produced by bolus feeding without iron and intramuscular injection of an iron-chelating agent. The fibers of swallowing muscles (the thyro pharyngeal, cricopharyngeal and cervicoesophageal muscles) were classified into three types (Type 1, 2A and 2B fibers) by actomyosin ATPase staining. No significant difference between the muscles of sideropenic rabbits and those of normal rabbits were found in the composition and distribution of their muscle fibers. By NADH-TR staining, however, the disturbance of the intermyofibrillar network and/or a "Moth Eaton" appearance, known to be caused by leakage of mitochondria, were observed in Type 1 fibers of the swallowing muscles of sideropenic rabbits. These morphological changes are similar to those observed in progressive muscular dystrophy. The quantity of iron in the swallowing muscles of sideropenic rabbits was significantly reduced in comparison with that in the sternothyroid and femoral muscles. This finding suggests that a selective decrease in myoglobin occurs in the swallowing muscles of iron deficient animals. From these observations, it might be concluded that dysphagia in iron deficiency anemia is caused by a myogenic disorder. PMID- 8459311 TI - [Statistical analysis on the cases of thyroid papillary carcinoma]. AB - Statistical analysis was performed on the postoperative recurrence of forty four patients with thyroid papillary adenocarcinoma, who underwent radical surgery in the Department of Otolaryngology, Hamamatsu University Hospital from January 1978 to March 1991. In this study, we defined a new factor called "Operative Radicality index (OR index)" and analyzed the data with a multivariate analysis (Cox model). The result showed that the risk of postoperative recurrence was significantly affected by the age, the size of tumor and the OR index. The postoperative five-year cumulative recurrence rate was approximately 10% in the group of patients whose lateral neck regions were systematically dissected only when any metastatic lymph nodes were clinically detected within the region, in addition to the routine anterior neck dissection, and 70% in the group of patients whose metastatic lymph nodes in the lateral neck region were partially removed, but 6% in the group of N0 patients who did not undergo lateral neck dissection because no nodal metastases were detected even in the operative findings. Considering the quality of postoperative life, we concluded that in the primary surgery for the thyroid papillary adenocarcinoma, the lateral neck dissection should be applied to only the regions with metastatic nodes detected preoperatively or during operation, in addition to the routine anterior neck dissection. And the OR index was useful for the statistical analysis with regard to the policies of treatment and the prognosis. PMID- 8459312 TI - [Autonomic neurons sending fibers into the canine laryngeal nerves--using a retrograde tracer technique with cholera toxin]. AB - The distribution of the autonomic neurons sending fibers into the canine superior and inferior laryngeal nerves was investigated by an immunohistochemical technique with cholera toxin B subunit as a retrograde tracer. Cholera toxin was applied to the right internal branch of the superior laryngeal nerve (SLNI), external branch of the superior laryngeal nerve (SLNE) or inferior laryngeal nerve (ILN) in 2-month-old dogs. In every case of cholera toxin application, labeled neurons were seen mainly in the caudal portion of the ipsilateral superior cervical ganglion, whereas none were seen in the stellate ganglion. The number of labeled neurons in the superior cervical ganglion after application of cholera toxin to the SLNI was over 20 times that observed after application to the SLNE or ILN. When cholera toxin was applied to the SLNI or SLNE, labeled neurons were found mainly in the ipsilateral dorsal motor nucleus of the vagus (DMNV), and a few labeled neurons were found in the ipsilateral reticular formation. The neurons in the DMNV were localized, on the average, between 2.7 mm and 5.3 mm rostral to the obex. The number of neurons in the DMNV labeled retrogradely from the SLNI was much larger than that from the SLNE. In contrast, no labeled neurons were detected in the DMNV after application to the ILN. These results demonstrate the following: 1) The sympathetic neurons innervating the canine larynx are distributed mainly in the caudal portion of the superior cervical ganglion and they send their fibers mainly into the SLNI. 2) The parasympathetic neurons innervating the canine larynx have a limited distribution in the dorsal motor nucleus of the vagus and their main pathway is also the SLNI. PMID- 8459313 TI - [Expression of HLA-DR antigen on head and neck carcinomas--immunohistological study]. AB - We investigated the expression of HLA-DR antigen on 42 squamous cell carcinomas of head and neck using immunohistological methods. Our results indicate significant relationships between HLA-DR antigen expression on carcinomas and lymphocytic infiltration, that is, CD8 positive lymphocytes (CD8/CD3) infiltrated HLA-DR antigen positive carcinomas while CD4 positive cells (CD4/CD3) were found in HLA-DR negative carcinoma. The Ki-67 (a nuclear marker of proliferation) positive rate was lower on HLA-DR positive carcinomas than on negative carcinomas. However, there was no correlation with pathological differentiation, clinical stage or primary lesion. In vitro studies using several cytokines showed that IFN-gamma induced expression of HLA-DR antigen and lowered the Ki-67 positive rate on squamous cell carcinomas. It seems that HLA-DR antigen expression on squamous cell carcinomas could be induced by cytokines released from the infiltrating lymphocytes. PMID- 8459314 TI - [Biochemical profile of proteoglycans and glucosaminoglycans of the mammalian tectorial membrane]. AB - The tectorial membrane is an acellular connective tissue which plays an essential role in cochlear function. While a comparatively large amount of information is available on the collagen network of the tectorial membrane, studies on the biochemical nature of this highly hydrated matrix, which is composed of proteoglycans (PGs) and glycosaminoglycans (GAGs), have been quite limited. Previous reports on the biochemical analysis of the tectorial membrane have failed to detect uronic acid, which is present in large amounts in all mammalian GAGs except keratan sulfate. Applying a colorimetric assay based on the binding of GAGs to cationic dye Safranin-0 in combination with enzymatic techniques, we were able to measure GAGs in the murine tectorial membrane. Approximately 0.3% uronic acid-containing GAGs (mainly in the form of chondroitin/dermatan sulfate) and 0.17% keratan sulfate were detected in the tectorial membrane (both on a wet weight basis). In addition, various types of electrophoresis revealed one large PG with a molecular mass similar to that of the large type cartilage PGs and three small PGs, containing chondroitin sulfate and keratan sulfate side chains, respectively. Judging by coelution of standards, one of the small PGs seemed to correspond to fibromodulin, which has at least one keratan sulfate side chain, and binds to type I and type II collagen to regulate collagen organization in tissues. Our results suggest: (1) Donnan equilibrium is established in the tectorial membrane because sulfated GAGs are highly negatively charged and consequently bring about an influx of large amounts of water and cations into the matrix.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8459315 TI - Photodynamic effects on the nuclear envelope of human skin fibroblasts. AB - Photodynamic effects on the nuclear envelope of human skin fibroblasts were investigated by confocal laser fluorescence microscopy and transmembrane resting potential measurements. The results show staining of the nuclear envelope after short incubation times with Photosan III, Photofrin II and haematoporphyrin derivative (HPD) enriched with monomers. Maximum staining was found at the centre of the nuclear envelope. The sequence of fluorescence intensity was HPD enriched with monomers > Photofrin II > Photosan III. After lethal treatment with Photosan III and tetrasulphonated aluminium chloride phthalocyanine, the nuclear transmembrane potential of the nuclear membrane decreased from -20 mV to about 10 mV with reference to the plasma membrane potential. PMID- 8459316 TI - Photoinduced interaction of Ru(bpy)3 2+ with nucleotides and nucleic acids in the presence of S2O8 2-; a transient conductivity study. AB - The photochemical reactions of Ru(bpy)3(2+) with single- and double-stranded DNA, polynucleotides and purine-containing nucleotides in argon-saturated aqueous solution in the presence of S2O8(2-) were studied using time-resolved absorption and conductivity methods. The conversion of Ru(bpy(3(3+) to Ru(bpy)3(2+), monitored spectroscopically either after rapid mixing with substrate or after laser flash excitation (lambda exc = 353 nm) is quantitative at nucleotide-to sensitizer ratios [N]/[S] of 1-2 for DNA and other guanine-containing compounds. Conductivity measurements following the laser pulse revealed a fast conductivity increase (rise time, less than 0.1 ms) due to the formation of protons and, to a lesser degree, to charged species of much lower ion mobility. A slower component in the 0.01-1 s range was observed for nucleic acids; its amplitude is markedly reduced at pH 6-9. In buffered neutral solution the signal is replaced by a slight decrease in conductivity. Electronically excited Ru(bpy)3(2+) bound to DNA reacts with S2O8(2-) to form Ru(bpy)3(3+) and SO4(.-) as primary oxidizing species both of which react with bases. The resulting base radicals react subsequently with Ru(bpy)3(3+) and Ru(bpy)3(2+) or the ligands in the ruthenium complex, producing protons which give rise to the slower conductivity increase. The formation of single-strand breaks and the ensuing release of condensed counterions does not appear to contribute significantly to the slow component. The transient conductivity behaviour is sensitive to the single- or double stranded nature of DNA. PMID- 8459317 TI - Photosensitizing properties of mono-L-aspartyl chlorin e6 (NPe6): a candidate sensitizer for the photodynamic therapy of tumors. AB - There is a large amount of interest in chlorins as photosensitizers for the photodynamic therapy of tumors because of their strong absorption in the red, where light penetration into mammalian tissues is efficient. Mono-L-aspartyl chlorin e6 (NPe6), in phosphate buffer of pH 7.4, had absorption peaks at 400 and 654 nm with molar absorption coefficients of 180,000 and 40,000 M-1 cm-1 respectively. In buffer, the NPe6 triplet had a peak at 440 nm and a lifetime under argon of approximately 300 microseconds. The triplet was efficiently quenched by ground state oxygen (kQ = 1.9 x 10(9) M-1 s-1) with the formation of singlet oxygen, as identified by its near infrared luminescence. The quantum yield of singlet oxygen production was 0.77. A number of substrates were efficiently photo-oxidized by NPe6, including furfuryl alcohol, cysteine, histidine, tryptophan and human serum albumin. These reactions were efficiently inhibited by azide (which did not quench NPe6 triplets), indicating that they are probably mediated by singlet oxygen. Thus, NPe6 has a desirable array of photoproperties for a sensitizer to be used in the clinical photodynamic therapy of tumors. PMID- 8459318 TI - Evaluation of the quantum yield for E-->Z isomerization of bilirubin bound to human serum albumin. Evidence of internal conversion processes competing with configurational photoisomerization. AB - The quantum yield (phi zz) for the E--> photoisomerization of bilirubin (BR) bound to human serum albumin (HSA) under laser light irradiation has been evaluated with absorbance spectroscopy implemented by the high-performance liquid chromatography technique. The value at 458 nm is about 0.2, four times smaller than the value previously reported in the literature. As for the Z-->E configurational and the structural photoisomerization processes, the quantum yield varies with excitation wavelength, from 0.23 in the blue to 0.16 in the green. The sum of the quantum yields of the Z<-->E configurational photoisomerization reactions is 0.2-0.3 in the blue-green spectral region, thus giving direct evidence of the existence of internal conversion processes of the BR-HSA complex which compete with configurational photoisomerization. An evaluation of the quantum yields of the Z<-->E reactions for filtered broad-band light excitation in the 390-530 nm spectral region from data already published in the literature is also reported. Good agreement with our data of the quantum yields phi ZZ and phi ZE is found, despite the diversity of the experimental procedures in the two cases. PMID- 8459319 TI - Photophysical properties of the photosensitizer pheophorbide a studied at high photon flux densities. AB - The photophysical properties of pheophorbide a (Pheo a) under two-step laser activation were investigated. For the first time quantum yields of higher excited state formation were calculated. It was shown that the quantum yields of the formation of these states depend strongly on the pulse duration of the excitation source. The nonlinear properties of Pheo a are quite different in dependence on the excitation wavelength but the quantum yields of the higher excited state formation in both cases (lambda exc = 337 nm and lambda exc = 667 nm) rise up increasing the photon flux density of the laser light up to 10(26) phot cm-2 s-1. A further increase of the photon flux density has no effect on the quantum yields. PMID- 8459320 TI - Sensitivity of different rat tumour strains to photodynamic treatment with chlorin e6. AB - Transplantable rat tumours (sarcoma M-1, sarcoma 45, alveolar liver cancer PC-1 and Pliss' lymphosarcoma) were used to study chlorin e6 accumulation in tumours and its photodynamic effect. Tumours were irradiated by krypton ion laser light (647 and 676 nm; 90 J cm-2) 15 min and 24 h after chlorin e6 injection at doses of 5 and 10 mg kg-1. The relationship between some morphological peculiarities of these tumour strains, photosensitizer accumulation in tumours and their response to the photodynamic treatment is discussed. PMID- 8459321 TI - A photobiological evaluation of lamps used in the phototherapy of seasonal affective disorder. PMID- 8459322 TI - Photosensitizers as virucidal agents. AB - The photosensitizer, benzoporphyrin derivative monoacid ring A (BPD-MA) has been studied regarding its ability to destroy enveloped viruses in blood and blood products when activated by light. Its maximum wavelength of absorption (690 nm) has proven useful in terms of activation of the photosensitizer in materials containing red blood cells. Experiments conducted on whole blood of patients infected with the human immunodeficiency virus (HIV) demonstrated that BPD-MA and light could effectively eliminate the virus when treated materials were placed in culture and tested for viral p24, but did not appear to damage blood cells or blood components. Since HIV is largely intracellular in infected individuals, these results were investigated further. We have shown, using flow cytometry, that in HIV-infected blood, BPD-MA and light appear to selectively destroy white cells that bear the interleukin 2 receptor and the DR antigen. These markers are prevalent on activated lymphocytes, and since HIV replicates only in CD4+ T cells which are activated, this finding provides an explanation for the selective killing of HIV. PMID- 8459323 TI - A trap for the detection of schistosome cercariae. AB - A simple trap for schistosome cercariae has been developed using clear nail varnish as a matrix and linoleic acid as stimulant affixed to a 75 x 25-mm glass slide. Schistosoma mansoni cercariae will attach to the surface and easily can be visualized either stained or unstained. The trap works well under laboratory and field conditions where the retrieval rate varies from 30% to 100%. Under laboratory conditions there appears to be some form of affinity for cercariae to the surface. PMID- 8459324 TI - The occurrence of phenol oxidase activity in female Trichuris suis. AB - The body of Trichuris suis females maintained in vitro under a gas phase of 95% air 5% CO2 develops a brown pigment that is apparent after 1 day and intensifies with time. Development of the brown pigment is prevented by maintaining the parasites in an anaerobic gas phase (95% N2, 5% CO2), but tanning commences when worms are returned to aerobic conditions. Tanning was not observed in males. Intact female T. suis take up oxygen at a considerably higher rate than males. Supernatant fractions (10,000 g) and pellets from whole worm homogenates of females both convert dihydroxyphenylalanine (DOPA) to dopachrome, suggesting the presence of a phenol oxidase. About 70% of the total phenol oxidase activity in females was in the pellet and about 30% in the supernatant fraction. Homogenates of male worms contained minimal phenol oxidase activity. Polarographic assay of phenol oxidase activity confirmed the presence of this enzyme in female T. suis. Female homogenates oxidized both dihydroxyphenylalanine and 4-methylcatechol and to a lesser extent hydroquinone. This oxidation was inhibited (> 90%) by diethyldithiocarbamate. Males did not oxidize any of the substrates tested. These results suggest that an enzyme of the phenol oxidase type is present in female worms but is probably inactive because of low oxygen tensions in the swine colon. The function of this enzyme in T. suis is unknown but is most likely associated with tanning of eggshell proteins or other aspects of eggshell synthesis. PMID- 8459325 TI - Synthesis of tyrosine-derived cross-links in Ascaris suum cuticular proteins. AB - Tritiated dityrosine and isotrityrosine were detected by high performance liquid chromatography (HPLC) of acid hydrolysates of cuticular proteins from larval Ascaris suum following their 96-hr in vitro incubation in [3H]tyrosine. Sixty percent of the HPLC-recovered radiolabel was present as tyrosine, 20% as dityrosine, and 6% as isotrityrosine. Approximately 13% of radioactivity was associated with several unidentified peaks. A similar distribution of radioactivity was observed in acid hydrolysates of cuticular proteins from young adults of A. suum following 48 hr in vitro incubation with [3H]tyrosine. The 2 mercaptoethanol (2ME)-insoluble cuticular protein from the larval stages had a higher rate of synthesis of [3H]dityrosine than did the 2ME-soluble cuticular proteins, whereas the 2ME-soluble cuticular proteins had higher rates of synthesis of [3H]isotrityrosine. Pulse-chase studies of A. suum larvae demonstrated a relatively low rate of synthesis of both dityrosine and isotrityrosine. The addition to the culture media of the peroxidase inhibitors, phenylhydrazine (PHEN), 3-amino-1,2,4-triazole (AT), and N-acetyltyrosine (NAT) reduced the amount of [3H]tyrosine synthesized into both dityrosine and isotrityrosine. In a cell-free system, soluble extracts of A. suum larvae also converted radiolabeled tyrosine to dityrosine; isotrityrosine was produced by some extracts. The rate of conversion correlated with time of incubation and the volume of added extract and was inhibited by AT, NAT, and PHEN, with PHEN being the most potent inhibitor. The results of the present study suggest that the tyrosine residues of the cuticular proteins are posttranslationally modified by the formation of dityrosine and isotrityrosine cross-links. This modification is most likely mediated by a peroxidase. PMID- 8459326 TI - Glutamine-supported motility of adult filarial parasites in vitro and the effect of glutamine antimetabolites. AB - The survival in culture of adult female Brugia pahangi, Acanthocheilonema viteae, and Onchocerca volvulus and adult male Onchocerca gibsoni was assessed by measuring parasite motility. Survival of all species was maximal in a nutritionally complex medium (RPMI-1640). All species survived for up to 48 hr in a simpler medium in which the only energy source was 10 mM glutamine; motility in this medium was dependent upon pH. For the species of Onchocerca, motility was maintained better in the presence of glutamine as the sole energy source than in glucose-only medium. Motility of B. pahangi incubated in 10 mM succinate was equivalent to that seen with 10 mM glutamine, but no other tricarboxylic acid intermediate supported this parasite in vitro. Antimycin A (1 microM) and potassium cyanide (KCN, 100 microM) paralyzed B. pahangi incubated in 10 mM glutamine, an effect antagonized by glucose. KCN at 10 or 100 microM was effective also against Onchocerca gutturosa in glutamine-only medium. Several glutamine antimetabolites reduced motility of B. pahangi by 72 hr. This inhibition was prevented by 2 mM glutamine. However, the inhibition of motility in the species of Onchocerca caused by these compounds was attenuated only partially by glutamine. These data demonstrate that, under certain conditions, filarial nematodes can utilize non-sugar substrates as energy sources. The differential sensitivity seen among these organisms to mitochondrial toxins and glutamine antimetabolites may be related to the extent to which they can use these alternative substrates to generate energy. PMID- 8459327 TI - Coccidia (Apicomplexa), genetic diversity, and environmental unpredictability of four chromosomal species of the subterranean superspecies Spalax ehrenbergi (mole rat) in Israel. AB - Forty-five mole-rats, representing 4 chromosomal species (2n = 52, 54, 58, 60) of the superspecies Spalax ehrenbergi, were collected from 12 localities in Israel in 4 distinct climatic regions. Feces were examined for coccidian oocysts and 41 (91%) were infected; 26 (63%) had multiple infections of up to 5 coccidian species, 4 of which are described here as new species. Sporulated oocysts of Eimeria anzanensis n. sp. were ellipsoidal 18.3 x 12.5 microns (14-22 x 10-16) and had elongate-ovoidal sporocysts 7.3 x 4.9 microns (5-10 x 3-7); it occurred in 39 of 45 (87%) mole-rats, including all chromosomal species. Sporulated oocysts of Eimeria spalacensis n. sp. were ovoidal 23.4 x 18.3 microns (17-29 x 12-21) with ovoidal sporocysts 9.4 x 6.8 microns (6-12 x 4-10); it occurred in 7 of 45 (16%) mole-rats (2n = 54, 58, 60). Sporulated oocysts of Eimeria carmelensis n. sp. were subspheroidal to ellipsoidal 19.1 x 16.5 microns (14-25 x 11-20) and had sporocysts that were spheroidal to ellipsoidal 8.6 x 6.2 microns (6-13 x 4-8); it occurred in 5 of 45 (11%) mole-rats (2n = 58, 60). Sporulated oocysts of Isospora spalacensis n. sp. were ellipsoidal 14.6 x 11.0 microns (12 17 x 9-14) with ellipsoidal to ovoidal sporocysts 8.5 x 4.5 microns (7.5-11 x 4 7); it occurred in 5 of 45 (11%) mole-rats (2n = 58, 60). Twenty-five of 45 (56%) mole-rats (all 4 species) were infected with a previously described form, Eimeria elliptica Sayin, Dincer, and Meric, 1977.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8459328 TI - Kudoa intestinalis n. sp. (Myxosporea: Multivalvulida) from the intestinal musculature of the striped mullet, Mugil cephalus, from Japan. AB - Kudoa intestinalis n. sp. (Myxosporea: Multivalvulida) is described from the intestinal musculature of the striped mullet, Mugil cephalus, from the southeastern coast of the Kii Peninsula, Japan. The plasmodia of the new species are spherical or ellipsoidal and contain quadrangular spores that, on the average, measure 3.4 microns in length, 6.5 microns in width and 6.1 microns in thickness. The species is characterized by the presence of short projections at the apex and concave values posteriorly. PMID- 8459329 TI - Development and longevity of Nosopsyllus laeviceps kuzenkovi (Siphonaptera) from Inner Mongolia under laboratory conditions. AB - The development and longevity of Nosopsyllus laeviceps kuzenkovi (Yagubyants), a major plague vector among sylvan and campestral rodents in Inner Mongolia, China, was studied under controlled laboratory conditions of 11, 14, 17, 20, 23, 26, 29, and 35 C at 76% relative humidity (R.H.), and 32, 53, 76, 87, and 100% at 23 C. Development from egg to adult was shortest (21-23 days) under favorable conditions of 26 C at 76% R.H., but maximum survival to adulthood (84%) occurred at 23 C. Average longevity was 13.25 days (13.70 in females and 12.80 in males) at 17 C and 76% R.H.; it was longer at cooler and shorter at warmer temperatures. Findings provided experimental data that helped clarify seasonal fluctuations, summer mortality, generation cycles, and survival of compared flea species from Russia, Azerbaidzhan, and China. PMID- 8459330 TI - Uncoupling of rat liver mitochondrial oxidative phosphorylation by the fasciolicide triclabendazole and its sulfoxide and sulfone metabolites. AB - The uncoupling activity of a narrow-spectrum benzimidazole anthelmintic triclabendazole (TCZ, 6-chloro-5-[2,3-dichlorophenoxy]-2-methylthio benzimidazole) and its 2 principal metabolites triclabendazole sulfoxide (TCZ sulfoxide, 6-chloro-5-[2,3-dichlorophenoxy]-2-methylsulfinyl-benzimidazole) and triclabendazole sulfone (TCZ sulfone, 6-chloro-5-[2,3-dichlorophenoxyl] 2methylsulfonyl- benzimidazole) has been determined using rat liver mitochondria. With glutamate or succinate as the mitchondrial substrate, and the respiratory control index (RCI) as an indicator of uncoupling activity, we found that TCZ and its 2 main metabolites were uncouplers of oxidative phosphorylation at micromolar concentrations. The rank order of in vitro activity was TCZ sulfone > TCZ sulfoxide > TCZ. Structure-activity relationship studies revealed that the electron-withdrawing power of the substituent in the 2-position was the principal determinant of mitochondrial uncoupling activity. Correlation techniques were used to assess the strength of the relationship between the ability of TCZ and its metabolites to uncouple oxidative phosphorylation and their ability to lower the electrical resistance of planar bimolecular lipid membranes. A log-log plot of RCI I50 vs. resistance effective concentration (REC I50) gave a linear fit with a correlation coefficient (r) of 0.98; an r of 0.98 indicates a high positive relationship between the ability of these fasciolicides to uncouple oxidative phosphorylation and their ability to lower electrical resistance. These findings are consistent with the view that TCZ and its sulfoxide and sulfone metabolites are lipophilic protonophoric uncouplers of rat liver mitochondrial oxidative phosphorylation. PMID- 8459331 TI - Trematode community structure in the pulmonate snail Physa gyrina. AB - Trematode community structure was examined in the pulmonate snail Physa gyrina over a 12-mo period. A total of 1,181 snails was collected from Charlie's Pond, North Carolina, and was found to be parasitized by 6 trematode species. Infracommunities were relatively species rich when compared to previous studies, with 18.4% of infected snails having multi-species infections. Halipegus eccentricus was found in 88.4% of multiple infections, usually with 1 of 2 other autogenic, egg-transmitted species (Haematoloechus complexus and Glypthelmins quieta). Neither negative interspecific interactions nor a dominance hierarchy were apparent among the trematodes. These factors, along with high snail vagility and the temporal heterogeneity of infective stages in the environment, are suggested to have contributed to the high number of multiple infections. Halipegus eccentricus was also the most prevalent parasite throughout the study, occurring in nearly 50% of all snails during May, June, and July. Apparent parasite-induced host mortality caused by this trematode species contributed to increasing species diversity in larger snails. The component community was also affected by the continuous recruitment of new snails into the host population and by changes in the number of infective stages present over time. PMID- 8459332 TI - Resistance to Schistosoma bovis in sheep induced by an experimental Fasciola hepatica infection. AB - Sheep infected with Fasciola hepatica for 10 wk acquired a substantial level of resistance to challenge with Schistosoma bovis. The worm burden was reduced by 87.2% (P < 0.01) compared with that of a control group. But when sheep primarily were infected with S. bovis and 6 wk later with F. hepatica, no significant reduction in the S. bovis burden was observed. PMID- 8459333 TI - Relationship between human serum trypanocidal activity and host resistance to the African trypanosomes. AB - Results reported here show that humans have various levels of trypanocidal activity in their sera. This difference appeared stable when different samples were taken from the same individuals over time. It was not possible to account for the variability between individuals by obvious differences in health, nutrition, or living habits. In addition, the trypanocidal titers did not vary significantly when stored for various lengths of time at -70 C. To examine the relationship between the titer of trypanocidal activity in a host and the degree of human serum resistance of the challenge trypanosome inoculum, mice (C57BL/6J) were pretreated with various amounts of different human serum and then infected with clones having different degrees of resistance to human serum. It was demonstrated that host susceptibility to an African trypanosome infection depends upon 2 variables: the level of trypanocidal activity in individual human serum and the degree of human serum resistance of individual clones of African trypanosomes. Based upon the animal model presented here, it is hypothesized that this relationship is under selective evolutionary pressure and will influence the susceptibility of animals in endemic areas as well as the transmission of human trypanosomiasis. PMID- 8459334 TI - In vitro growth of Babesia bovis in white-tailed deer (Odocoileus virginianus) erythrocytes. AB - Babesia bovis cultured in bovine erythrocytes was passaged into white-tailed deer (Odocoileus virginianus) erythrocytes and medium containing either white-tailed deer serum or bovine serum. Deer erythrocytes supported the growth of the parasite only in the presence of bovine serum. Cryopreserved cultures were recovered successfully in white-tailed deer erythrocytes. By light and electron microscopy, B. bovis structure appeared similar in host cells of either species. PMID- 8459335 TI - A comparison of mode of attachment and histopathogenicity of four tapeworm species representing two orders infecting the spiral intestine of the nurse shark, Ginglymostoma cirratum. AB - This study was undertaken to compare 2 species of Tetraphyllidea and 2 species of Trypanorhyncha with regard to the relationship between attachment structure morphology, mode of attachment, and tapeworm size, to damage at the sites of attachment in the Atlantic nurse shark, Ginglymostoma cirratum. Regions of the spiral intestine with worms attached were removed from 8 nurse sharks and sectioned according to conventional techniques. Sections of 5-50 specimens of each tapeworm species were examined. Regions of the spiral intestine devoid of worms were processed for characterization of the normal mucosa. The normal mucosa was found to consist of a folded surface covered with round-to-oval primary mucosal crypts. In the first 7 or 8 chambers of the spiral intestine the mucosal surface was thrown into secondary folds, forming ridges and secondary crypts. The primary mucosal crypts were lined with a single layer of columnar epithelium resting on a basement membrane. A highly cellular lamina propria and submucosa were found between the crypts and the muscularis mucosa. The small tetraphyllidean Pedibothrium brevispine was found with its scolex lying within the primary mucosal crypts with its hooks embedded in the basement membrane. Epithelial denudation was evident. The large tetraphyllidean Pedibothrium globicephalum was found with its bothridia engulfing large portions of the mucosa and its hooks embedded into the lamina propria. It was associated with moderate to severe mucosal necrosis. The small trypanorhynch Prochristianella tenuispine was found lying between the mucosal ridges in the secondary crypts with its tentacles either penetrating the epithelium, or occasionally, the lamina propria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8459336 TI - Morphological and physiological consequences of parasites encysted in the bulbus arteriosus of an estuarine fish, the sheepshead minnow, Cyprinodon variegatus. AB - The contribution of parasites to host population regulation is undefinable without knowledge of parasite effects on individual host performance and survival. Effects are best determined by examining performance of differentially parasitized hosts under the varying environmental conditions that characterize the host's habitat. The sheepshead minnow, Cyprinodon variegatus, an estuarine fish, is heavily parasitized in the bulbus arteriosus by the heterophyid trematode Ascocotyle pachycystis in semi-enclosed shallow bodies of water in northwestern Florida. Laboratory experiments were conducted to examine the morphological and physiological effects of parasitization of these fish. Differentially parasitized fish were compared for differences in ventricle weight and swimming performance. Parasitized fish ventricles were hypertrophied due to mechanical blockage of normal blood flow by metacercariae in the bulbus. Swimming performance generally was reduced by the presence of parasites, which had their most significant negative effect at cold temperatures and low dissolved oxygen levels. PMID- 8459337 TI - Different courses of granulomatous reactions around Schistosoma japonicum eggs in three strains of mice. AB - Tissue reaction around Schistosoma japonicum eggs was studied after implantation into 3 strains of mice. When freshly laid eggs were implanted into the livers of C57BL/6, CBA/J, and BALB/c mice, the tissue reaction, which could be divided into 3 stages, i.e., abscess formation, inflammatory stage, and fibrous stage, differed in persistence and reactivity according to the strain. This was true especially during the later 2 stages. In BALB/c mice, the inflammatory stage ended earlier. In CBA/J mice, it continued for the longest period and the subsequent fibrosis was the most marked. In C57BL/6 mice, the period of persistence of this inflammatory stage was intermediate, but these mice showed the highest degree of inflammatory reaction. When footpad reactions were tested, the delayed-type hypersensitivity reaction was generally comparable with the morphometric analysis. In presensitized mice implanted with lyophilized eggs, tissue reactivity was analogous to the fibrous stage of freshly laid egg implanted mice. In addition, there was an inverse relationship between antibody level and granuloma size, particularly at later reactions. The analysis of experimental granuloma formation presented in this report contributes to the study of stage-specific regulation. PMID- 8459339 TI - Evaluation of three methods for laboratory diagnosis of Strongyloides stercoralis infection. AB - The direct smear, a modified Baermann technique, and the agar plate culture method were compared for cost and efficiency in recovering Strongyloides stercoralis larvae in a hospital setting in Honduras. Of 427 stool samples, 9 were positive by the direct smear and 33 additional ones were detected by the Baermann technique; the agar plate culture method disclosed 28 more cases for a total of 70 S. stercoralis infections. The modified Baermann method was 3.6 times more efficient than the direct smear, and the agar plate culture increased the modified Baermann efficiency by 0.8 times. Cost for materials alone was cheapest for the direct smear; it increased 4 times for the modified Baermann method and 15 times for the agar plate culture method. This last technique required a better equipped laboratory, more time to perform, and the best trained, most skillful laboratory personnel. In field studies, prevalence of infection should determine the cost-effectiveness of the agar plate culture method; in a clinical setting, when S. stercoralis infection must be ruled out, the agar plate culture method should be made available to the medical community. PMID- 8459338 TI - A nonsubjective assay for antigenic modifications of the Babesia bovis parasitized erythrocyte surface. AB - Intracellular protozoan parasites induce numerous alterations in the invaded host cell, including antigenic modifications of the host cell plasma membrane. We have developed a quantifiable, non-subjective assay for the detection of novel antigenic reactivities on the host cell surface using as a model system bovine erythrocytes infected with Babesia bovis. Infected erythrocytes, metabolically labeled with L-[35S]methionine, were sensitized by incubation with bovine immune serum, then were captured in microtiter plates coated with rabbit anti-bovine IgG antibody. This technique enabled specific capture of B. bovis-infected cells with immune infection sera raised against B. bovis but not with similar sera raised against Babesia bigemina. This assay should be easily applicable to the study of other parasitic diseases. PMID- 8459340 TI - Effects of Schistosoma mansoni infection on phagocytosis and killing of Proteus vulgaris in Biomphalaria glabrata hemocytes. AB - With the use of a fluorescence microassay, in vitro phagocytosis and killing of Proteus vulgaris were measured in hemocytes of NIH albino Biomphalaria glabrata infected with Schistosoma mansoni for 1, 2, 3, or 4 wk. Although hemocytes of infected snails displayed decreased phagocytosis, relative to hemocytes of uninfected snails, at 4 wk postinfection (PI), they exhibited enhanced microbicidal activity at 3 wk PI. No microbicidal activity was detected in the plasma of either infected or uninfected snails. PMID- 8459341 TI - Parasitic arthropods of sympatric opossums, cotton rats, and cotton mice from Merritt Island, Florida. AB - Six species of parasitic arthropods were collected from 12 opossums (Didelphis virginiana), 8 species were obtained from 28 cotton rats (Sigmodon hispidus), and 4 species were collected from 10 cotton mice (Peromyscus gossypinus) from Merritt Island, Brevard County, Florida. The flea Polygenis gwyni was the only parasite that infested all 3 host species, and it was present in very high densities (mean intensity = 73.7) on the opossums. The American dog tick, Dermacentor variabilis, and the tropical rat mite, Ornithonyssus bacoti, both infested 2 host species but were principally associated with opossums and cotton rats, respectively. All remaining arthropod species were confined to single host species, suggesting host specificity by these parasites. The atopomelid mite Didelphilichus serrifer and the myobiid mite Radfordia sigmodontis constitute new state records for Florida. The reptile tick Amblyomma dissimile is recorded from a cotton mouse for the first time; Merritt Island may represent the most northerly location for viable populations of this tick in the U.S.A. PMID- 8459342 TI - Irradiation of Schistosoma mansoni cercariae impairs neuromuscular function in developing schistosomula. AB - Optimally attenuated larvae of Schistosoma mansoni (20 krad) are incapable of migrating farther than the lungs, and they induce high levels of resistance in mice to a subsequent challenge infection. The effect of gamma radiation on the parasite is described and related to the migratory pattern of attenuated larvae. Scanning electron microscopy revealed marked morphological differences between normal and irradiated larvae at the lung stage of development. The latter exhibited random constrictions, probably resulting from contraction of circular muscle fibers, at intervals along the length of the body and showed subtle differences in motility. We suggest these abnormalities account for persistence of attenuated larvae in the skin-draining lymph nodes and lungs, 2 events that are instrumental to the induction of protective immunity in this vaccine model. PMID- 8459343 TI - Ultrastructural determination of cystogenesis by various Toxoplasma gondii isolates in cell culture. AB - The tissue cyst stage of Toxoplasma gondii is important in relapsing disease seen in toxoplasmic encephalitis and retinochoroiditis. An in vitro culture system to examine the developmental biology of the tissue cyst stage would greatly aid in our understanding of this stage of the parasite's life cycle. We used transmission electron microscopy (TEM) and acid-pepsin digestion of infected cell cultures to determine the capability of 21 isolates of T. gondii to produce tissue cysts in cell cultures. All 21 of the isolates had acid-pepsin-resistant stages present, and tissue cysts could be demonstrated in 19 using TEM. The present study demonstrates that tissue cyst formation in vitro is a common phenomenon for T. gondii isolates. PMID- 8459344 TI - Perinatal infection with Trypanosoma vivax in a calf in Venezuela. AB - A case of perinatal infection by Trypanosoma vivax is reported in a 5-hr-old Carora local dairy breed calf. The levels of parasitemia were followed during 15 mo in the infected animal. Similarly, its immune response was monitored during 4 mo by the indirect fluorescent assay. Trypanosoma vivax was observed in Giemsa stained blood films collected during the first 4 mo of life from the infected calf. Positivity was detected on days 0, 35, 80, and 125 after first sampling. Antibodies against T. vivax were detected each time the indirect fluorescent assay was performed, showing low titers (1:80-1:160). The importance of a congenital route of transmission for this Trypanosoma species in cattle herds, on a continent where Glossina spp. flies are absent, is discussed. PMID- 8459345 TI - Cryptosporidium parvum infection after abrogation of natural killer cell activity in normal and severe combined immunodeficiency mice. AB - The role of natural killer (NK) cell activity in adult mice with severe combined immunodeficiency (scid mice) infected with Cryptosporidium parvum oocytes was evaluated. Adult BALB/c and scid mice were inoculated intragastrically with 10(6) C. parvum oocysts after the administration of anti-asialo-GM1 or control normal rabbit serum. Groups of animals were evaluated for splenic NK cell activity and examined histopathologically at 2, 4, and 6 wk postinfection. Virtual elimination of splenic NK cell activity by anti-asialo-GM1 treatment was demonstrated. Nonetheless, no differences in the occurrence of illness, death, or histopathologic evidence of infection were observed between anti-asialo-GM1 treated and control-treated BALB/c or scid mice. We conclude that NK cell activity, at least as measured in the spleen, does not play a significant role in murine host defense of cryptosporidial infection, even in the absence of functional B and T cells. PMID- 8459346 TI - Cytopathological changes induced by Haemogregarina myoxocephali in its fish host and leech vector. AB - The cytopathological effects of infection with Haemogregarina myoxocephali were investigated by light and electron microscopy in its fish host, Myoxocephalus octodecemspinosus, and in its leech vector, Malmiana scorpii. Gamont-infected erythrocytes in fish appeared vacuolated and exhibited shrinkage and altered shape consistent with loss of cytoskeletal integrity. Infected intestinal epithelial cells in leeches showed changes suggestive of recruitment of host metabolic functions by the developing parasite, including hypertrophied mitochondria and accumulations of endoplasmic reticulum and secretory vesicles next to the parasitophorous vacuole. PMID- 8459347 TI - Echinococcus multilocularis identified in Indiana, Ohio, and east-central Illinois. AB - Echinococcus multilocularis was identified in a coyote in Indiana in January 1990. Subsequently, 300 wild canids (red foxes, gray foxes, coyotes) were collected from Indiana, Ohio, Illinois, Michigan, and Kentucky and examined for this parasite. Of these, 41 (13.7%) were infected with E. multilocularis. Infected animals were from northern and central Indiana, northwestern Ohio, and east-central Illinois. Twenty-nine of 162 (17.9%) animals from northern and central Indiana were positive, versus 0 of 83 from southern Indiana. Infected animals from northern and central Indiana included 16 of 71 (22.5%) red foxes and 13 of 70 (18.6%) coyotes. In Ohio, 6 of 22 (27.3%) red foxes were infected, and in Illinois, 6 of 17 (35.3%) coyotes were positive. Mean intensity of infection for red foxes was 372 worms (range, 2-3, 640), and for coyotes, 6,579 worms (range, 1-52,000). These findings constitute new state and distribution records for E. multilocularis and a significant range extension for this parasite species in central North America. PMID- 8459348 TI - Long-lasting parasitism of Strongyloides venezuelensis in Mongolian gerbils (Meriones unguiculatus). AB - Mongolian gerbils (Meriones unguiculatus) were infected with 100, 1,000 and 10,000 Strongyloides venezuelensis infective larvae (L3) to determine the duration of fecal egg output. Eggs per gram of feces (EPG) were counted chronologically, and adult worms in the small intestine were recovered on 100 days after infection. Changes of EPG in Mongolian gerbils infected with 10,000 L3 also were observed for 450 days. EPG was stable for each dose after the peak value noted 9 or 10 days after the infection. The EPG and number of worms recovered were dependent on the dose. The high EPG value continued for 450 days. These results demonstrate that Mongolian gerbils allowed a long-lasting parasitism of S. venezuelensis. Strongyloides venezuelensis-Mongolian gerbil systems may be useful for parasitological study of S. venezuelensis. PMID- 8459350 TI - Prayer: beyond the ordinary. PMID- 8459349 TI - Confidentially speaking. PMID- 8459351 TI - A mother asks, where is your compassion? PMID- 8459352 TI - Soul therapy: humor & music with African-American clients. PMID- 8459353 TI - Music: arousing the human spirit. PMID- 8459354 TI - Spiritual care of homeless men--what helps? What hinders? PMID- 8459356 TI - Being the best nursing leader you can be. PMID- 8459355 TI - Professional organizations: setting nursing's agenda. Interview by Judy Shelly. PMID- 8459357 TI - A primary prevention group for latency age children dealing with adoption issues. AB - The authors describe an eight-session primary prevention group program for latency age children who were dealing with adoption issues. The structure and the process of the group are described and the effectiveness of the program is evaluated. One of the authors, who is both an adoptive parent and a nurse psychotherapist, was the group leader. The group served to facilitate the lifelong process of dealing with adoption issues. PMID- 8459358 TI - Homeless children: interdisciplinary drug prevention intervention. AB - Homelessness among children has been called a national tragedy. Homeless children, by virtue of their unique situation, are particularly vulnerable for early initiation of and sustained participation in substance abuse behaviors. The authors describe homeless children in relation to drug abuse etiology research, discuss current prevention strategies, suggest necessary components of an interdisciplinary prevention curriculum for homeless preschool children, and delineate methods for delivering the curriculum to the children. Nurses, given their unique role in the healthcare delivery system as well as a holistic world view, are in an unparalleled position to facilitate the design and implementation of such curricula. PMID- 8459359 TI - We can do this! PMID- 8459360 TI - Advocating for seriously emotionally disturbed children and their families: an overview. PMID- 8459361 TI - An interview with Ann Burgess, DNSc, RN, CS, FAAN. Interview by Patricia C Pothier. PMID- 8459362 TI - What are those antennae, anyway? PMID- 8459363 TI - Support systems and caretaking behaviors of adolescent and older mothers: the first year after delivery. AB - This study investigated differences in support systems and caretaking behaviors of adolescent and older mothers. Nineteen adolescent and 25 older, Caucasian, first-time mothers completed the Community Interaction Checklist and Home Observation for Measurement of the Environment one, six, and 12 months after delivery. No significant differences in number or quality of daily interactions existed, although teens interacted more with helping agents and less with the baby's father and work contacts. No significant relationship between support and caretaking occurred. Teens may not be the isolated group sometimes depicted in the literature. They are a diverse population whose varying, individual needs must be considered prior to intervention. PMID- 8459364 TI - Hepatocyte ultrastructure following exposure to aroclors and pure polychlorinated biphenyls. AB - Three agriculturally important minor species, the goat, rabbit, and duck, were exposed to various subclinical levels of pure polychlorinated biphenyls (PCBs) and/or PCB mixtures (Aroclors) for short periods of time. Upon sacrifice, liver samples were prepared for ultrastructural observation. Regardless of species, hepatocytes displayed qualitatively similar morphological responses to PCB exposure. At lower exposure levels, cellular changes included increased density of mitochondrial matrix and proliferation of endoplasmic reticulum. At higher exposure levels, degradative changes such as cytoplasmic loss and peripheralization of cytoplasm and organelles became more obvious. When compared quantitatively, it was obvious that goats were much more sensitive to PCB exposure than either rabbits or ducks. Goats showed extensive hepatocyte degradation (cytoplasmic and nucleoplasmic leaching) at exposures of 2 mg/kg body weight of Aroclor 1254. Such species-related differences in response to chlorinated biphenyls cautions against the use of single species animal models in xenobiotic exposure studies. PMID- 8459365 TI - Selective retention of polychlorinated biphenyl congeners in lung and liver after single-dose exposure of infant mice to Aroclor 1254. AB - Infant male Swiss mice (8 days old) were given a single i.p. injection of 500 mg/kg of the polychlorinated biphenyl (PCB) mixture, Aroclor 1254, a treatment found in previous studies to result in promotion of nitrosamine-initiated lung and liver tumors. The amounts of the nine congeners that account for > 90% of the PCBs still present 1 day after treatment were quantified in liver, lung, and remainder of carcass 1, 7, 56, 84, and 112 days after treatment. Rates of decrease (half-times, dt1/2s) for total PCB concentration and for individual congeners were compared within and between compartments and with body weight doubling time. In carcass (adipose compartment) there was net loss beyond that expected from dilution due to growth, with the predicted lower dt1/2s for the more metabolizable congeners. By contrast, in lung, after a rapid loss during the 1st week, all congeners except for #153 (2,2'4,4'5,5'-hexachlorobiphenyl [HCB]) were retained and decreased in amount only as a function of dilution due to growth. One result was that congeners #105 (2,3,3',4,4'-pentachlorobiphenyl [PeCB]) and #138 (2,2',3,4,4',5'-HCB) constituted a higher proportion in lung than in carcass. A complex pattern was observed in liver: relative to carcass, there was retention of all congeners during the prepubertal growth phase, again with specific enrichment of #105, followed by more rapid depletion of certain congeners later. PCB-binding proteins and changes in lipid composition may contribute to these phenomena, which are of human relevance in that these congeners are commonly found in human serum and adipose samples. PMID- 8459366 TI - Hepatic and renal ultrastructural changes in cockerels exposed to cadmium chloride and subsequent interaction with organophosphate insecticide. AB - Ultrastructural alterations of the liver and kidneys of cockerels exposed to 100 ppm of cadmium chloride (CdCl2) and subsequent interaction with an organophosphorus compound (methylobromofenvinphos) were studied. Four groups, each consisting of 25 birds, included 100 ppm of CdCl2 in drinking water for 4 weeks (Group A), 100 ppm of CdCl2 for 4 weeks followed by a single dose of 240 mg/kg of methylobromofenvinphos (IPO 63 compound) (Group B), single dose of 240 mg/kg of IPO 63 compound (Group C), and untreated control (Group D). Three birds from each group were sacrificed 24 hr post treatment with IPO 63 compound and tissue pieces were collected for electron microscopic study. Ultrastructural changes in hepatocytes included swollen mitochondria with cavitation, dilated rough endoplasmic reticulum, numerous lysosomal bodies, myelin figures, depletion of glycogen granules, and numerous vacuoles containing degenerated membranes in birds that interacted with CdCl2. In a few cells the nuclei were markedly damaged with dilation of envelope. Renal corpuscles of CdCl2 showed irregular foot processes and thickening of the glomerular basement membrane. The proximal tubular cells of CdCl2 birds showed marked ultrastructural alterations, including numerous lysosomal bodies, few fat droplets, membrane bound vacuoles studded with polyribosomes, swollen mitochondria with fragmented cristae surrounded by rough endoplasmic reticulum, vacuoles containing myelin figures, and damaged nuclei with dilated envelope. Minor ultrastructural alterations were observed in the liver and kidneys of birds treated with cadmium alone and of those treated only with IPO 63 compound. These observations suggest that treatment with CdCl2 and then subsequent interaction with IPO 63 compound causes hepatic and renal damage that appears to be additive. PMID- 8459367 TI - Reaction of pulmonary macrophages exposed to nickel and cadmium in vitro. AB - We examined the morphological and functional characteristics of goat alveolar macrophages exposed in a serum-free medium in vitro for up to 20 hr to cadmium as CdCl2 and nickel as NiCl2. The concentration of these metals varied from 0.04 to 1.00 mM. Cadmium reduced the viability and phagocytosis of macrophages and increased the release of lactate dehydrogenase from cells into the culture medium at all the concentrations tested. Alterations in macrophage surface morphology, evaluated by scanning electron microscopy, consisted of withdrawal of pseudopodia and rounding of cells exposed to 0.20 and 1.00 mM of CdCl2. In nickel-exposed macrophages these changes were marked only at higher concentrations of the metal. Higher concentrations of Ni were necessary to produce effects similar to those produced by lower Cd concentrations. Our results demonstrated that the higher toxicity of cadmium as compared to that of nickel for alveolar macrophages is related to a difference in the alterations in the morphology and function of the exposed cells. PMID- 8459368 TI - Environmental risk factors of cancer and their primary prevention. AB - The evaluation of the influence of different environmental carcinogenic factors requires interdisciplinary cooperation. Related studies include epidemiological surveys and air, water and soil, chemical, toxicological, and microbiological analyses, supplemented by experimental verification of suspected ecological pathogens and cofactors. A balance of carcinogens and protective agents in the external environment and in the human body is recommended for an ecologically oriented prevention. Toxicological control of the food chain using modern technology (Proton-induced X-ray emission (PIXE), nuclear activation analysis, and induced coupled plasma) should be integrated with microanalyses at the cellular level (by X-ray scanning electron microscopy, nuclear magnetic response, PIXE, and spontaneous and delayed chemiluminescence for balance of free-radicals and their scavengers). A pilot cross-disciplinary study conducted in the area of a "cluster" of human neoplasms and cattle leukemia, in comparison with control villages in Poland, showed an excess in Pb, Hg, Ni, Rb, K, Mn, Cr, and Zn, accompanied by a nutritional deficiency in Mg, Ca, Fe, Co, and Se in the food chain of the "cluster." The living and breeding houses in this area were significantly more contaminated with the toxicogenic molds Aspergillus flavus and Penicillium meleagrinum and by nitrate and nitrite in the drinking water. Our experiments showed that selenium deficiency stimulated the growth of fungi and some bacteria and increased the immunosuppressive and teratogenic effects of aflatoxin B1. New methods of protection of the indoor environment against microbiological contamination and laser-related biotechnology for nutritional prevention of selenium deficiency and associated risk of neoplasms have been introduced. Primary prevention requires a large scale application of highly sensitive methods for early detection of risk factors in the environment, food, water, and at the personal level, as well as education of the society and an integrated common corrective action. PMID- 8459369 TI - The doctor's aim in a pluralistic society: a response to 'healing and medicine'. PMID- 8459370 TI - Serendipity and spice: the place of quotation in medical writing. PMID- 8459371 TI - The portrayal of the physician in non-medical literature-sexual fantasies and encounters. PMID- 8459372 TI - Rheumatism and the thyroid. PMID- 8459373 TI - Investigation and management of loss of efficacy of an antiepileptic medication using carbamazepine as an example. AB - Cases reported as loss of efficacy (secondary failure) of carbamazepine (CBZ) for epilepsy were analysed to determine the cause. In these cases, seizures previously controlled with CBZ, recurred or increased in frequency. The following causes were identified in 131 cases where adequate information was available: use for types of epilepsy where this drug is not recommended, lowering of the blood levels of the drug on switching over from branded to a generic CBZ, change in the galenic form, drug interactions, progression of the underlying brain pathology such as a brain tumor, and unexplained increase in the blood levels of the drug. In cases where the increase in seizures was transient no special measures or changes in therapy were required. Unexplained failure occurred only in seven cases (5.3%). Based on this information, a flow chart was designed to evaluate such a problem step by step and to take appropriate measures. Only when true therapeutic failure is identified, should another antiepileptic drug be substituted for CBZ. Similar approach can be used for other antiepileptic drugs. PMID- 8459374 TI - Postoperative nausea and vomiting: a comparison of anti-emetic drugs used alone or in combination. AB - Drugs with anti-emetic properties can exert their actions at more than one receptor site, histamine H1, muscarinic cholinergic or dopaminergic D2 receptors. This study was designed to test the hypothesis that a combination of drugs acting at different receptor sites in lower than standard doses would be at least as effective as a standard therapeutic dose of a single anti-emetic agent. A combination of droperidol, hyoscine and metoclopramide in subtherapeutic doses has been shown to be at least as effective as droperidol (1.25 mg) alone. In both groups there was a low incidence of emetic sequelae in the first 3 hours postoperatively. PMID- 8459375 TI - Cigarette smoking increases white blood cell aggregation in whole blood. AB - We studied the effect of chronic cigarette smoking on white blood cell aggregation, increased aggregation predisposes to microvascular occlusion and damage. Current smokers had significantly increased white blood cell aggregation when compared with non smokers. The presence of chronically activated white blood cells in current smokers may be relevant in the pathogenesis of ischaemic vascular disease. PMID- 8459376 TI - The adequacy of cervical spine radiographs in the accident and emergency department. AB - One hundred and twenty radiographs of the cervical spine were performed at the request of the Accident and Emergency (A & E) department over a 6 week period. These consecutive films were reviewed for adequacy of anatomical demonstration of the complete cervical spine. The initial series of three films presented to the A& E staff achieved this objective in only 55% of cases overall, although further radiographic examinations requested before the patient left the department raised this figure to 75% for the lateral view and to 70% for the combined anteroposterior (AP) views. From the data it can be predicted that if every patient whose first 3 films were inadequate had received further investigation, the cervical spine would have been well visualized on approximately 90% of radiographs in each plane. The availability of radiologists for advice and their involvement with senior A & E staff in teaching are important factors in improving this situation. PMID- 8459377 TI - Effect of anoreceptive intercourse on anorectal function. AB - This study is the first published assessment of the effect of anoreceptive intercourse (ARI) on anal sphincter tone and function. Forty anoreceptive (AR) male homosexuals were compared with 18 age matched non-anoreceptive (non-AR) heterosexual males. Subjects were questioned about ARI, defaecation and faecal incontinence. Anal resting pressure, maximum voluntary squeeze pressure, anal mucosal electrosensitivity, perineal descent and rectal sensation were measured in all subjects. Fourteen of the AR subjects but only one of the non-AR subjects had symptoms of frequent anal incontinence (P < 0.05). There was a significant reduction in both maximum anal resting pressure (P < 0.01) and anal mucosal electrosensitivity (P < 0.05) and a significant difference in the anal resting pressure profile (P = 0.02) in the AR subjects compared with the non-AR subjects. There was a significant reduction in maximum squeeze pressure in AR subjects with anal incontinence compared with either AR subjects without anal incontinence (P < 0.01) or non-AR subjects (P < 0.01). There were no significant differences in stoll consistency, frequency of defaecation, perineal descent or rectal sensation between the groups. ARI is associated with reduced resting pressure in the anal canal and an increased risk of anal incontinence. The risk of incontinence is greatest amongst AR subjects with reduced maximum squeeze pressure. PMID- 8459378 TI - The value of screening for diabetes in patients with skin sepsis. AB - Four hundred and eighty-two patients with spontaneous skin and superficial sepsis and 291 controls of similar age and sex underwent random capillary blood glucose measurements in order to assess whether screening for diabetes in patients presenting with skin sepsis to an Accident & Emergency Department detects a greater number of cases than that present in the background population. All subjects with a concentration > 7.8 mmol/l were subsequently followed up with a 75 g oral glucose tolerance test. Forty-two (8.7%) of the 482 skin sepsis patients had a capillary blood glucose > 7.8 mmol/l compared to eight (2.7%) of the 291 without sepsis (chi 2 = 9.71, P < 0.002). Of these, 26 of the skin sepsis group and 7 of the control group attended for follow up. Of those who attended, 13 of the skin sepsis group had an abnormal glucose tolerance test (seven diabetes, six impaired glucose tolerance-IGT) compared to two (one diabetes, one IGT) of the control group (chi 2 = 2.87, P < 0.1). The difference in cases of frank diabetes between the two groups was not statistically significant. Of the total eight diabetic cases identified, five (on direct questioning) had symptoms of hyperglycaemia (thirst, polyuria and/or weight loss) and two of the others were obese, one of whom had documented ischaemic heart disease. Thus, while most cases of diabetes in patients with skin sepsis could be detected by specifically asking about hyperglycaemic symptoms and performing a blood glucose estimation when these are present, we suggest that the screening of patients with skin sepsis over 40 years of age provides an opportunistic method of screening. This strategy should yield clinically significant numbers of abnormal cases. PMID- 8459379 TI - The changing pattern of imported malaria in British visitors to Kenya 1987-1990. AB - Following a sudden increase of imported malaria from Kenya in December 1989 January 1990, an investigation was set up to identify risk factors for travellers' malaria. A questionnaire asking for details of travel patterns and compliance with prophylaxis was sent to cases reported over the 6-month Kenyan winter period. Quarterly malaria attack rates between January 1987 and June 1991 were calculated and linked to meteorological conditions in Mombasa. The number of travellers to Kenya has doubled in the 4 years studied and the quarterly rates varied 4-fold over this period. There was no clear seasonal pattern of malaria in travellers, nor was there any clear relation of malaria to coastal rainfall. Compliance with chemoprophylaxis was poor, with only 16% of cases using currently advised regimens. While the annual malaria attack rate per 10,000 travellers decreased by 37% over the study period, the total numbers of malaria cases imported from Kenya rose by 61%, reflecting the increase in the numbers of travellers to the region. As the popularity of East Africa as a tourist destination continues to increase, Kenya will remain an important and significant source of malaria imported into the UK. PMID- 8459380 TI - Personal immunization against hepatitis B. AB - Doctors represent a high risk category for contracting hepatitis B virus. We report obstacles to our vaccination programme. Thirty per cent of the doctors (mainly Middle Eastern origin) were naturally immune to hepatitis, 29% received vaccination on completion of their pre-employment medical. However, 32% did not present for vaccination despite a total of 224 letters being dispatched, an average of 5.5 letters per doctor. Three medical staff were found to be HbsAg positive. More encouragement is required for those doctors who fail to attend for immunization. Measures such as: being a pre-requisite for employment, or withholding pay could be considered in high risk areas. PMID- 8459381 TI - Management of service personnel with a history of penicillin allergy: discussion paper. AB - A false label of penicillin allergy may have important consequences for wartime medical evacuation. This article outlines the antibiotic protocol for war wounds, the current status of tests to diagnose true penicillin allergy and suggests a strategy for the management of personnel with a history of such allergy. PMID- 8459382 TI - Beethoven's nephropathy and death: discussion paper. AB - The autopsy description of Beethoven's nephropathy is so typical of renal papillary necrosis, that the diagnosis is as near to certain as is possible, in the absence of a histological examination. A review of the symptoms and clinical course of Beethoven's final illness is consistent with this diagnosis. It is proposed that the cause was an acute onset diabetes mellitus, complicating chronic pancreatitis. Beethoven's case appears to be the first report in the literature of an autopsy proven case of renal papillary necrosis. PMID- 8459383 TI - The Rev Dr J I Bleasdale and the Medical Society of Victoria. PMID- 8459384 TI - A computer-aided analysis of John Locke's medical vocabulary. PMID- 8459385 TI - Use of the radial forearm in intraoral reconstruction. PMID- 8459386 TI - Polyneuritis cranialis and C-ANCA: is it limited Wegener's granulomatosis? PMID- 8459387 TI - Foregut duplication cysts: a diagnostic challenge. PMID- 8459388 TI - Erosive arthritis in a patient with mycosis fungoides. PMID- 8459389 TI - Linear sebaceous naevus syndrome with oncogenic rickets and diffuse pulmonary angiomatosis. PMID- 8459390 TI - A Kurdish fracas. PMID- 8459391 TI - Chronic nutmeg psychosis. PMID- 8459392 TI - Diet and coronary heart disease. PMID- 8459393 TI - Diet and coronary heart disease. PMID- 8459394 TI - Modulation of leukocyte genetic expression by novel purine nucleoside analogues. A new approach to antitumor and antiviral agents. PMID- 8459395 TI - Synthesis and pharmacological evaluation of hexahydrofluorenamines as noncompetitive antagonists at the N-methyl-D-aspartate receptor. AB - The noncompetitive (PCP) site of the N-methyl-D-aspartate (NMDA) receptor complex has been implicated in a number of pathologies, including the etiology of ischemic stroke. Recent testing has shown that cis-1,2,3,4,9,9a-hexahydro-N methyl-4aH-fluoren-4a-amine (1), a rigid analog of PCP, is a potent antagonist at this site (IC50 = 30 nM for displacement of [3H]TCP). On the basis of this finding, a number of derivatives encompassing variations in stereochemistry, amine substitution and position, aromatic and aliphatic ring substitution, and heteroatom ring substitution have been prepared to explore the structure-activity relationships around this ring system. All compounds were evaluated for their PCP receptor affinity; potent compounds were also tested in vitro (cultured neurons) and in vivo (prevention of NMDA-induced lethality in mice). The present hexahydrofluorenamines demonstrated a wide range of potencies, with optimal affinity concentrated in analogs containing a heteroatom (sulfur) in the B ring (IC50 of 11 nM versus [3H]TCP for 16b), methyl substitution on the amine, and R stereochemistry at the 4a position. No significant improvement in affinity was seen with aromatic ring substitution. Aliphatic ring substitution, large amine substituents, and alterations in the position of amine substitution on the ring system resulted in a loss of potency. To explore the effect of simultaneous hydrogen bonding with a putative receptor atom from two directions, the 2 hydroxymethyl derivatives were prepared. This substitution resulted in a loss in receptor binding affinity. Molecular modeling, X-ray, and NMR studies have been used to determine an optimal conformation of the hexahydrofluoreneamines at the receptor site. PMID- 8459396 TI - Centrally acting serotonergic agents. Synthesis and structure-activity relationships of C-1- or C-3-substituted derivatives of 8-hydroxy-2-(di-n propylamino)tetralin. AB - The synthesis and structure-activity relationships (SAR) of C-1- or C-3 substituted derivatives of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) are described. These analogs were synthesized via alkylation of the tetralone derivatives followed by reductive amination. All of the analogs were inactive at the dopamine D2 receptor. Among the 8-OMe or 8-OH C-1,N-disubstituted analogs synthesized, the cis analogs were more potent in the 5-HT1A binding assay than the corresponding trans analogs. However, in the case of 1-(cyclopropylmethyl)-N n-propyl analogs, the trans isomer has a slightly higher 5-HT1A affinity than its cis counterpart. The order of binding potency for C-1 substitution was found to be allyl > hydroxymethyl > n-propyl > cyclopropylmethyl >> carbomethoxy. Interestingly, the 5-OMe analogs were found to be inactive in both the 5-HT1A and dopamine D2 binding assays. In the C-3 allyl-substituted analogs, 5-HT1A agonist activity was found to be considerably lower. In these examples, the trans analogs showed weak 5-HT1A binding activity whereas the cis analogs were inactive. Analogs with C-1,N,N-trisubstitution also showed a marked decrease in 5-HT1A binding affinity. Overall, the SAR study showed that cis C-1 substitution maintains the 5-HT1A agonist activity of 8-OH-DPAT whereas trans C-1 substitution displays somewhat diminished activity. On the other hand, the trans C-3 substitution shows modest agonist activity whereas cis C-3 substitution removes the activity completely. PMID- 8459397 TI - Substituted benzamides with conformationally restricted side chains. 5. Azabicyclo[x.y.z] derivatives as 5-HT4 receptor agonists and gastric motility stimulants. AB - The syntheses of benzamides containing azabicyclo[x.y.z] side chains and their 5 HT4 receptor agonist and 5-HT3 receptor antagonist properties are described. These compounds were designed to mimic higher energy conformations of quinolizidine and indolizidine. High potency was achieved for both activities although an exactly paralleling SAR was not apparent. Introduction of O and S resulted in only marginal differences in potency which was more apparent for 5 HT3 antagonism. The introduction of a methyl group alpha to the basic nitrogen resulted in a reduction in 5-HT4 receptor agonist potency. Renzapride (5f) was identified for further evaluation for which both enantiomers had an identical pharmacological profile, as did an azatricyclic 9b, which contained a combination of the steric bulk of the two separate enantiomers. PMID- 8459398 TI - 1,2-Cyclomethylenecarboxylic monoamide hydroxamic derivatives. A novel class of non-amino acid angiotensin converting enzyme inhibitors. AB - A series of monoamidic derivatives of cis- and trans-1,2-cyclohexanedicarboxylic and 1,2-cyclopentanedicarboxylic acids bearing either a carboxylic, sulfhydrylic, or hydroxamic group in the side chain were synthesized and evaluated in vitro for their inhibitory activity against angiotensin converting enzyme. The compounds were designed as potential ACE inhibitors of novel structure, assuming that a monoamidic residue of an 1,2-cyclomethylenedicarboxylic acid could be an alternative structure to the acylproline moiety, the carboxyl-terminal portion common to various ACE inhibitors. The most active compounds were found in the hydroxamic derivatives of cyclohexane series; within this series of derivatives a marked increase of potency was caused by alkylation of the amidic nitrogen with a methyl or ethyl group. Therefore enantiomers of the selected hydroxamic derivatives of cis- and trans-1,2-cyclohexanedicarboxylic acid were prepared by two different chiral synthetic routes and evaluated in vitro for their ACE inhibitor potencies. The active enantiomers both of the cis series (21a, 21c) and trans series (16b, 16d) were found to have all R configuration at the C-2 and R or S configuration at the C-1, while in the classical ACE inhibitors S configuration at the terminal carboxylate (corresponding to the C-1 of our compounds) is strictly required for activity. The most potent compound of the series was (1S,2R)-cis-2[[[2-(hydroxyamino)-2-oxoethyl]methylamino]carbonyl] cyclohexanecarboxylic acid (21a) with an IC50 value of 7.0 nM compared with the value of 3.0 nM for captopril. Further 21a was shown to be highly selective and competitive ACE inhibitor. These results indicate that this non-amino acid structure of inhibitors meets the ACE active site requirements for the binding. The binding compatibility of the most active compounds with a model of ACE active site was evaluated by molecular modeling techniques. PMID- 8459399 TI - Epoxysuccinyl dipeptides as selective inhibitors of cathepsin B. AB - Epoxysuccinyl dipeptide analogs of E-64 (R-EpsLeuPro-R') (Figure 1) have been synthesized with the carboxylate group on the epoxide ring either free (R = OH) or converted to an ester or an amide (R = EtO or i-BuNH) and with the C-terminal amino acid proline either blocked (R' = OBzl) or free (R' = OH). These compounds were used to investigate the recently reported selectivity of this type of inhibitor for the lysosomal cysteine protease cathepsin B. It was shown that derivatization of the carboxylate on the epoxide ring confers selectivity for cathepsin B over papain only when it is combined to a dipeptidyl moiety with a free negatively charged C-terminal residue. It is proposed that this selectivity reflects interactions with histidine residues on a loop located in the primed subsites of cathepsin B which provides a positively charged anchor for the C terminal carboxylate group of the inhibitor. The primed subsite loop of cathepsin B is not found in other cysteine proteases of the papain family and offers a unique template for designing selectivity in cysteine protease inhibitors. PMID- 8459400 TI - Design of thymidylate synthase inhibitors using protein crystal structures: the synthesis and biological evaluation of a novel class of 5-substituted quinazolinones. AB - The design, synthesis, and biological evaluation of a new class of inhibitors of thymidylate synthase (TS) is described. The molecular design was carried out by a repetitive crystallographic analysis of protein-ligand structures. At the onset of this project, we focused on the folate cofactor binding site of a high resolution ternary crystal complex of Escherichia coli TS, 5' fluorodeoxyuridylate (5-FdUMP) and a classical glutamate-containing folic acid analog. A preliminary ternary crystal structure of a novel compound was successfully solved. Upon analysis of this initial complex, further structural elaborations were made, and a series of active 5-(arylthio)quinazolinones was developed. The synthetic strategy was based on the displacement of a halogen at the 5-position of a quinazolinone by various aryl thioanions. The compounds were tested for inhibition of purified E. coli and/or human TS, and were assayed for cytotoxicity against three tumor cell lines in vitro. Significant thymidine protection effects were observed with several of the inhibitors, indicating that TS was the intracellular locus of activity. PMID- 8459401 TI - Systematic substitution of an oxytocin antagonist with D-amino acids: unexpected high antagonistic potency of the D-Cys6-substituted analogue. AB - We report twelve analogues (1-12) of [Pmp1,D-Trp2,Arg8]oxytocin, PA (parent antagonist), (Pmp = beta,beta-pentamenthylene-beta-mercaptopropionic acid), which is a potent antagonist (pA2 = 7.77) of the uterotonic effect of oxytocin (OT) in rats. The analogues were designed by replacement of each optically active amino acid residue at positions 3-8 in PA with a D-amino acid. Analogues 1-8, featuring D-amino acids in the ring portion, were weaker antagonists than PA or were inactive. Unexpectedly, replacement with D-Cys6 gave analogue 9, pA2 = 8.29, which is more than 3 times as potent as PA, and replacement with D-Pen6 gave analogue 10, pA2 = 7.98, also more potent than PA. Replacement with D-Pro7 and D Arg8 gave analogues 11 and 12, which are approximately equipotent or somewhat more potent than PA. These data suggest that neither the orientation of the tail sequence with respect to the plane of the ring portion of an antagonist nor the configuration of individual amino acids in the tail sequence may be critical for preservation of antagonism to the uterotonic action of OT. In the antidiuretic assay, analogues 9 and 12 were very weak partial agonists and had estimated pA2 = < 6.3 and < 5.6, respectively. Analogue 9 constitutes an interesting lead for the future design of OT antagonists with different molecular requirements than those featuring L-Cys6 as a substituent. PMID- 8459402 TI - Synthesis and tubulin binding of novel C-10 analogues of colchicine. AB - A series of novel C-10 derivatives of colchicine have been prepared and evaluated for inhibition of in vitro microtubule assembly and of [3H]colchicine binding to tubulin. The C-10 substituent of colchicine was replaced by halogens, alkyl and alkoxy groups, and hydrogen. Many of these compounds are available by nucleophilic substitution of 10-fluoro-10-demethoxycolchicine (9) without concomitant formation of ring contraction products. Compound 9 is prepared by reaction of (diethylamino)sulfur trifluoride with colchiceine. Unlike most reactions of colchiceine, the colchicine rather than the isocolchicine regiosiomer is the predominant product of this reaction. It was found that modification of the C-10 substituent of colchicine had a relatively minor effect on the potency of the colchicinoids. The electronic nature of the substituent had no significant effect on the efficacy of the compound, indicating that hydrogen bonding or polar interactions between the C-10 substituent of colchicinoids and an amino acid in the colchicine binding site on tubulin are not present in the colchicine-tubulin complex. A decrease in activity was observed with increasing length of the alkyl chain bonded to the C-10 position, but potency was less affected when the alkyl groups were positioned in close proximity to the C-10 carbon of the tropone ring. It is concluded that the steric rather than the electronic properties of the C-10 substituent are the predominant determinants of activity in this series. PMID- 8459403 TI - 2-substituted 1,2-dihydro-3H-dibenz[de,h]isoquinoline-1,3-diones. A new class of antitumor agent. AB - A new class of antitumor agents, having structural analogy to amonafide, but differing by the addition of a fourth ring in the nucleus, was synthesized conveniently from anthracene. Compounds with a variety of substituents, containing a basic nitrogen atom and located on the imide nitrogen, were prepared. Thirteen of 19 new compounds had greater growth inhibitory potency than amonafide in a panel of cultured murine and human tumor cells using the sulforhodamine B and MTT dye assays. The most active agents were similarly more toxic than amonafide to normal neonatal rat myocytes in vitro, but they had better chemotherapeutic indexes. From these compounds, the one with a 2 (dimethylamino)ethyl side chain (named azonafide) was chosen for further study. It showed high potency against a panel of cultured human colon cancer cells and it was active against ip P388 leukemia and subcutaneous B16 melanoma in mice. Preliminary structure-activity correlations suggest that the basicity of the side chain nitrogen and the length of side chain are important determinants of antitumor potency in vitro. Steric hindrance and rigidity of the side chains might be other determinants. PMID- 8459404 TI - Orally active beta-lactam inhibitors of human leukocyte elastase. 2. Effect of C 4 substitution. AB - The effect of changing the C-4 substituent of 3,3-diethyl-1 [(benzylamino)carbonyl]-2-azetidinone on inhibition of HLE and in a model of HLE induced lung damage in hamsters was explored. Substituents at this position do not appear to interact strongly with HLE with the most potent compounds having k(obs)/[I] = 6900 M-1 s-1. However, substituents at this position had a marked effect on in vivo activity. The greatest oral activity in the lung hemorrhage assay was achieved with C-4 aryl carboxylic acid ethers (60-85% inhibition at 30 mg/kg po). Based upon the established mechanism of inhibition by these compounds, the C-4 substituent would be released, and therefore, the pharmacological potential of these C-4 substituents was of considerable concern. Fortunately, compounds containing 4-hydroxybenzoic acid and 4-hydroxyphenylacetic acid ethers at C-4 were among the most active analogs. These phenolic acids are also found as urinary metabolites in healthy humans. Other heteroaryls at C-4 were also orally active in this model despite relatively modest enzyme activity. PMID- 8459405 TI - Neuraminidase-resistant hemagglutination inhibitors: acrylamide copolymers containing a C-glycoside of N-acetylneuraminic acid. AB - Copolymers consisting of a polyacrylamide backbone with side chains terminated in C-glycosidic analogs of N-acetylneuraminic acid were synthesized by free radical copolymerization of alpha-2-C-[3-[[2-(N-acryloylamino)ethyl]thio]propyl]-N- acetylneuraminic acid (5) with acrylamide. Unlike natural and synthetic polyvalent materials that contain N-acetylneuraminic acid in O-glycosidic form, these C-glycosidic copolymers resist neuraminidase-catalyzed cleavage of the neuraminic acid residue from the copolymer backbone. Examination of these C glycosidic copolymers in a hemagglutination inhibition assay indicated that they are as effective in vitro as polyvalent O-glycosidic copolymers in inhibiting agglutination of erythrocytes by influenza virus. The minimum value of the inhibition constant, calculated on the basis of the concentration of Neu5Ac groups in solution, is Ki(HAI) approximately 10(-7) M for both copolymers. The inhibitory potency of the C-glycoside-based copolymers becomes more significant at lower concentrations of Neu5Ac moieties in solution than does the inhibitory potency of the O-glycoside-based copolymer. PMID- 8459407 TI - Enzyme variation at the aspartate aminotransferase locus in members of the Anopheles gambiae complex (Diptera: Culicidae). AB - The enzyme aspartate aminotransferase (AAT) currently is used to identify Anopheles quadriannulatus Theobald, the animal-biting, nonmalaria vector species of the Anopheles gambiae complex. Samples of An. quadriannulatus from South Africa and An. gambiae Giles s.str. from the island of Grand Comoros and the People's Republic of Congo have shown variation in electromorph frequencies that indicate that AAT has five alleles. The three slowest alleles are found in An. quadriannulatus and the three fastest in An. gambiae, An. arabiensis Patton and An. merus Donitz. One of these is common to both An. quadriannulatus and An. gambiae. This overlap indicates a potential misidentification of 0.3% of unknown females with a further 2.1% being unidentifiable. However, all of the specimens in the overlap area were classified correctly using octanol dehydrogenase (ODH). Variation at the ODH locus in An. quadriannulatus is recorded for the first time, with four of 157 specimens being heterozygous for the fast allele. The probability of both AAT and ODH giving an incorrect or indecisive identification is 0.0005. The slowest AAT alleles were present in samples from a single locality, indicating the lack of gene flow between subpopulations of An. quadriannulatus in close geographic proximity in the Shingwedzi area, South Africa. A modified method for multiple gel casting is given. PMID- 8459406 TI - Structure-activity relationship of glycine betaine analogs on osmotolerance of enteric bacteria. AB - Bacterial cells have the ability to accumulate compatible solutes within the cytoplasm to maintain their osmolarity above that of the extracellular milieu. Glycine betaine (GB) and its biosynthetic precursor choline (Chol) are the major compatible solutes that bacteria accumulate when osmotically challenged. Different osmotically triggered active transport mechanisms have been identified for GB and Chol. In the present study we examined the bioisosteric replacement of the carboxylic group of GB with sulfonic, phosphonic or benzenesulfonamido groups. The sulfonic acid analog (sulfobetaine, compound 3) showed osmoprotectant activity equivalent to that of GB. In addition, we tested the possibility of utilizing GB/Chol transport systems to deliver cytotoxic analogs of GB into three strains of E. coli that differed in their salt resistance. We found that N1 betainyl-N4-(haloacetyl)sulfanilamides (compounds 17c-e) that are GB analogs containing alkylating side chain within their structures inhibited the bacterial growth of the tested standard and salt sensitive strains of E. coli. We also showed that the (N-methyl-cyclic ammonio)methanesulfonates (compounds 21a-c) are able to block Chol transport system in both the standard and the salt-sensitive E. coli strains used. At the concentration used (0.1 mM), none of the tested compounds showed any significant effect on the salt-resistant strain used. PMID- 8459408 TI - Seasonal development of Leptotrombidium pallidum (Acari: Trombiculidae) observed by experimental rearing in the natural environment. AB - Engorged larvae of Leptotrombidium pallidum Nagayo, Miyagawa, Mitamura & Tamiya, the vector mite of scrub typhus in Japan, were reared by feeding them with fresh eggs of the collembolan Sinella curviseta Brook while confined in small plastic containers under natural conditions in a copse. The larvae were collected from wild rodents (Apodemus speciosus) in autumn 1985 and spring 1986. Adults were kept alive for 2 yr or longer. The larvae obtained in autumn became dormant in the cold winter season, and growth recommenced in the spring. Thus, the development of mites collected in April became synchronized with that of larvae obtained in the autumn. Most larvae developed into protonymphs in May, deutonymphs in June, tritonymphs in July, and adults in August. The females laid eggs in two consecutive summers. Some larvae collected in autumn were kept in a refrigerator until the following summer. They developed into deutonymphs, tritonymphs, or adults and then became dormant in the winter. Development restarted the next spring and all became adult by summer, when the females laid eggs. Under experimental conditions, all larvae are hatched in the autumn, unlike the natural situation in which two peaks of larval occurrence on wild rodents are observed in autumn and spring. PMID- 8459409 TI - Midgut basal lamina thickness and dengue-1 virus dissemination rates in laboratory strains of Aedes albopictus (Diptera: Culicidae). AB - Strain differences in midgut basal lamina thickness, assessed by measurement in transmission electron micrographs, and disseminated infection rates of dengue-1 virus were compared among three laboratory strains of Aedes albopictus (Skuse). Mean basal lamina thickness for the New Orleans and Houston strains were significantly greater than those for the Oahu strain, which exhibits a higher disseminated infection rate than the former two. Although basal lamina thickness among the F1 progeny of reciprocal crosses of the Oahu and Houston strains were intermediate between the parental strains, they were too variable to be useful as markers in genetic studies. Measurements of basal laminae among individuals of the New Orleans strain, with disseminated or nondisseminated infections, failed to demonstrate a role for basal lamina thickness as a modulator of dengue-1 virus dissemination across the midgut epithelium of Ae. albopictus. PMID- 8459410 TI - Review of Chrysomya rufifacies (Diptera: Calliphoridae). AB - The taxonomy, distribution, bionomics, and medical and veterinary importance of C. rufifacies are reviewed and summarized. Late instars are beneficial as predators of the maggots of pathogen-transmitting and myiasis-producing flies, but strains from parts of Australia, India, and Hawaii are harmful as secondary myiasis agents. The effects of invasions, possible competition, and displacement of native calliphorids are discussed. The developmental duration of the immature stadia at different temperatures are reviewed. The primary literature (274 papers) dealing with this fly is given and cross-referenced by subject to serve as a reference to research entomologists and governmental agencies involved in the control of this livestock parasite in the Americas and Australia. PMID- 8459411 TI - Effects of preblood-meal sugar on sugar seeking and upwind flight by gravid and parous Aedes aegypti (Diptera: Culicidae). AB - Sugar seeking and upwind flight of gravid and parous female Aedes aegypti (L.) was measured by their attraction to honey in a dual-port airflow olfactometer at selected time intervals after a blood meal. Comparisons were made between pre blood-meal sugar-fed and unfed females. Sugar-fed females had greater total energy reserves, mostly because of elevated lipid levels. Gravid mosquitoes in both groups showed a strong tendency to fly upwind. This appears to be a pre ovipositional response. Gravid female orientation to honey was greater in unfed females than in sugar-fed females. After oviposition, parous females became more strongly attracted to honey, if their honey response was not already high. PMID- 8459412 TI - Antibody development against northern fowl mites (Acari: Macronyssidae) in chickens. AB - This study reports the development of an antibody against protein(s) from the tissue of the northern fowl mite, Ornithonyssus sylviarum (Canestrini & Fanzago). Northern fowl mite proteins were obtained by affinity chromatography and used for immunization. Western blot analysis identified proteins that were reactive with sera from birds immunized with the antigen; this indicated that serum antibodies against the northern fowl mite had been produced. Chickens that had been immunized or infested, or both, with the northern fowl mite produced sera that were reactive with a 100 kilodalton (kD) protein. The response was greater if the chicken had been immunized with the antigen and infested with the northern fowl mite. Experimentally immunized and infested chickens experienced limited decreases in the levels of northern fowl mite infestation. Survival of bloodfed mites after ingestion of the immune chicken blood was assessed in an in vitro feeding study using blood-filled parafilm sacs; minor differences in northern fowl mite feeding tendencies were noted. The chickens developed antibodies to the northern fowl mite proteins, but this immunity did not decrease the infestation level or in vitro feeding. PMID- 8459413 TI - Variation in attractiveness of human subjects to malaria mosquitoes (Diptera: Culicidae) in The Gambia. AB - During experimental hut trials to assess the efficacy of insecticide-treated bednets against malaria mosquitoes, we observed that human subjects varied consistently in their attractiveness to mosquitoes. Attractiveness was assessed by estimating the numbers of wild Anopheles gambiae Giles mosquitoes entering a hut in which a man was sleeping, and the numbers of human-bloodfed An. gambiae sensu lato collected from each hut each morning. Five trials were carried out at Wali Kunda in rural Gambia during 2.5 yr. During each 6-wk trial a man slept under a bednet in each of the six huts. Morning collections of mosquitoes from the room, enclosed verandas, and window traps of each hut provided estimates of the number of mosquitoes that had entered during the night. Blood meals were analyzed using an ELISA technique to identify those mosquitoes feeding on humans. Specimens were collected by field workers, not the subjects; therefore, sampling was independent of the subjects' ability to catch mosquitoes. Moreover, the trials were designed to measure the relative attractiveness of individual sleepers to mosquitoes, allowing for other sources of variation (i.e., among huts, bednets, nights, and day of the week). Attractiveness of men to mosquitoes differed significantly among individuals as indicated by the consistent differences between the numbers of mosquitoes entering each man's hut and the numbers feeding on each man. However, the two measures of attractiveness were apparently independent of each other: subjects who attracted consistently high numbers of vectors into their hut did not necessarily have high numbers of mosquitoes feeding on them. These findings support the view that some individuals within a community are at greater risk from mosquito-borne pathogens than others. PMID- 8459414 TI - Short-term population dynamics of adult Aedes dorsalis (Diptera: Culicidae) in a northern California tidal marsh. AB - Short-term changes in the age structure and abundance of the host-seeking population of Aedes dorsalis (Meigen) females were studied in a Northern California tidal marsh by daily sampling from 25 July through 17 August 1990. The calculated numbers of nulliparous and parous females per day were used to estimate parity rates and duration of the gonotrophic cycle. The numbers of females collected per day ranged from 261 to 74,443, and daily parity rates ranged from 0 to 91%. The overall parity rate was 14%. Two peaks in nulliparous female abundance on days 7 and 12 were followed 5 d later by increases in the number of parous females, indicating that two cohorts had emerged with gonotrophic cycle lengths of approximately 5 d. This is consistent with the 5-d gonotrophic cycle length estimated using time series analysis of the same data sets. Peak host-seeking activity of nulliparous females in the two cohorts occurred 16 d after two marsh systems were flooded by monthly high tides. Survivorship was estimated to be 14% per gonotrophic cycle and 67% per day, although emigration may have caused the substantial underestimation of actual survivorship. PMID- 8459415 TI - Blood feeding and autogeny in the peridomestic mosquito Aedes bahamensis (Diptera: Culicidae). AB - Under laboratory conditions, most colony and field-collected Aedes bahamensis Berlin females developed eggs autogenously when they had access to sugar. However, significantly fewer starved females were autogenous, and they produced smaller egg clutches. Autogenous fecundity covaried with wing length, and smaller females generally failed to express autogeny. Mating had no effect on the maturation of the initial egg clutch. Most starved, nulliparous females blood fed from a restrained host. At a south Florida field site, both parous and nulliparous Ae. bahamensis were captured with a power aspirator, but concurrent sampling with dry ice-baited, light traps collected only parous females. Host seeking females, taken either in chicken-baited traps or as they attempted to blood feed on humans, were also parous, with a single exception. Thus, at this field site, Ae. bahamensis females normally delayed blood feeding until after their first oviposition. Whether or not Ae. bahamensis females in other south Florida populations show a similar gonotrophic pattern probably will depend upon the availability of sugar sources and conditions in the mosquito's aquatic habitat that affect adult size. PMID- 8459416 TI - Distribution of western equine encephalomyelitis virus in the alimentary tract of Culex tarsalis (Diptera: Culicidae) following natural and artificial blood meals. AB - The distribution of western equine encephalomyelitis (WEE) virus in the alimentary tract of Culex tarsalis (Coquillett), following blood feeding, was examined using autoradiography. Following engorgement on chicks circulating radiolabeled virus, WEE virus in all mosquitoes was concentrated at the margins of the abdominal midgut, adjacent to the epithelium. Thirty percent of mosquitoes also contained small amounts of virus in the foregut, ventral diverticulum, and/or thoracic midgut. Mosquitoes imbibing labeled virus in hanging drops containing washed blood cells and sucrose showed an altered distribution of WEE virus. Virus was not concentrated adjacent to the abdominal midgut epithelium, and all mosquitoes contained large amounts of WEE virus in most regions of the thoracic alimentary tract. These findings may help explain the increased thresholds of infection associated with artificial feeding techniques and indicate that artificial blood meals may alter the sites of initial arbovirus infection within the alimentary tract of mosquito vectors. PMID- 8459417 TI - Vector competence of alpine, Central Valley, and coastal mosquitoes (Diptera: Culicidae) from California for Jamestown Canyon virus. AB - Mosquitoes collected from alpine, Central Valley, and coastal habitats in California were evaluated for their vector competence for four strains of Jamestown Canyon (JC) virus. Three of the viral strains examined were isolated from alpine Aedes species collected in California, and one, the prototype JC virus, was isolated from Culiseta inornata (Williston) collected in Colorado. Alpine Aedes tahoensis Dyar, Ae. cataphylla Dyar, Ae. hexodontus Dyar, Ae. increpitus Dyar, Ae. clivis Lanzaro and Eldridge, and coastal Aedes washinoi Lanzaro and Eldridge were variably susceptible to alpine strains of JC virus. Infection rates ranged from 22 to 77%, and peroral transmission rates of the infected females ranged from 0 to 26%. The differences were related to both mosquito species and viral strain. Coastal populations of Cs. inornata, Ae. washinoi, and Ae. sierrensis (Ludlow) were incompetent vectors when fed an alpine strain of JC virus, whereas Ae. squamiger (Coquillet) and Ae. dorsalis (Meigen) were competent vectors. Peroral transmission rates following parenteral infection of females of most species were about twofold higher than those for perorally infected females. A population of Cs. inornata from the Central Valley was highly susceptible when fed an alpine strain of JCV and transmitted virus both horizontally and vertically. Alpine strains of JC virus also were transmitted vertically by Ae. tahoensis, Ae. washinoi, and Ae. squamiger following parenteral infection of females. PMID- 8459418 TI - Enzyme polymorphism and genetic variability of one colonized and several field populations of Phlebotomus papatasi (Diptera: Psychodidae). AB - The Alexandria laboratory colony and five field populations of Phlebotomus papatasi (Scopoli) from Egypt were analyzed for genetic variation at 17 enzyme loci. The laboratory colony was characterized by a low level of genetic variation as measured by the average number of alleles per locus (A = 1.70 +/- 0.16) and the average expected heterozygosity (He = 0.06 +/- 0.02). Polymorphism was observed at 23.5% of the examined loci, and genotype frequencies at two loci (PGM, AK-2) were found to deviate slightly from the Hardy-Weinberg equilibrium. In contrast, the average number of alleles per locus for field populations ranged from A = 2.35 +/- 0.20 to 2.76 +/- 0.10, and He ranged from 0.15 +/- 0.03 to 0.21 +/- 0.05. All loci of field populations exhibited polymorphism, ranging from 47.0% to 76.5%, and four to seven loci in each population were found to deviate from the Hardy-Weinberg equilibrium. Deviations in both colonized and field populations were caused by heterozygote deficiency. Despite geographic isolation and some individual deviations from the Hardy-Weinberg equilibrium, no evidence of significant genetic difference was obtained for any of the populations sampled. Calculated indices of genetic distance and genetic identity for the five field populations showed minor variation but were collectively representative of a single, genetically uniform population. PMID- 8459420 TI - Mode of action of pyriproxyfen and methoprene on eggs of Ctenocephalides felis (Siphonaptera: Pulicidae). AB - Adult cat fleas were exposed to residues of pyriproxyfen and methoprene in glass vials, then fed on a cat 24 h later to investigate the mode of action of juvenoid growth regulators on embryonic development in flea eggs. Eggs laid by pyriproxyfen-treated fleas within 70 h after exposure to this juvenoid were often devoid of yolk and frequently collapsed after oviposition. Minimal amounts of yolk were deposited in eggs laid after 70 h, and no blastoderm was formed. These results are significant because both modes of action were different than those observed earlier by investigators studying ovicidal effects in adult insects treated with juvenile hormone. In contrast to the pyriproxyfen results, eggs laid by methoprene-treated fleas showed no gross morphological effects, and these eggs remained turgid during embryogenesis. However, the eggs either did not hatch or the larvae died within hours after hatching. Histological examination of the eggs revealed that most of the eggs contained segmented embryos which had apparently died during blastokinesis. Although eggs of some insects exposed to juvenile hormone during oogenesis fail to undergo germ band formation, there was no evidence of this effect in methoprene-treated cat fleas. PMID- 8459419 TI - Individual variation within breeds of beef cattle in resistance to horn fly (Diptera: Muscidae). AB - Weekly estimates of populations of horn fly, Haematobia irritans (L.), were made on individual purebred Charolais, Chianina, Hereford, Polled Hereford, and Red Poll cows in 1988, 1989, and 1990 with Angus included in 1989 and 1990. During the study period, 94 of approximately 200 individual cows were classified as either fly resistant or fly susceptible. In general, individuals retained the same classification over the 3-yr study period. The mean number of flies on individual susceptible cows in all breeds was at least twice the number of flies on resistant cows. Susceptible Chianina cows averaged > 4.5 times as many flies as resistant cows of the same breed. Individual cows within all breeds classified as fly resistant ranged in age from 2 to 12 yr, whereas fly-susceptible cows ranged in age from 2 to 14 yr; therefore, cow age did not influence the abundance of horn flies on individual cows within breeds. Two-year-old fly-resistant cows were identified accurately according to their horn fly-population density, showing the potential of host resistance in horn fly-population management. PMID- 8459421 TI - Dispersal of the sand fly Lutzomyia longipalpis (Diptera: Psychodidae) at an endemic focus of visceral leishmaniasis in Colombia. AB - Mark-release-recapture studies were carried out during 1990-1991 in El Callejon, Colombia, an endemic focus of American visceral leishmaniasis, to study the longevity, dispersal, and flight range of the principal vector, Lutzomyia longipalpis Lutz & Neiva. Several groups of wild-caught (n = 1,539) and laboratory-reared F1 (n = 2,208) sand flies were marked with fluorescent dusts and released. Recaptures at daytime resting sites, on animal bait, and in CDC light traps were made for 20 d following each release. From 2 to 9% of L. longipalpis were recaptured, a rate which differed between the sexes (7.7% male, 1.5% female). Overall, 49% of the L. longipalpis were recaptured between 0 and 50 m, 48% within 100 and 300 m, and nearly 3% at > or = 0.5 km from the release site. Sex differences in recapture site, distance flown, and direction were observed. Our results indicate that the dispersal behavior of peridomestic populations of L. longipalpis compares more closely with that of Old World sand fly species from similar habitats than to the sylvan Neotropical phlebotomines. PMID- 8459422 TI - Dynamics of a mathematical model of Chrysomya megacephala (Diptera: Calliphoridae). AB - The laboratory population dynamics of Chrysomya megacephala (F.) was explored with a mathematical model of density-dependent growth. Fecundity and survival decreased significantly as a function of larval density. Parameters in the exponential regressions fitted to the fecundity and survival data were incorporated into a finite-difference equation that incorporates the delayed effect of larval density on fecundity and survival of adults. The theoretical population model of C. megacephala showed cyclic behavior with a stable limit cycle of two points for adults and immatures. PMID- 8459423 TI - Environmental temperature on the vector competence of Culex univittatus (Diptera: Culicidae) for West Nile virus. AB - The effects of the extrinsic incubation temperature on the vector competence of Culex univittatus Theobald for West Nile (WN) virus were studied. A mean titer of 7.0 log10 CPD50/ml of mosquito suspension was reached in orally infected mosquitoes after 11, 15, and 16 d of incubation at 26 and 30 degrees C and at fluctuating temperatures in an outside cage (mean temperature, 23.5 degrees C), respectively. In contrast, 22 and 58 d were required to reach the same titers at 18 and 14 degrees C, respectively. Transmission rates of 100% were reached after 58 d (14 degrees C), 22 d (18 degrees C), and 15 and 16 d (30 degrees C and outside). Except at 30 degrees C, transmission rates fluctuated; e.g., at 18 degrees C from day 19, the transmission rate was 80-100%, whereas at 14 degrees C on day 36, the transmission rate was 60% and thereafter 20-100%. The maximum transmission rate occurred concurrently with maximum titers of virus secreted into capillary tubes during in vitro transmission attempts. Mosquito longevity increased as incubation temperature decreased and was maximum at 114 d at 14 degrees C. Mosquitoes that were transferred from 14 to 26 degrees C after 49 d subsequently oviposited, engorged on a pigeon, and transmitted virus, which indicated the possibility for overwintering of WN virus in adult Cx. univittatus. Vector competence at outside cycling temperatures was intermediate between that at 26 and 30 degrees C, indicating that incubation at 26 degrees C would give a fair reflection of the vector competence of Cx. univittatus during the summer near Johannesburg. Two human epidemics of WN virus are reevaluated in the light of these results; it is concluded that, in addition to abnormal rainfall, higher than normal temperatures were important factors for their occurrence. PMID- 8459424 TI - Feeding Haematobia irritans (Diptera: Muscidae) adults through a nylon-reinforced silicone membrane. AB - A nylon-reinforced silicone membrane used to feed Haematobia irritans (L.) adults was found to be equally effective as the currently used blood-soaked cotton method. Membranes consisted of nylon bridal veil embedded in a thin layer of clear silicone caulk prepared by pressing bridal veil and silicone caulk bead between two brass rollers, using Parafilm and office paper as support materials. Membrane thickness was regulated by varying the space between the brass rollers. Feeding success was measured by adult survival, fecundity, and fertility during 10-d experimental periods. Adults fed successfully through 0.02-, 0.03-, and 0.06 mm-thick membranes, but not 0.08- and 0.11-mm-thick membranes. More larvae were produced by flies that were presented the rough surface than the smooth surface if the membranes were 0.03 or 0.06 mm thick. Similarly, female and male survival was higher when the rough membrane surface was presented. Female survival was unaffected by thickness (between 0.02 and 0.06 mm), whereas male survival decreased as thickness increased. Membranes that were 0.03 and 0.06 mm thick leaked at a greater rate if the smooth surface was presented to the flies, and 0.02-mm-thick membranes leaked regardless of the surface presented. When adults were maintained at a density of 0.42 fly per cm3, larval production was maximized when 22 flies were feeding per 1.0 cm2 of membrane surface. It was not possible to determine the optimum fly density per 1.0 cm2 of membrane surface when flies were maintained at a density of 0.10 fly per cm3. PMID- 8459425 TI - Temperature- and humidity-dependent longevity of unfed adult Hyalomma truncatum (Acari: Ixodidae). AB - The survival of unfed adult Hyalomma truncatum Koch held under different regimes of constant temperature (5, 17, 24, and 30 degrees C) and relative humidity (10, 50, and 80%) was monitored during > 1 yr. Longevity of this medically important African tick was shortest at the highest temperature and lowest relative humidity (100% dead at week 25). Conversely, H. truncatum lived longest at lower temperatures and higher relative humidity (< 100% dead at week 64). The combined effects of temperature and humidity, measured as vapor pressure deficit, were strongly related to survival of these ticks. The survival of males and females was similar and was independent of the weight of ticks. These findings have implications for the maintenance and study of laboratory colonies of H. truncatum and for the development of tick control strategies to reduce vectorial capacity. PMID- 8459426 TI - Effect of salt marsh drainage on the distribution of Tabanus nigrovittatus (Diptera: Tabanidae). AB - Immature stages of Tabanus nigrovittatus Macquart inhabit salt marsh sod. A study of the distribution of larvae in relation to the presence or absence of surface water showed that larval densities were higher in salt marsh areas that appeared well drained. Late instars remained above the sod surface more frequently in laboratory conditions mimicking high water-table levels. The development of anaerobic conditions in sod at high water levels probably deterred larvae from burrowing into the sod. Therefore, mosquito control ditches, constructed to augment interstitial drainage inadvertently may have created optimal tabanid larval habitat. PMID- 8459427 TI - Breeding structure of screwworm fly populations (Diptera: Calliphoridae) in Colima, Mexico. AB - Starch gel electrophoresis was used to resolve gene frequencies among populations of screwworm, Cochliomyia hominivorax (Coquerel). The loci examined coded for alpha-glycerophosphate dehydrogenase, octanol dehydrogenase, and phosphoglucomutase. Flies were sampled by traps widely distributed in Colima Province, southwestern Mexico. Gene frequencies at Odh differed significantly among the 11 populations. Alleles segregating at Pgm and alpha-Gpdh were homogeneous among populations. There were significant departures from random mating within populations, but no genetic differentiation among populations was detected. The data suggest unrestricted gene flow among populations. Departures from random mating within populations were explained by the pooling of samples from separate breeding units. PMID- 8459428 TI - Different developmental strategies in two boreal blow flies (Diptera: Calliphoridae). AB - The minimum developmental rates of Protophormia terraenovae (Robineau-Desvoidy) and Calliphora vomitoria (L.) were measured at four temperatures: 12.5, 23, 29, and 35 degrees C. Although both species are Holarctic in distribution and hemisynanthropic, there are important differences in the response of their developmental stages to various temperature regimes. The eggs and feeding larvae of P. terraenovae responded linearly to temperatures from 23 to 35 degrees C, but development was retarded at 12.5 degrees C. The feeding larvae took about 11 times longer to develop at 12.5 than at 23 degrees C, indicating poor cold adaptation. The converse is true of C. vomitoria, which took only 2 times as long at 12.5 than at 23 degrees C but failed to complete development at 29 and 35 degrees C. Our laboratory data and field studies of others suggest that, in nature, P. terraenovae and C. vomitoria prefer breeding in larger carcasses as a survival tactic and means of extending their distribution into colder regions. PMID- 8459429 TI - Location of tick (Acari: Ixodidae) attachment sites on humans in North Carolina. AB - The location of tick attachment sites on humans was determined by information provided by respondents to a questionnaire, and by submission of ticks, in counties that have historically had a high incidence of Rocky Mountain spotted fever in North Carolina. Information was gathered from May through September in 1989, 1990, and 1991. Dermacentor variabilis (Say) made up 94% of the collections. Most (50%) were taken from the head; a sizable portion was removed from the legs (22%). The epidemiological implications and potential use of this information in a public information campaign are discussed. PMID- 8459430 TI - Genetic variation in a Tanzanian population of Glossina swynnertoni (Diptera: Glossinidae). AB - Adult Glossina swynnertoni Austen that emerged from puparia collected during 1989 and 1991 near Makuyuni, Tanzania, were examined by polyacrylamide gel electrophoresis. Fourteen of 17 enzymes were monomorphic. Midgut alkaline phosphatase (ALKPH), phosphoglucomutase (PGM), and glucose-6-phosphate isomerase (PGI) from the head and thorax were polymorphic. Banding patterns indicated that the locus for PGM was on the X chromosome and loci for ALKPH and PGI were autosomal. For the 17 loci studied, the mean heterozygosity per locus was 6.1 +/- 3.7% in the 1989 sample and 5.7 +/- 3.7% in the 1991 sample. The effective number of alleles per locus was 1.11 and 1.10 in these samples. This level of genetic variation was low compared with other populations of tsetse flies and indicated that the sample may have been drawn from a small inbred population or one that recently had gone through a genetic bottleneck. PMID- 8459431 TI - Experimental vector incompetence of a soft tick, Ornithodoros sonrai (Acari: Argasidae), for Crimean-Congo hemorrhagic fever virus. AB - Adults and nymphs of a soft tick, Ornithodoros sonrai Sautet & Witkowski, were allowed to feed on suckling mice that had been experimentally infected with Crimean-Congo hemorrhagic fever (CCHF) virus (IbAr 10200 strain). The mean viral titer of mouse blood at the time of tick feeding was 10(3.2) plaque-forming units (PFU) per ml. Samples of ticks were assayed on 12 occasions between days 0 and 31 after the viremic blood meal. Mean CCHF viral titers were 10(2.1) PFU per tick immediately after the viremic meal but declined to 10(1.2) PFU per tick after 2 d, and no virus was detected beyond 8 d. The percentage of ticks with detectable virus was 92% (22/24) immediately after the viremic meal, but then declined to 20% (2/10) after 4 d and to 0% (0/44) after 11 or more days. Ticks were allowed to feed on sets of three naive suckling mice on days 0, 2, 5, 8, 11, 14, 21, and 28 after the viremic blood meal, but CCHF viral transmission did not occur. Similarly, no transovarial transmission of virus from CCHF virus-exposed O. sonrai to their progeny was observed. These results strongly indicate that O. sonrai is not a vector of CCHF virus. PMID- 8459432 TI - The European Convention on bioethics. AB - Benefiting from a widely recognised experience of the field of bioethics, the Council of Europe which represents all the democratic countries of Europe, has embarked on the ambitious task of drafting a European Convention on bioethics. The purpose of this text is to set out fundamental values, such as respect for human dignity, free informed consent and non-commercialisation of the human body. In addition to this task, protocols will provide specific standards for the different fields concerned with the application of biomedical sciences. The convention and the first two protocols (human experiments and organ transplants) are due to be ready for signature by mid 1994. PMID- 8459433 TI - After bioethics and towards virtue? AB - The place of philosophical medical ethics in medical education and clinical practice has recently been questioned. Although partially valid, the criticisms do not warrant abandoning the enterprise. Instead a reappraised model, based on Aristotelean concepts of intellectual and moral virtue is suggested. PMID- 8459434 TI - A critique of using age to ration health care. AB - Daniel Callahan has argued that economic and social benefits would result from a policy of withholding medical treatments which prolong life in persons over a certain age. He claims 'the real goal of medicine' is to conquer death and prolong life with the use of technology, regardless of the age and quality of life of the patient, and this has been responsible for the escalation of health care expenditure. Callahan's proposal is based on economic rationalism but there is little evidence to suggest that substantial economic savings could be achieved. Moreover, his argument raises serious moral objections. A policy of withholding treatments from members of a social group involves elements of compulsion and discrimination, both of which would intrude on the doctor-patient relationship, undermine the autonomy of elderly patients, and invoke the slippery slope towards involuntary forms of euthanasia. Life-death decisions should be based on more than the one criterion of age, and take account of more relevant factors such as the patient's usual state of well-being, her/his expressed wishes, informed consent and the type of illness. Any move to the implementation and enforcement of the policy Callahan recommends would be rejected by health professionals and the public. PMID- 8459435 TI - The medical ethics of the 'father of gynaecology', Dr J Marion Sims. AB - Vesico-vaginal fistula (VVF) was a common ailment among American women in the 19th century. Prior to that time, no successful surgery had been developed for the cure of this condition until Dr J Marion Sims perfected a successful surgical technique in 1849. Dr Sims used female slaves as research subjects over a four year period of experimentation (1845-1849). This paper discusses the controversy surrounding his use of powerless women and whether his actions were acceptable during that historical period. PMID- 8459436 TI - Biomedical ethics in Europe--a need for the POBS? PMID- 8459437 TI - The disposal of the aborted fetus--new guidelines: ethical considerations in the debate in Sweden. AB - During the 70s and 80s ethical debate concerning the fetus became intensive. The great advances made in medical technology and research and improvements in prenatal diagnosis as well as in embryological research have led us to believe that the fetus is an individual with recognised claims to protection. In Sweden the aborted fetus has previously been considered merely as a risk-disposal problem, equivalent to dangerous and infected material and there have been no specific guidelines for the treatment of the fetus after abortion. In July 1990 treatment of aborted fetuses was changed with the general guidelines from the National Board of Health and Welfare. The present paper sets out the main contents of the guidelines and discusses the gradually changing views concerning the status of the human fetus in Sweden, as well as the public debate which has been a contributing factor to these changes. PMID- 8459438 TI - The relevance of health state after treatment in prioritising between different patients. AB - In QALY-thinking, an activity that takes N people from a bad state (including 'dying') to the state of healthy for X years should have priority over an activity that takes N other people from the same bad state to a state of moderate illness for the same number of years (given equal costs). An empirical study indicates that this view may not be shared by the general public in Norway. Subjects tended to emphasise equality in value of life and in entitlement to treatment rather than level of health after treatment. The relevance of costs per QALY in prioritising between different health care programmes in Norway is thereby brought in to doubt. While the sample in the study is too small to support firm policy conclusions, the results should contribute to an increased interest among health economists in actually measuring people's ethical preferences in matters of prioritising, rather than taking it for granted that their own values are shared by the general public. PMID- 8459439 TI - What counts as success in genetic counselling? AB - The question of what counts as a successful outcome of the process of genetics counselling has recently become central because of the increasing calls for efficiency in health care, and for means of measuring efficiency. Angus Clarke has drawn attention to this trend, and has argued against both a measure in terms of the number of terminations of pregnancy performed as a result of counselling, and an assessment in terms of the contribution of genetics counselling to a national eugenics policy. He suggests instead a measure of workload. There are good arguments for supporting Clarke's position up to a point. In looking for an appropriate measure, much turns on how genetics counselling is defined. It is here understood in the context of an autonomy model of health care. It is argued that there is a contradiction between such an interpretation and the termination measure of outcome. The political philosophy underlying this outcome is also defective. Workload is not sufficient as a measure of outcome however; it is essential to look at the proper goals of an activity. It is argued that these must be connected in some way with the genetic health of the population; that the promotion of reproductive autonomy itself is not sufficient as a goal. The concern for genetic health, however, is interpreted in a way that avoids Clarke's concerns about a national eugenics policy. PMID- 8459440 TI - International bioethics? The role of the Council of Europe. PMID- 8459441 TI - Avoiding a reductionist stance. PMID- 8459442 TI - Patients' rights and publication. PMID- 8459443 TI - Classical medicine v alternative medical practices. PMID- 8459444 TI - Medical ethics in the European Community. AB - Increasing European co-operation must take place in many areas, including medical ethics. Against the background of common cultural norms and pluralistic variation within political traditions, religion and lifestyles, Europe will have to converge towards unity within the field of medical ethics. This article examines how such convergence might develop with respect to four major areas: European research ethics committees, democratic health systems, the human genome project and rules for stopping futile treatments. PMID- 8459446 TI - Potassium channels in squid neuron cell bodies: comparison to axonal channels. AB - The squid giant axon is formed from the fusion of many axons whose cell bodies are located in the giant fiber lobe (GFL) of the stellate ganglion. We measured macroscopic potassium channel currents in both squid giant axons and in the cell bodies. These currents appear similar in many ways, but were differently affected by the amino group modifying reagent, trinitrobenzene sulfonic acid (TNBS). TNBS increased the steady-state amplitude of the axonal currents but decreased the somal currents. We also studied single K channel currents in the giant fiber lobe cells, for comparison with single K channel currents measured previously in the axons. We found two common classes of K channels, distinguished by their conductances (11 and 25 pS) and kinetic properties. The two channel types resemble the 10 and 20 pS channels that have been described in squid giant axons. These results suggest that the cell bodies and axons express fundamentally similar K channel types. The different effects of amino group modification on macroscopic K currents in the two regions may arise from small (perhaps posttranslational) modifications of the core proteins. PMID- 8459445 TI - The topological analysis of integral cytoplasmic membrane proteins. AB - We review three general approaches to determining the topology of integral cytoplasmic membrane proteins. (i) Inspection of the amino acid sequence and use of algorithms to predict membrane spanning segments allows the construction of topological models. For many proteins, the mere identification of such segments and an analysis of the distribution of basic amino acids in hydrophilic domains leads to correct structure predictions. For others, additional factors must come into play in determining topology. (ii) Gene fusion analysis of membrane proteins, in many cases, leads to complete topological models. Such analyses have been carried out in both bacteria and in the yeast Saccharomyces cerevisiae. Conflicts between results from gene fusion analysis and other approaches can be used to explore details of the process of membrane protein assembly. For instance, anomalies in gene fusion studies contributed evidence for the important role of basic amino acids in determining topology. (iii) Biochemical probes and the site of natural biochemical modifications of membrane proteins give information on their topology. Chemical modifiers, proteases and antibodies made to different domains of a membrane protein can identify which segments of the protein are in the cytoplasm and which are on the extracytoplasmic side of the membrane. Sites of such modifications as glycosylation and phosphorylation help to specify the location of particular hydrophilic domains. The advantages and limitations of these methods are discussed. PMID- 8459447 TI - Hypotonically induced changes in the plasma membrane of cultured mammalian cells. AB - Cells from three cell lines were electrorotated in media of osmotic strengths from 330 mOsm to 60 mOsm. From the field-frequency dependence of the rotation speed, the passive electrical properties of the surfaces were deduced. In all cases, the area-specific membrane capacitance (Cm) decreased with osmolality. At 280 mOsm (iso-osmotic), SP2 (mouse myeloma) and G8 (hybridoma) cells had Cm values of 1.01 +/- 0.04 microF/cm2 and 1.09 +/- 0.03 microF/cm2, respectively, whereas dispase-treated L-cells (sarcoma fibroblasts) exhibited Cm = 2.18 +/- 0.10 microF/cm2. As the osmolality was reduced, the Cm reached a well-defined minimum at 150 mOsm (SP2) or 180 mOsm (G8). Further reduction in osmolality gave a 7% increase in Cm, after which a plateau close to 0.80 microF/cm2 was reached. However, the whole-cell capacities increased about twofold from 200 mOsm to 60 mOsm. L-cells showed very little change in Cm between 280 mOsm and 150 mOsm, but below 150 mOsm the Cm decreased rapidly. The changes in Cm correlate well with the swelling of the cells assessed by means of van't Hoff plots. The apparent membrane conductance (including the effect of surface conductance) decreased with Cm, but then increased again instead of exhibiting a plateau. The rotation speed of the cells increased as the osmolality was lowered, and eventually attained almost the theoretical value. All measurements indicate that hypo-osmotically stressed cells obtain the necessary membrane area by using material from microvilli. However, below about 200 mOsm the whole-cell capacities indicate the progressive incorporation of "extra" membrane into the cell surface. PMID- 8459448 TI - Regulation of epithelial shunt conductance by the peptide leucokinin. AB - Isolated Malpighian tubules of the yellow fever mosquito Aedes aegypti spontaneously secrete NaCl, KCl and water across an epithelium of modest transepithelial resistance (40-80 omega cm2) and high transepithelial voltage (30 70 mV, lumen positive). Transepithelial electrochemical potentials indicate that Na and K are secreted by active and Cl by passive transport mechanisms. The addition of synthetic leucokinin-VIII (LK-VIII, insect myotropic peptide) to the peritubular bath significantly increases the rates of transepithelial NaCl, KCl and water secretion. In parallel, LK-VIII depolarizes the transepithelial voltage from 59.3 to 5.7 mV, decreases the transepithelial resistance from 57.7 to 9.9 omega cm2, and renders the basolateral and apical membrane voltages nearly equipotential (approximately -90 mV). Unilateral step changes of the [Cl] in the peritubular bath or tubule lumen elicit small transepithelial Cl diffusion potentials in the absence of LK-VIII but large transepithelial Cl diffusion potentials, up to 85% of Nernst equilibrium potentials, in the presence of LK VIII. In Malpighian tubules treated with dinitrophenol for estimates of the shunt resistance Rsh, LK-VIII reduces Rsh from 52.5 to 5.8 omega cm2. Bilateral reductions of the Cl concentration in tubule lumen and peritubular bath fully restore Rsh to 55.8 omega cm2 in the presence of LK-VIII. LK-VIII has no effects when presented from the luminal side. These results suggest that LK-VIII increases the Cl conductance of the epithelial shunt via a receptor located at the basolateral side of the epithelium. PMID- 8459449 TI - Modulation by Mg2+ and ADP of ATP-sensitive potassium channels in frog skeletal muscle. AB - The patch-clamp technique was used to examine the action of intracellular magnesium ions and ADP in the absence of ATP on skeletal muscle ATP-sensitive potassium channels (K-ATP channels). Inside-out patches were excised from the membrane of sarcolemmal blebs which arise spontaneously without enzymatic treatment after a frog muscle fiber is split in half. In the absence of nucleotides, K-ATP channel open probability was not significantly affected by intracellular magnesium even at a concentration (20 mM) which fully blocks cardiac and pancreatic K-ATP channels. On the other hand, Mg2+ ions (10-20 mM) decreased both inward and outward unitary currents. The percent reduction in inward currents (about 8%) was independent of voltage while the reduction in outward currents was larger at higher voltages, suggesting that the former effect resulted from cancellation of surface charges and the latter from rapid channel block. With or without Mg2+, intracellular ADP could either stimulate or inhibit K-ATP channel activity. Low concentrations (1-100 microM) of ADP rapidly and reversibly increased average activity by a factor of 2 to 3. This activation was seen in half of the patches tested and was greater in the presence of mM Mg2+. High concentrations (> 100 microM) of ADP inhibited activity with a half-block concentration of 450 microM in 0 Mg2+, i.e., more than an order of magnitude the value for ATP. ADP inhibition, like ATP inhibition, was partially relieved by mM Mg2+, suggesting that the Mg(2+)-bound ADP forms are less effective than free ADP forms. During exercise, free ADP levels rise and ATP declines while remaining high.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8459450 TI - An ultrastructural study of the dorsal lingual epithelium of the crab-eating frog, Rana cancrivora. AB - The amphibian tongue contains two types of papilla which are believed to function in gustation and in the secretion of salivary fluid. Scanning electron microscopy reveals that columnar, filiform papillae are compactly distributed over nearly the entire dorsal surface of the tongue of the frog, Rana cancrivora, and fungiform papillae are scattered among the filiform papillae. Microridges and microvilli are distributed on the epithelial cell surface of the extensive area of the filiform papillae. Light microscopy shows that the apex of each filiform papilla is composed of stratified columnar and/or cuboidal epithelium and its base is composed of simple columnar epithelium. Transmission electron microscopy reveals that most of the epithelium of the filiform papillae is composed of cells that contain numerous round electron-dense granules 1-3 microns in diameter. Cellular interdigitation is well developed between adjacent cells. On the free surface of epithelial cells, microridges or microvilli are frequently seen. Between these granular cells, a small number of ciliated cells, mitochondria-rich cells and electron-lucent cells are inserted. In some cases, electron-dense granules are present in the ciliated cells. At higher magnification, the electron dense granules appear to be covered with patterns of spots and tubules. Overall, the morphology and ultrastructure of the lingual epithelium of the three species of Rana that have been studied are quite similar, but they can be easily distinguished from those of Bufo japonicus. Therefore, it appears that lingual morphology is phylogenetically constrained among members of the predominantly freshwater genus Rana to produce uniformity of papillary structure and this morphology persists in Rana cancrivora despite the distinct saline environment in which it lives. PMID- 8459451 TI - Falciparum malaria in naturally infected human patients: I. Ultrastructural differences between malaria pigments in intraerythrocytic asexual and sexual forms. AB - Venous blood samples were taken from patients naturally infected with the human malaria parasite Plasmodium falciparum. Two types of malaria pigment (MP) particles have been demonstrated in intraerythrocytic asexual forms (trophozoites and schizonts), while a single type was detected in gametocytes. Type I MP particles, found in both asexual and sexual forms, are electron-dense. It is suggested that these are proteinaceous and may be intermediate, utilizable metabolic products that serve as a food reserve during development of the parasite in the human host and also during the growth cycle of the sexual form in the mosquito. In asexual forms, type I particles occur within food vacuoles (FV) containing semidigested hemoglobin (Hg), while they are unenveloped in the cytoplasm of the sexual forms. Type II MP particles, found in electron-lucent residual bodies, are crystalloid and of low electron density. It is suggested that these are the final, waste product of Hg digestion in the asexual forms. PMID- 8459452 TI - Falciparum malaria in naturally infected human patients: II. Ultrastructural alterations to erythrocytes infected with asexual forms. AB - Ultrastructural alterations of human erythrocytes infected with asexual forms of Plasmodium falciparum were studied in naturally infected Saudi patients. These included surface knobs and nodules as well as invaginations associated with cytoplasmic vesicles observed in erythrocytes infected with asexual forms of the parasites. Such nodules and surface invaginations have been previously described only in erythrocytes infected with P. ovale and P. vivax, respectively. Within the cytoplasm of infected erythrocytes were membrane-bound clefts, similar to those that appear to be a common characteristic in all red cells infected with malaria parasites. Vacuolations were often seen in the peripheral cytoplasm and may represent hemolyzed areas. Collapsed cells with an internal-lucent interior and surrounded by an irregularly folded membrane may represent completely hemolyzed erythrocytes. PMID- 8459453 TI - A microscopic investigation of the lymphoid organs of the beluga, Delphinapterus leucas. AB - Lymphoid organs from belugas, Delphinapterus leucas, ranging in age from less than one to 16 years, were harvested during a sanctioned hunt to investigate morphology. The spleen is divisible into red and white pulp and a stroma consisting of a reticular network, a collagenous capsule, and trabeculae containing smooth muscle bundles. White pulp areas appear to be devoid of follicles and consist mainly of periarteriolar lymphatic sheaths (PALS), that are larger in younger than in older belugas. Definitive marginal zones between red and white pulp are difficult to discern in older belugas. Lymph nodes are similar to those of other mammals; they possess a follicular cortex surrounding a vascular medulla composed of lymphatic cords and sinuses. Smooth muscle is abundant in the medullary region, usually in close proximity to sinuses. The expansive nodular mass at the root of the mesentery, often referred to as the "pseudopancreas," is similar to lymph nodes in microscopic architecture. Pharyngeal tonsils and gut-associated lymphoid tissue (GALT) are found along the digestive tract and display an "active" morphology. Tonsils are comprised of lobules of follicles separated by vascular connective tissue. Epithelial-lined crypts communicate with the pharyngeal lumen. GALT consists of diffuse and follicular lymphocytes within the intestinal mucosa and submucosa. The thymus is well developed in the younger belugas, with lobules divisible into densely packed cortical zones of thymocytes and more loosely arranged medullary lymphocytes. Hassall's corpuscles are occasionally visible within the medulla. Cetaceans diverged evolutionarily from other mammals over 55 million years ago. This study investigates changes in lymphoid organ morphology in a species that now inhabits a unique ecological niche. This study also lays the groundwork for functional investigation of the beluga immune system, particularly as it relates to differences between healthy and stranded animals. PMID- 8459454 TI - Effects of axial dynamization on bone healing. AB - The effects of early dynamization (physiologic axial compression) on canine fracture healing at six weeks were studied. Bilateral transverse mid-tibial osteotomies were created and initially stabilized with a 2-mm gap using relatively rigid external fixators. Seven days after osteotomy, the telescoping mechanism of one of the fixators on each dog was released (dynamized), resulting in physiologic loading of the osteotomy, while the contralateral fixator remained locked as a rigid control. The dynamized osteotomy closed, and increased functional weight bearing resulted from 3 weeks on. Radiographically the amount of periosteal callus increased over time, but no difference in callus size was seen between the dynamized fractures and the controls. Torsional mechanical testing found the dynamized osteotomies to be significantly stiffer, and they tended to tolerate more maximum torque than the controls. Microscopic evaluation found no difference in the volume of the periosteal and endosteal calluses or in the tissues constituting them. However, a significantly greater proportion of the dynamized osteotomy gap was filled with new bone. These results suggest that dynamization in this delayed union model improved fracture healing by reducing fracture gap size and increasing weight bearing, not by altering the pathway of fracture healing. PMID- 8459455 TI - Traumatic versus postischemic induction of oxidative stress in rat liver. AB - A series of experiments was performed to characterize the effects of tissue trauma, extracellular calcium concentration, and prior ischemia on oxidative stress, measured by the accumulation of malondialdehyde-like materials (MDA-LM) in slices of rat liver. Liver tissue was rendered ischemic for 1 hour at 37 degrees C, either minced (to create traumatized fragments) or cleanly cut and washed (to create nontraumatized fragments), and then reoxygenated for 30 minutes in flasks of buffered salt solution. Nonischemic tissue was incubated similarly but without the 60-minute prior ischemia. The production of MDA-LM in the tissues was used as an indicator of lipid peroxidation. Production of MDA-LM in the tissues was used as an indicator of lipid peroxidation. Production of MDA-LM was always enhanced by prior ischemia and reoxygenation. However, trauma also increased the production of MDA-LM both in nonischemic liver slices in vitro and in those subjected to ischemia and reoxygenation. Furthermore, the elimination of calcium from incubation buffer significantly reduced MDA-LM production both in nontraumatized, ischemic, and reoxygenated tissues and in traumatized, nonischemic tissues; while the addition of the calcium ionophore A23187 (10 mumol/L) increased MDA-LM production in nontraumatized tissues independently of ischemia and reoxygenation. In nonischemic, traumatized tissues, the iron chelators deferoxamine and CGP-46,700A (1,2-diethyl-3-hydroxypyrid-4-one) quenched MDA-LM production. These data indicate that either ischemia or mechanical trauma may predispose liver tissue to calcium-dependent and iron dependent oxidative stress. PMID- 8459456 TI - Piperacillin monotherapy compared with metronidazole and gentamicin combination in penetrating abdominal trauma. AB - The therapeutic efficacy and safety of piperacillin (4.5 g, every 6 hours) were compared with combined gentamicin (80 mg, every 8 hours) and metronidazole (500 mg every 6 hours) therapy in 246 patients hospitalized for penetrating abdominal injuries. Sixty-five patients had penetrating injury of the colon, rectum, or terminal ileum. The overall clinical cure rate was about 94% in both treatment groups. Adverse clinical experiences or biochemical abnormalities required discontinuation of therapy in three patients on gentamicin/metronidazole and in no patients on piperacillin. PMID- 8459457 TI - Epidural hematomas in the posterior cranial fossa. AB - A review of 89 cases of posterior fossa epidural hematoma (PFEDH) is presented. The mortality rate was 17.9%. In 44 cases (49.4%) there were associated intracranial hematomas. In 30 cases the hematoma was localized within the boundary of the foramen magnum and the transverse and sigmoid sinuses ("pure" PFEDH). In 59 cases the hematoma extended beyond the sinuses to the occipital area ("mixed" PFEDH). In the pure PFEDHs, the bleeder could be identified in only six cases and in five cases the source was a bleeding transverse sinus. The bleeders disclosed in the mixed PFEDHs were a torn transverse sinus in 28 cases, a meningeal artery in three cases, and a bony fracture in three cases. The possibility of a PFEDH should be kept in mind when evaluating patients who have suffered an occipital blow resulting in a frontal or temporal hematoma. In our series, patients with the pure PFEDHs with no associated intracranial hematomas had the best prognoses. Nine patients developed a PFEDH after surgery for a supratentorial hematoma. In 14 cases the PFEDH was treated at the subacute or chronic stage. All but one patient survived with a good recovery. Children generally had better prognoses. PMID- 8459458 TI - The role of secondary brain injury in determining outcome from severe head injury. AB - As triage and resuscitation protocols evolve, it is critical to determine the major extracranial variables influencing outcome in the setting of severe head injury. We prospectively studied the outcome from severe head injury (GCS score < or = 8) in 717 cases in the Traumatic Coma Data Bank. We investigated the impact on outcome of hypotension (SBP < 90 mm Hg) and hypoxia (Pao2 < or = 60 mm Hg or apnea or cyanosis in the field) as secondary brain insults, occurring from injury through resuscitation. Hypoxia and hypotension were independently associated with significant increases in morbidity and mortality from severe head injury. Hypotension was profoundly detrimental, occurring in 34.6% of these patients and associated with a 150% increase in mortality. The increased morbidity and mortality related to severe trauma to an extracranial organ system appeared primarily attributable to associated hypotension. Improvements in trauma care delivery over the past decade have not markedly altered the adverse influence of hypotension. Hypoxia and hypotension are common and detrimental secondary brain insults. Hypotension, particularly, is a major determinant of outcome from severe head injury. Resuscitation protocols for brain injured patients should assiduously avoid hypovolemic shock on an absolute basis. PMID- 8459459 TI - Ocular trauma among major trauma victims in a regional trauma center. AB - The authors conducted a retrospective review of the medical records of patients entering an adult level I regional trauma unit to ascertain descriptive epidemiologic information about ocular trauma occurring in the midst of major trauma. Over a 6-year period 6313 patients entered our trauma unit with major trauma. Of these, 856 (13.5%) patients had concomitant ocular trauma. Six hundred twenty-eight (73.4%) patients were male and 228 (22.6%) were female. The average age was 37 years with 743 (86.6%) victims aged between 15 and 55 years, 111 (13.0%) over the age of 55 years. Blacks constituted 48.8% of the sample with whites and other races accounting for 45.4% and 5.5%, respectively. Among the specific causes of ocular injury in our survey, motor vehicle crashes accounted for over 52% of the injuries. Assault-related ocular trauma was responsible for approximately 8% of these injuries. Nearly one third of patients had blood alcohol levels exceeding 100 mg/dL. The mean Revised Trauma Score and Injury Severity Score (based upon AIS-1985 severity coding) of the sample were 6.6 and 19.8, respectively. PMID- 8459460 TI - Nervous system injuries in horseback-riding accidents. AB - A review of 156 horseback-riding accidents that occurred in southern Alberta over a 6-year period and resulted in nervous system trauma, including 11 deaths, is presented. The majority (81%) of accidents occurred during recreational activity and 81% were associated with falling or being thrown from a horse. Head injury occurred in 92% of patients and accounted for all of the 11 deaths. Spinal injury occurred in 13% of the patients and was associated with head injury in 40%. One peripheral nerve injury was identified. Helmets were used by only two victims. The 11 deaths that occurred as a consequence of severe head injury accounted for 79% of all deaths associated with horseback riding. This profile of neurologic injuries associated with horse-related accidents supports a need for use of protective headgear. PMID- 8459461 TI - Delayed gastrointestinal reconstruction following massive abdominal trauma. AB - Routine use of the concepts of expeditious hemostasis including the use of packing and temporizing surgical resection without anastomosis followed by delayed reexploration and reconstruction in victims of major pancreaticoduodenal trauma encouraged us to manage other devastating abdominal injuries in a similar fashion. A variety of multiple organ injuries accompanied by massive blood loss, hypothermia, and acidosis also have been managed with the philosophy that hemostasis and control of continued gastrointestinal soiling were the only necessary initial surgical procedures. Following recovery room or surgical intensive care unit stabilization with full hemodynamic resuscitation and restoration of coagulation variables to normal, delayed definitive reconstruction was done. A summary of our experience and principles of management are presented. PMID- 8459462 TI - Selective use of pelvic roentgenograms in blunt trauma patients. AB - This study was initiated to investigate the need for routine pelvic roentgenograms for all blunt trauma victims. Over a 2-year period, we prospectively studied patients referred to the trauma service in the level I trauma center at our institution who met the inclusion criteria. The patients were evaluated by physical examination and, if mentally alert and reliable, were included in the study. After inclusion into the study, a routine pelvic roentgenogram was performed to substantiate the results of our physical examination. All 125 patients included in the study were found to have normal results on pelvic roentgenograms. We conclude that alert, oriented and reliable patients involved in blunt trauma do not need a routine pelvic roentgenogram if the findings on physical examination are negative. PMID- 8459463 TI - Unrecognized injuries in patients referred for emergency microsurgery. AB - Replantation of amputated parts and emergency microvascular repair of injured extremities are the two most common applications of clinical microsurgery. A major complication of emergency referral of such cases is the existence of the other injuries unrecognized at the time of initial evaluation. We have reviewed this complication within a series of emergency microsurgical cases referred to this unit. Several reports examining this problem of missed injuries exist in the general trauma literature. To our knowledge this study is the first to look at this important problem in the context of acutely injured patients referred for emergency microsurgery. A retrospective analysis of patients referred to Davies Medical Center over a 7-year period was performed. Nine of 1100 patients (0.8%) transferred to our unit for microsurgical evaluation and treatment had unrecognized coexisting injuries that put those patients at high risk for injury specific morbidity and demanded immediate changes in the original care planned at the time of referral. Brief case histories of these patients are outlined. We review the trauma literature of such injuries. A concise protocol elucidating the guidelines and pitfalls of emergency microsurgical referral is offered. PMID- 8459464 TI - Urgent paralysis and intubation of trauma patients: is it safe? AB - Physicians, fearful of an increase in the incidence of intubation mishaps (IMs) and pulmonary complications (PUCs), have been reluctant to use paralysis and intubation (PI) outside the OR. This study examines the correlations between PI, IM, and PUC. Since 1987, we have used PI when complex injury or combative behavior warranted. From January through December 1989, 851 patients meeting major trauma triage guidelines were evaluated. The medical records of 231 patients (27%) who underwent PI within 8 hours of admission were reviewed; 27 patients were eliminated because of incomplete records. The indications for PI were emergency surgery (131), airway control (30), combativeness (24), and hyperventilation (19). The location was the OR (121), ED (82), other (1). Presence or absence of IM was documented in 198 of 204 charts: Twenty-four IMs (12%) occurred--14 multiple attempts, seven aspirations, three esophageal intubations. Frequency of IM was not statistically related to PI location (Fisher's exact test), AIS, or ISS. In 194 of 204 patients who survived at least 24 hours, there were 15 PUCs (8%): eight pneumonia, five persistent infiltrates, two severe atelectases. No deaths were related to IM or PUC. There was no statistical relationship between IM and PUC (Fisher's exact test). However, patients with PUCs had a significantly higher AIS-chest score (2.9 +/- 1.7 vs. 0.9 +/- 1.5) (p < 0.0005, Student's t test) and ISS (27.3 +/- 9.6 vs. 14.5 +/- 10.8) (p < 0.0005, Student's t test). In our hands, PI is associated with low morbidity, no mortality, and can be safely used to facilitate injury management or to control combative behavior. PMID- 8459465 TI - The use of indirect calorimetry in critically ill patients--the relationship of measured energy expenditure to Injury Severity Score, Septic Severity Score, and APACHE II Score. AB - The nutritional needs of critically ill septic patients or patients with multiple injuries are often difficult to estimate. Indirect calorimetry can simply and accurately determine individual caloric and nutritional needs, especially in cases of critically ill patients with complicated injuries. This prospective study compared the measured energy expenditures of 30 patients using indirect calorimetry with their predicted basal energy expenditure according to the Harris Benedict equation, or their calculated energy expenditure derived from basal energy expenditure times, an activity factor, and a stress factor. These numbers were then used to evaluate the relationship between measured energy expenditure, measured energy expenditure per kilogram, and four specific scoring systems--the Septic Severity Score (SSS), the Injury Severity Score (ISS), the Trauma Score (TS), and APACHE II. The results showed the severity of sepsis or trauma correlated with the measured energy expenditure per kilogram of body weight. Among the 15 septic patients, in whom the measured energy expenditure per kilogram was 42.2 +/- 2.6 kcal/kg, the SSS provided a better predictor of energy needs and closer correlation with measured energy expenditure per kilogram (r = 0.69, Y = 1.41 + 0.72 X). Their stress factors could be modified as "0.97 + 0.0125 x SSS" to get a more accurate Harris-Benedict calculation. For the 15 patients with multiple injuries in whom the measured energy expenditure per kilogram was 34.9 +/- 1.6 kcal/kg, the ISS offered the best correlation with measured energy expenditure per kilogram (r = 0.84, Y = -31.47 +/- 1.73 X). Their stress factors could be modified as "1.04 + 0.0077 x ISS" to get a more accurate Harris-Benedict calculation. PMID- 8459466 TI - Impact of on-site care, prehospital time, and level of in-hospital care on survival in severely injured patients. AB - A sample of 360 severely injured patients was selected from a cohort of 8007 trauma victims followed prospectively from the time of injury to death or discharge. A case referent study was used to test the association between on-site care, total prehospital time, and level of care at the receiving hospital with short-term survival. Multiple logistic regression analyses showed that use of Advanced Life Support (ALS) at the scene was not associated with survival, whereas treatment at a level I compatible hospital was associated with a 38% reduction in the odds of dying, which approached statistical significance. Total prehospital time over 60 minutes was associated with a statistically significant adjusted relative odds of dying (OR = 3.0). The results of this study support the need for regionalization of trauma care and fail to show a benefit associated with ALS. PMID- 8459467 TI - A prospective study of blood loss with excisional therapy in pediatric burn patients. AB - Major blood loss occurs with excisional therapy of burns. To our knowledge no studies have quantitated blood loss in pediatric patients. This prospective study was performed to analyze blood loss in a pediatric burn population undergoing excision and grafting. Forty-four patients underwent 50 two-stage procedures. Blood loss was determined based on calculations of red cells administered in conjunction with estimates of total circulating red cell numbers. Results showed a mean value (+/- SEM) of 2.8% +/- 0.23% of circulating volume lost as a percentage of total body surface area (TBSA) excised, whereas 1.8% +/- 0.18% of circulating volume was lost as a percentage of TBSA grafted. Assessment of losses by age and depth of wound, patient age, and anatomic site showed no differences between these groups. Tourniquets lowered intraoperative losses but had no effect on overall losses. The value of knowing blood losses precisely is evaluated in terms of efficiency of ordering blood. PMID- 8459468 TI - Ultrasonography in blunt abdominal trauma: influence of the investigators' experience. AB - The validity of routine ultrasonography (US) in the evaluation of patients with blunt abdominal trauma (BAT) was investigated in a prospective study. From April 1989 to April 1990, 140 patients with suspected BAT were included in this study. Ultrasonography was performed by 17 surgeons using a standardized technique. The influence of the investigators' experience in US was manifested in the positive predictive value (PPV). Surgeons with a learning period of less than 1 year had a PPV of 60%. Investigators with experience of more than 1 year but less than 3 years had a PPV of 76%. For the most experienced investigators (> 3 years) a PPV of 92% was recorded. The sensitivity for intra-abdominal lesions was 100%, 100%, and 92%, and the specificity 94%, 89%, and 98% for the three levels of experience, respectively. We conclude that US is a suitable test for screening patients with BAT since it is highly sensitive, highly specific, complication free, and easy to learn. The positive findings of surgeons who are learning to use this method should be verified by reinvestigation by an experienced sonographer, by diagnostic peritoneal lavage (DPL), or by a CT scan if the patient is hemodynamically stable. PMID- 8459470 TI - Outcome of treatment of 686 gunshot wounds of the trunk at Los Angeles County-USC Medical Center: implications for the community. AB - The Los Angeles County-University of Southern California (LAC-USC) Medical Center, a level I trauma center, has experienced a rapidly increasing incidence of gunshot wounds (GSWs). We sought to enumerate the annual monetary costs and medical consequences of thoracoabdominal gunshot wounds in the epicenter of urban violence. A consecutive series of patients admitted from September 1, 1989 to August 31, 1990 was studied. Their records were coded by trauma nurse reviewers and held in the Trauma Emergency Medical Information System (TEMIS) and Automated Medical Record Abstracting and Reporting System (AMRARS). Diagnoses, procedures, and complications were verified by chart review. An estimate of disability 3 months after discharge was made from the record and reported on a functional activity scale. The total number of patients with GSWs admitted to all of the level I Los Angeles County trauma centers was 2771 during the study period. The total number of patients with major gunshot injuries admitted to LAC-USC Medical Center was 1007. Thoracoabdominal wounds without any head wound component occurred in 686 gunshot patients. Three quarters of the injured patients with truncal gunshot injuries were Hispanic. Total length of stay at the LAC-USC Medical Center for those with truncal wounds was 4666 hospital bed days including 432 ICU bed days, representing a minimum estimated total medical cost of $5,441,334. Annual medical cost of all admissions including rehabilitation, however, could be as great as $12 million for the Medical Center and $53 million for the County of Los Angeles. Thirty percent of patients had MediCal insurance. Payment could not be recovered from another 57% of patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8459469 TI - Medically related motor vehicle injury costs by body region and severity. AB - For motor vehicle crashes, we estimated the medically related costs of nonfatal injury by body region and severity. Our primary data sources were paid charges reported in the Detailed Claims Information data base of the National Council on Compensation Insurance and injury incidence and severity reported in the National Highway Traffic Safety Administration's National Accident Sampling System (NASS). Brain and lower extremity injuries account for the largest portion of medical costs. Spinal cord and severe brain injuries cost more per case. Our average costs per case are very close to those in a report to Congress but come from completely different data sources. Thus, national data bases are providing consistent medical cost estimates. PMID- 8459471 TI - Analysis of injuries following the crash of Avianca Flight 52. AB - Analyses of injuries sustained in airline disasters have been hampered by the frequent association of burn injury and by poor documentation. This report analyzes autopsy data from the crash of Avianca Flight 52 on Long Island, New York. There were 158 passengers of whom 73 died. The majority of persons had multiple organ injuries (average, 3.8/victim). Severe neurologic trauma included subarachnoid hemorrhage (65%), skull fracture (32%), and brain laceration (22%). Chest injuries included rib fractures (80%: average, 8.3/victim), hemothorax (58%), sternal fracture (22%), and lung contusion (33%). Orthopedic injuries (average, 4.4/victim) included pelvic (22%), tibial (37%), femur (22%), thoracic spine (33%), cervical spine (22%), and lumbar fractures (5%). Cardiovascular injuries included aortic transection (25%), heart laceration (14%), and major vascular injury (10%). Intra-abdominal injuries included liver (10%), spleen (8%), and kidney (10%). Unrestrained infants suffered severe injuries. Deaths in this airline disaster were from severe head and upper body injuries. This report may allow reappraisal of current restraint and safety measures. PMID- 8459472 TI - Cranial injury from unsuspected penetrating orbital trauma: a review of five cases. AB - Penetrating orbital-cranial injury is potentially life threatening. The history of the trauma and ophthalmologic examination may be misleadingly innocent; serious injury may be overlooked. We present five cases of orbital injury in which the diagnosis of intracranial extension was not obvious at the time of initial examination. A thorough history and physical examination should be performed on all patients, even those with apparently trivial injuries. Intracranial extension should be considered in any case where the injury was caused by an instrument small enough to enter the orbit. The threshold for obtaining a coronal CT scan of the orbits should be lowered, since this is the best way to detect an orbital roof fracture. PMID- 8459473 TI - Depressed skull fracture involving the superior sagittal sinus as a cause of persistent raised intracranial pressure: a case report. AB - A case of an open depressed fracture of the skull overlying and partially obliterating the superior sagittal sinus is reported. Depressed fractures overlying major venous sinuses as a cause of persistent elevated intracranial pressure (ICP) and poor neurologic outcome without treatment is discussed. Measurement of ICP and cerebral angiography may have a role to play in the management of these patients. PMID- 8459474 TI - Blunt abdominal aortic trauma in children: case report. AB - Injuries to the abdominal aorta as a result of blunt trauma in children are extremely rare. We encountered one such injury and a review of the literature revealed seven additional cases. Lower extremity ischemia, abdominal bruit, or paraplegia may suggest that diagnosis at the time of injury. Delayed presentations are characterized by abdominal pain or a pulsatile mass, with or without bruit. A high index of suspicion with early aortography is indicated to diagnose blunt aortic trauma. PMID- 8459475 TI - Traumatic aneurysm associated with fibrointimal proliferation of the common carotid artery following blunt trauma: case report. AB - Late neurologic symptoms following blunt trauma to the neck and upper torso were evaluated with duplex scanning of the carotid arteries and the diagnosis of a traumatic aneurysm of the common carotid artery with an associated stenosis was made. Resection and an end-to-end anastomosis resulted in an excellent outcome. Carotid aneurysm following blunt trauma is unusual and duplex scanning facilitated the diagnosis. Duplex scanning is useful in the evaluation of the carotid arteries in patients with posttraumatic neurologic symptoms. PMID- 8459476 TI - Traumatic intramyocardial dissection secondary to significant blunt chest trauma: a case report. AB - The case of a patient with delayed mitral regurgitation and right coronary artery traumatic injury in association with intramyocardial dissection without rupture or pseudoaneurysm is presented. These findings evolved secondary to blunt chest trauma and were confirmed by cardiac ultrasound scanning, magnetic resonance imaging, and cardiac catheterization. Successful surgical correction was facilitated with this combination of diagnostic testing. PMID- 8459477 TI - Traumatic subarachnoid-pleural fistula: case report and review of the literature. AB - Subarachnoid-pleural fistula is an unusual complication of spinal cord injury without radiologic abnormality (SCIWORA) and a rare cause of posttraumatic pleural effusion. The clinical presentation and surgical management of a child, the first with this complication seen at our institution, who sustained a T-6 SCIWORA and a cerebrospinal fluid-pleural effusion following a pedestrian-motor vehicle collision is discussed. Magnetic resonance imaging (MRI) proved superior to myelography in demonstrating the fistulous connection and associated cord damage. The fistula was successfully closed via a thoracotomy using a muscle and pleural plug. PMID- 8459478 TI - Traumatic paramediastinal air cyst: report of two cases and review of the literature. AB - Two cases of traumatic paramediastinal air cyst are presented with a review of the literature. This rare condition affects young people and usually occurs on the left side of the chest. Its course is spontaneously benign. Although they are usually easily diagnosed on chest roentgenograms, these cysts may sometimes be difficult to differentiate from other more serious traumatic lesions. Computed tomography (or a contrast swallow roentgenogram in some instances) can elucidate doubtful cases. PMID- 8459479 TI - Scapular and clavicular osteotomy for malunion: case report. AB - Fractures of the clavicle and scapula are usually treated conservatively. After malunion functional results are usually good, however, function and shoulder contour can be improved by corrective osteotomies. PMID- 8459480 TI - Combined Essex-Lopresti and radial shaft fractures: case report. AB - We present the case of a patient with multiple trauma, including a radial shaft fracture, a distal radioulnar joint dislocation, and a fracture-dislocation of the radial head. The combined open reduction of the radial shaft and head and the closed reduction of the distal radioulnar joint allowed early range of motion exercises and return to a functional level. PMID- 8459481 TI - Laparoscopically guided blood salvage and autotransfusion in splenic trauma: a case report. AB - Salvage of intraperitoneal blood with autotransfusion is a well-accepted practice. Laparoscopic examination is gaining popularity and holds diagnostic promise for the evaluation of trauma patients. We describe herein the successful combination of these techniques in a patient who sustained blunt abdominal trauma, facilitating splenic salvage, autotransfusion, and avoidance of laparotomy. PMID- 8459482 TI - Infection with Schistosoma mansoni in two different endemic areas: a comparative population-based study in Elziedab and Gezira-Managil irrigation schemes, Sudan. AB - A cross-sectional survey of schistosomiasis was carried out in five villages around the Elziedab irrigation scheme, in the north, and three villages in the Gezira-Managil area in central Sudan. Stools and urine from 53% (2832 individuals) and 72% (3684 individuals) of the population of these villages, respectively, were examined using the modified Kato thick smear for stools and sedimentation for urine. Clinical history and examination were done on 2832 subjects (53%) in Elziedab and on 893 (18%) randomly selected samples in Gezira Managil. Prevalence of Schistosoma mansoni was 36% in Elziedab and the mean egg count was 150 eggs per gram of faeces (e.p.g.). Prevalence of bloody diarrhoea was 6%, hepatomegaly 6% and splenomegaly 10%. There was a significant association between these parameters and infection in the age group 10-24 years. Prevalence and intensity in Gezira-Managil area were significantly higher than in Elziedab, 52% and 234 e.p.g. Prevalences of bloody stool 29%, hepatomegaly 17% and splenomegaly 15% were also significantly higher than in Elziedab. These parameters were unrelated to the presence of eggs in the stool. Advanced hepatosplenic schistosomiasis is less than 1% in both areas. While S. haematobium was not found in Elziedab, its prevalence varied from 10 to 15% in Gezira-Managil area. In conclusion, S. mansoni is much less prevalent in Elziedab than Gezira, signs and symptoms are much less prominent in Elziedab, and most of the symptoms are unrelated to the presence of eggs in the stool. PMID- 8459483 TI - Infectious diarrhoea in Hong Kong. AB - The role of enteric pathogens in diarrhoeal patients presenting at a large general hospital in Hong Kong from May 1984 to December 1990 was assessed. A total of 3267 organisms were isolated. The gastroenteric salmonellae were the most common pathogens (45%), followed by rotavirus (34%) and campylobacters (11%). Shigellae or vibrios constituted 5% or less of the total isolations. Both salmonellae and campylobacters were isolated more often from infants while rotavirus was more common in young children aged 1-4 years. Shigellae commonly affected young adults and vibrios mainly older patients. Rotavirus was most commonly isolated in the winter months while salmonellae and vibrios were more common in the hotter months. There was no seasonal predominance for shigellosis. Multiple infections occurred in 86 patients (3% of total cases); 42 of these patients had concurrent Salmonella and rotavirus infections and 22 had Campylobacter and rotavirus infections. Salmonellae remain a major public health problem in Hong Kong. PMID- 8459485 TI - Microfilaria prevalence of diurnally subperiodic Wuchereria bancrofti among people having a medical checkup in American Samoa in the past 17 years. AB - The yearly change of microfilaria (mf) prevalence rates from 1974 to 1990 was studied in American Samoa with people who had medical checkups. The mf rates were found to have been kept at a low level (0.8-2.6%) in the past 17 years. The continued low prevalence reduced clinical filariasis significantly in the past 8 years. The low level of endemicity, despite very close communication with neighbouring Western Samoa where filariasis is much more prevalent, could be explained by the urbanized living conditions in American Samoa. PMID- 8459484 TI - Prevalence of HIV infection and AIDS in Egypt over four years of surveillance (1986-1990). AB - Serosurveys were conducted from April 1986 to March 1990 to determine the prevalence of HIV-1 infections among Egyptians and foreigners. Sera from 29,261 high risk individuals and blood or blood product donors in Egypt, and from 10,326 foreigners were tested for HIV-1 antibodies by a recombinant HIV-1 and a recombinant combination HIV-1/HIV-2 enzyme immunoassay (EIA). Any serum found to be repeatedly reactive by EIA was tested by Western blot for confirmation of HIV 1 infection. The overall prevalence of HIV-1 infection among the Egyptians was 0.18% (54/29,261); of which 4.8% (28/582) were blood and factor VIII recipients, 0.15% (3/1961) drug addicts, 0.18% (3/1650) fever of unknown origin patients, 0.23% (6/2602) sexually transmitted disease patients, 1.9% (5/269) HIV-1 contacts, 0.07% (7/9778) international travellers, and 0.02% (2/12,070) blood/product donors. Evidence of HIV-1 infection was not demonstrated among 349 prostitutes. The prevalence of HIV-1 antibody among foreigners was 0.97% (100/10,326), who were mainly (94%) from other African countries. Among the total 54 HIV infected Egyptians, 20 developed AIDS, and at least 12 have died. Only one of the 100 infected foreigners was diagnosed with AIDS. While the number of AIDS cases has increased in Egypt over 18 months October 1988-March 1990, the overall prevalence of new HIV infections has decreased since 1988 and endemic transmission has not been documented in Egypt. PMID- 8459486 TI - Significance of Cryptosporidium as an aetiologic agent of acute diarrhoea in Calcutta: a hospital based study. AB - The significance of Cryptosporidium as a causative agent of acute diarrhoea has been assessed in a year long hospital based study. A significantly higher detection of Cryptosporidium (P < 0.01) was observed in cases as compared to controls. Cryptosporidium was detected alone from 3% of acute diarrhoeal patients and from 5.5% in combination with other enteric pathogens. However, only 1.1% of control subjects were positive for Cryptosporidium. The highest detection rate of Cryptosporidium oocysts was in the first two years of life, in both cases and controls. No sex specific predilection for Cryptosporidium was observed in either the cases or controls. PMID- 8459487 TI - Increasing risk of transfusion-associated AIDS as the pandemic spreads: experience in Maiduguri, Nigeria. AB - Complacency and financial considerations have led many hospitals in developing countries with low HIV antibody prevalence to disregard the importance of pre screening for HIV antibodies blood meant for transfusion. This report shows that during the year 1987 in which mandatory screening of donated blood was introduced at the University of Maiduguri Teaching Hospital, HIV antibody prevalence in donated blood units was 0%. However, four years later the prevalence had risen to 2.76%. This observation underlines the increasing risk to which transfusion recipients are exposed if given unscreened blood as HIV spreads with time. This spread can be rapid. PMID- 8459488 TI - Comparison of Vibrio cholerae serotype 01 strains isolated from patients and the aquatic environment. AB - Vibrio cholerae 01 strains of El Tor and Classical biotypes and Ogawa and Inaba serotypes were isolated from both patients and pond water, the latter used by the patients from whom the V. cholerae 01 strains had been isolated. Paired strains, i.e. from the patient and from the pond used by the patient, were compared. All strains were found to be non-hydrophobic and agglutinating in ammonium sulphate (2.0-2.5 M). They demonstrated similar antibiogram patterns and plasmids were not detected. Except for one clinical and one environmental strain, all strains caused fluid accumulation in the rabbit ileal loop (RIL). The outer membrane protein profiles of both clinical and environmental strains were nearly identical, except for the presence of an additional 22 kDa polypeptide, observed only in environmental strains. The protein profiles of two environmental isolates, analysed after passage through rabbits by oral feeding, were altered, demonstrating a significant decrease in the number of protein bands after animal passage but with the major protein band pattern remaining unchanged. Each passaged strain, however, demonstrated properties similar to the non-passaged culture in cell surface hydrophobicity, plasmid profile, antibiogram patterns, and enterotoxin production. PMID- 8459490 TI - Newfound genetic defect hints at clues for developing novel antimalarial agents. PMID- 8459491 TI - Tufts uses grant to design programs for drawing medical students into primary care careers. PMID- 8459493 TI - Air drop bundles average 9:1 food to medicine. PMID- 8459494 TI - From the Centers for Disease Control and Prevention. Influenza activity--United States and worldwide, and composition of the 1993-94 influenza vaccine. PMID- 8459489 TI - Interpersonal violence: patterns in a Basotho community. AB - This study was conducted to quantify the importance of trauma and death due to interpersonal violence in rural Lesotho and to gain an insight into the profile of the assault victims, the circumstances of the violent incidents and the type of weapons wielded and wounds inflicted. During a one-year period starting June 1988 information was recorded on all patients with assault trauma attending Quthing District Hospital. The annual incidence rate of assault on men between 20 and 49, the most affected age group, was estimated to be as high as 30 per 1000. The crude homicide rate could reliably be calculated as 44 per 100,000 per year. The male to female sex ratio amongst the 506 identified victims was 1.7:1. The assailants were male in 89% of the incidents; other men were their victim in 68% of these events. Only 26% of the consulting women suffered at the hands of their husband or partner. Over 55% of injuries (and deaths) inflicted by men were caused by beating with traditional sticks; 15% were due to stabbing. Women used stones, teeth or bare hands and feet equally frequently. The limited presence of firearms may have prevented higher death rates. It is suggested that the disruption of the social structure of the Basotho society through its dependence on migrant labour leads to weakened normative reference, the moral net, which is the underlying cause for the serious violence problem of the country. PMID- 8459492 TI - Tufts University Medical School Center explores genetic defenses of bacteria, cancer cells. PMID- 8459496 TI - From the Centers for Disease Control and Prevention. Update: dracunculiasis eradication--Ghana. PMID- 8459495 TI - From the Centers for Disease Control and Prevention. Inability of retroviral tests to identify persons with chronic fatigue syndrome, 1992. PMID- 8459499 TI - What are we teaching about indigent patients? PMID- 8459497 TI - What are we teaching about indigent patients? PMID- 8459498 TI - What are we teaching about indigent patients? PMID- 8459500 TI - What are we teaching about indigent patients? PMID- 8459501 TI - What are we teaching about indigent patients? PMID- 8459502 TI - What are we teaching about indigent patients? PMID- 8459503 TI - What are we teaching about indigent patients? PMID- 8459504 TI - What are we teaching about indigent patients? PMID- 8459505 TI - Breast cancer risk from diet, tobacco, and alcohol. PMID- 8459506 TI - Breast cancer risk from diet, tobacco, and alcohol. PMID- 8459508 TI - The resource-based relative value scale revisited. PMID- 8459507 TI - Breast cancer risk from diet, tobacco, and alcohol. PMID- 8459509 TI - Diagnosis of myocardial infarction by emergency department physicians. PMID- 8459510 TI - Investigation of potential HIV transmission to the patients of an HIV-infected surgeon. AB - OBJECTIVE: To ascertain if a surgeon infected with the human immunodeficiency virus (HIV) transmitted HIV to patients during invasive surgical procedures. DESIGN: Survey of patients and acquired immunodeficiency syndrome (AIDS) case registries, and laboratory analysis of nucleotide sequence data. SETTING: One surgeon's private and institutional practices within one academic referral hospital. PATIENTS: A total of 1131 persons identified in hospital databases who underwent invasive surgical procedures from 1984 through 1990 and for whom the surgeon was listed as the admitting or operating surgeon. MEASUREMENT: Patients presumed to be living were surveyed by mailed questionnaire. The AIDS case registries were reviewed for all patients having undergone invasive procedures and death certificates were obtained. Person-hours of surgery during which exposure might have occurred were calculated for surgical procedures. RESULTS: Of 1131 patients, 101 were dead, 119 had no address, 413 had test results known, and 498 did not respond to the questionnaire. No study patient name was found in reported AIDS case registries. One newly detected, HIV-seropositive patient was determined (through nucleotide sequencing) to have been most probably infected in 1985 during a transfusion. There was no HIV transmission in 369 person-hours of surgical exposure, indicating that HIV transmission to patients is unlikely to occur more frequently than once per 1000 person-hours of surgical exposure. CONCLUSIONS: If study validity and resources permit, investigation of publicly disclosed, HIV-infected health care workers whose practices involve invasive procedures should be pursued. The risk of HIV transmission during surgery may be so small that it will be quantified only by pooling data from multiple, methodologically similar investigations. PMID- 8459511 TI - Absence of HIV transmission from an infected dentist to his patients. An epidemiologic and DNA sequence analysis. AB - OBJECTIVE: To determine if a general dentist with human immunodeficiency virus (HIV) infection transmitted HIV to any of his patients. DESIGN: A cohort study in which all patients treated by a dentist who developed the acquired immunodeficiency syndrome (AIDS) were identified and attempts were made to contact all patients for HIV antibody testing. SETTING: A general dentistry clinic operated by the Department of Veterans Affairs in southeastern Florida. PARTICIPANTS: All patients treated by a dentist during the 5 3/4 years before he developed AIDS were identified in a computerized registry of dental care. MAIN OUTCOME MEASURES: Attempts were made to contact all living patients for counseling and HIV antibody testing. Living patients with newly identified HIV infection were interviewed, and DNA sequence analysis was performed to compare genetic relatedness of their HIV to that of the dentist. Death certificates were obtained for decreased patients, and the medical records of those with diagnoses suggestive of HIV disease or drug abuse and those dying under the age of 50 years were reviewed in detail. RESULTS: There were 1192 patients who had undergone 9267 procedures, of whom 124 were deceased. A review of the death certificates of the deceased patients identified five who had died with HIV infection, all of whom were either homosexuals or users of illicit intravenous drugs. We were able to locate 962 (92%) of the remaining 1048 patients, and 900 agreed to be tested. Infection with HIV was documented in five of the 900 patients, including four who had clear evidence of risk factors for acquiring HIV infection. One patient who had only a single evaluation by the dentist denied high-risk behavior. Comparative DNA sequence analysis demonstrated that the viruses from the dentist and these five patients were not closely related. CONCLUSION: This study indicates that the risk for transmission of HIV from a general dentist to his patients is minimal in a setting in which universal precautions are strictly observed. Programs to ensure compliance with universal precautions would appear preferable to programs for widespread testing of dentists. PMID- 8459513 TI - The overdiagnosis of Lyme disease. AB - OBJECTIVE: To analyze the diagnoses, serological test results, and treatment results of the patients evaluated in a Lyme disease clinic, both prior to referral and from current evaluation. DESIGN: Retrospective case survey of prescreened patients. SETTING: Research and diagnostic Lyme disease clinic in a university hospital. PATIENTS: All 788 patients referred to the clinic during a 4.5-year period who were thought by the referring physician or the patient to have a diagnosis of Lyme disease. MAIN OUTCOME MEASUREMENTS: Symptoms and signs of disease, immunodiagnostic tests of Lyme disease, and tests of neurological function. RESULTS: Of the 788 patients, 180 (23%) had active Lyme disease, usually arthritis, encephalopathy, or polyneuropathy. One hundred fifty-six patients (20%) had previous Lyme disease and another current illness, most commonly chronic fatigue syndrome or fibromyalgia; and in 49 patients, these symptoms began soon after objective manifestations of Lyme disease. The remaining 452 patients (57%) did not have Lyme disease. The majority of these patients also had the chronic fatigue syndrome or fibromyalgia; the others usually had rheumatic or neurological diseases. Of the patients who did not have Lyme disease, 45% had had positive serological test results for Lyme disease in other laboratories, but all were seronegative in our laboratory. Prior to referral, 409 of the 788 patients had been treated with antibiotic therapy. In 322 (79%) of these patients, the reason for lack of response was incorrect diagnosis. CONCLUSIONS: Only a minority of the patients referred to the clinic met diagnostic criteria for Lyme disease. The most common reason for lack of response to antibiotic therapy was misdiagnosis. PMID- 8459514 TI - Standards for pediatric immunization practices. Ad Hoc Working Group for the Development of Standards for Pediatric Immunization Practices. PMID- 8459512 TI - Absence of HIV transmission from an infected orthopedic surgeon. A 13-year look back study. AB - OBJECTIVE: To determine the risk of human immunodeficiency virus (HIV) transmission from an HIV-infected orthopedic surgeon to patients undergoing invasive procedures. DESIGN: Retrospective epidemiologic follow-up study. PARTICIPANTS: A total of 2317 former patients on whom the orthopedic surgeon performed invasive procedures between January 1, 1978, and June 30, 1991 [corrected]. MAIN OUTCOME MEASURES: HIV infection or death from an acquired immunodeficiency syndrome (AIDS)-defining tumor or opportunistic infection. RESULTS: An orthopedic surgeon voluntarily withdrew from practice after testing positive for HIV. Testing for HIV was performed on 1174 former patients, representing 50.7% of patients on whom the orthopedic surgeon performed invasive procedures during the 13.5-year period. Patients were tested from each year and from each category of invasive procedure. All patients were HIV-negative by enzyme-linked immunosorbent assay. Two former patients reported known HIV infection prior to surgery. Review of AIDS case registries and vital records failed to detect cases of HIV infection among former surgical patients. The estimated cost of the initial patient notification and testing was $158,500. The patient notification and testing were conducted while maintaining the confidentiality of the orthopedic surgeon who was an active participant in the planning and execution of the study. CONCLUSIONS: The risk of HIV transmission from an HIV-infected surgeon who adheres to recommended infection control practices is extremely low. Notification and HIV testing of former patients in this setting is both disruptive and expensive and is not routinely recommended. PMID- 8459515 TI - Clinical manifestations and treatment of dysfunctional uterine bleeding. AB - Dysfunctional uterine bleeding is a common gynecologic disorder that can affect any woman during her reproductive years. It is a diagnosis of exclusion, and the clinician must proceed through a logical stepwise evaluation to rule out all other causes of the abnormal bleeding. In most cases dysfunctional uterine bleeding is associated with anovulation. During the pubertal and perimenopausal periods, anovulatory bleeding is a common occurrence. During these transitional states, the abnormal bleeding has a physiological basis and is secondary to an estrogen withdrawal. Anovulatory bleeding can also be associated with chronic anovulation. The chronic unopposed estrogen that characterizes this disorder causes a continuous proliferation of the endometrium; this can result in abnormal bleeding and place the patient at risk for endometrial cancer. The goals of treatment for anovulatory bleeding are to stop the acute bleeding, avert future episodes, and prevent long-term complications. In some cases surgical intervention is indicated, but the foundation of treatment has been a medical approach. Several progestational agents have demonstrated effectiveness and can be administered either orally or by intramuscular injection. If the patient fails to have resolution of the bleeding with medical therapy, another cause of the bleeding must be suspected, and reevaluation is necessary. PMID- 8459517 TI - Shingles. Sorrows, salves, and solutions. PMID- 8459516 TI - Anticytokine strategies in the treatment of the systemic inflammatory response syndrome. AB - The systemic inflammatory response syndrome (SIRS) is an acute illness characterized by generalized activation of the endothelium. The most severe form of the syndrome is found in patients with shock due to gram-negative sepsis. We examined both animal and limited human data for the contribution of cytokines to this syndrome. Cytokines are endogenously produced proteins of small molecular weight and multiple biological effects. The cytokines interleukin 1 (IL-1) and tumor necrosis factor (TNF), as well as interferon-gamma and interleukin 8, are discussed. Laboratory investigations suggest that these cytokines play a critical role in SIRS by promoting the biochemical and clinical characteristics of SIRS. The biochemical changes induced by TNF and IL-1 include increased synthesis of nitric oxide, prostaglandins, platelet-activating factor, and endothelial cell adhesion molecules. Specific blockade of TNF using neutralizing antibodies or soluble receptors to TNF in animal models of SIRS reduces mortality and severity of disease. Similar results have been observed blocking IL-1 using soluble IL-1 receptors or IL-1 receptor antagonists. Preliminary clinical studies suggest that blockade may be useful in treating human SIRS. The various strategies for blocking IL-1 and TNF are presented; in addition, their mechanism(s) of action and safety in humans are discussed. We conclude that based on animal studies and preliminary clinical trials, strategies to block IL-1 or TNF may benefit patients with the syndrome, although thorough clinical trials have not been completed. PMID- 8459518 TI - Confronting multidrug resistance. A role for each of us. PMID- 8459519 TI - HIV-infected surgeons and dentists. Looking back and looking forward. PMID- 8459520 TI - Giving pediatric immunizations the priority they deserve. PMID- 8459521 TI - Reflections on a century of excellence. PMID- 8459522 TI - A piece of my mind. Painful lessons. PMID- 8459523 TI - [Epidemiology of glaucoma]. PMID- 8459524 TI - [Cataract]. PMID- 8459525 TI - [Idiopathic hypoparathyroidism and pseudohypoparathyroidism]. PMID- 8459526 TI - [Malignant ophthalmic tumors]. PMID- 8459527 TI - [Amyloidosis]. PMID- 8459529 TI - [Weber-Christian disease]. PMID- 8459528 TI - [Malignant hyperthermia]. PMID- 8459530 TI - [Lactate dehydrogenase subunits deficiencies]. PMID- 8459531 TI - [Hereditary disease with hyper-sensitivity to radiation]. PMID- 8459532 TI - [Adenine phosphoribosyltransferase deficiency]. PMID- 8459533 TI - [Lymphoedema]. PMID- 8459534 TI - [Statistical survey of hypopituitarism in Japan]. PMID- 8459536 TI - [Chronic fatigue syndrome]. PMID- 8459535 TI - [Hand-Schueller-Christian disease and eosinophilic granuloma]. PMID- 8459537 TI - [Measures against intractable diseases in Japan]. PMID- 8459538 TI - [Cushing's syndrome]. PMID- 8459539 TI - [Primary aldosteronism]. PMID- 8459540 TI - [Clinical characteristics of Japanese patients with congenital adrenal hyperplasia]. PMID- 8459541 TI - [Pheochromocytoma]. PMID- 8459542 TI - [Polycystic ovary syndrome]. PMID- 8459543 TI - [Sexual precocity]. PMID- 8459544 TI - [Sexual impotence]. PMID- 8459545 TI - [Insulinoma--a statistical review of 443 cases in Japan]. PMID- 8459546 TI - [Carcinoids and the carcinoid syndrome]. PMID- 8459547 TI - [Statistical survey of pituitary dwarfism in Japan]. PMID- 8459548 TI - [Tumor with ectopic ADH production]. PMID- 8459549 TI - [Ectopic hormone-producing tumor]. PMID- 8459550 TI - [Epidemiology of obesity]. PMID- 8459551 TI - [Statistical survey of acromegaly in Japan]. PMID- 8459552 TI - [Diabetes mellitus--epidemiologic and clinical statistics in Japan]. PMID- 8459553 TI - [Functional abnormalities of insulin receptor]. PMID- 8459554 TI - [Hypoglycemia]. PMID- 8459555 TI - [Glycogen storage disease]. PMID- 8459556 TI - [Hyperlipidemia]. PMID- 8459557 TI - [Statistical survey of anorexia nervosa in Japan]. PMID- 8459558 TI - [Hypolipidemia]. PMID- 8459559 TI - [Lipidosis]. PMID- 8459560 TI - [Statistical survey of prolactin producing tumor in Japan]. PMID- 8459561 TI - [Disorders of amino acids]. PMID- 8459562 TI - [Hyperuricemia]. PMID- 8459563 TI - [Porphyrias]. PMID- 8459564 TI - [Osteoporosis]. PMID- 8459565 TI - [Acute glomerulonephritis]. PMID- 8459566 TI - [Chronic glomerulonephritis]. PMID- 8459567 TI - [Changing patterns of acute renal failure--from clinical statistics]. PMID- 8459568 TI - [Empty sella syndrome]. PMID- 8459569 TI - [Chronic renal failure]. PMID- 8459570 TI - [Clinical and epidemiological data of nephrotic syndrome in Japan]. PMID- 8459571 TI - [Interstitial nephritis and pyelonephritis]. PMID- 8459572 TI - [Drug-induced nephropathy]. PMID- 8459573 TI - [Autosomal dominant polycystic kidney diseases]. PMID- 8459574 TI - [Renovascular hypertension]. PMID- 8459575 TI - [Statistic survey of diabetes, insipidus, nephrogenic diabetes insipidus in Japan]. PMID- 8459576 TI - [Urolithiasis]. PMID- 8459577 TI - [Anomalies of the upper urinary tract]. PMID- 8459578 TI - [Urologic aspects of sexually transmitted diseases]. PMID- 8459579 TI - [Urinary tract infection]. PMID- 8459580 TI - [Rheumatic fever]. PMID- 8459581 TI - [Rheumatoid arthritis]. PMID- 8459582 TI - [Systemic lupus erythematosus (SLE)]. PMID- 8459583 TI - [Systemic scleroderma]. PMID- 8459584 TI - [Graves' disease]. PMID- 8459585 TI - [Dermatomyositis and polymyositis]. PMID- 8459587 TI - [Temporal arteritis]. PMID- 8459588 TI - [Wegener's granulomatosis]. PMID- 8459589 TI - [Sweet's syndrome]. PMID- 8459590 TI - [Sjogren's syndrome]. PMID- 8459586 TI - [Mixed connective tissue disease]. PMID- 8459591 TI - [Allergic granulomatous angiitis]. PMID- 8459592 TI - [Plummer's disease]. PMID- 8459593 TI - [Behcet's disease]. PMID- 8459594 TI - [Primary immunodeficiency diseases]. PMID- 8459595 TI - [Secondary immunodeficiency diseases]. PMID- 8459596 TI - [Drug allergy]. PMID- 8459597 TI - [Acquired immunodeficiency syndrome (AIDS)]. PMID- 8459598 TI - [Subacute thyroiditis]. PMID- 8459599 TI - [Brain tumor]. PMID- 8459600 TI - [Thyroid cancer]. PMID- 8459601 TI - [Statistical review of esophageal cancer in Japan]. PMID- 8459602 TI - [Statistical review of lung cancer]. PMID- 8459603 TI - [Statistical review of mediastinal tumors]. PMID- 8459604 TI - [Chronic thyroiditis]. PMID- 8459605 TI - [Pleural mesothelioma]. PMID- 8459606 TI - [Statistical review of carcinoma of the breast]. PMID- 8459607 TI - [Gastric cancer--a comprehensive review on epidemiological and clinical data and results of treatments in Japan]. PMID- 8459608 TI - [Statistical review of primary liver cancer]. PMID- 8459609 TI - [Statistical review of biliary tract cancer]. PMID- 8459610 TI - [Statistic review of pancreatic carcinoma]. PMID- 8459611 TI - [Statistical review of cancer of the intestines]. PMID- 8459612 TI - [Statistical review of adrenal cortical carcinoma]. PMID- 8459613 TI - [Hypothyroidism]. PMID- 8459614 TI - [Statistical review of renal carcinoma]. PMID- 8459615 TI - [Cervical cancer]. PMID- 8459616 TI - [Statistical review of ovarian tumor]. PMID- 8459617 TI - [Statistical review of prostatic cancer]. PMID- 8459618 TI - [Clinical statistical studies of bladder cancer in Japan]. PMID- 8459619 TI - [Thyroid hormone resistance]. PMID- 8459620 TI - [Statistical review of testicular tumor]. PMID- 8459621 TI - [Statistical review of bone tumors]. PMID- 8459623 TI - [Viral hemorrhagic fevers]. PMID- 8459622 TI - [Statistical review of Malignant melanoma and its precancerous condition]. PMID- 8459624 TI - [Parasitic infections]. PMID- 8459625 TI - [MRSA infection]. PMID- 8459626 TI - [Infection due to gram negative rod]. PMID- 8459627 TI - [Legal infectious diseases]. PMID- 8459628 TI - [Primary hyperparathyroidism]. PMID- 8459629 TI - [Ossification of the spinal ligament]. PMID- 8459630 TI - [Idiopathic osteonecrosis of the femoral head]. PMID- 8459631 TI - [Ankylosing spondylitis]. PMID- 8459632 TI - [Meniere's disease and its related diseases]. PMID- 8459633 TI - [Hearing loss]. PMID- 8459634 TI - [Epidermolysis bullosa and pemphigus]. PMID- 8459635 TI - [Pustular psoriasis and psoriasis vulgaris]. PMID- 8459636 TI - [Phacomatosis]. PMID- 8459637 TI - [Chorioretinal dystrophies]. PMID- 8459638 TI - Exogenous hormones and human cancer. AB - The importance of the role of endogenous hormones in carcinogenesis of the breast, endometrium, ovary and testis is well known. Exogenous hormones have become an important issue in human carcinogenesis because the number of case reports suggesting its relation to iatrogenic hormone usage is increasing due to the increased hormone consumption from various medical treatments. The risk of adenoma and carcinoma of the liver and endometrium caused by oral contraceptives has been clarified after relatively long-term experience. We have reviewed the risk from exogenous hormones, such as oral contraceptives, supplemented estrogens, tamoxifen, synthetic anabolic steroids, including danazol, clomiphene and growth hormone, and other growth factors produced by genetic engineering because of their possible role in causing human neoplasms. PMID- 8459639 TI - Bronchoscopic ultrasonography in the diagnosis of lung cancer. AB - An ultrasonic bronchoscope has been newly developed for diagnosis and lymph node staging in the hilum and mediastium. The instrument comprises an Echo-camera, SSD 630 (Aloka), and a transbronchial ultrasonic probe similar to the currently used videobronchoscope. The scope is equipped with an ultrasonic transducer in its tip. The maximum diameter of the probe head is 6.3 mm and that of the transducer, 5.0 mm. The frequency employed is 7.5 Megahertz (MHz) and the direction of scanning is parallel to the bronchoscopic axis. The device can easily be introduced into the lobar bronchus under topical anesthesia in a similar procedure to that used for routine videobronchoscopy. The location of the transducer in the airway is confirmed by monitoring endoscopic images on a TV monitor screen. With the device, 25 patients, who had given their consent for the ultrasonographic study beforehand, were examined during the two-month period, January and February, 1992. Vessels such as the thoracic aorta, pulmonary artery and truncus brachiocephalicus were good landmarks for diagnosis. Lung cancer was detected in five patients by biopsy, three malignant lesions in the hilum were diagnosed by videobronchoscopy while two malignant lesions in the periphery were confirmed by bronchoscopic ultrasonography as anterior mediastinal lymph node swellings. PMID- 8459640 TI - Antitumor effect and survival benefit of chemotherapy for unresectable advanced gastric cancer. AB - The "Criteria for Evaluating the Efficacy of Chemotherapy/Radiation Therapy in the Treatment of Gastric Cancer" are now widely used in Japan. To assess the validity of the criteria, the relation between the antitumor effect evaluated by the criteria and the survival of patients with gastric cancer was analyzed. The subjects were 169 patients with unresectable advanced gastric cancer who were entered into a randomized comparative trial of tegafur plus mitomycin C, or UFT (a combination of uracil and tegafur in a 4:1 molar ratio) plus mitomycin C. Irrespective of their performance status, disease extent and chemotherapy regimen, responding patients showed improved survival over non-responding patients. If the primary gastric lesion responded to chemotherapy, prolongation of survival was noted in patients with a measurable gastric lesion as well as in those with a non-measurable but evaluable gastric lesion. No improvement in survival was recognized among patients having a primary gastric lesion which did not respond to chemotherapy, even if the metastases showed a response. The results obtained in the present study indicate the validity of the criteria, except for diffusely infiltrating gastric lesions. PMID- 8459642 TI - Prophylactic lymphadenectomy vs observation vs inguinal biopsy in node-negative patients with invasive carcinoma of the penis. AB - From 1962 to 1984, 423 patients with invasive penile cancer and negative groin nodes were subjected to prophylactic lymphadenectomies (n113), observations (n258) or inguinal biopsies (n52) in a non-randomised fashion. The numbers of patients with T2, T3 and T4 lesions were similar in the three groups. The overall five-year disease-free survivals were 94, 93 and 85%, respectively. All groin recurrences in the observation group occurred within 18 months of the surgery for the primary tumor. The five-year disease-free survivals of node-positive patients in the lymphadenectomy and observation groups were 100 and 76%, respectively; three patients in the latter group had refused surgical treatment when their adenopathy was mobile. Morbidity from the prophylactic lymphadenectomies included wound breakdown in 61%, wound infection in 18% and lymphedema in 25% of patients. We feel that neither prophylactic lymphadenectomy nor inguinal biopsy are justified in these patients. Close observation of the groin nodal status would be appropriate. PMID- 8459641 TI - Hemorrhagic cystitis associated with allogeneic and autologous bone marrow transplantation for malignant neoplasms in adults. AB - We investigated the occurrence of hemorrhagic cystitis in 30 consecutive adult patients undergoing bone marrow transplantation (BMT) for hematological and non hematological malignancies. Ten patients with hematological malignancies received allogeneic BMT, and twenty patients, seven with hematological and 13 with non hematological malignancies, received autologous BMT. All 30 patients received high-dose cyclophosphamide-containing regimens (120 mg/kg in 16, 200 mg/kg in one, 6000 mg/m2 in 13) as preparative therapies. They all received 2 mercaptoethane sulphonate sodium (mesna) combined with hyperhydration 3 liter/day as prophylaxis for hemorrhagic cystitis. Bladder irrigation was not performed. Overall, five patients (16.7%) developed hemorrhagic cystitis; early-onset (within 48 hours of the end of the high dose chemoradiotherapy) hemorrhagic cystitis occurred in one (3.3%; 95% confidence interval, 0.6-16.7%) and late onset occurred in four (13.3%; 95% confidence interval, 5.3-29.7%). In three of the four late-onset cases, adenovirus was isolated from the urine specimens at the onset of the hemorrhagic cystitis. Among the 13 patients with non hematological malignancies receiving autologous BMT, one with recurrent breast cancer developed late-onset hemorrhagic cystitis associated with adenovirus type 11. We conclude the prophylactic measure with mesna and hyperhydration to be effective enough to prevent cyclophosphamide-induced hemorrhagic cystitis of early onset. Some BMT recipients, however, even those with non-hematological malignancies undergoing autologous BMT, develop late-onset hemorrhagic cystitis in which adenovirus is considered a principal causative agent. PMID- 8459643 TI - Primary adenocarcinoma arising in the jejunal limb of a Roux-en-Y esophagojejunostomy: a case report. AB - Adenocarcinoma of the small bowel is uncommon. Due to the paucity and lack of specificity of symptoms, patients are usually seen late in the course of their illness when curative therapy, mainly represented by wide surgical resection, is unlikely. The authors report a case of primary adenocarcinoma arising in the jejunal limb transposed for a Roux-en-Y esophagojejunostomy reconstruction eight years after a total gastrectomy performed for an advanced gastric cancer (pT2N1M0), with mixed histological pattern (tubular-mucinous) and negative CEA staining of cancer cells. Evidence for excluding the possibility of a recurrence of the primitive gastric cancer was based on the different histologic pattern, positive CEA staining of cancer cells and other features of the second neoplasm. Early diagnosis of the neoplasm was made possible by its favorable anatomic location and the early onset of symptoms, which prompted effective surgical therapy (wide resection). The authors, furthermore, analyze and discuss the possible pathogenesis of the neoplasm, based on the evidence of slow jejunal limb emptying, elevated concentration of N-Nitroso compounds and contamination by N nitrosating bacteria in the jejunal limb juice, suggesting that each of these factors could have had a role to play in the development of the jejunal malignancy. PMID- 8459644 TI - Ossifying fibromyxoid tumor of soft parts: a case report. AB - A case of ossifying fibromyxoid tumor of soft tissue parts in the presacral region, which developed in a 46-year-old Japanese man is reported. The enucleated tumor was an encapsulated, elastic, hard mass measuring 2.5 x 2.2 x 1.4 cm. Microscopically, the tumor was characterized by foci of round to polygonal cells dispersed in a fibromyxoid matrix, containing varying amounts of collagen and osteoid tissue. At the marginal zone, the shell of bone and osteoid tissue with calcification separated the tumor from the surrounding tissues. Our patient is showing no evidence of recurrence after a one-year follow-up period. The findings are compatible with those proposed for ossifying fibromyxoid tumor of soft parts by Enzinger et al. in 1989. This tumor should be differentiated from cartilaginous, osteogenic and neural tumors. PMID- 8459645 TI - Dacron fabric-enveloped alumina ceramic prosthesis for cementless resection arthroplasty of the proximal tibia: a case report with a long-term result. AB - After resection of the primary lesion, the right proximal tibia of a patient with osteosarcoma was reconstructed using a Dacron fabric-enveloped alumina ceramic total knee prosthesis without cement. Dacron fabric is intended to act as a scaffold upon which connective tissue can proliferate and form new ligament and other supporting soft tissues. Usually, following wide resection of the primary lesion, the supporting system is lost. If the supporting soft tissues are not reconstructed after removal of the tumor, they will be fixed in a slackened condition and will not provide sufficient support, leading to problems of stability and function. Using alumina ceramics alone does not induce surrounding connective tissue formation; therefore, stability is not ensured. The support of the vascular tissue enables the fabric to carry out the functions of ligaments, tendons, retinaculum, periosteum, joint capsule and other supporting soft tissues. Over time, stabilization occurs, biologic fixation of the prosthesis to the supporting soft tissues is successful and the durability of the prosthesis is prolonged. Postoperative follow-up has continued for a 77-month period. At present, the patient continues to show no evidence of disease and is able to walk painlessly up and down stairs without using a knee brace or handrail. A knee brace was recommended, however, to ensure the durability of the prosthesis. Dacron fabric is useful for the repair of supporting soft tissues without significant complications. Using this unique method, a stable, functional and aesthetically pleasing reconstruction can be accomplished. PMID- 8459646 TI - Primary malignant melanoma of the female urethra: a case report. AB - A case of primary malignant melanoma of the female urethra is presented. A 65 year-old Japanese woman was referred with dysuria and urethral bleeding. A hemorrhagic blue-black tumor, 3 cm in diameter, was diagnosed as a malignant melanoma by urinary cytology and biopsy. In spite of radical surgery followed by adjuvant immunochemotherapy with beta interferon, dacarbazine, nimustine and vincristine (IFN beta-DAV), the patient died of the disease one year after surgery because of lung metastasis which developed six months after diagnosis. The regional lymph nodes were not involved. In the present paper, we have briefly discussed the diagnostic value of cytological examination for this condition, as well as biopsy, with regard to the risk of hematogeneous tumor spread. PMID- 8459647 TI - A simple chemiluminescence method for measuring oxygen-derived free radicals generated in oxygenated rat myocardium. AB - We have developed a simple and reproducible method employing chemiluminescence to measure oxygen-derived free radicals generated in oxygenated myocardium. Isolated perfused rat hearts were frozen in liquid nitrogen during the control perfusion (non-ischemia), after 30 min of global ischemia (ischemia), or after 20 min of reperfusion following 30-min global ischemia (reperfusion). The frozen hearts were ground to a fine powder and then oxygenated by mixing with phosphate buffered saline (PBS) (pH 7.4 and PO2 183-194 mmHg) containing lucigenin. The mixed solution was injected into a chemiluminescence detection flow cell. The chemiluminescence intensity increased in relation to the lucigenin and myocardium contents of the test solution. However, it was not affected by the temperature of PBS in the range of 25 degrees C to 50 degrees C. The chemiluminescence intensity of ischemic myocardium was 2.5 times larger than that of non-ischemic or reperfused myocardium (P < 0.01). Recombinant human superoxide dismutase (r-h SOD) reduced dose-dependently the chemiluminescence intensity induced by oxygenation of ischemic myocardium, while chemically inactivated r-h-SOD did not. PMID- 8459648 TI - Enhanced production of platelet-activating factor in stimulated rat leukocytes caused by the blockade of lysophospholipid acylation. AB - We have previously reported that triacsin C, an acyl-CoA synthetase inhibitor, enhanced the production of platelet-activating factor (PAF) in calcium ionophore activated rat polymorphonuclear leukocytes (PMNs). In this report, we further demonstrated that the production of PAF by PMNs in response to opsonized zymosan was significantly enhanced by pretreatment with triacsin C and also by the pretreatment with merthiolate, which was reported to be an inhibitor of acyl CoA/lysolecithin acyltransferase. Pretreatment with triacsin C or merthiolate also enhanced the lyso-PAF content in the stimulated PMNs. Addition of lyso-PAF in the incubation mixture of PMNs in the presence of opsonized zymosan augmented the production of PAF. The enhancement of PAF production by lyso-PAF has been reported by several authors, and the importance of lyso-PAF in the remodeling pathway of PAF synthesis has been generally recognized. Therefore, from the above findings, it is assumed that blockades of the reacylation of lyso-phospholipids, by inhibitors such as triacsin C and merthiolate, might lead to accumulation of lyso-PAF and might result in the enhancement of PAF production when the remodeling pathway is active. PMID- 8459649 TI - Mechanism by which indomethacin delays gastric ulcer healing in the rat: inhibited contraction of the ulcer base. AB - Repeated administration of indomethacin delays the healing of acetic acid-induced gastric ulcers in rats, but the underlying mechanism remains unclear. We examined the effect of indomethacin on the contraction of the connective tissue isolated from the base of 1-week-old ulcers. The tissue samples, suspended in an organ bath, were contracted by serotonin, bradykinin and carbachol and also slightly contracted by prostaglandin (PG) F1 alpha. The effect of serotonin was the most potent. However, 6-keto-PGF1 alpha, PGE2 and histamine had little or no contraction inducing effect. The contractile response to serotonin of the tissue in the indomethacin-treated group was significantly less than that in the control group (without indomethacin treatment). After a 2-week treatment with indomethacin, a histological study of the ulcers showed that the length of rupturing of the muscularis mucosa was significantly greater than that observed in the control group. However, indomethacin had no effect on the length of the regenerated mucosa and the thickness of the ulcer base. We conclude that the connective tissue at the ulcer base has the ability to contract and that the prevention of the contraction of the tissue by indomethacin might be involved in the mechanism underlying delayed ulcer healing. PMID- 8459650 TI - Effects of indomethacin and prednisolone on the different stages of healing of acetic acid-induced gastric ulcers in the rat. AB - Repeated administration of indomethacin or prednisolone for 2 weeks apparently delayed the healing of initial gastric ulcers induced by acetic acid injection in rats. While indomethacin significantly interfered with the healing of partially healed 2-week-old ulcers, prednisolone did not. Indomethacin had no effect on the healing of "unhealed" 4-week-old ulcers. However, prednisolone significantly enhanced the healing of such "unhealed" ulcers, and it decreased the weight of the connective tissue at the ulcer base and the collagen content. These results suggest that prednisolone enhances the healing of "unhealed" gastric ulcers by degrading the fibroplasia that had amply developed in the connective tissue. PMID- 8459651 TI - Effects of nerve growth factor (NGF) in rats with basal forebrain lesions. AB - Effects of nerve growth factor (NGF) on the basal forebrain (BF) lesion-induced amnesia in rats were investigated. When NGF infusion was begun immediately after the formation of BF lesions, NGF ameliorated amnesia in a water maze task and showed a tendency to increase choline acetyltransferase (CAT) activity in the fronto-parietal cortex. The amnesia and the decrease of CAT activity were not ameliorated when NGF infusion was begun 4 weeks after BF lesion formation. These observations suggest that NGF may act as a trophic and/or a protective factor on partially damaged cholinergic neurons and that the efficacy of NGF was influenced by the phase of neuronal damage. PMID- 8459652 TI - Expression and functional characterization of a rat sulfotransferase (ST1A1) cDNA for sulfations of phenolic substrates in COS-1 cells. AB - A cDNA (PST-1) isolated from a rat liver cDNA library was expressed in COS-1 cells and found to encode a form of arylsulfotransferase (termed ST1A1), which sulfated p-nitrophenol, alpha-naphthol, minoxidil, beta-estradiol and dopamine, but not dehydroepiandrosterone and cortisol. ST1A1 showed a mobility identical with a major immunodetectable sulfotransferase contained in the livers of male and female rats in Western blots. In addition, ST1A1 mRNA was detected in the liver and extrahepatic tissues by Northern blots. PMID- 8459653 TI - Effect of ibudilast on microcirculation thrombosis in rat inner ear. AB - The effect of ibudilast (0.1, 0.3 mg/kg), which has cerebral vasodilating and antiplatelet effects, was evaluated in two models of rat inner ear microcirculation thrombosis by using the photochemical reaction between green light (wave length: 540 nm) and intravenous injection of rose bengal. Furthermore, the inner ear blood flow was measured by a laser-Doppler flowmeter. In the hearing disturbance model, under anesthesia, the compound action potential of the cochlear nerve (AP) was measured by an electrocochleogram. The sound stimulus was an 8-kHz sine wave at 80 dB SPL. The AP was calculated 128 times. In the controls, the AP disappeared about 4 min after the intravenous injection of rose bengal (20 mg/kg). The time required to completely suppress the AP in the animals treated with ibudilast (0.1, 0.3 mg/kg) was significantly prolonged as compared with that in the controls. In the equilibrium dysfunction model, ibudilast (0.1, 0.3 mg/kg) reduced the time of abnormal swimming in the swimming test 24 hr after the completion of photo-illumination. Ibudilast (0.3 mg/kg) increased the inner ear blood flow during the 10-min observation period as compared with the controls, while it did not affect the mean blood pressure. In conclusion, ibudilast increased the inner ear blood flow and was effective in two models of rat inner ear microcirculation thrombosis. PMID- 8459655 TI - [Rights and obligations of the employee (II). The oath of fidelity]. PMID- 8459654 TI - [Difficult search for work. More than 1000 unemployed nurses]. PMID- 8459656 TI - [Improved patient information thanks to goal-oriented project work. End of contacts through frosted glass]. PMID- 8459657 TI - [Care and information for cancer patients. Psychological work-up of the disease: an individual process]. PMID- 8459658 TI - [Psychological defense mechanisms]. PMID- 8459660 TI - [Higher education in psychiatric nursing: and much is made clear again...]. PMID- 8459659 TI - [Rules to be carried out in order to obtain new titles and certificates. No disadvantages for already existing diplomas]. PMID- 8459661 TI - [Outpatient documentation. A new identification card in community nursing]. PMID- 8459662 TI - [Impressions from the future]. PMID- 8459663 TI - [A study trip to the American East Coast. Impressive nursing in the United States]. PMID- 8459664 TI - [Rebirth and rebirth therapy. The regenerating breath]. PMID- 8459665 TI - [Rive-Neuve: almost 5 years old]. PMID- 8459667 TI - [Evolution of organization in the nursing department. Mandates or responsibilities?]. PMID- 8459666 TI - [The end of hospices]. PMID- 8459668 TI - [Supervisory nurses in college]. PMID- 8459669 TI - [To nurse burn patients efficiently]. PMID- 8459670 TI - [Acquisition of new professional titles. No to the regulation of application]. PMID- 8459671 TI - [A mother, stricken with senile dementia, is helped by her daughter. Daughter and/or mother]. PMID- 8459672 TI - Diagnostic exercise: brown urine in a sinclair miniature pig. PMID- 8459673 TI - Isolation of Flavobacterium meningosepticum in a colony of leopard frogs (Rana pipiens). PMID- 8459674 TI - Spontaneous lateral abdominal (lumbar) hernia in a New Zealand white rabbit. PMID- 8459675 TI - Epizootic fatal dermatitis in athymic nude mice due to Staphylococcus xylosus. PMID- 8459676 TI - Interactions in the thymus leading to the development of T cells committed to the alpha beta and gamma delta lineages. PMID- 8459677 TI - Comparative susceptibility of African green monkeys (Cercopithecus aethiops) to experimental infection with Leishmania leishmania donovani and Leishmania leishmania infantum. AB - The leishmaniases are global health problems that affect both humans and animals. The availability of nonhuman primate models is desirable for such important areas as testing candidate vaccines and newly developed chemo- and immunotherapeutic agents. Visceral leishmaniasis was experimentally induced in African green monkeys (Cercopithecus aethiops) by intravenously inoculating 10(7) amastigotes/kg of body weight of either Leishmania leishmania donovani of human origin (group 1) or L. l. infantum of canine origin (group 2). The infected monkeys were monitored for 12 weeks. The monkeys developed persistent infections, became emaciated, and lost between 9 and 22% of their body weights. Splenomegaly developed by 6 to 10 weeks postinfection. All infected monkeys developed normocytic, normochromic anemia (3.5 to 3.8 x 10(6)/microliters), leukopenia (3,000 to 3,700/microliters), and neutropenia of varying severity. Hyperproteinemia with hyperglobulinemia (5.22 to 6.12 g/dl) was present in all monkeys to various degrees. Antibody responses gradually increased to peak values at 2 weeks postinfection in the L. l. donovani group and by 6 weeks postinfection in the L. l. infantum group. Lymphocyte blastogenesis proliferation responses were mildly decreased in all infected monkeys at 10 to 12 weeks postinfection. Parasite numbers were consistently higher in the livers than in spleens, and parasites were present in smears or cultures of the liver, spleen, bone marrow, and lymph nodes. Contrasting data between the two groups included 20-fold-higher parasite numbers in the livers (3.23 to 9.48 x 10(9)) and 39-fold-higher parasite numbers in the spleens (6.7 x 10(8) to 2.69 x 10(9)) of group 1. Granulomatous inflammatory reactions of various severity and intensity were observed in the liver, spleen, lymph nodes, thymus, and bone marrow of all infected monkeys. Within the granulomatous inflammatory reactions, clusters of macrophages, often containing amastigotes, were present. The morphologic changes in the bone marrow suggested a myelophthisic disease and those in lymph nodes and spleen suggested a B-cell proliferation. The clinicopathologic changes, mild suppression of cell mediated immunity, and high antibody response in all infected monkeys indicated that African green monkeys can be a useful laboratory model for studying the clinicopathologic and immunopathologic changes induced by both L. l. donovani and L. l. infantum. PMID- 8459678 TI - New Zealand white mice: an experimental model of exencephaly. AB - This is the initial report of an unusually high incidence of exencephaly in inbred New Zealand White (NZW) mice and the congenic NZW-xid strain, in which animals are homozygous for the recessive X-linked immune deficiency (xid) gene. The predominant expression of exencephaly in female pups and a disproportionate decrease in numbers of female pups in litters suggested that exencephaly was part of a continuum of lethal defects expressed preferentially in females. Genetic influence in the expression of exencephaly in NZW mice was postulated because environmental cohort controls did not express this defect. NZW mice are an additional model for studying the pathogenesis of neural tube defects. PMID- 8459679 TI - Effects of dietary vitamin E on clinical course and plasma glutamic oxaloacetic transaminase and glutamic pyruvic transaminase activities in hereditary hepatitis of LEC rats. AB - Long-Evans Cinnamon (LEC) rats are autosomal recessive mutants that develop hepatitis and hepatocellular carcinoma. Because copper accumulates in the livers of these rats, and some of their clinical and pathological features are similar to those of patients with Wilson's disease, LEC rats are proposed as an animal model of Wilson's disease. It has been thought that unbound copper generates free radicals, which act as hemolytic and hepatocytotoxic agents. To examine the effects of vitamin E as an antioxidant on hereditary hepatitis in LEC rats, we fed 3-week-old rats for 25 weeks either vitamin E-deficient, control, or vitamin E-supplemented diets which contained < 0.01 mg of total tocopherols, 2 mg of d,l alpha-tocopheryl acetate (2 I.U.), and 58.5 mg of d,l-alpha-tocopheryl nicotinate (50 I.U.), respectively, per 100 mg of feed. In males, body weight loss was first observed in the vitamin E-deficient group, and mean ages at which jaundice occurred were in the order: deficient younger than control younger than supplemented groups. The ages when plasma glutamic oxaloacetic transaminase and glutamic pyruvic transaminase activities began to increase sharply and peaked followed the same order. Thus, it is likely that free radicals are involved in jaundice and hepatitis in LEC male rats, and they are a model for studying the relationship of copper, free radicals, and hepatitis. Conversely, in females, no apparent differences in clinical and biochemical changes were observed among the three groups. Causes for the discrepancy between the sexes remain to be clarified. PMID- 8459680 TI - Hemodynamic parameters of anesthetized pigs: a comparative study of farm piglets and Gottingen and Yucatan miniature swine. AB - We studied the evolution in time of the main hemodynamic parameters in farm piglets and Gottingen and Yucatan miniature swine anesthetized with droperidol, flunitrazepam, and alpha-chloralose. Measurements included arterial pressure, heart rate, intraventricular pressure, and maximum rate of increase during contraction (dp/dt max). For each parameter and each strain of swine, we determined the mean stability period defined as the longest period of time during which the observed values ranged between their mean value +/- 15% and the mean absolute values during the stability period. In our experimental conditions, the parameters remained constant for 2 to 3.5 hours. Only minor interstrain variations were noticed. PMID- 8459681 TI - Role of glycated proteins in detecting and monitoring diabetes in cynomolgus monkeys. AB - The use of glycated serum protein testing, as measured by serum fructosamine, to detect and monitor the diabetic state in 363 cynomolgus monkeys (Macaca fascicularis) consuming either standard diet or atherogenic diet was evaluated. Reference ranges were also established in 142 rhesus monkeys (M. mulatta) and 55 stumptail monkeys (M. arctoides). Values for serum fructosamine in all species ranged from approximately 0.5 to 2 mMol/liter. After determining the colony mean for each species and diet group, four cynomolgus monkeys were found to have serum fructosamine levels more than two standard deviations above the mean, whereas all values were normal in the rhesus and stumptail monkey colonies. These four animals were determined to be diabetic by repeated fasting glucose determinations and intravenous glucose tolerance testing. Serum fructosamine values correlated significantly with glycated hemoglobin (r = 0.61, P < 0.001) and fasting blood glucose (r = 0.70, P < 0.001) determinations in all diabetic and nondiabetic monkeys. The usefulness of serum fructosamine testing to monitor longitudinal glycemic control was also evaluated. Fasting blood glucose and fructosamine values for five previously diagnosed diabetic and five nondiabetic monkeys determined at 2-week intervals over a 20-week period correlated significantly (r = 0.75, P < 0.001). In conclusion, serum fructosamine may provide an objective parameter of antecedent glycemic control in nonhuman primates. PMID- 8459682 TI - Kong toys for laboratory primates: are they really an enrichment or just fomites? AB - Simple toys as enrichment devices have been associated with a rapid decline in their use by nonhuman primates. Other facets of toy presentation have not been described previously. For example, a comparison of the effect(s) of an enrichment device between two facilities should be validated if enrichment recommendations are to be made that affect diverse research facilities across the country. Additionally, a comparison of two methods of presentation (one highly accessible to the animal and the other less accessible) of the same enrichment device for potential differences in efficacy could provide direction in implementing an enrichment program based on simple toys. The handling of enrichment devices by nonhuman primates can lead to the spread of microbial contamination. The typical enrichment program rotates enrichment devices among animals to maximize the variety of stimuli available to each primate in the most economic manner. An adequate sanitation program is therefore pivotal to minimizing the potential for enrichment devices to be fomites. We conducted three experiments that addressed these issues. The results confirmed that, although the presence of a simple toy reduced behavioral pathology, there was variability in behavioral effect for an enrichment technique between facilities. Two methods of presentation (on floor and suspended) of a simple toy did not produce any significant differences in use. Finally, we demonstrated that microbial growth can persist on enrichment devices after they have been sanitized in a commercial cagewasher. PMID- 8459683 TI - Ivermectin eradication of pinworms from rats kept in ventilated cages. AB - Studies using rats that were naturally infested with Syphacia muris and kept in forced-air, individually ventilated cages showed that ivermectin given orally at a dose of 2 mg/kg for three treatments at 7- or 9-day intervals was eradicative. Paired ivermectin treatments given at 7- or 9-day intervals were ineffective in eliminating parasitism. Pinworm eggs persisted on the perianal region of rats for up to 17 days and eggs were also present in soiled contact bedding within cages and on surfaces within the animal room. Anal tapes as a diagnostic test had 88% sensitivity in detecting pinworms. PMID- 8459684 TI - Use of superovulated mice as embryo donors for ES cell injection chimeras. AB - We examined whether superovulation can be used to improve the efficiency of donor embryo collection in embryonic stem cell injection chimera experiments. Superovulation of prepuberal C57BL/6 mice was compared with spontaneous ovulation of mature mice with respect to production and survival of blastocysts. Our results indicate that, compared with spontaneous ovulation, superovulation results in an increased number of blastocysts per female with no difference in viability when transferred to outbred Swiss Webster foster mothers. The advantage of using superovulated females, in terms of maintaining smaller numbers of both females and stud males, is discussed. PMID- 8459685 TI - Measurement of cardiovascular and renal function in unrestrained hamsters. AB - We describe a preparation for measuring blood pressure, left ventricular end diastolic pressure, heart rate, and renal excretory variables (volume, electrolytes, glomerular filtration rate) in hamsters. The new approach offers an advantage over previously described methods by eliminating the problems associated with restraint. Hamsters were surgically implanted with venous and arterial catheters. A specially constructed bladder catheter, which allows flushing to minimize errors due to dead space and permits urine collection without restraining the animals, was also implanted. The hamsters were allowed to recover from surgery for 3 hours before being studied in a specially designed lucite housing unit. Representative results were obtained in cardiomyopathic and healthy hamsters. PMID- 8459686 TI - Diagnostic exercise: skin infarction in rats. PMID- 8459687 TI - Control of hyperglycaemia in diabetic rabbits by a combination of implants. AB - Insulin demand varies with meal intake and physical activity. In this study the feasibility of using two implants to meet varying insulin demands was tested in rabbits with alloxan-induced diabetes. One group of severely diabetic rabbits was maintained on a basal dose released by a 50-mg implant made of a compressed admixture of 15% insulin in palmitic acid. The other group of mildly diabetic rabbits required no basal dose implant, but displayed a transient hyperglycaemia as well upon challenge. The supplemental dose was provided by another silicone implant with reservoirs containing 6 mg of compressed insulin. Serous fluid entered the 100 microliters internal volume of the silicone implant slowly through an orifice, and dissolved some of the solid insulin. When required, sideways compression of this second implant over the abdominal skin fold of the rabbit delivered the supplemental dose. Typically, a severely diabetic rabbit on a basal dose implant exhibited a transient hyperglycaemia after drinking sweetened water, which raised the blood glucose from 5.4 +/- 1.3 mmol l-1 to 14.0 +/- 0.5 mmol l-1 for 3 to 4.5 h. In the three test runs, the supplemental bolus of insulin from the silicone implant interrupted the expected rise in blood glucose at 6.1 +/- 2.2 mmol l-1 within 1 to 2 h, which then decreased to 3.0 +/- 0.2 mmol l-1 for 4 to 5 h before returning to the basal level. A mildly diabetic rabbit showed a blood glucose level of 10.5 +/- 1.9 mmol l-1 without the basal dose implant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8459688 TI - Multielectrode spiral cuff for ordered and reversed activation of nerve fibres. AB - In this paper we present the modelling, design, and experimental testing of a nerve cuff multielectrode system for selective activation of fibres in superficial peripheral nerve trunk regions which is capable of activating fibres in physiological order. The multielectrode system consists of 45 platinum electrodes embedded within a self-curling spiral silicone sheet organized in fifteen longitudinal groups consisting of three electrodes spaced equidistally around the circumference of the cuff. Electrodes in the centre band acted as stimulating cathodes while the two electrodes of the same group in the two outer bands were connected together and corresponded to the position of a particular cathode, serving as anodes to block the nascent action potentials by membrane hyperpolarization. The interpolar distance was 6 mm on both sides, resulting in a total cuff length of about 20 mm. The cuff was constructed with a diameter to fit the size of the dog sciatic nerve. Preliminary animal testing of the nerve cuff was performed on the sciatic nerve of a Bigley female dog. In the 45-electrode stimulation system, biphasic cathodic first pulses with quasitrapezoidal-shaped cathodic and square anodic parts were delivered through the particular group of tripolar electrodes to effect both selective stimulation of motor axons within the gastrocnemius muscle fascicle, and differential block by membrane hyperpolarization. The test was repeated using rectangular cathodic first biphasic current pulses delivered monopolarly on the central electrode of the same group while connected anodes were replaced by a common anode situated elsewhere in the surrounding tissue. In both experiments an isometric torque in the ankle joint elicited by the gastrocnemius muscle was measured and compared.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8459689 TI - Breast compression: a preliminary study. AB - X-Ray mammography is the technique employed to image breast tumours; it is the gold standard for both diagnosis and screening. To increase the sensitivity of the test and to reduce the dose of X-radiation, breast compression is used. The effect of squeezing a simple model of a breast in which there is an idealized spherical tumour volume is investigated; the cases where the lesion has both a smaller, and a larger compressibility than the surrounding tissues are considered. Surface strain is computed as a function of the deformation of the lesion from its spherical shape. Evidence from earlier studies is adduced to show that when the lesion is malignant care should be exercised to avoid the possibility of disseminating cancer cells by the application of compressive forces. PMID- 8459690 TI - A mathematical model of the right ventricular muscle geometry and mass. AB - An understanding of the geometry of the right ventricular (RV) free wall is imperative for both modelling its mechanics and assessing its mass by imaging techniques such as echocardiography. In this paper, a new model of the RV free wall geometry is discussed in which the wall is assumed to have a parabolic long axis and a circular short-axis curvature respectively. By use of analytic geometry, mathematical expressions for RV surface area, volume and mass were derived. In vitro model validation was carried out in the following manner: (1) echocardiographic images of 16 isolated calf hearts were obtained; (2) measurements were made from the images to determine the parameters required by the model; (3) wall mass was determined by use of these parameters; and (4) the calculated wall mass was then compared with actual RV wall mass (determined by weighting). The model was found to be very accurate for determination of RV free wall mass (R = 0.92); it should prove useful in the study of the stress-strain relationships for the RV and for precise quantitative assessment of RV free wall mass. PMID- 8459691 TI - Wave digital matched filter for electrocardiogram preprocessing. AB - Digital filters play an important role in electrocardiography. Digital filter algorithms having low sensitivity to finite word-length errors are generally desirable. Wave digital filters (WDFs) are a class of filters having excellent sensitivity properties. A wave digital matched filter (WDMF) for ECG preprocessing is presented here. PMID- 8459692 TI - Strain gauge plethysmography for the detection of deep venous thrombosis. AB - Deep venous thrombosis is a widely recognized medical problem which results in significant morbidity and mortality. Venography is the current 'gold standard' diagnostic test for deep venous thrombosis; however it is costly, invasive and is unnecessarily performed in 50% of cases. This paper describes a self-contained, non-invasive system for automatic venous occlusion plethysmographic measurement and analysis. An examination of 274 symptomatic limbs was conducted using strain gauge plethysmography and a subsequent venographic examination was then performed. The plethysmographic results were then compared with venography so as to develop a means of discrimination for thrombotic and non-thrombotic limbs. Strain gauge plethysmography using the Belfast DVT Screener yielded a sensitivity of 100% and a sensitivity of 66.3% for proximal segment DVT. The efficacy of the discriminatory algorithm was then tested for the diagnosis of DVT in a further 101 symptomatic patients. A sensitivity of 94.7% and a specificity of 81.7% were observed for strain gauge plethysmography for proximal segment thrombosis in this patient group. The Belfast DVT Screener is highly sensitive for deep venous thrombosis and may be used to reduce the need for venography, which is of benefit to both the patient and clinician. PMID- 8459693 TI - Motion measurement with high-speed video. AB - A new kinematic measurement system based on a high-speed video system, combined with a computer-assisted evaluation for the analysis of gait patterns, is described. The system allows both a reviewable visual assessment in slow motion (up to 1000 frames s-1 as well as automatic measurement of the kinematics of body segments. Specially developed software, which uses a pattern search algorithm and an additional subpixel correction, results in a deviation of less than 0.1% (without considering the lens nonlinearity). For most cases the recognition and tracking of temporarily concealed markers is also achieved. The results of the computer-assisted high-speed video analysis are being applied in rehabilitation programmes to increase the objectivity of standard movements, e.g. gait analysis of people with artificial limbs. PMID- 8459694 TI - A feasibility study of a filtration type autotransfusion device. AB - This paper describes a feasibility study of a disposable autotransfusion device for blood salvage during surgery. The goal was to concentrate hemolyzed blood at 20% hematocrit to 50% while reducing the plasma free hemoglobin concentration from 10 to 1.5 g/l. The device should have a total membrane area of less than 0.6 m2 and should be able to process ten 500 ml blood bags. The processing time for each blood bag should not exceed 5 min. The basic idea was to use several polypropylene hollow fibre plasma filters of 0.1 m2 in series with saline addition between them. Since the mean pore size is 0.5 microns, anticoagulant and plasma hemoglobin can pass freely across the membrane and their concentration is reduced by dilution. The process was first modelled using mass balance equations for red blood cells and plasma hemoglobin in order to find the best device configuration (number of filters and dilutions). It was found that a three filter system could theoretically meet the requirements, if the last filter had a larger surface area (0.3 m2). Some experiments permitted us to prove the validity of this model and to define fully the third filtration stage. Finally, it was shown that the treatment of a 500 ml blood bag required three filtration stages (whose surface areas were respectively 0.1, 0.1 and 0.3 m2) and the use of 750 ml of saline solution added between the filters. This configuration also offers the possibility of using a vacuum driving force instead of pumps, so that the device becomes completely disposable. PMID- 8459695 TI - Computer generation of complex arterial tree models. AB - Detailed models of binary branching arterial trees can be generated on a computer by using a new optimization technique; additional branches are successively added, while given conditions of perfusion pressure, total flow and terminal pressure are fulfilled. The vessel radii at each branching obey certain bifurcation laws, and the process of growing the tree is governed by minimizing a target function. The structure thus generated may serve as substrate for the future simulation of haemodynamics in highly detailed arterial trees. PMID- 8459696 TI - Quantitative photoplethysmography: Lambert-Beer law or inverse function incorporating light scatter. AB - Finger blood volume is commonly determined from measurement of infra-red (IR) light transmittance using the Lambert-Beer law of light absorption derived for use in non-scattering media, even when such transmission involves light scatter around the phalangeal bone. Simultaneous IR transmittance and finger volume were measured over the full dynamic range of vascular volumes in seven subjects and outcomes compared with data fitted according to the Lambert-Beer exponential function and an inverse function derived for light attenuation by scattering materials. Curves were fitted by the least-squares method and goodness of fit was compared using standard errors of estimate (SEE). The inverse function gave a better data fit in six of the subjects: mean SEE 1.9 (SD 0.7, range 0.7-2.8) and 4.6 (2.2, 2.0-8.0) respectively (p < 0.02, paired t-test). Thus, when relating IR transmittance to blood volume, as occurs in the finger during measurements of arterial compliance, an inverse function derived from a model of light attenuation by scattering media gives more accurate results than the traditional exponential fit. PMID- 8459697 TI - Foot microcirculation and blood rheology in diabetes. AB - Diabetes mellitus is associated with circulatory abnormalities. The blood flow in the skin of the dorsum of the foot and haemorheological variables were measured in 36 subjects. They were divided into three equal groups of diabetic patients: those with neuropathy, and both age and sex matched non-diabetic subjects; all were characterized by age, duration of diabetes and blood biochemistry. High and low shear rate blood viscosities were measured; aggregation was characterized using a Myrerene Aggregometer. The microcirculation in the skin of the dorsum of the foot was measured using a laser Doppler flowmeter. Measurements were made at room temperature with the subjects supine with the leg horizontal, and then with the lower leg vertical; the measurements were repeated at 42 degrees C. Both diabetic groups had significantly increased low shear whole blood viscosity compared with normal subjects. The aggregation index was significantly greater in diabetic neuropaths than normal subjects. There were significant differences in the depth of vasomotor activity between the three groups, with the diabetic neuropaths commonly showing no motor activity at room temperature. The only significant correlations were between equilibrium laser Doppler values with the limb horizontal and both the low and high shear whole blood viscosities. PMID- 8459698 TI - Unstable states in four-point walking. AB - The presently utilized walking patterns in paraplegic subjects with complete spinal cord injury (SCI) are compared by the help of graphic representations. Improved four-point gait assisted by functional electrical stimulation (FES) and crutches is proposed by introducing unstable states into the walking sequence. The unstable states are defined as passive phases of walking where the centre of mass (COM) is gravity driven in the direction of progression. The unstable state is described by a simple inverted pendulum model. Kinematic measurements of the unstable state were performed in normal and paraplegic subjects. PMID- 8459699 TI - Optimized 3D coordinate reconstruction from paired stereographs using a calibrated phantom. AB - A refinement to a previously described three-dimensional reconstruction algorithm based on point identification in calibrated non-orthogonal radiograms (stereo pairs) is described. The modification involves a computation of the focal point magnitude of the point in three dimensions, analogous to focusing in two dimensions, as well as the most likely location of the target point in 3-space; the focal point magnitude may be thought of as the precision of the point identification. Multiple observer studies of the same stereopair can be used to estimate three-dimensional reconstruction accuracy by providing an average location and a mean distance from average. Both measures are useful parameters for initial selection of bone landmark references and for error propagation studies. PMID- 8459700 TI - Pressure-volume relation in the right ventricle. AB - The concept of body force (force/unit volume of muscle), which has been suggested as an explanation for the mechanical contraction of the left ventricle, is now applied to the right ventricle. The results indicate that the same mathematical formalism can be applied to a description of the pressure-volume relation and the ejection mechanism in both the right and left ventricles. PMID- 8459701 TI - Effects of pH and temperature on the scanning Soret oximeter. AB - A new optical measurement technique based on spectral scanning (the scanning Soret oximeter) has previously been described. The technique has now been tested under extremes of physiological pH and temperature, the effects of which are shown to be negligible. PMID- 8459702 TI - Comment on: Qualitative holographic study of hemi-pelvic deformation caused by loading different hip prostheses. PMID- 8459703 TI - Pre-term infant volume measurements by acoustic plethysmography. AB - An acoustic plethysmograph has been developed to provide routine total body volume measurements of pre-term (1.5-3.0 kg) infants. It operates near 50 Hz and is excited by band-limited 25 Hz span noise. Excitation, measurement, analysis, and environment are computer controlled for greater accuracy, speed, and objectivity in volume determinations. Performance tests produced volume measurements with a mean per cent error (+/- SD) of 0.77 +/- 0.66% for two phantoms with volumes of 2880 and 2130 cm3. Ten, one-minute volume measurements were obtained for 14 infants over a 20 to 30 min period. Their mean density was 1.061 +/- 0.028 g cm-3 and their weight ranged from 1294 to 2025 g. PMID- 8459704 TI - Stereoradiogrammetric technique for estimating alignment of the joints in the hand and wrist. AB - A method and apparatus for quantitative measurement of the alignment and motion of the joints of the hand in three dimensions has been developed using stereoradiogrammetric principles. Alignment in planes of flexion-extension and radial-ulnar deviation can be determined to within 2.5 degrees; rotation about the long axis of the metacarpals or phalanges is more difficult to determine, and can be measured to within 7 degrees. Stereo views subtending angles in the range of 40 degrees were found to optimize the total system accuracy. PMID- 8459705 TI - In memoriam Selden D. Bacon 1909-1992. PMID- 8459706 TI - The influence of time, gender and group size on heavy drinking in public bars. AB - Four hypotheses are tested focusing on the small group basis of legal intoxication. A sample of 1,996 isolates and groups gathering to drink at a 12% random sample of 565 bars in a two-county metropolitan area was observed using a stratified random time sampling schedule. Multiple regression was used to test the hypotheses. The hypothesis that group size affects proportion of group drinking heavily during one visit to a bar was not supported. Average group alcohol consumption, group gender composition and average duration of group stay in bar do affect proportion of group drinking heavily. PMID- 8459707 TI - Modeling social influences on public drinking. AB - This article combines the qualitative tradition of naturalistic observations with quantitative multivariate methods to quantify the relationships between drinker characteristics, group composition, duration of the drinking period and alcohol consumption. Employing observational data on over 6,000 drinkers collected in six on-premise licensed establishments in California, structural equation regression methods were used to estimate the simultaneous effects of duration of the drinking period and total consumption on each other, controlling for patron characteristics and group composition. Results from all six establishments indicate that consumption is higher in larger groups because of longer drinking times at the establishment and not because of any direct effect of consumption on length of the drinking period. Group composition effects on consumption are also indicated since females in mixed drinking groups tend to reduce the alcohol consumption of males, but not the group as a whole. PMID- 8459708 TI - Understanding U.S. alcohol consumption with social and economic factors: a multivariate time series analysis, 1950-1986. AB - The contribution of social and economic variables to changes in per capita alcohol consumption occurring between 1950 and 1986 is examined within a multivariate time series analysis framework. Specifically, we consider the net effects of family income, age structure of the population, marital instability, female labor force participation, real alcohol price and daily life routines on total alcohol consumption. Our findings indicate that changes in the population age structure and in daily life routines were associated with predicted changes in consumption over the period studied. They also indicate associations between marital instability and female labor force participation and consumption, although in the direction contrary to our prediction. Unlike a number of previous studies in which economic variables were found to be the major determinants of consumption trends, we find that family income and the price of alcohol play a minor role in the model we estimated. These results indicate that social structural factors have greater utility for our understanding of alcohol consumption patterns, and, by implication, for attempts to reduce alcohol-related social problems, than do economic factors. PMID- 8459709 TI - Seasonal variation in survey and sales estimates of alcohol consumption. AB - Time variation of drinking is substantial and has an effect on aggregate estimates of consumption. In this article it is shown that because of a considerable seasonal variation in consumption (+/- 20%) a serious bias in annual consumption estimates can be expected in surveys with a limited time frame. The present study analyzes drinking data collected in the general population of the Netherlands from March 1985 through December 1985 (including Christmas and New Year's Eve). Since it was expected that sensitivity to temporal fluctuations might not be equal for different methods of measurement, several indices of consumption were compared. Although the assessed seasonal effect varies indeed across types of measurement, across male and female subsample and across types of alcoholic beverage, the general tendency is for consumption to be highest in the spring season and lowest in the autumn. Sales figures fluctuate accordingly. It is evident that the risk of biased estimates is larger the shorter the time frame of the survey. Seasonal variation was highest in the frequency domain. Furthermore, exclusion from the time frame of collective holidays, during which people drink more often and more per occasion (viz., Christmas), increases the risk of biased estimates. Even estimates of abstention, but also regular heavy drinking among women, appear to vary considerably over the three seasons in this study. The main conclusion is that results of comparisons of survey data on drinking, particularly those over time, are more or less invalid if the respective time frames of the surveys do not correspond. PMID- 8459710 TI - Family history models of alcoholism: age of onset, consequences and dependence. AB - The association of a family history of alcoholism to susceptibility to alcoholism has been well documented over the past 3 decades. The classification of a family history of alcoholism commonly involves the division of subjects into family history positive and negative groupings. However, diverse definitions are used to define positive family histories. These diverse definitions of family alcoholism impede the comparison of results from different studies. The present study evaluates several classification schemes and compares them with a new method for the analysis of family patterns of alcoholism (FPA). A sample of 220 male alcoholic veteran inpatients were assessed for age of onset of alcoholism, consequences of drinking and the severity of their dependence. Multiple regression equations were estimated for several dichotomous family history models and each model was evaluated against a comparable FPA model that included the same family members. Comparisons of the classification models with the equivalent FPA analysis model facilitated comparisons of the contribution of each family history designation to changes in amount of explained variance. In all instances, the FPA analyses explained more variance than did the comparable dichotomous family history models. In addition, the FPA analyses reveal the relative explanatory power of each family member and indicate that maternal relatives often have a more important contribution than has been indicated previously. PMID- 8459711 TI - Alcohol use among male and female Native American adolescents: patterns and correlates of student drinking in a boarding school. AB - This study examined the patterns and correlates of alcohol use in a Native American boarding school. Specifically, stressful life events, social support and emotional distress were associated with quantity as well as frequency of alcohol use in this population. A sample of 188 students (52% female) in grades 9-12 attending a boarding school in the midwest were administered self-report measures of these above constructs as part of a larger battery. Family support, and to some degree stressful life events and emotional distress, correlated significantly with alcohol use. The implications of these findings for Native American adolescents in general, and in a boarding school population specifically, are discussed. The need for longitudinal research to explore further the temporal sequence of depression, stressful life events and social support in relation to alcohol use is addressed. PMID- 8459712 TI - The development of alcoholics' and heavy drinkers' consumption: a longitudinal study. AB - Results are reported from two prospective longitudinal studies of heavy drinkers and alcoholics who have received treatment. The present study focuses on the drinking habits of subjects who have been interviewed four times after the end of treatment. The data uncover substantial changes in heavy drinkers' and alcoholics' consumption level over time, and these observed changes are only partly explainable in terms of measurement error and short-term fluctuations. Changes show signs of accumulation over time. This suggests that heavy drinkers' and alcoholics' consumption level is very unstable over longer periods. The signs of systematic progression are weak. No convincing evidence for loss of control is found, and neither is there convincing evidence for a strong and persistent progression towards heavier drinking. At all levels substantial changes are found, and these are nearly equally strong in both directions. It is concluded that the observed pattern of change more resembles an indeterministic (or stochastic) process than a systematic natural history of a disease. PMID- 8459713 TI - The impact of alcohol consumption on parent-child relationships in families of alcoholics. AB - The impact of alcohol consumption upon parent-child relationships was assessed longitudinally in eight father-son dyads. Univariate and bivariate time series analyses of daily reports for 85 days revealed a number of significant effects. Most importantly, results suggest that not all children are similarly affected by fathers' day-to-day drinking. The authors discuss potential explanations of how parental drinking affects parent-child relationships on a day-to-day basis. PMID- 8459714 TI - Alcoholism in treatment-seeking cocaine abusers: clinical and prognostic significance. AB - Two hundred ninety-eight treatment-seeking and 101 community cocaine abusers were interviewed using the Schedule for Affective Disorders and Research Diagnostic Criteria. Alcoholism was the most frequently diagnosed current and lifetime psychiatric disorder in both samples. Several findings from this study converge with recent evidence which suggests a particularly strong relationship between cocaine abuse and alcoholism that may differ from other types of alcohol-drug comorbidity. First, rates of alcoholism among cocaine abusers doubled those of comparable samples of opioid addicts. Second, while virtually all cocaine abusers in this sample reported some alcohol use during the past month, a lifetime diagnosis of alcoholism was associated with more severe cocaine dependence. Third, the onset of alcoholism followed the onset of drug dependence for the majority of alcoholic cocaine abusers, a pattern which contrasts that typically seen in other types of drug-alcohol comorbidity and suggests that cocaine abuse may increase vulnerability to secondary alcoholism. Prognostically, cocaine abusers who were alcoholic at baseline interview were more likely to remain alcoholic at 1-year follow-up but did not differ from nonalcoholic cocaine abusers on other measures of outcome. PMID- 8459715 TI - An examination of cluster-based classification schemes for DUI offenders. AB - This study examines the utility of cluster-based classification schemes for DUI offenders. Variables from previous empirical typologies and multiple domains were used in a series of cluster analyses in order to examine replicability across independent samples, across clustering algorithms and across sets of psychometric indicators. The arbitrary nature of cluster solutions and the external validity of cluster-based schemes, with respect to an outcome criterion constructed synthetically from earlier research, was examined. Only three of eight cluster techniques (Ward's, K means, and complete linkage) yielded meaningful results. For these techniques, replicability was poor across samples, algorithms and sets of psychometric indicators. Results indicated that identified clusters were arbitrary. Although external validity analysis yielded positive results, the possibility that external validity was a function of underlying dimensions was discussed, as were other implications of the findings. PMID- 8459716 TI - Visual-spatial learning in nonalcoholic young adults with and those without a family history of alcoholism. AB - Visual-spatial learning in young adult nonalcoholic men and women with (FH+) and those without (FH-) a family history of alcoholism was investigated using nonsense shapes of high and low verbal association value. Four groups of FH+ and FH- men and women, 16 subjects in each group, were tested. The male FH+ group required significantly more trials to reach learning criterion and made more errors than the male FH- group; the FH effect was not significant in females although similar trends were present. Women exhibited significantly poorer visual spatial learning compared to the men. High compared to low verbal association shapes were learned in fewer trials with fewer errors by all groups. There were no significant FH by verbal association interactions, indicating that the impaired visual-spatial learning in the FH+ men could not be ascribed to the meaningfulness dimension of the nonsense shapes. These results suggest that the impaired visual-spatial learning found in adult children of alcoholics (ACOAs) might be due in part to premorbid cognitive deficits. PMID- 8459717 TI - An econometric technique to remove unobserved variables that bias the relationship between alcohol and blood pressure. AB - We use econometric techniques to consider whether the statistical association between drinking and blood pressure among men may be due, in part, to the constitutional hypothesis. The constitutional hypothesis holds that the same unobserved genetic or personality factors that affect blood pressure will affect the amount of alcohol consumed. Our sample is restricted to men because most investigations for women have revealed a weak to nonexistent positive, and sometimes a negative, association. Data are drawn from the National Health and Nutrition Examination Survey, 1971-1975. The econometric technique requires fitting three equations using two-stage least squares or multiple regressions. The first equation explains how much people drink. The second and third equations explain fluctuations in systolic and diastolic blood pressures using information on the predicted values of the drinking variable from the first equation. Our results suggest that, after accounting for unobserved constitutional factors as well as other observed covariates such as obesity, salt intake, schooling and so on, the strength of the statistical association between high blood pressure and heavy drinking in men drops only slightly by 8% (diastolic) and 23% (systolic). Thus, a strong statistically significant result remains after removing the unobserved variables bias. PMID- 8459718 TI - Effects of privatization of wine sales. PMID- 8459719 TI - Activation of an apomorphine behavior pattern by cocaine: a new behavioral test for drug substitution. AB - In current tests for drug substitution using the 2-choice operant bar press paradigm, an animal can be trained to respond differentially between an interoceptive drug state stimulus vs. saline. Despite the long history and extensive number of investigations, the interpretation of such test results, nevertheless, is limited by number of potential sources of stimulus drug effects which can occur with repeated drug administration but which cannot be distinguished by this paradigm: (1) local effects at the injection site; (2) peripheral effects; (3) central activity effects; and/or (4) sensory-motor dysfunctional effects. By using a video-image analysis of behavior in an intact animal model and a pavlovian drug treatment protocol, new, spontaneous but environmentally contingent and stable behavior patterns emerge selectively in the paired treatment group with repeated drug administration which can be used as a behavioral marker to assess dose-response effects and drug substitution test results with a novel drug. A study with repeated administration of the DA agonist apomorphine and with a drug substitution assessment by a cocaine drug test is presented as a reference example to illustrate the new response-based methodological approach to the study of central mechanisms mediating the stimulus and response effects of drugs. Additionally, the observed efficacy of cocaine to activate a complex acquired behavioral pattern unique to repeated apomorphine treatment supports a critical role for dopaminergic mechanisms in the mediation of cocaine induced stereotypy. PMID- 8459720 TI - A simple intrapipette salt bridge. AB - A simple method is described for achieving a salt bridge within a patch pipette. The tip of the pipette is filled with a Cl(-)-free solution that bathes the membrane patch. Above this is a Cl(-)-containing solution that surrounds the recording Ag/AgCl wire electrode. Addition of 0.07% (w/v) agarose to the solution in the tip prevents bulk mixing of the 2 phases within the pipette. This configuration makes it possible to remove Cl- from the membrane surface but maintain it at the electrode surface. The presence of the Cl(-)-free phase in the bottom of the patch pipette does not reduce the electrical stability of the recording electrode. PMID- 8459722 TI - Thermoimaging of the brain. AB - A new method of neuroimaging is proposed that is based on the recording of weak changes in infra-red radiation from the brain. Thermoencephaloscopy (TES) uses a combination of thermovision and digital image processing techniques and allows one to make a dynamic investigation of the thermal fields of the cerebral cortex through an unopened skull. Today the method is characterized by: (i) differential thermosensitivity of up to 0.002 degrees C; (ii) instrumental temporal resolution 40 ms (25 thermomaps/s); (iii) time of the temperature measurement in the part of an object that correspondes to one pixel on digital thermomap is equal to 2.4 microseconds; (iv) instrumental spatial resolution of up to 70 microns/pixel; and (v) the thermomap size is 10880 pixels (128 x 85). TES allows detection of an appearance and study of topography and dynamics of the small (from 140 to 300 microns) and precisely localized zones of activation or deactivation of the cerebral cortex that are modally and regionally specific with respect to stimuli modality and parameters and to the state of an animal. Up to now such studies were performed with white rats, rabbits, cats, monkeys and humans under different kinds of sensory stimulation, motor tasks, conditioning (associative learning). Fast thermowaves spreading over the brain cortex along specific trajectories were revealed under sensory stimulation. The mechanisms of the recorded phenomena are discussed: (i) joule heating produced by ion currents through membranes of activated neurones; (ii) metabolic thermoproduction; (iii) thermal convection by the local cerebral blood flow; and (iv) thermodipole formation in the cortical foci with changed lCBF. PMID- 8459721 TI - The tungstate-stabilized tetramethylbenzidine reaction for light and electron microscopic immunocytochemistry and for revealing biocytin-filled neurons. AB - A peroxidase reaction product that can be easily distinguished from standard diaminobenzidine (DAB) reaction products is needed for pre-embedding electron microscopic double-antibody labelling studies. Benzidine dihydrochloride (BDHC) and gold-substituted silver peroxidase reactions are unsatisfactory for double labelling because they lack sensitivity and reliability and/or compromise ultrastructure. We show here that light and electron microscopic immunocytochemistry can be done with a modification of the tungstate-stabilized tetramethylbenzidine (TMB) reaction (Weinberg and Van Eyck 1991) which yields a crystalline reaction product. With this method, we have obtained excellent immunolabelling for a variety of antigens, including tyrosine hydroxylase, enkephalin, serotonin, Fos protein and retrogradely transported cholera toxin B subunit (CTB). The TMB-tungstate reaction is useful for ultrastructural double labelling because the crystals contrast well with the amorphous product of diaminobenzidine reactions. The TMB-tungstate reaction is more sensitive and reliable for immunocytochemistry than the benzidine dihydrochloride reaction and gives better ultrastructure than the gold-substituted silver peroxidase reaction. We also show that neurons filled with biocytin by intracellular injection can be visualized with TMB-tungstate for either light (LM) or electron (EM) microscopy. PMID- 8459723 TI - Visualization of neurons filled with biotinylated-lucifer yellow following identification of efferent connectivity with retrograde transport. AB - A new method is described that allows identification of neurons by retrograde transport, intracellular injection of biotin-labeled Lucifer Yellow, and a histochemical reaction of the biotin. Cells in the inferior colliculus that project to the ipsilateral thalamus are identified by injection of rhodamine labeled latex beads into the medial geniculate body and retrograde transport in vivo. Several days later, the brains are fixed with aldehydes, and the inferior colliculus is cut on a vibratome. The rhodamine-labeled cells are observed with epi-fluorescent optics, impaled with intracellular pipettes under visual control, and injected with 9% Lucifer Yellow dilithium salt and 1% Lucifer Yellow cadaverine biotin-X. The biotinylated Lucifer Yellow is visualized by incubation of the slice overnight in avidin-biotin-HRP complex in the presence of 0.1% Triton X-100 at 4 degrees C. A diaminobenzidine reaction with simultaneous cobalt and nickel intensification follows. This method produces well-filled neuronal cell bodies, dendrites, and spines for light microscopic analysis. The non fluorescent reaction product in these intracellularly filled cells may permit transmitter immunohistochemistry and synaptic fine structure to be studied in combination with neural connections and dendritic morphology. PMID- 8459724 TI - A triangular conditioning voltage wave does not influence spontaneous neuronal activity in the rat striatum. AB - A triangular potential wave applied shortly before each measuring triple pulse has been used in in vivo voltammetric experiments to ensure the maintenance of a high level of stability and sensitivity in the carbon fiber electrode. To investigate whether a triangular wave (0- +/- 1500 mV, 10 V/s slope) and a consecutive triple pulse affect spontaneous neuronal firing, extracellular recordings were made in the rat striatum at a distance of about 200-300 microns from the carbon fiber electrode while these potentials were being delivered. No significant change in the rate of spontaneous firing was found. A triangular pulse has proven to be very effective in lengthening the measurement lifetime of the carbon fiber electrode without interfering with the spontaneous activity of striatal neurons. PMID- 8459725 TI - A technique for recording the activity of brain-stem neurones in awake, unrestrained cats using microwires and an implantable micromanipulator. AB - A new technique is described which is suitable for long-term recording of the activity of neurones in the brain of an awake, unrestrained cat. By using telescopic electrodes, neurones up to 39 mm from the cranial surface can be reached with a miniature micromanipulator which is small enough to be left in place between recording sessions. The most stable recordings have been obtained with electrodes made from microwire, with which units have been held for up to 8 h. PMID- 8459726 TI - [Overlooked spinal fractures in Bechterew's disease--a continuation]. PMID- 8459727 TI - [It would be easier without physicians!]. PMID- 8459728 TI - [The tax-payer and the patient must both be winners!]. PMID- 8459729 TI - [Problems of interpretation in vascular surgery]. PMID- 8459730 TI - [The climacteric woman]. PMID- 8459732 TI - [Dramatic increase of diphtheria in Russia]. PMID- 8459731 TI - [Rabies in the perspective of the EEC. Time to look over the routines in Sweden?]. PMID- 8459733 TI - [Ovarian hyperstimulation syndrome. Diagnosis and prevention are extremely important]. PMID- 8459734 TI - [Criminality--a fatal disease?]. PMID- 8459735 TI - [The man behind the method: Nils Lundberg. He measured the classical "plateau waves"]. PMID- 8459736 TI - [Pain relief in pulpitis through hyperventilation. A personal observation]. PMID- 8459737 TI - [Research fraud. Manipulated conclusions on therapy of otitis in children]. PMID- 8459738 TI - [The Board of Drug Control starts inspections to prevent fraud in tests]. PMID- 8459739 TI - [Lumbosacral rhizotomy. Surgical alternative in the CP syndrome with spastic diparesis]. PMID- 8459740 TI - [Bone marrow transplantation. A EEC-project with unrelated donors saves more and more people]. PMID- 8459741 TI - [Newly discovered organism behind diarrhea. All patients had recently been abroad]. PMID- 8459742 TI - [Dissertation focusing on a new debate on principles]. PMID- 8459743 TI - Ear foreign-body removal: a review of 98 consecutive cases. AB - Although patients with external auditory canal foreign bodies present frequently, there is scant literature on the topic other than case reports. A study of 98 consecutive patients referred over a 1-year period to otolaryngologists at a large urban county hospital was undertaken. Fifty-seven percent of these patients were over 12 years of age. A data form was completed by the otolaryngology resident removing the foreign body. Fifty-three percent of the cases had undergone one or more previous attempts at removal prior to the otolaryngologist's attempt, usually by an emergency room physician. Method of removal included use of a microscope in only 6% of previous attempts, while otolaryngologists used a microscope in 91%. Canal wall lacerations were present in 48% of patients following previous attempts at removal by other health-care professionals, but were found in only 4% of removals by an otolaryngologist. Recommendations include use of a microscope for removal and referral to an otolaryngologist if the foreign body is not readily removed by the primary-care physician. PMID- 8459744 TI - Middle ear disease in young children with sensorineural hearing loss. AB - Early identification of children with sensorineural hearing loss (SNHL), coupled with the provision of appropriate conventional amplification constitute important elements of a (re)habilitative strategy. Often overlooked, however, is the problem posed by recurrent and chronic middle ear disease in the child with coexisting SNHL. This study focuses on 437 (237 boys and 200 girls) consecutive patients with bilateral SNHL, in the moderate range or poorer, who were diagnosed prior to age 5 years at Boys Town National Research Hospital. The mean threshold shift with effusion was 25.0 dB at 250 Hz, 28.5 dB at 500 Hz, 29.5 dB at 1000 Hz, 24.5 dB at 2000 Hz, and 27.5 dB at 4000 Hz. During a median follow-up period of 3.21 years, 154 (35.2%) of these children required surgical placement of tympanostomy tubes because of the severity of middle ear disease and its impact on auditory acuity. Accurate determination of the degree and audiologic configuration of a SNHL may be seriously hindered by a coexisting middle ear effusion. If initial findings indicate the presence of a middle ear effusion, measures of auditory function must be repeated after the effusion has been resolved by medical and/or surgical intervention. PMID- 8459745 TI - Nerve excitability testing: technical pitfalls and threshold norms using absolute values. AB - Percutaneous stimulation of the facial nerve is used widely in tests to judge the severity and prognosis of facial paralysis. Several test paradigms are used including nerve excitability threshold (NET), the maximum stimulation test (MST), and electroneuronography (EnoG). Consistent technique and careful control of variables are essential to achieve accurate test results. The sources of variability examined in this study were age, gender, body weight, and the use of electrode paste; the NET was used as the test method. The facial NET in 120 adults without a history of facial paralysis increased linearly with age (P = .0004) and with body weight (P < .0001) and was higher in men than in women adjusted for age and weight (P = .0001). The mean NET +/- SD was 0.7 +/- 0.27 mA in the upper division using the eyelid twitch as an end point, and 1.2 +/- 0.40 mA in the lower division. There was no statistically significant difference in the results between sides. The NET was falsely elevated by the use of electrode paste, presumably due to current shunting away from the nerve. Based on the technique described herein, an absolute NET of > or = 1.25 mA in the upper division or an absolute NET > or = 2.0 mA in the lower division of the human facial nerve is statistically abnormal. These norms are not applicable to grossly obese patients or patients with facial edema or inflammation. Statistical norms allow the NET results to be reported on a continuous scale rather than the dichotomous scale used in the past. The predictive power of the NET will be greatly enhanced by basing test interpretation on both statistical and clinical significance. PMID- 8459746 TI - Facial nerve morbidity following parotid surgery for benign disease: the Cleveland Clinic Foundation experience. AB - Standard surgical management for benign tumors of the parotid gland requires either superficial, subtotal, or total parotidectomy with preservation of the facial nerve. Although this approach is effective in minimizing recurrence, the resultant facial nerve morbidity is seldom addressed. Two hundred fifty-six consecutive patients who underwent parotid surgery for benign neoplasia at this institution in the past 15 years are reviewed, with attention to postoperative facial nerve function. Immediate dysfunction was frequently encountered (46.1%), but permanent dysfunction was uncommon (3.9%). The incidence of long-term dysfunction may be higher in revision cases and when an extended (total or subtotal) parotidectomy is performed. PMID- 8459747 TI - Significance of tumor thickness in soft palate carcinoma. AB - Tumor thickness is an important prognostic factor in tumors outside of the upper aerodigestive tract, such as cutaneous melanoma, colorectal carcinoma, and cervical carcinoma. Some studies have also suggested that tumor thickness may have similar prognostic value in the upper aerodigestive tract. This study examined the relationship between tumor thickness (measured with an ocular micrometer) and nodal disease and that between tumor thickness and survival in 44 patients with soft palate epidermoid carcinoma. There was a significant correlation between tumor thickness and nodal disease. None of the 24 lesions less than or equal to 2.86 mm had cervical adenopathy. All of the 15 lesions greater than or equal to 3.12 mm had palpable adenopathy. Tumor thickness correlated more directly with nodal disease than did T stage. Thicker lesions were associated with poorer survival. Tumor thickness is an important parameter in the head and neck and deserves further study. PMID- 8459748 TI - The effects of cyclosporin A on transplanted rat allografts. AB - Since 1983, Cyclosporin A (CsA) has been the most successful primary drug in preventing rejection of organ transplants. This study was designed to determine the efficacy and dose response of CsA in preventing rejection of LBNF-1 rat allografts to Lewis recipients. Four groups of animals were studied. Group I served as the control, and groups II, III, and IV were given daily intramuscular doses of CsA for 1 month. The groups were given doses of 5 mg/kg, 7.5 mg/kg, and 10 mg/kg, respectively. Sixty-eight animals were transplanted to get eight viable transplanted animals at 1 month in each CsA group. Laryngeal viability was assessed with both clinical and histological parameters. Groups II, III, and IV had representative clinically viable larynges. The histology varied and had some correlation with CsA dosage. Group II evidenced changes ranging from mild to severe rejection. Group III was more homogeneous with the most severe change being characterized as mild-to-moderate rejection. Group IV was the most uniform with all representative specimens showing only limited infiltration of inflammatory cells with intact mucosa and submucosal glands (mild rejection). None of the CsA groups evidenced the squamous metaplasia characteristic of the control group. CsA can prevent rejection of laryngeal allografts from LBNF-1 donors to Lewis recipients. PMID- 8459749 TI - Metabolic activity of the central auditory structures following prolonged deafferentation. AB - The goal of this work was to evaluate, using autoradiographic techniques, the effects of variable periods of deafness on resting and evoked metabolic activity in central auditory structures elicited by direct electrical cochlear nucleus (CN) stimulation. Thirty-five pigmented guinea pigs, divided into five groups, underwent acute implantation of bipolar electrodes in the CN. One group was not deafened and served as hearing controls. The other four groups were deafened using an established protocol of sequential kanamycin/ethacrynic acid treatment and were tested at 4 weeks, 9 weeks, 16 weeks, and 15 months after deafening. Threshold currents for eliciting evoked middle latency responses (EMLRs) with direct CN stimulation were not significantly different between hearing and deafened groups. Autoradiographic data showed progressive reduction of the evoked metabolic response with incremental periods of deafferentation. Nevertheless, central auditory structures remained responsive to direct electrical stimulation of the CN. These data indicate that direct CN stimulation remains capable of activating the auditory tract despite prolonged periods of deafness. PMID- 8459750 TI - Facial nerve monitoring in surgery for congenital auricular atresia. AB - Surgery for congenital auricular atresia places the facial nerve at risk because of its potential aberrancy; iatrogenic facial paralysis is a well-known potential risk. Five cases of congenital auricular atresia are presented. All patients had intraoperative monitoring of the facial nerve. The facial nerve was found to be abnormally displaced, usually due to hypoplasia of the tympanic ring. Preoperative and postoperative facial nerve function was unchanged by surgery. Facial nerve monitoring is an important adjunct in congenital ear surgery because it allows for early and precise identification of the nerve in the absence of normal surgical landmarks and provides for continuous monitoring of the nerve. PMID- 8459751 TI - Vascular decompression surgery for severe tinnitus: selection criteria and results. AB - Seventy-four patients were operated on within a period of 10 years to treat incapacitating tinnitus; 72 underwent microvascular decompression (MVD) of the intracranial portion of the auditory nerve, and 2 underwent section of the eighth nerve close to the brain stem. Of those who underwent MVD, 2 had no change in symptoms and later also underwent section of the eighth nerve near the brain stem. Two patients did not return for follow-up. Of the 72 remaining patients, 13 (18.1%) experienced total relief from tinnitus, 16 (22.2%) showed marked improvement, 8 (11.1%) showed slight improvement, 33 (45.8%) had no improvement, and 2 (2.8%) became worse. The patients who experienced total relief and those who showed marked improvement had experienced their tinnitus for an average of 2.9 years and 2.7 years, respectively; those who showed slight improvement and those who had no improvement had experienced their tinnitus for a longer time before the operation (mean, 5.2 and 7.9 years, respectively). Of the 72 patients who were operated on and followed, 32 were women. Of these, 54.8% experienced total relief from tinnitus or marked improvement, while only 29.3% of the men showed such relief or improvement. Selection of the patients for operation was mainly based on patient history and, to some extent, on auditory test results (brainstem auditory evoked potentials [BAEP], acoustic middle ear reflexes, and audiometric data). PMID- 8459752 TI - Inhalation of platelet-activating factor increases respiratory resistance in rats: determination by means of an astograph under nonanesthetized conditions. AB - Intratracheal administration of platelet-activating factor (PAF) to dogs, baboons, and humans has been shown to induce hyperreactivity of the airways and contraction of the smooth muscle. However, it has not yet been reported whether intratracheal administration of PAF to rats induces hyperreactivity. In the present study, the authors estimated the respiratory resistance of rats during intratracheal administration of PAF in order to evaluate the reactivity of the airways to PAF. In both the nonsensitized group and the sensitized group of rats, intratracheal administration of PAF induced an increase in respiratory resistance. The results obtained clarify that responsiveness to PAF exists in the airways of rats. PMID- 8459753 TI - The changing clinical presentation of acoustic tumors in the MRI era. AB - The application of magnetic resonance imaging (MRI) scanning in the diagnosis of acoustic neuroma (AN) has increased the relative incidence of smaller tumors and has impacted on the typical clinical presentation of AN patients. The charts of 126 patients treated at the University of California, San Francisco for newly diagnosed AN from 1986 to 1990 were reviewed. Twenty-four percent of tumors fell into the smallest size category (< 1 cm); this was a substantial improvement over earlier series. However, 16% of tumors remained undiagnosed until they achieved large size (> 3 cm). The incidence of hearing loss, dysequilibrium, headache, facial numbness, and diplopia all increased with increasing tumor size, while the incidence of vertigo decreased. Diagnosticians should not overemphasize "typical" symptom complexes, as substantial variability in clinical manifestations exists. An improved awareness by clinicians of the variability of AN presentation will improve diagnostic efficiency and continue the trend toward earlier diagnosis of these lesions. PMID- 8459754 TI - Atypical hearing loss in acoustic neuroma patients. AB - Audiologic data from 126 patients treated at the University of California, San Francisco for newly diagnosed acoustic neuromas (ANs) from 1986 to 1990 were reviewed. Subjectively normal hearing was present in 15% of patients and was most frequent in patients with small (< 1 cm) tumors. Only 4% had objectively normal hearing on the basis of speech reception threshold (SRT), speech discrimination score (SDS), and high-frequency pure-tone loss. This was most frequent in patients with < 1 cm tumors. Abnormal but symmetrical hearing is usually not considered to be indicative of a unilateral AN. In the present series, 7% of patients with ANs possessed symmetrical hearing. High-frequency asymmetry was a more sensitive indicator of the presence of an AN than differences in either SRT or SDS. The clinician must be aware of the relatively high incidence of atypical audiologic findings in acoustic tumor patients. PMID- 8459755 TI - Facial neuroma of the cerebellopontine angle and the internal auditory canal. AB - Four cases of facial neuroma confined to the cerebellopontine angle and internal auditory canal are presented. Prior to surgery, three of these were diagnosed as an acoustic tumor. At operation the true diagnosis of facial neuroma was made. The operative procedure was recorded on film and videotape. The magnetic resonance imaging (MRI) and computed tomography (CT) scans were reviewed retrospectively. In the first three cases the tumor was not centered on the axis of the internal auditory canal (IAC), as would be typical of an acoustic neuroma, but instead occupied a position eccentric to this axis. In one case, this eccentricity was marked. A similar appearance in the fourth case enabled the true diagnosis of facial neuroma to be made before surgery. The postoperative behavior of the tumors was unpredictable. The patient with the largest tumor, which was debulked at operation, did not develop a facial palsy. However, a patient with a small tumor which was not biopsied, developed a delayed but complete paralysis from which she subsequently recovered. This small series suggests that it may be possible, by use of the appropriate imaging technique, to diagnose, preoperatively, a cerebellopontine angle facial neuroma which is otherwise indistinguishable from an acoustic neuroma. PMID- 8459756 TI - Resistance to respiratory airflow of the extrapulmonary airways. AB - Resistances to respiratory airflow of nasal, pharyngeal, laryngeal, and tracheobronchial airway segments were determined by computer processing of digitized differential pressure and flow signals in four healthy, awake, male adults seated and breathing spontaneously at rest, exclusively through decongested noses. Resistances of the nasal and pharyngeal segments in Pa/cm3 per second averaged 0.139 (SD +/- 0.044) and 0.081 (SD +/- 0.051), respectively, with no resistive evidence of compliance with airflow pressures. The laryngeal segment exhibited the reciprocal of compliance, expiratory resistances exceeded those of inspiration, averaging 0.125 (SD +/- 0.037) and 0.035 (SD +/- 0.013), respectively (.005 < P < .01). Tracheobronchial resistances during spontaneous resting breathing were too small to record reliably at the calibration used, and values augmented by voluntary hyperventilation averaged only 0.012 (SD +/- 0.004). Laryngeal expiratory resistance approximated one fifth of the sum total of respiratory airflow resistances (including the pulmonary airways) and the authors suggest that, in addition to contributing to expiratory airflow braking, partial laryngeal closure induces orifice flow. This nonlaminar flow regime promotes the mucosal contact and mixing that enables greater than 30% of heat and water to be recovered from expiratory air by the human pharynx and nose. PMID- 8459757 TI - Endoscopic frontal recess and frontal sinus ostium dissection. PMID- 8459758 TI - Electromyographic recording of tensor and levator veli palatini muscles: a modified transnasal insertion method. PMID- 8459760 TI - Directory of Otolaryngological Societies. PMID- 8459759 TI - The lateral crural turnover graft: correction of the concave lateral crus. PMID- 8459761 TI - Pioneer otologist Fowler praised. PMID- 8459762 TI - Transition-state regulators: sentinels of Bacillus subtilis post-exponential gene expression. AB - When Bacillus subtilis encounters a nutrient-depleted environment, it expresses a wide variety of genes that encode functions in alternative pathways of metabolism and energy production. Expression of these genes first occurs during the transition from active growth into stationary phase and is controlled by a class of proteins termed transition-state regulators. In several instances, a given gene is redundantly controlled by two or more of these regulators and many of these regulators control genes in numerous different pathways. The AbrB, Hpr and Sin proteins are the best-studied examples of these regulatory molecules. Their role is to prevent inappropriate and possibly detrimental functions from being expressed during exponential growth when they are not needed. They serve as elements integrating sporulation with ancillary stationary-phase phenomena and appear to participate in the timing of early sporulation events and in fine tuning the magnitude of gene expression in response to specific environmental conditions. PMID- 8459763 TI - Protein HU binds specifically to kinked DNA. AB - We have purified the main four-way junction DNA-binding protein of Escherichia coli, and have found it to be the well-known HU protein. HU protein recognizes with high-affinity one of the angles present in the junction, a molecule with the shape of an X. Other DNA structures characterized by sharp bends or kinks, like bulged duplex DNAs containing unpaired bases, are also bound. HU protein appears to inhibit cruciform extrusion from supercoiled inverted repeat (palindromic) DNA, either by constraining supercoiling or by trapping a metastable interconversion intermediate. All these properties are analogous to the properties of the mammalian chromatin protein HMG1. We suggest that HU is a prokaryotic HMG1-like protein rather than a histone-like protein. PMID- 8459764 TI - Isolation of dnaJ, dnaK, and grpE homologues from Borrelia burgdorferi and complementation of Escherichia coli mutants. AB - The heat-shock proteins DnaJ, DnaK, and GrpE are involved in the replication of various species of DNA in Escherichia coli, in addition to their roles in other processes, including protein disaggregation and export. We have cloned the Borrelia burgdorferi homologues of these genes. DNA sequence analysis revealed an open reading frame encoding a protein that is 62% identical to the E. coli DnaK protein. Genes homologous to the E. coli grpE and dnaJ genes, encoding products 28% and 39% identical to their homologues, are located up- and downstream, respectively, of the B. burgdorferi dnaK gene. No obvious promoters were detected in the sequenced DNA, although a potential transcription terminator was found downstream of the dnaJ gene, so these three genes may form an operon, perhaps with a fourth gene located upstream of the grpE gene. The grpE homologue complemented an E. coli grpE mutant and the dnaJ homologue complemented an E. coli dnaJ mutant, whereas the B. burgdorferi dnaK gene did not complement dnaK mutants. PMID- 8459765 TI - Identification and characterization of adhesive factors of Clostridium difficile involved in adhesion to human colonic enterocyte-like Caco-2 and mucus-secreting HT29 cells in culture. AB - Experiments reported in this communication showed that the highly toxinogenic Cd 79685, Cd 4784, and Wilkins Clostridium difficile strains and the moderately toxinogenic FD strain grown in the presence of blood adhere to polarized monolayers of two cultured human intestinal cell lines: the human colonic epithelial Caco-2 cells and the human mucus-secreting HT29-MTX cells. Scanning electron microscopy revealed that the bacteria interacted with well-defined apical microvilli of differentiated Caco-2 cells and that the bacteria strongly bind to the mucus layer that entirely covers the surface of the HT29-MTX cells. The binding of C. difficile to Caco-2 cells developed in parallel with the differentiation features of the Caco-2 cells, suggesting that the protein(s) which constitute C. difficile-binding sites are differentiation-related brush border protein(s). To better define this interaction, we tentatively characterized the mechanism(s) of adhesion of C. difficile with adherence assays. It was shown that heating of C. difficile grown in the presence of blood enhanced the bacterial interaction with the brush border of the enterocyte-like Caco-2 cells and the human mucus-secreting HT29-MTX cells. A labile surface-associated component was involved in C. difficile adhesion since washes of C. difficile grown in the presence of blood without heat shock decreased adhesion. After heating, washes of C. difficile grown in the presence of blood did not modify adhesion. Analysis of surface-associated proteins of C. difficile subjected to different culture conditions was conducted. After growth of C. difficile Cd 79685, Cd 4784, FD and Wilkins strains in the presence of blood and heating, two predominant SDS-extractable proteins with molecular masses of 12 and 27 kDa were observed and two other proteins with masses of 48 and 31 kDa disappeared. Direct involvement of the 12 and 27 kDa surface-associated proteins in the adhesion of C. difficile strains was demonstrated by using rat polycolonal antibodies pAb 12 and pAb 27 directed against the 12 and 27 kDa proteins. Indeed, adhesion to Caco 2 cell monolayers of C. difficile strains grown in the presence of blood, without or with heat-shock, was blocked. Taken together, our results suggest that C. difficile may utilize blood components as adhesins to adhere to human intestinal cultured cells. PMID- 8459766 TI - DNA sequence, structure and gene expression of mycobacteriophage L5: a phage system for mycobacterial genetics. AB - Genetic studies of Mycobacterium tuberculosis and other mycobacterial pathogens have suffered from the lack of a sophisticated genetic system. To address this issue we have developed a viral system through a detailed characterization of mycobacteriophage L5, a temperate phage that infects both fast- and slow-growing mycobacteria. We describe here the complete DNA sequence of the L5 genome and initial characterization of L5 virion structure and gene expression. In addition to providing a genetic 'tool-box' for the mycobacteria we find that L5 offers a new paradigm for dsDNA phages, being phenotypically temperate but employing genetic strategies for phage growth usually associated with lytic bacteriophages. PMID- 8459767 TI - Superinfection immunity of mycobacteriophage L5: applications for genetic transformation of mycobacteria. AB - Mycobacteriophage L5 is a temperate phage of the mycobacteria that forms stable lysogens in Mycobacterium smegmatis. We show here that the 183-amino-acid product of L5 gene 71 confers immunity to L5 superinfection, is required for maintenance of the lysogenic state and contains a helix-turn-helix DNA-binding motif- properties associated with repressors of temperate phages. We have utilized these observations to demonstrate the use of L5 gene 71 as a selectable marker for genetic transformation of the mycobacteria. Significantly, the use of L5 gene 71 as a selectable gene avoids the requirement for antibiotic-resistance genes providing an important tool for manipulation of the pathogens Mycobacterium tuberculosis and Mycobacterium avium, and for the construction of recombinant BCG vaccines. PMID- 8459768 TI - Bacterial cholesterol oxidases are able to act as flavoprotein-linked ketosteroid monooxygenases that catalyse the hydroxylation of cholesterol to 4-cholesten-6-ol 3-one. AB - A new metabolite of cholesterol was found in reaction mixtures containing cholesterol or 4-cholesten-3-one as a substrate and extra- or intracellular protein extracts from recombinant Streptomyces lividans and Escherichia coli strains carrying cloned DNA fragments of Streptomyces sp. SA-COO, the producer of Streptomyces cholesterol oxidase. The new metabolite was identified as 4 cholesten-6-ol-3-one based on comparisons of its high-performance liquid chromatography, gas chromatography/mass spectrometry, infrared and proton-nuclear magnetic resonance spectra with those of an authentic standard. Genetic analyses showed that the enzyme responsible for the production of 4-cholesten-6-ol-3-one is cholesterol oxidase encoded by the choA gene. Commercially purified cholesterol oxidase (EC 1.1.3.6.) of a Streptomyces sp., as well as of Brevibacterium sterolicum and a Pseudomonas sp., and a highly purified recombinant Streptomyces cholesterol oxidase were also able to catalyse the 6 hydroxylation reaction. Hydrogen peroxide accumulating in the reaction mixtures as a consequence of the 3 beta-hydroxysteroid oxidase activity of the enzyme was shown to have no role in the formation of the 6-hydroxylated derivative. We propose a possible scheme of a branched reaction pathway for the concurrent formation of 4-cholesten-3-one and 4-cholesten-6-ol-3-one by cholesterol oxidase, and the observed differences in the rate of formation of the 6-hydroxy ketosteroid by the enzymes of different bacterial sources are also discussed. PMID- 8459769 TI - Iron-dependent stability of the ferredoxin I transcripts from the cyanobacterial strains Synechococcus species PCC 7942 and Anabaena species PCC 7937. AB - The effect of iron on ferredoxin I specific mRNA levels was studied in the cyanobacterial strains Synechococcus sp. PCC 7942 (Anacystis nidulans R2) and Anabaena sp. PCC 7937 (Anabaena variabilis ATCC 29413). In both strains addition of iron to iron-limited cells resulted in a rapid increase in ferredoxin mRNA levels. To investigate the possible role of the ferredoxin promoter in iron regulation, a vector for promoter analysis in Synechococcus PCC 7942 strain R2 PIM9 was constructed, which contains the ferredoxin promoter fused to the gene encoding beta-glucuronidase (GUS) as reporter. Neither the Synechococcus nor the Anabaena ferredoxin promoter was able to direct iron-regulated GUS activity in Synechococcus R2-PIM9, indicating that transcription initiation is not responsible for the iron-dependent ferredoxin mRNA levels. Determination of the half-life of the ferredoxin transcript in iron-supplemented and iron-limited cells revealed that, in both strains, the ferredoxin transcript is much more stable in iron-supplemented cells than in iron-limited cells. These results lead to the conclusion that in these strains, iron-regulated expression of the ferredoxin I gene is mediated via differential mRNA stability. PMID- 8459770 TI - Amplified expression of a transcriptional pattern formed during development of Anabaena. AB - The cyanobacterium Anabaena responds to nitrogen deprivation by producing heterocysts, cells specialized for nitrogen fixation, at well-spaced intervals along its filaments. The gene hepA, required for heterocyst maturation, is expressed in response to nitrogen deprivation, prior to visible differentiation. A spatial pattern of hepA expression indistinguishable from the eventual pattern of heterocysts was made visible by fusing the hepA promoter to luxAB, which encodes bacterial luciferase. Because the resulting signal did not greatly exceed instrumental background, T7 RNA polymerase was used to increase luminescence. The hepA promoter was fused to the gene for that polymerase, and a promoter recognized by that polymerase was fused to luxAB. Filaments containing these two fusions showed spaced luminescing cells many hours before differentiation became discernible morphologically. PMID- 8459771 TI - Electrophoretic karyotype and gene assignment to resolved chromosomes of Trichoderma spp. AB - A molecular karyotype for three different Trichoderma species (T. harzianum, T. viride, and T. reesei) was determined by using two different systems: countour clamped electric-field and rotating-electrode electrophoresis. Six chromosomal DNA bands were observed in T. harzianum and T. reesei and five in T. viride. The sizes of these molecules were estimated by their mobility relative to the Schizosaccharomyces pombe chromosomes and ranged between 2.2 and 7.4 megabase pairs (mbp). The estimated genome sizes range from 31 to 39 mbp. A number of genes were located in the different chromosomes by means of Southern analysis. The implications of these findings are discussed. PMID- 8459772 TI - The RpoS sigma factor relieves H-NS-mediated transcriptional repression of csgA, the subunit gene of fibronectin-binding curli in Escherichia coli. AB - Curli encoded by the curlin subunit gene, csgA, are fibronectin- and laminin binding fibres expressed by many natural Escherichia coli and E. coli K-12 strains in response to low temperature, low osmolarity and stationary-phase growth conditions. Curli expression is dependent on RpoS, a sigma factor that controls many stationary phase-inducible genes. Many commonly used K-12 strains carry an amber mutation in rpoS. Strains able to form curli carry an amber suppressor whereas curli-negative E. coli K-12 strains, in general, are sup0. Introduction of SupD, SupE, or supF suppressors into sup0 strains resulted in expression of temperature-regulated curli. In curli-deficient, RpoS- E. coli K-12 strains, csgA is transcriptionally activated by mutations in hns, which encodes the histone-like protein H-NS. Curli expression, fibronectin binding, and csgA transcription remain temperature- and osmoregulated in such double mutants. Our data suggest that RpoS+ strains, and hence curli-proficient strains of E. coli K 12, are relieved for the transcriptional repression mediated by the H-NS protein upon accumulating RpoS as cells reach stationary phase. PMID- 8459773 TI - Bacterial interspersed mosaic elements (BIMEs) are present in the genome of Klebsiella. AB - Bacterial interspersed mosaic elements (BIMEs) constitute a family of highly repetitive sequences containing palindromic units (PUs), also called repetitive extragenic palindromes (REPs). BIMEs were originally described in Escherichia coli and Salmonella typhimurium. We show here, by determining the nucleotide sequence of two intergenic regions of Klebsiella pneumoniae, by computer searches, and by hybridization, that sequences with similar characteristics are found in the genome of several Klebsiella species. This reinforces the idea that BIMEs play general and important roles in enterobacteria such as in the organization of the bacterial chromosome. PMID- 8459774 TI - Characterization of a virG mutation that confers constitutive virulence gene expression in Agrobacterium. AB - Transformation of plants by Agrobacterium tumefaciens is mediated by a set of virulence (vir) genes that are specifically induced by plant signal molecules through the VirA/VirG two-component regulatory system. The plant signal is transmitted from VirA to VirG by a cascade of phosphorylation reactions followed by the sequence-specific DNA binding of the VirG protein to the vir gene promoters which then activates their transcription. In this report, we describe a VirG mutant which is able to activate vir gene expression independently of the VirA molecule and the two plant signal molecules, acetosyringone and monosaccharides. A strain of Agrobacterium containing this virG gene but lacking a functional virA gene was able to induce tumours on all three plants that were tested. A single amino acid change of asparagine (N) to aspartate (D) at position 54, adjacent to the site of VirG phosphorylation, aspartate 52, resulted in this constitutive phenotype. In vitro phosphorylation experiments showed that the mutant protein cannot be phosphorylated by VirA, suggesting that the negative charge resulting from the N to D switch mimics the phosphorylated conformation of the VirG molecule. The same amino acid change in the virG gene of the supervirulent strain A281 also resulted in a constitutive phenotype. However, the vir genes were not induced to high levels when compared with the levels of the constitutive virG of strain A348. PMID- 8459775 TI - High-affinity binding of the basement membrane protein collagen type IV to the crystalline virulence surface protein array of Aeromonas salmonicida. AB - The surface of the fish pathogen Aeromonas salmonicida is covered by a paracrystalline array (the A-layer) which is a virulence factor for the organism. Quantification of the ability of A. salmonicida cells to bind collagen types I and IV in a 125I-radiolabelled liquid-phase assay showed that A-layer-positive cells bound high levels of collagen type IV, but significantly lower levels of collagen type I. Collagen type IV binding was confirmed using non-radiolabelled enzyme-linked immunosorbent assays. 125I-Collagen type IV binding was rapid, specific, saturable, high affinity, and essentially irreversible by unlabelled collagen type IV. The A-layer was responsible for collagen type IV binding because binding was inactivated by selective removal of the A-layer at pH 2.2, and neither isogenic A-layer-deficient A. salmonicida mutants nor strains of Aeromonas hydrophila possessing a morphologically similar paracrystalline array bound this basement membrane protein. PMID- 8459776 TI - The minCD locus of Bacillus subtilis lacks the minE determinant that provides topological specificity to cell division. AB - A key event of the sporulation process in Bacillus subtilis is the asymmetric cell division that divides the developing cell into two unequal compartments. To examine the function of vegetative cell division genes in this developmental division, we isolated and characterized the B. subtilis counterpart to the Escherichia coli minicell operon minB, which governs correct placement of the division septum. Starting from the closely linked spoIVF locus, we used walking methods to isolate the region of the B. subtilis chromosome proximate to the divIVB minicell locus. DNA sequence analysis found two open reading frames whose predicted products had significant identity to the E. coli MinC cell division inhibitor and the MinD ATPase activator of MinC, and disruption of minCD function generated a minicell phenotype in B. subtilis. Notably, no homologue to the E. coli MinE topological specificity element was found in the B. subtilis minCD region. The B. subtilis min genes were part of an operon transcribed from a major promoter more than 2.5 kb upstream from minC. An internal promoter immediately upstream from minC was dependent on RNA polymerase containing sigma-H and was active at the onset of sporulation. However, neither minC nor minD function was absolutely required for sporulation and, by implication, for asymmetric septum formation. PMID- 8459777 TI - Characterization of mutations in divIB of Bacillus subtilis and cellular localization of the DivIB protein. AB - Four temperature-sensitive mutations in the divIB gene of Bacillus subtilis have been localized to the region corresponding to the C-terminal half of the 263 residue DivIB protein. Antiserum was raised to the 80% C-terminal portion lying on one side of a putative transmembrane (hydrophobic) segment, and used to examine aspects of the nature and localization of the DivIB protein in the cell. A single DivIB species of a size equal to the full-length protein encoded by the divIB gene was detected in wild-type cells. Cell fractionation studies established that DivIB is associated preferentially with the cell envelope (membrane plus cell wall), with approximately 50% being released into solution upon treatment of cells with lysozyme under conditions that yield protoplasts. Of the remaining 50%, approximately half remained firmly associated with the membrane fraction. On the basis of the 'positive-inside rule' of von Heijne (1986) it is suggested that the topology of membrane-bound DivIB is such that the long C-terminal portion is directed to the outside and the smaller N-terminal portion to the inside of the cell. DivIB in protoplasts was rapidly degraded by proteinase K under conditions where there was no general proteolysis of the cytoplasmic proteins. This is consistent with its absence from the cytoplasm, and with the predicted membrane topology. Septum positioning in a divIB null mutant, which grows as filaments at temperatures of 30 degrees C and below, was found to be normal. It appears that DivIB is needed for achieving the appropriate rate of initiation of septum formation at normal division sites. It is proposed that the C-terminal portion of DivIB, localized on the exterior surface of the membrane and in juxtaposition to the peptidoglycan, normally interacts with another protein (or proteins) to initiate septum formation. PMID- 8459778 TI - Effects on cell morphology of growing Pseudomonas aeruginosa, Enterobacter cloacae and Staphylococcus aureus in subinhibitory concentrations of p aminobenzoic acid. AB - Light microscopy and electron microscopy studies with Enterobacter cloacae, Pseudomonas aeruginosa and Staphylococcus aureus grown in the presence of subinhibitory concentrations of p-aminobenzoic acid indicate that p-aminobenzoic acid may have a direct or indirect effect on the cell walls. The morphological effects of p-aminobenzoic acid varied with different bacterial species. E. cloacae grown in the presence of p-aminobenzoic acid produced filaments while P. aeruginosa cells were elongated and had thicker peripheral cell walls. S. aureus had increased overall cell size and thicker transverse cell walls. PMID- 8459779 TI - Copper accumulation by a strain of Pseudomonas putida. AB - A study on the copper accumulation by resting cells of copper-resistant bacteria, isolated from activated sludge and electroplating effluent, was conducted. The best selected strain, identified as Pseudomonas putida II-11, retained copper ions, Cu(II), as high as 6.5% of its dry weight. Bacterial cells grown in the sulphate-limiting medium had the highest copper removal capacity [RC, mg of Cu(II)/g of dry cells], while the presence of glucose or sodium azide did not affect Cu(II) RC of the bacterial cells. A possible mechanism of Cu(II) accumulation by this bacterium is suggested. PMID- 8459780 TI - Evidence for association of bacteriocinogenic activity with membrane vesicles of Thermus rubens. AB - Thermus rubens has previously been reported to exhibit bacteriocin-like antagonism against other members of the genus Thermus when assayed via the deferred antagonism technique. Bacteriocin activity was not detectable in various age batch culture supernatants assayed by simple spotting procedures. Successful cell-free isolation was accomplished by way of a procedure employing French press disruption of T. rubens cells. Ultrafiltration and molecular exclusion chromatographic studies ascribed a high molecular weight to the agent which was found to be completely precipitable by ammonium sulphate. Activity was totally sedimentable upon ultracentrifugation. Transmission electron microscopic examination of column fractions containing high specific activity revealed numerous circular, apparently trilaminar, structures indicative of membrane vesicles. PMID- 8459781 TI - Flow chamber study of the adhesion of Prevotella intermedia to glass after preconditioning with mutans streptococcal species: kinetics and spatial arrangement. AB - The adhesion kinetics and spatial arrangement of a clinical isolate of Prevotella intermedia on bare glass and on glass which had been previously exposed to Streptococcus rattus or Streptococcus cricetus were studied using a parallel plate flow system and image analysis. When S. cricetus was the preconditioning organism the initial deposition rate and efficiency of P. intermedia were reduced even though very few S. cricetus adhered during flow with P. intermedia. Preconditioning with S. rattus had less effect on the adhesion behaviour of P. intermedia despite the fact that more S. rattus cells adhered than S. cricetus cells. Small differences in both the stationary state adhesion and in the final spatial arrangements were evident under the three experimental conditions. S. cricetus negatively influences initial deposition of subsequent P. intermedia adhesion possibly by the production of a biosurfactant or by leaving 'microbial footprints'. This interference is eventually overcome resulting in a similar stationary state adhesion of P. intermedia as found without S. cricetus preconditioning. Furthermore, the flow chamber system employed here proved uniquely suited for studying cell-cell interactions in initial adhesion. PMID- 8459782 TI - Effect of NaCl on the growth and morphology of Saccharomycopsis fibuligera. AB - The effect of NaCl on mycelial growth of Saccharomycopsis fibuligera was examined. Cells were able to grow in medium containing 1 M or 2 M NaCl after adaptation to the salt under standing culture conditions. It took more time to adapt to 2 M NaCl than to 1 M NaCl. Hollow-looking regions in the cells increased during incubation for 20 days in medium without salt, but diminished in cells incubated in medium containing either of the two concentrations of NaCl. The mycelial cells incubated in the medium containing salt were slimmer, and bubble shaped, and malformed cells were observed. The extent of the change was greater in 2 M NaCl than that in 1 M NaCl. NaCl protected cells from leaking, and produced malformed cells. PMID- 8459783 TI - Effects of environmental enrichment on cortical depth and Morris-maze performance in B6D2F2 mice exposed prenatally to ethanol. AB - Pregnant mice were fed a liquid diet with 25% of the calories as ethanol from day 5 to 17 of gestation; controls received equivalent amounts of diet with maltose dextrin substituted isocalorically for the ethanol. Two male weanlings from each litter were assigned randomly to an enriched or isolated environmental condition. After 6 weeks in these environments measures of brain growth were obtained, including thickness of frontal, parietal, and occipital cortex (study 1), or their behavioral capabilities were assessed in a Morris water maze (study 2). Ethanol decreased birth weight (both studies), postweaning body weight (study 2), and brain weight (study 1), while the enriched animals in both studies were heavier. Ethanol decreased the thickness of the occipital cortex only. All groups demonstrated learning by showing a decrease in latency to locate the hidden platform over the 5 days of testing; this was supported by their spending most time in the target quadrant during the probe trial. The latencies of the enriched animals were shorter than the isolated; covariance analysis indicated that this was not due solely to their faster swimming speed. PMID- 8459784 TI - Relationship between serum cholinesterase activity and the change in body temperature and motor activity in the rat: a dose-response study of diisopropyl fluorophosphate. AB - Risk assessment of the neurotoxicology of organophosphate (OP) pesticides calls for a thorough understanding of the relationship between tissue cholinesterase (ChE) activity and changes in behavioral and autonomic responses to OP treatment. To address this issue, motor activity, core and skin temperature, and serum ChE activity were measured 2 h after rats of the Long-Evans strain were treated with the OP, diisopropyl fluorophosphate (DFP) at a dose of 0, 0.1, 0.25, 0.5, 0.75, 1.0, 1.25, and 1.5 mg/kg (SC). DFP doses > or = 0.25 mg/kg led to significant decreases in serum ChE activity, whereas doses of > or = 0.5 mg/kg caused reductions in motor activity and body temperature. The highest dose of DFP caused an increase in tail skin temperature, indicating an elevation in skin blood flow. A hockey stick regression analysis was used to determine threshold inhibition in ChE activity associated with depressions in motor activity and colonic temperature. The threshold serum ChE activity, relative to controls for inhibition of motor activity and reduction in body temperature was 46%. A wide range in individual motor activity and colonic temperature responses was noted when the inhibition in ChE activity exceeded threshold levels. This may be indicative of marked genetic variability to ChE inhibition. That is, rats appear to be either responsive or unresponsive when subjected to extreme inhibition in ChE activity. This pattern has been reported in other rodents and may represent a fundamental aspect of ChE toxicity. PMID- 8459785 TI - Neuropsychological correlates of low-level lead exposure in school-age children: a prospective study. AB - The neuropsychological underpinnings of lead-associated deficits in general cognitive abilities and academic achievement were investigated in a cohort of 148 middle and upper-middle class 10 year-olds. Scores on a battery of neuropsychological tests were examined in relation to blood lead levels measured at birth and ages 6, 12, 18, 24, 57 months, and 10 years. Although numerous indices of the level, nature, and variability to children's performance on the WISC-R were associated with blood lead level measured at 24 months of age (pb24), relatively few significant associations were noted between specific measures of neuropsychological functions and pb24 (or other blood lead measurements). Some evidence was found for an association between recently measured lead levels and qualitative aspects of a child's performance (e.g. perseveration). The presence of more significant lead effects on broad-based measures of functioning than on neuropsychological tests may be attributable to the use of insensitive measures of neuropsychologic function, limitations in coverage provided by the tests, the nature of lead's CNS impact, or individual differences in biologic vulnerability to lead. PMID- 8459786 TI - Assessment of behavioral effects of tetrachloroethylene using a set of time series analyses. AB - A systematic approach to the analysis of time-series data for spontaneous locomotor activity in the rat was developed to evaluate the behavioral effects of chemical substances. Chronogram, spectral analysis, analysis of the slope of fluctuation, and the cosinor method were used to analyze data obtained by continuously recording spontaneous locomotor activity in the rat. Under synchronized conditions, a circadian period of 24 h was observed and the 1/f fluctuation, in which the power spectral density is inversely proportional to frequency, was confirmed. The 1/f fluctuation was considered to reflect the fractal-like structure of ultradian components of spontaneous locomotor activity. IP administration of 1.0 g/kg body weight of tetrachloroethylene at 0900 h produced a remarkable phase-shift (4.0 +/- 0.9 h) in the activity rhythm and an increase in the slope of fluctuation (0.4 +/- 0.1) in contrast to a relatively smaller decrease in the total amount of spontaneous locomotor activity. These behavioral effects of tetrachloroethylene were dose-dependently lower at lower doses. The present study demonstrated the usefulness of our systematic approach in evaluating the behavioral effects of chemical substances. PMID- 8459787 TI - The developmental consequences of low to moderate prenatal and postnatal lead exposure: intellectual attainment in the Cincinnati Lead Study Cohort following school entry. AB - In a further follow-up study of the Cincinnati Lead Study Cohort, 253 children were administered the Wechsler Intelligence Scale for Children-Revised (WISC-R) at approximately 6.5 years of age. Postnatal blood lead concentrations were inversely associated with Full-Scale (FSIQ) and Performance IQ (PIQ). Following statistical adjustment for developmental co-factors such as maternal IQ and an assessment of the quality of caretaking in the home environment, a statistically significant relationship remained between postnatal blood lead concentrations and PIQ. Further statistical analyses suggested that averaged lifetime blood lead concentrations in excess of 20 micrograms/dL were associated with deficits in PIQ on the order of approximately 7 points when compared to children with mean concentrations less or equal to 10 micrograms/dL. These results are discussed in terms of their consistency with other similar studies as well as their internal consistency with earlier reports on this cohort. The findings of this investigation support recent initiatives in the United States to reduce the exposure of children to environmental lead. PMID- 8459788 TI - Importance of experimenter-blind procedure in neurotoxicology. AB - The importance of having the investigator blind to the experimental condition of a human subject was demonstrated using meta analysis of 43 reports of the effects of carbon monoxide (CO) on behavior. It was shown that 75% of single-blind studies found significant CO effects as opposed to only 26% of double-blind studies (difference was significant, p < 0.005). It was also not possible to show that the difference could have been due to different CO exposure levels, different statistical practices, or different study group sizes. The failure to follow double-blind procedure has been partly responsible for disagreement about the effects of CO reported in the literature. Investigator blinding is also important in laboratory animal research. PMID- 8459789 TI - Brain aminopeptidase activity after subacute xylene exposure. AB - Xylene is a neurotoxic aromatic hydrocarbon widely used in industry. In this article, the effect of subacute xylene exposure on neutral and basic aminopeptidase activities in several regions of the rat brain is described. Neutral aminopeptidase activity only decreased significantly in the thalamus. There were no changes in basic aminopeptidase activity after the solvent administration. Thus, these brain aminopeptidase activities are largely unaffected by subacute exposure to xylene, which is not the case with benzene or carbon disulfide. This could be in line with its recognized lesser toxicity at the central nervous system level. PMID- 8459790 TI - Green tobacco sickness in tobacco harvesters--Kentucky, 1992. AB - Green tobacco sickness (GTS) is an illness resulting from dermal exposure to dissolved nicotine from wet tobacco leaves; it is characterized by nausea, vomiting, weakness, and dizziness and sometimes fluctuations in blood pressure or heart rate (1-3). On September 14, 1992, the Occupational Health Nurses in Agricultural Communities (OHNAC) project of Kentucky* received reports of 27 cases of GTS. The cases occurred among tobacco harvesters who had sought treatment in several hospital emergency departments in south-central Kentucky during the preceding 2 weeks. This report summarizes the findings of the investigation of these cases. PMID- 8459791 TI - Emergency mosquito control associated with Hurricane Andrew--Florida and Louisiana, 1992. AB - Hurricane Andrew crossed south Florida on August 24, 1992 entered the Gulf of Mexico, and struck the Louisiana coast on August 26. In Florida, an estimated 25,000 housing units were destroyed and 37,000 severely damaged in a 200,000-acre area in the southern portion of Dade County; in Louisiana, an estimated 25,000 housing units were destroyed or severely damaged by the storm, primarily in the coastal sections of the 36-parish disaster area. Initial assessment of the disaster areas indicated a need for vector surveillance and control (1). This report summarizes actions to assess and alleviate mosquito-related problems in Florida and Louisiana. PMID- 8459792 TI - Injuries and illnesses related to Hurricane Andrew--Louisiana, 1992. AB - On August 26, 1992, Hurricane Andrew struck Louisiana. On August 24, in anticipation of hurricane-related injuries and illnesses, the Office of Public Health (OPH), Louisiana Department of Health and Hospitals, in cooperation with hospital emergency room (ER) and public utility personnel and coroners, established an active emergency surveillance system in 19 parishes to monitor these events. This report summarizes the findings from this emergency surveillance system. PMID- 8459793 TI - Years of potential life lost before age 65--United States, 1990 and 1991. AB - Years of potential life lost (YPLL) is a public health measure that reflects the impact of deaths occurring in years preceding a conventional cut-off year of age, usually 65 years. YPLL is calculated using final mortality data from CDC's National Center for Health Statistics (1) for the most recent year available, provisional mortality data (i.e., a 10% sample of deaths) (2) for the following year, and population estimates from the U.S. Census. This report summarizes final YPLL data for 1990 and provisional data for 1991. PMID- 8459794 TI - Adult blood lead epidemiology and surveillance--United States, fourth quarter, 1992. PMID- 8459795 TI - Update: multistate outbreak of Escherichia coli O157:H7 infections from hamburgers--western United States, 1992-1993. AB - From November 15, 1992, through February 28, 1993, more than 500 laboratory confirmed infections with E. coli O157:H7 and four associated deaths occurred in four states--Washington, Idaho, California, and Nevada. This report summarizes the findings from an ongoing investigation that identified a multistate outbreak resulting from consumption of hamburgers from one restaurant chain. PMID- 8459796 TI - Use of smokeless tobacco among adults--United States, 1991. AB - Consumption of moist snuff and other smokeless tobacco products in the United States almost tripled from 1972 through 1991 (1). Long-term use of smokeless tobacco is associated with nicotine addiction and increased risk of oral cancer (2)--the incidence of which could increase if young persons who currently use smokeless tobacco continue to use these products frequently (1). To monitor trends in the prevalence of use of smokeless tobacco products, CDC's 1991 National Health Interview Survey-Health Promotion and Disease Prevention supplement (NHIS-HPDP) collected information on snuff and chewing tobacco use and smoking from a representative sample of the U.S. civilian, noninstitutionalized population aged > or = 18 years. This report summarizes findings from this survey. PMID- 8459797 TI - Gonorrhea--Colorado, 1985-1992. AB - The number of reported cases of gonorrhea in Colorado increased 19.9% from 1991 to 1992 after declining steadily during the 1980s. In comparison, in the United States, reported cases of gonorrhea in 1992 continued an overall decreasing trend (1). This report summarizes an analysis of the increase in gonorrhea in Colorado in 1992 and characterizes trends in the occurrence of this disease from 1985 through 1992. PMID- 8459798 TI - Impact of adult safety-belt use on restraint use among children < 11 years of age -selected states, 1988 and 1989. AB - Motor-vehicle crashes are the leading cause of death among children and young adults in the United States and account for more than 1 million years of potential life lost before age 65 annually (1). Child safety seats and safety belts can substantially reduce this loss (2). From 1977 through 1985, all 50 states passed legislation requiring the use of child safety seats or safety belts for children. Although these laws reduce injuries to young children by an estimated 8%-59% (3,4), motor-vehicle crash-related injuries remain a major cause of disability and death among U.S. children (1), while the use of occupant restraints among children decreases inversely with age (84% usage for those aged 0-4 years; 57%, aged 5-11 years; and 29%, aged 12-18 years) (5). In addition, parents who do not use safety belts themselves are less likely to use restraints for their children (6). To characterize the association between adult safety-belt use and adult-reported consistent use of occupant restraints for the youngest child aged < 11 years within a household, CDC analyzed data obtained from the Behavioral Risk Factor Surveillance System (BRFSS) during 1988 and 1989. This report summarizes the findings from this study. PMID- 8459799 TI - An allometric interpretation of the spatio-temporal organization of molecular and cellular processes. AB - Different levels of organization distinguished by characteristics spatial dimensions, Ec, and relaxation times, Tr, of biological processes ranging from electron transport in energy transduction to growth of microbial and plant cells, are shown to be related through a relation that may be interpreted as allometric and characterized by two different slopes. Processes, at levels of organization occurring in spatial dimensions of micrometers and relaxing in the order of minutes, delimit a 'transition point' between the two curves, that we interpret as a limit for the emergence of macroscopic coherence. The characteristic spatial dimension, Ec, and the relaxation time, Tr, contain dynamical information about the processes occurring at a given level of organization. When a steady state of a biological process at a certain level of organization becomes unstable, the system undergoes a transition to another level of organization. To exemplify the appearance of macroscopic order at levels of organization further from the 'transition point' we present in this report various experimental systems involving many levels of organization allometrically related that exhibit different kinds of self-organized behavior, i.e. bi-stability, oscillations, changes in (a)symmetry. PMID- 8459800 TI - Photoreactive fatty acid analogues that bind to the rat liver fatty-acid binding protein: 11-(5'-azido-salicylamido)-undecanoic acid derivatives. AB - Photoreactive probes for the hydrophobic pocket of the liver fatty acid-binding protein, 11-(5'-azido-salicylamido)-undecanoic acid (5' ASU) and its acetyl ester (Ac5' ASU), were synthesized and their interaction with the protein was assessed. Fatty acid-binding proteins are closely related proteins which are abundantly expressed in tissues with active lipid metabolism. A simple model that assumes that the protein possesses a single kind of sites fitted the binding of radioiodinated 5' ASU to L-FABP satisfactorily. The apparent dissociation constant, 1.34 x 10(-7) M, evidenced a slightly higher affinity than that reported for C16-C20 fatty acids. Consistent with the binding curve, 5' ASU effectively competed with palmitic acid for the hydrophobic sites and the effect was nearly complete for concentrations of 1 microM; oleic acid, in turn, displaced the radiolabelled probe. Irradiation at 366 nm of 125I-5' ASU bound to L-FABP caused the covalent cross-linking of the reagent. The amount of radioactivity covalently bound reached a maximum after 2 min thus agreeing with the photo-activation kinetics of the unlabelled compound that evidenced a t1/2 of 31.1 sec. The yield with which probes bound to L-FABP became covalently linked to the protein, appraised after SDS-PAGE of irradiated samples, was estimated as 23 and 26 per cent for 5' ASU and Ac5' ASU respectively. In turn, irradiation of L FABP incubated with 5' ASU or Ac5' ASU resulted in the irreversible loss of about one fourth its ability to bind palmitic acid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8459801 TI - Neoplastic association of enhanced type V collagen production in rat fibrosarcoma. AB - Collagens present in the connective tissues of the extracellular matrix of fibrosarcoma were isolated and characterized. The fibrosarcoma was induced in rats by the administration of 3-methylcholanthrene. The results obtained were compared with normal muscle. An excess amount of type V collagen was found to be produced by the fibrosarcoma tissue compared to the normal muscle. Type V collagen from fibrosarcoma was characterized on the basis of solubility behavior in sodium chloride solutions, electrophoretic mobility on SDS-polyacrylamide gels, elution pattern of phosphocellulose chromatography and amino acid composition. PMID- 8459802 TI - In vitro transcription of the c-myc first exon may be influenced by the extent of chromatin assembly. AB - The first exon of the human c-myc gene can be transcribed by either RNA polymerase II or RNA polymerase III. The molecular factors contributing to polymerase selection are not yet completely defined. We have examined the role of chromatin structure in regulating transcription by RNA polymerase III. Using as competitor a pol III gene in both a cis and trans arrangement, we demonstrate that c-myc gene expression is facilitated from templates containing a minimal number of fully assembled nucleosomes. The removal of excess histones by DNA titration leads to an elevated level of c-myc expression. These results suggest that either the c-myc expression is inhibited when the template is fully packaged into chromatin or that the affinity of RNA polymerase for the regulatory elements of this exon is such that a template, devoid of histones, is required for transcriptional initiation. PMID- 8459803 TI - Elevated levels of glycoprotein gp200 in progeria fibroblasts. AB - The glycosylation of proteins in fibroblasts from people with the premature ageing disease Hutchinson-Gilford Progeria Syndrome (progeria) was investigated. Protein was prepared from fibroblast cell lines established from skin biopsy taken from progeria patients and control donors. Glycoproteins were labelled by the covalent attachment of the steroid hapten digoxygenin to the sugar group. After separation of total protein by SDS-PAGE and electroblotting onto Immobilon PTM, glycoproteins were detected by enzyme immunoassay. We have observed a glycoprotein of M(r) 200 kDa which is consistently present in protein preparations from progeria fibroblasts and which is absent, or markedly reduced, in preparations from control fibroblasts. This suggests that it may be useful as a marker for progeria. Similar analysis of progeria lymphoblast and control lymphoblast cultures did not show this altered pattern of glycosylated proteins, indicating that it may be cell-type specific. Glycoproteins were also detected by labelling fibroblasts in vitro with D-[6-3H]glucosamine hydrochloride followed by SDS-PAGE of isolated protein and subsequent fluorography. Profiles of glycoproteins from progeria and control fibroblasts were consistent with those obtained from labelling of carbohydrate groups with digoxygenin. Protease digestion of cell protein verified that the band at M(r) 200 kDa contains a protein core. Characteristic features of progeria primarily involve the connective tissue and include wrinkled and loose skin, loss of soft tissue, thin limbs and stiff joints. Death of progeria patients is usually a result of cardiovascular abnormalities. The most consistent manifestations thus involve the connective tissue. The glycoprotein of M(r) 200 kDa which we have observed in progeria fibroblasts in vitro could reflect a perturbation in glycosylation which may underly the connective tissue defects seen in progeria. PMID- 8459804 TI - Regulation of brain 6-phosphofructo-1-kinase: effects of aging, fructose-2,6 bisphosphate, and regional subunit distribution. AB - Total 6-phosphofructo-1-kinase (PFK) activity, amounts of each type of PFK subunit, and levels of fructose-2,6-P2 in the cerebral cortex, midbrain, pons medulla, and cerebellum of 3, 12, and 25 month rats were measured. Further, the role of fructose-2,6-P2 in the regulation of brain PFK activity was examined. A positive correlation was found to exist between the reported losses of glucose utilization as measured by 2-deoxy-D-glucose uptake and PFK activity in each region. That is, both parameters decreased to their lowest level by 12 months of age and remained decreased and fairly constant thereafter. Fructose-2,6-P2 levels did not appear to directly correlate with regional changes in glucose utilization. Also, region-specific and age-related alterations of the PFK subunits were found although these changes apparently did not correlate with decreased glucose utilization. Brain PFK is apparently saturated with fructose 2,6-P2 due to the high endogenous levels, and it contains a large proportion of the C-type subunit which dampens catalytic efficiency. Consequently, brain PFK could exist in a conformational state such that it can readily consume fructose-6 P rather than in an inhibited state requiring activation. This may explain, in part, the ability of brain to efficiently but conservatively utilize available glucose in energy production. PMID- 8459805 TI - Molecular cloning and characterization of the human E-cadherin cDNA. AB - E-cadherin is a Ca(2+)-dependent cell adhesion molecule involved in cell-cell interaction. In its normal physiological function it plays an important role in embryonic development and tissue morphogenesis. Recent studies have shown that in cancer development E-cadherin can act as a suppressor of invasion. Indeed, in several kinds of carcinomas allelic loss of the E-cadherin/Uvomorulin locus and decreased E-cadherin expression have been described. The importance of E-cadherin in human cancer development may be substantiated by molecular analysis of the E cadherin transcript. Therefore, we isolated and characterized the human E cadherin cDNA. Comparison of the nucleotide and deduced amino acid sequences revealed that the human E-cadherin is highly homologous to the mouse E-cadherin (uvomorulin) and to other members of the cadherin family. PMID- 8459807 TI - Characterization of anti-crystallin autoantibodies in patients with cataract. AB - Anti-crystallin autoantibodies have often been demonstrated in the serum of healthy persons and, especially, patients with cataract. In no case, however, have the specific crystallin subunits been identified against which such antibodies are directed. This information would be of particular interest in view of the recent finding that several crystallin subunits occur constitutively outside the lens. To fill this gap, we analysed the sera of 15 patients with mature cataract by means of 1- and 2-dimensional immunoblotting. The circulating antibodies turned out to be directed against several beta- and gamma-crystallin subunits. The types of subunits and the intensities of the responses varied considerably between patients. No or only occasional and very weak reactions were observed against the alpha A-, alpha B- and beta B2-crystallin subunits. These are in fact the only crystallins at present known to occur outside the lens in mammals. Our findings thus indicate that anti-crystallin autoantibodies are specifically directed against those crystallins that appear to be lens restricted, while immunological tolerance would exist for the extra-lenticularly occurring crystallins. PMID- 8459806 TI - Psoralen crosslinking of small RNAs in vitro. PMID- 8459809 TI - [An unusual course of hereditary photodermatosis: De-Sanctis-Caccione syndrome?]. AB - We report about an unusual development of a hereditary photodermatosis in an almost 11-year-old girl. At the age of 11 months the first symptom was a profuse solar inflammation of the skin. By the beginning of the third year neurological symptoms appeared with an ataxic gait, dysarthria, areflexia, asynchronism and bilateral pes cavus. All findings in the following progress demonstrated an intense progression with an intermittent aggravation during summer. Analysis of chromosomes revealed a high number of chromosomal breaks and a high SCE rate (sister chromatid exchange). Finally we diagnosed a De-Sanctis-Cacchione syndrome. PMID- 8459808 TI - [Congenital adrenal cortex hypoplasia. The diagnostic importance of estriol determination in late pregnancy]. AB - Congenital adrenocortical hypoplasia is a malformation of unknown etiology leading to Addison's disease. The prognosis depends on early diagnosis which is difficult during the neonatal period. Decreased maternal secretion of estriol in late pregnancy is an important diagnostic clue. PMID- 8459810 TI - [Seizures and hyponatremia in a newborn infant]. AB - A three days old mature female newborn presented with seizures. The diagnostic data revealed a hyponatraemia (113 mmol/l) as pathogenic origin. Further causes of convulsions could be excluded. Administering saline solution (0.9%) intravenously the plasma sodium level reached normal ranges within 36 hours. We propose that an excessive enteral administration of glucose solution during the first three days of life must have led to dilutional hyponatraemia. This suggestion is in accordance with observations in older children presenting with similar symptoms. PMID- 8459811 TI - [Secondary myocardial hypertrophy in a very small premature infant treated with dexamethasone]. AB - BACKGROUND: There is an increasing number of reports about the use of dexamethasone in the treatment of preterm infants at high risk for bronchopulmonary dysplasia. The possibility of myocardial hypertrophy developing during this treatment has not been examined. METHODS: As an example the course of one patient is described. We examined seven preterm infants (mean birth weight 791 g, mean gestational age 26 weeks) with eight treatments of dexamethasone retrospectively. The therapy was associated with a significant increase of the mean thickness of the interventricular septum and of the left ventricular posterior wall. After the termination of dexamethasone therapy the abnormal echocardiographic findings disappeared. CONCLUSION: We suggest careful monitoring of preterm infants treated with dexamethasone by performing serial echocardiographic investigations. PMID- 8459812 TI - [Post-conceptional age. Effect on protein requirements of premature infants]. AB - In 12 preterm infants (mean gestational age: 28.9 weeks; mean birthweight: 1230 g) (Group 1) the serum concentrations of urea and alpha-amino-nitrogen were studied during the 32nd and between the 36th and 37th week of post-conceptional age. In 9 preterm infants with a mean gestational age of 34.6 weeks (mean birthweight: 1860 g) (Group 2) the same parameters were estimated during the 36th or 37th week of postconceptional age. In all male infants (group 1: n = 6; group 2: n = 5) the excretion of nitrogen in urine and stools were measured during a 48 h balance period. During the study all infants were fed with human milk enriched with 3 g of a bovine human milk fortifier (Eoprotin, Milupa AG, Germany) per 100 ml human milk (mean protein intake: 3.4 g/kg.day; mean caloric intake: 132.5 kcal/kg.day). Despite the similar protein and energy intakes on all study days the serum concentrations of urea and alpha-amino-nitrogen were significantly higher during the 36th or 37th postconceptional week if compared to those found during the 32nd postconceptional week. This was accompanied by elevated renal excretion of total nitrogen due to an increased excretion of urea in the older infants. The nitrogen excretions in stools were low during both study periods. During the period 36 and 37 weeks of postconceptional age no differences could be found for all parameters studied between the both groups of different gestational ages. The data of the present study suggest that in preterm infants with postconceptional age of 37 weeks or more protein intakes of 3.4 g/kg.day and more may exceed the requirements of these infants. Thus, supplementation of human milk with protein is not necessary after the 37th week of postconceptional age if feeding volumes of 170 ml/kg.day or more are tolerated. PMID- 8459813 TI - [Sleep apnea in hyperplasia of the pharyngeal lymphatic tissue. Polysomnographic studies in children]. AB - BACKGROUND: Hyperplasia of tonsils and adenoids is a common finding in early childhood. Breathing difficulties caused by hyperplastic lymphatic tissue represent an indication for adenoidectomy and tonsillectomy. It was examined, whether a polysomnographic recording is a useful tool to assess the severity of obstructive sleep apnea in children with hyperplasia of tonsils and adenoids. METHODS: In 15 patients (10 boys, 5 girls), 1.0 to 6.6 years of age, with a history of breathing difficulties during sleep a thorough clinical evaluation was performed. Additionally, a polysomnographic recording was carried out, including thoracic and abdominal breathing movements, nasal and buccal thermistor, ECG and transcutaneous blood gases. RESULTS: Before therapy, severe obstructive apnea was demonstrated by polysomnography in all patients. This finding disappeared almost completely after surgery. Hyperplasia of adenoids was diagnosed in 3 patients, hyperplasia of tonsils in 3 patients, hyperplasia of tonsils and adenoids in 8 patients, and other kind of lymphatic hyperplasia in 1 patient. CONCLUSION: Hyperplasia of tonsils and adenoids contributes to the development of sleep-apnea syndrome in childhood. A polysomnographic recording seems to be a useful tool to describe the severity of obstructive sleep apnea in children with hyperplasia of tonsils and adenoids. PMID- 8459814 TI - [Cryptosporidium enteritis]. AB - Cryptosporidium has been found to be a common cause of gastroenteritis during the last years. The natural course of the disease in immunocompromised patients is often met by serious complications. A general therapy recommendation has not been reported so far. We report of a two-year-old boy, who was immunocompromised by a multidrug cytostatic chemotherapy. The patient suffered from a long lasting most severe gastroenteritis, caused by cryptosporidium. There was a good clinical response to spiramycin, a treatment suggested in the literature. PMID- 8459815 TI - [Unusual symptoms in brain tumors in childhood]. AB - Headache, nausea, ataxia and diplopia are leading symptoms of brain tumors in children. We report of 3 children with unusual symptoms and findings. Patient 1 complained of occasional headaches. Clinical examination showed neurological deficits and uveitis. Lumbar puncture revealed a pleocytosis and the oligoclonal banding study was positive. Cranial MRI demonstrated an enlarged pons. Under treatment with cortisone a clinical improvement was seen, but no change of the abnormalities in MRI. Several weeks later a biopsy was performed, which verified an astrozytoma. The second child developed a torticollis, following an accident, and later a refractory constipation was noted. A clinical evaluation was within normal limits. Several weeks later the patient complained of bladder disturbances. Patient 3 had a lateralized tic disorder without any neurologic deficits. CT showed an infratentorial tumor above the 4th ventricle. The tic disorder vanished only after the tumor was completely resected in the second operation. The reported cases demonstrate the fact that in an individual patient a brain tumor can cause unusual symptoms and findings which do not make the diagnosis obvious. PMID- 8459816 TI - [Blood coagulation disorders in childhood]. PMID- 8459817 TI - [Pertussis illnesses increase the reactivity of the bronchial system]. PMID- 8459818 TI - [Opening of the 88th annual congress of the German Society of Pediatrics 20 September 1992 in Hamburg. Opening address of the president]. PMID- 8459819 TI - [Pediatrics in the decade of neurosciences. Opening address]. PMID- 8459821 TI - [Epilepsies with absence in childhood]. AB - Absences are one of the most often seen type of seizures in the first and second decade and the prominent feature in infantile, juvenile and childhood absence epilepsy. Besides these in some way benign epilepsies absences were found in other prognostic more serious epileptic syndromes and in some neurodegenerative diseases. Therefore, the appearance of absences in the pediatric age group need a thoroughly done work up in any patient. PMID- 8459820 TI - [Epilepsies with complex focal seizures in childhood. Seizure semiology and routine EEG, localization, neuropathology and etiology, follow-up forms and prognosis with anticonvulsant therapy]. AB - Focal epilepsies of childhood with complex partial seizures, with or without secondarily generalized seizures are reviewed. Particular emphasis is placed on the semiology of seizures, which are subdivided into: aura, disturbance of consciousness, speech disturbances, automatims, and other motor and vegetative seizure symptoms. The significance of routine ictal and interictal EGGs and their importance for the localization is discussed. Recent neuropathological findings and etiology are presented and the courses epilepsies can take (especially those involving febrile convulsions), prognosis and long-term therapy with standard antieleptic drugs. A definition of pharmacoresistance is given, a prerequisite for surgical therapy, which in turn necissitates special presurgical diagnostic procedures [corrected]. PMID- 8459822 TI - A 40-kilobase subtelomeric region is common to most Plasmodium falciparum 3D7 chromosomes. AB - Starting from previous evidence indicating that some features are shared by several Plasmodium falciparum chromosomal extremities, a subtelomeric region present on most P. falciparum 3D7 chromosomes has been mapped. It was shown to occupy about 40 kb, and to include the proximal portion of pPftel. 1, the only telomeric clone described for P. falciparum [12], the complete 21-bp repetitive cluster and some conserved sites (PstI, EcoRI) proximally located with respect to this cluster. PMID- 8459823 TI - Expression of lipophosphoglycan, high-molecular weight phosphoglycan and glycoprotein 63 in promastigotes and amastigotes of Leishmania mexicana. AB - The abundant surface glycoconjugate of Leishmania promastigotes, lipophosphoglycan (LPG), forms a blue-colored complex (lambda max = 649 nm) with the cationic dye Stains-all, which can be quantitated densitometrically on polyacrylamide gels of cell lysates. Promastigotes of Leishmania mexicana, Leishmania major and Leishmania donovani yield values of 1-3 x 10(6) LPG molecules cell-1. In amastigotes the LPG content is down-regulated below the detection limit (< 10(3) molecules cell-1) in L. mexicana and L. donovani, but remains significant in L. major (2 x 10(3) molecules cell-1). In the case of L. mexicana, these results are supported by immunological studies. Using several monoclonal and polyclonal antibodies, LPG is undetectable by immunoblotting in lysates of either amastigotes or infected macrophages and the amastigote surface is devoid of LPG as judged by immunofluorescence and immunoelectron microscopy. Immunoblotting experiments demonstrate that amastigotes synthesize hydrophilic high-molecular weight compounds which stain blue with Stains-all and cross-react with the monoclonal and polyvalent antibodies suggesting the presence of similar phosphoglycan structures as in LPG. The high-molecular weight phosphoglycan appears to be located in the lumen of the flagellar pocket of mouse lesion amastigotes and may be secreted from there into the lumen of the parasitophorous vacuole of parasitized macrophages. In L. mexicana promastigotes the surface protease gp63 is amphiphilic and comprises about 1% of the cellular proteins. In contrast, in amastigotes gp63-related proteins are predominantly hydrophilic; they amount to only about 0.1% of the cellular proteins and are mainly located in the lumen of the extended lysosomes (megasomes) characteristic for this species. PMID- 8459824 TI - Uptake and metabolism of S-adenosyl-L-methionine by Leishmania mexicana and Leishmania braziliensis promastigotes. AB - Promastigotes of Leishmania mexicana and Leishmania braziliensis incorporate S adenosyl-L-[3H-methyl]methionine (AdoMet) against a concentration gradient through a saturable system. This concentrative uptake requires metabolic energy and is sensitive to temperature and sulfhydryl reagents such as N-ethyl maleimide. Intracellular AdoMet exchanges with external AdoMet. At steady state, unaltered ADoMet in the intracellular pool is at about a 1800-fold concentration in relation to that found in the external medium. Glucose, galactose and ribose did not stimulate uptake rates. Incorporated AdoMet goes into the soluble AdoMet pool, where a small fraction is metabolized, chiefly into methylthioadenosine, decarboxylated AdoMet and methanol. After a 60 min pulse the radioactivity associated with the [3H]AdoMet incorporated disappears with a half-time of 2 h. Transmethylation reactions were analyzed following [3H]AdoMet incorporation. Fractionation experiments indicate that 45-62% and 30-42% of the radioactivity is incorporated into lipids and protein methyl esters respectively, with 5-14% present in the soluble pool of parasites. Sinefungin or its cyclic derivative (1 and 10 micrograms ml-1) in the incubation medium produces 58% and 64% inhibition of AdoMet incorporation into Leishmania promastigotes. Most transmethylation reactions are inhibited, as there is a 50% decrease in the total radioactivity present in both the base-labile and lipidic fraction, with a parallel increase in the percentage of radioactivity in the soluble pool. Previous results give evidence of the importance of AdoMet in American Leishmania promastigote metabolism. PMID- 8459825 TI - Selective inhibition of Plasmodium falciparum aldolase by a tubulin derived peptide and identification of the binding site. AB - Aldolase of the human malaria parasite Plasmodium falciparum (PfAldo) may be a potential target for the development of novel antimalarial drugs. Using in vitro mutagenesis we analyzed the function of the carboxy-terminus of the recombinant enzyme. Deletion of the carboxy-terminus of PfAldo confirmed its critical role in catalysis; exchange of conserved residues minimally affected enzyme activity. We exchanged a pair of parasite specific lysine residues with corresponding amino acids of the host. These mutant enzymes exhibited an increased catalytic activity and reduced binding to erythrocyte band 3 protein. Homologous peptides of human band 3 protein and P. falciparum alpha-tubulin were competitive inhibitors of PfAldo. Selective inhibition of PfAldo by the alpha-tubulin peptide depends on the presence of tandem lysine residues and the fine structure of the inhibitor peptide. Our data support the concept of a matrix organisation of glycolytic enzymes in Plasmodium falciparum. PMID- 8459826 TI - Conservation of primary sequence of gp29, the major soluble cuticular glycoprotein, in three species of lymphatic filariae. PMID- 8459827 TI - Cloning and sequencing of a complete myosin heavy chain cDNA from Schistosoma mansoni. PMID- 8459828 TI - DNA diagnosis of falciparum malaria using a double PCR technique: a field trial in the Solomon Islands. PMID- 8459829 TI - Cloning of a cDNA encoding an egg antigen homologue from Schistosoma mansoni. PMID- 8459830 TI - Peptide-fluoromethyl ketones arrest intracellular replication and intercellular transmission of Trypanosoma cruzi. AB - The major proteolytic activity of Trypanosoma cruzi is a cathepsin L-like cysteine protease expressed in all stages of the parasite. As an initial step in identifying possible functions of this enzyme in the life cycle of T. cruzi, and examining its potential as a target for rational drug design, two fluoromethyl ketone-derivatized cysteine protease inhibitors were studied for their effects on T. cruzi infection of mammalian cells. Both inhibitors are irreversible substrate analogues with high specificity for cysteine proteases and minimal toxicity to mammalian cells. While micromolar concentrations of inhibitors had some effect on replication of all parasite stages, the most dramatic arrest of parasite replication occurred at the transformation of trypomastigote to amastigote, and also from amastigote to trypomastigote. It is therefore proposed that the enzyme functions in intracellular protein degradation in some stages of T. cruzi, but also in remodeling of the parasite during transformation between stages. Concentrations of inhibitors necessary to interrupt the parasite life cycle had no observable toxicity to macrophages, fibroblasts or epithelial cells in culture. Differential susceptibility of T. cruzi versus host cysteine proteases to fluoromethyl ketone protease inhibitors suggests that inhibition of the T. cruzi cysteine protease is a potential lead for new chemotherapy of Chagas' disease. PMID- 8459831 TI - Characterization of the Onchocerca volvulus superoxide dismutase gene and mRNA processing. PMID- 8459832 TI - Molecular cloning of a rho family gene of Entamoeba histolytica. AB - An Entamoeba histolytica gene (Eh rho1) was cloned that encodes a putative low molecular-mass GTP-binding protein, most similar to the ras homologue rho. The Eh rho1 open reading frame was 208 amino acids long and encoded a 23-kDa protein similar to Saccharomyces cerevisiae RHO1-RHO4 and CDC42 and human rhoA, rac1, and G25K gene products. This similarity was greatest at the NH2 terminus of Eh rho1 where two GTP-binding sites and a possible effector site were conserved. A cysteine residue at the COOH terminus of Eh rho1 was followed by eight hydrophobic amino acids rather than the three hydrophobic amino acids present in other ras family proteins. PMID- 8459833 TI - Inter- and intra-species differentiation of trypanosomes by genomic fingerprinting with arbitrary primers. PMID- 8459834 TI - Structural features of Plasmodium cytochrome b that may underlie susceptibility to 8-aminoquinolines and hydroxynaphthoquinones. AB - Appropriate functioning of mitochondria is critical for survival and growth of erythrocytic stages of malarial parasites, making it an attractive target for antimalarial drugs which may take advantage of unique features of parasite mitochondrial metabolism. We have sequenced the presumptive mitochondrial DNA, the 6-kb element, of Plasmodium falciparum, permitting an analysis of the predicted structure of parasite electron transport proteins. Although the overall structures of the 3 polypeptides, cytochrome c oxidase subunit 1, cytochrome c oxidase subunit 3, and cytochrome b (cyt b), were similar to those from other species, some striking differences were observed, especially for the cyt b. Analysis of the cyt b structure showed that the critical quinone binding sites of the protein are quite divergent from those of other species. Comparative analysis suggests that these changes are the likely cause for the resistance of parasite cytochrome bc1 complex to antimycin and related inhibitors. We suggest that the same features are responsible for increased affinity of the parasite cyt b for antimalarial compounds of class 8-aminoquinolines and hydroxynaphthoquinones, explaining the therapeutic value of these drugs. PMID- 8459835 TI - Rates of amino acid evolution in the 26- and 28-kDa glutathione S-transferases of Schistosoma. AB - Statistical analysis of glutathione S-transferase (GST) sequences of Schistosoma mansoni, Schistosoma japonicum, and other animals revealed that, in comparison both to the related mammalian alpha GSTs and to Schistosoma 26-kDa GSTs, the 28 kDa GSTs of Schistosoma have evolved unusually rapidly at the amino acid level in the ordinarily conserved N-terminal portion of the molecule. Because this rapid rate of evolution is reflected at the amino acid level and at nonsynonymous nucleotide sites but not at synonymous nucleotide sites, it must be due to a relaxation of functional constraint on the N-terminal region of the Schistosoma 28-kDa GSTs rather than to a high mutation rate. By contrast, the 26-kDa GSTs of Schistosoma not only show a slower rate of amino acid evolution in the N-terminal portion than the 28-kDa GSTs but also have evolved more slowly in the C-terminal portion than have the related mammalian mu GSTs. The two 26-kDa GSTs of S. mansoni show particularly strong amino acid conservation between one another in the N-terminal region and a predominance of conservative amino acid replacements. PMID- 8459836 TI - Characterization of a Trypanosoma brucei nuclear gene encoding a protein homologous to a subunit of bovine NADH:ubiquinone oxidoreductase (complex I). AB - A Trypanosoma brucei gene has been identified that encodes a protein predicted to be a component of the trypanosome homologue of mitochondrial NADH:ubiquinone oxidoreductase (complex I). High homology was found to a 20-kDa component of the iron-sulfur protein fraction of bovine mitochondrial NADH:ubiquinone oxidoreductase and the products of the ndhK locus of Paramecium tetraurelia mitochondria and the NQO6 locus of Paracoccus denitrificans. The homology extends to several other proteins predicted to function as part of electron transport systems, including the psbG/ndhK gene products of chloroplast and cyanobacterial genomes which are thought to be subunits of a NADH:plastoquinone oxidoreductase involved in chlororespiration. The T. brucei ndhK counterpart is nuclearly encoded. An extended amino terminus of the T. brucei ndhK with structural similarity to mitochondrial presequences indicates that its transfer into mitochondria is likely. Stumpy and slender bloodforms and procyclic forms all possess similar levels of ndhK transcripts despite previous reports of stage regulated expression of complex I-like activity. PMID- 8459837 TI - A repetitive protein from Trypanosoma brucei which caps the microtubules at the posterior end of the cytoskeleton. AB - The major structural component of the cyto-architecture of Trypanosoma brucei is a microtubular array which envelopes the entire cell body and which is in close contact with the overlying cell membrane. A cytoskeletal protein has been identified which is associated with the microtubules of this array at their posterior ends exclusively. This protein, Gb4, is coded for by a very large gene which consists of numerous, tandemly linked repeat units of 0.6 kb length. Despite the large size of the gene, and also of the corresponding mRNA, the mature Gb4 protein has a size of only 28 kDa. Gb4 is well conserved between different species of African trypanosomes. PMID- 8459838 TI - Molecular species analysis of phospholipids from Trypanosoma brucei bloodstream and procyclic forms. AB - We present a quantitative description of the molecular species composition of the major phospholipid classes in bloodstream and procyclic forms of Trypanosoma brucei. Phospholipid classes were resolved by 2-dimensional thin-layer chromatography. Diradylglycerols were released from individual phospholipid classes by phospholipases C, converted into benzoate derivatives and separated into diacyl, alkylacyl and alk-1-enylacyl subclasses. Individual molecular species were quantitated and identified by HPLC and the assignments were confirmed by mass spectrometry. Comparison of the diacyl species of PC, PE and PI in bloodstream trypanosomes showed major differences in the relative amounts of individual molecular species between the different classes but not striking changes in the degree of saturation or overall chain length. In contrast, in procyclic trypanosomes the relative amounts of diacyl molecular species with polyunsaturated fatty acyl chains decreased in the order of PC > PE >> PI. Also, the alkylacyl and alk-1-enylacyl subclasses of PC and PE in bloodstream trypanosomes comprised a single molecular species, 18:0 18:2. Such exclusivity was not observed in procyclic trypanosomes among the same phospholipid subclasses, although 18:0 18:2 was the predominant species. Almost all the PI of bloodstream forms contained one 18:0 acyl species, which is consistent with the composition of the PI used for glycosylphosphatidylinositol synthesis. PMID- 8459839 TI - Amgen to spend $80 million to create Canadian institute. PMID- 8459840 TI - Terms of Scripps-Sandoz agreement may be more common than its critics believe. PMID- 8459841 TI - EMBL selects Cambridge as site for new database. PMID- 8459842 TI - Kafatos to be EMBL director; promises greater opportunity. PMID- 8459843 TI - Amersham to pay 50 million pounds for US Biochemical. PMID- 8459844 TI - Canada decides, at last, to increase spending on AIDS. PMID- 8459845 TI - The cost of surrogacy. PMID- 8459846 TI - Why microtubules grow and shrink. PMID- 8459847 TI - Microbiology. Giants among the prokaryotes. PMID- 8459848 TI - Cannibals among the Neanderthals? PMID- 8459849 TI - The largest bacterium. AB - The large, morphologically peculiar microorganism Epulopiscium fishelsoni inhabits the intestinal tract of Acanthurus nigrofuscus, a brown surgeonfish (family Acanthuridae) from the Red Sea. Similar microorganisms have been found in surgeonfish species from the Great Barrier Reef. As these microorganisms have only been seen in surgeonfish and no free-living forms have been found, they are considered to be specific symbionts of surgeonfish, although the nature of the symbiosis is unclear. Initial reports considered them to be eukaryotic protists, based primarily on their size, with individuals being larger than 600 microns by 80 microns. But their cellular morphology in the electron microscope is more like that of bacterial than eukaryotic cells. To resolve the nature of these symbionts, we have isolated the genes encoding the small subunit ribosomal RNA from two morphotypes and used them in a phylogenetic analysis. In situ hybridization with oligonucleotide probes based on the cloned rRNA sequences confirmed the source of the rRNA genes. Our result identify the symbionts as members of the low-(G+C) Gram-positive group of bacteria. They are therefore the largest bacteria to be described so far. PMID- 8459850 TI - Germ-line transmission and expression of a human-derived yeast artificial chromosome. AB - Introduction of DNA fragments, hundreds of kilobases in size, into mouse embryonic stem (ES) cells would greatly advance the ability to manipulate the mouse genome. Mice generated from such modified cells would permit investigation of the function and expression of very large or crudely mapped genes. Large DNA molecules cloned into yeast artificial chromosomes (YACs) are stable and genetically manipulable within yeast, suggesting yeast-cell fusion as an ideal method for transferring large DNA segments into mammalian cells. Introduction of YACs into different cell types by this technique has been reported; however, the incorporation of yeast DNA along with the YAC has raised doubts as to whether ES cells, modified in this way, would be able to recolonize the mouse germ line. Here we provide, to our knowledge, the first demonstration of germ-line transmission and expression of a large human DNA fragment, introduced into ES cells by fusion with yeast spheroplasts. Proper development was not impaired by the cointegration of a large portion of the yeast genome with the YAC. PMID- 8459851 TI - A yeast artificial chromosome covering the tyrosinase gene confers copy number dependent expression in transgenic mice. AB - Expression of transgenes in mice often fails to follow the normal temporal and spatial pattern and to reach the same level as the endogenous copies. Only in exceptional cases has position-independent and copy number-dependent expression been reproduced. The size constraint of standard constructs may prevent the inclusion of important remote regulatory elements. Yeast artificial chromosomes (YACs) provide a means of cloning large DNA fragments and the transfer of YAC DNA into somatic cells has been reported. We have previously produced transgenic mice carrying a 35 kilobase YAC construct. Here we report the transfer of a 250 kilobase YAC covering the mouse tyrosinase gene into mice by pronuclear injection of gel-purified YAC DNA. The YAC was inserted into the mouse genome without major rearrangements and expression of the YAC-borne tyrosinase gene resulted in complete rescue of the albino phenotype of the recipient mice. Expression from the transgene reached levels comparable to that of the endogenous gene and showed copy number dependence and position independence. PMID- 8459852 TI - Thermodynamic beta-sheet propensities measured using a zinc-finger host peptide. AB - The three-dimensional structures of proteins reveal that the distribution of amino acids within the major classes of secondary structure is not random but that each amino acid has its own preferred secondary structural arrangements. Propensity scales for residues in alpha-helices have been generated through the use of various host-guest systems. Here we measure the thermodynamic beta-sheet propensities of each of the twenty commonly occurring amino acids. A previously studied zinc-finger peptide was used as the host system in which amino acids were substituted into a guest site, a solvent-exposed position in an antiparallel beta sheet. As these peptides are unfolded in the absence of bound metal but are folded in their presence, it is assumed that the thermodynamics of metal binding fully reflect peptide-folding energy. A competitive cobalt(II)-binding assay was used to determine these energies with high precision. The relative free energies correlate well with previously derived potential values based on statistical analysis of protein structures. We are therefore able to present a thermodynamic beta-sheet propensity scale for all the commonly occurring amino acids in aqueous solution. PMID- 8459853 TI - [Nocardiosis: a treacherous generalized infection]. PMID- 8459854 TI - [Is there a relationship between fatal myocardial infarct and the use of psychotropic drugs in young women?]. PMID- 8459855 TI - [Diagnosis and chemoprophylaxis of perinatal infections caused by beta-hemolytic streptococci from Group B]. PMID- 8459856 TI - [Central spinal cord syndrome]. PMID- 8459857 TI - [Duplicate publications: a miraculous multiplication]. PMID- 8459858 TI - [Duplicate publication of original manuscripts in and from the Nederlands Tijdschrift voor Geneeskunde]. AB - OBJECTIVE: To determine the numbers of correct (meeting the Vancouver rules) and incorrect duplicate publications of original articles (OA) in the Ned Tijdschr Geneeskd. DESIGN: Retrospective bibliometric study followed by interviews. SETTING: The journal's editorial office. METHOD: Of the first and second author of 172 OA (all 95 OA from the first half of 1990 and all 77 OA from the first half of 1992) all biomedical publications of the same purport published in 1990 1992 were looked up. Subsequently the authors were approached by telephone to find out the background of these duplicate publications. RESULTS: Of 2 OA the corresponding articles were not found. Of the remaining 94 OA from the first half of 1990, II (12%) proved to have been published again without this fact being mentioned in a footnote as required by the rules (for which omission the journals were responsible in 4 and the authors in 7 cases). Of the remaining 76 OA from the first half of 1992, 12 were found to have been published previously, 5 in accordance with and 7 (9%) against the rules. Duplicate publication against the rules was to be attributed to incorrect interpretation of the Vancouver rules by the authors. CONCLUSION: Of the OA in the Ned Tijdschr Geneeskd a minimum of 14% are or have already been published elsewhere, 11% without this fact being stated as required by the Vancouver rules. PMID- 8459859 TI - [The return of severe infections caused by Streptococcus pyogenes]. AB - Two patients with severe group A streptococcal infection associated with a toxic shock-like syndrome are described. Both isolates produced the pyrogenic exotoxin B. Since 1987 there have been many reports of these severe streptococcal infections. In order to know the incidence in the Netherlands, isolates from patients with severe streptococcal infection have to be serotyped (types of M protein) and tested for streptococcal toxin production, and serum antibody levels have to be determined. PMID- 8459860 TI - [Necrotizing fasciitis caused by Group A beta-hemolytic streptococci]. AB - A case is presented of a 35-year-old man with necrotizing fasciitis caused by group A beta-haemolytic Streptococci, accompanied by severe systemic toxicity, and necessitating amputation of the leg. After prolonged intensive care treatment the patient recovered. PMID- 8459861 TI - [Puerperal toxic shock syndrome caused by Group A beta-hemolytic streptococci]. AB - This case report describes the history of a young female with a streptococcal toxic shock syndrome secondary to a puerperal sepsis. The syndrome was complicated by severe hypotension, reversible kidney dysfunction, adult respiratory distress syndrome, coagulation disturbances, myositis and rhabdomyolysis. This latter complication required amputation of both lower legs. PMID- 8459862 TI - [The dissertation: a sacred cow, or discovered as a scientific (duplicate) publication?]. PMID- 8459863 TI - [Erroneously prepared oral rehydration solution is life-threatening]. PMID- 8459864 TI - [Computerized tomography following arthrography in instability of the shoulder joint]. PMID- 8459865 TI - [Loss of taste during administration of terbinafine]. PMID- 8459866 TI - [HA-1A anti-endotoxin antibody]. PMID- 8459867 TI - [Loss of taste during administration of terbanifine]. PMID- 8459868 TI - [Risk of hemorrhage with administration of fluoxetine (Prozac) or fluvoxamine (Fevarin)]. PMID- 8459869 TI - Long-term results of renal transplantation in children. PMID- 8459870 TI - Successful control of hyperparathyroidism in patients on continuous ambulatory peritoneal dialysis using magnesium carbonate and calcium carbonate as phosphate binders. AB - To avoid the use of aluminium as a phosphate binder, patients on CAPD who were stable were dialysed against a peritoneal dialysis fluid which was magnesium free. A mixture of calcium and magnesium carbonate was used as a phosphate binder over a period in excess of 1 year. Vitamin D analogues were used in the majority. Results show satisfactory control of hyperparathyroidism with mean parathyroid hormone concentration for the group of 121 pg/ml (normal < 100 pg/ml), calcium concentration of 2.41 mmol/l, magnesium 0.97 mmol/l, phosphate 1.36 mmol/l and aluminium 0.35 mmol/l (normal < 0.2 mumol/l). These results were as good as and better in some respects than a minority using calcium carbonate alone or remaining on aluminium hydroxide, the latter remaining on Mg-containing CAPD fluid. PMID- 8459871 TI - Parathyroidectomy and blood pressure in hemodialysis patients. AB - To assess whether parathyroidectomy (PTx) affects blood pressure (BP) in hemodialysis (HD) patients, we studied 11 uremics on HD treatment for 8.2 +/- 0.9 years who underwent successful PTx. As the control group, we selected 11 HD patients not submitted to PTx, matched with the study group for sex, age, years on HD, dialysis procedure and BP values. In the controls, BP and body weight did not change during the 2 years of observation. In the patients, BP remained stable in the year before PTx. PTx caused a progressive reduction in BP in 7 of the 11 patients. The fall was significant from the 3rd quarter onward (mean BP values before PTx: 139/82 mm Hg, 1 year after PTx: 122/75 mm Hg). The magnitude of the hypotensive effect of PTx was related to the pre-PTx systolic BP value (r = 0.70, p = 0.016). PTx also caused a significant progressive increase in body weight (1.56 +/- 0.57 kg 1 year after PTx). In conclusion, PTx causes BP fall in HD patients regardless of whether their preintervention values are normal or increased. The BP reduction occurs in concomitance with a consistent increase in body weight. BP variations are clinically relevant and may be related to the post PTx calcium efflux from the vessel wall. PMID- 8459872 TI - Effect of clomiphene citrate on hormonal profile in male hemodialysis and kidney transplant patients. AB - The aim of this study was to evaluate the role of clomiphene citrate (CC) therapy in the hypothalamus-pituitary-gonadal axis of male uremic subjects. Thirty-four patients on hemodialysis (HD) and 8 successful kidney transplant subjects (RT) were evaluated. Nine healthy males were used as controls (C). At baseline, zinc, testosterone (TEST), prolactin (PRL), FSH, LH and estradiol plasma concentrations were measured. All subjects were treated with CC (100 mg/day) for a week. The aforementioned parameters were determined again on the seventh day of CC therapy, and 3 days after drug withdrawal. Following CC, there was a rise in FSH, LH and TEST levels in all subjects (p < 0.05); it is interesting to stress that TEST became normal in HD. In addition, we observed a decrease of PRL after CC only in HD patients (p < 0.01). In summary, CC was able to partially correct most of the hormonal disturbances of the gonadal axis in uremic patients. PMID- 8459873 TI - Effects of renal failure on skeletal muscle. AB - In this cross-sectional study, we examined biopsies from the vastus lateralis muscle of 13 predialytic uremic men (mean age 46 +/- 8 years). Their average glomerular filtration rate was 14 +/- 7 ml/min x 1.73 m2 and their maximal exercise capacity, measured by standardized exercise test on a bicycle ergometer, was 184 +/- 45 W (94% of the expected norm). The proportion of type I fibers (type I%) in the uremic group was similar to that of the reference group (42 +/- 11 vs. 41 +/- 8% NS). The proportion of type IIA fibers (type IIA%) in the uremic group was higher than in the reference group (44 +/- 10 compared to 35 +/- 9%, p < 0.05). The proportion of type IIB fibers (type IIB%) was lower than in the reference group (13 +/- 8 vs. 21 +/- 8%, p < 0.05). Type I fiber area was similar to that of the reference group (4,768 +/- 1,033 vs. 4,627 +/- 1,112 microns 2, NS). Type IIA and type IIB fiber areas tended to be smaller than those of the reference group (type IIA fiber area: 4,515 +/- 929 vs. 5,213 +/- 1,288 microns 2, NS; type IIB fiber area: 3,953 +/- 1,066 vs. 4,406 +/- 1,582 microns 2, NS) with a type IIA area/type I area ratio which was significantly lower than in the reference group. Citrate synthase activity was 0.48 +/- 0.08 mu kat/g in the uremic group and 0.50 +/- 0.08 mu kat/g in the reference group, NS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8459874 TI - How frequent are hepatitis B virus markers in adult patients with glomerular diseases in a low endemic country? A French study from Paris and Saint-Brieuc. AB - In order to appreciate the frequency of hepatitis B virus (HBV) infection in patients with glomerular diseases in France, a low endemic country, we reviewed the series of patients biopsied in the years 1983-1989 in 2 departments of nephrology differing by the characteristics of the population. In Saint-Brieuc, where the population is almost exclusively Caucasian, with nearly no immigrant, HBsAg was not detected in any of the 86 patients. In Paris, a large number of patients come from highly or intermediately endemic regions. HBsAg was detected in 3 of 209 patients, 2 of the 75 patients with membranous nephropathy and 1 of the 32 patients with minimal-change nephrotic syndrome. These patients came from Africa and Asia. Therefore, in low endemic countries, the role of HBV infection in the etiology of glomerulonephritis is minimal. But, because of the late severity of the disease, screening remains essential in patients belonging to the high-risk groups. PMID- 8459875 TI - Serial changes of interleukin-6 and interleukin-8 levels in drain dialysate of uremic patients with continuous ambulatory peritoneal dialysis during peritonitis. AB - In this study, we investigated whether peritoneal dialysate interleukin-6 (IL-6) and IL-8 levels were elevated during peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients, with special reference to the high peritonitis occurrence (HPO) group. Serial measurements of IL-6 and IL-8 levels in dialysate before, during and after resolution of peritonitis were done in 13 CAPD patients with 15 episodes of peritonitis. Based on the peritonitis occurrence, 7 patients were assigned to the low peritonitis occurrence (LPO) and 6 patients to the HPO group. Marked elevation of IL-6 and IL-8 in drain dialysate occurred in the early period of peritonitis especially on the first 2 days in both groups. However, there were no significant differences between the groups in the levels of IL-6 and IL-8 in drain dialysate on the first day of peritonitis. However, the disappearance of peritoneal dialysate IL-8 level was faster in the LPO than in the HPO group. The decrease in IL-8 levels during peritonitis was faster than that of IL-6. Marked elevation of IL-6 and IL-8 in drain dialysate was found in the patient with peritonitis caused by Staphylococcus epidermidis and mixed gram-negative bacilli. Therefore, we hypothesize that when peritonitis occurs too frequently in a short period in the HPO group, more IL-6 and IL-8 have been produced in the peritoneum contributing to the ongoing peritoneal injury and/or fibrosis. PMID- 8459876 TI - Depressed phagocytosis in hemodialyzed patients: in vivo and in vitro mechanisms. AB - Infection is a frequent complication and the major cause of death among end-stage renal patients. Polymorphonuclear phagocytes (PMNL) are important in host defense mainly because of bacterial destruction by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-related free radical production following phagocytosis. In this study, hexose monophosphate pathway glycolytic activity, delivering energy to NADPH oxidase, is evaluated in vivo and in vitro, in healthy controls and in dialyzed renal failure patients. Our results show a marked parallel and correlated inhibition in the response to three stimuli for phagocytic activity (Staphylococcus aureus, formyl-methionine-leucine-phenylalanine, phorbol myristic acid) in predialysis samples. These data point to a main suppression of metabolic pathways, possibly beyond protein kinase C. This response is further suppressed at the 15th minute of cuprophane dialysis, for all stimuli studied (-40 to -94%; p < 0.001) except PMA. PMNL response remains intact during dialysis with non complement-activating dialyzers. In vitro experiments confirm decreased PMNL glycolytic activity after the suspension of cuprophane fragments in normal whole blood. We conclude that polymorphonuclear cell energy delivery to NADPH oxidase is impaired in patients with end-stage renal failure. The impaired response against various stimuli is different in predialysis blood samples compared to samples collected during cuprophane dialysis, and may be related to two different conditions. These events probably contribute to the acquired immune suppression of uremia and the high incidence of infection among dialysis patients. PMID- 8459877 TI - D-lactate metabolism in patients with chronic renal failure undergoing CAPD. AB - To clarify the D-lactate metabolism in patients with chronic renal failure undergoing CAPD, plasma levels, loaded doses and urinary excretion of D-lactate were measured. In addition, D-2-hydroxy acid dehydrogenase activities in resected and autopsied specimens were measured. The daily loaded dose of D-lactate by CAPD was 88.9 +/- 1.29 mmol and urinary excretion was negligible. There was no tendency for the plasma D-lactate to accumulate. The enzyme activity was detected in the liver, kidney and pancreas tissues both in the resected and autopsied specimens. The above findings indicate that the loaded D-lactate is catabolized in patients with chronic renal failure undergoing CAPD, and D-2-hydroxy acid dehydrogenase is responsible for the metabolism of D-lactate in humans. PMID- 8459878 TI - Effect of prostaglandins on renal function in uninephrectomized humans. AB - We examined the effects of unilateral nephrectomy (UN) and administration of indomethacin in 15 healthy humans. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), urine flow, sodium and potassium excretions, urinary excretion rate of prostaglandin E2 (PGE2) and 6-keto prostaglandin F1 alpha (6 keto PGF1 alpha) in the remaining kidney were all significantly (p < 0.01) increased 10 days after UN. Indomethacin administered at 75 mg/day for 3 days abolished the increase in GFR, ERPF and sodium excretion with reduced urinary excretion rate of PGE2 and 6-keto PGF1 alpha but not the increase in urine flow and potassium excretion. These findings suggest that renal prostaglandins may play a role in renal functional adaptation following UN. PMID- 8459879 TI - Acute renal failure following physical torture. AB - Ten cases of acute renal failure (ARF) were seen in the period from July 1990 to August 1991 in the Nephrology Department of the SIMS Hospital, Srinagar. All were males in the age group of 18-28 years and in apparent good health when apprehended by the police. There was alleged history of physical torture of different types. All had been beaten on the buttocks, back and limbs; in addition, 2 cases had been given repeated electric shocks and 1 case put to 'sit and-stand' exercise for about 3 h. The interval between the first day of torture till they came to our observation varied from 4 to 11 days. The main clinical features at the time of presentation were generalized aches and weakness (10), oligoanuria (9), vomiting (8), hypertension (6), acidosis (10), facial puffiness and pedal edema (6), fever and shivering (3), pulmonary edema (2), stupor (4), and hyperkalemia (5). All the cases had an established ARF (serum creatinine 668 1,997 mumol/l and serum urea 21.8-71.8 mmol/l) when first seen. Muscle enzymes, creatine phosphokinase, lactic dehydrogenase and serum glutamic oxaloacetic transaminase were all significantly raised indicating rhabdomyolysis. All showed evidence of myoglobin casts in urine. Nine had oliguric and 1 had nonoliguric ARF. All except the 1 case with nonoliguric ARF were managed with peritoneal dialysis and/or hemodialysis. All recovered. Early recognition of ARF is important since the main attention in such cases is directed towards the surgical aspect. PMID- 8459880 TI - Role of fibronectin in immune glomerulonephritis. AB - There is already a considerable amount of evidence suggesting that fibronectin (Fn) plays an important role in the pathogenic process in some forms of glomerulonephritis (GN). It has been postulated that Fn may participate in the progression or regression of glomerular diseases. The Fn is presented in the kidney as a normal component of the mesangium, and it is increased in the expanded mesangium in various forms of GN. This paper reports our efforts to investigate the role of Fn in plasma and kidney in patients with GN. Using monoclonal antibodies against human Fn in the ELISA and immunohistoperoxidase techniques to evaluate Fn, we investigated its quantity in connection with clinical state and morphological findings. We studied 93 patients with GN and 26 renal biopsies. The patients with active forms of mesangial proliferative, membranoproliferative and membranous GN showed increased plasma Fn, and the highest levels were in patients with nephrotic syndrome. Increased tissue Fn correlated with mesangial expansion and with IgG and C3 deposits. We speculate on possible mechanisms of the involvement of Fn in human chronic GN. PMID- 8459881 TI - L-gulono-gamma-lactone oxidase is the enzyme responsible for the production of methylguanidine in the rat liver. AB - A methylguanidine-synthesizing enzyme localized in rat liver microsomes produces methylguanidine via the intermediates creatone A and creatone B from the substrate, creatol, a substance produced from creatinine mainly by reaction with hydroxyl radicals. This enzyme has been identified as L-gulono-gamma-lactone oxidase (EC 1.1.3.8). However, no corresponding activity was found in extracts from human livers. PMID- 8459883 TI - Chylous ascites associated with acute pancreatitis in a patient undergoing continuous ambulatory peritoneal dialysis. AB - We report on a case of chylous ascites associated with acute pancreatitis secondary to gallbladder stone disease, in a patient undergoing continuous ambulatory peritoneal dialysis. The initial clinical presentation was one of bacterial peritonitis, with later appearance of chylous peritoneal drainage. Diagnosis was suggested by abdominal computed tomography and confirmed by surgical exploration. We discuss the main diagnostic keys of peritoneal dialysis associated pancreatitis and the possible etiologic role of this entity in chylous ascites of these patients. PMID- 8459882 TI - Purification of methylguanidine synthase from the rat kidney. AB - Methylguanidine (MG)-synthesizing enzyme was purified from rat kidney lysosomes and peroxisomes. The enzyme was a flavoprotein with a molecular weight of about 37,000 and oxidized creatol to produce MG. The present results suggest that the reaction mechanism of this enzyme is different from that of L-gulono-gamma lactone oxidase (EC 1.1.3.8) isolated from rat liver microsomes. PMID- 8459884 TI - Relapsing steroid-responsive idiopathic acute interstitial nephritis. AB - A 49-year-old woman developed acute renal failure secondary to interstitial nephritis. Her clinical history, complementary studies and two renal biopsies could not establish the etiology. She showed signs of incomplete Fanconi syndrome. Treatment with corticosteroids was very effective, though she tended to relapse. We comment briefly on some aspects of idiopathic acute interstitial nephritis. PMID- 8459885 TI - Iodine-induced sialadenitis: report of 4 cases and review of the literature. AB - Sialadenitis after administration of iodine compounds is rare. In this paper we report 4 hemodialysis patients who suffered from this rare manifestation of iodism and review the literature. PMID- 8459886 TI - 5-year treatment of the chronic syndrome of inappropriate secretion of ADH with oral urea. AB - We report the case of a patient with an idiopathic syndrome of inappropriate secretion of ADH for more than 6 years. Water restriction was effective only during hospital care but was socially difficult to maintain at home, so that the patient presented frequent symptoms of water intoxication. Normal natremia was also obtained with a high salt intake (9 g/day) but this induced leg edema mild dyspnea and gastric intolerance. The patient was however successfully treated for more than 5 years without any side effects with oral urea (30 g/day) allowing her a normal fluid intake (1-1.5 liters/day). Oral urea, even during long periods, is a safe and effective therapeutic approach for patients with chronic SIADH which is not controlled by water restriction alone. PMID- 8459887 TI - Azathioprine-induced pure red blood cell aplasia in a renal transplant recipient. PMID- 8459888 TI - Cyclophosphamide pulse therapy in frequently relapsing nephrotic syndrome. PMID- 8459889 TI - Use of subcutaneous thymopentin in the treatment of steroid-dependent relapsing minimal-change nephrotic syndrome. PMID- 8459890 TI - Simvastatin does not increase lipid peroxidation in uremic patients. PMID- 8459891 TI - Cystinuria and renal transplantation. PMID- 8459892 TI - A case with endocardial cushion defect and horseshoe kidney. PMID- 8459893 TI - Allergic cross-reactivity to teicoplanin and vancomycin. PMID- 8459894 TI - Cytokine levels in patients with Balkan nephropathy. PMID- 8459895 TI - Accumulation of low molecular weight proteins in patients treated with repeated hemodialysis. PMID- 8459896 TI - Significance of platelet-derived microparticles in uremia. PMID- 8459897 TI - [Evaluation of cerebral circulation by SPECT]. PMID- 8459898 TI - [Pathogenesis and management of secondary neural damage in head trauma patients: analysis of patients who talk and deteriorate "fulminantly"]. AB - To clarify the pathogenesis and management of secondary neural damage after head trauma, we characterized the clinical features and CT findings in nine patients who talked and deteriorated "fulminantly". The patient who talks and deteriorates "fulminantly" is defined as a patient who talks (verbal score of Glasgow Coma Scale > or = 4) on admission, and subsequently shows a rapid neurological deterioration to develop an anisocoria and/or a decerebrated posture within 24 hours after trauma. Nine (8%) out of 118 patients with severe head trauma satisfied the definition mentioned above. The mechanism of injury was a fall in 5 patients and a road traffic accident in 4. Plain skull X-ray manifested a linear skull fracture in 8 out of 9 (89%). Although they were almost alert and talked on admission, all of these 9 patients developed an anisocoria within 6 hours after trauma. Prior to the rapid neurological deterioration, in spite of their good consciousness, they characteristically showed a variety of CT abnormalities including subdural hematoma (SDH), intracerebral hematoma (ICH) and subarachnoid hemorrhage. Following the rapid neurological deterioration, 7 out of 9 patients underwent surgical treatment for hematoma evacuation using a large decompressive craniectomy. Clinical outcomes were 2 good recoveries, 1 moderate disability, and 6 deaths. Causes of the rapid neurological deterioration determined by CT and surgery were: 1) an enlarged SDH in 6 patients, 2) an enlarged ICH in 4 patients, and 3) a worsened brain swelling associated with SDH in 3 cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8459899 TI - [Syringomyelia secondary to adhesive arachnoiditis: clinical profiles and efficacy of shunt operations]. AB - The authors report nine cases of syringomyelia secondary to adhesive arachnoiditis treated in our institute from 1982 to 1991. Neurological signs, radiological features, and results of surgical treatment were reviewed. Common initial manifestations in association with syringomyelia were spastic paraparesis in 8 patients (88.9%), regional sensory loss in 4 (44.4%), neurogenic bladder in 4 (44.4%), and somatic pain in 2 (22.2%). All the neurological symptoms or signs progressed gradually for years. All the patients were treated with various modes of shunt operations, including syringo-peritoneal shunt in seven patients, syringo-subarachnoid shunt in one, and ventriculo-peritoneal shunt in one, respectively. Three patients who failed to resolve their major complaints after the first surgery further received syringo-peritoneal shunts. Postsurgical follow up periods ranged from 18 months to 10 years. Serial MR imaging revealed a significant reduction of the size of syringomyelia in 8 of 9 patients. However only 6 patients showed certain improvement of neurological deficits. Three patients who failed to improve clearly had a long (beyond 15 years) history of syringomyelia before the first surgical treatment. A total of 11 syringo peritoneal shunts were done in 8 patients of whom 5 patients improved neurologically. It was noticed that 4 of 5 successful syringo-peritoneal shunts were placed in the caudal level of the syrinx. In conclusion, syringo-peritoneal shunt may be at present an optimal mode of surgical management for syringomyelia secondary to adhesive arachnoiditis. In addition, we would like to recommend that follow-up serial MR imaging be done for patients having adhesive arachnoiditis in order to detect syringomyelia as early as possible. PMID- 8459900 TI - [Three months angiographic follow-up after successful percutaneous transluminal angioplasty]. AB - Percutaneous Transluminal Angioplasty (PTA) is applied to supra-aortic arteries. Although first follow-up angiography after coronary angioplasty is usually undergone three or four months later, there are few reports of follow-up angiography after PTA of supraaortic arteries. Because of this, we performed follow-up angiography three months after successful PTA on eight cases of stenosis in seven patients. Although no symptom due to restenosis occurred, it was shown to have occurred in one of four cases of internal carotid arterial stenosis. It was a case of ostial stenosis of a left common carotid artery. Restenosis occurred in neither two cases of subclavian arterial stenosis, nor in a case of left middle cerebral arterial stenosis. The overall restenosis rate was 25%. We suspect that it is important to perform a follow-up angiography after angioplasty of supra-aortic arteries, and our result suggests that the restenosis might occur before three months after PTA as well as after coronary angioplasty. PMID- 8459901 TI - [CT guided transsphenoidal surgery: report of nine cases]. AB - We have developed a Computed Tomography system for use in the operating room and applied this CT system to intraoperative monitoring during transsphenoidal surgery. This system includes Toshiba TCT-300 CT system, mobile CT scanner gantry, digitally controlled operating table and head fixation system. Between June 1989 and Dec. 1989, CT guided transsphenoidal surgery was carried out in 9 cases in our department. The suprasellar masses were visualized directly during transphenoidal surgery and were removed safely and efficiently. Under this CT monitoring system the surgeon can obtain accurate information about the location and volume of residual tumor as well as about the important surrounding deeper structure. Another advantage of this system is that the digitally controlled operating table makes it possible to keep the patient in a head-up position, which lessens oozing from the parasellar region during transsphenoidal surgery. We believe the best application of this method is that for pituitary tumor with moderate suprasellar extension. Nine cases were reported in this paper which were operated on using this system. To our knowledge, this is the first report of use of intraoperative CT monitoring during transsphenoidal surgery. PMID- 8459902 TI - [Monostotic fibrous dysplasia of the occipital bone]. AB - A case of monostotic fibrous dysplasia of the occipital bone in a 18-year-old female is described. She was admitted to our hospital with a hard, painless mass (5 x 5 cm) in the occipital region. Neurological examination and laboratory data revealed no abnormalities. Skull x-rays showed a radiolucent lesion with a sclerotic margin in the occipital bone. CT scan revealed an intradiploic multilocular mass separated by bone trabeculae. RI bone scan showed an abnormal uptake in this lesion. T1 and T2 MR image showed an abnormal low-intensity lesion in the occipital region. Operation was performed to verify the nature of the lesion, which was histologically confirmed to be an inactive fibrous dysplasia. Postoperative course was uneventful. Although its occurrence in the occipital bone is uncommon, fibrous dysplasia should be considered in the differential diagnosis of skull tumors. PMID- 8459903 TI - [Appearance of hallucinations and one-and-a-half syndrome after resection of a cavernous angioma located in the fourth ventricle floor]. AB - A patient is described who simultaneously suffered from hallucinations and one and-a-half syndrome following surgical resection of a cavernous angioma located on the fourth ventricle floor. A 30-year-old male was admitted having a 10 year history of progressive weakness and hypesthesia of the right extremities. Neurological examination revealed right hemiparesis and hemihypesthesia. A computerized tomography (CT) scan showed a well circumscribed mixed-density area at the left portion of the pontine tegmentum. Magnetic resonance imaging (MRI) indicated a mixed intensity core surrounded by hypointense regions on T2-weighted images. A red mulberry-like tumor was found, during surgical procedures, on the mid-and left-portion of the fourth ventricle floor. The tumor was totally resected and the histological diagnosis was cavernous angioma. Visual hallucinations occurred several times following surgery, being subsequently described as images of moving worms, a dump truck next to the bed, and a bed falling from the ceiling. The patient soon understood these objects were not real. He simultaneously exhibited left lateral gaze palsy associated with left internuclear ophthalmoplegia i.e., one-and-a-half syndrome. Three months after surgery the visual hallucinations disappeared but the one-and-a-half syndrome was incompletely resolved. According to the neurological signs and the MRI results, the lesion site was considered to extend from the left lower pons to the midbrain. Previously reported operations of cavernous angioma of the fourth ventricle floor are also described. PMID- 8459904 TI - [Surgical excision of a cavernous angioma of the cerebral peduncle by orbito fronto-malar approach]. AB - A case with cavernous angioma at the left cerebral peduncle was cured surgically. A 36-year-old male was admitted with complaints of right facial palsy, right motor disturbance and cheiro-oral syndrome. CT revealed a round high-density mass in the left cerebral peduncle and thalamus. Angiography showed no abnormality. MRI showed a round high-intensity mass on T1-and T2-weighted image in the left thalamus, which meant hematoma at a subacute stage and mixed-intensity core in the left cerebral peduncle, which was cavernous angioma. Symptoms disappeared, and high-density also disappeared gradually, but rebleeding occurred. Because of this, an operation was performed by the orbitofrontmalar approach. Hematoma and angioma were removed under ABR and SEP monitor, which showed no abnormality during the operation. Histological examination of the surgical specimen revealed that the abnormal vessels were cavernous angioma. The postoperative course was uneventful without cosmetic problems. PMID- 8459905 TI - [Creutzfeldt-Jakob disease transmitted by cadaveric dural graft: a case report]. AB - We report a case of Creutzfeldt-Jakob disease in a 38-year-old man, transmitted by a cadaveric dural graft. In August 1985, he underwent cranial nerve decompression for hemifacial spasm and received a cadaveric dural graft for dural closure. He had been well until he began to complain of blurred vision and headache in May, 1990. He developed dementia, myoclonus and urinary incontinence over the subsequent 3 months. He was admitted to our hospital in August, 1990. On admission, he was somnolent and showed gait disturbance, myoclonus in extremities and elevated deep tendon reflexes symmetrically. The results of analysis of blood, urinary and cerebrospinal fluid were normal. The initial computed tomography (CT) and magnetic resonance imaging detected no abnormality. Electroencephalography showed typical periodic synchronous discharge (PSD). There was progressive worsening of his neurological symptoms, and this developed into mutism in September, 1990. CT, 11 months after clinical onset, showed marked enlargement of the ventricles and the sulci. In view of his rapid worsening clinical course, PSD findings on electroencephalography, and delayed progressive changes of CT findings, the diagnosis of CJD disease was made. The cadaveric dural graft was suspected as the cause of the patient's condition. Since Thadani et al reported the first case of CJD transmitted by cadaveric dural graft in 1988, 3 other cases have been reported. This is most likely the 5th reported case of Creutzfeldt-Jakob disease transmitted by cadaveric dural graft. PMID- 8459906 TI - [A rare case of infraclinoid aneurysm accompanied with pituitary adenoma extending over the extrasellar space]. AB - A 39 year-old female patient suffering from amenorrhea over the course of the last 14 years was admitted to our hospital on Dec. 12, '89. Computed Tomography revealed a relatively high-density mass extending over the suprasellar portion and the sphenoid sinus. Enlargement and destruction of the sella turcica was demonstrated clearly by the plain craniogram ++. Right carotid angiography demonstrated an open siphon and a medially pointing aneurysm on the right anterior siphon. Two staged operations were performed. On Jan. 23, '90, a transsphenoidal operation was performed to remove the part of the tumor invading the sphenoid sinus. Two weeks later, on Feb. 9, '90, a transcranial operation was carried out for extirpation of the residual adenoma and direct neck clipping of the aneurysm. The tumor was subtotally removed through a left fronto-lateral craniotomy. By drilling away the tuberculum sellae and the planum sphenoidal the aneurysm was completely clipped via a contralateral approach. The postoperative neuroradiological examinations demonstrated that the aneurysm was clipped successfully and the adenoma was extirpated almost totally. PMID- 8459908 TI - Current bibliographies of neuropeptides prepared by the University of Sheffield Biomedical Information Service. PMID- 8459907 TI - [Isolated trochlear nerve palsy caused by mixed dural-pial arteriovenous malformation of the anterior cranial fossa: a case report]. AB - A 62-year-old male was admitted to our hospital in May, 1985, with double vision, which had persisted for 1 month. The neurological examination revealed left trochlear nerve palsy. A cerebral angiogram showed an arteriovenous malformation at the anterior cranial fossa. The malformation was mainly fed by the left anterior ethmoidal artery which branched off from the orbital branch of the left middle meningeal artery. There was a marked enlargement of anastomosis between the orbital branch of the middle meningeal artery and the recurrent meningeal branch of the lacrimal artery. Bilateral distal branches of the internal maxillary arteries, bilateral anterior falx arteries and the left fronto-orbital artery were also involved in supplying the AVM. The dilated fronto-orbital vein was the main drainer which emptied into the pterygoid plexus via the uncal vein and the sphenoparietal vein. In June 1985, the nidus involving the dura at the region of the cribriform plate and olfactory bulb was totally removed through a left frontal craniotomy. Postoperatively, the isolated left trochlear nerve palsy improved completely within a few days. This is the first reported case of isolated trochlear nerve palsy caused by a mixed dural-pial arteriovenous malformation of the anterior cranial fossa. We concluded that the etiology of isolated trochlear nerve palsy consisted of nerve compression due to the dilated orbital branch of the middle meningeal artery within the superior orbital fissure. PMID- 8459909 TI - Arginine-vasopressin release mediates the aldosterone secretagogue effect of neurotensin in rats. AB - Acute and chronic systemic administrations of neurotensin (NT) and arginine vasopressin (AVP) significantly increases plasma aldosterone concentration (PAC) in rats. Deamino-Pen1, Val4, D-Arg8-vasopressin (AVP-A), a potent AVP antagonist, completely reversed both acute and chronic aldosterone secretagogue actions of NT and AVP. AVP-A acute administration did not affect basal PAC, while chronic AVP-A treatment significantly lowered it. Taken together our findings suggest that both NT and AVP exert a marked aldosterone secretagogue effect in rats, and that the mechanism underlying NT action may involve the stimulation of AVP release. Moreover, they indicate that endogenous AVP plays an essential role in the maintenance of the mineralocorticoid secretory capacity of rat zona glomerulosa. PMID- 8459910 TI - Neural and non-neural origin of calcitonin gene-related peptide (CGRP) in the gastric mucosa. AB - We have used immunohistochemistry and in situ hybridization histochemistry to visualize CGRP and the mRNA encoding the CGRP precursor in the stomach. CGRP is present in nerve fibers in the mucosa. CGRP mRNA and CGRP itself are also found in non-neural cells in the lamina propria. These cells are likely to be macrophages or B-lymphocytes. PMID- 8459911 TI - Identification, localization and developmental studies of rat prepro thyrotropin releasing hormone mRNA in the testis. AB - Thyrotropin-releasing hormone (TRH) plays the central regulatory role in the hypothalamic-pituitary-thyroid axis, but is also present in many extra hypothalamic loci. The adult rat testis has been identified previously as a source of hypothalamic neuropeptides including TRH. To investigate whether the TRH gene is transcribed in testis, the identification and localization of prepro(pp) TRH mRNA and TRH were studied. Northern blot analyses of ppTRH mRNA in the adult rat testis showed a 2.0 kb band, hybridized with a ppTRH cRNA probe. This band was 0.4 kb greater than the 1.6 kb hypothalamic band. The concentration of ppTRH mRNA in the adult testis was approximately 13% of that found in the hypothalamus. Developmental studies of testicular ppTRH mRNA revealed that no ppTRH mRNA could be detected at the earliest stage (day 8). However, hybridization signals were detected on day 20 and increased progressively on days 35, 45 and 70 by 5.8, 6.4, and 9.8-fold, respectively. In addition, ppTRH mRNA was determined in Leydig cells by Northern analyses of elutriated testicular cell fractions. TRH was also measured in the rat testes at different developmental stages by RIA. TRH concentrations paralleled ppTRH mRNA during development. TRH was localized to Leydig cells by immunohistochemistry. These results indicate that ppTRH mRNA and TRH are present in the rat testis, especially in the Leydig cells. The changes of ppTRH gene expression and the concentration of TRH in the rat testis are developmentally dependent. TRH may function as a new paracrine or autocrine regulator of testicular function. PMID- 8459912 TI - Identification of multiple tachykinins in bovine adrenal medulla using an improved chromatographic procedure. AB - Comparison of data based on the reverse-phase HPLC with two ion-pairing reagents, trifluoroacetic acid (TFA) and heptafluorobutyric acid (HFBA), together with the use of two antibodies, has allowed us to identify the various tachykinins in the bovine adrenal medulla. The results show that substance P-like, neurokinin B like, and neurokinin A-like (including its extended forms, neuropeptide K and neuropeptide gamma) immunoreactivity are present in the bovine adrenal medulla. The concentration of SP-like immunoreactivity in the adrenal medulla was found to be substantially higher than that of NKA-like and NKB-like immunoreactivity. The strategy described here, using radioimmunoassay combined with HPLC employing TFA and HFBA as the ion-pairing reagents, should be useful for the identification of tachykinins and other peptides in the central and peripheral nervous system. PMID- 8459913 TI - A double-blind, comparative study of gadodiamide injection and gadopentetate dimeglumine in MRI of the central nervous system. AB - Seventy-nine patients with known or suspected central nervous system lesions were studied with MRI in a phase III double-blind study. Forty were given gadopentetate dimeglumine (Gd-DTPA) and 39 gadodiamide injection (Gd-DTPA BMA), a new low-osmolar nonionic contrast enhancing medium. The dosage was 0.1 mmol/kg body weight, corresponding to 0.2 ml/kg. Spin-echo sequences were performed before and immediately after injection. The safety and efficacy of the two contrast media were assessed. No changes were observed in blood pressure, heart rate or neurological status. Five adverse effects (two episodes of headaches, two of nausea and one of dizziness) were reported by 2 patients who received gadodiamide injection and 1 who received gadopentetate dimeglumine. All events were mild and their relationship to the contrast media was uncertain. For both contrast media statistically significant changes in serum iron were observed 24 h after injection. More than 70% of the patients had abnormal findings on MRI, and in 56% of these contrast enhancement of the abnormal structure or lesion was seen. Contrast enhancement provided the diagnosis in about 50%, changed it in 40% and increased diagnostic confidence in 95%. PMID- 8459914 TI - Magnetic resonance imaging of ganglion cell tumours. AB - The MRI and CT studies of four patients with ganglion cell tumours, one with a cerebellar gangliocytoma (Lhermitte-Duclos disease), and three with gangliogliomas are reported. MRI in Lhermitte-Duclos disease clearly demonstrated a mass of low signal intensity in the left cerebellum on T1-weighted spin-echo (SE) images and an area of high signal intensity with a blurred margin on T2 weighted SE images. These MRI studies were useful for delineating the lesion, which was verified at surgery. In the ganglioglioma, MRI demonstrated two isointense solid masses on T1-weighted SE images, which enhanced clearly with Gd DTPA. The enhancement study was advantageous in planning surgery. PMID- 8459915 TI - MRI of intracranial subependymoma: report of a case. AB - Subependymoma is a rare, benign intraventricular tumour and a case of septum pellucidum origin examined with CT and MR is reported. Well demarcated non enhancing mass with multiple small intratumoral cysts is demonstrated on CT and MR images. The differential diagnosis from ependymoma has some therapeutic implications but may not be possible by CT or MRI. PMID- 8459916 TI - Magnetic resonance imaging of xanthomatous meningioma. AB - A case of meningioma with extensive xanthomatous metaplasia occurring in the left frontal convexity of a 37-year-old woman is reported. The tumour was demonstrated as a hypodense mass with minimal enhancement on CT. Our findings suggest that magnetic resonance imaging may provide a clue to the diagnosis of meningiomas with extensive xanthomatous metaplasia when CT is less specific. PMID- 8459917 TI - Large vessel disease in Chinese patients with capsular infarcts and prior ipsilateral transient ischaemia. AB - Carotid angiography was carried out in 21 Chinese patients with acute capsular infarcts; all had had a previous ipsilateral transient ischaemic attack (TIA) or reversible ischaemic neurological deficit (RIND) during the preceding 6 months. Sixteen (group 1) showed lacunar capsular infarcts, and 5 (group 2) either "giant lacunae" or "striatocapsular infarcts". Angiography showed that 81% of group 1 and all group 2 patients had ipsilateral severe stenosis or occlusion of either the M1 segment of the middle cerebral artery or the internal carotid artery. Ten group 1 patients and 3 group 2 patients also had contralateral intra- or extracranial carotid artery stenosis. Apart from hypertension, other risk factors such as hyperfibrinogenaemia, polycythaemia, and low HDL-cholesterol level seem to play a role. Haemorheological abnormalities in the presence of atherostenosis at the orifice of lenticulostriate arteries and/or artery-to-artery embolism might be the cause of infarcts in the majority of the patients. A fifth of patients had recurrent large ipsilateral infarcts. Thus capsular lacunar syndromes with prior ipsilateral TIA or RIND are not as benign as previously thought, and they should indicate more intensive studies including cerebral angiography, and more vigorous therapy. PMID- 8459918 TI - Pure motor hemiparesis in a case of vertebrobasilar arterial ectasia. AB - A case of pure motor hemiparesis due to a pontine lacunar infarct is reported. Infarction was related to vertebrobasilar ectasia identified on CT, MRI and MR angiography. MR studies provide accurate information on anatomical location, residual lumen, partial thrombosis, mass effect on brain stem and CSF pathways and vascular complications. PMID- 8459919 TI - Cerebral fat embolism studied with MRI and SPECT. AB - In a patient with fat embolism to the brain CT showed no abnormality. MRI performed after recovery from coma, when the patient had aphasia and quadriparesis, demonstrated multiple high signal abnormalities in the white matter on both T1- and T2-weighted images. HMPAO-SPECT showed left-sided hypoperfusion which resolved in parallel with clinical improvement 1 month later. PMID- 8459920 TI - Thrombosis of the right vein of Labbe: radiological and clinical findings. AB - A rare case of aseptic thrombosis of the right vein of Labbe in a young woman is reported. Cerebral venous thrombosis was suggested by computed tomography and confirmed by angiography. Mild left-sided neurological deficits resolved almost completely. The combination of a nonspecific clinical picture with an atypical lesion on CT may favour the diagnosis of cortical venous thrombosis. PMID- 8459921 TI - Contribution of meningeal arteries to cerebral arteriovenous malformations. AB - We studied 52 patients with cerebral arteriovenous malformations (AVMs) by selective angiography and found that half received supply from meningeal branches of the external carotid artery. The frequency of meningeal arterial contribution was significantly higher in superficial AVMs, especially in the temporal, parietal and occipital regions. Larger lesions and higher shunt with steal phenomena on angiography were other factors favouring a meningeal arterial contribution. Diffuse AVMs with pial arterial networks around the nidus commonly received meningeal blood supply. In the past, meningeal feeders have been thought to be congenital, but this study suggests that they may develop during growth of the AVM. PMID- 8459922 TI - Posterior cranial fossa dural arteriovenous malformation with a varix mimicking a thrombosed aneurysm: case report. AB - Dural arteriovenous malformations (AVMs) in the posterior cranial fossa are relatively infrequent. Intradural haemorrhage is one of their specific complications. Angiographic demonstration of varices or aneurysmal structures is one of the hallmarks of severe cases. We report a patient with posterior cranial fossa dural AVM associated with a varix mimicking a thrombosed aneurysm on CT and MRI. Internal carotid and vertebral angiography failed to demonstrate an aneurysm, but external carotid injection revealed a dural AVM affecting the sigmoid sinus, and a varix. The AVM was completely eliminated by embolization. When a dural AVM is suspected clinically selective angiography should be performed to confirm the diagnosis even when CT or MRI do not show dilated vessels. PMID- 8459923 TI - Anomalous origin of the parieto-occipital artery: case note. PMID- 8459924 TI - Disseminated tuberculomas in spinal cord and brain demonstrated by MRI with gadolinium-DTPA. AB - Intramedullary tuberculoma is rare, and there has been no report of concurrent intramedullary and intracerebral tuberculomas. We report a 30-year-old man with miliary tuberculosis of the lung. He suffered sudden paraplegia due to tuberculomas in the thoracic spinal cord and MRI showed more tuberculomas in the cervical spinal cord, brain stem, and cerebral and cerebellar hemispheres. The tuberculomas were isointense on the T1-weighted images, and hyperintense on the T2-weighted images; there was marked enhancement with intravenous gadolinium DTPA. All the tuberculomas were very small 1 year after antituberculous chemotherapy. PMID- 8459925 TI - Invasive aspergilloma of the skull base. AB - Aspergillus infection originating in the nasal cavity or paranasal sinuses is a rare cause of benign, locally invasive disease affecting the skull base. We describe a case in which extensive disease led to bilateral proptosis and invasion of the anterior cranial fossa. PMID- 8459926 TI - Diffuse pneumocephalus due to Clostridium septicum cerebritis in haemolytic uraemic syndrome: CT demonstration. AB - The computed tomography finding of diffuse pneumocephalus due to infection by gas forming organisms is very unusual. We report such a case due to secondary infection by Clostridium septicum in a child with diarrhoea-associated haemolytic uraemic syndrome. PMID- 8459927 TI - MRI in acute transverse myelopathy. AB - The MRI examinations of seven patients with acute transverse myelopathy (ATM) were analysed. The patients were examined 2-5 times during the course of their disease with short and long TR/TE spin-echo sequences in the sagittal projection. A previous history of autoimmune disorder and/or signs of infection at the onset of ATM were present in all cases. Cerebrospinal fluid analysis showed local synthesis of immunoglobulin in the nervous system in three cases and signs of infectious myelitis in one. During the acute phase four patients had local enlargement of the cord and all had increased signal on long TR/TE sequences. The outcome was grave in the majority of patients and there seemed to be a correlation between the degree of cord enlargement, persistence of increased signal intensity and limited recovery. Atrophy and remaining high signal intensity were noted on late MRI in patients with poor outcome. In one patient with probable anterior spinal artery occlusion, cavitation of the cord was seen. PMID- 8459928 TI - Appearances of posterior osteophytes after sound anterior interbody fusion in the cervical spine: a high-definition computed myelographic study. AB - Whether posterior osteophytes in the cervical spine resorb after anterior interbody fusion is controversial. Previous studies have only used plain films. In order to study remodelling, a retrospective study of 53 patients using high definition CT was performed. There was no evidence of remodelling or resorption of osteophytes and persistent osteophytes continued to deform the spinal cord for up to 12 years after fusion. The importance of this in relation to cervical spinal surgery is that every effort should be made to remove posterior osteophytes during anterior interbody fusion. PMID- 8459929 TI - Recognition of abnormalities on computed scout images in CT examinations of the head and spine. AB - We investigated the information which can be obtained from the computer-generated digital radiographs ("scout images") performed for CT examinations. One hundred CT examinations of the head and one hundred of the spine were randomly selected and retrospectively reviewed: the head scout images were acquired in the lateral projection, and those of the spine in the lateral and/or anteroposterior projections. In 122 patients with demonstrable pathology on the CT sections or the scout image, a total of 154 abnormalities was found, of which 31 (20%) were identified only on the scout images. Eight (25.8% of this number) required additional clinico-radiologic study and were therefore designated as clinically pertinent positives. This study demonstrates that the CT scout image may contain considerable, clinically relevant information which is not available on, or is complementary to, the CT sections. PMID- 8459930 TI - MRI of paraganglioma of the cauda equina. PMID- 8459931 TI - MRI in craniofacial fibrous dysplasia. AB - Five patients with biopsy-proven craniofacial fibrous dysplasia underwent MRI with T1- and T2-weighted sequences and a gadolinium-enhanced T1-weighted spin echo sequence. Low to intermediate signal intensity was usually seen in the largest part of the lesion on both spin-echo sequences, but smaller regions of hyperintensity on T1- and T2-weighted images and intermediate signal intensity throughout a lesion on T1-weighted images were also seen. All lesions enhanced but only two became iso- or hyperintense compared to fat. High clinical and pathological activity in three cases correlated with high signal intensity on both spin-echo sequences and with strong enhancement in two of the three. The presence of large veins or sinusoids on pathological examination did not correlate with the enhancement pattern. PMID- 8459932 TI - Three-dimensional CT of the middle ear and adjacent structures. AB - Three-dimensional (3D) computed tomography of the middle ear and adjacent structures has been carried out in two cadaveric heads from axial and coronal high-resolution images. The structures shown on the images of the walls of the tympanic cavity are illustrated. The usefulness and limitations of the technique, in this region, are discussed: use of grey level volumes at the surface of the slices and the inclusion of structural landmarks is emphasized. The 3D representations show the anatomical spacial relationships of the small structures in and around the middle ear to advantage. The information may be of use in surgical orientation. PMID- 8459933 TI - Metastatic hypernephroma to the larynx: an unusual presentation. AB - We report a renal cell carcinoma which presented as a metastasis to the larynx. The only preoperative clue to the diagnosis was its hypervascularity. PMID- 8459934 TI - Care of the HIV-infected woman should have a holistic focus. PMID- 8459935 TI - Reader has questions about Medical Assistance policies. PMID- 8459936 TI - NPs must take advantage of available opportunities. PMID- 8459937 TI - Abortion issue is more complex than many realize. PMID- 8459938 TI - Ohio practice barriers frustrate experienced NP. PMID- 8459939 TI - The diagnostic puzzle and management challenge of Raynaud's syndrome. AB - Raynaud's syndrome manifests as a progressive color change of the fingers in response to cold, vibration or stress; the digits first turn white, then blue and finally red. The condition is called Raynaud's disease when it is a benign, primary condition. When it is secondary to another disease, such as lupus, scleroderma or atherosclerosis, it is termed Raynaud's phenomenon. Laboratory tests, i.e., complete blood count, chemistry screen, antinuclear antibody, lupus erythematous test and rheumatoid factor, should be used to seek underlying diseases before the symptoms are manifest. Other tests should be selected as indicated by the history and physical. There are many adjustments in lifestyle and working conditions that the patient can use to minimize the symptoms of Raynaud's syndrome. The primary care provider has an important role in teaching patients to protect their hands from the effects of cold, stress, nicotine and vibration. Adaptive devices and protective clothing minimize the symptoms of Raynaud's syndrome. PMID- 8459940 TI - Cerumen-impaction management for clients of all ages. AB - A cerumen plug in the external auditory canal can cause dizziness, pain, itching, ringing or decreased hearing. These symptoms are particularly distressing to elderly clients who may already have compromised hearing or be experiencing changes in functional ability. A cerumen plug that causes hearing impairments can retard children's educational and psychosocial development. This article focuses on the physiology of cerumen, the risk factors of cerumen plugs and the best way to remove cerumen in clients of all ages. The contraindications and complications of aural lavaging and instrument removal of cerumen are discussed. An ear irrigation flow sheet is also included for ambulatory clinical use. PMID- 8459941 TI - Fertility awareness as a component of sexuality education. Preliminary research findings with adolescents. AB - Fertility awareness refers to the observation and interpretation of cervical mucus, often called vaginal discharge. A woman's cervical-mucus pattern indicates the time of ovulation and differentiates the fertile and infertile phases of the menstrual cycle from each other. Fertility awareness enables a woman to know when pregnancy can and cannot occur on a daily basis during each menstrual cycle. There has been, to date, almost no exploration of the appropriateness of fertility-awareness instruction for adolescents. A review of the literature on adolescent cognitive development, sexual activity, knowledge of fertility and contraceptive risk-taking behavior is presented. Based on the literature review, a theoretical rationale for fertility-awareness instruction as a unique sex education curriculum for adolescents is proposed. The content and teaching techniques of a fertility-awareness presentation for teenagers is described. Directions for future research in fertility-awareness instruction for teenagers, and the need for long-term follow-up to assess the effects of such education on teenagers' sexual activity and contraceptive use are discussed. PMID- 8459942 TI - A second opinion. PMID- 8459943 TI - Author urges closer look. PMID- 8459944 TI - Hold on to X-rays. PMID- 8459945 TI - OPD visits are not random events. PMID- 8459946 TI - Oral medicine: a history and a point of view. PMID- 8459947 TI - Oral medicine: it's basic dentistry. PMID- 8459948 TI - A clinician's view of the HIV question. PMID- 8459949 TI - What you don't see can hurt you. AB - Although AVMs are quite rare, at least two generalizations can be drawn from this case. First, don't rush into treatment. Time spent in the initial diagnosis and treatment planning is time well spent. Carefully evaluate the signs and symptoms, develop a good initial differential diagnosis, and if the facts just don't fit, expand your differential diagnosis. Second, take advantage of continuing education courses in oral diagnosis, oral pathology and oral medicine. This is certainly the best way to keep current, increase your diagnostic knowledge and expand your differential diagnoses. Finally, I hope this case presentation makes clear that what you don't suspect, you seldom see, and what you don't see can hurt you and your patients. PMID- 8459950 TI - Oral medicine: a bedrock of dental practice. PMID- 8459951 TI - Maintaining social responsibility in the mission of dentistry. PMID- 8459952 TI - Intrauterine pressure wave characteristics of the upper and lower uterine segments in parturients with active-phase arrest. AB - OBJECTIVE: To determine the gradient of pressure between the upper and the lower uterine segments of parturients with non-progressing labor and to see whether the gradient correlates with subsequent successful oxytocin augmentation. METHODS: Fifteen women with active-phase arrest of labor were monitored with two intrauterine pressure transducers before and after oxytocin augmentation. Seven parturients without arrest of labor were evaluated for comparison. One intrauterine pressure transducer was inserted into the upper and one into the lower uterine segment of each subject. Overall, 444 contractions were assessed using the mean active pressure method. RESULTS: A total of 16 patients delivered vaginally. Nine received oxytocin augmentation, and all had significantly higher pressure in the upper segment than in the lower both before and after oxytocin (P < .001). Six women delivered by cesarean had a reversed gradient of uterine activity, with the lower segment contracting significantly more strongly than the upper uterine segment both before (P = .002) and after oxytocin (P = .001). CONCLUSION: Pressure gradients between the upper and lower uterine segments in the active phase might predict the likelihood of success of oxytocin augmentation. PMID- 8459953 TI - Maternal and neonatal outcomes after prolonged latent phase. AB - OBJECTIVE: To examine the association of prolonged latent phase with cesarean risk, subsequent labor abnormalities, and other adverse maternal and neonatal outcomes. METHODS: Patients with prolonged latent phase were compared to patients with normal latent phase. We studied 10,979 singleton vertex deliveries of at least 37 weeks' gestation. Patients with risk factors for adverse outcome known before labor were excluded from the analysis. RESULTS: Seven hundred thirteen patients (6.5%) had prolonged latent phase. Subsequent labor abnormalities were more frequent among patients with prolonged latent phase (42.9 versus 16.3%; P < .05), as was cesarean delivery (24.4 versus 6.9%; P < .05). Need for neonatal resuscitation, thick meconium, maternal fever, low 5-minute Apgar score, intensive care nursery admission, lengthened maternal and newborn hospital stays, and higher estimated blood loss were all significantly more frequent in patients with prolonged latent phase after controlling for mode of delivery. Multivariate linear logistic regression models were created to determine whether these risks actually reflected the prolonged latent phase. The first model controlled for other labor abnormalities, parity, epidural use, and macrosomia and showed prolonged latent phase to be associated with an increased risk for cesarean delivery (relative risk [RR] 1.65, 95% confidence interval [CI] 1.32-2.06). The second model controlled for other labor abnormalities, postdates, thick meconium, mode of delivery, and prolonged rupture of membranes and showed that both the need for newborn resuscitation and 5-minute Apgar scores less than 7 were significantly more frequent in association with a prolonged latent phase (RR 1.37 and 1.97, 95% CI 1.15-1.64 and 1.23-3.16, respectively). CONCLUSIONS: Prolonged latent phase is independently associated with an increased incidence of subsequent labor abnormalities, need for cesarean delivery, depressed Apgar scores, and need for newborn resuscitation. The presence of prolonged latent phase should alert the clinician to an increased risk for further problems during the labor. PMID- 8459954 TI - Elective induction versus spontaneous labor after sonographic diagnosis of fetal macrosomia. AB - OBJECTIVE: To test the hypothesis that elective induction of labor, compared to spontaneous labor, reduces the cesarean rate in women with a sonographic diagnosis of fetal macrosomia. METHODS: Sonography results over a period of 27 months were used to select 262 consecutive patients who met the following inclusion criteria: singleton pregnancy at term, estimated fetal weight (EFW) at the 90th percentile or greater, and delivery at our institution. The subjects were divided into four groups based on obstetric management: spontaneous labor (N = 115), elective induction of labor with macrosomia as the sole indication (N = 44), induction of labor for other maternal or fetal indications (N = 48), and elective cesarean delivery (N = 55). The analysis focused on the first two groups. These were compared regarding cesarean rate, indications for cesarean, and shoulder dystocia rate. Multiple logistic regression was used to control for potential confounders. RESULTS: With elective induction, the cesarean rate was 57%, significantly higher than the 31% rate with spontaneous labor (P < .01). The induced group also had a significantly higher EFW and birth weight. When logistic regression was used to control for birth weight, parity, and care provider, elective induction was still associated with a higher risk of cesarean delivery than was spontaneous labor (adjusted odds ratio 2.7, 95% confidence interval 1.2 5.9; P < .02). Shoulder dystocia occurred in one of 19 vaginal deliveries with elective induction (5.3%) and in two of 79 with spontaneous labor (2.5%). CONCLUSION: Because elective induction of labor increased the cesarean rate and did not prevent shoulder dystocia, we conclude that mothers with macrosomic fetuses can safely be managed expectantly unless there is a medical indication for induction. PMID- 8459955 TI - Induction of labor and risk of sudden infant death syndrome. AB - OBJECTIVE: To investigate whether induction of labor is related to the occurrence of sudden infant death syndrome (SIDS) using a population-based, case-control study. METHODS: Cases comprised infants born between 1984-1988 in Washington state who died of SIDS according to their death certificate (ICD-9-CM 798.0) (N = 728). For comparison, we randomly selected a group of infants born in these same years who did not die of SIDS (N = 3021). Information regarding the pregnancy, labor, delivery, and condition of the newborn was obtained from the infants' birth certificates. RESULTS: Among the indications for induction that were examined, we found a slightly elevated risk of SIDS associated with advanced gestational age (greater than 41 completed menstrual weeks) (odds ratio [OR] 1.3, 95% confidence interval [CI] 1.0-1.8). A similar proportion of cases and controls had induced labors (OR 1.2, 95% CI 0.7-2.1). Although there was little or no apparent risk associated with induction among infants who had term gestations (37 41 completed menstrual weeks; OR 1.2, 95% CI 0.6-2.2), an increased risk was found among infants who had gestations of 42 weeks or greater (OR 3.0, 95% CI 0.7 12.5). We did not observe this trend with augmentation of labor. CONCLUSION: Our findings do not support an overall association between the methods used for induction of labor in the United States and the occurrence of SIDS. The elevated risk of SIDS observed in relation to induction of labor among infants who had post-term gestations raises the possibility that infants who do not spontaneously initiate labor may suffer some neuroregulatory or other abnormality involved in the pathogenesis of SIDS. PMID- 8459956 TI - Immediate postpartum curettage: accelerated recovery from severe preeclampsia. AB - OBJECTIVE: To investigate the ability of immediate postpartum curettage to accelerate maternal recovery from severe preeclampsia. METHODS: Thirty-two parturients with severe preeclampsia were randomly assigned to either undergo ultrasound-directed curettage following delivery or to have no curettage. RESULTS: Subjects who underwent immediate postpartum curettage had a significantly decreased mean arterial pressure at each 2-hour point for the first 24 hours compared with those who were not curetted (P < .0002). The mean urine output after uterine curettage was significantly greater during each 4-hour interval of the first 24 hours postpartum compared with controls (P < .0002). The platelet count increased in the curettage group from 12 to 24 hours following curettage, whereas controls exhibited a decrease in the platelet count from 12 to 24 hours (P < .0003). CONCLUSION: Immediate puerperal uterine curettage of the parturient with severe preeclampsia appears to accelerate disease recovery with no apparent adverse sequelae. PMID- 8459957 TI - Transvaginal duplex Doppler ultrasonography in bleeding patients suspected of having residual trophoblastic tissue. AB - OBJECTIVE: To evaluate the diagnostic accuracy and clinical usefulness of high resolution transvaginal duplex Doppler ultrasound in postpartum and post-abortion patients with excessive hemorrhage who are suspected of having residual trophoblast. METHODS: Forty-eight women with excessive hemorrhage referred for possible residual trophoblastic tissue were evaluated by transvaginal duplex Doppler ultrasonography. Based on two-dimensional imaging, the patients were divided prospectively into groups: women who had an empty uterus with a normal uterine cavity, those with a pure endometrial fluid collection and no echogenic foci, those who had a mixed endometrial fluid collection with foci of echogenicity, and those with intracavitary heterogeneous material with mixed echo patterns of fluid and solid components. In each group, Doppler studies were performed and the resistance index (RI) was calculated. The two-dimensional patterns and Doppler results were correlated with clinical and pathologic follow up. RESULTS: Twenty-eight subjects had a normal uterine cavity and seven had a pure endometrial fluid collection; all were treated conservatively and none showed later clinical evidence of residual trophoblastic tissue. In 13 women, residual trophoblast was strongly suggested from the images of two-dimensional ultrasonography: Five showed an endometrial fluid collection with some echogenic foci, and eight exhibited intracavitary mixed echogenic material. All underwent curettage, and residual trophoblastic tissue was found in ten of the 13. The mean (+/- standard deviation) RI to flow in the myometrial arteries was 0.54 +/- 0.15 in women without residual trophoblast and 0.35 +/- 0.1 in those with residual trophoblastic tissue (P < .01). CONCLUSION: Our experience suggests that transvaginal duplex Doppler ultrasonography is an effective noninvasive method for evaluating patients with excessive postpartum and post-abortion hemorrhage who are suspected of having residual trophoblastic tissue. Its use enhances the positive preoperative diagnosis of residual trophoblastic tissue and may reduce unnecessary curettage procedures. PMID- 8459958 TI - Do delayed childbearers face increased risks of adverse pregnancy outcomes after the first birth? AB - OBJECTIVE: To investigate whether the age-related risk of adverse pregnancy outcomes in the first birth persisted in the second birth, before and after adjusting for the influence of an adverse pregnancy outcome in the first birth and for other possible confounders. METHODS: Prospectively collected longitudinal data from the Swedish Medical Birth Registry (n = 210,735 women) were analyzed to contrast the effects of maternal age at the first birth on the risk of adverse pregnancy outcomes in the first and second successive births. RESULTS: Rates of adverse pregnancy outcomes were substantially higher in first than in second births. Compared with women aged 20-24, women aged 30-34 years had significantly higher odds ratios (ORs) of late fetal death (OR 1.4) and early neonatal death (OR 1.4) for the first but not for second births; women aged 35+ had a significantly higher OR of late fetal death (OR 2.2) for the first but not for second births. Women over 35 also had a significantly higher OR of early neonatal death for the first birth (OR 2.8) and less of an increase for second births (OR 1.8), a higher OR of low birth weight (LBW) for the first (OR 1.5) and second births (OR 1.6), and a higher OR of preterm birth for the first (OR 1.4) and second births (OR 1.7). Despite the strong tendency to repeat an adverse pregnancy outcome in second births, the age-related ORs did not change with adjustment for the previous pregnancy outcome. CONCLUSION: Women aged 30+ at their first births have increased risks of adverse pregnancy outcomes in first births. However, second births showed no age-related increase in late fetal death and a smaller increase in early neonatal death. Increased risks for LBW and preterm birth were similar for first and second births of delayed childbearers. PMID- 8459959 TI - Racial differences in oral glucose screening test results: establishing race specific criteria for abnormality in pregnancy. AB - OBJECTIVE: To determine whether the 1-hour glucose screening test threshold of 140 mg/dL yields similar results in identifying gravidas with gestational diabetes mellitus in different races and, if not, to establish consistent race specific thresholds. METHODS: Nine hundred twenty-one gravidas undergoing routine third-trimester glucose screening were categorized as white, black, Asian, or Filipino. Mean (+/- standard deviation) glucose screening test values, the proportions with results exceeding 140 mg/dL, and the positive predictive values for gestational diabetes mellitus were calculated by race. Race-specific thresholds were calculated by standardizing the percentile rank cutoff for test results in each group. RESULTS: Mean glucose screening test results differed significantly by race: blacks 116.4 +/- 31.6 mg/dL, whites 123.2 +/- 28.4 mg/dL, Filipinos 127.6 +/- 26.3 mg/dL, and Asians 134.7 +/- 25.0 mg/dL (P < .001). No significant difference was found between Hispanic and non-Hispanic whites (123.2 +/- 28.3 versus 123.5 +/- 28.5 mg/dL). Significant different proportions of gravidas exceeded the 140-mg/dL threshold by race: blacks 17.5%, whites 27.4%, Filipinos 31.3%, and Asians 40.6%. The proportions with results above 140 mg/dL who had abnormal 3-hour glucose tolerance tests also varied markedly by race: blacks 42.9%, whites 17.3%, Filipinos 11.5%, and Asians 11.5%. Adjusted screening test thresholds, calculated for each race to establish consistency of the screening test, were 130 mg/dL for blacks, 140 mg/dL for whites, 145 mg/dL for Filipinos, and 150 mg/dL for Asians. CONCLUSION: Race-specific glucose screening test thresholds should be used to ensure consistency in properly identifying gravidas at risk for gestational diabetes mellitus. PMID- 8459960 TI - Weight gain in women with gestational diabetes. AB - OBJECTIVE: To evaluate weight gain during pregnancy in women with gestational diabetes, and to determine whether there was a stronger or weaker correlation of maternal weight gain with neonatal birth weight in women with gestational diabetes as compared with a control group. METHODS: At delivery, 78 women with gestational diabetes and 312 control subjects were evaluated and classified according to pregravid weight for height (underweight, average weight, and overweight). Weight gain during pregnancy and neonatal birth weight in the women with gestational diabetes and in the control group were compared using analysis of covariance, controlling for selected covariables. A weight gain curve for each patient was generated to assess the rate of weight gain during early, middle, and late gestation. Linear regression analysis was used to correlate maternal weight gain and birth weight. RESULTS: Weight gain was 2.5 kg less in the women with gestational diabetes as compared with the controls (P = .0006). When adjusted for pregravid weight, maternal age, and gestational age at delivery, only underweight women with gestational diabetes persisted in having significantly less weight gain as compared with the control subjects (P = .035). There were no significant differences in infant birth weight between any gestational diabetes and control weight categories. The rate of weight gain was decreased in over-weight women with gestational diabetes versus control subjects in late pregnancy (P = .05). There was a significant correlation between maternal weight gain and birth weight in underweight (r = 0.46, P = .0001) and average-weight (r = 0.17, P = .02) control women but not in overweight controls or in any patients with gestational diabetes. CONCLUSION: Weight gain in women with gestational diabetes is less than in control patients, primarily because of greater pregravid weight, and does not correlate with neonatal birth weight. PMID- 8459962 TI - Cigarette smoking and preeclampsia. AB - OBJECTIVE: To examine the relationship between cigarette smoking during pregnancy and the development of preeclampsia. METHODS: A case-control study compared the smoking histories of 110 nulliparous preeclamptic women and 115 healthy nulliparas aged 15-35 years who delivered at North Carolina Memorial Hospital. RESULTS: Unconditioned logistic regression relating smoking during pregnancy to preeclampsia yielded an odds ratio of 0.71 (95% confidence interval 0.33-1.50) when adjusting for working during pregnancy, alcohol use, medication use, contraceptive choices with the father of the index pregnancy, and family history of preeclampsia. There was no evidence of a dose-response effect of reduced risk for heavier smokers. CONCLUSIONS: Despite major methodologic improvements from previous studies, including rigorous diagnostic criteria for preeclampsia, a negative, non-statistically significant association persisted between cigarette smoking during pregnancy and preeclampsia, similar in magnitude to that of previous reports. PMID- 8459961 TI - Prenatal weight gain, term birth weight, and fetal growth retardation among high risk multiparous black and white women. AB - OBJECTIVE: To examine the association of prenatal weight gain below, within, and above the Institute of Medicine guidelines with birth weight and fetal growth restriction (FGR) among low-income, high-risk black and white women. METHODS: Eight hundred three black and 365 white women were grouped by pregravid body mass index (BMI): low (below 19.8), normal (19.8-26), high (above 26-29), and very high (above 29). The impact of maternal weight gain on birth weight and race specific FGR was determined while controlling for sociodemographic and reproductive variables and for time between last weight observation and delivery. RESULTS: One-third of both black and white women failed to achieve the Institute of Medicine minimum recommended gain for pregravid BMI. More women with low BMI gained less than the recommended weight as compared with those having normal, high, or very high BMI. Nonobese black women (BMI 29 or below) delivered fewer infants with FGR as weight gain increased from below the recommended range (17.9% FGR) to within (10.3% FGR) or above (3.8% FGR) the range; corresponding data for nonobese white women were 20.9, 19.1, and 10.5% FGR, respectively. Obese black women (BMI above 29) also delivered fewer infants with FGR (4.2%) when they exceeded the minimum gain (6 kg) than did white women (11.8%). When analysis of covariance was used to adjust mean birth weight, black women in each pregravid BMI category delivered increasingly larger infants (P < or = .01 for each category) as they met or exceeded the guidelines; among white women this trend was attenuated. CONCLUSION: These observations support the Institute of Medicine suggestion that black women strive for prenatal weight gain at the upper end of the recommended range for pregravid BMI. PMID- 8459963 TI - Cocaine intoxication presenting as preeclampsia and eclampsia. AB - OBJECTIVE: To relate the clinical presentation of acute cocaine intoxication in the third trimester to preeclampsia and eclampsia. METHODS: Eleven women presented to Long Beach Memorial Women's Hospital and the University of California, Irvine Medical Center with hypertension and clinical symptoms of headache, blurred vision, abdominal pain, or seizures in the third trimester of pregnancy. Each had a positive urine drug screen for cocaine. The laboratory evaluation for preeclampsia included a complete blood count, platelet count, uric acid, aspartate aminotransferase, alanine aminotransferase, creatinine, and urine for protein content. RESULTS: All women had a diastolic blood pressure of at least 90 mmHg, which returned to the normal range 45-90 minutes after admission. Each presented with one or more symptoms associated with preeclampsia, which ultimately improved as the drug wore off. In addition, all laboratory evaluations for preeclampsia were negative. CONCLUSION: If a patient presents in the third trimester with hypertension and clinical symptoms of preeclampsia that rapidly improve shortly after admission, cocaine intoxication should be considered as the possible source. PMID- 8459964 TI - The effect of fetal acoustic stimulation on fetal swallowing and amniotic fluid index. AB - OBJECTIVE: To determine the effect of fetal acoustic stimulation on fetal swallowing and amniotic fluid (AF) index in an attempt to understand the potential mechanism for fetal compromise following fetal acoustic stimulation. METHODS: Fetal swallowing movements and AF index were assessed in 90 full-term fetuses before and after fetal acoustic stimulation. Fetal swallowing movements were identified on a video monitor and measured in terms of the percentage of time they occurred during 30 minutes of observation. The fetal heart rate was recorded 30 minutes before and 30 minutes after fetal acoustic stimulation. RESULTS: The mean (+/- standard deviation) percentage of time spent by the fetus in swallowing increased from 16.1 +/- 6% before to 44.3 +/- 10.3% after stimulation (P < .005). The AF index decreased from 14.6 +/- 8.4 cm before acoustic stimulation to 12.8 +/- 6.8 cm afterward (not statistically significant). Seven of 17 patients (41%) with borderline AF indexes developed oligohydramnios after the fetal acoustic stimulation; two of these demonstrated persistent variable decelerations that required obstetric intervention. CONCLUSIONS: Fetal acoustic stimulation is associated with increased fetal swallowing activity, which can lead to diminution of AF volume. The AF index should be assessed in fetuses before acoustic stimulation and if the volume is low, acoustic stimulation should be used with extreme caution. PMID- 8459965 TI - Cigarette smoking during pregnancy: acute effects on uterine flow velocity waveforms. AB - OBJECTIVE: To determine the acute effects of smoking during pregnancy on selected characteristics of the flow velocity waveform of the uterine artery. METHODS: We studied 19 chronic smokers at a mean (+/- standard error) gestational age of 28 +/- 1 weeks. After informed consent was given, the uterine artery was located using ultrasound imaging with color flow mapping. The characteristic waveform was imaged by pulsed Doppler ultrasonography. Maternal heart rate and blood pressure and the systolic-diastolic ratio (S/D) and resistance index of the uterine artery were measured before (-10 and -1 minutes), during (+5 and +10 minutes), and after (+20 and +30 minutes) smoking two standard cigarettes in succession. RESULTS: Maternal heart rate increased 27%, systolic blood pressure increased 8%, and diastolic blood pressure increased 19% with smoking (P < .001). The uterine artery S/D and resistance index decreased from 2.33 to 2.02 and from 0.55 to 0.49, respectively (P < .001). CONCLUSION: The acute effects of smoking on maternal systemic hemodynamics probably influence the flow velocity waveform of the uterine artery and preclude any definitive interpretation of acute changes in downstream resistance. PMID- 8459966 TI - Placental microvascular changes in twin pregnancies with abnormal umbilical artery waveforms. AB - OBJECTIVE: To determine whether there is a relationship between umbilical artery Doppler waveforms and placental histology in twin pregnancies. METHODS: The placental vasculature was examined histologically in 41 cases of twin pregnancy in women who had undergone antenatal Doppler umbilical artery waveform analysis. RESULTS: Those fetuses with abnormal systolic-diastolic ratios (S/Ds) showed a reduction in the placental tertiary stem villi arterial vessels compared with fetuses with normal S/Ds. The mean count of small arterial vessels (diameter less than 90 mu) in the placentas from cases with normal S/Ds (below the 95th percentile) was 5.6, whereas the mean arterial count for those with high S/Ds (above the 99th percentile) was 3.9 (P = .039). CONCLUSIONS: In twin pregnancies complicated by placental insufficiency, there is microvascular disease restricted to the placenta of the affected fetus. This suggests that the placental vascular lesion originates in the fetal circulation rather than in the uteroplacental vasculature. PMID- 8459967 TI - Fetal renal artery flow velocity waveforms in normal pregnancies and pregnancies complicated by polyhydramnios and oligohydramnios. AB - OBJECTIVES: To determine 1) flow velocity waveform patterns in the fetal renal artery in normal pregnancies and pregnancies complicated by polyhydramnios or oligohydramnios, and 2) fetal urine output in twin gestations complicated by polyhydramnios-oligohydramnios syndrome. METHODS: Doppler waveforms were recorded in 121 normal fetuses, ten fetuses with oligohydramnios, ten with polyhydramnios, and eight sets of diamnionic twins with polyhydramnios in one gestational sac and oligohydramnios in the second sac. In the twins, the fetal urine output was also estimated. RESULTS: The pulsatility index (PI) of the renal artery in normal fetuses decreased linearly with advancing gestation. Abnormal renal artery PIs were found in four fetuses with oligohydramnios. The values in the singleton pregnancies complicated by polyhydramnios were in the range of normality for our reference limits for gestation. The PI of the renal artery in the twins with polyhydramnios was significantly lower than that from the twins with oligohydramnios. The urine output was significantly higher in twins with polyhydramnios than in twins with oligohydramnios. CONCLUSIONS: Normal pregnancies are associated with changes in the renal artery flow velocity waveforms. In fetuses with oligohydramnios, the worst fetal outcome seems to be associated with abnormal renal artery flow velocity waveforms. In fetuses with polyhydramnios, no abnormal renal artery flow velocity waveforms were found. Changes in renal perfusion influence urine output in twin gestations complicated by polyhydramnios-oligohydramnios. PMID- 8459968 TI - The relationship between the ultrasonographic diagnosis of innocent amniotic band development and pregnancy outcomes. AB - OBJECTIVE: To determine the importance of amniotic bands diagnosed ultrasonographically and their relationship to pregnancy outcome. METHODS: We reviewed retrospectively the ultrasonographic records at State University of New York Health Science Center at Brooklyn and Kings County Hospital Center, identifying 25 cases of amniotic band diagnosed during 1986-1990. Cases were compared with 50 controls who had ultrasound evaluation at the same gestational age. Outcomes studied included fetal anomalies, obstetric factors or complications, pregnancy outcome, and maternal factors that may have predisposed to the formation of bands. RESULTS: All cases had unrestricted fetal movement on the index sonogram. No fetal abnormalities were observed in either the case or control series. The groups were not significantly different in terms of maternal risk factors, but significant differences were found for delivery at less than 37 weeks and birth weight less than 2500 g. CONCLUSION: Ultrasonographic diagnosis of an amniotic band in connection with sonographic findings of normal fetal anatomy may be a risk factor for preterm delivery and low birth weight. No association between amniotic band development and fetal anomalies was observed. PMID- 8459969 TI - The role of velamentous cord insertion in the etiology of twin-twin transfusion syndrome. AB - OBJECTIVE: To evaluate the prevalence of velamentous cord insertion in twin-twin transfusion using the hypothesis that such insertions may contribute to the etiology of the condition. METHODS: All cases of placentas referred for pathologic evaluation at the University of California at San Francisco from 1984 1992 were reviewed for the citation of diamniotic-monochorionic placentation, including the presence of velamentous cord insertions. Maternal and infant records were studied for findings consistent with twin-twin transfusion syndrome. RESULTS: Thirty-eight cases of monochorionic-diamniotic twins were identified, 11 of which showed twin-twin transfusion syndrome. The prevalence of velamentous cord insertion in the transfusion syndrome subset was 63.6%, compared with 18.5% in those without (significant difference at P < .01). Twin-twin transfusion syndrome pregnancies with velamentous insertions were delivered at a significantly earlier gestational age; they also had fewer surviving infants and were more likely to have been treated prenatally than transfusion syndrome pregnancies without velamentous insertion, although these latter two findings were not significantly different. CONCLUSIONS: Velamentous cord insertions are more common in twin-twin transfusion syndrome pregnancies and may contribute to the development of profound disparity in fluid volume because the membranously inserted cord can be easily compressed, reducing blood flow to one twin. Large volume amniocentesis may reduce this compressive force on the cord insertion, thus explaining the success of this mode of intervention. PMID- 8459970 TI - Cord blood erythropoietin in relation to different markers of fetal hypoxia. AB - OBJECTIVE: To investigate the relationship between erythropoietin concentration in umbilical venous blood and clinical signs of fetal hypoxia. METHODS: We measured erythropoietin concentrations in umbilical venous blood from 200 consecutively born neonates using an enzyme-linked immunosorbent assay (ELISA) with two monoclonal antibodies. Results were available within 6 hours. Inter assay variation was 8.5% and the mean intra-assay variation was 14.2%. RESULTS: Using a multiple regression analysis, we found that the erythropoietin concentration correlated significantly (P < .01) with fetal growth retardation and umbilical acidosis but not with gestational age, meconium-stained amniotic fluid (AF), abnormal fetal heart rate (FHR) pattern, or Apgar score at 5 minutes. Median erythropoietin concentrations were 25.1 mU/mL in infants with no risk factors or complications during pregnancy and delivery (n = 19), 25.8 mU/mL after complicated pregnancy (n = 95), 50.6 mU/mL with meconium-stained AF (n = 12), 44.7 mU/mL with abnormal FHR pattern (n = 40), 47.8 mU/mL with both stained AF and abnormal FHR pattern (n = 10), and 72.6 mU/mL with umbilical acidosis (n = 24). The median erythropoietin concentration increased significantly with decreasing pH and with increasing base deficit in umbilical arterial blood. The erythropoietin concentration in umbilical venous blood (cutoff value 50 mU/mL) discriminated between infants with no clinical signs of fetal hypoxia and those with umbilical acidosis with a sensitivity of 75% and a specificity of 90%. CONCLUSIONS: Elevated erythropoietin concentrations in umbilical venous blood indicate prolonged fetal hypoxia. The ELISA technique might be a useful tool for determining the exact time course of erythropoietin concentrations in fetal hypoxia. PMID- 8459971 TI - Effects of sodium etidronate in combination with low-dose norethindrone in patients administered a long-acting GnRH agonist: a preliminary report. AB - OBJECTIVE: To assess the efficacy of combining sodium etidronate with low doses of the 19-nor-testosterone progestin norethindrone or using high doses of norethindrone alone as prophylaxis against the vasomotor instability and bone density loss induced by GnRH agonists alone. METHODS: Eleven patients enrolled in this randomized study received the long-acting GnRH agonist leuprolide acetate 3.75 mg intramuscularly every 4 weeks for 24 weeks. Six patients (group I) self administered sodium etidronate 400 mg/day orally for 14 days followed by calcium carbonate 500 mg/day orally for the next 42 days during three 56-day cycles. This regimen was supplemented by norethindrone 2.5 mg/day orally. Five patients (group II) self-administered norethindrone 10 mg/day orally. Two sets of controls were used. Group III consisted of ten previously reported patients who received the same GnRH agonist only. Group IV comprised 12 regularly cycling untreated controls. Bone mineral density, vasomotor symptoms, circulating estrogens, and lipids were assessed serially. RESULTS: The significant vasomotor instability (P < .01) and bone mineral density loss (-4.8 +/- 0.9%; P < .05) experienced by patients in group III was prevented in those in groups I and II despite maintenance of a persistent hypoestrogenic state. Bone density changes in groups I and II were similar to those in untreated controls (group IV). Persistent decreases in high-density lipoprotein (HDL) cholesterol (P = .005) and increases in the low-density lipoprotein-to-HDL ratio (P < .05) were noted only in group II patients receiving supplemental high-dose norethindrone. CONCLUSION: These preliminary data suggest that the addition of cyclic sodium etidronate in combination with low-dose norethindrone to GnRH agonists is an effective means of ameliorating the hypoestrogenic side effects induced by GnRH agonist alone. PMID- 8459972 TI - GnRH agonist exposure during the first trimester of pregnancy. AB - OBJECTIVE: To evaluate pregnancy outcome in infertility patients with unrecognized exposure to a GnRH agonist in the first trimester. METHODS: Five women were given GnRH agonist before controlled ovarian hyperstimulation for in vitro fertilization cycles. The medication was administered in a dose of 0.5 mg/day, with drug exposure beginning on cycle day 21. The duration of exposure in all patients was 14-21 days. Thus, all five women received the medication at 3-6 weeks' estimated gestational age by menstrual dating. Pregnancy tests were not performed before the first injection of the GnRH agonist. RESULTS: Three of the five pregnancies progressed to term without complication, and normal healthy infants were delivered. Missed abortion occurred in one pregnancy, and another ended in induced abortion at 13 weeks because of trisomy 18. CONCLUSIONS: This experience suggests that despite manipulation of the hypothalamic-pituitary ovarian axis by administration of GnRH agonist in the first trimester of pregnancy, normal pregnancies can result. Pregnancies in these patients should not be terminated because of drug exposure alone. PMID- 8459973 TI - Perioperative complications arising after transvaginal oocyte retrieval. AB - OBJECTIVE: To determine the incidence of perioperative morbidity in patients undergoing transvaginal oocyte retrieval and to identify those patients at greatest risk for complications. METHODS: A retrospective analysis was performed on 674 patients of reproductive age who underwent transvaginal retrieval of oocytes for assisted reproduction technologies during a 3-year period. All procedures were performed by surgeons with extensive experience with transvaginal retrieval. Patients were entered into the program with a primary diagnosis of unexplained infertility (16%), endometriosis (32%), pelvic adhesions and/or tubal occlusion (38%), or infertility from male or immunologic factors (14%). RESULTS: Of the 674 patients studied, ten (1.5%) required hospital admission because of perioperative complications. Nine of these patients needed intravenous antibiotics and one required admission and observation for an expanding broad ligament hematoma. Six of nine women admitted for antibiotic therapy had a history of extensive pelvic adhesions with or without a history of salpingitis. Five of nine patients had a history of salpingitis. In addition, two patients experienced impressive vaginal arterial bleeding during the procedure. CONCLUSION: This study suggests that transvaginal retrieval may not be as innocuous as is often expressed and that the primary factor predisposing to perioperative morbidity is a history of previous pelvic inflammatory disease and/or adnexal adhesions. PMID- 8459974 TI - Factors influencing spontaneous abortion, dyspareunia, dysmenorrhea, and pelvic pain. AB - OBJECTIVE: To investigate the following: 1) the influence of pelvic inflammatory disease, postabortal complications, previous induced abortions, and age on the rate of subsequent spontaneous abortion; and 2) the influence of pelvic inflammatory disease, postabortal complications, previous induced abortions, previous spontaneous abortions, age, and parity on the rates of dyspareunia, dysmenorrhea, and chronic pelvic pain. METHODS: The study population consisted of a cohort of 1229 pregnant women, of whom 868 were referred for delivery and 361 for first-trimester abortion. Outcome measures examined were spontaneous abortion and the occurrence of dyspareunia, dysmenorrhea, and chronic pelvic pain. RESULTS: In 839 women without previous induced abortion, a history of pelvic inflammatory disease was associated with an increased risk of spontaneous abortion (odds ratio 1.55, 95% confidence interval [CI] 1.03-2.33); women above age 33 had a lower risk of spontaneous abortion (odds ratio 0.53, 95% CI 0.30 0.96). In 382 women with previous induced abortion, the influence of age on the rate of spontaneous abortion was continuous so that an increase of 1 year of age reduced the risk of spontaneous abortion by 0.91 (95% CI 0.85-0.96). Women with any previous pelvic inflammatory disease, when compared with those without, more often had dyspareunia (14 versus 3%; odds ratio 3.87, 95% CI 2.35-6.37) and chronic pelvic pain (6 versus 0.4%; odds ratio 13.07, 95% CI 10.09-16.04). Age was inversely associated with the incidence of dysmenorrhea (odds ratio 0.94, 95% CI 0.91-0.97). CONCLUSION: Pelvic inflammatory disease is associated with later spontaneous abortion, whereas age correlates inversely with the rate of spontaneous abortion. Spontaneous and postabortal pelvic inflammatory diseases carry significantly elevated risks of dyspareunia and chronic pelvic pain. PMID- 8459975 TI - Short hospital stay for gynecologic reconstructive surgery via laparotomy. AB - OBJECTIVE: To evaluate the short hospital stay for different gynecologic reconstructive procedures performed by laparotomy. METHODS: Two hundred twelve patients who had tubal reanastomosis, 124 who had salpingoneostomy, and 148 who had myomectomy were studied retrospectively. The study evaluated pregnancy rates, adhesion formation, discomfort, and complications in each group. RESULTS: Pregnancy rates for the reanastomosis, salpingoneostomy, and myomectomy patients were 72, 34, and 63%, respectively. Twenty-three percent of salpingoneostomy patients developed flimsy periadnexal adhesions, whereas only 9% in the myomectomy group developed flimsy pelvic adhesions. No complications occurred in any of the three groups. Less than 1% of patients in the two tuboplasty groups complained of minimal abdominal discomfort before discharge, and 4% had similar complaints in the myomectomy group. CONCLUSION: Patients who have gynecologic reconstructive surgery can be discharged within 24 hours after the procedure with an excellent outcome. PMID- 8459976 TI - Vaginal douching as a risk factor for acute pelvic inflammatory disease. AB - OBJECTIVE: To conduct a population-based evaluation of vaginal douching as a risk factor for acute pelvic inflammatory disease (PID), emphasizing timing, frequency, and reasons for douching. METHODS: A population-based case-control study was conducted at Group Health Cooperative of Puget Sound, a staff-model health maintenance organization located in western Washington state. The cases (N = 131) were women 18-40 years of age who experienced a first episode of clinically diagnosed acute PID. Both hospitalized and ambulatory-care patients were identified. Medical records were reviewed for clinical inclusion criteria and for additional evidence of inflammation/infection. Controls (N = 294) were chosen from a population-based series of randomly selected women from a concurrent Group Health study of ectopic pregnancy. Of the women identified, 72.4% of cases and 73.4% of controls agreed to participate. RESULTS: Relative to women who reported never having douched, women who douched during the previous 3 months had a risk of PID of 2.1 after controlling for other measured risk factors (95% confidence interval [CI] 1.2-3.9). Women who douched at least once a week had a higher estimated risk (odds ratio 3.9, 95% CI 1.4-10.9) than those who douched less often (odds ratio 1.8, 95% CI 1.0-3.4). The risk was highest in the small group of women who gave infection as the reason for douching (odds ratio 7.9, 95% CI 2.6-24.2). However, exclusion of this group did not eliminate the association among the remaining women (odds ratio 3.0, 95% CI 1.0-9.1 for douching at least once a week). CONCLUSION: These population-based data lend added support to the hypothesis that vaginal douching can predispose a woman to PID. PMID- 8459977 TI - Operating room personnel morbidity from carbon dioxide laser use during preceptored surgery. AB - OBJECTIVE: To determine the extent of laser-induced morbidity away from the operative site during the preceptor phase of laser credentialing in our institution. METHODS: All laser surgeries performed from June 1, 1990 through May 31, 1991 and preceptored by one of the authors (MB) were included in the study. All of the surgeries were performed by a resident or attending physician seeking laser privileges in our institution. During that time, 141 such cases were performed. RESULTS: In 13 of 141 cases (9%), there were injuries unrelated to the surgical procedure itself to either the patient or operating personnel. There were nine accidents associated with laser use during 42 laparotomy procedures (21%) and four accidents at the time of 44 vulvar surgeries (9%). There were no accidents during laparoscopic or colposcopic surgery of the vagina or cervix. CONCLUSIONS: Despite extensive training requirements before use of the CO2 laser, accidents did occur. Operating room safety requirements should be a high priority to minimize morbidity. We report our experience with intraoperative morbidity caused by surgeons' errors and present recommendations to limit further complications. PMID- 8459978 TI - Should all pregnant patients be offered prenatal diagnosis regardless of age? AB - OBJECTIVE: To assess the acceptance of prenatal genetic diagnosis by patients younger than 35 years old who are therefore not yet at great risk for non disjunction trisomies based on maternal age. METHODS: The patients were counseled regarding the following: 1) the age-related risk of chromosomal abnormalities, 2) the procedure-related risk of fetal loss, 3) clinical implications of chromosomal abnormalities, 4) the need for complete counseling by a certified genetic counselor, and 5) the patient expense of $600-1200 if third-party reimbursement was not available. Patients were recruited from the private practice of the senior author at the New York Hospital--Cornell Medical Center. Five hundred ninety-one patients were offered prenatal genetic diagnosis. The outcome measure was the patient's decision to undergo prenatal diagnosis even though the risk of a non-disjunction trisomy was expected to be low based on maternal age. Amniocentesis was performed in 128 patients and chorionic villus sampling in five. RESULTS: One hundred thirty-three patients (22.5%) chose prenatal diagnosis. Karyotype was obtained in 131 procedures, but two were unsuccessful. One of the 131 karyotypes was abnormal and the patient chose to terminate the pregnancy. CONCLUSIONS: The data showed the following: 1) Inappropriate influence of patients by the health provider was not evident; 2) routine offering of genetic diagnosis enhanced the autonomy of pregnant women; 3) the potential increase in the loss of pregnancies that accompanies this practice is ethically justified; and 4) there are no compelling cost-benefit objections to such a practice. PMID- 8459979 TI - Lamellar body counts for rapid fetal lung maturity testing. AB - OBJECTIVE: To evaluate amniotic fluid lamellar body counting as a fetal lung maturity test. Lamellar body particles can be rapidly counted using the platelet channel of most blood cell analyzers. METHODS: We conducted a 3-year prospective clinical outcome study. During the interval under study, outcomes of 247 neonates were used to evaluate the test; 28 neonates developed respiratory distress syndrome (RDS). Lecithin-sphingomyelin ratio (L/S) was available for 187 cases. RESULTS: All cases of RDS had lamellar body counts of 55,000/microL or less and L/S of 2.2 or less; 59% of cases with no RDS had counts greater than 55,000/microL and 70% of normal cases had L/S higher than 2.2. CONCLUSION: Use of lamellar body counts is justified as a rapid screening test to predict fetal lung maturity. Immature results should be followed by a more specific test such as L/S. PMID- 8459980 TI - Statistically speaking. PMID- 8459981 TI - Commercialization of clinical genetic laboratory services: in whose best interest? AB - Major technological advances in human genetics have rapidly reached clinical practice. Presymptomatic, predictive, prenatal, and carrier detection tests are now commonplace for an increasing number of monogenic and other disorders. Sophisticated laboratory studies with complex results require knowledge of clinical genetics for correct interpretation. There is a clear imperative to have clinical genetics specialist physicians involved with communications, interpretations, and consultations about these laboratory reports. Notwithstanding such appropriate requirements, commercial laboratories now deliver complex genetic laboratory reports directly to physicians unprepared for necessary interpretations. Guidance from commercial operations is frequently provided by non-physicians by telephone. Moreover, such facilities market their own unproven, non-peer-reviewed diagnostic tests, false claims included, directly to physicians. Beguiled by the speed with which results are obtained, harried obstetricians not skilled in critical technical analysis of such new tests have quickly fallen prey to sales pitches. The best and most comprehensive genetic care is usually available from an academic-based laboratory within a teaching medical center. Obstetricians have an added liability burden if they are not allied with a genetics center upon whom they can call for reliable results and appropriate guidance. PMID- 8459982 TI - Preliminary experience with intrapartum fetal pulse oximetry in humans. AB - Electronic fetal heart rate (FHR) monitoring is commonly used to assess fetal well-being during labor. Nonreassuring patterns in many cases are associated with normal fetal acid-base condition, leading to unnecessary operative intervention. Fetal pulse oximetry has several potential advantages over FHR monitoring because it assesses not only pulse, but also arterial oxygen saturation and tissue perfusion. We describe our preliminary experience with the Nellcor N-400 Fetal Oxygen Saturation Monitor and FS-10 Oxisensor in 73 subjects during active labor at term. The mean (+/- standard deviation) duration of monitoring was 161.4 +/- 106.0 minutes, with sensor contact achieved 67.3 +/- 22.5% of the time during labor. Data were successfully recorded in all patients, with a reliable signal obtained 50.1 +/- 21.6% of the time during labor. The mean fetal oxygen saturation was 57.9 +/- 10.0%. The potential for research and clinical applications appears promising with further sensor and monitor development. PMID- 8459983 TI - Use of a DNA probe for the rapid detection of group B streptococci in obstetric patients. AB - OBJECTIVE: To determine the accuracy of a DNA probe as a rapid diagnostic test for detecting colonization of the female genital tract by group B streptococci during pregnancy. METHODS: Two rayon-tipped applicators were used to collect secretions from the posterior vaginal wall of 440 pregnant women. One of the applicators was inoculated into selective Todd-Hewitt broth and used as the reference standard for identification of group B streptococci. The other applicator was used for analysis with the DNA probe, preceded by either 2.5 hours of incubation for the initial 75 patients, or 3.5 hours' incubation for the remaining women. Following hybridization with an acridinium-labeled probe, chemiluminescence was measured with a luminometer. RESULTS: The prevalence of positive cultures was 20%. For the initial 75 patients whose cultures were amplified by incubation for 2.5 hours, the DNA probe had a sensitivity of 44%, specificity 94%, positive predictive value 79%, and negative predictive value 77%. For the cultures that were incubated for 3.5 hours, respective values were 71, 90, 61, and 94%. All vaginal specimens that had an average initial cell count of 1.5 x 10(3) cells/mL were accurately detected by the probe after 3.5 hours' growth amplification. False-positive results occurred primarily when the specimens were grossly contaminated with blood (26 of 39). The mean time required to perform the assay, including 3.5 hours of growth amplification, was 4.3 hours. CONCLUSIONS: The DNA probe demonstrated good overall sensitivity and gave no false-negative results when group B streptococci were present in concentrations of 1 x 10(4) cells/mL or greater. Sensitivity improved significantly with 3.5 hours' growth amplification as compared with 2.5 hours (P < .05), reflecting better identification of lightly colonized patients. PMID- 8459984 TI - Meta-analysis of cisplatin, doxorubicin, and cyclophosphamide versus cisplatin and cyclophosphamide chemotherapy of ovarian carcinoma. PMID- 8459985 TI - Future trends in cancer treatment and emesis control. AB - The treatment of cancer patients has improved over the last few years for a variety of reasons. These include improvements in diagnosis, more potent chemotherapeutic drugs and the introduction of new ways of containing or eliminating cancers by the use of multi-modality treatment regimens often facilitated by the use of chemoprotective agents. Cancer patients have also benefited from an increased awareness of their needs, with health care professionals paying attention to toxicities of treatment and optimising treatment schedules to combine the best possible medical outcome with patient comfort and acceptability of treatment. Thus not all the advances seen in the management of cancer patients have relied upon the introduction of novel anti tumour agents; important advances have been made by the optimal use of existing drugs, the revision of treatment schedules and better control of the side effects of treatment. One of the more distressing side effects of cancer chemotherapy, having a profound effect on its acceptability to patients, is nausea and vomiting. The introduction over the last 3 years, of ondansetron, the first generally available 5-HT3 receptor antagonist, has had beneficial effects on the management of patients. Through improvements in anti-emetic control ondansetron has provided a better quality of life and is now beginning to impact on the design and administration of conventional chemotherapy treatment schedules. This paper reviews the changes that have been seen with the use of ondansetron and makes several suggestions about areas where clinicians might find a beneficial role for 5-HT3 receptor antagonists. PMID- 8459986 TI - Ondansetron plus dexamethasone compared to the 'standard' metoclopramide combination. AB - This paper describes a multicentre, double-blind, parallel group study which compared ondansetron (0.15 mg/kg i.v. x 3) plus dexamethasone (20 mg i.v.) with metoclopramide (3 mg/kg i.v. x 2) plus dexamethasone (20 mg i.v.) and diphenhydramine (50 mg i.v.) for the prevention of cisplatin-induced emesis and nausea. Two hundred and eighty-nine consecutive patients receiving chemotherapy containing cisplatin at doses > or = 50 mg/m2 entered the study and 267 patients were evaluable for efficacy. The ondansetron regimen was significantly superior compared with the metoclopramide regimen in the control of acute emesis and nausea. Ondansetron plus dexamethasone provided complete protection against retching and vomiting in 79% of patients compared with 59% of patients given the metoclopramide combination (p < 0.002). Similarly ondansetron plus dexamethasone completely prevented nausea in 77% of patients, whereas the metoclopramide combination protected 66% of patients (p < 0.051). Success (no nausea and no emesis) was afforded to 69% of those patients given ondansetron plus dexamethasone as opposed to 50% of patients given the metoclopramide combination (p < 0.003). From day 2-4 all patients received the same anti-emetic regimen of oral metoclopramide and intramuscular dexamethasone. Significantly fewer patients who had received the ondansetron regimen on day 1 vomited on days 2 and 3 compared with those who had received the triple drug combination (84-86 and 68 71%, respectively, p < 0.006). Nausea was also better controlled in this group on day 2. On subsequent cisplatin cycles, the incidence of acute vomiting rose to 53% in those patients given the metoclopramide regimen, but remained low (26%) in the group treated with ondansetron plus dexamethasone. Patients receiving the metoclopramide regimen had significantly more sedation than patients receiving ondansetron plus dexamethasone (12 vs. 2%; p < 0.005). Extrapyramidal reactions were only observed in metoclopramide-treated patients (3%). The results of this study suggest that ondansetron plus dexamethasone is a more effective and better tolerated anti-emetic regimen compared with metoclopramide plus dexamethasone and diphenhydramine for the prevention of acute cisplatin-induced emesis. PMID- 8459987 TI - Role of ondansetron plus dexamethasone in fractionated chemotherapy. AB - This randomised, double-blind, parallel-group study was carried out to compare the efficacy and safety profile of ondansetron plus dexamethasone and metoclopramide plus dexamethasone in patients receiving fractionated cisplatin (20-25 mg/m2/day) chemotherapy for the treatment of testicular cancer. An interim analysis of 95 patients showed that the ondansetron regimen was significantly superior compared to the metoclopramide regimen (p < 0.001). According to the study protocol the study was terminated at this stage. At the time the decision to stop the study was taken, a total of 113 patients had been enrolled and were evaluable on an 'intention to treat' basis. Fifty-six of these had received ondansetron (32 mg i.v. single dose/day) plus dexamethasone (20 mg i.v. single dose/day) and 57 were given metoclopramide (2 mg/kg or 1 mg/kg i.v. twice a day) plus dexamethasone (20 mg i.v. single dose/day). The ondansetron regimen was significantly superior in the control of emesis and nausea. Seventy-one percent of patients experienced 2 or fewer emetic episodes over the entire 5-day study period compared with 26% of patients given metoclopramide (p < 0.001). Seventy nine percent of patients in the ondansetron group experienced 'none' or only 'mild' nausea compared with 39% of patients in the metoclopramide group (p < 0.001). The dose of metoclopramide had to be reduced during the study from 2 mg/kg i.v. twice daily to 1 mg/kg i.v. twice daily because 4 of the first 8 patients randomised to this treatment experienced extrapyramidal reactions. Ondansetron was well tolerated and it did not induce any extrapyramidal reactions. The results of this study show that ondansetron plus dexamethasone represents a very effective treatment option for patients receiving fractionated cisplatin chemotherapy for testicular cancer. PMID- 8459988 TI - A review of ondansetron in the management of radiotherapy-induced emesis. AB - This paper reviews experience with ondansetron in radiotherapy-induced emesis. The efficacy of ondansetron is assessed following a number of different radiotherapy regimens: single-dose radiotherapy, fractionated radiotherapy, total body irradiation (TBI) and hemi-body irradiation. In single-dose radiation induced emesis, ondansetron (8 mg orally 3 times daily) provided superior anti emetic control compared with metoclopramide (10 mg orally 3 times daily): 92 and 46% of patients, respectively, experienced complete control of emesis (0 emetic episodes) in the first 24 h following treatment (p < 0.001). Similarly, ondansetron (8 mg orally 3 times daily) was significantly (p < 0.001) more effective than prochlorperazine (10 mg orally 3 times daily) with 59 and 35% of patients, respectively, achieving complete control of emesis on the 'worst day' of a fractionated radiotherapy regimen (up to 20 fractions). Two studies evaluating the efficacy of ondansetron in TBI-induced emesis have demonstrated that ondansetron is effective in paediatric and adult patients receiving chemotherapy and TBI prior to bone marrow transplantation. In these studies, 57 81% of patients experienced 2 or fewer emetic episodes during TBI. For hemi-body irradiation, ondansetron (8 mg) and dexamethasone (8 mg) given orally produced complete control of emesis in 12 out of 14 patients. The effectiveness of this regimen now enables patients receiving hemi-body irradiation to be treated as outpatients in many cases. Anecdotal data also shows that ondansetron is effective when given as intervention treatment in patients with established emesis. In none of the studies were there any serious adverse events following ondansetron treatment. It can therefore be concluded that ondansetron is an effective and well tolerated antiemetic for the prophylaxis and treatment of radiation-induced emesis and nausea. The use of effective anti-emetic treatments may have resource implications such as reducing bed occupancy and enabling the use of fewer, larger fractions of radiotherapy. PMID- 8459989 TI - Improved control of emesis and quality of life with ondansetron in breast cancer. AB - Cyclophosphamide-based chemotherapy is often given to patients for the treatment of breast cancer. This chemotherapy can induce severe nausea and vomiting in these patients, which can adversely affect their quality of life, especially as these regimens are often given on an outpatient basis over several courses. This paper reviews 5 randomised, double-blind, multicenter comparative studies which have been carried out in breast cancer patients to evaluate the efficacy and safety profile of the potent and highly selective 5-HT3 receptor antagonist, ondansetron. These studies have shown that ondansetron is superior to placebo in the control of emesis induced by a 14-day CMF schedule and that it is superior to conventional anti-emetics (metoclopramide and alizapride) in the control of acute and delayed emesis induced by regimens containing high-dose cyclophosphamide. Ondansetron was well tolerated in these studies and did not induced any extrapyramidal reactions. The efficacy and tolerability of ondansetron was reflected in a better quality of life for patients given this anti-emetic which was formally assessed in 2 of the studies using the Rotterdam Symptom Checklist or the Functional Living Index-Emesis. In conclusion, ondansetron is an effective and well-tolerated anti-emetic for patients receiving cyclophosphamide-based chemotherapy for the treatment of breast cancer. Ondansetron provides significant benefits for patients' quality of life compared with conventional anti-emetics particularly as these patients are often treated on an outpatient basis and can be treated with oral ondansetron at home. PMID- 8459990 TI - Ondansetron: a cost-effective advance in anti-emetic therapy. AB - A cost-effectiveness analysis is one form of full economic evaluation where drug acquisition costs and the costs that are incurred as a result of using a particular treatment are assessed together with clinical efficacy. This paper reviews two such studies. One of the studies was a prospective randomised cost effectiveness study which compared ondansetron (8 mg i.v. 0, 4 and 8 h following chemotherapy) with metoclopramide (3 mg/kg i.v. followed by an infusion of 0.5 mg/kg/h for 8 h) over the first 24 h following chemotherapy in hospitalised patients receiving highly emetogenic chemotherapy. This study showed that the cost per successfully treated patient (defined in this study as having < or = 1 emetic episode and no adverse events) for these 2 treatments were approximately equal: ondansetron pounds 95 and metoclopramide pounds 92. The second study was an economic evaluation based on data collected over a 5-day period following cyclophosphamide-based chemotherapy given on an outpatient basis for the treatment of breast cancer. Patients received an intravenous dose of 16 mg dexamethasone with either 8 mg ondansetron or 60 mg metoclopramide intravenously before chemotherapy followed by oral dosing with 8 mg ondansetron or 20 mg metoclopramide 3 times daily for 5 days. The costs per successfully treated patient (defined in this study as no vomiting or retching episodes and no anti emetic-related adverse events during the 5-day period) were comparable: ondansetron pounds 184 and metoclopramide pounds 160. A recent study has established that ondansetron (8 mg) given orally twice daily is as effective as the same dose given 3 times a day. A sensitivity analysis using the cost of an ondansetron twice daily regimen showed that ondansetron is more cost-effective than metoclopramide (pounds 133 vs. pounds 160). These cost effectiveness studies have shown that ondansetron is at least as cost-effective as metoclopramide and simplified ondansetron dosing schedules render ondansetron more cost-effective. These full economic evaluations illustrate that drug acquisition costs can be a misleading guide to the economic impact of antiemetics. PMID- 8459991 TI - Global experience with ondansetron and future potential. AB - Ondansetron was first synthesised in 1983 and it is estimated that over 4 million patient treatments have been given with ondansetron in clinical practice. Clinical trials in over 15,000 patients have demonstrated that ondansetron is effective and well tolerated in a range of clinical settings, including adults and children and over repeated courses of treatment. Ondansetron is convenient to administer, being effective as a single intravenous dose for the control of acute emesis and as oral therapy on a twice-daily schedule. Recent studies have also shown it to be a cost-effective anti-emetic when the costs of treatment failure of traditional anti-emetics are taken into account. Studies have also demonstrated an improved quality of life with ondansetron compared to treatment with metoclopramide. Ondansetron has also been found to be effective in the prevention or treatment of postoperative nausea and vomiting and other studies are underway to investigate its potential use in other clinical settings. Furthermore, appropriately designed trials are ongoing to evaluate the place of ondansetron in the control of cisplatin-induced delayed emesis. In conclusion, ondansetron has been shown to be a major advance in the control of nausea and vomiting associated with chemotherapy and radiotherapy. PMID- 8459992 TI - A placebo for mitomycin C. PMID- 8459993 TI - An intractable problem. PMID- 8459994 TI - Surface toxicity of timolol. PMID- 8459996 TI - Optic nerve sheath decompression may improve blood flow in anterior ischemic optic neuropathy. AB - PURPOSE: The purposes of this study are to evaluate the retrobulbar circulation in progressive nonarteritic ischemic optic neuropathy (NAION) and to assess changes in blood flow after optic nerve sheath decompression (ONSD). METHODS: Twenty-five patients with progressive NAION were studied using color Doppler imaging (CDI) before and after ONSD. Blood flow velocities and vascular resistance were calculated for the ophthalmic artery, central retinal artery, and posterior ciliary arteries in each eye. Contralateral eyes served as the control group. RESULTS: Preoperatively, the study group demonstrated significantly lower blood flow velocities in the central retinal artery (P < 0.002) and posterior ciliary arteries (P < 0.02) when compared with the contralateral control group. Postoperatively, there was a significant increase in blood flow velocity in the ophthalmic artery (P < 0.04) and the central retinal artery (P < 0.05) as well as a significant decrease in vascular resistance in the posterior ciliary arteries (P < 0.02) in the study group. There were no significant changes in blood flow velocity or vascular resistance in the contralateral control group. Long-term follow-up on eight patients suggests a persistence of this trend. Seventeen of the 25 operated eyes demonstrated a postoperative improvement in visual function, defined as a gain of two lines or more in Snellen visual acuity or at least 20 degrees of visual field expansion. CONCLUSIONS: These data demonstrate that eyes with acute NAION have impaired blood flow when compared with the contralateral control group. Furthermore, they suggest that ONSD may improve blood flow to the ischemic optic nerve halting the progression of visual loss and in some cases improving visual function. PMID- 8459995 TI - Serving the public's interest--the National Eye Institute celebrates 25 years. PMID- 8459997 TI - Progressive and static nonarteritic ischemic optic neuropathy treated by optic nerve sheath decompression. AB - PURPOSE: Optic nerve sheath fenestration has been advocated as an effective treatment for progressive nonarteritic ischemic optic neuropathy (NAION) and anecdotally effective for selected patients with NAION who have not had progressive visual loss. To determine whether optic nerve sheath decompression is of any benefit in patients with NAION, the authors reviewed their experience, surgically treating 23 patients with progressive NAION and 15 patients with static or nonprogressive NAION. RESULTS: Patients with progressive NAION had a significant improvement in visual function as measured by Snellen visual acuity after optic nerve sheath decompression (P = 0.0005). There was no statistically significant improvement in visual field mean deviation (P = 0.11). The 15 patients undergoing optic nerve sheath decompression for static NAION failed to demonstrate significant improvement in either visual acuity (P = 0.90) or visual field mean deviation (P = 0.87). Preoperative standardized echography was used to measure the optic nerve sheath diameter and ascertain its compressibility (30 degrees test). There was a significant difference in compressibility between eyes with static NAION and eyes with progressive NAION (P = 0.001). Accumulation of optic nerve sheath fluid was documented in three eyes initially presenting with NAION and then with development of progressive visual dysfunction. CONCLUSION: Optic nerve sheath decompression improves visual acuity but has little effect on overall visual function in patients with progressive NAION. Optic nerve sheath decompression does not improve visual field or acuity in patients with static NAION. Detection of significant intrasheath fluid by standardized echography helps to objectively differentiate patients with NAION who may benefit from optic nerve sheath decompression. PMID- 8459998 TI - Color Doppler velocimetry of the optic nerve head in arterial occlusion. AB - BACKGROUND: Color Doppler velocimetry allows simultaneous imaging by B-scan and Doppler ultrasound. This facilitates estimation of blood velocity in the orbital vessels. A pulse arterial waveform providing blood velocity measurements can be obtained from the optic nerve head. The vascular pattern in this region consists of multiple peripapillary blood vessels and a central artery. The exact contribution of the arteries in this area to velocimetry readings was undetermined. METHODS: In this study, the arterial pulses at the optic nerve head of seven patients with central retinal artery occlusion (CRAO) and seven with anterior ischemic optic neuropathy (AION) were examined by color Doppler velocimetry. RESULTS: No velocimetric measurements were obtainable at the optic nerve head in three of four patients with acute CRAO (examined within 24 hours of onset) despite color recordings obtainable in the peripapillary region. In contrast, all patients with AION showed characteristic arterial pulse waveforms from the artery that was situated centrally in the optic nerve. No peripapillary color indices were detectable in three of the four patients with ischemic optic neuropathy who were examined within 24 hours of onset of their symptoms. Follow up investigation showed that there was reperfusion of both arterial circulations within 1 week. CONCLUSION: The results demonstrate that color Doppler ultrasound of the optic nerve head provides velocimetric measurements of blood flow in the central retinal artery. Although some investigators using different apparatuses have produced velocimetry measurements from the posterior ciliary arteries, in this study reliable measurements were not obtainable form color indices in the peripapillary area. PMID- 8459999 TI - Botulinum alignment for congenital esotropia. AB - BACKGROUND: Botulinum toxin injection into the medial rectus has been recommended by several investigators as an alternative to incisional surgery for treatment of patients with congenital (essential infantile) esotropia. Currently, there are no published studies demonstrating both the motor and sensory results of congenital esotropic patients aligned by botulinum toxin. METHODS: The author traveled to two medical centers to personally and objectively examine, with standardized testing methods, 12 patients with congenital esotropia who had been aligned for a minimum of 6 months by the age of 2 years by other investigators. The selected patients had been followed for a minimum of 3 years and were of sufficient maturity to reliably respond to sensory testing. A comparison was made between the author's conclusions about the binocularity results of these patients and the assessment of the treating ophthalmologists. RESULTS: Only 6 of the 12 patients demonstrated optimum motor alignment to within 10 prism diopters (PD) of orthophoria at the time of the study. A minimum of 1-month (average, 5 months) post-botulinum injection was found to be necessary to establish this alignment. Only three of these six aligned patients could both fuse and demonstrate gross stereopsis without the assistance of compensatory prisms. These results can be contrasted to a previously reported group of surgically aligned cases in which 66 of 90 patients aligned by 2 years of age could both fuse and demonstrate stereopsis, without any use of compensatory prisms. CONCLUSION: These results must be considered preliminary. However, alignment by botulinum appears to be less effective in establishing evidence for binocularity than incisional surgery in the treatment of congenital esotropia (P < 0.001). PMID- 8460000 TI - The sensitive period for strabismic amblyopia in humans. AB - PURPOSE: In order to assess the sensitive period for strabismic amblyopia, the period of susceptibility to monocular occlusion was investigated in 407 children who ranged in age from 21 months to 12 years. METHODS: Patients were treated between 1975 and 1990 by occlusion of the best eye. The efficiency of the treatment was measured as the ratio of reduction of the amblyopia at the end of the occlusion. RESULTS: The efficiency of the occlusion is shown to depend on the age of the onset of the treatment: recovery of acuity of the amblyopic eye was maximum when the occlusion was initiated before 3 years of age, decreased as a function of age and was about null by the time the patient was 12 years of age. CONCLUSION: This is assumed to be an indication of the sensitive period for strabismic amblyopia in humans. The results are discussed on the basis of the neurophysiological mechanisms of amblyopia established in animals. PMID- 8460001 TI - Centurion syndrome. Idiopathic anterior displacement of the medial canthus. AB - PURPOSE: To describe a series of patients with epiphora due to a medial canthal anomaly. This anomaly consists of an anterior displacement of the anterior limb of the medial canthal tendon and a prominent nasal bridge, with lid malposition away from the globe and displacement of the lacrimal puncta out of the tear lake. The authors use the term Centurion syndrome to describe this anomaly. METHODS: The history, results of examination, investigations, and surgical management and outcome of 13 patients with Centurion syndrome were reviewed. Seven patients were recalled for examination to complete patient details. RESULTS: All patients had epiphora since childhood, which worsened at puberty, and all were patent to syringing. Lacrimal scintillography (ten cases) showed a functional block at the inner canthus, with hold up of activity before entry into the sac. Surgery to restore lid globe apposition medially by release of the anterior limb of the medial canthal tendon (eight patients), sometimes combined with dacryocystorhinostomy (four patients), relieved the epiphora. CONCLUSION: There is a group of patients with unexplained epiphora due to a medial canthal anomaly, which the authors have termed Centurion syndrome. It is important to recognize this anomaly, as it can be corrected surgically by medial canthal tendon release or by medial canthal tendon release combined with dacryocystorhinostomy if there is concomitant lacrimal outflow obstruction. PMID- 8460002 TI - Ophthalmologic examination in the diagnosis of Proteus syndrome. AB - PURPOSE: To describe the clinical features of Proteus syndrome, a rare recently recognized hamartoneoplastic malformation, with emphasis on the ocular findings. METHODS: Complete physical and ocular examination of two new patients with Proteus syndrome. RESULTS: The two reported cases illustrate the wide clinical polymorphism of Proteus syndrome and the overlap of its clinical manifestations with those of other overgrowth syndromes. Both patients had periorbital exostoses and epibulbar tumors. The ocular findings are compared with those in the literature. CONCLUSION: Considering the paucity of information in the ophthalmic literature, this article explores the role of the ophthalmologist in diagnosing this rare entity. PMID- 8460003 TI - The conjunctiva in acute and chronic mucous membrane pemphigoid. An immunohistochemical analysis. AB - BACKGROUND: The mechanism of chronic progressive conjunctival cicatrization in mucous membrane pemphigoid is not well understood, and current therapy is often of limited use. Rapid progression of cicatrization follows exacerbations of clinical inflammation, and the investigation of immune mechanisms related to disease activity may provide a clue for more effective therapeutic strategies. METHODS: The authors undertook an immunohistochemical study, using monoclonal and polyclonal antibodies in glycol methacrylate-embedded tissues, of epibulbar conjunctival biopsy specimens obtained from 20 patients with ocular cicatricial pemphigoid and from 12 matched healthy controls. The study patients were classified according to the ocular disease activity as acute ulcerative (n = 4), subacute (n = 8), and chronic (n = 8). RESULTS: The composition of the subepithelial cellular infiltrate varied with disease activity. Acute disease was characterized by an abundance of macrophages and neutrophils. The number of T lymphocytes was significantly raised in all the disease groups, but were most marked in subacute disease. Of the T-cell subsets, there were more CD8- than CD4 positive cells observed, except in acute disease where there were equal numbers. Only approximately 5% of the T cells in all disease groups were activated as demonstrated by expression of interleukin-2 receptor. There was increased expression of major histocompatibility complex class II (MHC II) molecules on macrophages, fibroblasts, and other cells in all the groups. The number of B cells and natural killer cells was not increased. Staining for the fibrogenic cytokines, transforming growth factor-beta (TGF-beta), platelet-derived growth factor, and basic fibroblast growth factor was found in both pemphigoid patients and control persons, but the intensity of TGF-beta staining was significantly greater in acute disease. CONCLUSIONS: The composition of the cellular infiltrate in the bulbar conjunctiva depends on clinical disease activity. The numbers of neutrophils and macrophages seem to reflect clinical disease activity. Fibrogenic cytokines, especially TGF-beta, may play an important role in the formation of conjunctival scar tissue. PMID- 8460004 TI - Ocular evaporation in meibomian gland dysfunction and dry eye. AB - BACKGROUND: Secretions from the meibomian gland are believed to be important in reducing ocular surface water evaporation and preventing dry eye. Patients with blepharitis frequently have meibomian gland dysfunction with loss of meibomian glands (drop out). The authors hypothesized that dry eye that often occurs in patients with chronic blepharitis is secondary to increased evaporation associated with gland loss. METHODS: The authors measured the ocular surface water evaporation and tear osmolarity of patients with meibomian gland drop out and patients with gland drop out with a low Schirmer test. These findings were compared with those of a control group. RESULTS: The authors found that eyes with meibomian gland drop out and those with drop out and a low Schirmer test had a significantly higher evaporative rate at 30% relative humidity (average, 49.9 +/- 21 x 10(-7) g/cm2/second, or 0.49 +/- 0.29 microliters/minute evaporative loss per eye, and 59.1 +/- 28 x 10(-7) g/cm2/second, or 0.58 +/- 0.23 microliters/minute, respectively) when compared with those in the control group (average, 14.8 +/- 6 x 10(-7) g/cm2/second, or 0.15 +/- 0.07 microliters/minute [P < 0.05]). There was a significant correlation between evaporative rate and gland drop out (r = 0.522). CONCLUSION: Patients with meibomian gland drop out, and especially those with low tear production by Schirmer test, have an increased risk of dry eye developing through increased evaporation. PMID- 8460005 TI - Generalized transluminance of the iris and the frequency of the pseudoexfoliation syndrome in the eyes of transient ischemic attack patients. AB - BACKGROUND: Abnormal generalized iris transluminance has been reported to have connection with the pseudoexfoliation syndrome (PXS). According to angiographic studies, microvascular changes are found to be present on the iris of these patients, which suggests that hypoxia has a role in the development of PXS. On the other hand, carotid transient ischemic attack (TIA) patients have been shown to have some ocular key symptoms due to hypoxia. METHODS: Iris photographs of 62 unselected TIA patients (124 eyes) and 32 healthy subjects (64 eyes) were evaluated in a blind trial to show the presence of iris transluminance of these eyes. Biomicroscopic examination was performed to show the presence of the PXS. RESULTS: Abnormal iris transluminance was positive in 42% of the right eyes and in 45% of the left eyes in patients in the study group. The corresponding figures for the control group were 16% in both eyes (P = 0.01, chi-square test). When the study group was divided into subgroups according to stenosis of carotid bifurcation, the figures were highest in those cases where one or both carotid arteries were stenosed over 50%. Pseudoexfoliation syndrome was found in 18% of the right eyes and in 23% of the left eyes of TIA patients. The frequency of PXS in these eyes was approximately two times higher than reported in earlier studies of the frequency of PXS in healthy subjects of the same age in a Finnish population. CONCLUSION: Abnormal iris transluminance is one of the ocular key symptoms of extracranial cerebrovascular disease. Coexistence of cerebrovascular disease with abnormal iris transluminance, together with increased prevalence of pseudoexfoliation supports the theory that hypoperfusion is a contributory factor in the development of PXS. PMID- 8460006 TI - Subconjunctival THC:YAG ("holmium") laser thermal sclerostomy ab externo. A one year report. AB - BACKGROUND: Laser sclerostomy can be performed in a less-invasive manner than standard filtering surgery. Longer wavelengths in the infrared range have water absorptive characteristics that facilitate perforation of the sclera. The goal was to perform laser sclerostomy ab externo to avoid intraocular instrumentation and minimize conjunctival trauma. METHODS: A thulium, holmium, chromium-doped:YAG (THC:YAG) crystal laser was used to create thermal sclerostomies in 49 glaucomatous eyes of 46 patients. The laser is a long-pulsed (300-microsecond), compact, self-contained, solid-state laser operating in the near infrared (2.1 microns). Energy was delivered via a specially designed 22-gauge (712-microns) optic probe that emits energy at a right angle to the long axis of the fiber. Pulse energies of 80 to 120 mJ were used. Total energy levels to produce full thickness sclerostomies ranged from 1.4 to 7.2 J. Subconjunctival 5-fluorouracil (5-FU) injections were administered in 46 eyes. Success was defined as an intraocular pressure (IOP) of less than or equal to 22 mmHg with or without medications. For eyes in which preoperative IOP was less than or equal to 22 mmHg, success was defined as a decrease in IOP of greater than or equal to 30%. RESULTS: Estimated probability of success allowing for one retreatment was 0.75 at 6 months and 0.68 at 12 months. Mean IOP of successful cases was 13.3 mmHg at both 6 and 12 months. Twelve cases failed within the initial 6 months, and two additional cases failed by 12 months. CONCLUSION: THC:YAG ("holmium") laser thermal sclerostomy is an alternative to other full-thickness filtration procedures. Further evaluation and understanding will define its ultimate role in glaucoma management. PMID- 8460007 TI - Effects of intraoperative 5-fluorouracil or mitomycin C on glaucoma filtration surgery in the rabbit. AB - PURPOSE: To establish the effects of single intraoperative exposures to either 5 fluorouracil (5-FU) or two different concentrations of mitomycin C (MMC) on filtration surgery in the rabbit. METHODS: A prospective, randomized, masked observer, placebo-controlled study was performed to compare the effects on filtration surgery in rabbits of a single 5-minute intraoperative exposure to 5 FU (50 mg/ml), MMC (0.2 mg/ml), or MMC (0.4 mg/ml) with control eyes treated with distilled water. RESULTS: Intraocular pressures (IOPs) remained lower for longer and bleb survival was increased (P < 0.05) with all three treatments compared with control eyes. The effect of 5-FU was more transient than MMC. Bleb survival was prolonged in the following order: MMC 0.4 > MMC 0.2 > 5-FU 50 mg/ml. At 30 days, blebs were present in 100% of eyes treated with MMC 0.4 mg/ml, 60% of eyes treated with MMC 0.2 mg/ml, and 0% of eyes treated with 5-FU 50 mg/ml or distilled water. The blebs in the eyes treated with MMC were thinner, and significant complications (endophthalmitis, transient corneal opacification and neovascularization, and a presumed bleb leak) only occurred in the eyes treated with MMC 0.4 mg/ml. CONCLUSIONS: The authors' results suggest that 5-FU and MMC at these concentrations, delivered as a single intraoperative dose, prolong the survival of filtration surgery for different lengths of time in the rabbit, which is a model that normally exhibits aggressive healing and rapid failure of filtration surgery. The implications of these potentially titratable effects for filtration surgery in different categories of patients are discussed. PMID- 8460008 TI - Intraocular tissue plasminogen activator concentrations after subconjunctival delivery. AB - BACKGROUND: Topical application of recombinant tissue plasminogen activator (tPA) results in detectable intraocular tPA levels. The authors sought to determine whether subconjunctival delivery of recombinant tPA results in enhanced intraocular drug levels. METHODS: One week after first performing a gas vitrectomy in each eye, the authors injected 0.4 ml of a tPA solution (1 or 10 mg/ml) subconjunctivally in one eye of 16 rabbits and 0.4 ml of sterile water in the fellow control eye. Vitreous taps were performed to obtain vitreous samples for measuring tPA concentrations. An anterior chamber paracentesis was then done for each concentration at 15, 30, and 60 minutes. Aqueous and vitreous tPA concentrations were determined using a two-site enzyme-linked immunosorbent assay (ELISA). RESULTS: Vitreous tPA levels were higher than aqueous levels in the treated eyes. Vitreous levels averaged 7 +/- 7 ng/ml for the 1-mg/ml group (n = 7/7) and 202 +/- 230 ng/ml for the 10-mg/ml group (n = 7/8). Aqueous levels were positive in 8 of 16 samples. The authors conclude that subconjunctival delivery of tPA results in both vitreous and aqueous tPA levels. PMID- 8460009 TI - Calcific phacolysis. AB - BACKGROUND AND METHODS: The authors report the clinical and ocular histopathologic findings in three patients with longstanding unilateral post traumatic blindness. After one or more decades, acute pain associated with conjunctival hyperemia and apparent keratoprecipitates or a hypopyon developed in the affected eye of each individual. Phacoanaphylaxis was diagnosed preoperatively in two patients. RESULTS: Calcified granular lens fragments were dispersed throughout all three eyes. The anterior chamber in all patients contained extracellular calcified lens particles, but only one eye contained conspicuous macrophages. Two eyes showed elevated intraocular pressure (IOP), and in one patient calcified particles extended into a glaucomatous optic nerve head. CONCLUSION: To the authors' knowledge, this is the first report describing a rare condition involving the intraocular dispersal of calcified lens particles after disruption of the lens capsule. The authors have designated this entity as calcific phacolysis. PMID- 8460010 TI - Intraocular lens exchange for anterior chamber intraocular lens-induced corneal endothelial damage. AB - BACKGROUND: Anterior chamber and iris-plane intraocular lenses (IOLs) have been implicated in causing corneal endothelial damage and progression to pseudophakic bullous keratopathy. METHODS: The authors performed IOL exchanges on 102 eyes with signs of early corneal decompensation or progressive endothelial cell loss associated with these anterior chamber or iris-plane IOLs. Replacement IOLs were posterior chamber lenses sutured to the iris (87 eyes), sutured to the sclera (3 eyes), or placed in the ciliary sulcus (12 eyes). RESULTS: Seventy-two eyes (71%) had the same or improved vision after a mean follow-up period of 18.6 months (range, 6 to 60 months). Only 24 eyes (23.5%) progressed to corneal decompensation. Of the eyes that decompensated, 75% had preoperative endothelial cell counts of 500 cells/mm2 or less (P < 0.0001), and 83% had preoperative signs of early corneal decompensation (P < 0.001). Biomicroscopic signs of early corneal decompensation seen preoperatively in 50 eyes resolved in 17 eyes (34%) and remained unchanged in 12 eyes (24%) at the last postoperative follow-up visit. CONCLUSION: Removal of anterior chamber and iris-plane intraocular lenses in eyes showing signs of endothelial damage may prevent progression to pseudophakic bullous keratopathy if performed before a critical degree of endothelial cell loss or dysfunction has developed. PMID- 8460011 TI - Extracapsular cataract extraction in proliferative diabetic retinopathy. AB - PURPOSE: To establish the visual prognosis, prevalence of complications, and optimal strategy for management of proliferative diabetic retinopathy (PDR) in isolated extracapsular cataract extraction (ECCE). METHOD: This is a retrospective review of 56 patients with PDR who underwent ECCE with lens implantation. Results were compared with 64 patients with background diabetic retinopathy (BDR) operated on during the same time period. RESULTS: Final visual acuity (67% > or = 20/40) was better in BDR eyes compared with PDR eyes (21% > or = 20/40; P < 0.001). In eyes without maculopathy, 94% with BDR achieved a final visual acuity of at least 20/40 compared with 52% with quiescent proliferative retinopathy (P < 0.001). Final visual acuity in eyes with maculopathy was better in BDR eyes (36% > or = 20/40) than in PDR eyes (5% > or = 20/40) (P < 0.02). No patient with active proliferative or preproliferative retinopathy achieved a final visual acuity of more than 20/80. Postoperative deterioration of retinopathy occurred in 50% of patients with active proliferative retinopathy compared with 10% with quiescent proliferative retinopathy (P < 0.01) and 3% with BDR (P < 0.001). Immediate postoperative fibrinous anterior uveitis, which prevented early panretinal photocoagulation, developed in over half the patients with active proliferative retinopathy. CONCLUSIONS: Final visual acuity after cataract extraction in diabetic patients with proliferative retinopathy is generally poor; however, in patients with quiescent proliferative retinopathy and no maculopathy, visual acuity may be good. Active proliferative retinopathy at the time of surgery is a poor prognostic indicator for final visual acuity and is associated with postoperative deterioration of retinopathy and fibrinous uveitis, which may preclude immediate postoperative panretinal photocoagulation. PMID- 8460012 TI - Histopathologic findings in congenital grouped pigmentation of the retina. AB - BACKGROUND: Congenital grouped pigmentation of the retina is a condition characterized by multiple, well-circumscribed, flat, pigmented fundus lesions clustered in a fashion resembling "bear tracks." METHODS: Light and electron microscopy was used to study these lesions in an eye of a 2-year-old boy. The eye was enucleated for retinoblastoma. RESULTS: Similar to the classic, solitary, congenital hypertrophy of the retinal pigment epithelium (CHRPE), the involved RPE cells contained an increased number of large pigment granules. Unlike CHRPE, most pigment granules retained the normal ellipsoidal shape. In addition, hypertrophy and hyperplasia of the RPE cells were not significant features by light and electron microscopy. CONCLUSION: Although the lesions in this case superficially resembled CHRPE by light microscopy, ultrastructural differences were identified. PMID- 8460013 TI - The relationship of cardiovascular disease and its risk factors to age-related maculopathy. The Beaver Dam Eye Study. AB - PURPOSE: To examine the association between cardiovascular disease and its risk factors to age-related maculopathy in a population-based study of people between the ages of 43 and 86 years (n = 4926) between 1988 and 1990. METHODS: Population based prevalence study using standardized protocols for physical examination, blood collection, administration of a questionnaire, and stereoscopic color fundus photography to determine age-related maculopathy. Standard univariate and multivariate analyses were performed. RESULTS: After controlling for age, early age-related maculopathy was related to low total serum cholesterol levels in women and a high high-density lipoprotein (HDL) cholesterol level and a low total cholesterol/HDL-cholesterol ratio in men. After controlling for age and sex, age related exudative macular degeneration was associated with higher hematocrit values (odds ratio, 1.09; 95% confidence interval, 1.00, 1.19) and higher leukocyte count (odds ratio, 1.10; 95% confidence interval, 1.00, 1.19). There was no statistically significant relationship between blood pressure, hypertension, or history of cardiovascular disease and exudative macular degeneration or geographic atrophy. CONCLUSION: With the exception of relationships between serum lipids and early age-related maculopathy, and hematocrit values, leukocyte counts, and exudative macular degeneration, these data suggest that most cardiovascular disease risk factors are not related to age related maculopathy. Further longitudinal study is needed. PMID- 8460014 TI - Arteriovenous crossing patterns in branch retinal vein occlusion. The Eye Disease Case-Control Study Group. AB - PURPOSE: The study was designed to evaluate the relative anatomic position of the crossing vessels at the site of occlusion in eyes with branch retinal vein occlusion (BRVO). METHODS: Fundus photographs of 106 eyes (104 patients) with recent BRVO from the Eye Disease Case-Control Study were used to examine the relative position of artery and vein at occluded crossings. Three separate comparison groups were formed by identifying corresponding arteriovenous crossings for each occluded crossing in: (1) the ipsilateral but opposite vessel arcade within eyes affected by BRVO; (2) the same quadrant in unaffected eyes of BRVO patients; and (3) the same quadrant in eyes of patients without BRVO, matched by age, sex, and race with the BRVO patients. RESULTS: The site of obstruction of the branch vein was an arteriovenous crossing in all affected eyes. In 99% of eyes with BRVO, the artery was located anterior to the vein at the obstructed site. In the three comparison groups, the artery was anterior to the vein in 62%, 61%, and 54% of the crossings, respectively, yielding statistically significant differences for each group of control crossings compared with BRVO crossings (P < 0.001). CONCLUSION: Finding the vein to be consistently between the more rigid artery and the retina at almost all arteriovenous crossings affected by BRVO suggests a possible role for mechanical obstruction in the pathogenesis of BRVO. PMID- 8460015 TI - Ophthalmology and vanity fair. AB - Vanity Fair was the leading Society magazine of Victorian and Edwardian England. A key feature of each weekly issue was the inclusion of a chromolithographed caricature and biographic sketch of a prominent individual. The author undertook a survey of the more than 2000 caricatures published from 1869 to 1914 to determine if any portrayed an ophthalmologist. Seventy-nine of the caricatures depicted physicians and scientists, of whom three were ophthalmologists: Sir Jonathan Hutchinson, Sir Robert Brudenell Carter, and Sir Anderson Critchett. A brief sketch of their ophthalmic accomplishments is presented. Caricatures from Vanity Fair are avidly sought after and are often found in antique shops, sporting venues, and professional offices, especially those of lawyers and judges. It has been said that when seeking the true perspective of the Victorian and Edwardian eras, the most faithful mirror and record of representative men and the spirit of their times can be found in Vanity Fair. PMID- 8460016 TI - [Mechanism of free radicals in gastrointestinal and liver diseases]. AB - Free radicals produced in biological systems may be important pathologic mediators in different tissue injuries, and the present paper is devoted to overview their role in gastrointestinal and liver diseases. After giving a brief answer to the basic question what are free radicals and lipid peroxidation, on the ground of experimental findings, the significance of the free radical mechanisms has been discussed in gastric ulcerogenesis, ischaemia/reperfusion induced intestinal injuries and inflammatory bowel diseases, in pancreatitis and alcoholic, toxic and metabolic origin liver damages. The better understanding of these tissue damaging mechanisms may provide a foundation for therapeutic breakthroughs in gastroenterology. PMID- 8460017 TI - [Serologic monitoring of patients with endometrial carcinoma using ovarian carcinoma antigen (CA 125)]. AB - The serum concentrations of CA 125 were determined in 136 corpus carcinoma patients. Before the primary irradiation therapy in 40.2% (19/47), after the hysterectomy 3.4% (3/89) of the patients had elevated (> 35 U/ml) CA 125 levels. CA 125 values above the normal range were frequently associated with advanced stages. Measuring elevated levels after hysterectomy proved bad prognosis. There were no correlation of CA 125 levels and degree of the histological type and differentiation of the tumor. Serological follow up revealed a correlation with the clinical course of the endometrial carcinoma in 62% (31/50). 18 cases who had tumor progression associated rising CA 125 levels. In 10 patients with tumor progression the CA 125 levels increased before clinical sign of progression with a median lead time of one month. The determination of CA 125 is recommended to check the endometrial carcinoma patients and to detect progression of the tumor. PMID- 8460018 TI - [Value of computer tomography in the diagnosis of lung hamartomas]. AB - Detailed radiological examinations were undertaken in six cases of hamartochondromas verified by histopathology on surgical samples. It has been shown that examination of lung hamartochondromas by computer tomography provides a good approach for separation of different tissues constructing hamartochondromas. Thus cartilage, lose and dense and mixed forms of connective tissue, and adipose tissue can be well separated. The growth rate of hamartochondromas is very slow, characterized by doubling times of several hundred to several thousand hours. PMID- 8460019 TI - [The role of free radical scavengers in gastrointestinal diseases]. AB - Be it ever so complex the natural antioxidant scavenger system of the organism, the protection provided by it seems to be inappropriate in certain diseases of the gastrointestinal mucus membrane, such as chronic inflammation, immune- and malignant diseases of the bowel. Despite the wide range of therapeutic attempts, the treatment of these diseases has not yet been solved, and the anti inflammatory-, immunomodulatory-, cytostatic drugs currently used, have several side effects. Therefore, the so called natural- and synthetic antioxidants have been more widely employed for additional and adjuvant treatment. It also has become clear that the direct free radical scavenging effect and/or the membrane protection play an important role in the action mechanism of several old established drugs. The recent report lists those natural and synthetic antioxidants which have been successfully employed in the clinical treatment of bowel diseases. Among the natural antioxidants, a protective effect of vitamins A, C and E have been demonstrated in the treatment of gastroduodenal ulcer and gastric cancer. Among the synthetic antioxidants, 5-amino-salicylic acid was the most effective drug in the treatment of chronic inflammations of the bowel. With getting the more precise knowledge about details of free radical reactions and with clearing up their role in pathological processes, it is possible to develop new and effective synthetic antioxidants, and widely employ them therapeutically. PMID- 8460021 TI - [Importance of clear terminology in the language of medicine]. PMID- 8460020 TI - ["Busulfan lung" simulating tumor]. AB - The authors present a case in which a patient, treated with Myleran for chronic myeloid leukaemia showed tumour like changes in the lung. They stress the differential diagnostic difficulties and the importance of histological diagnosis. This case proves that with discontinuation of the therapy the lung change may be reversible. PMID- 8460022 TI - ["Medicina 2000"]. PMID- 8460023 TI - [The new nursing legislation. A summary of the main contents of supplements to the nursing legislation decided on by parliament during the last year]. PMID- 8460024 TI - [Care of old and chronically ill patients--the road to holistic care. A committed appeal to all those engaged in geriatric nursing. A plea for changing instead of quitting which really ought to generate courage...]. PMID- 8460025 TI - [Communicating--an activity of daily living, also in retirement and nursing homes]. PMID- 8460026 TI - [The nursing staff's fear of the patient]. PMID- 8460028 TI - [Companion on the last passage. Who has been living for his lifetime with an animal has a right to be with it when he is severely or even terminally ill]. PMID- 8460027 TI - [Geriatric care--from theory to practice]. PMID- 8460029 TI - [The new education for the care of the well and the ill may start]. PMID- 8460030 TI - [Nursing models--a means for reorientation]. PMID- 8460031 TI - [The Roper, Logan and Tierney nursing model]. PMID- 8460032 TI - [Dorothea Orem--the model of self-care]. PMID- 8460033 TI - [Clothes make people--people make clothes]. PMID- 8460034 TI - [Mixed feelings ... reform in nursing education]. PMID- 8460035 TI - Common benign cutaneous tumors and tumor-like lesions of the head and neck. AB - The otolaryngologist is confronted with a wide variety of benign and malignant skin neoplasms. In this article, common benign cutaneous, epithelial, and nonepithelial tumors and tumor-like lesions of the head and neck region are described. Clinical presentation, histopathology, and differential diagnosis are discussed where appropriate. PMID- 8460036 TI - Nonsurgical management of primary skin malignancies. AB - Cryosurgery, electrosurgery, radiotherapy, chemotherapy, and interferon therapy achieve high cure rates for primary skin malignancies. These techniques are readily mastered. They combine cost-effective use of time, space, and equipment. Proper patient selection maximizes safety, comesis, and cure rates. PMID- 8460037 TI - Cutaneous micrographic surgery. AB - Cutaneous micrographic surgery (CMS) is a highly effective method of treating cutaneous malignancy. With high cure rates and conservative removal of normal tissue. CMS is the treatment of choice for cutaneous malignancies that are difficult to treat. Basal cell and squamous cell carcinomas that are large, recurrent, or in high-risk locations; that have unfavorable histologies; or that have been treated previously with other modalities should be considered for treatment with CMS. PMID- 8460038 TI - Immediate versus delayed repair of skin defects following resection of carcinoma. AB - Facial defects resulting from excision of skin malignancies may be reconstructed with flaps or grafts immediately or in delayed fashion, or the wound may be allowed to heal by secondary intention. The merits of each option are discussed along with a brief review of the pertinent details of wound healing. A small delay in reconstruction of up to 3 to 4 days can be tolerated safely with no compromise of results. When healing by secondary intention is chosen, fenestration speeds coverage of the wound, and moist dressings with antibiotic ointment effectively prevent infection and expedite epithelialization. PMID- 8460039 TI - Special considerations in the management of malignant skin lesions about the eye. AB - The periocular midface is a complex anatomic region in which the spread of cutaneous malignancies is determined not only by the tumor pathology but also by adjacent natural anatomic barriers. The resulting management considerations when treating malignancies in this region are discussed in this article. PMID- 8460040 TI - Special problems associated with cutaneous carcinoma of the ear. AB - Cancer of the ear is similar, in many respects, to cancer of other skin-covered parts of the body. The aggressive nature of malignancies involving the ear is often underestimated, resulting in initial undertreatment. Later, the price is paid when a much more extensive operation is required to exenterate the cancer. A more aggressive initial approach to surgical cure would often result in less morbidity and also less mortality. One should therefore be reasonably aggressive in the initial surgical management of all malignancies, including basal cell carcinoma. When cancer involves the meatus, one should be prepared to perform a lateral temporal bone resection to ensure complete tumor extirpation. The available reconstructive options, including hearing rehabilitation, allow aggressive treatment to be tolerated reasonably well by most patients. Aggressive surgical resections of the external ear can be reconstructed, with very reasonable cosmetic and functional results. With sufficiently aggressive treatment, the chances for successful tumor control can be generally very good. PMID- 8460041 TI - Special problems associated with carcinoma of the nose. AB - Because of its prominent location on the face, the nose is the primary target for sun-induced skin cancers. The unique anatomical features of the nose account for the unusually high rate of recurrence of tumors at this site. The reasons are multifactorial and have been discussed. Special care must be undertaken in managing cutaneous neoplasms arising in this region, for failure to control disease can lead to catastrophic events and eventually to the demise of the patient. Likewise, tumor recurrence and multiple therapeutic endeavors are associated with progressive facial deformity that impacts significantly on the patient's self-image and ability to interact socially. Reconstruction of nasal defects must be predicated on complete tumor ablation and documented by histologic evidence. Patients with high-risk lesions or in whom tumor margins are in question should undergo a period of observation before definitive reconstruction is contemplated. Although multiple reconstructive options are available, decisions relating to timing, advisability, and appropriate technique must be individualized. These judgments are based on the experience and bias of the surgeon as well as the goals and concerns of the patient. PMID- 8460042 TI - Carcinoma of the lip. AB - Lip carcinoma is a relatively unique malignant disease because the lip is a junctional structure. It accounts for 12% of all noncutaneous head and neck cancers, yet has the lowest disease-related mortality rate among this group of cancers. The lip is bounded externally by the facial skin and is continuous with the buccal mucosa in the oral cavity. These adjacent sites are often involved by the larger lip carcinomas, just as the lip may be involved by skin or buccal mucosal carcinomas. The lymphatic drainage of both the upper and lower lips is primarily to the submandibular group of lymph nodes. To a lesser extent, drainage may go to submental intraparotid, or internal jugular lymph nodes. Contralateral lymph node drainage is possible. Lip carcinoma is almost exclusively squamous cell carcinoma, the major etiologic factor being prolonged solar exposure. The lower lip is the affected site in more than 90% of cases. Deviant growth patterns, histologic grade, perineural invasion, and thickness have all been found to correlate with patient outcome for this tumor. Treatment for lip carcinoma is usually surgical, in the form of full-thickness excision with margins of 8 to 10 mm. Adjacent nonlip structures that are contiguously involved by the malignant process must be included in the resection. Neck dissection is also performed when clinically palpable lymph nodes are present. For lip cancers smaller than 2 cm, cure rates of greater than 90% may be expected. Extremely large lesions and those associated with lymph node metastases have expected cure rates of 50% or less. PMID- 8460043 TI - Malignant neoplasms of the scalp. Etiology, resection, and reconstruction. AB - Malignant scalp neoplasms initially spread by radial extension with deep invasion occurring relatively late in the course of disease. Basal cell carcinomas have the highest incidence followed by squamous cell carcinomas and melanomas. Surgical excision provides the best chance of cure in the majority of cases. Tumor histology influences decisions about margins of resection and regional lymph node dissection. Primary closure usually can be obtained for scalp defects measuring up to 3 cm in diameter. Larger defects can be reconstructed with skin grafts, local flaps, musculocutaneous flaps, free flaps, or transposition flaps following tissue expansion. PMID- 8460044 TI - Radiation therapy for skin tumors. AB - Radiation therapy is an acceptable alternative for the treatment of many malignancies of the skin. Results are gratifying, and long-term sequelae are few. In basal cell and squamous cell carcinomas, radiation is often the best treatment when surgery is expected to cause excessive morbidity or mortality or require extensive reconstruction. Radiation should be considered as first-line treatment for tumors in the midfacial triangle. It is also very acceptable treatment for Kaposi's sarcoma and mycosis fungoides. Radiation can be used for melanoma, although it is not standard first-line therapy. Radiation is probably the treatment of choice for Merkel cell carcinoma. PMID- 8460045 TI - Photodynamic therapy for cutaneous malignancies of the head and neck. AB - Photodynamic therapy is a modality that potentially could be most helpful in treating multicentric skin cancers. Although a number of reports are present in the literature relating to this treatment, the results are conflicting and confusing. This article summarizes the current literature and suggests future directions. PMID- 8460046 TI - Inducing pain in children--a controversial issue. PMID- 8460048 TI - Toward validation of pain measurement tools for children: a pilot study. AB - We undertook to explore the validity of pain measurement tools for use in children in the postoperative period. The general approach was to determine the extent to which a measurement tool conformed with the clinical expectations about pain in the postoperative period; namely, that pain is low prior to surgery, increases following surgery, decreases with pain medication and decreases over time following surgery. In children aged 6 months to 3 years, we evaluated the CHEOPS and Observer pain scales. In children 3-6 years of age, we used the CHEOPS, Observer and Faces scale. In children 6-12 years of age, we studied the CHEOPS, Faces and visual analogue scales. In all instances, each of the scales conformed with the clinical expectations about pain following surgery. In addition, these scales were correlated with each other. Within the limitations of the measurement techniques used, these data provide support for the validity of the measurement tools evaluated. PMID- 8460047 TI - Pain in the preterm neonate: behavioural and physiological indices. AB - The impact of invasive procedures on preterm neonates has received little systematic attention. We examined facial activity, body movements, and physiological measures in 56 preterm and full-term newborns in response to heel lancing, along with comparison preparatory and recovery intervals. The measures were recorded in special care and full-term nurseries during routine blood sampling. Data analyses indicated that in all measurement categories reactions of greatest magnitude were to the lancing procedure. Neonates with gestational ages as short as 25-27 weeks displayed physiological responsivity to the heel lance, but only in the heart rate measure did this vary with gestational age. Bodily activity was diminished in preterm neonates in general, relative to full-term newborns. Facial activity increased with the gestational age of the infant. Specificity of the response to the heel lance was greatest on the facial activity measure. Identification of pain requires attention to gestational age in the preterm neonate. PMID- 8460049 TI - Children of chronic pain patients: risk factors for maladjustment. AB - Recent research has documented negative effects of chronic pain problems on patients' spouses and children. This study examined the adjustment of children of 35 chronic pain patients, compared with children of 29 healthy controls, and the relationship of specific parental characteristics to child adjustment. Pain group children had significantly more teacher-rated behavior problems and significantly lower teacher-rated social competence than did control group children. Children of male patients were rated by parents as significantly less socially competent than children of female patients. Compared with controls, pain patients and their spouses reported significantly more depression, and pain patients were significantly more disabled. Patient functional disability was significantly associated with parent-rated child behavior problems, but group membership, patient gender, patient depression, and patient marital satisfaction were not. Child social competence was predicted by patient gender, but was not predicted by patient depression or disability, group membership, or by patient marital satisfaction. The results suggest that children of chronic pain patients may be at risk for adjustment problems. PMID- 8460050 TI - Low-dose amitriptyline as an adjunct to opioids for postoperative orthopedic pain: a placebo-controlled trial. AB - Tricyclic antidepressants (TCAs) have been found to be useful in the management of a variety of chronic pain conditions, although there is little published regarding the potential efficacy of this class of drug as an adjunct for the control of acute postoperative pain and related symptoms. Twenty-eight patients undergoing total hip or knee arthroplasty completed a randomized, placebo controlled, double-blinded trial of 50 mg of amitriptyline p.o. HS on postoperative days 1, 2 and 3 while using patient-controlled morphine or meperidine analgesia (PCA). Visual analog (VAS) and numerical verbal (NVS) pain ratings, sedation scores, sleep quantity/quality scores, and sense of well-being scores were assessed twice daily on each of the days succeeding amitriptyline/placebo use. Hourly opioid use was recorded and transcribed from the memory of the PCA devices in use. Mean scores in the amitriptyline group for pain NVS were greater (P < 0.05) (higher score = greater pain) on day 1 and greater on day 2 for the pain VAS. Mean scores for sense of well-being were greater (P < 0.05) (higher score = better sense of well-being) for the placebo group on days 1 and 2. On days 2 and 3, sleep scale variable mean scores were worse in the placebo group (P < 0.025). There were no other statistically significant differences between the control and active drug groups for any of the outcome variables measured. We conclude that amitriptyline at the dose prescribed is no different than placebo in altering the majority of postoperative symptom variables studied in the sample study population but caused no significant adverse effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8460051 TI - Polymedication and medication compliance in patients with chronic non-malignant pain. AB - Most reports of polymedication among patients with chronic non-malignant pain have relied only on the patient's statements which have been proven to be unreliable regarding actual drug consumption. This study investigates the incidence of polymedication and medication compliance in these patients by applying objective methods. One-hundred-nine consecutive patients predominantly with facial, neuropathic or back pain were interviewed about present medication at first admission to the pain clinic. Reports were verified by toxicological urine screening, mainly with thin-layer chromatography (TLC) and gas chromatography-mass spectrometry (GC-MS) coupling. Follow-up investigations of 61 patients were conducted within 1 and 24 months after beginning therapy. Polymedication--here defined as daily intake of 3 or more preparations--was found in 41 patients (38%) in the initial investigation. In only 74 patients (68%) did the results of urine screening correspond with their reports: 23 patients (21%) concealed the consumption of drugs, and 2 patients (2%) did not take their medications. Ten cases were not interpretable. Fifty-four percent of the drugs concealed were psychotropic substances, mostly benzodiazepines, and 42% were analgesic combinations, partly with psychotropic additives. Drug intake was concealed significantly more often with polypharmacy which was occurring more frequently in patients with headache or facial pain, longer duration of pain, young age, psychiatric diagnosis and history of substance abuse. Patients with initial non-compliance were more likely to conceal drug consumption in follow-up investigations as well (P = 0.05). Therefore, screening for medication compliance in patients with chronic non-malignant pain is recommended, especially in those with the abovementioned risk factors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8460052 TI - Effects of excitatory amino acid receptor antagonists on a capsaicin-evoked nociceptive reflex: a comparison with morphine, clonidine and baclofen. AB - The rat isolated spinal cord-tail preparation has been employed to examine the effects of several antinociceptive drugs and excitatory amino acid (EAA) receptor antagonists on nociceptive reflexes (recorded in ventral roots) stimulated by peripheral application of capsaicin (CAP). Non-nociceptive monosynaptic and polysynaptic dorsal root-evoked ventral root potentials (DR-VRPs) were also examined. Morphine (0.01-3 microM) and clonidine (0.03-1 microM) inhibited CAP stimulated activity, but not the non-nociceptive dorsal root-evoked monosynaptic reflex (MSR) or polysynaptic (PSR) activity. These effects were antagonized by naloxone and efaroxan, respectively. The AMPA/KA receptor antagonists CNQX (0.1 100 microM) and DNQX (0.1-30 microM) blocked nociceptive activity and were 4-fold selective for CAP-evoked potentials compared to the monosynaptic reflex. Kynurenate (1-300 microM), DL-AP-4 (3-300 microM), L-AP-4 (3-300 microM), and the GABAB receptor agonist baclofen (0.1-10 microM), inhibited all evoked potentials with relatively little selectivity between nociceptive and non-nociceptive responses. NMDA receptor antagonism by AP-5 (100 microM) reduced nociceptive and non-nociceptive potentials by a maximum of 30-33%. These data indicate that AMPA/KA receptor-mediated synapses are involved in acute spinal nociceptive transmission and suggest that AMPA/KA receptor subtypes could provide novel analgesic targets. PMID- 8460053 TI - Effects of capsaicin on KCl-induced blood flow and sensory nerve activity changes in the tooth pulp. AB - Potassium ion-containing solutions have been shown to initially excite then depress intradental nerve activity (INA) when applied into deep dentinal cavities. The INA reflects activity originating in intradental A fibers. Application of KCl to deep dentinal cavities also induces an increase in pulpal blood flow (PBF). Capsaicin is known to exert a highly selective desensitizing effect on polymodal C-fiber nerve endings. These C fibers are generally believed to release vasoactive substances in response to stimulation. In order to determine if KCl exerts its vascular effect via activation of capsaicin-sensitive nerve fibers, we examined blood flow and sensory nerve responses to KCl obtained before and after capsaicin desensitization. The A-fiber nerve activity was determined by using INA recording technique. Blood flow was measured simultaneously from the same tooth using laser Doppler flowmetry. Local application of 0.25 M KCl to a deep dentinal cavity induced a brief spike burst and an increase in PBF of 76.0 +/- 14.6% (n = 8). Repeated applications of 0.25 M KCl caused a consistent increase in the peak PBF amplitude (n = 8). Local application of 100 microM capsaicin to a deep dentinal cavity caused an increase in PBF of 116.8 +/- 26.3% (n = 8) lasting 12-18 min, but capsaicin application did not appear to evoke any INA response. The amplitude of PBF in response to capsaicin application declined during repeated applications. Following repeated applications of capsaicin the PBF response to KCl was significantly reduced (9.9 +/- 4.3%, n = 8).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8460054 TI - Alfentanil for extracorporeal shock wave lithotripsy. PMID- 8460055 TI - Comments on R.C. Marks, T. Houston and T. Thulbourne, PAIN, 49 (1992) 325-328. PMID- 8460056 TI - Pakistan coin pain scale. PMID- 8460057 TI - Comments on Altmaier et al., PAIN, 49 (1992) 329-335. PMID- 8460058 TI - The effects of bile acid feeding on the development of ileal bile acid transport. AB - Sodium-dependent bile acid uptake is developmentally regulated in the rat ileum. Transport activity is abruptly expressed on postnatal d 17, although the mechanisms controlling this expression are poorly understood. Changes in bile salt metabolism and hepatic transport result in a marked increase in bile flow before postnatal d 17, and thus this study examined the effects of bile salt feeding on the development of ileal bile acid transport. Twelve-d-old rat pups were gavage-fed saline, taurocholate, or mannitol on a daily basis for 3 d. Sodium-dependent bile acid transport was studied by rapid filtration using ileal brush-border membrane vesicles prepared from the various experimental groups. Taurocholate feeding resulted in precocious development of sodium-dependent bile acid transport and induction of sucrase activity. Mannitol feeding, used as a control for the effects of diarrhea-induced stress, resulted in similar sucrase activity, yet sodium-dependent bile acid transport was induced to only half the level observed in taurocholate-fed animals (3.2 +/- 1.6 versus 6.9 +/- 2.0 pmol/mg protein/45 s, p < 0.001). Serum corticosterone levels were similar in the mannitol- and taurocholate-fed animals (3.8 +/- 1.3 versus 4.6 +/- 1.8 micrograms/dL). Both feedings lead to histologic maturation of the ileum, with a more pronounced effect in the taurocholate-fed pups. Bile salt feeding induces precocious expression of ileal bile acid transport, apparently by both diarrhea induced stress and a bile salt-specific effect. PMID- 8460060 TI - Reduced free-radical-trapping capacity and altered plasma antioxidant status in cystic fibrosis. AB - Plasma antioxidant status and total radical-trapping antioxidant potential (TRAP) of children (n = 24) with cystic fibrosis (CF) were compared with those of children (n = 21) without the disease. Children with CF were found to have elevated plasma concentrations of ascorbic acid (94.6 +/- 58.2 mumol/L), with respect to normal children (65.6 +/- 18.8 mumol/L). Plasma uric acid (330.8 +/- 84 versus 198.0 +/- 31 mumol/L p < 0.01) and sulfhydryl group (518 +/- 43 versus 363 +/- 31 mumol/L p < 0.01) concentrations were also elevated in CF. Vitamin E levels (16.9 +/- 1.8 versus 18.4 +/- 1.3 mumol/L) were at the low end of the normal range. Despite an overall increased antioxidant array, CF patients had a reduced TRAP capacity (488 +/- 34 versus 580 +/- 79 mumol/L, p < 0.05). TRAP measurements in CF patients showed a strong negative correlation (r = 0.80, p < 0.001) with high ascorbic acid concentration, suggesting a prooxidant effect of ascorbic acid. Oral administration of ascorbic acid to adults was found to diminish TRAP activity. Concentrations of ascorbic acid similar to those seen in CF patients were attained in ascorbate-supplemented individuals, with substantial decreases in TRAP capacity. These studies suggest that high plasma ascorbic acid levels in children with CF may have a prooxidant effect. This appears to reduce the extracellular antioxidant defense of these children and may increase susceptibility to oxidative stress. PMID- 8460059 TI - Effect of the severity of maternal zinc deficiency on pregnancy outcome and infant zinc status in rhesus monkeys. AB - To investigate the effects of the severity of maternal zinc deficiency on early development, rhesus monkeys were fed diets that were either moderately zinc deficient (MZD) (2 micrograms Zn/g) or marginal in zinc (M) (4 micrograms Zn/g) throughout pregnancy and lactation. Dams in the MZD group developed overt signs of zinc deficiency. Compared with control dams fed diets adequate in zinc (C) (50 or 100 micrograms Zn/g), both M and MZD dams showed low mitogen response. Pregnancy outcome was similar in all groups, and infants were considered healthy at delivery. From birth until d 30, infants were closely monitored for signs of zinc deficiency. On d 30, infants were killed and tissues were analyzed for several parameters reported to be affected by zinc status. MZD infants tended to have lower plasma zinc concentrations than C infants, although the difference was only significant at d 14. M infants tended to have lower plasma zinc concentrations than C infants. Mitogen response was lower in MZD and M infants than in C infants. However, mitogen responses were similar in MZD and M infants. Liver zinc concentrations were similar among the three groups of infants; however, zinc and metallothionein concentrations in (10,000 x g) liver supernatant fractions were lower in the MZD and M groups than in the C group. 65Zn absorption/retention was higher in MZD and M mothers and infants than in C mothers and infants; there were no marked differences between MZD and M mothers or infants. In contrast to whole-body absorption, 65Zn uptake/retention by isolated hepatocytes was similar among the three infant groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8460061 TI - Single dose versus two doses of betamethasone for lung maturation in preterm rabbits. AB - Most previous studies of induced lung maturation have used fetal exposures to multiple doses of hormones, and such treatments are associated with fetal growth retardation in rodents and rabbits. This study was designed to evaluate whether single-dose maternal corticosteroid treatments could induce lung maturation without causing fetal growth retardation. Lung maturation was evaluated in 27-d gestational age rabbits by measurements of lung function after preterm delivery and ventilation. Lung function was assessed by measurements of ventilatory requirements, responses to exogenous surfactant, measurements of the recovery of intravascular albumin in the lungs, and surfactant pool sizes. As demonstrated previously, 0.1 mg/kg betamethasone (1 mg = 2.13 mumol betamethasone) given 48 and 24 h before delivery caused both growth retardation (birth weight 20% lower than controls, p < 0.01) and lung maturation (improved compliance, decreased radiolabeled albumin recoveries) despite lower alveolar saturated phosphatidylcholine pool sizes (p < 0.05 versus controls). A single dose of 0.2 mg/kg betamethasone given 48 h before delivery had an equivalent effect on birth weight as the divided doses of 0.1 mg/kg betamethasone, with the only lung maturational effect being a decrease in recovery of labeled albumin in alveolar washes (p < 0.01). A single dose of 0.1 mg/kg betamethasone given 48 h before delivery decreased birth weight by 9.4% (p < 0.01 versus control) but had no effect on any of the lung maturation indicators. Fetal lung maturation caused by maternal corticosteroid is associated with global fetal growth retardation, and a single low dose of corticosteroid can cause growth retardation without inducing lung maturation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8460062 TI - Effect of volume history on measurements of respiratory mechanics using the interrupter technique. AB - The importance of the viscoelastic properties of the tissues of the respiratory system has recently been recognized, and lung models have been produced to describe the resistive and viscoelastic properties of the lung. The pulmonary mechanics of 10 rabbits were studied using the interrupter technique to assess the effect of volume history on the resistive and viscoelastic elements of the respiratory system. The influence of the tone of the muscles of respiration was also studied. In healthy lungs, the resistive and viscoelastic elements of the lung are dependent on the volume history of the respiratory system and are significantly lower if these elements do not reach a resting position before expiration. The chest wall made a significant contribution to the resistive and viscoelastic elements of the respiratory system, which was also dependent on the lung volume history. The tone of the muscles of respiration had no effect on the resistive or viscoelastic elements of the respiratory system. PMID- 8460063 TI - Body fluid compartment volumes in chronically hypoxemic lambs. AB - Chronic hypoxemia is associated with a decreased growth rate and a decreased rate of cell division. In lambs with experimental cyanotic heart disease, the gain in body mass was decreased. In this study, we determined to what extent the lower body mass in these lambs was related to alterations in body fluid compartment volumes, specifically whether intracellular volume was decreased. Therefore, fluid compartment volumes were studied in nine lambs, after 3 to 4 wk of experimental cyanotic heart disease, and in 13 control lambs. Hypoxemic lambs had a lower arterial oxygen saturation (65 +/- 11 versus 91 +/- 2%, p < 0.001) and a higher Hb concentration (142 +/- 16 versus 101 +/- 8 g.L-1, p < 0.001). The lower body mass in hypoxemic lambs (10.5 +/- 2.3 versus 13.0 +/- 2.8 kg) could be mainly accounted for by a decrease in intracellular water volume (4.7 +/- 1.3 versus 6.6 +/- 1.5 L, p < 0.01). Total body water (753 +/- 27 versus 780 +/- 40 mL.kg-1) and extracellular water volume (307 +/- 25 versus 277 +/- 15 mL.kg-1) in hypoxemic lambs were not significantly different from those in control lambs, but intracellular water volume was decreased (445 +/- 27 versus 501 +/- 35 mL.kg-1, p < 0.01). The ratio of extracellular to intracellular water volume was higher in hypoxemic lambs (0.69 +/- 0.10 versus 0.55 +/- 0.04, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8460064 TI - The influence of occlusion time on measuring respiratory resistance and compliance in infants with bronchiolitis. AB - The passive, single-breath, flow-volume technique is a simple method for measuring the resistance (Rrs) and the compliance (Crs) of the respiratory system in infants. So far, the potential influence of end inspiratory occlusion time on these measurements has not been investigated. We measured Rrs and Crs in 36 infants and toddlers with bronchiolitis; in each child, a spectrum of nine fixed occlusion times, ranging from 90 to 600 ms, was applied in random sequence. Increasing the duration of occlusions from 90 to 275 ms resulted in marked stepwise changes of measured Rrs and Crs; occlusions longer than 275 ms, however, produced highly reproducible measurements, as expressed 1) by minimal absolute differences between measured values at subsequent occlusion times and 2) by minimal percentage changes of measured values from one occlusion time to the next. There was no influence of age on the results; reproducible measurements were made in children as old as 1.5 y. This suggests that, in infants with bronchiolitis, 1) occlusions between 300 and 450 ms might be ideal for obtaining reliable measurements, and 2) the age range for applying this method can be extended into the 2nd y of life. PMID- 8460065 TI - Altered growth hormone secretory dynamics in prepubertal males with constitutional delay of growth. AB - We have used the technique of deconvolution analysis to determine if abnormalities in growth hormone (GH) secretion or metabolic clearance underlie the observed alterations in circulating hormone concentrations in a group of seven prepubertal males with constitutional delay of growth (SHORT-DBA). The results were compared with data obtained from 13 healthy, short prepubertal males (SHORT) and 11 healthy prepubertal male subjects of normal stature (NORMAL). Although the mean 12-h overnight GH production rates were invariant among the groups (8.0 +/- 1.0 versus 7.3 +/- 0.7 versus 6.7 +/- 1.2 micrograms/L, NORMAL versus SHORT versus SHORT-DBA for all comparisons), different secretory mechanisms were operative. The secretory burst half-duration (time interval of the secretory event at half-maximal amplitude) of the SHORT-DBA subjects (26 +/- 1 min) was greater (p = 0.02) than that of the SHORT group (20 +/- 1 min); values for both the SHORT and SHORT-DBA subjects were indistinguishable from that of NORMAL controls (22 +/- 2). Both the mass of GH released per secretory episode and the maximal rate of hormone secretion were less (p < or = 0.02 and the p < 0.01, respectively) for the SHORT-DBA subjects [16 +/- 2 micrograms/unit of body distribution volume (Lv) and 0.6 +/- 0.1 microgram/Lv/min, respectively] compared with those of the NORMAL (26 +/- 2 micrograms/L, and 1.1 +/- 0.1 micrograms/Lv/min, respectively) and SHORT (28 +/- 4 micrograms/Lv and 1.3 +/- 0.2 micrograms/Lv/min, respectively) groups; values for the latter two groups were indistinguishable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8460066 TI - E1 pyruvate dehydrogenase deficiency in a child with motor neuropathy. AB - We report the case of a boy who developed a motor neuropathy during infectious episodes at 18 mo and 3 y of age. When he was 7 y old, he suffered persistent weakness and areflexia; his resting lactate and pyruvate values were 3.65 mM and 398 microM, respectively (controls: 1.1 +/- 0.3 mM and 90 +/- 22 microM), and an exercise test demonstrated a lactic acidosis (13.6 mM; controls: 6.4 +/- 1.3 mM) with a high pyruvate level (537 microM; controls: 176 +/- 15 microM) and a low lactate/pyruvate ratio (24.2; controls: 35 +/- 2). The results of polarographic studies on muscle mitochondria suggested a defect in pyruvate oxidation (pyruvate 17 ng atom O/min/mg protein; controls: 115 +/- 42), whereas glutamate, palmitoylcarnitine, and succinate were good respiratory substrates. The activity of total pyruvate dehydrogenase complex (PDHC) in muscle mitochondria and in fresh mononuclear cells was markedly decreased (9.7 and 0.054 nmol 14CO2/min/mg protein, respectively; controls: 123 +/- 4.5 and 0.733 +/- 0.03, respectively). Immunochemical analysis in muscle mitochondria demonstrated an absence of the alpha and beta E1 PDHC subunits. After 2 y of treatment with 500 mg/d thiamine, the patient was clinically improved. A genetic study of the main regions of mutations (exon 10 and 11) in the X chromosome encoding for the E1 alpha subunit of PDHC did not show any mutation. These data indicate that, although genetically different, this case enters in a very rare category of patients with PDHC deficiency without cerebral dysfunction and improved by thiamine + L-carnitine therapy. PMID- 8460067 TI - Impairment of cerebral autoregulation during extracorporeal membrane oxygenation in newborn lambs. AB - This study was designed to evaluate the effect of normothermic partial bypass, or venoarterial extracorporeal membrane oxygenation (ECMO), on cerebral autoregulation. Fourteen newborn lambs, 1-7 d of age, were randomized into two groups: control (ligation of right carotid artery and jugular vein without ECMO; n = 7) and ECMO (ligation with placement on routine venoarterial ECMO at 120-150 mL/kg/min; n = 7). After 1 h of ECMO or stabilization in controls, cerebral autoregulation was evaluated by lowering cerebral perfusion pressure (CPP) by increasing intracranial pressure through infusion of artificial cerebrospinal fluid into the lateral ventricle. Four ranges of CPP were evaluated: 1) baseline, 2) 55-40, 3) 39-25, and 4) < 25 mm Hg. In ECMO animals, cerebral blood flow (CBF) decreased from baseline (39 +/- 7 mL/100 g/min) to 23 +/- 7 and 12 +/- 2 at CPP of 39-25 and < 25 mm Hg. In the control group, CBF was unchanged from baseline (48 +/- 11 mL/100 g/min) until CPP was < 25 mm Hg, at which time it decreased to 27 +/- 16 mL/100 g/min. Cerebral oxygen consumption decreased from baseline (4.2 +/- 1.1 mL/100 g/min) to 4.0 +/- 0.7 and 3.2 +/- 1.3 mL/100 g/min at CPP of 39-25 and < 25 mm Hg, respectively, in the ECMO group. In the control group, cerebral oxygen consumption was unchanged from baseline (4.2 +/- 1.1 mL/100 g/min) until CPP was reduced to < 25 mm Hg (3.2 +/- 1.3 mL/100 g/min). When CBF autoregulation was altered, i.e. when total CBF decreased, right-left hemispheric CBF differences were noted in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8460068 TI - Myocardial perfusion and performance after indomethacin administration in newborn lambs. AB - Indomethacin is a drug widely used to achieve pharmacologic closure of a patent ductus arteriosus in the premature infant. In several vascular beds (brain, kidney, intestine), indomethacin has been shown to cause vasoconstriction. Possible negative effects on myocardial blood flow and performance could be deleterious in premature infants with limited cardiac reserve. Before, during, and 30 and 60 min after administration of 1 mg.kg-1 of indomethacin in nine newborn lambs, we measured coronary blood flow velocity (Doppler flow probe around the left circumflex coronary artery), left ventricular (LV) pressure (by tip manometer) and volume (by conductance catheter technique), cardiac output, arterial pressure, arterial and venous saturations and calculated systemic and coronary vascular resistance, LV systolic function by the end-systolic pressure volume relationship, and myocardial oxygen extraction. To investigate the effect of indomethacin on the flow regulation of the coronary vascular bed, we measured coronary flow and LV function under different levels of myocardial demand, achieved by stepwise occluding of the descending aorta. During indomethacin infusion, coronary and systemic vascular resistance increased significantly (by 43 and 76%, respectively), resulting in an increase in arterial pressure from 10.2 to 16.9 kPa, whereas neither coronary flow nor LV systolic function changed despite the increase in afterload. Thirty and 60 min after indomethacin, coronary and systemic vascular resistance had returned to baseline levels and LV systolic function remained unchanged. The relationship between coronary flow and cardiac demand was not different before or after indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8460069 TI - In situ morphology of the aorta and common iliac artery in the fetal and neonatal rat. AB - In situ cross-sectional morphology of the ascending, descending, and abdominal aorta and the common iliac arteries was studied after rapid, whole-body freezing of fetal and neonatal rats. In the fetus, the ascending aorta was smaller than the descending aorta and the abdominal aorta was relatively large, continuing to the large right common iliac artery and the umbilical artery. After birth, the umbilical artery and the ductus arteriosus closed rapidly, and the size of the aorta changed within a few days. The ascending aorta became larger than the descending aorta in 2 d, and the abdominal aorta became smaller, especially at the infrarenal part. The right common iliac artery, which continues to the umbilical artery in fetal life, became smaller, and its diameter was the same as that of the left common iliac artery 2 d after birth. PMID- 8460070 TI - Diversity of immunoglobulin light chain usage in the human immune response to Haemophilus influenzae type b capsular polysaccharide. AB - The response to the capsular polysaccharide of Haemophilus influenzae type b (Hib PS) has been used to determine the molecular basis of antibody gene diversity in humans. In contrast to the relatively restricted nature of anti-Hib PS heavy chain variable region gene expression, a variety of light-chain variable region genes may encode this antibody (Ab) response. Light-chain variable region gene usage appears to determine the expression of certain Ab idiotypes and fine antigen specificity. To further define the role of light-chain variable region gene usage in important anti-Hib PS Ab subgroups, we have cloned and sequenced a number of immunoglobulin light-chain variable region genes (IgVL) from human monoclonal IgA anti-Hib PS Ab generated in response to Hib PS-protein conjugate vaccines. Three of these Ab are encoded by unusual variable segments. One kappa Ab is encoded by the "predominant" V kappa II A2 germline gene but, in contrast to a previously reported A2-encoded IgVL sequence, differs from the A2 germline sequence. The IgVL sequence of a second Ab is the only sequence of a kappa-Ab that cross-reacts with the structurally related antigen Escherichia coli K100 polysaccharide reported to date. This IgVL is encoded by a V kappa III-segment most closely homologous to the Humhv328/L16 germline gene, whereas previous reports suggested V kappa III-encoded anti-Hib PS Ab might be exclusively encoded by the germline gene Humhv325/A27.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8460071 TI - Acute interstitial nephritis. Why do the kidneys suddenly fail? AB - Acute interstitial nephritis is a clinical and pathologic entity with diverse causes. The most common cause at present is reaction to drug use, but infection, a concomitant uveitis syndrome, and other rare causes have been reported. Acute interstitial nephritis should always be considered in a patient with acute renal failure, because it is a treatable cause that may result in interstitial fibrosis and irreversible disease if not arrested. PMID- 8460072 TI - Using spirometry in the primary care office. A guide to technique and interpretation of results. AB - Spirometry is important in evaluating patients with respiratory complaints and helpful in following the course of disease. The American Thoracic Society encourages office use of spirometry and has published guidelines and minimum standards to promote accurate and appropriate testing. Equipment designed to meet these standards is available for office use, and peak flowmeters are available for home use by selected patients. When performed correctly and interpreted in the context of other clinical data, spirometry may identify reductions in flow (obstruction) or volume (restriction). Characteristics of the flow-volume loop may suggest specific types of upper or large airways obstruction. Serial monitoring of forced expiratory volume in 1 second in chronic obstructive pulmonary disease and of peak expiratory flow rate in asthma may help guide medical therapy. When spirometry fails to detect or completely characterize impairment of lung function, more extensive testing in a pulmonary function laboratory is indicated. PMID- 8460073 TI - Otitis media in children. Medical versus surgical treatment. AB - Much controversy surrounds the subject of proper management of chronic otitis media in children. Treatment options include medical management with antibiotics and steroids as well as insertion of tympanostomy tubes. In some children with recurrent or persistent middle-ear infections, prophylactic treatment with antibiotics is indicated. Although medical treatment compares favorably with surgical treatment, tubes significantly decrease the frequency of episodes of acute otitis media. Treating children medically for 2 to 3 years while they "grow out of their problem" ignores the hardship of the family that has to care for a sick child. More important, it forces the child into an existence of medications and recurrent infections. An open mind about all treatment options is essential when deciding on the best therapy for a particular child. PMID- 8460074 TI - Going home. PMID- 8460075 TI - Insights about pathological gamblers. 'Chasing losses' in spite of the consequences. AB - In the United States, a small but growing portion of the adult population are pathological gamblers. The majority are men (about one third are women). Although the Diagnostic and Statistical Manual of Mental Disorders, third revised edition, defines pathological gambling as a disorder of impulse control, diagnostic criteria and treatment are modeled after psychoactive substance dependence. About half of pathological gamblers have a history of alcoholism or substance abuse, and accompanying mood disorders (eg, major depression, bipolar disorder) are common. Once diagnosed, pathological gambling is highly treatable. PMID- 8460076 TI - Hematologic emergencies. Management of transfusion reactions and crises in sickle cell disease. AB - Two hematologic emergencies are reviewed in this article: transfusion reactions and crises in patients who have sickle cell disease. Transfusion reactions may be due to incompatibility, IgA deficiency, allergy or, rarely, bacterial contamination of the blood product. A major hemolytic reaction due to incompatibility may progress to hypotension and shock. To prevent this type of reaction, blood products should be given only when necessary and attention should be given to eliminating clerical errors, which are responsible for many hemolytic reactions. In patients with sickle cell disease, a painful crisis due to vascular occlusion is the most common emergency. Rehydration is essential, and narcotics may be needed to relieve pain. Aplastic crisis is managed by transfusion of packed red blood cells and supportive care. Sickle cell crisis may affect major organ systems. The acute chest syndrome can be complicated by pneumonia; rapid respiratory failure may occur if multiple lobes are involved. Splenic or hepatic sequestration requires aggressive rehydration and transfusion. In patients who have had stroke or subarachnoid hemorrhage, a long-term exchange transfusion program is needed to keep hemoglobin S levels below 30%. PMID- 8460077 TI - Hematologic emergencies. Management of hyperleukocytic syndrome, DIC, and thrombotic thrombocytopenic purpura. AB - Three hematologic emergencies are reviewed in this article: the hyperleukocytic syndrome, disseminated intravascular coagulopathy (DIC), and thrombotic thrombocytopenic purpura (TTP). The hyperleukocytic syndrome most commonly occurs in patients with acute myelogenous leukemia. It commonly affects the lungs and may cause intracranial hemorrhage. Long-term control is accomplished only by inducing a remission of the leukemia. Patients with DIC may have excessive clotting, uncontrolled bleeding, or both. Infections are the most common cause; cases in obstetric patients are usually due to abruptio placentae or retained dead fetus. Any acute leukemia can cause DIC. The underlying disorder is the usual cause of death. TTP is thought to be due to a substance or substances in the plasma that initiate marked platelet aggregation in the microcirculation. It affects persons of any age and either sex. Plasmapheresis is the preferred treatment. PMID- 8460078 TI - Role of aldosterone in congestive heart failure. AB - Antialdosterone therapy in patients with secondary hyperaldosteronism due to myocardial failure must accomplish the following: (1) reduce or preferably normalize plasma aldosterone levels by blockade of excessive synthesis, (2) antagonize the renal and systemic effects of aldosterone at its receptor sites, and (3) minimize the presence of multiple stimuli to aldosterone secretion. Fulfillment of these goals likely requires the blockade of angiotensin II-induced aldosterone secretion (ie, angiotensin-converting enzyme inhibition) with an antagonist of aldosterone receptors (ie, spironolactone [Aldactone]). Despite the potential for hyperkalemia with this combined use of medications, particularly in patients with impaired renal function, such therapy is likely to attenuate the salt-acquisitive state that is characteristic of myocardial failure. PMID- 8460079 TI - Topical corticosteroid 'addiction'. A cause of perioral dermatitis. AB - Acne rosacea, perioral dermatitis, and telangiectasia are all local side effects that can flare up when potent topical corticosteroids used on the face are withdrawn. The two cases of perioral dermatitis described here illustrate the nature of the addictive cycle caused by long-term use of these agents. To prevent side effects of topical corticosteroids used on the face, physicians need to avoid long-term prescriptions and shun superpotent agents entirely for this area. Pharmacists should not refill topical corticosteroid prescriptions without authorization. Patient education must emphasize the transient nature of flare-ups of itching and rash that occur when these agents are withdrawn. Systemic and topical antibiotics and corticosteroid-free antipruritics are the mainstays of therapy. PMID- 8460080 TI - Endocarditis. Changing trends in epidemiology, clinical and microbiologic spectrum. AB - Infective endocarditis refers to infection of the endocardium or heart valves by microbes, resulting in tissue destruction. Clinical presentation is quite variable, and a high level of suspicion is essential for recognition. Diagnosis is dependent on identification of the causative agent in blood cultures. Cultures that are persistently negative indicate the presence of culture-negative endocarditis, and diagnosis is one of exclusion. Treatment of endocarditis consists of high doses of antibiotics active against the infecting organism. Individualized therapy is the key to management. PMID- 8460081 TI - Coping with achalasia. AB - Achalasia is a primary esophageal motor disorder that is characterized by dysphagia, regurgitation, and chest pain. The diagnosis is suggested by narrowing with the classic "bird's beak" appearance of the distal esophagus. Esophageal manometry showing aperistalsis confirms the diagnosis. Pseudo-achalasia must be excluded with endoscopy. Pneumatic dilatation is the treatment of choice. Surgical myotomy is reserved for patients in whom repeated pneumatic dilatation fails. PMID- 8460082 TI - Common gynecologic problems after age 75. AB - Management of gynecologic problems in women aged 75 and over can be challenging. Appropriate examination and evaluation differs from that for younger women, and these patients are often poor surgical candidates. The most common presenting conditions include stress incontinence, atrophic changes of the vulva and vagina, and pelvic relaxation with uterine prolapse. Several techniques for nonsurgical management are available, including topical and systemic drug therapy and use of products and aids that increase comfort and encourage independence. PMID- 8460084 TI - AIDS information resource. PMID- 8460083 TI - Dental amalgam and neuropsychological dysfunction. PMID- 8460085 TI - Urinary tract infection. How has its management changed? AB - In patients with apparent urinary tract infection, clinical presentation and results of physical examination and a few simple laboratory studies can identify patients who need urine culture and/or imaging studies and can guide initial therapy. A wide variety of effective antibiotics are available for various causes, and local patterns of microbial sensitivity and cost-effectiveness help govern drug selection. Response to therapy governs further treatment and follow up. Exclusion of complicated infection and particular risk factors permits simplified but effective management of symptomatic recurrent infections. PMID- 8460086 TI - Diabetic nephropathy. What you need to know to preserve kidney function. AB - Patients with diabetes who have a family history of cardiovascular disease or hypertension are at greatly increased risk for development of diabetic nephropathy. The changes that occur in the diabetic hypertensive kidney (mesangial matrix expansion, altered charge and size selectivity of the glomerular basement membrane, and significantly increased intraglomerular pressure) are not generally present in the nondiabetic hypertensive kidney. Angiotensin-converting enzyme (ACE) inhibitors and nondihydropyridine calcium blockers are known to attenuate these changes. Patients taking these agents experience a reduction in the proteinuria associated with nephrotic syndrome; this is accompanied by marked reductions in serum cholesterol level, increases in serum albumin level, and reduced morbidity. Other antihypertensive therapies have not been shown to have these effects. Moreover, ACE inhibitors and alpha blockers have been shown to improve insulin resistance in patients with noninsulin dependent diabetes. For the patient with diabetes, attention must be given to these factors, and blood pressure medication must be carefully selected. PMID- 8460087 TI - Clinical features and natural history of central cavitary necrosis. AB - Central cavitary necrosis (CCN) is an unusual complication of acute pancreatitis in which the necrosis is confined almost entirely to the pancreatic parenchyma and there is little if any extrapancreatic necrosis. In our experience with 10 patients with CCN, clinical features suggested that the episodes of acute pancreatitis were initially severe, with high Ranson scores (mean, 4.2; range, 1 6), development of systemic complications, computed tomography (CT) grade of D or E by the Balthazar-Ranson scoring system, need for intensive care unit admission in 8 of 10 patients, and mean length of hospitalization of 56 days (range, 28-153 days). However, the incidence of infection was low (20%) and mortality was also low (10%). Factors that help explain a favorable prognosis were low APACHE-II scores at admission and at 48 h, absence of shock, paucity of extrapancreatic necrosis, and rapid resolution of clinical toxicity prior to the diagnosis of CCN by CT scan at a mean of 19.8 days (range, 9-63 days) after the onset of symptoms. Surgical debridement is indicated for complications such as secondary infection and ongoing pain. In the absence of complications, an attempt should be made to treat CCN medically. PMID- 8460088 TI - Clinical presentation and ultrasonography in the diagnosis of pancreatic cancer. AB - One thousand twenty patients consecutively admitted because of a clinical suspicion of pancreatic cancer were investigated to evaluate the accuracy of simple clinical, laboratory, and ultrasonographic data in the diagnosis of pancreatic cancer. Age, weight loss, recent-onset diabetes mellitus, palpable abdominal mass or gallbladder, elevated serum bilirubin or alkaline phosphatase levels, and ultrasonography were significant criteria in discriminating 80 pancreatic cancers from 940 controls. The most sensitive criteria were ultrasonography (83%), weight loss (66%), and bilirubin level of > 3 mg/dl (61%); the most specific were ultrasonography (99%), recent-onset diabetes (97%), and a distended palpable gallbladder (94%). Only ultrasonography demonstrated an elevated positive predictive value (86%), while weight loss, elevated bilirubin and alkaline phosphatase, besides ultrasonography had an elevated negative predictive value (95%). These results show that advanced pancreatic cancer may be excluded with simple clinical and laboratory data; ultrasonography can confirm the diagnosis with a high degree of accuracy. We suggest that the results of any new diagnostic tests for pancreatic cancer be compared with these clinical findings. PMID- 8460089 TI - Diagnostic significance of cancer-associated carbohydrate antigen (CA19-9) concentrations in pancreatic juice: analysis in pure pancreatic juice collected by endoscopic aspiration and immunohistochemical study in chronic pancreatitis. AB - This study evaluated the diagnostic significance of concentrations of the cancer associated carbohydrate antigen CA19-9 in pure pancreatic juice (PPJ) collected by endoscopic cannulation. We also attempted to elucidate the features and source of the increased CA19-9 concentration found in the pancreatic juice of patients with chronic pancreatitis (CP) by means of immunohistochemical staining. The mean output as well as the mean concentration of CA19-9 in each of the four fractions collected was highest in patients with pancreatic cancer (PC) and also was elevated significantly in patients with CP compared with controls. However, CA19 9 concentrations were not elevated in patients with cholecystolithiasis. When the cutoff value was set as the mean concentration + 2SD of the controls, significantly elevated concentrations of CA19-9 were found in the third fraction (secretory phase) in 90% of the patients with PC and 66% of the patients with CP. Immunohistochemical staining revealed that CA19-9 was expressed more widely in the ductal cells of CP tissues than in those of normal pancreatic (NP) tissues, with CP tissue showing more CA19-9-positive ductal cells per area than NP tissues. In NP tissue, CA19-9 was localized to the apical surface and supranuclear regions (apical type) in all the ductal cells stained by the antigen, while approximately 50% of cases with CP exhibited a cytoplasmic pattern showing a loss of polarity of the antigen expression. Moreover, this cellular localization pattern was more pronounced in the small ducts that had proliferated and aggregated following the destruction of lobules in CP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8460090 TI - Serum levels of CA 19-9 and CA 50 in relation to Lewis blood cell status in patients with malignant and benign pancreatic disease. AB - Serum expression of the cancer-associated antigens CA 19-9 and CA 50 and their relation to Lewis blood cell status were studied in 26 patients with pancreatic duct carcinoma and 26 patients with pancreatitis. The discriminating capacity between benign and malignant disease was high for both tumor markers. The correspondence between serum levels of CA 19-9 and CA 50 was close irrespective of the Lewis phenotype of the patient. All cancer patients with normal levels of CA 19-9 and CA 50 were of the phenotype Le(a-b-). Knowledge of the Lewis phenotype may therefore add vital information when tumor marker assays are used for diagnosis and monitoring of malignant pancreatic disease. PMID- 8460091 TI - The protein core of the NCA-related pancreatic adenocarcinoma-associated antigen (DD9-Ag) is NCA-50. AB - Earlier studies with monoclonal antibody (mcAb) DD9E7 have identified a family of nonspecific cross-reacting antigen (NCA)-related antigens that are highly expressed in human pancreatic adenocarcinoma. To analyse the molecular nature of these glycoproteins further, a lambda gt11 expression library has been constructed from the GER pancreatic adenocarcinoma cell line and screened with an NCA sequence-specific oligonucleotide probe. Sequence analysis and restriction enzyme mapping of the clones isolated have shown that they are all homologous with the NCA-50 protein core sequence rather than other related members of the carcinoembryonic antigen/NCA gene family. With use of the same probe, a 2.5-kb mRNA transcript, characteristic of NCA-50, was found in pancreatic adenocarcinoma tumour samples. This study suggests that the 80- to 115-kDa glycoproteins, which we had previously identified in pancreatic adenocarcinomas with NCA-specific mcAb DD9E7, are the result of aberrant glycosylation of the NCA-50 protein core following cell transformation. PMID- 8460092 TI - Organophosphate sensitizes the human pancreas to acinar cell injury: an ultrastructural study. AB - Viable pancreas fragments from five human donors were incubated in oxygenated buffered Eagle Medium. The preparation and incubation conditions were based on the method of Scheele and Palade. In Group 1 there was 1-h preincubation with echothiophate (10(-4) M); then, acetylcholine (10(-5) M) was added. After 2 h tissues were prepared for electron microscopy. Acinar injury with vacuole formation was apparent. Many of these changes were observed in fragments incubated only with acetylcholine (10(-5) M) (Group 2) and in incubates with echothiophate only (10(-4) M) (Group 3); only minor changes were seen in controls with Eagle's Medium (Group 4). Large vacuoles were significantly more numerous in Group 1 than in Control Group 4 (p < 0.05). Zymogen granules were depleted in Groups 1, 2, and 3. This depletion was significant in Group 1 when compared with Group 4 (p < 0.02). These results extend previous in vitro results that showed increased amylase release after echothiophate treatment in human pancreas and a left shift in response to acetylcholine. PMID- 8460093 TI - Morphologic and functional evaluation of the exocrine pancreas in beta thalassemia major. AB - Thirty-nine consecutive patients with beta-thalassemia major and iron overload were studied by ultrasonography and serum pancreatic enzyme determination to assess the frequency and characteristics of pancreatic damage in this condition. The results were compared with those of a matched group of healthy controls. Most of the thalassemic patients had a markedly increased echogenicity of the pancreas and decreased size of the gland (p < 0.001 for both features as compared with controls). Both echogenicity and decreased size of the gland were significantly correlated (p < 0.001) with patient age and duration of transfusional therapy. Serum concentrations of trypsin and lipase were significantly lower (p < 0.02) in patients than in controls. The lowest enzyme values were found in older patients with longer duration of transfusional therapy, who also had the most marked sonographic changes. The results suggest that the exocrine pancreas is structurally and functionally damaged in the majority of thalassemic patients with iron overload. PMID- 8460094 TI - Assay of trypsinogen activation in the cat experimental model of acute pancreatitis. AB - An enzyme-linked immunosorbent assay for trypsinogen activation peptide (TAP) was used to measure urinary TAP levels in standard feline models of acute oedematous pancreatitis and acute haemorrhagic pancreatitis. It has been shown that the extent of pancreatic damage as assessed histologically is significantly greater in the model of acute haemorrhagic pancreatitis. This increase in damage has been found to be associated with a significantly greater increase in the excretion of urinary TAP. PMID- 8460095 TI - Physiological characteristics of spontaneously developed diabetes in male WBN/Kob rat and prevention of development of diabetes by chronic oral administration of synthetic trypsin inhibitor (FOY-305). AB - The male WBN/Kob rats spontaneously develop diabetes mellitus with age. In this study, we examined how glucose tolerance, potency of insulin release, and histology of the pancreas were changed with age in this model. Furthermore, we examined the effect of FOY-305, a synthetic trypsin inhibitor, on this model. Male WBN/Kob rats were divided into two groups: one group fed on standard pellet diet (STD group) and the other on pellet containing 0.1% FOY-305 (FOY group) for 56 weeks after age 4 weeks. Oral glucose (2 g/kg) tolerance test, histology of the pancreas, and glucose (8.3 mM)- and arginine (10 mM)-stimulated insulin release from the isolated perfused pancreas were examined at 8, 20, 40, and 60 weeks of age in both groups. Pancreatic insulin content was examined at 60 weeks. In the STD group, impairment of glucose tolerance and destruction and fibrosis of pancreatic tissues progressed with age. Glucose-stimulated insulin release was remarkably reduced with age, while arginine-stimulated insulin release was preserved. By contrast, in the FOY group, development of glucose intolerance was delayed and the pancreas showed fewer pathologic changes compared with the STD group. Insulin releases in response to both glucose and arginine were preserved at all ages examined. Total pancreatic insulin content at 60 weeks of age was significantly greater than that of the STD group. The male WBN/Kob rat is a new type of diabetic model that shows a similar pattern of insulin release to that in rat with non-insulin-dependent diabetes mellitus and also shows unique histopathological changes in exocrine pancreas. FOY-305 was effective in preventing the development of diabetes in this model, although its mechanism is still unknown. PMID- 8460096 TI - Inhibition of growth of a transplanted rat pancreatic acinar carcinoma with CCK 8. AB - Gastrointestinal hormones and neuropeptides are known to regulate growth of various normal gastrointestinal tissues and many cancers. Since cholecystokinin (CCK) is considered the most potent trophic factor for the exocrine pancreas, we studied its effect on growth of an acinar cell tumor, initially induced by azaserine and transplanted to the rat, in comparison with the normal pancreas. When tumors became palpable, rats were treated three times daily for 12 or 14 days with CCK-8 or NaCl 0.9% (controls) alone or in combination with the CCK receptor antagonist CR1409 (10 mg/kg) administered subcutaneously twice daily. Then tumors and pancreata were analyzed for their size, composition, and CCK receptors. Tumor volume, weight, and protein content, RNA, DNA, and enzymes decreased after CCK-8 treatment in a dose-dependent manner, the maximal effect being observed with 4-micrograms/kg treatment. This inhibitory effect was partially suppressed by CR1409, which by itself also reduced tumor growth, but to a lesser degree. CCK-8 exerted a stimulating effect on growth of the normal pancreas with low doses (1 and 2 micrograms/kg) and an inhibitory effect or no effect with a higher dose (4 micrograms/kg). CR1409 prevented this latter effect, but did not affect by itself the normal pancreas. These findings suggest that CCK 8 inhibits growth of an acinar cell tumor grafted to the rat; this effect is mediated by the occupation of specific CCK receptors present in high density on these cells. In contrast, CCK-8 exerts a biphasic effect on the normal pancreas as a function of its dose. PMID- 8460097 TI - Effect of a new synthetic trypsin inhibitor on taurocholate-induced acute pancreatitis in rats. AB - The effect of a novel synthetic trypsin inhibitor, 4-sulfamoylphenyl 4 guanidinobenzoate methanesulfonate (ONO-3307), on severe acute pancreatitis was studied by changing its timing, frequency, and dose in trypsin-taurocholate induced acute experimental pancreatitis in rats. Rats were divided into four groups according to difference of ONO-3307 administration: group A, 2 mg/0.5 ml of ONO-3307 s.c. 1 h before and after induction of pancreatitis; group B, 2 mg/0.5 ml s.c. 1 and 3 h after; group C, 4 mg/1 ml s.c. 1 h before; group D, 4 mg/1 ml s.c. 1 h after. The survival rate at 24 h was significantly improved in group A (75% in A vs. 17% in control; p < 0.01) and in group B (57 vs. 29%; p < 0.05), but not in group C or D. Amylase and immunoreactive trypsin in serum and ascites of the treated were significantly lower than those of controls in both groups A and B. The survival rates were improved dose dependently when ONO-3307 was administered 1 h before and after induction of pancreatitis. ONO-3307 showed favorable effects on the initial stage of severe acute pancreatitis when given in divided doses to maintain the effective serum levels. PMID- 8460098 TI - Isolation, culture, and characterization of human pancreatic duct cells. AB - To establish a suitable control for pancreatic tumor cell lines, we have isolated and cultured primary human pancreatic duct cells from transplant donors. Duct cells were isolated by dissecting the main pancreatic duct and first-degree branches and enzymatic digestion. Aggregates of cells were cultured for 1 up to 5 weeks and monitored for changes in morphology and growth by phase contrast microscopy. Contaminating fibroblasts were mechanically removed from day 4 on and by cloning of epithelial cells. Cultured cells were characterized by phase contrast microscopy, electron microscopy, and immunofluorescence with antibodies against intermediate filaments (cytokeratins, vimentin, desmin), mucins (Du-Pan 2, CA 19-9), carbonic anhydrase II, acinar cell enzymes (amylase, lipase, trypsin), and islet cells. About 90% of the cultured cells could be identified as ductal epithelial cells by their expression of cytokeratins, mucins, and carbonic anhydrase II. These cells showed the ultrastructural features of duct cells. After 3-5 weeks of culture, most of the cultured cells showed co-expression of cytokeratins and vimentin in addition to duct cell markers. About 10% of cells were contaminating fibroblasts (vimentin positive, cytokeratin negative). The cultured normal human duct cells as the postulated cells of origin of the pancreatic adenocarcinoma may serve as a useful control for cultured pancreatic tumor cell lines. PMID- 8460099 TI - In vitro stimulation of hamster pancreatic duct growth by an extract derived from the "wrapped" pancreas. AB - Partial obstruction of the hamster pancreas in the cellophane wrap model leads to the induction of duct and ductular proliferation followed by endocrine cell differentiation. This effect appears to be mediated by the local action of a growth factor. The purpose of the present study was to determine if cytosolic extract prepared from the wrapped pancreas had trophic activity on purified hamster pancreatic ductal epithelium in tissue culture. Cultures of purified pancreatic ducts were prepared by digestion of the hamster pancreas using a solution of collagenase type XI and chymotrypsin infused directly into the pancreatic duct. The ducts were separated and purified by a series of steel mesh filtrations. Ducts were embedded in 1.5% Seaplaque agarose and fed a liquid medium containing serum-free Dulbecco's Modified Eagle Medium/Nutrient Mixture F 12 Ham (DME/F-12), 12.5% cytosol extract+DME/F-12, or 25% cytosol extract+DME/F 12. The trophic effect of the extract on the tissue in culture was evaluated by the incorporation of tritiated thymidine ([3H]TdR) into DNA. Duct fragments cultured in medium supplemented with 12.5% cytosol showed no difference in their [3H]TdR uptake compared with control ducts (908 +/- 147 vs. 913 +/- 151 dpm/micrograms DNA). The incorporation of [3H]TdR by ducts maintained in medium supplemented with 25% cytosol extract was increased 78% over serum-free controls (1,632 +/- 386 vs. 913 +/- 147 dpm/micrograms DNA; p < 0.025). We conclude that a cytosol extract prepared from the partially obstructed cellophane-wrapped pancreas contains a factor(s) trophic for pancreatic ductal cells. PMID- 8460100 TI - Molecular form of islet amyloid polypeptide (amylin) released from isolated rat islets of Langerhans. AB - Islet amyloid polypeptide (IAPP) is a 37-amino acid residue polypeptide, originally isolated from the pancreatic amyloid deposits of patients with type II diabetes mellitus. Subsequently, IAPP was found to be colocalised with insulin in beta-cell secretory granules of the normal mammalian pancreas. Recently, IAPP has been reported to inhibit glucose-stimulated insulin release from isolated rat islets and to be released in response to glucose and arginine. To investigate further the regulation of IAPP release from the islet, we used a previously developed specific radioimmunoassay for IAPP and measured IAPP secretion from isolated rat islets of Langerhans. Release of IAPP-like immunoreactivity (-LI) was stimulated by glucose: 3.3 +/- 0.3, 3.9 +/- 0.3, and 11.1 +/- 1.5 (n = 5, mean +/- SEM) fmol/islet/60 min at 2, 7, and 20 mM, respectively. Carbachol (0.1 mM) increased the release of IAPP-LI at the lower glucose concentrations: 8.1 +/- 0.9, 8.7 +/- 0.6, and 11.7 +/- 1.8 fmol/islet/60 m in at 2, 7, and 20 mM glucose. Somatostatin (1 microM) suppressed glucose-stimulated IAPP-LI release (17.5 +/- 1.5 vs. 5.1 +/- 0.5 fmol/islet/60 min). Chromatographic characterisation of the IAPP-LI released into the incubation medium revealed two immunoreactive forms: The major peak (74% of the total IAPP-LI) corresponded to synthetic IAPP-37, while a smaller form, comprising 26% IAPP-LI, eluted later. In acid extracts of islets, all (> 95%) immunoreactivity co-eluted with the synthetic IAPP. PMID- 8460101 TI - Metabolism of insulin and glucagon in liver and pancreas in dogs with obstructive jaundice. AB - Insulin and glucagon metabolism in the pancreas with obstructive jaundice caused by complete ligation of the common bile duct and in the cholestatic liver caused by hepatic duct ligation was evaluated experimentally using dogs. The isolated perfused pancreas in obstructive jaundiced dogs, which showed a low insulin response in the peripheral blood after intravenous glucose administration, revealed depression of insulin production and no change of glucagon production in response to cholecystokinin octapeptide. The extraction of insulin in the cholestatic lobe of the liver was decreased compared with that in the noncholestatic lobe. The extraction of glucagon, on the other hand, in the cholestatic lobe and in the noncholestatic lobe showed no significant difference. So the imbalance of glucose metabolism in obstructive jaundice does not depend on the enhanced extraction of insulin in the liver, but on the depression of insulin production in the pancreas. PMID- 8460102 TI - Spontaneous resolution of a pancreatic pseudocyst 10 years after detection documented by ultrasound. PMID- 8460103 TI - Pancreatic schwannoma. PMID- 8460104 TI - The pancreas as the solitary site of metastasis from melanoma. PMID- 8460105 TI - Crystallographic analysis of the interaction between cyclosporin A and the Fab fragment of a monoclonal antibody. AB - The structure of the complex between cyclosporin A and the Fab fragment of a monoclonal antibody has been established by crystallographic analysis to 2.65 A resolution. The structure has been solved by molecular replacement using a composite Fab model. The current R-factor after refinement is 0.179 between 8 and 2.65 A resolution. The antibody is one among three known structures with long H3 loops. This loop conformation is observed for the first time in the presence of the antigen. Residues from all six hypervariable loops interact with cyclosporin A. However, the 17 residues long loop H3 is the main contributor to the buried combining site area and to the van der Waals contacts made with cyclosporin A, with 52 and 63%, respectively, of the total contribution. PMID- 8460106 TI - Effect of end group blockage on the properties of a class A amphipathic helical peptide. AB - In a recent classification of biologically active amphipathic alpha-helixes, the lipid-associating domains in exchangeable plasma apolipoproteins have been classified as class A amphipathic helixes (Segrest, J.P., De Loof, H., Dohlman, J.G., Brouillette, C.G., Anantharamaiah, G.M. Proteins 8:103-117, 1990). A model peptide analog with the sequence, Asp Trp Leu Lys Ala Phe Tyr Asp Lys Val Ala Glu Lys Leu Lys Glu Ala Phe (18A), possesses the characteristics of a class A amphipathic helix. The addition of an acetyl group at the alpha-amino terminus and an amide at the alpha-carboxyl terminus, to obtain Ac-18A-NH2, produces large increases in helicity for the peptide both in solution and when associated with lipid (for 18A vs Ac-18A-NH2, from 6 to 38% helix in buffer and from 49 to 92% helix when bound to dimyristoyl phosphatidylcholine in discoidal complexes). Blocking of the end-groups of 18A stabilizes the alpha-helix in the presence of lipid by approximately 1.3 kcal/mol. There is also an increase in the self association of the blocked peptide in aqueous solution. The free energy of binding to the PC-water interface is increased only by about 3% (from -8.0 kcal/mol for 18A to -8.3 kcal/mol for Ac-18A-NH2). The Ac-18A-NH2 has a much greater potency in raising the bilayer to hexagonal phase transition temperature of dipalmitoleoyl phosphatidylethanolamine than does 18A. In this regard Ac-18A NH2 more closely resembles the behavior of the apolipoprotein A-I, which is the major protein component of high-density lipoprotein and a potent inhibitor of lipid hexagonal phase formation. The activation of the plasma enzyme lecithin: cholesterol acyltransferase by the Ac-18A-NH2 peptide is greater than the 18A analog and comparable to that observed with the apo A-I. In the case of Ac-18A NH2, the higher activating potency may be due, at least in part, to the ability of the peptide to micellize egg PC vesicles. PMID- 8460108 TI - Theoretical studies of relaxation of a monomeric subunit of HIV-1 protease in water using molecular dynamics. AB - The dynamic behavior of one 99-residue subunit of the dimeric aspartyl protease of HIV-1 was studied in a 160 psec molecular dynamics simulation at 300 K in water. The crystal structure of one of the identical subunits of the dimer was the starting point, with the aqueous phase modeled by 4,331 explicit waters in a restrained spherical droplet. Analysis of the simulations showed that the monomer displayed considerable flexibility in the interfacial portions of the flap (the region which folds over the substrate), the N- and C-termini, and, to a lesser extent, the active site. The flap undergoes significant motion as an independent rigid finger, but without the cantilever previously reported in a simulation of the dimer. The N-terminus displayed the greatest fluctuational disorder whereas the C-terminus exhibited the greatest root mean square movement from the crystal structure. The central core of the monomer had a heavy-atom root mean square deviation from the initial structure of about 3.0 A during the latter half of the simulation. Although this is larger than the 1.6 A found for comparable simulations of typical globular proteins, the general features of the tertiary structure were preserved over the course of the simulation. Overall, these results indicate that the relaxed structure obtained in these simulations may provide a better model for the tertiary structure of the solvated HIV-1 protease monomer than the subunit conformation seen in the X-ray crystallographic structure of the dimer. Except in the flap region, the design of compounds intended to interfere with dimerization should take this relaxation and the flexibility of the solvated monomer, especially at the termini, into account. PMID- 8460107 TI - Theoretical probes of conformational fluctuations in S-peptide and RNase A/3'-UMP enzyme product complex. AB - The dynamic properties of the RNase A/3'-UMP enzyme/product complex and the S peptide of RNase A have been investigated by molecular dynamics simulations using suitable generalization of ideas introduced to probe the energy landscape in structural glasses. We introduce two measures, namely, the kinetic energy fluctuation metric and the force metric, both of which are used to calculate the time needed for sampling the conformation space of the molecules. The calculation of the fluctuation metric requires a single trajectory whereas the force metric is computed using two independent trajectories. The vacuum MD simulations show that for both systems the time required for kinetic energy equipartitioning is surprisingly long even at high temperatures. We show that the force metric is a powerful means of probing the nature and relative importance of conformational substates which determine the dynamics at low temperatures. In particular the time dependence of the non-bonded force metric is used to demonstrate that at low temperatures the system is predominantly localized in a single cluster of conformational substates. The force metric is used to show that relaxation of long range (in sequence space) interactions must be mediated by a sequence of local dihedral angle transitions. We also argue that the time needed for compact structure formation is intimately related to the time needed for the relaxation of the dihedral angle degrees of freedom. The time for non-bonded interactions, which drive protein molecules to fold under appropriate conditions, to relax becomes extremely long as the temperature is lowered suggesting that the formation of maximally compact structure in proteins must be a very slow process. PMID- 8460109 TI - "Ensemble" iterative relaxation matrix approach: a new NMR refinement protocol applied to the solution structure of crambin. AB - The structure in solution of crambin, a small protein of 46 residues, has been determined from 2D NMR data using an iterative relaxation matrix approach (IRMA) together with distance geometry, distance bound driven dynamics, molecular dynamics, and energy minimization. A new protocol based on an "ensemble" approach is proposed and compared to the more standard initial rate analysis approach and a "single structure" relaxation matrix approach. The effects of fast local motions are included and R-factor calculations are performed on NOE build-ups to describe the quality of agreement between theory and experiment. A new method for stereospecific assignment of prochiral groups, based on a comparison of theoretical and experimental NOE intensities, has been applied. The solution structure of crambin could be determined with a precision (rmsd from the average structure) of 0.7 A on backbone atoms and 1.1 A on all heavy atoms and is largely similar to the crystal structure with a small difference observed in the position of the side chain of Tyr-29 which is determined in solution by both J-coupling and NOE data. Regions of higher structural variability (suggesting higher mobility) are found in the solution structure, in particular for the loop between the two helices (Gly-20 to Pro-22). PMID- 8460110 TI - Perturbation of Trp 138 in T4 lysozyme by mutations at Gln 105 used to correlate changes in structure, stability, solvation, and spectroscopic properties. AB - In order to correlate between spectroscopic and structural changes in a protein, the environment of Trp 135 in T4 lysozyme was deliberately perturbed by the replacement of Gln 105 with alanine (Q105A), glycine (Q105G), and glutamic acid (Q105E). In wild-type lysozyme, Trp 135 is buried, but the indole nitrogen is hydrogen-bonded to the side-chain of Gln 105. In the Q105G and Q105A mutant structures, the indole nitrogen becomes accessible to solvent. Crystallographic analysis shows that the structures of all of the mutants are similar to wild type. There are, however, distinct rearrangements of the local solvent structure in response to the new side-chains. There are also small but significant changes in the relative orientations of the two domains of the protein that appear to result from a series of small, concerted movements of side-chains adjacent to residue 105. Evaluation of the fluorescence and phosphorescence of the mutant proteins in terms of their observed three-dimensional structures shows that large spectral changes do not necessarily imply large changes in structure or in static solvent accessibility. Increases in polar relaxation about the excited state of tryptophan may be the result of only small increases in local dynamics or solvent exposure. 1H-NMR was also used to monitor the effects of the substitutions on Trp 138. In Q105E, but not in Q105G, Q105A and WT, the H epsilon chemical shift of Trp 138 is very pH-dependent, apparently reflecting the titration of Glu 105 which has a spectroscopically determined pKa of 6.0. The elevation of the pKa of Glu 105 in Q105E is also reflected in the pH dependence of the stability of this mutant. PMID- 8460111 TI - Packing and recognition of protein structural elements: a new approach applied to the 4-helix bundle of myohemerythrin. AB - We present a novel search strategy for determining the optimal packing of protein secondary structure elements. The approach is based on conformational energy optimization using a predetermined set of side chain rotamers and appropriate methods for sampling the conformational space of peptide fragments having fixed backbone geometries. An application to the 4-helix bundle of myohemerythrin is presented. It is shown that the conformations of the amino acid side chains are largely determined at the level of helix pairs and that superposition of these results can be used to construct the full bundle. The final solution obtained, taking into account restrictions due to the lateral amphiphilicity of the helices, differs from the native structure by only a 20 degrees rotation of a single helix. PMID- 8460112 TI - Novel mechanism-based substrates of dihydrofolate reductase and the thermodynamics of ligand binding: a comparison of theory and experiment for 8 methylpterin and 6,8-dimethylpterin. AB - Molecular dynamics simulation and free energy perturbation techniques have been used to study the relative binding free energies of the designed mechanism-based pterins, 8-methylpterin and 6,8-dimethylpterin, to dihydrofolate reductase (DHFR), with cofactor nicotinamide adenine dinucleotide phosphate (NADPH). The calculated free energy differences suggest that DHFR.NADPH.6,8-dimethylpterin is thermodynamically more stable than DHFR.NADPH.8-methylpterin by 2.4 kcal/mol when the substrates are protonated and by 1.3 kcal/mol when neutral. The greater binding strength of 6,8-dimethylpterin may be attributed largely to hydration effects. In terms of an appropriate model for the pH-dependent kinetic mechanism, these differences can be interpreted consistently with experimental data obtained from previous kinetic studies, i.e., 6,8-dimethylpterin is a more efficient substrate of vertebrate DHFRs than 8-methylpterin. The kinetic data suggest a value of 6.6 +/- 0.2 for the pKa of the active site Glu-30 in DHFR.NADPH. We have also used experimental data to estimate absolute values for thermodynamic dissociation constants of the active (i.e., protonated) forms of the substrates: these are of the same order as for the binding of folate (0.1-10 microM). The relative binding free energy calculated from the empirically derived dissociation constants for the protonated forms of 8-methylpterin and 6,8-dimethylpterin is 1.4 kcal/mol, a value which compares reasonably well with the theoretical value of 2.4 kcal/mol. PMID- 8460113 TI - Computer simulation of antibody binding specificity. AB - A Monte Carlo algorithm that searches for the optimal docking configuration of hen egg white lysozyme to an antibody is developed. Both the lysozyme and the antibody are kept rigid. Unlike the work of other authors, our algorithm does not attempt to explicitly maximize surface contact, but minimizes the energy computed using coarse-grained pair potentials. The final refinement of our best solutions using all-atom OPLS potentials (Jorgensen and Tirado-Rives8) consistently yields the native conformation as the preferred solution for three different antibodies. We find that the use of an exponential distance-dependent dielectric function is an improvement over the more commonly used linear form. PMID- 8460114 TI - From independent modules to molten globules: observations on the nature of protein folding intermediates. PMID- 8460115 TI - Adding neurons to the adult mammalian brain. PMID- 8460116 TI - Fleeting opportunities. PMID- 8460117 TI - Guanidine hydrochloride stabilization of a partially unfolded intermediate during the reversible denaturation of protein disulfide isomerase. AB - The reversible denaturation of protein disulfide isomerase proceeds through intermediates that are stabilized by interaction with guanidine hydrochloride. At pH 7.5, the equilibrium denaturation by urea is completely reversible and the transition can be reasonably well-described by a two-state model involving only native and denatured forms. In comparison, the equilibrium denaturation by guanidine hydrochloride occurs in two distinct steps. In the presence of a low constant amount of guanidine hydrochloride (0.5-1.4 M), urea denaturation also becomes biphasic, suggesting the accumulation of an intermediate species that is stabilized by specific interaction with guanidine hydrochloride but not by high concentrations of other salts or other denaturants. PMID- 8460119 TI - Atomic force microscopy of long DNA: imaging in air and under water. AB - We have obtained striking atomic force microscopy images of the intact lambda bacteriophage genome and of several lambda restriction fragments both in air and under water. The DNA is unstained and the images are stable under continuous scanning for up to 30 min. Measured contour lengths of fully imaged restriction fragments and intact lambda DNA are accurate to within a few percent. The key to this development is the use of a process for binding unmodified double-stranded DNA to chemically treated mica surfaces. This procedure leads to strong DNA attachment and yields high-quality images that are stable under repeated scanning, even with the sample submerged in water. This allows normal hydration conditions to be maintained during scanning and in addition leads to a general improvement of image quality. Both the lateral resolution and the contrast increase by a factor of approximately 3 under water. PMID- 8460118 TI - Charge-reversion mutagenesis of Dictyostelium actin to map the surface recognized by myosin during ATP-driven sliding motion. AB - Amino acid residues D24/D25, E99/E100, E360/E361, and D363/E364 in subdomain 1 of Dictyostelium actin were replaced with histidine residues by site-directed mutagenesis. Mutant actins were expressed in Dictyostelium cells and purified to homogeneity. The sliding movement of mutant actin filaments on heavy meromyosin attached to a glass surface was measured to assess the effect of the mutation on the motility of actin. For two C-terminal mutants, force generated by a single actin filament and myosin was also measured. These measurements indicated that both D24/D25 and E99/E100 are involved in ATP-driven sliding, whereas E360/E361/D363/E364 are not essential for ATP-driven sliding and force generation. PMID- 8460120 TI - Identification of a region of beta 2-glycoprotein I critical for lipid binding and anti-cardiolipin antibody cofactor activity. AB - beta 2-Glycoprotein I (beta 2-GPI), a phospholipid-binding plasma protein, is an absolute requirement (cofactor) for the binding of autoimmune-type anti cardiolipin (aCL) antibodies to cardiolipin (CL). The nature of this cofactor activity and the specific regions of the molecule involved have not yet been determined. We have identified a preparation of beta 2-GPI that lacks aCL antibody cofactor activity. Analysis of the structural differences between the active and inactive forms enabled identification of the region of beta 2-GPI critically important for aCL cofactor activity. The active form of beta 2-GPI bound CL and displayed cofactor activity down to 1 microgram/ml. The inactive form failed to bind CL and possessed no cofactor activity even at concentrations up to 94 micrograms/ml, indicating that the ability of beta 2-GPI to bind lipids is an absolute requirement for aCL cofactor activity. Both forms possessed identical N-terminal sequences and were recognized as essentially immunoreactively identical by polyclonal antisera to beta 2-GPI. However, the inactive form has undergone proteolytic cleavage and exists primarily as a "clipped" molecule, the polypeptide chain being cleaved between Lys-317 and Thr 318 (a potential thrombin cleavage site), with the two cleaved segments linked as a disulfide-bonded complex. This indicates that the C-terminal region is critically important for beta 2-GPI to bind lipid and for aCL cofactor activity. The clipped form of beta 2-GPI would not be suitable for use as aCL cofactor and its use may have led some investigators to conclude incorrectly that beta 2-GPI does not interact with aCL antibodies. PMID- 8460121 TI - A method for evaluation of activity of antagonistic analogs of growth hormone releasing hormone in a superfusion system. AB - Antagonistic analogs of growth hormone-releasing hormone (GHRH) are being synthesized in our laboratory for various clinical applications, including treatment of certain endocrine disorders and insulin-like growth factor I dependent tumors. To evaluate the endocrine effect of these GHRH antagonists, a sensitive dynamic in vitro system has been developed. The concentration causing 50% inhibition (IC50) of the standard GHRH antagonist human [N-Ac-Tyr1,D Arg2]GHRH-(1-29)-NH2 is 4.5 x 10(-8) M in our dispersed pituitary cell superfusion system. This value is 11 times less than that measured in earlier static pituitary cell cultures. This reliable dynamic system is simple, fast, and inexpensive and not only makes it possible to obtain quantitative data on the inhibitory capacity of the antagonists but also provides information about the intrinsic GHRH activity of the analog. The dynamic interactions of the GHRH antagonist, the GHRH receptors, and GH release can also be evaluated by this superfusion system. The pulsatile GH release induced by 10(-9) M human GHRH-(1 29)-NH2 was inhibited by two modes of application, preincubation and simultaneous administration of the GHRH antagonist (10(-9) to 10(-6) M). The reduction in GHRH stimulated GH response was more pronounced when the cells were preincubated with the antagonist prior to GHRH infusion than for simultaneous application. The inhibitory effect of the antagonist was dose-dependent, temporary, and of the competitive type. GH release induced by nonspecific stimulus (100 mM potassium chloride) was not influenced by the GHRH antagonist. This sensitive dynamic in vitro system appears to be a suitable method for screening the biological activity of various GHRH antagonists and eliminates the drawbacks of static pituitary cell culture. PMID- 8460122 TI - Suppression of apoptosis in a cytotoxic T-cell line by interleukin 2-mediated gene transcription and deregulated expression of the protooncogene bcl-2. AB - Absence of interleukin 2 (IL-2) from IL-2-dependent cells, such as the cytotoxic T-cell line CTLL2, causes DNA fragmentation and programmed cell death (apoptosis). We found that, upon initiation, DNA degradation proceeds rapidly. IL 2-deprived CTLL2 cells can be rescued from apoptosis by the addition of IL-2 2 h prior to the onset of detectable DNA breakdown. Addition of inhibitors of transcription with IL-2 abolished the IL-2-mediated rescue of CTLL2 cells. Thus it appears that IL-2-mediated gene transcription is necessary for survival. Deregulated expression of a protooncogene, bcl-2, inhibits apoptosis of cells dependent on other hematopoietic growth factors. To determine whether bcl-2 was active in CTLL2 cells, we transfected CTLL2 cells with a plasmid containing bcl-2 cDNA expressed under the metallothionein promoter and observed prolonged survival of the transfected cells upon IL-2 deprivation. Cell growth, however, was arrested in the G0/G1 or G2/M phases of the cell cycle. The prolonged survival of bcl-2 transfectants allowed the analysis of endogenous bcl-2 mRNA levels by Northern blot analysis. The expression of endogenous bcl-2 was down-regulated within 8 h of IL-2 withdrawal and was not detected after 3 days. Addition of IL-2 induced endogenous bcl-2 expression within 8 h. Full recovery of bcl-2 expression was achieved by 24 h after IL-2 addition. We conclude that the survival of death prone CTLL2 cells may be viewed as IL-2-dependent suppression of suicide, probably by the IL-2-induced expression of the cellular bcl-2 gene. PMID- 8460123 TI - Different AIDS incubation periods and their impacts on reconstructing human immunodeficiency virus epidemics and projecting AIDS incidence. AB - The objective of this study was to investigate heterogeneity in incubation distributions in different cohorts and to assess the sensitivity of back calculated infection rates to different assumptions about incubation times from human immunodeficiency virus (HIV) infection to AIDS diagnosis. Incubation distributions were estimated by using data from three different cohort studies. These and one other published incubation model were used as inputs for a back calculation procedure that reconstructed smooth HIV-infection rates from AIDS incidence among adults in the United States, allowing for changes over time in incubation. Incubation estimates from the different cohorts differed substantially. The cumulative HIV incidence estimates that result from using the different incubations are very different, but the back-calculated models all produce good fits to the observed diagnosis counts. We conclude that systematic differences in incubation times of different groups add substantially to the uncertainty inherent in using the back-calculation method to reconstruct HIV epidemics and project future numbers of AIDS cases. PMID- 8460124 TI - Dynamic and distributed properties of many-neuron ensembles in the ventral posterior medial thalamus of awake rats. AB - The traditional view that the map of the face in the ventral posterior medial thalamus (VPM) is static and highly discrete was derived largely from qualitative studies that reported only small, robust, and nonoverlapping receptive fields (RFs). Here, by using more quantitative techniques, we have provided evidence for an alternative hypothesis: the RFs in the VPM are large and overlapping and tend to shift as a function of post-stimulus time. These results were obtained through simultaneous recordings of up to 23 single neurons across the whisker representation in the VPM of rats. Under both awake and anesthetized conditions, these neurons responded robustly at short (4-6 ms) and/or long (15-25 ms) latencies to discrete vibromechanical stimulation of single facial whiskers. Computer graphics were used to construct three-dimensional plots depicting the magnitudes of neuronal responses to stimulation of each of several whiskers as a function of post-stimulus time. These "spatiotemporal RFs" demonstrated that (i) the RFs of VPM neurons are quite large, covering up to 20 whiskers and (ii) the spatial locations of these RFs may shift dramatically over the first 35 ms of post-stimulus time, especially from the caudal-most to the rostral-most whiskers on the face. These results suggest that the VPM contains a dynamic and distributed representation of the face, in which stimulus information is coded in both spatial and temporal domains. PMID- 8460125 TI - Ciliary neurotrophic factor prevents retrograde neuronal death in the adult central nervous system. AB - The neurocytokine ciliary neurotrophic factor (CNTF) was described originally as an activity that supports the survival of neurons of the chicken ciliary ganglia in vitro. The widespread expression of CNTF and its principal binding protein, CNTF receptor alpha, in the central and peripheral nervous systems suggests a broader trophic role for this peptide. In the present study, we report that CNTF prevents axotomy-induced cell death of neurons in the anteroventral and anterodorsal thalamic nuclei of the adult rat. Using the polymerase chain reaction, we also demonstrate the presence of CNTF and CNTF receptor alpha mRNA in these same thalamic nuclei. The coincidence of CNTF and its receptor in a population of neurons responding to the factor suggests a paracrine function for CNTF. The present findings establish that CNTF has significant effects on neurons of the central nervous system in vivo and demonstrate that neurocytokines can prevent cell death in the adult central nervous system. PMID- 8460126 TI - A dual mechanosensory and chemosensory neuron in Caenorhabditis elegans. AB - After light touch to its nose, the nematode Caenorhabditis elegans halts forward locomotion and initiates backing. Here we show that three classes of neurons (ASH, FLP, and OLQ) sense touch to the nose and hence are required for this avoidance response. ASH, FLP, and OLQ have sensory endings that contain axonemal cilia. Mutant animals that have defective ciliated sensory endings as well as laser-operated animals that lack ASH, FLP, and OLQ fail to respond to touch to the nose. Together with the previous work of others, these results demonstrate that C. elegans has at least five morphologically distinct classes of mechanosensory neurons. Interestingly, the ASH neuron also acts as a chemosensory neuron; it mediates the avoidance of noxious chemicals. Since ASH possesses both chemosensory and mechanosensory modalities, this neuron might be functionally analogous to vertebrate nociceptors, which mediate the sensation of pain. PMID- 8460127 TI - Polymerization of murine macrophage inflammatory protein 1 alpha inactivates its myelosuppressive effects in vitro: the active form is a monomer. AB - Macrophage inflammatory protein (MIP) 1 alpha has myelosuppressive and myeloprotective activity. That MIP-1 alpha polymerizes is known; this phenomenon was evaluated in terms of myelosuppression by assessing the effects of recombinant murine MIP-1 alpha on colony formation of murine and human myeloid progenitor cells in vitro. The following results are reported: (i) Polymerization is diluent- and concentration-dependent. (ii) Monomeric MIP-1 alpha is the active suppressive form for myeloid progenitor cells in vitro. (iii) Polymerized MIP-1 alpha is inactive and does not interfere with suppression by monomeric MIP-1 alpha. (iv) MIP-1 alpha has approximately 1000-fold higher specific activity than has been reported, but its effects are still specific for immature subsets of myeloid progenitors. (v) Suppression is initiated during the DNA-synthesis phase of the cell cycle. We conclude that polymerization of MIP-1 alpha might be a control mechanism that limits the myelosuppressive effects of monomeric MIP-1 alpha. PMID- 8460128 TI - Chicken neuronal acetylcholine receptor alpha 2-subunit gene exhibits neuron specific expression in the brain and spinal cord of transgenic mice. AB - Transgenic mice carrying the complete structural gene of the alpha 2 subunit of the chicken neuronal nicotinic acetylcholine receptor (nAChR) and 7 kilobase pairs (kbp) of 5' upstream and 3 kbp of 3' downstream sequences have been generated. The transgene was stably integrated in transgenic lines and transmitted to their progeny. Avian transgene expression was predominant in the central nervous system as detected by specific alpha 2-subunit cDNA amplification. Moreover, in at least two independent mouse lines, its expression appeared to be neuron-specific and reproducibly restricted to subregions in the brain and spinal cord, as revealed by in situ hybridization histochemistry. Most cranial motor nuclei were positive, and several of the alpha 2-subunit transgene expressing structures corresponded to cholinergic areas in rodents. This study reveals that regulatory mechanisms giving rise to neuronal-specific gene expression have been conserved at least in part between birds and mammals. PMID- 8460129 TI - Comparative reproductive success of communally breeding burying beetles as assessed by PCR with randomly amplified polymorphic DNA. AB - To understand the evolution of alternative reproductive strategies such as communal breeding, it is important to recognize the options open to individuals and to evaluate their consequences. The relative reproductive success of individuals taking each option is one of the most important of these consequences. Burying beetles, Nicrophorus, are an excellent model system for the investigation of reproductive cooperation because they can breed in pairs or communally and provide extensive parental care. In this study, we examine the relationship of the duration of care and the reproductive success of each potentially communally breeding adult. Ten experimental broods reared on mouse carcasses were buried by two males and two females. Using PCR with single short primers that randomly amplify polymorphic DNA, we determined the maternity and paternity of 98.2% and 99.5% of the offspring (n = 217), respectively. In 70% of the broods, both females produced larvae, and in 70%, both males inseminated one or both females. The male and female providing longer care, usually the larger of each sex, were the mother and father of most larvae (50-100%). PMID- 8460130 TI - Use of a zinc-finger consensus sequence framework and specificity rules to design specific DNA binding proteins. AB - We have designed three zinc-finger proteins with different DNA binding specificities. The design strategy combines a consensus zinc-finger framework sequence with previously characterized recognition regions such that the specificity of each protein is predictable. The first protein consists of three identical zinc fingers, each of which was expected to recognize the subsite GCG. This protein binds specifically to the sequence 5'-GCG-GCG-GCG-3' with a dissociation constant of approximately 11 microM. The second protein has three zinc fingers with different predicted preferred subsites. This protein binds to the predicted recognition site 5'-GGG-GCG-GCT-3' with a dissociation constant of 2 nM. Furthermore, selection experiments indicate that this is the optimal binding site. A permuted version of the second protein was also constructed and shown to preferentially recognize the corresponding permuted site 5'-GGG-GCT-GCG 3' over the non-permuted site. These results indicate that earlier observations on the specificity of zinc fingers can be extended to generalized zinc-finger structures and realize the use of zinc fingers for the design of site-specific DNA binding proteins. This consensus-based design system provides a useful model system with which to study details of zinc-finger-DNA specificity. PMID- 8460131 TI - Metal-binding site in a class I tRNA synthetase localized to a cysteine cluster inserted into nucleotide-binding fold. AB - The 10 class I aminoacyl-tRNA synthetases share a common N-terminal nucleotide binding fold. Idiosyncratic polypeptide insertions into this fold introduce residues important for activity, including those that interact with the tRNA acceptor helix. The class I Escherichia coli methionyl-tRNA synthetase (L methionine:tRNA(Met) ligase, EC 6.1.1.10), a 676-amino acid homodimer, was shown previously by others to contain zinc and to have an activity dependent on its presence. We show here by atomic absorption spectroscopy and zinc titrations the presence of 1 mol of zinc per polypeptide. Replacement of zinc with cobalt yields an active enzyme with a visible absorption spectrum characteristic of tetrahedral coordination to sulfur ligands and an intense metal-to-sulfur charge-transfer band at 340 nm. Mapping of the metal-binding site by zinc blotting of recombinant and proteolytic fragments localized the site to a polypeptide insertion between two strands and a beta-sheet in the N-terminal nucleotide-binding fold that contains the catalytic site. Beginning at Cys-145, this insertion contains a Cys Xaa2-Cys-Xaa9-Cys-Xaa2-Cys motif. Site-directed substitution of these cysteines with serines yielded proteins that were stable but generally devoid of activity. With this result there is now at least one example of a class I and of a class II E. coli tRNA synthetase with a metal-binding domain important for activity inserted into the catalytic domain. PMID- 8460132 TI - Activity of purified NIFA, a transcriptional activator of nitrogen fixation genes. AB - The NIFA protein activates transcription of nitrogen fixation (nif) operons by the sigma 54-holoenzyme form of RNA polymerase. We purified active NIFA from Klebsiella pneumoniae in the form of a maltose-binding protein (MBP)-NIFA fusion; proteolytic release of MBP yielded inactive and insoluble NIFA. MBP-NIFA activated transcription from the nifHDK promoter in a purified transcription system. Like the related transcriptional activator NTRC, MBP-NIFA catalyzed the ATP-dependent isomerization of closed complexes between sigma 54-holoenzyme and a promoter to open complexes. MBP-NIFA had a broader nucleotide specificity than NTRC, being able to utilize pyrimidine in addition to purine nucleoside triphosphates. Both MBP-NIFA and a purified C-terminal fragment of NIFA bound to the upstream activation sequence for the nifHDK promoter, as assessed by DNAse I footprinting. When assays were performed at 37 degrees C instead of the usual 30 degrees C, transcriptional activation, open complex formation, and DNA binding by MBP-NIFA were all abolished, consistent with the known heat lability of NIFA. However, the purified C-terminal fragment of NIFA still bound the upstream activation sequence at 37 degrees C, indicating that the function of the helix turn-helix DNA-binding motif is not inherently heat-labile. PMID- 8460133 TI - Spinach thioredoxin m inhibits DNA synthesis in fertilized Xenopus eggs. AB - A role for thioredoxin in metazoan DNA synthesis has been assessed by injecting rapidly dividing Xenopus eggs with purified heterologous thioredoxins, which might act as inhibitors if they were to replace resident thioredoxins in some but not all reaction steps. Of 10 tested proteins, spinach chloroplast thioredoxin m is the most potent inhibitor. Eggs cleave and produce cells lacking nuclei. DNA synthesis is severely reduced. Development arrests before gastrulation. In egg extracts, thioredoxin m inhibits incorporation of radioactive dCTP into DNA of sperm nuclei and M13 phage. Inhibition exceeds 90% when thioredoxin m and M13 DNA are preincubated together. The data support the interpretation that thioredoxins normally participate in initiation of metazoan DNA synthesis. PMID- 8460135 TI - Pathology of inhalational anthrax in 42 cases from the Sverdlovsk outbreak of 1979. AB - A large epidemic of anthrax that occurred in Sverdlovsk (now Ekaterinburg), Russia, in 1979 resulted in the deaths of many persons. A series of 42 necropsies, representing a majority of the fatalities from this outbreak, consistently revealed pathologic lesions diagnostic of inhalational anthrax, namely hemorrhagic necrosis of the thoracic lymph nodes in the lymphatic drainage of the lungs and hemorrhagic mediastinitis. Bacillus anthracis was recovered in bacterial cultures of 20 cases, and organisms were detected microscopically in the infected tissues of nearly all of the cases. A novel observation was primary focal hemorrhagic necrotizing pneumonia at the apparent portal of entry in 11 cases. Mesenteric lymphadenitis occurred in only 9 cases. This remarkably large series demonstrated the full range of effects of anthrax bacteremia and toxemia (edema especially adjacent to sites of extensive infection and pleural effusions) and hematogenously disseminated infection [hemorrhagic meningitis (21 cases) and multiple gastrointestinal submucosal hemorrhagic lesions (39 cases)]. PMID- 8460134 TI - Identification of Ras farnesyltransferase inhibitors by microbial screening. AB - A microbial screen using a yeast strain with conditional deficiency in the GPA1 gene was carried out to search for inhibitors of protein farnesyltransferase (PFT). A strain of Streptomyces was found to produce active compounds named UCF1 A, UCF1-B, and UCF1-C. Structural determination of these compounds revealed that UCF1-C is identical to the known antibiotic, manumycin, whereas UCF1-A and UCF1-B are structurally related to manumycin. All three UCF1 compounds suppress the lethality of gpa1 disruption, with UCF1-C exhibiting the strongest activity. UCF1 inhibits yeast as well as rat brain PFT. Fifty percent inhibition of yeast PFT activity is observed with 5 microM UCF1-C. Kinetic analyses of the inhibition suggest that UCF1-C acts as a competitive inhibitor of PFT with respect to farnesyl pyrophosphate, exhibiting a Ki of 1.2 microM, whereas the same compound appears to act as a noncompetitive inhibitor of PFT with respect to the farnesyl acceptor, the Ras protein. UCF1-C shows significant activity to inhibit the growth of Ki-ras-transformed fibrosarcoma, raising the possibility of its use as an antitumor drug. PMID- 8460136 TI - Identification of the promoter region of human interleukin 1 type I receptor gene: multiple initiation sites, high G+C content, and constitutive expression. AB - To better understand the role of interleukin 1 (IL-1) and its receptor in disease, we have isolated a genomic clone of the human IL-1 type I receptor and have identified the promoter region. There are multiple transcriptional initiation sites as demonstrated by primer extension. DNA sequence analysis shows that the promoter region contains neither a TATA nor a CAAT box; however, the 5' upstream regulatory elements contain two AP-1-like binding sites. The internal regulatory sequences found immediately downstream to the 5' transcriptional start site contain four Sp1 binding domains and have a high G+C content of 75%. This portion of the 5' untranslated region of the mRNA can form stable secondary structure as predicted by computer modeling. Base pairs -4 to + 10 share striking resemblance to an initiator sequence that directs basal expression of certain TATA-less genes-e.g., terminal deoxynucleotidyltransferase in lymphocytes. The IL 1 receptor promoter directs basal expression of chloramphenicol acetyltransferase in transiently transfected cells. Overall, the promoter of the IL-1 type I receptor gene resembles that of constitutively expressed genes that have housekeeping- and/or growth-related functions. The constitutive nature of the promoter may account for this gene being expressed at low levels in diverse cell types. Our finding sheds more understanding into the mechanisms governing the regulation of the IL-1 receptor in health and disease. PMID- 8460138 TI - From elongator tRNA to initiator tRNA. AB - We show that the two most important properties needed for a tRNA to function in initiation in Escherichia coli are its ability to be formylated and its ability to bind to the ribosomal P site. This conclusion is based on conversion of two different elongator tRNAs to ones that can act as initiators in E. coli. We transplanted the features unique to E. coli and eubacterial initiator tRNAs to E. coli elongator methionine tRNA (tRNA(Met)) along with an anticodon sequence change and analyzed their activities in initiation in E. coli. Introduction of a C1.A72 mismatch at the end of the acceptor stem of tRNA(Met), which generates the minimal features necessary for formylation, produces a tRNA with very low activity in initiation. Subsequent introduction of three consecutive G.C base pairs at the bottom of the anticodon stem, which is necessary for ribosomal P site binding, produces a tRNA with significant activity in initiation. Furthermore, introduction of the features necessary for formylation and for ribosomal P site binding into E. coli elongator glutamine tRNA produces a tRNA that initiates protein synthesis in E. coli. PMID- 8460137 TI - Constitutive transcription of the osteocalcin gene in osteosarcoma cells is reflected by altered protein-DNA interactions at promoter regulatory elements. AB - The bone-specific osteocalcin (OC) gene is transcribed only after completion of proliferation in normal diploid calvarial-derived osteoblasts during extracellular matrix mineralization. In contrast, the OC gene is expressed constitutively in both proliferating and nonproliferating ROS 17/2.8 osteosarcoma cells. To address molecular mechanisms associated with these tumor-related modifications in transcriptional control, we examined sequence-specific interactions of transactivation factors at key basal and hormone-responsive elements in the OC gene promoter. In ROS 17/2.8 cells compared to normal diploid osteoblasts, the absence of a stringent requirement for cessation of proliferation to support both induction of OC transcription and steroid hormone mediated transcriptional modulation is reflected by modifications in transcription factor binding at (i) the two primary basal regulatory elements, the OC box (which contains a CCAAT motif as a central core) and the TATA/glucocorticoid-responsive element domain, and (ii) the vitamin D-responsive element. Particularly striking are two forms of the vitamin D receptor complex that are present in proliferating osteoblasts and osteosarcoma cells. Both forms of the complex are sensitive to vitamin D receptor antibody and retinoic X receptor antibody. After the down-regulation of proliferation, only the lower molecular weight complex is found in normal diploid osteoblasts. Both forms of the complex are present in nonproliferating ROS 17/2.8 cells with increased representation of the complex exhibiting reduced electrophoretic mobility that is phosphorylation-dependent. PMID- 8460139 TI - Induction of manganese-containing superoxide dismutase in anaerobic Escherichia coli by diamide and 1,10-phenanthroline: sites of transcriptional regulation. AB - Transcriptional regulation of the sodA gene, a member of the soxRS regulon encoding the manganese-containing superoxide dismutase (MnSOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) of Escherichia coli, was examined in a variety of regulatory mutants. Diamide, an oxidant that causes the anaerobic biosynthesis of the MnSOD polypeptide and also facilitates insertion of manganese at the active site, was found to anaerobically induce MnSOD in both soxRS and fur arcA fnr strains. Metal chelating agents also caused anaerobic induction of MnSOD in a fur arcA fnr triple mutant; however, this induction of MnSOD and of glucose-6-phosphate dehydrogenase (G6PD) by 1,10-phenanthroline was dependent on an intact soxRS locus. A strain of E. coli bearing a fusion of the soxS promoter to lacZ was used to demonstrate that both diamide and 1,10 phenanthroline caused anaerobic activation of soxS transcription. These results indicate that (i) both diamide and 1,10-phenanthroline induce the soxRS regulon anaerobically by stimulation of soxS transcription; (ii) diamide, but not metal chelators, also induces MnSOD biosynthesis by a soxRS-independent mechanism, perhaps mediated by effects on fur, arcA, or fnr-mediated repression of sodA; and (iii) the soxRS locus contains a metal-binding component and is responsive to the redox status of the cell. PMID- 8460140 TI - Increased ribosomal accuracy increases a programmed translational frameshift in Escherichia coli. AB - We have tested the effect of increased ribosomal fidelity on a modified version of the programmed release factor 2 (RF2) translational frameshift. In the constructs tested, the original UGA codon at the site of the shift was replaced by either of two sense codons, UGG (tryptophan), which allows a frameshift of approximately 13%, or CUG (leucine), which allows a frameshift of only approximately 2%. We confirmed the results of Curran and Yarus [Curran, J. F. & Yarus, M. (1989) J. Mol. Biol. 209, 65-77] in a wild-type ribosomal host, including a reduction of the UGG shift following induction of tRNA(Trp) from a plasmid copy of the tRNA gene. But to our surprise, in a hyperaccurate streptomycin pseudo-dependent host, the UGG frameshift increased to more than 50%. When we added a tRNA(Trp) plasmid to these cells, induction of the tRNA(Trp) gene reduced the shift back to approximately 7%. Messenger RNA levels did not vary greatly under these different induced conditions. Other increased accuracy alleles also showed increased frameshifting with UGG at the frameshift site. All increased accuracy alleles led to slower translation rates, and there appeared to be a proportionality between the extent of reduction of synthesis for the in frame reporter and the extent of UGG frameshift for the out-of-frame reporter. There were little effects of increased accuracy on the lower level CUG frameshift. However, over-production of the cognate tRNA(1Leu) dramatically reduced even this lower level of shift, despite the fact that tRNA(1Leu) is already the most abundant isoacceptor in Escherichia coli. These results can be rationalized by following the hypothesis of Curran and Yarus as follows: with wild-type ribosomes, limited availability of tRNA(Trp) (about 1% of total tRNA) facilitates a pause at the UGG codon (due to the vacant A site), allowing increased opportunity for ribosome realignment. Excess tRNA(Trp) reduces the time the A site is vacant and thus reduces the frameshift. The slower hyperaccurate ribosomes increase the pause time and thus increase the opportunity for shifting, a process again reversed by increasing the in-frame cognate tRNA(Trp). These data provide strong support for a model in which the extent of ribosome pause time at a programmed frameshift site is a major determinant in the efficiency of the frameshift and in which tRNA availability can be a major influence on this process. PMID- 8460141 TI - The eukaryotic host factor that activates exoenzyme S of Pseudomonas aeruginosa is a member of the 14-3-3 protein family. AB - Exoenzyme S (ExoS), which has been implicated as a virulence factor of Pseudomonas aeruginosa, catalyzes transfer of the ADP-ribose moiety of NAD+ to many eukaryotic cellular proteins. Its preferred substrates include Ras and several other 21- to 25-kDa GTP-binding proteins. ExoS absolutely requires a ubiquitous eukaryotic protein factor, termed FAS (factor activating ExoS), for enzymatic activity. Here we describe the cloning and expression of a gene encoding FAS from a bovine brain cDNA library and demonstrate that purified recombinant FAS produced in Escherichia coli activates ExoS in a defined cell free system. The deduced amino acid sequence of FAS shows that the protein (245 residues, calculated molecular mass 27,743 Da) belongs to a highly conserved, widely distributed eukaryotic protein family, collectively designated as 14-3-3 proteins. Various functions have been reported for members of the 14-3-3 family, including phospholipase A2 activity and regulation of tyrosine hydroxylase, tryptophan hydroxylase, and, possibly, protein kinase C activities. Identification of FAS as a 14-3-3 protein establishes an additional function for this family of proteins--the activation of an exogenous ADP-ribosyltransferase. Elucidation of the precise role of FAS in activating ExoS will contribute to understanding the molecular mechanisms by which P. aeruginosa causes disease. PMID- 8460142 TI - SpoIIAB is an anti-sigma factor that binds to and inhibits transcription by regulatory protein sigma F from Bacillus subtilis. AB - The sigma F factor is a regulatory protein that is responsible for directing gene expression in the forespore compartment of developing cells of the spore-forming soil bacterium Bacillus subtilis. The sigma F factor is encoded by the promoter distal member of sporulation operon spoIIA, which consists of cistrons called spoIIAA, spoIIAB, and spoIIAC. Genetic evidence indicates that the activity of sigma F is negatively regulated by the product (SpoIIAB) of the spoIIAB cistron. We now report that SpoIIAB is capable of binding to sigma F and inhibiting its capacity to direct transcription by core RNA polymerase from the promoter for a forespore-expressed gene. SpoIIAB is an anti-sigma factor that may be directly involved in the compartmentalization of sigma F-directed gene expression. PMID- 8460143 TI - Bacillus subtilis sigma B is regulated by a binding protein (RsbW) that blocks its association with core RNA polymerase. AB - sigma B is a secondary sigma factor of Bacillus subtilis. RNA polymerase containing sigma B transcribes a subset of genes that are expressed after heat shock or the onset of the stationary phase of growth. Three genes (rsbV, rsbW, and rsbX), cotranscribed with the sigma B structural gene (sigB), regulate sigma B-dependent gene expression. RsbW is the primary inhibitor of this system with the other gene products acting upstream of RsbW in the sigma B regulatory pathway. Evidence is now presented that RsbW inhibits sigma B-dependent transcription by binding to sigma B and blocking the formation of a sigma B containing RNA polymerase holoenzyme. Antibodies specific for either RsbW or sigma B will coprecipitate both proteins from crude cell extracts. This is not due to the presence of both proteins on RNA polymerase. Western blot analysis of B. subtilis extracts that had been fractionated by gel-filtration chromatography revealed a single peak of RsbW that did not coelute with RNA polymerase and two peaks of sigma B protein: one that eluted with RNA polymerase and a second that overlapped the fractions that contained RsbW. Reconstitution experiments were performed in which partially purified sigma B and RsbW were added to core RNA polymerase and tested for their ability to influence the transcription of a sigma B-dependent promoter (ctc) in vitro. RsbW efficiently blocked sigma B-dependent transcription but only if it was incubated with sigma B prior to the addition of the core enzyme. PMID- 8460144 TI - Ontogeny of anti-human immunodeficiency virus (HIV) antibody production in HIV-1 infected infants. AB - The early serologic response of infants to infection with human immunodeficiency virus type 1 (HIV-1) is normally obscured by the presence of transplacentally acquired maternal HIV antibody. By measuring HIV antibody produced in vitro by lymphocytes isolated from peripheral blood of infants and children of HIV-1 infected mothers, we have been able to study the natural acquisition of humoral immunity to perinatal HIV-1 infection. One hundred ninety-seven infants of HIV-1 infected women were studied prospectively and longitudinally from birth. In the neonatal period, infected infants produced only small amounts of HIV-specific IgG antibodies to a restricted number of antigens. The amount of immunoglobulin to HIV-1 and the number of HIV-1 antigens recognized increased with age. After 6 months of life 85% of infected infants made detectable antibody to two or more viral proteins. Antibody to gp160 appeared first and was the most frequently found at all ages, followed by antibody to the envelope proteins gp120 and gp41. The amount of HIV antibody produced correlated positively with the percentage of CD4+ T lymphocytes in peripheral blood. This assay provides a method of studying the immunogenicity of vaccines against HIV-1 in HIV-1-infected infants and of assessing the effect of early therapeutic interventions on the humoral response to HIV-1. PMID- 8460145 TI - Immunoglobulin heavy chain constant region determines the pathogenicity and the antigen-binding activity of rheumatoid factor. AB - An IgG3 monoclonal antibody, 6-19, derived from unmanipulated MRL/MpJ-lpr/lpr mice, exhibiting cryoglobulin and anti-IgG2a rheumatoid factor activities, induces skin leukocytoclastic vasculitis and glomerulonephritis when injected into normal mice. To determine the role of the gamma 3 heavy chain constant region in the generation of cryoglobulins and associated tissue lesions, we have established an IgG1 class switch variant, clone SS2F8, from the 6-19 hybridoma by sequential sublining. Here we report that the SS2F8 monoclonal antibody, which loses the cryoglobulin activity but retains the rheumatoid factor activity, fails to generate skin and glomerular lesions. The lack of pathogenicity of the IgG1 SS2F8 switch variant is not due to mutations in variable regions, since nucleotide sequence analysis shows no differences between both clones. In addition, we have observed that the IgG1 SS2F8 switch variant exhibits < 10% of the rheumatoid factor activity, as compared with the IgG3 6-19 monoclonal antibody, suggesting that the self-associating property of the gamma 3 isotype promotes antibody-binding activity. The present study indicates that the cryoglobulin activity associated with the gamma 3 isotype is critically involved in the pathogenicity of 6-19 anti-IgG2a rheumatoid factor monoclonal antibody and highlights the pathogenic relevance of autoantibodies of the IgG3 subclass in murine systemic lupus erythematosus. PMID- 8460146 TI - Structure of glycosomal glyceraldehyde-3-phosphate dehydrogenase from Trypanosoma brucei determined from Laue data. AB - The three-dimensional structure of glycosomal glyceraldehyde-3-phosphate dehydrogenase [D-glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating), EC 1.12.1.12] from the sleeping-sickness parasite Trypanosoma brucei was solved by molecular replacement at 3.2-A resolution with an x-ray data set collected by the Laue method. For data collection, three crystals were exposed to the polychromatic synchrotron x-ray beam for a total of 20.5 sec. The structure was solved by using the Bacillus stearothermophilus enzyme model [Skarzynski, T., Moody, P. C. E. & Wonacott, A. J. (1987) J. Mol. Biol. 193, 171 187] with a partial data set which was 37% complete. The crystals contain six subunits per asymmetric unit, which allowed us to overcome the absence of > 60% of the reflections by 6-fold density averaging. After molecular dynamics refinement, the current molecular model has an R factor of 17.6%. Comparing the structure of the trypanosome enzyme with that of the homologous human muscle enzyme, which was determined at 2.4-A resolution, reveals important structural differences in the NAD binding region. These are of great interest for the design of specific inhibitors of the parasite enzyme. PMID- 8460147 TI - Bordetella pertussis tracheal cytotoxin and other muramyl peptides: distinct structure-activity relationships for respiratory epithelial cytopathology. AB - Tracheal cytotoxin (TCT) is a disaccharide-tetrapeptide released by Bordetella pertussis, the causative agent of pertussis (whooping cough). We have previously determined the structure of TCT to be GlcNAc-1,6-anhydro-MurNAc-L-Ala-gamma-D-Glu meso-A2pm-D-Ala, where MurNAc = N-acetylmuramic acid and A2pm = diaminopimelic acid. Purified TCT reproduces the respiratory cytopathology observed during pertussis, including ciliostasis and extrusion of ciliated cells. We have tested structural analogs of TCT for their ability to reproduce native TCT toxicity in explanted hamster tracheal tissue and hamster trachea epithelial (HTE) cell cultures. Other investigators have evaluated many of these analogs, which are muramyl or desmuramyl peptides, for muramyl peptide activities such as immunopotentiation, induction of slow-wave sleep, and pyrogenicity. Four desmuramyl peptides were produced in our laboratory from B. pertussis peptidoglycan or by chemical synthesis, including unusual peptides containing alpha-aminopimelic acid in place of A2pm. Based on the relative ability of compounds to inhibit DNA synthesis in HTE cells, truncated analogs lacking A2pm entirely or lacking only the side-chain amine or carboxyl group of A2pm were less active than TCT by a factor of at least 1000. All active analogs included a native or near-native peptide moiety, independent of the presence, absence, or substitution of the sugar moiety. We conclude that the structural requirements for TCT toxicity differ considerably from those for most other muramyl peptide activities, in that the disaccharide moiety is irrelevant for toxicity and both the free amino and carboxyl groups of the A2pm side chain are required for activity. PMID- 8460148 TI - Passenger transgenes reveal intrinsic specificity of the antibody hypermutation mechanism: clustering, polarity, and specific hot spots. AB - We have analyzed somatic hypermutation in mice carrying an immunoglobulin kappa transgene in order to discriminate mutations that reflect the intrinsic specificity of the hypermutation mechanism from those highlighted by antigenic selection. We have immunized animals with three different immunogens. With one immunogen, the antigen-specific B cells express a transgenic kappa chain, which does not form part of the antibody; the transgene is a passenger free to accumulate unselected mutations. With the other two immunogens, the transgenic kappa chain constitutes the light chain of the expressed antibody. A comparison of the transgene mutations obtained under these different circumstances allows us to identify common features that we attribute to the intrinsic specificity of the hypermutation process. In particular, it yields only base substitutions and leads to hot spots occurring in individual positions (e.g., the second base of the Ser 31 codon). The mutations preferentially accumulate around the first complementarity-determining region. The process exhibits specific base substitution preferences with transitions being favored over transversions. We propose that these substitution preferences can be used to discriminate intrinsic from antigen-selected hot spots. We also note that hypermutation distinguishes between the coding and noncoding strands since pyrimidines (particularly thymidines) mutate less frequently than purines. PMID- 8460149 TI - Targeted modification of the apolipoprotein B gene results in hypobetalipoproteinemia and developmental abnormalities in mice. AB - Familial hypobetalipoproteinemia is an autosomal codominant disorder resulting in a dramatic reduction in plasma concentrations of apolipoprotein (apo) B, cholesterol, and beta-migrating lipoproteins. A benefit of hypobetalipoproteinemia is that mildly affected individuals may be protected from coronary vascular disease. We have used gene targeting to generate mice with a modified Apob allele. Mice containing this allele display all of the hallmarks of human hypobetalipoproteinemia: they produce a truncated apoB protein, apoB70, and have markedly decreased plasma concentrations of apoB, beta-lipoproteins, and total cholesterol. In addition, the mice manifest several characteristics that are occasionally observed in human hypobetalipoproteinemia, including reduced plasma triglyceride concentrations, fasting chylomicronemia, and reduced high density lipoprotein cholesterol. An unexpected finding is that the modified Apob allele is strongly associated with exencephalus and hydrocephalus. These mice should help increase our understanding of hypobetalipoproteinemia, atherogenesis, and the etiology of exencephalus and hydrocephalus. PMID- 8460150 TI - Long-term retention of learning-induced receptive-field plasticity in the auditory cortex. AB - Brief learning experience (classical conditioning) induces frequency-specific receptive-field (RF) plasticity in the auditory cortex, characterized as increased response to the frequency of the conditioned stimulus and decreased responses to most other frequencies, including the pretraining best frequency. This experiment asked (i) whether learning-induced RF plasticity, established in the waking state, can be expressed under general anesthesia and if so (ii) whether it exhibits long-term retention. Pure-tone-frequency RFs were obtained from adult guinea pigs under general anesthesia (sodium pentobarbital or ketamine) before and repeatedly after (1 hr-8 weeks) a 20- to 30-trial session of pairing a non-best-frequency tone with mild footshock. Conditioned-stimulus specific RF plasticity was expressed under both types of anesthesia and included shifts of the pretraining best frequency toward or even to the frequency of the conditioned stimulus. Moreover, this RF plasticity exhibits long-term retention, being evident 1-8 weeks after training. This satisfies a criterion for the long term storage of information in the auditory cortex. PMID- 8460151 TI - Inhibitors of human immunodeficiency virus integrase. AB - In an effort to further extend the number of targets for development of antiretroviral agents, we have used an in vitro integrase assay to investigate a variety of chemicals, including topoisomerase inhibitors, antimalarial agents, DNA binders, naphthoquinones, the flavone quercetin, and caffeic acid phenethyl ester as potential human immunodeficiency virus type 1 integrase inhibitors. Our results show that although several topoisomerase inhibitors--including doxorubicin, mitoxantrone, ellipticines, and quercetin--are potent integrase inhibitors, other topoisomerase inhibitors--such as amsacrine, etoposide, teniposide, and camptothecin--are inactive. Other intercalators, such as chloroquine and the bifunctional intercalator ditercalinium, are also active. However, DNA binding does not correlate closely with integrase inhibition. The intercalator 9-aminoacridine and the polyamine DNA minor-groove binders spermine, spermidine, and distamycin have no effect, whereas the non-DNA binders primaquine, 5,8-dihydroxy-1,4-naphthoquinone, and caffeic acid phenethyl ester inhibit the integrase. Caffeic acid phenethyl ester was the only compound that inhibited the integration step to a substantially greater degree than the initial cleavage step of the enzyme. A model of 5,8-dihydroxy-1,4-naphthoquinone interaction with the zinc finger region of the retroviral integrase protein is proposed. PMID- 8460152 TI - cDNA and protein sequence of polymorphic macaque albumins that differ in bilirubin binding. AB - The rhesus monkey, Macaca mulatta, exhibits a geographically restricted polymorphism of serum albumins Mac A and Mac B that is recognized by electrophoresis and is associated with a difference in bilirubin-binding parameters. To identify the basis of the polymorphism, the cDNA and protein sequences of serum albumin from M. mulatta were determined. Screening of a lambda gt11 rhesus liver cDNA library yielded a 1988-bp cDNA sequence that encodes the complete amino acid sequence of mature albumin, the entire propeptide, and part of the prepropeptide. Isoelectric focusing and amino-terminal protein sequencing of CNBr fragments of albumin from A/A and B/B homozygotes were performed, and the structural difference was localized to a CNBr fragment (MCB3) spanning residues 124-264. Sequence analysis of lysyl endopeptidase peptides of MCB3 established that Mac A albumin has a glutamine residue at position 188 while the Mac B albumin has a glutamic residue at the same position. PCR amplification, subcloning, and DNA sequence analysis of clones from A/A and B/B homozygotes confirmed the protein sequence data and the codon difference of CAA versus GAA, respectively. Comparison of macaque and human serum albumin shows a 93.5% identity at the amino acid level. In human serum albumin, Glu188 is located close to the IIA binding pocket for ligands, probably including bilirubin. Derivatives of coumarin compete more efficiently with bilirubin for binding sites on the Mac A albumin than on the Mac B albumin. In regions where coumarin-containing plants are important food resources, Mac B albumin may confer a selective advantage because bilirubin is less readily displaced from it. PMID- 8460153 TI - A mammalian DNA-binding protein that contains a chromodomain and an SNF2/SWI2 like helicase domain. AB - Two overlapping cDNAs that encode a 197-kDa sequence-selective DNA-binding protein were isolated from libraries derived from mouse lymphoid cell mRNA. In addition to a DNA-binding domain, the protein contains both a chromodomain, which occurs in proteins that are implicated in chromatin compaction, and an SNF2/SWI2 like helicase domain, which occurs in proteins that are believed to activate transcription by counteracting the repressive effects of chromatin structure. A Southern blot analysis indicated that this protein, which we have named CHD-1, for chromodomain-helicase-DNA-binding protein, is present in most, if not all, mammalian species. A Northern blot analysis revealed multiple CHD mRNA components that differed both qualitatively and quantitatively among various cell types. The various mRNAs, which are probably produced by alternative RNA processing, could conceivably encode tissue-specific and developmental stage-specific isoforms of the protein. Based on its interesting combination of features, we suspect that CHD-1 plays an important role in gene regulation. PMID- 8460154 TI - Inducible operation of the erythropoietin 3' enhancer in multiple cell lines: evidence for a widespread oxygen-sensing mechanism. AB - Adaptive responses to hypoxia occur in many biological systems. A well characterized example is the hypoxic induction of the synthesis of erythropoietin, a hormone which regulates erythropoiesis and hence blood oxygen content. The restricted expression of the erythropoietin gene in subsets of cells within kidney and liver has suggested that this specific oxygen-sensing mechanism is restricted to specialized cells in those organs. Using transient transfection of reporter genes coupled to a transcriptional enhancer lying 3' to the erythropoietin gene, we show that an oxygen-sensing system similar, or identical, to that controlling erythropoietin expression is wide-spread in mammalian cells. The extensive distribution of this sensing mechanism contrasts with the restricted expression of erythropoietin, suggesting that it mediates other adaptive responses to hypoxia. PMID- 8460155 TI - Resistance to human immunodeficiency virus 1 infection of SCID mice reconstituted with peripheral blood leukocytes from donors vaccinated with vaccinia gp160 and recombinant gp160. AB - SCID mice reconstituted with adult human peripheral blood leukocytes (hu-PBL-SCID mice) make antigen-specific human antibody responses following secondary immunization and can be infected with human immunodeficiency virus 1 (HIV-1), suggesting that they might prove useful for evaluating protective immunity to HIV 1 following vaccination of PBL donors. HIV-seronegative volunteers were immunized with vaccinia expressing HIV-1LAV-1/Bru 160-kDa envelope glycoprotein (vaccinia gp160) and subsequently given booster injections of recombinant gp160 protein (rgp160). Their PBLs were used at intervals of 4-72 weeks after booster injections to construct hu-PBL-SCID mice, which were then challenged with 10(2) 10(3) minimal animal infectious doses of highly homologous HIV-1IIIB. Control hu PBL-SCID mice were constructed from donors receiving vaccinia, alum, or hepatitis B vaccine. Protection against virus infection was defined as the absence of HIV-1 by culture and no detection of proviral genomes following PCR amplification. Control animals were highly susceptible to HIV infection. By contrast, hu-PBL SCID mice reconstituted with cells from three of four donors immunized with vaccinia gp160 and recently injected with rgp160 showed no evidence of HIV-1 infection by culture or PCR assays. With increasing time after rgp160 injection, the ability of vaccine-derived hu-PBL-SCID mice to resist HIV-1 infection diminished. These results demonstrate that a potentially protective human immune response was stimulated by this HIV gp160 immunization protocol and show the utility of the hu-PBL-SCID model in the rapid evaluation of candidate vaccines. PMID- 8460156 TI - Determination of the myosin step size from mechanical and kinetic data. AB - During muscle contraction, work is generated when a myosin cross-bridge attaches to an actin filament and exerts a force on it through some power-stroke distance, h. At the end of this power stroke, attached myosin heads are carried into regions where they exert a negative force on the actin filament (the drag stroke) and where they are released rapidly from actin by ATP binding. Although the length of the power stroke remains controversial, average distance traversed in the drag-stroke region can be determined when one knows both rate of cross-bridge dissociation and filament-sliding velocity. At maximum contraction velocity, the average force exerted in the drag stroke must balance that exerted in the power stroke. We discuss here a simple model of cross-bridge interaction that allows one to calculate the force exerted in the drag stroke and to relate this to the power-stroke distance h traversed by cross-bridges in the positive-force region. Both the rate at which myosin can be dissociated from actin and the velocity at which an actin filament can be translated have been measured for a series of myosin isozymes and for different substrates, producing a wide range of values for each. Nonetheless, we show here that the rate of myosin dissociation from actin correlates well with the velocity of filament sliding, providing support for the simple model presented and suggesting that the power stroke is approximately 10 nm in length. PMID- 8460157 TI - Callatostatins: neuropeptides from the blowfly Calliphora vomitoria with sequence homology to cockroach allatostatins. AB - Five neuropeptides with C-terminal amino acid sequence homology to cockroach allatostatins have been identified in the blowfly Calliphora vomitoria. Three have the same pentapeptide C-terminal amino acid sequence as allatostatin 1 of the cockroach Diploptera punctata. A hexadecapeptide designated callatostatin 1, isolated from thoracic ganglia, brains, and heads, has the sequence Asp-Pro-Leu Asn-Glu-Glu-Arg-Arg-Ala-Asn-Arg-Tyr-Gly-Phe-Gly-Leu-NH2. Callatostatins 2 and 3 have been isolated from heads and thoracic ganglia, respectively; they comprise the last 14 and 8 residues of callatostatin 1. Callatostatin 4, isolated from thoracic ganglia, has the sequence Xaa-Arg-Pro-Tyr-Ser-Phe-Gly-Leu-NH2, where Xaa is either Asp or Asn. This peptide, with a serine substitution for glycine at position 5, has a C-terminal pentapeptide sequence identical to that of allatostatins 3 and 4 of D. punctata. Callatostatin 5, with the sequence Gly-Pro Pro-Tyr-Asp-Phe-Gly-Met-NH2, was identified from whole flies. All five peptides inhibit juvenile hormone production by the corpora allata of D. punctata in vitro. Callatostatin 5 was the most potent allatostatin so far tested in this species, with maximum inhibition occurring at 1 nM. In contrast, none of the callatostatins or the allatostatins showed allatostatic activity in mature female C. vomitoria when tested at concentrations of 100 to 0.1 microM. In accordance with these results, immunoreactivity to an antiserum directed against the common C terminus of callatostatin 1 and allatostatin 1 was observed in the corpora allata of D. punctata but not in the corpus allatum of C. vomitoria, despite its presence in neurons of the brain. Neurons in the thoracic ganglion of C. vomitoria that are immunoreactive against this antiserum project to the hindgut, rectum, rectal papillae, and oviduct, suggestive of a function different from that of a true allatostatin. PMID- 8460158 TI - Expression of the KAL gene in multiple neuronal sites during chicken development. AB - The human KAL gene is responsible for the X chromosome-linked Kallmann syndrome. A partial cDNA sequence from the chicken KAL homologue was determined and used to study expression of the KAL gene, by in situ hybridization, during chicken development, from day 6 of incubation. The KAL gene is mainly expressed in neurons of the central nervous system during the second half of embryonic life. High levels of transcript were detected in mitral neurons of the olfactory bulbs, in striatal neurons, in Purkinje cells of the cerebellum, in retinal neurons, and in isolated neurons of the brainstem and spinal cord. No expression was observed in glial cells. A low level of expression was observed in some mesenchymal derivatives. In the adult, expression is maintained or increased in several neuronal populations, especially in optic tectum and striatum. A possible role for the KAL protein in synaptogenesis at these stages is discussed. These results in the chicken embryo help to elucidate the mechanisms of anosmia and gonadotropin-releasing hormone deficiency, which define Kallmann syndrome. In addition, most of the occasional symptoms described in Kallmann syndrome patients, such as cerebellar ataxia, abnormal ocular movements, abnormal spatial visual attention, mirror movements, and renal aplasia, could be ascribed to malfunction of areas that, in the chicken, express the KAL gene. PMID- 8460159 TI - The granulocyte-macrophage colony-stimulating factor/interleukin 3 locus is regulated by an inducible cyclosporin A-sensitive enhancer. AB - Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 3 (IL 3) are pleiotropic hemopoietic growth factors whose genes are closely linked and induced in T lymphocytes in a cyclosporin A (CsA)-sensitive fashion. Since we found that the human GM-CSF and IL-3 proximal promoters were not sufficient to account for the observed regulation of these genes, we mapped DNase I hypersensitive sites across the GM-CSF/IL-3 locus in the Jurkat human T-cell line to identify additional regulatory elements. We located an inducible DNase I hypersensitive site, 3 kb upstream of the GM-CSF gene, that functioned as a strong CsA-sensitive enhancer of both the GM-CSF and IL-3 promoters. Binding studies employing Jurkat cell nuclear extracts indicated that four sites within the enhancer associate with the inducible transcription factor AP1. Three of these AP1 elements lie within sequences that also associate with factors resembling the CsA-sensitive, T cell-specific transcription factor NFAT. We provide additional evidence suggesting that an AP1-like factor represents one of the components of NFAT. We propose that the intergenic enhancer described here is required for the correctly regulated activation of both GM-CSF and IL-3 gene expression in T cells and that it mediates the CsA sensitivity of the GM-CSF/IL-3 locus. PMID- 8460160 TI - Expression of a human acetylcholinesterase promoter-reporter construct in developing neuromuscular junctions of Xenopus embryos. AB - We have employed Xenopus embryos to express human acetylcholinesterase (AcChoEase; EC 3.1.1.7) in developing synapses. Transcription of AcChoEase mRNA was driven by a 2.2-kb sequence upstream from the initiator AUG in the ACHE gene encoding AcChoEase, with multiple potential sites for binding universal and tissue-specific transcription factors. These included clustered MyoD elements, E box, SP1, EGR1, AP-2, and the development-related GAGA motif. A DNA construct composed of this sequence linked to a 2.1-kb sequence encoding human AcChoEase was designated human AcChoEase promoter-reporter (HpACHE). HpACHE but none of its several 5'-truncated derivatives was transcriptionally active in developing Xenopus embryos. Furthermore, PCR analysis using chimeric PCR primers revealed usage of the same 1.5-kb intron and 74-bp exon within the HpACHE sequence in microinjected embryos and various human tissues. Cytochemical staining revealed conspicuous accumulation of overexpressed AcChoEase in neuromuscular junctions and within muscle fibers of apparently normal 2-day Xenopus embryos injected with HpACHE. The same reporter driven by the cytomegalovirus promoter was similarly efficient in directing the heterologous human enzyme toward neuromuscular junctions, attributing the evolutionary conservation of AcChoEase targeting to the coding sequence. Our findings demonstrate that a short DNA sequence is sufficient to promote the exogenous transcription and faithful splicing of human AcChoEase mRNA in developing Xenopus embryos and foreshadow their use for integrative studies of cholinergic signaling and synapse formation. PMID- 8460161 TI - Existence of an inactive pool of acetylcholinesterase in chicken brain. AB - We analyzed acetylcholinesterase (AcChoEase; EC 3.1.1.7) activity and AcChoEase immunoreactive protein in chicken brain by using five monoclonal antibodies raised against chicken AcChoEase. Four of them specifically recognized AcChoEase catalytic subunits in Western blots and one, C-131, recognized only enzymatically active AcChoEase. We observed considerable differences in the ratio of immunoreactive protein to catalytic activity in various fractions, indicating the existence of inactive AcChoEase protein. This inactive AcChoEase component was more abundant in a low-salt-soluble extract than in a subsequent detergent soluble extract. On the basis of the ratio between activity and immunoreactivity, we calculated that the inactive component represents about 30% of the total AcChoEase subunits in chicken brain. The immunoreactive AcChoEase protein sedimented in sucrose gradients like the active molecular forms; the G1 and G2 peaks contained inactive molecules, whereas the G4 peak appeared to contain only active AcChoEase. The bulk of inactive AcChoEase reacted with the organophosphate cholinesterase inhibitor O-ethyl S-[2 (diisopropylamino)ethyl]methylphosphonothioate (MTP) but was found to bind the active site affinity ligand N-methylacridinium poorly and was not recognized by the active-form-specific monoclonal antibody, C-131. In addition, most of this fraction is sensitive to endoglycosidase H and binds the lectin wheat germ agglutinin poorly, suggesting that it was not processed in the Golgi apparatus. From these observations, we propose that the active and inactive AcChoEase components are differently folded. PMID- 8460162 TI - Structural and functional differences between histone H1 sequence variants with differential intranuclear distribution. AB - The chromatin of most cell types contains several different sequence variants of histone H1. The functional role of this heterogeneity is not known. In the larval tissues of the midge, Chironomus thummi, there are H1 variants of two types. H1 II-1, H1 II-2, and H1 III-1 have similar amino acid sequences and appear uniformly distributed in polytene interphase chromosomes. The total number of gene copies per genome for this type of H1 histones is about 40 in C. th. thummi and 50-60 in C. th. piger. In contrast, histone H1 I-1 is encoded by a single copy gene in C. th. thummi and by two to four genes in C. th. piger. It has a divergent structure and is found only in a limited number of condensed chromosome sites. The N-terminal domain of H1 I-1 contains an insertion that is lacking in the other H1 variants and that is part of a variant-specific bipartite sequence Lys-Ala-Pro-Lys-Ala-Pro-Xaa10-Lys-Val-Ala in front of the conserved central domain. N-terminal peptides of H1 I-1 including this motif, in contrast to the homologous peptide from H1 II-1, competed with the drug Hoechst 33258 for binding to the minor groove of the DNA double helix. Repeats of the sequence Lys-Ala-Pro are also present at the same distance from the conserved central domain, in a single H1 variant of a nematode and of a green alga. The motif could interact with linker DNA in intranuclear targeting or packaging a condensed subtype of chromatin, or both. PMID- 8460163 TI - Stearoyl-acyl carrier protein delta 9 desaturase from Ricinus communis is a diiron-oxo protein. AB - A gene encoding stearoyl-acyl carrier protein delta 9 desaturase (EC 1.14.99.6) from castor was expressed in Escherichia coli. The purified catalytically active enzyme contained four atoms of iron per homodimer. The desaturase was studied in two oxidation states with Mossbauer spectroscopy in applied fields up to 6.0 T. These studies show conclusively that the oxidized enzyme contains two (identical) clusters consisting of a pair of antiferromagnetically coupled (J > 60 cm-1, H = JS1.S2) Fe3+ sites. The diferric cluster exhibited absorption bands from 300 to 355 nm; addition of azide elicited a charge transfer band at 450 nm. In the presence of dithionite, the clusters were reduced to the diferrous state. Addition of stearoyl-CoA and O2 returned the clusters to the diferric state. These properties are consistent with assigning the desaturase to the class of O2 activating proteins containing diiron-oxo clusters, most notably ribonucleotide reductase and methane monooxygenase hydroxylase. Comparison of the primary structures for these three catalytically diverse proteins revealed a conserved pair of the amino acid sequence -(Asp/Glu)-Glu-Xaa-Arg-His- separated by approximately 100 amino acids. Since each of these proteins can catalyze O2 dependent cleavage of unactivated C--H bonds, we propose that these amino acid sequences represent a biological motif used for the creation of reactive catalytic intermediates. Thus, eukaryotic fatty acid desaturation may proceed via enzymatic generation of a high-valent iron-oxo species derived from the diiron cluster. PMID- 8460165 TI - Dissociation of glucose-regulated protein Grp78 and Grp78-IgE Fc complexes by ATP. AB - Recent studies have shown that ATP can dissociate dimers of the glucose-regulated protein Grp78 to monomers. In the present study, we have used purified recombinant Grp78 from Escherichia coli to investigate this reaction in more detail. During the course of the Grp78 dimer-monomer conversion, a stable Grp78 monomer-ATP complex is formed. Upon removal of the ATP, the Grp78 dimer is reformed. ADP, nonhydrolyzable ATP analogues, and GTP do not effect the dissociation of Grp78 dimers. A cell line that overproduces IgE Fc has been used to examine the nature of the Grp78-IgE Fc complexes present and the effect of ATP on them. Grp78-IgE Fc complexes ranging from 100 kDa to 300 kDa were observed by sucrose gradient analysis, suggesting that aggregate forms of Grp78 may be present in some of these complexes. Treatment of the extracts with ATP resulted in release of a Grp78 monomer from the complex. These results suggest that the dissociation of Grp78 oligomers by ATP may be involved in the function of Grp78 in protein translocation through the endoplasmic reticulum. PMID- 8460164 TI - Mutation of Arg-115 of human class III alcohol dehydrogenase: a binding site required for formaldehyde dehydrogenase activity and fatty acid activation. AB - The origin of the fatty acid activation and formaldehyde dehydrogenase activity that distinguishes human class III alcohol dehydrogenase (alcohol:NAD+ oxidoreductase, EC 1.1.1.1) from all other alcohol dehydrogenases has been examined by site-directed mutagenesis of its Arg-115 residue. The Ala- and Asp 115 mutant proteins were expressed in Escherichia coli and purified by affinity chromatography and ion-exchange HPLC. The activities of the recombinant native and mutant enzymes toward ethanol are essentially identical, but mutagenesis greatly decreases the kcat/Km values for glutathione-dependent formaldehyde oxidation. The catalytic efficiency for the Asp variant is < 0.1% that of the unmutated enzyme, due to both a higher Km and a lower kcat value. As with the native enzyme, neither mutant can oxidize methanol, be saturated by ethanol, or be inhibited by 4-methylpyrazole; i.e., they retain these class III characteristics. In contrast, however, their activation by fatty acids, another characteristic unique to class III alcohol dehydrogenase, is markedly attenuated. The Ala mutant is activated only slightly, but the Asp mutant is not activated at all. The results strongly indicate that Arg-115 in class III alcohol dehydrogenase is a component of the binding site for activating fatty acids and is critical for the binding of S-hydroxymethylglutathione in glutathione dependent formaldehyde dehydrogenase activity. PMID- 8460166 TI - Analysis of banded human chromosomes and in situ hybridization patterns by scanning force microscopy. AB - Scanning force microscopy was used to analyze banded human chromosomes and in situ hybridization patterns of biotinylated DNA probes. In standard human GTG banded metaphase chromosome preparations (where GTG is G-banding with trypsin Giemsa), chromosomal morphology and banding patterns were well preserved during the scanning procedure. The smallest identifiable features were in the range of about 100 nm and are similar to the typical structures seen by electron microscopy. In addition, in situ hybridization of human DNA probes of known chromosomal localization was used to map specific hybridization signals. Imaging of the precipitated crystals at the hybridization site clearly demonstrates the superior resolution of scanning force microscopy compared to conventional microscopy. PMID- 8460167 TI - Chromosomal structure of Rhodobacter capsulatus strain SB1003: cosmid encyclopedia and high-resolution physical and genetic map. AB - A combination of cosmid genome walking and pulsed-field gel electrophoresis was used to construct a high-resolution physical and genetic map of the 3.8-megabase (Mb) genome of Rhodobacter capsulatus SB1003. The mapping was done by hybridization of pulsed-field gel blots and by grouping and further mapping of the cosmids and bacteriophages from genomic libraries. Cosmid clones formed two uninterrupted and ordered groups, one corresponding to the chromosome of R. capsulatus, the other to its 134-kb plasmid. Cos site end-labeling and partial EcoRV digestion of cosmids were used to construct a high-resolution EcoRV map of the genome. Overlapping of the cosmids was confirmed by the resemblance of the cosmid restriction maps and by direct end-to-end hybridization with SP6- and T7 specific transcripts. Twenty-three previously cloned genes and eight groups of repeated sequences, revealed in this work, were located in the ordered gene library and mapped with an accuracy of 1-10 kb. Blots of a minimal set of 192 cosmids, covering the chromosome and the plasmid with the known map position of each cosmid, give to R. capsulatus the same advantages that the Kohara phage panel gives to E. coli. PMID- 8460168 TI - Combinatorial autoantibodies to dihydrolipoamide acetyltransferase, the major autoantigen of primary biliary cirrhosis. AB - mRNA from a regional lymph node of a patient with primary biliary cirrhosis (PBC) was used to construct a combinatorial immunoglobulin library in the lambda phage vector system. Six human monoclonal IgG Fab clones (LC1-LC6) specific for the major autoantigen of PBC--dihydrolipoamide acetyltransferase, the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2)--were isolated, appearing at a frequency of 0.01% in the combinatorial immunoglobulin library. These Fab clones recognize human PDC-E2 with high affinity (Ka = 10(-7)-10(-9) M-1). Using both immunoblotting and ELISA, LC1-LC6 showed little cross-reactivity to any of the other autoantigens commonly recognized by PBC sera or to other antigens commonly recognized by PBC sera or to other antigens such as histone, calf thymus DNA, and bovine serum albumin. The Fab monoclonal antibodies show a typical anti mitochondrial staining pattern in HEp-2 cells but react strongly with the luminal aspect of biliary epithelial cells of patients with PBC. Our results demonstrate that a recombinant combinatorial immunoglobulin library can be used to isolate high-affinity Fabs against a specific autoantigen. Such reagents will facilitate the analysis of immunoglobulin gene structure, idiotype, and antigen-antibody interactions in autoimmune disease. PMID- 8460169 TI - Mutual regulation of the transcriptional activator NF-kappa B and its inhibitor, I kappa B-alpha. AB - The NK-kappa B transcription factor complex is sequestered in the cytoplasm by the inhibitory protein I kappa B-alpha (MAD-3). Various cellular stimuli relieve this inhibition by mechanisms largely unknown, leading to NF-kappa B nuclear localization and transactivation of its target genes. It is demonstrated here with human T lymphocytes and monocytes that different stimuli, including tumor necrosis factor alpha and phorbol 12-myristate 13-acetate, cause rapid degradation of I kappa B-alpha, with concomitant activation of NF-kappa B, followed by a dramatic increase in I kappa B-alpha mRNA and protein synthesis. Transfection studies reveal that the I kappa B-alpha mRNA and the encoded protein are potently induced by NF-kappa B and by homodimers of p65 and of c-Rel. We propose a model in which NF-kappa B and I kappa B-alpha mutually regulate each other in a cycle: saturating amounts of the inhibitory I kappa B-alpha protein are destroyed upon stimulation, allowing rapid activation of NF-kappa B. Subsequently, I kappa B-alpha mRNA and protein levels are quickly induced by the activated NF-kappa B. This resurgence of I kappa B-alpha protein acts to restore an equilibrium in which NF-kappa B is again inhibited. PMID- 8460170 TI - An intron within the 16S ribosomal RNA gene of the archaeon Pyrobaculum aerophilum. AB - The 16S rRNA genes of Pyrobaculum aerophilum and Pyrobaculum islandicum were amplified by the polymerase chain reaction, and the resulting products were sequenced directly. The two organisms are closely related by this measure (over 98% similar). However, they differ in that the (lone) 16S rRNA gene of Pyrobaculum aerophilum contains a 713-bp intron not seen in the corresponding gene of Pyrobaculum islandicum. To our knowledge, this is the only intron so far reported in the small subunit rRNA gene of a prokaryote. Upon excision the intron is circularized. A secondary structure model of the intron-containing rRNA suggests a splicing mechanism of the same type as that invoked for the tRNA introns of the Archaea and Eucarya and 23S rRNAs of the Archaea. The intron contains an open reading frame whose protein translation shows no certain homology with any known protein sequence. PMID- 8460171 TI - Analysis of homozygous mutant chimeric mice: deletion of the immunoglobulin heavy chain joining region blocks B-cell development and antibody production. AB - Using a recently described method for efficiently deriving homozygous targeted alleles in embryonic stem cells, we produced chimeric mice whose tissues were derived partially from embryonic stem cells bearing homozygous deletion of the mouse immunoglobulin heavy-chain joining (JH) region. Characterization of these chimeric mice indicated that homozygous JH deletion leads to arrest of B-cell development at an early stage, resulting in a total lack of peripheral B cells and serum IgM. These results were confirmed in mice containing the homozygous JH deletion in their germ line. This novel B-cell-deficient mouse strain provides a tool for studying the recombination and expression of exogenous immunoglobulin genes introduced into the mouse germ line. PMID- 8460172 TI - [PAF-antagonists with a phospholipid structure. 5. Propanediol phospholipids with various substituted pyridinium and quinuclidinium head groups and variations of the phosphorus-nitrogen distance;synthesis, characterization and structure activity relationship]. AB - A series of 10 PAF-analogues, structurally modified in position C-2 (n-propyl) and position C-3 (polar head group) were synthesized, and the PAF-inhibitory potencies was evaluated using PAF-induced aggregation of human blood platelets in vitro. Structure-activity relationships revealed, that the PAF-inhibitory activity is strongly influenced by the distance between phosphate and onium center and the structure of the substituted heterocyclus. The best activity was observed by 3,5-dimethylpyridinium- and 4-ethylpyridinium derivative with a P-N distance of 6 methylene groups (IC50 = 1.9 x 10(-6) mol/l and 2.7 x 10(-6) mol/l). PMID- 8460173 TI - [The effect of food on the pharmacokinetics of drugs]. PMID- 8460174 TI - [Antiarrhythmia active amidinohydrazone substituted benzophenones. 5. The stability of (Z)-2-amino-5-chlorobenzophenone amidinohydrazone acetate in solution]. AB - The aqueous solution of the title compound can be used for injection for one year if it is stored at room temperature and under light protection. Under these conditions 8% of the E-isomer are produced. The reaction is reversible at day light. Red coloured products of decomposition are formed by long lasting influence of light. At higher temperatures or at sterilisation several products of decomposition are formed which structure is elucidated. For these decomposition a scheme is proposed. PMID- 8460175 TI - [Determination of drug availability from commercial topical formulations with a multilayer membrane model]. AB - Using the multilayer membrane system (MMS) the drug availability of four drugs from commercial topical formulations are determined. It was found that the availability differs when commercial formulations of beta-methasone-17-valerate, hydrocortisone, diclofenac-Na and clotrimazole were studied. It is shown that the drug availability for characterizing topical formulations has to be taken into account. The MMS applied in this study can be used for the determination of this parameter. PMID- 8460176 TI - Amino acid norfloxacin derivatives as prodrugs. PMID- 8460177 TI - The fate of suctioned and surgically removed fat after reimplantation for soft tissue augmentation: a volumetric and histologic study in the rabbit. AB - The use of autologous fat transplantation has seen renewed popularity with the recent advent of liposuction as a body recontouring technique. However, clinicians are still faced with uncertainty concerning the ultimate volume maintenance of the transplanted fat graft at its recipient site. This study was initiated to examine and evaluate the changes in volume of suctioned versus surgically excised fat grafts over a 9-month period in the New Zealand White rabbit. Fat grafts of equal volume were harvested from the groin using standard suction and surgical techniques and transferred into isolated pockets in the ear. Results demonstrate that both suctioned and surgically removed fat grafts undergo significant volume reduction. However, surgically excised fat maintains its volume (42.2 percent; n = 16) better than suction-assisted fat grafts (31.6 percent; n = 16; p < 0.05). Histologic examination showed that fibrous connective tissue was more prevalent in the suctioned fat grafts than in the surgically removed fat grafts. PMID- 8460178 TI - Bone-graft reconstruction of the monkey orbital floor with iliac grafts and titanium mesh plates: a histometric study. AB - Bone-graft reconstruction of large orbital defects has been difficult because of a lack of marginal support of the grafts and unpredictable resorption. A titanium mesh orbital plate has been developed to provide this marginal support for bone grafts. However, the problem of unpredictable bone-graft resorption remains. To determine if this plate has any effect on graft resorption, this study was designed to quantitate the dimensions and composition of bone autografts (1) with and without titanium plate support and (2) in the anterior and posterior orbit. Bilateral full-thickness large orbital floor defects were surgically created in five monkeys, and a titanium orbital floor plate was fixed with screws into the right orbit. Two iliac crest grafts were measured and placed transversely and without fixation in each orbit, one anterior and the other posterior to the axis of the globe. The orbits were retrieved 28 weeks after surgery and were analyzed histologically and histometrically. Comparison of the supported and nonsupported grafts revealed no differences in their histologic appearance. There were three significant histometric findings: (1) resorption of bone was similar for those grafts which spanned an orbital floor defect and those which were supported by a titanium plate; (2) resorption of grafts in the posterior orbit did not differ from that of grafts in the anterior orbit; and (3) resorption of approximately one-third of bone-graft thickness and width had taken place during the 28-week study interval. We conclude that the benefits of bone-graft support by a titanium mesh orbital floor plate are not offset by any alteration in bone-graft resorption. PMID- 8460179 TI - The physician cost of treating maxillofacial trauma. AB - Treatment of maxillofacial trauma patients can be difficult for the surgeon because of patient noncompliance, frequent litigation, and poor payment habits. Numerous studies have examined the socioeconomic aspects of trauma as they affect hospitals and communities, but none to date has looked at the socioeconomic aspects of trauma as they affect the surgeon. This study is based on a retrospective sequential review of the medical records of 50 patients who suffered malar complex fractures and were treated with operative reduction at a university medical center. These patients are compared with a sequential series of 20 patients with basal cell carcinoma of the cheek treated by the same surgeon. The maxillofacial trauma group paid an average of 57 percent of their bills and had cases that involved lawyers 30 percent of the time, and only 54 percent of the patients kept all their postoperative appointments. All these figures were statistically different from those of the basal cell carcinoma patients, who paid an average of 90 percent of their bills and had no cases that involved lawyers and 95 percent of whom kept all postoperative appointments. These findings support the premise that maxillofacial trauma patients are difficult patients to treat and that unless the trauma reimbursement system is revised, plastic surgeons may limit their treatment of trauma in the future. PMID- 8460180 TI - Management of large scalp defects with local pedicle flaps. AB - Recent reports have emphasized free-flap reconstruction for large defects of the scalp and calvarium following resection of tumors, infection, or trauma. In most cases, however, a carefully planned local transposition or rotation flap may be equally effective, and the technical difficulties and donor-site problems associated with microsurgical tissue transfer are then avoided. We present 10 patients whose full-thickness scalp defects covered an average area of 241 cm2, or 27 percent, of the skull surface. Although this series included defects as large as 450 cm2, or 50 percent, of the skull surface area, each was easily managed with a local pedicle flap transfer. Four patients were reconstructed with parietal scalp transfer, four with an occipital scalp flap, and two with temporal scalp transfer. The technique and results are discussed. PMID- 8460181 TI - Surgical management of temporomandibular joint ankylosis in the pediatric population. AB - The treatment of temporomandibular joint ankylosis requires excision of the involved structures and immediate reconstruction. This paper presents a consecutive series of nine pediatric patients (mean age 7.7 years) who underwent a standardized treatment protocol to 13 affected joints. Four patients had unilateral temporomandibular joint ankylosis, five bilateral. One child required bilateral release but only unilateral reconstruction. Radiographic evidence demonstrated bony ankylosis in a total of 13 joints. Two patients had undergone surgical intervention of the temporomandibular joint before presentation to the authors. Two patients had preoperative temporomandibular joint pain. The cause of ankylosis was primarily traumatic or congenital. Our operative protocol included excision of the involved ankylotic structures through a coronal and Risdon incision, followed by immediate costochondral grafting. Fixation with miniplates and screws allowed for early mobilization. For unilateral patients, maximal incisal opening was improved from 5.4 mm before surgery to 24.8 mm after it, and for bilateral patients, from 6.0 to 17.5 mm. Mean follow-up was 2 years; only one patient was followed for less than 1 year. Pain symptoms were relieved after surgery. Perioperative complications were minimal, with no evidence of infection, facial nerve injuries, or bleeding. Patients with unilateral or bilateral ankylosis of traumatic cause achieved satisfactory functional results after surgery, while those in our bilateral congenital patients were far more limited. Rationales for this divergence in results are presented. PMID- 8460182 TI - The design of tongue flaps for the closure of palatal fistulas. AB - This paper presents the author's experience with thin (3-mm) tongue flaps used to close large anterior palatal fistulas. This technique was used successfully in 12 patients with fistulas following surgery for cleft palate. One forked flap and one mushroom-shaped flap that were used to close irregularly shaped fistulas are described. All flaps survived, and there was a partial recurrence of one fistula in only one patient. The results of this series confirm that the thin tongue flap is a safe and reliable technique for the closure of large palatal fistulas even when tailored to fit irregularly shaped defects. PMID- 8460183 TI - Reconstruction of the burned external ear using a Medpor porous polyethylene pivoting helix framework. AB - This paper describes a new technique using a Medpor porous polyethylene pivoting helix framework for reconstruction of the burned auricle. The polyethylene framework is composed of two distinct components, a curved shape that represents the helical rim which pivots around a base component. This framework is covered with a temporoparietal fascia flap and a skin graft that is chosen to match the adjacent resurfaced facial burn. The porous framework then becomes rapidly vascularized with soft-tissue ingrowth and collagen deposition. The pivoting helix design can be used to create an auricle of almost any size or projection. The helix can move independently and can be compressed against the head in the event of external pressure on the ear. The resultant ear reconstruction is extremely durable and remains flexible over time. Twenty-six consecutive ear reconstructions were performed using this method over a 2-year period. Two exposures occurred which were managed without removal of the implant. All reconstructions successfully restored an ear that was both aesthetically pleasing and functional so as to provide support for a pair of eyeglasses. The Medpor porous polyethylene pivoting helix framework offers an excellent solution for a difficult reconstructive problem. PMID- 8460184 TI - Early adipofascial flap coverage of deep electrical burn wounds of upper extremities. AB - The adipofascial flap is a useful method for treating deep electrical burn wounds requiring early definitive wound closure to preserve vital structures and function. In the past 2 years, 14 deep electrical burns of the upper extremities involving exposure of tendon, nerve, bone, or blood vessels requiring immediate vessel reconstruction were covered with an adipofascial flap. The latter was a local random turnover flap of the fascia and its overlying subcutaneous fat. All flaps were successfully elevated and applied to severe wounds in order to preserve underlying structures. There were no serious complications. Tendon gliding under the flap was found to be excellent during second reconstructive surgical procedures. The reconstructed limbs had satisfactory preservation of function. PMID- 8460186 TI - The detection of breast cancer after augmentation mammaplasty. AB - Thirty-five patients treated for 37 cases of breast cancer after augmentation mammaplasty were analyzed. All augmentations were performed with silicone gel prostheses at a mean age of 38 years (range 24 to 59 years). The mean interval from breast augmentation to the detection of breast cancer was 7.5 years. Physical examination demonstrated a palpable breast mass in 35 of the 37 cases (95 percent). The pathologic staging was in situ 3 (8 percent), local 18 (49 percent), and nonlocal 16 (43 percent). Standard compression mammography was performed in 31 patients prior to breast biopsy. Abnormalities were detected in 17 (54.8 percent). Palpable masses were visualized in only 12 (38.7 percent). Ultrasound was utilized successfully in 3 patients with palpable masses to guide fine-needle aspiration biopsy. Standard two-view mammography has a low sensitivity in detecting palpable cancers in patients who have undergone augmentation mammaplasty. Ultrasound should be evaluated as a routine adjunctive screening method in this group of patients. The clinical detection of breast cancer, as evidenced by pathologic staging, is not delayed. PMID- 8460185 TI - Rupture and aging of silicone gel breast implants. AB - This retrospective study evaluated aging and rupture of silicone gel breast implants in 31 women. The implants were removed at a large multispecialty clinic from 1987 to 1990. The implants ranged in age from 1 to 17 years. Of the 51 implants removed, 27 were ruptured, 7 were leaking, and 17 were in good condition. Common reasons for implant removal were discomfort, firmness, or a mass adjacent to a ruptured implant. Injury to the breast (trauma or mammography) led to a removal in only 4 patients. Closed capsulotomies were common in both ruptured and intact groups. The number of intact implants declined over time. All implants older than 10 years were leaking or ruptured. There was a positive correlation between the duration of implantation time and the number of ruptured and leaking implants. PMID- 8460187 TI - Rapid response of traumatic and medical tattoos to treatment with the Q-switched ruby laser. AB - Traumatic tattoos can be very difficult to remove. Excision is often not possible because of the extent of the tattoo, and dermabrasion may not be able to reach the area of pigment without significant scarring. Six patients with traumatic (n = 5) or medical (n = 11) tattoos were treated with the Q-switched ruby laser with complete or nearly complete resolution after one to six treatments without cutaneous scarring or permanent pigmentary alteration. PMID- 8460188 TI - Efficacy of cycled hyperinflation for rapid tissue expansion. AB - Temporary hyperexpansion at each filling session has previously been confirmed to increase the inflation volume in a conventional expansion procedure. This study employed eight young pigs to evaluate the effect of hyperinflation of this type in rapid expansion performed on 10 consecutive days. Hyperinflation to 120 mmHg for 4 minutes and deflation to 40 mmHg for 2 minutes was repeated five times on the experimental side. This cycled hyperinflation was found to increase the filling volume by 49 percent when compared with the contralateral side, which was not cycled or hyperinflated (control) (p < 0.01). The increase in surface area of the entire skin over the balloon was 178.1 percent in the hyperinflation group and 132.8 percent in the controls (p < 0.01). The actual expansion in surface area was not significantly different: 44.4 percent in the hyperinflation group and 45.7 percent in the control group. The additional gain of skin by cycled hyperinflation was the result of recruitment. The control group required 5 more days to achieve the same amount of skin but resulted in more true expansion and less recruitment. It is concluded that the cycled hyperinflation technique may shorten the time period of the whole reconstruction procedure but may produce an aesthetic deformity and flap necrosis. PMID- 8460189 TI - The deep inferior epigastric artery free skin flap: anatomic study and clinical application. AB - We carried out an anatomic study to create the efficient surgical technique of elevating the inferior epigastric artery free skin flap. The deep inferior epigastric artery bifurcates into the lateral and medial branches. The former usually is larger in diameter and has many skin perforators slightly lateral to the midline of musculature. When a vascular pedicle skin flap is lifted without attaching the rectus abdominis muscle or its anterior sheath, it seems more efficient if the flap uses the skin perforator belonging to the lateral branch. This is so because entry of the inferior epigastric artery is from the lateral side of the rectus abdominis muscle and the lateral branch runs slightly lateral to the midline of the musculature and parallel to the run of the muscular fibers. This would be easier technically and would minimize the damage to the muscle when detaching the lateral branch. PMID- 8460190 TI - The radial forearm flap donor site: should we vein graft the artery? A comparative study. AB - Controversy exists in the literature regarding reconstruction of the radial artery after elevation of the radial forearm flap. The literature suggests that reconstructing the radial artery with a vein graft is an important aspect in the use of this flap. In our experience, this has never been performed with no sequela. We examined 13 consecutive patients who underwent radial forearm flaps for head and neck reconstruction over a 28-month period. The patients were examined and questioned about the function of their upper extremities in hope of evaluating the postoperative vascular status in each. Median follow-up was 6 months, with a range of 1 month to 24 months. No patient had preexisting trauma or congenital abnormality of either arm, so that the nondonor arm could be considered as a control for each patient. Evaluation consisted of history and physical examination. The following parameters in each patient were carefully accumulated: grip strength, cutaneous blood flow measured by using a laser Doppler flowmeter, transcutaneous oxygen levels, digital/brachial blood pressure ratios, cutaneous temperature from thumb/index and thumb/small pinch, and rapid rewarming at 1-minute and 5-minute intervals after cold immersion for 2 minutes. The radial forearm flap was elevated in each patient in the nondominant extremity. Grip strengths ranged from 19 to 77 kg, with a median of 30 kg. Early rewarming of the thumb/index was also an average of 1.5 degrees less than the temperature in the control arm and was statistically significant to (p = .01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8460191 TI - Reinnervated free muscle transplantation for extremity reconstruction. AB - Reinnervated free muscle transplantation was used to rehabilitate severely impaired extremities in patients with brachial plexus palsy and for functional limb salvage in cases of traumatic muscle loss or radical excision of a malignant soft-tissue tumor. Fifty-eight reinnervated free muscle transplantations were implanted in 46 patients. Twenty-four patients had simultaneous reconstruction of two functions, such as finger and elbow flexion lost to brachial plexus palsy; 12 patients underwent double muscle transplantation; 15 patients received free muscle transplants for limb salvage after tumor excision in an extremity; 6 transplants replaced traumatic muscle loss; and 1 was used for reconstruction of finger flexion after poliomyelitis. Twenty-six latissimus dorsi, 25 gracilis, and 7 rectus femoris muscles were used as donors. All muscles survived. The postoperative follow-up ranged from 18 months to 4 years. The speed and extent of reinnervation of the transplanted muscle depended on the choice of recipient nerve, the patient's age, and the occurrence of postoperative vascular complications. Neurotization by the spinal accessory nerve or the posterior interosseous nerve resulted in the most rapid recovery. The administration of postoperative chemotherapy did not delay recovery of function. Free muscle transplantation is consistently successful and provides a functional extremity in severely handicapped patients. PMID- 8460192 TI - Laserflowgraphy: a new visual blood flow meter utilizing a dynamic laser speckle effect. AB - We developed a visual laser blood flow meter that is capable of providing two dimensional color graphic representations of blood flow distribution for a given area by utilizing a dynamic laser speckle effect. The device is called the laserflowgraph. The principle and configuration of this flowmeter, comparison with the 133Xe clearance method, difference from thermography, and clinical uses of this flowmeter in flap monitoring are presented. Flow level of the laserflowgraph was significantly correlated with blood flow rate determined by 133Xe clearance in observations on the forearms of normal volunteers. The laserflowgraph reflected blood flow through the region between the skin surface and the deeper region of the papillary layer of the dermis. The laserflowgraph is a highly useful, practical, and reliable tool for assessing cutaneous blood flow and is expected to be applicable to various clinical fields. PMID- 8460193 TI - Construction of a neovagina with preservation of the glans penis as a clitoris in male transsexuals. AB - In 20 male-to-female transsexual patients, a neovagina has been constructed using a combination of penile and scrotal flaps. By dissecting the dorsal vessels and nerves of the penis from the base to the tip, the blood supply and sensation to the glans have been preserved. After resection of the corpora cavernosa, the glans has been left as an innervated island flap and repositioned as a clitoris. There were few complications. Circulatory problems in the flaps resulted in short vaginas in three patients. Stricture of the urethral meatus and excessive length of the urethra were easily corrected with another operation in three patients. Nineteen of the patients expressed an excellent sexual sensation of the clitoris, and all 20 were very satisfied with both the cosmetic and functional results. PMID- 8460194 TI - Construction of the fixed part of the neourethra in female-to-male transsexuals: experience in 53 patients. AB - Genital construction in female-to-male transsexuals should ideally involve the creation of a competent neourethra, allowing the patients to void while standing. A short review of the literature on this subject is given. In our hospital, construction of the fixed part of the urethra up to the level of the clitoris has been accomplished using an anterior vaginal flap as described by Thompson and by Bouman in 46 subjects. Initially, serious complications such as vesicovaginal and urethrovaginal fistulas and urinary incontinence were encountered in this series. Subsequently, in experienced hands, this seems to be a technique with few risks. Formation of a urethrocutaneous fistula at the level of the female external urethral orifice can be successfully prevented using this flap. The problem of neourethral urine residue has still to be solved. PMID- 8460195 TI - Constructing a scrotum in female-to-male transsexuals. AB - Genital construction in female-to-male transsexuals also should involve giving the labial region a scrotum-like appearance. A review of the literature on this subject is given. In our hospital, the construction of a scrotum in which testicular prostheses are implanted has been performed usually in combination with lengthening of the pars fixa of the urethra. A bifid scrotum is constructed using a V-Y advancement of the labial skin. Although implant expulsion (in 7 percent) and dislocation of implants (in 11 percent) were encountered in this series of 50 patients, the technique itself is easy to perform and seems to have few major drawbacks. The scars are small and hidden in the scrotal folds and hair. Tissue expansion prior to implantation of the testicular prostheses in the labial skin has proven to be unnecessary with this technique. PMID- 8460196 TI - Complete congenital duplication with incomplete separation of a lower extremity. AB - A case of a boy with complete duplication of the lower extremity and separation below the lower leg was described. Although x-ray examination revealed no femur, operation revealed a cartilage expected to become the femur in the future. A classification of duplication and separation of the lower extremity is proposed. The method and course of treatment in the present case were described in detail, including the application of tissue expanders on the deformity of the knee joint accompanied by a shortening of the sciatic nerve. PMID- 8460197 TI - Bilateral lateral vermilion border transposition flaps to correct the "whistling lip" deformity. AB - A simple method of transposing bilateral lateral vermilion border flaps into the midposterior line of the prolabium to correct the "whistling lip" deformity is presented. This method makes it possible to decrease the upper lip tension, deepen the labiogingival sulcus, and reconstruct a peaked tubercle. PMID- 8460198 TI - Extremely thinned inferior rectus abdominis free flap. AB - To overcome a major drawback of the inferior rectus abdominis free flap, unpleasant thickness in a obese patient, a method of extreme thinning of the flap has been introduced. Extreme thinning is achieved by resecting a large volume of subcutaneous fatty tissue of the flap using scissors without damaging the subdermal vascular plexus. According to our clinical experience, it is supposed that the extremely thinned portion can be prepared safely when the width-to length ratio is within 1:2. PMID- 8460199 TI - Salvage by tattooing of areolar complications following breast reduction. AB - Even partial areolar loss following breast reduction must be considered an aesthetic disaster for which there are few surgical options for correction. Tattooing, as directly borrowed from postmastectomy techniques for nipple-areola creation, permits reconstitution of a reasonable facsimile of the areola. Discoloration or loss of nipple contour as may also occur in composite nipple areola grafts may be enhanced and/or an illusion of nipple projection achieved by appropriate regional micropigmentation. Tattooing provides another simple method that can be repeated with virtually no morbidity for salvage of an unacceptable result following breast reduction. PMID- 8460200 TI - Slow, gradual external fixation distraction for treatment of postburn knee flexion contracture. AB - Although surgical release and reconstruction have been used extensively to treat severe postburn knee flexion contractures, the degree of correction is sometimes unsatisfactory, and the procedure is not exempt from significant complications. Based on the principle of slow, gradual external fixation distraction, we have designed a triangular articulated frame to be mounted with the ASIF-BM fixator to deal with joint flexion contractures. One successfully treated patient is reported. This is a percutaneous surgery, with very mild aggression to the patient and very low iatrogenic risks. The technique is easy, the degree of correction may be almost complete, and the hospital stay is very short because it is an ambulatory surgery. PMID- 8460201 TI - Clitoroplasty for clitoromegaly due to adrenogenital syndrome without loss of sensitivity. AB - For preservation of postoperative sensitivity of the glans clitoris, clitoroplasty for clitoromegaly due to adrenogenital syndrome is reported. The operative technique includes the removal of ventral corporal tissue, taking care to avoid damage to the dorsal neurovascular bundle. A small lump of glandular tissue, which is connected with the neurovascular bundle, is left over and affixed to the pubic bone. Postoperative appraisal of patients in whom this technique has been applied is satisfactory. However, precise assessment of glandular sensation is not possible because of the patients' young ages. Follow up investigation at puberty is necessary for a final, proper appraisal. PMID- 8460203 TI - Repositioning the orbicularis oculi muscle. PMID- 8460202 TI - Avoiding needle sticks in the operating room. PMID- 8460204 TI - Laparoscopically assisted vaginal hysterectomy in female-to-male transsexuals. PMID- 8460205 TI - Reducing blood loss associated with lipectomy. PMID- 8460206 TI - An aid to pedicle dissection. PMID- 8460207 TI - Repositioning the orbicularis oculi muscle in composite rhytidectomy. PMID- 8460208 TI - The extended V-Y flap. PMID- 8460209 TI - Liposculpture sans suction. PMID- 8460210 TI - Breast reconstruction in women treated with radiation therapy for breast cancer. PMID- 8460211 TI - Patch esophagoplasty. PMID- 8460212 TI - "Trion" code for radiation action calculations and its application in microdosimetry and radiobiology. AB - A code for calculations of electron, ion and photon radiation action on tissue equivalent matter (water vapor) by the Monte Carlo technique is presented. The new "fluctuation detector" method is efficient in evaluating of probability distributions and moments of absorbed energy and number of ionizations in small sites. Spatial and energy distributions of particles fluences and fluctuation characteristics of radiation action on spherical and thread-like sites of nanometer diameter are compared with various experimental and theoretical data and discussed. Non-equivalence of energy absorption and ionization events and consequences of that non-equivalence are numerically analysed. As an example of radiobiological application the yield of single- and double-strand breaks of DNA is calculated in a threshold model. PMID- 8460213 TI - Clonal heterogeneity in delayed decrease of plating efficiency of irradiated HeLa cells. AB - The clonogenic potential of progeny of irradiated HeLa cells was studied at different times after single doses of 4-12 Gy. The dose-dependent decrease in plating efficiency that was observed resembled the effect termed "delayed lethal mutation" by Seymour et al. (1986). The effect decreased with time after irradiation. Individual clones of irradiated and non-irradiated cells were isolated, expanded and replated 5 weeks after irradiation, i.e., after between 200,000 and 1,000,000 progeny had formed from the individual parent cell. The plating efficiency of progeny of unirradiated cells did not vary much, whereas clonal progeny of irradiated cells had plating efficiencies ranging from 3% to 76%. The plating efficiency was not related to the cell number in the original clone. PMID- 8460214 TI - The effect of cold after whole-body irradiation of the mouse. AB - Mice were placed in a cold environment (4 degrees C) directly after whole-body irradiation. Those irradiated with a lethal dose showed higher lethality than mice irradiated with the same dose but placed in room temperature. The response was also altered after irradiation with a sublethal dose. At various periods after irradiation mice were injected with 125IUdR, the tissue uptake of which is an index of DNA synthesis. The result showed that cold treatment after irradiation caused slower cell renewal in the spleen and bone marrow, but that the thymus was only marginally affected. Furthermore, the concentrations of erythrocytes in the peripheral blood reached a lower level in the cold-treated group. Finally, the levels of the thyroid hormones T3 and T4 in the blood were measured and it was found that the T3/T4 ratio was higher in the cold-treated mice. It is suggested that during prolonged exposure to cold after irradiation the cell recovery in the haemopoietic system is exposed to hormonal action that induces significant alterations in the postirradiation cell kinetics. PMID- 8460215 TI - Rubidium transport in irradiated vitamin-E-deficient bone marrow cells. AB - We showed previously that the Rb+ transport rate in bone marrow cells (BMC) of vitamin-E-deficient mice is significantly lower than that in BMC of euvitaminotic mice. It is now evident that 4 h after whole-body, low-dose (0.01-1.0 Gy) gamma irradiation of avitaminotic mice, there is an increase in the rate of Rb+ transport. This increase is quite pronounced, exceeding at all dose levels the rate of Rb+ transport in euvitaminotic mice exposed to the same radiation dose. PMID- 8460216 TI - Influence of a stationary magnetic field on acetylcholinesterase in murine bone marrow cells. AB - A thirty-minute exposure of mice to a homogeneous stationary magnetic field (SMF) of 1.4 Tesla at either 27 degrees C or 37 degrees C body temperature causes an inhibition of about 20 per cent of acetylcholinesterase (AChE, E.C. 3.11.7) in murine bone marrow cells (BMC) after 3.5 and 2 h, respectively, at the two aforementioned body temperatures. The extent of enzyme inhibition is independent of ambient temperature, but dependent on the time after exposure. This initial inhibition of AChE activity is followed by a limited recovery which is dependent upon the temperature during exposure to the SMF and remains incomplete even 15 h afterwards. We describe here certain enzymologic properties of AChE in BMC as well as inhibition studies with diisopropylfluorophosphate (DFP) to differentiate between AChE and nonspecific cholinesterases. PMID- 8460217 TI - On the mechanism of a 60-Hz electric field induced growth reduction of mammalian cells in vitro. AB - Data on 60-Hz electric field (EF) induced reduction in growth rate of plant roots have strongly supported the hypothesis that the effect is related to an EF induced transmembrane potential (Vim). An investigation was undertaken to determine if this hypothesis is also applicable to 60-Hz EF-induced reductions in growth rate of mammalian cells in vitro. Human lymphoblastic (RPMI 1788) and human carcinoma (HeLa) cells were selected for study, the former having a relatively small diameter (11.2 microns), and the latter having a relatively large diameter (15.4 microns). The 60-Hz EFs ranged from 430-1200 V/m in the culture medium. The growth rate of RPMI 1788 cells after 4-days was depressed by about 42% at a 60-Hz EF of 1000-1200 V/m with a response threshold occurring at 950 V/m; the Vim at the response threshold was 8 mV. There was no 60-Hz EF induced effect on HeLa cell growth rate of a Vim of 8 mV (60-Hz EF = 700 V/m); a statistically significant effect was achieved at Vim of 11 mV (950 V/m). The data support the hypothesis that above a threshold 60-Hz EF, Vim acts as the initial signal leading to growth rate reductions. PMID- 8460218 TI - Fat-suppressed three-dimensional MR imaging of the breast. AB - Rotating delivery of excitation off-resonance (RODEO) is a new magnetic resonance (MR) imaging pulse sequence that uses a jump return sine excitation on fat resonance to produce fat-suppressed, T1-weighted images. New three-dimensional MR imaging techniques were used to examine 57 women with abnormalities suspicious for breast cancer. MR imaging findings were compared with those of mammography in all cases and with those of other imaging techniques when appropriate. Thirty five specimens obtained at mastectomy were analyzed with rigorous pathologic examination that included imaging of the entire breast at 5-mm incremental sections. Histologic confirmation was obtained in 76 lesions in 47 patients. MR imaging helped detect 100% of malignant lesions, whereas mammography produced 33% false-negative findings. The use of RODEO in breast imaging is in the early investigational phases, but it has potential for supplementing mammography in the diagnosis of breast cancer. PMID- 8460219 TI - What ever happened to clinical medicine? PMID- 8460220 TI - Bilateral basal ganglia lesions: pediatric differential considerations. AB - Computed tomography (CT) and magnetic resonance (MR) imaging have dramatically improved the ability to visualize the deep gray structures of the basal ganglia (primarily, the caudate nucleus, putamen, and globus pallidus). Any process that alters cerebral metabolism can lead to basal ganglia damage. This article presents the spectrum of disease that may be seen with bilateral basal ganglia abnormalities in the pediatric population. A simplified approach to the differential diagnosis of these entities is based on acute versus chronic conditions and radiologic manifestations. Acute processes include hypoxia, hypoglycemia, carbon monoxide poisoning, hemolytic-uremic syndrome, osmotic myelinolysis, and encephalitis. Chronic conditions include inherited ("inborn errors of metabolism," Huntington disease, and dysmyelinating diseases) or acquired (sequelae of acute disorders) conditions that represent abnormal biochemical or structural processes within the basal ganglia. Elimination of acute causes gives little hope for improvement. Recognition of chronic disorders is important for counseling purposes, since most of these conditions have specific patterns of inheritance. PMID- 8460221 TI - MR imaging in the evaluation of female infertility. AB - Magnetic resonance (MR) imaging has proved useful in evaluating various conditions associated with female infertility. With T2-weighted pulse sequences, uterine zonal anatomy can be clearly delineated, and with images obtained in a plane coronal and perpendicular to the long axis of the uterus, the external uterine contour can be evaluated. This latter capability allows the differentiation of a bicornuate uterus from a septate one, a distinction that has not been possible with hysterosalpingography and that enables improved treatment planning. MR imaging accurately demonstrates leiomyomas, providing improved preoperative localization compared with that achievable with hysterosalpingography or ultrasonography, and may be useful in differentiating these tumors from adenomyosis. Endometriosis can be detected with MR imaging, but laparoscopy is more reliable for diagnosis and staging. Although the use of MR imaging is not indicated in every evaluation, the modality is valuable in certain settings, especially those that involve differentiation of congenital anomalies and localization of leiomyomas. In these settings, use of MR imaging can obviate more invasive procedures, such as laparoscopy. PMID- 8460222 TI - The emphysemas: radiologic-pathologic correlations. AB - There are several forms of emphysema that should be considered as distinct disease entities. No university accepted classification system of these forms exists, but correlations of autopsy findings in 1,823 cases over a 12-year period confirm that the radiographic and pathologic features of the emphysemas are readily understood when centrilobular, panlobular, paracicatricial, and localized types of the disease are recognized. Centrilobular emphysema associated with cigarette smoking is the most common form. Panlobular emphysema is associated with alpha 1-protease inhibitor deficiency and pathologically produces uniform enlargement of all air spaces, with a mild basilar predominance. Paracicatricial emphysema is seen adjacent to areas of parenchymal scarring. Localized emphysema represents focal enlargement or destruction of air spaces with otherwise normal lung. A clear understanding of the computed tomographic appearance of all forms of emphysema is essential for the correct diagnosis of parenchymal lung abnormalities. PMID- 8460223 TI - MR imaging in the evaluation of the chest after uncomplicated median sternotomy. AB - Although complications of median sternotomy are infrequent, they are associated with high morbidity and mortality. Current imaging modalities have proved to be of limited value in the evaluation of these abnormalities. The search for more efficacious means of assessment is continual. The appearance of the thorax was evaluated in 10 patients who were undergoing median sternotomy for coronary artery bypass graft surgery. Three serial magnetic resonance (MR) imaging examinations were performed on each patient. These examinations included a baseline preoperative study and two postoperative studies. Each patient included in the study had an uncomplicated postoperative clinical course. Usual postoperative findings included pleural effusions, pulmonary parenchymal abnormalities, mediastinal edema, and pericardial effusions. On the basis of this limited study, the authors believe that MR imaging is a feasible means of evaluating the chest after surgery. An appreciation of the normal postoperative appearance is essential before complications can be reliably identified and characterized. PMID- 8460224 TI - Spinal fixation. Part 1. Principles, basic hardware, and fixation techniques for the cervical spine. AB - Spinal fixation devices provide stability and restore anatomic alignment in the treatment of fractures, degenerative disease, infection, and tumors and correct congenital deformities such as those seen in scoliosis. The devices provide immediate stability but are not strong enough to withstand prolonged stress and eventually fail, in most cases, if bone fusion does not occur. Bone graft material is often used to promote fusion and to replace bone after resection. Internal fixation is used to maintain position and alignment and to prevent motion as the spine fuses. Plates and rods are attached to the vertebral body or posterior elements with wire, screws, and hooks. Screws and wire can also be used alone as a means of fixation. Surgical techniques and instrumentation have advanced in recent years, and radiologists are exposed to a myriad of devices. They need to be able to identify the various plates, screws, wiring techniques, and grafts used most commonly and to understand their function in the cervical spine for fusions and treatment of fractures and degenerative disease. PMID- 8460225 TI - Musculoskeletal manifestations of chronic renal insufficiency. AB - Abnormalities involving the musculoskeletal system are numerous and frequent in patients with chronic renal insufficiency (CRI). The most common radiologic manifestations of CRI are those referred to collectively as renal osteodystrophy: the findings seen in secondary hyperparathyroidism (bone resorption, periosteal reaction, and brown tumors), osteoporosis, osteosclerosis, osteomalacia, and soft tissue and vascular calcification. Bone resorption, the most frequent alteration of CRI, occurs in several locations (subperiosteal, subchondral, trabecular, endosteal, and subligamentous), whereas brown tumors and periosteal reaction are much less common. Osteosclerosis primarily affects the axial skeleton and may be the only sign of CRI. Osteoporosis and osteomalacia cause osteopenia and are not infrequent changes of CRI. The prevalence of calcifications increases with the duration of hemodialysis. The other major group of musculoskeletal abnormalities attributable to CRI includes aluminum deposition, amyloid deposition and destructive spondyloarthropathy, tendon rupture, crystal deposition, infection, and avascular necrosis. These changes are less common than those of renal osteodystrophy and are more frequently seen in patients who have undergone long term hemodialysis or renal transplantation. Recognition of musculoskeletal manifestations is important in the clinical management of patients with CRI. PMID- 8460226 TI - Anatomic variants in sinonasal CT. AB - The computed tomographic scans obtained in a series of 800 patients referred for evaluation for functional endoscopic sinus surgery were examined to determine the prevalence and significance of anatomic variants. Fifty-two normal variants were identified within two major groupings of primary bony abnormalities and sinus air cell extensions. Although 743 (93%) patients had one or more variants, the nature of the variants in many instances was such that 325 (41%) patients could be considered "endoscopically" normal. Among the remaining cases, variations of the septum and middle turbinates, with or without anterior ethmoid sinus extensions, were found, usually in recognizable combinations, that could produce significant obstruction of the drainage pathways. However, where such obstructive patterns existed, an equal prevalence of patients with and without sinus disease was found in the presence of the same variant combination. Thus, the presence of anatomic variations, singly or in combination, does not represent a disease state per se. PMID- 8460227 TI - Imaging spectrum of thrombo-occlusive vascular disease associated with antiphospholipid antibodies. AB - The association of antiphospholipid antibodies with unexplained thrombo-occlusive vascular disease is well known but often remains unrecognized. The most well studied clinical manifestation is venous thrombosis, but arterial occlusive disease involving multiple sites is also well documented. Twenty-six cases of thrombo-occlusive disease were observed in 22 patients over a 3-year period. Magnetic resonance imaging and angiography were used to make the diagnoses. None of the patients who underwent angiography or venography developed thrombolytic disease related to the puncture site. This group of patients with antiphospholipid antibody syndrome had a wide distribution of arterial and venous thrombotic disease. Radiologists should consider antiphospholipid antibody syndrome in the differential diagnosis when evaluating thrombo-occlusive vascular disease that is unexpected or occurs without risk factors. Knowledge of antiphospholipid antibody status has important implications for prognosis and therapy. PMID- 8460228 TI - From the archives of the AFIP. Extralobar sequestration: radiologic-pathologic correlation. AB - Extralobar sequestration is a rare congenital anomaly that consists of pulmonary tissue anatomically separate from normal lung and usually deriving its blood supply from systemic vessels. The lesion typically manifests in the newborn period or early infancy with symptoms of respiratory distress. Less frequently, patients present in childhood or adulthood. Grossly and microscopically, the lesion resembles lung tissue. The typical radiologic finding is a homogeneous soft-tissue mass in the lower hemithorax. However, these lesions can also occur in the mediastinum, within the diaphragm, and, rarely, below the diaphragm. Radiologic diagnosis rests on identification of the systemic vascular supply. Although angiography has been routinely used in the past in evaluating these lesions, other modalities including ultrasound, computed tomography, and magnetic resonance imaging may demonstrate the anomalous feeding and draining vessels. Treatment of extralobar sequestration consists of surgical excision of the mass. Prognosis is usually favorable in the absence of associated congenital anomalies. PMID- 8460229 TI - Integration of health care information systems. AB - Information is at the core of an effective response to virtually all of the new demands that health care institutions will face in the 1990s. New information that is differently organized, more timely, and more conveniently available will facilitate new interactions within the institution. The consistent theme of the new systems requirements introduced by CQI is tighter connection to the processes of patient care and integration of systems and data as those processes cross traditional organizational boundaries. Even the billing requirements are pushing in the same direction. Ironically, the dinosaurs descended from billing systems do not even perform very well as billing systems today, because payers want more clinical detail, in addition to information at very specific points during the patient-care process. This new management model changes our view of our systems. Instead of systems designed to create an after-the-fact record of patient care, we need to think in terms of systems that are part of the patient-care process. This is essential for the continuous monitoring and--when the process gets out of control--rapid intervention that are an intrinsic part of the process in the CQI model. Of course, these systems also produce a complete record as a by-product, but that is not their primary objective. These demands will test the capacities of many of our existing systems and will require the replacement of others. Like all complex processes, however, systems development is performed one step at a time. Each step is taken within the context of an overall goal but also presents an opportunity for learning. CQI is a new management model, and the system requirements are far from clear. Hence, we are likely to need a little continuous improvement in the systems, too. PMID- 8460230 TI - Requirements for PACS: users' perspective. AB - The applications for which picture archiving and communication systems (PACS) will be used must dictate the technological requirements. Technology-driven integrated PACS have been implemented and tested in a variety of clinical environments. PACS do not generate new revenues, albeit they may affect the bottom line of health care delivery systems through increased efficiency of radiology and, perhaps more important, of the other physicians who use radiologic services. User performance expectations require that trade-offs are evaluated and compromises are made when PACS are designed using currently available technology. In this report, functional requirements for clinical PACS are discussed. These include reliability, speed, ease of use, connectivity, and upgradability. The advantages and disadvantages of specific choices are presented from a utility perspective of an end user. PMID- 8460231 TI - Advanced computer applications in radiology: clinical applications. AB - Computers play a major role in bridging the gap between image generation and patient care by providing enhanced images that better meet the needs of referring physicians. Spiral computed tomography allows generation of three-dimensional images that are not affected by motion artifact. Volume rendering, a three dimensional reconstruction algorithm, yields images free of computer-generated artifacts and superior in quality. Currently, technologic computer advances play an important role in three clinical areas: orthopedic applications, oncologic applications, and prosthetic design. Three-dimensional imaging is especially valuable in fracture assessment because it allows exploration of image data to define the location of fracture fragments, the integrity of the joint space, and any possible displacement. With three-dimensional imaging, the extent of tumor spread into adjacent soft tissue or involvement of blood vessels can be determined, even in difficult anatomic areas. Volume rendering and increased computer speed allow greatly improved treatment planning for radiation therapy and custom design of orthopedic prostheses. Through the mutual understanding of goals between physicians and computer scientists, the computer can reach its full potential in medicine, resulting in improved patient care. PMID- 8460232 TI - Pediatric case of the day. Reninoma of the left kidney. PMID- 8460233 TI - Ultrasound case of the day. Herniating paraumbilical vein varix. PMID- 8460234 TI - General case of the day. Moyamoya syndrome in a child with sickle cell disease. PMID- 8460235 TI - [Does an effective adjuvant treatment in colorectal cancer exist?]. PMID- 8460236 TI - [The usefulness of adenosine triphosphate in supraventricular paroxysmal tachycardias]. AB - With the objective to evaluate adenosine triphosphate (ATP) usefulness in supraventricular paroxysmal tachycardia (SPT), doses of 0.25 mg/kg, of ATP are administered fastly i.v. in bolus, to fifty consecutive patients with SPT resistant to vagal stimulation maneuvers. The effect achieved allowed to identify two groups: a) 39 patients in whom tachycardia was interrupted; b) 11 patients in whom tachycardia did not cease, but the induced transient provoked atrial ventricular (A-V) blockage allowed to identify the underlying mechanism of tachycardia (in 6 of them atrial tachycardia and in 5 atrial flutter). In both groups the ATP effect was present in less than 30 seconds. In seven patients (five from group (a) and two from group b) the QRS duration was over 0.12 s. Six patients had a left ventricular ejection fraction below 30%. Side effects were frequent, but always short. ATP could become the drug of choice in the treatment of SPT without response to vagal maneuvers, due to the fact that, to its therapeutic activity, it must be added its diagnostic usefulness, its fast action and metabolization, together with the fact that it does not induce severe side effects. PMID- 8460237 TI - [Mediterranean boutonneuse fever as a cause of arthritis and false-positive serology for Borrelia burgdorferi]. AB - Arthritis is a rare clinical manifestation of Mediterranean boutonneuse [correction of Botonous] Fever (MBF). We present the case of a female patient with MBF who was admitted with an acute monoarthritis with inflammatory fluid and, besides, had a false-positive serology to Borrelia burgdorferi, which we have not found published before. In the scientific literature reviewed we only found 12 cases of MBF and arthritis. We discuss its probable pathogenic mechanism and underline the scarce importance which has been given to this manifestation in the large MBF series. PMID- 8460238 TI - [A malignant extra-adrenal pheochromocytoma. Apropos 2 cases]. AB - We present the case of two patients with extra-adrenal pheochromocytoma (left and right para-aorta abdominal) in which the pre-surgery search with metaiodobenzylguanidine-I-123 (MIBG-I-123) showed the existence of bone metastasis in skullcap, not previously suspected. In both patients a total resection of tumor was performed together with the bone lesions. These two cases confirm the great usefulness of MIBG-I-123 in the localization of metastasis in patients with malignant pheochromocytoma. At the same time we think that the resection of whole tumoral tissue through surgery is an adequate treatment when dealing with pheochromocytoma with isolated metastasis. PMID- 8460239 TI - [Cutaneous necrosis and rhabdomyolysis following the intravenous infusion of vasopressin]. AB - We describe the case of a patient with hepatic cirrhosis treated with an intravenous infusion of vasopressin to control an upper digestive hemorrhage, who developed distance cutaneous necrosis and rhabdomyolysis. We review the other cases published in the international scientific literature and we discuss the possible pathogeny of these complications. PMID- 8460240 TI - [Asymmetric polyarthritis in Sezary's syndrome]. AB - We present the case of a patient with negative serology asymmetric polyarthritis and erythematous-squamous cutaneous lesions of two years evolution, initially attributed to psoriasis, which histopathology (hyperkeratosis, epidermic infiltration due to atypical CD4+ lymphocytes with formation of Pautrier's microabscesses) together with hematological findings (persistent lymphocytosis with cells with cerebriform nucleus, 97% CD4+) allowed the diagnosis of Sezary's syndrome. To our knowledge, this is the eight documented case of arthritis in Sezary's syndrome and the first one with asymmetric chronic polyarthritis. PMID- 8460241 TI - [The clinical classification of hypertensive cardiopathy depending on the degree of cardiac involvement]. PMID- 8460242 TI - [The real ability to cure acute lymphoblastic leukemias with suspended therapy]. PMID- 8460243 TI - [Cholesterol in the pleural fluid]. PMID- 8460244 TI - [Sjogren's syndrome, idiopathic thrombopenia and hepatitis C]. PMID- 8460245 TI - [An atypical presentation of a fusiform-cell thymoma]. PMID- 8460246 TI - [Toxic cholestatic hepatitis due to droxicam]. PMID- 8460247 TI - [A tuberculotic subcutaneous abscess as the form of presentation of the acquired immunodeficiency syndrome]. PMID- 8460248 TI - [Acute pericarditis associated with Crohn's disease]. PMID- 8460249 TI - [The treatment of a case of recurrent oral aphthosis with pentoxifylline]. PMID- 8460250 TI - [IgG and IgA deficiency with hyper IgM]. PMID- 8460251 TI - [Theophylline-induced convulsions]. PMID- 8460252 TI - [A muscular abscess due to Nocardia asteroides: a possible complication of insulin therapy]. PMID- 8460253 TI - Survival and development of ivermectin-resistant or susceptible strains of Haemonchus contortus under field and laboratory conditions. AB - The free-living development of three strains of Haemonchus contortus was studied in two experiments. Day 21 faecal samples were collected from lambs infected with either a susceptible strain, a laboratory-selected ivermectin (IVM) resistant strain or a South African field strain showing multiple anthelmintic resistance, which included IVM. No eggs hatched in samples cultured at 4 or 10 degrees C. At 22 degrees C the laboratory-selected strain showed the highest rate of development while at 27 degrees C the susceptible strain produced the highest yield of third stage larvae (L3): at both temperatures the field strain showed the lowest percentage development to L3. The second experiment was a field study carried out in southern Brazil. Faeces containing either an IVM-susceptible or an IVM-resistant strain of H contortus were placed in two series of grass plots during each of three summer months. Soil subsequently yielded more larvae than did grass suggesting migration or mechanical transport into the soil. For plots contaminated during the first two months there was no significant difference in recovery rate between the two strains (P > 0.05). When contamination occurred during the third month, the IVM-resistant strain produced significantly higher recovery rates (P < 0.05) from both pasture and soil. PMID- 8460254 TI - Skeletal muscle histochemistry in male and female Andalusian and Arabian horses of different ages. AB - Muscle biopsies were taken from the middle gluteal muscle of 143 untrained horses (83 Andalusians [AN] and 60 Arabians [AR]) ranging from 10 days to 24 years old. The horses were separated according to breed and sex and allotted to five age groups: A, 0 to three months; B, yearlings; C, two to three years; D, five to 10 years; and E, 11 to 24 years. There was an increase in the percentage of type I fibres (about 100 per cent) as well as a decrease in the percentage of type IIB fibres (AN, 50 per cent; AR, 40 per cent) over the five age groups. The percentage of type IIA fibres rose significantly over the first two or three age groups. The overall decrease in the subgroup IIB fibres with age was proportionally greater for IIB oxidative fibres (AN, 72 per cent; AR, 68 per cent) than for IIB non-oxidative fibres (AN, 5 per cent; AR, 34 per cent). The mean cross-sectional area of all three fibre types increased significantly with age. In any given age group, the mean relative cross-sectional area occupied by IIA fibres in the biopsy specimens was significantly greater in stallions than in mares, at the expense of IIB fibres. PMID- 8460255 TI - Red cell-bound immunoglobulins and complement measured by an enzyme-linked antiglobulin test in dogs with autoimmune haemolysis or other anaemias. AB - A direct enzyme-linked antiglobulin test (DELAT) was used to measure IgG, IgM, IgA and C3 bound to the red blood cells (RBC) of anaemic dogs. One or more of these parameters was raised in 78 per cent of the cases tested, and elevated levels of bound IgG, IgM, IgA and C3 was the most common pattern recorded. When the DELAT-positive animals were divided into two groups on the basis of clinical findings, the two categories differed serologically. Cases diagnosed clinically as primary autoimmune haemolytic anaemia (AIHA) were typified by the demonstration of specific antibody binding to RBC, had significantly higher levels of RBC-bound IgG (P < 0.001) and IgM (P < 0.02) and included a significantly (P < 0.01) higher proportion of the dogs with at least three DELAT parameters raised. The second group comprised the DELAT-positive dogs with other diseases. In most of these cases, RBC-specific antibody was not detectable and there was a significant (rs = 0.62, P < 0.001) relationship between RBC-bound and serum IgG levels, suggesting that the immunoglobulin was reacting with the RBC non-specifically in a concentration-dependent manner. It is concluded that elevated levels of RBC-bound immunoglobulin and, or, complement are detectable with the DELAT in most anaemic dogs, but that this finding is not necessarily associated with autoimmune haemolysis. PMID- 8460256 TI - Kinetic disposition, systemic bioavailability and tissue distribution of salinomycin in chickens. AB - Salinomycin was administered to chickens orally and intravenously to determine blood concentration, kinetic behaviour, bioavailability and tissue residues. The drug was given by intracrop and intravenous routes in a single dose of 20 mg kg-1 body-weight. The highest serum concentrations of salinomycin were reached half an hour after oral dosage with an absorption half-life (t0.5(ab)) of 3.64 hours and elimination half-life (t0.5(beta)) of 1.96 hours. The systemic bioavailability percentage was 73.02 per cent after intracrop administration, indicating the high extent of salinomycin absorption from this route in chickens. Following intravenous injection the kinetics of salinomycin can be described by a two compartment open model with a t1/2(alpha) of 0.48 hours, Vd ss (volume of distribution) of 3.28 litre kg-1 and Cl(beta) (total body clearance) of 27.39 ml kg-1 min-1. The serum protein-binding tendency of salinomycin as calculated in vitro was 19.78 per cent. Salinomycin concentrations in the serum and tissues of birds administered salinomycin premix (60 ppm) for two weeks were lower than those after administration of a single intracrop dose of pure salinomycin (20 mg kg-1 bodyweight). The highest concentration of salinomycin residues were present in the liver followed by the kidneys, muscles, fat, heart and skin. No salinomycin residues were detected in tissues after 48 hours except in the liver and these had disappeared completely by 72 hours. PMID- 8460257 TI - Pharmacokinetic profile of sulphamonomethoxine-trimethoprim in horses after intravenous, intramuscular and oral administration. AB - The pharmacokinetic profile of a sulphamonomethoxine-trimethoprim (SMM-TMP) combination was investigated in five horses. The combination was administered intravenously, intramuscularly and orally at a constant dose of 20 mg SMM plus 4 mg TMP kg-1 bodyweight. Following intravenous administration both drugs dispersed rapidly with distribution half-lives of about 12 minutes for SMM and about 18 minutes for TMP. Elimination half-lives for intravenous, intramuscular and oral administration were closely similar, indicating that elimination was independent of administration route. Bioavailability of the drugs in aqueous solution was good: about 72 per cent and 84 per cent for SMM and about 84 per cent and 98 per cent for TMP following intramuscular and oral administration, respectively. It is concluded that SMM-TMP administered orally once a day at 20 mg and 4 mg kg-1 bodyweight, respectively, maintains therapeutic concentrations, whereas twice daily intramuscular administration would be more effective for treating systemic infections in the horse than the once a day regimen usually adopted in veterinary practice. PMID- 8460258 TI - Effect of cadmium on D-galactose transport across the small intestine of rabbits. AB - Cadmium compounds are found widely in the environment: for example, in food, water, soil and ambient air. The most important exposure route of animals to cadmium in the general environment is oral. The aim of the present work was to determine how cadmium acts on the intestinal absorption of sugars by rabbits. Results obtained show that cadmium decreases both D-galactose accumulation in the jejunum tissue, and mucosal to serosal transepithelial fluxes of this sugar, in a dose-dependent way. Furthermore, cadmium seems not to modify the sugar diffusion across the intestinal epithelium. This inhibitory mechanism is non-competitive and it is partly reversed with dithioerythritol (thiol groups protector). Therefore, these results suggest that cadmium decreases carrier-mediated intestinal absorption of sugar in rabbits. PMID- 8460259 TI - Non-invasive measurement of arterial blood pressure in dogs: a potential indicator for the identification of stress. AB - The reproducibility of indirect measurements of arterial pressure in dogs was assessed using the Dinamap 1846 SX oscillometric monitor and tail cuffs. Measurements on different days correlated excellently in 20 working dogs, with indistinguishable group means for systolic, diastolic and mean arterial pressure, whereas heart rates differed, though not significantly. The similarity of the means did not simply result from 'cancelling out' of individual variations; the rank correlation was also highly significant (P < 0.01 diastolic, P < 0.002 systolic). Remeasurement in the veterinary clinic, rather than 'neutral territory' showed significant increases in pressure but not heart rate. Anticipation of work raised systolic pressure whereas heart rate and diastolic pressure were unchanged. Exposure of a dog to a known stressor for that individual (sound) raised systolic and diastolic pressure as well as heart rate; diastolic pressure was the fastest to recover, heart rate the slowest. The data are compared with other observations on non-invasive blood pressure measurement in both dogs and humans. PMID- 8460260 TI - Comparison of bone volume and strength as measures of skeletal integrity in caged laying hens with access to perches. AB - Fractures in spent laying hens are now recognised as a major welfare problem; the objective of this work was to determine whether provision of perches for caged layers would increase bone strength, bone volume or both. Sixteen ISA Brown hens were housed from 18 to 72 weeks old in cages with perches and 16 in similar cages without perches. At the end of lay the birds' tibiotarsi were examined for strength by a three-point loading test and their tarsometatarsi for bone volume by histomorphometry. There was no significant effect of perches on tibiotarsal breaking strength. Hens from both groups showed evidence of osteoporosis, but it was more severe in the birds from conventional cages: tarsometatarsal trabecular bone volume was greater in the hens which had access to perches. A positive correlation was found between trabecular bone volume and the degree of day-time perch usage by individual hens. Provision of perches can have a slight but significant beneficial effect, at least for the leg bones, in increasing the bone volume of caged laying hens. PMID- 8460261 TI - Effects of perches on trabecular bone volume in laying hens. AB - Trabecular bone remodelling is known to be affected by loading or exercise, and thus exercise may effect the trabecular bone loss associated with osteopenia in laying hens. Sixteen ISA Brown hens were housed from 18 to 72 weeks old in cages with perches and 16 in similar cages without perches to examine the effects of the exercise afforded by perch provision on trabecular bone volume. At 72 weeks, mean trabecular bone volume in the proximal tarsometatarsus of birds with access to perches was significantly greater than in control birds, while medullary bone volume was not significantly different in the two groups. However, all the birds were considered osteoporotic, though to varying degrees, and the beneficial effects of perches were relatively minor. It was concluded that while trabecular bone loss may be reduced by perch provision, other factors are probably more influential in the development of the osteoporosis typical of laying hens. PMID- 8460262 TI - The use of thermostable Vero cell-adapted rinderpest vaccine as a heterologous vaccine against peste des petits ruminants. AB - The thermostable Vero cell-adapted rinderpest vaccine was evaluated in terms of immunogenicity as a heterologous vaccine against peste des petits ruminants. A titration to establish the minimum immunising dose was performed in American mixed breed goats by vaccinating test subjects with dilutions of Vero cell adapted rinderpest vaccine and then challenging 26 days later with virulent peste des petits ruminants virus. All animals were followed for virus neutralising antibodies against both rinderpest and peste des petits ruminants virus after vaccination and challenge. The antibody response to vaccination was primarily against rinderpest virus with very low levels of cross-reactivity to peste des petits ruminants virus. Following challenge, animals which possessed anti rinderpest neutralising antibodies remained clinically normal but mounted strong anti-peste des petits ruminants virus neutralising antibody responses indicating that replication of challenge virus took place without the induction of illness. The 50 per cent minimum goat immunising dose was 3 tissue culture infectious doses 50 per cent (TCID50) as established by serological response and protection against challenge. The thermostable Vero cell-adapted rinderpest vaccine is a suitable immunogen for the protection of goats against peste des petits ruminants. PMID- 8460263 TI - Physicochemical alterations in blood, cerebrospinal fluid and urine in experimental lactic acidosis in sheep. AB - Ruminal acidosis was induced in six adult sheep by oral feeding of wheat grain at 90 g kg-1 body-weight. Ruminal fluid, blood, cerebrospinal fluid (CSF) and urine samples were collected before grain feeding (0 h) and thereafter at 12, 24, 48, 72, 96 and 120 hour intervals. Decrease in the rumen pH was associated with decreased pH in blood, CSF and urine and increased total lactic acid concentrations in rumen liquor, blood, CSF and urine. Significantly (P < 0.05) increased levels of sodium, inorganic phosphorus and decreased levels of potassium and calcium were observed in the serum of acidotic sheep. CSF analysis revealed decreased potassium and chloride levels and increased glucose concentration and total leucocyte count within 12 hours of the grain feeding. Pandy's test was positive in half of the surviving sheep at 12 hours and in all the sheep at 96 and 120 hours of observation. In urine, sodium and chloride levels decreased while potassium and inorganic phosphorus increased. The changes in the biochemical parameters started within 12 hours and lasted up to 48 to 120 hours of the observation period. PMID- 8460264 TI - Experimental intramammary infection of ewes with Staphylococcus aureus subsp anaerobius. AB - The susceptibility of the ovine mammary gland to experimental infection with Staphylococcus aureus subsp anaerobius was studied in five lactating Churra ewes. The left mammary gland of each ewe was inoculated with bacteria while the right halves remained untreated and served as a control. A rapid cellular response was elicited in all inoculated glands. The reaction of inoculated mammary glands varied from that of clinical mastitis (ewes C and D) to subclinical mastitis (ewes B and E) or merely to a transient increase of somatic cell counts (ewe A). S aureus subsp anaerobius is less pathogenic for ewes by the intramammary route than S aureus since doses of about 10(8) bacteria caused clinical mastitis in only two of the inoculated animals. PMID- 8460265 TI - Carrier erythrocytes from white-tailed deer: morphology, osmotic fragility and survival of circulating sickled erythrocytes. AB - Carrier erythrocytes are used to disseminate drugs in the circulatory system of animals. Carrier erythrocytes prepared from white-tailed deer (Odocoileus virginianus) do not circulate well in vivo. Although carrier cells were prepared from sickle and non-sickle cells with no apparent differences, their 24-hour survival was only 10 per cent. Osmotic fragility of carrier cells was increased over that of normal deer erythrocytes. Unlike erythrocytes from other ruminants, deer carrier erythrocytes are extremely fragile. Scanning electron micrographs of deer erythrocytes (sickle or non-sickle) in different stages of carrier cell preparation revealed no morphological differences. These data suggest that carrier cells from deer would not be amenable for use in long-term dissemination of drugs. PMID- 8460266 TI - ADP induces desensitisation of equine platelet aggregation responses: studies using ADP beta S, a stable analogue of ADP. AB - Pre-incubation of equine platelets in platelet-rich plasma with adenosine 5' diphosphate (ADP) induced a reduction in aggregation responsiveness to subsequent additions of ADP. The desensitisation was shown to be homologous since the responsiveness to platelet-activating factor, thrombin, collagen, 5 hydroxytryptamine or ionomycin remained unchanged. Adenosine 5'-(beta-thio) diphosphate (ADP beta S), a non-hydrolysable analogue of ADP, was shown to act as an agonist inducing aggregation by interaction with the ADP receptor. ADP beta S was then used in the desensitisation studies in which residual ADP was degraded by the addition of apyrase. The desensitisation to ADP beta S fully recovered by one hour after pre-treatment with ADP and was not induced by an extracellular mediator. The mechanism of desensitisation is therefore likely to involve the ADP receptor or proximal intermediates in the signal transduction pathway for ADP. PMID- 8460267 TI - The same fractions of Haemonchus contortus soluble antigen induce lymphocyte responses in naive lambs and immune sheep. AB - Soluble antigen extracted from third stage larvae of Haemonchus contortus was divided into fractions based on molecular weight by sodium dodecyl sulphate polyacrylamide gel electrophoresis and electrotransferred to nitrocellulose. Infection immunised adult sheep and H contortus naive lambs were used to examine the lymphocyte responses to these fractions in vitro. The results demonstrate that the same two fractions induced the strongest responses in both groups of animals. PMID- 8460268 TI - Distribution of antigens of Fasciola gigantica at various stages of development. AB - An indirect immunofluorescent antibody test on the serum of a Fasciola gigantica infected rabbit, showed specific fluorescence on the tegumental surface of miracidia, sporocysts, rediae, cercariae, metacercariae and juvenile worms aged between one and seven weeks. The same reaction occurred in the gut cells of cercariae and metacercariae and in the gut caeca of juveniles in the liver. The results of the absorption test indicated that stage-specific antigen(s) in metacercariae and seven-week-old worms existed mainly in the gut cells and the gut caeca, respectively. The precipitating antibody reacting to metacercariae antigens occurred at a very early stage of infection, but the titre dropped much earlier than that against the juvenile antigen. PMID- 8460269 TI - Eosinophilic synovitis following the intra-articular injection of bacterial antigen in horses. AB - Purified streptococcal M protein was injected into one intercarpal joint in three horses hyperimmunised with Streptococcus equi M protein vaccine. The contralateral joints were injected with pH adjusted polyionic solution. All antigen-injected joints developed a severe suppurative synovitis (mean synovial fluid nucleated cell count = 102,200 x 10(6) cells litre-1). Eosinophils were found in the synovial fluid and in synovial membrane biopsy specimens of two of the horses. Immune complexes were not demonstrated in the synovial membrane. Two horses are described that developed synovial fluid eosinophilia after the intra articular injection of streptococcal antigen. PMID- 8460270 TI - Hypobiosis of Trichostrongylus tenuis in experimentally infected grey partridges. AB - Storage of infective larvae (L3) of Trichostrongylus tenuis at +4 degrees C for six weeks before being given as single infections to grey partridges (Perdix perdix) did not increase the proportion of worms subsequently found to be hypobiotic. However, after repeated infections, hypobiotic larvae were numerous. Three infections given over three weeks resulted not only in the presence of many hypobiotic larvae, but also in the coincident loss of most adult worms. This indication of the role of immunity in the production of hypobiosis in grey partridges suggests that this species is not a good model for trichostrongylosis in red grouse (Lagopus lagopus scoticus). PMID- 8460271 TI - Haematological reference values for east African wild ungulates. AB - Basic haematological values were obtained in the field from shot, clinically normal, wild East African ungulates. The species studied were: Thomson's gazelle (Gazella thomsonii), Grant's gazelle (Gazella grantii), blue wildebeest (Conochaetes taurinus), Coke's hartebeest (Alcelaphus buselaphus cokii), impala (Aepyceros melampus) and Burchell's zebra (Equus burchelli). Red cell parameters compared well with previous reports although the mean cell haemoglobin concentrations were higher. The white cell counts were considerably lower in all species. The red and white cells of all species studied had standard mammalian morphology. Generally, the field equipment used worked well under the conditions encountered, although the field microscope made cell counting troublesome and the heat made the preservation of fixed slides difficult. PMID- 8460272 TI - Erysipelothrix tonsillarum isolated from dogs with endocarditis in Belgium. AB - Five strains of Erysipelothrix tonsillarum were isolated from dogs with endocarditis in Belgium. The identity and validity of the species was proved by serotyping, and biochemical and pathogenicity tests. All the isolates belonged to serovar 7 (E tonsillarum serovars); they produced acid from saccharose but did not induce any clinical sign of erysipelas in swine. These results suggest that some strains of E tonsillarum are a canine pathogen. PMID- 8460273 TI - Needle drainage of subretinal fluid. A randomized clinical trial. AB - Needle drainage of subretinal fluid with simultaneous observation using the indirect ophthalmoscope has been reported to have a very low complication rate. The technique was evaluated by a prospective clinical trial. The study group consisted of 100 patients undergoing scleral buckling for rhegmatogenous retinal detachment who were randomly assigned to groups treated with needle drainage or conventional two-stage drainage. At 1 month, the retina was anatomically flat in 88% of all cases. Subretinal hemorrhage occurred in 10 of 45 patients (22.2%) after needle drainage and in 7 of 55 patients (12.7%) after conventional drainage. The difference was not statistically significant. Retinal puncture occurred during conventional drainage in one case and in no cases during needle drainage. There were no cases of retinal incarceration. The results showed that subretinal hemorrhage was more common after needle drainage, but a larger study would be required to show whether this difference was statistically significant. The fear that the retina would be damaged by placement of a needle in the subretinal space throughout the drainage procedure was unfounded. PMID- 8460274 TI - Recognition of posterior scleritis and its treatment with indomethacin. AB - Posterior scleritis is a rare disease, the clinical signs of which may vary. There is no consensus on the appropriate method of treatment for this disease. Some have advocated treatment with nonsteroidal antiinflammatory drugs, whereas others have reported variable success with potentially more toxic therapy. Patients with posterior scleritis constitute approximately 1% of the uveitis clinic population at the Casey Eye Institute in Portland, Oregon. The cases of 6 patients with posterior scleritis, the diagnosis of which was elusive, are reported. Posterior scleritis was generally confirmed by ultrasound examination. Each of the patients responded to treatment with indomethacin, which was usually the sole method of nontopical therapy. Thus, recognition of this relatively rare disease had marked implications for treatment. PMID- 8460275 TI - Case report: associated retinal neovascularization and choroidal hemangioma. AB - Choroidal hemangiomas are vascular hamartomas that may be associated with secondary changes. Although subretinal fluid and associated neurosensory retina and retinal pigment epithelial changes are well documented, two cases in which retinal neovascularization was felt to be secondary to choroidal hemangiomas are presented. Long term follow-up reveals mild changes of the retinal neovascularization in both cases. The neovascularization did not affect the visual prognosis of the involved eyes. PMID- 8460276 TI - Pseudohypopyon in unilateral acute idiopathic maculopathy. AB - Unilateral acute idiopathic maculopathy (UAIM) is a recently described condition in young adults consisting of rapidly progressive central visual loss, gray-white opacification of the outer retina, and serous detachment of the macula. Bull's eye pattern pigmentary changes may occur in the macula after resolution of the acute phase of the disease. A case of UAIM in which a shifting of subretinal inflammatory infiltrate was observed is reported. This is the tenth reported case of UAIM, and represents a variation in the clinical presentation of this disease. The appearance and the shifting of the subretinal infiltrate seen in this patient support an inflammatory etiology of UAIM. PMID- 8460277 TI - Scanning laser densitometry in multiple evanescent white dot syndrome. AB - A 28-year-old man with multiple evanescent white dot syndrome (MEWDS) in the left eye was examined with a scanning laser densitometer. The first measurements were taken in the acute stage, and repeat examinations were performed during the process of recovery. Fundus pictures were obtained from a 20 degrees retinal field, in dark and light adapted stages. From these images visual pigment density maps were derived. In the acute stage of the disease, maps revealed small round areas of absent visual pigment, which did not always correspond with the visible white dots. The areas of absent visual pigment density were also larger than the white dots seen on funduscopic examination. Single spot densitometry at the fovea was also performed and showed no significant density difference of the foveal cones. Rod density difference measured at a locus 16 degrees in the temporal retina was much lower than normal with an increased time constant of rhodopsin regeneration. Ten weeks after the onset of the disease, no white dot lesions were visible on funduscopic examination. Rod density difference and regeneration time had become normal again, but with scanning laser densitometry the abnormal areas of no pigment were still faintly visible. It is concluded that these findings, completed with data of electroretinography, anomaloscopic testing, and perimetry, are in agreement with a metabolic disturbance at the level of the retinal pigment epithelium-photoreceptor complex. PMID- 8460278 TI - Diagnosis of occult subretinal neovascularization in age-related macular degeneration by infrared scanning laser videoangiography. AB - 180 consecutive patients with exudative age-related macular degeneration and clinical signs of subretinal neovascular membranes were examined by scanning laser fluorescein angiography. This technique demonstrated well-defined, newly formed subretinal vessels in approximately 50%, ill-defined subretinal vessels in approximately 20%, and not visible or occult subretinal vessels in the remaining 30% of the patients. Patients with ill-defined or occult neovascular membranes were also examined with scanning laser infrared angiography with cardiogreen. Newly formed subretinal vessels were well defined in approximately 40% of these patients, and ill defined in 23%. In 37% of the patients, neovascularizations were also not visible with infrared angiography. Results of scanning laser infrared angiography seem to be superior to earlier methods of infrared angiography. Conditions are discussed under which fluorescein and cardiogreen angiography can demonstrate subretinal membranes in age-related maculopathy. PMID- 8460280 TI - An ultrastructural study of the retina in human late infantile neuroaxonal dystrophy. AB - A case involving a girl who died at 11 years of age and who had developed normally until the age of 18 months, at which time further psychomotor maturation stopped and then regressed, is reported. The patient appeared hypotonic and showed loss of deep tendon reflexes, as well as bulbar signs and increasing immobility. Visual impairment resulted in blindness at the age of 7 years. Her disease was diagnosed as late infantile neuroaxonal dystrophy (LINAD) after examination of sural nerve biopsy samples and after autopsy. Under electron microscopy, retinal axons were filled with tubulocisternal profiles and occasional large lamellar clefts close to or distant from synaptic complexes. These lesions, typical of LINAD, were largely found in interior layers of the retina rather than in outer ones. As photoreceptors were preserved and their synaptic contacts within the outer nuclear layer appeared somewhat intact, blindness in LINAD is of the neuronal type, possibly all along the pathway from the bipolar retinal layer to the striate cortex. The findings also indicate that only particular types of axons or synaptic complexes may be involved in LINAD, and that the formation of lesions characteristic of LINAD is not ubiquitous within the retina. The cause for this selective involvement of retinal structures in LINAD remains to be resolved. PMID- 8460279 TI - Toxoplasma gondii retinochoroiditis after liver transplantation. AB - A 48-year-old woman with a previous a liver transplant and a cataract extraction developed a necrotizing retinochoroiditis in her right eye. Vitreous and serum cultures failed to yield a causative organism. As the retinochoroiditis progressed, visual acuity worsened to the point of no light perception, and the eye became blind and painful. An enucleation was performed and histologic examination showed Toxoplasma gondii necrotizing retinochoroiditis. This is the first histologically documented case of T. gondii retinochoroiditis after liver transplantation. The fulminant clinicopathologic appearance of the retinochoroiditis is similar to that previously reported to occur in acquired immune deficiency syndrome (AIDS) and other forms of immunosuppression, unlike the reactivated congenital retinochoroiditis that occurs in immunocompetent patients. PMID- 8460281 TI - Retinal tolerance to intravitreal perfluoroethylcyclohexane liquid in the rabbit. AB - To evaluate the use of perfluoroethylcyclohexane (PFE) liquid during vitreoretinal surgery, retinal tolerance was tested by electroretinographic (ERG) and histologic study of rabbit eyes undergoing intravitreal placement of PFE for 48 hours. When PFE occupied the vitreous cavity, ERG amplitudes were decreased, probably because of electrical insulation by the liquid. Immediately after removal of the liquid, elevations of a and b waves occurred. Further improvements in the waveforms were recorded when tested between 5 days and 2 months after PFE removal, such that the eyes injected with PFE exhibited ERG amplitudes comparable to contralateral control eyes and preoperative eyes. Histologic examination of the eyes 2 months after PFE removal also revealed normal morphologic features. Small residual amounts of PFE produced no adverse histologic changes after 6 months. When PFE remained intravitreally for longer than 1 week, dispersion of the liquid and preretinal accumulation of macrophages occurred, and in inferior retina, distortions of photoreceptor outer segments and narrowing of outer plexiform layer were observed in the rabbit model. PMID- 8460282 TI - A phantom system for microwave treatment of intraocular tumors. AB - A gel-block system was developed to illustrate heating patterns induced by ophthalmic microwave applicators. A heat-sensitive liquid crystal card was affixed as to bisect a Lucite box. The box was then filled with a clear tissue equivalent polyacrylamide gel. It was found that semicircular heating patterns were generated within the gel. These patterns were visualized by placing one of the dish-shaped ophthalmic microwave applicators on top of the polyacrylamide gel and the heat-sensitive liquid crystal card. An antenna was then placed in the gel and behind the card. Microwave energy was sent through the card and into the gel. This demonstrated the relatively homogeneous and roughly circular heating pattern produced at the applicator's surface. A combination of these profiles led to construction of a three-dimensional, dome-shaped model of heating, as provided by this microwave antenna design. PMID- 8460283 TI - Measurement of ocular tumor volumes from serial, cross-sectional ultrasound scans. AB - A system has been developed to determine intraocular tumor volume, a characteristic that has been estimated in previous studies from linear dimensions using a variety of models. Volume was determined by tracing tumor boundaries in sequential, parallel ultrasound scans, adding the areas and multiplying by the interslice interval. The in vitro accuracy of the technique was within +/- 2%. The mean difference between volumes determined from replicate in vivo scans of intraocular tumors was 4.3%. Serial scan volumes were, on average, 19% smaller than volumes computed from an ellipsoidal model and 13% smaller than area rotational volumes. Differences of as much as 50% were observed between serial scan volumes and volumes computed with these models. The results indicate that methods based on either linear measurements or the tumor area in a single cross section will tend to both systematically overestimate tumor volume and suffer from unpredictable, nonsystematic errors. PMID- 8460284 TI - Pneumatic retinopexy using only air. AB - Pneumatic retinopexy was performed using only air in an attempt to minimize vitreous disturbance and lower the incidence of postoperative proliferative vitreoretinopathy (PVR) and premacular membranes (PMM). Retinal cryopexy or laser treatment (in 2 cases) and intravitreal injection of 0.8 cc filtered air were performed on 45 rhegmatogenous retinal detachments with superior breaks and no preoperative vitreous hemorrhage or PVR. Reattachment was achieved in 39 (86.7%) eyes. The remaining 6 eyes were secondarily treated with scleral buckle surgery, which was successful in all cases. The average length of follow-up was 17.1 +/- 8.6 months, at which time visual acuity was the same or better in 44 (97.8%) eyes. In 1 case (2.2%) PVR developed, a PMM formed in 1 case (2.2%), and new or missed retinal breaks were found in 4 cases (8.8%). This technique achieves a high rate of reattachment, good visual outcome, and low incidence of PVR, PMM, and new or missed breaks, perhaps due to the short-acting, nonexpansile nature of air. PMID- 8460285 TI - Long-term storage of perfluoropropane (C3F8) in plastic syringes. PMID- 8460286 TI - Adenosine and the adaptation to exercise. PMID- 8460287 TI - Perceived exertion. Antecedents and applications. AB - The field of perceived exertion has largely concerned itself with the problem of identifying the primary antecedents to this psychophysiological phenomenon. A vast literature has evolved addressing this problem, but it is fraught with contradictions. At this stage a comprehensive theory of perceived exertion does not exist. It is generally accepted that perception of exertion is dominated by physiological determinants. Physiological sensory cues have been separated into 2 categories: local factors (sensations from the working muscles and joints), and central factors (sensations from the cardiopulmonary system). Major reviews in this area generally agree that local factors dominate perception of exertion. Recent work in perceived exertion has placed an emphasis on examining the contributing psychological factors. Research into the psychological factors affecting perceived exertion has been highly fragmented with no apparent theoretical framework as a base. At the same time it is clear that an integration of psychological and physiological variables is required to obtain theoretically meaningful knowledge of this multidimensional construct. The assumed dominance of physiological factors has been challenged by the contention that in field situations, in which a variety of social psychological influences operate, psychological determinants of perceived exertion may be vastly more influential than previously estimated. Identification of the primary determinants of perceived exertion and knowledge of how these factors are integrated is vital for a concrete theory of perceived exertion to evolve. PMID- 8460290 TI - Common sports hand injuries. An overview of aetiology, management and prevention. AB - Injuries to the hand are among the most common in all of sports. Appropriate care should include prompt diagnosis and treatment. Dislocations of the digits should be reduced promptly, particularly the carpometacarpal joint of the thumb. Volar dislocations of the proximal interphalangeal joint need to be splinted in full extension, and the more common dorsal dislocations in slight flexion. Collateral ligament injuries of the fingers respond well to initial immobilisation followed by early motion. Although ligament injuries to the thumb metacarpophalangeal joint may be treated closed, they generally respond better to operative management. This is true particularly for those occurring on the ulnar side which are at risk for soft tissue interposition. Metacarpal shaft fractures can usually be treated closed with acceptance of more significant deformity in the ulnar 2 shafts. Open reduction is reserved for multiple shaft fractures and deformity in the second and third metacarpals. Near-perfect alignment should be the goal in extra-articular fractures of the phalanges as well as fractures involving the articular surface. Closed tendon injuries occurring on the extensor side, i.e. mallet finger, may be treated with prolonged splinting if a congruous reduction can be achieved with closed reduction. Flexor side avulsions occurring most commonly in the ring finger also require prompt attention with the level of retraction of the tendon dictating the need for the immediacy of repair. Although often not initially debilitating, lack of recognition of hand injuries and improper treatment can lead to debilitating sequelae. Therefore, early recognition and diagnosis can easily avoid many of the pitfalls of care resulting in a less than optimal outcome. PMID- 8460291 TI - [What is your diagnosis? Discoid lupus erythematosus (DLE)]. PMID- 8460288 TI - Is the gut an athletic organ? Digestion, absorption and exercise. AB - Digestion is a process which takes place in resting conditions. Exercise is characterised by a shift in blood flow away from the gastrointestinal (GI) tract towards the active muscle and the lungs. Changes in nervous activity, in circulating hormones, peptides and metabolic end products lead to changes in GI motility, blood flow, absorption and secretion. In exhausting endurance events, 30 to 50% of participants may suffer from 1 or more GI symptoms, which have often been interpreted as being a result of maldigestion, malabsorption, changes in small intestinal transit, and improper food and fluid intake. Results of field and laboratory studies show that pre-exercise ingestion of foods rich in dietary fibre, fat and protein, as well as strongly hypertonic drinks, may cause upper GI symptoms such as stomach ache, vomiting and reflux or heartburn. There is no evidence that the ingestion of nonhypertonic drinks during exercise induces GI distress and diarrhoea. In contrast, dehydration because of insufficient fluid replacement has been shown to increase the frequency of GI symptoms. Lower GI symptoms, such as intestinal cramps, diarrhoea--sometimes bloody--and urge to defecate seem to be more related to changes in gut motility and tone, as well as a secretion. These symptoms are to a large extent induced by the degree of decrease in GI blood flow and the secretion of secretory substances such as vasoactive intestinal peptide, secretin and peptide-histidine-methionine. Intensive exercise causes considerable reflux, delays small intestinal transit, reduces absorption and tends to increase colonic transit. The latter may reduce whole gut transit time. The gut is not an athletic organ in the sense that it adapts to increased exercise-induced physiological stress. However, adequate training leads to a less dramatic decrease of GI blood flow at submaximal exercise intensities and is important in the prevention of GI symptoms. PMID- 8460292 TI - [Pumps and access ports in the drug therapy of pain]. AB - Advances in the technology of infusion pumps and ports have opened a new spectrum of indications. The choice of the device is dependent on the specific indication. The PCA concept (patient-controlled analgesia) has made a more individualized pain therapy possible. Recent developments are aimed at substituting the individual on-demand bolus with adaptations in steady-state serum concentrations of analgesics using BET (bolus-elimination transfer) programming. As demonstrated in several studies, ports can be safely used for chronic pain treatment. However, as with the use of infusion pumps, the indications for use must be evaluated carefully and especially-trained staff is a prerequisite for success. PMID- 8460293 TI - [Compliance problems and behavioral medicine implications in the drug therapy of pain]. AB - Many patients, even cancer patients do not take their medication at all or at the prescribed dose showing thus a form of noncompliance. Reasons for this are manyfold and differ from patient to patient. They may undergo dynamic changes in the course of disease. Experience shows, that compliance is mainly improved when patients have the impression to be responsible for their comportment. This is an important goal in therapy of patients with chronic pain. Of particular importance is therefore the doctor-patient relation, i.e. non-compliance thus always indicates a disturbed doctor-patient relation. PMID- 8460289 TI - Exercise in the prevention and treatment of cancer. An update. AB - Physical activity potentially encourages a healthy lifestyle and it could have a more direct preventive effect on certain forms of carcinogenesis (for instance, by speeding gastrointestinal transit, or by moderating sex hormone levels). However, there are also potential negative effects, particularly an excessive exposure to ultraviolet light in certain water sports. The many types of neoplasm and the equally varied sources of physical activity militate against finding any simple relationship between the risk of malignancy and the individual's physical activity history. Nevertheless, evidence that physical activity protects against certain forms of cancer can be deduced from studies of experimental animals, former athletes, people employed in active occupations, and those with an active recreational lifestyle. Many occupational surveys and a number of studies of recreational activity show an association between sedentary living and a risk of colon cancer, both in men and in women. Moreover, an application of Bradford Hill's criteria gives some support to the causal nature of the association. More limited data suggest that a history of active leisure is associated with a reduced risk of all-cause cancer and in women of breast and reproductive system cancers. The last observation must still be reconciled with an apparent increase in the risk of prostatic cancer in active men. Since moderate exercise elevates mood and helps to conserve lean tissue, it may finally be a helpful component of treatment after a neoplasm has been diagnosed. PMID- 8460294 TI - [Risk-benefit considerations in the drug therapy of chronic tumor-related pain]. AB - Cost and risk assessment in medicine requires evaluation of objective and subjective parameters. Objectively correct medicamentous treatment of chronic pain is cost-effective, above all by reducing expensive hospitalization. The greatest benefit for the patient comes from improved quality of life and increased independence and mobility. Side effects of drugs are inevitable but can be controlled successfully in most instances. PMID- 8460295 TI - Planning for future stability and growth. PMID- 8460296 TI - Appraisal: staff development tool or bureaucratic nightmare? PMID- 8460297 TI - The nurse's role in purchasing. PMID- 8460298 TI - Levels of nurse staffing. PMID- 8460299 TI - Pay and performance. PMID- 8460301 TI - Team and primary nursing: a reply. PMID- 8460300 TI - Purchasing for health gain. PMID- 8460302 TI - Auditing clinical placements. AB - The auditing of clinical areas is an important aspect of evaluating and maintaining standards in the Project 2000 scheme of nurse education. The auditing process brings many unexpected additional benefits, including increased ownership of the course and a developing sense of partnership between clinicians and educators. It is not an endeavour that should be undertaken lightly, and many problems can be prevented by good planning, which may include extensive piloting of the audit tool and process. PMID- 8460304 TI - Research in nursing, Part 2. PMID- 8460303 TI - Patient-teaching: a neglected area of nurse practice? PMID- 8460305 TI - Changing theory in nursing practice. PMID- 8460306 TI - The concept of the 'gaze' in mental health nursing. PMID- 8460307 TI - Responding to special needs. PMID- 8460308 TI - Career paths of nurse graduates. PMID- 8460309 TI - Project management. PMID- 8460310 TI - ["Nursing guidelines" ... again and always!]. PMID- 8460311 TI - [The image of the private practice nurse]. PMID- 8460312 TI - [Home care services since 1991]. PMID- 8460313 TI - [New ... a humidification filter for tracheostomies]. PMID- 8460314 TI - [The educational relationship: some preliminaries?]. PMID- 8460315 TI - [Allergies]. PMID- 8460316 TI - [Long term treatment of chronic obstructive bronchopneumopathies]. PMID- 8460317 TI - [Management of patients with HIV: a nurse witness. Interview by Isabelle Lefevre]. PMID- 8460318 TI - [Infection by HIV]. PMID- 8460319 TI - [Professional risk of infection by the human immunodeficiency virus]. PMID- 8460320 TI - [Risks of AIDS transmission in the surgical milieu]. PMID- 8460321 TI - [The risks of viral transmission by bone allografts]. PMID- 8460322 TI - [Digestive infections during AIDS, experience in Lyons with 81 patients]. PMID- 8460323 TI - [Information on AIDS in industries]. PMID- 8460324 TI - [The contribution of Public Assistance--Hospitals of Paris to the campaign against AIDS]. PMID- 8460325 TI - [Action of the cultural minister in the campaign against AIDS]. PMID- 8460327 TI - ["They need nurses..."]. PMID- 8460326 TI - [Dossier: AIDS. Organizations and associations]. PMID- 8460328 TI - [Hemolytic disease of newborns]. PMID- 8460329 TI - [Neurophysiology of eating behavior]. PMID- 8460330 TI - [Financing of AIDS prevention: serious warning from WHO]. PMID- 8460331 TI - [Hemoccult II]. PMID- 8460332 TI - Group B streptococcal meningitis in adults: case report and review of the literature. AB - A case of group B streptococcal meningitis in an adult is presented with a review of 42 other cases reported in the English literature since 1940. Their median age was 58 years (72.5% were older than 45 years). Male/female ratio was 0.9:1, with male predominance in patients older than 60 years (76.5%). Predisposing illnesses were common but 13.9% of cases reported had no identifiable risk factor. Encephalopathy and bacteremia were frequent (81.3% and 94.4% respectively) and many patients (30%) had other foci of infection. Gram stain of cerebrospinal fluid was positive in 75% of cases. Mortality was 18.4% and 9.7% of survivors had bilateral hearing loss. Thus, this review illustrates that group B streptococcal meningitis in adults is a rare disease which occurs among high risk individuals. It is characterized by frequent encephalopathy, prevalence of other foci of infection and bacteremia with an outcome similar to other types of purulent meningitides. PMID- 8460333 TI - Hyponatremia and adrenocortical function in patients with severe bacterial infections. AB - Hyponatremia occurs frequently in patients with severe infections though its cause has not been established. Recent studies have reported that in some patients with septicemia, adrenocortical insufficiency is present. To ascertain whether occurrence of hyponatremia and adrenocortical insufficiency might be related, we studied 40 patients with septicemia (11 in septic shock). A short corticotropin test was used for assessing the adrenocortical function. Though both adrenocortical failure (in 5 patients) and hyponatremia (serum sodium concentration < 125 mmol/l in 3 patients) occurred, there was no apparent relationship between the entities. PMID- 8460334 TI - The value of surveillance cultures in neutropenic patients receiving selective intestinal decontamination. AB - 230 neutropenic episodes in 84 patients with acute myeloid leukemia receiving selective intestinal decontamination were studied to evaluate the ability of surveillance cultures to monitor the efficacy of microbial suppression, to identify causative organisms in case of fever, and to predict infection due to potential pathogens (i.e. Staphylococcus aureus and aerobic Gram-negative bacteria). Most cultures became negative soon after the administration of prophylactic antibiotics and there were only few persistent colonizations. 14 potential pathogens resistant to the intestinal decontamination regimen were isolated in surveillance cultures, none of which caused infection. Of the 212 febrile episodes, only 22 were caused by a microbiologically documented infection with potential pathogens. Most microbiologically documented infections were caused by organisms not routinely identified by surveillance cultures, indicating efficient selective intestinal decontamination. Only 9 (41%) of the 22 infections with potential pathogens were predicted by surveillance cultures. We conclude that surveillance cultures are of limited use in predicting infection or identifying causative organisms of fever in neutropenic patients receiving selective intestinal decontamination. However, they are useful in monitoring the efficacy of microbial suppression. One set of surveillance cultures each week after the disappearance of potential pathogens would be sufficient. PMID- 8460335 TI - A new dosing regimen for metronidazole in malnourished children. AB - The use of metronidazole for the treatment of intestinal parasitosis has increased markedly, particularly in developing countries, where the association of malnutrition and parasitosis is very common. Since biotransformation of metronidazole is significantly affected by severe malnutrition, and undesirable effects of the drug seem to be related to its plasma concentration, it was decided to carry out a study to establish a dosing-regimen of metronidazole in severely malnourished children. A single dose of 30 mg/kg body weight, and computer simulation of a steady-state was studied in 10 malnourished and in 10 patients undergoing nutritional rehabilitation. Due to ethical considerations (refusal of parents to allow a second dose of metronidazole) acute malnourished children and rehabilitated patients are 2 distinct groups. The results indicate that a predicted drug cumulation would occur in malnourished children with the ordinary dosage regimen (30 mg/kg/day). Based on the clearance data, daily maintenance doses for pediatric patients with severe malnutrition should be 12.0 mg/kg/day, corresponding to a 60% reduction of the common dose calculated to achieve and maintain a plasma concentration of 6.0 micrograms/ml of metronidazole. The study illustrates the need for pharmacokinetic data to establish the individual dose of a drug particularly under conditions that alter biotransformation processes. PMID- 8460336 TI - Activity of erythromycin and clindamycin in an experimental Staphylococcus aureus infection in normal and granulocytopenic mice. A comparative in vivo and in vitro study. AB - The activity of 2 bacteriostatic antibiotics, erythromycin and clindamycin, against Staphylococcus aureus was studied in vitro and in an experimental infection in granulocytopenic as well as normal mice. In vivo, on the basis of dosage, erythromycin was 2.20 times more potent than clindamycin in normal mice and 1.95 times more potent in irradiated granulocytopenic mice. Tissue concentrations were calculated from the plasma concentrations, taking plasma protein and tissue binding into account. On the basis of the area under the curve for the free tissue concentrations, clindamycin was 1.48 times more potent than erythromycin in normal mice and 1.64 times more potent in irradiated mice, which is somewhat less than expected from the comparison in vitro. It is concluded that the relative antistaphylococcal efficacies of erythromycin and clindamycin in vivo can be predicted from the in-vitro values if the relevant pharmacokinetics are taken into account. Irradiation decreased the efficacy of both antibiotics such that an about 8-fold increase in dose led to an antibacterial effect similar to that in non-irradiated animals. This could imply that these drugs will not be sufficiently effective against staphylococcal infections in granulocytopenic patients. PMID- 8460337 TI - Interferon alpha-2b treatment in an HIV-infected patient with hepatitis B virus induced nephrotic syndrome. AB - A 31-year-old male patient with an asymptomatic HIV infection but with a hepatitis B (HBV) related membraneous glomerulonephritis with nephrotic syndrome was given interferon alpha-2b subcutaneously 3 times weekly for 7.5 months. Zidovudine was added at the 10th week due to low CD4+ cell counts. Before the 6th week of treatment the patient reported a reduced need for diuretics to keep his lower limb edemas at a minimum. This response was partially sustained even after the 7.5 months interferon treatment course. The titers of HBV-DNA decreased markedly during the treatment with interferon but rose to pretreatment levels after discontinuation of the interferon treatment. The serum albumin increased but the proteinuria and hematuria were unaffected. Adverse reactions like fever, myalgias and anemia were tolerable and did not require dose reduction of either interferon or zidovudine. This treatment regimen, at least temporarily, improved the situation for the patient and can be worthwhile to try in HIV-infected patients with HBV related nephritis with nephrotic syndrome. PMID- 8460338 TI - Septicaemia caused by an unusual Neisseria meningitidis species following dental extraction. AB - Dental procedures are frequently followed by transient bacteraemia. Bacteria obtained in the blood cultures are similar to bacteria of the normal mouth flora such as oral streptococci. The potential risk of bacteraemia following dental manipulations is infective endocarditis. We report here a rare case of septicaemia following dental extraction in a 84-year-old woman. Neisseria meningitidis group B type 1P1.9 was cultured from the blood. Postextraction septicaemia caused by meningococci has not been described before. Meningococcaemia as a rare complication of dental extraction is emphasized. PMID- 8460339 TI - Sexual acquisition of acute pyelonephritis in a man. AB - A 51-year-old man presented with acute cystitis at a time when his wife was admitted with symptoms of acute pyelonephritis. Before the man developed his symptoms his wife had complained of urinary frequency and dysuria for a 2-week period. Two weeks after a 10-day course with trimethoprim he experienced a relapse manifesting as acute febrile pyelonephritis. The strains of Escherichia coli isolated from the urine of both patients belonged to the same serotype O51, O117:K1, were non-haemolytic, produced aerobactin, expressed P-fimbriae, and showed identical antibiotic susceptibility pattern. The findings strongly suggest that the E. coli strain might have been sexually transmitted from the wife to her husband. PMID- 8460340 TI - Multiorgan involvement in systemic cat-scratch disease. AB - Cat-scratch disease is considered in the differential diagnosis of benign regional lymphadenopathy. We describe a case of cat-scratch disease in a 12-year old boy with multiple bony, hepatic and splenic lesions which resolved with chemotherapy. The present case with simultaneous multiorgan involvement supports the view of a systemic nature of the disease. PMID- 8460341 TI - Tuberculous subcutaneous abscesses developing during chemotherapy for pulmonary tuberculosis. AB - A 32-year-old woman with systemic lupus erythematosus developed military tuberculosis. Several subcutaneous abscesses infected with a strain of Mycobacterium tuberculosis susceptible to all antituberculosis drugs occurred successively during initial 1-4 months of regular antituberculosis therapy. The lung and skin lesions disappeared after continuous treatment. We emphasize that emergence of tuberculous skin lesions may occur during treatment but this does not necessarily indicate treatment failure. PMID- 8460342 TI - Nonfatal total expulsion of the distal oesophagus due to invasive candida oesophagitis. AB - Invasive fungal infection is an increasing problem in severely immunocompromised patients. A 30-year-old man with profound pancytopenia due to acute myelogenous leukaemia acquired a severe invasive candida oesophagitis with total desquamation and expulsion of 90 mm of the distal oesophagus. The case report lends support to the concept of early recognition of fungal oesophagitis including species identification and possibly also antimycotic prophylaxis during immunosuppressive treatment. PMID- 8460343 TI - Doxycycline and pyrimethamine for toxoplasmic encephalitis. AB - Clinical improvement is reported in a 40-year-old man with AIDS and presumed toxoplasmic encephalitis, who was treated with doxycycline, 400 mg, and pyrimethamine, 25 mg, daily. Computerised tomography (CT) scanning of the brain showed complete resolution of 2 ring-enhanced lesions within 5 weeks. PMID- 8460344 TI - Non-efficacy of low-dose intradermal vaccination against hepatitis B in Down's syndrome. AB - Persons with Down's syndrome (DS) constitute a risk group for hepatitis B (HB) and are recommended to be immunized. Of 123 persons with DS in Orebro county screened for markers of HB, 31% had such markers; 16% were potentially contagious. 83 persons without markers participated in a comparative trial of the immunogenicity of a recombinant HB vaccine given either intramuscularly (IM) or in a lower dose intradermally (ID). Immunity developed in 73% after IM vaccination as compared to 29% of those given ID vaccination (p < 0.005). At 3 year follow-up half and two-thirds of the immune persons, respectively, had lost their immunity. Those > 30 years had a poor immunization response compared to the younger ones (p < 0.01). Only 19% of the non-responders developed immunity after an IM booster dose given 10 months after the third injection. Intradermal vaccination is not warranted in persons with DS, especially not in middle aged and older persons. A booster dose of vaccine does not ascertain immunity in those who do not respond with immunity to the ordinary immunization schedule. Post vaccination immunity should therefore be controlled. PMID- 8460345 TI - DNA fingerprinting of serogroup A meningococci. PMID- 8460346 TI - Alpha-streptococci as supplementary treatment of recurrent streptococcal tonsillitis: a randomized placebo-controlled study. AB - Recurrences are a common finding after antibiotic treatment of acute group A streptococcal tonsillitis. This has been attributed to several factors, among others a disturbed normal throat flora and especially a lack of alpha streptococci. It thus seems logical in patients with recurrent streptococcal tonsillitis, to restore the normal alpha-streptococcal flora by reimplantation of alpha-streptococci. This was performed in a double blinded, randomized, placebo controlled study. 36 patients with recurrent streptococcal group A tonsillitis were treated with antibiotics followed by either placebo (19 patients) or a pool of 4 selected alpha-streptococcal strains (17 patients) with good interfering activity against clinical isolates of beta-streptococci. No patient recurred during the first 2 months of follow-up in the alpha-treated group, but 7 in those treated with antibiotics and placebo. After 3 months 1 in the patient group treated with antibiotics and alpha-streptococci and 11 in the placebo-treated group recurred. These results are statistically highly significant and show that recolonisation with alpha-streptococci seems to offer a new way to lower the rate of recurrence in streptococcal throat infections. PMID- 8460347 TI - In vitro effect on group A streptococci of loracarbef versus cefadroxil, cefaclor and penicillin V. AB - The in vitro activity of loracarbef, penicillin V, cefaclor and cefadroxil against log and stationary phase cultures of group A streptococci was compared. MICs and MBCs were determined with the broth dilution method and by a modified agar plate dilution technique where the beta-lactams were inactivated after the MICs were determined allowing inhibited but not killed organisms to grow on further incubation. The MICs of loracarbef and the two cephalosporins were 16-32 times higher than those of penicillin V. In plate dilution the MBC/MIC ratios of all agents were < or = 2 for log phase cultures. With stationary phase cultures, especially in the broth dilution test, the MBC/MIC ratios of loracarbef and the two cephalosporins were > or = 32 for a large number of strains. The phenotype response of stationary phase cultures to beta-lactam antibiotics may not only be related to the physiological status of the streptococci, to the culture conditions and to the beta-lactam under test. The present investigation indicated that the phenotypic response was also an intrinsic property of certain strains. PMID- 8460348 TI - Failure of clindamycin to influence the course of severe oromucositis associated with streptococcal bacteraemia in allogeneic bone marrow transplant recipients. AB - 33 consecutive allogeneic bone marrow transplant recipients who were likely to develop streptococcal bacteraemia were treated for 5 days with clindamycin (900 mg i.v. t.d.s) and ceftazidime (2 g t.d.s.) for the initial management of fever associated with severe oral mucositis. Bacteraemia due to 'viridans' streptococci was encountered in 23 cases (70%) as mucositis progressed to peak severity and occurred a day before fever in 8 cases. At the end of treatment with clindamycin only 2 patients had defervesced although the streptococci were successfully eradicated. C-reactive protein (CRP) levels continued to rise in 18 cases and declined by more than 10% in only 7 cases. Severe oromucositis rather than infection appeared to induce an acute phase response with fever suggesting bacteraemia due to 'viridans' streptococci to have been a consequence of mucosal damage. Indeed, oromucositis was the only primary focus of inflammation in 22 patients and only after its resolution did both fever and CRP levels diminish. By then, patients had also begun to recover from granulocytopenia. These data indicate that rather than including a specific antimicrobial like clindamycin in an empirical regimen, it would be more beneficial to evolve strategies that minimise mucosal damage in this patient population. PMID- 8460349 TI - The role of antigen detection in pneumococcal carriers: a comparison between cultures and capsular antigen detection in upper respiratory tract secretions. AB - During the winter season upper respiratory tract secretions from 166 patients with stable chronic obstructive pulmonary disease (COPD) or asthma were simultaneously cultured for Streptococcus pneumoniae and tested for pneumococcal capsular antigen. Latex agglutination was employed to investigate the effect of pneumococcal carriership on pneumococcal capsular antigen detection in upper respiratory tract secretions. All specimens originating from the oropharynx, nasopharynx and saliva were both cultured and investigated in parallel for the presence of antigen. The recovery of pneumococci from the different areas was unequally distributed (oropharynx 29%, nasopharynx 8%, and saliva 16%), with the highest isolation rate from the oropharynx alone. Only 4 (3%) of the oropharyngeal swabs, 1 (1%) of the nasopharyngeal swabs and 14 (9%) of the saliva specimens yielded both pneumococcal antigen and a positive culture for S. pneumoniae. A further 9 (6%) of the oropharyngeal swabs, 5 (3%) of the nasopharyngeal swabs, and 50 (33%) of the saliva specimens were antigen positive only, with no pneumococci isolated on culture. It is speculated that these reactions were due to cross-reacting microorganisms (especially alpha-haemolytic streptococci) present in saliva and contaminating the oropharynx and the nasopharynx. Quantitative cultures of 9 oropharyngeal swabs yielded S. pneumoniae in concentrations too low to be detectable by latex agglutination. The study indicates that there is a poor relation between pneumococcal colonization and antigen detection in the oropharynx and nasopharynx. Antigen present in these secretions is probably not an important disrupting factor by contamination when detecting pneumococcal antigen in washed sputum. The false positive antigen results in saliva are probably due to cross-reactions with alpha-haemolytic streptococci. PMID- 8460350 TI - The origin of Staphylococcus saprophyticus from cattle and pigs. AB - Staphylococcus saprophyticus is a common cause of urinary tract infections. We have earlier shown that the bacterium is a contaminant of food of animal origin. In order to trace the natural reservoir of the bacterium, samples were taken from farming environment and from slaughtered carcasses. S. saprophyticus was found in 7.1% of rectal swabs from cattle carcasses and in 7.3% of rectal swabs from slaughtered pigs. The seasonal variation of these isolates paralleled the seasonality of urinary tract infections due to the same bacterium. S. saprophyticus was also isolated in 1.1% of rectal swabs from living cows, in 1.6% from pasture grass and from 12.4% of various indoor fodder. The fodder presented a seasonal distribution with a peak incidence of S. saprophyticus some months earlier than in rectal swabs. The bacterium was especially frequent in samples of fodder taken from the managers. S. saprophyticus is most likely a bacterium with a zoonotic origin. PMID- 8460351 TI - Successful interferon-gamma therapy in a chronic granulomatous disease (CGD) patient suffering from Staphylococcus aureus hepatic abscess and invasive Candida albicans infection. AB - A 16-year old boy with an early history of recurrent lower respiratory tract infections exhibited symptoms of prolonged septic fever and liver abscess. Cultures from liver puncture were positive for Staphylococcus aureus, and the patient initially responded to antibacterial therapy. After a period of 4 months, however, the infection relapsed, and further treatment with broad antibacterial, antifungal and tuberculostatic drugs was ineffective. Neither soluble nor particulate stimuli were found to elicit the respiratory burst response in granulocytes from the patient. Spectral analysis of granulocyte cytochrome-b confirmed the diagnosis of chronic granulomatous disease. Since the patient's physical condition deteriorated severely during the prolonged (10-week) septic course, immunosupportive interferon-gamma was added to the anti-microbial therapy. With this regime, the fever subsided and the general condition of the patient improved dramatically. He could be discharged from hospital 9 weeks after the introduction of interferon-gamma and was, at an elective follow-up control 1 month later, convalescing and showed no signs of active infection. PMID- 8460352 TI - Tick-borne borreliosis in the archipelago of southern Sweden. AB - Sera from 480 individuals living on an island at the Baltic coast in southern Sweden were tested by ELISA for detection of antibodies against Borrelia burgdorferi. The area was found to be highly endemic for Lyme borreliosis with elevated IgG antibody levels in 90/480 individuals (19%). Of 149 ticks collected on the island 16 nymphs (17%) and 15 adults (26%) were infected by B. burgdorferi. The occurrence of antibodies to B. burgdorferi increased with age and time spent in the endemic area. Infection without manifest disease seemed to dominate since only 18/480 (4%), or 6/90 (7%) with positive serology, had been treated for Lyme borreliosis. However, the prevalence of symptoms associated with late manifestations of Lyme borreliosis e.g. arthralgia, chronic skin efflorescences or neurologic disorders was significantly higher among seropositive compared to seronegative individuals. PMID- 8460353 TI - Prevalence of hepatitis B virus markers among intravenous drug abusers in Stockholm: impact of heterosexual transmission. AB - In order to study the importance of sexual transmission of hepatitis B virus (HBV) among intravenous drug abusers (IVDAs), and from IVDAs to others, we consecutively interviewed 171 IVDAs detained at the Stockholm Remand Prison during 4 months in 1990. Sexual histories revealed that 77% reported > or = 3 sexual partners during the last 3 years, 64% had had a sexual partner who did not inject drugs, and 61% reported a prior STD. The prevalence of HBV markers was 75%. In a multiple logistic regression analysis, a high risk for HBV markers was associated with an increasing duration of drug abuse, a high prevalence of hepatitis A markers, and an increasing number of drug injecting sexual partners during the last 3 years, indicating that sexual transmission, along with sharing of needles, may contribute to the high prevalence of HBV markers within this group. It is suggested that an adequate sexual history must be obtained from IVDAs with acute viral hepatitis in order to identify sexual partners who should be offered postexposure prophylaxis, and that non-immune IVDAs should be vaccinated against viral hepatitis A and B. PMID- 8460354 TI - The treatment of Pseudomonas aeruginosa meningitis--old regime or newer drugs? AB - Currently intravenous ceftazidime with or without an aminoglycoside or alternatively ciprofloxacin are the recommended antibiotics of choice in Pseudomonas aeruginosa meningitis. A case of atraumatic, spontaneous Ps. aeruginosa meningitis in a child with acute lymphoblastic leukaemia is described. Despite the organism demonstrating in vitro sensitivity to ceftazidime, netilmicin and ciprofloxacin, intravenous therapy with these drugs failed to sterilise the cerebrospinal fluid (CSF). Both netilmicin and ciprofloxacin failed to attain therapeutic levels in the CSF. Intrathecal aminoglycoside therapy via an intraventricular reservoir was successful in eradicating the infection. In children with meningitis due to Ps. aeruginosa where intravenous therapy is unsuccessful despite in vitro sensitivity to recommended antibiotics; intraventricular medications should be commenced as soon as possible. PMID- 8460355 TI - The significance of polymicrobial growth in urine: contamination or true infection. AB - Urine growing more than one organism is usually considered contaminated. During 1980-1984, among 198 episodes of urosepsis with at least one identical organism in blood and urine, there were 62 with polymicrobial growth from urine. The significance of the multiple growth from urine was confirmed in 12 episodes by the growth of more than one identical organism in blood and urine and in 21 episodes by repeated growth of the same mixture of organisms in multiple urine specimens. Escherichia coli had a higher tendency to invade blood stream than other Gram-negative organisms, such as pseudomonas and proteus. In specific populations with high risk of polymicrobial infection, multiple growth in urine should be carefully evaluated with appropriate colony count and identification of each isolate. PMID- 8460356 TI - Association of pneumonia and lung cancer: the value of convalescent chest radiography and follow-up. AB - A retrospective study of 1011 hospitalized patients with pneumonia was undertaken to assess the value of routine convalescent chest radiography for detection of underlying lung cancer. To investigate the mode of clinical onset of pulmonary carcinoma, 232 inpatients with this diagnosis were also studied. The findings may be summarized as follows: 1) 13/1011 pneumonia patients were found to have previously undiagnosed pulmonary carcinoma; 2) many of these carcinomas (8/13) were disclosed by an acute chest X-ray; 3) pulmonary carcinoma was found by convalescent chest X-ray in 2/88 patients not feeling well and in 2/524 patients feeling well at follow-up, and none of these 4 patients benefitted from the carcinoma diagnosis; 4) ESR was of no value in detecting underlying pulmonary carcinoma at follow-up in patients with pneumonia; 5) of the 232 patients with pulmonary carcinoma, 29 (12.5%) presented with an acute respiratory tract infection; 6) most of these latter patients did not recover as expected and their correct diagnosis was made based on a chest X-ray performed because of persistent symptoms. We suggest that patients with radiologically verified pneumonia undergo clinical examination or are interviewed 4-5 weeks after the onset. If signs or symptoms of respiratory disease persist, chest X-ray should be performed. We consider, however, that routine convalescent chest radiography with the aim of detecting any underlying pulmonary tumour could be omitted if the patient has completely recovered 1 month after the acute onset of illness. PMID- 8460357 TI - Proceedings of the international symposium "Noise and Disease", held in Berlin, September 26-28, 1991. PMID- 8460358 TI - Traffic noise and cardiovascular disease. The Caerphilly and Speedwell studies. PMID- 8460359 TI - Traffic noise as a risk factor for myocardial infarction. AB - The hypothesis that road traffic noise causes ischaemic heart disease (IHD) was tested in several epidemiological studies in middle-aged men. The studies carried out in Caerphilly (Wales) and Bristol-Speedwell (England) suggested the daytime (6-22 h) outdoor traffic noise level category 65-70 dB(A) as a threshold for noise effects detectable. Based on risk factors, a relative risk greater than 1 was calculated for the incidence of major IHD (RR = 1.1) in both samples for the subjects in this highest noise category, those in the quietest (51-56 dB(A)) serving as a reference using multiple models. Also the prevalence of myocardial infarction (RR = 1.2 and 1.1), ECG ischaemia (RR = 1.2 and 1.4) and any IHD disease (RR = 1.2 and 1.2) showed relative risks slightly greater than 1 in this noise group. In contradiction, the observed incidence of major IHD showed relative risks below 1 in both samples in this traffic noise group. The case control studies carried out in Berlin revealed relative risks above 1 on the incidence (RR = 1.3 and 1.2) and the prevalence (RR = 1.2) of myocardial infarction at outdoor traffic noise levels in the range of 71-80 dB(A) serving the men in the category below 61 dB(A) as a reference. None of the findings was statistically significant. The relevance of the results is discussed. PMID- 8460360 TI - The Association for Water, Soil and Air Hygiene. PMID- 8460361 TI - Road traffic noise, noise sensitivity and psychological disorder. AB - The relationship between traffic noise exposure and psychological morbidity was assessed using the population-based Caerphilly Collaborative Survey of 2398 men from Caerphilly, South Wales, UK. The findings showed that annoyance to noise was strongly associated with traffic noise exposure levels. Men with noise sensitivity were more likely to be highly annoyed by noise exposure than men with less noise sensitivity. There was no direct association between noise exposure level and psychological morbidity until the results were stratified by noise sensitivity. This revealed a gradient of increasing psychological morbidity with increasing noise level in the lower two tertiles of noise sensitivity. No gradient was found in the highest tertile of noise sensitivity. The role of noise sensitivity is argued to be either an indicator of vulnerability to environmental stressors or a measure of overreporting. PMID- 8460362 TI - The Institute for Water, Soil and Air Hygiene of the Federal Health Office. PMID- 8460363 TI - A dose-response relationship for occupational noise-induced hypertension. AB - The effect of industrial noise on hypertension prevalence was studied in a group of 1101 female workers in a textile mill in Beijing in 1985. Essentially the entire group had worked in specific workshops in this mill for their full working lives and all had worked for at least five years. The noise levels within the plant were assessed and appear to have been constant since 1954 resulting in a well-defined noise exposure for these workers. A cross-sectional design was used in which blood pressures were determined and questionnaires administered to the workers over a two month period. In addition to demographic information, data was gathered on personal and family history of hypertension, current use of prescription drugs, alcohol, tobacco and salt in the diet. Logistic regression indicated that noise exposure is a significant determinant of hypertension prevalence, but third in order of importance behind family history of hypertension and salt use. Each of the predictor variables exerted an independent influence on risk of hypertension. Cumulative exposure to noise was not an important dose-related variable suggesting that, for those susceptible to the effect, hypertension was manifested within the first five years of exposure. PMID- 8460364 TI - Monitoring hypertension in the work-site. PMID- 8460365 TI - Occupational noise as a cardiovascular risk factor. AB - The results from routine medical screening of 806 workers in a very wide range of different occupational activities were analysed in order to assess the relationship between blood pressure and occupational exposure to noise. Blood pressure was measured for each worker by conventional methods. Noise exposure was estimated according to the main company activity and each worker's specific job, computing three categories of noise exposure: low, medium and high. Preliminary analysis of the data did not reveal any relationship between noise exposure and blood pressure. Nevertheless, when comparing two groups of workers with noise induced hearing loss (NIHL) at 4000 Hz higher and lower than 65 dB, the group with the highest NIHL also shows the highest mean blood pressure value and the highest proportion of hypertensive workers (however, these results are statistically not significant). The limitations and problems posed by the methods used to assess the effects of occupational noise exposure as a cardiovascular risk factor are discussed. PMID- 8460366 TI - Predictors for noise sensitivity: how to use them for a prognostic test. AB - In an exploratory study with the aim of devising a test for noise sensitivity, we had examined the prognostic value of numerous parameters for the development of noise-induced hearing loss. The predictors which showed the highest determination within the framework of a standardized noise exposure were: systolic blood pressure general health finger pulse amplitude recovery temporary threshold shift (TTS) at 12 kHz. The total sample population produced varying patterns of reaction. As we assume that sensitivity occurs when a person with normal hearing reacts in a similar manner to a person with noise-induced hearing loss, we began by extrapolating a standard reaction type for each subsample. We then looked for those parameters where the difference between values with and without exposure was greatest. This step is of considerable significance with regard to the practicability of screening tests. The most sensitive parameters to emerge were: diastolic blood pressure on and off finger pulse reaction TTS between 3 and 6 kHz. We were then able to compare individual reactions with the standard reaction types, taking into account intervention by possible variables. Our results were not uniform, but they permit the conclusion that certain reaction types are genetically determined. This, in turn, suggests that the same might apply to the development of noise-induced hearing loss. PMID- 8460367 TI - Mechanisms of noise-induced inner ear damage. PMID- 8460368 TI - Review: extraaural health effects of aircraft noise. AB - The number of aircraft movements in our society is increasing at a rapid rate. As a consequence the airspace is becoming more crowded, in particular in the vicinity of airports. As a consequence pollution (both air pollution and noise) near the airports increases. One solution to 'rush hours' in the airspace around airports is to spread the number of flights more evenly over time. This leads to more flights in the sensitive parts of the day: evening and night. This leads to community reaction and places the potential health effects of noise in the focus of societal attention. Human functioning is affected by noise in many ways. Effects of noise become detectable at a relatively low noise level, approx. 30 dB(A). Above which noise levels and under what conditions these effects become threatening to health is still largely unknown. This holds true for cardiovascular effects, mental health, mortality rates, medicine consumption, pregnancy, delivery and physical development. On some aspects more certainty exists. Night time noise when it causes people to wake up or prevents them from falling asleep, or when it frequently disturbs the structure of sleep below the waking level, can be detrimental to health. Both for awakening reactions and for annoyance, exposure-response relations are rather well established. Reading ability is hampered by noise. For the vegetative aspects, no clear and stable exposure-response relations are known at this moment. Hopefully this conference will fill in the gap. PMID- 8460369 TI - The federal ministry for the environment, nature conservation and nuclear safety. PMID- 8460370 TI - Specific features of military low-altitude flight noise: criteria for risk of damage and physiological effects. AB - The impact of sound from military low-altitude flying (75 m) is characterized by high maximum levels of up to 125 dB, a rapid rise in sound pressure level (steepest 10-dB slope up to 111 dB/s, mean value 36 dB/s), and occasional (30%) follow-up oscillations of up to around 100 dB. The energy within this broadband sound is very often concentrated primarily in the 0.8 to 4 kHz range. A criterion for the risk of damage can be applied using constant-frequency spectral dose analysis in order to establish, for example, how many overflight events might be regarded as tolerable. We can also draw on findings from animal experiments revealing damage to the extremely sensitive stereocilia of the hair cells in the inner ear to derive a risk assessment which shows that slight impairment to hearing is possible in low-altitude flight zones given either the recorded mean frequency of 17 direct overflights a day (with maximum levels over 100 dB) or else a few extreme isolated events. In laboratory experiments involving exposure to this type of highly dynamic low-altitude flight noise, short-term increases in heart rate (up to 21 beats/min) were found to be much greater than those provoked by other forms of environmental noise with comparable maximum levels (pile driving, gunfire). PMID- 8460371 TI - Psychophysiological and psychiatric tests with children and adolescents in a low altitude flight region. PMID- 8460372 TI - Results of a low-altitude flight noise study in Germany: acute extraaural effects. AB - This paper begins by outlining the aims which our study into the acute effects of low-altitude flight noise set out to achieve. The key question here concerns the relationship between noise parameters (maximum sound level and sound level rise rate) and specific reactions by the individuals affected. The subjects, healthy volunteers, were exposed via earphones to digitally recorded MLAF noise, using sophisticated recording technology. Their reactions were studied on various levels ranging from the subjective experience of negative effects through startle reactions to changes in the cardiovascular and endocrine systems. It emerged that a high sound level rise rate is a physical parameter which leads not only to more physical symptoms being cited by the subjects, but also to more pronounced myokinetic effects of an objectively measurable nature. Studies of circulation physiology were also conducted to throw light on the haemodynamic mechanism of the startle reaction. The findings suggest that increases in cardiac output per minute in a startled subject with a healthy circulation need not necessarily lead to protracted increases in blood pressure. A counter-regulation occurs by means of vasculomotory responses in the muscle. Should this regulatory system be impaired, as may be the case with elderly people, for example, blood pressure increases of up to 45 mm Hg over the initial value may ensure. A sensitization is observed after repeated exposure, with the startle reaction intensifying or else being triggered off by lower sound levels. The sensitization of startle reactions is neuro-physiologically associated with unpleasant or fear-inducing environmental stimuli. Together with the observed increases in plasma hydrocortisone and changes in magnesium metabolism of a type characteristic of stress, this phenomenon of sensitization enables us to establish the hypothetical link between specific acute reactions to MLAF noise and long-term health effects. PMID- 8460374 TI - The Federal Health Office. PMID- 8460373 TI - Results of a low-altitude flight noise study in Germany: long-term extraaural effects. PMID- 8460375 TI - Results of a low-altitude flight noise study in Germany: aural effects. PMID- 8460376 TI - The influence of military low-altitude flight noise on the inner ear of the guinea pig. Part I: Hearing threshold measurements. AB - The auditory thresholds of about 60 anaesthetized guinea pigs were determined at 3 or 4 frequencies between 2 and 20 kHz using the acoustically evoked brain stem potentials. The animals were then exposed to electro-acoustically reproduced MLAF noise with peak levels between 120 and 130 dB(A). The exposure occurred either once or else four times within either 3 or 60 minutes. The level of noise increased at 7.5 and 75 dB/s (slow and fast increase). TTS was then determined. PTS was measured one week later. In over half the animals, exposure to rapidly increasing noise level with a peak of 126 dB(A) induced PTS > or = 30 dB for at least one frequency. Exposure to a slowly increasing noise level with the same peak provoked significantly smaller PTS. 4 exposures to a rapidly rising noise level within 3 minutes induced significantly smaller PTS than the same dosage within 60 minutes. Only in the latter case was PTS greater than TTS. PMID- 8460377 TI - The influence of military low-altitude flight noise on the inner ear of the guinea pig. Part II: Scanning electron micrographs. AB - Guinea pigs were exposed once to MLAF noise (126 dB(A), 75 dB/s) and 12 cochleae were prepared for scanning electron microscopy 2 to 3 weeks after exposure. Qualitative analysis of the cilia of the outer hair cells revealed the types of damage already described in literature. The spatial distribution of cilia damage, however, differed essentially from the well known pattern: the damage was more or less pancochlear, beginning in the basal turn and increasing in frequency and severeness of damage till the end of the third turn. The most severe damage was visible in the outer row of the outer hair cells. This special pattern of cilia damage indicates that MLAF noise causes a different type of damage than the types described in literature. More studies are needed. PMID- 8460378 TI - Feasibility of a study on the effects of military aircraft noise. PMID- 8460379 TI - The influence of nocturnal aircraft noise on sleep and on catecholamine secretion. AB - The influence of noise from night flying on electro-biological reactions and on the secretion of catecholamines (adrenaline and noradrenaline) was studied in eight healthy adults whose place of residence exposes them to day-time aircraft noise. The interrelationships were then analysed, with daytime noise exposure, personality traits and general day-to-day condition reflected in control variables. The subjects were each observed during five nights without noise exposure (Leq < 32 dB(A)) and five nights with noise exposure (Leq = 36 to 56 dB(A)), when the following factors were varied: number of flights (16, 32, 64 overflights with a constant maximum indoor sound level of 75 dB(A)); and sound level (64 overflights at a maximum indoor sound level of 55, 65 and 75 dB(A)). All these flights were transmitted electro-acoustically between the third and sixth hours of the night. When the various daytime exposures are taken into account, significant mean value differences between noisy and peaceful nights are demonstrated in 8-hour urine for both catecholamines. In the case of adrenaline, the original data already showed a significant increase with noise exposure. Furthermore, catecholamine concentration increases with sound level. The analysis confirms a close link between the volume of adrenaline in the urine collected and electro-biological reactions, with consideration given to personality traits and day-time alcohol consumption. PMID- 8460380 TI - The Federal Environmental Agency. PMID- 8460381 TI - Night aircraft noise index and sleep research results. AB - A number of countries have introduced regulations for the protection of people living around airports against the high level of aircraft noise. Certain noise indices have been determined for 24-hour periods, others for extended daytime periods, while a few are weighted for the noise occurring during the night. The noise environment problem limits the development of airports and any reduction of the noise at source is balanced by the increase in air traffic so that the overall noise level around airports remains high. The only possibility for the expansion of traffic is during the night and the airport authorities are interested in this solution for airports that remain open at night and in the case of proposals for some new airports in Western Europe. Research yields some useful results with regard to our understanding of the effects of noise and the duration and quality of sleep of people living around airports. In this paper we consider how these results can be used in proposing some noise criteria corresponding to the preservation of a certain quality of sleep. PMID- 8460382 TI - A comparison between the impact of noise from aircraft, road traffic and trains on long-term recall and recognition of a text in children aged 12-14 years. AB - A total of 417 students in the seventh grade, 12-14 old, took part in three 15 min learning sessions in their ordinary class-rooms. Their task was to read a text, and they were tested one week later with difficult recall questions and less difficult recognition items on the text. The first session was a pretest for their learning abilities. This session was run in ambient noise conditions and all the students read the very same text. The scores from this session were employed to split the pupils along the median into two groups of learning ability. Sessions two and three were counterbalanced as a noise condition or an ambient noise condition. In these sessions two other texts were employed, and they appeared equally often under the noise and ambient conditions, as well as under the two different presentation orders. Three subgroups of the pupils were exposed to aircraft noise, train noise and road-traffic noise. The noise types were of the same equivalent level (66 dB(A) Leq) in all subgroups. The design of the study permitted two different analyses of long-term learning. First, in a within subject analysis, the difference scores between the noise and ambient noise conditions in session 2 and 3 were calculated, and crossed with learning ability (high and low) and type of noise. In a second between subject analysis, the difference scores in session 1 and 2 were crossed with the group factor whether they had noise or ambient conditions in session 2, and the ability and noise type factors. Both analyses yielded the same results. Noise impaired long term recall of the difficult items. Degree of impairment on the recall items did not interact with noise source or learning ability. The average impairment due to aircraft and road traffic noise was around 23% of the scores. Train noise had no effect. For the easy recognition items there were no effects of noise exposure, nor of its interaction with noise source and learning ability. Since the number of pages read did not differ between noise and ambient conditions, an explanation in terms of distraction is ruled out. The results are discussed in terms of arousal and cognitive overload. PMID- 8460383 TI - Increase in mortality rates due to aircraft noise. AB - In a study using data from the 1970-1980 decade, we find that people near Los Angeles International Airport (LAX) suffer a 5% increase in mortality rates due to increases in a number of fatal diseases. We comment also on the effect of changes in noise level over the last decade. It is found that there is an 18% increase in cardiovascular deaths, for people over 75 at a 97% confidence level, in areas around the airport. Approximately 200,000 people are involved in the study, split into two groups, test and control, near LAX. The two areas were adjusted to be alike in race, age and economic level. The number of suicides in the age bracket 45-54 was increased by the jet noise by over 100% at a 99% confidence level. Total accidental deaths increased by over 60% in the age group above 75 at a 96% confidence level. If we add together all increases there are an average of 24 extra deaths due to aircraft, primarily jet, noise in the high noise area. If we included all people living within the extended high noise contour, there is reason to believe that there is an increase of over 60 deaths in the LAX area per year. PMID- 8460384 TI - Selected aspects of cardiovascular responses to acute stress. PMID- 8460386 TI - Cardiovascular risk factors and magnesium: relationships to atherosclerosis, ischemic heart disease and hypertension. PMID- 8460385 TI - Legal aspects of noise abatement for the protection of health. PMID- 8460387 TI - Can dietary magnesium supplementation decrease coronary heart disease and sudden cardiac death? PMID- 8460388 TI - Extraaural effects of chronic noise exposure in animals--a review. PMID- 8460389 TI - Influence of magnesium on drug- and noise-induced inner ear damage. Animal studies. PMID- 8460390 TI - Oral magnesium supplementation as prophylaxis for noise-induced hearing loss: results of a double blind field study. AB - The effect of oral Mg-supplementation as prophylaxis against noise-induced hearing loss was tested in a placebo-controlled double blind study involving 320 voluntary subjects during a 2-month period of military training. The hearing thresholds of all subjects were checked and only persons with normal hearing were accepted. Before and after the 2-month training, blood samples were collected and Mg was analysed in serum, erythrocytes and lymphocytes. Seven days after the last exposure to firearm noise, the audiograms of all test subjects were checked and permanent threshold shifts (PTS) were determined. The total group received a drink containing either 4g Mg granulate verum (6.7 mmol Mg aspartate) or placebo every working day during the 2-month training period. The primary source of noise exposure were firearms: 420 shots per person, mean peak level 164 dB(A). The recruits used ear plugs with a mean insertion loss of 25 dB. In both groups Mg concentration in serum and in erythrocytes increased with time. Lymphocyte Mg increased in the Mg group only. In the placebo group the percentages of ears with PTS > 25 dB at 4 kHz/6 kHz and/or 8 kHz after exposure to firearm noise were twice as high as in the Mg group. PMID- 8460391 TI - Do magnesium infusions protect the inner ear during middle ear surgery? A randomized double blind study. AB - Joachims et al. recently demonstrated that magnesium was able to protect the inner ear during exposure to noise and fire arms. During middle ear surgery, the inner ear is subjected to noise from fraising and drilling. We saw fit, therefore, to conduct a random double blind study to establish whether magnesium infusions would protect the inner ear during middle ear surgery. We examined 80 patients (38 verum, 42 placebo). The verum patients received 10 mg/kg body weight magnesium 12 hours and 1 hour prior to operation. Plasma and red cell magnesium levels were measured pre-operatively and intra-operatively; they rose as expected. Post-operative auditory tests showed that magnesium had no tendency to prevent inner ear damage. Advocates of magnesium criticize the limited number of patients in our study as well as the administration of the magnesium substitute. In our opinion, however, it should be borne in mind when evaluating these findings that noise from drilling and fraising is only one factor among many which can induce inner ear injury during middle ear surgery. PMID- 8460392 TI - Extraaural effects of chronic noise exposure on blood pressure, microcirculation and electrolytes in rats: modulation by Mg2+. AB - Rats maintained on normal Mg-containing diets for 12 weeks (plasma Mg = 0.96 +/- 0.02 mmole) and subjected to 85 dB(A), 12 h per day for 8 weeks; 95 dB(A), 16 h per day for 4 weeks demonstrated significant elevation in systolic and diastolic arterial blood pressure (ABP); plasma Mg showed a 15% decrease whereas aortic and portal vein muscle exhibited slight reductions in Mg content and elevation in Ca. Moderate (plasma Mg = 0.67 +/- 0.03 mmole) and more severely (plasma Mg = 0.28 +/ 0.01 mmole) Mg deficient animals not subjected to audiogenic stress (AS) also exhibited significant elevations in systolic and diastolic ABP; vascular tissue Mg content decreased whereas Ca content rose. Animals subjected to combined Mg deficiency and AS for 12 weeks exhibited the greatest deficits in plasma and vascular muscle Mg and the greatest elevations in systolic and diastolic ABP; vascular tissue Ca contents also showed the greatest increases. In-situ measurements of mesenteric arterioles, venules and precapillary sphincters in the various subgroups revealed negative correlation between the lumen sizes of these microvessels and plasma Mg. Also, there was an inverse correlation between plasma Mg and ABP. Capillary blood flow transit times were decreased in relation to the degree of plasma Mg reduction. A quantitative rarefication of true capillaries per mesentery was observed. In addition, vascular reactivity of terminal arterioles to constrictor agents (norepinephrine, angiotensin II, Ba2+) was in relation to the plasma and vascular tissue deficit in [Mg]. Reactivity to the dilator agent, histamine, decreased in proportion to Mg deficit. A rationale for therapeutic intervention with Mg may evolve from these studies. PMID- 8460393 TI - Review: extraaural health effects of chronic noise exposure in humans. AB - Thirty-one epidemiologic studies published in the English literature since 1980 were reviewed to integrate the findings on effects of chronic industrial and traffic noise exposure on circulatory and cardiovascular diseases. Methodologic issues relevant to quantifying noise-induced risk are discussed. Although there has been some improvement over the decade, the quality of the research remains low. Cross-sectional studies continue to dominate. Studies to date show contradictory results, neither confirming nor invalidating the hypothesis that persons with prolonged exposure to high noise levels have an increased risk of high blood pressure and cardiovascular disease. Prevalence ratios for hypertension between high and low noise groups range from 0 to 3.1. The more methodologically rigorous studies report the lower associations. Differences in mean blood pressures detected have been relatively small, ranging from 0-10 mm Hg. No consistent pattern of findings on cardiovascular effects other than blood pressure has been reported. It is concluded that the quality of the research remains inadequate or inadequately reported for quantifying noise-induced risk. Prospective studies whose design accounts for potential confounding variables and effect modifiers are required before useful inferences may be drawn. PMID- 8460394 TI - Mutational analysis in a patient with a variant form of Gaucher disease caused by SAP-2 deficiency. AB - It is now clear that the lysosomal hydrolysis of sphingolipids requires both lysosomal enzymes and so-called sphingolipid activator proteins (SAPs). One gene, called prosaposin, codes for a precursor protein that is proteolytically cut into four putative SAPs. These four SAPs, of about 80 amino acids, share some structural features but differ somewhat in their specificity. Domain 3 of prosaposin mRNA contains the coding region for SAP-2, an activator of glucocerebrosidase. While most patients with Gaucher disease store glucosylceramide due to defects in glucocerebrosidase, a few patients store this lipid in the presence of normal enzyme levels. In this paper we describe the identification of a point mutation in domain 3 of a patient who died with this variant form of Gaucher disease. Polymerase chain reaction amplification was performed in the small amount of genomic DNA available using primers generated from the intronic sequence surrounding domain 3. The patient was found to have a T-to-G substitution at position 1144 (counting from the A of ATG initiation codon) in half of the M13 recombinant clones. This changes the codon for cysteine382 to glycine. His father and unaffected brother also had this mutation, but his mother did not. She was found to have half of the normal amount of mRNA for prosaposin in her cultured skin fibroblasts. Therefore, this child inherited a point mutation in domain 3 from his father and a deficiency of all four SAPs coded for by prosaposin from his mother. PMID- 8460395 TI - Chromosomal localization of a sequence with in vivo activity for initiation of DNA replication. AB - The genomic fragment containing the sequence of human cDNA clone 343, previously characterized as capable of autonomous replication upon transfection into mammalians cells and occupying a genomic region inclusive of an initiation zone for DNA replication, was mapped on human chromosome 6q22-qter by a combination of in situ hybridization and G-banding. Southern blot hybridization with a panel of human-hamster somatic cells confirmed the location of the 343 gene on chromosome 6. Fragile sites have been mapped to the region at 6q21 and 6q26. Several neoplastic disorders, including melanoma, acute nonlymphocytic leukemia, acute lymphocytic leukemia, and malignant lymphoma, have also exhibited translocations and deletions involving the region 6q21-6q27. PMID- 8460396 TI - Chromosomal location and structure of amplicons in two human cell lines with coamplification of c-myc and Ki-ras oncogenes. AB - Gene amplification is a major mechanism through which oncogenes and genes responsible for drug resistance are overexpressed in neoplastic cells, and several models for structure of amplified units (amplicons) are postulated. In order to identify consistent changes associated with oncogene amplification, we analyzed chromosomal location and physical distance of amplicons of two independent human cell lines that have coamplified c-myc and Ki-ras oncogenes. In one cell line, KHC287, amplified c-myc genes were localized in two chromosomes and Ki-ras in three chromosomes. One marker chromosome was almost entirely encompassed by both amplified genes. In the other cell line, Lu-65, both of the amplified genes shared the same locus, on chromosome 12q+. The two genes, however, are more than 1500 kb apart in both cell lines. The above findings indicate that two different amplified genes became associated on one chromosome in two independent cell lines. This suggests that a common mechanism is associated with chromosomal rearrangements affecting different amplified genes. PMID- 8460397 TI - A hamster-human subchromosomal hybrid cell panel for chromosome 2. AB - We have constructed hamster-human hybrid cell lines containing fragments of human chromosome 2 as their only source of human DNA. Microcell-mediated chromosome transfer was used to transfer human chromosome 2 from a monochromosomal mouse human hybrid line to a radiation-sensitive hamster mutant (XR-V15B) defective in double-strand break rejoining. The human chromosome 2 carried the Ecogpt gene and hybrids were selected using this marker. The transferred human chromosome was frequently broken, and the resulting microcell hybrids contained different sized segments of the q arm of chromosome 2. Two microcell hybrids were irradiated and fused to XR-V15B to generate additional hybrids bearing reduced amounts of human DNA. All hybrids were analyzed by PCR using primers specific for 27 human genes located on chromosome 2. From these data we have localized the integrated gpt gene on the human chromosome 2 to the region q36-37 and present a gene order for chromosome 2 markers. PMID- 8460398 TI - Multiple DNA-protein interactions at the CpG island of the human pseudoautosomal gene MIC2. AB - The human MIC2 gene is pseudoautosomal and in females it escapes X inactivation. At the 5' end of the gene a 1.2-kb-long CpG island has been identified that is unmethylated on the active X, the inactive X, and on the Y chromosome. We have demonstrated by 5' RACE experiments that this region contains the transcription start site of the gene. To better characterize this CpG island, we have investigated the interaction between this region and nuclear proteins in vitro by using DNA gel mobility shift and DNase I footprinting techniques. Band shift experiments with HeLa cell nuclear extract have indicated that all the island is involved in multiple interactions with nuclear proteins. Experiments with a eukaryotic purified Sp1 protein have shown that this factor specifically binds to several sites of the island. Three DNase I protected footprints have been identified in the region between nucleotides -122 and +34 with respect to the transcription initiation site. By using a recombinant Sp1 protein, we have shown that all the footprints are due to the binding of Sp1. The sequences of two footprints correspond to the decanucleotide binding site for Sp1, the sequence of the third one does not contain any published Sp1 recognition site. PMID- 8460399 TI - An evaluation of the inactive mouse X chromosome in somatic cell hybrids. AB - The expression of mouse Zfx, Rps4, Ube1x, and Xist was evaluated in hamster-mouse somatic cell hybrids containing either an active or an inactive mouse X chromosome using polymerase chain reaction of reverse transcribed RNA (RT-PCR). The results showed that Zfx, Rps4, and Ube1x are expressed exclusively from the active mouse X, while Xist is expressed exclusively from the inactive X. These findings confirm the pattern of X inactivation for these mouse genes reported previously based on expression in somatic tissues of F1 females from interspecific crosses. These results demonstrate the existence of differences between human and mouse X inactivation, as the corresponding human genes, ZFX, RPS4X, and UBE1 escape X inactivation. PMID- 8460401 TI - Complementation of DNA repair defect in xeroderma pigmentosum cells of group C by the transfer of human chromosome 5. AB - Complementation of DNA excision repair defect in xeroderma pigmentosum cells of group C (XP-C) has been achieved by the transfer of human chromosome 5. Individual human chromosomes tagged with a selectable marker were transferred to XP-C cells by microcell fusion from mouse-human hybrid cell lines each bearing a single different human chromosome. Analysis of the chromosome transfer clones revealed that introduction of chromosome 5 into XP-C cells corrected the DNA repair defect as well as UV-sensitive phenotypes, while chromosomes 2, 6, 7, 9, 13, 15, 17, and 21 failed to complement. The introduced chromosome 5 in complemented UVr clones was distinguished from the parental XP-C chromosomes by polymorphism for dinucleotide (CA)n repeats at two loci, D5S117 and D5S209. In addition, an intact marked chromosome 5 was rescued into mouse cells from a complemented UVr clone by microcell fusion. Five subclones of a complemented clone that had lost the marked chromosome 5 exhibited UV-sensitive and repair deficient phenotypes identical to parental XP-C cells. Concordant loss of the transferred chromosome and reappearance of XP-C phenotype further confirmed the presence of a DNA repair gene on human chromosome 5. PMID- 8460400 TI - Mapping of the genes for human endoplasmic reticular heat shock protein gp96/grp94. AB - The murine tumor rejection antigen gp96 (TRA1, mapped to mouse chromosome 10) is a member of the heat shock protein family. Using a fragment of the murine gp96 cDNA as a probe, three gp96-related human genes have been isolated and structurally characterized. They have been mapped to human chromosomes 1 (p22), 12 (q24.2-->q24.3), and 15 (q25-->q26) by Southern blot hybridization and in situ hybridization of gene-specific probes. Only one of the genes, designated TRA1 (human chromosome 12) is a coding gene; the other genes (TRA1P1 and TRAP2) appear to be independently derived, processed pseudogenes. PMID- 8460402 TI - Analysis of large deletions in the HPRT gene of primary human fibroblasts using the polymerase chain reaction. AB - Spontaneous and X-ray-induced mutants of the HPRT gene were isolated from two primary human fibroblast lines. The limited life-span of the mutants restricted the use of methods requiring large quantities of DNA, and the polymerase chain reaction (PCR) was used in particular to check for the presence of multiple genomic sites in mutant analysis. Robust PCR primers were designed to amplify sites of up to 1 kb, mostly with 1-kb spacings between sites, over the entire 56 kb HPRT gene region. Using PCR, large deletions were found in 43% of independent X-ray-induced mutants, and their breakpoints were localized where these fell within the gene. Anonymous DNA sites in the Xq26 chromosomal region containing HPRT (covering > or = 1.5 Mb) were also amplified by PCR to assess codeletion with HPRT; sites up to 1 Mb distal to the gene (DXS86, DXS10) were codeleted in some mutants, but no mutant was found with loss of a proximal site (DXS79). PMID- 8460403 TI - Accuracy of computed tomography in predicting adrenal tumor size. AB - We undertook a multi-institutional, retrospective study of 51 patients with adrenal tumors (pheochromocytomas, functioning and nonfunctioning cortical adenomas, cysts and carcinomas). All patients had computed tomography (CT) with a maximum of 5 millimeter cuts the week before undergoing complete adrenalectomy. Pathologists were asked to measure the tumor to the nearest 0.1 centimeter. Tumor size obtained from pathologic reports (actual size) and CT reports (estimated size) were compared. Adrenal tumors were divided into two groups on the basis of size--tumors with actual size of 6 centimeters or greater and tumors with actual size of less than 6 centimeters. Statistical analysis was performed with Newman Keuls analysis of variance. After controlling for tumor type and for the institution at which the measurement was made, we found that CT consistently underestimated adrenal tumor size in both tumor groups. Moreover, the average, underestimated difference for tumors 6 centimeters or greater was 32 percent, but 47 percent for tumors less than 6 centimeters (p = 0.060). CT seemed to underestimate the size of small adrenal tumors more than large tumors. Because the decision to operate on solid, nonfunctioning adrenal tumors is based on tumor size and because CT is currently the standard technique used to estimate size, our findings need to be considered before undertaking surgical treatment. PMID- 8460404 TI - The role of CA 125 and conventional examinations in diagnosing progressive carcinoma of the ovary. AB - The clinical significance of the serum marker CA 125 and conventional examinations in diagnosing progressive disease was evaluated in 98 patients. The examinations included CA 125, gynecologic and complete physical examination, abdominal computed tomography (CT), roentgenogram of the chest, second look operation and serum biochemistry profile. Progressive disease occurred in 49 patients and the time to progression was a median of 12 months (range of four to 52 months). At the time of progression, an elevated CA 125 was found in 73 percent of the patients, and in 63 percent of the patients, CA 125 increase preceded clinical progression for a median of four and one-half months (range of 0.5 to 29.5 months). A positive gynecologic examination at progression was found in 67 percent of the patients, physical examination and abdominal CT scan were positive in 30 percent, intervention operation in 14 percent and roentgenogram of the chest in 12 percent of the patients. With the combination of serum CA 125, gynecologic and general physical examination, progressive disease could be diagnosed in 92 percent of the patients. The false-positive rate in the 49 patients with no evidence of disease was 1.6 percent for CA 125, 2.0 percent for gynecologic examination, 4.0 percent for physical examination, 14.0 percent for CT scan and 2.0 percent for roentgenograms of the chest. Serum CA 125 is the most reliable examination to detect progressive disease early. With the combined use of serum CA 125 and the gynecologic and general physical examination, progression of the disease can be detected in about 90 percent of the patients. PMID- 8460405 TI - Analysis and prevention of recurrent goiter. AB - The current study was done to analyze our experience with recurrent goiter. Prevention must be stressed because reoperations of the thyroid gland present technical difficulties and are associated with an increased risk of hypoparathyroidism and permanent hoarseness. Nodular recurrences occurred in 36 of 1,456 patients (2.5 percent) who underwent thyroidectomy between 1968 and 1983. All patients had the initial operation at Jean Bernard Hospital, Poitiers, France, and had follow-up evaluation from five to 20 years. Multinodular goiter accounted for 70 percent of the recurrences. Sixty percent of the recurrences were in patients with multinodular goiters. Recurrent goiter was usually first detected about eight years after thyroidectomy. Thirty patients with recurrence had reoperations. Two patients had paralysis of the vocal cord and one patient had permanent hypoparathyroidism. Recurrent goiter may occur because of the development of new nodules (true recurrence) or because of the growth of "residual" or persistent macroscopic or microscopic nodules left at the previous thyroid operation. Intraoperative digital palpation of the entire thyroid gland is essential for detecting residual macroscopic thyroid nodules, and all enlarged nodules should be removed. Thyroid-stimulating hormone (TSH) suppressive therapy is recommended by some authorities to prevent "true" recurrences, although its efficacy is debated. Since recurrence is uncommon in the current series, perhaps TSH suppressive therapy should only be used in high-risk patients. In the current experience, only the multinodular character of the nodules in euthyroid patients has a significant correlation with subsequent development of recurrent goiter (p < 0.01), and one must consider patients with multinodular goiter at risk for recurrence. Once TSH treatment is begun, it will logically be continued for life. Total thyroidectomy has been recommended by some endocrine surgeons for treating patients with multinodular goiter. We prefer subtotal thyroidectomy and reserve total thyroidectomy for patients when no normal thyroid tissue can be preserved because only 2.5 percent of the patients in the current study had recurrent goiter. Prevention of residual nodules is probably best assured by systematic palpation during operation of the two thyroid lobes. This considerably lessens the risk of recurrence. Since nodular recurrences occurred in only 2.5 percent of the patients in the current study, although multinodular goiter must be considered at risk for recurrence, we do not recommend systematic total thyroidectomy in multinodular goiter. PMID- 8460406 TI - Clinical experience with an inlay expanded polytetrafluoroethylene soft tissue patch as an adjunct in inguinal hernia repair. AB - Fifteen percent of 2,331 inguinal hernias required a biomaterial to effect a tension-free repair. Using the anterior approach, a graft placed deep to the posterior wall fulfills all the requirements of a sound operation. The procedure is normally performed using local anesthesia in an ambulatory facility. Three hundred fifty inguinal hernias were repaired using an expanded polytetrafluoroethylene soft tissue inlay patch. Ninety-one percent of the patients had personal follow-up examination with a mean follow-up period of 41.8 months. There were four recurrences. PMID- 8460407 TI - Ritual head computed tomography may unnecessarily delay lifesaving trauma care. AB - Examination of 462 consecutive patients with blunt trauma suggested reassessment of the timing of head computed tomographic (CT) scanning in the critical care of the seriously injured. Even though potential brain injury was the most common reason for admission, few (5 percent) of the patients required neurosurgical intervention. It is apparent that the more common non-neurosurgical procedures that were used to squelch hemorrhage and provide hemodynamic stability and airway control should not be delayed to obtain "routine" head CT scans. PMID- 8460408 TI - Diagnoses after laparotomy for a mass in the pelvic area in women. AB - The management and outcome of 80 women with an undiagnosed pelvic mass who were referred to the Gynecologic Oncology Division at the University of Rochester during a one year period were reviewed. All patients underwent an exploratory laparotomy for definitive diagnosis. We correlated the final diagnosis with the results of preoperative evaluation and intraoperative assessment. Of the 80 patients, 48 were diagnosed with malignant disease. Of patients with carcinoma, 32 had carcinoma of the ovaries, two had other gynecologic malignancies, ten had nongynecologic malignancies and four had synchronous gynecologic and nongynecologic carcinomas. Carcinoma of the colon and rectum was the most common nongynecologic carcinoma; other malignant diseases were found in the endometrium, vagina, colon and rectum and the breast as well as lymphoma. Preoperative roentgenographic examinations and colonoscopy only had a sensitivity of 38 percent in detecting primary carcinoma of the colon and rectum. Ultrasound of the pelvic region and computed tomographic scan of the abdomen did not improve prediction of malignant disease in the patient population. Serum CA 125 was elevated in 26 of 37 patients with a carcinoma; however, it was elevated with relatively equal frequency in carcinomas of the ovaries and colon and rectum. Intraoperative frozen section accurately identified the primary site of the disease in 90 percent of the patients. However, in the presence of a tumor in the ovaries, carcinomatosis and a tumor in the colon, the results of frozen section were erroneous in four of six patients. Because preoperative assessment seems to be of limited value in excluding nongynecologic lesions, we recommend that pelvic surgeons be prepared to manage operatively a variety of malignant disease or have appropriate consultation available at laparotomy. PMID- 8460409 TI - Heparin improves oxygenation and minimizes barotrauma after severe smoke inhalation in an ovine model. AB - Inhalation injury is one of the main causes of mortality in burn victims. The tracheobronchial epithelium sloughs and combines with a protein rich exudate to form casts of the airways that can lead to obstruction. We studied the effects of a continuous infusion of heparin on the acute pulmonary injury that occurs after smoke inhalation injury in sheep. Twelve ewes with vascular catheters received a standardized smoke inhalation injury and mechanical ventilation according to protocol for 72 hours. The heparin group (n = 6) received a 400 unit per kilogram bolus of heparin followed by a continuous infusion to maintain the activated clotting time between 250 to 300 seconds. The control group (n = 6) received a saline solution vehicle. Hemodynamics, blood gases and plasma samples for conjugated dienes were taken every six hours. At necropsy, pulmonary tissue was collected for histologic findings, polymorphonuclear neutrophil leukosequestration, wet-to-dry weight ratios and conjugated dienes. PaO2 to FIO2 ratios were improved in the heparin group compared with the control group at 12 to 72 hours after injury, and peak airway pressures were higher in the control group compared with the heparin group. Positive end expiratory pressure requirements were higher in the control group compared with the heparin group. There were significantly fewer airway tracheobronchial casts as determined by our tracheobronchial casts scoring system (2.4 +/- 0.4 versus 0.67 +/- 0.21) and confirmed by histologic examination. Pulmonary blood-free wet-to-dry weight ratios were higher in the control group compared with the heparin group (6.4 +/- 0.5 versus 5.2 +/- 0.1; p < 0.05). There were no differences in pulmonary tissue or plasma conjugated dienes; likewise, pulmonary leukosequestration was unaffected by heparin. Heparin decreases tracheobronchial cast formation, improves oxygenation, minimizes barotrauma and reduces pulmonary edema in an ovine model of severe smoke inhalation injury. Heparin does not reduce oxygen free radical activity after smoke inhalation injury. PMID- 8460411 TI - Immediate flap coverage in the treatment of large surgical defects after tumor resection. AB - Fifty-one patients with large surgical defects after tumor resection (range of 100 to 1,050 centimeters squared, mean of 259 centimeters squared) were treated with immediate flap coverage. Indications for flaps were exposed vital structures, a wound bed unsuitable for skin grafting or planned postoperative radiation. Patients were divided into three groups based on tumor location--head and neck, trunk and perineum and groin and extremity. Sixty-eight flaps (11 free and 57 pedicled) were used and all wounds ultimately healed. Overall, extensive complications occurred in eight patients, lesser complications in 11 patients and initial flap loss in three patients. While complications delayed healing, all defects were ultimately successfully covered using flaps. Preferred flap choices for each anatomic area are presented. By providing immediate coverage of these massive defects, flaps allow wide tumor resection that improves palliation and chance for cure. Flaps tolerate postoperative radiation well and do not obscure recurrence if careful follow-up examination is given. PMID- 8460410 TI - The management of vascular injuries of the extremity associated with civilian firearms. AB - A penetrating extremity trauma registry was created to prospectively study the physical findings, use of arteriography, nonoperative management with embolization or observation and operation in the management of vascular injuries. During a recent ten month period, 228 patients with 320 injuries of the extremity secondary to firearms were admitted to the Trauma Service. Twenty-four percent of the patients had more than one injury, and there were six perioperative deaths related to associated injuries. Fifty-one patients had 50 arterial and 17 venous injuries. Limb salvage was 100 percent. Twenty-two patients with obvious arterial injuries were taken directly to the operating room without arteriography. Arteriography was performed immediately after admission in 41 patients and the findings were positive in 46.4 percent of the patients; nine required operation. Arteriography was performed for injuries in proximity to a major vessel as the indication in 153 injuries and revealed seven arterial injuries (4.6 percent). Three patients underwent operation. Five patients with arterial injuries had successful embolization during the initial arteriography and five patients with intimal injuries were observed, four healed and one patient was lost to follow-up evaluation. Operative repair of arterial injuries included the use of saphenous vein (21 patients), prosthetic grafts (seven patients) and ligations (four patients). Seventeen venous injuries were either repaired (eight patients) or ligated (nine patients). In the patients undergoing operative repairs, 68.7 percent had fasciotomies performed. The excellent results in the current study (no amputations with 51 survivors of arterial injuries) were obtained by a multidisciplinary approach, involving selective arteriography to avoid unnecessary operation and operative repair in those with extensive vascular injuries. The use of arteriography for proximity characterized a few vascular injuries requiring operation or observation. It should serve as the standard for evaluating noninvasive diagnostic studies and for studying the natural history of asymptomatic injuries. PMID- 8460412 TI - Clinical correlates of false-negative fine needle aspirations of the breast in a consecutive series of 1,005 patients. AB - Fine needle aspiration (FNA) of the breast is a useful diagnostic tool in the management of lesions of the breast. However, false-negatives invariably occur and can detract from the usefulness of the technique. The current study of 16 patients with false-negative FNA of the breast from a consecutive series of 1,005 patients was undertaken in an attempt to better understand the clinical correlates most often associated with false-negative diagnoses. Pre-FNA physical examination and mammographic findings were correlated with the gross and microscopic features of these 16 patients. All 16 patients had palpable findings. Mammographic abnormalities were divided into three categories--highly suspicious for malignant tumor (n = 7), indeterminate (n = 3) and negative (n = 4). Mammograms were not available for two patients. The carcinomas ranged in size from 0.8 to 6.5 centimeters (mean of 1.9 centimeter). Thirteen of 16 carcinomas were 2 centimeters or less. Of the small tumors, histologic factors revealed no special type (NST) in six patients and special type carcinoma in seven patients. The notably large tumor (6.5 centimeters) was of high grade and demonstrated an unusual diffusely infiltrative pattern histologically extending between normal mammary lobules. Overall, special type carcinomas comprised seven of 16 patients. All of these carcinomas, as well as six of nine NST were paucicellular, that is, more than 20 percent area containing tumor cells. The current study supports the findings of others that small tumor size, paucicellularity and special type histologic factors contribute to false-negative diagnoses of FNA of the breast. PMID- 8460413 TI - Obstetrics and the general surgeon. AB - From a small Pacific island country of Tuvalu, an analysis of 132 obstetric and gynecologic patients operated upon by one general surgeon during a 20.5 month period from 1988 to 1989 was performed. The operations comprised 50 percent of all surgical procedures and were associated with complicated pregnancy and delivery in 48 percent of the patients, birth control and infertility in 34 percent and gynecologic neoplasms, infections and bleeding ex utero in 18 percent. There was no mortality and 11 patients had lesser complications. Of the 38 cesarean sections, 76 percent were emergency operations. The main indications for cesarean section were dystocia in 55 percent of the patients and previous cesarean section in 24 percent. There was no maternal mortality. The complication rate was 13 percent and included two neonatal deaths. The cesarean birth rate during the study period was 7.6 percent, a nearly fivefold increase from the previous 9.5 years. With other factors remaining unchanged, the increase in cesarean birth rate corresponded to a decrease in neonatal death rate from 35.7 to 15.7 per 1,000 live-born infants. It is concluded that a considerable share of work of a general surgeon in developing countries consists of obstetric and gynecologic procedures. This should be taken into consideration when training and recruiting surgeons for that kind of work. A general surgeon with obstetric experience can perform cesarean section with an acceptable morbidity rate and should not hesitate to do it whenever labor does not progress as expected. The decision to operate can be based on physical examination with close cooperation with the midwife. In developing countries, increasing cesarean birth rates alone seem to reduce considerably the neonatal death rates. PMID- 8460414 TI - T-cryptantigen determination affects mortality in necrotizing enterocolitis. AB - Testing of infants suspected of having necrotizing enterocolitis for evidence of exposure of the Thomsen-Friedenreich cryptantigen (TCA) has been advocated, because patients with TCA exposure can have severe hemolytic reactions when undergoing transfusion with plasma containing blood products. We compared 62 patients who were managed with knowledge of TCA exposure status during a four year period with 66 patients who were not screened during a comparable four year period. Evidence of hemolysis after blood transfusion occurred significantly more frequently in patients who were not screened (42 versus 15 percent, p < 0.05) and there was significantly greater mortality (18.0 versus 4.5 percent, p < 0.05) in the group that was not screened. These findings suggest that screening for TCA exposure is not only of diagnostic and prognostic value in necrotizing enterocolitis, but is important for patient management and outcome. PMID- 8460415 TI - Protective effects of therapy with a protease and xanthine oxidase inhibitor in short form pancreatic biliary obstruction and ischemia in rats. AB - The current study was done to evaluate the effects of short term (60 minutes) pancreatic biliary duct obstruction (PBDO) with intraductal hypertension (IDH) stimulated by secretin (0.2 clinical unit per kilogram per hour) and caerulein (0.2 microgram per kilogram per hour) plus 30 minutes of temporary pancreatic ischemia (ISCH) produced by ligation of celiac and superior mesenteric artery on the exocrine pancreas and protective effects of a new potent protease inhibitor, ONO3307 in combination with xanthine oxidase inhibitor, allopurinol, in this multifactor related model of acute pancreatitis in rats. Twelve hours after PBDO with IDH plus ISCH, we observed hyperamylasemia (23 +/- 3 units per milliliter) (p < 0.01); moderate pancreatic histologic changes; pancreatic edema (water content--81 +/- 2 percent) (p < 0.02), as well as the impaired amylase (2,889 +/- 328 units per kilogram per hour) (p < 0.01) and cathepsin B output (7 +/- 3 units per kilogram per hour) (p < 0.01) into the pancreatic juice of rats stimulated by caerulein (control group--serum amylase levels, 6 +/- 1 units per milliliter; pancreatic water content, 74 +/- 1 percent. Furthermore, PBDO with IDH plus ISCH caused the redistribution of lysosomal enzyme from lysosomal fraction (12 kilo times gravity pellet; 40 +/- 3 percent; p < 0.01) to zymogen fraction (1.3 kilo times gravity pellet; 38 +/- 3 percent; p < 0.01) (control group--12 kilo times gravity pellet, 59 +/- 2 percent; 1.3 kilo times gravity pellet, 24 +/- 2 percent) and the impaired pancreatic adenylate energy metabolism (0.79 +/- 0.02, p < 0.02) (control group--energy charge equals 0.88 +/- 0.01). Only PBDO with IDH caused no significant changes. Although only ONO3307 or allopurinol therapy showed the partial significant protective effects against pancreatic injuries, improving serum amylase levels, the administration of ONO3307 in combination therapy with allopurinol showed almost complete protective effects against the pancreatic injuries induced by PBDO with IDH plus ISCH (serum amylase levels, 9 +/- 2 units per milliliter; pancreatic water content, 76 +/- 2 percent; amylase and cathepsin B output, 7,127 +/- 946 and 18 +/- 3 units per kilogram per hour; 1.3 kilo times gravity pellet, 28 +/- 2 percent; 12 kilo times gravity pellet, 54 +/- 2 percent, and energy charge equals 0.85 +/- 0.02).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 8460416 TI - Concurrent audit of early outcome for 1,617 consecutive arterial reconstructions. AB - A concurrent audit of 1,617 consecutive arterial reconstructions performed by one surgeon in three different hospitals is reported. Permanent perioperative neurologic morbidity rate after 766 operations for cerebrovascular disease was 3.1 percent. There was no statistical difference with regard to permanent neurologic morbidity rate among three different hospitals. Perioperative mortality rate for repair of unruptured aortic aneurysms was 5.9 and 46 percent for ruptured aortic aneurysms. Mortality rate of aortofemoral reconstruction and infrainguinal bypass grafting was 4.3 and 2.8 percent, respectively. There was no perioperative extensive amputation after aortofemoral reconstructions. Major amputation was unavoidable in 2.4 percent of the patients undergoing infrainguinal bypass. Physicians performing high-risk procedures should keep concurrent outcome data so the benefits and risks of a procedure can be objectively evaluated. PMID- 8460417 TI - Transhiatal esophagectomy using a ring dissector. AB - Subtotal esophagectomy may be performed without thoracotomy by transhiatal dissection. We describe an alternative to the classical technique of transhiatal manual blunt dissection of the esophagus using a ring dissector, which allows a less traumatic dissection of the esophagus above the carcinoma of the esophagus. This instrument, designed for this particular purpose, produces a rapid and clean blunt dissection. PMID- 8460418 TI - Repeat abdominal access. PMID- 8460419 TI - Conization of cervix uteri with intraoperative adjustment of blade angle. PMID- 8460420 TI - Resection of the caudate lobe through "bloody gultch". AB - Isolated resection of the caudate lobe for primary or metastatic neoplasms is an uncommon operation. Our experience with mobilization of the liver in more than 700 hepatic transplants has led us to a simplified technique for caudate lobe resection. Herein we describe our technique and report our experience with three patients. PMID- 8460421 TI - Surgical treatment for constipation. AB - It is evident that the understanding of the pathophysiology underlying the causes of constipation remains incomplete. In some areas, capacity to identify abnormalities has outstripped the ability to treat them. It is hoped that a continuing effort to gather physiologic data from these patients may result in a coherent, physiologic-based treatment approach with maximum therapeutic benefit. PMID- 8460422 TI - Investigations of the gallbladder pathology associated with dietary exposure to disodium arsenate heptahydrate in juvenile rainbow trout (Oncorhynchus mykiss). AB - Juvenile rainbow trout were fed semi-purified diets with (58 micrograms As/g diet) or without arsenic, added as disodium arsenate heptahydrate (DSA), under standard laboratory conditions for up to 12 weeks, to determine the time-course of development of gallbladder pathology in response to dietary DSA exposure, to correlate this pathology with levels of total arsenic and specific arsenic metabolites in the hepatobiliary system and thereby to attempt to gain some insight regarding the mechanism(s) by which the pathological changes develop. Gallbladder lesions associated with this level of dietary arsenic exposure to juvenile rainbow trout include acute inflammation with oedema of the submucosal tissues and sloughing of the epithelium within the first day of exposure, developing to chronic inflammation with fibrosis of the gallbladder wall. These changes may result from the toxic influence of arsenite absorbed into the epithelial cells. The arsenic content of washed gallbladder tissue is a sensitive indicator of recent dietary DSA exposure, while the chronic inflammatory lesion with extensive fibrosis of the gallbladder wall may provide a longer-term indicator of exposure to toxic levels of DSA in the diet of rainbow trout. PMID- 8460423 TI - Evidence of lipoperoxidation induced by lactic acid on kidney homogenates. AB - Sawas and Gilbert (Arch. Int. Pharmacodyn. Ther., 276 (1985) 301-312) reported that the commercial solution of haloperidol induces lipoperoxidation of kidney homogenates from Sprague-Dawley rats. However, it would appear that this effect is attributable to the excipient, lactic acid, rather than to haloperidol itself. Lactic acid enhances susceptibility to lipoperoxidation of kidney homogenates in a dose- and time-dependent manner by increasing production of thiobarbituric acid reactive substances and slightly decreasing polyunsaturated fatty acids such as arachidonic acid and docosahexaenoic acid. This stimulation of lipoperoxidation may be attributed to a mechanism less dependent on enzymatic action than on Fe2+ and Fe3+. Lactic acid may facilitate iron release and formation of iron complexes, factors which increase susceptibility to oxidative stress. PMID- 8460424 TI - [Hyperparathyroidism--who shall be operated on and who should perform the surgery?]. PMID- 8460425 TI - [Primary hyperparathyroidism. An underdiagnosed disease in Denmark?]. AB - Population-based investigations measuring serum calcium levels seem to indicate a prevalence of primary hyperparathyroidism (pHPT) of 0.4-1% in adults with a figure of about 3% in women over 60 years of age. Annual incidence rate varies and is found to be about 25-30 new cases per 100,000 adults with routine use of serum calcium measurements in diagnostic work-up. In women over 60 years of age the incidence approaches 200 instances per 100,000 individuals. Autopsy studies have demonstrated parathyroid disease in about 10%, one third as solitary adenomas and two thirds as hyperplasia. Annual incidence of surgical interventions, however, is currently found to be low with a frequency of about 2 instances per 100,000 inhabitants in Denmark, but with somewhat higher figures in Sweden and Finland. Recently, the preoperative diagnosis of pHPT has been considerably simplified and requires in most cases solely the demonstration of sustained raised serum calcium levels associated with elevated serum concentration of intact PTH. Investigations indicate that pHPT is underdiagnosed in Denmark, and indications for surgical treatment appear to be restrictive. Compared with Swedish operation series the weight of parathyroid adenomas in Danish series is found to be 3 times higher and the mass of hyperplasia 9 times higher consistent with significantly more elevated serum calcium concentrations. Arguments are presented in favour of an increased interest in diagnosing pHPT and a more liberal approach in the selection of patients for surgical treatment of mild or even asymptomatic disease. Routine measurement of serum calcium concentration in blood samples from patients might be considered in order to increase the incidence rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8460426 TI - [The 24-hour heart rate variability. An important predictor of sudden death after myocardial infarction]. AB - The activity of the cardiac autonomic nervous system can be estimated by measurement of beat to beat variations in heart rate-heart rate variability (HRV). In survivors after myocardial infarction, reduced 24-hour HRV, is an independent predictor of mortality/sudden cardiac death. The attenuated HRV is presumed to indicate reduced vagal function and concomitant high sympathetic activity. In experimental studies, this combination reduces the threshold for inducing malignant tachyarrhythmias, and is very probably a clinically important factor for the evolution of ventricular arrhythmias. Measurement of HRV in ordinary 24-hour ECG recordings can, together with other non-invasive measurements, stratify arrhythmic risk in survivors of myocardial infarction. PMID- 8460427 TI - [Acne vulgaris]. AB - Acne vulgaris is one of the most common dermatological diseases. The prevalence may be as high as 83-95% at age 16, but decreases at age 20, and is very low at age 35. The aetiology and pathogenesis are not completely known, but the following factors are involved: 1) increased sebum secretion, 2) follicular keratinisation, 3) bacteria and 4) inflammation. Furthermore, genetic and exogenic factors play a role. Acne can be divided into 5 groups depending on its severity. Treatment principles within these 5 groups are reviewed. Treatment can not be expected to take effect before 1-2 months have passed, but all patients can be cured with the right treatment. The effects and side effects of the various treatments are described. Treatment with isotretinoin should only be initiated by dermatologists. PMID- 8460428 TI - [The value of bone marrow scintigraphy in patients with recurrent breast cancer]. AB - Attempts were made to assess the value of various methods of demonstration of bone metastases in patients with recurrence of cancer of the breast. A material of 123 patients with suspected or verified recurrence of cancer of the breast was submitted to a programme of investigation consisting of conventional X-ray survey of the axial skeleton and thorax, bone tissue scintigraphy, bone marrow scintigraphy, bone biopsy and aspiration of marrow and blood status including serum alkaline phosphatase. 54% and 29% of the patients had bone, metastases as assessed radiographically and by biopsy, respectively. In patients with radiographically demonstrated bone metastases, the predictive value of positive (PV-pos) whole-body scintigraphy was 79%. The findings on bone tissue scintigraphy and bone marrow scintigraphy were in agreement with the radiographic findings in 78% and 72%, respectively, and with the biopsy findings in 71% and 74%, respectively, of the cases. All of the cases of metastases verified by biopsy were identified also by radiographic examination and by bone tissue scintigraphy. The predictive value of negative bone tissue scintigraphy (PV-neg) was 76% and of bone marrow scintigraphy 65%. With biopsy as the final proof, bone tissue scintigraphy, bone marrow scintigraphy and radiography were found to have PV-pos values of 96%, 89% and 95%, respectively and PV-neg values of approximately 50% for all three forms of examination. Bone marrow scintigraphy has thus no diagnostic advantages as compared with bone tissue scintigraphy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 8460429 TI - [Urinary tract symptoms in relation to pregnancy and labor in primiparas]. PMID- 8460430 TI - [Food intake, depressed appetite and chemosensory threshold in patients with cancer during chemotherapy]. AB - Energy and protein intake and eating-related complaints were studied in 52 patients with cancer of the breast, ovary or lung prior to and after 1 and 3 cycles of chemotherapy. Pretreatment intakes were somewhat lower than recommended, but did not change after therapy. Many patients had eating-related complaints, but these complaints did not increase after therapy. Eating-related complaints (except poor appetite) had no impact on intake. Electrical taste detection thresholds and chemical smell detection thresholds were measured before and after three cycles of chemotherapy. Changes in food intake had no relation to changes in chemosensory thresholds. Perceived taste and smell changes were not reflected in chemosensory thresholds. PMID- 8460431 TI - [A colostomy plug (the Conseal system). Assessment of early postoperative use]. AB - The Conseal plug was evaluated in a four week period among 30 consecutive colostomy patients. The clinical trial, a multicenter study covering 11 Danish Hospitals, was started five to 12 days postoperatively among motivated patients in good physical condition. Twenty patients (67%) completed the trial. Ten patients (33%) gave up because of wound infection, leakage, extrusion of the foam part or fault in the test procedure. At the end of the trial all 20 patients wanted to continue using the plug and 84% were still using the Conseal system six months later. We conclude that the plug is well tolerated among motivated patients less than a week postoperatively and that the Conseal plug is a good alternative to the colostomy bag early in the postoperative course. PMID- 8460432 TI - [Visual acuity testing with visual acuity cards in mentally retarded children and children with motoric handicaps]. PMID- 8460433 TI - [Use of alternative treatment among hospital staff in a psychiatric and a rheumatology department]. AB - Staff members of a psychiatry and a rheumatology department were given a questionnaire concerning their use of alternative treatment. The response rate was 59% (111 of 187). Of 111 replies it was found that 48% had used alternative treatment at least once, while 23% had used alternative treatment within the 3 months preceding the interview. There were no significant differences in the use of alternative treatment in relation to sex or age. Only 22 had paid more than 1000 Dkr. for alternative treatment during their lifetime. The personnel's total expenses for alternative treatment within the last 3 months were 10,400 Dkr. paid by 19 members of the personnel. Compared to investigations of the general population this investigation indicated that the hospital staff had used alternative treatment more widely. Staff use of alternative treatment was at a similar level to that found in different patient group. If the way in which the staff relates to illness and treatment serves as a model for others, it cannot be expected that they counteract the use of alternative treatment. PMID- 8460434 TI - [Sarcoidosis presenting as symptomatic myopathy]. AB - We report the case of a 46-year old man who presented with symptomatic myopathy. Muscle biopsy revealed epithelioid granulomas consistent with sarcoidosis. The patient had no symptoms other than those of muscle involvement. He responded well to a moderate dose of corticosteroid. We discuss the differential diagnosis of this rare illness. PMID- 8460435 TI - [Pleuropulmonary manifestations of rheumatoid arthritis. A casuistic reminder]. AB - A case of pleuropulmonary manifestations of rheumatoid arthritis (RA) in the form of persistent pleuritis and effusion in a 58 year old male patient with known RA is presented. The well-known pleuropulmonary complications of RA pleurisy, interstitial fibrosis, effusion, rheumatoid nodules and Caplan's syndrome can occur in sero-negative patients without primary articular symptoms and therefore pose difficult problems in differential diagnosis. These problems can be partially overcome by thoracoscopic visualization of the often characteristic changes of the parietal pleura: hyperemia, vasculitis and rheumatoid nodules and histochemical examination of the pleural liquid will show low glucose concentration, high protein concentration, elevated lactate-dehydrogenase concentration, acid pH and a characteristic cytomorphology with mononuclear and neutrophil leucocytes in typical cases. The pleuropulmonary manifestations can sometimes be successfully treated with a combination of NSAIDs and methotrexate. PMID- 8460436 TI - [Hyperlipidemia in children]. PMID- 8460437 TI - [Infections and intravenous catheters]. PMID- 8460438 TI - [Treatment of gallstones--lithotripsy, classical, mini or laparoscopic cholecystectomy?]. PMID- 8460439 TI - [Psychosocial factors and breast cancer]. PMID- 8460440 TI - [Psychosocial factors and breast cancer]. PMID- 8460441 TI - [How is cobalamin deficiency diagnosed?]. PMID- 8460442 TI - Metastatic renal cell carcinoma to the bladder. AB - We report a case of metastatic renal cell carcinoma to the bladder. Our patient presented gross hematuria 6 months after treatment of the primary lesion. The possible routes and treatment regimens of metastasis of this site of lesion are discussed and a review of the literature is presented. PMID- 8460443 TI - Urethral carcinosarcoma following total cystectomy for bladder carcinoma. AB - A patient with carcinosarcoma of the urethra occurring 15 years after a radical cystoprostatectomy for transitional cell carcinoma is presented. The tumor arose from the penile urethra and invaded the glans penis and penile corpus cavernosum. The tumor was composed of mixed carcinoma (squamous cell carcinoma, adenocarcinoma and transitional cell carcinoma) and rhabdomyosarcoma. Biopsy of the right inguinal lymph node showed simultaneous metastasis of sarcomatous and transitional cell carcinoma elements. PMID- 8460444 TI - Father-son testicular cancer. AB - Testicular tumors in closely related family members are rare. We report a case of familial testicular cancer occurring in father-son pairs. The father had teratocarcinoma and his son developed pure seminoma. The association of a genetic factor in the etiology of testicular malignancy is discussed. PMID- 8460445 TI - Myelolipoma of the adrenal gland. AB - We report 2 cases of large adrenal myelolipoma. Although their fatty nature was found by a CT scan and there was no endocrine activity, surgery was done because of their size and the caused discomfort. PMID- 8460446 TI - Benign polyp with prostatic-type epithelium in the anterior urethra accompanied with urethral stricture. AB - Benign polyp with prostatic-type epithelium in the anterior urethra is rare. We present a case of the same lesion accompanied with urethral stricture. A literature review and discussion of this rare entity are also presented. PMID- 8460447 TI - Submucosal migration of ureteric calculi: related to ESWL? AB - Three patients were reinspected by ureteroscopy after repeat ESWL. Ureteroscopy initially did not disclose an intraluminal stone and only visualized a severe inflammatory reaction of the ureteric wall and a boss of the ureter at the level of the fluoroscopically suspected stone location. An intact stone in all 3 cases was finally exposed by tactile contact at the top of the ureteroscope after perforating the mucosa with a guide wire. Retrospectively, the combination of long-standing stone impaction together with damage to the ureteric mucosa during shockwave interaction may cause an inflammatory reaction with submucosal migration of the stone. PMID- 8460448 TI - Malleable penile prosthesis removal leaving behind the rear tip extenders: a clinical presentation. AB - Perineal pain and a foreign body in a scout abdominal X-ray are reported as presenting symptoms of a patient who later gave an anamnesis of a penile prosthesis implantation which had become infected and was removed. The foreign bodies turned out to be two rear tip extenders of the prosthesis left behind causing the perineal pain. PMID- 8460449 TI - Cell and tumor markers' immunohistochemistry in transitional cell carcinoma of the bladder. AB - A wide range of cell and tumor markers including the blood group-related isoantigens A, B, O(H) and T-Ag, the cell markers DCA(F36/22) and epithelial membrane antigen (EMA), and the oncogene-related proteins RAP-5p21 and ORP-p21 were investigated by means of immunohistochemistry in selected biopsies from 36 bladder cancer patients with the aim of ascertaining which are of value in patients' survival. A heterogeneous distribution of positivity was found for each marker. In addition, EMA immunostaining correlated significantly (p < 0.05) with patient survival. We conclude that immunohistochemical detection of EMA may provide additional prognostic information in bladder cancer patients. PMID- 8460450 TI - A hydrodynamic model of rabbit corpus cavernosum pressure responses to vasodilators. AB - The intracavernosal pressure changes induced by 3 vasodilating drugs, diazoxide, glyceryltrinitrate and verapamil were investigated during autologous extracorporeal penile blood perfusion in an experimental rabbit model. In order to separate the arterial and venous components the experiments were performed with both intact and interrupted penile arterial inflow. The major hemodynamic effect of these drugs was an increased outflow resistance from the corpora cavernosa, probably effected through relaxation of the corporal smooth muscle. However, the intracorporeal pressure responses only reflected a part of the drug induced smooth muscle relaxation. A theory is presented, according to which the corpora cavernosa are 'accumulating' smooth muscle relaxation, without direct reflection in an increased cavernosal pressure. At the moment when sufficient smooth muscle relaxation is achieved, a sudden increase in cavernosal pressure will appear and lead to an erection. This concept was generated through an approximation of corpora cavernosa to an elastic cylinder following the elastic law of Laplace in combination with the hydrodynamic law of Poiseuilles. PMID- 8460451 TI - Penile venous surgery for cavernosal venous leakage: long-term results and retrospective studies. AB - From February 1987 to September 1991, 122 men with erectile impotence and confirmed cavernosal venous leakage underwent penile venous surgery. After a postoperative follow-up of 36 months, only 18.8% of the patients had satisfactory erections without further therapy. Another 32.5% postoperatively converted to responders to intracavernous injection therapy with vasoactive drugs. Therefore, a total of 51.3% benefitted from the operation. Dynamic pharmacocavernography proved to be the most important examination in terms of establishing indication and prognosis. According to our results, there are two basically different forms of cavernosal venous leakage with different postoperative outcomes: primary and secondary corporeal incompetence. In many cases, an arterial cofactor was determined. PMID- 8460452 TI - Sex-dependent urolithiasis in the portacaval shunt rat. Part I. AB - Stone formation was investigated in 162 male and female Sprague-Dawley rats (96 males and 66 females) following a portacaval shunt and in 58 sham-operated rats which served as controls (31 males and 27 females). 70.8% male and only 7.5% female shunted rats developed urolithiasis. All stones of sufficient size were analyzed. The majority of stones in shunt-operated rats were made of potassium hydrogen urate (23/41), 10 rats had struvite stones without urinary tract infection, the remaining 8 rats had composite stones. Analysis of all stone bearing control animals revealed struvite stones (6/6). Postoperatively, the rats developed polyuria, elevated potassium and uric acid excretion (all sex dependent). Urinary pH levels did not change significantly. Organ changes (atrophy of the liver, the testes and ovaries, hypertrophy of the kidney and the adrenal glands) were significant and differed according to sex. The role of sex hormones and prostaglandins is discussed. PMID- 8460453 TI - Incidence and clinical features of renal tubular acidosis-1 in urolithiasis. AB - To elucidate the frequency and clinical picture of renal tubular acidosis-1 (RTA 1) in nephrolithiasis, the acid-loading test was performed in 474 patients with calcium-containing stones. RTA-1 was detected in a total of 11 patients (6 men and 5 women, 2.3%). The incidence of RTA-1 in female patients tended to be higher than in male patients (3.2 vs. 1.9%). One male patient had the complete form, the others had incomplete form. There was a tendency that RTA-1 patients were younger than non-RTA-1 patients in men, and the former were older than the latter in women. The percentages of positive family history and positive past history were 27 and 45%, respectively. Stones were single in 7 cases and multiple in 4 cases. They were unilateral in 10 cases, and bilateral in 1 case. Hypercalciuria was detected in 2 of the 11 cases, hyperuricosuria was present in none of the 11 cases, and hyperoxaluria in 2 of 8 cases examined. Stones were composed of calcium oxalate in 2 cases, calcium phosphate in 2, and calcium oxalate mixed with calcium phosphate in 3. PMID- 8460454 TI - Treatment of renal stones in a solitary functioning kidney with extracorporeal shock wave lithotripsy. AB - Forty extracorporeal shock wave lithotripsy (ESWL) sessions were performed in the treatment of 36 stones in 22 solitary functioning kidneys between October 1990 and October 1991. We inserted a double-J catheter in all patients preoperatively and no serious obstruction such as stone street formation was observed after treatments. Following ESWL therapy, at the end of 3 months follow-up, 14 patients (63.6%) were completely stone free while in 5 patients ESWL therapy was unsuccessful. ESWL became the treatment of choice for stones in solitary kidneys as a result of its highly effective, safe and encouraging outcome. PMID- 8460455 TI - Self-catheterization after urethrotomy. Prevention of urethral stricture recurrence using clean intermittent self-catheterization. AB - Following urethrotomy approximately 50% develop recurrence within 6 months. Twenty-nine consecutive patients were offered clean intermittent self catheterization (CISC) as a preventive measure against urethral stricture recurrence following internal urethrotomy. Ten patients dropped out during the scheduled 6-month regimen. Of the 19 patients left, a significantly improved flow was maintained over the period of observation. No reoperations were required. Prior to the trial, 14 of the 19 patients had a history of recurrent urethral stricture; 92% of these recurrences were diagnosed within 6 months following urethrotomy. It is concluded that CISC seems to be a promising preventive measure against recurrence of urethral stricture. PMID- 8460456 TI - Nocturnal pollakiuria is a symptom of obstructive sleep apnea. AB - An increased urine excretion has been reported in obstructive sleep apnea (OSA) patients, but it is not clear whether it results in an increased number of nocturnal micturitions. The present study was aimed at investigating the frequency of nocturnal micturitions in OSA patients using a standardized questionnaire prospectively given to 102 OSA patients and 86 healthy male subjects. The frequency of nocturnal micturitions was significantly greater in the OSA patients than in the healthy subjects (more than 70% of the OSA patients with an apnea+hypopnea index > 50 reported nocturnal micturitions more than twice a week versus less than 25% of the healthy subjects, p < 0.0001). The number of nocturnal micturitions was also greater in the OSA patients than in the healthy subjects. There was an effect of age on the frequency of nocturnal micturitions; however, when age-matched subsamples were considered, there was still a significant difference between OSA patients and healthy subjects. In a subgroup of 25 OSA patients reevaluated after at least 1 year of home treatment with nasal continuous positive airway pressure the reported frequency of nocturnal micturitions had significantly decreased (p < 0.001). These results suggest that investigations aimed at establishing a diagnosis of OSA should be part of the work-up of patients complaining of nocturnal pollakiuria. PMID- 8460457 TI - Myocardial ischemia after treatment with methotrexate, etoposide and cisplatin. AB - Cisplatin exerts an additional influence on myocardial ischemia induced by the cardiovascular effects of etoposide. Two cases of myocardial ischemia related to combination chemotherapy with methotrexate, etoposide and cisplatin are reported. While the major toxicity associated with systemic chemotherapy is hematologic, it is suggested that, in elderly patients with increased incidence of atherosclerotic disease, special attention be given to vascular complications of antineoplastic agents. PMID- 8460458 TI - Interventions for wildlife health, conservation and welfare. AB - Environmental changes induced by the activities of the increasing human population are likely, through effects on both hosts and infectious agents, to alter the patterns of incidence of diseases of wildlife. These changes may affect the conservation status or welfare of some populations. There is a need for investigations into causes of wildlife mortality incidents and for assembling information on these to assist in guiding responses to incidents in the future. Increasingly, interventions are made for the conservation or welfare of free living wild animals and veterinary involvement in these ventures is important. PMID- 8460460 TI - Birth of live calves after transfer of frozen-thawed bovine embryos fertilised in vitro. AB - Follicular oocytes were aspirated from bovine ovaries collected at a local abattoir. The cumulus-intact oocytes were matured, fertilised and subsequently cultured in vitro. Of 2297 oocytes exposed to in vitro procedures during a 30-day experimental period, 92 per cent matured, 83 per cent were fertilised, 73 per cent cleaved, 48 per cent developed to the morulae and 14 per cent developed to the expanded blastocyst stage. During this experimental period, 300 similar embryos fertilised in vitro were frozen at different post in vitro block developmental stages. After approximately one year of storage in liquid nitrogen, 98 of these embryos were thawed and cultured either for up to four hours or for two days in tissue culture medium-199. Culturing the embryos for up to four hours was not as successful for in vitro development as culturing for two days. Of the 40 embryos cultured for two days, 67 per cent of early blastocyst stage embryos developed to expanded blastocysts in vitro and 46 per cent of morula stage embryos developed to expanded blastocysts, whereas only 8 per cent of 16-cell stage embryos developed to expanded blastocysts. A 50 per cent pregnancy rate resulted when frozen-thawed embryos were co-cultured for two days before transfer compared with 20 per cent for frozen-thawed embryos cultured for up to four hours before transfer. Five calves were born after a normal gestation period with birthweights ranging from 37.3 to 54.5 kg. PMID- 8460459 TI - Detection of antibodies against Borna disease virus in sera and cerebrospinal fluid of horses in the USA. AB - Sera from 295 horses in the USA were examined by an indirect immunofluorescence assay and Western blot assays to determine the prevalence of Borna disease virus infection. Eight (2.7 per cent) of the samples were positive in both assays, and 18 (6.1 per cent) were positive only in the Western blot assay. The indirect fluorescence titres ranged from 1:20 to 1:80 of antibodies recognising the virus specific antigen from Borna disease virus-infected cells. The purified virus specific proteins isolated from infected rat brains were recognised by positive equine serum samples after immunostaining by a Western blot technique. Information obtained from the owners about the history of the seropositive horses revealed that they were either clinically normal or had a pathological diagnosis of disease unrelated to Borna disease. This is the first report of the detection of antibodies to Borna disease virus in horses in the USA. The disease may be more widespread in a subclinical form, with very long incubation periods, and may not necessarily be restricted to historically endemic areas. PMID- 8460461 TI - Estimating the bodyweight of donkeys. PMID- 8460462 TI - Qualifications in Europe. PMID- 8460463 TI - Canine leishmaniasis. PMID- 8460464 TI - Incontinence in giant schnauzers. PMID- 8460465 TI - Old World screwworm fly (Chrysomyia bezziana) in the Gulf. PMID- 8460467 TI - Veterinary care for ferrets. PMID- 8460466 TI - Prescribing for racehorses. PMID- 8460468 TI - Detection of hog cholera virus antigens in experimentally-infected pigs using an antigen-capture ELISA. AB - An antigen-capture ELISA was used to detect hog cholera virus (HCV) antigens in blood and tissues taken from pigs infected with 2 different strains of virus. Specific antigens were demonstrated in peripheral blood leucocytes (PBLs) and a wide range of tissue samples 4-6 days after infection of pigs with a moderate high virulent HCV strain (Weybridge virus). Strong signal to noise (S/N) ratios were obtained in the ELISA for PBLs and lymphoid tissues such as spleen, tonsil and mesenteric lymph nodes at 5-7 days after infection with the Weybridge virus, S/N ratios varying between 8.1-19.7 for blood samples and 4.3-19.1 for spleen samples. High positive ELISA results were also obtained for duodenum and ileum samples (S/N ratios 10.3-18.6) taken from these pigs, reflecting severe pathological changes observed in the gut at post mortem. In contrast, the antigen capture ELISA gave strong positive results for PBLs and spleen samples only at 7 9 days after infection of pigs with a low virulent strain of HCV (New South Wales virus). The ELISA S/N ratios averaged 9.5 for PBLs and 8.9 for spleen samples in these animals. Although virus isolation detected infection earlier in the infected pigs, the ELISA returned positive results on PBLs and spleen samples around the time all of the animals first showed typical signs of classical swine fever. The technique does not require tissue culture and takes less than 36 h to return a definitive result. PMID- 8460469 TI - The porcine intestinal spirochaetes: identification of new genetic groups. AB - The weakly beta-haemolytic isolates were divided into 56 electrophoretic types (ETs), contained in three distinct genetic groups (A,B and C). Group A corresponded to the genus Serpulina, and could be divided into three divisions. It contained 17 weakly haemolytic isolates in divisions b and c, as well as all 98 isolates of S. hyodysenteriae, located in division a. All seven weakly beta haemolytic isolates that produced indole and had alpha-glucosidase but not alpha galactosidase activity fell into division b. These spirochaetes may represent a distinct species. The other ten weakly beta-haemolytic spirochaetes, in division c, fitted the description of S. innocens. Group B contained 17 of the weakly beta haemolytic isolates (18.9%) in ten ETs. Isolates in this group differed from typical S. innocens in that they lacked alpha-galactosidase activity. Group B represented a distinct group of weekly beta-haemolytic spirochaetes, which may constitute a new genus. Group C contained 56 of the weakly beta-haemolytic isolates (62.2%) located in 29 ETs. The original isolate from "spirochaetal diarrhoea" (P43/6/78-Taylor et al., 1980) was located in this group, together with Australian isolates from a similar condition. Spirochaetes in group C were morphologically distinct from those in groups A and B in that they possessed only four, five or occasionally six, subterminal axial filaments, were more slender, and had more pointed ends to their cells. We consider that group C represents a new genus of spirochaetes, members of which may be associated with spirochaetal diarrhoea. PMID- 8460470 TI - Further characterization of Pasteurella haemolytica-like bacteria isolated from swine enteritis. AB - DNA-DNA hybridization studies were conducted on six Pasteurella haemolytica-like (PHL) organisms recovered from cases of swine enteritis. Chromosomal-enriched fractions of PHL organisms served as the source of DNA for Southern blots or as whole-chromosomal DNA probes. Under stringent hybridization conditions, chromosomal DNA probes of a prototype PHL (strain 6213A) organism distinguished other PHL organisms from Pasteurella haemolytica types A1 and T3, Pasteurella multiocida types A:1 and A:3, Escherichia coli, Pseudomonas aeruginosa, Actinobacillus pleuropneumoniae type 1, and Salmonella cholerasuis. The guanine cytosine content of the DNA of three PHL strains was 41.2 to 42.8 mol % as calculated from the thermal denaturation midpoint temperatures. The PHL strains are Gram-negative, nonmotile, beta-hemolytic, pleomorphic, oxidase-positive, urease- and indole-negative, fermentative rods with the key characteristics of the species Pasteurella haemolytica. None of the PHL strains reacted with the type-specific antisera of P. haemolytica types 1 through 12 as tested by an agglutination procedure. These swine strains differed in their biochemical differentiation from P. haemolytica types A1 and T3 in that all produced acid from M-inositol and failed to grow on MacConkey agar. Acid production from trehalose and L-arabinose was variable with PHL strains. Leukotoxicity of PHL strains was evaluated by a colorimetric micro-titration assay. Sterile culture supernatants of three of five PHL strains were toxic to bovine neutrophils. Results of these studies suggest that the PHL organisms may belong to a new group of organisms under the genus Pasteurella. PMID- 8460471 TI - Mutagenesis of the virion-sense open reading frames of tomato leaf curl geminivirus. AB - A series of frame shift, deletion, and inversion mutants in the virion-sense open reading frames (ORFs) of the monopartite geminivirus tomato leaf curl virus have been constructed and their ability to replicate, produce single-stranded DNA, spread, and cause symptoms in tomato plants has been investigated. Disruptions in the V1 ORF lead to symptomless, systemic infections with a reduced titer of all viral DNA forms while interruptions in the V2 (coat protein) ORF disrupted spread of the virus. Mutagenesis of the virion-sense ORFs did not affect the replication of viral double-stranded DNA, although both V1 and V2 products appear to play a role in the accumulation of viral single-stranded DNA. PMID- 8460472 TI - Transcripts of a maize chlorotic mottle virus cDNA clone replicate in maize protoplasts and infect maize plants. AB - A full-length cDNA clone (pMCM41) was constructed to contain the exact 5' end of MCMV behind a T7 RNA polymerase promoter and a Smal site at the 3' end. Uncapped RNA synthesized from pMCM41 has the exact 3' end of viral RNA (vRNA) but is missing the cap found on vRNA. This RNA was infectious in protoplasts from black Mexican sweet (BMS) maize (Zea mays) suspension cultures. Uncapped transcripts were also infectious when inoculated onto maize plants and produced an infection indistinguishable from vRNA-inoculated plants. Capped pMCM41 transcripts which initiated at position +2 of the cDNA clone, as well as capped or uncapped RNA synthesized from a clone containing an extra G between the T7 promoter and the 5' end of MCMV sequence (pMCM721), were less infectious than uncapped pMCM41 transcripts in BMS protoplasts. The transcripts one nucleotide longer or shorter than uncapped pMCM41 transcripts were not able to infect maize plants. PMID- 8460473 TI - Dolphin and porpoise morbilliviruses are genetically distinct from phocine distemper virus. AB - The morbilliviruses recently isolated from two cetacean species in the North and Mediterranean Seas have been shown to differ from phocine distemper virus isolated from European seals using monoclonal antibodies. We have identified a "universal" morbillivirus primer set, based on highly conserved regions of the morbillivirus phosphoprotein (P) gene and used this to amplify a region surrounding the RNA editing site from all known members of the group. Sequence analysis of this region of the gene shows that the dolphin and porpoise viruses are related but quite different from all other members of the group, forming a distinct lineage more closely related to the ruminant morbilliviruses than to the carnivore viruses. PMID- 8460474 TI - Lambda kil-mediated lysis requires the phage context. AB - The lambda kil gene has been shown to be responsible for premature lysis effected by addition of chloramphenicol between 15 and 20 min after thermal induction of a lambda prophage. Here, we localized the kil reading frame. The kil gene, represented by lambda orf47, overlaps genes cIII and gam. Expression of the plasmid-borne kil gene resulted in growth arrest, a reduction of colony-forming units and filament formation. However, kil-mediated cell lysis could not be triggered by chloramphenicol when the plasmid borne kil gene was expressed, suggesting that kil-induced cell lysis requires the phage context. PMID- 8460475 TI - Folding and assembly of viral membrane proteins. AB - It is now clear that folding in the ER is a dynamic, energy-driven process involving a host of cellular folding enzymes and molecular chaperones (see Fig. 1). Within this high-capacity folding environment, nascent molecules fold quickly and efficiently, while misfolded proteins are recognized and retained, being either degraded or rescued. The quality control mechanisms which account for this selective retention are most likely redundant and general in nature--an almost innumerable number of structures, from both endogenous and exogenous proteins, are operated on with equal efficiency. Studies with viral membrane proteins will continue to help illuminate these processes and have contributed greatly to the concepts of conformational maturation and quality control. Furthermore, while the effects of mutations on protein structure and transport cannot always be predicted, useful generalizations can now be made to help develop experimental strategies. Future studies will have to address a variety of unresolved issues. Given the almost limitless sequence and structural variability exhibited by proteins which fold in the ER, no one molecular chaperone is likely to be able to bind to all folding intermediates. Thus, GRP78-BiP is likely to be only one of a number of resident ER molecular chaperones. Identifying these molecules, the structural features to which they bind, and how they interact with other components of the folding machinery are areas in which important advances can be made. A particularly intriguing problem concerns the mechanisms by which the folding machinery is regulated. The synthesis of GRP78-BiP, for example, is strongly induced by elevated levels of misfolded proteins in the ER. How the levels of misfolded molecules are monitored and how this information can be used to regulate GRP78-synthesis is not known. Likewise, the means by which the ER environment, such as its oxidizing potential, is regulated have yet to be elucidated. It is important to note that a direct role for GRP78-BiP (or any other ER molecular chaperone) in folding has yet to be demonstrated in vitro. Reconstituting complex folding reactions in vitro will provide a way to specifically address the roles of folding enzymes and chaperones in protein folding and assembly. The molecular mechanisms which lead to the retention of misfolded proteins in the ER are still poorly understood, as are the mechanisms which lead to their degradation. Finally, whether quality control mechanisms play significant roles in regulating protein transport in other organelles represents an interesting area of research. PMID- 8460476 TI - Mutational analysis of cis-acting sequences and gene function in RNA3 of cucumber mosaic virus. AB - RNA3 of the Kin strain of the tripartite (+)-strand cucumber mosaic virus has 2199 nucleotide residues. Two open reading frames encoding 3a protein (a putative movement protein) and coat protein (CP) are separated by a 286-nucleotide inter cistronic region (IR). This IR contains a subgenomic promoter for production of a subgenomic RNA (RNA4), from which CP is synthesized. Using transcripts generated from mutant forms of a cDNA clone of RNA3, we have characterized the cis-acting sequences necessary for RNA3 accumulation and RNA4 synthesis and analyzed the role of the RNA3-encoded proteins. Efficient accumulation of RNA3 derivatives in tobacco protoplasts required 92 nucleotides at the 5' end, 250 nucleotides in the IR, and 275 nucleotides at the 3' end of the RNA molecule. The 250-nucleotide IR includes a 90-nucleotide sequence which is necessary for subgenomic promoter activity. Although common regions are involved in RNA3 accumulation and RNA4 synthesis, the modes of action of IR for these two phenomena are different. The analysis of forms of RNA3 with internal duplications demonstrated that RNA3 accumulation depended on the context of the IR. Subgenomic promoter activity was more position dependent and was always stronger from the promoter closer to the 3' end of the (+)-strand RNA. A mutation in IR specifically affected (+)-strand RNA accumulation, indicating a role for that region in (+)-strand synthesis. The role of the RNA3-encoded proteins was analyzed by mutation and inoculation either to plants or to protoplasts. Mutation of the 3a protein had no effect on RNA3 accumulation in protoplasts, whereas CP mutations caused reduced CMV RNA accumulation. This reduction was more pronounced for (+)- than for (-)-strand accumulation. RNA of CP mutations was undetectable in inoculated leaves, whereas RNA of 3a protein mutants accumulated, albeit at levels several orders of magnitude lower than with wild-type CMV. The conclusion from these data is that both proteins are required for efficient spread of CMV from the site of infection. PMID- 8460477 TI - Overexpression of wild-type p53 and c-Myc in human fetal cells transformed with adenovirus early region 1. AB - The expression of p53 in a large panel of adenovirus (Ad) 2/5- and 12-transformed human, rat, and mouse cells has been examined. In all cases, in the absence of the larger Ad E1B protein, the level of p53 is very low. In human and rat cells when the Ad 12 E1B 54K polypeptide is expressed, p53 is much more abundant, although this is not the case in Ad 12 E1-transformed mouse cells. We conclude that expression of p53 is determined by virus serotype, host cell type, and viral proteins expressed. p53 in Ad 12 E1-transformed human cells is wild type but has an extended half-life. Stabilization is not through protein-protein interaction with the Ad E1B protein. The level of expression of c-Myc is also elevated in Ad transformed human cells but this does not correlate with the presence of the E1B protein or with p53. However, Northern blot analysis indicates a direct correlation between mRNA and protein levels. We conclude that c-Myc is regulated at the transcriptional level, whereas p53 is regulated at the post-translational level in adenovirus transformants. PMID- 8460478 TI - Nucleotide sequence and genomic organization of rice tungro spherical virus. AB - Rice tungro disease is caused by a combination of two viruses: rice tungro spherical virus (RTSV) and rice tungro bacilliform virus (Jones et al. (1991) J. Gen. Virol. 72, 757-761.). The genome of RTSV is a single-stranded polyadenylated RNA. We present here the 12,433-nucleotide complete sequence of RTSV genomic RNA and its deduced coding regions. This sequence contains a large open reading frame (ORF) which initiates following a 514-nucleotide 5' leader sequence and is capable of encoding a viral polyprotein of 390.3 kDa. Two viral subgenomic RNAs of ca. 1.2 and 1.4 kb, respectively, were detected in RTSV-infected leaf tissues and mapped by S1 nuclease protection assay. These RNAs were determined to be congruent with the genomic RNA sequence proximal to the 3' terminus and could contain up to two small ORFs in their 5' to 3' orientation. There are at least three capsid protein subunit cistrons near the N-terminus of the large ORF. A computer-aided search of the C-terminal half of the large ORF revealed conserved protein sequence motifs for a viral RNA polymerase, proteinase, and a putative NTP-binding protein. These sequence motifs are arranged in a manner that resembles those of picorna-like viruses. Taken together, these data indicate that RTSV is a distinct type of positive-strand RNA virus. The evolutionary relationships between RTSV and other picorna-like plant viruses are discussed. PMID- 8460479 TI - Enteric adenovirus type 40: expression of E1B proteins in vitro and in vivo. AB - The genes encoding the enteric adenovirus type 40 E1B proteins designated 19K, 55K, and 15K (55K related) have been cloned into the pET3a expression vector and synthesized by in vitro transcription and translation and by in vivo expression after induction in bacteria. The 19K product expressed in bacteria is recognized by anti-peptide sera specific for the C-terminal region of the open reading frame and has the same M(r) as 19K protein immunoprecipitated from virus-infected cells. The 55K protein synthesized in bacteria is insoluble except under extreme denaturing conditions, but after in vitro transcription followed by translation, a polypeptide of the predicted size is obtained. The 15K protein, equivalent to the first 73 and last 29 of the 476-residue 55K protein with an internal deletion of 374 amino acids, is expressed to a high level in bacteria in a soluble form and interacts weakly but specifically with N- and C-terminal anti-peptide sera. The bacterially expressed 15K protein was used to raise antibodies in rabbits. This serum precipitates the 55K protein expressed by in vitro translation, but only the 15K product can be immunoprecipitated from virus-infected cells. The same antiserum, however, detects the 55K protein in infected cells by Western blotting, at a time broadly coinciding with the onset of DNA replication. This is the first identification of Ad40 55K protein in infected cells and confirms that the Ad40 22S mRNA can be utilized in vivo. The question of whether this protein is functional can now be addressed. PMID- 8460480 TI - 3'-terminal nucleotide sequences important for the accumulation of cowpea mosaic virus M-RNA. AB - The location of nucleotide sequences important in determining the extent of cowpea mosaic virus M-RNA accumulation in cowpea protoplasts has been analyzed by deletion mutagenesis of full-length cDNA clones from which infectious transcripts can be produced in vitro. The results suggest that cis-acting sequences which direct replication of M-RNA by B-RNA-encoded products are located within the 5' terminal 524 nucleotides and the 3'-terminal 151 nucleotides. RNA secondary structure predictions for the 3'-terminal 151 nucleotides of both genomic RNAs (Eggen et al. (1989) Virology 173, 456-464) indicate that the terminal nucleotides form a stable secondary structure composed of a Y-shaped stem-loop and a simple A-U-rich stem-loop. The latter structure has been implicated in B RNA replication. We have examined the role of the Y-shaped structure in M-RNA accumulation by site-directed mutagenesis of putative base-pairing combinations in the two minor stems. The results suggest that efficient replication is dependent on the formation of both of these minor stem structures. PMID- 8460481 TI - Characterization of the Moloney murine leukemia virus stem cell-specific repressor binding site. AB - The Moloney murine leukemia virus (M-MuLV) repressor binding site (RBS) mediates cell-type-specific repression in embryonal carcinoma (EC) cells of expression from several different promoters, including the M-MuLV long terminal repeat promoter. Silencing has been shown to depend on an element normally located in the proviral 5' noncoding region and occurs at the DNA level in the absence of retroviral proteins. Using fragments of the RBS region, we now show that the minimal size of the silencer corresponds to M-MuLV nt 147-163 and overlaps with the retroviral primer binding site region by 17 of its 18 bp. A panel of point mutations within the RBS has been examined to yield a consensus RBS sequence which is consistent with the notion that a previously identified nuclear factor (binding factor A) mediates RBS repression. Viral vectors using neomycin, beta galactosidase, and luciferase reporters have been employed to show that RBS mediated repression occurs in EC and embryonal stem, but not in other tested cell types. Repression was observed to occur within 48 hr of infection, prior to when global methylation of proviruses has been reported to occur. Repression also occurred after azacytidine treatment of EC cells, supporting the notion that the RBS functions independently of provirus methylation. However, levels of provirus methylation in selected cells were increased in the presence of a wild-type RBS, and methylation correlated with a secondary stage of virus repression. Thus, the M-MuLV RBS acts directly to control expression in EC cells and also appears to trigger a secondary level of repression which is coincident with provirus methylation. PMID- 8460482 TI - Enrichment of insertional mutants following retrovirus gene trap selection. AB - The present study has investigated the use of gene trap retroviruses as insertional mutagens. A gene trap vector (U3Hygro) was used to target single-copy thymidine kinase (tk) genes, present at different sites in the genome. Cell populations isolated by gene trap selection contained a higher proportion of insertional mutants as compared with nonselected cells containing randomly integrated viruses. The number of integration events required to observe loss of gene function was reduced from 8-40 x 10(6) to 2-10 x 10(4), an overall enrichment of 100- to 1000-fold. The feasibility of targeting normally diploid genes was also demonstrated in hypodiploid Chinese hamster ovary cells. The cellular gene encoding GlcNAc transferase I was disrupted in one wheat germ agglutinin resistant clone selected from a total of 5 x 10(4) gene trap events. The clone was nullizygous for GlcNAc transferase I, indicating that the allele opposite the provirus was lost as a result of preexisting hemizygosity or by loss of heterozygosity. Finally, the total number of genes in the genome that could activate the expression of retrovirus gene traps was estimated at between 2 x 10(4) and 10(5), suggesting that most expressed genes can be mutagenized by gene trap selection. PMID- 8460483 TI - DNA packaging ATPase of bacteriophage T3. AB - A defined in vitro DNA packaging system of phage T3, which is composed of purified proheads and two packaging proteins, the products of genes 18 and 19 (gp18 and gp19, respectively), displayed a DNA-dependent ATPase activity. ATP was hydrolyzed to ADP and Pi. The ATPase activity was stimulated by nonpackageable DNA, such as single-stranded or circular DNA, or RNA (nonpac-ATPase). Among the inhibitors of DNA packaging, actinomycin D specifically inhibited the ATPase activity that was tightly coupled to DNA packaging (pac-ATPase), but did not inhibit the nonpac-ATPase activity. Both activities depended upon a functional packaging complex, but the nonpac-ATPase, once activated, did not require DNA. Unpackageable pUC18 DNA inhibited the pac-ATPase and the phage yield in parallel. Approximately one molecule of ATP was hydrolyzed during the translocation of 1.8 bp of T3 DNA. PMID- 8460484 TI - Characterization of vaccinia surface antigen expressed by recombinant baculovirus. AB - The gene encoding the vaccinia surface antigen (S antigen) was inserted into a baculovirus transfer vector and a recombinant virus was isolated. The S antigen was expressed on the surface of Spodoptera frugiperda cells (Sf cells) infected with the recombinant baculovirus. Recombinant proteins were detected in immunoblotting with anti-vaccinia serum and have the apparent molecular weight of 40 and 50-kDa. The 50-kDa polypeptide was tunicamycin sensitive and was thus glycosylated. The glycosylated 50-kDa polypeptide was also secreted into culture supernatants. Antiserum directed against the expressed S antigen specifically reacted to the authentic S antigen that is located on the mammalian cells infected with vaccinia virus, but did not affect the production of infectious progeny virus. Antisera against both the terminal regions of the S antigen were prepared by immunizing rabbits with the recombinant fusion proteins produced in the bacterial expression vector. The S antigen on the cell surface reacted by immunofluorescence with anti-C-terminus serum but not or very weakly with anti N terminus serum, indicating that the hydrophobic N-terminus functions both as a signal and a membrane anchor sequence. Interleukin (IL)-1 alpha failed to bind to the S antigen expressed on insect and mammalian cells, although the homology between IL-1 receptor and the S antigen has been reported by computer analysis of amino acid sequence. PMID- 8460485 TI - Adenovirus early region 4 and viral DNA synthesis. AB - Mutants of human adenovirus type 5 (Ad5) lacking early region 4 (E4) display a complex phenotype that includes a delay in the onset of viral DNA replication in low-multiplicity infections. Studies of viral DNA replication in vitro have not revealed a requirement for E4 products in DNA synthesis and, for most E4 mutants, defects in DNA replication are not apparent at high multiplicities of infection. The effects of E4 mutations on DNA replication therefore may reflect a role for E4 in the regulation of replication rather than in the process of DNA synthesis. The E4 mutant H5d/1014 carries two deletion mutations that together destroy all E4 open reading frames (ORFs) except ORF 4. Immunoprecipitation measurements of the level of the ORF 4 product confirm that H5d/1014 accumulates the ORF 4 product in somewhat larger amounts than wild-type Ad5. H5d/1014 is profoundly defective in viral DNA replication at a multiplicity of infection (50 PFU/cell) and time (24 hr after infection) that permit mutants lacking all seven E4 products to accumulate approximately normal amounts of DNA. In contrast, H5d/1019, a derivative of H5d/1014 in which the expression of ORF 4 is prevented by a mutation in the ORF 4 ATG initiator codon, produces DNA normally under these conditions. The product of ORF 4 therefore is necessary for the inhibition of viral DNA replication in H5d/1014-infected cells. H5d/1014 also inhibits, in trans, the synthesis of viral DNA by other E4 mutants that lack both E4 ORFs 3 and 6. Viruses that possess either of those ORFs are not subject to inhibition, indicating that the ORF3 and 6 products antagonize the effect of ORF 4. These observations are consistent with a regulatory role for the E4 ORF 3, 4, and 6 products in viral DNA replication in adenovirus-infected cells. PMID- 8460486 TI - Genome structure of a virus infecting the marine brown alga Ectocarpus siliculosus. AB - We describe a procedure for the isolation of virus particles from the marine brown alga Ectocarpus siliculosus. Virus particles are composed of at least 13 different polypeptides, including two glycoproteins, and double-stranded DNA. A typical virus DNA preparation contains three fractions, namely linear DNA and circular DNA, each composed of about 320 kilobase pairs, as well as DNA fragments, 10 to 60 kilobase pairs in size. The large linear and the circular DNA contain single-stranded regions (average length: 2.9 kilobase). We propose that the native Ectocarpus virus genome is a circular DNA molecule whose double strand is interrupted by single-stranded regions. During the preparation procedure, the DNA circles tend to break at the single-stranded sites producing large linear as well as fragmented DNA. PMID- 8460487 TI - Replication of minute virus of mice minigenomes: novel replication elements required for MVM DNA replication. AB - In this report, we describe the replication of minigenomes of minute virus of mice (MVM). We show that the cis-acting sequences required for MVM DNA replication reside in the terminal 140 and 660 nucleotides of the left and right termini, respectively. Minigenomes containing either two right (RR) or two left (LL) termini are replication competent genomes, demonstrating that both termini contain the genetic information necessary for the excision and initiation of DNA replication. Since the efficiency of replication of the RR genome is greater than that of the LL genome, it suggests that the individual terminal sequences are not equivalent in function. In addition to the terminal palindromic sequences required for replication, we show that specific elements found inboard of the right hairpin between nucleotides 4489-4636 (element A) and 4636-4695 (element B) are necessary for the efficient replication of MVM minigenomes. These elements have heretofore not been identified as replication sequences. PMID- 8460488 TI - Interactions of murine gammaherpesvirus 68 with B and T cell lines. AB - Murine gammaherpesvirus is a natural pathogen of wild rodents. We have established that in vivo the virus persists in B lymphocytes in a latent form and therefore has similar biological properties to Epstein-Barr virus and related gamma-I-herpesviruses. In this report we have established a persistent infection in mouse myeloma (B) cells (NSO cell line), but not in mouse thymoma (T) cells (BW 5147 cell line). The virus persists indefinitely in myeloma cells, without any apparent cytopathic effect, but with the production of infectious virus. We demonstrate that ACV abolishes the productive infection, but large numbers of cells harbor the virus in a latent form, as determined by an infectious center assay. Analysis of the viral DNA has shown that during a persistent infection linear virus genomes predominated, with low levels of circular DNA also present. Treatment of cells with ACV results in a significant reduction of linear genomes, but has no effect on the level of circular DNA molecules. These data provide further evidence to support our earlier observations on B cells as the site of latency and provides an in vitro model with which to study the molecular basis of MHV-68 latency/persistence. PMID- 8460489 TI - Characterization of the in vitro system for the synthesis of mRNA from human respiratory syncytial virus. AB - An in vitro transcription system for human respiratory syncytial virus (RSV) is described. Purified viral nucleocapsid (RNP) isolated from virus-infected cells was shown to support transcription of all 10 genes encoded by the virus as determined by Northern blot hybridization. The mRNAs synthesized were polyadenylated and comigrated with the corresponding mRNAs synthesized in virus infected cells when analyzed in agarose-urea gel electrophoresis. The in vitro synthesized mRNAs are functional as determined by their capacity to synthesize protein in vitro. The transcriptional reaction was significantly stimulated by the uninfected host cell lysate, indicating a requirement of host factor(s) in mRNA synthesis. Preliminary results suggest that cellular actin is involved in this process. PMID- 8460490 TI - Phylogenetic analysis of the N8 neuraminidase gene of influenza A viruses. AB - Phylogenetic analysis of the N8 neuraminidase (NA) genes from 18 influenza A viruses, representing equine and avian hosts in different geographic locations, revealed three major lineages: (i) currently circulating equine 2 viruses; (ii) avian viruses isolated in the Eurasian region, including A/Equine/Jilin/1/89, a recent avian-like N8 isolate found in horses in China; and (iii) avian viruses isolated in North America. Comparison of mutation rates indicated that avian N8 genes have evolved more slowly than their equine counterparts. That is, in both avian lineages, 72% of the nucleotide changes were silent in the terminal branches of the phylogenetic tree, whereas in equine 2 viruses, 59% of the nucleotide changes were silent. This suggests greater selective pressure on the NA gene from the mammalian immune system, leading to progressive evolution. Alternatively, the slower mutation rate for avian N8 genes could reflect a selective advantage gained from a longer, continuous span of evolution. The shape of the phylogenetic tree, the evolutionary rate, and the calculated date of origin for the N8 equine 2 virus lineage were comparable to findings for the equine 2 virus hemagglutinin (HA) gene (Bean et al., J. Virol. 66, 1129-1138, 1992). This suggests that both viral membrane glycoproteins of equine 2 viruses have evolved together and have been subjected to similar levels of selective pressure. Several amino acid residues were found to differ among the three host specific lineages, but they may not be involved in host restriction of the NA, as they are shared by EQ/Jilin/1/89 and viruses of avian origin. The present findings complement detailed structural information on the N2 and N9 subtypes and should prove valuable in understanding future X-ray diffraction studies of N8 crystals. PMID- 8460491 TI - Long-term noncytopathic productive infection of the human monocytic leukemia cell line THP-1 by human immunodeficiency virus type 1 (HIV-1IIIB). AB - A long-term, noncytopathic, productive infection of the monocytic leukemia cell line THP-1 with human immunodeficiency virus type 1 (HIV-1IIIB) was established. Both infected cells (THP-1/HIV-1IIIB) growing in suspension and uninfected, phorbol 12-myristate 13-acetate (PMA)-treated THP-1 cells, which are adherent, showed ultrastructural characteristics of differentiated cells. PMA-treated THP-1 cells could not be productively infected with HIV-1IIIB. THP-1/HIV-1IIIB cells produced virions mainly by budding at the plasma membrane. These cells retained the ability to differentiate into macrophage-like cells, capable of releasing the virus for extended periods of time (e.g., 40 days). PMA-mediated differentiation of THP-1/HIV-1IIIB cells modified the pattern of virus localization. Immediately after PMA treatment mature viral particles were primarily observed extracellularly. After 21 days in culture, however, the virions accumulated in intracellular vacuoles. THP-1/HIV-1IIIB cells may be used as a useful model system for HIV-infected macrophages. PMID- 8460492 TI - Dengue 2 virus NS2B and NS3 form a stable complex that can cleave NS3 within the helicase domain. AB - Flavivirus genomic RNA is translated into a large polyprotein that is processed into structural and nonstructural proteins. The N-termini of several nonstructural proteins are produced by cleavage at dibasic sites by a two component viral proteinase consisting of NS2B and NS3. NS3 contains a trypsin like serine proteinase domain at its N-terminus, whereas the function of NS2B in proteolysis is yet to be determined. We have used an NS3-specific antiserum, under nondenaturing conditions, to demonstrate that NS2B and NS3 form a complex both in vitro and in vivo. The N-terminal 184 residues of NS3 are sufficient to form the complex with NS2B. The complex forms efficiently when the NS2B and NS3 are translated from two different mRNAs as well as when NS2B and NS3 are translated as a polyprotein from the same mRNA. A chimeric complex can be formed between yellow fever NS2B and a chimeric yellow fever-dengue 2 NS3. Using anti NS3 antisera, we also found that a 50-kDa fragment of NS3, consisting of the N terminal approximately 460 residues, is produced in infected mammalian cells. This fragment is not produced in infected mosquito cells, but will form in Triton X-100 lysates of mosquito cells. The cleavage of NS3 to form this fragment is catalyzed by the NS3 proteinase itself and proteolysis requires NS2B. Examination of the amino acid sequence of NS3 reveals a potential conserved cleavage site that resembles other sites cleaved by the NS3/NS2B proteinase; this site occurs within a conserved RNA helicase sequence motif. The importance of this alternatively processed form of NS3 and its role in the replication cycle of dengue virus remain to be determined. PMID- 8460493 TI - Genetic analysis of beet curly top virus: evidence for three virion sense genes involved in movement and regulation of single- and double-stranded DNA levels. AB - The monopartite DNA genome of beet curly top geminivirus (BCTV, strain Logan) contains four leftward, complementary sense open reading frames (ORFs) designated L1, L2, L3, and L4 and three rightward, virion sense ORFs designated R1, R2, and R3 (R1 encodes the coat protein). The R3 ORF has not been reported previously in the BCTV genome, and evidence for three functional virion sense genes on one genome component has not been presented before for any geminivirus. We investigated the functions of the virion sense ORFs by introducing mutations into each of them. We found that in Nicotiana benthamiana plants, BCTV genomes containing mutations in ORF R1 were not infectious, whereas an R3- mutant was very weakly infectious. The small proportion of plants infected by the R3- mutant remained asymptomatic and contained greatly reduced amounts of viral DNA. An R2- mutant was highly infectious but asymptomatic, and in infected plants it accumulated mostly the double-stranded DNA (dsDNA) replicative form in nearly wild-type amounts. All of the mutants replicated in tobacco protoplasts, although R1- and R2- mutants accumulated reduced amounts of genomic single-stranded DNA (ssDNA) relative to wild-type virus. In the case of R2- mutants, the reduction was large (approx. ninefold) and was accompanied by a similar increase in dsDNA levels. The results suggest that the R1 and R3 gene products are required for efficient movement of the virus in the infected plant, whereas the R2 gene product may be involved in the regulation of ssDNA vs dsDNA levels. PMID- 8460494 TI - A unique conformation at the carboxyl terminus of the small hepatitis delta antigen revealed by a specific monoclonal antibody. AB - Two forms of the hepatitis delta antigen (HDAg), a small (24 kDa) and a large (27 kDa) one, have different functions in the hepatitis delta virus (HDV) replication cycle. The small HDAg trans-activates RNA replication, while the large one inhibits RNA replication. The lack of the trans-acting activity in the large HDAg, even though it contains the complete sequence of small HDAg, suggests that the large HDAg lacks a certain functional conformation. To test such a possibility, monoclonal antibodies (MAbs) were generated from mice immunized with recombinant baculovirus-expressed small HDAg. As expected, most of the MAbs recognized both small and large HDAg. In addition, one MAb (9E4) was obtained which recognized only the small HDAg, but not the large one, in Western blot and immunoprecipitation analysis, suggesting that it recognized an epitope unique to small HDAg. However, MAb 9E4 detected both forms of HDAg in virus-infected cells by immunofluorescence and reacted with TrpE-large HDAg fusion proteins expressed in Escherichia coli, suggesting that this MAb recognizes a conformation-dependent epitope which is not present in the native large HDAg molecule but is detectable in LHDAg when its conformation is altered. The 9E4 epitope was mapped within a region of 32 amino acids at the carboxyl-terminus of small HDAg, indicating that this region contains a unique conformation not present in the native molecule of large HDAg. Since this is the only structure identified that is unique to small HDAg, the C-terminal region may contain the domain associated with the biological activities unique to the small HDAg. PMID- 8460495 TI - Symptomatology and movement of a cucumber necrosis virus mutant lacking the coat protein protruding domain. AB - A cucumber necrosis virus (CNV) mutant which lacks the coding sequence for the coat protein protruding domain, PD(-), was constructed by site-directed mutagenesis of an infectious CNV cDNA clone, pK2/M5 (wild-type, 4701 nt). Transcripts of PD(-) were infectious on Nicotiana clevelandii; however, local lesions produced were significantly smaller than those on the corresponding leaves of plants inoculated with wild-type transcript. In addition, systemic symptoms took 8 to 12 days longer to develop than in wild-type-inoculated plants. The distinctive PD(-) phenotype was lost when N. clevelandii was inoculated with sap from systemically infected leaves of PD(-) transcript-inoculated plants and was replaced by symptoms that were the same as those with wild-type infections. High-molecular-weight RNA from mutant- and wild-type-infected plants was extracted and analyzed by Northern blotting. Full-length PD(-) RNA could be detected only rarely in RNA preparations from transcript-inoculated leaves; a further deleted, stable RNA species of approximately 3800 nucleotides was found in preparations from systemically infected leaves of PD(-) transcript- and sap inoculated plants. CNV coat protein could not be detected by ELISA or ISEM in PD( )-infected leaf material. The ca. 3.8-kb RNA, when cloned and sequenced, was found to have lost all but 74 of the 1140 nucleotides of the CNV coat protein open reading frame. Transcripts from this coat proteinless CNV cDNA clone produced wild-type symptoms on N. clevelandii. It would appear that CNV is able to replicate and move systemically, in both transcript-inoculated and sap inoculated N. clevelandii, in the absence of a functional coat protein. Additionally, mechanical transmission of this virus occurs in the absence of the coat protein; however, such transmission is less efficient when compared with wild-type infections. PMID- 8460496 TI - Nuclear transport of tobacco etch potyviral RNA-dependent RNA polymerase is highly sensitive to sequence alterations. AB - The putative RNA-dependent RNA polymerase (NIb protein) of tobacco etch potyvirus accumulates primarily in the nucleus of infected cells, although viral RNA replication is suggested to occur in the cytoplasm. To understand the possible relationship between NIb nuclear localization and its function, we have studied translocation of NIb using gene fusion and plant transformation techniques. When expressed as a fusion with a cytoplasmic reporter protein, beta-glucuronidase (GUS), NIb efficiently directed transport to the nucleus in transgenic tobacco plants, confirming that NIb contains an independent nuclear translocation signal. The effects of site-directed substitutions and deletions in NIb were analyzed. Substitutions were targeted to three small clusters of basic amino acids that bear some resemblance to well-characterized nuclear localization signals (NLSs) of other karyophilic proteins. Amino acid changes affecting two clusters, between residues 3-5 and residues 303-306, abolished transport activity. However, the assignment of NLS function to these regions was complicated by the fact that substitutions at four additional sites throughout the NIb sequence also rendered the fusion protein primarily cytoplasmic. Each of six deletions in NIb debilitated nuclear localization, regardless of whether the basic clusters were deleted. Insertions of Pro-Pro dipeptides, which were predicted to induce protein folding aberrations, at three out of four positions in NIb reduced translocation. Taken together, these results suggest that nuclear localization activity of NIb may require a stringent tertiary structure in addition to one or more NLSs. PMID- 8460497 TI - Architecture of physalis mottle tymovirus as probed by monoclonal antibodies and cross-linking studies. AB - Physalis mottle tymovirus (previously named belladonna mottle virus, Iowa strain) RNA was cross-linked to its coat protein by exposure of the intact virus to ultraviolet light. The site of cross-linking of the coat protein with the RNA was identified as Lys-10 by sequencing the oligonucleotide-linked tryptic peptide obtained upon HPLC separation subsequent to enzymatic digestion of the cross linked and dissociated virus. Three monoclonal antibodies PA3B2, PB5G9, and PF12C9, obtained using denatured coat protein as antigen, cross-reacted effectively with the intact virus indicating that the epitopes recognized by these monoclonals are on the surface of the virus. Using the peptides generated by digestion with CNBr, clostripain, V-8 protease, or trypsin and a recombinant protein lacking the N-terminal 21 residues expressed from a cDNA clone, it was shown that PA3B2 recognizes the sequence 22-36 on the coat protein while PB5G9 and PF12C9 recognize region 75-110. These results suggest that Lys-10 is one of the specific sites through which the RNA interacts in the intact virus. The polypeptide segment (region 22-36) following this buried portion as well as the epitope within the region 75-110 are exposed in the intact virus. These observations are consistent with the canonical beta-barrel structure observed in certain other plant viruses. PMID- 8460498 TI - A novel mutation within the kinase domain of v-abl gene responsible for temperature-sensitive colony-forming ability in soft agar. AB - Mutation sites of unique temperature-sensitive (ts) mutants of Abelson murine leukemia virus(A-MuLV) that exhibited the ts phenotype in colony-forming ability in soft agar, but not in morphological transformation, were determined. Cloning and sequencing analysis of the full viral genomes of five independent ts mutants revealed a total of 10 mutation sites: 3 mutations (bp714, 742, and 817) located in the 5' untranslated region between LTR and gag gene; 4 mutations (bp1227, 1229, 1512, and 1634) in the gag gene; 3 mutations (point mutations at bp2764 and 3265, and 2-base deletion of bp3448 and 3449) in the abl gene. To determine the mutation sites critical for the ts phenotype in colony-forming ability in soft agar, hybrid viruses were constructed by exchanging the corresponding restriction fragments between wild-type and ts A-MuLV. The hybrid virus containing only the point mutation (T-->G) at bp2764 that exchanged leucine with arginine exhibited the ts phenotype in colony-forming ability in soft agar. Thus, a novel mutation within the kinase domain of the abl gene critical for the ts phenotype in colony forming ability in soft agar was determined here. PMID- 8460499 TI - Specificity of satellite activation by tobacco necrosis virus correlates with nucleic acid hybridization pattern between helper virus isolates. AB - Tobacco necrosis virus (TNV) comprises over 20 different isolates which are usually classified on the basis of serological cross-reactivity of their virus particles or specific activation of satellite virus strains (STNV-1, -2, and -C). We have studied the relationships between five TNV isolates, TNV-A, -G, -CN, -D, and -AC36 which exhibit considerable differences in symptom formation on Phaseolus vulgaris. It is shown that, like TNV-A, TNV-G and -CN support the multiplication of STNV-1 and -2. The ability to activate STNV-1 and -2 is not completely correlated with the virulence of the TNV isolates on Phaseolus as TNV CN infects Phaseolus very inefficiently. The RNAs of all STNV-1 and -2 supporting TNV isolates were detectable by Northern blot analysis using RNA probes derived from TNV-A, whereas the RNAs of the STNV-C activating isolates (TNV-D and -AC36) were only detected with a TNV-D-derived RNA probe. This indicates that the classification of the TNV isolates on the basis of satellite activation is representative of the evolutionary relationships between the isolates. PMID- 8460500 TI - Identification of a region in the Pr55gag-polyprotein essential for HIV-1 particle formation. AB - The pr55gag polyprotein of HIV-1 plays a critical role in the formation of immature virus particles in the cell and during the budding process. We investigated the influence of amino acid substitutions in the p24CA- region of the gag polyprotein on the viral assembly process. Deletion of the amino acids 341-352 in the carboxy terminal part of the p24CA resulted in a loss of the capacity of the gag polyprotein to form virus-like particles when expressed in eucaryotic cells by recombinant vaccinia virus. In further experiments it turned out that the amino acids 341-346 and 350-352 are important for the ability of the pr55gag to form virus-like particles. Because these stretches are conserved among HIV-1, HIV-2, SIV, and FIV, we conclude that these amino acids form a domain highly important for the assembly of these lentiviruses. PMID- 8460501 TI - Primary structure of the canine adenovirus PVII protein: functional implications. AB - The DNA sequence of an open reading frame (ORF) corresponding to the canine adenovirus type 1 (Can 1, Utrecht strain) pro-VII (PVII) protein gene was determined. 560 base pairs were sequenced from the upstream end of the HindIII-A genomic fragment. The sequence gives the 33 C-terminal residues of the penton base protein followed by the 132 residue PVII protein, thus conforming to the same order and location of these genes as in Ad2. The authenticity of this putative PVII-ORF was confirmed by N-terminal sequencing of the cleavage product VII isolated from Can1 virions and also by PCR analysis of Can1 DNA from infected cells and from virions. In addition, the sizes of PVII and VII obtained from translation of the sequence and the proteins observed on the gels were also in agreement. The PVII proteins of Can1 and Ad2 share 57% sequence homology, particularly near the N-terminal third of the molecule, including conservation of the consensus proteinase cleavage site at residue 23. The PVII protein has a predicted MW of 14,626 Da, and an pI of 12.48. Though data bank searches for homology were negative, these viral proteins have significant functional and sequence analogy with histone H3. PMID- 8460502 TI - Productive infection of continuous lines of channel catfish leukocytes by channel catfish virus. AB - Channel catfish virus (CCV) undergoes extensive replication in fingerling catfish and establishes latent infection in survivors. Although the site of viral latency in carriers is unknown, a variety of tissues, including leukocytes, have been implicated. To explore the interaction of CCV and leukocytes further, we examined in vitro infection of continuous lines of cloned catfish B cells and non-cloned lines containing predominantly macrophages and putative T-cells. Our results indicate that all three leukocyte subpopulations were productively infected with CCV, but that the kinetics of infection and the final yields differed markedly. These findings shed light on CCV-leukocyte interaction and suggest that CCV infected autologous macrophage or T-cell lines might be suitable targets for assays of catfish cytotoxic T cell activity. PMID- 8460503 TI - Expression of the La Crosse M segment proteins in a recombinant vaccinia expression system mediates pH-dependent cellular fusion. AB - To study the expression of La Crosse virus (LAC) glycoproteins, G1 and G2, we constructed a cDNA copy of the open reading frame (ORF) of the middle RNA segment and expressed it in a recombinant vaccinia virus (VV.ORF). Cells infected with VV.ORF expressed G1 and G2 at the cell surface and formed syncytia with a pH profile similar to that of LAC. These experiments provide a system of studying the biological functions of the LAC glycoproteins, including processing, targeting, fusion, receptor binding, and antigenicity. PMID- 8460504 TI - The role of the amino terminus of F1 of the Newcastle disease virus fusion protein in cleavage and fusion. AB - Phenylalanine is the amino acid at the amino terminus of the F1 protein of all paramyxovirus fusion proteins with the exception of the avirulent strains of Newcastle disease virus, which have a leucine residue in this position (Toyoda et al. (1989) Virology 169, 273-282). To explore the role of this phenylalanine in the fusion activity of the protein, this residue, amino acid 117 in the fusion protein sequence, was changed to leucine (F117L) or to glycine (F117G) by site specific mutagenesis while maintaining the cleavage site sequence of virulent strains of NDV. While both wild-type and the F117G protein were proteolytically cleaved and F1 was detected, the F117L protein was not cleaved. In the presence of the HN protein, both wild-type F and F117G proteins stimulated fusion, but the F117L protein was inactive in fusion. However, incubation in trypsin activated the fusion activity of the protein. Thus the phenylalanine at the amino terminus of the F1 component of the fusion protein is not required for the fusion activity of the protein. The presence of a leucine at this position blocks cleavage even though the cleavage site sequence is unchanged. PMID- 8460505 TI - Health promotion and disease prevention: United States, 1990. PMID- 8460506 TI - Neurosurgical management of the acquired immunodeficiency syndrome. An update. AB - A retrospective review of a 24-month experience on the neurosurgical service at a large metropolitan hospital identified 33 patients with the acquired immunodeficiency syndrome (AIDS) who underwent diagnostic or therapeutic procedures. Intracranial mass lesions unresponsive to empiric medical therapy for presumed Toxoplasma gondii encephalitis underwent diagnostic biopsy in 22 patients: primary lymphoma was identified in 10 (45%) of these patients, and biopsy led to a treatable diagnosis in 16 of the 22. Patients with lymphoma were significantly more likely to have a single mass lesion than those with other diagnoses. The remaining 11 patients had a wide variety of neurologic disorders, including multiple strokes and transverse myelitis, aspergillous fungal infection of the base of the skull, primary lymphoma of the spinal cord, cat-scratch fever of the spine causing painful radiculopathy, hydrocephalus associated with cryptococcal meningitis, and progressive inflammatory peripheral neuropathy. Two patients had lymphoma within the subarachnoid space. Three patients with well controlled AIDS underwent elective neurosurgical therapy for intractable radiculopathies due to herniated lumbar discs in 2 and cervical spondylosis in 1. Current treatment strategies in AIDS appear to have limited the need for brain biopsy, but the spectrum of neurologic disorders has broadened, requiring continued participation by neurologists and neurosurgeons. With improved long term survival, the elective treatment of non-AIDS-related neurologic disorders in selected patients may be appropriate. PMID- 8460507 TI - Suggested guidelines for rating cardiac disability in workers' compensation. Medical and Chiropractic Advisory Committee to the Administrative Director of the California Division of Industrial Accidents. AB - Cardiac disability ratings in workers' compensation cases currently lack any consistent scientific basis, with varying medical evidence used by different examiners in the same case. Opinions about the extent of disability may differ with the same patient, delaying resolution and the delivery of benefits. We describe guidelines for determining cardiac impairment and suggest a schedule for rating disability based on evidence. Our experience is in California, but arriving at equitable ratings for disability purposes is a nationwide challenge. Exercise stress testing provides the best reproducible data to test the heart's ability to do work. When exercise stress testing is not possible or adequate, alternative or supplemental testing is necessary. Certain conditions, such as hypertension, arrhythmias, coronary artery spasm, and a history of coronary artery operations or myocardial infarction, may affect "cardiac disability" but may not necessarily be reflected in exercise testing. PMID- 8460508 TI - Listening and talking to patients. A remedy for malpractice suits? AB - This study evaluates the hypothesis that the way physicians communicate with patients and the degree patients perceive physician fault for bad medical outcomes are risk factors for the initiation of malpractice lawsuits. The study involved 160 adults who viewed a videotape of a physician treating a patient while using either positive or negative communication behaviors. Participants were told that the case had either a positive result, a bad result through no fault of the physician, a bad result for uncertain reasons, or a bad result that was the physician's fault. Participants then rated their litigious feelings. Results showed that the use of negative communication behaviors by the physician increased litigious intentions. An increased perception of physician fault for the bad result also increased litigious intentions. Uncertainty as to the reason for the bad outcome, however, raised litigious feelings nearly as much as did perceived physician fault. The results of the study support the hypothesis that altering the way physicians communicate and improving patient education can affect the risk of malpractice lawsuits. PMID- 8460509 TI - Cancer genes. AB - Cancer is a genetic disease; tumor cells differ from their normal progenitors by genetic alterations that affect growth-regulatory genes. There exist 2 classes of such cancer genes: the oncogenes, which function as positive growth regulators, and the tumor suppressor genes, which function as negative growth regulators. Oncogenes are widely conserved among diverse forms of life and are active in transmitting growth signals from the cell periphery to the cell nucleus. These signaling functions can be disturbed by many types of genetic change; the result of an altered growth signal is often cancer. Tumor suppressor genes have an attenuating effect on cell growth that is lost as a result of inactivating mutations or deletion of the gene; in DNA virus-transformed cells, it is abrogated by neutralization of the tumor suppressor protein through a viral gene product. Tumor suppressor genes were first recognized in inherited cancers; defects in a tumor suppressor transmitted through the germ line can lead to increased tumor incidence in the offspring. Tumor suppressors also play important roles in nonheritable cancer, however; many tumors in humans show defects in tumor suppressor genes. Most cancers harbor multiple genetic changes in oncogenes as well as tumor suppressor genes. Oncogenes induce aberrant growth through a gain in function; tumor suppressor genes contribute to oncogenesis through a loss of function. Both types of mutation work together to produce cancer; the changes are not constant but increase in number as the tumor develops from benign to more and more malignant. Cancer results from the accumulation of genetic changes. Oncogenes and tumor suppressor genes provide important insights into the regulation of cell growth. This knowledge can now be used to develop gene specific therapies for cancer. PMID- 8460512 TI - Human prion diseases. AB - The Council on Scientific Affairs of the California Medical Association presents the following inventory of items of progress in pathology. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome, and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, and scholars to stay abreast of these items of progress in pathology that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another. The items of progress listed below were selected by the Advisory Panel to the Section on Pathology of the California Medical Association, and the summaries were prepared under its direction. PMID- 8460513 TI - Acquired immunodeficiency syndrome vaccines. PMID- 8460511 TI - Long-range safety and protective benefits of angiotensin-converting enzyme inhibitors for hypertension. Do we need more clinical trials? AB - Inhibition of the renin-angiotensin system is being applied with considerable success to the treatment of hypertension and heart failure. Angiotensin converting enzyme (ACE) inhibitors are the only currently available agents that can achieve this objective. In general, the major therapeutic effects of these agents in the treatment of mild to moderate hypertension or of heart failure are exerted on the vascular tissue through inhibition of the renin-angiotensin system and, secondarily, of the sympathetic nervous system. When cardiovascular functional reserve is diminished and autoregulation of regional and systemic blood flow is strained, however, ACE inhibitors may affect other organ functions (heart, kidneys, and possibly brain), hormones other than the renin system, and local tissue humoral systems. The interrelations between the renin-angiotensin system and several other vasoactive systems--including circulating and locally generated tissue hormones and centrally acting neurohormonal factors--are complex and unclear. A better understanding of these mechanisms and interrelations would allow for a more rational therapeutic use of these agents. Unknown also are the clinical effects of prolonged ACE inhibition. Whether the use of ACE inhibitors can provide primary cardiorenal protection requires proof through definitive clinical trials. PMID- 8460510 TI - Pathobiology of the stratum corneum. AB - The epidermis is a dynamic system whose metabolic activity is regulated in large part by the integrity of the permeability barrier. This barrier resides in the stratum corneum and comprises a unique 2-compartment system of structural protein enriched corneocytes embedded in a lipid-enriched intercellular matrix. Lipid extraction or metabolic imbalances, such as essential fatty acid deficiency, produce barrier abnormalities that in turn result in epidermal hyperproliferation, scaling, and inflammation. When the barrier remains intact, lipid imbalances, such as an abnormal cholesterol sulfate:cholesterol ratio in recessive X-linked ichthyosis, can lead to abnormal corneocyte adhesion (visible scale). Both cellular and intercellular proteins also participate in normal desquamation, and protein abnormalities may provoke abnormal scaling (such as filaggrin in ichthyosis vulgaris). Thus, perturbations of the stratum corneum may be the catalyst for a number of skin diseases, rather than the end result of processes that are initiated in subjacent skin layers. PMID- 8460514 TI - Laboratory evaluation of inherited thrombotic disorders. PMID- 8460515 TI - Enhancing antibody and its role in acquired immunodeficiency syndrome. PMID- 8460516 TI - Iron deficiency. PMID- 8460517 TI - Molecular techniques. PMID- 8460518 TI - Eosinophilic meningitis associated with coccidioidomycosis. PMID- 8460519 TI - Successful medical treatment of an infected prosthetic aortic graft. PMID- 8460520 TI - AIDS--science, medicine, and metaphor. PMID- 8460521 TI - Overwhelming postsplenectomy infection. PMID- 8460522 TI - Overwhelming postsplenectomy infection. PMID- 8460523 TI - Riding, colliding, criminalizing-safety and motorcycle helmet laws. PMID- 8460524 TI - Comparisons of nucleotide and deduced amino acid sequences of the glycoprotein genes of a Chinese street strain (CGX89-1) and a Chinese vaccine strain (3aG) of rabies virus. AB - We analyzed the glycoprotein gene sequences of a Chinese street rabies virus strain (CGX89-1) and a Chinese human rabies vaccine strain (3aG). The complete glycoprotein gene sequence of each strain has 1575 nucleotides and encodes a polypeptide of 524 amino acids. The overall nucleotide homology of these glycoprotein genes is 84.5%, and the deduced amino acid homology is 89.5%. Twenty one percent of the base changes result in amino acid substitutions. Comparison of the homologies of the glycoprotein genes showed that the most conserved region is the ectodomain, whereas the most variable regions are the transmembrane and cytoplasmic domains. The overall nucleotide homologies of the 3aG glycoprotein and the CGX89-1 glycoprotein compared with the Pasteur virus glycoprotein are 91.2% and 84.1% respectively. The glycoprotein gene sequences presented here, the first from isolates of Chinese origin, provide insights into the biologically significant regions of this rabies gene. PMID- 8460525 TI - Tumor necrosis factor-alpha induces circular forms of human immunodeficiency virus type-1 DNA in the persistently infected low-level expressing cell line, ACH 2. AB - The low human immunodeficiency virus type-1 (HIV-1) expressing T-cell line, ACH 2, was used to investigate accumulation of the circular, extrachromosomal form of HIV DNA (HD) after tumor necrosis factor-alpha (TNF-alpha) induction. We chose the 2 long terminal repeat (LTR) circular form to analyze unintegrated HD by polymerase chain reaction (PCR), using primer pairs which flank the 2 LTR HD. Approximately a 10-fold increase in 2 LTR HD was detected intracellularly in the TNF-alpha-induced ACH-2 cells using an end point-dilution assay. To examine the cellular compartment location of the 2 LTR HD accumulation, ACH-2 cells were fractionated into cytoplasmic and nuclear components and further subjected to PCR. A 4- to 5-fold increase in the 2 LTR HD signal was observed in the nuclear fraction. These results indicate that unintegrated HD increases in a chronically infected cell line after TNF-alpha induction. This phenomenon, which previously had been observed only with acute infections, may offer insight into basic pathogenic mechanisms. PMID- 8460526 TI - Toscana virus genomic L segment: molecular cloning, coding strategy and amino acid sequence in comparison with other negative strand RNA viruses. AB - The complete nucleotide sequence of Toscana (TOS) virus (Bunyaviridae, Phlebovirus) L segment was determined. The L segment is 6404 nucleotides long, containing a single open reading frame (ORF) in the viral complementary sense coding for a protein of 2095 amino acids that, as in the case of negative strand RNA viruses, could be part of the RNA polymerase of TOS virus. This ORF is expressed by a messenger RNA (mRNA) as long as the genomic segment. Like the mRNAs expressed by the genomic segments of the other Bunyaviruses, the L mRNA has non-templated sequences at the 5' end. The comparison of TOS L protein sequence with the corresponding sequences of other negative strand RNA viruses showed a very high homology only with the Rift Valley Fever (RVF) virus. The residues conserved between the two proteins are mainly concentrated in the central region and contain three DD motifs proposed by Argos (1988) to be functional domains of DNA and RNA polymerases. The complete sequence of the Toscana virus L genomic segment has been deposited in the EMBL library with the accession number X68414. PMID- 8460527 TI - A H1 hemagglutinin of a human influenza A virus with a carbohydrate-modulated receptor binding site and an unusual cleavage site. AB - Two receptor binding variants of the influenza virus A/Tubingen/12/85 (H1N1) were separated by their different plaque formation in MDCK cells. Hemagglutination of variant I was restricted to red blood cells of guinea pigs, whereas variant II also hemagglutinated chicken cells. The variants differed also in their ability to bind to alpha 2,6-linked sialic acid. Evidence is presented that this difference is determined by a complex carbohydrate side chain at asparagine131 near the receptor binding site which is absent in variant II. With both variants, the arginine found at the cleavage site of all other human isolates analyzed so far was replaced by lysine. PMID- 8460528 TI - Putative full-length clones of the genomic DNA segments of subterranean clover stunt virus and identification of the segment coding for the viral coat protein. AB - Subterranean clover stunt disease is an economically important aphid-borne virus disease affecting certain pasture and grain legumes in Australia. The virus associated with the disease, subterranean clover stunt virus (SCSV), was previously found to be representative of a new type of single-stranded DNA virus. Analysis of the virion DNA and restriction mapping of double-stranded cDNA synthesized from virion DNA suggested that SCSV has a segmented genome composed of 3 or 4 different species of circular ssDNA each of about 850-880 nucleotides. To further investigate the complexity of the SCSV genome, we have isolated the replicative form DNA from infected pea and from it prepared putative full-length clones representing the SCSV genome segments. Analysis of these clones by restriction mapping indicated that clones representing at least 4 distinct genomic segments were obtained. This method is thus suitable for generating an extensive genomic library of novel ssDNA viruses containing multiple genome segments such as SCSV and banana bunchy top virus. The N-terminal amino acid sequence and amino acid composition of the coat protein of SCSV were determined. Comparison of the amino acid sequence with partial DNA sequence data, and the distinctly different restriction maps obtained for the full-length clones suggested that only one of these clones contained the coat protein gene. The results confirmed that SCSV has a functionally divided genome composed of several distinct ssDNA circles each of about 1 kb. PMID- 8460529 TI - Complex formation determines the activity of ribozymes directed against potato virus YN genomic RNA sequences. AB - A ribozyme was synthesized against a conserved region in the RNA-dependent RNA polymerase encoding cistron of the important plant pathogen potato virus Y (PVY). This ribozyme was shown to cleave PVY-specific RNA-transcripts efficiently in vitro, with up to 95% of the substrate RNA being cleaved within 2 h incubation at 37 degrees C. A second ribozyme, designed with much shorter viral complementary arms in an attempt to optimize the efficiency of the cleavage reaction, surprisingly failed to cleave the substrates previously cleaved by the longer ribozyme. A much shorter PVY specific RNA-transcript of only 37 nucleotides (nt), however, was cleaved by this short ribozyme proving its ribozymic activity and indicating that the cleavage activity of the ribozyme is, in part, determined by the substrate involved. Analysis of cleavage reactions on non-denaturing polyacrylamide (PAA) gels indicated that incorrect basepairing, interfering with correct formation of the hammerhead structure, was likely to be responsible for the absence of detectable cleavage of the larger substrates by the short ribozyme. PMID- 8460530 TI - Infantile cerebello-optic atrophy. Neuropathology of the progressive encephalopathy syndrome with edema, hypsarrhythmia and optic atrophy (the PEHO syndrome). AB - Uniform neuropathological changes are described in eight cases of the progressive encephalopathy syndrome with edema, hypsarrhythmia and optic atrophy (PEHO syndrome). Two of the autopsied patients were sisters and two other cases were familial. Macroscopically, cerebral and pronounced cerebellar atrophy was seen, the essential histopathological lesions being confined to the cerebellar cortex and the optic nerve. There was a severe neuronal loss in the inner granular layer of the cerebellum. The Purkinje cells were relatively preserved in number although reduced in size, deformed and slightly disaligned. Their dendrites were horizontally oriented and the proximal axons contained abundant torpedoes. The molecular layer was narrow. The optic nerves were atrophic. Serial neuroimaging studies showed that the disease process is operative during the postnatal period, although a prenatal onset cannot be excluded. An aberrant expression of immunoreactivity against the 200-kDa neurofilament polypeptide in Purkinje cell perikarya indicated disorganization of the cytoskeleton of these cells. The combination of clinical and pathological features of our patients differs from that observed in the few published cases of so-called primary degeneration of the granular layer. Infantile cerebello-optic atrophy, clinically characterized by seizures, blindness and early arrest in psychomotor development, thus seems to constitute a new autosomal recessive disorder. PMID- 8460531 TI - Dystrophin-related protein in skeletal muscles in neuromuscular disorders: immunohistochemical study. AB - Thirty-four biopsied muscles of Duchenne, Becker and congenital muscular dystrophy, congenital myotonic dystrophy and amyotrophic lateral sclerosis were examined by an immunocytochemical method with an anti-dystrophin-related protein (DRP) antibody. Strongly positive immunoreaction to DRP at the neuromuscular junctions in all biopsied specimens and faint reaction on the surface membrane of atrophic fibers in amyotrophic lateral sclerosis suggest that DRP is an anchor protein of the acetylcholine receptor. Additionally, the surface membrane of muscle fibers of Duchenne muscular dystrophy was positively stained. DRP is, therefore, thought to be expressed to compensate for dystrophin deficiency in these muscle fibers.